{"id":"0","document_id":"6794356","passages":[{"id":"1","type":"title","text":["Tricuspid valve regurgitation and lithium carbonate toxicity in a newborn infant."],"offsets":[[0,81]]},{"id":"2","type":"abstract","text":["A newborn with massive tricuspid regurgitation, atrial flutter, congestive heart failure, and a high serum lithium level is described. This is the first patient to initially manifest tricuspid regurgitation and atrial flutter, and the 11th described patient with cardiac disease among infants exposed to lithium compounds in the first trimester of pregnancy. Sixty-three percent of these infants had tricuspid valve involvement. Lithium carbonate may be a factor in the increasing incidence of congenital heart disease when taken during early pregnancy. It also causes neurologic depression, cyanosis, and cardiac arrhythmia when consumed prior to delivery."],"offsets":[[82,739]]}],"entities":[{"id":"3","type":"Disease","text":["Tricuspid valve regurgitation"],"offsets":[[0,29]],"normalized":[{"db_name":"MESH","db_id":"D014262"}]},{"id":"4","type":"Chemical","text":["lithium carbonate"],"offsets":[[34,51]],"normalized":[{"db_name":"MESH","db_id":"D016651"}]},{"id":"5","type":"Disease","text":["toxicity"],"offsets":[[52,60]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"6","type":"Disease","text":["tricuspid regurgitation"],"offsets":[[105,128]],"normalized":[{"db_name":"MESH","db_id":"D014262"}]},{"id":"7","type":"Disease","text":["atrial flutter"],"offsets":[[130,144]],"normalized":[{"db_name":"MESH","db_id":"D001282"}]},{"id":"8","type":"Disease","text":["congestive heart failure"],"offsets":[[146,170]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"9","type":"Chemical","text":["lithium"],"offsets":[[189,196]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"10","type":"Disease","text":["tricuspid regurgitation"],"offsets":[[265,288]],"normalized":[{"db_name":"MESH","db_id":"D014262"}]},{"id":"11","type":"Disease","text":["atrial flutter"],"offsets":[[293,307]],"normalized":[{"db_name":"MESH","db_id":"D001282"}]},{"id":"12","type":"Disease","text":["cardiac disease"],"offsets":[[345,360]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"13","type":"Chemical","text":["lithium"],"offsets":[[386,393]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"14","type":"Chemical","text":["Lithium carbonate"],"offsets":[[511,528]],"normalized":[{"db_name":"MESH","db_id":"D016651"}]},{"id":"15","type":"Disease","text":["congenital heart disease"],"offsets":[[576,600]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"16","type":"Disease","text":["neurologic depression"],"offsets":[[651,672]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"17","type":"Disease","text":["cyanosis"],"offsets":[[674,682]],"normalized":[{"db_name":"MESH","db_id":"D003490"}]},{"id":"18","type":"Disease","text":["cardiac arrhythmia"],"offsets":[[688,706]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]}],"events":[],"coreferences":[],"relations":[{"id":"19","type":"CID","arg1_id":"4","arg2_id":"17","normalized":[]},{"id":"20","type":"CID","arg1_id":"14","arg2_id":"17","normalized":[]},{"id":"21","type":"CID","arg1_id":"4","arg2_id":"18","normalized":[]},{"id":"22","type":"CID","arg1_id":"14","arg2_id":"18","normalized":[]},{"id":"23","type":"CID","arg1_id":"4","arg2_id":"16","normalized":[]},{"id":"24","type":"CID","arg1_id":"14","arg2_id":"16","normalized":[]}]}
{"id":"25","document_id":"6504332","passages":[{"id":"26","type":"title","text":["Phenobarbital-induced dyskinesia in a neurologically-impaired child."],"offsets":[[0,68]]},{"id":"27","type":"abstract","text":["A 2-year-old child with known neurologic impairment developed a dyskinesia soon after starting phenobarbital therapy for seizures. Known causes of movement disorders were eliminated after evaluation. On repeat challenge with phenobarbital, the dyskinesia recurred. Phenobarbital should be added to the list of anticonvulsant drugs that can cause movement disorders."],"offsets":[[69,434]]}],"entities":[{"id":"28","type":"Chemical","text":["Phenobarbital"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"29","type":"Disease","text":["dyskinesia"],"offsets":[[22,32]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"30","type":"Disease","text":["neurologically-impaired"],"offsets":[[38,61]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"31","type":"Disease","text":["neurologic impairment"],"offsets":[[99,120]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"32","type":"Disease","text":["dyskinesia"],"offsets":[[133,143]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"33","type":"Chemical","text":["phenobarbital"],"offsets":[[164,177]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"34","type":"Disease","text":["seizures"],"offsets":[[190,198]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"35","type":"Disease","text":["movement disorders"],"offsets":[[216,234]],"normalized":[{"db_name":"MESH","db_id":"D009069"}]},{"id":"36","type":"Chemical","text":["phenobarbital"],"offsets":[[294,307]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"37","type":"Disease","text":["dyskinesia"],"offsets":[[313,323]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"38","type":"Chemical","text":["Phenobarbital"],"offsets":[[334,347]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"39","type":"Disease","text":["movement disorders"],"offsets":[[415,433]],"normalized":[{"db_name":"MESH","db_id":"D009069"}]}],"events":[],"coreferences":[],"relations":[{"id":"40","type":"CID","arg1_id":"28","arg2_id":"29","normalized":[]},{"id":"41","type":"CID","arg1_id":"28","arg2_id":"32","normalized":[]},{"id":"42","type":"CID","arg1_id":"28","arg2_id":"37","normalized":[]},{"id":"43","type":"CID","arg1_id":"33","arg2_id":"29","normalized":[]},{"id":"44","type":"CID","arg1_id":"33","arg2_id":"32","normalized":[]},{"id":"45","type":"CID","arg1_id":"33","arg2_id":"37","normalized":[]},{"id":"46","type":"CID","arg1_id":"36","arg2_id":"29","normalized":[]},{"id":"47","type":"CID","arg1_id":"36","arg2_id":"32","normalized":[]},{"id":"48","type":"CID","arg1_id":"36","arg2_id":"37","normalized":[]},{"id":"49","type":"CID","arg1_id":"38","arg2_id":"29","normalized":[]},{"id":"50","type":"CID","arg1_id":"38","arg2_id":"32","normalized":[]},{"id":"51","type":"CID","arg1_id":"38","arg2_id":"37","normalized":[]}]}
{"id":"52","document_id":"6436733","passages":[{"id":"53","type":"title","text":["Acute changes of blood ammonia may predict short-term adverse effects of valproic acid."],"offsets":[[0,87]]},{"id":"54","type":"abstract","text":["Valproic acid (VPA) was given to 24 epileptic patients who were already being treated with other antiepileptic drugs. A standardized loading dose of VPA was administered, and venous blood was sampled at 0, 1, 2, 3, and 4 hours. Ammonia (NH3) was higher in patients who, during continuous therapy, complained of drowsiness (7 patients) than in those who were symptom-free (17 patients), although VPA plasma levels were similar in both groups. By measuring VPA-induced changes of blood NH3 content, it may be possible to identify patients at higher risk of obtundation when VPA is given chronically."],"offsets":[[88,685]]}],"entities":[{"id":"55","type":"Chemical","text":["ammonia"],"offsets":[[23,30]],"normalized":[{"db_name":"MESH","db_id":"D000641"}]},{"id":"56","type":"Chemical","text":["valproic acid"],"offsets":[[73,86]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"57","type":"Chemical","text":["Valproic acid"],"offsets":[[88,101]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"58","type":"Chemical","text":["VPA"],"offsets":[[103,106]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"59","type":"Disease","text":["epileptic"],"offsets":[[124,133]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"60","type":"Chemical","text":["VPA"],"offsets":[[237,240]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"61","type":"Chemical","text":["Ammonia"],"offsets":[[316,323]],"normalized":[{"db_name":"MESH","db_id":"D000641"}]},{"id":"62","type":"Chemical","text":["NH3"],"offsets":[[325,328]],"normalized":[{"db_name":"MESH","db_id":"D000641"}]},{"id":"63","type":"Disease","text":["drowsiness"],"offsets":[[399,409]],"normalized":[{"db_name":"MESH","db_id":"D006970"}]},{"id":"64","type":"Chemical","text":["VPA"],"offsets":[[483,486]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"65","type":"Chemical","text":["VPA"],"offsets":[[543,546]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"66","type":"Chemical","text":["NH3"],"offsets":[[572,575]],"normalized":[{"db_name":"MESH","db_id":"D000641"}]},{"id":"67","type":"Chemical","text":["VPA"],"offsets":[[660,663]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]}],"events":[],"coreferences":[],"relations":[{"id":"68","type":"CID","arg1_id":"56","arg2_id":"63","normalized":[]},{"id":"69","type":"CID","arg1_id":"57","arg2_id":"63","normalized":[]},{"id":"70","type":"CID","arg1_id":"58","arg2_id":"63","normalized":[]},{"id":"71","type":"CID","arg1_id":"60","arg2_id":"63","normalized":[]},{"id":"72","type":"CID","arg1_id":"64","arg2_id":"63","normalized":[]},{"id":"73","type":"CID","arg1_id":"65","arg2_id":"63","normalized":[]},{"id":"74","type":"CID","arg1_id":"67","arg2_id":"63","normalized":[]},{"id":"75","type":"CID","arg1_id":"55","arg2_id":"63","normalized":[]},{"id":"76","type":"CID","arg1_id":"61","arg2_id":"63","normalized":[]},{"id":"77","type":"CID","arg1_id":"62","arg2_id":"63","normalized":[]},{"id":"78","type":"CID","arg1_id":"66","arg2_id":"63","normalized":[]}]}
{"id":"79","document_id":"6293644","passages":[{"id":"80","type":"title","text":["Effects of calcitonin on rat extrapyramidal motor system: behavioral and biochemical data."],"offsets":[[0,90]]},{"id":"81","type":"abstract","text":["The effects of i.v.c. injection of human and salmon calcitonin on biochemical and behavioral parameters related to the extrapyramidal motor system, were investigated in male rats. Calcitonin injection resulted in a potentiation of haloperidol-induced catalepsy and a partial prevention of apomorphine-induced hyperactivity. Moreover calcitonin induced a significant decrease in nigral GAD activity but no change in striatal DA and DOPAC concentration or GAD activity. The results are discussed in view of a primary action of calcitonin on the striatonigral GABAergic pathway mediating the DA-related behavioral messages of striatal origin."],"offsets":[[91,730]]}],"entities":[{"id":"82","type":"Chemical","text":["haloperidol"],"offsets":[[322,333]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"83","type":"Disease","text":["catalepsy"],"offsets":[[342,351]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"84","type":"Chemical","text":["apomorphine"],"offsets":[[380,391]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"85","type":"Disease","text":["hyperactivity"],"offsets":[[400,413]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"86","type":"Chemical","text":["DA"],"offsets":[[515,517]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"87","type":"Chemical","text":["DOPAC"],"offsets":[[522,527]],"normalized":[{"db_name":"MESH","db_id":"D015102"}]},{"id":"88","type":"Chemical","text":["DA"],"offsets":[[680,682]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]}],"events":[],"coreferences":[],"relations":[{"id":"89","type":"CID","arg1_id":"82","arg2_id":"83","normalized":[]},{"id":"90","type":"CID","arg1_id":"84","arg2_id":"85","normalized":[]}]}
{"id":"91","document_id":"6203632","passages":[{"id":"92","type":"title","text":["Development of isoproterenol-induced cardiac hypertrophy."],"offsets":[[0,57]]},{"id":"93","type":"abstract","text":["The development of cardiac hypertrophy was studied in adult female Wistar rats following daily subcutaneous injections of isoproterenol (ISO) (0.3 mg\/kg body weight). A time course was established for the change in tissue mass, RNA and DNA content, as well as hydroxyproline content. Heart weight increased 44% after 8 days of treatment with a half time of 3.4 days. Ventricular RNA content was elevated 26% after 24 h of a single injection and reached a maximal level following 8 days of therapy. The half time for RNA accumulation was 2.0 days. The total content of hydroxyproline remained stable during the first 2 days of treatment but increased 46% after 4 days of therapy. Ventricular DNA content was unchanged during the early stage (1-4 days) of hypertrophic growth but increased to a new steady-state level 19% above the controls after 8 days of treatment. Intraventricular pressures and coronary flow measures were similar for control and experimental animals following 4 days of developed hypertrophy. However, dP\/dt in the ISO-treated hearts was slightly but significantly (P less than 0.05) elevated. These data indicate that the adaptive response to ISO shows an early hypertrophic phase (1-4 days) characterized by a substantial increase in RNA content and cardiac mass in the absence of changes in DNA. However, prolonged stimulation (8-12 days) appears to represent a complex integration of both cellular hypertrophy and hyperplasia within the heart."],"offsets":[[58,1525]]}],"entities":[{"id":"94","type":"Chemical","text":["isoproterenol"],"offsets":[[15,28]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"95","type":"Disease","text":["cardiac hypertrophy"],"offsets":[[37,56]],"normalized":[{"db_name":"MESH","db_id":"D006332"}]},{"id":"96","type":"Disease","text":["cardiac hypertrophy"],"offsets":[[77,96]],"normalized":[{"db_name":"MESH","db_id":"D006332"}]},{"id":"97","type":"Chemical","text":["isoproterenol"],"offsets":[[180,193]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"98","type":"Chemical","text":["ISO"],"offsets":[[195,198]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"99","type":"Chemical","text":["hydroxyproline"],"offsets":[[318,332]],"normalized":[{"db_name":"MESH","db_id":"D006909"}]},{"id":"100","type":"Chemical","text":["hydroxyproline"],"offsets":[[626,640]],"normalized":[{"db_name":"MESH","db_id":"D006909"}]},{"id":"101","type":"Disease","text":["hypertrophic"],"offsets":[[812,824]],"normalized":[{"db_name":"MESH","db_id":"D006984"}]},{"id":"102","type":"Disease","text":["hypertrophy"],"offsets":[[1058,1069]],"normalized":[{"db_name":"MESH","db_id":"D006984"}]},{"id":"103","type":"Chemical","text":["ISO"],"offsets":[[1093,1096]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"104","type":"Chemical","text":["ISO"],"offsets":[[1222,1225]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"105","type":"Disease","text":["hypertrophic"],"offsets":[[1241,1253]],"normalized":[{"db_name":"MESH","db_id":"D006984"}]},{"id":"106","type":"Disease","text":["hypertrophy"],"offsets":[[1480,1491]],"normalized":[{"db_name":"MESH","db_id":"D006984"}]},{"id":"107","type":"Disease","text":["hyperplasia"],"offsets":[[1496,1507]],"normalized":[{"db_name":"MESH","db_id":"D006965"}]}],"events":[],"coreferences":[],"relations":[{"id":"108","type":"CID","arg1_id":"94","arg2_id":"95","normalized":[]},{"id":"109","type":"CID","arg1_id":"94","arg2_id":"96","normalized":[]},{"id":"110","type":"CID","arg1_id":"97","arg2_id":"95","normalized":[]},{"id":"111","type":"CID","arg1_id":"97","arg2_id":"96","normalized":[]},{"id":"112","type":"CID","arg1_id":"98","arg2_id":"95","normalized":[]},{"id":"113","type":"CID","arg1_id":"98","arg2_id":"96","normalized":[]},{"id":"114","type":"CID","arg1_id":"103","arg2_id":"95","normalized":[]},{"id":"115","type":"CID","arg1_id":"103","arg2_id":"96","normalized":[]},{"id":"116","type":"CID","arg1_id":"104","arg2_id":"95","normalized":[]},{"id":"117","type":"CID","arg1_id":"104","arg2_id":"96","normalized":[]},{"id":"118","type":"CID","arg1_id":"94","arg2_id":"107","normalized":[]},{"id":"119","type":"CID","arg1_id":"97","arg2_id":"107","normalized":[]},{"id":"120","type":"CID","arg1_id":"98","arg2_id":"107","normalized":[]},{"id":"121","type":"CID","arg1_id":"103","arg2_id":"107","normalized":[]},{"id":"122","type":"CID","arg1_id":"104","arg2_id":"107","normalized":[]}]}
{"id":"123","document_id":"3131282","passages":[{"id":"124","type":"title","text":["Co-carcinogenic effect of retinyl acetate on forestomach carcinogenesis of male F344 rats induced with butylated hydroxyanisole."],"offsets":[[0,128]]},{"id":"125","type":"abstract","text":["The potential modifying effect of retinyl acetate (RA) on butylated hydroxyanisole (BHA)-induced rat forestomach tumorigenesis was examined. Male F344 rats, 5 weeks of age, were maintained on diet containing 1% or 2% BHA by weight and simultaneously on drinking water supplemented with RA at various concentrations (w\/v) for 52 weeks. In groups given 2% BHA, although marked hyperplastic changes of the forestomach epithelium were observed in all animals, co-administration of 0.25% RA significantly (P less than 0.05) increased the incidence of forestomach tumors (squamous cell papilloma and carcinoma) to 60% (9\/15, 2 rats with carcinoma) from 15% (3\/20, one rat with carcinoma) in the group given RA-free water. In rats given 1% BHA, RA co-administered at a dose of 0.05, 0.1, 0.2 or 0.25% showed a dose-dependent enhancing effect on the development of the BHA-induced epithelial hyperplasia. Tumors, all papillomas, were induced in 3 rats (17%) with 0.25% RA and in one rat (10%) with 0.05% RA co-administration. RA alone did not induce hyperplastic changes in the forestomach. These findings indicate that RA acted as a co-carcinogen in the BHA forestomach carcinogenesis of the rat."],"offsets":[[129,1318]]}],"entities":[{"id":"126","type":"Disease","text":["carcinogenic"],"offsets":[[3,15]],"normalized":[{"db_name":"MESH","db_id":"D063646"}]},{"id":"127","type":"Chemical","text":["retinyl acetate"],"offsets":[[26,41]],"normalized":[{"db_name":"MESH","db_id":"C009166"}]},{"id":"128","type":"Disease","text":["forestomach carcinogenesis"],"offsets":[[45,71]],"normalized":[{"db_name":"MESH","db_id":"D013274"}]},{"id":"129","type":"Chemical","text":["butylated hydroxyanisole"],"offsets":[[103,127]],"normalized":[{"db_name":"MESH","db_id":"D002083"}]},{"id":"130","type":"Chemical","text":["retinyl acetate"],"offsets":[[163,178]],"normalized":[{"db_name":"MESH","db_id":"C009166"}]},{"id":"131","type":"Chemical","text":["RA"],"offsets":[[180,182]],"normalized":[{"db_name":"MESH","db_id":"C009166"}]},{"id":"132","type":"Chemical","text":["butylated hydroxyanisole"],"offsets":[[187,211]],"normalized":[{"db_name":"MESH","db_id":"D002083"}]},{"id":"133","type":"Chemical","text":["BHA"],"offsets":[[213,216]],"normalized":[{"db_name":"MESH","db_id":"D002083"}]},{"id":"134","type":"Disease","text":["forestomach tumorigenesis"],"offsets":[[230,255]],"normalized":[{"db_name":"MESH","db_id":"D013274"}]},{"id":"135","type":"Chemical","text":["BHA"],"offsets":[[346,349]],"normalized":[{"db_name":"MESH","db_id":"D002083"}]},{"id":"136","type":"Chemical","text":["RA"],"offsets":[[415,417]],"normalized":[{"db_name":"MESH","db_id":"C009166"}]},{"id":"137","type":"Chemical","text":["BHA"],"offsets":[[483,486]],"normalized":[{"db_name":"MESH","db_id":"D002083"}]},{"id":"138","type":"Chemical","text":["RA"],"offsets":[[612,614]],"normalized":[{"db_name":"MESH","db_id":"C009166"}]},{"id":"139","type":"Disease","text":["forestomach tumors"],"offsets":[[675,693]],"normalized":[{"db_name":"MESH","db_id":"D013274"}]},{"id":"140","type":"Disease","text":["squamous cell 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{"id":"189","document_id":"3115150","passages":[{"id":"190","type":"title","text":["Ketanserin pretreatment reverses alfentanil-induced muscle rigidity."],"offsets":[[0,68]]},{"id":"191","type":"abstract","text":["Systemic pretreatment with ketanserin, a relatively specific type-2 serotonin receptor antagonist, significantly attenuated the muscle rigidity produced in rats by the potent short-acting opiate agonist alfentanil. Following placement of subcutaneous electrodes in each animal's left gastrocnemius muscle, rigidity was assessed by analyzing root-mean-square electromyographic activity. Intraperitoneal ketanserin administration at doses of 0.63 and 2.5 mg\/kg prevented the alfentanil-induced increase in electromyographic activity compared with animals pretreated with saline. Chlordiazepoxide at doses up to 10 mg\/kg failed to significantly influence the rigidity produced by alfentanil. Despite the absence of rigidity, animals that received ketanserin (greater than 0.31 mg\/kg i.p.) followed by alfentanil were motionless, flaccid, and less responsive to external stimuli than were animals receiving alfentanil alone. Rats that received ketanserin and alfentanil exhibited less rearing and exploratory behavior at the end of the 60-min recording period than did animals that received ketanserin alone. These results, in combination with previous work, suggest that muscle rigidity, a clinically relevant side-effect of parenteral narcotic administration, may be partly mediated via serotonergic pathways. Pretreatment with type-2 serotonin antagonists may be clinically useful in attenuating opiate-induced rigidity, although further studies will be necessary to assess the interaction of possibly enhanced CNS, cardiovascular, and respiratory depression."],"offsets":[[69,1627]]}],"entities":[{"id":"192","type":"Chemical","text":["Ketanserin"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D007650"}]},{"id":"193","type":"Chemical","text":["alfentanil"],"offsets":[[33,43]],"normalized":[{"db_name":"MESH","db_id":"D015760"}]},{"id":"194","type":"Disease","text":["muscle rigidity"],"offsets":[[52,67]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"195","type":"Chemical","text":["ketanserin"],"offsets":[[96,106]],"normalized":[{"db_name":"MESH","db_id":"D007650"}]},{"id":"196","type":"Chemical","text":["serotonin"],"offsets":[[137,146]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"197","type":"Disease","text":["muscle 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{"id":"267","document_id":"2917114","passages":[{"id":"268","type":"title","text":["Glycopyrronium requirements for antagonism of the muscarinic side effects of edrophonium."],"offsets":[[0,89]]},{"id":"269","type":"abstract","text":["We have compared, in 60 adult patients, the cardiovascular effects of glycopyrronium 5 micrograms kg-1 and 10 micrograms kg-1 given either simultaneously or 1 min before edrophonium 1 mg kg-1. Significant differences between the four groups were detected (P less than 0.001). Both groups receiving 10 micrograms kg-1 showed increases in heart rate of up to 30 beat min-1 (95% confidence limits 28-32 beat min-1). Use of glycopyrronium 5 micrograms kg-1 provided greater cardiovascular stability and, given 1 min before the edrophonium, was sufficient to minimize early, edrophonium-induced bradycardias. This low dose of glycopyrronium provided good control of oropharyngeal secretions."],"offsets":[[90,776]]}],"entities":[{"id":"270","type":"Chemical","text":["Glycopyrronium"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D006024"}]},{"id":"271","type":"Chemical","text":["edrophonium"],"offsets":[[77,88]],"normalized":[{"db_name":"MESH","db_id":"D004491"}]},{"id":"272","type":"Chemical","text":["glycopyrronium"],"offsets":[[160,174]],"normalized":[{"db_name":"MESH","db_id":"D006024"}]},{"id":"273","type":"Chemical","text":["edrophonium"],"offsets":[[260,271]],"normalized":[{"db_name":"MESH","db_id":"D004491"}]},{"id":"274","type":"Chemical","text":["glycopyrronium"],"offsets":[[510,524]],"normalized":[{"db_name":"MESH","db_id":"D006024"}]},{"id":"275","type":"Chemical","text":["edrophonium"],"offsets":[[613,624]],"normalized":[{"db_name":"MESH","db_id":"D004491"}]},{"id":"276","type":"Chemical","text":["edrophonium"],"offsets":[[660,671]],"normalized":[{"db_name":"MESH","db_id":"D004491"}]},{"id":"277","type":"Disease","text":["bradycardias"],"offsets":[[680,692]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"278","type":"Chemical","text":["glycopyrronium"],"offsets":[[711,725]],"normalized":[{"db_name":"MESH","db_id":"D006024"}]}],"events":[],"coreferences":[],"relations":[{"id":"279","type":"CID","arg1_id":"271","arg2_id":"277","normalized":[]},{"id":"280","type":"CID","arg1_id":"273","arg2_id":"277","normalized":[]},{"id":"281","type":"CID","arg1_id":"275","arg2_id":"277","normalized":[]},{"id":"282","type":"CID","arg1_id":"276","arg2_id":"277","normalized":[]}]}
{"id":"283","document_id":"2564649","passages":[{"id":"284","type":"title","text":["Involvement of locus coeruleus and noradrenergic neurotransmission in fentanyl-induced muscular rigidity in the rat."],"offsets":[[0,116]]},{"id":"285","type":"abstract","text":["Whereas muscular rigidity is a well-known side effect that is associated with high-dose fentanyl anesthesia, a paucity of information exists with regard to its underlying mechanism(s). We investigated in this study the possible engagement of locus coeruleus of the pons in this phenomenon, using male Sprague-Dawley rats anesthetized with ketamine. Under proper control of respiration, body temperature and end-tidal CO2, intravenous administration of fentanyl (50 or 100 micrograms\/kg) consistently promoted an increase in electromyographic activity recorded from the gastrocnemius and abdominal rectus muscles. Such an induced muscular rigidity by the narcotic agent was significantly antagonized or even reduced by prior electrolytic lesions of the locus coeruleus or pretreatment with the alpha-adrenoceptor blocker, prazosin. Microinjection of fentanyl (2.5 micrograms\/50 nl) directly into this pontine nucleus, on the other hand, elicited discernible electromyographic excitation. It is speculated that the induction of muscular rigidity by fentanyl may involve the coerulospinal noradrenergic fibers to the spinal motoneurons."],"offsets":[[117,1250]]}],"entities":[{"id":"286","type":"Chemical","text":["fentanyl"],"offsets":[[70,78]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"287","type":"Disease","text":["muscular rigidity"],"offsets":[[87,104]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"288","type":"Disease","text":["muscular rigidity"],"offsets":[[125,142]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"289","type":"Chemical","text":["fentanyl"],"offsets":[[205,213]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"290","type":"Chemical","text":["ketamine"],"offsets":[[456,464]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"291","type":"Chemical","text":["CO2"],"offsets":[[534,537]],"normalized":[{"db_name":"MESH","db_id":"D002245"}]},{"id":"292","type":"Chemical","text":["fentanyl"],"offsets":[[569,577]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"293","type":"Disease","text":["muscular rigidity"],"offsets":[[746,763]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"294","type":"Chemical","text":["prazosin"],"offsets":[[938,946]],"normalized":[{"db_name":"MESH","db_id":"D011224"}]},{"id":"295","type":"Chemical","text":["fentanyl"],"offsets":[[966,974]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"296","type":"Disease","text":["muscular rigidity"],"offsets":[[1143,1160]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"297","type":"Chemical","text":["fentanyl"],"offsets":[[1164,1172]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]}],"events":[],"coreferences":[],"relations":[{"id":"298","type":"CID","arg1_id":"286","arg2_id":"287","normalized":[]},{"id":"299","type":"CID","arg1_id":"286","arg2_id":"288","normalized":[]},{"id":"300","type":"CID","arg1_id":"286","arg2_id":"293","normalized":[]},{"id":"301","type":"CID","arg1_id":"286","arg2_id":"296","normalized":[]},{"id":"302","type":"CID","arg1_id":"289","arg2_id":"287","normalized":[]},{"id":"303","type":"CID","arg1_id":"289","arg2_id":"288","normalized":[]},{"id":"304","type":"CID","arg1_id":"289","arg2_id":"293","normalized":[]},{"id":"305","type":"CID","arg1_id":"289","arg2_id":"296","normalized":[]},{"id":"306","type":"CID","arg1_id":"292","arg2_id":"287","normalized":[]},{"id":"307","type":"CID","arg1_id":"292","arg2_id":"288","normalized":[]},{"id":"308","type":"CID","arg1_id":"292","arg2_id":"293","normalized":[]},{"id":"309","type":"CID","arg1_id":"292","arg2_id":"296","normalized":[]},{"id":"310","type":"CID","arg1_id":"295","arg2_id":"287","normalized":[]},{"id":"311","type":"CID","arg1_id":"295","arg2_id":"288","normalized":[]},{"id":"312","type":"CID","arg1_id":"295","arg2_id":"293","normalized":[]},{"id":"313","type":"CID","arg1_id":"295","arg2_id":"296","normalized":[]},{"id":"314","type":"CID","arg1_id":"297","arg2_id":"287","normalized":[]},{"id":"315","type":"CID","arg1_id":"297","arg2_id":"288","normalized":[]},{"id":"316","type":"CID","arg1_id":"297","arg2_id":"293","normalized":[]},{"id":"317","type":"CID","arg1_id":"297","arg2_id":"296","normalized":[]}]}
{"id":"318","document_id":"2339463","passages":[{"id":"319","type":"title","text":["Cerebral sinus thrombosis as a potential hazard of antifibrinolytic treatment in menorrhagia."],"offsets":[[0,93]]},{"id":"320","type":"abstract","text":["We describe a 42-year-old woman who developed superior sagittal and left transverse sinus thrombosis associated with prolonged epsilon-aminocaproic acid therapy for menorrhagia. This antifibrinolytic agent has been used in women with menorrhagia to promote clotting and reduce blood loss. Although increased risk of thromboembolic disease has been reported during treatment with epsilon-aminocaproic acid, cerebral sinus thrombosis has not been previously described. Careful use of epsilon-aminocaproic acid therapy is recommended."],"offsets":[[94,625]]}],"entities":[{"id":"321","type":"Disease","text":["Cerebral sinus thrombosis"],"offsets":[[0,25]],"normalized":[{"db_name":"MESH","db_id":"D012851"}]},{"id":"322","type":"Disease","text":["menorrhagia"],"offsets":[[81,92]],"normalized":[{"db_name":"MESH","db_id":"D008595"}]},{"id":"323","type":"Disease","text":["sagittal and left transverse sinus thrombosis"],"offsets":[[149,194]],"normalized":[{"db_name":"MESH","db_id":"D020225"},{"db_name":"MESH","db_id":"D020227"}]},{"id":"324","type":"Disease","text":["sagittal","sinus thrombosis"],"offsets":[[149,157],[178,194]],"normalized":[{"db_name":"MESH","db_id":"D020225"}]},{"id":"325","type":"Disease","text":["left transverse sinus thrombosis"],"offsets":[[162,194]],"normalized":[{"db_name":"MESH","db_id":"D020227"}]},{"id":"326","type":"Chemical","text":["epsilon-aminocaproic acid"],"offsets":[[221,246]],"normalized":[{"db_name":"MESH","db_id":"D015119"}]},{"id":"327","type":"Disease","text":["menorrhagia"],"offsets":[[259,270]],"normalized":[{"db_name":"MESH","db_id":"D008595"}]},{"id":"328","type":"Disease","text":["menorrhagia"],"offsets":[[328,339]],"normalized":[{"db_name":"MESH","db_id":"D008595"}]},{"id":"329","type":"Disease","text":["blood loss"],"offsets":[[371,381]],"normalized":[{"db_name":"MESH","db_id":"D006473"}]},{"id":"330","type":"Disease","text":["thromboembolic disease"],"offsets":[[410,432]],"normalized":[{"db_name":"MESH","db_id":"D013923"}]},{"id":"331","type":"Chemical","text":["epsilon-aminocaproic acid"],"offsets":[[473,498]],"normalized":[{"db_name":"MESH","db_id":"D015119"}]},{"id":"332","type":"Disease","text":["cerebral sinus thrombosis"],"offsets":[[500,525]],"normalized":[{"db_name":"MESH","db_id":"D012851"}]},{"id":"333","type":"Chemical","text":["epsilon-aminocaproic acid"],"offsets":[[576,601]],"normalized":[{"db_name":"MESH","db_id":"D015119"}]}],"events":[],"coreferences":[],"relations":[{"id":"334","type":"CID","arg1_id":"326","arg2_id":"323","normalized":[]},{"id":"335","type":"CID","arg1_id":"326","arg2_id":"324","normalized":[]},{"id":"336","type":"CID","arg1_id":"331","arg2_id":"323","normalized":[]},{"id":"337","type":"CID","arg1_id":"331","arg2_id":"324","normalized":[]},{"id":"338","type":"CID","arg1_id":"333","arg2_id":"323","normalized":[]},{"id":"339","type":"CID","arg1_id":"333","arg2_id":"324","normalized":[]}]}
{"id":"340","document_id":"1545575","passages":[{"id":"341","type":"title","text":["Hemorrhagic cystitis complicating bone marrow transplantation."],"offsets":[[0,62]]},{"id":"342","type":"abstract","text":["Hemorrhagic cystitis is a potentially serious complication of high-dose cyclophosphamide therapy administered before bone marrow transplantation. As standard practice at our institution, patients who are scheduled to receive a bone marrow transplant are treated prophylactically with forced hydration and bladder irrigation. In an attempt to obviate the inconvenience of bladder irrigation, we conducted a feasibility trial of uroprophylaxis with mesna, which neutralizes the hepatic metabolite of cyclophosphamide that causes hemorrhagic cystitis. Of 97 patients who received standard prophylaxis, 4 had symptomatic hemorrhagic cystitis. In contrast, two of four consecutive patients who received mesna uroprophylaxis before allogeneic bone marrow transplantation had severe hemorrhagic cystitis for at least 2 weeks. Because of this suboptimal result, we resumed the use of bladder irrigation and forced hydration to minimize the risk of hemorrhagic cystitis."],"offsets":[[63,1024]]}],"entities":[{"id":"343","type":"Disease","text":["Hemorrhagic cystitis"],"offsets":[[0,20]],"normalized":[{"db_name":"MESH","db_id":"D006470"},{"db_name":"MESH","db_id":"D003556"}]},{"id":"344","type":"Disease","text":["Hemorrhagic"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"345","type":"Disease","text":["cystitis"],"offsets":[[12,20]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"346","type":"Disease","text":["Hemorrhagic cystitis"],"offsets":[[63,83]],"normalized":[{"db_name":"MESH","db_id":"D006470"},{"db_name":"MESH","db_id":"D003556"}]},{"id":"347","type":"Disease","text":["Hemorrhagic"],"offsets":[[63,74]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"348","type":"Disease","text":["cystitis"],"offsets":[[75,83]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"349","type":"Chemical","text":["cyclophosphamide"],"offsets":[[135,151]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"350","type":"Chemical","text":["mesna"],"offsets":[[510,515]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"351","type":"Chemical","text":["cyclophosphamide"],"offsets":[[561,577]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"352","type":"Disease","text":["hemorrhagic cystitis"],"offsets":[[590,610]],"normalized":[{"db_name":"MESH","db_id":"D006470"},{"db_name":"MESH","db_id":"D003556"}]},{"id":"353","type":"Disease","text":["hemorrhagic"],"offsets":[[590,601]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"354","type":"Disease","text":["cystitis"],"offsets":[[602,610]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"355","type":"Disease","text":["hemorrhagic cystitis"],"offsets":[[680,700]],"normalized":[{"db_name":"MESH","db_id":"D006470"},{"db_name":"MESH","db_id":"D003556"}]},{"id":"356","type":"Disease","text":["hemorrhagic"],"offsets":[[680,691]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"357","type":"Disease","text":["cystitis"],"offsets":[[692,700]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"358","type":"Chemical","text":["mesna"],"offsets":[[761,766]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"359","type":"Disease","text":["hemorrhagic cystitis"],"offsets":[[839,859]],"normalized":[{"db_name":"MESH","db_id":"D006470"},{"db_name":"MESH","db_id":"D003556"}]},{"id":"360","type":"Disease","text":["hemorrhagic"],"offsets":[[839,850]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"361","type":"Disease","text":["cystitis"],"offsets":[[851,859]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"362","type":"Disease","text":["hemorrhagic 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{"id":"413","document_id":"1286498","passages":[{"id":"414","type":"title","text":["Reversal of central benzodiazepine effects by flumazenil after intravenous conscious sedation with diazepam and opioids: report of a double-blind multicenter study. The Flumazenil in Intravenous Conscious Sedation with Diazepam Multicenter Study Group II."],"offsets":[[0,255]]},{"id":"415","type":"abstract","text":["The efficacy and safety of a new benzodiazepine antagonist, flumazenil, were assessed in a double-blind multicenter study. Flumazenil (mean dose, 0.76 mg) or placebo (mean dose, 8.9 ml) was administered intravenously to 130 and 67 patients, respectively, who had been given diazepam in conjunction with an opioid (fentanyl, meperidine, or morphine) for the induction and maintenance of intravenous conscious sedation for diagnostic or therapeutic surgical procedures. The group assessable for efficacy comprised 122 patients treated with flumazenil and 64 patients given placebo. After 5 minutes, 80\/115 (70%) flumazenil-treated patients, compared with 21\/63 (33%) placebo-treated patients, were completely awake and alert, as indicated by a score of 5 on the Observer's Assessment of Alertness\/Sedation Scale. Ninety-five percent of patients in each group who attained a score of 5 at the 5-minute assessment showed no loss of alertness throughout the 180-minute assessment period. Flumazenil-treated patients also performed significantly better on the Finger-to-Nose Test and the recall of pictures shown at the 5-minute assessment. Flumazenil was well tolerated, with no serious adverse effects reported. Thirty-nine (30%) of flumazenil-treated patients, compared with 17 (25%) of placebo-treated patients had one or more drug-related adverse experiences. The most common adverse effects were nausea and vomiting in the flumazenil group and nausea and injection-site pain in the placebo group. Flumazenil was found to promptly reverse sedation induced by diazepam in the presence of opioids."],"offsets":[[256,1850]]}],"entities":[{"id":"416","type":"Chemical","text":["benzodiazepine"],"offsets":[[20,34]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]},{"id":"417","type":"Chemical","text":["flumazenil"],"offsets":[[46,56]],"normalized":[{"db_name":"MESH","db_id":"D005442"}]},{"id":"418","type":"Chemical","text":["diazepam"],"offsets":[[99,107]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"419","type":"Chemical","text":["Flumazenil"],"offsets":[[169,179]],"normalized":[{"db_name":"MESH","db_id":"D005442"}]},{"id":"420","type":"Chemical","text":["Diazepam"],"offsets":[[219,227]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"421","type":"Chemical","text":["benzodiazepine"],"offsets":[[289,303]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]},{"id":"422","type":"Chemical","text":["flumazenil"],"offsets":[[316,326]],"normalized":[{"db_name":"MESH","db_id":"D005442"}]},{"id":"423","type":"Chemical","text":["Flumazenil"],"offsets":[[379,389]],"normalized":[{"db_name":"MESH","db_id":"D005442"}]},{"id":"424","type":"Chemical","text":["diazepam"],"offsets":[[530,538]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"425","type":"Chemical","text":["fentanyl"],"offsets":[[570,578]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"426","type":"Chemical","text":["meperidine"],"offsets":[[580,590]],"normalized":[{"db_name":"MESH","db_id":"D008614"}]},{"id":"427","type":"Chemical","text":["morphine"],"offsets":[[595,603]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"428","type":"Chemical","text":["flumazenil"],"offsets":[[794,804]],"normalized":[{"db_name":"MESH","db_id":"D005442"}]},{"id":"429","type":"Chemical","text":["flumazenil"],"offsets":[[866,876]],"normalized":[{"db_name":"MESH","db_id":"D005442"}]},{"id":"430","type":"Chemical","text":["Flumazenil"],"offsets":[[1239,1249]],"normalized":[{"db_name":"MESH","db_id":"D005442"}]},{"id":"431","type":"Chemical","text":["Flumazenil"],"offsets":[[1391,1401]],"normalized":[{"db_name":"MESH","db_id":"D005442"}]},{"id":"432","type":"Chemical","text":["flumazenil"],"offsets":[[1485,1495]],"normalized":[{"db_name":"MESH","db_id":"D005442"}]},{"id":"433","type":"Disease","text":["nausea"],"offsets":[[1652,1658]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"434","type":"Disease","text":["vomiting"],"offsets":[[1663,1671]],"normalized":[{"db_name":"MESH","db_id":"D014839"}]},{"id":"435","type":"Chemical","text":["flumazenil"],"offsets":[[1679,1689]],"normalized":[{"db_name":"MESH","db_id":"D005442"}]},{"id":"436","type":"Disease","text":["nausea"],"offsets":[[1700,1706]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"437","type":"Disease","text":["pain"],"offsets":[[1726,1730]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"438","type":"Chemical","text":["Flumazenil"],"offsets":[[1753,1763]],"normalized":[{"db_name":"MESH","db_id":"D005442"}]},{"id":"439","type":"Chemical","text":["diazepam"],"offsets":[[1814,1822]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]}],"events":[],"coreferences":[],"relations":[{"id":"440","type":"CID","arg1_id":"417","arg2_id":"433","normalized":[]},{"id":"441","type":"CID","arg1_id":"417","arg2_id":"436","normalized":[]},{"id":"442","type":"CID","arg1_id":"419","arg2_id":"433","normalized":[]},{"id":"443","type":"CID","arg1_id":"419","arg2_id":"436","normalized":[]},{"id":"444","type":"CID","arg1_id":"422","arg2_id":"433","normalized":[]},{"id":"445","type":"CID","arg1_id":"422","arg2_id":"436","normalized":[]},{"id":"446","type":"CID","arg1_id":"423","arg2_id":"433","normalized":[]},{"id":"447","type":"CID","arg1_id":"423","arg2_id":"436","normalized":[]},{"id":"448","type":"CID","arg1_id":"428","arg2_id":"433","normalized":[]},{"id":"449","type":"CID","arg1_id":"428","arg2_id":"436","normalized":[]},{"id":"450","type":"CID","arg1_id":"429","arg2_id":"433","normalized":[]},{"id":"451","type":"CID","arg1_id":"429","arg2_id":"436","normalized":[]},{"id":"452","type":"CID","arg1_id":"430","arg2_id":"433","normalized":[]},{"id":"453","type":"CID","arg1_id":"430","arg2_id":"436","normalized":[]},{"id":"454","type":"CID","arg1_id":"431","arg2_id":"433","normalized":[]},{"id":"455","type":"CID","arg1_id":"431","arg2_id":"436","normalized":[]},{"id":"456","type":"CID","arg1_id":"432","arg2_id":"433","normalized":[]},{"id":"457","type":"CID","arg1_id":"432","arg2_id":"436","normalized":[]},{"id":"458","type":"CID","arg1_id":"435","arg2_id":"433","normalized":[]},{"id":"459","type":"CID","arg1_id":"435","arg2_id":"436","normalized":[]},{"id":"460","type":"CID","arg1_id":"438","arg2_id":"433","normalized":[]},{"id":"461","type":"CID","arg1_id":"438","arg2_id":"436","normalized":[]},{"id":"462","type":"CID","arg1_id":"417","arg2_id":"434","normalized":[]},{"id":"463","type":"CID","arg1_id":"419","arg2_id":"434","normalized":[]},{"id":"464","type":"CID","arg1_id":"422","arg2_id":"434","normalized":[]},{"id":"465","type":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{"id":"473","document_id":"839274","passages":[{"id":"474","type":"title","text":["Hepatic adenomas and focal nodular hyperplasia of the liver in young women on oral contraceptives: case reports."],"offsets":[[0,112]]},{"id":"475","type":"abstract","text":["Two cases of hepatic adenoma and one of focal nodular hyperplasia presumably associated with the use of oral contraceptives, are reported. Special reference is made to their clinical presentation, which may be totally asymptomatic. Liver-function tests are of little diagnostic value, but valuable information may be obtained from both liver scanning and hepatic angiography. Histologic differences and clinical similarities between hepatic adenoma and focal nodular hyperplasia of the liver are discussed."],"offsets":[[113,619]]}],"entities":[{"id":"476","type":"Disease","text":["adenomas"],"offsets":[[8,16]],"normalized":[{"db_name":"MESH","db_id":"D000236"}]},{"id":"477","type":"Disease","text":["focal nodular hyperplasia"],"offsets":[[21,46]],"normalized":[{"db_name":"MESH","db_id":"D020518"}]},{"id":"478","type":"Chemical","text":["oral contraceptives"],"offsets":[[78,97]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"479","type":"Disease","text":["adenoma"],"offsets":[[134,141]],"normalized":[{"db_name":"MESH","db_id":"D000236"}]},{"id":"480","type":"Disease","text":["focal nodular hyperplasia"],"offsets":[[153,178]],"normalized":[{"db_name":"MESH","db_id":"D020518"}]},{"id":"481","type":"Chemical","text":["oral contraceptives"],"offsets":[[217,236]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"482","type":"Disease","text":["adenoma"],"offsets":[[554,561]],"normalized":[{"db_name":"MESH","db_id":"D000236"}]},{"id":"483","type":"Disease","text":["focal nodular hyperplasia"],"offsets":[[566,591]],"normalized":[{"db_name":"MESH","db_id":"D020518"}]}],"events":[],"coreferences":[],"relations":[{"id":"484","type":"CID","arg1_id":"478","arg2_id":"477","normalized":[]},{"id":"485","type":"CID","arg1_id":"478","arg2_id":"480","normalized":[]},{"id":"486","type":"CID","arg1_id":"478","arg2_id":"483","normalized":[]},{"id":"487","type":"CID","arg1_id":"481","arg2_id":"477","normalized":[]},{"id":"488","type":"CID","arg1_id":"481","arg2_id":"480","normalized":[]},{"id":"489","type":"CID","arg1_id":"481","arg2_id":"483","normalized":[]},{"id":"490","type":"CID","arg1_id":"478","arg2_id":"476","normalized":[]},{"id":"491","type":"CID","arg1_id":"478","arg2_id":"479","normalized":[]},{"id":"492","type":"CID","arg1_id":"478","arg2_id":"482","normalized":[]},{"id":"493","type":"CID","arg1_id":"481","arg2_id":"476","normalized":[]},{"id":"494","type":"CID","arg1_id":"481","arg2_id":"479","normalized":[]},{"id":"495","type":"CID","arg1_id":"481","arg2_id":"482","normalized":[]}]}
{"id":"496","document_id":"591536","passages":[{"id":"497","type":"title","text":["Arterial thromboembolism in patients receiving systemic heparin therapy: a complication associated with heparin-induced thrombocytopenia."],"offsets":[[0,137]]},{"id":"498","type":"abstract","text":["Arterial thromboembolism is a recognized complication of systemic heparin therapy. Characteristic of the entity is arterial occlusion by platelet-fibrin thrombi with distal ischemia occurring four to twenty days after the initiation of heparin therapy, preceded by profound thrombocytopenia with platelet counts in the range of 30,000 to 40,000 per cubic millimeter. The clinically apparent occlusion may be preceded by gastrointestinal and musculoskeletal symptoms that appear to be ischemic in origin, and might serve to warn the clinician of these complications. Previous reports of these phenomena as well as recent studies of the effect of heparin are reviewed. The common factor relating thromboembolism and thrombocytopenia is heparin-induced platelet aggregation. Appropriate treatment consists of discontinuation of heparin, and anticoagulation with sodium warfarin if necessary. Vascular procedures are performed as indicated."],"offsets":[[138,1074]]}],"entities":[{"id":"499","type":"Disease","text":["thromboembolism"],"offsets":[[9,24]],"normalized":[{"db_name":"MESH","db_id":"D013923"}]},{"id":"500","type":"Chemical","text":["heparin"],"offsets":[[56,63]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"501","type":"Chemical","text":["heparin"],"offsets":[[104,111]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"502","type":"Disease","text":["thrombocytopenia"],"offsets":[[120,136]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"503","type":"Disease","text":["thromboembolism"],"offsets":[[147,162]],"normalized":[{"db_name":"MESH","db_id":"D013923"}]},{"id":"504","type":"Chemical","text":["heparin"],"offsets":[[204,211]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"505","type":"Disease","text":["arterial 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{"id":"549","document_id":"20735774","passages":[{"id":"550","type":"title","text":["Long-term prognosis for transplant-free survivors of paracetamol-induced acute liver failure."],"offsets":[[0,93]]},{"id":"551","type":"abstract","text":["BACKGROUND: The prognosis for transplant-free survivors of paracetamol-induced acute liver failure remains unknown. AIM: To examine whether paracetamol-induced acute liver failure increases long-term mortality. METHODS: We followed up all transplant-free survivors of paracetamol-induced acute liver injury, hospitalized in a Danish national referral centre during 1984-2004. We compared age-specific mortality rates from 1 year post-discharge through 2008 between those in whom the liver injury led to an acute liver failure and those in whom it did not. RESULTS: We included 641 patients. On average, age-specific mortality rates were slightly higher for the 101 patients whose paracetamol-induced liver injury had caused an acute liver failure (adjusted mortality rate ratio = 1.70, 95% CI 1.02-2.85), but the association was age-dependent, and no survivors of acute liver failure died of liver disease, whereas suicides were frequent in both groups. These observations speak against long-term effects of acute liver failure. More likely, the elevated mortality rate ratio resulted from incomplete adjustment for the greater prevalence of substance abuse among survivors of acute liver failure. CONCLUSIONS: Paracetamol-induced acute liver failure did not affect long-term mortality. Clinical follow-up may be justified by the cause of the liver failure, but not by the liver failure itself."],"offsets":[[94,1488]]}],"entities":[{"id":"552","type":"Chemical","text":["paracetamol"],"offsets":[[53,64]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"553","type":"Disease","text":["acute liver failure"],"offsets":[[73,92]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"554","type":"Chemical","text":["paracetamol"],"offsets":[[153,164]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"555","type":"Disease","text":["acute liver failure"],"offsets":[[173,192]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"556","type":"Chemical","text":["paracetamol"],"offsets":[[234,245]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"557","type":"Disease","text":["acute liver 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{"id":"628","document_id":"20705401","passages":[{"id":"629","type":"title","text":["Serotonin 6 receptor gene is associated with methamphetamine-induced psychosis in a Japanese population."],"offsets":[[0,104]]},{"id":"630","type":"abstract","text":["BACKGROUND: Altered serotonergic neural transmission is hypothesized to be a susceptibility factor for psychotic disorders such as schizophrenia. The serotonin 6 (5-HT6) receptor is therapeutically targeted by several second generation antipsychotics, such as clozapine and olanzapine, and d-amphetamine-induced hyperactivity in rats is corrected with the use of a selective 5-HT6 receptor antagonist. In addition, the disrupted prepulse inhibition induced by d-amphetamine or phencyclidine was restored by 5-HT6 receptor antagonist in an animal study using rats. These animal models were considered to reflect the positive symptoms of schizophrenia, and the above evidence suggests that altered 5-HT6 receptors are involved in the pathophysiology of psychotic disorders. The symptoms of methamphetamine (METH)-induced psychosis are similar to those of paranoid type schizophrenia. Therefore, we conducted an analysis of the association of the 5-HT6 gene (HTR6) with METH-induced psychosis. METHOD: Using five tagging SNPs (rs6693503, rs1805054, rs4912138, rs3790757 and rs9659997), we conducted a genetic association analysis of case-control samples (197 METH-induced psychosis patients and 337 controls) in the Japanese population. The age and sex of the control subjects did not differ from those of the methamphetamine dependence patients. RESULTS: rs6693503 was associated with METH-induced psychosis patients in the allele\/genotype-wise analysis. Moreover, this association remained significant after Bonferroni correction. In the haplotype-wise analysis, we detected an association between two markers (rs6693503 and rs1805054) and three markers (rs6693503, rs1805054 and rs4912138) in HTR6 and METH-induced psychosis patients, respectively. CONCLUSION: HTR6 may play an important role in the pathophysiology of METH-induced psychosis in the Japanese population."],"offsets":[[105,1974]]}],"entities":[{"id":"631","type":"Chemical","text":["Serotonin"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"632","type":"Chemical","text":["methamphetamine"],"offsets":[[45,60]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"633","type":"Disease","text":["psychosis"],"offsets":[[69,78]],"normalized":[{"db_name":"MESH","db_id":"D011605"}]},{"id":"634","type":"Disease","text":["psychotic 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{"id":"746","document_id":"19105845","passages":[{"id":"747","type":"title","text":["Effect of increasing intraperitoneal infusion rates on bupropion hydrochloride-induced seizures in mice."],"offsets":[[0,104]]},{"id":"748","type":"abstract","text":["BACKGROUND: It is not known if there is a relationship between input rate and incidence of bupropion-induced seizures. This is important, since different controlled release formulations of bupropion release the active drug at different rates. METHODS: We investigated the effect of varying the intraperitoneal infusion rates of bupropion HCl 120 mg\/kg, a known convulsive dose 50 (CD50), on the incidence and severity of bupropion-induced convulsions in the Swiss albino mice. A total of 69 mice, approximately 7 weeks of age, and weighing 21.0 to 29.1 g were randomly assigned to bupropion HCl 120 mg\/kg treatment by intraperitoneal (IP) administration in 7 groups (9 to 10 animals per group). Bupropion HCl was infused through a surgically implanted IP dosing catheter with infusions in each group of 0 min, 15 min, 30 min, 60 min, 90 min, 120 min, and 240 min. The number, time of onset, duration and the intensity of the convulsions or absence of convulsions were recorded. RESULTS: The results showed that IP administration of bupropion HCl 120 mg\/kg by bolus injection induced convulsions in 6 out of 10 mice (60% of convulsing mice) in group 1. Logistic regression analysis revealed that infusion time was significant (p = 0.0004; odds ratio = 0.974) and increasing the IP infusion time of bupropion HCl 120 mg\/kg was associated with a 91% reduced odds of convulsions at infusion times of 15 to 90 min compared to bolus injection. Further increase in infusion time resulted in further reduction in the odds of convulsions to 99.8% reduction at 240 min. CONCLUSION: In conclusion, the demonstration of an inverse relationship between infusion time of a fixed and convulsive dose of bupropion and the risk of convulsions in a prospective study is novel."],"offsets":[[105,1863]]}],"entities":[{"id":"749","type":"Chemical","text":["bupropion hydrochloride"],"offsets":[[55,78]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"750","type":"Disease","text":["seizures"],"offsets":[[87,95]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"751","type":"Chemical","text":["bupropion"],"offsets":[[196,205]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"752","type":"Disease","text":["seizures"],"offsets":[[214,222]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"753","type":"Chemical","text":["bupropion"],"offsets":[[294,303]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"754","type":"Chemical","text":["bupropion 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{"id":"880","document_id":"18657397","passages":[{"id":"881","type":"title","text":["Detailed spectral profile analysis of penicillin-induced epileptiform activity in anesthetized rats."],"offsets":[[0,100]]},{"id":"882","type":"abstract","text":["Penicillin model is a widely used experimental model for epilepsy research. In the present study we aimed to portray a detailed spectral analysis of penicillin-induced epileptiform activity in comparison with basal brain activity in anesthetized Wistar rats. Male Wistar rats were anesthetized with i.p. urethane and connected to an electrocorticogram setup. After a short period of basal activity recording, epileptic focus was induced by injecting 400IU\/2 microl penicillin-G potassium into the left lateral ventricle while the cortical activity was continuously recorded. Basal activity, latent period and the penicillin-induced epileptiform activity periods were then analyzed using both conventional methods and spectral analysis. Spectral analyses were conducted by dividing the whole spectrum into different frequency bands including delta, theta (slow and fast), alpha-sigma, beta (1 and 2) and gamma (1 and 2) bands. Our results show that the most affected frequency bands were delta, theta, beta-2 and gamma-2 bands during the epileptiform activity and there were marked differences in terms of spectral densities between three investigated episodes (basal activity, latent period and epileptiform activity). Our results may help to analyze novel data obtained using similar experimental models and the simple analysis method described here can be used in similar studies to investigate the basic neuronal mechanism of this or other types of experimental epilepsies."],"offsets":[[101,1577]]}],"entities":[{"id":"883","type":"Chemical","text":["penicillin"],"offsets":[[38,48]],"normalized":[{"db_name":"MESH","db_id":"D010406"}]},{"id":"884","type":"Disease","text":["epileptiform activity"],"offsets":[[57,78]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"885","type":"Chemical","text":["Penicillin"],"offsets":[[101,111]],"normalized":[{"db_name":"MESH","db_id":"D010406"}]},{"id":"886","type":"Disease","text":["epilepsy"],"offsets":[[158,166]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"887","type":"Chemical","text":["penicillin"],"offsets":[[250,260]],"normalized":[{"db_name":"MESH","db_id":"D010406"}]},{"id":"888","type":"Disease","text":["epileptiform activity"],"offsets":[[269,290]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"889","type":"Chemical","text":["urethane"],"offsets":[[405,413]],"normalized":[{"db_name":"MESH","db_id":"D014520"}]},{"id":"890","type":"Disease","text":["epileptic"],"offsets":[[510,519]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"891","type":"Chemical","text":["penicillin-G potassium"],"offsets":[[566,588]],"normalized":[{"db_name":"MESH","db_id":"D010400"}]},{"id":"892","type":"Chemical","text":["penicillin"],"offsets":[[714,724]],"normalized":[{"db_name":"MESH","db_id":"D010406"}]},{"id":"893","type":"Disease","text":["epileptiform activity"],"offsets":[[733,754]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"894","type":"Disease","text":["epileptiform activity"],"offsets":[[1138,1159]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"895","type":"Disease","text":["epileptiform activity"],"offsets":[[1296,1317]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"896","type":"Disease","text":["epilepsies"],"offsets":[[1566,1576]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]}],"events":[],"coreferences":[],"relations":[{"id":"897","type":"CID","arg1_id":"891","arg2_id":"884","normalized":[]},{"id":"898","type":"CID","arg1_id":"891","arg2_id":"886","normalized":[]},{"id":"899","type":"CID","arg1_id":"891","arg2_id":"888","normalized":[]},{"id":"900","type":"CID","arg1_id":"891","arg2_id":"890","normalized":[]},{"id":"901","type":"CID","arg1_id":"891","arg2_id":"893","normalized":[]},{"id":"902","type":"CID","arg1_id":"891","arg2_id":"894","normalized":[]},{"id":"903","type":"CID","arg1_id":"891","arg2_id":"895","normalized":[]},{"id":"904","type":"CID","arg1_id":"891","arg2_id":"896","normalized":[]}]}
{"id":"905","document_id":"18363626","passages":[{"id":"906","type":"title","text":["High dose dexmedetomidine as the sole sedative for pediatric MRI."],"offsets":[[0,65]]},{"id":"907","type":"abstract","text":["OBJECTIVE: This large-scale retrospective review evaluates the sedation profile of dexmedetomidine. AIM: To determine the hemodynamic responses, efficacy and adverse events associated with the use of high dose dexmedetomidine as the sole sedative for magnetic resonance imaging (MRI) studies. BACKGROUND: Dexmedetomidine has been used at our institution since 2005 to provide sedation for pediatric radiological imaging studies. Over time, an effective protocol utilizing high dose dexmedetomidine as the sole sedative agent has evolved. METHODS\/MATERIALS: As part of the ongoing Quality Assurance process, data on all sedations are reviewed monthly and protocols modified as needed. Data were analyzed from all 747 consecutive patients who received dexmedetomidine for MRI sedation from April 2005 to April 2007. RESULTS: Since 2005, the 10-min loading dose of our dexmedetomidine protocol increased from 2 to 3 microg.kg(-1), and the infusion rate increased from 1 to 1.5 to 2 microg.kg(-1).h(-1). The current sedation protocol progressively increased the rate of successful sedation (able to complete the imaging study) when using dexmedetomidine alone from 91.8% to 97.6% (P = 0.009), reducing the requirement for adjuvant pentobarbital in the event of sedation failure with dexmedetomidine alone and decreased the mean recovery time by 10 min (P < 0.001). Although dexmedetomidine sedation was associated with a 16% incidence of bradycardia, all concomitant mean arterial blood pressures were within 20% of age-adjusted normal range and oxygen saturations were 95% or higher. CONCLUSION: Dexmedetomidine in high doses provides adequate sedation for pediatric MRI studies. While use of high dose dexmedetomidine is associated with decreases in heart rate and blood pressure outside the established 'awake' norms, this deviation is generally within 20% of norms, and is not associated with adverse sequelae. Dexmedetomidine is useful as the sole sedative for pediatric MRI."],"offsets":[[66,2042]]}],"entities":[{"id":"908","type":"Chemical","text":["dexmedetomidine"],"offsets":[[10,25]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"909","type":"Chemical","text":["dexmedetomidine"],"offsets":[[149,164]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"910","type":"Chemical","text":["dexmedetomidine"],"offsets":[[276,291]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"911","type":"Chemical","text":["Dexmedetomidine"],"offsets":[[371,386]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"912","type":"Chemical","text":["dexmedetomidine"],"offsets":[[548,563]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"913","type":"Chemical","text":["dexmedetomidine"],"offsets":[[816,831]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"914","type":"Chemical","text":["dexmedetomidine"],"offsets":[[932,947]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"915","type":"Chemical","text":["dexmedetomidine"],"offsets":[[1200,1215]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"916","type":"Chemical","text":["pentobarbital"],"offsets":[[1293,1306]],"normalized":[{"db_name":"MESH","db_id":"D010424"}]},{"id":"917","type":"Chemical","text":["dexmedetomidine"],"offsets":[[1345,1360]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"918","type":"Chemical","text":["dexmedetomidine"],"offsets":[[1436,1451]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"919","type":"Disease","text":["bradycardia"],"offsets":[[1500,1511]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"920","type":"Chemical","text":["oxygen"],"offsets":[[1608,1614]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"921","type":"Chemical","text":["Dexmedetomidine"],"offsets":[[1659,1674]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"922","type":"Chemical","text":["dexmedetomidine"],"offsets":[[1766,1781]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"923","type":"Chemical","text":["Dexmedetomidine"],"offsets":[[1977,1992]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]}],"events":[],"coreferences":[],"relations":[{"id":"924","type":"CID","arg1_id":"908","arg2_id":"919","normalized":[]},{"id":"925","type":"CID","arg1_id":"909","arg2_id":"919","normalized":[]},{"id":"926","type":"CID","arg1_id":"910","arg2_id":"919","normalized":[]},{"id":"927","type":"CID","arg1_id":"911","arg2_id":"919","normalized":[]},{"id":"928","type":"CID","arg1_id":"912","arg2_id":"919","normalized":[]},{"id":"929","type":"CID","arg1_id":"913","arg2_id":"919","normalized":[]},{"id":"930","type":"CID","arg1_id":"914","arg2_id":"919","normalized":[]},{"id":"931","type":"CID","arg1_id":"915","arg2_id":"919","normalized":[]},{"id":"932","type":"CID","arg1_id":"917","arg2_id":"919","normalized":[]},{"id":"933","type":"CID","arg1_id":"918","arg2_id":"919","normalized":[]},{"id":"934","type":"CID","arg1_id":"921","arg2_id":"919","normalized":[]},{"id":"935","type":"CID","arg1_id":"922","arg2_id":"919","normalized":[]},{"id":"936","type":"CID","arg1_id":"923","arg2_id":"919","normalized":[]}]}
{"id":"937","document_id":"16192988","passages":[{"id":"938","type":"title","text":["Methamphetamine causes alterations in the MAP kinase-related pathways in the brains of mice that display increased aggressiveness."],"offsets":[[0,130]]},{"id":"939","type":"abstract","text":["Aggressive behaviors have been reported in patients who suffer from some psychiatric disorders, and are common in methamphetamine (METH) abusers. Herein, we report that multiple (but not single) injections of METH significantly increased aggressiveness in male CD-1 mice. This increase in aggressiveness was not secondary to METH-induced hyperactivity. Analysis of protein expression using antibody microarrays and Western blotting revealed differential changes in MAP kinase-related pathways after multiple and single METH injections. There were statistically significant (p<0.05) decreases in MEK1, Erk2p, GSK3alpha, 14-3-3e, and MEK7 in the striata of mice after multiple injections of METH. MEK1 was significantly decreased also after a single injection of METH, but to a much lesser degree than after multiple injections of METH. In the frontal cortex, there was a statistically significant decrease in GSK3alpha after multiple (but not single) injections of METH. These findings suggest that alterations in MAP kinase-related pathways in the prefronto-striatal circuitries might be involved in the manifestation of aggressive behaviors in mice."],"offsets":[[131,1281]]}],"entities":[{"id":"940","type":"Chemical","text":["Methamphetamine"],"offsets":[[0,15]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"941","type":"Disease","text":["aggressiveness"],"offsets":[[115,129]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"942","type":"Disease","text":["Aggressive behaviors"],"offsets":[[131,151]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"943","type":"Disease","text":["psychiatric 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{"id":"1017","document_id":"16157917","passages":[{"id":"1018","type":"title","text":["Lamotrigine associated with exacerbation or de novo myoclonus in idiopathic generalized epilepsies."],"offsets":[[0,99]]},{"id":"1019","type":"abstract","text":["Five patients with idiopathic generalized epilepsies (IGE) treated with lamotrigine (LTG) experienced exacerbation or de novo appearance of myoclonic jerks (MJ). In three patients, LTG exacerbated MJ in a dose-dependent manner with early aggravation during titration. MJ disappeared when LTG dose was decreased by 25 to 50%. In two patients, LTG exacerbated MJ in a delayed but more severe manner, with myoclonic status that only ceased after LTG withdrawal."],"offsets":[[100,558]]}],"entities":[{"id":"1020","type":"Chemical","text":["Lamotrigine"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"C047781"}]},{"id":"1021","type":"Disease","text":["myoclonus"],"offsets":[[52,61]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"1022","type":"Disease","text":["idiopathic generalized epilepsies"],"offsets":[[65,98]],"normalized":[{"db_name":"MESH","db_id":"C562694"}]},{"id":"1023","type":"Disease","text":["idiopathic generalized epilepsies"],"offsets":[[119,152]],"normalized":[{"db_name":"MESH","db_id":"C562694"}]},{"id":"1024","type":"Disease","text":["IGE"],"offsets":[[154,157]],"normalized":[{"db_name":"MESH","db_id":"C562694"}]},{"id":"1025","type":"Chemical","text":["lamotrigine"],"offsets":[[172,183]],"normalized":[{"db_name":"MESH","db_id":"C047781"}]},{"id":"1026","type":"Chemical","text":["LTG"],"offsets":[[185,188]],"normalized":[{"db_name":"MESH","db_id":"C047781"}]},{"id":"1027","type":"Disease","text":["myoclonic jerks"],"offsets":[[240,255]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"1028","type":"Disease","text":["MJ"],"offsets":[[257,259]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"1029","type":"Chemical","text":["LTG"],"offsets":[[281,284]],"normalized":[{"db_name":"MESH","db_id":"C047781"}]},{"id":"1030","type":"Disease","text":["MJ"],"offsets":[[297,299]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"1031","type":"Disease","text":["MJ"],"offsets":[[368,370]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"1032","type":"Chemical","text":["LTG"],"offsets":[[388,391]],"normalized":[{"db_name":"MESH","db_id":"C047781"}]},{"id":"1033","type":"Chemical","text":["LTG"],"offsets":[[442,445]],"normalized":[{"db_name":"MESH","db_id":"C047781"}]},{"id":"1034","type":"Disease","text":["MJ"],"offsets":[[458,460]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"1035","type":"Disease","text":["myoclonic status"],"offsets":[[503,519]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"1036","type":"Chemical","text":["LTG"],"offsets":[[543,546]],"normalized":[{"db_name":"MESH","db_id":"C047781"}]}],"events":[],"coreferences":[],"relations":[{"id":"1037","type":"CID","arg1_id":"1020","arg2_id":"1021","normalized":[]},{"id":"1038","type":"CID","arg1_id":"1020","arg2_id":"1027","normalized":[]},{"id":"1039","type":"CID","arg1_id":"1020","arg2_id":"1028","normalized":[]},{"id":"1040","type":"CID","arg1_id":"1020","arg2_id":"1030","normalized":[]},{"id":"1041","type":"CID","arg1_id":"1020","arg2_id":"1031","normalized":[]},{"id":"1042","type":"CID","arg1_id":"1020","arg2_id":"1034","normalized":[]},{"id":"1043","type":"CID","arg1_id":"1020","arg2_id":"1035","normalized":[]},{"id":"1044","type":"CID","arg1_id":"1025","arg2_id":"1021","normalized":[]},{"id":"1045","type":"CID","arg1_id":"1025","arg2_id":"1027","normalized":[]},{"id":"1046","type":"CID","arg1_id":"1025","arg2_id":"1028","normalized":[]},{"id":"1047","type":"CID","arg1_id":"1025","arg2_id":"1030","normalized":[]},{"id":"1048","type":"CID","arg1_id":"1025","arg2_id":"1031","normalized":[]},{"id":"1049","type":"CID","arg1_id":"1025","arg2_id":"1034","normalized":[]},{"id":"1050","type":"CID","arg1_id":"1025","arg2_id":"1035","normalized":[]},{"id":"1051","type":"CID","arg1_id":"1026","arg2_id":"1021","normalized":[]},{"id":"1052","type":"CID","arg1_id":"1026","arg2_id":"1027","normalized":[]},{"id":"1053","type":"CID","arg1_id":"1026","arg2_id":"1028","normalized":[]},{"id":"1054","type":"CID","arg1_id":"1026","arg2_id":"1030","normalized":[]},{"id":"1055","type":"CID","arg1_id":"1026","arg2_id":"1031","normalized":[]},{"id":"1056","type":"CID","arg1_id":"1026","arg2_id":"1034","normalized":[]},{"id":"1057","type":"CID","arg1_id":"1026","arg2_id":"1035","normalized":[]},{"id":"1058","type":"CID","arg1_id":"1029","arg2_id":"1021","normalized":[]},{"id":"1059","type":"CID","arg1_id":"1029","arg2_id":"1027","normalized":[]},{"id":"1060","type":"CID","arg1_id":"1029","arg2_id":"1028","normalized":[]},{"id":"1061","type":"CID","arg1_id":"1029","arg2_id":"1030","normalized":[]},{"id":"1062","type":"CID","arg1_id":"1029","arg2_id":"1031","normalized":[]},{"id":"1063","type":"CID","arg1_id":"1029","arg2_id":"1034","normalized":[]},{"id":"1064","type":"CID","arg1_id":"1029","arg2_id":"1035","normalized":[]},{"id":"1065","type":"CID","arg1_id":"1032","arg2_id":"1021","normalized":[]},{"id":"1066","type":"CID","arg1_id":"1032","arg2_id":"1027","normalized":[]},{"id":"1067","type":"CID","arg1_id":"1032","arg2_id":"1028","normalized":[]},{"id":"1068","type":"CID","arg1_id":"1032","arg2_id":"1030","normalized":[]},{"id":"1069","type":"CID","arg1_id":"1032","arg2_id":"1031","normalized":[]},{"id":"1070","type":"CID","arg1_id":"1032","arg2_id":"1034","normalized":[]},{"id":"1071","type":"CID","arg1_id":"1032","arg2_id":"1035","normalized":[]},{"id":"1072","type":"CID","arg1_id":"1033","arg2_id":"1021","normalized":[]},{"id":"1073","type":"CID","arg1_id":"1033","arg2_id":"1027","normalized":[]},{"id":"1074","type":"CID","arg1_id":"1033","arg2_id":"1028","normalized":[]},{"id":"1075","type":"CID","arg1_id":"1033","arg2_id":"1030","normalized":[]},{"id":"1076","type":"CID","arg1_id":"1033","arg2_id":"1031","normalized":[]},{"id":"1077","type":"CID","arg1_id":"1033","arg2_id":"1034","normalized":[]},{"id":"1078","type":"CID","arg1_id":"1033","arg2_id":"1035","normalized":[]},{"id":"1079","type":"CID","arg1_id":"1036","arg2_id":"1021","normalized":[]},{"id":"1080","type":"CID","arg1_id":"1036","arg2_id":"1027","normalized":[]},{"id":"1081","type":"CID","arg1_id":"1036","arg2_id":"1028","normalized":[]},{"id":"1082","type":"CID","arg1_id":"1036","arg2_id":"1030","normalized":[]},{"id":"1083","type":"CID","arg1_id":"1036","arg2_id":"1031","normalized":[]},{"id":"1084","type":"CID","arg1_id":"1036","arg2_id":"1034","normalized":[]},{"id":"1085","type":"CID","arg1_id":"1036","arg2_id":"1035","normalized":[]}]}
{"id":"1086","document_id":"16116131","passages":[{"id":"1087","type":"title","text":["rTMS of supplementary motor area modulates therapy-induced dyskinesias in Parkinson disease."],"offsets":[[0,92]]},{"id":"1088","type":"abstract","text":["The neural mechanisms and circuitry involved in levodopa-induced dyskinesia are unclear. Using repetitive transcranial magnetic stimulation (rTMS) over the supplementary motor area (SMA) in a group of patients with advanced Parkinson disease, the authors investigated whether modulation of SMA excitability may result in a modification of a dyskinetic state induced by continuous apomorphine infusion. rTMS at 1 Hz was observed to markedly reduce drug-induced dyskinesias, whereas 5-Hz rTMS induced a slight but not significant increase."],"offsets":[[93,630]]}],"entities":[{"id":"1089","type":"Disease","text":["dyskinesias"],"offsets":[[59,70]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"1090","type":"Disease","text":["Parkinson disease"],"offsets":[[74,91]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"1091","type":"Chemical","text":["levodopa"],"offsets":[[141,149]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"1092","type":"Disease","text":["dyskinesia"],"offsets":[[158,168]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"1093","type":"Disease","text":["Parkinson disease"],"offsets":[[317,334]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"1094","type":"Disease","text":["dyskinetic"],"offsets":[[434,444]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"1095","type":"Chemical","text":["apomorphine"],"offsets":[[473,484]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"1096","type":"Disease","text":["drug-induced dyskinesias"],"offsets":[[540,564]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]}],"events":[],"coreferences":[],"relations":[{"id":"1097","type":"CID","arg1_id":"1091","arg2_id":"1089","normalized":[]},{"id":"1098","type":"CID","arg1_id":"1091","arg2_id":"1092","normalized":[]},{"id":"1099","type":"CID","arg1_id":"1091","arg2_id":"1094","normalized":[]},{"id":"1100","type":"CID","arg1_id":"1091","arg2_id":"1096","normalized":[]}]}
{"id":"1101","document_id":"15930398","passages":[{"id":"1102","type":"title","text":["Assessment of the onset and persistence of amnesia during procedural sedation with propofol."],"offsets":[[0,92]]},{"id":"1103","type":"abstract","text":["OBJECTIVES: To assess patients' ability to repeat and recall words presented to them while undergoing procedural sedation with propofol, and correlate their recall with their level of awareness as measured by bispectral index (BIS) monitoring. METHODS: This was a prospective, single-intervention study of consenting adult patients undergoing procedural sedation with propofol between December 28, 2002, and October 31, 2003. BIS monitoring was initiated starting 3 minutes before the procedure and continuing until the patient had regained baseline mental status. At 1-minute intervals during the procedural sedation, until the patient regained baseline mental status at the end of the procedure, a word from a standardized list was read aloud, and the patient was asked to immediately repeat the word to the investigator. The BIS score at the time the word was read and the patient's ability to repeat the word were recorded. After the procedure, the patient was asked to state all of the words from the list that he or she could recall, and to identify the last word recalled from prior to the start of the procedure and the first word recalled from after the procedure was completed. RESULTS: Seventy-five consenting patients were enrolled; one patient was excluded from data analysis for a protocol violation. No serious adverse events were noted during the procedural sedations. The mean (+\/-standard deviation) time of data collection was 16.4 minutes (+\/-7.1; range 5 to 34 minutes). The mean initial (preprocedure) BIS score was 97.1 (+\/-2.3; range 92 to 99). The mean lowest BIS score occurring during these procedural sedations was 66.9 (+\/-14.4; range 33 to 91). The mean lowest BIS score corresponding to the ability of the patient to immediately repeat words read from the list was 77.1 (95% CI = 74.3 to 80.0). The mean highest BIS score corresponding to the inability to repeat words was 81.5 (95% CI = 78.1 to 84.8). The mean BIS score corresponding to the last word recalled from prior to the initiation of the sedation was 96.7 (+\/-2.4; range 84 to 98). The mean BIS score corresponding to the first word recalled after the procedure was completed was 91.2 (95% CI = 88.1 to 94.3). All patients recalled at least one word that had been read to them during the protocol. The mean lowest BIS score for any recalled word was 91.5 (+\/-11.1; range 79 to 98), and no words were recalled when the corresponding BIS score was less than 90. CONCLUSIONS: There is a range of BIS scores during which sedated patients are able to repeat words read to them but are not able to subsequently recall these words. Furthermore, patients had no recall of words repeated prior to procedural sedation in BIS ranges associated with recall after procedural sedation, suggestive of retrograde amnesia."],"offsets":[[93,2889]]}],"entities":[{"id":"1104","type":"Disease","text":["amnesia"],"offsets":[[43,50]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"1105","type":"Chemical","text":["propofol"],"offsets":[[83,91]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"1106","type":"Chemical","text":["propofol"],"offsets":[[220,228]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"1107","type":"Chemical","text":["propofol"],"offsets":[[461,469]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"1108","type":"Disease","text":["inability to repeat words"],"offsets":[[1967,1992]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"1109","type":"Disease","text":["retrograde amnesia"],"offsets":[[2870,2888]],"normalized":[{"db_name":"MESH","db_id":"D000648"}]}],"events":[],"coreferences":[],"relations":[{"id":"1110","type":"CID","arg1_id":"1105","arg2_id":"1104","normalized":[]},{"id":"1111","type":"CID","arg1_id":"1105","arg2_id":"1108","normalized":[]},{"id":"1112","type":"CID","arg1_id":"1106","arg2_id":"1104","normalized":[]},{"id":"1113","type":"CID","arg1_id":"1106","arg2_id":"1108","normalized":[]},{"id":"1114","type":"CID","arg1_id":"1107","arg2_id":"1104","normalized":[]},{"id":"1115","type":"CID","arg1_id":"1107","arg2_id":"1108","normalized":[]}]}
{"id":"1116","document_id":"15867025","passages":[{"id":"1117","type":"title","text":["Assessment of perinatal hepatitis B and rubella prevention in New Hampshire delivery hospitals."],"offsets":[[0,95]]},{"id":"1118","type":"abstract","text":["OBJECTIVE: To evaluate current performance on recommended perinatal hepatitis B and rubella prevention practices in New Hampshire. METHODS: Data were extracted from 2021 paired mother-infant records for the year 2000 birth cohort in New Hampshire's 25 delivery hospitals. Assessment was done on the following: prenatal screening for hepatitis B and rubella, administration of the hepatitis B vaccine birth dose to all infants, administration of hepatitis B immune globulin to infants who were born to hepatitis B surface antigen-positive mothers, rubella immunity, and administration of in-hospital postpartum rubella vaccine to rubella nonimmune women. RESULTS: Prenatal screening rates for hepatitis B (98.8%) and rubella (99.4%) were high. Hepatitis B vaccine birth dose was administered to 76.2% of all infants. All infants who were born to hepatitis B surface antigen-positive mothers also received hepatitis B immune globulin. Multivariate logistic regression showed that the month of delivery and infant birth weight were independent predictors of hepatitis B vaccination. The proportion of infants who were vaccinated in January and February 2000 (48.5% and 67.5%, respectively) was less than any other months, whereas the proportion who were vaccinated in December 2000 (88.2%) was the highest. Women who were born between 1971 and 1975 had the highest rate of rubella nonimmunity (9.5%). In-hospital postpartum rubella vaccine administration was documented for 75.6% of nonimmune women. CONCLUSION: This study documents good compliance in New Hampshire's birthing hospitals with national guidelines for perinatal hepatitis B and rubella prevention and highlights potential areas for improvement."],"offsets":[[96,1801]]}],"entities":[{"id":"1119","type":"Disease","text":["hepatitis B"],"offsets":[[24,35]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"1120","type":"Disease","text":["rubella"],"offsets":[[40,47]],"normalized":[{"db_name":"MESH","db_id":"D012409"}]},{"id":"1121","type":"Disease","text":["hepatitis B"],"offsets":[[164,175]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"1122","type":"Disease","text":["rubella"],"offsets":[[180,187]],"normalized":[{"db_name":"MESH","db_id":"D012409"}]},{"id":"1123","type":"Disease","text":["hepatitis B"],"offsets":[[429,440]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"1124","type":"Disease","text":["rubella"],"offsets":[[445,452]],"normalized":[{"db_name":"MESH","db_id":"D012409"}]},{"id":"1125","type":"Disease","text":["hepatitis B"],"offsets":[[476,487]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"1126","type":"Disease","text":["hepatitis B"],"offsets":[[541,552]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"1127","type":"Chemical","text":["hepatitis B surface antigen"],"offsets":[[597,624]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"1128","type":"Disease","text":["rubella"],"offsets":[[643,650]],"normalized":[{"db_name":"MESH","db_id":"D012409"}]},{"id":"1129","type":"Disease","text":["rubella"],"offsets":[[706,713]],"normalized":[{"db_name":"MESH","db_id":"D012409"}]},{"id":"1130","type":"Disease","text":["rubella"],"offsets":[[725,732]],"normalized":[{"db_name":"MESH","db_id":"D012409"}]},{"id":"1131","type":"Disease","text":["hepatitis B"],"offsets":[[788,799]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"1132","type":"Disease","text":["rubella"],"offsets":[[812,819]],"normalized":[{"db_name":"MESH","db_id":"D012409"}]},{"id":"1133","type":"Disease","text":["Hepatitis B"],"offsets":[[839,850]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"1134","type":"Chemical","text":["hepatitis B surface antigen"],"offsets":[[941,968]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"1135","type":"Disease","text":["hepatitis B"],"offsets":[[1000,1011]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"1136","type":"Disease","text":["hepatitis B"],"offsets":[[1151,1162]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"1137","type":"Disease","text":["rubella"],"offsets":[[1466,1473]],"normalized":[{"db_name":"MESH","db_id":"D012409"}]},{"id":"1138","type":"Disease","text":["rubella"],"offsets":[[1517,1524]],"normalized":[{"db_name":"MESH","db_id":"D012409"}]},{"id":"1139","type":"Disease","text":["hepatitis B"],"offsets":[[1719,1730]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"1140","type":"Disease","text":["rubella"],"offsets":[[1735,1742]],"normalized":[{"db_name":"MESH","db_id":"D012409"}]}],"events":[],"coreferences":[],"relations":[{"id":"1141","type":"CID","arg1_id":"1127","arg2_id":"1119","normalized":[]},{"id":"1142","type":"CID","arg1_id":"1127","arg2_id":"1121","normalized":[]},{"id":"1143","type":"CID","arg1_id":"1127","arg2_id":"1123","normalized":[]},{"id":"1144","type":"CID","arg1_id":"1127","arg2_id":"1125","normalized":[]},{"id":"1145","type":"CID","arg1_id":"1127","arg2_id":"1126","normalized":[]},{"id":"1146","type":"CID","arg1_id":"1127","arg2_id":"1131","normalized":[]},{"id":"1147","type":"CID","arg1_id":"1127","arg2_id":"1133","normalized":[]},{"id":"1148","type":"CID","arg1_id":"1127","arg2_id":"1135","normalized":[]},{"id":"1149","type":"CID","arg1_id":"1127","arg2_id":"1136","normalized":[]},{"id":"1150","type":"CID","arg1_id":"1127","arg2_id":"1139","normalized":[]},{"id":"1151","type":"CID","arg1_id":"1134","arg2_id":"1119","normalized":[]},{"id":"1152","type":"CID","arg1_id":"1134","arg2_id":"1121","normalized":[]},{"id":"1153","type":"CID","arg1_id":"1134","arg2_id":"1123","normalized":[]},{"id":"1154","type":"CID","arg1_id":"1134","arg2_id":"1125","normalized":[]},{"id":"1155","type":"CID","arg1_id":"1134","arg2_id":"1126","normalized":[]},{"id":"1156","type":"CID","arg1_id":"1134","arg2_id":"1131","normalized":[]},{"id":"1157","type":"CID","arg1_id":"1134","arg2_id":"1133","normalized":[]},{"id":"1158","type":"CID","arg1_id":"1134","arg2_id":"1135","normalized":[]},{"id":"1159","type":"CID","arg1_id":"1134","arg2_id":"1136","normalized":[]},{"id":"1160","type":"CID","arg1_id":"1134","arg2_id":"1139","normalized":[]}]}
{"id":"1161","document_id":"14975762","passages":[{"id":"1162","type":"title","text":["Expression of p300 protects cardiac myocytes from apoptosis in vivo."],"offsets":[[0,68]]},{"id":"1163","type":"abstract","text":["Doxorubicin is an anti-tumor agent that represses cardiac-specific gene expression and induces myocardial cell apoptosis. Doxorubicin depletes cardiac p300, a transcriptional coactivator that is required for the maintenance of the differentiated phenotype of cardiac myocytes. However, the role of p300 in protection against doxorubicin-induced apoptosis is unknown. Transgenic mice overexpressing p300 in the heart and wild-type mice were subjected to doxorubicin treatment. Compared with wild-type mice, transgenic mice exhibited higher survival rate as well as more preserved left ventricular function and cardiac expression of alpha-sarcomeric actin. Doxorubicin induced myocardial cell apoptosis in wild-type mice but not in transgenic mice. Expression of p300 increased the cardiac level of bcl-2 and mdm-2, but not that of p53 or other members of the bcl-2 family. These findings demonstrate that overexpression of p300 protects cardiac myocytes from doxorubicin-induced apoptosis and reduces the extent of acute heart failure in adult mice in vivo."],"offsets":[[69,1125]]}],"entities":[{"id":"1164","type":"Chemical","text":["Doxorubicin"],"offsets":[[69,80]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1165","type":"Disease","text":["tumor"],"offsets":[[92,97]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"1166","type":"Chemical","text":["Doxorubicin"],"offsets":[[191,202]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1167","type":"Chemical","text":["doxorubicin"],"offsets":[[394,405]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1168","type":"Chemical","text":["doxorubicin"],"offsets":[[522,533]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1169","type":"Chemical","text":["Doxorubicin"],"offsets":[[724,735]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1170","type":"Chemical","text":["doxorubicin"],"offsets":[[1027,1038]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1171","type":"Disease","text":["heart failure"],"offsets":[[1089,1102]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]}],"events":[],"coreferences":[],"relations":[{"id":"1172","type":"CID","arg1_id":"1164","arg2_id":"1171","normalized":[]},{"id":"1173","type":"CID","arg1_id":"1166","arg2_id":"1171","normalized":[]},{"id":"1174","type":"CID","arg1_id":"1167","arg2_id":"1171","normalized":[]},{"id":"1175","type":"CID","arg1_id":"1168","arg2_id":"1171","normalized":[]},{"id":"1176","type":"CID","arg1_id":"1169","arg2_id":"1171","normalized":[]},{"id":"1177","type":"CID","arg1_id":"1170","arg2_id":"1171","normalized":[]}]}
{"id":"1178","document_id":"14736955","passages":[{"id":"1179","type":"title","text":["Mitochondrial DNA and its respiratory chain products are defective in doxorubicin nephrosis."],"offsets":[[0,92]]},{"id":"1180","type":"abstract","text":["BACKGROUND: Doxorubicin induces a self-perpetuating nephropathy characterized by early glomerular and late-onset tubular lesions in rats. We investigated the potential role of mitochondrial injury in the onset of these lesions. METHODS: Rats were treated with intravenous doxorubicin (1 mg kg(-1) week(-1)) for 7 weeks and were sacrificed either 1 week ('short-term') or 30 weeks ('long-term') following the last dose. Additional rats received a single dose either 6 days or 2 h prior to euthanasia. All rats were killed at 48 weeks of age. Glomerular and tubular injury was monitored and correlated to the activity or expression of respiratory chain components. Finally, we quantified both nuclear and mitochondrial DNA (mtDNA) as well as superoxide production and the 4834 base pair 'common' mtDNA deletion. RESULTS: The 'long-term' group had significant glomerular and tubular lesions, depressed activities of mtDNA-encoded NADH dehydrogenase and cytochrome-c oxidase (COX) and increased citrate synthase activity. In addition, expression of the mtDNA-encoded COX subunit I was reduced and mtDNA levels were decreased. In 'short-term' rats, there were fewer tubular lesions, but similar numbers of glomerular lesions activity. Among all animals, glomerular and tubular injury were inversely correlated with mtDNA levels, mtDNA-encoded respiratory chain activities and with the expression of the mtDNA-encoded respiratory chain subunit COX-I. Injury was positively correlated with superoxide production and the activities of nucleus-encoded mitochondrial or cytoplasmic enzymes. Kidneys from the 'long-term' group showed more mtDNA deletions than in 'short-term' animals and these were not observed in the other groups. CONCLUSIONS: These results suggest an important role for quantitative and qualitative mtDNA alterations through the reduction of mtDNA-encoded respiratory chain function and induction of superoxide in doxorubicin-induced renal lesions."],"offsets":[[93,2050]]}],"entities":[{"id":"1181","type":"Chemical","text":["doxorubicin"],"offsets":[[70,81]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1182","type":"Disease","text":["nephrosis"],"offsets":[[82,91]],"normalized":[{"db_name":"MESH","db_id":"D009401"}]},{"id":"1183","type":"Chemical","text":["Doxorubicin"],"offsets":[[105,116]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1184","type":"Disease","text":["nephropathy"],"offsets":[[145,156]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"1185","type":"Disease","text":["glomerular and late-onset tubular lesions"],"offsets":[[180,221]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"1186","type":"Disease","text":["mitochondrial injury"],"offsets":[[269,289]],"normalized":[{"db_name":"MESH","db_id":"D028361"}]},{"id":"1187","type":"Chemical","text":["doxorubicin"],"offsets":[[365,376]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1188","type":"Disease","text":["Glomerular and tubular injury"],"offsets":[[634,663]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"1189","type":"Chemical","text":["superoxide"],"offsets":[[833,843]],"normalized":[{"db_name":"MESH","db_id":"D013481"}]},{"id":"1190","type":"Disease","text":["glomerular and tubular lesions"],"offsets":[[950,980]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"1191","type":"Chemical","text":["citrate"],"offsets":[[1084,1091]],"normalized":[{"db_name":"MESH","db_id":"C102006"}]},{"id":"1192","type":"Disease","text":["tubular lesions"],"offsets":[[1254,1269]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"1193","type":"Disease","text":["glomerular lesions"],"offsets":[[1294,1312]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"1194","type":"Disease","text":["glomerular and tubular injury"],"offsets":[[1342,1371]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"1195","type":"Chemical","text":["superoxide"],"offsets":[[1576,1586]],"normalized":[{"db_name":"MESH","db_id":"D013481"}]},{"id":"1196","type":"Chemical","text":["superoxide"],"offsets":[[2002,2012]],"normalized":[{"db_name":"MESH","db_id":"D013481"}]},{"id":"1197","type":"Chemical","text":["doxorubicin"],"offsets":[[2016,2027]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1198","type":"Disease","text":["renal lesions"],"offsets":[[2036,2049]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"1199","type":"CID","arg1_id":"1181","arg2_id":"1182","normalized":[]},{"id":"1200","type":"CID","arg1_id":"1183","arg2_id":"1182","normalized":[]},{"id":"1201","type":"CID","arg1_id":"1187","arg2_id":"1182","normalized":[]},{"id":"1202","type":"CID","arg1_id":"1197","arg2_id":"1182","normalized":[]}]}
{"id":"1203","document_id":"11573852","passages":[{"id":"1204","type":"title","text":["Amphotericin B-induced seizures in a patient with AIDS."],"offsets":[[0,55]]},{"id":"1205","type":"abstract","text":["OBJECTIVE: To report a case of multiple episodes of seizure activity in an AIDS patent following amphotericin B infusion. CASE SUMMARY: A 46-year-old African-American man experienced recurrent grand mal seizures during intravenous infusion of amphotericin B, then petit mal seizures as the infusion was stopped and the drug concentrations decreased with time. The patients concurrent medications included didanosine, hydroxyzine, promethazine, hydrocortisone, and prochlorperazine. Despite administration of phenytoin and lorazepam, the seizures persisted and occurred only during amphotercin B administration. DISCUSSION: AIDS and cryptococcal meningitis, both of which the patient had, can potentially cause seizures. The patient had a history of alcohol abuse; alcohol intake as well as withdrawal can also cause seizures. Didanosine also has a potential for inducing seizures. However, these other potential causes of seizure were ruled out. The time course of events suggested that amphotericin B was the cause of the seizures in this AIDS patient. CONCLUSIONS: Amphotericin B seems to be the probable cause of the seizures. To date, only three cases of seizures associated with amphotericin B have been reported in the literature, but healthcare providers should be aware of the potential for this rare adverse effect."],"offsets":[[56,1380]]}],"entities":[{"id":"1206","type":"Chemical","text":["Amphotericin B"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"1207","type":"Disease","text":["seizures"],"offsets":[[23,31]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"1208","type":"Disease","text":["AIDS"],"offsets":[[50,54]],"normalized":[{"db_name":"MESH","db_id":"D000163"}]},{"id":"1209","type":"Disease","text":["seizure"],"offsets":[[108,115]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"1210","type":"Disease","text":["AIDS"],"offsets":[[131,135]],"normalized":[{"db_name":"MESH","db_id":"D000163"}]},{"id":"1211","type":"Chemical","text":["amphotericin B"],"offsets":[[153,167]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"1212","type":"Disease","text":["grand mal seizures"],"offsets":[[249,267]],"normalized":[{"db_name":"MESH","db_id":"D004830"}]},{"id":"1213","type":"Chemical","text":["amphotericin B"],"offsets":[[299,313]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"1214","type":"Disease","text":["seizures"],"offsets":[[330,338]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"1215","type":"Chemical","text":["didanosine"],"offsets":[[461,471]],"normalized":[{"db_name":"MESH","db_id":"D016049"}]},{"id":"1216","type":"Chemical","text":["hydroxyzine"],"offsets":[[473,484]],"normalized":[{"db_name":"MESH","db_id":"D006919"}]},{"id":"1217","type":"Chemical","text":["promethazine"],"offsets":[[486,498]],"normalized":[{"db_name":"MESH","db_id":"D011398"}]},{"id":"1218","type":"Chemical","text":["hydrocortisone"],"offsets":[[500,514]],"normalized":[{"db_name":"MESH","db_id":"D006854"}]},{"id":"1219","type":"Chemical","text":["prochlorperazine"],"offsets":[[520,536]],"normalized":[{"db_name":"MESH","db_id":"D011346"}]},{"id":"1220","type":"Chemical","text":["phenytoin"],"offsets":[[564,573]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"1221","type":"Chemical","text":["lorazepam"],"offsets":[[578,587]],"normalized":[{"db_name":"MESH","db_id":"D008140"}]},{"id":"1222","type":"Disease","text":["seizures"],"offsets":[[593,601]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"1223","type":"Chemical","text":["amphotercin B"],"offsets":[[637,650]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"1224","type":"Disease","text":["AIDS"],"offsets":[[679,683]],"normalized":[{"db_name":"MESH","db_id":"D000163"}]},{"id":"1225","type":"Disease","text":["cryptococcal meningitis"],"offsets":[[688,711]],"normalized":[{"db_name":"MESH","db_id":"D016919"}]},{"id":"1226","type":"Disease","text":["seizures"],"offsets":[[766,774]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"1227","type":"Disease","text":["alcohol abuse"],"offsets":[[805,818]],"normalized":[{"db_name":"MESH","db_id":"D000437"}]},{"id":"1228","type":"Chemical","text":["alcohol"],"offsets":[[820,827]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"1229","type":"Disease","text":["seizures"],"offsets":[[872,880]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"1230","type":"Chemical","text":["Didanosine"],"offsets":[[882,892]],"normalized":[{"db_name":"MESH","db_id":"D016049"}]},{"id":"1231","type":"Disease","text":["seizures"],"offsets":[[927,935]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"1232","type":"Disease","text":["seizure"],"offsets":[[978,985]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"1233","type":"Chemical","text":["amphotericin B"],"offsets":[[1043,1057]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"1234","type":"Disease","text":["seizures"],"offsets":[[1079,1087]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"1235","type":"Disease","text":["AIDS"],"offsets":[[1096,1100]],"normalized":[{"db_name":"MESH","db_id":"D000163"}]},{"id":"1236","type":"Chemical","text":["Amphotericin B"],"offsets":[[1123,1137]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"1237","type":"Disease","text":["seizures"],"offsets":[[1176,1184]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"1238","type":"Disease","text":["seizures"],"offsets":[[1215,1223]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"1239","type":"Chemical","text":["amphotericin 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{"id":"1317","document_id":"9875685","passages":[{"id":"1318","type":"title","text":["Therapeutic drug monitoring of tobramycin: once-daily versus twice-daily dosage schedules."],"offsets":[[0,90]]},{"id":"1319","type":"abstract","text":["OBJECTIVE: To evaluate the effect of dosage regimen (once-daily vs. twice-daily) of tobramicyn on steady-state serum concentrations and toxicity. MATERIALS AND METHODS: Patients undergoing treatment with i.v. tobramycin (4 mg\/kg\/day) were randomised to two groups. Group OD (n = 22) received a once-daily dose of tobramycin and group TD (n = 21) received the same dose divided into two doses daily. Tobramycin serum concentrations (peak and trough) were measured by enzyme multiplied immunoassay. The renal and auditory functions of the patients were monitored before, during and immediately after treatment. RESULTS: The two groups were comparable with respect to sex, age, body weight and renal function. No statistically significant differences were found in mean daily dose, duration of treatment, or cumulative dose. Trough concentrations were < 2 g\/ml in the two groups (100%). Peak concentrations were > 6 microg\/ml in 100% of the OD group and in 67% of the TD group (P< 0.01). Mean peak concentrations were markedly different: 11.00+\/-2.89 microg\/ml in OD vs. 6.53+\/-1.45 microg\/ml in TD (P< 0.01). The pharmacokinetics parameters were: Ke, (0.15+\/-0.03\/h in OD vs. 0.24+\/-0.06\/h in TD), t1\/2, (4.95+\/-1.41 h in OD vs. 3.07+\/-0.71 h in TD), Vd (0.35+\/-0.11 l\/kg in OD vs. 0.33+\/-0.09 l\/kg in TD), Cl (0.86+\/-0.29 ml\/min\/kg in OD vs. 1.28+\/-0.33 ml\/min\/kg in TD). Increased serum creatinine was observed in 73% of patients in OD versus 57% of patients in TD, without evidence of nephrotoxicity. In TD group, three patients developed decreased auditory function, of which one presented with an auditory loss of -30 dB, whereas in the OD group only one patient presented decreased auditory function. CONCLUSION: This small study suggests that a once-daily dosing regimen of tobramycin is at least as effective as and is no more and possibly less toxic than the twice-daily regimen. Using a single-dose therapy, peak concentration determination is not necessary, only trough samples should be monitored to ensure levels below 2 microg\/ml."],"offsets":[[91,2133]]}],"entities":[{"id":"1320","type":"Chemical","text":["tobramycin"],"offsets":[[31,41]],"normalized":[{"db_name":"MESH","db_id":"D014031"}]},{"id":"1321","type":"Chemical","text":["tobramicyn"],"offsets":[[175,185]],"normalized":[{"db_name":"MESH","db_id":"D014031"}]},{"id":"1322","type":"Disease","text":["toxicity"],"offsets":[[227,235]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"1323","type":"Chemical","text":["tobramycin"],"offsets":[[300,310]],"normalized":[{"db_name":"MESH","db_id":"D014031"}]},{"id":"1324","type":"Chemical","text":["tobramycin"],"offsets":[[404,414]],"normalized":[{"db_name":"MESH","db_id":"D014031"}]},{"id":"1325","type":"Chemical","text":["Tobramycin"],"offsets":[[490,500]],"normalized":[{"db_name":"MESH","db_id":"D014031"}]},{"id":"1326","type":"Chemical","text":["creatinine"],"offsets":[[1478,1488]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"1327","type":"Disease","text":["nephrotoxicity"],"offsets":[[1577,1591]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"1328","type":"Disease","text":["decreased auditory function"],"offsets":[[1631,1658]],"normalized":[{"db_name":"MESH","db_id":"D034381"}]},{"id":"1329","type":"Disease","text":["auditory loss"],"offsets":[[1691,1704]],"normalized":[{"db_name":"MESH","db_id":"D034381"}]},{"id":"1330","type":"Disease","text":["decreased auditory function"],"offsets":[[1767,1794]],"normalized":[{"db_name":"MESH","db_id":"D034381"}]},{"id":"1331","type":"Chemical","text":["tobramycin"],"offsets":[[1870,1880]],"normalized":[{"db_name":"MESH","db_id":"D014031"}]}],"events":[],"coreferences":[],"relations":[{"id":"1332","type":"CID","arg1_id":"1320","arg2_id":"1328","normalized":[]},{"id":"1333","type":"CID","arg1_id":"1320","arg2_id":"1329","normalized":[]},{"id":"1334","type":"CID","arg1_id":"1320","arg2_id":"1330","normalized":[]},{"id":"1335","type":"CID","arg1_id":"1321","arg2_id":"1328","normalized":[]},{"id":"1336","type":"CID","arg1_id":"1321","arg2_id":"1329","normalized":[]},{"id":"1337","type":"CID","arg1_id":"1321","arg2_id":"1330","normalized":[]},{"id":"1338","type":"CID","arg1_id":"1323","arg2_id":"1328","normalized":[]},{"id":"1339","type":"CID","arg1_id":"1323","arg2_id":"1329","normalized":[]},{"id":"1340","type":"CID","arg1_id":"1323","arg2_id":"1330","normalized":[]},{"id":"1341","type":"CID","arg1_id":"1324","arg2_id":"1328","normalized":[]},{"id":"1342","type":"CID","arg1_id":"1324","arg2_id":"1329","normalized":[]},{"id":"1343","type":"CID","arg1_id":"1324","arg2_id":"1330","normalized":[]},{"id":"1344","type":"CID","arg1_id":"1325","arg2_id":"1328","normalized":[]},{"id":"1345","type":"CID","arg1_id":"1325","arg2_id":"1329","normalized":[]},{"id":"1346","type":"CID","arg1_id":"1325","arg2_id":"1330","normalized":[]},{"id":"1347","type":"CID","arg1_id":"1331","arg2_id":"1328","normalized":[]},{"id":"1348","type":"CID","arg1_id":"1331","arg2_id":"1329","normalized":[]},{"id":"1349","type":"CID","arg1_id":"1331","arg2_id":"1330","normalized":[]}]}
{"id":"1350","document_id":"9848575","passages":[{"id":"1351","type":"title","text":["Chronic effects of a novel synthetic anthracycline derivative (SM-5887) on normal heart and doxorubicin-induced cardiomyopathy in beagle dogs."],"offsets":[[0,142]]},{"id":"1352","type":"abstract","text":["This study was designed to investigate the chronic cardiotoxic potential of SM-5887 and a possible deteriorating effect of SM-5887 on low-grade cardiotoxicity pre-induced by doxorubicin in beagle dogs. In the chronic treatment, beagle dogs of each sex were given intravenously once every 3 weeks, either a sublethal dose of doxorubicin (1.5 mg\/kg) or SM-5887 (2.5 mg\/kg). The experiment was terminated 3 weeks after the ninth dosing. Animals which received over six courses of doxorubicin demonstrated the electrocardiogram (ECG) changes, decrease of blood pressure and high-grade histopathological cardiomyopathy, while animals which were terminally sacrificed after the SM-5887 administration did not show any changes in ECG, blood pressure and histopathological examinations. To examine a possibly deteriorating cardiotoxic effect of SM-5887, low-grade cardiomyopathy was induced in dogs by four courses of doxorubicin (1.5 mg\/kg). Nine weeks after pre-treatment, dogs were given four courses of either doxorubicin (1.5 mg\/kg) or SM-5887 (2.5 mg\/kg) once every 3 weeks. The low-grade cardiotoxic changes were enhanced by the additional doxorubicin treatment. On the contrary, the SM-5887 treatment did not progress the grade of cardiomyopathy. In conclusion, SM-5887 does not have any potential of chronic cardiotoxicity and deteriorating effect on doxorubicin-induced cardiotoxicity in dogs."],"offsets":[[143,1538]]}],"entities":[{"id":"1353","type":"Chemical","text":["anthracycline"],"offsets":[[37,50]],"normalized":[{"db_name":"MESH","db_id":"D018943"}]},{"id":"1354","type":"Chemical","text":["SM-5887"],"offsets":[[63,70]],"normalized":[{"db_name":"MESH","db_id":"C055866"}]},{"id":"1355","type":"Chemical","text":["doxorubicin"],"offsets":[[92,103]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1356","type":"Disease","text":["cardiomyopathy"],"offsets":[[112,126]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"1357","type":"Disease","text":["cardiotoxic"],"offsets":[[194,205]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"1358","type":"Chemical","text":["SM-5887"],"offsets":[[219,226]],"normalized":[{"db_name":"MESH","db_id":"C055866"}]},{"id":"1359","type":"Chemical","text":["SM-5887"],"offsets":[[266,273]],"normalized":[{"db_name":"MESH","db_id":"C055866"}]},{"id":"1360","type":"Disease","text":["cardiotoxicity"],"offsets":[[287,301]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"1361","type":"Chemical","text":["doxorubicin"],"offsets":[[317,328]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1362","type":"Chemical","text":["doxorubicin"],"offsets":[[467,478]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1363","type":"Chemical","text":["SM-5887"],"offsets":[[494,501]],"normalized":[{"db_name":"MESH","db_id":"C055866"}]},{"id":"1364","type":"Chemical","text":["doxorubicin"],"offsets":[[620,631]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1365","type":"Disease","text":["cardiomyopathy"],"offsets":[[742,756]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"1366","type":"Chemical","text":["SM-5887"],"offsets":[[815,822]],"normalized":[{"db_name":"MESH","db_id":"C055866"}]},{"id":"1367","type":"Disease","text":["cardiotoxic"],"offsets":[[958,969]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"1368","type":"Chemical","text":["SM-5887"],"offsets":[[980,987]],"normalized":[{"db_name":"MESH","db_id":"C055866"}]},{"id":"1369","type":"Disease","text":["cardiomyopathy"],"offsets":[[999,1013]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"1370","type":"Chemical","text":["doxorubicin"],"offsets":[[1053,1064]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1371","type":"Chemical","text":["doxorubicin"],"offsets":[[1149,1160]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1372","type":"Chemical","text":["SM-5887"],"offsets":[[1176,1183]],"normalized":[{"db_name":"MESH","db_id":"C055866"}]},{"id":"1373","type":"Disease","text":["cardiotoxic"],"offsets":[[1230,1241]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"1374","type":"Chemical","text":["doxorubicin"],"offsets":[[1282,1293]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1375","type":"Chemical","text":["SM-5887"],"offsets":[[1326,1333]],"normalized":[{"db_name":"MESH","db_id":"C055866"}]},{"id":"1376","type":"Disease","text":["cardiomyopathy"],"offsets":[[1374,1388]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"1377","type":"Chemical","text":["SM-5887"],"offsets":[[1405,1412]],"normalized":[{"db_name":"MESH","db_id":"C055866"}]},{"id":"1378","type":"Disease","text":["cardiotoxicity"],"offsets":[[1452,1466]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"1379","type":"Chemical","text":["doxorubicin"],"offsets":[[1495,1506]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"1380","type":"Disease","text":["cardiotoxicity"],"offsets":[[1515,1529]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]}],"events":[],"coreferences":[],"relations":[{"id":"1381","type":"CID","arg1_id":"1355","arg2_id":"1356","normalized":[]},{"id":"1382","type":"CID","arg1_id":"1355","arg2_id":"1365","normalized":[]},{"id":"1383","type":"CID","arg1_id":"1355","arg2_id":"1369","normalized":[]},{"id":"1384","type":"CID","arg1_id":"1355","arg2_id":"1376","normalized":[]},{"id":"1385","type":"CID","arg1_id":"1361","arg2_id":"1356","normalized":[]},{"id":"1386","type":"CID","arg1_id":"1361","arg2_id":"1365","normalized":[]},{"id":"1387","type":"CID","arg1_id":"1361","arg2_id":"1369","normalized":[]},{"id":"1388","type":"CID","arg1_id":"1361","arg2_id":"1376","normalized":[]},{"id":"1389","type":"CID","arg1_id":"1362","arg2_id":"1356","normalized":[]},{"id":"1390","type":"CID","arg1_id":"1362","arg2_id":"1365","normalized":[]},{"id":"1391","type":"CID","arg1_id":"1362","arg2_id":"1369","normalized":[]},{"id":"1392","type":"CID","arg1_id":"1362","arg2_id":"1376","normalized":[]},{"id":"1393","type":"CID","arg1_id":"1364","arg2_id":"1356","normalized":[]},{"id":"1394","type":"CID","arg1_id":"1364","arg2_id":"1365","normalized":[]},{"id":"1395","type":"CID","arg1_id":"1364","arg2_id":"1369","normalized":[]},{"id":"1396","type":"CID","arg1_id":"1364","arg2_id":"1376","normalized":[]},{"id":"1397","type":"CID","arg1_id":"1370","arg2_id":"1356","normalized"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{"id":"1413","document_id":"9321531","passages":[{"id":"1414","type":"title","text":["Posteroventral medial pallidotomy in advanced Parkinson's disease."],"offsets":[[0,66]]},{"id":"1415","type":"abstract","text":["BACKGROUND: Posteroventral medial pallidotomy sometimes produces striking improvement in patients with advanced Parkinson's disease, but the studies to date have involved small numbers of patients and short-term follow-up. METHODS: Forty patients with Parkinson's disease underwent serial, detailed assessments both after drug withdrawal (\"off\" period) and while taking their optimal medical regimens (\"on\" period). All patients were examined preoperatively and 39 were examined at six months; 27 of the patients were also examined at one year, and 11 at two years. RESULTS: The percent improvements at six months were as follows: off-period score for overall motor function, 28 percent (95 percent confidence interval, 19 to 38 percent), with most of the improvement in the contralateral limbs; off-period score for activities of daily living, 29 percent (95 percent confidence interval, 19 to 39 percent); on-period score for contralateral dyskinesias, 82 percent (95 percent confidence interval, 72 to 91 percent); and on-period score for ipsilateral dyskinesias, 44 percent (95 percent confidence interval, 29 to 59 percent). The improvements in dyskinesias and the total scores for off-period parkinsonism, contralateral bradykinesia, and rigidity were sustained in the 11 patients examined at two years. The improvement in ipsilateral dyskinesias was lost after one year, and the improvements in postural stability and gait lasted only three to six months. Approximately half the patients who had been dependent on assistance in activities of daily living in the off period before surgery became independent after surgery. The complications of surgery were generally well tolerated, and there were no significant changes in the use of medication. CONCLUSIONS: In late-stage Parkinson's disease, pallidotomy significantly reduces levodopa-induced dyskinesias and off-period disability. Much of the benefit is sustained at two years, although some improvements, such as those on the ipsilateral side and in axial symptoms, wane within the first year. The on-period symptoms that are resistant to dopaminergic therapy do not respond to pallidotomy."],"offsets":[[67,2218]]}],"entities":[{"id":"1416","type":"Disease","text":["Parkinson's disease"],"offsets":[[46,65]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"1417","type":"Disease","text":["Parkinson's disease"],"offsets":[[179,198]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"1418","type":"Disease","text":["Parkinson's disease"],"offsets":[[319,338]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"1419","type":"Disease","text":["dyskinesias"],"offsets":[[1009,1020]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"1420","type":"Disease","text":["dyskinesias"],"offsets":[[1121,1132]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"1421","type":"Disease","text":["dyskinesias"],"offsets":[[1217,1228]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"1422","type":"Disease","text":["parkinsonism"],"offsets":[[1265,1277]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"1423","type":"Disease","text":["bradykinesia"],"offsets":[[1293,1305]],"normalized":[{"db_name":"MESH","db_id":"D018476"}]},{"id":"1424","type":"Disease","text":["rigidity"],"offsets":[[1311,1319]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"1425","type":"Disease","text":["dyskinesias"],"offsets":[[1408,1419]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"1426","type":"Disease","text":["Parkinson's disease"],"offsets":[[1847,1866]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"1427","type":"Chemical","text":["levodopa"],"offsets":[[1902,1910]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"1428","type":"Disease","text":["dyskinesias"],"offsets":[[1919,1930]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]}],"events":[],"coreferences":[],"relations":[{"id":"1429","type":"CID","arg1_id":"1427","arg2_id":"1419","normalized":[]},{"id":"1430","type":"CID","arg1_id":"1427","arg2_id":"1420","normalized":[]},{"id":"1431","type":"CID","arg1_id":"1427","arg2_id":"1421","normalized":[]},{"id":"1432","type":"CID","arg1_id":"1427","arg2_id":"1425","normalized":[]},{"id":"1433","type":"CID","arg1_id":"1427","arg2_id":"1428","normalized":[]}]}
{"id":"1434","document_id":"9305828","passages":[{"id":"1435","type":"title","text":["Neuropeptide-Y immunoreactivity in the pilocarpine model of temporal lobe epilepsy."],"offsets":[[0,83]]},{"id":"1436","type":"abstract","text":["Neuropeptide-Y (NPY) is expressed by granule cells and mossy fibres of the hippocampal dentate gyrus during experimental temporal lobe epilepsy (TLE). This expression may represent an endogenous damping mechanism since NPY has been shown to block seizure-like events following high-frequency stimulation in hippocampal slices. The pilocarpine (PILO) model of epilepsy is characterized by an acute period of status epilepticus followed by spontaneous recurrent seizures and related brain damage. We report peroxidase-antiperoxidase immunostaining for NPY in several brain regions in this model. PILO-injected animals exhibited NPY immunoreactivity in the region of the mossy fibre terminals, in the dentate gyrus inner molecular layer and, in a few cases, within presumed granule cells. NPY immunoreactivity was also dramatically changed in the entorhinal cortex, amygdala and sensorimotor areas. In addition, PILO injected animals exhibited a reduction in the number of NPY-immunoreactive interneurons compared with controls. The results demonstrate that changes in NPY expression, including expression in the granule cells and mossy fibres and the loss of vulnerable NPY neurons, are present in the PILO model of TLE. However, the significance of this changed synthesis of NPY remains to be determined."],"offsets":[[84,1387]]}],"entities":[{"id":"1437","type":"Chemical","text":["pilocarpine"],"offsets":[[39,50]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"1438","type":"Disease","text":["temporal lobe epilepsy"],"offsets":[[60,82]],"normalized":[{"db_name":"MESH","db_id":"D004833"}]},{"id":"1439","type":"Disease","text":["temporal lobe epilepsy"],"offsets":[[205,227]],"normalized":[{"db_name":"MESH","db_id":"D004833"}]},{"id":"1440","type":"Disease","text":["TLE"],"offsets":[[229,232]],"normalized":[{"db_name":"MESH","db_id":"D004833"}]},{"id":"1441","type":"Disease","text":["seizure"],"offsets":[[331,338]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"1442","type":"Chemical","text":["pilocarpine"],"offsets":[[415,426]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"1443","type":"Chemical","text":["PILO"],"offsets":[[428,432]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"1444","type":"Disease","text":["epilepsy"],"offsets":[[443,451]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"1445","type":"Disease","text":["status epilepticus"],"offsets":[[491,509]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"1446","type":"Disease","text":["seizures"],"offsets":[[544,552]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"1447","type":"Disease","text":["brain damage"],"offsets":[[565,577]],"normalized":[{"db_name":"MESH","db_id":"D001930"}]},{"id":"1448","type":"Chemical","text":["PILO"],"offsets":[[678,682]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"1449","type":"Chemical","text":["PILO"],"offsets":[[993,997]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"1450","type":"Chemical","text":["PILO"],"offsets":[[1284,1288]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"1451","type":"Disease","text":["TLE"],"offsets":[[1298,1301]],"normalized":[{"db_name":"MESH","db_id":"D004833"}]}],"events":[],"coreferences":[],"relations":[{"id":"1452","type":"CID","arg1_id":"1437","arg2_id":"1438","normalized":[]},{"id":"1453","type":"CID","arg1_id":"1437","arg2_id":"1439","normalized":[]},{"id":"1454","type":"CID","arg1_id":"1437","arg2_id":"1440","normalized":[]},{"id":"1455","type":"CID","arg1_id":"1437","arg2_id":"1451","normalized":[]},{"id":"1456","type":"CID","arg1_id":"1442","arg2_id":"1438","normalized":[]},{"id":"1457","type":"CID","arg1_id":"1442","arg2_id":"1439","normalized":[]},{"id":"1458","type":"CID","arg1_id":"1442","arg2_id":"1440","normalized":[]},{"id":"1459","type":"CID","arg1_id":"1442","arg2_id":"1451","normalized":[]},{"id":"1460","type":"CID","arg1_id":"1443","arg2_id":"1438","normalized":[]},{"id":"1461","type":"CID","arg1_id":"1443","arg2_id":"1439","normalized":[]},{"id":"1462","type":"CID","arg1_id":"1443","arg2_id":"1440","normalized":[]},{"id":"1463","type":"CID","arg1_id":"1443","arg2_id":"1451","normalized":[]},{"id":"1464","type":"CID","arg1_id":"1448","arg2_id":"1438","normalized":[]},{"id":"1465","type":"CID","arg1_id":"1448","arg2_id":"1439","normalized":[]},{"id":"1466","type":"CID","arg1_id":"1448","arg2_id":"1440","normalized":[]},{"id":"1467","type":"CID","arg1_id":"1448","arg2_id":"1451","normalized":[]},{"id":"1468","type":"CID","arg1_id":"1449","arg2_id":"1438","normalized":[]},{"id":"1469","type":"CID","arg1_id":"1449","arg2_id":"1439","normalized":[]},{"id":"1470","type":"CID","arg1_id":"1449","arg2_id":"1440","normalized":[]},{"id":"1471","type":"CID","arg1_id":"1449","arg2_id":"1451","normalized":[]},{"id":"1472","type":"CID","arg1_id":"1450","arg2_id":"1438","normalized":[]},{"id":"1473","type":"CID","arg1_id":"1450","arg2_id":"1439","normalized":[]},{"id":"1474","type":"CID","arg1_id":"1450","arg2_id":"1440","normalized":[]},{"id":"1475","type":"CID","arg1_id":"1450","arg2_id":"1451","normalized":[]}]}
{"id":"1476","document_id":"9041081","passages":[{"id":"1477","type":"title","text":["Effect of myopic excimer laser photorefractive keratectomy on the electrophysiologic function of the retina and optic nerve."],"offsets":[[0,124]]},{"id":"1478","type":"abstract","text":["PURPOSE: To assess by electrophysiologic testing the effect of photorefractive keratectomy (PRK) on the retina and optic nerve. SETTING: Eye Clinic, S. Salvatore Hospital, L'Aquila University, Italy. METHODS: Standard pattern electroretinograms (P-ERGs) and standard pattern visual evoked potentials (P-VEPs) were done in 25 eyes of 25 patients who had myopic PRK for an attempted correction between 5.00 and 15.00 diopters (D) (mean 8.00 D). Testing was done preoperatively and 3, 6, 12, and 18 months postoperatively. The contralateral eyes served as controls. During the follow-up, 3 patients (12%) developed steroid-induced elevated intraocular pressure (IOP) that resolved after corticosteroid therapy was discontinued. RESULTS: No statistically significant differences were seen between treated and control eyes nor between treated eyes preoperatively and postoperatively. CONCLUSION: Myopic excimer laser PRK did not seem to affect the posterior segment. The transient steroid-induced IOP rise did not seem to cause functional impairment."],"offsets":[[125,1170]]}],"entities":[{"id":"1479","type":"Chemical","text":["steroid"],"offsets":[[737,744]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"1480","type":"Disease","text":["elevated intraocular pressure"],"offsets":[[753,782]],"normalized":[{"db_name":"MESH","db_id":"D009798"}]},{"id":"1481","type":"Chemical","text":["corticosteroid"],"offsets":[[809,823]],"normalized":[{"db_name":"MESH","db_id":"D000305"}]},{"id":"1482","type":"Chemical","text":["steroid"],"offsets":[[1101,1108]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"1483","type":"Disease","text":["IOP rise"],"offsets":[[1117,1125]],"normalized":[{"db_name":"MESH","db_id":"D009798"}]}],"events":[],"coreferences":[],"relations":[{"id":"1484","type":"CID","arg1_id":"1481","arg2_id":"1480","normalized":[]},{"id":"1485","type":"CID","arg1_id":"1481","arg2_id":"1483","normalized":[]}]}
{"id":"1486","document_id":"8305357","passages":[{"id":"1487","type":"title","text":["Liposomal daunorubicin in advanced Kaposi's sarcoma: a phase II study."],"offsets":[[0,70]]},{"id":"1488","type":"abstract","text":["We report a non-randomized Phase II clinical trial to assess the efficacy and safety of liposomal daunorubicin (DaunoXome) in the treatment of AIDS related Kaposi's sarcoma. Eleven homosexual men with advanced Kaposi's sarcoma were entered in the trial. Changes in size, colour and associated oedema of selected 'target' lesions were measured. Clinical, biochemical and haematological toxicities were assessed. Ten subjects were evaluated. A partial response was achieved in four, of whom two subsequently relapsed. Stabilization of Kaposi's sarcoma occurred in the remaining six, maintained until the end of the trial period in four. The drug was generally well tolerated, with few mild symptoms of toxicity. The main problem encountered was haematological toxicity, with three subjects experiencing severe neutropenia (neutrophil count < 0.5 x 10(9)\/l). There was no evidence of cardiotoxicity. In this small patient sample, liposomal daunorubicin was an effective and well tolerated agent in the treatment of Kaposi's sarcoma."],"offsets":[[71,1100]]}],"entities":[{"id":"1489","type":"Chemical","text":["daunorubicin"],"offsets":[[10,22]],"normalized":[{"db_name":"MESH","db_id":"D003630"}]},{"id":"1490","type":"Disease","text":["Kaposi's sarcoma"],"offsets":[[35,51]],"normalized":[{"db_name":"MESH","db_id":"D012514"}]},{"id":"1491","type":"Chemical","text":["daunorubicin"],"offsets":[[169,181]],"normalized":[{"db_name":"MESH","db_id":"D003630"}]},{"id":"1492","type":"Disease","text":["AIDS"],"offsets":[[214,218]],"normalized":[{"db_name":"MESH","db_id":"D000163"}]},{"id":"1493","type":"Disease","text":["Kaposi's sarcoma"],"offsets":[[227,243]],"normalized":[{"db_name":"MESH","db_id":"D012514"}]},{"id":"1494","type":"Disease","text":["Kaposi's sarcoma"],"offsets":[[281,297]],"normalized":[{"db_name":"MESH","db_id":"D012514"}]},{"id":"1495","type":"Disease","text":["oedema"],"offsets":[[364,370]],"normalized":[{"db_name":"MESH","db_id":"D004487"}]},{"id":"1496","type":"Disease","text":["toxicities"],"offsets":[[456,466]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"1497","type":"Disease","text":["Kaposi's sarcoma"],"offsets":[[604,620]],"normalized":[{"db_name":"MESH","db_id":"D012514"}]},{"id":"1498","type":"Disease","text":["toxicity"],"offsets":[[771,779]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"1499","type":"Disease","text":["toxicity"],"offsets":[[829,837]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"1500","type":"Disease","text":["neutropenia"],"offsets":[[879,890]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"1501","type":"Disease","text":["cardiotoxicity"],"offsets":[[952,966]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"1502","type":"Chemical","text":["daunorubicin"],"offsets":[[1008,1020]],"normalized":[{"db_name":"MESH","db_id":"D003630"}]},{"id":"1503","type":"Disease","text":["Kaposi's sarcoma"],"offsets":[[1083,1099]],"normalized":[{"db_name":"MESH","db_id":"D012514"}]}],"events":[],"coreferences":[],"relations":[{"id":"1504","type":"CID","arg1_id":"1489","arg2_id":"1500","normalized":[]},{"id":"1505","type":"CID","arg1_id":"1491","arg2_id":"1500","normalized":[]},{"id":"1506","type":"CID","arg1_id":"1502","arg2_id":"1500","normalized":[]}]}
{"id":"1507","document_id":"8012887","passages":[{"id":"1508","type":"title","text":["Failure of ancrod in the treatment of heparin-induced arterial thrombosis."],"offsets":[[0,74]]},{"id":"1509","type":"abstract","text":["The morbidity and mortality associated with heparin-induced thrombosis remain high despite numerous empirical therapies. Ancrod has been used successfully for prophylaxis against development of thrombosis in patients with heparin induced platelet aggregation who require brief reexposure to heparin, but its success in patients who have developed the thrombosis syndrome is not well defined. The authors present a case of failure of ancrod treatment in a patient with heparin-induced thrombosis."],"offsets":[[75,570]]}],"entities":[{"id":"1510","type":"Chemical","text":["heparin"],"offsets":[[38,45]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"1511","type":"Disease","text":["thrombosis"],"offsets":[[63,73]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]},{"id":"1512","type":"Chemical","text":["heparin"],"offsets":[[119,126]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"1513","type":"Disease","text":["thrombosis"],"offsets":[[135,145]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]},{"id":"1514","type":"Disease","text":["thrombosis"],"offsets":[[269,279]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]},{"id":"1515","type":"Chemical","text":["heparin"],"offsets":[[297,304]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"1516","type":"Disease","text":["platelet aggregation"],"offsets":[[313,333]],"normalized":[{"db_name":"MESH","db_id":"D001791"}]},{"id":"1517","type":"Chemical","text":["heparin"],"offsets":[[366,373]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"1518","type":"Disease","text":["thrombosis"],"offsets":[[426,436]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]},{"id":"1519","type":"Chemical","text":["heparin"],"offsets":[[543,550]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"1520","type":"Disease","text":["thrombosis"],"offsets":[[559,569]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]}],"events":[],"coreferences":[],"relations":[{"id":"1521","type":"CID","arg1_id":"1510","arg2_id":"1511","normalized":[]},{"id":"1522","type":"CID","arg1_id":"1510","arg2_id":"1513","normalized":[]},{"id":"1523","type":"CID","arg1_id":"1510","arg2_id":"1514","normalized":[]},{"id":"1524","type":"CID","arg1_id":"1510","arg2_id":"1518","normalized":[]},{"id":"1525","type":"CID","arg1_id":"1510","arg2_id":"1520","normalized":[]},{"id":"1526","type":"CID","arg1_id":"1512","arg2_id":"1511","normalized":[]},{"id":"1527","type":"CID","arg1_id":"1512","arg2_id":"1513","normalized":[]},{"id":"1528","type":"CID","arg1_id":"1512","arg2_id":"1514","normalized":[]},{"id":"1529","type":"CID","arg1_id":"1512","arg2_id":"1518","normalized":[]},{"id":"1530","type":"CID","arg1_id":"1512","arg2_id":"1520","normalized":[]},{"id":"1531","type":"CID","arg1_id":"1515","arg2_id":"1511","normalized":[]},{"id":"1532","type":"CID","arg1_id":"1515","arg2_id":"1513","normalized":[]},{"id":"1533","type":"CID","arg1_id":"1515","arg2_id":"1514","normalized":[]},{"id":"1534","type":"CID","arg1_id":"1515","arg2_id":"1518","normalized":[]},{"id":"1535","type":"CID","arg1_id":"1515","arg2_id":"1520","normalized":[]},{"id":"1536","type":"CID","arg1_id":"1517","arg2_id":"1511","normalized":[]},{"id":"1537","type":"CID","arg1_id":"1517","arg2_id":"1513","normalized":[]},{"id":"1538","type":"CID","arg1_id":"1517","arg2_id":"1514","normalized":[]},{"id":"1539","type":"CID","arg1_id":"1517","arg2_id":"1518","normalized":[]},{"id":"1540","type":"CID","arg1_id":"1517","arg2_id":"1520","normalized":[]},{"id":"1541","type":"CID","arg1_id":"1519","arg2_id":"1511","normalized":[]},{"id":"1542","type":"CID","arg1_id":"1519","arg2_id":"1513","normalized":[]},{"id":"1543","type":"CID","arg1_id":"1519","arg2_id":"1514","normalized":[]},{"id":"1544","type":"CID","arg1_id":"1519","arg2_id":"1518","normalized":[]},{"id":"1545","type":"CID","arg1_id":"1519","arg2_id":"1520","normalized":[]}]}
{"id":"1546","document_id":"7651879","passages":[{"id":"1547","type":"title","text":["Seizure after flumazenil administration in a pediatric patient."],"offsets":[[0,63]]},{"id":"1548","type":"abstract","text":["Flumazenil is a benzodiazepine receptor antagonist used to reverse sedation and respiratory depression induced by benzodiazepines. Seizures and cardiac arrhythmias have complicated its use in adult patients. Overdose patients who have coingested tricyclic antidepressants have a higher risk of these complications. Little information exists concerning adverse effects of flumazenil in children. We report the occurrence of a generalized tonic-clonic seizure in a pediatric patient following the administration of flumazenil."],"offsets":[[64,588]]}],"entities":[{"id":"1549","type":"Disease","text":["Seizure"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"1550","type":"Chemical","text":["flumazenil"],"offsets":[[14,24]],"normalized":[{"db_name":"MESH","db_id":"D005442"}]},{"id":"1551","type":"Chemical","text":["Flumazenil"],"offsets":[[64,74]],"normalized":[{"db_name":"MESH","db_id":"D005442"}]},{"id":"1552","type":"Chemical","text":["benzodiazepine"],"offsets":[[80,94]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]},{"id":"1553","type":"Disease","text":["respiratory depression"],"offsets":[[144,166]],"normalized":[{"db_name":"MESH","db_id":"D012131"}]},{"id":"1554","type":"Chemical","text":["benzodiazepines"],"offsets":[[178,193]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]},{"id":"1555","type":"Disease","text":["Seizures"],"offsets":[[195,203]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"1556","type":"Disease","text":["cardiac arrhythmias"],"offsets":[[208,227]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"1557","type":"Disease","text":["Overdose"],"offsets":[[272,280]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"1558","type":"Chemical","text":["flumazenil"],"offsets":[[435,445]],"normalized":[{"db_name":"MESH","db_id":"D005442"}]},{"id":"1559","type":"Disease","text":["tonic-clonic seizure"],"offsets":[[501,521]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"1560","type":"Chemical","text":["flumazenil"],"offsets":[[577,587]],"normalized":[{"db_name":"MESH","db_id":"D005442"}]}],"events":[],"coreferences":[],"relations":[{"id":"1561","type":"CID","arg1_id":"1550","arg2_id":"1549","normalized":[]},{"id":"1562","type":"CID","arg1_id":"1550","arg2_id":"1555","normalized":[]},{"id":"1563","type":"CID","arg1_id":"1550","arg2_id":"1559","normalized":[]},{"id":"1564","type":"CID","arg1_id":"1551","arg2_id":"1549","normalized":[]},{"id":"1565","type":"CID","arg1_id":"1551","arg2_id":"1555","normalized":[]},{"id":"1566","type":"CID","arg1_id":"1551","arg2_id":"1559","normalized":[]},{"id":"1567","type":"CID","arg1_id":"1558","arg2_id":"1549","normalized":[]},{"id":"1568","type":"CID","arg1_id":"1558","arg2_id":"1555","normalized":[]},{"id":"1569","type":"CID","arg1_id":"1558","arg2_id":"1559","normalized":[]},{"id":"1570","type":"CID","arg1_id":"1560","arg2_id":"1549","normalized":[]},{"id":"1571","type":"CID","arg1_id":"1560","arg2_id":"1555","normalized":[]},{"id":"1572","type":"CID","arg1_id":"1560","arg2_id":"1559","normalized":[]}]}
{"id":"1573","document_id":"3015327","passages":[{"id":"1574","type":"title","text":["Remodelling of nerve structure in experimental isoniazid neuropathy in the rat."],"offsets":[[0,79]]},{"id":"1575","type":"abstract","text":["The neuropathy caused by a single dose of isoniazid in rats was studied with a computer-assisted morphometric method. Scatter diagrams of the g ratio (quotient fibre diameter\/axon diameter) define regenerating fibres as a distinct population, distinguishable from the surviving fibres by reduced sheath thickness and reduced axon calibre. There was also evidence of a subtle direct toxic effect on the entire fibre population, causing axon shrinkage masked by readjustment of the myelin sheath."],"offsets":[[80,574]]}],"entities":[{"id":"1576","type":"Chemical","text":["isoniazid"],"offsets":[[47,56]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]},{"id":"1577","type":"Disease","text":["neuropathy"],"offsets":[[57,67]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"1578","type":"Disease","text":["neuropathy"],"offsets":[[84,94]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"1579","type":"Chemical","text":["isoniazid"],"offsets":[[122,131]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]}],"events":[],"coreferences":[],"relations":[{"id":"1580","type":"CID","arg1_id":"1576","arg2_id":"1577","normalized":[]},{"id":"1581","type":"CID","arg1_id":"1576","arg2_id":"1578","normalized":[]},{"id":"1582","type":"CID","arg1_id":"1579","arg2_id":"1577","normalized":[]},{"id":"1583","type":"CID","arg1_id":"1579","arg2_id":"1578","normalized":[]}]}
{"id":"1584","document_id":"2980315","passages":[{"id":"1585","type":"title","text":["Selective injection of iopentol, iohexol and metrizoate into the left coronary artery of the dog. Induction of ventricular fibrillation and decrease of aortic pressure."],"offsets":[[0,168]]},{"id":"1586","type":"abstract","text":["In twenty beagle dogs selective injections were made into the left coronary artery with iopentol, iohexol and metrizoate in doses of 4 ml, 8 ml and 16 ml. Thirty-six iopentol injections, 35 iohexol injections and 37 metrizoate injections were made. Frequencies of ventricular fibrillation were significantly lower (p less than 0.05) after iopentol (0%) and iohexol (3%) than after metrizoate (22%). Iopentol and iohexol also produced significantly less decrease in aortic blood pressure than metrizoate at the different doses."],"offsets":[[169,695]]}],"entities":[{"id":"1587","type":"Chemical","text":["iopentol"],"offsets":[[23,31]],"normalized":[{"db_name":"MESH","db_id":"C053571"}]},{"id":"1588","type":"Chemical","text":["iohexol"],"offsets":[[33,40]],"normalized":[{"db_name":"MESH","db_id":"D007472"}]},{"id":"1589","type":"Chemical","text":["metrizoate"],"offsets":[[45,55]],"normalized":[{"db_name":"MESH","db_id":"D008794"}]},{"id":"1590","type":"Disease","text":["ventricular fibrillation"],"offsets":[[111,135]],"normalized":[{"db_name":"MESH","db_id":"D014693"}]},{"id":"1591","type":"Chemical","text":["iopentol"],"offsets":[[257,265]],"normalized":[{"db_name":"MESH","db_id":"C053571"}]},{"id":"1592","type":"Chemical","text":["iohexol"],"offsets":[[267,274]],"normalized":[{"db_name":"MESH","db_id":"D007472"}]},{"id":"1593","type":"Chemical","text":["metrizoate"],"offsets":[[279,289]],"normalized":[{"db_name":"MESH","db_id":"D008794"}]},{"id":"1594","type":"Chemical","text":["iopentol"],"offsets":[[335,343]],"normalized":[{"db_name":"MESH","db_id":"C053571"}]},{"id":"1595","type":"Chemical","text":["iohexol"],"offsets":[[359,366]],"normalized":[{"db_name":"MESH","db_id":"D007472"}]},{"id":"1596","type":"Chemical","text":["metrizoate"],"offsets":[[385,395]],"normalized":[{"db_name":"MESH","db_id":"D008794"}]},{"id":"1597","type":"Disease","text":["ventricular fibrillation"],"offsets":[[433,457]],"normalized":[{"db_name":"MESH","db_id":"D014693"}]},{"id":"1598","type":"Chemical","text":["iopentol"],"offsets":[[508,516]],"normalized":[{"db_name":"MESH","db_id":"C053571"}]},{"id":"1599","type":"Chemical","text":["iohexol"],"offsets":[[526,533]],"normalized":[{"db_name":"MESH","db_id":"D007472"}]},{"id":"1600","type":"Chemical","text":["metrizoate"],"offsets":[[550,560]],"normalized":[{"db_name":"MESH","db_id":"D008794"}]},{"id":"1601","type":"Chemical","text":["Iopentol"],"offsets":[[568,576]],"normalized":[{"db_name":"MESH","db_id":"C053571"}]},{"id":"1602","type":"Chemical","text":["iohexol"],"offsets":[[581,588]],"normalized":[{"db_name":"MESH","db_id":"D007472"}]},{"id":"1603","type":"Chemical","text":["metrizoate"],"offsets":[[661,671]],"normalized":[{"db_name":"MESH","db_id":"D008794"}]}],"events":[],"coreferences":[],"relations":[{"id":"1604","type":"CID","arg1_id":"1589","arg2_id":"1590","normalized":[]},{"id":"1605","type":"CID","arg1_id":"1589","arg2_id":"1597","normalized":[]},{"id":"1606","type":"CID","arg1_id":"1593","arg2_id":"1590","normalized":[]},{"id":"1607","type":"CID","arg1_id":"1593","arg2_id":"1597","normalized":[]},{"id":"1608","type":"CID","arg1_id":"1596","arg2_id":"1590","normalized":[]},{"id":"1609","type":"CID","arg1_id":"1596","arg2_id":"1597","normalized":[]},{"id":"1610","type":"CID","arg1_id":"1600","arg2_id":"1590","normalized":[]},{"id":"1611","type":"CID","arg1_id":"1600","arg2_id":"1597","normalized":[]},{"id":"1612","type":"CID","arg1_id":"1603","arg2_id":"1590","normalized":[]},{"id":"1613","type":"CID","arg1_id":"1603","arg2_id":"1597","normalized":[]}]}
{"id":"1614","document_id":"2819587","passages":[{"id":"1615","type":"title","text":["Magnetic resonance imaging of cerebral venous thrombosis secondary to \"low-dose\" birth control pills."],"offsets":[[0,101]]},{"id":"1616","type":"abstract","text":["The clinical and radiographic features of cerebral deep venous thrombosis in a 21-year-old white woman are presented. This nulliparous patient presented with relatively mild clinical symptoms and progressing mental status changes. The only known risk factor was \"low-dose\" oral contraceptive pills. The magnetic resonance image (MRI) showed increased signal intensity from the internal cerebral veins, vein of Galen, and straight sinus. The diagnosis was confirmed by arterial angiography."],"offsets":[[102,591]]}],"entities":[{"id":"1617","type":"Disease","text":["venous thrombosis"],"offsets":[[39,56]],"normalized":[{"db_name":"MESH","db_id":"D020246"}]},{"id":"1618","type":"Disease","text":["deep venous thrombosis"],"offsets":[[153,175]],"normalized":[{"db_name":"MESH","db_id":"D020246"}]},{"id":"1619","type":"Chemical","text":["oral contraceptive"],"offsets":[[375,393]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]}],"events":[],"coreferences":[],"relations":[{"id":"1620","type":"CID","arg1_id":"1619","arg2_id":"1617","normalized":[]},{"id":"1621","type":"CID","arg1_id":"1619","arg2_id":"1618","normalized":[]}]}
{"id":"1622","document_id":"1564236","passages":[{"id":"1623","type":"title","text":["Relation of perfusion defects observed with myocardial contrast echocardiography to the severity of coronary stenosis: correlation with thallium-201 single-photon emission tomography."],"offsets":[[0,183]]},{"id":"1624","type":"abstract","text":["It has been previously shown that myocardial contrast echocardiography is a valuable technique for delineating regions of myocardial underperfusion secondary to coronary occlusion and to critical coronary stenoses in the presence of hyperemic stimulation. The aim of this study was to determine whether myocardial contrast echocardiography performed with a stable solution of sonicated albumin could detect regions of myocardial underperfusion resulting from various degrees of coronary stenosis. The perfusion defect produced in 16 open chest dogs was compared with the anatomic area at risk measured by the postmortem dual-perfusion technique and with thallium-201 single-photon emission tomography (SPECT). During a transient (20-s) coronary occlusion, a perfusion defect was observed with contrast echocardiography in 14 of the 15 dogs in which the occlusion was produced. The perfusion defect correlated significantly with the anatomic area at risk (r = 0.74; p less than 0.002). During dipyridamole-induced hyperemia, 12 of the 16 dogs with a partial coronary stenosis had a visible area of hypoperfusion by contrast echocardiography. The four dogs without a perfusion defect had a stenosis that resulted in a mild (0% to 50%) reduction in dipyridamole-induced hyperemia. The size of the perfusion defect during stenosis correlated significantly with the anatomic area at risk (r = 0.61; p = 0.02). Thallium-201 SPECT demonstrated a perfusion defect in all 14 dogs analyzed during dipyridamole-induced hyperemia; the size of the perfusion defect correlated with the anatomic area at risk (r = 0.58; p less than 0.03) and with the perfusion defect by contrast echocardiography (r = 0.58; p less than 0.03). Thus, myocardial contrast echocardiography can be used to visualize and quantitate the amount of jeopardized myocardium during moderate to severe degrees of coronary stenosis. The results obtained show a correlation with the anatomic area at risk similar to that obtained with thallium-201 SPECT."],"offsets":[[184,2192]]}],"entities":[{"id":"1625","type":"Disease","text":["coronary stenosis"],"offsets":[[100,117]],"normalized":[{"db_name":"MESH","db_id":"D023921"}]},{"id":"1626","type":"Chemical","text":["thallium"],"offsets":[[136,144]],"normalized":[{"db_name":"MESH","db_id":"D013793"}]},{"id":"1627","type":"Disease","text":["coronary occlusion"],"offsets":[[345,363]],"normalized":[{"db_name":"MESH","db_id":"D054059"}]},{"id":"1628","type":"Disease","text":["coronary stenoses"],"offsets":[[380,397]],"normalized":[{"db_name":"MESH","db_id":"D023921"}]},{"id":"1629","type":"Disease","text":["hyperemic"],"offsets":[[417,426]],"normalized":[{"db_name":"MESH","db_id":"D006940"}]},{"id":"1630","type":"Disease","text":["coronary stenosis"],"offsets":[[662,679]],"normalized":[{"db_name":"MESH","db_id":"D023921"}]},{"id":"1631","type":"Chemical","text":["thallium"],"offsets":[[838,846]],"normalized":[{"db_name":"MESH","db_id":"D013793"}]},{"id":"1632","type":"Disease","text":["coronary occlusion"],"offsets":[[920,938]],"normalized":[{"db_name":"MESH","db_id":"D054059"}]},{"id":"1633","type":"Chemical","text":["dipyridamole"],"offsets":[[1176,1188]],"normalized":[{"db_name":"MESH","db_id":"D004176"}]},{"id":"1634","type":"Disease","text":["hyperemia"],"offsets":[[1197,1206]],"normalized":[{"db_name":"MESH","db_id":"D006940"}]},{"id":"1635","type":"Disease","text":["coronary stenosis"],"offsets":[[1241,1258]],"normalized":[{"db_name":"MESH","db_id":"D023921"}]},{"id":"1636","type":"Chemical","text":["dipyridamole"],"offsets":[[1430,1442]],"normalized":[{"db_name":"MESH","db_id":"D004176"}]},{"id":"1637","type":"Disease","text":["hyperemia"],"offsets":[[1451,1460]],"normalized":[{"db_name":"MESH","db_id":"D006940"}]},{"id":"1638","type":"Chemical","text":["Thallium"],"offsets":[[1589,1597]],"normalized":[{"db_name":"MESH","db_id":"D013793"}]},{"id":"1639","type":"Chemical","text":["dipyridamole"],"offsets":[[1671,1683]],"normalized":[{"db_name":"MESH","db_id":"D004176"}]},{"id":"1640","type":"Disease","text":["hyperemia"],"offsets":[[1692,1701]],"normalized":[{"db_name":"MESH","db_id":"D006940"}]},{"id":"1641","type":"Disease","text":["coronary stenosis"],"offsets":[[2053,2070]],"normalized":[{"db_name":"MESH","db_id":"D023921"}]},{"id":"1642","type":"Chemical","text":["thallium"],"offsets":[[2173,2181]],"normalized":[{"db_name":"MESH","db_id":"D013793"}]}],"events":[],"coreferences":[],"relations":[{"id":"1643","type":"CID","arg1_id":"1633","arg2_id":"1629","normalized":[]},{"id":"1644","type":"CID","arg1_id":"1633","arg2_id":"1634","normalized":[]},{"id":"1645","type":"CID","arg1_id":"1633","arg2_id":"1637","normalized":[]},{"id":"1646","type":"CID","arg1_id":"1633","arg2_id":"1640","normalized":[]},{"id":"1647","type":"CID","arg1_id":"1636","arg2_id":"1629","normalized":[]},{"id":"1648","type":"CID","arg1_id":"1636","arg2_id":"1634","normalized":[]},{"id":"1649","type":"CID","arg1_id":"1636","arg2_id":"1637","normalized":[]},{"id":"1650","type":"CID","arg1_id":"1636","arg2_id":"1640","normalized":[]},{"id":"1651","type":"CID","arg1_id":"1639","arg2_id":"1629","normalized":[]},{"id":"1652","type":"CID","arg1_id":"1639","arg2_id":"1634","normalized":[]},{"id":"1653","type":"CID","arg1_id":"1639","arg2_id":"1637","normalized":[]},{"id":"1654","type":"CID","arg1_id":"1639","arg2_id":"1640","normalized":[]}]}
{"id":"1655","document_id":"1300436","passages":[{"id":"1656","type":"title","text":["Potential deleterious effect of furosemide in radiocontrast nephropathy."],"offsets":[[0,72]]},{"id":"1657","type":"abstract","text":["The purpose of the study was to determine the efficacy of furosemide in addition to intravenous fluids in the prevention of radiocontrast nephropathy. 18 patients, referred to a radiocontrast study, considered at risk because of preexisting renal insufficiency, were enrolled in a prospective, randomized, controlled trial, performed at the secondary care center of a 1,100-bed private university hospital. In addition to fluids, the treatment group received furosemide (mean dose 110 mg) intravenously 30 min prior to the injection of contrast material. The control group received fluids (mean 3 liters). Radiological studies were mostly angiographies performed with both ionic and non-ionic contrast material, at an average dose of 245 ml. Renal function significantly deteriorated in the group pretreated with furosemide (p < 0.005 by ANOVA), with a rise in serum creatinine from 145 +\/- 13 to 182 +\/- 16 mumol\/l at 24 h, while no change occurred in the control group (from 141 +\/- 6 to 142 +\/- 7 mumol\/l). Renal failure was associated with weight loss in the furosemide-treated group. Furosemide may be deleterious in the prevention of radiocontrast nephropathy."],"offsets":[[73,1239]]}],"entities":[{"id":"1658","type":"Chemical","text":["furosemide"],"offsets":[[32,42]],"normalized":[{"db_name":"MESH","db_id":"D005665"}]},{"id":"1659","type":"Disease","text":["nephropathy"],"offsets":[[60,71]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"1660","type":"Chemical","text":["furosemide"],"offsets":[[131,141]],"normalized":[{"db_name":"MESH","db_id":"D005665"}]},{"id":"1661","type":"Disease","text":["nephropathy"],"offsets":[[211,222]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"1662","type":"Disease","text":["renal insufficiency"],"offsets":[[314,333]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"1663","type":"Chemical","text":["furosemide"],"offsets":[[532,542]],"normalized":[{"db_name":"MESH","db_id":"D005665"}]},{"id":"1664","type":"Disease","text":["Renal function significantly deteriorated"],"offsets":[[815,856]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"1665","type":"Chemical","text":["furosemide"],"offsets":[[886,896]],"normalized":[{"db_name":"MESH","db_id":"D005665"}]},{"id":"1666","type":"Chemical","text":["creatinine"],"offsets":[[940,950]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"1667","type":"Disease","text":["Renal failure"],"offsets":[[1083,1096]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"1668","type":"Disease","text":["weight loss"],"offsets":[[1117,1128]],"normalized":[{"db_name":"MESH","db_id":"D015431"}]},{"id":"1669","type":"Chemical","text":["furosemide"],"offsets":[[1136,1146]],"normalized":[{"db_name":"MESH","db_id":"D005665"}]},{"id":"1670","type":"Chemical","text":["Furosemide"],"offsets":[[1162,1172]],"normalized":[{"db_name":"MESH","db_id":"D005665"}]},{"id":"1671","type":"Disease","text":["nephropathy"],"offsets":[[1227,1238]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"1672","type":"CID","arg1_id":"1658","arg2_id":"1664","normalized":[]},{"id":"1673","type":"CID","arg1_id":"1660","arg2_id":"1664","normalized":[]},{"id":"1674","type":"CID","arg1_id":"1663","arg2_id":"1664","normalized":[]},{"id":"1675","type":"CID","arg1_id":"1665","arg2_id":"1664","normalized":[]},{"id":"1676","type":"CID","arg1_id":"1669","arg2_id":"1664","normalized":[]},{"id":"1677","type":"CID","arg1_id":"1670","arg2_id":"1664","normalized":[]}]}
{"id":"1678","document_id":"1141447","passages":[{"id":"1679","type":"title","text":["The renal pathology in a case of lithium-induced diabetes insipidus."],"offsets":[[0,68]]},{"id":"1680","type":"abstract","text":["A case of lithium-induced diabetes insipidus is reported. At necropsy microscopy shoed unique and extensive damage to cells lining the distal nephron. It is suggested that these changes represent a specific toxic effect of lithium, reported here for the first time in man."],"offsets":[[69,341]]}],"entities":[{"id":"1681","type":"Chemical","text":["lithium"],"offsets":[[33,40]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"1682","type":"Disease","text":["diabetes insipidus"],"offsets":[[49,67]],"normalized":[{"db_name":"MESH","db_id":"D003919"}]},{"id":"1683","type":"Chemical","text":["lithium"],"offsets":[[79,86]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"1684","type":"Disease","text":["diabetes insipidus"],"offsets":[[95,113]],"normalized":[{"db_name":"MESH","db_id":"D003919"}]},{"id":"1685","type":"Chemical","text":["lithium"],"offsets":[[292,299]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]}],"events":[],"coreferences":[],"relations":[{"id":"1686","type":"CID","arg1_id":"1681","arg2_id":"1682","normalized":[]},{"id":"1687","type":"CID","arg1_id":"1681","arg2_id":"1684","normalized":[]},{"id":"1688","type":"CID","arg1_id":"1683","arg2_id":"1682","normalized":[]},{"id":"1689","type":"CID","arg1_id":"1683","arg2_id":"1684","normalized":[]},{"id":"1690","type":"CID","arg1_id":"1685","arg2_id":"1682","normalized":[]},{"id":"1691","type":"CID","arg1_id":"1685","arg2_id":"1684","normalized":[]}]}
{"id":"1692","document_id":"188339","passages":[{"id":"1693","type":"title","text":["Etiologic factors in the pathogenesis of liver tumors associated with oral contraceptives."],"offsets":[[0,90]]},{"id":"1694","type":"abstract","text":["Within the last several years, previously rare liver tumors have been seen in young women using oral contraceptive steroids. The Registry for Liver Tumors Associated with Oral Contraceptives at the University of California, Irvine, has clearly identified 27 cases. The recent literature contains 44 case reports. Common to these 71 cases has been a histopathologic diagnosis of focal nodular hyperplasia, adenoma, hamartoma, and hepatoma. Significant statistical etiologic factors include prolonged uninterrupted usage of oral contraceptive steroids. Eight deaths and liver rupture in 18 patients attest to the seriousness of this new potentially lethal adverse phenomenon."],"offsets":[[91,764]]}],"entities":[{"id":"1695","type":"Disease","text":["liver tumors"],"offsets":[[41,53]],"normalized":[{"db_name":"MESH","db_id":"D008113"}]},{"id":"1696","type":"Chemical","text":["oral contraceptives"],"offsets":[[70,89]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"1697","type":"Disease","text":["liver tumors"],"offsets":[[138,150]],"normalized":[{"db_name":"MESH","db_id":"D008113"}]},{"id":"1698","type":"Chemical","text":["oral contraceptive"],"offsets":[[187,205]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"1699","type":"Chemical","text":["steroids"],"offsets":[[206,214]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"1700","type":"Disease","text":["Liver Tumors"],"offsets":[[233,245]],"normalized":[{"db_name":"MESH","db_id":"D008113"}]},{"id":"1701","type":"Chemical","text":["Oral Contraceptives"],"offsets":[[262,281]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"1702","type":"Disease","text":["focal nodular hyperplasia"],"offsets":[[469,494]],"normalized":[{"db_name":"MESH","db_id":"D020518"}]},{"id":"1703","type":"Disease","text":["adenoma"],"offsets":[[496,503]],"normalized":[{"db_name":"MESH","db_id":"D000236"}]},{"id":"1704","type":"Disease","text":["hamartoma"],"offsets":[[505,514]],"normalized":[{"db_name":"MESH","db_id":"D006222"}]},{"id":"1705","type":"Disease","text":["hepatoma"],"offsets":[[520,528]],"normalized":[{"db_name":"MESH","db_id":"D006528"}]},{"id":"1706","type":"Chemical","text":["oral contraceptive"],"offsets":[[613,631]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"1707","type":"Chemical","text":["steroids"],"offsets":[[632,640]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"1708","type":"Disease","text":["rupture"],"offsets":[[665,672]],"normalized":[{"db_name":"MESH","db_id":"D012421"}]}],"events":[],"coreferences":[],"relations":[{"id":"1709","type":"CID","arg1_id":"1696","arg2_id":"1695","normalized":[]},{"id":"1710","type":"CID","arg1_id":"1696","arg2_id":"1697","normalized":[]},{"id":"1711","type":"CID","arg1_id":"1696","arg2_id":"1700","normalized":[]},{"id":"1712","type":"CID","arg1_id":"1698","arg2_id":"1695","normalized":[]},{"id":"1713","type":"CID","arg1_id":"1698","arg2_id":"1697","normalized":[]},{"id":"1714","type":"CID","arg1_id":"1698","arg2_id":"1700","normalized":[]},{"id":"1715","type":"CID","arg1_id":"1701","arg2_id":"1695","normalized":[]},{"id":"1716","type":"CID","arg1_id":"1701","arg2_id":"1697","normalized":[]},{"id":"1717","type":"CID","arg1_id":"1701","arg2_id":"1700","normalized":[]},{"id":"1718","type":"CID","arg1_id":"1706","arg2_id":"1695","normalized":[]},{"id":"1719","type":"CID","arg1_id":"1706","arg2_id":"1697","normalized":[]},{"id":"1720","type":"CID","arg1_id":"1706","arg2_id":"1700","normalized":[]}]}
{"id":"1721","document_id":"19135948","passages":[{"id":"1722","type":"title","text":["Graft-versus-host disease prophylaxis with everolimus and tacrolimus is associated with a high incidence of sinusoidal obstruction syndrome and microangiopathy: results of the EVTAC trial."],"offsets":[[0,188]]},{"id":"1723","type":"abstract","text":["A calcineurin inhibitor combined with methotrexate is the standard prophylaxis for graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Everolimus, a derivative of sirolimus, seems to mediate antileukemia effects. We report on a combination of everolimus and tacrolimus in 24 patients (median age, 62 years) with either myelodysplastic syndrome (MDS; n = 17) or acute myeloid leukemia (AML; n = 7) undergoing intensive conditioning followed by HSCT from related (n = 4) or unrelated (n = 20) donors. All patients engrafted, and only 1 patient experienced grade IV mucositis. Nine patients (37%) developed acute grade II-IV GVHD, and 11 of 17 evaluable patients (64%) developed chronic extensive GVHD. Transplantation-associated microangiopathy (TMA) occurred in 7 patients (29%), with 2 cases of acute renal failure. The study was terminated prematurely because an additional 6 patients (25%) developed sinusoidal obstruction syndrome (SOS), which was fatal in 2 cases. With a median follow-up of 26 months, the 2-year overall survival rate was 47%. Although this new combination appears to be effective as a prophylactic regimen for acute GVHD, the incidence of TMA and SOS is considerably higher than seen with other regimens."],"offsets":[[189,1462]]}],"entities":[{"id":"1724","type":"Disease","text":["Graft-versus-host disease"],"offsets":[[0,25]],"normalized":[{"db_name":"MESH","db_id":"D006086"}]},{"id":"1725","type":"Chemical","text":["everolimus"],"offsets":[[43,53]],"normalized":[{"db_name":"MESH","db_id":"C107135"}]},{"id":"1726","type":"Chemical","text":["tacrolimus"],"offsets":[[58,68]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"1727","type":"Disease","text":["sinusoidal obstruction syndrome"],"offsets":[[108,139]],"normalized":[{"db_name":"MESH","db_id":"D006504"}]},{"id":"1728","type":"Disease","text":["microangiopathy"],"offsets":[[144,159]],"normalized":[{"db_name":"MESH","db_id":"D014652"}]},{"id":"1729","type":"Chemical","text":["methotrexate"],"offsets":[[227,239]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"1730","type":"Disease","text":["graft-versus-host disease"],"offsets":[[272,297]],"normalized":[{"db_name":"MESH","db_id":"D006086"}]},{"id":"1731","type":"Disease","text":["GVHD"],"offsets":[[299,303]],"normalized":[{"db_name":"MESH","db_id":"D006086"}]},{"id":"1732","type":"Chemical","text":["Everolimus"],"offsets":[[370,380]],"normalized":[{"db_name":"MESH","db_id":"C107135"}]},{"id":"1733","type":"Chemical","text":["sirolimus"],"offsets":[[398,407]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"1734","type":"Chemical","text":["everolimus"],"offsets":[[478,488]],"normalized":[{"db_name":"MESH","db_id":"C107135"}]},{"id":"1735","type":"Chemical","text":["tacrolimus"],"offsets":[[493,503]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"1736","type":"Disease","text":["myelodysplastic syndrome"],"offsets":[[554,578]],"normalized":[{"db_name":"MESH","db_id":"D009190"}]},{"id":"1737","type":"Disease","text":["MDS"],"offsets":[[580,583]],"normalized":[{"db_name":"MESH","db_id":"D009190"}]},{"id":"1738","type":"Disease","text":["acute myeloid leukemia"],"offsets":[[596,618]],"normalized":[{"db_name":"MESH","db_id":"D015470"}]},{"id":"1739","type":"Disease","text":["AML"],"offsets":[[620,623]],"normalized":[{"db_name":"MESH","db_id":"D015470"}]},{"id":"1740","type":"Disease","text":["mucositis"],"offsets":[[798,807]],"normalized":[{"db_name":"MESH","db_id":"D052016"}]},{"id":"1741","type":"Disease","text":["GVHD"],"offsets":[[857,861]],"normalized":[{"db_name":"MESH","db_id":"D006086"}]},{"id":"1742","type":"Disease","text":["GVHD"],"offsets":[[929,933]],"normalized":[{"db_name":"MESH","db_id":"D006086"}]},{"id":"1743","type":"Disease","text":["Transplantation-associated microangiopathy"],"offsets":[[935,977]],"normalized":[{"db_name":"MESH","db_id":"D014652"}]},{"id":"1744","type":"Disease","text":["TMA"],"offsets":[[979,982]],"normalized":[{"db_name":"MESH","db_id":"D014652"}]},{"id":"1745","type":"Disease","text":["acute renal failure"],"offsets":[[1030,1049]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"1746","type":"Disease","text":["sinusoidal obstruction 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{"id":"1796","document_id":"14704468","passages":[{"id":"1797","type":"title","text":["Effect of some convulsants on the protective activity of loreclezole and its combinations with valproate or clonazepam in amygdala-kindled rats."],"offsets":[[0,144]]},{"id":"1798","type":"abstract","text":["Loreclezole (5 mg\/kg) exerted a significant protective action in amygdala-kindled rats, reducing both seizure and afterdischarge durations. The combinations of loreclezole (2.5 mg\/kg) with valproate, clonazepam, or carbamazepine (applied at their subprotective doses) also exhibited antiseizure effect in this test. However, only two first combinations occurred to be of pharmacodynamic nature. Among several chemoconvulsants, bicuculline, N-methyl-D-aspartic acid and BAY k-8644 (the opener of L-type calcium channels) reversed the protective activity of loreclezole alone and its combination with valproate. On the other hand, bicuculline, aminophylline and BAY k-8644 inhibited the anticonvulsive action of loreclezole combined with clonazepam. The results support the hypothesis that the protective activity of loreclezole and its combinations with other antiepileptics may involve potentiation of GABAergic neurotransmission and blockade of L-type of calcium channels."],"offsets":[[145,1118]]}],"entities":[{"id":"1799","type":"Chemical","text":["loreclezole"],"offsets":[[57,68]],"normalized":[{"db_name":"MESH","db_id":"C066440"}]},{"id":"1800","type":"Chemical","text":["valproate"],"offsets":[[95,104]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"1801","type":"Chemical","text":["clonazepam"],"offsets":[[108,118]],"normalized":[{"db_name":"MESH","db_id":"D002998"}]},{"id":"1802","type":"Chemical","text":["Loreclezole"],"offsets":[[145,156]],"normalized":[{"db_name":"MESH","db_id":"C066440"}]},{"id":"1803","type":"Disease","text":["seizure"],"offsets":[[247,254]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"1804","type":"Chemical","text":["loreclezole"],"offsets":[[305,316]],"normalized":[{"db_name":"MESH","db_id":"C066440"}]},{"id":"1805","type":"Chemical","text":["valproate"],"offsets":[[334,343]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"1806","type":"Chemical","text":["clonazepam"],"offsets":[[345,355]],"normalized":[{"db_name":"MESH","db_id":"D002998"}]},{"id":"1807","type":"Chemical","text":["carbamazepine"],"offsets":[[360,373]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"1808","type":"Chemical","text":["bicuculline"],"offsets":[[572,583]],"normalized":[{"db_name":"MESH","db_id":"D001640"}]},{"id":"1809","type":"Chemical","text":["N-methyl-D-aspartic acid"],"offsets":[[585,609]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"1810","type":"Chemical","text":["BAY k-8644"],"offsets":[[614,624]],"normalized":[{"db_name":"MESH","db_id":"D001498"}]},{"id":"1811","type":"Chemical","text":["calcium"],"offsets":[[647,654]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"1812","type":"Chemical","text":["loreclezole"],"offsets":[[701,712]],"normalized":[{"db_name":"MESH","db_id":"C066440"}]},{"id":"1813","type":"Chemical","text":["valproate"],"offsets":[[744,753]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"1814","type":"Chemical","text":["bicuculline"],"offsets":[[774,785]],"normalized":[{"db_name":"MESH","db_id":"D001640"}]},{"id":"1815","type":"Chemical","text":["aminophylline"],"offsets":[[787,800]],"normalized":[{"db_name":"MESH","db_id":"D000628"}]},{"id":"1816","type":"Chemical","text":["BAY k-8644"],"offsets":[[805,815]],"normalized":[{"db_name":"MESH","db_id":"D001498"}]},{"id":"1817","type":"Chemical","text":["loreclezole"],"offsets":[[855,866]],"normalized":[{"db_name":"MESH","db_id":"C066440"}]},{"id":"1818","type":"Chemical","text":["clonazepam"],"offsets":[[881,891]],"normalized":[{"db_name":"MESH","db_id":"D002998"}]},{"id":"1819","type":"Chemical","text":["loreclezole"],"offsets":[[960,971]],"normalized":[{"db_name":"MESH","db_id":"C066440"}]},{"id":"1820","type":"Chemical","text":["calcium"],"offsets":[[1101,1108]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]}],"events":[],"coreferences":[],"relations":[{"id":"1821","type":"CID","arg1_id":"1808","arg2_id":"1803","normalized":[]},{"id":"1822","type":"CID","arg1_id":"1814","arg2_id":"1803","normalized":[]},{"id":"1823","type":"CID","arg1_id":"1815","arg2_id":"1803","normalized":[]},{"id":"1824","type":"CID","arg1_id":"1810","arg2_id":"1803","normalized":[]},{"id":"1825","type":"CID","arg1_id":"1816","arg2_id":"1803","normalized":[]}]}
{"id":"1826","document_id":"12549952","passages":[{"id":"1827","type":"title","text":["Acute liver failure with concurrent bupropion and carbimazole therapy."],"offsets":[[0,70]]},{"id":"1828","type":"abstract","text":["OBJECTIVE: To report a case of fatal liver failure possibly associated with concurrent use of bupropion and carbimazole. CASE SUMMARY: A 41-year-old Chinese man with a history of hyperthyroidism had been treated with carbimazole and propranolol for the past 5 years. He received a 10-day course of bupropion as an aid for smoking cessation 10 weeks prior to presentation. He developed acute liver failure with rapid deterioration of renal function. Liver biopsy showed evidence of nonspecific drug-induced acute liver injury. His condition was further complicated by sepsis and coagulopathy. Death resulted 19 days after the onset of symptoms. The likelihood that bupropion induced hepatotoxicity in our patient was possible, based on the Naranjo probability scale. DISCUSSION: Although there is increasing evidence of hepatotoxicity induced by bupropion, this is the first case of fatality that could have resulted from acute liver failure in a patient receiving bupropion while on concomitant treatment with carbimazole. CONCLUSIONS: Clinicians should be aware of the possibility of acute liver insult induced by bupropion given concurrently with other hepatotoxic drugs."],"offsets":[[71,1244]]}],"entities":[{"id":"1829","type":"Disease","text":["Acute liver failure"],"offsets":[[0,19]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"1830","type":"Chemical","text":["bupropion"],"offsets":[[36,45]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"1831","type":"Chemical","text":["carbimazole"],"offsets":[[50,61]],"normalized":[{"db_name":"MESH","db_id":"D002231"}]},{"id":"1832","type":"Disease","text":["liver 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{"id":"1941","document_id":"19370593","passages":[{"id":"1942","type":"title","text":["Long term hormone therapy for perimenopausal and postmenopausal women."],"offsets":[[0,70]]},{"id":"1943","type":"abstract","text":["BACKGROUND: Hormone therapy (HT) is widely used for controlling menopausal symptoms and has also been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women. This is an updated version of the original Cochrane review first published in 2005. OBJECTIVES: To assess the effect of long-term HT on mortality, cardiovascular outcomes, cancer, gallbladder disease, cognition, fractures and quality of life. SEARCH STRATEGY: We searched the following databases to November 2007: Trials Register of the Cochrane Menstrual Disorders and Subfertility Group, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Biological Abstracts. Also relevant non-indexed journals and conference abstracts. SELECTION CRITERIA: Randomised double-blind trials of HT versus placebo, taken for at least one year by perimenopausal or postmenopausal women. HT included oestrogens, with or without progestogens, via oral, transdermal, subcutaneous or transnasal routes. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. MAIN RESULTS: Nineteen trials involving 41,904 women were included. In relatively healthy women, combined continuous HT significantly increased the risk of venous thrombo-embolism or coronary event (after one year's use), stroke (after three years), breast cancer and gallbladder disease. Long-term oestrogen-only HT significantly increased the risk of venous thrombo-embolism, stroke and gallbladder disease (after one to two years, three years and seven years' use respectively), but did not significantly increase the risk of breast cancer. The only statistically significant benefits of HT were a decreased incidence of fractures and (for combined HT) colon cancer, with long-term use. Among women aged over 65 who were relatively healthy (i.e. generally fit, without overt disease) and taking continuous combined HT, there was a statistically significant increase in the incidence of dementia. Among women with cardiovascular disease, long-term use of combined continuous HT significantly increased the risk of venous thrombo-embolism.One trial analysed subgroups of 2839 relatively healthy 50 to 59 year old women taking combined continuous HT and 1637 taking oestrogen-only HT, versus similar-sized placebo groups. The only significantly increased risk reported was for venous thrombo-embolism in women taking combined continuous HT: their absolute risk remained low, at less than 1\/500. However, this study was not powered to detect differences between groups of younger women. AUTHORS' CONCLUSIONS: HT is not indicated for the routine management of chronic disease. We need more evidence on the safety of HT for menopausal symptom control, though short-term use appears to be relatively safe for healthy younger women."],"offsets":[[71,2901]]}],"entities":[{"id":"1944","type":"Disease","text":["cardiovascular disease"],"offsets":[[215,237]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"1945","type":"Disease","text":["osteoporosis"],"offsets":[[239,251]],"normalized":[{"db_name":"MESH","db_id":"D010024"}]},{"id":"1946","type":"Disease","text":["dementia"],"offsets":[[256,264]],"normalized":[{"db_name":"MESH","db_id":"D003704"}]},{"id":"1947","type":"Disease","text":["cancer"],"offsets":[[453,459]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"1948","type":"Disease","text":["gallbladder disease"],"offsets":[[461,480]],"normalized":[{"db_name":"MESH","db_id":"D005705"}]},{"id":"1949","type":"Disease","text":["fractures"],"offsets":[[493,502]],"normalized":[{"db_name":"MESH","db_id":"D050723"}]},{"id":"1950","type":"Disease","text":["Menstrual Disorders"],"offsets":[[627,646]],"normalized":[{"db_name":"MESH","db_id":"D008599"}]},{"id":"1951","type":"Chemical","text":["oestrogens"],"offsets":[[975,985]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"1952","type":"Chemical","text":["progestogens"],"offsets":[[1003,1015]],"normalized":[{"db_name":"MESH","db_id":"D011374"}]},{"id":"1953","type":"Disease","text":["venous thrombo-embolism"],"offsets":[[1330,1353]],"normalized":[{"db_name":"MESH","db_id":"D054556"}]},{"id":"1954","type":"Disease","text":["stroke"],"offsets":[[1396,1402]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"1955","type":"Disease","text":["breast cancer"],"offsets":[[1424,1437]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"1956","type":"Disease","text":["gallbladder disease"],"offsets":[[1442,1461]],"normalized":[{"db_name":"MESH","db_id":"D005705"}]},{"id":"1957","type":"Chemical","text":["oestrogen"],"offsets":[[1473,1482]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"1958","type":"Disease","text":["venous thrombo-embolism"],"offsets":[[1527,1550]],"normalized":[{"db_name":"MESH","db_id":"D054556"}]},{"id":"1959","type":"Disease","text":["stroke"],"offsets":[[1552,1558]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"1960","type":"Disease","text":["gallbladder disease"],"offsets":[[1563,1582]],"normalized":[{"db_name":"MESH","db_id":"D005705"}]},{"id":"1961","type":"Disease","text":["breast cancer"],"offsets":[[1703,1716]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"1962","type":"Disease","text":["fractures"],"offsets":[[1798,1807]],"normalized":[{"db_name":"MESH","db_id":"D050723"}]},{"id":"1963","type":"Disease","text":["colon cancer"],"offsets":[[1830,1842]],"normalized":[{"db_name":"MESH","db_id":"D003110"}]},{"id":"1964","type":"Disease","text":["dementia"],"offsets":[[2063,2071]],"normalized":[{"db_name":"MESH","db_id":"D003704"}]},{"id":"1965","type":"Disease","text":["cardiovascular disease"],"offsets":[[2090,2112]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"1966","type":"Disease","text":["venous thrombo-embolism"],"offsets":[[2190,2213]],"normalized":[{"db_name":"MESH","db_id":"D054556"}]},{"id":"1967","type":"Chemical","text":["oestrogen"],"offsets":[[2340,2349]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"1968","type":"Disease","text":["venous thrombo-embolism"],"offsets":[[2451,2474]],"normalized":[{"db_name":"MESH","db_id":"D054556"}]}],"events":[],"coreferences":[],"relations":[{"id":"1969","type":"CID","arg1_id":"1952","arg2_id":"1953","normalized":[]},{"id":"1970","type":"CID","arg1_id":"1952","arg2_id":"1958","normalized":[]},{"id":"1971","type":"CID","arg1_id":"1952","arg2_id":"1966","normalized":[]},{"id":"1972","type":"CID","arg1_id":"1952","arg2_id":"1968","normalized":[]},{"id":"1973","type":"CID","arg1_id":"1951","arg2_id":"1948","normalized":[]},{"id":"1974","type":"CID","arg1_id":"1951","arg2_id":"1956","normalized":[]},{"id":"1975","type":"CID","arg1_id":"1951","arg2_id":"1960","normalized":[]},{"id":"1976","type":"CID","arg1_id":"1957","arg2_id":"1948","normalized":[]},{"id":"1977","type":"CID","arg1_id":"1957","arg2_id":"1956","normalized":[]},{"id":"1978","type":"CID","arg1_id":"1957","arg2_id":"1960","normalized":[]},{"id":"1979","type":"CID","arg1_id":"1967","arg2_id":"1948","normalized":[]},{"id":"1980","type":"CID","arg1_id":"1967","arg2_id":"1956","normalized":[]},{"id":"1981","type":"CID","arg1_id":"1967","arg2_id":"1960","normalized":[]},{"id":"1982","type":"CID","arg1_id":"1951","arg2_id":"1954","normalized":[]},{"id":"1983","type":"CID","arg1_id":"1951","arg2_id":"1959","normalized":[]},{"id":"1984","type":"CID","arg1_id":"1957","arg2_id":"1954","normalized":[]},{"id":"1985","type":"CID","arg1_id":"1957","arg2_id":"1959","normalized":[]},{"id":"1986","type":"CID","arg1_id":"1967","arg2_id":"1954","normalized":[]},{"id":"1987","type":"CID","arg1_id":"1967","arg2_id":"1959","normalized":[]},{"id":"1988","type":"CID","arg1_id":"1951","arg2_id":"1953","normalized":[]},{"id":"1989","type":"CID","arg1_id":"1951","arg2_id":"1958","normalized":[]},{"id":"1990","type":"CID","arg1_id":"1951","arg2_id":"1966","normalized":[]},{"id":"1991","type":"CID","arg1_id":"1951","arg2_id":"1968","normalized":[]},{"id":"1992","type":"CID","arg1_id":"1957","arg2_id":"1953","normalized":[]},{"id":"1993","type":"CID","arg1_id":"1957","arg2_id":"1958","normalized":[]},{"id":"1994","type":"CID","arg1_id":"1957","arg2_id":"1966","normalized":[]},{"id":"1995","type":"CID","arg1_id":"1957","arg2_id":"1968","normalized":[]},{"id":"1996","type":"CID","arg1_id":"1967","arg2_id":"1953","normalized":[]},{"id":"1997","type":"CID","arg1_id":"1967","arg2_id":"1958","normalized":[]},{"id":"1998","type":"CID","arg1_id":"1967","arg2_id":"1966","normalized":[]},{"id":"1999","type":"CID","arg1_id":"1967","arg2_id":"1968","normalized":[]},{"id":"2000","type":"CID","arg1_id":"1951","arg2_id":"1946","normalized":[]},{"id":"2001","type":"CID","arg1_id":"1951","arg2_id":"1964","normalized":[]},{"id":"2002","type":"CID","arg1_id":"1957","arg2_id":"1946","normalized":[]},{"id":"2003","type":"CID","arg1_id":"1957","arg2_id":"1964","normalized":[]},{"id":"2004","type":"CID","arg1_id":"1967","arg2_id":"1946","normalized":[]},{"id":"2005","type":"CID","arg1_id":"1967","arg2_id":"1964","normalized":[]},{"id":"2006","type":"CID","arg1_id":"1952","arg2_id":"1946","normalized":[]},{"id":"2007","type":"CID","arg1_id":"1952","arg2_id":"1964","normalized":[]}]}
{"id":"2008","document_id":"17019386","passages":[{"id":"2009","type":"title","text":["Passage of mannitol into the brain around gliomas: a potential cause of rebound phenomenon. A study on 21 patients."],"offsets":[[0,115]]},{"id":"2010","type":"abstract","text":["AIM: Widespread use of mannitol to reduce brain edema and lower elevated ICP in brain tumor patients continues to be afflicted by the so-called rebound phenomenon. Leakage of mannitol into the brain parenchyma through an altered BBB and secondary reversal of osmotic gradient is considered the major cause of rebound . This has only been demonstrated experimentally in animals. As a contribution to this issue we decided to research the possible passage of mannitol into the brain after administration to 21 brain tumor patients. METHODS: Mannitol (18% solution; 1 g\/kg) was administered as a bolus to patients (ten had malignant glioma, seven brain metastases and four meningioma) about 30 minutes before craniotomy. During resection, a sample of the surrounding edematous white matter was taken at the same time as a 10 ml venous blood sample. Mannitol concentrations were measured in plasma and white matter by a modified version of the enzyme assay of Blonquist et al. RESULTS: In most glioma patients, mannitol concentrations in white matter were 2 to 6 times higher than in plasma (mean 3.5 times). In meningioma and metastases patients plasma concentrations of mannitol were higher than white matter concentrations except in three cases with infiltration by neoplastic cells. CONCLUSIONS: The results of our study show that even after a single bolus, mannitol may leak through the altered BBB near gliomas, reversing the initial plasma-to-blood osmotic gradient, aggravating peritumoral edema and promoting rebound of ICP."],"offsets":[[116,1645]]}],"entities":[{"id":"2011","type":"Chemical","text":["mannitol"],"offsets":[[11,19]],"normalized":[{"db_name":"MESH","db_id":"D008353"}]},{"id":"2012","type":"Disease","text":["gliomas"],"offsets":[[42,49]],"normalized":[{"db_name":"MESH","db_id":"D005910"}]},{"id":"2013","type":"Chemical","text":["mannitol"],"offsets":[[139,147]],"normalized":[{"db_name":"MESH","db_id":"D008353"}]},{"id":"2014","type":"Disease","text":["brain edema"],"offsets":[[158,169]],"normalized":[{"db_name":"MESH","db_id":"D001929"}]},{"id":"2015","type":"Disease","text":["elevated ICP"],"offsets":[[180,192]],"normalized":[{"db_name":"MESH","db_id":"D019586"}]},{"id":"2016","type":"Disease","text":["brain tumor"],"offsets":[[196,207]],"normalized":[{"db_name":"MESH","db_id":"D001932"}]},{"id":"2017","type":"Chemical","text":["mannitol"],"offsets":[[291,299]],"normalized":[{"db_name":"MESH","db_id":"D008353"}]},{"id":"2018","type":"Chemical","text":["mannitol"],"offsets":[[573,581]],"normalized":[{"db_name":"MESH","db_id":"D008353"}]},{"id":"2019","type":"Disease","text":["brain tumor"],"offsets":[[624,635]],"normalized":[{"db_name":"MESH","db_id":"D001932"}]},{"id":"2020","type":"Chemical","text":["Mannitol"],"offsets":[[655,663]],"normalized":[{"db_name":"MESH","db_id":"D008353"}]},{"id":"2021","type":"Disease","text":["malignant glioma"],"offsets":[[736,752]],"normalized":[{"db_name":"MESH","db_id":"D005910"}]},{"id":"2022","type":"Disease","text":["metastases"],"offsets":[[766,776]],"normalized":[{"db_name":"MESH","db_id":"D009362"}]},{"id":"2023","type":"Disease","text":["meningioma"],"offsets":[[786,796]],"normalized":[{"db_name":"MESH","db_id":"D008579"}]},{"id":"2024","type":"Disease","text":["edematous"],"offsets":[[880,889]],"normalized":[{"db_name":"MESH","db_id":"D004487"}]},{"id":"2025","type":"Chemical","text":["Mannitol"],"offsets":[[962,970]],"normalized":[{"db_name":"MESH","db_id":"D008353"}]},{"id":"2026","type":"Disease","text":["glioma"],"offsets":[[1106,1112]],"normalized":[{"db_name":"MESH","db_id":"D005910"}]},{"id":"2027","type":"Chemical","text":["mannitol"],"offsets":[[1123,1131]],"normalized":[{"db_name":"MESH","db_id":"D008353"}]},{"id":"2028","type":"Disease","text":["meningioma"],"offsets":[[1224,1234]],"normalized":[{"db_name":"MESH","db_id":"D008579"}]},{"id":"2029","type":"Disease","text":["metastases"],"offsets":[[1239,1249]],"normalized":[{"db_name":"MESH","db_id":"D009362"}]},{"id":"2030","type":"Chemical","text":["mannitol"],"offsets":[[1284,1292]],"normalized":[{"db_name":"MESH","db_id":"D008353"}]},{"id":"2031","type":"Chemical","text":["mannitol"],"offsets":[[1474,1482]],"normalized":[{"db_name":"MESH","db_id":"D008353"}]},{"id":"2032","type":"Disease","text":["gliomas"],"offsets":[[1521,1528]],"normalized":[{"db_name":"MESH","db_id":"D005910"}]},{"id":"2033","type":"Disease","text":["edema"],"offsets":[[1610,1615]],"normalized":[{"db_name":"MESH","db_id":"D004487"}]}],"events":[],"coreferences":[],"relations":[{"id":"2034","type":"CID","arg1_id":"2011","arg2_id":"2015","normalized":[]},{"id":"2035","type":"CID","arg1_id":"2013","arg2_id":"2015","normalized":[]},{"id":"2036","type":"CID","arg1_id":"2017","arg2_id":"2015","normalized":[]},{"id":"2037","type":"CID","arg1_id":"2018","arg2_id":"2015","normalized":[]},{"id":"2038","type":"CID","arg1_id":"2020","arg2_id":"2015","normalized":[]},{"id":"2039","type":"CID","arg1_id":"2025","arg2_id":"2015","normalized":[]},{"id":"2040","type":"CID","arg1_id":"2027","arg2_id":"2015","normalized":[]},{"id":"2041","type":"CID","arg1_id":"2030","arg2_id":"2015","normalized":[]},{"id":"2042","type":"CID","arg1_id":"2031","arg2_id":"2015","normalized":[]}]}
{"id":"2043","document_id":"12452237","passages":[{"id":"2044","type":"title","text":["Can lidocaine reduce succinylcholine induced postoperative myalgia?"],"offsets":[[0,67]]},{"id":"2045","type":"abstract","text":["This study was undertaken to determine the effect of lidocaine pretreatment on reduction of succinylcholine-induced myalgia in patients undergoing general anesthesia for gynecological surgery. One hundred and thirty-five patients were assigned to one of three groups in a prospective, double blind, randomized manner. Group PS, the control group, received normal saline and succinylcholine 1.5 mg x kg(-1); Group LS, lidocaine 1.5 mg x kg(-1) and succinylcholine 1.5 mg x kg(-1); Group PR, normal saline and rocuronium 0.6 mg x kg(-1). Morphine 0.1 mg x kg(-1) iv was given for premedication and all patients were monitored with a noninvasive blood pressure monitor, ECG and pulse oximetry. Anesthesia was induced with 5 mg.kg(-1) thiopental iv. followed by succinylcholine (Group PS, LS) or rocuronium (Group PR) for tracheal intubation. Following administration of these agents, the presence, and degree of fasciculation were assessed visually on a four point scale by one investigator who was blinded to the drug administered. The blood pressure and heart rate of each patient were monitored on nine occasions. Twenty-four hours later, any myalgia experienced was assessed according to a structured questionaire and graded by a four point scale by one investigator blinded to the intraoperative management. The results indicate that muscle fasciculation was not found in Group PR while the patients in Group LS had a lower incidence of muscle fasciculation than those in Group PS (p < 0.001). At 24 h, the incidence of myalgia was higher in Group PS than in Group LS and PR (p < 0.05). A correlation was not found between the incidence of myalgia and the occurrence of muscle fasciculation. The changes in systolic and diastolic blood pressure and heart rate were not significant among the three groups. In conclusion, where succinylcholine is used, lidocaine is proven to be the useful pretreatment agent for the reduction of postoperative myalgia."],"offsets":[[68,2020]]}],"entities":[{"id":"2046","type":"Chemical","text":["lidocaine"],"offsets":[[4,13]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"2047","type":"Chemical","text":["succinylcholine"],"offsets":[[21,36]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"2048","type":"Disease","text":["postoperative myalgia"],"offsets":[[45,66]],"normalized":[{"db_name":"MESH","db_id":"D010149"}]},{"id":"2049","type":"Chemical","text":["lidocaine"],"offsets":[[121,130]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"2050","type":"Chemical","text":["succinylcholine"],"offsets":[[160,175]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"2051","type":"Disease","text":["myalgia"],"offsets":[[184,191]],"normalized":[{"db_name":"MESH","db_id":"D063806"}]},{"id":"2052","type":"Chemical","text":["succinylcholine"],"offsets":[[442,457]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"2053","type":"Chemical","text":["lidocaine"],"offsets":[[485,494]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"2054","type":"Chemical","text":["succinylcholine"],"offsets":[[515,530]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"2055","type":"Chemical","text":["rocuronium"],"offsets":[[576,586]],"normalized":[{"db_name":"MESH","db_id":"C061870"}]},{"id":"2056","type":"Chemical","text":["Morphine"],"offsets":[[604,612]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"2057","type":"Chemical","text":["thiopental"],"offsets":[[799,809]],"normalized":[{"db_name":"MESH","db_id":"D013874"}]},{"id":"2058","type":"Chemical","text":["succinylcholine"],"offsets":[[826,841]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"2059","type":"Chemical","text":["rocuronium"],"offsets":[[860,870]],"normalized":[{"db_name":"MESH","db_id":"C061870"}]},{"id":"2060","type":"Disease","text":["fasciculation"],"offsets":[[977,990]],"normalized":[{"db_name":"MESH","db_id":"D005207"}]},{"id":"2061","type":"Disease","text":["myalgia"],"offsets":[[1211,1218]],"normalized":[{"db_name":"MESH","db_id":"D063806"}]},{"id":"2062","type":"Disease","text":["muscle fasciculation"],"offsets":[[1404,1424]],"normalized":[{"db_name":"MESH","db_id":"D005207"}]},{"id":"2063","type":"Disease","text":["muscle fasciculation"],"offsets":[[1507,1527]],"normalized":[{"db_name":"MESH","db_id":"D005207"}]},{"id":"2064","type":"Disease","text":["myalgia"],"offsets":[[1590,1597]],"normalized":[{"db_name":"MESH","db_id":"D063806"}]},{"id":"2065","type":"Disease","text":["myalgia"],"offsets":[[1710,1717]],"normalized":[{"db_name":"MESH","db_id":"D063806"}]},{"id":"2066","type":"Disease","text":["muscle fasciculation"],"offsets":[[1740,1760]],"normalized":[{"db_name":"MESH","db_id":"D005207"}]},{"id":"2067","type":"Chemical","text":["succinylcholine"],"offsets":[[1896,1911]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"2068","type":"Chemical","text":["lidocaine"],"offsets":[[1921,1930]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"2069","type":"Disease","text":["postoperative myalgia"],"offsets":[[1998,2019]],"normalized":[{"db_name":"MESH","db_id":"D010149"}]}],"events":[],"coreferences":[],"relations":[{"id":"2070","type":"CID","arg1_id":"2047","arg2_id":"2060","normalized":[]},{"id":"2071","type":"CID","arg1_id":"2047","arg2_id":"2062","normalized":[]},{"id":"2072","type":"CID","arg1_id":"2047","arg2_id":"2063","normalized":[]},{"id":"2073","type":"CID","arg1_id":"2047","arg2_id":"2066","normalized":[]},{"id":"2074","type":"CID","arg1_id":"2050","arg2_id":"2060","normalized":[]},{"id":"2075","type":"CID","arg1_id":"2050","arg2_id":"2062","normalized":[]},{"id":"2076","type":"CID","arg1_id":"2050","arg2_id":"2063","normalized":[]},{"id":"2077","type":"CID","arg1_id":"2050","arg2_id":"2066","normalized":[]},{"id":"2078","type":"CID","arg1_id":"2052","arg2_id":"2060","normalized":[]},{"id":"2079","type":"CID","arg1_id":"2052","arg2_id":"2062","normalized":[]},{"id":"2080","type":"CID","arg1_id":"2052","arg2_id":"2063","normalized":[]},{"id":"2081","type":"CID","arg1_id":"2052","arg2_id":"2066","normalized":[]},{"id":"2082","type":"CID","arg1_id":"2054","arg2_id":"2060","normalized":[]},{"id":"2083","type":"CID","arg1_id":"2054","arg2_id":"2062","normalized":[]},{"id":"2084","type":"CID","arg1_id":"2054","arg2_id":"2063","normalized":[]},{"id":"2085","type":"CID","arg1_id":"2054","arg2_id":"2066","normalized":[]},{"id":"2086","type":"CID","arg1_id":"2058","arg2_id":"2060","normalized":[]},{"id":"2087","type":"CID","arg1_id":"2058","arg2_id":"2062","normalized":[]},{"id":"2088","type":"CID","arg1_id":"2058","arg2_id":"2063","normalized":[]},{"id":"2089","type":"CID","arg1_id":"2058","arg2_id":"2066","normalized":[]},{"id":"2090","type":"CID","arg1_id":"2067","arg2_id":"2060","normalized":[]},{"id":"2091","type":"CID","arg1_id":"2067","arg2_id":"2062","normalized":[]},{"id":"2092","type":"CID","arg1_id":"2067","arg2_id":"2063","normalized":[]},{"id":"2093","type":"CID","arg1_id":"2067","arg2_id":"2066","normalized":[]},{"id":"2094","type":"CID","arg1_id":"2047","arg2_id":"2048","normalized":[]},{"id":"2095","type":"CID","arg1_id":"2047","arg2_id":"2069","normalized":[]},{"id":"2096","type":"CID","arg1_id":"2050","arg2_id":"2048","normalized":[]},{"id":"2097","type":"CID","arg1_id":"2050","arg2_id":"2069","normalized":[]},{"id":"2098","type":"CID","arg1_id":"2052","arg2_id":"2048","normalized":[]},{"id":"2099","type":"CID","arg1_id":"2052","arg2_id":"2069","normalized":[]},{"id":"2100","type":"CID","arg1_id":"2054","arg2_id":"2048","normalized":[]},{"id":"2101","type":"CID","arg1_id":"2054","arg2_id":"2069","normalized":[]},{"id":"2102","type":"CID","arg1_id":"2058","arg2_id":"2048","normalized":[]},{"id":"2103","type":"CID","arg1_id":"2058","arg2_id":"2069","normalized":[]},{"id":"2104","type":"CID","arg1_id":"2067","arg2_id":"2048","normalized":[]},{"id":"2105","type":"CID","arg1_id":"2067","arg2_id":"2069","normalized":[]}]}
{"id":"2106","document_id":"9564988","passages":[{"id":"2107","type":"title","text":["Open-label assessment of levofloxacin for the treatment of acute bacterial sinusitis in adults."],"offsets":[[0,95]]},{"id":"2108","type":"abstract","text":["PURPOSE: To evaluate the efficacy and safety of levofloxacin (500 mg orally once daily for 10 to 14 days) in treating adult outpatients with acute bacterial sinusitis. PATIENTS AND METHODS: A total of 329 patients enrolled in the study at 24 centers. All patients had a pre-therapy Gram's stain and culture of sinus exudate obtained by antral puncture or nasal endoscopy. Clinical response was assessed on the basis of signs and symptoms and sinus radiograph or computed tomography results. Microbiologic cure rates were determined on the basis of presumed plus documented eradication of the pre-therapy pathogen(s). RESULTS: The most common pathogens were Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, and Moraxella catarrhalis. Of 300 clinically evaluable patients, 175 (58%) were cured and 90 (30%) were improved at the post-therapy evaluation, resulting in a clinical success rate of 88%. Thirty-five patients (12%) clinically failed treatment. The microbiologic eradication rate (presumed plus documented) among 138 microbiologically evaluable patients was 92%. Microbiologic eradication rates (presumed plus documented) of the most common pathogens ranged from 93% (M. catarrhalis) to 100% (S. pneumoniae) at the post-therapy visit. All but one of the 265 patients who were cured or improved at post-therapy returned for a long-term follow-up visit; 243 (92%) remained well 4 to 6 weeks after therapy; and 21 (8%) had a relapse of symptoms. Adverse events considered to be related to levofloxacin administration were reported by 29 patients (9%). The most common drug-related adverse events were diarrhea, flatulence, and nausea; most adverse events were mild to moderate in severity. CONCLUSION: The results of this study indicate that levofloxacin 500 mg once daily is an effective and safe treatment for acute bacterial sinusitis."],"offsets":[[96,1962]]}],"entities":[{"id":"2109","type":"Chemical","text":["levofloxacin"],"offsets":[[25,37]],"normalized":[{"db_name":"MESH","db_id":"D064704"}]},{"id":"2110","type":"Disease","text":["sinusitis"],"offsets":[[75,84]],"normalized":[{"db_name":"MESH","db_id":"D012852"}]},{"id":"2111","type":"Chemical","text":["levofloxacin"],"offsets":[[144,156]],"normalized":[{"db_name":"MESH","db_id":"D064704"}]},{"id":"2112","type":"Disease","text":["sinusitis"],"offsets":[[253,262]],"normalized":[{"db_name":"MESH","db_id":"D012852"}]},{"id":"2113","type":"Chemical","text":["levofloxacin"],"offsets":[[1613,1625]],"normalized":[{"db_name":"MESH","db_id":"D064704"}]},{"id":"2114","type":"Disease","text":["diarrhea"],"offsets":[[1725,1733]],"normalized":[{"db_name":"MESH","db_id":"D003967"}]},{"id":"2115","type":"Disease","text":["flatulence"],"offsets":[[1735,1745]],"normalized":[{"db_name":"MESH","db_id":"D005414"}]},{"id":"2116","type":"Disease","text":["nausea"],"offsets":[[1751,1757]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"2117","type":"Chemical","text":["levofloxacin"],"offsets":[[1866,1878]],"normalized":[{"db_name":"MESH","db_id":"D064704"}]},{"id":"2118","type":"Disease","text":["sinusitis"],"offsets":[[1952,1961]],"normalized":[{"db_name":"MESH","db_id":"D012852"}]}],"events":[],"coreferences":[],"relations":[{"id":"2119","type":"CID","arg1_id":"2109","arg2_id":"2115","normalized":[]},{"id":"2120","type":"CID","arg1_id":"2111","arg2_id":"2115","normalized":[]},{"id":"2121","type":"CID","arg1_id":"2113","arg2_id":"2115","normalized":[]},{"id":"2122","type":"CID","arg1_id":"2117","arg2_id":"2115","normalized":[]},{"id":"2123","type":"CID","arg1_id":"2109","arg2_id":"2114","normalized":[]},{"id":"2124","type":"CID","arg1_id":"2111","arg2_id":"2114","normalized":[]},{"id":"2125","type":"CID","arg1_id":"2113","arg2_id":"2114","normalized":[]},{"id":"2126","type":"CID","arg1_id":"2117","arg2_id":"2114","normalized":[]},{"id":"2127","type":"CID","arg1_id":"2109","arg2_id":"2116","normalized":[]},{"id":"2128","type":"CID","arg1_id":"2111","arg2_id":"2116","normalized":[]},{"id":"2129","type":"CID","arg1_id":"2113","arg2_id":"2116","normalized":[]},{"id":"2130","type":"CID","arg1_id":"2117","arg2_id":"2116","normalized":[]}]}
{"id":"2131","document_id":"7596955","passages":[{"id":"2132","type":"title","text":["Clinical evaluation on combined administration of oral prostacyclin analogue beraprost and phosphodiesterase inhibitor cilostazol."],"offsets":[[0,130]]},{"id":"2133","type":"abstract","text":["Among various oral antiplatelets, a combination of a novel prostacyclin analogue beraprost (BPT) and a potent phosphodiesterase inhibitor cilostazol (CLZ) may result in untoward clinical effects due to possible synergistic elevation of intracellular cAMP (cyclic adenosine 3',5'-monophosphate). Thereby, a clinical study of the combined administration of the two agents was attempted. Twelve healthy volunteers were assigned to take BPT\/CLZ in the following schedule; BPT: 40 micrograms at day 1 and 120 micrograms t.i.d. from day 7 to 14, CLZ: 200 mg t.i.d. from day 3 to 14. At various time intervals, physical examination and blood collection for ex vivo platelet aggregation and determination of intraplatelet cAMP were performed. Throughout the observation period, no significant alteration in vital signs was observed. Seven out of 12 subjects experienced headache of a short duration accompanying facial flush in one and nausea in one, especially after ingestion of CLZ. All of these symptoms, probably caused by the vasodilating effect of the two agents, were of mild degree and no special treatment was required. Intraplatelet cAMP content was gradually but significantly increased to 9.84 +\/- 4.59 pmol per 10(9) platelets at day 14 in comparison with the initial value (6.87 +\/- 2.25 pmol). The platelet aggregability was significantly suppressed at various time intervals but no additive or synergistic inhibitory effect by the combined administration was noted. In conclusion, the combined administration of BPT\/CLZ is safe at doses used in the study, though the beneficial clinical effect of the combined administration has yet to be elucidated."],"offsets":[[131,1790]]}],"entities":[{"id":"2134","type":"Chemical","text":["prostacyclin"],"offsets":[[55,67]],"normalized":[{"db_name":"MESH","db_id":"D011464"}]},{"id":"2135","type":"Chemical","text":["beraprost"],"offsets":[[77,86]],"normalized":[{"db_name":"MESH","db_id":"C048081"}]},{"id":"2136","type":"Chemical","text":["cilostazol"],"offsets":[[119,129]],"normalized":[{"db_name":"MESH","db_id":"C045645"}]},{"id":"2137","type":"Chemical","text":["prostacyclin"],"offsets":[[190,202]],"normalized":[{"db_name":"MESH","db_id":"D011464"}]},{"id":"2138","type":"Chemical","text":["beraprost"],"offsets":[[212,221]],"normalized":[{"db_name":"MESH","db_id":"C048081"}]},{"id":"2139","type":"Chemical","text":["BPT"],"offsets":[[223,226]],"normalized":[{"db_name":"MESH","db_id":"C048081"}]},{"id":"2140","type":"Chemical","text":["cilostazol"],"offsets":[[269,279]],"normalized":[{"db_name":"MESH","db_id":"C045645"}]},{"id":"2141","type":"Chemical","text":["CLZ"],"offsets":[[281,284]],"normalized":[{"db_name":"MESH","db_id":"C045645"}]},{"id":"2142","type":"Chemical","text":["cAMP"],"offsets":[[381,385]],"normalized":[{"db_name":"MESH","db_id":"D000242"}]},{"id":"2143","type":"Chemical","text":["cyclic adenosine 3',5'-monophosphate"],"offsets":[[387,423]],"normalized":[{"db_name":"MESH","db_id":"D000242"}]},{"id":"2144","type":"Chemical","text":["BPT"],"offsets":[[564,567]],"normalized":[{"db_name":"MESH","db_id":"C048081"}]},{"id":"2145","type":"Chemical","text":["CLZ"],"offsets":[[568,571]],"normalized":[{"db_name":"MESH","db_id":"C045645"}]},{"id":"2146","type":"Chemical","text":["BPT"],"offsets":[[599,602]],"normalized":[{"db_name":"MESH","db_id":"C048081"}]},{"id":"2147","type":"Chemical","text":["CLZ"],"offsets":[[671,674]],"normalized":[{"db_name":"MESH","db_id":"C045645"}]},{"id":"2148","type":"Disease","text":["platelet aggregation"],"offsets":[[789,809]],"normalized":[{"db_name":"MESH","db_id":"D001791"}]},{"id":"2149","type":"Chemical","text":["cAMP"],"offsets":[[845,849]],"normalized":[{"db_name":"MESH","db_id":"D000242"}]},{"id":"2150","type":"Disease","text":["headache"],"offsets":[[993,1001]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"2151","type":"Disease","text":["facial flush"],"offsets":[[1035,1047]],"normalized":[{"db_name":"MESH","db_id":"D005483"}]},{"id":"2152","type":"Disease","text":["nausea"],"offsets":[[1059,1065]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"2153","type":"Chemical","text":["CLZ"],"offsets":[[1104,1107]],"normalized":[{"db_name":"MESH","db_id":"C045645"}]},{"id":"2154","type":"Chemical","text":["cAMP"],"offsets":[[1267,1271]],"normalized":[{"db_name":"MESH","db_id":"D000242"}]},{"id":"2155","type":"Chemical","text":["BPT"],"offsets":[[1652,1655]],"normalized":[{"db_name":"MESH","db_id":"C048081"}]},{"id":"2156","type":"Chemical","text":["CLZ"],"offsets":[[1656,1659]],"normalized":[{"db_name":"MESH","db_id":"C045645"}]}],"events":[],"coreferences":[],"relations":[{"id":"2157","type":"CID","arg1_id":"2136","arg2_id":"2151","normalized":[]},{"id":"2158","type":"CID","arg1_id":"2140","arg2_id":"2151","normalized":[]},{"id":"2159","type":"CID","arg1_id":"2141","arg2_id":"2151","normalized":[]},{"id":"2160","type":"CID","arg1_id":"2145","arg2_id":"2151","normalized":[]},{"id":"2161","type":"CID","arg1_id":"2147","arg2_id":"2151","normalized":[]},{"id":"2162","type":"CID","arg1_id":"2153","arg2_id":"2151","normalized":[]},{"id":"2163","type":"CID","arg1_id":"2156","arg2_id":"2151","normalized":[]},{"id":"2164","type":"CID","arg1_id":"2136","arg2_id":"2152","normalized":[]},{"id":"2165","type":"CID","arg1_id":"2140","arg2_id":"2152","normalized":[]},{"id":"2166","type":"CID","arg1_id":"2141","arg2_id":"2152","normalized":[]},{"id":"2167","type":"CID","arg1_id":"2145","arg2_id":"2152","normalized":[]},{"id":"2168","type":"CID","arg1_id":"2147","arg2_id":"2152","normalized":[]},{"id":"2169","type":"CID","arg1_id":"2153","arg2_id":"2152","normalized":[]},{"id":"2170","type":"CID","arg1_id":"2156","arg2_id":"2152","normalized":[]},{"id":"2171","type":"CID","arg1_id":"2135","arg2_id":"2150","normalized":[]},{"id":"2172","type":"CID","arg1_id":"2138","arg2_id":"2150","normalized":[]},{"id":"2173","type":"CID","arg1_id":"2139","arg2_id":"2150","normalized":[]},{"id":"2174","type":"CID","arg1_id":"2144","arg2_id":"2150","normalized":[]},{"id":"2175","type":"CID","arg1_id":"2146","arg2_id":"2150","normalized":[]},{"id":"2176","type":"CID","arg1_id":"2155","arg2_id":"2150","normalized":[]},{"id":"2177","type":"CID","arg1_id":"2135","arg2_id":"2151","normalized":[]},{"id":"2178","type":"CID","arg1_id":"2138","arg2_id":"2151","normalized":[]},{"id":"2179","type":"CID","arg1_id":"2139","arg2_id":"2151","normalized":[]},{"id":"2180","type":"CID","arg1_id":"2144","arg2_id":"2151","normalized":[]},{"id":"2181","type":"CID","arg1_id":"2146","arg2_id":"2151","normalized":[]},{"id":"2182","type":"CID","arg1_id":"2155","arg2_id":"2151","normalized":[]},{"id":"2183","type":"CID","arg1_id":"2136","arg2_id":"2150","normalized":[]},{"id":"2184","type":"CID","arg1_id":"2140","arg2_id":"2150","normalized":[]},{"id":"2185","type":"CID","arg1_id":"2141","arg2_id":"2150","normalized":[]},{"id":"2186","type":"CID","arg1_id":"2145","arg2_id":"2150","normalized":[]},{"id":"2187","type":"CID","arg1_id":"2147","arg2_id":"2150","normalized":[]},{"id":"2188","type":"CID","arg1_id":"2153","arg2_id":"2150","normalized":[]},{"id":"2189","type":"CID","arg1_id":"2156","arg2_id":"2150","normalized":[]},{"id":"2190","type":"CID","arg1_id":"2135","arg2_id":"2152","normalized":[]},{"id":"2191","type":"CID","arg1_id":"2138","arg2_id":"2152","normalized":[]},{"id":"2192","type":"CID","arg1_id":"2139","arg2_id":"2152","normalized":[]},{"id":"2193","type":"CID","arg1_id":"2144","arg2_id":"2152","normalized":[]},{"id":"2194","type":"CID","arg1_id":"2146","arg2_id":"2152","normalized":[]},{"id":"2195","type":"CID","arg1_id":"2155","arg2_id":"2152","normalized":[]}]}
{"id":"2196","document_id":"17965424","passages":[{"id":"2197","type":"title","text":["Gastrointestinal tolerability of etoricoxib in rheumatoid arthritis patients: results of the etoricoxib vs diclofenac sodium gastrointestinal tolerability and effectiveness trial (EDGE-II)."],"offsets":[[0,189]]},{"id":"2198","type":"abstract","text":["OBJECTIVE: A randomised, double-blind study to compare the gastrointestinal (GI) tolerability, safety and efficacy of etoricoxib and diclofenac in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: A total of 4086 patients (mean age 60.8 years) diagnosed with RA were enrolled and received etoricoxib 90 mg daily (n = 2032) or diclofenac 75 mg twice daily (n = 2054). Use of gastroprotective agents and low-dose aspirin was allowed. The prespecified primary end point consisted of the cumulative rate of patient discontinuations due to clinical and laboratory GI adverse experiences (AEs). General safety was also assessed, including adjudicated thrombotic cardiovascular event data. Efficacy was evaluated using the Patient Global Assessment of Disease Status (PGADS; 0-4 point scale). RESULTS: Mean (SD; maximum) duration of treatment was 19.3 (10.3; 32.9) and 19.1 (10.4; 33.1) months in the etoricoxib and diclofenac groups, respectively. The cumulative discontinuation rate due to GI AEs was significantly lower with etoricoxib than diclofenac (5.2 vs 8.5 events per 100 patient-years, respectively; hazard ratio 0.62 (95% CI: 0.47, 0.81; p<or=0.001)). The incidence of discontinuations for hypertension-related and oedema-related AEs were significantly higher with etoricoxib (2.5% and 1.1% respectively) compared with diclofenac (1.5% and 0.4% respectively; p<0.001 for hypertension and p<0.01 for oedema). Etoricoxib and diclofenac treatment resulted in similar efficacy (PGADS mean changes from baseline -0.62 vs -0.58, respectively). CONCLUSIONS: Etoricoxib 90 mg demonstrated a significantly lower risk for discontinuing treatment due to GI AEs compared with diclofenac 150 mg. Discontinuations from renovascular AEs, although less common than discontinuations from GI AEs, were significantly higher with etoricoxib."],"offsets":[[190,2029]]}],"entities":[{"id":"2199","type":"Chemical","text":["etoricoxib"],"offsets":[[33,43]],"normalized":[{"db_name":"MESH","db_id":"C422649"}]},{"id":"2200","type":"Disease","text":["rheumatoid arthritis"],"offsets":[[47,67]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"2201","type":"Chemical","text":["etoricoxib"],"offsets":[[93,103]],"normalized":[{"db_name":"MESH","db_id":"C422649"}]},{"id":"2202","type":"Chemical","text":["diclofenac sodium"],"offsets":[[107,124]],"normalized":[{"db_name":"MESH","db_id":"D004008"}]},{"id":"2203","type":"Chemical","text":["etoricoxib"],"offsets":[[308,318]],"normalized":[{"db_name":"MESH","db_id":"C422649"}]},{"id":"2204","type":"Chemical","text":["diclofenac"],"offsets":[[323,333]],"normalized":[{"db_name":"MESH","db_id":"D004008"}]},{"id":"2205","type":"Disease","text":["rheumatoid 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{"id":"2294","document_id":"17042884","passages":[{"id":"2295","type":"title","text":["Placebo-level incidence of extrapyramidal symptoms (EPS) with quetiapine in controlled studies of patients with bipolar mania."],"offsets":[[0,126]]},{"id":"2296","type":"abstract","text":["OBJECTIVES: To evaluate extrapyramidal symptoms (EPS), including akathisia, with quetiapine in patients with bipolar mania. METHODS: Data were analyzed from four similarly designed, randomized, double-blind, 3- to 12-week studies. Two studies evaluated quetiapine monotherapy (up to 800 mg\/day) (n = 209) versus placebo (n = 198), with lithium or haloperidol monotherapy as respective active controls. Two studies evaluated quetiapine (up to 800 mg\/day) in combination with a mood stabilizer (lithium or divalproex, QTP + Li\/DVP) (n = 196) compared to placebo and mood stabilizer (PBO + Li\/DVP) (n = 203). Extrapyramidal symptoms were evaluated using the Simpson-Angus Scale (SAS), the Barnes Akathisia Rating Scale (BARS), adverse event reports and anticholinergic drug usage. RESULTS: The incidence of EPS-related adverse events, including akathisia, was no different with quetiapine monotherapy (12.9%) than with placebo (13.1%). Similarly, EPS-related adverse events with QTP + Li\/DVP (21.4%) were no different than with PBO + Li\/DVP (19.2%). Adverse events related to EPS occurred in 59.6% of patients treated with haloperidol (n = 99) monotherapy, whereas 26.5% of patients treated with lithium (n = 98) monotherapy experienced adverse events related to EPS. The incidence of akathisia was low and similar with quetiapine monotherapy (3.3%) and placebo (6.1%), and with QTP + Li\/DVP (3.6%) and PBO + Li\/DVP (4.9%). Lithium was associated with a significantly higher incidence (p < 0.05) of tremor (18.4%) than quetiapine (5.6%); cerebellar tremor, which is a known adverse effect of lithium, may have contributed to the elevated rate of tremor in patients receiving lithium therapy. Haloperidol induced a significantly higher incidence (p < 0.001) of akathisia (33.3% versus 5.9%), tremor (30.3% versus 7.8%), and extrapyramidal syndrome (35.4% versus 5.9%) than quetiapine. No significant differences were observed between quetiapine and placebo on SAS and BARS scores. Anticholinergic use was low and similar with quetiapine or placebo. CONCLUSIONS: In bipolar mania, the incidence of EPS, including akathisia, with quetiapine therapy is similar to that with placebo."],"offsets":[[127,2302]]}],"entities":[{"id":"2297","type":"Disease","text":["extrapyramidal symptoms"],"offsets":[[27,50]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"2298","type":"Disease","text":["EPS"],"offsets":[[52,55]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"2299","type":"Chemical","text":["quetiapine"],"offsets":[[62,72]],"normalized":[{"db_name":"MESH","db_id":"C069541"}]},{"id":"2300","type":"Disease","text":["bipolar mania"],"offsets":[[112,125]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"2301","type":"Disease","text":["extrapyramidal 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{"id":"2596","document_id":"8586822","passages":[{"id":"2597","type":"title","text":["Contribution of the sympathetic nervous system to salt-sensitivity in lifetime captopril-treated spontaneously hypertensive rats."],"offsets":[[0,129]]},{"id":"2598","type":"abstract","text":["OBJECTIVE: To test the hypothesis that, in lifetime captopril-treated spontaneously hypertensive rats (SHR), the sympathetic nervous system contributes importantly to the hypertensive effect of dietary sodium chloride supplementation. METHODS: Male SHR (aged 6 weeks) that had been treated from conception onward with either captopril or vehicle remained on a basal sodium chloride diet or were fed a high sodium chloride diet. After 2 weeks, the rats were subjected to ganglionic blockade and 2 days later, an infusion of clonidine. RESULTS: Lifetime captopril treatment significantly lowered mean arterial pressure in both groups. Intravenous infusion of the ganglionic blocker hexamethonium resulted in a rapid decline in MAP that eliminated the dietary sodium chloride-induced increase in MAP in both groups. Infusion of the central nervous system alpha2-adrenergic receptor agonist clonidine also resulted in a greater reduction in MAP in both groups of SHR that were fed the high (compared with the basal) sodium chloride diet. CONCLUSIONS: In both lifetime captopril-treated and control SHR, the sympathetic nervous system contributes to the pressor effects of a high sodium chloride diet."],"offsets":[[130,1326]]}],"entities":[{"id":"2599","type":"Chemical","text":["captopril"],"offsets":[[79,88]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"2600","type":"Disease","text":["hypertensive"],"offsets":[[111,123]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"2601","type":"Chemical","text":["captopril"],"offsets":[[182,191]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"2602","type":"Disease","text":["hypertensive"],"offsets":[[214,226]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"2603","type":"Disease","text":["hypertensive"],"offsets":[[301,313]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"2604","type":"Chemical","text":["dietary sodium chloride"],"offsets":[[324,347]],"normalized":[{"db_name":"MESH","db_id":"D017673"}]},{"id":"2605","type":"Chemical","text":["captopril"],"offsets":[[455,464]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"2606","type":"Chemical","text":["sodium chloride"],"offsets":[[496,511]],"normalized":[{"db_name":"MESH","db_id":"D012965"}]},{"id":"2607","type":"Chemical","text":["sodium chloride"],"offsets":[[536,551]],"normalized":[{"db_name":"MESH","db_id":"D012965"}]},{"id":"2608","type":"Chemical","text":["clonidine"],"offsets":[[653,662]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"2609","type":"Chemical","text":["captopril"],"offsets":[[682,691]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"2610","type":"Chemical","text":["hexamethonium"],"offsets":[[810,823]],"normalized":[{"db_name":"MESH","db_id":"D018738"}]},{"id":"2611","type":"Chemical","text":["dietary sodium chloride"],"offsets":[[879,902]],"normalized":[{"db_name":"MESH","db_id":"D017673"}]},{"id":"2612","type":"Disease","text":["increase in MAP"],"offsets":[[911,926]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"2613","type":"Chemical","text":["alpha2-adrenergic receptor agonist"],"offsets":[[982,1016]],"normalized":[{"db_name":"MESH","db_id":"D058647"}]},{"id":"2614","type":"Chemical","text":["clonidine"],"offsets":[[1017,1026]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"2615","type":"Chemical","text":["sodium chloride"],"offsets":[[1142,1157]],"normalized":[{"db_name":"MESH","db_id":"D012965"}]},{"id":"2616","type":"Chemical","text":["captopril"],"offsets":[[1194,1203]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"2617","type":"Chemical","text":["sodium chloride"],"offsets":[[1305,1320]],"normalized":[{"db_name":"MESH","db_id":"D012965"}]}],"events":[],"coreferences":[],"relations":[{"id":"2618","type":"CID","arg1_id":"2604","arg2_id":"2600","normalized":[]},{"id":"2619","type":"CID","arg1_id":"2604","arg2_id":"2602","normalized":[]},{"id":"2620","type":"CID","arg1_id":"2604","arg2_id":"2603","normalized":[]},{"id":"2621","type":"CID","arg1_id":"2604","arg2_id":"2612","normalized":[]},{"id":"2622","type":"CID","arg1_id":"2611","arg2_id":"2600","normalized":[]},{"id":"2623","type":"CID","arg1_id":"2611","arg2_id":"2602","normalized":[]},{"id":"2624","type":"CID","arg1_id":"2611","arg2_id":"2603","normalized":[]},{"id":"2625","type":"CID","arg1_id":"2611","arg2_id":"2612","normalized":[]}]}
{"id":"2626","document_id":"3961813","passages":[{"id":"2627","type":"title","text":["Dose-related beneficial and adverse effects of dietary corticosterone on organophosphorus-induced delayed neuropathy in chickens."],"offsets":[[0,129]]},{"id":"2628","type":"abstract","text":["Tri-ortho-tolyl phosphate (TOTP), 360 mg\/kg, po, and 0,0'-diisopropyl phosphorofluoridate (DFP), 1 mg\/kg sc, were administered to adult White Leghorn chickens 24 hr after they were placed on diets containing 0 to 300 ppm corticosterone. Supplemented diets were continued until clinical signs and lesions of delayed neuropathy appeared. Although low concentrations (less than or equal to 50 ppm) of corticosterone had beneficial effects on TOTP-induced neuropathy, greater than or equal to 200 ppm exacerbated clinical signs in chickens given either TOTP or DFP. Neurotoxic esterase activities 24 hr after TOTP or DFP were less than 20% of values measured in chickens not given organophosphorous compounds. Chickens given 200 ppm corticosterone without TOTP or DFP had significantly elevated activity of plasma cholinesterase and significantly inhibited activity of liver carboxylesterase. Degenerating myelinated fibers were also evident in distal levels of the peripheral nerves of chickens given TOTP or DFP."],"offsets":[[130,1140]]}],"entities":[{"id":"2629","type":"Chemical","text":["corticosterone"],"offsets":[[55,69]],"normalized":[{"db_name":"MESH","db_id":"D003345"}]},{"id":"2630","type":"Chemical","text":["organophosphorus"],"offsets":[[73,89]],"normalized":[{"db_name":"MESH","db_id":"D010755"}]},{"id":"2631","type":"Disease","text":["neuropathy"],"offsets":[[106,116]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"2632","type":"Chemical","text":["Tri-ortho-tolyl phosphate"],"offsets":[[130,155]],"normalized":[{"db_name":"MESH","db_id":"C025541"}]},{"id":"2633","type":"Chemical","text":["TOTP"],"offsets":[[157,161]],"normalized":[{"db_name":"MESH","db_id":"C025541"}]},{"id":"2634","type":"Chemical","text":["0,0'-diisopropyl 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{"id":"2705","document_id":"20973483","passages":[{"id":"2706","type":"title","text":["In vivo characterization of a dual adenosine A2A\/A1 receptor antagonist in animal models of Parkinson's disease."],"offsets":[[0,112]]},{"id":"2707","type":"abstract","text":["The in vivo characterization of a dual adenosine A(2A)\/A(1) receptor antagonist in several animal models of Parkinson's disease is described. Discovery and scale-up syntheses of compound 1 are described in detail, highlighting optimization steps that increased the overall yield of 1 from 10.0% to 30.5%. Compound 1 is a potent A(2A)\/A(1) receptor antagonist in vitro (A(2A) K(i) = 4.1 nM; A(1) K(i) = 17.0 nM) that has excellent activity, after oral administration, across a number of animal models of Parkinson's disease including mouse and rat models of haloperidol-induced catalepsy, mouse model of reserpine-induced akinesia, rat 6-hydroxydopamine (6-OHDA) lesion model of drug-induced rotation, and MPTP-treated non-human primate model."],"offsets":[[113,855]]}],"entities":[{"id":"2708","type":"Chemical","text":["adenosine A2A\/A1 receptor antagonist"],"offsets":[[35,71]],"normalized":[{"db_name":"MESH","db_id":"D058915"}]},{"id":"2709","type":"Disease","text":["Parkinson's disease"],"offsets":[[92,111]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"2710","type":"Chemical","text":["adenosine A(2A)\/A(1) receptor antagonist"],"offsets":[[152,192]],"normalized":[{"db_name":"MESH","db_id":"D058915"}]},{"id":"2711","type":"Disease","text":["Parkinson's disease"],"offsets":[[221,240]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"2712","type":"Disease","text":["Parkinson's disease"],"offsets":[[616,635]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"2713","type":"Chemical","text":["haloperidol"],"offsets":[[670,681]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"2714","type":"Disease","text":["catalepsy"],"offsets":[[690,699]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"2715","type":"Chemical","text":["reserpine"],"offsets":[[716,725]],"normalized":[{"db_name":"MESH","db_id":"D012110"}]},{"id":"2716","type":"Disease","text":["akinesia"],"offsets":[[734,742]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"2717","type":"Chemical","text":["6-hydroxydopamine"],"offsets":[[748,765]],"normalized":[{"db_name":"MESH","db_id":"D016627"}]},{"id":"2718","type":"Chemical","text":["6-OHDA"],"offsets":[[767,773]],"normalized":[{"db_name":"MESH","db_id":"D016627"}]},{"id":"2719","type":"Chemical","text":["MPTP"],"offsets":[[818,822]],"normalized":[{"db_name":"MESH","db_id":"D015632"}]}],"events":[],"coreferences":[],"relations":[{"id":"2720","type":"CID","arg1_id":"2715","arg2_id":"2716","normalized":[]},{"id":"2721","type":"CID","arg1_id":"2713","arg2_id":"2714","normalized":[]}]}
{"id":"2722","document_id":"17511042","passages":[{"id":"2723","type":"title","text":["An extremely rare case of delusional parasitosis in a chronic hepatitis C patient during pegylated interferon alpha-2b and ribavirin treatment."],"offsets":[[0,143]]},{"id":"2724","type":"abstract","text":["During treatment of chronic hepatitis C patients with interferon and ribavirin, a lot of side effects are described. Twenty-three percent to 44% of patients develop depression. A minority of patients evolve to psychosis. To the best of our knowledge, no cases of psychogenic parasitosis occurring during interferon therapy have been described in the literature. We present a 49-year-old woman who developed a delusional parasitosis during treatment with pegylated interferon alpha-2b weekly and ribavirin. She complained of seeing parasites and the larvae of fleas in her stools. This could not be confirmed by any technical examination. All the complaints disappeared after stopping pegylated interferon alpha-2b and reappeared after restarting it. She had a complete sustained viral response."],"offsets":[[144,938]]}],"entities":[{"id":"2725","type":"Disease","text":["delusional parasitosis"],"offsets":[[26,48]],"normalized":[{"db_name":"MESH","db_id":"D063726"}]},{"id":"2726","type":"Disease","text":["chronic hepatitis C"],"offsets":[[54,73]],"normalized":[{"db_name":"MESH","db_id":"D019698"}]},{"id":"2727","type":"Chemical","text":["pegylated interferon alpha-2b"],"offsets":[[89,118]],"normalized":[{"db_name":"MESH","db_id":"C417083"}]},{"id":"2728","type":"Chemical","text":["ribavirin"],"offsets":[[123,132]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"2729","type":"Disease","text":["chronic hepatitis C"],"offsets":[[164,183]],"normalized":[{"db_name":"MESH","db_id":"D019698"}]},{"id":"2730","type":"Chemical","text":["ribavirin"],"offsets":[[213,222]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"2731","type":"Disease","text":["depression"],"offsets":[[309,319]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"2732","type":"Disease","text":["psychosis"],"offsets":[[354,363]],"normalized":[{"db_name":"MESH","db_id":"D011605"}]},{"id":"2733","type":"Disease","text":["psychogenic parasitosis"],"offsets":[[407,430]],"normalized":[{"db_name":"MESH","db_id":"D063726"}]},{"id":"2734","type":"Disease","text":["delusional parasitosis"],"offsets":[[553,575]],"normalized":[{"db_name":"MESH","db_id":"D063726"}]},{"id":"2735","type":"Chemical","text":["pegylated interferon alpha-2b"],"offsets":[[598,627]],"normalized":[{"db_name":"MESH","db_id":"C417083"}]},{"id":"2736","type":"Chemical","text":["ribavirin"],"offsets":[[639,648]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"2737","type":"Chemical","text":["pegylated interferon alpha-2b"],"offsets":[[828,857]],"normalized":[{"db_name":"MESH","db_id":"C417083"}]}],"events":[],"coreferences":[],"relations":[{"id":"2738","type":"CID","arg1_id":"2727","arg2_id":"2725","normalized":[]},{"id":"2739","type":"CID","arg1_id":"2727","arg2_id":"2733","normalized":[]},{"id":"2740","type":"CID","arg1_id":"2727","arg2_id":"2734","normalized":[]},{"id":"2741","type":"CID","arg1_id":"2735","arg2_id":"2725","normalized":[]},{"id":"2742","type":"CID","arg1_id":"2735","arg2_id":"2733","normalized":[]},{"id":"2743","type":"CID","arg1_id":"2735","arg2_id":"2734","normalized":[]},{"id":"2744","type":"CID","arg1_id":"2737","arg2_id":"2725","normalized":[]},{"id":"2745","type":"CID","arg1_id":"2737","arg2_id":"2733","normalized":[]},{"id":"2746","type":"CID","arg1_id":"2737","arg2_id":"2734","normalized":[]},{"id":"2747","type":"CID","arg1_id":"2728","arg2_id":"2725","normalized":[]},{"id":"2748","type":"CID","arg1_id":"2728","arg2_id":"2733","normalized":[]},{"id":"2749","type":"CID","arg1_id":"2728","arg2_id":"2734","normalized":[]},{"id":"2750","type":"CID","arg1_id":"2730","arg2_id":"2725","normalized":[]},{"id":"2751","type":"CID","arg1_id":"2730","arg2_id":"2733","normalized":[]},{"id":"2752","type":"CID","arg1_id":"2730","arg2_id":"2734","normalized":[]},{"id":"2753","type":"CID","arg1_id":"2736","arg2_id":"2725","normalized":[]},{"id":"2754","type":"CID","arg1_id":"2736","arg2_id":"2733","normalized":[]},{"id":"2755","type":"CID","arg1_id":"2736","arg2_id":"2734","normalized":[]}]}
{"id":"2756","document_id":"16720068","passages":[{"id":"2757","type":"title","text":["Possible neuroleptic malignant syndrome related to concomitant treatment with paroxetine and alprazolam."],"offsets":[[0,104]]},{"id":"2758","type":"abstract","text":["A 74-year-old man with depressive symptoms was admitted to a psychiatric hospital due to insomnia, loss of appetite, exhaustion, and agitation. Medical treatment was initiated at a daily dose of 20 mg paroxetine and 1.2 mg alprazolam. On the 10th day of paroxetine and alprazolam treatment, the patient exhibited marked psychomotor retardation, disorientation, and severe muscle rigidity with tremors. The patient had a fever (38.2 degrees C), fluctuating blood pressure (between 165\/90 and 130\/70 mg mm Hg), and severe extrapyramidal symptoms. Laboratory tests showed an elevation of creatine phosphokinase (2218 IU\/L), aspartate aminotransferase (134 IU\/L), alanine aminotransferase (78 IU\/L), and BUN (27.9 mg\/ml) levels. The patient received bromocriptine and diazepam to treat his symptoms. 7 days later, the fever disappeared and the patient's serum CPK levels were normalized (175 IU\/L). This patient presented with symptoms of neuroleptic malignant syndrome (NMS), thus demonstrating that NMS-like symptoms can occur after combined paroxetine and alprazolam treatment. The adverse drug reaction score obtained by the Naranjo algorithm was 6 in our case, indicating a probable relationship between the patient's NMS-like adverse symptoms and the combined treatment used in this case. The involvement of physiologic and environmental aspects specific to this patient was suspected. Several risk factors for NMS should be noted in elderly depressive patients whose symptoms often include dehydration, agitation, malnutrition, and exhaustion. Careful therapeutic intervention is necessary in cases involving elderly patients who suffer from depression."],"offsets":[[105,1761]]}],"entities":[{"id":"2759","type":"Disease","text":["neuroleptic malignant syndrome"],"offsets":[[9,39]],"normalized":[{"db_name":"MESH","db_id":"D009459"}]},{"id":"2760","type":"Chemical","text":["paroxetine"],"offsets":[[78,88]],"normalized":[{"db_name":"MESH","db_id":"D017374"}]},{"id":"2761","type":"Chemical","text":["alprazolam"],"offsets":[[93,103]],"normalized":[{"db_name":"MESH","db_id":"D000525"}]},{"id":"2762","type":"Disease","text":["depressive symptoms"],"offsets":[[128,147]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"2763","type":"Disease","text":["psychiatric"],"offsets":[[166,177]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"2764","type":"Disease","text":["insomnia"],"offsets":[[194,202]],"normalized":[{"db_name":"MESH","db_id":"D007319"}]},{"id":"2765","type":"Disease","text":["loss of 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rigidity"],"offsets":[[477,492]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"2773","type":"Disease","text":["tremors"],"offsets":[[498,505]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"2774","type":"Disease","text":["fever"],"offsets":[[525,530]],"normalized":[{"db_name":"MESH","db_id":"D005334"}]},{"id":"2775","type":"Disease","text":["extrapyramidal 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syndrome"],"offsets":[[1040,1070]],"normalized":[{"db_name":"MESH","db_id":"D009459"}]},{"id":"2783","type":"Disease","text":["NMS"],"offsets":[[1072,1075]],"normalized":[{"db_name":"MESH","db_id":"D009459"}]},{"id":"2784","type":"Disease","text":["NMS"],"offsets":[[1102,1105]],"normalized":[{"db_name":"MESH","db_id":"D009459"}]},{"id":"2785","type":"Chemical","text":["paroxetine"],"offsets":[[1145,1155]],"normalized":[{"db_name":"MESH","db_id":"D017374"}]},{"id":"2786","type":"Chemical","text":["alprazolam"],"offsets":[[1160,1170]],"normalized":[{"db_name":"MESH","db_id":"D000525"}]},{"id":"2787","type":"Disease","text":["NMS"],"offsets":[[1324,1327]],"normalized":[{"db_name":"MESH","db_id":"D009459"}]},{"id":"2788","type":"Disease","text":["NMS"],"offsets":[[1518,1521]],"normalized":[{"db_name":"MESH","db_id":"D009459"}]},{"id":"2789","type":"Disease","text":["depressive"],"offsets":[[1549,1559]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"2790","type":"Disease","text":["dehydration"],"offsets":[[1598,1609]],"normalized":[{"db_name":"MESH","db_id":"D003681"}]},{"id":"2791","type":"Disease","text":["agitation"],"offsets":[[1611,1620]],"normalized":[{"db_name":"MESH","db_id":"D011595"}]},{"id":"2792","type":"Disease","text":["malnutrition"],"offsets":[[1622,1634]],"normalized":[{"db_name":"MESH","db_id":"D044342"}]},{"id":"2793","type":"Disease","text":["depression"],"offsets":[[1750,1760]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]}],"events":[],"coreferences":[],"relations":[{"id":"2794","type":"CID","arg1_id":"2761","arg2_id":"2759","normalized":[]},{"id":"2795","type":"CID","arg1_id":"2761","arg2_id":"2782","normalized":[]},{"id":"2796","type":"CID","arg1_id":"2761","arg2_id":"2783","normalized":[]},{"id":"2797","type":"CID","arg1_id":"2761","arg2_id":"2784","normalized":[]},{"id":"2798","type":"CID","arg1_id":"2761","arg2_id":"2787","normalized":[]},{"id":"2799","type":"CID","arg1_id":"2761","arg2_id":"2788","normalized":[]},{"id":"2800","type":"CID","arg1_id":"2768","arg2_id":"2759","normalized":[]},{"id":"2801","type":"CID","arg1_id":"2768","arg2_id":"2782","normalized":[]},{"id":"2802","type":"CID","arg1_id":"2768","arg2_id":"2783","normalized":[]},{"id":"2803","type":"CID","arg1_id":"2768","arg2_id":"2784","normalized":[]},{"id":"2804","type":"CID","arg1_id":"2768","arg2_id":"2787","normalized":[]},{"id":"2805","type":"CID","arg1_id":"2768","arg2_id":"2788","normalized":[]},{"id":"2806","type":"CID","arg1_id":"2770","arg2_id":"2759","normalized":[]},{"id":"2807","type":"CID","arg1_id":"2770","arg2_id":"2782","normalized":[]},{"id":"2808","type":"CID","arg1_id":"2770","arg2_id":"2783","normalized":[]},{"id":"2809","type":"CID","arg1_id":"2770","arg2_id":"2784","normalized":[]},{"id":"2810","type":"CID","arg1_id":"2770","arg2_id":"2787","normalized":[]},{"id":"2811","type":"CID","arg1_id":"2770","arg2_id":"2788","normalized":[]},{"id":"2812","type":"CID","arg1_id":"2786","arg2_id":"2759","normalized":[]},{"id":"2813","type":"CID","arg1_id":"2786","arg2_id":"2782","normalized":[]},{"id":"2814","type":"CID","arg1_id":"2786","arg2_id":"2783","normalized":[]},{"id":"2815","type":"CID","arg1_id":"2786","arg2_id":"2784","normalized":[]},{"id":"2816","type":"CID","arg1_id":"2786","arg2_id":"2787","normalized":[]},{"id":"2817","type":"CID","arg1_id":"2786","arg2_id":"2788","normalized":[]},{"id":"2818","type":"CID","arg1_id":"2760","arg2_id":"2759","normalized":[]},{"id":"2819","type":"CID","arg1_id":"2760","arg2_id":"2782","normalized":[]},{"id":"2820","type":"CID","arg1_id":"2760","arg2_id":"2783","normalized":[]},{"id":"2821","type":"CID","arg1_id":"2760","arg2_id":"2784","normalized":[]},{"id":"2822","type":"CID","arg1_id":"2760","arg2_id":"2787","normalized":[]},{"id":"2823","type":"CID","arg1_id":"2760","arg2_id":"2788","normalized":[]},{"id":"2824","type":"CID","arg1_id":"2767","arg2_id":"2759","normalized":[]},{"id":"2825","type":"CID","arg1_id":"2767","arg2_id":"2782","normalized":[]},{"id":"2826","type":"CID","arg1_id":"2767","arg2_id":"2783","normalized":[]},{"id":"2827","type":"CID","arg1_id":"2767","arg2_id":"2784","normalized":[]},{"id":"2828","type":"CID","arg1_id":"2767","arg2_id":"2787","normalized":[]},{"id":"2829","type":"CID","arg1_id":"2767","arg2_id":"2788","normalized":[]},{"id":"2830","type":"CID","arg1_id":"2769","arg2_id":"2759","normalized":[]},{"id":"2831","type":"CID","arg1_id":"2769","arg2_id":"2782","normalized":[]},{"id":"2832","type":"CID","arg1_id":"2769","arg2_id":"2783","normalized":[]},{"id":"2833","type":"CID","arg1_id":"2769","arg2_id":"2784","normalized":[]},{"id":"2834","type":"CID","arg1_id":"2769","arg2_id":"2787","normalized":[]},{"id":"2835","type":"CID","arg1_id":"2769","arg2_id":"2788","normalized":[]},{"id":"2836","type":"CID","arg1_id":"2785","arg2_id":"2759","normalized":[]},{"id":"2837","type":"CID","arg1_id":"2785","arg2_id":"2782","normalized":[]},{"id":"2838","type":"CID","arg1_id":"2785","arg2_id":"2783","normalized":[]},{"id":"2839","type":"CID","arg1_id":"2785","arg2_id":"2784","normalized":[]},{"id":"2840","type":"CID","arg1_id":"2785","arg2_id":"2787","normalized":[]},{"id":"2841","type":"CID","arg1_id":"2785","arg2_id":"2788","normalized":[]}]}
{"id":"2842","document_id":"16596970","passages":[{"id":"2843","type":"title","text":["Pilocarpine seizures cause age-dependent impairment in auditory location discrimination."],"offsets":[[0,88]]},{"id":"2844","type":"abstract","text":["Children who have status epilepticus have continuous or rapidly repeating seizures that may be life-threatening and may cause life-long changes in brain and behavior. The extent to which status epilepticus causes deficits in auditory discrimination is unknown. A naturalistic auditory location discrimination method was used to evaluate this question using an animal model of status epilepticus. Male Sprague-Dawley rats were injected with saline on postnatal day (P) 20, or a convulsant dose of pilocarpine on P20 or P45. Pilocarpine on either day induced status epilepticus; status epilepticus at P45 resulted in CA3 cell loss and spontaneous seizures, whereas P20 rats had no cell loss or spontaneous seizures. Mature rats were trained with sound-source location and sound-silence discriminations. Control (saline P20) rats acquired both discriminations immediately. In status epilepticus (P20) rats, acquisition of the sound-source location discrimination was moderately impaired. Status epilepticus (P45) rats failed to acquire either sound-source location or sound-silence discriminations. Status epilepticus in rat causes an age-dependent, long-term impairment in auditory discrimination. This impairment may explain one cause of impaired auditory location discrimination in humans."],"offsets":[[89,1378]]}],"entities":[{"id":"2845","type":"Chemical","text":["Pilocarpine"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"2846","type":"Disease","text":["seizures"],"offsets":[[12,20]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"2847","type":"Disease","text":["impairment in auditory location discrimination"],"offsets":[[41,87]],"normalized":[{"db_name":"MESH","db_id":"D001308"}]},{"id":"2848","type":"Disease","text":["status epilepticus"],"offsets":[[107,125]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"2849","type":"Disease","text":["seizures"],"offsets":[[163,171]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"2850","type":"Disease","text":["status epilepticus"],"offsets":[[276,294]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"2851","type":"Disease","text":["deficits in auditory discrimination"],"offsets":[[302,337]],"normalized":[{"db_name":"MESH","db_id":"D001308"}]},{"id":"2852","type":"Disease","text":["status epilepticus"],"offsets":[[465,483]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"2853","type":"Chemical","text":["pilocarpine"],"offsets":[[585,596]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"2854","type":"Chemical","text":["Pilocarpine"],"offsets":[[612,623]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"2855","type":"Disease","text":["status epilepticus"],"offsets":[[646,664]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"2856","type":"Disease","text":["status epilepticus"],"offsets":[[666,684]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"2857","type":"Disease","text":["seizures"],"offsets":[[734,742]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"2858","type":"Disease","text":["seizures"],"offsets":[[793,801]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"2859","type":"Disease","text":["status epilepticus"],"offsets":[[962,980]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"2860","type":"Disease","text":["Status epilepticus"],"offsets":[[1074,1092]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"2861","type":"Disease","text":["Status epilepticus"],"offsets":[[1185,1203]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"2862","type":"Disease","text":["impairment in auditory discrimination"],"offsets":[[1246,1283]],"normalized":[{"db_name":"MESH","db_id":"D001308"}]},{"id":"2863","type":"Disease","text":["impaired auditory location discrimination"],"offsets":[[1326,1367]],"normalized":[{"db_name":"MESH","db_id":"D001308"}]}],"events":[],"coreferences":[],"relations":[{"id":"2864","type":"CID","arg1_id":"2845","arg2_id":"2848","normalized":[]},{"id":"2865","type":"CID","arg1_id":"2845","arg2_id":"2850","normalized":[]},{"id":"2866","type":"CID","arg1_id":"2845","arg2_id":"2852","normalized":[]},{"id":"2867","type":"CID","arg1_id":"2845","arg2_id":"2855","normalized":[]},{"id":"2868","type":"CID","arg1_id":"2845","arg2_id":"2856","normalized":[]},{"id":"2869","type":"CID","arg1_id":"2845","arg2_id":"2859","normalized":[]},{"id":"2870","type":"CID","arg1_id":"2845","arg2_id":"2860","normalized":[]},{"id":"2871","type":"CID","arg1_id":"2845","arg2_id":"2861","normalized":[]},{"id":"2872","type":"CID","arg1_id":"2853","arg2_id":"2848","normalized":[]},{"id":"2873","type":"CID","arg1_id":"2853","arg2_id":"2850","normalized":[]},{"id":"2874","type":"CID","arg1_id":"2853","arg2_id":"2852","normalized":[]},{"id":"2875","type":"CID","arg1_id":"2853","arg2_id":"2855","normalized":[]},{"id":"2876","type":"CID","arg1_id":"2853","arg2_id":"2856","normalized":[]},{"id":"2877","type":"CID","arg1_id":"2853","arg2_id":"2859","normalized":[]},{"id":"2878","type":"CID","arg1_id":"2853","arg2_id":"2860","normalized":[]},{"id":"2879","type":"CID","arg1_id":"2853","arg2_id":"2861","normalized":[]},{"id":"2880","type":"CID","arg1_id":"2854","arg2_id":"2848","normalized":[]},{"id":"2881","type":"CID","arg1_id":"2854","arg2_id":"2850","normalized":[]},{"id":"2882","type":"CID","arg1_id":"2854","arg2_id":"2852","normalized":[]},{"id":"2883","type":"CID","arg1_id":"2854","arg2_id":"2855","normalized":[]},{"id":"2884","type":"CID","arg1_id":"2854","arg2_id":"2856","normalized":[]},{"id":"2885","type":"CID","arg1_id":"2854","arg2_id":"2859","normalized":[]},{"id":"2886","type":"CID","arg1_id":"2854","arg2_id":"2860","normalized":[]},{"id":"2887","type":"CID","arg1_id":"2854","arg2_id":"2861","normalized":[]},{"id":"2888","type":"CID","arg1_id":"2845","arg2_id":"2847","normalized":[]},{"id":"2889","type":"CID","arg1_id":"2845","arg2_id":"2851","normalized":[]},{"id":"2890","type":"CID","arg1_id":"2845","arg2_id":"2862","normalized":[]},{"id":"2891","type":"CID","arg1_id":"2845","arg2_id":"2863","normalized":[]},{"id":"2892","type":"CID","arg1_id":"2853","arg2_id":"2847","normalized":[]},{"id":"2893","type":"CID","arg1_id":"2853","arg2_id":"2851","normalized":[]},{"id":"2894","type":"CID","arg1_id":"2853","arg2_id":"2862","normalized":[]},{"id":"2895","type":"CID","arg1_id":"2853","arg2_id":"2863","normalized":[]},{"id":"2896","type":"CID","arg1_id":"2854","arg2_id":"2847","normalized":[]},{"id":"2897","type":"CID","arg1_id":"2854","arg2_id":"2851","normalized":[]},{"id":"2898","type":"CID","arg1_id":"2854","arg2_id":"2862","normalized":[]},{"id":"2899","type":"CID","arg1_id":"2854","arg2_id":"2863","normalized":[]}]}
{"id":"2900","document_id":"16586083","passages":[{"id":"2901","type":"title","text":["Cardiovascular risk with cyclooxygenase inhibitors: general problem with substance specific differences?"],"offsets":[[0,104]]},{"id":"2902","type":"abstract","text":["Randomised clinical trials and observational studies have shown an increased risk of myocardial infarction, stroke, hypertension and heart failure during treatment with cyclooxygenase inhibitors. Adverse cardiovascular effects occurred mainly, but not exclusively, in patients with concomitant risk factors. Cyclooxygenase inhibitors cause complex changes in renal, vascular and cardiac prostanoid profiles thereby increasing vascular resistance and fluid retention. The incidence of cardiovascular adverse events tends to increase with the daily dose and total exposure time. A comparison of individual selective and unselective cyclooxygenase inhibitors suggests substance-specific differences, which may depend on differences in pharmacokinetic parameters or inhibitory potency and may be contributed by prostaglandin-independent effects. Diagnostic markers such as N-terminal pro brain natriuretic peptide (NT-proBNP) or high-sensitive C-reactive protein might help in the early identification of patients at risk, thus avoiding the occurrence of serious cardiovascular toxicity."],"offsets":[[105,1188]]}],"entities":[{"id":"2903","type":"Chemical","text":["cyclooxygenase inhibitors"],"offsets":[[25,50]],"normalized":[{"db_name":"MESH","db_id":"D016861"}]},{"id":"2904","type":"Disease","text":["myocardial infarction"],"offsets":[[190,211]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"2905","type":"Disease","text":["stroke"],"offsets":[[213,219]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"2906","type":"Disease","text":["hypertension"],"offsets":[[221,233]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"2907","type":"Disease","text":["heart failure"],"offsets":[[238,251]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"2908","type":"Chemical","text":["cyclooxygenase inhibitors"],"offsets":[[274,299]],"normalized":[{"db_name":"MESH","db_id":"D016861"}]},{"id":"2909","type":"Chemical","text":["Cyclooxygenase inhibitors"],"offsets":[[413,438]],"normalized":[{"db_name":"MESH","db_id":"D016861"}]},{"id":"2910","type":"Chemical","text":["cyclooxygenase inhibitors"],"offsets":[[735,760]],"normalized":[{"db_name":"MESH","db_id":"D016861"}]},{"id":"2911","type":"Chemical","text":["prostaglandin"],"offsets":[[912,925]],"normalized":[{"db_name":"MESH","db_id":"D011453"}]},{"id":"2912","type":"Chemical","text":["N-terminal pro brain natriuretic peptide"],"offsets":[[974,1014]],"normalized":[{"db_name":"MESH","db_id":"C109794"}]},{"id":"2913","type":"Chemical","text":["NT-proBNP"],"offsets":[[1016,1025]],"normalized":[{"db_name":"MESH","db_id":"C109794"}]},{"id":"2914","type":"Disease","text":["cardiovascular toxicity"],"offsets":[[1164,1187]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]}],"events":[],"coreferences":[],"relations":[{"id":"2915","type":"CID","arg1_id":"2903","arg2_id":"2906","normalized":[]},{"id":"2916","type":"CID","arg1_id":"2908","arg2_id":"2906","normalized":[]},{"id":"2917","type":"CID","arg1_id":"2909","arg2_id":"2906","normalized":[]},{"id":"2918","type":"CID","arg1_id":"2910","arg2_id":"2906","normalized":[]},{"id":"2919","type":"CID","arg1_id":"2903","arg2_id":"2905","normalized":[]},{"id":"2920","type":"CID","arg1_id":"2908","arg2_id":"2905","normalized":[]},{"id":"2921","type":"CID","arg1_id":"2909","arg2_id":"2905","normalized":[]},{"id":"2922","type":"CID","arg1_id":"2910","arg2_id":"2905","normalized":[]},{"id":"2923","type":"CID","arg1_id":"2903","arg2_id":"2904","normalized":[]},{"id":"2924","type":"CID","arg1_id":"2908","arg2_id":"2904","normalized":[]},{"id":"2925","type":"CID","arg1_id":"2909","arg2_id":"2904","normalized":[]},{"id":"2926","type":"CID","arg1_id":"2910","arg2_id":"2904","normalized":[]},{"id":"2927","type":"CID","arg1_id":"2903","arg2_id":"2907","normalized":[]},{"id":"2928","type":"CID","arg1_id":"2908","arg2_id":"2907","normalized":[]},{"id":"2929","type":"CID","arg1_id":"2909","arg2_id":"2907","normalized":[]},{"id":"2930","type":"CID","arg1_id":"2910","arg2_id":"2907","normalized":[]}]}
{"id":"2931","document_id":"10539815","passages":[{"id":"2932","type":"title","text":["Predictors of decreased renal function in patients with heart failure during angiotensin-converting enzyme inhibitor therapy: results from the studies of left ventricular dysfunction (SOLVD)"],"offsets":[[0,190]]},{"id":"2933","type":"abstract","text":["BACKGROUND: Although angiotensin-converting enzyme inhibitor therapy reduces mortality rates in patients with congestive heart failure (CHF), it may also cause decreased renal function. Little information is available to predict which patients are at highest risk for this complication. OBJECTIVE: To quantify specific clinical predictors of reduction in renal function in patients with CHF who are prescribed angiotensin-converting enzyme inhibitor therapy. METHOD: We analyzed data from the Studies of Left Ventricular Dysfunction (SOLVD), a randomized, double-blind, placebo-controlled trial of enalapril for the treatment of CHF. There were 3379 patients randomly assigned to enalapril with a median follow-up of 974 days and 3379 patients randomly assigned to placebo with a mean follow-up of 967 days. Decreased renal function was defined as a rise in serum creatinine >\/=0.5 mg\/dL (44 micromol\/L) from baseline. We used time-to-event analysis to identify potential predictors of decrease in renal function including age, baseline ejection fraction, baseline creatinine, low systolic blood pressure (<100 mm Hg), history of hypertension, diabetes, and use of antiplatelet, diuretic, and beta-blocker therapy. RESULTS: Patients randomly assigned to enalapril had a 33% greater likelihood of decreased renal function than controls (P =.003). By multivariate analysis, in both the placebo and enalapril groups older age, diuretic therapy, and diabetes were associated with decreased renal function, whereas beta-blocker therapy and higher ejection fraction were renoprotective. Older age was associated with a greater risk of developing decreased renal function in both groups, but significantly more so in the enalapril group (enalapril: risk ratio [RR] 1.42 per 10 years, 95% confidence interval [CI] 1.32-1.52 with enalapril; placebo: RR 1.18, 95% CI 1.12-1.25). Diuretic therapy was likewise associated with a greater risk of decreased renal function in the enalapril group (RR 1.89, 95% CI 1.70-2.08) than in the placebo group (RR 1.35, 95% CI 1.09-1.66). Conversely, enalapril had a relative renoprotective effect (RR 1.33, 95% CI 1.13-1.53) compared with placebo (RR 1.96, 95% CI 1.57-2.44) in patients with diabetes. A lower risk of renal impairment was seen in both groups with beta-blocker therapy (RR 0.70, 95% CI 0.57-0.85) and higher baseline ejection fraction (RR 0.93 per 5% increment, 95% CI 0.91-0. 96). CONCLUSIONS: Enalapril use caused a 33% increase in the risk of decreased renal function in patients with CHF. Diuretic use and advanced age increased this risk. Diabetes was associated with an increased risk of renal impairment in all patients with CHF, but this risk was reduced in the enalapril group compared with the placebo group. beta-Blocker therapy and higher ejection fraction were renoprotective in all patients regardless of therapy."],"offsets":[[191,3060]]}],"entities":[{"id":"2934","type":"Disease","text":["decreased renal function"],"offsets":[[14,38]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"2935","type":"Disease","text":["heart failure"],"offsets":[[56,69]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"2936","type":"Chemical","text":["angiotensin"],"offsets":[[77,88]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"2937","type":"Disease","text":["left ventricular 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{"id":"3144","document_id":"9022662","passages":[{"id":"3145","type":"title","text":["Pemoline induced acute choreoathetosis: case report and review of the literature."],"offsets":[[0,81]]},{"id":"3146","type":"abstract","text":["BACKGROUND: Pemoline is an oxazolidine derivative that is structurally different from amphetamines and used in the treatment of attention deficit disorder. Pemoline has not been commonly associated in the literature as a cause of acute movement disorders. The following case describes two children acutely poisoned with pemoline who experienced profound choreoathetosis. CASE REPORT: Two, 3-year-old male, identical twin siblings presented to the emergency department after found playing with a an empty bottle of pemoline originally containing 59 tablets. The children had a medical history significant for attention deficit disorder previously treated with methylphenidate without success. This was their first day of pemoline therapy. The choreoathetoid movements began 45 min to 1 h after ingestion. The children gave no history of prior movement disorders and there was no family history of movement disorders. The children received gastrointestinal decontamination and high doses of intravenous benzodiazepines in an attempt to control the choreoathetoid movements. Despite treatment, the children continued to have choreoathetosis for approximately 24 hours. Forty-eight hours after admission, the children appeared to be at their baseline and were discharged home. CONCLUSION: Pemoline associated movement disorder has been rarely reported in the acute toxicology literature. The possibility of choreoathetoid movements should be considered in patients presenting after pemoline overdose."],"offsets":[[82,1578]]}],"entities":[{"id":"3147","type":"Chemical","text":["Pemoline"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D010389"}]},{"id":"3148","type":"Disease","text":["choreoathetosis"],"offsets":[[23,38]],"normalized":[{"db_name":"MESH","db_id":"D002819"},{"db_name":"MESH","db_id":"D001264"}]},{"id":"3149","type":"Chemical","text":["Pemoline"],"offsets":[[94,102]],"normalized":[{"db_name":"MESH","db_id":"D010389"}]},{"id":"3150","type":"Chemical","text":["oxazolidine"],"offsets":[[109,120]],"normalized":[{"db_name":"MESH","db_id":"C064210"}]},{"id":"3151","type":"Chemical","text":["amphetamines"],"offsets":[[168,180]],"normalized":[{"db_name":"MESH","db_id":"D000662"}]},{"id":"3152","type":"Disease","text":["attention deficit 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Limited clinical experience with continuous subcutaneous mesna administration suggests it is a safe, practical, and economic method of drug delivery that permits ifosfamide to be administered successfully in the outpatient setting."],"offsets":[[100,968]]}],"entities":[{"id":"3279","type":"Chemical","text":["mesna"],"offsets":[[42,47]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"3280","type":"Chemical","text":["ifosfamide"],"offsets":[[59,69]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"3281","type":"Disease","text":["hemorrhagic cystitis"],"offsets":[[78,98]],"normalized":[{"db_name":"MESH","db_id":"D006470"},{"db_name":"MESH","db_id":"D003556"}]},{"id":"3282","type":"Disease","text":["hemorrhagic"],"offsets":[[78,89]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"3283","type":"Disease","text":["cystitis"],"offsets":[[90,98]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"3284","type":"Disease","text":["Hemorrhagic 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{"id":"3386","document_id":"6323692","passages":[{"id":"3387","type":"title","text":["Modification of drug action by hyperammonemia."],"offsets":[[0,46]]},{"id":"3388","type":"abstract","text":["Pretreatment with ammonium acetate (NH4Ac) (6 mmol\/kg s.c.) approximately doubled the time morphine-treated mice remained on a hot surface and similarly increased muscular incoordination by diazepam, but NH4Ac treatment alone had no effect. Thus, hyperammonemia is capable of altering drug action and must be considered along with impaired drug metabolism in enhanced drug responses associated with liver disease. Experiments in vitro showed that acetylcholine-induced catecholamine release from bovine adrenal medulla is depressed as much as 50% by 0.3 mM NH4Ac and KCl-induced contractions of guinea-pig ileum were inhibited 20% by 5 mM NH4Ac. Addition of excess calcium reversed the depression in both tissues, but calcium-independent catecholamine release by acetaldehyde was not blocked by NH4Ac. These results suggested that ammonia blocks calcium channels. Parallels in the actions of NH4Ac and the calcium channel blocker verapamil support this concept. Both verapamil (10 mg\/kg i.p.) and NH4Ac pretreatment enhanced morphine analgesia- and diazepam-induced muscular incoordination and antagonized amphetamine-induced motor activity, and neither verapamil nor NH4Ac affected the convulsant action of metrazol. The data suggest that hyperammonemia exerts a calcium channel blocking action which enhances the effects of central nervous system depressants and certain opioid analgesics."],"offsets":[[47,1438]]}],"entities":[{"id":"3389","type":"Disease","text":["hyperammonemia"],"offsets":[[31,45]],"normalized":[{"db_name":"MESH","db_id":"D022124"}]},{"id":"3390","type":"Chemical","text":["ammonium 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{"id":"3448","document_id":"20195852","passages":[{"id":"3449","type":"title","text":["Risk of nephropathy after consumption of nonionic contrast media by children undergoing cardiac angiography: a prospective study."],"offsets":[[0,129]]},{"id":"3450","type":"abstract","text":["Despite increasing reports on nonionic contrast media-induced nephropathy (CIN) in hospitalized adult patients during cardiac procedures, the studies in pediatrics are limited, with even less focus on possible predisposing factors and preventive measures for patients undergoing cardiac angiography. This prospective study determined the incidence of CIN for two nonionic contrast media (CM), iopromide and iohexol, among 80 patients younger than 18 years and compared the rates for this complication in relation to the type and dosage of CM and the presence of cyanosis. The 80 patients in the study consecutively received either iopromide (group A, n = 40) or iohexol (group B, n = 40). Serum sodium (Na), potassium (K), and creatinine (Cr) were measured 24 h before angiography as baseline values, then measured again at 12-, 24-, and 48-h intervals after CM use. Urine samples for Na and Cr also were checked at the same intervals. Risk of renal failure, Injury to the kidney, Failure of kidney function, Loss of kidney function, and End-stage renal damage (RIFLE criteria) were used to define CIN and its incidence in the study population. Accordingly, among the 15 CIN patients (18.75%), 7.5% of the patients in group A had increased risk and 3.75% had renal injury, whereas 5% of group B had increased risk and 2.5% had renal injury. Whereas 33.3% of the patients with CIN were among those who received the proper dosage of CM, the percentage increased to 66.6% among those who received larger doses, with a significant difference in the incidence of CIN related to the different dosages of CM (p = 0.014). Among the 15 patients with CIN, 6 had cyanotic congenital heart diseases, but the incidence did not differ significantly from that for the noncyanotic patients (p = 0.243). Although clinically silent, CIN is not rare in pediatrics. The incidence depends on dosage but not on the type of consumed nonionic CM, nor on the presence of cyanosis, and although CIN usually is reversible, more concern is needed for the prevention of such a complication in children."],"offsets":[[130,2203]]}],"entities":[{"id":"3451","type":"Disease","text":["nephropathy"],"offsets":[[8,19]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"3452","type":"Chemical","text":["contrast media"],"offsets":[[50,64]],"normalized":[{"db_name":"MESH","db_id":"D003287"}]},{"id":"3453","type":"Chemical","text":["contrast 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{"id":"3649","document_id":"18997632","passages":[{"id":"3650","type":"title","text":["A case of ventricular tachycardia related to caffeine pretreatment."],"offsets":[[0,67]]},{"id":"3651","type":"abstract","text":["Suboptimal seizure duration is commonly encountered in electroconvulsive therapy practice, especially in older patients with higher seizure thresholds. Intravenous caffeine is commonly used to improve seizure duration and quality in such patients and is generally well tolerated aside from occasional reports of relatively benign ventricular ectopy. We describe a patient with no previous history of cardiac disease or arrhythmia who developed sustained bigeminy and 2 brief runs of ventricular tachycardia after caffeine administration. Although intravenous caffeine is generally well tolerated, the clinician should be aware of the potential for unpredictable and serious ventricular arrhythmias."],"offsets":[[68,766]]}],"entities":[{"id":"3652","type":"Disease","text":["ventricular tachycardia"],"offsets":[[10,33]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"3653","type":"Chemical","text":["caffeine"],"offsets":[[45,53]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"3654","type":"Disease","text":["seizure"],"offsets":[[79,86]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"3655","type":"Disease","text":["seizure"],"offsets":[[200,207]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"3656","type":"Chemical","text":["caffeine"],"offsets":[[232,240]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"3657","type":"Disease","text":["seizure"],"offsets":[[269,276]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"3658","type":"Disease","text":["ventricular ectopy"],"offsets":[[398,416]],"normalized":[{"db_name":"MESH","db_id":"D018879"}]},{"id":"3659","type":"Disease","text":["cardiac disease"],"offsets":[[468,483]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"3660","type":"Disease","text":["arrhythmia"],"offsets":[[487,497]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"3661","type":"Disease","text":["ventricular tachycardia"],"offsets":[[551,574]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"3662","type":"Chemical","text":["caffeine"],"offsets":[[581,589]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"3663","type":"Chemical","text":["caffeine"],"offsets":[[627,635]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"3664","type":"Disease","text":["ventricular arrhythmias"],"offsets":[[742,765]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]}],"events":[],"coreferences":[],"relations":[{"id":"3665","type":"CID","arg1_id":"3653","arg2_id":"3654","normalized":[]},{"id":"3666","type":"CID","arg1_id":"3653","arg2_id":"3655","normalized":[]},{"id":"3667","type":"CID","arg1_id":"3653","arg2_id":"3657","normalized":[]},{"id":"3668","type":"CID","arg1_id":"3656","arg2_id":"3654","normalized":[]},{"id":"3669","type":"CID","arg1_id":"3656","arg2_id":"3655","normalized":[]},{"id":"3670","type":"CID","arg1_id":"3656","arg2_id":"3657","normalized":[]},{"id":"3671","type":"CID","arg1_id":"3662","arg2_id":"3654","normalized":[]},{"id":"3672","type":"CID","arg1_id":"3662","arg2_id":"3655","normalized":[]},{"id":"3673","type":"CID","arg1_id":"3662","arg2_id":"3657","normalized":[]},{"id":"3674","type":"CID","arg1_id":"3663","arg2_id":"3654","normalized":[]},{"id":"3675","type":"CID","arg1_id":"3663","arg2_id":"3655","normalized":[]},{"id":"3676","type":"CID","arg1_id":"3663","arg2_id":"3657","normalized":[]},{"id":"3677","type":"CID","arg1_id":"3653","arg2_id":"3652","normalized":[]},{"id":"3678","type":"CID","arg1_id":"3653","arg2_id":"3661","normalized":[]},{"id":"3679","type":"CID","arg1_id":"3656","arg2_id":"3652","normalized":[]},{"id":"3680","type":"CID","arg1_id":"3656","arg2_id":"3661","normalized":[]},{"id":"3681","type":"CID","arg1_id":"3662","arg2_id":"3652","normalized":[]},{"id":"3682","type":"CID","arg1_id":"3662","arg2_id":"3661","normalized":[]},{"id":"3683","type":"CID","arg1_id":"3663","arg2_id":"3652","normalized":[]},{"id":"3684","type":"CID","arg1_id":"3663","arg2_id":"3661","normalized":[]},{"id":"3685","type":"CID","arg1_id":"3653","arg2_id":"3658","normalized":[]},{"id":"3686","type":"CID","arg1_id":"3656","arg2_id":"3658","normalized":[]},{"id":"3687","type":"CID","arg1_id":"3662","arg2_id":"3658","normalized":[]},{"id":"3688","type":"CID","arg1_id":"3663","arg2_id":"3658","normalized":[]}]}
{"id":"3689","document_id":"15565293","passages":[{"id":"3690","type":"title","text":["Optical coherence tomography can measure axonal loss in patients with ethambutol-induced optic neuropathy."],"offsets":[[0,106]]},{"id":"3691","type":"abstract","text":["PURPOSE: To map and identify the pattern, in vivo, of axonal degeneration in ethambutol-induced optic neuropathy using optical coherence tomography (OCT). Ethambutol is an antimycobacterial agent often used to treat tuberculosis. A serious complication of ethambutol is an optic neuropathy that impairs visual acuity, contrast sensitivity, and color vision. However, early on, when the toxic optic neuropathy is mild and partly reversible, the funduscopic findings are often subtle and easy to miss. METHODS: Three subjects with a history of ethambutol (EMB)-induced optic neuropathy of short-, intermediate-, and long-term visual deficits were administered a full neuro-ophthalmologic examination including visual acuity, color vision, contrast sensitivity, and fundus examination. In addition, OCT (OCT 3000, Humphrey-Zeiss, Dublin, CA) was performed on both eyes of each subject using the retinal nerve fiber layer (RNFL) analysis protocol. OCT interpolates data from 100 points around the optic nerve to effectively map out the RNFL. RESULTS: The results were compared to the calculated average RNFL of normal eyes accumulated from four prior studies using OCT, n=661. In all subjects with history of EMB-induced optic neuropathy, there was a mean loss of 72% nerve fiber layer thickness in the temporal quadrant (patient A, with eventual recovery of visual acuity and fields, 58% loss; patient B, with intermediate visual deficits, 68% loss; patient C, with chronic visual deficits, 90% loss), with an average mean optic nerve thickness of 26+\/-16 microm. There was a combined mean loss of 46% of fibers from the superior, inferior, and nasal quadrants in the (six) eyes of all three subjects (mean average thickness of 55+\/-29 microm). In both sets (four) of eyes of the subjects with persistent visual deficits (patients B and C), there was an average loss of 79% of nerve fiber thickness in the temporal quadrant. CONCLUSIONS: The OCT results in these patients with EMB-induced optic neuropathy show considerable loss especially of the temporal fibers. This is consistent with prior histopathological studies that show predominant loss of parvo-cellular axons (or small-caliber axons) within the papillo-macular bundle in toxic or hereditary optic neuropathies. OCT can be a valuable tool in the quantitative analysis of optic neuropathies. Additionally, in terms of management of EMB-induced optic neuropathy, it is important to properly manage ethambutol dosing in patients with renal impairment and to achieve proper transition to a maintenance dose once an appropriate loading dose has been reached."],"offsets":[[107,2718]]}],"entities":[{"id":"3692","type":"Chemical","text":["ethambutol"],"offsets":[[70,80]],"normalized":[{"db_name":"MESH","db_id":"D004977"}]},{"id":"3693","type":"Disease","text":["optic neuropathy"],"offsets":[[89,105]],"normalized":[{"db_name":"MESH","db_id":"D009901"}]},{"id":"3694","type":"Disease","text":["axonal degeneration"],"offsets":[[161,180]],"normalized":[{"db_name":"MESH","db_id":"D009410"}]},{"id":"3695","type":"Chemical","text":["ethambutol"],"offsets":[[184,194]],"normalized":[{"db_name":"MESH","db_id":"D004977"}]},{"id":"3696","type":"Disease","text":["optic 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{"id":"3859","document_id":"15266215","passages":[{"id":"3860","type":"title","text":["Effects of the cyclooxygenase-2 specific inhibitor valdecoxib versus nonsteroidal antiinflammatory agents and placebo on cardiovascular thrombotic events in patients with arthritis."],"offsets":[[0,181]]},{"id":"3861","type":"abstract","text":["There have been concerns that the risk of cardiovascular thrombotic events may be higher with cyclooxygenase (COX)-2-specific inhibitors than nonselective nonsteroidal antiinflammatory drugs (NSAIDs). We evaluated cardiovascular event data for valdecoxib, a new COX-2-specific inhibitor in approximately 8000 patients with osteoarthritis and rheumatoid arthritis treated with this agent in randomized clinical trials. The incidence of cardiovascular thrombotic events (cardiac, cerebrovascular and peripheral vascular, or arterial thrombotic) was determined by analyzing pooled valdecoxib (10-80 mg daily), nonselective NSAID (diclofenac 75 mg bid, ibuprofen 800 mg tid, or naproxen 500 mg bid) and placebo data from 10 randomized osteoarthritis and rheumatoid arthritis trials that were 6-52 weeks in duration. The incidence rates of events were determined in all patients (n = 7934) and in users of low-dose (< or =325 mg daily) aspirin (n = 1051) and nonusers of aspirin (n = 6883). Crude and exposure-adjusted incidences of thrombotic events were similar for valdecoxib, NSAIDs, and placebo. The risk of serious thrombotic events was also similar for each valdecoxib dose. Thrombotic risk was consistently higher for users of aspirin users than nonusers of aspirin (placebo, 1.4% vs. 0%; valdecoxib, 1.7% vs. 0.2%; NSAIDs, 1.9% vs. 0.5%). The rates of events in users of aspirin were similar for all 3 treatment groups and across valdecoxib doses. Short- and intermediate-term treatment with therapeutic (10 or 20 mg daily) and supratherapeutic (40 or 80 mg daily) valdecoxib doses was not associated with an increased incidence of thrombotic events relative to nonselective NSAIDs or placebo in osteoarthritis and rheumatoid arthritis patients in controlled clinical 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{"id":"3933","document_id":"14742097","passages":[{"id":"3934","type":"title","text":["A randomized, placebo-controlled, crossover study of ephedrine for SSRI-induced female sexual dysfunction."],"offsets":[[0,106]]},{"id":"3935","type":"abstract","text":["The objective of this study was to determine whether ephedrine, an alpha- and beta-adrenergic agonist previously shown to enhance genital blood flow in women, has beneficial effects in reversing antidepressant-induced sexual dysfunction. Nineteen sexually dysfunctional women receiving either fluoxetine, sertraline, or paroxetine participated in an eight-week, double-blind, placebo-controlled, cross-over study of the effects of ephedrine (50 mg) on self-report measures of sexual desire, arousal, orgasm, and sexual satisfaction. Although there were significant improvements relative to baseline in sexual desire and orgasm intensity\/pleasure on 50 mg ephedrine 1-hr prior to sexual activity, significant improvements in these measures, as well as in sexual arousal and orgasmic ability also were noted with placebo. These findings highlight the importance of conducting placebo-controlled trials for this condition."],"offsets":[[107,1026]]}],"entities":[{"id":"3936","type":"Chemical","text":["ephedrine"],"offsets":[[53,62]],"normalized":[{"db_name":"MESH","db_id":"D004809"}]},{"id":"3937","type":"Disease","text":["sexual dysfunction"],"offsets":[[87,105]],"normalized":[{"db_name":"MESH","db_id":"D020018"}]},{"id":"3938","type":"Chemical","text":["ephedrine"],"offsets":[[160,169]],"normalized":[{"db_name":"MESH","db_id":"D004809"}]},{"id":"3939","type":"Disease","text":["sexual dysfunction"],"offsets":[[325,343]],"normalized":[{"db_name":"MESH","db_id":"D020018"}]},{"id":"3940","type":"Disease","text":["sexually dysfunctional"],"offsets":[[354,376]],"normalized":[{"db_name":"MESH","db_id":"D020018"}]},{"id":"3941","type":"Chemical","text":["fluoxetine"],"offsets":[[400,410]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"3942","type":"Chemical","text":["sertraline"],"offsets":[[412,422]],"normalized":[{"db_name":"MESH","db_id":"D020280"}]},{"id":"3943","type":"Chemical","text":["paroxetine"],"offsets":[[427,437]],"normalized":[{"db_name":"MESH","db_id":"D017374"}]},{"id":"3944","type":"Chemical","text":["ephedrine"],"offsets":[[538,547]],"normalized":[{"db_name":"MESH","db_id":"D004809"}]},{"id":"3945","type":"Chemical","text":["ephedrine"],"offsets":[[762,771]],"normalized":[{"db_name":"MESH","db_id":"D004809"}]}],"events":[],"coreferences":[],"relations":[{"id":"3946","type":"CID","arg1_id":"3941","arg2_id":"3937","normalized":[]},{"id":"3947","type":"CID","arg1_id":"3941","arg2_id":"3939","normalized":[]},{"id":"3948","type":"CID","arg1_id":"3941","arg2_id":"3940","normalized":[]},{"id":"3949","type":"CID","arg1_id":"3943","arg2_id":"3937","normalized":[]},{"id":"3950","type":"CID","arg1_id":"3943","arg2_id":"3939","normalized":[]},{"id":"3951","type":"CID","arg1_id":"3943","arg2_id":"3940","normalized":[]},{"id":"3952","type":"CID","arg1_id":"3942","arg2_id":"3937","normalized":[]},{"id":"3953","type":"CID","arg1_id":"3942","arg2_id":"3939","normalized":[]},{"id":"3954","type":"CID","arg1_id":"3942","arg2_id":"3940","normalized":[]}]}
{"id":"3955","document_id":"11890511","passages":[{"id":"3956","type":"title","text":["Erectile dysfunction occurs following substantia nigra lesions in the rat."],"offsets":[[0,74]]},{"id":"3957","type":"abstract","text":["Erectile function was assessed 6 weeks following uni- and bilateral injections of 6-hydroxydopamine in the substantia nigra nucleus of the brain. Behavioral apomorphine-induced penile erections were reduced (5\/8) and increased (3\/8) in uni- and bilateral lesioned animals. Intracavernous pressures, following electrical stimulation of the cavernous nerve, decreased in lesioned animals. Lesions of the substantia nigra were confirmed by histology. Concentration of dopamine and its metabolites were decreased in the striatum of substantia nigra lesioned rats. Lesions of the substantia nigra are therefore associated with erectile dysfunction in rats and may serve as a model to study erectile dysfunction in Parkinson's disease."],"offsets":[[75,804]]}],"entities":[{"id":"3958","type":"Disease","text":["Erectile dysfunction"],"offsets":[[0,20]],"normalized":[{"db_name":"MESH","db_id":"D007172"}]},{"id":"3959","type":"Chemical","text":["6-hydroxydopamine"],"offsets":[[157,174]],"normalized":[{"db_name":"MESH","db_id":"D016627"}]},{"id":"3960","type":"Chemical","text":["apomorphine"],"offsets":[[232,243]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"3961","type":"Chemical","text":["dopamine"],"offsets":[[540,548]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"3962","type":"Disease","text":["erectile dysfunction"],"offsets":[[697,717]],"normalized":[{"db_name":"MESH","db_id":"D007172"}]},{"id":"3963","type":"Disease","text":["erectile dysfunction"],"offsets":[[760,780]],"normalized":[{"db_name":"MESH","db_id":"D007172"}]},{"id":"3964","type":"Disease","text":["Parkinson's disease"],"offsets":[[784,803]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]}],"events":[],"coreferences":[],"relations":[{"id":"3965","type":"CID","arg1_id":"3959","arg2_id":"3958","normalized":[]},{"id":"3966","type":"CID","arg1_id":"3959","arg2_id":"3962","normalized":[]},{"id":"3967","type":"CID","arg1_id":"3959","arg2_id":"3963","normalized":[]}]}
