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+,number,title,abstract,entities
+0,227508,Naloxone reverses the antihypertensive effect of clonidine.,"In unanesthetized, spontaneously hypertensive rats the decrease in blood pressure and heart rate produced by intravenous clonidine, 5 to 20 micrograms/kg, was inhibited or reversed by nalozone, 0.2 to 2 mg/kg. The hypotensive effect of 100 mg/kg alpha-methyldopa was also partially reversed by naloxone. Naloxone alone did not affect either blood pressure or heart rate. In brain membranes from spontaneously hypertensive rats clonidine, 10(-8) to 10(-5) M, did not influence stereoselective binding of [3H]-naloxone (8 nM), and naloxone, 10(-8) to 10(-4) M, did not influence clonidine-suppressible binding of [3H]-dihydroergocryptine (1 nM). These findings indicate that in spontaneously hypertensive rats the effects of central alpha-adrenoceptor stimulation involve activation of opiate receptors. As naloxone and clonidine do not appear to interact with the same receptor site, the observed functional antagonism suggests the release of an endogenous opiate by clonidine or alpha-methyldopa and the possible role of the opiate in the central control of sympathetic tone.","[{'text': 'Naloxone', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D009270'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 49, 'end': 58, 'mesh': 'D003000'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 93, 'end': 105, 'mesh': 'D006973'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 181, 'end': 190, 'mesh': 'D003000'}, {'text': 'nalozone', 'type': 'Chemical', 'start': 244, 'end': 252, 'mesh': '-1'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 274, 'end': 285, 'mesh': 'D007022'}, {'text': 'alpha-methyldopa', 'type': 'Chemical', 'start': 306, 'end': 322, 'mesh': 'D008750'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 354, 'end': 362, 'mesh': 'D009270'}, {'text': 'Naloxone', 'type': 'Chemical', 'start': 364, 'end': 372, 'mesh': 'D009270'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 469, 'end': 481, 'mesh': 'D006973'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 487, 'end': 496, 'mesh': 'D003000'}, {'text': '[3H]-naloxone', 'type': 'Chemical', 'start': 563, 'end': 576, 'mesh': '-1'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 589, 'end': 597, 'mesh': 'D009270'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 637, 'end': 646, 'mesh': 'D003000'}, {'text': '[3H]-dihydroergocryptine', 'type': 'Chemical', 'start': 671, 'end': 695, 'mesh': '-1'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 750, 'end': 762, 'mesh': 'D006973'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 865, 'end': 873, 'mesh': 'D009270'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 878, 'end': 887, 'mesh': 'D003000'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 1026, 'end': 1035, 'mesh': 'D003000'}, {'text': 'alpha-methyldopa', 'type': 'Chemical', 'start': 1039, 'end': 1055, 'mesh': 'D008750'}]"
+1,354896,Lidocaine-induced cardiac asystole.,"Intravenous administration of a single 50-mg bolus of lidocaine in a 67-year-old man resulted in profound depression of the activity of the sinoatrial and atrioventricular nodal pacemakers. The patient had no apparent associated conditions which might have predisposed him to the development of bradyarrhythmias; and, thus, this probably represented a true idiosyncrasy to lidocaine.","[{'text': 'Lidocaine', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D008012'}, {'text': 'cardiac asystole', 'type': 'Disease', 'start': 18, 'end': 34, 'mesh': 'D006323'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 90, 'end': 99, 'mesh': 'D008012'}, {'text': 'depression', 'type': 'Disease', 'start': 142, 'end': 152, 'mesh': 'D003866'}, {'text': 'bradyarrhythmias', 'type': 'Disease', 'start': 331, 'end': 347, 'mesh': 'D001919'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 409, 'end': 418, 'mesh': 'D008012'}]"
+2,435349,Suxamethonium infusion rate and observed fasciculations. A dose-response study.,"Suxamethonium chloride (Sch) was administered i.v. to 36 adult males at six rates: 0.25 mg s-1 to 20 mg s-1. The infusion was discontinued either when there was no muscular response to tetanic stimulation of the ulnar nerve or when Sch 120 mg was exceeded. Six additional patients received a 30-mg i.v. bolus dose. Fasciculations in six areas of the body were scored from 0 to 3 and summated as a total fasciculation score. The times to first fasciculation, twitch suppression and tetanus suppression were inversely related to the infusion rates. Fasciculations in the six areas and the total fasciculation score were related directly to the rate of infusion. Total fasciculation scores in the 30-mg bolus group and the 5-mg s-1 and 20-mg s-1 infusion groups were not significantly different.","[{'text': 'Suxamethonium', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'D013390'}, {'text': 'fasciculations', 'type': 'Disease', 'start': 41, 'end': 55, 'mesh': 'D005207'}, {'text': 'Suxamethonium chloride', 'type': 'Chemical', 'start': 80, 'end': 102, 'mesh': 'D013390'}, {'text': 'Sch', 'type': 'Chemical', 'start': 104, 'end': 107, 'mesh': 'D013390'}, {'text': 'tetanic', 'type': 'Disease', 'start': 265, 'end': 272, 'mesh': 'D013746'}, {'text': 'Sch', 'type': 'Chemical', 'start': 312, 'end': 315, 'mesh': 'D013390'}, {'text': 'Fasciculations', 'type': 'Disease', 'start': 395, 'end': 409, 'mesh': 'D005207'}, {'text': 'fasciculation', 'type': 'Disease', 'start': 483, 'end': 496, 'mesh': 'D005207'}, {'text': 'fasciculation', 'type': 'Disease', 'start': 523, 'end': 536, 'mesh': 'D005207'}, {'text': 'twitch', 'type': 'Disease', 'start': 538, 'end': 544, 'mesh': 'D013746'}, {'text': 'tetanus', 'type': 'Disease', 'start': 561, 'end': 568, 'mesh': 'D013746'}, {'text': 'Fasciculations', 'type': 'Disease', 'start': 627, 'end': 641, 'mesh': 'D005207'}, {'text': 'fasciculation', 'type': 'Disease', 'start': 673, 'end': 686, 'mesh': 'D005207'}, {'text': 'fasciculation', 'type': 'Disease', 'start': 746, 'end': 759, 'mesh': 'D005207'}]"
+3,603022,"Galanthamine hydrobromide, a longer acting anticholinesterase drug, in the treatment of the central effects of scopolamine (Hyoscine).","Galanthamine hydrobromide, an anticholinesterase drug capable of penetrating the blood-brain barrier, was used in a patient demonstrating central effects of scopolamine (hyoscine) overdosage. It is longer acting than physostigmine and is used in anaesthesia to reverse the non-depolarizing neuromuscular block. However, studies into the dose necessary to combating scopolamine intoxication are indicated.","[{'text': 'Galanthamine hydrobromide', 'type': 'Chemical', 'start': 0, 'end': 25, 'mesh': 'D005702'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 111, 'end': 122, 'mesh': 'D012601'}, {'text': 'Hyoscine', 'type': 'Chemical', 'start': 124, 'end': 132, 'mesh': 'D012601'}, {'text': 'Galanthamine hydrobromide', 'type': 'Chemical', 'start': 135, 'end': 160, 'mesh': 'D005702'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 292, 'end': 303, 'mesh': 'D012601'}, {'text': 'hyoscine', 'type': 'Chemical', 'start': 305, 'end': 313, 'mesh': 'D012601'}, {'text': 'overdosage', 'type': 'Disease', 'start': 315, 'end': 325, 'mesh': 'D062787'}, {'text': 'physostigmine', 'type': 'Chemical', 'start': 352, 'end': 365, 'mesh': 'D010830'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 500, 'end': 511, 'mesh': 'D012601'}]"
+4,1378968,Effects of uninephrectomy and high protein feeding on lithium-induced chronic renal failure in rats.,"Rats with lithium-induced nephropathy were subjected to high protein (HP) feeding, uninephrectomy (NX) or a combination of these, in an attempt to induce glomerular hyperfiltration and further progression of renal failure. Newborn female Wistar rats were fed a lithium-containing diet (50 mmol/kg) for 8 weeks and then randomized to normal diet, HP diet (40 vs. 19%), NX or HP+NX for another 8 weeks. Corresponding non-lithium pretreated groups were generated. When comparing all lithium treated versus non-lithium-treated groups, lithium caused a reduction in glomerular filtration rate (GFR) without significant changes in effective renal plasma flow (as determined by a marker secreted into the proximal tubules) or lithium clearance. Consequently, lithium pretreatment caused a fall in filtration fraction and an increase in fractional Li excretion. Lithium also caused proteinuria and systolic hypertension in absence of glomerulosclerosis. HP failed to accentuante progression of renal failure and in fact tended to increase GFR and decrease plasma creatinine levels in lithium pretreated rats. NX caused an additive deterioration in GFR which, however, was ameliorated by HP. NX+HP caused a further rise in blood pressure in Li-pretreated rats. The results indicate that Li-induced nephropathy, even when the GFR is only modestly reduced, is associated with proteinuria and arterial systolic hypertension. In this model of chronic renal failure the decline in GFR is not accompanied by a corresponding fall in effective renal plasma flow, which may be the functional expression of the formation of nonfiltrating atubular glomeruli. The fractional reabsorption of tubular fluid by the proximal tubules is reduced, leaving the distal delivery unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)","[{'text': 'lithium', 'type': 'Chemical', 'start': 54, 'end': 61, 'mesh': 'D008094'}, {'text': 'chronic renal failure', 'type': 'Disease', 'start': 70, 'end': 91, 'mesh': 'D007676'}, {'text': 'lithium', 'type': 'Chemical', 'start': 111, 'end': 118, 'mesh': 'D008094'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 127, 'end': 138, 'mesh': 'D007674'}, {'text': 'renal failure', 'type': 'Disease', 'start': 309, 'end': 322, 'mesh': 'D051437'}, {'text': 'lithium', 'type': 'Chemical', 'start': 362, 'end': 369, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 520, 'end': 527, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 581, 'end': 588, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 608, 'end': 615, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 632, 'end': 639, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 820, 'end': 827, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 853, 'end': 860, 'mesh': 'D008094'}, {'text': 'Li', 'type': 'Chemical', 'start': 941, 'end': 943, 'mesh': 'D008094'}, {'text': 'Lithium', 'type': 'Chemical', 'start': 955, 'end': 962, 'mesh': 'D008094'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 975, 'end': 986, 'mesh': 'D011507'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1000, 'end': 1012, 'mesh': 'D006973'}, {'text': 'glomerulosclerosis', 'type': 'Disease', 'start': 1027, 'end': 1045, 'mesh': 'D005921'}, {'text': 'renal failure', 'type': 'Disease', 'start': 1087, 'end': 1100, 'mesh': 'D051437'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1156, 'end': 1166, 'mesh': 'D003404'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1177, 'end': 1184, 'mesh': 'D008094'}, {'text': 'Li', 'type': 'Chemical', 'start': 1333, 'end': 1335, 'mesh': 'D008094'}, {'text': 'Li', 'type': 'Chemical', 'start': 1379, 'end': 1381, 'mesh': 'D008094'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1390, 'end': 1401, 'mesh': 'D007674'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1466, 'end': 1477, 'mesh': 'D011507'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1500, 'end': 1512, 'mesh': 'D006973'}, {'text': 'chronic renal failure', 'type': 'Disease', 'start': 1531, 'end': 1552, 'mesh': 'D007676'}]"
+5,1420741,Treatment of Crohn's disease with fusidic acid: an antibiotic with immunosuppressive properties similar to cyclosporin.,"Fusidic acid is an antibiotic with T-cell specific immunosuppressive effects similar to those of cyclosporin. Because of the need for the development of new treatments for Crohn's disease, a pilot study was undertaken to estimate the pharmacodynamics and tolerability of fusidic acid treatment in chronic active, therapy-resistant patients. Eight Crohn's disease patients were included. Fusidic acid was administered orally in a dose of 500 mg t.d.s. and the treatment was planned to last 8 weeks. The disease activity was primarily measured by a modified individual grading score. Five of 8 patients (63%) improved during fusidic acid treatment: 3 at two weeks and 2 after four weeks. There were no serious clinical side effects, but dose reduction was required in two patients because of nausea. Biochemically, an increase in alkaline phosphatases was noted in 5 of 8 cases (63%), and the greatest increases were seen in those who had elevated levels prior to treatment. All reversed to pre-treatment levels after cessation of treatment. The results of this pilot study suggest that fusidic acid may be of benefit in selected chronic active Crohn's disease patients in whom conventional treatment is ineffective. Because there seems to exist a scientific rationale for the use of fusidic acid at the cytokine level in inflammatory bowel disease, we suggest that the role of this treatment should be further investigated.","[{'text': ""Crohn's disease"", 'type': 'Disease', 'start': 13, 'end': 28, 'mesh': 'D003424'}, {'text': 'fusidic acid', 'type': 'Chemical', 'start': 34, 'end': 46, 'mesh': 'D005672'}, {'text': 'cyclosporin', 'type': 'Chemical', 'start': 107, 'end': 118, 'mesh': 'D016572'}, {'text': 'cyclosporin', 'type': 'Chemical', 'start': 217, 'end': 228, 'mesh': 'D016572'}, {'text': ""Crohn's disease"", 'type': 'Disease', 'start': 292, 'end': 307, 'mesh': 'D003424'}, {'text': 'fusidic acid', 'type': 'Chemical', 'start': 391, 'end': 403, 'mesh': 'D005672'}, {'text': ""Crohn's disease"", 'type': 'Disease', 'start': 467, 'end': 482, 'mesh': 'D003424'}, {'text': 'Fusidic acid', 'type': 'Chemical', 'start': 507, 'end': 519, 'mesh': 'D005672'}, {'text': 'fusidic acid', 'type': 'Chemical', 'start': 743, 'end': 755, 'mesh': 'D005672'}, {'text': 'nausea', 'type': 'Disease', 'start': 910, 'end': 916, 'mesh': 'D009325'}, {'text': 'fusidic acid', 'type': 'Chemical', 'start': 1205, 'end': 1217, 'mesh': 'D005672'}, {'text': ""Crohn's disease"", 'type': 'Disease', 'start': 1263, 'end': 1278, 'mesh': 'D003424'}, {'text': 'fusidic acid', 'type': 'Chemical', 'start': 1402, 'end': 1414, 'mesh': 'D005672'}, {'text': 'inflammatory bowel disease', 'type': 'Disease', 'start': 1440, 'end': 1466, 'mesh': 'D015212'}]"
+6,1601297,Electrocardiographic evidence of myocardial injury in psychiatrically hospitalized cocaine abusers.,"The electrocardiograms (ECG) of 99 cocaine-abusing patients were compared with the ECGs of 50 schizophrenic controls. Eleven of the cocaine abusers and none of the controls had ECG evidence of significant myocardial injury defined as myocardial infarction, ischemia, and bundle branch block.","[{'text': 'myocardial injury', 'type': 'Disease', 'start': 33, 'end': 50, 'mesh': 'D009202'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 83, 'end': 90, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 135, 'end': 142, 'mesh': 'D003042'}, {'text': 'schizophrenic', 'type': 'Disease', 'start': 194, 'end': 207, 'mesh': 'D012559'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 232, 'end': 239, 'mesh': 'D003042'}, {'text': 'myocardial injury', 'type': 'Disease', 'start': 305, 'end': 322, 'mesh': 'D009202'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 334, 'end': 355, 'mesh': 'D009203'}, {'text': 'ischemia', 'type': 'Disease', 'start': 357, 'end': 365, 'mesh': 'D007511'}, {'text': 'bundle branch block', 'type': 'Disease', 'start': 371, 'end': 390, 'mesh': 'D002037'}]"
+7,1967484,Sulpiride-induced tardive dystonia.,"Sulpiride is a selective D2-receptor antagonist with antipsychotic and antidepressant properties. Although initially thought to be free of extrapyramidal side effects, sulpiride-induced tardive dyskinesia and parkinsonism have been reported occasionally. We studied a 37-year-old man who developed persistent segmental dystonia within 2 months after starting sulpiride therapy. We could not find any previous reports of sulpiride-induced tardive dystonia.","[{'text': 'Sulpiride', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D013469'}, {'text': 'tardive dystonia', 'type': 'Disease', 'start': 18, 'end': 34, 'mesh': 'D004421'}, {'text': 'Sulpiride', 'type': 'Chemical', 'start': 36, 'end': 45, 'mesh': 'D013469'}, {'text': 'antidepressant', 'type': 'Chemical', 'start': 107, 'end': 121, 'mesh': 'D000928'}, {'text': 'sulpiride', 'type': 'Chemical', 'start': 204, 'end': 213, 'mesh': 'D013469'}, {'text': 'tardive dyskinesia', 'type': 'Disease', 'start': 222, 'end': 240, 'mesh': 'D004409'}, {'text': 'parkinsonism', 'type': 'Disease', 'start': 245, 'end': 257, 'mesh': 'D010302'}, {'text': 'dystonia', 'type': 'Disease', 'start': 355, 'end': 363, 'mesh': 'D004421'}, {'text': 'sulpiride', 'type': 'Chemical', 'start': 395, 'end': 404, 'mesh': 'D013469'}, {'text': 'sulpiride', 'type': 'Chemical', 'start': 456, 'end': 465, 'mesh': 'D013469'}, {'text': 'tardive dystonia', 'type': 'Disease', 'start': 474, 'end': 490, 'mesh': 'D004421'}]"
+8,2234245,Ocular and auditory toxicity in hemodialyzed patients receiving desferrioxamine.,"During an 18-month period of study 41 hemodialyzed patients receiving desferrioxamine (10-40 mg/kg BW/3 times weekly) for the first time were monitored for detection of audiovisual toxicity. 6 patients presented clinical symptoms of visual or auditory toxicity. Moreover, detailed ophthalmologic and audiologic studies disclosed abnormalities in 7 more asymptomatic patients. Visual toxicity was of retinal origin and was characterized by a tritan-type dyschromatopsy, sometimes associated with a loss of visual acuity and pigmentary retinal deposits. Auditory toxicity was characterized by a mid- to high-frequency neurosensorial hearing loss and the lesion was of the cochlear type. Desferrioxamine withdrawal resulted in a complete recovery of visual function in 1 patient and partial recovery in 3, and a complete reversal of hearing loss in 3 patients and partial recovery in 3. This toxicity appeared in patients receiving the higher doses of desferrioxamine or coincided with the normalization of ferritin or aluminium serum levels. The data indicate that audiovisual toxicity is not an infrequent complication in hemodialyzed patients receiving desferrioxamine. Periodical audiovisual monitoring should be performed on hemodialyzed patients receiving the drug in order to detect adverse effects as early as possible.","[{'text': 'desferrioxamine', 'type': 'Chemical', 'start': 64, 'end': 79, 'mesh': 'D003676'}, {'text': 'desferrioxamine', 'type': 'Chemical', 'start': 151, 'end': 166, 'mesh': 'D003676'}, {'text': 'audiovisual toxicity', 'type': 'Disease', 'start': 250, 'end': 270, 'mesh': 'D014786|D006311'}, {'text': 'Visual toxicity', 'type': 'Disease', 'start': 457, 'end': 472, 'mesh': 'D014786'}, {'text': 'dyschromatopsy', 'type': 'Disease', 'start': 534, 'end': 548, 'mesh': '-1'}, {'text': 'a loss of visual acuity', 'type': 'Disease', 'start': 576, 'end': 599, 'mesh': 'D014786'}, {'text': 'pigmentary retinal deposits', 'type': 'Disease', 'start': 604, 'end': 631, 'mesh': 'D012164'}, {'text': 'Auditory toxicity', 'type': 'Disease', 'start': 633, 'end': 650, 'mesh': 'D006311'}, {'text': 'neurosensorial hearing loss', 'type': 'Disease', 'start': 697, 'end': 724, 'mesh': 'D006319'}, {'text': 'Desferrioxamine', 'type': 'Chemical', 'start': 766, 'end': 781, 'mesh': 'D003676'}, {'text': 'hearing loss', 'type': 'Disease', 'start': 911, 'end': 923, 'mesh': 'D034381'}, {'text': 'toxicity', 'type': 'Disease', 'start': 970, 'end': 978, 'mesh': 'D064420'}, {'text': 'desferrioxamine', 'type': 'Chemical', 'start': 1030, 'end': 1045, 'mesh': 'D003676'}, {'text': 'aluminium', 'type': 'Chemical', 'start': 1097, 'end': 1106, 'mesh': '-1'}, {'text': 'audiovisual toxicity', 'type': 'Disease', 'start': 1144, 'end': 1164, 'mesh': 'D014786|D006311'}, {'text': 'desferrioxamine', 'type': 'Chemical', 'start': 1234, 'end': 1249, 'mesh': 'D003676'}]"
+9,2385256,Myasthenia gravis presenting as weakness after magnesium administration.,"We studied a patient with no prior history of neuromuscular disease who became virtually quadriplegic after parenteral magnesium administration for preeclampsia. The serum magnesium concentration was 3.0 mEq/L, which is usually well tolerated. The magnesium was stopped and she recovered over a few days. While she was weak, 2-Hz repetitive stimulation revealed a decrement without significant facilitation at rapid rates or after exercise, suggesting postsynaptic neuromuscular blockade. After her strength returned, repetitive stimulation was normal, but single fiber EMG revealed increased jitter and blocking. Her acetylcholine receptor antibody level was markedly elevated. Although paralysis after magnesium administration has been described in patients with known myasthenia gravis, it has not previously been reported to be the initial or only manifestation of the disease. Patients who are unusually sensitive to the neuromuscular effects of magnesium should be suspected of having an underlying disorder of neuromuscular transmission.","[{'text': 'Myasthenia gravis', 'type': 'Disease', 'start': 0, 'end': 17, 'mesh': 'D009157'}, {'text': 'magnesium', 'type': 'Chemical', 'start': 47, 'end': 56, 'mesh': 'D008274'}, {'text': 'neuromuscular disease', 'type': 'Disease', 'start': 119, 'end': 140, 'mesh': 'D009468'}, {'text': 'quadriplegic', 'type': 'Disease', 'start': 162, 'end': 174, 'mesh': 'D011782'}, {'text': 'magnesium', 'type': 'Chemical', 'start': 192, 'end': 201, 'mesh': 'D008274'}, {'text': 'preeclampsia', 'type': 'Disease', 'start': 221, 'end': 233, 'mesh': 'D011225'}, {'text': 'magnesium', 'type': 'Chemical', 'start': 245, 'end': 254, 'mesh': 'D008274'}, {'text': 'magnesium', 'type': 'Chemical', 'start': 321, 'end': 330, 'mesh': 'D008274'}, {'text': 'postsynaptic neuromuscular blockade', 'type': 'Disease', 'start': 525, 'end': 560, 'mesh': 'D009468'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 691, 'end': 704, 'mesh': 'D000109'}, {'text': 'paralysis', 'type': 'Disease', 'start': 761, 'end': 770, 'mesh': 'D010243'}, {'text': 'magnesium', 'type': 'Chemical', 'start': 777, 'end': 786, 'mesh': 'D008274'}, {'text': 'myasthenia gravis', 'type': 'Disease', 'start': 844, 'end': 861, 'mesh': 'D009157'}, {'text': 'magnesium', 'type': 'Chemical', 'start': 1024, 'end': 1033, 'mesh': 'D008274'}, {'text': 'disorder of neuromuscular transmission', 'type': 'Disease', 'start': 1078, 'end': 1116, 'mesh': 'D020511'}]"
+10,2505783,Chloroacetaldehyde and its contribution to urotoxicity during treatment with cyclophosphamide or ifosfamide. An experimental study/short communication.,"Based on clinical data, indicating that chloroacetaldehyde (CAA) is an important metabolite of oxazaphosphorine cytostatics, an experimental study was carried out in order to elucidate the role of CAA in the development of hemorrhagic cystitis. The data demonstrate that CAA after i.v. administration does not contribute to bladder damage. When instilled directly into the bladder, CAA exerts urotoxic effects, it is, however, susceptible to detoxification with mesna.","[{'text': 'Chloroacetaldehyde', 'type': 'Chemical', 'start': 0, 'end': 18, 'mesh': 'C004656'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 77, 'end': 93, 'mesh': 'D003520'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 97, 'end': 107, 'mesh': 'D007069'}, {'text': 'chloroacetaldehyde', 'type': 'Chemical', 'start': 192, 'end': 210, 'mesh': 'C004656'}, {'text': 'CAA', 'type': 'Chemical', 'start': 212, 'end': 215, 'mesh': 'C004656'}, {'text': 'CAA', 'type': 'Chemical', 'start': 349, 'end': 352, 'mesh': 'C004656'}, {'text': 'CAA', 'type': 'Chemical', 'start': 423, 'end': 426, 'mesh': 'C004656'}, {'text': 'bladder damage', 'type': 'Disease', 'start': 476, 'end': 490, 'mesh': 'D001745'}, {'text': 'CAA', 'type': 'Chemical', 'start': 534, 'end': 537, 'mesh': 'C004656'}, {'text': 'mesna', 'type': 'Chemical', 'start': 614, 'end': 619, 'mesh': 'D015080'}]"
+11,2515254,Source of pain and primitive dysfunction in migraine: an identical site?,"Twenty common migraine patients received a one sided frontotemporal application of nitroglycerin (10 patients) or placebo ointment (10 patients) in a double blind study. Early onset migraine attacks were induced by nitroglycerin in seven out of 10 patients versus no patient in the placebo group. Subsequently 20 migraine patients, who developed an early onset attack with frontotemporal nitroglycerin, received the drug in a second induction test at other body areas. No early onset migraine was observed. Thus the migraine-inducing effect of nitroglycerin seems to depend on direct stimulation of the habitual site of pain, suggesting that the frontotemporal region is of crucial importance in the development of a migraine crisis. This is not consistent with a CNS origin of migraine attack.","[{'text': 'pain', 'type': 'Disease', 'start': 10, 'end': 14, 'mesh': 'D010146'}, {'text': 'migraine', 'type': 'Disease', 'start': 44, 'end': 52, 'mesh': 'D008881'}, {'text': 'migraine', 'type': 'Disease', 'start': 87, 'end': 95, 'mesh': 'D008881'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 156, 'end': 169, 'mesh': 'D005996'}, {'text': 'migraine', 'type': 'Disease', 'start': 255, 'end': 263, 'mesh': 'D008881'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 288, 'end': 301, 'mesh': 'D005996'}, {'text': 'migraine', 'type': 'Disease', 'start': 386, 'end': 394, 'mesh': 'D008881'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 461, 'end': 474, 'mesh': 'D005996'}, {'text': 'migraine', 'type': 'Disease', 'start': 557, 'end': 565, 'mesh': 'D008881'}, {'text': 'migraine', 'type': 'Disease', 'start': 589, 'end': 597, 'mesh': 'D008881'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 617, 'end': 630, 'mesh': 'D005996'}, {'text': 'pain', 'type': 'Disease', 'start': 693, 'end': 697, 'mesh': 'D010146'}, {'text': 'migraine', 'type': 'Disease', 'start': 790, 'end': 798, 'mesh': 'D008881'}, {'text': 'migraine', 'type': 'Disease', 'start': 851, 'end': 859, 'mesh': 'D008881'}]"
+12,2572625,Clotiazepam-induced acute hepatitis.,"We report the case of a patient who developed acute hepatitis with extensive hepatocellular necrosis, 7 months after the onset of administration of clotiazepam, a thienodiazepine derivative. Clotiazepam withdrawal was followed by prompt recovery. The administration of several benzodiazepines, chemically related to clotiazepam, did not interfere with recovery and did not induce any relapse of hepatitis. This observation shows that clotiazepam can induce acute hepatitis and suggests that there is no cross hepatotoxicity between clotiazepam and several benzodiazepines.","[{'text': 'Clotiazepam', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'C084599'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 26, 'end': 35, 'mesh': 'D056486'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 89, 'end': 98, 'mesh': 'D056486'}, {'text': 'extensive hepatocellular necrosis', 'type': 'Disease', 'start': 104, 'end': 137, 'mesh': 'D047508'}, {'text': 'clotiazepam', 'type': 'Chemical', 'start': 185, 'end': 196, 'mesh': 'C084599'}, {'text': 'thienodiazepine', 'type': 'Chemical', 'start': 200, 'end': 215, 'mesh': 'C013295'}, {'text': 'Clotiazepam', 'type': 'Chemical', 'start': 228, 'end': 239, 'mesh': 'C084599'}, {'text': 'benzodiazepines', 'type': 'Chemical', 'start': 314, 'end': 329, 'mesh': 'D001569'}, {'text': 'clotiazepam', 'type': 'Chemical', 'start': 353, 'end': 364, 'mesh': 'C084599'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 432, 'end': 441, 'mesh': 'D056486'}, {'text': 'clotiazepam', 'type': 'Chemical', 'start': 471, 'end': 482, 'mesh': 'C084599'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 500, 'end': 509, 'mesh': 'D056486'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 546, 'end': 560, 'mesh': 'D056486'}, {'text': 'clotiazepam', 'type': 'Chemical', 'start': 569, 'end': 580, 'mesh': 'C084599'}, {'text': 'benzodiazepines', 'type': 'Chemical', 'start': 593, 'end': 608, 'mesh': 'D001569'}]"
+13,2632720,Arterial hypertension as a complication of prolonged ketoconazole treatment.,"Two of 14 patients with Cushing's syndrome treated on a long-term basis with ketoconazole developed sustained hypertension. In both cases normal plasma and urinary free cortisol levels had been achieved following ketoconazole therapy, yet continuous blood pressure monitoring demonstrated hypertension 31 (patient 1) and 52 weeks (patient 2) after treatment. In patient 1, plasma levels of deoxycorticosterone and 11-deoxycortisol were elevated. In patient 2, in addition to an increase in both deoxycorticosterone and 11-deoxycortisol levels, plasma aldosterone values were raised, with a concomitant suppression of renin levels. Our findings show that long-term treatment with high doses of ketoconazole may induce enzyme blockade leading to mineralocorticoid-related hypertension.","[{'text': 'hypertension', 'type': 'Disease', 'start': 9, 'end': 21, 'mesh': 'D006973'}, {'text': 'ketoconazole', 'type': 'Chemical', 'start': 53, 'end': 65, 'mesh': 'D007654'}, {'text': ""Cushing's syndrome"", 'type': 'Disease', 'start': 101, 'end': 119, 'mesh': 'D003480'}, {'text': 'ketoconazole', 'type': 'Chemical', 'start': 154, 'end': 166, 'mesh': 'D007654'}, {'text': 'hypertension', 'type': 'Disease', 'start': 187, 'end': 199, 'mesh': 'D006973'}, {'text': 'cortisol', 'type': 'Chemical', 'start': 246, 'end': 254, 'mesh': 'D006854'}, {'text': 'ketoconazole', 'type': 'Chemical', 'start': 290, 'end': 302, 'mesh': 'D007654'}, {'text': 'hypertension', 'type': 'Disease', 'start': 366, 'end': 378, 'mesh': 'D006973'}, {'text': 'deoxycorticosterone', 'type': 'Chemical', 'start': 467, 'end': 486, 'mesh': 'D003900'}, {'text': '11-deoxycortisol', 'type': 'Chemical', 'start': 491, 'end': 507, 'mesh': 'D003350'}, {'text': 'deoxycorticosterone', 'type': 'Chemical', 'start': 572, 'end': 591, 'mesh': 'D003900'}, {'text': '11-deoxycortisol', 'type': 'Chemical', 'start': 596, 'end': 612, 'mesh': 'D003350'}, {'text': 'aldosterone', 'type': 'Chemical', 'start': 628, 'end': 639, 'mesh': 'D000450'}, {'text': 'ketoconazole', 'type': 'Chemical', 'start': 770, 'end': 782, 'mesh': 'D007654'}, {'text': 'hypertension', 'type': 'Disease', 'start': 847, 'end': 859, 'mesh': 'D006973'}]"
+14,2670794,Effects of an inhibitor of angiotensin converting enzyme (Captopril) on pulmonary and renal insufficiency due to intravascular coagulation in the rat.,"Induction of intravascular coagulation and inhibition of fibrinolysis by injection of thrombin and tranexamic acid (AMCA) in the rat gives rise to pulmonary and renal insufficiency resembling that occurring after trauma or sepsis in man. Injection of Captopril (1 mg/kg), an inhibitor of angiotensin converting enzyme (ACE), reduced both pulmonary and renal insufficiency in this rat model. The lung weights were lower and PaO2 was improved in rats given this enzyme-blocking agent. The contents of albumin in the lungs were not changed, indicating that Captopril did not influence the extravasation of protein. Renal damage as reflected by an increase in serum urea and in kidney weight was prevented by Captopril. The amount of fibrin in the kidneys was also considerably lower than in animals which received thrombin and AMCA alone. It is suggested that the effects of Captopril on the lungs may be attributable to a vasodilatory effect due to a reduction in the circulating level of Angiotension II and an increase in prostacyclin (secondary to an increase in bradykinin). Captopril may, by the same mechanism, reduce the increase in glomerular filtration that is known to occur after an injection of thrombin, thereby diminishing the aggregation of fibrin monomers in the glomeruli, with the result that less fibrin will be deposited and thus less kidney damage will be produced.","[{'text': 'angiotensin', 'type': 'Chemical', 'start': 27, 'end': 38, 'mesh': 'D000809'}, {'text': 'Captopril', 'type': 'Chemical', 'start': 58, 'end': 67, 'mesh': 'D002216'}, {'text': 'intravascular coagulation', 'type': 'Disease', 'start': 113, 'end': 138, 'mesh': 'D004211'}, {'text': 'intravascular coagulation', 'type': 'Disease', 'start': 164, 'end': 189, 'mesh': 'D004211'}, {'text': 'tranexamic acid', 'type': 'Chemical', 'start': 250, 'end': 265, 'mesh': 'D014148'}, {'text': 'AMCA', 'type': 'Chemical', 'start': 267, 'end': 271, 'mesh': 'D014148'}, {'text': 'trauma', 'type': 'Disease', 'start': 364, 'end': 370, 'mesh': 'D014947'}, {'text': 'sepsis', 'type': 'Disease', 'start': 374, 'end': 380, 'mesh': 'D018805'}, {'text': 'Captopril', 'type': 'Chemical', 'start': 402, 'end': 411, 'mesh': 'D002216'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 439, 'end': 450, 'mesh': 'D000809'}, {'text': 'Captopril', 'type': 'Chemical', 'start': 705, 'end': 714, 'mesh': 'D002216'}, {'text': 'Renal damage', 'type': 'Disease', 'start': 763, 'end': 775, 'mesh': 'D007674'}, {'text': 'urea', 'type': 'Chemical', 'start': 813, 'end': 817, 'mesh': 'D014508'}, {'text': 'Captopril', 'type': 'Chemical', 'start': 856, 'end': 865, 'mesh': 'D002216'}, {'text': 'AMCA', 'type': 'Chemical', 'start': 975, 'end': 979, 'mesh': 'D014148'}, {'text': 'Captopril', 'type': 'Chemical', 'start': 1023, 'end': 1032, 'mesh': 'D002216'}, {'text': 'Angiotension II', 'type': 'Chemical', 'start': 1138, 'end': 1153, 'mesh': 'D000804'}, {'text': 'prostacyclin', 'type': 'Chemical', 'start': 1173, 'end': 1185, 'mesh': 'D011464'}, {'text': 'bradykinin', 'type': 'Chemical', 'start': 1215, 'end': 1225, 'mesh': 'D001920'}, {'text': 'Captopril', 'type': 'Chemical', 'start': 1228, 'end': 1237, 'mesh': 'D002216'}, {'text': 'kidney damage', 'type': 'Disease', 'start': 1504, 'end': 1517, 'mesh': 'D007674'}]"
+15,2696505,A randomized comparison of labetalol and nitroprusside for induced hypotension.,"In a randomized study, labetalol-induced hypotension and nitroprusside-induced hypotension were compared in 20 patients (10 in each group) scheduled for major orthopedic procedures. Each patient was subjected to an identical anesthetic protocol and similar drug-induced reductions in mean arterial blood pressure (BP) (50 to 55 mmHg). Nitroprusside infusion was associated with a significant (p less than 0.05) increase in heart rate and cardiac output; rebound hypertension was observed in three patients after discontinuation of nitroprusside. Labetalol administration was not associated with any of these findings. Arterial PO2 decreased in both groups. It was concluded that labetalol offers advantages over nitroprusside.","[{'text': 'labetalol', 'type': 'Chemical', 'start': 27, 'end': 36, 'mesh': 'D007741'}, {'text': 'nitroprusside', 'type': 'Chemical', 'start': 41, 'end': 54, 'mesh': 'D009599'}, {'text': 'hypotension', 'type': 'Disease', 'start': 67, 'end': 78, 'mesh': 'D007022'}, {'text': 'labetalol', 'type': 'Chemical', 'start': 103, 'end': 112, 'mesh': 'D007741'}, {'text': 'hypotension', 'type': 'Disease', 'start': 121, 'end': 132, 'mesh': 'D007022'}, {'text': 'nitroprusside', 'type': 'Chemical', 'start': 137, 'end': 150, 'mesh': 'D009599'}, {'text': 'hypotension', 'type': 'Disease', 'start': 159, 'end': 170, 'mesh': 'D007022'}, {'text': 'reductions in mean arterial blood pressure', 'type': 'Disease', 'start': 350, 'end': 392, 'mesh': 'D007022'}, {'text': 'increase in heart rate and cardiac output', 'type': 'Disease', 'start': 491, 'end': 532, 'mesh': 'D016534'}, {'text': 'hypertension', 'type': 'Disease', 'start': 542, 'end': 554, 'mesh': 'D006973'}, {'text': 'nitroprusside', 'type': 'Chemical', 'start': 611, 'end': 624, 'mesh': 'D009599'}, {'text': 'Labetalol', 'type': 'Chemical', 'start': 626, 'end': 635, 'mesh': 'D007741'}, {'text': 'PO2', 'type': 'Chemical', 'start': 707, 'end': 710, 'mesh': 'C093415'}, {'text': 'labetalol', 'type': 'Chemical', 'start': 759, 'end': 768, 'mesh': 'D007741'}, {'text': 'nitroprusside', 'type': 'Chemical', 'start': 792, 'end': 805, 'mesh': 'D009599'}]"
+16,2924746,"Chronic carbamazepine treatment in the rat: efficacy, toxicity, and effect on plasma and tissue folate concentrations.","Folate depletion has often been a problem in chronic antiepileptic drug (AED) therapy. Carbamazepine (CBZ), a commonly used AED, has been implicated in some clinical studies. A rat model was developed to examine the effects of chronic CBZ treatment on folate concentrations in the rat. In the course of developing this model, a common vehicle, propylene glycol, by itself in high doses, was found to exhibit protective properties against induced seizures and inhibited weight gain. Seizures induced by hexafluorodiethyl ether (HFDE) were also found to be a more sensitive measure of protection by CBZ than seizures induced by maximal electroshock (MES). Oral administration of CBZ as an aqueous suspension every 8 h at a dose of 250 mg/kg was continuously protective against HFDE-induced seizures and was minimally toxic as measured by weight gain over 8 weeks of treatment. The CBZ levels measured in plasma and brain of these animals, however, were below those normally considered protective. This treatment with CBZ had no apparent adverse effect on folate concentrations in the rat, and, indeed, the folate concentration increased in liver after 6 weeks of treatment and in plasma at 8 weeks of treatment.","[{'text': 'carbamazepine', 'type': 'Chemical', 'start': 8, 'end': 21, 'mesh': 'D002220'}, {'text': 'toxicity', 'type': 'Disease', 'start': 54, 'end': 62, 'mesh': 'D064420'}, {'text': 'folate', 'type': 'Chemical', 'start': 96, 'end': 102, 'mesh': 'D005492'}, {'text': 'Folate', 'type': 'Chemical', 'start': 119, 'end': 125, 'mesh': 'D005492'}, {'text': 'Carbamazepine', 'type': 'Chemical', 'start': 206, 'end': 219, 'mesh': 'D002220'}, {'text': 'CBZ', 'type': 'Chemical', 'start': 221, 'end': 224, 'mesh': 'D002220'}, {'text': 'CBZ', 'type': 'Chemical', 'start': 354, 'end': 357, 'mesh': 'D002220'}, {'text': 'folate', 'type': 'Chemical', 'start': 371, 'end': 377, 'mesh': 'D005492'}, {'text': 'propylene glycol', 'type': 'Chemical', 'start': 463, 'end': 479, 'mesh': 'D019946'}, {'text': 'seizures', 'type': 'Disease', 'start': 565, 'end': 573, 'mesh': 'D012640'}, {'text': 'weight gain', 'type': 'Disease', 'start': 588, 'end': 599, 'mesh': 'D015430'}, {'text': 'Seizures', 'type': 'Disease', 'start': 601, 'end': 609, 'mesh': 'D012640'}, {'text': 'hexafluorodiethyl ether', 'type': 'Chemical', 'start': 621, 'end': 644, 'mesh': 'D005481'}, {'text': 'HFDE', 'type': 'Chemical', 'start': 646, 'end': 650, 'mesh': 'D005481'}, {'text': 'CBZ', 'type': 'Chemical', 'start': 716, 'end': 719, 'mesh': 'D002220'}, {'text': 'seizures', 'type': 'Disease', 'start': 725, 'end': 733, 'mesh': 'D012640'}, {'text': 'CBZ', 'type': 'Chemical', 'start': 796, 'end': 799, 'mesh': 'D002220'}, {'text': 'HFDE', 'type': 'Chemical', 'start': 894, 'end': 898, 'mesh': 'D005481'}, {'text': 'seizures', 'type': 'Disease', 'start': 907, 'end': 915, 'mesh': 'D012640'}, {'text': 'weight gain', 'type': 'Disease', 'start': 955, 'end': 966, 'mesh': 'D015430'}, {'text': 'CBZ', 'type': 'Chemical', 'start': 998, 'end': 1001, 'mesh': 'D002220'}, {'text': 'CBZ', 'type': 'Chemical', 'start': 1134, 'end': 1137, 'mesh': 'D002220'}, {'text': 'folate', 'type': 'Chemical', 'start': 1172, 'end': 1178, 'mesh': 'D005492'}, {'text': 'folate', 'type': 'Chemical', 'start': 1223, 'end': 1229, 'mesh': 'D005492'}]"
+17,2951327,Inhibition of sympathoadrenal activity by atrial natriuretic factor in dogs.,"In six conscious, trained dogs, maintained on a normal sodium intake of 2 to 4 mEq/kg/day, sympathetic activity was assessed as the release rate of norepinephrine and epinephrine during 15-minute i.v. infusions of human alpha-atrial natriuretic factor. Mean arterial pressure (as a percentage of control +/- SEM) during randomized infusions of 0.03, 0.1, 0.3, or 1.0 microgram/kg/min was 99 +/- 1, 95 +/- 1 (p less than 0.05), 93 +/- 1 (p less than 0.01), or 79 +/- 6% (p less than 0.001), respectively, but no tachycardia and no augmentation of the norepinephrine release rate (up to 0.3 microgram/kg/min) were observed, which is in contrast to comparable hypotension induced by hydralazine or nitroglycerin. The release rate of epinephrine (control, 6.7 +/- 0.6 ng/kg/min) declined immediately during infusions of atrial natriuretic factor to a minimum of 49 +/- 5% of control (p less than 0.001) during 0.1 microgram/kg/min and to 63 +/- 5% (0.1 greater than p greater than 0.05) or 95 +/- 13% (not significant) during 0.3 or 1.0 microgram/kg/min. Steady state arterial plasma concentrations of atrial natriuretic factor were 39 +/- 10 pg/ml (n = 6) during infusions of saline and 284 +/- 24 pg/ml (n = 6) and 1520 +/- 300 pg/ml (n = 9) during 0.03 and 0.1 microgram/kg/min infusions of the factor.(ABSTRACT TRUNCATED AT 250 WORDS)","[{'text': 'sodium', 'type': 'Chemical', 'start': 132, 'end': 138, 'mesh': 'D012964'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 225, 'end': 239, 'mesh': 'D009638'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 244, 'end': 255, 'mesh': 'D004837'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 588, 'end': 599, 'mesh': 'D013610'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 627, 'end': 641, 'mesh': 'D009638'}, {'text': 'hypotension', 'type': 'Disease', 'start': 734, 'end': 745, 'mesh': 'D007022'}, {'text': 'hydralazine', 'type': 'Chemical', 'start': 757, 'end': 768, 'mesh': 'D006830'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 772, 'end': 785, 'mesh': 'D005996'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 807, 'end': 818, 'mesh': 'D004837'}]"
+18,3192036,Death from chemotherapy in gestational trophoblastic disease.,"Multiple cytotoxic drug administration is the generally accepted treatment of patients with a high-risk stage of choriocarcinoma. Based on this principle a 27-year old woman, classified as being in the high-risk group (Goldstein and Berkowitz score: 11), was treated with multiple cytotoxic drugs. The multiple drug schema consisted of: Etoposide 16.213, Methotrexate, Cyclophosphamide, Actomycin-D, and Cisplatin. On the first day of the schedule, moderate high doses of Methotrexate, Etoposide and Cyclophosphamide were administered. Within 8 hours after initiation of therapy the patient died with a clinical picture resembling massive pulmonary obstruction due to choriocarcinomic tissue plugs, probably originating from the uterus. Formation of these plugs was probably due to extensive tumor necrosis at the level of the walls of the major uterine veins, which resulted in an open exchange of tumor plugs to the vascular spaces; decrease in tumor tissue coherence secondary to chemotherapy may have further contributed to the formation of tumor emboli. In view of the close time association between the start of chemotherapy and the acute onset of massive embolism other explanations, such as spontaneous necrosis, must be considered less likely. Patients with large pelvic tumor loads are, according to existing classifications, at high risk to die and to develop drug resistance. Notwithstanding these facts our findings suggest that these patients might benefit from relatively mild initial treatment, especially true for patients not previously exposed to this drug. Close observation of the response status both clinically and with beta-hCG values may indicate whether and when more agressive combination chemotherapy should be started.(ABSTRACT TRUNCATED AT 250 WORDS)","[{'text': 'Death', 'type': 'Disease', 'start': 0, 'end': 5, 'mesh': 'D003643'}, {'text': 'gestational trophoblastic disease', 'type': 'Disease', 'start': 27, 'end': 60, 'mesh': 'D031901'}, {'text': 'choriocarcinoma', 'type': 'Disease', 'start': 175, 'end': 190, 'mesh': 'D002822'}, {'text': 'Etoposide', 'type': 'Chemical', 'start': 399, 'end': 408, 'mesh': 'D005047'}, {'text': 'Methotrexate', 'type': 'Chemical', 'start': 417, 'end': 429, 'mesh': 'D008727'}, {'text': 'Cyclophosphamide', 'type': 'Chemical', 'start': 431, 'end': 447, 'mesh': 'D003520'}, {'text': 'Actomycin-D', 'type': 'Chemical', 'start': 449, 'end': 460, 'mesh': 'D003609'}, {'text': 'Cisplatin', 'type': 'Chemical', 'start': 466, 'end': 475, 'mesh': 'D002945'}, {'text': 'Methotrexate', 'type': 'Chemical', 'start': 534, 'end': 546, 'mesh': 'D008727'}, {'text': 'Etoposide', 'type': 'Chemical', 'start': 548, 'end': 557, 'mesh': 'D005047'}, {'text': 'Cyclophosphamide', 'type': 'Chemical', 'start': 562, 'end': 578, 'mesh': 'D003520'}, {'text': 'pulmonary obstruction', 'type': 'Disease', 'start': 701, 'end': 722, 'mesh': 'D011655'}, {'text': 'tumor', 'type': 'Disease', 'start': 854, 'end': 859, 'mesh': 'D009369'}, {'text': 'necrosis', 'type': 'Disease', 'start': 860, 'end': 868, 'mesh': 'D009336'}, {'text': 'tumor', 'type': 'Disease', 'start': 961, 'end': 966, 'mesh': 'D009369'}, {'text': 'tumor', 'type': 'Disease', 'start': 1009, 'end': 1014, 'mesh': 'D009369'}, {'text': 'tumor', 'type': 'Disease', 'start': 1107, 'end': 1112, 'mesh': 'D009369'}, {'text': 'embolism', 'type': 'Disease', 'start': 1224, 'end': 1232, 'mesh': 'D004617'}, {'text': 'necrosis', 'type': 'Disease', 'start': 1273, 'end': 1281, 'mesh': 'D009336'}, {'text': 'pelvic tumor', 'type': 'Disease', 'start': 1335, 'end': 1347, 'mesh': 'D010386'}]"
+19,3409645,Sexual dysfunction among patients with arthritis.,"The relationship of arthritis and sexual dysfunction was investigated among 169 patients with rheumatoid arthritis, osteoarthritis and spondyloarthropathy, 130 of whom were pair-matched to controls. Assessments of marital happiness and depressed mood were also made using the CES-D and the Azrin Marital Happiness Scale (AMHS). Sexual dysfunctions were found to be common among patients and controls, the majority in both groups reporting one or more dysfunctions. Impotence was more common among male patients than controls and was found to be associated with co-morbidity and the taking of methotrexate. Depressed mood was more common among patients and was associated with certain sexual difficulties, but not with impotence. Marital unhappiness, as indicated by AMHS scores, was not associated with arthritis but was associated with sexual dysfunction, sexual dissatisfaction and being female.","[{'text': 'Sexual dysfunction', 'type': 'Disease', 'start': 0, 'end': 18, 'mesh': 'D012735'}, {'text': 'arthritis', 'type': 'Disease', 'start': 39, 'end': 48, 'mesh': 'D001168'}, {'text': 'arthritis', 'type': 'Disease', 'start': 70, 'end': 79, 'mesh': 'D001168'}, {'text': 'sexual dysfunction', 'type': 'Disease', 'start': 84, 'end': 102, 'mesh': 'D012735'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 144, 'end': 164, 'mesh': 'D001172'}, {'text': 'osteoarthritis', 'type': 'Disease', 'start': 166, 'end': 180, 'mesh': 'D010003'}, {'text': 'spondyloarthropathy', 'type': 'Disease', 'start': 185, 'end': 204, 'mesh': 'D025242'}, {'text': 'depressed mood', 'type': 'Disease', 'start': 286, 'end': 300, 'mesh': 'D003866'}, {'text': 'Sexual dysfunctions', 'type': 'Disease', 'start': 378, 'end': 397, 'mesh': 'D012735'}, {'text': 'Impotence', 'type': 'Disease', 'start': 515, 'end': 524, 'mesh': 'D007172'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 642, 'end': 654, 'mesh': 'D008727'}, {'text': 'Depressed mood', 'type': 'Disease', 'start': 656, 'end': 670, 'mesh': 'D003866'}, {'text': 'impotence', 'type': 'Disease', 'start': 768, 'end': 777, 'mesh': 'D007172'}, {'text': 'arthritis', 'type': 'Disease', 'start': 853, 'end': 862, 'mesh': 'D001168'}, {'text': 'sexual dysfunction', 'type': 'Disease', 'start': 887, 'end': 905, 'mesh': 'D012735'}]"
+20,3412544,Does paracetamol cause urothelial cancer or renal papillary necrosis?,"The risk of developing renal papillary necrosis or cancer of the renal pelvis, ureter or bladder associated with consumption of either phenacetin or paracetamol was calculated from data acquired by questionnaire from 381 cases and 808 controls. The risk of renal papillary necrosis was increased nearly 20-fold by consumption of phenacetin, which also increased the risk for cancer of the renal pelvis and bladder but not for ureteric cancer. By contrast, we were unable to substantiate an increased risk from paracetamol consumption for renal papillary necrosis or any of these cancers although there was a suggestion of an association with cancer of the ureter.","[{'text': 'paracetamol', 'type': 'Chemical', 'start': 5, 'end': 16, 'mesh': 'D000082'}, {'text': 'urothelial cancer', 'type': 'Disease', 'start': 23, 'end': 40, 'mesh': 'D014523'}, {'text': 'renal papillary necrosis', 'type': 'Disease', 'start': 44, 'end': 68, 'mesh': 'D007681'}, {'text': 'renal papillary necrosis', 'type': 'Disease', 'start': 93, 'end': 117, 'mesh': 'D007681'}, {'text': 'phenacetin', 'type': 'Chemical', 'start': 205, 'end': 215, 'mesh': 'D010615'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 219, 'end': 230, 'mesh': 'D000082'}, {'text': 'renal papillary necrosis', 'type': 'Disease', 'start': 327, 'end': 351, 'mesh': 'D007681'}, {'text': 'phenacetin', 'type': 'Chemical', 'start': 399, 'end': 409, 'mesh': 'D010615'}, {'text': 'ureteric cancer', 'type': 'Disease', 'start': 496, 'end': 511, 'mesh': 'D014516'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 580, 'end': 591, 'mesh': 'D000082'}, {'text': 'renal papillary necrosis', 'type': 'Disease', 'start': 608, 'end': 632, 'mesh': 'D007681'}, {'text': 'cancers', 'type': 'Disease', 'start': 649, 'end': 656, 'mesh': 'D009369'}, {'text': 'cancer of the ureter', 'type': 'Disease', 'start': 712, 'end': 732, 'mesh': 'D014516'}]"