{"id":"3968","document_id":"9270571","passages":[{"id":"3969","type":"title","text":["Potential therapeutic use of the selective dopamine D1 receptor agonist, A-86929: an acute study in parkinsonian levodopa-primed monkeys."],"offsets":[[0,137]]},{"id":"3970","type":"abstract","text":["The clinical utility of dopamine (DA) D1 receptor agonists in the treatment of Parkinson's disease (PD) is still unclear. The therapeutic use of selective DA D1 receptor agonists such as SKF-82958 (6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzaze pine hydrobromide) and A-77636 ([1R, 3S] 3-[1'-admantyl]-1-aminomethyl-3,4-dihydro-5,6-dihydroxy-1H-2-benzo pyran hydrochloride) seems limited because of their duration of action, which is too short for SKF-82958 (< 1 hr) and too long for A-77636 (> 20 hr, leading to behavioral tolerance). We therefore conducted the present acute dose-response study in four 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-exposed cynomolgus monkeys primed to exhibit levodopa-induced dyskinesias to evaluate the locomotor and dyskinetic effects on challenge with four doses (from 0.03 to 1.0 mg\/kg) of A-86929 ([-]-[5aR,11bS]-4,5,5a,6,7,11b-hexahydro-2-propyl-3-thia-5-+ ++azacyclopent-1- ena[c]phenathrene-9-10-diol), a selective and full DA D1-like receptor agonist with an intermediate duration of action. Levodopa and the DA D2-like receptor agonist, LY-171555 ([4aR-trans]-4,4a,5,6,7,8,8a,9-o-dihydro-5n-propyl-2H-pyrazo lo-3-4-quinoline hydrochloride) were also used for comparison. Acute administration of A-86929 was as efficacious in alleviating MPTP-induced parkinsonism as levodopa and LY-171555, but was less likely to reproduce the levodopa-induced dyskinesias in these animals than with either LY-171555 or subsequent challenge of levodopa. Selective stimulation of the DA D1 receptor may provide better integration of neural inputs transmitted to the internal segment of the globus pallidus (referred to as the basal ganglia output) compared with levodopa and selective DA D2 receptor agonist. Potent DA D1 receptor agents with an intermediate duration of efficacy such as A-86929 (approximately 4 hr at higher doses tested) are potential therapeutic tools in PD and merit further attention."],"offsets":[[138,2104]]}],"entities":[{"id":"3971","type":"Chemical","text":["dopamine"],"offsets":[[43,51]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"3972","type":"Chemical","text":["A-86929"],"offsets":[[73,80]],"normalized":[{"db_name":"MESH","db_id":"C095427"}]},{"id":"3973","type":"Disease","text":["parkinsonian"],"offsets":[[100,112]],"normalized":[{"db_name":"MESH","db_id":"D020734"}]},{"id":"3974","type":"Chemical","text":["levodopa"],"offsets":[[113,121]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"3975","type":"Chemical","text":["dopamine"],"offsets":[[162,170]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"3976","type":"Chemical","text":["DA"],"offsets":[[172,174]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"3977","type":"Disease","text":["Parkinson's 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{"id":"4040","document_id":"7189975","passages":[{"id":"4041","type":"title","text":["Deaths from local anesthetic-induced convulsions in mice."],"offsets":[[0,57]]},{"id":"4042","type":"abstract","text":["Median convulsant (CD50) and median lethal (LD50) doses of three representative local anesthetics were determined in adult mice to evaluate the threat to life of local anesthetic-induced convulsions. The CD50 and LD50, respectively, were 57.7 and 58.7 mg\/kg for bupivacaine, 111.0 and 133.1 mg\/kg for lidocaine, and 243.4 and 266.5 mg\/kg for chloroprocaine. When given intraperitoneally, bupivacaine thus was only about twice as toxic as lidocaine and four times as toxic as chloroprocaine. Convulsions always preceded death, except after precipitous cardiopulmonary arrest from extreme doses. A CD50 dose of local anesthetic (causing convulsions in 50% of mice) was fatal in 90% of bupivacaine-induced seizures, in 57% of the chloroprocaine group, and in 6% of the lidocaine group. The narrow gap between convulsant and lethal doses of local anesthetics indicates that untreated convulsions present much more of a threat to life than heretofore appreciated."],"offsets":[[58,1016]]}],"entities":[{"id":"4043","type":"Disease","text":["convulsions"],"offsets":[[37,48]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"4044","type":"Disease","text":["convulsions"],"offsets":[[245,256]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"4045","type":"Chemical","text":["bupivacaine"],"offsets":[[320,331]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"4046","type":"Chemical","text":["lidocaine"],"offsets":[[359,368]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"4047","type":"Chemical","text":["chloroprocaine"],"offsets":[[400,414]],"normalized":[{"db_name":"MESH","db_id":"C004616"}]},{"id":"4048","type":"Chemical","text":["bupivacaine"],"offsets":[[446,457]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"4049","type":"Chemical","text":["lidocaine"],"offsets":[[496,505]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"4050","type":"Chemical","text":["chloroprocaine"],"offsets":[[533,547]],"normalized":[{"db_name":"MESH","db_id":"C004616"}]},{"id":"4051","type":"Disease","text":["Convulsions"],"offsets":[[549,560]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"4052","type":"Disease","text":["cardiopulmonary 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ID","arg1_id":"4054","arg2_id":"4058","normalized":[]}]}
{"id":"4113","document_id":"6415512","passages":[{"id":"4114","type":"title","text":["Myoclonic, atonic, and absence seizures following institution of carbamazepine therapy in children."],"offsets":[[0,99]]},{"id":"4115","type":"abstract","text":["Five children, aged 3 to 11 years, treated with carbamazepine for epilepsy, had an acute aberrant reaction characterized by the onset of myoclonic, atypical absence and\/or atonic (minor motor) seizures within a few days. When the carbamazepine was discontinued, two of the children returned to their former state very quickly, two had the minor motor seizures resolve in 3 and 6 months, and one had the seizures persist. The child in whom the seizures persisted was later found to have ceroid lipofuscinosis. The other children are doing well on other anticonvulsants."],"offsets":[[100,668]]}],"entities":[{"id":"4116","type":"Disease","text":["Myoclonic, atonic, and absence seizures"],"offsets":[[0,39]],"normalized":[{"db_name":"MESH","db_id":"D004831"},{"db_name":"MESH","db_id":"D004832"}]},{"id":"4117","type":"Disease","text":["Myoclonic","seizures"],"offsets":[[0,9],[31,39]],"normalized":[{"db_name":"MESH","db_id":"D004831"}]},{"id":"4118","type":"Disease","text":["absence seizures"],"offsets":[[23,39]],"normalized":[{"db_name":"MESH","db_id":"D004832"}]},{"id":"4119","type":"Chemical","text":["carbamazepine"],"offsets":[[65,78]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"4120","type":"Chemical","text":["carbamazepine"],"offsets":[[148,161]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"4121","type":"Disease","text":["epilepsy"],"offsets":[[166,174]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"4122","type":"Disease","text":["myoclonic, atypical absence and\/or atonic (minor motor) seizures"],"offsets":[[237,301]],"normalized":[{"db_name":"MESH","db_id":"D004831"},{"db_name":"MESH","db_id":"D004832"}]},{"id":"4123","type":"Disease","text":["myoclonic","seizures"],"offsets":[[237,246],[293,301]],"normalized":[{"db_name":"MESH","db_id":"D004831"}]},{"id":"4124","type":"Disease","text":["atypical absence","seizures"],"offsets":[[247,263],[293,301]],"normalized":[{"db_name":"MESH","db_id":"D004832"}]},{"id":"4125","type":"Chemical","text":["carbamazepine"],"offsets":[[330,343]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"4126","type":"Disease","text":["seizures"],"offsets":[[451,459]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"4127","type":"Disease","text":["seizures"],"offsets":[[503,511]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"4128","type":"Disease","text":["seizures"],"offsets":[[543,551]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"4129","type":"Disease","text":["ceroid lipofuscinosis"],"offsets":[[586,607]],"normalized":[{"db_name":"MESH","db_id":"D009472"}]}],"events":[],"coreferences":[],"relations":[{"id":"4130","type":"CID","arg1_id":"4119","arg2_id":"4116","normalized":[]},{"id":"4131","type":"CID","arg1_id":"4119","arg2_id":"4118","normalized":[]},{"id":"4132","type":"CID","arg1_id":"4119","arg2_id":"4122","normalized":[]},{"id":"4133","type":"CID","arg1_id":"4119","arg2_id":"4124","normalized":[]},{"id":"4134","type":"CID","arg1_id":"4120","arg2_id":"4116","normalized":[]},{"id":"4135","type":"CID","arg1_id":"4120","arg2_id":"4118","normalized":[]},{"id":"4136","type":"CID","arg1_id":"4120","arg2_id":"4122","normalized":[]},{"id":"4137","type":"CID","arg1_id":"4120","arg2_id":"4124","normalized":[]},{"id":"4138","type":"CID","arg1_id":"4125","arg2_id":"4116","normalized":[]},{"id":"4139","type":"CID","arg1_id":"4125","arg2_id":"4118","normalized":[]},{"id":"4140","type":"CID","arg1_id":"4125","arg2_id":"4122","normalized":[]},{"id":"4141","type":"CID","arg1_id":"4125","arg2_id":"4124","normalized":[]},{"id":"4142","type":"CID","arg1_id":"4119","arg2_id":"4116","normalized":[]},{"id":"4143","type":"CID","arg1_id":"4119","arg2_id":"4117","normalized":[]},{"id":"4144","type":"CID","arg1_id":"4119","arg2_id":"4122","normalized":[]},{"id":"4145","type":"CID","arg1_id":"4119","arg2_id":"4123","normalized":[]},{"id":"4146","type":"CID","arg1_id":"4120","arg2_id":"4116","normalized":[]},{"id":"4147","type":"CID","arg1_id":"4120","arg2_id":"4117","normalized":[]},{"id":"4148","type":"CID","arg1_id":"4120","arg2_id":"4122","normalized":[]},{"id":"4149","type":"CID","arg1_id":"4120","arg2_id":"4123","normalized":[]},{"id":"4150","type":"CID","arg1_id":"4125","arg2_id":"4116","normalized":[]},{"id":"4151","type":"CID","arg1_id":"4125","arg2_id":"4117","normalized":[]},{"id":"4152","type":"CID","arg1_id":"4125","arg2_id":"4122","normalized":[]},{"id":"4153","type":"CID","arg1_id":"4125","arg2_id":"4123","normalized":[]}]}
{"id":"4154","document_id":"1928887","passages":[{"id":"4155","type":"title","text":["Naloxone reversal of hypotension due to captopril overdose."],"offsets":[[0,59]]},{"id":"4156","type":"abstract","text":["The hemodynamic effects of captopril and other angiotensin-converting enzyme inhibitors may be mediated by the endogenous opioid system. The opioid antagonist naloxone has been shown to block or reverse the hypotensive actions of captopril. We report a case of an intentional captopril overdose, manifested by marked hypotension, that resolved promptly with the administration of naloxone. To our knowledge, this is the first reported case of captopril-induced hypotension treated with naloxone. Our experience demonstrates a possible role of naloxone in the reversal of hypotension resulting from captopril."],"offsets":[[60,668]]}],"entities":[{"id":"4157","type":"Chemical","text":["Naloxone"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"4158","type":"Disease","text":["hypotension"],"offsets":[[21,32]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"4159","type":"Chemical","text":["captopril"],"offsets":[[40,49]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"4160","type":"Disease","text":["overdose"],"offsets":[[50,58]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"4161","type":"Chemical","text":["captopril"],"offsets":[[87,96]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"4162","type":"Chemical","text":["angiotensin-converting enzyme inhibitors"],"offsets":[[107,147]],"normalized":[{"db_name":"MESH","db_id":"D000806"}]},{"id":"4163","type":"Chemical","text":["naloxone"],"offsets":[[219,227]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"4164","type":"Disease","text":["hypotensive"],"offsets":[[267,278]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"4165","type":"Chemical","text":["captopril"],"offsets":[[290,299]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"4166","type":"Chemical","text":["captopril"],"offsets":[[336,345]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"4167","type":"Disease","text":["overdose"],"offsets":[[346,354]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"4168","type":"Disease","text":["hypotension"],"offsets":[[377,388]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"4169","type":"Chemical","text":["naloxone"],"offsets":[[440,448]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"4170","type":"Chemical","text":["captopril"],"offsets":[[503,512]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"4171","type":"Disease","text":["hypotension"],"offsets":[[521,532]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"4172","type":"Chemical","text":["naloxone"],"offsets":[[546,554]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"4173","type":"Chemical","text":["naloxone"],"offsets":[[603,611]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"4174","type":"Disease","text":["hypotension"],"offsets":[[631,642]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"4175","type":"Chemical","text":["captopril"],"offsets":[[658,667]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]}],"events":[],"coreferences":[],"relations":[{"id":"4176","type":"CID","arg1_id":"4162","arg2_id":"4158","normalized":[]},{"id":"4177","type":"CID","arg1_id":"4162","arg2_id":"4164","normalized":[]},{"id":"4178","type":"CID","arg1_id":"4162","arg2_id":"4168","normalized":[]},{"id":"4179","type":"CID","arg1_id":"4162","arg2_id":"4171","normalized":[]},{"id":"4180","type":"CID","arg1_id":"4162","arg2_id":"4174","normalized":[]},{"id":"4181","type":"CID","arg1_id":"4162","arg2_id":"4160","normalized":[]},{"id":"4182","type":"CID","arg1_id":"4162","arg2_id":"4167","normalized":[]}]}
{"id":"4183","document_id":"1728915","passages":[{"id":"4184","type":"title","text":["Carbamazepine-induced cardiac dysfunction. Characterization of two distinct clinical syndromes."],"offsets":[[0,95]]},{"id":"4185","type":"abstract","text":["A patient with sinus bradycardia and atrioventricular block, induced by carbamazepine, prompted an extensive literature review of all previously reported cases. From the analysis of these cases, two distinct forms of carbamazepine-associated cardiac dysfunction emerged. One patient group developed sinus tachycardias in the setting of a massive carbamazepine overdose. The second group consisted almost exclusively of elderly women who developed potentially life-threatening bradyarrhythmias or atrioventricular conduction delay, associated with either therapeutic or modestly elevated carbamazepine serum levels. Because carbamazepine is widely used in the treatment of many neurologic and psychiatric conditions, the recognition of the latter syndrome has important implications for the use of this drug in elderly patients."],"offsets":[[96,923]]}],"entities":[{"id":"4186","type":"Chemical","text":["Carbamazepine"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"4187","type":"Disease","text":["cardiac dysfunction"],"offsets":[[22,41]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"4188","type":"Disease","text":["bradycardia"],"offsets":[[117,128]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"4189","type":"Disease","text":["atrioventricular block"],"offsets":[[133,155]],"normalized":[{"db_name":"MESH","db_id":"D054537"}]},{"id":"4190","type":"Chemical","text":["carbamazepine"],"offsets":[[168,181]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"4191","type":"Chemical","text":["carbamazepine"],"offsets":[[313,326]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"4192","type":"Disease","text":["cardiac dysfunction"],"offsets":[[338,357]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"4193","type":"Disease","text":["sinus tachycardias"],"offsets":[[395,413]],"normalized":[{"db_name":"MESH","db_id":"D013616"}]},{"id":"4194","type":"Chemical","text":["carbamazepine"],"offsets":[[442,455]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"4195","type":"Disease","text":["overdose"],"offsets":[[456,464]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"4196","type":"Disease","text":["bradyarrhythmias"],"offsets":[[572,588]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"4197","type":"Disease","text":["atrioventricular conduction delay"],"offsets":[[592,625]],"normalized":[{"db_name":"MESH","db_id":"D054537"}]},{"id":"4198","type":"Chemical","text":["carbamazepine"],"offsets":[[683,696]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"4199","type":"Chemical","text":["carbamazepine"],"offsets":[[719,732]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"4200","type":"Disease","text":["psychiatric"],"offsets":[[788,799]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]}],"events":[],"coreferences":[],"relations":[{"id":"4201","type":"CID","arg1_id":"4186","arg2_id":"4189","normalized":[]},{"id":"4202","type":"CID","arg1_id":"4186","arg2_id":"4197","normalized":[]},{"id":"4203","type":"CID","arg1_id":"4190","arg2_id":"4189","normalized":[]},{"id":"4204","type":"CID","arg1_id":"4190","arg2_id":"4197","normalized":[]},{"id":"4205","type":"CID","arg1_id":"4191","arg2_id":"4189","normalized":[]},{"id":"4206","type":"CID","arg1_id":"4191","arg2_id":"4197","normalized":[]},{"id":"4207","type":"CID","arg1_id":"4194","arg2_id":"4189","normalized":[]},{"id":"4208","type":"CID","arg1_id":"4194","arg2_id":"4197","normalized":[]},{"id":"4209","type":"CID","arg1_id":"4198","arg2_id":"4189","normalized":[]},{"id":"4210","type":"CID","arg1_id":"4198","arg2_id":"4197","normalized":[]},{"id":"4211","type":"CID","arg1_id":"4199","arg2_id":"4189","normalized":[]},{"id":"4212","type":"CID","arg1_id":"4199","arg2_id":"4197","normalized":[]},{"id":"4213","type":"CID","arg1_id":"4186","arg2_id":"4188","normalized":[]},{"id":"4214","type":"CID","arg1_id":"4186","arg2_id":"4196","normalized":[]},{"id":"4215","type":"CID","arg1_id":"4190","arg2_id":"4188","normalized":[]},{"id":"4216","type":"CID","arg1_id":"4190","arg2_id":"4196","normalized":[]},{"id":"4217","type":"CID","arg1_id":"4191","arg2_id":"4188","normalized":[]},{"id":"4218","type":"CID","arg1_id":"4191","arg2_id":"4196","normalized":[]},{"id":"4219","type":"CID","arg1_id":"4194","arg2_id":"4188","normalized":[]},{"id":"4220","type":"CID","arg1_id":"4194","arg2_id":"4196","normalized":[]},{"id":"4221","type":"CID","arg1_id":"4198","arg2_id":"4188","normalized":[]},{"id":"4222","type":"CID","arg1_id":"4198","arg2_id":"4196","normalized":[]},{"id":"4223","type":"CID","arg1_id":"4199","arg2_id":"4188","normalized":[]},{"id":"4224","type":"CID","arg1_id":"4199","arg2_id":"4196","normalized":[]},{"id":"4225","type":"CID","arg1_id":"4186","arg2_id":"4193","normalized":[]},{"id":"4226","type":"CID","arg1_id":"4190","arg2_id":"4193","normalized":[]},{"id":"4227","type":"CID","arg1_id":"4191","arg2_id":"4193","normalized":[]},{"id":"4228","type":"CID","arg1_id":"4194","arg2_id":"4193","normalized":[]},{"id":"4229","type":"CID","arg1_id":"4198","arg2_id":"4193","normalized":[]},{"id":"4230","type":"CID","arg1_id":"4199","arg2_id":"4193","normalized":[]}]}
{"id":"4231","document_id":"20558148","passages":[{"id":"4232","type":"title","text":["Glutamatergic neurotransmission mediated by NMDA receptors in the inferior colliculus can modulate haloperidol-induced catalepsy."],"offsets":[[0,129]]},{"id":"4233","type":"abstract","text":["The inferior colliculus (IC) is primarily involved in the processing of auditory information, but it is distinguished from other auditory nuclei in the brainstem by its connections with structures of the motor system. Functional evidence relating the IC to motor behavior derives from experiments showing that activation of the IC by electrical stimulation or excitatory amino acid microinjection causes freezing, escape-like behavior, and immobility. However, the nature of this immobility is still unclear. The present study examined the influence of excitatory amino acid-mediated mechanisms in the IC on the catalepsy induced by the dopamine receptor blocker haloperidol administered systemically (1 or 0.5 mg\/kg) in rats. Haloperidol-induced catalepsy was challenged with prior intracollicular microinjections of glutamate NMDA receptor antagonists, MK-801 (15 or 30 mmol\/0.5 microl) and AP7 (10 or 20 nmol\/0.5 microl), or of the NMDA receptor agonist N-methyl-d-aspartate (NMDA, 20 or 30 nmol\/0.5 microl). The results showed that intracollicular microinjection of MK-801 and AP7 previous to systemic injections of haloperidol significantly attenuated the catalepsy, as indicated by a reduced latency to step down from a horizontal bar. Accordingly, intracollicular microinjection of NMDA increased the latency to step down the bar. These findings suggest that glutamate-mediated mechanisms in the neural circuits at the IC level influence haloperidol-induced catalepsy and participate in the regulation of motor activity."],"offsets":[[130,1657]]}],"entities":[{"id":"4234","type":"Chemical","text":["NMDA"],"offsets":[[44,48]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"4235","type":"Chemical","text":["haloperidol"],"offsets":[[99,110]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"4236","type":"Disease","text":["catalepsy"],"offsets":[[119,128]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"4237","type":"Chemical","text":["amino acid"],"offsets":[[501,511]],"normalized":[{"db_name":"MESH","db_id":"D000596"}]},{"id":"4238","type":"Chemical","text":["amino acid"],"offsets":[[694,704]],"normalized":[{"db_name":"MESH","db_id":"D000596"}]},{"id":"4239","type":"Disease","text":["catalepsy"],"offsets":[[742,751]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"4240","type":"Chemical","text":["dopamine"],"offsets":[[767,775]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"4241","type":"Chemical","text":["haloperidol"],"offsets":[[793,804]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"4242","type":"Chemical","text":["Haloperidol"],"offsets":[[857,868]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"4243","type":"Disease","text":["catalepsy"],"offsets":[[877,886]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"4244","type":"Chemical","text":["glutamate"],"offsets":[[948,957]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"4245","type":"Chemical","text":["NMDA"],"offsets":[[958,962]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"4246","type":"Chemical","text":["MK-801"],"offsets":[[985,991]],"normalized":[{"db_name":"MESH","db_id":"D016291"}]},{"id":"4247","type":"Chemical","text":["AP7"],"offsets":[[1023,1026]],"normalized":[{"db_name":"MESH","db_id":"C031231"}]},{"id":"4248","type":"Chemical","text":["NMDA"],"offsets":[[1065,1069]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"4249","type":"Chemical","text":["N-methyl-d-aspartate"],"offsets":[[1087,1107]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"4250","type":"Chemical","text":["NMDA"],"offsets":[[1109,1113]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"4251","type":"Chemical","text":["MK-801"],"offsets":[[1200,1206]],"normalized":[{"db_name":"MESH","db_id":"D016291"}]},{"id":"4252","type":"Chemical","text":["AP7"],"offsets":[[1211,1214]],"normalized":[{"db_name":"MESH","db_id":"C031231"}]},{"id":"4253","type":"Chemical","text":["haloperidol"],"offsets":[[1250,1261]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"4254","type":"Disease","text":["catalepsy"],"offsets":[[1291,1300]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"4255","type":"Chemical","text":["NMDA"],"offsets":[[1419,1423]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"4256","type":"Chemical","text":["glutamate"],"offsets":[[1496,1505]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"4257","type":"Chemical","text":["haloperidol"],"offsets":[[1575,1586]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"4258","type":"Disease","text":["catalepsy"],"offsets":[[1595,1604]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]}],"events":[],"coreferences":[],"relations":[{"id":"4259","type":"CID","arg1_id":"4235","arg2_id":"4236","normalized":[]},{"id":"4260","type":"CID","arg1_id":"4235","arg2_id":"4239","normalized":[]},{"id":"4261","type":"CID","arg1_id":"4235","arg2_id":"4243","normalized":[]},{"id":"4262","type":"CID","arg1_id":"4235","arg2_id":"4254","normalized":[]},{"id":"4263","type":"CID","arg1_id":"4235","arg2_id":"4258","normalized":[]},{"id":"4264","type":"CID","arg1_id":"4241","arg2_id":"4236","normalized":[]},{"id":"4265","type":"CID","arg1_id":"4241","arg2_id":"4239","normalized":[]},{"id":"4266","type":"CID","arg1_id":"4241","arg2_id":"4243","normalized":[]},{"id":"4267","type":"CID","arg1_id":"4241","arg2_id":"4254","normalized":[]},{"id":"4268","type":"CID","arg1_id":"4241","arg2_id":"4258","normalized":[]},{"id":"4269","type":"CID","arg1_id":"4242","arg2_id":"4236","normalized":[]},{"id":"4270","type":"CID","arg1_id":"4242","arg2_id":"4239","normalized":[]},{"id":"4271","type":"CID","arg1_id":"4242","arg2_id":"4243","normalized":[]},{"id":"4272","type":"CID","arg1_id":"4242","arg2_id":"4254","normalized":[]},{"id":"4273","type":"CID","arg1_id":"4242","arg2_id":"4258","normalized":[]},{"id":"4274","type":"CID","arg1_id":"4253","arg2_id":"4236","normalized":[]},{"id":"4275","type":"CID","arg1_id":"4253","arg2_id":"4239","normalized":[]},{"id":"4276","type":"CID","arg1_id":"4253","arg2_id":"4243","normalized":[]},{"id":"4277","type":"CID","arg1_id":"4253","arg2_id":"4254","normalized":[]},{"id":"4278","type":"CID","arg1_id":"4253","arg2_id":"4258","normalized":[]},{"id":"4279","type":"CID","arg1_id":"4257","arg2_id":"4236","normalized":[]},{"id":"4280","type":"CID","arg1_id":"4257","arg2_id":"4239","normalized":[]},{"id":"4281","type":"CID","arg1_id":"4257","arg2_id":"4243","normalized":[]},{"id":"4282","type":"CID","arg1_id":"4257","arg2_id":"4254","normalized":[]},{"id":"4283","type":"CID","arg1_id":"4257","arg2_id":"4258","normalized":[]}]}
{"id":"4284","document_id":"19940105","passages":[{"id":"4285","type":"title","text":["Metabotropic glutamate 7 receptor subtype modulates motor symptoms in rodent models of Parkinson's disease."],"offsets":[[0,107]]},{"id":"4286","type":"abstract","text":["Metabotropic glutamate (mGlu) receptors modulate synaptic transmission in the central nervous system and represent promising therapeutic targets for symptomatic treatment of Parkinson's disease (PD). Among the eight mGlu receptor subtypes, mGlu7 receptor is prominently expressed in the basal ganglia, but its role in restoring motor function in animal models of PD is not known. The effects of N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN082), the first selective allosteric activator of mGlu7 receptors, were thus tested in different rodent models of PD. Here, we show that oral (5 mg\/kg) or intrastriatal administration (0.1 and 0.5 nmol) of AMN082 reverses haloperidol-induced catalepsy in rats. AMN082 (2.5 and 5 mg\/kg) reduces apomorphine-induced rotations in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats. In a more complex task commonly used to evaluate major akinetic symptoms of PD patients, 5 mg\/kg AMN082 reverses the increased reaction time to respond to a cue of bilateral 6-OHDA-lesioned rats. In addition, AMN082 reduces the duration of haloperidol-induced catalepsy in a mGlu7 receptor-dependent manner in wild-type but not mGlu7 receptor knockout mice. Higher doses of AMN082 (10 and 20 mg\/kg p.o.) have no effect on the same models of PD. Overall these findings suggest that mGlu7 receptor activation can reverse motor dysfunction associated with reduced dopamine activity. Selective ligands of mGlu7 receptor subtypes may thus be considered as promising compounds for the development of antiparkinsonian therapeutic strategies."],"offsets":[[108,1673]]}],"entities":[{"id":"4287","type":"Chemical","text":["glutamate"],"offsets":[[13,22]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"4288","type":"Disease","text":["Parkinson's disease"],"offsets":[[87,106]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"4289","type":"Chemical","text":["glutamate"],"offsets":[[121,130]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"4290","type":"Disease","text":["Parkinson's disease"],"offsets":[[282,301]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"4291","type":"Disease","text":["PD"],"offsets":[[303,305]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"4292","type":"Disease","text":["PD"],"offsets":[[471,473]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"4293","type":"Chemical","text":["N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride"],"offsets":[[503,554]],"normalized":[{"db_name":"MESH","db_id":"C507346"}]},{"id":"4294","type":"Chemical","text":["AMN082"],"offsets":[[556,562]],"normalized":[{"db_name":"MESH","db_id":"C507346"}]},{"id":"4295","type":"Disease","text":["PD"],"offsets":[[673,675]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"4296","type":"Chemical","text":["AMN082"],"offsets":[[765,771]],"normalized":[{"db_name":"MESH","db_id":"C507346"}]},{"id":"4297","type":"Chemical","text":["haloperidol"],"offsets":[[781,792]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"4298","type":"Disease","text":["catalepsy"],"offsets":[[801,810]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"4299","type":"Chemical","text":["AMN082"],"offsets":[[820,826]],"normalized":[{"db_name":"MESH","db_id":"C507346"}]},{"id":"4300","type":"Chemical","text":["apomorphine"],"offsets":[[853,864]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"4301","type":"Chemical","text":["6-hydroxydopamine"],"offsets":[[897,914]],"normalized":[{"db_name":"MESH","db_id":"D016627"}]},{"id":"4302","type":"Chemical","text":["6-OHDA"],"offsets":[[916,922]],"normalized":[{"db_name":"MESH","db_id":"D016627"}]},{"id":"4303","type":"Disease","text":["akinetic"],"offsets":[[994,1002]],"normalized":[{"db_name":"MESH","db_id":"D018476"}]},{"id":"4304","type":"Disease","text":["PD"],"offsets":[[1015,1017]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"4305","type":"Chemical","text":["AMN082"],"offsets":[[1036,1042]],"normalized":[{"db_name":"MESH","db_id":"C507346"}]},{"id":"4306","type":"Chemical","text":["6-OHDA"],"offsets":[[1113,1119]],"normalized":[{"db_name":"MESH","db_id":"D016627"}]},{"id":"4307","type":"Chemical","text":["AMN082"],"offsets":[[1148,1154]],"normalized":[{"db_name":"MESH","db_id":"C507346"}]},{"id":"4308","type":"Chemical","text":["haloperidol"],"offsets":[[1179,1190]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"4309","type":"Disease","text":["catalepsy"],"offsets":[[1199,1208]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"4310","type":"Chemical","text":["AMN082"],"offsets":[[1313,1319]],"normalized":[{"db_name":"MESH","db_id":"C507346"}]},{"id":"4311","type":"Disease","text":["PD"],"offsets":[[1380,1382]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"4312","type":"Chemical","text":["dopamine"],"offsets":[[1500,1508]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]}],"events":[],"coreferences":[],"relations":[{"id":"4313","type":"CID","arg1_id":"4297","arg2_id":"4298","normalized":[]},{"id":"4314","type":"CID","arg1_id":"4297","arg2_id":"4309","normalized":[]},{"id":"4315","type":"CID","arg1_id":"4308","arg2_id":"4298","normalized":[]},{"id":"4316","type":"CID","arg1_id":"4308","arg2_id":"4309","normalized":[]}]}
{"id":"4317","document_id":"19923525","passages":[{"id":"4318","type":"title","text":["Nimodipine prevents memory impairment caused by nitroglycerin-induced hypotension in adult mice."],"offsets":[[0,96]]},{"id":"4319","type":"abstract","text":["BACKGROUND: Hypotension and a resultant decrease in cerebral blood flow have been implicated in the development of cognitive dysfunction. We tested the hypothesis that nimodipine (NIMO) administered at the onset of nitroglycerin (NTG)-induced hypotension would preserve long-term associative memory. METHODS: The passive avoidance (PA) paradigm was used to assess memory retention. For PA training, latencies (seconds) were recorded for entry from a suspended platform into a Plexiglas tube where a shock was automatically delivered. Latencies were recorded 48 h later for a testing trial. Ninety-six Swiss-Webster mice (30-35 g, 6-8 wk), were randomized into 6 groups 1) saline (control), 2) NTG immediately after learning, 3) NTG 3 h after learning, 4) NTG and NIMO, 5) vehicle, and 6) NIMO alone. The extent of hypotension and changes in brain tissue oxygenation (PbtO(2)) and in cerebral blood flow were studied in a separate group of animals. RESULTS: All groups exhibited similar training latencies (17.0 +\/- 4.6 s). Mice subjected to hypotensive episodes showed a significant decrease in latency time (178 +\/- 156 s) compared with those injected with saline, NTG + NIMO, or delayed NTG (580 +\/- 81 s, 557 +\/- 67 s, and 493 +\/- 146 s, respectively). A Kruskal-Wallis 1-way analysis of variance indicated a significant difference among the 4 treatment groups (H = 15.34; P < 0.001). In a separate group of mice not subjected to behavioral studies, the same dose of NTG (n = 3) and NTG + NIMO (n = 3) caused mean arterial blood pressure to decrease from 85.9 +\/- 3.8 mm Hg sem to 31.6 +\/- 0.8 mm Hg sem and from 86.2 +\/- 3.7 mm Hg sem to 32.6 +\/- 0.2 mm Hg sem, respectively. Mean arterial blood pressure in mice treated with NIMO alone decreased from 88.1 +\/- 3.8 mm Hg to 80.0 +\/- 2.9 mm Hg. The intergroup difference was statistically significant (P < 0.05). PbtO(2) decreased from 51.7 +\/- 4.5 mm Hg sem to 33.8 +\/- 5.2 mm Hg sem in the NTG group and from 38.6 +\/- 6.1 mm Hg sem to 25.4 +\/- 2.0 mm Hg sem in the NTG + NIMO groups, respectively. There were no significant differences among groups. CONCLUSION: In a PA retention paradigm, the injection of NTG immediately after learning produced a significant impairment of long-term associative memory in mice, whereas delayed induced hypotension had no effect. NIMO attenuated the disruption in consolidation of long-term memory caused by NTG but did not improve latency in the absence of hypotension. The observed effect of NIMO may have been attributable to the preservation of calcium homeostasis during hypotension, because there were no differences in the PbtO(2) indices among groups."],"offsets":[[97,2745]]}],"entities":[{"id":"4320","type":"Chemical","text":["Nimodipine"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D009553"}]},{"id":"4321","type":"Disease","text":["memory impairment"],"offsets":[[20,37]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"4322","type":"Chemical","text":["nitroglycerin"],"offsets":[[48,61]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"4323","type":"Disease","text":["hypotension"],"offsets":[[70,81]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"4324","type":"Disease","text":["Hypotension"],"offsets":[[109,120]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"4325","type":"Disease","text":["cognitive 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{"id":"4482","document_id":"19058474","passages":[{"id":"4483","type":"title","text":["Fatal haemopericardium and gastrointestinal haemorrhage due to possible interaction of cranberry juice with warfarin."],"offsets":[[0,117]]},{"id":"4484","type":"abstract","text":["We report a case of fatal internal haemorrhage in an elderly man who consumed only cranberry juice for two weeks while maintaining his usual dosage of warfarin. We propose that naturally occurring compounds such as flavonoids, which are present in fruit juices, may increase the potency of warfarin by competing for the enzymes that normally inactivate warfarin. While traditionally regarded as foodstuffs, consumption of fruit juices should be considered when patients develop adverse drug reactions."],"offsets":[[118,619]]}],"entities":[{"id":"4485","type":"Disease","text":["haemopericardium"],"offsets":[[6,22]],"normalized":[{"db_name":"MESH","db_id":"D010490"}]},{"id":"4486","type":"Disease","text":["gastrointestinal haemorrhage"],"offsets":[[27,55]],"normalized":[{"db_name":"MESH","db_id":"D006471"}]},{"id":"4487","type":"Chemical","text":["warfarin"],"offsets":[[108,116]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"4488","type":"Disease","text":["haemorrhage"],"offsets":[[153,164]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"4489","type":"Chemical","text":["warfarin"],"offsets":[[269,277]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"4490","type":"Chemical","text":["flavonoids"],"offsets":[[333,343]],"normalized":[{"db_name":"MESH","db_id":"D005419"}]},{"id":"4491","type":"Chemical","text":["warfarin"],"offsets":[[408,416]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"4492","type":"Chemical","text":["warfarin"],"offsets":[[471,479]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]}],"events":[],"coreferences":[],"relations":[{"id":"4493","type":"CID","arg1_id":"4490","arg2_id":"4486","normalized":[]},{"id":"4494","type":"CID","arg1_id":"4487","arg2_id":"4486","normalized":[]},{"id":"4495","type":"CID","arg1_id":"4489","arg2_id":"4486","normalized":[]},{"id":"4496","type":"CID","arg1_id":"4491","arg2_id":"4486","normalized":[]},{"id":"4497","type":"CID","arg1_id":"4492","arg2_id":"4486","normalized":[]}]}
{"id":"4498","document_id":"18808529","passages":[{"id":"4499","type":"title","text":["Isoproterenol induces primary loss of dystrophin in rat hearts: correlation with myocardial injury."],"offsets":[[0,99]]},{"id":"4500","type":"abstract","text":["The mechanism of isoproterenol-induced myocardial damage is unknown, but a mismatch of oxygen supply vs. demand following coronary hypotension and myocardial hyperactivity is the best explanation for the complex morphological alterations observed. Severe alterations in the structural integrity of the sarcolemma of cardiomyocytes have been demonstrated to be caused by isoproterenol. Taking into account that the sarcolemmal integrity is stabilized by the dystrophin-glycoprotein complex (DGC) that connects actin and laminin in contractile machinery and extracellular matrix and by integrins, this study tests the hypothesis that isoproterenol affects sarcolemmal stability through changes in the DGC and integrins. We found different sensitivity of the DGC and integrin to isoproterenol subcutaneous administration. Immunofluorescent staining revealed that dystrophin is the most sensitive among the structures connecting the actin in the cardiomyocyte cytoskeleton and the extracellular matrix. The sarcomeric actin dissolution occurred after the reduction or loss of dystrophin. Subsequently, after lysis of myofilaments, gamma-sarcoglycan, beta-dystroglycan, beta1-integrin, and laminin alpha-2 expressions were reduced followed by their breakdown, as epiphenomena of the myocytolytic process. In conclusion, administration of isoproterenol to rats results in primary loss of dystrophin, the most sensitive among the structural proteins that form the DGC that connects the extracellular matrix and the cytoskeleton in cardiomyocyte. These changes, related to ischaemic injury, explain the severe alterations in the structural integrity of the sarcolemma of cardiomyocytes and hence severe and irreversible injury induced by isoproterenol."],"offsets":[[100,1844]]}],"entities":[{"id":"4501","type":"Chemical","text":["Isoproterenol"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"4502","type":"Disease","text":["myocardial injury"],"offsets":[[81,98]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"4503","type":"Chemical","text":["isoproterenol"],"offsets":[[117,130]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"4504","type":"Disease","text":["myocardial damage"],"offsets":[[139,156]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"4505","type":"Chemical","text":["oxygen"],"offsets":[[187,193]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"4506","type":"Disease","text":["hypotension"],"offsets":[[231,242]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"4507","type":"Disease","text":["myocardial hyperactivity"],"offsets":[[247,271]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"4508","type":"Chemical","text":["isoproterenol"],"offsets":[[470,483]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"4509","type":"Chemical","text":["isoproterenol"],"offsets":[[732,745]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"4510","type":"Chemical","text":["isoproterenol"],"offsets":[[876,889]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"4511","type":"Chemical","text":["isoproterenol"],"offsets":[[1433,1446]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"4512","type":"Disease","text":["ischaemic injury"],"offsets":[[1665,1681]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"4513","type":"Chemical","text":["isoproterenol"],"offsets":[[1830,1843]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]}],"events":[],"coreferences":[],"relations":[{"id":"4514","type":"CID","arg1_id":"4501","arg2_id":"4502","normalized":[]},{"id":"4515","type":"CID","arg1_id":"4501","arg2_id":"4504","normalized":[]},{"id":"4516","type":"CID","arg1_id":"4501","arg2_id":"4507","normalized":[]},{"id":"4517","type":"CID","arg1_id":"4503","arg2_id":"4502","normalized":[]},{"id":"4518","type":"CID","arg1_id":"4503","arg2_id":"4504","normalized":[]},{"id":"4519","type":"CID","arg1_id":"4503","arg2_id":"4507","normalized":[]},{"id":"4520","type":"CID","arg1_id":"4508","arg2_id":"4502","normalized":[]},{"id":"4521","type":"CID","arg1_id":"4508","arg2_id":"4504","normalized":[]},{"id":"4522","type":"CID","arg1_id":"4508","arg2_id":"4507","normalized":[]},{"id":"4523","type":"CID","arg1_id":"4509","arg2_id":"4502","normalized":[]},{"id":"4524","type":"CID","arg1_id":"4509","arg2_id":"4504","normalized":[]},{"id":"4525","type":"CID","arg1_id":"4509","arg2_id":"4507","normalized":[]},{"id":"4526","type":"CID","arg1_id":"4510","arg2_id":"4502","normalized":[]},{"id":"4527","type":"CID","arg1_id":"4510","arg2_id":"4504","normalized":[]},{"id":"4528","type":"CID","arg1_id":"4510","arg2_id":"4507","normalized":[]},{"id":"4529","type":"CID","arg1_id":"4511","arg2_id":"4502","normalized":[]},{"id":"4530","type":"CID","arg1_id":"4511","arg2_id":"4504","normalized":[]},{"id":"4531","type":"CID","arg1_id":"4511","arg2_id":"4507","normalized":[]},{"id":"4532","type":"CID","arg1_id":"4513","arg2_id":"4502","normalized":[]},{"id":"4533","type":"CID","arg1_id":"4513","arg2_id":"4504","normalized":[]},{"id":"4534","type":"CID","arg1_id":"4513","arg2_id":"4507","normalized":[]},{"id":"4535","type":"CID","arg1_id":"4501","arg2_id":"4512","normalized":[]},{"id":"4536","type":"CID","arg1_id":"4503","arg2_id":"4512","normalized":[]},{"id":"4537","type":"CID","arg1_id":"4508","arg2_id":"4512","normalized":[]},{"id":"4538","type":"CID","arg1_id":"4509","arg2_id":"4512","normalized":[]},{"id":"4539","type":"CID","arg1_id":"4510","arg2_id":"4512","normalized":[]},{"id":"4540","type":"CID","arg1_id":"4511","arg2_id":"4512","normalized":[]},{"id":"4541","type":"CID","arg1_id":"4513","arg2_id":"4512","normalized":[]}]}
{"id":"4542","document_id":"18674790","passages":[{"id":"4543","type":"title","text":["High fat diet-fed obese rats are highly sensitive to doxorubicin-induced cardiotoxicity."],"offsets":[[0,88]]},{"id":"4544","type":"abstract","text":["Often, chemotherapy by doxorubicin (Adriamycin) is limited due to life threatening cardiotoxicity in patients during and posttherapy. Recently, we have shown that moderate diet restriction remarkably protects against doxorubicin-induced cardiotoxicity. This cardioprotection is accompanied by decreased cardiac oxidative stress and triglycerides and increased cardiac fatty-acid oxidation, ATP synthesis, and upregulated JAK\/STAT3 pathway. In the current study, we investigated whether a physiological intervention by feeding 40% high fat diet (HFD), which induces obesity in male Sprague-Dawley rats (250-275 g), sensitizes to doxorubicin-induced cardiotoxicity. A LD(10) dose (8 mg doxorubicin\/kg, ip) administered on day 43 of the HFD feeding regimen led to higher cardiotoxicity, cardiac dysfunction, lipid peroxidation, and 80% mortality in the obese (OB) rats in the absence of any significant renal or hepatic toxicity. Doxorubicin toxicokinetics studies revealed no change in accumulation of doxorubicin and doxorubicinol (toxic metabolite) in the normal diet-fed (ND) and OB hearts. Mechanistic studies revealed that OB rats are sensitized due to: (1) higher oxyradical stress leading to upregulation of uncoupling proteins 2 and 3, (2) downregulation of cardiac peroxisome proliferators activated receptor-alpha, (3) decreased plasma adiponectin levels, (4) decreased cardiac fatty-acid oxidation (666.9+\/-14.0 nmol\/min\/g heart in ND versus 400.2+\/-11.8 nmol\/min\/g heart in OB), (5) decreased mitochondrial AMP-alpha2 protein kinase, and (6) 86% drop in cardiac ATP levels accompanied by decreased ATP\/ADP ratio after doxorubicin administration. Decreased cardiac erythropoietin and increased SOCS3 further downregulated the cardioprotective JAK\/STAT3 pathway. In conclusion, HFD-induced obese rats are highly sensitized to doxorubicin-induced cardiotoxicity by substantially downregulating cardiac mitochondrial ATP generation, increasing oxidative stress and downregulating the JAK\/STAT3 pathway."],"offsets":[[89,2097]]}],"entities":[{"id":"4545","type":"Chemical","text":["fat"],"offsets":[[5,8]],"normalized":[{"db_name":"MESH","db_id":"D004041"}]},{"id":"4546","type":"Disease","text":["obese"],"offsets":[[18,23]],"normalized":[{"db_name":"MESH","db_id":"D009765"}]},{"id":"4547","type":"Chemical","text":["doxorubicin"],"offsets":[[53,64]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"4548","type":"Disease","text":["cardiotoxicity"],"offsets":[[73,87]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"4549","type":"Chemical","text":["doxorubicin"],"offsets":[[112,123]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"4550","type":"Chemical","text":["Adriamycin"],"offsets":[[125,135]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"4551","type":"Disease","text":["cardiotoxicity"],"offsets":[[172,186]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"4552","type":"Chemical","text":["doxorubicin"],"offsets":[[306,317]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"4553","type":"Disease","text":["cardiotoxicity"],"offsets":[[326,340]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"4554","type":"Chemical","text":["triglycerides"],"offsets":[[421,434]],"normalized":[{"db_name":"MESH","db_id":"D014280"}]},{"id":"4555","type":"Chemical","text":["ATP"],"offsets":[[479,482]],"normalized":[{"db_name":"MESH","db_id":"D000255"}]},{"id":"4556","type":"Chemical","text":["fat"],"offsets":[[624,627]],"normalized":[{"db_name":"MESH","db_id":"D004041"}]},{"id":"4557","type":"Disease","text":["obesity"],"offsets":[[654,661]],"normalized":[{"db_name":"MESH","db_id":"D009765"}]},{"id":"4558","type":"Chemical","text":["doxorubicin"],"offsets":[[717,728]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"4559","type":"Disease","text":["cardiotoxicity"],"offsets":[[737,751]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"4560","type":"Chemical","text":["doxorubicin"],"offsets":[[773,784]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"4561","type":"Disease","text":["cardiotoxicity"],"offsets":[[857,871]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"4562","type":"Disease","text":["cardiac dysfunction"],"offsets":[[873,892]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"4563","type":"Disease","text":["obese"],"offsets":[[939,944]],"normalized":[{"db_name":"MESH","db_id":"D009765"}]},{"id":"4564","type":"Disease","text":["OB"],"offsets":[[946,948]],"normalized":[{"db_name":"MESH","db_id":"D009765"}]},{"id":"4565","type":"Disease","text":["renal or hepatic toxicity"],"offsets":[[989,1014]],"normalized":[{"db_name":"MESH","db_id":"D007674"},{"db_name":"MESH","db_id":"D056486"}]},{"id":"4566","type":"Disease","text":["renal","toxicity"],"offsets":[[989,994],[1006,1014]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"4567","type":"Disease","text":["hepatic toxicity"],"offsets":[[998,1014]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"4568","type":"Chemical","text":["Doxorubicin"],"offsets":[[1016,1027]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"4569","type":"Chemical","text":["doxorubicin"],"offsets":[[1089,1100]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"4570","type":"Chemical","text":["doxorubicinol"],"offsets":[[1105,1118]],"normalized":[{"db_name":"MESH","db_id":"C010013"}]},{"id":"4571","type":"Disease","text":["OB"],"offsets":[[1170,1172]],"normalized":[{"db_name":"MESH","db_id":"D009765"}]},{"id":"4572","type":"Disease","text":["OB"],"offsets":[[1215,1217]],"normalized":[{"db_name":"MESH","db_id":"D009765"}]},{"id":"4573","type":"Disease","text":["OB"],"offsets":[[1573,1575]],"normalized":[{"db_name":"MESH","db_id":"D009765"}]},{"id":"4574","type":"Chemical","text":["AMP"],"offsets":[[1606,1609]],"normalized":[{"db_name":"MESH","db_id":"D000249"}]},{"id":"4575","type":"Chemical","text":["ATP"],"offsets":[[1661,1664]],"normalized":[{"db_name":"MESH","db_id":"D000255"}]},{"id":"4576","type":"Chemical","text":["ATP"],"offsets":[[1697,1700]],"normalized":[{"db_name":"MESH","db_id":"D000255"}]},{"id":"4577","type":"Chemical","text":["ADP"],"offsets":[[1701,1704]],"normalized":[{"db_name":"MESH","db_id":"D000244"}]},{"id":"4578","type":"Chemical","text":["doxorubicin"],"offsets":[[1717,1728]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"4579","type":"Disease","text":["obese"],"offsets":[[1887,1892]],"normalized":[{"db_name":"MESH","db_id":"D009765"}]},{"id":"4580","type":"Chemical","text":["doxorubicin"],"offsets":[[1923,1934]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"4581","type":"Disease","text":["cardiotoxicity"],"offsets":[[1943,1957]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"4582","type":"Chemical","text":["ATP"],"offsets":[[2012,2015]],"normalized":[{"db_name":"MESH","db_id":"D000255"}]}],"events":[],"coreferences":[],"relations":[{"id":"4583","type":"CID","arg1_id":"4545","arg2_id":"4546","normalized":[]},{"id":"4584","type":"CID","arg1_id":"4545","arg2_id":"4557","normalized":[]},{"id":"4585","type":"CID","arg1_id":"4545","arg2_id":"4563","normalized":[]},{"id":"4586","type":"CID","arg1_id":"4545","arg2_id":"4564","normalized":[]},{"id":"4587","type":"CID","arg1_id":"4545","arg2_id":"4571","normalized":[]},{"id":"4588","type":"CID","arg1_id":"4545","arg2_id":"4572","normalized":[]},{"id":"4589","type":"CID","arg1_id":"4545","arg2_id":"4573","normalized":[]},{"id":"4590","type":"CID","arg1_id":"4545","arg2_id":"4579","normalized":[]},{"id":"4591","type":"CID","arg1_id":"4556","arg2_id":"4546","normalized":[]},{"id":"4592","type":"CID","arg1_id":"4556","arg2_id":"4557","normalized":[]},{"id":"4593","type":"CID","arg1_id":"4556","arg2_id":"4563","normalized":[]},{"id":"4594","type":"CID","arg1_id":"4556","arg2_id":"4564","normalized":[]},{"id":"4595","type":"CID","arg1_id":"4556","arg2_id":"4571","normalized":[]},{"id":"4596","type":"CID","arg1_id":"4556","arg2_id":"4572","normalized":[]},{"id":"4597","type":"CID","arg1_id":"4556","arg2_id":"4573","normalized":[]},{"id":"4598","type":"CID","arg1_id":"4556","arg2_id":"4579","normalized":[]},{"id":"4599","type":"CID","arg1_id":"4547","arg2_id":"4562","normalized":[]},{"id":"4600","type":"CID","arg1_id":"4549","arg2_id":"4562","normalized":[]},{"id":"4601","type":"CID","arg1_id":"4550","arg2_id":"4562","normalized":[]},{"id":"4602","type":"CID","arg1_id":"4552","arg2_id":"4562","normalized":[]},{"id":"4603","type":"CID","arg1_id":"4558","arg2_id":"4562","normalized":[]},{"id":"4604","type":"CID","arg1_id":"4560","arg2_id":"4562","normalized":[]},{"id":"4605","type":"CID","arg1_id":"4568","arg2_id":"4562","normalized":[]},{"id":"4606","type":"CID","arg1_id":"4569","arg2_id":"4562","normalized":[]},{"id":"4607","type":"CID","arg1_id":"4578","arg2_id":"4562","normalized":[]},{"id":"4608","type":"CID","arg1_id":"4580","arg2_id":"4562","normalized":[]}]}
{"id":"4609","document_id":"18441470","passages":[{"id":"4610","type":"title","text":["Complete atrioventricular block secondary to lithium therapy."],"offsets":[[0,61]]},{"id":"4611","type":"abstract","text":["Sinus node dysfunction has been reported most frequently among the adverse cardiovascular effects of lithium. In the present case, complete atrioventricular (AV) block with syncopal attacks developed secondary to lithium therapy, necessitating permanent pacemaker implantation. Serum lithium levels remained under or within the therapeutic range during the syncopal attacks. Lithium should be used with extreme caution, especially in patients with mild disturbance of AV conduction."],"offsets":[[62,544]]}],"entities":[{"id":"4612","type":"Disease","text":["atrioventricular block"],"offsets":[[9,31]],"normalized":[{"db_name":"MESH","db_id":"D054537"}]},{"id":"4613","type":"Chemical","text":["lithium"],"offsets":[[45,52]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"4614","type":"Disease","text":["Sinus node dysfunction"],"offsets":[[62,84]],"normalized":[{"db_name":"MESH","db_id":"D012804"}]},{"id":"4615","type":"Chemical","text":["lithium"],"offsets":[[163,170]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"4616","type":"Disease","text":["atrioventricular (AV) block"],"offsets":[[202,229]],"normalized":[{"db_name":"MESH","db_id":"D054537"}]},{"id":"4617","type":"Disease","text":["syncopal attacks"],"offsets":[[235,251]],"normalized":[{"db_name":"MESH","db_id":"D013575"}]},{"id":"4618","type":"Chemical","text":["lithium"],"offsets":[[275,282]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"4619","type":"Chemical","text":["lithium"],"offsets":[[346,353]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"4620","type":"Disease","text":["syncopal attacks"],"offsets":[[419,435]],"normalized":[{"db_name":"MESH","db_id":"D013575"}]},{"id":"4621","type":"Chemical","text":["Lithium"],"offsets":[[437,444]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]}],"events":[],"coreferences":[],"relations":[{"id":"4622","type":"CID","arg1_id":"4613","arg2_id":"4614","normalized":[]},{"id":"4623","type":"CID","arg1_id":"4615","arg2_id":"4614","normalized":[]},{"id":"4624","type":"CID","arg1_id":"4618","arg2_id":"4614","normalized":[]},{"id":"4625","type":"CID","arg1_id":"4619","arg2_id":"4614","normalized":[]},{"id":"4626","type":"CID","arg1_id":"4621","arg2_id":"4614","normalized":[]},{"id":"4627","type":"CID","arg1_id":"4613","arg2_id":"4612","normalized":[]},{"id":"4628","type":"CID","arg1_id":"4613","arg2_id":"4616","normalized":[]},{"id":"4629","type":"CID","arg1_id":"4615","arg2_id":"4612","normalized":[]},{"id":"4630","type":"CID","arg1_id":"4615","arg2_id":"4616","normalized":[]},{"id":"4631","type":"CID","arg1_id":"4618","arg2_id":"4612","normalized":[]},{"id":"4632","type":"CID","arg1_id":"4618","arg2_id":"4616","normalized":[]},{"id":"4633","type":"CID","arg1_id":"4619","arg2_id":"4612","normalized":[]},{"id":"4634","type":"CID","arg1_id":"4619","arg2_id":"4616","normalized":[]},{"id":"4635","type":"CID","arg1_id":"4621","arg2_id":"4612","normalized":[]},{"id":"4636","type":"CID","arg1_id":"4621","arg2_id":"4616","normalized":[]}]}
{"id":"4637","document_id":"17366349","passages":[{"id":"4638","type":"title","text":["Neuroleptic malignant syndrome induced by ziprasidone on the second day of treatment."],"offsets":[[0,85]]},{"id":"4639","type":"abstract","text":["Neuroleptic malignant syndrome (NMS) is the rarest and most serious of the neuroleptic-induced movement disorders. We describe a case of neuroleptic malignant syndrome (NMS) associated with the use of ziprasidone. Although conventional neuroleptics are more frequently associated with NMS, atypical antipsychotic drugs like ziprasidone may also be a cause. The patient is a 24-year-old male with a history of schizophrenia who developed signs and symptoms of NMS after 2 days of treatment with an 80-mg\/day dose of orally administrated ziprasidone. This case is the earliest (second day of treatment) NMS due to ziprasidone reported in the literature."],"offsets":[[86,737]]}],"entities":[{"id":"4640","type":"Disease","text":["Neuroleptic malignant syndrome"],"offsets":[[0,30]],"normalized":[{"db_name":"MESH","db_id":"D009459"}]},{"id":"4641","type":"Chemical","text":["ziprasidone"],"offsets":[[42,53]],"normalized":[{"db_name":"MESH","db_id":"C092292"}]},{"id":"4642","type":"Disease","text":["Neuroleptic malignant syndrome"],"offsets":[[86,116]],"normalized":[{"db_name":"MESH","db_id":"D009459"}]},{"id":"4643","type":"Disease","text":["NMS"],"offsets":[[118,121]],"normalized":[{"db_name":"MESH","db_id":"D009459"}]},{"id":"4644","type":"Disease","text":["movement disorders"],"offsets":[[181,199]],"normalized":[{"db_name":"MESH","db_id":"D009069"}]},{"id":"4645","type":"Disease","text":["neuroleptic malignant 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{"id":"4695","document_id":"16584858","passages":[{"id":"4696","type":"title","text":["Role of mangiferin on biochemical alterations and antioxidant status in isoproterenol-induced myocardial infarction in rats."],"offsets":[[0,124]]},{"id":"4697","type":"abstract","text":["The current study dealt with the protective role of mangiferin, a polyphenol from Mangifera indica Linn. (Anacardiaceae), on isoproterenol (ISPH)-induced myocardial infarction (MI) in rats through its antioxidative mechanism. Subcutaneous injection of ISPH (200 mg\/kg body weight in 1 ml saline) to rats for 2 consecutive days caused myocardial damage in rat heart, which was determined by the increased activity of serum lactate dehydrogenase (LDH) and creatine phosphokinase isoenzymes (CK-MB), increased uric acid level and reduced plasma iron binding capacity. The protective role of mangiferin was analyzed by triphenyl tetrazolium chloride (TTC) test used for macroscopic enzyme mapping assay of the ischemic myocardium. The heart tissue antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione transferase and glutathione reductase activities, non-enzymic antioxidants such as cerruloplasmin, Vitamin C, Vitamin E and glutathione levels were altered in MI rats. Upon pretreatment with mangiferin (100 mg\/kg body weight suspended in 2 ml of dimethyl sulphoxide) given intraperitoneally for 28 days to MI rats protected the above-mentioned parameters to fall from the normal levels. Activities of heart tissue enzymic antioxidants and serum non-enzymic antioxidants levels rose significantly upon mangiferin administration as compared to ISPH-induced MI rats. From the present study it is concluded that mangiferin exerts a beneficial effect against ISPH-induced MI due to its antioxidant potential, which regulated the tissues defense system against cardiac damage."],"offsets":[[125,1735]]}],"entities":[{"id":"4698","type":"Chemical","text":["mangiferin"],"offsets":[[8,18]],"normalized":[{"db_name":"MESH","db_id":"C013592"}]},{"id":"4699","type":"Chemical","text":["isoproterenol"],"offsets":[[72,85]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"4700","type":"Disease","text":["myocardial infarction"],"offsets":[[94,115]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"4701","type":"Chemical","text":["mangiferin"],"offsets":[[177,187]],"normalized":[{"db_name":"MESH","db_id":"C013592"}]},{"id":"4702","type":"Chemical","text":["polyphenol"],"offsets":[[191,201]],"normalized":[{"db_name":"MESH","db_id":"D059808"}]},{"id":"4703","type":"Chemical","text":["isoproterenol"],"offsets":[[250,263]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"4704","type":"Chemical","text":["ISPH"],"offsets":[[265,269]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"4705","type":"Disease","text":["myocardial infarction"],"offsets":[[279,300]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"4706","type":"Disease","text":["MI"],"offsets":[[302,304]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"4707","type":"Chemical","text":["ISPH"],"offsets":[[377,381]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"4708","type":"Disease","text":["myocardial damage"],"offsets":[[459,476]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"4709","type":"Chemical","text":["lactate"],"offsets":[[547,554]],"normalized":[{"db_name":"MESH","db_id":"D019344"}]},{"id":"4710","type":"Chemical","text":["creatine"],"offsets":[[579,587]],"normalized":[{"db_name":"MESH","db_id":"D003401"}]},{"id":"4711","type":"Chemical","text":["uric acid"],"offsets":[[632,641]],"normalized":[{"db_name":"MESH","db_id":"D014527"}]},{"id":"4712","type":"Chemical","text":["iron"],"offsets":[[667,671]],"normalized":[{"db_name":"MESH","db_id":"D007501"}]},{"id":"4713","type":"Chemical","text":["mangiferin"],"offsets":[[713,723]],"normalized":[{"db_name":"MESH","db_id":"C013592"}]},{"id":"4714","type":"Chemical","text":["triphenyl tetrazolium chloride"],"offsets":[[740,770]],"normalized":[{"db_name":"MESH","db_id":"C009591"}]},{"id":"4715","type":"Chemical","text":["TTC"],"offsets":[[772,775]],"normalized":[{"db_name":"MESH","db_id":"C009591"}]},{"id":"4716","type":"Disease","text":["ischemic myocardium"],"offsets":[[831,850]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"4717","type":"Chemical","text":["superoxide"],"offsets":[[897,907]],"normalized":[{"db_name":"MESH","db_id":"D013481"}]},{"id":"4718","type":"Chemical","text":["glutathione"],"offsets":[[929,940]],"normalized":[{"db_name":"MESH","db_id":"D005978"}]},{"id":"4719","type":"Chemical","text":["glutathione"],"offsets":[[953,964]],"normalized":[{"db_name":"MESH","db_id":"D005978"}]},{"id":"4720","type":"Chemical","text":["glutathione"],"offsets":[[981,992]],"normalized":[{"db_name":"MESH","db_id":"D005978"}]},{"id":"4721","type":"Chemical","text":["Vitamin C"],"offsets":[[1064,1073]],"normalized":[{"db_name":"MESH","db_id":"D001205"}]},{"id":"4722","type":"Chemical","text":["Vitamin E"],"offsets":[[1075,1084]],"normalized":[{"db_name":"MESH","db_id":"D014810"}]},{"id":"4723","type":"Chemical","text":["glutathione"],"offsets":[[1089,1100]],"normalized":[{"db_name":"MESH","db_id":"D005978"}]},{"id":"4724","type":"Disease","text":["MI"],"offsets":[[1124,1126]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"4725","type":"Chemical","text":["mangiferin"],"offsets":[[1156,1166]],"normalized":[{"db_name":"MESH","db_id":"C013592"}]},{"id":"4726","type":"Chemical","text":["dimethyl sulphoxide"],"offsets":[[1211,1230]],"normalized":[{"db_name":"MESH","db_id":"D004121"}]},{"id":"4727","type":"Disease","text":["MI"],"offsets":[[1271,1273]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"4728","type":"Chemical","text":["mangiferin"],"offsets":[[1466,1476]],"normalized":[{"db_name":"MESH","db_id":"C013592"}]},{"id":"4729","type":"Chemical","text":["ISPH"],"offsets":[[1507,1511]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"4730","type":"Disease","text":["MI"],"offsets":[[1520,1522]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"4731","type":"Chemical","text":["mangiferin"],"offsets":[[1573,1583]],"normalized":[{"db_name":"MESH","db_id":"C013592"}]},{"id":"4732","type":"Chemical","text":["ISPH"],"offsets":[[1619,1623]],"normalized":[{"db_name":"MESH","db_id":"D007545"}]},{"id":"4733","type":"Disease","text":["MI"],"offsets":[[1632,1634]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"4734","type":"Disease","text":["cardiac damage"],"offsets":[[1720,1734]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]}],"events":[],"coreferences":[],"relations":[{"id":"4735","type":"CID","arg1_id":"4699","arg2_id":"4700","normalized":[]},{"id":"4736","type":"CID","arg1_id":"4699","arg2_id":"4705","normalized":[]},{"id":"4737","type":"CID","arg1_id":"4699","arg2_id":"4706","normalized":[]},{"id":"4738","type":"CID","arg1_id":"4699","arg2_id":"4724","normalized":[]},{"id":"4739","type":"CID","arg1_id":"4699","arg2_id":"4727","normalized":[]},{"id":"4740","type":"CID","arg1_id":"4699","arg2_id":"4730","normalized":[]},{"id":"4741","type":"CID","arg1_id":"4699","arg2_id":"4733","normalized":[]},{"id":"4742","type":"CID","arg1_id":"4703","arg2_id":"4700","normalized":[]},{"id":"4743","type":"CID","arg1_id":"4703","arg2_id":"4705","normalized":[]},{"id":"4744","type":"CID","arg1_id":"4703","arg2_id":"4706","normalized":[]},{"id":"4745","type":"CID","arg1_id":"4703","arg2_id":"4724","normalized":[]},{"id":"4746","type":"CID","arg1_id":"4703","arg2_id":"4727","normalized":[]},{"id":"4747","type":"CID","arg1_id":"4703","arg2_id":"4730","normalized":[]},{"id":"4748","type":"CID","arg1_id":"4703","arg2_id":"4733","normalized":[]},{"id":"4749","type":"CID","arg1_id":"4704","arg2_id":"4700","normalized":[]},{"id":"4750","type":"CID","arg1_id":"4704","arg2_id":"4705","normalized":[]},{"id":"4751","type":"CID","arg1_id":"4704","arg2_id":"4706","normalized":[]},{"id":"4752","type":"CID","arg1_id":"4704","arg2_id":"4724","normalized":[]},{"id":"4753","type":"CID","arg1_id":"4704","arg2_id":"4727","normalized":[]},{"id":"4754","type":"CID","arg1_id":"4704","arg2_id":"4730","normalized":[]},{"id":"4755","type":"CID","arg1_id":"4704","arg2_id":"4733","normalized":[]},{"id":"4756","type":"CID","arg1_id":"4707","arg2_id":"4700","normalized":[]},{"id":"4757","type":"CID","arg1_id":"4707","arg2_id":"4705","normalized":[]},{"id":"4758","type":"CID","arg1_id":"4707","arg2_id":"4706","normalized":[]},{"id":"4759","type":"CID","arg1_id":"4707","arg2_id":"4724","normalized":[]},{"id":"4760","type":"CID","arg1_id":"4707","arg2_id":"4727","normalized":[]},{"id":"4761","type":"CID","arg1_id":"4707","arg2_id":"4730","normalized":[]},{"id":"4762","type":"CID","arg1_id":"4707","arg2_id":"4733","normalized":[]},{"id":"4763","type":"CID","arg1_id":"4729","arg2_id":"4700","normalized":[]},{"id":"4764","type":"CID","arg1_id":"4729","arg2_id":"4705","normalized":[]},{"id":"4765","type":"CID","arg1_id":"4729","arg2_id":"4706","normalized":[]},{"id":"4766","type":"CID","arg1_id":"4729","arg2_id":"4724","normalized":[]},{"id":"4767","type":"CID","arg1_id":"4729","arg2_id":"4727","normalized":[]},{"id":"4768","type":"CID","arg1_id":"4729","arg2_id":"4730","normalized":[]},{"id":"4769","type":"CID","arg1_id":"4729","arg2_id":"4733","normalized":[]},{"id":"4770","type":"CID","arg1_id":"4732","arg2_id":"4700","normalized":[]},{"id":"4771","type":"CID","arg1_id":"4732","arg2_id":"4705","normalized":[]},{"id":"4772","type":"CID","arg1_id":"4732","arg2_id":"4706","normalized":[]},{"id":"4773","type":"CID","arg1_id":"4732","arg2_id":"4724","normalized":[]},{"id":"4774","type":"CID","arg1_id":"4732","arg2_id":"4727","normalized":[]},{"id":"4775","type":"CID","arg1_id":"4732","arg2_id":"4730","normalized":[]},{"id":"4776","type":"CID","arg1_id":"4732","arg2_id":"4733","normalized":[]}]}
{"id":"4777","document_id":"16563323","passages":[{"id":"4778","type":"title","text":["Remifentanil pretreatment reduces myoclonus after etomidate."],"offsets":[[0,60]]},{"id":"4779","type":"abstract","text":["STUDY OBJECTIVE: The aim of the study was to compare the effect of pretreatment with remifentanil 1 microg\/kg and the effect of gender on the incidence of myoclonus after anesthesia induction with etomidate. DESIGN: This was a randomized, double-blind study. SETTING: The study was conducted at a university hospital. PATIENTS: Sixty patients were pretreated in a randomized double-blinded fashion with remifentanil 1 microg\/kg or placebo. Two minutes after remifentanil or placebo injection, etomidate 0.3 mg\/kg was given. MEASUREMENTS: Myoclonus was recorded with a scale of 0 to 3. The grade of sedation (none, mild, moderate, severe), nausea, pruritus, and apnea were recorded after injection of both drugs. MAIN RESULTS: The incidence of myoclonus was significantly lower in the remifentanil group (6.7%) than in the placebo group (70%) (P < 0.001). None of the patients experienced sedation, apnea, nausea, or pruritus after injection of both drugs. In the placebo group, male patients were associated with significantly increased incidence of myoclonus after etomidate administration. CONCLUSION: Pretreatment with remifentanil 1 microg\/kg reduced myoclonus after etomidate induction without side effects such as sedation, apnea, nausea, or pruritus. Men experience increased incidence of myoclonus than women after etomidate administration."],"offsets":[[61,1409]]}],"entities":[{"id":"4780","type":"Chemical","text":["Remifentanil"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"C071741"}]},{"id":"4781","type":"Disease","text":["myoclonus"],"offsets":[[34,43]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"4782","type":"Chemical","text":["etomidate"],"offsets":[[50,59]],"normalized":[{"db_name":"MESH","db_id":"D005045"}]},{"id":"4783","type":"Chemical","text":["remifentanil"],"offsets":[[146,158]],"normalized":[{"db_name":"MESH","db_id":"C071741"}]},{"id":"4784","type":"Disease","text":["myoclonus"],"offsets":[[216,225]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"4785","type":"Chemical","text":["etomidate"],"offsets":[[258,267]],"normalized":[{"db_name":"MESH","db_id":"D005045"}]},{"id":"4786","type":"Chemical","text":["remifentanil"],"offsets":[[464,476]],"normalized":[{"db_name":"MESH","db_id":"C071741"}]},{"id":"4787","type":"Chemical","text":["remifentanil"],"offsets":[[519,531]],"normalized":[{"db_name":"MESH","db_id":"C071741"}]},{"id":"4788","type":"Chemical","text":["etomidate"],"offsets":[[554,563]],"normalized":[{"db_name":"MESH","db_id":"D005045"}]},{"id":"4789","type":"Disease","text":["Myoclonus"],"offsets":[[599,608]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"4790","type":"Disease","text":["nausea"],"offsets":[[700,706]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"4791","type":"Disease","text":["pruritus"],"offsets":[[708,716]],"normalized":[{"db_name":"MESH","db_id":"D011537"}]},{"id":"4792","type":"Disease","text":["apnea"],"offsets":[[722,727]],"normalized":[{"db_name":"MESH","db_id":"D001049"}]},{"id":"4793","type":"Disease","text":["myoclonus"],"offsets":[[804,813]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"4794","type":"Chemical","text":["remifentanil"],"offsets":[[845,857]],"normalized":[{"db_name":"MESH","db_id":"C071741"}]},{"id":"4795","type":"Disease","text":["apnea"],"offsets":[[959,964]],"normalized":[{"db_name":"MESH","db_id":"D001049"}]},{"id":"4796","type":"Disease","text":["nausea"],"offsets":[[966,972]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"4797","type":"Disease","text":["pruritus"],"offsets":[[977,985]],"normalized":[{"db_name":"MESH","db_id":"D011537"}]},{"id":"4798","type":"Disease","text":["myoclonus"],"offsets":[[1111,1120]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"4799","type":"Chemical","text":["etomidate"],"offsets":[[1127,1136]],"normalized":[{"db_name":"MESH","db_id":"D005045"}]},{"id":"4800","type":"Chemical","text":["remifentanil"],"offsets":[[1183,1195]],"normalized":[{"db_name":"MESH","db_id":"C071741"}]},{"id":"4801","type":"Disease","text":["myoclonus"],"offsets":[[1216,1225]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"4802","type":"Chemical","text":["etomidate"],"offsets":[[1232,1241]],"normalized":[{"db_name":"MESH","db_id":"D005045"}]},{"id":"4803","type":"Disease","text":["apnea"],"offsets":[[1291,1296]],"normalized":[{"db_name":"MESH","db_id":"D001049"}]},{"id":"4804","type":"Disease","text":["nausea"],"offsets":[[1298,1304]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"4805","type":"Disease","text":["pruritus"],"offsets":[[1309,1317]],"normalized":[{"db_name":"MESH","db_id":"D011537"}]},{"id":"4806","type":"Disease","text":["myoclonus"],"offsets":[[1357,1366]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"4807","type":"Chemical","text":["etomidate"],"offsets":[[1384,1393]],"normalized":[{"db_name":"MESH","db_id":"D005045"}]}],"events":[],"coreferences":[],"relations":[{"id":"4808","type":"CID","arg1_id":"4782","arg2_id":"4781","normalized":[]},{"id":"4809","type":"CID","arg1_id":"4782","arg2_id":"4784","normalized":[]},{"id":"4810","type":"CID","arg1_id":"4782","arg2_id":"4789","normalized":[]},{"id":"4811","type":"CID","arg1_id":"4782","arg2_id":"4793","normalized":[]},{"id":"4812","type":"CID","arg1_id":"4782","arg2_id":"4798","normalized":[]},{"id":"4813","type":"CID","arg1_id":"4782","arg2_id":"4801","normalized":[]},{"id":"4814","type":"CID","arg1_id":"4782","arg2_id":"4806","normalized":[]},{"id":"4815","type":"CID","arg1_id":"4785","arg2_id":"4781","normalized":[]},{"id":"4816","type":"CID","arg1_id":"4785","arg2_id":"4784","normalized":[]},{"id":"4817","type":"CID","arg1_id":"4785","arg2_id":"4789","normalized":[]},{"id":"4818","type":"CID","arg1_id":"4785","arg2_id":"4793","normalized":[]},{"id":"4819","type":"CID","arg1_id":"4785","arg2_id":"4798","normalized":[]},{"id":"4820","type":"CID","arg1_id":"4785","arg2_id":"4801","normalized":[]},{"id":"4821","type":"CID","arg1_id":"4785","arg2_id":"4806","normalized":[]},{"id":"4822","type":"CID","arg1_id":"4788","arg2_id":"4781","normalized":[]},{"id":"4823","type":"CID","arg1_id":"4788","arg2_id":"4784","normalized":[]},{"id":"4824","type":"CID","arg1_id":"4788","arg2_id":"4789","normalized":[]},{"id":"4825","type":"CID","arg1_id":"4788","ar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{"id":"4850","document_id":"16428827","passages":[{"id":"4851","type":"title","text":["Daidzein activates choline acetyltransferase from MC-IXC cells and improves drug-induced amnesia."],"offsets":[[0,97]]},{"id":"4852","type":"abstract","text":["The choline acetyltransferase (ChAT) activator, which enhances cholinergic transmission via an augmentation of the enzymatic production of acetylcholine (ACh), is an important factor in the treatment of Alzheimer's disease (AD). Methanolic extracts from Pueraria thunbergiana exhibited an activation effect (46%) on ChAT in vitro. Via the sequential isolation of Pueraria thunbergiana, the active component was ultimately identified as daidzein (4',7-dihydroxy-isoflavone). In order to investigate the effects of daidzein from Pueraria thunbergiana on scopolamine-induced impairments of learning and memory, we conducted a series of in vivo tests. Administration of daidzein (4.5 mg\/kg body weight) to mice was shown significantly to reverse scopolamine-induced amnesia, according to the results of a Y-maze test. Injections of scopolamine into mice resulted in impaired performance on Y-maze tests (a 37% decreases in alternation behavior). By way of contrast, mice treated with daidzein prior to the scopolamine injections were noticeably protected from this performance impairment (an approximately 12%-21% decrease in alternation behavior). These results indicate that daidzein might play a role in acetylcholine biosynthesis as a ChAT activator, and that it also ameliorates scopolamine-induced amnesia."],"offsets":[[98,1406]]}],"entities":[{"id":"4853","type":"Chemical","text":["Daidzein"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"C004742"}]},{"id":"4854","type":"Chemical","text":["choline"],"offsets":[[19,26]],"normalized":[{"db_name":"MESH","db_id":"D002794"}]},{"id":"4855","type":"Disease","text":["amnesia"],"offsets":[[89,96]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"4856","type":"Chemical","text":["choline"],"offsets":[[102,109]],"normalized":[{"db_name":"MESH","db_id":"D002794"}]},{"id":"4857","type":"Chemical","text":["acetylcholine"],"offsets":[[237,250]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"4858","type":"Chemical","text":["ACh"],"offsets":[[252,255]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"4859","type":"Disease","text":["Alzheimer's disease"],"offsets":[[301,320]],"normalized":[{"db_name":"MESH","db_id":"D000544"}]},{"id":"4860","type":"Disease","text":["AD"],"offsets":[[322,324]],"normalized":[{"db_name":"MESH","db_id":"D000544"}]},{"id":"4861","type":"Chemical","text":["daidzein"],"offsets":[[534,542]],"normalized":[{"db_name":"MESH","db_id":"C004742"}]},{"id":"4862","type":"Chemical","text":["4',7-dihydroxy-isoflavone"],"offsets":[[544,569]],"normalized":[{"db_name":"MESH","db_id":"C004742"}]},{"id":"4863","type":"Chemical","text":["daidzein"],"offsets":[[611,619]],"normalized":[{"db_name":"MESH","db_id":"C004742"}]},{"id":"4864","type":"Chemical","text":["scopolamine"],"offsets":[[650,661]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"4865","type":"Disease","text":["impairments of learning and memory"],"offsets":[[670,704]],"normalized":[{"db_name":"MESH","db_id":"D007859"},{"db_name":"MESH","db_id":"D008569"}]},{"id":"4866","type":"Disease","text":["impairments of learning"],"offsets":[[670,693]],"normalized":[{"db_name":"MESH","db_id":"D007859"}]},{"id":"4867","type":"Disease","text":["impairments of","memory"],"offsets":[[670,684],[698,704]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"4868","type":"Chemical","text":["daidzein"],"offsets":[[764,772]],"normalized":[{"db_name":"MESH","db_id":"C004742"}]},{"id":"4869","type":"Chemical","text":["scopolamine"],"offsets":[[840,851]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"4870","type":"Disease","text":["amnesia"],"offsets":[[860,867]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"4871","type":"Chemical","text":["scopolamine"],"offsets":[[926,937]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"4872","type":"Chemical","text":["daidzein"],"offsets":[[1078,1086]],"normalized":[{"db_name":"MESH","db_id":"C004742"}]},{"id":"4873","type":"Chemical","text":["scopolamine"],"offsets":[[1100,1111]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"4874","type":"Chemical","text":["daidzein"],"offsets":[[1271,1279]],"normalized":[{"db_name":"MESH","db_id":"C004742"}]},{"id":"4875","type":"Chemical","text":["acetylcholine"],"offsets":[[1301,1314]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"4876","type":"Chemical","text":["scopolamine"],"offsets":[[1378,1389]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"4877","type":"Disease","text":["amnesia"],"offsets":[[1398,1405]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]}],"events":[],"coreferences":[],"relations":[{"id":"4878","type":"CID","arg1_id":"4864","arg2_id":"4855","normalized":[]},{"id":"4879","type":"CID","arg1_id":"4864","arg2_id":"4870","normalized":[]},{"id":"4880","type":"CID","arg1_id":"4864","arg2_id":"4877","normalized":[]},{"id":"4881","type":"CID","arg1_id":"4869","arg2_id":"4855","normalized":[]},{"id":"4882","type":"CID","arg1_id":"4869","arg2_id":"4870","normalized":[]},{"id":"4883","type":"CID","arg1_id":"4869","arg2_id":"4877","normalized":[]},{"id":"4884","type":"CID","arg1_id":"4871","arg2_id":"4855","normalized":[]},{"id":"4885","type":"CID","arg1_id":"4871","arg2_id":"4870","normalized":[]},{"id":"4886","type":"CID","arg1_id":"4871","arg2_id":"4877","normalized":[]},{"id":"4887","type":"CID","arg1_id":"4873","arg2_id":"4855","normalized":[]},{"id":"4888","type":"CID","arg1_id":"4873","arg2_id":"4870","normalized":[]},{"id":"4889","type":"CID","arg1_id":"4873","arg2_id":"4877","normalized":[]},{"id":"4890","type":"CID","arg1_id":"4876","arg2_id":"4855","normalized":[]},{"id":"4891","type":"CID","arg1_id":"4876","arg2_id":"4870","normalized":[]},{"id":"4892","type":"CID","arg1_id":"4876","arg2_id":"4877","normalized":[]}]}
{"id":"4893","document_id":"15985056","passages":[{"id":"4894","type":"title","text":["Possible azithromycin-associated hiccups."],"offsets":[[0,41]]},{"id":"4895","type":"abstract","text":["OBJECTIVE: To report a case of persistent hiccups associated by azithromycin therapy. CASE SUMMARY: A 76-year-old man presented with persistent hiccups after beginning azithromycin for the treatment of pharyngitis. Hiccups were persistent and exhausting. Discontinuation of azithromycin and therapy with baclofen finally resolved hiccups. No organic cause of hiccups was identified despite extensive investigation. DISCUSSION: Pharmacotherapeutic agents have been uncommonly associated with hiccups. Corticosteroids (dexamethasone and methylprednisolone), benzodiazepines (midazolam) and general anaesthesia have been the specific agents mentioned most frequently in the literature as being associated with the development of hiccups. Few cases of drug-induced hiccups have been reported related to macrolide antimicrobials. Using the Naranjo adverse effect reaction probability scale this event could be classified as possible (score 5 points), mostly because of the close temporal sequence, previous reports on this reaction with other macrolides and the absence of any alternative explanation for hiccups. Our hypothesis is that a vagal mechanism mediated by azithromycin could be the pathogenesis of hiccups in our patient. CONCLUSIONS: Diagnosis of drug-induced hiccups is difficult and often achieved only by a process of elimination. However, macrolide antimicrobials have been reported to be associated with hiccups and vagal mechanism could explain the development of this side-effect."],"offsets":[[42,1536]]}],"entities":[{"id":"4896","type":"Chemical","text":["azithromycin"],"offsets":[[9,21]],"normalized":[{"db_name":"MESH","db_id":"D017963"}]},{"id":"4897","type":"Disease","text":["hiccups"],"offsets":[[33,40]],"normalized":[{"db_name":"MESH","db_id":"D006606"}]},{"id":"4898","type":"Disease","text":["hiccups"],"offsets":[[84,91]],"normalized":[{"db_name":"MESH","db_id":"D006606"}]},{"id":"4899","type":"Chemical","text":["azithromycin"],"offsets":[[106,118]],"normalized":[{"db_name":"MESH","db_id":"D017963"}]},{"id":"4900","type":"Disease","text":["hiccups"],"offsets":[[186,193]],"normalized":[{"db_name":"MESH","db_id":"D006606"}]},{"id":"4901","type":"Chemical","text":["azithromycin"],"offsets":[[210,222]],"normalized":[{"db_name":"MESH","db_id":"D017963"}]},{"id":"4902","type":"Disease","text":["pharyngitis"],"offsets":[[244,255]],"normalized":[{"db_name":"MESH","db_id":"D010612"}]},{"id":"4903","type":"Disease","text":["Hiccups"],"offsets":[[257,264]],"normalized":[{"db_name":"MESH","db_id":"D006606"}]},{"id":"4904","type":"Chemical","text":["azithromycin"],"offsets":[[316,328]],"normalized":[{"db_name":"MESH","db_id":"D017963"}]},{"id":"4905","type":"Chemical","text":["baclofen"],"offsets":[[346,354]],"normalized":[{"db_name":"MESH","db_id":"D001418"}]},{"id":"4906","type":"Disease","text":["hiccups"],"offsets":[[372,379]],"normalized":[{"db_name":"MESH","db_id":"D006606"}]},{"id":"4907","type":"Disease","text":["hiccups"],"offsets":[[401,408]],"normalized":[{"db_name":"MESH","db_id":"D006606"}]},{"id":"4908","type":"Disease","text":["hiccups"],"offsets":[[533,540]],"normalized":[{"db_name":"MESH","db_id":"D006606"}]},{"id":"4909","type":"Chemical","text":["dexamethasone"],"offsets":[[559,572]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"4910","type":"Chemical","text":["methylprednisolone"],"offsets":[[577,595]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"4911","type":"Chemical","text":["benzodiazepines"],"offsets":[[598,613]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]},{"id":"4912","type":"Chemical","text":["midazolam"],"offsets":[[615,624]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"4913","type":"Disease","text":["hiccups"],"offsets":[[768,775]],"normalized":[{"db_name":"MESH","db_id":"D006606"}]},{"id":"4914","type":"Disease","text":["hiccups"],"offsets":[[803,810]],"normalized":[{"db_name":"MESH","db_id":"D006606"}]},{"id":"4915","type":"Chemical","text":["macrolide"],"offsets":[[841,850]],"normalized":[{"db_name":"MESH","db_id":"D018942"}]},{"id":"4916","type":"Chemical","text":["macrolides"],"offsets":[[1080,1090]],"normalized":[{"db_name":"MESH","db_id":"D018942"}]},{"id":"4917","type":"Disease","text":["hiccups"],"offsets":[[1142,1149]],"normalized":[{"db_name":"MESH","db_id":"D006606"}]},{"id":"4918","type":"Chemical","text":["azithromycin"],"offsets":[[1204,1216]],"normalized":[{"db_name":"MESH","db_id":"D017963"}]},{"id":"4919","type":"Disease","text":["hiccups"],"offsets":[[1246,1253]],"normalized":[{"db_name":"MESH","db_id":"D006606"}]},{"id":"4920","type":"Disease","text":["hiccups"],"offsets":[[1309,1316]],"normalized":[{"db_name":"MESH","db_id":"D006606"}]},{"id":"4921","type":"Chemical","text":["macrolide"],"offsets":[[1392,1401]],"normalized":[{"db_name":"MESH","db_id":"D018942"}]},{"id":"4922","type":"Disease","text":["hiccups"],"offsets":[[1458,1465]],"normalized":[{"db_name":"MESH","db_id":"D006606"}]}],"events":[],"coreferences":[],"relations":[{"id":"4923","type":"CID","arg1_id":"4896","arg2_id":"4897","normalized":[]},{"id":"4924","type":"CID","arg1_id":"4896","arg2_id":"4898","normalized":[]},{"id":"4925","type":"CID","arg1_id":"4896","arg2_id":"4900","normalized":[]},{"id":"4926","type":"CID","arg1_id":"4896","arg2_id":"4903","normalized":[]},{"id":"4927","type":"CID","arg1_id":"4896","arg2_id":"4906","normalized":[]},{"id":"4928","type":"CID","arg1_id":"4896","arg2_id":"4907","normalized":[]},{"id":"4929","type":"CID","arg1_id":"4896","arg2_id":"4908","normalized":[]},{"id":"4930","type":"CID","arg1_id":"4896","arg2_id":"4913","normalized":[]},{"id":"4931","type":"CID","arg1_id":"4896","arg2_id":"4914","normalized":[]},{"id":"4932","type":"CID","arg1_id":"4896","arg2_id":"4917","normalized":[]},{"id":"4933","type":"CID","arg1_id":"4896","arg2_id":"4919","normalized":[]},{"id":"4934","type":"CID","arg1_id":"4896","arg2_id":"4920","normalized":[]},{"id":"4935","type":"CID","arg1_id":"4896","arg2_id":"4922","normalized":[]},{"id":"4936","type":"CID","arg1_id":"4899","arg2_id":"4897","normalized":[]},{"id":"4937","type":"CID","arg1_id":"4899","arg2_id":"4898","normalized":[]},{"id":"4938","type":"CID","arg1_id":"4899","arg2_id":"4900","normalized":[]},{"id":"4939","type":"CID","arg1_id":"4899","arg2_id":"4903","normalized":[]},{"id":"4940","type":"CID","arg1_id":"4899","arg2_id":"4906","normalized":[]},{"id":"4941","type":"CID","arg1_id":"4899","arg2_id":"4907","normalized":[]},{"id":"494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{"id":"5001","document_id":"15276120","passages":[{"id":"5002","type":"title","text":["Time trends in warfarin-associated hemorrhage."],"offsets":[[0,46]]},{"id":"5003","type":"abstract","text":["The annual incidence of warfarin-related bleeding at Brigham and Women's Hospital increased from 0.97\/1,000 patient admissions in the first time period (January 1995 to October 1998) to 1.19\/1,000 patient admissions in the second time period (November 1998 to August 2002) of this study. The proportion of patients with major and intracranial bleeding increased from 20.2% and 1.9%, respectively, in the first time period, to 33.3% and 7.8%, respectively, in the second."],"offsets":[[47,517]]}],"entities":[{"id":"5004","type":"Chemical","text":["warfarin"],"offsets":[[15,23]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"5005","type":"Disease","text":["hemorrhage"],"offsets":[[35,45]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"5006","type":"Chemical","text":["warfarin"],"offsets":[[71,79]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"5007","type":"Disease","text":["bleeding"],"offsets":[[88,96]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"5008","type":"Disease","text":["intracranial bleeding"],"offsets":[[377,398]],"normalized":[{"db_name":"MESH","db_id":"D020300"}]}],"events":[],"coreferences":[],"relations":[{"id":"5009","type":"CID","arg1_id":"5004","arg2_id":"5008","normalized":[]},{"id":"5010","type":"CID","arg1_id":"5006","arg2_id":"5008","normalized":[]},{"id":"5011","type":"CID","arg1_id":"5004","arg2_id":"5005","normalized":[]},{"id":"5012","type":"CID","arg1_id":"5004","arg2_id":"5007","normalized":[]},{"id":"5013","type":"CID","arg1_id":"5006","arg2_id":"5005","normalized":[]},{"id":"5014","type":"CID","arg1_id":"5006","arg2_id":"5007","normalized":[]}]}
{"id":"5015","document_id":"11271907","passages":[{"id":"5016","type":"title","text":["Fatal haemorrhagic myocarditis secondary to cyclophosphamide therapy."],"offsets":[[0,69]]},{"id":"5017","type":"abstract","text":["Haemorrhagic myocarditis is a rare but important complication of cyclophosphamide therapy. Echocardiographic identification of the disorder can be made. We believe that the ultrasound features of this disorder have not been previously reported."],"offsets":[[70,314]]}],"entities":[{"id":"5018","type":"Disease","text":["haemorrhagic myocarditis"],"offsets":[[6,30]],"normalized":[{"db_name":"MESH","db_id":"D006470"},{"db_name":"MESH","db_id":"D009205"}]},{"id":"5019","type":"Disease","text":["haemorrhagic"],"offsets":[[6,18]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"5020","type":"Disease","text":["myocarditis"],"offsets":[[19,30]],"normalized":[{"db_name":"MESH","db_id":"D009205"}]},{"id":"5021","type":"Chemical","text":["cyclophosphamide"],"offsets":[[44,60]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"5022","type":"Disease","text":["Haemorrhagic myocarditis"],"offsets":[[70,94]],"normalized":[{"db_name":"MESH","db_id":"D006470"},{"db_name":"MESH","db_id":"D009205"}]},{"id":"5023","type":"Disease","text":["Haemorrhagic"],"offsets":[[70,82]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"5024","type":"Disease","text":["myocarditis"],"offsets":[[83,94]],"normalized":[{"db_name":"MESH","db_id":"D009205"}]},{"id":"5025","type":"Chemical","text":["cyclophosphamide"],"offsets":[[135,151]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]}],"events":[],"coreferences":[],"relations":[{"id":"5026","type":"CID","arg1_id":"5021","arg2_id":"5018","normalized":[]},{"id":"5027","type":"CID","arg1_id":"5021","arg2_id":"5020","normalized":[]},{"id":"5028","type":"CID","arg1_id":"5021","arg2_id":"5022","normalized":[]},{"id":"5029","type":"CID","arg1_id":"5021","arg2_id":"5024","normalized":[]},{"id":"5030","type":"CID","arg1_id":"5025","arg2_id":"5018","normalized":[]},{"id":"5031","type":"CID","arg1_id":"5025","arg2_id":"5020","normalized":[]},{"id":"5032","type":"CID","arg1_id":"5025","arg2_id":"5022","normalized":[]},{"id":"5033","type":"CID","arg1_id":"5025","arg2_id":"5024","normalized":[]},{"id":"5034","type":"CID","arg1_id":"5021","arg2_id":"5018","normalized":[]},{"id":"5035","type":"CID","arg1_id":"5021","arg2_id":"5019","normalized":[]},{"id":"5036","type":"CID","arg1_id":"5021","arg2_id":"5022","normalized":[]},{"id":"5037","type":"CID","arg1_id":"5021","arg2_id":"5023","normalized":[]},{"id":"5038","type":"CID","arg1_id":"5025","arg2_id":"5018","normalized":[]},{"id":"5039","type":"CID","arg1_id":"5025","arg2_id":"5019","normalized":[]},{"id":"5040","type":"CID","arg1_id":"5025","arg2_id":"5022","normalized":[]},{"id":"5041","type":"CID","arg1_id":"5025","arg2_id":"5023","normalized":[]}]}
{"id":"5042","document_id":"10524660","passages":[{"id":"5043","type":"title","text":["Glyceryl trinitrate induces attacks of migraine without aura in sufferers of migraine with aura."],"offsets":[[0,96]]},{"id":"5044","type":"abstract","text":["Migraine with aura and migraine without aura have the same pain phase, thus indicating that migraine with aura and migraine without aura share a common pathway of nociception. In recent years, increasing evidence has suggested that the messenger molecule nitric oxide (NO) is involved in pain mechanisms of migraine without aura. In order to clarify whether the same is true for migraine with aura, in the present study we examined the headache response to intravenous infusion of glyceryl trinitrate (GTN) (0.5 microg\/kg\/min for 20 min) in 12 sufferers of migraine with aura. The specific aim was to elucidate whether an aura and\/or an attack of migraine without aura could be induced. Fourteen healthy subjects served as controls. Aura symptoms were not elicited in any subject. Headache was more severe in migraineurs than in the controls during and immediately after GTN infusion (p=0.037) as well as during the following 11 h (p = 0.008). In the controls, the GTN-induced headache gradually disappeared, whereas in migraineurs peak headache intensity occurred at a mean time of 240 min post-infusion. At this time the induced headache in 6 of 12 migraineurs fulfilled the diagnostic criteria for migraine without aura of the International Headache Society. The results therefore suggest that NO is involved in the pain mechanisms of migraine with aura. Since cortical spreading depression has been shown to liberate NO in animals, this finding may help our understanding of the coupling between cortical spreading depression and headache in migraine with aura."],"offsets":[[97,1662]]}],"entities":[{"id":"5045","type":"Chemical","text":["Glyceryl trinitrate"],"offsets":[[0,19]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"5046","type":"Disease","text":["migraine without aura"],"offsets":[[39,60]],"normalized":[{"db_name":"MESH","db_id":"D020326"}]},{"id":"5047","type":"Disease","text":["migraine with aura"],"offsets":[[77,95]],"normalized":[{"db_name":"MESH","db_id":"D020325"}]},{"id":"5048","type":"Disease","text":["Migraine with aura"],"offsets":[[97,115]],"normalized":[{"db_name":"MESH","db_id":"D020325"}]},{"id":"5049","type":"Disease","text":["migraine without 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{"id":"5136","document_id":"9799166","passages":[{"id":"5137","type":"title","text":["Stroke and cocaine or amphetamine use."],"offsets":[[0,38]]},{"id":"5138","type":"abstract","text":["The association of cocaine and amphetamine use with hemorrhagic and ischemic stroke is based almost solely on data from case series. The limited number of epidemiologic studies of stroke and use of cocaine and\/or amphetamine have been done in settings that serve mostly the poor and\/or minorities. This case-control study was conducted in the defined population comprising members of Kaiser Permanente of Northern and Southern California. We attempted to identify all incident strokes in women ages 15-44 years during a 3-year period using hospital admission and discharge records, emergency department logs, and payment requests for out-of-plan hospitalizations. We selected controls, matched on age and facility of usual care, at random from healthy members of the health plan. We obtained information in face-to-face interviews. There were 347 confirmed stroke cases and 1,021 controls. The univariate matched odds ratio for stroke in women who admitted to using cocaine and\/or amphetamine was 8.5 (95% confidence interval = 3.6-20.0). After further adjustment for potential confounders, the odds ratio in women who reported using cocaine and\/or amphetamine was 7.0 (95% confidence interval = 2.8-17.9). The use of cocaine and\/or amphetamine is a strong risk factor for stroke in this socioeconomically heterogeneous, insured urban 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{"id":"5243","document_id":"9672273","passages":[{"id":"5244","type":"title","text":["Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study."],"offsets":[[0,163]]},{"id":"5245","type":"abstract","text":["BACKGROUND: Tamoxifen is a candidate chemopreventive agent in breast cancer, although the drug may be associated with the development of endometrial cancer. Therefore we did a trial in hysterectomised women of tamoxifen as a chemopreventive. METHODS: In October, 1992, we started a double-blind placebo-controlled, randomised trial of tamoxifen in women (mainly in Italy) who did not have breast cancer and who had had a hysterectomy. Women were randomised to receive tamoxifen 20 mg per day or placebo, both orally for 5 years. The original plan was to follow the intervention phase by 5 years' follow-up. In June, 1997, the trialists and the data-monitoring committee decided to end recruitment primarily because of the number of women dropping out of the study. Recruitment ended on July 11, 1997, and the study will continue as planned. The primary endpoints are the occurrence of and deaths from breast cancer. This preliminary interim analysis is based on intention-to-treat. FINDINGS: 5408 women were randomised; participating women have a median follow-up of 46 months for major endpoints. 41 cases of breast cancer occurred so far; there have been no deaths from breast cancer. There is no difference in breast-cancer frequency between the placebo (22 cases) and tamoxifen (19) arms. There is a statistically significant reduction of breast cancer among women receiving tamoxifen who also used hormone-replacement therapy during the trial: among 390 women on such therapy and allocated to placebo, we found eight cases of breast cancer compared with one case among 362 women allocated to tamoxifen. Compared with the placebo group, there was a significantly increased risk of vascular events and hypertriglyceridaemia among women on tamoxifen. INTERPRETATION: Although this preliminary analysis has low power, in this cohort of women at low-to-normal risk of breast cancer, the postulated protective effects of tamoxifen are not yet apparent. Women using hormone-replacement therapy appear to have benefited from use of tamoxifen. There were no deaths from breast cancer recorded in women in the study. It is essential to continue follow-up to quantify the long-term risks and benefits of tamoxifen therapy."],"offsets":[[164,2380]]}],"entities":[{"id":"5246","type":"Disease","text":["breast cancer"],"offsets":[[14,27]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"5247","type":"Chemical","text":["tamoxifen"],"offsets":[[33,42]],"normalized":[{"db_name":"MESH","db_id":"D013629"}]},{"id":"5248","type":"Chemical","text":["Tamoxifen"],"offsets":[[136,145]],"normalized":[{"db_name":"MESH","db_id":"D013629"}]},{"id":"5249","type":"Chemical","text":["Tamoxifen"],"offsets":[[176,185]],"normalized":[{"db_name":"MESH","db_id":"D013629"}]},{"id":"5250","type":"Disease","text":["breast cancer"],"offsets":[[226,239]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"5251","type":"Disease","text":["endometrial 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{"id":"5299","document_id":"8854309","passages":[{"id":"5300","type":"title","text":["A measure of pupillary oscillation as a marker of cocaine-induced paranoia."],"offsets":[[0,75]]},{"id":"5301","type":"abstract","text":["Cocaine-induced paranoia (CIP) remains an important drug-induced model of idiopathic paranoia for which no psychophysiologic marker has yet emerged. Measures of pupillary oscillation were able to significantly distinguish a group of abstinent crack cocaine abusers endorsing past CIP (n = 32) from another group of crack addicts who denied past CIP (n = 29)."],"offsets":[[76,434]]}],"entities":[{"id":"5302","type":"Disease","text":["pupillary oscillation"],"offsets":[[13,34]],"normalized":[{"db_name":"MESH","db_id":"D011681"}]},{"id":"5303","type":"Chemical","text":["cocaine"],"offsets":[[50,57]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"5304","type":"Disease","text":["paranoia"],"offsets":[[66,74]],"normalized":[{"db_name":"MESH","db_id":"D010259"}]},{"id":"5305","type":"Chemical","text":["Cocaine"],"offsets":[[76,83]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"5306","type":"Disease","text":["paranoia"],"offsets":[[92,100]],"normalized":[{"db_name":"MESH","db_id":"D010259"}]},{"id":"5307","type":"Disease","text":["CIP"],"offsets":[[102,105]],"normalized":[{"db_name":"MESH","db_id":"D010259"}]},{"id":"5308","type":"Disease","text":["paranoia"],"offsets":[[161,169]],"normalized":[{"db_name":"MESH","db_id":"D010259"}]},{"id":"5309","type":"Disease","text":["pupillary oscillation"],"offsets":[[237,258]],"normalized":[{"db_name":"MESH","db_id":"D011681"}]},{"id":"5310","type":"Chemical","text":["crack cocaine"],"offsets":[[319,332]],"normalized":[{"db_name":"MESH","db_id":"D016578"}]},{"id":"5311","type":"Disease","text":["CIP"],"offsets":[[356,359]],"normalized":[{"db_name":"MESH","db_id":"D010259"}]},{"id":"5312","type":"Chemical","text":["crack"],"offsets":[[391,396]],"normalized":[{"db_name":"MESH","db_id":"D016578"}]},{"id":"5313","type":"Disease","text":["CIP"],"offsets":[[421,424]],"normalized":[{"db_name":"MESH","db_id":"D010259"}]}],"events":[],"coreferences":[],"relations":[{"id":"5314","type":"CID","arg1_id":"5303","arg2_id":"5302","normalized":[]},{"id":"5315","type":"CID","arg1_id":"5303","arg2_id":"5309","normalized":[]},{"id":"5316","type":"CID","arg1_id":"5305","arg2_id":"5302","normalized":[]},{"id":"5317","type":"CID","arg1_id":"5305","arg2_id":"5309","normalized":[]},{"id":"5318","type":"CID","arg1_id":"5303","arg2_id":"5304","normalized":[]},{"id":"5319","type":"CID","arg1_id":"5303","arg2_id":"5306","normalized":[]},{"id":"5320","type":"CID","arg1_id":"5303","arg2_id":"5307","normalized":[]},{"id":"5321","type":"CID","arg1_id":"5303","arg2_id":"5308","normalized":[]},{"id":"5322","type":"CID","arg1_id":"5303","arg2_id":"5311","normalized":[]},{"id":"5323","type":"CID","arg1_id":"5303","arg2_id":"5313","normalized":[]},{"id":"5324","type":"CID","arg1_id":"5305","arg2_id":"5304","normalized":[]},{"id":"5325","type":"CID","arg1_id":"5305","arg2_id":"5306","normalized":[]},{"id":"5326","type":"CID","arg1_id":"5305","arg2_id":"5307","normalized":[]},{"id":"5327","type":"CID","arg1_id":"5305","arg2_id":"5308","normalized":[]},{"id":"5328","type":"CID","arg1_id":"5305","arg2_id":"5311","normalized":[]},{"id":"5329","type":"CID","arg1_id":"5305","arg2_id":"5313","normalized":[]}]}
{"id":"5330","document_id":"8473723","passages":[{"id":"5331","type":"title","text":["Seizures induced by combined levomepromazine-fluvoxamine treatment."],"offsets":[[0,67]]},{"id":"5332","type":"abstract","text":["We report a case of combined levomepromazine-fluvoxamine treatment-induced seizures. It seems that combined treatment of fluvoxamine with phenothiazines may possess proconvulsive activity."],"offsets":[[68,256]]}],"entities":[{"id":"5333","type":"Disease","text":["Seizures"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"5334","type":"Chemical","text":["levomepromazine"],"offsets":[[29,44]],"normalized":[{"db_name":"MESH","db_id":"D008728"}]},{"id":"5335","type":"Chemical","text":["fluvoxamine"],"offsets":[[45,56]],"normalized":[{"db_name":"MESH","db_id":"D016666"}]},{"id":"5336","type":"Chemical","text":["levomepromazine"],"offsets":[[97,112]],"normalized":[{"db_name":"MESH","db_id":"D008728"}]},{"id":"5337","type":"Chemical","text":["fluvoxamine"],"offsets":[[113,124]],"normalized":[{"db_name":"MESH","db_id":"D016666"}]},{"id":"5338","type":"Disease","text":["seizures"],"offsets":[[143,151]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"5339","type":"Chemical","text":["fluvoxamine"],"offsets":[[189,200]],"normalized":[{"db_name":"MESH","db_id":"D016666"}]},{"id":"5340","type":"Chemical","text":["phenothiazines"],"offsets":[[206,220]],"normalized":[{"db_name":"MESH","db_id":"D010640"}]}],"events":[],"coreferences":[],"relations":[{"id":"5341","type":"CID","arg1_id":"5335","arg2_id":"5333","normalized":[]},{"id":"5342","type":"CID","arg1_id":"5335","arg2_id":"5338","normalized":[]},{"id":"5343","type":"CID","arg1_id":"5337","arg2_id":"5333","normalized":[]},{"id":"5344","type":"CID","arg1_id":"5337","arg2_id":"5338","normalized":[]},{"id":"5345","type":"CID","arg1_id":"5339","arg2_id":"5333","normalized":[]},{"id":"5346","type":"CID","arg1_id":"5339","arg2_id":"5338","normalized":[]},{"id":"5347","type":"CID","arg1_id":"5334","arg2_id":"5333","normalized":[]},{"id":"5348","type":"CID","arg1_id":"5334","arg2_id":"5338","normalized":[]},{"id":"5349","type":"CID","arg1_id":"5336","arg2_id":"5333","normalized":[]},{"id":"5350","type":"CID","arg1_id":"5336","arg2_id":"5338","normalized":[]}]}
{"id":"5351","document_id":"6674249","passages":[{"id":"5352","type":"title","text":["Why may epsilon-aminocaproic acid (EACA) induce myopathy in man? Report of a case and literature review."],"offsets":[[0,104]]},{"id":"5353","type":"abstract","text":["A case of necrotizing myopathy due to a short epsilon-aminocaproic acid (EACA) treatment in a 72 year-old patient with subarachnoid haemorrhage (SAH) is described. Pathogenetic hypotheses are discussed."],"offsets":[[105,307]]}],"entities":[{"id":"5354","type":"Chemical","text":["epsilon-aminocaproic acid"],"offsets":[[8,33]],"normalized":[{"db_name":"MESH","db_id":"D015119"}]},{"id":"5355","type":"Chemical","text":["EACA"],"offsets":[[35,39]],"normalized":[{"db_name":"MESH","db_id":"D015119"}]},{"id":"5356","type":"Disease","text":["myopathy"],"offsets":[[48,56]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"5357","type":"Disease","text":["necrotizing myopathy"],"offsets":[[115,135]],"normalized":[{"db_name":"MESH","db_id":"D009336"},{"db_name":"MESH","db_id":"D009135"}]},{"id":"5358","type":"Disease","text":["necrotizing"],"offsets":[[115,126]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"5359","type":"Disease","text":["myopathy"],"offsets":[[127,135]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"5360","type":"Chemical","text":["epsilon-aminocaproic acid"],"offsets":[[151,176]],"normalized":[{"db_name":"MESH","db_id":"D015119"}]},{"id":"5361","type":"Chemical","text":["EACA"],"offsets":[[178,182]],"normalized":[{"db_name":"MESH","db_id":"D015119"}]},{"id":"5362","type":"Disease","text":["subarachnoid haemorrhage"],"offsets":[[224,248]],"normalized":[{"db_name":"MESH","db_id":"D013345"}]},{"id":"5363","type":"Disease","text":["SAH"],"offsets":[[250,253]],"normalized":[{"db_name":"MESH","db_id":"D013345"}]}],"events":[],"coreferences":[],"relations":[{"id":"5364","type":"CID","arg1_id":"5354","arg2_id":"5357","normalized":[]},{"id":"5365","type":"CID","arg1_id":"5354","arg2_id":"5358","normalized":[]},{"id":"5366","type":"CID","arg1_id":"5355","arg2_id":"5357","normalized":[]},{"id":"5367","type":"CID","arg1_id":"5355","arg2_id":"5358","normalized":[]},{"id":"5368","type":"CID","arg1_id":"5360","arg2_id":"5357","normalized":[]},{"id":"5369","type":"CID","arg1_id":"5360","arg2_id":"5358","normalized":[]},{"id":"5370","type":"CID","arg1_id":"5361","arg2_id":"5357","normalized":[]},{"id":"5371","type":"CID","arg1_id":"5361","arg2_id":"5358","normalized":[]},{"id":"5372","type":"CID","arg1_id":"5354","arg2_id":"5356","normalized":[]},{"id":"5373","type":"CID","arg1_id":"5354","arg2_id":"5357","normalized":[]},{"id":"5374","type":"CID","arg1_id":"5354","arg2_id":"5359","normalized":[]},{"id":"5375","type":"CID","arg1_id":"5355","arg2_id":"5356","normalized":[]},{"id":"5376","type":"CID","arg1_id":"5355","arg2_id":"5357","normalized":[]},{"id":"5377","type":"CID","arg1_id":"5355","arg2_id":"5359","normalized":[]},{"id":"5378","type":"CID","arg1_id":"5360","arg2_id":"5356","normalized":[]},{"id":"5379","type":"CID","arg1_id":"5360","arg2_id":"5357","normalized":[]},{"id":"5380","type":"CID","arg1_id":"5360","arg2_id":"5359","normalized":[]},{"id":"5381","type":"CID","arg1_id":"5361","arg2_id":"5356","normalized":[]},{"id":"5382","type":"CID","arg1_id":"5361","arg2_id":"5357","normalized":[]},{"id":"5383","type":"CID","arg1_id":"5361","arg2_id":"5359","normalized":[]}]}
{"id":"5384","document_id":"6150641","passages":[{"id":"5385","type":"title","text":["Comparison of the effectiveness of ranitidine and cimetidine in inhibiting acid secretion in patients with gastric hypersecretory states."],"offsets":[[0,137]]},{"id":"5386","type":"abstract","text":["The H2-histamine receptor antagonists ranitidine and cimetidine were compared for their abilities to control gastric acid hypersecretion on a short- and long-term basis in 22 patients with gastric acid hypersecretory states. Nineteen patients had Zollinger-Ellison syndrome, one patient had systemic mastocytosis, and two patients had idiopathic hypersecretion. The rates of onset of the action of cimetidine and ranitidine were the same. The actions of both drugs were increased by anticholinergic agents, and there was a close correlation between the daily maintenance dose of each drug needed to control acid secretion. However, ranitidine was threefold more potent than cimetidine both in acute inhibition studies and in the median maintenance dose needed (1.2 g per day for ranitidine and 3.6 g per day for cimetidine). Sixty percent of the males developed breast changes or impotence while taking cimetidine and in all cases these changes disappeared when cimetidine was replaced by ranitidine. Treatment with high doses of cimetidine (one to 60 months; median, 11 months) or ranitidine (two to 31 months; median, 14 months) was not associated with hepatic or hematologic toxicity or alterations of serum gastrin concentrations, but ranitidine therapy was associated with a significantly lower serum creatinine level than seen with cimetidine therapy. The results show that both drugs can adequately inhibit acid secretion in patients with gastric hypersecretory states. Both are safe at high doses, but ranitidine is threefold more potent and does not cause the antiandrogen side effects frequently seen with high doses of cimetidine."],"offsets":[[138,1779]]}],"entities":[{"id":"5387","type":"Chemical","text":["ranitidine"],"offsets":[[35,45]],"normalized":[{"db_name":"MESH","db_id":"D011899"}]},{"id":"5388","type":"Chemical","text":["cimetidine"],"offsets":[[50,60]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"5389","type":"Chemical","text":["histamine"],"offsets":[[145,154]],"normalized":[{"db_name":"MESH","db_id":"D006632"}]},{"id":"5390","type":"Chemical","text":["ranitidine"],"offsets":[[176,186]],"normalized":[{"db_name":"MESH","db_id":"D011899"}]},{"id":"5391","type":"Chemical","text":["cimetidine"],"offsets":[[191,201]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"5392","type":"Disease","text":["Zollinger-Ellison syndrome"],"offsets":[[385,411]],"normalized":[{"db_name":"MESH","db_id":"D015043"}]},{"id":"5393","type":"Disease","text":["systemic mastocytosis"],"offsets":[[429,450]],"normalized":[{"db_name":"MESH","db_id":"D034721"}]},{"id":"5394","type":"Chemical","text":["cimetidine"],"offsets":[[536,546]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"5395","type":"Chemical","text":["ranitidine"],"offsets":[[551,561]],"normalized":[{"db_name":"MESH","db_id":"D011899"}]},{"id":"5396","type":"Chemical","text":["ranitidine"],"offsets":[[770,780]],"normalized":[{"db_name":"MESH","db_id":"D011899"}]},{"id":"5397","type":"Chemical","text":["cimetidine"],"offsets":[[812,822]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"5398","type":"Chemical","text":["ranitidine"],"offsets":[[917,927]],"normalized":[{"db_name":"MESH","db_id":"D011899"}]},{"id":"5399","type":"Chemical","text":["cimetidine"],"offsets":[[950,960]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"5400","type":"Disease","text":["impotence"],"offsets":[[1018,1027]],"normalized":[{"db_name":"MESH","db_id":"D007172"}]},{"id":"5401","type":"Chemical","text":["cimetidine"],"offsets":[[1041,1051]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"5402","type":"Chemical","text":["cimetidine"],"offsets":[[1100,1110]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"5403","type":"Chemical","text":["ranitidine"],"offsets":[[1127,1137]],"normalized":[{"db_name":"MESH","db_id":"D011899"}]},{"id":"5404","type":"Chemical","text":["cimetidine"],"offsets":[[1168,1178]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"5405","type":"Chemical","text":["ranitidine"],"offsets":[[1220,1230]],"normalized":[{"db_name":"MESH","db_id":"D011899"}]},{"id":"5406","type":"Disease","text":["hepatic or hematologic toxicity"],"offsets":[[1293,1324]],"normalized":[{"db_name":"MESH","db_id":"D056486"},{"db_name":"MESH","db_id":"D006402"}]},{"id":"5407","type":"Disease","text":["hepatic","toxicity"],"offsets":[[1293,1300],[1316,1324]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"5408","type":"Disease","text":["hematologic toxicity"],"offsets":[[1304,1324]],"normalized":[{"db_name":"MESH","db_id":"D006402"}]},{"id":"5409","type":"Chemical","text":["ranitidine"],"offsets":[[1377,1387]],"normalized":[{"db_name":"MESH","db_id":"D011899"}]},{"id":"5410","type":"Chemical","text":["creatinine"],"offsets":[[1444,1454]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"5411","type":"Chemical","text":["cimetidine"],"offsets":[[1476,1486]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]},{"id":"5412","type":"Chemical","text":["ranitidine"],"offsets":[[1648,1658]],"normalized":[{"db_name":"MESH","db_id":"D011899"}]},{"id":"5413","type":"Chemical","text":["cimetidine"],"offsets":[[1768,1778]],"normalized":[{"db_name":"MESH","db_id":"D002927"}]}],"events":[],"coreferences":[],"relations":[{"id":"5414","type":"CID","arg1_id":"5388","arg2_id":"5400","normalized":[]},{"id":"5415","type":"CID","arg1_id":"5391","arg2_id":"5400","normalized":[]},{"id":"5416","type":"CID","arg1_id":"5394","arg2_id":"5400","normalized":[]},{"id":"5417","type":"CID","arg1_id":"5397","arg2_id":"5400","normalized":[]},{"id":"5418","type":"CID","arg1_id":"5399","arg2_id":"5400","normalized":[]},{"id":"5419","type":"CID","arg1_id":"5401","arg2_id":"5400","normalized":[]},{"id":"5420","type":"CID","arg1_id":"5402","arg2_id":"5400","normalized":[]},{"id":"5421","type":"CID","arg1_id":"5404","arg2_id":"5400","normalized":[]},{"id":"5422","type":"CID","arg1_id":"5411","arg2_id":"5400","normalized":[]},{"id":"5423","type":"CID","arg1_id":"5413","arg2_id":"5400","normalized":[]}]}
{"id":"5424","document_id":"3670965","passages":[{"id":"5425","type":"title","text":["A catch in the Reye."],"offsets":[[0,20]]},{"id":"5426","type":"abstract","text":["Twenty-six cases of Reye syndrome from The Children's Hospital, Camperdown, Australia, occurring between 1973 and 1982 were reviewed. Of these, 20 cases met the US Public Health Service Centers for Disease Control criteria for the diagnosis of Reye syndrome. Aspirin or salicylate ingestion had occurred in only one of the 20 cases (5%), and paracetamol (acetaminophen) had been administered in only six of the cases (30%). Pathologic confirmation of the diagnosis of Reye syndrome was accomplished in 90% of the cases. The incidence of Reye syndrome in New South Wales, Australia, is estimated from this study to be approximately nine cases per 1 million children compared with recent US data of ten to 20 cases per 1 million children and three to seven cases per 1 million children in Great Britain. The mortality for these Reye syndrome cases in Australia was 45% as compared with a 32% case-fatality rate in the United States. In Australia, the pediatric usage of aspirin has been extremely low for the past 25 years (less than 1% of total dosage units sold), with paracetamol (acetaminophen) dominating the pediatric analgesic and antipyretic market. Reye syndrome may be disappearing from Australia despite a total lack of association with salicylates or aspirin ingestion, since there were no cases found at The Children's Hospital in 1983, 1984, or 1985."],"offsets":[[21,1383]]}],"entities":[{"id":"5427","type":"Disease","text":["Reye"],"offsets":[[15,19]],"normalized":[{"db_name":"MESH","db_id":"D012202"}]},{"id":"5428","type":"Disease","text":["Reye syndrome"],"offsets":[[41,54]],"normalized":[{"db_name":"MESH","db_id":"D012202"}]},{"id":"5429","type":"Disease","text":["Reye syndrome"],"offsets":[[265,278]],"normalized":[{"db_name":"MESH","db_id":"D012202"}]},{"id":"5430","type":"Chemical","text":["Aspirin"],"offsets":[[280,287]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"5431","type":"Chemical","text":["salicylate"],"offsets":[[291,301]],"normalized":[{"db_name":"MESH","db_id":"D012459"}]},{"id":"5432","type":"Chemical","text":["paracetamol"],"offsets":[[363,374]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"5433","type":"Chemical","text":["acetaminophen"],"offsets":[[376,389]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"5434","type":"Disease","text":["Reye syndrome"],"offsets":[[489,502]],"normalized":[{"db_name":"MESH","db_id":"D012202"}]},{"id":"5435","type":"Disease","text":["Reye syndrome"],"offsets":[[558,571]],"normalized":[{"db_name":"MESH","db_id":"D012202"}]},{"id":"5436","type":"Disease","text":["Reye syndrome"],"offsets":[[847,860]],"normalized":[{"db_name":"MESH","db_id":"D012202"}]},{"id":"5437","type":"Chemical","text":["aspirin"],"offsets":[[989,996]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"5438","type":"Chemical","text":["paracetamol"],"offsets":[[1090,1101]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"5439","type":"Chemical","text":["acetaminophen"],"offsets":[[1103,1116]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"5440","type":"Disease","text":["Reye syndrome"],"offsets":[[1177,1190]],"normalized":[{"db_name":"MESH","db_id":"D012202"}]},{"id":"5441","type":"Chemical","text":["salicylates"],"offsets":[[1267,1278]],"normalized":[{"db_name":"MESH","db_id":"D012459"}]},{"id":"5442","type":"Chemical","text":["aspirin"],"offsets":[[1282,1289]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]}],"events":[],"coreferences":[],"relations":[{"id":"5443","type":"CID","arg1_id":"5430","arg2_id":"5427","normalized":[]},{"id":"5444","type":"CID","arg1_id":"5430","arg2_id":"5428","normalized":[]},{"id":"5445","type":"CID","arg1_id":"5430","arg2_id":"5429","normalized":[]},{"id":"5446","type":"CID","arg1_id":"5430","arg2_id":"5434","normalized":[]},{"id":"5447","type":"CID","arg1_id":"5430","arg2_id":"5435","normalized":[]},{"id":"5448","type":"CID","arg1_id":"5430","arg2_id":"5436","normalized":[]},{"id":"5449","type":"CID","arg1_id":"5430","arg2_id":"5440","normalized":[]},{"id":"5450","type":"CID","arg1_id":"5437","arg2_id":"5427","normalized":[]},{"id":"5451","type":"CID","arg1_id":"5437","arg2_id":"5428","normalized":[]},{"id":"5452","type":"CID","arg1_id":"5437","arg2_id":"5429","normalized":[]},{"id":"5453","type":"CID","arg1_id":"5437","arg2_id":"5434","normalized":[]},{"id":"5454","type":"CID","arg1_id":"5437","arg2_id":"5435","normalized":[]},{"id":"5455","type":"CID","arg1_id":"5437","arg2_id":"5436","normalized":[]},{"id":"5456","type":"CID","arg1_id":"5437","arg2_id":"5440","normalized":[]},{"id":"5457","type":"CID","arg1_id":"5442","arg2_id":"5427","normalized":[]},{"id":"5458","type":"CID","arg1_id":"5442","arg2_id":"5428","normalized":[]},{"id":"5459","type":"CID","arg1_id":"5442","arg2_id":"5429","normalized":[]},{"id":"5460","type":"CID","arg1_id":"5442","arg2_id":"5434","normalized":[]},{"id":"5461","type":"CID","arg1_id":"5442","arg2_id":"5435","normalized":[]},{"id":"5462","type":"CID","arg1_id":"5442","arg2_id":"5436","normalized":[]},{"id":"5463","type":"CID","arg1_id":"5442","arg2_id":"5440","normalized":[]}]}
{"id":"5464","document_id":"3300918","passages":[{"id":"5465","type":"title","text":["St. Anthony's fire, then and now: a case report and historical review."],"offsets":[[0,70]]},{"id":"5466","type":"abstract","text":["A rare case of morbid vasospasm, together with striking angiographic findings, is described secondary to the ingestion of methysergide by a 48-year-old woman. A brief review of the literature on similar cases is presented. A discussion of the history of ergot includes its original discovery, the epidemics of gangrene that it has caused through the ages and its past and present role in the management of migraine headache. Despite the advent of calcium channel blockers and beta-adrenergic antagonists, ergot preparations continue to play a major role in migraine therapy, so that the danger of St. Anthony's fire persists."],"offsets":[[71,696]]}],"entities":[{"id":"5467","type":"Disease","text":["St. Anthony's fire"],"offsets":[[0,18]],"normalized":[{"db_name":"MESH","db_id":"D004881"}]},{"id":"5468","type":"Disease","text":["vasospasm"],"offsets":[[93,102]],"normalized":[{"db_name":"MESH","db_id":"D014652"}]},{"id":"5469","type":"Chemical","text":["methysergide"],"offsets":[[193,205]],"normalized":[{"db_name":"MESH","db_id":"D008784"}]},{"id":"5470","type":"Chemical","text":["ergot"],"offsets":[[325,330]],"normalized":[{"db_name":"MESH","db_id":"D004876"}]},{"id":"5471","type":"Disease","text":["gangrene"],"offsets":[[381,389]],"normalized":[{"db_name":"MESH","db_id":"D005734"}]},{"id":"5472","type":"Disease","text":["migraine headache"],"offsets":[[477,494]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"5473","type":"Chemical","text":["calcium"],"offsets":[[518,525]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"5474","type":"Chemical","text":["ergot"],"offsets":[[576,581]],"normalized":[{"db_name":"MESH","db_id":"D004876"}]},{"id":"5475","type":"Disease","text":["migraine"],"offsets":[[628,636]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"5476","type":"Disease","text":["St. Anthony's fire"],"offsets":[[668,686]],"normalized":[{"db_name":"MESH","db_id":"D004881"}]}],"events":[],"coreferences":[],"relations":[{"id":"5477","type":"CID","arg1_id":"5470","arg2_id":"5472","normalized":[]},{"id":"5478","type":"CID","arg1_id":"5470","arg2_id":"5475","normalized":[]},{"id":"5479","type":"CID","arg1_id":"5474","arg2_id":"5472","normalized":[]},{"id":"5480","type":"CID","arg1_id":"5474","arg2_id":"5475","normalized":[]},{"id":"5481","type":"CID","arg1_id":"5469","arg2_id":"5468","normalized":[]}]}
{"id":"5482","document_id":"2826064","passages":[{"id":"5483","type":"title","text":["Beta-2-adrenoceptor-mediated hypokalemia and its abolishment by oxprenolol."],"offsets":[[0,75]]},{"id":"5484","type":"abstract","text":["The time course and concentration-effect relationship of terbutaline-induced hypokalemia was studied, using computer-aided pharmacokinetic-dynamic modeling. Subsequently we investigated the efficacy of oxprenolol in antagonizing such hypokalemia, together with the pharmacokinetic interaction between both drugs. Six healthy subjects were given a 0.5 mg subcutaneous dose of terbutaline on two occasions: 1 hour after oral administration of a placebo and 1 hour after 80 mg oxprenolol orally. In the 7-hour period after terbutaline administration, plasma samples were taken for determination of plasma potassium levels and drug concentrations. The sigmoid Emax model offered a good description of the relation between terbutaline concentrations and potassium effects. Oxprenolol caused decreases of 65% and 56% of terbutaline volume of distribution and clearance, respectively, and an increase of 130% of its AUC. In spite of higher terbutaline concentrations after oxprenolol pretreatment, the hypokalemia was almost completely antagonized by the beta 2-blocking action."],"offsets":[[76,1147]]}],"entities":[{"id":"5485","type":"Disease","text":["hypokalemia"],"offsets":[[29,40]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"5486","type":"Chemical","text":["oxprenolol"],"offsets":[[64,74]],"normalized":[{"db_name":"MESH","db_id":"D010096"}]},{"id":"5487","type":"Chemical","text":["terbutaline"],"offsets":[[133,144]],"normalized":[{"db_name":"MESH","db_id":"D013726"}]},{"id":"5488","type":"Disease","text":["hypokalemia"],"offsets":[[153,164]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"5489","type":"Chemical","text":["oxprenolol"],"offsets":[[278,288]],"normalized":[{"db_name":"MESH","db_id":"D010096"}]},{"id":"5490","type":"Disease","text":["hypokalemia"],"offsets":[[310,321]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"5491","type":"Chemical","text":["terbutaline"],"offsets":[[451,462]],"normalized":[{"db_name":"MESH","db_id":"D013726"}]},{"id":"5492","type":"Chemical","text":["oxprenolol"],"offsets":[[550,560]],"normalized":[{"db_name":"MESH","db_id":"D010096"}]},{"id":"5493","type":"Chemical","text":["terbutaline"],"offsets":[[596,607]],"normalized":[{"db_name":"MESH","db_id":"D013726"}]},{"id":"5494","type":"Chemical","text":["potassium"],"offsets":[[678,687]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"5495","type":"Chemical","text":["terbutaline"],"offsets":[[794,805]],"normalized":[{"db_name":"MESH","db_id":"D013726"}]},{"id":"5496","type":"Chemical","text":["potassium"],"offsets":[[825,834]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"5497","type":"Chemical","text":["Oxprenolol"],"offsets":[[844,854]],"normalized":[{"db_name":"MESH","db_id":"D010096"}]},{"id":"5498","type":"Chemical","text":["terbutaline"],"offsets":[[890,901]],"normalized":[{"db_name":"MESH","db_id":"D013726"}]},{"id":"5499","type":"Chemical","text":["terbutaline"],"offsets":[[1009,1020]],"normalized":[{"db_name":"MESH","db_id":"D013726"}]},{"id":"5500","type":"Chemical","text":["oxprenolol"],"offsets":[[1042,1052]],"normalized":[{"db_name":"MESH","db_id":"D010096"}]},{"id":"5501","type":"Disease","text":["hypokalemia"],"offsets":[[1071,1082]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]}],"events":[],"coreferences":[],"relations":[{"id":"5502","type":"CID","arg1_id":"5487","arg2_id":"5485","normalized":[]},{"id":"5503","type":"CID","arg1_id":"5487","arg2_id":"5488","normalized":[]},{"id":"5504","type":"CID","arg1_id":"5487","arg2_id":"5490","normalized":[]},{"id":"5505","type":"CID","arg1_id":"5487","arg2_id":"5501","normalized":[]},{"id":"5506","type":"CID","arg1_id":"5491","arg2_id":"5485","normalized":[]},{"id":"5507","type":"CID","arg1_id":"5491","arg2_id":"5488","normalized":[]},{"id":"5508","type":"CID","arg1_id":"5491","arg2_id":"5490","normalized":[]},{"id":"5509","type":"CID","arg1_id":"5491","arg2_id":"5501","normalized":[]},{"id":"5510","type":"CID","arg1_id":"5493","arg2_id":"5485","normalized":[]},{"id":"5511","type":"CID","arg1_id":"5493","arg2_id":"5488","normalized":[]},{"id":"5512","type":"CID","arg1_id":"5493","arg2_id":"5490","normalized":[]},{"id":"5513","type":"CID","arg1_id":"5493","arg2_id":"5501","normalized":[]},{"id":"5514","type":"CID","arg1_id":"5495","arg2_id":"5485","normalized":[]},{"id":"5515","type":"CID","arg1_id":"5495","arg2_id":"5488","normalized":[]},{"id":"5516","type":"CID","arg1_id":"5495","arg2_id":"5490","normalized":[]},{"id":"5517","type":"CID","arg1_id":"5495","arg2_id":"5501","normalized":[]},{"id":"5518","type":"CID","arg1_id":"5498","arg2_id":"5485","normalized":[]},{"id":"5519","type":"CID","arg1_id":"5498","arg2_id":"5488","normalized":[]},{"id":"5520","type":"CID","arg1_id":"5498","arg2_id":"5490","normalized":[]},{"id":"5521","type":"CID","arg1_id":"5498","arg2_id":"5501","normalized":[]},{"id":"5522","type":"CID","arg1_id":"5499","arg2_id":"5485","normalized":[]},{"id":"5523","type":"CID","arg1_id":"5499","arg2_id":"5488","normalized":[]},{"id":"5524","type":"CID","arg1_id":"5499","arg2_id":"5490","normalized":[]},{"id":"5525","type":"CID","arg1_id":"5499","arg2_id":"5501","normalized":[]}]}
{"id":"5526","document_id":"2422478","passages":[{"id":"5527","type":"title","text":["Midline B3 serotonin nerves in rat medulla are involved in hypotensive effect of methyldopa."],"offsets":[[0,92]]},{"id":"5528","type":"abstract","text":["Previous experiments in this laboratory have shown that microinjection of methyldopa onto the ventrolateral cells of the B3 serotonin neurons in the medulla elicits a hypotensive response mediated by a projection descending into the spinal cord. The present experiments were designed to investigate the role of the midline cells of the B3 serotonin neurons in the medulla, coinciding with the raphe magnus. In spontaneously hypertensive, stroke-prone rats, microinjection of methyldopa into the area of the midline B3 serotonin cell group in the ventral medulla caused a potent hypotension of 30-40 mm Hg, which was maximal 2-3 h after administration and was abolished by the serotonin neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) injected intracerebroventricularly. However, intraspinal injection of 5,7-DHT to produce a more selective lesion of only descending serotonin projections in the spinal cord did not affect this hypotension. Further, 5,7-DHT lesion of serotonin nerves travelling in the median forebrain bundle, one of the main ascending pathways from the B3 serotonin cells, did not affect the fall in blood pressure associated with a midline B3 serotonin methyldopa injection. It is concluded therefore that, unlike the ventrolateral B3 cells which mediate a methyldopa-induced hypotension via descending projections, the midline serotonin B3 cells in the medulla contribute to the hypotensive action of methyldopa, either by way of an ascending projection which does not pass through the median forebrain bundle, or through a projection restricted to the caudal brainstem."],"offsets":[[93,1680]]}],"entities":[{"id":"5529","type":"Chemical","text":["serotonin"],"offsets":[[11,20]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"5530","type":"Disease","text":["hypotensive"],"offsets":[[59,70]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"5531","type":"Chemical","text":["methyldopa"],"offsets":[[81,91]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]},{"id":"5532","type":"Chemical","text":["methyldopa"],"offsets":[[167,177]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]},{"id":"5533","type":"Chemical","text":["serotonin"],"offsets":[[217,226]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"5534","type":"Disease","text":["hypotensive"],"offsets":[[260,271]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"5535","type":"Chemical","text":["serotonin"],"offsets":[[432,441]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"5536","type":"Disease","text":["hypertensive"],"offsets":[[517,529]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"5537","type":"Disease","text":["stroke"],"offsets":[[531,537]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"5538","type":"Chemical","text":["methyldopa"],"offsets":[[568,578]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]},{"id":"5539","type":"Chemical","text":["serotonin"],"offsets":[[611,620]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"5540","type":"Disease","text":["hypotension"],"offsets":[[671,682]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"5541","type":"Chemical","text":["serotonin"],"offsets":[[769,778]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"5542","type":"Chemical","text":["5,7-dihydroxytryptamine"],"offsets":[[790,813]],"normalized":[{"db_name":"MESH","db_id":"D015116"}]},{"id":"5543","type":"Chemical","text":["5,7-DHT"],"offsets":[[815,822]],"normalized":[{"db_name":"MESH","db_id":"D015116"}]},{"id":"5544","type":"Chemical","text":["5,7-DHT"],"offsets":[[894,901]],"normalized":[{"db_name":"MESH","db_id":"D015116"}]},{"id":"5545","type":"Chemical","text":["serotonin"],"offsets":[[956,965]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"5546","type":"Disease","text":["hypotension"],"offsets":[[1017,1028]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"5547","type":"Chemical","text":["5,7-DHT"],"offsets":[[1039,1046]],"normalized":[{"db_name":"MESH","db_id":"D015116"}]},{"id":"5548","type":"Chemical","text":["serotonin"],"offsets":[[1057,1066]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"5549","type":"Chemical","text":["serotonin"],"offsets":[[1164,1173]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"5550","type":"Chemical","text":["serotonin"],"offsets":[[1252,1261]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"5551","type":"Chemical","text":["methyldopa"],"offsets":[[1262,1272]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]},{"id":"5552","type":"Chemical","text":["methyldopa"],"offsets":[[1366,1376]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]},{"id":"5553","type":"Disease","text":["hypotension"],"offsets":[[1385,1396]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"5554","type":"Chemical","text":["serotonin"],"offsets":[[1437,1446]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"5555","type":"Disease","text":["hypotensive"],"offsets":[[1489,1500]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"5556","type":"Chemical","text":["methyldopa"],"offsets":[[1511,1521]],"normalized":[{"db_name":"MESH","db_id":"D008750"}]}],"events":[],"coreferences":[],"relations":[{"id":"5557","type":"CID","arg1_id":"5531","arg2_id":"5530","normalized":[]},{"id":"5558","type":"CID","arg1_id":"5531","arg2_id":"5534","normalized":[]},{"id":"5559","type":"CID","arg1_id":"5531","arg2_id":"5540","normalized":[]},{"id":"5560","type":"CID","arg1_id":"5531","arg2_id":"5546","normalized":[]},{"id":"5561","type":"CID","arg1_id":"5531","arg2_id":"5553","normalized":[]},{"id":"5562","type":"CID","arg1_id":"5531","arg2_id":"5555","normalized":[]},{"id":"5563","type":"CID","arg1_id":"5532","arg2_id":"5530","normalized":[]},{"id":"5564","type":"CID","arg1_id":"5532","arg2_id":"5534","normalized":[]},{"id":"5565","type":"CID","arg1_id":"5532","arg2_id":"5540","normalized":[]},{"id":"5566","type":"CID","arg1_id":"5532","arg2_id":"5546","normalized":[]},{"id":"5567","type":"CID","arg1_id":"5532","arg2_id":"5553","normalized":[]},{"id":"5568","type":"CID","arg1_id":"5532","arg2_id":"5555","normalized":[]},{"id":"5569","type":"CID","arg1_id":"5538","arg2_id":"5530","normalized":[]},{"id":"5570","type":"CID","arg1_id":"5538","arg2_id":"5534","normalized":[]},{"id":"5571","type":"CID","arg1_id":"5538","arg2_id":"5540","normalized":[]},{"id":"5572","type":"CID","arg1_id":"5538","arg2_id":"5546","normalized":[]},{"id":"5573","type":"CID","arg1_id":"5538","arg2_id":"5553","normalized":[]},{"id":"5574","type":"CID","arg1_id":"5538","arg2_id":"5555","normalized":[]},{"id":"5575","type":"CID","arg1_id":"5551","arg2_id":"5530","normalized":[]},{"id":"5576","type":"CID","arg1_id":"5551","arg2_id":"5534","normalized":[]},{"id":"5577","type":"CID","arg1_id":"5551","arg2_id":"5540","normalized":[]},{"id":"5578","type":"CID","arg1_id":"5551","arg2_id":"5546","normalized":[]},{"id":"5579","type":"CID","arg1_id":"5551","arg2_id":"5553","normalized":[]},{"id":"5580","type":"CID","arg1_id":"5551","arg2_id":"5555","normalized":[]},{"id":"5581","type":"CID","arg1_id":"5552","arg2_id":"5530","normalized":[]},{"id":"5582","type":"CID","arg1_id":"5552","arg2_id":"5534","normalized":[]},{"id":"5583","type":"CID","arg1_id":"5552","arg2_id":"5540","normalized":[]},{"id":"5584","type":"CID","arg1_id":"5552","arg2_id":"5546","normalized":[]},{"id":"5585","type":"CID","arg1_id":"5552","arg2_id":"5553","normalized":[]},{"id":"5586","type":"CID","arg1_id":"5552","arg2_id":"5555","normalized":[]},{"id":"5587","type":"CID","arg1_id":"5556","arg2_id":"5530","normalized":[]},{"id":"5588","type":"CID","arg1_id":"5556","arg2_id":"5534","normalized":[]},{"id":"5589","type":"CID","arg1_id":"5556","arg2_id":"5540","normalized":[]},{"id":"5590","type":"CID","arg1_id":"5556","arg2_id":"5546","normalized":[]},{"id":"5591","type":"CID","arg1_id":"5556","arg2_id":"5553","normalized":[]},{"id":"5592","type":"CID","arg1_id":"5556","arg2_id":"5555","normalized":[]}]}
{"id":"5593","document_id":"1535072","passages":[{"id":"5594","type":"title","text":["Yohimbine treatment of sexual side effects induced by serotonin reuptake blockers."],"offsets":[[0,82]]},{"id":"5595","type":"abstract","text":["BACKGROUND: Preclinical and clinical studies suggest that yohimbine facilitates sexual behavior and may be helpful in the treatment of male impotence. A single case report suggests that yohimbine may be used to treat the sexual side effects of clomipramine. This study evaluated yohimbine as a treatment for the sexual side effects caused by serotonin reuptake blockers. METHOD: Six patients with either obsessive compulsive disorder, trichotillomania, anxiety, or affective disorders who suffered sexual side effects after treatment with serotonin reuptake blockers were given yohimbine on a p.r.n. basis in an open clinical trial. Various doses of yohimbine were used to determine the ideal dose for each patient. RESULTS: Five of the six patients experienced improved sexual functioning after taking yohimbine. One patient who failed to comply with yohimbine treatment had no therapeutic effects. Side effects of yohimbine included excessive sweating, increased anxiety, and a wound-up feeling in some patients. CONCLUSION: The results of this study indicate that yohimbine may be an effective treatment for the sexual side effects caused by serotonin reuptake blockers. Future controlled studies are needed to further investigate the effectiveness and safety of yohimbine for this indication."],"offsets":[[83,1379]]}],"entities":[{"id":"5596","type":"Chemical","text":["Yohimbine"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D015016"}]},{"id":"5597","type":"Disease","text":["sexual side effects"],"offsets":[[23,42]],"normalized":[{"db_name":"MESH","db_id":"D020018"}]},{"id":"5598","type":"Chemical","text":["serotonin"],"offsets":[[54,63]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"5599","type":"Chemical","text":["yohimbine"],"offsets":[[141,150]],"normalized":[{"db_name":"MESH","db_id":"D015016"}]},{"id":"5600","type":"Disease","text":["male impotence"],"offsets":[[218,232]],"normalized":[{"db_name":"MESH","db_id":"D007172"}]},{"id":"5601","type":"Chemical","text":["yohimbine"],"offsets":[[269,278]],"normalized":[{"db_name":"MESH","db_id":"D015016"}]},{"id":"5602","type":"Disease","text":["sexual side effects"],"offsets":[[304,323]],"normalized":[{"db_name":"MESH","db_id":"D020018"}]},{"id":"5603","type":"Chemical","text":["clomipramine"],"offsets":[[327,339]],"normalized":[{"db_name":"MESH","db_id":"D002997"}]},{"id":"5604","type":"Chemical","text":["yohimbine"],"offsets":[[362,371]],"normalized":[{"db_name":"MESH","db_id":"D015016"}]},{"id":"5605","type":"Disease","text":["sexual side effects"],"offsets":[[395,414]],"normalized":[{"db_name":"MESH","db_id":"D020018"}]},{"id":"5606","type":"Chemical","text":["serotonin"],"offsets":[[425,434]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"5607","type":"Disease","text":["obsessive compulsive disorder"],"offsets":[[487,516]],"normalized":[{"db_name":"MESH","db_id":"D009771"}]},{"id":"5608","type":"Disease","text":["trichotillomania"],"offsets":[[518,534]],"normalized":[{"db_name":"MESH","db_id":"D014256"}]},{"id":"5609","type":"Disease","text":["anxiety"],"offsets":[[536,543]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"5610","type":"Disease","text":["affective disorders"],"offsets":[[548,567]],"normalized":[{"db_name":"MESH","db_id":"D019964"}]},{"id":"5611","type":"Disease","text":["sexual side effects"],"offsets":[[581,600]],"normalized":[{"db_name":"MESH","db_id":"D020018"}]},{"id":"5612","type":"Chemical","text":["serotonin"],"offsets":[[622,631]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"5613","type":"Chemical","text":["yohimbine"],"offsets":[[661,670]],"normalized":[{"db_name":"MESH","db_id":"D015016"}]},{"id":"5614","type":"Chemical","text":["yohimbine"],"offsets":[[733,742]],"normalized":[{"db_name":"MESH","db_id":"D015016"}]},{"id":"5615","type":"Chemical","text":["yohimbine"],"offsets":[[886,895]],"normalized":[{"db_name":"MESH","db_id":"D015016"}]},{"id":"5616","type":"Chemical","text":["yohimbine"],"offsets":[[935,944]],"normalized":[{"db_name":"MESH","db_id":"D015016"}]},{"id":"5617","type":"Chemical","text":["yohimbine"],"offsets":[[999,1008]],"normalized":[{"db_name":"MESH","db_id":"D015016"}]},{"id":"5618","type":"Disease","text":["anxiety"],"offsets":[[1048,1055]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"5619","type":"Chemical","text":["yohimbine"],"offsets":[[1150,1159]],"normalized":[{"db_name":"MESH","db_id":"D015016"}]},{"id":"5620","type":"Disease","text":["sexual side effects"],"offsets":[[1198,1217]],"normalized":[{"db_name":"MESH","db_id":"D020018"}]},{"id":"5621","type":"Chemical","text":["serotonin"],"offsets":[[1228,1237]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"5622","type":"Chemical","text":["yohimbine"],"offsets":[[1349,1358]],"normalized":[{"db_name":"MESH","db_id":"D015016"}]}],"events":[],"coreferences":[],"relations":[{"id":"5623","type":"CID","arg1_id":"5603","arg2_id":"5597","normalized":[]},{"id":"5624","type":"CID","arg1_id":"5603","arg2_id":"5602","normalized":[]},{"id":"5625","type":"CID","arg1_id":"5603","arg2_id":"5605","normalized":[]},{"id":"5626","type":"CID","arg1_id":"5603","arg2_id":"5611","normalized":[]},{"id":"5627","type":"CID","arg1_id":"5603","arg2_id":"5620","normalized":[]}]}
{"id":"5628","document_id":"1504402","passages":[{"id":"5629","type":"title","text":["Hypersensitivity immune reaction as a mechanism for dilevalol-associated hepatitis."],"offsets":[[0,83]]},{"id":"5630","type":"abstract","text":["OBJECTIVE: To assess lymphocyte reactivity to dilevalol and to serum containing putative ex vivo dilevalol antigens or metabolites in a case of dilevalol-induced liver injury. PATIENT: A 58-year-old woman with a clinical diagnosis of dilevalol-induced liver injury. METHODS: Peripheral blood mononuclear cells collected from the patient were cultured in the presence of a solution of dilevalol and also with sera collected from a volunteer before and after dilevalol intake. A similar protocol was performed with lymphocytes from a healthy subject. RESULTS: No lymphocyte proliferation was observed either in the patient or in the healthy volunteer in the presence of dilevalol solutions. A significant proliferative response to serum collected after dilevalol intake was observed in the case of the patient compared with the proliferative response to the serum collected before the drug intake. No reactivity was found when lymphocytes from the healthy subject were tested under similar conditions. CONCLUSIONS: The methodology used allowed the detection of lymphocyte sensitization to sera containing ex vivo-prepared dilevalol antigens, suggesting the involvement of an immunologic mechanism in dilevalol-induced liver injury."],"offsets":[[84,1313]]}],"entities":[{"id":"5631","type":"Disease","text":["Hypersensitivity"],"offsets":[[0,16]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"5632","type":"Chemical","text":["dilevalol"],"offsets":[[52,61]],"normalized":[{"db_name":"MESH","db_id":"D007741"}]},{"id":"5633","type":"Disease","text":["hepatitis"],"offsets":[[73,82]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"5634","type":"Chemical","text":["dilevalol"],"offsets":[[130,139]],"normalized":[{"db_name":"MESH","db_id":"D007741"}]},{"id":"5635","type":"Chemical","text":["dilevalol"],"offsets":[[181,190]],"normalized":[{"db_name":"MESH","db_id":"D007741"}]},{"id":"5636","type":"Chemical","text":["dilevalol"],"offsets":[[228,237]],"normalized":[{"db_name":"MESH","db_id":"D007741"}]},{"id":"5637","type":"Disease","text":["liver 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injury"],"offsets":[[336,348]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"5640","type":"Chemical","text":["dilevalol"],"offsets":[[468,477]],"normalized":[{"db_name":"MESH","db_id":"D007741"}]},{"id":"5641","type":"Chemical","text":["dilevalol"],"offsets":[[541,550]],"normalized":[{"db_name":"MESH","db_id":"D007741"}]},{"id":"5642","type":"Chemical","text":["dilevalol"],"offsets":[[752,761]],"normalized":[{"db_name":"MESH","db_id":"D007741"}]},{"id":"5643","type":"Chemical","text":["dilevalol"],"offsets":[[835,844]],"normalized":[{"db_name":"MESH","db_id":"D007741"}]},{"id":"5644","type":"Chemical","text":["dilevalol"],"offsets":[[1204,1213]],"normalized":[{"db_name":"MESH","db_id":"D007741"}]},{"id":"5645","type":"Chemical","text":["dilevalol"],"offsets":[[1282,1291]],"normalized":[{"db_name":"MESH","db_id":"D007741"}]},{"id":"5646","type":"Disease","text":["liver 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{"id":"5702","document_id":"19917396","passages":[{"id":"5703","type":"title","text":["Reversible myocardial hypertrophy induced by tacrolimus in a pediatric heart transplant recipient: case report."],"offsets":[[0,111]]},{"id":"5704","type":"abstract","text":["Tacrolimus is a potent immunosuppressant that is frequently used in organ transplantation. However, adverse effects include cardiac toxicity. Herein we describe transient myocardial hypertrophy induced by tacrolimus after heart transplantation. The hypertrophy caused no clinical symptoms but was noted because of elevation of plasma brain natriuretic peptide concentration and confirmed at echocardiography. Initially, allograft rejection was feared; however, myocardial biopsy samples revealed only interstitial edema and mild myocardial hypertrophy; neither cellular nor humoral rejection was detected. The blood tacrolimus concentration was higher than usual at that time; thus, tacrolimus dosage was reduced. Myocardial hypertrophy completely resolved upon reducing the target concentration of tacrolimus and did not recur, as confirmed at echocardiography and myocardial biopsy. Thus, we conclude that tacrolimus induces reversible myocardial hypertrophy. In patients receiving tacrolimus therapy, blood concentration should be carefully controlled and extreme attention paid to cardiac involvement."],"offsets":[[112,1217]]}],"entities":[{"id":"5705","type":"Disease","text":["myocardial hypertrophy"],"offsets":[[11,33]],"normalized":[{"db_name":"MESH","db_id":"D006332"}]},{"id":"5706","type":"Chemical","text":["tacrolimus"],"offsets":[[45,55]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"5707","type":"Chemical","text":["Tacrolimus"],"offsets":[[112,122]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"5708","type":"Disease","text":["cardiac toxicity"],"offsets":[[236,252]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"5709","type":"Disease","text":["myocardial 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hypertrophy"],"offsets":[[826,848]],"normalized":[{"db_name":"MESH","db_id":"D006332"}]},{"id":"5717","type":"Chemical","text":["tacrolimus"],"offsets":[[911,921]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"5718","type":"Chemical","text":["tacrolimus"],"offsets":[[1020,1030]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"5719","type":"Disease","text":["myocardial 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{"id":"5761","document_id":"19234905","passages":[{"id":"5762","type":"title","text":["Comparison of unilateral pallidotomy and subthalamotomy findings in advanced idiopathic Parkinson's disease."],"offsets":[[0,108]]},{"id":"5763","type":"abstract","text":["A prospective, randomized, double-blind pilot study to compare the results of stereotactic unilateral pallidotomy and subthalamotomy in advanced idiopathic Parkinson's disease (PD) refractory to medical treatment was designed. Ten consecutive patients (mean age, 58.4 +\/- 6.8 years; 7 men, 3 women) with similar characteristics at the duration of disease (mean disease time, 8.4 +\/- 3.5 years), disabling motor fluctuations (Hoehn _ Yahr stage 3-5 in off-drug phases) and levodopa-induced dyskinesias were selected. All patients had bilateral symptoms and their levodopa equivalent dosing were analysed. Six patients were operated on in the globus pallidus interna (GPi) and four in the subthalamic nucleus (STN). Clinical evaluation included the use of the Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn_Yahr score and Schwab England activities of daily living (ADL) score in 'on'- and 'off'-drug conditions before surgery and 6 months after surgery. There was statistically significant improvement in all contralateral major parkinsonian motor signs in all patients followed for 6 months. Levodopa equivalent daily intake was significantly reduced in the STN group. Changes in UPDRS, Hoehn _ Yahr and Schwab England ADL scores were similar in both groups. Cognitive functions were unchanged in both groups. Complications were observed in two patients: one had a left homonymous hemianopsia after pallidotomy and another one developed left hemiballistic movements 3 days after subthalamotomy which partly improved within 1 month with Valproate 1000 mg\/day. The findings of this study suggest that lesions of the unilateral STN and GPi are equally effective treatment for patients with advanced PD refractory to medical treatment."],"offsets":[[109,1848]]}],"entities":[{"id":"5764","type":"Disease","text":["idiopathic Parkinson's disease"],"offsets":[[77,107]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"5765","type":"Disease","text":["idiopathic Parkinson's disease"],"offsets":[[254,284]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"5766","type":"Disease","text":["PD"],"offsets":[[286,288]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"5767","type":"Chemical","text":["levodopa"],"offsets":[[581,589]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"5768","type":"Disease","text":["dyskinesias"],"offsets":[[598,609]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"5769","type":"Chemical","text":["levodopa"],"offsets":[[671,679]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"5770","type":"Disease","text":["Parkinson's Disease"],"offsets":[[875,894]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"5771","type":"Disease","text":["parkinsonian"],"offsets":[[1145,1157]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"5772","type":"Chemical","text":["Levodopa"],"offsets":[[1209,1217]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"5773","type":"Disease","text":["homonymous hemianopsia"],"offsets":[[1487,1509]],"normalized":[{"db_name":"MESH","db_id":"D006423"}]},{"id":"5774","type":"Chemical","text":["Valproate"],"offsets":[[1653,1662]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"5775","type":"Disease","text":["PD"],"offsets":[[1813,1815]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]}],"events":[],"coreferences":[],"relations":[{"id":"5776","type":"CID","arg1_id":"5767","arg2_id":"5768","normalized":[]},{"id":"5777","type":"CID","arg1_id":"5769","arg2_id":"5768","normalized":[]},{"id":"5778","type":"CID","arg1_id":"5772","arg2_id":"5768","normalized":[]}]}
{"id":"5779","document_id":"18541230","passages":[{"id":"5780","type":"title","text":["Protective effects of antithrombin on puromycin aminonucleoside nephrosis in rats."],"offsets":[[0,82]]},{"id":"5781","type":"abstract","text":["We investigated the effects of antithrombin, a plasma inhibitor of coagulation factors, in rats with puromycin aminonucleoside-induced nephrosis, which is an experimental model of human nephrotic syndrome. Antithrombin (50 or 500 IU\/kg\/i.v.) was administered to rats once a day for 10 days immediately after the injection of puromycin aminonucleoside (50 mg\/kg\/i.v.). Treatment with antithrombin attenuated the puromycin aminonucleoside-induced hematological abnormalities. Puromycin aminonucleoside-induced renal dysfunction and hyperlipidemia were also suppressed. Histopathological examination revealed severe renal damage such as proteinaceous casts in tubuli and tubular expansion in the kidney of control rats, while an improvement of the damage was seen in antithrombin-treated rats. In addition, antithrombin treatment markedly suppressed puromycin aminonucleoside-induced apoptosis of renal tubular epithelial cells. Furthermore, puromycin aminonucleoside-induced increases in renal cytokine content were also decreased. These findings suggest that thrombin plays an important role in the pathogenesis of puromycin aminonucleoside-induced nephrotic syndrome. Treatment with antithrombin may be clinically effective in patients with nephrotic syndrome."],"offsets":[[83,1343]]}],"entities":[{"id":"5782","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[38,63]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"5783","type":"Disease","text":["nephrosis"],"offsets":[[64,73]],"normalized":[{"db_name":"MESH","db_id":"D009401"}]},{"id":"5784","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[184,209]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"5785","type":"Disease","text":["nephrosis"],"offsets":[[218,227]],"normalized":[{"db_name":"MESH","db_id":"D009401"}]},{"id":"5786","type":"Disease","text":["nephrotic syndrome"],"offsets":[[269,287]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]},{"id":"5787","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[408,433]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"5788","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[494,519]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"5789","type":"Disease","text":["hematological abnormalities"],"offsets":[[528,555]],"normalized":[{"db_name":"MESH","db_id":"D006402"}]},{"id":"5790","type":"Chemical","text":["Puromycin aminonucleoside"],"offsets":[[557,582]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"5791","type":"Disease","text":["renal dysfunction"],"offsets":[[591,608]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"5792","type":"Disease","text":["hyperlipidemia"],"offsets":[[613,627]],"normalized":[{"db_name":"MESH","db_id":"D006949"}]},{"id":"5793","type":"Disease","text":["renal damage"],"offsets":[[696,708]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"5794","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[930,955]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"5795","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[1022,1047]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"5796","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[1197,1222]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"5797","type":"Disease","text":["nephrotic syndrome"],"offsets":[[1231,1249]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]},{"id":"5798","type":"Disease","text":["nephrotic syndrome"],"offsets":[[1324,1342]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]}],"events":[],"coreferences":[],"relations":[{"id":"5799","type":"CID","arg1_id":"5782","arg2_id":"5783","normalized":[]},{"id":"5800","type":"CID","arg1_id":"5782","arg2_id":"5785","normalized":[]},{"id":"5801","type":"CID","arg1_id":"5784","arg2_id":"5783","normalized":[]},{"id":"5802","type":"CID","arg1_id":"5784","arg2_id":"5785","normalized":[]},{"id":"5803","type":"CID","arg1_id":"5787","arg2_id":"5783","normalized":[]},{"id":"5804","type":"CID","arg1_id":"5787","arg2_id":"5785","normalized":[]},{"id":"5805","type":"CID","arg1_id":"5788","arg2_id":"5783","normalized":[]},{"id":"5806","type":"CID","arg1_id":"5788","arg2_id":"5785","normalized":[]},{"id":"5807","type":"CID","arg1_id":"5790","arg2_id":"5783","normalized":[]},{"id":"5808","type":"CID","arg1_id":"5790","arg2_id":"5785","normalized":[]},{"id":"5809","type":"CID","arg1_id":"5794","arg2_id":"5783","normalized":[]},{"id":"5810","type":"CID","arg1_id":"5794","arg2_id":"5785","normalized":[]},{"id":"5811","type":"CID","arg1_id":"5795","arg2_id":"5783","normalized":[]},{"id":"5812","type":"CID","arg1_id":"5795","arg2_id":"5785","normalized":[]},{"id":"5813","type":"CID","arg1_id":"5796","arg2_id":"5783","normalized":[]},{"id":"5814","type":"CID","arg1_id":"5796","arg2_id":"5785","normalized":[]}]}
{"id":"5815","document_id":"18177388","passages":[{"id":"5816","type":"title","text":["Reverse or inverted left ventricular apical ballooning syndrome (reverse Takotsubo cardiomyopathy) in a young woman in the setting of amphetamine use."],"offsets":[[0,150]]},{"id":"5817","type":"abstract","text":["Transient left ventricular apical ballooning syndrome was first described in Japan as \"Takotsubo cardiomyopathy.\" This syndrome has been identified in many other countries. Many variations of this syndrome have been recently described in the literature. One of the rarest is the reverse type of this syndrome, with hyperdynamic apex and complete akinesia of the base (as opposed to the classic apical ballooning). In this article, we report an interesting case of a young woman who presented with this rare type of reverse apical ballooning syndrome occurring after amphetamine use. This report is followed by review of the literature."],"offsets":[[151,786]]}],"entities":[{"id":"5818","type":"Disease","text":["left ventricular apical ballooning syndrome"],"offsets":[[20,63]],"normalized":[{"db_name":"MESH","db_id":"D054549"}]},{"id":"5819","type":"Disease","text":["Takotsubo cardiomyopathy"],"offsets":[[73,97]],"normalized":[{"db_name":"MESH","db_id":"D054549"}]},{"id":"5820","type":"Chemical","text":["amphetamine"],"offsets":[[134,145]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"5821","type":"Disease","text":["left ventricular apical ballooning syndrome"],"offsets":[[161,204]],"normalized":[{"db_name":"MESH","db_id":"D054549"}]},{"id":"5822","type":"Disease","text":["Takotsubo cardiomyopathy"],"offsets":[[238,262]],"normalized":[{"db_name":"MESH","db_id":"D054549"}]},{"id":"5823","type":"Disease","text":["akinesia"],"offsets":[[497,505]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"5824","type":"Disease","text":["apical ballooning"],"offsets":[[545,562]],"normalized":[{"db_name":"MESH","db_id":"D054549"}]},{"id":"5825","type":"Disease","text":["apical ballooning syndrome"],"offsets":[[674,700]],"normalized":[{"db_name":"MESH","db_id":"D054549"}]},{"id":"5826","type":"Chemical","text":["amphetamine"],"offsets":[[717,728]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]}],"events":[],"coreferences":[],"relations":[{"id":"5827","type":"CID","arg1_id":"5820","arg2_id":"5818","normalized":[]},{"id":"5828","type":"CID","arg1_id":"5820","arg2_id":"5819","normalized":[]},{"id":"5829","type":"CID","arg1_id":"5820","arg2_id":"5821","normalized":[]},{"id":"5830","type":"CID","arg1_id":"5820","arg2_id":"5822","normalized":[]},{"id":"5831","type":"CID","arg1_id":"5820","arg2_id":"5824","normalized":[]},{"id":"5832","type":"CID","arg1_id":"5820","arg2_id":"5825","normalized":[]},{"id":"5833","type":"CID","arg1_id":"5826","arg2_id":"5818","normalized":[]},{"id":"5834","type":"CID","arg1_id":"5826","arg2_id":"5819","normalized":[]},{"id":"5835","type":"CID","arg1_id":"5826","arg2_id":"5821","normalized":[]},{"id":"5836","type":"CID","arg1_id":"5826","arg2_id":"5822","normalized":[]},{"id":"5837","type":"CID","arg1_id":"5826","arg2_id":"5824","normalized":[]},{"id":"5838","type":"CID","arg1_id":"5826","arg2_id":"5825","normalized":[]}]}
{"id":"5839","document_id":"17490864","passages":[{"id":"5840","type":"title","text":["Attenuated disruption of prepulse inhibition by dopaminergic stimulation after maternal deprivation and adolescent corticosterone treatment in rats."],"offsets":[[0,148]]},{"id":"5841","type":"abstract","text":["The development of schizophrenia may include an early neurodevelopmental stress component which increases vulnerability to later stressful life events, in combination leading to overt disease. We investigated the effect of an early stress, in the form of maternal deprivation, combined with a later stress, simulated by chronic periadolescent corticosterone treatment, on behaviour in rats. Acute treatment with apomorphine caused disruption of prepulse inhibition (PPI) in controls and in rats that had undergone either maternal deprivation or corticosterone treatment, but was surprisingly absent in rats that had undergone the combined early and late stress. Amphetamine treatment significantly disrupted PPI in both non-deprived groups, but was absent in both maternally deprived groups. The serotonin-1A receptor agonist, 8-OH-DPAT, induced a significant disruption of PPI in all groups. Amphetamine-induced locomotor hyperactivity was similar in all groups. These results show an inhibitory interaction of early stress, caused by maternal deprivation, combined with 'adolescent' stress, simulated by corticosterone treatment, on dopaminergic regulation of PPI. The altered effects of apomorphine and amphetamine could indicate differential changes in dopamine receptor signalling leading to functional desensitisation, or altered modulation of sensory gating in the nucleus accumbens by limbic structures such as the hippocampus."],"offsets":[[149,1584]]}],"entities":[{"id":"5842","type":"Chemical","text":["corticosterone"],"offsets":[[115,129]],"normalized":[{"db_name":"MESH","db_id":"D003345"}]},{"id":"5843","type":"Disease","text":["schizophrenia"],"offsets":[[168,181]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"5844","type":"Chemical","text":["corticosterone"],"offsets":[[492,506]],"normalized":[{"db_name":"MESH","db_id":"D003345"}]},{"id":"5845","type":"Chemical","text":["apomorphine"],"offsets":[[561,572]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"5846","type":"Chemical","text":["corticosterone"],"offsets":[[694,708]],"normalized":[{"db_name":"MESH","db_id":"D003345"}]},{"id":"5847","type":"Chemical","text":["Amphetamine"],"offsets":[[811,822]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"5848","type":"Chemical","text":["serotonin"],"offsets":[[945,954]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"5849","type":"Chemical","text":["8-OH-DPAT"],"offsets":[[976,985]],"normalized":[{"db_name":"MESH","db_id":"D017371"}]},{"id":"5850","type":"Chemical","text":["Amphetamine"],"offsets":[[1042,1053]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"5851","type":"Disease","text":["locomotor hyperactivity"],"offsets":[[1062,1085]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"5852","type":"Chemical","text":["corticosterone"],"offsets":[[1255,1269]],"normalized":[{"db_name":"MESH","db_id":"D003345"}]},{"id":"5853","type":"Chemical","text":["apomorphine"],"offsets":[[1339,1350]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"5854","type":"Chemical","text":["amphetamine"],"offsets":[[1355,1366]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"5855","type":"Chemical","text":["dopamine"],"offsets":[[1406,1414]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]}],"events":[],"coreferences":[],"relations":[{"id":"5856","type":"CID","arg1_id":"5847","arg2_id":"5851","normalized":[]},{"id":"5857","type":"CID","arg1_id":"5850","arg2_id":"5851","normalized":[]},{"id":"5858","type":"CID","arg1_id":"5854","arg2_id":"5851","normalized":[]}]}
{"id":"5859","document_id":"17490790","passages":[{"id":"5860","type":"title","text":["Peripheral iron dextran induced degeneration of dopaminergic neurons in rat substantia nigra."],"offsets":[[0,93]]},{"id":"5861","type":"abstract","text":["Iron accumulation is considered to be involved in the pathogenesis of Parkinson's disease. To demonstrate the relationship between peripheral iron overload and dopaminergic neuron loss in rat substantia nigra (SN), in the present study we used fast cyclic voltammetry, tyrosine hydroxylase (TH) immunohistochemistry, Perls' iron staining, and high performance liquid chromatography-electrochemical detection to study the degeneration of dopaminergic neurons and increased iron content in the SN of iron dextran overloaded animals. The findings showed that peripheral iron dextran overload increased the iron staining positive cells and reduced the number of TH-immunoreactive neurons in the SN. As a result, dopamine release and content, as well as its metabolites contents were decreased in caudate putamen. Even more dramatic changes were found in chronic overload group. These results suggest that peripheral iron dextran can increase the iron level in the SN, where excessive iron causes the degeneration of dopaminergic neurons. The chronic iron overload may be more destructive to dopaminergic neurons than the acute iron overload."],"offsets":[[94,1231]]}],"entities":[{"id":"5862","type":"Chemical","text":["iron dextran"],"offsets":[[11,23]],"normalized":[{"db_name":"MESH","db_id":"D007505"}]},{"id":"5863","type":"Disease","text":["degeneration of dopaminergic neurons"],"offsets":[[32,68]],"normalized":[{"db_name":"MESH","db_id":"D009410"}]},{"id":"5864","type":"Chemical","text":["Iron"],"offsets":[[94,98]],"normalized":[{"db_name":"MESH","db_id":"D007501"}]},{"id":"5865","type":"Disease","text":["Parkinson's disease"],"offsets":[[164,183]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"5866","type":"Chemical","text":["iron"],"offsets":[[236,240]],"normalized":[{"db_name":"MESH","db_id":"D007501"}]},{"id":"5867","type":"Chemical","text":["tyrosine"],"offsets":[[363,371]],"normalized":[{"db_name":"MESH","db_id":"D014443"}]},{"id":"5868","type":"Chemical","text":["iron"],"offsets":[[418,422]],"normalized":[{"db_name":"MESH","db_id":"D007501"}]},{"id":"5869","type":"Disease","text":["degeneration of dopaminergic neurons"],"offsets":[[515,551]],"normalized":[{"db_name":"MESH","db_id":"D009410"}]},{"id":"5870","type":"Chemical","text":["iron"],"offsets":[[566,570]],"normalized":[{"db_name":"MESH","db_id":"D007501"}]},{"id":"5871","type":"Chemical","text":["iron dextran"],"offsets":[[592,604]],"normalized":[{"db_name":"MESH","db_id":"D007505"}]},{"id":"5872","type":"Chemical","text":["iron dextran"],"offsets":[[661,673]],"normalized":[{"db_name":"MESH","db_id":"D007505"}]},{"id":"5873","type":"Chemical","text":["iron"],"offsets":[[697,701]],"normalized":[{"db_name":"MESH","db_id":"D007501"}]},{"id":"5874","type":"Chemical","text":["dopamine"],"offsets":[[802,810]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"5875","type":"Chemical","text":["iron dextran"],"offsets":[[1006,1018]],"normalized":[{"db_name":"MESH","db_id":"D007505"}]},{"id":"5876","type":"Chemical","text":["iron"],"offsets":[[1036,1040]],"normalized":[{"db_name":"MESH","db_id":"D007501"}]},{"id":"5877","type":"Chemical","text":["iron"],"offsets":[[1074,1078]],"normalized":[{"db_name":"MESH","db_id":"D007501"}]},{"id":"5878","type":"Disease","text":["degeneration of dopaminergic neurons"],"offsets":[[1090,1126]],"normalized":[{"db_name":"MESH","db_id":"D009410"}]},{"id":"5879","type":"Chemical","text":["iron"],"offsets":[[1140,1144]],"normalized":[{"db_name":"MESH","db_id":"D007501"}]},{"id":"5880","type":"Chemical","text":["iron"],"offsets":[[1217,1221]],"normalized":[{"db_name":"MESH","db_id":"D007501"}]}],"events":[],"coreferences":[],"relations":[{"id":"5881","type":"CID","arg1_id":"5862","arg2_id":"5863","normalized":[]},{"id":"5882","type":"CID","arg1_id":"5862","arg2_id":"5869","normalized":[]},{"id":"5883","type":"CID","arg1_id":"5862","arg2_id":"5878","normalized":[]},{"id":"5884","type":"CID","arg1_id":"5871","arg2_id":"5863","normalized":[]},{"id":"5885","type":"CID","arg1_id":"5871","arg2_id":"5869","normalized":[]},{"id":"5886","type":"CID","arg1_id":"5871","arg2_id":"5878","normalized":[]},{"id":"5887","type":"CID","arg1_id":"5872","arg2_id":"5863","normalized":[]},{"id":"5888","type":"CID","arg1_id":"5872","arg2_id":"5869","normalized":[]},{"id":"5889","type":"CID","arg1_id":"5872","arg2_id":"5878","normalized":[]},{"id":"5890","type":"CID","arg1_id":"5875","arg2_id":"5863","normalized":[]},{"id":"5891","type":"CID","arg1_id":"5875","arg2_id":"5869","normalized":[]},{"id":"5892","type":"CID","arg1_id":"5875","arg2_id":"5878","normalized":[]}]}
{"id":"5893","document_id":"16047871","passages":[{"id":"5894","type":"title","text":["Warfarin-induced leukocytoclastic vasculitis."],"offsets":[[0,45]]},{"id":"5895","type":"abstract","text":["Skin reactions associated with oral coumarin-derived anticoagulants are an uncommon occurrence. Leukocytoclastic vasculitis (LV) is primarily a cutaneous small vessel vasculitis, though systemic involvement may be encountered. We report 4 patients with late-onset LV probably due to warfarin. All 4 patients presented with skin eruptions that developed after receiving warfarin for several years. The results of skin lesion biopsies were available in 3 patients, confirming LV Cutaneous lesions resolved in all patients after warfarin was discontinued. In 2 of the 4 patients, rechallenge with warfarin led to recurrence of the lesions. LV may be a late-onset adverse reaction associated with warfarin therapy."],"offsets":[[46,756]]}],"entities":[{"id":"5896","type":"Chemical","text":["Warfarin"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"5897","type":"Disease","text":["leukocytoclastic vasculitis"],"offsets":[[17,44]],"normalized":[{"db_name":"MESH","db_id":"C535509"}]},{"id":"5898","type":"Chemical","text":["coumarin"],"offsets":[[82,90]],"normalized":[{"db_name":"MESH","db_id":"C030123"}]},{"id":"5899","type":"Disease","text":["Leukocytoclastic vasculitis"],"offsets":[[142,169]],"normalized":[{"db_name":"MESH","db_id":"C535509"}]},{"id":"5900","type":"Disease","text":["LV"],"offsets":[[171,173]],"normalized":[{"db_name":"MESH","db_id":"C535509"}]},{"id":"5901","type":"Disease","text":["cutaneous small vessel vasculitis"],"offsets":[[190,223]],"normalized":[{"db_name":"MESH","db_id":"C565222"}]},{"id":"5902","type":"Disease","text":["LV"],"offsets":[[310,312]],"normalized":[{"db_name":"MESH","db_id":"C535509"}]},{"id":"5903","type":"Chemical","text":["warfarin"],"offsets":[[329,337]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"5904","type":"Disease","text":["skin eruptions"],"offsets":[[369,383]],"normalized":[{"db_name":"MESH","db_id":"D012871"}]},{"id":"5905","type":"Chemical","text":["warfarin"],"offsets":[[415,423]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"5906","type":"Disease","text":["skin lesion"],"offsets":[[458,469]],"normalized":[{"db_name":"MESH","db_id":"D012871"}]},{"id":"5907","type":"Disease","text":["LV Cutaneous lesions"],"offsets":[[520,540]],"normalized":[{"db_name":"MESH","db_id":"D018366"}]},{"id":"5908","type":"Chemical","text":["warfarin"],"offsets":[[572,580]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"5909","type":"Chemical","text":["warfarin"],"offsets":[[640,648]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"5910","type":"Disease","text":["LV"],"offsets":[[683,685]],"normalized":[{"db_name":"MESH","db_id":"C535509"}]},{"id":"5911","type":"Chemical","text":["warfarin"],"offsets":[[739,747]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]}],"events":[],"coreferences":[],"relations":[{"id":"5912","type":"CID","arg1_id":"5896","arg2_id":"5907","normalized":[]},{"id":"5913","type":"CID","arg1_id":"5903","arg2_id":"5907","normalized":[]},{"id":"5914","type":"CID","arg1_id":"5905","arg2_id":"5907","normalized":[]},{"id":"5915","type":"CID","arg1_id":"5908","arg2_id":"5907","normalized":[]},{"id":"5916","type":"CID","arg1_id":"5909","arg2_id":"5907","normalized":[]},{"id":"5917","type":"CID","arg1_id":"5911","arg2_id":"5907","normalized":[]}]}
{"id":"5918","document_id":"15673851","passages":[{"id":"5919","type":"title","text":["The activation of spinal N-methyl-D-aspartate receptors may contribute to degeneration of spinal motor neurons induced by neuraxial morphine after a noninjurious interval of spinal cord ischemia."],"offsets":[[0,195]]},{"id":"5920","type":"abstract","text":["We investigated the relationship between the degeneration of spinal motor neurons and activation of N-methyl-d-aspartate (NMDA) receptors after neuraxial morphine following a noninjurious interval of aortic occlusion in rats. Spinal cord ischemia was induced by aortic occlusion for 6 min with a balloon catheter. In a microdialysis study, 10 muL of saline (group C; n = 8) or 30 mug of morphine (group M; n = 8) was injected intrathecally (IT) 0.5 h after reflow, and 30 mug of morphine (group SM; n = 8) or 10 muL of saline (group SC; n = 8) was injected IT 0.5 h after sham operation. Microdialysis samples were collected preischemia, before IT injection, and at 2, 4, 8, 24, and 48 h of reperfusion (after IT injection). Second, we investigated the effect of IT MK-801 (30 mug) on the histopathologic changes in the spinal cord after morphine-induced spastic paraparesis. After IT morphine, the cerebrospinal fluid (CSF) glutamate concentration was increased in group M relative to both baseline and group C (P < 0.05). This increase persisted for 8 hrs. IT MK-801 significantly reduced the number of dark-stained alpha-motoneurons after morphine-induced spastic paraparesis compared with the saline group. These data indicate that IT morphine induces spastic paraparesis with a concomitant increase in CSF glutamate, which is involved in NMDA receptor activation. We suggest that opioids may be neurotoxic in the setting of spinal cord ischemia via NMDA receptor activation."],"offsets":[[196,1675]]}],"entities":[{"id":"5921","type":"Chemical","text":["N-methyl-D-aspartate"],"offsets":[[25,45]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"5922","type":"Chemical","text":["morphine"],"offsets":[[132,140]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"5923","type":"Disease","text":["spinal cord ischemia"],"offsets":[[174,194]],"normalized":[{"db_name":"MESH","db_id":"D020760"}]},{"id":"5924","type":"Chemical","text":["N-methyl-d-aspartate"],"offsets":[[296,316]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"5925","type":"Chemical","text":["NMDA"],"offsets":[[318,322]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"5926","type":"Chemical","text":["morphine"],"offsets":[[350,358]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"5927","type":"Disease","text":["aortic occlusion"],"offsets":[[396,412]],"normalized":[{"db_name":"MESH","db_id":"D001157"}]},{"id":"5928","type":"Disease","text":["Spinal cord ischemia"],"offsets":[[422,442]],"normalized":[{"db_name":"MESH","db_id":"D020760"}]},{"id":"5929","type":"Disease","text":["aortic occlusion"],"offsets":[[458,474]],"normalized":[{"db_name":"MESH","db_id":"D001157"}]},{"id":"5930","type":"Chemical","text":["morphine"],"offsets":[[583,591]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"5931","type":"Chemical","text":["morphine"],"offsets":[[675,683]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"5932","type":"Chemical","text":["MK-801"],"offsets":[[962,968]],"normalized":[{"db_name":"MESH","db_id":"D016291"}]},{"id":"5933","type":"Chemical","text":["morphine"],"offsets":[[1034,1042]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"5934","type":"Disease","text":["spastic paraparesis"],"offsets":[[1051,1070]],"normalized":[{"db_name":"MESH","db_id":"D020336"}]},{"id":"5935","type":"Chemical","text":["morphine"],"offsets":[[1081,1089]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"5936","type":"Chemical","text":["glutamate"],"offsets":[[1121,1130]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"5937","type":"Chemical","text":["MK-801"],"offsets":[[1258,1264]],"normalized":[{"db_name":"MESH","db_id":"D016291"}]},{"id":"5938","type":"Chemical","text":["morphine"],"offsets":[[1338,1346]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"5939","type":"Disease","text":["spastic paraparesis"],"offsets":[[1355,1374]],"normalized":[{"db_name":"MESH","db_id":"D020336"}]},{"id":"5940","type":"Chemical","text":["morphine"],"offsets":[[1435,1443]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"5941","type":"Disease","text":["spastic paraparesis"],"offsets":[[1452,1471]],"normalized":[{"db_name":"MESH","db_id":"D020336"}]},{"id":"5942","type":"Chemical","text":["glutamate"],"offsets":[[1507,1516]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"5943","type":"Chemical","text":["NMDA"],"offsets":[[1539,1543]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"5944","type":"Disease","text":["neurotoxic"],"offsets":[[1596,1606]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"5945","type":"Disease","text":["spinal cord ischemia"],"offsets":[[1625,1645]],"normalized":[{"db_name":"MESH","db_id":"D020760"}]},{"id":"5946","type":"Chemical","text":["NMDA"],"offsets":[[1650,1654]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]}],"events":[],"coreferences":[],"relations":[{"id":"5947","type":"CID","arg1_id":"5922","arg2_id":"5934","normalized":[]},{"id":"5948","type":"CID","arg1_id":"5922","arg2_id":"5939","normalized":[]},{"id":"5949","type":"CID","arg1_id":"5922","arg2_id":"5941","normalized":[]},{"id":"5950","type":"CID","arg1_id":"5926","arg2_id":"5934","normalized":[]},{"id":"5951","type":"CID","arg1_id":"5926","arg2_id":"5939","normalized":[]},{"id":"5952","type":"CID","arg1_id":"5926","arg2_id":"5941","normalized":[]},{"id":"5953","type":"CID","arg1_id":"5930","arg2_id":"5934","normalized":[]},{"id":"5954","type":"CID","arg1_id":"5930","arg2_id":"5939","normalized":[]},{"id":"5955","type":"CID","arg1_id":"5930","arg2_id":"5941","normalized":[]},{"id":"5956","type":"CID","arg1_id":"5931","arg2_id":"5934","normalized":[]},{"id":"5957","type":"CID","arg1_id":"5931","arg2_id":"5939","normalized":[]},{"id":"5958","type":"CID","arg1_id":"5931","arg2_id":"5941","normalized":[]},{"id":"5959","type":"CID","arg1_id":"5933","arg2_id":"5934","normalized":[]},{"id":"5960","type":"CID","arg1_id":"5933","arg2_id":"5939","normalized":[]},{"id":"5961","type":"CID","arg1_id":"5933","arg2_id":"5941","normalized":[]},{"id":"5962","type":"CID","arg1_id":"5935","arg2_id":"5934","normalized":[]},{"id":"5963","type":"CID","arg1_id":"5935","arg2_id":"5939","normalized":[]},{"id":"5964","type":"CID","arg1_id":"5935","arg2_id":"5941","normalized":[]},{"id":"5965","type":"CID","arg1_id":"5938","arg2_id":"5934","normalized":[]},{"id":"5966","type":"CID","arg1_id":"5938","arg2_id":"5939","normalized":[]},{"id":"5967","type":"CID","arg1_id":"5938","arg2_id":"5941","normalized":[]},{"id":"5968","type":"CID","arg1_id":"5940","arg2_id":"5934","normalized":[]},{"id":"5969","type":"CID","arg1_id":"5940","arg2_id":"5939","normalized":[]},{"id":"5970","type":"CID","arg1_id":"5940","arg2_id":"5941","normalized":[]}]}
{"id":"5971","document_id":"12481039","passages":[{"id":"5972","type":"title","text":["Reduced sodium channel density, altered voltage dependence of inactivation, and increased susceptibility to seizures in mice lacking sodium channel beta 2-subunits."],"offsets":[[0,164]]},{"id":"5973","type":"abstract","text":["Sodium channel beta-subunits modulate channel gating, assembly, and cell surface expression in heterologous cell systems. We generated beta2(-\/-) mice to investigate the role of beta2 in control of sodium channel density, localization, and function in neurons in vivo. Measurements of [(3)H]saxitoxin (STX) binding showed a significant reduction in the level of plasma membrane sodium channels in beta2(-\/-) neurons. The loss of beta2 resulted in negative shifts in the voltage dependence of inactivation as well as significant decreases in sodium current density in acutely dissociated hippocampal neurons. The integral of the compound action potential in optic nerve was significantly reduced, and the threshold for action potential generation was increased, indicating a reduction in the level of functional plasma membrane sodium channels. In contrast, the conduction velocity, the number and size of axons in the optic nerve, and the specific localization of Na(v)1.6 channels in the nodes of Ranvier were unchanged. beta2(-\/-) mice displayed increased susceptibility to seizures, as indicated by reduced latency and threshold for pilocarpine-induced seizures, but seemed normal in other neurological tests. Our observations show that beta2-subunits play an important role in the regulation of sodium channel density and function in neurons in vivo and are required for normal action potential generation and control of excitability."],"offsets":[[165,1603]]}],"entities":[{"id":"5974","type":"Chemical","text":["sodium"],"offsets":[[8,14]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"5975","type":"Disease","text":["seizures"],"offsets":[[108,116]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"5976","type":"Chemical","text":["sodium"],"offsets":[[133,139]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"5977","type":"Chemical","text":["Sodium"],"offsets":[[165,171]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"5978","type":"Chemical","text":["sodium"],"offsets":[[363,369]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"5979","type":"Chemical","text":["saxitoxin"],"offsets":[[456,465]],"normalized":[{"db_name":"MESH","db_id":"D012530"}]},{"id":"5980","type":"Chemical","text":["STX"],"offsets":[[467,470]],"normalized":[{"db_name":"MESH","db_id":"D012530"}]},{"id":"5981","type":"Chemical","text":["sodium"],"offsets":[[543,549]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"5982","type":"Chemical","text":["sodium"],"offsets":[[706,712]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"5983","type":"Chemical","text":["sodium"],"offsets":[[992,998]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"5984","type":"Chemical","text":["Na"],"offsets":[[1129,1131]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"5985","type":"Disease","text":["seizures"],"offsets":[[1241,1249]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"5986","type":"Chemical","text":["pilocarpine"],"offsets":[[1301,1312]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"5987","type":"Disease","text":["seizures"],"offsets":[[1321,1329]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"5988","type":"Chemical","text":["sodium"],"offsets":[[1464,1470]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]}],"events":[],"coreferences":[],"relations":[{"id":"5989","type":"CID","arg1_id":"5986","arg2_id":"5975","normalized":[]},{"id":"5990","type":"CID","arg1_id":"5986","arg2_id":"5985","normalized":[]},{"id":"5991","type":"CID","arg1_id":"5986","arg2_id":"5987","normalized":[]}]}
{"id":"5992","document_id":"11185967","passages":[{"id":"5993","type":"title","text":["Screening for stimulant use in adult emergency department seizure patients."],"offsets":[[0,75]]},{"id":"5994","type":"abstract","text":["OBJECTIVE: The objective of this study was to determine the prevalence of positive plasma drug screening for cocaine or amphetamine in adult emergency department seizure patients. METHODS: This prospective study evaluated consecutive eligible seizure patients who had a plasma sample collected as part of their clinical evaluation. Plasma was tested for amphetamine and the cocaine metabolite benzoylecgonine using enzyme-mediated immunoassay methodology. Plasma samples with benzoylecgonine greater than 150 ng\/mL or an amphetamine greater than 500 ng\/mL were defined as positive. Patient demographics, history of underlying drug or alcohol-related seizure disorder, estimated time from seizure to sample collection, history or suspicion of cocaine or amphetamine abuse, results of clinical urine testing for drugs of abuse, and assay results were recorded without patient identifiers. RESULTS: Fourteen of 248 (5.6%, 95% CI 2.7%-8.5%) plasma samples were positive by immunoassay testing for benzoylecgonine and no samples (0%, 95% CI 0-1.2%) were positive for amphetamine. Positive test results were more common in patient visits where there was a history or suspicion of cocaine or amphetamine abuse (p < 0.0005). CONCLUSIONS: During this study period, routine plasma screening for cocaine and amphetamines in adult seizure patients had a low yield. As a result, routine plasma screening would yield few cases of stimulant drug in which there was neither a history nor suspicion of drug abuse in this population."],"offsets":[[76,1591]]}],"entities":[{"id":"5995","type":"Disease","text":["seizure"],"offsets":[[58,65]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"5996","type":"Chemical","text":["cocaine"],"offsets":[[185,192]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"5997","type":"Chemical","text":["amphetamine"],"offsets":[[196,207]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"5998","type":"Disease","text":["seizure"],"offsets":[[238,245]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"5999","type":"Disease","text":["seizure"],"offsets":[[319,326]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"6000","type":"Chemical","text":["amphetamine"],"offsets":[[430,441]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"6001","type":"Chemical","text":["cocaine"],"offsets":[[450,457]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6002","type":"Chemical","text":["benzoylecgonine"],"offsets":[[469,484]],"normalized":[{"db_name":"MESH","db_id":"C005618"}]},{"id":"6003","type":"Chemical","text":["benzoylecgonine"],"offsets":[[552,567]],"normalized":[{"db_name":"MESH","db_id":"C005618"}]},{"id":"6004","type":"Chemical","text":["amphetamine"],"offsets":[[597,608]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"6005","type":"Chemical","text":["alcohol"],"offsets":[[710,717]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"6006","type":"Disease","text":["seizure"],"offsets":[[726,733]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"6007","type":"Disease","text":["seizure"],"offsets":[[764,771]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"6008","type":"Disease","text":["cocaine or amphetamine abuse"],"offsets":[[818,846]],"normalized":[{"db_name":"MESH","db_id":"D019970"},{"db_name":"MESH","db_id":"D019969"}]},{"id":"6009","type":"Disease","text":["cocaine","abuse"],"offsets":[[818,825],[841,846]],"normalized":[{"db_name":"MESH","db_id":"D019970"}]},{"id":"6010","type":"Disease","text":["amphetamine abuse"],"offsets":[[829,846]],"normalized":[{"db_name":"MESH","db_id":"D019969"}]},{"id":"6011","type":"Chemical","text":["benzoylecgonine"],"offsets":[[1069,1084]],"normalized":[{"db_name":"MESH","db_id":"C005618"}]},{"id":"6012","type":"Chemical","text":["amphetamine"],"offsets":[[1138,1149]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"6013","type":"Disease","text":["cocaine or amphetamine abuse"],"offsets":[[1250,1278]],"normalized":[{"db_name":"MESH","db_id":"D019970"},{"db_name":"MESH","db_id":"D019969"}]},{"id":"6014","type":"Disease","text":["cocaine","abuse"],"offsets":[[1250,1257],[1273,1278]],"normalized":[{"db_name":"MESH","db_id":"D019970"}]},{"id":"6015","type":"Disease","text":["amphetamine abuse"],"offsets":[[1261,1278]],"normalized":[{"db_name":"MESH","db_id":"D019969"}]},{"id":"6016","type":"Chemical","text":["cocaine"],"offsets":[[1361,1368]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6017","type":"Chemical","text":["amphetamines"],"offsets":[[1373,1385]],"normalized":[{"db_name":"MESH","db_id":"D000662"}]},{"id":"6018","type":"Disease","text":["seizure"],"offsets":[[1395,1402]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"6019","type":"Disease","text":["drug abuse"],"offsets":[[1561,1571]],"normalized":[{"db_name":"MESH","db_id":"D019966"}]}],"events":[],"coreferences":[],"relations":[{"id":"6020","type":"CID","arg1_id":"6002","arg2_id":"5995","normalized":[]},{"id":"6021","type":"CID","arg1_id":"6002","arg2_id":"5998","normalized":[]},{"id":"6022","type":"CID","arg1_id":"6002","arg2_id":"5999","normalized":[]},{"id":"6023","type":"CID","arg1_id":"6002","arg2_id":"6006","normalized":[]},{"id":"6024","type":"CID","arg1_id":"6002","arg2_id":"6007","normalized":[]},{"id":"6025","type":"CID","arg1_id":"6002","arg2_id":"6018","normalized":[]},{"id":"6026","type":"CID","arg1_id":"6003","arg2_id":"5995","normalized":[]},{"id":"6027","type":"CID","arg1_id":"6003","arg2_id":"5998","normalized":[]},{"id":"6028","type":"CID","arg1_id":"6003","arg2_id":"5999","normalized":[]},{"id":"6029","type":"CID","arg1_id":"6003","arg2_id":"6006","normalized":[]},{"id":"6030","type":"CID","arg1_id":"6003","arg2_id":"6007","normalized":[]},{"id":"6031","type":"CID","arg1_id":"6003","arg2_id":"6018","normalized":[]},{"id":"6032","type":"CID","arg1_id":"6011","arg2_id":"5995","normalized":[]},{"id":"6033","type":"CID","arg1_id":"6011","arg2_id":"5998","normalized":[]},{"id":"6034","type":"CID","arg1_id":"6011","arg2_id":"5999","normalized":[]},{"id":"6035","type":"CID","arg1_id":"6011","arg2_id":"6006","normalized":[]},{"id":"6036","type":"CID","arg1_id":"6011","arg2_id":"6007","normalized":[]},{"id":"6037","type":"CID","arg1_id":"6011","arg2_id":"6018","normalized":[]}]}
{"id":"6038","document_id":"11099450","passages":[{"id":"6039","type":"title","text":["Evidence of functional somatotopy in GPi from results of pallidotomy."],"offsets":[[0,69]]},{"id":"6040","type":"abstract","text":["The objective of this study was to explore the functional anatomy of the globus pallidus internus (GPi) by studying the effects of unilateral pallidotomy on parkinsonian 'off' signs and levodopa-induced dyskinesias (LID). We found significant positive correlations between the preoperative levodopa responsiveness of motor signs and the levodopa responsiveness of scores in timed tests (Core Assessment Program for Intracerebral Transplantations) in the contralateral limbs and the improvement in these scores after surgery, whereas there was no correlation with the improvement in LID. We also found a highly significant correlation (P: < 0.0001, r = 0.8) between the volume of the ventral lesion in the GPi and the improvement in LID in the contralateral limbs, whereas there was no correlation between the ventral volume and the improvement in parkinsonian 'off' signs. The volumes of the total lesion cylinder and the dorsal lesion did not correlate with the outcome of either dyskinesias or parkinsonian 'off' signs. The differential predictive value of levodopa responsiveness for the outcome of parkinsonian 'off' signs and LID and the different correlations of ventral lesion volume with dyskinesias and parkinsonian 'off' signs indicate that different anatomical or pathophysiological substrates may be responsible for the generation of parkinsonian 'off' signs and dyskinesias. Whereas cells in a wider area of the GPi may be implicated in parkinsonism, the ventral GPi seems to be crucial for the manifestation of LID. We suggest that our observations are additional proof of the functional somatotopy of the systems within the GPi that mediate parkinsonism and dyskinesias, especially along the dorsoventral trajectory used in pallidotomy. The outcome of pallidotomy in which the lesion involves the ventral and dorsal GPi could be the net effect of alteration in the activity of pathways which mediate different symptoms, and hence could be variable."],"offsets":[[70,2033]]}],"entities":[{"id":"6041","type":"Disease","text":["parkinsonian"],"offsets":[[227,239]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"6042","type":"Chemical","text":["levodopa"],"offsets":[[256,264]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"6043","type":"Disease","text":["dyskinesias"],"offsets":[[273,284]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"6044","type":"Disease","text":["LID"],"offsets":[[286,289]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"6045","type":"Chemical","text":["levodopa"],"offsets":[[360,368]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"6046","type":"Chemical","text":["levodopa"],"offsets":[[407,415]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"6047","type":"Disease","text":["LID"],"offsets":[[652,655]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"6048","type":"Disease","text":["LID"],"offsets":[[802,805]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"6049","type":"Disease","text":["parkinsonian"],"offsets":[[917,929]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"6050","type":"Disease","text":["dyskinesias"],"offsets":[[1051,1062]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"6051","type":"Disease","text":["parkinsonian"],"offsets":[[1066,1078]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"6052","type":"Chemical","text":["levodopa"],"offsets":[[1129,1137]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"6053","type":"Disease","text":["parkinsonian"],"offsets":[[1172,1184]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"6054","type":"Disease","text":["LID"],"offsets":[[1201,1204]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"6055","type":"Disease","text":["dyskinesias"],"offsets":[[1266,1277]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"6056","type":"Disease","text":["parkinsonian"],"offsets":[[1282,1294]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"6057","type":"Disease","text":["parkinsonian"],"offsets":[[1416,1428]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"6058","type":"Disease","text":["dyskinesias"],"offsets":[[1445,1456]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"6059","type":"Disease","text":["parkinsonism"],"offsets":[[1520,1532]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"6060","type":"Disease","text":["LID"],"offsets":[[1595,1598]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"6061","type":"Disease","text":["parkinsonism"],"offsets":[[1726,1738]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"6062","type":"Disease","text":["dyskinesias"],"offsets":[[1743,1754]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]}],"events":[],"coreferences":[],"relations":[{"id":"6063","type":"CID","arg1_id":"6042","arg2_id":"6043","normalized":[]},{"id":"6064","type":"CID","arg1_id":"6042","arg2_id":"6044","normalized":[]},{"id":"6065","type":"CID","arg1_id":"6042","arg2_id":"6047","normalized":[]},{"id":"6066","type":"CID","arg1_id":"6042","arg2_id":"6048","normalized":[]},{"id":"6067","type":"CID","arg1_id":"6042","arg2_id":"6050","normalized":[]},{"id":"6068","type":"CID","arg1_id":"6042","arg2_id":"6054","normalized":[]},{"id":"6069","type":"CID","arg1_id":"6042","arg2_id":"6055","normalized":[]},{"id":"6070","type":"CID","arg1_id":"6042","arg2_id":"6058","normalized":[]},{"id":"6071","type":"CID","arg1_id":"6042","arg2_id":"6060","normalized":[]},{"id":"6072","type":"CID","arg1_id":"6042","arg2_id":"6062","normalized":[]},{"id":"6073","type":"CID","arg1_id":"6045","arg2_id":"6043","normalized":[]},{"id":"6074","type":"CID","arg1_id":"6045","arg2_id":"6044","normalized":[]},{"id":"6075","type":"CID","arg1_id":"6045","arg2_id":"6047","normalized":[]},{"id":"6076","type":"CID","arg1_id":"6045","arg2_id":"6048","normalized":[]},{"id":"6077","type":"CID","arg1_id":"6045","arg2_id":"6050","normalized":[]},{"id":"6078","type":"CID","arg1_id":"6045","arg2_id":"6054","normalized":[]},{"id":"6079","type":"CID","arg1_id":"6045","arg2_id":"6055","normalized":[]},{"id":"6080","type":"CID","arg1_id":"6045","arg2_id":"6058","normalized":[]},{"id":"6081","type":"CID","arg1_id":"6045","arg2_id":"6060","normalized":[]},{"id":"6082","type":"CID","arg1_id":"6045","arg2_id":"6062","normalized":[]},{"id":"6083","type":"CID","arg1_id":"6046","arg2_id":"6043","normalized":[]},{"id":"6084","type":"CID","arg1_id":"6046","arg2_id":"6044","normalized":[]},{"id":"6085","type":"CID","arg1_id":"6046","arg2_id":"6047","normalized":[]},{"id":"6086","type":"CID","arg1_id":"6046","arg2_id":"6048","normalized":[]},{"id":"6087","type":"CID","arg1_id":"6046","arg2_id":"6050","normalized":[]},{"id":"6088","type":"CID","arg1_id":"6046","arg2_id":"6054","normalized":[]},{"id":"6089","type":"CID","arg1_id":"6046","arg2_id":"6055","normalized":[]},{"id":"6090","type":"CID","arg1_id":"6046","arg2_id":"6058","normalized":[]},{"id":"6091","type":"CID","arg1_id":"6046","arg2_id":"6060","normalized":[]},{"id":"6092","type":"CID","arg1_id":"6046","arg2_id":"6062","normalized":[]},{"id":"6093","type":"CID","arg1_id":"6052","arg2_id":"6043","normalized":[]},{"id":"6094","type":"CID","arg1_id":"6052","arg2_id":"6044","normalized":[]},{"id":"6095","type":"CID","arg1_id":"6052","arg2_id":"6047","normalized":[]},{"id":"6096","type":"CID","arg1_id":"6052","arg2_id":"6048","normalized":[]},{"id":"6097","type":"CID","arg1_id":"6052","arg2_id":"6050","normalized":[]},{"id":"6098","type":"CID","arg1_id":"6052","arg2_id":"6054","normalized":[]},{"id":"6099","type":"CID","arg1_id":"6052","arg2_id":"6055","normalized":[]},{"id":"6100","type":"CID","arg1_id":"6052","arg2_id":"6058","normalized":[]},{"id":"6101","type":"CID","arg1_id":"6052","arg2_id":"6060","normalized":[]},{"id":"6102","type":"CID","arg1_id":"6052","arg2_id":"6062","normalized":[]}]}
{"id":"6103","document_id":"11027904","passages":[{"id":"6104","type":"title","text":["Pain responses in methadone-maintained opioid abusers."],"offsets":[[0,54]]},{"id":"6105","type":"abstract","text":["Providing pain management for known opioid abusers is a challenging clinical task, in part because little is known about their pain experience and analgesic requirements. This study was designed to describe pain tolerance and analgesic response in a sample of opioid addicts stabilized in methadone-maintenance (MM) treatment (n = 60) in comparison to matched nondependent control subjects (n = 60). By using a placebo-controlled, two-way factorial design, tolerance to cold-pressor (CP) pain was examined, both before and after oral administration of therapeutic doses of common opioid (hydromorphone 2 mg) and nonsteroidal anti-inflammatory (ketorolac 10 mg) analgesic agents. Results showed that MM individuals were significantly less tolerant of CP pain than control subjects, replicating previous work. Analgesic effects were significant neither for medication nor group. These data indicate that MM opioid abusers represent a pain-intolerant subset of clinical patients. Their complaints of pain should be evaluated seriously and managed aggressively."],"offsets":[[55,1112]]}],"entities":[{"id":"6106","type":"Disease","text":["Pain"],"offsets":[[0,4]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"6107","type":"Chemical","text":["methadone"],"offsets":[[18,27]],"normalized":[{"db_name":"MESH","db_id":"D008691"}]},{"id":"6108","type":"Disease","text":["pain"],"offsets":[[65,69]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"6109","type":"Disease","text":["pain"],"offsets":[[182,186]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"6110","type":"Disease","text":["pain"],"offsets":[[262,266]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"6111","type":"Disease","text":["opioid addicts"],"offsets":[[315,329]],"normalized":[{"db_name":"MESH","db_id":"D009293"}]},{"id":"6112","type":"Chemical","text":["methadone"],"offsets":[[344,353]],"normalized":[{"db_name":"MESH","db_id":"D008691"}]},{"id":"6113","type":"Disease","text":["pain"],"offsets":[[543,547]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"6114","type":"Chemical","text":["hydromorphone"],"offsets":[[643,656]],"normalized":[{"db_name":"MESH","db_id":"D004091"}]},{"id":"6115","type":"Chemical","text":["ketorolac"],"offsets":[[699,708]],"normalized":[{"db_name":"MESH","db_id":"D020910"}]},{"id":"6116","type":"Disease","text":["pain"],"offsets":[[808,812]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"6117","type":"Disease","text":["pain-intolerant"],"offsets":[[987,1002]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"6118","type":"Disease","text":["pain"],"offsets":[[1052,1056]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]}],"events":[],"coreferences":[],"relations":[{"id":"6119","type":"CID","arg1_id":"6107","arg2_id":"6117","normalized":[]},{"id":"6120","type":"CID","arg1_id":"6112","arg2_id":"6117","normalized":[]}]}
{"id":"6121","document_id":"10193809","passages":[{"id":"6122","type":"title","text":["Urine N-acetyl-beta-D-glucosaminidase--a marker of tubular damage?"],"offsets":[[0,66]]},{"id":"6123","type":"abstract","text":["BACKGROUND: Although an indicator of renal tubular dysfunction, an increased urinary N-acetyl-beta-D-glucosaminidase (NAG) activity might reflect increased lysosomal activity in renal tubular cells. METHODS: Puromycin aminonucleoside (PAN) was administered to Sprague Dawley rats to induce proteinuria. Total protein, albumin, NAG activity and protein electrophoretic pattern were assessed in daily urine samples for 33 days. The morphological appearance of the kidneys was examined on days three, four, six, eight and thirty three and the NAG isoenzyme patterns on days zero, four, eight and thirty three. RESULTS: Following intravenous PAN urine volume and urine NAG activity increased significantly by day two, but returned to normal by day four. After day four all treated animals exhibited a marked rise in urine albumin, total protein excretion and NAG activity. Electrophoresis showed a generalised increase in middle and high molecular weight urine proteins from day four onwards. Protein droplets first appeared prominent in tubular cells on day four. Peak urine NAG activity and a change in NAG isoenzyme pattern coincided with both the peak proteinuria and the reduction in intracellular protein and NAG droplets (day six onwards). CONCLUSIONS: This animal model demonstrates that an increase in lysosomal turnover and hence urine NAG activity, occurs when increased protein is presented to the tubular cells. Urine NAG activity is thus a measure of altered function in the renal tubules and not simply an indicator of damage."],"offsets":[[67,1604]]}],"entities":[{"id":"6124","type":"Disease","text":["renal tubular dysfunction"],"offsets":[[104,129]],"normalized":[{"db_name":"MESH","db_id":"D005198"}]},{"id":"6125","type":"Chemical","text":["Puromycin aminonucleoside"],"offsets":[[275,300]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"6126","type":"Chemical","text":["PAN"],"offsets":[[302,305]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"6127","type":"Disease","text":["proteinuria"],"offsets":[[357,368]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"6128","type":"Chemical","text":["PAN"],"offsets":[[705,708]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"6129","type":"Disease","text":["proteinuria"],"offsets":[[1219,1230]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]}],"events":[],"coreferences":[],"relations":[{"id":"6130","type":"CID","arg1_id":"6125","arg2_id":"6127","normalized":[]},{"id":"6131","type":"CID","arg1_id":"6125","arg2_id":"6129","normalized":[]},{"id":"6132","type":"CID","arg1_id":"6126","arg2_id":"6127","normalized":[]},{"id":"6133","type":"CID","arg1_id":"6126","arg2_id":"6129","normalized":[]},{"id":"6134","type":"CID","arg1_id":"6128","arg2_id":"6127","normalized":[]},{"id":"6135","type":"CID","arg1_id":"6128","arg2_id":"6129","normalized":[]}]}
{"id":"6136","document_id":"9214597","passages":[{"id":"6137","type":"title","text":["Over expression of vascular endothelial growth factor and its receptor during the development of estrogen-induced rat pituitary tumors may mediate estrogen-initiated tumor angiogenesis."],"offsets":[[0,185]]},{"id":"6138","type":"abstract","text":["Estrogens, which have been associated with several types of human and animal cancers, can induce tumor angiogenesis in the pituitary of Fischer 344 rats. The mechanistic details of tumor angiogenesis induction, during estrogen carcinogenesis, are still unknown. To elucidate the role of estrogen in the regulation of tumor angiogenesis in the pituitary of female rats, the density of blood vessels was analysed using factor VIII related antigen (FVIIIRAg) immunohistochemistry and the expression of vascular endothelial growth factor\/vascular permeability factor (VEGF\/VPF) was examined by Western blot and immunohistochemical analysis. The expression of VEGF receptor (VEGFR-2\/Flk-1\/KDR) was also examined by immunohistochemistry. The results demonstrated that 17beta-estradiol (E2) induces neovascularization, as well as the growth and enlargement of blood vessels after 7 days of exposure. The high tumor angiogenic potential was associated with an elevated VEGF\/VPF protein expression in the E2 exposed pituitary of ovariectomized (OVEX) rats. VEGF\/VPF and FVIIIRAg immunohistochemistry and endothelial specific lectin (UEA1) binding studies, indicate that the elevation of VEGF protein expression initially occurred in both blood vessels and non-endothelial cells. After 15 days of E2 exposure, VEGF\/VPF protein expression, in the non-endothelial cell population, sharply declined and was restricted to the blood vessels. The function of non-endothelial-derived VEGF is not clear. Furthermore, immunohistochemical studies demonstrated that VEGFR-2 (flk-1\/KDR), expression was elevated significantly in the endothelial cells of microblood vessels after 7 days of E2 exposure. These findings suggest that over expression of VEGF and its receptor (VEGFR-2) may play an important role in the initial step of the regulation of estrogen induced tumor angiogenesis in the rat pituitary."],"offsets":[[186,2070]]}],"entities":[{"id":"6139","type":"Chemical","text":["estrogen"],"offsets":[[97,105]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"6140","type":"Disease","text":["pituitary tumors"],"offsets":[[118,134]],"normalized":[{"db_name":"MESH","db_id":"D010911"}]},{"id":"6141","type":"Chemical","text":["estrogen"],"offsets":[[147,155]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"6142","type":"Disease","text":["tumor"],"offsets":[[166,171]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"6143","type":"Chemical","text":["Estrogens"],"offsets":[[186,195]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"6144","type":"Disease","text":["cancers"],"offsets":[[263,270]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"6145","type":"Disease","text":["tumor"],"offsets":[[283,288]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"6146","type":"Disease","text":["tumor"],"offsets":[[367,372]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"6147","type":"Chemical","text":["estrogen"],"offsets":[[404,412]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"6148","type":"Disease","text":["carcinogenesis"],"offsets":[[413,427]],"normalized":[{"db_name":"MESH","db_id":"D063646"}]},{"id":"6149","type":"Chemical","text":["estrogen"],"offsets":[[473,481]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"6150","type":"Disease","text":["tumor"],"offsets":[[503,508]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"6151","type":"Chemical","text":["17beta-estradiol"],"offsets":[[948,964]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"6152","type":"Chemical","text":["E2"],"offsets":[[966,968]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"6153","type":"Disease","text":["tumor"],"offsets":[[1088,1093]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"6154","type":"Chemical","text":["E2"],"offsets":[[1182,1184]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"6155","type":"Chemical","text":["E2"],"offsets":[[1473,1475]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"6156","type":"Chemical","text":["E2"],"offsets":[[1853,1855]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"6157","type":"Chemical","text":["estrogen"],"offsets":[[2013,2021]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"6158","type":"Disease","text":["tumor"],"offsets":[[2030,2035]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]}],"events":[],"coreferences":[],"relations":[{"id":"6159","type":"CID","arg1_id":"6151","arg2_id":"6140","normalized":[]},{"id":"6160","type":"CID","arg1_id":"6152","arg2_id":"6140","normalized":[]},{"id":"6161","type":"CID","arg1_id":"6154","arg2_id":"6140","normalized":[]},{"id":"6162","type":"CID","arg1_id":"6155","arg2_id":"6140","normalized":[]},{"id":"6163","type":"CID","arg1_id":"6156","arg2_id":"6140","normalized":[]}]}
{"id":"6164","document_id":"7604176","passages":[{"id":"6165","type":"title","text":["Pravastatin-associated myopathy. Report of a case."],"offsets":[[0,50]]},{"id":"6166","type":"abstract","text":["A case of acute inflammatory myopathy associated with the use of pravastatin, a new hydrophilic 3-hydroxy-3 methylglutaril coenzyme A reductase inhibitor, is reported. The patient, a 69-year-old man was affected by non-insulin-dependent diabetes mellitus and hypertension. He assumed pravastatin (20 mg\/day) because of hypercholesterolemia. He was admitted with acute myopathy of the lower limbs which resolved in a few days after pravastatin discontinuation. A previously unknown hypothyroidism, probably due to chronic autoimmune thyroiditis, was evidenced. Muscle biopsy (left gastrocnemius) revealed a perimysial and endomysial inflammatory infiltrate with a prevalence of CD4+ lymphocytes. While lovastatin and simvastatin have been associated with toxic myopathy, pravastatin-associated myopathy could represent a distinct, inflammatory entity."],"offsets":[[51,901]]}],"entities":[{"id":"6167","type":"Chemical","text":["Pravastatin"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D017035"}]},{"id":"6168","type":"Disease","text":["myopathy"],"offsets":[[23,31]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"6169","type":"Disease","text":["inflammatory myopathy"],"offsets":[[67,88]],"normalized":[{"db_name":"MESH","db_id":"D009220"}]},{"id":"6170","type":"Chemical","text":["pravastatin"],"offsets":[[116,127]],"normalized":[{"db_name":"MESH","db_id":"D017035"}]},{"id":"6171","type":"Disease","text":["non-insulin-dependent diabetes mellitus"],"offsets":[[266,305]],"normalized":[{"db_name":"MESH","db_id":"D003924"}]},{"id":"6172","type":"Disease","text":["hypertension"],"offsets":[[310,322]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"6173","type":"Chemical","text":["pravastatin"],"offsets":[[335,346]],"normalized":[{"db_name":"MESH","db_id":"D017035"}]},{"id":"6174","type":"Disease","text":["hypercholesterolemia"],"offsets":[[370,390]],"normalized":[{"db_name":"MESH","db_id":"D006937"}]},{"id":"6175","type":"Disease","text":["myopathy"],"offsets":[[419,427]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"6176","type":"Chemical","text":["pravastatin"],"offsets":[[482,493]],"normalized":[{"db_name":"MESH","db_id":"D017035"}]},{"id":"6177","type":"Disease","text":["hypothyroidism"],"offsets":[[532,546]],"normalized":[{"db_name":"MESH","db_id":"D007037"}]},{"id":"6178","type":"Disease","text":["autoimmune thyroiditis"],"offsets":[[572,594]],"normalized":[{"db_name":"MESH","db_id":"D013967"}]},{"id":"6179","type":"Chemical","text":["lovastatin"],"offsets":[[752,762]],"normalized":[{"db_name":"MESH","db_id":"D008148"}]},{"id":"6180","type":"Chemical","text":["simvastatin"],"offsets":[[767,778]],"normalized":[{"db_name":"MESH","db_id":"D019821"}]},{"id":"6181","type":"Disease","text":["myopathy"],"offsets":[[811,819]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"6182","type":"Chemical","text":["pravastatin"],"offsets":[[821,832]],"normalized":[{"db_name":"MESH","db_id":"D017035"}]},{"id":"6183","type":"Disease","text":["myopathy"],"offsets":[[844,852]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]}],"events":[],"coreferences":[],"relations":[{"id":"6184","type":"CID","arg1_id":"6167","arg2_id":"6169","normalized":[]},{"id":"6185","type":"CID","arg1_id":"6170","arg2_id":"6169","normalized":[]},{"id":"6186","type":"CID","arg1_id":"6173","arg2_id":"6169","normalized":[]},{"id":"6187","type":"CID","arg1_id":"6176","arg2_id":"6169","normalized":[]},{"id":"6188","type":"CID","arg1_id":"6182","arg2_id":"6169","normalized":[]}]}
{"id":"6189","document_id":"7282516","passages":[{"id":"6190","type":"title","text":["Dose-effect and structure-function relationships in doxorubicin cardiomyopathy."],"offsets":[[0,79]]},{"id":"6191","type":"abstract","text":["The cardiomyopathy (CM) produced by the anticancer drug doxorubicin (DXR) (Adriamycin) provides a unique opportunity to analyze dose-effect and structure-function relationships during development of myocardial disease. We measured the degree of morphologic damage by ultrastructural examination of endomyocardial biopsy and the degree of performance abnormally by right heart catheterization in patients receiving DXR. Morphologic damage was variable but was proportional to the total cumulative DXR dose between 100 and 600 mg\/m2. Performance abnormalities correlated weakly with dose, exhibited a curvilinear relationship, and had a \"threshold\" for expression. Catheterization abnormalities correlated well with morphologic damage (r = 0.57 to 0.78) in a subgroup of patients in whom exercise hemodynamics were measured, and this relationship also exhibited a curvilinear, threshold configuration. In DXR-CM myocardial damage is proportional to the degree of cytotoxic insult (DXR dose) while myocardial function is preserved until a critical dose or degree of damage is reached, after which myocardial performance deteriorates rapidly."],"offsets":[[80,1218]]}],"entities":[{"id":"6192","type":"Chemical","text":["doxorubicin"],"offsets":[[52,63]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"6193","type":"Disease","text":["cardiomyopathy"],"offsets":[[64,78]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"6194","type":"Disease","text":["cardiomyopathy"],"offsets":[[84,98]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"6195","type":"Disease","text":["CM"],"offsets":[[100,102]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"6196","type":"Chemical","text":["doxorubicin"],"offsets":[[136,147]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"6197","type":"Chemical","text":["DXR"],"offsets":[[149,152]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"6198","type":"Chemical","text":["Adriamycin"],"offsets":[[155,165]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"6199","type":"Disease","text":["myocardial disease"],"offsets":[[279,297]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"6200","type":"Chemical","text":["DXR"],"offsets":[[494,497]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"6201","type":"Chemical","text":["DXR"],"offsets":[[576,579]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"6202","type":"Chemical","text":["DXR"],"offsets":[[983,986]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"6203","type":"Disease","text":["CM"],"offsets":[[987,989]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"6204","type":"Disease","text":["myocardial 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{"id":"6254","document_id":"7072798","passages":[{"id":"6255","type":"title","text":["Fatal aplastic anemia following topical administration of ophthalmic chloramphenicol."],"offsets":[[0,85]]},{"id":"6256","type":"abstract","text":["A 73-year-old woman died of aplastic anemia less than two months after undergoing cataract extraction and beginning topical therapy with chloramphenicol. The first signs of pancytopenia began within one month of the surgery. The pattern of the aplastic anemia was associated with an idiosyncratic response to chloramphenicol. This was the second report of fatal aplastic anemia after topical treatment with chloramphenicol for ocular conditions, although two cases of reversible bone marrow hypoplasia have also been reported. Any other suspected cases of ocular toxicity associated with topically applied chloramphenicol should be reported to the National Registry of Drug-Induced Ocular Side Effects, Oregon Health Sciences University, Portland, OR 97201."],"offsets":[[86,843]]}],"entities":[{"id":"6257","type":"Disease","text":["aplastic anemia"],"offsets":[[6,21]],"normalized":[{"db_name":"MESH","db_id":"D000741"}]},{"id":"6258","type":"Chemical","text":["chloramphenicol"],"offsets":[[69,84]],"normalized":[{"db_name":"MESH","db_id":"D002701"}]},{"id":"6259","type":"Disease","text":["aplastic anemia"],"offsets":[[114,129]],"normalized":[{"db_name":"MESH","db_id":"D000741"}]},{"id":"6260","type":"Disease","text":["cataract"],"offsets":[[168,176]],"normalized":[{"db_name":"MESH","db_id":"D002386"}]},{"id":"6261","type":"Chemical","text":["chloramphenicol"],"offsets":[[223,238]],"normalized":[{"db_name":"MESH","db_id":"D002701"}]},{"id":"6262","type":"Disease","text":["pancytopenia"],"offsets":[[259,271]],"normalized":[{"db_name":"MESH","db_id":"D010198"}]},{"id":"6263","type":"Disease","text":["aplastic anemia"],"offsets":[[330,345]],"normalized":[{"db_name":"MESH","db_id":"D000741"}]},{"id":"6264","type":"Chemical","text":["chloramphenicol"],"offsets":[[395,410]],"normalized":[{"db_name":"MESH","db_id":"D002701"}]},{"id":"6265","type":"Disease","text":["aplastic anemia"],"offsets":[[448,463]],"normalized":[{"db_name":"MESH","db_id":"D000741"}]},{"id":"6266","type":"Chemical","text":["chloramphenicol"],"offsets":[[493,508]],"normalized":[{"db_name":"MESH","db_id":"D002701"}]},{"id":"6267","type":"Disease","text":["bone marrow hypoplasia"],"offsets":[[565,587]],"normalized":[{"db_name":"MESH","db_id":"D001855"}]},{"id":"6268","type":"Disease","text":["ocular toxicity"],"offsets":[[642,657]],"normalized":[{"db_name":"MESH","db_id":"D005128"}]},{"id":"6269","type":"Chemical","text":["chloramphenicol"],"offsets":[[692,707]],"normalized":[{"db_name":"MESH","db_id":"D002701"}]}],"events":[],"coreferences":[],"relations":[{"id":"6270","type":"CID","arg1_id":"6258","arg2_id":"6257","normalized":[]},{"id":"6271","type":"CID","arg1_id":"6258","arg2_id":"6259","normalized":[]},{"id":"6272","type":"CID","arg1_id":"6258","arg2_id":"6263","normalized":[]},{"id":"6273","type":"CID","arg1_id":"6258","arg2_id":"6265","normalized":[]},{"id":"6274","type":"CID","arg1_id":"6261","arg2_id":"6257","normalized":[]},{"id":"6275","type":"CID","arg1_id":"6261","arg2_id":"6259","normalized":[]},{"id":"6276","type":"CID","arg1_id":"6261","arg2_id":"6263","normalized":[]},{"id":"6277","type":"CID","arg1_id":"6261","arg2_id":"6265","normalized":[]},{"id":"6278","type":"CID","arg1_id":"6264","arg2_id":"6257","normalized":[]},{"id":"6279","type":"CID","arg1_id":"6264","arg2_id":"6259","normalized":[]},{"id":"6280","type":"CID","arg1_id":"6264","arg2_id":"6263","normalized":[]},{"id":"6281","type":"CID","arg1_id":"6264","arg2_id":"6265","normalized":[]},{"id":"6282","type":"CID","arg1_id":"6266","arg2_id":"6257","normalized":[]},{"id":"6283","type":"CID","arg1_id":"6266","arg2_id":"6259","normalized":[]},{"id":"6284","type":"CID","arg1_id":"6266","arg2_id":"6263","normalized":[]},{"id":"6285","type":"CID","arg1_id":"6266","arg2_id":"6265","normalized":[]},{"id":"6286","type":"CID","arg1_id":"6269","arg2_id":"6257","normalized":[]},{"id":"6287","type":"CID","arg1_id":"6269","arg2_id":"6259","normalized":[]},{"id":"6288","type":"CID","arg1_id":"6269","arg2_id":"6263","normalized":[]},{"id":"6289","type":"CID","arg1_id":"6269","arg2_id":"6265","normalized":[]}]}
{"id":"6290","document_id":"3769769","passages":[{"id":"6291","type":"title","text":["Bradycardia due to trihexyphenidyl hydrochloride."],"offsets":[[0,49]]},{"id":"6292","type":"abstract","text":["A chronic schizophrenic patient was treated with an anticholinergic drug, trihexyphenidyl hydrochloride. The patient developed, paradoxically, sinus bradycardia. The reaction was specific to trihexyphenidyl and not to other anticholinergic drugs. This antidyskinetic drug is widely used in clinical psychiatric practice and physicians should be aware of this side effect."],"offsets":[[50,421]]}],"entities":[{"id":"6293","type":"Disease","text":["Bradycardia"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"6294","type":"Chemical","text":["trihexyphenidyl hydrochloride"],"offsets":[[19,48]],"normalized":[{"db_name":"MESH","db_id":"D014282"}]},{"id":"6295","type":"Disease","text":["schizophrenic"],"offsets":[[60,73]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"6296","type":"Chemical","text":["trihexyphenidyl hydrochloride"],"offsets":[[124,153]],"normalized":[{"db_name":"MESH","db_id":"D014282"}]},{"id":"6297","type":"Disease","text":["bradycardia"],"offsets":[[199,210]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"6298","type":"Chemical","text":["trihexyphenidyl"],"offsets":[[241,256]],"normalized":[{"db_name":"MESH","db_id":"D014282"}]},{"id":"6299","type":"Disease","text":["psychiatric"],"offsets":[[349,360]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]}],"events":[],"coreferences":[],"relations":[{"id":"6300","type":"CID","arg1_id":"6294","arg2_id":"6293","normalized":[]},{"id":"6301","type":"CID","arg1_id":"6294","arg2_id":"6297","normalized":[]},{"id":"6302","type":"CID","arg1_id":"6296","arg2_id":"6293","normalized":[]},{"id":"6303","type":"CID","arg1_id":"6296","arg2_id":"6297","normalized":[]},{"id":"6304","type":"CID","arg1_id":"6298","arg2_id":"6293","normalized":[]},{"id":"6305","type":"CID","arg1_id":"6298","arg2_id":"6297","normalized":[]}]}
{"id":"6306","document_id":"3708922","passages":[{"id":"6307","type":"title","text":["Experimental cyclosporine nephrotoxicity: risk of concomitant chemotherapy."],"offsets":[[0,75]]},{"id":"6308","type":"abstract","text":["The role of cyclosporine (CSA) alone or in combination with various chemotherapeutics in the development of renal toxicity was evaluated in rats. Administration of 20 mg\/kg\/day CSA for 4 weeks caused renal functional and structural changes similar to those reported in man. The combined administration of CSA and various chemotherapeutic drugs with a nephrotoxic potential, such as gentamicin (at therapeutic doses), amphothericin B and ketoconazole, which are frequently used in immunosuppressed patients, did not aggravate the CSA induced toxicity in the rat model. Gentamicin at toxic doses, however, increased CSA nephrotoxicity. Thus, the nephrotoxicity induced by CSA has a different pathogenetic mechanism."],"offsets":[[76,789]]}],"entities":[{"id":"6309","type":"Chemical","text":["cyclosporine"],"offsets":[[13,25]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"6310","type":"Disease","text":["nephrotoxicity"],"offsets":[[26,40]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"6311","type":"Chemical","text":["cyclosporine"],"offsets":[[88,100]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"6312","type":"Chemical","text":["CSA"],"offsets":[[102,105]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"6313","type":"Disease","text":["renal 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B"],"offsets":[[493,508]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"6319","type":"Chemical","text":["ketoconazole"],"offsets":[[513,525]],"normalized":[{"db_name":"MESH","db_id":"D007654"}]},{"id":"6320","type":"Chemical","text":["CSA"],"offsets":[[605,608]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"6321","type":"Disease","text":["toxicity"],"offsets":[[617,625]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"6322","type":"Chemical","text":["Gentamicin"],"offsets":[[644,654]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"6323","type":"Chemical","text":["CSA"],"offsets":[[690,693]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"6324","type":"Disease","text":["nephrotoxicity"],"offsets":[[694,708]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"6325","type":"Disease","text":["nephrotoxicity"],"offsets":[[720,734]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"6326","type":"Chemical","text":["CSA"],"offsets":[[746,749]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]}],"events":[],"coreferences":[],"relations":[{"id":"6327","type":"CID","arg1_id":"6309","arg2_id":"6310","normalized":[]},{"id":"6328","type":"CID","arg1_id":"6309","arg2_id":"6313","normalized":[]},{"id":"6329","type":"CID","arg1_id":"6309","arg2_id":"6316","normalized":[]},{"id":"6330","type":"CID","arg1_id":"6309","arg2_id":"6324","normalized":[]},{"id":"6331","type":"CID","arg1_id":"6309","arg2_id":"6325","normalized":[]},{"id":"6332","type":"CID","arg1_id":"6311","arg2_id":"6310","normalized":[]},{"id":"6333","type":"CID","arg1_id":"6311","arg2_id":"6313","normalized":[]},{"id":"6334","type":"CID","arg1_id":"6311","arg2_id":"6316","normalized":[]},{"id":"6335","type":"CID","arg1_id":"6311","arg2_id":"6324","normalized":[]},{"id":"6336","type":"CID","arg1_id":"6311","arg2_id":"6325","normalized":[]},{"id":"6337","type":"CID","arg1_id":"6312","arg2_id":"6310","normalized":[]},{"id":"6338","type":"CID","arg1_id":"6312","arg2_id":"6313","normalized":[]},{"id":"6339","type":"CID","arg1_id":"6312","arg2_id":"6316","normalized":[]},{"id":"6340","type":"CID","arg1_id":"6312","arg2_id":"6324","normalized":[]},{"id":"6341","type":"CID","arg1_id":"6312","arg2_id":"6325","normalized":[]},{"id":"6342","type":"CID","arg1_id":"6314","arg2_id":"6310","normalized":[]},{"id":"6343","type":"CID","arg1_id":"6314","arg2_id":"6313","normalized":[]},{"id":"6344","type":"CID","arg1_id":"6314","arg2_id":"6316","normalized":[]},{"id":"6345","type":"CID","arg1_id":"6314","arg2_id":"6324","normalized":[]},{"id":"6346","type":"CID","arg1_id":"6314","arg2_id":"6325","normalized":[]},{"id":"6347","type":"CID","arg1_id":"6315","arg2_id":"6310","normalized":[]},{"id":"6348","type":"CID","arg1_id":"6315","arg2_id":"6313","normalized":[]},{"id":"6349","type":"CID","arg1_id":"6315","arg2_id":"6316","normalized":[]},{"id":"6350","type":"CID","arg1_id":"6315","arg2_id":"6324","normalized":[]},{"id":"6351","type":"CID","arg1_id":"6315","arg2_id":"6325","normalized":[]},{"id":"6352","type":"CID","arg1_id":"6320","arg2_id":"6310","normalized":[]},{"id":"6353","type":"CID","arg1_id":"6320","arg2_id":"6313","normalized":[]},{"id":"6354","type":"CID","arg1_id":"6320","arg2_id":"6316","normalized":[]},{"id":"6355","type":"CID","arg1_id":"6320","arg2_id":"6324","normalized":[]},{"id":"6356","type":"CID","arg1_id":"6320","arg2_id":"6325","normalized":[]},{"id":"6357","type":"CID","arg1_id":"6323","arg2_id":"6310","normalized":[]},{"id":"6358","type":"CID","arg1_id":"6323","arg2_id":"6313","normalized":[]},{"id":"6359","type":"CID","arg1_id":"6323","arg2_id":"6316","normalized":[]},{"id":"6360","type":"CID","arg1_id":"6323","arg2_id":"6324","normalized":[]},{"id":"6361","type":"CID","arg1_id":"6323","arg2_id":"6325","normalized":[]},{"id":"6362","type":"CID","arg1_id":"6326","arg2_id":"6310","normalized":[]},{"id":"6363","type":"CID","arg1_id":"6326","arg2_id":"6313","normalized":[]},{"id":"6364","type":"CID","arg1_id":"6326","arg2_id":"6316","normalized":[]},{"id":"6365","type":"CID","arg1_id":"6326","arg2_id":"6324","normalized":[]},{"id":"6366","type":"CID","arg1_id":"6326","arg2_id":"6325","normalized":[]}]}
{"id":"6367","document_id":"3220106","passages":[{"id":"6368","type":"title","text":["Receptor mechanisms of nicotine-induced locomotor hyperactivity in chronic nicotine-treated rats."],"offsets":[[0,97]]},{"id":"6369","type":"abstract","text":["Rats were pretreated with saline or nicotine (1.5 mg\/kg per day) by subcutaneously implanting each animal with an Alzet osmotic mini-pump which continuously released saline or nicotine for 1, 5 and 14 days. At the end of each pretreatment period, animals were used for (i) determining their locomotor response to acutely injected nicotine (0.2 mg\/kg, s.c.) and (ii) measuring the density of L-[3H]nicotine and [3H]spiperone binding sites in the striatum. We observed no changes in nicotine-induced locomotor response, striatal L-[3H]nicotine and [3H]spiperone binding in the animals pretreated with nicotine for 1 day. In rats which were pretreated with nicotine for 5 days, there was a significant increase in the nicotine-stimulated locomotor response which was associated with an increase in the number of L-[3H]nicotine binding sites and also with an elevated dopamine (DA) level in the striatum. The number of striatal [3H]spiperone binding sites was not affected. In animals pretreated with nicotine for 14 days, the nicotine-induced locomotor response remained to be potentiated. However, this response was correlated with an elevated number of striatal [3H]spiperone binding sites, whereas the number of striatal L-[3H]nicotine binding sites and the striatal DA level were normal. These results suggest that chronic nicotine-treated rats develop locomotor hyperactivity in response to nicotine initially due to increases of both the density of nicotinic receptors and DA concentration, followed by inducing DA receptor supersensitivity in the striatum."],"offsets":[[98,1658]]}],"entities":[{"id":"6370","type":"Chemical","text":["nicotine"],"offsets":[[23,31]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"6371","type":"Disease","text":["locomotor 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hyperactivity"],"offsets":[[1452,1475]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"6395","type":"Chemical","text":["nicotine"],"offsets":[[1491,1499]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"6396","type":"Chemical","text":["DA"],"offsets":[[1574,1576]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"6397","type":"Chemical","text":["DA"],"offsets":[[1613,1615]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]}],"events":[],"coreferences":[],"relations":[{"id":"6398","type":"CID","arg1_id":"6370","arg2_id":"6371","normalized":[]},{"id":"6399","type":"CID","arg1_id":"6370","arg2_id":"6394","normalized":[]},{"id":"6400","type":"CID","arg1_id":"6372","arg2_id":"6371","normalized":[]},{"id":"6401","type":"CID","arg1_id":"6372","arg2_id":"6394","normalized":[]},{"id":"6402","type":"CID","arg1_id":"6373","arg2_id":"6371","normalized":[]},{"id":"6403","type":"CID","arg1_id":"6373","arg2_id":"6394","normalized":[]},{"id":"6404","type":"CID","arg1_id":"6374","arg2_id":"6371","normalized":[]},{"id":"6405","type":"CID","arg1_id":"6374","arg2_id":"6394","normalized":[]},{"id":"6406","type":"CID","arg1_id":"6375","arg2_id":"6371","normalized":[]},{"id":"6407","type":"CID","arg1_id":"6375","arg2_id":"6394","normalized":[]},{"id":"6408","type":"CID","arg1_id":"6376","arg2_id":"6371","normalized":[]},{"id":"6409","type":"CID","arg1_id":"6376","arg2_id":"6394","normalized":[]},{"id":"6410","type":"CID","arg1_id":"6378","arg2_id":"6371","normalized":[]},{"id":"6411","type":"CID","arg1_id":"6378","arg2_id":"6394","normalized":[]},{"id":"6412","type":"CID","arg1_id":"6379","arg2_id":"6371","normalized":[]},{"id":"6413","type":"CID","arg1_id":"6379","arg2_id":"6394","normalized":[]},{"id":"6414","type":"CID","arg1_id":"6381","arg2_id":"6371","normalized":[]},{"id":"6415","type":"CID","arg1_id":"6381","arg2_id":"6394","normalized":[]},{"id":"6416","type":"CID","arg1_id":"6382","arg2_id":"6371","normalized":[]},{"id":"6417","type":"CID","arg1_id":"6382","arg2_id":"6394","normalized":[]},{"id":"6418","type":"CID","arg1_id":"6383","arg2_id":"6371","normalized":[]},{"id":"6419","type":"CID","arg1_id":"6383","arg2_id":"6394","normalized":[]},{"id":"6420","type":"CID","arg1_id":"6384","arg2_id":"6371","normalized":[]},{"id":"6421","type":"CID","arg1_id":"6384","arg2_id":"6394","normalized":[]},{"id":"6422","type":"CID","arg1_id":"6388","arg2_id":"6371","normalized":[]},{"id":"6423","type":"CID","arg1_id":"6388","arg2_id":"6394","normalized":[]},{"id":"6424","type":"CID","arg1_id":"6389","arg2_id":"6371","normalized":[]},{"id":"6425","type":"CID","arg1_id":"6389","arg2_id":"6394","normalized":[]},{"id":"6426","type":"CID","arg1_id":"6391","arg2_id":"6371","normalized":[]},{"id":"6427","type":"CID","arg1_id":"6391","arg2_id":"6394","normalized":[]},{"id":"6428","type":"CID","arg1_id":"6393","arg2_id":"6371","normalized":[]},{"id":"6429","type":"CID","arg1_id":"6393","arg2_id":"6394","normalized":[]},{"id":"6430","type":"CID","arg1_id":"6395","arg2_id":"6371","normalized":[]},{"id":"6431","type":"CID","arg1_id":"6395","arg2_id":"6394","normalized":[]}]}
{"id":"6432","document_id":"2722224","passages":[{"id":"6433","type":"title","text":["Hydrocortisone-induced hypertension in humans: pressor responsiveness and sympathetic function."],"offsets":[[0,95]]},{"id":"6434","type":"abstract","text":["Oral hydrocortisone increases blood pressure and enhances pressor responsiveness in normal human subjects. We studied the effects of 1 week of oral hydrocortisone (200 mg\/day) on blood pressure, cardiac output, total peripheral resistance, forearm vascular resistance, and norepinephrine spillover to plasma in eight healthy male volunteers. Although diastolic blood pressure remained unchanged, systolic blood pressure increased from 119 to 135 mm Hg (SED +\/- 3.4, p less than 0.01), associated with an increased cardiac output (5.85-7.73 l\/min, SED +\/- 0.46, p less than 0.01). Total peripheral vascular resistance fell from 15.1 to 12.2 mm Hg\/l\/min (SED +\/- 1.03, p less than 0.05). Resting forearm vascular resistance remained unchanged, but the reflex response to the cold pressor test was accentuated, the rise in resistance increasing from 10.5 mm Hg\/ml\/100 ml\/min (R units) before treatment to 32.6 R units after treatment (SED +\/- 6.4, p less than 0.025). The rise in forearm vascular resistance accompanying intra-arterial norepinephrine (25, 50, and 100 ng\/min) was also significantly greater after hydrocortisone, increasing from an average of 14.9 +\/- 2.4 R units before treatment to 35.1 +\/- 5.5 R units after hydrocortisone (SED +\/- 6.0, p less than 0.05). A shift to the left in the dose-response relation and fall in threshold suggested increased sensitivity to norepinephrine after treatment. Measurement of resting norepinephrine spillover rate to plasma and norepinephrine uptake indicated that overall resting sympathetic nervous system activity was not increased. The rise in resting blood pressure with hydrocortisone is associated with an increased cardiac output (presumably due to increased blood volume).(ABSTRACT TRUNCATED AT 250 WORDS)"],"offsets":[[96,1860]]}],"entities":[{"id":"6435","type":"Chemical","text":["Hydrocortisone"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D006854"}]},{"id":"6436","type":"Disease","text":["hypertension"],"offsets":[[23,35]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"6437","type":"Chemical","text":["hydrocortisone"],"offsets":[[101,115]],"normalized":[{"db_name":"MESH","db_id":"D006854"}]},{"id":"6438","type":"Chemical","text":["hydrocortisone"],"offsets":[[244,258]],"normalized":[{"db_name":"MESH","db_id":"D006854"}]},{"id":"6439","type":"Chemical","text":["norepinephrine"],"offsets":[[369,383]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"6440","type":"Disease","text":["increased cardiac output"],"offsets":[[600,624]],"normalized":[{"db_name":"MESH","db_id":"D016534"}]},{"id":"6441","type":"Chemical","text":["norepinephrine"],"offsets":[[1129,1143]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"6442","type":"Chemical","text":["hydrocortisone"],"offsets":[[1206,1220]],"normalized":[{"db_name":"MESH","db_id":"D006854"}]},{"id":"6443","type":"Chemical","text":["hydrocortisone"],"offsets":[[1320,1334]],"normalized":[{"db_name":"MESH","db_id":"D006854"}]},{"id":"6444","type":"Chemical","text":["norepinephrine"],"offsets":[[1475,1489]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"6445","type":"Chemical","text":["norepinephrine"],"offsets":[[1530,1544]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"6446","type":"Chemical","text":["norepinephrine"],"offsets":[[1574,1588]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"6447","type":"Disease","text":["rise in resting blood pressure"],"offsets":[[1686,1716]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"6448","type":"Chemical","text":["hydrocortisone"],"offsets":[[1722,1736]],"normalized":[{"db_name":"MESH","db_id":"D006854"}]},{"id":"6449","type":"Disease","text":["increased cardiac output"],"offsets":[[1759,1783]],"normalized":[{"db_name":"MESH","db_id":"D016534"}]}],"events":[],"coreferences":[],"relations":[{"id":"6450","type":"CID","arg1_id":"6435","arg2_id":"6436","normalized":[]},{"id":"6451","type":"CID","arg1_id":"6435","arg2_id":"6447","normalized":[]},{"id":"6452","type":"CID","arg1_id":"6437","arg2_id":"6436","normalized":[]},{"id":"6453","type":"CID","arg1_id":"6437","arg2_id":"6447","normalized":[]},{"id":"6454","type":"CID","arg1_id":"6438","arg2_id":"6436","normalized":[]},{"id":"6455","type":"CID","arg1_id":"6438","arg2_id":"6447","normalized":[]},{"id":"6456","type":"CID","arg1_id":"6442","arg2_id":"6436","normalized":[]},{"id":"6457","type":"CID","arg1_id":"6442","arg2_id":"6447","normalized":[]},{"id":"6458","type":"CID","arg1_id":"6443","arg2_id":"6436","normalized":[]},{"id":"6459","type":"CID","arg1_id":"6443","arg2_id":"6447","normalized":[]},{"id":"6460","type":"CID","arg1_id":"6448","arg2_id":"6436","normalized":[]},{"id":"6461","type":"CID","arg1_id":"6448","arg2_id":"6447","normalized":[]}]}
{"id":"6462","document_id":"1636026","passages":[{"id":"6463","type":"title","text":["Effects of suprofen on the isolated perfused rat kidney."],"offsets":[[0,56]]},{"id":"6464","type":"abstract","text":["Although suprofen has been associated with the development of acute renal failure in greater than 100 subjects, the mechanism of damage remains unclear. The direct nephrotoxic effects of a single dose of 15 mg of suprofen were compared in the recirculating isolated rat kidney perfused with cell-free buffer with or without the addition of 5 mg\/dL of uric acid. There were no significant differences in renal sodium excretion, oxygen consumption, or urinary flow rates in kidneys perfused with suprofen compared with the drug-free control groups. In contrast, a significant decline in glomerular filtration rate was found after the introduction of suprofen to the kidney perfused with uric acid; no changes were found with suprofen in the absence of uric acid. A significant decrease in the baseline excretion rate of uric acid was found in rats given suprofen, compared with drug-free controls. However, the fractional excretion of uric acid was unchanged between the groups over the experimental period. In summary, suprofen causes acute declines in renal function, most likely by directly altering the intrarenal distribution of uric acid."],"offsets":[[57,1199]]}],"entities":[{"id":"6465","type":"Chemical","text":["suprofen"],"offsets":[[11,19]],"normalized":[{"db_name":"MESH","db_id":"D013496"}]},{"id":"6466","type":"Chemical","text":["suprofen"],"offsets":[[66,74]],"normalized":[{"db_name":"MESH","db_id":"D013496"}]},{"id":"6467","type":"Disease","text":["acute renal failure"],"offsets":[[119,138]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"6468","type":"Disease","text":["nephrotoxic"],"offsets":[[221,232]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"6469","type":"Chemical","text":["suprofen"],"offsets":[[270,278]],"normalized":[{"db_name":"MESH","db_id":"D013496"}]},{"id":"6470","type":"Chemical","text":["uric acid"],"offsets":[[408,417]],"normalized":[{"db_name":"MESH","db_id":"D014527"}]},{"id":"6471","type":"Chemical","text":["sodium"],"offsets":[[466,472]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"6472","type":"Chemical","text":["oxygen"],"offsets":[[484,490]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"6473","type":"Chemical","text":["suprofen"],"offsets":[[551,559]],"normalized":[{"db_name":"MESH","db_id":"D013496"}]},{"id":"6474","type":"Chemical","text":["suprofen"],"offsets":[[705,713]],"normalized":[{"db_name":"MESH","db_id":"D013496"}]},{"id":"6475","type":"Chemical","text":["uric acid"],"offsets":[[742,751]],"normalized":[{"db_name":"MESH","db_id":"D014527"}]},{"id":"6476","type":"Chemical","text":["suprofen"],"offsets":[[780,788]],"normalized":[{"db_name":"MESH","db_id":"D013496"}]},{"id":"6477","type":"Chemical","text":["uric acid"],"offsets":[[807,816]],"normalized":[{"db_name":"MESH","db_id":"D014527"}]},{"id":"6478","type":"Chemical","text":["uric acid"],"offsets":[[875,884]],"normalized":[{"db_name":"MESH","db_id":"D014527"}]},{"id":"6479","type":"Chemical","text":["suprofen"],"offsets":[[909,917]],"normalized":[{"db_name":"MESH","db_id":"D013496"}]},{"id":"6480","type":"Chemical","text":["uric acid"],"offsets":[[990,999]],"normalized":[{"db_name":"MESH","db_id":"D014527"}]},{"id":"6481","type":"Chemical","text":["suprofen"],"offsets":[[1075,1083]],"normalized":[{"db_name":"MESH","db_id":"D013496"}]},{"id":"6482","type":"Disease","text":["acute declines in renal function"],"offsets":[[1091,1123]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"6483","type":"Chemical","text":["uric acid"],"offsets":[[1189,1198]],"normalized":[{"db_name":"MESH","db_id":"D014527"}]}],"events":[],"coreferences":[],"relations":[{"id":"6484","type":"CID","arg1_id":"6465","arg2_id":"6467","normalized":[]},{"id":"6485","type":"CID","arg1_id":"6465","arg2_id":"6482","normalized":[]},{"id":"6486","type":"CID","arg1_id":"6466","arg2_id":"6467","normalized":[]},{"id":"6487","type":"CID","arg1_id":"6466","arg2_id":"6482","normalized":[]},{"id":"6488","type":"CID","arg1_id":"6469","arg2_id":"6467","normalized":[]},{"id":"6489","type":"CID","arg1_id":"6469","arg2_id":"6482","normalized":[]},{"id":"6490","type":"CID","arg1_id":"6473","arg2_id":"6467","normalized":[]},{"id":"6491","type":"CID","arg1_id":"6473","arg2_id":"6482","normalized":[]},{"id":"6492","type":"CID","arg1_id":"6474","arg2_id":"6467","normalized":[]},{"id":"6493","type":"CID","arg1_id":"6474","arg2_id":"6482","normalized":[]},{"id":"6494","type":"CID","arg1_id":"6476","arg2_id":"6467","normalized":[]},{"id":"6495","type":"CID","arg1_id":"6476","arg2_id":"6482","normalized":[]},{"id":"6496","type":"CID","arg1_id":"6479","arg2_id":"6467","normalized":[]},{"id":"6497","type":"CID","arg1_id":"6479","arg2_id":"6482","normalized":[]},{"id":"6498","type":"CID","arg1_id":"6481","arg2_id":"6467","normalized":[]},{"id":"6499","type":"CID","arg1_id":"6481","arg2_id":"6482","normalized":[]}]}
{"id":"6500","document_id":"1610717","passages":[{"id":"6501","type":"title","text":["Cocaine-induced brainstem seizures and behavior."],"offsets":[[0,48]]},{"id":"6502","type":"abstract","text":["A variety of abnormal sensory\/motor behaviors associated with electrical discharges recorded from the bilateral brainstem were induced in adult WKY rats by mechanical (electrode implants) and DC electrical current stimulations and by acute and chronic administration of cocaine. The electrode implant implicated one side or the other of the reticular system of the brainstem but subjects were not incapacitated by the stimulations. Cocaine (40 mg\/kg) was injected subcutaneously for an acute experiment and subsequent 20 mg\/kg doses twice daily for 3 days in a chronic study. Cocaine generated more abnormal behaviors in the brainstem perturbation group, especially the electrically perturbated subjects. The abnormal behaviors were yawning, retrocollis, hyperactivity, hypersensitivity, \"beating drum\" behavior, squealing, head bobbing, circling, sniffing, abnormal posturing, and facial twitching. Shifts in the power frequency spectra of the discharge patterns were noted between quiet and pacing behavioral states. Hypersensitivity to various auditory, tactile, and visual stimulation was present and shifts in the brainstem ambient power spectral frequency occurred in response to tactile stimulation. These findings suggest that the brainstem generates and propagates pathological discharges that can be elicited by mechanical and DC electrical perturbation. Cocaine was found to activate the discharge system and thus induce abnormal behaviors that are generated at the discharge site and at distant sites to which the discharge propagates. Cognitive functions may also be involved since dopaminergic and serotonergic cellular elements at the brainstem level are also implicated."],"offsets":[[49,1735]]}],"entities":[{"id":"6503","type":"Chemical","text":["Cocaine"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6504","type":"Disease","text":["seizures"],"offsets":[[26,34]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"6505","type":"Chemical","text":["cocaine"],"offsets":[[319,326]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6506","type":"Chemical","text":["Cocaine"],"offsets":[[481,488]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6507","type":"Chemical","text":["Cocaine"],"offsets":[[625,632]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"6508","type":"Disease","text":["hyperactivity"],"offsets":[[804,817]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"6509","type":"Disease","text":["hypersensitivity"],"offsets":[[819,835]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"6510","type":"Disease","text":["Hypersensitivity"],"offsets":[[1068,1084]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"6511","type":"Chemical","text":["Cocaine"],"offsets":[[1414,1421]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]}],"events":[],"coreferences":[],"relations":[{"id":"6512","type":"CID","arg1_id":"6503","arg2_id":"6504","normalized":[]},{"id":"6513","type":"CID","arg1_id":"6505","arg2_id":"6504","normalized":[]},{"id":"6514","type":"CID","arg1_id":"6506","arg2_id":"6504","normalized":[]},{"id":"6515","type":"CID","arg1_id":"6507","arg2_id":"6504","normalized":[]},{"id":"6516","type":"CID","arg1_id":"6511","arg2_id":"6504","normalized":[]}]}
{"id":"6517","document_id":"873132","passages":[{"id":"6518","type":"title","text":["Increased sulfation and decreased 7alpha-hydroxylation of deoxycholic acid in ethinyl estradiol-induced cholestasis in rats."],"offsets":[[0,124]]},{"id":"6519","type":"abstract","text":["Deoxycholic acid conjugation, transport capacity, and metabolism were compared in control and ethinyl estradiol-treated rats. Control rats were found to have a lower capacity to transport deoxycholic acid than taurodeoxycholic acid, and both were decreased by ethinyl estradiol treatment. During [24-14C]sodium deoxycholate infusion, [14C]biliary bile acid secretion increased, but bile flow did not change significantly in either control or ethinyl estradiol-treated rats. Ethinyl estradiol-treated animals excreted significantly less 14C as taurocholic acid than did control animals, consistent with an impairment of 7alpha-hydroxylation of taurodeoxycholic acid. Ethinyl estradiol treatment did not impair conjugation of deoxycholic acid, but did result in an increase in sulfation of taurodeoxycholic acid from 1.5% in controls to nearly 4.0% (P less than 0.01). These results are consistent with the hypothesis that the rat has a poorer tolerance for deoxycholic acid than do certain other species. Furthermore, the rat converts deoxycholic acid, a poor choleretic, to taurocholic acid, a good choleretic. When this conversion is impaired with ethinyl estradiol treatment, sulfation may be an important alternate pathway for excretion of this potentially harmful bile acid."],"offsets":[[125,1403]]}],"entities":[{"id":"6520","type":"Chemical","text":["deoxycholic acid"],"offsets":[[58,74]],"normalized":[{"db_name":"MESH","db_id":"D003840"}]},{"id":"6521","type":"Chemical","text":["ethinyl estradiol"],"offsets":[[78,95]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"6522","type":"Disease","text":["cholestasis"],"offsets":[[104,115]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"6523","type":"Chemical","text":["Deoxycholic acid"],"offsets":[[125,141]],"normalized":[{"db_name":"MESH","db_id":"D003840"}]},{"id":"6524","type":"Chemical","text":["ethinyl estradiol"],"offsets":[[219,236]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"6525","type":"Chemical","text":["deoxycholic acid"],"offsets":[[313,329]],"normalized":[{"db_name":"MESH","db_id":"D003840"}]},{"id":"6526","type":"Chemical","text":["taurodeoxycholic acid"],"offsets":[[335,356]],"normalized":[{"db_name":"MESH","db_id":"D013657"}]},{"id":"6527","type":"Chemical","text":["ethinyl estradiol"],"offsets":[[385,402]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"6528","type":"Chemical","text":["sodium deoxycholate"],"offsets":[[429,448]],"normalized":[{"db_name":"MESH","db_id":"D003840"}]},{"id":"6529","type":"Chemical","text":["bile acid"],"offsets":[[472,481]],"normalized":[{"db_name":"MESH","db_id":"D001647"}]},{"id":"6530","type":"Chemical","text":["ethinyl estradiol"],"offsets":[[567,584]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"6531","type":"Chemical","text":["Ethinyl estradiol"],"offsets":[[599,616]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"6532","type":"Chemical","text":["taurocholic acid"],"offsets":[[668,684]],"normalized":[{"db_name":"MESH","db_id":"D013656"}]},{"id":"6533","type":"Chemical","text":["taurodeoxycholic acid"],"offsets":[[768,789]],"normalized":[{"db_name":"MESH","db_id":"D013657"}]},{"id":"6534","type":"Chemical","text":["Ethinyl estradiol"],"offsets":[[791,808]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"6535","type":"Chemical","text":["deoxycholic acid"],"offsets":[[849,865]],"normalized":[{"db_name":"MESH","db_id":"D003840"}]},{"id":"6536","type":"Chemical","text":["taurodeoxycholic acid"],"offsets":[[913,934]],"normalized":[{"db_name":"MESH","db_id":"D013657"}]},{"id":"6537","type":"Chemical","text":["deoxycholic acid"],"offsets":[[1081,1097]],"normalized":[{"db_name":"MESH","db_id":"D003840"}]},{"id":"6538","type":"Chemical","text":["deoxycholic acid"],"offsets":[[1159,1175]],"normalized":[{"db_name":"MESH","db_id":"D003840"}]},{"id":"6539","type":"Chemical","text":["taurocholic acid"],"offsets":[[1199,1215]],"normalized":[{"db_name":"MESH","db_id":"D013656"}]},{"id":"6540","type":"Chemical","text":["ethinyl estradiol"],"offsets":[[1274,1291]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"6541","type":"Chemical","text":["bile acid"],"offsets":[[1393,1402]],"normalized":[{"db_name":"MESH","db_id":"D001647"}]}],"events":[],"coreferences":[],"relations":[{"id":"6542","type":"CID","arg1_id":"6521","arg2_id":"6522","normalized":[]},{"id":"6543","type":"CID","arg1_id":"6524","arg2_id":"6522","normalized":[]},{"id":"6544","type":"CID","arg1_id":"6527","arg2_id":"6522","normalized":[]},{"id":"6545","type":"CID","arg1_id":"6530","arg2_id":"6522","normalized":[]},{"id":"6546","type":"CID","arg1_id":"6531","arg2_id":"6522","normalized":[]},{"id":"6547","type":"CID","arg1_id":"6534","arg2_id":"6522","normalized":[]},{"id":"6548","type":"CID","arg1_id":"6540","arg2_id":"6522","normalized":[]}]}
{"id":"6549","document_id":"783197","passages":[{"id":"6550","type":"title","text":["Effects of ouabain on myocardial oxygen supply and demand in patients with chronic coronary artery disease. A hemodynamic, volumetric, and metabolic study in patients without heart failure."],"offsets":[[0,189]]},{"id":"6551","type":"abstract","text":["The effects of digitalis glycosides on myocardial oxygen supply and demand are of particular interest in the presence of obstructive coronary artery disease, but have not been measured previously in man. We assessed the effects of ouabain (0.015 mg\/kg body weight) on hemodynamic, volumetric, and metabolic parameters in 11 patients with severe chronic coronary artery disease without clinical congestive heart failure. Because the protocol was long and involved interventions which might affect the determinations, we also studied in nine patients using an identical protocol except that ouabain administration was omitted. Left ventricular end-diastolic pressure and left ventricular end-diastolic volume fell in each patient given ouabain, even though they were initially elevated in only two patients. Left ventricular end-diastolic pressure fell from 11.5+\/-1.4 (mean+\/-SE) to 5.6+\/-0.9 mm Hg (P less than 0.001) and left ventricular end-diastolic volume fell from 100+\/-17 to 82+\/-12 ml\/m2 (P less than 0.01) 1 h after ouabain infusion was completed. The maximum velocity of contractile element shortening increased from 1.68+\/-0.11 ml\/s to 2.18+\/-0.21 muscle-lengths\/s (P less than 0.05) and is consistent with an increase in contractility. No significant change in these parameters occurred in the control patients. No significant change in myocardial oxygen consumption occurred after ouabain administration but this may be related to a greater decrease in mean arterial pressure in the ouabain patients than in the control patients. We conclude that in patients with chronic coronary artery disease who are not in clinical congestive heart failure left ventricular end-diastolic volume falls after ouabain administration even when it is initially normal. Though this fall would be associated with a decrease in wall tension, and, therefore, of myocardial oxygen consumption, it may not be of sufficient magnitude to prevent a net increase in myocardial oxygen consumption. Nevertheless, compensatory mechanisms prevent a deterioration of resting myocardial metabolism."],"offsets":[[190,2268]]}],"entities":[{"id":"6552","type":"Chemical","text":["ouabain"],"offsets":[[11,18]],"normalized":[{"db_name":"MESH","db_id":"D010042"}]},{"id":"6553","type":"Chemical","text":["oxygen"],"offsets":[[33,39]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"6554","type":"Disease","text":["coronary artery disease"],"offsets":[[83,106]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"6555","type":"Disease","text":["heart failure"],"offsets":[[175,188]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"6556","type":"Chemical","text":["digitalis glycosides"],"offsets":[[205,225]],"normalized":[{"db_name":"MESH","db_id":"D004071"}]},{"id":"6557","type":"Chemical","text":["oxygen"],"offsets":[[240,246]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"6558","type":"Disease","text":["coronary artery disease"],"offsets":[[323,346]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"6559","type":"Chemical","text":["ouabain"],"offsets":[[421,428]],"normalized":[{"db_name":"MESH","db_id":"D010042"}]},{"id":"6560","type":"Disease","text":["coronary artery disease"],"offsets":[[543,566]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"6561","type":"Disease","text":["congestive heart failure"],"offsets":[[584,608]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"6562","type":"Chemical","text":["ouabain"],"offsets":[[779,786]],"normalized":[{"db_name":"MESH","db_id":"D010042"}]},{"id":"6563","type":"Chemical","text":["ouabain"],"offsets":[[924,931]],"normalized":[{"db_name":"MESH","db_id":"D010042"}]},{"id":"6564","type":"Chemical","text":["ouabain"],"offsets":[[1215,1222]],"normalized":[{"db_name":"MESH","db_id":"D010042"}]},{"id":"6565","type":"Chemical","text":["oxygen"],"offsets":[[1550,1556]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"6566","type":"Chemical","text":["ouabain"],"offsets":[[1584,1591]],"normalized":[{"db_name":"MESH","db_id":"D010042"}]},{"id":"6567","type":"Chemical","text":["ouabain"],"offsets":[[1686,1693]],"normalized":[{"db_name":"MESH","db_id":"D010042"}]},{"id":"6568","type":"Disease","text":["coronary artery disease"],"offsets":[[1775,1798]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"6569","type":"Disease","text":["congestive heart failure"],"offsets":[[1823,1847]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"6570","type":"Disease","text":["left ventricular end-diastolic volume falls"],"offsets":[[1848,1891]],"normalized":[{"db_name":"MESH","db_id":"D002303"}]},{"id":"6571","type":"Chemical","text":["ouabain"],"offsets":[[1898,1905]],"normalized":[{"db_name":"MESH","db_id":"D010042"}]},{"id":"6572","type":"Chemical","text":["oxygen"],"offsets":[[2055,2061]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"6573","type":"Chemical","text":["oxygen"],"offsets":[[2153,2159]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]}],"events":[],"coreferences":[],"relations":[{"id":"6574","type":"CID","arg1_id":"6552","arg2_id":"6570","normalized":[]},{"id":"6575","type":"CID","arg1_id":"6559","arg2_id":"6570","normalized":[]},{"id":"6576","type":"CID","arg1_id":"6562","arg2_id":"6570","normalized":[]},{"id":"6577","type":"CID","arg1_id":"6563","arg2_id":"6570","normalized":[]},{"id":"6578","type":"CID","arg1_id":"6564","arg2_id":"6570","normalized":[]},{"id":"6579","type":"CID","arg1_id":"6566","arg2_id":"6570","normalized":[]},{"id":"6580","type":"CID","arg1_id":"6567","arg2_id":"6570","normalized":[]},{"id":"6581","type":"CID","arg1_id":"6571","arg2_id":"6570","normalized":[]}]}
{"id":"6582","document_id":"9545159","passages":[{"id":"6583","type":"title","text":["Prolongation of the QT interval related to cisapride-diltiazem interaction."],"offsets":[[0,75]]},{"id":"6584","type":"abstract","text":["Cisapride, a cytochrome P450 3A4 (CYP3A4) substrate, is widely prescribed for the treatment of gastrointestinal motility disorders. Prolongation of QT interval, torsades de pointes, and sudden cardiac death have been reported after concomitant administration with erythromycin or azole antifungal agents, but not with other CYP3A4 inhibitors. A possible drug interaction occurred in a 45-year-old woman who was taking cisapride for gastroesophageal reflux disorder and diltiazem, an agent that has inhibitory effect on CYP3A4, for hypertension. The patient was in near syncope and had QT-interval prolongation. After discontinuing cisapride, the QT interval returned to normal and symptoms did not recur. We suggest that caution be taken when cisapride is prescribed with any potent inhibitor of CYP3A4, including diltiazem."],"offsets":[[76,900]]}],"entities":[{"id":"6585","type":"Disease","text":["Prolongation of the QT interval"],"offsets":[[0,31]],"normalized":[{"db_name":"MESH","db_id":"D008133"}]},{"id":"6586","type":"Chemical","text":["cisapride"],"offsets":[[43,52]],"normalized":[{"db_name":"MESH","db_id":"D020117"}]},{"id":"6587","type":"Chemical","text":["diltiazem"],"offsets":[[53,62]],"normalized":[{"db_name":"MESH","db_id":"D004110"}]},{"id":"6588","type":"Chemical","text":["Cisapride"],"offsets":[[76,85]],"normalized":[{"db_name":"MESH","db_id":"D020117"}]},{"id":"6589","type":"Disease","text":["gastrointestinal motility disorders"],"offsets":[[171,206]],"normalized":[{"db_name":"MESH","db_id":"D015835"}]},{"id":"6590","type":"Disease","text":["Prolongation of QT interval"],"offsets":[[208,235]],"normalized":[{"db_name":"MESH","db_id":"D008133"}]},{"id":"6591","type":"Disease","text":["torsades de pointes"],"offsets":[[237,256]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"6592","type":"Disease","text":["sudden cardiac death"],"offsets":[[262,282]],"normalized":[{"db_name":"MESH","db_id":"D016757"}]},{"id":"6593","type":"Chemical","text":["erythromycin"],"offsets":[[340,352]],"normalized":[{"db_name":"MESH","db_id":"D004917"}]},{"id":"6594","type":"Chemical","text":["azole"],"offsets":[[356,361]],"normalized":[{"db_name":"MESH","db_id":"D001393"}]},{"id":"6595","type":"Chemical","text":["cisapride"],"offsets":[[494,503]],"normalized":[{"db_name":"MESH","db_id":"D020117"}]},{"id":"6596","type":"Disease","text":["gastroesophageal reflux disorder"],"offsets":[[508,540]],"normalized":[{"db_name":"MESH","db_id":"D005764"}]},{"id":"6597","type":"Chemical","text":["diltiazem"],"offsets":[[545,554]],"normalized":[{"db_name":"MESH","db_id":"D004110"}]},{"id":"6598","type":"Disease","text":["hypertension"],"offsets":[[607,619]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"6599","type":"Disease","text":["syncope"],"offsets":[[645,652]],"normalized":[{"db_name":"MESH","db_id":"D013575"}]},{"id":"6600","type":"Disease","text":["QT-interval prolongation"],"offsets":[[661,685]],"normalized":[{"db_name":"MESH","db_id":"D008133"}]},{"id":"6601","type":"Chemical","text":["cisapride"],"offsets":[[707,716]],"normalized":[{"db_name":"MESH","db_id":"D020117"}]},{"id":"6602","type":"Chemical","text":["cisapride"],"offsets":[[819,828]],"normalized":[{"db_name":"MESH","db_id":"D020117"}]},{"id":"6603","type":"Chemical","text":["diltiazem"],"offsets":[[890,899]],"normalized":[{"db_name":"MESH","db_id":"D004110"}]}],"events":[],"coreferences":[],"relations":[{"id":"6604","type":"CID","arg1_id":"6594","arg2_id":"6592","normalized":[]},{"id":"6605","type":"CID","arg1_id":"6594","arg2_id":"6585","normalized":[]},{"id":"6606","type":"CID","arg1_id":"6594","arg2_id":"6590","normalized":[]},{"id":"6607","type":"CID","arg1_id":"6594","arg2_id":"6600","normalized":[]},{"id":"6608","type":"CID","arg1_id":"6587","arg2_id":"6585","normalized":[]},{"id":"6609","type":"CID","arg1_id":"6587","arg2_id":"6590","normalized":[]},{"id":"6610","type":"CID","arg1_id":"6587","arg2_id":"6600","normalized":[]},{"id":"6611","type":"CID","arg1_id":"6597","arg2_id":"6585","normalized":[]},{"id":"6612","type":"CID","arg1_id":"6597","arg2_id":"6590","normalized":[]},{"id":"6613","type":"CID","arg1_id":"6597","arg2_id":"6600","normalized":[]},{"id":"6614","type":"CID","arg1_id":"6603","arg2_id":"6585","normalized":[]},{"id":"6615","type":"CID","arg1_id":"6603","arg2_id":"6590","normalized":[]},{"id":"6616","type":"CID","arg1_id":"6603","arg2_id":"6600","normalized":[]},{"id":"6617","type":"CID","arg1_id":"6594","arg2_id":"6591","normalized":[]},{"id":"6618","type":"CID","arg1_id":"6586","arg2_id":"6592","normalized":[]},{"id":"6619","type":"CID","arg1_id":"6588","arg2_id":"6592","normalized":[]},{"id":"6620","type":"CID","arg1_id":"6595","arg2_id":"6592","normalized":[]},{"id":"6621","type":"CID","arg1_id":"6601","arg2_id":"6592","normalized":[]},{"id":"6622","type":"CID","arg1_id":"6602","arg2_id":"6592","normalized":[]},{"id":"6623","type":"CID","arg1_id":"6593","arg2_id":"6591","normalized":[]},{"id":"6624","type":"CID","arg1_id":"6593","arg2_id":"6585","normalized":[]},{"id":"6625","type":"CID","arg1_id":"6593","arg2_id":"6590","normalized":[]},{"id":"6626","type":"CID","arg1_id":"6593","arg2_id":"6600","normalized":[]},{"id":"6627","type":"CID","arg1_id":"6586","arg2_id":"6585","normalized":[]},{"id":"6628","type":"CID","arg1_id":"6586","arg2_id":"6590","normalized":[]},{"id":"6629","type":"CID","arg1_id":"6586","arg2_id":"6600","normalized":[]},{"id":"6630","type":"CID","arg1_id":"6588","arg2_id":"6585","normalized":[]},{"id":"6631","type":"CID","arg1_id":"6588","arg2_id":"6590","normalized":[]},{"id":"6632","type":"CID","arg1_id":"6588","arg2_id":"6600","normalized":[]},{"id":"6633","type":"CID","arg1_id":"6595","arg2_id":"6585","normalized":[]},{"id":"6634","type":"CID","arg1_id":"6595","arg2_id":"6590","normalized":[]},{"id":"6635","type":"CID","arg1_id":"6595","arg2_id":"6600","normalized":[]},{"id":"6636","type":"CID","arg1_id":"6601","arg2_id":"6585","normalized":[]},{"id":"6637","type":"CID","arg1_id":"6601","arg2_id":"6590","normalized":[]},{"id":"6638","type":"CID","arg1_id":"6601","arg2_id":"6600","normalized":[]},{"id":"6639","type":"CID","arg1_id":"6602","arg2_id":"6585","normalized":[]},{"id":"6640","type":"CID","arg1_id":"6602","arg2_id":"6590","normalized":[]},{"id":"6641","type":"CID","arg1_id":"6602","arg2_id":"6600","normalized":[]},{"id":"6642","type":"CID","arg1_id":"6586","arg2_id":"6591","normalized":[]},{"id":"6643","type":"CID","arg1_id":"6588","arg2_id":"6591","normalized":[]},{"id":"6644","type":"CID","arg1_id":"6595","arg2_id":"6591","normalized":[]},{"id":"6645","type":"CID","arg1_id":"6601","arg2_id":"6591","normalized":[]},{"id":"6646","type":"CID","arg1_id":"6602","arg2_id":"6591","normalized":[]},{"id":"6647","type":"CID","arg1_id":"6593","arg2_id":"6592","normalized":[]}]}
{"id":"6648","document_id":"8643973","passages":[{"id":"6649","type":"title","text":["Paclitaxel combined with carboplatin in the first-line treatment of advanced ovarian cancer."],"offsets":[[0,92]]},{"id":"6650","type":"abstract","text":["In a phase I study to determine the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given as a 3-hour infusion in combination with carboplatin administered every 21 days to women with advanced ovarian cancer, paclitaxel doses were escalated as follows: level 1, 135 mg\/m2; level 2, 160 mg\/m2; level 3, 185 mg\/m2; and level 4,210 mg\/m2. The fixed dose of carboplatin at levels 1 through 4 was given to achieve an area under the concentration-time curve (AUC) of 5 using the Calvert formula. In levels 5 and 6 the carboplatin dose was targeted at AUCs of 6 and 7.5, respectively, combined with a fixed paclitaxel dose of 185 mg\/m2. To date, 30 previously untreated patients, all with a good performance status (Eastern Cooperative Oncology Group 0 to 2) have been entered into this ongoing study. The dose-limiting toxicity of the combination was myelosuppression (leukopenia, granulocytopenia, and thrombocytopenia). Neurotoxicity was largely moderate. So far, 14 patients are evaluable for response; of these, eight (57%) showed objective (complete or partial) response and disease stabilized in six patients. No patient had disease progression. We conclude that the combination of paclitaxel 185 mg\/m2 administered as a 3-hour infusion followed immediately by a 1-hour infusion of carboplatin at an AUC of 6 can be administered safely in a 21-day schedule in the outpatient setting. The recommended dose for phase III studies is paclitaxel 185 mg\/m2 and carboplatin AUC 6."],"offsets":[[93,1608]]}],"entities":[{"id":"6651","type":"Chemical","text":["Paclitaxel"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"6652","type":"Chemical","text":["carboplatin"],"offsets":[[25,36]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"6653","type":"Disease","text":["ovarian cancer"],"offsets":[[77,91]],"normalized":[{"db_name":"MESH","db_id":"D010051"}]},{"id":"6654","type":"Chemical","text":["paclitaxel"],"offsets":[[155,165]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"6655","type":"Chemical","text":["Taxol"],"offsets":[[167,172]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"6656","type":"Chemical","text":["carboplatin"],"offsets":[[266,277]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"6657","type":"Disease","text":["ovarian 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{"id":"6724","document_id":"10743694","passages":[{"id":"6725","type":"title","text":["Treatment of tacrolimus-related adverse effects by conversion to cyclosporine in liver transplant recipients."],"offsets":[[0,109]]},{"id":"6726","type":"abstract","text":["When tacrolimus side effects persist despite dose reduction, conversion to cyclosporine-based immunosuppression (CyA) is necessary. We characterized tacrolimus side effects that warranted discontinuation of the drug, and outcomes after conversion. Of 388 liver recipients who received tacrolimus as primary immunosuppression, 70 required conversion to CyA. We recorded indication for conversion, whether conversion was early or late after transplantation, tacrolimus dose and trough blood level at conversion, and incidence of rejection after conversion. Conversion was early in 29 patients (41.4%) and late in 41 (58.6%). Indications for early conversion were neurotoxicity (20), (insulin-dependent) diabetes mellitus (IDDM) (5), nephrotoxicity (3), gastrointestinal (GI) toxicity (6), and cardiomyopathy (1), and for late conversion were neurotoxicity (15), IDDM (12), nephrotoxicity (3), GI toxicity (5), hepatotoxicity (6), post-transplant lmphoproliferate disease (PTLD) (2), cardiomyopathy (1), hemolytic anemia (1), and pruritus (1). All early-conversion patients showed improvement\/resolution of symptoms. Among late-conversion patients, 37 (90.2%) had improvement\/resolution; in 4 (9.8%), adverse effects persisted. The overall rejection rate was 30%. Sixty-two patients (88.6%) are alive with functioning grafts 686 +\/- 362 days (range, 154-1433 days) after conversion. When tacrolimus side effects are unresponsive to dose reduction, conversion to CyA can be accomplished safely, with no increased risk of rejection and excellent long-term outcome."],"offsets":[[110,1669]]}],"entities":[{"id":"6727","type":"Chemical","text":["tacrolimus"],"offsets":[[13,23]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"6728","type":"Chemical","text":["cyclosporine"],"offsets":[[65,77]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"6729","type":"Chemical","text":["tacrolimus"],"offsets":[[115,125]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"6730","type":"Chemical","text":["cyclosporine"],"offsets":[[185,197]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"6731","type":"Chemical","text":["tacrolimus"],"offsets":[[259,269]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"6732","type":"Chemical","text":["tacrolimus"],"offsets":[[395,405]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"6733","type":"Chemical","text":["tacrolimus"],"offsets":[[566,576]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"6734","type":"Disease","text":["neurotoxicity"],"offsets":[[771,784]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"6735","type":"Disease","text":["(insulin-dependent) diabetes mellitus"],"offsets":[[791,828]],"normalized":[{"db_name":"MESH","db_id":"D003922"}]},{"id":"6736","type":"Disease","text":["IDDM"],"offsets":[[830,834]],"normalized":[{"db_name":"MESH","db_id":"D003922"}]},{"id":"6737","type":"Disease","text":["nephrotoxicity"],"offsets":[[841,855]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"6738","type":"Disease","text":["gastrointestinal (GI) 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{"id":"6847","document_id":"3535719","passages":[{"id":"6848","type":"title","text":["Relative efficacy and toxicity of netilmicin and tobramycin in oncology patients."],"offsets":[[0,81]]},{"id":"6849","type":"abstract","text":["We prospectively compared the efficacy and safety of netilmicin sulfate or tobramycin sulfate in conjunction with piperacillin sodium in 118 immunocompromised patients with presumed severe infections. The two treatment regimens were equally efficacious. Nephrotoxicity occurred in a similar proportion in patients treated with netilmicin and tobramycin (17% vs 11%). Ototoxicity occurred in four (9.5%) of 42 netilmicin and piperacillin and in 12 (22%) of 54 tobramycin and piperacillin-treated patients. Of those evaluated with posttherapy audiograms, three of four netilmicin and piperacillin-treated patients had auditory thresholds return to baseline compared with one of nine tobramycin and piperacillin-treated patients. The number of greater than or equal to 15-dB increases in auditory threshold as a proportion of total greater than or equal to 15-dB changes (increases and decreases) was significantly lower in netilmicin and piperacillin- vs tobramycin and piperacillin-treated patients (18 of 78 vs 67 of 115). We conclude that aminoglycoside-associated ototoxicity was less severe and more often reversible with netilmicin than with tobramycin."],"offsets":[[82,1239]]}],"entities":[{"id":"6850","type":"Disease","text":["toxicity"],"offsets":[[22,30]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"6851","type":"Chemical","text":["netilmicin"],"offsets":[[34,44]],"normalized":[{"db_name":"MESH","db_id":"D009428"}]},{"id":"6852","type":"Chemical","text":["tobramycin"],"offsets":[[49,59]],"normalized":[{"db_name":"MESH","db_id":"D014031"}]},{"id":"6853","type":"Chemical","text":["netilmicin sulfate"],"offsets":[[135,153]],"normalized":[{"db_name":"MESH","db_id":"D009428"}]},{"id":"6854","type":"Chemical","text":["tobramycin sulfate"],"offsets":[[157,175]],"normalized":[{"db_name":"MESH","db_id":"D014031"}]},{"id":"6855","type":"Chemical","text":["piperacillin 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These results suggest that PGs are involved in the mechanism(s) underlying fluorthyl- and PTZ-induced convulsions, but not picrotoxin-, electroshock-, or bicuculline-induced convulsions."],"offsets":[[93,767]]}],"entities":[{"id":"6943","type":"Chemical","text":["prostaglandin"],"offsets":[[10,23]],"normalized":[{"db_name":"MESH","db_id":"D011453"}]},{"id":"6944","type":"Disease","text":["convulsions"],"offsets":[[72,83]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"6945","type":"Chemical","text":["prostaglandins"],"offsets":[[128,142]],"normalized":[{"db_name":"MESH","db_id":"D011453"}]},{"id":"6946","type":"Chemical","text":["PGs"],"offsets":[[144,147]],"normalized":[{"db_name":"MESH","db_id":"D011453"}]},{"id":"6947","type":"Disease","text":["seizure"],"offsets":[[152,159]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"6948","type":"Disease","text":["convulsions"],"offsets":[[218,229]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"6949","type":"Chemical","text":["flurothyl"],"offsets":[[241,250]],"normalized":[{"db_name":"MESH","db_id":"D005481"}]},{"id":"6950","type":"Chemical","text":["picrotoxin"],"offsets":[[252,262]],"normalized":[{"db_name":"MESH","db_id":"D010852"}]},{"id":"6951","type":"Chemical","text":["pentetrazol"],"offsets":[[264,275]],"normalized":[{"db_name":"MESH","db_id":"D010433"}]},{"id":"6952","type":"Chemical","text":["PTZ"],"offsets":[[277,280]],"normalized":[{"db_name":"MESH","db_id":"D010433"}]},{"id":"6953","type":"Chemical","text":["bicuculline"],"offsets":[[299,310]],"normalized":[{"db_name":"MESH","db_id":"D001640"}]},{"id":"6954","type":"Chemical","text":["Ibuprofen"],"offsets":[[327,336]],"normalized":[{"db_name":"MESH","db_id":"D007052"}]},{"id":"6955","type":"Chemical","text":["sulindac"],"offsets":[[338,346]],"normalized":[{"db_name":"MESH","db_id":"D013467"}]},{"id":"6956","type":"Chemical","text":["mefenamic 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{"id":"7034","document_id":"17285209","passages":[{"id":"7035","type":"title","text":["Angiotensin-converting enzyme (ACE) inhibitor-associated angioedema of the stomach and small intestine: a case report."],"offsets":[[0,118]]},{"id":"7036","type":"abstract","text":["This is a case report on a 45-year old African-American female with newly diagnosed hypertension, who was started on a combination pill of amlodipine\/benazapril 10\/5 mg. The very next day, she presented at the emergency room (ER) with abdominal pain, nausea and vomiting. Physical exam, complete metabolic panel, and hemogram were in the normal range. She was discharged from the ER after a few hours of treatment with fluid and analgesics. However, she returned to the ER the next day with the same complaints. This time the physical exam was significant for a distended abdomen with dullness to percussion. CT scan of the abdomen revealed markedly thickened antrum of the stomach, duodenum and jejunum, along with fluid in the abdominal and pelvic cavity. Angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema was suspected, and anti-hypertensive medications were discontinued. Her symptoms improved within the next 24 hours, and repeat CT after 72 hours revealed marked improvement in stomach and small bowel thickening and resolution of ascites. The recognition of angiotensin-converting enzyme (ACE) and angiotensin receptor blocker (ARB) intestinal angioedema constitutes a challenge to primary care physicians, internists, emergency room personal and surgeons."],"offsets":[[119,1398]]}],"entities":[{"id":"7037","type":"Disease","text":["angioedema"],"offsets":[[57,67]],"normalized":[{"db_name":"MESH","db_id":"D000799"}]},{"id":"7038","type":"Disease","text":["hypertension"],"offsets":[[203,215]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"7039","type":"Chemical","text":["amlodipine"],"offsets":[[258,268]],"normalized":[{"db_name":"MESH","db_id":"D017311"}]},{"id":"7040","type":"Chemical","text":["benazapril"],"offsets":[[269,279]],"normalized":[{"db_name":"MESH","db_id":"C044946"}]},{"id":"7041","type":"Disease","text":["abdominal pain"],"offsets":[[354,368]],"normalized":[{"db_name":"MESH","db_id":"D015746"}]},{"id":"7042","type":"Disease","text":["nausea"],"offsets":[[370,376]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"7043","type":"Disease","text":["vomiting"],"offsets":[[381,389]],"normalized":[{"db_name":"MESH","db_id":"D014839"}]},{"id":"7044","type":"Disease","text":["angioedema"],"offsets":[[932,942]],"normalized":[{"db_name":"MESH","db_id":"D000799"}]},{"id":"7045","type":"Disease","text":["hypertensive"],"offsets":[[967,979]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"7046","type":"Disease","text":["ascites"],"offsets":[[1172,1179]],"normalized":[{"db_name":"MESH","db_id":"D001201"}]},{"id":"7047","type":"Chemical","text":["angiotensin"],"offsets":[[1200,1211]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"7048","type":"Chemical","text":["angiotensin"],"offsets":[[1240,1251]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"7049","type":"Disease","text":["intestinal angioedema"],"offsets":[[1275,1296]],"normalized":[{"db_name":"MESH","db_id":"D007410"},{"db_name":"MESH","db_id":"D000799"}]},{"id":"7050","type":"Disease","text":["intestinal"],"offsets":[[1275,1285]],"normalized":[{"db_name":"MESH","db_id":"D007410"}]},{"id":"7051","type":"Disease","text":["angioedema"],"offsets":[[1286,1296]],"normalized":[{"db_name":"MESH","db_id":"D000799"}]}],"events":[],"coreferences":[],"relations":[{"id":"7052","type":"CID","arg1_id":"7040","arg2_id":"7037","normalized":[]},{"id":"7053","type":"CID","arg1_id":"7040","arg2_id":"7044","normalized":[]},{"id":"7054","type":"CID","arg1_id":"7040","arg2_id":"7049","normalized":[]},{"id":"7055","type":"CID","arg1_id":"7040","arg2_id":"7051","normalized":[]},{"id":"7056","type":"CID","arg1_id":"7039","arg2_id":"7037","normalized":[]},{"id":"7057","type":"CID","arg1_id":"7039","arg2_id":"7044","normalized":[]},{"id":"7058","type":"CID","arg1_id":"7039","arg2_id":"7049","normalized":[]},{"id":"7059","type":"CID","arg1_id":"7039","arg2_id":"7051","normalized":[]},{"id":"7060","type":"CID","arg1_id":"7040","arg2_id":"7049","normalized":[]},{"id":"7061","type":"CID","arg1_id":"7040","arg2_id":"7050","normalized":[]},{"id":"7062","type":"CID","arg1_id":"7039","arg2_id":"7049","normalized":[]},{"id":"7063","type":"CID","arg1_id":"7039","arg2_id":"7050","normalized":[]}]}