+21,3425586,Dapsone-associated Heinz body hemolytic anemia in a Cambodian woman with hemoglobin E trait.,"A Cambodian woman with hemoglobin E trait (AE) and leprosy developed a Heinz body hemolytic anemia while taking a dose of dapsone (50 mg/day) not usually associated with clinical hemolysis. Her red blood cells (RBCs) had increased incubated Heinz body formation, decreased reduced glutathione (GSH), and decreased GSH stability. The pentose phosphate shunt activity of the dapsone-exposed AE RBCs was increased compared to normal RBCs. Although the AE RBCs from an individual not taking dapsone had increased incubated Heinz body formation, the GSH content and GSH stability were normal. The pentose phosphate shunt activity of the non-dapsone-exposed AE RBCs was decreased compared to normal RBCs. Thus, AE RBCs appear to have an increased sensitivity to oxidant stress both in vitro and in vivo, since dapsone does not cause hemolytic anemia at this dose in hematologically normal individuals. Given the influx of Southeast Asians into the United States, oxidant medications should be used with caution, especially if an infection is present, in individuals of ethnic backgrounds that have an increased prevalence of hemoglobin E.","[{'text': 'Dapsone', 'type': 'Chemical', 'start': 0, 'end': 7, 'mesh': 'D003622'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 30, 'end': 46, 'mesh': 'D000743'}, {'text': 'leprosy', 'type': 'Disease', 'start': 144, 'end': 151, 'mesh': 'D007918'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 175, 'end': 191, 'mesh': 'D000743'}, {'text': 'dapsone', 'type': 'Chemical', 'start': 215, 'end': 222, 'mesh': 'D003622'}, {'text': 'hemolysis', 'type': 'Disease', 'start': 272, 'end': 281, 'mesh': 'D006461'}, {'text': 'glutathione', 'type': 'Chemical', 'start': 374, 'end': 385, 'mesh': 'D005978'}, {'text': 'GSH', 'type': 'Chemical', 'start': 387, 'end': 390, 'mesh': 'D005978'}, {'text': 'GSH', 'type': 'Chemical', 'start': 407, 'end': 410, 'mesh': 'D005978'}, {'text': 'pentose phosphate', 'type': 'Chemical', 'start': 426, 'end': 443, 'mesh': 'D010428'}, {'text': 'dapsone', 'type': 'Chemical', 'start': 466, 'end': 473, 'mesh': 'D003622'}, {'text': 'dapsone', 'type': 'Chemical', 'start': 580, 'end': 587, 'mesh': 'D003622'}, {'text': 'GSH', 'type': 'Chemical', 'start': 638, 'end': 641, 'mesh': 'D005978'}, {'text': 'GSH', 'type': 'Chemical', 'start': 654, 'end': 657, 'mesh': 'D005978'}, {'text': 'pentose phosphate', 'type': 'Chemical', 'start': 685, 'end': 702, 'mesh': 'D010428'}, {'text': 'dapsone', 'type': 'Chemical', 'start': 729, 'end': 736, 'mesh': 'D003622'}, {'text': 'dapsone', 'type': 'Chemical', 'start': 897, 'end': 904, 'mesh': 'D003622'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 920, 'end': 936, 'mesh': 'D000743'}, {'text': 'infection', 'type': 'Disease', 'start': 1116, 'end': 1125, 'mesh': 'D007239'}]"
+22,3437726,"Severe complications of antianginal drug therapy in a patient identified as a poor metabolizer of metoprolol, propafenone, diltiazem, and sparteine.","A 47-year-old patient suffering from coronary artery disease was admitted to the CCU in shock with III. AV block, severe hypotension, and impairment of ventricular function. One week prior to admission a therapy with standard doses of metoprolol (100 mg t.i.d. and then 100 mg b.i.d.) had been initiated. Two days before admission diltiazem (60 mg b.i.d.) was prescribed in addition. Analyses of a blood sample revealed unusually high plasma concentrations of metoprolol (greater than 3000 ng/ml) and diltiazem (526 ng/ml). The patient recovered within 1 week following discontinuation of antianginal therapy. Three months later the patient was exposed to a single dose of metoprolol, diltiazem, propafenone (since he had received this drug in the past), and sparteine (as a probe for the debrisoquine/sparteine type polymorphism of oxidative drug metabolism). It was found that he was a poor metabolizer of all four drugs, indicating that their metabolism is under the same genetic control. Therefore, patients belonging to the poor-metabolizer phenotype of sparteine/debrisoquine polymorphism in drug metabolism, which constitutes 6.4% of the German population, may experience adverse drug reactions when treated with standard doses of one of these drugs alone. Moreover, the coadministration of these frequently used drugs is expected to be especially harmful in this subgroup of patients.","[{'text': 'metoprolol', 'type': 'Chemical', 'start': 98, 'end': 108, 'mesh': 'D008790'}, {'text': 'propafenone', 'type': 'Chemical', 'start': 110, 'end': 121, 'mesh': 'D011405'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 123, 'end': 132, 'mesh': 'D004110'}, {'text': 'sparteine', 'type': 'Chemical', 'start': 138, 'end': 147, 'mesh': 'D013034'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 186, 'end': 209, 'mesh': 'D003324'}, {'text': 'shock', 'type': 'Disease', 'start': 237, 'end': 242, 'mesh': 'D012769'}, {'text': 'AV block', 'type': 'Disease', 'start': 253, 'end': 261, 'mesh': 'D054537'}, {'text': 'hypotension', 'type': 'Disease', 'start': 270, 'end': 281, 'mesh': 'D007022'}, {'text': 'impairment of ventricular function', 'type': 'Disease', 'start': 287, 'end': 321, 'mesh': 'D018754'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 384, 'end': 394, 'mesh': 'D008790'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 480, 'end': 489, 'mesh': 'D004110'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 609, 'end': 619, 'mesh': 'D008790'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 650, 'end': 659, 'mesh': 'D004110'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 822, 'end': 832, 'mesh': 'D008790'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 834, 'end': 843, 'mesh': 'D004110'}, {'text': 'propafenone', 'type': 'Chemical', 'start': 845, 'end': 856, 'mesh': 'D011405'}, {'text': 'sparteine', 'type': 'Chemical', 'start': 908, 'end': 917, 'mesh': 'D013034'}, {'text': 'debrisoquine', 'type': 'Chemical', 'start': 938, 'end': 950, 'mesh': 'D003647'}, {'text': 'sparteine', 'type': 'Chemical', 'start': 951, 'end': 960, 'mesh': 'D013034'}, {'text': 'sparteine', 'type': 'Chemical', 'start': 1208, 'end': 1217, 'mesh': 'D013034'}, {'text': 'debrisoquine', 'type': 'Chemical', 'start': 1218, 'end': 1230, 'mesh': 'D003647'}, {'text': 'adverse drug reactions', 'type': 'Disease', 'start': 1328, 'end': 1350, 'mesh': 'D064420'}]"
+23,3693336,Triazolam-induced brief episodes of secondary mania in a depressed patient.,Large doses of triazolam repeatedly induced brief episodes of mania in a depressed elderly woman. Features of organic mental disorder (delirium) were not present. Manic excitement was coincident with the duration of action of triazolam. The possible contribution of the triazolo group to changes in affective status is discussed.,"[{'text': 'Triazolam', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D014229'}, {'text': 'mania', 'type': 'Disease', 'start': 46, 'end': 51, 'mesh': 'D001714'}, {'text': 'depressed', 'type': 'Disease', 'start': 57, 'end': 66, 'mesh': 'D003866'}, {'text': 'triazolam', 'type': 'Chemical', 'start': 91, 'end': 100, 'mesh': 'D014229'}, {'text': 'mania', 'type': 'Disease', 'start': 138, 'end': 143, 'mesh': 'D001714'}, {'text': 'depressed', 'type': 'Disease', 'start': 149, 'end': 158, 'mesh': 'D003866'}, {'text': 'organic mental disorder', 'type': 'Disease', 'start': 186, 'end': 209, 'mesh': 'D019965'}, {'text': 'delirium', 'type': 'Disease', 'start': 211, 'end': 219, 'mesh': 'D003693'}, {'text': 'Manic', 'type': 'Disease', 'start': 239, 'end': 244, 'mesh': 'D001714'}, {'text': 'triazolam', 'type': 'Chemical', 'start': 302, 'end': 311, 'mesh': 'D014229'}, {'text': 'triazolo', 'type': 'Chemical', 'start': 346, 'end': 354, 'mesh': 'D014229'}]"
+24,3780846,On the mechanisms of the development of tolerance to the muscular rigidity produced by morphine in rats.,"The development of tolerance to the muscular rigidity produced by morphine was studied in rats. Saline-pretreated controls given a test dose of morphine (20 mg/kg i.p.) showed a pronounced rigidity recorded as tonic activity in the electromyogram. Rats treated for 11 days with morphine and withdrawn for 36-40 h showed differences in the development of tolerance: about half of the animals showed a rigidity after the test dose of morphine that was not significantly less than in the controls and were akinetic (A group). The other rats showed a strong decrease in the rigidity and the occurrence of stereotyped (S) licking and/or gnawing in presence of akinetic or hyperkinetic (K) behaviour (AS/KS group), suggesting signs of dopaminergic activation. The rigidity was considerably decreased in both groups after 20 days' treatment. In a further series of experiments, haloperidol (0.2 mg/kg i.p.) was used in order to block the dopaminergic activation and to estimate the real degree of the tolerance to the rigidity without any dopaminergic interference. Haloperidol enhanced the rigidity in the A group. However, the level in the AS/KS group remained considerably lower than in the A group. The results suggest that rigidity, which is assumed to be due to an action of morphine in the striatum, can be antagonized by another process leading to dopaminergic activation in the striatum. Nevertheless, there occurs some real tolerance to this effect. The rapid alternations of rigidity and the signs of dopaminergic activation observed in the animals of the AS/KS group might be due to rapid shifts in the predominance of various DA-innervated structures.","[{'text': 'muscular rigidity', 'type': 'Disease', 'start': 57, 'end': 74, 'mesh': 'D009127'}, {'text': 'morphine', 'type': 'Chemical', 'start': 87, 'end': 95, 'mesh': 'D009020'}, {'text': 'muscular rigidity', 'type': 'Disease', 'start': 141, 'end': 158, 'mesh': 'D009127'}, {'text': 'morphine', 'type': 'Chemical', 'start': 171, 'end': 179, 'mesh': 'D009020'}, {'text': 'morphine', 'type': 'Chemical', 'start': 249, 'end': 257, 'mesh': 'D009020'}, {'text': 'rigidity', 'type': 'Disease', 'start': 294, 'end': 302, 'mesh': 'D009127'}, {'text': 'morphine', 'type': 'Chemical', 'start': 383, 'end': 391, 'mesh': 'D009020'}, {'text': 'rigidity', 'type': 'Disease', 'start': 505, 'end': 513, 'mesh': 'D009127'}, {'text': 'morphine', 'type': 'Chemical', 'start': 537, 'end': 545, 'mesh': 'D009020'}, {'text': 'akinetic', 'type': 'Disease', 'start': 608, 'end': 616, 'mesh': 'D018476'}, {'text': 'rigidity', 'type': 'Disease', 'start': 675, 'end': 683, 'mesh': 'D009127'}, {'text': 'akinetic', 'type': 'Disease', 'start': 760, 'end': 768, 'mesh': 'D018476'}, {'text': 'hyperkinetic', 'type': 'Disease', 'start': 772, 'end': 784, 'mesh': 'D006948'}, {'text': 'rigidity', 'type': 'Disease', 'start': 863, 'end': 871, 'mesh': 'D009127'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 976, 'end': 987, 'mesh': 'D006220'}, {'text': 'rigidity', 'type': 'Disease', 'start': 1116, 'end': 1124, 'mesh': 'D009127'}, {'text': 'Haloperidol', 'type': 'Chemical', 'start': 1164, 'end': 1175, 'mesh': 'D006220'}, {'text': 'rigidity', 'type': 'Disease', 'start': 1189, 'end': 1197, 'mesh': 'D009127'}, {'text': 'rigidity', 'type': 'Disease', 'start': 1326, 'end': 1334, 'mesh': 'D009127'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1379, 'end': 1387, 'mesh': 'D009020'}, {'text': 'rigidity', 'type': 'Disease', 'start': 1584, 'end': 1592, 'mesh': 'D009127'}]"
+25,3800626,Compression neuropathy of the radial nerve due to pentazocine-induced fibrous myopathy.,"Fibrous myopathy is a common, well-known side effect of repeated pentazocine injection. However, compression neuropathy due to fibrotic muscle affected by pentazocine-induced myopathy has not previously been reported. In a 37-year-old woman with documented pentazocine-induced fibrous myopathy of triceps and deltoid muscles bilaterally and a three-week history of right wrist drop, electrodiagnostic examination showed a severe but partial lesion of the right radial nerve distal to the branches to the triceps, in addition to the fibrous myopathy. Surgery revealed the right radial nerve to be severely compressed by the densely fibrotic lateral head of the triceps. Decompression and neurolysis were performed with good subsequent recovery of function.","[{'text': 'pentazocine', 'type': 'Chemical', 'start': 50, 'end': 61, 'mesh': 'D010423'}, {'text': 'fibrous myopathy', 'type': 'Disease', 'start': 70, 'end': 86, 'mesh': 'D005355|D009135'}, {'text': 'Fibrous myopathy', 'type': 'Disease', 'start': 88, 'end': 104, 'mesh': 'D005355|D009135'}, {'text': 'pentazocine', 'type': 'Chemical', 'start': 153, 'end': 164, 'mesh': 'D010423'}, {'text': 'compression neuropathy', 'type': 'Disease', 'start': 185, 'end': 207, 'mesh': 'D009408'}, {'text': 'pentazocine', 'type': 'Chemical', 'start': 243, 'end': 254, 'mesh': 'D010423'}, {'text': 'myopathy', 'type': 'Disease', 'start': 263, 'end': 271, 'mesh': 'D009135'}, {'text': 'pentazocine', 'type': 'Chemical', 'start': 345, 'end': 356, 'mesh': 'D010423'}, {'text': 'fibrous myopathy', 'type': 'Disease', 'start': 365, 'end': 381, 'mesh': 'D005355|D009135'}, {'text': 'fibrous myopathy', 'type': 'Disease', 'start': 620, 'end': 636, 'mesh': 'D005355|D009135'}]"
+26,3827439,Recurrent reversible acute renal failure from amphotericin.,"A patient with cryptogenic cirrhosis and disseminated sporotrichosis developed acute renal failure immediately following the administration of amphotericin B on four separate occasions. The abruptness of the renal failure and its reversibility within days suggests that there was a functional component to the renal dysfunction. We propose that amphotericin, in the setting of reduced effective arterial volume, may activate tubuloglomerular feedback, thereby contributing to acute renal failure.","[{'text': 'acute renal failure', 'type': 'Disease', 'start': 21, 'end': 40, 'mesh': 'D058186'}, {'text': 'amphotericin', 'type': 'Chemical', 'start': 46, 'end': 58, 'mesh': 'D000666'}, {'text': 'cirrhosis', 'type': 'Disease', 'start': 87, 'end': 96, 'mesh': 'D005355'}, {'text': 'sporotrichosis', 'type': 'Disease', 'start': 114, 'end': 128, 'mesh': 'D013174'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 139, 'end': 158, 'mesh': 'D058186'}, {'text': 'amphotericin B', 'type': 'Chemical', 'start': 203, 'end': 217, 'mesh': 'D000666'}, {'text': 'renal failure', 'type': 'Disease', 'start': 268, 'end': 281, 'mesh': 'D051437'}, {'text': 'renal dysfunction', 'type': 'Disease', 'start': 370, 'end': 387, 'mesh': 'D007674'}, {'text': 'amphotericin', 'type': 'Chemical', 'start': 405, 'end': 417, 'mesh': 'D000666'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 536, 'end': 555, 'mesh': 'D058186'}]"
+27,3997294,Pneumonitis with pleural and pericardial effusion and neuropathy during amiodarone therapy.,"A patient with sinuatrial disease and implanted pacemaker was treated with amiodarone (maximum dose 1000 mg, maintenance dose 800 mg daily) for 10 months, for control of supraventricular tachyarrhythmias. He developed pneumonitis, pleural and pericardial effusions, and a predominantly proximal motor neuropathy. Immediate but gradual improvement followed withdrawal of amiodarone and treatment with prednisolone. Review of this and previously reported cases indicates the need for early diagnosis of amiodarone pneumonitis, immediate withdrawal of amiodarone, and prompt but continued steroid therapy to ensure full recovery.","[{'text': 'neuropathy', 'type': 'Disease', 'start': 54, 'end': 64, 'mesh': 'D009422'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 72, 'end': 82, 'mesh': 'D000638'}, {'text': 'sinuatrial disease', 'type': 'Disease', 'start': 107, 'end': 125, 'mesh': 'D002318'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 167, 'end': 177, 'mesh': 'D000638'}, {'text': 'supraventricular tachyarrhythmias', 'type': 'Disease', 'start': 262, 'end': 295, 'mesh': 'D013617'}, {'text': 'pneumonitis', 'type': 'Disease', 'start': 310, 'end': 321, 'mesh': 'D011014'}, {'text': 'proximal motor neuropathy', 'type': 'Disease', 'start': 378, 'end': 403, 'mesh': 'D009468'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 462, 'end': 472, 'mesh': 'D000638'}, {'text': 'prednisolone', 'type': 'Chemical', 'start': 492, 'end': 504, 'mesh': 'D011239'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 593, 'end': 603, 'mesh': 'D000638'}, {'text': 'pneumonitis', 'type': 'Disease', 'start': 604, 'end': 615, 'mesh': 'D011014'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 641, 'end': 651, 'mesh': 'D000638'}, {'text': 'steroid', 'type': 'Chemical', 'start': 678, 'end': 685, 'mesh': 'D013256'}]"
+28,4071154,Indomethacin-induced renal insufficiency: recurrence on rechallenge.,"We have reported a case of acute oliguric renal failure with hyperkalemia in a patient with cirrhosis, ascites, and cor pulmonale after indomethacin therapy. Prompt restoration of renal function followed drug withdrawal, while re-exposure to a single dose of indomethacin caused recurrence of acute reversible oliguria. Our case supports the hypothesis that endogenous renal prostaglandins play a role in the maintenance of renal blood flow when circulating plasma volume is diminished. Since nonsteroidal anti-inflammatory agents interfere with this compensatory mechanism and may cause acute renal failure, they should be used with caution in such patients.","[{'text': 'Indomethacin', 'type': 'Chemical', 'start': 0, 'end': 12, 'mesh': 'D007213'}, {'text': 'renal insufficiency', 'type': 'Disease', 'start': 21, 'end': 40, 'mesh': 'D051437'}, {'text': 'renal failure', 'type': 'Disease', 'start': 111, 'end': 124, 'mesh': 'D051437'}, {'text': 'hyperkalemia', 'type': 'Disease', 'start': 130, 'end': 142, 'mesh': 'D006947'}, {'text': 'cirrhosis', 'type': 'Disease', 'start': 161, 'end': 170, 'mesh': 'D005355'}, {'text': 'ascites', 'type': 'Disease', 'start': 172, 'end': 179, 'mesh': 'D001201'}, {'text': 'cor pulmonale', 'type': 'Disease', 'start': 185, 'end': 198, 'mesh': 'D011660'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 205, 'end': 217, 'mesh': 'D007213'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 328, 'end': 340, 'mesh': 'D007213'}, {'text': 'oliguria', 'type': 'Disease', 'start': 379, 'end': 387, 'mesh': 'D009846'}, {'text': 'prostaglandins', 'type': 'Chemical', 'start': 444, 'end': 458, 'mesh': 'D011453'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 657, 'end': 676, 'mesh': 'D058186'}]"
+29,6103707,Comparison of the subjective effects and plasma concentrations following oral and i.m. administration of flunitrazepam in volunteers.,"Flunitrazepam 0.5, 1.0 or 2.0 mg was given by the oral or i.m. routes to groups of volunteers and its effects compared. Plasma concentrations of the drug were estimated by gas-liquid chromatography, in a smaller number of the subjects. The most striking effect was sedation which increased with the dose, 2 mg producing deep sleep although the subjects could still be aroused. The effects of i.m. administration were apparent earlier and sometimes lasted longer than those following oral administration. Dizziness was less marked than sedation, but increased with the dose. There was pain on i.m. injection of flunitrazepam significantly more often than with isotonic saline. Plasma concentrations varied with dose and route and corresponded qualitatively with the subjective effects. The drug was still present in measurable quantities after 24 h even with the smallest dose.","[{'text': 'flunitrazepam', 'type': 'Chemical', 'start': 105, 'end': 118, 'mesh': 'D005445'}, {'text': 'Flunitrazepam', 'type': 'Chemical', 'start': 134, 'end': 147, 'mesh': 'D005445'}, {'text': 'Dizziness', 'type': 'Disease', 'start': 638, 'end': 647, 'mesh': 'D004244'}, {'text': 'pain', 'type': 'Disease', 'start': 718, 'end': 722, 'mesh': 'D010146'}, {'text': 'flunitrazepam', 'type': 'Chemical', 'start': 744, 'end': 757, 'mesh': 'D005445'}]"
+30,6229975,Changes in heart size during long-term timolol treatment after myocardial infarction.,"The effect of long-term timolol treatment on heart size after myocardial infarction was evaluated by X-ray in a double-blind study including 241 patients (placebo 126, timolol 115). The follow-up period was 12 months. The timolol-treated patients showed a small but significant increase in heart size from baseline in contrast to a decrease in the placebo group. These differences may be caused by timolol-induced bradycardia and a compensatory increase in end-diastolic volume. The timolol-related increase in heart size was observed only in patients with normal and borderline heart size. In patients with cardiomegaly, the increase in heart size was similar in both groups. After re-infarction, heart size increased in the placebo group and remained unchanged in the timolol group.","[{'text': 'timolol', 'type': 'Chemical', 'start': 39, 'end': 46, 'mesh': 'D013999'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 63, 'end': 84, 'mesh': 'D009203'}, {'text': 'timolol', 'type': 'Chemical', 'start': 110, 'end': 117, 'mesh': 'D013999'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 148, 'end': 169, 'mesh': 'D009203'}, {'text': 'timolol', 'type': 'Chemical', 'start': 254, 'end': 261, 'mesh': 'D013999'}, {'text': 'timolol', 'type': 'Chemical', 'start': 308, 'end': 315, 'mesh': 'D013999'}, {'text': 'timolol', 'type': 'Chemical', 'start': 484, 'end': 491, 'mesh': 'D013999'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 500, 'end': 511, 'mesh': 'D001919'}, {'text': 'timolol', 'type': 'Chemical', 'start': 569, 'end': 576, 'mesh': 'D013999'}, {'text': 'cardiomegaly', 'type': 'Disease', 'start': 694, 'end': 706, 'mesh': 'D006332'}, {'text': 'infarction', 'type': 'Disease', 'start': 772, 'end': 782, 'mesh': 'D007238'}, {'text': 'timolol', 'type': 'Chemical', 'start': 856, 'end': 863, 'mesh': 'D013999'}]"
+31,6286738,Vitamin D3 toxicity in dairy cows.,"Large parenteral doses of vitamin D3 (15 to 17.5 x 10(6) IU vitamin D3) were associated with prolonged hypercalcemia, hyperphosphatemia, and large increases of vitamin D3 and its metabolites in the blood plasma of nonlactating nonpregnant and pregnant Jersey cows. Calcium concentrations 1 day postpartum were higher in cows treated with vitamin D3 about 32 days prepartum (8.8 mg/100 ml) than in control cows (5.5 mg/100 ml). None of the cows treated with vitamin D3 showed signs of milk fever during the peripartal period; however, 22% of the control cows developed clinical signs of milk fever during this period. Signs of vitamin D3 toxicity were not observed in nonlactating nonpregnant cows; however, pregnant cows commonly developed severe signs of vitamin D3 toxicity and 10 of 17 cows died. There was widespread metastatic calcification in the cows that died. Because of the extreme toxicity of vitamin D3 in pregnant Jersey cows and the low margin of safety between doses of vitamin D3 that prevent milk fever and doses that induce milk fever, we concluded that vitamin D3 cannot be used practically to prevent milk fever when injected several weeks prepartum.","[{'text': 'Vitamin D3', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D002762'}, {'text': 'toxicity', 'type': 'Disease', 'start': 11, 'end': 19, 'mesh': 'D064420'}, {'text': 'vitamin D3', 'type': 'Chemical', 'start': 61, 'end': 71, 'mesh': 'D002762'}, {'text': 'vitamin D3', 'type': 'Chemical', 'start': 95, 'end': 105, 'mesh': 'D002762'}, {'text': 'hypercalcemia', 'type': 'Disease', 'start': 138, 'end': 151, 'mesh': 'D006934'}, {'text': 'hyperphosphatemia', 'type': 'Disease', 'start': 153, 'end': 170, 'mesh': 'D054559'}, {'text': 'vitamin D3', 'type': 'Chemical', 'start': 195, 'end': 205, 'mesh': 'D002762'}, {'text': 'Calcium', 'type': 'Chemical', 'start': 300, 'end': 307, 'mesh': 'D002118'}, {'text': 'vitamin D3', 'type': 'Chemical', 'start': 373, 'end': 383, 'mesh': 'D002762'}, {'text': 'vitamin D3', 'type': 'Chemical', 'start': 492, 'end': 502, 'mesh': 'D002762'}, {'text': 'milk fever', 'type': 'Disease', 'start': 519, 'end': 529, 'mesh': 'D010319'}, {'text': 'milk fever', 'type': 'Disease', 'start': 621, 'end': 631, 'mesh': 'D010319'}, {'text': 'vitamin D3', 'type': 'Chemical', 'start': 661, 'end': 671, 'mesh': 'D002762'}, {'text': 'toxicity', 'type': 'Disease', 'start': 672, 'end': 680, 'mesh': 'D064420'}, {'text': 'vitamin D3', 'type': 'Chemical', 'start': 791, 'end': 801, 'mesh': 'D002762'}, {'text': 'toxicity', 'type': 'Disease', 'start': 802, 'end': 810, 'mesh': 'D064420'}, {'text': 'toxicity', 'type': 'Disease', 'start': 927, 'end': 935, 'mesh': 'D064420'}, {'text': 'vitamin D3', 'type': 'Chemical', 'start': 939, 'end': 949, 'mesh': 'D002762'}, {'text': 'vitamin D3', 'type': 'Chemical', 'start': 1020, 'end': 1030, 'mesh': 'D002762'}, {'text': 'milk fever', 'type': 'Disease', 'start': 1044, 'end': 1054, 'mesh': 'D010319'}, {'text': 'milk fever', 'type': 'Disease', 'start': 1077, 'end': 1087, 'mesh': 'D010319'}, {'text': 'vitamin D3', 'type': 'Chemical', 'start': 1107, 'end': 1117, 'mesh': 'D002762'}, {'text': 'milk fever', 'type': 'Disease', 'start': 1156, 'end': 1166, 'mesh': 'D010319'}]"
+32,6287825,Diseases of peripheral nerves as seen in the Nigerian African.,"The anatomical and aetiological diagnoses of peripheral nerve disease excluding its primary benign and malignant disorders, as seen in 358 Nigerians are presented. There is a male preponderance and the peak incidence is in the fourth decade. Sensori-motor neuropathy was the commonest presentation (50%). Guillain-Barr   syndrome was the commonest identifiable cause (15.6%), accounting for half of the cases with motor neuropathy. Peripheral neuropathy due to nutritional deficiency of thiamine and riboflavin was common (10.1%) and presented mainly as sensory and sensori-motor neuropathy. Diabetes mellitus was the major cause of autonomic neuropathy. Isoniazid was the most frequent agent in drug-induced neuropathy. Migraine (20%) was not an uncommon cause of cranial neuropathy although malignancies arising from the reticuloendothelial system or related structures of the head and neck were more frequent (26%). In 26.5% of all the cases, the aetiology of the neuropathy was undetermined. Heredofamilial and connective tissue disorders were rare. Some of the factors related to the clinical presentation and pathogenesis of the neuropathies are briefly discussed.","[{'text': 'Diseases of peripheral nerves', 'type': 'Disease', 'start': 0, 'end': 29, 'mesh': 'D010523'}, {'text': 'peripheral nerve disease', 'type': 'Disease', 'start': 108, 'end': 132, 'mesh': 'D010523'}, {'text': 'Sensori-motor neuropathy', 'type': 'Disease', 'start': 305, 'end': 329, 'mesh': 'D010523'}, {'text': 'Guillain-Barr   syndrome', 'type': 'Disease', 'start': 368, 'end': 392, 'mesh': 'D020275'}, {'text': 'motor neuropathy', 'type': 'Disease', 'start': 477, 'end': 493, 'mesh': 'D010523'}, {'text': 'Peripheral neuropathy', 'type': 'Disease', 'start': 495, 'end': 516, 'mesh': 'D010523'}, {'text': 'nutritional deficiency', 'type': 'Disease', 'start': 524, 'end': 546, 'mesh': 'D044342'}, {'text': 'thiamine', 'type': 'Chemical', 'start': 550, 'end': 558, 'mesh': 'D013831'}, {'text': 'riboflavin', 'type': 'Chemical', 'start': 563, 'end': 573, 'mesh': 'D012256'}, {'text': 'sensori-motor neuropathy', 'type': 'Disease', 'start': 629, 'end': 653, 'mesh': 'D010523'}, {'text': 'Diabetes mellitus', 'type': 'Disease', 'start': 655, 'end': 672, 'mesh': 'D003920'}, {'text': 'autonomic neuropathy', 'type': 'Disease', 'start': 696, 'end': 716, 'mesh': 'D009422'}, {'text': 'Isoniazid', 'type': 'Chemical', 'start': 718, 'end': 727, 'mesh': 'D007538'}, {'text': 'neuropathy', 'type': 'Disease', 'start': 772, 'end': 782, 'mesh': 'D009422'}, {'text': 'Migraine', 'type': 'Disease', 'start': 784, 'end': 792, 'mesh': 'D008881'}, {'text': 'cranial neuropathy', 'type': 'Disease', 'start': 828, 'end': 846, 'mesh': 'D003389'}, {'text': 'malignancies', 'type': 'Disease', 'start': 856, 'end': 868, 'mesh': 'D009369'}, {'text': 'neuropathy', 'type': 'Disease', 'start': 1030, 'end': 1040, 'mesh': 'D009422'}, {'text': 'connective tissue disorders', 'type': 'Disease', 'start': 1078, 'end': 1105, 'mesh': 'D003240'}, {'text': 'neuropathies', 'type': 'Disease', 'start': 1198, 'end': 1210, 'mesh': 'D009422'}]"
+33,6386793,A double-blind study of the efficacy and safety of dothiepin hydrochloride in the treatment of major depressive disorder.,"In a 6-week double-blind parallel treatment study, dothiepin and amitriptyline were compared to placebo in the treatment of 33 depressed outpatients. Dothiepin and amitriptyline were equally effective in alleviating the symptoms of depressive illness, and both were significantly superior to placebo. The overall incidence of side effects and the frequency and severity of blurred vision, dry mouth, and drowsiness were significantly less with dothiepin than with amitriptyline. Dothiepin also produced fewer CNS and cardiovascular effects. There were no clinically important changes in laboratory parameters. Dothiepin thus was found to be an effective antidepressant drug associated with fewer side effects than amitriptyline in the treatment of depressed outpatients.","[{'text': 'dothiepin hydrochloride', 'type': 'Chemical', 'start': 51, 'end': 74, 'mesh': 'D004308'}, {'text': 'depressive disorder', 'type': 'Disease', 'start': 101, 'end': 120, 'mesh': 'D003866'}, {'text': 'dothiepin', 'type': 'Chemical', 'start': 173, 'end': 182, 'mesh': 'D004308'}, {'text': 'amitriptyline', 'type': 'Chemical', 'start': 187, 'end': 200, 'mesh': 'D000639'}, {'text': 'depressed', 'type': 'Disease', 'start': 249, 'end': 258, 'mesh': 'D003866'}, {'text': 'Dothiepin', 'type': 'Chemical', 'start': 272, 'end': 281, 'mesh': 'D004308'}, {'text': 'amitriptyline', 'type': 'Chemical', 'start': 286, 'end': 299, 'mesh': 'D000639'}, {'text': 'depressive illness', 'type': 'Disease', 'start': 354, 'end': 372, 'mesh': 'D003866'}, {'text': 'blurred vision', 'type': 'Disease', 'start': 495, 'end': 509, 'mesh': 'D014786'}, {'text': 'dry mouth', 'type': 'Disease', 'start': 511, 'end': 520, 'mesh': 'D014987'}, {'text': 'dothiepin', 'type': 'Chemical', 'start': 566, 'end': 575, 'mesh': 'D004308'}, {'text': 'amitriptyline', 'type': 'Chemical', 'start': 586, 'end': 599, 'mesh': 'D000639'}, {'text': 'Dothiepin', 'type': 'Chemical', 'start': 601, 'end': 610, 'mesh': 'D004308'}, {'text': 'Dothiepin', 'type': 'Chemical', 'start': 732, 'end': 741, 'mesh': 'D004308'}, {'text': 'antidepressant', 'type': 'Chemical', 'start': 776, 'end': 790, 'mesh': 'D000928'}, {'text': 'amitriptyline', 'type': 'Chemical', 'start': 836, 'end': 849, 'mesh': 'D000639'}, {'text': 'depressed', 'type': 'Disease', 'start': 870, 'end': 879, 'mesh': 'D003866'}]"
+34,6387529,Behavioral effects of diazepam and propranolol in patients with panic disorder and agoraphobia.,"The effects of oral doses of diazepam (single dose of 10 mg and a median dose of 30 mg/day for 2 weeks) and propranolol (single dose of 80 mg and a median dose of 240 mg/day for 2 weeks) on psychological performance of patients with panic disorders and agoraphobia were investigated in a double-blind, randomized and crossover design. Both drugs impaired immediate free recall but the decrease was greater for diazepam than propranolol. Delayed free recall was also impaired but the two drugs did not differ. Patients tapped faster after propranolol than diazepam and they were more sedated after diazepam than propranolol. After 2 weeks of treatment, patients tested 5-8 h after the last dose of medication did not show any decrement of performance. These results are similar to those previously found in healthy subjects. Accumulation of drugs was not reflected in prolonged behavioral impairment.","[{'text': 'diazepam', 'type': 'Chemical', 'start': 22, 'end': 30, 'mesh': 'D003975'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 35, 'end': 46, 'mesh': 'D011433'}, {'text': 'panic disorder', 'type': 'Disease', 'start': 64, 'end': 78, 'mesh': 'D016584'}, {'text': 'agoraphobia', 'type': 'Disease', 'start': 83, 'end': 94, 'mesh': 'D000379'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 125, 'end': 133, 'mesh': 'D003975'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 204, 'end': 215, 'mesh': 'D011433'}, {'text': 'panic disorders', 'type': 'Disease', 'start': 329, 'end': 344, 'mesh': 'D016584'}, {'text': 'agoraphobia', 'type': 'Disease', 'start': 349, 'end': 360, 'mesh': 'D000379'}, {'text': 'impaired immediate free recall', 'type': 'Disease', 'start': 442, 'end': 472, 'mesh': 'D008569'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 506, 'end': 514, 'mesh': 'D003975'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 520, 'end': 531, 'mesh': 'D011433'}, {'text': 'Delayed free recall was also impaired', 'type': 'Disease', 'start': 533, 'end': 570, 'mesh': 'D008569'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 634, 'end': 645, 'mesh': 'D011433'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 651, 'end': 659, 'mesh': 'D003975'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 693, 'end': 701, 'mesh': 'D003975'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 707, 'end': 718, 'mesh': 'D011433'}, {'text': 'behavioral impairment', 'type': 'Disease', 'start': 973, 'end': 994, 'mesh': 'D001523'}]"
+35,6692345,Effect of aspirin on N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide-induced epithelial proliferation in the urinary bladder and forestomach of the rat.,"The co-administration of aspirin with N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT) to rats resulted in a reduced incidence of FANFT-induced bladder carcinomas but a concomitant induction of forestomach tumors. An autoradiographic study was performed on male F-344 rats fed diet containing FANFT at a level of 0.2% and/or aspirin at a level of 0.5% to evaluate the effect of aspirin on the increased cell proliferation induced by FANFT in the forestomach and bladder. FANFT-induced cell proliferation in the bladder was significantly suppressed by aspirin co-administration after 4 weeks but not after 12 weeks. In the forestomach, and also in the liver, aspirin did not affect the FANFT-induced increase in labeling index. The present results are consistent with the carcinogenicity experiment suggesting that different mechanisms are involved in FANFT carcinogenesis in the bladder and forestomach, and that aspirin's effect on FANFT in the forestomach is not due to an irritant effect associated with increased cell proliferation. Also, there appears to be an adaptation by the rats to the chronic ingestion of aspirin.","[{'text': 'aspirin', 'type': 'Chemical', 'start': 10, 'end': 17, 'mesh': 'D001241'}, {'text': 'N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide', 'type': 'Chemical', 'start': 21, 'end': 66, 'mesh': 'D005200'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 176, 'end': 183, 'mesh': 'D001241'}, {'text': 'N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide', 'type': 'Chemical', 'start': 189, 'end': 234, 'mesh': 'D005200'}, {'text': 'FANFT', 'type': 'Chemical', 'start': 236, 'end': 241, 'mesh': 'D005200'}, {'text': 'FANFT', 'type': 'Chemical', 'start': 286, 'end': 291, 'mesh': 'D005200'}, {'text': 'bladder carcinomas', 'type': 'Disease', 'start': 300, 'end': 318, 'mesh': 'D001749'}, {'text': 'forestomach tumors', 'type': 'Disease', 'start': 350, 'end': 368, 'mesh': 'D013274'}, {'text': 'FANFT', 'type': 'Chemical', 'start': 449, 'end': 454, 'mesh': 'D005200'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 481, 'end': 488, 'mesh': 'D001241'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 534, 'end': 541, 'mesh': 'D001241'}, {'text': 'FANFT', 'type': 'Chemical', 'start': 589, 'end': 594, 'mesh': 'D005200'}, {'text': 'FANFT', 'type': 'Chemical', 'start': 627, 'end': 632, 'mesh': 'D005200'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 707, 'end': 714, 'mesh': 'D001241'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 814, 'end': 821, 'mesh': 'D001241'}, {'text': 'FANFT', 'type': 'Chemical', 'start': 841, 'end': 846, 'mesh': 'D005200'}, {'text': 'FANFT', 'type': 'Chemical', 'start': 1007, 'end': 1012, 'mesh': 'D005200'}, {'text': 'carcinogenesis', 'type': 'Disease', 'start': 1013, 'end': 1027, 'mesh': 'D063646'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1069, 'end': 1076, 'mesh': 'D001241'}, {'text': 'FANFT', 'type': 'Chemical', 'start': 1089, 'end': 1094, 'mesh': 'D005200'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1273, 'end': 1280, 'mesh': 'D001241'}]"
+36,6773726,Provocation of postural hypotension by nitroglycerin in diabetic autonomic neuropathy?,"The effect of nitroglycerin on heart rate and systolic blood pressure was compared in 5 normal subjects, 12 diabetic subjects without autonomic neuropathy, and 5 diabetic subjects with autonomic neuropathy. The magnitude and time course of the increase in heart rate and the decrease in systolic blood pressure after nitroglycerin were similar in the normal and diabetic subjects without autonomic neuropathy, whereas a lesser increase in heart rate and a greater decrease in systolic blood pressure occurred in the diabetic subjects with autonomic neuropathy. It is therefore suggested that caution should be exercised when prescribing vasodilator drugs in diabetic patients, particularly those with autonomic neuropathy.","[{'text': 'hypotension', 'type': 'Disease', 'start': 24, 'end': 35, 'mesh': 'D007022'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 39, 'end': 52, 'mesh': 'D005996'}, {'text': 'diabetic autonomic neuropathy', 'type': 'Disease', 'start': 56, 'end': 85, 'mesh': 'D003929'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 101, 'end': 114, 'mesh': 'D005996'}, {'text': 'diabetic', 'type': 'Disease', 'start': 195, 'end': 203, 'mesh': 'D003920'}, {'text': 'autonomic neuropathy', 'type': 'Disease', 'start': 221, 'end': 241, 'mesh': 'D009422'}, {'text': 'diabetic', 'type': 'Disease', 'start': 249, 'end': 257, 'mesh': 'D003920'}, {'text': 'autonomic neuropathy', 'type': 'Disease', 'start': 272, 'end': 292, 'mesh': 'D009422'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 404, 'end': 417, 'mesh': 'D005996'}, {'text': 'diabetic', 'type': 'Disease', 'start': 449, 'end': 457, 'mesh': 'D003920'}, {'text': 'autonomic neuropathy', 'type': 'Disease', 'start': 475, 'end': 495, 'mesh': 'D009422'}, {'text': 'diabetic', 'type': 'Disease', 'start': 603, 'end': 611, 'mesh': 'D003920'}, {'text': 'autonomic neuropathy', 'type': 'Disease', 'start': 626, 'end': 646, 'mesh': 'D009422'}, {'text': 'diabetic', 'type': 'Disease', 'start': 745, 'end': 753, 'mesh': 'D003920'}, {'text': 'autonomic neuropathy', 'type': 'Disease', 'start': 788, 'end': 808, 'mesh': 'D009422'}]"
+37,6888657,Characterization of estrogen-induced adenohypophyseal tumors in the Fischer 344 rat.,"Pituitary tumors were induced in F344 female rats by chronic treatment with diethylstilbestrol (DES, 8-10 mg) implanted subcutaneously in silastic capsules. Over a range of 1-150 days of DES treatment, pairs of control and DES-treated rats were sacrificed, and their pituitaries dissociated enzymatically into single-cell preparations. The cell populations were examined regarding total cell recovery correlated with gland weight, intracellular prolactin (PRL) content and subsequent release in primary culture, immunocytochemical PRL staining, density and/or size alterations via separation on Ficoll-Hypaque and by unit gravity sedimentation, and cell cycle analysis, after acriflavine DNA staining, by laser flow cytometry. Total cell yields from DES-treated pituitaries increased from 1.3 times control yields at 8 days of treatment to 58.9 times control values by day 150. Intracellular PRL content ranged from 1.9 to 9.4 times control levels, and PRL release in vitro was significantly and consistently higher than controls, after at least 8 days of DES exposure. Beyond 8 days of DES exposure, the immunochemically PRL-positive proportion of cells increased to over 50% of the total population. Increased density and/or size and PRL content were indicated for the majority of the PRL cell population in both types of separation protocols. All these effects of DES were more pronounced among previously ovariectomized animals. The data extend the findings of other investigators, further establishing the DES-induced tumor as a model for study of PRL cellular control mechanisms.","[{'text': 'estrogen', 'type': 'Chemical', 'start': 20, 'end': 28, 'mesh': 'D004967'}, {'text': 'adenohypophyseal tumors', 'type': 'Disease', 'start': 37, 'end': 60, 'mesh': 'D010911'}, {'text': 'Pituitary tumors', 'type': 'Disease', 'start': 85, 'end': 101, 'mesh': 'D010911'}, {'text': 'diethylstilbestrol', 'type': 'Chemical', 'start': 161, 'end': 179, 'mesh': 'D004054'}, {'text': 'DES', 'type': 'Chemical', 'start': 181, 'end': 184, 'mesh': 'D004054'}, {'text': 'DES', 'type': 'Chemical', 'start': 272, 'end': 275, 'mesh': 'D004054'}, {'text': 'DES', 'type': 'Chemical', 'start': 308, 'end': 311, 'mesh': 'D004054'}, {'text': 'acriflavine', 'type': 'Chemical', 'start': 761, 'end': 772, 'mesh': 'D000167'}, {'text': 'DES', 'type': 'Chemical', 'start': 835, 'end': 838, 'mesh': 'D004054'}, {'text': 'DES', 'type': 'Chemical', 'start': 1141, 'end': 1144, 'mesh': 'D004054'}, {'text': 'DES', 'type': 'Chemical', 'start': 1172, 'end': 1175, 'mesh': 'D004054'}, {'text': 'DES', 'type': 'Chemical', 'start': 1452, 'end': 1455, 'mesh': 'D004054'}, {'text': 'DES', 'type': 'Chemical', 'start': 1596, 'end': 1599, 'mesh': 'D004054'}, {'text': 'tumor', 'type': 'Disease', 'start': 1608, 'end': 1613, 'mesh': 'D009369'}]"
+38,7265370,Triamterene nephrolithiasis complicating dyazide therapy.,A case of triamterene nephrolithiasis is reported in a man after 4 years of hydrochlorothiazide-triamterene therapy for hypertension. The stone passed spontaneously and was found to contain a triamterene metabolite admixed with uric acid salts. Factors affecting triamterene nephrolithiasis are discussed and 2 previously reported cases are reviewed.,"[{'text': 'Triamterene', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D014223'}, {'text': 'nephrolithiasis', 'type': 'Disease', 'start': 12, 'end': 27, 'mesh': 'D053040'}, {'text': 'dyazide', 'type': 'Chemical', 'start': 41, 'end': 48, 'mesh': 'C020743'}, {'text': 'triamterene', 'type': 'Chemical', 'start': 68, 'end': 79, 'mesh': 'D014223'}, {'text': 'nephrolithiasis', 'type': 'Disease', 'start': 80, 'end': 95, 'mesh': 'D053040'}, {'text': 'hydrochlorothiazide-triamterene', 'type': 'Chemical', 'start': 134, 'end': 165, 'mesh': 'C020743'}, {'text': 'hypertension', 'type': 'Disease', 'start': 178, 'end': 190, 'mesh': 'D006973'}, {'text': 'triamterene', 'type': 'Chemical', 'start': 250, 'end': 261, 'mesh': 'D014223'}, {'text': 'uric acid salts', 'type': 'Chemical', 'start': 286, 'end': 301, 'mesh': 'D014527|D012492'}, {'text': 'triamterene', 'type': 'Chemical', 'start': 321, 'end': 332, 'mesh': 'D014223'}, {'text': 'nephrolithiasis', 'type': 'Disease', 'start': 333, 'end': 348, 'mesh': 'D053040'}]"
+39,7423039,Metabolic involvement in adriamycin cardiotoxicity.,"The cardiotoxic effects of adriamycin were studied in mammalian myocardial cells in culture as a model system. Adriamycin inhibited cell growth and the rhythmic contractions characteristic of myocardial cells in culture. A possible involvement of energy metabolism was suggested previously, and in this study the adenylate energy charge and phosphorylcreatine mole fraction were determined in the adriamycin-treated cells. The adenylate energy charge was found to be significantly decreased, while the phophorylcreatine mole fraction was unchanged. Such disparity suggests an inhibition of creatine phosphokinase. The addition of 1 mM adenosine to the myocardial cell cultures markedly increases the ATP concentration through a pathway reportedly leading to a compartmentalized ATP pool. In the adriamycin-treated cells, the addition of adenosine increased the adenylate charge and, concomitant with this inrcease, the cells' functional integrity, in terms of percentage of beating cells and rate of contractions, was maintained.","[{'text': 'adriamycin', 'type': 'Chemical', 'start': 25, 'end': 35, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 36, 'end': 50, 'mesh': 'D066126'}, {'text': 'cardiotoxic', 'type': 'Disease', 'start': 56, 'end': 67, 'mesh': 'D066126'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 79, 'end': 89, 'mesh': 'D004317'}, {'text': 'Adriamycin', 'type': 'Chemical', 'start': 163, 'end': 173, 'mesh': 'D004317'}, {'text': 'phosphorylcreatine', 'type': 'Chemical', 'start': 393, 'end': 411, 'mesh': 'D010725'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 449, 'end': 459, 'mesh': 'D004317'}, {'text': 'phophorylcreatine', 'type': 'Chemical', 'start': 554, 'end': 571, 'mesh': 'D010725'}, {'text': 'creatine', 'type': 'Chemical', 'start': 642, 'end': 650, 'mesh': 'D003401'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 687, 'end': 696, 'mesh': 'D000241'}, {'text': 'ATP', 'type': 'Chemical', 'start': 752, 'end': 755, 'mesh': 'D000255'}, {'text': 'ATP', 'type': 'Chemical', 'start': 830, 'end': 833, 'mesh': 'D000255'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 847, 'end': 857, 'mesh': 'D004317'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 889, 'end': 898, 'mesh': 'D000241'}]"
+40,7444978,Age-dependent sensitivity of the rat to neurotoxic effects of streptomycin.,"Streptomycin sulfate (300 mg/kg s.c.) was injected for various periods into preweanling rats and for 3 weeks into weanling rats. Beginning at 8 days of age, body movement and hearing were examined for 6 and up to 17 weeks, respectively. Abnormal movements and deafness occurred only in rats treated during the preweaning period; within this period the greatest sensitivities for these abnormalities occurred from 2 to 11-17 and 5 to 11 days of age, respectively, indicating that the cochlea is more sensitive to streptomycin than the site (vestibular or central) responsible for the dyskinesias.","[{'text': 'neurotoxic', 'type': 'Disease', 'start': 40, 'end': 50, 'mesh': 'D020258'}, {'text': 'streptomycin', 'type': 'Chemical', 'start': 62, 'end': 74, 'mesh': 'D013307'}, {'text': 'Streptomycin', 'type': 'Chemical', 'start': 76, 'end': 88, 'mesh': 'D013307'}, {'text': 'Abnormal movements', 'type': 'Disease', 'start': 313, 'end': 331, 'mesh': 'D004409'}, {'text': 'deafness', 'type': 'Disease', 'start': 336, 'end': 344, 'mesh': 'D003638'}, {'text': 'streptomycin', 'type': 'Chemical', 'start': 588, 'end': 600, 'mesh': 'D013307'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 659, 'end': 670, 'mesh': 'D004409'}]"
+41,7834920,Crescentic fibrillary glomerulonephritis associated with intermittent rifampin therapy for pulmonary tuberculosis.,"This case study reveals an unusual finding of rapidly proliferative crescentic glomerulonephritis in a patient treated with rifampin who had no other identifiable causes for developing this disease. This patient underwent a 10-month regimen of rifampin and isoniazid for pulmonary tuberculosis and was discovered to have developed signs of severe renal failure five weeks after completion of therapy. Renal biopsy revealed severe glomerulonephritis with crescents, electron dense fibrillar deposits and moderate lymphocytic interstitial infiltrate. Other possible causes of rapidly progressive glomerulonephritis were investigated and ruled out. This report documents the unusual occurrence of rapidly progressive glomerulonephritis with crescents and fibrillar glomerulonephritis in a patient treated with rifampin.","[{'text': 'glomerulonephritis', 'type': 'Disease', 'start': 22, 'end': 40, 'mesh': 'D005921'}, {'text': 'rifampin', 'type': 'Chemical', 'start': 70, 'end': 78, 'mesh': 'D012293'}, {'text': 'pulmonary tuberculosis', 'type': 'Disease', 'start': 91, 'end': 113, 'mesh': 'D014397'}, {'text': 'glomerulonephritis', 'type': 'Disease', 'start': 194, 'end': 212, 'mesh': 'D005921'}, {'text': 'rifampin', 'type': 'Chemical', 'start': 239, 'end': 247, 'mesh': 'D012293'}, {'text': 'rifampin', 'type': 'Chemical', 'start': 359, 'end': 367, 'mesh': 'D012293'}, {'text': 'isoniazid', 'type': 'Chemical', 'start': 372, 'end': 381, 'mesh': 'D007538'}, {'text': 'pulmonary tuberculosis', 'type': 'Disease', 'start': 386, 'end': 408, 'mesh': 'D014397'}, {'text': 'renal failure', 'type': 'Disease', 'start': 462, 'end': 475, 'mesh': 'D051437'}, {'text': 'glomerulonephritis', 'type': 'Disease', 'start': 545, 'end': 563, 'mesh': 'D005921'}, {'text': 'glomerulonephritis', 'type': 'Disease', 'start': 709, 'end': 727, 'mesh': 'D005921'}, {'text': 'glomerulonephritis', 'type': 'Disease', 'start': 829, 'end': 847, 'mesh': 'D005921'}, {'text': 'glomerulonephritis', 'type': 'Disease', 'start': 877, 'end': 895, 'mesh': 'D005921'}, {'text': 'rifampin', 'type': 'Chemical', 'start': 922, 'end': 930, 'mesh': 'D012293'}]"
+42,7881871,Time course of lipid peroxidation in puromycin aminonucleoside-induced nephropathy.,"Reactive oxygen species have been implicated in the pathogenesis of acute puromycin aminonucleoside (PAN)-induced nephropathy, with antioxidants significantly reducing the proteinuria. The temporal relationship between lipid peroxidation in the kidney and proteinuria was examined in this study. Rats were treated with a single IV injection of puromycin aminonucleoside, (PAN, 7.5 mg/kg) and 24 hour urine samples were obtained prior to sacrifice on days 3,5,7,10,17,27,41 (N = 5-10 per group). The kidneys were removed, flushed with ice cold TRIS buffer. Kidney cortices from each animal were used to prepare homogenates. Tissue lipid peroxidation was measured in whole homogenates as well as in lipid extracts from homogenates as thiobarbituric acid reactive substances. Proteinuria was evident at day 5, peaked at day 7 and persisted to day 27. Lipid peroxidation in homogenates was maximal at day 3 and declined rapidly to control levels by day 17. This study supports the role of lipid peroxidation in mediating the proteinuric injury in PAN nephropathy.","[{'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 37, 'end': 62, 'mesh': 'D011692'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 71, 'end': 82, 'mesh': 'D007674'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 93, 'end': 99, 'mesh': 'D010100'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 158, 'end': 183, 'mesh': 'D011692'}, {'text': 'PAN', 'type': 'Chemical', 'start': 185, 'end': 188, 'mesh': 'D011692'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 198, 'end': 209, 'mesh': 'D007674'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 256, 'end': 267, 'mesh': 'D011507'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 340, 'end': 351, 'mesh': 'D011507'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 428, 'end': 453, 'mesh': 'D011692'}, {'text': 'PAN', 'type': 'Chemical', 'start': 456, 'end': 459, 'mesh': 'D011692'}, {'text': 'thiobarbituric acid', 'type': 'Chemical', 'start': 816, 'end': 835, 'mesh': 'C029684'}, {'text': 'Proteinuria', 'type': 'Disease', 'start': 857, 'end': 868, 'mesh': 'D011507'}, {'text': 'proteinuric injury', 'type': 'Disease', 'start': 1105, 'end': 1123, 'mesh': 'D011507'}, {'text': 'PAN', 'type': 'Chemical', 'start': 1127, 'end': 1130, 'mesh': 'D011692'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1131, 'end': 1142, 'mesh': 'D007674'}]"
+43,7930386,Clomipramine-induced sleep disturbance does not impair its prolactin-releasing action.,"The present study was undertaken to examine the role of sleep disturbance, induced by clomipramine administration, on the secretory rate of prolactin (PRL) in addition to the direct drug effect. Two groups of supine subjects were studied under placebo-controlled conditions, one during the night, when sleeping (n = 7) and the other at daytime, when awake (n = 6). Each subject received a single 50 mg dose of clomipramine given orally 2 hours before blood collection. Plasma PRL concentrations were analysed at 10 min intervals and underlying secretory rates calculated by a deconvolution procedure. For both experiments the drug intake led to significant increases in PRL secretion, acting preferentially on tonic secretion as pulse amplitude and frequency did not differ significantly from corresponding control values. During the night clomipramine ingestion altered the complete sleep architecture in that it suppressed REM sleep and the sleep cycles and induced increased wakefulness. As the relative increase in PRL secretion expressed as a percentage of the mean did not significantly differ between the night and day time studies (46 +/- 19% vs 34 +/- 10%), it can be concluded that the observed sleep disturbance did not interfere with the drug action per se. The presence of REM sleep was shown not to be a determining factor either for secretory pulse amplitude and frequency, as, for both, mean nocturnal values were similar with and without prior clomipramine ingestion.","[{'text': 'Clomipramine', 'type': 'Chemical', 'start': 0, 'end': 12, 'mesh': 'D002997'}, {'text': 'sleep disturbance', 'type': 'Disease', 'start': 21, 'end': 38, 'mesh': 'D012893'}, {'text': 'sleep disturbance', 'type': 'Disease', 'start': 143, 'end': 160, 'mesh': 'D012893'}, {'text': 'clomipramine', 'type': 'Chemical', 'start': 173, 'end': 185, 'mesh': 'D002997'}, {'text': 'clomipramine', 'type': 'Chemical', 'start': 497, 'end': 509, 'mesh': 'D002997'}, {'text': 'clomipramine', 'type': 'Chemical', 'start': 927, 'end': 939, 'mesh': 'D002997'}, {'text': 'sleep disturbance', 'type': 'Disease', 'start': 1292, 'end': 1309, 'mesh': 'D012893'}, {'text': 'clomipramine', 'type': 'Chemical', 'start': 1548, 'end': 1560, 'mesh': 'D002997'}]"
+44,7988234,Angioedema following the intravenous administration of metoprolol.,"A 72-year-old woman was admitted to the hospital with ""flash"" pulmonary edema, preceded by chest pain, requiring intubation. Her medical history included coronary artery disease with previous myocardial infarctions, hypertension, and diabetes mellitus. A history of angioedema secondary to lisinopril therapy was elicited. Current medications did not include angiotensin-converting enzyme inhibitors or beta-blockers. She had no previous beta-blocking drug exposure. During the first day of hospitalization (while intubated), intravenous metoprolol was given, resulting in severe angioedema. The angioedema resolved after therapy with intravenous steroids and diphenhydramine hydrochloride.","[{'text': 'Angioedema', 'type': 'Disease', 'start': 0, 'end': 10, 'mesh': 'D000799'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 55, 'end': 65, 'mesh': 'D008790'}, {'text': 'pulmonary edema', 'type': 'Disease', 'start': 129, 'end': 144, 'mesh': 'D011654'}, {'text': 'chest pain', 'type': 'Disease', 'start': 158, 'end': 168, 'mesh': 'D002637'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 221, 'end': 244, 'mesh': 'D003324'}, {'text': 'myocardial infarctions', 'type': 'Disease', 'start': 259, 'end': 281, 'mesh': 'D009203'}, {'text': 'hypertension', 'type': 'Disease', 'start': 283, 'end': 295, 'mesh': 'D006973'}, {'text': 'diabetes mellitus', 'type': 'Disease', 'start': 301, 'end': 318, 'mesh': 'D003920'}, {'text': 'angioedema', 'type': 'Disease', 'start': 333, 'end': 343, 'mesh': 'D000799'}, {'text': 'lisinopril', 'type': 'Chemical', 'start': 357, 'end': 367, 'mesh': 'D017706'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 426, 'end': 437, 'mesh': 'D000809'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 605, 'end': 615, 'mesh': 'D008790'}, {'text': 'angioedema', 'type': 'Disease', 'start': 647, 'end': 657, 'mesh': 'D000799'}, {'text': 'angioedema', 'type': 'Disease', 'start': 663, 'end': 673, 'mesh': 'D000799'}, {'text': 'steroids', 'type': 'Chemical', 'start': 714, 'end': 722, 'mesh': 'D013256'}, {'text': 'diphenhydramine', 'type': 'Chemical', 'start': 727, 'end': 742, 'mesh': 'D004155'}]"
+45,8073369,Effect of coniine on the developing chick embryo.,"Coniine, an alkaloid from Conium maculatum (poison hemlock), has been shown to be teratogenic in livestock. The major teratogenic outcome is arthrogryposis, presumably due to nicotinic receptor blockade. However, coniine has failed to produce arthrogryposis in rats or mice and is only weakly teratogenic in rabbits. The purpose of this study was to evaluate and compare the effects of coniine and nicotine in the developing chick. Concentrations of coniine and nicotine sulfate were 0.015%, 0.03%, 0.075%, 0.15%, 0.75%, 1.5%, 3%, and 6% and 1%, 5%, and 10%, respectively. Both compounds caused deformations and lethality in a dose-dependent manner. All concentrations of nicotine sulfate caused some lethality but a no effect level for coniine lethality was 0.75%. The deformations caused by both coniine and nicotine sulfate were excessive flexion or extension of one or more toes. No histopathological alterations or differences in bone formation were seen in the limbs or toes of any chicks from any group; however, extensive cranial hemorrhage occurred in all nicotine sulfate-treated chicks. There was a statistically significant (P < or = 0.01) decrease in movement in coniine and nicotine sulfate treated chicks as determined by ultrasound. Control chicks were in motion an average of 33.67% of the time, while coniine-treated chicks were only moving 8.95% of a 5-min interval, and no movement was observed for nicotine sulfate treated chicks. In summary, the chick embryo provides a reliable and simple experimental animal model of coniine-induced arthrogryposis. Data from this model support a mechanism involving nicotinic receptor blockade with subsequent decreased fetal movement.","[{'text': 'coniine', 'type': 'Chemical', 'start': 10, 'end': 17, 'mesh': 'C007112'}, {'text': 'Coniine', 'type': 'Chemical', 'start': 50, 'end': 57, 'mesh': 'C007112'}, {'text': 'arthrogryposis', 'type': 'Disease', 'start': 191, 'end': 205, 'mesh': 'D001176'}, {'text': 'coniine', 'type': 'Chemical', 'start': 263, 'end': 270, 'mesh': 'C007112'}, {'text': 'arthrogryposis', 'type': 'Disease', 'start': 293, 'end': 307, 'mesh': 'D001176'}, {'text': 'coniine', 'type': 'Chemical', 'start': 436, 'end': 443, 'mesh': 'C007112'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 448, 'end': 456, 'mesh': 'D009538'}, {'text': 'coniine', 'type': 'Chemical', 'start': 500, 'end': 507, 'mesh': 'C007112'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 512, 'end': 520, 'mesh': 'D009538'}, {'text': 'deformations', 'type': 'Disease', 'start': 645, 'end': 657, 'mesh': 'D009140'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 722, 'end': 730, 'mesh': 'D009538'}, {'text': 'coniine', 'type': 'Chemical', 'start': 787, 'end': 794, 'mesh': 'C007112'}, {'text': 'deformations', 'type': 'Disease', 'start': 820, 'end': 832, 'mesh': 'D009140'}, {'text': 'coniine', 'type': 'Chemical', 'start': 848, 'end': 855, 'mesh': 'C007112'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 860, 'end': 868, 'mesh': 'D009538'}, {'text': 'excessive flexion or extension of one or more toes', 'type': 'Disease', 'start': 882, 'end': 932, 'mesh': 'D009140'}, {'text': 'cranial hemorrhage', 'type': 'Disease', 'start': 1080, 'end': 1098, 'mesh': 'D002543'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 1115, 'end': 1123, 'mesh': 'D009538'}, {'text': 'coniine', 'type': 'Chemical', 'start': 1226, 'end': 1233, 'mesh': 'C007112'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 1238, 'end': 1246, 'mesh': 'D009538'}, {'text': 'coniine', 'type': 'Chemical', 'start': 1369, 'end': 1376, 'mesh': 'C007112'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 1469, 'end': 1477, 'mesh': 'D009538'}, {'text': 'coniine', 'type': 'Chemical', 'start': 1591, 'end': 1598, 'mesh': 'C007112'}, {'text': 'arthrogryposis', 'type': 'Disease', 'start': 1607, 'end': 1621, 'mesh': 'D001176'}]"
+46,8302922,Epidural blood flow during prostaglandin E1 or trimethaphan induced hypotension.,"To evaluate the effect of prostaglandin E1 (PGE1) or trimethaphan (TMP) induced hypotension on epidural blood flow (EBF) during spinal surgery, EBF was measured using the heat clearance method in 30 patients who underwent postero-lateral interbody fusion under isoflurane anaesthesia. An initial dose of 0.1 microgram.kg-1.min-1 of PGE1 (15 patients), or 10 micrograms.kg-1.min-1 of TMP (15 patients) was administered intravenously after the dural opening and the dose was adjusted to maintain the mean arterial blood pressure (MAP) at about 60 mmHg. The hypotensive drug was discontinued at the completion of the operative procedure. After starting PGE1 or TMP, MAP and rate pressure product (RPP) decreased significantly compared with preinfusion values (P < 0.01), and the degree of hypotension due to PGE1 remained constant until 60 min after its discontinuation. Heart rate (HR) did not change in either group. EBFF did not change during PGE1 infusion whereas in the TMP group, EBF decreased significantly at 30 and 60 min after the start of TMP (preinfusion: 45.9 +/- 13.9 ml/100g/min. 30 min: 32.3 +/- 9.9 ml/100 g/min (P < 0.05). 60 min: 30 +/- 7.5 ml/100 g/min (P < 0.05)). These results suggest that PGE1 may be preferable to TMP for hypotensive anaesthesia in spinal surgery because TMP decreased EBF.","[{'text': 'prostaglandin E1', 'type': 'Chemical', 'start': 27, 'end': 43, 'mesh': 'D000527'}, {'text': 'trimethaphan', 'type': 'Chemical', 'start': 47, 'end': 59, 'mesh': 'D014294'}, {'text': 'hypotension', 'type': 'Disease', 'start': 68, 'end': 79, 'mesh': 'D007022'}, {'text': 'prostaglandin E1', 'type': 'Chemical', 'start': 107, 'end': 123, 'mesh': 'D000527'}, {'text': 'PGE1', 'type': 'Chemical', 'start': 125, 'end': 129, 'mesh': 'D000527'}, {'text': 'trimethaphan', 'type': 'Chemical', 'start': 134, 'end': 146, 'mesh': 'D014294'}, {'text': 'TMP', 'type': 'Chemical', 'start': 148, 'end': 151, 'mesh': 'D014294'}, {'text': 'hypotension', 'type': 'Disease', 'start': 161, 'end': 172, 'mesh': 'D007022'}, {'text': 'isoflurane', 'type': 'Chemical', 'start': 342, 'end': 352, 'mesh': 'D007530'}, {'text': 'PGE1', 'type': 'Chemical', 'start': 413, 'end': 417, 'mesh': 'D000527'}, {'text': 'TMP', 'type': 'Chemical', 'start': 464, 'end': 467, 'mesh': 'D014294'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 636, 'end': 647, 'mesh': 'D007022'}, {'text': 'PGE1', 'type': 'Chemical', 'start': 731, 'end': 735, 'mesh': 'D000527'}, {'text': 'TMP', 'type': 'Chemical', 'start': 739, 'end': 742, 'mesh': 'D014294'}, {'text': 'hypotension', 'type': 'Disease', 'start': 867, 'end': 878, 'mesh': 'D007022'}, {'text': 'PGE1', 'type': 'Chemical', 'start': 886, 'end': 890, 'mesh': 'D000527'}, {'text': 'PGE1', 'type': 'Chemical', 'start': 1024, 'end': 1028, 'mesh': 'D000527'}, {'text': 'TMP', 'type': 'Chemical', 'start': 1053, 'end': 1056, 'mesh': 'D014294'}, {'text': 'TMP', 'type': 'Chemical', 'start': 1128, 'end': 1131, 'mesh': 'D014294'}, {'text': 'PGE1', 'type': 'Chemical', 'start': 1291, 'end': 1295, 'mesh': 'D000527'}, {'text': 'TMP', 'type': 'Chemical', 'start': 1317, 'end': 1320, 'mesh': 'D014294'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 1325, 'end': 1336, 'mesh': 'D007022'}, {'text': 'TMP', 'type': 'Chemical', 'start': 1375, 'end': 1378, 'mesh': 'D014294'}]"
+47,8410052,Immunohistochemical studies with antibodies to neurofilament proteins on axonal damage in experimental focal lesions in rat.,"Immunohistochemistry with monoclonal antibodies against neurofilament (NF) proteins of middle and high molecular weight class, NF-M and NF-H, was used to study axonal injury in the borderzone of focal lesions in rats. Focal injury in the cortex was produced by infusion of lactate at acid pH or by stab caused by needle insertion. Infarcts in substantia nigra pars reticulata were evoked by prolonged pilocarpine-induced status epilepticus. Immunohistochemical staining for NFs showed characteristic terminal clubs of axons in the borderzone of lesions. Differences in the labelling pattern occurred with different antibodies which apparently depended on molecular weight class of NFs and phosphorylation state. These immunohistochemical changes of NFs can serve as a marker for axonal damage in various experimental traumatic or ischemic lesions.","[{'text': 'axonal damage', 'type': 'Disease', 'start': 73, 'end': 86, 'mesh': 'D001480'}, {'text': 'axonal injury', 'type': 'Disease', 'start': 285, 'end': 298, 'mesh': 'D001480'}, {'text': 'injury in the cortex', 'type': 'Disease', 'start': 349, 'end': 369, 'mesh': 'D001480'}, {'text': 'lactate', 'type': 'Chemical', 'start': 398, 'end': 405, 'mesh': 'D019344'}, {'text': 'Infarcts in substantia nigra pars reticulata', 'type': 'Disease', 'start': 456, 'end': 500, 'mesh': 'D002544'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 526, 'end': 537, 'mesh': 'D010862'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 546, 'end': 564, 'mesh': 'D013226'}, {'text': 'axonal damage', 'type': 'Disease', 'start': 904, 'end': 917, 'mesh': 'D001480'}, {'text': 'traumatic', 'type': 'Disease', 'start': 942, 'end': 951, 'mesh': 'D014947'}]"
+48,8423889,Increase of Parkinson disability after fluoxetine medication.,Depression is a major clinical feature of Parkinson's disease. We report the increased amount of motor disability in four patients with idiopathic Parkinson's disease after exposure to the antidepressant fluoxetine. The possibility of a clinically relevant dopamine-antagonistic capacity of fluoxetine in Parkinson's disease patients must be considered.,"[{'text': 'Parkinson disability', 'type': 'Disease', 'start': 12, 'end': 32, 'mesh': 'D009069'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 39, 'end': 49, 'mesh': 'D005473'}, {'text': 'Depression', 'type': 'Disease', 'start': 62, 'end': 72, 'mesh': 'D003866'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 104, 'end': 123, 'mesh': 'D010300'}, {'text': 'motor disability', 'type': 'Disease', 'start': 159, 'end': 175, 'mesh': 'D009069'}, {'text': ""idiopathic Parkinson's disease"", 'type': 'Disease', 'start': 198, 'end': 228, 'mesh': 'D010300'}, {'text': 'antidepressant', 'type': 'Chemical', 'start': 251, 'end': 265, 'mesh': 'D000928'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 266, 'end': 276, 'mesh': 'D005473'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 319, 'end': 327, 'mesh': 'D004298'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 353, 'end': 363, 'mesh': 'D005473'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 367, 'end': 386, 'mesh': 'D010300'}]"
+49,8682684,Acetaminophen-induced hypotension.,"Through 30 years of widespread use, acetaminophen has been shown to be a remarkably safe medication in therapeutic dosages. The potential for acetaminophen to produce cardiovascular toxicities is very low. However, acetaminophen has been demonstrated to produce symptoms of anaphylaxis, including hypotension, in sensitive individuals. This article describes two critically ill patients in whom transient episodes of hypotension reproducibly developed after administration of acetaminophen. Other symptoms of allergic reactions were not clinically detectable. The hypotensive episodes were severe enough to require vasopressor administration. The reports illustrate the need for clinicians to consider acetaminophen in patients with hypotension of unknown origin.","[{'text': 'Acetaminophen', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'D000082'}, {'text': 'hypotension', 'type': 'Disease', 'start': 22, 'end': 33, 'mesh': 'D007022'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 71, 'end': 84, 'mesh': 'D000082'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 177, 'end': 190, 'mesh': 'D000082'}, {'text': 'cardiovascular toxicities', 'type': 'Disease', 'start': 202, 'end': 227, 'mesh': 'D002318'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 250, 'end': 263, 'mesh': 'D000082'}, {'text': 'anaphylaxis', 'type': 'Disease', 'start': 309, 'end': 320, 'mesh': 'D000707'}, {'text': 'hypotension', 'type': 'Disease', 'start': 332, 'end': 343, 'mesh': 'D007022'}, {'text': 'critically ill', 'type': 'Disease', 'start': 398, 'end': 412, 'mesh': 'D016638'}, {'text': 'hypotension', 'type': 'Disease', 'start': 452, 'end': 463, 'mesh': 'D007022'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 511, 'end': 524, 'mesh': 'D000082'}, {'text': 'allergic reactions', 'type': 'Disease', 'start': 544, 'end': 562, 'mesh': 'D004342'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 599, 'end': 610, 'mesh': 'D007022'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 737, 'end': 750, 'mesh': 'D000082'}, {'text': 'hypotension', 'type': 'Disease', 'start': 768, 'end': 779, 'mesh': 'D007022'}]"
+50,9625142,"Acute hepatitis, autoimmune hemolytic anemia, and erythroblastocytopenia induced by ceftriaxone.","An 80-yr-old man developed acute hepatitis shortly after ingesting oral ceftriaxone. Although the transaminases gradually returned to baseline after withholding the beta lactam antibiotic, there was a gradual increase in serum bilirubin and a decrease in hemoglobin concentration caused by an autoimmune hemolytic anemia and erythroblastocytopenia. These responded to systemic steroids and immunoglobulins. Despite the widespread use of these agents this triad of side effects has not previously been reported in connection with beta lactam antibiotics.","[{'text': 'hepatitis', 'type': 'Disease', 'start': 6, 'end': 15, 'mesh': 'D056486'}, {'text': 'autoimmune hemolytic anemia', 'type': 'Disease', 'start': 17, 'end': 44, 'mesh': 'D000744'}, {'text': 'erythroblastocytopenia', 'type': 'Disease', 'start': 50, 'end': 72, 'mesh': '-1'}, {'text': 'ceftriaxone', 'type': 'Chemical', 'start': 84, 'end': 95, 'mesh': 'D002443'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 130, 'end': 139, 'mesh': 'D056486'}, {'text': 'ceftriaxone', 'type': 'Chemical', 'start': 169, 'end': 180, 'mesh': 'D002443'}, {'text': 'beta lactam', 'type': 'Chemical', 'start': 262, 'end': 273, 'mesh': 'D047090'}, {'text': 'bilirubin', 'type': 'Chemical', 'start': 324, 'end': 333, 'mesh': 'D001663'}, {'text': 'autoimmune hemolytic anemia', 'type': 'Disease', 'start': 390, 'end': 417, 'mesh': 'D000744'}, {'text': 'erythroblastocytopenia', 'type': 'Disease', 'start': 422, 'end': 444, 'mesh': '-1'}, {'text': 'steroids', 'type': 'Chemical', 'start': 474, 'end': 482, 'mesh': 'D013256'}, {'text': 'beta lactam', 'type': 'Chemical', 'start': 626, 'end': 637, 'mesh': 'D047090'}]"
+51,9766615,Adverse effects of the atypical antipsychotics. Collaborative Working Group on Clinical Trial Evaluations.,"Adverse effects of antipsychotics often lead to noncompliance. Thus, clinicians should address patients' concerns about adverse effects and attempt to choose medications that will improve their patients' quality of life as well as overall health. The side effect profiles of the atypical antipsychotics are more advantageous than those of the conventional neuroleptics. Conventional agents are associated with unwanted central nervous system effects, including extrapyramidal symptoms (EPS), tardive dyskinesia, sedation, and possible impairment of some cognitive measures, as well as cardiac effects, orthostatic hypotension, hepatic changes, anticholinergic side effects, sexual dysfunction, and weight gain. The newer atypical agents have a lower risk of EPS, but are associated in varying degrees with sedation, cardiovascular effects, anticholinergic effects, weight gain, sexual dysfunction, hepatic effects, lowered seizure threshold (primarily clozapine), and agranulocytosis (clozapine only). Since the incidence and severity of specific adverse effects differ among the various atypicals, the clinician should carefully consider which side effects are most likely to lead to the individual's dissatisfaction and noncompliance before choosing an antipsychotic for a particular patient.","[{'text': 'extrapyramidal symptoms', 'type': 'Disease', 'start': 568, 'end': 591, 'mesh': 'D001480'}, {'text': 'EPS', 'type': 'Disease', 'start': 593, 'end': 596, 'mesh': 'D001480'}, {'text': 'tardive dyskinesia', 'type': 'Disease', 'start': 599, 'end': 617, 'mesh': 'D004409'}, {'text': 'orthostatic hypotension', 'type': 'Disease', 'start': 709, 'end': 732, 'mesh': 'D007024'}, {'text': 'sexual dysfunction', 'type': 'Disease', 'start': 781, 'end': 799, 'mesh': 'D012735'}, {'text': 'weight gain', 'type': 'Disease', 'start': 805, 'end': 816, 'mesh': 'D015430'}, {'text': 'EPS', 'type': 'Disease', 'start': 865, 'end': 868, 'mesh': 'D001480'}, {'text': 'weight gain', 'type': 'Disease', 'start': 972, 'end': 983, 'mesh': 'D015430'}, {'text': 'sexual dysfunction', 'type': 'Disease', 'start': 985, 'end': 1003, 'mesh': 'D012735'}, {'text': 'seizure', 'type': 'Disease', 'start': 1030, 'end': 1037, 'mesh': 'D012640'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 1059, 'end': 1068, 'mesh': 'D003024'}, {'text': 'agranulocytosis', 'type': 'Disease', 'start': 1075, 'end': 1090, 'mesh': 'D000380'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 1092, 'end': 1101, 'mesh': 'D003024'}]"
+52,10193204,Effects of tetrandrine and fangchinoline on experimental thrombosis in mice and human platelet aggregation.,"Tetrandrine (TET) and fangchinoline (FAN) are two naturally occurring analogues with a bisbenzylisoquinoline structure. The present study was undertaken to investigate the effects of TET and FAN on the experimental thrombosis induced by collagen plus epinephrine (EP) in mice, and platelet aggregation and blood coagulation in vitro. In the in vivo study, the administration (50 mg/kg, i.p.) of TET and FAN in mice showed the inhibition of thrombosis by 55% and 35%, respectively, while acetylsalicylic acid (ASA, 50 mg/kg, i.p.), a positive control, showed only 30% inhibition. In the vitro human platelet aggregations induced by the agonists used in tests, TET and FAN showed the inhibitions dose dependently. In addition, neither TET nor FAN showed any anticoagulation activities in the measurement of the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using human-citrated plasma. These results suggest that antithrombosis of TET and FAN in mice may be mainly related to the antiplatelet aggregation activities.","[{'text': 'tetrandrine', 'type': 'Chemical', 'start': 11, 'end': 22, 'mesh': 'C009438'}, {'text': 'fangchinoline', 'type': 'Chemical', 'start': 27, 'end': 40, 'mesh': 'C060802'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 57, 'end': 67, 'mesh': 'D013927'}, {'text': 'platelet aggregation', 'type': 'Disease', 'start': 86, 'end': 106, 'mesh': 'D001791'}, {'text': 'Tetrandrine', 'type': 'Chemical', 'start': 108, 'end': 119, 'mesh': 'C009438'}, {'text': 'TET', 'type': 'Chemical', 'start': 121, 'end': 124, 'mesh': 'C009438'}, {'text': 'fangchinoline', 'type': 'Chemical', 'start': 130, 'end': 143, 'mesh': 'C060802'}, {'text': 'FAN', 'type': 'Chemical', 'start': 145, 'end': 148, 'mesh': 'C060802'}, {'text': 'bisbenzylisoquinoline', 'type': 'Chemical', 'start': 195, 'end': 216, 'mesh': 'D044182'}, {'text': 'TET', 'type': 'Chemical', 'start': 291, 'end': 294, 'mesh': 'C009438'}, {'text': 'FAN', 'type': 'Chemical', 'start': 299, 'end': 302, 'mesh': 'C060802'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 323, 'end': 333, 'mesh': 'D013927'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 359, 'end': 370, 'mesh': 'D004837'}, {'text': 'EP', 'type': 'Chemical', 'start': 372, 'end': 374, 'mesh': 'D004837'}, {'text': 'platelet aggregation', 'type': 'Disease', 'start': 389, 'end': 409, 'mesh': 'D001791'}, {'text': 'blood coagulation', 'type': 'Disease', 'start': 414, 'end': 431, 'mesh': 'D001778'}, {'text': 'TET', 'type': 'Chemical', 'start': 503, 'end': 506, 'mesh': 'C009438'}, {'text': 'FAN', 'type': 'Chemical', 'start': 511, 'end': 514, 'mesh': 'C060802'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 548, 'end': 558, 'mesh': 'D013927'}, {'text': 'acetylsalicylic acid', 'type': 'Chemical', 'start': 595, 'end': 615, 'mesh': 'D001241'}, {'text': 'ASA', 'type': 'Chemical', 'start': 617, 'end': 620, 'mesh': 'D001241'}, {'text': 'platelet aggregations', 'type': 'Disease', 'start': 706, 'end': 727, 'mesh': 'D001791'}, {'text': 'TET', 'type': 'Chemical', 'start': 767, 'end': 770, 'mesh': 'C009438'}, {'text': 'FAN', 'type': 'Chemical', 'start': 775, 'end': 778, 'mesh': 'C060802'}, {'text': 'TET', 'type': 'Chemical', 'start': 841, 'end': 844, 'mesh': 'C009438'}, {'text': 'FAN', 'type': 'Chemical', 'start': 849, 'end': 852, 'mesh': 'C060802'}, {'text': 'TET', 'type': 'Chemical', 'start': 1082, 'end': 1085, 'mesh': 'C009438'}, {'text': 'FAN', 'type': 'Chemical', 'start': 1090, 'end': 1093, 'mesh': 'C060802'}]"
+53,10526274,Gemcitabine plus vinorelbine in nonsmall cell lung carcinoma patients age 70 years or older or patients who cannot receive cisplatin. Oncopaz Cooperative Group.,"BACKGROUND: Although the prevalence of nonsmall cell lung carcinoma (NSCLC) is high among elderly patients, few data are available regarding the efficacy and toxicity of chemotherapy in this group of patients. Recent reports indicate that single agent therapy with vinorelbine (VNB) or gemcitabine (GEM) may obtain a response rate of 20-30% in elderly patients, with acceptable toxicity and improvement in symptoms and quality of life. In the current study the efficacy and toxicity of the combination of GEM and VNB in elderly patients with advanced NSCLC or those with some contraindication to receiving cisplatin were assessed. METHODS: Forty-nine patients with advanced NSCLC were included, 38 of whom were age >/= 70 years and 11 were age < 70 years but who had some contraindication to receiving cisplatin. All patients were evaluable for response and toxicity. Treatment was comprised of VNB, 25 mg/m(2), plus GEM, 1000 mg/m(2), both on Days 1, 8, and 15 every 28 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: One hundred sixty-five courses were administered, with a median of 3. 6 courses per patient. The overall response rate was 26% (95% confidence interval, 15-41%). Two patients attained a complete response (4%) and 11 patients (22%) achieved a partial response. Eastern Cooperative Oncology Group performance status improved in 35% of those patients with an initial value > 0, whereas relief of at least 1 symptom without worsening of other symptoms was noted in 27 patients (55%). The median time to progression was 16 weeks and the 1-year survival rate was 33%. Toxicity was mild. Six patients (12%) had World Health Organization Grade 3-4 neutropenia, 2 patients (4%) had Grade 3-4 thrombocytopenia, and 2 patients (4%) had Grade 3 neurotoxicity. Three patients with severe neutropenia (6%) died of sepsis. The median age of those patients developing Grade 3-4 neutropenia was significantly higher than that of the remaining patients (75 years vs. 72 years; P = 0.047). CONCLUSIONS: The combination of GEM and VNB is moderately active and well tolerated except in patients age >/= 75 years. This age group had an increased risk of myelosuppression. Therefore the prophylactic use of granulocyte-colony stimulating factor should be considered with this treatment. New chemotherapy combinations with higher activity and lower toxicity are needed for elderly patients with advanced NSCLC.","[{'text': 'Gemcitabine', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'C056507'}, {'text': 'vinorelbine', 'type': 'Chemical', 'start': 17, 'end': 28, 'mesh': 'C030852'}, {'text': 'nonsmall cell lung carcinoma', 'type': 'Disease', 'start': 32, 'end': 60, 'mesh': 'D002289'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 123, 'end': 132, 'mesh': 'D002945'}, {'text': 'nonsmall cell lung carcinoma', 'type': 'Disease', 'start': 200, 'end': 228, 'mesh': 'D002289'}, {'text': 'NSCLC', 'type': 'Disease', 'start': 230, 'end': 235, 'mesh': 'D002289'}, {'text': 'toxicity', 'type': 'Disease', 'start': 319, 'end': 327, 'mesh': 'D064420'}, {'text': 'vinorelbine', 'type': 'Chemical', 'start': 426, 'end': 437, 'mesh': 'C030852'}, {'text': 'VNB', 'type': 'Chemical', 'start': 439, 'end': 442, 'mesh': 'C030852'}, {'text': 'gemcitabine', 'type': 'Chemical', 'start': 447, 'end': 458, 'mesh': 'C056507'}, {'text': 'GEM', 'type': 'Chemical', 'start': 460, 'end': 463, 'mesh': 'C056507'}, {'text': 'toxicity', 'type': 'Disease', 'start': 539, 'end': 547, 'mesh': 'D064420'}, {'text': 'toxicity', 'type': 'Disease', 'start': 635, 'end': 643, 'mesh': 'D064420'}, {'text': 'GEM', 'type': 'Chemical', 'start': 666, 'end': 669, 'mesh': 'C056507'}, {'text': 'VNB', 'type': 'Chemical', 'start': 674, 'end': 677, 'mesh': 'C030852'}, {'text': 'NSCLC', 'type': 'Disease', 'start': 712, 'end': 717, 'mesh': 'D002289'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 767, 'end': 776, 'mesh': 'D002945'}, {'text': 'NSCLC', 'type': 'Disease', 'start': 835, 'end': 840, 'mesh': 'D002289'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 963, 'end': 972, 'mesh': 'D002945'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1019, 'end': 1027, 'mesh': 'D064420'}, {'text': 'VNB', 'type': 'Chemical', 'start': 1056, 'end': 1059, 'mesh': 'C030852'}, {'text': 'GEM', 'type': 'Chemical', 'start': 1078, 'end': 1081, 'mesh': 'C056507'}, {'text': 'Toxicity', 'type': 'Disease', 'start': 1795, 'end': 1803, 'mesh': 'D064420'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 1873, 'end': 1884, 'mesh': 'D009503'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 1916, 'end': 1932, 'mesh': 'D013921'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 1966, 'end': 1979, 'mesh': 'D020258'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 2008, 'end': 2019, 'mesh': 'D009503'}, {'text': 'sepsis', 'type': 'Disease', 'start': 2033, 'end': 2039, 'mesh': 'D018805'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 2095, 'end': 2106, 'mesh': 'D009503'}, {'text': 'GEM', 'type': 'Chemical', 'start': 2236, 'end': 2239, 'mesh': 'C056507'}, {'text': 'VNB', 'type': 'Chemical', 'start': 2244, 'end': 2247, 'mesh': 'C030852'}, {'text': 'myelosuppression', 'type': 'Disease', 'start': 2365, 'end': 2381, 'mesh': 'D001855'}, {'text': 'toxicity', 'type': 'Disease', 'start': 2558, 'end': 2566, 'mesh': 'D064420'}, {'text': 'NSCLC', 'type': 'Disease', 'start': 2613, 'end': 2618, 'mesh': 'D002289'}]"
+54,10669626,Warfarin-induced artery calcification is accelerated by growth and vitamin D.,"The present studies demonstrate that growth and vitamin D treatment enhance the extent of artery calcification in rats given sufficient doses of Warfarin to inhibit gamma-carboxylation of matrix Gla protein, a calcification inhibitor known to be expressed by smooth muscle cells and macrophages in the artery wall. The first series of experiments examined the influence of age and growth status on artery calcification in Warfarin-treated rats. Treatment for 2 weeks with Warfarin caused massive focal calcification of the artery media in 20-day-old rats and less extensive focal calcification in 42-day-old rats. In contrast, no artery calcification could be detected in 10-month-old adult rats even after 4 weeks of Warfarin treatment. To directly examine the importance of growth to Warfarin-induced artery calcification in animals of the same age, 20-day-old rats were fed for 2 weeks either an ad libitum diet or a 6-g/d restricted diet that maintains weight but prevents growth. Concurrent treatment of both dietary groups with Warfarin produced massive focal calcification of the artery media in the ad libitum-fed rats but no detectable artery calcification in the restricted-diet, growth-inhibited group. Although the explanation for the association between artery calcification and growth status cannot be determined from the present study, there was a relationship between higher serum phosphate and susceptibility to artery calcification, with 30% higher levels of serum phosphate in young, ad libitum-fed rats compared with either of the groups that was resistant to Warfarin-induced artery calcification, ie, the 10-month-old rats and the restricted-diet, growth-inhibited young rats. This observation suggests that increased susceptibility to Warfarin-induced artery calcification could be related to higher serum phosphate levels. The second set of experiments examined the possible synergy between vitamin D and Warfarin in artery calcification. High doses of vitamin D are known to cause calcification of the artery media in as little as 3 to 4 days. High doses of the vitamin K antagonist Warfarin are also known to cause calcification of the artery media, but at treatment times of 2 weeks or longer yet not at 1 week. In the current study, we investigated the synergy between these 2 treatments and found that concurrent Warfarin administration dramatically increased the extent of calcification in the media of vitamin D-treated rats at 3 and 4 days. There was a close parallel between the effect of vitamin D dose on artery calcification and the effect of vitamin D dose on the elevation of serum calcium, which suggests that vitamin D may induce artery calcification through its effect on serum calcium. Because Warfarin treatment had no effect on the elevation in serum calcium produced by vitamin D, the synergy between Warfarin and vitamin D is probably best explained by the hypothesis that Warfarin inhibits the activity of matrix Gla protein as a calcification inhibitor. High levels of matrix Gla protein are found at sites of artery calcification in rats treated with vitamin D plus Warfarin, and chemical analysis showed that the protein that accumulated was indeed not gamma-carboxylated. These observations indicate that although the gamma-carboxyglutamate residues of matrix Gla protein are apparently required for its function as a calcification inhibitor, they are not required for its accumulation at calcification sites.","[{'text': 'Warfarin', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D014859'}, {'text': 'artery calcification', 'type': 'Disease', 'start': 17, 'end': 37, 'mesh': 'D061205'}, {'text': 'vitamin D', 'type': 'Chemical', 'start': 67, 'end': 76, 'mesh': 'D014807'}, {'text': 'vitamin D', 'type': 'Chemical', 'start': 126, 'end': 135, 'mesh': 'D014807'}, {'text': 'artery calcification', 'type': 'Disease', 'start': 168, 'end': 188, 'mesh': 'D061205'}, {'text': 'Warfarin', 'type': 'Chemical', 'start': 223, 'end': 231, 'mesh': 'D014859'}, {'text': 'calcification', 'type': 'Disease', 'start': 288, 'end': 301, 'mesh': 'D002114'}, {'text': 'artery calcification', 'type': 'Disease', 'start': 476, 'end': 496, 'mesh': 'D061205'}, {'text': 'Warfarin', 'type': 'Chemical', 'start': 500, 'end': 508, 'mesh': 'D014859'}, {'text': 'Warfarin', 'type': 'Chemical', 'start': 550, 'end': 558, 'mesh': 'D014859'}, {'text': 'calcification of the artery', 'type': 'Disease', 'start': 580, 'end': 607, 'mesh': 'D061205'}, {'text': 'calcification', 'type': 'Disease', 'start': 658, 'end': 671, 'mesh': 'D002114'}, {'text': 'artery calcification', 'type': 'Disease', 'start': 708, 'end': 728, 'mesh': 'D061205'}, {'text': 'Warfarin', 'type': 'Chemical', 'start': 796, 'end': 804, 'mesh': 'D014859'}, {'text': 'Warfarin', 'type': 'Chemical', 'start': 864, 'end': 872, 'mesh': 'D014859'}, {'text': 'artery calcification', 'type': 'Disease', 'start': 881, 'end': 901, 'mesh': 'D061205'}, {'text': 'Warfarin', 'type': 'Chemical', 'start': 1112, 'end': 1120, 'mesh': 'D014859'}, {'text': 'calcification of the artery', 'type': 'Disease', 'start': 1144, 'end': 1171, 'mesh': 'D061205'}, {'text': 'artery calcification', 'type': 'Disease', 'start': 1223, 'end': 1243, 'mesh': 'D061205'}, {'text': 'artery calcification', 'type': 'Disease', 'start': 1345, 'end': 1365, 'mesh': 'D061205'}, {'text': 'phosphate', 'type': 'Chemical', 'start': 1475, 'end': 1484, 'mesh': 'D010710'}, {'text': 'artery calcification', 'type': 'Disease', 'start': 1507, 'end': 1527, 'mesh': 'D061205'}, {'text': 'phosphate', 'type': 'Chemical', 'start': 1561, 'end': 1570, 'mesh': 'D010710'}, {'text': 'Warfarin', 'type': 'Chemical', 'start': 1658, 'end': 1666, 'mesh': 'D014859'}, {'text': 'artery calcification', 'type': 'Disease', 'start': 1675, 'end': 1695, 'mesh': 'D061205'}, {'text': 'Warfarin', 'type': 'Chemical', 'start': 1836, 'end': 1844, 'mesh': 'D014859'}, {'text': 'artery calcification', 'type': 'Disease', 'start': 1853, 'end': 1873, 'mesh': 'D061205'}, {'text': 'phosphate', 'type': 'Chemical', 'start': 1907, 'end': 1916, 'mesh': 'D010710'}, {'text': 'vitamin D', 'type': 'Chemical', 'start': 1993, 'end': 2002, 'mesh': 'D014807'}, {'text': 'Warfarin', 'type': 'Chemical', 'start': 2007, 'end': 2015, 'mesh': 'D014859'}, {'text': 'artery calcification', 'type': 'Disease', 'start': 2019, 'end': 2039, 'mesh': 'D061205'}, {'text': 'vitamin D', 'type': 'Chemical', 'start': 2055, 'end': 2064, 'mesh': 'D014807'}, {'text': 'calcification of the artery', 'type': 'Disease', 'start': 2084, 'end': 2111, 'mesh': 'D061205'}, {'text': 'vitamin K', 'type': 'Chemical', 'start': 2165, 'end': 2174, 'mesh': 'D014812'}, {'text': 'Warfarin', 'type': 'Chemical', 'start': 2186, 'end': 2194, 'mesh': 'D014859'}, {'text': 'calcification of the artery', 'type': 'Disease', 'start': 2219, 'end': 2246, 'mesh': 'D061205'}, {'text': 'Warfarin', 'type': 'Chemical', 'start': 2420, 'end': 2428, 'mesh': 'D014859'}, {'text': 'calcification', 'type': 'Disease', 'start': 2481, 'end': 2494, 'mesh': 'D002114'}, {'text': 'vitamin D', 'type': 'Chemical', 'start': 2511, 'end': 2520, 'mesh': 'D014807'}, {'text': 'vitamin D', 'type': 'Chemical', 'start': 2600, 'end': 2609, 'mesh': 'D014807'}, {'text': 'artery calcification', 'type': 'Disease', 'start': 2618, 'end': 2638, 'mesh': 'D061205'}, {'text': 'vitamin D', 'type': 'Chemical', 'start': 2657, 'end': 2666, 'mesh': 'D014807'}, {'text': 'calcium', 'type': 'Chemical', 'start': 2698, 'end': 2705, 'mesh': 'D002118'}, {'text': 'vitamin D', 'type': 'Chemical', 'start': 2727, 'end': 2736, 'mesh': 'D014807'}, {'text': 'artery calcification', 'type': 'Disease', 'start': 2748, 'end': 2768, 'mesh': 'D061205'}, {'text': 'calcium', 'type': 'Chemical', 'start': 2797, 'end': 2804, 'mesh': 'D002118'}, {'text': 'Warfarin', 'type': 'Chemical', 'start': 2814, 'end': 2822, 'mesh': 'D014859'}, {'text': 'calcium', 'type': 'Chemical', 'start': 2873, 'end': 2880, 'mesh': 'D002118'}, {'text': 'vitamin D', 'type': 'Chemical', 'start': 2893, 'end': 2902, 'mesh': 'D014807'}, {'text': 'Warfarin', 'type': 'Chemical', 'start': 2924, 'end': 2932, 'mesh': 'D014859'}, {'text': 'vitamin D', 'type': 'Chemical', 'start': 2937, 'end': 2946, 'mesh': 'D014807'}, {'text': 'Warfarin', 'type': 'Chemical', 'start': 2997, 'end': 3005, 'mesh': 'D014859'}, {'text': 'calcification', 'type': 'Disease', 'start': 3055, 'end': 3068, 'mesh': 'D002114'}, {'text': 'artery calcification', 'type': 'Disease', 'start': 3136, 'end': 3156, 'mesh': 'D061205'}, {'text': 'vitamin D', 'type': 'Chemical', 'start': 3178, 'end': 3187, 'mesh': 'D014807'}, {'text': 'Warfarin', 'type': 'Chemical', 'start': 3193, 'end': 3201, 'mesh': 'D014859'}, {'text': 'gamma-carboxylated', 'type': 'Chemical', 'start': 3281, 'end': 3299, 'mesh': 'D015055'}, {'text': 'gamma-carboxyglutamate', 'type': 'Chemical', 'start': 3347, 'end': 3369, 'mesh': 'D015055'}, {'text': 'calcification', 'type': 'Disease', 'start': 3447, 'end': 3460, 'mesh': 'D002114'}, {'text': 'calcification', 'type': 'Disease', 'start': 3518, 'end': 3531, 'mesh': 'D002114'}]"
+55,11379838,Antidepressant-induced mania in bipolar patients: identification of risk factors.,"BACKGROUND: Concerns about possible risks of switching to mania associated with antidepressants continue to interfere with the establishment of an optimal treatment paradigm for bipolar depression. METHOD: The response of 44 patients meeting DSM-IV criteria for bipolar disorder to naturalistic treatment was assessed for at least 6 weeks using the Montgomery-Asberg Depression Rating Scale and the Bech-Rafaelson Mania Rating Scale. Patients who experienced a manic or hypomanic switch were compared with those who did not on several variables including age, sex, diagnosis (DSM-IV bipolar I vs. bipolar II), number of previous manic episodes, type of antidepressant therapy used (electroconvulsive therapy vs. antidepressant drugs and, more particularly, selective serotonin reuptake inhibitors [SSRIs]), use and type of mood stabilizers (lithium vs. anticonvulsants), and temperament of the patient, assessed during a normothymic period using the hyperthymia component of the Semi-structured Affective Temperament Interview. RESULTS: Switches to hypomania or mania occurred in 27% of all patients (N = 12) (and in 24% of the subgroup of patients treated with SSRIs [8/33]); 16% (N = 7) experienced manic episodes, and 11% (N = 5) experienced hypomanic episodes. Sex, age, diagnosis (bipolar I vs. bipolar II), and additional treatment did not affect the risk of switching. The incidence of mood switches seemed not to differ between patients receiving an anticonvulsant and those receiving no mood stabilizer. In contrast, mood switches were less frequent in patients receiving lithium (15%, 4/26) than in patients not treated with lithium (44%, 8/18; p = .04). The number of previous manic episodes did not affect the probability of switching, whereas a high score on the hyperthymia component of the Semistructured Affective Temperament Interview was associated with a greater risk of switching (p = .008). CONCLUSION: The frequency of mood switching associated with acute antidepressant therapy may be reduced by lithium treatment. Particular attention should be paid to patients with a hyperthymic temperament, who have a greater risk of mood switches.","[{'text': 'Antidepressant', 'type': 'Chemical', 'start': 0, 'end': 14, 'mesh': 'D000928'}, {'text': 'mania', 'type': 'Disease', 'start': 23, 'end': 28, 'mesh': 'D001714'}, {'text': 'bipolar', 'type': 'Disease', 'start': 32, 'end': 39, 'mesh': 'D001714'}, {'text': 'mania', 'type': 'Disease', 'start': 140, 'end': 145, 'mesh': 'D001714'}, {'text': 'antidepressants', 'type': 'Chemical', 'start': 162, 'end': 177, 'mesh': 'D000928'}, {'text': 'bipolar depression', 'type': 'Disease', 'start': 260, 'end': 278, 'mesh': 'D001714'}, {'text': 'bipolar disorder', 'type': 'Disease', 'start': 344, 'end': 360, 'mesh': 'D001714'}, {'text': 'manic', 'type': 'Disease', 'start': 543, 'end': 548, 'mesh': 'D001714'}, {'text': 'hypomanic', 'type': 'Disease', 'start': 552, 'end': 561, 'mesh': 'D001714'}, {'text': 'DSM-IV bipolar I', 'type': 'Disease', 'start': 658, 'end': 674, 'mesh': 'D001714'}, {'text': 'bipolar II', 'type': 'Disease', 'start': 679, 'end': 689, 'mesh': 'D001714'}, {'text': 'manic', 'type': 'Disease', 'start': 711, 'end': 716, 'mesh': 'D001714'}, {'text': 'antidepressant', 'type': 'Chemical', 'start': 735, 'end': 749, 'mesh': 'D000928'}, {'text': 'antidepressant', 'type': 'Chemical', 'start': 794, 'end': 808, 'mesh': 'D000928'}, {'text': 'serotonin reuptake inhibitors', 'type': 'Chemical', 'start': 849, 'end': 878, 'mesh': 'D017367'}, {'text': 'SSRIs', 'type': 'Chemical', 'start': 880, 'end': 885, 'mesh': 'D017367'}, {'text': 'lithium', 'type': 'Chemical', 'start': 923, 'end': 930, 'mesh': 'D008094'}, {'text': 'hypomania', 'type': 'Disease', 'start': 1131, 'end': 1140, 'mesh': 'D001714'}, {'text': 'mania', 'type': 'Disease', 'start': 1144, 'end': 1149, 'mesh': 'D001714'}, {'text': 'SSRIs', 'type': 'Chemical', 'start': 1244, 'end': 1249, 'mesh': 'D017367'}, {'text': 'manic', 'type': 'Disease', 'start': 1283, 'end': 1288, 'mesh': 'D001714'}, {'text': 'hypomanic', 'type': 'Disease', 'start': 1327, 'end': 1336, 'mesh': 'D001714'}, {'text': 'bipolar I', 'type': 'Disease', 'start': 1368, 'end': 1377, 'mesh': 'D001714'}, {'text': 'bipolar II', 'type': 'Disease', 'start': 1382, 'end': 1392, 'mesh': 'D001714'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1663, 'end': 1670, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1717, 'end': 1724, 'mesh': 'D008094'}, {'text': 'manic', 'type': 'Disease', 'start': 1770, 'end': 1775, 'mesh': 'D001714'}, {'text': 'antidepressant', 'type': 'Chemical', 'start': 2060, 'end': 2074, 'mesh': 'D000928'}, {'text': 'lithium', 'type': 'Chemical', 'start': 2101, 'end': 2108, 'mesh': 'D008094'}]"
+56,11419773,Caffeine-induced cardiac arrhythmia: an unrecognised danger of healthfood products.,"We describe a 25-year-old woman with pre-existing mitral valve prolapse who developed intractable ventricular fibrillation after consuming a ""natural energy"" guarana health drink containing a high concentration of caffeine. This case highlights the need for adequate labelling and regulation of such products.","[{'text': 'Caffeine', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D002110'}, {'text': 'cardiac arrhythmia', 'type': 'Disease', 'start': 17, 'end': 35, 'mesh': 'D001145'}, {'text': 'mitral valve prolapse', 'type': 'Disease', 'start': 134, 'end': 155, 'mesh': 'D008945'}, {'text': 'ventricular fibrillation', 'type': 'Disease', 'start': 182, 'end': 206, 'mesh': 'D014693'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 298, 'end': 306, 'mesh': 'D002110'}]"
+57,11581460,Bladder retention of urine as a result of continuous intravenous infusion of fentanyl: 2 case reports.,"Sedation has been commonly used in the neonate to decrease the stress and pain from the noxious stimuli and invasive procedures in the neonatal intensive care unit, as well as to facilitate synchrony between ventilator and spontaneous breaths. Fentanyl, an opioid analgesic, is frequently used in the neonatal intensive care unit setting for these very purposes. Various reported side effects of fentanyl administration include chest wall rigidity, hypotension, respiratory depression, and bradycardia. Here, 2 cases of urinary bladder retention leading to renal pelvocalyceal dilatation mimicking hydronephrosis as a result of continuous infusion of fentanyl are reported.","[{'text': 'retention of urine', 'type': 'Disease', 'start': 8, 'end': 26, 'mesh': 'D016055'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 77, 'end': 85, 'mesh': 'D005283'}, {'text': 'pain', 'type': 'Disease', 'start': 177, 'end': 181, 'mesh': 'D010146'}, {'text': 'Fentanyl', 'type': 'Chemical', 'start': 347, 'end': 355, 'mesh': 'D005283'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 499, 'end': 507, 'mesh': 'D005283'}, {'text': 'chest wall rigidity', 'type': 'Disease', 'start': 531, 'end': 550, 'mesh': 'D009127'}, {'text': 'hypotension', 'type': 'Disease', 'start': 552, 'end': 563, 'mesh': 'D007022'}, {'text': 'respiratory depression', 'type': 'Disease', 'start': 565, 'end': 587, 'mesh': 'D012131'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 593, 'end': 604, 'mesh': 'D001919'}, {'text': 'urinary bladder retention', 'type': 'Disease', 'start': 623, 'end': 648, 'mesh': 'D001745'}, {'text': 'hydronephrosis', 'type': 'Disease', 'start': 701, 'end': 715, 'mesh': 'D006869'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 754, 'end': 762, 'mesh': 'D005283'}]"