{"id":"7064","document_id":"15858223","passages":[{"id":"7065","type":"title","text":["Valproic acid I: time course of lipid peroxidation biomarkers, liver toxicity, and valproic acid metabolite levels in rats."],"offsets":[[0,123]]},{"id":"7066","type":"abstract","text":["A single dose of valproic acid (VPA), which is a widely used antiepileptic drug, is associated with oxidative stress in rats, as recently demonstrated by elevated levels of 15-F(2t)-isoprostane (15-F(2t)-IsoP). To determine whether there was a temporal relationship between VPA-associated oxidative stress and hepatotoxicity, adult male Sprague-Dawley rats were treated ip with VPA (500 mg\/kg) or 0.9% saline (vehicle) once daily for 2, 4, 7, 10, or 14 days. Oxidative stress was assessed by determining plasma and liver levels of 15-F(2t)-IsoP, lipid hydroperoxides (LPO), and thiobarbituric acid reactive substances (TBARs). Plasma and liver 15-F(2t)-IsoP were elevated and reached a plateau after day 2 of VPA treatment compared to control. Liver LPO levels were not elevated until day 7 of treatment (1.8-fold versus control, p < 0.05). Liver and plasma TBARs were not increased until 14 days (2-fold vs. control, p < 0.05). Liver toxicity was evaluated based on serum levels of alpha-glutathione S-transferase (alpha-GST) and by histology. Serum alpha-GST levels were significantly elevated by day 4, which corresponded to hepatotoxicity as shown by the increasing incidence of inflammation of the liver capsule, necrosis, and steatosis throughout the study. The liver levels of beta-oxidation metabolites of VPA were decreased by day 14, while the levels of 4-ene-VPA and (E)-2,4-diene-VPA were not elevated throughout the study. Overall, these findings indicate that VPA treatment results in oxidative stress, as measured by levels of 15-F(2t)-IsoP, which precedes the onset of necrosis, steatosis, and elevated levels of serum alpha-GST."],"offsets":[[124,1769]]}],"entities":[{"id":"7067","type":"Chemical","text":["Valproic acid"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"7068","type":"Disease","text":["liver toxicity"],"offsets":[[63,77]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"7069","type":"Chemical","text":["valproic acid"],"offsets":[[83,96]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"7070","type":"Chemical","text":["valproic 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In our case, use of the Naranjo probability scale indicated a possible relationship between the hypertensive crisis and amisulpride and tiapride therapy. CONCLUSIONS: As of March 24, 2005, this is the first reported case of amisulpride- and tiapride-induced hypertensive crisis in a patient with pheochromocytoma. Physicians and other healthcare professionals should be aware of this potential adverse effect of tiapride and 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{"id":"7303","document_id":"15764424","passages":[{"id":"7304","type":"title","text":["Quantitative drug levels in stimulant psychosis: relationship to symptom severity, catecholamines and hyperkinesia."],"offsets":[[0,115]]},{"id":"7305","type":"abstract","text":["To examine the relationship between quantitative stimulant drug levels, catecholamines, and psychotic symptoms, nineteen patients in a psychiatric emergency service with a diagnosis of amphetamine- or cocaine-induced psychosis were interviewed, and plasma and urine were collected for quantitative assays of stimulant drug and catecholamine metabolite levels. Methamphetamine or amphetamine levels were related to several psychopathology scores and the global hyperkinesia rating. HVA levels were related to global hyperkinesia but not to psychopathology ratings. Although many other factors such as sensitization may play a role, intensity of stimulant-induced psychotic symptoms and stereotypies appears to be at least in part dose-related."],"offsets":[[116,858]]}],"entities":[{"id":"7306","type":"Disease","text":["psychosis"],"offsets":[[38,47]],"normalized":[{"db_name":"MESH","db_id":"D011605"}]},{"id":"7307","type":"Chemical","text":["catecholamines"],"offsets":[[83,97]],"normalized":[{"db_name":"MESH","db_id":"D002395"}]},{"id":"7308","type":"Disease","text":["hyperkinesia"],"offsets":[[102,114]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"7309","type":"Chemical","text":["catecholamines"],"offsets":[[188,202]],"normalized":[{"db_name":"MESH","db_id":"D002395"}]},{"id":"7310","type":"Disease","text":["psychotic symptoms"],"offsets":[[208,226]],"normalized":[{"db_name":"MESH","db_id":"D011605"}]},{"id":"7311","type":"Disease","text":["psychiatric"],"offsets":[[251,262]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"7312","type":"Chemical","text":["amphetamine"],"offsets":[[301,312]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"7313","type":"Chemical","text":["cocaine"],"offsets":[[317,324]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"7314","type":"Disease","text":["psychosis"],"offsets":[[333,342]],"normalized":[{"db_name":"MESH","db_id":"D011605"}]},{"id":"7315","type":"Chemical","text":["catecholamine"],"offsets":[[443,456]],"normalized":[{"db_name":"MESH","db_id":"D002395"}]},{"id":"7316","type":"Chemical","text":["Methamphetamine"],"offsets":[[476,491]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"7317","type":"Chemical","text":["amphetamine"],"offsets":[[495,506]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"7318","type":"Disease","text":["hyperkinesia"],"offsets":[[576,588]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"7319","type":"Disease","text":["hyperkinesia"],"offsets":[[631,643]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"7320","type":"Disease","text":["psychotic symptoms"],"offsets":[[778,796]],"normalized":[{"db_name":"MESH","db_id":"D011605"}]},{"id":"7321","type":"Disease","text":["stereotypies"],"offsets":[[801,813]],"normalized":[{"db_name":"MESH","db_id":"D019956"}]}],"events":[],"coreferences":[],"relations":[{"id":"7322","type":"CID","arg1_id":"7312","arg2_id":"7308","normalized":[]},{"id":"7323","type":"CID","arg1_id":"7312","arg2_id":"7318","normalized":[]},{"id":"7324","type":"CID","arg1_id":"7312","arg2_id":"7319","normalized":[]},{"id":"7325","type":"CID","arg1_id":"7317","arg2_id":"7308","normalized":[]},{"id":"7326","type":"CID","arg1_id":"7317","arg2_id":"7318","normalized":[]},{"id":"7327","type":"CID","arg1_id":"7317","arg2_id":"7319","normalized":[]},{"id":"7328","type":"CID","arg1_id":"7313","arg2_id":"7308","normalized":[]},{"id":"7329","type":"CID","arg1_id":"7313","arg2_id":"7318","normalized":[]},{"id":"7330","type":"CID","arg1_id":"7313","arg2_id":"7319","normalized":[]},{"id":"7331","type":"CID","arg1_id":"7316","arg2_id":"7306","normalized":[]},{"id":"7332","type":"CID","arg1_id":"7316","arg2_id":"7310","normalized":[]},{"id":"7333","type":"CID","arg1_id":"7316","arg2_id":"7314","normalized":[]},{"id":"7334","type":"CID","arg1_id":"7316","arg2_id":"7320","normalized":[]},{"id":"7335","type":"CID","arg1_id":"7313","arg2_id":"7306","normalized":[]},{"id":"7336","type":"CID","arg1_id":"7313","arg2_id":"7310","normalized":[]},{"id":"7337","type":"CID","arg1_id":"7313","arg2_id":"7314","normalized":[]},{"id":"7338","type":"CID","arg1_id":"7313","arg2_id":"7320","normalized":[]},{"id":"7339","type":"CID","arg1_id":"7316","arg2_id":"7308","normalized":[]},{"id":"7340","type":"CID","arg1_id":"7316","arg2_id":"7318","normalized":[]},{"id":"7341","type":"CID","arg1_id":"7316","arg2_id":"7319","normalized":[]},{"id":"7342","type":"CID","arg1_id":"7312","arg2_id":"7306","normalized":[]},{"id":"7343","type":"CID","arg1_id":"7312","arg2_id":"7310","normalized":[]},{"id":"7344","type":"CID","arg1_id":"7312","arg2_id":"7314","normalized":[]},{"id":"7345","type":"CID","arg1_id":"7312","arg2_id":"7320","normalized":[]},{"id":"7346","type":"CID","arg1_id":"7317","arg2_id":"7306","normalized":[]},{"id":"7347","type":"CID","arg1_id":"7317","arg2_id":"7310","normalized":[]},{"id":"7348","type":"CID","arg1_id":"7317","arg2_id":"7314","normalized":[]},{"id":"7349","type":"CID","arg1_id":"7317","arg2_id":"7320","normalized":[]}]}
{"id":"7350","document_id":"12101159","passages":[{"id":"7351","type":"title","text":["Delayed asystolic cardiac arrest after diltiazem overdose; resuscitation with high dose intravenous calcium."],"offsets":[[0,108]]},{"id":"7352","type":"abstract","text":["A 51 year old man took a mixed overdose including 1.8-3.6 g of diltiazem, paracetamol, aspirin, isosorbide nitrate, and alcohol. He initially presented to hospital after six hours with mild hypotension and was treated with activated charcoal and intravenous fluids. Eighteen hours after the overdose he had two generalised tonic-clonic seizures. The patient remained unresponsive with junctional bradycardia, unrecordable blood pressure, and then became asystolic. He was resuscitated with high dose (13.5 g) intravenous calcium and adrenaline (epinephrine). He required inotropic support and temporary pacing over the next 48 hours. This case suggests there is a role for aggressive high dose intravenous calcium therapy in severe diltiazem overdose, particularly with the onset of asystole. It should be considered early in cases of cardiac arrest after diltiazem overdose. The case also highlights the problems with delayed toxicity when whole bowel irrigation is not administered."],"offsets":[[109,1093]]}],"entities":[{"id":"7353","type":"Disease","text":["asystolic"],"offsets":[[8,17]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"7354","type":"Disease","text":["cardiac 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{"id":"7429","document_id":"6699841","passages":[{"id":"7430","type":"title","text":["Renal papillary necrosis due to naproxen."],"offsets":[[0,41]]},{"id":"7431","type":"abstract","text":["A 31-year-old man with rheumatoid arthritis, who had previously been treated with sulindac, fenoprofen calcium, high dose salicylates and gold salts, developed renal papillary necrosis (RPN) 4 months after institution of naproxen therapy. No other factor predisposing to RPN could be discovered. Sulindac was substituted for naproxen and no further adverse renal effects occurred over the next 12 months. We review previous reports linking RPN to antiinflammatory drug use and discuss possible advantages of sulindac in patients who have experienced renal toxicity from other antiinflammatory agents."],"offsets":[[42,642]]}],"entities":[{"id":"7432","type":"Disease","text":["Renal papillary necrosis"],"offsets":[[0,24]],"normalized":[{"db_name":"MESH","db_id":"D007681"}]},{"id":"7433","type":"Chemical","text":["naproxen"],"offsets":[[32,40]],"normalized":[{"db_name":"MESH","db_id":"D009288"}]},{"id":"7434","type":"Disease","text":["rheumatoid arthritis"],"offsets":[[65,85]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"7435","type":"Chemical","text":["sulindac"],"offsets":[[124,132]],"normalized":[{"db_name":"MESH","db_id":"D013467"}]},{"id":"7436","type":"Chemical","text":["fenoprofen calcium"],"offsets":[[134,152]],"normalized":[{"db_name":"MESH","db_id":"D005279"}]},{"id":"7437","type":"Chemical","text":["salicylates"],"offsets":[[164,175]],"normalized":[{"db_name":"MESH","db_id":"D012459"}]},{"id":"7438","type":"Chemical","text":["gold"],"offsets":[[180,184]],"normalized":[{"db_name":"MESH","db_id":"D006046"}]},{"id":"7439","type":"Disease","text":["renal papillary necrosis"],"offsets":[[202,226]],"normalized":[{"db_name":"MESH","db_id":"D007681"}]},{"id":"7440","type":"Disease","text":["RPN"],"offsets":[[228,231]],"normalized":[{"db_name":"MESH","db_id":"D007681"}]},{"id":"7441","type":"Chemical","text":["naproxen"],"offsets":[[263,271]],"normalized":[{"db_name":"MESH","db_id":"D009288"}]},{"id":"7442","type":"Disease","text":["RPN"],"offsets":[[313,316]],"normalized":[{"db_name":"MESH","db_id":"D007681"}]},{"id":"7443","type":"Chemical","text":["Sulindac"],"offsets":[[338,346]],"normalized":[{"db_name":"MESH","db_id":"D013467"}]},{"id":"7444","type":"Chemical","text":["naproxen"],"offsets":[[367,375]],"normalized":[{"db_name":"MESH","db_id":"D009288"}]},{"id":"7445","type":"Disease","text":["RPN"],"offsets":[[482,485]],"normalized":[{"db_name":"MESH","db_id":"D007681"}]},{"id":"7446","type":"Chemical","text":["sulindac"],"offsets":[[550,558]],"normalized":[{"db_name":"MESH","db_id":"D013467"}]},{"id":"7447","type":"Disease","text":["renal toxicity"],"offsets":[[592,606]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"7448","type":"CID","arg1_id":"7433","arg2_id":"7432","normalized":[]},{"id":"7449","type":"CID","arg1_id":"7433","arg2_id":"7439","normalized":[]},{"id":"7450","type":"CID","arg1_id":"7433","arg2_id":"7440","normalized":[]},{"id":"7451","type":"CID","arg1_id":"7433","arg2_id":"7442","normalized":[]},{"id":"7452","type":"CID","arg1_id":"7433","arg2_id":"7445","normalized":[]},{"id":"7453","type":"CID","arg1_id":"7441","arg2_id":"7432","normalized":[]},{"id":"7454","type":"CID","arg1_id":"7441","arg2_id":"7439","normalized":[]},{"id":"7455","type":"CID","arg1_id":"7441","arg2_id":"7440","normalized":[]},{"id":"7456","type":"CID","arg1_id":"7441","arg2_id":"7442","normalized":[]},{"id":"7457","type":"CID","arg1_id":"7441","arg2_id":"7445","normalized":[]},{"id":"7458","type":"CID","arg1_id":"7444","arg2_id":"7432","normalized":[]},{"id":"7459","type":"CID","arg1_id":"7444","arg2_id":"7439","normalized":[]},{"id":"7460","type":"CID","arg1_id":"7444","arg2_id":"7440","normalized":[]},{"id":"7461","type":"CID","arg1_id":"7444","arg2_id":"7442","normalized":[]},{"id":"7462","type":"CID","arg1_id":"7444","arg2_id":"7445","normalized":[]}]}
{"id":"7463","document_id":"6127992","passages":[{"id":"7464","type":"title","text":["Adverse interaction between beta-adrenergic blocking drugs and verapamil--report of three cases."],"offsets":[[0,96]]},{"id":"7465","type":"abstract","text":["Three patients with ischaemic heart disease developed profound cardiac failure, hypotension and bradycardia during combined therapy with verapamil and beta-adrenergic blocking drugs. This clinical picture resolved completely with cessation of the combined therapy. Baseline left ventricular function, assessed by cardiac catheterisation or nuclear angiography, was normal in two patients and only mildly reduced in the other. Simultaneously administration of beta-adrenergic blocking drugs and verapamil may result in profound adverse interactions and should only be administered with great caution."],"offsets":[[97,696]]}],"entities":[{"id":"7466","type":"Chemical","text":["beta-adrenergic blocking drugs"],"offsets":[[28,58]],"normalized":[{"db_name":"MESH","db_id":"D000319"}]},{"id":"7467","type":"Chemical","text":["verapamil"],"offsets":[[63,72]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"7468","type":"Disease","text":["ischaemic heart disease"],"offsets":[[117,140]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"7469","type":"Disease","text":["cardiac failure"],"offsets":[[160,175]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"7470","type":"Disease","text":["hypotension"],"offsets":[[177,188]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"7471","type":"Disease","text":["bradycardia"],"offsets":[[193,204]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"7472","type":"Chemical","text":["verapamil"],"offsets":[[234,243]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"7473","type":"Chemical","text":["beta-adrenergic blocking drugs"],"offsets":[[248,278]],"normalized":[{"db_name":"MESH","db_id":"D000319"}]},{"id":"7474","type":"Chemical","text":["beta-adrenergic blocking drugs"],"offsets":[[556,586]],"normalized":[{"db_name":"MESH","db_id":"D000319"}]},{"id":"7475","type":"Chemical","text":["verapamil"],"offsets":[[591,600]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]}],"events":[],"coreferences":[],"relations":[{"id":"7476","type":"CID","arg1_id":"7467","arg2_id":"7470","normalized":[]},{"id":"7477","type":"CID","arg1_id":"7472","arg2_id":"7470","normalized":[]},{"id":"7478","type":"CID","arg1_id":"7475","arg2_id":"7470","normalized":[]},{"id":"7479","type":"CID","arg1_id":"7466","arg2_id":"7469","normalized":[]},{"id":"7480","type":"CID","arg1_id":"7473","arg2_id":"7469","normalized":[]},{"id":"7481","type":"CID","arg1_id":"7474","arg2_id":"7469","normalized":[]},{"id":"7482","type":"CID","arg1_id":"7467","arg2_id":"7471","normalized":[]},{"id":"7483","type":"CID","arg1_id":"7472","arg2_id":"7471","normalized":[]},{"id":"7484","type":"CID","arg1_id":"7475","arg2_id":"7471","normalized":[]},{"id":"7485","type":"CID","arg1_id":"7467","arg2_id":"7469","normalized":[]},{"id":"7486","type":"CID","arg1_id":"7472","arg2_id":"7469","normalized":[]},{"id":"7487","type":"CID","arg1_id":"7475","arg2_id":"7469","normalized":[]},{"id":"7488","type":"CID","arg1_id":"7466","arg2_id":"7470","normalized":[]},{"id":"7489","type":"CID","arg1_id":"7473","arg2_id":"7470","normalized":[]},{"id":"7490","type":"CID","arg1_id":"7474","arg2_id":"7470","normalized":[]},{"id":"7491","type":"CID","arg1_id":"7466","arg2_id":"7471","normalized":[]},{"id":"7492","type":"CID","arg1_id":"7473","arg2_id":"7471","normalized":[]},{"id":"7493","type":"CID","arg1_id":"7474","arg2_id":"7471","normalized":[]}]}
{"id":"7494","document_id":"6115999","passages":[{"id":"7495","type":"title","text":["Adverse reactions to bendrofluazide and propranolol for the treatment of mild hypertension. Report of Medical Research Council Working Party on Mild to Moderate Hypertension."],"offsets":[[0,174]]},{"id":"7496","type":"abstract","text":["Participants in the Medical Research Council treatment trial for mild hypertension are randomly allocated to one of four treatment groups: bendrofluazide, propranolol, or a placebo for either of these drugs. The trial is single-blind. 23 582 patient-years of observation have been completed so far, 10 684 on active drugs and 12 898 on placebos. The results show an association between bendrofluazide treatment and impotence, and impotence also occurred more frequently in patients taking propranolol than in those taking placebos. Other adverse reactions significantly linked with active drugs include impaired glucose tolerance in men and women and gout in men, associated with bendrofluazide treatment, and Raynaud's phenomenon and dyspnoea in men and women taking propranolol. No corneal disease is known to have occurred in the propranolol group. Mean serum potassium level fell, and urea and uric acid levels rose, in men and women taking bendrofluazide. In the propranolol group, serum potassium and uric acid levels rose in both sexes, but the urea level rose significantly in women only."],"offsets":[[175,1271]]}],"entities":[{"id":"7497","type":"Chemical","text":["bendrofluazide"],"offsets":[[21,35]],"normalized":[{"db_name":"MESH","db_id":"D001539"}]},{"id":"7498","type":"Chemical","text":["propranolol"],"offsets":[[40,51]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"7499","type":"Disease","text":["hypertension"],"offsets":[[78,90]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"7500","type":"Disease","text":["Hypertension"],"offsets":[[161,173]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"7501","type":"Disease","text":["hypertension"],"offsets":[[245,257]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"7502","type":"Chemical","text":["bendrofluazide"],"offsets":[[314,328]],"normalized":[{"db_name":"MESH","db_id":"D001539"}]},{"id":"7503","type":"Chemical","text":["propranolol"],"offsets":[[330,341]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"7504","type":"Chemical","text":["bendrofluazide"],"offsets":[[561,575]],"normalized":[{"db_name":"MESH","db_id":"D001539"}]},{"id":"7505","type":"Disease","text":["impotence"],"offsets":[[590,599]],"normalized":[{"db_name":"MESH","db_id":"D007172"}]},{"id":"7506","type":"Disease","text":["impotence"],"offsets":[[605,614]],"normalized":[{"db_name":"MESH","db_id":"D007172"}]},{"id":"7507","type":"Chemical","text":["propranolol"],"offsets":[[664,675]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"7508","type":"Disease","text":["impaired 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disease"],"offsets":[[959,974]],"normalized":[{"db_name":"MESH","db_id":"D003316"}]},{"id":"7515","type":"Chemical","text":["propranolol"],"offsets":[[1008,1019]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"7516","type":"Chemical","text":["potassium"],"offsets":[[1038,1047]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"7517","type":"Chemical","text":["urea"],"offsets":[[1064,1068]],"normalized":[{"db_name":"MESH","db_id":"D014508"}]},{"id":"7518","type":"Chemical","text":["uric 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{"id":"7568","document_id":"18086064","passages":[{"id":"7569","type":"title","text":["Dexmedetomidine and cardiac protection for non-cardiac surgery: a meta-analysis of randomised controlled trials."],"offsets":[[0,112]]},{"id":"7570","type":"abstract","text":["We conducted a systematic review of the effects of dexmedetomidine on cardiac outcomes following non-cardiac surgery. We included prospective, randomised peri-operative studies of dexmedetomidine that reported mortality, cardiac morbidity or adverse drug events. A PubMed Central and EMBASE search was conducted up to July 2007. The reference lists of identified papers were examined for further trials. Of 425 studies identified, 20 were included in the meta-analysis (840 patients). Dexmedetomidine was associated with a trend towards improved cardiac outcomes; all-cause mortality (OR 0.27, 95% CI 0.01-7.13, p = 0.44), non-fatal myocardial infarction (OR 0.26, 95% CI 0.04-1.60, p = 0.14), and myocardial ischaemia (OR 0.65, 95% CI 0.26-1.63, p = 0.36). Peri-operative hypotension (26%, OR 3.80, 95% CI 1.91-7.54, p = 0.0001) and bradycardia (17%, OR 5.45, 95% CI 2.98-9.95, p < 0.00001) were significantly increased. An anticholinergic did not reduce the incidence of bradycardia (p = 0.43). A randomised placebo-controlled trial of dexmedetomidine is warranted."],"offsets":[[113,1180]]}],"entities":[{"id":"7571","type":"Chemical","text":["Dexmedetomidine"],"offsets":[[0,15]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"7572","type":"Chemical","text":["dexmedetomidine"],"offsets":[[164,179]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"7573","type":"Chemical","text":["dexmedetomidine"],"offsets":[[293,308]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"7574","type":"Chemical","text":["Dexmedetomidine"],"offsets":[[598,613]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"7575","type":"Disease","text":["myocardial infarction"],"offsets":[[746,767]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"7576","type":"Disease","text":["myocardial ischaemia"],"offsets":[[811,831]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"7577","type":"Disease","text":["hypotension"],"offsets":[[886,897]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"7578","type":"Disease","text":["bradycardia"],"offsets":[[947,958]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"7579","type":"Disease","text":["bradycardia"],"offsets":[[1086,1097]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"7580","type":"Chemical","text":["dexmedetomidine"],"offsets":[[1151,1166]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]}],"events":[],"coreferences":[],"relations":[{"id":"7581","type":"CID","arg1_id":"7571","arg2_id":"7578","normalized":[]},{"id":"7582","type":"CID","arg1_id":"7571","arg2_id":"7579","normalized":[]},{"id":"7583","type":"CID","arg1_id":"7572","arg2_id":"7578","normalized":[]},{"id":"7584","type":"CID","arg1_id":"7572","arg2_id":"7579","normalized":[]},{"id":"7585","type":"CID","arg1_id":"7573","arg2_id":"7578","normalized":[]},{"id":"7586","type":"CID","arg1_id":"7573","arg2_id":"7579","normalized":[]},{"id":"7587","type":"CID","arg1_id":"7574","arg2_id":"7578","normalized":[]},{"id":"7588","type":"CID","arg1_id":"7574","arg2_id":"7579","normalized":[]},{"id":"7589","type":"CID","arg1_id":"7580","arg2_id":"7578","normalized":[]},{"id":"7590","type":"CID","arg1_id":"7580","arg2_id":"7579","normalized":[]},{"id":"7591","type":"CID","arg1_id":"7571","arg2_id":"7577","normalized":[]},{"id":"7592","type":"CID","arg1_id":"7572","arg2_id":"7577","normalized":[]},{"id":"7593","type":"CID","arg1_id":"7573","arg2_id":"7577","normalized":[]},{"id":"7594","type":"CID","arg1_id":"7574","arg2_id":"7577","normalized":[]},{"id":"7595","type":"CID","arg1_id":"7580","arg2_id":"7577","normalized":[]}]}
{"id":"7596","document_id":"12739036","passages":[{"id":"7597","type":"title","text":["Differential diagnosis of high serum creatine kinase levels in systemic lupus erythematosus."],"offsets":[[0,92]]},{"id":"7598","type":"abstract","text":["We report the clinical and bioptic findings for a 57-year-old woman with severe chloroquine-induced myopathy. Since 1989, she had been suffering from systemic lupus erythematosus (SLE) with renal involvement and undergone periods of treatment with azathioprine and cyclophosphamide. Additional therapy with chloroquine (CQ) was started because of arthralgia. At the same time, slightly increased creatine kinase (CK) levels were noted. Myositis was suspected, and the patient was treated with steroids. The CK increase persisted, however, and she developed progressive muscular weakness and muscular atrophy. Routine controls revealed markedly elevated CK levels of 1,700 U\/l. The neurological and electrophysiological findings were not typical of myositis. Thus, muscle biopsy of the deltoid muscle was performed in order to exclude polymyositis or toxic myopathy. As it revealed chloroquine-induced myopathy, medication was stopped. Discriminating between primary SLE-induced affection of the musculoskeletal system and drug-induced side effects is important for appropriate treatment of SLE patients."],"offsets":[[93,1196]]}],"entities":[{"id":"7599","type":"Chemical","text":["creatine"],"offsets":[[37,45]],"normalized":[{"db_name":"MESH","db_id":"D003401"}]},{"id":"7600","type":"Disease","text":["systemic lupus erythematosus"],"offsets":[[63,91]],"normalized":[{"db_name":"MESH","db_id":"D008180"}]},{"id":"7601","type":"Chemical","text":["chloroquine"],"offsets":[[173,184]],"normalized":[{"db_name":"MESH","db_id":"D002738"}]},{"id":"7602","type":"Disease","text":["myopathy"],"offsets":[[193,201]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"7603","type":"Disease","text":["systemic lupus erythematosus"],"offsets":[[243,271]],"normalized":[{"db_name":"MESH","db_id":"D008180"}]},{"id":"7604","type":"Disease","text":["SLE"],"offsets":[[273,276]],"normalized":[{"db_name":"MESH","db_id":"D008180"}]},{"id":"7605","type":"Disease","text":["renal involvement"],"offsets":[[283,300]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7606","type":"Chemical","text":["azathioprine"],"offsets":[[341,353]],"normalized":[{"db_name":"MESH","db_id":"D001379"}]},{"id":"7607","type":"Chemical","text":["cyclophosphamide"],"offsets":[[358,374]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"7608","type":"Chemical","text":["chloroquine"],"offsets":[[400,411]],"normalized":[{"db_name":"MESH","db_id":"D002738"}]},{"id":"7609","type":"Chemical","text":["CQ"],"offsets":[[413,415]],"normalized":[{"db_name":"MESH","db_id":"D002738"}]},{"id":"7610","type":"Disease","text":["arthralgia"],"offsets":[[440,450]],"normalized":[{"db_name":"MESH","db_id":"D018771"}]},{"id":"7611","type":"Chemical","text":["creatine"],"offsets":[[489,497]],"normalized":[{"db_name":"MESH","db_id":"D003401"}]},{"id":"7612","type":"Disease","text":["Myositis"],"offsets":[[529,537]],"normalized":[{"db_name":"MESH","db_id":"D009220"}]},{"id":"7613","type":"Chemical","text":["steroids"],"offsets":[[586,594]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"7614","type":"Disease","text":["muscular weakness"],"offsets":[[662,679]],"normalized":[{"db_name":"MESH","db_id":"D018908"}]},{"id":"7615","type":"Disease","text":["muscular atrophy"],"offsets":[[684,700]],"normalized":[{"db_name":"MESH","db_id":"D009133"}]},{"id":"7616","type":"Disease","text":["myositis"],"offsets":[[841,849]],"normalized":[{"db_name":"MESH","db_id":"D009220"}]},{"id":"7617","type":"Disease","text":["polymyositis"],"offsets":[[927,939]],"normalized":[{"db_name":"MESH","db_id":"D017285"}]},{"id":"7618","type":"Disease","text":["myopathy"],"offsets":[[949,957]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"7619","type":"Chemical","text":["chloroquine"],"offsets":[[974,985]],"normalized":[{"db_name":"MESH","db_id":"D002738"}]},{"id":"7620","type":"Disease","text":["myopathy"],"offsets":[[994,1002]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"7621","type":"Disease","text":["SLE"],"offsets":[[1059,1062]],"normalized":[{"db_name":"MESH","db_id":"D008180"}]},{"id":"7622","type":"Disease","text":["affection of the musculoskeletal system"],"offsets":[[1071,1110]],"normalized":[{"db_name":"MESH","db_id":"D009140"}]},{"id":"7623","type":"Disease","text":["SLE"],"offsets":[[1183,1186]],"normalized":[{"db_name":"MESH","db_id":"D008180"}]}],"events":[],"coreferences":[],"relations":[{"id":"7624","type":"CID","arg1_id":"7601","arg2_id":"7614","normalized":[]},{"id":"7625","type":"CID","arg1_id":"7608","arg2_id":"7614","normalized":[]},{"id":"7626","type":"CID","arg1_id":"7609","arg2_id":"7614","normalized":[]},{"id":"7627","type":"CID","arg1_id":"7619","arg2_id":"7614","normalized":[]},{"id":"7628","type":"CID","arg1_id":"7601","arg2_id":"7615","normalized":[]},{"id":"7629","type":"CID","arg1_id":"7608","arg2_id":"7615","normalized":[]},{"id":"7630","type":"CID","arg1_id":"7609","arg2_id":"7615","normalized":[]},{"id":"7631","type":"CID","arg1_id":"7619","arg2_id":"7615","normalized":[]}]}
{"id":"7632","document_id":"12093990","passages":[{"id":"7633","type":"title","text":["Intravenous ribavirin treatment for severe adenovirus disease in immunocompromised children."],"offsets":[[0,92]]},{"id":"7634","type":"abstract","text":["BACKGROUND: Adenovirus is an important cause of morbidity and mortality in the immunocompromised host. The incidence of severe adenovirus disease in pediatrics is increasing in association with growing numbers of immunocompromised children, where case fatality rates as high as 50% to 80% have been reported. There are no approved antiviral agents with proven efficacy for the treatment of severe adenovirus disease, nor are there any prospective randomized, controlled trials of potentially useful anti-adenovirus therapies. Apparent clinical success in the treatment of severe adenovirus disease is limited to a few case reports and small series. Experience is greatest with intravenous ribavirin and cidofovir. Ribavirin, a guanosine analogue, has broad antiviral activity against both RNA and DNA viruses, including documented activity against adenovirus in vitro. Ribavirin is licensed in aerosol form for the treatment of respiratory syncytial virus infection, and orally in combination with interferon to treat hepatitis C. Intravenous ribavirin is the treatment of choice for infection with hemorrhagic fever viruses. The most common adverse effect of intravenous ribavirin is reversible mild anemia. The use of cidofovir in severe adenovirus infection has been limited by adverse effects, the most significant of which is nephrotoxicity. OBJECTIVE: We report our experience with intravenous ribavirin therapy for severe adenovirus disease in a series of immunocompromised children and review the literature. DESIGN\/METHODS: We retrospectively reviewed the medical records of 5 children treated with intravenous ribavirin for documented severe adenovirus disease. Two patients developed adenovirus hemorrhagic cystitis after cardiac and bone marrow transplants, respectively. The bone marrow transplant patient also received intravenous cidofovir for progressive disseminated disease. An additional 3 children developed adenovirus pneumonia; 2 were neonates, 1 of whom had partial DiGeorge syndrome. The remaining infant had recently undergone a cardiac transplant. Intravenous ribavirin was administered on a compassionate-use protocol. RESULTS: Complete clinical recovery followed later by viral clearance was observed in 2 children: the cardiac transplant recipient with adenovirus hemorrhagic cystitis and the immunocompetent neonate with adenovirus pneumonia. The remaining 3 children died of adenovirus disease. Intravenous ribavirin therapy was well tolerated. Use of cidofovir in 1 child was associated with progressive renal failure and neutropenia. DISCUSSION: Our series of patients is representative of the spectrum of immunocompromised children at greatest risk for severe adenovirus disease, namely solid-organ and bone marrow transplant recipients, neonates, and children with immunodeficiency. Although intravenous ribavirin was not effective for all children with severe adenovirus disease in this series or in the literature, therapy is unlikely to be of benefit if begun late in the course of the infection. Early identification, eg by polymerase chain reaction of those patients at risk of disseminated adenovirus disease may permit earlier antiviral treatment and better evaluation of therapeutic response. CONCLUSIONS: Two of 5 children with severe adenovirus disease treated with intravenous ribavirin recovered. The availability of newer rapid diagnostic techniques, such as polymerase chain reaction, may make earlier, more effective treatment of adenovirus infection possible. Given the seriousness and increasing prevalence of adenovirus disease in certain hosts, especially children, a large, multicenter clinical trial of potentially useful anti-adenoviral therapies, such as intravenous ribavirin, is clearly required to demonstrate the most effective and least toxic therapy."],"offsets":[[93,3907]]}],"entities":[{"id":"7635","type":"Chemical","text":["ribavirin"],"offsets":[[12,21]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"7636","type":"Disease","text":["adenovirus disease"],"offsets":[[43,61]],"normalized":[{"db_name":"MESH","db_id":"D000257"}]},{"id":"7637","type":"Disease","text":["adenovirus disease"],"offsets":[[220,238]],"normalized":[{"db_name":"MESH","db_id":"D000257"}]},{"id":"7638","type":"Disease","text":["adenovirus disease"],"offsets":[[490,508]],"normalized":[{"db_name":"MESH","db_id":"D000257"}]},{"id":"7639","type":"Disease","text":["adenovirus disease"],"offsets":[[672,690]],"normalized":[{"db_name":"MESH","db_id":"D000257"}]},{"id":"7640","type":"Chemical","text":["ribavirin"],"offsets":[[782,791]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"7641","type":"Chemical","text":["cidofovir"],"offsets":[[796,805]],"normalized":[{"db_name":"MESH","db_id":"C059262"}]},{"id":"7642","type":"Chemical","text":["Ribavirin"],"offsets":[[807,816]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"7643","type":"Chemical","text":["guanosine"],"offsets":[[820,829]],"normalized":[{"db_name":"MESH","db_id":"D006151"}]},{"id":"7644","type":"Chemical","text":["Ribavirin"],"offsets":[[962,971]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"7645","type":"Disease","text":["respiratory syncytial virus infection"],"offsets":[[1021,1058]],"normalized":[{"db_name":"MESH","db_id":"D018357"}]},{"id":"7646","type":"Disease","text":["hepatitis C"],"offsets":[[1111,1122]],"normalized":[{"db_name":"MESH","db_id":"D006526"}]},{"id":"7647","type":"Chemical","text":["ribavirin"],"offsets":[[1136,1145]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"7648","type":"Disease","text":["infection with hemorrhagic fever viruses"],"offsets":[[1177,1217]],"normalized":[{"db_name":"MESH","db_id":"D006482"}]},{"id":"7649","type":"Chemical","text":["ribavirin"],"offsets":[[1265,1274]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"7650","type":"Disease","text":["anemia"],"offsets":[[1294,1300]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"7651","type":"Chemical","text":["cidofovir"],"offsets":[[1313,1322]],"normalized":[{"db_name":"MESH","db_id":"C059262"}]},{"id":"7652","type":"Disease","text":["adenovirus infection"],"offsets":[[1333,1353]],"normalized":[{"db_name":"MESH","db_id":"D000257"}]},{"id":"7653","type":"Disease","text":["nephrotoxicity"],"offsets":[[1424,1438]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7654","type":"Chemical","text":["ribavirin"],"offsets":[[1493,1502]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"7655","type":"Disease","text":["adenovirus disease"],"offsets":[[1522,1540]],"normalized":[{"db_name":"MESH","db_id":"D000257"}]},{"id":"7656","type":"Chemical","text":["ribavirin"],"offsets":[[1713,1722]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"7657","type":"Disease","text":["adenovirus disease"],"offsets":[[1745,1763]],"normalized":[{"db_name":"MESH","db_id":"D000257"}]},{"id":"7658","type":"Disease","text":["hemorrhagic cystitis"],"offsets":[[1799,1819]],"normalized":[{"db_name":"MESH","db_id":"D006470"},{"db_name":"MESH","db_id":"D003556"}]},{"id":"7659","type":"Disease","text":["hemorrhagic"],"offsets":[[1799,1810]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"7660","type":"Disease","text":["cystitis"],"offsets":[[1811,1819]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"7661","type":"Chemical","text":["cidofovir"],"offsets":[[1938,1947]],"normalized":[{"db_name":"MESH","db_id":"C059262"}]},{"id":"7662","type":"Disease","text":["adenovirus pneumonia"],"offsets":[[2021,2041]],"normalized":[{"db_name":"MESH","db_id":"D000257"},{"db_name":"MESH","db_id":"D011024"}]},{"id":"7663","type":"Disease","text":["adenovirus"],"offsets":[[2021,2031]],"normalized":[{"db_name":"MESH","db_id":"D000257"}]},{"id":"7664","type":"Disease","text":["pneumonia"],"offsets":[[2032,2041]],"normalized":[{"db_name":"MESH","db_id":"D011024"}]},{"id":"7665","type":"Disease","text":["DiGeorge syndrome"],"offsets":[[2082,2099]],"normalized":[{"db_name":"MESH","db_id":"D004062"}]},{"id":"7666","type":"Chemical","text":["ribavirin"],"offsets":[[2179,2188]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"7667","type":"Disease","text":["hemorrhagic cystitis"],"offsets":[[2386,2406]],"normalized":[{"db_name":"MESH","db_id":"D006470"},{"db_name":"MESH","db_id":"D003556"}]},{"id":"7668","type":"Disease","text":["hemorrhagic"],"offsets":[[2386,2397]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"7669","type":"Disease","text":["cystitis"],"offsets":[[2398,2406]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"7670","type":"Disease","text":["adenovirus 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{"id":"7697","document_id":"3962737","passages":[{"id":"7698","type":"title","text":["Hepatotoxicity of amiodarone."],"offsets":[[0,29]]},{"id":"7699","type":"abstract","text":["Amiodarone has proved very effective in the treatment of otherwise resistant cardiac tachyarrhythmias. The use of amiodarone has, however, been limited due to its serious side-effects. A patient with cholestatic hepatitis due to amiodarone treatment is presented below and a review of the hepatotoxicity of amiodarone is given. It is concluded that solid evidence exists of hepatic injury due to amiodarone treatment, including steatosis, alterations resembling alcoholic hepatitis, cholestatic hepatitis and micronodular cirrhosis of the liver. Patients receiving amiodarone should be regularly screened with respect to hepatic enzyme levels. Therapy should be discontinued on the suspicion of cholestatic injury or hepatomegaly."],"offsets":[[30,760]]}],"entities":[{"id":"7700","type":"Disease","text":["Hepatotoxicity"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"7701","type":"Chemical","text":["amiodarone"],"offsets":[[18,28]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"7702","type":"Chemical","text":["Amiodarone"],"offsets":[[30,40]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"7703","type":"Disease","text":["tachyarrhythmias"],"offsets":[[115,131]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]},{"id":"7704","type":"Chemical","text":["amiodarone"],"offsets":[[144,154]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"7705","type":"Disease","text":["cholestatic 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{"id":"7820","document_id":"2716967","passages":[{"id":"7821","type":"title","text":["Catalepsy induced by combinations of ketamine and morphine: potentiation, antagonism, tolerance and cross-tolerance in the rat."],"offsets":[[0,127]]},{"id":"7822","type":"abstract","text":["Previous studies demonstrated that both ketamine and morphine induced analgesia and catalepsy in the rat. Pre-treatment with ketamine produced cross-tolerance to morphine, whereas pretreatment with morphine did not induce cross-tolerance to ketamine but rather augmented the cataleptic response; this augmentation was attributed to residual morphine in the brain. The present studies explored the duration of the loss of righting reflex induced by sub-effective doses of ketamine and morphine, administered simultaneously. There was mutual potentiation between sub-effective doses of ketamine and morphine, but sub-effective doses of ketamine partly antagonized fully-effective doses of morphine. Latency to the loss of righting reflex, rigidity and behavior on recovery, reflected the relative predominance of ketamine or morphine in each combination. Naloxone inhibited the induced cataleptic effects. The degree and time course of development of tolerance to daily administration of sub-effective dose combinations of ketamine and morphine were similar. Rats, tolerant to ketamine-dominant combinations, were cross-tolerant to both drugs, while those tolerant to morphine-dominant combinations were cross-tolerant to morphine but showed either no cross-tolerance or an augmented response to ketamine. While the mutual potentiation, antagonism and tolerance suggest common mechanisms for the induced catalepsy, differences in latency, rigidity and behavior, asymmetry of cross-tolerance and a widely-different ID50 for naloxone would argue against an action at a single opioid 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{"id":"7971","document_id":"19642243","passages":[{"id":"7972","type":"title","text":["Acute renal failure in patients with AIDS on tenofovir while receiving prolonged vancomycin course for osteomyelitis."],"offsets":[[0,117]]},{"id":"7973","type":"abstract","text":["Renal failure developed after a prolonged course of vancomycin therapy in 2 patients who were receiving tenofovir disoproxil fumarate as part of an antiretroviral regimen. Tenofovir has been implicated in the development of Fanconi syndrome and renal insufficiency because of its effects on the proximal renal tubule. Vancomycin nephrotoxicity is infrequent but may result from coadministration with a nephrotoxic agent. Clinicians should be aware that tenofovir may raise the risk of renal failure during prolonged administration of vancomycin."],"offsets":[[118,663]]}],"entities":[{"id":"7974","type":"Disease","text":["Acute renal failure"],"offsets":[[0,19]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"7975","type":"Disease","text":["AIDS"],"offsets":[[37,41]],"normalized":[{"db_name":"MESH","db_id":"D000163"}]},{"id":"7976","type":"Chemical","text":["tenofovir"],"offsets":[[45,54]],"normalized":[{"db_name":"MESH","db_id":"C096918"}]},{"id":"7977","type":"Chemical","text":["vancomycin"],"offsets":[[81,91]],"normalized":[{"db_name":"MESH","db_id":"D014640"}]},{"id":"7978","type":"Disease","text":["osteomyelitis"],"offsets":[[103,116]],"normalized":[{"db_name":"MESH","db_id":"D010019"}]},{"id":"7979","type":"Disease","text":["Renal failure"],"offsets":[[118,131]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"7980","type":"Chemical","text":["vancomycin"],"offsets":[[170,180]],"normalized":[{"db_name":"MESH","db_id":"D014640"}]},{"id":"7981","type":"Chemical","text":["tenofovir disoproxil fumarate"],"offsets":[[222,251]],"normalized":[{"db_name":"MESH","db_id":"C418563"}]},{"id":"7982","type":"Chemical","text":["Tenofovir"],"offsets":[[290,299]],"normalized":[{"db_name":"MESH","db_id":"C096918"}]},{"id":"7983","type":"Disease","text":["Fanconi syndrome"],"offsets":[[342,358]],"normalized":[{"db_name":"MESH","db_id":"D005198"}]},{"id":"7984","type":"Disease","text":["renal insufficiency"],"offsets":[[363,382]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"7985","type":"Chemical","text":["Vancomycin"],"offsets":[[436,446]],"normalized":[{"db_name":"MESH","db_id":"D014640"}]},{"id":"7986","type":"Disease","text":["nephrotoxicity"],"offsets":[[447,461]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7987","type":"Disease","text":["nephrotoxic"],"offsets":[[520,531]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"7988","type":"Chemical","text":["tenofovir"],"offsets":[[571,580]],"normalized":[{"db_name":"MESH","db_id":"C096918"}]},{"id":"7989","type":"Disease","text":["renal failure"],"offsets":[[603,616]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"7990","type":"Chemical","text":["vancomycin"],"offsets":[[652,662]],"normalized":[{"db_name":"MESH","db_id":"D014640"}]}],"events":[],"coreferences":[],"relations":[{"id":"7991","type":"CID","arg1_id":"7977","arg2_id":"7974","normalized":[]},{"id":"7992","type":"CID","arg1_id":"7980","arg2_id":"7974","normalized":[]},{"id":"7993","type":"CID","arg1_id":"7985","arg2_id":"7974","normalized":[]},{"id":"7994","type":"CID","arg1_id":"7990","arg2_id":"7974","normalized":[]},{"id":"7995","type":"CID","arg1_id":"7981","arg2_id":"7974","normalized":[]}]}
{"id":"7996","document_id":"17682013","passages":[{"id":"7997","type":"title","text":["Delayed leukoencephalopathy with stroke-like presentation in chemotherapy recipients."],"offsets":[[0,85]]},{"id":"7998","type":"abstract","text":["BACKGROUND: A transient leukoencephalopathy mimicking cerebrovascular accident has been described as a complication of chemotherapy, most commonly in recipients of intrathecal methotrexate for childhood leukaemia. Recently published neuroimaging data suggest a common pathophysiology associated with a variety of chemotherapy agents and modes of administration. METHODS: We reviewed the medical literature for single reports and case series of patients presenting with stroke-like episodes while receiving systemic or intrathecal chemotherapy. We only included studies providing detailed neuroimaging data. Patients with cerebrovascular accidents were excluded. RESULTS: We identified 27 reports of toxic leukoencephalopathy in patients treated with methotrexate (intrathecal, systemic), 5-fluorouracil and its derivative carmofur, and capecitabine. Diffusion weighted imaging (DWI) of all patients revealed well demarcated hyperintense lesions within the subcortical white matter of the cerebral hemispheres and the corpus callosum, corresponding to areas of decreased proton diffusion on apparent diffusion coefficient (ADC) maps (available in 21\/27 patients). Lesions exceeded the confines of adjacent vascular territories. Complete resolution of symptoms within 1-4 days was accompanied by normalisation of ADC abnormalities. However, fluid attenuated inversion recovery (FLAIR) sequences frequently revealed persistent white matter abnormalities. CONCLUSIONS: Several pathophysiological models of delayed leukoencephalopathy after exposure to intrathecal or systemic chemotherapy have been proposed. DWI findings in this cohort are indicative of cytotoxic oedema within cerebral white matter and lend support to an at least partially reversible metabolic derangement as the basis for this syndrome."],"offsets":[[86,1889]]}],"entities":[{"id":"7999","type":"Disease","text":["leukoencephalopathy"],"offsets":[[8,27]],"normalized":[{"db_name":"MESH","db_id":"D056784"}]},{"id":"8000","type":"Disease","text":["stroke"],"offsets":[[33,39]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"8001","type":"Disease","text":["leukoencephalopathy"],"offsets":[[110,129]],"normalized":[{"db_name":"MESH","db_id":"D056784"}]},{"id":"8002","type":"Disease","text":["cerebrovascular accident"],"offsets":[[140,164]],"normalized":[{"db_name":"MESH","db_id":"D002544"}]},{"id":"8003","type":"Chemical","text":["methotrexate"],"offsets":[[262,274]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"8004","type":"Disease","text":["leukaemia"],"offsets":[[289,298]],"normalized":[{"db_name":"MESH","db_id":"D007938"}]},{"id":"8005","type":"Disease","text":["stroke"],"offsets":[[555,561]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"8006","type":"Disease","text":["cerebrovascular accidents"],"offsets":[[707,732]],"normalized":[{"db_name":"MESH","db_id":"D002544"}]},{"id":"8007","type":"Disease","text":["leukoencephalopathy"],"offsets":[[791,810]],"normalized":[{"db_name":"MESH","db_id":"D056784"}]},{"id":"8008","type":"Chemical","text":["methotrexate"],"offsets":[[836,848]],"normalized":[{"db_name":"MESH","db_id":"D008727"}]},{"id":"8009","type":"Chemical","text":["5-fluorouracil"],"offsets":[[874,888]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"8010","type":"Chemical","text":["carmofur"],"offsets":[[908,916]],"normalized":[{"db_name":"MESH","db_id":"C017367"}]},{"id":"8011","type":"Chemical","text":["capecitabine"],"offsets":[[922,934]],"normalized":[{"db_name":"MESH","db_id":"C110904"}]},{"id":"8012","type":"Disease","text":["lesions within the subcortical white matter"],"offsets":[[1023,1066]],"normalized":[{"db_name":"MESH","db_id":"D056784"}]},{"id":"8013","type":"Disease","text":["white matter abnormalities"],"offsets":[[1510,1536]],"normalized":[{"db_name":"MESH","db_id":"D056784"}]},{"id":"8014","type":"Disease","text":["leukoencephalopathy"],"offsets":[[1596,1615]],"normalized":[{"db_name":"MESH","db_id":"D056784"}]},{"id":"8015","type":"Disease","text":["cytotoxic oedema within cerebral white matter"],"offsets":[[1737,1782]],"normalized":[{"db_name":"MESH","db_id":"D001929"}]}],"events":[],"coreferences":[],"relations":[{"id":"8016","type":"CID","arg1_id":"8003","arg2_id":"7999","normalized":[]},{"id":"8017","type":"CID","arg1_id":"8003","arg2_id":"8001","normalized":[]},{"id":"8018","type":"CID","arg1_id":"8003","arg2_id":"8007","normalized":[]},{"id":"8019","type":"CID","arg1_id":"8003","arg2_id":"8012","normalized":[]},{"id":"8020","type":"CID","arg1_id":"8003","arg2_id":"8013","normalized":[]},{"id":"8021","type":"CID","arg1_id":"8003","arg2_id":"8014","normalized":[]},{"id":"8022","type":"CID","arg1_id":"8008","arg2_id":"7999","normalized":[]},{"id":"8023","type":"CID","arg1_id":"8008","arg2_id":"8001","normalized":[]},{"id":"8024","type":"CID","arg1_id":"8008","arg2_id":"8007","normalized":[]},{"id":"8025","type":"CID","arg1_id":"8008","arg2_id":"8012","normalized":[]},{"id":"8026","type":"CID","arg1_id":"8008","arg2_id":"8013","normalized":[]},{"id":"8027","type":"CID","arg1_id":"8008","arg2_id":"8014","normalized":[]},{"id":"8028","type":"CID","arg1_id":"8010","arg2_id":"7999","normalized":[]},{"id":"8029","type":"CID","arg1_id":"8010","arg2_id":"8001","normalized":[]},{"id":"8030","type":"CID","arg1_id":"8010","arg2_id":"8007","normalized":[]},{"id":"8031","type":"CID","arg1_id":"8010","arg2_id":"8012","normalized":[]},{"id":"8032","type":"CID","arg1_id":"8010","arg2_id":"8013","normalized":[]},{"id":"8033","type":"CID","arg1_id":"8010","arg2_id":"8014","normalized":[]},{"id":"8034","type":"CID","arg1_id":"8009","arg2_id":"7999","normalized":[]},{"id":"8035","type":"CID","arg1_id":"8009","arg2_id":"8001","normalized":[]},{"id":"8036","type":"CID","arg1_id":"8009","arg2_id":"8007","normalized":[]},{"id":"8037","type":"CID","arg1_id":"8009","arg2_id":"8012","normalized":[]},{"id":"8038","type":"CID","arg1_id":"8009","arg2_id":"8013","normalized":[]},{"id":"8039","type":"CID","arg1_id":"8009","arg2_id":"8014","normalized":[]},{"id":"8040","type":"CID","arg1_id":"8011","arg2_id":"7999","normalized":[]},{"id":"8041","type":"CID","arg1_id":"8011","arg2_id":"8001","normalized":[]},{"id":"8042","type":"CID","arg1_id":"8011","arg2_id":"8007","normalized":[]},{"id":"8043","type":"CID","arg1_id":"8011","arg2_id":"8012","normalized":[]},{"id":"8044","type":"CID","arg1_id":"8011","arg2_id":"8013","normalized":[]},{"id":"8045","type":"CID","arg1_id":"8011","arg2_id":"8014","normalized":[]}]}
{"id":"8046","document_id":"16725121","passages":[{"id":"8047","type":"title","text":["Down-regulation of norepinephrine transporter function induced by chronic administration of desipramine linking to the alteration of sensitivity of local-anesthetics-induced convulsions and the counteraction by co-administration with local anesthetics."],"offsets":[[0,252]]},{"id":"8048","type":"abstract","text":["Alterations of norepinephrine transporter (NET) function by chronic inhibition of NET in relation to sensitization to seizures induce by cocaine and local anesthetics were studied in mice. Daily administration of desipramine, an inhibitor of the NET, for 5 days decreased [(3)H]norepinephrine uptake in the P2 fractions of hippocampus but not cortex, striatum or amygdalae. Co-administration of lidocaine, bupivacaine or tricaine with desipramine reversed this effect. Daily treatment of cocaine increased [(3)H]norepinephrine uptake into the hippocampus. Daily administration of desipramine increased the incidence of appearance of lidocaine-induced convulsions and decreased that of cocaine-induced convulsions. Co-administration of lidocaine with desipramine reversed the changes of convulsive activity of lidocaine and cocaine induced by repeated administration of desipramine. These results suggest that down-regulation of hippocampal NET induced by chronic administration of desipramine may be relevant to desipramine-induced sensitization of lidocaine convulsions. Inhibition of Na(+) channels by local anesthetics may regulate desipramine-induced down-regulation of NET function. Repeated administration of cocaine induces up-regulation of hippocampal NET function. Desipramine-induced sensitization of lidocaine seizures may have a mechanism distinct from kindling resulting from repeated administration of cocaine."],"offsets":[[253,1677]]}],"entities":[{"id":"8049","type":"Chemical","text":["norepinephrine"],"offsets":[[19,33]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"8050","type":"Chemical","text":["desipramine"],"offsets":[[92,103]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"8051","type":"Disease","text":["convulsions"],"offsets":[[174,185]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"8052","type":"Chemical","text":["norepinephrine"],"offsets":[[268,282]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"8053","type":"Disease","text":["seizures"],"offsets":[[371,379]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"8054","type":"Chemical","text":["cocaine"],"offsets":[[390,397]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"8055","type":"Chemical","text":["desipramine"],"offsets":[[466,477]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"8056","type":"Chemical","text":["norepinephrine"],"offsets":[[531,545]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"8057","type":"Chemical","text":["lidocaine"],"offsets":[[648,657]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"8058","type":"Chemical","text":["bupivacaine"],"offsets":[[659,670]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"8059","type":"Chemical","text":["tricaine"],"offsets":[[674,682]],"normalized":[{"db_name":"MESH","db_id":"C003636"}]},{"id":"8060","type":"Chemical","text":["desipramine"],"offsets":[[688,699]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"8061","type":"Chemical","text":["cocaine"],"offsets":[[741,748]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"8062","type":"Chemical","text":["norepinephrine"],"offsets":[[765,779]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"8063","type":"Chemical","text":["desipramine"],"offsets":[[833,844]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"8064","type":"Chemical","text":["lidocaine"],"offsets":[[886,895]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"8065","type":"Disease","text":["convulsions"],"offsets":[[904,915]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"8066","type":"Chemical","text":["cocaine"],"offsets":[[938,945]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"8067","type":"Disease","text":["convulsions"],"offsets":[[954,965]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"8068","type":"Chemical","text":["lidocaine"],"offsets":[[988,997]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"8069","type":"Chemical","text":["desipramine"],"offsets":[[1003,1014]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"8070","type":"Disease","text":["convulsive"],"offsets":[[1039,1049]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"8071","type":"Chemical","text":["lidocaine"],"offsets":[[1062,1071]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"8072","type":"Chemical","text":["cocaine"],"offsets":[[1076,1083]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"8073","type":"Chemical","text":["desipramine"],"offsets":[[1122,1133]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"8074","type":"Chemical","text":["desipramine"],"offsets":[[1234,1245]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"8075","type":"Chemical","text":["desipramine"],"offsets":[[1265,1276]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"8076","type":"Chemical","text":["lidocaine"],"offsets":[[1302,1311]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"8077","type":"Disease","text":["convulsions"],"offsets":[[1312,1323]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"8078","type":"Chemical","text":["Na"],"offsets":[[1339,1341]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"8079","type":"Chemical","text":["desipramine"],"offsets":[[1388,1399]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"8080","type":"Chemical","text":["cocaine"],"offsets":[[1468,1475]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"8081","type":"Chemical","text":["Desipramine"],"offsets":[[1527,1538]],"normalized":[{"db_name":"MESH","db_id":"D003891"}]},{"id":"8082","type":"Chemical","text":["lidocaine"],"offsets":[[1564,1573]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"8083","type":"Disease","text":["seizures"],"offsets":[[1574,1582]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"8084","type":"Chemical","text":["cocaine"],"offsets":[[1669,1676]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]}],"events":[],"coreferences":[],"relations":[{"id":"8085","type":"CID","arg1_id":"8054","arg2_id":"8051","normalized":[]},{"id":"8086","type":"CID","arg1_id":"8054","arg2_id":"8053","normalized":[]},{"id":"8087","type":"CID","arg1_id":"8054","arg2_id":"8065","normalized":[]},{"id":"8088","type":"CID","arg1_id":"8054","arg2_id":"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{"id":"8169","document_id":"16629641","passages":[{"id":"8170","type":"title","text":["Definition and management of anemia in patients infected with hepatitis C virus."],"offsets":[[0,80]]},{"id":"8171","type":"abstract","text":["Chronic infection with hepatitis C virus (HCV) can progress to cirrhosis, hepatocellular carcinoma, and end-stage liver disease. The current best treatment for HCV infection is combination therapy with pegylated interferon and ribavirin. Although this regimen produces sustained virologic responses (SVRs) in approximately 50% of patients, it can be associated with a potentially dose-limiting hemolytic anemia. Hemoglobin concentrations decrease mainly as a result of ribavirin-induced hemolysis, and this anemia can be problematic in patients with HCV infection, especially those who have comorbid renal or cardiovascular disorders. In general, anemia can increase the risk of morbidity and mortality, and may have negative effects on cerebral function and quality of life. Although ribavirin-associated anemia can be reversed by dose reduction or discontinuation, this approach compromises outcomes by significantly decreasing SVR rates. Recombinant human erythropoietin has been used to manage ribavirin-associated anemia but has other potential disadvantages. Viramidine, a liver-targeting prodrug of ribavirin, has the potential to maintain the virologic efficacy of ribavirin while decreasing the risk of hemolytic anemia in patients with chronic hepatitis C."],"offsets":[[81,1347]]}],"entities":[{"id":"8172","type":"Disease","text":["anemia"],"offsets":[[29,35]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"8173","type":"Disease","text":["infected with hepatitis C virus"],"offsets":[[48,79]],"normalized":[{"db_name":"MESH","db_id":"D006526"}]},{"id":"8174","type":"Disease","text":["Chronic infection with hepatitis C virus"],"offsets":[[81,121]],"normalized":[{"db_name":"MESH","db_id":"D019698"}]},{"id":"8175","type":"Disease","text":["cirrhosis"],"offsets":[[144,153]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"8176","type":"Disease","text":["hepatocellular carcinoma"],"offsets":[[155,179]],"normalized":[{"db_name":"MESH","db_id":"D006528"}]},{"id":"8177","type":"Disease","text":["end-stage liver disease"],"offsets":[[185,208]],"normalized":[{"db_name":"MESH","db_id":"D058625"}]},{"id":"8178","type":"Disease","text":["HCV infection"],"offsets":[[241,254]],"normalized":[{"db_name":"MESH","db_id":"D006526"}]},{"id":"8179","type":"Chemical","text":["interferon"],"offsets":[[293,303]],"normalized":[{"db_name":"MESH","db_id":"D007372"}]},{"id":"8180","type":"Chemical","text":["ribavirin"],"offsets":[[308,317]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"8181","type":"Disease","text":["hemolytic anemia"],"offsets":[[475,491]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"8182","type":"Chemical","text":["ribavirin"],"offsets":[[550,559]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"8183","type":"Disease","text":["hemolysis"],"offsets":[[568,577]],"normalized":[{"db_name":"MESH","db_id":"D006461"}]},{"id":"8184","type":"Disease","text":["anemia"],"offsets":[[588,594]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"8185","type":"Disease","text":["HCV infection"],"offsets":[[631,644]],"normalized":[{"db_name":"MESH","db_id":"D006526"}]},{"id":"8186","type":"Disease","text":["renal or cardiovascular disorders"],"offsets":[[681,714]],"normalized":[{"db_name":"MESH","db_id":"D007674"},{"db_name":"MESH","db_id":"D002318"}]},{"id":"8187","type":"Disease","text":["renal","disorders"],"offsets":[[681,686],[705,714]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"8188","type":"Disease","text":["cardiovascular disorders"],"offsets":[[690,714]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"8189","type":"Disease","text":["anemia"],"offsets":[[728,734]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"8190","type":"Chemical","text":["ribavirin"],"offsets":[[866,875]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"8191","type":"Disease","text":["anemia"],"offsets":[[887,893]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"8192","type":"Chemical","text":["ribavirin"],"offsets":[[1079,1088]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"8193","type":"Disease","text":["anemia"],"offsets":[[1100,1106]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"8194","type":"Chemical","text":["Viramidine"],"offsets":[[1146,1156]],"normalized":[{"db_name":"MESH","db_id":"C026956"}]},{"id":"8195","type":"Chemical","text":["ribavirin"],"offsets":[[1187,1196]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"8196","type":"Chemical","text":["ribavirin"],"offsets":[[1254,1263]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"8197","type":"Disease","text":["hemolytic anemia"],"offsets":[[1293,1309]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"8198","type":"Disease","text":["chronic hepatitis C"],"offsets":[[1327,1346]],"normalized":[{"db_name":"MESH","db_id":"D019698"}]}],"events":[],"coreferences":[],"relations":[{"id":"8199","type":"CID","arg1_id":"8180","arg2_id":"8181","normalized":[]},{"id":"8200","type":"CID","arg1_id":"8180","arg2_id":"8197","normalized":[]},{"id":"8201","type":"CID","arg1_id":"8182","arg2_id":"8181","normalized":[]},{"id":"8202","type":"CID","arg1_id":"8182","arg2_id":"8197","normalized":[]},{"id":"8203","type":"CID","arg1_id":"8190","arg2_id":"8181","normalized":[]},{"id":"8204","type":"CID","arg1_id":"8190","arg2_id":"8197","normalized":[]},{"id":"8205","type":"CID","arg1_id":"8192","arg2_id":"8181","normalized":[]},{"id":"8206","type":"CID","arg1_id":"8192","arg2_id":"8197","normalized":[]},{"id":"8207","type":"CID","arg1_id":"8195","arg2_id":"8181","normalized":[]},{"id":"8208","type":"CID","arg1_id":"8195","arg2_id":"8197","normalized":[]},{"id":"8209","type":"CID","arg1_id":"8196","arg2_id":"8181","normalized":[]},{"id":"8210","type":"CID","arg1_id":"8196","arg2_id":"8197","normalized":[]},{"id":"8211","type":"CID","arg1_id":"8179","arg2_id":"8181","normalized":[]},{"id":"8212","type":"CID","arg1_id":"8179","arg2_id":"8197","normalized":[]}]}
{"id":"8213","document_id":"16006300","passages":[{"id":"8214","type":"title","text":["Calcium carbonate toxicity: the updated milk-alkali syndrome; report of 3 cases and review of the literature."],"offsets":[[0,109]]},{"id":"8215","type":"abstract","text":["OBJECTIVE: To describe 3 patients with calcium carbonate-induced hypercalcemia and gain insights into the cause and management of the milk-alkali syndrome. METHODS: We report the clinical and laboratory data in 3 patients who presented with severe hypercalcemia (corrected serum calcium > or = 14 mg\/dL) and review the pertinent literature on milk-alkali syndrome. RESULTS: The 3 patients had acute renal insufficiency, relative metabolic alkalosis, and low parathyroid hormone (PTH), PTH-related peptide, and 1,25-dihydroxyvitamin D concentrations. No malignant lesion was found. Treatment included aggressive hydration and varied amounts of furosemide. The 2 patients with the higher serum calcium concentrations received pamidronate intravenously (60 and 30 mg, respectively), which caused severe hypocalcemia. Of the 3 patients, 2 were ingesting acceptable doses of elemental calcium (1 g and 2 g daily, respectively) in the form of calcium carbonate. In addition to our highlighted cases, we review the history, classification, pathophysiologic features, and treatment of milk-alkali syndrome and summarize the cases reported from early 1995 to November 2003. CONCLUSION: Milk-alkali syndrome may be a common cause of unexplained hypercalcemia and can be precipitated by small amounts of orally ingested calcium carbonate in susceptible persons. Treatment with hydration, furosemide, and discontinuation of the calcium and vitamin D source is adequate. Pamidronate treatment is associated with considerable risk for hypocalcemia, even in cases of initially severe hypercalcemia."],"offsets":[[110,1693]]}],"entities":[{"id":"8216","type":"Chemical","text":["Calcium carbonate"],"offsets":[[0,17]],"normalized":[{"db_name":"MESH","db_id":"D002119"}]},{"id":"8217","type":"Disease","text":["toxicity"],"offsets":[[18,26]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"8218","type":"Disease","text":["milk-alkali syndrome"],"offsets":[[40,60]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"8219","type":"Chemical","text":["calcium carbonate"],"offsets":[[149,166]],"normalized":[{"db_name":"MESH","db_id":"D002119"}]},{"id":"8220","type":"Disease","text":["hypercalcemia"],"offsets":[[175,188]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"8221","type":"Disease","text":["milk-alkali syndrome"],"offsets":[[244,264]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"8222","type":"Disease","text":["hypercalcemia"],"offsets":[[358,371]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"8223","type":"Chemical","text":["calcium"],"offsets":[[389,396]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"8224","type":"Disease","text":["milk-alkali syndrome"],"offsets":[[453,473]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"8225","type":"Disease","text":["acute renal insufficiency"],"offsets":[[503,528]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"8226","type":"Disease","text":["metabolic alkalosis"],"offsets":[[539,558]],"normalized":[{"db_name":"MESH","db_id":"D000471"}]},{"id":"8227","type":"Chemical","text":["1,25-dihydroxyvitamin D"],"offsets":[[620,643]],"normalized":[{"db_name":"MESH","db_id":"C097949"}]},{"id":"8228","type":"Chemical","text":["furosemide"],"offsets":[[753,763]],"normalized":[{"db_name":"MESH","db_id":"D005665"}]},{"id":"8229","type":"Chemical","text":["calcium"],"offsets":[[802,809]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"8230","type":"Chemical","text":["pamidronate"],"offsets":[[834,845]],"normalized":[{"db_name":"MESH","db_id":"C019248"}]},{"id":"8231","type":"Disease","text":["hypocalcemia"],"offsets":[[910,922]],"normalized":[{"db_name":"MESH","db_id":"D006996"}]},{"id":"8232","type":"Chemical","text":["calcium"],"offsets":[[990,997]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"8233","type":"Chemical","text":["calcium carbonate"],"offsets":[[1047,1064]],"normalized":[{"db_name":"MESH","db_id":"D002119"}]},{"id":"8234","type":"Disease","text":["milk-alkali syndrome"],"offsets":[[1187,1207]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"8235","type":"Disease","text":["Milk-alkali syndrome"],"offsets":[[1287,1307]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"8236","type":"Disease","text":["hypercalcemia"],"offsets":[[1345,1358]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"8237","type":"Chemical","text":["calcium carbonate"],"offsets":[[1419,1436]],"normalized":[{"db_name":"MESH","db_id":"D002119"}]},{"id":"8238","type":"Chemical","text":["furosemide"],"offsets":[[1487,1497]],"normalized":[{"db_name":"MESH","db_id":"D005665"}]},{"id":"8239","type":"Chemical","text":["calcium"],"offsets":[[1526,1533]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"8240","type":"Chemical","text":["vitamin D"],"offsets":[[1538,1547]],"normalized":[{"db_name":"MESH","db_id":"D014807"}]},{"id":"8241","type":"Chemical","text":["Pamidronate"],"offsets":[[1568,1579]],"normalized":[{"db_name":"MESH","db_id":"C019248"}]},{"id":"8242","type":"Disease","text":["hypocalcemia"],"offsets":[[1631,1643]],"normalized":[{"db_name":"MESH","db_id":"D006996"}]},{"id":"8243","type":"Disease","text":["hypercalcemia"],"offsets":[[1679,1692]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]}],"events":[],"coreferences":[],"relations":[{"id":"8244","type":"CID","arg1_id":"8230","arg2_id":"8231","normalized":[]},{"id":"8245","type":"CID","arg1_id":"8230","arg2_id":"8242","normalized":[]},{"id":"8246","type":"CID","arg1_id":"8241","arg2_id":"8231","normalized":[]},{"id":"8247","type":"CID","arg1_id":"8241","arg2_id":"8242","normalized":[]},{"id":"8248","type":"CID","arg1_id":"8216","arg2_id":"8218","normalized":[]},{"id":"8249","type":"CID","arg1_id":"8216","arg2_id":"8220","normalized":[]},{"id":"8250","type":"CID","arg1_id":"8216","arg2_id":"8221","normalized":[]},{"id":"8251","type":"CID","arg1_id":"8216","arg2_id":"8222","normalized":[]},{"id":"8252","type":"CID","arg1_id":"8216","arg2_id":"8224","normalized":[]},{"id":"8253","type":"CID","arg1_id":"8216","arg2_id":"8234","normalized":[]},{"id":"8254","type":"CID","arg1_id":"8216","arg2_id":"8235","normalized":[]},{"id":"8255","type":"CID","arg1_id":"8216","arg2_id":"8236","normalized":[]},{"id":"8256","type":"CID","arg1_id":"8216","arg2_id":"8243","normalized":[]},{"id":"8257","type":"CID","arg1_id":"8219","arg2_id":"8218","normalized":[]},{"id":"8258","type":"CID","arg1_id":"8219","arg2_id":"8220","normalized":[]},{"id":"8259","type":"CID","arg1_id":"8219","arg2_id":"8221","normalized":[]},{"id":"8260","type":"CID","arg1_id":"8219","arg2_id":"8222","normalized":[]},{"id":"8261","type":"CID","arg1_id":"8219","arg2_id":"8224","normalized":[]},{"id":"8262","type":"CID","arg1_id":"8219","arg2_id":"8234","normalized":[]},{"id":"8263","type":"CID","arg1_id":"8219","arg2_id":"8235","normalized":[]},{"id":"8264","type":"CID","arg1_id":"8219","arg2_id":"8236","normalized":[]},{"id":"8265","type":"CID","arg1_id":"8219","arg2_id":"8243","normalized":[]},{"id":"8266","type":"CID","arg1_id":"8233","arg2_id":"8218","normalized":[]},{"id":"8267","type":"CID","arg1_id":"8233","arg2_id":"8220","normalized":[]},{"id":"8268","type":"CID","arg1_id":"8233","arg2_id":"8221","normalized":[]},{"id":"8269","type":"CID","arg1_id":"8233","arg2_id":"8222","normalized":[]},{"id":"8270","type":"CID","arg1_id":"8233","arg2_id":"8224","normalized":[]},{"id":"8271","type":"CID","arg1_id":"8233","arg2_id":"8234","normalized":[]},{"id":"8272","type":"CID","arg1_id":"8233","arg2_id":"8235","normalized":[]},{"id":"8273","type":"CID","arg1_id":"8233","arg2_id":"8236","normalized":[]},{"id":"8274","type":"CID","arg1_id":"8233","arg2_id":"8243","normalized":[]},{"id":"8275","type":"CID","arg1_id":"8237","arg2_id":"8218","normalized":[]},{"id":"8276","type":"CID","arg1_id":"8237","arg2_id":"8220","normalized":[]},{"id":"8277","type":"CID","arg1_id":"8237","arg2_id":"8221","normalized":[]},{"id":"8278","type":"CID","arg1_id":"8237","arg2_id":"8222","normalized":[]},{"id":"8279","type":"CID","arg1_id":"8237","arg2_id":"8224","normalized":[]},{"id":"8280","type":"CID","arg1_id":"8237","arg2_id":"8234","normalized":[]},{"id":"8281","type":"CID","arg1_id":"8237","arg2_id":"8235","normalized":[]},{"id":"8282","type":"CID","arg1_id":"8237","arg2_id":"8236","normalized":[]},{"id":"8283","type":"CID","arg1_id":"8237","arg2_id":"8243","normalized":[]}]}
{"id":"8284","document_id":"11705128","passages":[{"id":"8285","type":"title","text":["Management strategies for ribavirin-induced hemolytic anemia in the treatment of hepatitis C: clinical and economic implications."],"offsets":[[0,129]]},{"id":"8286","type":"abstract","text":["OBJECTIVES: Recently published studies have demonstrated increased efficacy and cost-effectiveness of combination therapy with interferon and alpha-2b\/ribavirin compared with interferon-alpha monotherapy in the treatment of chronic hepatitis C (CHC). Combination therapy is associated with a clinically important adverse effect: ribavirin-induced hemolytic anemia (RIHA). The objective of this study was to evaluate the direct health-care costs and management of RIHA during treatment of CHC in a clinical trial setting. METHODS: A systematic literature review was conducted to synthesize information on the incidence and management of RIHA. Decision-analytic techniques were used to estimate the cost of treating RIHA. Uncertainty was evaluated using sensitivity analyses. RESULTS: RIHA, defined as a reduction in hemoglobin to less than 100 g\/L, occurs in approximately 7% to 9% of patients treated with combination therapy. The standard of care for management of RIHA is reduction or discontinuation of the ribavirin dosage. We estimated the direct cost of treating clinically significant RIHA to be  170 per patient receiving combination therapy per 48-week treatment course (range  68- 692). The results of the one-way sensitivity analyses ranged from  57 to  317. In comparison, the cost of 48 weeks of combination therapy is  16,459. CONCLUSIONS: The direct cost of treating clinically significant RIHA is 1% ( 170\/ 16,459) of drug treatment costs. Questions remain about the optimal dose of ribavirin and the incidence of RIHA in a real-world population. Despite these uncertainties, this initial evaluation of the direct cost of treating RIHA provides an estimate of the cost and management implications of this clinically important adverse effect."],"offsets":[[130,1887]]}],"entities":[{"id":"8287","type":"Chemical","text":["ribavirin"],"offsets":[[26,35]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"8288","type":"Disease","text":["hemolytic anemia"],"offsets":[[44,60]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"8289","type":"Disease","text":["hepatitis C"],"offsets":[[81,92]],"normalized":[{"db_name":"MESH","db_id":"D006526"}]},{"id":"8290","type":"Chemical","text":["ribavirin"],"offsets":[[281,290]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"8291","type":"Chemical","text":["interferon-alpha"],"offsets":[[305,321]],"normalized":[{"db_name":"MESH","db_id":"D016898"}]},{"id":"8292","type":"Disease","text":["chronic hepatitis 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{"id":"8381","document_id":"6540303","passages":[{"id":"8382","type":"title","text":["Effects of amine pretreatment on ketamine catatonia in pinealectomized or hypophysectomized animals."],"offsets":[[0,100]]},{"id":"8383","type":"abstract","text":["The present studies were designed to clarify the role of catecholamines and pineal idolamines on ketamine-induced catatonia in the intact, pinealectomized or hypophysectomized chick and rat. In the pinealectomized chick, pretreatment with dopamine increased the duration of catatonia (DOC) after ketamine, but pretreatment with norepinephrine did not. The pineal indolamines exhibited mixed actions. Serotonin and N-acetyl serotonin which augmented ketamine DOC, did not do so in the absence of the pineal gland, whereas melatonin potentiated the ketamine DOC in both the intact and pinealectomized chick. Ketamine was more potent in the hypophysectomized chick and the circadian rhythm noted in the intact chick was absent; furthermore, melatonin did not augment the ketamine DOC whereas dopamine continued to do so. This study did not demonstrate a species difference regarding the role of the amines on the pineal in spite of the immature blood-brain barrier in the young chick and the intact barrier in the rat. In addition, these data indicate a direct role of the pituitary in the augmentation of ketamine DOC induced by melatonin. Furthermore, dopamine appeared to act on systems more closely involved with the induction of ketamine catatonia rather than directly on the pituitary."],"offsets":[[101,1389]]}],"entities":[{"id":"8384","type":"Chemical","text":["amine"],"offsets":[[11,16]],"normalized":[{"db_name":"MESH","db_id":"D000588"}]},{"id":"8385","type":"Chemical","text":["ketamine"],"offsets":[[33,41]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"8386","type":"Disease","text":["catatonia"],"offsets":[[42,51]],"normalized":[{"db_name":"MESH","db_id":"D002389"}]},{"id":"8387","type":"Chemical","text":["catecholamines"],"offsets":[[158,172]],"normalized":[{"db_name":"MESH","db_id":"D002395"}]},{"id":"8388","type":"Chemical","text":["ketamine"],"offsets":[[198,206]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"8389","type":"Disease","text":["catatonia"],"offsets":[[215,224]],"normalized":[{"db_name":"MESH","db_id":"D002389"}]},{"id":"8390","type":"Chemical","text":["dopamine"],"offsets":[[340,348]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"8391","type":"Disease","text":["catatonia"],"offsets":[[375,384]],"normalized":[{"db_name":"MESH","db_id":"D002389"}]},{"id":"8392","type":"Chemical","text":["ketamine"],"offsets":[[397,405]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"8393","type":"Chemical","text":["norepinephrine"],"offsets":[[429,443]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"8394","type":"Chemical","text":["Serotonin"],"offsets":[[501,510]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"8395","type":"Chemical","text":["N-acetyl 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{"id":"8473","document_id":"3057041","passages":[{"id":"8474","type":"title","text":["Multicenter, double-blind, multiple-dose, parallel-groups efficacy and safety trial of azelastine, chlorpheniramine, and placebo in the treatment of spring allergic rhinitis."],"offsets":[[0,174]]},{"id":"8475","type":"abstract","text":["Azelastine, a novel antiallergic medication, was compared with chlorpheniramine maleate and placebo for efficacy and safety in the treatment of spring allergic rhinitis in a multicenter, double-blind, multiple-dose, parallel-groups study. One hundred fifty-five subjects participated. Subjects ranged in age from 18 to 60 years of age and had at least a 2-year history of spring allergic rhinitis, confirmed by positive skin test to spring aeroallergens. Medications were given four times daily; the azelastine groups received 0.5, 1.0, or 2.0 mg in the morning and evening with placebo in the early and late afternoon; the chlorpheniramine group received 4.0 mg four times daily. Daily subject symptom cards were completed during a screening period to assess pretreatment symptoms and during a 4-week treatment period while subjects received study medications. Individual symptoms, total symptoms, and major symptoms were compared to determine efficacy of medication. Elicited, volunteered, and observed adverse experiences were recorded for each subject and compared among groups. Vital signs, body weights, serum chemistry values, complete blood cell counts, urine studies, and electrocardiograms were obtained for each subject and compared among groups. Symptoms relief in the group receiving the highest concentration of azelastine (2.0 mg twice daily) was statistically greater than in the placebo group during all weeks of the study. Lower doses of azelastine were statistically more effective than placebo only during portions of the first 3 weeks of the study. In contrast, although the chlorpheniramine group did have fewer symptoms than the placebo group during the study, the difference never reached statistical significance during any week of the study. There were no serious side effects in any of the treatment groups. Drowsiness and altered taste perception were increased significantly over placebo only in the high-dose azelastine group. Azelastine appears to be a safe, efficacious medication for seasonal allergic rhinitis."],"offsets":[[175,2219]]}],"entities":[{"id":"8476","type":"Chemical","text":["azelastine"],"offsets":[[87,97]],"normalized":[{"db_name":"MESH","db_id":"C020976"}]},{"id":"8477","type":"Chemical","text":["chlorpheniramine"],"offsets":[[99,115]],"normalized":[{"db_name":"MESH","db_id":"D002744"}]},{"id":"8478","type":"Disease","text":["spring allergic rhinitis"],"offsets":[[149,173]],"normalized":[{"db_name":"MESH","db_id":"D006255"}]},{"id":"8479","type":"Chemical","text":["Azelastine"],"offsets":[[175,185]],"normalized":[{"db_name":"MESH","db_id":"C020976"}]},{"id":"8480","type":"Chemical","text":["chlorpheniramine maleate"],"offsets":[[238,262]],"normalized":[{"db_name":"MESH","db_id":"D002744"}]},{"id":"8481","type":"Disease","text":["spring allergic rhinitis"],"offsets":[[319,343]],"normalized":[{"db_name":"MESH","db_id":"D006255"}]},{"id":"8482","type":"Disease","text":["spring allergic rhinitis"],"offsets":[[547,571]],"normalized":[{"db_name":"MESH","db_id":"D006255"}]},{"id":"8483","type":"Chemical","text":["azelastine"],"offsets":[[675,685]],"normalized":[{"db_name":"MESH","db_id":"C020976"}]},{"id":"8484","type":"Chemical","text":["chlorpheniramine"],"offsets":[[799,815]],"normalized":[{"db_name":"MESH","db_id":"D002744"}]},{"id":"8485","type":"Chemical","text":["azelastine"],"offsets":[[1501,1511]],"normalized":[{"db_name":"MESH","db_id":"C020976"}]},{"id":"8486","type":"Chemical","text":["azelastine"],"offsets":[[1631,1641]],"normalized":[{"db_name":"MESH","db_id":"C020976"}]},{"id":"8487","type":"Chemical","text":["chlorpheniramine"],"offsets":[[1771,1787]],"normalized":[{"db_name":"MESH","db_id":"D002744"}]},{"id":"8488","type":"Disease","text":["Drowsiness"],"offsets":[[2010,2020]],"normalized":[{"db_name":"MESH","db_id":"D006970"}]},{"id":"8489","type":"Disease","text":["altered taste perception"],"offsets":[[2025,2049]],"normalized":[{"db_name":"MESH","db_id":"D013651"}]},{"id":"8490","type":"Chemical","text":["azelastine"],"offsets":[[2114,2124]],"normalized":[{"db_name":"MESH","db_id":"C020976"}]},{"id":"8491","type":"Chemical","text":["Azelastine"],"offsets":[[2132,2142]],"normalized":[{"db_name":"MESH","db_id":"C020976"}]},{"id":"8492","type":"Disease","text":["seasonal allergic rhinitis"],"offsets":[[2192,2218]],"normalized":[{"db_name":"MESH","db_id":"D006255"}]}],"events":[],"coreferences":[],"relations":[{"id":"8493","type":"CID","arg1_id":"8476","arg2_id":"8488","normalized":[]},{"id":"8494","type":"CID","arg1_id":"8479","arg2_id":"8488","normalized":[]},{"id":"8495","type":"CID","arg1_id":"8483","arg2_id":"8488","normalized":[]},{"id":"8496","type":"CID","arg1_id":"8485","arg2_id":"8488","normalized":[]},{"id":"8497","type":"CID","arg1_id":"8486","arg2_id":"8488","normalized":[]},{"id":"8498","type":"CID","arg1_id":"8490","arg2_id":"8488","normalized":[]},{"id":"8499","type":"CID","arg1_id":"8491","arg2_id":"8488","normalized":[]},{"id":"8500","type":"CID","arg1_id":"8476","arg2_id":"8489","normalized":[]},{"id":"8501","type":"CID","arg1_id":"8479","arg2_id":"8489","normalized":[]},{"id":"8502","type":"CID","arg1_id":"8483","arg2_id":"8489","normalized":[]},{"id":"8503","type":"CID","arg1_id":"8485","arg2_id":"8489","normalized":[]},{"id":"8504","type":"CID","arg1_id":"8486","arg2_id":"8489","normalized":[]},{"id":"8505","type":"CID","arg1_id":"8490","arg2_id":"8489","normalized":[]},{"id":"8506","type":"CID","arg1_id":"8491","arg2_id":"8489","normalized":[]}]}
{"id":"8507","document_id":"625456","passages":[{"id":"8508","type":"title","text":["Obsolete but dangerous antacid preparations."],"offsets":[[0,44]]},{"id":"8509","type":"abstract","text":["One case of acute hypercalcaemia and two of recurrent nephrolithiasis are reported in patients who had regularly consumed large amounts of calcium carbon-ate-sodium bicarbonate powders for more than 20 years. The powders had been obtained from pharmacists unknown to the patients' medical practitioners. It is suggested that these preparations were responsible for the patient's problems, and that such powders should no longer be freely obtainable."],"offsets":[[45,494]]}],"entities":[{"id":"8510","type":"Disease","text":["hypercalcaemia"],"offsets":[[63,77]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"8511","type":"Disease","text":["nephrolithiasis"],"offsets":[[99,114]],"normalized":[{"db_name":"MESH","db_id":"D053040"}]},{"id":"8512","type":"Chemical","text":["calcium carbon-ate"],"offsets":[[184,202]],"normalized":[{"db_name":"MESH","db_id":"D002119"}]},{"id":"8513","type":"Chemical","text":["sodium bicarbonate"],"offsets":[[203,221]],"normalized":[{"db_name":"MESH","db_id":"D017693"}]}],"events":[],"coreferences":[],"relations":[{"id":"8514","type":"CID","arg1_id":"8512","arg2_id":"8510","normalized":[]},{"id":"8515","type":"CID","arg1_id":"8513","arg2_id":"8511","normalized":[]},{"id":"8516","type":"CID","arg1_id":"8513","arg2_id":"8510","normalized":[]},{"id":"8517","type":"CID","arg1_id":"8512","arg2_id":"8511","normalized":[]}]}
{"id":"8518","document_id":"7910951","passages":[{"id":"8519","type":"title","text":["Prolonged paralysis due to nondepolarizing neuromuscular blocking agents and corticosteroids."],"offsets":[[0,93]]},{"id":"8520","type":"abstract","text":["The long-term use of nondepolarizing neuromuscular blocking agents (ND-NMBA) has recently been implicated as a cause of prolonged muscle weakness, although the site of the lesion and the predisposing factors have been unclear. We report 3 patients (age 37-52 years) with acute respiratory insufficiency who developed prolonged weakness following the discontinuation of ND-NMBAs. Two patients also received intravenous corticosteroids. Renal function was normal but hepatic function was impaired in all patients, and all had acidosis. Electrophysiologic studies revealed low amplitude compound motor action potentials, normal sensory studies, and fibrillations. Repetitive stimulation at 2 Hz showed a decremental response in 2 patients. The serum vecuronium level measured in 1 patient 14 days after the drug had been discontinued was 172 ng\/mL. A muscle biopsy in this patient showed loss of thick, myosin filaments. The weakness in these patients is due to pathology at both the neuromuscular junction (most likely due to ND-NMBA) and muscle (most likely due to corticosteroids). Hepatic dysfunction and acidosis are contributing risk factors."],"offsets":[[94,1239]]}],"entities":[{"id":"8521","type":"Disease","text":["paralysis"],"offsets":[[10,19]],"normalized":[{"db_name":"MESH","db_id":"D010243"}]},{"id":"8522","type":"Chemical","text":["nondepolarizing neuromuscular blocking agents"],"offsets":[[27,72]],"normalized":[{"db_name":"MESH","db_id":"D003473"}]},{"id":"8523","type":"Chemical","text":["corticosteroids"],"offsets":[[77,92]],"normalized":[{"db_name":"MESH","db_id":"D000305"}]},{"id":"8524","type":"Chemical","text":["nondepolarizing neuromuscular blocking agents"],"offsets":[[115,160]],"normalized":[{"db_name":"MESH","db_id":"D003473"}]},{"id":"8525","type":"Chemical","text":["ND-NMBA"],"offsets":[[162,169]],"normalized":[{"db_name":"MESH","db_id":"D003473"}]},{"id":"8526","type":"Disease","text":["muscle weakness"],"offsets":[[224,239]],"normalized":[{"db_name":"MESH","db_id":"D018908"}]},{"id":"8527","type":"Disease","text":["respiratory insufficiency"],"offsets":[[371,396]],"normalized":[{"db_name":"MESH","db_id":"D012131"}]},{"id":"8528","type":"Disease","text":["weakness"],"offsets":[[421,429]],"normalized":[{"db_name":"MESH","db_id":"D018908"}]},{"id":"8529","type":"Chemical","text":["ND-NMBAs"],"offsets":[[463,471]],"normalized":[{"db_name":"MESH","db_id":"D003473"}]},{"id":"8530","type":"Chemical","text":["corticosteroids"],"offsets":[[512,527]],"normalized":[{"db_name":"MESH","db_id":"D000305"}]},{"id":"8531","type":"Disease","text":["acidosis"],"offsets":[[618,626]],"normalized":[{"db_name":"MESH","db_id":"D000138"}]},{"id":"8532","type":"Chemical","text":["vecuronium"],"offsets":[[841,851]],"normalized":[{"db_name":"MESH","db_id":"D014673"}]},{"id":"8533","type":"Disease","text":["loss of thick, myosin filaments"],"offsets":[[979,1010]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"8534","type":"Disease","text":["weakness"],"offsets":[[1016,1024]],"normalized":[{"db_name":"MESH","db_id":"D018908"}]},{"id":"8535","type":"Disease","text":["pathology at both the neuromuscular junction"],"offsets":[[1053,1097]],"normalized":[{"db_name":"MESH","db_id":"D009468"}]},{"id":"8536","type":"Chemical","text":["ND-NMBA"],"offsets":[[1118,1125]],"normalized":[{"db_name":"MESH","db_id":"D003473"}]},{"id":"8537","type":"Chemical","text":["corticosteroids"],"offsets":[[1158,1173]],"normalized":[{"db_name":"MESH","db_id":"D000305"}]},{"id":"8538","type":"Disease","text":["Hepatic dysfunction"],"offsets":[[1176,1195]],"normalized":[{"db_name":"MESH","db_id":"D008107"}]},{"id":"8539","type":"Disease","text":["acidosis"],"offsets":[[1200,1208]],"normalized":[{"db_name":"MESH","db_id":"D000138"}]}],"events":[],"coreferences":[],"relations":[{"id":"8540","type":"CID","arg1_id":"8522","arg2_id":"8526","normalized":[]},{"id":"8541","type":"CID","arg1_id":"8522","arg2_id":"8528","normalized":[]},{"id":"8542","type":"CID","arg1_id":"8522","arg2_id":"8534","normalized":[]},{"id":"8543","type":"CID","arg1_id":"8524","arg2_id":"8526","normalized":[]},{"id":"8544","type":"CID","arg1_id":"8524","arg2_id":"8528","normalized":[]},{"id":"8545","type":"CID","arg1_id":"8524","arg2_id":"8534","normalized":[]},{"id":"8546","type":"CID","arg1_id":"8525","arg2_id":"8526","normalized":[]},{"id":"8547","type":"CID","arg1_id":"8525","arg2_id":"8528","normalized":[]},{"id":"8548","type":"CID","arg1_id":"8525","arg2_id":"8534","normalized":[]},{"id":"8549","type":"CID","arg1_id":"8529","arg2_id":"8526","normalized":[]},{"id":"8550","type":"CID","arg1_id":"8529","arg2_id":"8528","normalized":[]},{"id":"8551","type":"CID","arg1_id":"8529","arg2_id":"8534","normalized":[]},{"id":"8552","type":"CID","arg1_id":"8536","arg2_id":"8526","normalized":[]},{"id":"8553","type":"CID","arg1_id":"8536","arg2_id":"8528","normalized":[]},{"id":"8554","type":"CID","arg1_id":"8536","arg2_id":"8534","normalized":[]},{"id":"8555","type":"CID","arg1_id":"8523","arg2_id":"8533","normalized":[]},{"id":"8556","type":"CID","arg1_id":"8530","arg2_id":"8533","normalized":[]},{"id":"8557","type":"CID","arg1_id":"8537","arg2_id":"8533","normalized":[]},{"id":"8558","type":"CID","arg1_id":"8522","arg2_id":"8535","normalized":[]},{"id":"8559","type":"CID","arg1_id":"8524","arg2_id":"8535","normalized":[]},{"id":"8560","type":"CID","arg1_id":"8525","arg2_id":"8535","normalized":[]},{"id":"8561","type":"CID","arg1_id":"8529","arg2_id":"8535","normalized":[]},{"id":"8562","type":"CID","arg1_id":"8536","arg2_id":"8535","normalized":[]}]}
{"id":"8563","document_id":"7752389","passages":[{"id":"8564","type":"title","text":["Prostaglandin E2-induced bladder hyperactivity in normal, conscious rats: involvement of tachykinins?"],"offsets":[[0,101]]},{"id":"8565","type":"abstract","text":["In normal conscious rats investigated by continuous cystometry, intravesically instilled prostaglandin (PG) E2 facilitated micturition and increased basal intravesical pressure. The effect was attenuated by both the NK1 receptor selective antagonist RP 67,580 and the NK2 receptor selective antagonist SR 48,968, given intra-arterially, suggesting that it was mediated by stimulation of both NK1 and NK2 receptors. Intra-arterially given PGE2 produced a distinct increase in bladder pressure before initiating a micturition reflex, indicating that the PG had a direct contractant effect on the detrusor smooth muscle. The effect of intra-arterial PGE2 could not be blocked by intra-arterial RP 67,580 or SR 48,968, which opens the possibility that the micturition reflex elicited by intra-arterial PGE2 was mediated by pathways other than the reflex initiated when the PG was given intravesically. The present results thus suggest that intra-arterial PGE2, given near the bladder, may initiate micturition in the normal rat chiefly by directly contracting the smooth muscle of the detrusor. However, when given intravesically, PGE2 may stimulate micturition by releasing tachykinins from nerves in and\/or immediately below the urothelium. These tachykinins, in turn, initiate a micturition reflex by stimulating NK1 and NK2 receptors. Prostanoids may, via release of tachykinins, contribute to both urge and bladder hyperactivity seen in inflammatory conditions of the lower urinary tract."],"offsets":[[102,1591]]}],"entities":[{"id":"8566","type":"Chemical","text":["Prostaglandin E2"],"offsets":[[0,16]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"8567","type":"Disease","text":["bladder hyperactivity"],"offsets":[[25,46]],"normalized":[{"db_name":"MESH","db_id":"D053201"}]},{"id":"8568","type":"Chemical","text":["tachykinins"],"offsets":[[89,100]],"normalized":[{"db_name":"MESH","db_id":"D015320"}]},{"id":"8569","type":"Chemical","text":["prostaglandin (PG) E2"],"offsets":[[191,212]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"8570","type":"Chemical","text":["RP 67,580"],"offsets":[[352,361]],"normalized":[{"db_name":"MESH","db_id":"C071693"}]},{"id":"8571","type":"Chemical","text":["SR 48,968"],"offsets":[[404,413]],"normalized":[{"db_name":"MESH","db_id":"C073839"}]},{"id":"8572","type":"Chemical","text":["PGE2"],"offsets":[[540,544]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"8573","type":"Chemical","text":["PG"],"offsets":[[654,656]],"normalized":[{"db_name":"MESH","db_id":"D011453"}]},{"id":"8574","type":"Chemical","text":["PGE2"],"offsets":[[749,753]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"8575","type":"Chemical","text":["RP 67,580"],"offsets":[[793,802]],"normalized":[{"db_name":"MESH","db_id":"C071693"}]},{"id":"8576","type":"Chemical","text":["SR 48,968"],"offsets":[[806,815]],"normalized":[{"db_name":"MESH","db_id":"C073839"}]},{"id":"8577","type":"Chemical","text":["PGE2"],"offsets":[[900,904]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"8578","type":"Chemical","text":["PG"],"offsets":[[971,973]],"normalized":[{"db_name":"MESH","db_id":"D011453"}]},{"id":"8579","type":"Chemical","text":["PGE2"],"offsets":[[1053,1057]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"8580","type":"Chemical","text":["PGE2"],"offsets":[[1229,1233]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"8581","type":"Chemical","text":["tachykinins"],"offsets":[[1273,1284]],"normalized":[{"db_name":"MESH","db_id":"D015320"}]},{"id":"8582","type":"Chemical","text":["tachykinins"],"offsets":[[1347,1358]],"normalized":[{"db_name":"MESH","db_id":"D015320"}]},{"id":"8583","type":"Chemical","text":["Prostanoids"],"offsets":[[1437,1448]],"normalized":[{"db_name":"MESH","db_id":"D011453"}]},{"id":"8584","type":"Chemical","text":["tachykinins"],"offsets":[[1469,1480]],"normalized":[{"db_name":"MESH","db_id":"D015320"}]},{"id":"8585","type":"Disease","text":["bladder hyperactivity"],"offsets":[[1510,1531]],"normalized":[{"db_name":"MESH","db_id":"D053201"}]}],"events":[],"coreferences":[],"relations":[{"id":"8586","type":"CID","arg1_id":"8566","arg2_id":"8567","normalized":[]},{"id":"8587","type":"CID","arg1_id":"8566","arg2_id":"8585","normalized":[]},{"id":"8588","type":"CID","arg1_id":"8569","arg2_id":"8567","normalized":[]},{"id":"8589","type":"CID","arg1_id":"8569","arg2_id":"8585","normalized":[]},{"id":"8590","type":"CID","arg1_id":"8572","arg2_id":"8567","normalized":[]},{"id":"8591","type":"CID","arg1_id":"8572","arg2_id":"8585","normalized":[]},{"id":"8592","type":"CID","arg1_id":"8574","arg2_id":"8567","normalized":[]},{"id":"8593","type":"CID","arg1_id":"8574","arg2_id":"8585","normalized":[]},{"id":"8594","type":"CID","arg1_id":"8577","arg2_id":"8567","normalized":[]},{"id":"8595","type":"CID","arg1_id":"8577","arg2_id":"8585","normalized":[]},{"id":"8596","type":"CID","arg1_id":"8579","arg2_id":"8567","normalized":[]},{"id":"8597","type":"CID","arg1_id":"8579","arg2_id":"8585","normalized":[]},{"id":"8598","type":"CID","arg1_id":"8580","arg2_id":"8567","normalized":[]},{"id":"8599","type":"CID","arg1_id":"8580","arg2_id":"8585","normalized":[]}]}
{"id":"8600","document_id":"6942642","passages":[{"id":"8601","type":"title","text":["Thiazide diuretics, hypokalemia and cardiac arrhythmias."],"offsets":[[0,56]]},{"id":"8602","type":"abstract","text":["Thiazide diuretics are widely accepted as the cornerstone of antihypertensive treatment programs. Hypokalemia is a commonly encountered metabolic consequence of chronic thiazide therapy. We treated 38 patients (22 low renin, 16 normal renin) with moderate diastolic hypertension with hydrochlorothiazide (HCTC) administered on a twice daily schedule. Initial dose was 50 mg and the dose was increased at monthly intervals to 100 mg, 150 mg and 200 mg daily until blood pressure normalized. The serum K during the control period was 4.5 +\/- 0.2 mEq\/l an on 50, 100, 150 and 200 mg HCTZ daily 3.9 +\/- 0.3, 3.4 +\/- 0.2, 2.9 +\/- 0.2, and 2.4 +\/- 0.3 mEq\/l, respectively. Corresponding figures for whole body K were 4107 +\/- 208, 3722 +\/- 319, 3628 +\/- 257, 3551 +\/- 336, and 3269 +\/- 380 mEq, respectively. In 13 patients we observed the effects of HCTZ therapy (100 mg daily) on the occurrence of PVC's during rest as well as during static and dynamic exercise. During rest we observed 0.6 +\/- 0.08 PVC beats\/min +\/- SEM and during static and dynamic exercise 0.6 +\/- 0.06 and 0.8 +\/- 0.15, respectively. Corresponding figures during HCTZ therapy 100 mg daily were 1.4 +\/- 0.1, 3.6 +\/- 0.7 and 5.7 4\/- 0.8, respectively. The occurrence of PVC's correlated significantly with the fall in serum K+ observed r = 0.72, p less than 0.001. In conclusion we found that thiazide diuretics cause hypokalemia and depletion of body potassium. The more profound hypokalemia, the greater the propensity for the occurrence of PVC's."],"offsets":[[57,1572]]}],"entities":[{"id":"8603","type":"Chemical","text":["Thiazide"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D049971"}]},{"id":"8604","type":"Disease","text":["hypokalemia"],"offsets":[[20,31]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"8605","type":"Disease","text":["cardiac arrhythmias"],"offsets":[[36,55]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"8606","type":"Chemical","text":["Thiazide"],"offsets":[[57,65]],"normalized":[{"db_name":"MESH","db_id":"D049971"}]},{"id":"8607","type":"Disease","text":["Hypokalemia"],"offsets":[[155,166]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"8608","type":"Chemical","text":["thiazide"],"offsets":[[226,234]],"normalized":[{"db_name":"MESH","db_id":"D049971"}]},{"id":"8609","type":"Disease","text":["diastolic hypertension"],"offsets":[[313,335]],"normalized":[{"db_name":"MESH","db_id":"C563897"}]},{"id":"8610","type":"Chemical","text":["hydrochlorothiazide"],"offsets":[[341,360]],"normalized":[{"db_name":"MESH","db_id":"D006852"}]},{"id":"8611","type":"Chemical","text":["HCTC"],"offsets":[[362,366]],"normalized":[{"db_name":"MESH","db_id":"D006852"}]},{"id":"8612","type":"Chemical","text":["K"],"offsets":[[557,558]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"8613","type":"Chemical","text":["HCTZ"],"offsets":[[637,641]],"normalized":[{"db_name":"MESH","db_id":"D006852"}]},{"id":"8614","type":"Chemical","text":["K"],"offsets":[[761,762]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"8615","type":"Chemical","text":["HCTZ"],"offsets":[[902,906]],"normalized":[{"db_name":"MESH","db_id":"D006852"}]},{"id":"8616","type":"Chemical","text":["HCTZ"],"offsets":[[1188,1192]],"normalized":[{"db_name":"MESH","db_id":"D006852"}]},{"id":"8617","type":"Chemical","text":["K"],"offsets":[[1347,1348]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"8618","type":"Chemical","text":["thiazide"],"offsets":[[1416,1424]],"normalized":[{"db_name":"MESH","db_id":"D049971"}]},{"id":"8619","type":"Disease","text":["hypokalemia"],"offsets":[[1441,1452]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"8620","type":"Chemical","text":["potassium"],"offsets":[[1475,1484]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"8621","type":"Disease","text":["hypokalemia"],"offsets":[[1504,1515]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]}],"events":[],"coreferences":[],"relations":[{"id":"8622","type":"CID","arg1_id":"8610","arg2_id":"8604","normalized":[]},{"id":"8623","type":"CID","arg1_id":"8610","arg2_id":"8607","normalized":[]},{"id":"8624","type":"CID","arg1_id":"8610","arg2_id":"8619","normalized":[]},{"id":"8625","type":"CID","arg1_id":"8610","arg2_id":"8621","normalized":[]},{"id":"8626","type":"CID","arg1_id":"8611","arg2_id":"8604","normalized":[]},{"id":"8627","type":"CID","arg1_id":"8611","arg2_id":"8607","normalized":[]},{"id":"8628","type":"CID","arg1_id":"8611","arg2_id":"8619","normalized":[]},{"id":"8629","type":"CID","arg1_id":"8611","arg2_id":"8621","normalized":[]},{"id":"8630","type":"CID","arg1_id":"8613","arg2_id":"8604","normalized":[]},{"id":"8631","type":"CID","arg1_id":"8613","arg2_id":"8607","normalized":[]},{"id":"8632","type":"CID","arg1_id":"8613","arg2_id":"8619","normalized":[]},{"id":"8633","type":"CID","arg1_id":"8613","arg2_id":"8621","normalized":[]},{"id":"8634","type":"CID","arg1_id":"8615","arg2_id":"8604","normalized":[]},{"id":"8635","type":"CID","arg1_id":"8615","arg2_id":"8607","normalized":[]},{"id":"8636","type":"CID","arg1_id":"8615","arg2_id":"8619","normalized":[]},{"id":"8637","type":"CID","arg1_id":"8615","arg2_id":"8621","normalized":[]},{"id":"8638","type":"CID","arg1_id":"8616","arg2_id":"8604","normalized":[]},{"id":"8639","type":"CID","arg1_id":"8616","arg2_id":"8607","normalized":[]},{"id":"8640","type":"CID","arg1_id":"8616","arg2_id":"8619","normalized":[]},{"id":"8641","type":"CID","arg1_id":"8616","arg2_id":"8621","normalized":[]},{"id":"8642","type":"CID","arg1_id":"8610","arg2_id":"8605","normalized":[]},{"id":"8643","type":"CID","arg1_id":"8611","arg2_id":"8605","normalized":[]},{"id":"8644","type":"CID","arg1_id":"8613","arg2_id":"8605","normalized":[]},{"id":"8645","type":"CID","arg1_id":"8615","arg2_id":"8605","normalized":[]},{"id":"8646","type":"CID","arg1_id":"8616","arg2_id":"8605","normalized":[]}]}
{"id":"8647","document_id":"3732088","passages":[{"id":"8648","type":"title","text":["Diuretics, potassium and arrhythmias in hypertensive coronary disease."],"offsets":[[0,70]]},{"id":"8649","type":"abstract","text":["It has been proposed that modest changes in plasma potassium can alter the tendency towards cardiac arrhythmias. If this were so, patients with coronary artery disease might be especially susceptible. Thus, myocardial electrical excitability was measured in patients with mild essential hypertension and known coronary artery disease after 8 weeks of treatment with a potassium-conserving diuretic (amiloride) and a similar period on a potassium-losing diuretic (chlorthalidone) in a randomised study. Plasma potassium concentrations were on average 1 mmol\/L lower during the chlorthalidone phase compared to amiloride therapy. Blood pressure and volume states as assessed by bodyweight, plasma renin and noradrenaline (norepinephrine) concentrations were similar on the 2 regimens. Compared to amiloride treatment, the chlorthalidone phase was associated with an increased frequency of ventricular ectopic beats (24-hour Holter monitoring) and a higher Lown grading, increased upslope and duration of the monophasic action potential, prolonged ventricular effective refractory period, and increased electrical instability during programmed ventricular stimulation. The above results indicate that because potassium-losing diuretic therapy can increase myocardial electrical excitability in patients with ischaemic heart disease, even minor falls in plasma potassium concentrations are probably best avoided in such patients."],"offsets":[[71,1496]]}],"entities":[{"id":"8650","type":"Chemical","text":["potassium"],"offsets":[[11,20]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"8651","type":"Disease","text":["arrhythmias"],"offsets":[[25,36]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"8652","type":"Disease","text":["hypertensive"],"offsets":[[40,52]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"8653","type":"Disease","text":["coronary disease"],"offsets":[[53,69]],"normalized":[{"db_name":"MESH","db_id":"D003327"}]},{"id":"8654","type":"Chemical","text":["potassium"],"offsets":[[122,131]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"8655","type":"Disease","text":["cardiac arrhythmias"],"offsets":[[163,182]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"8656","type":"Disease","text":["coronary artery disease"],"offsets":[[215,238]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"8657","type":"Disease","text":["hypertension"],"offsets":[[358,370]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"8658","type":"Disease","text":["coronary artery disease"],"offsets":[[381,404]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"8659","type":"Chemical","text":["potassium"],"offsets":[[439,448]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"8660","type":"Chemical","text":["amiloride"],"offsets":[[470,479]],"normalized":[{"db_name":"MESH","db_id":"D000584"}]},{"id":"8661","type":"Chemical","text":["potassium"],"offsets":[[507,516]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"8662","type":"Chemical","text":["chlorthalidone"],"offsets":[[534,548]],"normalized":[{"db_name":"MESH","db_id":"D002752"}]},{"id":"8663","type":"Chemical","text":["potassium"],"offsets":[[580,589]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"8664","type":"Chemical","text":["chlorthalidone"],"offsets":[[647,661]],"normalized":[{"db_name":"MESH","db_id":"D002752"}]},{"id":"8665","type":"Chemical","text":["amiloride"],"offsets":[[680,689]],"normalized":[{"db_name":"MESH","db_id":"D000584"}]},{"id":"8666","type":"Chemical","text":["noradrenaline"],"offsets":[[776,789]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"8667","type":"Chemical","text":["norepinephrine"],"offsets":[[791,805]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"8668","type":"Chemical","text":["amiloride"],"offsets":[[866,875]],"normalized":[{"db_name":"MESH","db_id":"D000584"}]},{"id":"8669","type":"Chemical","text":["chlorthalidone"],"offsets":[[891,905]],"normalized":[{"db_name":"MESH","db_id":"D002752"}]},{"id":"8670","type":"Disease","text":["ventricular ectopic beats"],"offsets":[[958,983]],"normalized":[{"db_name":"MESH","db_id":"D018879"}]},{"id":"8671","type":"Chemical","text":["potassium"],"offsets":[[1277,1286]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"8672","type":"Disease","text":["ischaemic heart disease"],"offsets":[[1376,1399]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"8673","type":"Chemical","text":["potassium"],"offsets":[[1428,1437]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]}],"events":[],"coreferences":[],"relations":[{"id":"8674","type":"CID","arg1_id":"8662","arg2_id":"8670","normalized":[]},{"id":"8675","type":"CID","arg1_id":"8664","arg2_id":"8670","normalized":[]},{"id":"8676","type":"CID","arg1_id":"8669","arg2_id":"8670","normalized":[]}]}
{"id":"8677","document_id":"2893236","passages":[{"id":"8678","type":"title","text":["GABA involvement in naloxone induced reversal of respiratory paralysis produced by thiopental."],"offsets":[[0,94]]},{"id":"8679","type":"abstract","text":["No agent is yet available to reverse respiratory paralysis produced by CNS depressants, such as general anesthetics. In this study naloxone reversed respiratory paralysis induced by thiopental in rats. 25 mg\/kg, i.v. thiopental produced anesthesia without altering respiratory rate, increased GABA, decreased glutamate, and had no effect on aspartate or glycine levels compared to controls in rat cortex and brain stem. Pretreatment of rats with thiosemicarbazide for 30 minutes abolished the anesthetic action as well as the respiratory depressant action of thiopental. 50 mg\/kg, i.v. thiopental produced respiratory arrest with further increase in GABA and decrease in glutamate again in cortex and brain stem without affecting any of the amino acids studied in four regions of rat brain. Naloxone (2.5 mg\/kg, i.v.) reversed respiratory paralysis, glutamate and GABA levels to control values in brain stem and cortex with no changes in caudate or cerebellum. These data suggest naloxone reverses respiratory paralysis produced by thiopental and involves GABA in its action."],"offsets":[[95,1170]]}],"entities":[{"id":"8680","type":"Chemical","text":["GABA"],"offsets":[[0,4]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"8681","type":"Chemical","text":["naloxone"],"offsets":[[20,28]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"8682","type":"Disease","text":["respiratory paralysis"],"offsets":[[49,70]],"normalized":[{"db_name":"MESH","db_id":"D012133"}]},{"id":"8683","type":"Chemical","text":["thiopental"],"offsets":[[83,93]],"normalized":[{"db_name":"MESH","db_id":"D013874"}]},{"id":"8684","type":"Disease","text":["respiratory paralysis"],"offsets":[[132,153]],"normalized":[{"db_name":"MESH","db_id":"D012133"}]},{"id":"8685","type":"Chemical","text":["naloxone"],"offsets":[[226,234]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"8686","type":"Disease","text":["respiratory 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arrest"],"offsets":[[701,719]],"normalized":[{"db_name":"MESH","db_id":"D012131"}]},{"id":"8697","type":"Chemical","text":["GABA"],"offsets":[[745,749]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"8698","type":"Chemical","text":["glutamate"],"offsets":[[766,775]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"8699","type":"Chemical","text":["amino acids"],"offsets":[[836,847]],"normalized":[{"db_name":"MESH","db_id":"D000596"}]},{"id":"8700","type":"Chemical","text":["Naloxone"],"offsets":[[886,894]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"8701","type":"Disease","text":["respiratory 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{"id":"8738","document_id":"2533791","passages":[{"id":"8739","type":"title","text":["National project on the prevention of mother-to-infant infection by hepatitis B virus in Japan."],"offsets":[[0,95]]},{"id":"8740","type":"abstract","text":["In Japan, a nationwide prevention program against mother-to-infant infection by hepatitis B virus (HBV) started in 1985. This program consists of double screenings of pregnant women and prophylactic treatment to the infants born to both hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) positive mothers. These infants are treated with two injections of hepatitis B immune globulin (HBIG) and at least three injections of plasma derived hepatitis B vaccine. We sent questionnaires about the numbers of each procedure or examination during nine months of investigation period to each local government in 1986 and 1987. 93.4% pregnant women had the chance to be examined for HBsAg, and the positive rate was 1.4 to 1.5%. The HBeAg positive rate in HBsAg positive was 23 to 26%. The HBsAg positive rate in neonates and in infants before two months were 3% and 2% respectively. Some problems may arise, because 27 to 30% of infants need the fourth vaccination in some restricted areas."],"offsets":[[96,1097]]}],"entities":[{"id":"8741","type":"Disease","text":["infection by hepatitis B virus"],"offsets":[[55,85]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"8742","type":"Disease","text":["infection by hepatitis B virus"],"offsets":[[163,193]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"8743","type":"Chemical","text":["hepatitis B surface antigen"],"offsets":[[333,360]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"8744","type":"Chemical","text":["HBsAg"],"offsets":[[362,367]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"8745","type":"Chemical","text":["hepatitis B e antigen"],"offsets":[[373,394]],"normalized":[{"db_name":"MESH","db_id":"D006513"}]},{"id":"8746","type":"Chemical","text":["HBeAg"],"offsets":[[396,401]],"normalized":[{"db_name":"MESH","db_id":"D006513"}]},{"id":"8747","type":"Disease","text":["hepatitis B"],"offsets":[[470,481]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"8748","type":"Chemical","text":["hepatitis B vaccine"],"offsets":[[553,572]],"normalized":[{"db_name":"MESH","db_id":"D017325"}]},{"id":"8749","type":"Chemical","text":["HBsAg"],"offsets":[[789,794]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"8750","type":"Chemical","text":["HBeAg"],"offsets":[[839,844]],"normalized":[{"db_name":"MESH","db_id":"D006513"}]},{"id":"8751","type":"Chemical","text":["HBsAg"],"offsets":[[862,867]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"8752","type":"Chemical","text":["HBsAg"],"offsets":[[896,901]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]}],"events":[],"coreferences":[],"relations":[{"id":"8753","type":"CID","arg1_id":"8745","arg2_id":"8741","normalized":[]},{"id":"8754","type":"CID","arg1_id":"8745","arg2_id":"8742","normalized":[]},{"id":"8755","type":"CID","arg1_id":"8745","arg2_id":"8747","normalized":[]},{"id":"8756","type":"CID","arg1_id":"8746","arg2_id":"8741","normalized":[]},{"id":"8757","type":"CID","arg1_id":"8746","arg2_id":"8742","normalized":[]},{"id":"8758","type":"CID","arg1_id":"8746","arg2_id":"8747","normalized":[]},{"id":"8759","type":"CID","arg1_id":"8750","arg2_id":"8741","normalized":[]},{"id":"8760","type":"CID","arg1_id":"8750","arg2_id":"8742","normalized":[]},{"id":"8761","type":"CID","arg1_id":"8750","arg2_id":"8747","normalized":[]},{"id":"8762","type":"CID","arg1_id":"8743","arg2_id":"8741","normalized":[]},{"id":"8763","type":"CID","arg1_id":"8743","arg2_id":"8742","normalized":[]},{"id":"8764","type":"CID","arg1_id":"8743","arg2_id":"8747","normalized":[]},{"id":"8765","type":"CID","arg1_id":"8744","arg2_id":"8741","normalized":[]},{"id":"8766","type":"CID","arg1_id":"8744","arg2_id":"8742","normalized":[]},{"id":"8767","type":"CID","arg1_id":"8744","arg2_id":"8747","normalized":[]},{"id":"8768","type":"CID","arg1_id":"8749","arg2_id":"8741","normalized":[]},{"id":"8769","type":"CID","arg1_id":"8749","arg2_id":"8742","normalized":[]},{"id":"8770","type":"CID","arg1_id":"8749","arg2_id":"8747","normalized":[]},{"id":"8771","type":"CID","arg1_id":"8751","arg2_id":"8741","normalized":[]},{"id":"8772","type":"CID","arg1_id":"8751","arg2_id":"8742","normalized":[]},{"id":"8773","type":"CID","arg1_id":"8751","arg2_id":"8747","normalized":[]},{"id":"8774","type":"CID","arg1_id":"8752","arg2_id":"8741","normalized":[]},{"id":"8775","type":"CID","arg1_id":"8752","arg2_id":"8742","normalized":[]},{"id":"8776","type":"CID","arg1_id":"8752","arg2_id":"8747","normalized":[]}]}
{"id":"8777","document_id":"2322844","passages":[{"id":"8778","type":"title","text":["Nociceptive effects induced by intrathecal administration of prostaglandin D2, E2, or F2 alpha to conscious mice."],"offsets":[[0,113]]},{"id":"8779","type":"abstract","text":["The effects of intrathecal administration of prostaglandins on pain responses in conscious mice were evaluated by using hot plate and acetic acid writhing tests. Prostaglandin D2 (0.5-3 ng\/mouse) had a hyperalgesic action on the response to a hot plate during a 3-60 min period after injection. Prostaglandin E2 showed a hyperalgesic effect at doses of 1 pg to 10 ng\/mouse, but the effect lasted shorter (3-30 min) than that of prostaglandin D2. Similar results were obtained by acetic acid writhing tests. The hyperalgesic effect of prostaglandin D2 was blocked by simultaneous injection of a substance P antagonist (greater than or equal to 100 ng) but not by AH6809, a prostanoid EP1-receptor antagonist. Conversely, prostaglandin E2-induced hyperalgesia was blocked by AH6809 (greater than or equal to 500 ng) but not by the substance P antagonist. Prostaglandin F2 alpha had little effect on pain responses. These results demonstrate that both prostaglandin D2 and prostaglandin E2 exert hyperalgesia in the spinal cord, but in different ways."],"offsets":[[114,1162]]}],"entities":[{"id":"8780","type":"Chemical","text":["prostaglandin D2, E2, or F2 alpha"],"offsets":[[61,94]],"normalized":[{"db_name":"MESH","db_id":"D015230"},{"db_name":"MESH","db_id":"D015232"},{"db_name":"MESH","db_id":"D015237"}]},{"id":"8781","type":"Chemical","text":["prostaglandin D2"],"offsets":[[61,77]],"normalized":[{"db_name":"MESH","db_id":"D015230"}]},{"id":"8782","type":"Chemical","text":["prostaglandin","E2"],"offsets":[[61,74],[79,81]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"8783","type":"Chemical","text":["prostaglandin","F2 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E2"],"offsets":[[409,425]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"8790","type":"Disease","text":["hyperalgesic"],"offsets":[[435,447]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"8791","type":"Chemical","text":["pg"],"offsets":[[469,471]],"normalized":[{"db_name":"MESH","db_id":"D011453"}]},{"id":"8792","type":"Chemical","text":["prostaglandin D2"],"offsets":[[542,558]],"normalized":[{"db_name":"MESH","db_id":"D015230"}]},{"id":"8793","type":"Chemical","text":["acetic acid"],"offsets":[[593,604]],"normalized":[{"db_name":"MESH","db_id":"D019342"}]},{"id":"8794","type":"Disease","text":["hyperalgesic"],"offsets":[[625,637]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"8795","type":"Chemical","text":["prostaglandin D2"],"offsets":[[648,664]],"normalized":[{"db_name":"MESH","db_id":"D015230"}]},{"id":"8796","type":"Chemical","text":["AH6809"],"offsets":[[776,782]],"normalized":[{"db_name":"MESH","db_id":"C053876"}]},{"id":"8797","type":"Chemical","text":["prostaglandin E2"],"offsets":[[834,850]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"8798","type":"Disease","text":["hyperalgesia"],"offsets":[[859,871]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"8799","type":"Chemical","text":["AH6809"],"offsets":[[887,893]],"normalized":[{"db_name":"MESH","db_id":"C053876"}]},{"id":"8800","type":"Chemical","text":["Prostaglandin F2 alpha"],"offsets":[[967,989]],"normalized":[{"db_name":"MESH","db_id":"D015237"}]},{"id":"8801","type":"Disease","text":["pain"],"offsets":[[1011,1015]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"8802","type":"Chemical","text":["prostaglandin 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E2"],"offsets":[[1084,1100]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"8804","type":"Disease","text":["hyperalgesia"],"offsets":[[1107,1119]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]}],"events":[],"coreferences":[],"relations":[{"id":"8805","type":"CID","arg1_id":"8780","arg2_id":"8788","normalized":[]},{"id":"8806","type":"CID","arg1_id":"8780","arg2_id":"8790","normalized":[]},{"id":"8807","type":"CID","arg1_id":"8780","arg2_id":"8794","normalized":[]},{"id":"8808","type":"CID","arg1_id":"8780","arg2_id":"8798","normalized":[]},{"id":"8809","type":"CID","arg1_id":"8780","arg2_id":"8804","normalized":[]},{"id":"8810","type":"CID","arg1_id":"8782","arg2_id":"8788","normalized":[]},{"id":"8811","type":"CID","arg1_id":"8782","arg2_id":"8790","normalized":[]},{"id":"8812","type":"CID","arg1_id":"8782","arg2_id":"8794","normalized":[]},{"id":"8813","type":"CID","arg1_id":"8782","arg2_id":"8798","normalized":[]},{"id":"8814","type":"CID","arg1_id":"8782","arg2_id":"8804","normalized":[]},{"id":"8815","type":"CID","arg1_id":"8789","arg2_id":"8788","normalized":[]},{"id":"8816","type":"CID","arg1_id":"8789","arg2_id":"8790","normalized":[]},{"id":"8817","type":"CID","arg1_id":"8789","arg2_id":"8794","normalized":[]},{"id":"8818","type":"CID","arg1_id":"8789","arg2_id":"8798","normalized":[]},{"id":"8819","type":"CID","arg1_id":"8789","arg2_id":"8804","normalized":[]},{"id":"8820","type":"CID","arg1_id":"8797","arg2_id":"8788","normalized":[]},{"id":"8821","type":"CID","arg1_id":"8797","arg2_id":"8790","normalized":[]},{"id":"8822","type":"CID","arg1_id":"8797","arg2_id":"8794","normalized":[]},{"id":"8823","type":"CID","arg1_id":"8797","arg2_id":"8798","normalized":[]},{"id":"8824","type":"CID","arg1_id":"8797","arg2_id":"8804","normalized":[]},{"id":"8825","type":"CID","arg1_id":"8803","arg2_id":"8788","normalized":[]},{"id":"8826","type":"CID","arg1_id":"8803","arg2_id":"8790","normalized":[]},{"id":"8827","type":"CID","arg1_id":"8803","arg2_id":"8794","normalized":[]},{"id":"8828","type":"CID","arg1_id":"8803","arg2_id":"8798","normalized":[]},{"id":"8829","type":"CID","arg1_id":"8803","arg2_id":"8804","normalized":[]},{"id":"8830","type":"CID","arg1_id":"8780","arg2_id":"8788","normalized":[]},{"id":"8831","type":"CID","arg1_id":"8780","arg2_id":"8790","normalized":[]},{"id":"8832","type":"CID","arg1_id":"8780","arg2_id":"8794","normalized":[]},{"id":"8833","type":"CID","arg1_id":"8780","arg2_id":"8798","normalized":[]},{"id":"8834","type":"CID","arg1_id":"8780","arg2_id":"8804","normalized":[]},{"id":"8835","type":"CID","arg1_id":"8781","arg2_id":"8788","normalized":[]},{"id":"8836","type":"CID","arg1_id":"8781","arg2_id":"8790","normalized":[]},{"id":"8837","type":"CID","arg1_id":"8781","arg2_id":"8794","normalized":[]},{"id":"8838","type":"CID","arg1_id":"8781","arg2_id":"8798","normalized":[]},{"id":"8839","type":"CID","arg1_id":"8781","arg2_id":"8804","normalized":[]},{"id":"8840","type":"CID","arg1_id":"8787","arg2_id":"8788","normalized":[]},{"id":"8841","type":"CID","arg1_id":"8787","arg2_id":"8790","normalized":[]},{"id":"8842","type":"CID","arg1_id":"8787","arg2_id":"8794","normalized":[]},{"id":"8843","type":"CID","arg1_id":"8787","arg2_id":"8798","normalized":[]},{"id":"8844","type":"CID","arg1_id":"8787","arg2_id":"8804","normalized":[]},{"id":"8845","type":"CID","arg1_id":"8792","arg2_id":"8788","normalized":[]},{"id":"8846","type":"CID","arg1_id":"8792","arg2_id":"8790","normalized":[]},{"id":"8847","type":"CID","arg1_id":"8792","arg2_id":"8794","normalized":[]},{"id":"8848","type":"CID","arg1_id":"8792","arg2_id":"8798","normalized":[]},{"id":"8849","type":"CID","arg1_id":"8792","arg2_id":"8804","normalized":[]},{"id":"8850","type":"CID","arg1_id":"8795","arg2_id":"8788","normalized":[]},{"id":"8851","type":"CID","arg1_id":"8795","arg2_id":"8790","normalized":[]},{"id":"8852","type":"CID","arg1_id":"8795","arg2_id":"8794","normalized":[]},{"id":"8853","type":"CID","arg1_id":"8795","arg2_id":"8798","normalized":[]},{"id":"8854","type":"CID","arg1_id":"8795","arg2_id":"8804","normalized":[]},{"id":"8855","type":"CID","arg1_id":"8802","arg2_id":"8788","normalized":[]},{"id":"8856","type":"CID","arg1_id":"8802","arg2_id":"8790","normalized":[]},{"id":"8857","type":"CID","arg1_id":"8802","arg2_id":"8794","normalized":[]},{"id":"8858","type":"CID","arg1_id":"8802","arg2_id":"8798","normalized":[]},{"id":"8859","type":"CID","arg1_id":"8802","arg2_id":"8804","normalized":[]}]}
{"id":"8860","document_id":"20552622","passages":[{"id":"8861","type":"title","text":["Swallowing-induced atrial tachyarrhythmia triggered by salbutamol: case report and review of the literature."],"offsets":[[0,108]]},{"id":"8862","type":"abstract","text":["CASE: A 49-year-old patient experienced chest discomfort while swallowing. On electrocardiogram, episodes of atrial tachyarrhythmia were recorded immediately after swallowing; 24-hour Holter monitoring recorded several events. The arrhythmia resolved after therapy with atenolol, but recurred a year later. The patient noticed that before these episodes he had been using an inhalator of salbutamol. After stopping the beta-agonist, and after a week with the atenolol, the arrhythmia disappeared. DISCUSSION: Swallowing-induced atrial tachyarrhythmia (SIAT) is a rare phenomenon. Fewer than 50 cases of SIAT have been described in the literature. This article summarizes all the cases published, creating a comprehensive review of the current knowledge and approach to SIAT. It discusses demographics, clinical characteristics and types of arrhythmia, postulated mechanisms of SIAT, and different treatment possibilities such as medications, surgery, and radiofrequency catheter ablation (RFCA). CONCLUSION: Salbutamol is presented here as a possible trigger for SIAT. Although it is difficult to define causality in a case report, it is logical to think that a beta-agonist like salbutamol (known to induce tachycardia) may be the trigger of adrenergic reflexes originating in the esophagus while swallowing and that a beta-blocker such as atenolol (that blocks the adrenergic activity) may relieve it."],"offsets":[[109,1512]]}],"entities":[{"id":"8863","type":"Disease","text":["atrial tachyarrhythmia"],"offsets":[[19,41]],"normalized":[{"db_name":"MESH","db_id":"D013617"}]},{"id":"8864","type":"Chemical","text":["salbutamol"],"offsets":[[55,65]],"normalized":[{"db_name":"MESH","db_id":"D000420"}]},{"id":"8865","type":"Disease","text":["atrial tachyarrhythmia"],"offsets":[[218,240]],"normalized":[{"db_name":"MESH","db_id":"D013617"}]},{"id":"8866","type":"Disease","text":["arrhythmia"],"offsets":[[340,350]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"8867","type":"Chemical","text":["atenolol"],"offsets":[[379,387]],"normalized":[{"db_name":"MESH","db_id":"D001262"}]},{"id":"8868","type":"Chemical","text":["salbutamol"],"offsets":[[497,507]],"normalized":[{"db_name":"MESH","db_id":"D000420"}]},{"id":"8869","type":"Chemical","text":["atenolol"],"offsets":[[568,576]],"normalized":[{"db_name":"MESH","db_id":"D001262"}]},{"id":"8870","type":"Disease","text":["arrhythmia"],"offsets":[[582,592]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"8871","type":"Disease","text":["atrial 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{"id":"8914","document_id":"20510337","passages":[{"id":"8915","type":"title","text":["Coenzyme Q10 treatment ameliorates acute cisplatin nephrotoxicity in mice."],"offsets":[[0,74]]},{"id":"8916","type":"abstract","text":["The nephroprotective effect of coenzyme Q10 was investigated in mice with acute renal injury induced by a single i.p. injection of cisplatin (5 mg\/kg). Coenzyme Q10 treatment (10 mg\/kg\/day, i.p.) was applied for 6 consecutive days, starting 1 day before cisplatin administration. Coenzyme Q10 significantly reduced blood urea nitrogen and serum creatinine levels which were increased by cisplatin. Coenzyme Q10 significantly compensated deficits in the antioxidant defense mechanisms (reduced glutathione level and superoxide dismutase activity), suppressed lipid peroxidation, decreased the elevations of tumor necrosis factor-alpha, nitric oxide and platinum ion concentration, and attenuated the reductions of selenium and zinc ions in renal tissue resulted from cisplatin administration. Also, histopathological renal tissue damage mediated by cisplatin was ameliorated by coenzyme Q10 treatment. Immunohistochemical analysis revealed that coenzyme Q10 significantly decreased the cisplatin-induced overexpression of inducible nitric oxide synthase, nuclear factor-kappaB, caspase-3 and p53 in renal tissue. It was concluded that coenzyme Q10 represents a potential therapeutic option to protect against acute cisplatin nephrotoxicity commonly encountered in clinical practice."],"offsets":[[75,1356]]}],"entities":[{"id":"8917","type":"Chemical","text":["Coenzyme Q10"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"C024989"}]},{"id":"8918","type":"Chemical","text":["cisplatin"],"offsets":[[41,50]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"8919","type":"Disease","text":["nephrotoxicity"],"offsets":[[51,65]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"8920","type":"Chemical","text":["coenzyme Q10"],"offsets":[[106,118]],"normalized":[{"db_name":"MESH","db_id":"C024989"}]},{"id":"8921","type":"Disease","text":["acute renal injury"],"offsets":[[149,167]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"8922","type":"Chemical","text":["cisplatin"],"offsets":[[206,215]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"8923","type":"Chemical","text":["Coenzyme Q10"],"offsets":[[227,239]],"normalized":[{"db_name":"MESH","db_id":"C024989"}]},{"id":"8924","type":"Chemical","text":["cisplatin"],"offsets":[[329,338]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"8925","type":"Chemical","text":["Coenzyme Q10"],"offsets":[[355,367]],"normalized":[{"db_name":"MESH","db_id":"C024989"}]},{"id":"8926","type":"Chemical","text":["blood urea nitrogen"],"offsets":[[390,409]],"normalized":[{"db_name":"MESH","db_id":"D001806"}]},{"id":"8927","type":"Chemical","text":["creatinine"],"offsets":[[420,430]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"8928","type":"Chemical","text":["cisplatin"],"offsets":[[462,471]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"8929","type":"Chemical","text":["Coenzyme Q10"],"offsets":[[473,485]],"normalized":[{"db_name":"MESH","db_id":"C024989"}]},{"id":"8930","type":"Chemical","text":["reduced glutathione"],"offsets":[[560,579]],"normalized":[{"db_name":"MESH","db_id":"D005978"}]},{"id":"8931","type":"Chemical","text":["superoxide"],"offsets":[[590,600]],"normalized":[{"db_name":"MESH","db_id":"D013481"}]},{"id":"8932","type":"Disease","text":["tumor"],"offsets":[[681,686]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"8933","type":"Disease","text":["necrosis"],"offsets":[[687,695]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"8934","type":"Chemical","text":["nitric oxide"],"offsets":[[710,722]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"8935","type":"Chemical","text":["platinum"],"offsets":[[727,735]],"normalized":[{"db_name":"MESH","db_id":"D010984"}]},{"id":"8936","type":"Chemical","text":["selenium"],"offsets":[[788,796]],"normalized":[{"db_name":"MESH","db_id":"D012643"}]},{"id":"8937","type":"Chemical","text":["zinc"],"offsets":[[801,805]],"normalized":[{"db_name":"MESH","db_id":"D015032"}]},{"id":"8938","type":"Chemical","text":["cisplatin"],"offsets":[[841,850]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"8939","type":"Disease","text":["renal tissue damage"],"offsets":[[891,910]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"8940","type":"Chemical","text":["cisplatin"],"offsets":[[923,932]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"8941","type":"Chemical","text":["coenzyme Q10"],"offsets":[[952,964]],"normalized":[{"db_name":"MESH","db_id":"C024989"}]},{"id":"8942","type":"Chemical","text":["coenzyme Q10"],"offsets":[[1019,1031]],"normalized":[{"db_name":"MESH","db_id":"C024989"}]},{"id":"8943","type":"Chemical","text":["cisplatin"],"offsets":[[1060,1069]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"8944","type":"Chemical","text":["nitric oxide"],"offsets":[[1106,1118]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"8945","type":"Chemical","text":["coenzyme Q10"],"offsets":[[1209,1221]],"normalized":[{"db_name":"MESH","db_id":"C024989"}]},{"id":"8946","type":"Chemical","text":["cisplatin"],"offsets":[[1289,1298]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"8947","type":"Disease","text":["nephrotoxicity"],"offsets":[[1299,1313]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"8948","type":"CID","arg1_id":"8918","arg2_id":"8921","normalized":[]},{"id":"8949","type":"CID","arg1_id":"8922","arg2_id":"8921","normalized":[]},{"id":"8950","type":"CID","arg1_id":"8924","arg2_id":"8921","normalized":[]},{"id":"8951","type":"CID","arg1_id":"8928","arg2_id":"8921","normalized":[]},{"id":"8952","type":"CID","arg1_id":"8938","arg2_id":"8921","normalized":[]},{"id":"8953","type":"CID","arg1_id":"8940","arg2_id":"8921","normalized":[]},{"id":"8954","type":"CID","arg1_id":"8943","arg2_id":"8921","normalized":[]},{"id":"8955","type":"CID","arg1_id":"8946","arg2_id":"8921","normalized":[]}]}
{"id":"8956","document_id":"20164825","passages":[{"id":"8957","type":"title","text":["Metformin prevents experimental gentamicin-induced nephropathy by a mitochondria-dependent pathway."],"offsets":[[0,99]]},{"id":"8958","type":"abstract","text":["The antidiabetic drug metformin can diminish apoptosis induced by oxidative stress in endothelial cells and prevent vascular dysfunction even in nondiabetic patients. Here we tested whether it has a beneficial effect in a rat model of gentamicin toxicity. Mitochondrial analysis, respiration intensity, levels of reactive oxygen species, permeability transition, and cytochrome c release were assessed 3 and 6 days after gentamicin administration. Metformin treatment fully blocked gentamicin-mediated acute renal failure. This was accompanied by a lower activity of N-acetyl-beta-D-glucosaminidase, together with a decrease of lipid peroxidation and increase of antioxidant systems. Metformin also protected the kidney from histological damage 6 days after gentamicin administration. These in vivo markers of kidney dysfunction and their correction by metformin were complemented by in vitro studies of mitochondrial function. We found that gentamicin treatment depleted respiratory components (cytochrome c, NADH), probably due to the opening of mitochondrial transition pores. These injuries, partly mediated by a rise in reactive oxygen species from the electron transfer chain, were significantly decreased by metformin. Thus, our study suggests that pleiotropic effects of metformin can lessen gentamicin nephrotoxicity and improve mitochondrial homeostasis."],"offsets":[[100,1464]]}],"entities":[{"id":"8959","type":"Chemical","text":["Metformin"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D008687"}]},{"id":"8960","type":"Chemical","text":["gentamicin"],"offsets":[[32,42]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"8961","type":"Disease","text":["nephropathy"],"offsets":[[51,62]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"8962","type":"Chemical","text":["metformin"],"offsets":[[122,131]],"normalized":[{"db_name":"MESH","db_id":"D008687"}]},{"id":"8963","type":"Disease","text":["vascular dysfunction"],"offsets":[[216,236]],"normalized":[{"db_name":"MESH","db_id":"D014652"}]},{"id":"8964","type":"Chemical","text":["gentamicin"],"offsets":[[335,345]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"8965","type":"Disease","text":["toxicity"],"offsets":[[346,354]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"8966","type":"Chemical","text":["oxygen"],"offsets":[[422,428]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"8967","type":"Chemical","text":["gentamicin"],"offsets":[[521,531]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"8968","type":"Chemical","text":["Metformin"],"offsets":[[548,557]],"normalized":[{"db_name":"MESH","db_id":"D008687"}]},{"id":"8969","type":"Chemical","text":["gentamicin"],"offsets":[[582,592]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"8970","type":"Disease","text":["acute renal failure"],"offsets":[[602,621]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"8971","type":"Chemical","text":["Metformin"],"offsets":[[784,793]],"normalized":[{"db_name":"MESH","db_id":"D008687"}]},{"id":"8972","type":"Chemical","text":["gentamicin"],"offsets":[[858,868]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"8973","type":"Disease","text":["kidney dysfunction"],"offsets":[[910,928]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"8974","type":"Chemical","text":["metformin"],"offsets":[[953,962]],"normalized":[{"db_name":"MESH","db_id":"D008687"}]},{"id":"8975","type":"Chemical","text":["gentamicin"],"offsets":[[1042,1052]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"8976","type":"Chemical","text":["oxygen"],"offsets":[[1234,1240]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"8977","type":"Chemical","text":["metformin"],"offsets":[[1315,1324]],"normalized":[{"db_name":"MESH","db_id":"D008687"}]},{"id":"8978","type":"Chemical","text":["metformin"],"offsets":[[1379,1388]],"normalized":[{"db_name":"MESH","db_id":"D008687"}]},{"id":"8979","type":"Chemical","text":["gentamicin"],"offsets":[[1400,1410]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"8980","type":"Disease","text":["nephrotoxicity"],"offsets":[[1411,1425]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"8981","type":"CID","arg1_id":"8960","arg2_id":"8970","normalized":[]},{"id":"8982","type":"CID","arg1_id":"8964","arg2_id":"8970","normalized":[]},{"id":"8983","type":"CID","arg1_id":"8967","arg2_id":"8970","normalized":[]},{"id":"8984","type":"CID","arg1_id":"8969","arg2_id":"8970","normalized":[]},{"id":"8985","type":"CID","arg1_id":"8972","arg2_id":"8970","normalized":[]},{"id":"8986","type":"CID","arg1_id":"8975","arg2_id":"8970","normalized":[]},{"id":"8987","type":"CID","arg1_id":"8979","arg2_id":"8970","normalized":[]}]}
{"id":"8988","document_id":"20042557","passages":[{"id":"8989","type":"title","text":["Sedation depth during spinal anesthesia and the development of postoperative delirium in elderly patients undergoing hip fracture repair."],"offsets":[[0,137]]},{"id":"8990","type":"abstract","text":["OBJECTIVE: To determine whether limiting intraoperative sedation depth during spinal anesthesia for hip fracture repair in elderly patients can decrease the prevalence of postoperative delirium. PATIENTS AND METHODS: We performed a double-blind, randomized controlled trial at an academic medical center of elderly patients (>or=65 years) without preoperative delirium or severe dementia who underwent hip fracture repair under spinal anesthesia with propofol sedation. Sedation depth was titrated using processed electroencephalography with the bispectral index (BIS), and patients were randomized to receive either deep (BIS, approximately 50) or light (BIS, >or=80) sedation. Postoperative delirium was assessed as defined by Diagnostic and Statistical Manual of Mental Disorders (Third Edition Revised) criteria using the Confusion Assessment Method beginning at any time from the second day after surgery. RESULTS: From April 2, 2005, through October 30, 2008, a total of 114 patients were randomized. The prevalence of postoperative delirium was significantly lower in the light sedation group (11\/57 [19%] vs 23\/57 [40%] in the deep sedation group; P=.02), indicating that 1 incident of delirium will be prevented for every 4.7 patients treated with light sedation. The mean +\/- SD number of days of delirium during hospitalization was lower in the light sedation group than in the deep sedation group (0.5+\/-1.5 days vs 1.4+\/-4.0 days; P=.01). CONCLUSION: The use of light propofol sedation decreased the prevalence of postoperative delirium by 50% compared with deep sedation. Limiting depth of sedation during spinal anesthesia is a simple, safe, and cost-effective intervention for preventing postoperative delirium in elderly patients that could be widely and readily adopted."],"offsets":[[138,1926]]}],"entities":[{"id":"8991","type":"Disease","text":["postoperative delirium"],"offsets":[[63,85]],"normalized":[{"db_name":"MESH","db_id":"D011183"},{"db_name":"MESH","db_id":"D003693"}]},{"id":"8992","type":"Disease","text":["postoperative delirium"],"offsets":[[63,85]],"normalized":[{"db_name":"MESH","db_id":"D011183"}]},{"id":"8993","type":"Disease","text":["delirium"],"offsets":[[77,85]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"8994","type":"Disease","text":["hip fracture"],"offsets":[[117,129]],"normalized":[{"db_name":"MESH","db_id":"D006620"}]},{"id":"8995","type":"Disease","text":["hip fracture"],"offsets":[[238,250]],"normalized":[{"db_name":"MESH","db_id":"D006620"}]},{"id":"8996","type":"Disease","text":["postoperative delirium"],"offsets":[[309,331]],"normalized":[{"db_name":"MESH","db_id":"D011183"},{"db_name":"MESH","db_id":"D003693"}]},{"id":"8997","type":"Disease","text":["postoperative delirium"],"offsets":[[309,331]],"normalized":[{"db_name":"MESH","db_id":"D011183"}]},{"id":"8998","type":"Disease","text":["delirium"],"offsets":[[323,331]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"8999","type":"Disease","text":["delirium"],"offsets":[[498,506]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"9000","type":"Disease","text":["dementia"],"offsets":[[517,525]],"normalized":[{"db_name":"MESH","db_id":"D003704"}]},{"id":"9001","type":"Disease","text":["hip fracture"],"offsets":[[540,552]],"normalized":[{"db_name":"MESH","db_id":"D006620"}]},{"id":"9002","type":"Chemical","text":["propofol"],"offsets":[[589,597]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"9003","type":"Disease","text":["Postoperative delirium"],"offsets":[[817,839]],"normalized":[{"db_name":"MESH","db_id":"D011183"},{"db_name":"MESH","db_id":"D003693"}]},{"id":"9004","type":"Disease","text":["Postoperative delirium"],"offsets":[[817,839]],"normalized":[{"db_name":"MESH","db_id":"D011183"}]},{"id":"9005","type":"Disease","text":["delirium"],"offsets":[[831,839]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"9006","type":"Disease","text":["Mental Disorders"],"offsets":[[904,920]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"9007","type":"Disease","text":["postoperative delirium"],"offsets":[[1163,1185]],"normalized":[{"db_name":"MESH","db_id":"D011183"},{"db_name":"MESH","db_id":"D003693"}]},{"id":"9008","type":"Disease","text":["postoperative delirium"],"offsets":[[1163,1185]],"normalized":[{"db_name":"MESH","db_id":"D011183"}]},{"id":"9009","type":"Disease","text":["delirium"],"offsets":[[1177,1185]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"9010","type":"Disease","text":["delirium"],"offsets":[[1332,1340]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"9011","type":"Disease","text":["delirium"],"offsets":[[1445,1453]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"9012","type":"Chemical","text":["propofol"],"offsets":[[1619,1627]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"9013","type":"Disease","text":["postoperative delirium"],"offsets":[[1665,1687]],"normalized":[{"db_name":"MESH","db_id":"D011183"},{"db_name":"MESH","db_id":"D003693"}]},{"id":"9014","type":"Disease","text":["postoperative delirium"],"offsets":[[1665,1687]],"normalized":[{"db_name":"MESH","db_id":"D011183"}]},{"id":"9015","type":"Disease","text":["delirium"],"offsets":[[1679,1687]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"9016","type":"Disease","text":["postoperative delirium"],"offsets":[[1842,1864]],"normalized":[{"db_name":"MESH","db_id":"D011183"},{"db_name":"MESH","db_id":"D003693"}]},{"id":"9017","type":"Disease","text":["postoperative delirium"],"offsets":[[1842,1864]],"normalized":[{"db_name":"MESH","db_id":"D011183"}]},{"id":"9018","type":"Disease","text":["delirium"],"offsets":[[1856,1864]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]}],"events":[],"coreferences":[],"relations":[{"id":"9019","type":"CID","arg1_id":"9002","arg2_id":"8991","normalized":[]},{"id":"9020","type":"CID","arg1_id":"9002","arg2_id":"8993","normalized":[]},{"id":"9021","type":"CID","arg1_id":"9002","arg2_id":"8996","normalized":[]},{"id":"9022","type":"CID","arg1_id":"9002","arg2_id":"8998","normalized":[]},{"id":"9023","type":"CID","arg1_id":"9002","arg2_id":"8999","normalized":[]},{"id":"9024","type":"CID","arg1_id":"9002","arg2_id":"9003","normalized":[]},{"id":"9025","type":"CID","arg1_id":"9002","arg2_id":"9005","normalized":[]},{"id":"9026","type":"CID","arg1_id":"9002","arg2_id":"9007","normalized":[]},{"id":"9027","type":"CID","arg1_id":"9002","arg2_id":"9009","normalized":[]},{"id":"9028","type":"CID","arg1_id":"9002","arg2_id":"9010","normalized":[]},{"id":"9029","type":"CID","arg1_id":"9002","arg2_id":"9011","normalized":[]},{"id":"9030","type":"CID","arg1_id":"9002","arg2_id":"9013","normalized":[]},{"id":"9031","type":"CID","arg1_id":"9002","arg2_id":"9015","normalized":[]},{"id":"9032","type":"CID","arg1_id":"9002","arg2_id":"9016","normalized":[]},{"id":"9033","type":"CID","arg1_id":"9002","arg2_id":"9018","normalized":[]},{"id":"9034","type":"CID","arg1_id":"9012","arg2_id":"8991","normalized":[]},{"id":"9035","type":"CID","arg1_id":"9012","arg2_id":"8993","normalized":[]},{"id":"9036","type":"CID","arg1_id":"9012","arg2_id":"8996","normalized":[]},{"id":"9037","type":"CID","arg1_id":"9012","arg2_id":"8998","normalized":[]},{"id":"9038","type":"CID","arg1_id":"9012","arg2_id":"8999","normalized":[]},{"id":"9039","type":"CID","arg1_id":"9012","arg2_id":"9003","normalized":[]},{"id":"9040","type":"CID","arg1_id":"9012","arg2_id":"9005","normalized":[]},{"id":"9041","type":"CID","arg1_id":"9012","arg2_id":"9007","normalized":[]},{"id":"9042","type":"CID","arg1_id":"9012","arg2_id":"9009","normalized":[]},{"id":"9043","type":"CID","arg1_id":"9012","arg2_id":"9010","normalized":[]},{"id":"9044","type":"CID","arg1_id":"9012","arg2_id":"9011","normalized":[]},{"id":"9045","type":"CID","arg1_id":"9012","arg2_id":"9013","normalized":[]},{"id":"9046","type":"CID","arg1_id":"9012","arg2_id":"9015","normalized":[]},{"id":"9047","type":"CID","arg1_id":"9012","arg2_id":"9016","normalized":[]},{"id":"9048","type":"CID","arg1_id":"9012","arg2_id":"9018","normalized":[]},{"id":"9049","type":"CID","arg1_id":"9002","arg2_id":"8991","normalized":[]},{"id":"9050","type":"CID","arg1_id":"9002","arg2_id":"8992","normalized":[]},{"id":"9051","type":"CID","arg1_id":"9002","arg2_id":"8996","normalized":[]},{"id":"9052","type":"CID","arg1_id":"9002","arg2_id":"8997","normalized":[]},{"id":"9053","type":"CID","arg1_id":"9002","arg2_id":"9003","normalized":[]},{"id":"9054","type":"CID","arg1_id":"9002","arg2_id":"9004","normalized":[]},{"id":"9055","type":"CID","arg1_id":"9002","arg2_id":"9007","normalized":[]},{"id":"9056","type":"CID","arg1_id":"9002","arg2_id":"9008","normalized":[]},{"id":"9057","type":"CID","arg1_id":"9002","arg2_id":"9013","normalized":[]},{"id":"9058","type":"CID","arg1_id":"9002","arg2_id":"9014","normalized":[]},{"id":"9059","type":"CID","arg1_id":"9002","arg2_id":"9016","normalized":[]},{"id":"9060","type":"CID","arg1_id":"9002","arg2_id":"9017","normalized":[]},{"id":"9061","type":"CID","arg1_id":"9012","arg2_id":"8991","normalized":[]},{"id":"9062","type":"CID","arg1_id":"9012","arg2_id":"8992","normalized":[]},{"id":"9063","type":"CID","arg1_id":"9012","arg2_id":"8996","normalized":[]},{"id":"9064","type":"CID","arg1_id":"9012","arg2_id":"8997","normalized":[]},{"id":"9065","type":"CID","arg1_id":"9012","arg2_id":"9003","normalized":[]},{"id":"9066","type":"CID","arg1_id":"9012","arg2_id":"9004","normalized":[]},{"id":"9067","type":"CID","arg1_id":"9012","arg2_id":"9007","normalized":[]},{"id":"9068","type":"CID","arg1_id":"9012","arg2_id":"9008","normalized":[]},{"id":"9069","type":"CID","arg1_id":"9012","arg2_id":"9013","normalized":[]},{"id":"9070","type":"CID","arg1_id":"9012","arg2_id":"9014","normalized":[]},{"id":"9071","type":"CID","arg1_id":"9012","arg2_id":"9016","normalized":[]},{"id":"9072","type":"CID","arg1_id":"9012","arg2_id":"9017","normalized":[]}]}
{"id":"9073","document_id":"19944333","passages":[{"id":"9074","type":"title","text":["Sorafenib-induced acute myocardial infarction due to coronary artery spasm."],"offsets":[[0,75]]},{"id":"9075","type":"abstract","text":["A 65-year-old man with advanced renal cell carcinoma was admitted due to continuing chest pain at rest. Two weeks before his admission, sorafenib had been started. He was diagnosed with non-ST-elevation myocardial infarction by laboratory data and electrocardiogram. Enhanced heart magnetic resonance imaging also showed subendocardial infarction. However, there was no stenosis in coronary arteries on angiography. Coronary artery spasm was induced by a provocative test. Cessation of sorafenib and administration of Ca-channel blocker and nitrates ameliorated his symptoms, but relapse occurred after resumption of sorafenib. Addition of oral nicorandil reduced his symptoms and maintained stable angina status. We report the first case of sorafenib-induced coronary artery spasm. Sorafenib is a multikinase inhibitor that targets signaling pathways necessary for cellular proliferation and survival. On the other hand, the Rho\/ROCK pathway has an important role in the pathogenesis of coronary artery spasm. Our report may show an adverse effect on the Rho\/ROCK pathway by sorafenib use."],"offsets":[[76,1166]]}],"entities":[{"id":"9076","type":"Chemical","text":["Sorafenib"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"C471405"}]},{"id":"9077","type":"Disease","text":["myocardial infarction"],"offsets":[[24,45]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"9078","type":"Disease","text":["coronary artery spasm"],"offsets":[[53,74]],"normalized":[{"db_name":"MESH","db_id":"D003329"}]},{"id":"9079","type":"Disease","text":["renal cell carcinoma"],"offsets":[[108,128]],"normalized":[{"db_name":"MESH","db_id":"D002292"}]},{"id":"9080","type":"Disease","text":["chest pain"],"offsets":[[160,170]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"9081","type":"Chemical","text":["sorafenib"],"offsets":[[212,221]],"normalized":[{"db_name":"MESH","db_id":"C471405"}]},{"id":"9082","type":"Disease","text":["myocardial infarction"],"offsets":[[279,300]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"9083","type":"Disease","text":["subendocardial infarction"],"offsets":[[397,422]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"9084","type":"Disease","text":["Coronary artery spasm"],"offsets":[[492,513]],"normalized":[{"db_name":"MESH","db_id":"D003329"}]},{"id":"9085","type":"Chemical","text":["sorafenib"],"offsets":[[562,571]],"normalized":[{"db_name":"MESH","db_id":"C471405"}]},{"id":"9086","type":"Chemical","text":["Ca"],"offsets":[[594,596]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"9087","type":"Chemical","text":["nitrates"],"offsets":[[617,625]],"normalized":[{"db_name":"MESH","db_id":"D009566"}]},{"id":"9088","type":"Chemical","text":["sorafenib"],"offsets":[[693,702]],"normalized":[{"db_name":"MESH","db_id":"C471405"}]},{"id":"9089","type":"Chemical","text":["nicorandil"],"offsets":[[721,731]],"normalized":[{"db_name":"MESH","db_id":"D020108"}]},{"id":"9090","type":"Disease","text":["stable angina"],"offsets":[[768,781]],"normalized":[{"db_name":"MESH","db_id":"D060050"}]},{"id":"9091","type":"Chemical","text":["sorafenib"],"offsets":[[818,827]],"normalized":[{"db_name":"MESH","db_id":"C471405"}]},{"id":"9092","type":"Disease","text":["coronary artery spasm"],"offsets":[[836,857]],"normalized":[{"db_name":"MESH","db_id":"D003329"}]},{"id":"9093","type":"Chemical","text":["Sorafenib"],"offsets":[[859,868]],"normalized":[{"db_name":"MESH","db_id":"C471405"}]},{"id":"9094","type":"Disease","text":["coronary artery spasm"],"offsets":[[1064,1085]],"normalized":[{"db_name":"MESH","db_id":"D003329"}]},{"id":"9095","type":"Chemical","text":["sorafenib"],"offsets":[[1152,1161]],"normalized":[{"db_name":"MESH","db_id":"C471405"}]}],"events":[],"coreferences":[],"relations":[{"id":"9096","type":"CID","arg1_id":"9076","arg2_id":"9078","normalized":[]},{"id":"9097","type":"CID","arg1_id":"9076","arg2_id":"9084","normalized":[]},{"id":"9098","type":"CID","arg1_id":"9076","arg2_id":"9092","normalized":[]},{"id":"9099","type":"CID","arg1_id":"9076","arg2_id":"9094","normalized":[]},{"id":"9100","type":"CID","arg1_id":"9081","arg2_id":"9078","normalized":[]},{"id":"9101","type":"CID","arg1_id":"9081","arg2_id":"9084","normalized":[]},{"id":"9102","type":"CID","arg1_id":"9081","arg2_id":"9092","normalized":[]},{"id":"9103","type":"CID","arg1_id":"9081","arg2_id":"9094","normalized":[]},{"id":"9104","type":"CID","arg1_id":"9085","arg2_id":"9078","normalized":[]},{"id":"9105","type":"CID","arg1_id":"9085","arg2_id":"9084","normalized":[]},{"id":"9106","type":"CID","arg1_id":"9085","arg2_id":"9092","normalized":[]},{"id":"9107","type":"CID","arg1_id":"9085","arg2_id":"9094","normalized":[]},{"id":"9108","type":"CID","arg1_id":"9088","arg2_id":"9078","normalized":[]},{"id":"9109","type":"CID","arg1_id":"9088","arg2_id":"9084","normalized":[]},{"id":"9110","type":"CID","arg1_id":"9088","arg2_id":"9092","normalized":[]},{"id":"9111","type":"CID","arg1_id":"9088","arg2_id":"9094","normalized":[]},{"id":"9112","type":"CID","arg1_id":"9091","arg2_id":"9078","normalized":[]},{"id":"9113","type":"CID","arg1_id":"9091","arg2_id":"9084","normalized":[]},{"id":"9114","type":"CID","arg1_id":"9091","arg2_id":"9092","normalized":[]},{"id":"9115","type":"CID","arg1_id":"9091","arg2_id":"9094","normalized":[]},{"id":"9116","type":"CID","arg1_id":"9093","arg2_id":"9078","normalized":[]},{"id":"9117","type":"CID","arg1_id":"9093","arg2_id":"9084","normalized":[]},{"id":"9118","type":"CID","arg1_id":"9093","arg2_id":"9092","normalized":[]},{"id":"9119","type":"CID","arg1_id":"9093","arg2_id":"9094","normalized":[]},{"id":"9120","type":"CID","arg1_id":"9095","arg2_id":"9078","normalized":[]},{"id":"9121","type":"CID","arg1_id":"9095","arg2_id":"9084","normalized":[]},{"id":"9122","type":"CID","arg1_id":"9095","arg2_id":"9092","normalized":[]},{"id":"9123","type":"CID","arg1_id":"9095","arg2_id":"9094","normalized":[]}]}
{"id":"9124","document_id":"17975693","passages":[{"id":"9125","type":"title","text":["Anxiogenic potential of ciprofloxacin and norfloxacin in rats."],"offsets":[[0,62]]},{"id":"9126","type":"abstract","text":["INTRODUCTION: The possible anxiogenic effects of fluoroquinolones, namely ciprofloxacin and norfloxacin, were investigated in adult Charles Foster albino rats of either sex, weighing 150-200 g. METHODS: The drugs were given orally, in doses of 50 mg\/kg for five consecutive days and the experiments were performed on the fifth day. The tests included open-field exploratory behaviour, elevated plus maze and elevated zero maze, social interaction and novelty-suppressed feeding latency behaviour. RESULTS: The results indicate that ciprofloxacin- and norfloxacin-treated rats showed anxious behaviour in comparison to control rats in all the parameters studied. However, ciprofloxacin- and norfloxacin-treated rats did not differ significantly from each other in various behavioural parameters. CONCLUSION: The present experimental findings substantiate the clinically observed anxiogenic potential of ciprofloxacin and norfloxacin."],"offsets":[[63,995]]}],"entities":[{"id":"9127","type":"Chemical","text":["ciprofloxacin"],"offsets":[[24,37]],"normalized":[{"db_name":"MESH","db_id":"D002939"}]},{"id":"9128","type":"Chemical","text":["norfloxacin"],"offsets":[[42,53]],"normalized":[{"db_name":"MESH","db_id":"D009643"}]},{"id":"9129","type":"Chemical","text":["fluoroquinolones"],"offsets":[[112,128]],"normalized":[{"db_name":"MESH","db_id":"D024841"}]},{"id":"9130","type":"Chemical","text":["ciprofloxacin"],"offsets":[[137,150]],"normalized":[{"db_name":"MESH","db_id":"D002939"}]},{"id":"9131","type":"Chemical","text":["norfloxacin"],"offsets":[[155,166]],"normalized":[{"db_name":"MESH","db_id":"D009643"}]},{"id":"9132","type":"Chemical","text":["ciprofloxacin"],"offsets":[[595,608]],"normalized":[{"db_name":"MESH","db_id":"D002939"}]},{"id":"9133","type":"Chemical","text":["norfloxacin"],"offsets":[[614,625]],"normalized":[{"db_name":"MESH","db_id":"D009643"}]},{"id":"9134","type":"Disease","text":["anxious behaviour"],"offsets":[[646,663]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"9135","type":"Chemical","text":["ciprofloxacin"],"offsets":[[734,747]],"normalized":[{"db_name":"MESH","db_id":"D002939"}]},{"id":"9136","type":"Chemical","text":["norfloxacin"],"offsets":[[753,764]],"normalized":[{"db_name":"MESH","db_id":"D009643"}]},{"id":"9137","type":"Chemical","text":["ciprofloxacin"],"offsets":[[965,978]],"normalized":[{"db_name":"MESH","db_id":"D002939"}]},{"id":"9138","type":"Chemical","text":["norfloxacin"],"offsets":[[983,994]],"normalized":[{"db_name":"MESH","db_id":"D009643"}]}],"events":[],"coreferences":[],"relations":[{"id":"9139","type":"CID","arg1_id":"9128","arg2_id":"9134","normalized":[]},{"id":"9140","type":"CID","arg1_id":"9131","arg2_id":"9134","normalized":[]},{"id":"9141","type":"CID","arg1_id":"9133","arg2_id":"9134","normalized":[]},{"id":"9142","type":"CID","arg1_id":"9136","arg2_id":"9134","normalized":[]},{"id":"9143","type":"CID","arg1_id":"9138","arg2_id":"9134","normalized":[]},{"id":"9144","type":"CID","arg1_id":"9127","arg2_id":"9134","normalized":[]},{"id":"9145","type":"CID","arg1_id":"9130","arg2_id":"9134","normalized":[]},{"id":"9146","type":"CID","arg1_id":"9132","arg2_id":"9134","normalized":[]},{"id":"9147","type":"CID","arg1_id":"9135","arg2_id":"9134","normalized":[]},{"id":"9148","type":"CID","arg1_id":"9137","arg2_id":"9134","normalized":[]}]}
{"id":"9149","document_id":"17943461","passages":[{"id":"9150","type":"title","text":["Myocardial Fas ligand expression increases susceptibility to AZT-induced cardiomyopathy."],"offsets":[[0,88]]},{"id":"9151","type":"abstract","text":["BACKGROUND: Dilated cardiomyopathy (DCM) and myocarditis occur in many HIV-infected individuals, resulting in symptomatic heart failure in up to 5% of patients. Highly active antiretroviral therapy (HAART) has significantly reduced morbidity and mortality of acquired immunodeficiency syndrome (AIDS), but has resulted in an increase in cardiac and skeletal myopathies. METHODS AND RESULTS: In order to investigate whether the HAART component zidovudine (3'-azido-2',3'-deoxythymidine; AZT) triggers the Fas-dependent cell-death pathway and cause cytoskeletal disruption in a murine model of DCM, 8-week-old transgenic (expressing Fas ligand in the myocardium: FasL Tg) and non-transgenic (NTg) mice received water ad libitum containing different concentrations of AZT (0, 0.07, 0.2, and 0.7 mg\/ml). After 6 weeks, cardiac function was assessed by echocardiography and morphology was assessed by histopathologic and immunohistochemical methods. NTg and untreated FasL Tg mice showed little or no change in cardiac structure or function. In contrast, AZT-treated FasL Tg mice developed cardiac dilation and depressed cardiac function in a dose-dependent manner, with concomitant inflammatory infiltration of both ventricles. These changes were associated with an increased sarcolemmal expression of Fas and FasL, as well as increased activation of caspase 3, translocation of calpain 1 to the sarcolemma and sarcomere, and increased numbers of cells undergoing apoptosis. These were associated with changes in dystrophin and cardiac troponin I localization, as well as loss of sarcolemmal integrity. CONCLUSIONS: The expression of Fas ligand in the myocardium, as identified in HIV-positive patients, might increase the susceptibility to HAART-induced cardiomyopathy due to activation of apoptotic pathways, resulting in cardiac dilation and dysfunction."],"offsets":[[89,1942]]}],"entities":[{"id":"9152","type":"Chemical","text":["AZT"],"offsets":[[61,64]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"9153","type":"Disease","text":["cardiomyopathy"],"offsets":[[73,87]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"9154","type":"Disease","text":["Dilated cardiomyopathy"],"offsets":[[101,123]],"normalized":[{"db_name":"MESH","db_id":"D002311"}]},{"id":"9155","type":"Disease","text":["DCM"],"offsets":[[125,128]],"normalized":[{"db_name":"MESH","db_id":"D002311"}]},{"id":"9156","type":"Disease","text":["myocarditis"],"offsets":[[134,145]],"normalized":[{"db_name":"MESH","db_id":"D009205"}]},{"id":"9157","type":"Disease","text":["HIV-infected"],"offsets":[[160,172]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"9158","type":"Disease","text":["heart failure"],"offsets":[[211,224]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"9159","type":"Disease","text":["acquired immunodeficiency syndrome"],"offsets":[[348,382]],"normalized":[{"db_name":"MESH","db_id":"D000163"}]},{"id":"9160","type":"Disease","text":["AIDS"],"offsets":[[384,388]],"normalized":[{"db_name":"MESH","db_id":"D000163"}]},{"id":"9161","type":"Disease","text":["cardiac and skeletal myopathies"],"offsets":[[426,457]],"normalized":[{"db_name":"MESH","db_id":"C538496"}]},{"id":"9162","type":"Chemical","text":["zidovudine"],"offsets":[[532,542]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"9163","type":"Chemical","text":["3'-azido-2',3'-deoxythymidine"],"offsets":[[544,573]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"9164","type":"Chemical","text":["AZT"],"offsets":[[575,578]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"9165","type":"Disease","text":["DCM"],"offsets":[[681,684]],"normalized":[{"db_name":"MESH","db_id":"D002311"}]},{"id":"9166","type":"Chemical","text":["AZT"],"offsets":[[854,857]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"9167","type":"Chemical","text":["AZT"],"offsets":[[1139,1142]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"9168","type":"Disease","text":["cardiac dilation"],"offsets":[[1174,1190]],"normalized":[{"db_name":"MESH","db_id":"D002311"}]},{"id":"9169","type":"Disease","text":["cardiomyopathy"],"offsets":[[1840,1854]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"9170","type":"Disease","text":["cardiac dilation and dysfunction"],"offsets":[[1909,1941]],"normalized":[{"db_name":"MESH","db_id":"D002311"},{"db_name":"MESH","db_id":"D006331"}]},{"id":"9171","type":"Disease","text":["cardiac 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{"id":"9221","document_id":"17074608","passages":[{"id":"9222","type":"title","text":["Valproate-induced chorea and encephalopathy in atypical nonketotic hyperglycinemia."],"offsets":[[0,83]]},{"id":"9223","type":"abstract","text":["Nonketotic hyperglycinemia is a disorder of amino acid metabolism in which a defect in the glycine cleavage system leads to an accumulation of glycine in the brain and other body compartments. In the classical form it presents as neonatal apnea, intractable seizures, and hypotonia, followed by significant psychomotor retardation. An important subset of children with nonketotic hyperglycinemia are atypical variants who present in a heterogeneous manner. This report describes a patient with mild language delay and mental retardation, who was found to have nonketotic hyperglycinemia following her presentation with acute encephalopathy and chorea shortly after initiation of valproate therapy."],"offsets":[[84,781]]}],"entities":[{"id":"9224","type":"Chemical","text":["Valproate"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"9225","type":"Disease","text":["chorea"],"offsets":[[18,24]],"normalized":[{"db_name":"MESH","db_id":"D002819"}]},{"id":"9226","type":"Disease","text":["encephalopathy"],"offsets":[[29,43]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"9227","type":"Disease","text":["nonketotic hyperglycinemia"],"offsets":[[56,82]],"normalized":[{"db_name":"MESH","db_id":"D020158"}]},{"id":"9228","type":"Disease","text":["Nonketotic hyperglycinemia"],"offsets":[[84,110]],"normalized":[{"db_name":"MESH","db_id":"D020158"}]},{"id":"9229","type":"Disease","text":["disorder of amino acid metabolism"],"offsets":[[116,149]],"normalized":[{"db_name":"MESH","db_id":"D000592"}]},{"id":"9230","type":"Chemical","text":["glycine"],"offsets":[[175,182]],"normalized":[{"db_name":"MESH","db_id":"D005998"}]},{"id":"9231","type":"Chemical","text":["glycine"],"offsets":[[227,234]],"normalized":[{"db_name":"MESH","db_id":"D005998"}]},{"id":"9232","type":"Disease","text":["apnea"],"offsets":[[323,328]],"normalized":[{"db_name":"MESH","db_id":"D001049"}]},{"id":"9233","type":"Disease","text":["seizures"],"offsets":[[342,350]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"9234","type":"Disease","text":["hypotonia"],"offsets":[[356,365]],"normalized":[{"db_name":"MESH","db_id":"D009123"}]},{"id":"9235","type":"Disease","text":["psychomotor retardation"],"offsets":[[391,414]],"normalized":[{"db_name":"MESH","db_id":"D011596"}]},{"id":"9236","type":"Disease","text":["nonketotic hyperglycinemia"],"offsets":[[453,479]],"normalized":[{"db_name":"MESH","db_id":"D020158"}]},{"id":"9237","type":"Disease","text":["language delay"],"offsets":[[583,597]],"normalized":[{"db_name":"MESH","db_id":"D007805"}]},{"id":"9238","type":"Disease","text":["mental retardation"],"offsets":[[602,620]],"normalized":[{"db_name":"MESH","db_id":"D008607"}]},{"id":"9239","type":"Disease","text":["nonketotic hyperglycinemia"],"offsets":[[644,670]],"normalized":[{"db_name":"MESH","db_id":"D020158"}]},{"id":"9240","type":"Disease","text":["encephalopathy"],"offsets":[[709,723]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"9241","type":"Disease","text":["chorea"],"offsets":[[728,734]],"normalized":[{"db_name":"MESH","db_id":"D002819"}]},{"id":"9242","type":"Chemical","text":["valproate"],"offsets":[[763,772]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]}],"events":[],"coreferences":[],"relations":[{"id":"9243","type":"CID","arg1_id":"9224","arg2_id":"9225","normalized":[]},{"id":"9244","type":"CID","arg1_id":"9224","arg2_id":"9241","normalized":[]},{"id":"9245","type":"CID","arg1_id":"9242","arg2_id":"9225","normalized":[]},{"id":"9246","type":"CID","arg1_id":"9242","arg2_id":"9241","normalized":[]},{"id":"9247","type":"CID","arg1_id":"9224","arg2_id":"9226","normalized":[]},{"id":"9248","type":"CID","arg1_id":"9224","arg2_id":"9240","normalized":[]},{"id":"9249","type":"CID","arg1_id":"9242","arg2_id":"9226","normalized":[]},{"id":"9250","type":"CID","arg1_id":"9242","arg2_id":"9240","normalized":[]}]}
{"id":"9251","document_id":"16364460","passages":[{"id":"9252","type":"title","text":["Microinjection of ritanserin into the CA1 region of hippocampus improves scopolamine-induced amnesia in adult male rats."],"offsets":[[0,120]]},{"id":"9253","type":"abstract","text":["The effect of ritanserin (5-HT2 antagonist) on scopolamine (muscarinic cholinergic antagonist)-induced amnesia in Morris water maze (MWM) was investigated. Rats were divided into eight groups and bilaterally cannulated into CA1 region of the hippocampus. One week later, they received repeatedly vehicles (saline, DMSO, saline+DMSO), scopolamine (2 microg\/0.5 microl saline\/side; 30 min before training), ritanserin (2, 4 and 8 microg\/0.5 microl DMSO\/side; 20 min before training) and scopolamine (2 microg\/0.5 microl; 30 min before ritanserin injection)+ritanserin (4 microg\/0.5 microl DMSO) through cannulae each day. Animals were tested for four consecutive days (4 trial\/day) in MWM during which the position of hidden platform was unchanged. In the fifth day, the platform was elevated above the water surface in another position to evaluate the function of motor, motivational and visual systems. The results showed a significant increase in escape latencies and traveled distances to find platform in scopolamine-treated group as compared to saline group. Ritanserin-treated rats (4 microg\/0.5 microl\/side) showed a significant decrease in the mentioned parameters as compared to DMSO-treated group. However, scopolamine and ritanserin co-administration resulted in a significant decrease in escape latencies and traveled distances as compared to the scopolamine-treated rats. Our findings show that microinjection of ritanserin into the CA1 region of the hippocampus improves the scopolamine-induced amnesia."],"offsets":[[121,1637]]}],"entities":[{"id":"9254","type":"Chemical","text":["ritanserin"],"offsets":[[18,28]],"normalized":[{"db_name":"MESH","db_id":"D016713"}]},{"id":"9255","type":"Chemical","text":["scopolamine"],"offsets":[[73,84]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"9256","type":"Disease","text":["amnesia"],"offsets":[[93,100]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"9257","type":"Chemical","text":["ritanserin"],"offsets":[[135,145]],"normalized":[{"db_name":"MESH","db_id":"D016713"}]},{"id":"9258","type":"Chemical","text":["scopolamine"],"offsets":[[168,179]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"9259","type":"Disease","text":["amnesia"],"offsets":[[224,231]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"9260","type":"Chemical","text":["DMSO"],"offsets":[[435,439]],"normalized":[{"db_name":"MESH","db_id":"D004121"}]},{"id":"9261","type":"Chemical","text":["DMSO"],"offsets":[[448,452]],"normalized":[{"db_name":"MESH","db_id":"D004121"}]},{"id":"9262","type":"Chemical","text":["scopolamine"],"offsets":[[455,466]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"9263","type":"Chemical","text":["ritanserin"],"offsets":[[526,536]],"normalized":[{"db_name":"MESH","db_id":"D016713"}]},{"id":"9264","type":"Chemical","text":["DMSO"],"offsets":[[567,571]],"normalized":[{"db_name":"MESH","db_id":"D004121"}]},{"id":"9265","type":"Chemical","text":["scopolamine"],"offsets":[[606,617]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"9266","type":"Chemical","text":["ritanserin"],"offsets":[[654,664]],"normalized":[{"db_name":"MESH","db_id":"D016713"}]},{"id":"9267","type":"Chemical","text":["ritanserin"],"offsets":[[676,686]],"normalized":[{"db_name":"MESH","db_id":"D016713"}]},{"id":"9268","type":"Chemical","text":["DMSO"],"offsets":[[708,712]],"normalized":[{"db_name":"MESH","db_id":"D004121"}]},{"id":"9269","type":"Chemical","text":["scopolamine"],"offsets":[[1129,1140]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"9270","type":"Chemical","text":["Ritanserin"],"offsets":[[1184,1194]],"normalized":[{"db_name":"MESH","db_id":"D016713"}]},{"id":"9271","type":"Chemical","text":["DMSO"],"offsets":[[1308,1312]],"normalized":[{"db_name":"MESH","db_id":"D004121"}]},{"id":"9272","type":"Chemical","text":["scopolamine"],"offsets":[[1337,1348]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"9273","type":"Chemical","text":["ritanserin"],"offsets":[[1353,1363]],"normalized":[{"db_name":"MESH","db_id":"D016713"}]},{"id":"9274","type":"Chemical","text":["scopolamine"],"offsets":[[1479,1490]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"9275","type":"Chemical","text":["ritanserin"],"offsets":[[1546,1556]],"normalized":[{"db_name":"MESH","db_id":"D016713"}]},{"id":"9276","type":"Chemical","text":["scopolamine"],"offsets":[[1609,1620]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"9277","type":"Disease","text":["amnesia"],"offsets":[[1629,1636]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]}],"events":[],"coreferences":[],"relations":[{"id":"9278","type":"CID","arg1_id":"9255","arg2_id":"9256","normalized":[]},{"id":"9279","type":"CID","arg1_id":"9255","arg2_id":"9259","normalized":[]},{"id":"9280","type":"CID","arg1_id":"9255","arg2_id":"9277","normalized":[]},{"id":"9281","type":"CID","arg1_id":"9258","arg2_id":"9256","normalized":[]},{"id":"9282","type":"CID","arg1_id":"9258","arg2_id":"9259","normalized":[]},{"id":"9283","type":"CID","arg1_id":"9258","arg2_id":"9277","normalized":[]},{"id":"9284","type":"CID","arg1_id":"9262","arg2_id":"9256","normalized":[]},{"id":"9285","type":"CID","arg1_id":"9262","arg2_id":"9259","normalized":[]},{"id":"9286","type":"CID","arg1_id":"9262","arg2_id":"9277","normalized":[]},{"id":"9287","type":"CID","arg1_id":"9265","arg2_id":"9256","normalized":[]},{"id":"9288","type":"CID","arg1_id":"9265","arg2_id":"9259","normalized":[]},{"id":"9289","type":"CID","arg1_id":"9265","arg2_id":"9277","normalized":[]},{"id":"9290","type":"CID","arg1_id":"9269","arg2_id":"9256","normalized":[]},{"id":"9291","type":"CID","arg1_id":"9269","arg2_id":"9259","normalized":[]},{"id":"9292","type":"CID","arg1_id":"9269","arg2_id":"9277","normalized":[]},{"id":"9293","type":"CID","arg1_id":"9272","arg2_id":"9256","normalized":[]},{"id":"9294","type":"CID","arg1_id":"9272","arg2_id":"9259","normalized":[]},{"id":"9295","type":"CID","arg1_id":"9272","arg2_id":"9277","normalized":[]},{"id":"9296","type":"CID","arg1_id":"9274","arg2_id":"9256","normalized":[]},{"id":"9297","type":"CID","arg1_id":"9274","arg2_id":"9259","normalized":[]},{"id":"9298","type":"CID","arg1_id":"9274","arg2_id":"9277","normalized":[]},{"id":"9299","type":"CID","arg1_id":"9276","arg2_id":"9256","normalized":[]},{"id":"9300","type":"CID","arg1_id":"9276","arg2_id":"9259","normalized":[]},{"id":"9301","type":"CID","arg1_id":"9276","arg2_id":"9277","normalized":[]}]}
{"id":"9302","document_id":"15579441","passages":[{"id":"9303","type":"title","text":["Hypoxia in renal disease with proteinuria and\/or glomerular hypertension."],"offsets":[[0,73]]},{"id":"9304","type":"abstract","text":["Despite the increasing need to identify and quantify tissue oxygenation at the cellular level, relatively few methods have been available. In this study, we developed a new hypoxia-responsive reporter vector using a hypoxia-responsive element of the 5' vascular endothelial growth factor untranslated region and generated a novel hypoxia-sensing transgenic rat. We then applied this animal model to the detection of tubulointerstitial hypoxia in the diseased kidney. With this model, we were able to identify diffuse cortical hypoxia in the puromycin aminonucleoside-induced nephrotic syndrome and focal and segmental hypoxia in the remnant kidney model. Expression of the hypoxia-responsive transgene increased throughout the observation period, reaching 2.2-fold at 2 weeks in the puromycin aminonucleoside model and 2.6-fold at 4 weeks in the remnant kidney model, whereas that of vascular endothelial growth factor showed a mild decrease, reflecting distinct behaviors of the two genes. The degree of hypoxia showed a positive correlation with microscopic tubulointerstitial injury in both models. Finally, we identified the localization of proliferating cell nuclear antigen-positive, ED-1-positive, and terminal dUTP nick-end labeled-positive cells in the hypoxic cortical area in the remnant kidney model. We propose here a possible pathological tie between chronic tubulointerstitial hypoxia and progressive glomerular diseases."],"offsets":[[74,1510]]}],"entities":[{"id":"9305","type":"Disease","text":["Hypoxia"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D000860"}]},{"id":"9306","type":"Disease","text":["renal disease"],"offsets":[[11,24]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"9307","type":"Disease","text":["proteinuria"],"offsets":[[30,41]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"9308","type":"Disease","text":["hypertension"],"offsets":[[60,72]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"9309","type":"Disease","text":["hypoxia"],"offsets":[[247,254]],"normalized":[{"db_name":"MESH","db_id":"D000860"}]},{"id":"9310","type":"Disease","text":["hypoxia"],"offsets":[[290,297]],"normalized":[{"db_name":"MESH","db_id":"D000860"}]},{"id":"9311","type":"Disease","text":["hypoxia"],"offsets":[[404,411]],"normalized":[{"db_name":"MESH","db_id":"D000860"}]},{"id":"9312","type":"Disease","text":["hypoxia"],"offsets":[[509,516]],"normalized":[{"db_name":"MESH","db_id":"D000860"}]},{"id":"9313","type":"Disease","text":["diseased kidney"],"offsets":[[524,539]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"9314","type":"Disease","text":["hypoxia"],"offsets":[[600,607]],"normalized":[{"db_name":"MESH","db_id":"D000860"}]},{"id":"9315","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[615,640]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"9316","type":"Disease","text":["nephrotic syndrome"],"offsets":[[649,667]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]},{"id":"9317","type":"Disease","text":["hypoxia"],"offsets":[[692,699]],"normalized":[{"db_name":"MESH","db_id":"D000860"}]},{"id":"9318","type":"Disease","text":["hypoxia"],"offsets":[[747,754]],"normalized":[{"db_name":"MESH","db_id":"D000860"}]},{"id":"9319","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[857,882]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"9320","type":"Disease","text":["hypoxia"],"offsets":[[1079,1086]],"normalized":[{"db_name":"MESH","db_id":"D000860"}]},{"id":"9321","type":"Disease","text":["tubulointerstitial injury"],"offsets":[[1134,1159]],"normalized":[]},{"id":"9322","type":"Disease","text":["hypoxic"],"offsets":[[1336,1343]],"normalized":[{"db_name":"MESH","db_id":"D000860"}]},{"id":"9323","type":"Disease","text":["hypoxia"],"offsets":[[1466,1473]],"normalized":[{"db_name":"MESH","db_id":"D000860"}]},{"id":"9324","type":"Disease","text":["glomerular diseases"],"offsets":[[1490,1509]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"9325","type":"CID","arg1_id":"9315","arg2_id":"9305","normalized":[]},{"id":"9326","type":"CID","arg1_id":"9315","arg2_id":"9309","normalized":[]},{"id":"9327","type":"CID","arg1_id":"9315","arg2_id":"9310","normalized":[]},{"id":"9328","type":"CID","arg1_id":"9315","arg2_id":"9311","normalized":[]},{"id":"9329","type":"CID","arg1_id":"9315","arg2_id":"9312","normalized":[]},{"id":"9330","type":"CID","arg1_id":"9315","arg2_id":"9314","normalized":[]},{"id":"9331","type":"CID","arg1_id":"9315","arg2_id":"9317","normalized":[]},{"id":"9332","type":"CID","arg1_id":"9315","arg2_id":"9318","normalized":[]},{"id":"9333","type":"CID","arg1_id":"9315","arg2_id":"9320","normalized":[]},{"id":"9334","type":"CID","arg1_id":"9315","arg2_id":"9322","normalized":[]},{"id":"9335","type":"CID","arg1_id":"9315","arg2_id":"9323","normalized":[]},{"id":"9336","type":"CID","arg1_id":"9319","arg2_id":"9305","normalized":[]},{"id":"9337","type":"CID","arg1_id":"9319","arg2_id":"9309","normalized":[]},{"id":"9338","type":"CID","arg1_id":"9319","arg2_id":"9310","normalized":[]},{"id":"9339","type":"CID","arg1_id":"9319","arg2_id":"9311","normalized":[]},{"id":"9340","type":"CID","arg1_id":"9319","arg2_id":"9312","normalized":[]},{"id":"9341","type":"CID","arg1_id":"9319","arg2_id":"9314","normalized":[]},{"id":"9342","type":"CID","arg1_id":"9319","arg2_id":"9317","normalized":[]},{"id":"9343","type":"CID","arg1_id":"9319","arg2_id":"9318","normalized":[]},{"id":"9344","type":"CID","arg1_id":"9319","arg2_id":"9320","normalized":[]},{"id":"9345","type":"CID","arg1_id":"9319","arg2_id":"9322","normalized":[]},{"id":"9346","type":"CID","arg1_id":"9319","arg2_id":"9323","normalized":[]},{"id":"9347","type":"CID","arg1_id":"9315","arg2_id":"9316","normalized":[]},{"id":"9348","type":"CID","arg1_id":"9319","arg2_id":"9316","normalized":[]}]}
{"id":"9349","document_id":"15517007","passages":[{"id":"9350","type":"title","text":["Consensus statement concerning cardiotoxicity occurring during haematopoietic stem cell transplantation in the treatment of autoimmune diseases, with special reference to systemic sclerosis and multiple sclerosis."],"offsets":[[0,213]]},{"id":"9351","type":"abstract","text":["Autologous haematopoietic stem cell transplantation is now a feasible and effective treatment for selected patients with severe autoimmune diseases. Worldwide, over 650 patients have been transplanted in the context of phase I and II clinical trials. The results are encouraging enough to begin randomised phase III trials. However, as predicted, significant transplant-related morbidity and mortality have been observed. This is primarily due to complications related to either the stage of the disease at transplant or due to infections. The number of deaths related to cardiac toxicity is low. However, caution is required when cyclophosphamide or anthracyclines such as mitoxantrone are used in patients with a possible underlying heart damage, for example, systemic sclerosis patients. In November 2002, a meeting was held in Florence, bringing together a number of experts in various fields, including rheumatology, cardiology, neurology, pharmacology and transplantation medicine. The object of the meeting was to analyse existing data, both published or available, in the European Group for Blood and Marrow Transplantation autoimmune disease database, and to propose a safe approach to such patients. A full cardiological assessment before and during the transplant emerged as the major recommendation."],"offsets":[[214,1525]]}],"entities":[{"id":"9352","type":"Disease","text":["cardiotoxicity"],"offsets":[[31,45]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"9353","type":"Disease","text":["autoimmune diseases"],"offsets":[[124,143]],"normalized":[{"db_name":"MESH","db_id":"D001327"}]},{"id":"9354","type":"Disease","text":["systemic sclerosis"],"offsets":[[171,189]],"normalized":[{"db_name":"MESH","db_id":"D012595"}]},{"id":"9355","type":"Disease","text":["multiple sclerosis"],"offsets":[[194,212]],"normalized":[{"db_name":"MESH","db_id":"D009103"}]},{"id":"9356","type":"Disease","text":["autoimmune diseases"],"offsets":[[342,361]],"normalized":[{"db_name":"MESH","db_id":"D001327"}]},{"id":"9357","type":"Disease","text":["infections"],"offsets":[[742,752]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"9358","type":"Disease","text":["cardiac toxicity"],"offsets":[[786,802]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"9359","type":"Chemical","text":["cyclophosphamide"],"offsets":[[845,861]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"9360","type":"Chemical","text":["anthracyclines"],"offsets":[[865,879]],"normalized":[{"db_name":"MESH","db_id":"D018943"}]},{"id":"9361","type":"Chemical","text":["mitoxantrone"],"offsets":[[888,900]],"normalized":[{"db_name":"MESH","db_id":"D008942"}]},{"id":"9362","type":"Disease","text":["heart damage"],"offsets":[[949,961]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"9363","type":"Disease","text":["systemic sclerosis"],"offsets":[[976,994]],"normalized":[{"db_name":"MESH","db_id":"D012595"}]},{"id":"9364","type":"Disease","text":["autoimmune disease"],"offsets":[[1346,1364]],"normalized":[{"db_name":"MESH","db_id":"D001327"}]}],"events":[],"coreferences":[],"relations":[{"id":"9365","type":"CID","arg1_id":"9361","arg2_id":"9362","normalized":[]},{"id":"9366","type":"CID","arg1_id":"9359","arg2_id":"9362","normalized":[]}]}
{"id":"9367","document_id":"12180796","passages":[{"id":"9368","type":"title","text":["Immunohistochemical study on inducible type of nitric oxide (iNOS), basic fibroblast growth factor (bFGF) and tumor growth factor-beta1 (TGF-beta1) in arteritis induced in rats by fenoldopam and theophylline, vasodilators."],"offsets":[[0,222]]},{"id":"9369","type":"abstract","text":["Arteritis induced in rats by vasodilators, fenoldopam and theophylline, was examined immunohistochemically for expressions of inducible type of nitric oxide synthase (iNOS), basic fibroblast growth factor (bFGF) and tumor growth factor-beta1 (TGF-beta1). Rats were administered fenoldopam for 24 hours by intravenous infusion with or without following repeated daily oral administrations of theophylline. Irrespective of theophylline administration, iNOS antigens were remarkably abundant in ED-1-positive cells on day 5 and 8 post-fenoldopam-infusion (DPI); bFGF antigens were remarkably abundant in ED-1-positive cells on 1 and 3 DPI; TGF-beta1 antigens were observed in ED-1-positive cells on and after 5 DPI. These results suggest that the peak expression of iNOS antigen was followed by that of bFGF antigen, and bFGF may have a suppressive effect on iNOS expression in these rat arteritis models. On the other hand, TGF-beta1 was not considered to have a suppressive effect on iNOS expression in these models."],"offsets":[[223,1238]]}],"entities":[{"id":"9370","type":"Chemical","text":["nitric oxide"],"offsets":[[47,59]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"9371","type":"Disease","text":["tumor"],"offsets":[[110,115]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"9372","type":"Disease","text":["arteritis"],"offsets":[[151,160]],"normalized":[{"db_name":"MESH","db_id":"D001167"}]},{"id":"9373","type":"Chemical","text":["fenoldopam"],"offsets":[[180,190]],"normalized":[{"db_name":"MESH","db_id":"D018818"}]},{"id":"9374","type":"Chemical","text":["theophylline"],"offsets":[[195,207]],"normalized":[{"db_name":"MESH","db_id":"D013806"}]},{"id":"9375","type":"Disease","text":["Arteritis"],"offsets":[[223,232]],"normalized":[{"db_name":"MESH","db_id":"D001167"}]},{"id":"9376","type":"Chemical","text":["fenoldopam"],"offsets":[[266,276]],"normalized":[{"db_name":"MESH","db_id":"D018818"}]},{"id":"9377","type":"Chemical","text":["theophylline"],"offsets":[[281,293]],"normalized":[{"db_name":"MESH","db_id":"D013806"}]},{"id":"9378","type":"Chemical","text":["nitric oxide"],"offsets":[[367,379]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"9379","type":"Disease","text":["tumor"],"offsets":[[439,444]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"9380","type":"Chemical","text":["fenoldopam"],"offsets":[[501,511]],"normalized":[{"db_name":"MESH","db_id":"D018818"}]},{"id":"9381","type":"Chemical","text":["theophylline"],"offsets":[[614,626]],"normalized":[{"db_name":"MESH","db_id":"D013806"}]},{"id":"9382","type":"Chemical","text":["theophylline"],"offsets":[[644,656]],"normalized":[{"db_name":"MESH","db_id":"D013806"}]},{"id":"9383","type":"Chemical","text":["fenoldopam"],"offsets":[[755,765]],"normalized":[{"db_name":"MESH","db_id":"D018818"}]},{"id":"9384","type":"Disease","text":["arteritis"],"offsets":[[1108,1117]],"normalized":[{"db_name":"MESH","db_id":"D001167"}]}],"events":[],"coreferences":[],"relations":[{"id":"9385","type":"CID","arg1_id":"9373","arg2_id":"9372","normalized":[]},{"id":"9386","type":"CID","arg1_id":"9373","arg2_id":"9375","normalized":[]},{"id":"9387","type":"CID","arg1_id":"9373","arg2_id":"9384","normalized":[]},{"id":"9388","type":"CID","arg1_id":"9376","arg2_id":"9372","normalized":[]},{"id":"9389","type":"CID","arg1_id":"9376","arg2_id":"9375","normalized":[]},{"id":"9390","type":"CID","arg1_id":"9376","arg2_id":"9384","normalized":[]},{"id":"9391","type":"CID","arg1_id":"9380","arg2_id":"9372","normalized":[]},{"id":"9392","type":"CID","arg1_id":"9380","arg2_id":"9375","normalized":[]},{"id":"9393","type":"CID","arg1_id":"9380","arg2_id":"9384","normalized":[]},{"id":"9394","type":"CID","arg1_id":"9383","arg2_id":"9372","normalized":[]},{"id":"9395","type":"CID","arg1_id":"9383","arg2_id":"9375","normalized":[]},{"id":"9396","type":"CID","arg1_id":"9383","arg2_id":"9384","normalized":[]},{"id":"9397","type":"CID","arg1_id":"9374","arg2_id":"9372","normalized":[]},{"id":"9398","type":"CID","arg1_id":"9374","arg2_id":"9375","normalized":[]},{"id":"9399","type":"CID","arg1_id":"9374","arg2_id":"9384","normalized":[]},{"id":"9400","type":"CID","arg1_id":"9377","arg2_id":"9372","normalized":[]},{"id":"9401","type":"CID","arg1_id":"9377","arg2_id":"9375","normalized":[]},{"id":"9402","type":"CID","arg1_id":"9377","arg2_id":"9384","normalized":[]},{"id":"9403","type":"CID","arg1_id":"9381","arg2_id":"9372","normalized":[]},{"id":"9404","type":"CID","arg1_id":"9381","arg2_id":"9375","normalized":[]},{"id":"9405","type":"CID","arg1_id":"9381","arg2_id":"9384","normalized":[]},{"id":"9406","type":"CID","arg1_id":"9382","arg2_id":"9372","normalized":[]},{"id":"9407","type":"CID","arg1_id":"9382","arg2_id":"9375","normalized":[]},{"id":"9408","type":"CID","arg1_id":"9382","arg2_id":"9384","normalized":[]}]}
{"id":"9409","document_id":"12109865","passages":[{"id":"9410","type":"title","text":["Low-molecular-weight heparin for the treatment of patients with mechanical heart valves."],"offsets":[[0,88]]},{"id":"9411","type":"abstract","text":["BACKGROUND: The interruption of oral anticoagulant (OAC) administration is sometimes indicated in patients with mechanical heart valves, mainly before noncardiac surgery, non-surgical interventions, and pregnancy. Unfractionated heparin (UH) is currently the substitute for selected patients. Low-molecular-weight heparin (LMWH) offers theoretical advantages over UH, but is not currently considered in clinical guidelines as an alternative to UH in patients with prosthetic valves. HYPOTHESIS: The aim of the present study was to review the data accumulated so far on the use of LMWH in this patient population and to discuss its applicability in common practice. METHODS: For this paper, the current medical literature on LMWH in patients with mechanical heart valves was extensively reviewed. RESULTS: There were eight series and six case reports. None of the studies was randomized, and only one was prospective. Data to establish the thromboembolic risk were incomplete. After excluding case reports, the following groups were constructed: (a) short-term administration, after valve insertion (n = 212); (b) short-term, perioperative (noncardiac)\/periprocedural (n = 114); (c) long-term, due to intolerance to OAC (n = 16); (d) long-term, in pregnancy (n = 10). The incidence rate of thromboembolism was 0.9% for all the studies and 0.5, 0, 20, and 0% in groups a, b, c, and d, respectively; for hemorrhage, the overall rate was 3.4% (3.8, 2.6, 10, and 0% for the respective groups). CONCLUSIONS: In patients with mechanical heart valves, short-term LMWH therapy compares favorably with UH. Data on mid- and long-term LMWH administration in these patients are sparse. Further randomized studies are needed to confirm the safety and precise indications for the use of LMWH in patients with mechanical heart valves."],"offsets":[[89,1907]]}],"entities":[{"id":"9412","type":"Chemical","text":["Low-molecular-weight heparin"],"offsets":[[0,28]],"normalized":[{"db_name":"MESH","db_id":"D006495"}]},{"id":"9413","type":"Chemical","text":["Unfractionated heparin"],"offsets":[[303,325]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"9414","type":"Chemical","text":["UH"],"offsets":[[327,329]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"9415","type":"Chemical","text":["Low-molecular-weight heparin"],"offsets":[[382,410]],"normalized":[{"db_name":"MESH","db_id":"D006495"}]},{"id":"9416","type":"Chemical","text":["LMWH"],"offsets":[[412,416]],"normalized":[{"db_name":"MESH","db_id":"D006495"}]},{"id":"9417","type":"Chemical","text":["UH"],"offsets":[[453,455]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"9418","type":"Chemical","text":["UH"],"offsets":[[533,535]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"9419","type":"Chemical","text":["LMWH"],"offsets":[[669,673]],"normalized":[{"db_name":"MESH","db_id":"D006495"}]},{"id":"9420","type":"Chemical","text":["LMWH"],"offsets":[[813,817]],"normalized":[{"db_name":"MESH","db_id":"D006495"}]},{"id":"9421","type":"Disease","text":["thromboembolic"],"offsets":[[1028,1042]],"normalized":[{"db_name":"MESH","db_id":"D013923"}]},{"id":"9422","type":"Disease","text":["thromboembolism"],"offsets":[[1378,1393]],"normalized":[{"db_name":"MESH","db_id":"D013923"}]},{"id":"9423","type":"Disease","text":["hemorrhage"],"offsets":[[1490,1500]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"9424","type":"Chemical","text":["LMWH"],"offsets":[[1644,1648]],"normalized":[{"db_name":"MESH","db_id":"D006495"}]},{"id":"9425","type":"Chemical","text":["UH"],"offsets":[[1681,1683]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"9426","type":"Chemical","text":["LMWH"],"offsets":[[1712,1716]],"normalized":[{"db_name":"MESH","db_id":"D006495"}]},{"id":"9427","type":"Chemical","text":["LMWH"],"offsets":[[1861,1865]],"normalized":[{"db_name":"MESH","db_id":"D006495"}]}],"events":[],"coreferences":[],"relations":[{"id":"9428","type":"CID","arg1_id":"9412","arg2_id":"9423","normalized":[]},{"id":"9429","type":"CID","arg1_id":"9415","arg2_id":"9423","normalized":[]},{"id":"9430","type":"CID","arg1_id":"9416","arg2_id":"9423","normalized":[]},{"id":"9431","type":"CID","arg1_id":"9419","arg2_id":"9423","normalized":[]},{"id":"9432","type":"CID","arg1_id":"9420","arg2_id":"9423","normalized":[]},{"id":"9433","type":"CID","arg1_id":"9424","arg2_id":"9423","normalized":[]},{"id":"9434","type":"CID","arg1_id":"9426","arg2_id":"9423","normalized":[]},{"id":"9435","type":"CID","arg1_id":"9427","arg2_id":"9423","normalized":[]},{"id":"9436","type":"CID","arg1_id":"9412","arg2_id":"9421","normalized":[]},{"id":"9437","type":"CID","arg1_id":"9412","arg2_id":"9422","normalized":[]},{"id":"9438","type":"CID","arg1_id":"9415","arg2_id":"9421","normalized":[]},{"id":"9439","type":"CID","arg1_id":"9415","arg2_id":"9422","normalized":[]},{"id":"9440","type":"CID","arg1_id":"9416","arg2_id":"9421","normalized":[]},{"id":"9441","type":"CID","arg1_id":"9416","arg2_id":"9422","normalized":[]},{"id":"9442","type":"CID","arg1_id":"9419","arg2_id":"9421","normalized":[]},{"id":"9443","type":"CID","arg1_id":"9419","arg2_id":"9422","normalized":[]},{"id":"9444","type":"CID","arg1_id":"9420","arg2_id":"9421","normalized":[]},{"id":"9445","type":"CID","arg1_id":"9420","arg2_id":"9422","normalized":[]},{"id":"9446","type":"CID","arg1_id":"9424","arg2_id":"9421","normalized":[]},{"id":"9447","type":"CID","arg1_id":"9424","arg2_id":"9422","normalized":[]},{"id":"9448","type":"CID","arg1_id":"9426","arg2_id":"9421","normalized":[]},{"id":"9449","type":"CID","arg1_id":"9426","arg2_id":"9422","normalized":[]},{"id":"9450","type":"CID","arg1_id":"9427","arg2_id":"9421","normalized":[]},{"id":"9451","type":"CID","arg1_id":"9427","arg2_id":"9422","normalized":[]}]}
{"id":"9452","document_id":"12042105","passages":[{"id":"9453","type":"title","text":["Topiramate-induced nephrolithiasis."],"offsets":[[0,35]]},{"id":"9454","type":"abstract","text":["Topiramate is a recently developed antiepileptic medication that is becoming more widely prescribed because of its efficacy in treating refractory seizures. Urologists should be aware that this medication can cause metabolic acidosis in patients secondary to inhibition of carbonic anhydrase. In addition, a distal tubular acidification defect may result, thus impairing the normal compensatory drop in urine pH. These factors can lead to the development of calcium phosphate nephrolithiasis. We report the first two cases of topiramate-induced nephrolithiasis in the urologic literature."],"offsets":[[36,624]]}],"entities":[{"id":"9455","type":"Chemical","text":["Topiramate"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"C052342"}]},{"id":"9456","type":"Disease","text":["nephrolithiasis"],"offsets":[[19,34]],"normalized":[{"db_name":"MESH","db_id":"D053040"}]},{"id":"9457","type":"Chemical","text":["Topiramate"],"offsets":[[36,46]],"normalized":[{"db_name":"MESH","db_id":"C052342"}]},{"id":"9458","type":"Disease","text":["refractory seizures"],"offsets":[[172,191]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"9459","type":"Disease","text":["metabolic acidosis"],"offsets":[[251,269]],"normalized":[{"db_name":"MESH","db_id":"D000138"}]},{"id":"9460","type":"Chemical","text":["calcium phosphate"],"offsets":[[494,511]],"normalized":[{"db_name":"MESH","db_id":"C020243"}]},{"id":"9461","type":"Disease","text":["nephrolithiasis"],"offsets":[[512,527]],"normalized":[{"db_name":"MESH","db_id":"D053040"}]},{"id":"9462","type":"Chemical","text":["topiramate"],"offsets":[[562,572]],"normalized":[{"db_name":"MESH","db_id":"C052342"}]},{"id":"9463","type":"Disease","text":["nephrolithiasis"],"offsets":[[581,596]],"normalized":[{"db_name":"MESH","db_id":"D053040"}]}],"events":[],"coreferences":[],"relations":[{"id":"9464","type":"CID","arg1_id":"9455","arg2_id":"9456","normalized":[]},{"id":"9465","type":"CID","arg1_id":"9455","arg2_id":"9461","normalized":[]},{"id":"9466","type":"CID","arg1_id":"9455","arg2_id":"9463","normalized":[]},{"id":"9467","type":"CID","arg1_id":"9457","arg2_id":"9456","normalized":[]},{"id":"9468","type":"CID","arg1_id":"9457","arg2_id":"9461","normalized":[]},{"id":"9469","type":"CID","arg1_id":"9457","arg2_id":"9463","normalized":[]},{"id":"9470","type":"CID","arg1_id":"9462","arg2_id":"9456","normalized":[]},{"id":"9471","type":"CID","arg1_id":"9462","arg2_id":"9461","normalized":[]},{"id":"9472","type":"CID","arg1_id":"9462","arg2_id":"9463","normalized":[]}]}
{"id":"9473","document_id":"11868798","passages":[{"id":"9474","type":"title","text":["Spironolactone: is it a novel drug for the prevention of amphotericin B-related hypokalemia in cancer patients?"],"offsets":[[0,111]]},{"id":"9475","type":"abstract","text":["OBJECTIVE: Nephrotoxicity is the major adverse effect of amphotericin B (AmB), often limiting administration of full dosage. Selective distal tubular epithelial toxicity seems to be responsible for the profound potassium wasting that is a major clinical side effect of treatment with AmB. Potassium depletion also potentiates the tubular toxicity of AmB. This study was designed to assess the ability of spironolactone to reduce potassium requirements and to prevent hypokalemia in neutropenic patients on AmB treatment. METHODS: In this study 26 patients with various hematological disorders were randomized to receive either intravenous AmB alone or AmB and oral spironolactone 100 mg twice daily when developing a proven or suspected fungal infection. RESULTS: Patients receiving concomitant AmB and spironolactone had significantly higher plasma potassium levels than those receiving AmB alone (P = 0.0027). Those patients receiving AmB and spironolactone required significantly less potassium supplementation to maintain their plasma potassium within the normal range (P = 0.022). Moreover, urinary potassium losses were significantly less in patients receiving AmB and spironolactone than those receiving AmB alone (P = 0.040). CONCLUSION: This study showed that spironolactone can reduce potassium requirements and prevent hypokalemia by reducing urinary potassium loss in neutropenic patients on AmB treatment."],"offsets":[[112,1530]]}],"entities":[{"id":"9476","type":"Chemical","text":["Spironolactone"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D013148"}]},{"id":"9477","type":"Chemical","text":["amphotericin B"],"offsets":[[57,71]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"9478","type":"Disease","text":["hypokalemia"],"offsets":[[80,91]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"9479","type":"Disease","text":["cancer"],"offsets":[[95,101]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"9480","type":"Disease","text":["Nephrotoxicity"],"offsets":[[123,137]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"9481","type":"Chemical","text":["amphotericin B"],"offsets":[[169,183]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"9482","type":"Chemical","text":["AmB"],"offsets":[[185,188]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"9483","type":"Disease","text":["toxicity"],"offsets":[[273,281]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"9484","type":"Chemical","text":["potassium"],"offsets":[[323,332]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"9485","type":"Chemical","text":["AmB"],"offsets":[[396,399]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"9486","type":"Chemical","text":["Potassium"],"offsets":[[401,410]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"9487","type":"Disease","text":["toxicity"],"offsets":[[450,458]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"9488","type":"Chemical","text":["AmB"],"offsets":[[462,465]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"9489","type":"Chemical","text":["spironolactone"],"offsets":[[516,530]],"normalized":[{"db_name":"MESH","db_id":"D013148"}]},{"id":"9490","type":"Chemical","text":["potassium"],"offsets":[[541,550]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"9491","type":"Disease","text":["hypokalemia"],"offsets":[[579,590]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"9492","type":"Disease","text":["neutropenic"],"offsets":[[594,605]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"9493","type":"Chemical","text":["AmB"],"offsets":[[618,621]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"9494","type":"Disease","text":["hematological disorders"],"offsets":[[681,704]],"normalized":[{"db_name":"MESH","db_id":"D006402"}]},{"id":"9495","type":"Chemical","text":["AmB"],"offsets":[[751,754]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"9496","type":"Chemical","text":["AmB"],"offsets":[[764,767]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"9497","type":"Chemical","text":["spironolactone"],"offsets":[[777,791]],"normalized":[{"db_name":"MESH","db_id":"D013148"}]},{"id":"9498","type":"Disease","text":["fungal infection"],"offsets":[[849,865]],"normalized":[{"db_name":"MESH","db_id":"D009181"}]},{"id":"9499","type":"Chemical","text":["AmB"],"offsets":[[907,910]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"9500","type":"Chemical","text":["spironolactone"],"offsets":[[915,929]],"normalized":[{"db_name":"MESH","db_id":"D013148"}]},{"id":"9501","type":"Chemical","text":["potassium"],"offsets":[[962,971]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"9502","type":"Chemical","text":["AmB"],"offsets":[[1000,1003]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"9503","type":"Chemical","text":["AmB"],"offsets":[[1049,1052]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"9504","type":"Chemical","text":["spironolactone"],"offsets":[[1057,1071]],"normalized":[{"db_name":"MESH","db_id":"D013148"}]},{"id":"9505","type":"Chemical","text":["potassium"],"offsets":[[1100,1109]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"9506","type":"Chemical","text":["potassium"],"offsets":[[1151,1160]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"9507","type":"Chemical","text":["potassium"],"offsets":[[1216,1225]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"9508","type":"Chemical","text":["AmB"],"offsets":[[1279,1282]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"9509","type":"Chemical","text":["spironolactone"],"offsets":[[1287,1301]],"normalized":[{"db_name":"MESH","db_id":"D013148"}]},{"id":"9510","type":"Chemical","text":["AmB"],"offsets":[[1323,1326]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]},{"id":"9511","type":"Chemical","text":["spironolactone"],"offsets":[[1381,1395]],"normalized":[{"db_name":"MESH","db_id":"D013148"}]},{"id":"9512","type":"Chemical","text":["potassium"],"offsets":[[1407,1416]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"9513","type":"Disease","text":["hypokalemia"],"offsets":[[1442,1453]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"9514","type":"Chemical","text":["potassium"],"offsets":[[1474,1483]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"9515","type":"Disease","text":["neutropenic"],"offsets":[[1492,1503]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"9516","type":"Chemical","text":["AmB"],"offsets":[[1516,1519]],"normalized":[{"db_name":"MESH","db_id":"D000666"}]}],"events":[],"coreferences":[],"relations":[{"id":"9517","type":"CID","arg1_id":"9477","arg2_id":"9478","normalized":[]},{"id":"9518","type":"CID","arg1_id":"9477","arg2_id":"9491","normalized":[]},{"id":"9519","type":"CID","arg1_id":"9477","arg2_id":"9513","normalized":[]},{"id":"9520","type":"CID","arg1_id":"9481","arg2_id":"9478","normalized":[]},{"id":"9521","type":"CID","arg1_id":"9481","arg2_id":"9491","normalized":[]},{"id":"9522","type":"CID","arg1_id":"9481","arg2_id":"9513","normalized":[]},{"id":"9523","type":"CID","arg1_id":"9482","arg2_id":"9478","normalized":[]},{"id":"9524","type":"CID","arg1_id":"9482","arg2_id":"9491","normalized":[]},{"id":"9525","type":"CID","arg1_id":"9482","arg2_id":"9513","normalized":[]},{"id":"9526","type":"CID","arg1_id":"9485","arg2_id":"9478","normalized":[]},{"id":"9527","type":"CID","arg1_id":"9485","arg2_id":"9491","normalized":[]},{"id":"9528","type":"CID","arg1_id":"9485","arg2_id":"9513","normalized":[]},{"id":"9529","type":"CID","arg1_id":"9488","arg2_id":"9478","normalized":[]},{"id":"9530","type":"CID","arg1_id":"9488","arg2_id":"9491","normalized":[]},{"id":"9531","type":"CID","arg1_id":"9488","arg2_id":"9513","normalized":[]},{"id":"9532","type":"CID","arg1_id":"9493","arg2_id":"9478","normalized":[]},{"id":"9533","type":"CID","arg1_id":"9493","arg2_id":"9491","normalized":[]},{"id":"9534","type":"CID","arg1_id":"9493","arg2_id":"9513","normalized":[]},{"id":"9535","type":"CID","arg1_id":"9495","arg2_id":"9478","normalized":[]},{"id":"9536","type":"CID","arg1_id":"9495","arg2_id":"9491","normalized":[]},{"id":"9537","type":"CID","arg1_id":"9495","arg2_id":"9513","normalized":[]},{"id":"9538","type":"CID","arg1_id":"9496","arg2_id":"9478","normalized":[]},{"id":"9539","type":"CID","arg1_id":"9496","arg2_id":"9491","normalized":[]},{"id":"9540","type":"CID","arg1_id":"9496","arg2_id":"9513","normalized":[]},{"id":"9541","type":"CID","arg1_id":"9499","arg2_id":"9478","normalized":[]},{"id":"9542","type":"CID","arg1_id":"9499","arg2_id":"9491","normalized":[]},{"id":"9543","type":"CID","arg1_id":"9499","arg2_id":"9513","normalized":[]},{"id":"9544","type":"CID","arg1_id":"9502","arg2_id":"9478","normalized":[]},{"id":"9545","type":"CID","arg1_id":"9502","arg2_id":"9491","normalized":[]},{"id":"9546","type":"CID","arg1_id":"9502","arg2_id":"9513","normalized":[]},{"id":"9547","type":"CID","arg1_id":"9503","arg2_id":"9478","normalized":[]},{"id":"9548","type":"CID","arg1_id":"9503","arg2_id":"9491","normalized":[]},{"id":"9549","type":"CID","arg1_id":"9503","arg2_id":"9513","normalized":[]},{"id":"9550","type":"CID",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{"id":"9559","document_id":"11860278","passages":[{"id":"9560","type":"title","text":["Dopamine D2 receptor signaling controls neuronal cell death induced by muscarinic and glutamatergic drugs."],"offsets":[[0,106]]},{"id":"9561","type":"abstract","text":["Dopamine (DA), through D1\/D2 receptor-mediated signaling, plays a major role in the control of epileptic seizures arising in the limbic system. Excitotoxicity leading to neuronal cell death in the affected areas is a major consequence of seizures at the cellular level. In this respect, little is known about the role of DA receptors in the occurrence of epilepsy-induced neuronal cell death. Here we analyze the occurrence of seizures and neurotoxicity in D2R -\/- mice treated with the cholinergic agonist pilocarpine. We compared these results with those previously obtained with kainic acid (KA), a potent glutamate agonist. Importantly, D2R -\/- mice develop seizures at doses of both drugs that are not epileptogenic for WT littermates and show greater neurotoxicity. However, pilocarpine-induced seizures result in a more widespread neuronal death in both WT and D2R -\/- brains in comparison to KA. Thus, the absence of D2R lowers the threshold for seizures induced by both glutamate and acetylcholine. Moreover, the dopaminergic control of epilepsy-induced neurodegeneration seems to be mediated by distinct interactions of D2R signaling with these two neurotransmitters."],"offsets":[[107,1284]]}],"entities":[{"id":"9562","type":"Chemical","text":["Dopamine"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"9563","type":"Chemical","text":["Dopamine"],"offsets":[[107,115]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"9564","type":"Chemical","text":["DA"],"offsets":[[117,119]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"9565","type":"Disease","text":["epileptic seizures"],"offsets":[[202,220]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"9566","type":"Disease","text":["Excitotoxicity"],"offsets":[[251,265]],"normalized":[]},{"id":"9567","type":"Disease","text":["seizures"],"offsets":[[345,353]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"9568","type":"Chemical","text":["DA"],"offsets":[[428,430]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"9569","type":"Disease","text":["epilepsy"],"offsets":[[462,470]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"9570","type":"Disease","text":["seizures"],"offsets":[[534,542]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"9571","type":"Disease","text":["neurotoxicity"],"offsets":[[547,560]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"9572","type":"Chemical","text":["pilocarpine"],"offsets":[[614,625]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"9573","type":"Chemical","text":["kainic acid"],"offsets":[[689,700]],"normalized":[{"db_name":"MESH","db_id":"D007608"}]},{"id":"9574","type":"Chemical","text":["KA"],"offsets":[[702,704]],"normalized":[{"db_name":"MESH","db_id":"D007608"}]},{"id":"9575","type":"Chemical","text":["glutamate"],"offsets":[[716,725]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"9576","type":"Disease","text":["seizures"],"offsets":[[769,777]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"9577","type":"Disease","text":["neurotoxicity"],"offsets":[[864,877]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"9578","type":"Chemical","text":["pilocarpine"],"offsets":[[888,899]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"9579","type":"Disease","text":["seizures"],"offsets":[[908,916]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"9580","type":"Chemical","text":["KA"],"offsets":[[1007,1009]],"normalized":[{"db_name":"MESH","db_id":"D007608"}]},{"id":"9581","type":"Disease","text":["seizures"],"offsets":[[1061,1069]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"9582","type":"Chemical","text":["glutamate"],"offsets":[[1086,1095]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"9583","type":"Chemical","text":["acetylcholine"],"offsets":[[1100,1113]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"9584","type":"Disease","text":["epilepsy"],"offsets":[[1153,1161]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"9585","type":"Disease","text":["neurodegeneration"],"offsets":[[1170,1187]],"normalized":[{"db_name":"MESH","db_id":"D019636"}]}],"events":[],"coreferences":[],"relations":[{"id":"9586","type":"CID","arg1_id":"9572","arg2_id":"9567","normalized":[]},{"id":"9587","type":"CID","arg1_id":"9572","arg2_id":"9570","normalized":[]},{"id":"9588","type":"CID","arg1_id":"9572","arg2_id":"9576","normalized":[]},{"id":"9589","type":"CID","arg1_id":"9572","arg2_id":"9579","normalized":[]},{"id":"9590","type":"CID","arg1_id":"9572","arg2_id":"9581","normalized":[]},{"id":"9591","type":"CID","arg1_id":"9578","arg2_id":"9567","normalized":[]},{"id":"9592","type":"CID","arg1_id":"9578","arg2_id":"9570","normalized":[]},{"id":"9593","type":"CID","arg1_id":"9578","arg2_id":"9576","normalized":[]},{"id":"9594","type":"CID","arg1_id":"9578","arg2_id":"9579","normalized":[]},{"id":"9595","type":"CID","arg1_id":"9578","arg2_id":"9581","normalized":[]},{"id":"9596","type":"CID","arg1_id":"9573","arg2_id":"9567","normalized":[]},{"id":"9597","type":"CID","arg1_id":"9573","arg2_id":"9570","normalized":[]},{"id":"9598","type":"CID","arg1_id":"9573","arg2_id":"9576","normalized":[]},{"id":"9599","type":"CID","arg1_id":"9573","arg2_id":"9579","normalized":[]},{"id":"9600","type":"CID","arg1_id":"9573","arg2_id":"9581","normalized":[]},{"id":"9601","type":"CID","arg1_id":"9574","arg2_id":"9567","normalized":[]},{"id":"9602","type":"CID","arg1_id":"9574","arg2_id":"9570","normalized":[]},{"id":"9603","type":"CID","arg1_id":"9574","arg2_id":"9576","normalized":[]},{"id":"9604","type":"CID","arg1_id":"9574","arg2_id":"9579","normalized":[]},{"id":"9605","type":"CID","arg1_id":"9574","arg2_id":"9581","normalized":[]},{"id":"9606","type":"CID","arg1_id":"9580","arg2_id":"9567","normalized":[]},{"id":"9607","type":"CID","arg1_id":"9580","arg2_id":"9570","normalized":[]},{"id":"9608","type":"CID","arg1_id":"9580","arg2_id":"9576","normalized":[]},{"id":"9609","type":"CID","arg1_id":"9580","arg2_id":"9579","normalized":[]},{"id":"9610","type":"CID","arg1_id":"9580","arg2_id":"9581","normalized":[]}]}
{"id":"9611","document_id":"11838826","passages":[{"id":"9612","type":"title","text":["Treatment of risperidone-induced hyperprolactinemia with a dopamine agonist in children."],"offsets":[[0,88]]},{"id":"9613","type":"abstract","text":["BACKGROUND: Risperidone, a potent antagonist of both serotonergic (5HT2A) and dopaminergic D2 receptors is associated with hyperprolactinemia in adults and children. Chronically elevated prolactin levels in children with prolactinomas may be associated with arrested growth and development resulting in either delayed puberty or short stature. These possibilities stress the importance of developing a safe and effective approach to drug-induced hyperprolactinemia in youth. We report the successful treatment of risperidone-induced hyperprolactinemia with cabergoline in youth. METHODS: We undertook a retrospective case review of four children with risperidone-induced hyperprolactinemia treated with cabergoline. RESULTS: Four males (age 6-11 years) with Diagnostic and Statistical Manual of Mental Disorders (fourth edition) bipolar disorder or psychoses, with risperidone-induced elevations in serum prolactin levels (57.5-129 ng\/mL, normal 5-15 ng\/mL), were treated with cabergoline (mean dose 2.13 +\/- 0.09 mg\/week). When serum prolactin levels normalized in all four subjects (mean 11.2 +\/- 10.9 ng\/mL), the cabergoline dose was reduced to 1 mg\/week in three of four subjects. The mean duration of therapy with cabergoline was 523.5 +\/- 129.7 days, and the mean duration of therapy with risperidone was 788.5 +\/- 162.5 days. Cabergoline was well tolerated without adverse effects. CONCLUSIONS: Cabergoline may be useful for the treatment of risperidone-induced hyperprolactinemia in youth; however, further research is needed."],"offsets":[[89,1623]]}],"entities":[{"id":"9614","type":"Chemical","text":["risperidone"],"offsets":[[13,24]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"9615","type":"Disease","text":["hyperprolactinemia"],"offsets":[[33,51]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"9616","type":"Chemical","text":["dopamine"],"offsets":[[59,67]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"9617","type":"Chemical","text":["Risperidone"],"offsets":[[101,112]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"9618","type":"Disease","text":["hyperprolactinemia"],"offsets":[[212,230]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"9619","type":"Disease","text":["prolactinomas"],"offsets":[[310,323]],"normalized":[{"db_name":"MESH","db_id":"D015175"}]},{"id":"9620","type":"Disease","text":["delayed puberty"],"offsets":[[399,414]],"normalized":[{"db_name":"MESH","db_id":"D011628"}]},{"id":"9621","type":"Disease","text":["hyperprolactinemia"],"offsets":[[535,553]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"9622","type":"Chemical","text":["risperidone"],"offsets":[[602,613]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"9623","type":"Disease","text":["hyperprolactinemia"],"offsets":[[622,640]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"9624","type":"Chemical","text":["cabergoline"],"offsets":[[646,657]],"normalized":[{"db_name":"MESH","db_id":"C047047"}]},{"id":"9625","type":"Chemical","text":["risperidone"],"offsets":[[740,751]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"9626","type":"Disease","text":["hyperprolactinemia"],"offsets":[[760,778]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"9627","type":"Chemical","text":["cabergoline"],"offsets":[[792,803]],"normalized":[{"db_name":"MESH","db_id":"C047047"}]},{"id":"9628","type":"Disease","text":["Mental Disorders"],"offsets":[[884,900]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"9629","type":"Disease","text":["bipolar 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{"id":"9682","document_id":"11467664","passages":[{"id":"9683","type":"title","text":["Cholestatic jaundice associated with the use of metformin."],"offsets":[[0,58]]},{"id":"9684","type":"abstract","text":["We report a patient who developed cholestatic jaundice shortly after initiation of treatment with metformin hydrochloride. Ultrasound of the liver and abdominal CT were normal. An ERCP showed normal biliary anatomy. A percutaneous liver biopsy was obtained showing marked cholestasis, with portal edema, ductular proliferation, and acute inflammation. Metformin hydrochloride was discontinued, and the patient's jaundice resolved slowly over a period of several months. Given the onset of his jaundice 2 wk after the initiation of metformin, we believe that this case represents an example of metformin-associated hepatotoxicity, the first such case reported."],"offsets":[[59,718]]}],"entities":[{"id":"9685","type":"Disease","text":["Cholestatic jaundice"],"offsets":[[0,20]],"normalized":[{"db_name":"MESH","db_id":"D041781"}]},{"id":"9686","type":"Chemical","text":["metformin"],"offsets":[[48,57]],"normalized":[{"db_name":"MESH","db_id":"D008687"}]},{"id":"9687","type":"Disease","text":["cholestatic jaundice"],"offsets":[[93,113]],"normalized":[{"db_name":"MESH","db_id":"D041781"}]},{"id":"9688","type":"Chemical","text":["metformin hydrochloride"],"offsets":[[157,180]],"normalized":[{"db_name":"MESH","db_id":"D008687"}]},{"id":"9689","type":"Disease","text":["cholestasis"],"offsets":[[331,342]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"9690","type":"Disease","text":["edema"],"offsets":[[356,361]],"normalized":[{"db_name":"MESH","db_id":"D004487"}]},{"id":"9691","type":"Disease","text":["inflammation"],"offsets":[[397,409]],"normalized":[{"db_name":"MESH","db_id":"D007249"}]},{"id":"9692","type":"Chemical","text":["Metformin hydrochloride"],"offsets":[[411,434]],"normalized":[{"db_name":"MESH","db_id":"D008687"}]},{"id":"9693","type":"Disease","text":["jaundice"],"offsets":[[471,479]],"normalized":[{"db_name":"MESH","db_id":"D007565"}]},{"id":"9694","type":"Disease","text":["jaundice"],"offsets":[[552,560]],"normalized":[{"db_name":"MESH","db_id":"D007565"}]},{"id":"9695","type":"Chemical","text":["metformin"],"offsets":[[590,599]],"normalized":[{"db_name":"MESH","db_id":"D008687"}]},{"id":"9696","type":"Chemical","text":["metformin"],"offsets":[[652,661]],"normalized":[{"db_name":"MESH","db_id":"D008687"}]},{"id":"9697","type":"Disease","text":["hepatotoxicity"],"offsets":[[673,687]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]}],"events":[],"coreferences":[],"relations":[{"id":"9698","type":"CID","arg1_id":"9686","arg2_id":"9685","normalized":[]},{"id":"9699","type":"CID","arg1_id":"9686","arg2_id":"9687","normalized":[]},{"id":"9700","type":"CID","arg1_id":"9688","arg2_id":"9685","normalized":[]},{"id":"9701","type":"CID","arg1_id":"9688","arg2_id":"9687","normalized":[]},{"id":"9702","type":"CID","arg1_id":"9692","arg2_id":"9685","normalized":[]},{"id":"9703","type":"CID","arg1_id":"9692","arg2_id":"9687","normalized":[]},{"id":"9704","type":"CID","arg1_id":"9695","arg2_id":"9685","normalized":[]},{"id":"9705","type":"CID","arg1_id":"9695","arg2_id":"9687","normalized":[]},{"id":"9706","type":"CID","arg1_id":"9696","arg2_id":"9685","normalized":[]},{"id":"9707","type":"CID","arg1_id":"9696","arg2_id":"9687","normalized":[]},{"id":"9708","type":"CID","arg1_id":"9686","arg2_id":"9689","normalized":[]},{"id":"9709","type":"CID","arg1_id":"9688","arg2_id":"9689","normalized":[]},{"id":"9710","type":"CID","arg1_id":"9692","arg2_id":"9689","normalized":[]},{"id":"9711","type":"CID","arg1_id":"9695","arg2_id":"9689","normalized":[]},{"id":"9712","type":"CID","arg1_id":"9696","arg2_id":"9689","normalized":[]}]}
{"id":"9713","document_id":"11077455","passages":[{"id":"9714","type":"title","text":["Electro-oculography, electroretinography, visual evoked potentials, and multifocal electroretinography in patients with vigabatrin-attributed visual field constriction."],"offsets":[[0,168]]},{"id":"9715","type":"abstract","text":["PURPOSE: Symptomatic visual field constriction thought to be associated with vigabatrin has been reported. The current study investigated the visual fields and visual electrophysiology of eight patients with known vigabatrin-attributed visual field loss, three of whom were reported previously. Six of the patients were no longer receiving vigabatrin. METHODS: The central and peripheral fields were examined with the Humphrey Visual Field Analyzer. Full visual electrophysiology, including flash electroretinography (ERG), pattern electroretinography, multifocal ERG using the VERIS system, electro-oculography, and flash and pattern visual evoked potentials, was undertaken. RESULTS: Seven patients showed marked visual field constriction with some sparing of the temporal visual field. The eighth exhibited concentric constriction. Most electrophysiological responses were usually just within normal limits; two patients had subnormal Arden electro-oculography indices; and one patient showed an abnormally delayed photopic b wave. However, five patients showed delayed 30-Hz flicker b waves, and seven patients showed delayed oscillatory potentials. Multifocal ERG showed abnormalities that sometimes correlated with the visual field appearance and confirmed that the deficit occurs at the retinal level. CONCLUSION: Marked visual field constriction appears to be associated with vigabatrin therapy. The field defects and some electrophysiological abnormalities persist when vigabatrin therapy is withdrawn."],"offsets":[[169,1680]]}],"entities":[{"id":"9716","type":"Chemical","text":["vigabatrin"],"offsets":[[120,130]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"9717","type":"Disease","text":["visual field constriction"],"offsets":[[142,167]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"9718","type":"Disease","text":["visual field constriction"],"offsets":[[190,215]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"9719","type":"Chemical","text":["vigabatrin"],"offsets":[[246,256]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"9720","type":"Chemical","text":["vigabatrin"],"offsets":[[383,393]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"9721","type":"Disease","text":["visual field loss"],"offsets":[[405,422]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"9722","type":"Chemical","text":["vigabatrin"],"offsets":[[509,519]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"9723","type":"Disease","text":["visual field constriction"],"offsets":[[884,909]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"9724","type":"Disease","text":["visual field constriction"],"offsets":[[1497,1522]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"9725","type":"Chemical","text":["vigabatrin"],"offsets":[[1553,1563]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]},{"id":"9726","type":"Chemical","text":["vigabatrin"],"offsets":[[1648,1658]],"normalized":[{"db_name":"MESH","db_id":"D020888"}]}],"events":[],"coreferences":[],"relations":[{"id":"9727","type":"CID","arg1_id":"9716","arg2_id":"9717","normalized":[]},{"id":"9728","type":"CID","arg1_id":"9716","arg2_id":"9718","normalized":[]},{"id":"9729","type":"CID","arg1_id":"9716","arg2_id":"9721","normalized":[]},{"id":"9730","type":"CID","arg1_id":"9716","arg2_id":"9723","normalized":[]},{"id":"9731","type":"CID","arg1_id":"9716","arg2_id":"9724","normalized":[]},{"id":"9732","type":"CID","arg1_id":"9719","arg2_id":"9717","normalized":[]},{"id":"9733","type":"CID","arg1_id":"9719","arg2_id":"9718","normalized":[]},{"id":"9734","type":"CID","arg1_id":"9719","arg2_id":"9721","normalized":[]},{"id":"9735","type":"CID","arg1_id":"9719","arg2_id":"9723","normalized":[]},{"id":"9736","type":"CID","arg1_id":"9719","arg2_id":"9724","normalized":[]},{"id":"9737","type":"CID","arg1_id":"9720","arg2_id":"9717","normalized":[]},{"id":"9738","type":"CID","arg1_id":"9720","arg2_id":"9718","normalized":[]},{"id":"9739","type":"CID","arg1_id":"9720","arg2_id":"9721","normalized":[]},{"id":"9740","type":"CID","arg1_id":"9720","arg2_id":"9723","normalized":[]},{"id":"9741","type":"CID","arg1_id":"9720","arg2_id":"9724","normalized":[]},{"id":"9742","type":"CID","arg1_id":"9722","arg2_id":"9717","normalized":[]},{"id":"9743","type":"CID","arg1_id":"9722","arg2_id":"9718","normalized":[]},{"id":"9744","type":"CID","arg1_id":"9722","arg2_id":"9721","normalized":[]},{"id":"9745","type":"CID","arg1_id":"9722","arg2_id":"9723","normalized":[]},{"id":"9746","type":"CID","arg1_id":"9722","arg2_id":"9724","normalized":[]},{"id":"9747","type":"CID","arg1_id":"9725","arg2_id":"9717","normalized":[]},{"id":"9748","type":"CID","arg1_id":"9725","arg2_id":"9718","normalized":[]},{"id":"9749","type":"CID","arg1_id":"9725","arg2_id":"9721","normalized":[]},{"id":"9750","type":"CID","arg1_id":"9725","arg2_id":"9723","normalized":[]},{"id":"9751","type":"CID","arg1_id":"9725","arg2_id":"9724","normalized":[]},{"id":"9752","type":"CID","arg1_id":"9726","arg2_id":"9717","normalized":[]},{"id":"9753","type":"CID","arg1_id":"9726","arg2_id":"9718","normalized":[]},{"id":"9754","type":"CID","arg1_id":"9726","arg2_id":"9721","normalized":[]},{"id":"9755","type":"CID","arg1_id":"9726","arg2_id":"9723","normalized":[]},{"id":"9756","type":"CID","arg1_id":"9726","arg2_id":"9724","normalized":[]}]}
{"id":"9757","document_id":"11063349","passages":[{"id":"9758","type":"title","text":["Conversion to rapamycin immunosuppression in renal transplant recipients: report of an initial experience."],"offsets":[[0,106]]},{"id":"9759","type":"abstract","text":["BACKGROUND: The aim of this study is to evaluate the effects of RAPA conversion in patients undergoing cyclosporine (CsA) or tacrolimus (Tac) toxicity. METHODS: Twenty renal transplant recipients were switched to fixed dose rapamycin (RAPA) (5 mg\/day) 0 to 204 months posttransplant. Drug monitoring was not initially used to adjust doses. The indications for switch were chronic CsA or Tac nephrotoxicity (12), acute CsA or Tac toxicity (3), severe facial dysmorphism (2), posttransplant lymphoproliferative disorder (PTLD) in remission (2), and hepatotoxicity in 1. Follow-up is 7 to 24 months. RESULTS: In the 12 patients switched because of chronic nephrotoxicity there was a significant decrease in serum creatinine [233+\/-34 to 210+\/-56 micromol\/liter (P<0.05) at 6 months]. Facial dysmorphism improved in two patients. No relapse of PTLD was observed. Five patients developed pneumonia (two Pneumocystis carinii pneumonia, one infectious mononucleosis with polyclonal PTLD lung infiltrate) and two had bronchiolitis obliterans. There were no deaths. RAPA was discontinued in four patients, because of pneumonia in two, PTLD in one, and oral aphtous ulcers in one. RAPA levels were high (>15 ng\/ml) in 7 of 13 (54%) patients. CONCLUSIONS: RAPA conversion provides adequate immunosuppression to enable CsA withdrawal. However, when converting patients to RAPA drug levels should be monitored to avoid over-immunosuppression and adequate antiviral and Pneumocystis carinii pneumonia prophylaxis should be given."],"offsets":[[107,1622]]}],"entities":[{"id":"9760","type":"Chemical","text":["rapamycin"],"offsets":[[14,23]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"9761","type":"Chemical","text":["RAPA"],"offsets":[[171,175]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"9762","type":"Chemical","text":["cyclosporine"],"offsets":[[210,222]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"9763","type":"Chemical","text":["CsA"],"offsets":[[224,227]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"9764","type":"Chemical","text":["tacrolimus"],"offsets":[[232,242]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"9765","type":"Chemical","text":["Tac"],"offsets":[[244,247]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"9766","type":"Disease","text":["toxicity"],"offsets":[[249,257]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"9767","type":"Chemical","text":["rapamycin"],"offsets":[[331,340]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"9768","type":"Chemical","text":["RAPA"],"offsets":[[342,346]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"9769","type":"Chemical","text":["CsA"],"offsets":[[487,490]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"9770","type":"Chemical","text":["Tac"],"offsets":[[494,497]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"9771","type":"Disease","text":["nephrotoxicity"],"offsets":[[498,512]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"9772","type":"Chemical","text":["CsA"],"offsets":[[525,528]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"9773","type":"Chemical","text":["Tac"],"offsets":[[532,535]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"9774","type":"Disease","text":["toxicity"],"offsets":[[536,544]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"9775","type":"Disease","text":["facial dysmorphism"],"offsets":[[557,575]],"normalized":[]},{"id":"9776","type":"Disease","text":["posttransplant lymphoproliferative disorder"],"offsets":[[581,624]],"normalized":[{"db_name":"MESH","db_id":"D008232"}]},{"id":"9777","type":"Disease","text":["PTLD"],"offsets":[[626,630]],"normalized":[{"db_name":"MESH","db_id":"D008232"}]},{"id":"9778","type":"Disease","text":["hepatotoxicity"],"offsets":[[654,668]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"9779","type":"Disease","text":["nephrotoxicity"],"offsets":[[760,774]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"9780","type":"Chemical","text":["creatinine"],"offsets":[[817,827]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"9781","type":"Disease","text":["Facial dysmorphism"],"offsets":[[888,906]],"normalized":[]},{"id":"9782","type":"Disease","text":["PTLD"],"offsets":[[947,951]],"normalized":[{"db_name":"MESH","db_id":"D008232"}]},{"id":"9783","type":"Disease","text":["pneumonia"],"offsets":[[990,999]],"normalized":[{"db_name":"MESH","db_id":"D011014"}]},{"id":"9784","type":"Disease","text":["Pneumocystis carinii pneumonia"],"offsets":[[1005,1035]],"normalized":[{"db_name":"MESH","db_id":"D011020"}]},{"id":"9785","type":"Disease","text":["infectious mononucleosis"],"offsets":[[1041,1065]],"normalized":[{"db_name":"MESH","db_id":"D007244"}]},{"id":"9786","type":"Disease","text":["PTLD"],"offsets":[[1082,1086]],"normalized":[{"db_name":"MESH","db_id":"D008232"}]},{"id":"9787","type":"Disease","text":["bronchiolitis obliterans"],"offsets":[[1116,1140]],"normalized":[{"db_name":"MESH","db_id":"D001989"}]},{"id":"9788","type":"Chemical","text":["RAPA"],"offsets":[[1164,1168]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"9789","type":"Disease","text":["pneumonia"],"offsets":[[1215,1224]],"normalized":[{"db_name":"MESH","db_id":"D011014"}]},{"id":"9790","type":"Disease","text":["PTLD"],"offsets":[[1233,1237]],"normalized":[{"db_name":"MESH","db_id":"D008232"}]},{"id":"9791","type":"Disease","text":["aphtous ulcers"],"offsets":[[1255,1269]],"normalized":[{"db_name":"MESH","db_id":"D013281"}]},{"id":"9792","type":"Chemical","text":["RAPA"],"offsets":[[1278,1282]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"9793","type":"Chemical","text":["RAPA"],"offsets":[[1352,1356]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"9794","type":"Chemical","text":["CsA"],"offsets":[[1414,1417]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"9795","type":"Chemical","text":["RAPA"],"offsets":[[1467,1471]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"9796","type":"Disease","text":["Pneumocystis carinii pneumonia"],"offsets":[[1563,1593]],"normalized":[{"db_name":"MESH","db_id":"D011020"}]}],"events":[],"coreferences":[],"relations":[{"id":"9797","type":"CID","arg1_id":"9764","arg2_id":"9771","normalized":[]},{"id":"9798","type":"CID","arg1_id":"9764","arg2_id":"9779","normalized":[]},{"id":"9799","type":"CID","arg1_id":"9765","arg2_id":"9771","normalized":[]},{"id":"9800","type":"CID","arg1_id":"9765","arg2_id":"9779","normalized":[]},{"id":"9801","type":"CID","arg1_id":"9770","arg2_id":"9771","normalized":[]},{"id":"9802","type":"CID","arg1_id":"9770","arg2_id":"9779","normalized":[]},{"id":"9803","type":"CID","arg1_id":"9773","arg2_id":"9771","normalized":[]},{"id":"9804","type":"CID","arg1_id":"9773","arg2_id":"9779","normalized":[]},{"id":"9805","type":"CID","arg1_id":"9762","arg2_id":"9771","normalized":[]},{"id":"9806","type":"CID","arg1_id":"9762","arg2_id":"9779","normalized":[]},{"id":"9807","type":"CID","arg1_id":"9763","arg2_id":"9771","normalized":[]},{"id":"9808","type":"CID","arg1_id":"9763","arg2_id":"9779","normalized":[]},{"id":"9809","type":"CID","arg1_id":"9769","arg2_id":"9771","normalized":[]},{"id":"9810","type":"CID","arg1_id":"9769","arg2_id":"9779","normalized":[]},{"id":"9811","type":"CID","arg1_id":"9772","arg2_id":"9771","normalized":[]},{"id":"9812","type":"CID","arg1_id":"9772","arg2_id":"9779","normalized":[]},{"id":"9813","type":"CID","arg1_id":"9794","arg2_id":"9771","normalized":[]},{"id":"9814","type":"CID","arg1_id":"9794","arg2_id":"9779","normalized":[]}]}
{"id":"9815","document_id":"10091616","passages":[{"id":"9816","type":"title","text":["Worsening of levodopa-induced dyskinesias by motor and mental tasks."],"offsets":[[0,68]]},{"id":"9817","type":"abstract","text":["Ten patients who had Parkinson's disease with disabling dyskinesia were included in this study to evaluate the role of mental (mental calculation) and motor (flexion\/extension of right fingers, flexion\/extension of left fingers, flexion\/extension of the neck, speaking aloud) tasks on the worsening of peak-dose dyskinesia following administration of an effective single dose of apomorphine. Compared with the score at rest (1.3+\/-0.3), a significant aggravation of the dyskinesia score was observed during speaking aloud (5.2+\/-1.1, p<0.05), movements of right (4.5+\/-1.0, p<0.05) and left (3.7+\/-0.8, p<0.05) fingers, movements of the neck (5.1+\/-1.0, p<0.05), and mental calculation (3.1+\/-1.0, p<0.05). These results suggest that activation tasks such as \"speaking aloud\" could be used for objective assessment of dyskinesia severity."],"offsets":[[69,907]]}],"entities":[{"id":"9818","type":"Chemical","text":["levodopa"],"offsets":[[13,21]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"9819","type":"Disease","text":["dyskinesias"],"offsets":[[30,41]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"9820","type":"Disease","text":["Parkinson's disease"],"offsets":[[90,109]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"9821","type":"Disease","text":["dyskinesia"],"offsets":[[125,135]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"9822","type":"Disease","text":["dyskinesia"],"offsets":[[381,391]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"9823","type":"Chemical","text":["apomorphine"],"offsets":[[448,459]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"9824","type":"Disease","text":["dyskinesia"],"offsets":[[539,549]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"9825","type":"Disease","text":["dyskinesia"],"offsets":[[887,897]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]}],"events":[],"coreferences":[],"relations":[{"id":"9826","type":"CID","arg1_id":"9823","arg2_id":"9819","normalized":[]},{"id":"9827","type":"CID","arg1_id":"9823","arg2_id":"9821","normalized":[]},{"id":"9828","type":"CID","arg1_id":"9823","arg2_id":"9822","normalized":[]},{"id":"9829","type":"CID","arg1_id":"9823","arg2_id":"9824","normalized":[]},{"id":"9830","type":"CID","arg1_id":"9823","arg2_id":"9825","normalized":[]},{"id":"9831","type":"CID","arg1_id":"9818","arg2_id":"9819","normalized":[]},{"id":"9832","type":"CID","arg1_id":"9818","arg2_id":"9821","normalized":[]},{"id":"9833","type":"CID","arg1_id":"9818","arg2_id":"9822","normalized":[]},{"id":"9834","type":"CID","arg1_id":"9818","arg2_id":"9824","normalized":[]},{"id":"9835","type":"CID","arg1_id":"9818","arg2_id":"9825","normalized":[]}]}
{"id":"9836","document_id":"9952311","passages":[{"id":"9837","type":"title","text":["Structural and functional impairment of mitochondria in adriamycin-induced cardiomyopathy in mice: suppression of cytochrome c oxidase II gene expression."],"offsets":[[0,154]]},{"id":"9838","type":"abstract","text":["The use of adriamycin (ADR) in cancer chemotherapy has been limited due to its cumulative cardiovascular toxicity. Earlier observations that ADR interacts with mitochondrial cytochrome c oxidase (COX) and suppresses its enzyme activity led us to investigate ADR's action on the cardiovascular functions and heart mitochondrial morphology in Balb-c mice i.p. treated with ADR for several weeks. At various times during treatment, the animals were assessed for cardiovascular functions by electrocardiography and for heart tissue damage by electron microscopy. In parallel, total RNA was extracted from samples of dissected heart and analyzed by Northern blot hybridization to determine the steady-state level of three RNA transcripts encoded by the COXII, COXIII, and COXIV genes. Similarly, samples obtained from the liver of the same animals were analyzed for comparative studies. Our results indicated that 1) treatment of mice with ADR caused cardiovascular arrhythmias characterized by bradycardia, extension of ventricular depolarization time (tQRS), and failure of QRS at high concentrations (10-14 mg\/kg body weight cumulative dose); 2) the heart mitochondria underwent swelling, fusion, dissolution, and\/or disruption of mitochondrial cristae after several weeks of treatment. Such abnormalities were not observed in the mitochondria of liver tissue; and 3) among the three genes of COX enzyme examined, only COXII gene expression was suppressed by ADR treatment, mainly after 8 weeks in both heart and liver. Knowing that heart mitochondria represent almost 40% of heart muscle by weight, we conclude that the deteriorating effects of ADR on cardiovascular function involve mitochondrial structural and functional impairment."],"offsets":[[155,1889]]}],"entities":[{"id":"9839","type":"Disease","text":["Structural and functional impairment of mitochondria"],"offsets":[[0,52]],"normalized":[{"db_name":"MESH","db_id":"D028361"}]},{"id":"9840","type":"Chemical","text":["adriamycin"],"offsets":[[56,66]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"9841","type":"Disease","text":["cardiomyopathy"],"offsets":[[75,89]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"9842","type":"Chemical","text":["adriamycin"],"offsets":[[166,176]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"9843","type":"Chemical","text":["ADR"],"offsets":[[178,181]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"9844","type":"Disease","text":["cancer"],"offsets":[[186,192]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"9845","type":"Disease","text":["cardiovascular toxicity"],"offsets":[[245,268]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"9846","type":"Chemical","text":["ADR"],"offsets":[[296,299]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"9847","type":"Chemical","text":["ADR"],"offsets":[[413,416]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"9848","type":"Chemical","text":["ADR"],"offsets":[[526,529]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"9849","type":"Chemical","text":["ADR"],"offsets":[[1090,1093]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"9850","type":"Disease","text":["cardiovascular arrhythmias"],"offsets":[[1101,1127]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"9851","type":"Disease","text":["bradycardia"],"offsets":[[1145,1156]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"9852","type":"Disease","text":["swelling"],"offsets":[[1332,1340]],"normalized":[{"db_name":"MESH","db_id":"D004487"}]},{"id":"9853","type":"Chemical","text":["ADR"],"offsets":[[1612,1615]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"9854","type":"Chemical","text":["ADR"],"offsets":[[1799,1802]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"9855","type":"Disease","text":["mitochondrial structural and functional impairment"],"offsets":[[1838,1888]],"normalized":[{"db_name":"MESH","db_id":"D028361"}]}],"events":[],"coreferences":[],"relations":[{"id":"9856","type":"CID","arg1_id":"9840","arg2_id":"9839","normalized":[]},{"id":"9857","type":"CID","arg1_id":"9840","arg2_id":"9855","normalized":[]},{"id":"9858","type":"CID","arg1_id":"9842","arg2_id":"9839","normalized":[]},{"id":"9859","type":"CID","arg1_id":"9842","arg2_id":"9855","normalized":[]},{"id":"9860","type":"CID","arg1_id":"9843","arg2_id":"9839","normalized":[]},{"id":"9861","type":"CID","arg1_id":"9843","arg2_id":"9855","normalized":[]},{"id":"9862","type":"CID","arg1_id":"9846","arg2_id":"9839","normalized":[]},{"id":"9863","type":"CID","arg1_id":"9846","arg2_id":"9855","normalized":[]},{"id":"9864","type":"CID","arg1_id":"9847","arg2_id":"9839","normalized":[]},{"id":"9865","type":"CID","arg1_id":"9847","arg2_id":"9855","normalized":[]},{"id":"9866","type":"CID","arg1_id":"9848","arg2_id":"9839","normalized":[]},{"id":"9867","type":"CID","arg1_id":"9848","arg2_id":"9855","normalized":[]},{"id":"9868","type":"CID","arg1_id":"9849","arg2_id":"9839","normalized":[]},{"id":"9869","type":"CID","arg1_id":"9849","arg2_id":"9855","normalized":[]},{"id":"9870","type":"CID","arg1_id":"9853","arg2_id":"9839","normalized":[]},{"id":"9871","type":"CID","arg1_id":"9853","arg2_id":"9855","normalized":[]},{"id":"9872","type":"CID","arg1_id":"9854","arg2_id":"9839","normalized":[]},{"id":"9873","type":"CID","arg1_id":"9854","arg2_id":"9855","normalized":[]},{"id":"9874","type":"CID","arg1_id":"9840","arg2_id":"9851","normalized":[]},{"id":"9875","type":"CID","arg1_id":"9842","arg2_id":"9851","normalized":[]},{"id":"9876","type":"CID","arg1_id":"9843","arg2_id":"9851","normalized":[]},{"id":"9877","type":"CID","arg1_id":"9846","arg2_id":"9851","normalized":[]},{"id":"9878","type":"CID","arg1_id":"9847","arg2_id":"9851","normalized":[]},{"id":"9879","type":"CID","arg1_id":"9848","arg2_id":"9851","normalized":[]},{"id":"9880","type":"CID","arg1_id":"9849","arg2_id":"9851","normalized":[]},{"id":"9881","type":"CID","arg1_id":"9853","arg2_id":"9851","normalized":[]},{"id":"9882","type":"CID","arg1_id":"9854","arg2_id":"9851","normalized":[]}]}
{"id":"9883","document_id":"9915601","passages":[{"id":"9884","type":"title","text":["Enhanced bradycardia induced by beta-adrenoceptor antagonists in rats pretreated with isoniazid."],"offsets":[[0,96]]},{"id":"9885","type":"abstract","text":["High doses of isoniazid increase hypotension induced by vasodilators and change the accompanying reflex tachycardia to bradycardia, an interaction attributed to decreased synthesis of brain gamma-aminobutyric acid (GABA). In the present study, the possible enhancement by isoniazid of bradycardia induced by beta-adrenoceptor antagonists was determined in rats anaesthetised with chloralose-urethane. Isoniazid significantly increased bradycardia after propranolol, pindolol, labetalol and atenolol, as well as after clonidine, but not after hexamethonium or carbachol. Enhancement was not observed in rats pretreated with methylatropine or previously vagotomised. These results are compatible with interference by isoniazid with GABAergic inhibition of cardiac parasympathetic tone. Such interference could be exerted centrally, possibly at the nucleus ambiguus, or peripherally at the sinus node."],"offsets":[[97,995]]}],"entities":[{"id":"9886","type":"Disease","text":["bradycardia"],"offsets":[[9,20]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"9887","type":"Chemical","text":["isoniazid"],"offsets":[[86,95]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]},{"id":"9888","type":"Chemical","text":["isoniazid"],"offsets":[[111,120]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]},{"id":"9889","type":"Disease","text":["hypotension"],"offsets":[[130,141]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"9890","type":"Disease","text":["tachycardia"],"offsets":[[201,212]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]},{"id":"9891","type":"Disease","text":["bradycardia"],"offsets":[[216,227]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"9892","type":"Chemical","text":["gamma-aminobutyric acid"],"offsets":[[287,310]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"9893","type":"Chemical","text":["GABA"],"offsets":[[312,316]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"9894","type":"Chemical","text":["isoniazid"],"offsets":[[369,378]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]},{"id":"9895","type":"Disease","text":["bradycardia"],"offsets":[[382,393]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"9896","type":"Chemical","text":["chloralose"],"offsets":[[477,487]],"normalized":[{"db_name":"MESH","db_id":"D002698"}]},{"id":"9897","type":"Chemical","text":["urethane"],"offsets":[[488,496]],"normalized":[{"db_name":"MESH","db_id":"D014520"}]},{"id":"9898","type":"Chemical","text":["Isoniazid"],"offsets":[[498,507]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]},{"id":"9899","type":"Disease","text":["bradycardia"],"offsets":[[532,543]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"9900","type":"Chemical","text":["propranolol"],"offsets":[[550,561]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"9901","type":"Chemical","text":["pindolol"],"offsets":[[563,571]],"normalized":[{"db_name":"MESH","db_id":"D010869"}]},{"id":"9902","type":"Chemical","text":["labetalol"],"offsets":[[573,582]],"normalized":[{"db_name":"MESH","db_id":"D007741"}]},{"id":"9903","type":"Chemical","text":["atenolol"],"offsets":[[587,595]],"normalized":[{"db_name":"MESH","db_id":"D001262"}]},{"id":"9904","type":"Chemical","text":["clonidine"],"offsets":[[614,623]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"9905","type":"Chemical","text":["hexamethonium"],"offsets":[[639,652]],"normalized":[{"db_name":"MESH","db_id":"D018738"}]},{"id":"9906","type":"Chemical","text":["carbachol"],"offsets":[[656,665]],"normalized":[{"db_name":"MESH","db_id":"D002217"}]},{"id":"9907","type":"Chemical","text":["methylatropine"],"offsets":[[720,734]],"normalized":[{"db_name":"MESH","db_id":"C006649"}]},{"id":"9908","type":"Chemical","text":["isoniazid"],"offsets":[[812,821]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]}],"events":[],"coreferences":[],"relations":[{"id":"9909","type":"CID","arg1_id":"9887","arg2_id":"9886","normalized":[]},{"id":"9910","type":"CID","arg1_id":"9887","arg2_id":"9891","normalized":[]},{"id":"9911","type":"CID","arg1_id":"9887","arg2_id":"9895","normalized":[]},{"id":"9912","type":"CID","arg1_id":"9887","arg2_id":"9899","normalized":[]},{"id":"9913","type":"CID","arg1_id":"9888","arg2_id":"9886","normalized":[]},{"id":"9914","type":"CID","arg1_id":"9888","arg2_id":"9891","normalized":[]},{"id":"9915","type":"CID","arg1_id":"9888","arg2_id":"9895","normalized":[]},{"id":"9916","type":"CID","arg1_id":"9888","arg2_id":"9899","normalized":[]},{"id":"9917","type":"CID","arg1_id":"9894","arg2_id":"9886","normalized":[]},{"id":"9918","type":"CID","arg1_id":"9894","arg2_id":"9891","normalized":[]},{"id":"9919","type":"CID","arg1_id":"9894","arg2_id":"9895","normalized":[]},{"id":"9920","type":"CID","arg1_id":"9894","arg2_id":"9899","normalized":[]},{"id":"9921","type":"CID","arg1_id":"9898","arg2_id":"9886","normalized":[]},{"id":"9922","type":"CID","arg1_id":"9898","arg2_id":"9891","normalized":[]},{"id":"9923","type":"CID","arg1_id":"9898","arg2_id":"9895","normalized":[]},{"id":"9924","type":"CID","arg1_id":"9898","arg2_id":"9899","normalized":[]},{"id":"9925","type":"CID","arg1_id":"9908","arg2_id":"9886","normalized":[]},{"id":"9926","type":"CID","arg1_id":"9908","arg2_id":"9891","normalized":[]},{"id":"9927","type":"CID","arg1_id":"9908","arg2_id":"9895","normalized":[]},{"id":"9928","type":"CID","arg1_id":"9908","arg2_id":"9899","normalized":[]},{"id":"9929","type":"CID","arg1_id":"9887","arg2_id":"9889","normalized":[]},{"id":"9930","type":"CID","arg1_id":"9888","arg2_id":"9889","normalized":[]},{"id":"9931","type":"CID","arg1_id":"9894","arg2_id":"9889","normalized":[]},{"id":"9932","type":"CID","arg1_id":"9898","arg2_id":"9889","normalized":[]},{"id":"9933","type":"CID","arg1_id":"9908","arg2_id":"9889","normalized":[]}]}
{"id":"9934","document_id":"9758264","passages":[{"id":"9935","type":"title","text":["Epileptogenic activity of folic acid after drug induces SLE (folic acid and epilepsy)"],"offsets":[[0,85]]},{"id":"9936","type":"abstract","text":["OBJECTIVE: To study the effect of folic acid-containing multivitamin supplementation in epileptic women before and during pregnancy in order to determine the rate of structural birth defects and epilepsy-related side effects. STUDY DESIGN: First a randomised trial, later periconception care including in total 12225 females. RESULTS: Of 60 epileptic women with periconceptional folic acid (0.8 mg)-containing multivitamin supplementation, no one developed epilepsy-related side effects during the periconception period. One epileptic woman delivered a newborn with cleft lip and palate. Another patient exhibited with a cluster of seizures after the periconception period using another multivitamin. This 22-year-old epileptic woman was treated continuously by carbamazepine and a folic acid (1 mg)-containing multivitamin from the 20th week of gestation. She developed status epilepticus and later symptoms of systemic lupus erythematodes. Her pregnancy ended with stillbirth. CONCLUSIONS: The epileptic pregnant patient's autoimmune disease (probably drug-induced lupus) could damage the blood-brain barrier, therefore the therapeutic dose (> or =1 mg) of folic acid triggered a cluster of seizures. Physiological dose (<1 mg) of folic acid both in healthy and 60 epileptic women, all without any autoimmune disease, did not increase the risk for epileptic seizures."],"offsets":[[86,1455]]}],"entities":[{"id":"9937","type":"Chemical","text":["folic acid"],"offsets":[[26,36]],"normalized":[{"db_name":"MESH","db_id":"D005492"}]},{"id":"9938","type":"Disease","text":["SLE"],"offsets":[[56,59]],"normalized":[{"db_name":"MESH","db_id":"D008180"}]},{"id":"9939","type":"Chemical","text":["folic acid"],"offsets":[[61,71]],"normalized":[{"db_name":"MESH","db_id":"D005492"}]},{"id":"9940","type":"Disease","text":["epilepsy"],"offsets":[[76,84]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"9941","type":"Chemical","text":["folic acid"],"offsets":[[120,130]],"normalized":[{"db_name":"MESH","db_id":"D005492"}]},{"id":"9942","type":"Disease","text":["epileptic"],"offsets":[[174,183]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"9943","type":"Disease","text":["birth defects"],"offsets":[[263,276]],"normalized":[{"db_name":"MESH","db_id":"D000014"}]},{"id":"9944","type":"Disease","text":["epilepsy"],"offsets":[[281,289]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"9945","type":"Disease","text":["epileptic"],"offsets":[[427,436]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"9946","type":"Chemical","text":["folic acid"],"offsets":[[465,475]],"normalized":[{"db_name":"MESH","db_id":"D005492"}]},{"id":"9947","type":"Disease","text":["epilepsy"],"offsets":[[543,551]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"9948","type":"Disease","text":["epileptic"],"offsets":[[611,620]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"9949","type":"Disease","text":["cleft lip and palate"],"offsets":[[652,672]],"normalized":[{"db_name":"MESH","db_id":"D002971"},{"db_name":"MESH","db_id":"D002972"}]},{"id":"9950","type":"Disease","text":["cleft lip"],"offsets":[[652,661]],"normalized":[{"db_name":"MESH","db_id":"D002971"}]},{"id":"9951","type":"Disease","text":["cleft","palate"],"offsets":[[652,657],[666,672]],"normalized":[{"db_name":"MESH","db_id":"D002972"}]},{"id":"9952","type":"Disease","text":["seizures"],"offsets":[[718,726]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"9953","type":"Disease","text":["epileptic"],"offsets":[[804,813]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"9954","type":"Chemical","text":["carbamazepine"],"offsets":[[848,861]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"9955","type":"Chemical","text":["folic acid"],"offsets":[[868,878]],"normalized":[{"db_name":"MESH","db_id":"D005492"}]},{"id":"9956","type":"Disease","text":["status epilepticus"],"offsets":[[957,975]],"normalized":[{"db_name":"MESH","db_id":"D013226"}]},{"id":"9957","type":"Disease","text":["systemic lupus 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{"id":"10003","document_id":"9669632","passages":[{"id":"10004","type":"title","text":["Effects of cisapride on symptoms and postcibal small-bowel motor function in patients with irritable bowel syndrome."],"offsets":[[0,116]]},{"id":"10005","type":"abstract","text":["BACKGROUND: Irritable bowel syndrome is a common cause of abdominal pain and discomfort and may be related to disordered gastrointestinal motility. Our aim was to assess the effects of long-term treatment with a prokinetic agent, cisapride, on postprandial jejunal motility and symptoms in the irritable bowel syndrome (IBS). METHODS: Thirty-eight patients with IBS (constipation-predominant, n = 17; diarrhoea-predominant, n = 21) underwent 24-h ambulatory jejunal manometry before and after 12 week's treatment [cisapride, 5 mg three times daily (n = 19) or placebo (n = 19)]. RESULTS: In diarrhoea-predominant patients significant differences in contraction characteristics were observed between the cisapride and placebo groups. In cisapride-treated diarrhoea-predominant patients the mean contraction amplitude was higher (29.3 +\/- 3.2 versus 24.9 +\/- 2.6 mm Hg, cisapride versus placebo (P < 0.001); pretreatment, 25.7 +\/- 6.0 mm Hg), the mean contraction duration longer (3.4 +\/- 0.2 versus 3.0 +\/- 0.2 sec, cisapride versus placebo (P < 0.001); pretreatment, 3.1 +\/- 0.5 sec), and the mean contraction frequency lower (2.0 +\/- 0.2 versus 2.5 +\/- 0.4 cont.\/min, cisapride versus placebo (P < 0.001); pretreatment, 2.5 +\/- 1.1 cont.\/min] than patients treated with placebo. No significant differences in jejunal motility were found in the constipation-predominant IBS group. Symptoms were assessed by using a visual analogue scale before and after treatment. Symptom scores relating to the severity of constipation were lower in cisapride-treated constipation-predominant IBS patients [score, 54 +\/- 5 versus 67 +\/- 14 mm, cisapride versus placebo (P < 0.05); pretreatment, 62 +\/- 19 mm]. Diarrhoea-predominant IBS patients had a higher pain score after cisapride therapy [score, 55 +\/- 15 versus 34 +\/- 12 mm, cisapride versus placebo (P < 0.05); pretreatment, 67 +\/- 19 mm]. CONCLUSION: Cisapride affects jejunal contraction characteristics and some symptoms in IBS."],"offsets":[[117,2091]]}],"entities":[{"id":"10006","type":"Chemical","text":["cisapride"],"offsets":[[11,20]],"normalized":[{"db_name":"MESH","db_id":"D020117"}]},{"id":"10007","type":"Disease","text":["irritable bowel syndrome"],"offsets":[[91,115]],"normalized":[{"db_name":"MESH","db_id":"D043183"}]},{"id":"10008","type":"Disease","text":["Irritable bowel syndrome"],"offsets":[[129,153]],"normalized":[{"db_name":"MESH","db_id":"D043183"}]},{"id":"10009","type":"Disease","text":["abdominal pain"],"offsets":[[175,189]],"normalized":[{"db_name":"MESH","db_id":"D015746"}]},{"id":"10010","type":"Disease","text":["disordered gastrointestinal motility"],"offsets":[[227,263]],"normalized":[{"db_name":"MESH","db_id":"D005767"}]},{"id":"10011","type":"Chemical","text":["cisapride"],"offsets":[[347,356]],"normalized":[{"db_name":"MESH","db_id":"D020117"}]},{"id":"10012","type":"Disease","text":["irritable bowel 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{"id":"10052","document_id":"9326871","passages":[{"id":"10053","type":"title","text":["Clarithromycin-induced ventricular tachycardia."],"offsets":[[0,47]]},{"id":"10054","type":"abstract","text":["Clarithromycin is a relatively new macrolide antibiotic that offers twice-daily dosing. It differs from erythromycin only in the methylation of the hydroxyl group at position 6. Although the side-effect profile of erythromycin is established, including gastroenteritis and interactions with other drugs subject to hepatic mixed-function oxidase metabolism, experience with the newer macrolides is still being recorded. Cardiotoxicity has been demonstrated after both intravenous and oral administration of erythromycin but has never been reported with the newer macrolides. We report a case of ventricular dysrhythmias that occurred after six therapeutic doses of clarithromycin. The dysrhythmias resolved after discontinuation of the drug."],"offsets":[[48,788]]}],"entities":[{"id":"10055","type":"Chemical","text":["Clarithromycin"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D017291"}]},{"id":"10056","type":"Disease","text":["ventricular tachycardia"],"offsets":[[23,46]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"10057","type":"Chemical","text":["Clarithromycin"],"offsets":[[48,62]],"normalized":[{"db_name":"MESH","db_id":"D017291"}]},{"id":"10058","type":"Chemical","text":["macrolide"],"offsets":[[83,92]],"normalized":[{"db_name":"MESH","db_id":"D018942"}]},{"id":"10059","type":"Chemical","text":["erythromycin"],"offsets":[[152,164]],"normalized":[{"db_name":"MESH","db_id":"D004917"}]},{"id":"10060","type":"Chemical","text":["erythromycin"],"offsets":[[262,274]],"normalized":[{"db_name":"MESH","db_id":"D004917"}]},{"id":"10061","type":"Disease","text":["gastroenteritis"],"offsets":[[301,316]],"normalized":[{"db_name":"MESH","db_id":"D005759"}]},{"id":"10062","type":"Chemical","text":["macrolides"],"offsets":[[431,441]],"normalized":[{"db_name":"MESH","db_id":"D018942"}]},{"id":"10063","type":"Disease","text":["Cardiotoxicity"],"offsets":[[467,481]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"10064","type":"Chemical","text":["erythromycin"],"offsets":[[554,566]],"normalized":[{"db_name":"MESH","db_id":"D004917"}]},{"id":"10065","type":"Chemical","text":["macrolides"],"offsets":[[610,620]],"normalized":[{"db_name":"MESH","db_id":"D018942"}]},{"id":"10066","type":"Disease","text":["ventricular dysrhythmias"],"offsets":[[642,666]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"10067","type":"Chemical","text":["clarithromycin"],"offsets":[[712,726]],"normalized":[{"db_name":"MESH","db_id":"D017291"}]},{"id":"10068","type":"Disease","text":["dysrhythmias"],"offsets":[[732,744]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]}],"events":[],"coreferences":[],"relations":[{"id":"10069","type":"CID","arg1_id":"10059","arg2_id":"10061","normalized":[]},{"id":"10070","type":"CID","arg1_id":"10060","arg2_id":"10061","normalized":[]},{"id":"10071","type":"CID","arg1_id":"10064","arg2_id":"10061","normalized":[]},{"id":"10072","type":"CID","arg1_id":"10055","arg2_id":"10056","normalized":[]},{"id":"10073","type":"CID","arg1_id":"10057","arg2_id":"10056","normalized":[]},{"id":"10074","type":"CID","arg1_id":"10067","arg2_id":"10056","normalized":[]}]}
{"id":"10075","document_id":"9226773","passages":[{"id":"10076","type":"title","text":["Persistent nephrogenic diabetes insipidus following lithium therapy."],"offsets":[[0,68]]},{"id":"10077","type":"abstract","text":["We report the case of a patient who developed severe hypernatraemic dehydration following a head injury. Ten years previously he had been diagnosed to have lithium-induced nephrogenic diabetes insipidus, and lithium therapy had been discontinued. He remained thirsty and polyuric despite cessation of lithium and investigations on admission showed him to have normal osmoregulated thirst and vasopressin secretion, with clear evidence of nephrogenic diabetes insipidus. Lithium induced nephrogenic diabetes insipidus is considered to be reversible on cessation of therapy but polyuria persisted in this patient for ten years after lithium was stopped. We discuss the possible renal mechanisms and the implications for management of patients with lithium-induced nephrogenic diabetes insipidus."],"offsets":[[69,862]]}],"entities":[{"id":"10078","type":"Disease","text":["nephrogenic diabetes insipidus"],"offsets":[[11,41]],"normalized":[{"db_name":"MESH","db_id":"D018500"}]},{"id":"10079","type":"Chemical","text":["lithium"],"offsets":[[52,59]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"10080","type":"Disease","text":["dehydration"],"offsets":[[137,148]],"normalized":[{"db_name":"MESH","db_id":"D003681"}]},{"id":"10081","type":"Disease","text":["head injury"],"offsets":[[161,172]],"normalized":[{"db_name":"MESH","db_id":"D006259"}]},{"id":"10082","type":"Chemical","text":["lithium"],"offsets":[[225,232]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"10083","type":"Disease","text":["nephrogenic diabetes insipidus"],"offsets":[[241,271]],"normalized":[{"db_name":"MESH","db_id":"D018500"}]},{"id":"10084","type":"Chemical","text":["lithium"],"offsets":[[277,284]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"10085","type":"Disease","text":["polyuric"],"offsets":[[340,348]],"normalized":[{"db_name":"MESH","db_id":"D011141"}]},{"id":"10086","type":"Chemical","text":["lithium"],"offsets":[[370,377]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"10087","type":"Chemical","text":["vasopressin"],"offsets":[[461,472]],"normalized":[{"db_name":"MESH","db_id":"D014667"}]},{"id":"10088","type":"Disease","text":["nephrogenic diabetes insipidus"],"offsets":[[507,537]],"normalized":[{"db_name":"MESH","db_id":"D018500"}]},{"id":"10089","type":"Chemical","text":["Lithium"],"offsets":[[539,546]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"10090","type":"Disease","text":["nephrogenic diabetes 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{"id":"10144","document_id":"8600333","passages":[{"id":"10145","type":"title","text":["Late cardiotoxicity after treatment for a malignant bone tumor."],"offsets":[[0,63]]},{"id":"10146","type":"abstract","text":["Cardiac function was assessed in long-term survivors of malignant bone tumors who were treated according to Rosen's T5 or T10 protocol, both including doxorubicin. Thirty-one patients, age 10-45 years (median age 17.8 years) were evaluated 2.3-14.1 years (median 8.9 years) following completion of treatment. Cumulative doses of doxorubicin were 225-550 mg\/m2 (median dose 360). The evaluation consisted of a history, physical examination, electrocardiogram (ECG), signal averaged ECG, 24-hour ambulatory ECG, echocardiography and radionuclide angiography. Eighteen of 31 (58%) patients showed cardiac toxicity, defined as having one or more of the following abnormalities: late potentials, complex ventricular arrhythmias, left ventricular dilation, decreased shortening fraction, or decreased ejection fraction. The incidence of cardiac abnormalities increased with length of follow-up (P< or = .05). No correlation could be demonstrated between cumulative dose of doxorubicin and cardiac status, except for heart rate variability. When adjusted to body surface area, the left ventricular posterior wall thickness (LVPW index) was decreased in all patients. The incidence of doxorubicin-induced cardiotoxicity is high and increases with follow-up, irrespective of cumulative dose. Life-long cardiac follow-up in these patients is warranted. The results of our study suggest that heart rate variability and LVPW index could be sensitive indicators for cardiotoxicity."],"offsets":[[64,1532]]}],"entities":[{"id":"10147","type":"Disease","text":["cardiotoxicity"],"offsets":[[5,19]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"10148","type":"Disease","text":["bone tumor"],"offsets":[[52,62]],"normalized":[{"db_name":"MESH","db_id":"D001859"}]},{"id":"10149","type":"Disease","text":["bone tumors"],"offsets":[[130,141]],"normalized":[{"db_name":"MESH","db_id":"D001859"}]},{"id":"10150","type":"Chemical","text":["Rosen's T5 or T10 protocol"],"offsets":[[172,198]],"normalized":[{"db_name":"MESH","db_id":"C053519"}]},{"id":"10151","type":"Chemical","text":["doxorubicin"],"offsets":[[215,226]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"10152","type":"Chemical","text":["doxorubicin"],"offsets":[[393,404]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"10153","type":"Disease","text":["cardiac toxicity"],"offsets":[[658,674]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"10154","type":"Disease","text":["ventricular arrhythmias"],"offsets":[[763,786]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"10155","type":"Disease","text":["ventricular dilation"],"offsets":[[793,813]],"normalized":[{"db_name":"MESH","db_id":"D002311"}]},{"id":"10156","type":"Disease","text":["cardiac abnormalities"],"offsets":[[895,916]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"10157","type":"Chemical","text":["doxorubicin"],"offsets":[[1031,1042]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"10158","type":"Chemical","text":["doxorubicin"],"offsets":[[1241,1252]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"10159","type":"Disease","text":["cardiotoxicity"],"offsets":[[1261,1275]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"10160","type":"Disease","text":["cardiotoxicity"],"offsets":[[1517,1531]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]}],"events":[],"coreferences":[],"relations":[{"id":"10161","type":"CID","arg1_id":"10151","arg2_id":"10156","normalized":[]},{"id":"10162","type":"CID","arg1_id":"10152","arg2_id":"10156","normalized":[]},{"id":"10163","type":"CID","arg1_id":"10157","arg2_id":"10156","normalized":[]},{"id":"10164","type":"CID","arg1_id":"10158","arg2_id":"10156","normalized":[]}]}
{"id":"10165","document_id":"8514073","passages":[{"id":"10166","type":"title","text":["Venous complications of midazolam versus diazepam."],"offsets":[[0,50]]},{"id":"10167","type":"abstract","text":["Although some studies have suggested fewer venous complications are associated with midazolam than with diazepam for endoscopic procedures, this variable has not been well documented. We prospectively evaluated the incidence of venous complications after intravenous injection of diazepam or midazolam in 122 consecutive patients undergoing colonoscopy and esophagogastroduodenoscopy. Overall, venous complications were more frequent with diazepam (22 of 62 patients) than with midazolam (4 of 60 patients) (p < 0.001). A palpable venous cord was present in 23% (14 of 62) of patients in the diazepam group, compared with 2% (1 of 60 patients) in the midazolam group (p < 0.002). Pain at the injection site occurred in 35% (22 of 62) of patients in the diazepam group compared with 7% (4 of 60 patients) in the midazolam group (p < 0.001). Swelling and warmth at the injection site were not significantly different between the two groups. Smoking, nonsteroidal anti-inflammatory drug use, intravenous catheter site, dwell time of the needle, alcohol use, and pain during the injection had no effect on the incidence of venous complications."],"offsets":[[51,1191]]}],"entities":[{"id":"10168","type":"Disease","text":["Venous complications"],"offsets":[[0,20]],"normalized":[{"db_name":"MESH","db_id":"D014652"}]},{"id":"10169","type":"Chemical","text":["midazolam"],"offsets":[[24,33]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"10170","type":"Chemical","text":["diazepam"],"offsets":[[41,49]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"10171","type":"Disease","text":["venous complications"],"offsets":[[94,114]],"normalized":[{"db_name":"MESH","db_id":"D014652"}]},{"id":"10172","type":"Chemical","text":["midazolam"],"offsets":[[135,144]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"10173","type":"Chemical","text":["diazepam"],"offsets":[[155,163]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"10174","type":"Disease","text":["venous complications"],"offsets":[[279,299]],"normalized":[{"db_name":"MESH","db_id":"D014652"}]},{"id":"10175","type":"Chemical","text":["diazepam"],"offsets":[[331,339]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"10176","type":"Chemical","text":["midazolam"],"offsets":[[343,352]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"10177","type":"Disease","text":["venous complications"],"offsets":[[445,465]],"normalized":[{"db_name":"MESH","db_id":"D014652"}]},{"id":"10178","type":"Chemical","text":["diazepam"],"offsets":[[490,498]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"10179","type":"Chemical","text":["midazolam"],"offsets":[[529,538]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"10180","type":"Chemical","text":["diazepam"],"offsets":[[643,651]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"10181","type":"Chemical","text":["midazolam"],"offsets":[[702,711]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"10182","type":"Disease","text":["Pain"],"offsets":[[731,735]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"10183","type":"Chemical","text":["diazepam"],"offsets":[[804,812]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"10184","type":"Chemical","text":["midazolam"],"offsets":[[862,871]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"10185","type":"Disease","text":["Swelling"],"offsets":[[891,899]],"normalized":[{"db_name":"MESH","db_id":"D004487"}]},{"id":"10186","type":"Chemical","text":["alcohol"],"offsets":[[1093,1100]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"10187","type":"Disease","text":["pain"],"offsets":[[1110,1114]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"10188","type":"Disease","text":["venous 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{"id":"10249","document_id":"8492347","passages":[{"id":"10250","type":"title","text":["Tetany and rhabdomyolysis due to surreptitious furosemide--importance of magnesium supplementation."],"offsets":[[0,99]]},{"id":"10251","type":"abstract","text":["Diuretics may induce hypokalemia, hypocalcemia and hypomagnesemia. While severe hypokalemia may cause muscle weakness, severe hypomagnesemia is associated with muscle spasms and tetany which cannot be corrected by potassium and calcium supplementation alone (1,2). Surreptitious diuretic ingestion has been described, mainly in women who are concerned that they are obese or edematous. Symptomatic hypokalemia has been reported in such patients (3-7) and in one case hypocalcemia was observed (8), but the effects of magnesium depletion were not noted in these patients."],"offsets":[[100,670]]}],"entities":[{"id":"10252","type":"Disease","text":["Tetany"],"offsets":[[0,6]],"normalized":[{"db_name":"MESH","db_id":"D013746"}]},{"id":"10253","type":"Disease","text":["rhabdomyolysis"],"offsets":[[11,25]],"normalized":[{"db_name":"MESH","db_id":"D012206"}]},{"id":"10254","type":"Chemical","text":["furosemide"],"offsets":[[47,57]],"normalized":[{"db_name":"MESH","db_id":"D005665"}]},{"id":"10255","type":"Chemical","text":["magnesium"],"offsets":[[73,82]],"normalized":[{"db_name":"MESH","db_id":"D008274"}]},{"id":"10256","type":"Disease","text":["hypokalemia"],"offsets":[[121,132]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"10257","type":"Disease","text":["hypocalcemia"],"offsets":[[134,146]],"normalized":[{"db_name":"MESH","db_id":"D006996"}]},{"id":"10258","type":"Disease","text":["hypomagnesemia"],"offsets":[[151,165]],"normalized":[{"db_name":"MESH","db_id":"C537153"}]},{"id":"10259","type":"Disease","text":["hypokalemia"],"offsets":[[180,191]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"10260","type":"Disease","text":["muscle weakness"],"offsets":[[202,217]],"normalized":[{"db_name":"MESH","db_id":"D018908"}]},{"id":"10261","type":"Disease","text":["hypomagnesemia"],"offsets":[[226,240]],"normalized":[{"db_name":"MESH","db_id":"C537153"}]},{"id":"10262","type":"Disease","text":["muscle spasms"],"offsets":[[260,273]],"normalized":[{"db_name":"MESH","db_id":"D013035"}]},{"id":"10263","type":"Disease","text":["tetany"],"offsets":[[278,284]],"normalized":[{"db_name":"MESH","db_id":"D013746"}]},{"id":"10264","type":"Chemical","text":["potassium"],"offsets":[[314,323]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"10265","type":"Chemical","text":["calcium"],"offsets":[[328,335]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"10266","type":"Disease","text":["obese"],"offsets":[[466,471]],"normalized":[{"db_name":"MESH","db_id":"D009765"}]},{"id":"10267","type":"Disease","text":["edematous"],"offsets":[[475,484]],"normalized":[{"db_name":"MESH","db_id":"D004487"}]},{"id":"10268","type":"Disease","text":["hypokalemia"],"offsets":[[498,509]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"10269","type":"Disease","text":["hypocalcemia"],"offsets":[[567,579]],"normalized":[{"db_name":"MESH","db_id":"D006996"}]},{"id":"10270","type":"Chemical","text":["magnesium"],"offsets":[[617,626]],"normalized":[{"db_name":"MESH","db_id":"D008274"}]}],"events":[],"coreferences":[],"relations":[{"id":"10271","type":"CID","arg1_id":"10254","arg2_id":"10253","normalized":[]},{"id":"10272","type":"CID","arg1_id":"10254","arg2_id":"10252","normalized":[]},{"id":"10273","type":"CID","arg1_id":"10254","arg2_id":"10263","normalized":[]}]}
{"id":"10274","document_id":"8410199","passages":[{"id":"10275","type":"title","text":["Loss of glutamate decarboxylase mRNA-containing neurons in the rat dentate gyrus following pilocarpine-induced seizures."],"offsets":[[0,120]]},{"id":"10276","type":"abstract","text":["In situ hybridization methods were used to determine if glutamic acid decarboxylase (GAD) mRNA-containing neurons within the hilus of the dentate gyrus are vulnerable to seizure-induced damage in a model of chronic seizures. Sprague-Dawley rats were injected intraperitoneally with pilocarpine, and the hippocampal formation was studied histologically at 1, 2, 4, and 8 week intervals after pilocarpine-induced seizures. In situ hybridization histochemistry, using a digoxigenin-labeled GAD cRNA probe, demonstrated a substantial decrease in the number of GAD mRNA-containing neurons in the hilus of the dentate gyrus in the pilocarpine-treated rats as compared to controls at all time intervals. Additional neuronanatomical studies, including cresyl violet staining, neuronal degeneration methods, and histochemical localization of glial fibrillary acidic protein, suggested that the decrease in the number of GAD mRNA-containing neurons was related to neuronal loss rather than to a decrease in GAD mRNA levels. The loss of GAD mRNA-containing neurons in the hilus contrasted with the relative preservation of labeled putative basket cells along the inner margin of the granule cell layer. Quantitative analyses of labeled neurons in three regions of the dentate gyrus in the 1 and 2 week groups showed statistically significant decreases in the mean number of GAD mRNA-containing neurons in the hilus of both groups of experimental animals. No significant differences were found in the molecular layer or the granule cell layer, which included labeled neurons along the lower margin of the granule cell layer. The results indicate that, in this model, a subpopulation of GAD mRNA-containing neurons within the dentate gyrus is selectively vulnerable to seizure-induced damage. Such differential vulnerability appears to be another indication of the heterogeneity of GABA neurons."],"offsets":[[121,2003]]}],"entities":[{"id":"10277","type":"Chemical","text":["glutamate"],"offsets":[[8,17]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"10278","type":"Chemical","text":["pilocarpine"],"offsets":[[91,102]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"10279","type":"Disease","text":["seizures"],"offsets":[[111,119]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"10280","type":"Chemical","text":["glutamic acid"],"offsets":[[177,190]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"10281","type":"Disease","text":["seizure"],"offsets":[[291,298]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"10282","type":"Disease","text":["seizures"],"offsets":[[336,344]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"10283","type":"Chemical","text":["pilocarpine"],"offsets":[[403,414]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"10284","type":"Chemical","text":["pilocarpine"],"offsets":[[512,523]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"10285","type":"Disease","text":["seizures"],"offsets":[[532,540]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"10286","type":"Chemical","text":["digoxigenin"],"offsets":[[588,599]],"normalized":[{"db_name":"MESH","db_id":"D004076"}]},{"id":"10287","type":"Chemical","text":["pilocarpine"],"offsets":[[746,757]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"10288","type":"Chemical","text":["cresyl violet"],"offsets":[[865,878]],"normalized":[{"db_name":"MESH","db_id":"C028911"}]},{"id":"10289","type":"Disease","text":["neuronal degeneration"],"offsets":[[889,910]],"normalized":[{"db_name":"MESH","db_id":"D009410"}]},{"id":"10290","type":"Disease","text":["neuronal loss"],"offsets":[[1075,1088]],"normalized":[{"db_name":"MESH","db_id":"D009410"}]},{"id":"10291","type":"Disease","text":["seizure"],"offsets":[[1877,1884]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"10292","type":"Chemical","text":["GABA"],"offsets":[[1990,1994]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]}],"events":[],"coreferences":[],"relations":[{"id":"10293","type":"CID","arg1_id":"10278","arg2_id":"10279","normalized":[]},{"id":"10294","type":"CID","arg1_id":"10278","arg2_id":"10281","normalized":[]},{"id":"10295","type":"CID","arg1_id":"10278","arg2_id":"10282","normalized":[]},{"id":"10296","type":"CID","arg1_id":"10278","arg2_id":"10285","normalized":[]},{"id":"10297","type":"CID","arg1_id":"10278","arg2_id":"10291","normalized":[]},{"id":"10298","type":"CID","arg1_id":"10283","arg2_id":"10279","normalized":[]},{"id":"10299","type":"CID","arg1_id":"10283","arg2_id":"10281","normalized":[]},{"id":"10300","type":"CID","arg1_id":"10283","arg2_id":"10282","normalized":[]},{"id":"10301","type":"CID","arg1_id":"10283","arg2_id":"10285","normalized":[]},{"id":"10302","type":"CID","arg1_id":"10283","arg2_id":"10291","normalized":[]},{"id":"10303","type":"CID","arg1_id":"10284","arg2_id":"10279","normalized":[]},{"id":"10304","type":"CID","arg1_id":"10284","arg2_id":"10281","normalized":[]},{"id":"10305","type":"CID","arg1_id":"10284","arg2_id":"10282","normalized":[]},{"id":"10306","type":"CID","arg1_id":"10284","arg2_id":"10285","normalized":[]},{"id":"10307","type":"CID","arg1_id":"10284","arg2_id":"10291","normalized":[]},{"id":"10308","type":"CID","arg1_id":"10287","arg2_id":"10279","normalized":[]},{"id":"10309","type":"CID","arg1_id":"10287","arg2_id":"10281","normalized":[]},{"id":"10310","type":"CID","arg1_id":"10287","arg2_id":"10282","normalized":[]},{"id":"10311","type":"CID","arg1_id":"10287","arg2_id":"10285","normalized":[]},{"id":"10312","type":"CID","arg1_id":"10287","arg2_id":"10291","normalized":[]},{"id":"10313","type":"CID","arg1_id":"10278","arg2_id":"10289","normalized":[]},{"id":"10314","type":"CID","arg1_id":"10278","arg2_id":"10290","normalized":[]},{"id":"10315","type":"CID","arg1_id":"10283","arg2_id":"10289","normalized":[]},{"id":"10316","type":"CID","arg1_id":"10283","arg2_id":"10290","normalized":[]},{"id":"10317","type":"CID","arg1_id":"10284","arg2_id":"10289","normalized":[]},{"id":"10318","type":"CID","arg1_id":"10284","arg2_id":"10290","normalized":[]},{"id":"10319","type":"CID","arg1_id":"10287","arg2_id":"10289","normalized":[]},{"id":"10320","type":"CID","arg1_id":"10287","arg2_id":"10290","normalized":[]}]}
{"id":"10321","document_id":"7791169","passages":[{"id":"10322","type":"title","text":["Protective effect of misoprostol on indomethacin induced renal dysfunction in elderly patients."],"offsets":[[0,95]]},{"id":"10323","type":"abstract","text":["OBJECTIVE: To evaluate the possible protective effects of misoprostol on renal function in hospitalized elderly patients treated with indomethacin. METHODS: Forty-five hospitalized elderly patients (> 65 years old) who required therapy with nonsteroidal antiinflammatory drugs (NSAID) were randomly assigned to receive either indomethacin, 150 mg\/day (Group A), or indomethacin 150 mg\/day plus misoprostol at 0.6 mg\/day (Group B). Laboratory variables of renal function [serum creatinine, blood urea nitrogen (BUN) and electrolytes] were evaluated before initiation of therapy and every 2 days, until termination of the study (a period of at least 6 days). Response to treatment was estimated by the visual analog scale for severity of pain. RESULTS: Forty-two patients completed the study, 22 in Group A and 20 in Group B. BUN and creatinine increased by > 50% of baseline levels in 54 and 45% of Group A patients, respectively, compared to only 20 and 10% of Group B patients (p < 0.05). Potassium (K) increment of 0.6 mEq\/l or more was observed in 50% of Group A, but in only 15% of Group B patients (p < 0.05). The mean increments in BUN, creatinine, and K were reduced by 63, 80, and 42%, respectively, in Group B patients compared to Group A. Response to treatment did not differ significantly between the 2 groups. CONCLUSION: Hospitalized elderly patients are at risk for developing indomethacin related renal dysfunction. Addition of misoprostol can minimize this renal impairment without affecting pain control."],"offsets":[[96,1617]]}],"entities":[{"id":"10324","type":"Chemical","text":["misoprostol"],"offsets":[[21,32]],"normalized":[{"db_name":"MESH","db_id":"D016595"}]},{"id":"10325","type":"Chemical","text":["indomethacin"],"offsets":[[36,48]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"10326","type":"Disease","text":["renal dysfunction"],"offsets":[[57,74]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"10327","type":"Chemical","text":["misoprostol"],"offsets":[[154,165]],"normalized":[{"db_name":"MESH","db_id":"D016595"}]},{"id":"10328","type":"Chemical","text":["indomethacin"],"offsets":[[230,242]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"10329","type":"Chemical","text":["indomethacin"],"offsets":[[422,434]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"10330","type":"Chemical","text":["indomethacin"],"offsets":[[461,473]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"10331","type":"Chemical","text":["misoprostol"],"offsets":[[490,501]],"normalized":[{"db_name":"MESH","db_id":"D016595"}]},{"id":"10332","type":"Chemical","text":["creatinine"],"offsets":[[573,583]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"10333","type":"Chemical","text":["blood urea nitrogen"],"offsets":[[585,604]],"normalized":[{"db_name":"MESH","db_id":"D001806"}]},{"id":"10334","type":"Chemical","text":["BUN"],"offsets":[[606,609]],"normalized":[{"db_name":"MESH","db_id":"D001806"}]},{"id":"10335","type":"Disease","text":["pain"],"offsets":[[832,836]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"10336","type":"Chemical","text":["BUN"],"offsets":[[920,923]],"normalized":[{"db_name":"MESH","db_id":"D001806"}]},{"id":"10337","type":"Chemical","text":["creatinine"],"offsets":[[928,938]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"10338","type":"Chemical","text":["Potassium"],"offsets":[[1086,1095]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"10339","type":"Chemical","text":["K"],"offsets":[[1097,1098]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"10340","type":"Chemical","text":["BUN"],"offsets":[[1234,1237]],"normalized":[{"db_name":"MESH","db_id":"D001806"}]},{"id":"10341","type":"Chemical","text":["creatinine"],"offsets":[[1239,1249]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"10342","type":"Chemical","text":["K"],"offsets":[[1255,1256]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"10343","type":"Chemical","text":["indomethacin"],"offsets":[[1487,1499]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"10344","type":"Disease","text":["renal dysfunction"],"offsets":[[1508,1525]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"10345","type":"Chemical","text":["misoprostol"],"offsets":[[1539,1550]],"normalized":[{"db_name":"MESH","db_id":"D016595"}]},{"id":"10346","type":"Disease","text":["renal impairment"],"offsets":[[1569,1585]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"10347","type":"Disease","text":["pain"],"offsets":[[1604,1608]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]}],"events":[],"coreferences":[],"relations":[{"id":"10348","type":"CID","arg1_id":"10325","arg2_id":"10326","normalized":[]},{"id":"10349","type":"CID","arg1_id":"10325","arg2_id":"10344","normalized":[]},{"id":"10350","type":"CID","arg1_id":"10325","arg2_id":"10346","normalized":[]},{"id":"10351","type":"CID","arg1_id":"10328","arg2_id":"10326","normalized":[]},{"id":"10352","type":"CID","arg1_id":"10328","arg2_id":"10344","normalized":[]},{"id":"10353","type":"CID","arg1_id":"10328","arg2_id":"10346","normalized":[]},{"id":"10354","type":"CID","arg1_id":"10329","arg2_id":"10326","normalized":[]},{"id":"10355","type":"CID","arg1_id":"10329","arg2_id":"10344","normalized":[]},{"id":"10356","type":"CID","arg1_id":"10329","arg2_id":"10346","normalized":[]},{"id":"10357","type":"CID","arg1_id":"10330","arg2_id":"10326","normalized":[]},{"id":"10358","type":"CID","arg1_id":"10330","arg2_id":"10344","normalized":[]},{"id":"10359","type":"CID","arg1_id":"10330","arg2_id":"10346","normalized":[]},{"id":"10360","type":"CID","arg1_id":"10343","arg2_id":"10326","normalized":[]},{"id":"10361","type":"CID","arg1_id":"10343","arg2_id":"10344","normalized":[]},{"id":"10362","type":"CID","arg1_id":"10343","arg2_id":"10346","normalized":[]}]}
{"id":"10363","document_id":"6728084","passages":[{"id":"10364","type":"title","text":["Nephrotoxic effects of aminoglycoside treatment on renal protein reabsorption and accumulation."],"offsets":[[0,95]]},{"id":"10365","type":"abstract","text":["To quantify the effects of gentamicin, kanamycin and netilmicin on renal protein reabsorption and accumulation, these drugs were administered to rats intraperitoneally (30 mg\/kg\/day) for 7, 14 or 21 days. Scanning electron microscopy of the glomerular endothelia, urinary measurements of sodium, potassium, endogenous lysozyme, N-acetyl-beta-D-glucosaminidase (NAG) as well as clearance and accumulation experiments after i.v. administration of egg-white lysozyme and measurements of inulin clearance (GFR) were done in each treatment group. Gentamicin administration decreased diameter, density and shape of endothelial fenestrae. Kanamycin and netilmicin appeared to have no effect at the dose used. All three aminoglycosides decreased GFR and increased urinary excretion of sodium and potassium. While gentamicin and kanamycin decreased the percentage reabsorption and accumulation of lysozyme after i.v. administration of egg-white lysozyme netilmicin had no effect. Daily excretion of total protein, endogenous lysozyme and NAG increased only after treatment with kanamycin and gentamicin. Thus, aminoglycosides may act as nephrotoxicants at glomerular and\/or tubular level inducing impairment of renal reabsorption and accumulation of proteins."],"offsets":[[96,1346]]}],"entities":[{"id":"10366","type":"Disease","text":["Nephrotoxic"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"10367","type":"Chemical","text":["aminoglycoside"],"offsets":[[23,37]],"normalized":[{"db_name":"MESH","db_id":"D000617"}]},{"id":"10368","type":"Chemical","text":["gentamicin"],"offsets":[[123,133]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"10369","type":"Chemical","text":["kanamycin"],"offsets":[[135,144]],"normalized":[{"db_name":"MESH","db_id":"D007612"}]},{"id":"10370","type":"Chemical","text":["netilmicin"],"offsets":[[149,159]],"normalized":[{"db_name":"MESH","db_id":"D009428"}]},{"id":"10371","type":"Chemical","text":["sodium"],"offsets":[[384,390]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"10372","type":"Chemical","text":["potassium"],"offsets":[[392,401]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"10373","type":"Chemical","text":["Gentamicin"],"offsets":[[638,648]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"10374","type":"Chemical","text":["Kanamycin"],"offsets":[[728,737]],"normalized":[{"db_name":"MESH","db_id":"D007612"}]},{"id":"10375","type":"Chemical","text":["netilmicin"],"offsets":[[742,752]],"normalized":[{"db_name":"MESH","db_id":"D009428"}]},{"id":"10376","type":"Chemical","text":["aminoglycosides"],"offsets":[[808,823]],"normalized":[{"db_name":"MESH","db_id":"D000617"}]},{"id":"10377","type":"Chemical","text":["sodium"],"offsets":[[873,879]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"10378","type":"Chemical","text":["potassium"],"offsets":[[884,893]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"10379","type":"Chemical","text":["gentamicin"],"offsets":[[901,911]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"10380","type":"Chemical","text":["kanamycin"],"offsets":[[916,925]],"normalized":[{"db_name":"MESH","db_id":"D007612"}]},{"id":"10381","type":"Chemical","text":["netilmicin"],"offsets":[[1041,1051]],"normalized":[{"db_name":"MESH","db_id":"D009428"}]},{"id":"10382","type":"Chemical","text":["kanamycin"],"offsets":[[1165,1174]],"normalized":[{"db_name":"MESH","db_id":"D007612"}]},{"id":"10383","type":"Chemical","text":["gentamicin"],"offsets":[[1179,1189]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"10384","type":"Chemical","text":["aminoglycosides"],"offsets":[[1197,1212]],"normalized":[{"db_name":"MESH","db_id":"D000617"}]},{"id":"10385","type":"Disease","text":["impairment of renal reabsorption"],"offsets":[[1284,1316]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"10386","type":"CID","arg1_id":"10369","arg2_id":"10366","normalized":[]},{"id":"10387","type":"CID","arg1_id":"10369","arg2_id":"10385","normalized":[]},{"id":"10388","type":"CID","arg1_id":"10374","arg2_id":"10366","normalized":[]},{"id":"10389","type":"CID","arg1_id":"10374","arg2_id":"10385","normalized":[]},{"id":"10390","type":"CID","arg1_id":"10380","arg2_id":"10366","normalized":[]},{"id":"10391","type":"CID","arg1_id":"10380","arg2_id":"10385","normalized":[]},{"id":"10392","type":"CID","arg1_id":"10382","arg2_id":"10366","normalized":[]},{"id":"10393","type":"CID","arg1_id":"10382","arg2_id":"10385","normalized":[]},{"id":"10394","type":"CID","arg1_id":"10368","arg2_id":"10366","normalized":[]},{"id":"10395","type":"CID","arg1_id":"10368","arg2_id":"10385","normalized":[]},{"id":"10396","type":"CID","arg1_id":"10373","arg2_id":"10366","normalized":[]},{"id":"10397","type":"CID","arg1_id":"10373","arg2_id":"10385","normalized":[]},{"id":"10398","type":"CID","arg1_id":"10379","arg2_id":"10366","normalized":[]},{"id":"10399","type":"CID","arg1_id":"10379","arg2_id":"10385","normalized":[]},{"id":"10400","type":"CID","arg1_id":"10383","arg2_id":"10366","normalized":[]},{"id":"10401","type":"CID","arg1_id":"10383","arg2_id":"10385","normalized":[]}]}
{"id":"10402","document_id":"6111982","passages":[{"id":"10403","type":"title","text":["Pharmacology of GYKI-41 099 (chlorpropanol, Tobanum) a new potent beta-adrenergic antagonist."],"offsets":[[0,93]]},{"id":"10404","type":"abstract","text":["The compound GYKI-41 099, as a beta-adrenergic antagonist, is 3-8 times more potent than propranolol in vitro and in vivo. Its antiarrhythmic effectiveness surpasses that of propranolol and pindolol inhibiting the ouabain arrhythmia in dogs and cats. GYKI-41 900 has a negligible cardiodepressant activity; it is not cardioselective. The compound shows a rapid and long lasting effect. There was a prolonged elimination of the radioactivity after the injection of 14C-41 099 to rats and dogs. The half life of the unlabeled substance in humans was more than 10 hours."],"offsets":[[94,661]]}],"entities":[{"id":"10405","type":"Chemical","text":["GYKI-41 099"],"offsets":[[16,27]],"normalized":[{"db_name":"MESH","db_id":"C025725"}]},{"id":"10406","type":"Chemical","text":["chlorpropanol"],"offsets":[[29,42]],"normalized":[{"db_name":"MESH","db_id":"C025725"}]},{"id":"10407","type":"Chemical","text":["Tobanum"],"offsets":[[44,51]],"normalized":[{"db_name":"MESH","db_id":"C025725"}]},{"id":"10408","type":"Chemical","text":["GYKI-41 099"],"offsets":[[107,118]],"normalized":[{"db_name":"MESH","db_id":"C025725"}]},{"id":"10409","type":"Chemical","text":["propranolol"],"offsets":[[183,194]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"10410","type":"Chemical","text":["propranolol"],"offsets":[[268,279]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"10411","type":"Chemical","text":["pindolol"],"offsets":[[284,292]],"normalized":[{"db_name":"MESH","db_id":"D010869"}]},{"id":"10412","type":"Chemical","text":["ouabain"],"offsets":[[308,315]],"normalized":[{"db_name":"MESH","db_id":"D010042"}]},{"id":"10413","type":"Disease","text":["arrhythmia"],"offsets":[[316,326]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"10414","type":"Chemical","text":["GYKI-41 900"],"offsets":[[345,356]],"normalized":[]},{"id":"10415","type":"Chemical","text":["14C-41 099"],"offsets":[[558,568]],"normalized":[]}],"events":[],"coreferences":[],"relations":[{"id":"10416","type":"CID","arg1_id":"10412","arg2_id":"10413","normalized":[]}]}
{"id":"10417","document_id":"3123611","passages":[{"id":"10418","type":"title","text":["Chorea associated with oral contraception."],"offsets":[[0,42]]},{"id":"10419","type":"abstract","text":["Three patients developed chorea while receiving oral contraceptives. Two were young patients whose chorea developed long after treatment had been started and disappeared soon after it had been discontinued. The third patient had acute amphetamine-induced chorea after prolonged oral contraception. Prolonged administration of female sex hormones is a possible cause of chorea in women who have not previously had chorea or rheumatic fever."],"offsets":[[43,482]]}],"entities":[{"id":"10420","type":"Disease","text":["Chorea"],"offsets":[[0,6]],"normalized":[{"db_name":"MESH","db_id":"D002819"}]},{"id":"10421","type":"Chemical","text":["oral contraception"],"offsets":[[23,41]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"10422","type":"Disease","text":["chorea"],"offsets":[[68,74]],"normalized":[{"db_name":"MESH","db_id":"D002819"}]},{"id":"10423","type":"Chemical","text":["oral contraceptives"],"offsets":[[91,110]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"10424","type":"Disease","text":["chorea"],"offsets":[[142,148]],"normalized":[{"db_name":"MESH","db_id":"D002819"}]},{"id":"10425","type":"Chemical","text":["amphetamine"],"offsets":[[278,289]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"10426","type":"Disease","text":["chorea"],"offsets":[[298,304]],"normalized":[{"db_name":"MESH","db_id":"D002819"}]},{"id":"10427","type":"Chemical","text":["oral contraception"],"offsets":[[321,339]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"10428","type":"Disease","text":["chorea"],"offsets":[[412,418]],"normalized":[{"db_name":"MESH","db_id":"D002819"}]},{"id":"10429","type":"Disease","text":["chorea"],"offsets":[[456,462]],"normalized":[{"db_name":"MESH","db_id":"D002819"}]},{"id":"10430","type":"Disease","text":["rheumatic fever"],"offsets":[[466,481]],"normalized":[{"db_name":"MESH","db_id":"D012213"}]}],"events":[],"coreferences":[],"relations":[{"id":"10431","type":"CID","arg1_id":"10421","arg2_id":"10420","normalized":[]},{"id":"10432","type":"CID","arg1_id":"10421","arg2_id":"10422","normalized":[]},{"id":"10433","type":"CID","arg1_id":"10421","arg2_id":"10424","normalized":[]},{"id":"10434","type":"CID","arg1_id":"10421","arg2_id":"10426","normalized":[]},{"id":"10435","type":"CID","arg1_id":"10421","arg2_id":"10428","normalized":[]},{"id":"10436","type":"CID","arg1_id":"10421","arg2_id":"10429","normalized":[]},{"id":"10437","type":"CID","arg1_id":"10423","arg2_id":"10420","normalized":[]},{"id":"10438","type":"CID","arg1_id":"10423","arg2_id":"10422","normalized":[]},{"id":"10439","type":"CID","arg1_id":"10423","arg2_id":"10424","normalized":[]},{"id":"10440","type":"CID","arg1_id":"10423","arg2_id":"10426","normalized":[]},{"id":"10441","type":"CID","arg1_id":"10423","arg2_id":"10428","normalized":[]},{"id":"10442","type":"CID","arg1_id":"10423","arg2_id":"10429","normalized":[]},{"id":"10443","type":"CID","arg1_id":"10427","arg2_id":"10420","normalized":[]},{"id":"10444","type":"CID","arg1_id":"10427","arg2_id":"10422","normalized":[]},{"id":"10445","type":"CID","arg1_id":"10427","arg2_id":"10424","normalized":[]},{"id":"10446","type":"CID","arg1_id":"10427","arg2_id":"10426","normalized":[]},{"id":"10447","type":"CID","arg1_id":"10427","arg2_id":"10428","normalized":[]},{"id":"10448","type":"CID","arg1_id":"10427","arg2_id":"10429","normalized":[]},{"id":"10449","type":"CID","arg1_id":"10425","arg2_id":"10420","normalized":[]},{"id":"10450","type":"CID","arg1_id":"10425","arg2_id":"10422","normalized":[]},{"id":"10451","type":"CID","arg1_id":"10425","arg2_id":"10424","normalized":[]},{"id":"10452","type":"CID","arg1_id":"10425","arg2_id":"10426","normalized":[]},{"id":"10453","type":"CID","arg1_id":"10425","arg2_id":"10428","normalized":[]},{"id":"10454","type":"CID","arg1_id":"10425","arg2_id":"10429","normalized":[]}]}
{"id":"10455","document_id":"761833","passages":[{"id":"10456","type":"title","text":["Reversal of ammonia coma in rats by L-dopa: a peripheral effect."],"offsets":[[0,64]]},{"id":"10457","type":"abstract","text":["Ammonia coma was produced in rats within 10 to 15 minutes of an intraperitonealinjection of 1.7 mmol NH4CL. This coma was prevented with 1.68 mmol L-dopa given by gastric intubation 15 minutes before the ammonium salt injection. The effect of L-dopa was correlated with a decrease in blood and brain ammonia, an increase in brain dopamine, and an increase in renal excretion of ammonia and urea. Intraventricular infusion of dopamine sufficient to raise the brain dopamine to the same extent did not prevent the ammonia coma nor affect the blood and brain ammonia concentrations. Bilateral nephrectomy eliminated the beneficial effect of L-dopa on blood and brain ammonia and the ammonia coma was not prevented. Thus, the reduction in blood and brain ammonia and the prevention of ammonia coma after L-dopa, can be accounted for by the peripheral effect of dopamine on renal function rather than its central action. These results provide a reasonable explanation for the beneficial effects observed in some encephalopathic patients receiving L-dopa."],"offsets":[[65,1114]]}],"entities":[{"id":"10458","type":"Chemical","text":["ammonia"],"offsets":[[12,19]],"normalized":[{"db_name":"MESH","db_id":"D000641"}]},{"id":"10459","type":"Disease","text":["coma"],"offsets":[[20,24]],"normalized":[{"db_name":"MESH","db_id":"D003128"}]},{"id":"10460","type":"Chemical","text":["L-dopa"],"offsets":[[36,42]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"10461","type":"Chemical","text":["Ammonia"],"offsets":[[65,72]],"normalized":[{"db_name":"MESH","db_id":"D000641"}]},{"id":"10462","type":"Disease","text":["coma"],"offsets":[[73,77]],"normalized":[{"db_name":"MESH","db_id":"D003128"}]},{"id":"10463","type":"Chemical","text":["NH4CL"],"offsets":[[166,171]],"normalized":[{"db_name":"MESH","db_id":"D000643"}]},{"id":"10464","type":"Disease","text":["coma"],"offsets":[[178,182]],"normalized":[{"db_name":"MESH","db_id":"D003128"}]},{"id":"10465","type":"Chemical","text":["L-dopa"],"offsets":[[212,218]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"10466","type":"Chemical","text":["ammonium salt"],"offsets":[[269,282]],"normalized":[{"db_name":"MESH","db_id":"D064751"}]},{"id":"10467","type":"Chemical","text":["L-dopa"],"offsets":[[308,314]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"10468","type":"Chemical","text":["ammonia"],"offsets":[[365,372]],"normalized":[{"db_name":"MESH","db_id":"D000641"}]},{"id":"10469","type":"Chemical","text":["dopamine"],"offsets":[[395,403]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"10470","type":"Chemical","text":["ammonia"],"offsets":[[443,450]],"normalized":[{"db_name":"MESH","db_id":"D000641"}]},{"id":"10471","type":"Chemical","text":["urea"],"offsets":[[455,459]],"normalized":[{"db_name":"MESH","db_id":"D014508"}]},{"id":"10472","type":"Chemical","text":["dopamine"],"offsets":[[490,498]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"10473","type":"Chemical","text":["dopamine"],"offsets":[[529,537]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"10474","type":"Chemical","text":["ammonia"],"offsets":[[577,584]],"normalized":[{"db_name":"MESH","db_id":"D000641"}]},{"id":"10475","type":"Disease","text":["coma"],"offsets":[[585,589]],"normalized":[{"db_name":"MESH","db_id":"D003128"}]},{"id":"10476","type":"Chemical","text":["ammonia"],"offsets":[[621,628]],"normalized":[{"db_name":"MESH","db_id":"D000641"}]},{"id":"10477","type":"Chemical","text":["L-dopa"],"offsets":[[703,709]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"10478","type":"Chemical","text":["ammonia"],"offsets":[[729,736]],"normalized":[{"db_name":"MESH","db_id":"D000641"}]},{"id":"10479","type":"Chemical","text":["ammonia"],"offsets":[[745,752]],"normalized":[{"db_name":"MESH","db_id":"D000641"}]},{"id":"10480","type":"Disease","text":["coma"],"offsets":[[753,757]],"normalized":[{"db_name":"MESH","db_id":"D003128"}]},{"id":"10481","type":"Chemical","text":["ammonia"],"offsets":[[816,823]],"normalized":[{"db_name":"MESH","db_id":"D000641"}]},{"id":"10482","type":"Chemical","text":["ammonia"],"offsets":[[846,853]],"normalized":[{"db_name":"MESH","db_id":"D000641"}]},{"id":"10483","type":"Disease","text":["coma"],"offsets":[[854,858]],"normalized":[{"db_name":"MESH","db_id":"D003128"}]},{"id":"10484","type":"Chemical","text":["L-dopa"],"offsets":[[865,871]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"10485","type":"Chemical","text":["dopamine"],"offsets":[[922,930]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"10486","type":"Disease","text":["encephalopathic"],"offsets":[[1072,1087]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"10487","type":"Chemical","text":["L-dopa"],"offsets":[[1107,1113]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]}],"events":[],"coreferences":[],"relations":[{"id":"10488","type":"CID","arg1_id":"10463","arg2_id":"10459","normalized":[]},{"id":"10489","type":"CID","arg1_id":"10463","arg2_id":"10462","normalized":[]},{"id":"10490","type":"CID","arg1_id":"10463","arg2_id":"10464","normalized":[]},{"id":"10491","type":"CID","arg1_id":"10463","arg2_id":"10475","normalized":[]},{"id":"10492","type":"CID","arg1_id":"10463","arg2_id":"10480","normalized":[]},{"id":"10493","type":"CID","arg1_id":"10463","arg2_id":"10483","normalized":[]}]}
{"id":"10494","document_id":"18589141","passages":[{"id":"10495","type":"title","text":["Heparin-induced thrombocytopenia after liver transplantation."],"offsets":[[0,61]]},{"id":"10496","type":"abstract","text":["BACKGROUND: Unfractionated heparin sodium (UFH) or low-molecular weight heparin (LMWH) is used in anticoagulant protocols at several institutions to prevent thrombosis after liver transplantation. Heparin-induced thrombocytopenia (HIT) is an adverse immune-mediated reaction to heparin, resulting in platelet count decreases of more than 50%. The frequencies of HIT after liver transplantation and platelet factor 4\/heparin-reactive antibody (HIT antibody) positivity in liver transplantation patients, however, are unknown. PATIENTS AND METHODS: The 32 men and 20 women underwent living donor liver transplantation. We started LMWH (25 IU\/kg\/h) on postoperative day (POD) 1, switching to UFH (5000 U\/d) on POD 2 or 3. The dose of UFH was changed according to the activated clotting time level. HIT antibody levels were measured the day before surgery and on POD 7 and 14. Platelet count was measured daily for 3 weeks. RESULTS: The average platelet counts preoperatively, and on POD 7, 14, and 21 were 65, 88, 149, and 169 x 10(9)\/L, respectively. Two patients developed hepatic artery thrombosis on POD 11 and 19, respectively, although they were HIT antibody-negative and their platelet counts were stable. In 2 other patients, the platelet count decreased suddenly from 107 x 10(9)\/L on POD 4 to 65 x 10(9)\/L on POD 6 and from 76 x 10(9)\/L on POD 7 to 33 x 10(9)\/L on POD 9, respectively. The heparin-induced platelet aggregation test was negative in these patients. The percentage of HIT antibody-positive patients was 0.5% preoperatively, 5.6% on POD 7, and 5.6% on POD 14. None of the subjects\/patients developed UFH-related HIT. CONCLUSIONS: In our series, the occurrence of HIT after liver transplantation was uncommon."],"offsets":[[62,1790]]}],"entities":[{"id":"10497","type":"Chemical","text":["Heparin"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"10498","type":"Disease","text":["thrombocytopenia"],"offsets":[[16,32]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"10499","type":"Chemical","text":["Unfractionated heparin sodium"],"offsets":[[74,103]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"10500","type":"Chemical","text":["UFH"],"offsets":[[105,108]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"10501","type":"Chemical","text":["low-molecular weight heparin"],"offsets":[[113,141]],"normalized":[{"db_name":"MESH","db_id":"D006495"}]},{"id":"10502","type":"Disease","text":["thrombosis"],"offsets":[[219,229]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]},{"id":"10503","type":"Chemical","text":["Heparin"],"offsets":[[259,266]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"10504","type":"Disease","text":["thrombocytopenia"],"offsets":[[275,291]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"10505","type":"Disease","text":["HIT"],"offsets":[[293,296]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"10506","type":"Chemical","text":["heparin"],"offsets":[[340,347]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"10507","type":"Disease","text":["HIT"],"offsets":[[424,427]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"10508","type":"Chemical","text":["heparin"],"offsets":[[478,485]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"10509","type":"Disease","text":["HIT"],"offsets":[[505,508]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"10510","type":"Chemical","text":["UFH"],"offsets":[[751,754]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"10511","type":"Chemical","text":["UFH"],"offsets":[[793,796]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"10512","type":"Disease","text":["HIT"],"offsets":[[857,860]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"10513","type":"Disease","text":["thrombosis"],"offsets":[[1149,1159]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]},{"id":"10514","type":"Disease","text":["HIT"],"offsets":[[1211,1214]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"10515","type":"Chemical","text":["heparin"],"offsets":[[1459,1466]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"10516","type":"Disease","text":["platelet aggregation"],"offsets":[[1475,1495]],"normalized":[{"db_name":"MESH","db_id":"D001791"}]},{"id":"10517","type":"Disease","text":["HIT"],"offsets":[[1551,1554]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"10518","type":"Chemical","text":["UFH"],"offsets":[[1682,1685]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"10519","type":"Disease","text":["HIT"],"offsets":[[1694,1697]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"10520","type":"Disease","text":["HIT"],"offsets":[[1745,1748]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]}],"events":[],"coreferences":[],"relations":[{"id":"10521","type":"CID","arg1_id":"10497","arg2_id":"10498","normalized":[]},{"id":"10522","type":"CID","arg1_id":"10497","arg2_id":"10504","normalized":[]},{"id":"10523","type":"CID","arg1_id":"10497","arg2_id":"10505","normalized":[]},{"id":"10524","type":"CID","arg1_id":"10497","arg2_id":"10507","normalized":[]},{"id":"10525","type":"CID","arg1_id":"10497","arg2_id":"10509","normalized":[]},{"id":"10526","type":"CID","arg1_id":"10497","arg2_id":"10512","normalized":[]},{"id":"10527","type":"CID","arg1_id":"10497","arg2_id":"10514","normalized":[]},{"id":"10528","type":"CID","arg1_id":"10497","arg2_id":"10517","normalized":[]},{"id":"10529","type":"CID","arg1_id":"10497","arg2_id":"10519","normalized":[]},{"id":"10530","type":"CID","arg1_id":"10497","arg2_id":"10520","normalized":[]},{"id":"10531","type":"CID","arg1_id":"10499","arg2_id":"10498","normalized":[]},{"id":"10532","type":"CID","arg1_id":"10499","arg2_id":"10504","normalized":[]},{"id":"10533","type":"CID","arg1_id":"10499","arg2_id":"10505","normalized":[]},{"id":"10534","type":"CID","arg1_id":"10499","arg2_id":"10507","normalized":[]},{"id":"10535","type":"CID","arg1_id":"10499","arg2_id":"10509","normalized":[]},{"id":"10536","type":"CID","arg1_id":"10499","arg2_id":"10512","normalized":[]},{"id":"10537","type":"CID","arg1_id":"10499","arg2_id":"10514","normalized":[]},{"id":"10538","type":"CID","arg1_id":"10499","arg2_id":"10517","normalized":[]},{"id":"10539","type":"CID","arg1_id":"10499","arg2_id":"10519","normalized":[]},{"id":"10540","type":"CID","arg1_id":"10499","arg2_id":"10520","normalized":[]},{"id":"10541","type":"CID","arg1_id":"10500","arg2_id":"10498","normalized":[]},{"id":"10542","type":"CID","arg1_id":"10500","arg2_id":"10504","normalized":[]},{"id":"10543","type":"CID","arg1_id":"10500","arg2_id":"10505","normalized":[]},{"id":"10544","type":"CID","arg1_id":"10500","arg2_id":"10507","normalized":[]},{"id":"10545","type":"CID","arg1_id":"10500","arg2_id":"10509","normalized":[]},{"id":"10546","type":"CID","arg1_id":"10500","arg2_id":"10512","normalized":[]},{"id":"10547","type":"CID","arg1_id":"10500","arg2_id":"10514","normalized":[]},{"id":"10548","type":"CID","arg1_id":"10500","arg2_id":"10517","normalized":[]},{"id":"10549","type":"CID","arg1_id":"10500","arg2_id":"10519","normalized":[]},{"id":"10550","type":"CID","arg1_id":"10500","arg2_id":"10520","normalized":[]},{"id":"10551","type":"CID","arg1_id":"10503","arg2_id":"10498","normalized":[]},{"id":"10552","type":"CID","arg1_id":"10503","arg2_id":"10504","normalized":[]},{"id":"10553","type":"CID","arg1_id":"10503","arg2_id":"10505","normalized":[]},{"id":"10554","type":"CID","arg1_id":"10503","arg2_id":"10507","normalized":[]},{"id":"10555","type":"CID","arg1_id":"10503","arg2_id":"10509","normalized":[]},{"id":"10556","type":"CID","arg1_id":"10503","arg2_id":"10512","normalized":[]},{"id":"10557","type":"CID","arg1_id":"10503","arg2_id":"10514","normalized":[]},{"id":"10558","type":"CID","arg1_id":"10503","arg2_id":"10517","normalized":[]},{"id":"10559","type":"CID","arg1_id":"10503","arg2_id":"10519","normalized":[]},{"id":"10560","type":"CID","arg1_id":"10503","arg2_id":"10520","normalized":[]},{"id":"10561","type":"CID","arg1_id":"10506","arg2_id":"10498","normalized":[]},{"id":"10562","type":"CID","arg1_id":"10506","arg2_id":"10504","normalized":[]},{"id":"10563","type":"CID","arg1_id":"10506","arg2_id":"10505","normalized":[]},{"id":"10564","type":"CID","arg1_id":"10506","arg2_id":"10507","normalized":[]},{"id":"10565","type":"CID","arg1_id":"10506","arg2_id":"10509","normalized":[]},{"id":"10566","type":"CID","arg1_id":"10506","arg2_id":"10512","normalized":[]},{"id":"10567","type":"CID","arg1_id":"10506","arg2_id":"10514","normalized":[]},{"id":"10568","type":"CID","arg1_id":"10506","arg2_id":"10517","normalized":[]},{"id":"10569","type":"CID","arg1_id":"10506","arg2_id":"10519","normalized":[]},{"id":"10570","type":"CID","arg1_id":"10506","arg2_id":"10520","normalized":[]},{"id":"10571","type":"CID","arg1_id":"10508","arg2_id":"10498","normalized":[]},{"id":"10572","type":"CID","arg1_id":"10508","arg2_id":"10504","normalized":[]},{"id":"10573","type":"CID","arg1_id":"10508","arg2_id":"10505","normalized":[]},{"id":"10574","type":"CID","arg1_id":"10508","arg2_id":"10507","normalized":[]},{"id":"10575","type":"CID","arg1_id":"10508","arg2_id":"10509","normalized":[]},{"id":"10576","type":"CID","arg1_id":"10508","arg2_id":"10512","normalized":[]},{"id":"10577","type":"CID","arg1_id":"10508","arg2_id":"10514","normalized":[]},{"id":"10578","type":"CID","arg1_id":"10508","arg2_id":"10517","normalized":[]},{"id":"10579","type":"CID","arg1_id":"10508","arg2_id":"10519","normalized":[]},{"id":"10580","type":"CID","arg1_id":"10508","arg2_id":"10520","normalized":[]},{"id":"10581","type":"CID","arg1_id":"10510","arg2_id":"10498","normalized":[]},{"id":"10582","type":"CID","arg1_id":"10510","arg2_id":"10504","normalized":[]},{"id":"10583","type":"CID","arg1_id":"10510","arg2_id":"10505","normalized":[]},{"id":"10584","type":"CID","arg1_id":"10510","arg2_id":"10507","normalized":[]},{"id":"10585","type":"CID","arg1_id":"10510","arg2_id":"10509","normalized":[]},{"id":"10586","type":"CID","arg1_id":"10510","arg2_id":"10512","normalized":[]},{"id":"10587","type":"CID","arg1_id":"10510","arg2_id":"10514","normalized":[]},{"id":"10588","type":"CID","arg1_id":"10510","arg2_id":"10517","normalized":[]},{"id":"10589","type":"CID","arg1_id":"10510","arg2_id":"10519","normalized":[]},{"id":"10590","type":"CID","arg1_id":"10510","arg2_id":"10520","normalized":[]},{"id":"10591","type":"CID","arg1_id":"10511","arg2_id":"10498","normalized":[]},{"id":"10592","type":"CID","arg1_id":"10511","arg2_id":"10504","normalized":[]},{"id":"10593","type":"CID","arg1_id":"10511","arg2_id":"10505","normalized":[]},{"id":"10594","type":"CID","arg1_id":"10511","arg2_id":"10507","normalized":[]},{"id":"10595","type":"CID","arg1_id":"10511","arg2_id":"10509","normalized":[]},{"id":"10596","type":"CID","arg1_id":"10511","arg2_id":"10512","normalized":[]},{"id":"10597","type":"CID","arg1_id":"10511","arg2_id":"10514","normalized":[]},{"id":"10598","type":"CID","arg1_id":"10511","arg2_id":"10517","normalized":[]},{"id":"10599","type":"CID","arg1_id":"10511","arg2_id":"10519","normalized":[]},{"id":"10600","type":"CID","arg1_id":"10511","arg2_id":"10520","normalized":[]},{"id":"10601","type":"CID","arg1_id":"10515","arg2_id":"10498","normalized":[]},{"id":"10602","type":"CID","arg1_id":"10515","arg2_id":"10504","normalized":[]},{"id":"10603","type":"CID","arg1_id":"10515","arg2_id":"10505","normalized":[]},{"id":"10604","type":"CID","arg1_id":"10515","arg2_id":"10507","normalized":[]},{"id":"10605","type":"CID","arg1_id":"10515","arg2_id":"10509","normalized":[]},{"id":"10606","type":"CID","arg1_id":"10515","arg2_id":"10512","normalized":[]},{"id":"10607","type":"CID","arg1_id":"10515","arg2_id":"10514","normalized":[]},{"id":"10608","type":"CID","arg1_id":"10515","arg2_id":"10517","normalized":[]},{"id":"10609","type":"CID","arg1_id":"10515","arg2_id":"10519","normalized":[]},{"id":"10610","type":"CID","arg1_id":"10515","arg2_id":"10520","normalized":[]},{"id":"10611","type":"CID","arg1_id":"10518","arg2_id":"10498","normalized":[]},{"id":"10612","type":"CID","arg1_id":"10518","arg2_id":"10504","normalized":[]},{"id":"10613","type":"CID","arg1_id":"10518","arg2_id":"10505","normalized":[]},{"id":"10614","type":"CID","arg1_id":"10518","arg2_id":"10507","normalized":[]},{"id":"10615","type":"CID","arg1_id":"10518","arg2_id":"10509","normalized":[]},{"id":"10616","type":"CID","arg1_id":"10518","arg2_id":"10512","normalized":[]},{"id":"10617","type":"CID","arg1_id":"10518","arg2_id":"10514","normalized":[]},{"id":"10618","type":"CID","arg1_id":"10518","arg2_id":"10517","normalized":[]},{"id":"10619","type":"CID","arg1_id":"10518","arg2_id":"10519","normalized":[]},{"id":"10620","type":"CID","arg1_id":"10518","arg2_id":"10520","normalized":[]}]}
{"id":"10621","document_id":"16418614","passages":[{"id":"10622","type":"title","text":["PTU-associated vasculitis in a girl with Turner Syndrome and Graves' disease."],"offsets":[[0,77]]},{"id":"10623","type":"abstract","text":["Palpable purpura is a concerning clinical finding in pediatric patients and can have many causes, including infectious and autoimmune processes. A rare cause, drug-induced vasculitis, may result from the production of antineutrophil cytoplasmic antibodies (ANCAs) in response to a medication. We report a girl with Turner syndrome and Graves' disease who presented with palpable purpuric lesions. The diagnosis of propylthiouracil (PTU)-associated vasculitis was made by observation of consistent clinical features, the detection of elevated ANA and ANCA in the blood, and the observed clinical resolution of symptoms following withdrawal of PTU. Subsequent treatment of persistent hyperthyroidism with radioablation did not result in an exacerbation of the vasculitis, a complication described in prior case reports."],"offsets":[[78,895]]}],"entities":[{"id":"10624","type":"Chemical","text":["PTU"],"offsets":[[0,3]],"normalized":[{"db_name":"MESH","db_id":"D011441"}]},{"id":"10625","type":"Disease","text":["vasculitis"],"offsets":[[15,25]],"normalized":[{"db_name":"MESH","db_id":"D014657"}]},{"id":"10626","type":"Disease","text":["Turner Syndrome"],"offsets":[[41,56]],"normalized":[{"db_name":"MESH","db_id":"D014424"}]},{"id":"10627","type":"Disease","text":["Graves' disease"],"offsets":[[61,76]],"normalized":[{"db_name":"MESH","db_id":"D006111"}]},{"id":"10628","type":"Disease","text":["purpura"],"offsets":[[87,94]],"normalized":[{"db_name":"MESH","db_id":"D011693"}]},{"id":"10629","type":"Disease","text":["vasculitis"],"offsets":[[250,260]],"normalized":[{"db_name":"MESH","db_id":"D014657"}]},{"id":"10630","type":"Disease","text":["Turner syndrome"],"offsets":[[393,408]],"normalized":[{"db_name":"MESH","db_id":"D014424"}]},{"id":"10631","type":"Disease","text":["Graves' disease"],"offsets":[[413,428]],"normalized":[{"db_name":"MESH","db_id":"D006111"}]},{"id":"10632","type":"Disease","text":["purpuric lesions"],"offsets":[[457,473]],"normalized":[{"db_name":"MESH","db_id":"D011693"}]},{"id":"10633","type":"Chemical","text":["propylthiouracil"],"offsets":[[492,508]],"normalized":[{"db_name":"MESH","db_id":"D011441"}]},{"id":"10634","type":"Chemical","text":["PTU"],"offsets":[[510,513]],"normalized":[{"db_name":"MESH","db_id":"D011441"}]},{"id":"10635","type":"Disease","text":["vasculitis"],"offsets":[[526,536]],"normalized":[{"db_name":"MESH","db_id":"D014657"}]},{"id":"10636","type":"Chemical","text":["PTU"],"offsets":[[720,723]],"normalized":[{"db_name":"MESH","db_id":"D011441"}]},{"id":"10637","type":"Disease","text":["hyperthyroidism"],"offsets":[[760,775]],"normalized":[{"db_name":"MESH","db_id":"D006980"}]},{"id":"10638","type":"Disease","text":["vasculitis"],"offsets":[[836,846]],"normalized":[{"db_name":"MESH","db_id":"D014657"}]}],"events":[],"coreferences":[],"relations":[{"id":"10639","type":"CID","arg1_id":"10624","arg2_id":"10625","normalized":[]},{"id":"10640","type":"CID","arg1_id":"10624","arg2_id":"10629","normalized":[]},{"id":"10641","type":"CID","arg1_id":"10624","arg2_id":"10635","normalized":[]},{"id":"10642","type":"CID","arg1_id":"10624","arg2_id":"10638","normalized":[]},{"id":"10643","type":"CID","arg1_id":"10633","arg2_id":"10625","normalized":[]},{"id":"10644","type":"CID","arg1_id":"10633","arg2_id":"10629","normalized":[]},{"id":"10645","type":"CID","arg1_id":"10633","arg2_id":"10635","normalized":[]},{"id":"10646","type":"CID","arg1_id":"10633","arg2_id":"10638","normalized":[]},{"id":"10647","type":"CID","arg1_id":"10634","arg2_id":"10625","normalized":[]},{"id":"10648","type":"CID","arg1_id":"10634","arg2_id":"10629","normalized":[]},{"id":"10649","type":"CID","arg1_id":"10634","arg2_id":"10635","normalized":[]},{"id":"10650","type":"CID","arg1_id":"10634","arg2_id":"10638","normalized":[]},{"id":"10651","type":"CID","arg1_id":"10636","arg2_id":"10625","normalized":[]},{"id":"10652","type":"CID","arg1_id":"10636","arg2_id":"10629","normalized":[]},{"id":"10653","type":"CID","arg1_id":"10636","arg2_id":"10635","normalized":[]},{"id":"10654","type":"CID","arg1_id":"10636","arg2_id":"10638","normalized":[]}]}
{"id":"10655","document_id":"15893386","passages":[{"id":"10656","type":"title","text":["Succinylcholine-induced masseter muscle rigidity during bronchoscopic removal of a tracheal foreign body."],"offsets":[[0,105]]},{"id":"10657","type":"abstract","text":["Masseter muscle rigidity during general anesthesia is considered an early warning sign of a possible episode of malignant hyperthermia. The decision whether to continue or discontinue the procedure depends on the urgency of the surgery and severity of masseter muscle rigidity. Here, we describe a case of severe masseter muscle rigidity (jaw of steel) after succinylcholine (Sch) administration during general anesthetic management for rigid bronchoscopic removal of a tracheal foreign body. Anesthesia was continued uneventfully with propofol infusion while all facilities were available to detect and treat malignant hyperthermia."],"offsets":[[106,739]]}],"entities":[{"id":"10658","type":"Chemical","text":["Succinylcholine"],"offsets":[[0,15]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"10659","type":"Disease","text":["masseter muscle rigidity"],"offsets":[[24,48]],"normalized":[{"db_name":"MESH","db_id":"D014313"}]},{"id":"10660","type":"Disease","text":["Masseter muscle rigidity"],"offsets":[[106,130]],"normalized":[{"db_name":"MESH","db_id":"D014313"}]},{"id":"10661","type":"Disease","text":["malignant hyperthermia"],"offsets":[[218,240]],"normalized":[{"db_name":"MESH","db_id":"D008305"}]},{"id":"10662","type":"Disease","text":["masseter muscle rigidity"],"offsets":[[358,382]],"normalized":[{"db_name":"MESH","db_id":"D014313"}]},{"id":"10663","type":"Disease","text":["masseter muscle rigidity"],"offsets":[[419,443]],"normalized":[{"db_name":"MESH","db_id":"D014313"}]},{"id":"10664","type":"Disease","text":["jaw of steel"],"offsets":[[445,457]],"normalized":[{"db_name":"MESH","db_id":"D014313"}]},{"id":"10665","type":"Chemical","text":["succinylcholine"],"offsets":[[465,480]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"10666","type":"Chemical","text":["Sch"],"offsets":[[482,485]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"10667","type":"Chemical","text":["propofol"],"offsets":[[642,650]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"10668","type":"Disease","text":["malignant hyperthermia"],"offsets":[[716,738]],"normalized":[{"db_name":"MESH","db_id":"D008305"}]}],"events":[],"coreferences":[],"relations":[{"id":"10669","type":"CID","arg1_id":"10658","arg2_id":"10659","normalized":[]},{"id":"10670","type":"CID","arg1_id":"10658","arg2_id":"10660","normalized":[]},{"id":"10671","type":"CID","arg1_id":"10658","arg2_id":"10662","normalized":[]},{"id":"10672","type":"CID","arg1_id":"10658","arg2_id":"10663","normalized":[]},{"id":"10673","type":"CID","arg1_id":"10658","arg2_id":"10664","normalized":[]},{"id":"10674","type":"CID","arg1_id":"10665","arg2_id":"10659","normalized":[]},{"id":"10675","type":"CID","arg1_id":"10665","arg2_id":"10660","normalized":[]},{"id":"10676","type":"CID","arg1_id":"10665","arg2_id":"10662","normalized":[]},{"id":"10677","type":"CID","arg1_id":"10665","arg2_id":"10663","normalized":[]},{"id":"10678","type":"CID","arg1_id":"10665","arg2_id":"10664","normalized":[]},{"id":"10679","type":"CID","arg1_id":"10666","arg2_id":"10659","normalized":[]},{"id":"10680","type":"CID","arg1_id":"10666","arg2_id":"10660","normalized":[]},{"id":"10681","type":"CID","arg1_id":"10666","arg2_id":"10662","normalized":[]},{"id":"10682","type":"CID","arg1_id":"10666","arg2_id":"10663","normalized":[]},{"id":"10683","type":"CID","arg1_id":"10666","arg2_id":"10664","normalized":[]}]}
{"id":"10684","document_id":"15814210","passages":[{"id":"10685","type":"title","text":["Minor neurological dysfunction, cognitive development, and somatic development at the age of 3 to 7 years after dexamethasone treatment in very-low birth-weight infants."],"offsets":[[0,169]]},{"id":"10686","type":"abstract","text":["The objective of this study was to assess minor neurological dysfunction, cognitive development, and somatic development after dexamethasone therapy in very-low-birthweight infants. Thirty-three children after dexamethasone treatment were matched to 33 children without dexamethasone treatment. Data were assessed at the age of 3-7 years. Dexamethasone was started between the 7th and the 28th day of life over 7 days with a total dose of 2.35 mg\/kg\/day. Exclusion criteria were asphyxia, malformations, major surgical interventions, small for gestational age, intraventricular haemorrhage grades III and IV, periventricular leukomalacia, and severe psychomotor retardation. Each child was examined by a neuropediatrician for minor neurological dysfunctions and tested by a psychologist for cognitive development with a Kaufman Assessment Battery for Children and a Draw-a-Man Test. There were no differences in demographic data, growth, and socio-economic status between the two groups. Fine motor skills and gross motor function were significantly better in the control group (p<0.01). In the Draw-a-Man Test, the control group showed better results (p<0.001). There were no differences in development of speech, social development, and the Kaufman Assessment Battery for Children. After dexamethasone treatment, children showed a higher rate of minor neurological dysfunctions. Neurological development was affected even without neurological diagnosis. Further long-term follow-up studies will be necessary to fully evaluate the impact of dexamethasone on neurological and cognitive development."],"offsets":[[170,1768]]}],"entities":[{"id":"10687","type":"Disease","text":["neurological dysfunction"],"offsets":[[6,30]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"10688","type":"Chemical","text":["dexamethasone"],"offsets":[[112,125]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"10689","type":"Disease","text":["neurological dysfunction"],"offsets":[[218,242]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"10690","type":"Chemical","text":["dexamethasone"],"offsets":[[297,310]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"10691","type":"Chemical","text":["dexamethasone"],"offsets":[[380,393]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"10692","type":"Chemical","text":["dexamethasone"],"offsets":[[440,453]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"10693","type":"Chemical","text":["Dexamethasone"],"offsets":[[509,522]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"10694","type":"Disease","text":["asphyxia"],"offsets":[[649,657]],"normalized":[{"db_name":"MESH","db_id":"D001237"}]},{"id":"10695","type":"Disease","text":["malformations"],"offsets":[[659,672]],"normalized":[{"db_name":"MESH","db_id":"D000014"}]},{"id":"10696","type":"Disease","text":["haemorrhage"],"offsets":[[748,759]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"10697","type":"Disease","text":["periventricular leukomalacia"],"offsets":[[779,807]],"normalized":[{"db_name":"MESH","db_id":"D007969"}]},{"id":"10698","type":"Disease","text":["psychomotor retardation"],"offsets":[[820,843]],"normalized":[{"db_name":"MESH","db_id":"D011596"}]},{"id":"10699","type":"Disease","text":["neurological dysfunctions"],"offsets":[[902,927]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"10700","type":"Chemical","text":["dexamethasone"],"offsets":[[1460,1473]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"10701","type":"Disease","text":["neurological dysfunctions"],"offsets":[[1524,1549]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"10702","type":"Chemical","text":["dexamethasone"],"offsets":[[1712,1725]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]}],"events":[],"coreferences":[],"relations":[{"id":"10703","type":"CID","arg1_id":"10688","arg2_id":"10687","normalized":[]},{"id":"10704","type":"CID","arg1_id":"10688","arg2_id":"10689","normalized":[]},{"id":"10705","type":"CID","arg1_id":"10688","arg2_id":"10699","normalized":[]},{"id":"10706","type":"CID","arg1_id":"10688","arg2_id":"10701","normalized":[]},{"id":"10707","type":"CID","arg1_id":"10690","arg2_id":"10687","normalized":[]},{"id":"10708","type":"CID","arg1_id":"10690","arg2_id":"10689","normalized":[]},{"id":"10709","type":"CID","arg1_id":"10690","arg2_id":"10699","normalized":[]},{"id":"10710","type":"CID","arg1_id":"10690","arg2_id":"10701","normalized":[]},{"id":"10711","type":"CID","arg1_id":"10691","arg2_id":"10687","normalized":[]},{"id":"10712","type":"CID","arg1_id":"10691","arg2_id":"10689","normalized":[]},{"id":"10713","type":"CID","arg1_id":"10691","arg2_id":"10699","normalized":[]},{"id":"10714","type":"CID","arg1_id":"10691","arg2_id":"10701","normalized":[]},{"id":"10715","type":"CID","arg1_id":"10692","arg2_id":"10687","normalized":[]},{"id":"10716","type":"CID","arg1_id":"10692","arg2_id":"10689","normalized":[]},{"id":"10717","type":"CID","arg1_id":"10692","arg2_id":"10699","normalized":[]},{"id":"10718","type":"CID","arg1_id":"10692","arg2_id":"10701","normalized":[]},{"id":"10719","type":"CID","arg1_id":"10693","arg2_id":"10687","normalized":[]},{"id":"10720","type":"CID","arg1_id":"10693","arg2_id":"10689","normalized":[]},{"id":"10721","type":"CID","arg1_id":"10693","arg2_id":"10699","normalized":[]},{"id":"10722","type":"CID","arg1_id":"10693","arg2_id":"10701","normalized":[]},{"id":"10723","type":"CID","arg1_id":"10700","arg2_id":"10687","normalized":[]},{"id":"10724","type":"CID","arg1_id":"10700","arg2_id":"10689","normalized":[]},{"id":"10725","type":"CID","arg1_id":"10700","arg2_id":"10699","normalized":[]},{"id":"10726","type":"CID","arg1_id":"10700","arg2_id":"10701","normalized":[]},{"id":"10727","type":"CID","arg1_id":"10702","arg2_id":"10687","normalized":[]},{"id":"10728","type":"CID","arg1_id":"10702","arg2_id":"10689","normalized":[]},{"id":"10729","type":"CID","arg1_id":"10702","arg2_id":"10699","normalized":[]},{"id":"10730","type":"CID","arg1_id":"10702","arg2_id":"10701","normalized":[]}]}
{"id":"10731","document_id":"11912119","passages":[{"id":"10732","type":"title","text":["Force overflow and levodopa-induced dyskinesias in Parkinson's disease."],"offsets":[[0,71]]},{"id":"10733","type":"abstract","text":["We assessed force coordination of the hand in Parkinson's disease and its relationship to motor complications of levodopa therapy, particularly to levodopa-induced dyskinesias (LID). We studied two groups of Parkinson's disease patients with (Parkinson's disease + LID, n = 23) and without levodopa-induced dyskinesias (Parkinson's disease - LID, n = 10), and age-matched healthy controls. The motor score of the Unified Parkinson's Disease Rating Scale, a dyskinesia score and force in a grip-lift paradigm were assessed ON and OFF levodopa. A pathological increase of forces was seen in ON-state in Parkinson's disease + LID only. In Parkinson's disease + LID, the force involved in pressing down the object before lifting was significantly increased by levodopa (by 61%, P < 0.05). An overshooting of peak grip force by 51% (P < 0.05) and of static grip force by 45% (P < 0.01) was observed in the ON- compared with the OFF-drug condition. In contrast, no excessive force was found in Parkinson's disease - LID. Peak grip force in ON-state was 140% (P < 0.05) higher in Parkinson's disease + LID than in Parkinson's disease - LID, while static grip force was increased by 138% (P < 0.01) between groups. Severity of peak-dose dyskinesias was strongly correlated with grip force in ON-state (r = 0.79 with peak force, P < 0.01). No correlation was observed between forces and the motor score as well as with the daily dose of dopaminergic medication. Force excess was only observed in patients with LID and motor fluctuations. A close relationship was seen between the overshooting of forces and dyskinesias in the ON-drug condition. We postulate that both LID and grip force excess share common pathophysiological mechanisms related to motor fluctuations."],"offsets":[[72,1830]]}],"entities":[{"id":"10734","type":"Chemical","text":["levodopa"],"offsets":[[19,27]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"10735","type":"Disease","text":["dyskinesias"],"offsets":[[36,47]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"10736","type":"Disease","text":["Parkinson's disease"],"offsets":[[51,70]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"10737","type":"Disease","text":["Parkinson's disease"],"offsets":[[118,137]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"10738","type":"Chemical","text":["levodopa"],"offsets":[[185,193]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"10739","type":"Chemical","text":["levodopa"],"offsets":[[219,227]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"10740","type":"Disease","text":["dyskinesias"],"offsets":[[236,247]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"10741","type":"Disease","text":["LID"],"offsets":[[249,252]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"10742","type":"Disease","text":["Parkinson's disease"],"offsets":[[280,299]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"10743","type":"Disease","text":["Parkinson's disease"],"offsets":[[315,334]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"10744","type":"Disease","text":["LID"],"offsets":[[337,340]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"10745","type":"Chemical","text":["levodopa"],"offsets":[[362,370]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"10746","type":"Disease","text":["dyskinesias"],"offsets":[[379,390]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"10747","type":"Disease","text":["Parkinson's disease"],"offsets":[[392,411]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"10748","type":"Disease","text":["LID"],"offsets":[[414,417]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"10749","type":"Disease","text":["Parkinson's 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{"id":"10863","document_id":"9105126","passages":[{"id":"10864","type":"title","text":["Postinfarction ventricular septal defect associated with long-term steroid therapy."],"offsets":[[0,83]]},{"id":"10865","type":"abstract","text":["Two cases of postinfarction ventricular septal rupture in patients on long-term steroid therapy are presented and the favourable outcome in both cases described. A possible association between steroid therapy and subsequent postinfarction septal rupture is discussed."],"offsets":[[84,351]]}],"entities":[{"id":"10866","type":"Disease","text":["ventricular septal defect"],"offsets":[[15,40]],"normalized":[{"db_name":"MESH","db_id":"D018658"}]},{"id":"10867","type":"Chemical","text":["steroid"],"offsets":[[67,74]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"10868","type":"Disease","text":["ventricular septal rupture"],"offsets":[[112,138]],"normalized":[{"db_name":"MESH","db_id":"D018658"}]},{"id":"10869","type":"Chemical","text":["steroid"],"offsets":[[164,171]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"10870","type":"Chemical","text":["steroid"],"offsets":[[277,284]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"10871","type":"Disease","text":["septal rupture"],"offsets":[[323,337]],"normalized":[{"db_name":"MESH","db_id":"D018658"}]}],"events":[],"coreferences":[],"relations":[{"id":"10872","type":"CID","arg1_id":"10867","arg2_id":"10866","normalized":[]},{"id":"10873","type":"CID","arg1_id":"10867","arg2_id":"10868","normalized":[]},{"id":"10874","type":"CID","arg1_id":"10867","arg2_id":"10871","normalized":[]},{"id":"10875","type":"CID","arg1_id":"10869","arg2_id":"10866","normalized":[]},{"id":"10876","type":"CID","arg1_id":"10869","arg2_id":"10868","normalized":[]},{"id":"10877","type":"CID","arg1_id":"10869","arg2_id":"10871","normalized":[]},{"id":"10878","type":"CID","arg1_id":"10870","arg2_id":"10866","normalized":[]},{"id":"10879","type":"CID","arg1_id":"10870","arg2_id":"10868","normalized":[]},{"id":"10880","type":"CID","arg1_id":"10870","arg2_id":"10871","normalized":[]}]}
{"id":"10881","document_id":"8599504","passages":[{"id":"10882","type":"title","text":["Angioedema associated with droperidol administration."],"offsets":[[0,53]]},{"id":"10883","type":"abstract","text":["Angioedema, also known as angioneurotic edema or Quincke's disease, is a well-demarcated, localized edema involving the subcutaneous tissues that may cause upper-airway obstruction. We report the case of a previously healthy 19-year-old man with no known drug allergies in whom angioedema with significant tongue swelling and protrusion developed within 10 minutes of the administration of a single IV dose of droperidol."],"offsets":[[54,475]]}],"entities":[{"id":"10884","type":"Disease","text":["Angioedema"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D000799"}]},{"id":"10885","type":"Chemical","text":["droperidol"],"offsets":[[27,37]],"normalized":[{"db_name":"MESH","db_id":"D004329"}]},{"id":"10886","type":"Disease","text":["Angioedema"],"offsets":[[54,64]],"normalized":[{"db_name":"MESH","db_id":"D000799"}]},{"id":"10887","type":"Disease","text":["angioneurotic edema"],"offsets":[[80,99]],"normalized":[{"db_name":"MESH","db_id":"D000799"}]},{"id":"10888","type":"Disease","text":["Quincke's disease"],"offsets":[[103,120]],"normalized":[{"db_name":"MESH","db_id":"D000799"}]},{"id":"10889","type":"Disease","text":["edema"],"offsets":[[154,159]],"normalized":[{"db_name":"MESH","db_id":"D004487"}]},{"id":"10890","type":"Disease","text":["upper-airway obstruction"],"offsets":[[210,234]],"normalized":[{"db_name":"MESH","db_id":"D000402"}]},{"id":"10891","type":"Disease","text":["drug allergies"],"offsets":[[309,323]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"10892","type":"Disease","text":["angioedema"],"offsets":[[332,342]],"normalized":[{"db_name":"MESH","db_id":"D000799"}]},{"id":"10893","type":"Disease","text":["tongue swelling"],"offsets":[[360,375]],"normalized":[{"db_name":"MESH","db_id":"D014060"},{"db_name":"MESH","db_id":"D004487"}]},{"id":"10894","type":"Disease","text":["tongue swelling"],"offsets":[[360,375]],"normalized":[{"db_name":"MESH","db_id":"D014060"}]},{"id":"10895","type":"Disease","text":["swelling"],"offsets":[[367,375]],"normalized":[{"db_name":"MESH","db_id":"D004487"}]},{"id":"10896","type":"Chemical","text":["droperidol"],"offsets":[[464,474]],"normalized":[{"db_name":"MESH","db_id":"D004329"}]}],"events":[],"coreferences":[],"relations":[{"id":"10897","type":"CID","arg1_id":"10885","arg2_id":"10884","normalized":[]},{"id":"10898","type":"CID","arg1_id":"10885","arg2_id":"10886","normalized":[]},{"id":"10899","type":"CID","arg1_id":"10885","arg2_id":"10887","normalized":[]},{"id":"10900","type":"CID","arg1_id":"10885","arg2_id":"10888","normalized":[]},{"id":"10901","type":"CID","arg1_id":"10885","arg2_id":"10892","normalized":[]},{"id":"10902","type":"CID","arg1_id":"10896","arg2_id":"10884","normalized":[]},{"id":"10903","type":"CID","arg1_id":"10896","arg2_id":"10886","normalized":[]},{"id":"10904","type":"CID","arg1_id":"10896","arg2_id":"10887","normalized":[]},{"id":"10905","type":"CID","arg1_id":"10896","arg2_id":"10888","normalized":[]},{"id":"10906","type":"CID","arg1_id":"10896","arg2_id":"10892","normalized":[]}]}
{"id":"10907","document_id":"8546130","passages":[{"id":"10908","type":"title","text":["Clarithromycin-associated visual hallucinations in a patient with chronic renal failure on continuous ambulatory peritoneal dialysis."],"offsets":[[0,133]]},{"id":"10909","type":"abstract","text":["Visual hallucinations are a rare event in chronic renal failure and not related to uremia per se. Unreported in the literature is visual hallucinations occurring in association with the new macrolide antibiotic, clarithromycin. We describe such a case in a patient with end-stage renal disease (ESRD) maintained on continuous ambulatory peritoneal dialysis (CAPD). The combination of a relatively high dose of clarithromycin in face of chronic renal failure in a functionally anephric patient, with underlying aluminum intoxication, may have facilitated the appearance of this neurotoxic side effect. It is important to understand the pharmacokinetics of medications in face of chronic renal failure, the possibility of drug interactions, and how these factors should help guide medication therapy in the ESRD patient."],"offsets":[[134,952]]}],"entities":[{"id":"10910","type":"Chemical","text":["Clarithromycin"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D017291"}]},{"id":"10911","type":"Disease","text":["visual hallucinations"],"offsets":[[26,47]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"10912","type":"Disease","text":["chronic renal failure"],"offsets":[[66,87]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"10913","type":"Disease","text":["Visual hallucinations"],"offsets":[[134,155]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"10914","type":"Disease","text":["chronic renal failure"],"offsets":[[176,197]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"10915","type":"Disease","text":["uremia"],"offsets":[[217,223]],"normalized":[{"db_name":"MESH","db_id":"D014511"}]},{"id":"10916","type":"Disease","text":["visual hallucinations"],"offsets":[[264,285]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"10917","type":"Chemical","text":["macrolide"],"offsets":[[324,333]],"normalized":[{"db_name":"MESH","db_id":"D018942"}]},{"id":"10918","type":"Chemical","text":["clarithromycin"],"offsets":[[346,360]],"normalized":[{"db_name":"MESH","db_id":"D017291"}]},{"id":"10919","type":"Disease","text":["end-stage renal disease"],"offsets":[[404,427]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"10920","type":"Disease","text":["ESRD"],"offsets":[[429,433]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"10921","type":"Chemical","text":["clarithromycin"],"offsets":[[544,558]],"normalized":[{"db_name":"MESH","db_id":"D017291"}]},{"id":"10922","type":"Disease","text":["chronic renal failure"],"offsets":[[570,591]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"10923","type":"Chemical","text":["aluminum"],"offsets":[[644,652]],"normalized":[{"db_name":"MESH","db_id":"D000535"}]},{"id":"10924","type":"Disease","text":["neurotoxic"],"offsets":[[711,721]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"10925","type":"Disease","text":["chronic renal failure"],"offsets":[[812,833]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]},{"id":"10926","type":"Disease","text":["ESRD"],"offsets":[[939,943]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]}],"events":[],"coreferences":[],"relations":[{"id":"10927","type":"CID","arg1_id":"10910","arg2_id":"10911","normalized":[]},{"id":"10928","type":"CID","arg1_id":"10910","arg2_id":"10913","normalized":[]},{"id":"10929","type":"CID","arg1_id":"10910","arg2_id":"10916","normalized":[]},{"id":"10930","type":"CID","arg1_id":"10918","arg2_id":"10911","normalized":[]},{"id":"10931","type":"CID","arg1_id":"10918","arg2_id":"10913","normalized":[]},{"id":"10932","type":"CID","arg1_id":"10918","arg2_id":"10916","normalized":[]},{"id":"10933","type":"CID","arg1_id":"10921","arg2_id":"10911","normalized":[]},{"id":"10934","type":"CID","arg1_id":"10921","arg2_id":"10913","normalized":[]},{"id":"10935","type":"CID","arg1_id":"10921","arg2_id":"10916","normalized":[]}]}
{"id":"10936","document_id":"7724492","passages":[{"id":"10937","type":"title","text":["Acute renal toxicity of doxorubicin (adriamycin)-loaded cyanoacrylate nanoparticles."],"offsets":[[0,84]]},{"id":"10938","type":"abstract","text":["Acute doxorubicin-loaded nanoparticle (DXNP) renal toxicity was explored in both normal rats and rats with experimental glomerulonephritis. In normal rats, 2\/6 rats given free doxorubicin (DX) (5 mg\/kg) died within one week, whereas all control animals and all rats having received free NP or DXNP survived. A 3 times higher proteinuria appeared in animals treated with DXNP than in those treated with DX. Free NP did not provoke any proteinuria. Two hr post-injection, DXNP was 2.7 times more concentrated in kidneys than free DX (p < 0.025). In rats with immune experimental glomerulonephritis, 5\/6 rats given DX died within 7 days, in contrast to animals treated by DXNP, NP, or untreated, which all survived. Proteinuria appeared in all series, but was 2-5 times more intense (p > 0.001) and prolonged after doxorubicin treatment (400-700 mg\/day), without significant difference between DXNP and DX. Rats treated by unloaded NP behaved as controls. These results demonstrate that, in these experimental conditions, DXNP killed less animals than free DX, despite of an enhanced renal toxicity of the former. Both effects (better survival and nephrosis) are most probably related to an enhanced capture of DXNP by cells of the mononuclear phagocyte system, including mesangial cells."],"offsets":[[85,1370]]}],"entities":[{"id":"10939","type":"Disease","text":["renal toxicity"],"offsets":[[6,20]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"10940","type":"Chemical","text":["doxorubicin"],"offsets":[[24,35]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"10941","type":"Chemical","text":["adriamycin"],"offsets":[[37,47]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"10942","type":"Chemical","text":["cyanoacrylate"],"offsets":[[56,69]],"normalized":[{"db_name":"MESH","db_id":"D003487"}]},{"id":"10943","type":"Chemical","text":["doxorubicin"],"offsets":[[91,102]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"10944","type":"Disease","text":["renal 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toxicity"],"offsets":[[1166,1180]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"10959","type":"Disease","text":["nephrosis"],"offsets":[[1230,1239]],"normalized":[{"db_name":"MESH","db_id":"D009401"}]}],"events":[],"coreferences":[],"relations":[{"id":"10960","type":"CID","arg1_id":"10940","arg2_id":"10948","normalized":[]},{"id":"10961","type":"CID","arg1_id":"10940","arg2_id":"10950","normalized":[]},{"id":"10962","type":"CID","arg1_id":"10940","arg2_id":"10954","normalized":[]},{"id":"10963","type":"CID","arg1_id":"10941","arg2_id":"10948","normalized":[]},{"id":"10964","type":"CID","arg1_id":"10941","arg2_id":"10950","normalized":[]},{"id":"10965","type":"CID","arg1_id":"10941","arg2_id":"10954","normalized":[]},{"id":"10966","type":"CID","arg1_id":"10943","arg2_id":"10948","normalized":[]},{"id":"10967","type":"CID","arg1_id":"10943","arg2_id":"10950","normalized":[]},{"id":"10968","type":"CID","arg1_id":"10943","arg2_id":"10954","normalized":[]},{"id":"10969","type":"CID","arg1_id":"10946","arg2_id":"10948","normalized":[]},{"id":"10970","type":"CID","arg1_id":"10946","arg2_id":"10950","normalized":[]},{"id":"10971","type":"CID","arg1_id":"10946","arg2_id":"10954","normalized":[]},{"id":"10972","type":"CID","arg1_id":"10947","arg2_id":"10948","normalized":[]},{"id":"10973","type":"CID","arg1_id":"10947","arg2_id":"10950","normalized":[]},{"id":"10974","type":"CID","arg1_id":"10947","arg2_id":"10954","normalized":[]},{"id":"10975","type":"CID","arg1_id":"10949","arg2_id":"10948","normalized":[]},{"id":"10976","type":"CID","arg1_id":"10949","arg2_id":"10950","normalized":[]},{"id":"10977","type":"CID","arg1_id":"10949","arg2_id":"10954","normalized":[]},{"id":"10978","type":"CID","arg1_id":"10951","arg2_id":"10948","normalized":[]},{"id":"10979","type":"CID","arg1_id":"10951","arg2_id":"10950","normalized":[]},{"id":"10980","type":"CID","arg1_id":"10951","arg2_id":"10954","normalized":[]},{"id":"10981","type":"CID","arg1_id":"10953","arg2_id":"10948","normalized":[]},{"id":"10982","type":"CID","arg1_id":"10953","arg2_id":"10950","normalized":[]},{"id":"10983","type":"CID","arg1_id":"10953","arg2_id":"10954","normalized":[]},{"id":"10984","type":"CID","arg1_id":"10955","arg2_id":"10948","normalized":[]},{"id":"10985","type":"CID","arg1_id":"10955","arg2_id":"10950","normalized":[]},{"id":"10986","type":"CID","arg1_id":"10955","arg2_id":"10954","normalized":[]},{"id":"10987","type":"CID","arg1_id":"10956","arg2_id":"10948","normalized":[]},{"id":"10988","type":"CID","arg1_id":"10956","arg2_id":"10950","normalized":[]},{"id":"10989","type":"CID","arg1_id":"10956","arg2_id":"10954","normalized":[]},{"id":"10990","type":"CID","arg1_id":"10957","arg2_id":"10948","normalized":[]},{"id":"10991","type":"CID","arg1_id":"10957","arg2_id":"10950","normalized":[]},{"id":"10992","type":"CID","arg1_id":"10957","arg2_id":"10954","normalized":[]}]}
{"id":"10993","document_id":"7619765","passages":[{"id":"10994","type":"title","text":["Etoposide-related myocardial infarction."],"offsets":[[0,40]]},{"id":"10995","type":"abstract","text":["The occurrence of a myocardial infarction is reported after chemotherapy containing etoposide, in a man with no risk factors for coronary heart disease. Possible causal mechanisms are discussed."],"offsets":[[41,235]]}],"entities":[{"id":"10996","type":"Chemical","text":["Etoposide"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D005047"}]},{"id":"10997","type":"Disease","text":["myocardial infarction"],"offsets":[[18,39]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"10998","type":"Disease","text":["myocardial infarction"],"offsets":[[61,82]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"10999","type":"Chemical","text":["etoposide"],"offsets":[[125,134]],"normalized":[{"db_name":"MESH","db_id":"D005047"}]},{"id":"11000","type":"Disease","text":["coronary heart disease"],"offsets":[[170,192]],"normalized":[{"db_name":"MESH","db_id":"D003327"}]}],"events":[],"coreferences":[],"relations":[{"id":"11001","type":"CID","arg1_id":"10996","arg2_id":"10997","normalized":[]},{"id":"11002","type":"CID","arg1_id":"10996","arg2_id":"10998","normalized":[]},{"id":"11003","type":"CID","arg1_id":"10999","arg2_id":"10997","normalized":[]},{"id":"11004","type":"CID","arg1_id":"10999","arg2_id":"10998","normalized":[]}]}
{"id":"11005","document_id":"7416947","passages":[{"id":"11006","type":"title","text":["Subjective assessment of sexual dysfunction of patients on long-term administration of digoxin."],"offsets":[[0,95]]},{"id":"11007","type":"abstract","text":["Various data suggest that male patients who have received digoxin on a longterm basis have increased levels of serum estrogen and decreased levels of plasma testosterone and luteinizing hormone (LH). This study was undertaken to investigate the links between the long-term administration of digoxin therapy and sexual behavior, and the effect of digoxin on plasma levels of estradiol, testosterone, and LH. The patients of the study and control group (without digoxin) were of similar cardiac functional capacity and age (25-40 years) and were randomly selected from the rheumatic heart disease patients. A subjective assessment of sexual behavior in the study and control groups was carried out, using parameters such as sexual desire, sexual excitement, and frequency of sexual relations. Personal interviews and a questionnaire were also used for the evaluation of sexual behavior. The findings support the reports concerning digoxin effect on plasma estradiol, testosterone, and LH. The differences in the means were significant. Tests used to evaluate the changes in sexual behavior showed a significant decrease in sexual desire, sexual excitement phase (erection), and frequency of sexual relations in the study group."],"offsets":[[96,1321]]}],"entities":[{"id":"11008","type":"Disease","text":["sexual dysfunction"],"offsets":[[25,43]],"normalized":[{"db_name":"MESH","db_id":"D020018"}]},{"id":"11009","type":"Chemical","text":["digoxin"],"offsets":[[87,94]],"normalized":[{"db_name":"MESH","db_id":"D004077"}]},{"id":"11010","type":"Chemical","text":["digoxin"],"offsets":[[154,161]],"normalized":[{"db_name":"MESH","db_id":"D004077"}]},{"id":"11011","type":"Chemical","text":["estrogen"],"offsets":[[213,221]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"11012","type":"Chemical","text":["testosterone"],"offsets":[[253,265]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"11013","type":"Chemical","text":["digoxin"],"offsets":[[387,394]],"normalized":[{"db_name":"MESH","db_id":"D004077"}]},{"id":"11014","type":"Chemical","text":["digoxin"],"offsets":[[442,449]],"normalized":[{"db_name":"MESH","db_id":"D004077"}]},{"id":"11015","type":"Chemical","text":["estradiol"],"offsets":[[470,479]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"11016","type":"Chemical","text":["testosterone"],"offsets":[[481,493]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"11017","type":"Chemical","text":["digoxin"],"offsets":[[556,563]],"normalized":[{"db_name":"MESH","db_id":"D004077"}]},{"id":"11018","type":"Disease","text":["rheumatic heart disease"],"offsets":[[667,690]],"normalized":[{"db_name":"MESH","db_id":"D012214"}]},{"id":"11019","type":"Chemical","text":["digoxin"],"offsets":[[1025,1032]],"normalized":[{"db_name":"MESH","db_id":"D004077"}]},{"id":"11020","type":"Chemical","text":["estradiol"],"offsets":[[1050,1059]],"normalized":[{"db_name":"MESH","db_id":"D004958"}]},{"id":"11021","type":"Chemical","text":["testosterone"],"offsets":[[1061,1073]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"11022","type":"Disease","text":["decrease in sexual desire"],"offsets":[[1205,1230]],"normalized":[{"db_name":"MESH","db_id":"D020018"}]}],"events":[],"coreferences":[],"relations":[{"id":"11023","type":"CID","arg1_id":"11009","arg2_id":"11008","normalized":[]},{"id":"11024","type":"CID","arg1_id":"11009","arg2_id":"11022","normalized":[]},{"id":"11025","type":"CID","arg1_id":"11010","arg2_id":"11008","normalized":[]},{"id":"11026","type":"CID","arg1_id":"11010","arg2_id":"11022","normalized":[]},{"id":"11027","type":"CID","arg1_id":"11013","arg2_id":"11008","normalized":[]},{"id":"11028","type":"CID","arg1_id":"11013","arg2_id":"11022","normalized":[]},{"id":"11029","type":"CID","arg1_id":"11014","arg2_id":"11008","normalized":[]},{"id":"11030","type":"CID","arg1_id":"11014","arg2_id":"11022","normalized":[]},{"id":"11031","type":"CID","arg1_id":"11017","arg2_id":"11008","normalized":[]},{"id":"11032","type":"CID","arg1_id":"11017","arg2_id":"11022","normalized":[]},{"id":"11033","type":"CID","arg1_id":"11019","arg2_id":"11008","normalized":[]},{"id":"11034","type":"CID","arg1_id":"11019","arg2_id":"11022","normalized":[]}]}
{"id":"11035","document_id":"7263204","passages":[{"id":"11036","type":"title","text":["Fatal aplastic anemia due to indomethacin--lymphocyte transformation tests in vitro."],"offsets":[[0,84]]},{"id":"11037","type":"abstract","text":["Although indomethacin has been implicated as a possible cause of aplastic anemia on the basis of a few clinical observations, its role has not been definitely established. A case of fatal aplastic anemia is described in which no drugs other than allopurinol and indomethacin were given. Indomethacin was first given four weeks prior to the onset of symptoms. A positive lymphocyte transformation test with indomethacin in vitro further substantiates the potential role of this drug in causing aplastic anemia in a susceptible patient. Fortunately, this seems to be a very rare complication."],"offsets":[[85,675]]}],"entities":[{"id":"11038","type":"Disease","text":["aplastic anemia"],"offsets":[[6,21]],"normalized":[{"db_name":"MESH","db_id":"D000741"}]},{"id":"11039","type":"Chemical","text":["indomethacin"],"offsets":[[29,41]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"11040","type":"Chemical","text":["indomethacin"],"offsets":[[94,106]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"11041","type":"Disease","text":["aplastic anemia"],"offsets":[[150,165]],"normalized":[{"db_name":"MESH","db_id":"D000741"}]},{"id":"11042","type":"Disease","text":["aplastic anemia"],"offsets":[[273,288]],"normalized":[{"db_name":"MESH","db_id":"D000741"}]},{"id":"11043","type":"Chemical","text":["allopurinol"],"offsets":[[331,342]],"normalized":[{"db_name":"MESH","db_id":"D000493"}]},{"id":"11044","type":"Chemical","text":["indomethacin"],"offsets":[[347,359]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"11045","type":"Chemical","text":["Indomethacin"],"offsets":[[372,384]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"11046","type":"Chemical","text":["indomethacin"],"offsets":[[491,503]],"normalized":[{"db_name":"MESH","db_id":"D007213"}]},{"id":"11047","type":"Disease","text":["aplastic anemia"],"offsets":[[578,593]],"normalized":[{"db_name":"MESH","db_id":"D000741"}]}],"events":[],"coreferences":[],"relations":[{"id":"11048","type":"CID","arg1_id":"11039","arg2_id":"11038","normalized":[]},{"id":"11049","type":"CID","arg1_id":"11039","arg2_id":"11041","normalized":[]},{"id":"11050","type":"CID","arg1_id":"11039","arg2_id":"11042","normalized":[]},{"id":"11051","type":"CID","arg1_id":"11039","arg2_id":"11047","normalized":[]},{"id":"11052","type":"CID","arg1_id":"11040","arg2_id":"11038","normalized":[]},{"id":"11053","type":"CID","arg1_id":"11040","arg2_id":"11041","normalized":[]},{"id":"11054","type":"CID","arg1_id":"11040","arg2_id":"11042","normalized":[]},{"id":"11055","type":"CID","arg1_id":"11040","arg2_id":"11047","normalized":[]},{"id":"11056","type":"CID","arg1_id":"11044","arg2_id":"11038","normalized":[]},{"id":"11057","type":"CID","arg1_id":"11044","arg2_id":"11041","normalized":[]},{"id":"11058","type":"CID","arg1_id":"11044","arg2_id":"11042","normalized":[]},{"id":"11059","type":"CID","arg1_id":"11044","arg2_id":"11047","normalized":[]},{"id":"11060","type":"CID","arg1_id":"11045","arg2_id":"11038","normalized":[]},{"id":"11061","type":"CID","arg1_id":"11045","arg2_id":"11041","normalized":[]},{"id":"11062","type":"CID","arg1_id":"11045","arg2_id":"11042","normalized":[]},{"id":"11063","type":"CID","arg1_id":"11045","arg2_id":"11047","normalized":[]},{"id":"11064","type":"CID","arg1_id":"11046","arg2_id":"11038","normalized":[]},{"id":"11065","type":"CID","arg1_id":"11046","arg2_id":"11041","normalized":[]},{"id":"11066","type":"CID","arg1_id":"11046","arg2_id":"11042","normalized":[]},{"id":"11067","type":"CID","arg1_id":"11046","arg2_id":"11047","normalized":[]}]}
{"id":"11068","document_id":"7066357","passages":[{"id":"11069","type":"title","text":["Plasma and urinary lipids and lipoproteins during the development of nephrotic syndrome induced in the rat by puromycin aminonucleoside."],"offsets":[[0,136]]},{"id":"11070","type":"abstract","text":["This study was undertaken to ascertain whether the alterations of plasma lipoproteins found in nephrotic syndrome induced by puromycin aminonucleoside were due to nephrotic syndrome per se, or, at least in part, to the aminonucleoside. The purpose of the present study was to investigate the changes in plasma and urinary lipoproteins during the administration of puromycin aminonucleoside (20 mg\/kg for 7 days) and the subsequent development of nephrotic syndrome. Since massive albuminuria occurred after 6 days of treatment, the time-course study was divided into two stages: pre-nephrotic stage (day 1-5) and nephrotic stage (day 6-11). In pre-nephrotic stage the plasma level of fatty acids, triacylglycerol and VLDL decreased while that of phospholipid, cholesteryl esters and HDL remained constant. Plasma apolipoprotein A-I tended to increase (40% increase at day 5). At the beginning of nephrotic stage (day 6) the concentration of plasma albumin dropped to a very low level, while that of apolipoprotein A-I increased abruptly (4-fold increase) and continued to rise, although less steeply, in the following days. The plasma concentration of HDL followed the same pattern. Plasma VLDL and LDL increased at a later stage (day 9). Plasma apolipoprotein A-I was found not only in HDL (1.063-1.210 g\/ml) but also in the LDL density class (1.025-1.050 g\/ml). In the pre-nephrotic stage lipoproteinuria was negligible, while in the early nephrotic stage the urinary loss of plasma lipoproteins consisted mainly of HDL. These observations indicate that puromycin aminonucleoside alters plasma lipoproteins by lowering VLDL and increasing HDL. It is likely that the early and striking increase of plasma HDL found in nephrotic rats is related to a direct effect of the drug on HDL metabolism."],"offsets":[[137,1931]]}],"entities":[{"id":"11071","type":"Disease","text":["nephrotic syndrome"],"offsets":[[69,87]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]},{"id":"11072","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[110,135]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"11073","type":"Disease","text":["nephrotic syndrome"],"offsets":[[232,250]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]},{"id":"11074","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[262,287]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"11075","type":"Disease","text":["nephrotic 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aminonucleoside"],"offsets":[[1693,1718]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"11090","type":"Disease","text":["nephrotic"],"offsets":[[1856,1865]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]}],"events":[],"coreferences":[],"relations":[{"id":"11091","type":"CID","arg1_id":"11072","arg2_id":"11071","normalized":[]},{"id":"11092","type":"CID","arg1_id":"11072","arg2_id":"11073","normalized":[]},{"id":"11093","type":"CID","arg1_id":"11072","arg2_id":"11075","normalized":[]},{"id":"11094","type":"CID","arg1_id":"11072","arg2_id":"11078","normalized":[]},{"id":"11095","type":"CID","arg1_id":"11072","arg2_id":"11080","normalized":[]},{"id":"11096","type":"CID","arg1_id":"11072","arg2_id":"11081","normalized":[]},{"id":"11097","type":"CID","arg1_id":"11072","arg2_id":"11082","normalized":[]},{"id":"11098","type":"CID","arg1_id":"11072","arg2_id":"11086","normalized":[]},{"id":"11099","type":"CID","arg1_id":"11072","arg2_id":"11087","normalized":[]},{"id":"11100","type":"CID","arg1_id":"11072","arg2_id":"11088","normalized":[]},{"id":"11101","type":"CID","arg1_id":"11072","arg2_id":"11090","normalized":[]},{"id":"11102","type":"CID","arg1_id":"11074","arg2_id":"11071","normalized":[]},{"id":"11103","type":"CID","arg1_id":"11074","arg2_id":"11073","normalized":[]},{"id":"11104","type":"CID","arg1_id":"11074","arg2_id":"11075","normalized":[]},{"id":"11105","type":"CID","arg1_id":"11074","arg2_id":"11078","normalized":[]},{"id":"11106","type":"CID","arg1_id":"11074","arg2_id":"11080","normalized":[]},{"id":"11107","type":"CID","arg1_id":"11074","arg2_id":"11081","normalized":[]},{"id":"11108","type":"CID","arg1_id":"11074","arg2_id":"11082","normalized":[]},{"id":"11109","type":"CID","arg1_id":"11074","arg2_id":"11086","normalized":[]},{"id":"11110","type":"CID","arg1_id":"11074","arg2_id":"11087","normalized":[]},{"id":"11111","type":"CID","arg1_id":"11074","arg2_id":"11088","normalized":[]},{"id":"11112","type":"CID","arg1_id":"11074","arg2_id":"11090","normalized":[]},{"id":"11113","type":"CID","arg1_id":"11076","arg2_id":"11071","normalized":[]},{"id":"11114","type":"CID","arg1_id":"11076","arg2_id":"11073","normalized":[]},{"id":"11115","type":"CID","arg1_id":"11076","arg2_id":"11075","normalized":[]},{"id":"11116","type":"CID","arg1_id":"11076","arg2_id":"11078","normalized":[]},{"id":"11117","type":"CID","arg1_id":"11076","arg2_id":"11080","normalized":[]},{"id":"11118","type":"CID","arg1_id":"11076","arg2_id":"11081","normalized":[]},{"id":"11119","type":"CID","arg1_id":"11076","arg2_id":"11082","normalized":[]},{"id":"11120","type":"CID","arg1_id":"11076","arg2_id":"11086","normalized":[]},{"id":"11121","type":"CID","arg1_id":"11076","arg2_id":"11087","normalized":[]},{"id":"11122","type":"CID","arg1_id":"11076","arg2_id":"11088","normalized":[]},{"id":"11123","type":"CID","arg1_id":"11076","arg2_id":"11090","normalized":[]},{"id":"11124","type":"CID","arg1_id":"11077","arg2_id":"11071","normalized":[]},{"id":"11125","type":"CID","arg1_id":"11077","arg2_id":"11073","normalized":[]},{"id":"11126","type":"CID","arg1_id":"11077","arg2_id":"11075","normalized":[]},{"id":"11127","type":"CID","arg1_id":"11077","arg2_id":"11078","normalized":[]},{"id":"11128","type":"CID","arg1_id":"11077","arg2_id":"11080","normalized":[]},{"id":"11129","type":"CID","arg1_id":"11077","arg2_id":"11081","normalized":[]},{"id":"11130","type":"CID","arg1_id":"11077","arg2_id":"11082","normalized":[]},{"id":"11131","type":"CID","arg1_id":"11077","arg2_id":"11086","normalized":[]},{"id":"11132","type":"CID","arg1_id":"11077","arg2_id":"11087","normalized":[]},{"id":"11133","type":"CID","arg1_id":"11077","arg2_id":"11088","normalized":[]},{"id":"11134","type":"CID","arg1_id":"11077","arg2_id":"11090","normalized":[]},{"id":"11135","type":"CID","arg1_id":"11089","arg2_id":"11071","normalized":[]},{"id":"11136","type":"CID","arg1_id":"11089","arg2_id":"11073","normalized":[]},{"id":"11137","type":"CID","arg1_id":"11089","arg2_id":"11075","normalized":[]},{"id":"11138","type":"CID","arg1_id":"11089","arg2_id":"11078","normalized":[]},{"id":"11139","type":"CID","arg1_id":"11089","arg2_id":"11080","normalized":[]},{"id":"11140","type":"CID","arg1_id":"11089","arg2_id":"11081","normalized":[]},{"id":"11141","type":"CID","arg1_id":"11089","arg2_id":"11082","normalized":[]},{"id":"11142","type":"CID","arg1_id":"11089","arg2_id":"11086","normalized":[]},{"id":"11143","type":"CID","arg1_id":"11089","arg2_id":"11087","normalized":[]},{"id":"11144","type":"CID","arg1_id":"11089","arg2_id":"11088","normalized":[]},{"id":"11145","type":"CID","arg1_id":"11089","arg2_id":"11090","normalized":[]}]}
{"id":"11146","document_id":"7007443","passages":[{"id":"11147","type":"title","text":["Circulating lysosomal enzymes and acute hepatic necrosis."],"offsets":[[0,57]]},{"id":"11148","type":"abstract","text":["The activities of the lysosomal enzymes acid and neutral protease, N-acetylglucosaminidase, and acid phosphatase were measured in the serum of patients with fulminant hepatic failure. Acid protease (cathepsin D) activity was increased about tenfold in patients who died and nearly fourfold in those who survived fulminant hepatic failure after paracetamol overdose, whereas activities were increased equally in patients with fulminant hepatic failure due to viral hepatitis whether or not they survived. A correlation was found between serum acid protease activity and prothrombin time, and the increase in cathepsin D activity was sustained over several days compared with aspartate aminotransferase, which showed a sharp early peak and then a fall. Circulating lysosomal proteases can damage other organs, and measurement of their activity may therefore be of added value in assessing prognosis in this condition."],"offsets":[[58,973]]}],"entities":[{"id":"11149","type":"Disease","text":["acute hepatic necrosis"],"offsets":[[34,56]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"11150","type":"Disease","text":["fulminant hepatic failure"],"offsets":[[215,240]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"11151","type":"Disease","text":["fulminant hepatic failure"],"offsets":[[370,395]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"11152","type":"Chemical","text":["paracetamol"],"offsets":[[402,413]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"11153","type":"Disease","text":["overdose"],"offsets":[[414,422]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"11154","type":"Disease","text":["fulminant hepatic failure"],"offsets":[[483,508]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"11155","type":"Disease","text":["viral hepatitis"],"offsets":[[516,531]],"normalized":[{"db_name":"MESH","db_id":"D006525"}]},{"id":"11156","type":"Chemical","text":["aspartate"],"offsets":[[732,741]],"normalized":[{"db_name":"MESH","db_id":"D001224"}]}],"events":[],"coreferences":[],"relations":[{"id":"11157","type":"CID","arg1_id":"11152","arg2_id":"11149","normalized":[]},{"id":"11158","type":"CID","arg1_id":"11152","arg2_id":"11150","normalized":[]},{"id":"11159","type":"CID","arg1_id":"11152","arg2_id":"11151","normalized":[]},{"id":"11160","type":"CID","arg1_id":"11152","arg2_id":"11154","normalized":[]}]}
{"id":"11161","document_id":"3762968","passages":[{"id":"11162","type":"title","text":["Transketolase abnormality in tolazamide-induced Wernicke's encephalopathy."],"offsets":[[0,74]]},{"id":"11163","type":"abstract","text":["We studied a thiamine-dependent enzyme, transketolase, from fibroblasts of a diabetic patient who developed Wernicke's encephalopathy when treated with tolazamide, in order to delineate if this patient also had transketolase abnormality [high Km for thiamine pyrophosphate (TPP)], as previously reported in postalcoholic Wernicke-Korsakoff syndrome. In addition to this patient, we also studied this enzyme from three diabetic kindreds without any history of Wernicke's encephalopathy and from four normal controls. We found that the above-mentioned patient and one of the diabetic kindreds with no history of Wernicke's encephalopathy had abnormal transketolase as determined by its Km for TPP. These data suggest a similarity between postalcoholic Wernicke-Korsakoff syndrome and the patient with tolazamide-induced Wernicke's encephalopathy from the standpoint of transketolase abnormality."],"offsets":[[75,968]]}],"entities":[{"id":"11164","type":"Chemical","text":["tolazamide"],"offsets":[[29,39]],"normalized":[{"db_name":"MESH","db_id":"D014042"}]},{"id":"11165","type":"Disease","text":["Wernicke's encephalopathy"],"offsets":[[48,73]],"normalized":[{"db_name":"MESH","db_id":"D014899"}]},{"id":"11166","type":"Chemical","text":["thiamine"],"offsets":[[88,96]],"normalized":[{"db_name":"MESH","db_id":"D013831"}]},{"id":"11167","type":"Disease","text":["diabetic"],"offsets":[[152,160]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"11168","type":"Disease","text":["Wernicke's encephalopathy"],"offsets":[[183,208]],"normalized":[{"db_name":"MESH","db_id":"D014899"}]},{"id":"11169","type":"Chemical","text":["tolazamide"],"offsets":[[227,237]],"normalized":[{"db_name":"MESH","db_id":"D014042"}]},{"id":"11170","type":"Chemical","text":["thiamine pyrophosphate"],"offsets":[[325,347]],"normalized":[{"db_name":"MESH","db_id":"D013835"}]},{"id":"11171","type":"Chemical","text":["TPP"],"offsets":[[349,352]],"normalized":[{"db_name":"MESH","db_id":"D013835"}]},{"id":"11172","type":"Disease","text":["Wernicke-Korsakoff syndrome"],"offsets":[[396,423]],"normalized":[{"db_name":"MESH","db_id":"D020915"}]},{"id":"11173","type":"Disease","text":["diabetic"],"offsets":[[493,501]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"11174","type":"Disease","text":["Wernicke's encephalopathy"],"offsets":[[534,559]],"normalized":[{"db_name":"MESH","db_id":"D014899"}]},{"id":"11175","type":"Disease","text":["diabetic"],"offsets":[[648,656]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"11176","type":"Disease","text":["Wernicke's encephalopathy"],"offsets":[[685,710]],"normalized":[{"db_name":"MESH","db_id":"D014899"}]},{"id":"11177","type":"Chemical","text":["TPP"],"offsets":[[766,769]],"normalized":[{"db_name":"MESH","db_id":"D013835"}]},{"id":"11178","type":"Disease","text":["Wernicke-Korsakoff syndrome"],"offsets":[[825,852]],"normalized":[{"db_name":"MESH","db_id":"D020915"}]},{"id":"11179","type":"Chemical","text":["tolazamide"],"offsets":[[874,884]],"normalized":[{"db_name":"MESH","db_id":"D014042"}]},{"id":"11180","type":"Disease","text":["Wernicke's encephalopathy"],"offsets":[[893,918]],"normalized":[{"db_name":"MESH","db_id":"D014899"}]}],"events":[],"coreferences":[],"relations":[{"id":"11181","type":"CID","arg1_id":"11164","arg2_id":"11165","normalized":[]},{"id":"11182","type":"CID","arg1_id":"11164","arg2_id":"11168","normalized":[]},{"id":"11183","type":"CID","arg1_id":"11164","arg2_id":"11174","normalized":[]},{"id":"11184","type":"CID","arg1_id":"11164","arg2_id":"11176","normalized":[]},{"id":"11185","type":"CID","arg1_id":"11164","arg2_id":"11180","normalized":[]},{"id":"11186","type":"CID","arg1_id":"11169","arg2_id":"11165","normalized":[]},{"id":"11187","type":"CID","arg1_id":"11169","arg2_id":"11168","normalized":[]},{"id":"11188","type":"CID","arg1_id":"11169","arg2_id":"11174","normalized":[]},{"id":"11189","type":"CID","arg1_id":"11169","arg2_id":"11176","normalized":[]},{"id":"11190","type":"CID","arg1_id":"11169","arg2_id":"11180","normalized":[]},{"id":"11191","type":"CID","arg1_id":"11179","arg2_id":"11165","normalized":[]},{"id":"11192","type":"CID","arg1_id":"11179","arg2_id":"11168","normalized":[]},{"id":"11193","type":"CID","arg1_id":"11179","arg2_id":"11174","normalized":[]},{"id":"11194","type":"CID","arg1_id":"11179","arg2_id":"11176","normalized":[]},{"id":"11195","type":"CID","arg1_id":"11179","arg2_id":"11180","normalized":[]}]}
{"id":"11196","document_id":"3413271","passages":[{"id":"11197","type":"title","text":["Mechanisms of myocardial ischemia induced by epinephrine: comparison with exercise-induced ischemia."],"offsets":[[0,100]]},{"id":"11198","type":"abstract","text":["The role of epinephrine in eliciting myocardial ischemia was examined in patients with coronary artery disease. Objective signs of ischemia and factors increasing myocardial oxygen consumption were compared during epinephrine infusion and supine bicycle exercise. Both epinephrine and exercise produced myocardial ischemia as evidenced by ST segment depression and angina. However, the mechanisms of myocardial ischemia induced by epinephrine were significantly different from those of exercise. Exercise-induced myocardial ischemia was marked predominantly by increased heart rate and rate-pressure product with a minor contribution of end-diastolic volume, while epinephrine-induced ischemia was characterized by a marked increase in contractility and a less pronounced increase in heart rate and rate-pressure product. These findings indicate that ischemia produced by epinephrine, as may occur during states of emotional distress, has a mechanism distinct from that due to physical exertion."],"offsets":[[101,1096]]}],"entities":[{"id":"11199","type":"Disease","text":["myocardial ischemia"],"offsets":[[14,33]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"11200","type":"Chemical","text":["epinephrine"],"offsets":[[45,56]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"11201","type":"Disease","text":["ischemia"],"offsets":[[91,99]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"11202","type":"Chemical","text":["epinephrine"],"offsets":[[113,124]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"11203","type":"Disease","text":["myocardial ischemia"],"offsets":[[138,157]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"11204","type":"Disease","text":["coronary artery 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ischemia"],"offsets":[[404,423]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"11210","type":"Disease","text":["depression"],"offsets":[[451,461]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"11211","type":"Disease","text":["angina"],"offsets":[[466,472]],"normalized":[{"db_name":"MESH","db_id":"D000787"}]},{"id":"11212","type":"Disease","text":["myocardial ischemia"],"offsets":[[501,520]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"11213","type":"Chemical","text":["epinephrine"],"offsets":[[532,543]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"11214","type":"Disease","text":["myocardial ischemia"],"offsets":[[614,633]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"11215","type":"Chemical","text":["epinephrine"],"offsets":[[766,777]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"11216","type":"Disease","text":["ischemia"],"offsets":[[786,794]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"11217","type":"Disease","text":["ischemia"],"offsets":[[952,960]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"11218","type":"Chemical","text":["epinephrine"],"offsets":[[973,984]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]}],"events":[],"coreferences":[],"relations":[{"id":"11219","type":"CID","arg1_id":"11200","arg2_id":"11199","normalized":[]},{"id":"11220","type":"CID","arg1_id":"11200","arg2_id":"11203","normalized":[]},{"id":"11221","type":"CID","arg1_id":"11200","arg2_id":"11209","normalized":[]},{"id":"11222","type":"CID","arg1_id":"11200","arg2_id":"11212","normalized":[]},{"id":"11223","type":"CID","arg1_id":"11200","arg2_id":"11214","normalized":[]},{"id":"11224","type":"CID","arg1_id":"11202","arg2_id":"11199","normalized":[]},{"id":"11225","type":"CID","arg1_id":"11202","arg2_id":"11203","normalized":[]},{"id":"11226","type":"CID","arg1_id":"11202","arg2_id":"11209","normalized":[]},{"id":"11227","type":"CID","arg1_id":"11202","arg2_id":"11212","normalized":[]},{"id":"11228","type":"CID","arg1_id":"11202","arg2_id":"11214","normalized":[]},{"id":"11229","type":"CID","arg1_id":"11207","arg2_id":"11199","normalized":[]},{"id":"11230","type":"CID","arg1_id":"11207","arg2_id":"11203","normalized":[]},{"id":"11231","type":"CID","arg1_id":"11207","arg2_id":"11209","normalized":[]},{"id":"11232","type":"CID","arg1_id":"11207","arg2_id":"11212","normalized":[]},{"id":"11233","type":"CID","arg1_id":"11207","arg2_id":"11214","normalized":[]},{"id":"11234","type":"CID","arg1_id":"11208","arg2_id":"11199","normalized":[]},{"id":"11235","type":"CID","arg1_id":"11208","arg2_id":"11203","normalized":[]},{"id":"11236","type":"CID","arg1_id":"11208","arg2_id":"11209","normalized":[]},{"id":"11237","type":"CID","arg1_id":"11208","arg2_id":"11212","normalized":[]},{"id":"11238","type":"CID","arg1_id":"11208","arg2_id":"11214","normalized":[]},{"id":"11239","type":"CID","arg1_id":"11213","arg2_id":"11199","normalized":[]},{"id":"11240","type":"CID","arg1_id":"11213","arg2_id":"11203","normalized":[]},{"id":"11241","type":"CID","arg1_id":"11213","arg2_id":"11209","normalized":[]},{"id":"11242","type":"CID","arg1_id":"11213","arg2_id":"11212","normalized":[]},{"id":"11243","type":"CID","arg1_id":"11213","arg2_id":"11214","normalized":[]},{"id":"11244","type":"CID","arg1_id":"11215","arg2_id":"11199","normalized":[]},{"id":"11245","type":"CID","arg1_id":"11215","arg2_id":"11203","normalized":[]},{"id":"11246","type":"CID","arg1_id":"11215","arg2_id":"11209","normalized":[]},{"id":"11247","type":"CID","arg1_id":"11215","arg2_id":"11212","normalized":[]},{"id":"11248","type":"CID","arg1_id":"11215","arg2_id":"11214","normalized":[]},{"id":"11249","type":"CID","arg1_id":"11218","arg2_id":"11199","normalized":[]},{"id":"11250","type":"CID","arg1_id":"11218","arg2_id":"11203","normalized":[]},{"id":"11251","type":"CID","arg1_id":"11218","arg2_id":"11209","normalized":[]},{"id":"11252","type":"CID","arg1_id":"11218","arg2_id":"11212","normalized":[]},{"id":"11253","type":"CID","arg1_id":"11218","arg2_id":"11214","normalized":[]}]}
{"id":"11254","document_id":"3088349","passages":[{"id":"11255","type":"title","text":["Transient contralateral rotation following unilateral substantia nigra lesion reflects susceptibility of the nigrostriatal system to exhaustion by amphetamine."],"offsets":[[0,159]]},{"id":"11256","type":"abstract","text":["Following unilateral 6-OHDA induced SN lesion, a transient period of contralateral rotation has been reported to precede the predominant ipsilateral circling. In order to clarify the nature of this initial contralateral rotation we examined the effect of the duration of recovery period after the lesion, on amphetamine-induced rotational behavior. Three days post lesion, most rats circled predominantly contralaterally to the lesion. Such contralateral rotation may result from either degeneration-induced breakdown of the DA pool, or lesion-induced increase of DA turnover in the spared neurons. A substantial degree of contralateral preference was still evident when amphetamine was administered for the first time 24 days after lesioning, indicating involvement of spared cells in the contralateral rotation. However, regardless of the duration of recovery (and irrespective of either lesion volume, amphetamine dose, or post-lesion motor exercise), amphetamine-induced rotation tended to become gradually more ipsilateral as the observation session progressed, and all rats circled ipsilaterally to the lesion in response to further amphetamine injections. These findings suggest that amphetamine has an irreversible effect on the post-lesion DA pool contributing to contralateral rotation."],"offsets":[[160,1456]]}],"entities":[{"id":"11257","type":"Disease","text":["contralateral rotation"],"offsets":[[10,32]],"normalized":[{"db_name":"MESH","db_id":"D009069"}]},{"id":"11258","type":"Disease","text":["substantia nigra lesion"],"offsets":[[54,77]],"normalized":[]},{"id":"11259","type":"Chemical","text":["amphetamine"],"offsets":[[147,158]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"11260","type":"Chemical","text":["6-OHDA"],"offsets":[[181,187]],"normalized":[{"db_name":"MESH","db_id":"D016627"}]},{"id":"11261","type":"Disease","text":["SN lesion"],"offsets":[[196,205]],"normalized":[]},{"id":"11262","type":"Disease","text":["contralateral rotation"],"offsets":[[229,251]],"normalized":[{"db_name":"MESH","db_id":"D009069"}]},{"id":"11263","type":"Disease","text":["ipsilateral 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{"id":"11339","document_id":"3001299","passages":[{"id":"11340","type":"title","text":["Thyroid function and urine-concentrating ability during lithium treatment."],"offsets":[[0,74]]},{"id":"11341","type":"abstract","text":["It has been suggested that adenylate cyclase inhibition may be important in the development of both nephrogenic diabetes insipidus and hypothyroidism during lithium treatment. We measured serum thyroxine and urine-concentrating ability (Umax) in response to desmopressin (DDAVP) in 85 patients receiving lithium. Hypothyroidism developed in eight patients while they were taking lithium. Impaired Umax was found in both euthyroid and hypothyroid patients while some hypothyroid patients concentrated their urine well. It is concluded that the dominant mechanisms by which lithium exerts these two effects are different."],"offsets":[[75,694]]}],"entities":[{"id":"11342","type":"Chemical","text":["lithium"],"offsets":[[56,63]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"11343","type":"Disease","text":["nephrogenic diabetes insipidus"],"offsets":[[175,205]],"normalized":[{"db_name":"MESH","db_id":"D018500"}]},{"id":"11344","type":"Disease","text":["hypothyroidism"],"offsets":[[210,224]],"normalized":[{"db_name":"MESH","db_id":"D007037"}]},{"id":"11345","type":"Chemical","text":["lithium"],"offsets":[[232,239]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"11346","type":"Chemical","text":["thyroxine"],"offsets":[[269,278]],"normalized":[{"db_name":"MESH","db_id":"D013974"}]},{"id":"11347","type":"Chemical","text":["lithium"],"offsets":[[379,386]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"11348","type":"Disease","text":["Hypothyroidism"],"offsets":[[388,402]],"normalized":[{"db_name":"MESH","db_id":"D007037"}]},{"id":"11349","type":"Chemical","text":["lithium"],"offsets":[[454,461]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"11350","type":"Disease","text":["hypothyroid"],"offsets":[[509,520]],"normalized":[{"db_name":"MESH","db_id":"D007037"}]},{"id":"11351","type":"Disease","text":["hypothyroid"],"offsets":[[541,552]],"normalized":[{"db_name":"MESH","db_id":"D007037"}]},{"id":"11352","type":"Chemical","text":["lithium"],"offsets":[[647,654]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]}],"events":[],"coreferences":[],"relations":[{"id":"11353","type":"CID","arg1_id":"11342","arg2_id":"11344","normalized":[]},{"id":"11354","type":"CID","arg1_id":"11342","arg2_id":"11348","normalized":[]},{"id":"11355","type":"CID","arg1_id":"11342","arg2_id":"11350","normalized":[]},{"id":"11356","type":"CID","arg1_id":"11342","arg2_id":"11351","normalized":[]},{"id":"11357","type":"CID","arg1_id":"11345","arg2_id":"11344","normalized":[]},{"id":"11358","type":"CID","arg1_id":"11345","arg2_id":"11348","normalized":[]},{"id":"11359","type":"CID","arg1_id":"11345","arg2_id":"11350","normalized":[]},{"id":"11360","type":"CID","arg1_id":"11345","arg2_id":"11351","normalized":[]},{"id":"11361","type":"CID","arg1_id":"11347","arg2_id":"11344","normalized":[]},{"id":"11362","type":"CID","arg1_id":"11347","arg2_id":"11348","normalized":[]},{"id":"11363","type":"CID","arg1_id":"11347","arg2_id":"11350","normalized":[]},{"id":"11364","type":"CID","arg1_id":"11347","arg2_id":"11351","normalized":[]},{"id":"11365","type":"CID","arg1_id":"11349","arg2_id":"11344","normalized":[]},{"id":"11366","type":"CID","arg1_id":"11349","arg2_id":"11348","normalized":[]},{"id":"11367","type":"CID","arg1_id":"11349","arg2_id":"11350","normalized":[]},{"id":"11368","type":"CID","arg1_id":"11349","arg2_id":"11351","normalized":[]},{"id":"11369","type":"CID","arg1_id":"11352","arg2_id":"11344","normalized":[]},{"id":"11370","type":"CID","arg1_id":"11352","arg2_id":"11348","normalized":[]},{"id":"11371","type":"CID","arg1_id":"11352","arg2_id":"11350","normalized":[]},{"id":"11372","type":"CID","arg1_id":"11352","arg2_id":"11351","normalized":[]}]}
{"id":"11373","document_id":"2004015","passages":[{"id":"11374","type":"title","text":["Sensitivity of erythroid progenitor colonies to erythropoietin in azidothymidine treated immunodeficient mice."],"offsets":[[0,110]]},{"id":"11375","type":"abstract","text":["The anaemia induced by 3'-azido-3'dideoxythymidine (AZT) is poorly understood. We have used a murine model of AIDS, infection of female C57BL\/6 mice with LP-BM5 murine leukaemia (MuLV) virus, to determine if AZT-induced anaemia is due, in part, to decreased responsiveness of erythropoietic precursors (BFU-e) to erythropoietin (EPO). Mice in the early stage of LP-BM5 MuLV disease were given AZT in their drinking water at 1.0 and 2.5 mg\/ml. AZT produced anaemia in both groups, in a dose-dependent fashion. Despite the anaemia, the number of splenic and bone marrow BFU-e in AZT treated mice increased up to five-fold over levels observed in infected untreated animals after 15 d of treatment. Colony formation by splenic and bone marrow BFUe was stimulated at lower concentrations of EPO in mice receiving AZT for 15 d than for infected, untreated mice. By day 30, sensitivity of both splenic and bone marrow BFU-e of treated animals returned to that observed from cells of infected untreated animals. The mean plasma levels of EPO observed in AZT treated mice were appropriate for the degree of anaemia observed when compared with phenylhydrazine (PHZ) treated mice. The numbers of BFU-e and the percentage of bone marrow erythroblasts observed were comparable in AZT and PHZ treated mice with similar degrees of anaemia. However, reticulocytosis was inappropriate for the degree of anaemia observed in AZT treated infected mice. AZT-induced peripheral anaemia in the face of increased numbers of BFU-e and increased levels of plasma EPO suggest a lesion in terminal differentiation."],"offsets":[[111,1698]]}],"entities":[{"id":"11376","type":"Chemical","text":["azidothymidine"],"offsets":[[66,80]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"11377","type":"Disease","text":["immunodeficient"],"offsets":[[89,104]],"normalized":[{"db_name":"MESH","db_id":"C565469"}]},{"id":"11378","type":"Disease","text":["anaemia"],"offsets":[[115,122]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"11379","type":"Chemical","text":["3'-azido-3'dideoxythymidine"],"offsets":[[134,161]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"11380","type":"Chemical","text":["AZT"],"offsets":[[163,166]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"11381","type":"Disease","text":["AIDS"],"offsets":[[221,225]],"normalized":[{"db_name":"MESH","db_id":"D000163"}]},{"id":"11382","type":"Disease","text":["infection"],"offsets":[[227,236]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"11383","type":"Disease","text":["leukaemia"],"offsets":[[279,288]],"normalized":[{"db_name":"MESH","db_id":"D007938"}]},{"id":"11384","type":"Chemical","text":["AZT"],"offsets":[[319,322]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"11385","type":"Disease","text":["anaemia"],"offsets":[[331,338]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"11386","type":"Chemical","text":["AZT"],"offsets":[[504,507]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"11387","type":"Chemical","text":["AZT"],"offsets":[[554,557]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"11388","type":"Disease","text":["anaemia"],"offsets":[[567,574]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"11389","type":"Disease","text":["anaemia"],"offsets":[[632,639]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"11390","type":"Chemical","text":["AZT"],"offsets":[[688,691]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"11391","type":"Chemical","text":["AZT"],"offsets":[[920,923]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"11392","type":"Chemical","text":["AZT"],"offsets":[[1158,1161]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"11393","type":"Disease","text":["anaemia"],"offsets":[[1210,1217]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"11394","type":"Chemical","text":["phenylhydrazine"],"offsets":[[1246,1261]],"normalized":[{"db_name":"MESH","db_id":"C030299"}]},{"id":"11395","type":"Chemical","text":["PHZ"],"offsets":[[1263,1266]],"normalized":[{"db_name":"MESH","db_id":"C030299"}]},{"id":"11396","type":"Chemical","text":["AZT"],"offsets":[[1379,1382]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"11397","type":"Chemical","text":["PHZ"],"offsets":[[1387,1390]],"normalized":[{"db_name":"MESH","db_id":"C030299"}]},{"id":"11398","type":"Disease","text":["anaemia"],"offsets":[[1428,1435]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"11399","type":"Disease","text":["reticulocytosis"],"offsets":[[1446,1461]],"normalized":[{"db_name":"MESH","db_id":"D045262"}]},{"id":"11400","type":"Disease","text":["anaemia"],"offsets":[[1498,1505]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"11401","type":"Chemical","text":["AZT"],"offsets":[[1518,1521]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"11402","type":"Chemical","text":["AZT"],"offsets":[[1545,1548]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"11403","type":"Disease","text":["anaemia"],"offsets":[[1568,1575]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]}],"events":[],"coreferences":[],"relations":[{"id":"11404","type":"CID","arg1_id":"11376","arg2_id":"11378","normalized":[]},{"id":"11405","type":"CID","arg1_id":"11376","arg2_id":"11385","normalized":[]},{"id":"11406","type":"CID","arg1_id":"11376","arg2_id":"11388","normalized":[]},{"id":"11407","type":"CID","arg1_id":"11376","arg2_id":"11389","normalized":[]},{"id":"11408","type":"CID","arg1_id":"11376","arg2_id":"11393","normalized":[]},{"id":"11409","type":"CID","arg1_id":"11376","arg2_id":"11398","normalized":[]},{"id":"11410","type":"CID","arg1_id":"11376","arg2_id":"11400","normalized":[]},{"id":"11411","type":"CID","arg1_id":"11376","arg2_id":"11403","normalized":[]},{"id":"11412","type":"CID","arg1_id":"11379","arg2_id":"11378","normalized":[]},{"id":"11413","type":"CID","arg1_id":"11379","arg2_id":"11385","normalized":[]},{"id":"11414","type":"CID","arg1_id":"11379","arg2_id":"11388","normalized":[]},{"id":"11415","type":"CID","arg1_id":"11379","arg2_id":"11389","normalized":[]},{"id":"11416","type":"CID","arg1_id":"11379","arg2_id":"11393","normalized":[]},{"id":"11417","type":"CID","arg1_id":"11379","arg2_id":"11398","normalized":[]},{"id":"11418","type":"CID","arg1_id":"11379","arg2_id":"11400","normalized":[]},{"id":"11419","type":"CID","arg1_id":"11379","arg2_id":"11403","normalized":[]},{"id":"11420","type":"CID","arg1_id":"11380","arg2_id":"11378","normalized":[]},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{"id":"11500","document_id":"1732442","passages":[{"id":"11501","type":"title","text":["Detection of abnormal cardiac adrenergic neuron activity in adriamycin-induced cardiomyopathy with iodine-125-metaiodobenzylguanidine."],"offsets":[[0,134]]},{"id":"11502","type":"abstract","text":["Radiolabeled metaiodobenzylguanidine (MIBG), an analog of norepinephrine (NE), serves as an index of adrenergic neuron integrity and function. Using a rat model of adriamycin-induced cardiomyopathy, we tested the hypothesis that abnormal cardiac adrenergic neuron activity may appear and be exacerbated dose-dependently in adriamycin cardiomyopathy. The degree of vacuolar degeneration of myocardial cells was analyzed in relation to the duration of adriamycin treatment (2 mg\/kg, once a week). There were no abnormalities or only isolated degeneration in the 1- or 2-wk treatment groups, isolated or scattered degeneration in half of the 3-wk group, frequent scattered degeneration in the 4-wk group, scattered or focal degeneration in the 5-wk group, and extensive degeneration in the 8-wk group. Myocardial accumulation of [125I]MIBG 4 hr after intravenous injection did not differ between the controls and the groups treated 3 wk or less. However, the 4-wk group had a slightly lower accumulation in the right ventricular wall (82% of the control) and significantly lower accumulation in the left ventricular wall (about 66% of the control: p less than 0.05). In the 5-wk group, MIBG accumulation in the right and left ventricular wall was 35% and 27% of that in controls, respectively (p less than 0.001). In the 8-wk group, MIBG accumulation in the right and left ventricular wall was 18% and 14% of that in controls, respectively (p less than 0.001). Thus, MIBG accumulation in the myocardium decreased in an adriamycin dose-dependent manner. The appearance of impaired cardiac adrenergic neuron activity in the presence of slight myocardial impairment (scattered or focal vacuolar degeneration) indicates that MIBG scintigraphy may be a useful method for detection of adriamycin-induced cardiomyopathy."],"offsets":[[135,1945]]}],"entities":[{"id":"11503","type":"Chemical","text":["adriamycin"],"offsets":[[60,70]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"11504","type":"Disease","text":["cardiomyopathy"],"offsets":[[79,93]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"11505","type":"Chemical","text":["iodine-125-metaiodobenzylguanidine"],"offsets":[[99,133]],"normalized":[{"db_name":"MESH","db_id":"D019797"}]},{"id":"11506","type":"Chemical","text":["Radiolabeled 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{"id":"11556","document_id":"1423339","passages":[{"id":"11557","type":"title","text":["Amnestic syndrome associated with propranolol toxicity: a case report."],"offsets":[[0,70]]},{"id":"11558","type":"abstract","text":["An elderly woman developed an Alzheimer-like subacute dementia as a result of propranolol toxicity. Analysis of the manifestations showed that severe impairment of memory accounted for virtually all of the abnormalities. There is evidence that cerebral reactions to drug toxicity can exhibit patterns that suggest highly selective involvement of functional subdivisions of the brain."],"offsets":[[71,454]]}],"entities":[{"id":"11559","type":"Disease","text":["Amnestic syndrome"],"offsets":[[0,17]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"11560","type":"Chemical","text":["propranolol"],"offsets":[[34,45]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"11561","type":"Disease","text":["toxicity"],"offsets":[[46,54]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"11562","type":"Disease","text":["Alzheimer"],"offsets":[[101,110]],"normalized":[{"db_name":"MESH","db_id":"D000544"}]},{"id":"11563","type":"Disease","text":["dementia"],"offsets":[[125,133]],"normalized":[{"db_name":"MESH","db_id":"D003704"}]},{"id":"11564","type":"Chemical","text":["propranolol"],"offsets":[[149,160]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"11565","type":"Disease","text":["toxicity"],"offsets":[[161,169]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"11566","type":"Disease","text":["toxicity"],"offsets":[[342,350]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]}],"events":[],"coreferences":[],"relations":[{"id":"11567","type":"CID","arg1_id":"11560","arg2_id":"11559","normalized":[]},{"id":"11568","type":"CID","arg1_id":"11564","arg2_id":"11559","normalized":[]}]}
{"id":"11569","document_id":"921394","passages":[{"id":"11570","type":"title","text":["Biphasic response of the SA node of the dog heart in vivo to selective administration of ketamine."],"offsets":[[0,98]]},{"id":"11571","type":"abstract","text":["Effect of ketamine on the SA node of the dog heart was studied in vivo using a selective perfusion technique of the SA node artery. Injections of ketamine in doses from 100 microgram to 3 mg into the artery produced a depression of the SA nodal activity by a direct action. This depression was followed by the sudden appearance of a stimulatory phase. Bilateral vagotomy and sympathectomy or prior administration of a ganglion blocker failed to inhibit the occurrence of the ketamine-induced tachycardia, while it was completely abolished in the reserpinized dogs or by a prior injection of a beta-blocking agent into the SA node artery. This may indicate that an activation of the peripheral adrenergic mechanism plays an important role in the induction of the excitatory effect of ketamine injected in the SA node artery."],"offsets":[[99,922]]}],"entities":[{"id":"11572","type":"Chemical","text":["ketamine"],"offsets":[[89,97]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"11573","type":"Chemical","text":["ketamine"],"offsets":[[109,117]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"11574","type":"Chemical","text":["ketamine"],"offsets":[[245,253]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"11575","type":"Disease","text":["depression"],"offsets":[[317,327]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"11576","type":"Disease","text":["depression"],"offsets":[[378,388]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"11577","type":"Chemical","text":["ketamine"],"offsets":[[574,582]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"11578","type":"Disease","text":["tachycardia"],"offsets":[[591,602]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]},{"id":"11579","type":"Chemical","text":["ketamine"],"offsets":[[882,890]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]}],"events":[],"coreferences":[],"relations":[{"id":"11580","type":"CID","arg1_id":"11572","arg2_id":"11578","normalized":[]},{"id":"11581","type":"CID","arg1_id":"11573","arg2_id":"11578","normalized":[]},{"id":"11582","type":"CID","arg1_id":"11574","arg2_id":"11578","normalized":[]},{"id":"11583","type":"CID","arg1_id":"11577","arg2_id":"11578","normalized":[]},{"id":"11584","type":"CID","arg1_id":"11579","arg2_id":"11578","normalized":[]}]}
{"id":"11585","document_id":"871943","passages":[{"id":"11586","type":"title","text":["The use of serum cholinesterase in succinylcholine apnoea."],"offsets":[[0,58]]},{"id":"11587","type":"abstract","text":["Fifteen patients demonstrating unexpected prolonged apnoea lasting several hours after succinylcholine have been treated by a new preparation of human serum cholinesterase. Adequate spontaneous respiration was re-established in an average period of ten minutes after the injection. In 12 patients biochemical genetic examinations confirmed the presence of an atypical serum cholinesterase. In three patients none of the usual variants were found. It is therefore supposed that other unknown variants of serum cholinesterase exist which cannot hydrolyze succinylcholine. The use of serum cholinesterase in succinylcholine apnoea provided considerable relief to both patient and anaesthetist."],"offsets":[[59,749]]}],"entities":[{"id":"11588","type":"Chemical","text":["succinylcholine"],"offsets":[[35,50]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"11589","type":"Disease","text":["apnoea"],"offsets":[[51,57]],"normalized":[{"db_name":"MESH","db_id":"D001049"}]},{"id":"11590","type":"Disease","text":["apnoea"],"offsets":[[111,117]],"normalized":[{"db_name":"MESH","db_id":"D001049"}]},{"id":"11591","type":"Chemical","text":["succinylcholine"],"offsets":[[146,161]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"11592","type":"Chemical","text":["succinylcholine"],"offsets":[[612,627]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"11593","type":"Chemical","text":["succinylcholine"],"offsets":[[664,679]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"11594","type":"Disease","text":["apnoea"],"offsets":[[680,686]],"normalized":[{"db_name":"MESH","db_id":"D001049"}]}],"events":[],"coreferences":[],"relations":[{"id":"11595","type":"CID","arg1_id":"11588","arg2_id":"11589","normalized":[]},{"id":"11596","type":"CID","arg1_id":"11588","arg2_id":"11590","normalized":[]},{"id":"11597","type":"CID","arg1_id":"11588","arg2_id":"11594","normalized":[]},{"id":"11598","type":"CID","arg1_id":"11591","arg2_id":"11589","normalized":[]},{"id":"11599","type":"CID","arg1_id":"11591","arg2_id":"11590","normalized":[]},{"id":"11600","type":"CID","arg1_id":"11591","arg2_id":"11594","normalized":[]},{"id":"11601","type":"CID","arg1_id":"11592","arg2_id":"11589","normalized":[]},{"id":"11602","type":"CID","arg1_id":"11592","arg2_id":"11590","normalized":[]},{"id":"11603","type":"CID","arg1_id":"11592","arg2_id":"11594","normalized":[]},{"id":"11604","type":"CID","arg1_id":"11593","arg2_id":"11589","normalized":[]},{"id":"11605","type":"CID","arg1_id":"11593","arg2_id":"11590","normalized":[]},{"id":"11606","type":"CID","arg1_id":"11593","arg2_id":"11594","normalized":[]}]}
{"id":"11607","document_id":"1355091","passages":[{"id":"11608","type":"title","text":["Orthostatic hypotension occurs following alpha 2-adrenoceptor blockade in chronic prazosin-pretreated conscious spontaneously hypertensive rats."],"offsets":[[0,144]]},{"id":"11609","type":"abstract","text":["1. Studies were performed to evaluate whether chronic prazosin treatment alters the alpha 2-adrenoceptor function for orthostatic control of arterial blood pressure in conscious spontaneously hypertensive rats (SHR). 2. Conscious SHR (male 300-350 g) were subjected to 90 degrees head-up tilts for 60 s following acute administration of prazosin (0.1 mg kg-1 i.p.) or rauwolscine (3 mg kg-1 i.v.). Orthostatic hypotension was determined by the average decrease (%) in mean arterial pressure (MAP femoral) over the 60-s tilt period. The basal MAP of conscious SHR was reduced to a similar extent by prazosin (-23%(-)-26% MAP) and rauwolscine (-16%(-)-33% MAP). However, the head-up tilt induced orthostatic hypotension in the SHR treated with prazosin (-16% MAP, n = 6), but not in the SHR treated with rauwolscine (less than +2% MAP, n = 6). 3. Conscious SHR were treated for 4 days with prazosin at 2 mg kg-1 day-1 i.p. for chronic alpha 1-adrenoceptor blockade. MAP in conscious SHR after chronic prazosin treatment was 14% lower than in the untreated SHR (n = 8). Head-up tilts in these rats did not produce orthostatic hypotension when performed either prior to or after acute dosing of prazosin (0.1 mg kg-1 i.p.). Conversely, administration of rauwolscine (3 mg kg-1 i.v.) in chronic prazosin treated SHR decreased the basal MAP by 12-31% (n = 4), and subsequent tilts induced further drops of MAP by 19-23% in these rats. 4. The pressor responses and bradycardia to the alpha 1-agonist cirazoline (0.6 and 2 micrograms kg-1 i.v.), the alpha 2-agonist Abbott-53693 (1 and 3 micrograms kg-1 i.v.), and noradrenaline (0.1 and 1.0 micrograms kg-1 i.v.) were determined in conscious SHR with and without chronic prazosin pretreatment. Both the pressor and bradycardia effects of cirazoline were abolished in chronic prazosin treated SHR (n = 4) as compared to the untreated SHR (n = 4). On the other hand, the pressor effects of Abbott-53693 were similar in both groups of SHR, but the accompanying bradycardia was greater in SHR with chronic prazosin treatment than without such treatment. Furthermore, the bradycardia that accompanied the noradrenaline-induced pressor effect in SHR was similar with and without chronic prazosin treatment despite a 47-71% reduction of the pressor effect in chronic alpha 1-receptor blocked SHR.(ABSTRACT TRUNCATED AT 400 WORDS)"],"offsets":[[145,2510]]}],"entities":[{"id":"11610","type":"Disease","text":["Orthostatic hypotension"],"offsets":[[0,23]],"normalized":[{"db_name":"MESH","db_id":"D007024"}]},{"id":"11611","type":"Chemical","text":["prazosin"],"offsets":[[82,90]],"normalized":[{"db_name":"MESH","db_id":"D011224"}]},{"id":"11612","type":"Disease","text":["hypertensive"],"offsets":[[126,138]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"11613","type":"Chemical","text":["prazosin"],"offsets":[[199,207]],"normalized":[{"db_name":"MESH","db_id":"D011224"}]},{"id":"11614","type":"Disease","text":["hypertensive"],"offsets":[[337,349]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"11615","type":"Chemical","text":["prazosin"],"offsets":[[482,490]],"normalized":[{"db_name":"MESH","db_id":"D011224"}]},{"id":"11616","type":"Chemical","text":["rauwolscine"],"offsets":[[513,524]],"normalized":[{"db_name":"MESH","db_id":"D015016"}]},{"id":"11617","type":"Disease","text":["Orthostatic 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In this case, the authors postulate that the use of estradiol and progesterone and the underlying DM increased vascular thrombogenicity, which provided a common denominator for thrombosis of both the ICA and the venous sinus."],"offsets":[[131,1013]]}],"entities":[{"id":"11734","type":"Disease","text":["cerebral venous sinus and internal carotid artery thrombosis"],"offsets":[[15,75]],"normalized":[{"db_name":"MESH","db_id":"D012851"},{"db_name":"MESH","db_id":"D002341"}]},{"id":"11735","type":"Disease","text":["cerebral venous sinus","thrombosis"],"offsets":[[15,36],[65,75]],"normalized":[{"db_name":"MESH","db_id":"D012851"}]},{"id":"11736","type":"Disease","text":["internal carotid artery 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{"id":"11820","document_id":"1628552","passages":[{"id":"11821","type":"title","text":["Chloroquine related complete heart block with blindness: case report."],"offsets":[[0,69]]},{"id":"11822","type":"abstract","text":["A 27-year old African woman with history of regular chloroquine ingestion presented with progressive deterioration of vision, easy fatiguability, dyspnoea, dizziness progressing to syncopal attacks. Ophthalmological assessment revealed features of chloroquine retinopathy, cardiac assessment revealed features of heart failure and a complete heart block with right bundle branch block pattern. The heart block was treated by pacemaker insertion and the heart failure resolved spontaneously following chloroquine discontinuation. She however remains blind."],"offsets":[[70,625]]}],"entities":[{"id":"11823","type":"Chemical","text":["Chloroquine"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D002738"}]},{"id":"11824","type":"Disease","text":["heart block"],"offsets":[[29,40]],"normalized":[{"db_name":"MESH","db_id":"D006327"}]},{"id":"11825","type":"Disease","text":["blindness"],"offsets":[[46,55]],"normalized":[{"db_name":"MESH","db_id":"D001766"}]},{"id":"11826","type":"Chemical","text":["chloroquine"],"offsets":[[122,133]],"normalized":[{"db_name":"MESH","db_id":"D002738"}]},{"id":"11827","type":"Disease","text":["deterioration of vision"],"offsets":[[171,194]],"normalized":[{"db_name":"MESH","db_id":"D015354"}]},{"id":"11828","type":"Disease","text":["fatiguability"],"offsets":[[201,214]],"normalized":[{"db_name":"MESH","db_id":"D005221"}]},{"id":"11829","type":"Disease","text":["dyspnoea"],"offsets":[[216,224]],"normalized":[{"db_name":"MESH","db_id":"D004417"}]},{"id":"11830","type":"Disease","text":["dizziness"],"offsets":[[226,235]],"normalized":[{"db_name":"MESH","db_id":"D004244"}]},{"id":"11831","type":"Disease","text":["syncopal attacks"],"offsets":[[251,267]],"normalized":[{"db_name":"MESH","db_id":"D013575"}]},{"id":"11832","type":"Chemical","text":["chloroquine"],"offsets":[[318,329]],"normalized":[{"db_name":"MESH","db_id":"D002738"}]},{"id":"11833","type":"Disease","text":["retinopathy"],"offsets":[[330,341]],"normalized":[{"db_name":"MESH","db_id":"D012164"}]},{"id":"11834","type":"Disease","text":["heart failure"],"offsets":[[383,396]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"11835","type":"Disease","text":["heart block"],"offsets":[[412,423]],"normalized":[{"db_name":"MESH","db_id":"D006327"}]},{"id":"11836","type":"Disease","text":["right bundle branch block"],"offsets":[[429,454]],"normalized":[{"db_name":"MESH","db_id":"D002037"}]},{"id":"11837","type":"Disease","text":["heart block"],"offsets":[[468,479]],"normalized":[{"db_name":"MESH","db_id":"D006327"}]},{"id":"11838","type":"Disease","text":["heart failure"],"offsets":[[523,536]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"11839","type":"Chemical","text":["chloroquine"],"offsets":[[570,581]],"normalized":[{"db_name":"MESH","db_id":"D002738"}]},{"id":"11840","type":"Disease","text":["blind"],"offsets":[[619,624]],"normalized":[{"db_name":"MESH","db_id":"D001766"}]}],"events":[],"coreferences":[],"relations":[{"id":"11841","type":"CID","arg1_id":"11823","arg2_id":"11828","normalized":[]},{"id":"11842","type":"CID","arg1_id":"11826","arg2_id":"11828","normalized":[]},{"id":"11843","type":"CID","arg1_id":"11832","arg2_id":"11828","normalized":[]},{"id":"11844","type":"CID","arg1_id":"11839","arg2_id":"11828","normalized":[]},{"id":"11845","type":"CID","arg1_id":"11823","arg2_id":"11834","normalized":[]},{"id":"11846","type":"CID","arg1_id":"11823","arg2_id":"11838","normalized":[]},{"id":"11847","type":"CID","arg1_id":"11826","arg2_id":"11834","normalized":[]},{"id":"11848","type":"CID","arg1_id":"11826","arg2_id":"11838","normalized":[]},{"id":"11849","type":"CID","arg1_id":"11832","arg2_id":"11834","normalized":[]},{"id":"11850","type":"CID","arg1_id":"11832","arg2_id":"11838","normalized":[]},{"id":"11851","type":"CID","arg1_id":"11839","arg2_id":"11834","normalized":[]},{"id":"11852","type":"CID","arg1_id":"11839","arg2_id":"11838","normalized":[]},{"id":"11853","type":"CID","arg1_id":"11823","arg2_id":"11829","normalized":[]},{"id":"11854","type":"CID","arg1_id":"11826","arg2_id":"11829","normalized":[]},{"id":"11855","type":"CID","arg1_id":"11832","arg2_id":"11829","normalized":[]},{"id":"11856","type":"CID","arg1_id":"11839","arg2_id":"11829","normalized":[]},{"id":"11857","type":"CID","arg1_id":"11823","arg2_id":"11831","normalized":[]},{"id":"11858","type":"CID","arg1_id":"11826","arg2_id":"11831","normalized":[]},{"id":"11859","type":"CID","arg1_id":"11832","arg2_id":"11831","normalized":[]},{"id":"11860","type":"CID","arg1_id":"11839","arg2_id":"11831","normalized":[]},{"id":"11861","type":"CID","arg1_id":"11823","arg2_id":"11836","normalized":[]},{"id":"11862","type":"CID","arg1_id":"11826","arg2_id":"11836","normalized":[]},{"id":"11863","type":"CID","arg1_id":"11832","arg2_id":"11836","normalized":[]},{"id":"11864","type":"CID","arg1_id":"11839","arg2_id":"11836","normalized":[]},{"id":"11865","type":"CID","arg1_id":"11823","arg2_id":"11825","normalized":[]},{"id":"11866","type":"CID","arg1_id":"11823","arg2_id":"11840","normalized":[]},{"id":"11867","type":"CID","arg1_id":"11826","arg2_id":"11825","normalized":[]},{"id":"11868","type":"CID","arg1_id":"11826","arg2_id":"11840","normalized":[]},{"id":"11869","type":"CID","arg1_id":"11832","arg2_id":"11825","normalized":[]},{"id":"11870","type":"CID","arg1_id":"11832","arg2_id":"11840","normalized":[]},{"id":"11871","type":"CID","arg1_id":"11839","arg2_id":"11825","normalized":[]},{"id":"11872","type":"CID","arg1_id":"11839","arg2_id":"11840","normalized":[]},{"id":"11873","type":"CID","arg1_id":"11823","arg2_id":"11833","normalized":[]},{"id":"11874","type":"CID","arg1_id":"11826","arg2_id":"11833","normalized":[]},{"id":"11875","type":"CID","arg1_id":"11832","arg2_id":"11833","normalized":[]},{"id":"11876","type":"CID","arg1_id":"11839","arg2_id":"11833","normalized":[]},{"id":"11877","type":"CID","arg1_id":"11823","arg2_id":"11830","normalized":[]},{"id":"11878","type":"CID","arg1_id":"11826","arg2_id":"11830","normalized":[]},{"id":"11879","type":"CID","arg1_id":"11832","arg2_id":"11830","normalized":[]},{"id":"11880","type":"CID","arg1_id":"11839","arg2_id":"11830","normalized":[]}]}
{"id":"11881","document_id":"11524350","passages":[{"id":"11882","type":"title","text":["Systemic toxicity and resuscitation in bupivacaine-, levobupivacaine-, or ropivacaine-infused rats."],"offsets":[[0,99]]},{"id":"11883","type":"abstract","text":["We compared the systemic toxicity of bupivacaine, levobupivacaine, and ropivacaine in anesthetized rats. We also compared the ability to resuscitate rats after lethal doses of these local anesthetics. Bupivacaine, levobupivacaine, or ropivacaine was infused at a rate of 2 mg. kg(-1). min(-1) while electrocardiogram, electroencephalogram, and arterial pressure were continuously monitored. When asystole was recorded, drug infusion was stopped and a resuscitation sequence was begun. Epinephrine 0.01 mg\/kg was administered at 1-min intervals while external cardiac compressions were applied. Resuscitation was considered successful when a systolic arterial pressure > or =100 mm Hg was achieved within 5 min. The cumulative doses of levobupivacaine and ropivacaine that produced seizures were similar and were larger than those of bupivacaine. The cumulative doses of levobupivacaine that produced dysrhythmias and asystole were smaller than the corresponding doses of ropivacaine, but they were larger than those of bupivacaine. The number of successful resuscitations did not differ among groups. However, a smaller dose of epinephrine was required in the Ropivacaine group than in the other groups. We conclude that the systemic toxicity of levobupivacaine is intermediate between that of ropivacaine and bupivacaine when administered at the same rate and that ropivacaine-induced cardiac arrest appears to be more susceptible to treatment than that induced by bupivacaine or levobupivacaine."],"offsets":[[100,1597]]}],"entities":[{"id":"11884","type":"Disease","text":["toxicity"],"offsets":[[9,17]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"11885","type":"Chemical","text":["bupivacaine"],"offsets":[[39,50]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"11886","type":"Chemical","text":["levobupivacaine"],"offsets":[[53,68]],"normalized":[{"db_name":"MESH","db_id":"C476513"}]},{"id":"11887","type":"Chemical","text":["ropivacaine"],"offsets":[[74,85]],"normalized":[{"db_name":"MESH","db_id":"C037663"}]},{"id":"11888","type":"Disease","text":["toxicity"],"offsets":[[125,133]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"11889","type":"Chemical","text":["bupivacaine"],"offsets":[[137,148]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"11890","type":"Chemical","text":["levobupivacaine"],"offsets":[[150,165]],"normalized":[{"db_name":"MESH","db_id":"C476513"}]},{"id":"11891","type":"Chemical","text":["ropivacaine"],"offsets":[[171,182]],"normalized":[{"db_name":"MESH","db_id":"C037663"}]},{"id":"11892","type":"Chemical","text":["Bupivacaine"],"offsets":[[301,312]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"11893","type":"Chemical","text":["levobupivacaine"],"offsets":[[314,329]],"normalized":[{"db_name":"MESH","db_id":"C476513"}]},{"id":"11894","type":"Chemical","text":["ropivacaine"],"offsets":[[334,345]],"normalized":[{"db_name":"MESH","db_id":"C037663"}]},{"id":"11895","type":"Disease","text":["asystole"],"offsets":[[496,504]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"11896","type":"Chemical","text":["Epinephrine"],"offsets":[[585,596]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"11897","type":"Chemical","text":["levobupivacaine"],"offsets":[[835,850]],"normalized":[{"db_name":"MESH","db_id":"C476513"}]},{"id":"11898","type":"Chemical","text":["ropivacaine"],"offsets":[[855,866]],"normalized":[{"db_name":"MESH","db_id":"C037663"}]},{"id":"11899","type":"Disease","text":["seizures"],"offsets":[[881,889]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"11900","type":"Chemical","text":["bupivacaine"],"offsets":[[933,944]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"11901","type":"Chemical","text":["levobupivacaine"],"offsets":[[970,985]],"normalized":[{"db_name":"MESH","db_id":"C476513"}]},{"id":"11902","type":"Disease","text":["dysrhythmias"],"offsets":[[1000,1012]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"11903","type":"Disease","text":["asystole"],"offsets":[[1017,1025]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"11904","type":"Chemical","text":["ropivacaine"],"offsets":[[1071,1082]],"normalized":[{"db_name":"MESH","db_id":"C037663"}]},{"id":"11905","type":"Chemical","text":["bupivacaine"],"offsets":[[1119,1130]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"11906","type":"Chemical","text":["epinephrine"],"offsets":[[1228,1239]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"11907","type":"Chemical","text":["Ropivacaine"],"offsets":[[1260,1271]],"normalized":[{"db_name":"MESH","db_id":"C037663"}]},{"id":"11908","type":"Disease","text":["toxicity"],"offsets":[[1334,1342]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"11909","type":"Chemical","text":["levobupivacaine"],"offsets":[[1346,1361]],"normalized":[{"db_name":"MESH","db_id":"C476513"}]},{"id":"11910","type":"Chemical","text":["ropivacaine"],"offsets":[[1394,1405]],"normalized":[{"db_name":"MESH","db_id":"C037663"}]},{"id":"11911","type":"Chemical","text":["bupivacaine"],"offsets":[[1410,1421]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"11912","type":"Chemical","text":["ropivacaine"],"offsets":[[1466,1477]],"normalized":[{"db_name":"MESH","db_id":"C037663"}]},{"id":"11913","type":"Disease","text":["cardiac arrest"],"offsets":[[1486,1500]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"11914","type":"Chemical","text":["bupivacaine"],"offsets":[[1566,1577]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"11915","type":"Chemical","text":["levobupivacaine"],"offsets":[[1581,1596]],"normalized":[{"db_name":"MESH","db_id":"C476513"}]}],"events":[],"coreferences":[],"relations":[{"id":"11916","type":"CID","arg1_id":"11886","arg2_id":"11902","normalized":[]},{"id":"11917","type":"CID","arg1_id":"11890","arg2_id":"11902","normalized":[]},{"id":"11918","type":"CID","arg1_id":"11893","arg2_id":"11902","normalized":[]},{"id":"11919","type":"CID","arg1_id":"11897","arg2_id":"11902","normalized":[]},{"id":"11920","type":"CID","arg1_id":"11901","arg2_id":"11902","normalized":[]},{"id":"11921","type":"CID","arg1_id":"11909","arg2_id":"11902","normalized":[]},{"id":"11922","type":"CID","arg1_id":"11915","arg2_id":"11902","normalized":[]},{"id":"11923","type":"CID","arg1_id":"11887","arg2_id":"11899","normalized":[]},{"id":"11924","type":"CID","arg1_id":"11891","arg2_id":"11899","normalized":[]},{"id":"11925","type":"CID","arg1_id":"11894","arg2_id":"11899","normalized":[]},{"id":"11926","type":"CID","arg1_id":"11898","arg2_id":"11899","normalized":[]},{"id":"11927","type":"CID","arg1_id":"11904","arg2_id":"11899","normalized":[]},{"id":"11928","type":"CID","arg1_id":"11907","arg2_id":"11899","normalized":[]},{"id":"11929","type":"CID","arg1_id":"11910","arg2_id":"11899","normalized":[]},{"id":"11930","type":"CID","arg1_id":"11912","arg2_id":"11899","normalized":[]},{"id":"11931","type":"CID","arg1_id":"11887","arg2_id":"11895","normalized":[]},{"id":"11932","type":"CID","arg1_id":"11887","arg2_id":"11903","normalized":[]},{"id":"11933","type":"CID","arg1_id":"11887","arg2_id":"11913","normalized":[]},{"id":"11934","type":"CID","arg1_id":"11891","arg2_id":"11895","normalized":[]},{"id":"11935","type":"CID","arg1_id":"11891","arg2_id":"11903","normalized":[]},{"id":"11936","type":"CID","arg1_id":"11891","arg2_id":"11913","normalized":[]},{"id":"11937","type":"CID","arg1_id":"11894","arg2_id":"11895","normalized":[]},{"id":"11938","type":"CID","arg1_id":"11894","arg2_id":"11903","normalized":[]},{"id":"11939","type":"CID","arg1_id":"11894","arg2_id":"11913","normalized":[]},{"id":"11940","type":"CID","arg1_id":"11898","arg2_id":"11895","normalized":[]},{"id":"11941","type":"CID","arg1_id":"11898","arg2_id":"11903","normalized":[]},{"id":"11942","type":"CID","arg1_id":"11898","arg2_id":"11913","normalized":[]},{"id":"11943","type":"CID","arg1_id":"11904","arg2_id":"11895","normalized":[]},{"id":"11944","type":"CID","arg1_id":"11904","arg2_id":"11903","normalized":[]},{"id":"11945","type":"CID","arg1_id":"11904","arg2_id":"11913","normalized":[]},{"id":"11946","type":"CID","arg1_id":"11907","arg2_id":"11895","normalized":[]},{"id":"11947","type":"CID","arg1_id":"11907","arg2_id":"11903","normalized":[]},{"id":"11948","type":"CID","arg1_id":"11907","arg2_id":"11913","normalized":[]},{"id":"11949","type":"CID","arg1_id":"11910","arg2_id":"11895","normalized":[]},{"id":"11950","type":"CID","arg1_id":"11910","arg2_id":"11903","normalized":[]},{"id":"11951","type":"CID","arg1_id":"11910","arg2_id":"11913","normalized":[]},{"id":"11952","type":"CID","arg1_id":"11912","arg2_id":"11895","normalized":[]},{"id":"11953","type":"CID","arg1_id":"11912","arg2_id":"11903","normalized":[]},{"id":"11954","type":"CID","arg1_id":"11912","arg2_id":"11913","normalized":[]},{"id":"11955","type":"CID","arg1_id":"11886","arg2_id":"11899","normalized":[]},{"id":"11956","type":"CID","arg1_id":"11890","arg2_id":"11899","normalized":[]},{"id":"11957","type":"CID","arg1_id":"11893","arg2_id":"11899","normalized":[]},{"id":"11958","type":"CID","arg1_id":"11897","arg2_id":"11899","normalized":[]},{"id":"11959","type":"CID","arg1_id":"11901","arg2_id":"11899","normalized":[]},{"id":"11960","type":"CID","arg1_id":"11909","arg2_id":"11899","normalized":[]},{"id":"11961","type":"CID","arg1_id":"11915","arg2_id":"11899","normalized":[]},{"id":"11962","type":"CID","arg1_id":"11887","arg2_id":"11902","normalized":[]},{"id":"11963","type":"CID","arg1_id":"11891","arg2_id":"11902","normalized":[]},{"id":"11964","type":"CID","arg1_id":"11894","arg2_id":"11902","normalized":[]},{"id":"11965","type":"CID","arg1_id":"11898","arg2_id":"11902","normalized":[]},{"id":"11966","type":"CID","arg1_id":"11904","arg2_id":"11902","normalized":[]},{"id":"11967","type":"CID","arg1_id":"11907","arg2_id":"11902","normalized":[]},{"id":"11968","type":"CID","arg1_id":"11910","arg2_id":"11902","normalized":[]},{"id":"11969","type":"CID","arg1_id":"11912","arg2_id":"11902","normalized":[]},{"id":"11970","type":"CID","arg1_id":"11886","arg2_id":"11895","normalized":[]},{"id":"11971","type":"CID","arg1_id":"11886","arg2_id":"11903","normalized":[]},{"id":"11972","type":"CID","arg1_id":"11886","arg2_id":"11913","normalized":[]},{"id":"11973","type":"CID","arg1_id":"1189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{"id":"11991","document_id":"10027919","passages":[{"id":"11992","type":"title","text":["22-oxacalcitriol suppresses secondary hyperparathyroidism without inducing low bone turnover in dogs with renal failure."],"offsets":[[0,120]]},{"id":"11993","type":"abstract","text":["BACKGROUND: Calcitriol therapy suppresses serum levels of parathyroid hormone (PTH) in patients with renal failure but has several drawbacks, including hypercalcemia and\/or marked suppression of bone turnover, which may lead to adynamic bone disease. A new vitamin D analogue, 22-oxacalcitriol (OCT), has been shown to have promising characteristics. This study was undertaken to determine the effects of OCT on serum PTH levels and bone turnover in states of normal or impaired renal function. METHODS: Sixty dogs were either nephrectomized (Nx, N = 38) or sham-operated (Sham, N = 22). The animals received supplemental phosphate to enhance PTH secretion. Fourteen weeks after the start of phosphate supplementation, half of the Nx and Sham dogs received doses of OCT (three times per week); the other half were given vehicle for 60 weeks. Thereafter, the treatment modalities for a subset of animals were crossed over for an additional eight months. Biochemical and hormonal indices of calcium and bone metabolism were measured throughout the study, and bone biopsies were done at baseline, 60 weeks after OCT or vehicle treatment, and at the end of the crossover period. RESULTS: In Nx dogs, OCT significantly decreased serum PTH levels soon after the induction of renal insufficiency. In long-standing secondary hyperparathyroidism, OCT (0.03 microg\/kg) stabilized serum PTH levels during the first months. Serum PTH levels rose thereafter, but the rise was less pronounced compared with baseline than the rise seen in Nx control. These effects were accompanied by episodes of hypercalcemia and hyperphosphatemia. In animals with normal renal function, OCT induced a transient decrease in serum PTH levels at a dose of 0.1 microg\/kg, which was not sustained with lowering of the doses. In Nx dogs, OCT reversed abnormal bone formation, such as woven osteoid and fibrosis, but did not significantly alter the level of bone turnover. In addition, OCT improved mineralization lag time, (that is, the rate at which osteoid mineralizes) in both Nx and Sham dogs. CONCLUSIONS: These results indicate that even though OCT does not completely prevent the occurrence of hypercalcemia in experimental dogs with renal insufficiency, it may be of use in the management of secondary hyperparathyroidism because it does not induce low bone turnover and, therefore, does not increase the risk of adynamic bone disease."],"offsets":[[121,2529]]}],"entities":[{"id":"11994","type":"Chemical","text":["22-oxacalcitriol"],"offsets":[[0,16]],"normalized":[{"db_name":"MESH","db_id":"C051883"}]},{"id":"11995","type":"Disease","text":["secondary hyperparathyroidism"],"offsets":[[28,57]],"normalized":[{"db_name":"MESH","db_id":"D006962"}]},{"id":"11996","type":"Disease","text":["low bone turnover"],"offsets":[[75,92]],"normalized":[{"db_name":"MESH","db_id":"D001851"}]},{"id":"11997","type":"Disease","text":["renal failure"],"offsets":[[106,119]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"11998","type":"Chemical","text":["Calcitriol"],"offsets":[[133,143]],"normalized":[{"db_name":"MESH","db_id":"D002117"}]},{"id":"11999","type":"Disease","text":["renal failure"],"offsets":[[222,235]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"12000","type":"Disease","text":["hypercalcemia"],"offsets":[[273,286]],"normalized":[{"db_name":"MESH","db_id":"D006934"}]},{"id":"12001","type":"Disease","text":["suppression of bone turnover"],"offsets":[[301,329]],"normalized":[{"db_name":"MESH","db_id":"D001851"}]},{"id":"12002","type":"Disease","text":["adynamic bone disease"],"offsets":[[349,370]],"normalized":[{"db_name":"MESH","db_id":"D001851"}]},{"id":"12003","type":"Chemical","text":["vitamin D"],"offsets":[[378,387]],"normalized":[{"db_name":"MESH","db_id":"D014807"}]},{"id":"12004","type":"Chemical","text":["22-oxacalcitriol"],"offsets":[[398,414]],"normalized":[{"db_name":"MESH","db_id":"C051883"}]},{"id":"12005","type":"Chemical","text":["OCT"],"offsets":[[416,419]],"normalized":[{"db_name":"MESH","db_id":"C051883"}]},{"id":"12006","type":"Chemical","text":["OCT"],"offsets":[[526,529]],"normalized":[{"db_name":"MESH","db_id":"C051883"}]},{"id":"12007","type":"Disease","text":["impaired renal 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{"id":"12086","document_id":"8643966","passages":[{"id":"12087","type":"title","text":["Chemotherapy of advanced inoperable non-small cell lung cancer with paclitaxel: a phase II trial."],"offsets":[[0,97]]},{"id":"12088","type":"abstract","text":["Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has demonstrated significant antineoplastic activity against different tumor types, notably ovarian and breast carcinoma. Two phase II trials of 24-hour paclitaxel infusions in chemotherapy-naive patients with stage IIIB or IV non-small cell lung cancer (NSCLC) reported response rates of 21% and 24%. Leukopenia was dose limiting: as many as 62.5% of patients experienced grade 4 leukopenia. We investigated the efficacy and toxicity of a 3-hour paclitaxel infusion in a phase II trial in patients with inoperable stage IIIB or IV NSCLC. The 58 patients treated (41 men and 17 women) had a median age of 59 years (age range, 25 to 75) and a performance status of 0 through 2. Most patients (72.4%) had stage IV NSCLC. Paclitaxel 225 mg\/m2 was infused over 3 hours every 3 weeks with standard prophylactic premedication. Of 50 patients evaluable for response, 12 (24%) had partial remission, 26 (52%) had no change, and 12 had disease progression (24%). Hematologic toxicities were mild: only one patient (2%) developed grade 3 or 4 neutropenia, while 29% had grade 1 or 2. Grade 1 or 2 polyneuropathy affected 56% of patients while only one (2%) experienced severe polyneuropathy. Similarly, grade 1 or 2 myalgia\/arthralgia was observed in 63.2% of patients, but only 14.3% experienced grade 3 or 4. Nausea and vomiting were infrequent, with 14% of patients experiencing grade 1 or 2 and only 2% experiencing grade 3 or 4. Paclitaxel is thus an active single agent in this patient population, with a 3-hour infusion proving comparably effective to a 24-hour infusion and superior in terms of the incidence of hematologic and nonhematologic toxicity. Further phase II studies with paclitaxel combined with other drugs active against NSCLC are indicated, and phase III studies comparing paclitaxel with standard chemotherapy remain to be completed."],"offsets":[[98,2009]]}],"entities":[{"id":"12089","type":"Disease","text":["non-small cell lung cancer"],"offsets":[[36,62]],"normalized":[{"db_name":"MESH","db_id":"D002289"}]},{"id":"12090","type":"Chemical","text":["paclitaxel"],"offsets":[[68,78]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"12091","type":"Chemical","text":["Paclitaxel"],"offsets":[[98,108]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"12092","type":"Chemical","text":["Taxol"],"offsets":[[110,115]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"12093","type":"Disease","text":["tumor"],"offsets":[[233,238]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"12094","type":"Disease","text":["ovarian and breast 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{"id":"12183","document_id":"6695415","passages":[{"id":"12184","type":"title","text":["Cerebral hemorrhage associated with phenylpropanolamine in combination with caffeine."],"offsets":[[0,85]]},{"id":"12185","type":"abstract","text":["Phenylpropanolamine (PPA) is a drug that has been associated with serious side effects including stroke. It is often combined with caffeine in diet preparations and \"look-alike\" pills. In order to determine if PPA\/caffeine can lead to stroke in normotensive and\/or hypertensive rats, we administered the combination in six times the allowed human dose calculated on a per weight basis for the rats two times per day for five days. Subarachnoid and cerebral hemorrhage was noted in 18% of the hypertensive rats. A single PPA\/caffeine administration (same dose) lead to acute hypertension in both the normotensive and hypertensive animals. These results suggest that PPA\/caffeine can lead to cerebral hemorrhage in previously hypertensive animals when administered in greater than the allowed dosage. An acute elevation in blood pressure may be a contributing factor."],"offsets":[[86,951]]}],"entities":[{"id":"12186","type":"Disease","text":["Cerebral 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One or more adverse drug reactions occurred in 51% of patients. Adverse effects forced a reduction in the dose of amiodarone in 41% and discontinuation of amiodarone in 10% of patients. The most common symptomatic adverse reactions were tremor or ataxia (35%), nausea and anorexia (8%), visual halos or blurring (6%), thyroid function abnormalities (6%) and pulmonary interstitial infiltrates (5%). Although large-dose amiodarone is highly effective in the long-term treatment of VT or VF refractory to conventional antiarrhythmic drugs, it causes significant toxicity in approximately 50% of patients. However, when the dose is adjusted based on clinical response or the development of adverse effects, 75% of patients with VT or VF can be successfully managed with amiodarone."],"offsets":[[121,1598]]}],"entities":[{"id":"12345","type":"Disease","text":["toxicity"],"offsets":[[23,31]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"12346","type":"Chemical","text":["amiodarone"],"offsets":[[45,55]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"12347","type":"Disease","text":["ventricular tachycardia"],"offsets":[[68,91]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"12348","type":"Disease","text":["ventricular fibrillation"],"offsets":[[95,119]],"normalized":[{"db_name":"MESH","db_id":"D014693"}]},{"id":"12349","type":"Chemical","text":["Amiodarone"],"offsets":[[121,131]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"12350","type":"Disease","text":["ventricular 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{"id":"12415","document_id":"8800187","passages":[{"id":"12416","type":"title","text":["Effect of calcium chloride and 4-aminopyridine therapy on desipramine toxicity in rats."],"offsets":[[0,87]]},{"id":"12417","type":"abstract","text":["BACKGROUND: Hypotension is a major contributor to mortality in tricyclic antidepressant overdose. Recent data suggest that tricyclic antidepressants inhibit calcium influx in some tissues. This study addressed the potential role of calcium channel blockade in tricyclic antidepressant-induced hypotension. METHODS: Two interventions were studied that have been shown previously to improve blood pressure with calcium channel blocker overdose. CaCl2 and 4-aminopyridine. Anesthetized rats received the tricyclic antidepressant desipramine IP to produce hypotension, QRS prolongation, and bradycardia. Fifteen min later, animals received CaCl2, NaHCO3, or saline. In a second experiment, rats received tricyclic antidepressant desipramine IP followed in 15 min by 4-aminopyridine or saline. RESULTS: NaHCO3 briefly (5 min) reversed hypotension and QRS prolongation. CaCl2 and 4-aminopyridine failed to improve blood pressure. The incidence of ventricular arrhythmias (p = 0.004) and seizures (p = 0.03) in the CaCl2 group was higher than the other groups. CONCLUSION: The administration of CaCl2 or 4-aminopyridine did not reverse tricyclic antidepressant-induced hypotension in rats. CaCl2 therapy may possibly worsen both cardiovascular and central nervous system toxicity. These findings do not support a role for calcium channel inhibition in the pathogenesis of tricyclic antidepressant-induced hypotension."],"offsets":[[88,1498]]}],"entities":[{"id":"12418","type":"Chemical","text":["calcium 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{"id":"12485","document_id":"7707116","passages":[{"id":"12486","type":"title","text":["Phase I trial of 13-cis-retinoic acid in children with neuroblastoma following bone marrow transplantation."],"offsets":[[0,107]]},{"id":"12487","type":"abstract","text":["PURPOSE: Treatment of neuroblastoma cell lines with 13-cis-retinoic acid (cis-RA) can cause sustained inhibition of proliferation. Since cis-RA has demonstrated clinical responses in neuroblastoma patients, it may be effective in preventing relapse after cytotoxic therapy. This phase I trial was designed to determine the maximal-tolerated dosage (MTD), toxicities, and pharmacokinetics of cis-RA administered on an intermittent schedule in children with neuroblastoma following bone marrow transplantation (BMT). PATIENTS AND METHODS: Fifty-one assessable patients, 2 to 12 years of age, were treated with oral cis-RA administered in two equally divided doses daily for 2 weeks, followed by a 2-week rest period, for up to 12 courses. The dose was escalated from 100 to 200 mg\/m2\/d until dose-limiting toxicity (DLT) was observed. A single intrapatient dose escalation was permitted. RESULTS: The MTD of cis-RA was 160 mg\/m2\/d. Dose-limiting toxicities in six of nine patients at 200 mg\/m2\/d included hypercalcemia (n = 3), rash (n = 2), and anemia\/thrombocytopenia\/emesis\/rash (n = 1). All toxicities resolved after cis-RA was discontinued. Three complete responses were observed in marrow metastases. Serum levels of 7.4 +\/- 3.0 mumol\/L (peak) and 4.0 +\/- 2.8 mumol\/L (trough) at the MTD were maintained during 14 days of therapy. The DLT correlated with serum levels > or = 10 mumol\/L. CONCLUSION: The MTD of cis-RA given on this intermittent schedule was 160 mg\/m2\/d. Serum levels known to be effective against neuroblastoma in vitro were achieved at this dose. The DLT included hypercalcemia, and may be predicted by serum cis-RA levels. Monitoring of serum calcium and cis-RA levels is indicated in future trials."],"offsets":[[108,1829]]}],"entities":[{"id":"12488","type":"Chemical","text":["13-cis-retinoic acid"],"offsets":[[17,37]],"normalized":[{"db_name":"MESH","db_id":"D015474"}]},{"id":"12489","type":"Disease","text":["neuroblastoma"],"offsets":[[55,68]],"normalized":[{"db_name":"MESH","db_id":"D009447"}]},{"id":"12490","type":"Disease","text":["neuroblastoma"],"offsets":[[130,143]],"normalized":[{"db_name":"MESH","db_id":"D009447"}]},{"id":"12491","type":"Chemical","text":["13-cis-retinoic 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{"id":"12594","document_id":"6892185","passages":[{"id":"12595","type":"title","text":["Effect of calcium chloride on gross behavioural changes produced by carbachol and eserine in cats."],"offsets":[[0,98]]},{"id":"12596","type":"abstract","text":["The effect of calcium chloride injected into the cerebral ventricles of group-housed unanaesthetized cats upon vocalization (rage, hissing and snarling), fighting (attack with paws and claws, defense with paws and claws and biting), mydriasis, tremor and clonic-tonic convulsions produced by carbachol and eserine injected similarly was investigated. Calcium chloride depressed or almost completely abolished the vocalization and fighting due to carbachol and eserine. On the other hand, mydriasis, tremor and clonic-tonic convulsions evoked by carbachol and eserine were not significantly changed by calcium chloride. It is apparent that calcium chloride can \"dissociate\" vocalization and fighting from autonomic and motor phenomena such as mydriasis, tremor and clonic-tonic convulsions caused by carbachol and eserine. Calcium chloride inhibited the vocalization and fighting produced by carbachol and eserine most probably by a nonspecific stabilizing action on central muscarinic cholinoceptive sites. These results further support the view that calcium ions in excess have an atropine-like action also in the central nervous system."],"offsets":[[99,1237]]}],"entities":[{"id":"12597","type":"Chemical","text":["calcium chloride"],"offsets":[[10,26]],"normalized":[{"db_name":"MESH","db_id":"D002122"}]},{"id":"12598","type":"Chemical","text":["carbachol"],"offsets":[[68,77]],"normalized":[{"db_name":"MESH","db_id":"D002217"}]},{"id":"12599","type":"Chemical","text":["eserine"],"offsets":[[82,89]],"normalized":[{"db_name":"MESH","db_id":"D010830"}]},{"id":"12600","type":"Chemical","text":["calcium chloride"],"offsets":[[113,129]],"normalized":[{"db_name":"MESH","db_id":"D002122"}]},{"id":"12601","type":"Disease","text":["mydriasis"],"offsets":[[332,341]],"normalized":[{"db_name":"MESH","db_id":"D015878"}]},{"id":"12602","type":"Disease","text":["tremor"],"offsets":[[343,349]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"12603","type":"Disease","text":["clonic-tonic 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{"id":"12734","document_id":"6216862","passages":[{"id":"12735","type":"title","text":["Multiple side effects of penicillamine therapy in one patient with rheumatoid arthritis."],"offsets":[[0,88]]},{"id":"12736","type":"abstract","text":["Skin rashes, proteinuria, systemic lupus erythematosus, polymyositis and myasthenia gravis have all been recorded as complications of penicillamine therapy in patients with rheumatoid arthritis. A patient who had developed all 5 is now described. The skin lesion resembled elastosis perforans serpiginosa, which has been reported as a rare side effect in patients with Wilson's disease but not in patients with rheumatoid arthritis treated with penicillamine."],"offsets":[[89,548]]}],"entities":[{"id":"12737","type":"Chemical","text":["penicillamine"],"offsets":[[25,38]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"12738","type":"Disease","text":["rheumatoid arthritis"],"offsets":[[67,87]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"12739","type":"Disease","text":["Skin rashes"],"offsets":[[89,100]],"normalized":[{"db_name":"MESH","db_id":"D005076"}]},{"id":"12740","type":"Disease","text":["proteinuria"],"offsets":[[102,113]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"12741","type":"Disease","text":["systemic lupus erythematosus"],"offsets":[[115,143]],"normalized":[{"db_name":"MESH","db_id":"D008180"}]},{"id":"12742","type":"Disease","text":["polymyositis"],"offsets":[[145,157]],"normalized":[{"db_name":"MESH","db_id":"D017285"}]},{"id":"12743","type":"Disease","text":["myasthenia gravis"],"offsets":[[162,179]],"normalized":[{"db_name":"MESH","db_id":"D009157"}]},{"id":"12744","type":"Chemical","text":["penicillamine"],"offsets":[[223,236]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"12745","type":"Disease","text":["rheumatoid arthritis"],"offsets":[[262,282]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"12746","type":"Disease","text":["skin lesion"],"offsets":[[340,351]],"normalized":[{"db_name":"MESH","db_id":"D012871"}]},{"id":"12747","type":"Disease","text":["elastosis perforans serpiginosa"],"offsets":[[362,393]],"normalized":[{"db_name":"MESH","db_id":"C536202"}]},{"id":"12748","type":"Disease","text":["Wilson's disease"],"offsets":[[458,474]],"normalized":[{"db_name":"MESH","db_id":"D006527"}]},{"id":"12749","type":"Disease","text":["rheumatoid arthritis"],"offsets":[[500,520]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"12750","type":"Chemical","text":["penicillamine"],"offsets":[[534,547]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]}],"events":[],"coreferences":[],"relations":[{"id":"12751","type":"CID","arg1_id":"12737","arg2_id":"12743","normalized":[]},{"id":"12752","type":"CID","arg1_id":"12744","arg2_id":"12743","normalized":[]},{"id":"12753","type":"CID","arg1_id":"12750","arg2_id":"12743","normalized":[]},{"id":"12754","type":"CID","arg1_id":"12737","arg2_id":"12740","normalized":[]},{"id":"12755","type":"CID","arg1_id":"12744","arg2_id":"12740","normalized":[]},{"id":"12756","type":"CID","arg1_id":"12750","arg2_id":"12740","normalized":[]},{"id":"12757","type":"CID","arg1_id":"12737","arg2_id":"12739","normalized":[]},{"id":"12758","type":"CID","arg1_id":"12744","arg2_id":"12739","normalized":[]},{"id":"12759","type":"CID","arg1_id":"12750","arg2_id":"12739","normalized":[]},{"id":"12760","type":"CID","arg1_id":"12737","arg2_id":"12742","normalized":[]},{"id":"12761","type":"CID","arg1_id":"12744","arg2_id":"12742","normalized":[]},{"id":"12762","type":"CID","arg1_id":"12750","arg2_id":"12742","normalized":[]},{"id":"12763","type":"CID","arg1_id":"12737","arg2_id":"12741","normalized":[]},{"id":"12764","type":"CID","arg1_id":"12744","arg2_id":"12741","normalized":[]},{"id":"12765","type":"CID","arg1_id":"12750","arg2_id":"12741","normalized":[]}]}
{"id":"12766","document_id":"2004","passages":[{"id":"12767","type":"title","text":["Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs."],"offsets":[[0,94]]},{"id":"12768","type":"abstract","text":["Eight patients had cardiac manifestations that were life-threatening in five while taking psychotropic drugs, either phenothiazines or tricyclic antidepressants. Although most patients were receiving several drugs, Mellaril (thioridazine) appeared to be responsible for five cases of ventricular tachycardia, one of which was fatal in a 35 year old woman. Supraventricular tachycardia developed in one patient receiving Thorazine (chlorpromazine). Aventyl (nortriptyline) and Elavil (amitriptyline) each produced left bundle branch block in a 73 year old woman. Electrocardiographic T and U wave abnormalities were present in most patients. The ventricular arrhythmias responded to intravenous administration of lidocaine and to direct current electric shock; ventricular pacing was required in some instances and intravenous administration of propranolol combined with ventricular pacing in one. The tachyarrhythmias generally subsided within 48 hours after administration of the drugs was stopped. Five of the eight patients were 50 years of age or younger; only one clearly had antecedent heart disease. Major cardiac arrhythmias are a potential hazard in patients without heart disease who are receiving customary therapeutic doses of psychotropic drugs. A prospective clinical trial is suggested to quantify the risk of cardiac complications to patients receiving phenothiazines or tricyclic antidepressant drugs."],"offsets":[[95,1513]]}],"entities":[{"id":"12769","type":"Disease","text":["cardiac arrhythmias"],"offsets":[[33,52]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"12770","type":"Chemical","text":["phenothiazines"],"offsets":[[212,226]],"normalized":[{"db_name":"MESH","db_id":"D010640"}]},{"id":"12771","type":"Chemical","text":["Mellaril"],"offsets":[[310,318]],"normalized":[{"db_name":"MESH","db_id":"D013881"}]},{"id":"12772","type":"Chemical","text":["thioridazine"],"offsets":[[320,332]],"normalized":[{"db_name":"MESH","db_id":"D013881"}]},{"id":"12773","type":"Disease","text":["ventricular tachycardia"],"offsets":[[379,402]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"12774","type":"Disease","text":["Supraventricular tachycardia"],"offsets":[[451,479]],"normalized":[{"db_name":"MESH","db_id":"D013617"}]},{"id":"12775","type":"Chemical","text":["Thorazine"],"offsets":[[515,524]],"normalized":[{"db_name":"MESH","db_id":"D002746"}]},{"id":"12776","type":"Chemical","text":["chlorpromazine"],"offsets":[[526,540]],"normalized":[{"db_name":"MESH","db_id":"D002746"}]},{"id":"12777","type":"Chemical","text":["Aventyl"],"offsets":[[543,550]],"normalized":[{"db_name":"MESH","db_id":"D009661"}]},{"id":"12778","type":"Chemical","text":["nortriptyline"],"offsets":[[552,565]],"normalized":[{"db_name":"MESH","db_id":"D009661"}]},{"id":"12779","type":"Chemical","text":["Elavil"],"offsets":[[571,577]],"normalized":[{"db_name":"MESH","db_id":"D000639"}]},{"id":"12780","type":"Chemical","text":["amitriptyline"],"offsets":[[579,592]],"normalized":[{"db_name":"MESH","db_id":"D000639"}]},{"id":"12781","type":"Disease","text":["left bundle branch block"],"offsets":[[608,632]],"normalized":[{"db_name":"MESH","db_id":"D002037"}]},{"id":"12782","type":"Disease","text":["ventricular arrhythmias"],"offsets":[[740,763]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"12783","type":"Chemical","text":["lidocaine"],"offsets":[[807,816]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"12784","type":"Chemical","text":["propranolol"],"offsets":[[939,950]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"12785","type":"Disease","text":["tachyarrhythmias"],"offsets":[[996,1012]],"normalized":[{"db_name":"MESH","db_id":"D013610"}]},{"id":"12786","type":"Disease","text":["heart disease"],"offsets":[[1187,1200]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"12787","type":"Disease","text":["cardiac arrhythmias"],"offsets":[[1208,1227]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"12788","type":"Disease","text":["heart disease"],"offsets":[[1271,1284]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"12789","type":"Disease","text":["cardiac complications"],"offsets":[[1420,1441]],"normalized":[{"db_name":"MESH","db_id":"D005117"}]},{"id":"12790","type":"Chemical","text":["phenothiazines"],"offsets":[[1464,1478]],"normalized":[{"db_name":"MESH","db_id":"D010640"}]}],"events":[],"coreferences":[],"relations":[{"id":"12791","type":"CID","arg1_id":"12771","arg2_id":"12774","normalized":[]},{"id":"12792","type":"CID","arg1_id":"12772","arg2_id":"12774","normalized":[]},{"id":"12793","type":"CID","arg1_id":"12777","arg2_id":"12781","normalized":[]},{"id":"12794","type":"CID","arg1_id":"12778","arg2_id":"12781","normalized":[]},{"id":"12795","type":"CID","arg1_id":"12771","arg2_id":"12773","normalized":[]},{"id":"12796","type":"CID","arg1_id":"12772","arg2_id":"12773","normalized":[]},{"id":"12797","type":"CID","arg1_id":"12779","arg2_id":"12781","normalized":[]},{"id":"12798","type":"CID","arg1_id":"12780","arg2_id":"12781","normalized":[]}]}
{"id":"12799","document_id":"6118280","passages":[{"id":"12800","type":"title","text":["Serotonergic drugs, benzodiazepines and baclofen block muscimol-induced myoclonic jerks in a strain of mice."],"offsets":[[0,108]]},{"id":"12801","type":"abstract","text":["In male Swiss mice, muscimol produced myoclonic jerks. A 3 mg\/kg (i.p.) dose induced this response in all of the mice tested and the peak response of 73 jerks per min was observed between 27 and 45 min. Increasing the brain serotonin levels by the administration of 5-hydroxytryptophan (80-160 mg\/kg) in combination with a peripheral decarboxylase inhibitor resulted in an inhibition of the muscimol effect. However, in a similar experiment l-dopa (80-160 mg\/kg) was without effect. In doses of 3-10 mg\/kg, the serotonin receptor agonist MK-212 caused a dose-dependent blockade of the response of muscimol. Of the benzodiazepines, clonazepam (0.1-0.3 mg\/kg) was found to be several fold more potent than diazepam (0.3-3 mg\/kg) in blocking the myoclonic jerks. While (-)-baclofen (1-3 mg\/kg) proved to be an effective antagonist of muscimol, its (+)-isomer (5-20 mg\/kg) lacked this property. Considering the fact that 5-HTP and the benzodiazepines have been found to be beneficial in the management of clinical myoclonus, the muscimol-induced myoclonus seems to be a satisfactory animal model that may prove useful for the development of new drug treatments for this condition. Our present study indicated the possible value of MK-212 and (-)-baclofen in the management of clinical myoclonus."],"offsets":[[109,1400]]}],"entities":[{"id":"12802","type":"Chemical","text":["benzodiazepines"],"offsets":[[20,35]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]},{"id":"12803","type":"Chemical","text":["baclofen"],"offsets":[[40,48]],"normalized":[{"db_name":"MESH","db_id":"D001418"}]},{"id":"12804","type":"Chemical","text":["muscimol"],"offsets":[[55,63]],"normalized":[{"db_name":"MESH","db_id":"D009118"}]},{"id":"12805","type":"Disease","text":["myoclonic jerks"],"offsets":[[72,87]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"12806","type":"Chemical","text":["muscimol"],"offsets":[[129,137]],"normalized":[{"db_name":"MESH","db_id":"D009118"}]},{"id":"12807","type":"Disease","text":["myoclonic 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jerks"],"offsets":[[852,867]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"12819","type":"Chemical","text":["baclofen"],"offsets":[[879,887]],"normalized":[{"db_name":"MESH","db_id":"D001418"}]},{"id":"12820","type":"Chemical","text":["muscimol"],"offsets":[[940,948]],"normalized":[{"db_name":"MESH","db_id":"D009118"}]},{"id":"12821","type":"Chemical","text":["5-HTP"],"offsets":[[1026,1031]],"normalized":[{"db_name":"MESH","db_id":"D006916"}]},{"id":"12822","type":"Chemical","text":["benzodiazepines"],"offsets":[[1040,1055]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]},{"id":"12823","type":"Disease","text":["myoclonus"],"offsets":[[1119,1128]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"12824","type":"Chemical","text":["muscimol"],"offsets":[[1134,1142]],"normalized":[{"db_name":"MESH","db_id":"D009118"}]},{"id":"12825","type":"Disease","text":["myoclonus"],"offsets":[[1151,1160]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"12826","type":"Chemical","text":["MK-212"],"offsets":[[1336,1342]],"normalized":[{"db_name":"MESH","db_id":"C014896"}]},{"id":"12827","type":"Chemical","text":["baclofen"],"offsets":[[1351,1359]],"normalized":[{"db_name":"MESH","db_id":"D001418"}]},{"id":"12828","type":"Disease","text":["myoclonus"],"offsets":[[1390,1399]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]}],"events":[],"coreferences":[],"relations":[{"id":"12829","type":"CID","arg1_id":"12804","arg2_id":"12805","normalized":[]},{"id":"12830","type":"CID","arg1_id":"12804","arg2_id":"12807","normalized":[]},{"id":"12831","type":"CID","arg1_id":"12804","arg2_id":"12818","normalized":[]},{"id":"12832","type":"CID","arg1_id":"12804","arg2_id":"12823","normalized":[]},{"id":"12833","type":"CID","arg1_id":"12804","arg2_id":"12825","normalized":[]},{"id":"12834","type":"CID","arg1_id":"12804","arg2_id":"12828","normalized":[]},{"id":"12835","type":"CID","arg1_id":"12806","arg2_id":"12805","normalized":[]},{"id":"12836","type":"CID","arg1_id":"12806","arg2_id":"12807","normalized":[]},{"id":"12837","type":"CID","arg1_id":"12806","arg2_id":"12818","normalized":[]},{"id":"12838","type":"CID","arg1_id":"12806","arg2_id":"12823","normalized":[]},{"id":"12839","type":"CID","arg1_id":"12806","arg2_id":"12825","normalized":[]},{"id":"12840","type":"CID","arg1_id":"12806","arg2_id":"12828","normalized":[]},{"id":"12841","type":"CID","arg1_id":"12810","arg2_id":"12805","normalized":[]},{"id":"12842","type":"CID","arg1_id":"12810","arg2_id":"12807","normalized":[]},{"id":"12843","type":"CID","arg1_id":"12810","arg2_id":"12818","normalized":[]},{"id":"12844","type":"CID","arg1_id":"12810","arg2_id":"12823","normalized":[]},{"id":"12845","type":"CID","arg1_id":"12810","arg2_id":"12825","normalized":[]},{"id":"12846","type":"CID","arg1_id":"12810","arg2_id":"12828","normalized":[]},{"id":"12847","type":"CID","arg1_id":"12814","arg2_id":"12805","normalized":[]},{"id":"12848","type":"CID","arg1_id":"12814","arg2_id":"12807","normalized":[]},{"id":"12849","type":"CID","arg1_id":"12814","arg2_id":"12818","normalized":[]},{"id":"12850","type":"CID","arg1_id":"12814","arg2_id":"12823","normalized":[]},{"id":"12851","type":"CID","arg1_id":"12814","arg2_id":"12825","normalized":[]},{"id":"12852","type":"CID","arg1_id":"12814","arg2_id":"12828","normalized":[]},{"id":"12853","type":"CID","arg1_id":"12820","arg2_id":"12805","normalized":[]},{"id":"12854","type":"CID","arg1_id":"12820","arg2_id":"12807","normalized":[]},{"id":"12855","type":"CID","arg1_id":"12820","arg2_id":"12818","normalized":[]},{"id":"12856","type":"CID","arg1_id":"12820","arg2_id":"12823","normalized":[]},{"id":"12857","type":"CID","arg1_id":"12820","arg2_id":"12825","normalized":[]},{"id":"12858","type":"CID","arg1_id":"12820","arg2_id":"12828","normalized":[]},{"id":"12859","type":"CID","arg1_id":"12824","arg2_id":"12805","normalized":[]},{"id":"12860","type":"CID","arg1_id":"12824","arg2_id":"12807","normalized":[]},{"id":"12861","type":"CID","arg1_id":"12824","arg2_id":"12818","normalized":[]},{"id":"12862","type":"CID","arg1_id":"12824","arg2_id":"12823","normalized":[]},{"id":"12863","type":"CID","arg1_id":"12824","arg2_id":"12825","normalized":[]},{"id":"12864","type":"CID","arg1_id":"12824","arg2_id":"12828","normalized":[]}]}
{"id":"12865","document_id":"3703509","passages":[{"id":"12866","type":"title","text":["Hyperglycemic acidotic coma and death in Kearns-Sayre syndrome."],"offsets":[[0,63]]},{"id":"12867","type":"abstract","text":["This paper presents the clinical and metabolic findings in two young boys with long-standing Kearns-Sayre syndrome. Following short exposure to oral prednisone, both boys developed lethargy, increasing somnolence, polydipsia, polyphagia, and polyuria. Both presented in the emergency room with profound coma, hypotension, severe hyperglycemia, and acidosis. Nonketotic lactic acidosis was present in one and ketosis without a known serum lactate level was present in the other. Respiratory failure rapidly ensued and both patients expired in spite of efforts at resuscitation. We believe these two cases represent a newly described and catastrophic metabolic-endocrine failure in the Kearns-Sayre syndrome."],"offsets":[[64,770]]}],"entities":[{"id":"12868","type":"Disease","text":["Hyperglycemic acidotic coma"],"offsets":[[0,27]],"normalized":[{"db_name":"MESH","db_id":"D006943"},{"db_name":"MESH","db_id":"D000140"},{"db_name":"MESH","db_id":"D003128"}]},{"id":"12869","type":"Disease","text":["Hyperglycemic"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D006943"}]},{"id":"12870","type":"Disease","text":["acidotic"],"offsets":[[14,22]],"normalized":[{"db_name":"MESH","db_id":"D000140"}]},{"id":"12871","type":"Disease","text":["coma"],"offsets":[[23,27]],"normalized":[{"db_name":"MESH","db_id":"D003128"}]},{"id":"12872","type":"Disease","text":["Kearns-Sayre syndrome"],"offsets":[[41,62]],"normalized":[{"db_name":"MESH","db_id":"D007625"}]},{"id":"12873","type":"Disease","text":["Kearns-Sayre syndrome"],"offsets":[[157,178]],"normalized":[{"db_name":"MESH","db_id":"D007625"}]},{"id":"12874","type":"Chemical","text":["prednisone"],"offsets":[[213,223]],"normalized":[{"db_name":"MESH","db_id":"D011241"}]},{"id":"12875","type":"Disease","text":["lethargy"],"offsets":[[245,253]],"normalized":[{"db_name":"MESH","db_id":"D053609"}]},{"id":"12876","type":"Disease","text":["somnolence"],"offsets":[[266,276]],"normalized":[{"db_name":"MESH","db_id":"D006970"}]},{"id":"12877","type":"Disease","text":["polydipsia"],"offsets":[[278,288]],"normalized":[{"db_name":"MESH","db_id":"D059606"}]},{"id":"12878","type":"Disease","text":["polyphagia"],"offsets":[[290,300]],"normalized":[{"db_name":"MESH","db_id":"D006963"}]},{"id":"12879","type":"Disease","text":["polyuria"],"offsets":[[306,314]],"normalized":[{"db_name":"MESH","db_id":"D011141"}]},{"id":"12880","type":"Disease","text":["coma"],"offsets":[[367,371]],"normalized":[{"db_name":"MESH","db_id":"D003128"}]},{"id":"12881","type":"Disease","text":["hypotension"],"offsets":[[373,384]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"12882","type":"Disease","text":["hyperglycemia"],"offsets":[[393,406]],"normalized":[{"db_name":"MESH","db_id":"D006943"}]},{"id":"12883","type":"Disease","text":["acidosis"],"offsets":[[412,420]],"normalized":[{"db_name":"MESH","db_id":"D000138"}]},{"id":"12884","type":"Disease","text":["lactic acidosis"],"offsets":[[433,448]],"normalized":[{"db_name":"MESH","db_id":"D000140"}]},{"id":"12885","type":"Disease","text":["ketosis"],"offsets":[[472,479]],"normalized":[{"db_name":"MESH","db_id":"D007662"}]},{"id":"12886","type":"Chemical","text":["lactate"],"offsets":[[502,509]],"normalized":[{"db_name":"MESH","db_id":"D019344"}]},{"id":"12887","type":"Disease","text":["Respiratory failure"],"offsets":[[542,561]],"normalized":[{"db_name":"MESH","db_id":"D012131"}]},{"id":"12888","type":"Disease","text":["metabolic-endocrine failure"],"offsets":[[713,740]],"normalized":[]},{"id":"12889","type":"Disease","text":["Kearns-Sayre syndrome"],"offsets":[[748,769]],"normalized":[{"db_name":"MESH","db_id":"D007625"}]}],"events":[],"coreferences":[],"relations":[{"id":"12890","type":"CID","arg1_id":"12874","arg2_id":"12885","normalized":[]},{"id":"12891","type":"CID","arg1_id":"12874","arg2_id":"12881","normalized":[]},{"id":"12892","type":"CID","arg1_id":"12874","arg2_id":"12868","normalized":[]},{"id":"12893","type":"CID","arg1_id":"12874","arg2_id":"12871","normalized":[]},{"id":"12894","type":"CID","arg1_id":"12874","arg2_id":"12880","normalized":[]},{"id":"12895","type":"CID","arg1_id":"12874","arg2_id":"12868","normalized":[]},{"id":"12896","type":"CID","arg1_id":"12874","arg2_id":"12870","normalized":[]},{"id":"12897","type":"CID","arg1_id":"12874","arg2_id":"12884","normalized":[]},{"id":"12898","type":"CID","arg1_id":"12874","arg2_id":"12868","normalized":[]},{"id":"12899","type":"CID","arg1_id":"12874","arg2_id":"12869","normalized":[]},{"id":"12900","type":"CID","arg1_id":"12874","arg2_id":"12882","normalized":[]}]}
{"id":"12901","document_id":"20683499","passages":[{"id":"12902","type":"title","text":["Effects of active constituents of Crocus sativus L., crocin on streptozocin-induced model of sporadic Alzheimer's disease in male rats."],"offsets":[[0,135]]},{"id":"12903","type":"abstract","text":["BACKGROUND: The involvement of water-soluble carotenoids, crocins, as the main and active components of Crocus sativus L. extract in learning and memory processes has been proposed. In the present study, the effect of crocins on sporadic Alzheimer's disease induced by intracerebroventricular (icv) streptozocin (STZ) in male rats was investigated. METHODS: Male adult Wistar rats (n = 90 and 260-290 g) were divided into 1, control; 2 and 3, crocins (15 and 30 mg\/kg); 4, STZ; 5 and 6, STZ + crocins (15 and 30 mg\/kg) groups. In Alzheimer's disease groups, rats were injected with STZ-icv bilaterally (3 mg\/kg) in first day and 3 days later, a similar STZ-icv application was repeated. In STZ + crocin animal groups, crocin was applied in doses of 15 and 30 mg\/kg, i.p., one day pre-surgery and continued for three weeks. Prescription of crocin in each dose was repeated once for two days. However, the learning and memory performance was assessed using passive avoidance paradigm, and for spatial cognition evaluation, Y-maze task was used. RESULTS: It was found out that crocin (30 mg\/kg)-treated STZ-injected rats show higher correct choices and lower errors in Y-maze than vehicle-treated STZ-injected rats. In addition, crocin in the mentioned dose could significantly attenuated learning and memory impairment in treated STZ-injected group in passive avoidance test. CONCLUSION: Therefore, these results demonstrate the effectiveness of crocin (30 mg\/kg) in antagonizing the cognitive deficits caused by STZ-icv in rats and its potential in the treatment of neurodegenerative diseases such as Alzheimer's disease."],"offsets":[[136,1756]]}],"entities":[{"id":"12904","type":"Chemical","text":["crocin"],"offsets":[[53,59]],"normalized":[{"db_name":"MESH","db_id":"C029036"}]},{"id":"12905","type":"Chemical","text":["streptozocin"],"offsets":[[63,75]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"12906","type":"Disease","text":["Alzheimer's disease"],"offsets":[[102,121]],"normalized":[{"db_name":"MESH","db_id":"D000544"}]},{"id":"12907","type":"Chemical","text":["carotenoids"],"offsets":[[181,192]],"normalized":[{"db_name":"MESH","db_id":"D002338"}]},{"id":"12908","type":"Chemical","text":["crocins"],"offsets":[[194,201]],"normalized":[{"db_name":"MESH","db_id":"C029036"}]},{"id":"12909","type":"Chemical","text":["crocins"],"offsets":[[354,361]],"normalized":[{"db_name":"MESH","db_id":"C029036"}]},{"id":"12910","type":"Disease","text":["Alzheimer's disease"],"offsets":[[374,393]],"normalized":[{"db_name":"MESH","db_id":"D000544"}]},{"id":"12911","type":"Chemical","text":["streptozocin"],"offsets":[[435,447]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"12912","type":"Chemical","text":["STZ"],"offsets":[[449,452]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"12913","type":"Chemical","text":["crocins"],"offsets":[[579,586]],"normalized":[{"db_name":"MESH","db_id":"C029036"}]},{"id":"12914","type":"Chemical","text":["STZ"],"offsets":[[609,612]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"12915","type":"Chemical","text":["STZ"],"offsets":[[623,626]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"12916","type":"Chemical","text":["crocins"],"offsets":[[629,636]],"normalized":[{"db_name":"MESH","db_id":"C029036"}]},{"id":"12917","type":"Disease","text":["Alzheimer's disease"],"offsets":[[666,685]],"normalized":[{"db_name":"MESH","db_id":"D000544"}]},{"id":"12918","type":"Chemical","text":["STZ"],"offsets":[[718,721]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"12919","type":"Chemical","text":["STZ"],"offsets":[[789,792]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"12920","type":"Chemical","text":["STZ"],"offsets":[[826,829]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"12921","type":"Chemical","text":["crocin"],"offsets":[[832,838]],"normalized":[{"db_name":"MESH","db_id":"C029036"}]},{"id":"12922","type":"Chemical","text":["crocin"],"offsets":[[854,860]],"normalized":[{"db_name":"MESH","db_id":"C029036"}]},{"id":"12923","type":"Chemical","text":["crocin"],"offsets":[[975,981]],"normalized":[{"db_name":"MESH","db_id":"C029036"}]},{"id":"12924","type":"Chemical","text":["crocin"],"offsets":[[1210,1216]],"normalized":[{"db_name":"MESH","db_id":"C029036"}]},{"id":"12925","type":"Chemical","text":["STZ"],"offsets":[[1236,1239]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"12926","type":"Chemical","text":["STZ"],"offsets":[[1330,1333]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"12927","type":"Chemical","text":["crocin"],"offsets":[[1362,1368]],"normalized":[{"db_name":"MESH","db_id":"C029036"}]},{"id":"12928","type":"Disease","text":["learning and memory impairment"],"offsets":[[1422,1452]],"normalized":[{"db_name":"MESH","db_id":"D007859"},{"db_name":"MESH","db_id":"D008569"}]},{"id":"12929","type":"Disease","text":["learning","impairment"],"offsets":[[1422,1430],[1442,1452]],"normalized":[{"db_name":"MESH","db_id":"D007859"}]},{"id":"12930","type":"Disease","text":["memory impairment"],"offsets":[[1435,1452]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"12931","type":"Chemical","text":["STZ"],"offsets":[[1464,1467]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"12932","type":"Chemical","text":["crocin"],"offsets":[[1580,1586]],"normalized":[{"db_name":"MESH","db_id":"C029036"}]},{"id":"12933","type":"Disease","text":["cognitive deficits"],"offsets":[[1618,1636]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"12934","type":"Chemical","text":["STZ"],"offsets":[[1647,1650]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"12935","type":"Disease","text":["neurodegenerative diseases"],"offsets":[[1701,1727]],"normalized":[{"db_name":"MESH","db_id":"D019636"}]},{"id":"12936","type":"Disease","text":["Alzheimer's 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{"id":"12997","document_id":"20466178","passages":[{"id":"12998","type":"title","text":["Rosaceiform dermatitis associated with topical tacrolimus treatment."],"offsets":[[0,68]]},{"id":"12999","type":"abstract","text":["We describe herein 3 patients who developed rosacea-like dermatitis eruptions while using 0.03% or 0.1% tacrolimus ointment for facial dermatitis. Skin biopsy specimens showed telangiectasia and noncaseating epithelioid granulomatous tissue formation in the papillary to mid dermis. Continuous topical use of immunomodulators such as tacrolimus or pimecrolimus should be regarded as a potential cause of rosaceiform dermatitis, although many cases have not been reported."],"offsets":[[69,540]]}],"entities":[{"id":"13000","type":"Disease","text":["dermatitis"],"offsets":[[12,22]],"normalized":[{"db_name":"MESH","db_id":"D003872"}]},{"id":"13001","type":"Chemical","text":["tacrolimus"],"offsets":[[47,57]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"13002","type":"Disease","text":["rosacea"],"offsets":[[113,120]],"normalized":[{"db_name":"MESH","db_id":"D012393"}]},{"id":"13003","type":"Disease","text":["dermatitis"],"offsets":[[126,136]],"normalized":[{"db_name":"MESH","db_id":"D003872"}]},{"id":"13004","type":"Disease","text":["eruptions"],"offsets":[[137,146]],"normalized":[{"db_name":"MESH","db_id":"D003875"}]},{"id":"13005","type":"Chemical","text":["tacrolimus"],"offsets":[[173,183]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"13006","type":"Disease","text":["facial dermatitis"],"offsets":[[197,214]],"normalized":[{"db_name":"MESH","db_id":"D005148"}]},{"id":"13007","type":"Disease","text":["telangiectasia"],"offsets":[[245,259]],"normalized":[{"db_name":"MESH","db_id":"D013684"}]},{"id":"13008","type":"Chemical","text":["tacrolimus"],"offsets":[[403,413]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"13009","type":"Chemical","text":["pimecrolimus"],"offsets":[[417,429]],"normalized":[{"db_name":"MESH","db_id":"C117268"}]},{"id":"13010","type":"Disease","text":["dermatitis"],"offsets":[[485,495]],"normalized":[{"db_name":"MESH","db_id":"D003872"}]}],"events":[],"coreferences":[],"relations":[{"id":"13011","type":"CID","arg1_id":"13009","arg2_id":"13000","normalized":[]},{"id":"13012","type":"CID","arg1_id":"13009","arg2_id":"13003","normalized":[]},{"id":"13013","type":"CID","arg1_id":"13009","arg2_id":"13010","normalized":[]},{"id":"13014","type":"CID","arg1_id":"13009","arg2_id":"13004","normalized":[]},{"id":"13015","type":"CID","arg1_id":"13009","arg2_id":"13007","normalized":[]}]}
{"id":"13016","document_id":"19944736","passages":[{"id":"13017","type":"title","text":["A novel animal model to evaluate the ability of a drug delivery system to promote the passage through the BBB."],"offsets":[[0,110]]},{"id":"13018","type":"abstract","text":["The purpose of this investigation was to explore the potentiality of a novel animal model to be used for the in vivo evaluation of the ability of a drug delivery system to promote the passage through the blood-brain barrier (BBB) and\/or to improve the brain localization of a bioactive compound. A Tween 80-coated poly-L-lactid acid nanoparticles was used as a model of colloidal drug delivery system, able to trespass the BBB. Tacrine, administered in LiCl pre-treated rats, induces electrocorticographic seizures and delayed hippocampal damage. The toxic effects of tacrine-loaded poly-L-lactid acid nanoparticles (5mg\/kg), a saline solution of tacrine (5mg\/kg) and an empty colloidal nanoparticle suspension were compared following i.p. administration in LiCl-pre-treated Wistar rats. All the animals treated with tacrine-loaded nanoparticles showed an earlier outcome of CNS adverse symptoms, i.e. epileptic onset, with respect to those animals treated with the free compound (10 min vs. 22 min respectively). In addition, tacrine-loaded nanoparticles administration induced damage of neuronal cells in CA1 field of the hippocampus in all treated animals, while the saline solution of tacrine only in 60% of animals. Empty nanoparticles provided similar results to control (saline-treated) group of animals. In conclusion, the evaluation of time-to-onset of symptoms and the severity of neurodegenerative processes induced by the tacrine-lithium model of epilepsy in the rat, could be used to evaluate preliminarily the capability of a drug delivery system to trespass (or not) the BBB in vivo."],"offsets":[[111,1709]]}],"entities":[{"id":"13019","type":"Chemical","text":["poly-L-lactid acid"],"offsets":[[425,443]],"normalized":[]},{"id":"13020","type":"Chemical","text":["Tacrine"],"offsets":[[539,546]],"normalized":[{"db_name":"MESH","db_id":"D013619"}]},{"id":"13021","type":"Chemical","text":["LiCl"],"offsets":[[564,568]],"normalized":[{"db_name":"MESH","db_id":"D018021"}]},{"id":"13022","type":"Disease","text":["seizures"],"offsets":[[617,625]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"13023","type":"Disease","text":["hippocampal damage"],"offsets":[[638,656]],"normalized":[{"db_name":"MESH","db_id":"D001930"}]},{"id":"13024","type":"Chemical","text":["tacrine"],"offsets":[[679,686]],"normalized":[{"db_name":"MESH","db_id":"D013619"}]},{"id":"13025","type":"Chemical","text":["poly-L-lactid acid"],"offsets":[[694,712]],"normalized":[]},{"id":"13026","type":"Chemical","text":["tacrine"],"offsets":[[758,765]],"normalized":[{"db_name":"MESH","db_id":"D013619"}]},{"id":"13027","type":"Chemical","text":["LiCl"],"offsets":[[869,873]],"normalized":[{"db_name":"MESH","db_id":"D018021"}]},{"id":"13028","type":"Chemical","text":["tacrine"],"offsets":[[928,935]],"normalized":[{"db_name":"MESH","db_id":"D013619"}]},{"id":"13029","type":"Disease","text":["epileptic"],"offsets":[[1013,1022]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"13030","type":"Chemical","text":["tacrine"],"offsets":[[1138,1145]],"normalized":[{"db_name":"MESH","db_id":"D013619"}]},{"id":"13031","type":"Disease","text":["damage of neuronal cells"],"offsets":[[1190,1214]],"normalized":[{"db_name":"MESH","db_id":"D001930"}]},{"id":"13032","type":"Chemical","text":["tacrine"],"offsets":[[1300,1307]],"normalized":[{"db_name":"MESH","db_id":"D013619"}]},{"id":"13033","type":"Chemical","text":["tacrine"],"offsets":[[1545,1552]],"normalized":[{"db_name":"MESH","db_id":"D013619"}]},{"id":"13034","type":"Chemical","text":["lithium"],"offsets":[[1553,1560]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"13035","type":"Disease","text":["epilepsy"],"offsets":[[1570,1578]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]}],"events":[],"coreferences":[],"relations":[{"id":"13036","type":"CID","arg1_id":"13021","arg2_id":"13023","normalized":[]},{"id":"13037","type":"CID","arg1_id":"13021","arg2_id":"13031","normalized":[]},{"id":"13038","type":"CID","arg1_id":"13027","arg2_id":"13023","normalized":[]},{"id":"13039","type":"CID","arg1_id":"13027","arg2_id":"13031","normalized":[]},{"id":"13040","type":"CID","arg1_id":"13020","arg2_id":"13023","normalized":[]},{"id":"13041","type":"CID","arg1_id":"13020","arg2_id":"13031","normalized":[]},{"id":"13042","type":"CID","arg1_id":"13024","arg2_id":"13023","normalized":[]},{"id":"13043","type":"CID","arg1_id":"13024","arg2_id":"13031","normalized":[]},{"id":"13044","type":"CID","arg1_id":"13026","arg2_id":"13023","normalized":[]},{"id":"13045","type":"CID","arg1_id":"13026","arg2_id":"13031","normalized":[]},{"id":"13046","type":"CID","arg1_id":"13028","arg2_id":"13023","normalized":[]},{"id":"13047","type":"CID","arg1_id":"13028","arg2_id":"13031","normalized":[]},{"id":"13048","type":"CID","arg1_id":"13030","arg2_id":"13023","normalized":[]},{"id":"13049","type":"CID","arg1_id":"13030","arg2_id":"13031","normalized":[]},{"id":"13050","type":"CID","arg1_id":"13032","arg2_id":"13023","normalized":[]},{"id":"13051","type":"CID","arg1_id":"13032","arg2_id":"13031","normalized":[]},{"id":"13052","type":"CID","arg1_id":"13033","arg2_id":"13023","normalized":[]},{"id":"13053","type":"CID","arg1_id":"13033","arg2_id":"13031","normalized":[]},{"id":"13054","type":"CID","arg1_id":"13021","arg2_id":"13022","normalized":[]},{"id":"13055","type":"CID","arg1_id":"13027","arg2_id":"13022","normalized":[]},{"id":"13056","type":"CID","arg1_id":"13020","arg2_id":"13022","normalized":[]},{"id":"13057","type":"CID","arg1_id":"13024","arg2_id":"13022","normalized":[]},{"id":"13058","type":"CID","arg1_id":"13026","arg2_id":"13022","normalized":[]},{"id":"13059","type":"CID","arg1_id":"13028","arg2_id":"13022","normalized":[]},{"id":"13060","type":"CID","arg1_id":"13030","arg2_id":"13022","normalized":[]},{"id":"13061","type":"CID","arg1_id":"13032","arg2_id":"13022","normalized":[]},{"id":"13062","type":"CID","arg1_id":"13033","arg2_id":"13022","normalized":[]}]}
{"id":"13063","document_id":"19721134","passages":[{"id":"13064","type":"title","text":["The antiarrhythmic effect and possible ionic mechanisms of pilocarpine on animal models."],"offsets":[[0,88]]},{"id":"13065","type":"abstract","text":["This study was designed to evaluate the effects of pilocarpine and explore the underlying ionic mechanism, using both aconitine-induced rat and ouabain-induced guinea pig arrhythmia models. Confocal microscopy was used to measure intracellular free-calcium concentrations ([Ca(2+)](i)) in isolated myocytes. The current data showed that pilocarpine significantly delayed onset of arrhythmias, decreased the time course of ventricular tachycardia and fibrillation, reduced arrhythmia score, and increased the survival time of arrhythmic rats and guinea pigs. [Ca(2+)](i) overload induced by aconitine or ouabain was reduced in isolated myocytes pretreated with pilocarpine. Moreover, M(3)-muscarinic acetylcholine receptor (mAChR) antagonist 4-DAMP (4-diphenylacetoxy-N-methylpiperidine-methiodide) partially abolished the beneficial effects of pilocarpine. These data suggest that pilocarpine produced antiarrhythmic actions on arrhythmic rat and guinea pig models induced by aconitine or ouabain via stimulating the cardiac M(3)-mAChR. The mechanism may be related to the improvement of Ca(2+) handling."],"offsets":[[89,1193]]}],"entities":[{"id":"13066","type":"Chemical","text":["pilocarpine"],"offsets":[[59,70]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"13067","type":"Chemical","text":["pilocarpine"],"offsets":[[140,151]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"13068","type":"Chemical","text":["aconitine"],"offsets":[[207,216]],"normalized":[{"db_name":"MESH","db_id":"D000157"}]},{"id":"13069","type":"Chemical","text":["ouabain"],"offsets":[[233,240]],"normalized":[{"db_name":"MESH","db_id":"D010042"}]},{"id":"13070","type":"Disease","text":["arrhythmia"],"offsets":[[260,270]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"13071","type":"Chemical","text":["calcium"],"offsets":[[338,345]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"13072","type":"Chemical","text":["Ca"],"offsets":[[363,365]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"13073","type":"Chemical","text":["pilocarpine"],"offsets":[[426,437]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"13074","type":"Disease","text":["arrhythmias"],"offsets":[[469,480]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"13075","type":"Disease","text":["ventricular tachycardia and fibrillation"],"offsets":[[511,551]],"normalized":[{"db_name":"MESH","db_id":"D017180"},{"db_name":"MESH","db_id":"D014693"}]},{"id":"13076","type":"Disease","text":["ventricular tachycardia"],"offsets":[[511,534]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"13077","type":"Disease","text":["ventricular","fibrillation"],"offsets":[[511,522],[539,551]],"normalized":[{"db_name":"MESH","db_id":"D014693"}]},{"id":"13078","type":"Disease","text":["arrhythmia"],"offsets":[[561,571]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"13079","type":"Disease","text":["arrhythmic"],"offsets":[[614,624]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"13080","type":"Chemical","text":["Ca"],"offsets":[[648,650]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"13081","type":"Chemical","text":["aconitine"],"offsets":[[679,688]],"normalized":[{"db_name":"MESH","db_id":"D000157"}]},{"id":"13082","type":"Chemical","text":["ouabain"],"offsets":[[692,699]],"normalized":[{"db_name":"MESH","db_id":"D010042"}]},{"id":"13083","type":"Chemical","text":["pilocarpine"],"offsets":[[749,760]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"13084","type":"Chemical","text":["acetylcholine"],"offsets":[[788,801]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"13085","type":"Chemical","text":["4-DAMP"],"offsets":[[830,836]],"normalized":[{"db_name":"MESH","db_id":"C042375"}]},{"id":"13086","type":"Chemical","text":["4-diphenylacetoxy-N-methylpiperidine-methiodide"],"offsets":[[838,885]],"normalized":[{"db_name":"MESH","db_id":"C042375"}]},{"id":"13087","type":"Chemical","text":["pilocarpine"],"offsets":[[933,944]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"13088","type":"Chemical","text":["pilocarpine"],"offsets":[[970,981]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"13089","type":"Disease","text":["arrhythmic"],"offsets":[[1017,1027]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"13090","type":"Chemical","text":["aconitine"],"offsets":[[1065,1074]],"normalized":[{"db_name":"MESH","db_id":"D000157"}]},{"id":"13091","type":"Chemical","text":["ouabain"],"offsets":[[1078,1085]],"normalized":[{"db_name":"MESH","db_id":"D010042"}]},{"id":"13092","type":"Chemical","text":["Ca"],"offsets":[[1177,1179]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]}],"events":[],"coreferences":[],"relations":[{"id":"13093","type":"CID","arg1_id":"13069","arg2_id":"13070","normalized":[]},{"id":"13094","type":"CID","arg1_id":"13069","arg2_id":"13074","normalized":[]},{"id":"13095","type":"CID","arg1_id":"13069","arg2_id":"13078","normalized":[]},{"id":"13096","type":"CID","arg1_id":"13069","arg2_id":"13079","normalized":[]},{"id":"13097","type":"CID","arg1_id":"13069","arg2_id":"13089","normalized":[]},{"id":"13098","type":"CID","arg1_id":"13082","arg2_id":"13070","normalized":[]},{"id":"13099","type":"CID","arg1_id":"13082","arg2_id":"13074","normalized":[]},{"id":"13100","type":"CID","arg1_id":"13082","arg2_id":"13078","normalized":[]},{"id":"13101","type":"CID","arg1_id":"13082","arg2_id":"13079","normalized":[]},{"id":"13102","type":"CID","arg1_id":"13082","arg2_id":"13089","normalized":[]},{"id":"13103","type":"CID","arg1_id":"13091","arg2_id":"13070","normalized":[]},{"id":"13104","type":"CID","arg1_id":"13091","arg2_id":"13074","normalized":[]},{"id":"13105","type":"CID","arg1_id":"13091","arg2_id":"13078","normalized":[]},{"id":"13106","type":"CID","arg1_id":"13091","arg2_id":"13079","normalized":[]},{"id":"13107","type":"CID","arg1_id":"13091","arg2_id":"13089","normalized":[]},{"id":"13108","type":"CID","arg1_id":"13068","arg2_id":"13070","normalized":[]},{"id":"13109","type":"CID","arg1_id":"13068","arg2_id":"13074","normalized":[]},{"id":"13110","type":"CID","arg1_id":"13068","arg2_id":"13078","normalized":[]},{"id":"13111","type":"CID","arg1_id":"13068","arg2_id":"13079","normalized":[]},{"id":"13112","type":"CID","arg1_id":"13068","arg2_id":"13089","normalized":[]},{"id":"13113","type":"CID","arg1_id":"13081","arg2_id":"13070","normalized":[]},{"id":"13114","type":"CID","arg1_id":"13081","arg2_id":"13074","normalized":[]},{"id":"13115","type":"CID","arg1_id":"13081","arg2_id":"13078","normalized":[]},{"id":"13116","type":"CID","arg1_id":"13081","arg2_id":"13079","normalized":[]},{"id":"13117","type":"CID","arg1_id":"13081","arg2_id":"13089","normalized":[]},{"id":"13118","type":"CID","arg1_id":"13090","arg2_id":"13070","normalized":[]},{"id":"13119","type":"CID","arg1_id":"13090","arg2_id":"13074","normalized":[]},{"id":"13120","type":"CID","arg1_id":"13090","arg2_id":"13078","normalized":[]},{"id":"13121","type":"CID","arg1_id":"13090","arg2_id":"13079","normalized":[]},{"id":"13122","type":"CID","arg1_id":"13090","arg2_id":"13089","normalized":[]}]}
{"id":"13123","document_id":"17786501","passages":[{"id":"13124","type":"title","text":["Disulfiram-induced transient optic and peripheral neuropathy: a case report."],"offsets":[[0,76]]},{"id":"13125","type":"abstract","text":["AIM: To report a case of optic and peripheral neuropathy after chronic use of disulfiram for alcohol dependence management. MATERIALS AND METHODS: A case report. RESULTS: A 57-year-old male presented with gradual loss of vision in both eyes with intermittent headaches for 2 months. He also complained of paraesthesia with numbness in both feet. His vision was 6\/15 and 2\/60 in the right and left eyes, respectively. Fundoscopy revealed bilaterally swollen optic nerve heads. Visual field testing confirmed bilateral central-caecal scotomata. He had been taking disulfiram for alcohol dependence for the preceding 3 years. Disulfiram discontinuation lead to an immediate symptomatic improvement. CONCLUSION: Physicians initiating long-term disulfiram therapy should be aware of these adverse effects. They should recommend annual ophthalmic reviews with visual field testing. Patients should be reassured with respect to the reversibility of these adverse effects."],"offsets":[[77,1041]]}],"entities":[{"id":"13126","type":"Chemical","text":["Disulfiram"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D004221"}]},{"id":"13127","type":"Disease","text":["optic and peripheral neuropathy"],"offsets":[[29,60]],"normalized":[{"db_name":"MESH","db_id":"D009901"},{"db_name":"MESH","db_id":"D010523"}]},{"id":"13128","type":"Disease","text":["optic","neuropathy"],"offsets":[[29,34],[50,60]],"normalized":[{"db_name":"MESH","db_id":"D009901"}]},{"id":"13129","type":"Disease","text":["peripheral neuropathy"],"offsets":[[39,60]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"13130","type":"Disease","text":["optic and peripheral neuropathy"],"offsets":[[102,133]],"normalized":[{"db_name":"MESH","db_id":"D009901"},{"db_name":"MESH","db_id":"D010523"}]},{"id":"13131","type":"Disease","text":["optic","neuropathy"],"offsets":[[102,107],[123,133]],"normalized":[{"db_name":"MESH","db_id":"D009901"}]},{"id":"13132","type":"Disease","text":["peripheral neuropathy"],"offsets":[[112,133]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"13133","type":"Chemical","text":["disulfiram"],"offsets":[[155,165]],"normalized":[{"db_name":"MESH","db_id":"D004221"}]},{"id":"13134","type":"Disease","text":["alcohol dependence"],"offsets":[[170,188]],"normalized":[{"db_name":"MESH","db_id":"D000437"}]},{"id":"13135","type":"Disease","text":["loss of vision"],"offsets":[[290,304]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"13136","type":"Disease","text":["headaches"],"offsets":[[336,345]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"13137","type":"Disease","text":["paraesthesia"],"offsets":[[382,394]],"normalized":[{"db_name":"MESH","db_id":"D010292"}]},{"id":"13138","type":"Disease","text":["numbness"],"offsets":[[400,408]],"normalized":[{"db_name":"MESH","db_id":"D006987"}]},{"id":"13139","type":"Disease","text":["scotomata"],"offsets":[[609,618]],"normalized":[{"db_name":"MESH","db_id":"D012607"}]},{"id":"13140","type":"Chemical","text":["disulfiram"],"offsets":[[639,649]],"normalized":[{"db_name":"MESH","db_id":"D004221"}]},{"id":"13141","type":"Disease","text":["alcohol 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{"id":"13174","document_id":"16960342","passages":[{"id":"13175","type":"title","text":["Sustained clinical improvement of a patient with decompensated hepatitis B virus-related cirrhosis after treatment with lamivudine monotherapy."],"offsets":[[0,143]]},{"id":"13176","type":"abstract","text":["Hepatitis B virus (HBV) infection, which causes liver cirrhosis and hepatocellular carcinoma, remains a major health problem in Asian countries. Recent development of vaccine for prevention is reported to be successful in reducing the size of chronically infected carriers, although the standard medical therapies have not been established up to now. In this report, we encountered a patient with decompensated HBV-related cirrhosis who exhibited the dramatic improvements after antiviral therapy. The patient was a 50-year-old woman. Previous conventional medical treatments were not effective for this patient, thus this patient had been referred to our hospital. However, the administration of lamivudine, a reverse transcriptase inhibitor, for 23 months dramatically improved her liver severity. During this period, no drug resistant mutant HBV emerged, and the serum HBV-DNA level was continuously suppressed. These virological responses were also maintained even after the antiviral therapy was discontinued. Moreover, both hepatitis B surface antigen and e antigen were observed to have disappeared in this patient. The administration of lamivudine to patients with HBV-related cirrhosis, like our present case, should be considered as an initial medical therapeutic option, especially in countries where liver transplantation is not reliably available."],"offsets":[[144,1504]]}],"entities":[{"id":"13177","type":"Disease","text":["hepatitis B"],"offsets":[[63,74]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"13178","type":"Disease","text":["cirrhosis"],"offsets":[[89,98]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"13179","type":"Chemical","text":["lamivudine"],"offsets":[[120,130]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"13180","type":"Disease","text":["Hepatitis B virus (HBV) infection"],"offsets":[[144,177]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"13181","type":"Disease","text":["liver cirrhosis"],"offsets":[[192,207]],"normalized":[{"db_name":"MESH","db_id":"D008103"}]},{"id":"13182","type":"Disease","text":["hepatocellular carcinoma"],"offsets":[[212,236]],"normalized":[{"db_name":"MESH","db_id":"D006528"}]},{"id":"13183","type":"Disease","text":["cirrhosis"],"offsets":[[567,576]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"13184","type":"Chemical","text":["lamivudine"],"offsets":[[841,851]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"13185","type":"Chemical","text":["hepatitis B surface antigen and e antigen"],"offsets":[[1174,1215]],"normalized":[{"db_name":"MESH","db_id":"D006514"},{"db_name":"MESH","db_id":"D006513"}]},{"id":"13186","type":"Chemical","text":["hepatitis B surface antigen"],"offsets":[[1174,1201]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"13187","type":"Chemical","text":["hepatitis B","e antigen"],"offsets":[[1174,1185],[1206,1215]],"normalized":[{"db_name":"MESH","db_id":"D006513"}]},{"id":"13188","type":"Chemical","text":["lamivudine"],"offsets":[[1289,1299]],"normalized":[{"db_name":"MESH","db_id":"D019259"}]},{"id":"13189","type":"Disease","text":["cirrhosis"],"offsets":[[1329,1338]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]}],"events":[],"coreferences":[],"relations":[{"id":"13190","type":"CID","arg1_id":"13185","arg2_id":"13177","normalized":[]},{"id":"13191","type":"CID","arg1_id":"13185","arg2_id":"13180","normalized":[]},{"id":"13192","type":"CID","arg1_id":"13186","arg2_id":"13177","normalized":[]},{"id":"13193","type":"CID","arg1_id":"13186","arg2_id":"13180","normalized":[]},{"id":"13194","type":"CID","arg1_id":"13185","arg2_id":"13177","normalized":[]},{"id":"13195","type":"CID","arg1_id":"13185","arg2_id":"13180","normalized":[]},{"id":"13196","type":"CID","arg1_id":"13187","arg2_id":"13177","normalized":[]},{"id":"13197","type":"CID","arg1_id":"13187","arg2_id":"13180","normalized":[]}]}
{"id":"13198","document_id":"11226639","passages":[{"id":"13199","type":"title","text":["Dual effects of melatonin on barbiturate-induced narcosis in rats."],"offsets":[[0,66]]},{"id":"13200","type":"abstract","text":["Melatonin affects the circadian sleep\/wake cycle, but it is not clear whether it may influence drug-induced narcosis. Sodium thiopenthal was administered intraperitoneally into male rats pre-treated with melatonin (0.05, 0.5, 5 and 50 mg\/kg). Melatonin pre-treatment affected in a dual manner barbiturate narcosis, however, no dose-effect correlation was found. In particular, low doses reduced the latency to and prolonged the duration of barbiturate narcosis. In contrast, the highest dose of melatonin (50 mg\/kg) caused a paradoxical increase in the latency and produced a sustained reduction of the duration of narcosis, and a reduction in mortality rate. Melatonin 0.5 and 5 mg\/kg influenced the duration but not the latency of ketamine- or diazepam-induced narcosis. Thus, the dual action of melatonin on pharmacological narcosis seems to be specific for the barbiturate mechanism of action."],"offsets":[[67,964]]}],"entities":[{"id":"13201","type":"Chemical","text":["melatonin"],"offsets":[[16,25]],"normalized":[{"db_name":"MESH","db_id":"D008550"}]},{"id":"13202","type":"Chemical","text":["barbiturate"],"offsets":[[29,40]],"normalized":[{"db_name":"MESH","db_id":"C032232"}]},{"id":"13203","type":"Disease","text":["narcosis"],"offsets":[[49,57]],"normalized":[{"db_name":"MESH","db_id":"D053608"}]},{"id":"13204","type":"Chemical","text":["Melatonin"],"offsets":[[67,76]],"normalized":[{"db_name":"MESH","db_id":"D008550"}]},{"id":"13205","type":"Disease","text":["narcosis"],"offsets":[[175,183]],"normalized":[{"db_name":"MESH","db_id":"D053608"}]},{"id":"13206","type":"Chemical","text":["Sodium 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The three compounds at 1 and 3 mg\/kg p.o. did not significantly decrease spontaneous movement by rats. These findings suggest that NIK-247 at a low dose (0.1-1 mg\/kg p.o.) improves scopolamine-induced amnesia but does not affect spontaneous movement. The findings suggest that NIK-247 may be a useful drug for the treatment of Alzheimer's 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{"id":"13385","document_id":"8766220","passages":[{"id":"13386","type":"title","text":["Nightmares and hallucinations after long-term intake of tramadol combined with antidepressants."],"offsets":[[0,95]]},{"id":"13387","type":"abstract","text":["Tramadol is a weak opioid with effects on adrenergic and serotonergic neurotransmission that is used to treat cancer pain and chronic non malignant pain. This drug was initiated in association with paroxetine and dosulepine hydrochloride in a tetraparetic patient with chronic pain. Fifty-six days after initiation of the treatment the patient presented hallucinations that only stopped after the withdrawal of psycho-active drugs and tramadol. The case report questions the long term use of pain killers combined with psycho-active drugs in chronic non malignant pain, especially if pain is under control."],"offsets":[[96,702]]}],"entities":[{"id":"13388","type":"Disease","text":["hallucinations"],"offsets":[[15,29]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"13389","type":"Chemical","text":["tramadol"],"offsets":[[56,64]],"normalized":[{"db_name":"MESH","db_id":"D014147"}]},{"id":"13390","type":"Chemical","text":["Tramadol"],"offsets":[[96,104]],"normalized":[{"db_name":"MESH","db_id":"D014147"}]},{"id":"13391","type":"Disease","text":["cancer"],"offsets":[[206,212]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"13392","type":"Disease","text":["pain"],"offsets":[[213,217]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"13393","type":"Disease","text":["pain"],"offsets":[[244,248]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"13394","type":"Chemical","text":["paroxetine"],"offsets":[[294,304]],"normalized":[{"db_name":"MESH","db_id":"D017374"}]},{"id":"13395","type":"Chemical","text":["dosulepine hydrochloride"],"offsets":[[309,333]],"normalized":[{"db_name":"MESH","db_id":"D004308"}]},{"id":"13396","type":"Disease","text":["tetraparetic"],"offsets":[[339,351]],"normalized":[]},{"id":"13397","type":"Disease","text":["chronic pain"],"offsets":[[365,377]],"normalized":[{"db_name":"MESH","db_id":"D059350"}]},{"id":"13398","type":"Disease","text":["hallucinations"],"offsets":[[450,464]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"13399","type":"Chemical","text":["tramadol"],"offsets":[[531,539]],"normalized":[{"db_name":"MESH","db_id":"D014147"}]},{"id":"13400","type":"Disease","text":["pain"],"offsets":[[588,592]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"13401","type":"Disease","text":["pain"],"offsets":[[660,664]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"13402","type":"Disease","text":["pain"],"offsets":[[680,684]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]}],"events":[],"coreferences":[],"relations":[{"id":"13403","type":"CID","arg1_id":"13394","arg2_id":"13388","normalized":[]},{"id":"13404","type":"CID","arg1_id":"13394","arg2_id":"13398","normalized":[]},{"id":"13405","type":"CID","arg1_id":"13389","arg2_id":"13388","normalized":[]},{"id":"13406","type":"CID","arg1_id":"13389","arg2_id":"13398","normalized":[]},{"id":"13407","type":"CID","arg1_id":"13390","arg2_id":"13388","normalized":[]},{"id":"13408","type":"CID","arg1_id":"13390","arg2_id":"13398","normalized":[]},{"id":"13409","type":"CID","arg1_id":"13399","arg2_id":"13388","normalized":[]},{"id":"13410","type":"CID","arg1_id":"13399","arg2_id":"13398","normalized":[]},{"id":"13411","type":"CID","arg1_id":"13395","arg2_id":"13388","normalized":[]},{"id":"13412","type":"CID","arg1_id":"13395","arg2_id":"13398","normalized":[]}]}
{"id":"13413","document_id":"8441146","passages":[{"id":"13414","type":"title","text":["Apparent cure of rheumatoid arthritis by bone marrow transplantation."],"offsets":[[0,69]]},{"id":"13415","type":"abstract","text":["We describe the induction of sustained remissions and possible cure of severe erosive rheumatoid arthritis (RA) by bone marrow transplantation (BMT) in 2 patients. BMT was used to treat severe aplastic anemia which was caused by gold in one case and D-penicillamine in the other. In the 8 and 6 years since the transplants (representing 8 and 4 years since cessation of all immunosuppressive therapy, respectively), the RA in each case has been completely quiescent. Although short term remission of severe RA following BMT has been reported, these are the first cases for which prolonged followup has been available. This experience raises the question of the role of BMT itself as a therapeutic option for patients with uncontrolled destructive synovitis."],"offsets":[[70,827]]}],"entities":[{"id":"13416","type":"Disease","text":["rheumatoid arthritis"],"offsets":[[17,37]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"13417","type":"Disease","text":["rheumatoid arthritis"],"offsets":[[156,176]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"13418","type":"Disease","text":["RA"],"offsets":[[178,180]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"13419","type":"Disease","text":["aplastic anemia"],"offsets":[[263,278]],"normalized":[{"db_name":"MESH","db_id":"D000741"}]},{"id":"13420","type":"Chemical","text":["gold"],"offsets":[[299,303]],"normalized":[{"db_name":"MESH","db_id":"D006046"}]},{"id":"13421","type":"Chemical","text":["D-penicillamine"],"offsets":[[320,335]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"13422","type":"Disease","text":["RA"],"offsets":[[490,492]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"13423","type":"Disease","text":["RA"],"offsets":[[577,579]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"13424","type":"Disease","text":["synovitis"],"offsets":[[817,826]],"normalized":[{"db_name":"MESH","db_id":"D013585"}]}],"events":[],"coreferences":[],"relations":[{"id":"13425","type":"CID","arg1_id":"13420","arg2_id":"13419","normalized":[]},{"id":"13426","type":"CID","arg1_id":"13421","arg2_id":"13419","normalized":[]}]}
{"id":"13427","document_id":"3653576","passages":[{"id":"13428","type":"title","text":["Urinary enzymes and protein patterns as indicators of injury to different regions of the kidney."],"offsets":[[0,96]]},{"id":"13429","type":"abstract","text":["Acute experimental models of renal damage to the proximal tubular, glomerular, and papillary regions of the rat were produced by administration of hexachloro-1:3-butadiene (HCBD), puromycin aminonucleoside (PAN), and 2-bromoethylamine (BEA), respectively. Several routine indicators of nephrotoxicity, the enzymes alkaline phosphatase and N-acetyl-beta-glucosaminidase, and the molecular weight of protein excretion were determined on urine samples. Tubular damage produced by HCBD or BEA was discriminated both quantitatively and qualitatively from glomerular damage produced by PAN. The latter was characterized by a pronounced increase in protein excretion, especially proteins with molecular weight greater than 40,000 Da. In contrast, protein excretion in tubular damage was raised only slightly and characterized by excretion of proteins of a wide range of molecular weights. Proximal tubular damage caused by HCBD and papillary damage caused by BEA were distinguished both by conventional urinalysis (volume and specific gravity) and by measurement of the two urinary enzymes. Alkaline phosphatase and glucose were markedly and transiently elevated in proximal tubular damage and N-acetyl-beta-glucosaminidase showed a sustained elevation in papillary damage. It is concluded that both selective urinary enzymes and the molecular weight pattern of urinary proteins can be used to provide diagnostic information about the possible site of renal damage."],"offsets":[[97,1555]]}],"entities":[{"id":"13430","type":"Disease","text":["injury to different regions of the kidney"],"offsets":[[54,95]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"13431","type":"Disease","text":["Acute experimental models of renal damage"],"offsets":[[97,138]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"13432","type":"Chemical","text":["hexachloro-1:3-butadiene"],"offsets":[[244,268]],"normalized":[{"db_name":"MESH","db_id":"C001335"}]},{"id":"13433","type":"Chemical","text":["HCBD"],"offsets":[[270,274]],"normalized":[{"db_name":"MESH","db_id":"C001335"}]},{"id":"13434","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[277,302]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"13435","type":"Chemical","text":["PAN"],"offsets":[[304,307]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"13436","type":"Chemical","text":["2-bromoethylamine"],"offsets":[[314,331]],"normalized":[{"db_name":"MESH","db_id":"C004504"}]},{"id":"13437","type":"Chemical","text":["BEA"],"offsets":[[333,336]],"normalized":[{"db_name":"MESH","db_id":"C004504"}]},{"id":"13438","type":"Disease","text":["nephrotoxicity"],"offsets":[[383,397]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"13439","type":"Disease","text":["protein excretion"],"offsets":[[495,512]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"13440","type":"Chemical","text":["HCBD"],"offsets":[[574,578]],"normalized":[{"db_name":"MESH","db_id":"C001335"}]},{"id":"13441","type":"Chemical","text":["BEA"],"offsets":[[582,585]],"normalized":[{"db_name":"MESH","db_id":"C004504"}]},{"id":"13442","type":"Disease","text":["glomerular damage"],"offsets":[[647,664]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"13443","type":"Chemical","text":["PAN"],"offsets":[[677,680]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"13444","type":"Disease","text":["protein excretion"],"offsets":[[739,756]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"13445","type":"Disease","text":["protein excretion"],"offsets":[[837,854]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"13446","type":"Disease","text":["excretion of proteins"],"offsets":[[919,940]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"13447","type":"Chemical","text":["HCBD"],"offsets":[[1013,1017]],"normalized":[{"db_name":"MESH","db_id":"C001335"}]},{"id":"13448","type":"Chemical","text":["BEA"],"offsets":[[1049,1052]],"normalized":[{"db_name":"MESH","db_id":"C004504"}]},{"id":"13449","type":"Chemical","text":["glucose"],"offsets":[[1206,1213]],"normalized":[{"db_name":"MESH","db_id":"D005947"}]},{"id":"13450","type":"Disease","text":["renal damage"],"offsets":[[1542,1554]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"13451","type":"CID","arg1_id":"13434","arg2_id":"13431","normalized":[]},{"id":"13452","type":"CID","arg1_id":"13435","arg2_id":"13431","normalized":[]},{"id":"13453","type":"CID","arg1_id":"13443","arg2_id":"13431","normalized":[]},{"id":"13454","type":"CID","arg1_id":"13434","arg2_id":"13439","normalized":[]},{"id":"13455","type":"CID","arg1_id":"13434","arg2_id":"13444","normalized":[]},{"id":"13456","type":"CID","arg1_id":"13434","arg2_id":"13445","normalized":[]},{"id":"13457","type":"CID","arg1_id":"13434","arg2_id":"13446","normalized":[]},{"id":"13458","type":"CID","arg1_id":"13435","arg2_id":"13439","normalized":[]},{"id":"13459","type":"CID","arg1_id":"13435","arg2_id":"13444","normalized":[]},{"id":"13460","type":"CID","arg1_id":"13435","arg2_id":"13445","normalized":[]},{"id":"13461","type":"CID","arg1_id":"13435","arg2_id":"13446","normalized":[]},{"id":"13462","type":"CID","arg1_id":"13443","arg2_id":"13439","normalized":[]},{"id":"13463","type":"CID","arg1_id":"13443","arg2_id":"13444","normalized":[]},{"id":"13464","type":"CID","arg1_id":"13443","arg2_id":"13445","normalized":[]},{"id":"13465","type":"CID","arg1_id":"13443","arg2_id":"13446","normalized":[]},{"id":"13466","type":"CID","arg1_id":"13436","arg2_id":"13431","normalized":[]},{"id":"13467","type":"CID","arg1_id":"13437","arg2_id":"13431","normalized":[]},{"id":"13468","type":"CID","arg1_id":"13441","arg2_id":"13431","normalized":[]},{"id":"13469","type":"CID","arg1_id":"13448","arg2_id":"13431","normalized":[]},{"id":"13470","type":"CID","arg1_id":"13432","arg2_id":"13431","normalized":[]},{"id":"13471","type":"CID","arg1_id":"13433","arg2_id":"13431","normalized":[]},{"id":"13472","type":"CID","arg1_id":"13440","arg2_id":"13431","normalized":[]},{"id":"13473","type":"CID","arg1_id":"13447","arg2_id":"13431","normalized":[]}]}
{"id":"13474","document_id":"2750819","passages":[{"id":"13475","type":"title","text":["Neuromuscular blockade with magnesium sulfate and nifedipine."],"offsets":[[0,61]]},{"id":"13476","type":"abstract","text":["A patient who received tocolysis with nifedipine developed neuromuscular blockade after 500 mg of magnesium sulfate was administered. This reaction demonstrates that nifedipine can seriously potentiate the toxicity of magnesium. Caution should be exercised when these two tocolytics are combined."],"offsets":[[62,358]]}],"entities":[{"id":"13477","type":"Disease","text":["Neuromuscular blockade"],"offsets":[[0,22]],"normalized":[{"db_name":"MESH","db_id":"D020879"}]},{"id":"13478","type":"Chemical","text":["magnesium sulfate"],"offsets":[[28,45]],"normalized":[{"db_name":"MESH","db_id":"D008278"}]},{"id":"13479","type":"Chemical","text":["nifedipine"],"offsets":[[50,60]],"normalized":[{"db_name":"MESH","db_id":"D009543"}]},{"id":"13480","type":"Chemical","text":["nifedipine"],"offsets":[[100,110]],"normalized":[{"db_name":"MESH","db_id":"D009543"}]},{"id":"13481","type":"Disease","text":["neuromuscular blockade"],"offsets":[[121,143]],"normalized":[{"db_name":"MESH","db_id":"D020879"}]},{"id":"13482","type":"Chemical","text":["magnesium sulfate"],"offsets":[[160,177]],"normalized":[{"db_name":"MESH","db_id":"D008278"}]},{"id":"13483","type":"Chemical","text":["nifedipine"],"offsets":[[228,238]],"normalized":[{"db_name":"MESH","db_id":"D009543"}]},{"id":"13484","type":"Disease","text":["toxicity"],"offsets":[[268,276]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"13485","type":"Chemical","text":["magnesium"],"offsets":[[280,289]],"normalized":[{"db_name":"MESH","db_id":"D008274"}]}],"events":[],"coreferences":[],"relations":[{"id":"13486","type":"CID","arg1_id":"13478","arg2_id":"13477","normalized":[]},{"id":"13487","type":"CID","arg1_id":"13478","arg2_id":"13481","normalized":[]},{"id":"13488","type":"CID","arg1_id":"13482","arg2_id":"13477","normalized":[]},{"id":"13489","type":"CID","arg1_id":"13482","arg2_id":"13481","normalized":[]},{"id":"13490","type":"CID","arg1_id":"13479","arg2_id":"13477","normalized":[]},{"id":"13491","type":"CID","arg1_id":"13479","arg2_id":"13481","normalized":[]},{"id":"13492","type":"CID","arg1_id":"13480","arg2_id":"13477","normalized":[]},{"id":"13493","type":"CID","arg1_id":"13480","arg2_id":"13481","normalized":[]},{"id":"13494","type":"CID","arg1_id":"13483","arg2_id":"13477","normalized":[]},{"id":"13495","type":"CID","arg1_id":"13483","arg2_id":"13481","normalized":[]}]}
{"id":"13496","document_id":"1899352","passages":[{"id":"13497","type":"title","text":["Ifosfamide continuous infusion without mesna. A phase I trial of a 14-day cycle."],"offsets":[[0,80]]},{"id":"13498","type":"abstract","text":["Twenty patients received 27 courses of ifosfamide administered as a 24-hour continuous infusion for 14 days without Mesna. The goal of the study was to deliver a dose rate and total cumulative dose of ifosfamide that would be comparable to standard bolus or short-term infusions administered with Mesna. Dose escalations proceeded from 200 to 300, 400, 450, 500, and 550 mg\/m2\/d. Four patients developed transient microscopic hematuria at 400, 450, and 500 mg\/m2\/d. There were no instances of macroscopic hematuria. At 550 mg\/m2\/d, three patients experienced nonurologic toxicity; confusion (1), nausea (1), and Grade 2 leukopenia (1). The recommended dose of 500 mg\/m2\/d delivers a total dose of 7 g\/m2 per cycle, which is comparable to that delivered in clinical practice for bolus or short-term infusion. Because few patients received multiple courses over time, the cumulative effects are indeterminate in the present trial. The frequency and predictability of hematuria are not precise, and at least daily monitoring by urine Hematest is essential, adding Mesna to the infusate in patients with persistent hematuria. The protracted infusion schedule for ifosfamide permits convenient outpatient administration without Mesna and reduces the drug cost of clinical usage of this agent by up to  890 per cycle. Clinical activity was demonstrated in a single patient, but a comparative trial of standard bolus schedules with the protracted infusion schedule will be necessary to determine if the clinical effectiveness of the drug is maintained."],"offsets":[[81,1626]]}],"entities":[{"id":"13499","type":"Chemical","text":["Ifosfamide"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"13500","type":"Chemical","text":["mesna"],"offsets":[[39,44]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"13501","type":"Chemical","text":["ifosfamide"],"offsets":[[120,130]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"13502","type":"Chemical","text":["Mesna"],"offsets":[[197,202]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"13503","type":"Chemical","text":["ifosfamide"],"offsets":[[282,292]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"13504","type":"Chemical","text":["Mesna"],"offsets":[[378,383]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"13505","type":"Disease","text":["hematuria"],"offsets":[[507,516]],"normalized":[{"db_name":"MESH","db_id":"D006417"}]},{"id":"13506","type":"Disease","text":["hematuria"],"offsets":[[586,595]],"normalized":[{"db_name":"MESH","db_id":"D006417"}]},{"id":"13507","type":"Disease","text":["toxicity"],"offsets":[[652,660]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"13508","type":"Disease","text":["confusion"],"offsets":[[662,671]],"normalized":[{"db_name":"MESH","db_id":"D003221"}]},{"id":"13509","type":"Disease","text":["nausea"],"offsets":[[677,683]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"13510","type":"Disease","text":["leukopenia"],"offsets":[[701,711]],"normalized":[{"db_name":"MESH","db_id":"D007970"}]},{"id":"13511","type":"Disease","text":["hematuria"],"offsets":[[1046,1055]],"normalized":[{"db_name":"MESH","db_id":"D006417"}]},{"id":"13512","type":"Chemical","text":["Mesna"],"offsets":[[1142,1147]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"13513","type":"Disease","text":["hematuria"],"offsets":[[1192,1201]],"normalized":[{"db_name":"MESH","db_id":"D006417"}]},{"id":"13514","type":"Chemical","text":["ifosfamide"],"offsets":[[1240,1250]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"13515","type":"Chemical","text":["Mesna"],"offsets":[[1304,1309]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]}],"events":[],"coreferences":[],"relations":[{"id":"13516","type":"CID","arg1_id":"13499","arg2_id":"13505","normalized":[]},{"id":"13517","type":"CID","arg1_id":"13499","arg2_id":"13506","normalized":[]},{"id":"13518","type":"CID","arg1_id":"13499","arg2_id":"13511","normalized":[]},{"id":"13519","type":"CID","arg1_id":"13499","arg2_id":"13513","normalized":[]},{"id":"13520","type":"CID","arg1_id":"13501","arg2_id":"13505","normalized":[]},{"id":"13521","type":"CID","arg1_id":"13501","arg2_id":"13506","normalized":[]},{"id":"13522","type":"CID","arg1_id":"13501","arg2_id":"13511","normalized":[]},{"id":"13523","type":"CID","arg1_id":"13501","arg2_id":"13513","normalized":[]},{"id":"13524","type":"CID","arg1_id":"13503","arg2_id":"13505","normalized":[]},{"id":"13525","type":"CID","arg1_id":"13503","arg2_id":"13506","normalized":[]},{"id":"13526","type":"CID","arg1_id":"13503","arg2_id":"13511","normalized":[]},{"id":"13527","type":"CID","arg1_id":"13503","arg2_id":"13513","normalized":[]},{"id":"13528","type":"CID","arg1_id":"13514","arg2_id":"13505","normalized":[]},{"id":"13529","type":"CID","arg1_id":"13514","arg2_id":"13506","normalized":[]},{"id":"13530","type":"CID","arg1_id":"13514","arg2_id":"13511","normalized":[]},{"id":"13531","type":"CID","arg1_id":"13514","arg2_id":"13513","normalized":[]},{"id":"13532","type":"CID","arg1_id":"13499","arg2_id":"13510","normalized":[]},{"id":"13533","type":"CID","arg1_id":"13501","arg2_id":"13510","normalized":[]},{"id":"13534","type":"CID","arg1_id":"13503","arg2_id":"13510","normalized":[]},{"id":"13535","type":"CID","arg1_id":"13514","arg2_id":"13510","normalized":[]},{"id":"13536","type":"CID","arg1_id":"13499","arg2_id":"13508","normalized":[]},{"id":"13537","type":"CID","arg1_id":"13501","arg2_id":"13508","normalized":[]},{"id":"13538","type":"CID","arg1_id":"13503","arg2_id":"13508","normalized":[]},{"id":"13539","type":"CID","arg1_id":"13514","arg2_id":"13508","normalized":[]},{"id":"13540","type":"CID","arg1_id":"13499","arg2_id":"13509","normalized":[]},{"id":"13541","type":"CID","arg1_id":"13501","arg2_id":"13509","normalized":[]},{"id":"13542","type":"CID","arg1_id":"13503","arg2_id":"13509","normalized":[]},{"id":"13543","type":"CID","arg1_id":"13514","arg2_id":"13509","normalized":[]}]}
{"id":"13544","document_id":"18161408","passages":[{"id":"13545","type":"title","text":["Myocardial infarction in pregnancy associated with clomiphene citrate for ovulation induction: a case report."],"offsets":[[0,109]]},{"id":"13546","type":"abstract","text":["BACKGROUND: Clomiphene citrate (CC) is commonly prescribed for ovulation induction. It is considered safe, with minimal side effects. Thromboembolism is a rare but life-threatening complication that has been reported after ovulation induction with CC. Spontaneous coronary thrombosis or thromboembolism with subsequent clot lysis has been suggested as one of the most common causes of myocardial infarction (MI) during pregnancy, with a subsequently normal coronary angiogram. CASE: A 33-year-old woman with a 5-week gestation had recently received CC for ovulation induction and presented with chest pain. An electrocardiogram showed a lateral and anterior wall myocardial infarction. Cardiac enzymes showed a peak rise in troponin I to 9.10 ng\/mL. An initial exercise stress test was normal. At the time of admission, the patient was at high risk of radiation injury to the fetus, so a coronary angiogram was postponed until the second trimester. It showed normal coronary vessels. CONCLUSION: This appears to be the first reported case documenting a possible association between CC and myocardial infarction. Thrombosis might be a rare but hazardous complication of CC. Given this life-threatening complication, appropriate prophylactic measures should be used in high-risk woman undergoing ovarian stimulation."],"offsets":[[110,1424]]}],"entities":[{"id":"13547","type":"Disease","text":["Myocardial infarction"],"offsets":[[0,21]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"13548","type":"Chemical","text":["clomiphene citrate"],"offsets":[[51,69]],"normalized":[{"db_name":"MESH","db_id":"D002996"}]},{"id":"13549","type":"Chemical","text":["Clomiphene citrate"],"offsets":[[122,140]],"normalized":[{"db_name":"MESH","db_id":"D002996"}]},{"id":"13550","type":"Chemical","text":["CC"],"offsets":[[142,144]],"normalized":[{"db_name":"MESH","db_id":"D002996"}]},{"id":"13551","type":"Disease","text":["Thromboembolism"],"offsets":[[244,259]],"normalized":[{"db_name":"MESH","db_id":"D013923"}]},{"id":"13552","type":"Chemical","text":["CC"],"offsets":[[358,360]],"normalized":[{"db_name":"MESH","db_id":"D002996"}]},{"id":"13553","type":"Disease","text":["coronary thrombosis"],"offsets":[[374,393]],"normalized":[{"db_name":"MESH","db_id":"D003328"}]},{"id":"13554","type":"Disease","text":["thromboembolism"],"offsets":[[397,412]],"normalized":[{"db_name":"MESH","db_id":"D013923"}]},{"id":"13555","type":"Disease","text":["myocardial infarction"],"offsets":[[495,516]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"13556","type":"Disease","text":["MI"],"offsets":[[518,520]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"13557","type":"Chemical","text":["CC"],"offsets":[[659,661]],"normalized":[{"db_name":"MESH","db_id":"D002996"}]},{"id":"13558","type":"Disease","text":["chest pain"],"offsets":[[705,715]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"13559","type":"Disease","text":["myocardial infarction"],"offsets":[[773,794]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"13560","type":"Disease","text":["radiation injury"],"offsets":[[962,978]],"normalized":[{"db_name":"MESH","db_id":"D011832"}]},{"id":"13561","type":"Chemical","text":["CC"],"offsets":[[1192,1194]],"normalized":[{"db_name":"MESH","db_id":"D002996"}]},{"id":"13562","type":"Disease","text":["myocardial infarction"],"offsets":[[1199,1220]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"13563","type":"Disease","text":["Thrombosis"],"offsets":[[1222,1232]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]},{"id":"13564","type":"Chemical","text":["CC"],"offsets":[[1279,1281]],"normalized":[{"db_name":"MESH","db_id":"D002996"}]}],"events":[],"coreferences":[],"relations":[{"id":"13565","type":"CID","arg1_id":"13548","arg2_id":"13547","normalized":[]},{"id":"13566","type":"CID","arg1_id":"13548","arg2_id":"13555","normalized":[]},{"id":"13567","type":"CID","arg1_id":"13548","arg2_id":"13556","normalized":[]},{"id":"13568","type":"CID","arg1_id":"13548","arg2_id":"13559","normalized":[]},{"id":"13569","type":"CID","arg1_id":"13548","arg2_id":"13562","normalized":[]},{"id":"13570","type":"CID","arg1_id":"13549","arg2_id":"13547","normalized":[]},{"id":"13571","type":"CID","arg1_id":"13549","arg2_id":"13555","normalized":[]},{"id":"13572","type":"CID","arg1_id":"13549","arg2_id":"13556","normalized":[]},{"id":"13573","type":"CID","arg1_id":"13549","arg2_id":"13559","normalized":[]},{"id":"13574","type":"CID","arg1_id":"13549","arg2_id":"13562","normalized":[]},{"id":"13575","type":"CID","arg1_id":"13550","arg2_id":"13547","normalized":[]},{"id":"13576","type":"CID","arg1_id":"13550","arg2_id":"13555","normalized":[]},{"id":"13577","type":"CID","arg1_id":"13550","arg2_id":"13556","normalized":[]},{"id":"13578","type":"CID","arg1_id":"13550","arg2_id":"13559","normalized":[]},{"id":"13579","type":"CID","arg1_id":"13550","arg2_id":"13562","normalized":[]},{"id":"13580","type":"CID","arg1_id":"13552","arg2_id":"13547","normalized":[]},{"id":"13581","type":"CID","arg1_id":"13552","arg2_id":"13555","normalized":[]},{"id":"13582","type":"CID","arg1_id":"13552","arg2_id":"13556","normalized":[]},{"id":"13583","type":"CID","arg1_id":"13552","arg2_id":"13559","normalized":[]},{"id":"13584","type":"CID","arg1_id":"13552","arg2_id":"13562","normalized":[]},{"id":"13585","type":"CID","arg1_id":"13557","arg2_id":"13547","normalized":[]},{"id":"13586","type":"CID","arg1_id":"13557","arg2_id":"13555","normalized":[]},{"id":"13587","type":"CID","arg1_id":"13557","arg2_id":"13556","normalized":[]},{"id":"13588","type":"CID","arg1_id":"13557","arg2_id":"13559","normalized":[]},{"id":"13589","type":"CID","arg1_id":"13557","arg2_id":"13562","normalized":[]},{"id":"13590","type":"CID","arg1_id":"13561","arg2_id":"13547","normalized":[]},{"id":"13591","type":"CID","arg1_id":"13561","arg2_id":"13555","normalized":[]},{"id":"13592","type":"CID","arg1_id":"13561","arg2_id":"13556","normalized":[]},{"id":"13593","type":"CID","arg1_id":"13561","arg2_id":"13559","normalized":[]},{"id":"13594","type":"CID","arg1_id":"13561","arg2_id":"13562","normalized":[]},{"id":"13595","type":"CID","arg1_id":"13564","arg2_id":"13547","normalized":[]},{"id":"13596","type":"CID","arg1_id":"13564","arg2_id":"13555","normalized":[]},{"id":"13597","type":"CID","arg1_id":"13564","arg2_id":"13556","normalized":[]},{"id":"13598","type":"CID","arg1_id":"13564","arg2_id":"13559","normalized":[]},{"id":"13599","type":"CID","arg1_id":"13564","arg2_id":"13562","normalized":[]},{"id":"13600","type":"CID","arg1_id":"13548","arg2_id":"13551","normalized":[]},{"id":"13601","type":"CID","arg1_id":"13548","arg2_id":"13554","normalized":[]},{"id":"13602","type":"CID","arg1_id":"13549","arg2_id":"13551","normalized":[]},{"id":"13603","type":"CID","arg1_id":"13549","arg2_id":"13554","normalized":[]},{"id":"13604","type":"CID","arg1_id":"13550","arg2_id":"13551","normalized":[]},{"id":"13605","type":"CID","arg1_id":"13550","arg2_id":"13554","normalized":[]},{"id":"13606","type":"CID","arg1_id":"13552","arg2_id":"13551","normalized":[]},{"id":"13607","type":"CID","arg1_id":"13552","arg2_id":"13554","normalized":[]},{"id":"13608","type":"CID","arg1_id":"13557","arg2_id":"13551","normalized":[]},{"id":"13609","type":"CID","arg1_id":"13557","arg2_id":"13554","normalized":[]},{"id":"13610","type":"CID","arg1_id":"13561","arg2_id":"13551","normalized":[]},{"id":"13611","type":"CID","arg1_id":"13561","arg2_id":"13554","normalized":[]},{"id":"13612","type":"CID","arg1_id":"13564","arg2_id":"13551","normalized":[]},{"id":"13613","type":"CID","arg1_id":"13564","arg2_id":"13554","normalized":[]}]}
{"id":"13614","document_id":"17574447","passages":[{"id":"13615","type":"title","text":["Hepatonecrosis and cholangitis related to long-term phenobarbital therapy: an autopsy report of two patients."],"offsets":[[0,109]]},{"id":"13616","type":"abstract","text":["Phenobarbital (PB) has a reputation for safety, and it is commonly believed that PB-related increases in serum aminotransferase levels do not indicate or predict the development of significant chronic liver disease. Here we report of two adult patients with a long history of epilepsy treated with PB who died suddenly: one as consequence of cardiac arrest, the other of acute bronchopneumonia. At autopsy, analysis of liver parenchyma revealed rich portal inflammatory infiltrate, which consisted of mixed eosinophil and monocyte cells, associated with several foci of necrosis surrounded by a hard ring of non-specific granulomatous tissue. Inflammatory reactions of internal and external hepatic biliary ducts were also seen. Our findings illustrate that PB may be associated with chronic liver damage, which may lead to more serious and deleterious consequences. For this reason, each clinician should recognize this entity in the differential diagnosis of PB-related asymptomatic chronic hepatic enzyme dysfunction."],"offsets":[[110,1130]]}],"entities":[{"id":"13617","type":"Disease","text":["Hepatonecrosis"],"offsets":[[0,14]],"normalized":[]},{"id":"13618","type":"Disease","text":["cholangitis"],"offsets":[[19,30]],"normalized":[{"db_name":"MESH","db_id":"D002761"}]},{"id":"13619","type":"Chemical","text":["phenobarbital"],"offsets":[[52,65]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"13620","type":"Chemical","text":["Phenobarbital"],"offsets":[[110,123]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"13621","type":"Chemical","text":["PB"],"offsets":[[125,127]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"13622","type":"Chemical","text":["PB"],"offsets":[[191,193]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"13623","type":"Disease","text":["liver disease"],"offsets":[[311,324]],"normalized":[{"db_name":"MESH","db_id":"D008107"}]},{"id":"13624","type":"Disease","text":["epilepsy"],"offsets":[[386,394]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"13625","type":"Chemical","text":["PB"],"offsets":[[408,410]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"13626","type":"Disease","text":["cardiac arrest"],"offsets":[[452,466]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"13627","type":"Disease","text":["bronchopneumonia"],"offsets":[[487,503]],"normalized":[{"db_name":"MESH","db_id":"D001996"}]},{"id":"13628","type":"Disease","text":["necrosis"],"offsets":[[680,688]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"13629","type":"Chemical","text":["PB"],"offsets":[[868,870]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"13630","type":"Disease","text":["liver damage"],"offsets":[[902,914]],"normalized":[{"db_name":"MESH","db_id":"D008107"}]},{"id":"13631","type":"Chemical","text":["PB"],"offsets":[[1071,1073]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"13632","type":"Disease","text":["chronic hepatic enzyme dysfunction"],"offsets":[[1095,1129]],"normalized":[{"db_name":"MESH","db_id":"D056487"}]}],"events":[],"coreferences":[],"relations":[{"id":"13633","type":"CID","arg1_id":"13619","arg2_id":"13618","normalized":[]},{"id":"13634","type":"CID","arg1_id":"13620","arg2_id":"13618","normalized":[]},{"id":"13635","type":"CID","arg1_id":"13621","arg2_id":"13618","normalized":[]},{"id":"13636","type":"CID","arg1_id":"13622","arg2_id":"13618","normalized":[]},{"id":"13637","type":"CID","arg1_id":"13625","arg2_id":"13618","normalized":[]},{"id":"13638","type":"CID","arg1_id":"13629","arg2_id":"13618","normalized":[]},{"id":"13639","type":"CID","arg1_id":"13631","arg2_id":"13618","normalized":[]},{"id":"13640","type":"CID","arg1_id":"13619","arg2_id":"13623","normalized":[]},{"id":"13641","type":"CID","arg1_id":"13619","arg2_id":"13630","normalized":[]},{"id":"13642","type":"CID","arg1_id":"13620","arg2_id":"13623","normalized":[]},{"id":"13643","type":"CID","arg1_id":"13620","arg2_id":"13630","normalized":[]},{"id":"13644","type":"CID","arg1_id":"13621","arg2_id":"13623","normalized":[]},{"id":"13645","type":"CID","arg1_id":"13621","arg2_id":"13630","normalized":[]},{"id":"13646","type":"CID","arg1_id":"13622","arg2_id":"13623","normalized":[]},{"id":"13647","type":"CID","arg1_id":"13622","arg2_id":"13630","normalized":[]},{"id":"13648","type":"CID","arg1_id":"13625","arg2_id":"13623","normalized":[]},{"id":"13649","type":"CID","arg1_id":"13625","arg2_id":"13630","normalized":[]},{"id":"13650","type":"CID","arg1_id":"13629","arg2_id":"13623","normalized":[]},{"id":"13651","type":"CID","arg1_id":"13629","arg2_id":"13630","normalized":[]},{"id":"13652","type":"CID","arg1_id":"13631","arg2_id":"13623","normalized":[]},{"id":"13653","type":"CID","arg1_id":"13631","arg2_id":"13630","normalized":[]}]}
{"id":"13654","document_id":"16710500","passages":[{"id":"13655","type":"title","text":["Ethambutol-associated optic neuropathy."],"offsets":[[0,39]]},{"id":"13656","type":"abstract","text":["INTRODUCTION: Ethambutol is used in the treatment of tuberculosis, which is still prevalent in Southeast Asia, and can be associated with permanent visual loss. We report 3 cases which presented with bitemporal hemianopia. CLINICAL PICTURE: Three patients with ethambutol-associated toxic optic neuropathy are described. All 3 patients had loss of central visual acuity, colour vision (Ishihara) and visual field. The visual field loss had a bitemporal flavour, suggesting involvement of the optic chiasm. TREATMENT: Despite stopping ethambutol on diagnosis, visual function continued to deteriorate for a few months. Subsequent improvement was mild in 2 cases. In the third case, visual acuity and colour vision normalised but the optic discs were pale. OUTCOME: All 3 patients had some permanent loss of visual function. CONCLUSIONS: Ethambutol usage is associated with permanent visual loss and should be avoided if possible or used with caution and proper ophthalmological follow-up. The author postulates that in cases of ethambutol associated chiasmopathy, ethambutol may initially affect the optic nerves and subsequently progress to involve the optic chiasm."],"offsets":[[40,1206]]}],"entities":[{"id":"13657","type":"Chemical","text":["Ethambutol"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D004977"}]},{"id":"13658","type":"Disease","text":["optic neuropathy"],"offsets":[[22,38]],"normalized":[{"db_name":"MESH","db_id":"D009901"}]},{"id":"13659","type":"Chemical","text":["Ethambutol"],"offsets":[[54,64]],"normalized":[{"db_name":"MESH","db_id":"D004977"}]},{"id":"13660","type":"Disease","text":["tuberculosis"],"offsets":[[93,105]],"normalized":[{"db_name":"MESH","db_id":"D014376"}]},{"id":"13661","type":"Disease","text":["visual loss"],"offsets":[[188,199]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"13662","type":"Disease","text":["bitemporal 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{"id":"13722","document_id":"11694026","passages":[{"id":"13723","type":"title","text":["Tolerability of nimesulide and paracetamol in patients with NSAID-induced urticaria\/angioedema."],"offsets":[[0,95]]},{"id":"13724","type":"abstract","text":["Previous studies evaluated the tolerance of nimesulide and paracetamol in subjects with cutaneous, respiratory and anaphylactoid reactions induced by nonsteroidal anti-inflammatory drugs (NSAIDs). In this study we investigated tolerability and reliability of nimesulide and paracetamol in a very large number of patients with an exclusive well-documented history of NSAID-induced urticaria\/angioedema. Furthermore, we evaluated whether some factors have the potential to increase the risk of reaction to paracetamol and nimesulide. A single-placebo-controlled oral challenge procedure with nimesulide or paracetamol was applied to 829 patients with a history of NSAID-induced urticaria\/angioedema. A total of 75\/829 (9.4%) patients experienced reactions to nimesulide or paracetamol. Of the 715 patients tested with nimesulide 62 (8.6%) showed a positive test, while of 114 subjects submitted to the challenge with paracetamol, 13 (9.6%) did not tolerate this drug. Furthermore, 18.28% of patients with a history of chronic urticaria and 11.8% of subjects with an history of NSAID-induced urticaria\/angioedema or angioedema alone (with or without chronic urticaria) resulted to be intolerant to alternative drugs. Taken together, our results confirm the good tolerability of nimesulide and paracetamol in patients who experienced urticaria\/angioedema caused by NSAIDs. However, the risk of reaction to these alternative study drugs is statistically increased by a history of chronic urticaria and, above all, by a history of NSAID-induced 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{"id":"13932","document_id":"11282081","passages":[{"id":"13933","type":"title","text":["Effects of verapamil on atrial fibrillation and its electrophysiological determinants in dogs."],"offsets":[[0,94]]},{"id":"13934","type":"abstract","text":["BACKGROUND: Atrial tachycardia-induced remodeling promotes the occurrence and maintenance of atrial fibrillation (AF) and decreases L-type Ca(2+) current. There is also a clinical suggestion that acute L-type Ca(2) channel blockade can promote AF, consistent with an AF promoting effect of Ca(2+) channel inhibition. METHODS: To evaluate the potential mechanisms of AF promotion by Ca(2+) channel blockers, we administered verapamil to morphine-chloralose anesthetized dogs. Diltiazem was used as a comparison drug and autonomic blockade with atropine and nadolol was applied in some experiments. Epicardial mapping with 240 epicardial electrodes was used to evaluate activation during AF. RESULTS: Verapamil caused AF promotion in six dogs, increasing mean duration of AF induced by burst pacing, from 8+\/-4 s (mean+\/-S.E.) to 95+\/-39 s (P<0.01 vs. control) at a loading dose of 0.1 mg\/kg and 228+\/-101 s (P<0.0005 vs. control) at a dose of 0.2 mg\/kg. Underlying electrophysiological mechanisms were studied in detail in five additional dogs under control conditions and in the presence of the higher dose of verapamil. In these experiments, verapamil shortened mean effective refractory period (ERP) from 122+\/-5 to 114+\/-4 ms (P<0.02) at a cycle length of 300 ms, decreased ERP heterogeneity (from 15+\/-1 to 10+\/-1%, P<0.05), heterogeneously accelerated atrial conduction and decreased the cycle length of AF (94+\/-4 to 84+\/-3 ms, P<0.005). Diltiazem did not affect ERP, AF cycle length or AF duration, but produced conduction acceleration similar to that caused by verapamil (n=5). In the presence of autonomic blockade, verapamil failed to promote AF and increased, rather than decreasing, refractoriness. Neither verapamil nor diltiazem affected atrial conduction in the presence of autonomic blockade. Epicardial mapping suggested that verapamil promoted AF by increasing the number of simultaneous wavefronts reflected by separate zones of reactivation in each cycle. CONCLUSIONS: Verapamil promotes AF in normal dogs by promoting multiple circuit reentry, an effect dependent on intact autonomic tone and not shared by diltiazem."],"offsets":[[95,2233]]}],"entities":[{"id":"13935","type":"Chemical","text":["verapamil"],"offsets":[[11,20]],"normalized":[{"db_name":"MESH","db_id":"D014700"}]},{"id":"13936","type":"Disease","text":["atrial fibrillation"],"offsets":[[24,43]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"13937","type":"Disease","text":["Atrial tachycardia"],"offsets":[[107,125]],"normalized":[{"db_name":"MESH","db_id":"D013617"}]},{"id":"13938","type":"Disease","text":["atrial 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{"id":"14123","document_id":"10074612","passages":[{"id":"14124","type":"title","text":["Hypotension, bradycardia, and asystole after high-dose intravenous methylprednisolone in a monitored patient."],"offsets":[[0,109]]},{"id":"14125","type":"abstract","text":["We report a case of hypotension, bradycardia, and asystole after intravenous administration of high-dose methylprednisolone in a 73-year-old patient who underwent electrocardiographic (ECG) monitoring throughout the episode. There was a history of ischemic cardiac disease 9 years earlier. The patient was admitted with a pulmonary-renal syndrome with hemoptysis, rapidly progressive renal failure, and hypoxemia that required mechanical ventilation in the intensive care unit. After receiving advanced cardiopulmonary resuscitation, the patient recovered cardiac rhythm. The ECG showed a junctional rhythm without ventricular arrhythmia. This study reviews the current proposed mechanisms of sudden death after a high dose of intravenous methylprednisolone (IVMP). These mechanisms are not well understood because, in most cases, the patients were not monitored at the moment of the event. Rapid infusion and underlying cardiac disease were important risk factors in the case reported here, and the authors discount ventricular arrhythmia as the main mechanism."],"offsets":[[110,1172]]}],"entities":[{"id":"14126","type":"Disease","text":["Hypotension"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"14127","type":"Disease","text":["bradycardia"],"offsets":[[13,24]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"14128","type":"Disease","text":["asystole"],"offsets":[[30,38]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"14129","type":"Chemical","text":["methylprednisolone"],"offsets":[[67,85]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"14130","type":"Disease","text":["hypotension"],"offsets":[[130,141]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"14131","type":"Disease","text":["bradycardia"],"offsets":[[143,154]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"14132","type":"Disease","text":["asystole"],"offsets":[[160,168]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"14133","type":"Chemical","text":["methylprednisolone"],"offsets":[[215,233]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"14134","type":"Disease","text":["ischemic"],"offsets":[[358,366]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"14135","type":"Disease","text":["cardiac disease"],"offsets":[[367,382]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"14136","type":"Disease","text":["pulmonary-renal syndrome"],"offsets":[[432,456]],"normalized":[{"db_name":"MESH","db_id":"C538458"}]},{"id":"14137","type":"Disease","text":["hemoptysis"],"offsets":[[462,472]],"normalized":[{"db_name":"MESH","db_id":"D006469"}]},{"id":"14138","type":"Disease","text":["renal failure"],"offsets":[[494,507]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"14139","type":"Disease","text":["hypoxemia"],"offsets":[[513,522]],"normalized":[{"db_name":"MESH","db_id":"D000860"}]},{"id":"14140","type":"Disease","text":["ventricular arrhythmia"],"offsets":[[725,747]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"14141","type":"Disease","text":["sudden death"],"offsets":[[803,815]],"normalized":[{"db_name":"MESH","db_id":"D003645"}]},{"id":"14142","type":"Chemical","text":["methylprednisolone"],"offsets":[[849,867]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"14143","type":"Chemical","text":["IVMP"],"offsets":[[869,873]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"14144","type":"Disease","text":["cardiac disease"],"offsets":[[1031,1046]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"14145","type":"Disease","text":["ventricular arrhythmia"],"offsets":[[1127,1149]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]}],"events":[],"coreferences":[],"relations":[{"id":"14146","type":"CID","arg1_id":"14129","arg2_id":"14127","normalized":[]},{"id":"14147","type":"CID","arg1_id":"14129","arg2_id":"14131","normalized":[]},{"id":"14148","type":"CID","arg1_id":"14133","arg2_id":"14127","normalized":[]},{"id":"14149","type":"CID","arg1_id":"14133","arg2_id":"14131","normalized":[]},{"id":"14150","type":"CID","arg1_id":"14142","arg2_id":"14127","normalized":[]},{"id":"14151","type":"CID","arg1_id":"14142","arg2_id":"14131","normalized":[]},{"id":"14152","type":"CID","arg1_id":"14143","arg2_id":"14127","normalized":[]},{"id":"14153","type":"CID","arg1_id":"14143","arg2_id":"14131","normalized":[]},{"id":"14154","type":"CID","arg1_id":"14129","arg2_id":"14128","normalized":[]},{"id":"14155","type":"CID","arg1_id":"14129","arg2_id":"14132","normalized":[]},{"id":"14156","type":"CID","arg1_id":"14133","arg2_id":"14128","normalized":[]},{"id":"14157","type":"CID","arg1_id":"14133","arg2_id":"14132","normalized":[]},{"id":"14158","type":"CID","arg1_id":"14142","arg2_id":"14128","normalized":[]},{"id":"14159","type":"CID","arg1_id":"14142","arg2_id":"14132","normalized":[]},{"id":"14160","type":"CID","arg1_id":"14143","arg2_id":"14128","normalized":[]},{"id":"14161","type":"CID","arg1_id":"14143","arg2_id":"14132","normalized":[]},{"id":"14162","type":"CID","arg1_id":"14129","arg2_id":"14126","normalized":[]},{"id":"14163","type":"CID","arg1_id":"14129","arg2_id":"14130","normalized":[]},{"id":"14164","type":"CID","arg1_id":"14133","arg2_id":"14126","normalized":[]},{"id":"14165","type":"CID","arg1_id":"14133","arg2_id":"14130","normalized":[]},{"id":"14166","type":"CID","arg1_id":"14142","arg2_id":"14126","normalized":[]},{"id":"14167","type":"CID","arg1_id":"14142","arg2_id":"14130","normalized":[]},{"id":"14168","type":"CID","arg1_id":"14143","arg2_id":"14126","normalized":[]},{"id":"14169","type":"CID","arg1_id":"14143","arg2_id":"14130","normalized":[]}]}