+58,11706060,Combined antiretroviral therapy causes cardiomyopathy and elevates plasma lactate in transgenic AIDS mice.,"Highly active antiretroviral therapy (HAART) is implicated in cardiomyopathy (CM) and in elevated plasma lactate (LA) in AIDS through mechanisms of mitochondrial dysfunction. To determine mitochondrial events from HAART in vivo, 8-week-old hemizygous transgenic AIDS mice (NL4-3Delta gag/pol; TG) and wild-type FVB/n littermates were treated with the HAART combination of zidovudine, lamivudine, and indinavir or vehicle control for 10 days or 35 days. At termination of the experiments, mice underwent echocardiography, quantitation of abundance of molecular markers of CM (ventricular mRNA encoding atrial natriuretic factor [ANF] and sarcoplasmic calcium ATPase [SERCA2]), and determination of plasma LA. Myocardial histologic features were analyzed semiquantitatively and results were confirmed by transmission electron microscopy. After 35 days in the TG + HAART cohort, left ventricular mass increased 160% by echocardiography. Molecularly, ANF mRNA increased 250% and SERCA2 mRNA decreased 57%. Biochemically, LA was elevated (8.5 +/- 2.0 mM). Pathologically, granular cytoplasmic changes were found in cardiac myocytes, indicating enlarged, damaged mitochondria. Findings were confirmed ultrastructurally. No changes were found in other cohorts. After 10 days, only ANF was elevated, and only in the TG + HAART cohort. Results show that cumulative HAART caused mitochondrial CM with elevated LA in AIDS transgenic mice.","[{'text': 'cardiomyopathy', 'type': 'Disease', 'start': 39, 'end': 53, 'mesh': 'D009202'}, {'text': 'lactate', 'type': 'Chemical', 'start': 74, 'end': 81, 'mesh': 'D019344'}, {'text': 'AIDS', 'type': 'Disease', 'start': 96, 'end': 100, 'mesh': 'D000163'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 169, 'end': 183, 'mesh': 'D009202'}, {'text': 'CM', 'type': 'Disease', 'start': 185, 'end': 187, 'mesh': 'D009202'}, {'text': 'lactate', 'type': 'Chemical', 'start': 212, 'end': 219, 'mesh': 'D019344'}, {'text': 'LA', 'type': 'Chemical', 'start': 221, 'end': 223, 'mesh': 'D019344'}, {'text': 'AIDS', 'type': 'Disease', 'start': 228, 'end': 232, 'mesh': 'D000163'}, {'text': 'mitochondrial dysfunction', 'type': 'Disease', 'start': 255, 'end': 280, 'mesh': 'D028361'}, {'text': 'AIDS', 'type': 'Disease', 'start': 369, 'end': 373, 'mesh': 'D000163'}, {'text': 'zidovudine', 'type': 'Chemical', 'start': 479, 'end': 489, 'mesh': 'D015215'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 491, 'end': 501, 'mesh': 'D019259'}, {'text': 'indinavir', 'type': 'Chemical', 'start': 507, 'end': 516, 'mesh': 'D019469'}, {'text': 'CM', 'type': 'Disease', 'start': 678, 'end': 680, 'mesh': 'D009202'}, {'text': 'calcium', 'type': 'Chemical', 'start': 757, 'end': 764, 'mesh': 'D002118'}, {'text': 'LA', 'type': 'Chemical', 'start': 811, 'end': 813, 'mesh': 'D019344'}, {'text': 'LA', 'type': 'Chemical', 'start': 1124, 'end': 1126, 'mesh': 'D019344'}, {'text': 'CM', 'type': 'Disease', 'start': 1490, 'end': 1492, 'mesh': 'D009202'}, {'text': 'LA', 'type': 'Chemical', 'start': 1507, 'end': 1509, 'mesh': 'D019344'}, {'text': 'AIDS', 'type': 'Disease', 'start': 1513, 'end': 1517, 'mesh': 'D000163'}]"
+59,11752354,Oral contraceptives and the risk of myocardial infarction.,"BACKGROUND: An association between the use of oral contraceptives and the risk of myocardial infarction has been found in some, but not all, studies. We investigated this association, according to the type of progestagen included in third-generation (i.e., desogestrel or gestodene) and second-generation (i.e., levonorgestrel) oral contraceptives, the dose of estrogen, and the presence or absence of prothrombotic mutations METHODS: In a nationwide, population-based, case-control study, we identified and enrolled 248 women 18 through 49 years of age who had had a first myocardial infarction between 1990 and 1995 and 925 control women who had not had a myocardial infarction and who were matched for age, calendar year of the index event, and area of residence. Subjects supplied information on oral-contraceptive use and major cardiovascular risk factors. An analysis for factor V Leiden and the G20210A mutation in the prothrombin gene was conducted in 217 patients and 763 controls RESULTS: The odds ratio for myocardial infarction among women who used any type of combined oral contraceptive, as compared with nonusers, was 2.0 (95 percent confidence interval, 1.5 to 2.8). The adjusted odds ratio was 2.5 (95 percent confidence interval, 1.5 to 4.1) among women who used second-generation oral contraceptives and 1.3 (95 percent confidence interval, 0.7 to 2.5) among those who used third-generation oral contraceptives. Among women who used oral contraceptives, the odds ratio was 2.1 (95 percent confidence interval, 1.5 to 3.0) for those without a prothrombotic mutation and 1.9 (95 percent confidence interval, 0.6 to 5.5) for those with a mutation CONCLUSIONS: The risk of myocardial infarction was increased among women who used second-generation oral contraceptives. The results with respect to the use of third-generation oral contraceptives were inconclusive but suggested that the risk was lower than the risk associated with second-generation oral contraceptives. The risk of myocardial infarction was similar among women who used oral contraceptives whether or not they had a prothrombotic mutation.","[{'text': 'Oral contraceptives', 'type': 'Chemical', 'start': 0, 'end': 19, 'mesh': 'D003276'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 36, 'end': 57, 'mesh': 'D009203'}, {'text': 'oral contraceptives', 'type': 'Chemical', 'start': 105, 'end': 124, 'mesh': 'D003276'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 141, 'end': 162, 'mesh': 'D009203'}, {'text': 'progestagen', 'type': 'Chemical', 'start': 268, 'end': 279, 'mesh': 'D011372'}, {'text': 'desogestrel', 'type': 'Chemical', 'start': 316, 'end': 327, 'mesh': 'D017135'}, {'text': 'gestodene', 'type': 'Chemical', 'start': 331, 'end': 340, 'mesh': 'C033273'}, {'text': 'levonorgestrel', 'type': 'Chemical', 'start': 371, 'end': 385, 'mesh': 'D016912'}, {'text': 'oral contraceptives', 'type': 'Chemical', 'start': 387, 'end': 406, 'mesh': 'D003276'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 420, 'end': 428, 'mesh': 'D004967'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 633, 'end': 654, 'mesh': 'D009203'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 717, 'end': 738, 'mesh': 'D009203'}, {'text': 'oral-contraceptive', 'type': 'Chemical', 'start': 859, 'end': 877, 'mesh': 'D003276'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 1077, 'end': 1098, 'mesh': 'D009203'}, {'text': 'oral contraceptive', 'type': 'Chemical', 'start': 1141, 'end': 1159, 'mesh': 'D003276'}, {'text': 'oral contraceptives', 'type': 'Chemical', 'start': 1358, 'end': 1377, 'mesh': 'D003276'}, {'text': 'oral contraceptives', 'type': 'Chemical', 'start': 1469, 'end': 1488, 'mesh': 'D003276'}, {'text': 'oral contraceptives', 'type': 'Chemical', 'start': 1511, 'end': 1530, 'mesh': 'D003276'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 1747, 'end': 1768, 'mesh': 'D009203'}, {'text': 'oral contraceptives', 'type': 'Chemical', 'start': 1822, 'end': 1841, 'mesh': 'D003276'}, {'text': 'oral contraceptives', 'type': 'Chemical', 'start': 1899, 'end': 1918, 'mesh': 'D003276'}, {'text': 'oral contraceptives', 'type': 'Chemical', 'start': 2023, 'end': 2042, 'mesh': 'D003276'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 2056, 'end': 2077, 'mesh': 'D009203'}, {'text': 'oral contraceptives', 'type': 'Chemical', 'start': 2111, 'end': 2130, 'mesh': 'D003276'}]"
+60,12369736,Effects of 5-HT1B receptor ligands microinjected into the accumbal shell or core on the cocaine-induced locomotor hyperactivity in rats.,"The present study was designed to examine the effect of 5-HT1B receptor ligands microinjected into the subregions of the nucleus accumbens (the shell and the core) on the locomotor hyperactivity induced by cocaine in rats. Male Wistar rats were implanted bilaterally with cannulae into the accumbens shell or core, and then were locally injected with GR 55562 (an antagonist of 5-HT1B receptors) or CP 93129 (an agonist of 5-HT1B receptors). Given alone to any accumbal subregion, GR 55562 (0.1-10 microg/side) or CP 93129 (0.1-10 microg/side) did not change basal locomotor activity. Systemic cocaine (10 mg/kg) significantly increased the locomotor activity of rats. GR 55562 (0.1-10 microg/side), administered intra-accumbens shell prior to cocaine, dose-dependently attenuated the psychostimulant-induced locomotor hyperactivity. Such attenuation was not found in animals which had been injected with GR 55562 into the accumbens core. When injected into the accumbens shell (but not the core) before cocaine, CP 93129 (0.1-10 microg/side) enhanced the locomotor response to cocaine; the maximum effect being observed after 10 microg/side of the agonist. The later enhancement was attenuated after intra-accumbens shell treatment with GR 55562 (1 microg/side). Our findings indicate that cocaine induced hyperlocomotion is modified by 5-HT1B receptor ligands microinjected into the accumbens shell, but not core, this modification consisting in inhibitory and facilitatory effects of the 5-HT1B receptor antagonist (GR 55562) and agonist (CP 93129), respectively. In other words, the present results suggest that the accumbal shell 5-HT1B receptors play a permissive role in the behavioural response to the psychostimulant.","[{'text': 'cocaine', 'type': 'Chemical', 'start': 88, 'end': 95, 'mesh': 'D003042'}, {'text': 'locomotor hyperactivity', 'type': 'Disease', 'start': 104, 'end': 127, 'mesh': 'D009069'}, {'text': 'locomotor hyperactivity', 'type': 'Disease', 'start': 308, 'end': 331, 'mesh': 'D009069'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 343, 'end': 350, 'mesh': 'D003042'}, {'text': 'GR 55562', 'type': 'Chemical', 'start': 488, 'end': 496, 'mesh': 'C103477'}, {'text': 'CP 93129', 'type': 'Chemical', 'start': 536, 'end': 544, 'mesh': 'C065046'}, {'text': 'GR 55562', 'type': 'Chemical', 'start': 618, 'end': 626, 'mesh': 'C103477'}, {'text': 'CP 93129', 'type': 'Chemical', 'start': 651, 'end': 659, 'mesh': 'C065046'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 731, 'end': 738, 'mesh': 'D003042'}, {'text': 'GR 55562', 'type': 'Chemical', 'start': 806, 'end': 814, 'mesh': 'C103477'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 881, 'end': 888, 'mesh': 'D003042'}, {'text': 'locomotor hyperactivity', 'type': 'Disease', 'start': 946, 'end': 969, 'mesh': 'D009069'}, {'text': 'GR 55562', 'type': 'Chemical', 'start': 1042, 'end': 1050, 'mesh': 'C103477'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1141, 'end': 1148, 'mesh': 'D003042'}, {'text': 'CP 93129', 'type': 'Chemical', 'start': 1150, 'end': 1158, 'mesh': 'C065046'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1215, 'end': 1222, 'mesh': 'D003042'}, {'text': 'GR 55562', 'type': 'Chemical', 'start': 1375, 'end': 1383, 'mesh': 'C103477'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1428, 'end': 1435, 'mesh': 'D003042'}, {'text': 'hyperlocomotion', 'type': 'Disease', 'start': 1444, 'end': 1459, 'mesh': 'D009069'}, {'text': 'GR 55562', 'type': 'Chemical', 'start': 1656, 'end': 1664, 'mesh': 'C103477'}, {'text': 'CP 93129', 'type': 'Chemical', 'start': 1679, 'end': 1687, 'mesh': 'C065046'}]"
+61,12639165,Ticlopidine-induced cholestatic hepatitis.,"OBJECTIVE: To report 2 cases of ticlopidine-induced cholestatic hepatitis, investigate its mechanism, and compare the observed main characteristics with those of the published cases. CASE SUMMARIES: Two patients developed prolonged cholestatic hepatitis after receiving ticlopidine following percutaneous coronary angioplasty, with complete remission during the follow-up period. T-cell stimulation by therapeutic concentration of ticlopidine was demonstrated in vitro in the patients, but not in healthy controls. DISCUSSION: Cholestatic hepatitis is a rare complication of the antiplatelet agent ticlopidine; several cases have been reported but few in the English literature. Our patients developed jaundice following treatment with ticlopidine and showed the clinical and laboratory characteristics of cholestatic hepatitis, which resolved after discontinuation of the drug. Hepatitis may develop weeks after discontinuation of the drug and may run a prolonged course, but complete remission was observed in all reported cases. An objective causality assessment revealed that the adverse drug event was probably related to the use of ticlopidine. The mechanisms of this ticlopidine-induced cholestasis are unclear. Immune mechanisms may be involved in the drug's hepatotoxicity, as suggested by the T-cell stimulation study reported here. CONCLUSIONS: Cholestatic hepatitis is a rare adverse effect of ticlopidine that may be immune mediated. Patients receiving the drug should be monitored with liver function tests along with complete blood cell counts. This complication will be observed even less often in the future as ticlopidine is being replaced by the newer antiplatelet agent clopidogrel.","[{'text': 'Ticlopidine', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D013988'}, {'text': 'ticlopidine', 'type': 'Chemical', 'start': 75, 'end': 86, 'mesh': 'D013988'}, {'text': 'ticlopidine', 'type': 'Chemical', 'start': 313, 'end': 324, 'mesh': 'D013988'}, {'text': 'ticlopidine', 'type': 'Chemical', 'start': 474, 'end': 485, 'mesh': 'D013988'}, {'text': 'ticlopidine', 'type': 'Chemical', 'start': 641, 'end': 652, 'mesh': 'D013988'}, {'text': 'jaundice', 'type': 'Disease', 'start': 745, 'end': 753, 'mesh': 'D007565'}, {'text': 'ticlopidine', 'type': 'Chemical', 'start': 779, 'end': 790, 'mesh': 'D013988'}, {'text': 'Hepatitis', 'type': 'Disease', 'start': 922, 'end': 931, 'mesh': 'D056486'}, {'text': 'ticlopidine', 'type': 'Chemical', 'start': 1181, 'end': 1192, 'mesh': 'D013988'}, {'text': 'ticlopidine', 'type': 'Chemical', 'start': 1217, 'end': 1228, 'mesh': 'D013988'}, {'text': 'cholestasis', 'type': 'Disease', 'start': 1237, 'end': 1248, 'mesh': 'D002779'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 1310, 'end': 1324, 'mesh': 'D056486'}, {'text': 'ticlopidine', 'type': 'Chemical', 'start': 1449, 'end': 1460, 'mesh': 'D013988'}, {'text': 'ticlopidine', 'type': 'Chemical', 'start': 1671, 'end': 1682, 'mesh': 'D013988'}, {'text': 'clopidogrel', 'type': 'Chemical', 'start': 1733, 'end': 1744, 'mesh': 'C055162'}]"
+62,12653683,Epithelial sodium channel (ENaC) subunit mRNA and protein expression in rats with puromycin aminonucleoside-induced nephrotic syndrome.,"In experimental nephrotic syndrome, urinary sodium excretion is decreased during the early phase of the disease. The molecular mechanism(s) leading to salt retention has not been completely elucidated. The rate-limiting constituent of collecting duct sodium transport is the epithelial sodium channel (ENaC). We examined the abundance of ENaC subunit mRNAs and proteins in puromycin aminonucleoside (PAN)-induced nephrotic syndrome. The time courses of urinary sodium excretion, plasma aldosterone concentration and proteinuria were studied in male Sprague-Dawley rats treated with a single dose of either PAN or vehicle. The relative amounts of alphaENaC, betaENaC and gammaENaC mRNAs were determined in kidneys from these rats by real-time quantitative TaqMan PCR, and the amounts of proteins by Western blot. The kinetics of urinary sodium excretion and the appearance of proteinuria were comparable with those reported previously. Sodium retention occurred on days 2, 3 and 6 after PAN injection. A significant up-regulation of alphaENaC and betaENaC mRNA abundance on days 1 and 2 preceded sodium retention on days 2 and 3. Conversely, down-regulation of alphaENaC, betaENaC and gammaENaC mRNA expression on day 3 occurred in the presence of high aldosterone concentrations, and was followed by a return of sodium excretion to control values. The amounts of alphaENaC, betaENaC and gammaENaC proteins were not increased during PAN-induced sodium retention. In conclusion, ENaC mRNA expression, especially alphaENaC, is increased in the very early phase of the experimental model of PAN-induced nephrotic syndrome in rats, but appears to escape from the regulation by aldosterone after day 3.","[{'text': 'sodium', 'type': 'Chemical', 'start': 11, 'end': 17, 'mesh': 'D012964'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 82, 'end': 107, 'mesh': 'D011692'}, {'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 116, 'end': 134, 'mesh': 'D009404'}, {'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 152, 'end': 170, 'mesh': 'D009404'}, {'text': 'sodium', 'type': 'Chemical', 'start': 180, 'end': 186, 'mesh': 'D012964'}, {'text': 'sodium', 'type': 'Chemical', 'start': 387, 'end': 393, 'mesh': 'D012964'}, {'text': 'sodium', 'type': 'Chemical', 'start': 422, 'end': 428, 'mesh': 'D012964'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 509, 'end': 534, 'mesh': 'D011692'}, {'text': 'PAN', 'type': 'Chemical', 'start': 536, 'end': 539, 'mesh': 'D011692'}, {'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 549, 'end': 567, 'mesh': 'D009404'}, {'text': 'sodium', 'type': 'Chemical', 'start': 597, 'end': 603, 'mesh': 'D012964'}, {'text': 'aldosterone', 'type': 'Chemical', 'start': 622, 'end': 633, 'mesh': 'D000450'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 652, 'end': 663, 'mesh': 'D011507'}, {'text': 'PAN', 'type': 'Chemical', 'start': 742, 'end': 745, 'mesh': 'D011692'}, {'text': 'sodium', 'type': 'Chemical', 'start': 972, 'end': 978, 'mesh': 'D012964'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1011, 'end': 1022, 'mesh': 'D011507'}, {'text': 'Sodium', 'type': 'Chemical', 'start': 1071, 'end': 1077, 'mesh': 'D012964'}, {'text': 'PAN', 'type': 'Chemical', 'start': 1122, 'end': 1125, 'mesh': 'D011692'}, {'text': 'sodium', 'type': 'Chemical', 'start': 1231, 'end': 1237, 'mesh': 'D012964'}, {'text': 'aldosterone', 'type': 'Chemical', 'start': 1388, 'end': 1399, 'mesh': 'D000450'}, {'text': 'sodium', 'type': 'Chemical', 'start': 1448, 'end': 1454, 'mesh': 'D012964'}, {'text': 'PAN', 'type': 'Chemical', 'start': 1568, 'end': 1571, 'mesh': 'D011692'}, {'text': 'sodium', 'type': 'Chemical', 'start': 1580, 'end': 1586, 'mesh': 'D012964'}, {'text': 'PAN', 'type': 'Chemical', 'start': 1723, 'end': 1726, 'mesh': 'D011692'}, {'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 1735, 'end': 1753, 'mesh': 'D009404'}, {'text': 'aldosterone', 'type': 'Chemical', 'start': 1808, 'end': 1819, 'mesh': 'D000450'}]"
+63,14659530,NO-induced migraine attack: strong increase in plasma calcitonin gene-related peptide (CGRP) concentration and negative correlation with platelet serotonin release.,"The aim of the present study was to investigate changes in the plasma calcitonin gene-related peptide (CGRP) concentration and platelet serotonin (5-hydroxytriptamine, 5-HT) content during the immediate headache and the delayed genuine migraine attack provoked by nitroglycerin. Fifteen female migraineurs (without aura) and eight controls participated in the study. Sublingual nitroglycerin (0.5 mg) was administered. Blood was collected from the antecubital vein four times: 60 min before and after the nitroglycerin application, and 60 and 120 min after the beginning of the migraine attack (mean 344 and 404 min; 12 subjects). In those subjects who had no migraine attack (11 subjects) a similar time schedule was used. Plasma CGRP concentration increased significantly (P<0.01) during the migraine attack and returned to baseline after the cessation of the migraine. In addition, both change and peak, showed significant positive correlations with migraine headache intensity (P<0.001). However, plasma CGRP concentrations failed to change during immediate headache and in the subjects with no migraine attack. Basal CGRP concentration was significantly higher and platelet 5-HT content tended to be lower in subjects who experienced a migraine attack. Platelet serotonin content decreased significantly (P<0.01) after nitroglycerin in subjects with no migraine attack but no consistent change was observed in patients with migraine attack. In conclusion, the fact that plasma CGRP concentration correlates with the timing and severity of a migraine headache suggests a direct relationship between CGRP and migraine. In contrast, serotonin release from platelets does not provoke migraine, it may even counteract the headache and the concomitant CGRP release in this model.","[{'text': 'NO', 'type': 'Chemical', 'start': 0, 'end': 2, 'mesh': 'D009569'}, {'text': 'migraine', 'type': 'Disease', 'start': 11, 'end': 19, 'mesh': 'D008881'}, {'text': 'calcitonin gene-related peptide', 'type': 'Chemical', 'start': 54, 'end': 85, 'mesh': 'D015740'}, {'text': 'CGRP', 'type': 'Chemical', 'start': 87, 'end': 91, 'mesh': 'D015740'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 146, 'end': 155, 'mesh': 'D012701'}, {'text': 'calcitonin gene-related peptide', 'type': 'Chemical', 'start': 235, 'end': 266, 'mesh': 'D015740'}, {'text': 'CGRP', 'type': 'Chemical', 'start': 268, 'end': 272, 'mesh': 'D015740'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 301, 'end': 310, 'mesh': 'D012701'}, {'text': '5-hydroxytriptamine', 'type': 'Chemical', 'start': 312, 'end': 331, 'mesh': 'D012701'}, {'text': '5-HT', 'type': 'Chemical', 'start': 333, 'end': 337, 'mesh': 'D012701'}, {'text': 'headache', 'type': 'Disease', 'start': 368, 'end': 376, 'mesh': 'D006261'}, {'text': 'migraine', 'type': 'Disease', 'start': 401, 'end': 409, 'mesh': 'D008881'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 429, 'end': 442, 'mesh': 'D005996'}, {'text': 'migraineurs (without aura)', 'type': 'Disease', 'start': 459, 'end': 485, 'mesh': 'D020326'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 543, 'end': 556, 'mesh': 'D005996'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 670, 'end': 683, 'mesh': 'D005996'}, {'text': 'migraine', 'type': 'Disease', 'start': 743, 'end': 751, 'mesh': 'D008881'}, {'text': 'migraine', 'type': 'Disease', 'start': 825, 'end': 833, 'mesh': 'D008881'}, {'text': 'CGRP', 'type': 'Chemical', 'start': 896, 'end': 900, 'mesh': 'D015740'}, {'text': 'migraine', 'type': 'Disease', 'start': 959, 'end': 967, 'mesh': 'D008881'}, {'text': 'migraine', 'type': 'Disease', 'start': 1027, 'end': 1035, 'mesh': 'D008881'}, {'text': 'migraine', 'type': 'Disease', 'start': 1118, 'end': 1126, 'mesh': 'D008881'}, {'text': 'headache', 'type': 'Disease', 'start': 1127, 'end': 1135, 'mesh': 'D006261'}, {'text': 'CGRP', 'type': 'Chemical', 'start': 1173, 'end': 1177, 'mesh': 'D015740'}, {'text': 'headache', 'type': 'Disease', 'start': 1227, 'end': 1235, 'mesh': 'D006261'}, {'text': 'migraine', 'type': 'Disease', 'start': 1264, 'end': 1272, 'mesh': 'D008881'}, {'text': 'CGRP', 'type': 'Chemical', 'start': 1287, 'end': 1291, 'mesh': 'D015740'}, {'text': '5-HT', 'type': 'Chemical', 'start': 1344, 'end': 1348, 'mesh': 'D012701'}, {'text': 'migraine', 'type': 'Disease', 'start': 1406, 'end': 1414, 'mesh': 'D008881'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 1432, 'end': 1441, 'mesh': 'D012701'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 1489, 'end': 1502, 'mesh': 'D005996'}, {'text': 'migraine', 'type': 'Disease', 'start': 1523, 'end': 1531, 'mesh': 'D008881'}, {'text': 'migraine', 'type': 'Disease', 'start': 1594, 'end': 1602, 'mesh': 'D008881'}, {'text': 'CGRP', 'type': 'Chemical', 'start': 1647, 'end': 1651, 'mesh': 'D015740'}, {'text': 'migraine', 'type': 'Disease', 'start': 1711, 'end': 1719, 'mesh': 'D008881'}, {'text': 'headache', 'type': 'Disease', 'start': 1720, 'end': 1728, 'mesh': 'D006261'}, {'text': 'CGRP', 'type': 'Chemical', 'start': 1768, 'end': 1772, 'mesh': 'D015740'}, {'text': 'migraine', 'type': 'Disease', 'start': 1777, 'end': 1785, 'mesh': 'D008881'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 1800, 'end': 1809, 'mesh': 'D012701'}, {'text': 'migraine', 'type': 'Disease', 'start': 1850, 'end': 1858, 'mesh': 'D008881'}, {'text': 'headache', 'type': 'Disease', 'start': 1887, 'end': 1895, 'mesh': 'D006261'}, {'text': 'CGRP', 'type': 'Chemical', 'start': 1916, 'end': 1920, 'mesh': 'D015740'}]"
+64,15804801,Coronary aneurysm after implantation of a paclitaxel-eluting stent.,"Formation of coronary aneurysm is a rare complication of stenting with bare metal stents, but based on experimental studies drug-eluting stents may induce toxic effects on the vessel wall with incomplete stent apposition, aneurysm formation and with the potential of stent thrombosis or vessel rupture. We present a 43-year-old man who developed a coronary aneurysm in the right coronary artery 6 months after receiving a paclitaxel-eluting stent. The patient was asymptomatic and the aneurysm was detected in a routine control. Angiography and intracoronary ultrasound demonstrated lack of contact between stent and vessel wall in a 15-mm long segment with maximal aneurysm diameter of 6.0 mm. The patient was successfully treated with a graft stent.","[{'text': 'Coronary aneurysm', 'type': 'Disease', 'start': 0, 'end': 17, 'mesh': 'D003323'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 42, 'end': 52, 'mesh': 'D017239'}, {'text': 'coronary aneurysm', 'type': 'Disease', 'start': 81, 'end': 98, 'mesh': 'D003323'}, {'text': 'aneurysm', 'type': 'Disease', 'start': 290, 'end': 298, 'mesh': 'D000783'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 341, 'end': 351, 'mesh': 'D013927'}, {'text': 'vessel rupture', 'type': 'Disease', 'start': 355, 'end': 369, 'mesh': '-1'}, {'text': 'coronary aneurysm', 'type': 'Disease', 'start': 416, 'end': 433, 'mesh': 'D003323'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 490, 'end': 500, 'mesh': 'D017239'}, {'text': 'aneurysm', 'type': 'Disease', 'start': 553, 'end': 561, 'mesh': 'D000783'}, {'text': 'aneurysm', 'type': 'Disease', 'start': 734, 'end': 742, 'mesh': 'D000783'}]"
+65,16160878,Behavioral effects of urotensin-II centrally administered in mice.,"Urotensin-II (U-II) receptors are widely distributed in the central nervous system. Intracerebroventricular (i.c.v.) injection of U-II causes hypertension and bradycardia and stimulates prolactin and thyrotropin secretion. However, the behavioral effects of centrally administered U-II have received little attention. In the present study, we tested the effects of i.c.v. injections of U-II on behavioral, metabolic, and endocrine responses in mice. Administration of graded doses of U-II (1-10,000 ng/mouse) provoked: (1) a dose-dependent reduction in the number of head dips in the hole-board test; (2) a dose-dependent reduction in the number of entries in the white chamber in the black-and-white compartment test, and in the number of entries in the central platform and open arms in the plus-maze test; and (3) a dose-dependent increase in the duration of immobility in the forced-swimming test and tail suspension test. Intracerebroventricular injection of U-II also caused an increase in: food intake at doses of 100 and 1,000 ng/mouse, water intake at doses of 100-10,000 ng/mouse, and horizontal locomotion activity at a dose of 10,000 ng/mouse. Whatever was the dose, the central administration of U-II had no effect on body temperature, nociception, apomorphine-induced penile erection and climbing behavior, and stress-induced plasma corticosterone level. Taken together, the present study demonstrates that the central injection of U-II at doses of 1-10,000 ng/mouse induces anxiogenic- and depressant-like effects in mouse. These data suggest that U-II may be involved in some aspects of psychiatric disorders.","[{'text': 'urotensin-II', 'type': 'Chemical', 'start': 22, 'end': 34, 'mesh': 'D014579'}, {'text': 'Urotensin-II', 'type': 'Chemical', 'start': 67, 'end': 79, 'mesh': 'D014579'}, {'text': 'U-II', 'type': 'Chemical', 'start': 81, 'end': 85, 'mesh': 'D014579'}, {'text': 'U-II', 'type': 'Chemical', 'start': 197, 'end': 201, 'mesh': 'D014579'}, {'text': 'hypertension', 'type': 'Disease', 'start': 209, 'end': 221, 'mesh': 'D006973'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 226, 'end': 237, 'mesh': 'D001919'}, {'text': 'U-II', 'type': 'Chemical', 'start': 348, 'end': 352, 'mesh': 'D014579'}, {'text': 'U-II', 'type': 'Chemical', 'start': 453, 'end': 457, 'mesh': 'D014579'}, {'text': 'U-II', 'type': 'Chemical', 'start': 551, 'end': 555, 'mesh': 'D014579'}, {'text': 'U-II', 'type': 'Chemical', 'start': 1031, 'end': 1035, 'mesh': 'D014579'}, {'text': 'U-II', 'type': 'Chemical', 'start': 1276, 'end': 1280, 'mesh': 'D014579'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 1329, 'end': 1340, 'mesh': 'D001058'}, {'text': 'penile erection', 'type': 'Disease', 'start': 1349, 'end': 1364, 'mesh': 'D010409'}, {'text': 'corticosterone', 'type': 'Chemical', 'start': 1414, 'end': 1428, 'mesh': 'D003345'}, {'text': 'U-II', 'type': 'Chemical', 'start': 1513, 'end': 1517, 'mesh': 'D014579'}, {'text': 'U-II', 'type': 'Chemical', 'start': 1630, 'end': 1634, 'mesh': 'D014579'}, {'text': 'psychiatric disorders', 'type': 'Disease', 'start': 1670, 'end': 1691, 'mesh': 'D001523'}]"
+66,16274958,Recurrent dysphonia and acitretin.,"We report the case of a woman complaining of dysphonia while she was treated by acitretin. Her symptoms totally regressed after drug withdrawal and reappeared when acitretin was reintroduced. To our knowledge, this is the first case of acitretin-induced dysphonia. This effect may be related to the pharmacological effect of this drug on mucous membranes.","[{'text': 'dysphonia', 'type': 'Disease', 'start': 10, 'end': 19, 'mesh': 'D055154'}, {'text': 'acitretin', 'type': 'Chemical', 'start': 24, 'end': 33, 'mesh': 'D017255'}, {'text': 'dysphonia', 'type': 'Disease', 'start': 80, 'end': 89, 'mesh': 'D055154'}, {'text': 'acitretin', 'type': 'Chemical', 'start': 115, 'end': 124, 'mesh': 'D017255'}, {'text': 'acitretin', 'type': 'Chemical', 'start': 199, 'end': 208, 'mesh': 'D017255'}, {'text': 'acitretin', 'type': 'Chemical', 'start': 271, 'end': 280, 'mesh': 'D017255'}, {'text': 'dysphonia', 'type': 'Disease', 'start': 289, 'end': 298, 'mesh': 'D055154'}]"
+67,16330766,Pharmacological modulation of pain-related brain activity during normal and central sensitization states in humans.,"Abnormal processing of somatosensory inputs in the central nervous system (central sensitization) is the mechanism accounting for the enhanced pain sensitivity in the skin surrounding tissue injury (secondary hyperalgesia). Secondary hyperalgesia shares clinical characteristics with neurogenic hyperalgesia in patients with neuropathic pain. Abnormal brain responses to somatosensory stimuli have been found in patients with hyperalgesia as well as in normal subjects during experimental central sensitization. The aim of this study was to assess the effects of gabapentin, a drug effective in neuropathic pain patients, on brain processing of nociceptive information in normal and central sensitization states. Using functional magnetic resonance imaging (fMRI) in normal volunteers, we studied the gabapentin-induced modulation of brain activity in response to nociceptive mechanical stimulation of normal skin and capsaicin-induced secondary hyperalgesia. The dose of gabapentin was 1,800 mg per os, in a single administration. We found that (i) gabapentin reduced the activations in the bilateral operculoinsular cortex, independently of the presence of central sensitization; (ii) gabapentin reduced the activation in the brainstem, only during central sensitization; (iii) gabapentin suppressed stimulus-induced deactivations, only during central sensitization; this effect was more robust than the effect on brain activation. The observed drug-induced effects were not due to changes in the baseline fMRI signal. These findings indicate that gabapentin has a measurable antinociceptive effect and a stronger antihyperalgesic effect most evident in the brain areas undergoing deactivation, thus supporting the concept that gabapentin is more effective in modulating nociceptive transmission when central sensitization is present.","[{'text': 'pain', 'type': 'Disease', 'start': 30, 'end': 34, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 259, 'end': 263, 'mesh': 'D010146'}, {'text': 'tissue injury', 'type': 'Disease', 'start': 300, 'end': 313, 'mesh': 'D017695'}, {'text': 'secondary hyperalgesia', 'type': 'Disease', 'start': 315, 'end': 337, 'mesh': 'D006930'}, {'text': 'Secondary hyperalgesia', 'type': 'Disease', 'start': 340, 'end': 362, 'mesh': 'D006930'}, {'text': 'neurogenic hyperalgesia', 'type': 'Disease', 'start': 400, 'end': 423, 'mesh': 'D006930'}, {'text': 'neuropathic pain', 'type': 'Disease', 'start': 441, 'end': 457, 'mesh': 'D009437'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 542, 'end': 554, 'mesh': 'D006930'}, {'text': 'gabapentin', 'type': 'Chemical', 'start': 679, 'end': 689, 'mesh': 'C040029'}, {'text': 'neuropathic pain', 'type': 'Disease', 'start': 711, 'end': 727, 'mesh': 'D009437'}, {'text': 'gabapentin', 'type': 'Chemical', 'start': 917, 'end': 927, 'mesh': 'C040029'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 1034, 'end': 1043, 'mesh': 'D002211'}, {'text': 'secondary hyperalgesia', 'type': 'Disease', 'start': 1052, 'end': 1074, 'mesh': 'D006930'}, {'text': 'gabapentin', 'type': 'Chemical', 'start': 1088, 'end': 1098, 'mesh': 'C040029'}, {'text': 'gabapentin', 'type': 'Chemical', 'start': 1166, 'end': 1176, 'mesh': 'C040029'}, {'text': 'gabapentin', 'type': 'Chemical', 'start': 1303, 'end': 1313, 'mesh': 'C040029'}, {'text': 'gabapentin', 'type': 'Chemical', 'start': 1396, 'end': 1406, 'mesh': 'C040029'}, {'text': 'gabapentin', 'type': 'Chemical', 'start': 1666, 'end': 1676, 'mesh': 'C040029'}, {'text': 'gabapentin', 'type': 'Chemical', 'start': 1846, 'end': 1856, 'mesh': 'C040029'}]"
+68,16574712,MDMA polydrug users show process-specific central executive impairments coupled with impaired social and emotional judgement processes.,"In recent years working memory deficits have been reported in users of MDMA (3,4-methylenedioxymethamphetamine, ecstasy). The current study aimed to assess the impact of MDMA use on three separate central executive processes (set shifting, inhibition and memory updating) and also on ""prefrontal"" mediated social and emotional judgement processes. Fifteen polydrug ecstasy users and 15 polydrug non-ecstasy user controls completed a general drug use questionnaire, the Brixton Spatial Anticipation task (set shifting), Backward Digit Span procedure (memory updating), Inhibition of Return (inhibition), an emotional intelligence scale, the Tromso Social Intelligence Scale and the Dysexecutive Questionnaire (DEX). Compared with MDMA-free polydrug controls, MDMA polydrug users showed impairments in set shifting and memory updating, and also in social and emotional judgement processes. The latter two deficits remained significant after controlling for other drug use. These data lend further support to the proposal that cognitive processes mediated by the prefrontal cortex may be impaired by recreational ecstasy use.","[{'text': 'MDMA', 'type': 'Chemical', 'start': 0, 'end': 4, 'mesh': 'D018817'}, {'text': 'impaired social and emotional judgement processes', 'type': 'Disease', 'start': 85, 'end': 134, 'mesh': 'D003072'}, {'text': 'memory deficits', 'type': 'Disease', 'start': 160, 'end': 175, 'mesh': 'D008569'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 207, 'end': 211, 'mesh': 'D018817'}, {'text': '3,4-methylenedioxymethamphetamine', 'type': 'Chemical', 'start': 213, 'end': 246, 'mesh': 'D018817'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 248, 'end': 255, 'mesh': 'D018817'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 306, 'end': 310, 'mesh': 'D018817'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 501, 'end': 508, 'mesh': 'D018817'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 535, 'end': 542, 'mesh': 'D018817'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 865, 'end': 869, 'mesh': 'D018817'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 894, 'end': 898, 'mesh': 'D018817'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 1246, 'end': 1253, 'mesh': 'D018817'}]"
+69,17111419,Severe citrate toxicity complicating volunteer apheresis platelet donation.,"We report a case of severe citrate toxicity during volunteer donor apheresis platelet collection. The donor was a 40-year-old female, first-time apheresis platelet donor. Past medical history was remarkable for hypertension, hyperlipidemia, and depression. Reported medications included bumetanide, pravastatin, and paroxetine. Thirty minutes from the start of the procedure, the donor noted tingling around the mouth, hands, and feet. She then very rapidly developed acute onset of severe facial and extremity tetany. Empirical treatment with intravenous calcium gluconate was initiated, and muscle contractions slowly subsided over approximately 10 to 15 minutes. The events are consistent with a severe reaction to calcium chelation by sodium citrate anticoagulant resulting in symptomatic systemic hypocalcemia. Upon additional retrospective analysis, it was noted that bumetanide is a loop diuretic that may cause significant hypocalcemia. We conclude that careful screening for medications and underlying conditions predisposing to hypocalcemia is recommended to help prevent severe reactions due to citrate toxicity. Laboratory measurement of pre-procedure serum calcium levels in selected donors may identify cases requiring heightened vigilance. The case also illustrates the importance of maintaining preparedness for managing rare but serious reactions in volunteer apheresis blood donors.","[{'text': 'citrate', 'type': 'Chemical', 'start': 7, 'end': 14, 'mesh': 'C102006'}, {'text': 'toxicity', 'type': 'Disease', 'start': 15, 'end': 23, 'mesh': 'D064420'}, {'text': 'citrate', 'type': 'Chemical', 'start': 103, 'end': 110, 'mesh': 'C102006'}, {'text': 'toxicity', 'type': 'Disease', 'start': 111, 'end': 119, 'mesh': 'D064420'}, {'text': 'hypertension', 'type': 'Disease', 'start': 287, 'end': 299, 'mesh': 'D006973'}, {'text': 'hyperlipidemia', 'type': 'Disease', 'start': 301, 'end': 315, 'mesh': 'D006949'}, {'text': 'depression', 'type': 'Disease', 'start': 321, 'end': 331, 'mesh': 'D003866'}, {'text': 'bumetanide', 'type': 'Chemical', 'start': 363, 'end': 373, 'mesh': 'D002034'}, {'text': 'pravastatin', 'type': 'Chemical', 'start': 375, 'end': 386, 'mesh': 'D017035'}, {'text': 'paroxetine', 'type': 'Chemical', 'start': 392, 'end': 402, 'mesh': 'D017374'}, {'text': 'tetany', 'type': 'Disease', 'start': 587, 'end': 593, 'mesh': 'D013746'}, {'text': 'calcium gluconate', 'type': 'Chemical', 'start': 632, 'end': 649, 'mesh': 'D002125'}, {'text': 'muscle contractions', 'type': 'Disease', 'start': 669, 'end': 688, 'mesh': 'C536214'}, {'text': 'calcium', 'type': 'Chemical', 'start': 794, 'end': 801, 'mesh': 'D002118'}, {'text': 'sodium citrate', 'type': 'Chemical', 'start': 815, 'end': 829, 'mesh': 'C102006'}, {'text': 'hypocalcemia', 'type': 'Disease', 'start': 878, 'end': 890, 'mesh': 'D006996'}, {'text': 'bumetanide', 'type': 'Chemical', 'start': 950, 'end': 960, 'mesh': 'D002034'}, {'text': 'loop diuretic', 'type': 'Chemical', 'start': 966, 'end': 979, 'mesh': 'D049994'}, {'text': 'hypocalcemia', 'type': 'Disease', 'start': 1007, 'end': 1019, 'mesh': 'D006996'}, {'text': 'hypocalcemia', 'type': 'Disease', 'start': 1114, 'end': 1126, 'mesh': 'D006996'}, {'text': 'citrate', 'type': 'Chemical', 'start': 1182, 'end': 1189, 'mesh': 'C102006'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1190, 'end': 1198, 'mesh': 'D064420'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1246, 'end': 1253, 'mesh': 'D002118'}]"
+70,17175308,Proteinuria after conversion to sirolimus in renal transplant recipients.,"Sirolimus (SRL) is a new, potent immunosuppressive agent. More recently, proteinuria has been reported as a consequence of sirolimus therapy, although the mechanism has remained unclear. We retrospectively examined the records of 25 renal transplant patients, who developed or displayed increased proteinuria after SRL conversion. The patient cohort (14 men, 11 women) was treated with SRL as conversion therapy, due to chronic allograft nephropathy (CAN) (n = 15) neoplasia (n = 8); Kaposi's sarcoma, Four skin cancers, One intestinal tumors, One renal cell carsinom) or BK virus nephropathy (n = 2). SRL was started at a mean of 78 +/- 42 (15 to 163) months after transplantation. Mean follow-up on SRL therapy was 20 +/- 12 (6 to 43) months. Proteinuria increased from 0.445 (0 to 1.5) g/d before conversion to 3.2 g/dL (0.2 to 12) after conversion (P = 0.001). Before conversion 8 (32%) patients had no proteinuria, whereas afterwards all patients had proteinuria. In 28% of patients proteinuria remained unchanged, whereas it increased in 68% of patients. In 40% it increased by more than 100%. Twenty-eight percent of patients showed increased proteinuria to the nephrotic range. Biopsies performed in five patients revealed new pathological changes: One membranoproliferative glomerulopathy and interstitial nephritis. These patients showed persistently good graft function. Serum creatinine values did not change significantly: 1.98 +/- 0.8 mg/dL before SRL therapy and 2.53 +/- 1.9 mg/dL at last follow-up (P = .14). Five grafts were lost and the patients returned to dialysis. Five patients displayed CAN and Kaposi's sarcoma. Mean urinary protein of patients who returned to dialysis was 1.26 (0.5 to 3.5) g/d before and 4.7 (3 to 12) g/d after conversion (P = .01). Mean serum creatinine level before conversion was 2.21 mg/dL and thereafter, 4.93 mg/dL (P = .02). Heavy proteinuria was common after the use of SRL as rescue therapy for renal transplantation. Therefore, conversion should be considered for patients who have not developed advanced CAN and proteinuria. The possibility of de novo glomerular pathology under SRL treatment requires further investigation by renal biopsy.","[{'text': 'Proteinuria', 'type': 'Disease', 'start': 0, 'end': 11, 'mesh': 'D011507'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 32, 'end': 41, 'mesh': 'D020123'}, {'text': 'Sirolimus', 'type': 'Chemical', 'start': 74, 'end': 83, 'mesh': 'D020123'}, {'text': 'SRL', 'type': 'Chemical', 'start': 85, 'end': 88, 'mesh': 'D020123'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 147, 'end': 158, 'mesh': 'D011507'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 197, 'end': 206, 'mesh': 'D020123'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 371, 'end': 382, 'mesh': 'D011507'}, {'text': 'SRL', 'type': 'Chemical', 'start': 389, 'end': 392, 'mesh': 'D020123'}, {'text': 'SRL', 'type': 'Chemical', 'start': 460, 'end': 463, 'mesh': 'D020123'}, {'text': 'chronic allograft nephropathy', 'type': 'Disease', 'start': 494, 'end': 523, 'mesh': 'D051436'}, {'text': 'CAN', 'type': 'Disease', 'start': 525, 'end': 528, 'mesh': 'D007674'}, {'text': 'neoplasia', 'type': 'Disease', 'start': 539, 'end': 548, 'mesh': 'D009369'}, {'text': ""Kaposi's sarcoma"", 'type': 'Disease', 'start': 558, 'end': 574, 'mesh': 'D012514'}, {'text': 'skin cancers', 'type': 'Disease', 'start': 581, 'end': 593, 'mesh': 'D012878'}, {'text': 'intestinal tumors', 'type': 'Disease', 'start': 599, 'end': 616, 'mesh': 'D007414'}, {'text': 'renal cell carsinom', 'type': 'Disease', 'start': 622, 'end': 641, 'mesh': 'D002292'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 655, 'end': 666, 'mesh': 'D007674'}, {'text': 'SRL', 'type': 'Chemical', 'start': 676, 'end': 679, 'mesh': 'D020123'}, {'text': 'SRL', 'type': 'Chemical', 'start': 775, 'end': 778, 'mesh': 'D020123'}, {'text': 'Proteinuria', 'type': 'Disease', 'start': 819, 'end': 830, 'mesh': 'D011507'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 981, 'end': 992, 'mesh': 'D011507'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1030, 'end': 1041, 'mesh': 'D011507'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1062, 'end': 1073, 'mesh': 'D011507'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1224, 'end': 1235, 'mesh': 'D011507'}, {'text': 'nephrotic', 'type': 'Disease', 'start': 1243, 'end': 1252, 'mesh': 'D009404'}, {'text': 'membranoproliferative glomerulopathy', 'type': 'Disease', 'start': 1335, 'end': 1371, 'mesh': 'D015433'}, {'text': 'interstitial nephritis', 'type': 'Disease', 'start': 1376, 'end': 1398, 'mesh': 'D009395'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1462, 'end': 1472, 'mesh': 'D003404'}, {'text': 'SRL', 'type': 'Chemical', 'start': 1536, 'end': 1539, 'mesh': 'D020123'}, {'text': 'CAN', 'type': 'Disease', 'start': 1685, 'end': 1688, 'mesh': 'D007674'}, {'text': ""Kaposi's sarcoma"", 'type': 'Disease', 'start': 1693, 'end': 1709, 'mesh': 'D012514'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1863, 'end': 1873, 'mesh': 'D003404'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1957, 'end': 1968, 'mesh': 'D011507'}, {'text': 'SRL', 'type': 'Chemical', 'start': 1997, 'end': 2000, 'mesh': 'D020123'}, {'text': 'CAN', 'type': 'Disease', 'start': 2134, 'end': 2137, 'mesh': 'D007674'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 2142, 'end': 2153, 'mesh': 'D011507'}, {'text': 'SRL', 'type': 'Chemical', 'start': 2209, 'end': 2212, 'mesh': 'D020123'}]"
+71,17244258,In vitro characterization of parasympathetic and sympathetic responses in cyclophosphamide-induced cystitis in the rat.,"In cyclophosphamide-induced cystitis in the rat, detrusor function is impaired and the expression and effects of muscarinic receptors altered. Whether or not the neuronal transmission may be affected by cystitis was presently investigated. Responses of urinary strip preparations from control and cyclophosphamide-pretreated rats to electrical field stimulation and to agonists were assessed in the absence and presence of muscarinic, adrenergic and purinergic receptor antagonists. Generally, atropine reduced contractions, but in contrast to controls, it also reduced responses to low electrical field stimulation intensity (1-5 Hz) in inflamed preparations. In both types, purinoceptor desensitization with alpha,beta-methylene adenosine-5'-triphosphate (alpha,beta-meATP) caused further reductions at low frequencies (<10 Hz). The muscarinic receptor antagonists atropine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) ('M(1)/M(3)/M(5)-selective'), methoctramine ('M(2)-selective') and pirenzepine ('M(1)-selective') antagonized the tonic component of the electrical field stimulation-evoked contractile response more potently than the phasic component. 4-DAMP inhibited the tonic contractions in controls more potently than methoctramine and pirenzepine. In inflamed preparations, the muscarinic receptor antagonism on the phasic component of the electrical field stimulation-evoked contraction was decreased and the pirenzepine and 4-DAMP antagonism on the tonic component was much less efficient than in controls. In contrast to controls, methoctramine increased -- instead of decreased -- the tonic responses at high frequencies. While contractions to carbachol and ATP were the same in inflamed and in control strips when related to a reference potassium response, isoprenaline-induced relaxations were smaller in inflamed strips. Thus, in cystitis substantial changes of the efferent functional responses occur. While postjunctional beta-adrenoceptor-mediated relaxations are reduced, effects by prejunctional inhibitory muscarinic receptors may be increased.","[{'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 74, 'end': 90, 'mesh': 'D003520'}, {'text': 'cystitis', 'type': 'Disease', 'start': 99, 'end': 107, 'mesh': 'D003556'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 123, 'end': 139, 'mesh': 'D003520'}, {'text': 'cystitis', 'type': 'Disease', 'start': 148, 'end': 156, 'mesh': 'D003556'}, {'text': 'cystitis', 'type': 'Disease', 'start': 323, 'end': 331, 'mesh': 'D003556'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 417, 'end': 433, 'mesh': 'D003520'}, {'text': 'atropine', 'type': 'Chemical', 'start': 614, 'end': 622, 'mesh': 'D001285'}, {'text': ""alpha,beta-methylene adenosine-5'-triphosphate"", 'type': 'Chemical', 'start': 830, 'end': 876, 'mesh': 'C002630'}, {'text': 'alpha,beta-meATP', 'type': 'Chemical', 'start': 878, 'end': 894, 'mesh': 'C002630'}, {'text': 'atropine', 'type': 'Chemical', 'start': 987, 'end': 995, 'mesh': 'D001285'}, {'text': '4-diphenylacetoxy-N-methylpiperidine', 'type': 'Chemical', 'start': 997, 'end': 1033, 'mesh': 'C042375'}, {'text': '4-DAMP', 'type': 'Chemical', 'start': 1035, 'end': 1041, 'mesh': 'C042375'}, {'text': 'methoctramine', 'type': 'Chemical', 'start': 1073, 'end': 1086, 'mesh': 'C054938'}, {'text': 'pirenzepine', 'type': 'Chemical', 'start': 1110, 'end': 1121, 'mesh': 'D010890'}, {'text': '4-DAMP', 'type': 'Chemical', 'start': 1278, 'end': 1284, 'mesh': 'C042375'}, {'text': 'methoctramine', 'type': 'Chemical', 'start': 1349, 'end': 1362, 'mesh': 'C054938'}, {'text': 'pirenzepine', 'type': 'Chemical', 'start': 1367, 'end': 1378, 'mesh': 'D010890'}, {'text': 'pirenzepine', 'type': 'Chemical', 'start': 1542, 'end': 1553, 'mesh': 'D010890'}, {'text': '4-DAMP', 'type': 'Chemical', 'start': 1558, 'end': 1564, 'mesh': 'C042375'}, {'text': 'methoctramine', 'type': 'Chemical', 'start': 1666, 'end': 1679, 'mesh': 'C054938'}, {'text': 'carbachol', 'type': 'Chemical', 'start': 1780, 'end': 1789, 'mesh': 'D002217'}, {'text': 'ATP', 'type': 'Chemical', 'start': 1794, 'end': 1797, 'mesh': 'D000255'}, {'text': 'potassium', 'type': 'Chemical', 'start': 1874, 'end': 1883, 'mesh': 'D011188'}, {'text': 'isoprenaline', 'type': 'Chemical', 'start': 1894, 'end': 1906, 'mesh': 'D007545'}, {'text': 'cystitis', 'type': 'Disease', 'start': 1969, 'end': 1977, 'mesh': 'D003556'}]"
+72,18020536,"Associations between use of benzodiazepines or related drugs and health, physical abilities and cognitive function: a non-randomised clinical study in the elderly.","OBJECTIVE: To describe associations between the use of benzodiazepines or related drugs (BZDs/RDs) and health, functional abilities and cognitive function in the elderly. METHODS: A non-randomised clinical study of patients aged > or =65 years admitted to acute hospital wards during 1 month. 164 patients (mean age +/- standard deviation [SD] 81.6 +/- 6.8 years) were admitted. Of these, nearly half (n = 78) had used BZDs/RDs before admission, and the remainder (n = 86) were non-users. Cognitive ability was assessed by the Mini-Mental State Examination (MMSE). Patients scoring > or =20 MMSE sum points were interviewed (n = 79) and questioned regarding symptoms and functional abilities during the week prior to admission. Data on use of BZDs/RDs before admission, current medications and discharge diagnoses were collected from medical records. Health, physical abilities and cognitive function were compared between BZD/RD users and non-users, and adjustments were made for confounding variables. The residual serum concentrations of oxazepam, temazepam and zopiclone were analysed. RESULTS: The mean +/- SD duration of BZD/RD use was 7 +/- 7 years (range 1-31). Two or three BZDs/RDs were concomitantly taken by 26% of users (n = 20). Long-term use of these drugs was associated with female sex and use of a higher number of drugs with effects on the CNS, which tended to be related to diagnosed dementia. After adjustment for these variables as confounders, use of BZDs/RDs was not associated with cognitive function as measured by the MMSE. However, use of BZDs/RDs was associated with dizziness, inability to sleep after awaking at night and tiredness in the mornings during the week prior to admission and with stronger depressive symptoms measured at the beginning of the hospital stay. Use of BZDs/RDs tended to be associated with a reduced ability to walk and shorter night-time sleep during the week prior to admission. A higher residual serum concentration of temazepam correlated with a lower MMSE sum score after adjustment for confounding variables. CONCLUSIONS: Long-term use and concomitant use of more than one BZD/RD were common in elderly patients hospitalised because of acute illnesses. Long-term use was associated with daytime and night-time symptoms indicative of poorer health and potentially caused by the adverse effects of these drugs.","[{'text': 'benzodiazepines', 'type': 'Chemical', 'start': 28, 'end': 43, 'mesh': 'D001569'}, {'text': 'benzodiazepines', 'type': 'Chemical', 'start': 219, 'end': 234, 'mesh': 'D001569'}, {'text': 'BZDs', 'type': 'Chemical', 'start': 253, 'end': 257, 'mesh': 'D001569'}, {'text': 'BZDs', 'type': 'Chemical', 'start': 583, 'end': 587, 'mesh': 'D001569'}, {'text': 'BZDs', 'type': 'Chemical', 'start': 907, 'end': 911, 'mesh': 'D001569'}, {'text': 'oxazepam', 'type': 'Chemical', 'start': 1205, 'end': 1213, 'mesh': 'D010076'}, {'text': 'temazepam', 'type': 'Chemical', 'start': 1215, 'end': 1224, 'mesh': 'D013693'}, {'text': 'zopiclone', 'type': 'Chemical', 'start': 1229, 'end': 1238, 'mesh': 'C515050'}, {'text': 'BZDs', 'type': 'Chemical', 'start': 1347, 'end': 1351, 'mesh': 'D001569'}, {'text': 'dementia', 'type': 'Disease', 'start': 1568, 'end': 1576, 'mesh': 'D003704'}, {'text': 'BZDs', 'type': 'Chemical', 'start': 1638, 'end': 1642, 'mesh': 'D001569'}, {'text': 'BZDs', 'type': 'Chemical', 'start': 1731, 'end': 1735, 'mesh': 'D001569'}, {'text': 'dizziness', 'type': 'Disease', 'start': 1760, 'end': 1769, 'mesh': 'D004244'}, {'text': 'inability to sleep', 'type': 'Disease', 'start': 1771, 'end': 1789, 'mesh': 'D007319'}, {'text': 'tiredness', 'type': 'Disease', 'start': 1817, 'end': 1826, 'mesh': 'D005221'}, {'text': 'depressive symptoms', 'type': 'Disease', 'start': 1896, 'end': 1915, 'mesh': 'D003866'}, {'text': 'BZDs', 'type': 'Chemical', 'start': 1971, 'end': 1975, 'mesh': 'D001569'}, {'text': 'temazepam', 'type': 'Chemical', 'start': 2141, 'end': 2150, 'mesh': 'D013693'}]"
+73,18023325,Acute vocal fold palsy after acute disulfiram intoxication.,"Acute peripheral neuropathy caused by a disulfiram overdose is very rare and there is no report of it leading to vocal fold palsy. A 49-year-old woman was transferred to our department because of quadriparesis, lancinating pain, sensory loss, and paresthesia of the distal limbs. One month previously, she had taken a single high dose of disulfiram (130 tablets of ALCOHOL STOP TAB, Shin-Poong Pharm. Co., Ansan, Korea) in a suicide attempt. She was not an alcoholic. For the first few days after ingestion, she was in a confused state and had mild to moderate ataxia and giddiness. She noticed hoarseness and distally accentuated motor and sensory dysfunction after she had recovered from this state. A nerve conduction study was consistent with severe sensorimotor axonal polyneuropathy. Laryngeal electromyography (thyroarytenoid muscle) showed ample denervation potentials. Laryngoscopy revealed asymmetric vocal fold movements during phonation. Her vocal change and weakness began to improve spontaneously about 3 weeks after transfer. This was a case of acute palsy of the recurrent laryngeal nerve and superimposed severe acute sensorimotor axonal polyneuropathy caused by high-dose disulfiram intoxication.","[{'text': 'vocal fold palsy', 'type': 'Disease', 'start': 6, 'end': 22, 'mesh': 'D014826'}, {'text': 'disulfiram', 'type': 'Chemical', 'start': 35, 'end': 45, 'mesh': 'D004221'}, {'text': 'peripheral neuropathy', 'type': 'Disease', 'start': 66, 'end': 87, 'mesh': 'D010523'}, {'text': 'disulfiram', 'type': 'Chemical', 'start': 100, 'end': 110, 'mesh': 'D004221'}, {'text': 'overdose', 'type': 'Disease', 'start': 111, 'end': 119, 'mesh': 'D062787'}, {'text': 'vocal fold palsy', 'type': 'Disease', 'start': 173, 'end': 189, 'mesh': 'D014826'}, {'text': 'quadriparesis', 'type': 'Disease', 'start': 256, 'end': 269, 'mesh': 'D011782'}, {'text': 'pain', 'type': 'Disease', 'start': 283, 'end': 287, 'mesh': 'D010146'}, {'text': 'sensory loss', 'type': 'Disease', 'start': 289, 'end': 301, 'mesh': 'C580162'}, {'text': 'paresthesia', 'type': 'Disease', 'start': 307, 'end': 318, 'mesh': 'D010292'}, {'text': 'disulfiram', 'type': 'Chemical', 'start': 398, 'end': 408, 'mesh': 'D004221'}, {'text': 'ALCOHOL', 'type': 'Chemical', 'start': 425, 'end': 432, 'mesh': 'D000431'}, {'text': 'ataxia', 'type': 'Disease', 'start': 621, 'end': 627, 'mesh': 'D001259'}, {'text': 'giddiness', 'type': 'Disease', 'start': 632, 'end': 641, 'mesh': 'D004244'}, {'text': 'hoarseness', 'type': 'Disease', 'start': 655, 'end': 665, 'mesh': 'D006685'}, {'text': 'polyneuropathy', 'type': 'Disease', 'start': 834, 'end': 848, 'mesh': 'D011115'}, {'text': 'palsy', 'type': 'Disease', 'start': 1126, 'end': 1131, 'mesh': 'D010243'}, {'text': 'polyneuropathy', 'type': 'Disease', 'start': 1215, 'end': 1229, 'mesh': 'D011115'}, {'text': 'disulfiram', 'type': 'Chemical', 'start': 1250, 'end': 1260, 'mesh': 'D004221'}]"
+74,18208574,Higher optical density of an antigen assay predicts thrombosis in patients with heparin-induced thrombocytopenia.,"OBJECTIVES: To correlate optical density and percent inhibition of a two-step heparin-induced thrombocytopenia (HIT) antigen assay with thrombosis; the assay utilizes reaction inhibition characteristics of a high heparin concentration. PATIENTS AND METHODS: Patients with more than 50% decrease in platelet count or thrombocytopenia (<150 x 10(9)/L) after exposure to heparin, who had a positive two-step antigen assay [optical density (OD) >0.4 and >50 inhibition with high concentration of heparin] were included in the study. RESULTS: Forty of 94 HIT patients had thrombosis at diagnosis; 54/94 had isolated-HIT without thrombosis. Eight of the isolated-HIT patients developed thrombosis within the next 30 d; thus, a total of 48 patients had thrombosis at day 30. At diagnosis there was no significant difference in OD between HIT patients with thrombosis and those with isolated-HIT. However, OD was significantly higher in all patients with thrombosis (n = 48, 1.34 +/- 0.89), including isolated-HIT patients who later developed thrombosis within 30 d (n = 8, 1.84 +/- 0.64) as compared to isolated-HIT patients who did not develop thrombosis (0.96 +/- 0.75; P = 0.011 and P = 0.008). The Receiver Operative Characteristic Curve showed that OD >1.27 in the isolated-HIT group had a significantly higher chance of developing thrombosis by day 30. None of these groups showed significant difference in percent inhibition. Multivariate analysis showed a 2.8-fold increased risk of thrombosis in females. Similarly, thrombotic risk increased with age and OD values. CONCLUSION: Higher OD is associated with significant risk of subsequent thrombosis in patients with isolated-HIT; percent inhibition, however, was not predictive.","[{'text': 'thrombosis', 'type': 'Disease', 'start': 52, 'end': 62, 'mesh': 'D013927'}, {'text': 'heparin', 'type': 'Chemical', 'start': 80, 'end': 87, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 96, 'end': 112, 'mesh': 'D013921'}, {'text': 'heparin', 'type': 'Chemical', 'start': 192, 'end': 199, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 208, 'end': 224, 'mesh': 'D013921'}, {'text': 'HIT', 'type': 'Disease', 'start': 226, 'end': 229, 'mesh': 'D013921'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 250, 'end': 260, 'mesh': 'D013927'}, {'text': 'heparin', 'type': 'Chemical', 'start': 327, 'end': 334, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 430, 'end': 446, 'mesh': 'D013921'}, {'text': 'heparin', 'type': 'Chemical', 'start': 482, 'end': 489, 'mesh': 'D006493'}, {'text': 'heparin', 'type': 'Chemical', 'start': 606, 'end': 613, 'mesh': 'D006493'}, {'text': 'HIT', 'type': 'Disease', 'start': 664, 'end': 667, 'mesh': 'D013921'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 681, 'end': 691, 'mesh': 'D013927'}, {'text': 'HIT', 'type': 'Disease', 'start': 725, 'end': 728, 'mesh': 'D013921'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 737, 'end': 747, 'mesh': 'D013927'}, {'text': 'HIT', 'type': 'Disease', 'start': 771, 'end': 774, 'mesh': 'D013921'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 794, 'end': 804, 'mesh': 'D013927'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 860, 'end': 870, 'mesh': 'D013927'}, {'text': 'HIT', 'type': 'Disease', 'start': 945, 'end': 948, 'mesh': 'D013921'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 963, 'end': 973, 'mesh': 'D013927'}, {'text': 'HIT', 'type': 'Disease', 'start': 998, 'end': 1001, 'mesh': 'D013921'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 1061, 'end': 1071, 'mesh': 'D013927'}, {'text': 'HIT', 'type': 'Disease', 'start': 1116, 'end': 1119, 'mesh': 'D013921'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 1149, 'end': 1159, 'mesh': 'D013927'}, {'text': 'HIT', 'type': 'Disease', 'start': 1219, 'end': 1222, 'mesh': 'D013921'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 1252, 'end': 1262, 'mesh': 'D013927'}, {'text': 'HIT', 'type': 'Disease', 'start': 1386, 'end': 1389, 'mesh': 'D013921'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 1444, 'end': 1454, 'mesh': 'D013927'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 1598, 'end': 1608, 'mesh': 'D013927'}, {'text': 'thrombotic', 'type': 'Disease', 'start': 1632, 'end': 1642, 'mesh': 'D013927'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 1754, 'end': 1764, 'mesh': 'D013927'}, {'text': 'HIT', 'type': 'Disease', 'start': 1791, 'end': 1794, 'mesh': 'D013921'}]"
+75,18343374,Central retinal vein occlusion associated with clomiphene-induced ovulation.,"OBJECTIVE: To report a case of central retinal vein occlusion associated with clomiphene citrate (CC). DESIGN: Case study. SETTING: Ophthalmology clinic of an academic hospital. PATIENT(S): A 36-year-old woman referred from the infertility clinic for blurred vision. INTERVENTION(S): Ophthalmic examination after CC therapy. MAIN OUTCOME MEASURE(S): Central retinal vein occlusion after ovulation induction with CC. RESULT(S): A 36-year-old Chinese woman developed central retinal vein occlusion after eight courses of CC. A search of the literature on the thromboembolic complications of CC does not include this severe ophthalmic complication, although mild visual disturbance after CC intake is not uncommon. CONCLUSION(S): This is the first reported case of central retinal vein occlusion after treatment with CC. Extra caution is warranted in treating infertility patients with CC, and patients should be well informed of this side effect before commencement of therapy.","[{'text': 'retinal vein occlusion', 'type': 'Disease', 'start': 8, 'end': 30, 'mesh': 'D012170'}, {'text': 'clomiphene', 'type': 'Chemical', 'start': 47, 'end': 57, 'mesh': 'D002996'}, {'text': 'retinal vein occlusion', 'type': 'Disease', 'start': 116, 'end': 138, 'mesh': 'D012170'}, {'text': 'clomiphene citrate', 'type': 'Chemical', 'start': 155, 'end': 173, 'mesh': 'D002996'}, {'text': 'CC', 'type': 'Chemical', 'start': 175, 'end': 177, 'mesh': 'D002996'}, {'text': 'infertility', 'type': 'Disease', 'start': 305, 'end': 316, 'mesh': 'D007247'}, {'text': 'blurred vision', 'type': 'Disease', 'start': 328, 'end': 342, 'mesh': 'D014786'}, {'text': 'CC', 'type': 'Chemical', 'start': 390, 'end': 392, 'mesh': 'D002996'}, {'text': 'retinal vein occlusion', 'type': 'Disease', 'start': 435, 'end': 457, 'mesh': 'D012170'}, {'text': 'CC', 'type': 'Chemical', 'start': 489, 'end': 491, 'mesh': 'D002996'}, {'text': 'retinal vein occlusion', 'type': 'Disease', 'start': 550, 'end': 572, 'mesh': 'D012170'}, {'text': 'CC', 'type': 'Chemical', 'start': 596, 'end': 598, 'mesh': 'D002996'}, {'text': 'thromboembolic', 'type': 'Disease', 'start': 634, 'end': 648, 'mesh': 'D013923'}, {'text': 'CC', 'type': 'Chemical', 'start': 666, 'end': 668, 'mesh': 'D002996'}, {'text': 'visual disturbance', 'type': 'Disease', 'start': 737, 'end': 755, 'mesh': 'D014786'}, {'text': 'CC', 'type': 'Chemical', 'start': 762, 'end': 764, 'mesh': 'D002996'}, {'text': 'retinal vein occlusion', 'type': 'Disease', 'start': 847, 'end': 869, 'mesh': 'D012170'}, {'text': 'CC', 'type': 'Chemical', 'start': 891, 'end': 893, 'mesh': 'D002996'}, {'text': 'infertility', 'type': 'Disease', 'start': 934, 'end': 945, 'mesh': 'D007247'}, {'text': 'CC', 'type': 'Chemical', 'start': 960, 'end': 962, 'mesh': 'D002996'}]"
+76,18417364,Nicotine-induced nystagmus correlates with midpontine activation.,"The pathomechanism of nicotine-induced nystagmus (NIN) is unknown. The aim of this study was to delineate brain structures that are involved in NIN generation. Eight healthy volunteers inhaled nicotine in darkness during a functional magnetic resonance imaging (fMRI) experiment; eye movements were registered using video-oculography. NIN correlated with blood oxygen level-dependent (BOLD) activity levels in a midpontine site in the posterior basis pontis. NIN-induced midpontine activation may correspond to activation of the dorsomedial pontine nuclei and the nucleus reticularis tegmenti pontis, structures known to participate in the generation of multidirectional saccades and smooth pursuit eye movements.","[{'text': 'Nicotine', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D009538'}, {'text': 'nystagmus', 'type': 'Disease', 'start': 17, 'end': 26, 'mesh': 'D009759'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 88, 'end': 96, 'mesh': 'D009538'}, {'text': 'nystagmus', 'type': 'Disease', 'start': 105, 'end': 114, 'mesh': 'D009759'}, {'text': 'NIN', 'type': 'Disease', 'start': 116, 'end': 119, 'mesh': 'D009759'}, {'text': 'NIN', 'type': 'Disease', 'start': 210, 'end': 213, 'mesh': 'D009759'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 259, 'end': 267, 'mesh': 'D009538'}, {'text': 'NIN', 'type': 'Disease', 'start': 401, 'end': 404, 'mesh': 'D009759'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 427, 'end': 433, 'mesh': 'D010100'}, {'text': 'NIN', 'type': 'Disease', 'start': 525, 'end': 528, 'mesh': 'D009759'}]"
+77,18442015,Protective effect of verapamil on gastric hemorrhagic ulcers in severe atherosclerotic rats.,"Studies concerning with pathogenesis of gastric hemorrhage and mucosal ulceration produced in atherosclerotic rats are lacking. The aim of this study is to examine the role of gastric acid back-diffusion, mast cell histamine release, lipid peroxide (LPO) generation and mucosal microvascular permeability in modulating gastric hemorrhage and ulcer in rats with atherosclerosis induced by coadministration of vitamin D2 and cholesterol. Additionally, the protective effect of verapamil on this ulcer model was evaluated. Male Wistar rats were challenged intragastrically once daily for 9 days with 1.0 ml/kg of corn oil containing vitamin D2 and cholesterol to induce atherosclerosis. Control rats received corn oil only. After gastric surgery, rat stomachs were irrigated for 3 h with either simulated gastric juice or normal saline. Gastric acid back-diffusion, mucosal LPO generation, histamine concentration, microvascular permeability, luminal hemoglobin content and ulcer areas were determined. Elevated atherosclerotic parameters, such as serum calcium, total cholesterol and low-density lipoprotein concentration were obtained in atherosclerotic rats. Severe gastric ulcers accompanied with increased ulcerogenic factors, including gastric acid back-diffusion, histamine release, LPO generation and luminal hemoglobin content were also observed in these rats. Moreover, a positive correlation of histamine to gastric hemorrhage and to ulcer was found in those atherosclerotic rats. This hemorrhagic ulcer and various ulcerogenic parameters were dose-dependently ameliorated by daily intragastric verapamil. Atherosclerosis could produce gastric hemorrhagic ulcer via aggravation of gastric acid back-diffusion, LPO generation, histamine release and microvascular permeability that could be ameliorated by verapamil in rats.","[{'text': 'verapamil', 'type': 'Chemical', 'start': 21, 'end': 30, 'mesh': 'D014700'}, {'text': 'gastric hemorrhagic', 'type': 'Disease', 'start': 34, 'end': 53, 'mesh': 'D006471'}, {'text': 'ulcers', 'type': 'Disease', 'start': 54, 'end': 60, 'mesh': 'D014456'}, {'text': 'atherosclerotic', 'type': 'Disease', 'start': 71, 'end': 86, 'mesh': 'D050197'}, {'text': 'gastric hemorrhage', 'type': 'Disease', 'start': 133, 'end': 151, 'mesh': 'D006471'}, {'text': 'atherosclerotic', 'type': 'Disease', 'start': 187, 'end': 202, 'mesh': 'D050197'}, {'text': 'histamine', 'type': 'Chemical', 'start': 308, 'end': 317, 'mesh': 'D006632'}, {'text': 'gastric hemorrhage', 'type': 'Disease', 'start': 412, 'end': 430, 'mesh': 'D006471'}, {'text': 'ulcer', 'type': 'Disease', 'start': 435, 'end': 440, 'mesh': 'D014456'}, {'text': 'atherosclerosis', 'type': 'Disease', 'start': 454, 'end': 469, 'mesh': 'D050197'}, {'text': 'vitamin D2', 'type': 'Chemical', 'start': 501, 'end': 511, 'mesh': 'D004872'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 516, 'end': 527, 'mesh': 'D002784'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 568, 'end': 577, 'mesh': 'D014700'}, {'text': 'ulcer', 'type': 'Disease', 'start': 586, 'end': 591, 'mesh': 'D014456'}, {'text': 'vitamin D2', 'type': 'Chemical', 'start': 723, 'end': 733, 'mesh': 'D004872'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 738, 'end': 749, 'mesh': 'D002784'}, {'text': 'atherosclerosis', 'type': 'Disease', 'start': 760, 'end': 775, 'mesh': 'D050197'}, {'text': 'histamine', 'type': 'Chemical', 'start': 980, 'end': 989, 'mesh': 'D006632'}, {'text': 'luminal', 'type': 'Chemical', 'start': 1033, 'end': 1040, 'mesh': 'D010634'}, {'text': 'ulcer', 'type': 'Disease', 'start': 1064, 'end': 1069, 'mesh': 'D014456'}, {'text': 'atherosclerotic', 'type': 'Disease', 'start': 1102, 'end': 1117, 'mesh': 'D050197'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1144, 'end': 1151, 'mesh': 'D002118'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 1159, 'end': 1170, 'mesh': 'D002784'}, {'text': 'atherosclerotic', 'type': 'Disease', 'start': 1230, 'end': 1245, 'mesh': 'D050197'}, {'text': 'ulcers', 'type': 'Disease', 'start': 1267, 'end': 1273, 'mesh': 'D014456'}, {'text': 'histamine', 'type': 'Chemical', 'start': 1361, 'end': 1370, 'mesh': 'D006632'}, {'text': 'luminal', 'type': 'Chemical', 'start': 1399, 'end': 1406, 'mesh': 'D010634'}, {'text': 'histamine', 'type': 'Chemical', 'start': 1496, 'end': 1505, 'mesh': 'D006632'}, {'text': 'gastric hemorrhage', 'type': 'Disease', 'start': 1509, 'end': 1527, 'mesh': 'D006471'}, {'text': 'ulcer', 'type': 'Disease', 'start': 1535, 'end': 1540, 'mesh': 'D014456'}, {'text': 'atherosclerotic', 'type': 'Disease', 'start': 1560, 'end': 1575, 'mesh': 'D050197'}, {'text': 'hemorrhagic', 'type': 'Disease', 'start': 1587, 'end': 1598, 'mesh': 'D006471'}, {'text': 'ulcer', 'type': 'Disease', 'start': 1599, 'end': 1604, 'mesh': 'D014456'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 1696, 'end': 1705, 'mesh': 'D014700'}, {'text': 'Atherosclerosis', 'type': 'Disease', 'start': 1707, 'end': 1722, 'mesh': 'D050197'}, {'text': 'gastric hemorrhagic', 'type': 'Disease', 'start': 1737, 'end': 1756, 'mesh': 'D006471'}, {'text': 'ulcer', 'type': 'Disease', 'start': 1757, 'end': 1762, 'mesh': 'D014456'}, {'text': 'histamine', 'type': 'Chemical', 'start': 1827, 'end': 1836, 'mesh': 'D006632'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 1905, 'end': 1914, 'mesh': 'D014700'}]"
+78,18619688,Adriamycin-induced autophagic cardiomyocyte death plays a pathogenic role in a rat model of heart failure.,"BACKGROUND: The mechanisms underlying heart failure induced by adriamycin are very complicated and still unclear. The aim of this study was to investigate whether autophagy was involved in the progression of heart failure induced by adriamycin, so that we can develop a novel treatment strategy for heart failure. METHODS: 3-methyladenine (3MA), a specific inhibitor on autophagy was used in a heart failure model of rats induced by adriamycin. Neonatal cardiomyocytes were isolated from Sprague-Dawley rat hearts and randomly divided into controls, an adriamycin-treated group, and a 3MA plus adriamycin-treated group. We then examined the morphology, expression of beclin 1 gene, mitochondrial permeability transition (MPT), and Na+-K+ ATPase activity in vivo. We also assessed cell viability, mitochondrial membrane potential changes and counted autophagic vacuoles in cultured cardiomyocytes. In addition, we analyzed the expression of autophagy associated gene, beclin 1 using RT-PCR and Western blotting in an animal model. RESULTS: 3MA significantly improved cardiac function and reduced mitochondrial injury. Furthermore, adriamycin induced the formation of autophagic vacuoles, and 3MA strongly downregulated the expression of beclin 1 in adriamycin-induced failing heart and inhibited the formation of autophagic vacuoles. CONCLUSION: Autophagic cardiomyocyte death plays an important role in the pathogenesis of heart failure in rats induced by adriamycin. Mitochondrial injury may be involved in the progression of heart failure caused by adriamycin via the autophagy pathway.","[{'text': 'Adriamycin', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D004317'}, {'text': 'death', 'type': 'Disease', 'start': 44, 'end': 49, 'mesh': 'D003643'}, {'text': 'heart failure', 'type': 'Disease', 'start': 92, 'end': 105, 'mesh': 'D006333'}, {'text': 'heart failure', 'type': 'Disease', 'start': 145, 'end': 158, 'mesh': 'D006333'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 170, 'end': 180, 'mesh': 'D004317'}, {'text': 'heart failure', 'type': 'Disease', 'start': 315, 'end': 328, 'mesh': 'D006333'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 340, 'end': 350, 'mesh': 'D004317'}, {'text': 'heart failure', 'type': 'Disease', 'start': 406, 'end': 419, 'mesh': 'D006333'}, {'text': '3-methyladenine', 'type': 'Chemical', 'start': 430, 'end': 445, 'mesh': 'C025946'}, {'text': '3MA', 'type': 'Chemical', 'start': 447, 'end': 450, 'mesh': 'C025946'}, {'text': 'heart failure', 'type': 'Disease', 'start': 501, 'end': 514, 'mesh': 'D006333'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 540, 'end': 550, 'mesh': 'D004317'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 660, 'end': 670, 'mesh': 'D004317'}, {'text': '3MA', 'type': 'Chemical', 'start': 692, 'end': 695, 'mesh': 'C025946'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 701, 'end': 711, 'mesh': 'D004317'}, {'text': 'K', 'type': 'Chemical', 'start': 842, 'end': 843, 'mesh': 'D011188'}, {'text': '3MA', 'type': 'Chemical', 'start': 1146, 'end': 1149, 'mesh': 'C025946'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 1237, 'end': 1247, 'mesh': 'D004317'}, {'text': '3MA', 'type': 'Chemical', 'start': 1298, 'end': 1301, 'mesh': 'C025946'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 1355, 'end': 1365, 'mesh': 'D004317'}, {'text': 'death', 'type': 'Disease', 'start': 1477, 'end': 1482, 'mesh': 'D003643'}, {'text': 'heart failure', 'type': 'Disease', 'start': 1530, 'end': 1543, 'mesh': 'D006333'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 1563, 'end': 1573, 'mesh': 'D004317'}, {'text': 'heart failure', 'type': 'Disease', 'start': 1634, 'end': 1647, 'mesh': 'D006333'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 1658, 'end': 1668, 'mesh': 'D004317'}]"
+79,19308880,"Confusion, a rather serious adverse drug reaction with valproic acid: a review of the French Pharmacovigilance database.","INTRODUCTION: Confusion is an adverse drug reaction frequently observed with valproic acid. Some case reports are published in the literature but no systematic study from a sample of patients has been published. We performed this study in order to describe the main characteristics of this adverse drug reaction. METHODS: Using the French Pharmacovigilance database, we selected the cases of confusion reported since 1985 with valproic acid. RESULTS: 272 cases of confusion were reported with valproic acid: 153 women and 119 men. Confusion mostly occurred during the two first weeks following valproic acid exposure (39.7%). It was ""serious"" for almost 2/3 of the patients (62.5%) and its outcome favourable in most of the cases (82%). The occurrence of this ADR was more frequent in patients aged between 61 and 80 years. CONCLUSION: This work shows that confusion with valproic acid is a serious, rather frequent but reversible adverse drug reaction. It occurs especially in older patients and during the first two weeks of treatment.","[{'text': 'Confusion', 'type': 'Disease', 'start': 0, 'end': 9, 'mesh': 'D003221'}, {'text': 'valproic acid', 'type': 'Chemical', 'start': 55, 'end': 68, 'mesh': 'D014635'}, {'text': 'Confusion', 'type': 'Disease', 'start': 135, 'end': 144, 'mesh': 'D003221'}, {'text': 'valproic acid', 'type': 'Chemical', 'start': 198, 'end': 211, 'mesh': 'D014635'}, {'text': 'confusion', 'type': 'Disease', 'start': 513, 'end': 522, 'mesh': 'D003221'}, {'text': 'valproic acid', 'type': 'Chemical', 'start': 548, 'end': 561, 'mesh': 'D014635'}, {'text': 'confusion', 'type': 'Disease', 'start': 585, 'end': 594, 'mesh': 'D003221'}, {'text': 'valproic acid', 'type': 'Chemical', 'start': 614, 'end': 627, 'mesh': 'D014635'}, {'text': 'Confusion', 'type': 'Disease', 'start': 652, 'end': 661, 'mesh': 'D003221'}, {'text': 'valproic acid', 'type': 'Chemical', 'start': 715, 'end': 728, 'mesh': 'D014635'}, {'text': 'confusion', 'type': 'Disease', 'start': 978, 'end': 987, 'mesh': 'D003221'}, {'text': 'valproic acid', 'type': 'Chemical', 'start': 993, 'end': 1006, 'mesh': 'D014635'}]"
+80,19631624,Learning and memory deficits in ecstasy users and their neural correlates during a face-learning task.,"It has been consistently shown that ecstasy users display impairments in learning and memory performance. In addition, working memory processing in ecstasy users has been shown to be associated with neural alterations in hippocampal and/or cortical regions as measured by functional magnetic resonance imaging (fMRI). Using functional imaging and a face-learning task, we investigated neural correlates of encoding and recalling face-name associations in 20 recreational drug users whose predominant drug use was ecstasy and 20 controls. To address the potential confounding effects of the cannabis use of the ecstasy using group, a second analysis included 14 previously tested cannabis users (Nestor, L., Roberts, G., Garavan, H., Hester, R., 2008. Deficits in learning and memory: parahippocampal hyperactivity and frontocortical hypoactivity in cannabis users. Neuroimage 40, 1328-1339). Ecstasy users performed significantly worse in learning and memory compared to controls and cannabis users. A conjunction analysis of the encode and recall phases of the task revealed ecstasy-specific hyperactivity in bilateral frontal regions, left temporal, right parietal, bilateral temporal, and bilateral occipital brain regions. Ecstasy-specific hypoactivity was evident in the right dorsal anterior cingulated cortex (ACC) and left posterior cingulated cortex. In both ecstasy and cannabis groups brain activation was decreased in the right medial frontal gyrus, left parahippocampal gyrus, left dorsal cingulate gyrus, and left caudate. These results elucidated ecstasy-related deficits, only some of which might be attributed to cannabis use. These ecstasy-specific effects may be related to the vulnerability of isocortical and allocortical regions to the neurotoxic effects of ecstasy.","[{'text': 'ecstasy', 'type': 'Chemical', 'start': 32, 'end': 39, 'mesh': 'D018817'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 139, 'end': 146, 'mesh': 'D018817'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 251, 'end': 258, 'mesh': 'D018817'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 616, 'end': 623, 'mesh': 'D018817'}, {'text': 'cannabis', 'type': 'Chemical', 'start': 693, 'end': 701, 'mesh': 'D002188'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 713, 'end': 720, 'mesh': 'D018817'}, {'text': 'cannabis', 'type': 'Chemical', 'start': 782, 'end': 790, 'mesh': 'D002188'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 903, 'end': 916, 'mesh': 'D006948'}, {'text': 'cannabis', 'type': 'Chemical', 'start': 952, 'end': 960, 'mesh': 'D002188'}, {'text': 'Ecstasy', 'type': 'Chemical', 'start': 995, 'end': 1002, 'mesh': 'D018817'}, {'text': 'cannabis', 'type': 'Chemical', 'start': 1087, 'end': 1095, 'mesh': 'D002188'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 1179, 'end': 1186, 'mesh': 'D018817'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 1196, 'end': 1209, 'mesh': 'D006948'}, {'text': 'Ecstasy', 'type': 'Chemical', 'start': 1330, 'end': 1337, 'mesh': 'D018817'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 1471, 'end': 1478, 'mesh': 'D018817'}, {'text': 'cannabis', 'type': 'Chemical', 'start': 1483, 'end': 1491, 'mesh': 'D002188'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 1665, 'end': 1672, 'mesh': 'D018817'}, {'text': 'cannabis', 'type': 'Chemical', 'start': 1733, 'end': 1741, 'mesh': 'D002188'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 1753, 'end': 1760, 'mesh': 'D018817'}, {'text': 'neurotoxic', 'type': 'Disease', 'start': 1861, 'end': 1871, 'mesh': 'D020258'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 1883, 'end': 1890, 'mesh': 'D018817'}]"
+81,20003049,Prolonged elevation of plasma argatroban in a cardiac transplant patient with a suspected history of heparin-induced thrombocytopenia with thrombosis.,"BACKGROUND: Direct thrombin inhibitors (DTIs) provide an alternative method of anticoagulation for patients with a history of heparin-induced thrombocytopenia (HIT) or HIT with thrombosis (HITT) undergoing cardiopulmonary bypass (CPB). In the following report, a 65-year-old critically ill patient with a suspected history of HITT was administered argatroban for anticoagulation on bypass during heart transplantation. The patient required massive transfusion support (55 units of red blood cells, 42 units of fresh-frozen plasma, 40 units of cryoprecipitate, 40 units of platelets, and three doses of recombinant Factor VIIa) for severe intraoperative and postoperative bleeding. STUDY DESIGN AND METHODS: Plasma samples from before and after CPB were analyzed postoperatively for argatroban concentration using a modified ecarin clotting time (ECT) assay. RESULTS: Unexpectedly high concentrations of argatroban were measured in these samples (range, 0-32 microg/mL), and a prolonged plasma argatroban half life (t(1/2)) of 514 minutes was observed (published elimination t(1/2) is 39-51 minutes [< or = 181 minutes with hepatic impairment]). CONCLUSIONS: Correlation of plasma argatroban concentration versus the patient's coagulation variables and clinical course suggest that prolonged elevated levels of plasma argatroban may have contributed to the patient's extended coagulopathy. Because DTIs do not have reversal agents, surgical teams and transfusion services should remain aware of the possibility of massive transfusion events during anticoagulation with these agents. This is the first report to measure plasma argatroban concentration in the context of CPB and extended coagulopathy.","[{'text': 'argatroban', 'type': 'Chemical', 'start': 30, 'end': 40, 'mesh': 'C031942'}, {'text': 'heparin', 'type': 'Chemical', 'start': 101, 'end': 108, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 117, 'end': 133, 'mesh': 'D013921'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 139, 'end': 149, 'mesh': 'D013927'}, {'text': 'heparin', 'type': 'Chemical', 'start': 277, 'end': 284, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 293, 'end': 309, 'mesh': 'D013921'}, {'text': 'HIT', 'type': 'Disease', 'start': 311, 'end': 314, 'mesh': 'D013921'}, {'text': 'HIT', 'type': 'Disease', 'start': 319, 'end': 322, 'mesh': 'D013921'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 328, 'end': 338, 'mesh': 'D013927'}, {'text': 'HITT', 'type': 'Disease', 'start': 340, 'end': 344, 'mesh': 'D013921|D013927'}, {'text': 'critically ill', 'type': 'Disease', 'start': 426, 'end': 440, 'mesh': 'D016638'}, {'text': 'HITT', 'type': 'Disease', 'start': 477, 'end': 481, 'mesh': 'D013921|D013927'}, {'text': 'argatroban', 'type': 'Chemical', 'start': 499, 'end': 509, 'mesh': 'C031942'}, {'text': 'argatroban', 'type': 'Chemical', 'start': 933, 'end': 943, 'mesh': 'C031942'}, {'text': 'argatroban', 'type': 'Chemical', 'start': 1054, 'end': 1064, 'mesh': 'C031942'}, {'text': 'argatroban', 'type': 'Chemical', 'start': 1144, 'end': 1154, 'mesh': 'C031942'}, {'text': 'hepatic impairment', 'type': 'Disease', 'start': 1274, 'end': 1292, 'mesh': 'D008107'}, {'text': 'argatroban', 'type': 'Chemical', 'start': 1331, 'end': 1341, 'mesh': 'C031942'}, {'text': 'argatroban', 'type': 'Chemical', 'start': 1468, 'end': 1478, 'mesh': 'C031942'}, {'text': 'coagulopathy', 'type': 'Disease', 'start': 1526, 'end': 1538, 'mesh': 'D001778'}, {'text': 'argatroban', 'type': 'Chemical', 'start': 1776, 'end': 1786, 'mesh': 'C031942'}, {'text': 'coagulopathy', 'type': 'Disease', 'start': 1836, 'end': 1848, 'mesh': 'D001778'}]"
+82,20196116,"Antituberculosis therapy-induced acute liver failure: magnitude, profile, prognosis, and predictors of outcome.","Antituberculosis therapy (ATT)-associated acute liver failure (ATT-ALF) is the commonest drug-induced ALF in South Asia. Prospective studies on ATT-ALF are lacking. The current study prospectively evaluated the magnitude, clinical course, outcome, and prognostic factors in ATT-ALF. From January 1986 to January 2009, 1223 consecutive ALF patients were evaluated: ATT alone was the cause in 70 (5.7%) patients. Another 15 (1.2%) had ATT and simultaneous hepatitis virus infection. In 44 (62.8%) patients, ATT was prescribed empirically without definitive evidence of tuberculosis. ATT-ALF patients were younger (32.87 [+/-15.8] years), and 49 (70%) of them were women. Most had hyperacute presentation; the median icterus encephalopathy interval was 4.5 (0-30) days. The median duration of ATT before ALF was 30 (7-350) days. At presentation, advanced encephalopathy and cerebral edema were present in 51 (76%) and 29 (41.4%) patients, respectively. Gastrointestinal bleed, seizures, infection, and acute renal failure were documented in seven (10%), five (7.1%), 26 (37.1%), and seven (10%) patients, respectively. Compared with hepatitis E virus (HEV) and non-A non-E-induced ALF, ATT-ALF patients had nearly similar presentations except for older age and less elevation of liver enzymes. The mortality rate among patients with ATT-ALF was high (67.1%, n = 47), and only 23 (32.9%) patients recovered with medical treatment. In multivariate analysis, three factors independently predicted mortality: serum bilirubin (>or=10.8 mg/dL), prothrombin time (PT) prolongation (>or=26 seconds), and grade III/IV encephalopathy at presentation. CONCLUSION: ATT-ALF constituted 5.7% of ALF at our center and had a high mortality rate. Because the mortality rate is so high, determining which factors are predictors is less important. A high proportion of patients had consumed ATT empirically, which could have been prevented.","[{'text': 'Antituberculosis', 'type': 'Chemical', 'start': 0, 'end': 16, 'mesh': 'D000995'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 33, 'end': 52, 'mesh': 'D017114'}, {'text': 'Antituberculosis', 'type': 'Chemical', 'start': 112, 'end': 128, 'mesh': 'D000995'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 154, 'end': 173, 'mesh': 'D017114'}, {'text': 'ALF', 'type': 'Disease', 'start': 179, 'end': 182, 'mesh': 'D017114'}, {'text': 'ALF', 'type': 'Disease', 'start': 214, 'end': 217, 'mesh': 'D017114'}, {'text': 'ALF', 'type': 'Disease', 'start': 260, 'end': 263, 'mesh': 'D017114'}, {'text': 'ALF', 'type': 'Disease', 'start': 390, 'end': 393, 'mesh': 'D017114'}, {'text': 'ALF', 'type': 'Disease', 'start': 447, 'end': 450, 'mesh': 'D017114'}, {'text': 'hepatitis virus infection', 'type': 'Disease', 'start': 566, 'end': 591, 'mesh': 'D006525'}, {'text': 'tuberculosis', 'type': 'Disease', 'start': 679, 'end': 691, 'mesh': 'D014376'}, {'text': 'ALF', 'type': 'Disease', 'start': 697, 'end': 700, 'mesh': 'D017114'}, {'text': 'icterus', 'type': 'Disease', 'start': 826, 'end': 833, 'mesh': 'D007565'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 834, 'end': 848, 'mesh': 'D001927'}, {'text': 'ALF', 'type': 'Disease', 'start': 913, 'end': 916, 'mesh': 'D017114'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 964, 'end': 978, 'mesh': 'D001927'}, {'text': 'cerebral edema', 'type': 'Disease', 'start': 983, 'end': 997, 'mesh': 'D001929'}, {'text': 'Gastrointestinal bleed', 'type': 'Disease', 'start': 1062, 'end': 1084, 'mesh': 'D006471'}, {'text': 'seizures', 'type': 'Disease', 'start': 1086, 'end': 1094, 'mesh': 'D012640'}, {'text': 'infection', 'type': 'Disease', 'start': 1096, 'end': 1105, 'mesh': 'D007239'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 1111, 'end': 1130, 'mesh': 'D058186'}, {'text': 'hepatitis E', 'type': 'Disease', 'start': 1242, 'end': 1253, 'mesh': 'D016751'}, {'text': 'ALF', 'type': 'Disease', 'start': 1290, 'end': 1293, 'mesh': 'D017114'}, {'text': 'ALF', 'type': 'Disease', 'start': 1299, 'end': 1302, 'mesh': 'D017114'}, {'text': 'ALF', 'type': 'Disease', 'start': 1446, 'end': 1449, 'mesh': 'D017114'}, {'text': 'bilirubin', 'type': 'Chemical', 'start': 1620, 'end': 1629, 'mesh': 'D001663'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 1718, 'end': 1732, 'mesh': 'D001927'}, {'text': 'ALF', 'type': 'Disease', 'start': 1766, 'end': 1769, 'mesh': 'D017114'}, {'text': 'ALF', 'type': 'Disease', 'start': 1790, 'end': 1793, 'mesh': 'D017114'}]"
+83,20470218,Central nervous system complications during treatment of acute lymphoblastic leukemia in a single pediatric institution.,"Central nervous system (CNS) complications during treatment of childhood acute lymphoblastic leukemia (ALL) remain a challenging clinical problem. Outcome improvement with more intensive chemotherapy has significantly increased the incidence and severity of adverse events. This study analyzed the incidence of neurological complications during ALL treatment in a single pediatric institution, focusing on clinical, radiological, and electrophysiological findings. Exclusion criteria included CNS leukemic infiltration at diagnosis, therapy-related peripheral neuropathy, late-onset encephalopathy, or long-term neurocognitive defects. During a 9-year period, we retrospectively collected 27 neurological events (11%) in as many patients, from 253 children enrolled in the ALL front-line protocol. CNS complications included posterior reversible leukoencephalopathy syndrome (n = 10), stroke (n = 5), temporal lobe epilepsy (n = 2), high-dose methotrexate toxicity (n = 2), syndrome of inappropriate antidiuretic hormone secretion (n = 1), and other unclassified events (n = 7). In conclusion, CNS complications are frequent events during ALL therapy, and require rapid detection and prompt treatment to limit permanent damage.","[{'text': 'Central nervous system complications', 'type': 'Disease', 'start': 0, 'end': 36, 'mesh': 'D002493'}, {'text': 'acute lymphoblastic leukemia', 'type': 'Disease', 'start': 57, 'end': 85, 'mesh': 'D054198'}, {'text': 'Central nervous system (CNS) complications', 'type': 'Disease', 'start': 121, 'end': 163, 'mesh': 'D002493'}, {'text': 'acute lymphoblastic leukemia', 'type': 'Disease', 'start': 194, 'end': 222, 'mesh': 'D054198'}, {'text': 'ALL', 'type': 'Disease', 'start': 224, 'end': 227, 'mesh': 'D054198'}, {'text': 'neurological complications', 'type': 'Disease', 'start': 432, 'end': 458, 'mesh': 'D002493'}, {'text': 'ALL', 'type': 'Disease', 'start': 466, 'end': 469, 'mesh': 'D054198'}, {'text': 'leukemic infiltration', 'type': 'Disease', 'start': 618, 'end': 639, 'mesh': 'D017254'}, {'text': 'peripheral neuropathy', 'type': 'Disease', 'start': 670, 'end': 691, 'mesh': 'D010523'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 704, 'end': 718, 'mesh': 'D001927'}, {'text': 'neurocognitive defects', 'type': 'Disease', 'start': 733, 'end': 755, 'mesh': 'D002493'}, {'text': 'ALL', 'type': 'Disease', 'start': 894, 'end': 897, 'mesh': 'D054198'}, {'text': 'leukoencephalopathy', 'type': 'Disease', 'start': 967, 'end': 986, 'mesh': 'D056784'}, {'text': 'stroke', 'type': 'Disease', 'start': 1006, 'end': 1012, 'mesh': 'D020521'}, {'text': 'temporal lobe epilepsy', 'type': 'Disease', 'start': 1022, 'end': 1044, 'mesh': 'D004833'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 1064, 'end': 1076, 'mesh': 'D008727'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1077, 'end': 1085, 'mesh': 'D064420'}, {'text': 'inappropriate antidiuretic hormone secretion', 'type': 'Disease', 'start': 1107, 'end': 1151, 'mesh': 'D007177'}, {'text': 'ALL', 'type': 'Disease', 'start': 1260, 'end': 1263, 'mesh': 'D054198'}]"
+84,20722491,Safety of capecitabine: a review.,"IMPORTANCE OF THE FIELD: Fluoropyrimidines, in particular 5-fluorouracil (5-FU), have been the mainstay of treatment for several solid tumors, including colorectal, breast and head and neck cancers, for > 40 years. AREAS COVERED IN THIS REVIEW: This article reviews the pharmacology and efficacy of capecitabine with a special emphasis on its safety. WHAT THE READER WILL GAIN: The reader will gain better insight into the safety of capecitabine in special populations such as patients with advanced age, renal and kidney disease. We also explore different dosing and schedules of capecitabine administration. TAKE HOME MESSAGE: Capecitabine is an oral prodrug of 5-FU and was developed to fulfill the need for a more convenient therapy and provide an improved safety/efficacy profile. It has shown promising results alone or in combination with other chemotherapeutic agents in colorectal, breast, pancreaticobiliary, gastric, renal cell and head and neck cancers. The most commonly reported toxic effects of capecitabine are diarrhea, nausea, vomiting, stomatitis and hand-foot syndrome. Capecitabine has a well-established safety profile and can be given safely to patients with advanced age, hepatic and renal dysfunctions.","[{'text': 'capecitabine', 'type': 'Chemical', 'start': 10, 'end': 22, 'mesh': 'C110904'}, {'text': 'Fluoropyrimidines', 'type': 'Chemical', 'start': 59, 'end': 76, 'mesh': '-1'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 92, 'end': 106, 'mesh': 'D005472'}, {'text': '5-FU', 'type': 'Chemical', 'start': 108, 'end': 112, 'mesh': 'D005472'}, {'text': 'tumors', 'type': 'Disease', 'start': 169, 'end': 175, 'mesh': 'D009369'}, {'text': 'capecitabine', 'type': 'Chemical', 'start': 333, 'end': 345, 'mesh': 'C110904'}, {'text': 'capecitabine', 'type': 'Chemical', 'start': 467, 'end': 479, 'mesh': 'C110904'}, {'text': 'renal and kidney disease', 'type': 'Disease', 'start': 539, 'end': 563, 'mesh': 'D007674'}, {'text': 'capecitabine', 'type': 'Chemical', 'start': 615, 'end': 627, 'mesh': 'C110904'}, {'text': 'Capecitabine', 'type': 'Chemical', 'start': 663, 'end': 675, 'mesh': 'C110904'}, {'text': '5-FU', 'type': 'Chemical', 'start': 698, 'end': 702, 'mesh': 'D005472'}, {'text': 'capecitabine', 'type': 'Chemical', 'start': 1044, 'end': 1056, 'mesh': 'C110904'}, {'text': 'diarrhea', 'type': 'Disease', 'start': 1061, 'end': 1069, 'mesh': 'D003967'}, {'text': 'nausea', 'type': 'Disease', 'start': 1071, 'end': 1077, 'mesh': 'D009325'}, {'text': 'vomiting', 'type': 'Disease', 'start': 1079, 'end': 1087, 'mesh': 'D014839'}, {'text': 'stomatitis', 'type': 'Disease', 'start': 1089, 'end': 1099, 'mesh': 'D013280'}, {'text': 'hand-foot syndrome', 'type': 'Disease', 'start': 1104, 'end': 1122, 'mesh': 'D060831'}, {'text': 'Capecitabine', 'type': 'Chemical', 'start': 1124, 'end': 1136, 'mesh': 'C110904'}]"
+85,20882060,Effects of pallidal neurotensin on haloperidol-induced parkinsonian catalepsy: behavioral and electrophysiological studies.,"OBJECTIVE: The globus pallidus plays a critical role in movement regulation. Previous studies have indicated that the globus pallidus receives neurotensinergic innervation from the striatum, and systemic administration of a neurotensin analog could produce antiparkinsonian effects. The present study aimed to investigate the effects of pallidal neurotensin on haloperidol-induced parkinsonian symptoms. METHODS: Behavioral experiments and electrophysiological recordings were performed in the present study. RESULTS: Bilateral infusions of neurotensin into the globus pallidus reversed haloperidol-induced parkinsonian catalepsy in rats. Electrophysiological recordings showed that microinjection of neurotensin induced excitation of pallidal neurons in the presence of systemic haloperidol administration. The neurotensin type-1 receptor antagonist SR48692 blocked both the behavioral and the electrophysiological effects induced by neurotensin. CONCLUSION: Activation of pallidal neurotensin receptors may be involved in neurotensin-induced antiparkinsonian effects.","[{'text': 'neurotensin', 'type': 'Chemical', 'start': 20, 'end': 31, 'mesh': 'D009496'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 35, 'end': 46, 'mesh': 'D006220'}, {'text': 'parkinsonian catalepsy', 'type': 'Disease', 'start': 55, 'end': 77, 'mesh': 'D002375'}, {'text': 'neurotensin', 'type': 'Chemical', 'start': 348, 'end': 359, 'mesh': 'D009496'}, {'text': 'neurotensin', 'type': 'Chemical', 'start': 470, 'end': 481, 'mesh': 'D009496'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 485, 'end': 496, 'mesh': 'D006220'}, {'text': 'parkinsonian symptoms', 'type': 'Disease', 'start': 505, 'end': 526, 'mesh': 'D010302'}, {'text': 'neurotensin', 'type': 'Chemical', 'start': 665, 'end': 676, 'mesh': 'D009496'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 711, 'end': 722, 'mesh': 'D006220'}, {'text': 'parkinsonian catalepsy', 'type': 'Disease', 'start': 731, 'end': 753, 'mesh': 'D002375'}, {'text': 'neurotensin', 'type': 'Chemical', 'start': 825, 'end': 836, 'mesh': 'D009496'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 904, 'end': 915, 'mesh': 'D006220'}, {'text': 'neurotensin type-1 receptor antagonist', 'type': 'Chemical', 'start': 936, 'end': 974, 'mesh': 'C079087'}, {'text': 'SR48692', 'type': 'Chemical', 'start': 975, 'end': 982, 'mesh': 'C079087'}, {'text': 'neurotensin', 'type': 'Chemical', 'start': 1059, 'end': 1070, 'mesh': 'D009496'}, {'text': 'neurotensin', 'type': 'Chemical', 'start': 1107, 'end': 1118, 'mesh': 'D009496'}, {'text': 'neurotensin', 'type': 'Chemical', 'start': 1148, 'end': 1159, 'mesh': 'D009496'}]"
+86,26094,Antihypertensive drugs and depression: a reappraisal.,"Eighty-nine new referral hypertensive out-patients and 46 new referral non-hypertensive chronically physically ill out-patients completed a mood rating scale at regular intervals for one year. The results showed a high prevalence of depression in both groups of patients, with no preponderance in the hypertensive group. Hypertensive patients with psychiatric histories had a higher prevalence of depression than the comparison patients. This was accounted for by a significant number of depressions occurring in methyl dopa treated patients with psychiatric histories.","[{'text': 'depression', 'type': 'Disease', 'start': 27, 'end': 37, 'mesh': 'D003866'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 79, 'end': 91, 'mesh': 'D006973'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 129, 'end': 141, 'mesh': 'D006973'}, {'text': 'depression', 'type': 'Disease', 'start': 287, 'end': 297, 'mesh': 'D003866'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 355, 'end': 367, 'mesh': 'D006973'}, {'text': 'Hypertensive', 'type': 'Disease', 'start': 375, 'end': 387, 'mesh': 'D006973'}, {'text': 'psychiatric', 'type': 'Disease', 'start': 402, 'end': 413, 'mesh': 'D001523'}, {'text': 'depression', 'type': 'Disease', 'start': 451, 'end': 461, 'mesh': 'D003866'}, {'text': 'depressions', 'type': 'Disease', 'start': 542, 'end': 553, 'mesh': 'D003866'}, {'text': 'methyl dopa', 'type': 'Chemical', 'start': 567, 'end': 578, 'mesh': 'D008750'}, {'text': 'psychiatric', 'type': 'Disease', 'start': 601, 'end': 612, 'mesh': 'D001523'}]"