{"id":"14170","document_id":"9209318","passages":[{"id":"14171","type":"title","text":["Lifetime treatment of mice with azidothymidine (AZT) produces myelodysplasia."],"offsets":[[0,77]]},{"id":"14172","type":"abstract","text":["AZT has induced a macrocytic anemia in AIDS patients on long term AZT therapy. It is generally assumed that DNA elongation is stopped by the insertion of AZT into the chain in place of thymidine thus preventing the phosphate hydroxyl linkages and therefore suppresses hemopoietic progenitor cell proliferation in an early stage of differentiation. CBA\/Ca male mice started on AZT 0.75 mg\/ml H2O at 84 days of age and kept on it for 687 days when dosage reduced to 0.5 mg\/ml H2O for a group, another group removed from AZT to see recovery, and third group remained on 0.75 mg. At 687 days mice that had been on 0.75 mg had average platelet counts of 2.5 x 10(6). Histological examination on 9 of 10 mice with such thrombocytopenia showed changes compatible with myelodysplastic syndrome (MDS). A variety of histological patterns was observed. There were two cases of hypocellular myelodysplasia, two cases of hypersegmented myelodysplastic granulocytosis, two cases of hypercellular marrow with abnormal megakaryocytes with bizarre nuclei, one case of megakaryocytic myelosis associated with a hyperplastic marrow, dysmyelopoiesis and a hypocellular marrow and two cases of myelodysplasia with dyserythropoiesis, hemosiderosis and a hypocellular marrow. Above mentioned AZT incorporation may have induced an ineffective hemopoiesis in the primitive hemopoietic progenitor cells, which is known to be seen commonly in the myelodysplastic syndrome."],"offsets":[[78,1523]]}],"entities":[{"id":"14173","type":"Chemical","text":["azidothymidine"],"offsets":[[32,46]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"14174","type":"Chemical","text":["AZT"],"offsets":[[48,51]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"14175","type":"Disease","text":["myelodysplasia"],"offsets":[[62,76]],"normalized":[{"db_name":"MESH","db_id":"D009190"}]},{"id":"14176","type":"Chemical","text":["AZT"],"offsets":[[78,81]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"14177","type":"Disease","text":["macrocytic anemia"],"offsets":[[96,113]],"normalized":[{"db_name":"MESH","db_id":"D000748"}]},{"id":"14178","type":"Disease","text":["AIDS"],"offsets":[[117,121]],"normalized":[{"db_name":"MESH","db_id":"D000163"}]},{"id":"14179","type":"Chemical","text":["AZT"],"offsets":[[144,147]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"14180","type":"Chemical","text":["AZT"],"offsets":[[232,235]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"14181","type":"Chemical","text":["thymidine"],"offsets":[[263,272]],"normalized":[{"db_name":"MESH","db_id":"D013936"}]},{"id":"14182","type":"Chemical","text":["phosphate"],"offsets":[[293,302]],"normalized":[{"db_name":"MESH","db_id":"D010710"}]},{"id":"14183","type":"Chemical","text":["AZT"],"offsets":[[454,457]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"14184","type":"Chemical","text":["AZT"],"offsets":[[596,599]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"14185","type":"Disease","text":["thrombocytopenia"],"offsets":[[791,807]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"14186","type":"Disease","text":["myelodysplastic 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marrow"],"offsets":[[1214,1233]],"normalized":[{"db_name":"MESH","db_id":"D001855"}]},{"id":"14193","type":"Disease","text":["myelodysplasia"],"offsets":[[1251,1265]],"normalized":[{"db_name":"MESH","db_id":"D009190"}]},{"id":"14194","type":"Disease","text":["dyserythropoiesis"],"offsets":[[1271,1288]],"normalized":[]},{"id":"14195","type":"Disease","text":["hemosiderosis"],"offsets":[[1290,1303]],"normalized":[{"db_name":"MESH","db_id":"D006486"}]},{"id":"14196","type":"Disease","text":["hypocellular marrow"],"offsets":[[1310,1329]],"normalized":[{"db_name":"MESH","db_id":"D001855"}]},{"id":"14197","type":"Chemical","text":["AZT"],"offsets":[[1347,1350]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"14198","type":"Disease","text":["myelodysplastic 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{"id":"14279","document_id":"8742498","passages":[{"id":"14280","type":"title","text":["Influence of diet free of NAD-precursors on acetaminophen hepatotoxicity in mice."],"offsets":[[0,81]]},{"id":"14281","type":"abstract","text":["Recently, we demonstrated the hepatoprotective effects of nicotinic acid amide, a selective inhibitor of poly(ADP-ribose) polymerase (PARP; EC 2.4.2.30) on mice suffering from acetaminophen (AAP)-hepatitis, suggesting that the AAP-induced liver injury involves a step which depends on adenoribosylation. The present study investigates the effects of a diet free of precursors of NAD, the substrate on which PARP acts, in female NMRI mice with AAP hepatitis and evaluates the influence of simultaneous ethanol consumption in these animals. Liver injuries were quantified as serum activities of glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT). While AAP caused a 117-fold elevation of serum transaminase activities in mice kept on a standard laboratory diet, which was significantly exacerbated by ethanol and inhibited by nicotinic acid amide (NAA), adverse effects were noted in animals fed a diet free of precursors of NAD. In these animals, only minor increases of serum transaminase activities were measured in the presence of AAP, and unlike the exacerbation caused by ethanol in mice on a standard diet, the liver damage was inhibited by 50% by ethanol. A further 64% reduction of hepatitis was observed, when NAA was given to ethanol\/AAP-mice. Our results provide evidence that the AAP-induced hepatitis and its exacerbation by ethanol can either be reduced by end-product inhibition of PARP by NAA or by dietary depletion of the enzyme's substrate NAD. We see the main application of NAA as for the combinational use in pharmaceutical preparations of acetaminophen in order to avoid hepatic damage in patients treated with this widely used analgesic."],"offsets":[[82,1775]]}],"entities":[{"id":"14282","type":"Chemical","text":["NAD"],"offsets":[[26,29]],"normalized":[{"db_name":"MESH","db_id":"D009243"}]},{"id":"14283","type":"Chemical","text":["acetaminophen"],"offsets":[[44,57]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"14284","type":"Disease","text":["hepatotoxicity"],"offsets":[[58,72]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"14285","type":"Chemical","text":["nicotinic acid 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{"id":"14466","document_id":"2435991","passages":[{"id":"14467","type":"title","text":["Antiarrhythmic plasma concentrations of cibenzoline on canine ventricular arrhythmias."],"offsets":[[0,86]]},{"id":"14468","type":"abstract","text":["Using two-stage coronary ligation-, digitalis-, and adrenaline-induced canine ventricular arrhythmias, antiarrhythmic effects of cibenzoline were examined and the minimum effective plasma concentration for each arrhythmia model was determined. Cibenzoline suppressed all the arrhythmias, and the minimum effective plasma concentrations for arrhythmias induced by 24-h coronary ligation, 48-h coronary ligation, digitalis, and adrenaline were 1.9 +\/- 0.9 (by 8 mg\/kg i.v.), 1.6 +\/- 0.5 (by 8 mg\/kg i.v.), 0.6 +\/- 0.2 (by 2 mg\/kg i.v.), and 3.5 +\/- 1.3 (by 5 mg\/kg i.v.) micrograms\/ml, respectively (mean +\/- SDM, n = 6-7). The concentration for adrenaline-induced arrhythmia was significantly higher than those for the other types of arrhythmias. This pharmacological profile is similar to those of mexiletine and tocainide, and all three drugs have central nervous system (CNS) stimulant action. Because cibenzoline had only weak hypotensive and sinus node depressive effects and was found to be orally active when given to coronary ligation arrhythmia dogs, its clinical usefulness is expected."],"offsets":[[87,1182]]}],"entities":[{"id":"14469","type":"Chemical","text":["cibenzoline"],"offsets":[[40,51]],"normalized":[{"db_name":"MESH","db_id":"C032151"}]},{"id":"14470","type":"Disease","text":["ventricular arrhythmias"],"offsets":[[62,85]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"14471","type":"Chemical","text":["digitalis"],"offsets":[[123,132]],"normalized":[{"db_name":"MESH","db_id":"D004071"}]},{"id":"14472","type":"Chemical","text":["adrenaline"],"offsets":[[139,149]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"14473","type":"Disease","text":["ventricular arrhythmias"],"offsets":[[165,188]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"14474","type":"Chemical","text":["cibenzoline"],"offsets":[[216,227]],"normalized":[{"db_name":"MESH","db_id":"C032151"}]},{"id":"14475","type":"Disease","text":["arrhythmia"],"offsets":[[298,308]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"14476","type":"Chemical","text":["Cibenzoline"],"offsets":[[331,342]],"normalized":[{"db_name":"MESH","db_id":"C032151"}]},{"id":"14477","type":"Disease","text":["arrhythmias"],"offsets":[[362,373]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"14478","type":"Disease","text":["arrhythmias"],"offsets":[[427,438]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"14479","type":"Chemical","text":["digitalis"],"offsets":[[498,507]],"normalized":[{"db_name":"MESH","db_id":"D004071"}]},{"id":"14480","type":"Chemical","text":["adrenaline"],"offsets":[[513,523]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"14481","type":"Chemical","text":["adrenaline"],"offsets":[[731,741]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"14482","type":"Disease","text":["arrhythmia"],"offsets":[[750,760]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"14483","type":"Disease","text":["arrhythmias"],"offsets":[[820,831]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"14484","type":"Chemical","text":["mexiletine"],"offsets":[[885,895]],"normalized":[{"db_name":"MESH","db_id":"D008801"}]},{"id":"14485","type":"Chemical","text":["tocainide"],"offsets":[[900,909]],"normalized":[{"db_name":"MESH","db_id":"D016677"}]},{"id":"14486","type":"Chemical","text":["cibenzoline"],"offsets":[[991,1002]],"normalized":[{"db_name":"MESH","db_id":"C032151"}]},{"id":"14487","type":"Disease","text":["hypotensive"],"offsets":[[1017,1028]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"14488","type":"Disease","text":["depressive"],"offsets":[[1044,1054]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"14489","type":"Disease","text":["arrhythmia"],"offsets":[[1129,1139]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]}],"events":[],"coreferences":[],"relations":[{"id":"14490","type":"CID","arg1_id":"14472","arg2_id":"14470","normalized":[]},{"id":"14491","type":"CID","arg1_id":"14472","arg2_id":"14473","normalized":[]},{"id":"14492","type":"CID","arg1_id":"14472","arg2_id":"14475","normalized":[]},{"id":"14493","type":"CID","arg1_id":"14472","arg2_id":"14477","normalized":[]},{"id":"14494","type":"CID","arg1_id":"14472","arg2_id":"14478","normalized":[]},{"id":"14495","type":"CID","arg1_id":"14472","arg2_id":"14482","normalized":[]},{"id":"14496","type":"CID","arg1_id":"14472","arg2_id":"14483","normalized":[]},{"id":"14497","type":"CID","arg1_id":"14472","arg2_id":"14489","normalized":[]},{"id":"14498","type":"CID","arg1_id":"14480","arg2_id":"14470","normalized":[]},{"id":"14499","type":"CID","arg1_id":"14480","arg2_id":"14473","normalized":[]},{"id":"14500","type":"CID","arg1_id":"14480","arg2_id":"14475","normalized":[]},{"id":"14501","type":"CID","arg1_id":"14480","arg2_id":"14477","normalized":[]},{"id":"14502","type":"CID","arg1_id":"14480","arg2_id":"14478","normalized":[]},{"id":"14503","type":"CID","arg1_id":"14480","arg2_id":"14482","normalized":[]},{"id":"14504","type":"CID","arg1_id":"14480","arg2_id":"14483","normalized":[]},{"id":"14505","type":"CID","arg1_id":"14480","arg2_id":"14489","normalized":[]},{"id":"14506","type":"CID","arg1_id":"14481","arg2_id":"14470","normalized":[]},{"id":"14507","type":"CID","arg1_id":"14481","arg2_id":"14473","normalized":[]},{"id":"14508","type":"CID","arg1_id":"14481","arg2_id":"14475","normalized":[]},{"id":"14509","type":"CID","arg1_id":"14481","arg2_id":"14477","normalized":[]},{"id":"14510","type":"CID","arg1_id":"14481","arg2_id":"14478","normalized":[]},{"id":"14511","type":"CID","arg1_id":"14481","arg2_id":"14482","normalized":[]},{"id":"14512","type":"CID","arg1_id":"14481","arg2_id":"14483","normalized":[]},{"id":"14513","type":"CID","arg1_id":"14481","arg2_id":"14489","normalized":[]},{"id":"14514","type":"CID","arg1_id":"14471","arg2_id":"14470","normalized":[]},{"id":"14515","type":"CID","arg1_id":"14471","arg2_id":"14473","normalized":[]},{"id":"14516","type":"CID","arg1_id":"14471","arg2_id":"14475","normalized":[]},{"id":"14517","type":"CID","arg1_id":"14471","arg2_id":"14477","normalized":[]},{"id":"14518","type":"CID","arg1_id":"14471","arg2_id":"14478","normalized":[]},{"id":"14519","type":"CID","arg1_id":"14471","arg2_id":"14482","normalized":[]},{"id":"14520","type":"CID","arg1_id":"14471","arg2_id":"14483","normalized":[]},{"id":"14521","type":"CID","arg1_id":"14471","arg2_id":"14489","normalized":[]},{"id":"14522","type":"CID","arg1_id":"14479","arg2_id":"14470","normalized":[]},{"id":"14523","type":"CID","arg1_id":"14479","arg2_id":"14473","normalized":[]},{"id":"14524","type":"CID","arg1_id":"14479","arg2_id":"14475","normalized":[]},{"id":"14525","type":"CID","arg1_id":"14479","arg2_id":"14477","normalized":[]},{"id":"14526","type":"CID","arg1_id":"14479","arg2_id":"14478","normalized":[]},{"id":"14527","type":"CID","arg1_id":"14479","arg2_id":"14482","normalized":[]},{"id":"14528","type":"CID","arg1_id":"14479","arg2_id":"14483","normalized":[]},{"id":"14529","type":"CID","arg1_id":"14479","arg2_id":"14489","normalized":[]}]}
{"id":"14530","document_id":"950631","passages":[{"id":"14531","type":"title","text":["Immunopathology of penicillamine-induced glomerular disease."],"offsets":[[0,60]]},{"id":"14532","type":"abstract","text":["Four patients with rheumatoid arthritis developed heavy proteinuria after five to 12 months of treatment with D-penicillamine. Light microscopy of renal biopsy samples showed minimal glomerular capillary wall thickening and mesangial matrix increase, or no departure from normal. Electron microscopy, however, revealed subepithelial electron-dense deposits, fusion of epithelial cell foot processes, and evidence of mesangial cell hyperactivity. Immunofluorescence microscopy demonstrated granular capillary wall deposits of IgG and C3. The findings were similar to those in early membranous glomerulonephritis, differences being observed however in the results of staining for the early-acting complement components C1q and C4. It is tentatively concluded that complement was activated by the classical pathway."],"offsets":[[61,873]]}],"entities":[{"id":"14533","type":"Chemical","text":["penicillamine"],"offsets":[[19,32]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"14534","type":"Disease","text":["glomerular disease"],"offsets":[[41,59]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"14535","type":"Disease","text":["rheumatoid arthritis"],"offsets":[[80,100]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"14536","type":"Disease","text":["proteinuria"],"offsets":[[117,128]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"14537","type":"Chemical","text":["D-penicillamine"],"offsets":[[171,186]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"14538","type":"Disease","text":["membranous glomerulonephritis"],"offsets":[[642,671]],"normalized":[{"db_name":"MESH","db_id":"D015433"}]}],"events":[],"coreferences":[],"relations":[{"id":"14539","type":"CID","arg1_id":"14533","arg2_id":"14534","normalized":[]},{"id":"14540","type":"CID","arg1_id":"14537","arg2_id":"14534","normalized":[]},{"id":"14541","type":"CID","arg1_id":"14533","arg2_id":"14536","normalized":[]},{"id":"14542","type":"CID","arg1_id":"14537","arg2_id":"14536","normalized":[]}]}
{"id":"14543","document_id":"663266","passages":[{"id":"14544","type":"title","text":["Ventricular fibrillation from diatrizoate with and without chelating agents."],"offsets":[[0,76]]},{"id":"14545","type":"abstract","text":["The toxicity of Renografin 76% was compared with that of Hypaque 76% by selective injection of each into the right coronary artery of dogs. Renografin contains the chelating agents sodium citrate and disodium edetate, while Hypaque contains calcium disodium edetate and no sodium citrate. Ventricular fibrillation occurred significantly more often with Renografin, suggesting that chelating agents contribute to toxicity in coronary angiography."],"offsets":[[77,522]]}],"entities":[{"id":"14546","type":"Disease","text":["Ventricular fibrillation"],"offsets":[[0,24]],"normalized":[{"db_name":"MESH","db_id":"D014693"}]},{"id":"14547","type":"Chemical","text":["diatrizoate"],"offsets":[[30,41]],"normalized":[{"db_name":"MESH","db_id":"D003973"}]},{"id":"14548","type":"Disease","text":["toxicity"],"offsets":[[81,89]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"14549","type":"Chemical","text":["Renografin 76%"],"offsets":[[93,107]],"normalized":[{"db_name":"MESH","db_id":"C027278"}]},{"id":"14550","type":"Chemical","text":["Hypaque 76%"],"offsets":[[134,145]],"normalized":[{"db_name":"MESH","db_id":"C027278"}]},{"id":"14551","type":"Chemical","text":["Renografin"],"offsets":[[217,227]],"normalized":[{"db_name":"MESH","db_id":"D003974"}]},{"id":"14552","type":"Chemical","text":["sodium citrate"],"offsets":[[258,272]],"normalized":[{"db_name":"MESH","db_id":"C102006"}]},{"id":"14553","type":"Chemical","text":["disodium edetate"],"offsets":[[277,293]],"normalized":[{"db_name":"MESH","db_id":"D004492"}]},{"id":"14554","type":"Chemical","text":["Hypaque"],"offsets":[[301,308]],"normalized":[{"db_name":"MESH","db_id":"D003973"}]},{"id":"14555","type":"Chemical","text":["calcium disodium edetate"],"offsets":[[318,342]],"normalized":[{"db_name":"MESH","db_id":"D004492"}]},{"id":"14556","type":"Chemical","text":["sodium citrate"],"offsets":[[350,364]],"normalized":[{"db_name":"MESH","db_id":"C102006"}]},{"id":"14557","type":"Disease","text":["Ventricular fibrillation"],"offsets":[[366,390]],"normalized":[{"db_name":"MESH","db_id":"D014693"}]},{"id":"14558","type":"Chemical","text":["Renografin"],"offsets":[[430,440]],"normalized":[{"db_name":"MESH","db_id":"D003974"}]},{"id":"14559","type":"Disease","text":["toxicity"],"offsets":[[489,497]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]}],"events":[],"coreferences":[],"relations":[{"id":"14560","type":"CID","arg1_id":"14549","arg2_id":"14546","normalized":[]},{"id":"14561","type":"CID","arg1_id":"14549","arg2_id":"14557","normalized":[]},{"id":"14562","type":"CID","arg1_id":"14550","arg2_id":"14546","normalized":[]},{"id":"14563","type":"CID","arg1_id":"14550","arg2_id":"14557","normalized":[]},{"id":"14564","type":"CID","arg1_id":"14552","arg2_id":"14546","normalized":[]},{"id":"14565","type":"CID","arg1_id":"14552","arg2_id":"14557","normalized":[]},{"id":"14566","type":"CID","arg1_id":"14556","arg2_id":"14546","normalized":[]},{"id":"14567","type":"CID","arg1_id":"14556","arg2_id":"14557","normalized":[]},{"id":"14568","type":"CID","arg1_id":"14553","arg2_id":"14546","normalized":[]},{"id":"14569","type":"CID","arg1_id":"14553","arg2_id":"14557","normalized":[]},{"id":"14570","type":"CID","arg1_id":"14555","arg2_id":"14546","normalized":[]},{"id":"14571","type":"CID","arg1_id":"14555","arg2_id":"14557","normalized":[]}]}
{"id":"14572","document_id":"19319147","passages":[{"id":"14573","type":"title","text":["Rapid reversal of anticoagulation reduces hemorrhage volume in a mouse model of warfarin-associated intracerebral hemorrhage."],"offsets":[[0,125]]},{"id":"14574","type":"abstract","text":["Warfarin-associated intracerebral hemorrhage (W-ICH) is a severe type of stroke. There is no consensus on the optimal treatment for W-ICH. Using a mouse model, we tested whether the rapid reversal of anticoagulation using human prothrombin complex concentrate (PCC) can reduce hemorrhagic blood volume. Male CD-1 mice were treated with warfarin (2 mg\/kg over 24 h), resulting in a mean (+\/-s.d.) International Normalized Ratio of 3.5+\/-0.9. First, we showed that an intravenous administration of human PCC rapidly reversed anticoagulation in mice. Second, a stereotactic injection of collagenase was administered to induce hemorrhage in the right striatum. Forty-five minutes later, the animals were randomly treated with PCC (100 U\/kg) or saline i.v. (n=12 per group). Twenty-four hours after hemorrhage induction, hemorrhagic blood volume was quantified using a photometric hemoglobin assay. The mean hemorrhagic blood volume was reduced in PCC-treated animals (6.5+\/-3.1 microL) compared with saline controls (15.3+\/-11.2 microL, P=0.015). In the saline group, 45% of the mice developed large hematomas (i.e., >15 microL). In contrast, such extensive lesions were never found in the PCC group. We provide experimental data suggesting PCC to be an effective acute treatment for W-ICH in terms of reducing hemorrhagic blood volume. Future studies are needed to assess the therapeutic potential emerging from our finding for human W-ICH."],"offsets":[[126,1563]]}],"entities":[{"id":"14575","type":"Disease","text":["hemorrhage"],"offsets":[[42,52]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"14576","type":"Chemical","text":["warfarin"],"offsets":[[80,88]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"14577","type":"Disease","text":["intracerebral hemorrhage"],"offsets":[[100,124]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"14578","type":"Chemical","text":["Warfarin"],"offsets":[[126,134]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"14579","type":"Disease","text":["intracerebral hemorrhage"],"offsets":[[146,170]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"14580","type":"Disease","text":["ICH"],"offsets":[[174,177]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"14581","type":"Disease","text":["stroke"],"offsets":[[199,205]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"14582","type":"Disease","text":["ICH"],"offsets":[[260,263]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"14583","type":"Chemical","text":["prothrombin complex concentrate"],"offsets":[[354,385]],"normalized":[{"db_name":"MESH","db_id":"C025667"}]},{"id":"14584","type":"Chemical","text":["PCC"],"offsets":[[387,390]],"normalized":[{"db_name":"MESH","db_id":"C025667"}]},{"id":"14585","type":"Chemical","text":["warfarin"],"offsets":[[462,470]],"normalized":[{"db_name":"MESH","db_id":"D014859"}]},{"id":"14586","type":"Chemical","text":["PCC"],"offsets":[[628,631]],"normalized":[{"db_name":"MESH","db_id":"C025667"}]},{"id":"14587","type":"Disease","text":["hemorrhage"],"offsets":[[749,759]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"14588","type":"Chemical","text":["PCC"],"offsets":[[848,851]],"normalized":[{"db_name":"MESH","db_id":"C025667"}]},{"id":"14589","type":"Disease","text":["hemorrhage"],"offsets":[[920,930]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"14590","type":"Chemical","text":["PCC"],"offsets":[[1069,1072]],"normalized":[{"db_name":"MESH","db_id":"C025667"}]},{"id":"14591","type":"Disease","text":["hematomas"],"offsets":[[1222,1231]],"normalized":[{"db_name":"MESH","db_id":"D006406"}]},{"id":"14592","type":"Chemical","text":["PCC"],"offsets":[[1312,1315]],"normalized":[{"db_name":"MESH","db_id":"C025667"}]},{"id":"14593","type":"Chemical","text":["PCC"],"offsets":[[1363,1366]],"normalized":[{"db_name":"MESH","db_id":"C025667"}]},{"id":"14594","type":"Disease","text":["ICH"],"offsets":[[1408,1411]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]},{"id":"14595","type":"Disease","text":["ICH"],"offsets":[[1559,1562]],"normalized":[{"db_name":"MESH","db_id":"D002543"}]}],"events":[],"coreferences":[],"relations":[{"id":"14596","type":"CID","arg1_id":"14576","arg2_id":"14577","normalized":[]},{"id":"14597","type":"CID","arg1_id":"14576","arg2_id":"14579","normalized":[]},{"id":"14598","type":"CID","arg1_id":"14576","arg2_id":"14580","normalized":[]},{"id":"14599","type":"CID","arg1_id":"14576","arg2_id":"14582","normalized":[]},{"id":"14600","type":"CID","arg1_id":"14576","arg2_id":"14594","normalized":[]},{"id":"14601","type":"CID","arg1_id":"14576","arg2_id":"14595","normalized":[]},{"id":"14602","type":"CID","arg1_id":"14578","arg2_id":"14577","normalized":[]},{"id":"14603","type":"CID","arg1_id":"14578","arg2_id":"14579","normalized":[]},{"id":"14604","type":"CID","arg1_id":"14578","arg2_id":"14580","normalized":[]},{"id":"14605","type":"CID","arg1_id":"14578","arg2_id":"14582","normalized":[]},{"id":"14606","type":"CID","arg1_id":"14578","arg2_id":"14594","normalized":[]},{"id":"14607","type":"CID","arg1_id":"14578","arg2_id":"14595","normalized":[]},{"id":"14608","type":"CID","arg1_id":"14585","arg2_id":"14577","normalized":[]},{"id":"14609","type":"CID","arg1_id":"14585","arg2_id":"14579","normalized":[]},{"id":"14610","type":"CID","arg1_id":"14585","arg2_id":"14580","normalized":[]},{"id":"14611","type":"CID","arg1_id":"14585","arg2_id":"14582","normalized":[]},{"id":"14612","type":"CID","arg1_id":"14585","arg2_id":"14594","normalized":[]},{"id":"14613","type":"CID","arg1_id":"14585","arg2_id":"14595","normalized":[]}]}
{"id":"14614","document_id":"16634859","passages":[{"id":"14615","type":"title","text":["Impact of alcohol exposure after pregnancy recognition on ultrasonographic fetal growth measures."],"offsets":[[0,97]]},{"id":"14616","type":"abstract","text":["BACKGROUND: More than 3 decades after Jones and Smith (1973) reported on the devastation caused by alcohol exposure on fetal development, the rates of heavy drinking during pregnancy remain relatively unchanged. Early identification of fetal alcohol exposure and maternal abstinence led to better infant outcomes. This study examined the utility of biometry for detecting alcohol-related fetal growth impairment. METHODS: We obtained fetal ultrasound measures from routine ultrasound examinations for 167 pregnant hazardous drinkers who were enrolled in a brief alcohol intervention study. The fetal measures for women who quit after learning of their pregnancies were compared with measures for women who continued some drinking throughout the course of their pregnancies. Because intensity of alcohol consumption is associated with poorer fetal outcomes, separate analyses were conducted for the heavy (average of >or=5 drinks per drinking day) alcohol consumers. Fetal measures from the heavy-exposed fetuses were also compared with measures from a nondrinking group that was representative of normal, uncomplicated pregnancies from our clinics. Analyses of covariance were used to determine whether there were differences between groups after controlling for influences of gestational age and drug abuse. RESULTS: Nearly half of the pregnant drinkers abstained after learning of their pregnancies. When women reportedly quit drinking early in their pregnancies, fetal growth measures were not significantly different from a non-alcohol-exposed group, regardless of prior drinking patterns. Any alcohol consumption postpregnancy recognition among the heavy drinkers resulted in reduced cerebellar growth as well as decreased cranial to body growth in comparison with women who either quit drinking or who were nondrinkers. Amphetamine abuse was predictive of larger cranial to body growth ratios. CONCLUSIONS: Alterations in fetal biometric measurements were observed among the heavy drinkers only when they continued drinking after becoming aware of their pregnancies. Although the reliance on self-reported drinking is a limitation in this study, these findings support the benefits of early abstinence and the potential for ultrasound examinations in the detection of fetal alcohol effects."],"offsets":[[98,2394]]}],"entities":[{"id":"14617","type":"Chemical","text":["alcohol"],"offsets":[[10,17]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"14618","type":"Chemical","text":["alcohol"],"offsets":[[197,204]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"14619","type":"Chemical","text":["alcohol"],"offsets":[[340,347]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"14620","type":"Chemical","text":["alcohol"],"offsets":[[470,477]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"14621","type":"Disease","text":["growth impairment"],"offsets":[[492,509]],"normalized":[{"db_name":"MESH","db_id":"D006130"}]},{"id":"14622","type":"Chemical","text":["alcohol"],"offsets":[[660,667]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"14623","type":"Chemical","text":["alcohol"],"offsets":[[893,900]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"14624","type":"Chemical","text":["alcohol"],"offsets":[[1045,1052]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"14625","type":"Disease","text":["drug abuse"],"offsets":[[1395,1405]],"normalized":[{"db_name":"MESH","db_id":"D019966"}]},{"id":"14626","type":"Chemical","text":["alcohol"],"offsets":[[1630,1637]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"14627","type":"Chemical","text":["alcohol"],"offsets":[[1696,1703]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"14628","type":"Disease","text":["reduced cerebellar growth"],"offsets":[[1779,1804]],"normalized":[{"db_name":"MESH","db_id":"D006130"}]},{"id":"14629","type":"Disease","text":["decreased cranial to body growth"],"offsets":[[1816,1848]],"normalized":[{"db_name":"MESH","db_id":"D006130"}]},{"id":"14630","type":"Chemical","text":["Amphetamine"],"offsets":[[1924,1935]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"14631","type":"Chemical","text":["alcohol"],"offsets":[[2378,2385]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]}],"events":[],"coreferences":[],"relations":[{"id":"14632","type":"CID","arg1_id":"14617","arg2_id":"14621","normalized":[]},{"id":"14633","type":"CID","arg1_id":"14617","arg2_id":"14628","normalized":[]},{"id":"14634","type":"CID","arg1_id":"14617","arg2_id":"14629","normalized":[]},{"id":"14635","type":"CID","arg1_id":"14618","arg2_id":"14621","normalized":[]},{"id":"14636","type":"CID","arg1_id":"14618","arg2_id":"14628","normalized":[]},{"id":"14637","type":"CID","arg1_id":"14618","arg2_id":"14629","normalized":[]},{"id":"14638","type":"CID","arg1_id":"14619","arg2_id":"14621","normalized":[]},{"id":"14639","type":"CID","arg1_id":"14619","arg2_id":"14628","normalized":[]},{"id":"14640","type":"CID","arg1_id":"14619","arg2_id":"14629","normalized":[]},{"id":"14641","type":"CID","arg1_id":"14620","arg2_id":"14621","normalized":[]},{"id":"14642","type":"CID","arg1_id":"14620","arg2_id":"14628","normalized":[]},{"id":"14643","type":"CID","arg1_id":"14620","arg2_id":"14629","normalized":[]},{"id":"14644","type":"CID","arg1_id":"14622","arg2_id":"14621","normalized":[]},{"id":"14645","type":"CID","arg1_id":"14622","arg2_id":"14628","normalized":[]},{"id":"14646","type":"CID","arg1_id":"14622","arg2_id":"14629","normalized":[]},{"id":"14647","type":"CID","arg1_id":"14623","arg2_id":"14621","normalized":[]},{"id":"14648","type":"CID","arg1_id":"14623","arg2_id":"14628","normalized":[]},{"id":"14649","type":"CID","arg1_id":"14623","arg2_id":"14629","normalized":[]},{"id":"14650","type":"CID","arg1_id":"14624","arg2_id":"14621","normalized":[]},{"id":"14651","type":"CID","arg1_id":"14624","arg2_id":"14628","normalized":[]},{"id":"14652","type":"CID","arg1_id":"14624","arg2_id":"14629","normalized":[]},{"id":"14653","type":"CID","arg1_id":"14626","arg2_id":"14621","normalized":[]},{"id":"14654","type":"CID","arg1_id":"14626","arg2_id":"14628","normalized":[]},{"id":"14655","type":"CID","arg1_id":"14626","arg2_id":"14629","normalized":[]},{"id":"14656","type":"CID","arg1_id":"14627","arg2_id":"14621","normalized":[]},{"id":"14657","type":"CID","arg1_id":"14627","arg2_id":"14628","normalized":[]},{"id":"14658","type":"CID","arg1_id":"14627","arg2_id":"14629","normalized":[]},{"id":"14659","type":"CID","arg1_id":"14631","arg2_id":"14621","normalized":[]},{"id":"14660","type":"CID","arg1_id":"14631","arg2_id":"14628","normalized":[]},{"id":"14661","type":"CID","arg1_id":"14631","arg2_id":"14629","normalized":[]},{"id":"14662","type":"CID","arg1_id":"14630","arg2_id":"14621","normalized":[]},{"id":"14663","type":"CID","arg1_id":"14630","arg2_id":"14628","normalized":[]},{"id":"14664","type":"CID","arg1_id":"14630","arg2_id":"14629","normalized":[]}]}
{"id":"14665","document_id":"16471092","passages":[{"id":"14666","type":"title","text":["Urinary symptoms and quality of life changes in Thai women with overactive bladder after tolterodine treatment."],"offsets":[[0,111]]},{"id":"14667","type":"abstract","text":["OBJECTIVES: To study the urinary symptoms and quality of life changes in Thai women with overactive bladder (OAB) after tolterodine treatment. MATERIAL AND METHOD: Thirty women (aged 30-77 years) diagnosed as having OAB at the Gynecology Clinic, King Chulalongkorn Memorial Hospital from January to April 2004 were included in the present study. Tolterodine 2 mg, twice daily was given. After 8 weeks treatment, changes in micturition diary variables and tolerability were determined. Short form 36 (SF36) questionaires (Thai version) were given before and after 8 weeks of treatment. RESULTS: At 8 weeks, all micturition per day decreased from 16. 7 +\/- 5. 3 to 6. 7 +\/- 2.4 times per day. The number of nocturia episodes decreased from 5.4 +\/- 4.2 to 1.1 +\/- 1.0 times per night. The most common side effect was dry month in 5 cases (16.7%) with 2 cases reporting a moderate degree and 1 case with severe degree. Only one case (3.3%) withdrew from the present study due to a severe dry mouth. The SF-36 scores changed significantly in the domains of physical functioning, role function emotional, social function and mental heath. CONCLUSION: Tolterodine was well tolerated and its effects improved the quality of life in Thai women with OAB."],"offsets":[[112,1356]]}],"entities":[{"id":"14668","type":"Disease","text":["overactive bladder"],"offsets":[[64,82]],"normalized":[{"db_name":"MESH","db_id":"D053201"}]},{"id":"14669","type":"Chemical","text":["tolterodine"],"offsets":[[89,100]],"normalized":[{"db_name":"MESH","db_id":"C099041"}]},{"id":"14670","type":"Disease","text":["overactive bladder"],"offsets":[[201,219]],"normalized":[{"db_name":"MESH","db_id":"D053201"}]},{"id":"14671","type":"Disease","text":["OAB"],"offsets":[[221,224]],"normalized":[{"db_name":"MESH","db_id":"D053201"}]},{"id":"14672","type":"Chemical","text":["tolterodine"],"offsets":[[232,243]],"normalized":[{"db_name":"MESH","db_id":"C099041"}]},{"id":"14673","type":"Disease","text":["OAB"],"offsets":[[328,331]],"normalized":[{"db_name":"MESH","db_id":"D053201"}]},{"id":"14674","type":"Chemical","text":["Tolterodine"],"offsets":[[458,469]],"normalized":[{"db_name":"MESH","db_id":"C099041"}]},{"id":"14675","type":"Disease","text":["nocturia"],"offsets":[[817,825]],"normalized":[{"db_name":"MESH","db_id":"D053158"}]},{"id":"14676","type":"Disease","text":["dry month"],"offsets":[[926,935]],"normalized":[{"db_name":"MESH","db_id":"D014987"}]},{"id":"14677","type":"Disease","text":["dry mouth"],"offsets":[[1096,1105]],"normalized":[{"db_name":"MESH","db_id":"D014987"}]},{"id":"14678","type":"Chemical","text":["Tolterodine"],"offsets":[[1257,1268]],"normalized":[{"db_name":"MESH","db_id":"C099041"}]},{"id":"14679","type":"Disease","text":["OAB"],"offsets":[[1352,1355]],"normalized":[{"db_name":"MESH","db_id":"D053201"}]}],"events":[],"coreferences":[],"relations":[{"id":"14680","type":"CID","arg1_id":"14669","arg2_id":"14676","normalized":[]},{"id":"14681","type":"CID","arg1_id":"14669","arg2_id":"14677","normalized":[]},{"id":"14682","type":"CID","arg1_id":"14672","arg2_id":"14676","normalized":[]},{"id":"14683","type":"CID","arg1_id":"14672","arg2_id":"14677","normalized":[]},{"id":"14684","type":"CID","arg1_id":"14674","arg2_id":"14676","normalized":[]},{"id":"14685","type":"CID","arg1_id":"14674","arg2_id":"14677","normalized":[]},{"id":"14686","type":"CID","arg1_id":"14678","arg2_id":"14676","normalized":[]},{"id":"14687","type":"CID","arg1_id":"14678","arg2_id":"14677","normalized":[]}]}
{"id":"14688","document_id":"16174948","passages":[{"id":"14689","type":"title","text":["Absence of acute cerebral vasoconstriction after cocaine-associated subarachnoid hemorrhage."],"offsets":[[0,92]]},{"id":"14690","type":"abstract","text":["INTRODUCTION: Cocaine use has been associated with neurovascular complications, including arterial vasoconstriction and vasculitis. However, there are few studies of angiographic effects of cocaine on human cerebral arteries. Information on these effects could be obtained from angiograms of patients with cocaine-associated subarachnoid hemorrhage (SAH) who underwent angiography shortly after cocaine use. METHODS: We screened patients with SAH retrospectively and identified those with positive urine toxicology for cocaine or its metabolites. Quantitative arterial diameter measurements from angiograms of these patients were compared to measurements from control patients with SAH who were matched for factors known to influence arterial diameter. Qualitative comparisons of small artery changes also were made. RESULTS: Thirteen patients with positive cocaine toxicology were compared to 26 controls. There were no significant differences between groups in the mean diameters of the intradural internal carotid, sphenoidal segment of the middle cerebral, precommunicating segment of the anterior cerebral, or basilar arteries (p greater than 0.05 for all comparisons, unpaired t-tests). There also were no significant differences between groups when expressing diameters as the sum of the precommunicating segment of the anterior cerebral + sphenoidal segment of the middle cerebral + supraclinoid internal carotid artery + basilar artery divided by the diameter of the petrous internal carotid artery (p greater than 0.05, unpaired t-tests). Qualitative assessments showed two arterial irregularities in the distal vasculature in each group. CONCLUSION: No quantitative evidence for narrowing of large cerebral arteries or qualitative angiographic evidence for distal narrowing or vasculitis could be found in patients who underwent angiography after aneurysmal SAH associated with cocaine use."],"offsets":[[93,1994]]}],"entities":[{"id":"14691","type":"Chemical","text":["cocaine"],"offsets":[[49,56]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"14692","type":"Disease","text":["subarachnoid hemorrhage"],"offsets":[[68,91]],"normalized":[{"db_name":"MESH","db_id":"D013345"}]},{"id":"14693","type":"Chemical","text":["Cocaine"],"offsets":[[107,114]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"14694","type":"Disease","text":["neurovascular complications"],"offsets":[[144,171]],"normalized":[{"db_name":"MESH","db_id":"D013901"}]},{"id":"14695","type":"Disease","text":["vasculitis"],"offsets":[[213,223]],"normalized":[{"db_name":"MESH","db_id":"D014657"}]},{"id":"14696","type":"Chemical","text":["cocaine"],"offsets":[[283,290]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"14697","type":"Chemical","text":["cocaine"],"offsets":[[399,406]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"14698","type":"Disease","text":["subarachnoid hemorrhage"],"offsets":[[418,441]],"normalized":[{"db_name":"MESH","db_id":"D013345"}]},{"id":"14699","type":"Disease","text":["SAH"],"offsets":[[443,446]],"normalized":[{"db_name":"MESH","db_id":"D013345"}]},{"id":"14700","type":"Chemical","text":["cocaine"],"offsets":[[488,495]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"14701","type":"Disease","text":["SAH"],"offsets":[[536,539]],"normalized":[{"db_name":"MESH","db_id":"D013345"}]},{"id":"14702","type":"Chemical","text":["cocaine"],"offsets":[[612,619]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"14703","type":"Disease","text":["SAH"],"offsets":[[775,778]],"normalized":[{"db_name":"MESH","db_id":"D013345"}]},{"id":"14704","type":"Chemical","text":["cocaine"],"offsets":[[951,958]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"14705","type":"Disease","text":["vasculitis"],"offsets":[[1881,1891]],"normalized":[{"db_name":"MESH","db_id":"D014657"}]},{"id":"14706","type":"Disease","text":["aneurysmal"],"offsets":[[1951,1961]],"normalized":[{"db_name":"MESH","db_id":"D017542"}]},{"id":"14707","type":"Disease","text":["SAH"],"offsets":[[1962,1965]],"normalized":[{"db_name":"MESH","db_id":"D013345"}]},{"id":"14708","type":"Chemical","text":["cocaine"],"offsets":[[1982,1989]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]}],"events":[],"coreferences":[],"relations":[{"id":"14709","type":"CID","arg1_id":"14691","arg2_id":"14706","normalized":[]},{"id":"14710","type":"CID","arg1_id":"14693","arg2_id":"14706","normalized":[]},{"id":"14711","type":"CID","arg1_id":"14696","arg2_id":"14706","normalized":[]},{"id":"14712","type":"CID","arg1_id":"14697","arg2_id":"14706","normalized":[]},{"id":"14713","type":"CID","arg1_id":"14700","arg2_id":"14706","normalized":[]},{"id":"14714","type":"CID","arg1_id":"14702","arg2_id":"14706","normalized":[]},{"id":"14715","type":"CID","arg1_id":"14704","arg2_id":"14706","normalized":[]},{"id":"14716","type":"CID","arg1_id":"14708","arg2_id":"14706","normalized":[]},{"id":"14717","type":"CID","arg1_id":"14691","arg2_id":"14692","normalized":[]},{"id":"14718","type":"CID","arg1_id":"14691","arg2_id":"14698","normalized":[]},{"id":"14719","type":"CID","arg1_id":"14691","arg2_id":"14699","normalized":[]},{"id":"14720","type":"CID","arg1_id":"14691","arg2_id":"14701","normalized":[]},{"id":"14721","type":"CID","arg1_id":"14691","arg2_id":"14703","normalized":[]},{"id":"14722","type":"CID","arg1_id":"14691","arg2_id":"14707","normalized":[]},{"id":"14723","type":"CID","arg1_id":"14693","arg2_id":"14692","normalized":[]},{"id":"14724","type":"CID","arg1_id":"14693","arg2_id":"14698","normalized":[]},{"id":"14725","type":"CID","arg1_id":"14693","arg2_id":"14699","normalized":[]},{"id":"14726","type":"CID","arg1_id":"14693","arg2_id":"14701","normalized":[]},{"id":"14727","type":"CID","arg1_id":"14693","arg2_id":"14703","normalized":[]},{"id":"14728","type":"CID","arg1_id":"14693","arg2_id":"14707","normalized":[]},{"id":"14729","type":"CID","arg1_id":"14696","arg2_id":"14692","normalized":[]},{"id":"14730","type":"CID","arg1_id":"14696","arg2_id":"14698","normalized":[]},{"id":"14731","type":"CID","arg1_id":"14696","arg2_id":"14699","normalized":[]},{"id":"14732","type":"CID","arg1_id":"14696","arg2_id":"14701","normalized":[]},{"id":"14733","type":"CID","arg1_id":"14696","arg2_id":"14703","normalized":[]},{"id":"14734","type":"CID","arg1_id":"14696","arg2_id":"14707","normalized":[]},{"id":"14735","type":"CID","arg1_id":"14697","arg2_id":"14692","normalized":[]},{"id":"14736","type":"CID","arg1_id":"14697","arg2_id":"14698","normalized":[]},{"id":"14737","type":"CID","arg1_id":"14697","arg2_id":"14699","normalized":[]},{"id":"14738","type":"CID","arg1_id":"14697","arg2_id":"14701","normalized":[]},{"id":"14739","type":"CID","arg1_id":"14697","arg2_id":"14703","normalized":[]},{"id":"14740","type":"CID","arg1_id":"14697","arg2_id":"14707","normalized":[]},{"id":"14741","type":"CID","arg1_id":"14700","arg2_id":"14692","normalized":[]},{"id":"14742","type":"CID","arg1_id":"14700","arg2_id":"14698","normalized":[]},{"id":"14743","type":"CID","arg1_id":"14700","arg2_id":"14699","normalized":[]},{"id":"14744","type":"CID","arg1_id":"14700","arg2_id":"14701","normalized":[]},{"id":"14745","type":"CID","arg1_id":"14700","arg2_id":"14703","normalized":[]},{"id":"14746","type":"CID","arg1_id":"14700","arg2_id":"14707","normalized":[]},{"id":"14747","type":"CID","arg1_id":"14702","arg2_id":"14692","normalized":[]},{"id":"14748","type":"CID","arg1_id":"14702","arg2_id":"14698","normalized":[]},{"id":"14749","type":"CID","arg1_id":"14702","arg2_id":"14699","normalized":[]},{"id":"14750","type":"CID","arg1_id":"14702","arg2_id":"14701","normalized":[]},{"id":"14751","type":"CID","arg1_id":"14702","arg2_id":"14703","normalized":[]},{"id":"14752","type":"CID","arg1_id":"14702","arg2_id":"14707","normalized":[]},{"id":"14753","type":"CID","arg1_id":"14704","arg2_id":"14692","normalized":[]},{"id":"14754","type":"CID","arg1_id":"14704","arg2_id":"14698","normalized":[]},{"id":"14755","type":"CID","arg1_id":"14704","arg2_id":"14699","normalized":[]},{"id":"14756","type":"CID","arg1_id":"14704","arg2_id":"14701","normalized":[]},{"id":"14757","type":"CID","arg1_id":"14704","arg2_id":"14703","normalized":[]},{"id":"14758","type":"CID","arg1_id":"14704","arg2_id":"14707","normalized":[]},{"id":"14759","type":"CID","arg1_id":"14708","arg2_id":"14692","normalized":[]},{"id":"14760","type":"CID","arg1_id":"14708","arg2_id":"14698","normalized":[]},{"id":"14761","type":"CID","arg1_id":"14708","arg2_id":"14699","normalized":[]},{"id":"14762","type":"CID","arg1_id":"14708","arg2_id":"14701","normalized":[]},{"id":"14763","type":"CID","arg1_id":"14708","arg2_id":"14703","normalized":[]},{"id":"14764","type":"CID","arg1_id":"14708","arg2_id":"14707","normalized":[]}]}
{"id":"14765","document_id":"15042318","passages":[{"id":"14766","type":"title","text":["Atrial fibrillation following chemotherapy for stage IIIE diffuse large B-cell gastric lymphoma in a patient with myotonic dystrophy (Steinert's disease)."],"offsets":[[0,154]]},{"id":"14767","type":"abstract","text":["The authors describe the unusual association between diffuse B-cell gastric lymphoma and myotonic dystrophy, the most common form of adult muscular dystrophy, and sudden atrial fibrillation following one cycle of doxorubicin-based chemotherapy in the same patient. Atrial fibrillation or other cardiac arrhythmias are unusual complications in patients treated with chemotherapy. The cardiac toxicity intrinsically associated with the aggressive chemotherapy employed could function as a triggering factor for the arrhythmia in the predisposed myocardium of this patient."],"offsets":[[155,725]]}],"entities":[{"id":"14768","type":"Disease","text":["Atrial fibrillation"],"offsets":[[0,19]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"14769","type":"Disease","text":["gastric lymphoma"],"offsets":[[79,95]],"normalized":[{"db_name":"MESH","db_id":"C535648"}]},{"id":"14770","type":"Disease","text":["myotonic dystrophy"],"offsets":[[114,132]],"normalized":[{"db_name":"MESH","db_id":"D009223"}]},{"id":"14771","type":"Disease","text":["Steinert's disease"],"offsets":[[134,152]],"normalized":[{"db_name":"MESH","db_id":"D009223"}]},{"id":"14772","type":"Disease","text":["gastric lymphoma"],"offsets":[[223,239]],"normalized":[{"db_name":"MESH","db_id":"C535648"}]},{"id":"14773","type":"Disease","text":["myotonic dystrophy"],"offsets":[[244,262]],"normalized":[{"db_name":"MESH","db_id":"D009223"}]},{"id":"14774","type":"Disease","text":["muscular dystrophy"],"offsets":[[294,312]],"normalized":[{"db_name":"MESH","db_id":"D009136"}]},{"id":"14775","type":"Disease","text":["atrial fibrillation"],"offsets":[[325,344]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"14776","type":"Chemical","text":["doxorubicin"],"offsets":[[368,379]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"14777","type":"Disease","text":["Atrial fibrillation"],"offsets":[[420,439]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"14778","type":"Disease","text":["cardiac arrhythmias"],"offsets":[[449,468]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"14779","type":"Disease","text":["cardiac toxicity"],"offsets":[[538,554]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"14780","type":"Disease","text":["arrhythmia"],"offsets":[[668,678]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]}],"events":[],"coreferences":[],"relations":[{"id":"14781","type":"CID","arg1_id":"14776","arg2_id":"14768","normalized":[]},{"id":"14782","type":"CID","arg1_id":"14776","arg2_id":"14775","normalized":[]},{"id":"14783","type":"CID","arg1_id":"14776","arg2_id":"14777","normalized":[]}]}
{"id":"14784","document_id":"12448656","passages":[{"id":"14785","type":"title","text":["A phase II study of thalidomide in advanced metastatic renal cell carcinoma."],"offsets":[[0,76]]},{"id":"14786","type":"abstract","text":["OBJECTIVES: To evaluate the toxicity and activity of thalidomide in patients with advanced metastatic renal cell cancer and to measure changes of one angiogenic factor, vascular endothelial growth factor (VEGF)165, with therapy. PATIENTS AND METHODS: 29 patients were enrolled on a study of thalidomide using an intra-patient dose escalation schedule. Patients began thalidomide at 400 mg\/d and escalated as tolerated to 1200 mg\/d by day 54. Fifty-nine per cent of patients had had previous therapy with IL-2 and 52% were performance status 2 or 3. Systemic plasma VEGF165 levels were measured by dual monoclonal ELISA in 8 patients. RESULTS: 24 patients were evaluable for response with one partial response of 11 months duration of a patient with hepatic and pulmonary metastases (4%), one minor response, and 2 patients stable for over 6 months. Somnolence and constipation were prominent toxicities and most patients could not tolerate the 1200 mg\/day dose level. Systemic plasma VEGF165 levels did not change with therapy. CONCLUSION: These results are consistent with a low level of activity of thalidomide in renal cell carcinoma. Administration of doses over 800 mg\/day was difficult to achieve in this patient population, however lower doses were practical. The dose-response relationship, if any, of thalidomide for renal cell carcinoma is unclear."],"offsets":[[77,1435]]}],"entities":[{"id":"14787","type":"Chemical","text":["thalidomide"],"offsets":[[20,31]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"14788","type":"Disease","text":["renal cell carcinoma"],"offsets":[[55,75]],"normalized":[{"db_name":"MESH","db_id":"D002292"}]},{"id":"14789","type":"Disease","text":["toxicity"],"offsets":[[105,113]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"14790","type":"Chemical","text":["thalidomide"],"offsets":[[130,141]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"14791","type":"Disease","text":["renal cell cancer"],"offsets":[[179,196]],"normalized":[{"db_name":"MESH","db_id":"D002292"}]},{"id":"14792","type":"Chemical","text":["thalidomide"],"offsets":[[368,379]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"14793","type":"Chemical","text":["thalidomide"],"offsets":[[444,455]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"14794","type":"Disease","text":["metastases"],"offsets":[[848,858]],"normalized":[{"db_name":"MESH","db_id":"D009362"}]},{"id":"14795","type":"Disease","text":["Somnolence"],"offsets":[[926,936]],"normalized":[{"db_name":"MESH","db_id":"D006970"}]},{"id":"14796","type":"Disease","text":["constipation"],"offsets":[[941,953]],"normalized":[{"db_name":"MESH","db_id":"D003248"}]},{"id":"14797","type":"Disease","text":["toxicities"],"offsets":[[969,979]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"14798","type":"Chemical","text":["thalidomide"],"offsets":[[1178,1189]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"14799","type":"Disease","text":["renal cell carcinoma"],"offsets":[[1193,1213]],"normalized":[{"db_name":"MESH","db_id":"D002292"}]},{"id":"14800","type":"Chemical","text":["thalidomide"],"offsets":[[1387,1398]],"normalized":[{"db_name":"MESH","db_id":"D013792"}]},{"id":"14801","type":"Disease","text":["renal cell carcinoma"],"offsets":[[1403,1423]],"normalized":[{"db_name":"MESH","db_id":"D002292"}]}],"events":[],"coreferences":[],"relations":[{"id":"14802","type":"CID","arg1_id":"14787","arg2_id":"14796","normalized":[]},{"id":"14803","type":"CID","arg1_id":"14790","arg2_id":"14796","normalized":[]},{"id":"14804","type":"CID","arg1_id":"14792","arg2_id":"14796","normalized":[]},{"id":"14805","type":"CID","arg1_id":"14793","arg2_id":"14796","normalized":[]},{"id":"14806","type":"CID","arg1_id":"14798","arg2_id":"14796","normalized":[]},{"id":"14807","type":"CID","arg1_id":"14800","arg2_id":"14796","normalized":[]},{"id":"14808","type":"CID","arg1_id":"14787","arg2_id":"14795","normalized":[]},{"id":"14809","type":"CID","arg1_id":"14790","arg2_id":"14795","normalized":[]},{"id":"14810","type":"CID","arg1_id":"14792","arg2_id":"14795","normalized":[]},{"id":"14811","type":"CID","arg1_id":"14793","arg2_id":"14795","normalized":[]},{"id":"14812","type":"CID","arg1_id":"14798","arg2_id":"14795","normalized":[]},{"id":"14813","type":"CID","arg1_id":"14800","arg2_id":"14795","normalized":[]}]}
{"id":"14814","document_id":"12231232","passages":[{"id":"14815","type":"title","text":["The striatum as a target for anti-rigor effects of an antagonist of mGluR1, but not an agonist of group II metabotropic glutamate receptors."],"offsets":[[0,140]]},{"id":"14816","type":"abstract","text":["The aim of the present study was to find out whether the metabotropic receptor 1 (mGluR1) and group II mGluRs, localized in the striatum, are involved in antiparkinsonian-like effects in rats. Haloperidol (1 mg\/kg ip) induced parkinsonian-like muscle rigidity, measured as an increased resistance of a rat's hind foot to passive flexion and extension at the ankle joint. (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA; 0.5-15 microg\/0.5 microl), a potent and selective mGluR1 antagonist, or (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC; 7.5-15 microg\/0.5 microl), a selective group II agonist, was injected bilaterally into the striatum of haloperidol-treated animals. AIDA in doses of 7.5-15 microg\/0.5 microl diminished the haloperidol-induced muscle rigidity. In contrast, 2R,4R-APDC injections were ineffective. The present results may suggest that the blockade of striatal mGluR1, but not the stimulation of group II mGluRs, may ameliorate parkinsonian muscle rigidity."],"offsets":[[141,1126]]}],"entities":[{"id":"14817","type":"Chemical","text":["glutamate"],"offsets":[[120,129]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"14818","type":"Chemical","text":["Haloperidol"],"offsets":[[334,345]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"14819","type":"Disease","text":["parkinsonian"],"offsets":[[367,379]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"14820","type":"Disease","text":["muscle rigidity"],"offsets":[[385,400]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"14821","type":"Chemical","text":["(RS)-1-aminoindan-1,5-dicarboxylic acid"],"offsets":[[512,551]],"normalized":[{"db_name":"MESH","db_id":"C095756"}]},{"id":"14822","type":"Chemical","text":["AIDA"],"offsets":[[553,557]],"normalized":[{"db_name":"MESH","db_id":"C095756"}]},{"id":"14823","type":"Chemical","text":["(2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate"],"offsets":[[631,675]],"normalized":[{"db_name":"MESH","db_id":"C097299"}]},{"id":"14824","type":"Chemical","text":["2R,4R-APDC"],"offsets":[[677,687]],"normalized":[{"db_name":"MESH","db_id":"C097299"}]},{"id":"14825","type":"Chemical","text":["haloperidol"],"offsets":[[792,803]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"14826","type":"Chemical","text":["AIDA"],"offsets":[[821,825]],"normalized":[{"db_name":"MESH","db_id":"C095756"}]},{"id":"14827","type":"Chemical","text":["haloperidol"],"offsets":[[878,889]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"14828","type":"Disease","text":["muscle rigidity"],"offsets":[[898,913]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"14829","type":"Chemical","text":["2R,4R-APDC"],"offsets":[[928,938]],"normalized":[{"db_name":"MESH","db_id":"C097299"}]},{"id":"14830","type":"Disease","text":["parkinsonian"],"offsets":[[1097,1109]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"14831","type":"Disease","text":["muscle rigidity"],"offsets":[[1110,1125]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]}],"events":[],"coreferences":[],"relations":[{"id":"14832","type":"CID","arg1_id":"14818","arg2_id":"14820","normalized":[]},{"id":"14833","type":"CID","arg1_id":"14818","arg2_id":"14828","normalized":[]},{"id":"14834","type":"CID","arg1_id":"14818","arg2_id":"14831","normalized":[]},{"id":"14835","type":"CID","arg1_id":"14825","arg2_id":"14820","normalized":[]},{"id":"14836","type":"CID","arg1_id":"14825","arg2_id":"14828","normalized":[]},{"id":"14837","type":"CID","arg1_id":"14825","arg2_id":"14831","normalized":[]},{"id":"14838","type":"CID","arg1_id":"14827","arg2_id":"14820","normalized":[]},{"id":"14839","type":"CID","arg1_id":"14827","arg2_id":"14828","normalized":[]},{"id":"14840","type":"CID","arg1_id":"14827","arg2_id":"14831","normalized":[]}]}
{"id":"14841","document_id":"11847945","passages":[{"id":"14842","type":"title","text":["Acute cholestatic hepatitis after exposure to isoflurane."],"offsets":[[0,57]]},{"id":"14843","type":"abstract","text":["OBJECTIVE: To report a case of acute cholestatic hepatitis following exposure to the inhalational anesthetic isoflurane. CASE SUMMARY: A 70-year-old healthy woman from Iraq developed acute cholestatic hepatitis 3 weeks following repair of the right rotator cuff under general anesthesia. There was no evidence for viral, autoimmune, or metabolic causes of hepatitis. No other medications were involved except for dipyrone for analgesia. The alanine aminotransferase was elevated to a peak concentration of 1533 U\/L and the serum bilirubin reached a peak of 17.0 mg\/dL. There was slow improvement over 4 months. Accidental reexposure by the patient to dipyrone was uneventful. DISCUSSION: The clinical and histologic picture of this case resembles halothane hepatitis, which has a significant mortality rate. CONCLUSIONS: Isoflurane, a common anesthetic agent, can cause severe cholestatic hepatitis."],"offsets":[[58,957]]}],"entities":[{"id":"14844","type":"Disease","text":["cholestatic hepatitis"],"offsets":[[6,27]],"normalized":[{"db_name":"MESH","db_id":"D002779"},{"db_name":"MESH","db_id":"D056486"}]},{"id":"14845","type":"Disease","text":["cholestatic"],"offsets":[[6,17]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"14846","type":"Disease","text":["hepatitis"],"offsets":[[18,27]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"14847","type":"Chemical","text":["isoflurane"],"offsets":[[46,56]],"normalized":[{"db_name":"MESH","db_id":"D007530"}]},{"id":"14848","type":"Disease","text":["cholestatic hepatitis"],"offsets":[[95,116]],"normalized":[{"db_name":"MESH","db_id":"D002779"},{"db_name":"MESH","db_id":"D056486"}]},{"id":"14849","type":"Disease","text":["cholestatic"],"offsets":[[95,106]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"14850","type":"Disease","text":["hepatitis"],"offsets":[[107,116]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"14851","type":"Chemical","text":["isoflurane"],"offsets":[[167,177]],"normalized":[{"db_name":"MESH","db_id":"D007530"}]},{"id":"14852","type":"Disease","text":["cholestatic hepatitis"],"offsets":[[247,268]],"normalized":[{"db_name":"MESH","db_id":"D002779"},{"db_name":"MESH","db_id":"D056486"}]},{"id":"14853","type":"Disease","text":["cholestatic"],"offsets":[[247,258]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"14854","type":"Disease","text":["hepatitis"],"offsets":[[259,268]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"14855","type":"Disease","text":["hepatitis"],"offsets":[[414,423]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"14856","type":"Chemical","text":["dipyrone"],"offsets":[[471,479]],"normalized":[{"db_name":"MESH","db_id":"D004177"}]},{"id":"14857","type":"Disease","text":["analgesia"],"offsets":[[484,493]],"normalized":[{"db_name":"MESH","db_id":"D000699"}]},{"id":"14858","type":"Chemical","text":["alanine"],"offsets":[[499,506]],"normalized":[{"db_name":"MESH","db_id":"D000409"}]},{"id":"14859","type":"Chemical","text":["bilirubin"],"offsets":[[587,596]],"normalized":[{"db_name":"MESH","db_id":"D001663"}]},{"id":"14860","type":"Chemical","text":["dipyrone"],"offsets":[[709,717]],"normalized":[{"db_name":"MESH","db_id":"D004177"}]},{"id":"14861","type":"Disease","text":["halothane hepatitis"],"offsets":[[805,824]],"normalized":[{"db_name":"MESH","db_id":"C562477"}]},{"id":"14862","type":"Chemical","text":["Isoflurane"],"offsets":[[879,889]],"normalized":[{"db_name":"MESH","db_id":"D007530"}]},{"id":"14863","type":"Disease","text":["cholestatic hepatitis"],"offsets":[[935,956]],"normalized":[{"db_name":"MESH","db_id":"D002779"},{"db_name":"MESH","db_id":"D056486"}]},{"id":"14864","type":"Disease","text":["cholestatic"],"offsets":[[935,946]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"14865","type":"Disease","text":["hepatitis"],"offsets":[[947,956]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]}],"events":[],"coreferences":[],"relations":[{"id":"14866","type":"CID","arg1_id":"14847","arg2_id":"14844","normalized":[]},{"id":"14867","type":"CID","arg1_id":"14847","arg2_id":"14846","normalized":[]},{"id":"14868","type":"CID","arg1_id":"14847","arg2_id":"14848","normalized":[]},{"id":"14869","type":"CID","arg1_id":"14847","arg2_id":"14850","normalized":[]},{"id":"14870","type":"CID","arg1_id":"14847","arg2_id":"14852","normalized":[]},{"id":"14871","type":"CID","arg1_id":"14847","arg2_id":"14854","normalized":[]},{"id":"14872","type":"CID","arg1_id":"14847","arg2_id":"14855","normalized":[]},{"id":"14873","type":"CID","arg1_id":"14847","arg2_id":"14863","normalized":[]},{"id":"14874","type":"CID","arg1_id":"14847","arg2_id":"14865","normalized":[]},{"id":"14875","type":"CID","arg1_id":"14851","arg2_id":"14844","normalized":[]},{"id":"14876","type":"CID","arg1_id":"14851","arg2_id":"14846","normalized":[]},{"id":"14877","type":"CID","arg1_id":"14851","arg2_id":"14848","normalized":[]},{"id":"14878","type":"CID","arg1_id":"14851","arg2_id":"14850","normalized":[]},{"id":"14879","type":"CID","arg1_id":"14851","arg2_id":"14852","normalized":[]},{"id":"14880","type":"CID","arg1_id":"14851","arg2_id":"14854","normalized":[]},{"id":"14881","type":"CID","arg1_id":"14851","arg2_id":"14855","normalized":[]},{"id":"14882","type":"CID","arg1_id":"14851","arg2_id":"14863","normalized":[]},{"id":"14883","type":"CID","arg1_id":"14851","arg2_id":"14865","normalized":[]},{"id":"14884","type":"CID","arg1_id":"14862","arg2_id":"14844","normalized":[]},{"id":"14885","type":"CID","arg1_id":"14862","arg2_id":"14846","normalized":[]},{"id":"14886","type":"CID","arg1_id":"14862","arg2_id":"14848","normalized":[]},{"id":"14887","type":"CID","arg1_id":"14862","arg2_id":"14850","normalized":[]},{"id":"14888","type":"CID","arg1_id":"14862","arg2_id":"14852","normalized":[]},{"id":"14889","type":"CID","arg1_id":"14862","arg2_id":"14854","normalized":[]},{"id":"14890","type":"CID","arg1_id":"14862","arg2_id":"14855","normalized":[]},{"id":"14891","type":"CID","arg1_id":"14862","arg2_id":"14863","normalized":[]},{"id":"14892","type":"CID","arg1_id":"14862","arg2_id":"14865","normalized":[]},{"id":"14893","type":"CID","arg1_id":"14847","arg2_id":"14844","normalized":[]},{"id":"14894","type":"CID","arg1_id":"14847","arg2_id":"14845","normalized":[]},{"id":"14895","type":"CID","arg1_id":"14847","arg2_id":"14848","normalized":[]},{"id":"14896","type":"CID","arg1_id":"14847","arg2_id":"14849","normalized":[]},{"id":"14897","type":"CID","arg1_id":"14847","arg2_id":"14852","normalized":[]},{"id":"14898","type":"CID","arg1_id":"14847","arg2_id":"14853","normalized":[]},{"id":"14899","type":"CID","arg1_id":"14847","arg2_id":"14863","normalized":[]},{"id":"14900","type":"CID","arg1_id":"14847","arg2_id":"14864","normalized":[]},{"id":"14901","type":"CID","arg1_id":"14851","arg2_id":"14844","normalized":[]},{"id":"14902","type":"CID","arg1_id":"14851","arg2_id":"14845","normalized":[]},{"id":"14903","type":"CID","arg1_id":"14851","arg2_id":"14848","normalized":[]},{"id":"14904","type":"CID","arg1_id":"14851","arg2_id":"14849","normalized":[]},{"id":"14905","type":"CID","arg1_id":"14851","arg2_id":"14852","normalized":[]},{"id":"14906","type":"CID","arg1_id":"14851","arg2_id":"14853","normalized":[]},{"id":"14907","type":"CID","arg1_id":"14851","arg2_id":"14863","normalized":[]},{"id":"14908","type":"CID","arg1_id":"14851","arg2_id":"14864","normalized":[]},{"id":"14909","type":"CID","arg1_id":"14862","arg2_id":"14844","normalized":[]},{"id":"14910","type":"CID","arg1_id":"14862","arg2_id":"14845","normalized":[]},{"id":"14911","type":"CID","arg1_id":"14862","arg2_id":"14848","normalized":[]},{"id":"14912","type":"CID","arg1_id":"14862","arg2_id":"14849","normalized":[]},{"id":"14913","type":"CID","arg1_id":"14862","arg2_id":"14852","normalized":[]},{"id":"14914","type":"CID","arg1_id":"14862","arg2_id":"14853","normalized":[]},{"id":"14915","type":"CID","arg1_id":"14862","arg2_id":"14863","normalized":[]},{"id":"14916","type":"CID","arg1_id":"14862","arg2_id":"14864","normalized":[]}]}
{"id":"14917","document_id":"11284996","passages":[{"id":"14918","type":"title","text":["Calcitonin gene-related peptide levels during nitric oxide-induced headache in patients with chronic tension-type headache."],"offsets":[[0,123]]},{"id":"14919","type":"abstract","text":["It has been proposed that nitric oxide (NO) induced headache in primary headaches may be associated with release of calcitonin gene-related peptide (CGRP). In the present study we aimed to investigate plasma levels of CGRP during headache induced by the NO donor glyceryl trinitrate (GTN) in 16 patients with chronic tension-type headache and 16 healthy controls. The subjects were randomly allocated to receive 0.5 microg\/kg\/min GTN or placebo over 20 min on two headache-free days. Blood samples were collected at baseline, 10, 20 and 60 min after start of infusion. Both patients and controls developed significantly stronger immediate headache on the GTN day than on the placebo day and the headache was significantly more pronounced in patients than in controls. There was no difference between the area under the CGRP curve (AUCCGRP) on GTN vs. placebo day in either patients (P=0.65) or controls (P=0.48). The AUCCGRP recorded on the GTN day did not differ between patients and controls (P=0.36). Both in patients and controls, CGRP levels changed significantly over time, on both the GTN and placebo days (P < 0.05). The present study indicates that NO-induced immediate headache is not associated with release of CGRP."],"offsets":[[124,1351]]}],"entities":[{"id":"14920","type":"Chemical","text":["nitric oxide"],"offsets":[[46,58]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"14921","type":"Disease","text":["headache"],"offsets":[[67,75]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"14922","type":"Disease","text":["tension-type headache"],"offsets":[[101,122]],"normalized":[{"db_name":"MESH","db_id":"D018781"}]},{"id":"14923","type":"Chemical","text":["nitric oxide"],"offsets":[[150,162]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"14924","type":"Chemical","text":["NO"],"offsets":[[164,166]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"14925","type":"Disease","text":["headache"],"offsets":[[176,184]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"14926","type":"Disease","text":["primary 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{"id":"15026","document_id":"11078231","passages":[{"id":"15027","type":"title","text":["Myocardial ischemia due to coronary artery spasm during dobutamine stress echocardiography."],"offsets":[[0,91]]},{"id":"15028","type":"abstract","text":["Dobutamine stress echocardiography (DSE) is a useful and safe provocation test for myocardial ischemia. Until now, the test has been focused only on the organic lesion in the coronary artery, and positive DSE has indicated the presence of significant fixed coronary artery stenosis. The aim of the present study is to examine whether myocardial ischemia due to coronary spasm is induced by dobutamine. We performed DSE on 51 patients with coronary spastic angina but without significant fixed coronary artery stenosis. All patients had anginal attacks at rest with ST elevation on the electrocardiogram (variant angina). Coronary spasm was induced by intracoronary injection of acetylcholine, and no fixed coronary artery stenosis was documented on angiograms in all patients. DSE was performed with intravenous dobutamine infusion with an incremental doses of 5, 10, 20, 30, and 40 microg\/kg\/min every 5 minutes. Of the 51 patients, 7 patients showed asynergy with ST elevation. All 7 patients (13.7%) had chest pain during asynergy, and both chest pain and electrocardiographic changes were preceded by asynergy. These findings indicate that dobutamine can provoke coronary spasm in some patients with coronary spastic angina. When DSE is performed to evaluate coronary artery disease, not only fixed coronary stenosis, but also coronary spasm should be considered as a genesis of asynergy."],"offsets":[[92,1484]]}],"entities":[{"id":"15029","type":"Disease","text":["Myocardial ischemia"],"offsets":[[0,19]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"15030","type":"Disease","text":["coronary artery spasm"],"offsets":[[27,48]],"normalized":[{"db_name":"MESH","db_id":"D003329"}]},{"id":"15031","type":"Chemical","text":["dobutamine"],"offsets":[[56,66]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"15032","type":"Chemical","text":["Dobutamine"],"offsets":[[92,102]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"15033","type":"Disease","text":["myocardial ischemia"],"offsets":[[175,194]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"15034","type":"Disease","text":["coronary artery 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spasm"],"offsets":[[1259,1273]],"normalized":[{"db_name":"MESH","db_id":"D003329"}]},{"id":"15049","type":"Disease","text":["coronary spastic angina"],"offsets":[[1296,1319]],"normalized":[{"db_name":"MESH","db_id":"D000788"}]},{"id":"15050","type":"Disease","text":["coronary artery disease"],"offsets":[[1355,1378]],"normalized":[{"db_name":"MESH","db_id":"D003324"}]},{"id":"15051","type":"Disease","text":["coronary stenosis"],"offsets":[[1395,1412]],"normalized":[{"db_name":"MESH","db_id":"D023921"}]},{"id":"15052","type":"Disease","text":["coronary spasm"],"offsets":[[1423,1437]],"normalized":[{"db_name":"MESH","db_id":"D003329"}]}],"events":[],"coreferences":[],"relations":[{"id":"15053","type":"CID","arg1_id":"15031","arg2_id":"15038","normalized":[]},{"id":"15054","type":"CID","arg1_id":"15031","arg2_id":"15041","normalized":[]},{"id":"15055","type":"CID","arg1_id":"15031","arg2_id":"15049","normalized":[]},{"id":"15056","type":"CID","arg1_id":"15032","arg2_id":"15038","normalized":[]},{"id":"15057","type":"CID","arg1_id":"15032","arg2_id":"15041","normalized":[]},{"id":"15058","type":"CID","arg1_id":"15032","arg2_id":"15049","normalized":[]},{"id":"15059","type":"CID","arg1_id":"15037","arg2_id":"15038","normalized":[]},{"id":"15060","type":"CID","arg1_id":"15037","arg2_id":"15041","normalized":[]},{"id":"15061","type":"CID","arg1_id":"15037","arg2_id":"15049","normalized":[]},{"id":"15062","type":"CID","arg1_id":"15044","arg2_id":"15038","normalized":[]},{"id":"15063","type":"CID","arg1_id":"15044","arg2_id":"15041","normalized":[]},{"id":"15064","type":"CID","arg1_id":"15044","arg2_id":"15049","normalized":[]},{"id":"15065","type":"CID","arg1_id":"15047","arg2_id":"15038","normalized":[]},{"id":"15066","type":"CID","arg1_id":"15047","arg2_id":"15041","normalized":[]},{"id":"15067","type":"CID","arg1_id":"15047","arg2_id":"15049","normalized":[]},{"id":"15068","type":"CID","arg1_id":"15031","arg2_id":"15030","normalized":[]},{"id":"15069","type":"CID","arg1_id":"15031","arg2_id":"15036","normalized":[]},{"id":"15070","type":"CID","arg1_id":"15031","arg2_id":"15048","normalized":[]},{"id":"15071","type":"CID","arg1_id":"15031","arg2_id":"15052","normalized":[]},{"id":"15072","type":"CID","arg1_id":"15032","arg2_id":"15030","normalized":[]},{"id":"15073","type":"CID","arg1_id":"15032","arg2_id":"15036","normalized":[]},{"id":"15074","type":"CID","arg1_id":"15032","arg2_id":"15048","normalized":[]},{"id":"15075","type":"CID","arg1_id":"15032","arg2_id":"15052","normalized":[]},{"id":"15076","type":"CID","arg1_id":"15037","arg2_id":"15030","normalized":[]},{"id":"15077","type":"CID","arg1_id":"15037","arg2_id":"15036","normalized":[]},{"id":"15078","type":"CID","arg1_id":"15037","arg2_id":"15048","normalized":[]},{"id":"15079","type":"CID","arg1_id":"15037","arg2_id":"15052","normalized":[]},{"id":"15080","type":"CID","arg1_id":"15044","arg2_id":"15030","normalized":[]},{"id":"15081","type":"CID","arg1_id":"15044","arg2_id":"15036","normalized":[]},{"id":"15082","type":"CID","arg1_id":"15044","arg2_id":"15048","normalized":[]},{"id":"15083","type":"CID","arg1_id":"15044","arg2_id":"15052","normalized":[]},{"id":"15084","type":"CID","arg1_id":"15047","arg2_id":"15030","normalized":[]},{"id":"15085","type":"CID","arg1_id":"15047","arg2_id":"15036","normalized":[]},{"id":"15086","type":"CID","arg1_id":"15047","arg2_id":"15048","normalized":[]},{"id":"15087","type":"CID","arg1_id":"15047","arg2_id":"15052","normalized":[]}]}
{"id":"15088","document_id":"10523326","passages":[{"id":"15089","type":"title","text":["Nitric oxide synthase expression in the course of lead-induced hypertension."],"offsets":[[0,76]]},{"id":"15090","type":"abstract","text":["We recently showed elevated reactive oxygen species (ROS), reduced urinary excretion of NO metabolites (NOx), and increased NO sequestration as nitrotyrosine in various tissues in rats with lead-induced hypertension. This study was designed to discern whether the reduction in urinary NOx in lead-induced hypertension is, in part, due to depressed NO synthase (NOS) expression. Male Sprague-Dawley rats were randomly assigned to a lead-treated group (given lead acetate, 100 ppm, in drinking water and regular rat chow), a group given lead and vitamin E-fortified chow, or a normal control group given either regular food and water or vitamin E-fortified food for 12 weeks. Tail blood pressure, urinary NOx excretion, plasma malondialdehyde (MDA), and endothelial and inducible NOS (eNOS and iNOS) isotypes in the aorta and kidney were measured. The lead-treated group exhibited a rise in blood pressure and plasma MDA concentration, a fall in urinary NOx excretion, and a paradoxical rise in vascular and renal tissue eNOS and iNOS expression. Vitamin E supplementation ameliorated hypertension, lowered plasma MDA concentration, and raised urinary NOx excretion while significantly lowering vascular, but not renal, tissue eNOS and iNOS expression. Vitamin E supplementation had no effect on either blood pressure, plasma MDA, or NOS expression in the control group. The study also revealed significant inhibition of NOS enzymatic activity by lead in cell-free preparations. In conclusion, lead-induced hypertension in this model was associated with a compensatory upregulation of renal and vascular eNOS and iNOS expression. This is, in part, due to ROS-mediated NO inactivation, lead-associated inhibition of NOS activity, and perhaps stimulatory actions of increased shear stress associated with hypertension."],"offsets":[[77,1891]]}],"entities":[{"id":"15091","type":"Chemical","text":["Nitric oxide"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"15092","type":"Chemical","text":["lead"],"offsets":[[50,54]],"normalized":[{"db_name":"MESH","db_id":"D007854"}]},{"id":"15093","type":"Disease","text":["hypertension"],"offsets":[[63,75]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"15094","type":"Chemical","text":["oxygen"],"offsets":[[114,120]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"15095","type":"Chemical","text":["NO"],"offsets":[[165,167]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"15096","type":"Chemical","text":["NO"],"offsets":[[201,203]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"15097","type":"Chemical","text":["nitrotyrosine"],"offsets":[[221,234]],"normalized":[{"db_name":"MESH","db_id":"C002744"}]},{"id":"15098","type":"Chemical","text":["lead"],"offsets":[[267,271]],"normalized":[{"db_name":"MESH","db_id":"D007854"}]},{"id":"15099","type":"Disease","text":["hypertension"],"offsets":[[280,292]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"15100","type":"Chemical","text":["lead"],"offsets":[[369,373]],"normalized":[{"db_name":"MESH","db_id":"D007854"}]},{"id":"15101","type":"Disease","text":["hypertension"],"offsets":[[382,394]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"15102","type":"Chemical","text":["NO"],"offsets":[[425,427]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"15103","type":"Chemical","text":["lead"],"offsets":[[508,512]],"normalized":[{"db_name":"MESH","db_id":"D007854"}]},{"id":"15104","type":"Chemical","text":["lead acetate"],"offsets":[[534,546]],"normalized":[{"db_name":"MESH","db_id":"C008261"}]},{"id":"15105","type":"Chemical","text":["lead"],"offsets":[[612,616]],"normalized":[{"db_name":"MESH","db_id":"D007854"}]},{"id":"15106","type":"Chemical","text":["vitamin E"],"offsets":[[621,630]],"normalized":[{"db_name":"MESH","db_id":"D014810"}]},{"id":"15107","type":"Chemical","text":["vitamin E"],"offsets":[[712,721]],"normalized":[{"db_name":"MESH","db_id":"D014810"}]},{"id":"15108","type":"Chemical","text":["malondialdehyde"],"offsets":[[802,817]],"normalized":[{"db_name":"MESH","db_id":"D008315"}]},{"id":"15109","type":"Chemical","text":["MDA"],"offsets":[[819,822]],"normalized":[{"db_name":"MESH","db_id":"D008315"}]},{"id":"15110","type":"Chemical","text":["lead"],"offsets":[[927,931]],"normalized":[{"db_name":"MESH","db_id":"D007854"}]},{"id":"15111","type":"Chemical","text":["MDA"],"offsets":[[992,995]],"normalized":[{"db_name":"MESH","db_id":"D008315"}]},{"id":"15112","type":"Chemical","text":["Vitamin 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E"],"offsets":[[1328,1337]],"normalized":[{"db_name":"MESH","db_id":"D014810"}]},{"id":"15116","type":"Chemical","text":["MDA"],"offsets":[[1401,1404]],"normalized":[{"db_name":"MESH","db_id":"D008315"}]},{"id":"15117","type":"Chemical","text":["lead"],"offsets":[[1522,1526]],"normalized":[{"db_name":"MESH","db_id":"D007854"}]},{"id":"15118","type":"Chemical","text":["lead"],"offsets":[[1569,1573]],"normalized":[{"db_name":"MESH","db_id":"D007854"}]},{"id":"15119","type":"Disease","text":["hypertension"],"offsets":[[1582,1594]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"15120","type":"Chemical","text":["NO"],"offsets":[[1743,1745]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"15121","type":"Chemical","text":["lead"],"offsets":[[1760,1764]],"normalized":[{"db_name":"MESH","db_id":"D007854"}]},{"id":"15122","type":"Disease","text":["hypertension"],"offsets":[[1878,1890]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]}],"events":[],"coreferences":[],"relations":[{"id":"15123","type":"CID","arg1_id":"15092","arg2_id":"15093","normalized":[]},{"id":"15124","type":"CID","arg1_id":"15092","arg2_id":"15099","normalized":[]},{"id":"15125","type":"CID","arg1_id":"15092","arg2_id":"15101","normalized":[]},{"id":"15126","type":"CID","arg1_id":"15092","arg2_id":"15113","normalized":[]},{"id":"15127","type":"CID","arg1_id":"15092","arg2_id":"15119","normalized":[]},{"id":"15128","type":"CID","arg1_id":"15092","arg2_id":"15122","normalized":[]},{"id":"15129","type":"CID","arg1_id":"15098","arg2_id":"15093","normalized":[]},{"id":"15130","type":"CID","arg1_id":"15098","arg2_id":"15099","normalized":[]},{"id":"15131","type":"CID","arg1_id":"15098","arg2_id":"15101","normalized":[]},{"id":"15132","type":"CID","arg1_id":"15098","arg2_id":"15113","normalized":[]},{"id":"15133","type":"CID","arg1_id":"15098","arg2_id":"15119","normalized":[]},{"id":"15134","type":"CID","arg1_id":"15098","arg2_id":"15122","normalized":[]},{"id":"15135","type":"CID","arg1_id":"15100","arg2_id":"15093","normalized":[]},{"id":"15136","type":"CID","arg1_id":"15100","arg2_id":"15099","normalized":[]},{"id":"15137","type":"CID","arg1_id":"15100","arg2_id":"15101","normalized":[]},{"id":"15138","type":"CID","arg1_id":"15100","arg2_id":"15113","normalized":[]},{"id":"15139","type":"CID","arg1_id":"15100","arg2_id":"15119","normalized":[]},{"id":"15140","type":"CID","arg1_id":"15100","arg2_id":"15122","normalized":[]},{"id":"15141","type":"CID","arg1_id":"15103","arg2_id":"15093","normalized":[]},{"id":"15142","type":"CID","arg1_id":"15103","arg2_id":"15099","normalized":[]},{"id":"15143","type":"CID","arg1_id":"15103","arg2_id":"15101","normalized":[]},{"id":"15144","type":"CID","arg1_id":"15103","arg2_id":"15113","normalized":[]},{"id":"15145","type":"CID","arg1_id":"15103","arg2_id":"15119","normalized":[]},{"id":"15146","type":"CID","arg1_id":"15103","arg2_id":"15122","normalized":[]},{"id":"15147","type":"CID","arg1_id":"15105","arg2_id":"15093","normalized":[]},{"id":"15148","type":"CID","arg1_id":"15105","arg2_id":"15099","normalized":[]},{"id":"15149","type":"CID","arg1_id":"15105","arg2_id":"15101","normalized":[]},{"id":"15150","type":"CID","arg1_id":"15105","arg2_id":"15113","normalized":[]},{"id":"15151","type":"CID","arg1_id":"15105","arg2_id":"15119","normalized":[]},{"id":"15152","type":"CID","arg1_id":"15105","arg2_id":"15122","normalized":[]},{"id":"15153","type":"CID","arg1_id":"15110","arg2_id":"15093","normalized":[]},{"id":"15154","type":"CID","arg1_id":"15110","arg2_id":"15099","normalized":[]},{"id":"15155","type":"CID","arg1_id":"15110","arg2_id":"15101","normalized":[]},{"id":"15156","type":"CID","arg1_id":"15110","arg2_id":"15113","normalized":[]},{"id":"15157","type":"CID","arg1_id":"15110","arg2_id":"15119","normalized":[]},{"id":"15158","type":"CID","arg1_id":"15110","arg2_id":"15122","normalized":[]},{"id":"15159","type":"CID","arg1_id":"15117","arg2_id":"15093","normalized":[]},{"id":"15160","type":"CID","arg1_id":"15117","arg2_id":"15099","normalized":[]},{"id":"15161","type":"CID","arg1_id":"15117","arg2_id":"15101","normalized":[]},{"id":"15162","type":"CID","arg1_id":"15117","arg2_id":"15113","normalized":[]},{"id":"15163","type":"CID","arg1_id":"15117","arg2_id":"15119","normalized":[]},{"id":"15164","type":"CID","arg1_id":"15117","arg2_id":"15122","normalized":[]},{"id":"15165","type":"CID","arg1_id":"15118","arg2_id":"15093","normalized":[]},{"id":"15166","type":"CID","arg1_id":"15118","arg2_id":"15099","normalized":[]},{"id":"15167","type":"CID","arg1_id":"15118","arg2_id":"15101","normalized":[]},{"id":"15168","type":"CID","arg1_id":"15118","arg2_id":"15113","normalized":[]},{"id":"15169","type":"CID","arg1_id":"15118","arg2_id":"15119","normalized":[]},{"id":"15170","type":"CID","arg1_id":"15118","arg2_id":"15122","normalized":[]},{"id":"15171","type":"CID","arg1_id":"15121","arg2_id":"15093","normalized":[]},{"id":"15172","type":"CID","arg1_id":"15121","arg2_id":"15099","normalized":[]},{"id":"15173","type":"CID","arg1_id":"15121","arg2_id":"15101","normalized":[]},{"id":"15174","type":"CID","arg1_id":"15121","arg2_id":"15113","normalized":[]},{"id":"15175","type":"CID","arg1_id":"15121","arg2_id":"15119","normalized":[]},{"id":"15176","type":"CID","arg1_id":"15121","arg2_id":"15122","normalized":[]}]}
{"id":"15177","document_id":"9867728","passages":[{"id":"15178","type":"title","text":["Risk for valvular heart disease among users of fenfluramine and dexfenfluramine who underwent echocardiography before use of medication."],"offsets":[[0,136]]},{"id":"15179","type":"abstract","text":["BACKGROUND: Because uncontrolled echocardiographic surveys suggested that up to 30% to 38% of users of fenfluramine and dexfenfluramine had valvular disease, these drugs were withdrawn from the market. OBJECTIVE: To determine the risk for new or worsening valvular abnormalities among users of fenfluramine or dexfenfluramine who underwent echocardiography before they began to take these medications. DESIGN: Cohort study. SETTING: Academic primary care practices. PATIENTS: 46 patients who used fenfluramine or dexfenfluramine for 14 days or more and had echocardiograms obtained before therapy. MEASUREMENTS: Follow-up echocardiography. The primary outcome was new or worsening valvulopathy, defined as progression of either aortic or mitral regurgitation by at least one degree of severity and disease that met U.S. Food and Drug Administration criteria (at least mild aortic regurgitation or moderate mitral regurgitation). RESULTS: Two patients (4.3% [95% CI, 0.6% to 14.8%]) receiving fenfluramine-phentermine developed valvular heart disease. One had baseline bicuspid aortic valve and mild aortic regurgitation that progressed to moderate regurgitation. The second patient developed new moderate aortic insufficiency. CONCLUSION: Users of diet medications are at risk for valvular heart disease. However, the incidence may be lower than that reported previously."],"offsets":[[137,1508]]}],"entities":[{"id":"15180","type":"Disease","text":["valvular heart disease"],"offsets":[[9,31]],"normalized":[{"db_name":"MESH","db_id":"D006349"}]},{"id":"15181","type":"Chemical","text":["fenfluramine"],"offsets":[[47,59]],"normalized":[{"db_name":"MESH","db_id":"D005277"}]},{"id":"15182","type":"Chemical","text":["dexfenfluramine"],"offsets":[[64,79]],"normalized":[{"db_name":"MESH","db_id":"D020372"}]},{"id":"15183","type":"Chemical","text":["fenfluramine"],"offsets":[[240,252]],"normalized":[{"db_name":"MESH","db_id":"D005277"}]},{"id":"15184","type":"Chemical","text":["dexfenfluramine"],"offsets":[[257,272]],"normalized":[{"db_name":"MESH","db_id":"D020372"}]},{"id":"15185","type":"Disease","text":["valvular disease"],"offsets":[[277,293]],"normalized":[{"db_name":"MESH","db_id":"D006349"}]},{"id":"15186","type":"Disease","text":["valvular abnormalities"],"offsets":[[393,415]],"normalized":[{"db_name":"MESH","db_id":"D006349"}]},{"id":"15187","type":"Chemical","text":["fenfluramine"],"offsets":[[431,443]],"normalized":[{"db_name":"MESH","db_id":"D005277"}]},{"id":"15188","type":"Chemical","text":["dexfenfluramine"],"offsets":[[447,462]],"normalized":[{"db_name":"MESH","db_id":"D020372"}]},{"id":"15189","type":"Chemical","text":["fenfluramine"],"offsets":[[634,646]],"normalized":[{"db_name":"MESH","db_id":"D005277"}]},{"id":"15190","type":"Chemical","text":["dexfenfluramine"],"offsets":[[650,665]],"normalized":[{"db_name":"MESH","db_id":"D020372"}]},{"id":"15191","type":"Disease","text":["valvulopathy"],"offsets":[[818,830]],"normalized":[{"db_name":"MESH","db_id":"D006349"}]},{"id":"15192","type":"Disease","text":["aortic or mitral regurgitation"],"offsets":[[865,895]],"normalized":[{"db_name":"MESH","db_id":"D001022"},{"db_name":"MESH","db_id":"D008944"}]},{"id":"15193","type":"Disease","text":["aortic","regurgitation"],"offsets":[[865,871],[882,895]],"normalized":[{"db_name":"MESH","db_id":"D001022"}]},{"id":"15194","type":"Disease","text":["mitral regurgitation"],"offsets":[[875,895]],"normalized":[{"db_name":"MESH","db_id":"D008944"}]},{"id":"15195","type":"Disease","text":["aortic regurgitation"],"offsets":[[1010,1030]],"normalized":[{"db_name":"MESH","db_id":"D001022"}]},{"id":"15196","type":"Disease","text":["mitral regurgitation"],"offsets":[[1043,1063]],"normalized":[{"db_name":"MESH","db_id":"D008944"}]},{"id":"15197","type":"Chemical","text":["fenfluramine"],"offsets":[[1129,1141]],"normalized":[{"db_name":"MESH","db_id":"D005277"}]},{"id":"15198","type":"Chemical","text":["phentermine"],"offsets":[[1142,1153]],"normalized":[{"db_name":"MESH","db_id":"D010645"}]},{"id":"15199","type":"Disease","text":["valvular heart disease"],"offsets":[[1164,1186]],"normalized":[{"db_name":"MESH","db_id":"D006349"}]},{"id":"15200","type":"Disease","text":["bicuspid aortic valve"],"offsets":[[1205,1226]],"normalized":[{"db_name":"MESH","db_id":"C562388"}]},{"id":"15201","type":"Disease","text":["aortic regurgitation"],"offsets":[[1236,1256]],"normalized":[{"db_name":"MESH","db_id":"D001022"}]},{"id":"15202","type":"Disease","text":["aortic insufficiency"],"offsets":[[1342,1362]],"normalized":[{"db_name":"MESH","db_id":"D001022"}]},{"id":"15203","type":"Disease","text":["valvular heart disease"],"offsets":[[1418,1440]],"normalized":[{"db_name":"MESH","db_id":"D006349"}]}],"events":[],"coreferences":[],"relations":[{"id":"15204","type":"CID","arg1_id":"15181","arg2_id":"15192","normalized":[]},{"id":"15205","type":"CID","arg1_id":"15181","arg2_id":"15193","normalized":[]},{"id":"15206","type":"CID","arg1_id":"15181","arg2_id":"15195","normalized":[]},{"id":"15207","type":"CID","arg1_id":"15181","arg2_id":"15201","normalized":[]},{"id":"15208","type":"CID","arg1_id":"15181","arg2_id":"15202","normalized":[]},{"id":"15209","type":"CID","arg1_id":"15183","arg2_id":"15192","normalized":[]},{"id":"15210","type":"CID","arg1_id":"15183","arg2_id":"15193","normalized":[]},{"id":"15211","type":"CID","arg1_id":"15183","arg2_id":"15195","normalized":[]},{"id":"15212","type":"CID","arg1_id":"15183","arg2_id":"15201","normalized":[]},{"id":"15213","type":"CID","arg1_id":"15183","arg2_id":"15202","normalized":[]},{"id":"15214","type":"CID","arg1_id":"15187","arg2_id":"15192","normalized":[]},{"id":"15215","type":"CID","arg1_id":"15187","arg2_id":"15193","normalized":[]},{"id":"15216","type":"CID","arg1_id":"15187","arg2_id":"15195","normalized":[]},{"id":"15217","type":"CID","arg1_id":"15187","arg2_id":"15201","normalized":[]},{"id":"15218","type":"CID","arg1_id":"15187","arg2_id":"15202","normalized":[]},{"id":"15219","type":"CID","arg1_id":"15189","arg2_id":"15192","normalized":[]},{"id":"15220","type":"CID","arg1_id":"15189","arg2_id":"15193","normalized":[]},{"id":"15221","type":"CID","arg1_id":"15189","arg2_id":"15195","normalized":[]},{"id":"15222","type":"CID","arg1_id":"15189","arg2_id":"15201","normalized":[]},{"id":"15223","type":"CID","arg1_id":"15189","arg2_id":"15202","normalized":[]},{"id":"15224","type":"CID","arg1_id":"15197","arg2_id":"15192","normalized":[]},{"id":"15225","type":"CID","arg1_id":"15197","arg2_id":"15193","normalized":[]},{"id":"15226","type":"CID","arg1_id":"15197","arg2_id":"15195","normalized":[]},{"id":"15227","type":"CID","arg1_id":"15197","arg2_id":"15201","normalized":[]},{"id":"15228","type":"CID","arg1_id":"15197","arg2_id":"15202","normalized":[]},{"id":"15229","type":"CID","arg1_id":"15198","arg2_id":"15192","normalized":[]},{"id":"15230","type":"CID","arg1_id":"15198","arg2_id":"15193","normalized":[]},{"id":"15231","type":"CID","arg1_id":"15198","arg2_id":"15195","normalized":[]},{"id":"15232","type":"CID","arg1_id":"15198","arg2_id":"15201","normalized":[]},{"id":"15233","type":"CID","arg1_id":"15198","arg2_id":"15202","normalized":[]}]}
{"id":"15234","document_id":"9636837","passages":[{"id":"15235","type":"title","text":["Carboplatin toxic effects on the peripheral nervous system of the rat."],"offsets":[[0,70]]},{"id":"15236","type":"abstract","text":["BACKGROUND: The most striking of carboplatin's advantages (CBDCA) over cisplatin (CDDP) is its markedly reduced rate of neurotoxic effects. However, the use of CBDCA higher-intensity schedules and the association with other neurotoxic drugs in polychemotherapy may cause some concern about its safety with respect to peripheral nervous system damage. MATERIALS AND METHODS: Two different schedules of CBDCA administration (10 mg\/kg and 15 mg\/kg i.p. twice a week for nine times) were evaluated in Wistar rats. Neurotoxicity was assessed for behavioral (tail-flick test), neurophysiological (nerve conduction velocity in the tail nerve), morphological, morphometrical and analytical effects. RESULTS: CBDCA administration induced dose-dependent peripheral neurotoxicity. Pain perception and nerve conduction velocity in the tail were significantly impaired, particularly after the high-dose treatment. The dorsal root ganglia sensory neurons and, to a lesser extent, satellite cells showed the same changes as those induced by CDDP, mainly affecting the nucleus and nucleolus of ganglionic sensory neurons. Moreover, significant amounts of platinum were detected in the dorsal root ganglia and kidney after CBDCA treatment. CONCLUSIONS: CBDCA is neurotoxic in our model, and the type of pathological changes it induces are so closely similar to those caused by CDDP that it is probable that neurotoxicity is induced in the two drugs by the same mechanism. This model can be used alone or in combination with other drugs to explore the effect of CBDCA on the peripheral nervous system."],"offsets":[[71,1654]]}],"entities":[{"id":"15237","type":"Chemical","text":["Carboplatin"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"15238","type":"Chemical","text":["carboplatin"],"offsets":[[104,115]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"15239","type":"Chemical","text":["CBDCA"],"offsets":[[130,135]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"15240","type":"Chemical","text":["cisplatin"],"offsets":[[142,151]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"15241","type":"Chemical","text":["CDDP"],"offsets":[[153,157]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"15242","type":"Disease","text":["neurotoxic"],"offsets":[[191,201]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"15243","type":"Chemical","text":["CBDCA"],"offsets":[[231,236]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"15244","type":"Disease","text":["neurotoxic"],"offsets":[[295,305]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"15245","type":"Disease","text":["peripheral nervous system damage"],"offsets":[[388,420]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"15246","type":"Chemical","text":["CBDCA"],"offsets":[[472,477]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"15247","type":"Disease","text":["Neurotoxicity"],"offsets":[[581,594]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"15248","type":"Chemical","text":["CBDCA"],"offsets":[[771,776]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"15249","type":"Disease","text":["peripheral neurotoxicity"],"offsets":[[815,839]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"15250","type":"Disease","text":["Pain"],"offsets":[[841,845]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"15251","type":"Chemical","text":["CDDP"],"offsets":[[1097,1101]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"15252","type":"Chemical","text":["platinum"],"offsets":[[1210,1218]],"normalized":[{"db_name":"MESH","db_id":"D010984"}]},{"id":"15253","type":"Chemical","text":["CBDCA"],"offsets":[[1277,1282]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"15254","type":"Chemical","text":["CBDCA"],"offsets":[[1307,1312]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"15255","type":"Disease","text":["neurotoxic"],"offsets":[[1316,1326]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"15256","type":"Chemical","text":["CDDP"],"offsets":[[1431,1435]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"15257","type":"Disease","text":["neurotoxicity"],"offsets":[[1461,1474]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"15258","type":"Chemical","text":["CBDCA"],"offsets":[[1615,1620]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]}],"events":[],"coreferences":[],"relations":[{"id":"15259","type":"CID","arg1_id":"15240","arg2_id":"15245","normalized":[]},{"id":"15260","type":"CID","arg1_id":"15240","arg2_id":"15249","normalized":[]},{"id":"15261","type":"CID","arg1_id":"15241","arg2_id":"15245","normalized":[]},{"id":"15262","type":"CID","arg1_id":"15241","arg2_id":"15249","normalized":[]},{"id":"15263","type":"CID","arg1_id":"15251","arg2_id":"15245","normalized":[]},{"id":"15264","type":"CID","arg1_id":"15251","arg2_id":"15249","normalized":[]},{"id":"15265","type":"CID","arg1_id":"15256","arg2_id":"15245","normalized":[]},{"id":"15266","type":"CID","arg1_id":"15256","arg2_id":"15249","normalized":[]},{"id":"15267","type":"CID","arg1_id":"15237","arg2_id":"15245","normalized":[]},{"id":"15268","type":"CID","arg1_id":"15237","arg2_id":"15249","normalized":[]},{"id":"15269","type":"CID","arg1_id":"15238","arg2_id":"15245","normalized":[]},{"id":"15270","type":"CID","arg1_id":"15238","arg2_id":"15249","normalized":[]},{"id":"15271","type":"CID","arg1_id":"15239","arg2_id":"15245","normalized":[]},{"id":"15272","type":"CID","arg1_id":"15239","arg2_id":"15249","normalized":[]},{"id":"15273","type":"CID","arg1_id":"15243","arg2_id":"15245","normalized":[]},{"id":"15274","type":"CID","arg1_id":"15243","arg2_id":"15249","normalized":[]},{"id":"15275","type":"CID","arg1_id":"15246","arg2_id":"15245","normalized":[]},{"id":"15276","type":"CID","arg1_id":"15246","arg2_id":"15249","normalized":[]},{"id":"15277","type":"CID","arg1_id":"15248","arg2_id":"15245","normalized":[]},{"id":"15278","type":"CID","arg1_id":"15248","arg2_id":"15249","normalized":[]},{"id":"15279","type":"CID","arg1_id":"15253","arg2_id":"15245","normalized":[]},{"id":"15280","type":"CID","arg1_id":"15253","arg2_id":"15249","normalized":[]},{"id":"15281","type":"CID","arg1_id":"15254","arg2_id":"15245","normalized":[]},{"id":"15282","type":"CID","arg1_id":"15254","arg2_id":"15249","normalized":[]},{"id":"15283","type":"CID","arg1_id":"15258","arg2_id":"15245","normalized":[]},{"id":"15284","type":"CID","arg1_id":"15258","arg2_id":"15249","normalized":[]}]}
{"id":"15285","document_id":"9579567","passages":[{"id":"15286","type":"title","text":["Iatrogenic risks of endometrial carcinoma after treatment for breast cancer in a large French case-control study. F  d  ration Nationale des Centres de Lutte Contre le Cancer (FNCLCC)."],"offsets":[[0,184]]},{"id":"15287","type":"abstract","text":["Since tamoxifen is widely used in breast cancer treatment and has been proposed for the prevention of breast cancer, its endometrial iatrogenic effects must be carefully examined. We have investigated the association between endometrial cancer and tamoxifen use or other treatments in women treated for breast cancer in a case-control study. Cases of endometrial cancer diagnosed after breast cancer (n = 135) and 467 controls matched for age, year of diagnosis of breast cancer and hospital and survival time with an intact uterus were included. Women who had received tamoxifen were significantly more likely to have endometrial cancer diagnosed than those who had not (crude relative risk = 4.9, p = 0.0001). Univariate and adjusted analyses showed that the risk increased with the length of treatment (p = 0.0001) or the cumulative dose of tamoxifen received (p = 0.0001), irrespective of the daily dose. Women who had undergone pelvic radiotherapy also had a higher risk (crude relative risk = 7.8, p = 0.0001). After adjusting for confounding factors, the risk was higher for tamoxifen users (p = 0.0012), treatment for more than 3 years (all p < 0.03) and pelvic radiotherapy (p = 0.012). Women who had endometrial cancer and had received tamoxifen had more advanced disease and poorer prognosis than those with endometrial cancer who had not received this treatment. Our results suggest a causal role of tamoxifen in endometrial cancer, particularly when used as currently proposed for breast cancer prevention. Pelvic radiotherapy may be an additional iatrogenic factor for women with breast cancer. Endometrial cancers diagnosed in women treated with tamoxifen have poorer prognosis. Women who receive tamoxifen for breast cancer should be offered gynaecological surveillance during and after treatment. A long-term evaluation of the risk-benefit ratio of tamoxifen as a preventive treatment for breast cancer is clearly warranted."],"offsets":[[185,2126]]}],"entities":[{"id":"15288","type":"Disease","text":["endometrial carcinoma"],"offsets":[[20,41]],"normalized":[{"db_name":"MESH","db_id":"D016889"}]},{"id":"15289","type":"Disease","text":["breast cancer"],"offsets":[[62,75]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"15290","type":"Chemical","text":["tamoxifen"],"offsets":[[191,200]],"normalized":[{"db_name":"MESH","db_id":"D013629"}]},{"id":"15291","type":"Disease","text":["breast cancer"],"offsets":[[219,232]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"15292","type":"Disease","text":["breast cancer"],"offsets":[[287,300]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"15293","type":"Disease","text":["endometrial 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{"id":"15397","document_id":"9205462","passages":[{"id":"15398","type":"title","text":["Granulosa cell tumor of the ovary associated with antecedent tamoxifen use."],"offsets":[[0,75]]},{"id":"15399","type":"abstract","text":["BACKGROUND: Increased attention has been focused recently on the estrogenic effects of tamoxifen. Review of the literature reveals an association between tamoxifen use and gynecologic tumors. CASE: A 52-year-old postmenopausal woman was treated with tamoxifen for stage II estrogen receptor-positive breast carcinoma. Her aspartate transaminase and alanine transaminase levels increase markedly after 6 months of tamoxifen use. After an additional 17 months of elevated serum transaminases, the patient was found to have a stage Ic granulosa cell tumor of the ovary. CONCLUSION: Patients with tamoxifen-induced liver dysfunction may be at increased risk for granulosa cell tumors because of alterations in tamoxifen metabolism."],"offsets":[[76,803]]}],"entities":[{"id":"15400","type":"Disease","text":["Granulosa cell tumor of the ovary"],"offsets":[[0,33]],"normalized":[{"db_name":"MESH","db_id":"C537296"}]},{"id":"15401","type":"Chemical","text":["tamoxifen"],"offsets":[[61,70]],"normalized":[{"db_name":"MESH","db_id":"D013629"}]},{"id":"15402","type":"Chemical","text":["tamoxifen"],"offsets":[[163,172]],"normalized":[{"db_name":"MESH","db_id":"D013629"}]},{"id":"15403","type":"Chemical","text":["tamoxifen"],"offsets":[[230,239]],"normalized":[{"db_name":"MESH","db_id":"D013629"}]},{"id":"15404","type":"Disease","text":["tumors"],"offsets":[[260,266]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"15405","type":"Chemical","text":["tamoxifen"],"offsets":[[326,335]],"normalized":[{"db_name":"MESH","db_id":"D013629"}]},{"id":"15406","type":"Chemical","text":["estrogen"],"offsets":[[349,357]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"15407","type":"Disease","text":["breast carcinoma"],"offsets":[[376,392]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"15408","type":"Chemical","text":["aspartate"],"offsets":[[398,407]],"normalized":[{"db_name":"MESH","db_id":"D001224"}]},{"id":"15409","type":"Chemical","text":["alanine"],"offsets":[[425,432]],"normalized":[{"db_name":"MESH","db_id":"D000409"}]},{"id":"15410","type":"Chemical","text":["tamoxifen"],"offsets":[[489,498]],"normalized":[{"db_name":"MESH","db_id":"D013629"}]},{"id":"15411","type":"Disease","text":["granulosa cell tumor of the ovary"],"offsets":[[608,641]],"normalized":[{"db_name":"MESH","db_id":"C537296"}]},{"id":"15412","type":"Chemical","text":["tamoxifen"],"offsets":[[669,678]],"normalized":[{"db_name":"MESH","db_id":"D013629"}]},{"id":"15413","type":"Disease","text":["liver dysfunction"],"offsets":[[687,704]],"normalized":[{"db_name":"MESH","db_id":"D017093"}]},{"id":"15414","type":"Disease","text":["granulosa cell tumors"],"offsets":[[734,755]],"normalized":[{"db_name":"MESH","db_id":"D006106"}]},{"id":"15415","type":"Chemical","text":["tamoxifen"],"offsets":[[782,791]],"normalized":[{"db_name":"MESH","db_id":"D013629"}]}],"events":[],"coreferences":[],"relations":[{"id":"15416","type":"CID","arg1_id":"15401","arg2_id":"15413","normalized":[]},{"id":"15417","type":"CID","arg1_id":"15402","arg2_id":"15413","normalized":[]},{"id":"15418","type":"CID","arg1_id":"15403","arg2_id":"15413","normalized":[]},{"id":"15419","type":"CID","arg1_id":"15405","arg2_id":"15413","normalized":[]},{"id":"15420","type":"CID","arg1_id":"15410","arg2_id":"15413","normalized":[]},{"id":"15421","type":"CID","arg1_id":"15412","arg2_id":"15413","normalized":[]},{"id":"15422","type":"CID","arg1_id":"15415","arg2_id":"15413","normalized":[]},{"id":"15423","type":"CID","arg1_id":"15401","arg2_id":"15400","normalized":[]},{"id":"15424","type":"CID","arg1_id":"15401","arg2_id":"15411","normalized":[]},{"id":"15425","type":"CID","arg1_id":"15402","arg2_id":"15400","normalized":[]},{"id":"15426","type":"CID","arg1_id":"15402","arg2_id":"15411","normalized":[]},{"id":"15427","type":"CID","arg1_id":"15403","arg2_id":"15400","normalized":[]},{"id":"15428","type":"CID","arg1_id":"15403","arg2_id":"15411","normalized":[]},{"id":"15429","type":"CID","arg1_id":"15405","arg2_id":"15400","normalized":[]},{"id":"15430","type":"CID","arg1_id":"15405","arg2_id":"15411","normalized":[]},{"id":"15431","type":"CID","arg1_id":"15410","arg2_id":"15400","normalized":[]},{"id":"15432","type":"CID","arg1_id":"15410","arg2_id":"15411","normalized":[]},{"id":"15433","type":"CID","arg1_id":"15412","arg2_id":"15400","normalized":[]},{"id":"15434","type":"CID","arg1_id":"15412","arg2_id":"15411","normalized":[]},{"id":"15435","type":"CID","arg1_id":"15415","arg2_id":"15400","normalized":[]},{"id":"15436","type":"CID","arg1_id":"15415","arg2_id":"15411","normalized":[]}]}
{"id":"15437","document_id":"9098464","passages":[{"id":"15438","type":"title","text":["A murine model of adenomyosis: the effects of hyperprolactinemia induced by fluoxetine hydrochloride, a selective serotonin reuptake inhibitor, on adenomyosis induction in Wistar albino rats."],"offsets":[[0,191]]},{"id":"15439","type":"abstract","text":["OBJECTIVE: The aim of this study was to investigate whether fluoxetine given to castrated and noncastrated rats caused hyperprolactinemia and its effects with respect to adenomyosis. DESIGN: Fluoxetine, a serotonin reuptake inhibitor, was given to Wistar Albino rats for 98 days to produce hyperprolactinemia. The drug was given to two groups consisting of castrated and noncastrated rats and compared to two groups of castrated and noncastrated controls. Prolactin levels were measured and the uteri of the rats were removed for histopathological analysis at the end of 98 days. SETTING: Marmara University School of Medicine, Department of Histology and Embryology, Zeynep Kamil Women and Children's Hospital. MAIN OUTCOME MEASURES: Serum prolactin levels, uterine histopathology. RESULTS: The prolactin levels of castrated and noncastrated groups treated with fluoxetine were statistically significantly higher when compared to their respective control groups. Histological studies revealed 11 cases of adenomyosis, all within the noncastrated group receiving fluoxetine. CONCLUSION: It was suggested that high serum prolactin levels cause degeneration of myometrial cells in the presence of ovarian steroids that results in a myometrial invasion by endometrial stroma. This invasion eventually progresses to adenomyosis."],"offsets":[[192,1516]]}],"entities":[{"id":"15440","type":"Disease","text":["adenomyosis"],"offsets":[[18,29]],"normalized":[{"db_name":"MESH","db_id":"D062788"}]},{"id":"15441","type":"Disease","text":["hyperprolactinemia"],"offsets":[[46,64]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"15442","type":"Chemical","text":["fluoxetine 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{"id":"15496","document_id":"8424298","passages":[{"id":"15497","type":"title","text":["Effects of deliberate hypotension induced by labetalol with isoflurane on neuropsychological function."],"offsets":[[0,102]]},{"id":"15498","type":"abstract","text":["The effect of deliberate hypotension on brain function measured by neuropsychological tests was studied in 41 adult patients. Twenty-four patients were anaesthetized for middle-ear surgery with deliberate hypotension induced by labetalol with isoflurane (hypotensive group). Seventeen patients without hypotension served as a control group. The mean arterial pressure was 77 +\/- 2 mmHg (10.3 +\/- 0.3 kPa) before hypotension and 50 +\/- 0 mmHg (6.7 +\/- 0.0 kPa) during hypotension in the hypotensive group, and 86 +\/- 2 mmHg (11.5 +\/- 0.3 kPa) during anaesthesia in the control group. The following psychological tests were performed: four subtests of the Wechsler Adult Intelligence Scale (similarities, digit span, vocabulary and digit symbol), Trail-Making tests A and B, Zung tests (self-rating anxiety scale and self-rating depression scale) and two-part memory test battery with immediate and delayed recall. The tests were performed preoperatively and 2 days postoperatively. There were no statistically significant differences between the groups in any of the tests in the changes from preoperative value to postoperative value. The results indicate that hypotension induced by labetalol with isoflurane has no significant harmful effects on mental functions compared to normotensive anaesthesia."],"offsets":[[103,1405]]}],"entities":[{"id":"15499","type":"Disease","text":["hypotension"],"offsets":[[22,33]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"15500","type":"Chemical","text":["labetalol"],"offsets":[[45,54]],"normalized":[{"db_name":"MESH","db_id":"D007741"}]},{"id":"15501","type":"Chemical","text":["isoflurane"],"offsets":[[60,70]],"normalized":[{"db_name":"MESH","db_id":"D007530"}]},{"id":"15502","type":"Disease","text":["hypotension"],"offsets":[[128,139]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"15503","type":"Disease","text":["hypotension"],"offsets":[[308,319]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"15504","type":"Chemical","text":["labetalol"],"offsets":[[331,340]],"normalized":[{"db_name":"MESH","db_id":"D007741"}]},{"id":"15505","type":"Chemical","text":["isoflurane"],"offsets":[[346,356]],"normalized":[{"db_name":"MESH","db_id":"D007530"}]},{"id":"15506","type":"Disease","text":["hypotensive"],"offsets":[[358,369]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"15507","type":"Disease","text":["hypotension"],"offsets":[[405,416]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"15508","type":"Disease","text":["hypotension"],"offsets":[[515,526]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"15509","type":"Disease","text":["hypotension"],"offsets":[[570,581]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"15510","type":"Disease","text":["hypotensive"],"offsets":[[589,600]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"15511","type":"Disease","text":["anxiety"],"offsets":[[900,907]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"15512","type":"Disease","text":["depression"],"offsets":[[930,940]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"15513","type":"Disease","text":["hypotension"],"offsets":[[1264,1275]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"15514","type":"Chemical","text":["labetalol"],"offsets":[[1287,1296]],"normalized":[{"db_name":"MESH","db_id":"D007741"}]},{"id":"15515","type":"Chemical","text":["isoflurane"],"offsets":[[1302,1312]],"normalized":[{"db_name":"MESH","db_id":"D007530"}]}],"events":[],"coreferences":[],"relations":[{"id":"15516","type":"CID","arg1_id":"15500","arg2_id":"15499","normalized":[]},{"id":"15517","type":"CID","arg1_id":"15500","arg2_id":"15502","normalized":[]},{"id":"15518","type":"CID","arg1_id":"15500","arg2_id":"15503","normalized":[]},{"id":"15519","type":"CID","arg1_id":"15500","arg2_id":"15506","normalized":[]},{"id":"15520","type":"CID","arg1_id":"15500","arg2_id":"15507","normalized":[]},{"id":"15521","type":"CID","arg1_id":"15500","arg2_id":"15508","normalized":[]},{"id":"15522","type":"CID","arg1_id":"15500","arg2_id":"15509","normalized":[]},{"id":"15523","type":"CID","arg1_id":"15500","arg2_id":"15510","normalized":[]},{"id":"15524","type":"CID","arg1_id":"15500","arg2_id":"15513","normalized":[]},{"id":"15525","type":"CID","arg1_id":"15504","arg2_id":"15499","normalized":[]},{"id":"15526","type":"CID","arg1_id":"15504","arg2_id":"15502","normalized":[]},{"id":"15527","type":"CID","arg1_id":"15504","arg2_id":"15503","normalized":[]},{"id":"15528","type":"CID","arg1_id":"15504","arg2_id":"15506","normalized":[]},{"id":"15529","type":"CID","arg1_id":"15504","arg2_id":"15507","normalized":[]},{"id":"15530","type":"CID","arg1_id":"15504","arg2_id":"15508","normalized":[]},{"id":"15531","type":"CID","arg1_id":"15504","arg2_id":"15509","normalized":[]},{"id":"15532","type":"CID","arg1_id":"15504","arg2_id":"15510","normalized":[]},{"id":"15533","type":"CID","arg1_id":"15504","arg2_id":"15513","normalized":[]},{"id":"15534","type":"CID","arg1_id":"15514","arg2_id":"15499","normalized":[]},{"id":"15535","type":"CID","arg1_id":"15514","arg2_id":"15502","normalized":[]},{"id":"15536","type":"CID","arg1_id":"15514","arg2_id":"15503","normalized":[]},{"id":"15537","type":"CID","arg1_id":"15514","arg2_id":"15506","normalized":[]},{"id":"15538","type":"CID","arg1_id":"15514","arg2_id":"15507","normalized":[]},{"id":"15539","type":"CID","arg1_id":"15514","arg2_id":"15508","normalized":[]},{"id":"15540","type":"CID","arg1_id":"15514","arg2_id":"15509","normalized":[]},{"id":"15541","type":"CID","arg1_id":"15514","arg2_id":"15510","normalized":[]},{"id":"15542","type":"CID","arg1_id":"15514","arg2_id":"15513","normalized":[]},{"id":"15543","type":"CID","arg1_id":"15501","arg2_id":"15499","normalized":[]},{"id":"15544","type":"CID","arg1_id":"15501","arg2_id":"15502","normalized":[]},{"id":"15545","type":"CID","arg1_id":"15501","arg2_id":"15503","normalized":[]},{"id":"15546","type":"CID","arg1_id":"15501","arg2_id":"15506","normalized":[]},{"id":"15547","type":"CID","arg1_id":"15501","arg2_id":"15507","normalized":[]},{"id":"15548","type":"CID","arg1_id":"15501","arg2_id":"15508","normalized":[]},{"id":"15549","type":"CID","arg1_id":"15501","arg2_id":"15509","normalized":[]}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{"id":"15570","document_id":"7880714","passages":[{"id":"15571","type":"title","text":["Auditory disturbance associated with interscalene brachial plexus block."],"offsets":[[0,72]]},{"id":"15572","type":"abstract","text":["We performed an audiometric study in 20 patients who underwent surgery of the shoulder region under an interscalene brachial plexus block (IBPB). Bupivacaine 0.75% with adrenaline was given followed by a 24-hr continuous infusion of 0.25% bupivacaine. Three audiometric threshold measurements (0.25-18 kHz) were made: the first before IBPB, the second 2-6 h after surgery and the third on the first day after operation. In four patients hearing impairment on the side of the block was demonstrated after operation, in three measurements on the day of surgery and in one on the following day. The frequencies at which the impairment occurred varied between patients; in one only low frequencies (0.25-0.5 kHz) were involved. The maximum change in threshold was 35 dB at 6 kHz measured at the end of the continuous infusion of bupivacaine. This patient had hearing threshold changes (15-20 dB) at 6-10 kHz on the opposite side also. IBPB may cause transient auditory dysfunction in the ipsilateral ear, possibly via an effect on sympathetic innervation."],"offsets":[[73,1124]]}],"entities":[{"id":"15573","type":"Chemical","text":["Bupivacaine"],"offsets":[[219,230]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"15574","type":"Chemical","text":["adrenaline"],"offsets":[[242,252]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"15575","type":"Chemical","text":["bupivacaine"],"offsets":[[312,323]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"15576","type":"Disease","text":["hearing impairment"],"offsets":[[510,528]],"normalized":[{"db_name":"MESH","db_id":"D034381"}]},{"id":"15577","type":"Chemical","text":["bupivacaine"],"offsets":[[898,909]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"15578","type":"Disease","text":["auditory dysfunction"],"offsets":[[1029,1049]],"normalized":[{"db_name":"MESH","db_id":"D006311"}]}],"events":[],"coreferences":[],"relations":[{"id":"15579","type":"CID","arg1_id":"15573","arg2_id":"15576","normalized":[]},{"id":"15580","type":"CID","arg1_id":"15575","arg2_id":"15576","normalized":[]},{"id":"15581","type":"CID","arg1_id":"15577","arg2_id":"15576","normalized":[]},{"id":"15582","type":"CID","arg1_id":"15574","arg2_id":"15576","normalized":[]}]}
{"id":"15583","document_id":"7102237","passages":[{"id":"15584","type":"title","text":["Midazolam compared with thiopentone as an induction agent."],"offsets":[[0,58]]},{"id":"15585","type":"abstract","text":["In patients premedicated with scopolamine + morphine (+5 mg nitrazepam the evening before surgery), the sleep-inducing effect of midazolam 0.15 mg\/kg i.v. was clearly slower in onset than that of thiopentone 4.67 mg\/kg i.v. Somewhat fewer cardiovascular and local sequelae were found in the midazolam group, but, although apnoea occurred less often in the midazolam group it lasted longer. On the whole, the differences between midazolam and thiopentone had no apparent clinical consequences. Midazolam is a new alternative agent for induction in combination anaesthesia."],"offsets":[[59,630]]}],"entities":[{"id":"15586","type":"Chemical","text":["Midazolam"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"15587","type":"Chemical","text":["thiopentone"],"offsets":[[24,35]],"normalized":[{"db_name":"MESH","db_id":"D013874"}]},{"id":"15588","type":"Chemical","text":["scopolamine"],"offsets":[[89,100]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"15589","type":"Chemical","text":["morphine"],"offsets":[[103,111]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"15590","type":"Chemical","text":["nitrazepam"],"offsets":[[119,129]],"normalized":[{"db_name":"MESH","db_id":"D009567"}]},{"id":"15591","type":"Chemical","text":["midazolam"],"offsets":[[188,197]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"15592","type":"Chemical","text":["thiopentone"],"offsets":[[255,266]],"normalized":[{"db_name":"MESH","db_id":"D013874"}]},{"id":"15593","type":"Chemical","text":["midazolam"],"offsets":[[350,359]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"15594","type":"Disease","text":["apnoea"],"offsets":[[381,387]],"normalized":[{"db_name":"MESH","db_id":"D001049"}]},{"id":"15595","type":"Chemical","text":["midazolam"],"offsets":[[415,424]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"15596","type":"Chemical","text":["midazolam"],"offsets":[[487,496]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]},{"id":"15597","type":"Chemical","text":["thiopentone"],"offsets":[[501,512]],"normalized":[{"db_name":"MESH","db_id":"D013874"}]},{"id":"15598","type":"Chemical","text":["Midazolam"],"offsets":[[552,561]],"normalized":[{"db_name":"MESH","db_id":"D008874"}]}],"events":[],"coreferences":[],"relations":[{"id":"15599","type":"CID","arg1_id":"15586","arg2_id":"15594","normalized":[]},{"id":"15600","type":"CID","arg1_id":"15591","arg2_id":"15594","normalized":[]},{"id":"15601","type":"CID","arg1_id":"15593","arg2_id":"15594","normalized":[]},{"id":"15602","type":"CID","arg1_id":"15595","arg2_id":"15594","normalized":[]},{"id":"15603","type":"CID","arg1_id":"15596","arg2_id":"15594","normalized":[]},{"id":"15604","type":"CID","arg1_id":"15598","arg2_id":"15594","normalized":[]},{"id":"15605","type":"CID","arg1_id":"15587","arg2_id":"15594","normalized":[]},{"id":"15606","type":"CID","arg1_id":"15592","arg2_id":"15594","normalized":[]},{"id":"15607","type":"CID","arg1_id":"15597","arg2_id":"15594","normalized":[]}]}
{"id":"15608","document_id":"6769133","passages":[{"id":"15609","type":"title","text":["Cardiotoxic and possible leukemogenic effects of adriamycin in nonhuman primates."],"offsets":[[0,81]]},{"id":"15610","type":"abstract","text":["10 monkeys (macaques) received adriamycin by monthly intravenous injections at 12 mg\/m2 (1 mg\/kg). 8 of the 10 monkeys developed congestive heart failure at an average cumulative adriamycin dose (310 mg\/m2) well below that considered the safe upper limit (550 mg\/m2) in man. Histologically, the myocardial lesions resembled those found in human anthracycline-induced cardiomyopathy. 1 of the 10 monkeys developed acute myeloblastic leukemia after receiving 324 mg\/m2 of adriamycin; the 10th monkey is alive and well 26 months after the last dose of drug. Our results suggest that adriamycin is a more potent cardiotoxin in monkeys than in man, and that leukemia may be a consequence of prolonged treatment with this drug."],"offsets":[[82,803]]}],"entities":[{"id":"15611","type":"Disease","text":["Cardiotoxic"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"15612","type":"Chemical","text":["adriamycin"],"offsets":[[49,59]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"15613","type":"Chemical","text":["adriamycin"],"offsets":[[113,123]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"15614","type":"Disease","text":["congestive heart failure"],"offsets":[[211,235]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"15615","type":"Chemical","text":["adriamycin"],"offsets":[[261,271]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"15616","type":"Disease","text":["myocardial lesions"],"offsets":[[377,395]],"normalized":[{"db_name":"MESH","db_id":"D001768"}]},{"id":"15617","type":"Chemical","text":["anthracycline"],"offsets":[[427,440]],"normalized":[{"db_name":"MESH","db_id":"D018943"}]},{"id":"15618","type":"Disease","text":["cardiomyopathy"],"offsets":[[449,463]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"15619","type":"Disease","text":["acute myeloblastic leukemia"],"offsets":[[495,522]],"normalized":[{"db_name":"MESH","db_id":"D015470"}]},{"id":"15620","type":"Chemical","text":["adriamycin"],"offsets":[[552,562]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"15621","type":"Chemical","text":["adriamycin"],"offsets":[[662,672]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"15622","type":"Disease","text":["leukemia"],"offsets":[[735,743]],"normalized":[{"db_name":"MESH","db_id":"D007938"}]}],"events":[],"coreferences":[],"relations":[{"id":"15623","type":"CID","arg1_id":"15612","arg2_id":"15614","normalized":[]},{"id":"15624","type":"CID","arg1_id":"15613","arg2_id":"15614","normalized":[]},{"id":"15625","type":"CID","arg1_id":"15615","arg2_id":"15614","normalized":[]},{"id":"15626","type":"CID","arg1_id":"15620","arg2_id":"15614","normalized":[]},{"id":"15627","type":"CID","arg1_id":"15621","arg2_id":"15614","normalized":[]},{"id":"15628","type":"CID","arg1_id":"15612","arg2_id":"15619","normalized":[]},{"id":"15629","type":"CID","arg1_id":"15613","arg2_id":"15619","normalized":[]},{"id":"15630","type":"CID","arg1_id":"15615","arg2_id":"15619","normalized":[]},{"id":"15631","type":"CID","arg1_id":"15620","arg2_id":"15619","normalized":[]},{"id":"15632","type":"CID","arg1_id":"15621","arg2_id":"15619","normalized":[]}]}
{"id":"15633","document_id":"6292680","passages":[{"id":"15634","type":"title","text":["Doxorubicin cardiomyopathy in children with left-sided Wilms tumor."],"offsets":[[0,67]]},{"id":"15635","type":"abstract","text":["Two children with Wilms tumor of the left kidney experienced severe anthracycline cardiomyopathy after irradiation to the tumor bed and conventional dosage of doxorubicin. The cardiomyopathy is attributed 1) to the fact that radiation fields for left Wilms tumor include the lower portion of the heart and 2) to the interaction of doxorubicin and irradiation on cardiac muscle. It is recommended that doxorubicin dosage be sharply restricted in children with Wilms tumor of the left kidney who receive postoperative irradiation."],"offsets":[[68,596]]}],"entities":[{"id":"15636","type":"Chemical","text":["Doxorubicin"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"15637","type":"Disease","text":["cardiomyopathy"],"offsets":[[12,26]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"15638","type":"Disease","text":["Wilms tumor"],"offsets":[[55,66]],"normalized":[{"db_name":"MESH","db_id":"D009396"}]},{"id":"15639","type":"Disease","text":["Wilms tumor"],"offsets":[[86,97]],"normalized":[{"db_name":"MESH","db_id":"D009396"}]},{"id":"15640","type":"Chemical","text":["anthracycline"],"offsets":[[136,149]],"normalized":[{"db_name":"MESH","db_id":"D018943"}]},{"id":"15641","type":"Disease","text":["cardiomyopathy"],"offsets":[[150,164]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"15642","type":"Disease","text":["tumor"],"offsets":[[190,195]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"15643","type":"Chemical","text":["doxorubicin"],"offsets":[[227,238]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"15644","type":"Disease","text":["cardiomyopathy"],"offsets":[[244,258]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"15645","type":"Disease","text":["Wilms tumor"],"offsets":[[319,330]],"normalized":[{"db_name":"MESH","db_id":"D009396"}]},{"id":"15646","type":"Chemical","text":["doxorubicin"],"offsets":[[399,410]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"15647","type":"Chemical","text":["doxorubicin"],"offsets":[[469,480]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"15648","type":"Disease","text":["Wilms tumor"],"offsets":[[527,538]],"normalized":[{"db_name":"MESH","db_id":"D009396"}]}],"events":[],"coreferences":[],"relations":[{"id":"15649","type":"CID","arg1_id":"15636","arg2_id":"15637","normalized":[]},{"id":"15650","type":"CID","arg1_id":"15636","arg2_id":"15641","normalized":[]},{"id":"15651","type":"CID","arg1_id":"15636","arg2_id":"15644","normalized":[]},{"id":"15652","type":"CID","arg1_id":"15643","arg2_id":"15637","normalized":[]},{"id":"15653","type":"CID","arg1_id":"15643","arg2_id":"15641","normalized":[]},{"id":"15654","type":"CID","arg1_id":"15643","arg2_id":"15644","normalized":[]},{"id":"15655","type":"CID","arg1_id":"15646","arg2_id":"15637","normalized":[]},{"id":"15656","type":"CID","arg1_id":"15646","arg2_id":"15641","normalized":[]},{"id":"15657","type":"CID","arg1_id":"15646","arg2_id":"15644","normalized":[]},{"id":"15658","type":"CID","arg1_id":"15647","arg2_id":"15637","normalized":[]},{"id":"15659","type":"CID","arg1_id":"15647","arg2_id":"15641","normalized":[]},{"id":"15660","type":"CID","arg1_id":"15647","arg2_id":"15644","normalized":[]}]}
{"id":"15661","document_id":"3969369","passages":[{"id":"15662","type":"title","text":["Promotional effects of testosterone and dietary fat on prostate carcinogenesis in genetically susceptible rats."],"offsets":[[0,111]]},{"id":"15663","type":"abstract","text":["Germfree (GF) Lobund strain Wistar (LW) rats, fed vegetable diet L-485, have developed prostate adenocarcinomas spontaneously (10% incidence) at average age 34 months. Conventional LW rats, implanted with testosterone at age 4 months, developed a higher incidence of prostate cancer after an average interval of 14 months: 24% had developed gross tumors, and 40% when it included microscopic tumors. Preliminary results indicate that testosterone-treated LW rats that were fed the same diet, which was supplemented with corn oil up to 20% fat, developed prostate cancer after intervals of 6-12 months. Aged GF Sprague-Dawley (SD) rats have not developed prostate cancer spontaneously. Conventional SD rats fed diet L-485 and treated with testosterone developed only prostatitis. Experimental designs should consider genetic susceptibility as a basic prerequisite for studies on experimental prostate cancer."],"offsets":[[112,1019]]}],"entities":[{"id":"15664","type":"Chemical","text":["testosterone"],"offsets":[[23,35]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"15665","type":"Disease","text":["carcinogenesis"],"offsets":[[64,78]],"normalized":[{"db_name":"MESH","db_id":"D063646"}]},{"id":"15666","type":"Disease","text":["prostate adenocarcinomas"],"offsets":[[199,223]],"normalized":[{"db_name":"MESH","db_id":"D011471"}]},{"id":"15667","type":"Chemical","text":["testosterone"],"offsets":[[317,329]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"15668","type":"Disease","text":["prostate cancer"],"offsets":[[379,394]],"normalized":[{"db_name":"MESH","db_id":"D011471"}]},{"id":"15669","type":"Disease","text":["tumors"],"offsets":[[459,465]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"15670","type":"Disease","text":["tumors"],"offsets":[[504,510]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"15671","type":"Chemical","text":["testosterone"],"offsets":[[546,558]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"15672","type":"Disease","text":["prostate cancer"],"offsets":[[666,681]],"normalized":[{"db_name":"MESH","db_id":"D011471"}]},{"id":"15673","type":"Disease","text":["prostate cancer"],"offsets":[[766,781]],"normalized":[{"db_name":"MESH","db_id":"D011471"}]},{"id":"15674","type":"Chemical","text":["testosterone"],"offsets":[[850,862]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"15675","type":"Disease","text":["prostatitis"],"offsets":[[878,889]],"normalized":[{"db_name":"MESH","db_id":"D011472"}]},{"id":"15676","type":"Disease","text":["prostate cancer"],"offsets":[[1003,1018]],"normalized":[{"db_name":"MESH","db_id":"D011471"}]}],"events":[],"coreferences":[],"relations":[{"id":"15677","type":"CID","arg1_id":"15664","arg2_id":"15666","normalized":[]},{"id":"15678","type":"CID","arg1_id":"15664","arg2_id":"15668","normalized":[]},{"id":"15679","type":"CID","arg1_id":"15664","arg2_id":"15672","normalized":[]},{"id":"15680","type":"CID","arg1_id":"15664","arg2_id":"15673","normalized":[]},{"id":"15681","type":"CID","arg1_id":"15664","arg2_id":"15676","normalized":[]},{"id":"15682","type":"CID","arg1_id":"15667","arg2_id":"15666","normalized":[]},{"id":"15683","type":"CID","arg1_id":"15667","arg2_id":"15668","normalized":[]},{"id":"15684","type":"CID","arg1_id":"15667","arg2_id":"15672","normalized":[]},{"id":"15685","type":"CID","arg1_id":"15667","arg2_id":"15673","normalized":[]},{"id":"15686","type":"CID","arg1_id":"15667","arg2_id":"15676","normalized":[]},{"id":"15687","type":"CID","arg1_id":"15671","arg2_id":"15666","normalized":[]},{"id":"15688","type":"CID","arg1_id":"15671","arg2_id":"15668","normalized":[]},{"id":"15689","type":"CID","arg1_id":"15671","arg2_id":"15672","normalized":[]},{"id":"15690","type":"CID","arg1_id":"15671","arg2_id":"15673","normalized":[]},{"id":"15691","type":"CID","arg1_id":"15671","arg2_id":"15676","normalized":[]},{"id":"15692","type":"CID","arg1_id":"15674","arg2_id":"15666","normalized":[]},{"id":"15693","type":"CID","arg1_id":"15674","arg2_id":"15668","normalized":[]},{"id":"15694","type":"CID","arg1_id":"15674","arg2_id":"15672","normalized":[]},{"id":"15695","type":"CID","arg1_id":"15674","arg2_id":"15673","normalized":[]},{"id":"15696","type":"CID","arg1_id":"15674","arg2_id":"15676","normalized":[]},{"id":"15697","type":"CID","arg1_id":"15664","arg2_id":"15675","normalized":[]},{"id":"15698","type":"CID","arg1_id":"15667","arg2_id":"15675","normalized":[]},{"id":"15699","type":"CID","arg1_id":"15671","arg2_id":"15675","normalized":[]},{"id":"15700","type":"CID","arg1_id":"15674","arg2_id":"15675","normalized":[]}]}
{"id":"15701","document_id":"3108839","passages":[{"id":"15702","type":"title","text":["Mitomycin C associated hemolytic uremic syndrome."],"offsets":[[0,49]]},{"id":"15703","type":"abstract","text":["Mitomycin C associated Hemolytic Uremic Syndrome (HUS) is a potentially fatal but uncommon condition that is not yet widely recognised. It consists of microangiopathic hemolytic anemia, thrombocytopenia and progressive renal failure associated with mitomycin C treatment and affects about 10% of patients treated with this agent. The renal failure usually develops about 8-10 mth after start of mitomycin C treatment and the mortality is approximately 60% from renal failure or pulmonary edema. Renal lesions are similar to those seen in idiopathic HUS and include arteriolar fibrin thrombi, expanded subendothelial zones in glomerular capillary walls, ischemic wrinkling of glomerular basement membranes and mesangiolysis. The mechanism of action is postulated as mitomycin C-induced endothelial cell damage. We describe the clinical course and pathological findings in a 65 yr-old man with gastric adenocarcinoma who developed renal failure and thrombocytopenia while on treatment with mitomycin C and died in pulmonary edema."],"offsets":[[50,1078]]}],"entities":[{"id":"15704","type":"Chemical","text":["Mitomycin C"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D016685"}]},{"id":"15705","type":"Disease","text":["hemolytic uremic syndrome"],"offsets":[[23,48]],"normalized":[{"db_name":"MESH","db_id":"D006463"}]},{"id":"15706","type":"Chemical","text":["Mitomycin C"],"offsets":[[50,61]],"normalized":[{"db_name":"MESH","db_id":"D016685"}]},{"id":"15707","type":"Disease","text":["Hemolytic Uremic Syndrome"],"offsets":[[73,98]],"normalized":[{"db_name":"MESH","db_id":"D006463"}]},{"id":"15708","type":"Disease","text":["HUS"],"offsets":[[100,103]],"normalized":[{"db_name":"MESH","db_id":"D006463"}]},{"id":"15709","type":"Disease","text":["hemolytic anemia"],"offsets":[[218,234]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"15710","type":"Disease","text":["thrombocytopenia"],"offsets":[[236,252]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"15711","type":"Disease","text":["renal failure"],"offsets":[[269,282]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"15712","type":"Chemical","text":["mitomycin C"],"offsets":[[299,310]],"normalized":[{"db_name":"MESH","db_id":"D016685"}]},{"id":"15713","type":"Disease","text":["renal failure"],"offsets":[[384,397]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"15714","type":"Chemical","text":["mitomycin C"],"offsets":[[445,456]],"normalized":[{"db_name":"MESH","db_id":"D016685"}]},{"id":"15715","type":"Disease","text":["renal failure"],"offsets":[[511,524]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"15716","type":"Disease","text":["pulmonary edema"],"offsets":[[528,543]],"normalized":[{"db_name":"MESH","db_id":"D011654"}]},{"id":"15717","type":"Disease","text":["Renal lesions"],"offsets":[[545,558]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"15718","type":"Disease","text":["HUS"],"offsets":[[599,602]],"normalized":[{"db_name":"MESH","db_id":"D006463"}]},{"id":"15719","type":"Disease","text":["thrombi"],"offsets":[[633,640]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]},{"id":"15720","type":"Disease","text":["ischemic"],"offsets":[[703,711]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"15721","type":"Chemical","text":["mitomycin C"],"offsets":[[815,826]],"normalized":[{"db_name":"MESH","db_id":"D016685"}]},{"id":"15722","type":"Disease","text":["gastric adenocarcinoma"],"offsets":[[942,964]],"normalized":[{"db_name":"MESH","db_id":"D013274"}]},{"id":"15723","type":"Disease","text":["renal failure"],"offsets":[[979,992]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"15724","type":"Disease","text":["thrombocytopenia"],"offsets":[[997,1013]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"15725","type":"Chemical","text":["mitomycin C"],"offsets":[[1038,1049]],"normalized":[{"db_name":"MESH","db_id":"D016685"}]},{"id":"15726","type":"Disease","text":["pulmonary 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{"id":"15781","document_id":"2466960","passages":[{"id":"15782","type":"title","text":["Continuous ambulatory ECG monitoring during fluorouracil therapy: a prospective study."],"offsets":[[0,86]]},{"id":"15783","type":"abstract","text":["Although there have been anecdotal reports of cardiac toxicity associated with fluorouracil (5-FU) therapy, this phenomenon has not been studied in a systematic fashion. We prospectively performed continuous ambulatory ECG monitoring on 25 patients undergoing 5-FU infusion for treatment of solid tumors in order to assess the incidence of ischemic ST changes. Patients were monitored for 23 +\/- 4 hours before 5-FU infusion, and 98 +\/- 9 hours during 5-FU infusion. Anginal episodes were rare: only one patient had angina (during 5-FU infusion). However, asymptomatic ST changes (greater than or equal to 1 mm ST deviation) were common: six of 25 patients (24%) had ST changes before 5-FU infusion v 17 (68%) during 5-FU infusion (P less than .002). The incidence of ischemic episodes per patient per hour was 0.05 +\/- 0.02 prior to 5-FU infusion v 0.13 +\/- 0.03 during 5-FU infusion (P less than .001); the duration of ECG changes was 0.6 +\/- 0.3 minutes per patient per hour before 5-FU v 1.9 +\/- 0.5 minutes per patient per hour during 5-FU (P less than .01). ECG changes were more common among patients with known coronary artery disease. There were two cases of sudden death, both of which occurred at the end of the chemotherapy course. We conclude that 5-FU infusion is associated with a significant increase in silent ST segment deviation suggestive of ischemia, particularly among patients with coronary artery disease. The mechanism and clinical significance of these ECG changes remain to be determined."],"offsets":[[87,1602]]}],"entities":[{"id":"15784","type":"Chemical","text":["fluorouracil"],"offsets":[[44,56]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"15785","type":"Disease","text":["cardiac 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{"id":"15878","document_id":"2320800","passages":[{"id":"15879","type":"title","text":["Lethal anuria complicating high dose ifosfamide chemotherapy in a breast cancer patient with an impaired renal function."],"offsets":[[0,120]]},{"id":"15880","type":"abstract","text":["A sixty-year-old woman with advanced breast cancer, previously treated with cisplatin, developed an irreversible lethal renal failure with anuria, the day after 5 g\/m2 bolus ifosfamide. Postrenal failure was excluded by echography. A prerenal component could have contributed to renal failure because of a transient hypotension, due to an increasing ascitis, occurring just before anuria. However, correction of the hemodynamic parameters did not improve renal function. Ifosfamide is a known nephrotoxic drug with demonstrated tubulopathies. We strongly suspect that this lethal anuria was mainly due to ifosfamide, occurring in a patient having received previous cisplatin chemotherapy and with poor kidney perfusion due to transient hypotension. We recommend careful use of ifosfamide in patients pretreated with nephrotoxic chemotherapy and inadequate renal perfusion."],"offsets":[[121,993]]}],"entities":[{"id":"15881","type":"Disease","text":["anuria"],"offsets":[[7,13]],"normalized":[{"db_name":"MESH","db_id":"D001002"}]},{"id":"15882","type":"Chemical","text":["ifosfamide"],"offsets":[[37,47]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"15883","type":"Disease","text":["breast cancer"],"offsets":[[66,79]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"15884","type":"Disease","text":["impaired renal function"],"offsets":[[96,119]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"15885","type":"Disease","text":["breast cancer"],"offsets":[[158,171]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"15886","type":"Chemical","text":["cisplatin"],"offsets":[[197,206]],"normalized":[{"db_name":"MESH","db_id":"D002945"}]},{"id":"15887","type":"Disease","text":["renal 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{"id":"15948","document_id":"2220369","passages":[{"id":"15949","type":"title","text":["Central vein thrombosis and topical dipivalyl epinephrine."],"offsets":[[0,58]]},{"id":"15950","type":"abstract","text":["A report is given on an 83-year-old female who acquired central vein thrombosis in her seeing eye one day after having started topical medication with dipivalyl epinephrine for advanced glaucoma discovered in the other eye. From present knowledge about the effects of adrenergic eye drops on ocular blood circulation, it is difficult to suggest an association between the two events, which may be coincidental only."],"offsets":[[59,474]]}],"entities":[{"id":"15951","type":"Disease","text":["vein thrombosis"],"offsets":[[8,23]],"normalized":[{"db_name":"MESH","db_id":"D020246"}]},{"id":"15952","type":"Chemical","text":["dipivalyl epinephrine"],"offsets":[[36,57]],"normalized":[{"db_name":"MESH","db_id":"C015173"}]},{"id":"15953","type":"Disease","text":["vein thrombosis"],"offsets":[[123,138]],"normalized":[{"db_name":"MESH","db_id":"D020246"}]},{"id":"15954","type":"Chemical","text":["dipivalyl epinephrine"],"offsets":[[210,231]],"normalized":[{"db_name":"MESH","db_id":"C015173"}]},{"id":"15955","type":"Disease","text":["glaucoma"],"offsets":[[245,253]],"normalized":[{"db_name":"MESH","db_id":"D005901"}]}],"events":[],"coreferences":[],"relations":[{"id":"15956","type":"CID","arg1_id":"15952","arg2_id":"15951","normalized":[]},{"id":"15957","type":"CID","arg1_id":"15952","arg2_id":"15953","normalized":[]},{"id":"15958","type":"CID","arg1_id":"15954","arg2_id":"15951","normalized":[]},{"id":"15959","type":"CID","arg1_id":"15954","arg2_id":"15953","normalized":[]}]}
{"id":"15960","document_id":"326460","passages":[{"id":"15961","type":"title","text":["Amelioration of bendrofluazide-induced hypokalemia by timolol."],"offsets":[[0,62]]},{"id":"15962","type":"abstract","text":["The beta adrenergic blocking drug, timolol, tended to correct the hypokalemia of short-term bendrofluazide treatment in 6 healthy male subjects and although the effect was small it was significant. Timolol also reduced the rise in plasma aldosterone and urine potassium excretion following bendrofluazide and increased the urine sodium\/potassium ratio. There was no evidence of a shift of potassium from the intracellular to the extracellular space."],"offsets":[[63,512]]}],"entities":[{"id":"15963","type":"Chemical","text":["bendrofluazide"],"offsets":[[16,30]],"normalized":[{"db_name":"MESH","db_id":"D001539"}]},{"id":"15964","type":"Disease","text":["hypokalemia"],"offsets":[[39,50]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"15965","type":"Chemical","text":["timolol"],"offsets":[[54,61]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"15966","type":"Chemical","text":["timolol"],"offsets":[[98,105]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"15967","type":"Disease","text":["hypokalemia"],"offsets":[[129,140]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"15968","type":"Chemical","text":["bendrofluazide"],"offsets":[[155,169]],"normalized":[{"db_name":"MESH","db_id":"D001539"}]},{"id":"15969","type":"Chemical","text":["Timolol"],"offsets":[[261,268]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"15970","type":"Chemical","text":["aldosterone"],"offsets":[[301,312]],"normalized":[{"db_name":"MESH","db_id":"D000450"}]},{"id":"15971","type":"Chemical","text":["potassium"],"offsets":[[323,332]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"15972","type":"Chemical","text":["bendrofluazide"],"offsets":[[353,367]],"normalized":[{"db_name":"MESH","db_id":"D001539"}]},{"id":"15973","type":"Chemical","text":["sodium"],"offsets":[[392,398]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"15974","type":"Chemical","text":["potassium"],"offsets":[[399,408]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"15975","type":"Chemical","text":["potassium"],"offsets":[[452,461]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]}],"events":[],"coreferences":[],"relations":[{"id":"15976","type":"CID","arg1_id":"15963","arg2_id":"15964","normalized":[]},{"id":"15977","type":"CID","arg1_id":"15963","arg2_id":"15967","normalized":[]},{"id":"15978","type":"CID","arg1_id":"15968","arg2_id":"15964","normalized":[]},{"id":"15979","type":"CID","arg1_id":"15968","arg2_id":"15967","normalized":[]},{"id":"15980","type":"CID","arg1_id":"15972","arg2_id":"15964","normalized":[]},{"id":"15981","type":"CID","arg1_id":"15972","arg2_id":"15967","normalized":[]}]}
{"id":"15982","document_id":"20331935","passages":[{"id":"15983","type":"title","text":["A cross-sectional evaluation of the effect of risperidone and selective serotonin reuptake inhibitors on bone mineral density in boys."],"offsets":[[0,134]]},{"id":"15984","type":"abstract","text":["OBJECTIVE: The aim of the present study was to investigate the effect of risperidone-induced hyperprolactinemia on trabecular bone mineral density (BMD) in children and adolescents. METHOD: Medically healthy 7- to 17-year-old males chronically treated, in a naturalistic setting, with risperidone were recruited for this cross-sectional study through child psychiatry outpatient clinics between November 2005 and June 2007. Anthropometric measurements and laboratory testing were conducted. The clinical diagnoses were based on chart review, and developmental and treatment history was obtained from the medical record. Volumetric BMD of the ultradistal radius was measured using peripheral quantitative computed tomography, and areal BMD of the lumbar spine was estimated using dual-energy x-ray absorptiometry. RESULTS: Hyperprolactinemia was present in 49% of 83 boys (n = 41) treated with risperidone for a mean of 2.9 years. Serum testosterone concentration increased with pubertal status but was not affected by hyperprolactinemia. As expected, bone mineral content and BMD increased with sexual maturity. After adjusting for the stage of sexual development and height and BMI z scores, serum prolactin was negatively associated with trabecular volumetric BMD at the ultradistal radius (P < .03). Controlling for relevant covariates, we also found treatment with selective serotonin reuptake inhibitors (SSRIs) to be associated with lower trabecular BMD at the radius (P = .03) and BMD z score at the lumbar spine (P < .05). These findings became more marked when the analysis was restricted to non-Hispanic white patients. Of 13 documented fractures, 3 occurred after risperidone and SSRIs were started, and none occurred in patients with hyperprolactinemia. CONCLUSIONS: This is the first study to link risperidone-induced hyperprolactinemia and SSRI treatment to lower BMD in children and adolescents. Future research should evaluate the longitudinal course of this adverse event to determine its temporal stability and whether a higher fracture rate ensues."],"offsets":[[135,2202]]}],"entities":[{"id":"15985","type":"Chemical","text":["risperidone"],"offsets":[[46,57]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"15986","type":"Chemical","text":["serotonin"],"offsets":[[72,81]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"15987","type":"Chemical","text":["risperidone"],"offsets":[[208,219]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"15988","type":"Disease","text":["hyperprolactinemia"],"offsets":[[228,246]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"15989","type":"Chemical","text":["risperidone"],"offsets":[[420,431]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"15990","type":"Disease","text":["Hyperprolactinemia"],"offsets":[[957,975]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"15991","type":"Chemical","text":["risperidone"],"offsets":[[1028,1039]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"15992","type":"Chemical","text":["testosterone"],"offsets":[[1071,1083]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"15993","type":"Disease","text":["hyperprolactinemia"],"offsets":[[1153,1171]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"15994","type":"Chemical","text":["serotonin"],"offsets":[[1514,1523]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"15995","type":"Disease","text":["fractures"],"offsets":[[1782,1791]],"normalized":[{"db_name":"MESH","db_id":"D050723"}]},{"id":"15996","type":"Chemical","text":["risperidone"],"offsets":[[1810,1821]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"15997","type":"Disease","text":["hyperprolactinemia"],"offsets":[[1881,1899]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"15998","type":"Chemical","text":["risperidone"],"offsets":[[1946,1957]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"15999","type":"Disease","text":["hyperprolactinemia"],"offsets":[[1966,1984]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]}],"events":[],"coreferences":[],"relations":[{"id":"16000","type":"CID","arg1_id":"15985","arg2_id":"15988","normalized":[]},{"id":"16001","type":"CID","arg1_id":"15985","arg2_id":"15990","normalized":[]},{"id":"16002","type":"CID","arg1_id":"15985","arg2_id":"15993","normalized":[]},{"id":"16003","type":"CID","arg1_id":"15985","arg2_id":"15997","normalized":[]},{"id":"16004","type":"CID","arg1_id":"15985","arg2_id":"15999","normalized":[]},{"id":"16005","type":"CID","arg1_id":"15987","arg2_id":"15988","normalized":[]},{"id":"16006","type":"CID","arg1_id":"15987","arg2_id":"15990","normalized":[]},{"id":"16007","type":"CID","arg1_id":"15987","arg2_id":"15993","normalized":[]},{"id":"16008","type":"CID","arg1_id":"15987","arg2_id":"15997","normalized":[]},{"id":"16009","type":"CID","arg1_id":"15987","arg2_id":"15999","normalized":[]},{"id":"16010","type":"CID","arg1_id":"15989","arg2_id":"15988","normalized":[]},{"id":"16011","type":"CID","arg1_id":"15989","arg2_id":"15990","normalized":[]},{"id":"16012","type":"CID","arg1_id":"15989","arg2_id":"15993","normalized":[]},{"id":"16013","type":"CID","arg1_id":"15989","arg2_id":"15997","normalized":[]},{"id":"16014","type":"CID","arg1_id":"15989","arg2_id":"15999","normalized":[]},{"id":"16015","type":"CID","arg1_id":"15991","arg2_id":"15988","normalized":[]},{"id":"16016","type":"CID","arg1_id":"15991","arg2_id":"15990","normalized":[]},{"id":"16017","type":"CID","arg1_id":"15991","arg2_id":"15993","normalized":[]},{"id":"16018","type":"CID","arg1_id":"15991","arg2_id":"15997","normalized":[]},{"id":"16019","type":"CID","arg1_id":"15991","arg2_id":"15999","normalized":[]},{"id":"16020","type":"CID","arg1_id":"15996","arg2_id":"15988","normalized":[]},{"id":"16021","type":"CID","arg1_id":"15996","arg2_id":"15990","normalized":[]},{"id":"16022","type":"CID","arg1_id":"15996","arg2_id":"15993","normalized":[]},{"id":"16023","type":"CID","arg1_id":"15996","arg2_id":"15997","normalized":[]},{"id":"16024","type":"CID","arg1_id":"15996","arg2_id":"15999","normalized":[]},{"id":"16025","type":"CID","arg1_id":"15998","arg2_id":"15988","normalized":[]},{"id":"16026","type":"CID","arg1_id":"15998","arg2_id":"15990","normalized":[]},{"id":"16027","type":"CID","arg1_id":"15998","arg2_id":"15993","normalized":[]},{"id":"16028","type":"CID","arg1_id":"15998","arg2_id":"15997","normalized":[]},{"id":"16029","type":"CID","arg1_id":"15998","arg2_id":"15999","normalized":[]}]}
{"id":"16030","document_id":"19707748","passages":[{"id":"16031","type":"title","text":["Seizures associated with levofloxacin: case presentation and literature review."],"offsets":[[0,79]]},{"id":"16032","type":"abstract","text":["PURPOSE: We present a case of a patient who developed seizures shortly after initiating treatment with levofloxacin and to discuss the potential drug-drug interactions related to the inhibition of cytochrome P450 (CYP) 1A2 in this case, as well as in other cases, of levofloxacin-induced seizures. METHODS: Several biomedical databases were searched including MEDLINE, Cochrane and Ovid. The main search terms utilized were case report and levofloxacin. The search was limited to studies published in English. RESULTS: Six cases of levofloxacin-induced seizures have been reported in the literature. Drug-drug interactions related to the inhibition of CYP1A2 by levofloxacin are likely involved in the clinical outcome of these cases. CONCLUSIONS: Clinicians are exhorted to pay close attention when initiating levofloxacin therapy in patients taking medications with epileptogenic properties that are CYP1A2 substrates."],"offsets":[[80,1000]]}],"entities":[{"id":"16033","type":"Disease","text":["Seizures"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"16034","type":"Chemical","text":["levofloxacin"],"offsets":[[25,37]],"normalized":[{"db_name":"MESH","db_id":"D064704"}]},{"id":"16035","type":"Disease","text":["seizures"],"offsets":[[134,142]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"16036","type":"Chemical","text":["levofloxacin"],"offsets":[[183,195]],"normalized":[{"db_name":"MESH","db_id":"D064704"}]},{"id":"16037","type":"Chemical","text":["levofloxacin"],"offsets":[[347,359]],"normalized":[{"db_name":"MESH","db_id":"D064704"}]},{"id":"16038","type":"Disease","text":["seizures"],"offsets":[[368,376]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"16039","type":"Chemical","text":["levofloxacin"],"offsets":[[520,532]],"normalized":[{"db_name":"MESH","db_id":"D064704"}]},{"id":"16040","type":"Chemical","text":["levofloxacin"],"offsets":[[612,624]],"normalized":[{"db_name":"MESH","db_id":"D064704"}]},{"id":"16041","type":"Disease","text":["seizures"],"offsets":[[633,641]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"16042","type":"Chemical","text":["levofloxacin"],"offsets":[[742,754]],"normalized":[{"db_name":"MESH","db_id":"D064704"}]},{"id":"16043","type":"Chemical","text":["levofloxacin"],"offsets":[[891,903]],"normalized":[{"db_name":"MESH","db_id":"D064704"}]}],"events":[],"coreferences":[],"relations":[{"id":"16044","type":"CID","arg1_id":"16034","arg2_id":"16033","normalized":[]},{"id":"16045","type":"CID","arg1_id":"16034","arg2_id":"16035","normalized":[]},{"id":"16046","type":"CID","arg1_id":"16034","arg2_id":"16038","normalized":[]},{"id":"16047","type":"CID","arg1_id":"16034","arg2_id":"16041","normalized":[]},{"id":"16048","type":"CID","arg1_id":"16036","arg2_id":"16033","normalized":[]},{"id":"16049","type":"CID","arg1_id":"16036","arg2_id":"16035","normalized":[]},{"id":"16050","type":"CID","arg1_id":"16036","arg2_id":"16038","normalized":[]},{"id":"16051","type":"CID","arg1_id":"16036","arg2_id":"16041","normalized":[]},{"id":"16052","type":"CID","arg1_id":"16037","arg2_id":"16033","normalized":[]},{"id":"16053","type":"CID","arg1_id":"16037","arg2_id":"16035","normalized":[]},{"id":"16054","type":"CID","arg1_id":"16037","arg2_id":"16038","normalized":[]},{"id":"16055","type":"CID","arg1_id":"16037","arg2_id":"16041","normalized":[]},{"id":"16056","type":"CID","arg1_id":"16039","arg2_id":"16033","normalized":[]},{"id":"16057","type":"CID","arg1_id":"16039","arg2_id":"16035","normalized":[]},{"id":"16058","type":"CID","arg1_id":"16039","arg2_id":"16038","normalized":[]},{"id":"16059","type":"CID","arg1_id":"16039","arg2_id":"16041","normalized":[]},{"id":"16060","type":"CID","arg1_id":"16040","arg2_id":"16033","normalized":[]},{"id":"16061","type":"CID","arg1_id":"16040","arg2_id":"16035","normalized":[]},{"id":"16062","type":"CID","arg1_id":"16040","arg2_id":"16038","normalized":[]},{"id":"16063","type":"CID","arg1_id":"16040","arg2_id":"16041","normalized":[]},{"id":"16064","type":"CID","arg1_id":"16042","arg2_id":"16033","normalized":[]},{"id":"16065","type":"CID","arg1_id":"16042","arg2_id":"16035","normalized":[]},{"id":"16066","type":"CID","arg1_id":"16042","arg2_id":"16038","normalized":[]},{"id":"16067","type":"CID","arg1_id":"16042","arg2_id":"16041","normalized":[]},{"id":"16068","type":"CID","arg1_id":"16043","arg2_id":"16033","normalized":[]},{"id":"16069","type":"CID","arg1_id":"16043","arg2_id":"16035","normalized":[]},{"id":"16070","type":"CID","arg1_id":"16043","arg2_id":"16038","normalized":[]},{"id":"16071","type":"CID","arg1_id":"16043","arg2_id":"16041","normalized":[]}]}
{"id":"16072","document_id":"19692487","passages":[{"id":"16073","type":"title","text":["Mice lacking mPGES-1 are resistant to lithium-induced polyuria."],"offsets":[[0,63]]},{"id":"16074","type":"abstract","text":["Cyclooxygenase-2 activity is required for the development of lithium-induced polyuria. However, the involvement of a specific, terminal prostaglandin (PG) isomerase has not been evaluated. The present study was undertaken to assess lithium-induced polyuria in mice deficient in microsomal prostaglandin E synthase-1 (mPGES-1). A 2-wk administration of LiCl (4 mmol.kg(-1).day(-1) ip) in mPGES-1 +\/+ mice led to a marked polyuria with hyposmotic urine. This was associated with elevated renal mPGES-1 protein expression and increased urine PGE(2) excretion. In contrast, mPGES-1 -\/- mice were largely resistant to lithium-induced polyuria and a urine concentrating defect, accompanied by nearly complete blockade of high urine PGE(2) and cAMP output. Immunoblotting, immunohistochemistry, and quantitative (q) RT-PCR consistently detected a significant decrease in aquaporin-2 (AQP2) protein expression in both the renal cortex and medulla of lithium-treated +\/+ mice. This decrease was significantly attenuated in the -\/- mice. qRT-PCR detected similar patterns of changes in AQP2 mRNA in the medulla but not in the cortex. Similarly, the total protein abundance of the Na-K-2Cl cotransporter (NKCC2) in the medulla but not in the cortex of the +\/+ mice was significantly reduced by lithium treatment. In contrast, the dowregulation of renal medullary NKCC2 expression was significantly attenuated in the -\/- mice. We conclude that mPGES-1-derived PGE(2) mediates lithium-induced polyuria likely via inhibition of AQP2 and NKCC2 expression."],"offsets":[[64,1604]]}],"entities":[{"id":"16075","type":"Chemical","text":["lithium"],"offsets":[[38,45]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"16076","type":"Disease","text":["polyuria"],"offsets":[[54,62]],"normalized":[{"db_name":"MESH","db_id":"D011141"}]},{"id":"16077","type":"Chemical","text":["lithium"],"offsets":[[125,132]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"16078","type":"Disease","text":["polyuria"],"offsets":[[141,149]],"normalized":[{"db_name":"MESH","db_id":"D011141"}]},{"id":"16079","type":"Chemical","text":["prostaglandin"],"offsets":[[200,213]],"normalized":[{"db_name":"MESH","db_id":"D011453"}]},{"id":"16080","type":"Chemical","text":["PG"],"offsets":[[215,217]],"normalized":[{"db_name":"MESH","db_id":"D011453"}]},{"id":"16081","type":"Chemical","text":["lithium"],"offsets":[[296,303]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"16082","type":"Disease","text":["polyuria"],"offsets":[[312,320]],"normalized":[{"db_name":"MESH","db_id":"D011141"}]},{"id":"16083","type":"Chemical","text":["prostaglandin E"],"offsets":[[353,368]],"normalized":[{"db_name":"MESH","db_id":"D011458"}]},{"id":"16084","type":"Chemical","text":["LiCl"],"offsets":[[416,420]],"normalized":[{"db_name":"MESH","db_id":"D018021"}]},{"id":"16085","type":"Disease","text":["polyuria"],"offsets":[[484,492]],"normalized":[{"db_name":"MESH","db_id":"D011141"}]},{"id":"16086","type":"Chemical","text":["PGE(2)"],"offsets":[[603,609]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"16087","type":"Chemical","text":["lithium"],"offsets":[[677,684]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"16088","type":"Disease","text":["polyuria"],"offsets":[[693,701]],"normalized":[{"db_name":"MESH","db_id":"D011141"}]},{"id":"16089","type":"Chemical","text":["PGE(2)"],"offsets":[[790,796]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"16090","type":"Chemical","text":["lithium"],"offsets":[[1006,1013]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"16091","type":"Chemical","text":["Na"],"offsets":[[1234,1236]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"16092","type":"Chemical","text":["K"],"offsets":[[1237,1238]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"16093","type":"Chemical","text":["Cl"],"offsets":[[1240,1242]],"normalized":[{"db_name":"MESH","db_id":"D002713"}]},{"id":"16094","type":"Chemical","text":["lithium"],"offsets":[[1347,1354]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"16095","type":"Chemical","text":["PGE(2)"],"offsets":[[1512,1518]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"16096","type":"Chemical","text":["lithium"],"offsets":[[1528,1535]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"16097","type":"Disease","text":["polyuria"],"offsets":[[1544,1552]],"normalized":[{"db_name":"MESH","db_id":"D011141"}]}],"events":[],"coreferences":[],"relations":[{"id":"16098","type":"CID","arg1_id":"16084","arg2_id":"16076","normalized":[]},{"id":"16099","type":"CID","arg1_id":"16084","arg2_id":"16078","normalized":[]},{"id":"16100","type":"CID","arg1_id":"16084","arg2_id":"16082","normalized":[]},{"id":"16101","type":"CID","arg1_id":"16084","arg2_id":"16085","normalized":[]},{"id":"16102","type":"CID","arg1_id":"16084","arg2_id":"16088","normalized":[]},{"id":"16103","type":"CID","arg1_id":"16084","arg2_id":"16097","normalized":[]}]}
{"id":"16104","document_id":"19289093","passages":[{"id":"16105","type":"title","text":["Identification of a simple and sensitive microplate method for the detection of oversulfated chondroitin sulfate in heparin products."],"offsets":[[0,133]]},{"id":"16106","type":"abstract","text":["Heparin is a commonly implemented anticoagulant used to treat critically ill patients. Recently, a number of commercial lots of heparin products were found to be contaminated with an oversulfated chondroitin sulfate (OSCS) derivative that could elicit a hypotensive response in pigs following a single high-dose infusion. Using both contaminated heparin products and the synthetically produced derivative, we showed that the OSCS produces dose-dependent hypotension in pigs. The no observed effect level (NOEL) for this contaminant appears to be approximately 1mg\/kg, corresponding to a contamination level of approximately 3%. We also demonstrated that OSCS can be identified in heparin products using a simple, inexpensive, commercially available heparin enzyme immunoassay (EIA) kit that has a limit of detection of approximately 0.1%, well below the NOEL. This kit may provide a useful method to test heparin products for contamination with oversulfated GAG derivatives."],"offsets":[[134,1108]]}],"entities":[{"id":"16107","type":"Chemical","text":["chondroitin sulfate"],"offsets":[[93,112]],"normalized":[{"db_name":"MESH","db_id":"D002809"}]},{"id":"16108","type":"Chemical","text":["heparin"],"offsets":[[116,123]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"16109","type":"Chemical","text":["Heparin"],"offsets":[[134,141]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"16110","type":"Chemical","text":["heparin"],"offsets":[[262,269]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"16111","type":"Chemical","text":["chondroitin sulfate"],"offsets":[[330,349]],"normalized":[{"db_name":"MESH","db_id":"D002809"}]},{"id":"16112","type":"Disease","text":["hypotensive"],"offsets":[[388,399]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"16113","type":"Chemical","text":["heparin"],"offsets":[[480,487]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"16114","type":"Disease","text":["hypotension"],"offsets":[[588,599]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"16115","type":"Chemical","text":["heparin"],"offsets":[[814,821]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"16116","type":"Chemical","text":["heparin"],"offsets":[[883,890]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"16117","type":"Chemical","text":["heparin"],"offsets":[[1039,1046]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]}],"events":[],"coreferences":[],"relations":[{"id":"16118","type":"CID","arg1_id":"16107","arg2_id":"16112","normalized":[]},{"id":"16119","type":"CID","arg1_id":"16107","arg2_id":"16114","normalized":[]},{"id":"16120","type":"CID","arg1_id":"16111","arg2_id":"16112","normalized":[]},{"id":"16121","type":"CID","arg1_id":"16111","arg2_id":"16114","normalized":[]}]}
{"id":"16122","document_id":"18627295","passages":[{"id":"16123","type":"title","text":["Doxorubicin cardiomyopathy-induced inflammation and apoptosis are attenuated by gene deletion of the kinin B1 receptor."],"offsets":[[0,119]]},{"id":"16124","type":"abstract","text":["Clinical use of the anthracycline doxorubicin (DOX) is limited by its cardiotoxic effects, which are attributed to the induction of apoptosis. To elucidate the possible role of the kinin B1 receptor (B1R) during the development of DOX cardiomyopathy, we studied B1R knockout mice (B1R(-\/-)) by investigating cardiac inflammation and apoptosis after induction of DOX-induced cardiomyopathy. DOX control mice showed cardiac dysfunction measured by pressure-volume loops in vivo. This was associated with a reduced activation state of AKT, as well as an increased bax\/bcl2 ratio in Western blots, indicating cardiac apoptosis. Furthermore, mRNA levels of the proinflammatory cytokine interleukin 6 were increased in the cardiac tissue. In DOX B1R(-\/-) mice, cardiac dysfunction was improved compared to DOX control mice, which was associated with normalization of the bax\/bcl-2 ratio and interleukin 6, as well as AKT activation state. These findings suggest that B1R is detrimental in DOX cardiomyopathy in that it mediates the inflammatory response and apoptosis. These insights might have useful implications for future studies utilizing B1R antagonists for treatment of human DOX cardiomyopathy."],"offsets":[[120,1316]]}],"entities":[{"id":"16125","type":"Chemical","text":["Doxorubicin"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"16126","type":"Disease","text":["cardiomyopathy"],"offsets":[[12,26]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"16127","type":"Disease","text":["inflammation"],"offsets":[[35,47]],"normalized":[{"db_name":"MESH","db_id":"D007249"}]},{"id":"16128","type":"Chemical","text":["anthracycline"],"offsets":[[140,153]],"normalized":[{"db_name":"MESH","db_id":"D018943"}]},{"id":"16129","type":"Chemical","text":["doxorubicin"],"offsets":[[154,165]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"16130","type":"Chemical","text":["DOX"],"offsets":[[167,170]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"16131","type":"Disease","text":["cardiotoxic"],"offsets":[[190,201]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"16132","type":"Chemical","text":["DOX"],"offsets":[[351,354]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"16133","type":"Disease","text":["cardiomyopathy"],"offsets":[[355,369]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"16134","type":"Disease","text":["inflammation"],"offsets":[[436,448]],"normalized":[{"db_name":"MESH","db_id":"D007249"}]},{"id":"16135","type":"Chemical","text":["DOX"],"offsets":[[482,485]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"16136","type":"Disease","text":["cardiomyopathy"],"offsets":[[494,508]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"16137","type":"Chemical","text":["DOX"],"offsets":[[510,513]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"16138","type":"Disease","text":["cardiac dysfunction"],"offsets":[[534,553]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"16139","type":"Disease","text":["cardiac apoptosis"],"offsets":[[725,742]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"16140","type":"Chemical","text":["DOX"],"offsets":[[856,859]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"16141","type":"Disease","text":["cardiac dysfunction"],"offsets":[[875,894]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"16142","type":"Chemical","text":["DOX"],"offsets":[[920,923]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"16143","type":"Chemical","text":["DOX"],"offsets":[[1103,1106]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"16144","type":"Disease","text":["cardiomyopathy"],"offsets":[[1107,1121]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"16145","type":"Chemical","text":["DOX"],"offsets":[[1297,1300]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"16146","type":"Disease","text":["cardiomyopathy"],"offsets":[[1301,1315]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]}],"events":[],"coreferences":[],"relations":[{"id":"16147","type":"CID","arg1_id":"16125","arg2_id":"16126","normalized":[]},{"id":"16148","type":"CID","arg1_id":"16125","arg2_id":"16133","normalized":[]},{"id":"16149","type":"CID","arg1_id":"16125","arg2_id":"16136","normalized":[]},{"id":"16150","type":"CID","arg1_id":"16125","arg2_id":"16144","normalized":[]},{"id":"16151","type":"CID","arg1_id":"16125","arg2_id":"16146","normalized":[]},{"id":"16152","type":"CID","arg1_id":"16129","arg2_id":"16126","normalized":[]},{"id":"16153","type":"CID","arg1_id":"16129","arg2_id":"16133","normalized":[]},{"id":"16154","type":"CID","arg1_id":"16129","arg2_id":"16136","normalized":[]},{"id":"16155","type":"CID","arg1_id":"16129","arg2_id":"16144","normalized":[]},{"id":"16156","type":"CID","arg1_id":"16129","arg2_id":"16146","normalized":[]},{"id":"16157","type":"CID","arg1_id":"16130","arg2_id":"16126","normalized":[]},{"id":"16158","type":"CID","arg1_id":"16130","arg2_id":"16133","normalized":[]},{"id":"16159","type":"CID","arg1_id":"16130","arg2_id":"16136","normalized":[]},{"id":"16160","type":"CID","arg1_id":"16130","arg2_id":"16144","normalized":[]},{"id":"16161","type":"CID","arg1_id":"16130","arg2_id":"16146","normalized":[]},{"id":"16162","type":"CID","arg1_id":"16132","arg2_id":"16126","normalized":[]},{"id":"16163","type":"CID","arg1_id":"16132","arg2_id":"16133","normalized":[]},{"id":"16164","type":"CID","arg1_id":"16132","arg2_id":"16136","normalized":[]},{"id":"16165","type":"CID","arg1_id":"16132","arg2_id":"16144","normalized":[]},{"id":"16166","type":"CID","arg1_id":"16132","arg2_id":"16146","normalized":[]},{"id":"16167","type":"CID","arg1_id":"16135","arg2_id":"16126","normalized":[]},{"id":"16168","type":"CID","arg1_id":"16135","arg2_id":"16133","normalized":[]},{"id":"16169","type":"CID","arg1_id":"16135","arg2_id":"16136","normalized":[]},{"id":"16170","type":"CID","arg1_id":"16135","arg2_id":"16144","normalized":[]},{"id":"16171","type":"CID","arg1_id":"16135","arg2_id":"16146","normalized":[]},{"id":"16172","type":"CID","arg1_id":"16137","arg2_id":"16126","normalized":[]},{"id":"16173","type":"CID","arg1_id":"16137","arg2_id":"16133","normalized":[]},{"id":"16174","type":"CID","arg1_id":"16137","arg2_id":"16136","normalized":[]},{"id":"16175","type":"CID","arg1_id":"16137","arg2_id":"16144","normalized":[]},{"id":"16176","type":"CID","arg1_id":"16137","arg2_id":"16146","normalized":[]},{"id":"16177","type":"CID","arg1_id":"16140","arg2_id":"16126","normalized":[]},{"id":"16178","type":"CID","arg1_id":"16140","arg2_id":"16133","normalized":[]},{"id":"16179","type":"CID","arg1_id":"16140","arg2_id":"16136","normalized":[]},{"id":"16180","type":"CID","arg1_id":"16140","arg2_id":"16144","normalized":[]},{"id":"16181","type":"CID","arg1_id":"16140","arg2_id":"16146","normalized":[]},{"id":"16182","type":"CID","arg1_id":"16142","arg2_id":"16126","normalized":[]},{"id":"16183","type":"CID","arg1_id":"16142","arg2_id":"16133","normalized":[]},{"id":"16184","type":"CID","arg1_id":"16142","arg2_id":"16136","normalized":[]},{"id":"16185","type":"CID","arg1_id":"16142","arg2_id":"16144","normalized":[]},{"id":"16186","type":"CID","arg1_id":"16142","arg2_id":"16146","normalized":[]},{"id":"16187","type":"CID","arg1_id":"16143","arg2_id":"16126","normalized":[]},{"id":"16188","type":"CID","arg1_id":"16143","arg2_id":"16133","normalized":[]},{"id":"16189","type":"CID","arg1_id":"16143","arg2_id":"16136","normalized":[]},{"id":"16190","type":"CID","arg1_id":"16143","arg2_id":"16144","normalized":[]},{"id":"16191","type":"CID","arg1_id":"16143","arg2_id":"16146","normalized":[]},{"id":"16192","type":"CID","arg1_id":"16145","arg2_id":"16126","normalized":[]},{"id":"16193","type":"CID","arg1_id":"16145","arg2_id":"16133","normalized":[]},{"id":"16194","type":"CID","arg1_id":"16145","arg2_id":"16136","normalized":[]},{"id":"16195","type":"CID","arg1_id":"16145","arg2_id":"16144","normalized":[]},{"id":"16196","type":"CID","arg1_id":"16145","arg2_id":"16146","normalized":[]}]}
{"id":"16197","document_id":"18405372","passages":[{"id":"16198","type":"title","text":["Hepatotoxicity associated with sulfasalazine in inflammatory arthritis: A case series from a local surveillance of serious adverse events."],"offsets":[[0,138]]},{"id":"16199","type":"abstract","text":["BACKGROUND: Spontaneous reporting systems for adverse drug reactions (ADRs) are handicapped by under-reporting and limited detail on individual cases. We report an investigation from a local surveillance for serious adverse drug reactions associated with disease modifying anti-rheumatic drugs that was triggered by the occurrence of liver failure in two of our patients. METHODS: Serious ADR reports have been solicited from local clinicians by regular postcards over the past seven years. Patients', who had hepatotoxicity on sulfasalazine and met a definition of a serious ADR, were identified. Two clinicians reviewed structured case reports and assessed causality by consensus and by using a causality assessment instrument. The likely frequency of hepatotoxicity with sulfasalazine was estimated by making a series of conservative assumptions. RESULTS: Ten cases were identified: eight occurred during surveillance. Eight patients were hospitalised, two in hepatic failure - one died after a liver transplant. All but one event occurred within 6 weeks of treatment. Seven patients had a skin rash, three eosinophilia and one interstitial nephritis. Five patients were of Black British of African or Caribbean descent. Liver enzymes showed a hepatocellular pattern in four cases and a mixed pattern in six. Drug-related hepatotoxicity was judged probable or highly probable in 8 patients. The likely frequency of serious hepatotoxicity with sulfasalazine was estimated at 0.4% of treated patients. CONCLUSION: Serious hepatotoxicity associated with sulfasalazine appears to be under-appreciated and intensive monitoring and vigilance in the first 6 weeks of treatment is especially important."],"offsets":[[139,1836]]}],"entities":[{"id":"16200","type":"Disease","text":["Hepatotoxicity"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"16201","type":"Chemical","text":["sulfasalazine"],"offsets":[[31,44]],"normalized":[{"db_name":"MESH","db_id":"D012460"}]},{"id":"16202","type":"Disease","text":["arthritis"],"offsets":[[61,70]],"normalized":[{"db_name":"MESH","db_id":"D001168"}]},{"id":"16203","type":"Disease","text":["liver failure"],"offsets":[[473,486]],"normalized":[{"db_name":"MESH","db_id":"D017093"}]},{"id":"16204","type":"Disease","text":["hepatotoxicity"],"offsets":[[649,663]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"16205","type":"Chemical","text":["sulfasalazine"],"offsets":[[667,680]],"normalized":[{"db_name":"MESH","db_id":"D012460"}]},{"id":"16206","type":"Disease","text":["hepatotoxicity"],"offsets":[[893,907]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"16207","type":"Chemical","text":["sulfasalazine"],"offsets":[[913,926]],"normalized":[{"db_name":"MESH","db_id":"D012460"}]},{"id":"16208","type":"Disease","text":["hepatic failure"],"offsets":[[1102,1117]],"normalized":[{"db_name":"MESH","db_id":"D017093"}]},{"id":"16209","type":"Disease","text":["skin rash"],"offsets":[[1232,1241]],"normalized":[{"db_name":"MESH","db_id":"D005076"}]},{"id":"16210","type":"Disease","text":["eosinophilia"],"offsets":[[1249,1261]],"normalized":[{"db_name":"MESH","db_id":"D004802"}]},{"id":"16211","type":"Disease","text":["interstitial nephritis"],"offsets":[[1270,1292]],"normalized":[{"db_name":"MESH","db_id":"D009395"}]},{"id":"16212","type":"Disease","text":["hepatotoxicity"],"offsets":[[1464,1478]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"16213","type":"Disease","text":["hepatotoxicity"],"offsets":[[1565,1579]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"16214","type":"Chemical","text":["sulfasalazine"],"offsets":[[1585,1598]],"normalized":[{"db_name":"MESH","db_id":"D012460"}]},{"id":"16215","type":"Disease","text":["hepatotoxicity"],"offsets":[[1662,1676]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"16216","type":"Chemical","text":["sulfasalazine"],"offsets":[[1693,1706]],"normalized":[{"db_name":"MESH","db_id":"D012460"}]}],"events":[],"coreferences":[],"relations":[{"id":"16217","type":"CID","arg1_id":"16201","arg2_id":"16200","normalized":[]},{"id":"16218","type":"CID","arg1_id":"16201","arg2_id":"16204","normalized":[]},{"id":"16219","type":"CID","arg1_id":"16201","arg2_id":"16206","normalized":[]},{"id":"16220","type":"CID","arg1_id":"16201","arg2_id":"16212","normalized":[]},{"id":"16221","type":"CID","arg1_id":"16201","arg2_id":"16213","normalized":[]},{"id":"16222","type":"CID","arg1_id":"16201","arg2_id":"16215","normalized":[]},{"id":"16223","type":"CID","arg1_id":"16205","arg2_id":"16200","normalized":[]},{"id":"16224","type":"CID","arg1_id":"16205","arg2_id":"16204","normalized":[]},{"id":"16225","type":"CID","arg1_id":"16205","arg2_id":"16206","normalized":[]},{"id":"16226","type":"CID","arg1_id":"16205","arg2_id":"16212","normalized":[]},{"id":"16227","type":"CID","arg1_id":"16205","arg2_id":"16213","normalized":[]},{"id":"16228","type":"CID","arg1_id":"16205","arg2_id":"16215","normalized":[]},{"id":"16229","type":"CID","arg1_id":"16207","arg2_id":"16200","normalized":[]},{"id":"16230","type":"CID","arg1_id":"16207","arg2_id":"16204","normalized":[]},{"id":"16231","type":"CID","arg1_id":"16207","arg2_id":"16206","normalized":[]},{"id":"16232","type":"CID","arg1_id":"16207","arg2_id":"16212","normalized":[]},{"id":"16233","type":"CID","arg1_id":"16207","arg2_id":"16213","normalized":[]},{"id":"16234","type":"CID","arg1_id":"16207","arg2_id":"16215","normalized":[]},{"id":"16235","type":"CID","arg1_id":"16214","arg2_id":"16200","normalized":[]},{"id":"16236","type":"CID","arg1_id":"16214","arg2_id":"16204","normalized":[]},{"id":"16237","type":"CID","arg1_id":"16214","arg2_id":"16206","normalized":[]},{"id":"16238","type":"CID","arg1_id":"16214","arg2_id":"16212","normalized":[]},{"id":"16239","type":"CID","arg1_id":"16214","arg2_id":"16213","normalized":[]},{"id":"16240","type":"CID","arg1_id":"16214","arg2_id":"16215","normalized":[]},{"id":"16241","type":"CID","arg1_id":"16216","arg2_id":"16200","normalized":[]},{"id":"16242","type":"CID","arg1_id":"16216","arg2_id":"16204","normalized":[]},{"id":"16243","type":"CID","arg1_id":"16216","arg2_id":"16206","normalized":[]},{"id":"16244","type":"CID","arg1_id":"16216","arg2_id":"16212","normalized":[]},{"id":"16245","type":"CID","arg1_id":"16216","arg2_id":"16213","normalized":[]},{"id":"16246","type":"CID","arg1_id":"16216","arg2_id":"16215","normalized":[]}]}
{"id":"16247","document_id":"18356633","passages":[{"id":"16248","type":"title","text":["An evaluation of amikacin nephrotoxicity in the hematology\/oncology population."],"offsets":[[0,79]]},{"id":"16249","type":"abstract","text":["Amikacin is an aminoglycoside commonly used to provide empirical double gram-negative treatment for febrile neutropenia and other suspected infections. Strategies of extended-interval and conventional dosing have been utilized extensively in the general medical population; however, data are lacking to support a dosing strategy in the hematology\/oncology population. To evaluate amikacin-associated nephrotoxicity in an adult hematology\/oncology population, a prospective, randomized, open-label trial was conducted at a university-affiliated medical center. Forty patients with a diagnosis consistent with a hematologic\/oncologic disorder that required treatment with an aminoglycoside were randomized to either conventional or extended-interval amikacin. The occurrence of nephrotoxicity by means of an increase in serum creatinine and evaluation of efficacy via amikacin serum concentrations with respective pathogens were assessed. The occurrence of nephrotoxicity was similar between the conventional and extended-interval groups, at 10% and 5%, respectively (P = 1.00). Six patients in the conventional group had a positive culture, compared with none in the extended-interval group (P = 0.002). The occurrence of nephrotoxicity was similar between the two dosing regimens, but the distribution of risk factors was variable between the two groups. Efficacy could not be assessed."],"offsets":[[80,1466]]}],"entities":[{"id":"16250","type":"Chemical","text":["amikacin"],"offsets":[[17,25]],"normalized":[{"db_name":"MESH","db_id":"D000583"}]},{"id":"16251","type":"Disease","text":["nephrotoxicity"],"offsets":[[26,40]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"16252","type":"Chemical","text":["Amikacin"],"offsets":[[80,88]],"normalized":[{"db_name":"MESH","db_id":"D000583"}]},{"id":"16253","type":"Chemical","text":["aminoglycoside"],"offsets":[[95,109]],"normalized":[{"db_name":"MESH","db_id":"D000617"}]},{"id":"16254","type":"Disease","text":["febrile neutropenia"],"offsets":[[180,199]],"normalized":[{"db_name":"MESH","db_id":"D009503"}]},{"id":"16255","type":"Disease","text":["infections"],"offsets":[[220,230]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"16256","type":"Chemical","text":["amikacin"],"offsets":[[460,468]],"normalized":[{"db_name":"MESH","db_id":"D000583"}]},{"id":"16257","type":"Disease","text":["nephrotoxicity"],"offsets":[[480,494]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"16258","type":"Disease","text":["hematologic\/oncologic disorder"],"offsets":[[690,720]],"normalized":[{"db_name":"MESH","db_id":"D006402"},{"db_name":"MESH","db_id":"D009369"}]},{"id":"16259","type":"Disease","text":["hematologic","disorder"],"offsets":[[690,701],[712,720]],"normalized":[{"db_name":"MESH","db_id":"D006402"}]},{"id":"16260","type":"Disease","text":["oncologic disorder"],"offsets":[[702,720]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"16261","type":"Chemical","text":["aminoglycoside"],"offsets":[[753,767]],"normalized":[{"db_name":"MESH","db_id":"D000617"}]},{"id":"16262","type":"Chemical","text":["amikacin"],"offsets":[[828,836]],"normalized":[{"db_name":"MESH","db_id":"D000583"}]},{"id":"16263","type":"Disease","text":["nephrotoxicity"],"offsets":[[856,870]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"16264","type":"Chemical","text":["creatinine"],"offsets":[[904,914]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"16265","type":"Chemical","text":["amikacin"],"offsets":[[946,954]],"normalized":[{"db_name":"MESH","db_id":"D000583"}]},{"id":"16266","type":"Disease","text":["nephrotoxicity"],"offsets":[[1035,1049]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"16267","type":"Disease","text":["nephrotoxicity"],"offsets":[[1301,1315]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"16268","type":"CID","arg1_id":"16250","arg2_id":"16251","normalized":[]},{"id":"16269","type":"CID","arg1_id":"16250","arg2_id":"16257","normalized":[]},{"id":"16270","type":"CID","arg1_id":"16250","arg2_id":"16263","normalized":[]},{"id":"16271","type":"CID","arg1_id":"16250","arg2_id":"16266","normalized":[]},{"id":"16272","type":"CID","arg1_id":"16250","arg2_id":"16267","normalized":[]},{"id":"16273","type":"CID","arg1_id":"16252","arg2_id":"16251","normalized":[]},{"id":"16274","type":"CID","arg1_id":"16252","arg2_id":"16257","normalized":[]},{"id":"16275","type":"CID","arg1_id":"16252","arg2_id":"16263","normalized":[]},{"id":"16276","type":"CID","arg1_id":"16252","arg2_id":"16266","normalized":[]},{"id":"16277","type":"CID","arg1_id":"16252","arg2_id":"16267","normalized":[]},{"id":"16278","type":"CID","arg1_id":"16256","arg2_id":"16251","normalized":[]},{"id":"16279","type":"CID","arg1_id":"16256","arg2_id":"16257","normalized":[]},{"id":"16280","type":"CID","arg1_id":"16256","arg2_id":"16263","normalized":[]},{"id":"16281","type":"CID","arg1_id":"16256","arg2_id":"16266","normalized":[]},{"id":"16282","type":"CID","arg1_id":"16256","arg2_id":"16267","normalized":[]},{"id":"16283","type":"CID","arg1_id":"16262","arg2_id":"16251","normalized":[]},{"id":"16284","type":"CID","arg1_id":"16262","arg2_id":"16257","normalized":[]},{"id":"16285","type":"CID","arg1_id":"16262","arg2_id":"16263","normalized":[]},{"id":"16286","type":"CID","arg1_id":"16262","arg2_id":"16266","normalized":[]},{"id":"16287","type":"CID","arg1_id":"16262","arg2_id":"16267","normalized":[]},{"id":"16288","type":"CID","arg1_id":"16265","arg2_id":"16251","normalized":[]},{"id":"16289","type":"CID","arg1_id":"16265","arg2_id":"16257","normalized":[]},{"id":"16290","type":"CID","arg1_id":"16265","arg2_id":"16263","normalized":[]},{"id":"16291","type":"CID","arg1_id":"16265","arg2_id":"16266","normalized":[]},{"id":"16292","type":"CID","arg1_id":"16265","arg2_id":"16267","normalized":[]}]}
{"id":"16293","document_id":"16574713","passages":[{"id":"16294","type":"title","text":["Memory function and serotonin transporter promoter gene polymorphism in ecstasy (MDMA) users."],"offsets":[[0,93]]},{"id":"16295","type":"abstract","text":["Although 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) has been shown to damage brain serotonin (5-HT) neurons in animals and possibly humans, little is known about the long-term consequences of MDMA-induced 5-HT neurotoxic lesions on functions in which 5-HT is involved, such as cognitive function. Because 5-HT transporters play a key element in the regulation of synaptic 5-HT transmission it may be important to control for the potential covariance effect of a polymorphism in the 5-HT transporter promoter gene region (5-HTTLPR) when studying the effects of MDMA as well as cognitive functioning. The aim of the study was to investigate the effects of moderate and heavy MDMA use on cognitive function, as well as the effects of long-term abstention from MDMA, in subjects genotyped for 5-HTTLPR. A second aim of the study was to determine whether these effects differ for females and males. Fifteen moderate MDMA users (<55 lifetime tablets), 22 heavy MDMA+ users (>55 lifetime tablets), 16 ex-MDMA+ users (last tablet > 1 year ago) and 13 controls were compared on a battery of neuropsychological tests. DNA from peripheral nuclear blood cells was genotyped for 5-HTTLPR using standard polymerase chain reaction methods.A significant group effect was observed only on memory function tasks (p = 0.04) but not on reaction times (p = 0.61) or attention\/executive functioning (p = 0.59). Heavy and ex-MDMA+ users performed significantly poorer on memory tasks than controls. In contrast, no evidence of memory impairment was observed in moderate MDMA users. No significant effect of 5-HTTLPR or gender was observed. While the use of MDMA in quantities that may be considered \"moderate\" is not associated with impaired memory functioning, heavy use of MDMA use may lead to long lasting memory impairments. No effect of 5-HTTLPR or gender on memory function or MDMA use was observed."],"offsets":[[94,1985]]}],"entities":[{"id":"16296","type":"Chemical","text":["serotonin"],"offsets":[[20,29]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"16297","type":"Chemical","text":["ecstasy"],"offsets":[[72,79]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"16298","type":"Chemical","text":["MDMA"],"offsets":[[81,85]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"16299","type":"Chemical","text":["3,4-methylenedioxymethamphetamine"],"offsets":[[103,136]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"16300","type":"Chemical","text":["MDMA"],"offsets":[[138,142]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"16301","type":"Chemical","text":["ecstasy"],"offsets":[[146,153]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"16302","type":"Chemical","text":["serotonin"],"offsets":[[186,195]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"16303","type":"Chemical","text":["5-HT"],"offsets":[[197,201]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"16304","type":"Chemical","text":["MDMA"],"offsets":[[295,299]],"normalized":[{"db_name":"MESH","db_id":"D018817"}]},{"id":"16305","type":"Chemical","text":["5-HT"],"offsets":[[308,312]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"16306","type":"Disease","text":["neurotoxic 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{"id":"16376","document_id":"15638391","passages":[{"id":"16377","type":"title","text":["Aging process of epithelial cells of the rat prostate lateral lobe in experimental hyperprolactinemia induced by haloperidol."],"offsets":[[0,125]]},{"id":"16378","type":"abstract","text":["The aim of the study was to examine the influence of hyperprolactinemia, induced by haloperidol (HAL) on age related morphology and function changes of epithelial cells in rat prostate lateral lobe. The study was performed on sexually mature male rats. Serum concentrations of prolactin (PRL) and testosterone (T) were measured. Tissue sections were evaluated with light and electron microscopy. Immunohistochemical reactions for Anti-Proliferating Cell Nuclear Antigen (PCNA) were performed. In rats of the experimental group, the mean concentration of: PRL was more than twice higher, whereas T concentration was almost twice lower than that in the control group. Light microscopy visualized the following: hypertrophy and epithelium hyperplasia of the glandular ducts, associated with increased PCNA expression. Electron microscopy revealed changes in columnar epithelial cells, concerning organelles, engaged in protein synthesis and secretion."],"offsets":[[126,1074]]}],"entities":[{"id":"16379","type":"Disease","text":["hyperprolactinemia"],"offsets":[[83,101]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"16380","type":"Chemical","text":["haloperidol"],"offsets":[[113,124]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"16381","type":"Disease","text":["hyperprolactinemia"],"offsets":[[179,197]],"normalized":[{"db_name":"MESH","db_id":"D006966"}]},{"id":"16382","type":"Chemical","text":["haloperidol"],"offsets":[[210,221]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"16383","type":"Chemical","text":["HAL"],"offsets":[[223,226]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"16384","type":"Chemical","text":["PRL"],"offsets":[[414,417]],"normalized":[{"db_name":"MESH","db_id":"D011388"}]},{"id":"16385","type":"Chemical","text":["testosterone"],"offsets":[[423,435]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"16386","type":"Chemical","text":["T"],"offsets":[[437,438]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"16387","type":"Chemical","text":["PRL"],"offsets":[[681,684]],"normalized":[{"db_name":"MESH","db_id":"D011388"}]},{"id":"16388","type":"Chemical","text":["T"],"offsets":[[721,722]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"16389","type":"Disease","text":["hypertrophy"],"offsets":[[835,846]],"normalized":[{"db_name":"MESH","db_id":"D006984"}]},{"id":"16390","type":"Disease","text":["hyperplasia"],"offsets":[[862,873]],"normalized":[{"db_name":"MESH","db_id":"D006965"}]}],"events":[],"coreferences":[],"relations":[{"id":"16391","type":"CID","arg1_id":"16380","arg2_id":"16379","normalized":[]},{"id":"16392","type":"CID","arg1_id":"16380","arg2_id":"16381","normalized":[]},{"id":"16393","type":"CID","arg1_id":"16382","arg2_id":"16379","normalized":[]},{"id":"16394","type":"CID","arg1_id":"16382","arg2_id":"16381","normalized":[]},{"id":"16395","type":"CID","arg1_id":"16383","arg2_id":"16379","normalized":[]},{"id":"16396","type":"CID","arg1_id":"16383","arg2_id":"16381","normalized":[]}]}
{"id":"16397","document_id":"15531665","passages":[{"id":"16398","type":"title","text":["Does supplemental vitamin C increase cardiovascular disease risk in women with diabetes?"],"offsets":[[0,88]]},{"id":"16399","type":"abstract","text":["BACKGROUND: Vitamin C acts as a potent antioxidant; however, it can also be a prooxidant and glycate protein under certain circumstances in vitro. These observations led us to hypothesize that a high intake of vitamin C in diabetic persons might promote atherosclerosis. OBJECTIVE: The objective was to examine the relation between vitamin C intake and mortality from cardiovascular disease. DESIGN: We studied the relation between vitamin C intake and mortality from total cardiovascular disease (n = 281), coronary artery disease (n = 175), and stroke (n = 57) in 1923 postmenopausal women who reported being diabetic at baseline. Diet was assessed with a food-frequency questionnaire at baseline, and subjects initially free of coronary artery disease were prospectively followed for 15 y. RESULTS: After adjustment for cardiovascular disease risk factors, type of diabetes medication used, duration of diabetes, and intakes of folate, vitamin E, and beta-carotene, the adjusted relative risks of total cardiovascular disease mortality were 1.0, 0.97, 1.11, 1.47, and 1.84 (P for trend < 0.01) across quintiles of total vitamin C intake from food and supplements. Adjusted relative risks of coronary artery disease were 1.0, 0.81, 0.99, 1.26, and 1.91 (P for trend = 0.01) and of stroke were 1.0, 0.52, 1.23, 2.22, and 2.57 (P for trend < 0.01). When dietary and supplemental vitamin C were analyzed separately, only supplemental vitamin C showed a positive association with mortality endpoints. Vitamin C intake was unrelated to mortality from cardiovascular disease in the nondiabetic subjects at baseline. CONCLUSION: A high vitamin C intake from supplements is associated with an increased risk of cardiovascular disease mortality in postmenopausal women with diabetes."],"offsets":[[89,1865]]}],"entities":[{"id":"16400","type":"Chemical","text":["vitamin C"],"offsets":[[18,27]],"normalized":[{"db_name":"MESH","db_id":"D001205"}]},{"id":"16401","type":"Disease","text":["cardiovascular disease"],"offsets":[[37,59]],"normalized":[{"db_name":"MESH","db_id":"D002318"}]},{"id":"16402","type":"Disease","text":["diabetes"],"offsets":[[79,87]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"16403","type":"Chemical","text":["Vitamin C"],"offsets":[[101,110]],"normalized":[{"db_name":"MESH","db_id":"D001205"}]},{"id":"16404","type":"Chemical","text":["vitamin 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{"id":"16502","document_id":"12851669","passages":[{"id":"16503","type":"title","text":["Absolute and attributable risk of venous thromboembolism in women on combined cyproterone acetate and ethinylestradiol."],"offsets":[[0,119]]},{"id":"16504","type":"abstract","text":["OBJECTIVE: To achieve absolute risk estimates of venous thromboembolism (VTE) among women on cyproterone acetate plus ethinylestradiol (CPA\/EE), and among women on combined oral contraceptives (COCs). METHODS: From the Danish National Register of Patients (NRP), 1996 to 1998, the records of 1.1 million Danish women, ages 15 to 44 years, were searched for evidence of VTE. COC use was ascertained through mailed questionnaires. Sales statistics of COCs and CPA\/EE were provided through Danish Drug Statistics. RESULTS: During the time frame of the study, 330 women were found to have had VTE while on COCs. Of these women, 67 were on levonorgestrel-containing COCs. Eleven were on CPA\/EE. The corresponding absolute risk of VTE was 3.4 (range, 3.1-3.8) per 10 000 women years among the women on COCs, 4.2 (range, 3.2-5.2) per 10 000 women years among women on levonorgestrel-containing COCs, and 3.1 (range, 1.3-4.9) per 10 000 women years among the women on CPA\/EE. CONCLUSION: Our results suggest the absolute risk of VTE among Danish women on COCs is similar to that among women taking CPA\/EE."],"offsets":[[120,1217]]}],"entities":[{"id":"16505","type":"Disease","text":["venous thromboembolism"],"offsets":[[34,56]],"normalized":[{"db_name":"MESH","db_id":"D054556"}]},{"id":"16506","type":"Chemical","text":["cyproterone acetate"],"offsets":[[78,97]],"normalized":[{"db_name":"MESH","db_id":"D017373"}]},{"id":"16507","type":"Chemical","text":["ethinylestradiol"],"offsets":[[102,118]],"normalized":[{"db_name":"MESH","db_id":"D004997"}]},{"id":"16508","type":"Disease","text":["venous thromboembolism"],"offsets":[[169,191]],"normalized":[{"db_name":"MESH","db_id":"D054556"}]},{"id":"16509","type":"Disease","text":["VTE"],"offsets":[[193,196]],"normalized":[{"db_name":"MESH","db_id":"D054556"}]},{"id":"16510","type":"Chemical","text":["cyproterone 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{"id":"16600","document_id":"12842176","passages":[{"id":"16601","type":"title","text":["Effect of lindane on hepatic and brain cytochrome P450s and influence of P450 modulation in lindane induced neurotoxicity."],"offsets":[[0,122]]},{"id":"16602","type":"abstract","text":["Oral administration of lindane (2.5, 5, 10 and 15 mg\/kg, body weight) for 5 days was found to produce a dose-dependent increase in the activity of P450 dependent 7-ethoxyresorufin-O-deethylase (EROD), 7-pentoxyresorufin-O-dealkylase (PROD) and N-nitrosodimethylamine demethylase (NDMA-d) in rat brain and liver. A significant increase in the hepatic and brain P450 monooxygenases was also observed when the duration of exposure of low dose (2.5 mg\/kg) of lindane was increased from 5 days to 15 or 21 days. As observed with different doses, the magnitude of induction in the activity of P450 monooxygenases was several fold higher in liver microsomes when compared with the brain. Western blotting studies have indicated that the increase in the P450 enzymes could be due to the increase in the expression of P450 1A1\/1A2, 2B1\/2B2 and 2E1 isoenzymes. In vitro studies using organic inhibitors specific for individual P450 isoenzymes and antibody inhibition experiments have further demonstrated that the increase in the activity of PROD, EROD and NDMA-d are due to the increase in the levels of P450 2B1\/2B2, 1A1\/1A2 and 2E1 isoenzymes, respectively. Induction studies have further shown that while pretreatment of 3-methylcholanthrene (MC), an inducer of P4501A1\/1A2, did not produce any significant effect in the incidence of lindane induced convulsions, pretreatment with phenobarbital (PB), an inducer of P450 2B1\/2B2 or ethanol, an inducer of P450 2E1 catalysed reactions, significantly increased the incidence of lindane induced convulsions. Similarly, when the P450-mediated metabolism of lindane was blocked by cobalt chloride incidence of convulsions was increased in animals treated with lindane indicating that lindane per se or its metabolites formed by PB or ethanol inducible P450 isoenzymes are involved in its neurobehavioral toxicity."],"offsets":[[123,1974]]}],"entities":[{"id":"16603","type":"Chemical","text":["lindane"],"offsets":[[10,17]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"16604","type":"Chemical","text":["lindane"],"offsets":[[92,99]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"16605","type":"Disease","text":["neurotoxicity"],"offsets":[[108,121]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"16606","type":"Chemical","text":["lindane"],"offsets":[[146,153]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"16607","type":"Chemical","text":["N-nitrosodimethylamine"],"offsets":[[367,389]],"normalized":[{"db_name":"MESH","db_id":"D004128"}]},{"id":"16608","type":"Chemical","text":["NDMA"],"offsets":[[403,407]],"normalized":[{"db_name":"MESH","db_id":"D004128"}]},{"id":"16609","type":"Chemical","text":["lindane"],"offsets":[[578,585]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"16610","type":"Chemical","text":["NDMA"],"offsets":[[1170,1174]],"normalized":[{"db_name":"MESH","db_id":"D004128"}]},{"id":"16611","type":"Chemical","text":["3-methylcholanthrene"],"offsets":[[1338,1358]],"normalized":[{"db_name":"MESH","db_id":"D008748"}]},{"id":"16612","type":"Chemical","text":["MC"],"offsets":[[1360,1362]],"normalized":[{"db_name":"MESH","db_id":"D008748"}]},{"id":"16613","type":"Chemical","text":["lindane"],"offsets":[[1451,1458]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"16614","type":"Disease","text":["convulsions"],"offsets":[[1467,1478]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"16615","type":"Chemical","text":["phenobarbital"],"offsets":[[1498,1511]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"16616","type":"Chemical","text":["ethanol"],"offsets":[[1548,1555]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"16617","type":"Chemical","text":["lindane"],"offsets":[[1642,1649]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"16618","type":"Disease","text":["convulsions"],"offsets":[[1658,1669]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"16619","type":"Chemical","text":["lindane"],"offsets":[[1719,1726]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"16620","type":"Chemical","text":["cobalt chloride"],"offsets":[[1742,1757]],"normalized":[{"db_name":"MESH","db_id":"C018021"}]},{"id":"16621","type":"Disease","text":["convulsions"],"offsets":[[1771,1782]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"16622","type":"Chemical","text":["lindane"],"offsets":[[1821,1828]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"16623","type":"Chemical","text":["lindane"],"offsets":[[1845,1852]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"16624","type":"Chemical","text":["ethanol"],"offsets":[[1895,1902]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"16625","type":"Disease","text":["toxicity"],"offsets":[[1965,1973]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]}],"events":[],"coreferences":[],"relations":[{"id":"16626","type":"CID","arg1_id":"16603","arg2_id":"16614","normalized":[]},{"id":"16627","type":"CID","arg1_id":"16603","arg2_id":"16618","normalized":[]},{"id":"16628","type":"CID","arg1_id":"16603","arg2_id":"16621","normalized":[]},{"id":"16629","type":"CID","arg1_id":"16604","arg2_id":"16614","normalized":[]},{"id":"16630","type":"CID","arg1_id":"16604","arg2_id":"16618","normalized":[]},{"id":"16631","type":"CID","arg1_id":"16604","arg2_id":"16621","normalized":[]},{"id":"16632","type":"CID","arg1_id":"16606","arg2_id":"16614","normalized":[]},{"id":"16633","type":"CID","arg1_id":"16606","arg2_id":"16618","normalized":[]},{"id":"16634","type":"CID","arg1_id":"16606","arg2_id":"16621","normalized":[]},{"id":"16635","type":"CID","arg1_id":"16609","arg2_id":"16614","normalized":[]},{"id":"16636","type":"CID","arg1_id":"16609","arg2_id":"16618","normalized":[]},{"id":"16637","type":"CID","arg1_id":"16609","arg2_id":"16621","normalized":[]},{"id":"16638","type":"CID","arg1_id":"16613","arg2_id":"16614","normalized":[]},{"id":"16639","type":"CID","arg1_id":"16613","arg2_id":"16618","normalized":[]},{"id":"16640","type":"CID","arg1_id":"16613","arg2_id":"16621","normalized":[]},{"id":"16641","type":"CID","arg1_id":"16617","arg2_id":"16614","normalized":[]},{"id":"16642","type":"CID","arg1_id":"16617","arg2_id":"16618","normalized":[]},{"id":"16643","type":"CID","arg1_id":"16617","arg2_id":"16621","normalized":[]},{"id":"16644","type":"CID","arg1_id":"16619","arg2_id":"16614","normalized":[]},{"id":"16645","type":"CID","arg1_id":"16619","arg2_id":"16618","normalized":[]},{"id":"16646","type":"CID","arg1_id":"16619","arg2_id":"16621","normalized":[]},{"id":"16647","type":"CID","arg1_id":"16622","arg2_id":"16614","normalized":[]},{"id":"16648","type":"CID","arg1_id":"16622","arg2_id":"16618","normalized":[]},{"id":"16649","type":"CID","arg1_id":"16622","arg2_id":"16621","normalized":[]},{"id":"16650","type":"CID","arg1_id":"16623","arg2_id":"16614","normalized":[]},{"id":"16651","type":"CID","arg1_id":"16623","arg2_id":"16618","normalized":[]},{"id":"16652","type":"CID","arg1_id":"16623","arg2_id":"16621","normalized":[]}]}
{"id":"16653","document_id":"12745515","passages":[{"id":"16654","type":"title","text":["Seizure associated with sleep deprivation and sustained-release bupropion."],"offsets":[[0,74]]},{"id":"16655","type":"abstract","text":["This case report describes a generalized seizure associated with sustained-release bupropion use and sleep deprivation. The subject, a 31-year-old female smoker, was participating in a clinical trial evaluating an investigational medication for smoking cessation that used sustained-release bupropion as an active control. After 5 weeks of bupropion use, the subject experienced a generalized tonic clonic seizure after staying up nearly all night packing and moving to a new residence. The patient had no other risk factors for seizures. We suggest that sleep deprivation may add to the risk of bupropion-associated seizures."],"offsets":[[75,701]]}],"entities":[{"id":"16656","type":"Disease","text":["Seizure"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"16657","type":"Disease","text":["sleep deprivation"],"offsets":[[24,41]],"normalized":[{"db_name":"MESH","db_id":"D012892"}]},{"id":"16658","type":"Chemical","text":["bupropion"],"offsets":[[64,73]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"16659","type":"Disease","text":["seizure"],"offsets":[[116,123]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"16660","type":"Chemical","text":["bupropion"],"offsets":[[158,167]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"16661","type":"Disease","text":["sleep deprivation"],"offsets":[[176,193]],"normalized":[{"db_name":"MESH","db_id":"D012892"}]},{"id":"16662","type":"Chemical","text":["bupropion"],"offsets":[[366,375]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"16663","type":"Chemical","text":["bupropion"],"offsets":[[415,424]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"16664","type":"Disease","text":["seizure"],"offsets":[[481,488]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"16665","type":"Disease","text":["seizures"],"offsets":[[604,612]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"16666","type":"Disease","text":["sleep deprivation"],"offsets":[[630,647]],"normalized":[{"db_name":"MESH","db_id":"D012892"}]},{"id":"16667","type":"Chemical","text":["bupropion"],"offsets":[[671,680]],"normalized":[{"db_name":"MESH","db_id":"D016642"}]},{"id":"16668","type":"Disease","text":["seizures"],"offsets":[[692,700]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]}],"events":[],"coreferences":[],"relations":[{"id":"16669","type":"CID","arg1_id":"16658","arg2_id":"16656","normalized":[]},{"id":"16670","type":"CID","arg1_id":"16658","arg2_id":"16659","normalized":[]},{"id":"16671","type":"CID","arg1_id":"16658","arg2_id":"16664","normalized":[]},{"id":"16672","type":"CID","arg1_id":"16658","arg2_id":"16665","normalized":[]},{"id":"16673","type":"CID","arg1_id":"16658","arg2_id":"16668","normalized":[]},{"id":"16674","type":"CID","arg1_id":"16660","arg2_id":"16656","normalized":[]},{"id":"16675","type":"CID","arg1_id":"16660","arg2_id":"16659","normalized":[]},{"id":"16676","type":"CID","arg1_id":"16660","arg2_id":"16664","normalized":[]},{"id":"16677","type":"CID","arg1_id":"16660","arg2_id":"16665","normalized":[]},{"id":"16678","type":"CID","arg1_id":"16660","arg2_id":"16668","normalized":[]},{"id":"16679","type":"CID","arg1_id":"16662","arg2_id":"16656","normalized":[]},{"id":"16680","type":"CID","arg1_id":"16662","arg2_id":"16659","normalized":[]},{"id":"16681","type":"CID","arg1_id":"16662","arg2_id":"16664","normalized":[]},{"id":"16682","type":"CID","arg1_id":"16662","arg2_id":"16665","normalized":[]},{"id":"16683","type":"CID","arg1_id":"16662","arg2_id":"16668","normalized":[]},{"id":"16684","type":"CID","arg1_id":"16663","arg2_id":"16656","normalized":[]},{"id":"16685","type":"CID","arg1_id":"16663","arg2_id":"16659","normalized":[]},{"id":"16686","type":"CID","arg1_id":"16663","arg2_id":"16664","normalized":[]},{"id":"16687","type":"CID","arg1_id":"16663","arg2_id":"16665","normalized":[]},{"id":"16688","type":"CID","arg1_id":"16663","arg2_id":"16668","normalized":[]},{"id":"16689","type":"CID","arg1_id":"16667","arg2_id":"16656","normalized":[]},{"id":"16690","type":"CID","arg1_id":"16667","arg2_id":"16659","normalized":[]},{"id":"16691","type":"CID","arg1_id":"16667","arg2_id":"16664","normalized":[]},{"id":"16692","type":"CID","arg1_id":"16667","arg2_id":"16665","normalized":[]},{"id":"16693","type":"CID","arg1_id":"16667","arg2_id":"16668","normalized":[]}]}
{"id":"16694","document_id":"12571256","passages":[{"id":"16695","type":"title","text":["Nephrotoxic effects in high-risk patients undergoing angiography."],"offsets":[[0,65]]},{"id":"16696","type":"abstract","text":["BACKGROUND: The use of iodinated contrast medium can result in nephropathy. Whether iso-osmolar contrast medium is less nephrotoxic than low-osmolar contrast medium in high-risk patients is uncertain. METHODS: We conducted a randomized, double-blind, prospective, multicenter study comparing the nephrotoxic effects of an iso-osmolar, dimeric, nonionic contrast medium, iodixanol, with those of a low-osmolar, nonionic, monomeric contrast medium, iohexol. The study involved 129 patients with diabetes with serum creatinine concentrations of 1.5 to 3.5 mg per deciliter who underwent coronary or aortofemoral angiography. The primary end point was the peak increase from base line in the creatinine concentration during the three days after angiography. Other end points were an increase in the creatinine concentration of 0.5 mg per deciliter or more, an increase of 1.0 mg per deciliter or more, and a change in the creatinine concentration from day 0 to day 7. RESULTS: The creatinine concentration increased significantly less in patients who received iodixanol. From day 0 to day 3, the mean peak increase in creatinine was 0.13 mg per deciliter in the iodixanol group and 0.55 mg per deciliter in the iohexol group (P=0.001; the increase with iodixanol minus the increase with iohexol, -0.42 mg per deciliter [95 percent confidence interval, -0.73 to -0.22]). Two of the 64 patients in the iodixanol group (3 percent) had an increase in the creatinine concentration of 0.5 mg per deciliter or more, as compared with 17 of the 65 patients in the iohexol group (26 percent) (P=0.002; odds ratio for such an increase in the iodixanol group, 0.09 [95 percent confidence interval, 0.02 to 0.41]). No patient receiving iodixanol had an increase of 1.0 mg per deciliter or more, but 10 patients in the iohexol group (15 percent) did. The mean change in the creatinine concentration from day 0 to day 7 was 0.07 mg per deciliter in the iodixanol group and 0.24 mg per deciliter in the iohexol group (P=0.003; value in the iodixanol group minus the value in the iohexol group, -0.17 mg per deciliter [95 percent confidence interval, -0.34 to -0.07]). CONCLUSIONS: Nephropathy induced by contrast medium may be less likely to develop in high-risk patients when iodixanol is used rather than a low-osmolar, nonionic contrast medium."],"offsets":[[66,2393]]}],"entities":[{"id":"16697","type":"Disease","text":["Nephrotoxic"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"16698","type":"Disease","text":["nephropathy"],"offsets":[[129,140]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"16699","type":"Disease","text":["nephrotoxic"],"offsets":[[186,197]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"16700","type":"Disease","text":["nephrotoxic"],"offsets":[[362,373]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"16701","type":"Chemical","text":["iodixanol"],"offsets":[[436,445]],"normalized":[{"db_name":"MESH","db_id":"C044834"}]},{"id":"16702","type":"Chemical","text":["iohexol"],"offsets":[[513,520]],"normalized":[{"db_name":"MESH","db_id":"D007472"}]},{"id":"16703","type":"Disease","text":["diabetes"],"offsets":[[559,567]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"16704","type":"Chemical","text":["creatinine"],"offsets":[[579,589]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"16705","type":"Chemical","text":["creatinine"],"offsets":[[754,764]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"16706","type":"Chemical","text":["creatinine"],"offsets":[[861,871]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"16707","type":"Chemical","text":["creatinine"],"offsets":[[984,994]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"16708","type":"Chemical","text":["creatinine"],"offsets":[[1043,1053]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"16709","type":"Chemical","text":["iodixanol"],"offsets":[[1122,1131]],"normalized":[{"db_name":"MESH","db_id":"C044834"}]},{"id":"16710","type":"Chemical","text":["creatinine"],"offsets":[[1180,1190]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"16711","type":"Chemical","text":["iodixanol"],"offsets":[[1224,1233]],"normalized":[{"db_name":"MESH","db_id":"C044834"}]},{"id":"16712","type":"Chemical","text":["iohexol"],"offsets":[[1273,1280]],"normalized":[{"db_name":"MESH","db_id":"D007472"}]},{"id":"16713","type":"Chemical","text":["iodixanol"],"offsets":[[1315,1324]],"normalized":[{"db_name":"MESH","db_id":"C044834"}]},{"id":"16714","type":"Chemical","text":["iohexol"],"offsets":[[1349,1356]],"normalized":[{"db_name":"MESH","db_id":"D007472"}]},{"id":"16715","type":"Chemical","text":["iodixanol"],"offsets":[[1462,1471]],"normalized":[{"db_name":"MESH","db_id":"C044834"}]},{"id":"16716","type":"Chemical","text":["creatinine"],"offsets":[[1513,1523]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"16717","type":"Chemical","text":["iohexol"],"offsets":[[1617,1624]],"normalized":[{"db_name":"MESH","db_id":"D007472"}]},{"id":"16718","type":"Chemical","text":["iodixanol"],"offsets":[[1693,1702]],"normalized":[{"db_name":"MESH","db_id":"C044834"}]},{"id":"16719","type":"Chemical","text":["iodixanol"],"offsets":[[1785,1794]],"normalized":[{"db_name":"MESH","db_id":"C044834"}]},{"id":"16720","type":"Chemical","text":["iohexol"],"offsets":[[1867,1874]],"normalized":[{"db_name":"MESH","db_id":"D007472"}]},{"id":"16721","type":"Chemical","text":["creatinine"],"offsets":[[1922,1932]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"16722","type":"Chemical","text":["iodixanol"],"offsets":[[2000,2009]],"normalized":[{"db_name":"MESH","db_id":"C044834"}]},{"id":"16723","type":"Chemical","text":["iohexol"],"offsets":[[2049,2056]],"normalized":[{"db_name":"MESH","db_id":"D007472"}]},{"id":"16724","type":"Chemical","text":["iodixanol"],"offsets":[[2086,2095]],"normalized":[{"db_name":"MESH","db_id":"C044834"}]},{"id":"16725","type":"Chemical","text":["iohexol"],"offsets":[[2125,2132]],"normalized":[{"db_name":"MESH","db_id":"D007472"}]},{"id":"16726","type":"Disease","text":["Nephropathy"],"offsets":[[2227,2238]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"16727","type":"Chemical","text":["iodixanol"],"offsets":[[2323,2332]],"normalized":[{"db_name":"MESH","db_id":"C044834"}]}],"events":[],"coreferences":[],"relations":[{"id":"16728","type":"CID","arg1_id":"16702","arg2_id":"16697","normalized":[]},{"id":"16729","type":"CID","arg1_id":"16702","arg2_id":"16698","normalized":[]},{"id":"16730","type":"CID","arg1_id":"16702","arg2_id":"16699","normalized":[]},{"id":"16731","type":"CID","arg1_id":"16702","arg2_id":"16700","normalized":[]},{"id":"16732","type":"CID","arg1_id":"16702","arg2_id":"16726","normalized":[]},{"id":"16733","type":"CID","arg1_id":"16712","arg2_id":"16697","normalized":[]},{"id":"16734","type":"CID","arg1_id":"16712","arg2_id":"16698","normalized":[]},{"id":"16735","type":"CID","arg1_id":"16712","arg2_id":"16699","normalized":[]},{"id":"16736","type":"CID","arg1_id":"16712","arg2_id":"16700","normalized":[]},{"id":"16737","type":"CID","arg1_id":"16712","arg2_id":"16726","normalized":[]},{"id":"16738","type":"CID","arg1_id":"16714","arg2_id":"16697","normalized":[]},{"id":"16739","type":"CID","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{"id":"16763","document_id":"9514561","passages":[{"id":"16764","type":"title","text":["Experimental cranial pain elicited by capsaicin: a PET study."],"offsets":[[0,61]]},{"id":"16765","type":"abstract","text":["Using a positron emission tomography (PET) study it was shown recently that in migraine without aura certain areas in the brain stem were activated during the headache state, but not in the headache free interval. It was suggested that this brain stem activation is inherent to the migraine attack itself and represents the so called 'migraine generator'. To test this hypothesis we performed an experimental pain study in seven healthy volunteers, using the same positioning in the PET scanner as in the migraine patients. A small amount of capsaicin was administered subcutaneously in the right forehead to evoke a burning painful sensation in the first division of the trigeminal nerve. Increases of regional cerebral blood flow (rCBF) were found bilaterally in the insula, in the anterior cingulate cortex, the cavernous sinus and the cerebellum. Using the same stereotactic space limits as in the above mentioned migraine study no brain stem activation was found in the acute pain state compared to the pain free state. The increase of activation in the region of the cavernous sinus however, suggests that this structure is more likely to be involved in trigeminal transmitted pain as such, rather than in a specific type of headache as was suggested for cluster headache."],"offsets":[[62,1340]]}],"entities":[{"id":"16766","type":"Disease","text":["pain"],"offsets":[[21,25]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"16767","type":"Chemical","text":["capsaicin"],"offsets":[[38,47]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"16768","type":"Disease","text":["migraine"],"offsets":[[141,149]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"16769","type":"Disease","text":["headache"],"offsets":[[221,229]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"16770","type":"Disease","text":["headache"],"offsets":[[252,260]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"16771","type":"Disease","text":["migraine"],"offsets":[[344,352]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"16772","type":"Disease","text":["migraine"],"offsets":[[397,405]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"16773","type":"Disease","text":["pain"],"offsets":[[471,475]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"16774","type":"Disease","text":["migraine"],"offsets":[[567,575]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"16775","type":"Chemical","text":["capsaicin"],"offsets":[[604,613]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"16776","type":"Disease","text":["painful"],"offsets":[[687,694]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"16777","type":"Disease","text":["migraine"],"offsets":[[980,988]],"normalized":[{"db_name":"MESH","db_id":"D008881"}]},{"id":"16778","type":"Disease","text":["pain"],"offsets":[[1043,1047]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"16779","type":"Disease","text":["pain"],"offsets":[[1070,1074]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"16780","type":"Disease","text":["pain"],"offsets":[[1245,1249]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"16781","type":"Disease","text":["headache"],"offsets":[[1293,1301]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"16782","type":"Disease","text":["cluster headache"],"offsets":[[1323,1339]],"normalized":[{"db_name":"MESH","db_id":"D003027"}]}],"events":[],"coreferences":[],"relations":[{"id":"16783","type":"CID","arg1_id":"16767","arg2_id":"16766","normalized":[]},{"id":"16784","type":"CID","arg1_id":"16767","arg2_id":"16773","normalized":[]},{"id":"16785","type":"CID","arg1_id":"16767","arg2_id":"16776","normalized":[]},{"id":"16786","type":"CID","arg1_id":"16767","arg2_id":"16778","normalized":[]},{"id":"16787","type":"CID","arg1_id":"16767","arg2_id":"16779","normalized":[]},{"id":"16788","type":"CID","arg1_id":"16767","arg2_id":"16780","normalized":[]},{"id":"16789","type":"CID","arg1_id":"16775","arg2_id":"16766","normalized":[]},{"id":"16790","type":"CID","arg1_id":"16775","arg2_id":"16773","normalized":[]},{"id":"16791","type":"CID","arg1_id":"16775","arg2_id":"16776","normalized":[]},{"id":"16792","type":"CID","arg1_id":"16775","arg2_id":"16778","normalized":[]},{"id":"16793","type":"CID","arg1_id":"16775","arg2_id":"16779","normalized":[]},{"id":"16794","type":"CID","arg1_id":"16775","arg2_id":"16780","normalized":[]}]}
{"id":"16795","document_id":"9165568","passages":[{"id":"16796","type":"title","text":["Neuroleptic malignant syndrome with risperidone."],"offsets":[[0,48]]},{"id":"16797","type":"abstract","text":["Neuroleptic malignant syndrome is thought to be a result of dopamine D2 receptor blockade in the striatum of the basal ganglia. Risperidone, a benzisoxazole derivative antipsychotic, has high serotonin 5-HT2 receptor blockade and dose-related D2 receptor blockade. The high ratio is believed to impart the low frequency of extrapyramidal symptoms with risperidone at low dosages. With this low frequency of extrapyramidal symptoms, it was thought the frequency of neuroleptic malignant syndrome might also be lowered. A 73-year-old woman developed neuroleptic malignant syndrome after monotherapy with risperidone. The syndrome reversed after discontinuing risperidone and starting treatment with dantrolene and bromocriptine. It appears that the protection from extrapyramidal side effects observed with risperidone does not ensure protection from neuroleptic malignant syndrome."],"offsets":[[49,929]]}],"entities":[{"id":"16798","type":"Disease","text":["Neuroleptic malignant syndrome"],"offsets":[[0,30]],"normalized":[{"db_name":"MESH","db_id":"D009459"}]},{"id":"16799","type":"Chemical","text":["risperidone"],"offsets":[[36,47]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"16800","type":"Disease","text":["Neuroleptic malignant 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{"id":"16846","document_id":"9154656","passages":[{"id":"16847","type":"title","text":["Hepatic and extrahepatic angiotensinogen gene expression in rats with acute nephrotic syndrome."],"offsets":[[0,95]]},{"id":"16848","type":"abstract","text":["Plasma concentration and urine excretion of the renin-angiotensin system proteins are altered in rats with nephrotic syndrome (NS). In this work the messenger ribonucleic acid (mRNA) levels of angiotensinogen (Ao) were analyzed with the slot-blot hybridization technique in liver and other extrahepatic tissues: kidney, heart, brain, and adrenal gland from control, nephrotic, and pair-fed (PF) rats. NS was induced by a single injection of puromycin amino-nucleoside (PAN). Although a great urinary excretion and half-normal plasma levels of Ao were observed on day 6 after PAN injection, when NS was clearly established, hepatic Ao mRNA levels did not change. Furthermore, the Ao mRNA levels did not change in any of the extrahepatic tissues studied on day 6, nor did its hepatic levels at days 1, 3, 5, or 7 after PAN injection. These data suggest that the hepatic and extrahepatic Ao mRNA levels are unaltered during the development of the acute NS induced by PAN."],"offsets":[[96,1064]]}],"entities":[{"id":"16849","type":"Disease","text":["nephrotic syndrome"],"offsets":[[76,94]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]},{"id":"16850","type":"Chemical","text":["angiotensin"],"offsets":[[150,161]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"16851","type":"Disease","text":["nephrotic syndrome"],"offsets":[[203,221]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]},{"id":"16852","type":"Disease","text":["NS"],"offsets":[[223,225]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]},{"id":"16853","type":"Disease","text":["nephrotic"],"offsets":[[462,471]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]},{"id":"16854","type":"Disease","text":["NS"],"offsets":[[497,499]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]},{"id":"16855","type":"Chemical","text":["puromycin amino-nucleoside"],"offsets":[[537,563]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"16856","type":"Chemical","text":["PAN"],"offsets":[[565,568]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"16857","type":"Chemical","text":["PAN"],"offsets":[[671,674]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"16858","type":"Disease","text":["NS"],"offsets":[[691,693]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]},{"id":"16859","type":"Chemical","text":["PAN"],"offsets":[[913,916]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"16860","type":"Disease","text":["NS"],"offsets":[[1046,1048]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]},{"id":"16861","type":"Chemical","text":["PAN"],"offsets":[[1060,1063]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]}],"events":[],"coreferences":[],"relations":[{"id":"16862","type":"CID","arg1_id":"16855","arg2_id":"16849","normalized":[]},{"id":"16863","type":"CID","arg1_id":"16855","arg2_id":"16851","normalized":[]},{"id":"16864","type":"CID","arg1_id":"16855","arg2_id":"16852","normalized":[]},{"id":"16865","type":"CID","arg1_id":"16855","arg2_id":"16853","normalized":[]},{"id":"16866","type":"CID","arg1_id":"16855","arg2_id":"16854","normalized":[]},{"id":"16867","type":"CID","arg1_id":"16855","arg2_id":"16858","normalized":[]},{"id":"16868","type":"CID","arg1_id":"16855","arg2_id":"16860","normalized":[]},{"id":"16869","type":"CID","arg1_id":"16856","arg2_id":"16849","normalized":[]},{"id":"16870","type":"CID","arg1_id":"16856","arg2_id":"16851","normalized":[]},{"id":"16871","type":"CID","arg1_id":"16856","arg2_id":"16852","normalized":[]},{"id":"16872","type":"CID","arg1_id":"16856","arg2_id":"16853","normalized":[]},{"id":"16873","type":"CID","arg1_id":"16856","arg2_id":"16854","normalized":[]},{"id":"16874","type":"CID","arg1_id":"16856","arg2_id":"16858","normalized":[]},{"id":"16875","type":"CID","arg1_id":"16856","arg2_id":"16860","normalized":[]},{"id":"16876","type":"CID","arg1_id":"16857","arg2_id":"16849","normalized":[]},{"id":"16877","type":"CID","arg1_id":"16857","arg2_id":"16851","normalized":[]},{"id":"16878","type":"CID","arg1_id":"16857","arg2_id":"16852","normalized":[]},{"id":"16879","type":"CID","arg1_id":"16857","arg2_id":"16853","normalized":[]},{"id":"16880","type":"CID","arg1_id":"16857","arg2_id":"16854","normalized":[]},{"id":"16881","type":"CID","arg1_id":"16857","arg2_id":"16858","normalized":[]},{"id":"16882","type":"CID","arg1_id":"16857","arg2_id":"16860","normalized":[]},{"id":"16883","type":"CID","arg1_id":"16859","arg2_id":"16849","normalized":[]},{"id":"16884","type":"CID","arg1_id":"16859","arg2_id":"16851","normalized":[]},{"id":"16885","type":"CID","arg1_id":"16859","arg2_id":"16852","normalized":[]},{"id":"16886","type":"CID","arg1_id":"16859","arg2_id":"16853","normalized":[]},{"id":"16887","type":"CID","arg1_id":"16859","arg2_id":"16854","normalized":[]},{"id":"16888","type":"CID","arg1_id":"16859","arg2_id":"16858","normalized":[]},{"id":"16889","type":"CID","arg1_id":"16859","arg2_id":"16860","normalized":[]},{"id":"16890","type":"CID","arg1_id":"16861","arg2_id":"16849","normalized":[]},{"id":"16891","type":"CID","arg1_id":"16861","arg2_id":"16851","normalized":[]},{"id":"16892","type":"CID","arg1_id":"16861","arg2_id":"16852","normalized":[]},{"id":"16893","type":"CID","arg1_id":"16861","arg2_id":"16853","normalized":[]},{"id":"16894","type":"CID","arg1_id":"16861","arg2_id":"16854","normalized":[]},{"id":"16895","type":"CID","arg1_id":"16861","arg2_id":"16858","normalized":[]},{"id":"16896","type":"CID","arg1_id":"16861","arg2_id":"16860","normalized":[]}]}
{"id":"16897","document_id":"8911359","passages":[{"id":"16898","type":"title","text":["Cyclophosphamide associated bladder cancer--a highly aggressive disease: analysis of 12 cases."],"offsets":[[0,94]]},{"id":"16899","type":"abstract","text":["PURPOSE: We gained knowledge of the etiology, treatment and prevention of cyclophosphamide associated urothelial cancer. MATERIALS AND METHODS: The medical records of 6 men and 6 women (mean age 55 years) with cyclophosphamide associated bladder cancer were reviewed. RESULTS: All tumors were grade 3 or 4 transitional cell carcinoma. Of the 5 patients initially treated with endoscopic resection alone only 1 is alive without disease. Of the 6 patients who underwent early cystectomy 4 were alive at 24 to 111 months. The remaining patient with extensive cancer underwent partial cystectomy for palliation and died 3 months later. CONCLUSIONS: Cyclophosphamide associated bladder tumor is an aggressive disease. However, long-term survival is possible when radical cystectomy is performed for bladder tumors with any sign of invasion and for recurrent high grade disease, even when noninvasive."],"offsets":[[95,990]]}],"entities":[{"id":"16900","type":"Chemical","text":["Cyclophosphamide"],"offsets":[[0,16]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"16901","type":"Disease","text":["bladder cancer"],"offsets":[[28,42]],"normalized":[{"db_name":"MESH","db_id":"D001749"}]},{"id":"16902","type":"Chemical","text":["cyclophosphamide"],"offsets":[[169,185]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"16903","type":"Disease","text":["urothelial cancer"],"offsets":[[197,214]],"normalized":[{"db_name":"MESH","db_id":"D014523"}]},{"id":"16904","type":"Chemical","text":["cyclophosphamide"],"offsets":[[305,321]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"16905","type":"Disease","text":["bladder cancer"],"offsets":[[333,347]],"normalized":[{"db_name":"MESH","db_id":"D001749"}]},{"id":"16906","type":"Disease","text":["tumors"],"offsets":[[376,382]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"16907","type":"Disease","text":["carcinoma"],"offsets":[[419,428]],"normalized":[{"db_name":"MESH","db_id":"D002277"}]},{"id":"16908","type":"Disease","text":["cancer"],"offsets":[[651,657]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"16909","type":"Chemical","text":["Cyclophosphamide"],"offsets":[[740,756]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"16910","type":"Disease","text":["bladder tumor"],"offsets":[[768,781]],"normalized":[{"db_name":"MESH","db_id":"D001749"}]},{"id":"16911","type":"Disease","text":["bladder tumors"],"offsets":[[889,903]],"normalized":[{"db_name":"MESH","db_id":"D001749"}]}],"events":[],"coreferences":[],"relations":[{"id":"16912","type":"CID","arg1_id":"16900","arg2_id":"16901","normalized":[]},{"id":"16913","type":"CID","arg1_id":"16900","arg2_id":"16905","normalized":[]},{"id":"16914","type":"CID","arg1_id":"16900","arg2_id":"16910","normalized":[]},{"id":"16915","type":"CID","arg1_id":"16900","arg2_id":"16911","normalized":[]},{"id":"16916","type":"CID","arg1_id":"16902","arg2_id":"16901","normalized":[]},{"id":"16917","type":"CID","arg1_id":"16902","arg2_id":"16905","normalized":[]},{"id":"16918","type":"CID","arg1_id":"16902","arg2_id":"16910","normalized":[]},{"id":"16919","type":"CID","arg1_id":"16902","arg2_id":"16911","normalized":[]},{"id":"16920","type":"CID","arg1_id":"16904","arg2_id":"16901","normalized":[]},{"id":"16921","type":"CID","arg1_id":"16904","arg2_id":"16905","normalized":[]},{"id":"16922","type":"CID","arg1_id":"16904","arg2_id":"16910","normalized":[]},{"id":"16923","type":"CID","arg1_id":"16904","arg2_id":"16911","normalized":[]},{"id":"16924","type":"CID","arg1_id":"16909","arg2_id":"16901","normalized":[]},{"id":"16925","type":"CID","arg1_id":"16909","arg2_id":"16905","normalized":[]},{"id":"16926","type":"CID","arg1_id":"16909","arg2_id":"16910","normalized":[]},{"id":"16927","type":"CID","arg1_id":"16909","arg2_id":"16911","normalized":[]}]}
{"id":"16928","document_id":"8686832","passages":[{"id":"16929","type":"title","text":["Leg and back pain after spinal anaesthesia involving hyperbaric 5% lignocaine."],"offsets":[[0,78]]},{"id":"16930","type":"abstract","text":["Fifty-four patients, aged 27-90 years, who were given lignocaine 5% in 6.8% glucose solution for spinal anaesthesia were studied. Thirteen of these patients experienced pain in the legs and\/or back after recovery from anaesthesia. The patients affected were younger (p < 0.05) and the site of the dural puncture was higher (p < 0.01) than those individuals without pain. Five of the 13 patients (38%) with pain and seven of the 41 patients (17%) without pain admitted to a high alcohol intake, which might be a contributing factor. Leg and\/or back pain is associated with the intrathecal use of hyperbaric 5% lignocaine."],"offsets":[[79,699]]}],"entities":[{"id":"16931","type":"Disease","text":["Leg and back pain"],"offsets":[[0,17]],"normalized":[{"db_name":"MESH","db_id":"D001416"}]},{"id":"16932","type":"Chemical","text":["lignocaine"],"offsets":[[67,77]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"16933","type":"Chemical","text":["lignocaine"],"offsets":[[133,143]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"16934","type":"Chemical","text":["glucose"],"offsets":[[155,162]],"normalized":[{"db_name":"MESH","db_id":"D005947"}]},{"id":"16935","type":"Disease","text":["pain in the legs and\/or back"],"offsets":[[248,276]],"normalized":[{"db_name":"MESH","db_id":"D001416"}]},{"id":"16936","type":"Disease","text":["pain"],"offsets":[[444,448]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"16937","type":"Disease","text":["pain"],"offsets":[[485,489]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"16938","type":"Disease","text":["pain"],"offsets":[[533,537]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"16939","type":"Chemical","text":["alcohol"],"offsets":[[557,564]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"16940","type":"Disease","text":["Leg and\/or back pain"],"offsets":[[611,631]],"normalized":[{"db_name":"MESH","db_id":"D001416"}]},{"id":"16941","type":"Chemical","text":["lignocaine"],"offsets":[[688,698]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]}],"events":[],"coreferences":[],"relations":[{"id":"16942","type":"CID","arg1_id":"16932","arg2_id":"16931","normalized":[]},{"id":"16943","type":"CID","arg1_id":"16932","arg2_id":"16935","normalized":[]},{"id":"16944","type":"CID","arg1_id":"16932","arg2_id":"16940","normalized":[]},{"id":"16945","type":"CID","arg1_id":"16933","arg2_id":"16931","normalized":[]},{"id":"16946","type":"CID","arg1_id":"16933","arg2_id":"16935","normalized":[]},{"id":"16947","type":"CID","arg1_id":"16933","arg2_id":"16940","normalized":[]},{"id":"16948","type":"CID","arg1_id":"16941","arg2_id":"16931","normalized":[]},{"id":"16949","type":"CID","arg1_id":"16941","arg2_id":"16935","normalized":[]},{"id":"16950","type":"CID","arg1_id":"16941","arg2_id":"16940","normalized":[]}]}
{"id":"16951","document_id":"8607407","passages":[{"id":"16952","type":"title","text":["Acute blood pressure elevations with caffeine in men with borderline systemic hypertension."],"offsets":[[0,91]]},{"id":"16953","type":"abstract","text":["Whether the vasoconstrictive actions of caffeine are enhanced in hypertensive persons has not been demonstrated. Thus, caffeine (3.3 mg\/kg) versus placebo was tested in 48 healthy men (aged 20 to 35 years) selected after screening on 2 separate occasions. Borderline hypertensive men (n = 24) were selected with screening systolic blood pressure (BP) of 140 to 160 mm Hg and\/or diastolic BP 90 to 99 mm Hg. Low-risk controls (n = 24) reported no parental history of hypertension and had screening BP < 130\/85 mm Hg. Participants were then tested on 2 occasions after 12-hour abstinence from caffeine in each of 2 protocols; this required a total of 4 laboratory visits. Caffeine-induced changes in diastolic BP were 2 to 3 times larger in borderline subjects than in controls (+8.4 vs +3.8 mm Hg, p < 0.0001), and were attributable to larger changes in impedance-derived measures of systemic vascular resistance (+135 vs +45 dynes.s.cm-5, p < 0.004). These findings were consistent and reached significance in both protocols. The percentage of borderline subjects in whom diastolic BP changes exceeded the median control response was 96%. Consequently, whereas all participants exhibited normotensive levels during the resting predrug baseline, 33% of borderline subjects achieved hypertensive BP levels after caffeine ingestion. Thus, in borderline hypertensive men, exaggerated responses to caffeine were: selective for diastolic BP, consistent with greater vasoconstriction, replicated in 2 protocols, and representative of nearly all borderline hypertensives. We suspect that the potential for caffeine to stabilize high resistance states in susceptible persons suggests that its use may facilitate their disease progression, as well as hinder accurate diagnosis and treatment."],"offsets":[[92,1873]]}],"entities":[{"id":"16954","type":"Chemical","text":["caffeine"],"offsets":[[37,45]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"16955","type":"Disease","text":["hypertension"],"offsets":[[78,90]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"16956","type":"Chemical","text":["caffeine"],"offsets":[[132,140]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"16957","type":"Disease","text":["hypertensive"],"offsets":[[157,169]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"16958","type":"Chemical","text":["caffeine"],"offsets":[[211,219]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"16959","type":"Disease","text":["hypertensive"],"offsets":[[359,371]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"16960","type":"Disease","text":["hypertension"],"offsets":[[558,570]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"16961","type":"Chemical","text":["caffeine"],"offsets":[[683,691]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"16962","type":"Chemical","text":["Caffeine"],"offsets":[[762,770]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"16963","type":"Disease","text":["hypertensive"],"offsets":[[1373,1385]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"16964","type":"Chemical","text":["caffeine"],"offsets":[[1402,1410]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"16965","type":"Disease","text":["hypertensive"],"offsets":[[1442,1454]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"16966","type":"Chemical","text":["caffeine"],"offsets":[[1485,1493]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]},{"id":"16967","type":"Disease","text":["hypertensives"],"offsets":[[1641,1654]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"16968","type":"Chemical","text":["caffeine"],"offsets":[[1690,1698]],"normalized":[{"db_name":"MESH","db_id":"D002110"}]}],"events":[],"coreferences":[],"relations":[{"id":"16969","type":"CID","arg1_id":"16954","arg2_id":"16955","normalized":[]},{"id":"16970","type":"CID","arg1_id":"16954","arg2_id":"16957","normalized":[]},{"id":"16971","type":"CID","arg1_id":"16954","arg2_id":"16959","normalized":[]},{"id":"16972","type":"CID","arg1_id":"16954","arg2_id":"16960","normalized":[]},{"id":"16973","type":"CID","arg1_id":"16954","arg2_id":"16963","normalized":[]},{"id":"16974","type":"CID","arg1_id":"16954","arg2_id":"16965","normalized":[]},{"id":"16975","type":"CID","arg1_id":"16954","arg2_id":"16967","normalized":[]},{"id":"16976","type":"CID","arg1_id":"16956","arg2_id":"16955","normalized":[]},{"id":"16977","type":"CID","arg1_id":"16956","arg2_id":"16957","normalized":[]},{"id":"16978","type":"CID","arg1_id":"16956","arg2_id":"16959","normalized":[]},{"id":"16979","type":"CID","arg1_id":"16956","arg2_id":"16960","normalized":[]},{"id":"16980","type":"CID","arg1_id":"16956","arg2_id":"16963","normalized":[]},{"id":"16981","type":"CID","arg1_id":"16956","arg2_id":"16965","normalized":[]},{"id":"16982","type":"CID","arg1_id":"16956","arg2_id":"16967","normalized":[]},{"id":"16983","type":"CID","arg1_id":"16958","arg2_id":"16955","normalized":[]},{"id":"16984","type":"CID","arg1_id":"16958","arg2_id":"16957","normalized":[]},{"id":"16985","type":"CID","arg1_id":"16958","arg2_id":"16959","normalized":[]},{"id":"16986","type":"CID","arg1_id":"16958","arg2_id":"16960","normalized":[]},{"id":"16987","type":"CID","arg1_id":"16958","arg2_id":"16963","normalized":[]},{"id":"16988","type":"CID","arg1_id":"16958","arg2_id":"16965","normalized":[]},{"id":"16989","type":"CID","arg1_id":"16958","arg2_id":"16967","normalized":[]},{"id":"16990","type":"CID","arg1_id":"16961","arg2_id":"16955","normalized":[]},{"id":"16991","type":"CID","arg1_id":"16961","arg2_id":"16957","normalized":[]},{"id":"16992","type":"CID","arg1_id":"16961","arg2_id":"16959","normalized":[]},{"id":"16993","type":"CID","arg1_id":"16961","arg2_id":"16960","normalized":[]},{"id":"16994","type":"CID","arg1_id":"16961","arg2_id":"16963","normalized":[]},{"id":"16995","type":"CID","arg1_id":"16961","arg2_id":"16965","normalized":[]},{"id":"16996","type":"CID","arg1_id":"16961","arg2_id":"16967","normalized":[]},{"id":"16997","type":"CID","arg1_id":"16962","arg2_id":"16955","normalized":[]},{"id":"16998","type":"CID","arg1_id":"16962","arg2_id":"16957","normalized":[]},{"id":"16999","type":"CID","arg1_id":"16962","arg2_id":"16959","normalized":[]},{"id":"17000","type":"CID","arg1_id":"16962","arg2_id":"16960","normalized":[]},{"id":"17001","type":"CID","arg1_id":"16962","arg2_id":"16963","normalized":[]},{"id":"17002","type":"CID","arg1_id":"16962","arg2_id":"16965","normalized":[]},{"id":"17003","type":"CID","arg1_id":"16962","arg2_id":"16967","normalized":[]},{"id":"17004","type":"CID","arg1_id":"16964","arg2_id":"16955","normalized":[]},{"id":"17005","type":"CID","arg1_id":"16964","arg2_id":"16957","normalized":[]},{"id":"17006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{"id":"17025","document_id":"8111719","passages":[{"id":"17026","type":"title","text":["Hallucinations and ifosfamide-induced neurotoxicity."],"offsets":[[0,52]]},{"id":"17027","type":"abstract","text":["BACKGROUND: Hallucinations as a symptom of central neurotoxicity are a known but poorly described side effect of ifosfamide. Most cases of ifosfamide-induced hallucinations have been reported with other mental status changes. METHODS: The authors interviewed six persons with ifosfamide-induced hallucinations in the presence of a clear sensorium. All patients were receiving high-dose ifosfamide as part of their bone marrow transplant procedure. RESULTS: Hallucinations occurred only when the patient's eyes were closed and, in all but one case, were reported as disturbing or frightening. Underreporting of these hallucinations by patients is likely. CONCLUSIONS: Hallucinations may be the sole or first manifestation of neurotoxicity. The incidence may be dose and infusion-time related. The clinician should be alerted for possible ifosfamide-induced hallucinations, which may occur without other signs of neurotoxicity. \"Eyes-closed\" hallucinatory experiences appear to be an unusual feature of this presentation. Patients anxious about this experience respond well to support and education about this occurrence. Optimal pharmacologic management of disturbed patients is unclear. If agitation becomes marked, high-potency neuroleptics (i.e., haloperidol) may be effective."],"offsets":[[53,1332]]}],"entities":[{"id":"17028","type":"Disease","text":["Hallucinations"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"17029","type":"Chemical","text":["ifosfamide"],"offsets":[[19,29]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"17030","type":"Disease","text":["neurotoxicity"],"offsets":[[38,51]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"17031","type":"Disease","text":["Hallucinations"],"offsets":[[65,79]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"17032","type":"Disease","text":["neurotoxicity"],"offsets":[[104,117]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"17033","type":"Chemical","text":["ifosfamide"],"offsets":[[166,176]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"17034","type":"Chemical","text":["ifosfamide"],"offsets":[[192,202]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"17035","type":"Disease","text":["hallucinations"],"offsets":[[211,225]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"17036","type":"Chemical","text":["ifosfamide"],"offsets":[[329,339]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"17037","type":"Disease","text":["hallucinations"],"offsets":[[348,362]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"17038","type":"Chemical","text":["ifosfamide"],"offsets":[[439,449]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"17039","type":"Disease","text":["Hallucinations"],"offsets":[[510,524]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"17040","type":"Disease","text":["hallucinations"],"offsets":[[669,683]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"17041","type":"Disease","text":["Hallucinations"],"offsets":[[720,734]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"17042","type":"Disease","text":["neurotoxicity"],"offsets":[[777,790]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"17043","type":"Chemical","text":["ifosfamide"],"offsets":[[890,900]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"17044","type":"Disease","text":["hallucinations"],"offsets":[[909,923]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"17045","type":"Disease","text":["neurotoxicity"],"offsets":[[964,977]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"17046","type":"Disease","text":["hallucinatory"],"offsets":[[993,1006]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"17047","type":"Disease","text":["agitation"],"offsets":[[1243,1252]],"normalized":[{"db_name":"MESH","db_id":"D011595"}]},{"id":"17048","type":"Chemical","text":["haloperidol"],"offsets":[[1302,1313]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]}],"events":[],"coreferences":[],"relations":[{"id":"17049","type":"CID","arg1_id":"17029","arg2_id":"17028","normalized":[]},{"id":"17050","type":"CID","arg1_id":"17029","arg2_id":"17031","normalized":[]},{"id":"17051","type":"CID","arg1_id":"17029","arg2_id":"17035","normalized":[]},{"id":"17052","type":"CID","arg1_id":"17029","arg2_id":"17037","normalized":[]},{"id":"17053","type":"CID","arg1_id":"17029","arg2_id":"17039","normalized":[]},{"id":"17054","type":"CID","arg1_id":"17029","arg2_id":"17040","normalized":[]},{"id":"17055","type":"CID","arg1_id":"17029","arg2_id":"17041","normalized":[]},{"id":"17056","type":"CID","arg1_id":"17029","arg2_id":"17044","normalized":[]},{"id":"17057","type":"CID","arg1_id":"17029","arg2_id":"17046","normalized":[]},{"id":"17058","type":"CID","arg1_id":"17033","arg2_id":"17028","normalized":[]},{"id":"17059","type":"CID","arg1_id":"17033","arg2_id":"17031","normalized":[]},{"id":"17060","type":"CID","arg1_id":"17033","arg2_id":"17035","normalized":[]},{"id":"17061","type":"CID","arg1_id":"17033","arg2_id":"17037","normalized":[]},{"id":"17062","type":"CID","arg1_id":"17033","arg2_id":"17039","normalized":[]},{"id":"17063","type":"CID","arg1_id":"17033","arg2_id":"17040","normalized":[]},{"id":"17064","type":"CID","arg1_id":"17033","arg2_id":"17041","normalized":[]},{"id":"17065","type":"CID","arg1_id":"17033","arg2_id":"17044","normalized":[]},{"id":"17066","type":"CID","arg1_id":"17033","arg2_id":"17046","normalized":[]},{"id":"17067","type":"CID","arg1_id":"17034","arg2_id":"17028","normalized":[]},{"id":"17068","type":"CID","arg1_id":"17034","arg2_id":"17031","normalized":[]},{"id":"17069","type":"CID","arg1_id":"17034","arg2_id":"17035","normalized":[]},{"id":"17070","type":"CID","arg1_id":"17034","arg2_id":"17037","normalized":[]},{"id":"17071","type":"CID","arg1_id":"17034","arg2_id":"17039","normalized":[]},{"id":"17072","type":"CID","arg1_id":"17034","arg2_id":"17040","normalized":[]},{"id":"17073","type":"CID","arg1_id":"17034","arg2_id":"17041","normalized":[]},{"id":"17074","type":"CID","arg1_id":"17034","arg2_id":"17044","normalized":[]},{"id":"17075","type":"CID","arg1_id":"17034","arg2_id":"17046","normalized":[]},{"id":"17076","type":"CID","arg1_id":"17036","arg2_id":"17028","normalized":[]},{"id":"17077","type":"CID","arg1_id":"17036","arg2_id":"17031","normalized":[]},{"id":"17078","type":"CID","arg1_id":"17036","arg2_id":"17035","normalized":[]},{"id":"17079","type":"CID","arg1_id":"17036","arg2_id":"17037","normalized":[]},{"id":"17080","type":"CID","arg1_id":"17036","arg2_id":"17039","normalized":[]},{"id":"17081","type":"CID","arg1_id":"17036","arg2_id":"17040","normalized":[]},{"id":"17082","type":"CID","arg1_id":"17036","arg2_id":"17041","normalized":[]},{"id":"17083","type":"CID","arg1_id":"17036","arg2_id":"17044","normalized":[]},{"id":"17084","type":"CID","arg1_id":"17036","arg2_id":"17046","normalized":[]},{"id":"17085","type":"CID","arg1_id":"17038","arg2_id":"17028","normalized":[]},{"id":"17086","type":"CID","arg1_id":"17038","arg2_id":"17031","normalized":[]},{"id":"17087","type":"CID","arg1_id":"17038","arg2_id":"17035","normalized":[]},{"id":"17088","type":"CID","arg1_id":"17038","arg2_id":"17037","normalized":[]},{"id":"17089","type":"CID","arg1_id":"17038","arg2_id":"17039","normalized":[]},{"id":"17090","type":"CID","arg1_id":"17038","arg2_id":"17040","normalized":[]},{"id":"17091","type":"CID","arg1_id":"17038","arg2_id":"17041","normalized":[]},{"id":"17092","type":"CID","arg1_id":"17038","arg2_id":"17044","normalized":[]},{"id":"17093","type":"CID","arg1_id":"17038","arg2_id":"17046","normalized":[]},{"id":"17094","type":"CID","arg1_id":"17043","arg2_id":"17028","normalized":[]},{"id":"17095","type":"CID","arg1_id":"17043","arg2_id":"17031","normalized":[]},{"id":"17096","type":"CID","arg1_id":"17043","arg2_id":"17035","normalized":[]},{"id":"17097","type":"CID","arg1_id":"17043","arg2_id":"17037","normalized":[]},{"id":"17098","type":"CID","arg1_id":"17043","arg2_id":"17039","normalized":[]},{"id":"17099","type":"CID","arg1_id":"17043","arg2_id":"17040","normalized":[]},{"id":"17100","type":"CID","arg1_id":"17043","arg2_id":"17041","normalized":[]},{"id":"17101","type":"CID","arg1_id":"17043","arg2_id":"17044","normalized":[]},{"id":"17102","type":"CID","arg1_id":"17043","arg2_id":"17046","normalized":[]}]}
{"id":"17103","document_id":"7059267","passages":[{"id":"17104","type":"title","text":["Chlorpropamide-induced optic neuropathy."],"offsets":[[0,40]]},{"id":"17105","type":"abstract","text":["A 65-year-old woman with adult-onset diabetes treated with chlorpropamide (Diabenese) had a toxic optic neuropathy that resolved with discontinuation of chlorpropamide therapy. Visual loss occurs in diabetics for a variety of reasons, and accurate diagnosis is necessary to institute appropriate therapy. The possibility of a drug-induced optic neuropathy should be considered in the differential diagnosis of visual loss in diabetics."],"offsets":[[41,476]]}],"entities":[{"id":"17106","type":"Chemical","text":["Chlorpropamide"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D002747"}]},{"id":"17107","type":"Disease","text":["optic neuropathy"],"offsets":[[23,39]],"normalized":[{"db_name":"MESH","db_id":"D009901"}]},{"id":"17108","type":"Disease","text":["adult-onset diabetes"],"offsets":[[66,86]],"normalized":[{"db_name":"MESH","db_id":"D003924"}]},{"id":"17109","type":"Chemical","text":["chlorpropamide"],"offsets":[[100,114]],"normalized":[{"db_name":"MESH","db_id":"D002747"}]},{"id":"17110","type":"Chemical","text":["Diabenese"],"offsets":[[116,125]],"normalized":[{"db_name":"MESH","db_id":"D002747"}]},{"id":"17111","type":"Disease","text":["toxic optic neuropathy"],"offsets":[[133,155]],"normalized":[{"db_name":"MESH","db_id":"D009901"}]},{"id":"17112","type":"Chemical","text":["chlorpropamide"],"offsets":[[194,208]],"normalized":[{"db_name":"MESH","db_id":"D002747"}]},{"id":"17113","type":"Disease","text":["Visual loss"],"offsets":[[218,229]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"17114","type":"Disease","text":["diabetics"],"offsets":[[240,249]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"17115","type":"Disease","text":["optic neuropathy"],"offsets":[[380,396]],"normalized":[{"db_name":"MESH","db_id":"D009901"}]},{"id":"17116","type":"Disease","text":["visual loss"],"offsets":[[451,462]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"17117","type":"Disease","text":["diabetics"],"offsets":[[466,475]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]}],"events":[],"coreferences":[],"relations":[{"id":"17118","type":"CID","arg1_id":"17106","arg2_id":"17107","normalized":[]},{"id":"17119","type":"CID","arg1_id":"17106","arg2_id":"17111","normalized":[]},{"id":"17120","type":"CID","arg1_id":"17106","arg2_id":"17115","normalized":[]},{"id":"17121","type":"CID","arg1_id":"17109","arg2_id":"17107","normalized":[]},{"id":"17122","type":"CID","arg1_id":"17109","arg2_id":"17111","normalized":[]},{"id":"17123","type":"CID","arg1_id":"17109","arg2_id":"17115","normalized":[]},{"id":"17124","type":"CID","arg1_id":"17110","arg2_id":"17107","normalized":[]},{"id":"17125","type":"CID","arg1_id":"17110","arg2_id":"17111","normalized":[]},{"id":"17126","type":"CID","arg1_id":"17110","arg2_id":"17115","normalized":[]},{"id":"17127","type":"CID","arg1_id":"17112","arg2_id":"17107","normalized":[]},{"id":"17128","type":"CID","arg1_id":"17112","arg2_id":"17111","normalized":[]},{"id":"17129","type":"CID","arg1_id":"17112","arg2_id":"17115","normalized":[]}]}
{"id":"17130","document_id":"6381653","passages":[{"id":"17131","type":"title","text":["Levodopa-induced dyskinesia and thalamotomy."],"offsets":[[0,44]]},{"id":"17132","type":"abstract","text":["Levodopa-induced dyskinesia of the limbs in thirteen cases of Parkinsonism, which was choreic, ballistic or dystonic in type, was alleviated almost completely by stereotaxic surgery using a microelectrode technique for the ventralis oralis anterior and posterior nuclei of the thalamus, but much less by the ventralis intermedius nucleus. Control of levodopa-induced dyskinesias by thalamic lesions in the course of routine treatment of Parkinsonism is discussed."],"offsets":[[45,508]]}],"entities":[{"id":"17133","type":"Chemical","text":["Levodopa"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"17134","type":"Disease","text":["dyskinesia"],"offsets":[[17,27]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"17135","type":"Chemical","text":["Levodopa"],"offsets":[[45,53]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"17136","type":"Disease","text":["dyskinesia"],"offsets":[[62,72]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"17137","type":"Disease","text":["Parkinsonism"],"offsets":[[107,119]],"normalized":[{"db_name":"MESH","db_id":"D010302"}]},{"id":"17138","type":"Disease","text":["dystonic"],"offsets":[[153,161]],"normalized":[{"db_name":"MESH","db_id":"D020821"}]},{"id":"17139","type":"Chemical","text":["levodopa"],"offsets":[[395,403]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"17140","type":"Disease","text":["dyskinesias"],"offsets":[[412,423]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"17141","type":"Disease","text":["thalamic lesions"],"offsets":[[427,443]],"normalized":[{"db_name":"MESH","db_id":"D013786"}]},{"id":"17142","type":"Disease","text":["Parkinsonism"],"offsets":[[482,494]],"normalized":[{"db_name":"MESH","db_id":"D010302"}]}],"events":[],"coreferences":[],"relations":[{"id":"17143","type":"CID","arg1_id":"17133","arg2_id":"17134","normalized":[]},{"id":"17144","type":"CID","arg1_id":"17133","arg2_id":"17136","normalized":[]},{"id":"17145","type":"CID","arg1_id":"17133","arg2_id":"17140","normalized":[]},{"id":"17146","type":"CID","arg1_id":"17135","arg2_id":"17134","normalized":[]},{"id":"17147","type":"CID","arg1_id":"17135","arg2_id":"17136","normalized":[]},{"id":"17148","type":"CID","arg1_id":"17135","arg2_id":"17140","normalized":[]},{"id":"17149","type":"CID","arg1_id":"17139","arg2_id":"17134","normalized":[]},{"id":"17150","type":"CID","arg1_id":"17139","arg2_id":"17136","normalized":[]},{"id":"17151","type":"CID","arg1_id":"17139","arg2_id":"17140","normalized":[]}]}
{"id":"17152","document_id":"3950060","passages":[{"id":"17153","type":"title","text":["Factors associated with nephrotoxicity and clinical outcome in patients receiving amikacin."],"offsets":[[0,91]]},{"id":"17154","type":"abstract","text":["Data from 60 patients treated with amikacin were analyzed for factors associated with nephrotoxicity. In 42 of these patients, data were examined for factors associated with clinical outcome. Variables evaluated included patient weight, age, sex, serum creatinine level, creatinine clearance, duration of therapy, total dose, mean daily dose, organism minimum inhibitory concentration (MIC), mean peak levels, mean trough levels, mean area under the serum concentration-time curve (AUC), total AUC, mean AUC greater than MIC, total AUC greater than MIC, mean Schumacher's intensity factor (IF), total IF, In (mean maximum concentration [Cmax]\/MIC). Model-dependent pharmacokinetic parameters were calculated by computer based on a one-compartment model. When the parameters were examined individually, duration of therapy and total AUC correlated significantly (P less than .05) with nephrotoxicity. In contrast, a stepwise discriminant function analysis identified only duration of therapy (P less than .001) as an important factor. Based on this model and on Bayes' theorem, the predictive accuracy of identifying \"nephrotoxic\" patients increased from 0.17 to 0.39. When examined individually, mean IF, MIC, total dose, mean daily dose, and ln (mean Cmax\/MIC) correlated significantly (P less than .05) with cure. In contrast, a simultaneous multivariable analysis identified IF, MIC, and total dose according to one model and ln (mean Cmax\/MIC) according to a second statistical model of parameters selected to have the greatest prospective value. Based on Bayes' theorem and the first model, the predictive accuracy of identifying patients not cured increased from 0.19 to 0.83. For the second model, the predictive accuracy increased from 0.19 to 0.50.(ABSTRACT TRUNCATED AT 250 WORDS)"],"offsets":[[92,1882]]}],"entities":[{"id":"17155","type":"Disease","text":["nephrotoxicity"],"offsets":[[24,38]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"17156","type":"Chemical","text":["amikacin"],"offsets":[[82,90]],"normalized":[{"db_name":"MESH","db_id":"D000583"}]},{"id":"17157","type":"Chemical","text":["amikacin"],"offsets":[[127,135]],"normalized":[{"db_name":"MESH","db_id":"D000583"}]},{"id":"17158","type":"Disease","text":["nephrotoxicity"],"offsets":[[178,192]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"17159","type":"Chemical","text":["creatinine"],"offsets":[[345,355]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"17160","type":"Chemical","text":["creatinine"],"offsets":[[363,373]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"17161","type":"Disease","text":["nephrotoxicity"],"offsets":[[976,990]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"17162","type":"Disease","text":["nephrotoxic"],"offsets":[[1209,1220]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"17163","type":"CID","arg1_id":"17156","arg2_id":"17155","normalized":[]},{"id":"17164","type":"CID","arg1_id":"17156","arg2_id":"17158","normalized":[]},{"id":"17165","type":"CID","arg1_id":"17156","arg2_id":"17161","normalized":[]},{"id":"17166","type":"CID","arg1_id":"17156","arg2_id":"17162","normalized":[]},{"id":"17167","type":"CID","arg1_id":"17157","arg2_id":"17155","normalized":[]},{"id":"17168","type":"CID","arg1_id":"17157","arg2_id":"17158","normalized":[]},{"id":"17169","type":"CID","arg1_id":"17157","arg2_id":"17161","normalized":[]},{"id":"17170","type":"CID","arg1_id":"17157","arg2_id":"17162","normalized":[]}]}
{"id":"17171","document_id":"3311455","passages":[{"id":"17172","type":"title","text":["Cardiac transplantation: improved quality of survival with a modified immunosuppressive protocol."],"offsets":[[0,97]]},{"id":"17173","type":"abstract","text":["The effects on renal function on two different immunosuppressive protocols were evaluated retrospectively in two subsequent groups of heart transplant recipients. In group I, cyclosporine was given before the procedure at a loading dose of 17.5 mg\/kg and then continued after the procedure to keep a whole blood level about 1000 ng\/ml. In group II, cyclosporine was started only after the procedure at a lower dosage and was complemented by azathioprine, which was used for the first postoperative week. Group II showed a better perioperative renal function as determined by serum blood urea nitrogen and serum creatinine levels. Group II also showed a significant decrease of chronic nephrotoxicity secondary to long-term therapy with cyclosporine. Despite this improvement in late renal function, group II still shows a slow rise in serum creatinine. We think that even these lower dosages of cyclosporine can cause chronic nephrotoxicity and that further modification of the immunosuppressive regimen is required to completely abolish this toxic side effect."],"offsets":[[98,1159]]}],"entities":[{"id":"17174","type":"Chemical","text":["cyclosporine"],"offsets":[[273,285]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"17175","type":"Chemical","text":["cyclosporine"],"offsets":[[447,459]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"17176","type":"Chemical","text":["azathioprine"],"offsets":[[539,551]],"normalized":[{"db_name":"MESH","db_id":"D001379"}]},{"id":"17177","type":"Chemical","text":["urea nitrogen"],"offsets":[[685,698]],"normalized":[{"db_name":"MESH","db_id":"D001806"}]},{"id":"17178","type":"Chemical","text":["creatinine"],"offsets":[[709,719]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"17179","type":"Disease","text":["nephrotoxicity"],"offsets":[[783,797]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"17180","type":"Chemical","text":["cyclosporine"],"offsets":[[834,846]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"17181","type":"Chemical","text":["creatinine"],"offsets":[[939,949]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"17182","type":"Chemical","text":["cyclosporine"],"offsets":[[993,1005]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"17183","type":"Disease","text":["nephrotoxicity"],"offsets":[[1024,1038]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"17184","type":"CID","arg1_id":"17174","arg2_id":"17179","normalized":[]},{"id":"17185","type":"CID","arg1_id":"17174","arg2_id":"17183","normalized":[]},{"id":"17186","type":"CID","arg1_id":"17175","arg2_id":"17179","normalized":[]},{"id":"17187","type":"CID","arg1_id":"17175","arg2_id":"17183","normalized":[]},{"id":"17188","type":"CID","arg1_id":"17180","arg2_id":"17179","normalized":[]},{"id":"17189","type":"CID","arg1_id":"17180","arg2_id":"17183","normalized":[]},{"id":"17190","type":"CID","arg1_id":"17182","arg2_id":"17179","normalized":[]},{"id":"17191","type":"CID","arg1_id":"17182","arg2_id":"17183","normalized":[]}]}
{"id":"17192","document_id":"2051906","passages":[{"id":"17193","type":"title","text":["Reversible cholestasis with bile duct injury following azathioprine therapy. A case report."],"offsets":[[0,91]]},{"id":"17194","type":"abstract","text":["A 67-year-old patient, with primary polymyositis and without previous evidence of liver disease, developed clinical and biochemical features of severe cholestasis 3 months after initiation of azathioprine therapy. Liver biopsy showed cholestasis with both cytological and architectural alterations of interlobular bile ducts. Azathioprine withdrawal resulted after 7 weeks in the resolution of clinical and biochemical abnormalities. It is believed that this is the first reported case of reversible azathioprine-induced cholestasis associated with histological evidence of bile duct injury."],"offsets":[[92,683]]}],"entities":[{"id":"17195","type":"Disease","text":["cholestasis"],"offsets":[[11,22]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"17196","type":"Disease","text":["bile duct injury"],"offsets":[[28,44]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"17197","type":"Chemical","text":["azathioprine"],"offsets":[[55,67]],"normalized":[{"db_name":"MESH","db_id":"D001379"}]},{"id":"17198","type":"Disease","text":["polymyositis"],"offsets":[[128,140]],"normalized":[{"db_name":"MESH","db_id":"D017285"}]},{"id":"17199","type":"Disease","text":["liver disease"],"offsets":[[174,187]],"normalized":[{"db_name":"MESH","db_id":"D008107"}]},{"id":"17200","type":"Disease","text":["cholestasis"],"offsets":[[243,254]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"17201","type":"Chemical","text":["azathioprine"],"offsets":[[284,296]],"normalized":[{"db_name":"MESH","db_id":"D001379"}]},{"id":"17202","type":"Disease","text":["cholestasis"],"offsets":[[326,337]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"17203","type":"Chemical","text":["Azathioprine"],"offsets":[[418,430]],"normalized":[{"db_name":"MESH","db_id":"D001379"}]},{"id":"17204","type":"Chemical","text":["azathioprine"],"offsets":[[592,604]],"normalized":[{"db_name":"MESH","db_id":"D001379"}]},{"id":"17205","type":"Disease","text":["cholestasis"],"offsets":[[613,624]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"17206","type":"Disease","text":["bile duct injury"],"offsets":[[666,682]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]}],"events":[],"coreferences":[],"relations":[{"id":"17207","type":"CID","arg1_id":"17197","arg2_id":"17195","normalized":[]},{"id":"17208","type":"CID","arg1_id":"17197","arg2_id":"17196","normalized":[]},{"id":"17209","type":"CID","arg1_id":"17197","arg2_id":"17200","normalized":[]},{"id":"17210","type":"CID","arg1_id":"17197","arg2_id":"17202","normalized":[]},{"id":"17211","type":"CID","arg1_id":"17197","arg2_id":"17205","normalized":[]},{"id":"17212","type":"CID","arg1_id":"17197","arg2_id":"17206","normalized":[]},{"id":"17213","type":"CID","arg1_id":"17201","arg2_id":"17195","normalized":[]},{"id":"17214","type":"CID","arg1_id":"17201","arg2_id":"17196","normalized":[]},{"id":"17215","type":"CID","arg1_id":"17201","arg2_id":"17200","normalized":[]},{"id":"17216","type":"CID","arg1_id":"17201","arg2_id":"17202","normalized":[]},{"id":"17217","type":"CID","arg1_id":"17201","arg2_id":"17205","normalized":[]},{"id":"17218","type":"CID","arg1_id":"17201","arg2_id":"17206","normalized":[]},{"id":"17219","type":"CID","arg1_id":"17203","arg2_id":"17195","normalized":[]},{"id":"17220","type":"CID","arg1_id":"17203","arg2_id":"17196","normalized":[]},{"id":"17221","type":"CID","arg1_id":"17203","arg2_id":"17200","normalized":[]},{"id":"17222","type":"CID","arg1_id":"17203","arg2_id":"17202","normalized":[]},{"id":"17223","type":"CID","arg1_id":"17203","arg2_id":"17205","normalized":[]},{"id":"17224","type":"CID","arg1_id":"17203","arg2_id":"17206","normalized":[]},{"id":"17225","type":"CID","arg1_id":"17204","arg2_id":"17195","normalized":[]},{"id":"17226","type":"CID","arg1_id":"17204","arg2_id":"17196","normalized":[]},{"id":"17227","type":"CID","arg1_id":"17204","arg2_id":"17200","normalized":[]},{"id":"17228","type":"CID","arg1_id":"17204","arg2_id":"17202","normalized":[]},{"id":"17229","type":"CID","arg1_id":"17204","arg2_id":"17205","normalized":[]},{"id":"17230","type":"CID","arg1_id":"17204","arg2_id":"17206","normalized":[]}]}