+87,322550,Pulmonary shunt and cardiovascular responses to CPAP during nitroprusside-induced hypotension.,"The effects of continuous positive airway pressure (CPAP) on cardiovascular dynamics and pulmonary shunt (QS/QT) were investigated in 12 dogs before and during sodium nitroprusside infusion that decreased mean arterial blood pressure 40-50 per cent. Before nitroprusside infusion, 5 cm H2O CPAP significantly, P less than .05, decreased arterial blood pressure, but did not significantly alter heart rate, cardiac output, systemic vascular resistance, or QS/QT. Ten cm H2O CPAP before nitroprusside infusion produced a further decrease in arterial blood pressure and significantly increased heart rate and decreased cardiac output and QS/QT. Nitroprusside caused significant decreases in arterial blood pressure and systemic vascular resistance and increases in heart rate, but did not change cardiac output or QS/QT. Five cm H2O CPAP during nitroprusside did not further alter any of the above-mentioned variables. However, 10 cm H2O CPAP decreased arterial blood pressure, cardiac output, and QS/QT. These data indicate that nitroprusside infusion rates that decrease mean arterial blood pressure by 40-50 per cent do not change cardiac output or QS/QT. During nitroprusside infusion low levels of CPAP do not markedly alter cardiovascular dynamics, but high levels of CPAP (10 cm H2O), while decreasing QS/QT, produce marked decreases in arterial blood pressure and cardiac output.","[{'text': 'nitroprusside', 'type': 'Chemical', 'start': 60, 'end': 73, 'mesh': 'D009599'}, {'text': 'hypotension', 'type': 'Disease', 'start': 82, 'end': 93, 'mesh': 'D007022'}, {'text': 'sodium nitroprusside', 'type': 'Chemical', 'start': 255, 'end': 275, 'mesh': 'D009599'}, {'text': 'nitroprusside', 'type': 'Chemical', 'start': 352, 'end': 365, 'mesh': 'D009599'}, {'text': 'H2O', 'type': 'Chemical', 'start': 381, 'end': 384, 'mesh': 'D014867'}, {'text': 'H2O', 'type': 'Chemical', 'start': 564, 'end': 567, 'mesh': 'D014867'}, {'text': 'nitroprusside', 'type': 'Chemical', 'start': 580, 'end': 593, 'mesh': 'D009599'}, {'text': 'decrease in arterial blood pressure', 'type': 'Disease', 'start': 622, 'end': 657, 'mesh': 'D007022'}, {'text': 'decreased cardiac output', 'type': 'Disease', 'start': 701, 'end': 725, 'mesh': 'D002303'}, {'text': 'Nitroprusside', 'type': 'Chemical', 'start': 737, 'end': 750, 'mesh': 'D009599'}, {'text': 'decreases in arterial blood pressure', 'type': 'Disease', 'start': 770, 'end': 806, 'mesh': 'D007022'}, {'text': 'H2O', 'type': 'Chemical', 'start': 921, 'end': 924, 'mesh': 'D014867'}, {'text': 'nitroprusside', 'type': 'Chemical', 'start': 937, 'end': 950, 'mesh': 'D009599'}, {'text': 'H2O', 'type': 'Chemical', 'start': 1026, 'end': 1029, 'mesh': 'D014867'}, {'text': 'nitroprusside', 'type': 'Chemical', 'start': 1122, 'end': 1135, 'mesh': 'D009599'}, {'text': 'nitroprusside', 'type': 'Chemical', 'start': 1258, 'end': 1271, 'mesh': 'D009599'}, {'text': 'H2O', 'type': 'Chemical', 'start': 1378, 'end': 1381, 'mesh': 'D014867'}]"
+88,869641,Mediation of enhanced reflex vagal bradycardia by L-dopa via central dopamine formation in dogs.,"L-Dopa (5 mg/kg i.v.) decreased blood pressure and heart rate after extracerebral decarboxylase inhibition with MK-486 (25 mg/kg i.v.) in anesthetize MAO-inhibited dogs. In addition, reflex bradycardia caused by injected norepinephrine was significantly enhanced by L-dopa, DL-Threo-dihydroxyphenylserine had no effect on blood pressure, heart rate or reflex responses to norepinephrine. FLA-63, a dopamine-beta-oxidase inhibitor, did not have any effect on the hypotension, bradycardia or reflex-enhancing effect of L-dopa. Pimozide did not affect the actions of L-dopa on blood pressure and heart rate but completely blocked the enhancement of reflexes. Removal of the carotid sinuses caused an elevation blood pressure and heart rate and abolished the negative chronotropic effect of norepinephrine. However, L-dopa restored the bradycardia caused by norepinephrine in addition to decreasing blood pressure and heart rate. 5-HTP (5 mg/kg i.v.) decreased blood pressure and heart rate and decreased the reflex bradycardia to norepinephrine. It is concluded that L-dopa enhances reflex bradycardia through central alpha-receptor stimulation. Furthermore, the effects are mediated through dopamine rather than norepinephrine and do not require the carotid sinus baroreceptors.","[{'text': 'bradycardia', 'type': 'Disease', 'start': 35, 'end': 46, 'mesh': 'D001919'}, {'text': 'L-dopa', 'type': 'Chemical', 'start': 50, 'end': 56, 'mesh': 'D007980'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 69, 'end': 77, 'mesh': 'D004298'}, {'text': 'L-Dopa', 'type': 'Chemical', 'start': 97, 'end': 103, 'mesh': 'D007980'}, {'text': 'MK-486', 'type': 'Chemical', 'start': 209, 'end': 215, 'mesh': 'D002230'}, {'text': 'MAO', 'type': 'Chemical', 'start': 247, 'end': 250, 'mesh': 'D008995'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 287, 'end': 298, 'mesh': 'D001919'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 318, 'end': 332, 'mesh': 'D009638'}, {'text': 'L-dopa', 'type': 'Chemical', 'start': 363, 'end': 369, 'mesh': 'D007980'}, {'text': 'DL-Threo-dihydroxyphenylserine', 'type': 'Chemical', 'start': 371, 'end': 401, 'mesh': 'D015103'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 469, 'end': 483, 'mesh': 'D009638'}, {'text': 'FLA-63', 'type': 'Chemical', 'start': 485, 'end': 491, 'mesh': 'D005406'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 495, 'end': 503, 'mesh': 'D004298'}, {'text': 'hypotension', 'type': 'Disease', 'start': 559, 'end': 570, 'mesh': 'D007022'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 572, 'end': 583, 'mesh': 'D001919'}, {'text': 'L-dopa', 'type': 'Chemical', 'start': 614, 'end': 620, 'mesh': 'D007980'}, {'text': 'Pimozide', 'type': 'Chemical', 'start': 622, 'end': 630, 'mesh': 'D010868'}, {'text': 'L-dopa', 'type': 'Chemical', 'start': 661, 'end': 667, 'mesh': 'D007980'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 884, 'end': 898, 'mesh': 'D009638'}, {'text': 'L-dopa', 'type': 'Chemical', 'start': 909, 'end': 915, 'mesh': 'D007980'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 929, 'end': 940, 'mesh': 'D001919'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 951, 'end': 965, 'mesh': 'D009638'}, {'text': '5-HTP', 'type': 'Chemical', 'start': 1023, 'end': 1028, 'mesh': 'D006916'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 1109, 'end': 1120, 'mesh': 'D001919'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 1124, 'end': 1138, 'mesh': 'D009638'}, {'text': 'L-dopa', 'type': 'Chemical', 'start': 1161, 'end': 1167, 'mesh': 'D007980'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 1184, 'end': 1195, 'mesh': 'D001919'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1286, 'end': 1294, 'mesh': 'D004298'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 1307, 'end': 1321, 'mesh': 'D009638'}]"
+89,1749407,Cocaine-induced myocardial infarction: clinical observations and pathogenetic considerations.,"Clinical and experimental data published to date suggest several possible mechanisms by which cocaine may result in acute myocardial infarction. In individuals with preexisting, high-grade coronary arterial narrowing, acute myocardial infarction may result from an increase in myocardial oxygen demand associated with cocaine-induced increase in rate-pressure product. In other individuals with no underlying atherosclerotic obstruction, coronary occlusion may be due to spasm, thrombus, or both. With regard to spasm, the clinical findings are largely circumstantial, and the locus of cocaine-induced vasoconstriction remains speculative. Although certain clinical and experimental findings support the hypothesis that spasm involves the epicardial, medium-size vessels, other data suggest intramural vasoconstriction. Diffuse intramural vasoconstriction is not consistent with reports of segmental, discrete infarction. Whereas certain in vivo data suggest that these effects are alpha-mediated, other in vitro data suggest the opposite. The finding of cocaine-induced vasoconstriction in segments of (noninnervated) human umbilical artery suggests that the presence or absence of intact innervation is not sufficient to explain the discrepant data involving the possibility of alpha-mediated effects. Finally, the contribution of a primary, thrombotic effect of cocaine has not been excluded.","[{'text': 'Cocaine', 'type': 'Chemical', 'start': 0, 'end': 7, 'mesh': 'D003042'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 16, 'end': 37, 'mesh': 'D009203'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 188, 'end': 195, 'mesh': 'D003042'}, {'text': 'acute myocardial infarction', 'type': 'Disease', 'start': 210, 'end': 237, 'mesh': 'D009203'}, {'text': 'acute myocardial infarction', 'type': 'Disease', 'start': 312, 'end': 339, 'mesh': 'D009203'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 382, 'end': 388, 'mesh': 'D010100'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 412, 'end': 419, 'mesh': 'D003042'}, {'text': 'atherosclerotic obstruction', 'type': 'Disease', 'start': 503, 'end': 530, 'mesh': 'D050197'}, {'text': 'coronary occlusion', 'type': 'Disease', 'start': 532, 'end': 550, 'mesh': 'D054059'}, {'text': 'spasm', 'type': 'Disease', 'start': 565, 'end': 570, 'mesh': 'D013035'}, {'text': 'thrombus', 'type': 'Disease', 'start': 572, 'end': 580, 'mesh': 'D013927'}, {'text': 'spasm', 'type': 'Disease', 'start': 606, 'end': 611, 'mesh': 'D013035'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 680, 'end': 687, 'mesh': 'D003042'}, {'text': 'spasm', 'type': 'Disease', 'start': 814, 'end': 819, 'mesh': 'D013035'}, {'text': 'infarction', 'type': 'Disease', 'start': 1004, 'end': 1014, 'mesh': 'D007238'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1149, 'end': 1156, 'mesh': 'D003042'}, {'text': 'thrombotic', 'type': 'Disease', 'start': 1438, 'end': 1448, 'mesh': 'D013927'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1459, 'end': 1466, 'mesh': 'D003042'}]"
+90,1786266,"Rabbit syndrome, antidepressant use, and cerebral perfusion SPECT scan findings.","The rabbit syndrome is an extrapyramidal side effect associated with chronic neuroleptic therapy. Its occurrence in a patient being treated with imipramine is described, representing the first reported case of this syndrome in conjunction with antidepressants. Repeated cerebral perfusion SPECT scans revealed decreased basal ganglia perfusion while the movement disorder was present, and a return to normal perfusion when the rabbit syndrome resolved.","[{'text': 'Rabbit syndrome', 'type': 'Disease', 'start': 0, 'end': 15, 'mesh': 'D001480'}, {'text': 'antidepressant', 'type': 'Chemical', 'start': 17, 'end': 31, 'mesh': 'D000928'}, {'text': 'rabbit syndrome', 'type': 'Disease', 'start': 85, 'end': 100, 'mesh': 'D001480'}, {'text': 'imipramine', 'type': 'Chemical', 'start': 226, 'end': 236, 'mesh': 'D007099'}, {'text': 'antidepressants', 'type': 'Chemical', 'start': 325, 'end': 340, 'mesh': 'D000928'}, {'text': 'decreased basal ganglia perfusion', 'type': 'Disease', 'start': 391, 'end': 424, 'mesh': 'D001480'}, {'text': 'movement disorder', 'type': 'Disease', 'start': 435, 'end': 452, 'mesh': 'D009069'}, {'text': 'rabbit syndrome', 'type': 'Disease', 'start': 508, 'end': 523, 'mesh': 'D001480'}]"
+91,1835291,Acute bronchodilating effects of ipratropium bromide and theophylline in chronic obstructive pulmonary disease.,"The bronchodilator effects of a single dose of ipratropium bromide aerosol (36 micrograms) and short-acting theophylline tablets (dose titrated to produce serum levels of 10-20 micrograms/mL) were compared in a double-blind, placebo-controlled crossover study in 21 patients with stable, chronic obstructive pulmonary disease. Mean peak forced expiratory volume in 1 second (FEV1) increases over baseline and the proportion of patients attaining at least a 15% increase in the FEV1 (responders) were 31% and 90%, respectively, for ipratropium and 17% and 50%, respectively, for theophylline. The average FEV1 increases during the 6-hour observation period were 18% for ipratropium and 8% for theophylline. The mean duration of action was 3.8 hours with ipratropium and 2.4 hours with theophylline. While side effects were rare, those experienced after theophylline use did involve the cardiovascular and gastrointestinal systems. These results show that ipratropium is a more potent bronchodilator than oral theophylline in patients with chronic airflow obstruction.","[{'text': 'ipratropium bromide', 'type': 'Chemical', 'start': 33, 'end': 52, 'mesh': 'D009241'}, {'text': 'theophylline', 'type': 'Chemical', 'start': 57, 'end': 69, 'mesh': 'D013806'}, {'text': 'chronic obstructive pulmonary disease', 'type': 'Disease', 'start': 73, 'end': 110, 'mesh': 'D029424'}, {'text': 'ipratropium bromide', 'type': 'Chemical', 'start': 159, 'end': 178, 'mesh': 'D009241'}, {'text': 'theophylline', 'type': 'Chemical', 'start': 220, 'end': 232, 'mesh': 'D013806'}, {'text': 'chronic obstructive pulmonary disease', 'type': 'Disease', 'start': 400, 'end': 437, 'mesh': 'D029424'}, {'text': 'ipratropium', 'type': 'Chemical', 'start': 643, 'end': 654, 'mesh': 'D009241'}, {'text': 'theophylline', 'type': 'Chemical', 'start': 690, 'end': 702, 'mesh': 'D013806'}, {'text': 'ipratropium', 'type': 'Chemical', 'start': 781, 'end': 792, 'mesh': 'D009241'}, {'text': 'theophylline', 'type': 'Chemical', 'start': 804, 'end': 816, 'mesh': 'D013806'}, {'text': 'ipratropium', 'type': 'Chemical', 'start': 865, 'end': 876, 'mesh': 'D009241'}, {'text': 'theophylline', 'type': 'Chemical', 'start': 896, 'end': 908, 'mesh': 'D013806'}, {'text': 'theophylline', 'type': 'Chemical', 'start': 964, 'end': 976, 'mesh': 'D013806'}, {'text': 'ipratropium', 'type': 'Chemical', 'start': 1066, 'end': 1077, 'mesh': 'D009241'}, {'text': 'theophylline', 'type': 'Chemical', 'start': 1120, 'end': 1132, 'mesh': 'D013806'}, {'text': 'chronic airflow obstruction', 'type': 'Disease', 'start': 1150, 'end': 1177, 'mesh': 'D029424'}]"
+92,1919871,Irreversible damage to the medullary interstitium in experimental analgesic nephropathy in F344 rats.,"Renal papillary necrosis (RPN) and a decreased urinary concentrating ability developed during continuous long-term treatment with aspirin and paracetamol in female Fischer 344 rats. Renal structure and concentrating ability were examined after a recovery period of up to 18 weeks, when no analgesics were given, to investigate whether the analgesic-induced changes were reversible. There was no evidence of repair to the damaged medullary interstitial matrix, or proliferation of remaining undamaged type 1 medullary interstitial cells after the recovery period following analgesic treatment. The recovery of urinary concentrating ability was related to the length of analgesic treatment and the extent of the resulting inner medullary structural damage. During the early stages of analgesic treatment, the changes in urinary concentrating ability were reversible, but after prolonged analgesic treatment, maximum urinary concentrating ability failed to recover. This study shows that prolonged analgesic treatment in Fischer 344 rats causes progressive and irreversible damage to the interstitial matrix and type 1 interstitial cells leading to RPN. The associated urinary concentrating defect is reversible only during the early stages of structural damage to the inner medulla.","[{'text': 'nephropathy', 'type': 'Disease', 'start': 76, 'end': 87, 'mesh': 'D007674'}, {'text': 'Renal papillary necrosis', 'type': 'Disease', 'start': 102, 'end': 126, 'mesh': 'D007681'}, {'text': 'RPN', 'type': 'Disease', 'start': 128, 'end': 131, 'mesh': 'D007681'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 232, 'end': 239, 'mesh': 'D001241'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 244, 'end': 255, 'mesh': 'D000082'}, {'text': 'RPN', 'type': 'Disease', 'start': 1248, 'end': 1251, 'mesh': 'D007681'}]"
+93,1987816,Less frequent lithium administration and lower urine volume.,"OBJECTIVE: This study was designed to determine whether patients maintained on a regimen of lithium on a once-per-day schedule have lower urine volumes than do patients receiving multiple doses per day. METHOD: This was a cross-sectional study of 85 patients from a lithium clinic who received different dose schedules. Patients were admitted to the hospital for measurement of lithium level, creatinine clearance, urine volume, and maximum osmolality. RESULTS: Multiple daily doses of lithium were associated with higher urine volumes. The dosing schedule, duration of lithium treatment, and daily dose of lithium did not affect maximum osmolality or creatinine clearance. CONCLUSIONS: Urine volume can be reduced by giving lithium once daily and/or by lowering the total daily dose. Lithium-induced polyuria seems to be related to extrarenal as well as to renal effects.","[{'text': 'lithium', 'type': 'Chemical', 'start': 14, 'end': 21, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 153, 'end': 160, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 327, 'end': 334, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 439, 'end': 446, 'mesh': 'D008094'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 454, 'end': 464, 'mesh': 'D003404'}, {'text': 'lithium', 'type': 'Chemical', 'start': 547, 'end': 554, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 631, 'end': 638, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 668, 'end': 675, 'mesh': 'D008094'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 713, 'end': 723, 'mesh': 'D003404'}, {'text': 'lithium', 'type': 'Chemical', 'start': 786, 'end': 793, 'mesh': 'D008094'}, {'text': 'Lithium', 'type': 'Chemical', 'start': 846, 'end': 853, 'mesh': 'D008094'}, {'text': 'polyuria', 'type': 'Disease', 'start': 862, 'end': 870, 'mesh': 'D011141'}]"
+94,2054792,Effect of adriamycin combined with whole body hyperthermia on tumor and normal tissues.,"Thermal enhancement of Adriamycin-mediated antitumor activity and normal tissue toxicities by whole body hyperthermia were compared using a F344 rat model. Antitumor activity was studied using a tumor growth delay assay. Acute normal tissue toxicities (i.e., leukopenia and thrombocytopenia) and late normal tissue toxicities (i.e., myocardial and kidney injury) were evaluated by functional/physiological assays and by morphological techniques. Whole body hyperthermia (120 min at 41.5 degrees C) enhanced both Adriamycin-mediated antitumor activity and toxic side effects. The thermal enhancement ratio calculated for antitumor activity was 1.6. Thermal enhancement ratios estimated for ""acute"" hematological changes were 1.3, whereas those estimated for ""late"" damage (based on morphological cardiac and renal lesions) varied between 2.4 and 4.3. Thus, while whole body hyperthermia enhances Adriamycin-mediated antitumor effect, normal tissue toxicity is also increased, and the potential therapeutic gain of the combined modality treatment is eroded.","[{'text': 'adriamycin', 'type': 'Chemical', 'start': 10, 'end': 20, 'mesh': 'D004317'}, {'text': 'hyperthermia', 'type': 'Disease', 'start': 46, 'end': 58, 'mesh': 'D005334'}, {'text': 'tumor', 'type': 'Disease', 'start': 62, 'end': 67, 'mesh': 'D009369'}, {'text': 'Adriamycin', 'type': 'Chemical', 'start': 111, 'end': 121, 'mesh': 'D004317'}, {'text': 'toxicities', 'type': 'Disease', 'start': 168, 'end': 178, 'mesh': 'D064420'}, {'text': 'hyperthermia', 'type': 'Disease', 'start': 193, 'end': 205, 'mesh': 'D005334'}, {'text': 'tumor', 'type': 'Disease', 'start': 283, 'end': 288, 'mesh': 'D009369'}, {'text': 'toxicities', 'type': 'Disease', 'start': 329, 'end': 339, 'mesh': 'D064420'}, {'text': 'leukopenia', 'type': 'Disease', 'start': 347, 'end': 357, 'mesh': 'D007970'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 362, 'end': 378, 'mesh': 'D013921'}, {'text': 'toxicities', 'type': 'Disease', 'start': 403, 'end': 413, 'mesh': 'D064420'}, {'text': 'hyperthermia', 'type': 'Disease', 'start': 545, 'end': 557, 'mesh': 'D005334'}, {'text': 'Adriamycin', 'type': 'Chemical', 'start': 600, 'end': 610, 'mesh': 'D004317'}, {'text': 'hyperthermia', 'type': 'Disease', 'start': 961, 'end': 973, 'mesh': 'D005334'}, {'text': 'Adriamycin', 'type': 'Chemical', 'start': 983, 'end': 993, 'mesh': 'D004317'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1035, 'end': 1043, 'mesh': 'D064420'}]"
+95,2304736,Prazosin-induced stress incontinence.,"A case of genuine stress incontinence due to prazosin, a common antihypertensive drug, is presented. Prazosin exerts its antihypertensive effects through vasodilatation caused by selective blockade of postsynaptic alpha-1 adrenergic receptors. As an alpha-blocker, it also exerts a significant relaxant effect on the bladder neck and urethra. The patient's clinical course is described and correlated with initial urodynamic studies while on prazosin and subsequent studies while taking verapamil. Her incontinence resolved with the change of medication. The restoration of continence was accompanied by a substantial rise in maximum urethral pressure, maximum urethral closure pressure, and functional urethral length. Patients who present with stress incontinence while taking prazosin should change their antihypertensive medication before considering surgery, because their incontinence may resolve spontaneously with a change in drug therapy.","[{'text': 'Prazosin', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D011224'}, {'text': 'stress incontinence', 'type': 'Disease', 'start': 17, 'end': 36, 'mesh': 'D014550'}, {'text': 'stress incontinence', 'type': 'Disease', 'start': 56, 'end': 75, 'mesh': 'D014550'}, {'text': 'prazosin', 'type': 'Chemical', 'start': 83, 'end': 91, 'mesh': 'D011224'}, {'text': 'Prazosin', 'type': 'Chemical', 'start': 139, 'end': 147, 'mesh': 'D011224'}, {'text': 'prazosin', 'type': 'Chemical', 'start': 480, 'end': 488, 'mesh': 'D011224'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 525, 'end': 534, 'mesh': 'D014700'}, {'text': 'incontinence', 'type': 'Disease', 'start': 540, 'end': 552, 'mesh': 'D014549'}, {'text': 'stress incontinence', 'type': 'Disease', 'start': 784, 'end': 803, 'mesh': 'D014550'}, {'text': 'prazosin', 'type': 'Chemical', 'start': 817, 'end': 825, 'mesh': 'D011224'}, {'text': 'incontinence', 'type': 'Disease', 'start': 916, 'end': 928, 'mesh': 'D014549'}]"
+96,2312209,Myocardial infarction following sublingual administration of isosorbide dinitrate.,"A 78-year-old with healed septal necrosis suffered a recurrent myocardial infarction of the anterior wall following the administration of isosorbide dinitrate 5 mg sublingually. After detailing the course of events, we discuss the role of paradoxical coronary spasm and hypotension-mediated myocardial ischemia occurring downstream to significant coronary arterial stenosis in the pathophysiology of acute coronary insufficiency.","[{'text': 'Myocardial infarction', 'type': 'Disease', 'start': 0, 'end': 21, 'mesh': 'D009203'}, {'text': 'isosorbide dinitrate', 'type': 'Chemical', 'start': 61, 'end': 81, 'mesh': 'D007548'}, {'text': 'necrosis', 'type': 'Disease', 'start': 116, 'end': 124, 'mesh': 'D009336'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 146, 'end': 167, 'mesh': 'D009203'}, {'text': 'isosorbide dinitrate', 'type': 'Chemical', 'start': 221, 'end': 241, 'mesh': 'D007548'}, {'text': 'spasm', 'type': 'Disease', 'start': 343, 'end': 348, 'mesh': 'D013035'}, {'text': 'hypotension', 'type': 'Disease', 'start': 353, 'end': 364, 'mesh': 'D007022'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 374, 'end': 393, 'mesh': 'D017202'}, {'text': 'coronary arterial stenosis', 'type': 'Disease', 'start': 430, 'end': 456, 'mesh': 'D023921'}, {'text': 'acute coronary insufficiency', 'type': 'Disease', 'start': 483, 'end': 511, 'mesh': 'D054058'}]"
+97,2549018,Fluoxetine-induced akathisia: clinical and theoretical implications.,"Five patients receiving fluoxetine for the treatment of obsessive compulsive disorder or major depression developed akathisia. The typical fluoxetine-induced symptoms of restlessness, constant pacing, purposeless movements of the feet and legs, and marked anxiety were indistinguishable from those of neuroleptic-induced akathisia. Three patients who had experienced neuroleptic-induced akathisia in the past reported that the symptoms of fluoxetine-induced akathisia were identical, although somewhat milder. Akathisia appeared to be a common side effect of fluoxetine and generally responded well to treatment with the beta-adrenergic antagonist propranolol, dose reduction, or both. The authors suggest that fluoxetine-induced akathisia may be caused by serotonergically mediated inhibition of dopaminergic neurotransmission and that the pathophysiology of fluoxetine-induced akathisia and tricyclic antidepressant-induced ""jitteriness"" may be identical.","[{'text': 'Fluoxetine', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D005473'}, {'text': 'akathisia', 'type': 'Disease', 'start': 19, 'end': 28, 'mesh': 'D017109'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 93, 'end': 103, 'mesh': 'D005473'}, {'text': 'obsessive compulsive disorder', 'type': 'Disease', 'start': 125, 'end': 154, 'mesh': 'D009771'}, {'text': 'major depression', 'type': 'Disease', 'start': 158, 'end': 174, 'mesh': 'D003865'}, {'text': 'akathisia', 'type': 'Disease', 'start': 185, 'end': 194, 'mesh': 'D017109'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 208, 'end': 218, 'mesh': 'D005473'}, {'text': 'anxiety', 'type': 'Disease', 'start': 325, 'end': 332, 'mesh': 'D001008'}, {'text': 'akathisia', 'type': 'Disease', 'start': 390, 'end': 399, 'mesh': 'D017109'}, {'text': 'akathisia', 'type': 'Disease', 'start': 456, 'end': 465, 'mesh': 'D017109'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 508, 'end': 518, 'mesh': 'D005473'}, {'text': 'akathisia', 'type': 'Disease', 'start': 527, 'end': 536, 'mesh': 'D017109'}, {'text': 'Akathisia', 'type': 'Disease', 'start': 579, 'end': 588, 'mesh': 'D017109'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 628, 'end': 638, 'mesh': 'D005473'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 717, 'end': 728, 'mesh': 'D011433'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 780, 'end': 790, 'mesh': 'D005473'}, {'text': 'akathisia', 'type': 'Disease', 'start': 799, 'end': 808, 'mesh': 'D017109'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 929, 'end': 939, 'mesh': 'D005473'}, {'text': 'akathisia', 'type': 'Disease', 'start': 948, 'end': 957, 'mesh': 'D017109'}, {'text': 'antidepressant', 'type': 'Chemical', 'start': 972, 'end': 986, 'mesh': 'D000928'}]"
+98,2611118,Chronic active hepatitis associated with diclofenac sodium therapy.,"Diclofenac sodium (Voltarol, Geigy Pharmaceuticals) is a non-steroidal anti-inflammatory derivative of phenylacetic acid. Although generally well-tolerated, asymptomatic abnormalities of liver function have been recorded and, less commonly, severe hepatitis induced by diclofenac. The patient described developed chronic active hepatitis after six months therapy with diclofenac sodium which progressed despite the withdrawal of the drug, a finding not previously reported.","[{'text': 'Chronic active hepatitis', 'type': 'Disease', 'start': 0, 'end': 24, 'mesh': 'D006521'}, {'text': 'diclofenac sodium', 'type': 'Chemical', 'start': 41, 'end': 58, 'mesh': 'D004008'}, {'text': 'Diclofenac sodium', 'type': 'Chemical', 'start': 68, 'end': 85, 'mesh': 'D004008'}, {'text': 'Voltarol', 'type': 'Chemical', 'start': 87, 'end': 95, 'mesh': 'D004008'}, {'text': 'phenylacetic acid', 'type': 'Chemical', 'start': 171, 'end': 188, 'mesh': 'C025136'}, {'text': 'abnormalities of liver function', 'type': 'Disease', 'start': 238, 'end': 269, 'mesh': 'D056486'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 316, 'end': 325, 'mesh': 'D056486'}, {'text': 'diclofenac', 'type': 'Chemical', 'start': 337, 'end': 347, 'mesh': 'D004008'}, {'text': 'chronic active hepatitis', 'type': 'Disease', 'start': 381, 'end': 405, 'mesh': 'D006521'}, {'text': 'diclofenac sodium', 'type': 'Chemical', 'start': 436, 'end': 453, 'mesh': 'D004008'}]"
+99,2673163,Stroke associated with cocaine use.,"We describe eight patients in whom cocaine use was related to stroke and review 39 cases from the literature. Among these 47 patients the mean (+/- SD) age was 32.5 +/- 12.1 years; 76% (34/45) were men. Stroke followed cocaine use by inhalation, intranasal, intravenous, and intramuscular routes. Intracranial aneurysms or arteriovenous malformations were present in 17 of 32 patients studied angiographically or at autopsy; cerebral vasculitis was present in two patients. Cerebral infarction occurred in 10 patients (22%), intracerebral hemorrhage in 22 (49%), and subarachnoid hemorrhage in 13 (29%). These data indicate that (1) the apparent incidence of stroke related to cocaine use is increasing; (2) cocaine-associated stroke occurs primarily in young adults; (3) stroke may follow any route of cocaine administration; (4) stroke after cocaine use is frequently associated with intracranial aneurysms and arteriovenous malformations; and (5) in cocaine-associated stroke, the frequency of intracranial hemorrhage exceeds that of cerebral infarction.","[{'text': 'Stroke', 'type': 'Disease', 'start': 0, 'end': 6, 'mesh': 'D020521'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 23, 'end': 30, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 71, 'end': 78, 'mesh': 'D003042'}, {'text': 'stroke', 'type': 'Disease', 'start': 98, 'end': 104, 'mesh': 'D020521'}, {'text': 'Stroke', 'type': 'Disease', 'start': 239, 'end': 245, 'mesh': 'D020521'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 255, 'end': 262, 'mesh': 'D003042'}, {'text': 'Intracranial aneurysms', 'type': 'Disease', 'start': 333, 'end': 355, 'mesh': 'D002532'}, {'text': 'arteriovenous malformations', 'type': 'Disease', 'start': 359, 'end': 386, 'mesh': 'D001165'}, {'text': 'cerebral vasculitis', 'type': 'Disease', 'start': 461, 'end': 480, 'mesh': 'D020293'}, {'text': 'Cerebral infarction', 'type': 'Disease', 'start': 510, 'end': 529, 'mesh': 'D002544'}, {'text': 'intracerebral hemorrhage', 'type': 'Disease', 'start': 561, 'end': 585, 'mesh': 'D002543'}, {'text': 'subarachnoid hemorrhage', 'type': 'Disease', 'start': 603, 'end': 626, 'mesh': 'D013345'}, {'text': 'stroke', 'type': 'Disease', 'start': 695, 'end': 701, 'mesh': 'D020521'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 713, 'end': 720, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 744, 'end': 751, 'mesh': 'D003042'}, {'text': 'stroke', 'type': 'Disease', 'start': 763, 'end': 769, 'mesh': 'D020521'}, {'text': 'stroke', 'type': 'Disease', 'start': 808, 'end': 814, 'mesh': 'D020521'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 839, 'end': 846, 'mesh': 'D003042'}, {'text': 'stroke', 'type': 'Disease', 'start': 867, 'end': 873, 'mesh': 'D020521'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 880, 'end': 887, 'mesh': 'D003042'}, {'text': 'intracranial aneurysms', 'type': 'Disease', 'start': 922, 'end': 944, 'mesh': 'D002532'}, {'text': 'arteriovenous malformations', 'type': 'Disease', 'start': 949, 'end': 976, 'mesh': 'D001165'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 989, 'end': 996, 'mesh': 'D003042'}, {'text': 'stroke', 'type': 'Disease', 'start': 1008, 'end': 1014, 'mesh': 'D020521'}, {'text': 'intracranial hemorrhage', 'type': 'Disease', 'start': 1033, 'end': 1056, 'mesh': 'D020300'}, {'text': 'cerebral infarction', 'type': 'Disease', 'start': 1073, 'end': 1092, 'mesh': 'D002544'}]"
+100,3107448,Glyburide-induced hepatitis.,"Drug-induced hepatotoxicity, although common, has been reported only infrequently with sulfonylureas. For glyburide, a second-generation sulfonylurea, only two brief reports of hepatotoxicity exist. Two patients with type II diabetes mellitus developed an acute hepatitis-like syndrome soon after initiation of glyburide therapy. There was no serologic evidence of viral infection, and a liver biopsy sample showed a histologic pattern consistent with drug-induced hepatitis. Both patients recovered quickly after stopping glyburide therapy and have remained well for a follow-up period of 1 year. Glyburide can produce an acute hepatitis-like illness in some persons.","[{'text': 'Glyburide', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D005905'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 18, 'end': 27, 'mesh': 'D056486'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 42, 'end': 56, 'mesh': 'D056486'}, {'text': 'sulfonylureas', 'type': 'Chemical', 'start': 116, 'end': 129, 'mesh': 'D013453'}, {'text': 'glyburide', 'type': 'Chemical', 'start': 135, 'end': 144, 'mesh': 'D005905'}, {'text': 'sulfonylurea', 'type': 'Chemical', 'start': 166, 'end': 178, 'mesh': 'D013453'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 206, 'end': 220, 'mesh': 'D056486'}, {'text': 'type II diabetes mellitus', 'type': 'Disease', 'start': 246, 'end': 271, 'mesh': 'D003924'}, {'text': 'acute hepatitis-like syndrome', 'type': 'Disease', 'start': 285, 'end': 314, 'mesh': 'D056486'}, {'text': 'glyburide', 'type': 'Chemical', 'start': 340, 'end': 349, 'mesh': 'D005905'}, {'text': 'viral infection', 'type': 'Disease', 'start': 394, 'end': 409, 'mesh': 'D014777'}, {'text': 'drug-induced hepatitis', 'type': 'Disease', 'start': 481, 'end': 503, 'mesh': 'D056486'}, {'text': 'glyburide', 'type': 'Chemical', 'start': 552, 'end': 561, 'mesh': 'D005905'}, {'text': 'Glyburide', 'type': 'Chemical', 'start': 627, 'end': 636, 'mesh': 'D005905'}, {'text': 'acute hepatitis-like illness', 'type': 'Disease', 'start': 652, 'end': 680, 'mesh': 'D056486'}]"
+101,3341566,Systolic pressure variation is greater during hemorrhage than during sodium nitroprusside-induced hypotension in ventilated dogs.,"The systolic pressure variation (SPV), which is the difference between the maximal and minimal values of the systolic blood pressure (SBP) after one positive-pressure breath, was studied in ventilated dogs subjected to hypotension. Mean arterial pressure was decreased to 50 mm Hg for 30 minutes either by hemorrhage (HEM, n = 7) or by continuous infusion of sodium nitroprusside (SNP, n = 7). During HEM-induced hypotension the cardiac output was significantly lower and systemic vascular resistance higher compared with that in the SNP group. The systemic, central venous, pulmonary capillary wedge pressures, and heart rates, were similar in the two groups. Analysis of the respiratory changes in the arterial pressure waveform enabled differentiation between the two groups. The SPV during hypotension was 15.7 +/- 6.7 mm Hg in the HEM group, compared with 9.1 +/- 2.0 mm Hg in the SNP group (P less than 0.02). The delta down, which is the measure of decrease of SBP after a mechanical breath, was 20.3 +/- 8.4 and 10.1 +/- 3.8 mm Hg in the HEM and SNP groups, respectively, during hypotension (P less than 0.02). It is concluded that increases in the SPV and the delta down are characteristic of a hypotensive state due to a predominant decrease in preload. They are thus more important during absolute hypovolemia than during deliberate hypotension.","[{'text': 'hemorrhage', 'type': 'Disease', 'start': 46, 'end': 56, 'mesh': 'D006470'}, {'text': 'sodium nitroprusside', 'type': 'Chemical', 'start': 69, 'end': 89, 'mesh': 'D009599'}, {'text': 'hypotension', 'type': 'Disease', 'start': 98, 'end': 109, 'mesh': 'D007022'}, {'text': 'hypotension', 'type': 'Disease', 'start': 349, 'end': 360, 'mesh': 'D007022'}, {'text': 'hemorrhage', 'type': 'Disease', 'start': 436, 'end': 446, 'mesh': 'D006470'}, {'text': 'HEM', 'type': 'Disease', 'start': 448, 'end': 451, 'mesh': 'D006470'}, {'text': 'sodium nitroprusside', 'type': 'Chemical', 'start': 489, 'end': 509, 'mesh': 'D009599'}, {'text': 'SNP', 'type': 'Chemical', 'start': 511, 'end': 514, 'mesh': 'D009599'}, {'text': 'HEM', 'type': 'Disease', 'start': 531, 'end': 534, 'mesh': 'D006470'}, {'text': 'hypotension', 'type': 'Disease', 'start': 543, 'end': 554, 'mesh': 'D007022'}, {'text': 'SNP', 'type': 'Chemical', 'start': 664, 'end': 667, 'mesh': 'D009599'}, {'text': 'hypotension', 'type': 'Disease', 'start': 924, 'end': 935, 'mesh': 'D007022'}, {'text': 'HEM', 'type': 'Disease', 'start': 966, 'end': 969, 'mesh': 'D006470'}, {'text': 'SNP', 'type': 'Chemical', 'start': 1016, 'end': 1019, 'mesh': 'D009599'}, {'text': 'HEM', 'type': 'Disease', 'start': 1176, 'end': 1179, 'mesh': 'D006470'}, {'text': 'SNP', 'type': 'Chemical', 'start': 1184, 'end': 1187, 'mesh': 'D009599'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1217, 'end': 1228, 'mesh': 'D007022'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 1334, 'end': 1345, 'mesh': 'D007022'}, {'text': 'hypovolemia', 'type': 'Disease', 'start': 1439, 'end': 1450, 'mesh': 'D020896'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1474, 'end': 1485, 'mesh': 'D007022'}]"
+102,3564823,Drug-induced arterial spasm relieved by lidocaine. Case report.,"Following major intracranial surgery in a 35-year-old man, sodium pentothal was intravenously infused to minimize cerebral ischaemia. Intense vasospasm with threatened gangrene arose in the arm used for the infusion. Since the cranial condition precluded use of more usual methods, lidocaine was given intra-arterially, with careful cardiovascular monitoring, to counteract the vasospasm. The treatment was rapidly successful.","[{'text': 'spasm', 'type': 'Disease', 'start': 22, 'end': 27, 'mesh': 'D013035'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 40, 'end': 49, 'mesh': 'D008012'}, {'text': 'sodium pentothal', 'type': 'Chemical', 'start': 123, 'end': 139, 'mesh': 'D013874'}, {'text': 'cerebral ischaemia', 'type': 'Disease', 'start': 178, 'end': 196, 'mesh': 'D002545'}, {'text': 'vasospasm', 'type': 'Disease', 'start': 206, 'end': 215, 'mesh': 'D020301'}, {'text': 'gangrene', 'type': 'Disease', 'start': 232, 'end': 240, 'mesh': 'D005734'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 346, 'end': 355, 'mesh': 'D008012'}, {'text': 'vasospasm', 'type': 'Disease', 'start': 442, 'end': 451, 'mesh': 'D020301'}]"
+103,3676049,Cerebral blood flow and metabolism during isoflurane-induced hypotension in patients subjected to surgery for cerebral aneurysms.,"Cerebral blood flow and cerebral metabolic rate for oxygen were measured during isoflurane-induced hypotension in 10 patients subjected to craniotomy for clipping of a cerebral aneurysm. Flow and metabolism were measured 5-13 days after the subarachnoid haemorrhage by a modification of the classical Kety-Schmidt technique using xenon-133 i.v. Anaesthesia was maintained with an inspired isoflurane concentration of 0.75% (plus 67% nitrous oxide in oxygen), during which CBF and CMRO2 were 34.3 +/- 2.1 ml/100 g min-1 and 2.32 +/- 0.16 ml/100 g min-1 at PaCO2 4.1 +/- 0.1 kPa (mean +/- SEM). Controlled hypotension to an average MAP of 50-55 mm Hg was induced by increasing the dose of isoflurane, and maintained at an inspired concentration of 2.2 +/- 0.2%. This resulted in a significant decrease in CMRO2 (to 1.73 +/- 0.16 ml/100 g min-1), while CBF was unchanged. After the clipping of the aneurysm the isoflurane concentration was reduced to 0.75%. There was a significant increase in CBF, although CMRO2 was unchanged, compared with pre-hypotensive values. These changes might offer protection to brain tissue during periods of induced hypotension.","[{'text': 'isoflurane', 'type': 'Chemical', 'start': 42, 'end': 52, 'mesh': 'D007530'}, {'text': 'hypotension', 'type': 'Disease', 'start': 61, 'end': 72, 'mesh': 'D007022'}, {'text': 'cerebral aneurysms', 'type': 'Disease', 'start': 110, 'end': 128, 'mesh': 'D002532'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 182, 'end': 188, 'mesh': 'D010100'}, {'text': 'isoflurane', 'type': 'Chemical', 'start': 210, 'end': 220, 'mesh': 'D007530'}, {'text': 'hypotension', 'type': 'Disease', 'start': 229, 'end': 240, 'mesh': 'D007022'}, {'text': 'cerebral aneurysm', 'type': 'Disease', 'start': 298, 'end': 315, 'mesh': 'D002532'}, {'text': 'subarachnoid haemorrhage', 'type': 'Disease', 'start': 371, 'end': 395, 'mesh': 'D013345'}, {'text': 'xenon', 'type': 'Chemical', 'start': 460, 'end': 465, 'mesh': 'D014978'}, {'text': 'isoflurane', 'type': 'Chemical', 'start': 519, 'end': 529, 'mesh': 'D007530'}, {'text': 'nitrous oxide', 'type': 'Chemical', 'start': 563, 'end': 576, 'mesh': 'D009609'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 580, 'end': 586, 'mesh': 'D010100'}, {'text': 'hypotension', 'type': 'Disease', 'start': 734, 'end': 745, 'mesh': 'D007022'}, {'text': 'Hg', 'type': 'Chemical', 'start': 776, 'end': 778, 'mesh': 'D008628'}, {'text': 'isoflurane', 'type': 'Chemical', 'start': 817, 'end': 827, 'mesh': 'D007530'}, {'text': 'aneurysm', 'type': 'Disease', 'start': 1025, 'end': 1033, 'mesh': 'D000783'}, {'text': 'isoflurane', 'type': 'Chemical', 'start': 1038, 'end': 1048, 'mesh': 'D007530'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 1174, 'end': 1185, 'mesh': 'D007022'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1273, 'end': 1284, 'mesh': 'D007022'}]"
+104,3719553,Allergic reaction to 5-fluorouracil infusion.,"An allergic reaction consisting of angioneurotic edema secondary to continuous infusion 5-fluorouracil occurred in a patient with recurrent carcinoma of the oral cavity, cirrhosis, and cisplatin-induced impaired renal function. This reaction occurred during the sixth and seventh courses of infusional chemotherapy. Oral diphenhydramine and prednisone were ineffective in preventing the recurrence of the allergic reaction. Discontinuance of effective chemotherapy in this patient during partial remission resulted in fatal disease progression.","[{'text': 'Allergic reaction', 'type': 'Disease', 'start': 0, 'end': 17, 'mesh': 'D004342'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 21, 'end': 35, 'mesh': 'D005472'}, {'text': 'allergic reaction', 'type': 'Disease', 'start': 49, 'end': 66, 'mesh': 'D004342'}, {'text': 'angioneurotic edema', 'type': 'Disease', 'start': 81, 'end': 100, 'mesh': 'D000799'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 134, 'end': 148, 'mesh': 'D005472'}, {'text': 'carcinoma of the oral cavity', 'type': 'Disease', 'start': 186, 'end': 214, 'mesh': 'D009062'}, {'text': 'cirrhosis', 'type': 'Disease', 'start': 216, 'end': 225, 'mesh': 'D005355'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 231, 'end': 240, 'mesh': 'D002945'}, {'text': 'impaired renal function', 'type': 'Disease', 'start': 249, 'end': 272, 'mesh': 'D007674'}, {'text': 'diphenhydramine', 'type': 'Chemical', 'start': 367, 'end': 382, 'mesh': 'D004155'}, {'text': 'prednisone', 'type': 'Chemical', 'start': 387, 'end': 397, 'mesh': 'D011241'}, {'text': 'allergic reaction', 'type': 'Disease', 'start': 451, 'end': 468, 'mesh': 'D004342'}]"
+105,4008111,Amiodarone-induced sinoatrial block.,"We observed sinoatrial block due to chronic amiodarone administration in a 5-year-old boy with primary cardiomyopathy, Wolff-Parkinson-White syndrome and supraventricular tachycardia. Reduction in the dosage of amiodarone resulted in the disappearance of the sinoatrial block and the persistence of asymptomatic sinus bradycardia.","[{'text': 'Amiodarone', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D000638'}, {'text': 'sinoatrial block', 'type': 'Disease', 'start': 19, 'end': 35, 'mesh': 'D012848'}, {'text': 'sinoatrial block', 'type': 'Disease', 'start': 49, 'end': 65, 'mesh': 'D012848'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 81, 'end': 91, 'mesh': 'D000638'}, {'text': 'primary cardiomyopathy', 'type': 'Disease', 'start': 132, 'end': 154, 'mesh': 'D009202'}, {'text': 'Wolff-Parkinson-White syndrome', 'type': 'Disease', 'start': 156, 'end': 186, 'mesh': 'D014927'}, {'text': 'supraventricular tachycardia', 'type': 'Disease', 'start': 191, 'end': 219, 'mesh': 'D013617'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 248, 'end': 258, 'mesh': 'D000638'}, {'text': 'sinoatrial block', 'type': 'Disease', 'start': 296, 'end': 312, 'mesh': 'D012848'}, {'text': 'sinus bradycardia', 'type': 'Disease', 'start': 349, 'end': 366, 'mesh': 'D012804'}]"
+106,6133211,Possible teratogenicity of sulphasalazine.,"Three infants, born of two mothers with inflammatory bowel disease who received treatment with sulphasalazine throughout pregnancy, were found to have major congenital anomalies. In the singleton pregnancy, the mother had ulcerative colitis, and the infant, a male, had coarctation of the aorta and a ventricular septal defect. In the twin pregnancy, the mother had Crohn's disease. The first twin, a female, had a left Potter-type IIa polycystic kidney and a rudimentary left uterine cornu. The second twin, a male, had some features of Potter's facies, hypoplastic lungs, absent kidneys and ureters, and talipes equinovarus. Despite reports to the contrary, it is suggested that sulphasalazine may be teratogenic.","[{'text': 'sulphasalazine', 'type': 'Chemical', 'start': 27, 'end': 41, 'mesh': 'D012460'}, {'text': 'inflammatory bowel disease', 'type': 'Disease', 'start': 83, 'end': 109, 'mesh': 'D015212'}, {'text': 'sulphasalazine', 'type': 'Chemical', 'start': 138, 'end': 152, 'mesh': 'D012460'}, {'text': 'congenital anomalies', 'type': 'Disease', 'start': 200, 'end': 220, 'mesh': 'D000013'}, {'text': 'ulcerative colitis', 'type': 'Disease', 'start': 265, 'end': 283, 'mesh': 'D003093'}, {'text': 'coarctation of the aorta', 'type': 'Disease', 'start': 313, 'end': 337, 'mesh': 'D001017'}, {'text': 'ventricular septal defect', 'type': 'Disease', 'start': 344, 'end': 369, 'mesh': 'D006345'}, {'text': ""Crohn's disease"", 'type': 'Disease', 'start': 409, 'end': 424, 'mesh': 'D003424'}, {'text': 'Potter-type IIa polycystic kidney', 'type': 'Disease', 'start': 463, 'end': 496, 'mesh': 'D007690'}, {'text': 'rudimentary left uterine cornu', 'type': 'Disease', 'start': 503, 'end': 533, 'mesh': '-1'}, {'text': ""Potter's facies"", 'type': 'Disease', 'start': 581, 'end': 596, 'mesh': '-1'}, {'text': 'hypoplastic lungs', 'type': 'Disease', 'start': 598, 'end': 615, 'mesh': '-1'}, {'text': 'absent kidneys and ureters', 'type': 'Disease', 'start': 617, 'end': 643, 'mesh': '-1'}, {'text': 'talipes equinovarus', 'type': 'Disease', 'start': 649, 'end': 668, 'mesh': 'D003025'}, {'text': 'sulphasalazine', 'type': 'Chemical', 'start': 724, 'end': 738, 'mesh': 'D012460'}]"
+107,6503301,Veno-occlusive liver disease after dacarbazine therapy (DTIC) for melanoma.,A case of veno-occlusive disease of the liver with fatal outcome after dacarbazine (DTIC) therapy for melanoma is reported. There was a fulminant clinical course from start of symptoms until death. At autopsy the liver was enlarged and firm with signs of venous congestion. Small- and medium-sized hepatic veins were blocked by thrombosis. Eosinophilic infiltrations were found around the vessels. Published cases from the literature are reviewed and pertinent features discussed.,"[{'text': 'Veno-occlusive liver disease', 'type': 'Disease', 'start': 0, 'end': 28, 'mesh': 'D006504'}, {'text': 'dacarbazine', 'type': 'Chemical', 'start': 35, 'end': 46, 'mesh': 'D003606'}, {'text': 'DTIC', 'type': 'Chemical', 'start': 56, 'end': 60, 'mesh': 'D003606'}, {'text': 'melanoma', 'type': 'Disease', 'start': 66, 'end': 74, 'mesh': 'D008545'}, {'text': 'veno-occlusive disease of the liver', 'type': 'Disease', 'start': 86, 'end': 121, 'mesh': 'D006504'}, {'text': 'dacarbazine', 'type': 'Chemical', 'start': 147, 'end': 158, 'mesh': 'D003606'}, {'text': 'DTIC', 'type': 'Chemical', 'start': 160, 'end': 164, 'mesh': 'D003606'}, {'text': 'melanoma', 'type': 'Disease', 'start': 178, 'end': 186, 'mesh': 'D008545'}, {'text': 'death', 'type': 'Disease', 'start': 267, 'end': 272, 'mesh': 'D003643'}, {'text': 'venous congestion', 'type': 'Disease', 'start': 331, 'end': 348, 'mesh': 'D006940'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 404, 'end': 414, 'mesh': 'D013927'}]"
+108,6727060,A case of tardive dyskinesia caused by metoclopramide.,"Abnormal involuntary movements appeared in the mouth, tongue, neck and abdomen of a 64-year-old male patient after he took metoclopramide for gastrointestinal disorder in a regimen of 30 mg per day for a total of about 260 days. The symptoms exacerbated to a maximum in a month. When the metoclopramide administration was discontinued, the abnormal movements gradually improved to a considerable extent. Attention to the possible induction of specific tardive dyskinesia is called for in the use of this drug.","[{'text': 'tardive dyskinesia', 'type': 'Disease', 'start': 10, 'end': 28, 'mesh': 'D004409'}, {'text': 'metoclopramide', 'type': 'Chemical', 'start': 39, 'end': 53, 'mesh': 'D008787'}, {'text': 'Abnormal involuntary movements', 'type': 'Disease', 'start': 55, 'end': 85, 'mesh': 'D004409'}, {'text': 'metoclopramide', 'type': 'Chemical', 'start': 178, 'end': 192, 'mesh': 'D008787'}, {'text': 'gastrointestinal disorder', 'type': 'Disease', 'start': 197, 'end': 222, 'mesh': 'D005767'}, {'text': 'metoclopramide', 'type': 'Chemical', 'start': 343, 'end': 357, 'mesh': 'D008787'}, {'text': 'abnormal movements', 'type': 'Disease', 'start': 395, 'end': 413, 'mesh': 'D004409'}, {'text': 'tardive dyskinesia', 'type': 'Disease', 'start': 507, 'end': 525, 'mesh': 'D004409'}]"
+109,7083920,Further observations on the electrophysiologic effects of oral amiodarone therapy.,"A case is presented of a reversible intra-Hisian block occurring under amiodarone treatment for atrial tachycardia in a patient without clear intraventricular conduction abnormalities. His bundle recordings showed an atrial tachycardia with intermittent exit block and greatly prolonged BH and HV intervals (40 and 100 msec, respectively). Thirty days after amiodarone discontinuation, His bundle electrograms showed atrial flutter without intra-Hisian or infra-Hisian delay. Amiodarone should be used with caution during long-term oral therapy in patients with or without clear intraventricular conduction defects.","[{'text': 'amiodarone', 'type': 'Chemical', 'start': 63, 'end': 73, 'mesh': 'D000638'}, {'text': 'intra-Hisian block', 'type': 'Disease', 'start': 119, 'end': 137, 'mesh': 'D006327'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 154, 'end': 164, 'mesh': 'D000638'}, {'text': 'atrial tachycardia', 'type': 'Disease', 'start': 179, 'end': 197, 'mesh': 'D013617'}, {'text': 'intraventricular conduction abnormalities', 'type': 'Disease', 'start': 225, 'end': 266, 'mesh': 'D006345'}, {'text': 'atrial tachycardia', 'type': 'Disease', 'start': 300, 'end': 318, 'mesh': 'D013617'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 441, 'end': 451, 'mesh': 'D000638'}, {'text': 'atrial flutter', 'type': 'Disease', 'start': 500, 'end': 514, 'mesh': 'D001282'}, {'text': 'Amiodarone', 'type': 'Chemical', 'start': 559, 'end': 569, 'mesh': 'D000638'}]"
+110,7269015,Busulfan-induced hemorrhagic cystitis.,"A case of a busulfan-induced hemorrhage cystitis is reported. Spontaneous resolution occurred following cessation of the drug. The similarity between the histologic appearances of busulfan cystitis and both radiation and cyclophosphamide-induced cystitis is discussed and the world literature reviewed. In view of the known tendency of busulfan to induce cellular atypia and carcinoma in other sites, periodic urinary cytology is suggested in patients on long-term therapy.","[{'text': 'Busulfan', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D002066'}, {'text': 'busulfan', 'type': 'Chemical', 'start': 51, 'end': 59, 'mesh': 'D002066'}, {'text': 'busulfan', 'type': 'Chemical', 'start': 219, 'end': 227, 'mesh': 'D002066'}, {'text': 'cystitis', 'type': 'Disease', 'start': 228, 'end': 236, 'mesh': 'D003556'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 260, 'end': 276, 'mesh': 'D003520'}, {'text': 'cystitis', 'type': 'Disease', 'start': 285, 'end': 293, 'mesh': 'D003556'}, {'text': 'busulfan', 'type': 'Chemical', 'start': 375, 'end': 383, 'mesh': 'D002066'}, {'text': 'carcinoma', 'type': 'Disease', 'start': 414, 'end': 423, 'mesh': 'D002277'}]"
+111,7352670,Rebound hypertensive after sodium nitroprusside prevented by saralasin in rats.,"The role of the renin--angiotensin system in the maintenance of blood pressure during halothane anesthesia and sodium nitroprusside (SNP)-induced hypotension was evaluated. Control rats received halothane anesthesia (1 MAC) for one hour, followed by SNP infusion, 40 microgram/kg/min, for 30 min, followed by a 30-min recovery period. A second group of rats was treated identically and, in addition, received an infusion of saralasin (a competitive inhibitor of angiotensin II) throughout the experimental period. In each group, SNP infusion resulted in an initial decrease in blood pressure from 86 torr and 83 torr, respectively, to 48 torr. During the SNP infusion the control animals demonstrated a progressive increase in blood pressure to 61 torr, whereas the saralasin-treated animals showed no change. Following discontinuation of SNP, blood pressure in the control animals rebounded to 94 torr, as compared with 78 torr in the saralasin-treated rats. This study indicates that with stable halothane anesthesia, the partial recovery of blood pressure during SNP infusion and the post-SNP rebound of blood pressure can be completely blocked by saralasin. This demonstrates the participation of the renin--angiotensin system in antagonizing the combined hypotensive effects of halothane and SNP.","[{'text': 'hypertensive', 'type': 'Disease', 'start': 8, 'end': 20, 'mesh': 'D006973'}, {'text': 'sodium nitroprusside', 'type': 'Chemical', 'start': 27, 'end': 47, 'mesh': 'D009599'}, {'text': 'saralasin', 'type': 'Chemical', 'start': 61, 'end': 70, 'mesh': 'D012504'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 103, 'end': 114, 'mesh': 'D000809'}, {'text': 'halothane', 'type': 'Chemical', 'start': 166, 'end': 175, 'mesh': 'D006221'}, {'text': 'sodium nitroprusside', 'type': 'Chemical', 'start': 191, 'end': 211, 'mesh': 'D009599'}, {'text': 'SNP', 'type': 'Chemical', 'start': 213, 'end': 216, 'mesh': 'D009599'}, {'text': 'hypotension', 'type': 'Disease', 'start': 226, 'end': 237, 'mesh': 'D007022'}, {'text': 'halothane', 'type': 'Chemical', 'start': 275, 'end': 284, 'mesh': 'D006221'}, {'text': 'SNP', 'type': 'Chemical', 'start': 330, 'end': 333, 'mesh': 'D009599'}, {'text': 'saralasin', 'type': 'Chemical', 'start': 504, 'end': 513, 'mesh': 'D012504'}, {'text': 'angiotensin II', 'type': 'Chemical', 'start': 542, 'end': 556, 'mesh': 'D000804'}, {'text': 'SNP', 'type': 'Chemical', 'start': 609, 'end': 612, 'mesh': 'D009599'}, {'text': 'SNP', 'type': 'Chemical', 'start': 735, 'end': 738, 'mesh': 'D009599'}, {'text': 'increase in blood pressure', 'type': 'Disease', 'start': 795, 'end': 821, 'mesh': 'D006973'}, {'text': 'saralasin', 'type': 'Chemical', 'start': 846, 'end': 855, 'mesh': 'D012504'}, {'text': 'SNP', 'type': 'Chemical', 'start': 919, 'end': 922, 'mesh': 'D009599'}, {'text': 'saralasin', 'type': 'Chemical', 'start': 1016, 'end': 1025, 'mesh': 'D012504'}, {'text': 'halothane', 'type': 'Chemical', 'start': 1078, 'end': 1087, 'mesh': 'D006221'}, {'text': 'SNP', 'type': 'Chemical', 'start': 1146, 'end': 1149, 'mesh': 'D009599'}, {'text': 'SNP', 'type': 'Chemical', 'start': 1172, 'end': 1175, 'mesh': 'D009599'}, {'text': 'saralasin', 'type': 'Chemical', 'start': 1231, 'end': 1240, 'mesh': 'D012504'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 1292, 'end': 1303, 'mesh': 'D000809'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 1340, 'end': 1351, 'mesh': 'D007022'}, {'text': 'halothane', 'type': 'Chemical', 'start': 1363, 'end': 1372, 'mesh': 'D006221'}, {'text': 'SNP', 'type': 'Chemical', 'start': 1377, 'end': 1380, 'mesh': 'D009599'}]"
+112,7504976,Toxic hepatitis induced by antithyroid drugs: four cases including one with cross-reactivity between carbimazole and benzylthiouracil.,"OBJECTIVE: This study was conducted to assess the occurrence of hepatic adverse effects encountered with antithyroid drugs. METHODS: Retrospective review of medical records of 236 patients with hyperthyroidism admitted in our department (in- or out-patients) from 1986 to 1992. RESULTS: Four patients (1.7%) were identified with toxic hepatitis which could reasonably be attributed to the use of antithyroid agent. Two patients had a cholestatic hepatitis induced by carbimazole (N  omercazole). Two others had a mixed (cholestatic and cytolytic) hepatitis following carbimazole. One of the latter two patients further experienced a cytolytic hepatitis which appeared after Benzylthiouracil (Basd  ne) had replaced carbimazole. Biological features of hepatitis disappeared in all cases after cessation of the incriminated drug, while biliary, viral and immunological searches were negative. Only 2 patients of our retrospective study experienced a mild or severe neutropenia. CONCLUSION: Toxic hepatitis is a potential adverse effect of antithyroid drugs which warrants, as for haematological disturbances, a pre-therapeutic determination and a careful follow-up of relevant biological markers. Moreover, hepatotoxicity may not be restricted to one class of antithyroid agents.","[{'text': 'Toxic hepatitis', 'type': 'Disease', 'start': 0, 'end': 15, 'mesh': 'D056486'}, {'text': 'carbimazole', 'type': 'Chemical', 'start': 101, 'end': 112, 'mesh': 'D002231'}, {'text': 'benzylthiouracil', 'type': 'Chemical', 'start': 117, 'end': 133, 'mesh': 'C019269'}, {'text': 'hepatic adverse effects', 'type': 'Disease', 'start': 199, 'end': 222, 'mesh': 'D056486'}, {'text': 'hyperthyroidism', 'type': 'Disease', 'start': 329, 'end': 344, 'mesh': 'D006980'}, {'text': 'toxic hepatitis', 'type': 'Disease', 'start': 464, 'end': 479, 'mesh': 'D056486'}, {'text': 'carbimazole', 'type': 'Chemical', 'start': 602, 'end': 613, 'mesh': 'D002231'}, {'text': 'N  omercazole', 'type': 'Chemical', 'start': 615, 'end': 628, 'mesh': 'D002231'}, {'text': 'cholestatic', 'type': 'Disease', 'start': 655, 'end': 666, 'mesh': 'D002779'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 682, 'end': 691, 'mesh': 'D056486'}, {'text': 'carbimazole', 'type': 'Chemical', 'start': 702, 'end': 713, 'mesh': 'D002231'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 778, 'end': 787, 'mesh': 'D056486'}, {'text': 'Benzylthiouracil', 'type': 'Chemical', 'start': 809, 'end': 825, 'mesh': 'C019269'}, {'text': 'Basd  ne', 'type': 'Chemical', 'start': 827, 'end': 835, 'mesh': 'C019269'}, {'text': 'carbimazole', 'type': 'Chemical', 'start': 850, 'end': 861, 'mesh': 'D002231'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 886, 'end': 895, 'mesh': 'D056486'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 1098, 'end': 1109, 'mesh': 'D009503'}, {'text': 'Toxic hepatitis', 'type': 'Disease', 'start': 1123, 'end': 1138, 'mesh': 'D056486'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 1340, 'end': 1354, 'mesh': 'D056486'}]"
+113,7628595,Study of the role of vitamin B12 and folinic acid supplementation in preventing hematologic toxicity of zidovudine.,"A prospective, randomized study was conducted to evaluate the role of vitamin B12 and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts < 500/mm3 were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B12 (1000 micrograms monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B12 and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000/mm3 and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B12 or folate levels and development of myelosuppression. Vitamin B12 and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded.","[{'text': 'vitamin B12', 'type': 'Chemical', 'start': 21, 'end': 32, 'mesh': 'D014805'}, {'text': 'folinic acid', 'type': 'Chemical', 'start': 37, 'end': 49, 'mesh': 'D002955'}, {'text': 'toxicity', 'type': 'Disease', 'start': 92, 'end': 100, 'mesh': 'D064420'}, {'text': 'zidovudine', 'type': 'Chemical', 'start': 104, 'end': 114, 'mesh': 'D015215'}, {'text': 'vitamin B12', 'type': 'Chemical', 'start': 186, 'end': 197, 'mesh': 'D014805'}, {'text': 'folinic acid', 'type': 'Chemical', 'start': 202, 'end': 214, 'mesh': 'D002955'}, {'text': 'zidovudine', 'type': 'Chemical', 'start': 245, 'end': 255, 'mesh': 'D015215'}, {'text': 'ZDV', 'type': 'Chemical', 'start': 257, 'end': 260, 'mesh': 'D015215'}, {'text': 'bone marrow suppression', 'type': 'Disease', 'start': 270, 'end': 293, 'mesh': 'D001855'}, {'text': 'human immunodeficiency virus (HIV)-infected', 'type': 'Disease', 'start': 308, 'end': 351, 'mesh': 'D015658'}, {'text': 'ZDV', 'type': 'Chemical', 'start': 427, 'end': 430, 'mesh': 'D015215'}, {'text': 'folinic acid', 'type': 'Chemical', 'start': 493, 'end': 505, 'mesh': 'D002955'}, {'text': 'vitamin B12', 'type': 'Chemical', 'start': 538, 'end': 549, 'mesh': 'D014805'}, {'text': 'death', 'type': 'Disease', 'start': 665, 'end': 670, 'mesh': 'D003643'}, {'text': 'vitamin B12', 'type': 'Chemical', 'start': 842, 'end': 853, 'mesh': 'D014805'}, {'text': 'folate', 'type': 'Chemical', 'start': 858, 'end': 864, 'mesh': 'D005492'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1117, 'end': 1125, 'mesh': 'D064420'}, {'text': 'vitamin B12', 'type': 'Chemical', 'start': 1287, 'end': 1298, 'mesh': 'D014805'}, {'text': 'folate', 'type': 'Chemical', 'start': 1302, 'end': 1308, 'mesh': 'D005492'}, {'text': 'myelosuppression', 'type': 'Disease', 'start': 1335, 'end': 1351, 'mesh': 'D001855'}, {'text': 'Vitamin B12', 'type': 'Chemical', 'start': 1353, 'end': 1364, 'mesh': 'D014805'}, {'text': 'folinic acid', 'type': 'Chemical', 'start': 1369, 'end': 1381, 'mesh': 'D002955'}, {'text': 'ZDV', 'type': 'Chemical', 'start': 1401, 'end': 1404, 'mesh': 'D015215'}, {'text': 'ZDV', 'type': 'Chemical', 'start': 1460, 'end': 1463, 'mesh': 'D015215'}, {'text': 'myelotoxicity', 'type': 'Disease', 'start': 1472, 'end': 1485, 'mesh': 'D001855'}]"
+114,7858459,Acute confusion induced by a high-dose infusion of 5-fluorouracil and folinic acid.,"A 61-year-old man was treated with combination chemotherapy incorporating cisplatinum, etoposide, high-dose 5-fluorouracil (2,250 mg/m2/24 hours) and folinic acid for an inoperable gastric adenocarcinoma. He developed acute neurologic symptoms of mental confusion, disorientation and irritability, and then lapsed into a deep coma, lasting for approximately 40 hours during the first dose (day 2) of 5-fluorouracil and folinic acid infusion. This complication reappeared on day 25 during the second dose of 5-fluorouracil and folinic acid, which were then the only drugs given. Because folinic acid was unlikely to be associated with this condition, neurotoxicity due to high-dose 5-fluorouracil was highly suspected. The pathogenesis of 5-fluorouracil neurotoxicity may be due to a Krebs cycle blockade by fluoroacetate and fluorocitrate, thiamine deficiency, or dihydrouracil dehydrogenase deficiency. High-dose 5-fluorouracil/folinic acid infusion therapy has recently become a popular regimen for various cancers. It is necessary that both oncologists and neurologists be fully aware of this unusual complication.","[{'text': 'confusion', 'type': 'Disease', 'start': 6, 'end': 15, 'mesh': 'D003221'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 51, 'end': 65, 'mesh': 'D005472'}, {'text': 'folinic acid', 'type': 'Chemical', 'start': 70, 'end': 82, 'mesh': 'D002955'}, {'text': 'cisplatinum', 'type': 'Chemical', 'start': 158, 'end': 169, 'mesh': 'D002945'}, {'text': 'etoposide', 'type': 'Chemical', 'start': 171, 'end': 180, 'mesh': 'D005047'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 192, 'end': 206, 'mesh': 'D005472'}, {'text': 'folinic acid', 'type': 'Chemical', 'start': 234, 'end': 246, 'mesh': 'D002955'}, {'text': 'gastric adenocarcinoma', 'type': 'Disease', 'start': 265, 'end': 287, 'mesh': 'D013274'}, {'text': 'confusion', 'type': 'Disease', 'start': 338, 'end': 347, 'mesh': 'D003221'}, {'text': 'disorientation', 'type': 'Disease', 'start': 349, 'end': 363, 'mesh': 'D003221'}, {'text': 'irritability', 'type': 'Disease', 'start': 368, 'end': 380, 'mesh': 'D001523'}, {'text': 'coma', 'type': 'Disease', 'start': 410, 'end': 414, 'mesh': 'D003128'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 484, 'end': 498, 'mesh': 'D005472'}, {'text': 'folinic acid', 'type': 'Chemical', 'start': 503, 'end': 515, 'mesh': 'D002955'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 591, 'end': 605, 'mesh': 'D005472'}, {'text': 'folinic acid', 'type': 'Chemical', 'start': 610, 'end': 622, 'mesh': 'D002955'}, {'text': 'folinic acid', 'type': 'Chemical', 'start': 670, 'end': 682, 'mesh': 'D002955'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 734, 'end': 747, 'mesh': 'D020258'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 765, 'end': 779, 'mesh': 'D005472'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 822, 'end': 836, 'mesh': 'D005472'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 837, 'end': 850, 'mesh': 'D020258'}, {'text': 'fluoroacetate', 'type': 'Chemical', 'start': 891, 'end': 904, 'mesh': 'D005463'}, {'text': 'fluorocitrate', 'type': 'Chemical', 'start': 909, 'end': 922, 'mesh': 'C007744'}, {'text': 'thiamine', 'type': 'Chemical', 'start': 924, 'end': 932, 'mesh': 'D013831'}, {'text': 'dihydrouracil', 'type': 'Chemical', 'start': 948, 'end': 961, 'mesh': 'C007419'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 998, 'end': 1012, 'mesh': 'D005472'}, {'text': 'folinic acid', 'type': 'Chemical', 'start': 1013, 'end': 1025, 'mesh': 'D002955'}, {'text': 'cancers', 'type': 'Disease', 'start': 1093, 'end': 1100, 'mesh': 'D009369'}]"
+115,7862923,Effect of switching carbamazepine to oxcarbazepine on the plasma levels of neuroleptics. A case report.,"Carbamazepine was switched to its 10-keto analogue oxcarbazepine among six difficult-to-treat schizophrenic or organic psychotic patients using concomitantly haloperidol, chlorpromazine or clozapine. This change resulted within 2-4 weeks in the 50-200% increase in the plasma levels of these neuroleptics and the appearance of extrapyramidal symptoms. None of the patients showed any clinical deteriotation during the following 3-6 months. The results of this case report support the idea that in contrast with carbamazepine oxcarbazepine does not induce the hepatic microsomal enzyme systems regulating the inactivation of antipsychotic drugs.","[{'text': 'carbamazepine', 'type': 'Chemical', 'start': 20, 'end': 33, 'mesh': 'D002220'}, {'text': 'oxcarbazepine', 'type': 'Chemical', 'start': 37, 'end': 50, 'mesh': 'C036006'}, {'text': 'Carbamazepine', 'type': 'Chemical', 'start': 104, 'end': 117, 'mesh': 'D002220'}, {'text': 'oxcarbazepine', 'type': 'Chemical', 'start': 155, 'end': 168, 'mesh': 'C036006'}, {'text': 'schizophrenic', 'type': 'Disease', 'start': 198, 'end': 211, 'mesh': 'D012559'}, {'text': 'organic psychotic', 'type': 'Disease', 'start': 215, 'end': 232, 'mesh': 'D019965'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 262, 'end': 273, 'mesh': 'D006220'}, {'text': 'chlorpromazine', 'type': 'Chemical', 'start': 275, 'end': 289, 'mesh': 'D002746'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 293, 'end': 302, 'mesh': 'D003024'}, {'text': 'extrapyramidal symptoms', 'type': 'Disease', 'start': 431, 'end': 454, 'mesh': 'D001480'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 615, 'end': 628, 'mesh': 'D002220'}, {'text': 'oxcarbazepine', 'type': 'Chemical', 'start': 629, 'end': 642, 'mesh': 'C036006'}]"
+116,7919560,Erythema multiforme and hypersensitivity myocarditis caused by ampicillin.,"OBJECTIVE: To report a case of erythema multiforme and hypersensitivity myocarditis caused by ampicillin. CASE SUMMARY: A 13-year-old boy was treated with ampicillin and gentamicin because of suspected septicemia. Medications were discontinued when erythema multiforme and congestive heart failure caused by myocarditis occurred. The patient was treated with methylprednisolone and gradually improved. Macrophage-migration inhibition (MIF) test with ampicillin was positive. DISCUSSION: After most infections causing erythema multiforme and myocarditis were ruled out, a drug-induced allergic reaction was suspected. Positive MIF test for ampicillin showed sensitization of the patient's lymphocytes to ampicillin. CONCLUSIONS: Hypersensitivity myocarditis is a rare and dangerous manifestation of allergy to penicillins.","[{'text': 'Erythema multiforme', 'type': 'Disease', 'start': 0, 'end': 19, 'mesh': 'D004892'}, {'text': 'hypersensitivity myocarditis', 'type': 'Disease', 'start': 24, 'end': 52, 'mesh': 'D009205'}, {'text': 'ampicillin', 'type': 'Chemical', 'start': 63, 'end': 73, 'mesh': 'D000667'}, {'text': 'erythema multiforme', 'type': 'Disease', 'start': 106, 'end': 125, 'mesh': 'D004892'}, {'text': 'hypersensitivity myocarditis', 'type': 'Disease', 'start': 130, 'end': 158, 'mesh': 'D009205'}, {'text': 'ampicillin', 'type': 'Chemical', 'start': 169, 'end': 179, 'mesh': 'D000667'}, {'text': 'ampicillin', 'type': 'Chemical', 'start': 230, 'end': 240, 'mesh': 'D000667'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 245, 'end': 255, 'mesh': 'D005839'}, {'text': 'septicemia', 'type': 'Disease', 'start': 277, 'end': 287, 'mesh': 'D018805'}, {'text': 'erythema multiforme', 'type': 'Disease', 'start': 324, 'end': 343, 'mesh': 'D004892'}, {'text': 'congestive heart failure', 'type': 'Disease', 'start': 348, 'end': 372, 'mesh': 'D006333'}, {'text': 'myocarditis', 'type': 'Disease', 'start': 383, 'end': 394, 'mesh': 'D009205'}, {'text': 'methylprednisolone', 'type': 'Chemical', 'start': 434, 'end': 452, 'mesh': 'D008775'}, {'text': 'ampicillin', 'type': 'Chemical', 'start': 525, 'end': 535, 'mesh': 'D000667'}, {'text': 'infections', 'type': 'Disease', 'start': 573, 'end': 583, 'mesh': 'D007239'}, {'text': 'erythema multiforme', 'type': 'Disease', 'start': 592, 'end': 611, 'mesh': 'D004892'}, {'text': 'myocarditis', 'type': 'Disease', 'start': 616, 'end': 627, 'mesh': 'D009205'}, {'text': 'drug-induced allergic reaction', 'type': 'Disease', 'start': 646, 'end': 676, 'mesh': 'D004342'}, {'text': 'ampicillin', 'type': 'Chemical', 'start': 714, 'end': 724, 'mesh': 'D000667'}, {'text': 'ampicillin', 'type': 'Chemical', 'start': 778, 'end': 788, 'mesh': 'D000667'}, {'text': 'Hypersensitivity myocarditis', 'type': 'Disease', 'start': 803, 'end': 831, 'mesh': 'D009205'}, {'text': 'allergy', 'type': 'Disease', 'start': 873, 'end': 880, 'mesh': 'D004342'}, {'text': 'penicillins', 'type': 'Chemical', 'start': 884, 'end': 895, 'mesh': 'D010406'}]"
+117,8092427,Immediate allergic reactions to amoxicillin.,"A large group of patients with suspected allergic reactions to beta-lactam antibiotics was evaluated. A detailed clinical history, together with skin tests, RAST (radioallergosorbent test), and controlled challenge tests, was used to establish whether patients allergic to beta-lactam antibiotics had selective immediate allergic responses to amoxicillin (AX) or were cross-reacting with other penicillin derivatives. Skin tests were performed with benzylpenicilloyl-poly-L-lysine (BPO-PLL), benzylpenicilloate, benzylpenicillin (PG), ampicillin (AMP), and AX. RAST for BPO-PLL and AX-PLL was done. When both skin test and RAST for BPO were negative, single-blind, placebo-controlled challenge tests were done to ensure tolerance of PG or sensitivity to AX. A total of 177 patients were diagnosed as allergic to beta-lactam antibiotics. We selected the 54 (30.5%) cases of immediate AX allergy with good tolerance of PG. Anaphylaxis was seen in 37 patients (69%), the other 17 (31%) having urticaria and/or angioedema. All the patients were skin test negative to BPO; 49 of 51 (96%) were also negative to MDM, and 44 of 46 (96%) to PG. Skin tests with AX were positive in 34 (63%) patients. RAST was positive for AX in 22 patients (41%) and to BPO in just 5 (9%). None of the sera with negative RAST for AX were positive to BPO. Challenge tests with AX were performed in 23 subjects (43%) to establish the diagnosis of immediate allergic reaction to AX, and in 15 cases (28%) both skin test and RAST for AX were negative. PG was well tolerated by all 54 patients. We describe the largest group of AX-allergic patients who have tolerated PG reported so far. Diagnosis of these patients can be achieved only if specific AX-related reagents are employed. Further studies are necessary to determine the exact extent of this problem and to improve the efficacy of diagnostic methods.","[{'text': 'allergic reactions', 'type': 'Disease', 'start': 10, 'end': 28, 'mesh': 'D004342'}, {'text': 'amoxicillin', 'type': 'Chemical', 'start': 32, 'end': 43, 'mesh': 'D000658'}, {'text': 'allergic reactions', 'type': 'Disease', 'start': 86, 'end': 104, 'mesh': 'D004342'}, {'text': 'beta-lactam', 'type': 'Chemical', 'start': 108, 'end': 119, 'mesh': 'D047090'}, {'text': 'allergic', 'type': 'Disease', 'start': 306, 'end': 314, 'mesh': 'D004342'}, {'text': 'beta-lactam', 'type': 'Chemical', 'start': 318, 'end': 329, 'mesh': 'D047090'}, {'text': 'allergic', 'type': 'Disease', 'start': 366, 'end': 374, 'mesh': 'D004342'}, {'text': 'amoxicillin', 'type': 'Chemical', 'start': 388, 'end': 399, 'mesh': 'D000658'}, {'text': 'AX', 'type': 'Chemical', 'start': 401, 'end': 403, 'mesh': 'D000658'}, {'text': 'penicillin', 'type': 'Chemical', 'start': 439, 'end': 449, 'mesh': 'D010406'}, {'text': 'benzylpenicilloyl-poly-L-lysine', 'type': 'Chemical', 'start': 494, 'end': 525, 'mesh': '-1'}, {'text': 'BPO-PLL', 'type': 'Chemical', 'start': 527, 'end': 534, 'mesh': '-1'}, {'text': 'benzylpenicilloate', 'type': 'Chemical', 'start': 537, 'end': 555, 'mesh': '-1'}, {'text': 'benzylpenicillin', 'type': 'Chemical', 'start': 557, 'end': 573, 'mesh': 'D010400'}, {'text': 'PG', 'type': 'Chemical', 'start': 575, 'end': 577, 'mesh': 'D010400'}, {'text': 'ampicillin', 'type': 'Chemical', 'start': 580, 'end': 590, 'mesh': 'D000667'}, {'text': 'AMP', 'type': 'Chemical', 'start': 592, 'end': 595, 'mesh': 'D000667'}, {'text': 'AX', 'type': 'Chemical', 'start': 602, 'end': 604, 'mesh': 'D000658'}, {'text': 'BPO-PLL', 'type': 'Chemical', 'start': 615, 'end': 622, 'mesh': '-1'}, {'text': 'AX', 'type': 'Chemical', 'start': 627, 'end': 629, 'mesh': 'D000658'}, {'text': 'BPO', 'type': 'Chemical', 'start': 677, 'end': 680, 'mesh': '-1'}, {'text': 'PG', 'type': 'Chemical', 'start': 778, 'end': 780, 'mesh': 'D010400'}, {'text': 'AX', 'type': 'Chemical', 'start': 799, 'end': 801, 'mesh': 'D000658'}, {'text': 'allergic', 'type': 'Disease', 'start': 845, 'end': 853, 'mesh': 'D004342'}, {'text': 'beta-lactam', 'type': 'Chemical', 'start': 857, 'end': 868, 'mesh': 'D047090'}, {'text': 'AX', 'type': 'Chemical', 'start': 928, 'end': 930, 'mesh': 'D000658'}, {'text': 'allergy', 'type': 'Disease', 'start': 931, 'end': 938, 'mesh': 'D004342'}, {'text': 'PG', 'type': 'Chemical', 'start': 962, 'end': 964, 'mesh': 'D010400'}, {'text': 'Anaphylaxis', 'type': 'Disease', 'start': 966, 'end': 977, 'mesh': 'D000707'}, {'text': 'urticaria', 'type': 'Disease', 'start': 1035, 'end': 1044, 'mesh': 'D014581'}, {'text': 'angioedema', 'type': 'Disease', 'start': 1052, 'end': 1062, 'mesh': 'D000799'}, {'text': 'BPO', 'type': 'Chemical', 'start': 1108, 'end': 1111, 'mesh': '-1'}, {'text': 'MDM', 'type': 'Disease', 'start': 1150, 'end': 1153, 'mesh': 'D007645'}, {'text': 'PG', 'type': 'Chemical', 'start': 1177, 'end': 1179, 'mesh': 'D010400'}, {'text': 'AX', 'type': 'Chemical', 'start': 1197, 'end': 1199, 'mesh': 'D000658'}, {'text': 'AX', 'type': 'Chemical', 'start': 1258, 'end': 1260, 'mesh': 'D000658'}, {'text': 'BPO', 'type': 'Chemical', 'start': 1289, 'end': 1292, 'mesh': '-1'}, {'text': 'AX', 'type': 'Chemical', 'start': 1349, 'end': 1351, 'mesh': 'D000658'}, {'text': 'BPO', 'type': 'Chemical', 'start': 1369, 'end': 1372, 'mesh': '-1'}, {'text': 'AX', 'type': 'Chemical', 'start': 1395, 'end': 1397, 'mesh': 'D000658'}, {'text': 'allergic reaction', 'type': 'Disease', 'start': 1474, 'end': 1491, 'mesh': 'D004342'}, {'text': 'AX', 'type': 'Chemical', 'start': 1495, 'end': 1497, 'mesh': 'D000658'}, {'text': 'AX', 'type': 'Chemical', 'start': 1549, 'end': 1551, 'mesh': 'D000658'}, {'text': 'PG', 'type': 'Chemical', 'start': 1567, 'end': 1569, 'mesh': 'D010400'}, {'text': 'AX', 'type': 'Chemical', 'start': 1642, 'end': 1644, 'mesh': 'D000658'}, {'text': 'allergic', 'type': 'Disease', 'start': 1645, 'end': 1653, 'mesh': 'D004342'}, {'text': 'PG', 'type': 'Chemical', 'start': 1682, 'end': 1684, 'mesh': 'D010400'}, {'text': 'AX', 'type': 'Chemical', 'start': 1763, 'end': 1765, 'mesh': 'D000658'}]"
+118,8638206,Persistent paralysis after prolonged use of atracurium in the absence of corticosteroids.,"Neuromuscular blocking agents (NMBAs) are often used for patients requiring prolonged mechanical ventilation. Reports of persistent paralysis after the discontinuance of these drugs have most often involved aminosteroid-based NMBAs such as vecuronium bromide, especially when used in conjunction with corticosteroids. Atracurium besylate, a short-acting benzylisoquinolinium NMBA that is eliminated independently of renal or hepatic function, has also been associated with persistent paralysis, but only when used with corticosteroids. We report a case of atracurium-related paralysis persisting for approximately 50 hours in a patient who was not treated with corticosteroids.","[{'text': 'paralysis', 'type': 'Disease', 'start': 11, 'end': 20, 'mesh': 'D010243'}, {'text': 'atracurium', 'type': 'Chemical', 'start': 44, 'end': 54, 'mesh': 'D001279'}, {'text': 'paralysis', 'type': 'Disease', 'start': 222, 'end': 231, 'mesh': 'D010243'}, {'text': 'vecuronium bromide', 'type': 'Chemical', 'start': 330, 'end': 348, 'mesh': 'D014673'}, {'text': 'Atracurium besylate', 'type': 'Chemical', 'start': 408, 'end': 427, 'mesh': 'D001279'}, {'text': 'benzylisoquinolinium', 'type': 'Chemical', 'start': 444, 'end': 464, 'mesh': '-1'}, {'text': 'paralysis', 'type': 'Disease', 'start': 574, 'end': 583, 'mesh': 'D010243'}, {'text': 'atracurium', 'type': 'Chemical', 'start': 646, 'end': 656, 'mesh': 'D001279'}, {'text': 'paralysis', 'type': 'Disease', 'start': 665, 'end': 674, 'mesh': 'D010243'}]"
+119,8669433,Habitual use of acetaminophen as a risk factor for chronic renal failure: a comparison with phenacetin.,"Six epidemiologic studies in the United States and Europe indicate that habitual use of phenacetin is associated with the development of chronic renal failure and end-stage renal disease (ESRD), with a relative risk in the range of 4 to 19. As a result of these and other studies, phenacetin has now been withdrawn from the market in most countries. However, three case control studies, one each in North Carolina, northern Maryland, and West Berlin, Germany, showed that habitual use of acetaminophen is also associated with chronic renal failure and ESRD, with a relative risk in the range of 2 to 4. These studies suggest that both phenacetin and acetaminophen may contribute to the burden of ESRD, with the risk of the latter being somewhat less than that of the former. This apparent difference in risk may not be due to differences in nephrotoxic potential of the drugs themselves. A lower relative risk would be expected for acetaminophen if the risk of both drugs in combination with other analgesics was higher than the risk of either agent alone. Thus, acetaminophen has been used both as a single agent and in combination with other analgesics, whereas phenacetin was available only in combinations. The possibility that habitual use of acetaminophen alone increases the risk of ESRD has not been clearly demonstrated, but cannot be dismissed.","[{'text': 'acetaminophen', 'type': 'Chemical', 'start': 16, 'end': 29, 'mesh': 'D000082'}, {'text': 'chronic renal failure', 'type': 'Disease', 'start': 51, 'end': 72, 'mesh': 'D007676'}, {'text': 'phenacetin', 'type': 'Chemical', 'start': 92, 'end': 102, 'mesh': 'D010615'}, {'text': 'phenacetin', 'type': 'Chemical', 'start': 192, 'end': 202, 'mesh': 'D010615'}, {'text': 'chronic renal failure', 'type': 'Disease', 'start': 241, 'end': 262, 'mesh': 'D007676'}, {'text': 'end-stage renal disease', 'type': 'Disease', 'start': 267, 'end': 290, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 292, 'end': 296, 'mesh': 'D007676'}, {'text': 'phenacetin', 'type': 'Chemical', 'start': 385, 'end': 395, 'mesh': 'D010615'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 592, 'end': 605, 'mesh': 'D000082'}, {'text': 'chronic renal failure', 'type': 'Disease', 'start': 630, 'end': 651, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 656, 'end': 660, 'mesh': 'D007676'}, {'text': 'phenacetin', 'type': 'Chemical', 'start': 739, 'end': 749, 'mesh': 'D010615'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 754, 'end': 767, 'mesh': 'D000082'}, {'text': 'ESRD', 'type': 'Disease', 'start': 800, 'end': 804, 'mesh': 'D007676'}, {'text': 'nephrotoxic', 'type': 'Disease', 'start': 945, 'end': 956, 'mesh': 'D007674'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 1036, 'end': 1049, 'mesh': 'D000082'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 1167, 'end': 1180, 'mesh': 'D000082'}, {'text': 'phenacetin', 'type': 'Chemical', 'start': 1268, 'end': 1278, 'mesh': 'D010615'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 1352, 'end': 1365, 'mesh': 'D000082'}, {'text': 'ESRD', 'type': 'Disease', 'start': 1394, 'end': 1398, 'mesh': 'D007676'}]"
+120,8690168,Reduction of heparan sulphate-associated anionic sites in the glomerular basement membrane of rats with streptozotocin-induced diabetic nephropathy.,"Heparan sulphate-associated anionic sites in the glomerular basement membrane were studied in rats 8 months after induction of diabetes by streptozotocin and in age- adn sex-matched control rats, employing the cationic dye cuprolinic blue. Morphometric analysis at the ultrastructural level was performed using a computerized image processor. The heparan sulphate specificity of the cuprolinic blue staining was demonstrated by glycosaminoglycan-degrading enzymes, showing that pretreatment of the sections with heparitinase abolished all staining, whereas chondroitinase ABC had no effect. The majority of anionic sites (74% in diabetic and 81% in control rats) were found within the lamina rara externa of the glomerular basement membrane. A minority of anionic sites were scattered throughout the lamina densa and lamina rara interna, and were significantly smaller than those in the lamina rara externa of the glomerular basement membrane (p<0.001 and p<0.01 for diabetic and control rats, respectively). Diabetic rats progressively developed albuminuria reaching 40.3 (32.2-62.0) mg/24 h after 8 months in contrast to the control animals (0.8 (0.2-0.9) mg/24 h, p<0.002). At the same time, the number of heparan sulphate anionic sites and the total anionic site surface (number of anionic sites x mean anionic site surface) in the lamina rara externa of the glomerular basement membrane was reduced by 19% (p<0.021) and by 26% (p<0.02), respectively. Number and total anionic site surface in the remaining part of the glomerular basement membrane (lamina densa and lamina rara interna) were not significantly changed. We conclude that in streptozotocin-diabetic rats with an increased urinary albumin excretion, a reduced heparan sulphate charge barrier/density is found at the lamina rara externa of the glomerular basement membrane.","[{'text': 'heparan sulphate', 'type': 'Chemical', 'start': 13, 'end': 29, 'mesh': 'D006497'}, {'text': 'streptozotocin', 'type': 'Chemical', 'start': 104, 'end': 118, 'mesh': 'D013311'}, {'text': 'diabetic nephropathy', 'type': 'Disease', 'start': 127, 'end': 147, 'mesh': 'D003928'}, {'text': 'Heparan sulphate', 'type': 'Chemical', 'start': 149, 'end': 165, 'mesh': 'D006497'}, {'text': 'diabetes', 'type': 'Disease', 'start': 276, 'end': 284, 'mesh': 'D003920'}, {'text': 'streptozotocin', 'type': 'Chemical', 'start': 288, 'end': 302, 'mesh': 'D013311'}, {'text': 'cuprolinic blue', 'type': 'Chemical', 'start': 372, 'end': 387, 'mesh': 'C015445'}, {'text': 'heparan sulphate', 'type': 'Chemical', 'start': 496, 'end': 512, 'mesh': 'D006497'}, {'text': 'cuprolinic blue', 'type': 'Chemical', 'start': 532, 'end': 547, 'mesh': 'C015445'}, {'text': 'glycosaminoglycan', 'type': 'Chemical', 'start': 577, 'end': 594, 'mesh': 'D006025'}, {'text': 'diabetic', 'type': 'Disease', 'start': 778, 'end': 786, 'mesh': 'D003920'}, {'text': 'diabetic', 'type': 'Disease', 'start': 1116, 'end': 1124, 'mesh': 'D003920'}, {'text': 'Diabetic', 'type': 'Disease', 'start': 1158, 'end': 1166, 'mesh': 'D003920'}, {'text': 'albuminuria', 'type': 'Disease', 'start': 1196, 'end': 1207, 'mesh': 'D000419'}, {'text': 'heparan sulphate', 'type': 'Chemical', 'start': 1358, 'end': 1374, 'mesh': 'D006497'}, {'text': 'streptozotocin', 'type': 'Chemical', 'start': 1792, 'end': 1806, 'mesh': 'D013311'}, {'text': 'diabetic', 'type': 'Disease', 'start': 1807, 'end': 1815, 'mesh': 'D003920'}, {'text': 'heparan sulphate', 'type': 'Chemical', 'start': 1876, 'end': 1892, 'mesh': 'D006497'}]"
+121,8739323,Effect of some anticancer drugs and combined chemotherapy on renal toxicity.,"The nephrotoxic action of anticancer drugs such as nitrogranulogen (NG), methotrexate (MTX), 5-fluorouracil (5-FU) and cyclophosphamide (CY) administered alone or in combination [MTX + 5-FU + CY (CMF)] was evaluated in experiments on Wistar rats. After drug administration, creatinine concentrations in the plasma and in the urine of the rats were determined, as well as creatinine clearance. Histopathologic evaluation of the kidneys was also performed. After MTX administration a significant increase (p = 0.0228) in the plasma creatinine concentration and a significant (p = 0.0001) decrease in creatinine clearance was noted compared to controls. After the administration of NG, 5-FU and CY neither a statistically significant increase in creatinine concentration nor an increase in creatinine clearance was observed compared to the group receiving no cytostatics. Following polytherapy according to the CMF regimen, a statistically significant decrease (p = 0.0343) in creatinine clearance was found, but creatinine concentration did not increase significantly compared to controls. CY caused hemorrhagic cystitis in 40% of rats, but it did not cause this complication when combined with 5-FU and MTX. Histologic changes were found in rat kidneys after administration of MTX, CY and NG, while no such change was observed after 5-FU and joint administration of MTX + 5-FU + CY compared to controls. Our studies indicate that nephrotoxicity of MTX + 5-FU + CY administered jointly is lower than in monotherapy.","[{'text': 'renal toxicity', 'type': 'Disease', 'start': 61, 'end': 75, 'mesh': 'D007674'}, {'text': 'nephrotoxic', 'type': 'Disease', 'start': 81, 'end': 92, 'mesh': 'D007674'}, {'text': 'nitrogranulogen', 'type': 'Chemical', 'start': 128, 'end': 143, 'mesh': 'D008466'}, {'text': 'NG', 'type': 'Chemical', 'start': 145, 'end': 147, 'mesh': 'D008466'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 150, 'end': 162, 'mesh': 'D008727'}, {'text': 'MTX', 'type': 'Chemical', 'start': 164, 'end': 167, 'mesh': 'D008727'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 170, 'end': 184, 'mesh': 'D005472'}, {'text': '5-FU', 'type': 'Chemical', 'start': 186, 'end': 190, 'mesh': 'D005472'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 196, 'end': 212, 'mesh': 'D003520'}, {'text': 'CY', 'type': 'Chemical', 'start': 214, 'end': 216, 'mesh': 'D003520'}, {'text': 'MTX', 'type': 'Chemical', 'start': 256, 'end': 259, 'mesh': 'D008727'}, {'text': '5-FU', 'type': 'Chemical', 'start': 262, 'end': 266, 'mesh': 'D005472'}, {'text': 'CY', 'type': 'Chemical', 'start': 269, 'end': 271, 'mesh': 'D003520'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 351, 'end': 361, 'mesh': 'D003404'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 448, 'end': 458, 'mesh': 'D003404'}, {'text': 'MTX', 'type': 'Chemical', 'start': 538, 'end': 541, 'mesh': 'D008727'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 607, 'end': 617, 'mesh': 'D003404'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 675, 'end': 685, 'mesh': 'D003404'}, {'text': 'NG', 'type': 'Chemical', 'start': 756, 'end': 758, 'mesh': 'D008466'}, {'text': '5-FU', 'type': 'Chemical', 'start': 760, 'end': 764, 'mesh': 'D005472'}, {'text': 'CY', 'type': 'Chemical', 'start': 769, 'end': 771, 'mesh': 'D003520'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 820, 'end': 830, 'mesh': 'D003404'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 864, 'end': 874, 'mesh': 'D003404'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1051, 'end': 1061, 'mesh': 'D003404'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1087, 'end': 1097, 'mesh': 'D003404'}, {'text': 'CY', 'type': 'Chemical', 'start': 1165, 'end': 1167, 'mesh': 'D003520'}, {'text': '5-FU', 'type': 'Chemical', 'start': 1270, 'end': 1274, 'mesh': 'D005472'}, {'text': 'MTX', 'type': 'Chemical', 'start': 1279, 'end': 1282, 'mesh': 'D008727'}, {'text': 'MTX', 'type': 'Chemical', 'start': 1353, 'end': 1356, 'mesh': 'D008727'}, {'text': 'CY', 'type': 'Chemical', 'start': 1358, 'end': 1360, 'mesh': 'D003520'}, {'text': 'NG', 'type': 'Chemical', 'start': 1365, 'end': 1367, 'mesh': 'D008466'}, {'text': '5-FU', 'type': 'Chemical', 'start': 1409, 'end': 1413, 'mesh': 'D005472'}, {'text': 'MTX', 'type': 'Chemical', 'start': 1442, 'end': 1445, 'mesh': 'D008727'}, {'text': '5-FU', 'type': 'Chemical', 'start': 1448, 'end': 1452, 'mesh': 'D005472'}, {'text': 'CY', 'type': 'Chemical', 'start': 1455, 'end': 1457, 'mesh': 'D003520'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1506, 'end': 1520, 'mesh': 'D007674'}, {'text': 'MTX', 'type': 'Chemical', 'start': 1524, 'end': 1527, 'mesh': 'D008727'}, {'text': '5-FU', 'type': 'Chemical', 'start': 1530, 'end': 1534, 'mesh': 'D005472'}, {'text': 'CY', 'type': 'Chemical', 'start': 1537, 'end': 1539, 'mesh': 'D003520'}]"
+122,8752018,Lithium-associated cognitive and functional deficits reduced by a switch to divalproex sodium: a case series.,"BACKGROUND: Lithium remains a first-line treatment for the acute and maintenance treatment of bipolar disorder. Although much has been written about the management of the more common adverse effects of lithium, such as polyuria and tremor, more subtle lithium side effects such as cognitive deficits, loss of creativity, and functional impairments remain understudied. This report summarizes our experience in switching bipolar patients from lithium to divalproex sodium to alleviate such cognitive and functional impairments. METHOD: Open, case series design. RESULTS: We report seven cases where substitution of lithium, either fully or partially, with divalproex sodium was extremely helpful in reducing the cognitive, motivational, or creative deficits attributed to lithium in our bipolar patients. CONCLUSION: In this preliminary report, divalproex sodium was a superior alternative to lithium in bipolar patients experiencing cognitive deficits, loss of creativity, and functional impairments.","[{'text': 'Lithium', 'type': 'Chemical', 'start': 0, 'end': 7, 'mesh': 'D008094'}, {'text': 'cognitive and functional deficits', 'type': 'Disease', 'start': 19, 'end': 52, 'mesh': 'D003072'}, {'text': 'divalproex sodium', 'type': 'Chemical', 'start': 76, 'end': 93, 'mesh': 'D014635'}, {'text': 'Lithium', 'type': 'Chemical', 'start': 122, 'end': 129, 'mesh': 'D008094'}, {'text': 'bipolar disorder', 'type': 'Disease', 'start': 204, 'end': 220, 'mesh': 'D001714'}, {'text': 'lithium', 'type': 'Chemical', 'start': 312, 'end': 319, 'mesh': 'D008094'}, {'text': 'polyuria', 'type': 'Disease', 'start': 329, 'end': 337, 'mesh': 'D011141'}, {'text': 'tremor', 'type': 'Disease', 'start': 342, 'end': 348, 'mesh': 'D014202'}, {'text': 'lithium', 'type': 'Chemical', 'start': 362, 'end': 369, 'mesh': 'D008094'}, {'text': 'cognitive deficits', 'type': 'Disease', 'start': 391, 'end': 409, 'mesh': 'D003072'}, {'text': 'loss of creativity', 'type': 'Disease', 'start': 411, 'end': 429, 'mesh': 'D003072'}, {'text': 'functional impairments', 'type': 'Disease', 'start': 435, 'end': 457, 'mesh': 'D003072'}, {'text': 'bipolar', 'type': 'Disease', 'start': 530, 'end': 537, 'mesh': 'D001714'}, {'text': 'lithium', 'type': 'Chemical', 'start': 552, 'end': 559, 'mesh': 'D008094'}, {'text': 'divalproex sodium', 'type': 'Chemical', 'start': 563, 'end': 580, 'mesh': 'D014635'}, {'text': 'cognitive and functional impairments', 'type': 'Disease', 'start': 599, 'end': 635, 'mesh': 'D003072'}, {'text': 'lithium', 'type': 'Chemical', 'start': 724, 'end': 731, 'mesh': 'D008094'}, {'text': 'divalproex sodium', 'type': 'Chemical', 'start': 765, 'end': 782, 'mesh': 'D014635'}, {'text': 'cognitive, motivational, or creative deficits', 'type': 'Disease', 'start': 821, 'end': 866, 'mesh': 'D003072'}, {'text': 'lithium', 'type': 'Chemical', 'start': 881, 'end': 888, 'mesh': 'D008094'}, {'text': 'bipolar', 'type': 'Disease', 'start': 896, 'end': 903, 'mesh': 'D001714'}, {'text': 'divalproex sodium', 'type': 'Chemical', 'start': 954, 'end': 971, 'mesh': 'D014635'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1002, 'end': 1009, 'mesh': 'D008094'}, {'text': 'bipolar', 'type': 'Disease', 'start': 1013, 'end': 1020, 'mesh': 'D001714'}, {'text': 'cognitive deficits', 'type': 'Disease', 'start': 1043, 'end': 1061, 'mesh': 'D003072'}, {'text': 'loss of creativity', 'type': 'Disease', 'start': 1063, 'end': 1081, 'mesh': 'D003072'}, {'text': 'functional impairments', 'type': 'Disease', 'start': 1087, 'end': 1109, 'mesh': 'D003072'}]"
+123,9390208,Treatment of previously treated metastatic breast cancer by mitoxantrone and 48-hour continuous infusion of high-dose 5-FU and leucovorin (MFL): low palliative benefit and high treatment-related toxicity.,"For previously treated advanced breast cancer, there is no standard second-line therapy. Combination chemotherapy with mitoxantrone, high-dose 5-fluorouracil (5-FU) and leucovorin (MFL regimen) had been reported as an effective and well tolerated regimen. From October 1993 to November 1995, we treated 13 patients with previously chemotherapy-treated metastatic breast cancer by mitoxantrone, 12 mg/m2, on day 1 and continuous infusion of 5-FU, 3000 mg/m2, together with leucovorin, 300 mg/m2, for 48 h from day 1 to 2. Each course of chemotherapy was given every 4 weeks. Most of these patients had more than two metastatic sites, with lung metastasis predominant. Seven patients had been treated with anthracycline. Seven patients had previously received radiotherapy and seven had received hormone therapy. Median number of courses of MFL regimen given was six and the median cumulative dose of mitoxantrone was 68.35 mg/m2. One patient had complete response, seven had stable disease, none had partial response and five had progressive disease. The overall objective response rate was 7.6%. The median follow-up period was 14 months. Median survival was 16 months. Median progression-free survival was 5 months. A complete responder had relapse-free survival up to 17 months. Major toxicities were cardiotoxicity and leukopenia. Eight patients were dead in the last follow-up; two of them died of treatment-related toxicity. The MFL regimen achieves little palliative benefit and induces severe toxicity at a fairly high rate. Administration of this regimen to breast cancer patients who have been treated by chemotherapy and those with impaired heart function requires careful attention.","[{'text': 'breast cancer', 'type': 'Disease', 'start': 43, 'end': 56, 'mesh': 'D001943'}, {'text': 'mitoxantrone', 'type': 'Chemical', 'start': 60, 'end': 72, 'mesh': 'D008942'}, {'text': '5-FU', 'type': 'Chemical', 'start': 118, 'end': 122, 'mesh': 'D005472'}, {'text': 'leucovorin', 'type': 'Chemical', 'start': 127, 'end': 137, 'mesh': 'D002955'}, {'text': 'MFL', 'type': 'Chemical', 'start': 139, 'end': 142, 'mesh': 'C085788'}, {'text': 'toxicity', 'type': 'Disease', 'start': 195, 'end': 203, 'mesh': 'D064420'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 237, 'end': 250, 'mesh': 'D001943'}, {'text': 'mitoxantrone', 'type': 'Chemical', 'start': 324, 'end': 336, 'mesh': 'D008942'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 348, 'end': 362, 'mesh': 'D005472'}, {'text': '5-FU', 'type': 'Chemical', 'start': 364, 'end': 368, 'mesh': 'D005472'}, {'text': 'leucovorin', 'type': 'Chemical', 'start': 374, 'end': 384, 'mesh': 'D002955'}, {'text': 'MFL regimen', 'type': 'Chemical', 'start': 386, 'end': 397, 'mesh': 'C085788'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 568, 'end': 581, 'mesh': 'D001943'}, {'text': 'mitoxantrone', 'type': 'Chemical', 'start': 585, 'end': 597, 'mesh': 'D008942'}, {'text': '5-FU', 'type': 'Chemical', 'start': 645, 'end': 649, 'mesh': 'D005472'}, {'text': 'leucovorin', 'type': 'Chemical', 'start': 677, 'end': 687, 'mesh': 'D002955'}, {'text': 'anthracycline', 'type': 'Chemical', 'start': 909, 'end': 922, 'mesh': 'D018943'}, {'text': 'MFL regimen', 'type': 'Chemical', 'start': 1044, 'end': 1055, 'mesh': 'C085788'}, {'text': 'mitoxantrone', 'type': 'Chemical', 'start': 1104, 'end': 1116, 'mesh': 'D008942'}, {'text': 'toxicities', 'type': 'Disease', 'start': 1492, 'end': 1502, 'mesh': 'D064420'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1508, 'end': 1522, 'mesh': 'D066126'}, {'text': 'leukopenia', 'type': 'Disease', 'start': 1527, 'end': 1537, 'mesh': 'D007970'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1625, 'end': 1633, 'mesh': 'D064420'}, {'text': 'MFL regimen', 'type': 'Chemical', 'start': 1639, 'end': 1650, 'mesh': 'C085788'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1705, 'end': 1713, 'mesh': 'D064420'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 1771, 'end': 1784, 'mesh': 'D001943'}, {'text': 'impaired heart function', 'type': 'Disease', 'start': 1847, 'end': 1870, 'mesh': 'D006331'}]"
+124,9406968,Upregulation of the expression of vasopressin gene in the paraventricular and supraoptic nuclei of the lithium-induced diabetes insipidus rat.,"The expression of arginine vasopressin (AVP) gene in the paraventricular (PVN) and supraoptic nuclei (SON) was investigated in rats with lithium (Li)-induced polyuria, using in situ hybridization histochemistry and radioimmunoassay. The male Wistar rats consuming a diet that contained LiCl (60 mmol/kg) for 4 weeks developed marked polyuria. The Li-treated rats produced a large volume of hypotonic urine with low ionic concentrations. Plasma sodium concentrations were found to be slightly increased in the Li-treated rats compared with those in controls. Plasma concentration of AVP and transcripts of AVP gene in the PVN and SON were significantly increased in the Li-treated rats compared with controls. These results suggest that dehydration and/or the activation of visceral afferent inputs may contribute to the elevation of plasma AVP and the upregulation of AVP gene expression in the PVN and the SON of the Li-induced diabetes insipidus rat.","[{'text': 'vasopressin', 'type': 'Chemical', 'start': 34, 'end': 45, 'mesh': 'D014667'}, {'text': 'lithium', 'type': 'Chemical', 'start': 103, 'end': 110, 'mesh': 'D008094'}, {'text': 'diabetes insipidus', 'type': 'Disease', 'start': 119, 'end': 137, 'mesh': 'D003919'}, {'text': 'arginine vasopressin', 'type': 'Chemical', 'start': 161, 'end': 181, 'mesh': 'D001127'}, {'text': 'AVP', 'type': 'Chemical', 'start': 183, 'end': 186, 'mesh': 'D001127'}, {'text': 'lithium', 'type': 'Chemical', 'start': 280, 'end': 287, 'mesh': 'D008094'}, {'text': 'Li', 'type': 'Chemical', 'start': 289, 'end': 291, 'mesh': 'D008094'}, {'text': 'polyuria', 'type': 'Disease', 'start': 301, 'end': 309, 'mesh': 'D011141'}, {'text': 'LiCl', 'type': 'Chemical', 'start': 429, 'end': 433, 'mesh': 'D018021'}, {'text': 'polyuria', 'type': 'Disease', 'start': 476, 'end': 484, 'mesh': 'D011141'}, {'text': 'Li', 'type': 'Chemical', 'start': 490, 'end': 492, 'mesh': 'D008094'}, {'text': 'sodium', 'type': 'Chemical', 'start': 587, 'end': 593, 'mesh': 'D012964'}, {'text': 'Li', 'type': 'Chemical', 'start': 652, 'end': 654, 'mesh': 'D008094'}, {'text': 'AVP', 'type': 'Chemical', 'start': 725, 'end': 728, 'mesh': 'D001127'}, {'text': 'AVP', 'type': 'Chemical', 'start': 748, 'end': 751, 'mesh': 'D001127'}, {'text': 'Li', 'type': 'Chemical', 'start': 812, 'end': 814, 'mesh': 'D008094'}, {'text': 'dehydration', 'type': 'Disease', 'start': 879, 'end': 890, 'mesh': 'D003681'}, {'text': 'AVP', 'type': 'Chemical', 'start': 983, 'end': 986, 'mesh': 'D001127'}, {'text': 'AVP', 'type': 'Chemical', 'start': 1011, 'end': 1014, 'mesh': 'D001127'}, {'text': 'Li', 'type': 'Chemical', 'start': 1061, 'end': 1063, 'mesh': 'D008094'}, {'text': 'diabetes insipidus', 'type': 'Disease', 'start': 1072, 'end': 1090, 'mesh': 'D003919'}]"