{"id":"17231","document_id":"2021202","passages":[{"id":"17232","type":"title","text":["Renal function and hemodynamics during prolonged isoflurane-induced hypotension in humans."],"offsets":[[0,90]]},{"id":"17233","type":"abstract","text":["The effect of isoflurane-induced hypotension on glomerular function and renal blood flow was investigated in 20 human subjects. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and para-aminohippurate (PAH) clearance, respectively. Anesthesia was maintained with fentanyl, nitrous oxide, oxygen, and isoflurane. Hypotension was induced for 236.9 +\/- 15.1 min by increasing the isoflurane inspired concentration to maintain a mean arterial pressure of 59.8 +\/- 0.4 mmHg. GFR and ERPF decreased with the induction of anesthesia but not significantly more during hypotension. Postoperatively, ERPF returned to preoperative values, whereas GFR was higher than preoperative values. Renal vascular resistance increased during anesthesia but decreased when hypotension was induced, allowing the maintenance of renal blood flow. We conclude that renal compensatory mechanisms are preserved during isoflurane-induced hypotension and that renal function and hemodynamics quickly return to normal when normotension is resumed."],"offsets":[[91,1153]]}],"entities":[{"id":"17234","type":"Chemical","text":["isoflurane"],"offsets":[[49,59]],"normalized":[{"db_name":"MESH","db_id":"D007530"}]},{"id":"17235","type":"Disease","text":["hypotension"],"offsets":[[68,79]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"17236","type":"Chemical","text":["isoflurane"],"offsets":[[105,115]],"normalized":[{"db_name":"MESH","db_id":"D007530"}]},{"id":"17237","type":"Disease","text":["hypotension"],"offsets":[[124,135]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"17238","type":"Chemical","text":["para-aminohippurate"],"offsets":[[319,338]],"normalized":[{"db_name":"MESH","db_id":"D010130"}]},{"id":"17239","type":"Chemical","text":["PAH"],"offsets":[[340,343]],"normalized":[{"db_name":"MESH","db_id":"D010130"}]},{"id":"17240","type":"Chemical","text":["fentanyl"],"offsets":[[401,409]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"17241","type":"Chemical","text":["nitrous oxide"],"offsets":[[411,424]],"normalized":[{"db_name":"MESH","db_id":"D009609"}]},{"id":"17242","type":"Chemical","text":["oxygen"],"offsets":[[426,432]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"17243","type":"Chemical","text":["isoflurane"],"offsets":[[438,448]],"normalized":[{"db_name":"MESH","db_id":"D007530"}]},{"id":"17244","type":"Disease","text":["Hypotension"],"offsets":[[450,461]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"17245","type":"Chemical","text":["isoflurane"],"offsets":[[515,525]],"normalized":[{"db_name":"MESH","db_id":"D007530"}]},{"id":"17246","type":"Disease","text":["hypotension"],"offsets":[[698,709]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"17247","type":"Disease","text":["hypotension"],"offsets":[[888,899]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"17248","type":"Chemical","text":["isoflurane"],"offsets":[[1027,1037]],"normalized":[{"db_name":"MESH","db_id":"D007530"}]},{"id":"17249","type":"Disease","text":["hypotension"],"offsets":[[1046,1057]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]}],"events":[],"coreferences":[],"relations":[{"id":"17250","type":"CID","arg1_id":"17234","arg2_id":"17235","normalized":[]},{"id":"17251","type":"CID","arg1_id":"17234","arg2_id":"17237","normalized":[]},{"id":"17252","type":"CID","arg1_id":"17234","arg2_id":"17244","normalized":[]},{"id":"17253","type":"CID","arg1_id":"17234","arg2_id":"17246","normalized":[]},{"id":"17254","type":"CID","arg1_id":"17234","arg2_id":"17247","normalized":[]},{"id":"17255","type":"CID","arg1_id":"17234","arg2_id":"17249","normalized":[]},{"id":"17256","type":"CID","arg1_id":"17236","arg2_id":"17235","normalized":[]},{"id":"17257","type":"CID","arg1_id":"17236","arg2_id":"17237","normalized":[]},{"id":"17258","type":"CID","arg1_id":"17236","arg2_id":"17244","normalized":[]},{"id":"17259","type":"CID","arg1_id":"17236","arg2_id":"17246","normalized":[]},{"id":"17260","type":"CID","arg1_id":"17236","arg2_id":"17247","normalized":[]},{"id":"17261","type":"CID","arg1_id":"17236","arg2_id":"17249","normalized":[]},{"id":"17262","type":"CID","arg1_id":"17243","arg2_id":"17235","normalized":[]},{"id":"17263","type":"CID","arg1_id":"17243","arg2_id":"17237","normalized":[]},{"id":"17264","type":"CID","arg1_id":"17243","arg2_id":"17244","normalized":[]},{"id":"17265","type":"CID","arg1_id":"17243","arg2_id":"17246","normalized":[]},{"id":"17266","type":"CID","arg1_id":"17243","arg2_id":"17247","normalized":[]},{"id":"17267","type":"CID","arg1_id":"17243","arg2_id":"17249","normalized":[]},{"id":"17268","type":"CID","arg1_id":"17245","arg2_id":"17235","normalized":[]},{"id":"17269","type":"CID","arg1_id":"17245","arg2_id":"17237","normalized":[]},{"id":"17270","type":"CID","arg1_id":"17245","arg2_id":"17244","normalized":[]},{"id":"17271","type":"CID","arg1_id":"17245","arg2_id":"17246","normalized":[]},{"id":"17272","type":"CID","arg1_id":"17245","arg2_id":"17247","normalized":[]},{"id":"17273","type":"CID","arg1_id":"17245","arg2_id":"17249","normalized":[]},{"id":"17274","type":"CID","arg1_id":"17248","arg2_id":"17235","normalized":[]},{"id":"17275","type":"CID","arg1_id":"17248","arg2_id":"17237","normalized":[]},{"id":"17276","type":"CID","arg1_id":"17248","arg2_id":"17244","normalized":[]},{"id":"17277","type":"CID","arg1_id":"17248","arg2_id":"17246","normalized":[]},{"id":"17278","type":"CID","arg1_id":"17248","arg2_id":"17247","normalized":[]},{"id":"17279","type":"CID","arg1_id":"17248","arg2_id":"17249","normalized":[]}]}
{"id":"17280","document_id":"1848636","passages":[{"id":"17281","type":"title","text":["Debrisoquine phenotype and the pharmacokinetics and beta-2 receptor pharmacodynamics of metoprolol and its enantiomers."],"offsets":[[0,119]]},{"id":"17282","type":"abstract","text":["The metabolism of the cardioselective beta-blocker metoprolol is under genetic control of the debrisoquine\/sparteine type. The two metabolic phenotypes, extensive (EM) and poor metabolizers (PM), show different stereoselective metabolism, resulting in apparently higher beta-1 adrenoceptor antagonistic potency of racemic metoprolol in EMs. We investigated if the latter also applies to the beta-2 adrenoceptor antagonism by metoprolol. The drug effect studied was the antagonism by metoprolol of terbutaline-induced hypokalemia. By using pharmacokinetic pharmacodynamic modeling the pharmacodynamics of racemic metoprolol and the active S-isomer, were quantitated in EMs and PMs in terms of IC50 values, representing metoprolol plasma concentrations resulting in half-maximum receptor occupancy. Six EMs received 0.5 mg of terbutaline s.c. on two different occasions: 1) 1 hr after administration of a placebo and 2) 1 hr after 150 mg of metoprolol p.o. Five PMs were studied according to the same protocol, except for a higher terbutaline dose (0.75 mg) on day 2. Blood samples for the analysis of plasma potassium, terbutaline, metoprolol (racemic, R- and S-isomer), and alpha-hydroxymetoprolol concentrations were taken at regular time intervals, during 8 hr after metoprolol. In PMs, metoprolol increased the terbutaline area under the plasma concentration vs. time curve (+67%). Higher metoprolol\/alpha-hydroxymetoprolol ratios in PMs were predictive for higher R-\/S-isomer ratios of unchanged drug. There was a difference in metoprolol potency with higher racemic metoprolol IC50 values in PMs (72 +\/- 7 ng.ml-1) than EMs (42 +\/- 8 ng.ml-1, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)"],"offsets":[[120,1819]]}],"entities":[{"id":"17283","type":"Chemical","text":["Debrisoquine"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D003647"}]},{"id":"17284","type":"Chemical","text":["metoprolol"],"offsets":[[88,98]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"17285","type":"Chemical","text":["metoprolol"],"offsets":[[171,181]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"17286","type":"Chemical","text":["debrisoquine"],"offsets":[[214,226]],"normalized":[{"db_name":"MESH","db_id":"D003647"}]},{"id":"17287","type":"Chemical","text":["sparteine"],"offsets":[[227,236]],"normalized":[{"db_name":"MESH","db_id":"D013034"}]},{"id":"17288","type":"Chemical","text":["metoprolol"],"offsets":[[442,452]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"17289","type":"Chemical","text":["metoprolol"],"offsets":[[545,555]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"17290","type":"Chemical","text":["metoprolol"],"offsets":[[603,613]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"17291","type":"Chemical","text":["terbutaline"],"offsets":[[617,628]],"normalized":[{"db_name":"MESH","db_id":"D013726"}]},{"id":"17292","type":"Disease","text":["hypokalemia"],"offsets":[[637,648]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"17293","type":"Chemical","text":["metoprolol"],"offsets":[[732,742]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"17294","type":"Chemical","text":["metoprolol"],"offsets":[[838,848]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"17295","type":"Chemical","text":["terbutaline"],"offsets":[[944,955]],"normalized":[{"db_name":"MESH","db_id":"D013726"}]},{"id":"17296","type":"Chemical","text":["metoprolol"],"offsets":[[1059,1069]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"17297","type":"Chemical","text":["terbutaline"],"offsets":[[1149,1160]],"normalized":[{"db_name":"MESH","db_id":"D013726"}]},{"id":"17298","type":"Chemical","text":["potassium"],"offsets":[[1227,1236]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"17299","type":"Chemical","text":["terbutaline"],"offsets":[[1238,1249]],"normalized":[{"db_name":"MESH","db_id":"D013726"}]},{"id":"17300","type":"Chemical","text":["metoprolol"],"offsets":[[1251,1261]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"17301","type":"Chemical","text":["alpha-hydroxymetoprolol"],"offsets":[[1294,1317]],"normalized":[{"db_name":"MESH","db_id":"C029504"}]},{"id":"17302","type":"Chemical","text":["metoprolol"],"offsets":[[1389,1399]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"17303","type":"Chemical","text":["metoprolol"],"offsets":[[1409,1419]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"17304","type":"Chemical","text":["terbutaline"],"offsets":[[1434,1445]],"normalized":[{"db_name":"MESH","db_id":"D013726"}]},{"id":"17305","type":"Chemical","text":["metoprolol"],"offsets":[[1512,1522]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"17306","type":"Chemical","text":["alpha-hydroxymetoprolol"],"offsets":[[1523,1546]],"normalized":[{"db_name":"MESH","db_id":"C029504"}]},{"id":"17307","type":"Chemical","text":["metoprolol"],"offsets":[[1652,1662]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"17308","type":"Chemical","text":["metoprolol"],"offsets":[[1691,1701]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]}],"events":[],"coreferences":[],"relations":[{"id":"17309","type":"CID","arg1_id":"17291","arg2_id":"17292","normalized":[]},{"id":"17310","type":"CID","arg1_id":"17295","arg2_id":"17292","normalized":[]},{"id":"17311","type":"CID","arg1_id":"17297","arg2_id":"17292","normalized":[]},{"id":"17312","type":"CID","arg1_id":"17299","arg2_id":"17292","normalized":[]},{"id":"17313","type":"CID","arg1_id":"17304","arg2_id":"17292","normalized":[]}]}
{"id":"17314","document_id":"1445986","passages":[{"id":"17315","type":"title","text":["Cefotetan-induced immune hemolytic anemia."],"offsets":[[0,42]]},{"id":"17316","type":"abstract","text":["Immune hemolytic anemia due to a drug-adsorption mechanism has been described primarily in patients receiving penicillins and first-generation cephalosporins. We describe a patient who developed anemia while receiving intravenous cefotetan. Cefotetan-dependent antibodies were detected in the patient's serum and in an eluate prepared from his red blood cells. The eluate also reacted weakly with red blood cells in the absence of cefotetan, suggesting the concomitant formation of warm-reactive autoantibodies. These observations, in conjunction with clinical and laboratory evidence of extravascular hemolysis, are consistent with drug-induced hemolytic anemia, possibly involving both drug-adsorption and autoantibody formation mechanisms. This case emphasizes the need for increased awareness of hemolytic reactions to all cephalosporins."],"offsets":[[43,885]]}],"entities":[{"id":"17317","type":"Chemical","text":["Cefotetan"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D015313"}]},{"id":"17318","type":"Disease","text":["hemolytic anemia"],"offsets":[[25,41]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"17319","type":"Disease","text":["hemolytic anemia"],"offsets":[[50,66]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"17320","type":"Chemical","text":["penicillins"],"offsets":[[153,164]],"normalized":[{"db_name":"MESH","db_id":"D010406"}]},{"id":"17321","type":"Chemical","text":["cephalosporins"],"offsets":[[186,200]],"normalized":[{"db_name":"MESH","db_id":"D002511"}]},{"id":"17322","type":"Disease","text":["anemia"],"offsets":[[238,244]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"17323","type":"Chemical","text":["cefotetan"],"offsets":[[273,282]],"normalized":[{"db_name":"MESH","db_id":"D015313"}]},{"id":"17324","type":"Chemical","text":["Cefotetan"],"offsets":[[284,293]],"normalized":[{"db_name":"MESH","db_id":"D015313"}]},{"id":"17325","type":"Chemical","text":["cefotetan"],"offsets":[[474,483]],"normalized":[{"db_name":"MESH","db_id":"D015313"}]},{"id":"17326","type":"Disease","text":["hemolysis"],"offsets":[[645,654]],"normalized":[{"db_name":"MESH","db_id":"D006461"}]},{"id":"17327","type":"Disease","text":["hemolytic anemia"],"offsets":[[689,705]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"17328","type":"Chemical","text":["cephalosporins"],"offsets":[[870,884]],"normalized":[{"db_name":"MESH","db_id":"D002511"}]}],"events":[],"coreferences":[],"relations":[{"id":"17329","type":"CID","arg1_id":"17317","arg2_id":"17318","normalized":[]},{"id":"17330","type":"CID","arg1_id":"17317","arg2_id":"17319","normalized":[]},{"id":"17331","type":"CID","arg1_id":"17317","arg2_id":"17327","normalized":[]},{"id":"17332","type":"CID","arg1_id":"17323","arg2_id":"17318","normalized":[]},{"id":"17333","type":"CID","arg1_id":"17323","arg2_id":"17319","normalized":[]},{"id":"17334","type":"CID","arg1_id":"17323","arg2_id":"17327","normalized":[]},{"id":"17335","type":"CID","arg1_id":"17324","arg2_id":"17318","normalized":[]},{"id":"17336","type":"CID","arg1_id":"17324","arg2_id":"17319","normalized":[]},{"id":"17337","type":"CID","arg1_id":"17324","arg2_id":"17327","normalized":[]},{"id":"17338","type":"CID","arg1_id":"17325","arg2_id":"17318","normalized":[]},{"id":"17339","type":"CID","arg1_id":"17325","arg2_id":"17319","normalized":[]},{"id":"17340","type":"CID","arg1_id":"17325","arg2_id":"17327","normalized":[]}]}
{"id":"17341","document_id":"982002","passages":[{"id":"17342","type":"title","text":["Acute renal failure subsequent to the administration of rifampicin. A follow-up study of cases reported earlier."],"offsets":[[0,112]]},{"id":"17343","type":"abstract","text":["A clinical presentation is made of a 2-3 year follow-up of six cases of acute renal failure that have been reported earlier. The patients had developed transient renal failure after the intermittent administration of rifampicin. The stage of olig-anuria lasted for 1-3 weeks, and five of the patients were treated by hemodialysis. Two of the patients died due to unrelated causes during the follow-up period. The four patients re-examined were clinically cured. Pathologic findings by light microscopy and immunofluorescence at biopsy were scarce. Nothing abnormal was seen by electron microscopy in two of the cases studied. Renal function was normal. In three cases the excretion at 131I-hippuran renography was slightly slowed. Although in the acute stage the renal lesions histologically appeared toxic, evidence suggestive of an immunological mechanism cannot be excluded."],"offsets":[[113,990]]}],"entities":[{"id":"17344","type":"Disease","text":["Acute renal failure"],"offsets":[[0,19]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"17345","type":"Chemical","text":["rifampicin"],"offsets":[[56,66]],"normalized":[{"db_name":"MESH","db_id":"D012293"}]},{"id":"17346","type":"Disease","text":["acute renal failure"],"offsets":[[185,204]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"17347","type":"Disease","text":["renal failure"],"offsets":[[275,288]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"17348","type":"Chemical","text":["rifampicin"],"offsets":[[330,340]],"normalized":[{"db_name":"MESH","db_id":"D012293"}]},{"id":"17349","type":"Disease","text":["anuria"],"offsets":[[360,366]],"normalized":[{"db_name":"MESH","db_id":"D001002"}]},{"id":"17350","type":"Disease","text":["renal lesions"],"offsets":[[876,889]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"17351","type":"CID","arg1_id":"17345","arg2_id":"17344","normalized":[]},{"id":"17352","type":"CID","arg1_id":"17345","arg2_id":"17346","normalized":[]},{"id":"17353","type":"CID","arg1_id":"17348","arg2_id":"17344","normalized":[]},{"id":"17354","type":"CID","arg1_id":"17348","arg2_id":"17346","normalized":[]}]}
{"id":"17355","document_id":"343678","passages":[{"id":"17356","type":"title","text":["Type B hepatitis after needle-stick exposure: prevention with hepatitis B immune globulin. Final report of the Veterans Administration Cooperative Study."],"offsets":[[0,153]]},{"id":"17357","type":"abstract","text":["Hepatitis B immune globulin (HBIG) and immune serum globulin (ISG) were examined in a randomized, double-blind trial to assess their relative efficacies in preventing type B hepatitis after needle-stick exposure to hepatitis B surface antigen (HBsAG)-positive donors. Clinical hepatitis developed in 1.4% of HBIG and in 5.9% of ISG recipients (P = 0.016), and seroconversion (anti-HBs) occurred in 5.6% and 20.7% of them respectively (P less than 0.001). Mild and transient side-effects were noted in 3.0% of ISG and in 3.2% of HBIG recipients. Available donor sera were examined for DNA polymerase (DNAP) and e antigen and antibody (HBeAg; anti-HBE). Both DNAP and HBeAg showed a highly statistically significant correlation with the infectivity of HBsAg-positive donors. Hepatitis B immune globulin remained significantly superior to ISG in preventing type B hepatitis even when the analysis was confined to these two high-risk subgroups. The efficacy of ISG in preventing type B hepatitis cannot be ascertained because a true placebo group was not included."],"offsets":[[154,1214]]}],"entities":[{"id":"17358","type":"Disease","text":["Type B hepatitis"],"offsets":[[0,16]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"17359","type":"Disease","text":["hepatitis B"],"offsets":[[62,73]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"17360","type":"Disease","text":["Hepatitis B"],"offsets":[[154,165]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"17361","type":"Disease","text":["type B hepatitis"],"offsets":[[321,337]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"17362","type":"Chemical","text":["hepatitis B surface antigen"],"offsets":[[369,396]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"17363","type":"Chemical","text":["HBsAG"],"offsets":[[398,403]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"17364","type":"Disease","text":["hepatitis"],"offsets":[[431,440]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"17365","type":"Chemical","text":["HBeAg"],"offsets":[[788,793]],"normalized":[{"db_name":"MESH","db_id":"D006513"}]},{"id":"17366","type":"Chemical","text":["HBeAg"],"offsets":[[820,825]],"normalized":[{"db_name":"MESH","db_id":"D006513"}]},{"id":"17367","type":"Chemical","text":["HBsAg"],"offsets":[[904,909]],"normalized":[{"db_name":"MESH","db_id":"D006514"}]},{"id":"17368","type":"Disease","text":["Hepatitis B"],"offsets":[[927,938]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"17369","type":"Disease","text":["type B hepatitis"],"offsets":[[1008,1024]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]},{"id":"17370","type":"Disease","text":["type B hepatitis"],"offsets":[[1129,1145]],"normalized":[{"db_name":"MESH","db_id":"D006509"}]}],"events":[],"coreferences":[],"relations":[{"id":"17371","type":"CID","arg1_id":"17365","arg2_id":"17358","normalized":[]},{"id":"17372","type":"CID","arg1_id":"17365","arg2_id":"17359","normalized":[]},{"id":"17373","type":"CID","arg1_id":"17365","arg2_id":"17360","normalized":[]},{"id":"17374","type":"CID","arg1_id":"17365","arg2_id":"17361","normalized":[]},{"id":"17375","type":"CID","arg1_id":"17365","arg2_id":"17368","normalized":[]},{"id":"17376","type":"CID","arg1_id":"17365","arg2_id":"17369","normalized":[]},{"id":"17377","type":"CID","arg1_id":"17365","arg2_id":"17370","normalized":[]},{"id":"17378","type":"CID","arg1_id":"17366","arg2_id":"17358","normalized":[]},{"id":"17379","type":"CID","arg1_id":"17366","arg2_id":"17359","normalized":[]},{"id":"17380","type":"CID","arg1_id":"17366","arg2_id":"17360","normalized":[]},{"id":"17381","type":"CID","arg1_id":"17366","arg2_id":"17361","normalized":[]},{"id":"17382","type":"CID","arg1_id":"17366","arg2_id":"17368","normalized":[]},{"id":"17383","type":"CID","arg1_id":"17366","arg2_id":"17369","normalized":[]},{"id":"17384","type":"CID","arg1_id":"17366","arg2_id":"17370","normalized":[]}]}
{"id":"17385","document_id":"8888541","passages":[{"id":"17386","type":"title","text":["Serotonin syndrome from venlafaxine-tranylcypromine interaction."],"offsets":[[0,64]]},{"id":"17387","type":"abstract","text":["Excessive stimulation of serotonin 5HT1A receptors causes a syndrome of serotonin excess that consists of shivering, muscle rigidity, salivation, confusion, agitation and hyperthermia. The most common cause of this syndrome is an interaction between a monoamine oxidase inhibitor (MAOI) and a specific serotonin reuptake inhibitor. Venlafaxine is a new antidepressant agent that inhibits the reuptake of serotonin and norepinephrine. We report a venlafaxine-MAOI interaction that resulted in the serotonin syndrome in a 23-y-old male who was taking tranylcypromine for depression. He had been well until the morning of presentation when he took 1\/2 tab of venlafaxine. Within 2 h he became confused with jerking movements of his extremities, tremors and rigidity. He was brought directly to a hospital where he was found to be agitated and confused with shivering, myoclonic jerks, rigidity, salivation and diaphoresis. His pupils were 7 mm and sluggishly reactive to light. Vital signs were: blood pressure 120\/67 mm Hg, heart rate 127\/min, respiratory rate 28\/min, and temperature 97 F. After 180 mg of diazepam i.v. he remained tremulous with muscle rigidity and clenched jaws. He was intubated for airway protection and because of hypoventilation, and was paralyzed to control muscle rigidity. His subsequent course was remarkable for non-immune thrombocytopenia which resolved. The patient's maximal temperature was 101.2 F and his CPK remained < 500 units\/L with no other evidence of rhabdomyolysis. His mental status normalized and he was transferred to a psychiatry ward. This patient survived without sequelae due to the aggressive sedation and neuromuscular paralysis."],"offsets":[[65,1743]]}],"entities":[{"id":"17388","type":"Disease","text":["Serotonin syndrome"],"offsets":[[0,18]],"normalized":[{"db_name":"MESH","db_id":"D020230"}]},{"id":"17389","type":"Chemical","text":["venlafaxine"],"offsets":[[24,35]],"normalized":[{"db_name":"MESH","db_id":"C047426"}]},{"id":"17390","type":"Chemical","text":["tranylcypromine"],"offsets":[[36,51]],"normalized":[{"db_name":"MESH","db_id":"D014191"}]},{"id":"17391","type":"Chemical","text":["serotonin"],"offsets":[[90,99]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"17392","type":"Chemical","text":["serotonin"],"offsets":[[137,146]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"17393","type":"Disease","text":["muscle rigidity"],"offsets":[[182,197]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"17394","type":"Disease","text":["salivation"],"offsets":[[199,209]],"normalized":[{"db_name":"MESH","db_id":"D012798"}]},{"id":"17395","type":"Disease","text":["confusion"],"offsets":[[211,220]],"normalized":[{"db_name":"MESH","db_id":"D003221"}]},{"id":"17396","type":"Disease","text":["agitation"],"offsets":[[222,231]],"normalized":[{"db_name":"MESH","db_id":"D011595"}]},{"id":"17397","type":"Disease","text":["hyperthermia"],"offsets":[[236,248]],"normalized":[{"db_name":"MESH","db_id":"D005334"}]},{"id":"17398","type":"Chemical","text":["serotonin"],"offsets":[[367,376]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"17399","type":"Chemical","text":["Venlafaxine"],"offsets":[[397,408]],"normalized":[{"db_name":"MESH","db_id":"C047426"}]},{"id":"17400","type":"Chemical","text":["serotonin"],"offsets":[[469,478]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"17401","type":"Chemical","text":["norepinephrine"],"offsets":[[483,497]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"17402","type":"Chemical","text":["venlafaxine"],"offsets":[[511,522]],"normalized":[{"db_name":"MESH","db_id":"C047426"}]},{"id":"17403","type":"Disease","text":["serotonin syndrome"],"offsets":[[561,579]],"normalized":[{"db_name":"MESH","db_id":"D020230"}]},{"id":"17404","type":"Chemical","text":["tranylcypromine"],"offsets":[[614,629]],"normalized":[{"db_name":"MESH","db_id":"D014191"}]},{"id":"17405","type":"Disease","text":["depression"],"offsets":[[634,644]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"17406","type":"Chemical","text":["venlafaxine"],"offsets":[[721,732]],"normalized":[{"db_name":"MESH","db_id":"C047426"}]},{"id":"17407","type":"Disease","text":["tremors"],"offsets":[[807,814]],"normalized":[{"db_name":"MESH","db_id":"D014202"}]},{"id":"17408","type":"Disease","text":["rigidity"],"offsets":[[819,827]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"17409","type":"Disease","text":["myoclonic jerks"],"offsets":[[930,945]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"17410","type":"Disease","text":["rigidity"],"offsets":[[947,955]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"17411","type":"Disease","text":["salivation"],"offsets":[[957,967]],"normalized":[{"db_name":"MESH","db_id":"D012798"}]},{"id":"17412","type":"Chemical","text":["diazepam"],"offsets":[[1170,1178]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"17413","type":"Disease","text":["muscle rigidity"],"offsets":[[1211,1226]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"17414","type":"Disease","text":["hypoventilation"],"offsets":[[1300,1315]],"normalized":[{"db_name":"MESH","db_id":"D007040"}]},{"id":"17415","type":"Disease","text":["paralyzed"],"offsets":[[1325,1334]],"normalized":[{"db_name":"MESH","db_id":"D010243"}]},{"id":"17416","type":"Disease","text":["muscle 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{"id":"17504","document_id":"8106150","passages":[{"id":"17505","type":"title","text":["Effect of nondopaminergic drugs on L-dopa-induced dyskinesias in MPTP-treated monkeys."],"offsets":[[0,86]]},{"id":"17506","type":"abstract","text":["A group of four monkeys was rendered parkinsonian with the toxin MPTP. They were then treated chronically with L-DOPA\/benserazide 50\/12.5 mg\/kg given orally daily for 2 months. This dose produced a striking antiparkinsonian effect, but all animals manifested dyskinesia. A series of agents acting primarily on neurotransmitters other than dopamine were then tested in combination with L-DOPA to see if the dyskinetic movements would be modified. Several drugs, including clonidine, physostigmine, methysergide, 5-MDOT, propranolol, and MK-801, markedly reduced the dyskinetic movements but at the cost of a return of parkinsonian symptomatology. However, yohimbine and meperidine reduced predominantly the dyskinetic movements. Baclofen was also useful in one monkey against a more dystonic form of dyskinesia. Atropine converted the dystonic movements into chorea."],"offsets":[[87,952]]}],"entities":[{"id":"17507","type":"Chemical","text":["L-dopa"],"offsets":[[35,41]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"17508","type":"Disease","text":["dyskinesias"],"offsets":[[50,61]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"17509","type":"Chemical","text":["MPTP"],"offsets":[[65,69]],"normalized":[{"db_name":"MESH","db_id":"D015632"}]},{"id":"17510","type":"Disease","text":["parkinsonian"],"offsets":[[124,136]],"normalized":[{"db_name":"MESH","db_id":"D020734"}]},{"id":"17511","type":"Chemical","text":["MPTP"],"offsets":[[152,156]],"normalized":[{"db_name":"MESH","db_id":"D015632"}]},{"id":"17512","type":"Chemical","text":["L-DOPA\/benserazide"],"offsets":[[198,216]],"normalized":[{"db_name":"MESH","db_id":"C005177"}]},{"id":"17513","type":"Disease","text":["dyskinesia"],"offsets":[[346,356]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"17514","type":"Chemical","text":["dopamine"],"offsets":[[426,434]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"17515","type":"Chemical","text":["L-DOPA"],"offsets":[[472,478]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"17516","type":"Disease","text":["dyskinetic"],"offsets":[[493,503]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"17517","type":"Chemical","text":["clonidine"],"offsets":[[558,567]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"17518","type":"Chemical","text":["physostigmine"],"offsets":[[569,582]],"normalized":[{"db_name":"MESH","db_id":"D010830"}]},{"id":"17519","type":"Chemical","text":["methysergide"],"offsets":[[584,596]],"normalized":[{"db_name":"MESH","db_id":"D008784"}]},{"id":"17520","type":"Chemical","text":["5-MDOT"],"offsets":[[598,604]],"normalized":[]},{"id":"17521","type":"Chemical","text":["propranolol"],"offsets":[[606,617]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"17522","type":"Chemical","text":["MK-801"],"offsets":[[623,629]],"normalized":[{"db_name":"MESH","db_id":"D016291"}]},{"id":"17523","type":"Disease","text":["dyskinetic"],"offsets":[[652,662]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"17524","type":"Disease","text":["parkinsonian"],"offsets":[[704,716]],"normalized":[{"db_name":"MESH","db_id":"D020734"}]},{"id":"17525","type":"Chemical","text":["yohimbine"],"offsets":[[742,751]],"normalized":[{"db_name":"MESH","db_id":"D015016"}]},{"id":"17526","type":"Chemical","text":["meperidine"],"offsets":[[756,766]],"normalized":[{"db_name":"MESH","db_id":"D008614"}]},{"id":"17527","type":"Disease","text":["dyskinetic"],"offsets":[[793,803]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"17528","type":"Chemical","text":["Baclofen"],"offsets":[[815,823]],"normalized":[{"db_name":"MESH","db_id":"D001418"}]},{"id":"17529","type":"Disease","text":["dystonic"],"offsets":[[869,877]],"normalized":[{"db_name":"MESH","db_id":"D020821"}]},{"id":"17530","type":"Disease","text":["dyskinesia"],"offsets":[[886,896]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"17531","type":"Chemical","text":["Atropine"],"offsets":[[898,906]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"17532","type":"Disease","text":["dystonic"],"offsets":[[921,929]],"normalized":[{"db_name":"MESH","db_id":"D020821"}]},{"id":"17533","type":"Disease","text":["chorea"],"offsets":[[945,951]],"normalized":[{"db_name":"MESH","db_id":"D002819"}]}],"events":[],"coreferences":[],"relations":[{"id":"17534","type":"CID","arg1_id":"17512","arg2_id":"17508","normalized":[]},{"id":"17535","type":"CID","arg1_id":"17512","arg2_id":"17513","normalized":[]},{"id":"17536","type":"CID","arg1_id":"17512","arg2_id":"17516","normalized":[]},{"id":"17537","type":"CID","arg1_id":"17512","arg2_id":"17523","normalized":[]},{"id":"17538","type":"CID","arg1_id":"17512","arg2_id":"17527","normalized":[]},{"id":"17539","type":"CID","arg1_id":"17512","arg2_id":"17530","normalized":[]},{"id":"17540","type":"CID","arg1_id":"17509","arg2_id":"17510","normalized":[]},{"id":"17541","type":"CID","arg1_id":"17509","arg2_id":"17524","normalized":[]},{"id":"17542","type":"CID","arg1_id":"17511","arg2_id":"17510","normalized":[]},{"id":"17543","type":"CID","arg1_id":"17511","arg2_id":"17524","normalized":[]}]}
{"id":"17544","document_id":"21418164","passages":[{"id":"17545","type":"title","text":["CCNU (lomustine) toxicity in dogs: a retrospective study (2002-07)."],"offsets":[[0,67]]},{"id":"17546","type":"abstract","text":["OBJECTIVE: To describe the incidence of haematological, renal, hepatic and gastrointestinal toxicities in tumour-bearing dogs receiving 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). DESIGN: The medical records of 206 dogs that were treated with CCNU at the Melbourne Veterinary Specialist Centre between February 2002 and December 2007 were retrospectively evaluated. RESULTS: Of the 206 dogs treated with CCNU, 185 met the inclusion criteria for at least one class of toxicity. CCNU was used most commonly in the treatment of lymphoma, mast cell tumour, brain tumour, histiocytic tumours and epitheliotropic lymphoma. Throughout treatment, 56.9% of dogs experienced neutropenia, 34.2% experienced anaemia and 14.2% experienced thrombocytopenia. Gastrointestinal toxicosis was detected in 37.8% of dogs, the most common sign of which was vomiting (24.3%). Potential renal toxicity and elevated alanine transaminase (ALT) concentration were reported in 12.2% and 48.8% of dogs, respectively. The incidence of hepatic failure was 1.2%. CONCLUSIONS: CCNU-associated toxicity in dogs is common, but is usually not life threatening."],"offsets":[[68,1202]]}],"entities":[{"id":"17547","type":"Chemical","text":["CCNU"],"offsets":[[0,4]],"normalized":[{"db_name":"MESH","db_id":"D008130"}]},{"id":"17548","type":"Chemical","text":["lomustine"],"offsets":[[6,15]],"normalized":[{"db_name":"MESH","db_id":"D008130"}]},{"id":"17549","type":"Disease","text":["toxicity"],"offsets":[[17,25]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"17550","type":"Disease","text":["haematological, renal, hepatic and gastrointestinal toxicities"],"offsets":[[108,170]],"normalized":[{"db_name":"MESH","db_id":"D006402"},{"db_name":"MESH","db_id":"D007674"},{"db_name":"MESH","db_id":"D056486"},{"db_name":"MESH","db_id":"D005767"}]},{"id":"17551","type":"Disease","text":["haematological","toxicities"],"offsets":[[108,122],[160,170]],"normalized":[{"db_name":"MESH","db_id":"D006402"}]},{"id":"17552","type":"Disease","text":["renal","toxicities"],"offsets":[[124,129],[160,170]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"17553","type":"Disease","text":["hepatic","toxicities"],"offsets":[[131,138],[160,170]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"17554","type":"Disease","text":["gastrointestinal 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{"id":"17656","document_id":"9121607","passages":[{"id":"17657","type":"title","text":["Neuroactive steroids protect against pilocarpine- and kainic acid-induced limbic seizures and status epilepticus in mice."],"offsets":[[0,121]]},{"id":"17658","type":"abstract","text":["Several structurally related metabolites of progesterone (3 alpha-hydroxy pregnane-20-ones) and deoxycorticosterone (3 alpha-hydroxy pregnane-21-diol-20-ones) and their 3 beta-epimers were evaluated for protective activity against pilocarpine-, kainic acid- and N-methyl-D-aspartate (NMDA)-induced seizures in mice. Steroids with the 3-hydroxy group in the alpha-position and 5-H in the alpha- or beta-configurations were highly effective in protecting against pilocarpine (416 mg\/kg, s.c.)-induced limbic motor seizures and status epilepticus (ED50 values, 7.0-18.7 mg\/kg, i.p.). The corresponding epimers with the 3-hydroxy group in the beta-position were also effective but less potent (ED50 values, 33.8-63.5, i.p.). Although the neuroactive steroids were considerably less potent than the benzodiazepine clonazepam in protecting against pilocarpine seizures, steroids with the 5 alpha,3 alpha-configuration had comparable or higher protective index values (TD50 for motor impairment divided by ED50 for seizure protection) than clonazepam, indicating that some neuroactive steroids may have lower relative toxicity. Steroids with the 5 alpha,3 alpha- or 5 beta,3 alpha-configurations also produced a dose-dependent delay in the onset of limbic seizures induced by kainic acid (32 mg\/kg, s.c.), but did not completely protect against the seizures. However, when a second dose of the steroid was administered 1 hr after the first dose, complete protection from the kainic acid-induced limbic seizures and status epilepticus was obtained. The steroids also caused a dose-dependent delay in NMDA (257 mg\/kg, s.c.)-induced lethality, but did not completely protect against NMDA seizures or lethality. We conclude that neuroactive steroids are highly effective in protecting against pilocarpine- and kainic acid-induced seizures and status epilepticus in mice, and may be of utility in the treatment of some forms of status epilepticus in humans."],"offsets":[[122,2067]]}],"entities":[{"id":"17659","type":"Chemical","text":["steroids"],"offsets":[[12,20]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"17660","type":"Chemical","text":["pilocarpine"],"offsets":[[37,48]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"17661","type":"Chemical","text":["kainic acid"],"offsets":[[54,65]],"normalized":[{"db_name":"MESH","db_id":"D007608"}]},{"id":"17662","type":"Disease","text":["seizures"],"offsets":[[81,89]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"17663","type":"Disease","text":["status 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{"id":"17855","document_id":"7905523","passages":[{"id":"17856","type":"title","text":["The safety and efficacy of combination N-butyl-deoxynojirimycin (SC-48334) and zidovudine in patients with HIV-1 infection and 200-500 CD4 cells\/mm3."],"offsets":[[0,149]]},{"id":"17857","type":"abstract","text":["We conducted a double-blind, randomized phase II study to evaluate the safety and activity of combination therapy with N-butyl-deoxynojirimycin (SC-48334) (an alpha-glucosidase I inhibitor) and zidovudine versus zidovudine alone. Patients with 200 to 500 CD4 cells\/mm3 who tolerated < or = 12 weeks of prior zidovudine therapy received SC-48334 (1000 mg every 8 h) and zidovudine (100 mg every 8 h) or zidovudine and placebo. Sixty patients received combination therapy and 58, zidovudine and placebo. Twenty-three patients (38%) and 15 (26%), in the combination and zidovudine groups, respectively, discontinued therapy (p = 0.15). The mean SC-48334 steady-state trough level (4.04 +\/- 0.99 micrograms\/ml) was below the in vitro inhibitory concentration for human immunodeficiency virus (HIV). The mean increase in CD4 cells at week 4 was 73.8 cells\/mm3 and 52.4 cells\/mm3 for the combination and zidovudine groups, respectively (p > 0.36). For patients with prior zidovudine therapy, the mean change in CD4 cells in the combination and zidovudine groups was 63.7 cells\/mm3 and 4.9 cells\/mm3 at week 8 and 6.8 cells\/mm3 and -45.1 cells\/mm3 at week 16, respectively. The number of patients with suppression of HIV p24 antigenemia in the combination and zidovudine groups was six (40%) and two (11%) at week 4 (p = 0.10) and five (45%) and two (14%) at week 24 (p = 0.08), respectively. Diarrhea, flatulence, abdominal pain, and weight loss were common for combination recipients.(ABSTRACT TRUNCATED AT 250 WORDS)"],"offsets":[[150,1662]]}],"entities":[{"id":"17858","type":"Chemical","text":["N-butyl-deoxynojirimycin"],"offsets":[[39,63]],"normalized":[{"db_name":"MESH","db_id":"C059896"}]},{"id":"17859","type":"Chemical","text":["SC-48334"],"offsets":[[65,73]],"normalized":[{"db_name":"MESH","db_id":"C059896"}]},{"id":"17860","type":"Chemical","text":["zidovudine"],"offsets":[[79,89]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"17861","type":"Disease","text":["HIV-1 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{"id":"17954","document_id":"3431591","passages":[{"id":"17955","type":"title","text":["Recent preclinical and clinical studies with the thymidylate synthase inhibitor N10-propargyl-5,8-dideazafolic acid (CB 3717)."],"offsets":[[0,126]]},{"id":"17956","type":"abstract","text":["CB 3717, N10-propargyl-5,8-dideazafolic acid, is a tight-binding inhibitor of thymidylate synthase (TS) whose cytotoxicity is mediated solely through the inhibition of this enzyme. Recent preclinical studies have focused on the intracellular formation of CB 3717 polyglutamates. Following a 12-hour exposure of L1210 cells to 50 microM [3H]CB 3717, 30% of the extractable radioactivity could be accounted for as CB 3717 tetra- and pentaglutamate, as determined by high-pressure liquid chromatography (HPLC) analyses. As inhibitors of isolated L1210 TS, CB 3717 di-, tri-, tetra- and pentaglutamate are 26-, 87-, 119- and 114-fold more potent than CB 3717, respectively, and their formation may, therefore, be an important determinant of CB 3717 cytotoxicity. In early clinical studies with CB 3717, activity has been seen in breast cancer, ovarian cancer, hepatoma, and mesothelioma. Toxicities included hepatotoxicity, malaise, and dose-limiting nephrotoxicity. This latter effect is thought to be due to drug precipitation within the renal tubule as a result of the poor solubility of CB 3717 under acidic conditions. In an attempt to overcome this problem, a clinical trial of CB 3717 administered with alkaline diuresis is under way. Preliminary results at 400 and 500 mg\/m2 suggest that a reduction in nephrotoxicity may have been achieved with only 1 instance of renal toxicity in 10 patients. Hepatotoxicity and malaise are again the most frequent side effects. Evidence of antitumor activity has been seen in 3 patients. Pharmacokinetic investigations have shown that alkaline diuresis does not alter CB 3717 plasma levels or urinary excretion and that satisfactory urinary alkalinization can be readily achieved."],"offsets":[[127,1848]]}],"entities":[{"id":"17957","type":"Chemical","text":["N10-propargyl-5,8-dideazafolic acid"],"offsets":[[80,115]],"normalized":[{"db_name":"MESH","db_id":"C031662"}]},{"id":"17958","type":"Chemical","text":["CB 3717"],"offsets":[[117,124]],"normalized":[{"db_name":"MESH","db_id":"C031662"}]},{"id":"17959","type":"Chemical","text":["CB 3717"],"offsets":[[127,134]],"normalized":[{"db_name":"MESH","db_id":"C031662"}]},{"id":"17960","type":"Chemical","text":["N10-propargyl-5,8-dideazafolic acid"],"offsets":[[136,171]],"normalized":[{"db_name":"MESH","db_id":"C031662"}]},{"id":"17961","type":"Disease","text":["cytotoxicity"],"offsets":[[237,249]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"17962","type":"Chemical","text":["CB 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{"id":"18075","document_id":"33969","passages":[{"id":"18076","type":"title","text":["Ethopropazine and benztropine in neuroleptic-induced parkinsonism."],"offsets":[[0,66]]},{"id":"18077","type":"abstract","text":["In a 12-week controlled study ethopropazine was compared to benztropine in the treatment of parkinsonism induced by fluphenazine enanthate in 60 schizophrenic outpatients. Ethopropazine and benztropine were found to be equally effective in controlling parkinsonian symptoms and were as efficacious as procyclidine, their previous antiparkinsonian drug. However, benztropine treated patients had a significant increase in tardive dyskinesia compared to their condition during procyclindine treatment, and significantly more anxiety and depression than ethopropazine treated patients. This suggests that benztropine is not the anticholinergic drug of choice in the treatment of neuroleptic-induced parkinsonian symptoms, because of its more toxic central and peripheral atropinic effect."],"offsets":[[67,852]]}],"entities":[{"id":"18078","type":"Chemical","text":["Ethopropazine"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"C084820"}]},{"id":"18079","type":"Chemical","text":["benztropine"],"offsets":[[18,29]],"normalized":[{"db_name":"MESH","db_id":"D001590"}]},{"id":"18080","type":"Disease","text":["parkinsonism"],"offsets":[[53,65]],"normalized":[{"db_name":"MESH","db_id":"D010302"}]},{"id":"18081","type":"Chemical","text":["ethopropazine"],"offsets":[[97,110]],"normalized":[{"db_name":"MESH","db_id":"C084820"}]},{"id":"18082","type":"Chemical","text":["benztropine"],"offsets":[[127,138]],"normalized":[{"db_name":"MESH","db_id":"D001590"}]},{"id":"18083","type":"Disease","text":["parkinsonism"],"offsets":[[159,171]],"normalized":[{"db_name":"MESH","db_id":"D010302"}]},{"id":"18084","type":"Chemical","text":["fluphenazine enanthate"],"offsets":[[183,205]],"normalized":[{"db_name":"MESH","db_id":"C017610"}]},{"id":"18085","type":"Disease","text":["schizophrenic"],"offsets":[[212,225]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"18086","type":"Chemical","text":["Ethopropazine"],"offsets":[[239,252]],"normalized":[{"db_name":"MESH","db_id":"C084820"}]},{"id":"18087","type":"Chemical","text":["benztropine"],"offsets":[[257,268]],"normalized":[{"db_name":"MESH","db_id":"D001590"}]},{"id":"18088","type":"Disease","text":["parkinsonian symptoms"],"offsets":[[319,340]],"normalized":[{"db_name":"MESH","db_id":"D010302"}]},{"id":"18089","type":"Chemical","text":["procyclidine"],"offsets":[[368,380]],"normalized":[{"db_name":"MESH","db_id":"D011352"}]},{"id":"18090","type":"Chemical","text":["benztropine"],"offsets":[[429,440]],"normalized":[{"db_name":"MESH","db_id":"D001590"}]},{"id":"18091","type":"Disease","text":["tardive dyskinesia"],"offsets":[[488,506]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"18092","type":"Chemical","text":["procyclindine"],"offsets":[[542,555]],"normalized":[{"db_name":"MESH","db_id":"D011352"}]},{"id":"18093","type":"Disease","text":["anxiety"],"offsets":[[590,597]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"18094","type":"Disease","text":["depression"],"offsets":[[602,612]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"18095","type":"Chemical","text":["ethopropazine"],"offsets":[[618,631]],"normalized":[{"db_name":"MESH","db_id":"C084820"}]},{"id":"18096","type":"Chemical","text":["benztropine"],"offsets":[[669,680]],"normalized":[{"db_name":"MESH","db_id":"D001590"}]},{"id":"18097","type":"Disease","text":["parkinsonian symptoms"],"offsets":[[763,784]],"normalized":[{"db_name":"MESH","db_id":"D010302"}]}],"events":[],"coreferences":[],"relations":[{"id":"18098","type":"CID","arg1_id":"18079","arg2_id":"18093","normalized":[]},{"id":"18099","type":"CID","arg1_id":"18082","arg2_id":"18093","normalized":[]},{"id":"18100","type":"CID","arg1_id":"18087","arg2_id":"18093","normalized":[]},{"id":"18101","type":"CID","arg1_id":"18090","arg2_id":"18093","normalized":[]},{"id":"18102","type":"CID","arg1_id":"18096","arg2_id":"18093","normalized":[]},{"id":"18103","type":"CID","arg1_id":"18079","arg2_id":"18094","normalized":[]},{"id":"18104","type":"CID","arg1_id":"18082","arg2_id":"18094","normalized":[]},{"id":"18105","type":"CID","arg1_id":"18087","arg2_id":"18094","normalized":[]},{"id":"18106","type":"CID","arg1_id":"18090","arg2_id":"18094","normalized":[]},{"id":"18107","type":"CID","arg1_id":"18096","arg2_id":"18094","normalized":[]},{"id":"18108","type":"CID","arg1_id":"18079","arg2_id":"18091","normalized":[]},{"id":"18109","type":"CID","arg1_id":"18082","arg2_id":"18091","normalized":[]},{"id":"18110","type":"CID","arg1_id":"18087","arg2_id":"18091","normalized":[]},{"id":"18111","type":"CID","arg1_id":"18090","arg2_id":"18091","normalized":[]},{"id":"18112","type":"CID","arg1_id":"18096","arg2_id":"18091","normalized":[]},{"id":"18113","type":"CID","arg1_id":"18084","arg2_id":"18080","normalized":[]},{"id":"18114","type":"CID","arg1_id":"18084","arg2_id":"18083","normalized":[]},{"id":"18115","type":"CID","arg1_id":"18084","arg2_id":"18088","normalized":[]},{"id":"18116","type":"CID","arg1_id":"18084","arg2_id":"18097","normalized":[]}]}
{"id":"18117","document_id":"16844102","passages":[{"id":"18118","type":"title","text":["Effect of alpha-tocopherol and deferoxamine on methamphetamine-induced neurotoxicity."],"offsets":[[0,85]]},{"id":"18119","type":"abstract","text":["Methamphetamine (MA)-induced dopaminergic neurotoxicity is believed to be associated with the increased formation of free radicals. This study examined the effect of alpha-tocopherol (alpha-TC), a scavenger of reactive oxygen species, and deferoxamine (DFO), an iron chelator, on the MA-induced neurotoxicity. Male rats were treated with MA (10 mg\/kg, every 2 h for four injections). The rat received either alpha-TC (20 mg\/kg) intraperitoneally for 3 days and 30 min prior to MA administration or DFO (50 mg\/kg) subcutaneously 30 min before MA administration. The concentrations of dopamine (DA), serotonin and their metabolites decreased significantly after MA administration, which was inhibited by the alpha-TC and DFO pretreatment. alpha-TC and DFO attenuated the MA-induced hyperthermia as well as the alterations in the locomotor activity. The level of lipid peroxidation was higher and the reduced glutathione concentration was lower in the MA-treated rats. These changes were significantly attenuated by alpha-TC and DFO. This suggests that alpha-TC and DFO ameliorate the MA-induced neuronal damage by decreasing the level of oxidative stress."],"offsets":[[86,1239]]}],"entities":[{"id":"18120","type":"Chemical","text":["alpha-tocopherol"],"offsets":[[10,26]],"normalized":[{"db_name":"MESH","db_id":"D024502"}]},{"id":"18121","type":"Chemical","text":["deferoxamine"],"offsets":[[31,43]],"normalized":[{"db_name":"MESH","db_id":"D003676"}]},{"id":"18122","type":"Chemical","text":["methamphetamine"],"offsets":[[47,62]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"18123","type":"Disease","text":["neurotoxicity"],"offsets":[[71,84]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"18124","type":"Chemical","text":["Methamphetamine"],"offsets":[[86,101]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"18125","type":"Chemical","text":["MA"],"offsets":[[103,105]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"18126","type":"Disease","text":["neurotoxicity"],"offsets":[[128,141]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"18127","type":"Chemical","text":["alpha-tocopherol"],"offsets":[[252,268]],"normalized":[{"db_name":"MESH","db_id":"D024502"}]},{"id":"18128","type":"Chemical","text":["alpha-TC"],"offsets":[[270,278]],"normalized":[{"db_name":"MESH","db_id":"D024502"}]},{"id":"18129","type":"Chemical","text":["oxygen"],"offsets":[[305,311]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"18130","type":"Chemical","text":["deferoxamine"],"offsets":[[325,337]],"normalized":[{"db_name":"MESH","db_id":"D003676"}]},{"id":"18131","type":"Chemical","text":["DFO"],"offsets":[[339,342]],"normalized":[{"db_name":"MESH","db_id":"D003676"}]},{"id":"18132","type":"Chemical","text":["iron"],"offsets":[[348,352]],"normalized":[{"db_name":"MESH","db_id":"D007501"}]},{"id":"18133","type":"Chemical","text":["MA"],"offsets":[[370,372]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"18134","type":"Disease","text":["neurotoxicity"],"offsets":[[381,394]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"18135","type":"Chemical","text":["MA"],"offsets":[[424,426]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"18136","type":"Chemical","text":["alpha-TC"],"offsets":[[494,502]],"normalized":[{"db_name":"MESH","db_id":"D024502"}]},{"id":"18137","type":"Chemical","text":["MA"],"offsets":[[563,565]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"18138","type":"Chemical","text":["DFO"],"offsets":[[584,587]],"normalized":[{"db_name":"MESH","db_id":"D003676"}]},{"id":"18139","type":"Chemical","text":["MA"],"offsets":[[628,630]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"18140","type":"Chemical","text":["dopamine"],"offsets":[[669,677]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"18141","type":"Chemical","text":["DA"],"offsets":[[679,681]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"18142","type":"Chemical","text":["serotonin"],"offsets":[[684,693]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"18143","type":"Chemical","text":["MA"],"offsets":[[746,748]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"18144","type":"Chemical","text":["alpha-TC"],"offsets":[[792,800]],"normalized":[{"db_name":"MESH","db_id":"D024502"}]},{"id":"18145","type":"Chemical","text":["DFO"],"offsets":[[805,808]],"normalized":[{"db_name":"MESH","db_id":"D003676"}]},{"id":"18146","type":"Chemical","text":["alpha-TC"],"offsets":[[823,831]],"normalized":[{"db_name":"MESH","db_id":"D024502"}]},{"id":"18147","type":"Chemical","text":["DFO"],"offsets":[[836,839]],"normalized":[{"db_name":"MESH","db_id":"D003676"}]},{"id":"18148","type":"Chemical","text":["MA"],"offsets":[[855,857]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"18149","type":"Disease","text":["hyperthermia"],"offsets":[[866,878]],"normalized":[{"db_name":"MESH","db_id":"D005334"}]},{"id":"18150","type":"Chemical","text":["glutathione"],"offsets":[[992,1003]],"normalized":[{"db_name":"MESH","db_id":"D005978"}]},{"id":"18151","type":"Chemical","text":["MA"],"offsets":[[1035,1037]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"18152","type":"Chemical","text":["alpha-TC"],"offsets":[[1099,1107]],"normalized":[{"db_name":"MESH","db_id":"D024502"}]},{"id":"18153","type":"Chemical","text":["DFO"],"offsets":[[1112,1115]],"normalized":[{"db_name":"MESH","db_id":"D003676"}]},{"id":"18154","type":"Chemical","text":["alpha-TC"],"offsets":[[1136,1144]],"normalized":[{"db_name":"MESH","db_id":"D024502"}]},{"id":"18155","type":"Chemical","text":["DFO"],"offsets":[[1149,1152]],"normalized":[{"db_name":"MESH","db_id":"D003676"}]},{"id":"18156","type":"Chemical","text":["MA"],"offsets":[[1168,1170]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"18157","type":"Disease","text":["neuronal 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{"id":"18180","document_id":"14633084","passages":[{"id":"18181","type":"title","text":["Use of dexamethasone with mesna for the prevention of ifosfamide-induced hemorrhagic cystitis."],"offsets":[[0,94]]},{"id":"18182","type":"abstract","text":["AIM: Hemorrhagic cystitis (HC) is a limiting side-effect of chemotherapy with ifosfamide (IFS). In the study presented here, we investigated the use of dexamethasone in combination with mesna for the prevention of IFS-induced HC. METHODS: Male Wistar rats (150-200 g; 6 rats per group) were treated with saline or mesna 5 min (i.p.) before and 2 and 6 h after (v.o.) administration of IFS. One, two or three doses of mesna were replaced with dexamethasone alone or with dexamethasone plus mesna. Cystitis was evaluated 24 h after its induction by the changes in bladder wet weight and by macroscopic and microscopic analysis. RESULTS: The replacement of the last dose or the last two doses of mesna with dexamethasone reduced the increase in bladder wet weight induced by IFS by 84.79% and 89.13%, respectively. In addition, it almost abolished the macroscopic and microscopic alterations induced by IFS. Moreover, the addition of dexamethasone to the last two doses of mesna was more efficient than three doses of mesna alone when evaluated microscopically. CONCLUSION: Dexamethasone in combination with mesna was efficient in blocking IFS-induced HC. However, the replacement of last two doses of mesna with saline or all of the mesna doses with dexamethasone did not prevent HC."],"offsets":[[95,1376]]}],"entities":[{"id":"18183","type":"Chemical","text":["dexamethasone"],"offsets":[[7,20]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"18184","type":"Chemical","text":["mesna"],"offsets":[[26,31]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"18185","type":"Chemical","text":["ifosfamide"],"offsets":[[54,64]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"18186","type":"Disease","text":["hemorrhagic 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{"id":"18357","document_id":"11999899","passages":[{"id":"18358","type":"title","text":["Behavioral effects of MK-801 on reserpine-treated mice."],"offsets":[[0,55]]},{"id":"18359","type":"abstract","text":["The effects of dizocilpine (MK-801), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, were studied on dopamine-related behaviors induced by reserpine treatments. This study focuses on behavioral syndromes that may used as models for Parkinson's disease, or tardive dyskinesia, and its response after glutamatergic blockage. Reserpine (1 mg\/kg), administered once every other day for 4 days, produced increases in orofacial dyskinesia, tongue protrusion and vacuous chewing in mice, which are signs indicative of tardive dyskinesia. Reserpine also produced tremor and catalepsy, which are signs suggestive of Parkinson's disease. MK-801 (0.1 mg\/kg), administered 30 min before the observation test, prevented the vacuous chewing movements, tongue protrusions and catalepsy induced by reserpine. However, MK-801 injection produced a significant increase of tremor in reserpine-treated mice. Reserpine (1 mg\/kg), administered 90 min before the test and followed by apomophine injection (0.1 mg\/kg) 5 min before the test, did not produce oral dyskinesia in mice. On the other hand, reserpine induced increases in tremor and catalepsy compared to control mice. MK-801 (0.1 mg\/kg) administration attenuated the catalepsy and tremor induced by reserpine. Pretreatment with reserpine (1 mg\/kg) 24 h before the observation test produced increases in vacuous chewing movements and tongue protrusion, as well as increases in tremor and catalepsy, whereas MK-801 (0.1 mg\/kg) injection 90 min before the test reversed the effects of reserpine. These results show that reserpine produces different and abnormal movements, which are related to dose and schedule employed and can be considered as parkinsonian-like and tardive dsykinesia signs. The glutamatergic blockage produced by NMDA can restore these signs, such as vacuous chewing movements, tongue protrusions, catalepsy and tremor according to the employed model."],"offsets":[[56,1979]]}],"entities":[{"id":"18360","type":"Chemical","text":["MK-801"],"offsets":[[22,28]],"normalized":[{"db_name":"MESH","db_id":"D016291"}]},{"id":"18361","type":"Chemical","text":["reserpine"],"offsets":[[32,41]],"normalized":[{"db_name":"MESH","db_id":"D012110"}]},{"id":"18362","type":"Chemical","text":["dizocilpine"],"offsets":[[71,82]],"normalized":[{"db_name":"MESH","db_id":"D016291"}]},{"id":"18363","type":"Chemical","text":["MK-801"],"offsets":[[84,90]],"normalized":[{"db_name":"MESH","db_id":"D016291"}]},{"id":"18364","type":"Chemical","text":["N-methyl-D-aspartate"],"offsets":[[110,130]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"18365","type":"Chemical","text":["NMDA"],"offsets":[[132,136]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"18366","type":"Chemical","text":["dopamine"],"offsets":[[175,183]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"18367","type":"Chemical","text":["reserpine"],"offsets":[[213,222]],"normalized":[{"db_name":"MESH","db_id":"D012110"}]},{"id":"18368","type":"Disease","text":["Parkinson's 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{"id":"18597","document_id":"9431903","passages":[{"id":"18598","type":"title","text":["Effect of glyceryl trinitrate on the sphincter of Oddi spasm evoked by prostigmine-morphine administration."],"offsets":[[0,107]]},{"id":"18599","type":"abstract","text":["OBJECTIVE: In this study the effect of glyceryl trinitrate on the prostigmine-morphine-induced sphincter of Oddi spasm was evaluated in nine female patients with sphincter of Oddi dyskinesia. METHOD: Sphincter of Oddi spasm was induced by prostigmine-morphine administration (0.5 mg prostigmine intramuscularly and 10 mg morphine subcutaneously) and visualized by quantitative hepatobiliary scintigraphy. The entire procedure was repeated during glyceryl trinitrate infusion (Nitrolingual 1 microg\/kg\/min for 120 min). RESULTS: Prostigmine-morphine provocation caused significant increases in the time to peak activity (Tmax) over the hepatic hilum (HH: 34.33 +\/- 5.05 vs. 22.77 +\/- 3.26) and the common bile duct (CBD: 60.44 +\/- 5.99 vs. 40.0 +\/- 2.88) and in the half-time of excretion (T1\/2) over the liver parenchyma (LP: 120.04 +\/- 16.01 vs. 27.37 +\/- 2.19), HH (117.61 +\/- 14.71 vs. 31.85 +\/- 3.99) and CBD (158.11 +\/- 9.18 vs. 40.1 +\/- 6.24), indicating a complete spasm at the level of the sphincter of Oddi. Glyceryl trinitrate infusion completely normalized the prostigmine-morphine-induced alterations in these quantitative parameters (TmaX over the LP: 11.33 +\/- 1.13; over the HH: 18.88 +\/- 1.48; and over the CBD: 36.22 +\/- 1.92; and T1\/2 over the LP: 28.21 +\/- 1.83; over the HH: 33.42 +\/- 3.10; and over the CBD: 41.66 +\/- 6.33), suggesting an effective sphincter-relaxing effect of glyceryl trinitrate. CONCLUSION: These results provide the first evidence of the effectiveness of glyceryl trinitrate on the morphine-induced sphincter of Oddi spasm in humans. Since glyceryl trinitrate is able to overcome even the drastic effect of morphine, it might be of relevance in the treatment of sphincter of Oddi dyskinesia."],"offsets":[[108,1841]]}],"entities":[{"id":"18600","type":"Chemical","text":["glyceryl trinitrate"],"offsets":[[10,29]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"18601","type":"Disease","text":["sphincter of Oddi spasm"],"offsets":[[37,60]],"normalized":[{"db_name":"MESH","db_id":"D046628"},{"db_name":"MESH","db_id":"D013035"}]},{"id":"18602","type":"Disease","text":["sphincter of Oddi spasm"],"offsets":[[37,60]],"normalized":[{"db_name":"MESH","db_id":"D046628"}]},{"id":"18603","type":"Disease","text":["spasm"],"offsets":[[55,60]],"normalized":[{"db_name":"MESH","db_id":"D013035"}]},{"id":"18604","type":"Chemical","text":["prostigmine"],"offsets":[[71,82]],"normalized":[{"db_name":"MESH","db_id":"D009388"}]},{"id":"18605","type":"Chemical","text":["morphine"],"offsets":[[83,91]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"18606","type":"Chemical","text":["glyceryl trinitrate"],"offsets":[[147,166]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"18607","type":"Chemical","text":["prostigmine"],"offsets":[[174,185]],"normalized":[{"db_name":"MESH","db_id":"D009388"}]},{"id":"18608","type":"Chemical","text":["morphine"],"offsets":[[186,194]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"18609","type":"Disease","text":["sphincter of Oddi spasm"],"offsets":[[203,226]],"normalized":[{"db_name":"MESH","db_id":"D046628"},{"db_name":"MESH","db_id":"D013035"}]},{"id":"18610","type":"Disease","text":["sphincter of Oddi spasm"],"offsets":[[203,226]],"normalized":[{"db_name":"MESH","db_id":"D046628"}]},{"id":"18611","type":"Disease","text":["spasm"],"offsets":[[221,226]],"normalized":[{"db_name":"MESH","db_id":"D013035"}]},{"id":"18612","type":"Disease","text":["sphincter of Oddi dyskinesia"],"offsets":[[270,298]],"normalized":[{"db_name":"MESH","db_id":"D046628"}]},{"id":"18613","type":"Disease","text":["Sphincter of Oddi spasm"],"offsets":[[308,331]],"normalized":[{"db_name":"MESH","db_id":"D046628"},{"db_name":"MESH","db_id":"D013035"}]},{"id":"18614","type":"Disease","text":["Sphincter of Oddi spasm"],"offsets":[[308,331]],"normalized":[{"db_name":"MESH","db_id":"D046628"}]},{"id":"18615","type":"Disease","text":["spasm"],"offsets":[[326,331]],"normalized":[{"db_name":"MESH","db_id":"D013035"}]},{"id":"18616","type":"Chemical","text":["prostigmine"],"offsets":[[347,358]],"normalized":[{"db_name":"MESH","db_id":"D009388"}]},{"id":"18617","type":"Chemical","text":["morphine"],"offsets":[[359,367]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"18618","type":"Chemical","text":["prostigmine"],"offsets":[[391,402]],"normalized":[{"db_name":"MESH","db_id":"D009388"}]},{"id":"18619","type":"Chemical","text":["morphine"],"offsets":[[429,437]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"18620","type":"Chemical","text":["glyceryl trinitrate"],"offsets":[[554,573]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"18621","type":"Chemical","text":["Nitrolingual"],"offsets":[[584,596]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"18622","type":"Chemical","text":["Prostigmine"],"offsets":[[636,647]],"normalized":[{"db_name":"MESH","db_id":"D009388"}]},{"id":"18623","type":"Chemical","text":["morphine"],"offsets":[[648,656]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"18624","type":"Disease","text":["spasm"],"offsets":[[1080,1085]],"normalized":[{"db_name":"MESH","db_id":"D013035"}]},{"id":"18625","type":"Chemical","text":["Glyceryl trinitrate"],"offsets":[[1125,1144]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"18626","type":"Chemical","text":["prostigmine"],"offsets":[[1180,1191]],"normalized":[{"db_name":"MESH","db_id":"D009388"}]},{"id":"18627","type":"Chemical","text":["morphine"],"offsets":[[1192,1200]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"18628","type":"Chemical","text":["glyceryl trinitrate"],"offsets":[[1507,1526]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"18629","type":"Chemical","text":["glyceryl trinitrate"],"offsets":[[1605,1624]],"normalized":[{"db_name":"MESH","db_id":"D005996"}]},{"id":"18630","type":"Chemical","text":["morphine"],"offsets":[[1632,1640]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"18631","type":"Disease","text":["sphincter of Oddi spasm"],"offsets":[[1649,1672]],"normalized":[{"db_name":"MESH","db_id":"D046628"},{"db_name":"MESH","db_id":"D013035"}]},{"id":"18632","type":"Disease","text":["sphincter of Oddi 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{"id":"18903","document_id":"8665051","passages":[{"id":"18904","type":"title","text":["Effects of acute steroid administration on ventilatory and peripheral muscles in rats."],"offsets":[[0,86]]},{"id":"18905","type":"abstract","text":["Occasional case reports have shown that acute myopathy may occur in patients treated with massive doses of corticosteroids. The mechanism of this myopathy is poorly understood. Therefore, 60 male rats were randomly assigned to receive daily injection of saline (C), methylprednisolone (M), or triamcinolone (T) 80 mg\/kg\/d for 5 d. Nutritional intake, measured daily in 15 animals, showed a significant reduction of food intake in the steroid-treated groups (-50 and -79% in M and T, respectively). This was associated with a similar loss in body weight. In the 45 remaining animals, diaphragm contractility and histopathologic features of several muscles were studied. Weights of respiratory and peripheral muscles were similarly decreased after steroid treatment. Maximal twitches of the diaphragm were lower in the C group (653 +\/- 174 g\/cm(2)) than in the M group (837 +\/- 171 g\/cm(2); p < 0.05) and the T group (765 +\/- 145 g\/cm(2), NS). Half-relaxation time was prolonged in both steroid groups, and time to peak tension was longer with M, whereas tetanic tensions were similar. Steroid treatment also induced a leftward shift of the force-frequency curve at 25 and 50 Hz when compared with saline treatment (p < 0.05). ATPase staining of the diaphragm, scalenus medius, and gastrocnemius showed type IIb fiber atrophy in the steroid groups and also diaphragmatic type IIa atrophy with T, whereas histologic examinations revealed a normal muscular pattern with absence of necrosis. Finally, a pair-fed (PF) study, performed in 18 rats (C, T, and PF), showed that muscle atrophy was considerably less pronounced in PF animals than in T-treated animals. We conclude that (1) short-term treatment with massive doses of steroids induced severe respiratory and limb muscle wasting; (2) both types of steroids induced predominantly type IIb atrophy, resulting in the expected alterations in diaphragm contractile properties; (3) neither steroid caused muscle necrosis; (4) type IIb atrophy was not caused by acute nutritional deprivation 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This observation prompted a Phase I clinical study of lometrexol given with folic acid supplementation which has confirmed that the toxicity of lometrexol can be markedly reduced by folic acid supplementation. Thrombocytopenia and mucositis were the major toxicities. There was no clear relationship between clinical toxicity and the extent of plasma folate elevation. Associated studies demonstrated that lometrexol plasma pharmacokinetics were not altered by folic acid administration indicating that supplementation is unlikely to reduce toxicity by enhancing lometrexol plasma clearance. The work described in this report has identified for the first time a clinically acceptable schedule for the administration of a GARFT inhibitor. 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acid"],"offsets":[[1202,1212]],"normalized":[{"db_name":"MESH","db_id":"D005492"}]},{"id":"19089","type":"Disease","text":["toxicity"],"offsets":[[1282,1290]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"19090","type":"Chemical","text":["lometrexol"],"offsets":[[1304,1314]],"normalized":[{"db_name":"MESH","db_id":"C045894"}]},{"id":"19091","type":"Disease","text":["cancer"],"offsets":[[1564,1570]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]}],"events":[],"coreferences":[],"relations":[{"id":"19092","type":"CID","arg1_id":"19063","arg2_id":"19083","normalized":[]},{"id":"19093","type":"CID","arg1_id":"19064","arg2_id":"19083","normalized":[]},{"id":"19094","type":"CID","arg1_id":"19066","arg2_id":"19083","normalized":[]},{"id":"19095","type":"CID","arg1_id":"19069","arg2_id":"19083","normalized":[]},{"id":"19096","type":"CID","arg1_id":"19072","arg2_id":"19083","normalized":[]},{"id":"19097","type":"CID","arg1_id":"19075","arg2_id":"19083","normalized":[]},{"id":"19098","type":"CID","arg1_id":"19077","arg2_id":"19083","normalized":[]},{"id":"19099","type":"CID","arg1_id":"19080","arg2_id":"19083","normalized":[]},{"id":"19100","type":"CID","arg1_id":"19087","arg2_id":"19083","normalized":[]},{"id":"19101","type":"CID","arg1_id":"19090","arg2_id":"19083","normalized":[]},{"id":"19102","type":"CID","arg1_id":"19063","arg2_id":"19082","normalized":[]},{"id":"19103","type":"CID","arg1_id":"19064","arg2_id":"19082","normalized":[]},{"id":"19104","type":"CID","arg1_id":"19066","arg2_id":"19082","normalized":[]},{"id":"19105","type":"CID","arg1_id":"19069","arg2_id":"19082","normalized":[]},{"id":"19106","type":"CID","arg1_id":"19072","arg2_id":"19082","normalized":[]},{"id":"19107","type":"CID","arg1_id":"19075","arg2_id":"19082","normalized":[]},{"id":"19108","type":"CID","arg1_id":"19077","arg2_id":"19082","normalized":[]},{"id":"19109","type":"CID","arg1_id":"19080","arg2_id":"19082","normalized":[]},{"id":"19110","type":"CID","arg1_id":"19087","arg2_id":"19082","normalized":[]},{"id":"19111","type":"CID","arg1_id":"19090","arg2_id":"19082","normalized":[]}]}
{"id":"19112","document_id":"2557556","passages":[{"id":"19113","type":"title","text":["Involvement of the mu-opiate receptor in peripheral analgesia."],"offsets":[[0,62]]},{"id":"19114","type":"abstract","text":["The intradermal injection of mu (morphine, Tyr-D-Ala-Gly-NMe-Phe-Gly-ol and morphiceptin), kappa (trans-3,4-dichloro-N-methyl-N[2-(1-pyrrolidinyl) cyclohexyl]benzeneactemide) and delta ([D-Pen2.5]-enkephalin and [D-Ser2]-[Leu]enkephalin-Thr) selective opioid-agonists, by themselves, did not significantly affect the mechanical nociceptive threshold in the hindpaw of the rat. Intradermal injection of mu, but not delta or kappa opioid-agonists, however, produced dose-dependent inhibition of prostaglandin E2-induced hyperalgesia. The analgesic effect of the mu-agonist morphine was dose-dependently antagonized by naloxone and prevented by co-injection of pertussis toxin. Morphine did not, however, alter the hyperalgesia induced by 8-bromo cyclic adenosine monophosphate. We conclude that the analgesic action of opioids on the peripheral terminals of primary afferents is via a binding site with characteristics of the mu-opioid receptor and that this action is mediated by inhibition of the cyclic adenosine monophosphate second messenger system."],"offsets":[[63,1115]]}],"entities":[{"id":"19115","type":"Disease","text":["analgesia"],"offsets":[[52,61]],"normalized":[{"db_name":"MESH","db_id":"D000699"}]},{"id":"19116","type":"Chemical","text":["morphine"],"offsets":[[96,104]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"19117","type":"Chemical","text":["Tyr-D-Ala-Gly-NMe-Phe-Gly-ol"],"offsets":[[106,134]],"normalized":[{"db_name":"MESH","db_id":"D020875"}]},{"id":"19118","type":"Chemical","text":["morphiceptin"],"offsets":[[139,151]],"normalized":[{"db_name":"MESH","db_id":"C028889"}]},{"id":"19119","type":"Chemical","text":["trans-3,4-dichloro-N-methyl-N[2-(1-pyrrolidinyl) cyclohexyl]benzeneactemide"],"offsets":[[161,236]],"normalized":[{"db_name":"MESH","db_id":"D019900"}]},{"id":"19120","type":"Chemical","text":["[D-Pen2.5]-enkephalin"],"offsets":[[249,270]],"normalized":[{"db_name":"MESH","db_id":"D020881"}]},{"id":"19121","type":"Chemical","text":["[D-Ser2]-[Leu]enkephalin-Thr"],"offsets":[[275,303]],"normalized":[{"db_name":"MESH","db_id":"C034318"}]},{"id":"19122","type":"Chemical","text":["prostaglandin E2"],"offsets":[[556,572]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"19123","type":"Disease","text":["hyperalgesia"],"offsets":[[581,593]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"19124","type":"Chemical","text":["morphine"],"offsets":[[634,642]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"19125","type":"Chemical","text":["naloxone"],"offsets":[[679,687]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"19126","type":"Chemical","text":["Morphine"],"offsets":[[738,746]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"19127","type":"Disease","text":["hyperalgesia"],"offsets":[[775,787]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"19128","type":"Chemical","text":["8-bromo cyclic adenosine monophosphate"],"offsets":[[799,837]],"normalized":[{"db_name":"MESH","db_id":"D015124"}]},{"id":"19129","type":"Chemical","text":["cyclic adenosine monophosphate"],"offsets":[[1060,1090]],"normalized":[{"db_name":"MESH","db_id":"D000242"}]}],"events":[],"coreferences":[],"relations":[{"id":"19130","type":"CID","arg1_id":"19128","arg2_id":"19123","normalized":[]},{"id":"19131","type":"CID","arg1_id":"19128","arg2_id":"19127","normalized":[]},{"id":"19132","type":"CID","arg1_id":"19122","arg2_id":"19123","normalized":[]},{"id":"19133","type":"CID","arg1_id":"19122","arg2_id":"19127","normalized":[]}]}
{"id":"19134","document_id":"15580403","passages":[{"id":"19135","type":"title","text":["Adequate timing of ribavirin reduction in patients with hemolysis during combination therapy of interferon and ribavirin for chronic hepatitis C."],"offsets":[[0,145]]},{"id":"19136","type":"abstract","text":["BACKGROUND: Hemolytic anemia is one of the major adverse events of the combination therapy of interferon and ribavirin. Because of ribavirin-related hemolytic anemia, dose reduction is a common event in this therapy. In this clinical retrospective cohort study we have examined the suitable timing of ribavirin reduction in patients with hemolysis during combination therapy. METHODS: Thirty-seven of 160 patients who had HCV-genotype 1b, had high virus load, and received 24-week combination therapy developed anemia with hemoglobin level <10 g\/dl or anemia-related signs during therapy. After that, these 37 patients were reduced one tablet of ribavirin (200 mg) per day. After reduction of ribavirin, 27 of 37 patients could continue combination therapy for a total of 24 weeks (group A). However, 10 of 37 patients with reduction of ribavirin could not continue combination therapy because their <8.5 g\/dl hemoglobin values decreased to or anemia-related severe side effects occurred (group B). We assessed the final efficacy and safety after reduction of ribavirin in groups A and B. RESULTS: A sustained virological response (SVR) was 29.6% (8\/27) in group A and 10% (1\/10) in group B, respectively. A 34.4% (12\/27) of SVR + biological response in group A was higher than 10% (1\/10) in group B ( P = 0.051), with slight significance. With respect to hemoglobin level at the time of ribavirin reduction, a rate of continuation of therapy in patients with > or =10 g\/dl hemoglobin was higher than that in patients with <10 g\/dl ( P = 0.036). CONCLUSIONS: Reduction of ribavirin at hemoglobin level > or =10 g\/dl is suitable in terms of efficacy and side effects."],"offsets":[[146,1812]]}],"entities":[{"id":"19137","type":"Chemical","text":["ribavirin"],"offsets":[[19,28]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"19138","type":"Disease","text":["hemolysis"],"offsets":[[56,65]],"normalized":[{"db_name":"MESH","db_id":"D006461"}]},{"id":"19139","type":"Chemical","text":["interferon"],"offsets":[[96,106]],"normalized":[{"db_name":"MESH","db_id":"D007372"}]},{"id":"19140","type":"Chemical","text":["ribavirin"],"offsets":[[111,120]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"19141","type":"Disease","text":["chronic hepatitis C"],"offsets":[[125,144]],"normalized":[{"db_name":"MESH","db_id":"D019698"}]},{"id":"19142","type":"Disease","text":["Hemolytic anemia"],"offsets":[[158,174]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"19143","type":"Chemical","text":["interferon"],"offsets":[[240,250]],"normalized":[{"db_name":"MESH","db_id":"D007372"}]},{"id":"19144","type":"Chemical","text":["ribavirin"],"offsets":[[255,264]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"19145","type":"Chemical","text":["ribavirin"],"offsets":[[277,286]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"19146","type":"Disease","text":["hemolytic anemia"],"offsets":[[295,311]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"19147","type":"Chemical","text":["ribavirin"],"offsets":[[447,456]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"19148","type":"Disease","text":["hemolysis"],"offsets":[[484,493]],"normalized":[{"db_name":"MESH","db_id":"D006461"}]},{"id":"19149","type":"Disease","text":["anemia"],"offsets":[[657,663]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"19150","type":"Disease","text":["anemia"],"offsets":[[698,704]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"19151","type":"Chemical","text":["ribavirin"],"offsets":[[792,801]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"19152","type":"Chemical","text":["ribavirin"],"offsets":[[839,848]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"19153","type":"Chemical","text":["ribavirin"],"offsets":[[983,992]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"19154","type":"Disease","text":["anemia"],"offsets":[[1090,1096]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"19155","type":"Chemical","text":["ribavirin"],"offsets":[[1206,1215]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"19156","type":"Chemical","text":["ribavirin"],"offsets":[[1534,1543]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]},{"id":"19157","type":"Chemical","text":["ribavirin"],"offsets":[[1718,1727]],"normalized":[{"db_name":"MESH","db_id":"D012254"}]}],"events":[],"coreferences":[],"relations":[{"id":"19158","type":"CID","arg1_id":"19139","arg2_id":"19142","normalized":[]},{"id":"19159","type":"CID","arg1_id":"19139","arg2_id":"19146","normalized":[]},{"id":"19160","type":"CID","arg1_id":"19143","arg2_id":"19142","normalized":[]},{"id":"19161","type":"CID","arg1_id":"19143","arg2_id":"19146","normalized":[]},{"id":"19162","type":"CID","arg1_id":"19137","arg2_id":"19142","normalized":[]},{"id":"19163","type":"CID","arg1_id":"19137","arg2_id":"19146","normalized":[]},{"id":"19164","type":"CID","arg1_id":"19140","arg2_id":"19142","normalized":[]},{"id":"19165","type":"CID","arg1_id":"19140","arg2_id":"19146","normalized":[]},{"id":"19166","type":"CID","arg1_id":"19144","arg2_id":"19142","normalized":[]},{"id":"19167","type":"CID","arg1_id":"19144","arg2_id":"19146","normalized":[]},{"id":"19168","type":"CID","arg1_id":"19145","arg2_id":"19142","normalized":[]},{"id":"19169","type":"CID","arg1_id":"19145","arg2_id":"19146","normalized":[]},{"id":"19170","type":"CID","arg1_id":"19147","arg2_id":"19142","normalized":[]},{"id":"19171","type":"CID","arg1_id":"19147","arg2_id":"19146","normalized":[]},{"id":"19172","type":"CID","arg1_id":"19151","arg2_id":"19142","normalized":[]},{"id":"19173","type":"CID","arg1_id":"19151","arg2_id":"19146","normalized":[]},{"id":"19174","type":"CID","arg1_id":"19152","arg2_id":"19142","normalized":[]},{"id":"19175","type":"CID","arg1_id":"19152","arg2_id":"19146","normalized":[]},{"id":"19176","type":"CID","arg1_id":"19153","arg2_id":"19142","normalized":[]},{"id":"19177","type":"CID","arg1_id":"19153","arg2_id":"19146","normalized":[]},{"id":"19178","type":"CID","arg1_id":"19155","arg2_id":"19142","normalized":[]},{"id":"19179","type":"CID","arg1_id":"19155","arg2_id":"19146","normalized":[]},{"id":"19180","type":"CID","arg1_id":"19156","arg2_id":"19142","normalized":[]},{"id":"19181","type":"CID","arg1_id":"19156","arg2_id":"19146","normalized":[]},{"id":"19182","type":"CID","arg1_id":"19157","arg2_id":"19142","normalized":[]},{"id":"19183","type":"CID","arg1_id":"19157","arg2_id":"19146","normalized":[]}]}
{"id":"19184","document_id":"15075188","passages":[{"id":"19185","type":"title","text":["Increased expression and apical targeting of renal ENaC subunits in puromycin aminonucleoside-induced nephrotic syndrome in rats."],"offsets":[[0,129]]},{"id":"19186","type":"abstract","text":["Nephrotic syndrome is often accompanied by sodium retention and generalized edema. However, the molecular basis for the decreased renal sodium excretion remains undefined. We hypothesized that epithelial Na channel (ENaC) subunit dysregulation may be responsible for the increased sodium retention. An experimental group of rats was treated with puromycin aminonucleoside (PAN; 180 mg\/kg iv), whereas the control group received only vehicle. After 7 days, PAN treatment induced significant proteinuria, hypoalbuminemia, decreased urinary sodium excretion, and extensive ascites. The protein abundance of alpha-ENaC and beta-ENaC was increased in the inner stripe of the outer medulla (ISOM) and in the inner medulla (IM) but was not altered in the cortex. gamma-ENaC abundance was increased in the cortex, ISOM, and IM. Immunoperoxidase brightfield- and laser-scanning confocal fluorescence microscopy demonstrated increased targeting of alpha-ENaC, beta-ENaC, and gamma-ENaC subunits to the apical plasma membrane in the distal convoluted tubule (DCT2), connecting tubule, and cortical and medullary collecting duct segments. Immunoelectron microscopy further revealed an increased labeling of alpha-ENaC in the apical plasma membrane of cortical collecting duct principal cells of PAN-treated rats, indicating enhanced apical targeting of alpha-ENaC subunits. In contrast, the protein abundances of Na(+)\/H(+) exchanger type 3 (NHE3), Na(+)-K(+)-2Cl(-) cotransporter (BSC-1), and thiazide-sensitive Na(+)-Cl(-) cotransporter (TSC) were decreased. Moreover, the abundance of the alpha(1)-subunit of the Na-K-ATPase was decreased in the cortex and ISOM, but it remained unchanged in the IM. In conclusion, the increased or sustained expression of ENaC subunits combined with increased apical targeting in the DCT2, connecting tubule, and collecting duct are likely to play a role in the sodium retention associated with PAN-induced nephrotic syndrome. The decreased abundance of NHE3, BSC-1, TSC, and Na-K-ATPase may play a compensatory role to promote sodium excretion."],"offsets":[[130,2200]]}],"entities":[{"id":"19187","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[68,93]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"19188","type":"Disease","text":["nephrotic syndrome"],"offsets":[[102,120]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]},{"id":"19189","type":"Disease","text":["Nephrotic syndrome"],"offsets":[[130,148]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]},{"id":"19190","type":"Chemical","text":["sodium"],"offsets":[[173,179]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"19191","type":"Disease","text":["edema"],"offsets":[[206,211]],"normalized":[{"db_name":"MESH","db_id":"D004487"}]},{"id":"19192","type":"Chemical","text":["sodium"],"offsets":[[266,272]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"19193","type":"Chemical","text":["Na"],"offsets":[[334,336]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"19194","type":"Chemical","text":["sodium"],"offsets":[[411,417]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"19195","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[476,501]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"19196","type":"Chemical","text":["PAN"],"offsets":[[503,506]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"19197","type":"Chemical","text":["PAN"],"offsets":[[586,589]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"19198","type":"Disease","text":["proteinuria"],"offsets":[[620,631]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"19199","type":"Disease","text":["hypoalbuminemia"],"offsets":[[633,648]],"normalized":[{"db_name":"MESH","db_id":"D034141"}]},{"id":"19200","type":"Chemical","text":["sodium"],"offsets":[[668,674]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"19201","type":"Disease","text":["ascites"],"offsets":[[700,707]],"normalized":[{"db_name":"MESH","db_id":"D001201"}]},{"id":"19202","type":"Chemical","text":["PAN"],"offsets":[[1413,1416]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"19203","type":"Chemical","text":["Na"],"offsets":[[1531,1533]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"19204","type":"Chemical","text":["H"],"offsets":[[1537,1538]],"normalized":[{"db_name":"MESH","db_id":"D006859"}]},{"id":"19205","type":"Chemical","text":["Na"],"offsets":[[1567,1569]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"19206","type":"Chemical","text":["K"],"offsets":[[1573,1574]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"19207","type":"Chemical","text":["Cl"],"offsets":[[1579,1581]],"normalized":[{"db_name":"MESH","db_id":"D002713"}]},{"id":"19208","type":"Chemical","text":["thiazide"],"offsets":[[1612,1620]],"normalized":[{"db_name":"MESH","db_id":"D049971"}]},{"id":"19209","type":"Chemical","text":["Na"],"offsets":[[1631,1633]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"19210","type":"Chemical","text":["Cl"],"offsets":[[1637,1639]],"normalized":[{"db_name":"MESH","db_id":"D002713"}]},{"id":"19211","type":"Chemical","text":["Na"],"offsets":[[1734,1736]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"19212","type":"Chemical","text":["K"],"offsets":[[1737,1738]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"19213","type":"Chemical","text":["sodium"],"offsets":[[2017,2023]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"19214","type":"Chemical","text":["PAN"],"offsets":[[2050,2053]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"19215","type":"Disease","text":["nephrotic 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{"id":"19255","document_id":"14745746","passages":[{"id":"19256","type":"title","text":["Does hormone therapy for the treatment of breast cancer have a detrimental effect on memory and cognition? A pilot study."],"offsets":[[0,121]]},{"id":"19257","type":"abstract","text":["This pilot study examines whether hormone therapy for breast cancer affects cognition. Patients participating in a randomised trial of anastrozole, tamoxifen alone or combined (ATAC) (n=94) and a group of women without breast cancer (n=35) completed a battery of neuropsychological measures. Compared with the control group, the patients were impaired on a processing speed task (p=0.032) and on a measure of immediate verbal memory (p=0.026) after controlling for the use of hormone replacement therapy in both groups. Patient group performance was not significantly related to length of treatment or measures of psychological morbidity. The results showed specific impairments in processing speed and verbal memory in women receiving hormonal therapy for the treatment of breast cancer. Verbal memory may be especially sensitive to changes in oestrogen levels, a finding commonly reported in studies of hormone replacement therapy in healthy women. In view of the increased use of hormone therapies in an adjuvant and preventative setting their impact on cognitive functioning should be investigated more thoroughly."],"offsets":[[122,1240]]}],"entities":[{"id":"19258","type":"Disease","text":["breast cancer"],"offsets":[[42,55]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"19259","type":"Disease","text":["detrimental effect on memory and cognition"],"offsets":[[63,105]],"normalized":[{"db_name":"MESH","db_id":"D008569"},{"db_name":"MESH","db_id":"D003072"}]},{"id":"19260","type":"Disease","text":["detrimental effect on memory"],"offsets":[[63,91]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"19261","type":"Disease","text":["detrimental effect on","cognition"],"offsets":[[63,84],[96,105]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"19262","type":"Disease","text":["breast cancer"],"offsets":[[176,189]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"19263","type":"Chemical","text":["anastrozole"],"offsets":[[257,268]],"normalized":[{"db_name":"MESH","db_id":"C090450"}]},{"id":"19264","type":"Chemical","text":["tamoxifen"],"offsets":[[270,279]],"normalized":[{"db_name":"MESH","db_id":"D013629"}]},{"id":"19265","type":"Disease","text":["breast cancer"],"offsets":[[341,354]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"19266","type":"Disease","text":["breast cancer"],"offsets":[[896,909]],"normalized":[{"db_name":"MESH","db_id":"D001943"}]},{"id":"19267","type":"Chemical","text":["oestrogen"],"offsets":[[967,976]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]}],"events":[],"coreferences":[],"relations":[{"id":"19268","type":"CID","arg1_id":"19264","arg2_id":"19259","normalized":[]},{"id":"19269","type":"CID","arg1_id":"19264","arg2_id":"19260","normalized":[]},{"id":"19270","type":"CID","arg1_id":"19263","arg2_id":"19259","normalized":[]},{"id":"19271","type":"CID","arg1_id":"19263","arg2_id":"19260","normalized":[]},{"id":"19272","type":"CID","arg1_id":"19263","arg2_id":"19259","normalized":[]},{"id":"19273","type":"CID","arg1_id":"19263","arg2_id":"19261","normalized":[]},{"id":"19274","type":"CID","arg1_id":"19264","arg2_id":"19259","normalized":[]},{"id":"19275","type":"CID","arg1_id":"19264","arg2_id":"19261","normalized":[]}]}
{"id":"19276","document_id":"11208990","passages":[{"id":"19277","type":"title","text":["Association of nitric oxide production and apoptosis in a model of experimental nephropathy."],"offsets":[[0,92]]},{"id":"19278","type":"abstract","text":["BACKGROUND: In recent studies increased amounts of nitric oxide (NO) and apoptosis have been implicated in various pathological conditions in the kidney. We have studied the role of NO and its association with apoptosis in an experimental model of nephrotic syndrome induced by a single injection of adriamycin (ADR). METHODS: The alteration in the NO pathway was assessed by measuring nitrite levels in serum\/urine and by evaluating the changes in vascular reactivity of the isolated perfused rat kidney (IPRK) system. Rats were stratified into control groups and ADR-induced nephropathy groups. These two groups were then divided into: group 1, animals receiving saline; and group 2, animals receiving aminoguanidine (AG) which is a specific inhibitor of inducible-NO synthase. On day 21, rats were sacrificed after obtaining material for biochemical analysis. RESULTS: Histopathological examination of the kidneys of rats treated with ADR revealed focal areas of mesangial proliferation and mild tubulointerstitial inflammation. They also had significantly higher levels of proteinuria compared with control and treatment groups (P < 0.05). Urine nitrite levels were significantly increased in the ADR-nephropathy group (P < 0.05). In the IPRK phenylephrine and acetylcholine related responses were significantly impaired in the ADR-nephropathy group. Apoptosis was not detected in controls. However, in the ADR-nephropathy group, numerous apoptotic cells were identified in the tubulointerstitial areas. Double staining revealed numerous interstitial apoptotic cells to stain for ED1, a marker for monocytes\/macrophages. Treatment with AG prevented the impairment of renal vascular bed responses and reduced both urine nitrite levels and apoptosis to control levels. CONCLUSION: We suggest that interactions between NO and apoptosis are important in the pathogenesis of the ADR-induced nephrosis."],"offsets":[[93,1993]]}],"entities":[{"id":"19279","type":"Chemical","text":["nitric oxide"],"offsets":[[15,27]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"19280","type":"Disease","text":["nephropathy"],"offsets":[[80,91]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"19281","type":"Chemical","text":["nitric oxide"],"offsets":[[144,156]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"19282","type":"Chemical","text":["NO"],"offsets":[[158,160]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"19283","type":"Chemical","text":["NO"],"offsets":[[275,277]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"19284","type":"Disease","text":["nephrotic 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proliferation"],"offsets":[[1059,1082]],"normalized":[{"db_name":"MESH","db_id":"C537346"}]},{"id":"19296","type":"Disease","text":["tubulointerstitial inflammation"],"offsets":[[1092,1123]],"normalized":[{"db_name":"MESH","db_id":"D009395"}]},{"id":"19297","type":"Disease","text":["proteinuria"],"offsets":[[1170,1181]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"19298","type":"Chemical","text":["nitrite"],"offsets":[[1243,1250]],"normalized":[{"db_name":"MESH","db_id":"D009573"}]},{"id":"19299","type":"Chemical","text":["ADR"],"offsets":[[1294,1297]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"19300","type":"Disease","text":["nephropathy"],"offsets":[[1298,1309]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"19301","type":"Chemical","text":["phenylephrine"],"offsets":[[1340,1353]],"normalized":[{"db_name":"MESH","db_id":"D010656"}]},{"id":"19302","type":"Chemical","text":["acetylcholine"],"offsets":[[1358,1371]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"19303","type":"Chemical","text":["ADR"],"offsets":[[1425,1428]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"19304","type":"Disease","text":["nephropathy"],"offsets":[[1429,1440]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"19305","type":"Chemical","text":["ADR"],"offsets":[[1504,1507]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"19306","type":"Disease","text":["nephropathy"],"offsets":[[1508,1519]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"19307","type":"Chemical","text":["AG"],"offsets":[[1733,1735]],"normalized":[{"db_name":"MESH","db_id":"C004479"}]},{"id":"19308","type":"Chemical","text":["nitrite"],"offsets":[[1816,1823]],"normalized":[{"db_name":"MESH","db_id":"D009573"}]},{"id":"19309","type":"Chemical","text":["NO"],"offsets":[[1913,1915]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"19310","type":"Chemical","text":["ADR"],"offsets":[[1971,1974]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"19311","type":"Disease","text":["nephrosis"],"offsets":[[1983,1992]],"normalized":[{"db_name":"MESH","db_id":"D009401"}]}],"events":[],"coreferences":[],"relations":[{"id":"19312","type":"CID","arg1_id":"19285","arg2_id":"19297","normalized":[]},{"id":"19313","type":"CID","arg1_id":"19286","arg2_id":"19297","normalized":[]},{"id":"19314","type":"CID","arg1_id":"19289","arg2_id":"19297","normalized":[]},{"id":"19315","type":"CID","arg1_id":"19294","arg2_id":"19297","normalized":[]},{"id":"19316","type":"CID","arg1_id":"19299","arg2_id":"19297","normalized":[]},{"id":"19317","type":"CID","arg1_id":"19303","arg2_id":"19297","normalized":[]},{"id":"19318","type":"CID","arg1_id":"19305","arg2_id":"19297","normalized":[]},{"id":"19319","type":"CID","arg1_id":"19310","arg2_id":"19297","normalized":[]},{"id":"19320","type":"CID","arg1_id":"19285","arg2_id":"19284","normalized":[]},{"id":"19321","type":"CID","arg1_id":"19286","arg2_id":"19284","normalized":[]},{"id":"19322","type":"CID","arg1_id":"19289","arg2_id":"19284","normalized":[]},{"id":"19323","type":"CID","arg1_id":"19294","arg2_id":"19284","normalized":[]},{"id":"19324","type":"CID","arg1_id":"19299","arg2_id":"19284","normalized":[]},{"id":"19325","type":"CID","arg1_id":"19303","arg2_id":"19284","normalized":[]},{"id":"19326","type":"CID","arg1_id":"19305","arg2_id":"19284","normalized":[]},{"id":"19327","type":"CID","arg1_id":"19310","arg2_id":"19284","normalized":[]}]}
{"id":"19328","document_id":"9201797","passages":[{"id":"19329","type":"title","text":["The attenuating effect of carteolol hydrochloride, a beta-adrenoceptor antagonist, on neuroleptic-induced catalepsy in rats."],"offsets":[[0,124]]},{"id":"19330","type":"abstract","text":["It is known that beta-adrenoceptor antagonists are effective in the treatment of akathisia, one of the extrapyramidal side effects that occur during neuroleptic treatment. Neuroleptic-induced catalepsy, a model of neuroleptic-induced extrapyramidal side effects, was considered suitable as a model for predicting neuroleptic-induced akathisia in humans, although neuroleptic-induced catalepsy was not considered a specific test for neuroleptic-induced akathisia. Therefore, the effects of carteolol, a beta-adrenoceptor antagonist, on haloperidol-induced catalepsy in rats were behaviorally studied and compared with those of propranolol and biperiden, a muscarinic receptor antagonist. Carteolol, as well as propranolol and biperiden, inhibited the haloperidol-induced catalepsy. The inhibitory effect of carteolol was almost comparable to that of propranolol, but was weaker than that of biperiden. Carteolol did not evoke postsynaptic dopamine receptor-stimulating behavioral signs such as stereotypy and hyperlocomotion in rats. Carteolol did not antagonize the inhibitory effects of haloperidol on apomorphine-induced stereotypy and locomotor activity in rats. In addition, carteolol did not evoke 5-HT1A receptor-stimulating behavioral signs such as flat body posture and forepaw treading and did not inhibit 5-hydroxytryptophan-induced head twitch in rats. Finally, carteolol did not inhibit physostigmine-induced lethality in rats. These results strongly suggest that carteolol improves haloperidol-induced catalepsy via its beta-adrenoceptor antagonistic activity and is expected to be effective in the treatment of akathisia without attenuating neuroleptic-induced antipsychotic effects due to its postsynaptic dopamine receptor antagonistic activity."],"offsets":[[125,1886]]}],"entities":[{"id":"19331","type":"Chemical","text":["carteolol hydrochloride"],"offsets":[[26,49]],"normalized":[{"db_name":"MESH","db_id":"D002354"}]},{"id":"19332","type":"Disease","text":["catalepsy"],"offsets":[[106,115]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"19333","type":"Disease","text":["akathisia"],"offsets":[[206,215]],"normalized":[{"db_name":"MESH","db_id":"D017109"}]},{"id":"19334","type":"Disease","text":["catalepsy"],"offsets":[[317,326]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"19335","type":"Disease","text":["akathisia"],"offsets":[[458,467]],"normalized":[{"db_name":"MESH","db_id":"D017109"}]},{"id":"19336","type":"Disease","text":["catalepsy"],"offsets":[[508,517]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"19337","type":"Disease","text":["akathisia"],"offsets":[[577,586]],"normalized":[{"db_name":"MESH","db_id":"D017109"}]},{"id":"19338","type":"Chemical","text":["carteolol"],"offsets":[[614,623]],"normalized":[{"db_name":"MESH","db_id":"D002354"}]},{"id":"19339","type":"Chemical","text":["haloperidol"],"offsets":[[660,671]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"19340","type":"Disease","text":["catalepsy"],"offsets":[[680,689]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"19341","type":"Chemical","text":["propranolol"],"offsets":[[751,762]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"19342","type":"Chemical","text":["biperiden"],"offsets":[[767,776]],"normalized":[{"db_name":"MESH","db_id":"D001712"}]},{"id":"19343","type":"Chemical","text":["Carteolol"],"offsets":[[812,821]],"normalized":[{"db_name":"MESH","db_id":"D002354"}]},{"id":"19344","type":"Chemical","text":["propranolol"],"offsets":[[834,845]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"19345","type":"Chemical","text":["biperiden"],"offsets":[[850,859]],"normalized":[{"db_name":"MESH","db_id":"D001712"}]},{"id":"19346","type":"Chemical","text":["haloperidol"],"offsets":[[875,886]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"19347","type":"Disease","text":["catalepsy"],"offsets":[[895,904]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"19348","type":"Chemical","text":["carteolol"],"offsets":[[931,940]],"normalized":[{"db_name":"MESH","db_id":"D002354"}]},{"id":"19349","type":"Chemical","text":["propranolol"],"offsets":[[974,985]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"19350","type":"Chemical","text":["biperiden"],"offsets":[[1015,1024]],"normalized":[{"db_name":"MESH","db_id":"D001712"}]},{"id":"19351","type":"Chemical","text":["Carteolol"],"offsets":[[1026,1035]],"normalized":[{"db_name":"MESH","db_id":"D002354"}]},{"id":"19352","type":"Chemical","text":["dopamine"],"offsets":[[1063,1071]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"19353","type":"Disease","text":["hyperlocomotion"],"offsets":[[1133,1148]],"normalized":[{"db_name":"MESH","db_id":"D009069"}]},{"id":"19354","type":"Chemical","text":["Carteolol"],"offsets":[[1158,1167]],"normalized":[{"db_name":"MESH","db_id":"D002354"}]},{"id":"19355","type":"Chemical","text":["haloperidol"],"offsets":[[1213,1224]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"19356","type":"Chemical","text":["apomorphine"],"offsets":[[1228,1239]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"19357","type":"Chemical","text":["carteolol"],"offsets":[[1304,1313]],"normalized":[{"db_name":"MESH","db_id":"D002354"}]},{"id":"19358","type":"Chemical","text":["5-hydroxytryptophan"],"offsets":[[1440,1459]],"normalized":[{"db_name":"MESH","db_id":"D006916"}]},{"id":"19359","type":"Chemical","text":["carteolol"],"offsets":[[1498,1507]],"normalized":[{"db_name":"MESH","db_id":"D002354"}]},{"id":"19360","type":"Chemical","text":["physostigmine"],"offsets":[[1524,1537]],"normalized":[{"db_name":"MESH","db_id":"D010830"}]},{"id":"19361","type":"Chemical","text":["carteolol"],"offsets":[[1601,1610]],"normalized":[{"db_name":"MESH","db_id":"D002354"}]},{"id":"19362","type":"Chemical","text":["haloperidol"],"offsets":[[1620,1631]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"19363","type":"Disease","text":["catalepsy"],"offsets":[[1640,1649]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"19364","type":"Disease","text":["akathisia"],"offsets":[[1750,1759]],"normalized":[{"db_name":"MESH","db_id":"D017109"}]},{"id":"19365","type":"Chemical","text":["dopamine"],"offsets":[[1846,1854]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]}],"events":[],"coreferences":[],"relations":[{"id":"19366","type":"CID","arg1_id":"19339","arg2_id":"19332","normalized":[]},{"id":"19367","type":"CID","arg1_id":"19339","arg2_id":"19334","normalized":[]},{"id":"19368","type":"CID","arg1_id":"19339","arg2_id":"19336","normalized":[]},{"id":"19369","type":"CID","arg1_id":"19339","arg2_id":"19340","normalized":[]},{"id":"19370","type":"CID","arg1_id":"19339","arg2_id":"19347","normalized":[]},{"id":"19371","type":"CID","arg1_id":"19339","arg2_id":"19363","normalized":[]},{"id":"19372","type":"CID","arg1_id":"19346","arg2_id":"19332","normalized":[]},{"id":"19373","type":"CID","arg1_id":"19346","arg2_id":"19334","normalized":[]},{"id":"19374","type":"CID","arg1_id":"19346","arg2_id":"19336","normalized":[]},{"id":"19375","type":"CID","arg1_id":"19346","arg2_id":"19340","normalized":[]},{"id":"19376","type":"CID","arg1_id":"19346","arg2_id":"19347","normalized":[]},{"id":"19377","type":"CID","arg1_id":"19346","arg2_id":"19363","normalized":[]},{"id":"19378","type":"CID","arg1_id":"19355","arg2_id":"19332","normalized":[]},{"id":"19379","type":"CID","arg1_id":"19355","arg2_id":"19334","normalized":[]},{"id":"19380","type":"CID","arg1_id":"19355","arg2_id":"19336","normalized":[]},{"id":"19381","type":"CID","arg1_id":"19355","arg2_id":"19340","normalized":[]},{"id":"19382","type":"CID","arg1_id":"19355","arg2_id":"19347","normalized":[]},{"id":"19383","type":"CID","arg1_id":"19355","arg2_id":"19363","normalized":[]},{"id":"19384","type":"CID","arg1_id":"19362","arg2_id":"19332","normalized":[]},{"id":"19385","type":"CID","arg1_id":"19362","arg2_id":"19334","normalized":[]},{"id":"19386","type":"CID","arg1_id":"19362","arg2_id":"19336","normalized":[]},{"id":"19387","type":"CID","arg1_id":"19362","arg2_id":"19340","normalized":[]},{"id":"19388","type":"CID","arg1_id":"19362","arg2_id":"19347","normalized":[]},{"id":"19389","type":"CID","arg1_id":"19362","arg2_id":"19363","normalized":[]}]}
{"id":"19390","document_id":"8267029","passages":[{"id":"19391","type":"title","text":["Penicillamine-induced rapidly progressive glomerulonephritis in a patient with rheumatoid arthritis."],"offsets":[[0,100]]},{"id":"19392","type":"abstract","text":["A 67-year-old woman with rheumatoid arthritis presented rapidly progressive glomerulonephritis (RPGN) after 5 months of D-penicillamine (250 mg\/day) treatment. Light microscopy study showed severe glomerulonephritis with crescent formation in 60% of the glomeruli and infiltration of inflammatory cells in the wall of an arteriole. Immunofluorescence revealed scanty granular IgG, IgA and C3 deposits along the capillary walls and mesangium. The patient was treated with steroid pulse, plasmapheresis, cyclophosphamide and antiplatelet agents. A complete recovery of renal function was achieved in a few weeks. This new case of RPGN in the course of D-penicillamine treatment emphasizes the need for frequent monitoring of renal function and evaluation of urinary sediment and proteinuria in these patients. The prompt discontinuation of D-penicillamine and vigorous treatment measures could allow for a good prognosis as in this case."],"offsets":[[101,1036]]}],"entities":[{"id":"19393","type":"Chemical","text":["Penicillamine"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"19394","type":"Disease","text":["glomerulonephritis"],"offsets":[[42,60]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"19395","type":"Disease","text":["rheumatoid arthritis"],"offsets":[[79,99]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"19396","type":"Disease","text":["rheumatoid arthritis"],"offsets":[[126,146]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"19397","type":"Disease","text":["glomerulonephritis"],"offsets":[[177,195]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"19398","type":"Disease","text":["RPGN"],"offsets":[[197,201]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"19399","type":"Chemical","text":["D-penicillamine"],"offsets":[[221,236]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"19400","type":"Disease","text":["glomerulonephritis"],"offsets":[[298,316]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"19401","type":"Chemical","text":["steroid"],"offsets":[[572,579]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"19402","type":"Chemical","text":["cyclophosphamide"],"offsets":[[603,619]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"19403","type":"Chemical","text":["antiplatelet agents"],"offsets":[[624,643]],"normalized":[{"db_name":"MESH","db_id":"D010975"}]},{"id":"19404","type":"Disease","text":["RPGN"],"offsets":[[729,733]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"19405","type":"Chemical","text":["D-penicillamine"],"offsets":[[751,766]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"19406","type":"Disease","text":["proteinuria"],"offsets":[[878,889]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"19407","type":"Chemical","text":["D-penicillamine"],"offsets":[[939,954]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]}],"events":[],"coreferences":[],"relations":[{"id":"19408","type":"CID","arg1_id":"19393","arg2_id":"19394","normalized":[]},{"id":"19409","type":"CID","arg1_id":"19393","arg2_id":"19397","normalized":[]},{"id":"19410","type":"CID","arg1_id":"19393","arg2_id":"19398","normalized":[]},{"id":"19411","type":"CID","arg1_id":"19393","arg2_id":"19400","normalized":[]},{"id":"19412","type":"CID","arg1_id":"19393","arg2_id":"19404","normalized":[]},{"id":"19413","type":"CID","arg1_id":"19399","arg2_id":"19394","normalized":[]},{"id":"19414","type":"CID","arg1_id":"19399","arg2_id":"19397","normalized":[]},{"id":"19415","type":"CID","arg1_id":"19399","arg2_id":"19398","normalized":[]},{"id":"19416","type":"CID","arg1_id":"19399","arg2_id":"19400","normalized":[]},{"id":"19417","type":"CID","arg1_id":"19399","arg2_id":"19404","normalized":[]},{"id":"19418","type":"CID","arg1_id":"19405","arg2_id":"19394","normalized":[]},{"id":"19419","type":"CID","arg1_id":"19405","arg2_id":"19397","normalized":[]},{"id":"19420","type":"CID","arg1_id":"19405","arg2_id":"19398","normalized":[]},{"id":"19421","type":"CID","arg1_id":"19405","arg2_id":"19400","normalized":[]},{"id":"19422","type":"CID","arg1_id":"19405","arg2_id":"19404","normalized":[]},{"id":"19423","type":"CID","arg1_id":"19407","arg2_id":"19394","normalized":[]},{"id":"19424","type":"CID","arg1_id":"19407","arg2_id":"19397","normalized":[]},{"id":"19425","type":"CID","arg1_id":"19407","arg2_id":"19398","normalized":[]},{"id":"19426","type":"CID","arg1_id":"19407","arg2_id":"19400","normalized":[]},{"id":"19427","type":"CID","arg1_id":"19407","arg2_id":"19404","normalized":[]}]}
{"id":"19428","document_id":"2528969","passages":[{"id":"19429","type":"title","text":["Nature, time course and dose dependence of zidovudine-related side effects: results from the Multicenter Canadian Azidothymidine Trial."],"offsets":[[0,135]]},{"id":"19430","type":"abstract","text":["To characterize the nature, time course and dose dependency of zidovudine-related side effects, we undertook a multicenter, prospective, dose-range finding study. Our study group consisted of 74 HIV-positive homosexual men belonging to groups II B, III and IV C2 from the Centers for Disease Control (CDC) classification of HIV disease. Following a 3-week observation period, volunteers were treated with zidovudine 600 mg\/day for 18 weeks, 900 mg\/day for 9 weeks and 1200 mg\/day for 9 weeks, followed by a washout period of 6 weeks after which they were re-started on 1200 mg\/day or the highest tolerated dose at 8-hourly intervals. Subjects were randomly assigned to 4-hourly or 8-hourly regimens within CDC groups while taking 600 and 1200 mg\/day. Clinical and laboratory evaluations were performed at 3-week intervals. Symptomatic adverse effects were present in 96% of subjects, most commonly nausea (64%), fatigue (55%) and headache (49%). These were generally self-limited, reappearing briefly at each dose increment. A decrease in hemoglobin occurred shortly after initiation of therapy. This was not dose dependent and reversed rapidly upon discontinuation of treatment. A red blood cell count decrease, a mean cell volume increase and a granulocyte count decrease developed early in a dose-independent fashion, reverting at least partially during the washout phase. The decrease in reticulocyte count was dose related between 600 and 900 mg\/day with no further change when the dose was escalated to 1200 mg\/day. Bone marrow changes occurred rapidly as demonstrated by megaloblastosis in 95% of 65 specimens at week 18.(ABSTRACT TRUNCATED AT 250 WORDS)"],"offsets":[[136,1797]]}],"entities":[{"id":"19431","type":"Chemical","text":["zidovudine"],"offsets":[[43,53]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"19432","type":"Chemical","text":["Azidothymidine"],"offsets":[[114,128]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"19433","type":"Chemical","text":["zidovudine"],"offsets":[[199,209]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"19434","type":"Disease","text":["HIV disease"],"offsets":[[460,471]],"normalized":[{"db_name":"MESH","db_id":"D015658"}]},{"id":"19435","type":"Chemical","text":["zidovudine"],"offsets":[[541,551]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"19436","type":"Disease","text":["nausea"],"offsets":[[1034,1040]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"19437","type":"Disease","text":["fatigue"],"offsets":[[1048,1055]],"normalized":[{"db_name":"MESH","db_id":"D005221"}]},{"id":"19438","type":"Disease","text":["headache"],"offsets":[[1066,1074]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"19439","type":"Disease","text":["megaloblastosis"],"offsets":[[1714,1729]],"normalized":[]}],"events":[],"coreferences":[],"relations":[{"id":"19440","type":"CID","arg1_id":"19431","arg2_id":"19436","normalized":[]},{"id":"19441","type":"CID","arg1_id":"19432","arg2_id":"19436","normalized":[]},{"id":"19442","type":"CID","arg1_id":"19433","arg2_id":"19436","normalized":[]},{"id":"19443","type":"CID","arg1_id":"19435","arg2_id":"19436","normalized":[]},{"id":"19444","type":"CID","arg1_id":"19431","arg2_id":"19437","normalized":[]},{"id":"19445","type":"CID","arg1_id":"19432","arg2_id":"19437","normalized":[]},{"id":"19446","type":"CID","arg1_id":"19433","arg2_id":"19437","normalized":[]},{"id":"19447","type":"CID","arg1_id":"19435","arg2_id":"19437","normalized":[]},{"id":"19448","type":"CID","arg1_id":"19431","arg2_id":"19438","normalized":[]},{"id":"19449","type":"CID","arg1_id":"19432","arg2_id":"19438","normalized":[]},{"id":"19450","type":"CID","arg1_id":"19433","arg2_id":"19438","normalized":[]},{"id":"19451","type":"CID","arg1_id":"19435","arg2_id":"19438","normalized":[]}]}
{"id":"19452","document_id":"384871","passages":[{"id":"19453","type":"title","text":["Bilateral optic neuropathy due to combined ethambutol and isoniazid treatment."],"offsets":[[0,78]]},{"id":"19454","type":"abstract","text":["The case of a 40-year-old patient who underwent an unsuccessful cadaver kidney transplantation and was treated with ethambutol and isoniazid is reported. A bilateral retrobulbar neuropathy with an unusual central bitemporal hemianopic scotoma was found. Ethambutol was stopped and only small improvement of the visual acuity followed. Isoniazid was discontinued later, followed by a dramatic improvement in the visual acuity. The hazards of optic nerve toxicity due to ethambutol are known. We emphasize the potential danger in the use of ethambutol and isoniazid."],"offsets":[[79,643]]}],"entities":[{"id":"19455","type":"Disease","text":["Bilateral optic neuropathy"],"offsets":[[0,26]],"normalized":[{"db_name":"MESH","db_id":"D009901"}]},{"id":"19456","type":"Chemical","text":["ethambutol"],"offsets":[[43,53]],"normalized":[{"db_name":"MESH","db_id":"D004977"}]},{"id":"19457","type":"Chemical","text":["isoniazid"],"offsets":[[58,67]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]},{"id":"19458","type":"Chemical","text":["ethambutol"],"offsets":[[195,205]],"normalized":[{"db_name":"MESH","db_id":"D004977"}]},{"id":"19459","type":"Chemical","text":["isoniazid"],"offsets":[[210,219]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]},{"id":"19460","type":"Disease","text":["bilateral retrobulbar neuropathy"],"offsets":[[235,267]],"normalized":[{"db_name":"MESH","db_id":"D009901"}]},{"id":"19461","type":"Disease","text":["scotoma"],"offsets":[[314,321]],"normalized":[{"db_name":"MESH","db_id":"D012607"}]},{"id":"19462","type":"Chemical","text":["Ethambutol"],"offsets":[[333,343]],"normalized":[{"db_name":"MESH","db_id":"D004977"}]},{"id":"19463","type":"Chemical","text":["Isoniazid"],"offsets":[[414,423]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]},{"id":"19464","type":"Disease","text":["toxicity"],"offsets":[[532,540]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"19465","type":"Chemical","text":["ethambutol"],"offsets":[[548,558]],"normalized":[{"db_name":"MESH","db_id":"D004977"}]},{"id":"19466","type":"Chemical","text":["ethambutol"],"offsets":[[618,628]],"normalized":[{"db_name":"MESH","db_id":"D004977"}]},{"id":"19467","type":"Chemical","text":["isoniazid"],"offsets":[[633,642]],"normalized":[{"db_name":"MESH","db_id":"D007538"}]}],"events":[],"coreferences":[],"relations":[{"id":"19468","type":"CID","arg1_id":"19457","arg2_id":"19461","normalized":[]},{"id":"19469","type":"CID","arg1_id":"19459","arg2_id":"19461","normalized":[]},{"id":"19470","type":"CID","arg1_id":"19463","arg2_id":"19461","normalized":[]},{"id":"19471","type":"CID","arg1_id":"19467","arg2_id":"19461","normalized":[]},{"id":"19472","type":"CID","arg1_id":"19456","arg2_id":"19455","normalized":[]},{"id":"19473","type":"CID","arg1_id":"19456","arg2_id":"19460","normalized":[]},{"id":"19474","type":"CID","arg1_id":"19458","arg2_id":"19455","normalized":[]},{"id":"19475","type":"CID","arg1_id":"19458","arg2_id":"19460","normalized":[]},{"id":"19476","type":"CID","arg1_id":"19462","arg2_id":"19455","normalized":[]},{"id":"19477","type":"CID","arg1_id":"19462","arg2_id":"19460","normalized":[]},{"id":"19478","type":"CID","arg1_id":"19465","arg2_id":"19455","normalized":[]},{"id":"19479","type":"CID","arg1_id":"19465","arg2_id":"19460","normalized":[]},{"id":"19480","type":"CID","arg1_id":"19466","arg2_id":"19455","normalized":[]},{"id":"19481","type":"CID","arg1_id":"19466","arg2_id":"19460","normalized":[]},{"id":"19482","type":"CID","arg1_id":"19457","arg2_id":"19455","normalized":[]},{"id":"19483","type":"CID","arg1_id":"19457","arg2_id":"19460","normalized":[]},{"id":"19484","type":"CID","arg1_id":"19459","arg2_id":"19455","normalized":[]},{"id":"19485","type":"CID","arg1_id":"19459","arg2_id":"19460","normalized":[]},{"id":"19486","type":"CID","arg1_id":"19463","arg2_id":"19455","normalized":[]},{"id":"19487","type":"CID","arg1_id":"19463","arg2_id":"19460","normalized":[]},{"id":"19488","type":"CID","arg1_id":"19467","arg2_id":"19455","normalized":[]},{"id":"19489","type":"CID","arg1_id":"19467","arg2_id":"19460","normalized":[]},{"id":"19490","type":"CID","arg1_id":"19456","arg2_id":"19461","normalized":[]},{"id":"19491","type":"CID","arg1_id":"19458","arg2_id":"19461","normalized":[]},{"id":"19492","type":"CID","arg1_id":"19462","arg2_id":"19461","normalized":[]},{"id":"19493","type":"CID","arg1_id":"19465","arg2_id":"19461","normalized":[]},{"id":"19494","type":"CID","arg1_id":"19466","arg2_id":"19461","normalized":[]}]}
{"id":"19495","document_id":"133615","passages":[{"id":"19496","type":"title","text":["Progestational agents and blood coagulation. VII. Thromboembolic and other complications of oral contraceptive therapy in relationship to pretreatment levels of blood coagulation factors: summary report of a ten-year study."],"offsets":[[0,223]]},{"id":"19497","type":"abstract","text":["During a ten-year period, 348 women were studied for a total of 5,877 patient months in four separate studies relating oral contraceptives to changes in hematologic parameters. Significant increases in certain factors of the blood coagulation and fibrinolysin systems (factors I,II,VII,VIII,IX, and X and plasminogen) were observed in the treated groups. Severe complications developed in four patients. All four had an abnormal blood coagulation profile, suggesting \"hypercoagulability\" before initiation of therapy. Some of these findings represented the most extreme abnormalities seen in the entire group of patients; some increased further during therapy. One of these patients developed a myocardial infarction before receiving any medication, shortly after the base-line values were obtained. One patient developed retinopathy 19 months after she began therapy, and another developed thrombophlebitis after 27 months of therapy. The fourth patient developed thrombophlebitis 14 days after initiation of contraceptive therapy. All four patients were of the A or AB blood group. Previous studies suggested the possiblility of increased propensity for thromboembolic episodes in patients possessing the A antigen. It appears from these data that hematologic work-ups may be useful in women who are about to start long-term oral contraceptive therapy."],"offsets":[[224,1578]]}],"entities":[{"id":"19498","type":"Disease","text":["blood coagulation"],"offsets":[[26,43]],"normalized":[{"db_name":"MESH","db_id":"D001778"}]},{"id":"19499","type":"Disease","text":["Thromboembolic"],"offsets":[[50,64]],"normalized":[{"db_name":"MESH","db_id":"D013923"}]},{"id":"19500","type":"Chemical","text":["oral contraceptive"],"offsets":[[92,110]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"19501","type":"Disease","text":["blood coagulation"],"offsets":[[161,178]],"normalized":[{"db_name":"MESH","db_id":"D001778"}]},{"id":"19502","type":"Chemical","text":["oral contraceptives"],"offsets":[[343,362]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]},{"id":"19503","type":"Disease","text":["blood coagulation"],"offsets":[[449,466]],"normalized":[{"db_name":"MESH","db_id":"D001778"}]},{"id":"19504","type":"Disease","text":["blood coagulation"],"offsets":[[653,670]],"normalized":[{"db_name":"MESH","db_id":"D001778"}]},{"id":"19505","type":"Disease","text":["hypercoagulability"],"offsets":[[692,710]],"normalized":[{"db_name":"MESH","db_id":"D019851"}]},{"id":"19506","type":"Disease","text":["myocardial infarction"],"offsets":[[919,940]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"19507","type":"Disease","text":["retinopathy"],"offsets":[[1046,1057]],"normalized":[{"db_name":"MESH","db_id":"D012164"}]},{"id":"19508","type":"Disease","text":["thrombophlebitis"],"offsets":[[1115,1131]],"normalized":[{"db_name":"MESH","db_id":"D013924"}]},{"id":"19509","type":"Disease","text":["thrombophlebitis"],"offsets":[[1189,1205]],"normalized":[{"db_name":"MESH","db_id":"D013924"}]},{"id":"19510","type":"Disease","text":["thromboembolic episodes"],"offsets":[[1380,1403]],"normalized":[{"db_name":"MESH","db_id":"D013923"}]},{"id":"19511","type":"Chemical","text":["oral contraceptive"],"offsets":[[1551,1569]],"normalized":[{"db_name":"MESH","db_id":"D003276"}]}],"events":[],"coreferences":[],"relations":[{"id":"19512","type":"CID","arg1_id":"19500","arg2_id":"19498","normalized":[]},{"id":"19513","type":"CID","arg1_id":"19500","arg2_id":"19501","normalized":[]},{"id":"19514","type":"CID","arg1_id":"19500","arg2_id":"19503","normalized":[]},{"id":"19515","type":"CID","arg1_id":"19500","arg2_id":"19504","normalized":[]},{"id":"19516","type":"CID","arg1_id":"19502","arg2_id":"19498","normalized":[]},{"id":"19517","type":"CID","arg1_id":"19502","arg2_id":"19501","normalized":[]},{"id":"19518","type":"CID","arg1_id":"19502","arg2_id":"19503","normalized":[]},{"id":"19519","type":"CID","arg1_id":"19502","arg2_id":"19504","normalized":[]},{"id":"19520","type":"CID","arg1_id":"19511","arg2_id":"19498","normalized":[]},{"id":"19521","type":"CID","arg1_id":"19511","arg2_id":"19501","normalized":[]},{"id":"19522","type":"CID","arg1_id":"19511","arg2_id":"19503","normalized":[]},{"id":"19523","type":"CID","arg1_id":"19511","arg2_id":"19504","normalized":[]},{"id":"19524","type":"CID","arg1_id":"19500","arg2_id":"19507","normalized":[]},{"id":"19525","type":"CID","arg1_id":"19502","arg2_id":"19507","normalized":[]},{"id":"19526","type":"CID","arg1_id":"19511","arg2_id":"19507","normalized":[]},{"id":"19527","type":"CID","arg1_id":"19500","arg2_id":"19508","normalized":[]},{"id":"19528","type":"CID","arg1_id":"19500","arg2_id":"19509","normalized":[]},{"id":"19529","type":"CID","arg1_id":"19502","arg2_id":"19508","normalized":[]},{"id":"19530","type":"CID","arg1_id":"19502","arg2_id":"19509","normalized":[]},{"id":"19531","type":"CID","arg1_id":"19511","arg2_id":"19508","normalized":[]},{"id":"19532","type":"CID","arg1_id":"19511","arg2_id":"19509","normalized":[]},{"id":"19533","type":"CID","arg1_id":"19500","arg2_id":"19506","normalized":[]},{"id":"19534","type":"CID","arg1_id":"19502","arg2_id":"19506","normalized":[]},{"id":"19535","type":"CID","arg1_id":"19511","arg2_id":"19506","normalized":[]}]}
{"id":"19536","document_id":"17263743","passages":[{"id":"19537","type":"title","text":["Cardiac arrest in a child with cerebral palsy undergoing sevoflurane induction of anesthesia after preoperative clonidine."],"offsets":[[0,122]]},{"id":"19538","type":"abstract","text":["Clonidine is a frequently administered alpha2-adrenergic agonist which can decrease heart rate and blood pressure. We present a case of a 5-year-old child with cerebral palsy and seizure disorder, receiving clonidine for restlessness, who presented for placement of a baclofen pump. Without the knowledge of the medical personnel, the patient's mother administered three doses of clonidine during the evening before and morning of surgery to reduce anxiety. During induction of anesthesia, the patient developed bradycardia and hypotension requiring cardiac resuscitation. There are no previous reports of clonidine-associated cardiac arrest in a child undergoing induction of anesthesia."],"offsets":[[123,811]]}],"entities":[{"id":"19539","type":"Disease","text":["Cardiac arrest"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"19540","type":"Disease","text":["cerebral palsy"],"offsets":[[31,45]],"normalized":[{"db_name":"MESH","db_id":"D002547"}]},{"id":"19541","type":"Chemical","text":["sevoflurane"],"offsets":[[57,68]],"normalized":[{"db_name":"MESH","db_id":"C009250"}]},{"id":"19542","type":"Chemical","text":["clonidine"],"offsets":[[112,121]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"19543","type":"Chemical","text":["Clonidine"],"offsets":[[123,132]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"19544","type":"Disease","text":["cerebral palsy"],"offsets":[[283,297]],"normalized":[{"db_name":"MESH","db_id":"D002547"}]},{"id":"19545","type":"Disease","text":["seizure disorder"],"offsets":[[302,318]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"19546","type":"Chemical","text":["clonidine"],"offsets":[[330,339]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"19547","type":"Disease","text":["restlessness"],"offsets":[[344,356]],"normalized":[{"db_name":"MESH","db_id":"D011595"}]},{"id":"19548","type":"Chemical","text":["baclofen"],"offsets":[[391,399]],"normalized":[{"db_name":"MESH","db_id":"D001418"}]},{"id":"19549","type":"Chemical","text":["clonidine"],"offsets":[[503,512]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"19550","type":"Disease","text":["anxiety"],"offsets":[[572,579]],"normalized":[{"db_name":"MESH","db_id":"D001008"}]},{"id":"19551","type":"Disease","text":["bradycardia"],"offsets":[[635,646]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"19552","type":"Disease","text":["hypotension"],"offsets":[[651,662]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"19553","type":"Chemical","text":["clonidine"],"offsets":[[729,738]],"normalized":[{"db_name":"MESH","db_id":"D003000"}]},{"id":"19554","type":"Disease","text":["cardiac arrest"],"offsets":[[750,764]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]}],"events":[],"coreferences":[],"relations":[{"id":"19555","type":"CID","arg1_id":"19542","arg2_id":"19552","normalized":[]},{"id":"19556","type":"CID","arg1_id":"19543","arg2_id":"19552","normalized":[]},{"id":"19557","type":"CID","arg1_id":"19546","arg2_id":"19552","normalized":[]},{"id":"19558","type":"CID","arg1_id":"19549","arg2_id":"19552","normalized":[]},{"id":"19559","type":"CID","arg1_id":"19553","arg2_id":"19552","normalized":[]},{"id":"19560","type":"CID","arg1_id":"19542","arg2_id":"19551","normalized":[]},{"id":"19561","type":"CID","arg1_id":"19543","arg2_id":"19551","normalized":[]},{"id":"19562","type":"CID","arg1_id":"19546","arg2_id":"19551","normalized":[]},{"id":"19563","type":"CID","arg1_id":"19549","arg2_id":"19551","normalized":[]},{"id":"19564","type":"CID","arg1_id":"19553","arg2_id":"19551","normalized":[]},{"id":"19565","type":"CID","arg1_id":"19542","arg2_id":"19539","normalized":[]},{"id":"19566","type":"CID","arg1_id":"19542","arg2_id":"19554","normalized":[]},{"id":"19567","type":"CID","arg1_id":"19543","arg2_id":"19539","normalized":[]},{"id":"19568","type":"CID","arg1_id":"19543","arg2_id":"19554","normalized":[]},{"id":"19569","type":"CID","arg1_id":"19546","arg2_id":"19539","normalized":[]},{"id":"19570","type":"CID","arg1_id":"19546","arg2_id":"19554","normalized":[]},{"id":"19571","type":"CID","arg1_id":"19549","arg2_id":"19539","normalized":[]},{"id":"19572","type":"CID","arg1_id":"19549","arg2_id":"19554","normalized":[]},{"id":"19573","type":"CID","arg1_id":"19553","arg2_id":"19539","normalized":[]},{"id":"19574","type":"CID","arg1_id":"19553","arg2_id":"19554","normalized":[]}]}
{"id":"19575","document_id":"17241657","passages":[{"id":"19576","type":"title","text":["Effects of UMB24 and (+\/-)-SM 21, putative sigma2-preferring antagonists, on behavioral toxic and stimulant effects of cocaine in mice."],"offsets":[[0,135]]},{"id":"19577","type":"abstract","text":["Earlier studies have demonstrated that antagonism of sigma1 receptors attenuates the convulsive, lethal, locomotor stimulatory and rewarding actions of cocaine in mice. In contrast, the contribution of sigma2 receptors is unclear because experimental tools to selectively target this subtype are unavailable. To begin addressing this need, we characterized UMB24 (1-(2-phenethyl)-4-(2-pyridyl)-piperazine) and (+\/-)-SM 21 (3alpha-tropanyl-2-(4-chorophenoxy)butyrate) in receptor binding and behavioral studies. Receptor binding studies confirmed that UMB24 and (+\/-)-SM 21 display preferential affinity for sigma2 over sigma1 receptors. In behavioral studies, pretreatment of Swiss Webster mice with UMB24 or (+\/-)-SM 21 significantly attenuated cocaine-induced convulsions and locomotor activity, but not lethality. When administered alone, (+\/-)-SM 21 produced no significant effects compared to control injections of saline, but UMB24 had locomotor depressant actions. Together, the data suggest that sigma2 receptor antagonists have the potential to attenuate some of the behavioral effects of cocaine, and further development of more selective, high affinity ligands are warranted."],"offsets":[[136,1322]]}],"entities":[{"id":"19578","type":"Chemical","text":["UMB24"],"offsets":[[11,16]],"normalized":[{"db_name":"MESH","db_id":"C519696"}]},{"id":"19579","type":"Chemical","text":["SM 21"],"offsets":[[27,32]],"normalized":[{"db_name":"MESH","db_id":"C107044"}]},{"id":"19580","type":"Chemical","text":["cocaine"],"offsets":[[119,126]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"19581","type":"Disease","text":["convulsive"],"offsets":[[221,231]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"19582","type":"Chemical","text":["cocaine"],"offsets":[[288,295]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"19583","type":"Chemical","text":["UMB24"],"offsets":[[493,498]],"normalized":[{"db_name":"MESH","db_id":"C519696"}]},{"id":"19584","type":"Chemical","text":["1-(2-phenethyl)-4-(2-pyridyl)-piperazine"],"offsets":[[500,540]],"normalized":[{"db_name":"MESH","db_id":"C519696"}]},{"id":"19585","type":"Chemical","text":["SM 21"],"offsets":[[552,557]],"normalized":[{"db_name":"MESH","db_id":"C107044"}]},{"id":"19586","type":"Chemical","text":["3alpha-tropanyl-2-(4-chorophenoxy)butyrate"],"offsets":[[559,601]],"normalized":[{"db_name":"MESH","db_id":"C107044"}]},{"id":"19587","type":"Chemical","text":["UMB24"],"offsets":[[687,692]],"normalized":[{"db_name":"MESH","db_id":"C519696"}]},{"id":"19588","type":"Chemical","text":["SM 21"],"offsets":[[703,708]],"normalized":[{"db_name":"MESH","db_id":"C107044"}]},{"id":"19589","type":"Chemical","text":["UMB24"],"offsets":[[836,841]],"normalized":[{"db_name":"MESH","db_id":"C519696"}]},{"id":"19590","type":"Chemical","text":["SM 21"],"offsets":[[851,856]],"normalized":[{"db_name":"MESH","db_id":"C107044"}]},{"id":"19591","type":"Chemical","text":["cocaine"],"offsets":[[882,889]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"19592","type":"Disease","text":["convulsions"],"offsets":[[898,909]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"19593","type":"Chemical","text":["SM 21"],"offsets":[[984,989]],"normalized":[{"db_name":"MESH","db_id":"C107044"}]},{"id":"19594","type":"Chemical","text":["UMB24"],"offsets":[[1068,1073]],"normalized":[{"db_name":"MESH","db_id":"C519696"}]},{"id":"19595","type":"Chemical","text":["cocaine"],"offsets":[[1234,1241]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]}],"events":[],"coreferences":[],"relations":[{"id":"19596","type":"CID","arg1_id":"19580","arg2_id":"19581","normalized":[]},{"id":"19597","type":"CID","arg1_id":"19580","arg2_id":"19592","normalized":[]},{"id":"19598","type":"CID","arg1_id":"19582","arg2_id":"19581","normalized":[]},{"id":"19599","type":"CID","arg1_id":"19582","arg2_id":"19592","normalized":[]},{"id":"19600","type":"CID","arg1_id":"19591","arg2_id":"19581","normalized":[]},{"id":"19601","type":"CID","arg1_id":"19591","arg2_id":"19592","normalized":[]},{"id":"19602","type":"CID","arg1_id":"19595","arg2_id":"19581","normalized":[]},{"id":"19603","type":"CID","arg1_id":"19595","arg2_id":"19592","normalized":[]}]}
{"id":"19604","document_id":"14982270","passages":[{"id":"19605","type":"title","text":["Methimazole-induced cholestatic jaundice."],"offsets":[[0,41]]},{"id":"19606","type":"abstract","text":["Methimazole is a widely used and generally well-tolerated antithyroid agent. A 43-year-old woman had severe jaundice and itching 1 month after receiving methimazole (10 mg tid) and propranolol (20 mg tid) for treatment of hyperthyroidism. The patient continued treatment for another 4 days after the appearance of jaundice until she finished both medications. When seen at the emergency department 2 weeks later, she still had severe icterus, pruritus, and hyperbilirubinemia, formed mainly of the conjugated fraction. Methimazole-induced cholestasis was diagnosed, and propranolol therapy was resumed. Over the following 9 days, the symptoms improved and plasma bilirubin levels were normal after 12 weeks without methimazole. In rare cases within the first few weeks of therapy, this drug can cause severe and reversible cholestatic jaundice. Physicians and patients should be aware of this adverse effect so that, upon occurrence, they can discontinue methimazole therapy and avoid unnecessary invasive procedures."],"offsets":[[42,1059]]}],"entities":[{"id":"19607","type":"Chemical","text":["Methimazole"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D008713"}]},{"id":"19608","type":"Disease","text":["cholestatic jaundice"],"offsets":[[20,40]],"normalized":[{"db_name":"MESH","db_id":"D041781"}]},{"id":"19609","type":"Chemical","text":["Methimazole"],"offsets":[[42,53]],"normalized":[{"db_name":"MESH","db_id":"D008713"}]},{"id":"19610","type":"Disease","text":["jaundice"],"offsets":[[150,158]],"normalized":[{"db_name":"MESH","db_id":"D007565"}]},{"id":"19611","type":"Disease","text":["itching"],"offsets":[[163,170]],"normalized":[{"db_name":"MESH","db_id":"D011537"}]},{"id":"19612","type":"Chemical","text":["methimazole"],"offsets":[[195,206]],"normalized":[{"db_name":"MESH","db_id":"D008713"}]},{"id":"19613","type":"Chemical","text":["propranolol"],"offsets":[[223,234]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"19614","type":"Disease","text":["hyperthyroidism"],"offsets":[[264,279]],"normalized":[{"db_name":"MESH","db_id":"D006980"}]},{"id":"19615","type":"Disease","text":["jaundice"],"offsets":[[356,364]],"normalized":[{"db_name":"MESH","db_id":"D007565"}]},{"id":"19616","type":"Disease","text":["icterus"],"offsets":[[476,483]],"normalized":[{"db_name":"MESH","db_id":"D007565"}]},{"id":"19617","type":"Disease","text":["pruritus"],"offsets":[[485,493]],"normalized":[{"db_name":"MESH","db_id":"D011537"}]},{"id":"19618","type":"Disease","text":["hyperbilirubinemia"],"offsets":[[499,517]],"normalized":[{"db_name":"MESH","db_id":"D006932"}]},{"id":"19619","type":"Chemical","text":["Methimazole"],"offsets":[[561,572]],"normalized":[{"db_name":"MESH","db_id":"D008713"}]},{"id":"19620","type":"Disease","text":["cholestasis"],"offsets":[[581,592]],"normalized":[{"db_name":"MESH","db_id":"D002779"}]},{"id":"19621","type":"Chemical","text":["propranolol"],"offsets":[[612,623]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"19622","type":"Chemical","text":["bilirubin"],"offsets":[[705,714]],"normalized":[{"db_name":"MESH","db_id":"D001663"}]},{"id":"19623","type":"Chemical","text":["methimazole"],"offsets":[[757,768]],"normalized":[{"db_name":"MESH","db_id":"D008713"}]},{"id":"19624","type":"Disease","text":["cholestatic 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{"id":"19656","document_id":"12911170","passages":[{"id":"19657","type":"title","text":["Ciprofloxacin-induced acute interstitial nephritis and autoimmune hemolytic anemia."],"offsets":[[0,83]]},{"id":"19658","type":"abstract","text":["Ciprofloxacin has been associated with several side effects including interstitial nephritis and hemolytic anemia. The combination of both side effects is extremely rare. In this report, we describe a case of ciprofloxacin-induced interstitial nephritis and autoimmune hemolytic anemia. Hemolytic anemia improved after stopping the drug and initiation of steroid therapy. Unfortunately, acute interstitial nephritis was irreversible and the patient developed end-stage renal disease."],"offsets":[[84,567]]}],"entities":[{"id":"19659","type":"Chemical","text":["Ciprofloxacin"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D002939"}]},{"id":"19660","type":"Disease","text":["interstitial nephritis"],"offsets":[[28,50]],"normalized":[{"db_name":"MESH","db_id":"D009395"}]},{"id":"19661","type":"Disease","text":["autoimmune hemolytic anemia"],"offsets":[[55,82]],"normalized":[{"db_name":"MESH","db_id":"D000744"}]},{"id":"19662","type":"Chemical","text":["Ciprofloxacin"],"offsets":[[84,97]],"normalized":[{"db_name":"MESH","db_id":"D002939"}]},{"id":"19663","type":"Disease","text":["interstitial nephritis"],"offsets":[[154,176]],"normalized":[{"db_name":"MESH","db_id":"D009395"}]},{"id":"19664","type":"Disease","text":["hemolytic anemia"],"offsets":[[181,197]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"19665","type":"Chemical","text":["ciprofloxacin"],"offsets":[[293,306]],"normalized":[{"db_name":"MESH","db_id":"D002939"}]},{"id":"19666","type":"Disease","text":["interstitial nephritis"],"offsets":[[315,337]],"normalized":[{"db_name":"MESH","db_id":"D009395"}]},{"id":"19667","type":"Disease","text":["autoimmune hemolytic anemia"],"offsets":[[342,369]],"normalized":[{"db_name":"MESH","db_id":"D000744"}]},{"id":"19668","type":"Disease","text":["Hemolytic anemia"],"offsets":[[371,387]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"19669","type":"Chemical","text":["steroid"],"offsets":[[439,446]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"19670","type":"Disease","text":["interstitial nephritis"],"offsets":[[477,499]],"normalized":[{"db_name":"MESH","db_id":"D009395"}]},{"id":"19671","type":"Disease","text":["end-stage renal disease"],"offsets":[[543,566]],"normalized":[{"db_name":"MESH","db_id":"D007676"}]}],"events":[],"coreferences":[],"relations":[{"id":"19672","type":"CID","arg1_id":"19659","arg2_id":"19664","normalized":[]},{"id":"19673","type":"CID","arg1_id":"19659","arg2_id":"19668","normalized":[]},{"id":"19674","type":"CID","arg1_id":"19662","arg2_id":"19664","normalized":[]},{"id":"19675","type":"CID","arg1_id":"19662","arg2_id":"19668","normalized":[]},{"id":"19676","type":"CID","arg1_id":"19665","arg2_id":"19664","normalized":[]},{"id":"19677","type":"CID","arg1_id":"19665","arg2_id":"19668","normalized":[]},{"id":"19678","type":"CID","arg1_id":"19659","arg2_id":"19671","normalized":[]},{"id":"19679","type":"CID","arg1_id":"19662","arg2_id":"19671","normalized":[]},{"id":"19680","type":"CID","arg1_id":"19665","arg2_id":"19671","normalized":[]},{"id":"19681","type":"CID","arg1_id":"19659","arg2_id":"19660","normalized":[]},{"id":"19682","type":"CID","arg1_id":"19659","arg2_id":"19663","normalized":[]},{"id":"19683","type":"CID","arg1_id":"19659","arg2_id":"19666","normalized":[]},{"id":"19684","type":"CID","arg1_id":"19659","arg2_id":"19670","normalized":[]},{"id":"19685","type":"CID","arg1_id":"19662","arg2_id":"19660","normalized":[]},{"id":"19686","type":"CID","arg1_id":"19662","arg2_id":"19663","normalized":[]},{"id":"19687","type":"CID","arg1_id":"19662","arg2_id":"19666","normalized":[]},{"id":"19688","type":"CID","arg1_id":"19662","arg2_id":"19670","normalized":[]},{"id":"19689","type":"CID","arg1_id":"19665","arg2_id":"19660","normalized":[]},{"id":"19690","type":"CID","arg1_id":"19665","arg2_id":"19663","normalized":[]},{"id":"19691","type":"CID","arg1_id":"19665","arg2_id":"19666","normalized":[]},{"id":"19692","type":"CID","arg1_id":"19665","arg2_id":"19670","normalized":[]}]}
{"id":"19693","document_id":"11195262","passages":[{"id":"19694","type":"title","text":["Contribution of sodium valproate to the syndrome of inappropriate secretion of antidiuretic hormone."],"offsets":[[0,100]]},{"id":"19695","type":"abstract","text":["We report the case of a 62-year-old man who was administered sodium valproate (VPA) and who subsequently developed the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). He had been taking VPA for treatment of idiopathic generalized tonic-clonic convulsions since he was 56 years old. After substituting VPA with zonisamide, the serum sodium level returned to normal. We consider this episode of SIADH to be the result of a combination of factors including a weakness of the central nervous system and the long-term administration of VPA."],"offsets":[[101,657]]}],"entities":[{"id":"19696","type":"Chemical","text":["sodium valproate"],"offsets":[[16,32]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"19697","type":"Disease","text":["syndrome of inappropriate secretion of antidiuretic hormone"],"offsets":[[40,99]],"normalized":[{"db_name":"MESH","db_id":"D007177"}]},{"id":"19698","type":"Chemical","text":["sodium valproate"],"offsets":[[162,178]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"19699","type":"Chemical","text":["VPA"],"offsets":[[180,183]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"19700","type":"Disease","text":["syndrome of inappropriate secretion of antidiuretic hormone"],"offsets":[[220,279]],"normalized":[{"db_name":"MESH","db_id":"D007177"}]},{"id":"19701","type":"Disease","text":["SIADH"],"offsets":[[281,286]],"normalized":[{"db_name":"MESH","db_id":"D007177"}]},{"id":"19702","type":"Chemical","text":["VPA"],"offsets":[[308,311]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"19703","type":"Disease","text":["tonic-clonic convulsions"],"offsets":[[352,376]],"normalized":[{"db_name":"MESH","db_id":"D004830"}]},{"id":"19704","type":"Chemical","text":["VPA"],"offsets":[[423,426]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]},{"id":"19705","type":"Chemical","text":["zonisamide"],"offsets":[[432,442]],"normalized":[{"db_name":"MESH","db_id":"C022189"}]},{"id":"19706","type":"Chemical","text":["sodium"],"offsets":[[454,460]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"19707","type":"Disease","text":["SIADH"],"offsets":[[515,520]],"normalized":[{"db_name":"MESH","db_id":"D007177"}]},{"id":"19708","type":"Disease","text":["weakness of the central nervous system"],"offsets":[[578,616]],"normalized":[{"db_name":"MESH","db_id":"D002493"}]},{"id":"19709","type":"Chemical","text":["VPA"],"offsets":[[653,656]],"normalized":[{"db_name":"MESH","db_id":"D014635"}]}],"events":[],"coreferences":[],"relations":[{"id":"19710","type":"CID","arg1_id":"19696","arg2_id":"19697","normalized":[]},{"id":"19711","type":"CID","arg1_id":"19696","arg2_id":"19700","normalized":[]},{"id":"19712","type":"CID","arg1_id":"19696","arg2_id":"19701","normalized":[]},{"id":"19713","type":"CID","arg1_id":"19696","arg2_id":"19707","normalized":[]},{"id":"19714","type":"CID","arg1_id":"19698","arg2_id":"19697","normalized":[]},{"id":"19715","type":"CID","arg1_id":"19698","arg2_id":"19700","normalized":[]},{"id":"19716","type":"CID","arg1_id":"19698","arg2_id":"19701","normalized":[]},{"id":"19717","type":"CID","arg1_id":"19698","arg2_id":"19707","normalized":[]},{"id":"19718","type":"CID","arg1_id":"19699","arg2_id":"19697","normalized":[]},{"id":"19719","type":"CID","arg1_id":"19699","arg2_id":"19700","normalized":[]},{"id":"19720","type":"CID","arg1_id":"19699","arg2_id":"19701","normalized":[]},{"id":"19721","type":"CID","arg1_id":"19699","arg2_id":"19707","normalized":[]},{"id":"19722","type":"CID","arg1_id":"19702","arg2_id":"19697","normalized":[]},{"id":"19723","type":"CID","arg1_id":"19702","arg2_id":"19700","normalized":[]},{"id":"19724","type":"CID","arg1_id":"19702","arg2_id":"19701","normalized":[]},{"id":"19725","type":"CID","arg1_id":"19702","arg2_id":"19707","normalized":[]},{"id":"19726","type":"CID","arg1_id":"19704","arg2_id":"19697","normalized":[]},{"id":"19727","type":"CID","arg1_id":"19704","arg2_id":"19700","normalized":[]},{"id":"19728","type":"CID","arg1_id":"19704","arg2_id":"19701","normalized":[]},{"id":"19729","type":"CID","arg1_id":"19704","arg2_id":"19707","normalized":[]},{"id":"19730","type":"CID","arg1_id":"19709","arg2_id":"19697","normalized":[]},{"id":"19731","type":"CID","arg1_id":"19709","arg2_id":"19700","normalized":[]},{"id":"19732","type":"CID","arg1_id":"19709","arg2_id":"19701","normalized":[]},{"id":"19733","type":"CID","arg1_id":"19709","arg2_id":"19707","normalized":[]}]}
{"id":"19734","document_id":"10728962","passages":[{"id":"19735","type":"title","text":["Vasopressin in the treatment of milrinone-induced hypotension in severe heart failure."],"offsets":[[0,86]]},{"id":"19736","type":"abstract","text":["The use of phosphodiesterase inhibitors such as milrinone in the treatment of severe heart failure is frequently restricted because they cause vasodilation and hypotension. In patients with decompensated heart failure with hypotension after treatment with milrinone, low doses of vasopressin restored blood pressure without inhibiting the inotropic effect of milrinone."],"offsets":[[87,456]]}],"entities":[{"id":"19737","type":"Chemical","text":["Vasopressin"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D014667"}]},{"id":"19738","type":"Chemical","text":["milrinone"],"offsets":[[32,41]],"normalized":[{"db_name":"MESH","db_id":"D020105"}]},{"id":"19739","type":"Disease","text":["hypotension"],"offsets":[[50,61]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"19740","type":"Disease","text":["heart failure"],"offsets":[[72,85]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"19741","type":"Chemical","text":["milrinone"],"offsets":[[135,144]],"normalized":[{"db_name":"MESH","db_id":"D020105"}]},{"id":"19742","type":"Disease","text":["heart failure"],"offsets":[[172,185]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"19743","type":"Disease","text":["hypotension"],"offsets":[[247,258]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"19744","type":"Disease","text":["heart failure"],"offsets":[[291,304]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"19745","type":"Disease","text":["hypotension"],"offsets":[[310,321]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"19746","type":"Chemical","text":["milrinone"],"offsets":[[343,352]],"normalized":[{"db_name":"MESH","db_id":"D020105"}]},{"id":"19747","type":"Chemical","text":["vasopressin"],"offsets":[[367,378]],"normalized":[{"db_name":"MESH","db_id":"D014667"}]},{"id":"19748","type":"Chemical","text":["milrinone"],"offsets":[[446,455]],"normalized":[{"db_name":"MESH","db_id":"D020105"}]}],"events":[],"coreferences":[],"relations":[{"id":"19749","type":"CID","arg1_id":"19737","arg2_id":"19739","normalized":[]},{"id":"19750","type":"CID","arg1_id":"19737","arg2_id":"19743","normalized":[]},{"id":"19751","type":"CID","arg1_id":"19737","arg2_id":"19745","normalized":[]},{"id":"19752","type":"CID","arg1_id":"19747","arg2_id":"19739","normalized":[]},{"id":"19753","type":"CID","arg1_id":"19747","arg2_id":"19743","normalized":[]},{"id":"19754","type":"CID","arg1_id":"19747","arg2_id":"19745","normalized":[]},{"id":"19755","type":"CID","arg1_id":"19738","arg2_id":"19739","normalized":[]},{"id":"19756","type":"CID","arg1_id":"19738","arg2_id":"19743","normalized":[]},{"id":"19757","type":"CID","arg1_id":"19738","arg2_id":"19745","normalized":[]},{"id":"19758","type":"CID","arg1_id":"19741","arg2_id":"19739","normalized":[]},{"id":"19759","type":"CID","arg1_id":"19741","arg2_id":"19743","normalized":[]},{"id":"19760","type":"CID","arg1_id":"19741","arg2_id":"19745","normalized":[]},{"id":"19761","type":"CID","arg1_id":"19746","arg2_id":"19739","normalized":[]},{"id":"19762","type":"CID","arg1_id":"19746","arg2_id":"19743","normalized":[]},{"id":"19763","type":"CID","arg1_id":"19746","arg2_id":"19745","normalized":[]},{"id":"19764","type":"CID","arg1_id":"19748","arg2_id":"19739","normalized":[]},{"id":"19765","type":"CID","arg1_id":"19748","arg2_id":"19743","normalized":[]},{"id":"19766","type":"CID","arg1_id":"19748","arg2_id":"19745","normalized":[]}]}
{"id":"19767","document_id":"7647582","passages":[{"id":"19768","type":"title","text":["Halogenated anesthetics form liver adducts and antigens that cross-react with halothane-induced antibodies."],"offsets":[[0,107]]},{"id":"19769","type":"abstract","text":["Two halogenated anesthetics, enflurane and isoflurane, have been associated with an allergic-type hepatic injury both alone and following previous exposure to halothane. Halothane hepatitis appears to involve an aberrant immune response. An antibody response to a protein-bound biotransformation product (trifluoroacetyl adduct) has been detected on halothane hepatitis patients. This study was performed to determine cross-reactivity between enflurane and isoflurane with the hypersensitivity induced by halothane. The subcellular and lobular production of hepatic neoantigens recognized by halothane-induced antibodies following enflurane and isoflurane, and the biochemical nature of these neoantigens was investigated in two animal models. Enflurane administration resulted in neoantigens detected in both the microsomal and cytosolic fraction of liver homogenates and in the centrilobular region of the liver. In the same liver, biochemical analysis detected fluorinated liver adducts that were up to 20-fold greater in guinea pigs than in rats. This supports and extends previous evidence for a mechanism by which enflurane and\/or isoflurane could produce a hypersensitivity condition similar to that of halothane hepatitis either alone or subsequent to halothane administration. The guinea pig would appear to be a useful model for further investigations of the immunological response to these antigens."],"offsets":[[108,1518]]}],"entities":[{"id":"19770","type":"Chemical","text":["halothane"],"offsets":[[78,87]],"normalized":[{"db_name":"MESH","db_id":"D006221"}]},{"id":"19771","type":"Chemical","text":["enflurane"],"offsets":[[137,146]],"normalized":[{"db_name":"MESH","db_id":"D004737"}]},{"id":"19772","type":"Chemical","text":["isoflurane"],"offsets":[[151,161]],"normalized":[{"db_name":"MESH","db_id":"D007530"}]},{"id":"19773","type":"Disease","text":["hepatic 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{"id":"19862","document_id":"4090988","passages":[{"id":"19863","type":"title","text":["Induction by paracetamol of bladder and liver tumours in the rat. Effects on hepatocyte fine structure."],"offsets":[[0,103]]},{"id":"19864","type":"abstract","text":["Groups of male and female inbred Leeds strain rats were fed diets containing either 0.5% or 1.0% paracetamol by weight for up to 18 months. At the 1.0% dosage level, 20% of rats of both sexes developed neoplastic nodules of the liver, a statistically significant incidence. These rats also showed gross enlargement of their livers and an increase in foci of cellular alteration, the latter also being observed in the low dosage male rats. Papillomas of the transitional epithelium of the bladder developed in all paracetamol-treated groups, and three rats bore bladder carcinomas. However, significant yields of bladder tumours were only obtained from low dosage females and high dosage males. Additionally, 20 to 25% of paracetamol-treated rats developed hyperplasia of the bladder epithelium, which was not coincident with the presence of bladder calculi. A low yield of tumours at various other sites also arose following paracetamol feeding. An electron microscope study of the livers of paracetamol-treated rats revealed ultrastructural changes in the hepatocytes that resemble those that result from exposure to a variety of known hepatocarcinogens."],"offsets":[[104,1259]]}],"entities":[{"id":"19865","type":"Chemical","text":["paracetamol"],"offsets":[[13,24]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"19866","type":"Disease","text":["bladder and liver tumours"],"offsets":[[28,53]],"normalized":[{"db_name":"MESH","db_id":"D001749"},{"db_name":"MESH","db_id":"D008113"}]},{"id":"19867","type":"Disease","text":["bladder","tumours"],"offsets":[[28,35],[46,53]],"normalized":[{"db_name":"MESH","db_id":"D001749"}]},{"id":"19868","type":"Disease","text":["liver 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{"id":"19929","document_id":"4038130","passages":[{"id":"19930","type":"title","text":["Rat extraocular muscle regeneration. Repair of local anesthetic-induced damage."],"offsets":[[0,79]]},{"id":"19931","type":"abstract","text":["Local anesthetics that are commonly used in ophthalmic surgery (0.75% bupivacaine hydrochloride, 2.0% mepivacaine hydrochloride, and 2.0% lidocaine hydrochloride plus 1:100,000 epinephrine) were injected into the retrobulbar area of rat eyes. Controls were injected with physiological saline. All three anesthetics produced massive degeneration of the extraocular muscles. Muscle degeneration is followed by regeneration of the damaged muscle fibers. In addition to muscle damage, severe damage was also seen in harderian glands, especially after exposure to mepivacaine and lidocaine plus epinephrine. With these findings in rats, it is hypothesized that the temporary diplopia sometimes seen in patients after ophthalmic surgery might be due to anesthetic-induced damage to the extraocular muscles."],"offsets":[[80,880]]}],"entities":[{"id":"19932","type":"Chemical","text":["bupivacaine hydrochloride"],"offsets":[[150,175]],"normalized":[{"db_name":"MESH","db_id":"D002045"}]},{"id":"19933","type":"Chemical","text":["mepivacaine hydrochloride"],"offsets":[[182,207]],"normalized":[{"db_name":"MESH","db_id":"D008619"}]},{"id":"19934","type":"Chemical","text":["lidocaine hydrochloride"],"offsets":[[218,241]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"19935","type":"Chemical","text":["epinephrine"],"offsets":[[257,268]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"19936","type":"Disease","text":["Muscle degeneration"],"offsets":[[453,472]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"19937","type":"Disease","text":["muscle damage"],"offsets":[[546,559]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"19938","type":"Chemical","text":["mepivacaine"],"offsets":[[639,650]],"normalized":[{"db_name":"MESH","db_id":"D008619"}]},{"id":"19939","type":"Chemical","text":["lidocaine"],"offsets":[[655,664]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"19940","type":"Chemical","text":["epinephrine"],"offsets":[[670,681]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"19941","type":"Disease","text":["diplopia"],"offsets":[[750,758]],"normalized":[{"db_name":"MESH","db_id":"D004172"}]}],"events":[],"coreferences":[],"relations":[{"id":"19942","type":"CID","arg1_id":"19934","arg2_id":"19936","normalized":[]},{"id":"19943","type":"CID","arg1_id":"19934","arg2_id":"19937","normalized":[]},{"id":"19944","type":"CID","arg1_id":"19939","arg2_id":"19936","normalized":[]},{"id":"19945","type":"CID","arg1_id":"19939","arg2_id":"19937","normalized":[]},{"id":"19946","type":"CID","arg1_id":"19933","arg2_id":"19936","normalized":[]},{"id":"19947","type":"CID","arg1_id":"19933","arg2_id":"19937","normalized":[]},{"id":"19948","type":"CID","arg1_id":"19938","arg2_id":"19936","normalized":[]},{"id":"19949","type":"CID","arg1_id":"19938","arg2_id":"19937","normalized":[]},{"id":"19950","type":"CID","arg1_id":"19932","arg2_id":"19936","normalized":[]},{"id":"19951","type":"CID","arg1_id":"19932","arg2_id":"19937","normalized":[]}]}
{"id":"19952","document_id":"2907585","passages":[{"id":"19953","type":"title","text":["Reversal of neuroleptic-induced catalepsy by novel aryl-piperazine anxiolytic drugs."],"offsets":[[0,84]]},{"id":"19954","type":"abstract","text":["The novel anxiolytic drug, buspirone, reverses catalepsy induced by haloperidol. A series of aryl-piperazine analogues of buspirone and other 5-hydroxytryptaminergic agonists were tested for their ability to reverse haloperidol induced catalepsy. Those drugs with strong affinity for 5-hydroxytryptamine1a receptors were able to reverse catalepsy. Drugs with affinity for other 5-HT receptors or weak affinity were ineffective. However, inhibition of postsynaptic 5-HT receptors neither inhibited nor potentiated reversal of catalepsy and leaves open the question as to the site or mechanism for this effect."],"offsets":[[85,693]]}],"entities":[{"id":"19955","type":"Disease","text":["catalepsy"],"offsets":[[32,41]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"19956","type":"Chemical","text":["aryl-piperazine"],"offsets":[[51,66]],"normalized":[]},{"id":"19957","type":"Chemical","text":["buspirone"],"offsets":[[112,121]],"normalized":[{"db_name":"MESH","db_id":"D002065"}]},{"id":"19958","type":"Disease","text":["catalepsy"],"offsets":[[132,141]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"19959","type":"Chemical","text":["haloperidol"],"offsets":[[153,164]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"19960","type":"Chemical","text":["aryl-piperazine"],"offsets":[[178,193]],"normalized":[]},{"id":"19961","type":"Chemical","text":["buspirone"],"offsets":[[207,216]],"normalized":[{"db_name":"MESH","db_id":"D002065"}]},{"id":"19962","type":"Chemical","text":["5-hydroxytryptaminergic agonists"],"offsets":[[227,259]],"normalized":[{"db_name":"MESH","db_id":"D058825"}]},{"id":"19963","type":"Chemical","text":["haloperidol"],"offsets":[[301,312]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"19964","type":"Disease","text":["catalepsy"],"offsets":[[321,330]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"19965","type":"Chemical","text":["5-hydroxytryptamine"],"offsets":[[369,388]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"19966","type":"Disease","text":["catalepsy"],"offsets":[[422,431]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"19967","type":"Chemical","text":["5-HT"],"offsets":[[463,467]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"19968","type":"Chemical","text":["5-HT"],"offsets":[[549,553]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"19969","type":"Disease","text":["catalepsy"],"offsets":[[610,619]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]}],"events":[],"coreferences":[],"relations":[{"id":"19970","type":"CID","arg1_id":"19959","arg2_id":"19955","normalized":[]},{"id":"19971","type":"CID","arg1_id":"19959","arg2_id":"19958","normalized":[]},{"id":"19972","type":"CID","arg1_id":"19959","arg2_id":"19964","normalized":[]},{"id":"19973","type":"CID","arg1_id":"19959","arg2_id":"19966","normalized":[]},{"id":"19974","type":"CID","arg1_id":"19959","arg2_id":"19969","normalized":[]},{"id":"19975","type":"CID","arg1_id":"19963","arg2_id":"19955","normalized":[]},{"id":"19976","type":"CID","arg1_id":"19963","arg2_id":"19958","normalized":[]},{"id":"19977","type":"CID","arg1_id":"19963","arg2_id":"19964","normalized":[]},{"id":"19978","type":"CID","arg1_id":"19963","arg2_id":"19966","normalized":[]},{"id":"19979","type":"CID","arg1_id":"19963","arg2_id":"19969","normalized":[]}]}
{"id":"19980","document_id":"2894433","passages":[{"id":"19981","type":"title","text":["Diazepam facilitates reflex bradycardia in conscious rats."],"offsets":[[0,58]]},{"id":"19982","type":"abstract","text":["The effects of diazepam on cardiovascular function were assessed in conscious rats. Intravenous administration of diazepam (1-30 mg kg-1) produced a dose-dependent decrease in both the mean arterial pressure and the heart rate. Also, reflex bradycardia was produced in rats by intravenous infusion of adrenaline (1.25-2.5 micrograms kg-1). Intravenous pretreatment of the rats with diazepam, although causing no change in the adrenaline-induced pressor effect, did enhance the adrenaline-induced reflex bradycardia. However, the diazepam enhancement of adrenaline-induced reflex bradycardia was antagonized by pretreatment of rats with an intravenous dose of picrotoxin (an agent blocks chloride channels by binding to sites associated with the benzodiazepine-GABA-chloride channel macromolecular complex). The data indicate that diazepam acts through the benzodiazepine-GABA-chloride channel macromolecular complex within the central nervous system to facilitate reflex bradycardia mediated through baroreceptor reflexes in response to an acute increase in arterial pressure."],"offsets":[[59,1135]]}],"entities":[{"id":"19983","type":"Chemical","text":["Diazepam"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"19984","type":"Disease","text":["bradycardia"],"offsets":[[28,39]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"19985","type":"Chemical","text":["diazepam"],"offsets":[[74,82]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"19986","type":"Chemical","text":["diazepam"],"offsets":[[173,181]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"19987","type":"Disease","text":["bradycardia"],"offsets":[[300,311]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"19988","type":"Chemical","text":["adrenaline"],"offsets":[[360,370]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"19989","type":"Chemical","text":["diazepam"],"offsets":[[441,449]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"19990","type":"Chemical","text":["adrenaline"],"offsets":[[485,495]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"19991","type":"Chemical","text":["adrenaline"],"offsets":[[536,546]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"19992","type":"Disease","text":["bradycardia"],"offsets":[[562,573]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"19993","type":"Chemical","text":["diazepam"],"offsets":[[588,596]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"19994","type":"Chemical","text":["adrenaline"],"offsets":[[612,622]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"19995","type":"Disease","text":["bradycardia"],"offsets":[[638,649]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"19996","type":"Chemical","text":["picrotoxin"],"offsets":[[718,728]],"normalized":[{"db_name":"MESH","db_id":"D010852"}]},{"id":"19997","type":"Chemical","text":["chloride"],"offsets":[[746,754]],"normalized":[{"db_name":"MESH","db_id":"D002712"}]},{"id":"19998","type":"Chemical","text":["benzodiazepine"],"offsets":[[804,818]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]},{"id":"19999","type":"Chemical","text":["GABA"],"offsets":[[819,823]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"20000","type":"Chemical","text":["chloride"],"offsets":[[824,832]],"normalized":[{"db_name":"MESH","db_id":"D002712"}]},{"id":"20001","type":"Chemical","text":["diazepam"],"offsets":[[889,897]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"20002","type":"Chemical","text":["benzodiazepine"],"offsets":[[915,929]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]},{"id":"20003","type":"Chemical","text":["GABA"],"offsets":[[930,934]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"20004","type":"Chemical","text":["chloride"],"offsets":[[935,943]],"normalized":[{"db_name":"MESH","db_id":"D002712"}]},{"id":"20005","type":"Disease","text":["bradycardia"],"offsets":[[1030,1041]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]}],"events":[],"coreferences":[],"relations":[{"id":"20006","type":"CID","arg1_id":"19988","arg2_id":"19984","normalized":[]},{"id":"20007","type":"CID","arg1_id":"19988","arg2_id":"19987","normalized":[]},{"id":"20008","type":"CID","arg1_id":"19988","arg2_id":"19992","normalized":[]},{"id":"20009","type":"CID","arg1_id":"19988","arg2_id":"19995","normalized":[]},{"id":"20010","type":"CID","arg1_id":"19988","arg2_id":"20005","normalized":[]},{"id":"20011","type":"CID","arg1_id":"19990","arg2_id":"19984","normalized":[]},{"id":"20012","type":"CID","arg1_id":"19990","arg2_id":"19987","normalized":[]},{"id":"20013","type":"CID","arg1_id":"19990","arg2_id":"19992","normalized":[]},{"id":"20014","type":"CID","arg1_id":"19990","arg2_id":"19995","normalized":[]},{"id":"20015","type":"CID","arg1_id":"19990","arg2_id":"20005","normalized":[]},{"id":"20016","type":"CID","arg1_id":"19991","arg2_id":"19984","normalized":[]},{"id":"20017","type":"CID","arg1_id":"19991","arg2_id":"19987","normalized":[]},{"id":"20018","type":"CID","arg1_id":"19991","arg2_id":"19992","normalized":[]},{"id":"20019","type":"CID","arg1_id":"19991","arg2_id":"19995","normalized":[]},{"id":"20020","type":"CID","arg1_id":"19991","arg2_id":"20005","normalized":[]},{"id":"20021","type":"CID","arg1_id":"19994","arg2_id":"19984","normalized":[]},{"id":"20022","type":"CID","arg1_id":"19994","arg2_id":"19987","normalized":[]},{"id":"20023","type":"CID","arg1_id":"19994","arg2_id":"19992","normalized":[]},{"id":"20024","type":"CID","arg1_id":"19994","arg2_id":"19995","normalized":[]},{"id":"20025","type":"CID","arg1_id":"19994","arg2_id":"20005","normalized":[]},{"id":"20026","type":"CID","arg1_id":"19983","arg2_id":"19984","normalized":[]},{"id":"20027","type":"CID","arg1_id":"19983","arg2_id":"19987","normalized":[]},{"id":"20028","type":"CID","arg1_id":"19983","arg2_id":"19992","normalized":[]},{"id":"20029","type":"CID","arg1_id":"19983","arg2_id":"19995","normalized":[]},{"id":"20030","type":"CID","arg1_id":"19983","arg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{"id":"20056","document_id":"2790457","passages":[{"id":"20057","type":"title","text":["Chronic carbamazepine inhibits the development of local anesthetic seizures kindled by cocaine and lidocaine."],"offsets":[[0,109]]},{"id":"20058","type":"abstract","text":["The effects of carbamazepine (CBZ) treatment on local anesthetic-kindled seizures and lethality were evaluated in different stages of the kindling process and under different methods of CBZ administration. Chronic oral CBZ inhibited the development of both lidocaine- and cocaine-induced seizures, but had little effect on the fully developed local anesthetic seizures. Chronic CBZ also decreased the incidence of seizure-related mortality in the cocaine-injected rats. Acute CBZ over a range of doses (15-50 mg\/kg) had no effect on completed lidocaine-kindled or acute cocaine-induced seizures. Repeated i.p. injection of CBZ (15 mg\/kg) also was without effect on the development of lidocaine- or cocaine-kindled seizures. The differential effects of CBZ depending upon stage of seizure development suggest that distinct mechanisms underlie the development versus maintenance of local anesthetic-kindled seizures. The effectiveness of chronic but not repeated, intermittent injections of CBZ suggests that different biochemical consequences result from the different treatment regimens. The possible utility of chronic CBZ in preventing the development of toxic side effects in human cocaine users is suggested by these data, but remains to be directly evaluated."],"offsets":[[110,1374]]}],"entities":[{"id":"20059","type":"Chemical","text":["carbamazepine"],"offsets":[[8,21]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"20060","type":"Disease","text":["seizures"],"offsets":[[67,75]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"20061","type":"Chemical","text":["cocaine"],"offsets":[[87,94]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"20062","type":"Chemical","text":["lidocaine"],"offsets":[[99,108]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"20063","type":"Chemical","text":["carbamazepine"],"offsets":[[125,138]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"20064","type":"Chemical","text":["CBZ"],"offsets":[[140,143]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"20065","type":"Disease","text":["seizures"],"offsets":[[183,191]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"20066","type":"Chemical","text":["CBZ"],"offsets":[[296,299]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"20067","type":"Chemical","text":["CBZ"],"offsets":[[329,332]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"20068","type":"Chemical","text":["lidocaine"],"offsets":[[367,376]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"20069","type":"Chemical","text":["cocaine"],"offsets":[[382,389]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"20070","type":"Disease","text":["seizures"],"offsets":[[398,406]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"20071","type":"Disease","text":["seizures"],"offsets":[[470,478]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"20072","type":"Chemical","text":["CBZ"],"offsets":[[488,491]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"20073","type":"Disease","text":["seizure"],"offsets":[[524,531]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"20074","type":"Chemical","text":["cocaine"],"offsets":[[557,564]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"20075","type":"Chemical","text":["CBZ"],"offsets":[[586,589]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"20076","type":"Chemical","text":["lidocaine"],"offsets":[[653,662]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"20077","type":"Chemical","text":["cocaine"],"offsets":[[680,687]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"20078","type":"Disease","text":["seizures"],"offsets":[[696,704]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"20079","type":"Chemical","text":["CBZ"],"offsets":[[733,736]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"20080","type":"Chemical","text":["lidocaine"],"offsets":[[794,803]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"20081","type":"Chemical","text":["cocaine"],"offsets":[[808,815]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"20082","type":"Disease","text":["seizures"],"offsets":[[824,832]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"20083","type":"Chemical","text":["CBZ"],"offsets":[[862,865]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"20084","type":"Disease","text":["seizure"],"offsets":[[890,897]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"20085","type":"Disease","text":["seizures"],"offsets":[[1015,1023]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"20086","type":"Chemical","text":["CBZ"],"offsets":[[1099,1102]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"20087","type":"Chemical","text":["CBZ"],"offsets":[[1230,1233]],"normalized":[{"db_name":"MESH","db_id":"D002220"}]},{"id":"20088","type":"Chemical","text":["cocaine"],"offsets":[[1295,1302]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]}],"events":[],"coreferences":[],"relations":[{"id":"20089","type":"CID","arg1_id":"20062","arg2_id":"20060","normalized":[]},{"id":"20090","type":"CID","arg1_id":"20062","arg2_id":"20065","normalized":[]},{"id":"20091","type":"CID","arg1_id":"20062","arg2_id":"20070","normalized":[]},{"id":"20092","type":"CID","arg1_id":"20062","arg2_id":"20071","normalized":[]},{"id":"20093","type":"CID","arg1_id":"20062","arg2_id":"20073","normalized":[]},{"id":"20094","type":"CID","arg1_id":"20062","arg2_id":"20078","normalized":[]},{"id":"20095","type":"CID","arg1_id":"20062","arg2_id":"20082","normalized":[]},{"id":"20096","type":"CID","arg1_id":"20062","arg2_id":"20084","normalized":[]},{"id":"20097","type":"CID","arg1_id":"20062","arg2_id":"20085","normalized":[]},{"id":"20098","type":"CID","arg1_id":"20068","arg2_id":"20060","normalized":[]},{"id":"20099","type":"CID","arg1_id":"20068","arg2_id":"20065","normalized":[]},{"id":"20100","type":"CID","arg1_id":"20068","arg2_id":"20070","normalized":[]},{"id":"20101","type":"CID","arg1_id":"20068","arg2_id":"20071","normalized":[]},{"id":"20102","type":"CID","arg1_id":"20068","arg2_id":"20073","normalized":[]},{"id":"20103","type":"CI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{"id":"20179","document_id":"2334179","passages":[{"id":"20180","type":"title","text":["D-penicillamine in the treatment of localized scleroderma."],"offsets":[[0,58]]},{"id":"20181","type":"abstract","text":["Localized scleroderma has no recognized internal organ involvement but may be disfiguring and disabling when the cutaneous lesions are extensive or affect children. There is no accepted or proven treatment for localized scleroderma. Case reports of 11 patients with severe, extensive localized scleroderma who were treated with D-penicillamine are summarized in this article. This drug was judged to have a favorable effect on the disease course in 7 (64%) of 11 patients. Improvement began within 3 to 6 months and consisted of cessation of active cutaneous lesions in all 7 patients, skin softening in 5, and more normal growth of the affected limb in 2 of 3 children. Joint stiffness and contractures also improved. The dose of D-penicillamine associated with a favorable response was as low as 2 to 5 mg\/kg per day given over a period ranging from 15 to 53 months. D-Penicillamine caused nephrotic syndrome in 1 patient and milder reversible proteinuria in 3 other patients; none developed renal insufficiency. These data suggest that D-penicillamine may be effective in severe cases of localized scleroderma."],"offsets":[[59,1172]]}],"entities":[{"id":"20182","type":"Chemical","text":["D-penicillamine"],"offsets":[[0,15]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"20183","type":"Disease","text":["localized scleroderma"],"offsets":[[36,57]],"normalized":[{"db_name":"MESH","db_id":"D012594"}]},{"id":"20184","type":"Disease","text":["Localized scleroderma"],"offsets":[[59,80]],"normalized":[{"db_name":"MESH","db_id":"D012594"}]},{"id":"20185","type":"Disease","text":["localized scleroderma"],"offsets":[[269,290]],"normalized":[{"db_name":"MESH","db_id":"D012594"}]},{"id":"20186","type":"Disease","text":["localized scleroderma"],"offsets":[[343,364]],"normalized":[{"db_name":"MESH","db_id":"D012594"}]},{"id":"20187","type":"Chemical","text":["D-penicillamine"],"offsets":[[387,402]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"20188","type":"Disease","text":["contractures"],"offsets":[[750,762]],"normalized":[{"db_name":"MESH","db_id":"D003286"}]},{"id":"20189","type":"Chemical","text":["D-penicillamine"],"offsets":[[790,805]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"20190","type":"Chemical","text":["D-Penicillamine"],"offsets":[[928,943]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"20191","type":"Disease","text":["nephrotic syndrome"],"offsets":[[951,969]],"normalized":[{"db_name":"MESH","db_id":"D009404"}]},{"id":"20192","type":"Disease","text":["proteinuria"],"offsets":[[1005,1016]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"20193","type":"Disease","text":["renal insufficiency"],"offsets":[[1053,1072]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"20194","type":"Chemical","text":["D-penicillamine"],"offsets":[[1098,1113]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"20195","type":"Disease","text":["localized scleroderma"],"offsets":[[1150,1171]],"normalized":[{"db_name":"MESH","db_id":"D012594"}]}],"events":[],"coreferences":[],"relations":[{"id":"20196","type":"CID","arg1_id":"20182","arg2_id":"20191","normalized":[]},{"id":"20197","type":"CID","arg1_id":"20187","arg2_id":"20191","normalized":[]},{"id":"20198","type":"CID","arg1_id":"20189","arg2_id":"20191","normalized":[]},{"id":"20199","type":"CID","arg1_id":"20190","arg2_id":"20191","normalized":[]},{"id":"20200","type":"CID","arg1_id":"20194","arg2_id":"20191","normalized":[]},{"id":"20201","type":"CID","arg1_id":"20182","arg2_id":"20192","normalized":[]},{"id":"20202","type":"CID","arg1_id":"20187","arg2_id":"20192","normalized":[]},{"id":"20203","type":"CID","arg1_id":"20189","arg2_id":"20192","normalized":[]},{"id":"20204","type":"CID","arg1_id":"20190","arg2_id":"20192","normalized":[]},{"id":"20205","type":"CID","arg1_id":"20194","arg2_id":"20192","normalized":[]}]}
{"id":"20206","document_id":"1969772","passages":[{"id":"20207","type":"title","text":["Preservation of renal blood flow during hypotension induced with fenoldopam in dogs."],"offsets":[[0,84]]},{"id":"20208","type":"abstract","text":["The introduction of drugs that could induce hypotension with different pharmacological actions would be advantageous because side effects unique to a specific drug could be minimized by selecting appropriate therapy. Specific dopamine-1, (DA1) and dopamine-2 (DA2) receptor agonists are now under clinical investigation. Fenoldopam mesylate is a specific DA1 receptor agonist that lowers blood pressure by vasodilatation. The hypothesis that fenoldopam could be used to induce hypotension and preserve blood flow to the kidney was tested. Systemic aortic blood pressure and renal blood flow were measured continuously with a carotid arterial catheter and an electromagnetic flow probe respectively, in order to compare the cardiovascular and renal vascular effects of fenoldopam and sodium nitroprusside in ten dogs under halothane general anaesthesia. Mean arterial pressure was decreased 30 +\/- 8 per cent from control with infusion of fenoldopam (3.4 +\/- 2.0 micrograms.kg-1.min-1) and 34 +\/- 4 per cent with infusion of sodium nitroprusside (5.9 micrograms.kg-1.min-1) (NS). Renal blood flow (RBF) increased during fenoldopam-induced hypotension 11 +\/- 7 per cent and decreased 21 +\/- 8 per cent during sodium nitroprusside-induced hypotension (P less than 0.01). Sodium nitroprusside is a non-selective arteriolar and venous vasodilator that can produce redistribution of blood flow away from the kidney during induced hypotension. Fenoldopam is a selective dopamine-1 (DA1) receptor agonist that causes vasodilatation to the kidney and other organs with DA1 receptors and preserves blood flow to the kidney during induced hypotension."],"offsets":[[85,1725]]}],"entities":[{"id":"20209","type":"Disease","text":["hypotension"],"offsets":[[40,51]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"20210","type":"Chemical","text":["fenoldopam"],"offsets":[[65,75]],"normalized":[{"db_name":"MESH","db_id":"D018818"}]},{"id":"20211","type":"Disease","text":["hypotension"],"offsets":[[129,140]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"20212","type":"Chemical","text":["dopamine"],"offsets":[[311,319]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"20213","type":"Chemical","text":["DA"],"offsets":[[324,326]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"20214","type":"Chemical","text":["dopamine"],"offsets":[[333,341]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"20215","type":"Chemical","text":["DA"],"offsets":[[345,347]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"20216","type":"Chemical","text":["Fenoldopam 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{"id":"20312","document_id":"1700207","passages":[{"id":"20313","type":"title","text":["Antiarrhythmic effects of optical isomers of cibenzoline on canine ventricular arrhythmias."],"offsets":[[0,91]]},{"id":"20314","type":"abstract","text":["Antiarrhythmic effects of (+)-cibenzoline and (-)-cibenzoline were examined using two canine ventricular arrhythmia models. Digitalis arrhythmia, which is suppressed by Na channel blockers, was induced by intermittent intravenous (i.v.) injection of ouabain in pentobarbital-anesthetized dogs. Adrenaline arrhythmia, which is suppressed by Ca channel blockers, was induced by adrenaline infusion in halothane-anesthetized dogs. Ten and 5 mg\/kg i.v. (+)-cibenzoline suppressed digitalis- and adrenaline-induced arrhythmias, respectively. The minimum effective plasma concentrations of (+)-cibenzoline for digitalis- and adrenaline-induced arrhythmias were 1.4 +\/- 0.4 and 2.0 +\/- 0.6 micrograms\/ml, respectively (mean +\/- SD, n = 6). A lower dose of 1 mg\/kg i.v. of (-)-cibenzoline suppressed the digitalis-induced arrhythmia, whereas 5 mg\/kg i.v. was needed to suppress adrenaline-induced arrhythmias. The minimum effective plasma concentrations of (-)-cibenzoline for digitalis- and adrenaline-induced arrhythmia were 0.06 +\/- 0.04 and 0.7 +\/- 0.1 micrograms\/ml, respectively (mean +\/- SD, n = 6). The stronger antiarrhythmic effect of (-)-cibenzoline indicates that (-)-isomer may have an effect nearly 5-20 times stronger in suppressing Na channels, but effects of both drugs on Ca channels may be almost equipotent."],"offsets":[[92,1411]]}],"entities":[{"id":"20315","type":"Chemical","text":["cibenzoline"],"offsets":[[45,56]],"normalized":[{"db_name":"MESH","db_id":"C032151"}]},{"id":"20316","type":"Disease","text":["ventricular arrhythmias"],"offsets":[[67,90]],"normalized":[{"db_name":"MESH","db_id":"D001145"}]},{"id":"20317","type":"Chemical","text":["cibenzoline"],"offsets":[[122,133]],"normalized":[{"db_name":"MESH","db_id":"C032151"}]},{"id":"20318","type":"Chemical","text":["cibenzoline"],"offsets":[[142,153]],"normalized":[{"db_name":"MESH","db_id":"C032151"}]},{"id":"20319","type":"Disease","text":["ventricular 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{"id":"20403","document_id":"19761039","passages":[{"id":"20404","type":"title","text":["Effect of Hibiscus rosa sinensis on reserpine-induced neurobehavioral and biochemical alterations in rats."],"offsets":[[0,106]]},{"id":"20405","type":"abstract","text":["Effect of methanolic extract of Hibiscus rosa sinensis (100-300 mg\/kg) was studied on reserpine-induced orofacial dyskinesia and neurochemical alterations. The rats were treated with intraperitoneal reserpine (1 mg\/kg, ip) for 3 days every other day. On day 5, vacuous chewing movements and tongue protrusions were counted for 5 min. Reserpine treated rats significantly developed vacuous chewing movements and tongue protrusions however, coadministration of Hibiscus rosa sinensis roots extract (100, 200 and 300 mg\/kg, per orally) attenuated the effects. Biochemical analysis of brain revealed that the reserpine treatment significantly increased lipid peroxidation and decreased levels of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GSH), an index of oxidative stress process. Coadministration of extract significantly reduced the lipid peroxidation and reversed the decrease in brain SOD, CAT and GSH levels. The results of the present study suggested that Hibiscus rosa sinensis had a protective role against reserpine-induced orofacial dyskinesia and oxidative stress."],"offsets":[[107,1207]]}],"entities":[{"id":"20406","type":"Chemical","text":["Hibiscus rosa sinensis"],"offsets":[[10,32]],"normalized":[{"db_name":"MESH","db_id":"D010936"}]},{"id":"20407","type":"Chemical","text":["reserpine"],"offsets":[[36,45]],"normalized":[{"db_name":"MESH","db_id":"D012110"}]},{"id":"20408","type":"Chemical","text":["Hibiscus rosa sinensis"],"offsets":[[139,161]],"normalized":[{"db_name":"MESH","db_id":"D010936"}]},{"id":"20409","type":"Chemical","text":["reserpine"],"offsets":[[193,202]],"normalized":[{"db_name":"MESH","db_id":"D012110"}]},{"id":"20410","type":"Disease","text":["dyskinesia"],"offsets":[[221,231]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"20411","type":"Chemical","text":["reserpine"],"offsets":[[306,315]],"normalized":[{"db_name":"MESH","db_id":"D012110"}]},{"id":"20412","type":"Chemical","text":["Reserpine"],"offsets":[[441,450]],"normalized":[{"db_name":"MESH","db_id":"D012110"}]},{"id":"20413","type":"Chemical","text":["Hibiscus rosa sinensis"],"offsets":[[566,588]],"normalized":[{"db_name":"MESH","db_id":"D010936"}]},{"id":"20414","type":"Chemical","text":["reserpine"],"offsets":[[712,721]],"normalized":[{"db_name":"MESH","db_id":"D012110"}]},{"id":"20415","type":"Chemical","text":["superoxide"],"offsets":[[799,809]],"normalized":[{"db_name":"MESH","db_id":"D013481"}]},{"id":"20416","type":"Chemical","text":["glutathione"],"offsets":[[846,857]],"normalized":[{"db_name":"MESH","db_id":"D005978"}]},{"id":"20417","type":"Chemical","text":["Hibiscus rosa sinensis"],"offsets":[[1094,1116]],"normalized":[{"db_name":"MESH","db_id":"D010936"}]},{"id":"20418","type":"Chemical","text":["reserpine"],"offsets":[[1147,1156]],"normalized":[{"db_name":"MESH","db_id":"D012110"}]},{"id":"20419","type":"Disease","text":["dyskinesia"],"offsets":[[1175,1185]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]}],"events":[],"coreferences":[],"relations":[{"id":"20420","type":"CID","arg1_id":"20407","arg2_id":"20410","normalized":[]},{"id":"20421","type":"CID","arg1_id":"20407","arg2_id":"20419","normalized":[]},{"id":"20422","type":"CID","arg1_id":"20409","arg2_id":"20410","normalized":[]},{"id":"20423","type":"CID","arg1_id":"20409","arg2_id":"20419","normalized":[]},{"id":"20424","type":"CID","arg1_id":"20411","arg2_id":"20410","normalized":[]},{"id":"20425","type":"CID","arg1_id":"20411","arg2_id":"20419","normalized":[]},{"id":"20426","type":"CID","arg1_id":"20412","arg2_id":"20410","normalized":[]},{"id":"20427","type":"CID","arg1_id":"20412","arg2_id":"20419","normalized":[]},{"id":"20428","type":"CID","arg1_id":"20414","arg2_id":"20410","normalized":[]},{"id":"20429","type":"CID","arg1_id":"20414","arg2_id":"20419","normalized":[]},{"id":"20430","type":"CID","arg1_id":"20418","arg2_id":"20410","normalized":[]},{"id":"20431","type":"CID","arg1_id":"20418","arg2_id":"20419","normalized":[]}]}
{"id":"20432","document_id":"11704023","passages":[{"id":"20433","type":"title","text":["Comparison of aqueous and gellan ophthalmic timolol with placebo on the 24-hour heart rate response in patients on treatment for glaucoma."],"offsets":[[0,138]]},{"id":"20434","type":"abstract","text":["PURPOSE: Topical beta-blocker treatment is routine therapy in the management of patients with glaucoma. Therapy results in systemic absorption, however, the degree of reduction of resting and peak heart rate has not been quantified. DESIGN: This trial evaluated the effect of placebo, 0.5% aqueous timolol (timolol solution) and a 0.5% timolol suspension that forms a gel on application to the conjunctiva (timolol gellan) on the 24-hour heart rate in patients currently being treated for glaucoma to quantify the reduction in mean heart rate. METHODS: Forty-three Caucasian patients with primary open-angle glaucoma or ocular hypertension with a mean (+\/-SD) age of 63 (+\/-8) years were randomized and crossed over in a double-masked manner to 14 days of treatment with placebo (morning and evening in both eyes), timolol solution (morning and evening in both eyes), or timolol gellan (morning in both eyes with placebo in the evening). On the 13th day of each period, heart rate was recorded continuously during a typical, ambulant 24-hour period. RESULTS: Both timolol solution and timolol gellan reduced the mean 24-hour heart rate compared with placebo (P < or = .001), and this reduction was most pronounced during the daytime (-7.5% change in mean heart rate, -5.7 beats\/min). Timolol gellan showed a numerically but not significantly smaller reduction in 24-hour heart rate, compared with timolol solution. During the night, the mean 12-hour heart rate on placebo and timolol gellan were both significantly less than on timolol solution; the difference between solution and gellan treatments was statistically significant (P = .01). CONCLUSIONS: Both timolol solution and timolol gellan decrease the mean 24-hour heart rate compared with placebo. This response was most pronounced during the active daytime period. These data quantify the modest bradycardia associated with ophthalmic beta-blocker therapy in a typical patient population on therapy for glaucoma. Although exercise performance was not assessed in this trial, reductions of this magnitude should not have substantial clinical consequences."],"offsets":[[139,2251]]}],"entities":[{"id":"20435","type":"Chemical","text":["timolol"],"offsets":[[44,51]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"20436","type":"Disease","text":["glaucoma"],"offsets":[[129,137]],"normalized":[{"db_name":"MESH","db_id":"D005901"}]},{"id":"20437","type":"Disease","text":["glaucoma"],"offsets":[[233,241]],"normalized":[{"db_name":"MESH","db_id":"D005901"}]},{"id":"20438","type":"Chemical","text":["timolol"],"offsets":[[437,444]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"20439","type":"Chemical","text":["timolol"],"offsets":[[446,453]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"20440","type":"Chemical","text":["timolol"],"offsets":[[475,482]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"20441","type":"Chemical","text":["timolol"],"offsets":[[546,553]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"20442","type":"Disease","text":["glaucoma"],"offsets":[[628,636]],"normalized":[{"db_name":"MESH","db_id":"D005901"}]},{"id":"20443","type":"Disease","text":["open-angle glaucoma"],"offsets":[[736,755]],"normalized":[{"db_name":"MESH","db_id":"D005902"}]},{"id":"20444","type":"Disease","text":["ocular hypertension"],"offsets":[[759,778]],"normalized":[{"db_name":"MESH","db_id":"D009798"}]},{"id":"20445","type":"Chemical","text":["timolol"],"offsets":[[954,961]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"20446","type":"Chemical","text":["timolol"],"offsets":[[1010,1017]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"20447","type":"Chemical","text":["timolol"],"offsets":[[1203,1210]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"20448","type":"Chemical","text":["timolol"],"offsets":[[1224,1231]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"20449","type":"Chemical","text":["Timolol"],"offsets":[[1423,1430]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"20450","type":"Chemical","text":["timolol"],"offsets":[[1536,1543]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"20451","type":"Chemical","text":["timolol"],"offsets":[[1615,1622]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"20452","type":"Chemical","text":["timolol"],"offsets":[[1667,1674]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"20453","type":"Chemical","text":["timolol"],"offsets":[[1798,1805]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"20454","type":"Chemical","text":["timolol"],"offsets":[[1819,1826]],"normalized":[{"db_name":"MESH","db_id":"D013999"}]},{"id":"20455","type":"Disease","text":["bradycardia"],"offsets":[[1993,2004]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"20456","type":"Disease","text":["glaucoma"],"offsets":[[2100,2108]],"normalized":[{"db_name":"MESH","db_id":"D005901"}]}],"events":[],"coreferences":[],"relations":[{"id":"20457","type":"CID","arg1_id":"20435","arg2_id":"20455","normalized":[]},{"id":"20458","type":"CID","arg1_id":"20438","arg2_id":"20455","normalized":[]},{"id":"20459","type":"CID","arg1_id":"20439","arg2_id":"20455","normalized":[]},{"id":"20460","type":"CID","arg1_id":"20440","arg2_id":"20455","normalized":[]},{"id":"20461","type":"CID","arg1_id":"20441","arg2_id":"20455","normalized":[]},{"id":"20462","type":"CID","arg1_id":"20445","arg2_id":"20455","normalized":[]},{"id":"20463","type":"CID","arg1_id":"20446","arg2_id":"20455","normalized":[]},{"id":"20464","type":"CID","arg1_id":"20447","arg2_id":"20455","normalized":[]},{"id":"20465","type":"CID","arg1_id":"20448","arg2_id":"20455","normalized":[]},{"id":"20466","type":"CID","arg1_id":"20449","arg2_id":"20455","normalized":[]},{"id":"20467","type":"CID","arg1_id":"20450","arg2_id":"20455","normalized":[]},{"id":"20468","type":"CID","arg1_id":"20451","arg2_id":"20455","normalized":[]},{"id":"20469","type":"CID","arg1_id":"20452","arg2_id":"20455","normalized":[]},{"id":"20470","type":"CID","arg1_id":"20453","arg2_id":"20455","normalized":[]},{"id":"20471","type":"CID","arg1_id":"20454","arg2_id":"20455","normalized":[]}]}
{"id":"20472","document_id":"19300240","passages":[{"id":"20473","type":"title","text":["5 flourouracil-induced apical ballooning syndrome: a case report."],"offsets":[[0,65]]},{"id":"20474","type":"abstract","text":["The apical ballooning syndrome (ABS) is a recently described stress-mediated acute cardiac syndrome characterized by transient wall-motion abnormalities involving the apex and midventricle with hyperkinesis of the basal left ventricular (LV) segments without obstructive epicardial coronary disease. Cardiotoxicity is not an uncommon adverse effect of chemotherapeutic agents. However, there are no reports of ABS secondary to chemotherapeutic agents. We describe the case of a woman who developed the syndrome after chemotherapy for metastatic cancer. A 79-year-old woman presented with typical ischemic chest pain, elevated cardiac enzymes with significant ST-segment abnormalities on her electrocardiogram. She underwent recent chemotherapy with fluorouracil for metastatic colorectal cancer. Echocardiography revealed a wall-motion abnormality involving the apical and periapical segments which appeared akinetic. Coronary angiography revealed no obstructive coronary lesions. The patient was stabilized with medical therapy. Four weeks later she remained completely asymptomatic. Echocardiogram revealed a normal ejection fraction and a resolution of the apical akinesis. Pathogenetic mechanisms of cardiac complications in cancer patients undergoing chemotherapy include coronary vasospasm, endothelial damage and consequent thrombus formation. In our patient, both supraphysiologic levels of plasma catecholamines and stress related neuropeptides caused by cancer diagnosis as well as chemotherapy may have contributed the development of ABS."],"offsets":[[66,1615]]}],"entities":[{"id":"20475","type":"Chemical","text":["5 flourouracil"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"20476","type":"Disease","text":["apical ballooning syndrome"],"offsets":[[23,49]],"normalized":[{"db_name":"MESH","db_id":"D054549"}]},{"id":"20477","type":"Disease","text":["apical ballooning syndrome"],"offsets":[[70,96]],"normalized":[{"db_name":"MESH","db_id":"D054549"}]},{"id":"20478","type":"Disease","text":["ABS"],"offsets":[[98,101]],"normalized":[{"db_name":"MESH","db_id":"D054549"}]},{"id":"20479","type":"Disease","text":["acute cardiac syndrome"],"offsets":[[143,165]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"20480","type":"Disease","text":["hyperkinesis"],"offsets":[[260,272]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"20481","type":"Disease","text":["epicardial coronary disease"],"offsets":[[337,364]],"normalized":[{"db_name":"MESH","db_id":"D003327"}]},{"id":"20482","type":"Disease","text":["Cardiotoxicity"],"offsets":[[366,380]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"20483","type":"Disease","text":["ABS"],"offsets":[[476,479]],"normalized":[{"db_name":"MESH","db_id":"D054549"}]},{"id":"20484","type":"Disease","text":["cancer"],"offsets":[[611,617]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"20485","type":"Disease","text":["ischemic"],"offsets":[[662,670]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"20486","type":"Disease","text":["chest pain"],"offsets":[[671,681]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"20487","type":"Chemical","text":["fluorouracil"],"offsets":[[815,827]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"20488","type":"Disease","text":["colorectal cancer"],"offsets":[[843,860]],"normalized":[{"db_name":"MESH","db_id":"D015179"}]},{"id":"20489","type":"Disease","text":["akinetic"],"offsets":[[974,982]],"normalized":[{"db_name":"MESH","db_id":"D018476"}]},{"id":"20490","type":"Disease","text":["akinesis"],"offsets":[[1233,1241]],"normalized":[{"db_name":"MESH","db_id":"D018476"}]},{"id":"20491","type":"Disease","text":["cardiac complications"],"offsets":[[1270,1291]],"normalized":[{"db_name":"MESH","db_id":"D005117"}]},{"id":"20492","type":"Disease","text":["cancer"],"offsets":[[1295,1301]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"20493","type":"Disease","text":["coronary vasospasm"],"offsets":[[1343,1361]],"normalized":[{"db_name":"MESH","db_id":"D003329"}]},{"id":"20494","type":"Disease","text":["thrombus"],"offsets":[[1397,1405]],"normalized":[{"db_name":"MESH","db_id":"D013927"}]},{"id":"20495","type":"Chemical","text":["catecholamines"],"offsets":[[1472,1486]],"normalized":[{"db_name":"MESH","db_id":"D002395"}]},{"id":"20496","type":"Disease","text":["cancer"],"offsets":[[1530,1536]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"20497","type":"Disease","text":["ABS"],"offsets":[[1611,1614]],"normalized":[{"db_name":"MESH","db_id":"D054549"}]}],"events":[],"coreferences":[],"relations":[{"id":"20498","type":"CID","arg1_id":"20475","arg2_id":"20476","normalized":[]},{"id":"20499","type":"CID","arg1_id":"20475","arg2_id":"20477","normalized":[]},{"id":"20500","type":"CID","arg1_id":"20475","arg2_id":"20478","normalized":[]},{"id":"20501","type":"CID","arg1_id":"20475","arg2_id":"20483","normalized":[]},{"id":"20502","type":"CID","arg1_id":"20475","arg2_id":"20497","normalized":[]},{"id":"20503","type":"CID","arg1_id":"20487","arg2_id":"20476","normalized":[]},{"id":"20504","type":"CID","arg1_id":"20487","arg2_id":"20477","normalized":[]},{"id":"20505","type":"CID","arg1_id":"20487","arg2_id":"20478","normalized":[]},{"id":"20506","type":"CID","arg1_id":"20487","arg2_id":"20483","normalized":[]},{"id":"20507","type":"CID","arg1_id":"20487","arg2_id":"20497","normalized":[]},{"id":"20508","type":"CID","arg1_id":"20475","arg2_id":"20486","normalized":[]},{"id":"20509","type":"CID","arg1_id":"20487","arg2_id":"20486","normalized":[]}]}
{"id":"20510","document_id":"18006530","passages":[{"id":"20511","type":"title","text":["Reduction of pain during induction with target-controlled propofol and remifentanil."],"offsets":[[0,84]]},{"id":"20512","type":"abstract","text":["BACKGROUND: Pain on injection of propofol is unpleasant. We hypothesized that propofol infusion pain might be prevented by infusing remifentanil before starting the propofol infusion in a clinical setting where target-controlled infusions (TCI) of both drugs were used. A prospective, randomized, double-blind, placebo-controlled trial was performed to determine the effect-site concentration (Ce) of remifentanil to prevent the pain without producing complications. METHODS: A total of 128 patients undergoing general surgery were randomly allocated to receive normal saline (control) or remifentanil to a target Ce of 2 ng ml(-1) (R2), 4 ng ml(-1) (R4), or 6 ng ml(-1) (R6) administered via TCI. After the target Ce was achieved, the infusion of propofol was started. Remifentanil-related complications were assessed during the remifentanil infusion, and pain caused by propofol was evaluated using a four-point scale during the propofol infusion. RESULTS: The incidence of pain was significantly lower in Groups R4 and R6 than in the control and R2 groups (12\/32 and 6\/31 vs 26\/31 and 25\/32, respectively, P<0.001). Pain was less severe in Groups R4 and R6 than in the control and R2 groups (P<0.001). However, both incidence and severity of pain were not different between Groups R4 and R6. No significant complications were observed during the study. CONCLUSIONS: During induction of anaesthesia with TCI of propofol and remifentanil, a significant reduction in propofol infusion pain was achieved without significant complications by prior administration of remifentanil at a target Ce of 4 ng ml(-1)."],"offsets":[[85,1692]]}],"entities":[{"id":"20513","type":"Disease","text":["pain"],"offsets":[[13,17]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"20514","type":"Chemical","text":["propofol"],"offsets":[[58,66]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"20515","type":"Chemical","text":["remifentanil"],"offsets":[[71,83]],"normalized":[{"db_name":"MESH","db_id":"C071741"}]},{"id":"20516","type":"Disease","text":["Pain"],"offsets":[[97,101]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"20517","type":"Chemical","text":["propofol"],"offsets":[[118,126]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"20518","type":"Chemical","text":["propofol"],"offsets":[[163,171]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"20519","type":"Disease","text":["pain"],"offsets":[[181,185]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"20520","type":"Chemical","text":["remifentanil"],"offsets":[[217,229]],"normalized":[{"db_name":"MESH","db_id":"C071741"}]},{"id":"20521","type":"Chemical","text":["propofol"],"offsets":[[250,258]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"20522","type":"Chemical","text":["remifentanil"],"offsets":[[486,498]],"normalized":[{"db_name":"MESH","db_id":"C071741"}]},{"id":"20523","type":"Disease","text":["pain"],"offsets":[[514,518]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"20524","type":"Chemical","text":["remifentanil"],"offsets":[[674,686]],"normalized":[{"db_name":"MESH","db_id":"C071741"}]},{"id":"20525","type":"Chemical","text":["propofol"],"offsets":[[833,841]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"20526","type":"Chemical","text":["Remifentanil"],"offsets":[[855,867]],"normalized":[{"db_name":"MESH","db_id":"C071741"}]},{"id":"20527","type":"Chemical","text":["remifentanil"],"offsets":[[915,927]],"normalized":[{"db_name":"MESH","db_id":"C071741"}]},{"id":"20528","type":"Disease","text":["pain"],"offsets":[[942,946]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"20529","type":"Chemical","text":["propofol"],"offsets":[[957,965]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"20530","type":"Chemical","text":["propofol"],"offsets":[[1016,1024]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"20531","type":"Disease","text":["pain"],"offsets":[[1061,1065]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"20532","type":"Disease","text":["Pain"],"offsets":[[1204,1208]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"20533","type":"Disease","text":["pain"],"offsets":[[1330,1334]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"20534","type":"Chemical","text":["propofol"],"offsets":[[1498,1506]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"20535","type":"Chemical","text":["remifentanil"],"offsets":[[1511,1523]],"normalized":[{"db_name":"MESH","db_id":"C071741"}]},{"id":"20536","type":"Chemical","text":["propofol"],"offsets":[[1552,1560]],"normalized":[{"db_name":"MESH","db_id":"D015742"}]},{"id":"20537","type":"Disease","text":["pain"],"offsets":[[1570,1574]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"20538","type":"Chemical","text":["remifentanil"],"offsets":[[1649,1661]],"normalized":[{"db_name":"MESH","db_id":"C071741"}]}],"events":[],"coreferences":[],"relations":[{"id":"20539","type":"CID","arg1_id":"20514","arg2_id":"20513","normalized":[]},{"id":"20540","type":"CID","arg1_id":"20514","arg2_id":"20516","normalized":[]},{"id":"20541","type":"CID","arg1_id":"20514","arg2_id":"20519","normalized":[]},{"id":"20542","type":"CID","arg1_id":"20514","arg2_id":"20523","normalized":[]},{"id":"20543","type":"CID","arg1_id":"20514","arg2_id":"20528","normalized":[]},{"id":"20544","type":"CID","arg1_id":"20514","arg2_id":"20531","normalized":[]},{"id":"20545","type":"CID","arg1_id":"20514","arg2_id":"20532","normalized":[]},{"id":"20546","type":"CID","arg1_id":"20514","arg2_id":"20533","normalized":[]},{"id":"20547","type":"CID","arg1_id":"20514","arg2_id":"20537","normalized":[]},{"id":"20548","type":"CID","arg1_id":"20517","arg2_id":"20513","normalized":[]},{"id":"20549","type":"CID","arg1_id":"20517","arg2_id":"20516","normalized":[]},{"id":"20550","type":"CID","arg1_id":"20517","arg2_id":"20519","normalized":[]},{"id":"20551","type":"CID","arg1_id":"20517","arg2_id":"20523","normalized":[]},{"id":"20552","type":"CID","arg1_id":"20517","arg2_id":"20528","normalized":[]},{"id":"20553","type":"CID","arg1_id":"20517","arg2_id":"20531","normalized":[]},{"id":"20554","type":"CID","arg1_id":"20517","arg2_id":"20532","normalized":[]},{"id":"20555","type":"CID","arg1_id":"20517","arg2_id":"20533","normalized":[]},{"id":"20556","type":"CID","arg1_id":"20517","arg2_id":"20537","normalized":[]},{"id":"20557","type":"CID","arg1_id":"20518","arg2_id":"20513","normalized":[]},{"id":"20558","type":"CID","arg1_id":"20518","arg2_id":"20516","normalized":[]},{"id":"205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{"id":"20620","document_id":"17702969","passages":[{"id":"20621","type":"title","text":["Prenatal exposure to fluoxetine induces fetal pulmonary hypertension in the rat."],"offsets":[[0,80]]},{"id":"20622","type":"abstract","text":["RATIONALE: Fluoxetine is a selective serotonin reuptake inhibitor antidepressant widely used by pregnant women. Epidemiological data suggest that fluoxetine exposure prenatally increases the prevalence of persistent pulmonary hypertension syndrome of the newborn. The mechanism responsible for this effect is unclear and paradoxical, considering the current evidence of a pulmonary hypertension protective fluoxetine effect in adult rodents. OBJECTIVES: To evaluate the fluoxetine effect on fetal rat pulmonary vascular smooth muscle mechanical properties and cell proliferation rate. METHODS: Pregnant rats were treated with fluoxetine (10 mg\/kg) from Day 11 through Day 21 of gestation. MEASUREMENTS AND MAIN RESULTS: Fetuses were delivered by cesarean section. As compared with controls, fluoxetine exposure resulted in fetal pulmonary hypertension as evidenced by an increase in the weight ratio of the right ventricle to the left ventricle plus septum (P = 0.02) and by an increase in pulmonary arterial medial thickness (P < 0.01). Postnatal mortality was increased among experimental animals, and arterial oxygen saturation was 96 +\/- 1% in 1-day-old control animals and significantly lower (P < 0.01) in fluoxetine-exposed pups (79 +\/- 2%). In vitro, fluoxetine induced pulmonary arterial muscle contraction in fetal, but not adult, animals (P < 0.01) and reduced serotonin-induced contraction at both ages (P < 0.01). After in utero exposure to a low fluoxetine concentration the pulmonary arterial smooth muscle cell proliferation rate was significantly increased in fetal, but not adult, cells (P < 0.01). CONCLUSIONS: In contrast to the adult, fluoxetine exposure in utero induces pulmonary hypertension in the fetal rat as a result of a developmentally regulated increase in pulmonary vascular smooth muscle proliferation."],"offsets":[[81,1916]]}],"entities":[{"id":"20623","type":"Chemical","text":["fluoxetine"],"offsets":[[21,31]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"20624","type":"Disease","text":["fetal pulmonary hypertension"],"offsets":[[40,68]],"normalized":[{"db_name":"MESH","db_id":"D005315"},{"db_name":"MESH","db_id":"D006976"}]},{"id":"20625","type":"Disease","text":["fetal pulmonary hypertension"],"offsets":[[40,68]],"normalized":[{"db_name":"MESH","db_id":"D005315"}]},{"id":"20626","type":"Disease","text":["pulmonary hypertension"],"offsets":[[46,68]],"normalized":[{"db_name":"MESH","db_id":"D006976"}]},{"id":"20627","type":"Chemical","text":["Fluoxetine"],"offsets":[[92,102]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"20628","type":"Chemical","text":["serotonin"],"offsets":[[118,127]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"20629","type":"Chemical","text":["fluoxetine"],"offsets":[[227,237]],"normalized":[{"db_name":"MESH","db_id":"D005473"}]},{"id":"20630","type":"Disease","text":["pulmonary hypertension syndrome"],"offsets":[[297,328]],"normalized":[{"db_name":"MESH","db_id":"D006976"}]},{"id":"20631","type":"Disease","text":["pulmonary 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{"id":"20767","document_id":"17344330","passages":[{"id":"20768","type":"title","text":["Syncope and QT prolongation among patients treated with methadone for heroin dependence in the city of Copenhagen."],"offsets":[[0,114]]},{"id":"20769","type":"abstract","text":["BACKGROUND: Methadone is prescribed to heroin addicts to decrease illicit opioid use. Prolongation of the QT interval in the ECG of patients with torsade de pointes (TdP) has been reported in methadone users. As heroin addicts sometimes faint while using illicit drugs, doctors might attribute too many episodes of syncope to illicit drug use and thereby underestimate the incidence of TdP in this special population, and the high mortality in this population may, in part, be caused by the proarrhythmic effect of methadone. METHODS: In this cross-sectional study interview, ECGs and blood samples were collected in a population of adult heroin addicts treated with methadone or buprenorphine on a daily basis. Of the patients at the Drug Addiction Service in the municipal of Copenhagen, 450 (approximately 52%) were included. The QT interval was estimated from 12 lead ECGs. All participants were interviewed about any experience of syncope. The association between opioid dose and QT, and methadone dose and reporting of syncope was assessed using multivariate linear regression and logistic regression, respectively. RESULTS: Methadone dose was associated with longer QT interval of 0.140 ms\/mg (p = 0.002). No association between buprenorphine and QTc was found. Among the subjects treated with methadone, 28% men and 32% women had prolonged QTc interval. None of the subjects treated with buprenorphine had QTc interval >0.440 s((1\/2)). A 50 mg higher methadone dose was associated with a 1.2 (95% CI 1.1 to 1.4) times higher odds for syncope. CONCLUSIONS: Methadone is associated with QT prolongation and higher reporting of syncope in a population of heroin addicts."],"offsets":[[115,1790]]}],"entities":[{"id":"20770","type":"Disease","text":["Syncope"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D013575"}]},{"id":"20771","type":"Disease","text":["QT prolongation"],"offsets":[[12,27]],"normalized":[{"db_name":"MESH","db_id":"D008133"}]},{"id":"20772","type":"Chemical","text":["methadone"],"offsets":[[56,65]],"normalized":[{"db_name":"MESH","db_id":"D008691"}]},{"id":"20773","type":"Chemical","text":["heroin"],"offsets":[[70,76]],"normalized":[{"db_name":"MESH","db_id":"D003932"}]},{"id":"20774","type":"Chemical","text":["Methadone"],"offsets":[[127,136]],"normalized":[{"db_name":"MESH","db_id":"D008691"}]},{"id":"20775","type":"Chemical","text":["heroin"],"offsets":[[154,160]],"normalized":[{"db_name":"MESH","db_id":"D003932"}]},{"id":"20776","type":"Disease","text":["torsade de 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{"id":"20890","document_id":"16826348","passages":[{"id":"20891","type":"title","text":["Peripheral neuropathy caused by high-dose cytosine arabinoside treatment in a patient with acute myeloid leukemia."],"offsets":[[0,114]]},{"id":"20892","type":"abstract","text":["The central nervous system toxicity of high-dose cytosine arabinoside is well recognized, but the toxicity of cytosine arabinoside in the peripheral nervous system has been infrequently reported. A 49-year-old Japanese man was diagnosed with acute myeloid leukemia. After he achieved complete remission, he received high-dose cytosine arabinoside treatment (2 g\/m2 twice a day for 5 days; total, 20 g\/m2) as consolidation therapy. The first course of high-dose cytosine arabinoside resulted in no unusual symptoms, but on day 21 of the second course of treatment, the patient complained of numbness in his right foot. Electromyogram and nerve-conduction studies showed peripheral neuropathy in both peroneal nerves. This neuropathy was gradually resolving; however, after the patient received allogeneic bone marrow transplantation, the symptoms worsened, with the development of graft-versus-host disease, and the symptoms subsequently responded to methylprednisolone. Although the mechanisms of peripheral neuropathy are still unclear, high-dose cytosine arabinoside is a therapy that is potentially toxic to the peripheral nervous system, and auto\/alloimmunity may play an important role in these mechanisms."],"offsets":[[115,1326]]}],"entities":[{"id":"20893","type":"Disease","text":["Peripheral neuropathy"],"offsets":[[0,21]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"20894","type":"Chemical","text":["cytosine arabinoside"],"offsets":[[42,62]],"normalized":[{"db_name":"MESH","db_id":"D003561"}]},{"id":"20895","type":"Disease","text":["acute myeloid leukemia"],"offsets":[[91,113]],"normalized":[{"db_name":"MESH","db_id":"D015470"}]},{"id":"20896","type":"Disease","text":["toxicity"],"offsets":[[142,150]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"20897","type":"Chemical","text":["cytosine arabinoside"],"offsets":[[164,184]],"normalized":[{"db_name":"MESH","db_id":"D003561"}]},{"id":"20898","type":"Disease","text":["toxicity"],"offsets":[[213,221]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"20899","type":"Chemical","text":["cytosine arabinoside"],"offsets":[[225,245]],"normalized":[{"db_name":"MESH","db_id":"D003561"}]},{"id":"20900","type":"Disease","text":["acute myeloid leukemia"],"offsets":[[357,379]],"normalized":[{"db_name":"MESH","db_id":"D015470"}]},{"id":"20901","type":"Chemical","text":["cytosine arabinoside"],"offsets":[[441,461]],"normalized":[{"db_name":"MESH","db_id":"D003561"}]},{"id":"20902","type":"Chemical","text":["cytosine arabinoside"],"offsets":[[576,596]],"normalized":[{"db_name":"MESH","db_id":"D003561"}]},{"id":"20903","type":"Disease","text":["numbness"],"offsets":[[705,713]],"normalized":[{"db_name":"MESH","db_id":"D006987"}]},{"id":"20904","type":"Disease","text":["peripheral neuropathy"],"offsets":[[784,805]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"20905","type":"Disease","text":["neuropathy"],"offsets":[[836,846]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"20906","type":"Disease","text":["graft-versus-host disease"],"offsets":[[995,1020]],"normalized":[{"db_name":"MESH","db_id":"D006086"}]},{"id":"20907","type":"Chemical","text":["methylprednisolone"],"offsets":[[1065,1083]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"20908","type":"Disease","text":["peripheral neuropathy"],"offsets":[[1112,1133]],"normalized":[{"db_name":"MESH","db_id":"D010523"}]},{"id":"20909","type":"Chemical","text":["cytosine arabinoside"],"offsets":[[1163,1183]],"normalized":[{"db_name":"MESH","db_id":"D003561"}]}],"events":[],"coreferences":[],"relations":[{"id":"20910","type":"CID","arg1_id":"20894","arg2_id":"20893","normalized":[]},{"id":"20911","type":"CID","arg1_id":"20894","arg2_id":"20904","normalized":[]},{"id":"20912","type":"CID","arg1_id":"20894","arg2_id":"20908","normalized":[]},{"id":"20913","type":"CID","arg1_id":"20897","arg2_id":"20893","normalized":[]},{"id":"20914","type":"CID","arg1_id":"20897","arg2_id":"20904","normalized":[]},{"id":"20915","type":"CID","arg1_id":"20897","arg2_id":"20908","normalized":[]},{"id":"20916","type":"CID","arg1_id":"20899","arg2_id":"20893","normalized":[]},{"id":"20917","type":"CID","arg1_id":"20899","arg2_id":"20904","normalized":[]},{"id":"20918","type":"CID","arg1_id":"20899","arg2_id":"20908","normalized":[]},{"id":"20919","type":"CID","arg1_id":"20901","arg2_id":"20893","normalized":[]},{"id":"20920","type":"CID","arg1_id":"20901","arg2_id":"20904","normalized":[]},{"id":"20921","type":"CID","arg1_id":"20901","arg2_id":"20908","normalized":[]},{"id":"20922","type":"CID","arg1_id":"20902","arg2_id":"20893","normalized":[]},{"id":"20923","type":"CID","arg1_id":"20902","arg2_id":"20904","normalized":[]},{"id":"20924","type":"CID","arg1_id":"20902","arg2_id":"20908","normalized":[]},{"id":"20925","type":"CID","arg1_id":"20909","arg2_id":"20893","normalized":[]},{"id":"20926","type":"CID","arg1_id":"20909","arg2_id":"20904","normalized":[]},{"id":"20927","type":"CID","arg1_id":"20909","arg2_id":"20908","normalized":[]}]}
{"id":"20928","document_id":"16820346","passages":[{"id":"20929","type":"title","text":["Atorvastatin prevented and reversed dexamethasone-induced hypertension in the rat."],"offsets":[[0,82]]},{"id":"20930","type":"abstract","text":["To assess the antioxidant effects of atorvastatin (atorva) on dexamethasone (dex)-induced hypertension, 60 male Sprague-Dawley rats were treated with atorva 30 mg\/kg\/day or tap water for 15 days. Dex increased systolic blood pressure (SBP) from 109 +\/- 1.8 to 135 +\/- 0.6 mmHg and plasma superoxide (5711 +\/- 284.9 saline, 7931 +\/- 392.8 U\/ml dex, P < 0.001). In this prevention study, SBP in the atorva + dex group was increased from 115 +\/- 0.4 to 124 +\/- 1.5 mmHg, but this was significantly lower than in the dex-only group (P' < 0.05). Atorva reversed dex-induced hypertension (129 +\/- 0.6 mmHg, vs. 135 +\/- 0.6 mmHg P' < 0.05) and decreased plasma superoxide (7931 +\/- 392.8 dex, 1187 +\/- 441.2 atorva + dex, P < 0.0001). Plasma nitrate\/nitrite (NOx) was decreased in dex-treated rats compared to saline-treated rats (11.2 +\/- 1.08 microm, 15.3 +\/- 1.17 microm, respectively, P < 0.05). Atorva affected neither plasma NOx nor thymus weight. Thus, atorvastatin prevented and reversed dexamethasone-induced hypertension in the rat."],"offsets":[[83,1118]]}],"entities":[{"id":"20931","type":"Chemical","text":["Atorvastatin"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"C065179"}]},{"id":"20932","type":"Chemical","text":["dexamethasone"],"offsets":[[36,49]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"20933","type":"Disease","text":["hypertension"],"offsets":[[58,70]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"20934","type":"Chemical","text":["atorvastatin"],"offsets":[[120,132]],"normalized":[{"db_name":"MESH","db_id":"C065179"}]},{"id":"20935","type":"Chemical","text":["atorva"],"offsets":[[134,140]],"normalized":[{"db_name":"MESH","db_id":"C065179"}]},{"id":"20936","type":"Chemical","text":["dexamethasone"],"offsets":[[145,158]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"20937","type":"Chemical","text":["dex"],"offsets":[[160,163]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"20938","type":"Disease","text":["hypertension"],"offsets":[[173,185]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"20939","type":"Chemical","text":["atorva"],"offsets":[[233,239]],"normalized":[{"db_name":"MESH","db_id":"C065179"}]},{"id":"20940","type":"Chemical","text":["Dex"],"offsets":[[279,282]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"20941","type":"Chemical","text":["superoxide"],"offsets":[[371,381]],"normalized":[{"db_name":"MESH","db_id":"D013481"}]},{"id":"20942","type":"Chemical","text":["dex"],"offsets":[[426,429]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"20943","type":"Chemical","text":["atorva"],"offsets":[[480,486]],"normalized":[{"db_name":"MESH","db_id":"C065179"}]},{"id":"20944","type":"Chemical","text":["dex"],"offsets":[[489,492]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"20945","type":"Chemical","text":["dex"],"offsets":[[596,599]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"20946","type":"Chemical","text":["Atorva"],"offsets":[[624,630]],"normalized":[{"db_name":"MESH","db_id":"C065179"}]},{"id":"20947","type":"Chemical","text":["dex"],"offsets":[[640,643]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"20948","type":"Disease","text":["hypertension"],"offsets":[[652,664]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"20949","type":"Chemical","text":["superoxide"],"offsets":[[737,747]],"normalized":[{"db_name":"MESH","db_id":"D013481"}]},{"id":"20950","type":"Chemical","text":["dex"],"offsets":[[764,767]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"20951","type":"Chemical","text":["atorva"],"offsets":[[784,790]],"normalized":[{"db_name":"MESH","db_id":"C065179"}]},{"id":"20952","type":"Chemical","text":["dex"],"offsets":[[793,796]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"20953","type":"Chemical","text":["nitrate"],"offsets":[[818,825]],"normalized":[{"db_name":"MESH","db_id":"D009566"}]},{"id":"20954","type":"Chemical","text":["nitrite"],"offsets":[[826,833]],"normalized":[{"db_name":"MESH","db_id":"D009573"}]},{"id":"20955","type":"Chemical","text":["dex"],"offsets":[[857,860]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"20956","type":"Chemical","text":["Atorva"],"offsets":[[976,982]],"normalized":[{"db_name":"MESH","db_id":"C065179"}]},{"id":"20957","type":"Chemical","text":["atorvastatin"],"offsets":[[1036,1048]],"normalized":[{"db_name":"MESH","db_id":"C065179"}]},{"id":"20958","type":"Chemical","text":["dexamethasone"],"offsets":[[1072,1085]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"20959","type":"Disease","text":["hypertension"],"offsets":[[1094,1106]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]}],"events":[],"coreferences":[],"relations":[{"id":"20960","type":"CID","arg1_id":"20932","arg2_id":"20933","normalized":[]},{"id":"20961","type":"CID","arg1_id":"20932","arg2_id":"20938","normalized":[]},{"id":"20962","type":"CID","arg1_id":"20932","arg2_id":"20948","normalized":[]},{"id":"20963","type":"CID","arg1_id":"20932","arg2_id":"20959","normalized":[]},{"id":"20964","type":"CID","arg1_id":"20936","arg2_id":"20933","normalized":[]},{"id":"20965","type":"CID","arg1_id":"20936","arg2_id":"20938","normalized":[]},{"id":"20966","type":"CID","arg1_id":"20936","arg2_id":"20948","normalized":[]},{"id":"20967","type":"CID","arg1_id":"20936","arg2_id":"20959","normalized":[]},{"id":"20968","type":"CID","arg1_id":"20937","arg2_id":"20933","normalized":[]},{"id":"20969","type":"CID","arg1_id":"20937","arg2_id":"20938","normalized":[]},{"id":"20970","type":"CID","arg1_id":"20937","arg2_id":"20948","normalized":[]},{"id":"20971","type":"CID","arg1_id":"20937","arg2_id":"20959","normalized":[]},{"id":"20972","type":"CID","arg1_id":"20940","arg2_id":"20933","normalized":[]},{"id":"20973","type":"CID","arg1_id":"20940","arg2_id":"20938","normalized":[]},{"id":"20974","type":"CID","arg1_id":"20940","arg2_id":"20948","normalized":[]},{"id":"20975","type":"CID","arg1_id":"20940","a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{"id":"21008","document_id":"15974569","passages":[{"id":"21009","type":"title","text":["Two prodrugs of potent and selective GluR5 kainate receptor antagonists actives in three animal models of pain."],"offsets":[[0,111]]},{"id":"21010","type":"abstract","text":["Amino acids 5 and 7, two potent and selective competitive GluR5 KA receptor antagonists, exhibited high GluR5 receptor affinity over other glutamate receptors. Their ester prodrugs 6 and 8 were orally active in three models of pain: reversal of formalin-induced paw licking, carrageenan-induced thermal hyperalgesia, and capsaicin-induced mechanical hyperalgesia."],"offsets":[[112,475]]}],"entities":[{"id":"21011","type":"Chemical","text":["kainate"],"offsets":[[43,50]],"normalized":[{"db_name":"MESH","db_id":"D007608"}]},{"id":"21012","type":"Disease","text":["pain"],"offsets":[[106,110]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"21013","type":"Chemical","text":["KA"],"offsets":[[176,178]],"normalized":[{"db_name":"MESH","db_id":"D007608"}]},{"id":"21014","type":"Chemical","text":["glutamate"],"offsets":[[251,260]],"normalized":[{"db_name":"MESH","db_id":"D018698"}]},{"id":"21015","type":"Disease","text":["pain"],"offsets":[[339,343]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"21016","type":"Chemical","text":["formalin"],"offsets":[[357,365]],"normalized":[{"db_name":"MESH","db_id":"D005557"}]},{"id":"21017","type":"Chemical","text":["carrageenan"],"offsets":[[387,398]],"normalized":[{"db_name":"MESH","db_id":"D002351"}]},{"id":"21018","type":"Disease","text":["thermal hyperalgesia"],"offsets":[[407,427]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"21019","type":"Chemical","text":["capsaicin"],"offsets":[[433,442]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"21020","type":"Disease","text":["mechanical hyperalgesia"],"offsets":[[451,474]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]}],"events":[],"coreferences":[],"relations":[{"id":"21021","type":"CID","arg1_id":"21017","arg2_id":"21018","normalized":[]},{"id":"21022","type":"CID","arg1_id":"21017","arg2_id":"21020","normalized":[]},{"id":"21023","type":"CID","arg1_id":"21019","arg2_id":"21018","normalized":[]},{"id":"21024","type":"CID","arg1_id":"21019","arg2_id":"21020","normalized":[]}]}
{"id":"21025","document_id":"11583940","passages":[{"id":"21026","type":"title","text":["Sirolimus and mycophenolate mofetil for calcineurin-free immunosuppression in renal transplant recipients."],"offsets":[[0,106]]},{"id":"21027","type":"abstract","text":["Calcineurin inhibitors, such as cyclosporine and tacrolimus, have been available for almost 20 years. Although these drugs are highly effective and represent the mainstay of transplant immunosuppression, they are associated with acute and chronic nephrotoxicity. Acute nephrotoxicity, which occurs in the early period after transplantation, leads to a higher rate of dialysis, and chronic nephrotoxicity may eventually result in graft loss. Acute and chronic nephrotoxicity is becoming more common as the use of marginal kidneys for transplantation increases. Two recently available immunosuppressive agents, mycophenolate mofetil and sirolimus (rapamycin), have no nephrotoxicity. The use of these drugs in combination with other agents has led to the development of new paradigms of immunosuppressive therapy. This paper reviews the results of clinical trials that have investigated these new approaches to immunosuppression in renal transplant recipients."],"offsets":[[107,1065]]}],"entities":[{"id":"21028","type":"Chemical","text":["Sirolimus"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"21029","type":"Chemical","text":["mycophenolate mofetil"],"offsets":[[14,35]],"normalized":[{"db_name":"MESH","db_id":"C063008"}]},{"id":"21030","type":"Chemical","text":["cyclosporine"],"offsets":[[139,151]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"21031","type":"Chemical","text":["tacrolimus"],"offsets":[[156,166]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"21032","type":"Disease","text":["nephrotoxicity"],"offsets":[[354,368]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"21033","type":"Disease","text":["nephrotoxicity"],"offsets":[[376,390]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"21034","type":"Disease","text":["nephrotoxicity"],"offsets":[[496,510]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"21035","type":"Disease","text":["nephrotoxicity"],"offsets":[[566,580]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"21036","type":"Chemical","text":["mycophenolate mofetil"],"offsets":[[716,737]],"normalized":[{"db_name":"MESH","db_id":"C063008"}]},{"id":"21037","type":"Chemical","text":["sirolimus"],"offsets":[[742,751]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"21038","type":"Chemical","text":["rapamycin"],"offsets":[[753,762]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"21039","type":"Disease","text":["nephrotoxicity"],"offsets":[[773,787]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]}],"events":[],"coreferences":[],"relations":[{"id":"21040","type":"CID","arg1_id":"21031","arg2_id":"21032","normalized":[]},{"id":"21041","type":"CID","arg1_id":"21031","arg2_id":"21033","normalized":[]},{"id":"21042","type":"CID","arg1_id":"21031","arg2_id":"21034","normalized":[]},{"id":"21043","type":"CID","arg1_id":"21031","arg2_id":"21035","normalized":[]},{"id":"21044","type":"CID","arg1_id":"21031","arg2_id":"21039","normalized":[]},{"id":"21045","type":"CID","arg1_id":"21030","arg2_id":"21032","normalized":[]},{"id":"21046","type":"CID","arg1_id":"21030","arg2_id":"21033","normalized":[]},{"id":"21047","type":"CID","arg1_id":"21030","arg2_id":"21034","normalized":[]},{"id":"21048","type":"CID","arg1_id":"21030","arg2_id":"21035","normalized":[]},{"id":"21049","type":"CID","arg1_id":"21030","arg2_id":"21039","normalized":[]}]}
{"id":"21050","document_id":"11245434","passages":[{"id":"21051","type":"title","text":["Erythropoietin restores the anemia-induced reduction in cyclophosphamide cytotoxicity in rat tumors."],"offsets":[[0,100]]},{"id":"21052","type":"abstract","text":["The aim of this study was to examine the impact of anemia prevention by recombinant human erythropoietin (rHuEPO) treatment on the cytotoxicity of cyclophosphamide in solid experimental tumors. Anemia was induced using a single dose of carboplatin (50 mg\/kg i.v.) resulting in a long-lasting reduction (30%) of the hemoglobin concentration. In a second group, the development of anemia was prevented by rHuEPO (1000 IU\/kg) administered s.c. three times\/week starting 7 days before carboplatin application. Four days after carboplatin treatment, tumors (DS-sarcoma of the rat) were implanted s.c. onto the hind food dorsum. Neither carboplatin nor rHuEPO treatment influenced tumor growth rate per se. When tumors were treated with a single dose of cyclophosphamide (60 mg\/kg i.p.) 5 days after implantation, a growth delay with a subsequent regrowth of the tumors was observed. In the anemia group, the growth delay was significantly shorter compared with nonanemic controls (13.3 days versus 8.6 days). In the group where anemia was prevented by rHuEPO treatment, growth delay was comparable with that of nonanemic controls (13.3 days). These results suggest that chemotherapy-induced anemia reduces cytotoxicity of cyclophosphamide in tumors, whereas correction of anemia by rHuEPO treatment (epoetin alpha) increases the sensitivity, probably as a result of an improved oxygen supply to tumor tissue."],"offsets":[[101,1504]]}],"entities":[{"id":"21053","type":"Disease","text":["anemia"],"offsets":[[28,34]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"21054","type":"Chemical","text":["cyclophosphamide"],"offsets":[[56,72]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"21055","type":"Disease","text":["cytotoxicity"],"offsets":[[73,85]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"21056","type":"Disease","text":["tumors"],"offsets":[[93,99]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"21057","type":"Disease","text":["anemia"],"offsets":[[152,158]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"21058","type":"Disease","text":["cytotoxicity"],"offsets":[[232,244]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"21059","type":"Chemical","text":["cyclophosphamide"],"offsets":[[248,264]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"21060","type":"Disease","text":["tumors"],"offsets":[[287,293]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"21061","type":"Disease","text":["Anemia"],"offsets":[[295,301]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"21062","type":"Chemical","text":["carboplatin"],"offsets":[[337,348]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"21063","type":"Disease","text":["anemia"],"offsets":[[480,486]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"21064","type":"Chemical","text":["carboplatin"],"offsets":[[582,593]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"21065","type":"Chemical","text":["carboplatin"],"offsets":[[623,634]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"21066","type":"Disease","text":["tumors"],"offsets":[[646,652]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"21067","type":"Disease","text":["sarcoma"],"offsets":[[657,664]],"normalized":[{"db_name":"MESH","db_id":"D012509"}]},{"id":"21068","type":"Chemical","text":["carboplatin"],"offsets":[[732,743]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"21069","type":"Disease","text":["tumor"],"offsets":[[776,781]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"21070","type":"Disease","text":["tumors"],"offsets":[[807,813]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"21071","type":"Chemical","text":["cyclophosphamide"],"offsets":[[849,865]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"21072","type":"Disease","text":["tumors"],"offsets":[[958,964]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"21073","type":"Disease","text":["anemia"],"offsets":[[986,992]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"21074","type":"Disease","text":["anemia"],"offsets":[[1124,1130]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"21075","type":"Disease","text":["anemia"],"offsets":[[1287,1293]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"21076","type":"Disease","text":["cytotoxicity"],"offsets":[[1302,1314]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"21077","type":"Chemical","text":["cyclophosphamide"],"offsets":[[1318,1334]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"21078","type":"Disease","text":["tumors"],"offsets":[[1338,1344]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"21079","type":"Disease","text":["anemia"],"offsets":[[1368,1374]],"normalized":[{"db_name":"MESH","db_id":"D000740"}]},{"id":"21080","type":"Chemical","text":["oxygen"],"offsets":[[1474,1480]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"21081","type":"Disease","text":["tumor"],"offsets":[[1491,1496]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]}],"events":[],"coreferences":[],"relations":[{"id":"21082","type":"CID","arg1_id":"21062","arg2_id":"21053","normalized":[]},{"id":"21083","type":"CID","arg1_id":"21062","arg2_id":"21057","normalized":[]},{"id":"21084","type":"CID","arg1_id":"21062","arg2_id":"21061","normalized":[]},{"id":"21085","type":"CID","arg1_id":"21062","arg2_id":"21063","normalized":[]},{"id":"21086","type":"CID","arg1_id":"21062","arg2_id":"21073","normalized":[]},{"id":"21087","type":"CID","arg1_id":"21062","arg2_id":"21074","normalized":[]},{"id":"21088","type":"CID","arg1_id":"21062","arg2_id":"21075","normalized":[]},{"id":"21089","type":"CID","arg1_id":"21062","arg2_id":"21079","normalized":[]},{"id":"21090","type":"CID","arg1_id":"21064","arg2_id":"21053","normalized":[]},{"id":"21091","type":"CID","arg1_id":"21064","arg2_id":"21057","normalized":[]},{"id":"21092","type":"CID","arg1_id":"21064","arg2_id":"21061","normalized":[]},{"id":"21093","type":"CID","arg1_id":"21064","arg2_id":"21063","normalized":[]},{"id":"21094","type":"CID","arg1_id":"21064","arg2_id":"21073","normalized":[]},{"id":"21095","type":"CID","arg1_id":"21064","arg2_id":"21074","normalized":[]},{"id":"21096","type":"CID","arg1_id":"21064","arg2_id":"21075","normalized":[]},{"id":"21097","type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{"id":"21114","document_id":"11243580","passages":[{"id":"21115","type":"title","text":["The role of nitrergic system in lidocaine-induced convulsion in the mouse."],"offsets":[[0,74]]},{"id":"21116","type":"abstract","text":["The effects of N-nitro-L-arginine-methyl ester (L-NAME) a nitric oxide (NO) synthase inhibitor and L-arginine, a NO precursor, were investigated on lidocaine-induced convulsions. In the first experiment, four groups of mice received physiological saline (0.9%), L-arginine (300 mg\/kg, i.p.), L-NAME (100 mg\/kg, i.p.) and diazepam (2 mg\/kg), respectively. Thirty minutes after these injections, all mice received lidocaine (50 mg\/kg, i.p.). In the second experiment, four groups of mice received similar treatment in the first experiment, and 30 min after these injections, all mice received a higher dose of lidocaine (80 mg\/kg). L-NAME (100 mg\/kg, i.p.) and diazepam (2 mg\/kg) significantly decreased the incidence of lidocaine (50 mg\/kg)-induced convulsions. In contrast, the L-arginine treatment increased the incidence of lidocaine (80 mg\/kg, i.p.)-induced convulsions significantly. These results may suggest that NO is a proconvulsant mediator in lidocaine-induced convulsions."],"offsets":[[75,1058]]}],"entities":[{"id":"21117","type":"Chemical","text":["lidocaine"],"offsets":[[32,41]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"21118","type":"Disease","text":["convulsion"],"offsets":[[50,60]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"21119","type":"Chemical","text":["N-nitro-L-arginine-methyl ester"],"offsets":[[90,121]],"normalized":[{"db_name":"MESH","db_id":"D019331"}]},{"id":"21120","type":"Chemical","text":["L-NAME"],"offsets":[[123,129]],"normalized":[{"db_name":"MESH","db_id":"D019331"}]},{"id":"21121","type":"Chemical","text":["nitric oxide"],"offsets":[[133,145]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"21122","type":"Chemical","text":["NO"],"offsets":[[147,149]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"21123","type":"Chemical","text":["L-arginine"],"offsets":[[174,184]],"normalized":[{"db_name":"MESH","db_id":"D001120"}]},{"id":"21124","type":"Chemical","text":["NO"],"offsets":[[188,190]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"21125","type":"Chemical","text":["lidocaine"],"offsets":[[223,232]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"21126","type":"Disease","text":["convulsions"],"offsets":[[241,252]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"21127","type":"Chemical","text":["L-arginine"],"offsets":[[337,347]],"normalized":[{"db_name":"MESH","db_id":"D001120"}]},{"id":"21128","type":"Chemical","text":["L-NAME"],"offsets":[[367,373]],"normalized":[{"db_name":"MESH","db_id":"D019331"}]},{"id":"21129","type":"Chemical","text":["diazepam"],"offsets":[[396,404]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"21130","type":"Chemical","text":["lidocaine"],"offsets":[[487,496]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"21131","type":"Chemical","text":["lidocaine"],"offsets":[[683,692]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"21132","type":"Chemical","text":["L-NAME"],"offsets":[[705,711]],"normalized":[{"db_name":"MESH","db_id":"D019331"}]},{"id":"21133","type":"Chemical","text":["diazepam"],"offsets":[[734,742]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"21134","type":"Chemical","text":["lidocaine"],"offsets":[[794,803]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"21135","type":"Disease","text":["convulsions"],"offsets":[[823,834]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"21136","type":"Chemical","text":["L-arginine"],"offsets":[[853,863]],"normalized":[{"db_name":"MESH","db_id":"D001120"}]},{"id":"21137","type":"Chemical","text":["lidocaine"],"offsets":[[901,910]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"21138","type":"Disease","text":["convulsions"],"offsets":[[936,947]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"21139","type":"Chemical","text":["NO"],"offsets":[[994,996]],"normalized":[{"db_name":"MESH","db_id":"D009569"}]},{"id":"21140","type":"Chemical","text":["lidocaine"],"offsets":[[1028,1037]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"21141","type":"Disease","text":["convulsions"],"offsets":[[1046,1057]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]}],"events":[],"coreferences":[],"relations":[{"id":"21142","type":"CID","arg1_id":"21117","arg2_id":"21118","normalized":[]},{"id":"21143","type":"CID","arg1_id":"21117","arg2_id":"21126","normalized":[]},{"id":"21144","type":"CID","arg1_id":"21117","arg2_id":"21135","normalized":[]},{"id":"21145","type":"CID","arg1_id":"21117","arg2_id":"21138","normalized":[]},{"id":"21146","type":"CID","arg1_id":"21117","arg2_id":"21141","normalized":[]},{"id":"21147","type":"CID","arg1_id":"21125","arg2_id":"21118","normalized":[]},{"id":"21148","type":"CID","arg1_id":"21125","arg2_id":"21126","normalized":[]},{"id":"21149","type":"CID","arg1_id":"21125","arg2_id":"21135","normalized":[]},{"id":"21150","type":"CID","arg1_id":"21125","arg2_id":"21138","normalized":[]},{"id":"21151","type":"CID","arg1_id":"21125","arg2_id":"21141","normalized":[]},{"id":"21152","type":"CID","arg1_id":"21130","arg2_id":"21118","normalized":[]},{"id":"21153","type":"CID","arg1_id":"21130","arg2_id":"21126","normalized":[]},{"id":"21154","type":"CID","arg1_id":"21130","arg2_id":"21135","normalized":[]},{"id":"21155","type":"CID","arg1_id":"21130","arg2_id":"21138","normalized":[]},{"id":"21156","type":"CID","arg1_id":"21130","arg2_id":"21141","normalized":[]},{"id":"21157","type":"CID","arg1_id":"21131","arg2_id":"21118","normalized":[]},{"id":"21158","type":"CID","arg1_id":"21131","arg2_id":"21126","normalized":[]},{"id":"21159","type":"CID","arg1_id":"21131","arg2_id":"21135","normalized":[]},{"id":"21160","type":"CID","arg1_id":"21131","arg2_id":"21138","normalized":[]},{"id":"21161","type":"CID","arg1_id":"21131","arg2_id":"21141","normalized":[]},{"id":"21162","type":"CID","arg1_id":"21134","arg2_id":"21118","normalized":[]},{"id":"21163","type":"CID","arg1_id":"21134","arg2_id":"21126","normalized":[]},{"id":"21164","type":"CID","arg1_id":"21134","arg2_id":"21135","normalized":[]},{"id":"21165","type":"CID","arg1_id":"21134","arg2_id":"21138","normalized":[]},{"id":"21166","type":"CID","arg1_id":"21134","arg2_id":"21141","normalized":[]},{"id":"21167","type":"CID","arg1_id":"21137","arg2_id":"21118","normalized":[]},{"id":"21168","type":"CID","arg1_id":"21137","arg2_id":"21126","normalized":[]},{"id":"21169","type":"CID","arg1_id":"21137","arg2_id":"21135","normalized":[]},{"id":"21170","type":"CID","arg1_id":"21137","arg2_id":"21138","normalized":[]},{"id":"21171","type":"CID","arg1_id":"21137","arg2_id":"21141","normalized":[]},{"id":"21172","type":"CID","arg1_id":"21140","arg2_id":"21118","normalized":[]},{"id":"21173","type":"CID","arg1_id":"21140","arg2_id":"21126","normalized":[]},{"id":"21174","type":"CID","arg1_id":"21140","arg2_id":"21135","normalized":[]},{"id":"21175","type":"CID","arg1_id":"21140","arg2_id":"21138","normalized":[]},{"id":"21176","type":"CID","arg1_id":"21140","arg2_id":"21141","normalized":[]}]}
{"id":"21177","document_id":"11079278","passages":[{"id":"21178","type":"title","text":["Effect of intravenous metoprolol or intravenous metoprolol plus glucagon on dobutamine-induced myocardial ischemia."],"offsets":[[0,115]]},{"id":"21179","type":"abstract","text":["STUDY OBJECTIVE: To determine the effect of metoprolol on dobutamine stress testing with technetium-99m sestamibi single-photon emission computed tomography imaging and ST-segment monitoring, and to assess the impact of intravenous glucagon on metoprolol's effects. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Community hospital. PATIENTS: Twenty-two patients with known reversible perfusion defects. INTERVENTION: Patients underwent dobutamine stress tests per standard protocol. Before dobutamine was begun, no therapy was given during the first visit, and patients were randomized on subsequent visits to receive metoprolol or metoprolol plus glucagon 1 mg. Metoprolol was dosed to achieve a resting predobutamine heart rate below 65 beats\/minute or a total intravenous dose of 20 mg. MEASUREMENTS AND MAIN RESULTS: Metoprolol reduced maximum heart rate 31%, summed stress scores 29%, and summed difference scores 43% versus control. Metoprolol plus glucagon also reduced the maximum heart rate 29% versus control. Summed stress and summed difference scores were not significantly reduced, although they were 18% and 30% lower, respectively, than control. No significant differences were found in any parameter between metoprolol and metoprolol-glucagon. CONCLUSION: During dobutamine stress testing, metoprolol attenuates or eliminates evidence of myocardial ischemia. Glucagon 1 mg, although somewhat effective, does not correct this effect to the extent that it can be administered clinically."],"offsets":[[116,1640]]}],"entities":[{"id":"21180","type":"Chemical","text":["metoprolol"],"offsets":[[22,32]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"21181","type":"Chemical","text":["metoprolol"],"offsets":[[48,58]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"21182","type":"Chemical","text":["dobutamine"],"offsets":[[76,86]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"21183","type":"Disease","text":["myocardial ischemia"],"offsets":[[95,114]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]},{"id":"21184","type":"Chemical","text":["metoprolol"],"offsets":[[160,170]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"21185","type":"Chemical","text":["dobutamine"],"offsets":[[174,184]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"21186","type":"Chemical","text":["technetium-99m sestamibi"],"offsets":[[205,229]],"normalized":[{"db_name":"MESH","db_id":"D017256"}]},{"id":"21187","type":"Chemical","text":["metoprolol"],"offsets":[[360,370]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"21188","type":"Chemical","text":["dobutamine"],"offsets":[[575,585]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"21189","type":"Chemical","text":["dobutamine"],"offsets":[[629,639]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"21190","type":"Chemical","text":["metoprolol"],"offsets":[[757,767]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"21191","type":"Chemical","text":["metoprolol"],"offsets":[[771,781]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"21192","type":"Chemical","text":["Metoprolol"],"offsets":[[802,812]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"21193","type":"Chemical","text":["predobutamine"],"offsets":[[844,857]],"normalized":[]},{"id":"21194","type":"Chemical","text":["Metoprolol"],"offsets":[[960,970]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"21195","type":"Chemical","text":["Metoprolol"],"offsets":[[1078,1088]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"21196","type":"Chemical","text":["metoprolol"],"offsets":[[1363,1373]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"21197","type":"Chemical","text":["metoprolol"],"offsets":[[1378,1388]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"21198","type":"Chemical","text":["dobutamine"],"offsets":[[1418,1428]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"21199","type":"Chemical","text":["metoprolol"],"offsets":[[1445,1455]],"normalized":[{"db_name":"MESH","db_id":"D008790"}]},{"id":"21200","type":"Disease","text":["myocardial ischemia"],"offsets":[[1493,1512]],"normalized":[{"db_name":"MESH","db_id":"D017202"}]}],"events":[],"coreferences":[],"relations":[{"id":"21201","type":"CID","arg1_id":"21182","arg2_id":"21183","normalized":[]},{"id":"21202","type":"CID","arg1_id":"21182","arg2_id":"21200","normalized":[]},{"id":"21203","type":"CID","arg1_id":"21185","arg2_id":"21183","normalized":[]},{"id":"21204","type":"CID","arg1_id":"21185","arg2_id":"21200","normalized":[]},{"id":"21205","type":"CID","arg1_id":"21188","arg2_id":"21183","normalized":[]},{"id":"21206","type":"CID","arg1_id":"21188","arg2_id":"21200","normalized":[]},{"id":"21207","type":"CID","arg1_id":"21189","arg2_id":"21183","normalized":[]},{"id":"21208","type":"CID","arg1_id":"21189","arg2_id":"21200","normalized":[]},{"id":"21209","type":"CID","arg1_id":"21198","arg2_id":"21183","normalized":[]},{"id":"21210","type":"CID","arg1_id":"21198","arg2_id":"21200","normalized":[]}]}
{"id":"21211","document_id":"10910842","passages":[{"id":"21212","type":"title","text":["Prednisolone-induced muscle dysfunction is caused more by atrophy than by altered acetylcholine receptor expression."],"offsets":[[0,116]]},{"id":"21213","type":"abstract","text":["Large doses of glucocorticoids can alter muscle physiology and susceptibility to neuromuscular blocking drugs by mechanisms not clearly understood. We investigated the effects of moderate and large doses of prednisolone on muscle function and pharmacology, and their relationship to changes in muscle size and acetylcholine receptor (AChR) expression. With institutional approval, 35 Sprague-Dawley rats were randomly allocated to receive daily subcutaneous doses of 10 mg\/kg prednisolone (P10 group), 100 mg\/kg prednisolone (P100 group), or an equal volume of saline (S group) for 7 days. A fourth group of rats was pair fed (food restricted) with the P100 rats for 7 days (FR group). On Day 8, the nerve-evoked peak twitch tensions, tetanic tensions, and fatigability, and the dose-response curves of d-tubocurarine in the tibialis cranialis muscle were measured in vivo and related to muscle mass or expression of AChRs. Rate of body weight gain was depressed in the P100, FR, and P10 groups compared with the S group. Tibialis muscle mass was smaller in the P100 group than in the P10 or S groups. The evoked peak twitch and tetanic tensions were less in the P100 group than in the P10 or S groups, however, tension per milligram of muscle mass was greater in the P100 group than in the S group. The 50% effective dose of d-tubocurarine (microg\/kg) in the tibialis muscle was smaller in the P10 (33.6 +\/- 5.4) than in the S (61.9 +\/- 5.0) or the P100 (71.3 +\/- 9.6) groups. AChR expression was less in the P10 group than in the S group. The evoked tensions correlated with muscle mass (r(2) = 0.32, P < 0.001), however, not with expression of AChR. The 50% effective dose of d-tubocurarine did not correlate with muscle mass or AChR expression. Our results suggest that the neuromuscular dysfunction after prednisolone is dose-dependent, and derives primarily from muscle atrophy and derives less so from changes in AChR expression. IMPLICATIONS: The mechanisms by which chronic glucocorticoid therapy alters neuromuscular physiology and pharmacology are unclear. We suggest that the observed effects are dose-dependent and derive primarily from muscle atrophy and derive less from changes in acetylcholine receptor expression."],"offsets":[[117,2348]]}],"entities":[{"id":"21214","type":"Chemical","text":["Prednisolone"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D011239"}]},{"id":"21215","type":"Disease","text":["muscle dysfunction"],"offsets":[[21,39]],"normalized":[{"db_name":"MESH","db_id":"D018908"}]},{"id":"21216","type":"Disease","text":["atrophy"],"offsets":[[58,65]],"normalized":[{"db_name":"MESH","db_id":"D001284"}]},{"id":"21217","type":"Chemical","text":["acetylcholine"],"offsets":[[82,95]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"21218","type":"Chemical","text":["prednisolone"],"offsets":[[324,336]],"normalized":[{"db_name":"MESH","db_id":"D011239"}]},{"id":"21219","type":"Chemical","text":["acetylcholine"],"offsets":[[427,440]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]},{"id":"21220","type":"Chemical","text":["prednisolone"],"offsets":[[593,605]],"normalized":[{"db_name":"MESH","db_id":"D011239"}]},{"id":"21221","type":"Chemical","text":["prednisolone"],"offsets":[[629,641]],"normalized":[{"db_name":"MESH","db_id":"D011239"}]},{"id":"21222","type":"Disease","text":["tetanic"],"offsets":[[852,859]],"normalized":[{"db_name":"MESH","db_id":"D013746"}]},{"id":"21223","type":"Chemical","text":["d-tubocurarine"],"offsets":[[920,934]],"normalized":[{"db_name":"MESH","db_id":"D014403"}]},{"id":"21224","type":"Disease","text":["tetanic"],"offsets":[[1246,1253]],"normalized":[{"db_name":"MESH","db_id":"D013746"}]},{"id":"21225","type":"Chemical","text":["d-tubocurarine"],"offsets":[[1443,1457]],"normalized":[{"db_name":"MESH","db_id":"D014403"}]},{"id":"21226","type":"Chemical","text":["d-tubocurarine"],"offsets":[[1796,1810]],"normalized":[{"db_name":"MESH","db_id":"D014403"}]},{"id":"21227","type":"Disease","text":["neuromuscular dysfunction"],"offsets":[[1895,1920]],"normalized":[{"db_name":"MESH","db_id":"D009468"}]},{"id":"21228","type":"Chemical","text":["prednisolone"],"offsets":[[1927,1939]],"normalized":[{"db_name":"MESH","db_id":"D011239"}]},{"id":"21229","type":"Disease","text":["muscle atrophy"],"offsets":[[1986,2000]],"normalized":[{"db_name":"MESH","db_id":"D009133"}]},{"id":"21230","type":"Disease","text":["muscle atrophy"],"offsets":[[2267,2281]],"normalized":[{"db_name":"MESH","db_id":"D009133"}]},{"id":"21231","type":"Chemical","text":["acetylcholine"],"offsets":[[2314,2327]],"normalized":[{"db_name":"MESH","db_id":"D000109"}]}],"events":[],"coreferences":[],"relations":[{"id":"21232","type":"CID","arg1_id":"21214","arg2_id":"21215","normalized":[]},{"id":"21233","type":"CID","arg1_id":"21218","arg2_id":"21215","normalized":[]},{"id":"21234","type":"CID","arg1_id":"21220","arg2_id":"21215","normalized":[]},{"id":"21235","type":"CID","arg1_id":"21221","arg2_id":"21215","normalized":[]},{"id":"21236","type":"CID","arg1_id":"21228","arg2_id":"21215","normalized":[]},{"id":"21237","type":"CID","arg1_id":"21214","arg2_id":"21229","normalized":[]},{"id":"21238","type":"CID","arg1_id":"21214","arg2_id":"21230","normalized":[]},{"id":"21239","type":"CID","arg1_id":"21218","arg2_id":"21229","normalized":[]},{"id":"21240","type":"CID","arg1_id":"21218","arg2_id":"21230","normalized":[]},{"id":"21241","type":"CID","arg1_id":"21220","arg2_id":"21229","normalized":[]},{"id":"21242","type":"CID","arg1_id":"21220","arg2_id":"21230","normalized":[]},{"id":"21243","type":"CID","arg1_id":"21221","arg2_id":"21229","normalized":[]},{"id":"21244","type":"CID","arg1_id":"21221","arg2_id":"21230","normalized":[]},{"id":"21245","type":"CID","arg1_id":"21228","arg2_id":"21229","normalized":[]},{"id":"21246","type":"CID","arg1_id":"21228","arg2_id":"21230","normalized":[]}]}
{"id":"21247","document_id":"10533019","passages":[{"id":"21248","type":"title","text":["Rapid reversal of life-threatening diltiazem-induced tetany with calcium chloride."],"offsets":[[0,82]]},{"id":"21249","type":"abstract","text":["We describe a patient who developed tetany with sudden respiratory arrest after the infusion of intravenous diltiazem. The administration of calcium chloride rapidly resolved the patient's tetany with prompt recovery of respiratory function, averting the need for more aggressive airway management and ventilatory support. The emergency physician should be aware that life-threatening tetany may accompany the administration of intravenous diltiazem and that calcium chloride may be a rapid and effective remedy."],"offsets":[[83,595]]}],"entities":[{"id":"21250","type":"Chemical","text":["diltiazem"],"offsets":[[35,44]],"normalized":[{"db_name":"MESH","db_id":"D004110"}]},{"id":"21251","type":"Disease","text":["tetany"],"offsets":[[53,59]],"normalized":[{"db_name":"MESH","db_id":"D013746"}]},{"id":"21252","type":"Chemical","text":["calcium chloride"],"offsets":[[65,81]],"normalized":[{"db_name":"MESH","db_id":"D002122"}]},{"id":"21253","type":"Disease","text":["tetany"],"offsets":[[119,125]],"normalized":[{"db_name":"MESH","db_id":"D013746"}]},{"id":"21254","type":"Disease","text":["respiratory arrest"],"offsets":[[138,156]],"normalized":[{"db_name":"MESH","db_id":"D012131"}]},{"id":"21255","type":"Chemical","text":["diltiazem"],"offsets":[[191,200]],"normalized":[{"db_name":"MESH","db_id":"D004110"}]},{"id":"21256","type":"Chemical","text":["calcium chloride"],"offsets":[[224,240]],"normalized":[{"db_name":"MESH","db_id":"D002122"}]},{"id":"21257","type":"Disease","text":["tetany"],"offsets":[[272,278]],"normalized":[{"db_name":"MESH","db_id":"D013746"}]},{"id":"21258","type":"Disease","text":["tetany"],"offsets":[[468,474]],"normalized":[{"db_name":"MESH","db_id":"D013746"}]},{"id":"21259","type":"Chemical","text":["diltiazem"],"offsets":[[523,532]],"normalized":[{"db_name":"MESH","db_id":"D004110"}]},{"id":"21260","type":"Chemical","text":["calcium chloride"],"offsets":[[542,558]],"normalized":[{"db_name":"MESH","db_id":"D002122"}]}],"events":[],"coreferences":[],"relations":[{"id":"21261","type":"CID","arg1_id":"21250","arg2_id":"21251","normalized":[]},{"id":"21262","type":"CID","arg1_id":"21250","arg2_id":"21253","normalized":[]},{"id":"21263","type":"CID","arg1_id":"21250","arg2_id":"21257","normalized":[]},{"id":"21264","type":"CID","arg1_id":"21250","arg2_id":"21258","normalized":[]},{"id":"21265","type":"CID","arg1_id":"21255","arg2_id":"21251","normalized":[]},{"id":"21266","type":"CID","arg1_id":"21255","arg2_id":"21253","normalized":[]},{"id":"21267","type":"CID","arg1_id":"21255","arg2_id":"21257","normalized":[]},{"id":"21268","type":"CID","arg1_id":"21255","arg2_id":"21258","normalized":[]},{"id":"21269","type":"CID","arg1_id":"21259","arg2_id":"21251","normalized":[]},{"id":"21270","type":"CID","arg1_id":"21259","arg2_id":"21253","normalized":[]},{"id":"21271","type":"CID","arg1_id":"21259","arg2_id":"21257","normalized":[]},{"id":"21272","type":"CID","arg1_id":"21259","arg2_id":"21258","normalized":[]}]}
{"id":"21273","document_id":"10414674","passages":[{"id":"21274","type":"title","text":["Effects of nonsteroidal anti-inflammatory drugs on hemostasis in patients with aneurysmal subarachnoid hemorrhage."],"offsets":[[0,114]]},{"id":"21275","type":"abstract","text":["Platelet function is impaired by nonsteroidal anti-inflammatory drugs (NSAIDs) with prominent anti-inflammatory properties. Their safety in patients undergoing intracranial surgery is under debate. Patients with aneurysmal subarachnoid hemorrhage (SAH) were randomized to receive either ketoprofen, 100 mg, three times a day (ketoprofen group, n = 9) or a weak NSAID, acetaminophen, 1 g, three times a day (acetaminophen group, n = 9) starting immediately after the diagnosis of aneurysmal SAH. Treatment was continued for 3 days postoperatively. Test blood samples were taken before treatment and surgery as well as on the first, third, and fifth postoperative mornings. Maximal platelet aggregation induced by 6 microM of adenosine diphosphate decreased after administration of ketoprofen. Aggregation was lower (P < .05) in the ketoprofen group than in the acetaminophen group just before surgery and on the third postoperative day. In contrast, maximal platelet aggregation increased in the acetaminophen group on the third postoperative day as compared with the pretreatment platelet aggregation results (P < .05). One patient in the ketoprofen group developed a postoperative intracranial hematoma. Coagulation (prothrombin time [PT], activated partial thromboplastin time [APPT], fibrinogen concentration, and antithrombin III [AT III]) was comparable between the two groups. Ketoprofen but not acetaminophen impaired platelet function in patients with SAH. If ketoprofen is used before surgery on cerebral artery aneurysms, it may pose an additional risk factor for hemorrhage."],"offsets":[[115,1700]]}],"entities":[{"id":"21276","type":"Disease","text":["aneurysmal subarachnoid hemorrhage"],"offsets":[[79,113]],"normalized":[{"db_name":"MESH","db_id":"D013345"}]},{"id":"21277","type":"Disease","text":["aneurysmal subarachnoid hemorrhage"],"offsets":[[327,361]],"normalized":[{"db_name":"MESH","db_id":"D013345"}]},{"id":"21278","type":"Disease","text":["SAH"],"offsets":[[363,366]],"normalized":[{"db_name":"MESH","db_id":"D013345"}]},{"id":"21279","type":"Chemical","text":["ketoprofen"],"offsets":[[402,412]],"normalized":[{"db_name":"MESH","db_id":"D007660"}]},{"id":"21280","type":"Chemical","text":["ketoprofen"],"offsets":[[441,451]],"normalized":[{"db_name":"MESH","db_id":"D007660"}]},{"id":"21281","type":"Chemical","text":["acetaminophen"],"offsets":[[483,496]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"21282","type":"Chemical","text":["acetaminophen"],"offsets":[[522,535]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"21283","type":"Disease","text":["aneurysmal"],"offsets":[[594,604]],"normalized":[{"db_name":"MESH","db_id":"D017542"}]},{"id":"21284","type":"Disease","text":["SAH"],"offsets":[[605,608]],"normalized":[{"db_name":"MESH","db_id":"D013345"}]},{"id":"21285","type":"Disease","text":["platelet aggregation"],"offsets":[[795,815]],"normalized":[{"db_name":"MESH","db_id":"D001791"}]},{"id":"21286","type":"Chemical","text":["adenosine diphosphate"],"offsets":[[839,860]],"normalized":[{"db_name":"MESH","db_id":"D000244"}]},{"id":"21287","type":"Chemical","text":["ketoprofen"],"offsets":[[895,905]],"normalized":[{"db_name":"MESH","db_id":"D007660"}]},{"id":"21288","type":"Chemical","text":["ketoprofen"],"offsets":[[946,956]],"normalized":[{"db_name":"MESH","db_id":"D007660"}]},{"id":"21289","type":"Chemical","text":["acetaminophen"],"offsets":[[975,988]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"21290","type":"Disease","text":["platelet aggregation"],"offsets":[[1072,1092]],"normalized":[{"db_name":"MESH","db_id":"D001791"}]},{"id":"21291","type":"Chemical","text":["acetaminophen"],"offsets":[[1110,1123]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"21292","type":"Disease","text":["platelet aggregation"],"offsets":[[1195,1215]],"normalized":[{"db_name":"MESH","db_id":"D001791"}]},{"id":"21293","type":"Chemical","text":["ketoprofen"],"offsets":[[1254,1264]],"normalized":[{"db_name":"MESH","db_id":"D007660"}]},{"id":"21294","type":"Disease","text":["hematoma"],"offsets":[[1310,1318]],"normalized":[{"db_name":"MESH","db_id":"D006406"}]},{"id":"21295","type":"Chemical","text":["Ketoprofen"],"offsets":[[1498,1508]],"normalized":[{"db_name":"MESH","db_id":"D007660"}]},{"id":"21296","type":"Chemical","text":["acetaminophen"],"offsets":[[1517,1530]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"21297","type":"Disease","text":["SAH"],"offsets":[[1575,1578]],"normalized":[{"db_name":"MESH","db_id":"D013345"}]},{"id":"21298","type":"Chemical","text":["ketoprofen"],"offsets":[[1583,1593]],"normalized":[{"db_name":"MESH","db_id":"D007660"}]},{"id":"21299","type":"Disease","text":["artery aneurysms"],"offsets":[[1629,1645]],"normalized":[{"db_name":"MESH","db_id":"D002532"}]},{"id":"21300","type":"Disease","text":["hemorrhage"],"offsets":[[1689,1699]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]}],"events":[],"coreferences":[],"relations":[{"id":"21301","type":"CID","arg1_id":"21279","arg2_id":"21294","normalized":[]},{"id":"21302","type":"CID","arg1_id":"21280","arg2_id":"21294","normalized":[]},{"id":"21303","type":"CID","arg1_id":"21287","arg2_id":"21294","normalized":[]},{"id":"21304","type":"CID","arg1_id":"21288","arg2_id":"21294","normalized":[]},{"id":"21305","type":"CID","arg1_id":"21293","arg2_id":"21294","normalized":[]},{"id":"21306","type":"CID","arg1_id":"21295","arg2_id":"21294","normalized":[]},{"id":"21307","type":"CID","arg1_id":"21298","arg2_id":"21294","normalized":[]},{"id":"21308","type":"CID","arg1_id":"21279","arg2_id":"21285","normalized":[]},{"id":"21309","type":"CID","arg1_id":"21279","arg2_id":"21290","normalized":[]},{"id":"21310","type":"CID","arg1_id":"21279","arg2_id":"21292","normalized":[]},{"id":"21311","type":"CID","arg1_id":"21280","arg2_id":"21285","normalized":[]},{"id":"21312","type":"CID","arg1_id":"21280","arg2_id":"21290","normalized":[]},{"id":"21313","type":"CID","arg1_id":"21280","arg2_id":"21292","normalized":[]},{"id":"21314","type":"CID","arg1_id":"21287","arg2_id":"21285","normalized":[]},{"id":"21315","type":"CID","arg1_id":"21287","arg2_id":"21290","normalized":[]},{"id":"21316","type":"CID","arg1_id":"21287","arg2_id":"21292","normalized":[]},{"id":"21317","type":"CID","arg1_id":"21288","arg2_id":"21285","normalized":[]},{"id":"21318","type":"CID","arg1_id":"21288","arg2_id":"21290","normalized":[]},{"id":"21319","type":"CID","arg1_id":"21288","arg2_id":"21292","normalized":[]},{"id":"21320","type":"CID","arg1_id":"21293","arg2_id":"21285","normalized":[]},{"id":"21321","type":"CID","arg1_id":"21293","arg2_id":"21290","normalized":[]},{"id":"21322","type":"CID","arg1_id":"21293","arg2_id":"21292","normalized":[]},{"id":"21323","type":"CID","arg1_id":"21295","arg2_id":"21285","normalized":[]},{"id":"21324","type":"CID","arg1_id":"21295","arg2_id":"21290","normalized":[]},{"id":"21325","type":"CID","arg1_id":"21295","arg2_id":"21292","normalized":[]},{"id":"21326","type":"CID","arg1_id":"21298","arg2_id":"21285","normalized":[]},{"id":"21327","type":"CID","arg1_id":"21298","arg2_id":"21290","normalized":[]},{"id":"21328","type":"CID","arg1_id":"21298","arg2_id":"21292","normalized":[]}]}
{"id":"21329","document_id":"9523850","passages":[{"id":"21330","type":"title","text":["Value of methylprednisolone in prevention of the arthralgia-myalgia syndrome associated with the total dose infusion of iron dextran: a double blind randomized trial."],"offsets":[[0,166]]},{"id":"21331","type":"abstract","text":["The safety and efficacy of total dose infusion (TDI) of iron dextran has been well documented. In 40% of treated patients, an arthralgia-myalgia syndrome develops. The purpose of this randomized, double-blind, prospective study was to investigate whether intravenous (i.v.) administration of methylprednisolone (MP) prevents this complication. Sixty-five patients, 34 women and 31 men, ages 36 to 80 years, received either normal saline before and after TDI (group 1), 125 mg i.v. MP before and saline after TDI (group 2), or 125 mg i.v. MP before and after TDI (group 3). Patients were observed for 72 hours and reactions were recorded and graded according to severity. Fifty-eight percent of group 1 patients, 33% of group 2, and 26% of group 3 had reactions to TDI. The severity of reactions (minimal, mild, and moderate, respectively) was as follows: group 1--6, 6, and 2; group 2--1, 5, and 0; group 3--5, 1, and 0. Data were analyzed by the two-sided Fisher's exact test using 95% confidence intervals with the approximation of Woolf. These data demonstrate that administration of MP before and after TDI reduces the frequency and severity of the arthralgia-myalgia syndrome. We conclude that 125 mg i.v. MP should be given routinely before and after TDI of iron dextran."],"offsets":[[167,1444]]}],"entities":[{"id":"21332","type":"Chemical","text":["methylprednisolone"],"offsets":[[9,27]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"21333","type":"Disease","text":["arthralgia"],"offsets":[[49,59]],"normalized":[{"db_name":"MESH","db_id":"D018771"}]},{"id":"21334","type":"Disease","text":["myalgia"],"offsets":[[60,67]],"normalized":[{"db_name":"MESH","db_id":"D063806"}]},{"id":"21335","type":"Chemical","text":["iron dextran"],"offsets":[[120,132]],"normalized":[{"db_name":"MESH","db_id":"D007505"}]},{"id":"21336","type":"Chemical","text":["iron dextran"],"offsets":[[223,235]],"normalized":[{"db_name":"MESH","db_id":"D007505"}]},{"id":"21337","type":"Disease","text":["arthralgia"],"offsets":[[293,303]],"normalized":[{"db_name":"MESH","db_id":"D018771"}]},{"id":"21338","type":"Disease","text":["myalgia"],"offsets":[[304,311]],"normalized":[{"db_name":"MESH","db_id":"D063806"}]},{"id":"21339","type":"Chemical","text":["methylprednisolone"],"offsets":[[459,477]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"21340","type":"Chemical","text":["MP"],"offsets":[[479,481]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"21341","type":"Chemical","text":["MP"],"offsets":[[648,650]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"21342","type":"Chemical","text":["MP"],"offsets":[[705,707]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"21343","type":"Chemical","text":["MP"],"offsets":[[1254,1256]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"21344","type":"Disease","text":["arthralgia"],"offsets":[[1320,1330]],"normalized":[{"db_name":"MESH","db_id":"D018771"}]},{"id":"21345","type":"Disease","text":["myalgia"],"offsets":[[1331,1338]],"normalized":[{"db_name":"MESH","db_id":"D063806"}]},{"id":"21346","type":"Chemical","text":["MP"],"offsets":[[1378,1380]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"21347","type":"Chemical","text":["iron dextran"],"offsets":[[1431,1443]],"normalized":[{"db_name":"MESH","db_id":"D007505"}]}],"events":[],"coreferences":[],"relations":[{"id":"21348","type":"CID","arg1_id":"21335","arg2_id":"21333","normalized":[]},{"id":"21349","type":"CID","arg1_id":"21335","arg2_id":"21337","normalized":[]},{"id":"21350","type":"CID","arg1_id":"21335","arg2_id":"21344","normalized":[]},{"id":"21351","type":"CID","arg1_id":"21336","arg2_id":"21333","normalized":[]},{"id":"21352","type":"CID","arg1_id":"21336","arg2_id":"21337","normalized":[]},{"id":"21353","type":"CID","arg1_id":"21336","arg2_id":"21344","normalized":[]},{"id":"21354","type":"CID","arg1_id":"21347","arg2_id":"21333","normalized":[]},{"id":"21355","type":"CID","arg1_id":"21347","arg2_id":"21337","normalized":[]},{"id":"21356","type":"CID","arg1_id":"21347","arg2_id":"21344","normalized":[]}]}
{"id":"21357","document_id":"8384253","passages":[{"id":"21358","type":"title","text":["Long-term effects of vincristine on the peripheral nervous system."],"offsets":[[0,66]]},{"id":"21359","type":"abstract","text":["Forty patients with Non-Hodgkin's Lymphoma treated with vincristine between 1984 and 1990 (cumulative dose 12 mg in 18-24 weeks) were investigated in order to evaluate the long term effects of vincristine on the peripheral nervous system. The patients were interviewed with emphasis on neuropathic symptoms. Physical and quantitative sensory examination with determination of vibratory perception and thermal discrimination thresholds were performed, four to 77 months (median 34 months) after vincristine treatment. Twenty-seven patients reported neuropathic symptoms. In 13 of these 27 patients symptoms were still present at the time of examination. In these patients sensory signs and symptoms predominated. In the other 14 patients symptoms had been present in the past. Symptoms persisted maximally 40 months since cessation of therapy. There was no age difference between patients with and without complaints at the time of examination. Normal reflexes were found in two third of patients. Neuropathic complaints were not very troublesome on the long term. It is concluded that with the above mentioned vincristine dose schedule signs and symptoms of vincristine neuropathy are reversible for a great deal and prognosis is fairly good."],"offsets":[[67,1309]]}],"entities":[{"id":"21360","type":"Chemical","text":["vincristine"],"offsets":[[21,32]],"normalized":[{"db_name":"MESH","db_id":"D014750"}]},{"id":"21361","type":"Disease","text":["Non-Hodgkin's Lymphoma"],"offsets":[[87,109]],"normalized":[{"db_name":"MESH","db_id":"D008228"}]},{"id":"21362","type":"Chemical","text":["vincristine"],"offsets":[[123,134]],"normalized":[{"db_name":"MESH","db_id":"D014750"}]},{"id":"21363","type":"Chemical","text":["vincristine"],"offsets":[[260,271]],"normalized":[{"db_name":"MESH","db_id":"D014750"}]},{"id":"21364","type":"Disease","text":["neuropathic symptoms"],"offsets":[[353,373]],"normalized":[{"db_name":"MESH","db_id":"D012678"}]},{"id":"21365","type":"Chemical","text":["vincristine"],"offsets":[[561,572]],"normalized":[{"db_name":"MESH","db_id":"D014750"}]},{"id":"21366","type":"Disease","text":["neuropathic symptoms"],"offsets":[[615,635]],"normalized":[{"db_name":"MESH","db_id":"D012678"}]},{"id":"21367","type":"Chemical","text":["vincristine"],"offsets":[[1177,1188]],"normalized":[{"db_name":"MESH","db_id":"D014750"}]},{"id":"21368","type":"Chemical","text":["vincristine"],"offsets":[[1225,1236]],"normalized":[{"db_name":"MESH","db_id":"D014750"}]},{"id":"21369","type":"Disease","text":["neuropathy"],"offsets":[[1237,1247]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]}],"events":[],"coreferences":[],"relations":[{"id":"21370","type":"CID","arg1_id":"21360","arg2_id":"21364","normalized":[]},{"id":"21371","type":"CID","arg1_id":"21360","arg2_id":"21366","normalized":[]},{"id":"21372","type":"CID","arg1_id":"21362","arg2_id":"21364","normalized":[]},{"id":"21373","type":"CID","arg1_id":"21362","arg2_id":"21366","normalized":[]},{"id":"21374","type":"CID","arg1_id":"21363","arg2_id":"21364","normalized":[]},{"id":"21375","type":"CID","arg1_id":"21363","arg2_id":"21366","normalized":[]},{"id":"21376","type":"CID","arg1_id":"21365","arg2_id":"21364","normalized":[]},{"id":"21377","type":"CID","arg1_id":"21365","arg2_id":"21366","normalized":[]},{"id":"21378","type":"CID","arg1_id":"21367","arg2_id":"21364","normalized":[]},{"id":"21379","type":"CID","arg1_id":"21367","arg2_id":"21366","normalized":[]},{"id":"21380","type":"CID","arg1_id":"21368","arg2_id":"21364","normalized":[]},{"id":"21381","type":"CID","arg1_id":"21368","arg2_id":"21366","normalized":[]}]}
{"id":"21382","document_id":"8268147","passages":[{"id":"21383","type":"title","text":["A case of polymyositis in a patient with primary biliary cirrhosis treated with D-penicillamine."],"offsets":[[0,96]]},{"id":"21384","type":"abstract","text":["Although D-penicillamine has been used for many rheumatologic diseases, toxicity limits its usefulness in many patients. Polymyositis\/dermatomyositis can develop as one of the autoimmune complications of D-penicillamine treatment, but its exact pathogenesis remains unclear. We report a patient with primary biliary cirrhosis, who developed polymyositis while receiving D-penicillamine therapy. We described the special clinical course of the patient. Patients receiving D-penicillamine therapy should be followed carefully for the development of autoimmune complications like polymyositis\/dermatomyositis."],"offsets":[[97,703]]}],"entities":[{"id":"21385","type":"Disease","text":["polymyositis"],"offsets":[[10,22]],"normalized":[{"db_name":"MESH","db_id":"D017285"}]},{"id":"21386","type":"Disease","text":["primary biliary cirrhosis"],"offsets":[[41,66]],"normalized":[{"db_name":"MESH","db_id":"D008105"}]},{"id":"21387","type":"Chemical","text":["D-penicillamine"],"offsets":[[80,95]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"21388","type":"Chemical","text":["D-penicillamine"],"offsets":[[106,121]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"21389","type":"Disease","text":["rheumatologic diseases"],"offsets":[[145,167]],"normalized":[{"db_name":"MESH","db_id":"D012216"}]},{"id":"21390","type":"Disease","text":["toxicity"],"offsets":[[169,177]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"21391","type":"Disease","text":["Polymyositis"],"offsets":[[218,230]],"normalized":[{"db_name":"MESH","db_id":"D017285"}]},{"id":"21392","type":"Disease","text":["dermatomyositis"],"offsets":[[231,246]],"normalized":[{"db_name":"MESH","db_id":"D003882"}]},{"id":"21393","type":"Chemical","text":["D-penicillamine"],"offsets":[[301,316]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"21394","type":"Disease","text":["primary biliary cirrhosis"],"offsets":[[397,422]],"normalized":[{"db_name":"MESH","db_id":"D008105"}]},{"id":"21395","type":"Disease","text":["polymyositis"],"offsets":[[438,450]],"normalized":[{"db_name":"MESH","db_id":"D017285"}]},{"id":"21396","type":"Chemical","text":["D-penicillamine"],"offsets":[[467,482]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"21397","type":"Chemical","text":["D-penicillamine"],"offsets":[[568,583]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"21398","type":"Disease","text":["polymyositis"],"offsets":[[674,686]],"normalized":[{"db_name":"MESH","db_id":"D017285"}]},{"id":"21399","type":"Disease","text":["dermatomyositis"],"offsets":[[687,702]],"normalized":[{"db_name":"MESH","db_id":"D003882"}]}],"events":[],"coreferences":[],"relations":[{"id":"21400","type":"CID","arg1_id":"21387","arg2_id":"21385","normalized":[]},{"id":"21401","type":"CID","arg1_id":"21387","arg2_id":"21391","normalized":[]},{"id":"21402","type":"CID","arg1_id":"21387","arg2_id":"21395","normalized":[]},{"id":"21403","type":"CID","arg1_id":"21387","arg2_id":"21398","normalized":[]},{"id":"21404","type":"CID","arg1_id":"21388","arg2_id":"21385","normalized":[]},{"id":"21405","type":"CID","arg1_id":"21388","arg2_id":"21391","normalized":[]},{"id":"21406","type":"CID","arg1_id":"21388","arg2_id":"21395","normalized":[]},{"id":"21407","type":"CID","arg1_id":"21388","arg2_id":"21398","normalized":[]},{"id":"21408","type":"CID","arg1_id":"21393","arg2_id":"21385","normalized":[]},{"id":"21409","type":"CID","arg1_id":"21393","arg2_id":"21391","normalized":[]},{"id":"21410","type":"CID","arg1_id":"21393","arg2_id":"21395","normalized":[]},{"id":"21411","type":"CID","arg1_id":"21393","arg2_id":"21398","normalized":[]},{"id":"21412","type":"CID","arg1_id":"21396","arg2_id":"21385","normalized":[]},{"id":"21413","type":"CID","arg1_id":"21396","arg2_id":"21391","normalized":[]},{"id":"21414","type":"CID","arg1_id":"21396","arg2_id":"21395","normalized":[]},{"id":"21415","type":"CID","arg1_id":"21396","arg2_id":"21398","normalized":[]},{"id":"21416","type":"CID","arg1_id":"21397","arg2_id":"21385","normalized":[]},{"id":"21417","type":"CID","arg1_id":"21397","arg2_id":"21391","normalized":[]},{"id":"21418","type":"CID","arg1_id":"21397","arg2_id":"21395","normalized":[]},{"id":"21419","type":"CID","arg1_id":"21397","arg2_id":"21398","normalized":[]}]}
{"id":"21420","document_id":"8251368","passages":[{"id":"21421","type":"title","text":["Photodistributed nifedipine-induced facial telangiectasia."],"offsets":[[0,58]]},{"id":"21422","type":"abstract","text":["Five months after starting nifedipine (Adalat), two patients developed photodistributed facial telangiectasia, which became more noticeable with time. Neither patient complained of photosensitivity or flushing. Both patients reported a significant cosmetic improvement after discontinuing the drug. One commenced the closely related drug amlodipine 3 years later, with recurrence of telangiectasia. The photodistribution of the telangiectasia suggests a significant drug\/light interaction."],"offsets":[[59,548]]}],"entities":[{"id":"21423","type":"Chemical","text":["nifedipine"],"offsets":[[17,27]],"normalized":[{"db_name":"MESH","db_id":"D009543"}]},{"id":"21424","type":"Disease","text":["telangiectasia"],"offsets":[[43,57]],"normalized":[{"db_name":"MESH","db_id":"D013684"}]},{"id":"21425","type":"Chemical","text":["nifedipine"],"offsets":[[86,96]],"normalized":[{"db_name":"MESH","db_id":"D009543"}]},{"id":"21426","type":"Chemical","text":["Adalat"],"offsets":[[98,104]],"normalized":[{"db_name":"MESH","db_id":"D009543"}]},{"id":"21427","type":"Disease","text":["telangiectasia"],"offsets":[[154,168]],"normalized":[{"db_name":"MESH","db_id":"D013684"}]},{"id":"21428","type":"Disease","text":["flushing"],"offsets":[[260,268]],"normalized":[{"db_name":"MESH","db_id":"D005483"}]},{"id":"21429","type":"Chemical","text":["amlodipine"],"offsets":[[397,407]],"normalized":[{"db_name":"MESH","db_id":"D017311"}]},{"id":"21430","type":"Disease","text":["telangiectasia"],"offsets":[[442,456]],"normalized":[{"db_name":"MESH","db_id":"D013684"}]},{"id":"21431","type":"Disease","text":["telangiectasia"],"offsets":[[487,501]],"normalized":[{"db_name":"MESH","db_id":"D013684"}]}],"events":[],"coreferences":[],"relations":[{"id":"21432","type":"CID","arg1_id":"21423","arg2_id":"21424","normalized":[]},{"id":"21433","type":"CID","arg1_id":"21423","arg2_id":"21427","normalized":[]},{"id":"21434","type":"CID","arg1_id":"21423","arg2_id":"21430","normalized":[]},{"id":"21435","type":"CID","arg1_id":"21423","arg2_id":"21431","normalized":[]},{"id":"21436","type":"CID","arg1_id":"21425","arg2_id":"21424","normalized":[]},{"id":"21437","type":"CID","arg1_id":"21425","arg2_id":"21427","normalized":[]},{"id":"21438","type":"CID","arg1_id":"21425","arg2_id":"21430","normalized":[]},{"id":"21439","type":"CID","arg1_id":"21425","arg2_id":"21431","normalized":[]},{"id":"21440","type":"CID","arg1_id":"21426","arg2_id":"21424","normalized":[]},{"id":"21441","type":"CID","arg1_id":"21426","arg2_id":"21427","normalized":[]},{"id":"21442","type":"CID","arg1_id":"21426","arg2_id":"21430","normalized":[]},{"id":"21443","type":"CID","arg1_id":"21426","arg2_id":"21431","normalized":[]},{"id":"21444","type":"CID","arg1_id":"21429","arg2_id":"21424","normalized":[]},{"id":"21445","type":"CID","arg1_id":"21429","arg2_id":"21427","normalized":[]},{"id":"21446","type":"CID","arg1_id":"21429","arg2_id":"21430","normalized":[]},{"id":"21447","type":"CID","arg1_id":"21429","arg2_id":"21431","normalized":[]}]}
{"id":"21448","document_id":"7542793","passages":[{"id":"21449","type":"title","text":["Nephrotoxicity of cyclosporin A and FK506: inhibition of calcineurin phosphatase."],"offsets":[[0,81]]},{"id":"21450","type":"abstract","text":["Cyclosporin A (CsA; 50 mg\/kg) and Fujimycine (FK506; 5 mg\/kg), but not the related macrolide immunosuppressant rapamycin (5 mg\/kg), caused a reduction of glomerular filtration rate, degenerative changes of proximal tubular epithelium, and hypertrophy of the juxtaglomerular apparatus in male Wistar rats when given for 10 days. The molecular mechanisms of CsA and FK506 toxicity were investigated. Cyclophilin A and FK506-binding protein, the main intracytoplasmic receptors for CsA and FK506, respectively, were each detected in renal tissue extract. In the kidney, high levels of immunoreactive and enzymatically active calcineurin were found which were inhibited by the immunosuppressants CsA and FK506, but not by rapamycin. Finally, specific immunophilin-drug-calcineurin complexes formed only in the presence of CsA and FK506, but not rapamycin. These results suggest that the nephrotoxic effects of CsA and FK506 is likely mediated through binding to renal immunophilin and inhibiting calcineurin phosphatase."],"offsets":[[82,1098]]}],"entities":[{"id":"21451","type":"Disease","text":["Nephrotoxicity"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"21452","type":"Chemical","text":["cyclosporin A"],"offsets":[[18,31]],"normalized":[{"db_name":"MESH","db_id":"D016572"}]},{"id":"21453","type":"Chemical","text":["FK506"],"offsets":[[36,41]],"normalized":[{"db_name":"MESH","db_id":"D016559"}]},{"id":"21454","type":"Chemical","text":["Cyclosporin 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{"id":"21510","document_id":"7337133","passages":[{"id":"21511","type":"title","text":["Massive cerebral edema associated with fulminant hepatic failure in acetaminophen overdose: possible role of cranial decompression."],"offsets":[[0,131]]},{"id":"21512","type":"abstract","text":["Cerebral edema may complicate the course of fulminant hepatic failure. Response to conventional therapy has been disappointing. We present a patient with fatal acetaminophen-induced fulminant hepatic failure, with signs and symptoms of cerebral edema, unresponsive to conventional medical therapy. Cranial decompression was carried out. A justification of the need for further evaluation of cranial decompression in such patients is presented."],"offsets":[[132,575]]}],"entities":[{"id":"21513","type":"Disease","text":["cerebral edema"],"offsets":[[8,22]],"normalized":[{"db_name":"MESH","db_id":"D001929"}]},{"id":"21514","type":"Disease","text":["hepatic failure"],"offsets":[[49,64]],"normalized":[{"db_name":"MESH","db_id":"D017093"}]},{"id":"21515","type":"Chemical","text":["acetaminophen"],"offsets":[[68,81]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"21516","type":"Disease","text":["overdose"],"offsets":[[82,90]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"21517","type":"Disease","text":["Cerebral edema"],"offsets":[[132,146]],"normalized":[{"db_name":"MESH","db_id":"D001929"}]},{"id":"21518","type":"Disease","text":["fulminant hepatic failure"],"offsets":[[176,201]],"normalized":[{"db_name":"MESH","db_id":"D017093"}]},{"id":"21519","type":"Chemical","text":["acetaminophen"],"offsets":[[292,305]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"21520","type":"Disease","text":["fulminant hepatic failure"],"offsets":[[314,339]],"normalized":[{"db_name":"MESH","db_id":"D017093"}]},{"id":"21521","type":"Disease","text":["cerebral edema"],"offsets":[[368,382]],"normalized":[{"db_name":"MESH","db_id":"D001929"}]}],"events":[],"coreferences":[],"relations":[{"id":"21522","type":"CID","arg1_id":"21515","arg2_id":"21513","normalized":[]},{"id":"21523","type":"CID","arg1_id":"21515","arg2_id":"21517","normalized":[]},{"id":"21524","type":"CID","arg1_id":"21515","arg2_id":"21521","normalized":[]},{"id":"21525","type":"CID","arg1_id":"21519","arg2_id":"21513","normalized":[]},{"id":"21526","type":"CID","arg1_id":"21519","arg2_id":"21517","normalized":[]},{"id":"21527","type":"CID","arg1_id":"21519","arg2_id":"21521","normalized":[]},{"id":"21528","type":"CID","arg1_id":"21515","arg2_id":"21514","normalized":[]},{"id":"21529","type":"CID","arg1_id":"21515","arg2_id":"21518","normalized":[]},{"id":"21530","type":"CID","arg1_id":"21515","arg2_id":"21520","normalized":[]},{"id":"21531","type":"CID","arg1_id":"21519","arg2_id":"21514","normalized":[]},{"id":"21532","type":"CID","arg1_id":"21519","arg2_id":"21518","normalized":[]},{"id":"21533","type":"CID","arg1_id":"21519","arg2_id":"21520","normalized":[]}]}
{"id":"21534","document_id":"4069770","passages":[{"id":"21535","type":"title","text":["Gentamicin nephropathy in a neonate."],"offsets":[[0,36]]},{"id":"21536","type":"abstract","text":["The clinical and autopsy findings in a premature baby who died of acute renal failure after therapy with gentamicin (5 mg\/kg\/day) and penicillin are presented. The serum gentamicin concentration had reached toxic levels when anuria developed. Numerous periodic acid Schiff (PAS) positive, diastase resistant cytoplasmic inclusion bodies which appeared as myelin figures in cytosegresomes under the electron microscope were identified in the proximal convoluted tubules. The pathological changes induced by gentamicin in the human neonatal kidneys have not been previously reported."],"offsets":[[37,618]]}],"entities":[{"id":"21537","type":"Chemical","text":["Gentamicin"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"21538","type":"Disease","text":["nephropathy"],"offsets":[[11,22]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"21539","type":"Disease","text":["acute renal failure"],"offsets":[[103,122]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"21540","type":"Chemical","text":["gentamicin"],"offsets":[[142,152]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"21541","type":"Chemical","text":["penicillin"],"offsets":[[171,181]],"normalized":[{"db_name":"MESH","db_id":"D010406"}]},{"id":"21542","type":"Chemical","text":["gentamicin"],"offsets":[[207,217]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"21543","type":"Disease","text":["anuria"],"offsets":[[262,268]],"normalized":[{"db_name":"MESH","db_id":"D001002"}]},{"id":"21544","type":"Chemical","text":["periodic acid"],"offsets":[[289,302]],"normalized":[{"db_name":"MESH","db_id":"D010504"}]},{"id":"21545","type":"Chemical","text":["gentamicin"],"offsets":[[543,553]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]}],"events":[],"coreferences":[],"relations":[{"id":"21546","type":"CID","arg1_id":"21537","arg2_id":"21539","normalized":[]},{"id":"21547","type":"CID","arg1_id":"21540","arg2_id":"21539","normalized":[]},{"id":"21548","type":"CID","arg1_id":"21542","arg2_id":"21539","normalized":[]},{"id":"21549","type":"CID","arg1_id":"21545","arg2_id":"21539","normalized":[]}]}
{"id":"21550","document_id":"3780814","passages":[{"id":"21551","type":"title","text":["Anti-carcinogenic action of phenobarbital given simultaneously with diethylnitrosamine in the rat."],"offsets":[[0,98]]},{"id":"21552","type":"abstract","text":["The present work has been planned in order to elucidate the effect of phenobarbital (PB: 15 mg per rat of ingested dose) on carcinogenesis when it is administered simultaneously with diethylnitrosamine (DEN: 10 mg\/kg\/day). Wistar rats (180 g) were treated by DEN alone or by DEN + PB during 2, 4 and 6 weeks according to our schedule for hepatocarcinogenesis. After the end of the treatment, the number and the size of induced PAS positive preneoplastic foci was significantly reduced when PB was given simultaneously with DEN for 4 and 6 weeks. The mitotic inhibition and the production of micronuclei normally observed after partial hepatectomy in DEN treated rats were also significantly decreased in DEN + PB treated rats. When the treatment last only 2 weeks, the presence of PB did not change significantly the last parameters. In DEN + PB treated rats, the survival was prolonged and the tumor incidence decreased as compared with the results obtained by DEN alone. It is concluded that PB, which promotes carcinogenesis when administered after the DEN treatment, reduces the carcinogen effect when given simultaneously with DEN. This 'anti-carcinogen' effect acts on the initiation as well as on the promotion of the precancerous lesions. Biochemical investigations are in progress to obtain more information about this 'paradoxical' PB effect."],"offsets":[[99,1451]]}],"entities":[{"id":"21553","type":"Disease","text":["carcinogenic"],"offsets":[[5,17]],"normalized":[{"db_name":"MESH","db_id":"D063646"}]},{"id":"21554","type":"Chemical","text":["phenobarbital"],"offsets":[[28,41]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"21555","type":"Chemical","text":["diethylnitrosamine"],"offsets":[[68,86]],"normalized":[{"db_name":"MESH","db_id":"D004052"}]},{"id":"21556","type":"Chemical","text":["phenobarbital"],"offsets":[[169,182]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"21557","type":"Chemical","text":["PB"],"offsets":[[184,186]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"21558","type":"Disease","text":["carcinogenesis"],"offsets":[[223,237]],"normalized":[{"db_name":"MESH","db_id":"D063646"}]},{"id":"21559","type":"Chemical","text":["diethylnitrosamine"],"offsets":[[282,300]],"normalized":[{"db_name":"MESH","db_id":"D004052"}]},{"id":"21560","type":"Chemical","text":["DEN"],"offsets":[[302,305]],"normalized":[{"db_name":"MESH","db_id":"D004052"}]},{"id":"21561","type":"Chemical","text":["DEN"],"offsets":[[358,361]],"normalized":[{"db_name":"MESH","db_id":"D004052"}]},{"id":"21562","type":"Chemical","text":["DEN"],"offsets":[[374,377]],"normalized":[{"db_name":"MESH","db_id":"D004052"}]},{"id":"21563","type":"Chemical","text":["PB"],"offsets":[[380,382]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]},{"id":"21564","type":"Disease","text":["hepatocarcinogenesis"],"offsets":[[437,457]],"normalized":[{"db_name":"MESH","db_id":"D063646"}]},{"id":"21565","type":"Disease","text":["preneoplastic 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lesions"],"offsets":[[1324,1344]],"normalized":[{"db_name":"MESH","db_id":"D011230"}]},{"id":"21581","type":"Chemical","text":["PB"],"offsets":[[1441,1443]],"normalized":[{"db_name":"MESH","db_id":"D010634"}]}],"events":[],"coreferences":[],"relations":[{"id":"21582","type":"CID","arg1_id":"21555","arg2_id":"21565","normalized":[]},{"id":"21583","type":"CID","arg1_id":"21555","arg2_id":"21580","normalized":[]},{"id":"21584","type":"CID","arg1_id":"21559","arg2_id":"21565","normalized":[]},{"id":"21585","type":"CID","arg1_id":"21559","arg2_id":"21580","normalized":[]},{"id":"21586","type":"CID","arg1_id":"21560","arg2_id":"21565","normalized":[]},{"id":"21587","type":"CID","arg1_id":"21560","arg2_id":"21580","normalized":[]},{"id":"21588","type":"CID","arg1_id":"21561","arg2_id":"21565","normalized":[]},{"id":"21589","type":"CID","arg1_id":"21561","arg2_id":"21580","normalized":[]},{"id":"21590","type":"CID","arg1_id":"21562","arg2_id":"21565","normalized":[]},{"id":"21591","type":"CID","arg1_id":"21562","arg2_id":"21580","normalized":[]},{"id":"21592","type":"CID","arg1_id":"21567","arg2_id":"21565","normalized":[]},{"id":"21593","type":"CID","arg1_id":"21567","arg2_id":"21580","normalized":[]},{"id":"21594","type":"CID","arg1_id":"21568","arg2_id":"21565","normalized":[]},{"id":"21595","type":"CID","arg1_id":"21568","arg2_id":"21580","normalized":[]},{"id":"21596","type":"CID","arg1_id":"21569","arg2_id":"21565","normalized":[]},{"id":"21597","type":"CID","arg1_id":"21569","arg2_id":"21580","normalized":[]},{"id":"21598","type":"CID","arg1_id":"21572","arg2_id":"21565","normalized":[]},{"id":"21599","type":"CID","arg1_id":"21572","arg2_id":"21580","normalized":[]},{"id":"21600","type":"CID","arg1_id":"21575","arg2_id":"21565","normalized":[]},{"id":"21601","type":"CID","arg1_id":"21575","arg2_id":"21580","normalized":[]},{"id":"21602","type":"CID","arg1_id":"21578","arg2_id":"21565","normalized":[]},{"id":"21603","type":"CID","arg1_id":"21578","arg2_id":"21580","normalized":[]},{"id":"21604","type":"CID","arg1_id":"21579","arg2_id":"21565","normalized":[]},{"id":"21605","type":"CID","arg1_id":"21579","arg2_id":"21580","normalized":[]}]}
{"id":"21606","document_id":"3780697","passages":[{"id":"21607","type":"title","text":["Post-operative rigidity after fentanyl administration."],"offsets":[[0,54]]},{"id":"21608","type":"abstract","text":["A case of thoraco-abdominal rigidity leading to respiratory failure is described in the post-operative period in an elderly patient who received a moderate dose of fentanyl. This was successfully reversed by naloxone. The mechanisms possibly implicated in this accident are discussed."],"offsets":[[55,339]]}],"entities":[{"id":"21609","type":"Disease","text":["rigidity"],"offsets":[[15,23]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"21610","type":"Chemical","text":["fentanyl"],"offsets":[[30,38]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"21611","type":"Disease","text":["rigidity"],"offsets":[[83,91]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"21612","type":"Disease","text":["respiratory failure"],"offsets":[[103,122]],"normalized":[{"db_name":"MESH","db_id":"D012131"}]},{"id":"21613","type":"Chemical","text":["fentanyl"],"offsets":[[219,227]],"normalized":[{"db_name":"MESH","db_id":"D005283"}]},{"id":"21614","type":"Chemical","text":["naloxone"],"offsets":[[263,271]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]}],"events":[],"coreferences":[],"relations":[{"id":"21615","type":"CID","arg1_id":"21610","arg2_id":"21609","normalized":[]},{"id":"21616","type":"CID","arg1_id":"21610","arg2_id":"21611","normalized":[]},{"id":"21617","type":"CID","arg1_id":"21613","arg2_id":"21609","normalized":[]},{"id":"21618","type":"CID","arg1_id":"21613","arg2_id":"21611","normalized":[]}]}
{"id":"21619","document_id":"3686155","passages":[{"id":"21620","type":"title","text":["Postpartum psychosis induced by bromocriptine."],"offsets":[[0,46]]},{"id":"21621","type":"abstract","text":["Two multigravida patients with no prior psychiatric history were seen with postpartum psychosis, having received bromocriptine for inhibition of lactation. Bromocriptine given in high doses has been associated with psychosis in patients receiving the drug for Parkinson's disease. These cases demonstrate that bromocriptine may cause psychosis even when given in low doses."],"offsets":[[47,420]]}],"entities":[{"id":"21622","type":"Disease","text":["psychosis"],"offsets":[[11,20]],"normalized":[{"db_name":"MESH","db_id":"D011605"}]},{"id":"21623","type":"Chemical","text":["bromocriptine"],"offsets":[[32,45]],"normalized":[{"db_name":"MESH","db_id":"D001971"}]},{"id":"21624","type":"Disease","text":["psychiatric"],"offsets":[[87,98]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"21625","type":"Disease","text":["psychosis"],"offsets":[[133,142]],"normalized":[{"db_name":"MESH","db_id":"D011605"}]},{"id":"21626","type":"Chemical","text":["bromocriptine"],"offsets":[[160,173]],"normalized":[{"db_name":"MESH","db_id":"D001971"}]},{"id":"21627","type":"Disease","text":["inhibition of lactation"],"offsets":[[178,201]],"normalized":[{"db_name":"MESH","db_id":"D007775"}]},{"id":"21628","type":"Chemical","text":["Bromocriptine"],"offsets":[[203,216]],"normalized":[{"db_name":"MESH","db_id":"D001971"}]},{"id":"21629","type":"Disease","text":["psychosis"],"offsets":[[262,271]],"normalized":[{"db_name":"MESH","db_id":"D011605"}]},{"id":"21630","type":"Disease","text":["Parkinson's disease"],"offsets":[[307,326]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"21631","type":"Chemical","text":["bromocriptine"],"offsets":[[357,370]],"normalized":[{"db_name":"MESH","db_id":"D001971"}]},{"id":"21632","type":"Disease","text":["psychosis"],"offsets":[[381,390]],"normalized":[{"db_name":"MESH","db_id":"D011605"}]}],"events":[],"coreferences":[],"relations":[{"id":"21633","type":"CID","arg1_id":"21623","arg2_id":"21622","normalized":[]},{"id":"21634","type":"CID","arg1_id":"21623","arg2_id":"21625","normalized":[]},{"id":"21635","type":"CID","arg1_id":"21623","arg2_id":"21629","normalized":[]},{"id":"21636","type":"CID","arg1_id":"21623","arg2_id":"21632","normalized":[]},{"id":"21637","type":"CID","arg1_id":"21626","arg2_id":"21622","normalized":[]},{"id":"21638","type":"CID","arg1_id":"21626","arg2_id":"21625","normalized":[]},{"id":"21639","type":"CID","arg1_id":"21626","arg2_id":"21629","normalized":[]},{"id":"21640","type":"CID","arg1_id":"21626","arg2_id":"21632","normalized":[]},{"id":"21641","type":"CID","arg1_id":"21628","arg2_id":"21622","normalized":[]},{"id":"21642","type":"CID","arg1_id":"21628","arg2_id":"21625","normalized":[]},{"id":"21643","type":"CID","arg1_id":"21628","arg2_id":"21629","normalized":[]},{"id":"21644","type":"CID","arg1_id":"21628","arg2_id":"21632","normalized":[]},{"id":"21645","type":"CID","arg1_id":"21631","arg2_id":"21622","normalized":[]},{"id":"21646","type":"CID","arg1_id":"21631","arg2_id":"21625","normalized":[]},{"id":"21647","type":"CID","arg1_id":"21631","arg2_id":"21629","normalized":[]},{"id":"21648","type":"CID","arg1_id":"21631","arg2_id":"21632","normalized":[]}]}
{"id":"21649","document_id":"3137399","passages":[{"id":"21650","type":"title","text":["A prospective study on the dose dependency of cardiotoxicity induced by mitomycin C."],"offsets":[[0,84]]},{"id":"21651","type":"abstract","text":["Since 1975 mitomycin C (MMC) has been suggested to be cardiotoxic, especially when combined with or given following doxorubicin. Data on dose dependency or incidence concerning this side effect were not known. We have initiated a prospective study to obtain some more data on these subjects. Forty-four MMC-treated patients were studied, 37 of them could be evaluated. All patients were studied by repeated physical examinations, chest X-rays, electro- and echocardiography and radionuclide left ventricular ejection fraction (EF) determinations. The results were evaluated per cumulative dose level. One of the patients developed cardiac failure after 30 mg m-2 MMC and only 150 mg m-2 doxorubicin. The cardiac failure was predicted by a drop in EF determined during a cold pressor test. None of the other patients developed clinical cardiotoxicity, nor did the studied parameters change. The literature on this subject was also reviewed. Based on the combined data from the present study and the literature, we suggest that MMC-related cardiotoxicity is dose dependent, occurring at cumulative dose levels of 30 mg m-2 or more, mainly in patients also (previously or simultaneously) treated with doxorubicin. The incidence is likely to be less than 10% even for this risk group."],"offsets":[[85,1365]]}],"entities":[{"id":"21652","type":"Disease","text":["cardiotoxicity"],"offsets":[[46,60]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"21653","type":"Chemical","text":["mitomycin C"],"offsets":[[72,83]],"normalized":[{"db_name":"MESH","db_id":"D016685"}]},{"id":"21654","type":"Chemical","text":["mitomycin C"],"offsets":[[96,107]],"normalized":[{"db_name":"MESH","db_id":"D016685"}]},{"id":"21655","type":"Chemical","text":["MMC"],"offsets":[[109,112]],"normalized":[{"db_name":"MESH","db_id":"D016685"}]},{"id":"21656","type":"Disease","text":["cardiotoxic"],"offsets":[[139,150]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"21657","type":"Chemical","text":["doxorubicin"],"offsets":[[201,212]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"21658","type":"Chemical","text":["MMC"],"offsets":[[388,391]],"normalized":[{"db_name":"MESH","db_id":"D016685"}]},{"id":"21659","type":"Disease","text":["cardiac failure"],"offsets":[[716,731]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"21660","type":"Chemical","text":["MMC"],"offsets":[[748,751]],"normalized":[{"db_name":"MESH","db_id":"D016685"}]},{"id":"21661","type":"Chemical","text":["doxorubicin"],"offsets":[[772,783]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"21662","type":"Disease","text":["cardiac failure"],"offsets":[[789,804]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"21663","type":"Disease","text":["cardiotoxicity"],"offsets":[[920,934]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"21664","type":"Chemical","text":["MMC"],"offsets":[[1111,1114]],"normalized":[{"db_name":"MESH","db_id":"D016685"}]},{"id":"21665","type":"Disease","text":["cardiotoxicity"],"offsets":[[1123,1137]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"21666","type":"Chemical","text":["doxorubicin"],"offsets":[[1283,1294]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]}],"events":[],"coreferences":[],"relations":[{"id":"21667","type":"CID","arg1_id":"21653","arg2_id":"21659","normalized":[]},{"id":"21668","type":"CID","arg1_id":"21653","arg2_id":"21662","normalized":[]},{"id":"21669","type":"CID","arg1_id":"21654","arg2_id":"21659","normalized":[]},{"id":"21670","type":"CID","arg1_id":"21654","arg2_id":"21662","normalized":[]},{"id":"21671","type":"CID","arg1_id":"21655","arg2_id":"21659","normalized":[]},{"id":"21672","type":"CID","arg1_id":"21655","arg2_id":"21662","normalized":[]},{"id":"21673","type":"CID","arg1_id":"21658","arg2_id":"21659","normalized":[]},{"id":"21674","type":"CID","arg1_id":"21658","arg2_id":"21662","normalized":[]},{"id":"21675","type":"CID","arg1_id":"21660","arg2_id":"21659","normalized":[]},{"id":"21676","type":"CID","arg1_id":"21660","arg2_id":"21662","normalized":[]},{"id":"21677","type":"CID","arg1_id":"21664","arg2_id":"21659","normalized":[]},{"id":"21678","type":"CID","arg1_id":"21664","arg2_id":"21662","normalized":[]},{"id":"21679","type":"CID","arg1_id":"21657","arg2_id":"21659","normalized":[]},{"id":"21680","type":"CID","arg1_id":"21657","arg2_id":"21662","normalized":[]},{"id":"21681","type":"CID","arg1_id":"21661","arg2_id":"21659","normalized":[]},{"id":"21682","type":"CID","arg1_id":"21661","arg2_id":"21662","normalized":[]},{"id":"21683","type":"CID","arg1_id":"21666","arg2_id":"21659","normalized":[]},{"id":"21684","type":"CID","arg1_id":"21666","arg2_id":"21662","normalized":[]}]}
{"id":"21685","document_id":"2709684","passages":[{"id":"21686","type":"title","text":["Phlorizin-induced glycosuria does not prevent gentamicin nephrotoxicity in rats."],"offsets":[[0,80]]},{"id":"21687","type":"abstract","text":["Because rats with streptozotocin-induced diabetes mellitus (DM) have a high solute diuresis (glycosuria of 10 to 12 g\/day), we have suggested that this may in part be responsible for their resistance to gentamicin-induced acute renal failure (ARF). The protection from gentamicin nephrotoxicity was studied in non-diabetic rats with chronic solute diuresis induced by blockage of tubular glucose reabsorption with phlorizin (P). DM rats with mild glycosuria (similar in degree to that of the P treated animals) were also studied. Unanesthetized adult female, Sprague-Dawley rats were divided in four groups and studied for 15 days. Group 1 (P alone) received P, 360 mg\/day, for 15 days; Group II (P + gentamicin); Group III (gentamicin alone) and Group IV (mild DM + gentamicin). Nephrotoxic doses (40 mg\/kg body wt\/day) of gentamicin were injected during the last nine days of study to the animals of groups II to IV. In Group I, P induced a moderate and stable glycosuria (3.9 +\/- 0.1 g\/day, SE), and no functional or morphologic evidence of renal dysfunction (baseline CCr 2.1 +\/- 0.1 ml\/min, undetectable lysozymuria) or damage (tubular necrosis score [maximum 4], zero). In Group II, P did not prevent gentamicin-ARF (maximal decrease in CCr at day 9.89%, P less than 0.001; peak lysozymuria, 1863 +\/- 321 micrograms\/day; and tubular necrosis score, 3.9 +\/- 0.1). These values were not different from those of Group III: maximal decrease in CCr 73% (P less than 0.001); lysozymuria, 2147 +\/- 701 micrograms\/day; tubular necrosis score, 3.8 +\/- 0.1.(ABSTRACT TRUNCATED AT 250 WORDS)"],"offsets":[[81,1667]]}],"entities":[{"id":"21688","type":"Chemical","text":["Phlorizin"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D010695"}]},{"id":"21689","type":"Disease","text":["glycosuria"],"offsets":[[18,28]],"normalized":[{"db_name":"MESH","db_id":"D006029"}]},{"id":"21690","type":"Chemical","text":["gentamicin"],"offsets":[[46,56]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"21691","type":"Disease","text":["nephrotoxicity"],"offsets":[[57,71]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"21692","type":"Chemical","text":["streptozotocin"],"offsets":[[99,113]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"21693","type":"Disease","text":["diabetes mellitus"],"offsets":[[122,139]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"21694","type":"Disease","text":["DM"],"offsets":[[141,143]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"21695","type":"Disease","text":["glycosuria"],"offsets":[[174,184]],"normalized":[{"db_name":"MESH","db_id":"D006029"}]},{"id":"21696","type":"Chemical","text":["gentamicin"],"offsets":[[284,294]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"21697","type":"Disease","text":["acute renal failure"],"offsets":[[303,322]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"21698","type":"Disease","text":["ARF"],"offsets":[[324,327]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"21699","type":"Chemical","text":["gentamicin"],"offsets":[[350,360]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"21700","type":"Disease","text":["nephrotoxicity"],"offsets":[[361,375]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"21701","type":"Disease","text":["diabetic"],"offsets":[[395,403]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"21702","type":"Chemical","text":["glucose"],"offsets":[[469,476]],"normalized":[{"db_name":"MESH","db_id":"D005947"}]},{"id":"21703","type":"Chemical","text":["phlorizin"],"offsets":[[495,504]],"normalized":[{"db_name":"MESH","db_id":"D010695"}]},{"id":"21704","type":"Chemical","text":["P"],"offsets":[[506,507]],"normalized":[{"db_name":"MESH","db_id":"D010695"}]},{"id":"21705","type":"Disease","text":["DM"],"offsets":[[510,512]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"21706","type":"Disease","text":["glycosuria"],"offsets":[[528,538]],"normalized":[{"db_name":"MESH","db_id":"D006029"}]},{"id":"21707","type":"Chemical","text":["P"],"offsets":[[573,574]],"normalized":[{"db_name":"MESH","db_id":"D010695"}]},{"id":"21708","type":"Chemical","text":["P"],"offsets":[[722,723]],"normalized":[{"db_name":"MESH","db_id":"D010695"}]},{"id":"21709","type":"Chemical","text":["P"],"offsets":[[740,741]],"normalized":[{"db_name":"MESH","db_id":"D010695"}]},{"id":"21710","type":"Chemical","text":["P"],"offsets":[[778,779]],"normalized":[{"db_name":"MESH","db_id":"D010695"}]},{"id":"21711","type":"Chemical","text":["gentamicin"],"offsets":[[782,792]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"21712","type":"Chemical","text":["gentamicin"],"offsets":[[806,816]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"21713","type":"Disease","text":["DM"],"offsets":[[843,845]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"21714","type":"Chemical","text":["gentamicin"],"offsets":[[848,858]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"21715","type":"Disease","text":["Nephrotoxic"],"offsets":[[861,872]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"21716","type":"Chemical","text":["gentamicin"],"offsets":[[905,915]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"21717","type":"Chemical","text":["P"],"offsets":[[1012,1013]],"normalized":[{"db_name":"MESH","db_id":"D010695"}]},{"id":"21718","type":"Disease","text":["glycosuria"],"offsets":[[1044,1054]],"normalized":[{"db_name":"MESH","db_id":"D006029"}]},{"id":"21719","type":"Disease","text":["renal dysfunction"],"offsets":[[1125,1142]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"21720","type":"Disease","text":["tubular necrosis"],"offsets":[[1214,1230]],"normalized":[{"db_name":"MESH","db_id":"D009956"}]},{"id":"21721","type":"Chemical","text":["P"],"offsets":[[1270,1271]],"normalized":[{"db_name":"MESH","db_id":"D010695"}]},{"id":"21722","type":"Chemical","text":["gentamicin"],"offsets":[[1288,1298]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"21723","type":"Disease","text":["ARF"],"offsets":[[1299,1302]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"21724","type":"Chemical","text":["P"],"offsets":[[1342,1343]],"normalized":[{"db_name":"MESH","db_id":"D010695"}]},{"id":"21725","type":"Disease","text":["tubular 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necrosis"],"offsets":[[1598,1614]],"normalized":[{"db_name":"MESH","db_id":"D009956"}]}],"events":[],"coreferences":[],"relations":[{"id":"21728","type":"CID","arg1_id":"21692","arg2_id":"21693","normalized":[]},{"id":"21729","type":"CID","arg1_id":"21692","arg2_id":"21694","normalized":[]},{"id":"21730","type":"CID","arg1_id":"21692","arg2_id":"21701","normalized":[]},{"id":"21731","type":"CID","arg1_id":"21692","arg2_id":"21705","normalized":[]},{"id":"21732","type":"CID","arg1_id":"21692","arg2_id":"21713","normalized":[]},{"id":"21733","type":"CID","arg1_id":"21690","arg2_id":"21697","normalized":[]},{"id":"21734","type":"CID","arg1_id":"21690","arg2_id":"21698","normalized":[]},{"id":"21735","type":"CID","arg1_id":"21690","arg2_id":"21723","normalized":[]},{"id":"21736","type":"CID","arg1_id":"21696","arg2_id":"21697","normalized":[]},{"id":"21737","type":"CID","arg1_id":"21696","arg2_id":"21698","normalized":[]},{"id":"21738","type":"CID","arg1_id":"21696","arg2_id":"21723","normalized":[]},{"id":"21739","type":"CID","arg1_id":"21699","arg2_id":"21697","normalized":[]},{"id":"21740","type":"CID","arg1_id":"21699","arg2_id":"21698","normalized":[]},{"id":"21741","type":"CID","arg1_id":"21699","arg2_id":"21723","normalized":[]},{"id":"21742","type":"CID","arg1_id":"21711","arg2_id":"21697","normalized":[]},{"id":"21743","type":"CID","arg1_id":"21711","arg2_id":"21698","normalized":[]},{"id":"21744","type":"CID","arg1_id":"21711","arg2_id":"21723","normalized":[]},{"id":"21745","type":"CID","arg1_id":"21712","arg2_id":"21697","normalized":[]},{"id":"21746","type":"CID","arg1_id":"21712","arg2_id":"21698","normalized":[]},{"id":"21747","type":"CID","arg1_id":"21712","arg2_id":"21723","normalized":[]},{"id":"21748","type":"CID","arg1_id":"21714","arg2_id":"21697","normalized":[]},{"id":"21749","type":"CID","arg1_id":"21714","arg2_id":"21698","normalized":[]},{"id":"21750","type":"CID","arg1_id":"21714","arg2_id":"21723","normalized":[]},{"id":"21751","type":"CID","arg1_id":"21716","arg2_id":"21697","normalized":[]},{"id":"21752","type":"CID","arg1_id":"21716","arg2_id":"21698","normalized":[]},{"id":"21753","type":"CID","arg1_id":"21716","arg2_id":"21723","normalized":[]},{"id":"21754","type":"CID","arg1_id":"21722","arg2_id":"21697","normalized":[]},{"id":"21755","type":"CID","arg1_id":"21722","arg2_id":"21698","normalized":[]},{"id":"21756","type":"CID","arg1_id":"21722","arg2_id":"21723","normalized":[]}]}
{"id":"21757","document_id":"458486","passages":[{"id":"21758","type":"title","text":["Tiapride in levodopa-induced involuntary movements."],"offsets":[[0,51]]},{"id":"21759","type":"abstract","text":["Tiapride, a substituted benzamide derivative closely related to metoclopramide, reduced levodopa-induced peak dose involuntary movements in 16 patients with idiopathic Parkinson's disease. However, an unacceptable increase in disability from Parkinsonism with aggravation of end-of-dose akinesia led to its cessation in 14 patients. Tiapride had no effect on levodopa-induced early morning of \"off-period\" segmental dystonia. These results fail to support the notion that levodopa-induced dyskinesias are caused by overstimulation of a separate group of dopamine receptors."],"offsets":[[52,625]]}],"entities":[{"id":"21760","type":"Chemical","text":["Tiapride"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D063325"}]},{"id":"21761","type":"Chemical","text":["levodopa"],"offsets":[[12,20]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"21762","type":"Disease","text":["involuntary movements"],"offsets":[[29,50]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"21763","type":"Chemical","text":["Tiapride"],"offsets":[[52,60]],"normalized":[{"db_name":"MESH","db_id":"D063325"}]},{"id":"21764","type":"Chemical","text":["benzamide"],"offsets":[[76,85]],"normalized":[{"db_name":"MESH","db_id":"C037689"}]},{"id":"21765","type":"Chemical","text":["metoclopramide"],"offsets":[[116,130]],"normalized":[{"db_name":"MESH","db_id":"D008787"}]},{"id":"21766","type":"Chemical","text":["levodopa"],"offsets":[[140,148]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"21767","type":"Disease","text":["involuntary movements"],"offsets":[[167,188]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"21768","type":"Disease","text":["idiopathic Parkinson's disease"],"offsets":[[209,239]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"21769","type":"Disease","text":["Parkinsonism"],"offsets":[[294,306]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"21770","type":"Disease","text":["akinesia"],"offsets":[[339,347]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"21771","type":"Chemical","text":["Tiapride"],"offsets":[[385,393]],"normalized":[{"db_name":"MESH","db_id":"D063325"}]},{"id":"21772","type":"Chemical","text":["levodopa"],"offsets":[[411,419]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"21773","type":"Disease","text":["dystonia"],"offsets":[[468,476]],"normalized":[{"db_name":"MESH","db_id":"D004421"}]},{"id":"21774","type":"Chemical","text":["levodopa"],"offsets":[[524,532]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"21775","type":"Disease","text":["dyskinesias"],"offsets":[[541,552]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"21776","type":"Chemical","text":["dopamine"],"offsets":[[606,614]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]}],"events":[],"coreferences":[],"relations":[{"id":"21777","type":"CID","arg1_id":"21761","arg2_id":"21762","normalized":[]},{"id":"21778","type":"CID","arg1_id":"21761","arg2_id":"21767","normalized":[]},{"id":"21779","type":"CID","arg1_id":"21761","arg2_id":"21770","normalized":[]},{"id":"21780","type":"CID","arg1_id":"21761","arg2_id":"21775","normalized":[]},{"id":"21781","type":"CID","arg1_id":"21766","arg2_id":"21762","normalized":[]},{"id":"21782","type":"CID","arg1_id":"21766","arg2_id":"21767","normalized":[]},{"id":"21783","type":"CID","arg1_id":"21766","arg2_id":"21770","normalized":[]},{"id":"21784","type":"CID","arg1_id":"21766","arg2_id":"21775","normalized":[]},{"id":"21785","type":"CID","arg1_id":"21772","arg2_id":"21762","normalized":[]},{"id":"21786","type":"CID","arg1_id":"21772","arg2_id":"21767","normalized":[]},{"id":"21787","type":"CID","arg1_id":"21772","arg2_id":"21770","normalized":[]},{"id":"21788","type":"CID","arg1_id":"21772","arg2_id":"21775","normalized":[]},{"id":"21789","type":"CID","arg1_id":"21774","arg2_id":"21762","normalized":[]},{"id":"21790","type":"CID","arg1_id":"21774","arg2_id":"21767","normalized":[]},{"id":"21791","type":"CID","arg1_id":"21774","arg2_id":"21770","normalized":[]},{"id":"21792","type":"CID","arg1_id":"21774","arg2_id":"21775","normalized":[]}]}
{"id":"21793","document_id":"21294084","passages":[{"id":"21794","type":"title","text":["Effects of the hippocampal deep brain stimulation on cortical epileptic discharges in penicillin - induced epilepsy model in rats."],"offsets":[[0,130]]},{"id":"21795","type":"abstract","text":["AIM: Experimental and clinical studies have revealed that hippocampal DBS can control epileptic activity, but the mechanism of action is obscure and optimal stimulation parameters are not clearly defined. The aim was to evaluate the effects of high frequency hippocampal stimulation on cortical epileptic activity in penicillin-induced epilepsy model. MATERIAL AND METHODS: Twenty-five Sprague-Dawley rats were implanted DBS electrodes. In group-1 (n=10) hippocampal DBS was off and in the group-2 (n=10) hippocampal DBS was on (185 Hz, 0.5V, 1V, 2V, and 5V for 60 sec) following penicillin G injection intracortically. In the control group hippocampal DBS was on following 8  l saline injection intracortically. EEG recordings were obtained before and 15 minutes following penicillin-G injection, and at 10th minutes following each stimulus for analysis in terms of frequency, amplitude, and power spectrum. RESULTS: High frequency hippocampal DBS suppressed the acute penicillin-induced cortical epileptic activity independent from stimulus intensity. In the control group, hippocampal stimulation alone lead only to diffuse slowing of cerebral bioelectrical activity at 5V stimulation. CONCLUSION: Our results revealed that continuous high frequency stimulation of the hippocampus suppressed acute cortical epileptic activity effectively without causing secondary epileptic discharges. These results are important in terms of defining the optimal parameters of hippocampal DBS in patients with epilepsy."],"offsets":[[131,1637]]}],"entities":[{"id":"21796","type":"Disease","text":["epileptic"],"offsets":[[62,71]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"21797","type":"Chemical","text":["penicillin"],"offsets":[[86,96]],"normalized":[{"db_name":"MESH","db_id":"D010406"}]},{"id":"21798","type":"Disease","text":["epilepsy"],"offsets":[[107,115]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"21799","type":"Disease","text":["epileptic"],"offsets":[[217,226]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"21800","type":"Disease","text":["epileptic"],"offsets":[[426,435]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"21801","type":"Chemical","text":["penicillin"],"offsets":[[448,458]],"normalized":[{"db_name":"MESH","db_id":"D010406"}]},{"id":"21802","type":"Disease","text":["epilepsy"],"offsets":[[467,475]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"21803","type":"Chemical","text":["penicillin G"],"offsets":[[711,723]],"normalized":[{"db_name":"MESH","db_id":"D010400"}]},{"id":"21804","type":"Chemical","text":["penicillin-G"],"offsets":[[905,917]],"normalized":[{"db_name":"MESH","db_id":"D010400"}]},{"id":"21805","type":"Chemical","text":["penicillin"],"offsets":[[1101,1111]],"normalized":[{"db_name":"MESH","db_id":"D010406"}]},{"id":"21806","type":"Disease","text":["epileptic"],"offsets":[[1129,1138]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"21807","type":"Disease","text":["epileptic"],"offsets":[[1441,1450]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"21808","type":"Disease","text":["epileptic"],"offsets":[[1498,1507]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"21809","type":"Disease","text":["epilepsy"],"offsets":[[1628,1636]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]}],"events":[],"coreferences":[],"relations":[{"id":"21810","type":"CID","arg1_id":"21803","arg2_id":"21796","normalized":[]},{"id":"21811","type":"CID","arg1_id":"21803","arg2_id":"21798","normalized":[]},{"id":"21812","type":"CID","arg1_id":"21803","arg2_id":"21799","normalized":[]},{"id":"21813","type":"CID","arg1_id":"21803","arg2_id":"21800","normalized":[]},{"id":"21814","type":"CID","arg1_id":"21803","arg2_id":"21802","normalized":[]},{"id":"21815","type":"CID","arg1_id":"21803","arg2_id":"21806","normalized":[]},{"id":"21816","type":"CID","arg1_id":"21803","arg2_id":"21807","normalized":[]},{"id":"21817","type":"CID","arg1_id":"21803","arg2_id":"21808","normalized":[]},{"id":"21818","type":"CID","arg1_id":"21803","arg2_id":"21809","normalized":[]},{"id":"21819","type":"CID","arg1_id":"21804","arg2_id":"21796","normalized":[]},{"id":"21820","type":"CID","arg1_id":"21804","arg2_id":"21798","normalized":[]},{"id":"21821","type":"CID","arg1_id":"21804","arg2_id":"21799","normalized":[]},{"id":"21822","type":"CID","arg1_id":"21804","arg2_id":"21800","normalized":[]},{"id":"21823","type":"CID","arg1_id":"21804","arg2_id":"21802","normalized":[]},{"id":"21824","type":"CID","arg1_id":"21804","arg2_id":"21806","normalized":[]},{"id":"21825","type":"CID","arg1_id":"21804","arg2_id":"21807","normalized":[]},{"id":"21826","type":"CID","arg1_id":"21804","arg2_id":"21808","normalized":[]},{"id":"21827","type":"CID","arg1_id":"21804","arg2_id":"21809","normalized":[]}]}
{"id":"21828","document_id":"20727411","passages":[{"id":"21829","type":"title","text":["Neural correlates of S-ketamine induced psychosis during overt continuous verbal fluency."],"offsets":[[0,89]]},{"id":"21830","type":"abstract","text":["The glutamatergic N-methyl-D-aspartate (NMDA) receptor has been implicated in the pathophysiology of schizophrenia. Administered to healthy volunteers, a subanesthetic dose of the non-competitive NMDA receptor antagonist ketamine leads to psychopathological symptoms similar to those observed in schizophrenia. In patients with schizophrenia, ketamine exacerbates the core symptoms of illness, supporting the hypothesis of a glutamatergic dysfunction. In a counterbalanced, placebo-controlled, double-blind study design, healthy subjects were administered a continuous subanesthetic S-ketamine infusion while differences in BOLD responses measured with fMRI were detected. During the scanning period, subjects performed continuous overt verbal fluency tasks (phonological, lexical and semantic). Ketamine-induced psychopathological symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Ketamine elicited psychosis like psychopathology. Post-hoc t-tests revealed significant differences between placebo and ketamine for the amounts of words generated during lexical and semantic verbal fluency, while the phonological domain remained unaffected. Ketamine led to enhanced cortical activations in supramarginal and frontal brain regions for phonological and lexical verbal fluency, but not for semantic verbal fluency. Ketamine induces activation changes in healthy subjects similar to those observed in patients with schizophrenia, particularly in frontal and temporal brain regions. Our results provide further support for the hypothesis of an NMDA receptor dysfunction in the pathophysiology of schizophrenia."],"offsets":[[90,1723]]}],"entities":[{"id":"21831","type":"Chemical","text":["S-ketamine"],"offsets":[[21,31]],"normalized":[]},{"id":"21832","type":"Disease","text":["psychosis"],"offsets":[[40,49]],"normalized":[{"db_name":"MESH","db_id":"D011605"}]},{"id":"21833","type":"Chemical","text":["N-methyl-D-aspartate"],"offsets":[[108,128]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"21834","type":"Chemical","text":["NMDA"],"offsets":[[130,134]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"21835","type":"Disease","text":["schizophrenia"],"offsets":[[191,204]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"21836","type":"Chemical","text":["NMDA"],"offsets":[[286,290]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"21837","type":"Chemical","text":["ketamine"],"offsets":[[311,319]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"21838","type":"Disease","text":["schizophrenia"],"offsets":[[386,399]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"21839","type":"Disease","text":["schizophrenia"],"offsets":[[418,431]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"21840","type":"Chemical","text":["ketamine"],"offsets":[[433,441]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"21841","type":"Disease","text":["glutamatergic dysfunction"],"offsets":[[515,540]],"normalized":[{"db_name":"MESH","db_id":"D018754"}]},{"id":"21842","type":"Chemical","text":["S-ketamine"],"offsets":[[673,683]],"normalized":[]},{"id":"21843","type":"Chemical","text":["Ketamine"],"offsets":[[886,894]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"21844","type":"Chemical","text":["Ketamine"],"offsets":[[1000,1008]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"21845","type":"Disease","text":["psychosis"],"offsets":[[1018,1027]],"normalized":[{"db_name":"MESH","db_id":"D011605"}]},{"id":"21846","type":"Chemical","text":["ketamine"],"offsets":[[1120,1128]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"21847","type":"Chemical","text":["Ketamine"],"offsets":[[1259,1267]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"21848","type":"Chemical","text":["Ketamine"],"offsets":[[1430,1438]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"21849","type":"Disease","text":["schizophrenia"],"offsets":[[1529,1542]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"21850","type":"Chemical","text":["NMDA"],"offsets":[[1657,1661]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"21851","type":"Disease","text":["schizophrenia"],"offsets":[[1709,1722]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]}],"events":[],"coreferences":[],"relations":[{"id":"21852","type":"CID","arg1_id":"21837","arg2_id":"21832","normalized":[]},{"id":"21853","type":"CID","arg1_id":"21837","arg2_id":"21845","normalized":[]},{"id":"21854","type":"CID","arg1_id":"21840","arg2_id":"21832","normalized":[]},{"id":"21855","type":"CID","arg1_id":"21840","arg2_id":"21845","normalized":[]},{"id":"21856","type":"CID","arg1_id":"21843","arg2_id":"21832","normalized":[]},{"id":"21857","type":"CID","arg1_id":"21843","arg2_id":"21845","normalized":[]},{"id":"21858","type":"CID","arg1_id":"21844","arg2_id":"21832","normalized":[]},{"id":"21859","type":"CID","arg1_id":"21844","arg2_id":"21845","normalized":[]},{"id":"21860","type":"CID","arg1_id":"21846","arg2_id":"21832","normalized":[]},{"id":"21861","type":"CID","arg1_id":"21846","arg2_id":"21845","normalized":[]},{"id":"21862","type":"CID","arg1_id":"21847","arg2_id":"21832","normalized":[]},{"id":"21863","type":"CID","arg1_id":"21847","arg2_id":"21845","normalized":[]},{"id":"21864","type":"CID","arg1_id":"21848","arg2_id":"21832","normalized":[]},{"id":"21865","type":"CID","arg1_id":"21848","arg2_id":"21845","normalized":[]}]}
{"id":"21866","document_id":"20533999","passages":[{"id":"21867","type":"title","text":["Dopamine is not essential for the development of methamphetamine-induced neurotoxicity."],"offsets":[[0,87]]},{"id":"21868","type":"abstract","text":["It is widely believed that dopamine (DA) mediates methamphetamine (METH)-induced toxicity to brain dopaminergic neurons, because drugs that interfere with DA neurotransmission decrease toxicity, whereas drugs that increase DA neurotransmission enhance toxicity. However, temperature effects of drugs that have been used to manipulate brain DA neurotransmission confound interpretation of the data. Here we show that the recently reported ability of L-dihydroxyphenylalanine to reverse the protective effect of alpha-methyl-para-tyrosine on METH-induced DA neurotoxicity is also confounded by drug effects on body temperature. Further, we show that mice genetically engineered to be deficient in brain DA develop METH neurotoxicity, as long as the thermic effects of METH are preserved. In addition, we demonstrate that mice genetically engineered to have unilateral brain DA deficits develop METH-induced dopaminergic deficits that are of comparable magnitude on both sides of the brain. Taken together, these findings demonstrate that DA is not essential for the development of METH-induced dopaminergic neurotoxicity and suggest that mechanisms independent of DA warrant more intense investigation."],"offsets":[[88,1288]]}],"entities":[{"id":"21869","type":"Chemical","text":["Dopamine"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"21870","type":"Chemical","text":["methamphetamine"],"offsets":[[49,64]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"21871","type":"Disease","text":["neurotoxicity"],"offsets":[[73,86]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"21872","type":"Chemical","text":["dopamine"],"offsets":[[115,123]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"21873","type":"Chemical","text":["DA"],"offsets":[[125,127]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"21874","type":"Chemical","text":["methamphetamine"],"offsets":[[138,153]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"21875","type":"Chemical","text":["METH"],"offsets":[[155,159]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"21876","type":"Disease","text":["toxicity"],"offsets":[[169,177]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"21877","type":"Chemical","text":["DA"],"offsets":[[243,245]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"21878","type":"Disease","text":["toxicity"],"offsets":[[273,281]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"21879","type":"Chemical","text":["DA"],"offsets":[[311,313]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"21880","type":"Disease","text":["toxicity"],"offsets":[[340,348]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"21881","type":"Chemical","text":["DA"],"offsets":[[428,430]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"21882","type":"Chemical","text":["L-dihydroxyphenylalanine"],"offsets":[[537,561]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"21883","type":"Chemical","text":["alpha-methyl-para-tyrosine"],"offsets":[[598,624]],"normalized":[{"db_name":"MESH","db_id":"D019805"}]},{"id":"21884","type":"Chemical","text":["METH"],"offsets":[[628,632]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"21885","type":"Chemical","text":["DA"],"offsets":[[641,643]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"21886","type":"Disease","text":["neurotoxicity"],"offsets":[[644,657]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"21887","type":"Chemical","text":["DA"],"offsets":[[789,791]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"21888","type":"Chemical","text":["METH"],"offsets":[[800,804]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"21889","type":"Disease","text":["neurotoxicity"],"offsets":[[805,818]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"21890","type":"Chemical","text":["METH"],"offsets":[[854,858]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"21891","type":"Chemical","text":["DA"],"offsets":[[960,962]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"21892","type":"Chemical","text":["METH"],"offsets":[[980,984]],"normalized":[{"db_name":"MESH","db_id":"D008694"}]},{"id":"21893","type":"Disease","text":["dopaminergic 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{"id":"21930","document_id":"20304337","passages":[{"id":"21931","type":"title","text":["Brainstem dysgenesis in an infant prenatally exposed to cocaine."],"offsets":[[0,64]]},{"id":"21932","type":"abstract","text":["Many authors described the effects on the fetus of maternal cocaine abuse during pregnancy. Vasoconstriction appears to be the common mechanism of action leading to a wide range of fetal anomalies. We report on an infant with multiple cranial-nerve involvement attributable to brainstem dysgenesis, born to a cocaine-addicted mother."],"offsets":[[65,398]]}],"entities":[{"id":"21933","type":"Disease","text":["Brainstem dysgenesis"],"offsets":[[0,20]],"normalized":[]},{"id":"21934","type":"Chemical","text":["cocaine"],"offsets":[[56,63]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"21935","type":"Disease","text":["cocaine abuse"],"offsets":[[125,138]],"normalized":[{"db_name":"MESH","db_id":"D019970"}]},{"id":"21936","type":"Disease","text":["fetal anomalies"],"offsets":[[246,261]],"normalized":[{"db_name":"MESH","db_id":"D005315"}]},{"id":"21937","type":"Disease","text":["multiple cranial-nerve involvement"],"offsets":[[291,325]],"normalized":[{"db_name":"MESH","db_id":"D003389"}]},{"id":"21938","type":"Disease","text":["brainstem dysgenesis"],"offsets":[[342,362]],"normalized":[]},{"id":"21939","type":"Disease","text":["cocaine-addicted"],"offsets":[[374,390]],"normalized":[{"db_name":"MESH","db_id":"D019970"}]}],"events":[],"coreferences":[],"relations":[{"id":"21940","type":"CID","arg1_id":"21934","arg2_id":"21937","normalized":[]}]}
{"id":"21941","document_id":"20103708","passages":[{"id":"21942","type":"title","text":["The protective role of Nrf2 in streptozotocin-induced diabetic nephropathy."],"offsets":[[0,75]]},{"id":"21943","type":"abstract","text":["OBJECTIVE: Diabetic nephropathy is one of the major causes of renal failure, which is accompanied by the production of reactive oxygen species (ROS). Nrf2 is the primary transcription factor that controls the antioxidant response essential for maintaining cellular redox homeostasis. Here, we report our findings demonstrating a protective role of Nrf2 against diabetic nephropathy. RESEARCH DESIGN AND METHODS: We explore the protective role of Nrf2 against diabetic nephropathy using human kidney biopsy tissues from diabetic nephropathy patients, a streptozotocin-induced diabetic nephropathy model in Nrf2(-\/-) mice, and cultured human mesangial cells. RESULTS: The glomeruli of human diabetic nephropathy patients were under oxidative stress and had elevated Nrf2 levels. In the animal study, Nrf2 was demonstrated to be crucial in ameliorating streptozotocin-induced renal damage. This is evident by Nrf2(-\/-) mice having higher ROS production and suffering from greater oxidative DNA damage and renal injury compared with Nrf2(+\/+) mice. Mechanistic studies in both in vivo and in vitro systems showed that the Nrf2-mediated protection against diabetic nephropathy is, at least, partially through inhibition of transforming growth factor-beta1 (TGF-beta1) and reduction of extracellular matrix production. In human renal mesangial cells, high glucose induced ROS production and activated expression of Nrf2 and its downstream genes. Furthermore, activation or overexpression of Nrf2 inhibited the promoter activity of TGF-beta1 in a dose-dependent manner, whereas knockdown of Nrf2 by siRNA enhanced TGF-beta1 transcription and fibronectin production. CONCLUSIONS: This work clearly indicates a protective role of Nrf2 in diabetic nephropathy, suggesting that dietary or therapeutic activation of Nrf2 could be used as a strategy to prevent or slow down the progression of diabetic nephropathy."],"offsets":[[76,1977]]}],"entities":[{"id":"21944","type":"Chemical","text":["streptozotocin"],"offsets":[[31,45]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"21945","type":"Disease","text":["diabetic nephropathy"],"offsets":[[54,74]],"normalized":[{"db_name":"MESH","db_id":"D003928"}]},{"id":"21946","type":"Disease","text":["Diabetic nephropathy"],"offsets":[[87,107]],"normalized":[{"db_name":"MESH","db_id":"D003928"}]},{"id":"21947","type":"Disease","text":["renal failure"],"offsets":[[138,151]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"21948","type":"Chemical","text":["oxygen"],"offsets":[[204,210]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"21949","type":"Disease","text":["diabetic nephropathy"],"offsets":[[437,457]],"normalized":[{"db_name":"MESH","db_id":"D003928"}]},{"id":"21950","type":"Disease","text":["diabetic nephropathy"],"offsets":[[535,555]],"normalized":[{"db_name":"MESH","db_id":"D003928"}]},{"id":"21951","type":"Disease","text":["diabetic nephropathy"],"offsets":[[595,615]],"normalized":[{"db_name":"MESH","db_id":"D003928"}]},{"id":"21952","type":"Chemical","text":["streptozotocin"],"offsets":[[628,642]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"21953","type":"Disease","text":["diabetic nephropathy"],"offsets":[[651,671]],"normalized":[{"db_name":"MESH","db_id":"D003928"}]},{"id":"21954","type":"Disease","text":["diabetic nephropathy"],"offsets":[[765,785]],"normalized":[{"db_name":"MESH","db_id":"D003928"}]},{"id":"21955","type":"Chemical","text":["streptozotocin"],"offsets":[[926,940]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"21956","type":"Disease","text":["renal damage"],"offsets":[[949,961]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"21957","type":"Disease","text":["renal injury"],"offsets":[[1078,1090]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"21958","type":"Disease","text":["diabetic nephropathy"],"offsets":[[1227,1247]],"normalized":[{"db_name":"MESH","db_id":"D003928"}]},{"id":"21959","type":"Chemical","text":["glucose"],"offsets":[[1426,1433]],"normalized":[{"db_name":"MESH","db_id":"D005947"}]},{"id":"21960","type":"Disease","text":["diabetic nephropathy"],"offsets":[[1805,1825]],"normalized":[{"db_name":"MESH","db_id":"D003928"}]},{"id":"21961","type":"Disease","text":["diabetic nephropathy"],"offsets":[[1956,1976]],"normalized":[{"db_name":"MESH","db_id":"D003928"}]}],"events":[],"coreferences":[],"relations":[{"id":"21962","type":"CID","arg1_id":"21944","arg2_id":"21945","normalized":[]},{"id":"21963","type":"CID","arg1_id":"21944","arg2_id":"21946","normalized":[]},{"id":"21964","type":"CID","arg1_id":"21944","arg2_id":"21949","normalized":[]},{"id":"21965","type":"CID","arg1_id":"21944","arg2_id":"21950","normalized":[]},{"id":"21966","type":"CID","arg1_id":"21944","arg2_id":"21951","normalized":[]},{"id":"21967","type":"CID","arg1_id":"21944","arg2_id":"21953","normalized":[]},{"id":"21968","type":"CID","arg1_id":"21944","arg2_id":"21954","normalized":[]},{"id":"21969","type":"CID","arg1_id":"21944","arg2_id":"21958","normalized":[]},{"id":"21970","type":"CID","arg1_id":"21944","arg2_id":"21960","normalized":[]},{"id":"21971","type":"CID","arg1_id":"21944","arg2_id":"21961","normalized":[]},{"id":"21972","type":"CID","arg1_id":"21952","arg2_id":"21945","normalized":[]},{"id":"21973","type":"CID","arg1_id":"21952","arg2_id":"21946","normalized":[]},{"id":"21974","type":"CID","arg1_id":"21952","arg2_id":"21949","normalized":[]},{"id":"21975","type":"CID","arg1_id":"21952","arg2_id":"21950","normalized":[]},{"id":"21976","type":"CID","arg1_id":"21952","arg2_id":"21951","normalized":[]},{"id":"21977","type":"CID","arg1_id":"21952","arg2_id":"21953","normalized":[]},{"id":"21978","type":"CID","arg1_id":"21952","arg2_id":"21954","normalized":[]},{"id":"21979","type":"CID","arg1_id":"21952","arg2_id":"21958","normalized":[]},{"id":"21980","type":"CID","arg1_id":"21952","arg2_id":"21960","normalized":[]},{"id":"21981","type":"CID","arg1_id":"21952","arg2_id":"21961","normalized":[]},{"id":"21982","type":"CID","arg1_id":"21955","arg2_id":"21945","normalized":[]},{"id":"21983","type":"CID","arg1_id":"21955","arg2_id":"21946","normalized":[]},{"id":"21984","type":"CID","arg1_id":"21955","arg2_id":"21949","normalized":[]},{"id":"21985","type":"CID","arg1_id":"21955","arg2_id":"21950","normalized":[]},{"id":"21986","type":"CID","arg1_id":"21955","arg2_id":"21951","normalized":[]},{"id":"21987","type":"CID","arg1_id":"21955","arg2_id":"21953","normalized":[]},{"id":"21988","type":"CID","arg1_id":"21955","arg2_id":"21954","normalized":[]},{"id":"21989","type":"CID","arg1_id":"21955","arg2_id":"21958","normalized":[]},{"id":"21990","type":"CID","arg1_id":"21955","arg2_id":"21960","normalized":[]},{"id":"21991","type":"CID","arg1_id":"21955","arg2_id":"21961","normalized":[]}]}
{"id":"21992","document_id":"19996135","passages":[{"id":"21993","type":"title","text":["High-dose tranexamic Acid is associated with nonischemic clinical seizures in cardiac surgical patients."],"offsets":[[0,104]]},{"id":"21994","type":"abstract","text":["BACKGROUND: In 2 separate centers, we observed a notable increase in the incidence of postoperative convulsive seizures from 1.3% to 3.8% in patients having undergone major cardiac surgical procedures. These events were temporally coincident with the initial use of high-dose tranexamic acid (TXA) therapy after withdrawal of aprotinin from general clinical usage. The purpose of this review was to perform a retrospective analysis to examine whether there was a relation between TXA usage and seizures after cardiac surgery. METHODS: An in-depth chart review was undertaken in all 24 patients who developed perioperative seizures. Electroencephalographic activity was recorded in 11 of these patients, and all patients had a formal neurological evaluation and brain imaging studies. RESULTS: Twenty-one of the 24 patients did not have evidence of new cerebral ischemic injury, but seizures were likely due to ischemic brain injury in 3 patients. All patients with seizures did not have permanent neurological abnormalities. All 24 patients with seizures received high doses of TXA intraoperatively ranging from 61 to 259 mg\/kg, had a mean age of 69.9 years, and 21 of 24 had undergone open chamber rather than coronary bypass procedures. All but one patient were managed using cardiopulmonary bypass. No evidence of brain ischemic, metabolic, or hyperthermia-induced causes for their seizures was apparent. CONCLUSION: Our results suggest that use of high-dose TXA in older patients in conjunction with cardiopulmonary bypass and open-chamber cardiac surgery is associated with clinical seizures in susceptible patients."],"offsets":[[105,1726]]}],"entities":[{"id":"21995","type":"Chemical","text":["tranexamic Acid"],"offsets":[[10,25]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]},{"id":"21996","type":"Disease","text":["seizures"],"offsets":[[66,74]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"21997","type":"Disease","text":["convulsive"],"offsets":[[205,215]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"21998","type":"Disease","text":["seizures"],"offsets":[[216,224]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"21999","type":"Chemical","text":["tranexamic acid"],"offsets":[[381,396]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]},{"id":"22000","type":"Chemical","text":["TXA"],"offsets":[[398,401]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]},{"id":"22001","type":"Chemical","text":["TXA"],"offsets":[[585,588]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]},{"id":"22002","type":"Disease","text":["seizures"],"offsets":[[599,607]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22003","type":"Disease","text":["seizures"],"offsets":[[727,735]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22004","type":"Disease","text":["cerebral ischemic injury"],"offsets":[[957,981]],"normalized":[{"db_name":"MESH","db_id":"D001930"}]},{"id":"22005","type":"Disease","text":["seizures"],"offsets":[[987,995]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22006","type":"Disease","text":["ischemic brain injury"],"offsets":[[1015,1036]],"normalized":[{"db_name":"MESH","db_id":"D001930"}]},{"id":"22007","type":"Disease","text":["seizures"],"offsets":[[1070,1078]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22008","type":"Disease","text":["neurological abnormalities"],"offsets":[[1102,1128]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"22009","type":"Disease","text":["seizures"],"offsets":[[1151,1159]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"22010","type":"Chemical","text":["TXA"],"offsets":[[1183,1186]],"normalized":[{"db_name":"MESH","db_id":"D014148"}]},{"id":"22011","type":"Disease","text":["brain 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:"22014","arg2_id":"22003","normalized":[]},{"id":"22071","type":"CID","arg1_id":"22014","arg2_id":"22005","normalized":[]},{"id":"22072","type":"CID","arg1_id":"22014","arg2_id":"22007","normalized":[]},{"id":"22073","type":"CID","arg1_id":"22014","arg2_id":"22009","normalized":[]},{"id":"22074","type":"CID","arg1_id":"22014","arg2_id":"22013","normalized":[]},{"id":"22075","type":"CID","arg1_id":"22014","arg2_id":"22015","normalized":[]}]}
{"id":"22076","document_id":"19674115","passages":[{"id":"22077","type":"title","text":["Recurrent dysosmia induced by pyrazinamide."],"offsets":[[0,43]]},{"id":"22078","type":"abstract","text":["Pyrazinamide can have adverse effects such as hepatic toxicity, hyperuricemia or digestive disorders. In rare cases, alterations in taste and smell function have been reported for pyrazinamide when combined with other drugs. We report a case of reversible olfactory disorder related to pyrazinamide in a woman, with a positive rechallenge. The patient presented every day a sensation of smelling something burning 15 min after drug intake. Dysosmia disappeared completely after pyrazinamide withdrawal and recurred after its rechallenge. The case was reported to the Tunisian Centre of Pharmacovigilance."],"offsets":[[44,648]]}],"entities":[{"id":"22079","type":"Disease","text":["dysosmia"],"offsets":[[10,18]],"normalized":[{"db_name":"MESH","db_id":"D000857"}]},{"id":"22080","type":"Chemical","text":["pyrazinamide"],"offsets":[[30,42]],"normalized":[{"db_name":"MESH","db_id":"D011718"}]},{"id":"22081","type":"Chemical","text":["Pyrazinamide"],"offsets":[[44,56]],"normalized":[{"db_name":"MESH","db_id":"D011718"}]},{"id":"22082","type":"Disease","text":["hepatic toxicity"],"offsets":[[90,106]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"22083","type":"Disease","text":["hyperuricemia"],"offsets":[[108,121]],"normalized":[{"db_name":"MESH","db_id":"D033461"}]},{"id":"22084","type":"Chemical","text":["pyrazinamide"],"offsets":[[224,236]],"normalized":[{"db_name":"MESH","db_id":"D011718"}]},{"id":"22085","type":"Disease","text":["olfactory disorder"],"offsets":[[300,318]],"normalized":[{"db_name":"MESH","db_id":"D000857"}]},{"id":"22086","type":"Chemical","text":["pyrazinamide"],"offsets":[[330,342]],"normalized":[{"db_name":"MESH","db_id":"D011718"}]},{"id":"22087","type":"Disease","text":["Dysosmia"],"offsets":[[484,492]],"normalized":[{"db_name":"MESH","db_id":"D000857"}]},{"id":"22088","type":"Chemical","text":["pyrazinamide"],"offsets":[[522,534]],"normalized":[{"db_name":"MESH","db_id":"D011718"}]}],"events":[],"coreferences":[],"relations":[{"id":"22089","type":"CID","arg1_id":"22080","arg2_id":"22079","normalized":[]},{"id":"22090","type":"CID","arg1_id":"22080","arg2_id":"22085","normalized":[]},{"id":"22091","type":"CID","arg1_id":"22080","arg2_id":"22087","normalized":[]},{"id":"22092","type":"CID","arg1_id":"22081","arg2_id":"22079","normalized":[]},{"id":"22093","type":"CID","arg1_id":"22081","arg2_id":"22085","normalized":[]},{"id":"22094","type":"CID","arg1_id":"22081","arg2_id":"22087","normalized":[]},{"id":"22095","type":"CID","arg1_id":"22084","arg2_id":"22079","normalized":[]},{"id":"22096","type":"CID","arg1_id":"22084","arg2_id":"22085","normalized":[]},{"id":"22097","type":"CID","arg1_id":"22084","arg2_id":"22087","normalized":[]},{"id":"22098","type":"CID","arg1_id":"22086","arg2_id":"22079","normalized":[]},{"id":"22099","type":"CID","arg1_id":"22086","arg2_id":"22085","normalized":[]},{"id":"22100","type":"CID","arg1_id":"22086","arg2_id":"22087","normalized":[]},{"id":"22101","type":"CID","arg1_id":"22088","arg2_id":"22079","normalized":[]},{"id":"22102","type":"CID","arg1_id":"22088","arg2_id":"22085","normalized":[]},{"id":"22103","type":"CID","arg1_id":"22088","arg2_id":"22087","normalized":[]}]}
{"id":"22104","document_id":"19139001","passages":[{"id":"22105","type":"title","text":["Longitudinal assessment of air conduction audiograms in a phase III clinical trial of difluoromethylornithine and sulindac for prevention of sporadic colorectal adenomas."],"offsets":[[0,170]]},{"id":"22106","type":"abstract","text":["A phase III clinical trial assessed the recurrence of adenomatous polyps after treatment for 36 months with difluoromethylornithine (DFMO) plus sulindac or matched placebos. Temporary hearing loss is a known toxicity of treatment with DFMO, thus a comprehensive approach was developed to analyze serial air conduction audiograms. The generalized estimating equation method estimated the mean difference between treatment arms with regard to change in air conduction pure tone thresholds while accounting for within-subject correlation due to repeated measurements at frequencies. Based on 290 subjects, there was an average difference of 0.50 dB between subjects treated with DFMO plus sulindac compared with those treated with placebo (95% confidence interval, -0.64 to 1.63 dB; P = 0.39), adjusted for baseline values, age, and frequencies. In the normal speech range of 500 to 3,000 Hz, an estimated difference of 0.99 dB (-0.17 to 2.14 dB; P = 0.09) was detected. Dose intensity did not add information to models. There were 14 of 151 (9.3%) in the DFMO plus sulindac group and 4 of 139 (2.9%) in the placebo group who experienced at least 15 dB hearing reduction from baseline in 2 or more consecutive frequencies across the entire range tested (P = 0.02). Follow-up air conduction done at least 6 months after end of treatment showed an adjusted mean difference in hearing thresholds of 1.08 dB (-0.81 to 2.96 dB; P = 0.26) between treatment arms. There was no significant difference in the proportion of subjects in the DFMO plus sulindac group who experienced clinically significant hearing loss compared with the placebo group. The estimated attributable risk of ototoxicity from exposure to the drug is 8.4% (95% confidence interval, -2.0% to 18.8%; P = 0.12). There is a <2 dB difference in mean threshold for patients treated with DFMO plus sulindac compared with those treated with placebo."],"offsets":[[171,2074]]}],"entities":[{"id":"22107","type":"Chemical","text":["difluoromethylornithine"],"offsets":[[86,109]],"normalized":[{"db_name":"MESH","db_id":"D000518"}]},{"id":"22108","type":"Chemical","text":["sulindac"],"offsets":[[114,122]],"normalized":[{"db_name":"MESH","db_id":"D013467"}]},{"id":"22109","type":"Disease","text":["colorectal adenomas"],"offsets":[[150,169]],"normalized":[{"db_name":"MESH","db_id":"D015179"}]},{"id":"22110","type":"Disease","text":["adenomatous polyps"],"offsets":[[225,243]],"normalized":[{"db_name":"MESH","db_id":"D018256"}]},{"id":"22111","type":"Chemical","text":["difluoromethylornithine"],"offsets":[[279,302]],"normalized":[{"db_name":"MESH","db_id":"D000518"}]},{"id":"22112","type":"Chemical","text":["DFMO"],"offsets":[[304,308]],"normalized":[{"db_name":"MESH","db_id":"D000518"}]},{"id":"22113","type":"Chemical","text":["sulindac"],"offsets":[[315,323]],"normalized":[{"db_name":"MESH","db_id":"D013467"}]},{"id":"22114","type":"Disease","text":["hearing loss"],"offsets":[[355,367]],"normalized":[{"db_name":"MESH","db_id":"D034381"}]},{"id":"22115","type":"Disease","text":["toxicity"],"offsets":[[379,387]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"22116","type":"Chemical","text":["DFMO"],"offsets":[[406,410]],"normalized":[{"db_name":"MESH","db_id":"D000518"}]},{"id":"22117","type":"Chemical","text":["DFMO"],"offsets":[[847,851]],"normalized":[{"db_name":"MESH","db_id":"D000518"}]},{"id":"22118","type":"Chemical","text":["sulindac"],"offsets":[[857,865]],"normalized":[{"db_name":"MESH","db_id":"D013467"}]},{"id":"22119","type":"Chemical","text":["DFMO"],"offsets":[[1224,1228]],"normalized":[{"db_name":"MESH","db_id":"D000518"}]},{"id":"22120","type":"Chemical","text":["sulindac"],"offsets":[[1234,1242]],"normalized":[{"db_name":"MESH","db_id":"D013467"}]},{"id":"22121","type":"Chemical","text":["DFMO"],"offsets":[[1698,1702]],"normalized":[{"db_name":"MESH","db_id":"D000518"}]},{"id":"22122","type":"Chemical","text":["sulindac"],"offsets":[[1708,1716]],"normalized":[{"db_name":"MESH","db_id":"D013467"}]},{"id":"22123","type":"Disease","text":["hearing loss"],"offsets":[[1762,1774]],"normalized":[{"db_name":"MESH","db_id":"D034381"}]},{"id":"22124","type":"Disease","text":["ototoxicity"],"offsets":[[1843,1854]],"normalized":[{"db_name":"MESH","db_id":"D006311"}]},{"id":"22125","type":"Chemical","text":["DFMO"],"offsets":[[2014,2018]],"normalized":[{"db_name":"MESH","db_id":"D000518"}]},{"id":"22126","type":"Chemical","text":["sulindac"],"offsets":[[2024,2032]],"normalized":[{"db_name":"MESH","db_id":"D013467"}]}],"events":[],"coreferences":[],"relations":[{"id":"22127","type":"CID","arg1_id":"22108","arg2_id":"22114","normalized":[]},{"id":"22128","type":"CID","arg1_id":"22108","arg2_id":"22123","normalized":[]},{"id":"22129","type":"CID","arg1_id":"22113","arg2_id":"22114","normalized":[]},{"id":"22130","type":"CID","arg1_id":"22113","arg2_id":"22123","normalized":[]},{"id":"22131","type":"CID","arg1_id":"22118","arg2_id":"22114","normalized":[]},{"id":"22132","type":"CID","arg1_id":"22118","arg2_id":"22123","normalized":[]},{"id":"22133","type":"CID","arg1_id":"22120","arg2_id":"22114","normalized":[]},{"id":"22134","type":"CID","arg1_id":"22120","arg2_id":"22123","normalized":[]},{"id":"22135","type":"CID","arg1_id":"22122","arg2_id":"22114","normalized":[]},{"id":"22136","type":"CID","arg1_id":"22122","arg2_id":"22123","normalized":[]},{"id":"22137","type":"CID","arg1_id":"22126","arg2_id":"22114","normalized":[]},{"id":"22138","type":"CID","arg1_id":"22126","arg2_id":"22123","normalized":[]}]}
{"id":"22139","document_id":"18239197","passages":[{"id":"22140","type":"title","text":["Increased mental slowing associated with the APOE epsilon4 allele after trihexyphenidyl oral anticholinergic challenge in healthy elderly."],"offsets":[[0,138]]},{"id":"22141","type":"abstract","text":["OBJECTIVES: The objectives of this study were to examine the relationship between APOE epsilon4 and subjective effects of trihexyphenidyl on measures reflecting sedation and confusion and to investigate the relationship between trihexyphenidyl-induced subjective effects and objective memory performance. METHODS: This study comprised 24 cognitively intact, health elderly adults (12 APOE epsilon4 carriers) at an outpatient geriatric psychiatry research clinic. This was a randomized, double blind, placebo-controlled, three-way, crossover experimental design. All participants received 1.0 mg or 2.0 mg trihexyphenidyl or placebo administered in counterbalanced sequences over a period of three consecutive weeks. Bond and Lader's visual analog scales and alternate versions of the Buschke Selective Reminding Test were administered in a repeated measures design at baseline, 1, 2.5, and 5 hours postdrug administration. RESULTS: A 2.0-mg oral dose of trihexyphenidyl resulted in increased subjective ratings of mental slowness in carriers of the APOE epsilon4 allele only. Drug effects as determined by difference scores between 2.0 mg trihexyphenidyl and placebo on ratings of mental slowness significantly correlated with total and delayed recall on the Buschke Selective Reminding Test in carriers of the APOE epsilon4 allele only. However, no significant effects were found with other visual analog scales reflecting subjective sedation and clear-headedness. CONCLUSION: The epsilon4 allele in healthy elderly was associated with increased subjective mental slowing after trihexyphenidyl anticholinergic challenge."],"offsets":[[139,1760]]}],"entities":[{"id":"22142","type":"Disease","text":["mental slowing"],"offsets":[[10,24]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"22143","type":"Chemical","text":["trihexyphenidyl"],"offsets":[[72,87]],"normalized":[{"db_name":"MESH","db_id":"D014282"}]},{"id":"22144","type":"Chemical","text":["trihexyphenidyl"],"offsets":[[261,276]],"normalized":[{"db_name":"MESH","db_id":"D014282"}]},{"id":"22145","type":"Disease","text":["confusion"],"offsets":[[313,322]],"normalized":[{"db_name":"MESH","db_id":"D003221"}]},{"id":"22146","type":"Chemical","text":["trihexyphenidyl"],"offsets":[[367,382]],"normalized":[{"db_name":"MESH","db_id":"D014282"}]},{"id":"22147","type":"Chemical","text":["trihexyphenidyl"],"offsets":[[744,759]],"normalized":[{"db_name":"MESH","db_id":"D014282"}]},{"id":"22148","type":"Chemical","text":["trihexyphenidyl"],"offsets":[[1093,1108]],"normalized":[{"db_name":"MESH","db_id":"D014282"}]},{"id":"22149","type":"Disease","text":["mental slowness"],"offsets":[[1153,1168]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"22150","type":"Chemical","text":["trihexyphenidyl"],"offsets":[[1278,1293]],"normalized":[{"db_name":"MESH","db_id":"D014282"}]},{"id":"22151","type":"Disease","text":["mental slowness"],"offsets":[[1320,1335]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"22152","type":"Disease","text":["mental slowing"],"offsets":[[1697,1711]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"22153","type":"Chemical","text":["trihexyphenidyl"],"offsets":[[1718,1733]],"normalized":[{"db_name":"MESH","db_id":"D014282"}]}],"events":[],"coreferences":[],"relations":[{"id":"22154","type":"CID","arg1_id":"22143","arg2_id":"22142","normalized":[]},{"id":"22155","type":"CID","arg1_id":"22143","arg2_id":"22149","normalized":[]},{"id":"22156","type":"CID","arg1_id":"22143","arg2_id":"22151","normalized":[]},{"id":"22157","type":"CID","arg1_id":"22143","arg2_id":"22152","normalized":[]},{"id":"22158","type":"CID","arg1_id":"22144","arg2_id":"22142","normalized":[]},{"id":"22159","type":"CID","arg1_id":"22144","arg2_id":"22149","normalized":[]},{"id":"22160","type":"CID","arg1_id":"22144","arg2_id":"22151","normalized":[]},{"id":"22161","type":"CID","arg1_id":"22144","arg2_id":"22152","normalized":[]},{"id":"22162","type":"CID","arg1_id":"22146","arg2_id":"22142","normalized":[]},{"id":"22163","type":"CID","arg1_id":"22146","arg2_id":"22149","normalized":[]},{"id":"22164","type":"CID","arg1_id":"22146","arg2_id":"22151","normalized":[]},{"id":"22165","type":"CID","arg1_id":"22146","arg2_id":"22152","normalized":[]},{"id":"22166","type":"CID","arg1_id":"22147","arg2_id":"22142","normalized":[]},{"id":"22167","type":"CID","arg1_id":"22147","arg2_id":"22149","normalized":[]},{"id":"22168","type":"CID","arg1_id":"22147","arg2_id":"22151","normalized":[]},{"id":"22169","type":"CID","arg1_id":"22147","arg2_id":"22152","normalized":[]},{"id":"22170","type":"CID","arg1_id":"22148","arg2_id":"22142","normalized":[]},{"id":"22171","type":"CID","arg1_id":"22148","arg2_id":"22149","normalized":[]},{"id":"22172","type":"CID","arg1_id":"22148","arg2_id":"22151","normalized":[]},{"id":"22173","type":"CID","arg1_id":"22148","arg2_id":"22152","normalized":[]},{"id":"22174","type":"CID","arg1_id":"22150","arg2_id":"22142","normalized":[]},{"id":"22175","type":"CID","arg1_id":"22150","arg2_id":"22149","normalized":[]},{"id":"22176","type":"CID","arg1_id":"22150","arg2_id":"22151","normalized":[]},{"id":"22177","type":"CID","arg1_id":"22150","arg2_id":"22152","normalized":[]},{"id":"22178","type":"CID","arg1_id":"22153","arg2_id":"22142","normalized":[]},{"id":"22179","type":"CID","arg1_id":"22153","arg2_id":"22149","normalized":[]},{"id":"22180","type":"CID","arg1_id":"22153","arg2_id":"22151","normalized":[]},{"id":"22181","type":"CID","arg1_id":"22153","arg2_id":"22152","normalized":[]}]}
{"id":"22182","document_id":"17194457","passages":[{"id":"22183","type":"title","text":["Behavioral effects of pubertal anabolic androgenic steroid exposure in male rats with low serotonin."],"offsets":[[0,100]]},{"id":"22184","type":"abstract","text":["The goal of this study was to assess the interactive effects of chronic anabolic androgenic steroid (AAS) exposure and brain serotonin (5-hydroxytryptamine, 5-HT) depletion on behavior of pubertal male rats. Serotonin was depleted beginning on postnatal day 26 with parachlorophenylalanine (PCPA 100 mg\/kg, every other day); controls received saline. At puberty (P40), half the PCPA-treated rats and half the saline-treated rats began treatment with testosterone (T, 5 mg\/kg, 5 days\/week). Behavioral measures included locomotion, irritability, copulation, partner preference, and aggression. Animals were tested for aggression in their home cage, both with and without physical provocation (mild tail pinch). Brain levels of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were determined using HPLC. PCPA significantly and substantially depleted 5-HT and 5-HIAA in all brain regions examined. Chronic T treatment significantly decreased 5-HT and 5-HIAA in certain brain areas, but to a much lesser extent than PCPA. Chronic exposure to PCPA alone significantly decreased locomotor activity and increased irritability but had no effect on sexual behavior, partner preference, or aggression. T alone had no effect on locomotion, irritability, or sexual behavior but increased partner preference and aggression. The most striking effect of combining T+PCPA was a significant increase in attack frequency as well as a significant decrease in the latency to attack, particularly following physical provocation. Based on these data, it can be speculated that pubertal AAS users with low central 5-HT may be especially prone to exhibit aggressive behavior."],"offsets":[[101,1766]]}],"entities":[{"id":"22185","type":"Chemical","text":["steroid"],"offsets":[[51,58]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"22186","type":"Chemical","text":["serotonin"],"offsets":[[90,99]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"22187","type":"Chemical","text":["steroid"],"offsets":[[193,200]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"22188","type":"Chemical","text":["serotonin"],"offsets":[[226,235]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"22189","type":"Chemical","text":["5-hydroxytryptamine"],"offsets":[[237,256]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"22190","type":"Chemical","text":["5-HT"],"offsets":[[258,262]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"22191","type":"Chemical","text":["Serotonin"],"offsets":[[309,318]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"22192","type":"Chemical","text":["parachlorophenylalanine"],"offsets":[[367,390]],"normalized":[]},{"id":"22193","type":"Chemical","text":["PCPA"],"offsets":[[392,396]],"normalized":[]},{"id":"22194","type":"Chemical","text":["PCPA"],"offsets":[[479,483]],"normalized":[]},{"id":"22195","type":"Chemical","text":["testosterone"],"offsets":[[551,563]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"22196","type":"Chemical","text":["T"],"offsets":[[565,566]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"22197","type":"Disease","text":["irritability"],"offsets":[[632,644]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"22198","type":"Disease","text":["aggression"],"offsets":[[682,692]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"22199","type":"Disease","text":["aggression"],"offsets":[[718,728]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"22200","type":"Chemical","text":["5-HT"],"offsets":[[827,831]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"22201","type":"Chemical","text":["5-hydroxyindoleacetic acid"],"offsets":[[852,878]],"normalized":[{"db_name":"MESH","db_id":"D006897"}]},{"id":"22202","type":"Chemical","text":["5-HIAA"],"offsets":[[880,886]],"normalized":[{"db_name":"MESH","db_id":"D006897"}]},{"id":"22203","type":"Chemical","text":["PCPA"],"offsets":[[917,921]],"normalized":[]},{"id":"22204","type":"Chemical","text":["5-HT"],"offsets":[[963,967]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"22205","type":"Chemical","text":["5-HIAA"],"offsets":[[972,978]],"normalized":[{"db_name":"MESH","db_id":"D006897"}]},{"id":"22206","type":"Chemical","text":["T"],"offsets":[[1018,1019]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"22207","type":"Chemical","text":["5-HT"],"offsets":[[1054,1058]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"22208","type":"Chemical","text":["5-HIAA"],"offsets":[[1063,1069]],"normalized":[{"db_name":"MESH","db_id":"D006897"}]},{"id":"22209","type":"Chemical","text":["PCPA"],"offsets":[[1127,1131]],"normalized":[]},{"id":"22210","type":"Chemical","text":["PCPA"],"offsets":[[1153,1157]],"normalized":[]},{"id":"22211","type":"Disease","text":["irritability"],"offsets":[[1221,1233]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"22212","type":"Disease","text":["aggression"],"offsets":[[1295,1305]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"22213","type":"Chemical","text":["T"],"offsets":[[1307,1308]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"22214","type":"Disease","text":["irritability"],"offsets":[[1344,1356]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"22215","type":"Disease","text":["aggression"],"offsets":[[1414,1424]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"22216","type":"Chemical","text":["T"],"offsets":[[1464,1465]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"22217","type":"Chemical","text":["PCPA"],"offsets":[[1466,1470]],"normalized":[]},{"id":"22218","type":"Chemical","text":["5-HT"],"offsets":[[1706,1710]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"22219","type":"Disease","text":["aggressive behavior"],"offsets":[[1746,1765]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]}],"events":[],"coreferences":[],"relations":[{"id":"22220","type":"CID","arg1_id":"22195","arg2_id":"22197","normalized":[]},{"id":"22221","type":"CID","arg1_id":"22195","arg2_id":"22198","normalized":[]},{"id":"22222","type":"CID","arg1_id":"22195","arg2_id":"22199","normalized":[]},{"id":"22223","type":"CID","arg1_id":"22195","arg2_id":"22211","normalized":[]},{"id":"22224","type":"CID","arg1_id":"22195","arg2_id":"22212","normalized":[]},{"id":"22225","type":"CID","arg1_id":"22195","arg2_id":"22214","normalized":[]},{"id":"22226","type":"CID","arg1_id":"22195","arg2_id":"22215","normalized":[]},{"id":"22227","type":"CID","arg1_id":"22195","arg2_id":"22219","normalized":[]},{"id":"22228","type":"CID","arg1_id":"22196","arg2_id":"22197","normalized":[]},{"id":"22229","type":"CID","arg1_id":"22196","arg2_id":"22198","normalized":[]},{"id":"22230","type":"CID","arg1_id":"22196","arg2_id":"22199","normalized":[]},{"id":"22231","type":"CID","arg1_id":"22196","arg2_id":"22211","normalized":[]},{"id":"22232","type":"CID","arg1_id":"22196","arg2_id":"22212","normalized":[]},{"id":"22233","type":"CID","arg1_id":"22196","arg2_id":"22214","normalized":[]},{"id":"22234","type":"CID","arg1_id":"22196","arg2_id":"22215","normalized":[]},{"id":"22235","type":"CID","arg1_id":"22196","arg2_id":"22219","normalized":[]},{"id":"22236","type":"CID","arg1_id":"22206","arg2_id":"22197","normalized":[]},{"id":"22237","type":"CID","arg1_id":"22206","arg2_id":"22198","normalized":[]},{"id":"22238","type":"CID","arg1_id":"22206","arg2_id":"22199","normalized":[]},{"id":"22239","type":"CID","arg1_id":"22206","arg2_id":"22211","normalized":[]},{"id":"22240","type":"CID","arg1_id":"22206","arg2_id":"22212","normalized":[]},{"id":"22241","type":"CID","arg1_id":"22206","arg2_id":"22214","normalized":[]},{"id":"22242","type":"CID","arg1_id":"22206","arg2_id":"22215","normalized":[]},{"id":"22243","type":"CID","arg1_id":"22206","arg2_id":"22219","normalized":[]},{"id":"22244","type":"CID","arg1_id":"22213","arg2_id":"22197","normalized":[]},{"id":"22245","type":"CID","arg1_id":"22213","arg2_id":"22198","normalized":[]},{"id":"22246","type":"CID","arg1_id":"22213","arg2_id":"22199","normalized":[]},{"id":"22247","type":"CID","arg1_id":"22213","arg2_id":"22211","normalized":[]},{"id":"22248","type":"CID","arg1_id":"22213","arg2_id":"22212","normalized":[]},{"id":"22249","type":"CID","arg1_id":"22213","arg2_id":"22214","normalized":[]},{"id":"22250","type":"CID","arg1_id":"22213","arg2_id":"22215","normalized":[]},{"id":"22251","type":"CID","arg1_id":"22213","arg2_id":"22219","normalized":[]},{"id":"22252","type":"CID","arg1_id":"22216","arg2_id":"22197","normalized":[]},{"id":"22253","type":"CID","arg1_id":"22216","arg2_id":"22198","normalized":[]},{"id":"22254","type":"CID","arg1_id":"22216","arg2_id":"22199","normalized":[]},{"id":"22255","type":"CID","arg1_id":"22216","arg2_id":"22211","normalized":[]},{"id":"22256","type":"CID","arg1_id":"22216","arg2_id":"22212","normalized":[]},{"id":"22257","type":"CID","arg1_id":"22216","arg2_id":"22214","normalized":[]},{"id":"22258","type":"CID","arg1_id":"22216","arg2_id":"22215","normalized":[]},{"id":"22259","type":"CID","arg1_id":"22216","arg2_id":"22219","normalized":[]}]}
{"id":"22260","document_id":"16132524","passages":[{"id":"22261","type":"title","text":["Intracavitary chemotherapy (paclitaxel\/carboplatin liquid crystalline cubic phases) for recurrent glioblastoma -- clinical observations."],"offsets":[[0,136]]},{"id":"22262","type":"abstract","text":["Human malignant brain tumors have a poor prognosis in spite of surgery and radiation therapy. Cubic phases consist of curved biocontinuous lipid bilayers, separating two congruent networks of water channels. Used as a host for cytotoxic drugs, the gel-like matrix can easily be applied to the walls of a surgical resection cavity. For human glioblastoma recurrences, the feasibility, safety, and short-term effects of a surgical intracavitary application of paclitaxel and carboplatin encapsulated by liquid crystalline cubic phases are examined in a pilot study. A total of 12 patients with a recurrence of a glioblastoma multiforme underwent re-resection and received an intracavitary application of paclitaxel and carboplatin cubic phases in different dosages. Six of the patients received more than 15 mg paclitaxel and suffered from moderate to severe brain edema, while the remaining patients received only a total of 15 mg paclitaxel. In the latter group, brain edema was markedly reduced and dealt medically. Intracavitary chemotherapy in recurrent glioblastoma using cubic phases is feasible and safe, yet the clinical benefit remains to be examined in a clinical phase II study."],"offsets":[[137,1325]]}],"entities":[{"id":"22263","type":"Chemical","text":["paclitaxel"],"offsets":[[28,38]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"22264","type":"Chemical","text":["carboplatin"],"offsets":[[39,50]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"22265","type":"Disease","text":["glioblastoma"],"offsets":[[98,110]],"normalized":[{"db_name":"MESH","db_id":"D005909"}]},{"id":"22266","type":"Disease","text":["brain tumors"],"offsets":[[153,165]],"normalized":[{"db_name":"MESH","db_id":"D001932"}]},{"id":"22267","type":"Disease","text":["glioblastoma"],"offsets":[[478,490]],"normalized":[{"db_name":"MESH","db_id":"D005909"}]},{"id":"22268","type":"Chemical","text":["paclitaxel"],"offsets":[[595,605]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"22269","type":"Chemical","text":["carboplatin"],"offsets":[[610,621]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"22270","type":"Disease","text":["glioblastoma"],"offsets":[[747,759]],"normalized":[{"db_name":"MESH","db_id":"D005909"}]},{"id":"22271","type":"Chemical","text":["paclitaxel"],"offsets":[[839,849]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"22272","type":"Chemical","text":["carboplatin"],"offsets":[[854,865]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"22273","type":"Chemical","text":["paclitaxel"],"offsets":[[946,956]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"22274","type":"Disease","text":["brain edema"],"offsets":[[994,1005]],"normalized":[{"db_name":"MESH","db_id":"D001929"}]},{"id":"22275","type":"Chemical","text":["paclitaxel"],"offsets":[[1067,1077]],"normalized":[{"db_name":"MESH","db_id":"D017239"}]},{"id":"22276","type":"Disease","text":["brain edema"],"offsets":[[1100,1111]],"normalized":[{"db_name":"MESH","db_id":"D001929"}]},{"id":"22277","type":"Disease","text":["glioblastoma"],"offsets":[[1194,1206]],"normalized":[{"db_name":"MESH","db_id":"D005909"}]}],"events":[],"coreferences":[],"relations":[{"id":"22278","type":"CID","arg1_id":"22263","arg2_id":"22274","normalized":[]},{"id":"22279","type":"CID","arg1_id":"22263","arg2_id":"22276","normalized":[]},{"id":"22280","type":"CID","arg1_id":"22268","arg2_id":"22274","normalized":[]},{"id":"22281","type":"CID","arg1_id":"22268","arg2_id":"22276","normalized":[]},{"id":"22282","type":"CID","arg1_id":"22271","arg2_id":"22274","normalized":[]},{"id":"22283","type":"CID","arg1_id":"22271","arg2_id":"22276","normalized":[]},{"id":"22284","type":"CID","arg1_id":"22273","arg2_id":"22274","normalized":[]},{"id":"22285","type":"CID","arg1_id":"22273","arg2_id":"22276","normalized":[]},{"id":"22286","type":"CID","arg1_id":"22275","arg2_id":"22274","normalized":[]},{"id":"22287","type":"CID","arg1_id":"22275","arg2_id":"22276","normalized":[]}]}
{"id":"22288","document_id":"12907924","passages":[{"id":"22289","type":"title","text":["Methylphenidate-induced obsessive-compulsive symptoms in an elderly man."],"offsets":[[0,72]]},{"id":"22290","type":"abstract","text":["An 82-year-old man with treatment-resistant depression and early Alzheimer's disease was started on methylphenidate. Significant obsessive-compulsive behavior ensued but diminished over several weeks when methylphenidate was replaced by fluvoxamine. The patient had no prior psychiatric history, but he had a sister with obsessive-compulsive disorder. It appears that methylphenidate precipitated the patient's pathological behavior."],"offsets":[[73,506]]}],"entities":[{"id":"22291","type":"Chemical","text":["Methylphenidate"],"offsets":[[0,15]],"normalized":[{"db_name":"MESH","db_id":"D008774"}]},{"id":"22292","type":"Disease","text":["obsessive-compulsive symptoms"],"offsets":[[24,53]],"normalized":[{"db_name":"MESH","db_id":"D009771"}]},{"id":"22293","type":"Disease","text":["treatment-resistant depression"],"offsets":[[97,127]],"normalized":[{"db_name":"MESH","db_id":"D061218"}]},{"id":"22294","type":"Disease","text":["Alzheimer's disease"],"offsets":[[138,157]],"normalized":[{"db_name":"MESH","db_id":"D000544"}]},{"id":"22295","type":"Chemical","text":["methylphenidate"],"offsets":[[173,188]],"normalized":[{"db_name":"MESH","db_id":"D008774"}]},{"id":"22296","type":"Disease","text":["obsessive-compulsive behavior"],"offsets":[[202,231]],"normalized":[{"db_name":"MESH","db_id":"D009771"}]},{"id":"22297","type":"Chemical","text":["methylphenidate"],"offsets":[[278,293]],"normalized":[{"db_name":"MESH","db_id":"D008774"}]},{"id":"22298","type":"Chemical","text":["fluvoxamine"],"offsets":[[310,321]],"normalized":[{"db_name":"MESH","db_id":"D016666"}]},{"id":"22299","type":"Disease","text":["psychiatric"],"offsets":[[348,359]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"22300","type":"Disease","text":["obsessive-compulsive disorder"],"offsets":[[394,423]],"normalized":[{"db_name":"MESH","db_id":"D009771"}]},{"id":"22301","type":"Chemical","text":["methylphenidate"],"offsets":[[441,456]],"normalized":[{"db_name":"MESH","db_id":"D008774"}]}],"events":[],"coreferences":[],"relations":[{"id":"22302","type":"CID","arg1_id":"22291","arg2_id":"22292","normalized":[]},{"id":"22303","type":"CID","arg1_id":"22291","arg2_id":"22296","normalized":[]},{"id":"22304","type":"CID","arg1_id":"22291","arg2_id":"22300","normalized":[]},{"id":"22305","type":"CID","arg1_id":"22295","arg2_id":"22292","normalized":[]},{"id":"22306","type":"CID","arg1_id":"22295","arg2_id":"22296","normalized":[]},{"id":"22307","type":"CID","arg1_id":"22295","arg2_id":"22300","normalized":[]},{"id":"22308","type":"CID","arg1_id":"22297","arg2_id":"22292","normalized":[]},{"id":"22309","type":"CID","arg1_id":"22297","arg2_id":"22296","normalized":[]},{"id":"22310","type":"CID","arg1_id":"22297","arg2_id":"22300","normalized":[]},{"id":"22311","type":"CID","arg1_id":"22301","arg2_id":"22292","normalized":[]},{"id":"22312","type":"CID","arg1_id":"22301","arg2_id":"22296","normalized":[]},{"id":"22313","type":"CID","arg1_id":"22301","arg2_id":"22300","normalized":[]}]}
{"id":"22314","document_id":"12139551","passages":[{"id":"22315","type":"title","text":["Cardiac arrest after intravenous metoclopramide - a case of five repeated injections of metoclopramide causing five episodes of cardiac arrest."],"offsets":[[0,143]]},{"id":"22316","type":"abstract","text":["We describe a patient where intravenous injection of metoclopramide was immediately followed by asystole repeatedly. The patient received metoclopramide 10 mg i.v. five times during 48 h. After interviewing the attending nurses and reviewing the written documentation, it is clear that every administration of metoclopramide was immediately (within s) followed by asystole. The asystole lasted 15-30 s on four occasions, on one occasion it lasted 2 min. The patient received atropine 0.5-1 mg and chest compressions, before sinus rhythm again took over. We interpret this as episodes of cardiac arrest caused by metoclopramide. The rapid injection via the central venous route and the concomitant tapering of dopamine infusion might have contributed in precipitating the adverse drug reaction."],"offsets":[[144,937]]}],"entities":[{"id":"22317","type":"Disease","text":["Cardiac arrest"],"offsets":[[0,14]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"22318","type":"Chemical","text":["metoclopramide"],"offsets":[[33,47]],"normalized":[{"db_name":"MESH","db_id":"D008787"}]},{"id":"22319","type":"Chemical","text":["metoclopramide"],"offsets":[[88,102]],"normalized":[{"db_name":"MESH","db_id":"D008787"}]},{"id":"22320","type":"Disease","text":["cardiac arrest"],"offsets":[[128,142]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"22321","type":"Chemical","text":["metoclopramide"],"offsets":[[197,211]],"normalized":[{"db_name":"MESH","db_id":"D008787"}]},{"id":"22322","type":"Disease","text":["asystole"],"offsets":[[240,248]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"22323","type":"Chemical","text":["metoclopramide"],"offsets":[[282,296]],"normalized":[{"db_name":"MESH","db_id":"D008787"}]},{"id":"22324","type":"Chemical","text":["metoclopramide"],"offsets":[[454,468]],"normalized":[{"db_name":"MESH","db_id":"D008787"}]},{"id":"22325","type":"Disease","text":["asystole"],"offsets":[[508,516]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"22326","type":"Disease","text":["asystole"],"offsets":[[522,530]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"22327","type":"Chemical","text":["atropine"],"offsets":[[619,627]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"22328","type":"Disease","text":["cardiac arrest"],"offsets":[[731,745]],"normalized":[{"db_name":"MESH","db_id":"D006323"}]},{"id":"22329","type":"Chemical","text":["metoclopramide"],"offsets":[[756,770]],"normalized":[{"db_name":"MESH","db_id":"D008787"}]},{"id":"22330","type":"Chemical","text":["dopamine"],"offsets":[[853,861]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]}],"events":[],"coreferences":[],"relations":[{"id":"22331","type":"CID","arg1_id":"22318","arg2_id":"22317","normalized":[]},{"id":"22332","type":"CID","arg1_id":"22318","arg2_id":"22320","normalized":[]},{"id":"22333","type":"CID","arg1_id":"22318","arg2_id":"22322","normalized":[]},{"id":"22334","type":"CID","arg1_id":"22318","arg2_id":"22325","normalized":[]},{"id":"22335","type":"CID","arg1_id":"22318","arg2_id":"22326","normalized":[]},{"id":"22336","type":"CID","arg1_id":"22318","arg2_id":"22328","normalized":[]},{"id":"22337","type":"CID","arg1_id":"22319","arg2_id":"22317","normalized":[]},{"id":"22338","type":"CID","arg1_id":"22319","arg2_id":"22320","normalized":[]},{"id":"22339","type":"CID","arg1_id":"22319","arg2_id":"22322","normalized":[]},{"id":"22340","type":"CID","arg1_id":"22319","arg2_id":"22325","normalized":[]},{"id":"22341","type":"CID","arg1_id":"22319","arg2_id":"22326","normalized":[]},{"id":"22342","type":"CID","arg1_id":"22319","arg2_id":"22328","normalized":[]},{"id":"22343","type":"CID","arg1_id":"22321","arg2_id":"22317","normalized":[]},{"id":"22344","type":"CID","arg1_id":"22321","arg2_id":"22320","normalized":[]},{"id":"22345","type":"CID","arg1_id":"22321","arg2_id":"22322","normalized":[]},{"id":"22346","type":"CID","arg1_id":"22321","arg2_id":"22325","normalized":[]},{"id":"22347","type":"CID","arg1_id":"22321","arg2_id":"22326","normalized":[]},{"id":"22348","type":"CID","arg1_id":"22321","arg2_id":"22328","normalized":[]},{"id":"22349","type":"CID","arg1_id":"22323","arg2_id":"22317","normalized":[]},{"id":"22350","type":"CID","arg1_id":"22323","arg2_id":"22320","normalized":[]},{"id":"22351","type":"CID","arg1_id":"22323","arg2_id":"22322","normalized":[]},{"id":"22352","type":"CID","arg1_id":"22323","arg2_id":"22325","normalized":[]},{"id":"22353","type":"CID","arg1_id":"22323","arg2_id":"22326","normalized":[]},{"id":"22354","type":"CID","arg1_id":"22323","arg2_id":"22328","normalized":[]},{"id":"22355","type":"CID","arg1_id":"22324","arg2_id":"22317","normalized":[]},{"id":"22356","type":"CID","arg1_id":"22324","arg2_id":"22320","normalized":[]},{"id":"22357","type":"CID","arg1_id":"22324","arg2_id":"22322","normalized":[]},{"id":"22358","type":"CID","arg1_id":"22324","arg2_id":"22325","normalized":[]},{"id":"22359","type":"CID","arg1_id":"22324","arg2_id":"22326","normalized":[]},{"id":"22360","type":"CID","arg1_id":"22324","arg2_id":"22328","normalized":[]},{"id":"22361","type":"CID","arg1_id":"22329","arg2_id":"22317","normalized":[]},{"id":"22362","type":"CID","arg1_id":"22329","arg2_id":"22320","normalized":[]},{"id":"22363","type":"CID","arg1_id":"22329","arg2_id":"22322","normalized":[]},{"id":"22364","type":"CID","arg1_id":"22329","arg2_id":"22325","normalized":[]},{"id":"22365","type":"CID","arg1_id":"22329","arg2_id":"22326","normalized":[]},{"id":"22366","type":"CID","arg1_id":"22329","arg2_id":"22328","normalized":[]}]}
{"id":"22367","document_id":"10411803","passages":[{"id":"22368","type":"title","text":["Severe immune hemolytic anemia associated with prophylactic use of cefotetan in obstetric and gynecologic procedures."],"offsets":[[0,117]]},{"id":"22369","type":"abstract","text":["Second- and third-generation cephalosporins, especially cefotetan, are increasingly associated with severe, sometimes fatal immune hemolytic anemia. We noticed that 10 of our 35 cases of cefotetan-induced hemolytic anemias were in patients who had received cefotetan prophylactically for obstetric and gynecologic procedures. Eight of these cases of severe immune hemolytic anemia are described."],"offsets":[[118,513]]}],"entities":[{"id":"22370","type":"Disease","text":["hemolytic anemia"],"offsets":[[14,30]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"22371","type":"Chemical","text":["cefotetan"],"offsets":[[67,76]],"normalized":[{"db_name":"MESH","db_id":"D015313"}]},{"id":"22372","type":"Chemical","text":["cephalosporins"],"offsets":[[147,161]],"normalized":[{"db_name":"MESH","db_id":"D002511"}]},{"id":"22373","type":"Chemical","text":["cefotetan"],"offsets":[[174,183]],"normalized":[{"db_name":"MESH","db_id":"D015313"}]},{"id":"22374","type":"Disease","text":["hemolytic anemia"],"offsets":[[249,265]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"22375","type":"Chemical","text":["cefotetan"],"offsets":[[305,314]],"normalized":[{"db_name":"MESH","db_id":"D015313"}]},{"id":"22376","type":"Disease","text":["hemolytic anemias"],"offsets":[[323,340]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]},{"id":"22377","type":"Chemical","text":["cefotetan"],"offsets":[[375,384]],"normalized":[{"db_name":"MESH","db_id":"D015313"}]},{"id":"22378","type":"Disease","text":["hemolytic anemia"],"offsets":[[482,498]],"normalized":[{"db_name":"MESH","db_id":"D000743"}]}],"events":[],"coreferences":[],"relations":[{"id":"22379","type":"CID","arg1_id":"22371","arg2_id":"22370","normalized":[]},{"id":"22380","type":"CID","arg1_id":"22371","arg2_id":"22374","normalized":[]},{"id":"22381","type":"CID","arg1_id":"22371","arg2_id":"22376","normalized":[]},{"id":"22382","type":"CID","arg1_id":"22371","arg2_id":"22378","normalized":[]},{"id":"22383","type":"CID","arg1_id":"22373","arg2_id":"22370","normalized":[]},{"id":"22384","type":"CID","arg1_id":"22373","arg2_id":"22374","normalized":[]},{"id":"22385","type":"CID","arg1_id":"22373","arg2_id":"22376","normalized":[]},{"id":"22386","type":"CID","arg1_id":"22373","arg2_id":"22378","normalized":[]},{"id":"22387","type":"CID","arg1_id":"22375","arg2_id":"22370","normalized":[]},{"id":"22388","type":"CID","arg1_id":"22375","arg2_id":"22374","normalized":[]},{"id":"22389","type":"CID","arg1_id":"22375","arg2_id":"22376","normalized":[]},{"id":"22390","type":"CID","arg1_id":"22375","arg2_id":"22378","normalized":[]},{"id":"22391","type":"CID","arg1_id":"22377","arg2_id":"22370","normalized":[]},{"id":"22392","type":"CID","arg1_id":"22377","arg2_id":"22374","normalized":[]},{"id":"22393","type":"CID","arg1_id":"22377","arg2_id":"22376","normalized":[]},{"id":"22394","type":"CID","arg1_id":"22377","arg2_id":"22378","normalized":[]}]}
{"id":"22395","document_id":"10225068","passages":[{"id":"22396","type":"title","text":["Cauda equina syndrome after spinal anaesthesia with hyperbaric 5% lignocaine: a review of six cases of cauda equina syndrome reported to the Swedish Pharmaceutical Insurance 1993-1997."],"offsets":[[0,184]]},{"id":"22397","type":"abstract","text":["Six cases of cauda equina syndrome with varying severity were reported to the Swedish Pharmaceutical Insurance during the period 1993-1997. All were associated with spinal anaesthesia using hyperbaric 5% lignocaine. Five cases had single-shot spinal anaesthesia and one had a repeat spinal anaesthetic due to inadequate block. The dose of hyperbaric 5% lignocaine administered ranged from 60 to 120 mg. Three of the cases were most likely caused by direct neurotoxicity of hyperbaric 5% lignocaine. In the other 3 cases, direct neurotoxicity was also probable, but unfortunately radiological investigations were not done to definitely exclude a compressive aetiology. All cases sustained permanent neurological deficits. We recommend that hyperbaric lignocaine should be administered in concentrations not greater than 2% and at a total dose preferably not exceeding 60 mg."],"offsets":[[185,1058]]}],"entities":[{"id":"22398","type":"Disease","text":["Cauda equina syndrome"],"offsets":[[0,21]],"normalized":[{"db_name":"MESH","db_id":"D011128"}]},{"id":"22399","type":"Chemical","text":["lignocaine"],"offsets":[[66,76]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"22400","type":"Disease","text":["cauda equina syndrome"],"offsets":[[103,124]],"normalized":[{"db_name":"MESH","db_id":"D011128"}]},{"id":"22401","type":"Disease","text":["cauda equina syndrome"],"offsets":[[198,219]],"normalized":[{"db_name":"MESH","db_id":"D011128"}]},{"id":"22402","type":"Chemical","text":["lignocaine"],"offsets":[[389,399]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"22403","type":"Chemical","text":["lignocaine"],"offsets":[[538,548]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"22404","type":"Disease","text":["neurotoxicity"],"offsets":[[641,654]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"22405","type":"Chemical","text":["lignocaine"],"offsets":[[672,682]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]},{"id":"22406","type":"Disease","text":["neurotoxicity"],"offsets":[[713,726]],"normalized":[{"db_name":"MESH","db_id":"D020258"}]},{"id":"22407","type":"Disease","text":["neurological deficits"],"offsets":[[883,904]],"normalized":[{"db_name":"MESH","db_id":"D009461"}]},{"id":"22408","type":"Chemical","text":["lignocaine"],"offsets":[[935,945]],"normalized":[{"db_name":"MESH","db_id":"D008012"}]}],"events":[],"coreferences":[],"relations":[{"id":"22409","type":"CID","arg1_id":"22399","arg2_id":"22398","normalized":[]},{"id":"22410","type":"CID","arg1_id":"22399","arg2_id":"22400","normalized":[]},{"id":"22411","type":"CID","arg1_id":"22399","arg2_id":"22401","normalized":[]},{"id":"22412","type":"CID","arg1_id":"22402","arg2_id":"22398","normalized":[]},{"id":"22413","type":"CID","arg1_id":"22402","arg2_id":"22400","normalized":[]},{"id":"22414","type":"CID","arg1_id":"22402","arg2_id":"22401","normalized":[]},{"id":"22415","type":"CID","arg1_id":"22403","arg2_id":"22398","normalized":[]},{"id":"22416","type":"CID","arg1_id":"22403","arg2_id":"22400","normalized":[]},{"id":"22417","type":"CID","arg1_id":"22403","arg2_id":"22401","normalized":[]},{"id":"22418","type":"CID","arg1_id":"22405","arg2_id":"22398","normalized":[]},{"id":"22419","type":"CID","arg1_id":"22405","arg2_id":"22400","normalized":[]},{"id":"22420","type":"CID","arg1_id":"22405","arg2_id":"22401","normalized":[]},{"id":"22421","type":"CID","arg1_id":"22408","arg2_id":"22398","normalized":[]},{"id":"22422","type":"CID","arg1_id":"22408","arg2_id":"22400","normalized":[]},{"id":"22423","type":"CID","arg1_id":"22408","arg2_id":"22401","normalized":[]}]}
{"id":"22424","document_id":"9549528","passages":[{"id":"22425","type":"title","text":["Cortical motor overactivation in parkinsonian patients with L-dopa-induced peak-dose dyskinesia."],"offsets":[[0,96]]},{"id":"22426","type":"abstract","text":["We have studied the regional cerebral blood flow (rCBF) changes induced by the execution of a finger-to-thumb opposition motor task in the supplementary and primary motor cortex of two groups of parkinsonian patients on L-dopa medication, the first one without L-dopa induced dyskinesia (n = 23) and the other with moderate peak-dose dyskinesia (n = 15), and of a group of 14 normal subjects. Single photon emission tomography with i.v. 133Xe was used to measure the rCBF changes. The dyskinetic parkinsonian patients exhibited a pattern of response which was markedly different from those of the normal subjects and non-dyskinetic parkinsonian patients, with a significant overactivation in the supplementary motor area and the ipsi- and contralateral primary motor areas. These results are compatible with the hypothesis that an hyperkinetic abnormal involuntary movement, like L-dopa-induced peak dose dyskinesia, is due to a disinhibition of the primary and associated motor cortex secondary to an excessive outflow of the pallidothalamocortical motor loop."],"offsets":[[97,1158]]}],"entities":[{"id":"22427","type":"Disease","text":["parkinsonian"],"offsets":[[33,45]],"normalized":[{"db_name":"MESH","db_id":"D020734"}]},{"id":"22428","type":"Chemical","text":["L-dopa"],"offsets":[[60,66]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"22429","type":"Disease","text":["dyskinesia"],"offsets":[[85,95]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"22430","type":"Disease","text":["parkinsonian"],"offsets":[[292,304]],"normalized":[{"db_name":"MESH","db_id":"D020734"}]},{"id":"22431","type":"Chemical","text":["L-dopa"],"offsets":[[317,323]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"22432","type":"Chemical","text":["L-dopa"],"offsets":[[358,364]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"22433","type":"Disease","text":["dyskinesia"],"offsets":[[373,383]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"22434","type":"Disease","text":["dyskinesia"],"offsets":[[431,441]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"22435","type":"Disease","text":["dyskinetic"],"offsets":[[582,592]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"22436","type":"Disease","text":["parkinsonian"],"offsets":[[593,605]],"normalized":[{"db_name":"MESH","db_id":"D020734"}]},{"id":"22437","type":"Disease","text":["dyskinetic"],"offsets":[[718,728]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"22438","type":"Disease","text":["parkinsonian"],"offsets":[[729,741]],"normalized":[{"db_name":"MESH","db_id":"D020734"}]},{"id":"22439","type":"Disease","text":["hyperkinetic"],"offsets":[[928,940]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"22440","type":"Disease","text":["abnormal involuntary movement"],"offsets":[[941,970]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"22441","type":"Chemical","text":["L-dopa"],"offsets":[[977,983]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"22442","type":"Disease","text":["dyskinesia"],"offsets":[[1002,1012]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]}],"events":[],"coreferences":[],"relations":[{"id":"22443","type":"CID","arg1_id":"22428","arg2_id":"22429","normalized":[]},{"id":"22444","type":"CID","arg1_id":"22428","arg2_id":"22433","normalized":[]},{"id":"22445","type":"CID","arg1_id":"22428","arg2_id":"22434","normalized":[]},{"id":"22446","type":"CID","arg1_id":"22428","arg2_id":"22435","normalized":[]},{"id":"22447","type":"CID","arg1_id":"22428","arg2_id":"22437","normalized":[]},{"id":"22448","type":"CID","arg1_id":"22428","arg2_id":"22440","normalized":[]},{"id":"22449","type":"CID","arg1_id":"22428","arg2_id":"22442","normalized":[]},{"id":"22450","type":"CID","arg1_id":"22431","arg2_id":"22429","normalized":[]},{"id":"22451","type":"CID","arg1_id":"22431","arg2_id":"22433","normalized":[]},{"id":"22452","type":"CID","arg1_id":"22431","arg2_id":"22434","normalized":[]},{"id":"22453","type":"CID","arg1_id":"22431","arg2_id":"22435","normalized":[]},{"id":"22454","type":"CID","arg1_id":"22431","arg2_id":"22437","normalized":[]},{"id":"22455","type":"CID","arg1_id":"22431","arg2_id":"22440","normalized":[]},{"id":"22456","type":"CID","arg1_id":"22431","arg2_id":"22442","normalized":[]},{"id":"22457","type":"CID","arg1_id":"22432","arg2_id":"22429","normalized":[]},{"id":"22458","type":"CID","arg1_id":"22432","arg2_id":"22433","normalized":[]},{"id":"22459","type":"CID","arg1_id":"22432","arg2_id":"22434","normalized":[]},{"id":"22460","type":"CID","arg1_id":"22432","arg2_id":"22435","normalized":[]},{"id":"22461","type":"CID","arg1_id":"22432","arg2_id":"22437","normalized":[]},{"id":"22462","type":"CID","arg1_id":"22432","arg2_id":"22440","normalized":[]},{"id":"22463","type":"CID","arg1_id":"22432","arg2_id":"22442","normalized":[]},{"id":"22464","type":"CID","arg1_id":"22441","arg2_id":"22429","normalized":[]},{"id":"22465","type":"CID","arg1_id":"22441","arg2_id":"22433","normalized":[]},{"id":"22466","type":"CID","arg1_id":"22441","arg2_id":"22434","normalized":[]},{"id":"22467","type":"CID","arg1_id":"22441","arg2_id":"22435","normalized":[]},{"id":"22468","type":"CID","arg1_id":"22441","arg2_id":"22437","normalized":[]},{"id":"22469","type":"CID","arg1_id":"22441","arg2_id":"22440","normalized":[]},{"id":"22470","type":"CID","arg1_id":"22441","arg2_id":"22442","normalized":[]}]}
{"id":"22471","document_id":"7843916","passages":[{"id":"22472","type":"title","text":["Dexamethasone-induced ocular hypertension in perfusion-cultured human eyes."],"offsets":[[0,75]]},{"id":"22473","type":"abstract","text":["PURPOSE: Glucocorticoid administration can lead to the development of ocular hypertension and corticosteroid glaucoma in a subset of the population through a decrease in the aqueous humor outflow facility. The purpose of this study was to determine whether glucocorticoid treatment can directly affect the outflow facility of isolated, perfusion-cultured human eyes. METHODS: The anterior segments of human donor eyes from regional eye banks were placed in a constant flow, variable pressure perfusion culture system. Paired eyes were perfused in serum-free media with or without 10(-7) M dexamethasone for 12 days. Intraocular pressure was monitored daily. After incubation, the eyes were morphologically characterized by light microscopy, transmission and scanning electron microscopy, and scanning laser confocal microscopy. RESULTS: A significant increase in intraocular pressure developed in 13 of the 44 pairs of eyes perfused with dexamethasone with an average pressure rise of 17.5 +\/- 3.8 mm Hg after 12 days of dexamethasone exposure. The contralateral control eyes, which did not receive dexamethasone, maintained a stable intraocular pressure during the same period. The outflow pathway of the untreated eyes appeared morphologically normal. In contrast, the dexamethasone-treated hypertensive eyes had thickened trabecular beams, decreased intertrabecular spaces, thickened juxtacanalicular tissue, activated trabecular meshwork cells, and increased amounts of amorphogranular extracellular material, especially in the juxtacanalicular tissue and beneath the endothelial lining of the canal of Schlemm. The dexamethasone-treated nonresponder eyes appeared to be morphologically similar to the untreated eyes, although several subtle dexamethasone-induced morphologic changes were evident. CONCLUSION: Dexamethasone treatment of isolated, perfusion-cultured human eyes led to the generation of ocular hypertension in approximately 30% of the dexamethasone-treated eyes. Steroid treatment resulted in morphologic changes in the trabecular meshwork similar to those reported for corticosteroid glaucoma and open angle glaucoma. This system may provide an acute model in which to study the pathogenic mechanisms involved in steroid glaucoma and primary open angle glaucoma."],"offsets":[[76,2358]]}],"entities":[{"id":"22474","type":"Chemical","text":["Dexamethasone"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"22475","type":"Disease","text":["ocular hypertension"],"offsets":[[22,41]],"normalized":[{"db_name":"MESH","db_id":"D009798"}]},{"id":"22476","type":"Disease","text":["ocular hypertension"],"offsets":[[146,165]],"normalized":[{"db_name":"MESH","db_id":"D009798"}]},{"id":"22477","type":"Disease","text":["corticosteroid glaucoma"],"offsets":[[170,193]],"normalized":[{"db_name":"MESH","db_id":"D005901"}]},{"id":"22478","type":"Chemical","text":["dexamethasone"],"offsets":[[665,678]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"22479","type":"Chemical","text":["dexamethasone"],"offsets":[[1014,1027]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"22480","type":"Chemical","text":["dexamethasone"],"offsets":[[1097,1110]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"22481","type":"Chemical","text":["dexamethasone"],"offsets":[[1175,1188]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"22482","type":"Chemical","text":["dexamethasone"],"offsets":[[1347,1360]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"22483","type":"Disease","text":["hypertensive eyes"],"offsets":[[1369,1386]],"normalized":[{"db_name":"MESH","db_id":"D009798"}]},{"id":"22484","type":"Chemical","text":["dexamethasone"],"offsets":[[1696,1709]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"22485","type":"Chemical","text":["dexamethasone"],"offsets":[[1822,1835]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"22486","type":"Chemical","text":["Dexamethasone"],"offsets":[[1890,1903]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"22487","type":"Disease","text":["ocular hypertension"],"offsets":[[1982,2001]],"normalized":[{"db_name":"MESH","db_id":"D009798"}]},{"id":"22488","type":"Chemical","text":["dexamethasone"],"offsets":[[2030,2043]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"22489","type":"Chemical","text":["Steroid"],"offsets":[[2058,2065]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"22490","type":"Disease","text":["corticosteroid glaucoma"],"offsets":[[2165,2188]],"normalized":[{"db_name":"MESH","db_id":"D005901"}]},{"id":"22491","type":"Disease","text":["open angle glaucoma"],"offsets":[[2193,2212]],"normalized":[{"db_name":"MESH","db_id":"D005902"}]},{"id":"22492","type":"Disease","text":["steroid glaucoma"],"offsets":[[2309,2325]],"normalized":[{"db_name":"MESH","db_id":"D005901"}]},{"id":"22493","type":"Disease","text":["primary open angle glaucoma"],"offsets":[[2330,2357]],"normalized":[{"db_name":"MESH","db_id":"D005902"}]}],"events":[],"coreferences":[],"relations":[{"id":"22494","type":"CID","arg1_id":"22474","arg2_id":"22475","normalized":[]},{"id":"22495","type":"CID","arg1_id":"22474","arg2_id":"22476","normalized":[]},{"id":"22496","type":"CID","arg1_id":"22474","arg2_id":"22483","normalized":[]},{"id":"22497","type":"CID","arg1_id":"22474","arg2_id":"22487","normalized":[]},{"id":"22498","type":"CID","arg1_id":"22478","arg2_id":"22475","normalized":[]},{"id":"22499","type":"CID","arg1_id":"22478","arg2_id":"22476","normalized":[]},{"id":"22500","type":"CID","arg1_id":"22478","arg2_id":"22483","normalized":[]},{"id":"22501","type":"CID","arg1_id":"22478","arg2_id":"22487","normalized":[]},{"id":"22502","type":"CID","arg1_id":"22479","arg2_id":"22475","normalized":[]},{"id":"22503","type":"CID","arg1_id":"22479","arg2_id":"22476","normalized":[]},{"id":"22504","type":"CID","arg1_id":"22479","arg2_id":"22483","normalized":[]},{"id":"22505","type":"CID","arg1_id":"22479","arg2_id":"22487","normalized":[]},{"id":"22506","type":"CID","arg1_id":"22480","arg2_id":"22475","normalized":[]},{"id":"22507","type":"CID","arg1_id":"22480","arg2_id":"22476","normalized":[]},{"id":"22508","type":"CID","arg1_id":"22480","arg2_id":"22483","normalized":[]},{"id":"22509","type":"CID","arg1_id":"22480","arg2_id":"22487","normalized":[]},{"id":"22510","type":"CID","arg1_id":"22481","arg2_id":"22475","normalized":[]},{"id":"22511","type":"CID","arg1_id":"22481","arg2_id":"22476","normalized":[]},{"id":"22512","type":"CID","arg1_id":"22481","arg2_id":"22483","normalized":[]},{"id":"22513","type":"CID","arg1_id":"22481","arg2_id":"22487","normalized":[]},{"id":"22514","type":"CID","arg1_id":"22482","arg2_id":"22475","normalized":[]},{"id":"22515","type":"CID","arg1_id":"22482","arg2_id":"22476","normalized":[]},{"id":"22516","type":"CID","arg1_id":"22482","arg2_id":"22483","normalized":[]},{"id":"22517","type":"CID","arg1_id":"22482","arg2_id":"22487","normalized":[]},{"id":"22518","type":"CID","arg1_id":"22484","arg2_id":"22475","normalized":[]},{"id":"22519","type":"CID","arg1_id":"22484","arg2_id":"22476","normalized":[]},{"id":"22520","type":"CID","arg1_id":"22484","arg2_id":"22483","normalized":[]},{"id":"22521","type":"CID","arg1_id":"22484","arg2_id":"22487","normalized":[]},{"id":"22522","type":"CID","arg1_id":"22485","arg2_id":"22475","normalized":[]},{"id":"22523","type":"CID","arg1_id":"22485","arg2_id":"22476","normalized":[]},{"id":"22524","type":"CID","arg1_id":"22485","arg2_id":"22483","normalized":[]},{"id":"22525","type":"CID","arg1_id":"22485","arg2_id":"22487","normalized":[]},{"id":"22526","type":"CID","arg1_id":"22486","arg2_id":"22475","normalized":[]},{"id":"22527","type":"CID","arg1_id":"22486","arg2_id":"22476","normalized":[]},{"id":"22528","type":"CID","arg1_id":"22486","arg2_id":"22483","normalized":[]},{"id":"22529","type":"CID","arg1_id":"22486","arg2_id":"22487","normalized":[]},{"id":"22530","type":"CID","arg1_id":"22488","arg2_id":"22475","normalized":[]},{"id":"22531","type":"CID","arg1_id":"22488","arg2_id":"22476","normalized":[]},{"id":"22532","type":"CID","arg1_id":"22488","arg2_id":"22483","normalized":[]},{"id":"22533","type":"CID","arg1_id":"22488","arg2_id":"22487","normalized":[]}]}
{"id":"22534","document_id":"7803371","passages":[{"id":"22535","type":"title","text":["Cognitive deterioration from long-term abuse of dextromethorphan: a case report."],"offsets":[[0,80]]},{"id":"22536","type":"abstract","text":["Dextromethorphan (DM), the dextrorotatory isomer of 3-hydroxy-N-methylmorphinan, is the main ingredient in a number of widely available, over-the-counter antitussives. Initial studies (Bornstein 1968) showed that it possessed no respiratory suppressant effects and no addiction liability. Subsequently, however, several articles reporting abuse of this drug have appeared in the literature. The drug is known to cause a variety of acute toxic effects, ranging from nausea, restlessness, insomnia, ataxia, slurred speech and nystagmus to mood changes, perceptual alterations, inattention, disorientation and aggressive behavior (Rammer et al 1988; Katona and Watson 1986; Isbell and Fraser 1953; Devlin et al 1985; McCarthy 1971; Dodds and Revai 1967; Degkwitz 1964; Hildebrand et al 1989). There have also been two reported fatalities from DM overdoses (Fleming 1986). However, there are no reports describing the effects of chronic abuse. This report describes a case of cognitive deterioration resulting from prolonged use of DM."],"offsets":[[81,1112]]}],"entities":[{"id":"22537","type":"Disease","text":["Cognitive deterioration"],"offsets":[[0,23]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"22538","type":"Chemical","text":["dextromethorphan"],"offsets":[[48,64]],"normalized":[{"db_name":"MESH","db_id":"D003915"}]},{"id":"22539","type":"Chemical","text":["Dextromethorphan"],"offsets":[[81,97]],"normalized":[{"db_name":"MESH","db_id":"D003915"}]},{"id":"22540","type":"Chemical","text":["DM"],"offsets":[[99,101]],"normalized":[{"db_name":"MESH","db_id":"D003915"}]},{"id":"22541","type":"Chemical","text":["3-hydroxy-N-methylmorphinan"],"offsets":[[133,160]],"normalized":[{"db_name":"MESH","db_id":"D007981"}]},{"id":"22542","type":"Disease","text":["nausea"],"offsets":[[546,552]],"normalized":[{"db_name":"MESH","db_id":"D009325"}]},{"id":"22543","type":"Disease","text":["restlessness"],"offsets":[[554,566]],"normalized":[{"db_name":"MESH","db_id":"D011595"}]},{"id":"22544","type":"Disease","text":["insomnia"],"offsets":[[568,576]],"normalized":[{"db_name":"MESH","db_id":"D007319"}]},{"id":"22545","type":"Disease","text":["ataxia"],"offsets":[[578,584]],"normalized":[{"db_name":"MESH","db_id":"D001259"}]},{"id":"22546","type":"Disease","text":["nystagmus"],"offsets":[[605,614]],"normalized":[{"db_name":"MESH","db_id":"C564088"}]},{"id":"22547","type":"Disease","text":["aggressive behavior"],"offsets":[[688,707]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"22548","type":"Chemical","text":["DM"],"offsets":[[921,923]],"normalized":[{"db_name":"MESH","db_id":"D003915"}]},{"id":"22549","type":"Disease","text":["cognitive deterioration"],"offsets":[[1053,1076]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"22550","type":"Chemical","text":["DM"],"offsets":[[1109,1111]],"normalized":[{"db_name":"MESH","db_id":"D003915"}]}],"events":[],"coreferences":[],"relations":[{"id":"22551","type":"CID","arg1_id":"22538","arg2_id":"22537","normalized":[]},{"id":"22552","type":"CID","arg1_id":"22538","arg2_id":"22549","normalized":[]},{"id":"22553","type":"CID","arg1_id":"22539","arg2_id":"22537","normalized":[]},{"id":"22554","type":"CID","arg1_id":"22539","arg2_id":"22549","normalized":[]},{"id":"22555","type":"CID","arg1_id":"22540","arg2_id":"22537","normalized":[]},{"id":"22556","type":"CID","arg1_id":"22540","arg2_id":"22549","normalized":[]},{"id":"22557","type":"CID","arg1_id":"22548","arg2_id":"22537","normalized":[]},{"id":"22558","type":"CID","arg1_id":"22548","arg2_id":"22549","normalized":[]},{"id":"22559","type":"CID","arg1_id":"22550","arg2_id":"22537","normalized":[]},{"id":"22560","type":"CID","arg1_id":"22550","arg2_id":"22549","normalized":[]}]}
{"id":"22561","document_id":"7437994","passages":[{"id":"22562","type":"title","text":["Long-term lithium treatment and the kidney. Interim report on fifty patients."],"offsets":[[0,77]]},{"id":"22563","type":"abstract","text":["This is a report on the first part of our study of the effects of long-term lithium treatment on the kidney. Creatinine clearance, maximum urinary osmolality and 24 hour urine volume have been tested in 50 affectively ill patients who have been on long-term lithium for more than one year. These findings have been compared with norms and with values of the same tests from screening prior to lithium, available for most of our patients. No evidence was found for any reduction of glomerular filtration during lithium treatment. Low clearance values found in several patients could be accounted for by their age and their pre-lithium values. Urinary concentration defect appeared frequent but the extent of the impairment is difficult to assess because of the uncertainty about the norms applicable to this group of patients. The concentration defect appeared reversible, at least in part. Polyuria above 3 litres\/24 hours was found in 10% of patients. An attempt is made to draw practical conclusions from the preliminary findings."],"offsets":[[78,1110]]}],"entities":[{"id":"22564","type":"Chemical","text":["lithium"],"offsets":[[10,17]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"22565","type":"Chemical","text":["lithium"],"offsets":[[154,161]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"22566","type":"Chemical","text":["Creatinine"],"offsets":[[187,197]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"22567","type":"Chemical","text":["lithium"],"offsets":[[336,343]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"22568","type":"Chemical","text":["lithium"],"offsets":[[471,478]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"22569","type":"Chemical","text":["lithium"],"offsets":[[588,595]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"22570","type":"Chemical","text":["lithium"],"offsets":[[704,711]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"22571","type":"Disease","text":["Polyuria"],"offsets":[[968,976]],"normalized":[{"db_name":"MESH","db_id":"D011141"}]}],"events":[],"coreferences":[],"relations":[{"id":"22572","type":"CID","arg1_id":"22564","arg2_id":"22571","normalized":[]},{"id":"22573","type":"CID","arg1_id":"22565","arg2_id":"22571","normalized":[]},{"id":"22574","type":"CID","arg1_id":"22567","arg2_id":"22571","normalized":[]},{"id":"22575","type":"CID","arg1_id":"22568","arg2_id":"22571","normalized":[]},{"id":"22576","type":"CID","arg1_id":"22569","arg2_id":"22571","normalized":[]},{"id":"22577","type":"CID","arg1_id":"22570","arg2_id":"22571","normalized":[]}]}
{"id":"22578","document_id":"6496797","passages":[{"id":"22579","type":"title","text":["Complete heart block following a single dose of trazodone."],"offsets":[[0,58]]},{"id":"22580","type":"abstract","text":["Forty minutes after receiving a single starting dose of trazodone, a patient developed complete heart block. The case illustrates that, despite the results of earlier studies, trazodone's effect on cardiac conduction may be severe in individuals at risk for conduction delay."],"offsets":[[59,334]]}],"entities":[{"id":"22581","type":"Disease","text":["heart block"],"offsets":[[9,20]],"normalized":[{"db_name":"MESH","db_id":"D006327"}]},{"id":"22582","type":"Chemical","text":["trazodone"],"offsets":[[48,57]],"normalized":[{"db_name":"MESH","db_id":"D014196"}]},{"id":"22583","type":"Chemical","text":["trazodone"],"offsets":[[115,124]],"normalized":[{"db_name":"MESH","db_id":"D014196"}]},{"id":"22584","type":"Disease","text":["heart block"],"offsets":[[155,166]],"normalized":[{"db_name":"MESH","db_id":"D006327"}]},{"id":"22585","type":"Chemical","text":["trazodone"],"offsets":[[235,244]],"normalized":[{"db_name":"MESH","db_id":"D014196"}]}],"events":[],"coreferences":[],"relations":[{"id":"22586","type":"CID","arg1_id":"22582","arg2_id":"22581","normalized":[]},{"id":"22587","type":"CID","arg1_id":"22582","arg2_id":"22584","normalized":[]},{"id":"22588","type":"CID","arg1_id":"22583","arg2_id":"22581","normalized":[]},{"id":"22589","type":"CID","arg1_id":"22583","arg2_id":"22584","normalized":[]},{"id":"22590","type":"CID","arg1_id":"22585","arg2_id":"22581","normalized":[]},{"id":"22591","type":"CID","arg1_id":"22585","arg2_id":"22584","normalized":[]}]}
{"id":"22592","document_id":"3411101","passages":[{"id":"22593","type":"title","text":["Quinidine phenylethylbarbiturate-induced fulminant hepatitis in a pregnant woman. A case report."],"offsets":[[0,96]]},{"id":"22594","type":"abstract","text":["We report the case of a 19-year-old Laotian patient affected by fulminant hepatitis during the third trimester of her pregnancy after a 1-month administration of quinidine phenylethylbarbiturate. After delivery, the patient underwent orthotopic liver transplantation. The patient was in good condition 16 months after liver transplantation. Quinidine itself or phenylethylbarbiturate may be responsible for fulminant hepatitis in this patient."],"offsets":[[97,540]]}],"entities":[{"id":"22595","type":"Chemical","text":["Quinidine phenylethylbarbiturate"],"offsets":[[0,32]],"normalized":[{"db_name":"MESH","db_id":"C033457"}]},{"id":"22596","type":"Disease","text":["hepatitis"],"offsets":[[51,60]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"22597","type":"Disease","text":["hepatitis"],"offsets":[[171,180]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"22598","type":"Chemical","text":["quinidine phenylethylbarbiturate"],"offsets":[[259,291]],"normalized":[{"db_name":"MESH","db_id":"C033457"}]},{"id":"22599","type":"Chemical","text":["Quinidine"],"offsets":[[438,447]],"normalized":[{"db_name":"MESH","db_id":"D011802"}]},{"id":"22600","type":"Chemical","text":["phenylethylbarbiturate"],"offsets":[[458,480]],"normalized":[{"db_name":"MESH","db_id":"C033457"}]},{"id":"22601","type":"Disease","text":["hepatitis"],"offsets":[[514,523]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]}],"events":[],"coreferences":[],"relations":[{"id":"22602","type":"CID","arg1_id":"22595","arg2_id":"22596","normalized":[]},{"id":"22603","type":"CID","arg1_id":"22595","arg2_id":"22597","normalized":[]},{"id":"22604","type":"CID","arg1_id":"22595","arg2_id":"22601","normalized":[]},{"id":"22605","type":"CID","arg1_id":"22598","arg2_id":"22596","normalized":[]},{"id":"22606","type":"CID","arg1_id":"22598","arg2_id":"22597","normalized":[]},{"id":"22607","type":"CID","arg1_id":"22598","arg2_id":"22601","normalized":[]},{"id":"22608","type":"CID","arg1_id":"22600","arg2_id":"22596","normalized":[]},{"id":"22609","type":"CID","arg1_id":"22600","arg2_id":"22597","normalized":[]},{"id":"22610","type":"CID","arg1_id":"22600","arg2_id":"22601","normalized":[]}]}
{"id":"22611","document_id":"2598570","passages":[{"id":"22612","type":"title","text":["The epidemiology of the acute flank pain syndrome from suprofen."],"offsets":[[0,64]]},{"id":"22613","type":"abstract","text":["Suprofen, a new nonsteroidal anti-inflammatory drug, was marketed in early 1986 as an analgesic agent. Until physicians began reporting an unusual acute flank pain syndrome to the spontaneous reporting system, 700,000 persons used the drug in the United States. Through August 1986, a total of 163 cases of this syndrome were reported. To elucidate the epidemiology of the syndrome, a case-control study was performed, comparing 62 of the case patients who had been reported to the spontaneous reporting system to 185 suprofen-exposed control subjects who did not have the syndrome. Case patients were more likely to be men (odds ratio, 3.8; 95% confidence interval, 1.2-12.1), suffer from hay fever and asthma (odds ratio, 3.4; 95% confidence interval, 1.0-11.9); to participate in regular exercise (odds ratio, 5.9; 95% confidence interval, 1.1-30.7), especially in the use of Nautilus equipment (p = 0.02); and to use alcohol (odds ratio, 4.4; 95% confidence interval, 1.1-17.5). Possible risk factors included young age, concurrent use of other analgesic agents (especially ibuprofen), preexisting renal disease, a history of kidney stones, a history of gout, a recent increase in activity, a recent increase in sun exposure, and residence in the Sunbelt. These were findings that were suggestive but did not reach conventional statistical significance. These findings are consistent with the postulated mechanism for this unusual syndrome: acute diffuse crystallization of uric acid in renal tubules."],"offsets":[[65,1570]]}],"entities":[{"id":"22614","type":"Disease","text":["flank pain"],"offsets":[[30,40]],"normalized":[{"db_name":"MESH","db_id":"D021501"}]},{"id":"22615","type":"Chemical","text":["suprofen"],"offsets":[[55,63]],"normalized":[{"db_name":"MESH","db_id":"D013496"}]},{"id":"22616","type":"Chemical","text":["Suprofen"],"offsets":[[65,73]],"normalized":[{"db_name":"MESH","db_id":"D013496"}]},{"id":"22617","type":"Disease","text":["flank pain"],"offsets":[[218,228]],"normalized":[{"db_name":"MESH","db_id":"D021501"}]},{"id":"22618","type":"Chemical","text":["suprofen"],"offsets":[[583,591]],"normalized":[{"db_name":"MESH","db_id":"D013496"}]},{"id":"22619","type":"Disease","text":["hay fever"],"offsets":[[755,764]],"normalized":[{"db_name":"MESH","db_id":"D006255"}]},{"id":"22620","type":"Disease","text":["asthma"],"offsets":[[769,775]],"normalized":[{"db_name":"MESH","db_id":"D001249"}]},{"id":"22621","type":"Chemical","text":["alcohol"],"offsets":[[986,993]],"normalized":[{"db_name":"MESH","db_id":"D000431"}]},{"id":"22622","type":"Chemical","text":["ibuprofen"],"offsets":[[1143,1152]],"normalized":[{"db_name":"MESH","db_id":"D007052"}]},{"id":"22623","type":"Disease","text":["renal disease"],"offsets":[[1167,1180]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"22624","type":"Disease","text":["kidney stones"],"offsets":[[1195,1208]],"normalized":[{"db_name":"MESH","db_id":"D007669"}]},{"id":"22625","type":"Disease","text":["gout"],"offsets":[[1223,1227]],"normalized":[{"db_name":"MESH","db_id":"D006073"}]},{"id":"22626","type":"Chemical","text":["uric acid"],"offsets":[[1543,1552]],"normalized":[{"db_name":"MESH","db_id":"D014527"}]}],"events":[],"coreferences":[],"relations":[{"id":"22627","type":"CID","arg1_id":"22615","arg2_id":"22614","normalized":[]},{"id":"22628","type":"CID","arg1_id":"22615","arg2_id":"22617","normalized":[]},{"id":"22629","type":"CID","arg1_id":"22616","arg2_id":"22614","normalized":[]},{"id":"22630","type":"CID","arg1_id":"22616","arg2_id":"22617","normalized":[]},{"id":"22631","type":"CID","arg1_id":"22618","arg2_id":"22614","normalized":[]},{"id":"22632","type":"CID","arg1_id":"22618","arg2_id":"22617","normalized":[]}]}
{"id":"22633","document_id":"1415380","passages":[{"id":"22634","type":"title","text":["Hemolytic-uremic syndrome associated with ingestion of quinine."],"offsets":[[0,63]]},{"id":"22635","type":"abstract","text":["Hemolytic-uremic syndrome following quinine ingestion is a newly described phenomenon, with just two previous descriptions of 4 cases in the literature. We describe a 5th case. The reaction may be mediated by the presence of antibodies reactive against platelets in the presence of quinine. Treatment has included use of plasma exchange, prednisone, aspirin, and dipyridamole. The patients have all regained some degree of renal function. However, it is unclear whether pharmacological treatment or spontaneous resolution is responsible for the improvement. Quinine-associated hemolytic-uremic syndrome probably occurs more often than is recognized. It is important to recognize this reaction when it occurs and to avoid further quinine exposure, since the reaction seems to be recurrent."],"offsets":[[64,852]]}],"entities":[{"id":"22636","type":"Disease","text":["Hemolytic-uremic syndrome"],"offsets":[[0,25]],"normalized":[{"db_name":"MESH","db_id":"D006463"}]},{"id":"22637","type":"Chemical","text":["quinine"],"offsets":[[55,62]],"normalized":[{"db_name":"MESH","db_id":"D011803"}]},{"id":"22638","type":"Disease","text":["Hemolytic-uremic syndrome"],"offsets":[[64,89]],"normalized":[{"db_name":"MESH","db_id":"D006463"}]},{"id":"22639","type":"Chemical","text":["quinine"],"offsets":[[100,107]],"normalized":[{"db_name":"MESH","db_id":"D011803"}]},{"id":"22640","type":"Chemical","text":["quinine"],"offsets":[[346,353]],"normalized":[{"db_name":"MESH","db_id":"D011803"}]},{"id":"22641","type":"Chemical","text":["prednisone"],"offsets":[[402,412]],"normalized":[{"db_name":"MESH","db_id":"D011241"}]},{"id":"22642","type":"Chemical","text":["aspirin"],"offsets":[[414,421]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"22643","type":"Chemical","text":["dipyridamole"],"offsets":[[427,439]],"normalized":[{"db_name":"MESH","db_id":"D004176"}]},{"id":"22644","type":"Chemical","text":["Quinine"],"offsets":[[622,629]],"normalized":[{"db_name":"MESH","db_id":"D011803"}]},{"id":"22645","type":"Disease","text":["hemolytic-uremic syndrome"],"offsets":[[641,666]],"normalized":[{"db_name":"MESH","db_id":"D006463"}]},{"id":"22646","type":"Chemical","text":["quinine"],"offsets":[[793,800]],"normalized":[{"db_name":"MESH","db_id":"D011803"}]}],"events":[],"coreferences":[],"relations":[{"id":"22647","type":"CID","arg1_id":"22637","arg2_id":"22636","normalized":[]},{"id":"22648","type":"CID","arg1_id":"22637","arg2_id":"22638","normalized":[]},{"id":"22649","type":"CID","arg1_id":"22637","arg2_id":"22645","normalized":[]},{"id":"22650","type":"CID","arg1_id":"22639","arg2_id":"22636","normalized":[]},{"id":"22651","type":"CID","arg1_id":"22639","arg2_id":"22638","normalized":[]},{"id":"22652","type":"CID","arg1_id":"22639","arg2_id":"22645","normalized":[]},{"id":"22653","type":"CID","arg1_id":"22640","arg2_id":"22636","normalized":[]},{"id":"22654","type":"CID","arg1_id":"22640","arg2_id":"22638","normalized":[]},{"id":"22655","type":"CID","arg1_id":"22640","arg2_id":"22645","normalized":[]},{"id":"22656","type":"CID","arg1_id":"22644","arg2_id":"22636","normalized":[]},{"id":"22657","type":"CID","arg1_id":"22644","arg2_id":"22638","normalized":[]},{"id":"22658","type":"CID","arg1_id":"22644","arg2_id":"22645","normalized":[]},{"id":"22659","type":"CID","arg1_id":"22646","arg2_id":"22636","normalized":[]},{"id":"22660","type":"CID","arg1_id":"22646","arg2_id":"22638","normalized":[]},{"id":"22661","type":"CID","arg1_id":"22646","arg2_id":"22645","normalized":[]}]}
{"id":"22662","document_id":"1255900","passages":[{"id":"22663","type":"title","text":["Pyeloureteral filling defects associated with systemic anticoagulation: a case report."],"offsets":[[0,86]]},{"id":"22664","type":"abstract","text":["The etiology of pyeloureteritis cystica has long been attributed to chronic infection and inflammation. A case is presented that is unique in that the acute onset and the rapid resolution of pyeloureteral filling defects in this patient were documented by radiography. There is no evidence of antecedent or concurrent infection in this patient. The disease occurred subsequent to the initiation of heparin therapy for suspected pelvic thrombophlebitis and cleared rapidly subsequent to its discontinuation. The rate of resolution of the radiographic findings may be helpful in distinguishing between true pyeloureteritis cystica and submucosal hemorrhage."],"offsets":[[87,742]]}],"entities":[{"id":"22665","type":"Disease","text":["pyeloureteritis cystica"],"offsets":[[103,126]],"normalized":[{"db_name":"MESH","db_id":"D011702"}]},{"id":"22666","type":"Disease","text":["infection"],"offsets":[[163,172]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"22667","type":"Disease","text":["inflammation"],"offsets":[[177,189]],"normalized":[{"db_name":"MESH","db_id":"D007249"}]},{"id":"22668","type":"Disease","text":["infection"],"offsets":[[405,414]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"22669","type":"Chemical","text":["heparin"],"offsets":[[485,492]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"22670","type":"Disease","text":["thrombophlebitis"],"offsets":[[522,538]],"normalized":[{"db_name":"MESH","db_id":"D013924"}]},{"id":"22671","type":"Disease","text":["pyeloureteritis cystica"],"offsets":[[692,715]],"normalized":[{"db_name":"MESH","db_id":"D011702"}]},{"id":"22672","type":"Disease","text":["submucosal hemorrhage"],"offsets":[[720,741]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]}],"events":[],"coreferences":[],"relations":[{"id":"22673","type":"CID","arg1_id":"22669","arg2_id":"22665","normalized":[]},{"id":"22674","type":"CID","arg1_id":"22669","arg2_id":"22671","normalized":[]}]}
{"id":"22675","document_id":"85485","passages":[{"id":"22676","type":"title","text":["Changes in peroxisomes in preneoplastic liver and hepatoma of mice induced by alpha-benzene hexachloride."],"offsets":[[0,105]]},{"id":"22677","type":"abstract","text":["Peroxisomes in hepatomas and hyperplastic preneoplastic liver lesions induced in mice by 500 ppm alpha-benzene hexachloride were examined histochemically and electron microscopically. Although most of the hepatomas were well-differentiated tumors and contained a considerable number of peroxisomes, the tumor cells did not respond to ethyl-alpha-p-chlorophenoxyisobutyrate with proliferation of peroxisomes. At the 16th week of carcinogen feeding, hyperplastic nodules appeared and advanced to further stages. A majority of the nodules showed a considerable number of peroxisomes and the inductive proliferation of peroxisomes. Within the nodules, foci of proliferation of the cells that showed no inducibility of proliferation of peroxisomes appeared. These cells proliferated further, replacing the most part of the nodules, and with this process hepatomas appeared to have been formed. No abnormal matrical inclusions of peroxisomes were formed in the cells of hyperplastic nodules by ethyl-alpha-p-chlorophenoxyisobutyrate unlike in the case of rats."],"offsets":[[106,1160]]}],"entities":[{"id":"22678","type":"Disease","text":["hepatoma"],"offsets":[[50,58]],"normalized":[{"db_name":"MESH","db_id":"D006528"}]},{"id":"22679","type":"Chemical","text":["alpha-benzene hexachloride"],"offsets":[[78,104]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"22680","type":"Disease","text":["hepatomas"],"offsets":[[121,130]],"normalized":[{"db_name":"MESH","db_id":"D006528"}]},{"id":"22681","type":"Disease","text":["liver lesions"],"offsets":[[162,175]],"normalized":[{"db_name":"MESH","db_id":"D017093"}]},{"id":"22682","type":"Chemical","text":["alpha-benzene hexachloride"],"offsets":[[203,229]],"normalized":[{"db_name":"MESH","db_id":"D001556"}]},{"id":"22683","type":"Disease","text":["hepatomas"],"offsets":[[311,320]],"normalized":[{"db_name":"MESH","db_id":"D006528"}]},{"id":"22684","type":"Disease","text":["tumors"],"offsets":[[346,352]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"22685","type":"Disease","text":["tumor"],"offsets":[[409,414]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"22686","type":"Chemical","text":["ethyl-alpha-p-chlorophenoxyisobutyrate"],"offsets":[[440,478]],"normalized":[{"db_name":"MESH","db_id":"C012282"}]},{"id":"22687","type":"Disease","text":["hepatomas"],"offsets":[[955,964]],"normalized":[{"db_name":"MESH","db_id":"D006528"}]},{"id":"22688","type":"Chemical","text":["ethyl-alpha-p-chlorophenoxyisobutyrate"],"offsets":[[1094,1132]],"normalized":[{"db_name":"MESH","db_id":"C012282"}]}],"events":[],"coreferences":[],"relations":[{"id":"22689","type":"CID","arg1_id":"22679","arg2_id":"22678","normalized":[]},{"id":"22690","type":"CID","arg1_id":"22679","arg2_id":"22680","normalized":[]},{"id":"22691","type":"CID","arg1_id":"22679","arg2_id":"22683","normalized":[]},{"id":"22692","type":"CID","arg1_id":"22679","arg2_id":"22687","normalized":[]},{"id":"22693","type":"CID","arg1_id":"22682","arg2_id":"22678","normalized":[]},{"id":"22694","type":"CID","arg1_id":"22682","arg2_id":"22680","normalized":[]},{"id":"22695","type":"CID","arg1_id":"22682","arg2_id":"22683","normalized":[]},{"id":"22696","type":"CID","arg1_id":"22682","arg2_id":"22687","normalized":[]}]}
{"id":"22697","document_id":"48362","passages":[{"id":"22698","type":"title","text":["Quinidine hepatitis."],"offsets":[[0,20]]},{"id":"22699","type":"abstract","text":["Long-term administration of quinidine was associated with persistent elevation of serum concentrations of SGOT, lactic acid dehydrogenase, and alkaline phosphatase. Liver biopsy showed active hepatitis. Discontinuance of quinidine therapy led to normalization of liver function tests. A challenge dose of quinidine caused clinical symptoms and abrupt elevation of SGOT, alkaline phosphatase, and lactic acid dehydrogenase values. We concluded that this patient had quinidine hepatotoxicity and believe that this is the first case reported with liver biopsy documentation. This report also suggests that, even after long-term administration, the hepatic toxicity is reversible."],"offsets":[[21,697]]}],"entities":[{"id":"22700","type":"Chemical","text":["Quinidine"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D011802"}]},{"id":"22701","type":"Disease","text":["hepatitis"],"offsets":[[10,19]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"22702","type":"Chemical","text":["quinidine"],"offsets":[[49,58]],"normalized":[{"db_name":"MESH","db_id":"D011802"}]},{"id":"22703","type":"Chemical","text":["lactic acid"],"offsets":[[133,144]],"normalized":[{"db_name":"MESH","db_id":"D019344"}]},{"id":"22704","type":"Disease","text":["hepatitis"],"offsets":[[213,222]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"22705","type":"Chemical","text":["quinidine"],"offsets":[[242,251]],"normalized":[{"db_name":"MESH","db_id":"D011802"}]},{"id":"22706","type":"Chemical","text":["quinidine"],"offsets":[[326,335]],"normalized":[{"db_name":"MESH","db_id":"D011802"}]},{"id":"22707","type":"Chemical","text":["lactic acid"],"offsets":[[417,428]],"normalized":[{"db_name":"MESH","db_id":"D019344"}]},{"id":"22708","type":"Chemical","text":["quinidine"],"offsets":[[486,495]],"normalized":[{"db_name":"MESH","db_id":"D011802"}]},{"id":"22709","type":"Disease","text":["hepatotoxicity"],"offsets":[[496,510]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"22710","type":"Disease","text":["hepatic toxicity"],"offsets":[[666,682]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]}],"events":[],"coreferences":[],"relations":[{"id":"22711","type":"CID","arg1_id":"22700","arg2_id":"22701","normalized":[]},{"id":"22712","type":"CID","arg1_id":"22700","arg2_id":"22704","normalized":[]},{"id":"22713","type":"CID","arg1_id":"22700","arg2_id":"22709","normalized":[]},{"id":"22714","type":"CID","arg1_id":"22700","arg2_id":"22710","normalized":[]},{"id":"22715","type":"CID","arg1_id":"22702","arg2_id":"22701","normalized":[]},{"id":"22716","type":"CID","arg1_id":"22702","arg2_id":"22704","normalized":[]},{"id":"22717","type":"CID","arg1_id":"22702","arg2_id":"22709","normalized":[]},{"id":"22718","type":"CID","arg1_id":"22702","arg2_id":"22710","normalized":[]},{"id":"22719","type":"CID","arg1_id":"22705","arg2_id":"22701","normalized":[]},{"id":"22720","type":"CID","arg1_id":"22705","arg2_id":"22704","normalized":[]},{"id":"22721","type":"CID","arg1_id":"22705","arg2_id":"22709","normalized":[]},{"id":"22722","type":"CID","arg1_id":"22705","arg2_id":"22710","normalized":[]},{"id":"22723","type":"CID","arg1_id":"22706","arg2_id":"22701","normalized":[]},{"id":"22724","type":"CID","arg1_id":"22706","arg2_id":"22704","normalized":[]},{"id":"22725","type":"CID","arg1_id":"22706","arg2_id":"22709","normalized":[]},{"id":"22726","type":"CID","arg1_id":"22706","arg2_id":"22710","normalized":[]},{"id":"22727","type":"CID","arg1_id":"22708","arg2_id":"22701","normalized":[]},{"id":"22728","type":"CID","arg1_id":"22708","arg2_id":"22704","normalized":[]},{"id":"22729","type":"CID","arg1_id":"22708","arg2_id":"22709","normalized":[]},{"id":"22730","type":"CID","arg1_id":"22708","arg2_id":"22710","normalized":[]}]}
{"id":"22731","document_id":"9067481","passages":[{"id":"22732","type":"title","text":["Cholesteryl hemisuccinate treatment protects rodents from the toxic effects of acetaminophen, adriamycin, carbon tetrachloride, chloroform and galactosamine."],"offsets":[[0,157]]},{"id":"22733","type":"abstract","text":["In addition to its use as a stabilizer\/rigidifier of membranes, cholesteryl hemisuccinate, tris salt (CS) administration has also been shown to protect rats from the hepatotoxic effects of carbon tetrachloride (CCl4). To further our understanding of the mechanism of CS cytoprotection, we examined in rats and mice the protective abilities of CS and the non-hydrolyzable ether form of CS, gamma-cholesteryloxybutyric acid, tris salt (CSE) against acetaminophen-, adriamycin-, carbon tetrachloride-, chloroform- and galactosamine-induced toxicity. The results of these studies demonstrated that CS-mediated protection is not selective for a particular species, organ system or toxic chemical. A 24-h pretreatment of both rats and mice with a single dose of CS (100mg\/kg, i.p.), resulted in significant protection against the hepatotoxic effects of CCl4, CHCl3, acetaminophen and galactosamine and against the lethal (and presumably cardiotoxic) effect of adriamycin administration. Maximal CS-mediated protection was observed in experimental animals pretreated 24 h prior to the toxic insult. These data suggest that CS intervenes in a critical cellular event that is an important common pathway to toxic cell death. The mechanism of CS protection does not appear to be dependent on the inhibition of chemical bioactivation to a toxic reactive intermediate (in light of the protection observed against galactosamine hepatotoxicity). However, based on the data presented, we can not exclude the possibility that CS administration inhibits chemical bioactivation. Our findings do suggest that CS-mediated protection is dependent on the action of the intact anionic CS molecule (non-hydrolyzable CSE was as protective as CS), whose mechanism has yet to be defined."],"offsets":[[158,1918]]}],"entities":[{"id":"22734","type":"Chemical","text":["Cholesteryl hemisuccinate"],"offsets":[[0,25]],"normalized":[{"db_name":"MESH","db_id":"C013440"}]},{"id":"22735","type":"Chemical","text":["acetaminophen"],"offsets":[[79,92]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"22736","type":"Chemical","text":["adriamycin"],"offsets":[[94,104]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"22737","type":"Chemical","text":["carbon tetrachloride"],"offsets":[[106,126]],"normalized":[{"db_name":"MESH","db_id":"D002251"}]},{"id":"22738","type":"Chemical","text":["chloroform"],"offsets":[[128,138]],"normalized":[{"db_name":"MESH","db_id":"D002725"}]},{"id":"22739","type":"Chemical","text":["galactosamine"],"offsets":[[143,156]],"normalized":[{"db_name":"MESH","db_id":"D005688"}]},{"id":"22740","type":"Chemical","text":["cholesteryl hemisuccinate"],"offsets":[[222,247]],"normalized":[{"db_name":"MESH","db_id":"C013440"}]},{"id":"22741","type":"Chemical","text":["tris salt"],"offsets":[[249,258]],"normalized":[]},{"id":"22742","type":"Chemical","text":["CS"],"offsets":[[260,262]],"normalized":[]},{"id":"22743","type":"Disease","text":["hepatotoxic"],"offsets":[[324,335]],"normalized":[{"db_name":"MESH","db_id":"D056486"}]},{"id":"22744","type":"Chemical","text":["carbon tetrachloride"],"offsets":[[347,367]],"normalized":[{"db_name":"MESH","db_id":"D002251"}]},{"id":"22745","type":"Chemical","text":["CCl4"],"offsets":[[369,373]],"normalized":[{"db_name":"MESH","db_id":"D002251"}]},{"id":"22746","type":"Chemical","text":["CS"],"offsets":[[425,427]],"normalized":[]},{"id":"22747","type":"Chemical","text":["CS"],"offsets":[[501,503]],"normalized":[]},{"id":"22748","type":"Chemical","text":["CS"],"offsets":[[543,545]],"normalized":[]},{"id":"22749","type":"Chemical","text":["gamma-cholesteryloxybutyric acid"],"offsets":[[547,579]],"normalized":[{"db_name":"MESH","db_id":"C103872"}]},{"id":"22750","type":"Chemical","text":["tris salt"],"offsets":[[581,590]],"normalized":[]},{"id":"22751","type":"Chemical","text":["CSE"],"offsets":[[592,595]],"normalized":[]},{"id":"22752","type":"Chemical","text":["acetaminophen"],"offsets":[[605,618]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"22753","type":"Chemical","text":["adriamycin"],"offsets":[[621,631]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"22754","type":"Chemical","text":["carbon 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{"id":"22825","document_id":"19274460","passages":[{"id":"22826","type":"title","text":["DSMM XI study: dose definition for intravenous cyclophosphamide in combination with bortezomib\/dexamethasone for remission induction in patients with newly diagnosed myeloma."],"offsets":[[0,174]]},{"id":"22827","type":"abstract","text":["A clinical trial was initiated to evaluate the recommended dose of cyclophosphamide in combination with bortezomib and dexamethasone as induction treatment before stem cell transplantation for younger patients with newly diagnosed multiple myeloma (MM). Thirty patients were treated with three 21-day cycles of bortezomib 1.3 mg\/m(2) on days 1, 4, 8, and 11 plus dexamethasone 40 mg on the day of bortezomib injection and the day after plus cyclophosphamide at 900, 1,200, or 1,500 mg\/m(2) on day 1. The maximum tolerated dose of cyclophosphamide was defined as 900 mg\/m(2). At this dose level, 92% of patients achieved at least a partial response. The overall response rate [complete response (CR) plus partial response (PR)] across all dose levels was 77%, with a 10% CR rate. No patient experienced progressive disease. The most frequent adverse events were hematological and gastrointestinal toxicities as well as neuropathy. The results suggest that bortezomib in combination with cyclophosphamide at 900 mg\/m(2) and dexamethasone is an effective induction treatment for patients with newly diagnosed MM that warrants further investigation."],"offsets":[[175,1320]]}],"entities":[{"id":"22828","type":"Chemical","text":["cyclophosphamide"],"offsets":[[47,63]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"22829","type":"Chemical","text":["bortezomib"],"offsets":[[84,94]],"normalized":[{"db_name":"MESH","db_id":"C400082"}]},{"id":"22830","type":"Chemical","text":["dexamethasone"],"offsets":[[95,108]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"22831","type":"Disease","text":["myeloma"],"offsets":[[166,173]],"normalized":[{"db_name":"MESH","db_id":"D009101"}]},{"id":"22832","type":"Chemical","text":["cyclophosphamide"],"offsets":[[242,258]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"22833","type":"Chemical","text":["bortezomib"],"offsets":[[279,289]],"normalized":[{"db_name":"MESH","db_id":"C400082"}]},{"id":"22834","type":"Chemical","text":["dexamethasone"],"offsets":[[294,307]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"22835","type":"Disease","text":["multiple myeloma"],"offsets":[[406,422]],"normalized":[{"db_name":"MESH","db_id":"D009101"}]},{"id":"22836","type":"Disease","text":["MM"],"offsets":[[424,426]],"normalized":[{"db_name":"MESH","db_id":"D009101"}]},{"id":"22837","type":"Chemical","text":["bortezomib"],"offsets":[[486,496]],"normalized":[{"db_name":"MESH","db_id":"C400082"}]},{"id":"22838","type":"Chemical","text":["dexamethasone"],"offsets":[[538,551]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"22839","type":"Chemical","text":["bortezomib"],"offsets":[[572,582]],"normalized":[{"db_name":"MESH","db_id":"C400082"}]},{"id":"22840","type":"Chemical","text":["cyclophosphamide"],"offsets":[[616,632]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"22841","type":"Chemical","text":["cyclophosphamide"],"offsets":[[705,721]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"22842","type":"Disease","text":["hematological and gastrointestinal toxicities"],"offsets":[[1036,1081]],"normalized":[{"db_name":"MESH","db_id":"D006402"},{"db_name":"MESH","db_id":"D005767"}]},{"id":"22843","type":"Disease","text":["hematological","toxicities"],"offsets":[[1036,1049],[1071,1081]],"normalized":[{"db_name":"MESH","db_id":"D006402"}]},{"id":"22844","type":"Disease","text":["gastrointestinal toxicities"],"offsets":[[1054,1081]],"normalized":[{"db_name":"MESH","db_id":"D005767"}]},{"id":"22845","type":"Disease","text":["neuropathy"],"offsets":[[1093,1103]],"normalized":[{"db_name":"MESH","db_id":"D009422"}]},{"id":"22846","type":"Chemical","text":["bortezomib"],"offsets":[[1130,1140]],"normalized":[{"db_name":"MESH","db_id":"C400082"}]},{"id":"22847","type":"Chemical","text":["cyclophosphamide"],"offsets":[[1161,1177]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"22848","type":"Chemical","text":["dexamethasone"],"offsets":[[1197,1210]],"normalized":[{"db_name":"MESH","db_id":"D003907"}]},{"id":"22849","type":"Disease","text":["MM"],"offsets":[[1281,1283]],"normalized":[{"db_name":"MESH","db_id":"D009101"}]}],"events":[],"coreferences":[],"relations":[{"id":"22850","type":"CID","arg1_id":"22830","arg2_id":"22842","normalized":[]},{"id":"22851","type":"CID","arg1_id":"22830","arg2_id":"22843","normalized":[]},{"id":"22852","type":"CID","arg1_id":"22834","arg2_id":"22842","normalized":[]},{"id":"22853","type":"CID","arg1_id":"22834","arg2_id":"22843","normalized":[]},{"id":"22854","type":"CID","arg1_id":"22838","arg2_id":"22842","normalized":[]},{"id":"22855","type":"CID","arg1_id":"22838","arg2_id":"22843","normalized":[]},{"id":"22856","type":"CID","arg1_id":"22848","arg2_id":"22842","normalized":[]},{"id":"22857","type":"CID","arg1_id":"22848","arg2_id":"22843","normalized":[]},{"id":"22858","type":"CID","arg1_id":"22829","arg2_id":"22842","normalized":[]},{"id":"22859","type":"CID","arg1_id":"22829","arg2_id":"22844","normalized":[]},{"id":"22860","type":"CID","arg1_id":"22833","arg2_id":"22842","normalized":[]},{"id":"22861","type":"CID","arg1_id":"22833","arg2_id":"22844","normalized":[]},{"id":"22862","type":"CID","arg1_id":"22837","arg2_id":"22842","normalized":[]},{"id":"22863","type":"CID","arg1_id":"22837","arg2_id":"22844","normalized":[]},{"id":"22864","type":"CID","arg1_id":"22839","arg2_id":"22842","normalized":[]},{"id":"22865","type":"CID","arg1_id":"22839","arg2_id":"22844","normalized":[]},{"id":"22866","type":"CID","arg1_id":"22846","arg2_id":"22842","normalized":[]},{"id":"22867","type":"CID","arg1_id":"22846","arg2_id":"22844","normalized":[]},{"id":"22868","type":"CID","arg1_id":"22828","arg2_id":"22842","normalized":[]},{"id":"22869","type":"CID","arg1_id":"22828","arg2_id":"22843","normalized":[]},{"id":"22870","type":"CID","arg1_id":"22832","arg2_id":"22842","normalized":[]},{"id":"22871","type":"CID","arg1_id":"22832","arg2_id":"22843","normalized":[]},{"id":"22872","type":"CID","arg1_id":"22840","arg2_id":"22842","normalized":[]},{"id":"22873","type":"CID","arg1_id":"22840","arg2_id":"22843","normalized":[]},{"id":"22874","type":"CID","arg1_id":"22841","arg2_id":"22842","normalized":[]},{"id":"22875","type":"CID","arg1_id":"22841","arg2_id":"22843","normalized":[]},{"id":"22876","type":"CID","arg1_id":"22847","arg2_id":"22842","normalized":[]},{"id":"22877","type":"CID","arg1_id":"22847","arg2_id":"22843","normalized":[]},{"id":"22878","type":"CID","arg1_id":"22830","arg2_id":"22842","normalized":[]},{"id":"22879","type":"CID","arg1_id":"22830","arg2_id":"22844","normalized":[]},{"id":"22880","type":"CID","arg1_id":"22834","arg2_id":"22842","normalized":[]},{"id":"22881","type":"CID","arg1_id":"22834","arg2_id":"22844","normalized":[]},{"id":"22882","type":"CID","arg1_id":"22838","arg2_id":"22842","normalized":[]},{"id":"22883","type":"CID","arg1_id":"22838","arg2_id":"22844","normalized":[]},{"id":"22884","type":"CID","arg1_id":"22848","arg2_id":"22842","normalized":[]},{"id":"22885","type":"CID","arg1_id":"22848","arg2_id":"22844","normalized":[]},{"id":"22886","type":"CID","arg1_id":"22829","arg2_id":"22845","normalized":[]},{"id":"22887","type":"CID","arg1_id":"22833","arg2_id":"22845","normalized":[]},{"id":"22888","type":"CID","arg1_id":"22837","arg2_id":"22845","normalized":[]},{"id":"22889","type":"CID","arg1_id":"22839","arg2_id":"22845","normalized":[]},{"id":"22890","type":"CID","arg1_id":"22846","arg2_id":"22845","normalized":[]},{"id":"22891","type":"CID","arg1_id":"22828","arg2_id":"22842","normalized":[]},{"id":"22892","type":"CID","arg1_id":"22828","arg2_id":"22844","normalized":[]},{"id":"22893","type":"CID","arg1_id":"22832","arg2_id":"22842","normalized":[]},{"id":"22894","type":"CID","arg1_id":"22832","arg2_id":"22844","normalized":[]},{"id":"22895","type":"CID","arg1_id":"22840","arg2_id":"22842","normalized":[]},{"id":"22896","type":"CID","arg1_id":"22840","arg2_id":"22844","normalized":[]},{"id":"22897","type":"CID","arg1_id":"22841","arg2_id":"22842","normalized":[]},{"id":"22898","type":"CID","arg1_id":"22841","arg2_id":"22844","normalized":[]},{"id":"22899","type":"CID","arg1_id":"22847","arg2_id":"22842","normalized":[]},{"id":"22900","type":"CID","arg1_id":"22847","arg2_id":"22844","normalized":[]},{"id":"22901","type":"CID","arg1_id":"22829","arg2_id":"22842","normalized":[]},{"id":"22902","type":"CID","arg1_id":"22829","arg2_i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{"id":"22920","document_id":"18201582","passages":[{"id":"22921","type":"title","text":["Results of a comparative, phase III, 12-week, multicenter, prospective, randomized, double-blind assessment of the efficacy and tolerability of a fixed-dose combination of telmisartan and amlodipine versus amlodipine monotherapy in Indian adults with stage II hypertension."],"offsets":[[0,273]]},{"id":"22922","type":"abstract","text":["OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerability of a new fixed-dose combination (FDC) of telmisartan 40 mg + amlodipine 5 mg (T+A) compared with amlodipine 5-mg monotherapy (A) in adult Indian patients with stage II hypertension. METHODS: This comparative, Phase III, 12-week, multicenter, prospective, randomized, double-blind study was conducted in Indian patients aged 18 to 65 years with established stage II hypertension. Patients were treated with oral FDC of T+A or A QD before breakfast for 12 weeks; blood pressure (BP) and heart rate were measured in the sitting position. Primary efficacy end points were reduction in clinical systolic BP (SBP)\/ diastolic BP (DBP) from baseline to study end and number of responders (ie, patients who achieved target SBP\/ DBP <130\/<80 mm Hg) at end of study. Tolerability was assessed by treatment-emergent adverse events, identified using physical examination, laboratory analysis, and electrocardiography. RESULTS: A total of 210 patients were enrolled in the study; 203 patients (143 men, 60 women) completed the study while 7 were lost to follow-up (4 patients in the T+A group and 3 in the A group) and considered with-drawn. At study end, statistically significant percentage reductions from baseline within groups and between groups were observed in SBP (T+A [-27.4%]; A [-16.6%]) and DBP (T+A [-20.1%]; A [-13.3%]) (all, P < 0.05). Response rates were 87.3% (89\/102) in the T+A group and 69.3% (70\/101) in the A group (P < 0.05). The prevalences of adverse events were not significantly different between the 2 treatment groups (T+A, 16.0% [17\/106]; A, 15.4% [16\/104]). Peripheral edema was reported in 8.5% patients (9\/106) in the T+A group compared with 13.5% (14\/104) in the A group, and cough was reported in 3.8% patients (4\/106) in the T+A group and 1.0% (1\/104) patients in the A group; these differences did not reach statistical significance. The incidences of headache, dizziness, and diarrhea were similar between the 2 groups. CONCLUSIONS: Among these Indian patients with stage II hypertension, the FDC of T+A was found to be significantly more effective, with regard to BP reductions, than A, and both treatments were well tolerated."],"offsets":[[274,2505]]}],"entities":[{"id":"22923","type":"Chemical","text":["telmisartan"],"offsets":[[172,183]],"normalized":[{"db_name":"MESH","db_id":"C084178"}]},{"id":"22924","type":"Chemical","text":["amlodipine"],"offsets":[[188,198]],"normalized":[{"db_name":"MESH","db_id":"D017311"}]},{"id":"22925","type":"Chemical","text":["amlodipine"],"offsets":[[206,216]],"normalized":[{"db_name":"MESH","db_id":"D017311"}]},{"id":"22926","type":"Disease","text":["hypertension"],"offsets":[[260,272]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"22927","type":"Chemical","text":["telmisartan"],"offsets":[[394,405]],"normalized":[{"db_name":"MESH","db_id":"C084178"}]},{"id":"22928","type":"Chemical","text":["amlodipine"],"offsets":[[414,424]],"normalized":[{"db_name":"MESH","db_id":"D017311"}]},{"id":"22929","type":"Chemical","text":["amlodipine"],"offsets":[[450,460]],"normalized":[{"db_name":"MESH","db_id":"D017311"}]},{"id":"22930","type":"Disease","text":["hypertension"],"offsets":[[521,533]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"22931","type":"Disease","text":["hypertension"],"offsets":[[718,730]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"22932","type":"Disease","text":["edema"],"offsets":[[1939,1944]],"normalized":[{"db_name":"MESH","db_id":"D004487"}]},{"id":"22933","type":"Disease","text":["cough"],"offsets":[[2049,2054]],"normalized":[{"db_name":"MESH","db_id":"D003371"}]},{"id":"22934","type":"Disease","text":["headache"],"offsets":[[2228,2236]],"normalized":[{"db_name":"MESH","db_id":"D006261"}]},{"id":"22935","type":"Disease","text":["dizziness"],"offsets":[[2238,2247]],"normalized":[{"db_name":"MESH","db_id":"D004244"}]},{"id":"22936","type":"Disease","text":["diarrhea"],"offsets":[[2253,2261]],"normalized":[{"db_name":"MESH","db_id":"D003967"}]},{"id":"22937","type":"Disease","text":["hypertension"],"offsets":[[2352,2364]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]}],"events":[],"coreferences":[],"relations":[{"id":"22938","type":"CID","arg1_id":"22924","arg2_id":"22934","normalized":[]},{"id":"22939","type":"CID","arg1_id":"22925","arg2_id":"22934","normalized":[]},{"id":"22940","type":"CID","arg1_id":"22928","arg2_id":"22934","normalized":[]},{"id":"22941","type":"CID","arg1_id":"22929","arg2_id":"22934","normalized":[]},{"id":"22942","type":"CID","arg1_id":"22923","arg2_id":"22935","normalized":[]},{"id":"22943","type":"CID","arg1_id":"22927","arg2_id":"22935","normalized":[]},{"id":"22944","type":"CID","arg1_id":"22923","arg2_id":"22934","normalized":[]},{"id":"22945","type":"CID","arg1_id":"22927","arg2_id":"22934","normalized":[]},{"id":"22946","type":"CID","arg1_id":"22923","arg2_id":"22936","normalized":[]},{"id":"22947","type":"CID","arg1_id":"22927","arg2_id":"22936","normalized":[]},{"id":"22948","type":"CID","arg1_id":"22923","arg2_id":"22932","normalized":[]},{"id":"22949","type":"CID","arg1_id":"22927","arg2_id":"22932","normalized":[]},{"id":"22950","type":"CID","arg1_id":"22924","arg2_id":"22936","normalized":[]},{"id":"22951","type":"CID","arg1_id":"22925","arg2_id":"22936","normalized":[]},{"id":"22952","type":"CID","arg1_id":"22928","arg2_id":"22936","normalized":[]},{"id":"22953","type":"CID","arg1_id":"22929","arg2_id":"22936","normalized":[]},{"id":"22954","type":"CID","arg1_id":"22924","arg2_id":"22932","normalized":[]},{"id":"22955","type":"CID","arg1_id":"22925","arg2_id":"22932","normalized":[]},{"id":"22956","type":"CID","arg1_id":"22928","arg2_id":"22932","normalized":[]},{"id":"22957","type":"CID","arg1_id":"22929","arg2_id":"22932","normalized":[]},{"id":"22958","type":"CID","arg1_id":"22924","arg2_id":"22933","normalized":[]},{"id":"22959","type":"CID","arg1_id":"22925","arg2_id":"22933","normalized":[]},{"id":"22960","type":"CID","arg1_id":"22928","arg2_id":"22933","normalized":[]},{"id":"22961","type":"CID","arg1_id":"22929","arg2_id":"22933","normalized":[]},{"id":"22962","type":"CID","arg1_id":"22924","arg2_id":"22935","normalized":[]},{"id":"22963","type":"CID","arg1_id":"22925","arg2_id":"22935","normalized":[]},{"id":"22964","type":"CID","arg1_id":"22928","arg2_id":"22935","normalized":[]},{"id":"22965","type":"CID","arg1_id":"22929","arg2_id":"22935","normalized":[]},{"id":"22966","type":"CID","arg1_id":"22923","arg2_id":"22933","normalized":[]},{"id":"22967","type":"CID","arg1_id":"22927","arg2_id":"22933","normalized":[]}]}
{"id":"22968","document_id":"11337188","passages":[{"id":"22969","type":"title","text":["Cutaneous leucocytoclastic vasculitis associated with oxacillin."],"offsets":[[0,64]]},{"id":"22970","type":"abstract","text":["A 67-year-old man who was treated with oxacillin for one week because of Staphylococcus aureus bacteremia, developed renal failure and diffuse, symmetric, palpable purpuric lesions on his feet. Necrotic blisters were noted on his fingers. Skin biopsies showed findings diagnostic of leucocytoclastic vasculitis. Oxacillin was discontinued and patient was treated with corticosteroids. The rash disappeared after three weeks and renal function returned to normal. Leucocytoclastic vasculitis presents as palpable purpura of the lower extremities often accompanied by abdominal pain, arthralgia, and renal involvement. Etiologic factors or associated disorders include infections, medications, collagen vascular disease and neoplasia. However, in half of the cases no etiologic factor is identified. Usually it is a self-limited disorder, but corticosteroid therapy may be needed in life-threatening cases since early treatment with corticosteroids in severe cases can prevent complications. Oxacillin should be included among the drugs that can cause leucocytoclastic vasculitis."],"offsets":[[65,1143]]}],"entities":[{"id":"22971","type":"Disease","text":["Cutaneous leucocytoclastic vasculitis"],"offsets":[[0,37]],"normalized":[{"db_name":"MESH","db_id":"D018366"}]},{"id":"22972","type":"Chemical","text":["oxacillin"],"offsets":[[54,63]],"normalized":[{"db_name":"MESH","db_id":"D010068"}]},{"id":"22973","type":"Chemical","text":["oxacillin"],"offsets":[[104,113]],"normalized":[{"db_name":"MESH","db_id":"D010068"}]},{"id":"22974","type":"Disease","text":["Staphylococcus aureus bacteremia"],"offsets":[[138,170]],"normalized":[{"db_name":"MESH","db_id":"D013203"},{"db_name":"MESH","db_id":"D016470"}]},{"id":"22975","type":"Disease","text":["Staphylococcus aureus bacteremia"],"offsets":[[138,170]],"normalized":[{"db_name":"MESH","db_id":"D013203"}]},{"id":"22976","type":"Disease","text":["bacteremia"],"offsets":[[160,170]],"normalized":[{"db_name":"MESH","db_id":"D016470"}]},{"id":"22977","type":"Disease","text":["renal failure"],"offsets":[[182,195]],"normalized":[{"db_name":"MESH","db_id":"D051437"}]},{"id":"22978","type":"Disease","text":["purpuric lesions"],"offsets":[[229,245]],"normalized":[{"db_name":"MESH","db_id":"D011693"}]},{"id":"22979","type":"Disease","text":["Necrotic blisters"],"offsets":[[259,276]],"normalized":[{"db_name":"MESH","db_id":"D009336"},{"db_name":"MESH","db_id":"D001768"}]},{"id":"22980","type":"Disease","text":["Necrotic"],"offsets":[[259,267]],"normalized":[{"db_name":"MESH","db_id":"D009336"}]},{"id":"22981","type":"Disease","text":["blisters"],"offsets":[[268,276]],"normalized":[{"db_name":"MESH","db_id":"D001768"}]},{"id":"22982","type":"Disease","text":["leucocytoclastic vasculitis"],"offsets":[[348,375]],"normalized":[{"db_name":"MESH","db_id":"D018366"}]},{"id":"22983","type":"Chemical","text":["Oxacillin"],"offsets":[[377,386]],"normalized":[{"db_name":"MESH","db_id":"D010068"}]},{"id":"22984","type":"Chemical","text":["corticosteroids"],"offsets":[[433,448]],"normalized":[{"db_name":"MESH","db_id":"D000305"}]},{"id":"22985","type":"Disease","text":["rash"],"offsets":[[454,458]],"normalized":[{"db_name":"MESH","db_id":"D005076"}]},{"id":"22986","type":"Disease","text":["Leucocytoclastic vasculitis"],"offsets":[[528,555]],"normalized":[{"db_name":"MESH","db_id":"D018366"}]},{"id":"22987","type":"Disease","text":["purpura"],"offsets":[[577,584]],"normalized":[{"db_name":"MESH","db_id":"D011693"}]},{"id":"22988","type":"Disease","text":["abdominal pain"],"offsets":[[631,645]],"normalized":[{"db_name":"MESH","db_id":"D015746"}]},{"id":"22989","type":"Disease","text":["arthralgia"],"offsets":[[647,657]],"normalized":[{"db_name":"MESH","db_id":"D018771"}]},{"id":"22990","type":"Disease","text":["renal involvement"],"offsets":[[663,680]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"22991","type":"Disease","text":["infections"],"offsets":[[732,742]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"22992","type":"Disease","text":["collagen vascular disease"],"offsets":[[757,782]],"normalized":[{"db_name":"MESH","db_id":"D003095"}]},{"id":"22993","type":"Disease","text":["neoplasia"],"offsets":[[787,796]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"22994","type":"Chemical","text":["corticosteroid"],"offsets":[[906,920]],"normalized":[{"db_name":"MESH","db_id":"D000305"}]},{"id":"22995","type":"Chemical","text":["corticosteroids"],"offsets":[[996,1011]],"normalized":[{"db_name":"MESH","db_id":"D000305"}]},{"id":"22996","type":"Chemical","text":["Oxacillin"],"offsets":[[1055,1064]],"normalized":[{"db_name":"MESH","db_id":"D010068"}]},{"id":"22997","type":"Disease","text":["leucocytoclastic vasculitis"],"offsets":[[1115,1142]],"normalized":[{"db_name":"MESH","db_id":"D018366"}]}],"events":[],"coreferences":[],"relations":[{"id":"22998","type":"CID","arg1_id":"22984","arg2_id":"22977","normalized":[]},{"id":"22999","type":"CID","arg1_id":"22994","arg2_id":"22977","normalized":[]},{"id":"23000","type":"CID","arg1_id":"22995","arg2_id":"22977","normalized":[]},{"id":"23001","type":"CID","arg1_id":"22972","arg2_id":"22977","normalized":[]},{"id":"23002","type":"CID","arg1_id":"22973","arg2_id":"22977","normalized":[]},{"id":"23003","type":"CID","arg1_id":"22983","arg2_id":"22977","normalized":[]},{"id":"23004","type":"CID","arg1_id":"22996","arg2_id":"22977","normalized":[]},{"id":"23005","type":"CID","arg1_id":"22972","arg2_id":"22971","normalized":[]},{"id":"23006","type":"CID","arg1_id":"22972","arg2_id":"22982","normalized":[]},{"id":"23007","type":"CID","arg1_id":"22972","arg2_id":"22986","normalized":[]},{"id":"23008","type":"CID","arg1_id":"22972","arg2_id":"22997","normalized":[]},{"id":"23009","type":"CID","arg1_id":"22973","arg2_id":"22971","normalized":[]},{"id":"23010","type":"CID","arg1_id":"22973","arg2_id":"22982","normalized":[]},{"id":"23011","type":"CID","arg1_id":"22973","arg2_id":"22986","normalized":[]},{"id":"23012","type":"CID","arg1_id":"22973","arg2_id":"22997","normalized":[]},{"id":"23013","type":"CID","arg1_id":"22983","arg2_id":"22971","normalized":[]},{"id":"23014","type":"CID","arg1_id":"22983","arg2_id":"22982","normalized":[]},{"id":"23015","type":"CID","arg1_id":"22983","arg2_id":"22986","normalized":[]},{"id":"23016","type":"CID","arg1_id":"22983","arg2_id":"22997","normalized":[]},{"id":"23017","type":"CID","arg1_id":"22996","arg2_id":"22971","normalized":[]},{"id":"23018","type":"CID","arg1_id":"22996","arg2_id":"22982","normalized":[]},{"id":"23019","type":"CID","arg1_id":"22996","arg2_id":"22986","normalized":[]},{"id":"23020","type":"CID","arg1_id":"22996","arg2_id":"22997","normalized":[]},{"id":"23021","type":"CID","arg1_id":"22984","arg2_id":"22971","normalized":[]},{"id":"23022","type":"CID","arg1_id":"22984","arg2_id":"22982","normalized":[]},{"id":"23023","type":"CID","arg1_id":"22984","arg2_id":"22986","normalized":[]},{"id":"23024","type":"CID","arg1_id":"22984","arg2_id":"22997","normalized":[]},{"id":"23025","type":"CID","arg1_id":"22994","arg2_id":"22971","normalized":[]},{"id":"23026","type":"CID","arg1_id":"22994","arg2_id":"22982","normalized":[]},{"id":"23027","type":"CID","arg1_id":"22994","arg2_id":"22986","normalized":[]},{"id":"23028","type":"CID","arg1_id":"22994","arg2_id":"22997","normalized":[]},{"id":"23029","type":"CID","arg1_id":"22995","arg2_id":"22971","normalized":[]},{"id":"23030","type":"CID","arg1_id":"22995","arg2_id":"22982","normalized":[]},{"id":"23031","type":"CID","arg1_id":"22995","arg2_id":"22986","normalized":[]},{"id":"23032","type":"CID","arg1_id":"22995","arg2_id":"22997","normalized":[]}]}
{"id":"23033","document_id":"6308526","passages":[{"id":"23034","type":"title","text":["Naloxazone pretreatment modifies cardiorespiratory, temperature, and behavioral effects of morphine."],"offsets":[[0,100]]},{"id":"23035","type":"abstract","text":["Behavioral and cardiorespiratory responses to a lethal dose of morphine were evaluated in rats pretreated with saline or naloxazone, an antagonist of high-affinity mu 1 opioid receptors. Pretreatment with naloxazone significantly blocked morphine analgesia, catalepsy and hypothermia at a dose which completely eliminated high-affinity binding in brain membranes. Moreover, naloxazone significantly attenuated the morphine-induced hypotension and respiratory depression, whereas morphine-induced bradycardia was less affected. Results indicate that subpopulations of mu receptors may mediate selective behavioral and cardiorespiratory responses to morphine."],"offsets":[[101,758]]}],"entities":[{"id":"23036","type":"Chemical","text":["Naloxazone"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"C024224"}]},{"id":"23037","type":"Chemical","text":["morphine"],"offsets":[[91,99]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"23038","type":"Chemical","text":["morphine"],"offsets":[[164,172]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"23039","type":"Chemical","text":["naloxazone"],"offsets":[[222,232]],"normalized":[{"db_name":"MESH","db_id":"C024224"}]},{"id":"23040","type":"Chemical","text":["naloxazone"],"offsets":[[306,316]],"normalized":[{"db_name":"MESH","db_id":"C024224"}]},{"id":"23041","type":"Chemical","text":["morphine"],"offsets":[[339,347]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"23042","type":"Disease","text":["analgesia"],"offsets":[[348,357]],"normalized":[{"db_name":"MESH","db_id":"D000699"}]},{"id":"23043","type":"Disease","text":["catalepsy"],"offsets":[[359,368]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"23044","type":"Disease","text":["hypothermia"],"offsets":[[373,384]],"normalized":[{"db_name":"MESH","db_id":"D007035"}]},{"id":"23045","type":"Chemical","text":["naloxazone"],"offsets":[[475,485]],"normalized":[{"db_name":"MESH","db_id":"C024224"}]},{"id":"23046","type":"Chemical","text":["morphine"],"offsets":[[515,523]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"23047","type":"Disease","text":["hypotension"],"offsets":[[532,543]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"23048","type":"Disease","text":["respiratory depression"],"offsets":[[548,570]],"normalized":[{"db_name":"MESH","db_id":"D012131"}]},{"id":"23049","type":"Chemical","text":["morphine"],"offsets":[[580,588]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"23050","type":"Disease","text":["bradycardia"],"offsets":[[597,608]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"23051","type":"Chemical","text":["morphine"],"offsets":[[749,757]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]}],"events":[],"coreferences":[],"relations":[{"id":"23052","type":"CID","arg1_id":"23037","arg2_id":"23047","normalized":[]},{"id":"23053","type":"CID","arg1_id":"23038","arg2_id":"23047","normalized":[]},{"id":"23054","type":"CID","arg1_id":"23041","arg2_id":"23047","normalized":[]},{"id":"23055","type":"CID","arg1_id":"23046","arg2_id":"23047","normalized":[]},{"id":"23056","type":"CID","arg1_id":"23049","arg2_id":"23047","normalized":[]},{"id":"23057","type":"CID","arg1_id":"23051","arg2_id":"23047","normalized":[]},{"id":"23058","type":"CID","arg1_id":"23037","arg2_id":"23044","normalized":[]},{"id":"23059","type":"CID","arg1_id":"23038","arg2_id":"23044","normalized":[]},{"id":"23060","type":"CID","arg1_id":"23041","arg2_id":"23044","normalized":[]},{"id":"23061","type":"CID","arg1_id":"23046","arg2_id":"23044","normalized":[]},{"id":"23062","type":"CID","arg1_id":"23049","arg2_id":"23044","normalized":[]},{"id":"23063","type":"CID","arg1_id":"23051","arg2_id":"23044","normalized":[]},{"id":"23064","type":"CID","arg1_id":"23037","arg2_id":"23043","normalized":[]},{"id":"23065","type":"CID","arg1_id":"23038","arg2_id":"23043","normalized":[]},{"id":"23066","type":"CID","arg1_id":"23041","arg2_id":"23043","normalized":[]},{"id":"23067","type":"CID","arg1_id":"23046","arg2_id":"23043","normalized":[]},{"id":"23068","type":"CID","arg1_id":"23049","arg2_id":"23043","normalized":[]},{"id":"23069","type":"CID","arg1_id":"23051","arg2_id":"23043","normalized":[]},{"id":"23070","type":"CID","arg1_id":"23037","arg2_id":"23050","normalized":[]},{"id":"23071","type":"CID","arg1_id":"23038","arg2_id":"23050","normalized":[]},{"id":"23072","type":"CID","arg1_id":"23041","arg2_id":"23050","normalized":[]},{"id":"23073","type":"CID","arg1_id":"23046","arg2_id":"23050","normalized":[]},{"id":"23074","type":"CID","arg1_id":"23049","arg2_id":"23050","normalized":[]},{"id":"23075","type":"CID","arg1_id":"23051","arg2_id":"23050","normalized":[]}]}
{"id":"23076","document_id":"15897593","passages":[{"id":"23077","type":"title","text":["Dexrazoxane protects against myelosuppression from the DNA cleavage-enhancing drugs etoposide and daunorubicin but not doxorubicin."],"offsets":[[0,131]]},{"id":"23078","type":"abstract","text":["PURPOSE: The anthracyclines daunorubicin and doxorubicin and the epipodophyllotoxin etoposide are potent DNA cleavage-enhancing drugs that are widely used in clinical oncology; however, myelosuppression and cardiac toxicity limit their use. Dexrazoxane (ICRF-187) is recommended for protection against anthracycline-induced cardiotoxicity. EXPERIMENTAL DESIGN: Because of their widespread use, the hematologic toxicity following coadministration of dexrazoxane and these three structurally different DNA cleavage enhancers was investigated: Sensitivity of human and murine blood progenitor cells to etoposide, daunorubicin, and doxorubicin +\/- dexrazoxane was determined in granulocyte-macrophage colony forming assays. Likewise, in vivo, B6D2F1 mice were treated with etoposide, daunorubicin, and doxorubicin, with or without dexrazoxane over a wide range of doses: posttreatment, a full hematologic evaluation was done. RESULTS: Nontoxic doses of dexrazoxane reduced myelosuppression and weight loss from daunorubicin and etoposide in mice and antagonized their antiproliferative effects in the colony assay; however, dexrazoxane neither reduced myelosuppression, weight loss, nor the in vitro cytotoxicity from doxorubicin. CONCLUSION: Although our findings support the observation that dexrazoxane reduces neither hematologic activity nor antitumor activity from doxorubicin clinically, the potent antagonism of daunorubicin activity raises concern; a possible interference with anticancer efficacy certainly would call for renewed attention. Our data also suggest that significant etoposide dose escalation is perhaps possible by the use of dexrazoxane. Clinical trials in patients with brain metastases combining dexrazoxane and high doses of etoposide is ongoing with the aim of improving efficacy without aggravating hematologic toxicity. If successful, this represents an exciting mechanism for pharmacologic regulation of side effects from cytotoxic chemotherapy."],"offsets":[[132,2105]]}],"entities":[{"id":"23079","type":"Chemical","text":["Dexrazoxane"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D064730"}]},{"id":"23080","type":"Disease","text":["myelosuppression"],"offsets":[[29,45]],"normalized":[{"db_name":"MESH","db_id":"D001855"}]},{"id":"23081","type":"Chemical","text":["etoposide"],"offsets":[[84,93]],"normalized":[{"db_name":"MESH","db_id":"D005047"}]},{"id":"23082","type":"Chemical","text":["daunorubicin"],"offsets":[[98,110]],"normalized":[{"db_name":"MESH","db_id":"D003630"}]},{"id":"23083","type":"Chemical","text":["doxorubicin"],"offsets":[[119,130]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"23084","type":"Chemical","text":["anthracyclines"],"offsets":[[145,159]],"normalized":[{"db_name":"MESH","db_id":"D018943"}]},{"id":"23085","type":"Chemical","text":["daunorubicin"],"offsets":[[160,172]],"normalized":[{"db_name":"MESH","db_id":"D003630"}]},{"id":"23086","type":"Chemical","text":["doxorubicin"],"offsets":[[177,188]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"23087","type":"Chemical","text":["epipodophyllotoxin"],"offsets":[[197,215]],"normalized":[{"db_name":"MESH","db_id":"D011034"}]},{"id":"23088","type":"Chemical","text":["etoposide"],"offsets":[[216,225]],"normalized":[{"db_name":"MESH","db_id":"D005047"}]},{"id":"23089","type":"Disease","text":["myelosuppression"],"offsets":[[318,334]],"normalized":[{"db_name":"MESH","db_id":"D001855"}]},{"id":"23090","type":"Disease","text":["cardiac 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{"id":"23200","document_id":"6817363","passages":[{"id":"23201","type":"title","text":["Effects of the novel compound aniracetam (Ro 13-5057) upon impaired learning and memory in rodents."],"offsets":[[0,99]]},{"id":"23202","type":"abstract","text":["The effect of aniracetam (Ro 13-5057, 1-anisoyl-2-pyrrolidinone) was studied on various forms of experimentally impaired cognitive functions (learning and memory) in rodents and produced the following effects: (1) almost complete prevention of the incapacity to learn a discrete escape response in rats exposed to sublethal hypercapnia immediately before the acquisition session; (2) partial (rats) or complete (mice) prevention of the scopolamine-induced short-term amnesia for a passive avoidance task; (3) complete protection against amnesia for a passive avoidance task in rats submitted to electroconvulsive shock immediately after avoidance acquisition; (4) prevention of the long-term retention- or retrieval-deficit for a passive avoidance task induced in rats and mice by chloramphenicol or cycloheximide administered immediately after acquisition; (5) reversal, when administered as late as 1 h before the retention test, of the deficit in retention or retrieval of a passive avoidance task induced by cycloheximide injected 2 days previously; (6) prevention of the deficit in the retrieval of an active avoidance task induced in mice by subconvulsant electroshock or hypercapnia applied immediately before retrieval testing (24 h after acquisition). These improvements or normalizations of impaired cognitive functions were seen at oral aniracetam doses of 10-100 mg\/kg. Generally, the dose-response curves were bell-shaped. The mechanisms underlying the activity of aniracetam and its 'therapeutic window' are unknown. Piracetam, another pyrrolidinone derivative was used for comparison. It was active only in six of nine tests and had about one-tenth the potency of aniracetam. The results indicate that aniracetam improves cognitive functions which are impaired by different procedure and in different phases of the learning and memory process."],"offsets":[[100,1958]]}],"entities":[{"id":"23203","type":"Chemical","text":["aniracetam"],"offsets":[[30,40]],"normalized":[{"db_name":"MESH","db_id":"C036466"}]},{"id":"23204","type":"Chemical","text":["Ro 13-5057"],"offsets":[[42,52]],"normalized":[{"db_name":"MESH","db_id":"C036466"}]},{"id":"23205","type":"Disease","text":["impaired learning and memory"],"offsets":[[59,87]],"normalized":[{"db_name":"MESH","db_id":"D007859"},{"db_name":"MESH","db_id":"D008569"}]},{"id":"23206","type":"Disease","text":["impaired learning"],"offsets":[[59,76]],"normalized":[{"db_name":"MESH","db_id":"D007859"}]},{"id":"23207","type":"Disease","text":["impaired","memory"],"offsets":[[59,67],[81,87]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"23208","type":"Chemical","text":["aniracetam"],"offsets":[[114,124]],"normalized":[{"db_name":"MESH","db_id":"C036466"}]},{"id":"23209","type":"Chemical","text":["Ro 13-5057"],"offsets":[[126,136]],"normalized":[{"db_name":"MESH","db_id":"C036466"}]},{"id":"23210","type":"Chemical","text":["1-anisoyl-2-pyrrolidinone"],"offsets":[[138,163]],"normalized":[{"db_name":"MESH","db_id":"C036466"}]},{"id":"23211","type":"Disease","text":["impaired cognitive functions"],"offsets":[[212,240]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"23212","type":"Disease","text":["hypercapnia"],"offsets":[[424,435]],"normalized":[{"db_name":"MESH","db_id":"D006935"}]},{"id":"23213","type":"Chemical","text":["scopolamine"],"offsets":[[536,547]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"23214","type":"Disease","text":["amnesia"],"offsets":[[567,574]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"23215","type":"Disease","text":["amnesia"],"offsets":[[637,644]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"23216","type":"Chemical","text":["chloramphenicol"],"offsets":[[881,896]],"normalized":[{"db_name":"MESH","db_id":"D002701"}]},{"id":"23217","type":"Chemical","text":["cycloheximide"],"offsets":[[900,913]],"normalized":[{"db_name":"MESH","db_id":"D003513"}]},{"id":"23218","type":"Chemical","text":["cycloheximide"],"offsets":[[1112,1125]],"normalized":[{"db_name":"MESH","db_id":"D003513"}]},{"id":"23219","type":"Disease","text":["hypercapnia"],"offsets":[[1278,1289]],"normalized":[{"db_name":"MESH","db_id":"D006935"}]},{"id":"23220","type":"Disease","text":["impaired cognitive functions"],"offsets":[[1401,1429]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"23221","type":"Chemical","text":["aniracetam"],"offsets":[[1448,1458]],"normalized":[{"db_name":"MESH","db_id":"C036466"}]},{"id":"23222","type":"Chemical","text":["aniracetam"],"offsets":[[1578,1588]],"normalized":[{"db_name":"MESH","db_id":"C036466"}]},{"id":"23223","type":"Chemical","text":["Piracetam"],"offsets":[[1631,1640]],"normalized":[{"db_name":"MESH","db_id":"D010889"}]},{"id":"23224","type":"Chemical","text":["pyrrolidinone"],"offsets":[[1650,1663]],"normalized":[{"db_name":"MESH","db_id":"D011760"}]},{"id":"23225","type":"Chemical","text":["aniracetam"],"offsets":[[1779,1789]],"normalized":[{"db_name":"MESH","db_id":"C036466"}]},{"id":"23226","type":"Chemical","text":["aniracetam"],"offsets":[[1817,1827]],"normalized":[{"db_name":"MESH","db_id":"C036466"}]}],"events":[],"coreferences":[],"relations":[{"id":"23227","type":"CID","arg1_id":"23213","arg2_id":"23214","normalized":[]},{"id":"23228","type":"CID","arg1_id":"23213","arg2_id":"23215","normalized":[]},{"id":"23229","type":"CID","arg1_id":"23217","arg2_id":"23205","normalized":[]},{"id":"23230","type":"CID","arg1_id":"23217","arg2_id":"23207","normalized":[]},{"id":"23231","type":"CID","arg1_id":"23218","arg2_id":"23205","normalized":[]},{"id":"23232","type":"CID","arg1_id":"23218","arg2_id":"23207","normalized":[]},{"id":"23233","type":"CID","arg1_id":"23216","arg2_id":"23205","normalized":[]},{"id":"23234","type":"CID","arg1_id":"23216","arg2_id":"23207","normalized":[]}]}
{"id":"23235","document_id":"11900788","passages":[{"id":"23236","type":"title","text":["Nicotine potentiation of morphine-induced catalepsy in mice."],"offsets":[[0,60]]},{"id":"23237","type":"abstract","text":["In the present study, effects of nicotine on catalepsy induced by morphine in mice have been investigated. Morphine but not nicotine induced a dose-dependent catalepsy. The response of morphine was potentiated by nicotine. Intraperitoneal administration of atropine, naloxone, mecamylamine, and hexamethonium to mice reduced catalepsy induced by a combination of morphine with nicotine. Intracerebroventricular injection of atropine, hexamethonium, and naloxone also decreased catalepsy induced by morphine plus nicotine. Intraperitoneal administration of atropine, but not intraperitoneal or intracerebroventricular injection of hexamethonium, decreased the effect of a single dose of morphine. It was concluded that morphine catalepsy can be elicited by opioid and cholinergic receptors, and the potentiation of morphine induced by nicotine may also be mediated through cholinergic receptor mechanisms."],"offsets":[[61,965]]}],"entities":[{"id":"23238","type":"Chemical","text":["Nicotine"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"23239","type":"Chemical","text":["morphine"],"offsets":[[25,33]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"23240","type":"Disease","text":["catalepsy"],"offsets":[[42,51]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"23241","type":"Chemical","text":["nicotine"],"offsets":[[94,102]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"23242","type":"Disease","text":["catalepsy"],"offsets":[[106,115]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"23243","type":"Chemical","text":["morphine"],"offsets":[[127,135]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"23244","type":"Chemical","text":["Morphine"],"offsets":[[168,176]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"23245","type":"Chemical","text":["nicotine"],"offsets":[[185,193]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"23246","type":"Disease","text":["catalepsy"],"offsets":[[219,228]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"23247","type":"Chemical","text":["morphine"],"offsets":[[246,254]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"23248","type":"Chemical","text":["nicotine"],"offsets":[[274,282]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"23249","type":"Chemical","text":["atropine"],"offsets":[[318,326]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"23250","type":"Chemical","text":["naloxone"],"offsets":[[328,336]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"23251","type":"Chemical","text":["mecamylamine"],"offsets":[[338,350]],"normalized":[{"db_name":"MESH","db_id":"D008464"}]},{"id":"23252","type":"Chemical","text":["hexamethonium"],"offsets":[[356,369]],"normalized":[{"db_name":"MESH","db_id":"D018738"}]},{"id":"23253","type":"Disease","text":["catalepsy"],"offsets":[[386,395]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"23254","type":"Chemical","text":["morphine"],"offsets":[[424,432]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"23255","type":"Chemical","text":["nicotine"],"offsets":[[438,446]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"23256","type":"Chemical","text":["atropine"],"offsets":[[485,493]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"23257","type":"Chemical","text":["hexamethonium"],"offsets":[[495,508]],"normalized":[{"db_name":"MESH","db_id":"D018738"}]},{"id":"23258","type":"Chemical","text":["naloxone"],"offsets":[[514,522]],"normalized":[{"db_name":"MESH","db_id":"D009270"}]},{"id":"23259","type":"Disease","text":["catalepsy"],"offsets":[[538,547]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"23260","type":"Chemical","text":["morphine"],"offsets":[[559,567]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"23261","type":"Chemical","text":["nicotine"],"offsets":[[573,581]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]},{"id":"23262","type":"Chemical","text":["atropine"],"offsets":[[617,625]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"23263","type":"Chemical","text":["hexamethonium"],"offsets":[[691,704]],"normalized":[{"db_name":"MESH","db_id":"D018738"}]},{"id":"23264","type":"Chemical","text":["morphine"],"offsets":[[747,755]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"23265","type":"Chemical","text":["morphine"],"offsets":[[779,787]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"23266","type":"Disease","text":["catalepsy"],"offsets":[[788,797]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"23267","type":"Chemical","text":["morphine"],"offsets":[[875,883]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"23268","type":"Chemical","text":["nicotine"],"offsets":[[895,903]],"normalized":[{"db_name":"MESH","db_id":"D009538"}]}],"events":[],"coreferences":[],"relations":[{"id":"23269","type":"CID","arg1_id":"23239","arg2_id":"23240","normalized":[]},{"id":"23270","type":"CID","arg1_id":"23239","arg2_id":"23242","normalized":[]},{"id":"23271","type":"CID","arg1_id":"23239","arg2_id":"23246","normalized":[]},{"id":"23272","type":"CID","arg1_id":"23239","arg2_id":"23253","normalized":[]},{"id":"23273","type":"CID","arg1_id":"23239","arg2_id":"23259","normalized":[]},{"id":"23274","type":"CID","arg1_id":"23239","arg2_id":"23266","normalized":[]},{"id":"23275","type":"CID","arg1_id":"23243","arg2_id":"23240","normalized":[]},{"id":"23276","type":"CID","arg1_id":"23243","arg2_id":"23242","normalized":[]},{"id":"23277","type":"CID","arg1_id":"23243","arg2_id":"23246","normalized":[]},{"id":"23278","type":"CID","arg1_id":"23243","arg2_id":"23253","normalized":[]},{"id":"23279","type":"CID","arg1_id":"23243","arg2_id":"23259","normalized":[]},{"id":"23280","type":"CID","arg1_id":"23243","arg2_id":"23266","normalized":[]},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{"id":"23365","document_id":"11230490","passages":[{"id":"23366","type":"title","text":["Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer."],"offsets":[[0,237]]},{"id":"23367","type":"abstract","text":["PURPOSE: To determine whether Myocet (liposome-encapsulated doxorubicin; The Liposome Company, Elan Corporation, Princeton, NJ) in combination with cyclophosphamide significantly reduces doxorubicin cardiotoxicity while providing comparable antitumor efficacy in first-line treatment of metastatic breast cancer (MBC). PATIENTS AND METHODS: Two hundred ninety-seven patients with MBC and no prior chemotherapy for metastatic disease were randomized to receive either 60 mg\/m(2) of Myocet (M) or conventional doxorubicin (A), in combination with 600 mg\/m(2) of cyclophosphamide (C), every 3 weeks until disease progression or unacceptable toxicity. Cardiotoxicity was defined by reductions in left-ventricular ejection fraction, assessed by serial multigated radionuclide angiography scans, or congestive heart failure (CHF). Antitumor efficacy was assessed by objective tumor response rates (World Health Organization criteria), time to progression, and survival. RESULTS: Six percent of MC patients versus 21% (including five cases of CHF) of AC patients developed cardiotoxicity (P =.0002). Median cumulative doxorubicin dose at onset was more than 2,220 mg\/m(2) for MC versus 480 mg\/m(2) for AC (P =.0001, hazard ratio, 5.04). MC patients also experienced less grade 4 neutropenia. Antitumor efficacy of MC versus AC was comparable: objective response rates, 43% versus 43%; median time to progression, 5.1% versus 5.5 months; median time to treatment failure, 4.6 versus 4.4 months; and median survival, 19 versus 16 months. CONCLUSION: Myocet improves the therapeutic index of doxorubicin by significantly reducing cardiotoxicity and grade 4 neutropenia and provides comparable antitumor efficacy, when used in combination with cyclophosphamide as first-line therapy for MBC."],"offsets":[[238,2018]]}],"entities":[{"id":"23368","type":"Disease","text":["cardiotoxicity"],"offsets":[[8,22]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"23369","type":"Chemical","text":["doxorubicin"],"offsets":[[81,92]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"23370","type":"Chemical","text":["cyclophosphamide"],"offsets":[[97,113]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"23371","type":"Chemical","text":["doxorubicin"],"offsets":[[141,152]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"23372","type":"Chemical","text":["cyclophosphamide"],"offsets":[[157,173]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"23373","type":"Disease","text":["breast 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When BN 52021 (20 mg\/kg i.v.) was injected immediately after bupivacaine (2 mg\/kg), a partial reversion of the decrease of MBP and HR was observed, whereas the dose of 10 mg\/kg was ineffective. A partial recovery of bupivacaine-induced ECG alterations was observed after pretreatment of the rats with BN 52021. Since the administration of BN 52021, at all doses studied, did not alter MBP and HR at the doses used, the bulk of these results clearly demonstrate a protective action of BN 52021, a specific antagonist of PAF, against bupivacaine-induced cardiovascular toxicity. 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{"id":"23601","document_id":"2257294","passages":[{"id":"23602","type":"title","text":["Benzylacyclouridine reverses azidothymidine-induced marrow suppression without impairment of anti-human immunodeficiency virus activity."],"offsets":[[0,136]]},{"id":"23603","type":"abstract","text":["Increased extracellular concentrations of uridine (Urd) have been reported to reduce, in vitro, azidothymidine (AZT)-induced inhibition of human granulocyte-macrophage progenitor cells without impairment of its antihuman immunodeficiency virus (HIV) activity. Because of the clinical toxicities associated with chronic Urd administration, the ability of benzylacyclouridine (BAU) to effect, in vivo, AZT-induced anemia and leukopenia was assessed. This agent inhibits Urd catabolism and, in vivo, increases the plasma concentration of Urd in a dose-dependent manner, without Urd-related toxicity. In mice rendered anemic and leukopenic by the administration of AZT for 28 days in drinking water (1.5 mg\/mL), the continued administration of AZT plus daily BAU (300 mg\/kg, orally) partially reversed AZT-induced anemia and leukopenia (P less than .05), increased peripheral reticulocytes (to 4.9%, P less than .01), increased cellularity in the marrow, and improved megaloblastosis. When coadministered with AZT from the onset of drug administration, BAU reduced AZT-induced marrow toxicity. In vitro, at a concentration of 100 mumol\/L, BAU possesses minimal anti-HIV activity and has no effect on the ability of AZT to reverse the HIV-induced cytopathic effect in MT4 cells. The clinical and biochemical implications of these findings are discussed."],"offsets":[[137,1485]]}],"entities":[{"id":"23604","type":"Chemical","text":["Benzylacyclouridine"],"offsets":[[0,19]],"normalized":[{"db_name":"MESH","db_id":"C034753"}]},{"id":"23605","type":"Chemical","text":["azidothymidine"],"offsets":[[29,43]],"normalized":[{"db_name":"MESH","db_id":"D015215"}]},{"id":"23606","type":"Disease","text":["marrow 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{"id":"23719","document_id":"10840460","passages":[{"id":"23720","type":"title","text":["Cyclophosphamide-induced cystitis in freely-moving conscious rats: behavioral approach to a new model of visceral pain."],"offsets":[[0,119]]},{"id":"23721","type":"abstract","text":["PURPOSE: To develop a model of visceral pain in rats using a behavioral approach. Cyclophosphamide (CP), an antitumoral agent known to produce toxic effects on the bladder wall through its main toxic metabolite acrolein, was used to induce cystitis. MATERIALS AND METHODS: CP was administered at doses of 50, 100 and 200 mg.\/kg. i.p. to male rats, and their behavior observed and scored. The effects of morphine (0.5 to 4 mg.\/kg. i.v.) on CP-induced behavioral modifications were tested administered alone and after naloxone (1 mg.\/kg. s.c.). In addition, 90 minutes after CP injection, that is, at the time of administration of morphine, the bladder was removed in some rats for histological examination. Finally, to show that the bladder is essential for the CP-induced behavioral modifications, female rats also received CP at doses of 200 mg.\/kg. i.p. and of 20 mg. by the intravesical route, and acrolein at doses of 0.5 mg. by the intravesical route and of 5 mg.\/kg. i.v. RESULTS: CP dose-relatedly induced marked behavioral modifications in male rats: breathing rate decrease, closing of the eyes and occurrence of specific postures. Morphine dose-dependently reversed these behavioral disorders. A dose of 0.5 mg.\/kg. produced a reduction of almost 50% of the behavioral score induced by CP 200 mg.\/kg. This effect was completely prevented by pretreatment with naloxone. At the time of administration of morphine, histological modifications of the bladder wall, such as chorionic and muscle layer edema, were observed. In female rats, CP 200 mg.\/kg. i.p. produced the same marked behavioral modifications as those observed in male rats. Administered at the dose of 20 mg. intravesically, CP did not produce any behavioral effects, whereas acrolein at 0.5 mg. intravesically induced behavioral modifications identical to those under CP 200 mg.\/kg. i.p., with the same maximal levels. Conversely, acrolein 5 mg.\/kg. i.v. did not produce any behavioral effects at all. CONCLUSIONS: Overall, these results indicate that this experimental model of CP-induced cystitis may be an interesting new behavioral model of inflammatory visceral pain, allowing a better understanding of these painful syndromes and thus a better therapeutic approach to them."],"offsets":[[120,2371]]}],"entities":[{"id":"23722","type":"Chemical","text":["Cyclophosphamide"],"offsets":[[0,16]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"23723","type":"Disease","text":["cystitis"],"offsets":[[25,33]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"23724","type":"Disease","text":["visceral pain"],"offsets":[[105,118]],"normalized":[{"db_name":"MESH","db_id":"D059265"}]},{"id":"23725","type":"Disease","text":["visceral 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{"id":"23815","document_id":"8278214","passages":[{"id":"23816","type":"title","text":["Hyperalgesia and myoclonus in terminal cancer patients treated with continuous intravenous morphine."],"offsets":[[0,100]]},{"id":"23817","type":"abstract","text":["Eight cancer patients in the terminal stages of the disease treated with high doses of intravenous morphine developed hyperalgesia. All cases were retrospectively sampled from three different hospitals in Copenhagen. Five patients developed universal hyperalgesia and hyperesthesia which in 2 cases were accompanied by myoclonus. In 3 patients a pre-existing neuralgia increased to excruciating intensity and in 2 of these cases myoclonus occurred simultaneously. Although only few clinical descriptions of the relationship between hyperalgesia\/myoclonus and high doses of morphine are available, experimental support from animal studies indicates that morphine, or its metabolites, plays a causative role for the observed behavioural syndrome. The possible mechanisms are discussed and treatment proposals given suggesting the use of more efficacious opioids with less excitatory potency in these situations."],"offsets":[[101,1010]]}],"entities":[{"id":"23818","type":"Disease","text":["Hyperalgesia"],"offsets":[[0,12]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"23819","type":"Disease","text":["myoclonus"],"offsets":[[17,26]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"23820","type":"Disease","text":["cancer"],"offsets":[[39,45]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"23821","type":"Chemical","text":["morphine"],"offsets":[[91,99]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"23822","type":"Disease","text":["cancer"],"offsets":[[107,113]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"23823","type":"Chemical","text":["morphine"],"offsets":[[200,208]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"23824","type":"Disease","text":["hyperalgesia"],"offsets":[[219,231]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"23825","type":"Disease","text":["hyperalgesia"],"offsets":[[352,364]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"23826","type":"Disease","text":["hyperesthesia"],"offsets":[[369,382]],"normalized":[{"db_name":"MESH","db_id":"D006941"}]},{"id":"23827","type":"Disease","text":["myoclonus"],"offsets":[[420,429]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"23828","type":"Disease","text":["neuralgia"],"offsets":[[460,469]],"normalized":[{"db_name":"MESH","db_id":"D009437"}]},{"id":"23829","type":"Disease","text":["myoclonus"],"offsets":[[530,539]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"23830","type":"Disease","text":["hyperalgesia"],"offsets":[[633,645]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"23831","type":"Disease","text":["myoclonus"],"offsets":[[646,655]],"normalized":[{"db_name":"MESH","db_id":"D009207"}]},{"id":"23832","type":"Chemical","text":["morphine"],"offsets":[[674,682]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]},{"id":"23833","type":"Chemical","text":["morphine"],"offsets":[[754,762]],"normalized":[{"db_name":"MESH","db_id":"D009020"}]}],"events":[],"coreferences":[],"relations":[{"id":"23834","type":"CID","arg1_id":"23821","arg2_id":"23818","normalized":[]},{"id":"23835","type":"CID","arg1_id":"23821","arg2_id":"23824","normalized":[]},{"id":"23836","type":"CID","arg1_id":"23821","arg2_id":"23825","normalized":[]},{"id":"23837","type":"CID","arg1_id":"23821","arg2_id":"23830","normalized":[]},{"id":"23838","type":"CID","arg1_id":"23823","arg2_id":"23818","normalized":[]},{"id":"23839","type":"CID","arg1_id":"23823","arg2_id":"23824","normalized":[]},{"id":"23840","type":"CID","arg1_id":"23823","arg2_id":"23825","normalized":[]},{"id":"23841","type":"CID","arg1_id":"23823","arg2_id":"23830","normalized":[]},{"id":"23842","type":"CID","arg1_id":"23832","arg2_id":"23818","normalized":[]},{"id":"23843","type":"CID","arg1_id":"23832","arg2_id":"23824","normalized":[]},{"id":"23844","type":"CID","arg1_id":"23832","arg2_id":"23825","normalized":[]},{"id":"23845","type":"CID","arg1_id":"23832","arg2_id":"23830","normalized":[]},{"id":"23846","type":"CID","arg1_id":"23833","arg2_id":"23818","normalized":[]},{"id":"23847","type":"CID","arg1_id":"23833","arg2_id":"23824","normalized":[]},{"id":"23848","type":"CID","arg1_id":"23833","arg2_id":"23825","normalized":[]},{"id":"23849","type":"CID","arg1_id":"23833","arg2_id":"23830","normalized":[]},{"id":"23850","type":"CID","arg1_id":"23821","arg2_id":"23826","normalized":[]},{"id":"23851","type":"CID","arg1_id":"23823","arg2_id":"23826","normalized":[]},{"id":"23852","type":"CID","arg1_id":"23832","arg2_id":"23826","normalized":[]},{"id":"23853","type":"CID","arg1_id":"23833","arg2_id":"23826","normalized":[]},{"id":"23854","type":"CID","arg1_id":"23821","arg2_id":"23828","normalized":[]},{"id":"23855","type":"CID","arg1_id":"23823","arg2_id":"23828","normalized":[]},{"id":"23856","type":"CID","arg1_id":"23832","arg2_id":"23828","normalized":[]},{"id":"23857","type":"CID","arg1_id":"23833","arg2_id":"23828","normalized":[]},{"id":"23858","type":"CID","arg1_id":"23821","arg2_id":"23819","normalized":[]},{"id":"23859","type":"CID","arg1_id":"23821","arg2_id":"23827","normalized":[]},{"id":"23860","type":"CID","arg1_id":"23821","arg2_id":"23829","normalized":[]},{"id":"23861","type":"CID","arg1_id":"23821","arg2_id":"23831","normalized":[]},{"id":"23862","type":"CID","arg1_id":"23823","arg2_id":"23819","normalized":[]},{"id":"23863","type":"CID","arg1_id":"23823","arg2_id":"23827","normalized":[]},{"id":"23864","type":"CID","arg1_id":"23823","arg2_id":"23829","normalized":[]},{"id":"23865","type":"CID","arg1_id":"23823","arg2_id":"23831","normalized":[]},{"id":"23866","type":"CID","arg1_id":"23832","arg2_id":"23819","normalized":[]},{"id":"23867","type":"CID","arg1_id":"23832","arg2_id":"23827","normalized":[]},{"id":"23868","type":"CID","arg1_id":"23832","arg2_id":"23829","normalized":[]},{"id":"23869","type":"CID","arg1_id":"23832","arg2_id":"23831","normaliz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{"id":"23874","document_id":"3934126","passages":[{"id":"23875","type":"title","text":["A prospective study of adverse reactions associated with vancomycin therapy."],"offsets":[[0,76]]},{"id":"23876","type":"abstract","text":["A prospective evaluation of the efficacy and safety of vancomycin was conducted in 54 consecutive patients over a 16-month period. Vancomycin was curative in 95% of 43 patients with proven infection. Drugs were ceased in six patients because of adverse reactions; in three of these vancomycin was considered the likely cause. Reactions included thrombophlebitis (20 of 54 patients), rash (4 of 54), nephrotoxicity (4 of 50), proteinuria (1 of 50) and ototoxicity (1 of 11 patients tested by audiometry). Thrombophlebitis occurred only with infusion through peripheral cannulae; nephrotoxicity and ototoxicity were confined to patients receiving an aminoglycoside plus vancomycin. We conclude that vancomycin, administered appropriately, constitutes safe, effective therapy for infections caused by susceptible bacteria."],"offsets":[[77,896]]}],"entities":[{"id":"23877","type":"Chemical","text":["vancomycin"],"offsets":[[57,67]],"normalized":[{"db_name":"MESH","db_id":"D014640"}]},{"id":"23878","type":"Chemical","text":["vancomycin"],"offsets":[[132,142]],"normalized":[{"db_name":"MESH","db_id":"D014640"}]},{"id":"23879","type":"Chemical","text":["Vancomycin"],"offsets":[[208,218]],"normalized":[{"db_name":"MESH","db_id":"D014640"}]},{"id":"23880","type":"Disease","text":["infection"],"offsets":[[266,275]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"23881","type":"Chemical","text":["vancomycin"],"offsets":[[359,369]],"normalized":[{"db_name":"MESH","db_id":"D014640"}]},{"id":"23882","type":"Disease","text":["thrombophlebitis"],"offsets":[[422,438]],"normalized":[{"db_name":"MESH","db_id":"D013924"}]},{"id":"23883","type":"Disease","text":["rash"],"offsets":[[460,464]],"normalized":[{"db_name":"MESH","db_id":"D005076"}]},{"id":"23884","type":"Disease","text":["nephrotoxicity"],"offsets":[[476,490]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"23885","type":"Disease","text":["proteinuria"],"offsets":[[502,513]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"23886","type":"Disease","text":["ototoxicity"],"offsets":[[528,539]],"normalized":[{"db_name":"MESH","db_id":"D006311"}]},{"id":"23887","type":"Disease","text":["Thrombophlebitis"],"offsets":[[581,597]],"normalized":[{"db_name":"MESH","db_id":"D013924"}]},{"id":"23888","type":"Disease","text":["nephrotoxicity"],"offsets":[[655,669]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"23889","type":"Disease","text":["ototoxicity"],"offsets":[[674,685]],"normalized":[{"db_name":"MESH","db_id":"D006311"}]},{"id":"23890","type":"Chemical","text":["aminoglycoside"],"offsets":[[725,739]],"normalized":[{"db_name":"MESH","db_id":"D000617"}]},{"id":"23891","type":"Chemical","text":["vancomycin"],"offsets":[[745,755]],"normalized":[{"db_name":"MESH","db_id":"D014640"}]},{"id":"23892","type":"Chemical","text":["vancomycin"],"offsets":[[774,784]],"normalized":[{"db_name":"MESH","db_id":"D014640"}]},{"id":"23893","type":"Disease","text":["infections"],"offsets":[[854,864]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]}],"events":[],"coreferences":[],"relations":[{"id":"23894","type":"CID","arg1_id":"23877","arg2_id":"23882","normalized":[]},{"id":"23895","type":"CID","arg1_id":"23877","arg2_id":"23887","normalized":[]},{"id":"23896","type":"CID","arg1_id":"23878","arg2_id":"23882","normalized":[]},{"id":"23897","type":"CID","arg1_id":"23878","arg2_id":"23887","normalized":[]},{"id":"23898","type":"CID","arg1_id":"23879","arg2_id":"23882","normalized":[]},{"id":"23899","type":"CID","arg1_id":"23879","arg2_id":"23887","normalized":[]},{"id":"23900","type":"CID","arg1_id":"23881","arg2_id":"23882","normalized":[]},{"id":"23901","type":"CID","arg1_id":"23881","arg2_id":"23887","normalized":[]},{"id":"23902","type":"CID","arg1_id":"23891","arg2_id":"23882","normalized":[]},{"id":"23903","type":"CID","arg1_id":"23891","arg2_id":"23887","normalized":[]},{"id":"23904","type":"CID","arg1_id":"23892","arg2_id":"23882","normalized":[]},{"id":"23905","type":"CID","arg1_id":"23892","arg2_id":"23887","normalized":[]},{"id":"23906","type":"CID","arg1_id":"23877","arg2_id":"23883","normalized":[]},{"id":"23907","type":"CID","arg1_id":"23878","arg2_id":"23883","normalized":[]},{"id":"23908","type":"CID","arg1_id":"23879","arg2_id":"23883","normalized":[]},{"id":"23909","type":"CID","arg1_id":"23881","arg2_id":"23883","normalized":[]},{"id":"23910","type":"CID","arg1_id":"23891","arg2_id":"23883","normalized":[]},{"id":"23911","type":"CID","arg1_id":"23892","arg2_id":"23883","normalized":[]},{"id":"23912","type":"CID","arg1_id":"23877","arg2_id":"23885","normalized":[]},{"id":"23913","type":"CID","arg1_id":"23878","arg2_id":"23885","normalized":[]},{"id":"23914","type":"CID","arg1_id":"23879","arg2_id":"23885","normalized":[]},{"id":"23915","type":"CID","arg1_id":"23881","arg2_id":"23885","normalized":[]},{"id":"23916","type":"CID","arg1_id":"23891","arg2_id":"23885","normalized":[]},{"id":"23917","type":"CID","arg1_id":"23892","arg2_id":"23885","normalized":[]},{"id":"23918","type":"CID","arg1_id":"23877","arg2_id":"23886","normalized":[]},{"id":"23919","type":"CID","arg1_id":"23877","arg2_id":"23889","normalized":[]},{"id":"23920","type":"CID","arg1_id":"23878","arg2_id":"23886","normalized":[]},{"id":"23921","type":"CID","arg1_id":"23878","arg2_id":"23889","normalized":[]},{"id":"23922","type":"CID","arg1_id":"23879","arg2_id":"23886","normalized":[]},{"id":"23923","type":"CID","arg1_id":"23879","arg2_id":"23889","normalized":[]},{"id":"23924","type":"CID","arg1_id":"23881","arg2_id":"23886","normalized":[]},{"id":"23925","type":"CID","arg1_id":"23881","arg2_id":"23889","normalized":[]},{"id":"23926","type":"CID","arg1_id":"23891","arg2_id":"23886","normalized":[]},{"id":"23927","type":"CID","arg1_id":"23891","arg2_id":"23889","norm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{"id":"23930","document_id":"1687392","passages":[{"id":"23931","type":"title","text":["Blockade of both D-1 and D-2 dopamine receptors may induce catalepsy in mice."],"offsets":[[0,77]]},{"id":"23932","type":"abstract","text":["1. The catalepsy induced by dopamine antagonists has been tested and the possible dopamine subtypes involved in catalepsy was determined. 2. Dopamine antagonist fluphenazine, D-1 antagonist SCH 23390 or D-2 antagonist sulpiride induced catalepsy. The effect of fluphenazine and sulpiride was dose-dependent. Combination of SCH 23390 with sulpiride did not induce catalepsy potentiation. 3. D-1 agonist SKF 38393 or D-2 agonist quinpirole decreased the catalepsy induced by fluphenazine, SCH 23390 or sulpiride. 4. Combination of SKF 38393 with quinpirole did not cause potentiated inhibitory effect on catalepsy induced by dopamine antagonists. 5. The data may indicate that although D-2 receptor blockade is involved in catalepsy, the D-1 receptor may plan a role."],"offsets":[[78,843]]}],"entities":[{"id":"23933","type":"Chemical","text":["dopamine"],"offsets":[[29,37]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"23934","type":"Disease","text":["catalepsy"],"offsets":[[59,68]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"23935","type":"Disease","text":["catalepsy"],"offsets":[[85,94]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"23936","type":"Chemical","text":["dopamine"],"offsets":[[106,114]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"23937","type":"Chemical","text":["dopamine"],"offsets":[[160,168]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"23938","type":"Disease","text":["catalepsy"],"offsets":[[190,199]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"23939","type":"Chemical","text":["Dopamine"],"offsets":[[219,227]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"23940","type":"Chemical","text":["fluphenazine"],"offsets":[[239,251]],"normalized":[{"db_name":"MESH","db_id":"D005476"}]},{"id":"23941","type":"Chemical","text":["SCH 23390"],"offsets":[[268,277]],"normalized":[{"db_name":"MESH","db_id":"C534628"}]},{"id":"23942","type":"Chemical","text":["sulpiride"],"offsets":[[296,305]],"normalized":[{"db_name":"MESH","db_id":"D013469"}]},{"id":"23943","type":"Disease","text":["catalepsy"],"offsets":[[314,323]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"23944","type":"Chemical","text":["fluphenazine"],"offsets":[[339,351]],"normalized":[{"db_name":"MESH","db_id":"D005476"}]},{"id":"23945","type":"Chemical","text":["sulpiride"],"offsets":[[356,365]],"normalized":[{"db_name":"MESH","db_id":"D013469"}]},{"id":"23946","type":"Chemical","text":["SCH 23390"],"offsets":[[401,410]],"normalized":[{"db_name":"MESH","db_id":"C534628"}]},{"id":"23947","type":"Chemical","text":["sulpiride"],"offsets":[[416,425]],"normalized":[{"db_name":"MESH","db_id":"D013469"}]},{"id":"23948","type":"Disease","text":["catalepsy"],"offsets":[[441,450]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"23949","type":"Chemical","text":["SKF 38393"],"offsets":[[480,489]],"normalized":[{"db_name":"MESH","db_id":"D015647"}]},{"id":"23950","type":"Chemical","text":["quinpirole"],"offsets":[[505,515]],"normalized":[{"db_name":"MESH","db_id":"D019257"}]},{"id":"23951","type":"Disease","text":["catalepsy"],"offsets":[[530,539]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"23952","type":"Chemical","text":["fluphenazine"],"offsets":[[551,563]],"normalized":[{"db_name":"MESH","db_id":"D005476"}]},{"id":"23953","type":"Chemical","text":["SCH 23390"],"offsets":[[565,574]],"normalized":[{"db_name":"MESH","db_id":"C534628"}]},{"id":"23954","type":"Chemical","text":["sulpiride"],"offsets":[[578,587]],"normalized":[{"db_name":"MESH","db_id":"D013469"}]},{"id":"23955","type":"Chemical","text":["SKF 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{"id":"24040","document_id":"19719056","passages":[{"id":"24041","type":"title","text":["Dextran-etodolac conjugates: synthesis, in vitro and in vivo evaluation."],"offsets":[[0,72]]},{"id":"24042","type":"abstract","text":["Etodolac (E), is a non-narcotic analgesic and antiinflammatory drug. A biodegradable polymer dextran has been utilized as a carrier for synthesis of etodolac-dextran conjugates (ED) to improve its aqueous solubility and reduce gastrointestinal side effects. An activated moiety, i.e. N-acylimidazole derivative of etodolac (EAI), was condensed with the polysaccharide polymer dextran of different molecular weights (40000, 60000, 110000 and 200000). IR spectral data confirmed formation of ester bonding in the conjugates. Etodolac contents were evaluated by UV-spectrophotometric analysis. The molecular weights were determined by measuring viscosity using the Mark-Howink-Sakurada equation. In vitro hydrolysis of ED was done in aqueous buffers (pH 1.2, 7.4, 9) and in 80% (v\/v) human plasma (pH 7.4). At pH 9, a higher rate of etodolac release from ED was observed as compared to aqueous buffer of pH 7.4 and 80% human plasma (pH 7.4), following first-order kinetics. In vivo investigations were performed in animals. Acute analgesic and antiinflammatory activities were ascertained using acetic acid induced writhing model (mice) and carrageenan-induced rat paw edema model, respectively. In comparison to control, E and ED1-ED4 showed highly significant analgesic and antiinflammatory activities (p <0.001). Biological evaluation suggested that conjugates (ED1-ED4) retained comparable analgesic and antiinflammatory activities with remarkably reduced ulcerogenicity as compared to their parent drug--etodolac."],"offsets":[[73,1588]]}],"entities":[{"id":"24043","type":"Chemical","text":["Dextran"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D003911"}]},{"id":"24044","type":"Chemical","text":["etodolac"],"offsets":[[8,16]],"normalized":[{"db_name":"MESH","db_id":"D017308"}]},{"id":"24045","type":"Chemical","text":["Etodolac"],"offsets":[[73,81]],"normalized":[{"db_name":"MESH","db_id":"D017308"}]},{"id":"24046","type":"Chemical","text":["E"],"offsets":[[83,84]],"normalized":[{"db_name":"MESH","db_id":"D017308"}]},{"id":"24047","type":"Chemical","text":["dextran"],"offsets":[[166,173]],"normalized":[{"db_name":"MESH","db_id":"D003911"}]},{"id":"24048","type":"Chemical","text":["etodolac"],"offsets":[[222,230]],"normalized":[{"db_name":"MESH","db_id":"D017308"}]},{"id":"24049","type":"Chemical","text":["dextran"],"offsets":[[231,238]],"normalized":[{"db_name":"MESH","db_id":"D003911"}]},{"id":"24050","type":"Chemical","text":["N-acylimidazole"],"offsets":[[357,372]],"normalized":[]},{"id":"24051","type":"Chemical","text":["etodolac"],"offsets":[[387,395]],"normalized":[{"db_name":"MESH","db_id":"D017308"}]},{"id":"24052","type":"Chemical","text":["EAI"],"offsets":[[397,400]],"normalized":[]},{"id":"24053","type":"Chemical","text":["dextran"],"offsets":[[449,456]],"normalized":[{"db_name":"MESH","db_id":"D003911"}]},{"id":"24054","type":"Chemical","text":["Etodolac"],"offsets":[[596,604]],"normalized":[{"db_name":"MESH","db_id":"D017308"}]},{"id":"24055","type":"Chemical","text":["etodolac"],"offsets":[[903,911]],"normalized":[{"db_name":"MESH","db_id":"D017308"}]},{"id":"24056","type":"Chemical","text":["acetic acid"],"offsets":[[1165,1176]],"normalized":[{"db_name":"MESH","db_id":"D019342"}]},{"id":"24057","type":"Disease","text":["writhing"],"offsets":[[1185,1193]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"24058","type":"Chemical","text":["carrageenan"],"offsets":[[1211,1222]],"normalized":[{"db_name":"MESH","db_id":"D002351"}]},{"id":"24059","type":"Disease","text":["edema"],"offsets":[[1239,1244]],"normalized":[{"db_name":"MESH","db_id":"D004487"}]},{"id":"24060","type":"Chemical","text":["E"],"offsets":[[1292,1293]],"normalized":[{"db_name":"MESH","db_id":"D017308"}]},{"id":"24061","type":"Chemical","text":["etodolac"],"offsets":[[1579,1587]],"normalized":[{"db_name":"MESH","db_id":"D017308"}]}],"events":[],"coreferences":[],"relations":[{"id":"24062","type":"CID","arg1_id":"24058","arg2_id":"24059","normalized":[]},{"id":"24063","type":"CID","arg1_id":"24058","arg2_id":"24057","normalized":[]}]}
{"id":"24064","document_id":"15266362","passages":[{"id":"24065","type":"title","text":["Hypersensitivity myocarditis complicating hypertrophic cardiomyopathy heart."],"offsets":[[0,76]]},{"id":"24066","type":"abstract","text":["The present report describes a case of eosinophilic myocarditis complicating hypertrophic cardiomyopathy. The 47-year-old female patient, known to have hypertrophic cardiomyopathy, was admitted with biventricular failure and managed aggressively with dobutamine infusion and other drugs while being assessed for heart transplantation. On transthoracic echocardiogram, she had moderate left ventricular dysfunction with regional variability and moderate mitral regurgitation. The recipient's heart showed the features of apical hypertrophic cardiomyopathy and myocarditis with abundant eosinophils. Myocarditis is rare and eosinophilic myocarditis is rarer. It is likely that the hypersensitivity (eosinophilic) myocarditis was related to dobutamine infusion therapy. Eosinophilic myocarditis has been reported with an incidence of 2.4% to 7.2% in explanted hearts and may be related to multidrug therapy."],"offsets":[[77,981]]}],"entities":[{"id":"24067","type":"Disease","text":["Hypersensitivity"],"offsets":[[0,16]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"24068","type":"Disease","text":["myocarditis"],"offsets":[[17,28]],"normalized":[{"db_name":"MESH","db_id":"D009205"}]},{"id":"24069","type":"Disease","text":["hypertrophic cardiomyopathy"],"offsets":[[42,69]],"normalized":[{"db_name":"MESH","db_id":"D002312"}]},{"id":"24070","type":"Disease","text":["eosinophilic myocarditis"],"offsets":[[116,140]],"normalized":[{"db_name":"MESH","db_id":"D004802"},{"db_name":"MESH","db_id":"D009205"}]},{"id":"24071","type":"Disease","text":["eosinophilic"],"offsets":[[116,128]],"normalized":[{"db_name":"MESH","db_id":"D004802"}]},{"id":"24072","type":"Disease","text":["myocarditis"],"offsets":[[129,140]],"normalized":[{"db_name":"MESH","db_id":"D009205"}]},{"id":"24073","type":"Disease","text":["hypertrophic cardiomyopathy"],"offsets":[[154,181]],"normalized":[{"db_name":"MESH","db_id":"D002312"}]},{"id":"24074","type":"Disease","text":["hypertrophic cardiomyopathy"],"offsets":[[229,256]],"normalized":[{"db_name":"MESH","db_id":"D002312"}]},{"id":"24075","type":"Disease","text":["biventricular failure"],"offsets":[[276,297]],"normalized":[{"db_name":"MESH","db_id":"D018754"}]},{"id":"24076","type":"Chemical","text":["dobutamine"],"offsets":[[328,338]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"24077","type":"Disease","text":["left ventricular dysfunction"],"offsets":[[462,490]],"normalized":[{"db_name":"MESH","db_id":"D018487"}]},{"id":"24078","type":"Disease","text":["mitral regurgitation"],"offsets":[[530,550]],"normalized":[{"db_name":"MESH","db_id":"D008944"}]},{"id":"24079","type":"Disease","text":["hypertrophic cardiomyopathy"],"offsets":[[604,631]],"normalized":[{"db_name":"MESH","db_id":"D002312"}]},{"id":"24080","type":"Disease","text":["myocarditis"],"offsets":[[636,647]],"normalized":[{"db_name":"MESH","db_id":"D009205"}]},{"id":"24081","type":"Disease","text":["Myocarditis"],"offsets":[[675,686]],"normalized":[{"db_name":"MESH","db_id":"D009205"}]},{"id":"24082","type":"Disease","text":["eosinophilic myocarditis"],"offsets":[[699,723]],"normalized":[{"db_name":"MESH","db_id":"D004802"},{"db_name":"MESH","db_id":"D009205"}]},{"id":"24083","type":"Disease","text":["eosinophilic"],"offsets":[[699,711]],"normalized":[{"db_name":"MESH","db_id":"D004802"}]},{"id":"24084","type":"Disease","text":["myocarditis"],"offsets":[[712,723]],"normalized":[{"db_name":"MESH","db_id":"D009205"}]},{"id":"24085","type":"Disease","text":["hypersensitivity"],"offsets":[[756,772]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"24086","type":"Disease","text":["eosinophilic"],"offsets":[[774,786]],"normalized":[{"db_name":"MESH","db_id":"D004802"}]},{"id":"24087","type":"Disease","text":["myocarditis"],"offsets":[[788,799]],"normalized":[{"db_name":"MESH","db_id":"D009205"}]},{"id":"24088","type":"Chemical","text":["dobutamine"],"offsets":[[815,825]],"normalized":[{"db_name":"MESH","db_id":"D004280"}]},{"id":"24089","type":"Disease","text":["Eosinophilic myocarditis"],"offsets":[[844,868]],"normalized":[{"db_name":"MESH","db_id":"D004802"},{"db_name":"MESH","db_id":"D009205"}]},{"id":"24090","type":"Disease","text":["Eosinophilic"],"offsets":[[844,856]],"normalized":[{"db_name":"MESH","db_id":"D004802"}]},{"id":"24091","type":"Disease","text":["myocarditis"],"offsets":[[857,868]],"normalized":[{"db_name":"MESH","db_id":"D009205"}]}],"events":[],"coreferences":[],"relations":[{"id":"24092","type":"CID","arg1_id":"24076","arg2_id":"24070","normalized":[]},{"id":"24093","type":"CID","arg1_id":"24076","arg2_id":"24071","normalized":[]},{"id":"24094","type":"CID","arg1_id":"24076","arg2_id":"24082","normalized":[]},{"id":"24095","type":"CID","arg1_id":"24076","arg2_id":"24083","normalized":[]},{"id":"24096","type":"CID","arg1_id":"24076","arg2_id":"24086","normalized":[]},{"id":"24097","type":"CID","arg1_id":"24076","arg2_id":"24089","normalized":[]},{"id":"24098","type":"CID","arg1_id":"24076","arg2_id":"24090","normalized":[]},{"id":"24099","type":"CID","arg1_id":"24088","arg2_id":"24070","normalized":[]},{"id":"24100","type":"CID","arg1_id":"24088","arg2_id":"24071","normalized":[]},{"id":"24101","type":"CID","arg1_id":"24088","arg2_id":"24082","normalized":[]},{"id":"24102","type":"CID","arg1_id":"24088","arg2_id":"24083","normalized":[]},{"id":"24103","type":"CID","arg1_id":"24088","arg2_id":"24086","normalized":[]},{"id":"24104","type":"CID","arg1_id":"24088","arg2_id":"24089","normalized":[]},{"id":"24105","type":"CID","arg1_id":"24088","arg2_id":"24090","normalized":[]},{"id":"24106","type":"CID","arg1_id":"24076","arg2_id":"24067","normalized":[]},{"id":"24107","type":"CID","arg1_id":"24076","arg2_id":"24085","normalized":[]},{"id":"24108","type":"CID","arg1_id":"24088","arg2_id":"24067","normalized":[]},{"id":"24109","type":"CID","arg1_id":"24088","arg2_id":"24085","normalized":[]},{"id":"24110","type":"CID","arg1_id":"24076","arg2_id":"24068","normalized":[]},{"id":"24111","type":"CID","arg1_id":"24076","arg2_id":"24070","normalized":[]},{"id":"24112","type":"CID","arg1_id":"24076","arg2_id":"24072","normalized":[]},{"id":"24113","type":"CID","arg1_id":"24076","arg2_id":"24080","normalized":[]},{"id":"24114","type":"CID","arg1_id":"24076","arg2_id":"24081","normalized":[]},{"id":"24115","type":"CID","arg1_id":"24076","arg2_id":"24082","normalized":[]},{"id":"24116","type":"CID","arg1_id":"24076","arg2_id":"24084","normalized":[]},{"id":"24117","type":"CID","arg1_id":"24076","arg2_id":"24087","normalized":[]},{"id":"24118","type":"CID","arg1_id":"24076","arg2_id":"24089","normalized":[]},{"id":"24119","type":"CID","arg1_id":"24076","arg2_id":"24091","normalized":[]},{"id":"24120","type":"CID","arg1_id":"24088","arg2_id":"24068","normalized":[]},{"id":"24121","type":"CID","arg1_id":"24088","arg2_id":"24070","normalized":[]},{"id":"24122","type":"CID","arg1_id":"24088","arg2_id":"24072","normalized":[]},{"id":"24123","type":"CID","arg1_id":"24088","arg2_id":"24080","normalized":[]},{"id":"24124","type":"CID","arg1_id":"24088","arg2_id":"24081","normalized":[]},{"id":"24125","type":"CID","arg1_id":"24088","arg2_id":"24082","normalized":[]},{"id":"24126","type":"CID","arg1_id":"24088","arg2_id":"24084","normalized":[]},{"id":"24127","type":"CID","arg1_id":"24088","arg2_id":"24087","normalized":[]},{"id":"24128","type":"CID","arg1_id":"24088","arg2_id":"24089","normalized":[]},{"id":"24129","type":"CID","arg1_id":"24088","arg2_id":"24091","normalized":[]}]}
{"id":"24130","document_id":"14648024","passages":[{"id":"24131","type":"title","text":["All- trans-retinoic acid-induced erythema nodosum in patients with acute promyelocytic leukemia."],"offsets":[[0,96]]},{"id":"24132","type":"abstract","text":["Erythema nodosum associated with all- trans-retinoic acid (ATRA) for acute promyelocytic leukemia (APL) is very rare. We describe four patients with classic APL who developed erythema nodosum during ATRA therapy. Fever and subsequent multiple painful erythematous nodules over extremities developed on D11, D16, D17, and D19, respectively, after ATRA therapy. The skin biopsy taken from each patient was consistent with erythema nodosum. All patients received short course of steroids. Fever subsided rapidly and the skin lesions regressed completely. All patients achieved complete remission without withdrawal of ATRA. ATRA seemed to be the most possible etiology of erythema nodosum in our patients. Short-term use of steroid is very effective in ATRA-induced erythema nodosum."],"offsets":[[97,877]]}],"entities":[{"id":"24133","type":"Chemical","text":["All- trans-retinoic acid"],"offsets":[[0,24]],"normalized":[{"db_name":"MESH","db_id":"D014212"}]},{"id":"24134","type":"Disease","text":["erythema nodosum"],"offsets":[[33,49]],"normalized":[{"db_name":"MESH","db_id":"D004893"}]},{"id":"24135","type":"Disease","text":["acute promyelocytic leukemia"],"offsets":[[67,95]],"normalized":[{"db_name":"MESH","db_id":"D015473"}]},{"id":"24136","type":"Disease","text":["Erythema nodosum"],"offsets":[[97,113]],"normalized":[{"db_name":"MESH","db_id":"D004893"}]},{"id":"24137","type":"Chemical","text":["all- trans-retinoic acid"],"offsets":[[130,154]],"normalized":[{"db_name":"MESH","db_id":"D014212"}]},{"id":"24138","type":"Chemical","text":["ATRA"],"offsets":[[156,160]],"normalized":[{"db_name":"MESH","db_id":"D014212"}]},{"id":"24139","type":"Disease","text":["acute promyelocytic leukemia"],"offsets":[[166,194]],"normalized":[{"db_name":"MESH","db_id":"D015473"}]},{"id":"24140","type":"Disease","text":["APL"],"offsets":[[196,199]],"normalized":[{"db_name":"MESH","db_id":"D015473"}]},{"id":"24141","type":"Disease","text":["APL"],"offsets":[[254,257]],"normalized":[{"db_name":"MESH","db_id":"D015473"}]},{"id":"24142","type":"Disease","text":["erythema nodosum"],"offsets":[[272,288]],"normalized":[{"db_name":"MESH","db_id":"D004893"}]},{"id":"24143","type":"Chemical","text":["ATRA"],"offsets":[[296,300]],"normalized":[{"db_name":"MESH","db_id":"D014212"}]},{"id":"24144","type":"Disease","text":["Fever"],"offsets":[[310,315]],"normalized":[{"db_name":"MESH","db_id":"D005334"}]},{"id":"24145","type":"Disease","text":["painful"],"offsets":[[340,347]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"24146","type":"Disease","text":["erythematous nodules"],"offsets":[[348,368]],"normalized":[{"db_name":"MESH","db_id":"D004893"}]},{"id":"24147","type":"Chemical","text":["ATRA"],"offsets":[[443,447]],"normalized":[{"db_name":"MESH","db_id":"D014212"}]},{"id":"24148","type":"Disease","text":["erythema nodosum"],"offsets":[[517,533]],"normalized":[{"db_name":"MESH","db_id":"D004893"}]},{"id":"24149","type":"Chemical","text":["steroids"],"offsets":[[573,581]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"24150","type":"Disease","text":["Fever"],"offsets":[[583,588]],"normalized":[{"db_name":"MESH","db_id":"D005334"}]},{"id":"24151","type":"Chemical","text":["ATRA"],"offsets":[[712,716]],"normalized":[{"db_name":"MESH","db_id":"D014212"}]},{"id":"24152","type":"Chemical","text":["ATRA"],"offsets":[[718,722]],"normalized":[{"db_name":"MESH","db_id":"D014212"}]},{"id":"24153","type":"Disease","text":["erythema nodosum"],"offsets":[[766,782]],"normalized":[{"db_name":"MESH","db_id":"D004893"}]},{"id":"24154","type":"Chemical","text":["steroid"],"offsets":[[818,825]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"24155","type":"Chemical","text":["ATRA"],"offsets":[[847,851]],"normalized":[{"db_name":"MESH","db_id":"D014212"}]},{"id":"24156","type":"Disease","text":["erythema nodosum"],"offsets":[[860,876]],"normalized":[{"db_name":"MESH","db_id":"D004893"}]}],"events":[],"coreferences":[],"relations":[{"id":"24157","type":"CID","arg1_id":"24133","arg2_id":"24134","normalized":[]},{"id":"24158","type":"CID","arg1_id":"24133","arg2_id":"24136","normalized":[]},{"id":"24159","type":"CID","arg1_id":"24133","arg2_id":"24142","normalized":[]},{"id":"24160","type":"CID","arg1_id":"24133","arg2_id":"24146","normalized":[]},{"id":"24161","type":"CID","arg1_id":"24133","arg2_id":"24148","normalized":[]},{"id":"24162","type":"CID","arg1_id":"24133","arg2_id":"24153","normalized":[]},{"id":"24163","type":"CID","arg1_id":"24133","arg2_id":"24156","normalized":[]},{"id":"24164","type":"CID","arg1_id":"24137","arg2_id":"24134","normalized":[]},{"id":"24165","type":"CID","arg1_id":"24137","arg2_id":"24136","normalized":[]},{"id":"24166","type":"CID","arg1_id":"24137","arg2_id":"24142","normalized":[]},{"id":"24167","type":"CID","arg1_id":"24137","arg2_id":"24146","normalized":[]},{"id":"24168","type":"CID","arg1_id":"24137","arg2_id":"24148","normalized":[]},{"id":"24169","type":"CID","arg1_id":"24137","arg2_id":"24153","normalized":[]},{"id":"24170","type":"CID","arg1_id":"24137","arg2_id":"24156","normalized":[]},{"id":"24171","type":"CID","arg1_id":"24138","arg2_id":"24134","normalized":[]},{"id":"24172","type":"CID","arg1_id":"24138","arg2_id":"24136","normalized":[]},{"id":"24173","type":"CID","arg1_id":"24138","arg2_id":"24142","normalized":[]},{"id":"24174","type":"CID","arg1_id":"24138","arg2_id":"24146","normalized":[]},{"id":"24175","type":"CID","arg1_id":"24138","arg2_id":"24148","normalized":[]},{"id":"24176","type":"CID","arg1_id":"24138","arg2_id":"24153","normalized":[]},{"id":"24177","type":"CID","arg1_id":"24138","arg2_id":"24156","normalized":[]},{"id":"24178","type":"CID","arg1_id":"24143","arg2_id":"24134","normalized":[]},{"id":"24179","type":"CID","arg1_id":"24143","arg2_id":"24136","normalized":[]},{"id":"24180","type":"CID","arg1_id":"24143","arg2_id":"24142","normalized":[]},{"id":"24181","type":"CID","arg1_id":"24143","arg2_id":"24146","normalized":[]},{"id":"24182","type":"CID","arg1_id":"24143","arg2_id":"24148","normalized":[]},{"id":"24183","type":"CID","arg1_id":"24143","arg2_id":"24153","normalized":[]},{"id":"24184","type":"CID","arg1_id":"24143","arg2_id":"24156","normalized":[]},{"id":"24185","type":"CID","arg1_id":"24147","arg2_id":"24134","normalized":[]},{"id":"24186","type":"CID","arg1_id":"24147","arg2_id":"24136","normalized":[]},{"id":"24187","type":"CID","arg1_id":"24147","arg2_id":"24142","normalized":[]},{"id":"24188","type":"CID","arg1_id":"24147","arg2_id":"24146","normalized":[]},{"id":"24189","type":"CID","arg1_id":"24147","arg2_id":"24148","normalized":[]},{"id":"24190","type":"CID","arg1_id":"24147","arg2_id":"24153","normalized":[]},{"id":"24191","type":"CID","arg1_id":"24147","arg2_id":"24156","normalized":[]},{"id":"24192","type":"CID","arg1_id":"24151","arg2_id":"24134","normalized":[]},{"id":"24193","type":"CID","arg1_id":"24151","arg2_id":"24136","normalized":[]},{"id":"24194","type":"CID","arg1_id":"24151","arg2_id":"24142","normalized":[]},{"id":"24195","type":"CID","arg1_id":"24151","arg2_id":"24146","normalized":[]},{"id":"24196","type":"CID","arg1_id":"24151","arg2_id":"24148","normalized":[]},{"id":"24197","type":"CID","arg1_id":"24151","arg2_id":"24153","normalized":[]},{"id":"24198","type":"CID","arg1_id":"24151","arg2_id":"24156","normalized":[]},{"id":"24199","type":"CID","arg1_id":"24152","arg2_id":"24134","normalized":[]},{"id":"24200","type":"CID","arg1_id":"24152","arg2_id":"24136","normalized":[]},{"id":"24201","type":"CID","arg1_id":"24152","arg2_id":"24142","normalized":[]},{"id":"24202","type":"CID","arg1_id":"24152","arg2_id":"24146","normalized":[]},{"id":"24203","type":"CID","arg1_id":"24152","arg2_id":"24148","normalized":[]},{"id":"24204","type":"CID","arg1_id":"24152","arg2_id":"24153","normalized":[]},{"id":"24205","type":"CID","arg1_id":"24152","arg2_id":"24156","normalized":[]},{"id":"24206","type":"CID","arg1_id":"24155","arg2_id":"24134","normalized":[]},{"id":"24207","type":"CID","arg1_id":"24155","arg2_id":"24136","normalized":[]},{"id":"24208","type":"CID","arg1_id":"24155","arg2_id":"24142","normalized":[]},{"id":"24209","type":"CID","arg1_id":"24155","arg2_id":"24146","normalized":[]},{"id":"24210","type":"CID","arg1_id":"24155","arg2_id":"24148","normalized":[]},{"id":"24211","type":"CID","arg1_id":"24155","arg2_id":"24153","normalized":[]},{"id":"24212","type":"CID","arg1_id":"24155","arg2_id":"24156","normalized":[]},{"id":"24213","type":"CID","arg1_id":"24133","arg2_id":"24144","normalized":[]},{"id":"24214","type":"CID","arg1_id":"24133","arg2_id":"24150","normalized":[]},{"id":"24215","type":"CID","arg1_id":"24137","arg2_id":"24144","normalized":[]},{"id":"24216","type":"CID","arg1_id":"24137","arg2_id":"24150","normalized":[]},{"id":"24217","type":"CID","arg1_id":"24138","arg2_id":"24144","normali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{"id":"24229","document_id":"11827497","passages":[{"id":"24230","type":"title","text":["Delayed-onset heparin-induced thrombocytopenia."],"offsets":[[0,47]]},{"id":"24231","type":"abstract","text":["BACKGROUND: Heparin-induced thrombocytopenia presents 5 to 12 days after heparin exposure, with or without arterial or venous thromboemboli. Delayed recognition and treatment of heparin-induced thrombocytopenia contribute to poor patient outcomes. OBJECTIVE: To describe and increase awareness of a clinical scenario in which the onset or manifestations of heparin-induced thrombocytopenia are delayed. DESIGN: Retrospective case series. SETTING: Three large urban hospitals (with active cardiovascular surgery programs). PATIENTS: 14 patients seen over a 3-year period in whom heparin-induced thrombocytopenia became apparent on delayed presentation with thromboembolic complications. MEASUREMENTS: Platelet counts, onset of objectively determined thromboembolism, results of heparin-induced platelet factor 4 antibody tests, and outcomes. RESULTS: Patients went home after hospitalizations that had included heparin exposure--in most cases, with no thrombocytopenia recognized--only to return to the hospital (median, day 14) with thromboembolic complications. Thromboemboli were venous (12 patients, 7 with pulmonary emboli) or arterial (4 patients) or both. Platelet counts were mildly decreased in all but 2 patients on second presentation. On readmission, 11 patients received therapeutic heparin, which worsened the patients' clinical condition and, in all 11 cases, decreased the platelet count (mean at readmission, 143 x 10(9) cells\/L; mean nadir after heparin re-exposure, 39 x 10(9) cells\/L). Results of serologic tests for heparin-induced antibodies were positive in all patients. Subsequent treatments included alternative anticoagulants (11 patients), thrombolytic drugs (3 patients), inferior vena cava filters (3 patients) and, eventually, warfarin (11 patients). Three patients died. CONCLUSIONS: Delayed-onset heparin-induced thrombocytopenia is increasingly being recognized. To avoid disastrous outcomes, physicians must consider heparin-induced thrombocytopenia whenever a recently hospitalized patient returns with thromboembolism; therapy with alternative anticoagulants, not heparin, should be initiated."],"offsets":[[48,2177]]}],"entities":[{"id":"24232","type":"Chemical","text":["heparin"],"offsets":[[14,21]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"24233","type":"Disease","text":["thrombocytopenia"],"offsets":[[30,46]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"24234","type":"Chemical","text":["Heparin"],"offsets":[[60,67]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"24235","type":"Disease","text":["thrombocytopenia"],"offsets":[[76,92]],"normalized":[{"db_name":"MESH","db_id":"D013921"}]},{"id":"24236","type":"Chemical","text":["heparin"],"offsets":[[121,128]],"normalized":[{"db_name":"MESH","db_id":"D006493"}]},{"id":"24237","type":"Disease","text":["arterial or venous 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{"id":"24446","document_id":"8841157","passages":[{"id":"24447","type":"title","text":["Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: a comparative study of the efficacy and safety against amlodipine."],"offsets":[[0,154]]},{"id":"24448","type":"abstract","text":["OBJECTIVE: To compare the antihypertensive efficacy of a new angiotensin II antagonist, valsartan, with a reference therapy, amlodipine. METHODS: One hundred sixty-eight adult outpatients with mild to moderate hypertension were randomly allocated in double-blind fashion and equal number to receive 80 mg valsartan or 5 mg amlodipine for 12 weeks. After 8 weeks of therapy, in patients whose blood pressure remained uncontrolled, 5 mg amlodipine was added to the initial therapy. Patients were assessed at 4, 8, and 12 weeks. The primary efficacy variable was change from baseline in mean sitting diastolic blood pressure at 8 weeks. Secondary variables included change in sitting systolic blood pressure and responder rates. RESULTS: Both valsartan and amlodipine were effective at lowering blood pressure at 4, 8, and 12 weeks. Similar decreases were observed in both groups, with no statistically significant differences between the groups for any variable analyzed. For the primary variable the difference was 0.5 mm Hg in favor of valsartan (p = 0.68; 95% confidence interval, -2.7 to 1.7). Responder rates at 8 weeks were 66.7% for valsartan and 60.2% for amlodipine (p = 0.39). Both treatments were well tolerated. The incidence of drug-related dependent edema was somewhat higher in the amlodipine group, particularly at a dose of 10 mg per day (2.4% for 80 mg valsartan; 3.6% for 5 mg amlodipine; 0% for valsartan plus 5 mg amlodipine; 14.3% for 10 mg amlodipine). CONCLUSIONS: The data show that valsartan is at least as effective as amlodipine in the treatment of mild to moderate hypertension. The results also show valsartan to be well tolerated and suggest that it is not associated with side effects characteristic of this comparator class, dihydropyridine calcium antagonists."],"offsets":[[155,1947]]}],"entities":[{"id":"24449","type":"Chemical","text":["Valsartan"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"C081489"}]},{"id":"24450","type":"Chemical","text":["angiotensin II"],"offsets":[[17,31]],"normalized":[{"db_name":"MESH","db_id":"D000804"}]},{"id":"24451","type":"Disease","text":["hypertension"],"offsets":[[74,86]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"24452","type":"Chemical","text":["amlodipine"],"offsets":[[143,153]],"normalized":[{"db_name":"MESH","db_id":"D017311"}]},{"id":"24453","type":"Chemical","text":["angiotensin 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{"id":"24499","document_id":"8045270","passages":[{"id":"24500","type":"title","text":["KF17837: a novel selective adenosine A2A receptor antagonist with anticataleptic activity."],"offsets":[[0,90]]},{"id":"24501","type":"abstract","text":["KF17837 is a novel selective adenosine A2A receptor antagonist. Oral administration of KF17837 (2.5, 10.0 and 30.0 mg\/kg) significantly ameliorated the cataleptic responses induced by intracerebroventricular administration of an adenosine A2A receptor agonist, CGS 21680 (10 micrograms), in a dose-dependent manner. KF17837 also reduced the catalepsy induced by haloperidol (1 mg\/kg i.p.) and by reserpine (5 mg\/kg i.p.). These anticataleptic effects were exhibited dose dependently at doses from 0.625 and 2.5 mg\/kg p.o., respectively. Moreover, KF17837 (0.625 mg\/kg p.o.) potentiated the anticataleptic effects of a subthreshold dose of L-3,4-dihydroxyphenylalanine (L-DOPA; 25 mg\/kg i.p.) plus benserazide (6.25 mg\/kg i.p.). These results suggested that KF17837 is a centrally active adenosine A2A receptor antagonist and that the dopaminergic function of the nigrostriatal pathway is potentiated by adenosine A2A receptor antagonists. Furthermore, KF17837 may be a useful drug in the treatment of parkinsonism."],"offsets":[[91,1105]]}],"entities":[{"id":"24502","type":"Chemical","text":["KF17837"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"C081198"}]},{"id":"24503","type":"Chemical","text":["adenosine"],"offsets":[[27,36]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"24504","type":"Chemical","text":["KF17837"],"offsets":[[91,98]],"normalized":[{"db_name":"MESH","db_id":"C081198"}]},{"id":"24505","type":"Chemical","text":["adenosine"],"offsets":[[120,129]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"24506","type":"Chemical","text":["KF17837"],"offsets":[[178,185]],"normalized":[{"db_name":"MESH","db_id":"C081198"}]},{"id":"24507","type":"Disease","text":["cataleptic"],"offsets":[[243,253]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"24508","type":"Chemical","text":["adenosine"],"offsets":[[320,329]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"24509","type":"Chemical","text":["CGS 21680"],"offsets":[[352,361]],"normalized":[{"db_name":"MESH","db_id":"C061282"}]},{"id":"24510","type":"Chemical","text":["KF17837"],"offsets":[[407,414]],"normalized":[{"db_name":"MESH","db_id":"C081198"}]},{"id":"24511","type":"Disease","text":["catalepsy"],"offsets":[[432,441]],"normalized":[{"db_name":"MESH","db_id":"D002375"}]},{"id":"24512","type":"Chemical","text":["haloperidol"],"offsets":[[453,464]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"24513","type":"Chemical","text":["reserpine"],"offsets":[[487,496]],"normalized":[{"db_name":"MESH","db_id":"D012110"}]},{"id":"24514","type":"Chemical","text":["KF17837"],"offsets":[[638,645]],"normalized":[{"db_name":"MESH","db_id":"C081198"}]},{"id":"24515","type":"Chemical","text":["L-3,4-dihydroxyphenylalanine"],"offsets":[[730,758]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"24516","type":"Chemical","text":["L-DOPA"],"offsets":[[760,766]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"24517","type":"Chemical","text":["benserazide"],"offsets":[[788,799]],"normalized":[{"db_name":"MESH","db_id":"D001545"}]},{"id":"24518","type":"Chemical","text":["KF17837"],"offsets":[[848,855]],"normalized":[{"db_name":"MESH","db_id":"C081198"}]},{"id":"24519","type":"Chemical","text":["adenosine"],"offsets":[[878,887]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"24520","type":"Chemical","text":["adenosine"],"offsets":[[994,1003]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"24521","type":"Chemical","text":["KF17837"],"offsets":[[1043,1050]],"normalized":[{"db_name":"MESH","db_id":"C081198"}]},{"id":"24522","type":"Disease","text":["parkinsonism"],"offsets":[[1092,1104]],"normalized":[{"db_name":"MESH","db_id":"D010302"}]}],"events":[],"coreferences":[],"relations":[{"id":"24523","type":"CID","arg1_id":"24513","arg2_id":"24507","normalized":[]},{"id":"24524","type":"CID","arg1_id":"24513","arg2_id":"24511","normalized":[]},{"id":"24525","type":"CID","arg1_id":"24509","arg2_id":"24507","normalized":[]},{"id":"24526","type":"CID","arg1_id":"24509","arg2_id":"24511","normalized":[]},{"id":"24527","type":"CID","arg1_id":"24512","arg2_id":"24507","normalized":[]},{"id":"24528","type":"CID","arg1_id":"24512","arg2_id":"24511","normalized":[]}]}
{"id":"24529","document_id":"2576810","passages":[{"id":"24530","type":"title","text":["Some central effects of repeated treatment with fluvoxamine."],"offsets":[[0,60]]},{"id":"24531","type":"abstract","text":["We investigated the effect of repeated treatment with fluvoxamine, a selective serotonin uptake inhibitor, on behavioral effects of dopaminomimetics and methoxamine and on the animal behavior in the \"behavioral despair\" test. A repeated treatment with fluvoxamine (twice daily for 14 days) potentiated in mice and in rats (weaker) the amphetamine-induced hyperactivity. The hyperactivity induced by nomifensine in mice remained unaffected by fluvoxamine. The stimulation of locomotor activity by intracerebroventricularly administered methoxamine was not affected by repeated treatment with fluvoxamine. Given three times fluvoxamine had no effect on the immobilization time in the \"behavioral despair\" test in rats. The results indicate that fluvoxamine given repeatedly acts differently than citalopram, another selective serotonin uptake inhibitor, and differs also from other antidepressant drugs."],"offsets":[[61,962]]}],"entities":[{"id":"24532","type":"Chemical","text":["fluvoxamine"],"offsets":[[48,59]],"normalized":[{"db_name":"MESH","db_id":"D016666"}]},{"id":"24533","type":"Chemical","text":["fluvoxamine"],"offsets":[[115,126]],"normalized":[{"db_name":"MESH","db_id":"D016666"}]},{"id":"24534","type":"Chemical","text":["serotonin"],"offsets":[[140,149]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]},{"id":"24535","type":"Chemical","text":["methoxamine"],"offsets":[[214,225]],"normalized":[{"db_name":"MESH","db_id":"D008729"}]},{"id":"24536","type":"Chemical","text":["fluvoxamine"],"offsets":[[313,324]],"normalized":[{"db_name":"MESH","db_id":"D016666"}]},{"id":"24537","type":"Chemical","text":["amphetamine"],"offsets":[[396,407]],"normalized":[{"db_name":"MESH","db_id":"D000661"}]},{"id":"24538","type":"Disease","text":["hyperactivity"],"offsets":[[416,429]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"24539","type":"Disease","text":["hyperactivity"],"offsets":[[435,448]],"normalized":[{"db_name":"MESH","db_id":"D006948"}]},{"id":"24540","type":"Chemical","text":["nomifensine"],"offsets":[[460,471]],"normalized":[{"db_name":"MESH","db_id":"D009627"}]},{"id":"24541","type":"Chemical","text":["fluvoxamine"],"offsets":[[503,514]],"normalized":[{"db_name":"MESH","db_id":"D016666"}]},{"id":"24542","type":"Chemical","text":["methoxamine"],"offsets":[[596,607]],"normalized":[{"db_name":"MESH","db_id":"D008729"}]},{"id":"24543","type":"Chemical","text":["fluvoxamine"],"offsets":[[652,663]],"normalized":[{"db_name":"MESH","db_id":"D016666"}]},{"id":"24544","type":"Chemical","text":["fluvoxamine"],"offsets":[[683,694]],"normalized":[{"db_name":"MESH","db_id":"D016666"}]},{"id":"24545","type":"Chemical","text":["fluvoxamine"],"offsets":[[804,815]],"normalized":[{"db_name":"MESH","db_id":"D016666"}]},{"id":"24546","type":"Chemical","text":["citalopram"],"offsets":[[855,865]],"normalized":[{"db_name":"MESH","db_id":"D015283"}]},{"id":"24547","type":"Chemical","text":["serotonin"],"offsets":[[885,894]],"normalized":[{"db_name":"MESH","db_id":"D012701"}]}],"events":[],"coreferences":[],"relations":[{"id":"24548","type":"CID","arg1_id":"24532","arg2_id":"24538","normalized":[]},{"id":"24549","type":"CID","arg1_id":"24532","arg2_id":"24539","normalized":[]},{"id":"24550","type":"CID","arg1_id":"24533","arg2_id":"24538","normalized":[]},{"id":"24551","type":"CID","arg1_id":"24533","arg2_id":"24539","normalized":[]},{"id":"24552","type":"CID","arg1_id":"24536","arg2_id":"24538","normalized":[]},{"id":"24553","type":"CID","arg1_id":"24536","arg2_id":"24539","normalized":[]},{"id":"24554","type":"CID","arg1_id":"24541","arg2_id":"24538","normalized":[]},{"id":"24555","type":"CID","arg1_id":"24541","arg2_id":"24539","normalized":[]},{"id":"24556","type":"CID","arg1_id":"24543","arg2_id":"24538","normalized":[]},{"id":"24557","type":"CID","arg1_id":"24543","arg2_id":"24539","normalized":[]},{"id":"24558","type":"CID","arg1_id":"24544","arg2_id":"24538","normalized":[]},{"id":"24559","type":"CID","arg1_id":"24544","arg2_id":"24539","normalized":[]},{"id":"24560","type":"CID","arg1_id":"24545","arg2_id":"24538","normalized":[]},{"id":"24561","type":"CID","arg1_id":"24545","arg2_id":"24539","normalized":[]},{"id":"24562","type":"CID","arg1_id":"24535","arg2_id":"24538","normalized":[]},{"id":"24563","type":"CID","arg1_id":"24535","arg2_id":"24539","normalized":[]},{"id":"24564","type":"CID","arg1_id":"24542","arg2_id":"24538","normalized":[]},{"id":"24565","type":"CID","arg1_id":"24542","arg2_id":"24539","normalized":[]},{"id":"24566","type":"CID","arg1_id":"24540","arg2_id":"24538","normalized":[]},{"id":"24567","type":"CID","arg1_id":"24540","arg2_id":"24539","normalized":[]},{"id":"24568","type":"CID","arg1_id":"24537","arg2_id":"24538","normalized":[]},{"id":"24569","type":"CID","arg1_id":"24537","arg2_id":"24539","normalized":[]}]}
{"id":"24570","document_id":"20635749","passages":[{"id":"24571","type":"title","text":["Severe congestive heart failure patient on amiodarone presenting with myxedemic coma: a case report."],"offsets":[[0,100]]},{"id":"24572","type":"abstract","text":["This is a case report of myxedema coma secondary to amiodarone-induced hypothyroidism in a patient with severe congestive heart failure (CHF). To our knowledge and after reviewing the literature there is one case report of myxedema coma during long term amiodarone therapy. Myxedema coma is a life threatening condition that carries a mortality reaching as high as 20% with treatment. The condition is treated with intravenous thyroxine (T4) or intravenous tri-iodo-thyronine (T3). Patients with CHF on amiodarone may suffer serious morbidity and mortality from hypothyroidism, and thus may deserve closer follow up for thyroid stimulating hormone (TSH) levels. This case report carries an important clinical application given the frequent usage of amiodarone among CHF patients. The myriad clinical presentation of myxedema coma and its serious morbidity and mortality stresses the need to suspect this clinical syndrome among CHF patients presenting with hypotension, weakness or other unexplained symptoms."],"offsets":[[101,1110]]}],"entities":[{"id":"24573","type":"Disease","text":["congestive heart failure"],"offsets":[[7,31]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"24574","type":"Chemical","text":["amiodarone"],"offsets":[[43,53]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"24575","type":"Disease","text":["myxedemic coma"],"offsets":[[70,84]],"normalized":[{"db_name":"MESH","db_id":"D009230"},{"db_name":"MESH","db_id":"D003128"}]},{"id":"24576","type":"Disease","text":["myxedemic"],"offsets":[[70,79]],"normalized":[{"db_name":"MESH","db_id":"D009230"}]},{"id":"24577","type":"Disease","text":["coma"],"offsets":[[80,84]],"normalized":[{"db_name":"MESH","db_id":"D003128"}]},{"id":"24578","type":"Disease","text":["myxedema 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{"id":"24717","document_id":"20394767","passages":[{"id":"24718","type":"title","text":["Fear-potentiated startle, but not light-enhanced startle, is enhanced by anxiogenic drugs."],"offsets":[[0,90]]},{"id":"24719","type":"abstract","text":["RATIONALE AND OBJECTIVES: The light-enhanced startle paradigm (LES) is suggested to model anxiety, because of the non-specific cue and the long-term effect. In contrast, the fear-potentiated startle (FPS) is suggested to model conditioned fear. However, the pharmacological profiles of these two paradigms are very similar. The present study investigated the effects of putative anxiogenic drugs on LES and FPS and aimed at determining the sensitivity of LES for anxiogenic drugs and to potentially showing a pharmacological differentiation between these two paradigms. METHODS: Male Wistar rats received each dose of the alpha(2)-adrenoceptor antagonist yohimbine (0.25-1.0mg\/kg), the 5-HT(2C) receptor agonist m-chlorophenylpiperazine (mCPP, 0.5-2.0mg\/kg) or the GABA(A) inverse receptor agonist pentylenetetrazole (PTZ, 3-30mg\/kg) and were subsequently tested in either LES or FPS. RESULTS: None of the drugs enhanced LES, whereas mCPP increased percentage FPS and yohimbine increased absolute FPS values. Furthermore, yohimbine increased baseline startle amplitude in the LES, while mCPP suppressed baseline startle in both the LES and FPS and PTZ suppressed baseline startle in the FPS. CONCLUSIONS: In contrast to findings in the FPS paradigm, none of the drugs were able to exacerbate the LES response. Thus, a clear pharmacological differentiation was found between LES and 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{"id":"24810","document_id":"19203554","passages":[{"id":"24811","type":"title","text":["Proteinase 3-antineutrophil cytoplasmic antibody-(PR3-ANCA) positive necrotizing glomerulonephritis after restarting sulphasalazine treatment."],"offsets":[[0,142]]},{"id":"24812","type":"abstract","text":["A 59-year-old woman with ulcerative colitis developed red eyes, pleural effusion, eosinophilia and urinary abnormalities after restarting of sulphasalazine treatment. Light microscopy of a kidney biopsy revealed segmental necrotizing glomerulonephritis without deposition of immunoglobulin or complement. Proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) titer was elevated at 183 ELISA units (EU) in sera (normal range less than 10 EU), myeloperoxidase-ANCA was negative. PR3-ANCA titer was 250 and 1,070 EU in pleural effusions on right and left side, respectively. Although cessation of sulphasalazine treatment resulted in improvements in fever, red eyes, chest pain, titer of C-reactive protein and volume of the pleural effusions, we initiated steroid therapy, because PR3-ANCA titer rose to 320 EU, eosinophil count increased to 1,100 cells\/microl, and the pleural effusion remained. One month after steroid therapy, the pleural effusion disappeared, and PR3-ANCA titer normalized 3 months later. This case suggests that sulphasalazine can induce PR3-ANCA-positive necrotizing glomerulonephritis."],"offsets":[[143,1256]]}],"entities":[{"id":"24813","type":"Disease","text":["glomerulonephritis"],"offsets":[[81,99]],"normalized":[{"db_name":"MESH","db_id":"D005921"}]},{"id":"24814","type":"Chemical","text":["sulphasalazine"],"offsets":[[117,131]],"normalized":[{"db_name":"MESH","db_id":"D012460"}]},{"id":"24815","type":"Disease","text":["ulcerative colitis"],"offsets":[[168,186]],"normalized":[{"db_name":"MESH","db_id":"D003093"}]},{"id":"24816","type":"Disease","text":["red eyes"],"offsets":[[197,205]],"normalized":[{"db_name":"MESH","db_id":"D005128"}]},{"id":"24817","type":"Disease","text":["pleural effusion"],"offsets":[[207,223]],"normalized":[{"db_name":"MESH","db_id":"D010996"}]},{"id":"24818","type":"Disease","text":["eosinophilia"],"offsets":[[225,237]],"normalized":[{"db_name":"MESH","db_id":"D004802"}]},{"id":"24819","type":"Disease","text":["urinary 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{"id":"24862","document_id":"17049862","passages":[{"id":"24863","type":"title","text":["Is phenytoin administration safe in a hypothermic child?"],"offsets":[[0,56]]},{"id":"24864","type":"abstract","text":["A male neonate with a Chiari malformation and a leaking myelomeningocoele underwent ventriculoperitoneal shunt insertion followed by repair of myelomeningocoele. During anaesthesia and surgery, he inadvertently became moderately hypothermic. Intravenous phenytoin was administered during the later part of the surgery for seizure prophylaxis. Following phenytoin administration, the patient developed acute severe bradycardia, refractory to atropine and adrenaline. The cardiac depressant actions of phenytoin and hypothermia can be additive. Administration of phenytoin in the presence of hypothermia may lead to an adverse cardiac event in children. As phenytoin is a commonly used drug, clinicians need to be aware of this interaction."],"offsets":[[57,795]]}],"entities":[{"id":"24865","type":"Chemical","text":["phenytoin"],"offsets":[[3,12]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"24866","type":"Disease","text":["hypothermic"],"offsets":[[38,49]],"normalized":[{"db_name":"MESH","db_id":"D007035"}]},{"id":"24867","type":"Disease","text":["Chiari malformation"],"offsets":[[79,98]],"normalized":[{"db_name":"MESH","db_id":"D001139"}]},{"id":"24868","type":"Disease","text":["hypothermic"],"offsets":[[286,297]],"normalized":[{"db_name":"MESH","db_id":"D007035"}]},{"id":"24869","type":"Chemical","text":["phenytoin"],"offsets":[[311,320]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"24870","type":"Disease","text":["seizure"],"offsets":[[379,386]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"24871","type":"Chemical","text":["phenytoin"],"offsets":[[410,419]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"24872","type":"Disease","text":["bradycardia"],"offsets":[[471,482]],"normalized":[{"db_name":"MESH","db_id":"D001919"}]},{"id":"24873","type":"Chemical","text":["atropine"],"offsets":[[498,506]],"normalized":[{"db_name":"MESH","db_id":"D001285"}]},{"id":"24874","type":"Chemical","text":["adrenaline"],"offsets":[[511,521]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"24875","type":"Chemical","text":["phenytoin"],"offsets":[[557,566]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"24876","type":"Disease","text":["hypothermia"],"offsets":[[571,582]],"normalized":[{"db_name":"MESH","db_id":"D007035"}]},{"id":"24877","type":"Chemical","text":["phenytoin"],"offsets":[[618,627]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"24878","type":"Disease","text":["hypothermia"],"offsets":[[647,658]],"normalized":[{"db_name":"MESH","db_id":"D007035"}]},{"id":"24879","type":"Chemical","text":["phenytoin"],"offsets":[[712,721]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]}],"events":[],"coreferences":[],"relations":[{"id":"24880","type":"CID","arg1_id":"24865","arg2_id":"24872","normalized":[]},{"id":"24881","type":"CID","arg1_id":"24869","arg2_id":"24872","normalized":[]},{"id":"24882","type":"CID","arg1_id":"24871","arg2_id":"24872","normalized":[]},{"id":"24883","type":"CID","arg1_id":"24875","arg2_id":"24872","normalized":[]},{"id":"24884","type":"CID","arg1_id":"24877","arg2_id":"24872","normalized":[]},{"id":"24885","type":"CID","arg1_id":"24879","arg2_id":"24872","normalized":[]}]}
{"id":"24886","document_id":"16225977","passages":[{"id":"24887","type":"title","text":["Amisulpride related tic-like symptoms in an adolescent schizophrenic."],"offsets":[[0,69]]},{"id":"24888","type":"abstract","text":["Tic disorders can be effectively treated by atypical antipsychotics such as risperidone, olanzapine and ziprasidone. However, there are two case reports that show tic-like symptoms, including motor and phonic variants, occurring during treatment with quetiapine or clozapine. We present a 15-year-old girl schizophrenic who developed frequent involuntary eye-blinking movements after 5 months of amisulpride treatment (1000 mg per day). The tic-like symptoms resolved completely after we reduced the dose of amisulpride down to 800 mg per day. However, her psychosis recurred after the dose reduction. We then placed her on an additional 100 mg per day of quetiapine. She has been in complete remission under the combined medications for more than one year and maintains a fair role function. No more tic-like symptoms or other side effects have been reported. Together with previously reported cases, our patient suggests that tic-like symptoms might occur in certain vulnerable individuals during treatment with atypical antipsychotics such as quetiapine, clozapine, or amisulpride."],"offsets":[[70,1154]]}],"entities":[{"id":"24889","type":"Chemical","text":["Amisulpride"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"C012052"}]},{"id":"24890","type":"Disease","text":["tic-like symptoms"],"offsets":[[20,37]],"normalized":[{"db_name":"MESH","db_id":"D013981"}]},{"id":"24891","type":"Disease","text":["schizophrenic"],"offsets":[[55,68]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"24892","type":"Disease","text":["Tic 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{"id":"24935","document_id":"12852481","passages":[{"id":"24936","type":"title","text":["Comparison of developmental toxicology of aspirin (acetylsalicylic acid) in rats using selected dosing paradigms."],"offsets":[[0,113]]},{"id":"24937","type":"abstract","text":["BACKGROUND: Analysis of the literature for nonsteroidal anti-inflammatory drugs (NSAIDs) suggests that a low incidence of developmental anomalies occurs in rats given NSAIDs on specific days during organogenesis. Aspirin (acetylsalicylic acid [ASA]), an irreversible cyclooxygenase 1 and 2 inhibitor, induces developmental anomalies when administered to Wistar rats on gestational day (GD) 9, 10, or 11 (Kimmel CA, Wilson JG, Schumacher HJ. Teratology 4:15-24, 1971). There are no published ASA studies using the multiple dosing paradigm of GDs 6 to 17. Objectives of the current study were to compare results between Sprague-Dawley (SD) and Wistar strains when ASA is administered on GD 9, 10, or 11; to compare the malformation patterns following single and multiple dosings during organogenesis in SD rats; and to test the hypothesis that maternal gastrointestinal toxicity confounds the detection of low incidence malformations with ASA when a multiple dosing paradigm is used. METHODS: ASA was administered as a single dose on GD 9 (0, 250, 500, or 625 mg\/kg), 10 (0, 500, 625, or 750 mg\/kg), or 11 (0, 500, 750, or 1000 mg\/kg) and from GD 6 to GD 17 (0, 50, 125, or 250 mg\/kg a day) in the multiple dose study to SD rats. Animals were killed on GD 21, and fetuses were examined viscerally. RESULTS: The literature evaluation suggested that NSAIDs induce ventricular septal defects (VSDs) and midline defects (MDs) in rats and diaphragmatic hernia (DH), MDs, and VSDs in rabbits (Cook JC et al., 2003); hence, the present study focused on these malformations, even though ASA induces several other low-incidence malformations. In single dose studies, DH, MD, and VSD were induced on GDs 9 and 10. VSD also was noted following treatment on GD 11. In contrast, DH and MD were noted in the multiple dose study design only in the high-dose group, and VSD was noted across all dose groups. CONCLUSIONS: High concordance in major developmental anomalies between Wistar and SD rats were noted with the exception of VSD in the SD rats and hydrocephalus in the Wistar rats. Variations and malformations were similar when ASA was administered as a single dose or during the period of organogenesis (GDs 6 to 17). It was also evident that, by titrating the dose to achieve a maximum tolerated dose, malformations that normally occur at low incidence, as reported from previous single dose studies, could also be induced with ASA given at multiple doses."],"offsets":[[114,2561]]}],"entities":[{"id":"24938","type":"Chemical","text":["aspirin"],"offsets":[[42,49]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"24939","type":"Chemical","text":["acetylsalicylic acid"],"offsets":[[51,71]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"24940","type":"Disease","text":["developmental anomalies"],"offsets":[[236,259]],"normalized":[{"db_name":"MESH","db_id":"D000014"}]},{"id":"24941","type":"Chemical","text":["Aspirin"],"offsets":[[327,334]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"24942","type":"Chemical","text":["acetylsalicylic 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{"id":"25204","document_id":"11858397","passages":[{"id":"25205","type":"title","text":["Torsade de pointes induced by metoclopramide in an elderly woman with preexisting complete left bundle branch block."],"offsets":[[0,116]]},{"id":"25206","type":"abstract","text":["There is a growing list of drugs implicated in acquired long QT syndrome and torsade de pointes. However, the torsadogenic potential of metoclopramide, a commonly used antiemetic and prokinetic drug, has not been reported in the literature, despite its chemical similarity to procainamide. We report on a 92-year-old woman with preexisting complete left bundle branch block who developed torsade de pointes after intravenous and oral administration of metoclopramide. This patient also developed torsade de pointes when cisapride and erythromycin were given simultaneously. These two episodes were suppressed successfully after discontinuing the offending drugs and administering class IB drugs. This is the first documentation that metoclopramide provokes torsade de pointes clinically. Metoclopramide should be used cautiously in patients with a risk of torsade de pointes."],"offsets":[[117,992]]}],"entities":[{"id":"25207","type":"Disease","text":["Torsade de pointes"],"offsets":[[0,18]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"25208","type":"Chemical","text":["metoclopramide"],"offsets":[[30,44]],"normalized":[{"db_name":"MESH","db_id":"D008787"}]},{"id":"25209","type":"Disease","text":["left bundle branch block"],"offsets":[[91,115]],"normalized":[{"db_name":"MESH","db_id":"D002037"}]},{"id":"25210","type":"Disease","text":["long QT syndrome"],"offsets":[[173,189]],"normalized":[{"db_name":"MESH","db_id":"D008133"}]},{"id":"25211","type":"Disease","text":["torsade de 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{"id":"25266","document_id":"11009181","passages":[{"id":"25267","type":"title","text":["Apomorphine: an underutilized therapy for Parkinson's disease."],"offsets":[[0,62]]},{"id":"25268","type":"abstract","text":["Apomorphine was the first dopaminergic drug ever used to treat symptoms of Parkinson's disease. While powerful antiparkinsonian effects had been observed as early as 1951, the potential of treating fluctuating Parkinson's disease by subcutaneous administration of apomorphine has only recently become the subject of systematic study. A number of small scale clinical trials have unequivocally shown that intermittent subcutaneous apomorphine injections produce antiparkinsonian benefit close if not identical to that seen with levodopa and that apomorphine rescue injections can reliably revert off-periods even in patients with complex on-off motor swings. Continuous subcutaneous apomorphine infusions can reduce daily off-time by more than 50% in this group of patients, which appears to be a stronger effect than that generally seen with add-on therapy with oral dopamine agonists or COMT inhibitors. Extended follow-up studies of up to 8 years have demonstrated long-term persistence of apomorphine efficacy. In addition, there is convincing clinical evidence that monotherapy with continuous subcutaneous apomorphine infusions is associated with marked reductions of preexisting levodopa-induced dyskinesias. The main side effects of subcutaneous apomorphine treatment are related to cutaneous tolerability problems, whereas sedation and psychiatric complications play a lesser role. Given the marked degree of efficacy of subcutaneous apomorphine treatment in fluctuating Parkinson's disease, this approach seems to deserve more widespread clinical use."],"offsets":[[63,1623]]}],"entities":[{"id":"25269","type":"Chemical","text":["Apomorphine"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"25270","type":"Disease","text":["Parkinson's disease"],"offsets":[[42,61]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"25271","type":"Chemical","text":["Apomorphine"],"offsets":[[63,74]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"25272","type":"Disease","text":["Parkinson's disease"],"offsets":[[138,157]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"25273","type":"Disease","text":["Parkinson's disease"],"offsets":[[273,292]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"25274","type":"Chemical","text":["apomorphine"],"offsets":[[327,338]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"25275","type":"Chemical","text":["apomorphine"],"offsets":[[493,504]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"25276","type":"Chemical","text":["levodopa"],"offsets":[[590,598]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"25277","type":"Chemical","text":["apomorphine"],"offsets":[[608,619]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"25278","type":"Chemical","text":["apomorphine"],"offsets":[[745,756]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"25279","type":"Chemical","text":["dopamine"],"offsets":[[930,938]],"normalized":[{"db_name":"MESH","db_id":"D004298"}]},{"id":"25280","type":"Chemical","text":["apomorphine"],"offsets":[[1055,1066]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"25281","type":"Chemical","text":["apomorphine"],"offsets":[[1174,1185]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"25282","type":"Chemical","text":["levodopa"],"offsets":[[1248,1256]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"25283","type":"Disease","text":["dyskinesias"],"offsets":[[1265,1276]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"25284","type":"Chemical","text":["apomorphine"],"offsets":[[1316,1327]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"25285","type":"Disease","text":["psychiatric"],"offsets":[[1407,1418]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"25286","type":"Chemical","text":["apomorphine"],"offsets":[[1505,1516]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"25287","type":"Disease","text":["Parkinson's disease"],"offsets":[[1542,1561]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]}],"events":[],"coreferences":[],"relations":[{"id":"25288","type":"CID","arg1_id":"25276","arg2_id":"25283","normalized":[]},{"id":"25289","type":"CID","arg1_id":"25282","arg2_id":"25283","normalized":[]}]}
{"id":"25290","document_id":"8988571","passages":[{"id":"25291","type":"title","text":["Fatal excited delirium following cocaine use: epidemiologic findings provide new evidence for mechanisms of cocaine toxicity."],"offsets":[[0,125]]},{"id":"25292","type":"abstract","text":["We describe an outbreak of deaths from cocaine-induced excited delirium (EDDs) in Dade County, Florida between 1979 and 1990. From a registry of all cocaine-related deaths in Dade County, Florida, from 1969-1990, 58 EDDs were compared with 125 victims of accidental cocaine overdose without excited delirium. Compared with controls, EDDs were more frequently black, male, and younger. They were less likely to have a low body mass index, and more likely to have died in police custody, to have received medical treatment immediately before death, to have survived for a longer period, to have developed hyperthermia, and to have died in summer months. EDDs had concentrations of cocaine and benzoylecgonine in autopsy blood that were similar to those for controls. The epidemiologic findings are most consistent with the hypothesis that chronic cocaine use disrupts dopaminergic function and, when coupled with recent cocaine use, may precipitate agitation, delirium, aberrant thermoregulation, rhabdomyolysis, and sudden death."],"offsets":[[126,1154]]}],"entities":[{"id":"25293","type":"Disease","text":["delirium"],"offsets":[[14,22]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"25294","type":"Chemical","text":["cocaine"],"offsets":[[33,40]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"25295","type":"Chemical","text":["cocaine"],"offsets":[[108,115]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"25296","type":"Disease","text":["toxicity"],"offsets":[[116,124]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"25297","type":"Chemical","text":["cocaine"],"offsets":[[165,172]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"25298","type":"Disease","text":["delirium"],"offsets":[[189,197]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"25299","type":"Disease","text":["EDDs"],"offsets":[[199,203]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"25300","type":"Chemical","text":["cocaine"],"offsets":[[275,282]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"25301","type":"Disease","text":["EDDs"],"offsets":[[342,346]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"25302","type":"Chemical","text":["cocaine"],"offsets":[[392,399]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"25303","type":"Disease","text":["overdose"],"offsets":[[400,408]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"25304","type":"Disease","text":["delirium"],"offsets":[[425,433]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"25305","type":"Disease","text":["EDDs"],"offsets":[[459,463]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"25306","type":"Disease","text":["hyperthermia"],"offsets":[[729,741]],"normalized":[{"db_name":"MESH","db_id":"D005334"}]},{"id":"25307","type":"Disease","text":["EDDs"],"offsets":[[778,782]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"25308","type":"Chemical","text":["cocaine"],"offsets":[[805,812]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"25309","type":"Chemical","text":["benzoylecgonine"],"offsets":[[817,832]],"normalized":[{"db_name":"MESH","db_id":"C005618"}]},{"id":"25310","type":"Chemical","text":["cocaine"],"offsets":[[971,978]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"25311","type":"Chemical","text":["cocaine"],"offsets":[[1044,1051]],"normalized":[{"db_name":"MESH","db_id":"D003042"}]},{"id":"25312","type":"Disease","text":["agitation"],"offsets":[[1073,1082]],"normalized":[{"db_name":"MESH","db_id":"D011595"}]},{"id":"25313","type":"Disease","text":["delirium"],"offsets":[[1084,1092]],"normalized":[{"db_name":"MESH","db_id":"D003693"}]},{"id":"25314","type":"Disease","text":["rhabdomyolysis"],"offsets":[[1121,1135]],"normalized":[{"db_name":"MESH","db_id":"D012206"}]},{"id":"25315","type":"Disease","text":["sudden 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{"id":"25396","document_id":"6615052","passages":[{"id":"25397","type":"title","text":["Heparin-induced thrombocytopenia, thrombosis, and hemorrhage."],"offsets":[[0,61]]},{"id":"25398","type":"abstract","text":["Sixty-two patients with a heparin-induced thrombocytopenia are reported. Clinical manifestations of this disorder include hemorrhage or, more frequently, thromboembolic events in patients receiving heparin. Laboratory testing has revealed a falling platelet count, increased resistance to heparin, and aggregation of platelets by the patient's plasma when heparin is added. Immunologic testing has demonstrated the presence of a heparin-dependent platelet membrane antibody. The 20 deaths, 52 hemorrhagic and thromboembolic complications, and 21 surgical procedures to manage the complications confirm the seriousness of the disorder. Specific risk factors have not been identified; therefore, all patients receiving heparin should be monitored. If the platelet count falls to less than 100,000\/mm3, while the patient is receiving heparin, platelet aggregation testing, using the patient's plasma, is indicated. Management consists of cessation of heparin, platelet anti-aggregating agents, and alternate forms of anticoagulation when 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{"id":"25500","document_id":"3952818","passages":[{"id":"25501","type":"title","text":["Cardiac toxicity of 5-fluorouracil. Report of a case of spontaneous angina."],"offsets":[[0,75]]},{"id":"25502","type":"abstract","text":["We report a case of a patient with colon carcinoma and liver metastasis who presented chest pain after 5-fluorouracil (5-FU) administration. Clinical electrocardiographic evolution was similar to that observed in Prinzmetal's angina, and chest pain promptly resolved with nifedipine. These data suggest that coronary spasm may be the cause of cardiotoxicity due to 5-FU, and that calcium antagonists may probably be used in the prevention or treatment of 5-FU cardiotoxicity."],"offsets":[[76,551]]}],"entities":[{"id":"25503","type":"Disease","text":["Cardiac toxicity"],"offsets":[[0,16]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"25504","type":"Chemical","text":["5-fluorouracil"],"offsets":[[20,34]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"25505","type":"Disease","text":["angina"],"offsets":[[68,74]],"normalized":[{"db_name":"MESH","db_id":"D000787"}]},{"id":"25506","type":"Disease","text":["colon carcinoma"],"offsets":[[111,126]],"normalized":[{"db_name":"MESH","db_id":"D003110"}]},{"id":"25507","type":"Disease","text":["metastasis"],"offsets":[[137,147]],"normalized":[{"db_name":"MESH","db_id":"D009362"}]},{"id":"25508","type":"Disease","text":["chest pain"],"offsets":[[162,172]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"25509","type":"Chemical","text":["5-fluorouracil"],"offsets":[[179,193]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"25510","type":"Chemical","text":["5-FU"],"offsets":[[195,199]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"25511","type":"Disease","text":["Prinzmetal's angina"],"offsets":[[289,308]],"normalized":[{"db_name":"MESH","db_id":"D000788"}]},{"id":"25512","type":"Disease","text":["chest pain"],"offsets":[[314,324]],"normalized":[{"db_name":"MESH","db_id":"D002637"}]},{"id":"25513","type":"Chemical","text":["nifedipine"],"offsets":[[348,358]],"normalized":[{"db_name":"MESH","db_id":"D009543"}]},{"id":"25514","type":"Disease","text":["coronary spasm"],"offsets":[[384,398]],"normalized":[{"db_name":"MESH","db_id":"D003329"}]},{"id":"25515","type":"Disease","text":["cardiotoxicity"],"offsets":[[419,433]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"25516","type":"Chemical","text":["5-FU"],"offsets":[[441,445]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"25517","type":"Chemical","text":["calcium"],"offsets":[[456,463]],"normalized":[{"db_name":"MESH","db_id":"D002118"}]},{"id":"25518","type":"Chemical","text":["5-FU"],"offsets":[[531,535]],"normalized":[{"db_name":"MESH","db_id":"D005472"}]},{"id":"25519","type":"Disease","text":["cardiotoxicity"],"offsets":[[536,550]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]}],"events":[],"coreferences":[],"relations":[{"id":"25520","type":"CID","arg1_id":"25504","arg2_id":"25508","normalized":[]},{"id":"25521","type":"CID","arg1_id":"25504","arg2_id":"25512","normalized":[]},{"id":"25522","type":"CID","arg1_id":"25509","arg2_id":"25508","normalized":[]},{"id":"25523","type":"CID","arg1_id":"25509","arg2_id":"25512","normalized":[]},{"id":"25524","type":"CID","arg1_id":"25510","arg2_id":"25508","normalized":[]},{"id":"25525","type":"CID","arg1_id":"25510","arg2_id":"25512","normalized":[]},{"id":"25526","type":"CID","arg1_id":"25516","arg2_id":"25508","normalized":[]},{"id":"25527","type":"CID","arg1_id":"25516","arg2_id":"25512","normalized":[]},{"id":"25528","type":"CID","arg1_id":"25518","arg2_id":"25508","normalized":[]},{"id":"25529","type":"CID","arg1_id":"25518","arg2_id":"25512","normalized":[]},{"id":"25530","type":"CID","arg1_id":"25504","arg2_id":"25511","normalized":[]},{"id":"25531","type":"CID","arg1_id":"25509","arg2_id":"25511","normalized":[]},{"id":"25532","type":"CID","arg1_id":"25510","arg2_id":"25511","normalized":[]},{"id":"25533","type":"CID","arg1_id":"25516","arg2_id":"25511","normalized":[]},{"id":"25534","type":"CID","arg1_id":"25518","arg2_id":"25511","normalized":[]}]}
{"id":"25535","document_id":"3084782","passages":[{"id":"25536","type":"title","text":["Toxicity due to remission inducing drugs in rheumatoid arthritis. Association with HLA-B35 and Cw4 antigens."],"offsets":[[0,108]]},{"id":"25537","type":"abstract","text":["Twenty-five patients with rheumatoid arthritis (RA) who developed toxicity while taking remission inducing drugs and 30 without toxicity were studied for possible associations with class I and II HLA antigens. A strong association has been found between nephritis and dermatitis due to Tiopronin (a D-Penicillamine like compound) and class I antigens B35-Cw4, and between dermatitis due to gold thiosulphate and B35. Compared to healthy controls a lower DR5 frequency was observed in patients with RA except for the Tiopronin related nephritis group."],"offsets":[[109,659]]}],"entities":[{"id":"25538","type":"Disease","text":["Toxicity"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"25539","type":"Disease","text":["rheumatoid arthritis"],"offsets":[[44,64]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"25540","type":"Disease","text":["rheumatoid arthritis"],"offsets":[[135,155]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"25541","type":"Disease","text":["RA"],"offsets":[[157,159]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"25542","type":"Disease","text":["toxicity"],"offsets":[[175,183]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"25543","type":"Disease","text":["toxicity"],"offsets":[[237,245]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"25544","type":"Disease","text":["nephritis"],"offsets":[[363,372]],"normalized":[{"db_name":"MESH","db_id":"D009393"}]},{"id":"25545","type":"Disease","text":["dermatitis"],"offsets":[[377,387]],"normalized":[{"db_name":"MESH","db_id":"D003872"}]},{"id":"25546","type":"Chemical","text":["Tiopronin"],"offsets":[[395,404]],"normalized":[{"db_name":"MESH","db_id":"D008625"}]},{"id":"25547","type":"Chemical","text":["D-Penicillamine"],"offsets":[[408,423]],"normalized":[{"db_name":"MESH","db_id":"D010396"}]},{"id":"25548","type":"Disease","text":["dermatitis"],"offsets":[[481,491]],"normalized":[{"db_name":"MESH","db_id":"D003872"}]},{"id":"25549","type":"Chemical","text":["gold"],"offsets":[[499,503]],"normalized":[{"db_name":"MESH","db_id":"D006046"}]},{"id":"25550","type":"Chemical","text":["thiosulphate"],"offsets":[[504,516]],"normalized":[]},{"id":"25551","type":"Disease","text":["RA"],"offsets":[[607,609]],"normalized":[{"db_name":"MESH","db_id":"D001172"}]},{"id":"25552","type":"Chemical","text":["Tiopronin"],"offsets":[[625,634]],"normalized":[{"db_name":"MESH","db_id":"D008625"}]},{"id":"25553","type":"Disease","text":["nephritis"],"offsets":[[643,652]],"normalized":[{"db_name":"MESH","db_id":"D009393"}]}],"events":[],"coreferences":[],"relations":[{"id":"25554","type":"CID","arg1_id":"25549","arg2_id":"25545","normalized":[]},{"id":"25555","type":"CID","arg1_id":"25549","arg2_id":"25548","normalized":[]},{"id":"25556","type":"CID","arg1_id":"25546","arg2_id":"25544","normalized":[]},{"id":"25557","type":"CID","arg1_id":"25546","arg2_id":"25553","normalized":[]},{"id":"25558","type":"CID","arg1_id":"25552","arg2_id":"25544","normalized":[]},{"id":"25559","type":"CID","arg1_id":"25552","arg2_id":"25553","normalized":[]},{"id":"25560","type":"CID","arg1_id":"25546","arg2_id":"25545","normalized":[]},{"id":"25561","type":"CID","arg1_id":"25546","arg2_id":"25548","normalized":[]},{"id":"25562","type":"CID","arg1_id":"25552","arg2_id":"25545","normalized":[]},{"id":"25563","type":"CID","arg1_id":"25552","arg2_id":"25548","normalized":[]}]}
{"id":"25564","document_id":"430165","passages":[{"id":"25565","type":"title","text":["Transient hemiparesis: a rare manifestation of diphenylhydantoin toxicity. Report of two cases."],"offsets":[[0,95]]},{"id":"25566","type":"abstract","text":["Among the common side effects of diphenylhydantoin (DPH) overdose, the most frequently encountered neurological signs are those of cerebellar dysfunction. Very rarely, the toxic neurological manifestations of this drug are of cerebral origin. Two patients are presented who suffered progressive hemiparesis due to DPH overdose. Both had brain surgery before DPH treatment. It is assumed that patients with some cerebral damage are liable to manifest DPH toxicity as focal neurological signs."],"offsets":[[96,587]]}],"entities":[{"id":"25567","type":"Disease","text":["hemiparesis"],"offsets":[[10,21]],"normalized":[{"db_name":"MESH","db_id":"D010291"}]},{"id":"25568","type":"Chemical","text":["diphenylhydantoin"],"offsets":[[47,64]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"25569","type":"Disease","text":["toxicity"],"offsets":[[65,73]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"25570","type":"Chemical","text":["diphenylhydantoin"],"offsets":[[129,146]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"25571","type":"Chemical","text":["DPH"],"offsets":[[148,151]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"25572","type":"Disease","text":["overdose"],"offsets":[[153,161]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"25573","type":"Disease","text":["cerebellar dysfunction"],"offsets":[[227,249]],"normalized":[{"db_name":"MESH","db_id":"D002526"}]},{"id":"25574","type":"Disease","text":["hemiparesis"],"offsets":[[391,402]],"normalized":[{"db_name":"MESH","db_id":"D010291"}]},{"id":"25575","type":"Chemical","text":["DPH"],"offsets":[[410,413]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"25576","type":"Disease","text":["overdose"],"offsets":[[414,422]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"25577","type":"Chemical","text":["DPH"],"offsets":[[454,457]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"25578","type":"Disease","text":["cerebral damage"],"offsets":[[507,522]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"25579","type":"Chemical","text":["DPH"],"offsets":[[546,549]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"25580","type":"Disease","text":["toxicity"],"offsets":[[550,558]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]}],"events":[],"coreferences":[],"relations":[{"id":"25581","type":"CID","arg1_id":"25568","arg2_id":"25572","normalized":[]},{"id":"25582","type":"CID","arg1_id":"25568","arg2_id":"25576","normalized":[]},{"id":"25583","type":"CID","arg1_id":"25570","arg2_id":"25572","normalized":[]},{"id":"25584","type":"CID","arg1_id":"25570","arg2_id":"25576","normalized":[]},{"id":"25585","type":"CID","arg1_id":"25571","arg2_id":"25572","normalized":[]},{"id":"25586","type":"CID","arg1_id":"25571","arg2_id":"25576","normalized":[]},{"id":"25587","type":"CID","arg1_id":"25575","arg2_id":"25572","normalized":[]},{"id":"25588","type":"CID","arg1_id":"25575","arg2_id":"25576","normalized":[]},{"id":"25589","type":"CID","arg1_id":"25577","arg2_id":"25572","normalized":[]},{"id":"25590","type":"CID","arg1_id":"25577","arg2_id":"25576","normalized":[]},{"id":"25591","type":"CID","arg1_id":"25579","arg2_id":"25572","normalized":[]},{"id":"25592","type":"CID","arg1_id":"25579","arg2_id":"25576","normalized":[]},{"id":"25593","type":"CID","arg1_id":"25568","arg2_id":"25573","normalized":[]},{"id":"25594","type":"CID","arg1_id":"25570","arg2_id":"25573","normalized":[]},{"id":"25595","type":"CID","arg1_id":"25571","arg2_id":"25573","normalized":[]},{"id":"25596","type":"CID","arg1_id":"25575","arg2_id":"25573","normalized":[]},{"id":"25597","type":"CID","arg1_id":"25577","arg2_id":"25573","normalized":[]},{"id":"25598","type":"CID","arg1_id":"25579","arg2_id":"25573","normalized":[]},{"id":"25599","type":"CID","arg1_id":"25568","arg2_id":"25567","normalized":[]},{"id":"25600","type":"CID","arg1_id":"25568","arg2_id":"25574","normalized":[]},{"id":"25601","type":"CID","arg1_id":"25570","arg2_id":"25567","normalized":[]},{"id":"25602","type":"CID","arg1_id":"25570","arg2_id":"25574","normalized":[]},{"id":"25603","type":"CID","arg1_id":"25571","arg2_id":"25567","normalized":[]},{"id":"25604","type":"CID","arg1_id":"25571","arg2_id":"25574","normalized":[]},{"id":"25605","type":"CID","arg1_id":"25575","arg2_id":"25567","normalized":[]},{"id":"25606","type":"CID","arg1_id":"25575","arg2_id":"25574","normalized":[]},{"id":"25607","type":"CID","arg1_id":"25577","arg2_id":"25567","normalized":[]},{"id":"25608","type":"CID","arg1_id":"25577","arg2_id":"25574","normalized":[]},{"id":"25609","type":"CID","arg1_id":"25579","arg2_id":"25567","normalized":[]},{"id":"25610","type":"CID","arg1_id":"25579","arg2_id":"25574","normalized":[]}]}
{"id":"25611","document_id":"16600756","passages":[{"id":"25612","type":"title","text":["Nerve growth factor and prostaglandins in the urine of female patients with overactive bladder."],"offsets":[[0,95]]},{"id":"25613","type":"abstract","text":["PURPOSE: NGF and PGs in the bladder can be affected by pathological changes in the bladder and these changes can be detected in urine. We investigated changes in urinary NGF and PGs in women with OAB. MATERIALS AND METHODS: The study groups included 65 women with OAB and 20 without bladder symptoms who served as controls. Evaluation included patient history, urinalysis, a voiding diary and urodynamic studies. Urine samples were collected. NGF, PGE2, PGF2alpha and PGI2 were measured using enzyme-linked immunosorbent assay and compared between the groups. In addition, correlations between urinary NGF and PG, and urodynamic parameters in patients with OAB were examined. RESULTS: Urinary NGF, PGE2 and PGF2alpha were significantly increased in patients with OAB compared with controls (p <0.05). However, urinary PGI2 was not different between controls and patients with OAB. In patients with OAB urinary PGE2 positively correlated with volume at first desire to void and maximum cystometric capacity (p <0.05). Urinary NGF, PGF2alpha and PGI2 did not correlate with urodynamic parameters in patients with OAB. CONCLUSIONS: NGF and PGs have important roles in the development of OAB symptoms in female patients. Urinary levels of these factors may be used as markers to evaluate OAB symptoms."],"offsets":[[96,1393]]}],"entities":[{"id":"25614","type":"Chemical","text":["prostaglandins"],"offsets":[[24,38]],"normalized":[{"db_name":"MESH","db_id":"D011453"}]},{"id":"25615","type":"Disease","text":["overactive bladder"],"offsets":[[76,94]],"normalized":[{"db_name":"MESH","db_id":"D053201"}]},{"id":"25616","type":"Chemical","text":["PGs"],"offsets":[[113,116]],"normalized":[{"db_name":"MESH","db_id":"D011453"}]},{"id":"25617","type":"Chemical","text":["PGs"],"offsets":[[274,277]],"normalized":[{"db_name":"MESH","db_id":"D011453"}]},{"id":"25618","type":"Disease","text":["OAB"],"offsets":[[292,295]],"normalized":[{"db_name":"MESH","db_id":"D053201"}]},{"id":"25619","type":"Disease","text":["OAB"],"offsets":[[360,363]],"normalized":[{"db_name":"MESH","db_id":"D053201"}]},{"id":"25620","type":"Chemical","text":["PGE2"],"offsets":[[544,548]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"25621","type":"Chemical","text":["PGF2alpha"],"offsets":[[550,559]],"normalized":[{"db_name":"MESH","db_id":"D015237"}]},{"id":"25622","type":"Chemical","text":["PGI2"],"offsets":[[564,568]],"normalized":[{"db_name":"MESH","db_id":"D011464"}]},{"id":"25623","type":"Chemical","text":["PG"],"offsets":[[706,708]],"normalized":[{"db_name":"MESH","db_id":"D011453"}]},{"id":"25624","type":"Disease","text":["OAB"],"offsets":[[753,756]],"normalized":[{"db_name":"MESH","db_id":"D053201"}]},{"id":"25625","type":"Chemical","text":["PGE2"],"offsets":[[794,798]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"25626","type":"Chemical","text":["PGF2alpha"],"offsets":[[803,812]],"normalized":[{"db_name":"MESH","db_id":"D015237"}]},{"id":"25627","type":"Disease","text":["OAB"],"offsets":[[859,862]],"normalized":[{"db_name":"MESH","db_id":"D053201"}]},{"id":"25628","type":"Chemical","text":["PGI2"],"offsets":[[914,918]],"normalized":[{"db_name":"MESH","db_id":"D011464"}]},{"id":"25629","type":"Disease","text":["OAB"],"offsets":[[972,975]],"normalized":[{"db_name":"MESH","db_id":"D053201"}]},{"id":"25630","type":"Disease","text":["OAB"],"offsets":[[994,997]],"normalized":[{"db_name":"MESH","db_id":"D053201"}]},{"id":"25631","type":"Chemical","text":["PGE2"],"offsets":[[1006,1010]],"normalized":[{"db_name":"MESH","db_id":"D015232"}]},{"id":"25632","type":"Chemical","text":["PGF2alpha"],"offsets":[[1126,1135]],"normalized":[{"db_name":"MESH","db_id":"D015237"}]},{"id":"25633","type":"Chemical","text":["PGI2"],"offsets":[[1140,1144]],"normalized":[{"db_name":"MESH","db_id":"D011464"}]},{"id":"25634","type":"Disease","text":["OAB"],"offsets":[[1207,1210]],"normalized":[{"db_name":"MESH","db_id":"D053201"}]},{"id":"25635","type":"Chemical","text":["PGs"],"offsets":[[1233,1236]],"normalized":[{"db_name":"MESH","db_id":"D011453"}]},{"id":"25636","type":"Disease","text":["OAB"],"offsets":[[1280,1283]],"normalized":[{"db_name":"MESH","db_id":"D053201"}]},{"id":"25637","type":"Disease","text":["OAB"],"offsets":[[1380,1383]],"normalized":[{"db_name":"MESH","db_id":"D053201"}]}],"events":[],"coreferences":[],"relations":[{"id":"25638","type":"CID","arg1_id":"25621","arg2_id":"25615","normalized":[]},{"id":"25639","type":"CID","arg1_id":"25621","arg2_id":"25618","normalized":[]},{"id":"25640","type":"CID","arg1_id":"25621","arg2_id":"25619","normalized":[]},{"id":"25641","type":"CID","arg1_id":"25621","arg2_id":"25624","normalized":[]},{"id":"25642","type":"CID","arg1_id":"25621","arg2_id":"25627","normalized":[]},{"id":"25643","type":"CID","arg1_id":"25621","arg2_id":"25629","normalized":[]},{"id":"25644","type":"CID","arg1_id":"25621","arg2_id":"25630","normalized":[]},{"id":"25645","type":"CID","arg1_id":"25621","arg2_id":"25634","normalized":[]},{"id":"25646","type":"CID","arg1_id":"25621","arg2_id":"25636","normalized":[]},{"id":"25647","type":"CID","arg1_id":"25621","arg2_id":"25637","normalized":[]},{"id":"25648","type":"CID","arg1_id":"25626","arg2_id":"25615","normalized":[]},{"id":"25649","type":"CID","arg1_id":"25626","arg2_id":"25618","normalized":[]},{"id":"25650","type":"CID","arg1_id":"25626","arg2_id":"25619","normalized":[]},{"id":"25651","type":"CID","arg1_id":"25626","arg2_id":"25624","normalized":[]},{"id":"25652","type":"CID","arg1_id":"25626","arg2_id":"25627","normalized":[]},{"id":"25653","type":"CID","arg1_id":"25626","arg2_id":"25629","normalized":[]},{"id":"25654","type":"CID","arg1_id":"25626","arg2_id":"25630","normalized":[]},{"id":"25655","type":"CID","arg1_id":"25626","arg2_id":"25634","normalized":[]},{"id":"25656","type":"CID","arg1_id":"25626","arg2_id":"25636","normalized":[]},{"id":"25657","type":"CID","arg1_id":"25626","arg2_id":"25637","normalized":[]},{"id":"25658","type":"CID","arg1_id":"25632","arg2_id":"25615","normalized":[]},{"id":"25659","type":"CID","arg1_id":"25632","arg2_id":"25618","normalized":[]},{"id":"25660","type":"CID","arg1_id":"25632","arg2_id":"25619","normalized":[]},{"id":"25661","type":"CID","arg1_id":"25632","arg2_id":"25624","normalized":[]},{"id":"25662","type":"CID","arg1_id":"25632","arg2_id":"25627","normalized":[]},{"id":"25663","type":"CID","arg1_id":"25632","arg2_id":"25629","normalized":[]},{"id":"25664","type":"CID","arg1_id":"25632","arg2_id":"25630","normalized":[]},{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{"id":"25698","document_id":"15686794","passages":[{"id":"25699","type":"title","text":["Acute low back pain during intravenous administration of amiodarone: a report of two cases."],"offsets":[[0,91]]},{"id":"25700","type":"abstract","text":["Amiodarone represents an effective antiarrhythmic drug for cardioversion of recent-onset atrial fibrillation (AF) and maintenance of sinus rhythm. We briefly describe two patients suffering from recent-onset atrial fibrillation, who experienced an acute devastating low back pain a few minutes after initiation of intravenous amiodarone loading. Notably, this side effect has not been ever reported in the medical literature. Clinicians should be aware of this reaction since prompt termination of parenteral administration leads to complete resolution."],"offsets":[[92,645]]}],"entities":[{"id":"25701","type":"Disease","text":["low back pain"],"offsets":[[6,19]],"normalized":[{"db_name":"MESH","db_id":"D017116"}]},{"id":"25702","type":"Chemical","text":["amiodarone"],"offsets":[[57,67]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"25703","type":"Chemical","text":["Amiodarone"],"offsets":[[92,102]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"25704","type":"Disease","text":["atrial fibrillation"],"offsets":[[181,200]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"25705","type":"Disease","text":["AF"],"offsets":[[202,204]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"25706","type":"Disease","text":["atrial fibrillation"],"offsets":[[300,319]],"normalized":[{"db_name":"MESH","db_id":"D001281"}]},{"id":"25707","type":"Disease","text":["low back pain"],"offsets":[[358,371]],"normalized":[{"db_name":"MESH","db_id":"D017116"}]},{"id":"25708","type":"Chemical","text":["amiodarone"],"offsets":[[418,428]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]}],"events":[],"coreferences":[],"relations":[{"id":"25709","type":"CID","arg1_id":"25702","arg2_id":"25701","normalized":[]},{"id":"25710","type":"CID","arg1_id":"25702","arg2_id":"25707","normalized":[]},{"id":"25711","type":"CID","arg1_id":"25703","arg2_id":"25701","normalized":[]},{"id":"25712","type":"CID","arg1_id":"25703","arg2_id":"25707","normalized":[]},{"id":"25713","type":"CID","arg1_id":"25708","arg2_id":"25701","normalized":[]},{"id":"25714","type":"CID","arg1_id":"25708","arg2_id":"25707","normalized":[]}]}
{"id":"25715","document_id":"12760988","passages":[{"id":"25716","type":"title","text":["Postoperative myalgia after succinylcholine: no evidence for an inflammatory origin."],"offsets":[[0,84]]},{"id":"25717","type":"abstract","text":["A common side effect associated with succinylcholine is postoperative myalgia. The pathogenesis of this myalgia is still unclear; inflammation has been suggested but without convincing evidence. We designed the present study to investigate whether an inflammatory reaction contributes to this myalgia. The incidence and severity of succinylcholine-associated myalgia was determined in 64 patients pretreated with saline or dexamethasone before succinylcholine (n = 32 for each). Incidence and severity of myalgia did not differ significantly between the two groups: 15 patients in the dexamethasone group complained of myalgia compared with 18 patients in the saline group, and severe myalgia was reported by five patients and three patients, respectively (not significant). At 48 h after surgery, 12 patients in both groups still suffered from myalgia (not significant). In addition, interleukin-6 (IL-6) as an early marker of inflammation was assessed in a subgroup of 10 patients pretreated with saline. We found an increase of IL-6 for only three patients, but only one patient reported myalgia; no relationship between myalgia and the increase of IL-6 was found. In conclusion, there is no evidence for an inflammatory origin of succinylcholine-associated myalgia. IMPLICATIONS: Administration of dexamethasone before succinylcholine was not effective in decreasing the incidence or the severity of succinylcholine-induced postoperative myalgia. Furthermore, there was no significant relationship between postoperative myalgia and time course of interleukin-6 concentrations, a marker of inflammation. Pretreatment with dexamethasone is not justified to prevent postoperative myalgia after succinylcholine."],"offsets":[[85,1796]]}],"entities":[{"id":"25718","type":"Disease","text":["Postoperative myalgia"],"offsets":[[0,21]],"normalized":[{"db_name":"MESH","db_id":"D010149"}]},{"id":"25719","type":"Chemical","text":["succinylcholine"],"offsets":[[28,43]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"25720","type":"Chemical","text":["succinylcholine"],"offsets":[[122,137]],"normalized":[{"db_name":"MESH","db_id":"D013390"}]},{"id":"25721","type":"Disease","text":["postoperative 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{"id":"25868","document_id":"12691807","passages":[{"id":"25869","type":"title","text":["Levodopa-induced oromandibular dystonia in progressive supranuclear palsy."],"offsets":[[0,74]]},{"id":"25870","type":"abstract","text":["Levodopa-induced dyskinesias have been reported in Parkinson's disease and multiple system atrophy. Cranial dystonias are rare in patients with progressive supranuclear palsy (PSP). In this report we describe an unusual case of reversible levodopa-induced Oromandibular dystonia (OMD) in a PSP patient to highlight the importance of recognizing this drug related complication in the management of PSP, and discuss the possible underlying pathophysiology."],"offsets":[[75,529]]}],"entities":[{"id":"25871","type":"Chemical","text":["Levodopa"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"25872","type":"Disease","text":["dystonia"],"offsets":[[31,39]],"normalized":[{"db_name":"MESH","db_id":"D004421"}]},{"id":"25873","type":"Disease","text":["progressive supranuclear palsy"],"offsets":[[43,73]],"normalized":[{"db_name":"MESH","db_id":"D013494"}]},{"id":"25874","type":"Chemical","text":["Levodopa"],"offsets":[[75,83]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"25875","type":"Disease","text":["dyskinesias"],"offsets":[[92,103]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"25876","type":"Disease","text":["Parkinson's disease"],"offsets":[[126,145]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"25877","type":"Disease","text":["multiple system atrophy"],"offsets":[[150,173]],"normalized":[{"db_name":"MESH","db_id":"D019578"}]},{"id":"25878","type":"Disease","text":["dystonias"],"offsets":[[183,192]],"normalized":[{"db_name":"MESH","db_id":"D004421"}]},{"id":"25879","type":"Disease","text":["progressive supranuclear palsy"],"offsets":[[219,249]],"normalized":[{"db_name":"MESH","db_id":"D013494"}]},{"id":"25880","type":"Disease","text":["PSP"],"offsets":[[251,254]],"normalized":[{"db_name":"MESH","db_id":"D013494"}]},{"id":"25881","type":"Chemical","text":["levodopa"],"offsets":[[314,322]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"25882","type":"Disease","text":["Oromandibular dystonia"],"offsets":[[331,353]],"normalized":[{"db_name":"MESH","db_id":"D008538"}]},{"id":"25883","type":"Disease","text":["OMD"],"offsets":[[355,358]],"normalized":[{"db_name":"MESH","db_id":"D008538"}]},{"id":"25884","type":"Disease","text":["PSP"],"offsets":[[365,368]],"normalized":[{"db_name":"MESH","db_id":"D013494"}]},{"id":"25885","type":"Disease","text":["PSP"],"offsets":[[472,475]],"normalized":[{"db_name":"MESH","db_id":"D013494"}]}],"events":[],"coreferences":[],"relations":[{"id":"25886","type":"CID","arg1_id":"25871","arg2_id":"25872","normalized":[]},{"id":"25887","type":"CID","arg1_id":"25871","arg2_id":"25878","normalized":[]},{"id":"25888","type":"CID","arg1_id":"25874","arg2_id":"25872","normalized":[]},{"id":"25889","type":"CID","arg1_id":"25874","arg2_id":"25878","normalized":[]},{"id":"25890","type":"CID","arg1_id":"25881","arg2_id":"25872","normalized":[]},{"id":"25891","type":"CID","arg1_id":"25881","arg2_id":"25878","normalized":[]}]}
{"id":"25892","document_id":"12600698","passages":[{"id":"25893","type":"title","text":["Protective effect of edaravone against streptomycin-induced vestibulotoxicity in the guinea pig."],"offsets":[[0,96]]},{"id":"25894","type":"abstract","text":["This study investigated alleviation of streptomycin-induced vestibulotoxicity by edaravone in guinea pigs. Edaravone, a free radical scavenger, has potent free radical quenching action and is used in clinical practice to treat cerebral infarction. Streptomycin was administered to the inner ear by osmotic pump for 24 h, and edaravone (n=8) or saline (n=6) was intraperitoneally injected once a day for 7 days. We observed horizontal vestibulo-ocular reflex as a marker of postoperative vestibular function. Animals injected with saline showed statistically smaller gains than those injected with edaravone. These results suggest that edaravone suppresses streptomycin-induced vestibulotoxicity."],"offsets":[[97,792]]}],"entities":[{"id":"25895","type":"Chemical","text":["edaravone"],"offsets":[[21,30]],"normalized":[{"db_name":"MESH","db_id":"C005435"}]},{"id":"25896","type":"Chemical","text":["streptomycin"],"offsets":[[39,51]],"normalized":[{"db_name":"MESH","db_id":"D013307"}]},{"id":"25897","type":"Disease","text":["vestibulotoxicity"],"offsets":[[60,77]],"normalized":[{"db_name":"MESH","db_id":"D015837"}]},{"id":"25898","type":"Chemical","text":["streptomycin"],"offsets":[[136,148]],"normalized":[{"db_name":"MESH","db_id":"D013307"}]},{"id":"25899","type":"Disease","text":["vestibulotoxicity"],"offsets":[[157,174]],"normalized":[{"db_name":"MESH","db_id":"D015837"}]},{"id":"25900","type":"Chemical","text":["edaravone"],"offsets":[[178,187]],"normalized":[{"db_name":"MESH","db_id":"C005435"}]},{"id":"25901","type":"Chemical","text":["Edaravone"],"offsets":[[204,213]],"normalized":[{"db_name":"MESH","db_id":"C005435"}]},{"id":"25902","type":"Disease","text":["cerebral infarction"],"offsets":[[324,343]],"normalized":[{"db_name":"MESH","db_id":"D002544"}]},{"id":"25903","type":"Chemical","text":["Streptomycin"],"offsets":[[345,357]],"normalized":[{"db_name":"MESH","db_id":"D013307"}]},{"id":"25904","type":"Chemical","text":["edaravone"],"offsets":[[422,431]],"normalized":[{"db_name":"MESH","db_id":"C005435"}]},{"id":"25905","type":"Chemical","text":["edaravone"],"offsets":[[694,703]],"normalized":[{"db_name":"MESH","db_id":"C005435"}]},{"id":"25906","type":"Chemical","text":["edaravone"],"offsets":[[732,741]],"normalized":[{"db_name":"MESH","db_id":"C005435"}]},{"id":"25907","type":"Chemical","text":["streptomycin"],"offsets":[[753,765]],"normalized":[{"db_name":"MESH","db_id":"D013307"}]},{"id":"25908","type":"Disease","text":["vestibulotoxicity"],"offsets":[[774,791]],"normalized":[{"db_name":"MESH","db_id":"D015837"}]}],"events":[],"coreferences":[],"relations":[{"id":"25909","type":"CID","arg1_id":"25896","arg2_id":"25897","normalized":[]},{"id":"25910","type":"CID","arg1_id":"25896","arg2_id":"25899","normalized":[]},{"id":"25911","type":"CID","arg1_id":"25896","arg2_id":"25908","normalized":[]},{"id":"25912","type":"CID","arg1_id":"25898","arg2_id":"25897","normalized":[]},{"id":"25913","type":"CID","arg1_id":"25898","arg2_id":"25899","normalized":[]},{"id":"25914","type":"CID","arg1_id":"25898","arg2_id":"25908","normalized":[]},{"id":"25915","type":"CID","arg1_id":"25903","arg2_id":"25897","normalized":[]},{"id":"25916","type":"CID","arg1_id":"25903","arg2_id":"25899","normalized":[]},{"id":"25917","type":"CID","arg1_id":"25903","arg2_id":"25908","normalized":[]},{"id":"25918","type":"CID","arg1_id":"25907","arg2_id":"25897","normalized":[]},{"id":"25919","type":"CID","arg1_id":"25907","arg2_id":"25899","normalized":[]},{"id":"25920","type":"CID","arg1_id":"25907","arg2_id":"25908","normalized":[]}]}
{"id":"25921","document_id":"12091028","passages":[{"id":"25922","type":"title","text":["Ketamine in war\/tropical surgery (a final tribute to the racemic mixture)."],"offsets":[[0,74]]},{"id":"25923","type":"abstract","text":["A technique of continuous intravenous anaesthesia with ketamine was used successfully during the Somalia civil war in 1994 and in north Uganda in 1999 for 64 operations in 62 patients, aged from 6 weeks to 70 years, undergoing limb and abdominal surgery including caesarian sections and interventions in neonates. Operations lasting up to 2h could be performed in the absence of sophisticated equipment such as pulse oximeters or ventilators in patients on spontaneous ventilation breathing air\/oxygen only. After premedication with diazepam, glycopyrrolate and local anaesthesia, and induction with standard doses of ketamine, a maintenance dose of 10-20 microg\/kg\/min of ketamine proved safe and effective. Emphasis was placed on bedside clinical monitoring, relying heavily on the heart rate. Diazepam, unless contraindicated or risky, remains the only necessary complementary drug to ketamine as it buffers its cardiovascular response and decreases the duration and intensity of operative and postoperative hallucinations. Local anaesthetic blocks were useful in decreasing the requirement for postoperative analgesia. An antisialogue was usually unnecessary in operations lasting up to 2 h, glycopyrrolate being the best choice for its lowest psychotropic and chronotropic effects, especially in a hot climate. Experience in war\/tropical settings suggests this technique could be useful in civilian contexts such as outdoor life-saving emergency surgery or in mass casualties where, e.g. amputation and rapid extrication were required."],"offsets":[[75,1615]]}],"entities":[{"id":"25924","type":"Chemical","text":["Ketamine"],"offsets":[[0,8]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"25925","type":"Chemical","text":["ketamine"],"offsets":[[130,138]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"25926","type":"Chemical","text":["oxygen"],"offsets":[[570,576]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"25927","type":"Chemical","text":["diazepam"],"offsets":[[608,616]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"25928","type":"Chemical","text":["glycopyrrolate"],"offsets":[[618,632]],"normalized":[{"db_name":"MESH","db_id":"D006024"}]},{"id":"25929","type":"Chemical","text":["ketamine"],"offsets":[[693,701]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"25930","type":"Chemical","text":["ketamine"],"offsets":[[748,756]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"25931","type":"Chemical","text":["Diazepam"],"offsets":[[871,879]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"25932","type":"Chemical","text":["ketamine"],"offsets":[[963,971]],"normalized":[{"db_name":"MESH","db_id":"D007649"}]},{"id":"25933","type":"Disease","text":["hallucinations"],"offsets":[[1086,1100]],"normalized":[{"db_name":"MESH","db_id":"D006212"}]},{"id":"25934","type":"Disease","text":["analgesia"],"offsets":[[1187,1196]],"normalized":[{"db_name":"MESH","db_id":"D000699"}]},{"id":"25935","type":"Chemical","text":["glycopyrrolate"],"offsets":[[1271,1285]],"normalized":[{"db_name":"MESH","db_id":"D006024"}]}],"events":[],"coreferences":[],"relations":[{"id":"25936","type":"CID","arg1_id":"25924","arg2_id":"25933","normalized":[]},{"id":"25937","type":"CID","arg1_id":"25925","arg2_id":"25933","normalized":[]},{"id":"25938","type":"CID","arg1_id":"25929","arg2_id":"25933","normalized":[]},{"id":"25939","type":"CID","arg1_id":"25930","arg2_id":"25933","normalized":[]},{"id":"25940","type":"CID","arg1_id":"25932","arg2_id":"25933","normalized":[]}]}
{"id":"25941","document_id":"11860495","passages":[{"id":"25942","type":"title","text":["Steroid structure and pharmacological properties determine the anti-amnesic effects of pregnenolone sulphate in the passive avoidance task in rats."],"offsets":[[0,147]]},{"id":"25943","type":"abstract","text":["Pregnenolone sulphate (PREGS) has generated interest as one of the most potent memory-enhancing neurosteroids to be examined in rodent learning studies, with particular importance in the ageing process. The mechanism by which this endogenous steroid enhances memory formation is hypothesized to involve actions on glutamatergic and GABAergic systems. This hypothesis stems from findings that PREGS is a potent positive modulator of N-methyl-d-aspartate receptors (NMDARs) and a negative modulator of gamma-aminobutyric acid(A) receptors (GABA(A)Rs). Moreover, PREGS is able to reverse the amnesic-like effects of NMDAR and GABA(A)R ligands. To investigate this hypothesis, the present study in rats examined the memory-altering abilities of structural analogs of PREGS, which differ in their modulation of NMDAR and\/or GABA(A)R function. The analogs tested were: 11-ketopregnenolone sulphate (an agent that is inactive at GABA(A)Rs and NMDARs), epipregnanolone ([3beta-hydroxy-5beta-pregnan-20-one] sulphate, an inhibitor of both GABA(A)Rs and NMDARs), and a newly synthesized (-) PREGS enantiomer (which is identical to PREGS in effects on GABA(A)Rs and NMDARs). The memory-enhancing effects of PREGS and its analogs were tested in the passive avoidance task using the model of scopolamine-induced amnesia. Both PREGS and its (-) enantiomer blocked the effects of scopolamine. The results show that, unlike PREGS, 11-ketopregnenolone sulphate and epipregnanolone sulphate failed to block the effect of scopolamine, suggesting that altering the modulation of NMDA receptors diminishes the memory-enhancing effects of PREGS. Moreover, enantioselectivity was demonstrated by the ability of natural PREGS to be an order of magnitude more effective than its synthetic enantiomer in reversing scopolamine-induced amnesia. These results identify a novel neuropharmacological site for the modulation of memory processes by neuroactive steroids."],"offsets":[[148,2085]]}],"entities":[{"id":"25944","type":"Chemical","text":["Steroid"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"25945","type":"Disease","text":["amnesic"],"offsets":[[68,75]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"25946","type":"Chemical","text":["pregnenolone sulphate"],"offsets":[[87,108]],"normalized":[{"db_name":"MESH","db_id":"C018370"}]},{"id":"25947","type":"Chemical","text":["Pregnenolone sulphate"],"offsets":[[148,169]],"normalized":[{"db_name":"MESH","db_id":"C018370"}]},{"id":"25948","type":"Chemical","text":["PREGS"],"offsets":[[171,176]],"normalized":[{"db_name":"MESH","db_id":"C018370"}]},{"id":"25949","type":"Chemical","text":["steroid"],"offsets":[[390,397]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]},{"id":"25950","type":"Chemical","text":["PREGS"],"offsets":[[540,545]],"normalized":[{"db_name":"MESH","db_id":"C018370"}]},{"id":"25951","type":"Chemical","text":["N-methyl-d-aspartate"],"offsets":[[580,600]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"25952","type":"Chemical","text":["gamma-aminobutyric acid"],"offsets":[[648,671]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"25953","type":"Chemical","text":["GABA"],"offsets":[[686,690]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"25954","type":"Chemical","text":["PREGS"],"offsets":[[708,713]],"normalized":[{"db_name":"MESH","db_id":"C018370"}]},{"id":"25955","type":"Disease","text":["amnesic"],"offsets":[[737,744]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"25956","type":"Chemical","text":["GABA"],"offsets":[[771,775]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"25957","type":"Chemical","text":["PREGS"],"offsets":[[911,916]],"normalized":[{"db_name":"MESH","db_id":"C018370"}]},{"id":"25958","type":"Chemical","text":["GABA"],"offsets":[[967,971]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"25959","type":"Chemical","text":["11-ketopregnenolone sulphate"],"offsets":[[1011,1039]],"normalized":[]},{"id":"25960","type":"Chemical","text":["GABA"],"offsets":[[1070,1074]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"25961","type":"Chemical","text":["epipregnanolone ([3beta-hydroxy-5beta-pregnan-20-one] sulphate"],"offsets":[[1093,1155]],"normalized":[{"db_name":"MESH","db_id":"C018370"}]},{"id":"25962","type":"Chemical","text":["GABA"],"offsets":[[1178,1182]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"25963","type":"Chemical","text":["PREGS"],"offsets":[[1229,1234]],"normalized":[{"db_name":"MESH","db_id":"C018370"}]},{"id":"25964","type":"Chemical","text":["PREGS"],"offsets":[[1269,1274]],"normalized":[{"db_name":"MESH","db_id":"C018370"}]},{"id":"25965","type":"Chemical","text":["GABA"],"offsets":[[1289,1293]],"normalized":[{"db_name":"MESH","db_id":"D005680"}]},{"id":"25966","type":"Chemical","text":["PREGS"],"offsets":[[1344,1349]],"normalized":[{"db_name":"MESH","db_id":"C018370"}]},{"id":"25967","type":"Chemical","text":["scopolamine"],"offsets":[[1427,1438]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"25968","type":"Disease","text":["amnesia"],"offsets":[[1447,1454]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"25969","type":"Chemical","text":["PREGS"],"offsets":[[1461,1466]],"normalized":[{"db_name":"MESH","db_id":"C018370"}]},{"id":"25970","type":"Chemical","text":["scopolamine"],"offsets":[[1513,1524]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"25971","type":"Chemical","text":["PREGS"],"offsets":[[1556,1561]],"normalized":[{"db_name":"MESH","db_id":"C018370"}]},{"id":"25972","type":"Chemical","text":["11-ketopregnenolone sulphate"],"offsets":[[1563,1591]],"normalized":[]},{"id":"25973","type":"Chemical","text":["epipregnanolone sulphate"],"offsets":[[1596,1620]],"normalized":[{"db_name":"MESH","db_id":"C018370"}]},{"id":"25974","type":"Chemical","text":["scopolamine"],"offsets":[[1651,1662]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"25975","type":"Chemical","text":["NMDA"],"offsets":[[1707,1711]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"25976","type":"Chemical","text":["PREGS"],"offsets":[[1765,1770]],"normalized":[{"db_name":"MESH","db_id":"C018370"}]},{"id":"25977","type":"Chemical","text":["PREGS"],"offsets":[[1844,1849]],"normalized":[{"db_name":"MESH","db_id":"C018370"}]},{"id":"25978","type":"Chemical","text":["scopolamine"],"offsets":[[1936,1947]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"25979","type":"Disease","text":["amnesia"],"offsets":[[1956,1963]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"25980","type":"Chemical","text":["steroids"],"offsets":[[2076,2084]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]}],"events":[],"coreferences":[],"relations":[{"id":"25981","type":"CID","arg1_id":"25967","arg2_id":"25945","normalized":[]},{"id":"25982","type":"CID","arg1_id":"25967","arg2_id":"25955","normalized":[]},{"id":"25983","type":"CID","arg1_id":"25967","arg2_id":"25968","normalized":[]},{"id":"25984","type":"CID","arg1_id":"25967","arg2_id":"25979","normalized":[]},{"id":"25985","type":"CID","arg1_id":"25970","arg2_id":"25945","normalized":[]},{"id":"25986","type":"CID","arg1_id":"25970","arg2_id":"25955","normalized":[]},{"id":"25987","type":"CID","arg1_id":"25970","arg2_id":"25968","normalized":[]},{"id":"25988","type":"CID","arg1_id":"25970","arg2_id":"25979","normalized":[]},{"id":"25989","type":"CID","arg1_id":"25974","arg2_id":"25945","normalized":[]},{"id":"25990","type":"CID","arg1_id":"25974","arg2_id":"25955","normalized":[]},{"id":"25991","type":"CID","arg1_id":"25974","arg2_id":"25968","normalized":[]},{"id":"25992","type":"CID","arg1_id":"25974","arg2_id":"25979","normalized":[]},{"id":"25993","type":"CID","arg1_id":"25978","arg2_id":"25945","normalized":[]},{"id":"25994","type":"CID","arg1_id":"25978","arg2_id":"25955","normalized":[]},{"id":"25995","type":"CID","arg1_id":"25978","arg2_id":"25968","normalized":[]},{"id":"25996","type":"CID","arg1_id":"25978","arg2_id":"25979","normalized":[]}]}
{"id":"25997","document_id":"11752998","passages":[{"id":"25998","type":"title","text":["Preliminary efficacy assessment of intrathecal injection of an American formulation of adenosine in humans."],"offsets":[[0,107]]},{"id":"25999","type":"abstract","text":["BACKGROUND: Preclinical studies of intrathecal adenosine suggest it may be effective in the treatment of acute and chronic pain in humans, and preliminary studies in volunteers and patients with a Swedish formulation of adenosine suggests it may be effective in hypersensitivity states but not with acute noxious stimulation. The purpose of this study was to screen for efficacy of a different formulation of adenosine marketed in the US, using both acute noxious stimulation and capsaicin-evoked mechanical hypersensitivity. METHODS: Following Food and Drug Administration and institutional review board approval and written informed consent, 65 volunteers were studied in two trials: an open-label, dose-escalating trial with intrathecal adenosine doses of 0.25-2.0 mg and a double-blind, placebo-controlled trial of adenosine, 2 mg. Cerebrospinal fluid was obtained for pharmacokinetic analysis, and pain ratings in response to acute heat stimuli and areas of mechanical hyperalgesia and allodynia after intradermal capsaicin injection were determined. RESULTS: Adenosine produced no effect on pain report to acute noxious thermal or chemical stimulation but reduced mechanical hyperalgesia and allodynia from intradermal capsaicin injection for at least 24 h. In contrast, residence time of adenosine in cerebrospinal fluid was short (< 4 h). CONCLUSIONS: These results show selective inhibition by intrathecal adenosine of hypersensitivity, presumed to reflect central sensitization in humans after peripheral capsaicin injection. The long-lasting effect is consistent with that observed in preliminary reports of patients with chronic neuropathic pain and is not due to prolonged residence of adenosine in cerebrospinal fluid."],"offsets":[[108,1840]]}],"entities":[{"id":"26000","type":"Chemical","text":["adenosine"],"offsets":[[87,96]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"26001","type":"Chemical","text":["adenosine"],"offsets":[[155,164]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"26002","type":"Disease","text":["acute and chronic pain"],"offsets":[[213,235]],"normalized":[{"db_name":"MESH","db_id":"D059787"},{"db_name":"MESH","db_id":"D059350"}]},{"id":"26003","type":"Disease","text":["acute","pain"],"offsets":[[213,218],[231,235]],"normalized":[{"db_name":"MESH","db_id":"D059787"}]},{"id":"26004","type":"Disease","text":["chronic pain"],"offsets":[[223,235]],"normalized":[{"db_name":"MESH","db_id":"D059350"}]},{"id":"26005","type":"Chemical","text":["adenosine"],"offsets":[[328,337]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"26006","type":"Disease","text":["hypersensitivity"],"offsets":[[370,386]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"26007","type":"Chemical","text":["adenosine"],"offsets":[[517,526]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"26008","type":"Chemical","text":["capsaicin"],"offsets":[[588,597]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"26009","type":"Disease","text":["hypersensitivity"],"offsets":[[616,632]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"26010","type":"Chemical","text":["adenosine"],"offsets":[[848,857]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"26011","type":"Chemical","text":["adenosine"],"offsets":[[927,936]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"26012","type":"Disease","text":["pain"],"offsets":[[1011,1015]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"26013","type":"Disease","text":["mechanical hyperalgesia"],"offsets":[[1071,1094]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"26014","type":"Disease","text":["allodynia"],"offsets":[[1099,1108]],"normalized":[{"db_name":"MESH","db_id":"D006930"}]},{"id":"26015","type":"Chemical","text":["capsaicin"],"offsets":[[1127,1136]],"normalized":[{"db_name":"MESH","db_id":"D002211"}]},{"id":"26016","type":"Chemical","text":["Adenosine"],"offsets":[[1173,1182]],"normalized":[{"db_name":"MESH","db_id":"D000241"}]},{"id":"26017","type":"Disease","text":["pain"],"offsets":[[1205,1209]],"normalized":[{"db_name":"MESH","db_id":"D010146"}]},{"id":"26018","type":"Disease","text":["mechanical 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{"id":"26043","document_id":"10354657","passages":[{"id":"26044","type":"title","text":["Effect of lithium maintenance therapy on thyroid and parathyroid function."],"offsets":[[0,74]]},{"id":"26045","type":"abstract","text":["OBJECTIVES: To assess changes induced by lithium maintenance therapy on the incidence of thyroid, parathyroid and ion alterations. These were evaluated with respect to the duration of lithium therapy, age, sex, and family history (whether or not the patient had a first-degree relative with thyroid disease). DESIGN: Prospective study. SETTING: Affective Disorders Clinic at St. Mary's Hospital, Montreal. PATIENTS: One hundred and one patients (28 men and 73 women) with bipolar disorder receiving lithium maintenance therapy ranging from 1 year's to 32 years' duration. The control group consisted of 82 patients with no psychiatric or endocrinological diagnoses from the hospital's out-patient clinics. OUTCOME MEASURES: Laboratory analyses of calcium, magnesium and thyroid-stimulating hormone levels performed before beginning lithium therapy and at biannual follow-up. RESULTS: Hypothyroidism developed in 40 patients, excluding 8 patients who were hypothyroid at baseline. All patients having first-degree relatives affected by thyroid illness had accelerated onset of hypothyroidism (3.7 years after onset of lithium therapy) compared with patients without a family history (8.6 years after onset of lithium therapy). Women over 60 years of age were more often affected by hypothyroidism than women under 60 years of age (34.6% versus 31.9%). Magnesium levels in patients on lithium treatment were unchanged from baseline levels. After lithium treatment, calcium levels were higher than either baseline levels or control levels. Thus, lithium treatment counteracted the decrease in plasma calcium levels associated with aging. CONCLUSIONS: Familial thyroid illness is a risk factor for hypothyroidism and hypercalcemia during lithium therapy."],"offsets":[[75,1825]]}],"entities":[{"id":"26046","type":"Chemical","text":["lithium"],"offsets":[[10,17]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"26047","type":"Chemical","text":["lithium"],"offsets":[[116,123]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"26048","type":"Chemical","text":["lithium"],"offsets":[[259,266]],"normalized":[{"db_name":"MESH","db_id":"D008094"}]},{"id":"26049","type":"Disease","text":["thyroid disease"],"offsets":[[366,381]],"normalized":[{"db_name":"MESH","db_id":"D013959"}]},{"id":"26050","type":"Disease","text":["bipolar 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{"id":"26128","document_id":"10328196","passages":[{"id":"26129","type":"title","text":["Systemic toxicity following administration of sirolimus (formerly rapamycin) for psoriasis: association of capillary leak syndrome with apoptosis of lesional lymphocytes."],"offsets":[[0,170]]},{"id":"26130","type":"abstract","text":["BACKGROUND: Sirolimus (formerly rapamycin) is an immunosuppressive agent that interferes with T-cell activation. After 2 individuals with psoriasis developed a capillary leak syndrome following treatment with oral sirolimus lesional skin cells and activated peripheral blood cells were analyzed for induction of apoptosis. OBSERVATIONS: A keratome skin specimen from 1 patient with sirolimus-induced capillary leak syndrome had a 2.3-fold increase in percentage of apoptotic cells (to 48%) compared with an unaffected sirolimus-treated patient with psoriasis (21%). Activated peripheral blood T cells from patients with psoriasis tended to exhibit greater spontaneous or dexamethasone-induced apoptosis than did normal T cells, particularly in the presence of sirolimus. CONCLUSIONS: Severe adverse effects of sirolimus include fever, anemia, and capillary leak syndrome. These symptoms may be the result of drug-induced apoptosis of lesional leukocytes, especially activated T lymphocytes, and possibly release of inflammatory mediators. Because patients with severe psoriasis may develop capillary leak from various systemic therapies, clinical monitoring is advisable for patients with inflammatory diseases who are treated with immune modulators."],"offsets":[[171,1421]]}],"entities":[{"id":"26131","type":"Disease","text":["toxicity"],"offsets":[[9,17]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"26132","type":"Chemical","text":["sirolimus"],"offsets":[[46,55]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"26133","type":"Chemical","text":["rapamycin"],"offsets":[[66,75]],"normalized":[{"db_name":"MESH","db_id":"D020123"}]},{"id":"26134","type":"Disease","text":["psoriasis"],"offsets":[[81,90]],"normalized":[{"db_name":"MESH","db_id":"D011565"}]},{"id":"26135","type":"Disease","text":["capillary leak 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leak syndrome"],"offsets":[[1018,1041]],"normalized":[{"db_name":"MESH","db_id":"D019559"}]},{"id":"26152","type":"Disease","text":["psoriasis"],"offsets":[[1239,1248]],"normalized":[{"db_name":"MESH","db_id":"D011565"}]},{"id":"26153","type":"Disease","text":["capillary leak"],"offsets":[[1261,1275]],"normalized":[{"db_name":"MESH","db_id":"D019559"}]},{"id":"26154","type":"Disease","text":["inflammatory diseases"],"offsets":[[1360,1381]],"normalized":[{"db_name":"MESH","db_id":"D007249"}]}],"events":[],"coreferences":[],"relations":[{"id":"26155","type":"CID","arg1_id":"26132","arg2_id":"26135","normalized":[]},{"id":"26156","type":"CID","arg1_id":"26132","arg2_id":"26139","normalized":[]},{"id":"26157","type":"CID","arg1_id":"26132","arg2_id":"26142","normalized":[]},{"id":"26158","type":"CID","arg1_id":"26132","arg2_id":"26151","normalized":[]},{"id":"26159","type":"CID","arg1_id":"26132","arg2_id":"26153","normalized":[]},{"id":"26160","type":"CID","arg1_id":"26133","arg2_id":"26135","normalized":[]},{"id":"26161","type":"CID","arg1_id":"26133","arg2_id":"26139","normalized":[]},{"id":"26162","type":"CID","arg1_id":"26133","arg2_id":"26142","normalized":[]},{"id":"26163","type":"CID","arg1_id":"26133","arg2_id":"26151","normalized":[]},{"id":"26164","type":"CID","arg1_id":"26133","arg2_id":"26153","normalized":[]},{"id":"26165","type":"CID","arg1_id":"26136","arg2_id":"26135","normalized":[]},{"id":"26166","type":"CID","arg1_id":"26136","arg2_id":"26139","normalized":[]},{"id":"26167","type":"CID","arg1_id":"26136","arg2_id":"26142","normalized":[]},{"id":"26168","type":"CID","arg1_id":"26136","arg2_id":"26151","normalized":[]},{"id":"26169","type":"CID","arg1_id":"26136","arg2_id":"26153","normalized":[]},{"id":"26170","type":"CID","arg1_id":"26137","arg2_id":"26135","normalized":[]},{"id":"26171","type":"CID","arg1_id":"26137","arg2_id":"26139","normalized":[]},{"id":"26172","type":"CID","arg1_id":"26137","arg2_id":"26142","normalized":[]},{"id":"26173","type":"CID","arg1_id":"26137","arg2_id":"26151","normalized":[]},{"id":"26174","type":"CID","arg1_id":"26137","arg2_id":"26153","normalized":[]},{"id":"26175","type":"CID","arg1_id":"26140","arg2_id":"26135","normalized":[]},{"id":"26176","type":"CID","arg1_id":"26140","arg2_id":"26139","normalized":[]},{"id":"26177","type":"CID","arg1_id":"26140","arg2_id":"26142","normalized":[]},{"id":"26178","type":"CID","arg1_id":"26140","arg2_id":"26151","normalized":[]},{"id":"26179","type":"CID","arg1_id":"26140","arg2_id":"26153","normalized":[]},{"id":"26180","type":"CID","arg1_id":"26141","arg2_id":"26135","normalized":[]},{"id":"26181","type":"CID","arg1_id":"26141","arg2_id":"26139","normalized":[]},{"id":"26182","type":"CID","arg1_id":"26141","arg2_id":"26142","normalized":[]},{"id":"26183","type":"CID","arg1_id":"26141","arg2_id":"26151","normalized":[]},{"id":"26184","type":"CID","arg1_id":"26141","arg2_id":"26153","normalized":[]},{"id":"26185","type":"CID","arg1_id":"26143","arg2_id":"26135","normalized":[]},{"id":"26186","type":"CID","arg1_id":"26143","arg2_id":"26139","normalized":[]},{"id":"26187","type":"CID","arg1_id":"26143","arg2_id":"26142","normalized":[]},{"id":"26188","type":"CID","arg1_id":"26143","arg2_id":"26151","normalized":[]},{"id":"26189","type":"CID","arg1_id":"26143","arg2_id":"26153","normalized":[]},{"id":"26190","type":"CID","arg1_id":"26147","arg2_id":"26135","normalized":[]},{"id":"26191","type":"CID","arg1_id":"26147","arg2_id":"26139","normalized":[]},{"id":"26192","type":"CID","arg1_id":"26147","arg2_id":"26142","normalized":[]},{"id":"26193","type":"CID","arg1_id":"26147","arg2_id":"26151","normalized":[]},{"id":"26194","type":"CID","arg1_id":"26147","arg2_id":"26153","normalized":[]},{"id":"26195","type":"CID","arg1_id":"26148","arg2_id":"26135","normalized":[]},{"id":"26196","type":"CID","arg1_id":"26148","arg2_id":"26139","normalized":[]},{"id":"26197","type":"CID","arg1_id":"26148","arg2_id":"26142","normalized":[]},{"id":"26198","type":"CID","arg1_id":"26148","arg2_id":"26151","normalized":[]},{"id":"26199","type":"CID","arg1_id":"26148","arg2_id":"26153","normalized":[]}]}
{"id":"26200","document_id":"9630698","passages":[{"id":"26201","type":"title","text":["Contribution of the glycine site of NMDA receptors in rostral and intermediate-caudal parts of the striatum to the regulation of muscle tone in rats."],"offsets":[[0,149]]},{"id":"26202","type":"abstract","text":["The aim of the present study was to assess the contribution of the glycine site of NMDA receptors in the striatum to the regulation of muscle tone. Muscle tone was examined using a combined mechanoand electromyographic method, which measured simultaneously the muscle resistance (MMG) of the rat's hind foot to passive extension and flexion in the ankle joint and the electromyographic activity (EMG) of the antagonistic muscles of that joint: gastrocnemius and tibialis anterior. Muscle rigidity was induced by haloperidol (2.5 mg\/kg i.p.). 5,7-dichlorokynurenic acid (5,7-DCKA), a selective glycine site antagonist, injected in doses of 2.5 and 4.5 microg\/0.5 microl bilaterally, into the rostral region of the striatum, decreased both the haloperidol-induced muscle rigidity (MMG) and the enhanced electromyographic activity (EMG). 5,7-DCKA injected bilaterally in a dose of 4.5 microg\/0.5 microl into the intermediate-caudal region of the striatum of rats not pretreated with haloperidol had no effect on the muscle tone. The present results suggest that blockade of the glycine site of NMDA receptors in the rostral part of the striatum may be mainly responsible for the antiparkinsonian action of this drug."],"offsets":[[150,1363]]}],"entities":[{"id":"26203","type":"Chemical","text":["glycine"],"offsets":[[20,27]],"normalized":[{"db_name":"MESH","db_id":"D005998"}]},{"id":"26204","type":"Chemical","text":["NMDA"],"offsets":[[36,40]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"26205","type":"Chemical","text":["glycine"],"offsets":[[217,224]],"normalized":[{"db_name":"MESH","db_id":"D005998"}]},{"id":"26206","type":"Chemical","text":["NMDA"],"offsets":[[233,237]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]},{"id":"26207","type":"Disease","text":["Muscle rigidity"],"offsets":[[631,646]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"26208","type":"Chemical","text":["haloperidol"],"offsets":[[662,673]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"26209","type":"Chemical","text":["5,7-dichlorokynurenic acid"],"offsets":[[692,718]],"normalized":[{"db_name":"MESH","db_id":"C066192"}]},{"id":"26210","type":"Chemical","text":["5,7-DCKA"],"offsets":[[720,728]],"normalized":[{"db_name":"MESH","db_id":"C066192"}]},{"id":"26211","type":"Chemical","text":["glycine"],"offsets":[[743,750]],"normalized":[{"db_name":"MESH","db_id":"D005998"}]},{"id":"26212","type":"Chemical","text":["haloperidol"],"offsets":[[892,903]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"26213","type":"Disease","text":["muscle rigidity"],"offsets":[[912,927]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"26214","type":"Chemical","text":["5,7-DCKA"],"offsets":[[985,993]],"normalized":[{"db_name":"MESH","db_id":"C066192"}]},{"id":"26215","type":"Chemical","text":["haloperidol"],"offsets":[[1130,1141]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"26216","type":"Chemical","text":["glycine"],"offsets":[[1225,1232]],"normalized":[{"db_name":"MESH","db_id":"D005998"}]},{"id":"26217","type":"Chemical","text":["NMDA"],"offsets":[[1241,1245]],"normalized":[{"db_name":"MESH","db_id":"D016202"}]}],"events":[],"coreferences":[],"relations":[{"id":"26218","type":"CID","arg1_id":"26208","arg2_id":"26207","normalized":[]},{"id":"26219","type":"CID","arg1_id":"26208","arg2_id":"26213","normalized":[]},{"id":"26220","type":"CID","arg1_id":"26212","arg2_id":"26207","normalized":[]},{"id":"26221","type":"CID","arg1_id":"26212","arg2_id":"26213","normalized":[]},{"id":"26222","type":"CID","arg1_id":"26215","arg2_id":"26207","normalized":[]},{"id":"26223","type":"CID","arg1_id":"26215","arg2_id":"26213","normalized":[]}]}
{"id":"26224","document_id":"8480959","passages":[{"id":"26225","type":"title","text":["Efficacy and tolerability of lovastatin in 3390 women with moderate hypercholesterolemia."],"offsets":[[0,89]]},{"id":"26226","type":"abstract","text":["OBJECTIVE: To evaluate the efficacy and safety of lovastatin in women with moderate hypercholesterolemia. DESIGN: The Expanded Clinical Evaluation of Lovastatin (EXCEL) Study, a multicenter, double-blind, diet- and placebo-controlled trial, in which participants were randomly assigned to receive placebo or lovastatin at doses of 20 or 40 mg once daily, or 20 or 40 mg twice daily for 48 weeks. SETTING: Ambulatory patients recruited by 362 participating centers throughout the United States. PATIENTS: Women (n = 3390) from the total cohort of 8245 volunteers. MEASUREMENTS: Plasma total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, and triglycerides; and laboratory and clinical evidence of adverse events monitored periodically throughout the study. RESULTS: Among women, lovastatin (20 to 80 mg\/d) produced sustained (12- to 48-week), dose-related changes (P < 0.001): decreases in LDL cholesterol (24% to 40%) and triglycerides (9% to 18%), and increases in HDL cholesterol (6.7% to 8.6%). Depending on the dose, from 82% to 95% of lovastatin-treated women achieved the National Cholesterol Education Program goal of LDL cholesterol levels less than 4.14 mmol\/L (160 mg\/dL), and 40% to 87% achieved the goal of 3.36 mmol\/L (130 mg\/dL). Successive transaminase elevations greater than three times the upper limit of normal occurred in 0.1% of women and were dose dependent above the 20-mg dose. Myopathy, defined as muscle symptoms with creatine kinase elevations greater than 10 times the upper limit of normal, was rare and associated with the highest recommended daily dose of lovastatin (80 mg). Estrogen-replacement therapy appeared to have no effect on either the efficacy or safety profile of lovastatin. CONCLUSION: Lovastatin is highly effective and generally well tolerated as therapy for primary hypercholesterolemia in women."],"offsets":[[90,1967]]}],"entities":[{"id":"26227","type":"Chemical","text":["lovastatin"],"offsets":[[29,39]],"normalized":[{"db_name":"MESH","db_id":"D008148"}]},{"id":"26228","type":"Disease","text":["hypercholesterolemia"],"offsets":[[68,88]],"normalized":[{"db_name":"MESH","db_id":"D006937"}]},{"id":"26229","type":"Chemical","text":["lovastatin"],"offsets":[[140,150]],"normalized":[{"db_name":"MESH","db_id":"D008148"}]},{"id":"26230","type":"Disease","text":["hypercholesterolemia"],"offsets":[[174,194]],"normalized":[{"db_name":"MESH","db_id":"D006937"}]},{"id":"26231","type":"Chemical","text":["Lovastatin"],"offsets":[[240,250]],"normalized":[{"db_name":"MESH","db_id":"D008148"}]},{"id":"26232","type":"Chemical","text":["lovastatin"],"offsets":[[398,408]],"normalized":[{"db_name":"MESH","db_id":"D008148"}]},{"id":"26233","type":"Chemical","text":["cholesterol"],"offsets":[[747,758]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"26234","type":"Chemical","text":["triglycerides"],"offsets":[[764,777]],"normalized":[{"db_name":"MESH","db_id":"D014280"}]},{"id":"26235","type":"Chemical","text":["lovastatin"],"offsets":[[901,911]],"normalized":[{"db_name":"MESH","db_id":"D008148"}]},{"id":"26236","type":"Chemical","text":["cholesterol"],"offsets":[[1016,1027]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"26237","type":"Chemical","text":["triglycerides"],"offsets":[[1045,1058]],"normalized":[{"db_name":"MESH","db_id":"D014280"}]},{"id":"26238","type":"Chemical","text":["cholesterol"],"offsets":[[1093,1104]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"26239","type":"Chemical","text":["lovastatin"],"offsets":[[1163,1173]],"normalized":[{"db_name":"MESH","db_id":"D008148"}]},{"id":"26240","type":"Chemical","text":["Cholesterol"],"offsets":[[1210,1221]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"26241","type":"Chemical","text":["cholesterol"],"offsets":[[1252,1263]],"normalized":[{"db_name":"MESH","db_id":"D002784"}]},{"id":"26242","type":"Disease","text":["Myopathy"],"offsets":[[1525,1533]],"normalized":[{"db_name":"MESH","db_id":"D009135"}]},{"id":"26243","type":"Chemical","text":["creatine"],"offsets":[[1567,1575]],"normalized":[{"db_name":"MESH","db_id":"D003401"}]},{"id":"26244","type":"Chemical","text":["lovastatin"],"offsets":[[1710,1720]],"normalized":[{"db_name":"MESH","db_id":"D008148"}]},{"id":"26245","type":"Chemical","text":["lovastatin"],"offsets":[[1830,1840]],"normalized":[{"db_name":"MESH","db_id":"D008148"}]},{"id":"26246","type":"Chemical","text":["Lovastatin"],"offsets":[[1854,1864]],"normalized":[{"db_name":"MESH","db_id":"D008148"}]},{"id":"26247","type":"Disease","text":["hypercholesterolemia"],"offsets":[[1937,1957]],"normalized":[{"db_name":"MESH","db_id":"D006937"}]}],"events":[],"coreferences":[],"relations":[{"id":"26248","type":"CID","arg1_id":"26227","arg2_id":"26242","normalized":[]},{"id":"26249","type":"CID","arg1_id":"26229","arg2_id":"26242","normalized":[]},{"id":"26250","type":"CID","arg1_id":"26231","arg2_id":"26242","normalized":[]},{"id":"26251","type":"CID","arg1_id":"26232","arg2_id":"26242","normalized":[]},{"id":"26252","type":"CID","arg1_id":"26235","arg2_id":"26242","normalized":[]},{"id":"26253","type":"CID","arg1_id":"26239","arg2_id":"26242","normalized":[]},{"id":"26254","type":"CID","arg1_id":"26244","arg2_id":"26242","normalized":[]},{"id":"26255","type":"CID","arg1_id":"26245","arg2_id":"26242","normalized":[]},{"id":"26256","type":"CID","arg1_id":"26246","arg2_id":"26242","normalized":[]}]}
{"id":"26257","document_id":"7197363","passages":[{"id":"26258","type":"title","text":["REM sleep deprivation changes behavioral response to catecholaminergic and serotonergic receptor activation in rats."],"offsets":[[0,116]]},{"id":"26259","type":"abstract","text":["The effects of REM sleep deprivation (REMD) on apomorphine-induced aggressiveness and quipazine-induced head twitches in rats were determined. Forty-eight hr of REMD increased apomorphine-induced aggressiveness, and reduced (immediately after completing of REMD) or increased (96 hr after completing of REMD) quipazine-induced head twitches. Results are discussed in terms of similarity to pharmacological effects of other antidepressive treatments."],"offsets":[[117,566]]}],"entities":[{"id":"26260","type":"Disease","text":["REM sleep deprivation"],"offsets":[[0,21]],"normalized":[{"db_name":"MESH","db_id":"D012892"}]},{"id":"26261","type":"Disease","text":["REM sleep deprivation"],"offsets":[[132,153]],"normalized":[{"db_name":"MESH","db_id":"D012892"}]},{"id":"26262","type":"Disease","text":["REMD"],"offsets":[[155,159]],"normalized":[{"db_name":"MESH","db_id":"D012892"}]},{"id":"26263","type":"Chemical","text":["apomorphine"],"offsets":[[164,175]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"26264","type":"Disease","text":["aggressiveness"],"offsets":[[184,198]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"26265","type":"Chemical","text":["quipazine"],"offsets":[[203,212]],"normalized":[{"db_name":"MESH","db_id":"D011814"}]},{"id":"26266","type":"Disease","text":["head twitches"],"offsets":[[221,234]],"normalized":[{"db_name":"MESH","db_id":"D009069"}]},{"id":"26267","type":"Disease","text":["REMD"],"offsets":[[278,282]],"normalized":[{"db_name":"MESH","db_id":"D012892"}]},{"id":"26268","type":"Chemical","text":["apomorphine"],"offsets":[[293,304]],"normalized":[{"db_name":"MESH","db_id":"D001058"}]},{"id":"26269","type":"Disease","text":["aggressiveness"],"offsets":[[313,327]],"normalized":[{"db_name":"MESH","db_id":"D001523"}]},{"id":"26270","type":"Disease","text":["REMD"],"offsets":[[374,378]],"normalized":[{"db_name":"MESH","db_id":"D012892"}]},{"id":"26271","type":"Disease","text":["REMD"],"offsets":[[420,424]],"normalized":[{"db_name":"MESH","db_id":"D012892"}]},{"id":"26272","type":"Chemical","text":["quipazine"],"offsets":[[426,435]],"normalized":[{"db_name":"MESH","db_id":"D011814"}]},{"id":"26273","type":"Disease","text":["head twitches"],"offsets":[[444,457]],"normalized":[{"db_name":"MESH","db_id":"D009069"}]}],"events":[],"coreferences":[],"relations":[{"id":"26274","type":"CID","arg1_id":"26265","arg2_id":"26266","normalized":[]},{"id":"26275","type":"CID","arg1_id":"26265","arg2_id":"26273","normalized":[]},{"id":"26276","type":"CID","arg1_id":"26272","arg2_id":"26266","normalized":[]},{"id":"26277","type":"CID","arg1_id":"26272","arg2_id":"26273","normalized":[]},{"id":"26278","type":"CID","arg1_id":"26263","arg2_id":"26264","normalized":[]},{"id":"26279","type":"CID","arg1_id":"26263","arg2_id":"26269","normalized":[]},{"id":"26280","type":"CID","arg1_id":"26268","arg2_id":"26264","normalized":[]},{"id":"26281","type":"CID","arg1_id":"26268","arg2_id":"26269","normalized":[]}]}
{"id":"26282","document_id":"7161250","passages":[{"id":"26283","type":"title","text":["Extrapyramidal side effects and oral haloperidol: an analysis of explanatory patient and treatment characteristics."],"offsets":[[0,115]]},{"id":"26284","type":"abstract","text":["The incidence of extrapyramidal side effects (EPS) was evaluated in 98 patients treated with haloperidol. The incidence of parkinsonism was higher at higher doses of haloperidol and in younger patients. Prophylactic antiparkinsonian medication was effective in younger but not in older patients. However, these medications were more effective in both young and old patients when given after parkinsonism developed. Akathisia was controlled by the benzodiazepine lorazepam in 14 out of 16 patients, while prophylactic antiparkinsonians were ineffective. The present study points to patient characteristics that may be of significance in the development of EPS due to haloperidol."],"offsets":[[116,794]]}],"entities":[{"id":"26285","type":"Chemical","text":["haloperidol"],"offsets":[[37,48]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"26286","type":"Chemical","text":["haloperidol"],"offsets":[[209,220]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"26287","type":"Disease","text":["parkinsonism"],"offsets":[[239,251]],"normalized":[{"db_name":"MESH","db_id":"D010302"}]},{"id":"26288","type":"Chemical","text":["haloperidol"],"offsets":[[282,293]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"26289","type":"Disease","text":["parkinsonism"],"offsets":[[507,519]],"normalized":[{"db_name":"MESH","db_id":"D010302"}]},{"id":"26290","type":"Disease","text":["Akathisia"],"offsets":[[531,540]],"normalized":[{"db_name":"MESH","db_id":"D017109"}]},{"id":"26291","type":"Chemical","text":["benzodiazepine"],"offsets":[[563,577]],"normalized":[{"db_name":"MESH","db_id":"D001569"}]},{"id":"26292","type":"Chemical","text":["lorazepam"],"offsets":[[578,587]],"normalized":[{"db_name":"MESH","db_id":"D008140"}]},{"id":"26293","type":"Chemical","text":["haloperidol"],"offsets":[[782,793]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]}],"events":[],"coreferences":[],"relations":[{"id":"26294","type":"CID","arg1_id":"26285","arg2_id":"26287","normalized":[]},{"id":"26295","type":"CID","arg1_id":"26285","arg2_id":"26289","normalized":[]},{"id":"26296","type":"CID","arg1_id":"26286","arg2_id":"26287","normalized":[]},{"id":"26297","type":"CID","arg1_id":"26286","arg2_id":"26289","normalized":[]},{"id":"26298","type":"CID","arg1_id":"26288","arg2_id":"26287","normalized":[]},{"id":"26299","type":"CID","arg1_id":"26288","arg2_id":"26289","normalized":[]},{"id":"26300","type":"CID","arg1_id":"26293","arg2_id":"26287","normalized":[]},{"id":"26301","type":"CID","arg1_id":"26293","arg2_id":"26289","normalized":[]}]}
{"id":"26302","document_id":"7053705","passages":[{"id":"26303","type":"title","text":["Hepatic veno-occlusive disease caused by 6-thioguanine."],"offsets":[[0,55]]},{"id":"26304","type":"abstract","text":["Clinically reversible veno-occlusive disease of the liver developed in a 23-year-old man with acute lymphocytic leukemia after 10 months of maintenance therapy with 6-thioguanine. Serial liver biopsies showed the development and resolution of intense sinusoidal engorgement. Although this disease was clinically reversible, some subintimal fibrosis about the terminal hepatic veins persisted. This case presented a unique opportunity to observe the histologic features of clinically reversible hepatic veno-occlusive disease over time, and may be the first case of veno-occlusive related solely to 6-thioguanine."],"offsets":[[56,668]]}],"entities":[{"id":"26305","type":"Disease","text":["Hepatic veno-occlusive disease"],"offsets":[[0,30]],"normalized":[{"db_name":"MESH","db_id":"D006504"}]},{"id":"26306","type":"Chemical","text":["6-thioguanine"],"offsets":[[41,54]],"normalized":[{"db_name":"MESH","db_id":"D013866"}]},{"id":"26307","type":"Disease","text":["veno-occlusive disease of the liver"],"offsets":[[78,113]],"normalized":[{"db_name":"MESH","db_id":"D006504"}]},{"id":"26308","type":"Disease","text":["acute lymphocytic leukemia"],"offsets":[[150,176]],"normalized":[{"db_name":"MESH","db_id":"D054198"}]},{"id":"26309","type":"Chemical","text":["6-thioguanine"],"offsets":[[221,234]],"normalized":[{"db_name":"MESH","db_id":"D013866"}]},{"id":"26310","type":"Disease","text":["fibrosis"],"offsets":[[396,404]],"normalized":[{"db_name":"MESH","db_id":"D005355"}]},{"id":"26311","type":"Disease","text":["hepatic veno-occlusive disease"],"offsets":[[550,580]],"normalized":[{"db_name":"MESH","db_id":"D006504"}]},{"id":"26312","type":"Chemical","text":["6-thioguanine"],"offsets":[[654,667]],"normalized":[{"db_name":"MESH","db_id":"D013866"}]}],"events":[],"coreferences":[],"relations":[{"id":"26313","type":"CID","arg1_id":"26306","arg2_id":"26305","normalized":[]},{"id":"26314","type":"CID","arg1_id":"26306","arg2_id":"26307","normalized":[]},{"id":"26315","type":"CID","arg1_id":"26306","arg2_id":"26311","normalized":[]},{"id":"26316","type":"CID","arg1_id":"26309","arg2_id":"26305","normalized":[]},{"id":"26317","type":"CID","arg1_id":"26309","arg2_id":"26307","normalized":[]},{"id":"26318","type":"CID","arg1_id":"26309","arg2_id":"26311","normalized":[]},{"id":"26319","type":"CID","arg1_id":"26312","arg2_id":"26305","normalized":[]},{"id":"26320","type":"CID","arg1_id":"26312","arg2_id":"26307","normalized":[]},{"id":"26321","type":"CID","arg1_id":"26312","arg2_id":"26311","normalized":[]}]}
{"id":"26322","document_id":"6402369","passages":[{"id":"26323","type":"title","text":["Treatment of ifosfamide-induced urothelial toxicity by oral administration of sodium 2-mercaptoethane sulphonate (MESNA) to patients with inoperable lung cancer."],"offsets":[[0,161]]},{"id":"26324","type":"abstract","text":["The protective effect of oral administration of the thiol compound sodium 2-mercaptoethane sulphonate (MESNA) against urothelial toxicity induced by ifosfamide (IF) was tested in a group of 45 patients with inoperable lung cancer under treatment with IF (2250 mg\/m2 on days 2-5) as part of a polychemotherapy regimen repeated in a 4-week cycle. MESNA was given orally on the days of treatment with IF in 3 doses of 840 mg\/m2, each administered at 0 hr (= injection of IF), 4 hr and 8 hr p.i. Out of a total of 88 courses of this treatment we observed 10 episodes of asymptomatic microscopic haematuria and no episodes of gross haematuria. In this group of 45 patients under protection with MESNA there were 5 complete remissions and 9 partial remissions (total 31%). A further group of 25 patients under polychemotherapy with IF were treated by conventional prophylactic measures (raised fluid intake and forced diuresis). In this group there were 1 complete and 5 partial remissions (total 24%), but nearly all patients developed either gross haematuria and\/or symptoms of bladder irritation (cystitis and pollakisuria). There were no appreciable differences between the MESNA series and the conventional prophylaxis series with respect to either haematological or systemic toxicity of the cytostatic treatment. Our results support the view that MESNA, given orally in conjunction with combined cytostatic regimens which include IF, simplifies the treatment and provides optimum protection for the urinary epithelium. Protection with oral MESNA is particularly suitable for outpatients."],"offsets":[[162,1749]]}],"entities":[{"id":"26325","type":"Chemical","text":["ifosfamide"],"offsets":[[13,23]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"26326","type":"Disease","text":["urothelial toxicity"],"offsets":[[32,51]],"normalized":[{"db_name":"MESH","db_id":"D001745"}]},{"id":"26327","type":"Chemical","text":["sodium 2-mercaptoethane sulphonate"],"offsets":[[78,112]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"26328","type":"Chemical","text":["MESNA"],"offsets":[[114,119]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"26329","type":"Disease","text":["lung cancer"],"offsets":[[149,160]],"normalized":[{"db_name":"MESH","db_id":"D008175"}]},{"id":"26330","type":"Chemical","text":["thiol"],"offsets":[[214,219]],"normalized":[{"db_name":"MESH","db_id":"D013438"}]},{"id":"26331","type":"Chemical","text":["sodium 2-mercaptoethane sulphonate"],"offsets":[[229,263]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"26332","type":"Chemical","text":["MESNA"],"offsets":[[265,270]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"26333","type":"Disease","text":["urothelial toxicity"],"offsets":[[280,299]],"normalized":[{"db_name":"MESH","db_id":"D001745"}]},{"id":"26334","type":"Chemical","text":["ifosfamide"],"offsets":[[311,321]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"26335","type":"Chemical","text":["IF"],"offsets":[[323,325]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"26336","type":"Disease","text":["lung cancer"],"offsets":[[380,391]],"normalized":[{"db_name":"MESH","db_id":"D008175"}]},{"id":"26337","type":"Chemical","text":["IF"],"offsets":[[413,415]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"26338","type":"Chemical","text":["MESNA"],"offsets":[[507,512]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"26339","type":"Chemical","text":["IF"],"offsets":[[560,562]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"26340","type":"Chemical","text":["IF"],"offsets":[[630,632]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"26341","type":"Disease","text":["haematuria"],"offsets":[[753,763]],"normalized":[{"db_name":"MESH","db_id":"D006417"}]},{"id":"26342","type":"Disease","text":["haematuria"],"offsets":[[789,799]],"normalized":[{"db_name":"MESH","db_id":"D006417"}]},{"id":"26343","type":"Chemical","text":["MESNA"],"offsets":[[852,857]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"26344","type":"Chemical","text":["IF"],"offsets":[[988,990]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"26345","type":"Disease","text":["haematuria"],"offsets":[[1206,1216]],"normalized":[{"db_name":"MESH","db_id":"D006417"}]},{"id":"26346","type":"Disease","text":["bladder irritation"],"offsets":[[1236,1254]],"normalized":[{"db_name":"MESH","db_id":"D001745"}]},{"id":"26347","type":"Disease","text":["cystitis"],"offsets":[[1256,1264]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"26348","type":"Disease","text":["pollakisuria"],"offsets":[[1269,1281]],"normalized":[{"db_name":"MESH","db_id":"D014555"}]},{"id":"26349","type":"Chemical","text":["MESNA"],"offsets":[[1334,1339]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"26350","type":"Disease","text":["toxicity"],"offsets":[[1437,1445]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"26351","type":"Chemical","text":["MESNA"],"offsets":[[1509,1514]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]},{"id":"26352","type":"Chemical","text":["IF"],"offsets":[[1592,1594]],"normalized":[{"db_name":"MESH","db_id":"D007069"}]},{"id":"26353","type":"Chemical","text":["MESNA"],"offsets":[[1702,1707]],"normalized":[{"db_name":"MESH","db_id":"D015080"}]}],"events":[],"coreferences":[],"relations":[{"id":"26354","type":"CID","arg1_id":"26325","arg2_id":"26326","normalized":[]},{"id":"26355","type":"CID","arg1_id":"26325","arg2_id":"26333","normalized":[]},{"id":"26356","type":"CID","arg1_id":"26325","arg2_id":"26346","normalized":[]},{"id":"26357","type":"CID","arg1_id":"26334","arg2_id":"26326","normalized":[]},{"id":"26358","type":"CID","arg1_id":"26334","arg2_id":"26333","normalized":[]},{"id":"26359","type":"CID","arg1_id":"26334","arg2_id":"26346","normalized":[]},{"id":"26360","type":"CID","arg1_id":"26335","arg2_id":"26326","normalized":[]},{"id":"26361","type":"CID","arg1_id":"26335","arg2_id":"26333","normalized":[]},{"id":"26362","type":"CID","arg1_id":"26335","arg2_id":"26346","normalized":[]},{"id":"26363","type":"CID","arg1_id":"26337","arg2_id":"26326","normalized":[]},{"id":"26364","type":"CID","arg1_id":"26337","arg2_id":"26333","normalized":[]},{"id":"26365","type":"CID","arg1_id":"26337","arg2_id":"26346","normalized":[]},{"id":"26366","type":"CID","arg1_id":"26339","arg2_id":"26326","normalized":[]},{"id":"26367","type":"CID","arg1_id":"26339","arg2_id":"26333","normalized":[]},{"id":"26368","type":"CID","arg1_id":"26339","arg2_id":"26346","normalized":[]},{"id":"26369","type":"CID","arg1_id":"26340","arg2_id":"26326","normalized":[]},{"id":"26370","type":"CID","arg1_id":"26340","arg2_id":"26333","normalized":[]},{"id":"26371","type":"CID","arg1_id":"26340","arg2_id":"26346","normalized":[]},{"id":"26372","type":"CID","arg1_id":"26344","arg2_id":"26326","normalized":[]},{"id":"26373","type":"CID","arg1_id":"26344","arg2_id":"26333","normalized":[]},{"id":"26374","type":"CID","arg1_id":"26344","arg2_id":"26346","normalized":[]},{"id":"26375","type":"CID","arg1_id":"26352","arg2_id":"26326","normalized":[]},{"id":"26376","type":"CID","arg1_id":"26352","arg2_id":"26333","normalized":[]},{"id":"26377","type":"CID","arg1_id":"26352","arg2_id":"26346","normalized":[]}]}
{"id":"26378","document_id":"3973521","passages":[{"id":"26379","type":"title","text":["Time course alterations of QTC interval due to hypaque 76."],"offsets":[[0,58]]},{"id":"26380","type":"abstract","text":["Sequential measurement of QT interval during left ventricular angiography was made 30 seconds and one, three, five and ten minutes after injection of hypaque 76. The subjects were ten patients found to have normal left ventricles and coronary arteries. Significant QTC prolongation occurred in 30 seconds to one minute in association with marked hypotension and elevation of cardiac output."],"offsets":[[59,449]]}],"entities":[{"id":"26381","type":"Chemical","text":["hypaque 76"],"offsets":[[47,57]],"normalized":[{"db_name":"MESH","db_id":"C027278"}]},{"id":"26382","type":"Chemical","text":["hypaque 76"],"offsets":[[209,219]],"normalized":[{"db_name":"MESH","db_id":"C027278"}]},{"id":"26383","type":"Disease","text":["QTC prolongation"],"offsets":[[324,340]],"normalized":[{"db_name":"MESH","db_id":"D008133"}]},{"id":"26384","type":"Disease","text":["hypotension"],"offsets":[[405,416]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]}],"events":[],"coreferences":[],"relations":[{"id":"26385","type":"CID","arg1_id":"26381","arg2_id":"26384","normalized":[]},{"id":"26386","type":"CID","arg1_id":"26382","arg2_id":"26384","normalized":[]},{"id":"26387","type":"CID","arg1_id":"26381","arg2_id":"26383","normalized":[]},{"id":"26388","type":"CID","arg1_id":"26382","arg2_id":"26383","normalized":[]}]}
{"id":"26389","document_id":"3461217","passages":[{"id":"26390","type":"title","text":["Production of autochthonous prostate cancer in Lobund-Wistar rats by treatments with N-nitroso-N-methylurea and testosterone."],"offsets":[[0,125]]},{"id":"26391","type":"abstract","text":["More than 50% of Lobund-Wistar (L-W) strain rats developed large, palpable prostate adenocarcinomas (PAs) following treatments with N-nitroso-N-methylurea (CAS: 684-93-5) and testosterone propionate [(TP) CAS: 57-85-2], and most of the tumor-bearing rats manifested metastatic lesions. The incubation periods averaged 10.6 months. Within the same timeframe, no L-W rat developed a similar palpable PA when treated only with TP. In L-W rats, TP acted as a tumor enhancement agent, with primary emphasis on the development of prostate cancer."],"offsets":[[126,666]]}],"entities":[{"id":"26392","type":"Disease","text":["prostate cancer"],"offsets":[[28,43]],"normalized":[{"db_name":"MESH","db_id":"D011471"}]},{"id":"26393","type":"Chemical","text":["N-nitroso-N-methylurea"],"offsets":[[85,107]],"normalized":[{"db_name":"MESH","db_id":"D008770"}]},{"id":"26394","type":"Chemical","text":["testosterone"],"offsets":[[112,124]],"normalized":[{"db_name":"MESH","db_id":"D013739"}]},{"id":"26395","type":"Disease","text":["prostate adenocarcinomas"],"offsets":[[201,225]],"normalized":[{"db_name":"MESH","db_id":"D011471"}]},{"id":"26396","type":"Disease","text":["PAs"],"offsets":[[227,230]],"normalized":[{"db_name":"MESH","db_id":"D011471"}]},{"id":"26397","type":"Chemical","text":["N-nitroso-N-methylurea"],"offsets":[[258,280]],"normalized":[{"db_name":"MESH","db_id":"D008770"}]},{"id":"26398","type":"Chemical","text":["testosterone propionate"],"offsets":[[301,324]],"normalized":[{"db_name":"MESH","db_id":"D043343"}]},{"id":"26399","type":"Chemical","text":["TP"],"offsets":[[327,329]],"normalized":[{"db_name":"MESH","db_id":"D043343"}]},{"id":"26400","type":"Disease","text":["tumor"],"offsets":[[362,367]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"26401","type":"Disease","text":["PA"],"offsets":[[524,526]],"normalized":[{"db_name":"MESH","db_id":"D011471"}]},{"id":"26402","type":"Chemical","text":["TP"],"offsets":[[550,552]],"normalized":[{"db_name":"MESH","db_id":"D043343"}]},{"id":"26403","type":"Chemical","text":["TP"],"offsets":[[567,569]],"normalized":[{"db_name":"MESH","db_id":"D043343"}]},{"id":"26404","type":"Disease","text":["tumor"],"offsets":[[581,586]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"26405","type":"Disease","text":["prostate cancer"],"offsets":[[650,665]],"normalized":[{"db_name":"MESH","db_id":"D011471"}]}],"events":[],"coreferences":[],"relations":[{"id":"26406","type":"CID","arg1_id":"26398","arg2_id":"26392","normalized":[]},{"id":"26407","type":"CID","arg1_id":"26398","arg2_id":"26395","normalized":[]},{"id":"26408","type":"CID","arg1_id":"26398","arg2_id":"26396","normalized":[]},{"id":"26409","type":"CID","arg1_id":"26398","arg2_id":"26401","normalized":[]},{"id":"26410","type":"CID","arg1_id":"26398","arg2_id":"26405","normalized":[]},{"id":"26411","type":"CID","arg1_id":"26399","arg2_id":"26392","normalized":[]},{"id":"26412","type":"CID","arg1_id":"26399","arg2_id":"26395","normalized":[]},{"id":"26413","type":"CID","arg1_id":"26399","arg2_id":"26396","normalized":[]},{"id":"26414","type":"CID","arg1_id":"26399","arg2_id":"26401","normalized":[]},{"id":"26415","type":"CID","arg1_id":"26399","arg2_id":"26405","normalized":[]},{"id":"26416","type":"CID","arg1_id":"26402","arg2_id":"26392","normalized":[]},{"id":"26417","type":"CID","arg1_id":"26402","arg2_id":"26395","normalized":[]},{"id":"26418","type":"CID","arg1_id":"26402","arg2_id":"26396","normalized":[]},{"id":"26419","type":"CID","arg1_id":"26402","arg2_id":"26401","normalized":[]},{"id":"26420","type":"CID","arg1_id":"26402","arg2_id":"26405","normalized":[]},{"id":"26421","type":"CID","arg1_id":"26403","arg2_id":"26392","normalized":[]},{"id":"26422","type":"CID","arg1_id":"26403","arg2_id":"26395","normalized":[]},{"id":"26423","type":"CID","arg1_id":"26403","arg2_id":"26396","normalized":[]},{"id":"26424","type":"CID","arg1_id":"26403","arg2_id":"26401","normalized":[]},{"id":"26425","type":"CID","arg1_id":"26403","arg2_id":"26405","normalized":[]},{"id":"26426","type":"CID","arg1_id":"26393","arg2_id":"26392","normalized":[]},{"id":"26427","type":"CID","arg1_id":"26393","arg2_id":"26395","normalized":[]},{"id":"26428","type":"CID","arg1_id":"26393","arg2_id":"26396","normalized":[]},{"id":"26429","type":"CID","arg1_id":"26393","arg2_id":"26401","normalized":[]},{"id":"26430","type":"CID","arg1_id":"26393","arg2_id":"26405","normalized":[]},{"id":"26431","type":"CID","arg1_id":"26397","arg2_id":"26392","normalized":[]},{"id":"26432","type":"CID","arg1_id":"26397","arg2_id":"26395","normalized":[]},{"id":"26433","type":"CID","arg1_id":"26397","arg2_id":"26396","normalized":[]},{"id":"26434","type":"CID","arg1_id":"26397","arg2_id":"26401","normalized":[]},{"id":"26435","type":"CID","arg1_id":"26397","arg2_id":"26405","normalized":[]}]}
{"id":"26436","document_id":"2840807","passages":[{"id":"26437","type":"title","text":["A dystonia-like syndrome after neuropeptide (MSH\/ACTH) stimulation of the rat locus ceruleus."],"offsets":[[0,93]]},{"id":"26438","type":"abstract","text":["The movement disorder investigated in these studies has some features in common with human idiopathic dystonia, and information obtained in these studies may be of potential clinical benefit. The present experimental results indicated that peptidergic stimulation of the LC resulted in a NE-mediated inhibition of cerebellar Purkinje cells located at terminals of the ceruleo-cerebellar pathway. However, it is not certain as to the following: (a) what receptors were stimulated by the ACTH N-terminal fragments at the LC that resulted in this disorder; (b) whether NE, released onto Purkinje cell synapses located at terminals of the ceruleo-cerebellar pathway, did indeed cause the long-term depression at Purkinje cell synapses (previously described by others) that resulted in the long duration of the movement disorder; (c) whether the inhibition of inhibitory Purkinje cells resulted in disinhibition or increased excitability of the unilateral cerebellar fastigial or interpositus nuclei, the output targets of the Purkinje cell axons, that may have been an important contributing factor to this disorder. These questions are currently being investigated."],"offsets":[[94,1256]]}],"entities":[{"id":"26439","type":"Disease","text":["dystonia"],"offsets":[[2,10]],"normalized":[{"db_name":"MESH","db_id":"D004421"}]},{"id":"26440","type":"Chemical","text":["MSH"],"offsets":[[45,48]],"normalized":[{"db_name":"MESH","db_id":"D009074"}]},{"id":"26441","type":"Chemical","text":["ACTH"],"offsets":[[49,53]],"normalized":[{"db_name":"MESH","db_id":"D000324"}]},{"id":"26442","type":"Disease","text":["movement disorder"],"offsets":[[98,115]],"normalized":[{"db_name":"MESH","db_id":"D009069"}]},{"id":"26443","type":"Disease","text":["dystonia"],"offsets":[[196,204]],"normalized":[{"db_name":"MESH","db_id":"D004421"}]},{"id":"26444","type":"Chemical","text":["ACTH"],"offsets":[[580,584]],"normalized":[{"db_name":"MESH","db_id":"D000324"}]},{"id":"26445","type":"Disease","text":["depression"],"offsets":[[788,798]],"normalized":[{"db_name":"MESH","db_id":"D003866"}]},{"id":"26446","type":"Disease","text":["movement disorder"],"offsets":[[900,917]],"normalized":[{"db_name":"MESH","db_id":"D009069"}]}],"events":[],"coreferences":[],"relations":[{"id":"26447","type":"CID","arg1_id":"26440","arg2_id":"26439","normalized":[]},{"id":"26448","type":"CID","arg1_id":"26440","arg2_id":"26443","normalized":[]},{"id":"26449","type":"CID","arg1_id":"26441","arg2_id":"26439","normalized":[]},{"id":"26450","type":"CID","arg1_id":"26441","arg2_id":"26443","normalized":[]},{"id":"26451","type":"CID","arg1_id":"26444","arg2_id":"26439","normalized":[]},{"id":"26452","type":"CID","arg1_id":"26444","arg2_id":"26443","normalized":[]}]}
{"id":"26453","document_id":"2569282","passages":[{"id":"26454","type":"title","text":["Dexmedetomidine, acting through central alpha-2 adrenoceptors, prevents opiate-induced muscle rigidity in the rat."],"offsets":[[0,114]]},{"id":"26455","type":"abstract","text":["The highly-selective alpha-2 adrenergic agonist dexmedetomidine (D-MED) is capable of inducing muscle flaccidity and anesthesia in rats and dogs. Intense generalized muscle rigidity is an undesirable side effect of potent opiate agonists. Although the neurochemistry of opiate-induced rigidity has yet to be fully elucidated, recent work suggests a role for a central adrenergic mechanism. In the present study, the authors determined if treatment with D-MED prevents the muscle rigidity caused by high-dose alfentanil anesthesia in the rat. Animals (n = 42) were treated intraperitoneally with one of the following six regimens: 1) L-MED (the inactive L-isomer of medetomidine), 30 micrograms\/kg; 2) D-MED, 10 micrograms\/kg; 3) D-MED, 30 micrograms\/kg; 4) D-MED [30 micrograms\/kg] and the central-acting alpha-2 antagonist, idazoxan [10 mg\/kg]; 5) D-MED [30 micrograms\/kg] and the peripheral-acting alpha-2 antagonist DG-5128 [10 mg\/kg], or; 6) saline. Baseline electromyographic activity was recorded from the gastrocnemius muscle before and after drug treatment. Each rat was then injected with alfentanil (ALF, 0.5 mg\/kg sc). ALF injection resulted in a marked increase in hindlimb EMG activity in the L-MED treatment group which was indistinguishable from that seen in animals treated with saline. In contrast, D-MED prevented alfentanil-induced muscle rigidity in a dose-dependent fashion. The small EMG values obtained in the high-dose D-MED group were comparable with those recorded in earlier studies from control animals not given any opiate. The high-dose D-MED animals were flaccid, akinetic, and lacked a startle response during the entire experimental period.(ABSTRACT TRUNCATED AT 250 WORDS)"],"offsets":[[115,1821]]}],"entities":[{"id":"26456","type":"Chemical","text":["Dexmedetomidine"],"offsets":[[0,15]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"26457","type":"Disease","text":["muscle rigidity"],"offsets":[[87,102]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"26458","type":"Chemical","text":["dexmedetomidine"],"offsets":[[163,178]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"26459","type":"Chemical","text":["D-MED"],"offsets":[[180,185]],"normalized":[{"db_name":"MESH","db_id":"D020927"}]},{"id":"26460","type":"Disease","text":["muscle flaccidity"],"offsets":[[210,227]],"normalized":[{"db_name":"MESH","db_id":"D009123"}]},{"id":"26461","type":"Disease","text":["muscle 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{"id":"26508","document_id":"2343592","passages":[{"id":"26509","type":"title","text":["Seizure activity with imipenem therapy: incidence and risk factors."],"offsets":[[0,67]]},{"id":"26510","type":"abstract","text":["Two elderly patients with a history of either cerebral vascular accident (CVA) or head trauma and no evidence of renal disease developed seizures while receiving maximum doses of imipenem\/cilastatin. Neither patient had reported previous seizures or seizure-like activity nor was receiving anticonvulsant agents. All seizures were controlled with therapeutic doses of phenytoin. Both patients had received maximum doses of other beta-lactam antibiotics without evidence of seizure activity."],"offsets":[[68,558]]}],"entities":[{"id":"26511","type":"Disease","text":["Seizure"],"offsets":[[0,7]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"26512","type":"Chemical","text":["imipenem"],"offsets":[[22,30]],"normalized":[{"db_name":"MESH","db_id":"D015378"}]},{"id":"26513","type":"Disease","text":["cerebral vascular accident"],"offsets":[[114,140]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"26514","type":"Disease","text":["CVA"],"offsets":[[142,145]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"26515","type":"Disease","text":["head trauma"],"offsets":[[150,161]],"normalized":[{"db_name":"MESH","db_id":"D006259"}]},{"id":"26516","type":"Disease","text":["renal disease"],"offsets":[[181,194]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"26517","type":"Disease","text":["seizures"],"offsets":[[205,213]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"26518","type":"Chemical","text":["imipenem\/cilastatin"],"offsets":[[247,266]],"normalized":[{"db_name":"MESH","db_id":"C044650"}]},{"id":"26519","type":"Disease","text":["seizures"],"offsets":[[306,314]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"26520","type":"Disease","text":["seizure"],"offsets":[[318,325]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"26521","type":"Disease","text":["seizures"],"offsets":[[385,393]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"26522","type":"Chemical","text":["phenytoin"],"offsets":[[436,445]],"normalized":[{"db_name":"MESH","db_id":"D010672"}]},{"id":"26523","type":"Chemical","text":["beta-lactam"],"offsets":[[497,508]],"normalized":[{"db_name":"MESH","db_id":"D047090"}]},{"id":"26524","type":"Disease","text":["seizure"],"offsets":[[541,548]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]}],"events":[],"coreferences":[],"relations":[{"id":"26525","type":"CID","arg1_id":"26518","arg2_id":"26511","normalized":[]},{"id":"26526","type":"CID","arg1_id":"26518","arg2_id":"26517","normalized":[]},{"id":"26527","type":"CID","arg1_id":"26518","arg2_id":"26519","normalized":[]},{"id":"26528","type":"CID","arg1_id":"26518","arg2_id":"26520","normalized":[]},{"id":"26529","type":"CID","arg1_id":"26518","arg2_id":"26521","normalized":[]},{"id":"26530","type":"CID","arg1_id":"26518","arg2_id":"26524","normalized":[]}]}
{"id":"26531","document_id":"2055425","passages":[{"id":"26532","type":"title","text":["The ability of insulin treatment to reverse or prevent the changes in urinary bladder function caused by streptozotocin-induced diabetes mellitus."],"offsets":[[0,146]]},{"id":"26533","type":"abstract","text":["1. The effects of insulin treatment on in vivo and in vitro urinary bladder function in streptozotocin-diabetic rats were investigated. 2. Diabetes of 2 months duration resulted in decreases in body weight and increases in fluid consumption, urine volume, frequency of micturition, and average volume per micturition; effects which were prevented by insulin treatment. 3. Insulin treatment also prevented the increases in contractile responses of bladder body strips from diabetic rats to nerve stimulation, ATP, and bethanechol. 4. Diabetes of 4 months duration also resulted in decreases in body weight, and increases in fluid consumption, urine volume, frequency of micturition, and average volume per micturition, effects which were reversed by insulin treatment for the final 2 months of the study. 5. Insulin treatment reversed the increases in contractile responses of bladder body strips from diabetic rats to nerve stimulation, ATP, and bethanechol. 6. The data indicate that the effects of streptozotocin-induced diabetes on urinary bladder function are both prevented and reversed by insulin treatment."],"offsets":[[147,1260]]}],"entities":[{"id":"26534","type":"Chemical","text":["streptozotocin"],"offsets":[[105,119]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"26535","type":"Disease","text":["diabetes mellitus"],"offsets":[[128,145]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"26536","type":"Chemical","text":["streptozotocin"],"offsets":[[235,249]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"26537","type":"Disease","text":["diabetic"],"offsets":[[250,258]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"26538","type":"Disease","text":["Diabetes"],"offsets":[[286,294]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"26539","type":"Disease","text":["diabetic"],"offsets":[[619,627]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"26540","type":"Chemical","text":["ATP"],"offsets":[[655,658]],"normalized":[{"db_name":"MESH","db_id":"D000255"}]},{"id":"26541","type":"Chemical","text":["bethanechol"],"offsets":[[664,675]],"normalized":[{"db_name":"MESH","db_id":"D018723"}]},{"id":"26542","type":"Disease","text":["Diabetes"],"offsets":[[680,688]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"26543","type":"Disease","text":["diabetic"],"offsets":[[1048,1056]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]},{"id":"26544","type":"Chemical","text":["ATP"],"offsets":[[1084,1087]],"normalized":[{"db_name":"MESH","db_id":"D000255"}]},{"id":"26545","type":"Chemical","text":["bethanechol"],"offsets":[[1093,1104]],"normalized":[{"db_name":"MESH","db_id":"D018723"}]},{"id":"26546","type":"Chemical","text":["streptozotocin"],"offsets":[[1147,1161]],"normalized":[{"db_name":"MESH","db_id":"D013311"}]},{"id":"26547","type":"Disease","text":["diabetes"],"offsets":[[1170,1178]],"normalized":[{"db_name":"MESH","db_id":"D003920"}]}],"events":[],"coreferences":[],"relations":[{"id":"26548","type":"CID","arg1_id":"26534","arg2_id":"26535","normalized":[]},{"id":"26549","type":"CID","arg1_id":"26534","arg2_id":"26537","normalized":[]},{"id":"26550","type":"CID","arg1_id":"26534","arg2_id":"26538","normalized":[]},{"id":"26551","type":"CID","arg1_id":"26534","arg2_id":"26539","normalized":[]},{"id":"26552","type":"CID","arg1_id":"26534","arg2_id":"26542","normalized":[]},{"id":"26553","type":"CID","arg1_id":"26534","arg2_id":"26543","normalized":[]},{"id":"26554","type":"CID","arg1_id":"26534","arg2_id":"26547","normalized":[]},{"id":"26555","type":"CID","arg1_id":"26536","arg2_id":"26535","normalized":[]},{"id":"26556","type":"CID","arg1_id":"26536","arg2_id":"26537","normalized":[]},{"id":"26557","type":"CID","arg1_id":"26536","arg2_id":"26538","normalized":[]},{"id":"26558","type":"CID","arg1_id":"26536","arg2_id":"26539","normalized":[]},{"id":"26559","type":"CID","arg1_id":"26536","arg2_id":"26542","normalized":[]},{"id":"26560","type":"CID","arg1_id":"26536","arg2_id":"26543","normalized":[]},{"id":"26561","type":"CID","arg1_id":"26536","arg2_id":"26547","normalized":[]},{"id":"26562","type":"CID","arg1_id":"26546","arg2_id":"26535","normalized":[]},{"id":"26563","type":"CID","arg1_id":"26546","arg2_id":"26537","normalized":[]},{"id":"26564","type":"CID","arg1_id":"26546","arg2_id":"26538","normalized":[]},{"id":"26565","type":"CID","arg1_id":"26546","arg2_id":"26539","normalized":[]},{"id":"26566","type":"CID","arg1_id":"26546","arg2_id":"26542","normalized":[]},{"id":"26567","type":"CID","arg1_id":"26546","arg2_id":"26543","normalized":[]},{"id":"26568","type":"CID","arg1_id":"26546","arg2_id":"26547","normalized":[]}]}
{"id":"26569","document_id":"1711760","passages":[{"id":"26570","type":"title","text":["Delayed institution of hypertension during focal cerebral ischemia: effect on brain edema."],"offsets":[[0,90]]},{"id":"26571","type":"abstract","text":["The effect of induced hypertension instituted after a 2-h delay following middle cerebral artery occlusion (MCAO) on brain edema formation and histochemical injury was studied. Under isoflurane anesthesia, the MCA of 14 spontaneously hypertensive rats was occluded. In the control group (n = 7), the mean arterial pressure (MAP) was not manipulated. In the hypertensive group (n = 7), the MAP was elevated by 25-30 mm Hg beginning 2 h after MCAO. Four hours after MCAO, the rats were killed and the brains harvested. The brains were sectioned along coronal planes spanning the distribution of ischemia produced by MCAO. Specific gravity (SG) was determined in the subcortex and in two sites in the cortex (core and periphery of the ischemic territory). The extent of neuronal injury was determined by 2,3,5-triphenyltetrazolium staining. In the ischemic core, there was no difference in SG in the subcortex and cortex in the two groups. In the periphery of the ischemic territory, SG in the cortex was greater (less edema accumulation) in the hypertensive group (1.041 +\/- 0.001 vs 1.039 +\/- 0.001, P less than 0.05). The area of histochemical injury (as a percent of the cross-sectional area of the hemisphere) was less in the hypertensive group (33 +\/- 3% vs 21 +\/- 2%, P less than 0.05). The data indicate that phenylephrine-induced hypertension instituted 2 h after MCAO does not aggravate edema in the ischemic core, that it improves edema in the periphery of the ischemic territory, and that it reduces the area of histochemical neuronal dysfunction."],"offsets":[[91,1647]]}],"entities":[{"id":"26572","type":"Disease","text":["hypertension"],"offsets":[[23,35]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"26573","type":"Disease","text":["cerebral ischemia"],"offsets":[[49,66]],"normalized":[{"db_name":"MESH","db_id":"D002545"}]},{"id":"26574","type":"Disease","text":["brain edema"],"offsets":[[78,89]],"normalized":[{"db_name":"MESH","db_id":"D001929"}]},{"id":"26575","type":"Disease","text":["hypertension"],"offsets":[[113,125]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"26576","type":"Disease","text":["middle cerebral artery occlusion"],"offsets":[[165,197]],"normalized":[{"db_name":"MESH","db_id":"D020244"}]},{"id":"26577","type":"Disease","text":["MCAO"],"offsets":[[199,203]],"normalized":[{"db_name":"MESH","db_id":"D020244"}]},{"id":"26578","type":"Disease","text":["brain edema"],"offsets":[[208,219]],"normalized":[{"db_name":"MESH","db_id":"D001929"}]},{"id":"26579","type":"Chemical","text":["isoflurane"],"offsets":[[274,284]],"normalized":[{"db_name":"MESH","db_id":"D007530"}]},{"id":"26580","type":"Disease","text":["hypertensive"],"offsets":[[325,337]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"26581","type":"Disease","text":["hypertensive"],"offsets":[[448,460]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"26582","type":"Disease","text":["MCAO"],"offsets":[[532,536]],"normalized":[{"db_name":"MESH","db_id":"D020244"}]},{"id":"26583","type":"Disease","text":["MCAO"],"offsets":[[555,559]],"normalized":[{"db_name":"MESH","db_id":"D020244"}]},{"id":"26584","type":"Disease","text":["ischemia"],"offsets":[[684,692]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"26585","type":"Disease","text":["MCAO"],"offsets":[[705,709]],"normalized":[{"db_name":"MESH","db_id":"D020244"}]},{"id":"26586","type":"Disease","text":["ischemic"],"offsets":[[823,831]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"26587","type":"Disease","text":["neuronal injury"],"offsets":[[858,873]],"normalized":[{"db_name":"MESH","db_id":"D009410"}]},{"id":"26588","type":"Chemical","text":["2,3,5-triphenyltetrazolium"],"offsets":[[892,918]],"normalized":[{"db_name":"MESH","db_id":"C009591"}]},{"id":"26589","type":"Disease","text":["ischemic"],"offsets":[[936,944]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"26590","type":"Disease","text":["ischemic"],"offsets":[[1052,1060]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"26591","type":"Disease","text":["edema"],"offsets":[[1107,1112]],"normalized":[{"db_name":"MESH","db_id":"D004487"}]},{"id":"26592","type":"Disease","text":["hypertensive"],"offsets":[[1134,1146]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"26593","type":"Disease","text":["hypertensive"],"offsets":[[1319,1331]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"26594","type":"Chemical","text":["phenylephrine"],"offsets":[[1405,1418]],"normalized":[{"db_name":"MESH","db_id":"D010656"}]},{"id":"26595","type":"Disease","text":["hypertension"],"offsets":[[1427,1439]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"26596","type":"Disease","text":["MCAO"],"offsets":[[1461,1465]],"normalized":[{"db_name":"MESH","db_id":"D020244"}]},{"id":"26597","type":"Disease","text":["edema"],"offsets":[[1485,1490]],"normalized":[{"db_name":"MESH","db_id":"D004487"}]},{"id":"26598","type":"Disease","text":["ischemic"],"offsets":[[1498,1506]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"26599","type":"Disease","text":["edema"],"offsets":[[1530,1535]],"normalized":[{"db_name":"MESH","db_id":"D004487"}]},{"id":"26600","type":"Disease","text":["ischemic"],"offsets":[[1560,1568]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"26601","type":"Disease","text":["neuronal dysfunction"],"offsets":[[1626,1646]],"normalized":[{"db_name":"MESH","db_id":"D009410"}]}],"events":[],"coreferences":[],"relations":[{"id":"26602","type":"CID","arg1_id":"26594","arg2_id":"26572","normalized":[]},{"id":"26603","type":"CID","arg1_id":"26594","arg2_id":"26575","normalized":[]},{"id":"26604","type":"CID","arg1_id":"26594","arg2_id":"26580","normalized":[]},{"id":"26605","type":"CID","arg1_id":"26594","arg2_id":"26581","normalized":[]},{"id":"26606","type":"CID","arg1_id":"26594","arg2_id":"26592","normalized":[]},{"id":"26607","type":"CID","arg1_id":"26594","arg2_id":"26593","normalized":[]},{"id":"26608","type":"CID","arg1_id":"26594","arg2_id":"26595","normalized":[]}]}
{"id":"26609","document_id":"1595783","passages":[{"id":"26610","type":"title","text":["Amiodarone pulmonary toxicity."],"offsets":[[0,30]]},{"id":"26611","type":"abstract","text":["Amiodarone is an effective antiarrhythmic agent whose utility is limited by many side-effects, the most problematic being pneumonitis. The pulmonary toxicity of amiodarone is thought to result from direct injury related to the intracellular accumulation of phospholipid and T cell-mediated hypersensitivity pneumonitis. The clinical and radiographic features of amiodarone-induced pulmonary toxicity are characteristic but nonspecific. The diagnosis depends on exclusion of other entities, such as heart failure, infection, and malignancy. While withdrawal of amiodarone leads to clinical improvement in majority of cases, this is not always possible or advisable. Dose reduction or concomitant steroid therapy may have a role in selected patients."],"offsets":[[31,779]]}],"entities":[{"id":"26612","type":"Chemical","text":["Amiodarone"],"offsets":[[0,10]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"26613","type":"Disease","text":["pulmonary toxicity"],"offsets":[[11,29]],"normalized":[{"db_name":"MESH","db_id":"D008171"}]},{"id":"26614","type":"Chemical","text":["Amiodarone"],"offsets":[[31,41]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"26615","type":"Disease","text":["pneumonitis"],"offsets":[[153,164]],"normalized":[{"db_name":"MESH","db_id":"D011014"}]},{"id":"26616","type":"Disease","text":["pulmonary toxicity"],"offsets":[[170,188]],"normalized":[{"db_name":"MESH","db_id":"D008171"}]},{"id":"26617","type":"Chemical","text":["amiodarone"],"offsets":[[192,202]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"26618","type":"Disease","text":["hypersensitivity pneumonitis"],"offsets":[[321,349]],"normalized":[{"db_name":"MESH","db_id":"D004342"},{"db_name":"MESH","db_id":"D000542"}]},{"id":"26619","type":"Disease","text":["hypersensitivity"],"offsets":[[321,337]],"normalized":[{"db_name":"MESH","db_id":"D004342"}]},{"id":"26620","type":"Disease","text":["pneumonitis"],"offsets":[[338,349]],"normalized":[{"db_name":"MESH","db_id":"D000542"}]},{"id":"26621","type":"Chemical","text":["amiodarone"],"offsets":[[393,403]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"26622","type":"Disease","text":["pulmonary toxicity"],"offsets":[[412,430]],"normalized":[{"db_name":"MESH","db_id":"D008171"}]},{"id":"26623","type":"Disease","text":["heart failure"],"offsets":[[529,542]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"26624","type":"Disease","text":["infection"],"offsets":[[544,553]],"normalized":[{"db_name":"MESH","db_id":"D007239"}]},{"id":"26625","type":"Disease","text":["malignancy"],"offsets":[[559,569]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"26626","type":"Chemical","text":["amiodarone"],"offsets":[[591,601]],"normalized":[{"db_name":"MESH","db_id":"D000638"}]},{"id":"26627","type":"Chemical","text":["steroid"],"offsets":[[726,733]],"normalized":[{"db_name":"MESH","db_id":"D013256"}]}],"events":[],"coreferences":[],"relations":[{"id":"26628","type":"CID","arg1_id":"26612","arg2_id":"26615","normalized":[]},{"id":"26629","type":"CID","arg1_id":"26614","arg2_id":"26615","normalized":[]},{"id":"26630","type":"CID","arg1_id":"26617","arg2_id":"26615","normalized":[]},{"id":"26631","type":"CID","arg1_id":"26621","arg2_id":"26615","normalized":[]},{"id":"26632","type":"CID","arg1_id":"26626","arg2_id":"26615","normalized":[]},{"id":"26633","type":"CID","arg1_id":"26612","arg2_id":"26618","normalized":[]},{"id":"26634","type":"CID","arg1_id":"26612","arg2_id":"26619","normalized":[]},{"id":"26635","type":"CID","arg1_id":"26614","arg2_id":"26618","normalized":[]},{"id":"26636","type":"CID","arg1_id":"26614","arg2_id":"26619","normalized":[]},{"id":"26637","type":"CID","arg1_id":"26617","arg2_id":"26618","normalized":[]},{"id":"26638","type":"CID","arg1_id":"26617","arg2_id":"26619","normalized":[]},{"id":"26639","type":"CID","arg1_id":"26621","arg2_id":"26618","normalized":[]},{"id":"26640","type":"CID","arg1_id":"26621","arg2_id":"26619","normalized":[]},{"id":"26641","type":"CID","arg1_id":"26626","arg2_id":"26618","normalized":[]},{"id":"26642","type":"CID","arg1_id":"26626","arg2_id":"26619","normalized":[]}]}
{"id":"26643","document_id":"804391","passages":[{"id":"26644","type":"title","text":["Light chain proteinuria and cellular mediated immunity in rifampin treated patients with tuberculosis."],"offsets":[[0,102]]},{"id":"26645","type":"abstract","text":["Light chain proteinuria was found in 9 of 17 tuberculosis patients treated with rifampin. Concomitant assay of cellular mediated immunity in these patients using skin test antigen and a lymphokine in vitro test provided results that were different. Response to Varidase skin test antigen was negative for all eight tuberculosis patients tested, but there occurred a hyper-responsiveness of the lymphocytes of these eight patients to phytomitogen (PHA-P). as well as of those of seven other tuberculous patients. This last finding may be related to time of testing and\/or endogenous serum binding of rifampin which could have inhibited mitogen activity for the lymphocyte."],"offsets":[[103,774]]}],"entities":[{"id":"26646","type":"Disease","text":["proteinuria"],"offsets":[[12,23]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"26647","type":"Chemical","text":["rifampin"],"offsets":[[58,66]],"normalized":[{"db_name":"MESH","db_id":"D012293"}]},{"id":"26648","type":"Disease","text":["tuberculosis"],"offsets":[[89,101]],"normalized":[{"db_name":"MESH","db_id":"D014376"}]},{"id":"26649","type":"Disease","text":["proteinuria"],"offsets":[[115,126]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"26650","type":"Disease","text":["tuberculosis"],"offsets":[[148,160]],"normalized":[{"db_name":"MESH","db_id":"D014376"}]},{"id":"26651","type":"Chemical","text":["rifampin"],"offsets":[[183,191]],"normalized":[{"db_name":"MESH","db_id":"D012293"}]},{"id":"26652","type":"Disease","text":["tuberculosis"],"offsets":[[418,430]],"normalized":[{"db_name":"MESH","db_id":"D014376"}]},{"id":"26653","type":"Disease","text":["tuberculous"],"offsets":[[593,604]],"normalized":[{"db_name":"MESH","db_id":"D014376"}]},{"id":"26654","type":"Chemical","text":["rifampin"],"offsets":[[702,710]],"normalized":[{"db_name":"MESH","db_id":"D012293"}]}],"events":[],"coreferences":[],"relations":[{"id":"26655","type":"CID","arg1_id":"26647","arg2_id":"26646","normalized":[]},{"id":"26656","type":"CID","arg1_id":"26647","arg2_id":"26649","normalized":[]},{"id":"26657","type":"CID","arg1_id":"26651","arg2_id":"26646","normalized":[]},{"id":"26658","type":"CID","arg1_id":"26651","arg2_id":"26649","normalized":[]},{"id":"26659","type":"CID","arg1_id":"26654","arg2_id":"26646","normalized":[]},{"id":"26660","type":"CID","arg1_id":"26654","arg2_id":"26649","normalized":[]}]}
{"id":"26661","document_id":"28952","passages":[{"id":"26662","type":"title","text":["Initial potassium loss and hypokalaemia during chlorthalidone administration in patients with essential hypertension: the influence of dietary sodium restriction."],"offsets":[[0,162]]},{"id":"26663","type":"abstract","text":["To investigate the initial potassium loss and development of hypokalaemia during the administration of an oral diuretic, metabolic balance studies were performed in ten patients with essential hypertension who had shown hypokalaemia under prior oral diuretic treatment. Chlorthalidone (50 mg daily) was given for 14 days. Six patients received a normal-sodium diet and four a low-sodium (17 mmol\/day) diet. All patients had a normal initial total body potassium (40K). The electrolyte balances, weight, bromide space, plasma renin activity, and aldosterone secretion rate were measured. In both groups a potassium deficit developed, with proportionally larger losses from the extracellular than from the intracellular compartment. In the normal-sodium group the highest mean potassium deficit was 176 mmol on day 9, after which some potassium was regained; in the low-sodium group the highest deficit was 276 mmol on day 13. The normal-sodium group showed an immediate but temporary rise of the renin and aldosterone levels; in the low-sodium group renin and aldosterone increased more slowly but remained elevated. It is concluded that dietary sodium restriction increases diuretic-induced potassium loss, presumably by an increased activity of the renin-angiotensin-aldosterone system, while sodium delivery to the distal renal tubules remains sufficiently high to allow increased potassium secretion."],"offsets":[[163,1566]]}],"entities":[{"id":"26664","type":"Chemical","text":["potassium"],"offsets":[[8,17]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"26665","type":"Disease","text":["hypokalaemia"],"offsets":[[27,39]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"26666","type":"Chemical","text":["chlorthalidone"],"offsets":[[47,61]],"normalized":[{"db_name":"MESH","db_id":"D002752"}]},{"id":"26667","type":"Disease","text":["hypertension"],"offsets":[[104,116]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"26668","type":"Chemical","text":["sodium"],"offsets":[[143,149]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"26669","type":"Chemical","text":["potassium"],"offsets":[[190,199]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"26670","type":"Disease","text":["hypokalaemia"],"offsets":[[224,236]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"26671","type":"Disease","text":["hypertension"],"offsets":[[356,368]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"26672","type":"Disease","text":["hypokalaemia"],"offsets":[[383,395]],"normalized":[{"db_name":"MESH","db_id":"D007008"}]},{"id":"26673","type":"Chemical","text":["Chlorthalidone"],"offsets":[[433,447]],"normalized":[{"db_name":"MESH","db_id":"D002752"}]},{"id":"26674","type":"Chemical","text":["sodium"],"offsets":[[516,522]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"26675","type":"Chemical","text":["sodium"],"offsets":[[543,549]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"26676","type":"Chemical","text":["potassium"],"offsets":[[615,624]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"26677","type":"Chemical","text":["aldosterone"],"offsets":[[708,719]],"normalized":[{"db_name":"MESH","db_id":"D000450"}]},{"id":"26678","type":"Chemical","text":["potassium"],"offsets":[[767,776]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"26679","type":"Chemical","text":["sodium"],"offsets":[[908,914]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"26680","type":"Chemical","text":["potassium"],"offsets":[[938,947]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"26681","type":"Chemical","text":["potassium"],"offsets":[[996,1005]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"26682","type":"Chemical","text":["sodium"],"offsets":[[1031,1037]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"26683","type":"Chemical","text":["sodium"],"offsets":[[1099,1105]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"26684","type":"Chemical","text":["aldosterone"],"offsets":[[1168,1179]],"normalized":[{"db_name":"MESH","db_id":"D000450"}]},{"id":"26685","type":"Chemical","text":["sodium"],"offsets":[[1199,1205]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"26686","type":"Chemical","text":["aldosterone"],"offsets":[[1222,1233]],"normalized":[{"db_name":"MESH","db_id":"D000450"}]},{"id":"26687","type":"Chemical","text":["sodium"],"offsets":[[1308,1314]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"26688","type":"Chemical","text":["potassium"],"offsets":[[1354,1363]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"26689","type":"Chemical","text":["angiotensin"],"offsets":[[1419,1430]],"normalized":[{"db_name":"MESH","db_id":"D000809"}]},{"id":"26690","type":"Chemical","text":["aldosterone"],"offsets":[[1431,1442]],"normalized":[{"db_name":"MESH","db_id":"D000450"}]},{"id":"26691","type":"Chemical","text":["sodium"],"offsets":[[1457,1463]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"26692","type":"Chemical","text":["potassium"],"offsets":[[1546,1555]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]}],"events":[],"coreferences":[],"relations":[{"id":"26693","type":"CID","arg1_id":"26666","arg2_id":"26665","normalized":[]},{"id":"26694","type":"CID","arg1_id":"26666","arg2_id":"26670","normalized":[]},{"id":"26695","type":"CID","arg1_id":"26666","arg2_id":"26672","normalized":[]},{"id":"26696","type":"CID","arg1_id":"26673","arg2_id":"26665","normalized":[]},{"id":"26697","type":"CID","arg1_id":"26673","arg2_id":"26670","normalized":[]},{"id":"26698","type":"CID","arg1_id":"26673","arg2_id":"26672","normalized":[]}]}
{"id":"26699","document_id":"19893084","passages":[{"id":"26700","type":"title","text":["Dynamic response of blood vessel in acute renal failure."],"offsets":[[0,56]]},{"id":"26701","type":"abstract","text":["In this study we postulated that during acute renal failure induced by gentamicin the transient or dynamic response of blood vessels could be affected, and that antioxidants can prevent the changes in dynamic responses of blood vessels. The new approach to ex vivo blood vessel experiments in which not only the end points of vessels response within the time interval is considered, but also dynamics of this response, was used in this paper. Our results confirm the alteration in dynamic response of blood vessels during the change of pressure in gentamicin-treated animals. The beneficial effects of vitamin C administration to gentamicin-treated animals are also confirmed through: lower level of blood urea and creatinine and higher level of potassium. The pressure dynamic responses of isolated blood vessels show a faster pressure change in gentamicin-treated animals (8.07 +\/- 1.7 s vs. 5.64 +\/- 0.18 s). Vitamin C administration induced slowdown of pressure change back to the control values. The pressure dynamic properties, quantitatively defined by comparative pressure dynamic and total pressure dynamic, confirm the alteration in dynamic response of blood vessels during the change of pressure in gentamicin-treated animals and beneficial effects of vitamin C administration."],"offsets":[[57,1345]]}],"entities":[{"id":"26702","type":"Disease","text":["acute renal failure"],"offsets":[[36,55]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"26703","type":"Disease","text":["acute renal failure"],"offsets":[[97,116]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"26704","type":"Chemical","text":["gentamicin"],"offsets":[[128,138]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"26705","type":"Chemical","text":["gentamicin"],"offsets":[[605,615]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"26706","type":"Chemical","text":["vitamin C"],"offsets":[[659,668]],"normalized":[{"db_name":"MESH","db_id":"D001205"}]},{"id":"26707","type":"Chemical","text":["gentamicin"],"offsets":[[687,697]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"26708","type":"Chemical","text":["urea"],"offsets":[[763,767]],"normalized":[{"db_name":"MESH","db_id":"D014508"}]},{"id":"26709","type":"Chemical","text":["creatinine"],"offsets":[[772,782]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"26710","type":"Chemical","text":["potassium"],"offsets":[[803,812]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"26711","type":"Chemical","text":["gentamicin"],"offsets":[[904,914]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"26712","type":"Chemical","text":["Vitamin C"],"offsets":[[969,978]],"normalized":[{"db_name":"MESH","db_id":"D001205"}]},{"id":"26713","type":"Chemical","text":["gentamicin"],"offsets":[[1267,1277]],"normalized":[{"db_name":"MESH","db_id":"D005839"}]},{"id":"26714","type":"Chemical","text":["vitamin C"],"offsets":[[1320,1329]],"normalized":[{"db_name":"MESH","db_id":"D001205"}]}],"events":[],"coreferences":[],"relations":[{"id":"26715","type":"CID","arg1_id":"26704","arg2_id":"26702","normalized":[]},{"id":"26716","type":"CID","arg1_id":"26704","arg2_id":"26703","normalized":[]},{"id":"26717","type":"CID","arg1_id":"26705","arg2_id":"26702","normalized":[]},{"id":"26718","type":"CID","arg1_id":"26705","arg2_id":"26703","normalized":[]},{"id":"26719","type":"CID","arg1_id":"26707","arg2_id":"26702","normalized":[]},{"id":"26720","type":"CID","arg1_id":"26707","arg2_id":"26703","normalized":[]},{"id":"26721","type":"CID","arg1_id":"26711","arg2_id":"26702","normalized":[]},{"id":"26722","type":"CID","arg1_id":"26711","arg2_id":"26703","normalized":[]},{"id":"26723","type":"CID","arg1_id":"26713","arg2_id":"26702","normalized":[]},{"id":"26724","type":"CID","arg1_id":"26713","arg2_id":"26703","normalized":[]}]}
{"id":"26725","document_id":"18513945","passages":[{"id":"26726","type":"title","text":["The hemodynamics of oxytocin and other vasoactive agents during neuraxial anesthesia for cesarean delivery: findings in six cases."],"offsets":[[0,130]]},{"id":"26727","type":"abstract","text":["Oxytocin is a commonly used uterotonic that can cause significant and even fatal hypotension, particularly when given as a bolus. The resulting hypotension can be produced by a decrease in systemic vascular resistance or cardiac output through a decrease in venous return. Parturients with normal volume status, heart valves and pulmonary vasculature most often respond to this hypotension with a compensatory increase in heart rate and stroke volume. Oxytocin-induced hypotension at cesarean delivery may be incorrectly attributed to blood loss. Pulse power analysis (also called \"pulse contour analysis\") of an arterial pressure wave form allows continuous evaluation of systemic vascular resistance and cardiac output in real time, thereby elucidating the causative factors behind changes in blood pressure. Pulse power analysis was conducted in six cases of cesarean delivery performed under neuraxial anesthesia. Hypotension in response to oxytocin was associated with a decrease in systemic vascular resistance and a compensatory increase in stroke volume, heart rate and cardiac output. Pulse power analysis may be helpful in determining the etiology of and treating hypotension during cesarean delivery under neuraxial anesthesia."],"offsets":[[131,1369]]}],"entities":[{"id":"26728","type":"Chemical","text":["oxytocin"],"offsets":[[20,28]],"normalized":[{"db_name":"MESH","db_id":"D010121"}]},{"id":"26729","type":"Chemical","text":["Oxytocin"],"offsets":[[131,139]],"normalized":[{"db_name":"MESH","db_id":"D010121"}]},{"id":"26730","type":"Disease","text":["hypotension"],"offsets":[[212,223]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"26731","type":"Disease","text":["hypotension"],"offsets":[[275,286]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"26732","type":"Disease","text":["hypotension"],"offsets":[[509,520]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"26733","type":"Disease","text":["stroke"],"offsets":[[568,574]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"26734","type":"Chemical","text":["Oxytocin"],"offsets":[[583,591]],"normalized":[{"db_name":"MESH","db_id":"D010121"}]},{"id":"26735","type":"Disease","text":["hypotension"],"offsets":[[600,611]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"26736","type":"Disease","text":["blood loss"],"offsets":[[666,676]],"normalized":[{"db_name":"MESH","db_id":"D006473"}]},{"id":"26737","type":"Disease","text":["Hypotension"],"offsets":[[1049,1060]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"26738","type":"Chemical","text":["oxytocin"],"offsets":[[1076,1084]],"normalized":[{"db_name":"MESH","db_id":"D010121"}]},{"id":"26739","type":"Disease","text":["stroke"],"offsets":[[1179,1185]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"26740","type":"Disease","text":["hypotension"],"offsets":[[1305,1316]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]}],"events":[],"coreferences":[],"relations":[{"id":"26741","type":"CID","arg1_id":"26728","arg2_id":"26730","normalized":[]},{"id":"26742","type":"CID","arg1_id":"26728","arg2_id":"26731","normalized":[]},{"id":"26743","type":"CID","arg1_id":"26728","arg2_id":"26732","normalized":[]},{"id":"26744","type":"CID","arg1_id":"26728","arg2_id":"26735","normalized":[]},{"id":"26745","type":"CID","arg1_id":"26728","arg2_id":"26737","normalized":[]},{"id":"26746","type":"CID","arg1_id":"26728","arg2_id":"26740","normalized":[]},{"id":"26747","type":"CID","arg1_id":"26729","arg2_id":"26730","normalized":[]},{"id":"26748","type":"CID","arg1_id":"26729","arg2_id":"26731","normalized":[]},{"id":"26749","type":"CID","arg1_id":"26729","arg2_id":"26732","normalized":[]},{"id":"26750","type":"CID","arg1_id":"26729","arg2_id":"26735","normalized":[]},{"id":"26751","type":"CID","arg1_id":"26729","arg2_id":"26737","normalized":[]},{"id":"26752","type":"CID","arg1_id":"26729","arg2_id":"26740","normalized":[]},{"id":"26753","type":"CID","arg1_id":"26734","arg2_id":"26730","normalized":[]},{"id":"26754","type":"CID","arg1_id":"26734","arg2_id":"26731","normalized":[]},{"id":"26755","type":"CID","arg1_id":"26734","arg2_id":"26732","normalized":[]},{"id":"26756","type":"CID","arg1_id":"26734","arg2_id":"26735","normalized":[]},{"id":"26757","type":"CID","arg1_id":"26734","arg2_id":"26737","normalized":[]},{"id":"26758","type":"CID","arg1_id":"26734","arg2_id":"26740","normalized":[]},{"id":"26759","type":"CID","arg1_id":"26738","arg2_id":"26730","normalized":[]},{"id":"26760","type":"CID","arg1_id":"26738","arg2_id":"26731","normalized":[]},{"id":"26761","type":"CID","arg1_id":"26738","arg2_id":"26732","normalized":[]},{"id":"26762","type":"CID","arg1_id":"26738","arg2_id":"26735","normalized":[]},{"id":"26763","type":"CID","arg1_id":"26738","arg2_id":"26737","normalized":[]},{"id":"26764","type":"CID","arg1_id":"26738","arg2_id":"26740","normalized":[]}]}
{"id":"26765","document_id":"18483878","passages":[{"id":"26766","type":"title","text":["Exaggerated expression of inflammatory mediators in vasoactive intestinal polypeptide knockout (VIP-\/-) mice with cyclophosphamide (CYP)-induced cystitis."],"offsets":[[0,154]]},{"id":"26767","type":"abstract","text":["Vasoactive intestinal polypeptide (VIP) is an immunomodulatory neuropeptide distributed in micturition pathways. VIP(-\/-) mice exhibit altered bladder function and neurochemical properties in micturition pathways after cyclophosphamide (CYP)-induced cystitis. Given VIP's role as an anti-inflammatory mediator, we hypothesized that VIP(-\/-) mice would exhibit enhanced inflammatory mediator expression after cystitis. A mouse inflammatory cytokine and receptor RT2 profiler array was used to determine regulated transcripts in the urinary bladder of wild type (WT) and VIP(-\/-) mice with or without CYP-induced cystitis (150 mg\/kg; i.p.; 48 h). Four binary comparisons were made: WT control versus CYP treatment (48 h), VIP(-\/-) control versus CYP treatment (48 h), WT control versus VIP(-\/-) control, and WT with CYP treatment (48 h) versus VIP(-\/-) with CYP treatment (48 h). The genes presented represent (1) greater than 1.5-fold change in either direction and (2) the p value is less than 0.05 for the comparison being made. Several regulated genes were validated using enzyme-linked immunoassays including IL-1beta and CXCL1. CYP treatment significantly (p < or = 0.001) increased expression of CXCL1 and IL-1beta in the urinary bladder of WT and VIP(-\/-) mice, but expression in VIP(-\/-) mice with CYP treatment was significantly (p < or = 0.001) greater (4.2- to 13-fold increase) than that observed in WT urinary bladder (3.6- to 5-fold increase). The data suggest that in VIP(-\/-) mice with bladder inflammation, inflammatory mediators are increased above that observed in WT with CYP. This shift in balance may contribute to increased bladder dysfunction in VIP(-\/-) mice with bladder inflammation and altered neurochemical expression in micturition pathways."],"offsets":[[155,1925]]}],"entities":[{"id":"26768","type":"Chemical","text":["cyclophosphamide"],"offsets":[[114,130]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"26769","type":"Chemical","text":["CYP"],"offsets":[[132,135]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"26770","type":"Disease","text":["cystitis"],"offsets":[[145,153]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"26771","type":"Chemical","text":["cyclophosphamide"],"offsets":[[374,390]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"26772","type":"Chemical","text":["CYP"],"offsets":[[392,395]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"26773","type":"Disease","text":["cystitis"],"offsets":[[405,413]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"26774","type":"Disease","text":["cystitis"],"offsets":[[563,571]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"26775","type":"Chemical","text":["CYP"],"offsets":[[754,757]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"26776","type":"Disease","text":["cystitis"],"offsets":[[766,774]],"normalized":[{"db_name":"MESH","db_id":"D003556"}]},{"id":"26777","type":"Chemical","text":["CYP"],"offsets":[[853,856]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"26778","type":"Chemical","text":["CYP"],"offsets":[[899,902]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"26779","type":"Chemical","text":["CYP"],"offsets":[[969,972]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"26780","type":"Chemical","text":["CYP"],"offsets":[[1011,1014]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"26781","type":"Chemical","text":["CYP"],"offsets":[[1287,1290]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"26782","type":"Chemical","text":["CYP"],"offsets":[[1460,1463]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"26783","type":"Disease","text":["bladder inflammation"],"offsets":[[1656,1676]],"normalized":[{"db_name":"MESH","db_id":"D001745"}]},{"id":"26784","type":"Chemical","text":["CYP"],"offsets":[[1746,1749]],"normalized":[{"db_name":"MESH","db_id":"D003520"}]},{"id":"26785","type":"Disease","text":["bladder dysfunction"],"offsets":[[1801,1820]],"normalized":[{"db_name":"MESH","db_id":"D001745"}]},{"id":"26786","type":"Disease","text":["bladder inflammation"],"offsets":[[1843,1863]],"normalized":[{"db_name":"MESH","db_id":"D001745"}]}],"events":[],"coreferences":[],"relations":[{"id":"26787","type":"CID","arg1_id":"26768","arg2_id":"26770","normalized":[]},{"id":"26788","type":"CID","arg1_id":"26768","arg2_id":"26773","normalized":[]},{"id":"26789","type":"CID","arg1_id":"26768","arg2_id":"26774","normalized":[]},{"id":"26790","type":"CID","arg1_id":"26768","arg2_id":"26776","normalized":[]},{"id":"26791","type":"CID","arg1_id":"26769","arg2_id":"26770","normalized":[]},{"id":"26792","type":"CID","arg1_id":"26769","arg2_id":"26773","normalized":[]},{"id":"26793","type":"CID","arg1_id":"26769","arg2_id":"26774","normalized":[]},{"id":"26794","type":"CID","arg1_id":"26769","arg2_id":"26776","normalized":[]},{"id":"26795","type":"CID","arg1_id":"26771","arg2_id":"26770","normalized":[]},{"id":"26796","type":"CID","arg1_id":"26771","arg2_id":"26773","normalized":[]},{"id":"26797","type":"CID","arg1_id":"26771","arg2_id":"26774","normalized":[]},{"id":"26798","type":"CID","arg1_id":"26771","arg2_id":"26776","normalized":[]},{"id":"26799","type":"CID","arg1_id":"26772","arg2_id":"26770","normalized":[]},{"id":"26800","type":"CID","arg1_id":"26772","arg2_id":"26773","normalized":[]},{"id":"26801","type":"CID","arg1_id":"26772","arg2_id":"26774","normalized":[]},{"id":"26802","type":"CID","arg1_id":"26772","arg2_id":"26776","normalized":[]},{"id":"26803","type":"CID","arg1_id":"26775","arg2_id":"26770","normalized":[]},{"id":"26804","type":"CID","arg1_id":"26775","arg2_id":"26773","normalized":[]},{"id":"26805","type":"CID","arg1_id":"26775","arg2_id":"26774","normalized":[]},{"id":"26806","type":"CID","arg1_id":"26775","arg2_id":"26776","normalized":[]},{"id":"26807","type":"CID","arg1_id":"26777","arg2_id":"26770","normalized":[]},{"id":"26808","type":"CID","arg1_id":"26777","arg2_id":"26773","normalized":[]},{"id":"26809","type":"CID","arg1_id":"26777","arg2_id":"26774","normalized":[]},{"id":"26810","type":"CID","arg1_id":"26777","arg2_id":"26776","normalized":[]},{"id":"26811","type":"CID","arg1_id":"26778","arg2_id":"26770","normalized":[]},{"id":"26812","type":"CID","arg1_id":"26778","arg2_id":"26773","normalized":[]},{"id":"26813","type":"CID","arg1_id":"26778","arg2_id":"26774","normalized":[]},{"id":"26814","type":"CID","arg1_id":"26778","arg2_id":"26776","normalized":[]},{"id":"26815","type":"CID","arg1_id":"26779","arg2_id":"26770","normalized":[]},{"id":"26816","type":"CID","arg1_id":"26779","arg2_id":"26773","normalized":[]},{"id":"26817","type":"CID","arg1_id":"26779","arg2_id":"26774","normalized":[]},{"id":"26818","type":"CID","arg1_id":"26779","arg2_id":"26776","normalized":[]},{"id":"26819","type":"CID","arg1_id":"26780","arg2_id":"26770","normalized":[]},{"id":"26820","type":"CID","arg1_id":"26780","arg2_id":"26773","normalized":[]},{"id":"26821","type":"CID","arg1_id":"26780","arg2_id":"26774","normalized":[]},{"id":"26822","type":"CID","arg1_id":"26780","arg2_id":"26776","normalized":[]},{"id":"26823","type":"CID","arg1_id":"26781","arg2_id":"26770","normalized":[]},{"id":"26824","type":"CID","arg1_id":"26781","arg2_id":"26773","normalized":[]},{"id":"26825","type":"CID","arg1_id":"26781","arg2_id":"26774","normalized":[]},{"id":"26826","type":"CID","arg1_id":"26781","arg2_id":"26776","normalized":[]},{"id":"26827","type":"CID","arg1_id":"26782","arg2_id":"26770","normalized":[]},{"id":"26828","type":"CID","arg1_id":"26782","arg2_id":"26773","normalized":[]},{"id":"26829","type":"CID","arg1_id":"26782","arg2_id":"26774","normalized":[]},{"id":"26830","type":"CID","arg1_id":"26782","arg2_id":"26776","normalized":[]},{"id":"26831","type":"CID","arg1_id":"26784","arg2_id":"26770","normalized":[]},{"id":"26832","type":"CID","arg1_id":"26784","arg2_id":"26773","normalized":[]},{"id":"26833","type":"CID","arg1_id":"26784","arg2_id":"26774","normalized":[]},{"id":"26834","type":"CID","arg1_id":"26784","arg2_id":"26776","normalized":[]}]}
{"id":"26835","document_id":"17923537","passages":[{"id":"26836","type":"title","text":["Intraocular pressure in patients with uveitis treated with fluocinolone acetonide implants."],"offsets":[[0,91]]},{"id":"26837","type":"abstract","text":["OBJECTIVE: To report the incidence and management of elevated intraocular pressure (IOP) in patients with uveitis treated with the fluocinolone acetonide (FA) intravitreal implant. DESIGN: Pooled data from 3 multicenter, double-masked, randomized, controlled, phase 2b\/3 clinical trials evaluating the safety and efficacy of the 0.59-mg or 2.1-mg FA intravitreal implant or standard therapy were analyzed. RESULTS: During the 3-year follow-up, 71.0% of implanted eyes had an IOP increase of 10 mm Hg or more than baseline and 55.1%, 24.7%, and 6.2% of eyes reached an IOP of 30 mm Hg or more, 40 mm Hg or more, and 50 mm Hg or more, respectively. Topical IOP-lowering medication was administered in 74.8% of implanted eyes, and IOP-lowering surgeries, most of which were trabeculectomies (76.2%), were performed on 36.6% of implanted eyes. Intraocular pressure-lowering surgeries were considered a success (postoperative IOP of 6-21 mm Hg with or without additional IOP-lowering medication) in 85.1% of eyes at 1 year. The rate of hypotony (IOP <\/= 5 mm Hg) following IOP-lowering surgery (42.5%) was not different from that of implanted eyes not subjected to surgery (35.4%) (P = .09). CONCLUSION: Elevated IOP is a significant complication with the FA intravitreal implant but may be controlled with medication and surgery."],"offsets":[[92,1417]]}],"entities":[{"id":"26838","type":"Disease","text":["uveitis"],"offsets":[[38,45]],"normalized":[{"db_name":"MESH","db_id":"D014605"}]},{"id":"26839","type":"Chemical","text":["fluocinolone acetonide"],"offsets":[[59,81]],"normalized":[{"db_name":"MESH","db_id":"D005446"}]},{"id":"26840","type":"Disease","text":["elevated intraocular pressure"],"offsets":[[145,174]],"normalized":[{"db_name":"MESH","db_id":"D009798"}]},{"id":"26841","type":"Disease","text":["uveitis"],"offsets":[[198,205]],"normalized":[{"db_name":"MESH","db_id":"D014605"}]},{"id":"26842","type":"Chemical","text":["fluocinolone acetonide"],"offsets":[[223,245]],"normalized":[{"db_name":"MESH","db_id":"D005446"}]},{"id":"26843","type":"Chemical","text":["FA"],"offsets":[[247,249]],"normalized":[{"db_name":"MESH","db_id":"D005446"}]},{"id":"26844","type":"Chemical","text":["FA"],"offsets":[[439,441]],"normalized":[{"db_name":"MESH","db_id":"D005446"}]},{"id":"26845","type":"Disease","text":["hypotony"],"offsets":[[1123,1131]],"normalized":[{"db_name":"MESH","db_id":"D015814"}]}],"events":[],"coreferences":[],"relations":[{"id":"26846","type":"CID","arg1_id":"26839","arg2_id":"26840","normalized":[]},{"id":"26847","type":"CID","arg1_id":"26842","arg2_id":"26840","normalized":[]},{"id":"26848","type":"CID","arg1_id":"26843","arg2_id":"26840","normalized":[]},{"id":"26849","type":"CID","arg1_id":"26844","arg2_id":"26840","normalized":[]}]}
{"id":"26850","document_id":"15096016","passages":[{"id":"26851","type":"title","text":["Pallidal stimulation: an alternative to pallidotomy?"],"offsets":[[0,52]]},{"id":"26852","type":"abstract","text":["A resurgence of interest in the surgical treatment of Parkinson's disease (PD) came with the rediscovery of posteroventral pallidotomy by Laitinen in 1985. Laitinen's procedure improved most symptoms in drug-resistant PD, which engendered wide interest in the neurosurgical community. Another lesioning procedure, ventrolateral thalamotomy, has become a powerful alternative to stimulate the nucleus ventralis intermedius, producing high long-term success rates and low morbidity rates. Pallidal stimulation has not met with the same success. According to the literature pallidotomy improves the \"on\" symptoms of PD, such as dyskinesias, as well as the \"off\" symptoms, such as rigidity, bradykinesia, and on-off fluctuations. Pallidal stimulation improves bradykinesia and rigidity to a minor extent; however, its strength seems to be in improving levodopa-induced dyskinesias. Stimulation often produces an improvement in the hyper- or dyskinetic upper limbs, but increases the \"freezing\" phenomenon in the lower limbs at the same time. Considering the small increase in the patient's independence, the high costs of bilateral implants, and the difficulty most patients experience in handling the devices, the question arises as to whether bilateral pallidal stimulation is a real alternative to pallidotomy."],"offsets":[[53,1362]]}],"entities":[{"id":"26853","type":"Disease","text":["Parkinson's disease"],"offsets":[[107,126]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"26854","type":"Disease","text":["PD"],"offsets":[[128,130]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"26855","type":"Disease","text":["PD"],"offsets":[[271,273]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"26856","type":"Disease","text":["PD"],"offsets":[[666,668]],"normalized":[{"db_name":"MESH","db_id":"D010300"}]},{"id":"26857","type":"Disease","text":["dyskinesias"],"offsets":[[678,689]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"26858","type":"Disease","text":["rigidity"],"offsets":[[730,738]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"26859","type":"Disease","text":["bradykinesia"],"offsets":[[740,752]],"normalized":[{"db_name":"MESH","db_id":"D018476"}]},{"id":"26860","type":"Disease","text":["bradykinesia"],"offsets":[[809,821]],"normalized":[{"db_name":"MESH","db_id":"D018476"}]},{"id":"26861","type":"Disease","text":["rigidity"],"offsets":[[826,834]],"normalized":[{"db_name":"MESH","db_id":"D009127"}]},{"id":"26862","type":"Chemical","text":["levodopa"],"offsets":[[901,909]],"normalized":[{"db_name":"MESH","db_id":"D007980"}]},{"id":"26863","type":"Disease","text":["dyskinesias"],"offsets":[[918,929]],"normalized":[{"db_name":"MESH","db_id":"D004409"}]},{"id":"26864","type":"Disease","text":["hyper- or dyskinetic"],"offsets":[[980,1000]],"normalized":[{"db_name":"MESH","db_id":"D006948"},{"db_name":"MESH","db_id":"D004409"}]}],"events":[],"coreferences":[],"relations":[{"id":"26865","type":"CID","arg1_id":"26862","arg2_id":"26857","normalized":[]},{"id":"26866","type":"CID","arg1_id":"26862","arg2_id":"26863","normalized":[]},{"id":"26867","type":"CID","arg1_id":"26862","arg2_id":"26864","normalized":[]}]}
{"id":"26868","document_id":"12734532","passages":[{"id":"26869","type":"title","text":["Case report: Dexatrim (Phenylpropanolamine) as a cause of myocardial infarction."],"offsets":[[0,80]]},{"id":"26870","type":"abstract","text":["Phenylpropanolamine (PPA) is a sympathetic amine used in over-the-counter cold remedies and weight-control preparations worldwide. Its use has been associated with hypertensive episodes and hemorrhagic strokes in younger women. Several reports have linked the abuse of PPA with myocardial injury, especially when overdose is involved. We report here the first case of Dexatrim (PPA)-induced myocardial injury in a young woman who was using it at recommended doses for weight control. In addition, we review the 7 other cases of PPA related myocardial injury that have been reported so far. Physicians and patients should be alert to the potential cardiac risk associated with the use of PPA, even at doses generally considered to be safe."],"offsets":[[81,819]]}],"entities":[{"id":"26871","type":"Chemical","text":["Dexatrim"],"offsets":[[13,21]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"26872","type":"Chemical","text":["Phenylpropanolamine"],"offsets":[[23,42]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"26873","type":"Disease","text":["myocardial infarction"],"offsets":[[58,79]],"normalized":[{"db_name":"MESH","db_id":"D009203"}]},{"id":"26874","type":"Chemical","text":["Phenylpropanolamine"],"offsets":[[81,100]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"26875","type":"Chemical","text":["PPA"],"offsets":[[102,105]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"26876","type":"Chemical","text":["amine"],"offsets":[[124,129]],"normalized":[{"db_name":"MESH","db_id":"D000588"}]},{"id":"26877","type":"Disease","text":["hypertensive"],"offsets":[[245,257]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"26878","type":"Disease","text":["hemorrhagic strokes"],"offsets":[[271,290]],"normalized":[{"db_name":"MESH","db_id":"D006470"},{"db_name":"MESH","db_id":"D020521"}]},{"id":"26879","type":"Disease","text":["hemorrhagic"],"offsets":[[271,282]],"normalized":[{"db_name":"MESH","db_id":"D006470"}]},{"id":"26880","type":"Disease","text":["strokes"],"offsets":[[283,290]],"normalized":[{"db_name":"MESH","db_id":"D020521"}]},{"id":"26881","type":"Chemical","text":["PPA"],"offsets":[[350,353]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"26882","type":"Disease","text":["myocardial injury"],"offsets":[[359,376]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"26883","type":"Disease","text":["overdose"],"offsets":[[394,402]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"26884","type":"Chemical","text":["Dexatrim"],"offsets":[[449,457]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"26885","type":"Chemical","text":["PPA"],"offsets":[[459,462]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"26886","type":"Disease","text":["myocardial injury"],"offsets":[[472,489]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"26887","type":"Chemical","text":["PPA"],"offsets":[[609,612]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]},{"id":"26888","type":"Disease","text":["myocardial injury"],"offsets":[[621,638]],"normalized":[{"db_name":"MESH","db_id":"D009202"}]},{"id":"26889","type":"Chemical","text":["PPA"],"offsets":[[768,771]],"normalized":[{"db_name":"MESH","db_id":"D010665"}]}],"events":[],"coreferences":[],"relations":[{"id":"26890","type":"CID","arg1_id":"26871","arg2_id":"26873","normalized":[]},{"id":"26891","type":"CID","arg1_id":"26872","arg2_id":"26873","normalized":[]},{"id":"26892","type":"CID","arg1_id":"26874","arg2_id":"26873","normalized":[]},{"id":"26893","type":"CID","arg1_id":"26875","arg2_id":"26873","normalized":[]},{"id":"26894","type":"CID","arg1_id":"26881","arg2_id":"26873","normalized":[]},{"id":"26895","type":"CID","arg1_id":"26884","arg2_id":"26873","normalized":[]},{"id":"26896","type":"CID","arg1_id":"26885","arg2_id":"26873","normalized":[]},{"id":"26897","type":"CID","arg1_id":"26887","arg2_id":"26873","normalized":[]},{"id":"26898","type":"CID","arg1_id":"26889","arg2_id":"26873","normalized":[]}]}
{"id":"26899","document_id":"12013711","passages":[{"id":"26900","type":"title","text":["Risperidone-associated, benign transient visual disturbances in schizophrenic patients with a past history of LSD abuse."],"offsets":[[0,120]]},{"id":"26901","type":"abstract","text":["Two schizophrenic patients, who had a prior history of LSD abuse and who had previously developed EPS with classic antipsychotics, were successfully treated with risperidone. They both reported short episodes of transient visual disturbances, which appeared immediately after starting treatment with risperidone. This imagery resembled visual disturbances previously experienced as \"flashbacks\" related to prior LSD consumption. Risperidone administration was continued and the visual disturbances gradually wore off. During a six-month follow-up period, there was no recurrence of visual disturbances. This phenomenon may be interpreted as a benign, short-term and self-limiting side effect which does not contraindicate the use of risperidone or interfere with treatment. Conclusions based on two case reports should be taken with appropriate caution."],"offsets":[[121,974]]}],"entities":[{"id":"26902","type":"Chemical","text":["Risperidone"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"26903","type":"Disease","text":["visual disturbances"],"offsets":[[41,60]],"normalized":[{"db_name":"MESH","db_id":"D010468"}]},{"id":"26904","type":"Disease","text":["schizophrenic"],"offsets":[[64,77]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"26905","type":"Chemical","text":["LSD"],"offsets":[[110,113]],"normalized":[{"db_name":"MESH","db_id":"D008238"}]},{"id":"26906","type":"Disease","text":["schizophrenic"],"offsets":[[125,138]],"normalized":[{"db_name":"MESH","db_id":"D012559"}]},{"id":"26907","type":"Chemical","text":["LSD"],"offsets":[[176,179]],"normalized":[{"db_name":"MESH","db_id":"D008238"}]},{"id":"26908","type":"Disease","text":["EPS"],"offsets":[[219,222]],"normalized":[{"db_name":"MESH","db_id":"D001480"}]},{"id":"26909","type":"Chemical","text":["risperidone"],"offsets":[[283,294]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"26910","type":"Disease","text":["visual disturbances"],"offsets":[[343,362]],"normalized":[{"db_name":"MESH","db_id":"D010468"}]},{"id":"26911","type":"Chemical","text":["risperidone"],"offsets":[[421,432]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"26912","type":"Disease","text":["visual disturbances"],"offsets":[[457,476]],"normalized":[{"db_name":"MESH","db_id":"D010468"}]},{"id":"26913","type":"Chemical","text":["LSD"],"offsets":[[533,536]],"normalized":[{"db_name":"MESH","db_id":"D008238"}]},{"id":"26914","type":"Chemical","text":["Risperidone"],"offsets":[[550,561]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]},{"id":"26915","type":"Disease","text":["visual disturbances"],"offsets":[[599,618]],"normalized":[{"db_name":"MESH","db_id":"D010468"}]},{"id":"26916","type":"Disease","text":["visual disturbances"],"offsets":[[703,722]],"normalized":[{"db_name":"MESH","db_id":"D010468"}]},{"id":"26917","type":"Chemical","text":["risperidone"],"offsets":[[854,865]],"normalized":[{"db_name":"MESH","db_id":"D018967"}]}],"events":[],"coreferences":[],"relations":[{"id":"26918","type":"CID","arg1_id":"26902","arg2_id":"26903","normalized":[]},{"id":"26919","type":"CID","arg1_id":"26902","arg2_id":"26910","normalized":[]},{"id":"26920","type":"CID","arg1_id":"26902","arg2_id":"26912","normalized":[]},{"id":"26921","type":"CID","arg1_id":"26902","arg2_id":"26915","normalized":[]},{"id":"26922","type":"CID","arg1_id":"26902","arg2_id":"26916","normalized":[]},{"id":"26923","type":"CID","arg1_id":"26909","arg2_id":"26903","normalized":[]},{"id":"26924","type":"CID","arg1_id":"26909","arg2_id":"26910","normalized":[]},{"id":"26925","type":"CID","arg1_id":"26909","arg2_id":"26912","normalized":[]},{"id":"26926","type":"CID","arg1_id":"26909","arg2_id":"26915","normalized":[]},{"id":"26927","type":"CID","arg1_id":"26909","arg2_id":"26916","normalized":[]},{"id":"26928","type":"CID","arg1_id":"26911","arg2_id":"26903","normalized":[]},{"id":"26929","type":"CID","arg1_id":"26911","arg2_id":"26910","normalized":[]},{"id":"26930","type":"CID","arg1_id":"26911","arg2_id":"26912","normalized":[]},{"id":"26931","type":"CID","arg1_id":"26911","arg2_id":"26915","normalized":[]},{"id":"26932","type":"CID","arg1_id":"26911","arg2_id":"26916","normalized":[]},{"id":"26933","type":"CID","arg1_id":"26914","arg2_id":"26903","normalized":[]},{"id":"26934","type":"CID","arg1_id":"26914","arg2_id":"26910","normalized":[]},{"id":"26935","type":"CID","arg1_id":"26914","arg2_id":"26912","normalized":[]},{"id":"26936","type":"CID","arg1_id":"26914","arg2_id":"26915","normalized":[]},{"id":"26937","type":"CID","arg1_id":"26914","arg2_id":"26916","normalized":[]},{"id":"26938","type":"CID","arg1_id":"26917","arg2_id":"26903","normalized":[]},{"id":"26939","type":"CID","arg1_id":"26917","arg2_id":"26910","normalized":[]},{"id":"26940","type":"CID","arg1_id":"26917","arg2_id":"26912","normalized":[]},{"id":"26941","type":"CID","arg1_id":"26917","arg2_id":"26915","normalized":[]},{"id":"26942","type":"CID","arg1_id":"26917","arg2_id":"26916","normalized":[]}]}
{"id":"26943","document_id":"11861791","passages":[{"id":"26944","type":"title","text":["Activation of poly(ADP-ribose) polymerase contributes to development of doxorubicin-induced heart failure."],"offsets":[[0,106]]},{"id":"26945","type":"abstract","text":["Activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) by oxidant-mediated DNA damage is an important pathway of cell dysfunction and tissue injury in conditions associated with oxidative stress. Increased oxidative stress is a major factor implicated in the cardiotoxicity of doxorubicin (DOX), a widely used antitumor anthracycline antibiotic. Thus, we hypothesized that the activation of PARP may contribute to the DOX-induced cardiotoxicity. Using a dual approach of PARP-1 suppression, by genetic deletion or pharmacological inhibition with the phenanthridinone PARP inhibitor PJ34, we now demonstrate the role of PARP in the development of cardiac dysfunction induced by DOX. PARP-1+\/+ and PARP-1-\/- mice received a single injection of DOX (25 mg\/kg i.p). Five days after DOX administration, left ventricular performance was significantly depressed in PARP-1+\/+ mice, but only to a smaller extent in PARP-1-\/- ones. Similar experiments were conducted in BALB\/c mice treated with PJ34 or vehicle. Treatment with a PJ34 significantly improved cardiac dysfunction and increased the survival of the animals. In addition PJ34 significantly reduced the DOX-induced increase in the serum lactate dehydrogenase and creatine kinase activities but not metalloproteinase activation in the heart. Thus, PARP activation contributes to the cardiotoxicity of DOX. PARP inhibitors may exert protective effects against the development of severe cardiac complications associated with the DOX treatment."],"offsets":[[107,1610]]}],"entities":[{"id":"26946","type":"Chemical","text":["poly(ADP-ribose)"],"offsets":[[14,30]],"normalized":[{"db_name":"MESH","db_id":"D011064"}]},{"id":"26947","type":"Chemical","text":["doxorubicin"],"offsets":[[72,83]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"26948","type":"Disease","text":["heart failure"],"offsets":[[92,105]],"normalized":[{"db_name":"MESH","db_id":"D006333"}]},{"id":"26949","type":"Chemical","text":["poly(ADP-ribose)"],"offsets":[[140,156]],"normalized":[{"db_name":"MESH","db_id":"D011064"}]},{"id":"26950","type":"Disease","text":["cardiotoxicity"],"offsets":[[379,393]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"26951","type":"Chemical","text":["doxorubicin"],"offsets":[[397,408]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"26952","type":"Chemical","text":["DOX"],"offsets":[[410,413]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"26953","type":"Chemical","text":["anthracycline"],"offsets":[[440,453]],"normalized":[{"db_name":"MESH","db_id":"D018943"}]},{"id":"26954","type":"Chemical","text":["DOX"],"offsets":[[538,541]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"26955","type":"Disease","text":["cardiotoxicity"],"offsets":[[550,564]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"26956","type":"Chemical","text":["PJ34"],"offsets":[[702,706]],"normalized":[{"db_name":"MESH","db_id":"C434926"}]},{"id":"26957","type":"Disease","text":["cardiac dysfunction"],"offsets":[[766,785]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"26958","type":"Chemical","text":["DOX"],"offsets":[[797,800]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"26959","type":"Chemical","text":["DOX"],"offsets":[[862,865]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"26960","type":"Chemical","text":["DOX"],"offsets":[[898,901]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"26961","type":"Chemical","text":["PJ34"],"offsets":[[1105,1109]],"normalized":[{"db_name":"MESH","db_id":"C434926"}]},{"id":"26962","type":"Chemical","text":["PJ34"],"offsets":[[1139,1143]],"normalized":[{"db_name":"MESH","db_id":"C434926"}]},{"id":"26963","type":"Disease","text":["cardiac dysfunction"],"offsets":[[1167,1186]],"normalized":[{"db_name":"MESH","db_id":"D006331"}]},{"id":"26964","type":"Chemical","text":["PJ34"],"offsets":[[1242,1246]],"normalized":[{"db_name":"MESH","db_id":"C434926"}]},{"id":"26965","type":"Chemical","text":["DOX"],"offsets":[[1273,1276]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"26966","type":"Chemical","text":["lactate"],"offsets":[[1307,1314]],"normalized":[{"db_name":"MESH","db_id":"D019344"}]},{"id":"26967","type":"Chemical","text":["creatine"],"offsets":[[1333,1341]],"normalized":[{"db_name":"MESH","db_id":"D003401"}]},{"id":"26968","type":"Disease","text":["cardiotoxicity"],"offsets":[[1452,1466]],"normalized":[{"db_name":"MESH","db_id":"D066126"}]},{"id":"26969","type":"Chemical","text":["DOX"],"offsets":[[1470,1473]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]},{"id":"26970","type":"Disease","text":["cardiac complications"],"offsets":[[1554,1575]],"normalized":[{"db_name":"MESH","db_id":"D005117"}]},{"id":"26971","type":"Chemical","text":["DOX"],"offsets":[[1596,1599]],"normalized":[{"db_name":"MESH","db_id":"D004317"}]}],"events":[],"coreferences":[],"relations":[{"id":"26972","type":"CID","arg1_id":"26947","arg2_id":"26948","normalized":[]},{"id":"26973","type":"CID","arg1_id":"26951","arg2_id":"26948","normalized":[]},{"id":"26974","type":"CID","arg1_id":"26952","arg2_id":"26948","normalized":[]},{"id":"26975","type":"CID","arg1_id":"26954","arg2_id":"26948","normalized":[]},{"id":"26976","type":"CID","arg1_id":"26958","arg2_id":"26948","normalized":[]},{"id":"26977","type":"CID","arg1_id":"26959","arg2_id":"26948","normalized":[]},{"id":"26978","type":"CID","arg1_id":"26960","arg2_id":"26948","normalized":[]},{"id":"26979","type":"CID","arg1_id":"26965","arg2_id":"26948","normalized":[]},{"id":"26980","type":"CID","arg1_id":"26969","arg2_id":"26948","normalized":[]},{"id":"26981","type":"CID","arg1_id":"26971","arg2_id":"26948","normalized":[]}]}
{"id":"26982","document_id":"11302406","passages":[{"id":"26983","type":"title","text":["Fluconazole-induced torsade de pointes."],"offsets":[[0,39]]},{"id":"26984","type":"abstract","text":["OBJECTIVE: To present a case of fluconazole-associated torsade de pointes (TDP) and discuss fluconazole's role in causing TDP. CASE SUMMARY: A 68-year-old white woman with Candida glabrata isolated from a presacral abscess developed TDP eight days after commencing oral fluconazole The patient had no other risk factors for TDP, including coronary artery disease, cardiomyopathy, congestive heart failure, and electrolyte abnormalities There was a temporal association between the initiation of fluconazole and TDP. The TDP resolved when fluconazole was discontinued; however, the patient continued to have premature ventricular contractions and nonsustained ventricular tachycardia (NSVT) until six days after drug cessation DISCUSSION: Use of the Naranjo probability scale indicates a probable relationship between the use of fluconazole and the development of TDP. The possible mechanism is depression of rapidly activating delayed rectifier potassium currents. In our patient, there was no other etiology identified that could explain QT prolongation or TDP The complete disappearance of NSVT and premature ventricular contractions followed by normalization of QT interval after the drug was stopped strongly suggests fluconazole as the etiology. CONCLUSIONS: Clinicians should be aware that fluconazole, even at low doses, may cause prolongation of the QT interval, leading to TDP. Serial electrocardiographic monitoring may be considered when fluconazole is administered in patients who are at risk for ventricular arrhythmias."],"offsets":[[40,1573]]}],"entities":[{"id":"26985","type":"Chemical","text":["Fluconazole"],"offsets":[[0,11]],"normalized":[{"db_name":"MESH","db_id":"D015725"}]},{"id":"26986","type":"Disease","text":["torsade de pointes"],"offsets":[[20,38]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"26987","type":"Chemical","text":["fluconazole"],"offsets":[[72,83]],"normalized":[{"db_name":"MESH","db_id":"D015725"}]},{"id":"26988","type":"Disease","text":["torsade de 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{"id":"27129","document_id":"11058428","passages":[{"id":"27130","type":"title","text":["High-dose methylprednisolone may do more harm for spinal cord injury."],"offsets":[[0,69]]},{"id":"27131","type":"abstract","text":["Because of the National Acute Spinal Cord Injury Studies (NASCIS), high-dose methylprednisolone became the standard of care for the acute spinal cord injury. In the NASCIS, there was no mention regarding the possibility of acute corticosteroid myopathy that high-dose methylprednisolone may cause. The dosage of methylprednisolone recommended by the NASCIS 3 is the highest dose of steroids ever being used during a 2-day period for any clinical condition. We hypothesize that it may cause some damage to the muscle of spinal cord injury patients. Further, steroid myopathy recovers naturally and the neurological improvement shown in the NASCIS may be just a recording of this natural motor recovery from the steroid myopathy, instead of any protection that methylprednisolone offers to the spinal cord injury. To our knowledge, this is the first discussion considering the possibility that the methylprednisolone recommended by NASCIS may cause acute corticosteroid myopathy."],"offsets":[[70,1047]]}],"entities":[{"id":"27132","type":"Chemical","text":["methylprednisolone"],"offsets":[[10,28]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"27133","type":"Disease","text":["spinal cord injury"],"offsets":[[50,68]],"normalized":[{"db_name":"MESH","db_id":"D013119"}]},{"id":"27134","type":"Disease","text":["Spinal Cord Injury"],"offsets":[[100,118]],"normalized":[{"db_name":"MESH","db_id":"D013119"}]},{"id":"27135","type":"Chemical","text":["methylprednisolone"],"offsets":[[147,165]],"normalized":[{"db_name":"MESH","db_id":"D008775"}]},{"id":"27136","type":"Disease","text":["spinal cord 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{"id":"27183","document_id":"11022397","passages":[{"id":"27184","type":"title","text":["Probing peripheral and central cholinergic system responses."],"offsets":[[0,60]]},{"id":"27185","type":"abstract","text":["OBJECTIVE: The pharmacological response to drugs that act on the cholinergic system of the iris has been used to predict deficits in central cholinergic functioning due to diseases such as Alzheimer's disease, yet correlations between central and peripheral responses have not been properly studied. This study assessed the effect of normal aging on (1) the tropicamide-induced increase in pupil diameter, and (2) the reversal of this effect with pilocarpine. Scopolamine was used as a positive control to detect age-dependent changes in central cholinergic functioning in the elderly. DESIGN: Randomized double-blind controlled trial. PARTICIPANTS: Ten healthy elderly (mean age 70) and 9 young (mean age 33) volunteers. INTERVENTIONS: Pupil diameter was monitored using a computerized infrared pupillometer over 4 hours. The study involved 4 sessions. In 1 session, tropicamide (20 microL, 0.01%) was administered to one eye and placebo to the other. In another session, tropicamide (20 microL, 0.01%) was administered to both eyes, followed 23 minutes later by the application of pilocarpine (20 microL, 0.1%) to one eye and placebo to the other. All eye drops were given in a randomized order. In 2 separate sessions, a single dose of scopolamine (0.5 mg, intravenously) or placebo was administered, and the effects on word recall were measured using the Buschke Selective Reminding Test over 2 hours. OUTCOME MEASURES: Pupil size at time points after administration of tropicamide and pilocarpine; scopolamine-induced impairment in word recall. RESULTS: There was no significant difference between elderly and young volunteers in pupillary response to tropicamide at any time point (p > 0.05). The elderly group had a significantly greater pilocarpine-induced net decrease in pupil size 85, 125, 165 and 215 minutes after administration, compared with the young group (p < 0.05). Compared with the young group, the elderly group had greater scopolamine-induced impairment in word recall 60, 90 and 120 minutes after administration (p < 0.05). CONCLUSION: There is an age-related pupillary response to pilocarpine that is not found with tropicamide. Thus, pilocarpine may be useful to assess variations in central cholinergic function in elderly patients."],"offsets":[[61,2320]]}],"entities":[{"id":"27186","type":"Disease","text":["Alzheimer's disease"],"offsets":[[250,269]],"normalized":[{"db_name":"MESH","db_id":"D000544"}]},{"id":"27187","type":"Chemical","text":["tropicamide"],"offsets":[[419,430]],"normalized":[{"db_name":"MESH","db_id":"D014331"}]},{"id":"27188","type":"Chemical","text":["pilocarpine"],"offsets":[[508,519]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"27189","type":"Chemical","text":["Scopolamine"],"offsets":[[521,532]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"27190","type":"Chemical","text":["tropicamide"],"offsets":[[929,940]],"normalized":[{"db_name":"MESH","db_id":"D014331"}]},{"id":"27191","type":"Chemical","text":["tropicamide"],"offsets":[[1034,1045]],"normalized":[{"db_name":"MESH","db_id":"D014331"}]},{"id":"27192","type":"Chemical","text":["pilocarpine"],"offsets":[[1144,1155]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"27193","type":"Chemical","text":["scopolamine"],"offsets":[[1300,1311]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"27194","type":"Chemical","text":["tropicamide"],"offsets":[[1535,1546]],"normalized":[{"db_name":"MESH","db_id":"D014331"}]},{"id":"27195","type":"Chemical","text":["pilocarpine"],"offsets":[[1551,1562]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"27196","type":"Chemical","text":["scopolamine"],"offsets":[[1564,1575]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"27197","type":"Disease","text":["impairment in word recall"],"offsets":[[1584,1609]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"27198","type":"Chemical","text":["tropicamide"],"offsets":[[1718,1729]],"normalized":[{"db_name":"MESH","db_id":"D014331"}]},{"id":"27199","type":"Chemical","text":["pilocarpine"],"offsets":[[1806,1817]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"27200","type":"Chemical","text":["scopolamine"],"offsets":[[2007,2018]],"normalized":[{"db_name":"MESH","db_id":"D012601"}]},{"id":"27201","type":"Disease","text":["impairment in word recall"],"offsets":[[2027,2052]],"normalized":[{"db_name":"MESH","db_id":"D008569"}]},{"id":"27202","type":"Chemical","text":["pilocarpine"],"offsets":[[2167,2178]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]},{"id":"27203","type":"Chemical","text":["tropicamide"],"offsets":[[2202,2213]],"normalized":[{"db_name":"MESH","db_id":"D014331"}]},{"id":"27204","type":"Chemical","text":["pilocarpine"],"offsets":[[2221,2232]],"normalized":[{"db_name":"MESH","db_id":"D010862"}]}],"events":[],"coreferences":[],"relations":[{"id":"27205","type":"CID","arg1_id":"27189","arg2_id":"27197","normalized":[]},{"id":"27206","type":"CID","arg1_id":"27189","arg2_id":"27201","normalized":[]},{"id":"27207","type":"CID","arg1_id":"27193","arg2_id":"27197","normalized":[]},{"id":"27208","type":"CID","arg1_id":"27193","arg2_id":"27201","normalized":[]},{"id":"27209","type":"CID","arg1_id":"27196","arg2_id":"27197","normalized":[]},{"id":"27210","type":"CID","arg1_id":"27196","arg2_id":"27201","normalized":[]},{"id":"27211","type":"CID","arg1_id":"27200","arg2_id":"27197","normalized":[]},{"id":"27212","type":"CID","arg1_id":"27200","arg2_id":"27201","normalized":[]}]}
{"id":"27213","document_id":"10692744","passages":[{"id":"27214","type":"title","text":["Acetazolamide-induced Gerstmann syndrome."],"offsets":[[0,41]]},{"id":"27215","type":"abstract","text":["Acute confusion induced by acetazolamide is a well known adverse drug reaction in patients with renal impairment. We report a case of acetazolamide-induced Gerstmann syndrome in a patient with normal renal function, to highlight predisposing factors that are frequently overlooked."],"offsets":[[42,323]]}],"entities":[{"id":"27216","type":"Chemical","text":["Acetazolamide"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D000086"}]},{"id":"27217","type":"Disease","text":["Gerstmann syndrome"],"offsets":[[22,40]],"normalized":[{"db_name":"MESH","db_id":"D005862"}]},{"id":"27218","type":"Disease","text":["confusion"],"offsets":[[48,57]],"normalized":[{"db_name":"MESH","db_id":"D003221"}]},{"id":"27219","type":"Chemical","text":["acetazolamide"],"offsets":[[69,82]],"normalized":[{"db_name":"MESH","db_id":"D000086"}]},{"id":"27220","type":"Disease","text":["renal impairment"],"offsets":[[138,154]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"27221","type":"Chemical","text":["acetazolamide"],"offsets":[[176,189]],"normalized":[{"db_name":"MESH","db_id":"D000086"}]},{"id":"27222","type":"Disease","text":["Gerstmann syndrome"],"offsets":[[198,216]],"normalized":[{"db_name":"MESH","db_id":"D005862"}]}],"events":[],"coreferences":[],"relations":[{"id":"27223","type":"CID","arg1_id":"27216","arg2_id":"27217","normalized":[]},{"id":"27224","type":"CID","arg1_id":"27216","arg2_id":"27222","normalized":[]},{"id":"27225","type":"CID","arg1_id":"27219","arg2_id":"27217","normalized":[]},{"id":"27226","type":"CID","arg1_id":"27219","arg2_id":"27222","normalized":[]},{"id":"27227","type":"CID","arg1_id":"27221","arg2_id":"27217","normalized":[]},{"id":"27228","type":"CID","arg1_id":"27221","arg2_id":"27222","normalized":[]}]}
{"id":"27229","document_id":"10565806","passages":[{"id":"27230","type":"title","text":["Hypomania-like syndrome induced by olanzapine."],"offsets":[[0,46]]},{"id":"27231","type":"abstract","text":["We report a female patient with a diagnosis of a not otherwise specified psychotic disorder (DSM-IV) who developed hypomania shortly after the introduction of olanzapine treatment."],"offsets":[[47,227]]}],"entities":[{"id":"27232","type":"Disease","text":["Hypomania"],"offsets":[[0,9]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"27233","type":"Chemical","text":["olanzapine"],"offsets":[[35,45]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]},{"id":"27234","type":"Disease","text":["psychotic disorder"],"offsets":[[120,138]],"normalized":[{"db_name":"MESH","db_id":"D011618"}]},{"id":"27235","type":"Disease","text":["hypomania"],"offsets":[[162,171]],"normalized":[{"db_name":"MESH","db_id":"D001714"}]},{"id":"27236","type":"Chemical","text":["olanzapine"],"offsets":[[206,216]],"normalized":[{"db_name":"MESH","db_id":"C076029"}]}],"events":[],"coreferences":[],"relations":[{"id":"27237","type":"CID","arg1_id":"27233","arg2_id":"27232","normalized":[]},{"id":"27238","type":"CID","arg1_id":"27233","arg2_id":"27235","normalized":[]},{"id":"27239","type":"CID","arg1_id":"27236","arg2_id":"27232","normalized":[]},{"id":"27240","type":"CID","arg1_id":"27236","arg2_id":"27235","normalized":[]}]}
{"id":"27241","document_id":"9061311","passages":[{"id":"27242","type":"title","text":["Neutrophil superoxide and hydrogen peroxide production in patients with acute liver failure."],"offsets":[[0,92]]},{"id":"27243","type":"abstract","text":["Defects in superoxide and hydrogen peroxide production may be implicated in the high incidence of bacterial infections in patients with acute liver failure (ALF). In the present study, oxygen radical production in patients with ALF due to paracetamol overdose was compared with that of healthy volunteers. Neutrophils from 14 ALF patients were stimulated via the complement receptors using zymosan opsonized with ALF or control serum. Superoxide and hydrogen peroxide production by ALF neutrophils stimulated with zymosan opsonized with ALF serum was significantly reduced compared with the control subjects (P < 0.01). This defect persisted when zymosan opsonized by control serum was used (P < 0.05). Superoxide and hydrogen peroxide production in neutrophils stimulated with formyl-methionyl-leucyl-phenylalanine (fMLP) from a further 18 ALF patients was unaffected compared with control neutrophils. Serum C3 complement levels were significantly reduced in ALF patients compared with control subjects (P < 0.0005). These results demonstrate a neutrophil defect in ALF due to paracetamol overdose, that is complement dependent but independent of serum complement, possibly connected to the complement receptor."],"offsets":[[93,1306]]}],"entities":[{"id":"27244","type":"Chemical","text":["superoxide"],"offsets":[[11,21]],"normalized":[{"db_name":"MESH","db_id":"D013481"}]},{"id":"27245","type":"Chemical","text":["hydrogen peroxide"],"offsets":[[26,43]],"normalized":[{"db_name":"MESH","db_id":"D006861"}]},{"id":"27246","type":"Disease","text":["acute liver failure"],"offsets":[[72,91]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"27247","type":"Chemical","text":["superoxide"],"offsets":[[104,114]],"normalized":[{"db_name":"MESH","db_id":"D013481"}]},{"id":"27248","type":"Chemical","text":["hydrogen peroxide"],"offsets":[[119,136]],"normalized":[{"db_name":"MESH","db_id":"D006861"}]},{"id":"27249","type":"Disease","text":["bacterial infections"],"offsets":[[191,211]],"normalized":[{"db_name":"MESH","db_id":"D001424"}]},{"id":"27250","type":"Disease","text":["acute liver failure"],"offsets":[[229,248]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"27251","type":"Disease","text":["ALF"],"offsets":[[250,253]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"27252","type":"Chemical","text":["oxygen"],"offsets":[[278,284]],"normalized":[{"db_name":"MESH","db_id":"D010100"}]},{"id":"27253","type":"Disease","text":["ALF"],"offsets":[[321,324]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"27254","type":"Chemical","text":["paracetamol"],"offsets":[[332,343]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"27255","type":"Disease","text":["overdose"],"offsets":[[344,352]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]},{"id":"27256","type":"Disease","text":["ALF"],"offsets":[[419,422]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"27257","type":"Disease","text":["ALF"],"offsets":[[506,509]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"27258","type":"Chemical","text":["Superoxide"],"offsets":[[528,538]],"normalized":[{"db_name":"MESH","db_id":"D013481"}]},{"id":"27259","type":"Chemical","text":["hydrogen peroxide"],"offsets":[[543,560]],"normalized":[{"db_name":"MESH","db_id":"D006861"}]},{"id":"27260","type":"Disease","text":["ALF"],"offsets":[[575,578]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"27261","type":"Disease","text":["ALF"],"offsets":[[630,633]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"27262","type":"Chemical","text":["Superoxide"],"offsets":[[796,806]],"normalized":[{"db_name":"MESH","db_id":"D013481"}]},{"id":"27263","type":"Chemical","text":["hydrogen peroxide"],"offsets":[[811,828]],"normalized":[{"db_name":"MESH","db_id":"D006861"}]},{"id":"27264","type":"Chemical","text":["formyl-methionyl-leucyl-phenylalanine"],"offsets":[[871,908]],"normalized":[{"db_name":"MESH","db_id":"D009240"}]},{"id":"27265","type":"Chemical","text":["fMLP"],"offsets":[[910,914]],"normalized":[{"db_name":"MESH","db_id":"D009240"}]},{"id":"27266","type":"Disease","text":["ALF"],"offsets":[[934,937]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"27267","type":"Disease","text":["ALF"],"offsets":[[1054,1057]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"27268","type":"Disease","text":["ALF"],"offsets":[[1161,1164]],"normalized":[{"db_name":"MESH","db_id":"D017114"}]},{"id":"27269","type":"Chemical","text":["paracetamol"],"offsets":[[1172,1183]],"normalized":[{"db_name":"MESH","db_id":"D000082"}]},{"id":"27270","type":"Disease","text":["overdose"],"offsets":[[1184,1192]],"normalized":[{"db_name":"MESH","db_id":"D062787"}]}],"events":[],"coreferences":[],"relations":[{"id":"27271","type":"CID","arg1_id":"27254","arg2_id":"27246","normalized":[]},{"id":"27272","type":"CID","arg1_id":"27254","arg2_id":"27250","normalized":[]},{"id":"27273","type":"CID","arg1_id":"27254","arg2_id":"27251","normalized":[]},{"id":"27274","type":"CID","arg1_id":"27254","arg2_id":"27253","normalized":[]},{"id":"27275","type":"CID","arg1_id":"27254","arg2_id":"27256","normalized":[]},{"id":"27276","type":"CID","arg1_id":"27254","arg2_id":"27257","normalized":[]},{"id":"27277","type":"CID","arg1_id":"27254","arg2_id":"27260","normalized":[]},{"id":"27278","type":"CID","arg1_id":"27254","arg2_id":"27261","normalized":[]},{"id":"27279","type":"CID","arg1_id":"27254","arg2_id":"27266","normalized":[]},{"id":"27280","type":"CID","arg1_id":"27254","arg2_id":"27267","normalized":[]},{"id":"27281","type":"CID","arg1_id":"27254","arg2_id":"27268","normalized":[]},{"id":"27282","type":"CID","arg1_id":"27269","arg2_id":"27246","normalized":[]},{"id":"27283","type":"CID","arg1_id":"27269","arg2_id":"27250","normalized":[]},{"id":"27284","type":"CID","arg1_id":"27269","arg2_id":"27251","normalized":[]},{"id":"27285","type":"CID","arg1_id":"27269","arg2_id":"27253","normalized":[]},{"id":"27286","type":"CID","arg1_id":"27269","arg2_id":"27256","normalized":[]},{"id":"27287","type":"CID","arg1_id":"27269","arg2_id":"27257","normalized":[]},{"id":"27288","type":"CID","arg1_id":"27269","arg2_id":"27260","normalized":[]},{"id":"27289","type":"CID","arg1_id":"27269","arg2_id":"27261","normalized":[]},{"id":"27290","type":"CID","arg1_id":"27269","arg2_id":"27266","normalized":[]},{"id":"27291","type":"CID","arg1_id":"27269","arg2_id":"27267","normalized":[]},{"id":"27292","type":"CID","arg1_id":"27269","arg2_id":"27268","normalized":[]}]}
{"id":"27293","document_id":"8617710","passages":[{"id":"27294","type":"title","text":["Absence of effect of sertraline on time-based sensitization of cognitive impairment with haloperidol."],"offsets":[[0,101]]},{"id":"27295","type":"abstract","text":["This double-blind, randomized, placebo-controlled study evaluated the effects of haloperidol alone and haloperidol plus sertraline on cognitive and psychomotor function in 24 healthy male subjects. METHOD: All subjects received placebo on Day 1 and haloperidol 2 mg on Days 2 and 25. From Days 9 to 25, subjects were randomly assigned to either sertraline (12 subjects) or placebo (12 subjects); the sertraline dose was titrated from 50 to 200 mg\/day from Days 9 to 16, and remained at 200 mg\/day for the final 10 days of the drug administration period. Cognitive function testing was performed before dosing and over a 24-hour period after dosing on Days 1, 2, and 25. RESULTS: Impairment of cognitive function was observed 6 to 8 hours after administration of haloperidol on Day 2 but was not evident 23 hours after dosing. When single-dose haloperidol was given again 25 days later, greater impairment with earlier onset was noted in several tests in both treatment groups, suggesting enhancement of this effect. There was no indication that sertraline exacerbated the impairment produced by haloperidol since an equivalent effect also occurred in the placebo group. Three subjects (2 on sertraline and 1 on placebo) withdrew from the study because of side effects. Ten subjects in each group reported side effects related to treatment. The side effect profiles of sertraline and of placebo were similar. CONCLUSION: Haloperidol produced a clear profile of cognitive impairment that was not worsened by concomitant sertraline administration."],"offsets":[[102,1646]]}],"entities":[{"id":"27296","type":"Chemical","text":["sertraline"],"offsets":[[21,31]],"normalized":[{"db_name":"MESH","db_id":"D020280"}]},{"id":"27297","type":"Disease","text":["cognitive impairment"],"offsets":[[63,83]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"27298","type":"Chemical","text":["haloperidol"],"offsets":[[89,100]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"27299","type":"Chemical","text":["haloperidol"],"offsets":[[183,194]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"27300","type":"Chemical","text":["haloperidol"],"offsets":[[205,216]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"27301","type":"Chemical","text":["sertraline"],"offsets":[[222,232]],"normalized":[{"db_name":"MESH","db_id":"D020280"}]},{"id":"27302","type":"Chemical","text":["haloperidol"],"offsets":[[351,362]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"27303","type":"Chemical","text":["sertraline"],"offsets":[[447,457]],"normalized":[{"db_name":"MESH","db_id":"D020280"}]},{"id":"27304","type":"Chemical","text":["sertraline"],"offsets":[[502,512]],"normalized":[{"db_name":"MESH","db_id":"D020280"}]},{"id":"27305","type":"Disease","text":["Impairment of cognitive function"],"offsets":[[781,813]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"27306","type":"Chemical","text":["haloperidol"],"offsets":[[864,875]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"27307","type":"Chemical","text":["haloperidol"],"offsets":[[945,956]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"27308","type":"Chemical","text":["sertraline"],"offsets":[[1147,1157]],"normalized":[{"db_name":"MESH","db_id":"D020280"}]},{"id":"27309","type":"Chemical","text":["haloperidol"],"offsets":[[1197,1208]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"27310","type":"Chemical","text":["sertraline"],"offsets":[[1293,1303]],"normalized":[{"db_name":"MESH","db_id":"D020280"}]},{"id":"27311","type":"Chemical","text":["sertraline"],"offsets":[[1470,1480]],"normalized":[{"db_name":"MESH","db_id":"D020280"}]},{"id":"27312","type":"Chemical","text":["Haloperidol"],"offsets":[[1522,1533]],"normalized":[{"db_name":"MESH","db_id":"D006220"}]},{"id":"27313","type":"Disease","text":["cognitive impairment"],"offsets":[[1562,1582]],"normalized":[{"db_name":"MESH","db_id":"D003072"}]},{"id":"27314","type":"Chemical","text":["sertraline"],"offsets":[[1620,1630]],"normalized":[{"db_name":"MESH","db_id":"D020280"}]}],"events":[],"coreferences":[],"relations":[{"id":"27315","type":"CID","arg1_id":"27298","arg2_id":"27297","normalized":[]},{"id":"27316","type":"CID","arg1_id":"27298","arg2_id":"27305","normalized":[]},{"id":"27317","type":"CID","arg1_id":"27298","arg2_id":"27313","normalized":[]},{"id":"27318","type":"CID","arg1_id":"27299","arg2_id":"27297","normalized":[]},{"id":"27319","type":"CID","arg1_id":"27299","arg2_id":"27305","normalized":[]},{"id":"27320","type":"CID","arg1_id":"27299","arg2_id":"27313","normalized":[]},{"id":"27321","type":"CID","arg1_id":"27300","arg2_id":"27297","normalized":[]},{"id":"27322","type":"CID","arg1_id":"27300","arg2_id":"27305","normalized":[]},{"id":"27323","type":"CID","arg1_id":"27300","arg2_id":"27313","normalized":[]},{"id":"27324","type":"CID","arg1_id":"27302","arg2_id":"27297","normalized":[]},{"id":"27325","type":"CID","arg1_id":"27302","arg2_id":"27305","normalized":[]},{"id":"27326","type":"CID","arg1_id":"27302","arg2_id":"27313","normalized":[]},{"id":"27327","type":"CID","arg1_id":"27306","arg2_id":"27297","normalized":[]},{"id":"27328","type":"CID","arg1_id":"27306","arg2_id":"27305","normalized":[]},{"id":"27329","type":"CID","arg1_id":"27306","arg2_id":"27313","normalized":[]},{"id":"27330","type":"CID","arg1_id":"27307","arg2_id":"27297","normalized":[]},{"id":"27331","type":"CID","arg1_id":"27307","arg2_id":"27305","normalized":[]},{"id":"27332","type":"CID","arg1_id":"27307","arg2_id":"27313","normalized":[]},{"id":"27333","type":"CID","arg1_id":"27309","arg2_id":"27297","normalized":[]},{"id":"27334","type":"CID","arg1_id":"27309","arg2_id":"27305","normalized":[]},{"id":"27335","type":"CID","arg1_id":"27309","arg2_id":"27313","normalized":[]},{"id":"27336","type":"CID","arg1_id":"27312","arg2_id":"27297","normalized":[]},{"id":"27337","type":"CID","arg1_id":"27312","arg2_id":"27305","normalized":[]},{"id":"27338","type":"CID","arg1_id":"27312","arg2_id":"27313","normalized":[]}]}
{"id":"27339","document_id":"8494478","passages":[{"id":"27340","type":"title","text":["Ciprofloxacin-induced nephrotoxicity in patients with cancer."],"offsets":[[0,61]]},{"id":"27341","type":"abstract","text":["Nephrotoxicity associated with ciprofloxacin is uncommon. Five patients with cancer who developed acute renal failure that followed treatment with ciprofloxacin are described and an additional 15 cases reported in the literature are reviewed. Other than elevation of serum creatinine levels, characteristic clinical manifestations and abnormal laboratory findings are not frequently present. Allergic interstitial nephritis is believed to be the underlying pathological-process. Definitive diagnosis requires performance of renal biopsy, although this is not always feasible. An improvement in renal function that followed the discontinuation of the offending antibiotic supports the presumptive diagnosis of ciprofloxacin-induced acute renal failure."],"offsets":[[62,813]]}],"entities":[{"id":"27342","type":"Chemical","text":["Ciprofloxacin"],"offsets":[[0,13]],"normalized":[{"db_name":"MESH","db_id":"D002939"}]},{"id":"27343","type":"Disease","text":["nephrotoxicity"],"offsets":[[22,36]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"27344","type":"Disease","text":["cancer"],"offsets":[[54,60]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"27345","type":"Disease","text":["Nephrotoxicity"],"offsets":[[62,76]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"27346","type":"Chemical","text":["ciprofloxacin"],"offsets":[[93,106]],"normalized":[{"db_name":"MESH","db_id":"D002939"}]},{"id":"27347","type":"Disease","text":["cancer"],"offsets":[[139,145]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"27348","type":"Disease","text":["acute renal failure"],"offsets":[[160,179]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"27349","type":"Chemical","text":["ciprofloxacin"],"offsets":[[209,222]],"normalized":[{"db_name":"MESH","db_id":"D002939"}]},{"id":"27350","type":"Chemical","text":["creatinine"],"offsets":[[335,345]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"27351","type":"Disease","text":["interstitial nephritis"],"offsets":[[463,485]],"normalized":[{"db_name":"MESH","db_id":"D009395"}]},{"id":"27352","type":"Chemical","text":["ciprofloxacin"],"offsets":[[771,784]],"normalized":[{"db_name":"MESH","db_id":"D002939"}]},{"id":"27353","type":"Disease","text":["acute renal failure"],"offsets":[[793,812]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]}],"events":[],"coreferences":[],"relations":[{"id":"27354","type":"CID","arg1_id":"27342","arg2_id":"27348","normalized":[]},{"id":"27355","type":"CID","arg1_id":"27342","arg2_id":"27353","normalized":[]},{"id":"27356","type":"CID","arg1_id":"27346","arg2_id":"27348","normalized":[]},{"id":"27357","type":"CID","arg1_id":"27346","arg2_id":"27353","normalized":[]},{"id":"27358","type":"CID","arg1_id":"27349","arg2_id":"27348","normalized":[]},{"id":"27359","type":"CID","arg1_id":"27349","arg2_id":"27353","normalized":[]},{"id":"27360","type":"CID","arg1_id":"27352","arg2_id":"27348","normalized":[]},{"id":"27361","type":"CID","arg1_id":"27352","arg2_id":"27353","normalized":[]}]}
{"id":"27362","document_id":"8475949","passages":[{"id":"27363","type":"title","text":["Case report: pentamidine and polymorphic ventricular tachycardia revisited."],"offsets":[[0,75]]},{"id":"27364","type":"abstract","text":["Pentamidine isethionate has been associated with ventricular tachyarrhythmias, including torsade de pointes. This article reports two cases of this complication and reviews all reported cases to date. Pentamidine-induced torsade de pointes may be related to serum magnesium levels and hypomagnesemia may synergistically induce torsade. Torsade de pointes occurred after an average of 10 days of treatment with pentamidine. In these patients, no other acute side effects of pentamidine were observed. Torsade de pointes can be treated when recognized early, possibly without discontinuation of pentamidine. When QTc interval prolongation is observed, early magnesium supplementation is advocated."],"offsets":[[76,771]]}],"entities":[{"id":"27365","type":"Chemical","text":["pentamidine"],"offsets":[[13,24]],"normalized":[{"db_name":"MESH","db_id":"D010419"}]},{"id":"27366","type":"Disease","text":["ventricular tachycardia"],"offsets":[[41,64]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"27367","type":"Chemical","text":["Pentamidine isethionate"],"offsets":[[76,99]],"normalized":[{"db_name":"MESH","db_id":"D010419"}]},{"id":"27368","type":"Disease","text":["ventricular tachyarrhythmias"],"offsets":[[125,153]],"normalized":[{"db_name":"MESH","db_id":"D017180"}]},{"id":"27369","type":"Disease","text":["torsade de pointes"],"offsets":[[165,183]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"27370","type":"Chemical","text":["Pentamidine"],"offsets":[[277,288]],"normalized":[{"db_name":"MESH","db_id":"D010419"}]},{"id":"27371","type":"Disease","text":["torsade de pointes"],"offsets":[[297,315]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"27372","type":"Chemical","text":["magnesium"],"offsets":[[340,349]],"normalized":[{"db_name":"MESH","db_id":"D008274"}]},{"id":"27373","type":"Disease","text":["hypomagnesemia"],"offsets":[[361,375]],"normalized":[{"db_name":"MESH","db_id":"C537153"}]},{"id":"27374","type":"Disease","text":["Torsade de pointes"],"offsets":[[412,430]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"27375","type":"Chemical","text":["pentamidine"],"offsets":[[486,497]],"normalized":[{"db_name":"MESH","db_id":"D010419"}]},{"id":"27376","type":"Chemical","text":["pentamidine"],"offsets":[[549,560]],"normalized":[{"db_name":"MESH","db_id":"D010419"}]},{"id":"27377","type":"Disease","text":["Torsade de pointes"],"offsets":[[576,594]],"normalized":[{"db_name":"MESH","db_id":"D016171"}]},{"id":"27378","type":"Chemical","text":["pentamidine"],"offsets":[[669,680]],"normalized":[{"db_name":"MESH","db_id":"D010419"}]},{"id":"27379","type":"Disease","text":["QTc interval prolongation"],"offsets":[[687,712]],"normalized":[{"db_name":"MESH","db_id":"D008133"}]},{"id":"27380","type":"Chemical","text":["magnesium"],"offsets":[[732,741]],"normalized":[{"db_name":"MESH","db_id":"D008274"}]}],"events":[],"coreferences":[],"relations":[{"id":"27381","type":"CID","arg1_id":"27365","arg2_id":"27369","normalized":[]},{"id":"27382","type":"CID","arg1_id":"27365","arg2_id":"27371","normalized":[]},{"id":"27383","type":"CID","arg1_id":"27365","arg2_id":"27374","normalized":[]},{"id":"27384","type":"CID","arg1_id":"27365","arg2_id":"27377","normalized":[]},{"id":"27385","type":"CID","arg1_id":"27367","arg2_id":"27369","normalized":[]},{"id":"27386","type":"CID","arg1_id":"27367","arg2_id":"27371","normalized":[]},{"id":"27387","type":"CID","arg1_id":"27367","arg2_id":"27374","normalized":[]},{"id":"27388","type":"CID","arg1_id":"27367","arg2_id":"27377","normalized":[]},{"id":"27389","type":"CID","arg1_id":"27370","arg2_id":"27369","normalized":[]},{"id":"27390","type":"CID","arg1_id":"27370","arg2_id":"27371","normalized":[]},{"id":"27391","type":"CID","arg1_id":"27370","arg2_id":"27374","normalized":[]},{"id":"27392","type":"CID","arg1_id":"27370","arg2_id":"27377","normalized":[]},{"id":"27393","type":"CID","arg1_id":"27375","arg2_id":"27369","normalized":[]},{"id":"27394","type":"CID","arg1_id":"27375","arg2_id":"27371","normalized":[]},{"id":"27395","type":"CID","arg1_id":"27375","arg2_id":"27374","normalized":[]},{"id":"27396","type":"CID","arg1_id":"27375","arg2_id":"27377","normalized":[]},{"id":"27397","type":"CID","arg1_id":"27376","arg2_id":"27369","normalized":[]},{"id":"27398","type":"CID","arg1_id":"27376","arg2_id":"27371","normalized":[]},{"id":"27399","type":"CID","arg1_id":"27376","arg2_id":"27374","normalized":[]},{"id":"27400","type":"CID","arg1_id":"27376","arg2_id":"27377","normalized":[]},{"id":"27401","type":"CID","arg1_id":"27378","arg2_id":"27369","normalized":[]},{"id":"27402","type":"CID","arg1_id":"27378","arg2_id":"27371","normalized":[]},{"id":"27403","type":"CID","arg1_id":"27378","arg2_id":"27374","normalized":[]},{"id":"27404","type":"CID","arg1_id":"27378","arg2_id":"27377","normalized":[]}]}
{"id":"27405","document_id":"7710775","passages":[{"id":"27406","type":"title","text":["Time dependence of plasma malondialdehyde, oxypurines, and nucleosides during incomplete cerebral ischemia in the rat."],"offsets":[[0,118]]},{"id":"27407","type":"abstract","text":["Incomplete cerebral ischemia (30 min) was induced in the rat by bilaterally clamping the common carotid arteries. Peripheral venous blood samples were withdrawn from the femoral vein four times (once every 5 min) before ischemia (0 time) and 5, 15, and 30 min after ischemia. Plasma extracts were analyzed by a highly sensitive high-performance liquid chromatographic method for the direct determination of malondialdehyde, oxypurines, and nucleosides. During ischemia, a time-dependent increase of plasma oxypurines and nucleosides was observed. Plasma malondialdehyde, which was present in minimal amount at zero time (0.058 mumol\/liter plasma; SD 0.015), increased after 5 min of ischemia, resulting in a fivefold increase after 30 min of carotid occlusion (0.298 mumol\/liter plasma; SD 0.078). Increased plasma malondialdehyde was also recorded in two other groups of animals subjected to the same experimental model, one receiving 20 mg\/kg b.w. of the cyclooxygenase inhibitor acetylsalicylate intravenously immediately before ischemia, the other receiving 650 micrograms\/kg b.w. of the hypotensive drug nitroprusside at a flow rate of 103 microliters\/min intravenously during ischemia, although in this latter group malondialdehyde was significantly higher. The present data indicate that the determination of malondialdehyde, oxypurines, and nucleosides in peripheral blood, may be used to monitor the metabolic alterations of tissues occurring during ischemic phenomena.(ABSTRACT TRUNCATED AT 250 WORDS)"],"offsets":[[119,1630]]}],"entities":[{"id":"27408","type":"Chemical","text":["malondialdehyde"],"offsets":[[26,41]],"normalized":[{"db_name":"MESH","db_id":"D008315"}]},{"id":"27409","type":"Chemical","text":["oxypurines"],"offsets":[[43,53]],"normalized":[]},{"id":"27410","type":"Chemical","text":["nucleosides"],"offsets":[[59,70]],"normalized":[{"db_name":"MESH","db_id":"D009705"}]},{"id":"27411","type":"Disease","text":["cerebral ischemia"],"offsets":[[89,106]],"normalized":[{"db_name":"MESH","db_id":"D002545"}]},{"id":"27412","type":"Disease","text":["cerebral ischemia"],"offsets":[[130,147]],"normalized":[{"db_name":"MESH","db_id":"D002545"}]},{"id":"27413","type":"Disease","text":["ischemia"],"offsets":[[339,347]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"27414","type":"Disease","text":["ischemia"],"offsets":[[385,393]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"27415","type":"Chemical","text":["malondialdehyde"],"offsets":[[526,541]],"normalized":[{"db_name":"MESH","db_id":"D008315"}]},{"id":"27416","type":"Chemical","text":["oxypurines"],"offsets":[[543,553]],"normalized":[]},{"id":"27417","type":"Chemical","text":["nucleosides"],"offsets":[[559,570]],"normalized":[{"db_name":"MESH","db_id":"D009705"}]},{"id":"27418","type":"Disease","text":["ischemia"],"offsets":[[579,587]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"27419","type":"Chemical","text":["oxypurines"],"offsets":[[625,635]],"normalized":[]},{"id":"27420","type":"Chemical","text":["nucleosides"],"offsets":[[640,651]],"normalized":[{"db_name":"MESH","db_id":"D009705"}]},{"id":"27421","type":"Chemical","text":["malondialdehyde"],"offsets":[[673,688]],"normalized":[{"db_name":"MESH","db_id":"D008315"}]},{"id":"27422","type":"Disease","text":["ischemia"],"offsets":[[802,810]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"27423","type":"Chemical","text":["malondialdehyde"],"offsets":[[934,949]],"normalized":[{"db_name":"MESH","db_id":"D008315"}]},{"id":"27424","type":"Chemical","text":["acetylsalicylate"],"offsets":[[1101,1117]],"normalized":[{"db_name":"MESH","db_id":"D001241"}]},{"id":"27425","type":"Disease","text":["ischemia"],"offsets":[[1151,1159]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"27426","type":"Disease","text":["hypotensive"],"offsets":[[1211,1222]],"normalized":[{"db_name":"MESH","db_id":"D007022"}]},{"id":"27427","type":"Chemical","text":["nitroprusside"],"offsets":[[1228,1241]],"normalized":[{"db_name":"MESH","db_id":"D009599"}]},{"id":"27428","type":"Disease","text":["ischemia"],"offsets":[[1301,1309]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]},{"id":"27429","type":"Chemical","text":["malondialdehyde"],"offsets":[[1341,1356]],"normalized":[{"db_name":"MESH","db_id":"D008315"}]},{"id":"27430","type":"Chemical","text":["malondialdehyde"],"offsets":[[1435,1450]],"normalized":[{"db_name":"MESH","db_id":"D008315"}]},{"id":"27431","type":"Chemical","text":["oxypurines"],"offsets":[[1452,1462]],"normalized":[]},{"id":"27432","type":"Chemical","text":["nucleosides"],"offsets":[[1468,1479]],"normalized":[{"db_name":"MESH","db_id":"D009705"}]},{"id":"27433","type":"Disease","text":["ischemic"],"offsets":[[1578,1586]],"normalized":[{"db_name":"MESH","db_id":"D007511"}]}],"events":[],"coreferences":[],"relations":[{"id":"27434","type":"CID","arg1_id":"27408","arg2_id":"27411","normalized":[]},{"id":"27435","type":"CID","arg1_id":"27408","arg2_id":"27412","normalized":[]},{"id":"27436","type":"CID","arg1_id":"27415","arg2_id":"27411","normalized":[]},{"id":"27437","type":"CID","arg1_id":"27415","arg2_id":"27412","normalized":[]},{"id":"27438","type":"CID","arg1_id":"27421","arg2_id":"27411","normalized":[]},{"id":"27439","type":"CID","arg1_id":"27421","arg2_id":"27412","normalized":[]},{"id":"27440","type":"CID","arg1_id":"27423","arg2_id":"27411","normalized":[]},{"id":"27441","type":"CID","arg1_id":"27423","arg2_id":"27412","normalized":[]},{"id":"27442","type":"CID","arg1_id":"27429","arg2_id":"27411","normalized":[]},{"id":"27443","type":"CID","arg1_id":"27429","arg2_id":"27412","normalized":[]},{"id":"27444","type":"CID","arg1_id":"27430","arg2_id":"27411","normalized":[]},{"id":"27445","type":"CID","arg1_id":"27430","arg2_id":"27412","normalized":[]}]}
{"id":"27446","document_id":"7650771","passages":[{"id":"27447","type":"title","text":["Cholinergic toxicity resulting from ocular instillation of echothiophate iodide eye drops."],"offsets":[[0,90]]},{"id":"27448","type":"abstract","text":["A patient developed a severe cholinergic syndrome from the use of echothiophate iodide ophthalmic drops, presented with profound muscle weakness and was initially given the diagnosis of myasthenia gravis. Red blood cell and serum cholinesterase levels were severely depressed and symptoms resolved spontaneously following discontinuation of the eye drops."],"offsets":[[91,446]]}],"entities":[{"id":"27449","type":"Disease","text":["toxicity"],"offsets":[[12,20]],"normalized":[{"db_name":"MESH","db_id":"D064420"}]},{"id":"27450","type":"Chemical","text":["echothiophate iodide"],"offsets":[[59,79]],"normalized":[{"db_name":"MESH","db_id":"D004456"}]},{"id":"27451","type":"Chemical","text":["echothiophate iodide"],"offsets":[[157,177]],"normalized":[{"db_name":"MESH","db_id":"D004456"}]},{"id":"27452","type":"Disease","text":["muscle weakness"],"offsets":[[220,235]],"normalized":[{"db_name":"MESH","db_id":"D018908"}]},{"id":"27453","type":"Disease","text":["myasthenia gravis"],"offsets":[[277,294]],"normalized":[{"db_name":"MESH","db_id":"D009157"}]}],"events":[],"coreferences":[],"relations":[{"id":"27454","type":"CID","arg1_id":"27450","arg2_id":"27452","normalized":[]},{"id":"27455","type":"CID","arg1_id":"27451","arg2_id":"27452","normalized":[]}]}
{"id":"27456","document_id":"7565311","passages":[{"id":"27457","type":"title","text":["Acute renal failure in high dose carboplatin chemotherapy."],"offsets":[[0,58]]},{"id":"27458","type":"abstract","text":["Carboplatin has been reported to cause acute renal failure when administered in high doses to adult patients. We report a 4 1\/2-year-old girl who was treated with high-dose carboplatin for metastatic parameningeal embryonal rhabdomyosarcoma. Acute renal failure developed followed by a slow partial recovery of renal function. Possible contributing factors are discussed."],"offsets":[[59,430]]}],"entities":[{"id":"27459","type":"Disease","text":["Acute renal failure"],"offsets":[[0,19]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"27460","type":"Chemical","text":["carboplatin"],"offsets":[[33,44]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"27461","type":"Chemical","text":["Carboplatin"],"offsets":[[59,70]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"27462","type":"Disease","text":["acute renal failure"],"offsets":[[98,117]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]},{"id":"27463","type":"Chemical","text":["carboplatin"],"offsets":[[232,243]],"normalized":[{"db_name":"MESH","db_id":"D016190"}]},{"id":"27464","type":"Disease","text":["embryonal rhabdomyosarcoma"],"offsets":[[273,299]],"normalized":[{"db_name":"MESH","db_id":"D018233"}]},{"id":"27465","type":"Disease","text":["Acute renal failure"],"offsets":[[301,320]],"normalized":[{"db_name":"MESH","db_id":"D058186"}]}],"events":[],"coreferences":[],"relations":[{"id":"27466","type":"CID","arg1_id":"27460","arg2_id":"27459","normalized":[]},{"id":"27467","type":"CID","arg1_id":"27460","arg2_id":"27462","normalized":[]},{"id":"27468","type":"CID","arg1_id":"27460","arg2_id":"27465","normalized":[]},{"id":"27469","type":"CID","arg1_id":"27461","arg2_id":"27459","normalized":[]},{"id":"27470","type":"CID","arg1_id":"27461","arg2_id":"27462","normalized":[]},{"id":"27471","type":"CID","arg1_id":"27461","arg2_id":"27465","normalized":[]},{"id":"27472","type":"CID","arg1_id":"27463","arg2_id":"27459","normalized":[]},{"id":"27473","type":"CID","arg1_id":"27463","arg2_id":"27462","normalized":[]},{"id":"27474","type":"CID","arg1_id":"27463","arg2_id":"27465","normalized":[]}]}
{"id":"27475","document_id":"7421734","passages":[{"id":"27476","type":"title","text":["Endometrial carcinoma after Hodgkin disease in childhood."],"offsets":[[0,57]]},{"id":"27477","type":"abstract","text":["A 34-year-old patient developed metastic endometrial carcinoma after Hodgkin disease in childhood. She had ovarian failure after abdominal irradiation and chemotherapy for Hodgkin disease, and received exogenous estrogens, a treatment implicated in the development of endometrial cancer in menopausal women. Young women on replacement estrogens for ovarian failure after cancer therapy may also have increased risk of endometrial carcinoma and should be examined periodically."],"offsets":[[58,534]]}],"entities":[{"id":"27478","type":"Disease","text":["Endometrial carcinoma"],"offsets":[[0,21]],"normalized":[{"db_name":"MESH","db_id":"D016889"}]},{"id":"27479","type":"Disease","text":["Hodgkin disease"],"offsets":[[28,43]],"normalized":[{"db_name":"MESH","db_id":"D006689"}]},{"id":"27480","type":"Disease","text":["endometrial carcinoma"],"offsets":[[99,120]],"normalized":[{"db_name":"MESH","db_id":"D016889"}]},{"id":"27481","type":"Disease","text":["Hodgkin disease"],"offsets":[[127,142]],"normalized":[{"db_name":"MESH","db_id":"D006689"}]},{"id":"27482","type":"Disease","text":["ovarian failure"],"offsets":[[165,180]],"normalized":[{"db_name":"MESH","db_id":"D010049"}]},{"id":"27483","type":"Disease","text":["Hodgkin disease"],"offsets":[[230,245]],"normalized":[{"db_name":"MESH","db_id":"D006689"}]},{"id":"27484","type":"Chemical","text":["estrogens"],"offsets":[[270,279]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"27485","type":"Disease","text":["endometrial cancer"],"offsets":[[326,344]],"normalized":[{"db_name":"MESH","db_id":"D016889"}]},{"id":"27486","type":"Chemical","text":["estrogens"],"offsets":[[393,402]],"normalized":[{"db_name":"MESH","db_id":"D004967"}]},{"id":"27487","type":"Disease","text":["ovarian failure"],"offsets":[[407,422]],"normalized":[{"db_name":"MESH","db_id":"D010049"}]},{"id":"27488","type":"Disease","text":["cancer"],"offsets":[[429,435]],"normalized":[{"db_name":"MESH","db_id":"D009369"}]},{"id":"27489","type":"Disease","text":["endometrial carcinoma"],"offsets":[[476,497]],"normalized":[{"db_name":"MESH","db_id":"D016889"}]}],"events":[],"coreferences":[],"relations":[{"id":"27490","type":"CID","arg1_id":"27484","arg2_id":"27478","normalized":[]},{"id":"27491","type":"CID","arg1_id":"27484","arg2_id":"27480","normalized":[]},{"id":"27492","type":"CID","arg1_id":"27484","arg2_id":"27485","normalized":[]},{"id":"27493","type":"CID","arg1_id":"27484","arg2_id":"27489","normalized":[]},{"id":"27494","type":"CID","arg1_id":"27486","arg2_id":"27478","normalized":[]},{"id":"27495","type":"CID","arg1_id":"27486","arg2_id":"27480","normalized":[]},{"id":"27496","type":"CID","arg1_id":"27486","arg2_id":"27485","normalized":[]},{"id":"27497","type":"CID","arg1_id":"27486","arg2_id":"27489","normalized":[]}]}
{"id":"27498","document_id":"6732043","passages":[{"id":"27499","type":"title","text":["Induction of the obstructive sleep apnea syndrome in a woman by exogenous androgen administration."],"offsets":[[0,98]]},{"id":"27500","type":"abstract","text":["We documented airway occlusion during sleep and an abnormally high supraglottic resistance while awake in a 54-yr-old woman who had developed physical changes and the syndrome of obstructive sleep apnea while being administered exogenous androgens. When the androgens were withdrawn, the patient's physical changes, symptoms, sleep study, and supraglottic resistance all returned to normal. A rechallenge with androgen produced symptoms of obstructive sleep apnea that abated upon withdrawal of the hormone. Previous reports have favored a role of androgens in the pathogenesis of sleep apnea. Our report provides direct evidence for this role. Structural and functional measurements indicate that androgens exert a permissive or necessary action on the structural configuration of the oropharynx that predisposes to obstruction during sleep. Development of the obstructive sleep apnea syndrome must be considered a possible side effect of androgen therapy."],"offsets":[[99,1056]]}],"entities":[{"id":"27501","type":"Disease","text":["obstructive sleep apnea syndrome"],"offsets":[[17,49]],"normalized":[{"db_name":"MESH","db_id":"D020181"}]},{"id":"27502","type":"Chemical","text":["androgen"],"offsets":[[74,82]],"normalized":[{"db_name":"MESH","db_id":"D000728"}]},{"id":"27503","type":"Disease","text":["syndrome of obstructive sleep apnea"],"offsets":[[266,301]],"normalized":[{"db_name":"MESH","db_id":"D020181"}]},{"id":"27504","type":"Chemical","text":["androgens"],"offsets":[[337,346]],"normalized":[{"db_name":"MESH","db_id":"D000728"}]},{"id":"27505","type":"Chemical","text":["androgens"],"offsets":[[357,366]],"normalized":[{"db_name":"MESH","db_id":"D000728"}]},{"id":"27506","type":"Chemical","text":["androgen"],"offsets":[[509,517]],"normalized":[{"db_name":"MESH","db_id":"D000728"}]},{"id":"27507","type":"Disease","text":["obstructive sleep apnea"],"offsets":[[539,562]],"normalized":[{"db_name":"MESH","db_id":"D020181"}]},{"id":"27508","type":"Chemical","text":["androgens"],"offsets":[[647,656]],"normalized":[{"db_name":"MESH","db_id":"D000728"}]},{"id":"27509","type":"Disease","text":["sleep apnea"],"offsets":[[680,691]],"normalized":[{"db_name":"MESH","db_id":"D012891"}]},{"id":"27510","type":"Chemical","text":["androgens"],"offsets":[[797,806]],"normalized":[{"db_name":"MESH","db_id":"D000728"}]},{"id":"27511","type":"Disease","text":["obstructive sleep apnea syndrome"],"offsets":[[961,993]],"normalized":[{"db_name":"MESH","db_id":"D020181"}]},{"id":"27512","type":"Chemical","text":["androgen"],"offsets":[[1039,1047]],"normalized":[{"db_name":"MESH","db_id":"D000728"}]}],"events":[],"coreferences":[],"relations":[{"id":"27513","type":"CID","arg1_id":"27502","arg2_id":"27501","normalized":[]},{"id":"27514","type":"CID","arg1_id":"27502","arg2_id":"27503","normalized":[]},{"id":"27515","type":"CID","arg1_id":"27502","arg2_id":"27507","normalized":[]},{"id":"27516","type":"CID","arg1_id":"27502","arg2_id":"27511","normalized":[]},{"id":"27517","type":"CID","arg1_id":"27504","arg2_id":"27501","normalized":[]},{"id":"27518","type":"CID","arg1_id":"27504","arg2_id":"27503","normalized":[]},{"id":"27519","type":"CID","arg1_id":"27504","arg2_id":"27507","normalized":[]},{"id":"27520","type":"CID","arg1_id":"27504","arg2_id":"27511","normalized":[]},{"id":"27521","type":"CID","arg1_id":"27505","arg2_id":"27501","normalized":[]},{"id":"27522","type":"CID","arg1_id":"27505","arg2_id":"27503","normalized":[]},{"id":"27523","type":"CID","arg1_id":"27505","arg2_id":"27507","normalized":[]},{"id":"27524","type":"CID","arg1_id":"27505","arg2_id":"27511","normalized":[]},{"id":"27525","type":"CID","arg1_id":"27506","arg2_id":"27501","normalized":[]},{"id":"27526","type":"CID","arg1_id":"27506","arg2_id":"27503","normalized":[]},{"id":"27527","type":"CID","arg1_id":"27506","arg2_id":"27507","normalized":[]},{"id":"27528","type":"CID","arg1_id":"27506","arg2_id":"27511","normalized":[]},{"id":"27529","type":"CID","arg1_id":"27508","arg2_id":"27501","normalized":[]},{"id":"27530","type":"CID","arg1_id":"27508","arg2_id":"27503","normalized":[]},{"id":"27531","type":"CID","arg1_id":"27508","arg2_id":"27507","normalized":[]},{"id":"27532","type":"CID","arg1_id":"27508","arg2_id":"27511","normalized":[]},{"id":"27533","type":"CID","arg1_id":"27510","arg2_id":"27501","normalized":[]},{"id":"27534","type":"CID","arg1_id":"27510","arg2_id":"27503","normalized":[]},{"id":"27535","type":"CID","arg1_id":"27510","arg2_id":"27507","normalized":[]},{"id":"27536","type":"CID","arg1_id":"27510","arg2_id":"27511","normalized":[]},{"id":"27537","type":"CID","arg1_id":"27512","arg2_id":"27501","normalized":[]},{"id":"27538","type":"CID","arg1_id":"27512","arg2_id":"27503","normalized":[]},{"id":"27539","type":"CID","arg1_id":"27512","arg2_id":"27507","normalized":[]},{"id":"27540","type":"CID","arg1_id":"27512","arg2_id":"27511","normalized":[]}]}
{"id":"27541","document_id":"6454943","passages":[{"id":"27542","type":"title","text":["Effect of captopril on pre-existing and aminonucleoside-induced proteinuria in spontaneously hypertensive rats."],"offsets":[[0,111]]},{"id":"27543","type":"abstract","text":["Proteinuria is a side effect of captopril treatment in hypertensive patients. The possibility of reproducing the same renal abnormality with captopril was examined in SHR. Oral administration of captopril at 100 mg\/kg for 14 days failed to aggravate proteinuria pre-existing in SHR. Also, captopril treatment failed to potentiate or facilitate development of massive proteinuria invoked by puromycin aminonucleoside in SHR. Captopril had little or no demonstrable effects on serum electrolyte concentrations, excretion of urine, sodium and potassium, endogenous creatinine clearance, body weight, and food and water consumption. However, ketone bodies were consistently present in urine and several lethalities occurred during multiple dosing of captopril in SHR."],"offsets":[[112,875]]}],"entities":[{"id":"27544","type":"Chemical","text":["captopril"],"offsets":[[10,19]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"27545","type":"Chemical","text":["aminonucleoside"],"offsets":[[40,55]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"27546","type":"Disease","text":["proteinuria"],"offsets":[[64,75]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"27547","type":"Disease","text":["hypertensive"],"offsets":[[93,105]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"27548","type":"Disease","text":["Proteinuria"],"offsets":[[112,123]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"27549","type":"Chemical","text":["captopril"],"offsets":[[144,153]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"27550","type":"Disease","text":["hypertensive"],"offsets":[[167,179]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"27551","type":"Disease","text":["renal abnormality"],"offsets":[[230,247]],"normalized":[{"db_name":"MESH","db_id":"D007674"}]},{"id":"27552","type":"Chemical","text":["captopril"],"offsets":[[253,262]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"27553","type":"Chemical","text":["captopril"],"offsets":[[307,316]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"27554","type":"Disease","text":["proteinuria"],"offsets":[[362,373]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"27555","type":"Chemical","text":["captopril"],"offsets":[[401,410]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"27556","type":"Disease","text":["proteinuria"],"offsets":[[479,490]],"normalized":[{"db_name":"MESH","db_id":"D011507"}]},{"id":"27557","type":"Chemical","text":["puromycin aminonucleoside"],"offsets":[[502,527]],"normalized":[{"db_name":"MESH","db_id":"D011692"}]},{"id":"27558","type":"Chemical","text":["Captopril"],"offsets":[[536,545]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]},{"id":"27559","type":"Chemical","text":["sodium"],"offsets":[[641,647]],"normalized":[{"db_name":"MESH","db_id":"D012964"}]},{"id":"27560","type":"Chemical","text":["potassium"],"offsets":[[652,661]],"normalized":[{"db_name":"MESH","db_id":"D011188"}]},{"id":"27561","type":"Chemical","text":["creatinine"],"offsets":[[674,684]],"normalized":[{"db_name":"MESH","db_id":"D003404"}]},{"id":"27562","type":"Chemical","text":["ketone"],"offsets":[[750,756]],"normalized":[{"db_name":"MESH","db_id":"D007659"}]},{"id":"27563","type":"Chemical","text":["captopril"],"offsets":[[858,867]],"normalized":[{"db_name":"MESH","db_id":"D002216"}]}],"events":[],"coreferences":[],"relations":[{"id":"27564","type":"CID","arg1_id":"27545","arg2_id":"27546","normalized":[]},{"id":"27565","type":"CID","arg1_id":"27545","arg2_id":"27548","normalized":[]},{"id":"27566","type":"CID","arg1_id":"27545","arg2_id":"27554","normalized":[]},{"id":"27567","type":"CID","arg1_id":"27545","arg2_id":"27556","normalized":[]},{"id":"27568","type":"CID","arg1_id":"27557","arg2_id":"27546","normalized":[]},{"id":"27569","type":"CID","arg1_id":"27557","arg2_id":"27548","normalized":[]},{"id":"27570","type":"CID","arg1_id":"27557","arg2_id":"27554","normalized":[]},{"id":"27571","type":"CID","arg1_id":"27557","arg2_id":"27556","normalized":[]}]}
{"id":"27572","document_id":"6153967","passages":[{"id":"27573","type":"title","text":["Epileptogenic properties of enflurane and their clinical interpretation."],"offsets":[[0,72]]},{"id":"27574","type":"abstract","text":["Three cases of EEG changes induced by single exposure to enflurane anesthesia are reported. In one patient, enflurane administered during a donor nephrectomy resulted in unexpected partial motor seizures. Until the cause of the seizures was correctly identified, the patient was inappropriately treated with anticonvulsants. Two other patients suffered from partial, complex and generalized seizures uncontrolled by medication. Epileptic foci delineated and activated by enflurane were surgically ablated and the patients are now seizure-free. Previous exposures to enflurane have to be disclosed to avoid mistakes in clinical interpretation of the EEG. On the other hand, enflurane may prove to be a safe fast acting activator of epileptic foci during corticography or depth electrode intraoperative recordings."],"offsets":[[73,885]]}],"entities":[{"id":"27575","type":"Chemical","text":["enflurane"],"offsets":[[28,37]],"normalized":[{"db_name":"MESH","db_id":"D004737"}]},{"id":"27576","type":"Chemical","text":["enflurane"],"offsets":[[130,139]],"normalized":[{"db_name":"MESH","db_id":"D004737"}]},{"id":"27577","type":"Chemical","text":["enflurane"],"offsets":[[181,190]],"normalized":[{"db_name":"MESH","db_id":"D004737"}]},{"id":"27578","type":"Disease","text":["seizures"],"offsets":[[268,276]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"27579","type":"Disease","text":["seizures"],"offsets":[[301,309]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"27580","type":"Disease","text":["seizures"],"offsets":[[464,472]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"27581","type":"Disease","text":["Epileptic"],"offsets":[[501,510]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]},{"id":"27582","type":"Chemical","text":["enflurane"],"offsets":[[544,553]],"normalized":[{"db_name":"MESH","db_id":"D004737"}]},{"id":"27583","type":"Disease","text":["seizure"],"offsets":[[603,610]],"normalized":[{"db_name":"MESH","db_id":"D012640"}]},{"id":"27584","type":"Chemical","text":["enflurane"],"offsets":[[639,648]],"normalized":[{"db_name":"MESH","db_id":"D004737"}]},{"id":"27585","type":"Chemical","text":["enflurane"],"offsets":[[746,755]],"normalized":[{"db_name":"MESH","db_id":"D004737"}]},{"id":"27586","type":"Disease","text":["epileptic"],"offsets":[[804,813]],"normalized":[{"db_name":"MESH","db_id":"D004827"}]}],"events":[],"coreferences":[],"relations":[{"id":"27587","type":"CID","arg1_id":"27575","arg2_id":"27578","normalized":[]},{"id":"27588","type":"CID","arg1_id":"27575","arg2_id":"27579","normalized":[]},{"id":"27589","type":"CID","arg1_id":"27575","arg2_id":"27580","normalized":[]},{"id":"27590","type":"CID","arg1_id":"27575","arg2_id":"27583","normalized":[]},{"id":"27591","type":"CID","arg1_id":"27576","arg2_id":"27578","normalized":[]},{"id":"27592","type":"CID","arg1_id":"27576","arg2_id":"27579","normalized":[]},{"id":"27593","type":"CID","arg1_id":"27576","arg2_id":"27580","normalized":[]},{"id":"27594","type":"CID","arg1_id":"27576","arg2_id":"27583","normalized":[]},{"id":"27595","type":"CID","arg1_id":"27577","arg2_id":"27578","normalized":[]},{"id":"27596","type":"CID","arg1_id":"27577","arg2_id":"27579","normalized":[]},{"id":"27597","type":"CID","arg1_id":"27577","arg2_id":"27580","normalized":[]},{"id":"27598","type":"CID","arg1_id":"27577","arg2_id":"27583","normalized":[]},{"id":"27599","type":"CID","arg1_id":"27582","arg2_id":"27578","normalized":[]},{"id":"27600","type":"CID","arg1_id":"27582","arg2_id":"27579","normalized":[]},{"id":"27601","type":"CID","arg1_id":"27582","arg2_id":"27580","normalized":[]},{"id":"27602","type":"CID","arg1_id":"27582","arg2_id":"27583","normalized":[]},{"id":"27603","type":"CID","arg1_id":"27584","arg2_id":"27578","normalized":[]},{"id":"27604","type":"CID","arg1_id":"27584","arg2_id":"27579","normalized":[]},{"id":"27605","type":"CID","arg1_id":"27584","arg2_id":"27580","normalized":[]},{"id":"27606","type":"CID","arg1_id":"27584","arg2_id":"27583","normalized":[]},{"id":"27607","type":"CID","arg1_id":"27585","arg2_id":"27578","normalized":[]},{"id":"27608","type":"CID","arg1_id":"27585","arg2_id":"27579","normalized":[]},{"id":"27609","type":"CID","arg1_id":"27585","arg2_id":"27580","normalized":[]},{"id":"27610","type":"CID","arg1_id":"27585","arg2_id":"27583","normalized":[]}]}
{"id":"27611","document_id":"3183120","passages":[{"id":"27612","type":"title","text":["Reversible cerebral lesions associated with tiazofurin usage: MR demonstration."],"offsets":[[0,79]]},{"id":"27613","type":"abstract","text":["Tiazofurin is an experimental chemotherapeutic agent currently undergoing clinical evaluation. We report our results with magnetic resonance (MR) in demonstrating reversible cerebral abnormalities concurrent with the use of this drug. The abnormalities on MR were correlated with findings on CT as well as with cerebral angiography. The utility of MR in the evaluation of patients receiving this new agent is illustrated."],"offsets":[[80,501]]}],"entities":[{"id":"27614","type":"Disease","text":["cerebral lesions"],"offsets":[[11,27]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]},{"id":"27615","type":"Chemical","text":["tiazofurin"],"offsets":[[44,54]],"normalized":[{"db_name":"MESH","db_id":"C033706"}]},{"id":"27616","type":"Chemical","text":["Tiazofurin"],"offsets":[[80,90]],"normalized":[{"db_name":"MESH","db_id":"C033706"}]},{"id":"27617","type":"Disease","text":["cerebral abnormalities"],"offsets":[[254,276]],"normalized":[{"db_name":"MESH","db_id":"D001927"}]}],"events":[],"coreferences":[],"relations":[{"id":"27618","type":"CID","arg1_id":"27615","arg2_id":"27614","normalized":[]},{"id":"27619","type":"CID","arg1_id":"27615","arg2_id":"27617","normalized":[]},{"id":"27620","type":"CID","arg1_id":"27616","arg2_id":"27614","normalized":[]},{"id":"27621","type":"CID","arg1_id":"27616","arg2_id":"27617","normalized":[]}]}
{"id":"27622","document_id":"3120485","passages":[{"id":"27623","type":"title","text":["Antagonism of diazepam-induced sedative effects by Ro15-1788 in patients after surgery under lumbar epidural block. A double-blind placebo-controlled investigation of efficacy and safety."],"offsets":[[0,187]]},{"id":"27624","type":"abstract","text":["The aim of this study was to assess the efficacy of Ro15-1788 and a placebo in reversing diazepam-induced effects after surgery under epidural block, and to evaluate the local tolerance and general safety of Ro15-1788. Fifty-seven patients were sedated with diazepam for surgery under epidural anaesthesia. Antagonism of diazepam-induced effects by Ro15-1788 was investigated postoperatively in a double-blind placebo-controlled trial. The patient's subjective assessment of mood rating, an objective test of performance, a test for amnesia, and vital signs were recorded for up to 300 min after administration of the trial drug. No significant differences between the two groups were observed for mood rating, amnesia, or vital signs. The Ro15-1788 group showed a significant improvement in the performance test up to 120 min after administration of the drug. There was no evidence of reaction at the injection site."],"offsets":[[188,1105]]}],"entities":[{"id":"27625","type":"Chemical","text":["diazepam"],"offsets":[[14,22]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"27626","type":"Chemical","text":["Ro15-1788"],"offsets":[[51,60]],"normalized":[{"db_name":"MESH","db_id":"D005442"}]},{"id":"27627","type":"Chemical","text":["Ro15-1788"],"offsets":[[240,249]],"normalized":[{"db_name":"MESH","db_id":"D005442"}]},{"id":"27628","type":"Chemical","text":["diazepam"],"offsets":[[277,285]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"27629","type":"Chemical","text":["Ro15-1788"],"offsets":[[396,405]],"normalized":[{"db_name":"MESH","db_id":"D005442"}]},{"id":"27630","type":"Chemical","text":["diazepam"],"offsets":[[446,454]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"27631","type":"Chemical","text":["diazepam"],"offsets":[[509,517]],"normalized":[{"db_name":"MESH","db_id":"D003975"}]},{"id":"27632","type":"Chemical","text":["Ro15-1788"],"offsets":[[537,546]],"normalized":[{"db_name":"MESH","db_id":"D005442"}]},{"id":"27633","type":"Disease","text":["amnesia"],"offsets":[[721,728]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"27634","type":"Disease","text":["amnesia"],"offsets":[[899,906]],"normalized":[{"db_name":"MESH","db_id":"D000647"}]},{"id":"27635","type":"Chemical","text":["Ro15-1788"],"offsets":[[928,937]],"normalized":[{"db_name":"MESH","db_id":"D005442"}]}],"events":[],"coreferences":[],"relations":[{"id":"27636","type":"CID","arg1_id":"27625","arg2_id":"27633","normalized":[]},{"id":"27637","type":"CID","arg1_id":"27625","arg2_id":"27634","normalized":[]},{"id":"27638","type":"CID","arg1_id":"27628","arg2_id":"27633","normalized":[]},{"id":"27639","type":"CID","arg1_id":"27628","arg2_id":"27634","normalized":[]},{"id":"27640","type":"CID","arg1_id":"27630","arg2_id":"27633","normalized":[]},{"id":"27641","type":"CID","arg1_id":"27630","arg2_id":"27634","normalized":[]},{"id":"27642","type":"CID","arg1_id":"27631","arg2_id":"27633","normalized":[]},{"id":"27643","type":"CID","arg1_id":"27631","arg2_id":"27634","normalized":[]}]}
{"id":"27644","document_id":"2886572","passages":[{"id":"27645","type":"title","text":["Enhanced stimulus-induced neurotransmitter overflow in epinephrine-induced hypertensive rats is not mediated by prejunctional beta-adrenoceptor activation."],"offsets":[[0,155]]},{"id":"27646","type":"abstract","text":["The present study examines the effect of 6-day epinephrine treatment (100 micrograms\/kg per h, s.c.) on stimulus-induced (1 Hz) endogenous neurotransmitter overflow from the isolated perfused kidney of vehicle- and epinephrine-treated rats. Renal catecholamine stores and stimulus-induced overflow in the vehicle-treated group consisted of norepinephrine only. However, epinephrine treatment resulted in the incorporation of epinephrine into renal catecholamine stores such that approximately 40% of the catecholamine present was epinephrine while the norepinephrine content was reduced by a similar degree. Total tissue catecholamine content of the kidney on a molar basis was unchanged. Stimulus-induced fractional overflow of neurotransmitter from the epinephrine-treated kidneys was approximately twice normal and consisted of both norepinephrine and epinephrine in proportions similar to those found in the kidney. This difference in fractional overflow between groups was not affected by neuronal and extraneuronal uptake blockade. Propranolol had no effect on stimulus-induced overflow in either group. Phentolamine increased stimulus-induced overflow in both groups although the increment in overflow was greater in the epinephrine-treated group. In conclusion, chronic epinephrine treatment results in enhanced fractional neurotransmitter overflow. However, neither alterations in prejunctional beta-adrenoceptor influences nor alterations in neuronal and extraneuronal uptake mechanisms appear to be responsible for this alteration. Furthermore, data obtained with phentolamine alone do not suggest alpha-adrenoceptor desensitization as the cause of the enhanced neurotransmitter overflow after epinephrine treatment."],"offsets":[[156,1883]]}],"entities":[{"id":"27647","type":"Chemical","text":["epinephrine"],"offsets":[[55,66]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"27648","type":"Disease","text":["hypertensive"],"offsets":[[75,87]],"normalized":[{"db_name":"MESH","db_id":"D006973"}]},{"id":"27649","type":"Chemical","text":["epinephrine"],"offsets":[[203,214]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"27650","type":"Chemical","text":["epinephrine"],"offsets":[[371,382]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"27651","type":"Chemical","text":["catecholamine"],"offsets":[[403,416]],"normalized":[{"db_name":"MESH","db_id":"D002395"}]},{"id":"27652","type":"Chemical","text":["norepinephrine"],"offsets":[[496,510]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"27653","type":"Chemical","text":["epinephrine"],"offsets":[[526,537]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"27654","type":"Chemical","text":["epinephrine"],"offsets":[[581,592]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"27655","type":"Chemical","text":["catecholamine"],"offsets":[[604,617]],"normalized":[{"db_name":"MESH","db_id":"D002395"}]},{"id":"27656","type":"Chemical","text":["catecholamine"],"offsets":[[660,673]],"normalized":[{"db_name":"MESH","db_id":"D002395"}]},{"id":"27657","type":"Chemical","text":["epinephrine"],"offsets":[[686,697]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"27658","type":"Chemical","text":["norepinephrine"],"offsets":[[708,722]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"27659","type":"Chemical","text":["catecholamine"],"offsets":[[777,790]],"normalized":[{"db_name":"MESH","db_id":"D002395"}]},{"id":"27660","type":"Chemical","text":["epinephrine"],"offsets":[[911,922]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"27661","type":"Chemical","text":["norepinephrine"],"offsets":[[992,1006]],"normalized":[{"db_name":"MESH","db_id":"D009638"}]},{"id":"27662","type":"Chemical","text":["epinephrine"],"offsets":[[1011,1022]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"27663","type":"Chemical","text":["Propranolol"],"offsets":[[1194,1205]],"normalized":[{"db_name":"MESH","db_id":"D011433"}]},{"id":"27664","type":"Chemical","text":["Phentolamine"],"offsets":[[1266,1278]],"normalized":[{"db_name":"MESH","db_id":"D010646"}]},{"id":"27665","type":"Chemical","text":["epinephrine"],"offsets":[[1384,1395]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"27666","type":"Chemical","text":["epinephrine"],"offsets":[[1434,1445]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]},{"id":"27667","type":"Chemical","text":["phentolamine"],"offsets":[[1731,1743]],"normalized":[{"db_name":"MESH","db_id":"D010646"}]},{"id":"27668","type":"Chemical","text":["epinephrine"],"offsets":[[1861,1872]],"normalized":[{"db_name":"MESH","db_id":"D004837"}]}],"events":[],"coreferences":[],"relations":[{"id":"27669","type":"CID","arg1_id":"27647","arg2_id":"27648","normalized":[]},{"id":"27670","type":"CID","arg1_id":"27649","arg2_id":"27648","normalized":[]},{"id":"27671","type":"CID","arg1_id":"27650","arg2_id":"27648","normalized":[]},{"id":"27672","type":"CID","arg1_id":"27653","arg2_id":"27648","normalized":[]},{"id":"27673","type":"CID","arg1_id":"27654","arg2_id":"27648","normalized":[]},{"id":"27674","type":"CID","arg1_id":"27657","arg2_id":"27648","normalized":[]},{"id":"27675","type":"CID","arg1_id":"27660","arg2_id":"27648","normalized":[]},{"id":"27676","type":"CID","arg1_id":"27662","arg2_id":"27648","normalized":[]},{"id":"27677","type":"CID","arg1_id":"27665","arg2_id":"27648","normalized":[]},{"id":"27678","type":"CID","arg1_id":"27666","arg2_id":"27648","normalized":[]},{"id":"27679","type":"CID","arg1_id":"27668","arg2_id":"27648","normalized":[]}]}
{"id":"27680","document_id":"1079693","passages":[{"id":"27681","type":"title","text":["Ocular manifestations of juvenile rheumatoid arthritis."],"offsets":[[0,55]]},{"id":"27682","type":"abstract","text":["We followed 210 cases of juvenile rheumatoid arthritis closely for eleven years. Thirty-six of the 210 patients (17.2%) developed iridocyclitis. Iridocyclitis was seen most frequently in young female patients (0 to 4 years) with the monoarticular or pauciatricular form of the arthritis. However, 30% of the patients developed uveitis after 16 years of age. Although 61% of patients had a noncontributory ocular history on entry, 42% had active uveitis on entry. Our approach was effective in detecting uveitis in new cases and exacerbations of uveitis in established cases. Forty-four percent of patients with uveitis had one or more identifiable signs or symptoms, such as red eye, ocular pain, decreased visual acuity, or photophobia, in order of decreasing frequency. Even after early detection and prompt treatment, 41% of cases of uveitis did not respond to more than six months of intensive topical treatment with corticosteroids and mydriatics. Despite this, there was a dramatic decrease in the 50% incidence of blinding complications of uveitis cited in earlier studies. Cataract and band keratopathy occurred in only 22 and 13% of our group, respectively. We used chloroquine or hydroxychloroquine in 173 of 210 cases and found only one case of chorioretinopathy attributable to these drugs. Systemically administered corticosteroids were used in 75 of 210 cases; a significant number of posterior subcapsular cataracts was found. Typical keratoconjunctivitis sicca developed in three of the uveitis cases. This association with uveitis and JRA was not noted previously. Surgical treatment of cataracts, band keratopathy, and glaucoma achieved uniformly discouraging results."],"offsets":[[56,1742]]}],"entities":[{"id":"27683","type":"Disease","text":["juvenile rheumatoid arthritis"],"offsets":[[25,54]],"normalized":[{"db_name":"MESH","db_id":"D001171"}]},{"id":"27684","type":"Disease","text":["juvenile rheumatoid arthritis"],"offsets":[[81,110]],"normalized":[{"db_name":"MESH","db_id":"D001171"}]},{"id":"27685","type":"Disease","text":["iridocyclitis"],"offsets":[[186,199]],"normalized":[{"db_name":"MESH","db_id":"D015863"}]},{"id":"27686","type":"Disease","text":["Iridocyclitis"],"offsets":[[201,214]],"normalized":[{"db_name":"MESH","db_id":"D015863"}]},{"id":"27687","type":"Disease","text":["arthritis"],"offsets":[[333,342]],"normalized":[{"db_name":"MESH","db_id":"D001168"}]},{"id":"27688","type":"Disease","text":["uveitis"],"offsets":[[383,390]],"normalized":[{"db_name":"MESH","db_id":"D014605"}]},{"id":"27689","type":"Disease","text":["uveitis"],"offsets":[[501,508]],"normalized":[{"db_name":"MESH","db_id":"D014605"}]},{"id":"27690","type":"Disease","text":["uveitis"],"offsets":[[559,566]],"normalized":[{"db_name":"MESH","db_id":"D014605"}]},{"id":"27691","type":"Disease","text":["uveitis"],"offsets":[[601,608]],"normalized":[{"db_name":"MESH","db_id":"D014605"}]},{"id":"27692","type":"Disease","text":["uveitis"],"offsets":[[667,674]],"normalized":[{"db_name":"MESH","db_id":"D014605"}]},{"id":"27693","type":"Disease","text":["ocular pain"],"offsets":[[740,751]],"normalized":[{"db_name":"MESH","db_id":"D058447"}]},{"id":"27694","type":"Disease","text":["decreased visual acuity"],"offsets":[[753,776]],"normalized":[{"db_name":"MESH","db_id":"D014786"}]},{"id":"27695","type":"Disease","text":["photophobia"],"offsets":[[781,792]],"normalized":[{"db_name":"MESH","db_id":"D020795"}]},{"id":"27696","type":"Disease","text":["uveitis"],"offsets":[[893,900]],"normalized":[{"db_name":"MESH","db_id":"D014605"}]},{"id":"27697","type":"Chemical","text":["corticosteroids"],"offsets":[[977,992]],"normalized":[{"db_name":"MESH","db_id":"D000305"}]},{"id":"27698","type":"Disease","text":["uveitis"],"offsets":[[1103,1110]],"normalized":[{"db_name":"MESH","db_id":"D014605"}]},{"id":"27699","type":"Disease","text":["Cataract"],"offsets":[[1137,1145]],"normalized":[{"db_name":"MESH","db_id":"D002386"}]},{"id":"27700","type":"Disease","text":["band keratopathy"],"offsets":[[1150,1166]],"normalized":[{"db_name":"MESH","db_id":"C562399"}]},{"id":"27701","type":"Chemical","text":["chloroquine"],"offsets":[[1231,1242]],"normalized":[{"db_name":"MESH","db_id":"D002738"}]},{"id":"27702","type":"Chemical","text":["hydroxychloroquine"],"offsets":[[1246,1264]],"normalized":[{"db_name":"MESH","db_id":"D006886"}]},{"id":"27703","type":"Disease","text":["chorioretinopathy"],"offsets":[[1312,1329]],"normalized":[{"db_name":"MESH","db_id":"D012164"}]},{"id":"27704","type":"Chemical","text":["corticosteroids"],"offsets":[[1385,1400]],"normalized":[{"db_name":"MESH","db_id":"D000305"}]},{"id":"27705","type":"Disease","text":["cataracts"],"offsets":[[1477,1486]],"normalized":[{"db_name":"MESH","db_id":"D002386"}]},{"id":"27706","type":"Disease","text":["keratoconjunctivitis"],"offsets":[[1506,1526]],"normalized":[{"db_name":"MESH","db_id":"D007637"}]},{"id":"27707","type":"Disease","text":["uveitis"],"offsets":[[1559,1566]],"normalized":[{"db_name":"MESH","db_id":"D014605"}]},{"id":"27708","type":"Disease","text":["uveitis"],"offsets":[[1596,1603]],"normalized":[{"db_name":"MESH","db_id":"D014605"}]},{"id":"27709","type":"Disease","text":["cataracts"],"offsets":[[1660,1669]],"normalized":[{"db_name":"MESH","db_id":"D002386"}]},{"id":"27710","type":"Disease","text":["band keratopathy"],"offsets":[[1671,1687]],"normalized":[{"db_name":"MESH","db_id":"C562399"}]},{"id":"27711","type":"Disease","text":["glaucoma"],"offsets":[[1693,1701]],"normalized":[{"db_name":"MESH","db_id":"D005901"}]}],"events":[],"coreferences":[],"relations":[{"id":"27712","type":"CID","arg1_id":"27702","arg2_id":"27703","normalized":[]}]}
{"id":"27713","document_id":"803783","passages":[{"id":"27714","type":"title","text":["Water intoxication associated with oxytocin administration during saline-induced abortion."],"offsets":[[0,90]]},{"id":"27715","type":"abstract","text":["Four cases of water intoxication in connection with oxytocin administration during saline-induced abortions are described. The mechanism of water intoxication is discussed in regard to these cases. Oxytocin administration during midtrimester-induced abortions is advocated only if it can be carried out under careful observations of an alert nursing staff, aware of the symptoms of water intoxication and instructed to watch the diuresis and report such early signs of the syndrome as asthenia, muscular irritability, or headaches. The oxytocin should be given only in Ringers lactate or, alternately, in Ringers lactate and a 5 per cent dextrose and water solutions. The urinary output should be monitored and the oxytocin administration discontinued and the serum electrolytes checked if the urinary output decreases. The oxytocin should not be administered in excess of 36 hours. If the patient has not aborted by then the oxytocin should be discontinued for 10 to 12 hours in order to perform electrolyte determinations and correct any electrolyte imbalance."],"offsets":[[91,1153]]}],"entities":[{"id":"27716","type":"Disease","text":["Water intoxication"],"offsets":[[0,18]],"normalized":[{"db_name":"MESH","db_id":"D014869"}]},{"id":"27717","type":"Chemical","text":["oxytocin"],"offsets":[[35,43]],"normalized":[{"db_name":"MESH","db_id":"D010121"}]},{"id":"27718","type":"Disease","text":["abortion"],"offsets":[[81,89]],"normalized":[{"db_name":"MESH","db_id":"D000031"}]},{"id":"27719","type":"Disease","text":["water 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