+125,9587734,Suxamethonium-induced cardiac arrest and death following 5 days of immobilization.,"The present report describes a case of cardiac arrest and subsequent death as a result of hyperkalaemia following the use of suxamethonium in a 23-year-old Malawian woman. Five days after the onset of the symptoms of meningitis, the patient aspirated stomach contents and needed endotracheal intubation. Forty seconds after injection of suxamethonium, bradycardia and cardiac arrest occurred. Attempts to resuscitate the patient were not successful. The serum level of potassium was observed to be 8.4 mequiv L-1. Apart from the reduction in the patient's level of consciousness, there were no signs of motor neurone damage or of any of the other known predisposing conditions for hyperkalaemia following the administration of suxamethonium. It is postulated that her death was caused by hypersensitivity to suxamethonium, associated with her 5-day immobilization.","[{'text': 'Suxamethonium', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'D013390'}, {'text': 'cardiac arrest', 'type': 'Disease', 'start': 22, 'end': 36, 'mesh': 'D006323'}, {'text': 'death', 'type': 'Disease', 'start': 41, 'end': 46, 'mesh': 'D003643'}, {'text': 'cardiac arrest', 'type': 'Disease', 'start': 122, 'end': 136, 'mesh': 'D006323'}, {'text': 'death', 'type': 'Disease', 'start': 152, 'end': 157, 'mesh': 'D003643'}, {'text': 'hyperkalaemia', 'type': 'Disease', 'start': 173, 'end': 186, 'mesh': 'D006947'}, {'text': 'suxamethonium', 'type': 'Chemical', 'start': 208, 'end': 221, 'mesh': 'D013390'}, {'text': 'meningitis', 'type': 'Disease', 'start': 300, 'end': 310, 'mesh': 'D008581'}, {'text': 'suxamethonium', 'type': 'Chemical', 'start': 420, 'end': 433, 'mesh': 'D013390'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 435, 'end': 446, 'mesh': 'D001919'}, {'text': 'cardiac arrest', 'type': 'Disease', 'start': 451, 'end': 465, 'mesh': 'D006323'}, {'text': 'potassium', 'type': 'Chemical', 'start': 552, 'end': 561, 'mesh': 'D011188'}, {'text': 'hyperkalaemia', 'type': 'Disease', 'start': 764, 'end': 777, 'mesh': 'D006947'}, {'text': 'suxamethonium', 'type': 'Chemical', 'start': 810, 'end': 823, 'mesh': 'D013390'}, {'text': 'death', 'type': 'Disease', 'start': 851, 'end': 856, 'mesh': 'D003643'}, {'text': 'hypersensitivity', 'type': 'Disease', 'start': 871, 'end': 887, 'mesh': 'D004342'}, {'text': 'suxamethonium', 'type': 'Chemical', 'start': 891, 'end': 904, 'mesh': 'D013390'}]"
+126,9698967,An unusual toxic reaction to axillary block by mepivacaine with adrenaline.,"An increase in blood pressure, accompanied by atrial fibrillation, agitation, incomprehensible shouts and loss of consciousness, was observed in an elderly, ASA classification group II, cardiovascularly medicated male, 12 min after performance of axillary block with mepivacaine 850 mg containing adrenaline 0.225 mg, for correction of Dupuytren's contracture. After intravenous administration of labetalol, metoprolol and midazolam the patient's condition improved, and 15 min later he woke up. The block was successful and surgery was conducted as scheduled despite persisting atrial fibrillation. Postoperatively, the patient refused DC cardioversion and was treated medically. Both the temporal relationship of events and the response to treatment suggest that a rapid systemic absorption of mepivacaine with adrenaline and/or interaction of these drugs with the patient's cardiovascular medications were responsible for the perioperative complications.","[{'text': 'mepivacaine', 'type': 'Chemical', 'start': 47, 'end': 58, 'mesh': 'D008619'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 64, 'end': 74, 'mesh': 'D004837'}, {'text': 'increase in blood pressure', 'type': 'Disease', 'start': 79, 'end': 105, 'mesh': 'D006973'}, {'text': 'atrial fibrillation', 'type': 'Disease', 'start': 122, 'end': 141, 'mesh': 'D001281'}, {'text': 'agitation', 'type': 'Disease', 'start': 143, 'end': 152, 'mesh': 'D011595'}, {'text': 'incomprehensible shouts', 'type': 'Disease', 'start': 154, 'end': 177, 'mesh': 'D019954'}, {'text': 'loss of consciousness', 'type': 'Disease', 'start': 182, 'end': 203, 'mesh': 'D014474'}, {'text': 'mepivacaine', 'type': 'Chemical', 'start': 343, 'end': 354, 'mesh': 'D008619'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 373, 'end': 383, 'mesh': 'D004837'}, {'text': ""Dupuytren's contracture"", 'type': 'Disease', 'start': 412, 'end': 435, 'mesh': 'D004387'}, {'text': 'labetalol', 'type': 'Chemical', 'start': 473, 'end': 482, 'mesh': 'D007741'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 484, 'end': 494, 'mesh': 'D008790'}, {'text': 'midazolam', 'type': 'Chemical', 'start': 499, 'end': 508, 'mesh': 'D008874'}, {'text': 'atrial fibrillation', 'type': 'Disease', 'start': 655, 'end': 674, 'mesh': 'D001281'}, {'text': 'mepivacaine', 'type': 'Chemical', 'start': 872, 'end': 883, 'mesh': 'D008619'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 889, 'end': 899, 'mesh': 'D004837'}]"
+127,9855119,Clinical and histopathologic examination of renal allografts treated with tacrolimus (FK506) for at least one year.,"BACKGROUND: We clinically and pathologically analyzed renal allografts from 1 9 renal transplant patients treated with tacrolimus (FK506) for more than 1 year. METHODS: Twenty-six renal allograft biopsy specimens from 1 9 renal transplant patients who underwent transplantations between 1991 and 1993 were evaluated. Thirteen biopsies were performed from stable functioning renal allografts with informed consent (nonepisode biopsy) and the other 13 were from dysfunctional renal allografts with a clinical indication for biopsy (episode biopsy). RESULTS: The main pathologic diagnoses (some overlap) were acute rejection (AR; n = 4), chronic rejection (CR; n=5), AR+CR (n =4), recurrent IgA nephropathy (n =5), normal findings (n =2), minimal-type chronic FK506 nephropathy (n = 9), and mild-type FK506 nephropathy (n = 11). Of the nonepisode biopsies, 7 and 4 biopsies showed minimal-type and mild-type chronic FK506 nephropathy, respectively. Chronic FK506 nephropathy consisted of rough and foamy tubular vacuolization (5 biopsies), arteriolopathy (angiodegeneration of the arteriolar wall; 20 biopsies), focal segmental glomerulosclerosis (4 biopsies) and the striped form of interstitial fibrosis (11 biopsies). The serum creatinine levels of patients in the mild-type chronic FK506 nephropathy group, which included 7 episode biopsies, were statistically higher than those in the minimum-type chronic FK506-nephropathy group (P< 0.001). CONCLUSIONS: This study demonstrates that chronic FK506 nephropathy consists primarily of arteriolopathy manifesting as insudative hyalinosis of the arteriolar wall, and suggests that mild-type chronic FK506 nephropathy is a condition which may lead to deterioration of renal allograft function.","[{'text': 'tacrolimus', 'type': 'Chemical', 'start': 74, 'end': 84, 'mesh': 'D016559'}, {'text': 'FK506', 'type': 'Chemical', 'start': 86, 'end': 91, 'mesh': 'D016559'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 235, 'end': 245, 'mesh': 'D016559'}, {'text': 'FK506', 'type': 'Chemical', 'start': 247, 'end': 252, 'mesh': 'D016559'}, {'text': 'IgA nephropathy', 'type': 'Disease', 'start': 804, 'end': 819, 'mesh': 'D005922'}, {'text': 'FK506', 'type': 'Chemical', 'start': 873, 'end': 878, 'mesh': 'D016559'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 879, 'end': 890, 'mesh': 'D007674'}, {'text': 'FK506', 'type': 'Chemical', 'start': 914, 'end': 919, 'mesh': 'D016559'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 920, 'end': 931, 'mesh': 'D007674'}, {'text': 'FK506', 'type': 'Chemical', 'start': 1029, 'end': 1034, 'mesh': 'D016559'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1035, 'end': 1046, 'mesh': 'D007674'}, {'text': 'FK506', 'type': 'Chemical', 'start': 1070, 'end': 1075, 'mesh': 'D016559'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1076, 'end': 1087, 'mesh': 'D007674'}, {'text': 'focal segmental glomerulosclerosis', 'type': 'Disease', 'start': 1225, 'end': 1259, 'mesh': 'D005923'}, {'text': 'interstitial fibrosis', 'type': 'Disease', 'start': 1297, 'end': 1318, 'mesh': 'D005355'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1344, 'end': 1354, 'mesh': 'D003404'}, {'text': 'FK506', 'type': 'Chemical', 'start': 1399, 'end': 1404, 'mesh': 'D016559'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1405, 'end': 1416, 'mesh': 'D007674'}, {'text': 'FK506', 'type': 'Chemical', 'start': 1524, 'end': 1529, 'mesh': 'D016559'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1530, 'end': 1541, 'mesh': 'D007674'}, {'text': 'FK506', 'type': 'Chemical', 'start': 1610, 'end': 1615, 'mesh': 'D016559'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1616, 'end': 1627, 'mesh': 'D007674'}, {'text': 'FK506', 'type': 'Chemical', 'start': 1762, 'end': 1767, 'mesh': 'D016559'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1768, 'end': 1779, 'mesh': 'D007674'}]"
+128,9869257,Memory facilitation and stimulation of endogenous nerve growth factor synthesis by the acetylcholine releaser PG-9.,"The effects of PG-9 (3alpha-tropyl 2-(p-bromophenyl)propionate), the acetylcholine releaser, on memory processes and nerve growth factor (NGF) synthesis were evaluated. In the mouse passive-avoidance test, PG-9 (10-30 mg/kg, i.p.), administered 20 min before the training session, prevented amnesia induced by both the non selective antimuscarinic drug scopolamine and the M1-selective antagonist S-(-)-ET-126. In the same experimental conditions, PG-9 (5-20 microg per mouse, i.c.v.) was also able to prevent antimuscarine-induced amnesia, demonstrating a central localization of the activity. At the highest effective doses, PG-9 did not produce any collateral symptoms as revealed by the Irwin test, and it did not modify spontaneous motility and inspection activity, as revealed by the hole-board test. PG-9 was also able to increase the amount of NGF secreted in vitro by astrocytes in a dose-dependent manner. The maximal NGF contents obtained by PG-9 were 17.6-fold of the control value. During culture, no morphological changes were found at effective concentrations of PG-9. The current work indicates the ability of PG-9 to induce beneficial effects on cognitive processes and stimulate activity of NGF synthesis in astroglial cells. Therefore, PG-9 could represent a potential useful drug able to improve the function of impaired cognitive processes.","[{'text': 'acetylcholine', 'type': 'Chemical', 'start': 87, 'end': 100, 'mesh': 'D000109'}, {'text': 'PG-9', 'type': 'Chemical', 'start': 110, 'end': 114, 'mesh': 'C087567'}, {'text': 'PG-9', 'type': 'Chemical', 'start': 131, 'end': 135, 'mesh': 'C087567'}, {'text': '3alpha-tropyl 2-(p-bromophenyl)propionate', 'type': 'Chemical', 'start': 137, 'end': 178, 'mesh': 'C087567'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 185, 'end': 198, 'mesh': 'D000109'}, {'text': 'PG-9', 'type': 'Chemical', 'start': 322, 'end': 326, 'mesh': 'C087567'}, {'text': 'amnesia', 'type': 'Disease', 'start': 407, 'end': 414, 'mesh': 'D000647'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 469, 'end': 480, 'mesh': 'D012601'}, {'text': 'S-(-)-ET-126', 'type': 'Chemical', 'start': 513, 'end': 525, 'mesh': 'C098725'}, {'text': 'PG-9', 'type': 'Chemical', 'start': 564, 'end': 568, 'mesh': 'C087567'}, {'text': 'amnesia', 'type': 'Disease', 'start': 648, 'end': 655, 'mesh': 'D000647'}, {'text': 'PG-9', 'type': 'Chemical', 'start': 743, 'end': 747, 'mesh': 'C087567'}, {'text': 'PG-9', 'type': 'Chemical', 'start': 923, 'end': 927, 'mesh': 'C087567'}, {'text': 'PG-9', 'type': 'Chemical', 'start': 1069, 'end': 1073, 'mesh': 'C087567'}, {'text': 'PG-9', 'type': 'Chemical', 'start': 1194, 'end': 1198, 'mesh': 'C087567'}, {'text': 'PG-9', 'type': 'Chemical', 'start': 1242, 'end': 1246, 'mesh': 'C087567'}, {'text': 'PG-9', 'type': 'Chemical', 'start': 1371, 'end': 1375, 'mesh': 'C087567'}]"
+129,10342929,Angioedema due to ACE inhibitors: common and inadequately diagnosed.,The estimated incidence of angioedema during angiotensin-converting enzyme (ACE) inhibitor treatment is between 1 and 7 per thousand patients. This potentially serious adverse effect is often preceded by minor manifestations that may serve as a warning.,"[{'text': 'Angioedema', 'type': 'Disease', 'start': 0, 'end': 10, 'mesh': 'D000799'}, {'text': 'ACE inhibitors', 'type': 'Chemical', 'start': 18, 'end': 32, 'mesh': 'D000806'}, {'text': 'angioedema', 'type': 'Disease', 'start': 96, 'end': 106, 'mesh': 'D000799'}, {'text': 'angiotensin-converting enzyme (ACE) inhibitor', 'type': 'Chemical', 'start': 114, 'end': 159, 'mesh': 'D000806'}]"
+130,10457883,Recurarization in the recovery room.,"A case of recurarization in the recovery room is reported. Accumulation of atracurium in the intravenous line led to recurarization after flushing the line in the recovery room. A respiratory arrest with severe desaturation and bradycardia occurred. Circumstances leading to this event and the mechanisms enabling a neuromuscular blockade to occur, following the administration of a small dose of relaxant, are discussed.","[{'text': 'atracurium', 'type': 'Chemical', 'start': 112, 'end': 122, 'mesh': 'D001279'}, {'text': 'respiratory arrest', 'type': 'Disease', 'start': 217, 'end': 235, 'mesh': 'D012131'}, {'text': 'desaturation', 'type': 'Disease', 'start': 248, 'end': 260, 'mesh': 'D001049'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 265, 'end': 276, 'mesh': 'D001919'}, {'text': 'neuromuscular blockade', 'type': 'Disease', 'start': 353, 'end': 375, 'mesh': 'D020879'}]"
+131,10739826,Recurrent use of newer oral contraceptives and the risk of venous thromboembolism.,"The epidemiological studies that assessed the risk of venous thromboembolism (VTE) associated with newer oral contraceptives (OC) did not distinguish between patterns of OC use, namely first-time users, repeaters and switchers. Data from a Transnational case-control study were used to assess the risk of VTE for the latter patterns of use, while accounting for duration of use. Over the period 1993-1996, 551 cases of VTE were identified in Germany and the UK along with 2066 controls. Totals of 128 cases and 650 controls were analysed for repeat use and 135 cases and 622 controls for switching patterns. The adjusted rate ratio of VTE for repeat users of third generation OC was 0.6 (95% CI:0.3-1.2) relative to repeat users of second generation pills, whereas it was 1.3 (95% CI:0.7-2.4) for switchers from second to third generation pills relative to switchers from third to second generation pills. We conclude that second and third generation agents are associated with equivalent risks of VTE when the same agent is used repeatedly after interruption periods or when users are switched between the two generations of pills. These analyses suggest that the higher risk observed for the newer OC in other studies may be the result of inadequate comparisons of pill users with different patterns of pill use.","[{'text': 'oral contraceptives', 'type': 'Chemical', 'start': 23, 'end': 42, 'mesh': 'D003276'}, {'text': 'venous thromboembolism', 'type': 'Disease', 'start': 59, 'end': 81, 'mesh': 'D054556'}, {'text': 'venous thromboembolism', 'type': 'Disease', 'start': 137, 'end': 159, 'mesh': 'D054556'}, {'text': 'VTE', 'type': 'Disease', 'start': 161, 'end': 164, 'mesh': 'D054556'}, {'text': 'oral contraceptives', 'type': 'Chemical', 'start': 188, 'end': 207, 'mesh': 'D003276'}, {'text': 'OC', 'type': 'Chemical', 'start': 209, 'end': 211, 'mesh': 'D003276'}, {'text': 'OC', 'type': 'Chemical', 'start': 253, 'end': 255, 'mesh': 'D003276'}, {'text': 'VTE', 'type': 'Disease', 'start': 388, 'end': 391, 'mesh': 'D054556'}, {'text': 'VTE', 'type': 'Disease', 'start': 502, 'end': 505, 'mesh': 'D054556'}, {'text': 'VTE', 'type': 'Disease', 'start': 718, 'end': 721, 'mesh': 'D054556'}, {'text': 'OC', 'type': 'Chemical', 'start': 759, 'end': 761, 'mesh': 'D003276'}, {'text': 'VTE', 'type': 'Disease', 'start': 1081, 'end': 1084, 'mesh': 'D054556'}, {'text': 'OC', 'type': 'Chemical', 'start': 1283, 'end': 1285, 'mesh': 'D003276'}]"
+132,10791295,Development of apomorphine-induced aggressive behavior: comparison of adult male and female Wistar rats.,"The development of apomorphine-induced (1.0 mg/kg s.c. once daily) aggressive behavior of adult male and female Wistar rats obtained from the same breeder was studied in two consecutive sets. In male animals, repeated apomorphine treatment induced a gradual development of aggressive behavior as evidenced by the increased intensity of aggressiveness and shortened latency before the first attack toward the opponent. In female rats, only a weak tendency toward aggressiveness was found. In conclusion, the present study demonstrates gender differences in the development of the apomorphine-induced aggressive behavior and indicates that the female rats do not fill the validation criteria for use in this method.","[{'text': 'apomorphine', 'type': 'Chemical', 'start': 15, 'end': 26, 'mesh': 'D001058'}, {'text': 'aggressive behavior', 'type': 'Disease', 'start': 35, 'end': 54, 'mesh': 'D010554'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 124, 'end': 135, 'mesh': 'D001058'}, {'text': 'aggressive behavior', 'type': 'Disease', 'start': 172, 'end': 191, 'mesh': 'D010554'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 323, 'end': 334, 'mesh': 'D001058'}, {'text': 'aggressive behavior', 'type': 'Disease', 'start': 378, 'end': 397, 'mesh': 'D010554'}, {'text': 'aggressiveness', 'type': 'Disease', 'start': 441, 'end': 455, 'mesh': 'D010554'}, {'text': 'aggressiveness', 'type': 'Disease', 'start': 567, 'end': 581, 'mesh': 'D010554'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 684, 'end': 695, 'mesh': 'D001058'}, {'text': 'aggressive behavior', 'type': 'Disease', 'start': 704, 'end': 723, 'mesh': 'D010554'}]"
+133,11147747,Serotonergic antidepressants and urinary incontinence.,"Many new serotonergic antidepressants have been introduced over the past decade. Although urinary incontinence is listed as one side effect of these drugs in their package inserts there is only one report in the literature. This concerns 2 male patients who experienced incontinence while taking venlafaxine. In the present paper the authors describe 2 female patients who developed incontinence secondary to the selective serotonin reuptake inhibitors paroxetine and sertraline, as well as a third who developed this side effect on venlafaxine. In 2 of the 3 cases the patients were also taking lithium carbonate and beta-blockers, both of which could have contributed to the incontinence. Animal studies suggest that incontinence secondary to serotonergic antidepressants could be mediated by the 5HT4 receptors found on the bladder. Further research is needed to delineate the frequency of this troubling side effect and how best to treat it.","[{'text': 'Serotonergic antidepressants', 'type': 'Chemical', 'start': 0, 'end': 28, 'mesh': 'D018490'}, {'text': 'urinary incontinence', 'type': 'Disease', 'start': 33, 'end': 53, 'mesh': 'D014549'}, {'text': 'serotonergic antidepressants', 'type': 'Chemical', 'start': 64, 'end': 92, 'mesh': 'D018490'}, {'text': 'urinary incontinence', 'type': 'Disease', 'start': 145, 'end': 165, 'mesh': 'D014549'}, {'text': 'incontinence', 'type': 'Disease', 'start': 325, 'end': 337, 'mesh': 'D014549'}, {'text': 'venlafaxine', 'type': 'Chemical', 'start': 351, 'end': 362, 'mesh': 'C047426'}, {'text': 'incontinence', 'type': 'Disease', 'start': 438, 'end': 450, 'mesh': 'D014549'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 478, 'end': 487, 'mesh': 'D012701'}, {'text': 'paroxetine', 'type': 'Chemical', 'start': 508, 'end': 518, 'mesh': 'D017374'}, {'text': 'sertraline', 'type': 'Chemical', 'start': 523, 'end': 533, 'mesh': 'D020280'}, {'text': 'venlafaxine', 'type': 'Chemical', 'start': 588, 'end': 599, 'mesh': 'C047426'}, {'text': 'lithium carbonate', 'type': 'Chemical', 'start': 651, 'end': 668, 'mesh': 'D016651'}, {'text': 'incontinence', 'type': 'Disease', 'start': 732, 'end': 744, 'mesh': 'D014549'}, {'text': 'incontinence', 'type': 'Disease', 'start': 774, 'end': 786, 'mesh': 'D014549'}, {'text': 'serotonergic antidepressants', 'type': 'Chemical', 'start': 800, 'end': 828, 'mesh': 'D018490'}]"
+134,11198499,Hypotension following the initiation of tizanidine in a patient treated with an angiotensin converting enzyme inhibitor for chronic hypertension.,"Centrally acting alpha-2 adrenergic agonists are one of several pharmacologic agents used in the treatment of spasticity related to disorders of the central nervous system. In addition to their effects on spasticity, certain adverse cardiorespiratory effects have been reported. Adults chronically treated with angiotensin converting enzyme inhibitors may have a limited ability to respond to hypotension when the sympathetic response is simultaneously blocked. The authors present a 10-year-old boy chronically treated with lisinopril, an angiotensin converting enzyme inhibitor, to control hypertension who developed hypotension following the addition of tizanidine, an alpha-2 agonist, for the treatment of spasticity. The possible interaction of tizanidine and other antihypertensive agents should be kept in mind when prescribing therapy to treat either hypertension or spasticity in such patients.","[{'text': 'Hypotension', 'type': 'Disease', 'start': 0, 'end': 11, 'mesh': 'D007022'}, {'text': 'tizanidine', 'type': 'Chemical', 'start': 40, 'end': 50, 'mesh': 'C023754'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 80, 'end': 91, 'mesh': 'D000809'}, {'text': 'hypertension', 'type': 'Disease', 'start': 132, 'end': 144, 'mesh': 'D006973'}, {'text': 'spasticity', 'type': 'Disease', 'start': 256, 'end': 266, 'mesh': 'D009128'}, {'text': 'disorders of the central nervous system', 'type': 'Disease', 'start': 278, 'end': 317, 'mesh': 'D002493'}, {'text': 'spasticity', 'type': 'Disease', 'start': 351, 'end': 361, 'mesh': 'D009128'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 457, 'end': 468, 'mesh': 'D000809'}, {'text': 'hypotension', 'type': 'Disease', 'start': 539, 'end': 550, 'mesh': 'D007022'}, {'text': 'lisinopril', 'type': 'Chemical', 'start': 671, 'end': 681, 'mesh': 'D017706'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 686, 'end': 697, 'mesh': 'D000809'}, {'text': 'hypertension', 'type': 'Disease', 'start': 738, 'end': 750, 'mesh': 'D006973'}, {'text': 'hypotension', 'type': 'Disease', 'start': 765, 'end': 776, 'mesh': 'D007022'}, {'text': 'tizanidine', 'type': 'Chemical', 'start': 803, 'end': 813, 'mesh': 'C023754'}, {'text': 'spasticity', 'type': 'Disease', 'start': 856, 'end': 866, 'mesh': 'D009128'}, {'text': 'tizanidine', 'type': 'Chemical', 'start': 896, 'end': 906, 'mesh': 'C023754'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1005, 'end': 1017, 'mesh': 'D006973'}, {'text': 'spasticity', 'type': 'Disease', 'start': 1021, 'end': 1031, 'mesh': 'D009128'}]"
+135,11391224,Peritubular capillary basement membrane reduplication in allografts and native kidney disease: a clinicopathologic study of 278 consecutive renal specimens.,"BACKGROUND: An association has been found between transplant glomerulopathy (TG) and reduplication of peritubular capillary basement membranes (PTCR). Although such an association is of practical and theoretical importance, only one prospective study has tried to confirm it. METHODS: We examined 278 consecutive renal specimens (from 135 transplants and 143 native kidneys) for ultrastructural evidence of PTCR. In addition to renal allografts with TG, we also examined grafts with acute rejection, recurrent glomerulonephritis, chronic allograft nephropathy and stable grafts (""protocol biopsies""). Native kidney specimens included a wide range of glomerulopathies as well as cases of thrombotic microangiopathy, malignant hypertension, acute interstitial nephritis, and acute tubular necrosis. RESULTS: We found PTCR in 14 of 15 cases of TG, in 7 transplant biopsy specimens without TG, and in 13 of 143 native kidney biopsy specimens. These 13 included cases of malignant hypertension, thrombotic microangiopathy, lupus nephritis, Henoch-Schonlein nephritis, crescentic glomerulonephritis, and cocaine-related acute renal failure. Mild PTCR in allografts without TG did not predict renal failure or significant proteinuria after follow-up periods of between 3 months and 1 year. CONCLUSIONS: We conclude that in transplants, there is a strong association between well-developed PTCR and TG, while the significance of mild PTCR and its predictive value in the absence of TG is unclear. PTCR also occurs in certain native kidney diseases, though the association is not as strong as that for TG. We suggest that repeated endothelial injury, including immunologic injury, may be the cause of this lesion both in allografts and native kidneys.","[{'text': 'kidney disease', 'type': 'Disease', 'start': 79, 'end': 93, 'mesh': 'D007674'}, {'text': 'transplant glomerulopathy', 'type': 'Disease', 'start': 207, 'end': 232, 'mesh': 'D007674'}, {'text': 'TG', 'type': 'Disease', 'start': 234, 'end': 236, 'mesh': 'D007674'}, {'text': 'TG', 'type': 'Disease', 'start': 607, 'end': 609, 'mesh': 'D007674'}, {'text': 'glomerulonephritis', 'type': 'Disease', 'start': 667, 'end': 685, 'mesh': 'D005921'}, {'text': 'chronic allograft nephropathy', 'type': 'Disease', 'start': 687, 'end': 716, 'mesh': 'D051436'}, {'text': 'glomerulopathies', 'type': 'Disease', 'start': 807, 'end': 823, 'mesh': 'D007674'}, {'text': 'thrombotic microangiopathy', 'type': 'Disease', 'start': 844, 'end': 870, 'mesh': 'D057049'}, {'text': 'malignant hypertension', 'type': 'Disease', 'start': 872, 'end': 894, 'mesh': 'D006974'}, {'text': 'interstitial nephritis', 'type': 'Disease', 'start': 902, 'end': 924, 'mesh': 'D009395'}, {'text': 'acute tubular necrosis', 'type': 'Disease', 'start': 930, 'end': 952, 'mesh': 'D007683'}, {'text': 'TG', 'type': 'Disease', 'start': 998, 'end': 1000, 'mesh': 'D007674'}, {'text': 'TG', 'type': 'Disease', 'start': 1043, 'end': 1045, 'mesh': 'D007674'}, {'text': 'malignant hypertension', 'type': 'Disease', 'start': 1123, 'end': 1145, 'mesh': 'D006974'}, {'text': 'thrombotic microangiopathy', 'type': 'Disease', 'start': 1147, 'end': 1173, 'mesh': 'D057049'}, {'text': 'lupus nephritis', 'type': 'Disease', 'start': 1175, 'end': 1190, 'mesh': 'D008181'}, {'text': 'Henoch-Schonlein nephritis', 'type': 'Disease', 'start': 1192, 'end': 1218, 'mesh': 'D011695'}, {'text': 'glomerulonephritis', 'type': 'Disease', 'start': 1231, 'end': 1249, 'mesh': 'D005921'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1255, 'end': 1262, 'mesh': 'D003042'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 1271, 'end': 1290, 'mesh': 'D058186'}, {'text': 'TG', 'type': 'Disease', 'start': 1324, 'end': 1326, 'mesh': 'D007674'}, {'text': 'renal failure', 'type': 'Disease', 'start': 1343, 'end': 1356, 'mesh': 'D051437'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1372, 'end': 1383, 'mesh': 'D011507'}, {'text': 'TG', 'type': 'Disease', 'start': 1548, 'end': 1550, 'mesh': 'D007674'}, {'text': 'TG', 'type': 'Disease', 'start': 1631, 'end': 1633, 'mesh': 'D007674'}, {'text': 'kidney diseases', 'type': 'Disease', 'start': 1681, 'end': 1696, 'mesh': 'D007674'}, {'text': 'TG', 'type': 'Disease', 'start': 1750, 'end': 1752, 'mesh': 'D007674'}, {'text': 'endothelial injury', 'type': 'Disease', 'start': 1779, 'end': 1797, 'mesh': 'D014947'}, {'text': 'immunologic injury', 'type': 'Disease', 'start': 1809, 'end': 1827, 'mesh': 'D007154'}]"
+136,11426838,Conformationally restricted analogs of BD1008 and an antisense oligodeoxynucleotide targeting sigma1 receptors produce anti-cocaine effects in mice.,"Cocaine's ability to interact with sigma receptors suggests that these proteins mediate some of its behavioral effects. Therefore, three novel sigma receptor ligands with antagonist activity were evaluated in Swiss Webster mice: BD1018 (3S-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane), BD1063 (1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine), and LR132 (1R,2S-(+)-cis-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl)cyclohexylamine). Competition binding assays demonstrated that all three compounds have high affinities for sigma1 receptors. The three compounds vary in their affinities for sigma2 receptors and exhibit negligible affinities for dopamine, opioid, GABA(A) and NMDA receptors. In behavioral studies, pre-treatment of mice with BD1018, BD1063, or LR132 significantly attenuated cocaine-induced convulsions and lethality. Moreover, post-treatment with LR132 prevented cocaine-induced lethality in a significant proportion of animals. In contrast to the protection provided by the putative antagonists, the well-characterized sigma receptor agonist di-o-tolylguanidine (DTG) and the novel sigma receptor agonist BD1031 (3R-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane) each worsened the behavioral toxicity of cocaine. At doses where alone, they produced no significant effects on locomotion, BD1018, BD1063 and LR132 significantly attenuated the locomotor stimulatory effects of cocaine. To further validate the hypothesis that the anti-cocaine effects of the novel ligands involved antagonism of sigma receptors, an antisense oligodeoxynucleotide against sigma1 receptors was also shown to significantly attenuate the convulsive and locomotor stimulatory effects of cocaine. Together, the data suggests that functional antagonism of sigma receptors is capable of attenuating a number of cocaine-induced behaviors.","[{'text': 'BD1008', 'type': 'Chemical', 'start': 39, 'end': 45, 'mesh': 'C085527'}, {'text': 'oligodeoxynucleotide', 'type': 'Chemical', 'start': 63, 'end': 83, 'mesh': 'D009838'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 124, 'end': 131, 'mesh': 'D003042'}, {'text': 'Cocaine', 'type': 'Chemical', 'start': 149, 'end': 156, 'mesh': 'D003042'}, {'text': 'BD1018', 'type': 'Chemical', 'start': 378, 'end': 384, 'mesh': '-1'}, {'text': '3S-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane', 'type': 'Chemical', 'start': 386, 'end': 450, 'mesh': '-1'}, {'text': 'BD1063', 'type': 'Chemical', 'start': 453, 'end': 459, 'mesh': 'C093337'}, {'text': '1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine', 'type': 'Chemical', 'start': 461, 'end': 511, 'mesh': 'C093337'}, {'text': 'LR132', 'type': 'Chemical', 'start': 518, 'end': 523, 'mesh': '-1'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 819, 'end': 827, 'mesh': 'D004298'}, {'text': 'GABA', 'type': 'Chemical', 'start': 837, 'end': 841, 'mesh': 'D005680'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 849, 'end': 853, 'mesh': 'D016202'}, {'text': 'BD1018', 'type': 'Chemical', 'start': 915, 'end': 921, 'mesh': '-1'}, {'text': 'BD1063', 'type': 'Chemical', 'start': 923, 'end': 929, 'mesh': 'C093337'}, {'text': 'LR132', 'type': 'Chemical', 'start': 934, 'end': 939, 'mesh': '-1'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 965, 'end': 972, 'mesh': 'D003042'}, {'text': 'convulsions', 'type': 'Disease', 'start': 981, 'end': 992, 'mesh': 'D012640'}, {'text': 'LR132', 'type': 'Chemical', 'start': 1038, 'end': 1043, 'mesh': '-1'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1054, 'end': 1061, 'mesh': 'D003042'}, {'text': 'di-o-tolylguanidine', 'type': 'Chemical', 'start': 1234, 'end': 1253, 'mesh': 'C050232'}, {'text': 'DTG', 'type': 'Chemical', 'start': 1255, 'end': 1258, 'mesh': 'C050232'}, {'text': 'BD1031', 'type': 'Chemical', 'start': 1297, 'end': 1303, 'mesh': '-1'}, {'text': '3R-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane', 'type': 'Chemical', 'start': 1305, 'end': 1369, 'mesh': '-1'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1400, 'end': 1408, 'mesh': 'D064420'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1412, 'end': 1419, 'mesh': 'D003042'}, {'text': 'BD1018', 'type': 'Chemical', 'start': 1495, 'end': 1501, 'mesh': '-1'}, {'text': 'BD1063', 'type': 'Chemical', 'start': 1503, 'end': 1509, 'mesh': 'C093337'}, {'text': 'LR132', 'type': 'Chemical', 'start': 1514, 'end': 1519, 'mesh': '-1'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1582, 'end': 1589, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1640, 'end': 1647, 'mesh': 'D003042'}, {'text': 'oligodeoxynucleotide', 'type': 'Chemical', 'start': 1730, 'end': 1750, 'mesh': 'D009838'}, {'text': 'convulsive', 'type': 'Disease', 'start': 1822, 'end': 1832, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1870, 'end': 1877, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1991, 'end': 1998, 'mesh': 'D003042'}]"
+137,11569530,"Pharmacokinetic/pharmacodynamic assessment of the effects of E4031, cisapride, terfenadine and terodiline on monophasic action potential duration in dog.","1. Torsades de pointes (TDP) is a potentially fatal ventricular tachycardia associated with increases in QT interval and monophasic action potential duration (MAPD). TDP is a side-effect that has led to withdrawal of several drugs from the market (e.g. terfenadine and terodiline). 2. The potential of compounds to cause TDP was evaluated by monitoring their effects on MAPD in dog. Four compounds known to increase QT interval and cause TDP were investigated: terfenadine, terodiline, cisapride and E4031. On the basis that only free drug in the systemic circulation will elicit a pharmacological response target, free concentrations in plasma were selected to mimic the free drug exposures in man. Infusion regimens were designed that rapidly achieved and maintained target-free concentrations of these drugs in plasma and data on the relationship between free concentration and changes in MAPD were obtained for these compounds. 3. These data indicate that the free ED50 in plasma for terfenadine (1.9 nM), terodiline (76 nM), cisapride (11 nM) and E4031 (1.9 nM) closely correlate with the free concentration in man causing QT effects. For compounds that have shown TDP in the clinic (terfenadine, terodiline, cisapride) there is little differentiation between the dog ED50 and the efficacious free plasma concentrations in man (< 10-fold) reflecting their limited safety margins. These data underline the need to maximize the therapeutic ratio with respect to TDP in potential development candidates and the importance of using free drug concentrations in pharmacokinetic/pharmacodynamic studies.","[{'text': 'E4031', 'type': 'Chemical', 'start': 61, 'end': 66, 'mesh': 'C063968'}, {'text': 'cisapride', 'type': 'Chemical', 'start': 68, 'end': 77, 'mesh': 'D020117'}, {'text': 'terfenadine', 'type': 'Chemical', 'start': 79, 'end': 90, 'mesh': 'D016593'}, {'text': 'terodiline', 'type': 'Chemical', 'start': 95, 'end': 105, 'mesh': 'C010637'}, {'text': 'Torsades de pointes', 'type': 'Disease', 'start': 157, 'end': 176, 'mesh': 'D016171'}, {'text': 'TDP', 'type': 'Disease', 'start': 178, 'end': 181, 'mesh': 'D016171'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 206, 'end': 229, 'mesh': 'D017180'}, {'text': 'TDP', 'type': 'Disease', 'start': 320, 'end': 323, 'mesh': 'D016171'}, {'text': 'terfenadine', 'type': 'Chemical', 'start': 407, 'end': 418, 'mesh': 'D016593'}, {'text': 'terodiline', 'type': 'Chemical', 'start': 423, 'end': 433, 'mesh': 'C010637'}, {'text': 'TDP', 'type': 'Disease', 'start': 475, 'end': 478, 'mesh': 'D016171'}, {'text': 'TDP', 'type': 'Disease', 'start': 592, 'end': 595, 'mesh': 'D016171'}, {'text': 'terfenadine', 'type': 'Chemical', 'start': 615, 'end': 626, 'mesh': 'D016593'}, {'text': 'terodiline', 'type': 'Chemical', 'start': 628, 'end': 638, 'mesh': 'C010637'}, {'text': 'cisapride', 'type': 'Chemical', 'start': 640, 'end': 649, 'mesh': 'D020117'}, {'text': 'E4031', 'type': 'Chemical', 'start': 654, 'end': 659, 'mesh': 'C063968'}, {'text': 'terfenadine', 'type': 'Chemical', 'start': 1142, 'end': 1153, 'mesh': 'D016593'}, {'text': 'terodiline', 'type': 'Chemical', 'start': 1164, 'end': 1174, 'mesh': 'C010637'}, {'text': 'cisapride', 'type': 'Chemical', 'start': 1184, 'end': 1193, 'mesh': 'D020117'}, {'text': 'E4031', 'type': 'Chemical', 'start': 1206, 'end': 1211, 'mesh': 'C063968'}, {'text': 'TDP', 'type': 'Disease', 'start': 1324, 'end': 1327, 'mesh': 'D016171'}, {'text': 'terfenadine', 'type': 'Chemical', 'start': 1343, 'end': 1354, 'mesh': 'D016593'}, {'text': 'terodiline', 'type': 'Chemical', 'start': 1356, 'end': 1366, 'mesh': 'C010637'}, {'text': 'cisapride', 'type': 'Chemical', 'start': 1368, 'end': 1377, 'mesh': 'D020117'}, {'text': 'TDP', 'type': 'Disease', 'start': 1619, 'end': 1622, 'mesh': 'D016171'}]"
+138,11587867,Fatal myeloencephalopathy due to accidental intrathecal vincristin administration: a report of two cases.,"We report on two fatal cases of accidental intrathecal vincristine instillation in a 5-year old girl with recurrent acute lymphoblastic leucemia and a 57-year old man with lymphoblastic lymphoma. The girl died seven days, the man four weeks after intrathecal injection of vincristine. Clinically, the onset was characterized by the signs of opistothonus, sensory and motor dysfunction and ascending paralysis. Histological and immunohistochemical investigations (HE-LFB, CD-68, Neurofilament) revealed degeneration of myelin and axons as well as pseudocystic transformation in areas exposed to vincristine, accompanied by secondary changes with numerous prominent macrophages. The clinical course and histopathological results of the two cases are presented. A review of all reported cases in the literature is given. A better controlled regimen for administering vincristine and intrathecal chemotherapy is recommended.","[{'text': 'myeloencephalopathy', 'type': 'Disease', 'start': 6, 'end': 25, 'mesh': 'D001927'}, {'text': 'vincristin', 'type': 'Chemical', 'start': 56, 'end': 66, 'mesh': 'D014750'}, {'text': 'vincristine', 'type': 'Chemical', 'start': 161, 'end': 172, 'mesh': 'D014750'}, {'text': 'acute lymphoblastic leucemia', 'type': 'Disease', 'start': 222, 'end': 250, 'mesh': 'D054198'}, {'text': 'lymphoblastic lymphoma', 'type': 'Disease', 'start': 278, 'end': 300, 'mesh': 'D054198'}, {'text': 'vincristine', 'type': 'Chemical', 'start': 378, 'end': 389, 'mesh': 'D014750'}, {'text': 'paralysis', 'type': 'Disease', 'start': 505, 'end': 514, 'mesh': 'D010243'}, {'text': 'pseudocystic transformation', 'type': 'Disease', 'start': 652, 'end': 679, 'mesh': '-1'}, {'text': 'vincristine', 'type': 'Chemical', 'start': 700, 'end': 711, 'mesh': 'D014750'}, {'text': 'vincristine', 'type': 'Chemical', 'start': 970, 'end': 981, 'mesh': 'D014750'}]"
+139,11679859,"Intravenous administration of prochlorperazine by 15-minute infusion versus 2-minute bolus does not affect the incidence of akathisia: a prospective, randomized, controlled trial.","STUDY OBJECTIVE: We sought to compare the rate of akathisia after administration of intravenous prochlorperazine as a 2-minute bolus or 15-minute infusion. METHODS: We conducted a prospective, randomized, double-blind study in the emergency department of a central-city teaching hospital. Patients aged 18 years or older treated with prochlorperazine for headache, nausea, or vomiting were eligible for inclusion. Study participants were randomized to receive 10 mg of prochlorperazine administered intravenously by means of 2-minute push (bolus group) or 10 mg diluted in 50 mL of normal saline solution administered by means of intravenous infusion during a 15-minute period (infusion group). The main outcome was the number of study participants experiencing akathisia within 60 minutes of administration. Akathisia was defined as either a spontaneous report of restlessness or agitation or a change of 2 or more in the patient-reported akathisia rating scale and a change of at least 1 in the investigator-observed akathisia rating scale. The intensity of headache and nausea was measured with a 100-mm visual analog scale. RESULTS: One hundred patients were enrolled. One study participant was excluded after protocol violation. Seventy-three percent (73/99) of the study participants were treated for headache and 70% (70/99) for nausea. In the bolus group, 26.0% (13/50) had akathisia compared with 32.7% (16/49) in the infusion group (Delta=-6.7%; 95% confidence interval [CI] -24.6% to 11.2%). The difference between the bolus and infusion groups in the percentage of participants who saw a 50% reduction in their headache intensity within 30 minutes was 11.8% (95% CI -9.6% to 33.3%). The difference in the percentage of patients with a 50% reduction in their nausea was 12.6% (95% CI -4.6% to 29.8%). CONCLUSION: A 50% reduction in the incidence of akathisia when prochlorperazine was administered by means of 15-minute intravenous infusion versus a 2-minute intravenous push was not detected. The efficacy of prochlorperazine in the treatment of headache and nausea likewise did not appear to be affected by the rate of administration, although no formal statistical comparisons were made.","[{'text': 'prochlorperazine', 'type': 'Chemical', 'start': 30, 'end': 46, 'mesh': 'D011346'}, {'text': 'akathisia', 'type': 'Disease', 'start': 124, 'end': 133, 'mesh': 'D017109'}, {'text': 'akathisia', 'type': 'Disease', 'start': 230, 'end': 239, 'mesh': 'D017109'}, {'text': 'prochlorperazine', 'type': 'Chemical', 'start': 276, 'end': 292, 'mesh': 'D011346'}, {'text': 'prochlorperazine', 'type': 'Chemical', 'start': 514, 'end': 530, 'mesh': 'D011346'}, {'text': 'headache', 'type': 'Disease', 'start': 535, 'end': 543, 'mesh': 'D006261'}, {'text': 'nausea', 'type': 'Disease', 'start': 545, 'end': 551, 'mesh': 'D009325'}, {'text': 'vomiting', 'type': 'Disease', 'start': 556, 'end': 564, 'mesh': 'D014839'}, {'text': 'prochlorperazine', 'type': 'Chemical', 'start': 649, 'end': 665, 'mesh': 'D011346'}, {'text': 'akathisia', 'type': 'Disease', 'start': 942, 'end': 951, 'mesh': 'D017109'}, {'text': 'agitation', 'type': 'Disease', 'start': 1061, 'end': 1070, 'mesh': 'D011595'}, {'text': 'akathisia', 'type': 'Disease', 'start': 1120, 'end': 1129, 'mesh': 'D017109'}, {'text': 'akathisia', 'type': 'Disease', 'start': 1199, 'end': 1208, 'mesh': 'D017109'}, {'text': 'headache', 'type': 'Disease', 'start': 1240, 'end': 1248, 'mesh': 'D006261'}, {'text': 'nausea', 'type': 'Disease', 'start': 1253, 'end': 1259, 'mesh': 'D009325'}, {'text': 'headache', 'type': 'Disease', 'start': 1487, 'end': 1495, 'mesh': 'D006261'}, {'text': 'nausea', 'type': 'Disease', 'start': 1516, 'end': 1522, 'mesh': 'D009325'}, {'text': 'akathisia', 'type': 'Disease', 'start': 1562, 'end': 1571, 'mesh': 'D017109'}, {'text': 'headache', 'type': 'Disease', 'start': 1803, 'end': 1811, 'mesh': 'D006261'}, {'text': 'nausea', 'type': 'Disease', 'start': 1950, 'end': 1956, 'mesh': 'D009325'}, {'text': 'akathisia', 'type': 'Disease', 'start': 2040, 'end': 2049, 'mesh': 'D017109'}, {'text': 'prochlorperazine', 'type': 'Chemical', 'start': 2055, 'end': 2071, 'mesh': 'D011346'}, {'text': 'prochlorperazine', 'type': 'Chemical', 'start': 2201, 'end': 2217, 'mesh': 'D011346'}, {'text': 'headache', 'type': 'Disease', 'start': 2238, 'end': 2246, 'mesh': 'D006261'}, {'text': 'nausea', 'type': 'Disease', 'start': 2251, 'end': 2257, 'mesh': 'D009325'}]"
+140,12041669,Antithymocyte globulin in the treatment of D-penicillamine-induced aplastic anemia.,"A patient who received antithymocyte globulin therapy for aplastic anemia due to D-penicillamine therapy is described. Bone marrow recovery and peripheral blood recovery were complete 1 month and 3 months, respectively, after treatment, and blood transfusion or other therapies were not necessary in a follow-up period of more than 2 years. Use of antithymocyte globulin may be the optimal treatment of D-penicillamine-induced aplastic anemia.","[{'text': 'Antithymocyte globulin', 'type': 'Chemical', 'start': 0, 'end': 22, 'mesh': 'D000961'}, {'text': 'D-penicillamine', 'type': 'Chemical', 'start': 43, 'end': 58, 'mesh': 'D010396'}, {'text': 'aplastic anemia', 'type': 'Disease', 'start': 67, 'end': 82, 'mesh': 'D000741'}, {'text': 'antithymocyte globulin', 'type': 'Chemical', 'start': 107, 'end': 129, 'mesh': 'D000961'}, {'text': 'aplastic anemia', 'type': 'Disease', 'start': 142, 'end': 157, 'mesh': 'D000741'}, {'text': 'D-penicillamine', 'type': 'Chemical', 'start': 165, 'end': 180, 'mesh': 'D010396'}, {'text': 'antithymocyte globulin', 'type': 'Chemical', 'start': 432, 'end': 454, 'mesh': 'D000961'}, {'text': 'D-penicillamine', 'type': 'Chemical', 'start': 487, 'end': 502, 'mesh': 'D010396'}, {'text': 'aplastic anemia', 'type': 'Disease', 'start': 511, 'end': 526, 'mesh': 'D000741'}]"
+141,12198388,The relationship between hippocampal acetylcholine release and cholinergic convulsant sensitivity in withdrawal seizure-prone and withdrawal seizure-resistant selected mouse lines.,"BACKGROUND: The septo-hippocampal cholinergic pathway has been implicated in epileptogenesis, and genetic factors influence the response to cholinergic agents, but limited data are available on cholinergic involvement in alcohol withdrawal severity. Thus, the relationship between cholinergic activity and responsiveness and alcohol withdrawal was investigated in a genetic animal model of ethanol withdrawal severity. METHODS: Cholinergic convulsant sensitivity was examined in alcohol-na  ve Withdrawal Seizure-Prone (WSP) and-Resistant (WSR) mice. Animals were administered nicotine, carbachol, or neostigmine via timed tail vein infusion, and the latencies to onset of tremor and clonus were recorded and converted to threshold dose. We also used microdialysis to measure basal and potassium-stimulated acetylcholine (ACh) release in the CA1 region of the hippocampus. Potassium was applied by reverse dialysis twice, separated by 75 min. Hippocampal ACh also was measured during testing for handling-induced convulsions. RESULTS: Sensitivity to several convulsion endpoints induced by nicotine, carbachol, and neostigmine were significantly greater in WSR versus WSP mice. In microdialysis experiments, the lines did not differ in basal release of ACh, and 50 mM KCl increased ACh output in both lines of mice. However, the increase in release of ACh produced by the first application of KCl was 2-fold higher in WSP versus WSR mice. When hippocampal ACh was measured during testing for handling-induced convulsions, extracellular ACh was significantly elevated (192%) in WSP mice, but was nonsignificantly elevated (59%) in WSR mice. CONCLUSIONS: These results suggest that differences in cholinergic activity and postsynaptic sensitivity to cholinergic convulsants may be associated with ethanol withdrawal severity and implicate cholinergic mechanisms in alcohol withdrawal. Specifically, WSP mice may have lower sensitivity to cholinergic convulsants compared with WSR because of postsynaptic receptor desensitization brought on by higher activity of cholinergic neurons.","[{'text': 'acetylcholine', 'type': 'Chemical', 'start': 37, 'end': 50, 'mesh': 'D000109'}, {'text': 'seizure', 'type': 'Disease', 'start': 112, 'end': 119, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 141, 'end': 148, 'mesh': 'D012640'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 402, 'end': 409, 'mesh': 'D000431'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 506, 'end': 513, 'mesh': 'D000431'}, {'text': 'ethanol', 'type': 'Chemical', 'start': 571, 'end': 578, 'mesh': 'D000431'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 660, 'end': 667, 'mesh': 'D000431'}, {'text': 'Seizure', 'type': 'Disease', 'start': 686, 'end': 693, 'mesh': 'D012640'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 758, 'end': 766, 'mesh': 'D009538'}, {'text': 'carbachol', 'type': 'Chemical', 'start': 768, 'end': 777, 'mesh': 'D002217'}, {'text': 'neostigmine', 'type': 'Chemical', 'start': 782, 'end': 793, 'mesh': 'D009388'}, {'text': 'tremor', 'type': 'Disease', 'start': 854, 'end': 860, 'mesh': 'D014202'}, {'text': 'potassium', 'type': 'Chemical', 'start': 967, 'end': 976, 'mesh': 'D011188'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 988, 'end': 1001, 'mesh': 'D000109'}, {'text': 'ACh', 'type': 'Chemical', 'start': 1003, 'end': 1006, 'mesh': 'D000109'}, {'text': 'Potassium', 'type': 'Chemical', 'start': 1054, 'end': 1063, 'mesh': 'D011188'}, {'text': 'ACh', 'type': 'Chemical', 'start': 1136, 'end': 1139, 'mesh': 'D000109'}, {'text': 'convulsions', 'type': 'Disease', 'start': 1194, 'end': 1205, 'mesh': 'D012640'}, {'text': 'convulsion', 'type': 'Disease', 'start': 1239, 'end': 1249, 'mesh': 'D012640'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 1271, 'end': 1279, 'mesh': 'D009538'}, {'text': 'carbachol', 'type': 'Chemical', 'start': 1281, 'end': 1290, 'mesh': 'D002217'}, {'text': 'neostigmine', 'type': 'Chemical', 'start': 1296, 'end': 1307, 'mesh': 'D009388'}, {'text': 'ACh', 'type': 'Chemical', 'start': 1434, 'end': 1437, 'mesh': 'D000109'}, {'text': 'KCl', 'type': 'Chemical', 'start': 1449, 'end': 1452, 'mesh': 'C522374'}, {'text': 'ACh', 'type': 'Chemical', 'start': 1463, 'end': 1466, 'mesh': 'D000109'}, {'text': 'ACh', 'type': 'Chemical', 'start': 1533, 'end': 1536, 'mesh': 'D000109'}, {'text': 'KCl', 'type': 'Chemical', 'start': 1574, 'end': 1577, 'mesh': 'C522374'}, {'text': 'ACh', 'type': 'Chemical', 'start': 1637, 'end': 1640, 'mesh': 'D000109'}, {'text': 'convulsions', 'type': 'Disease', 'start': 1690, 'end': 1701, 'mesh': 'D012640'}, {'text': 'ACh', 'type': 'Chemical', 'start': 1717, 'end': 1720, 'mesh': 'D000109'}, {'text': 'convulsants', 'type': 'Disease', 'start': 1941, 'end': 1952, 'mesh': 'D012640'}, {'text': 'ethanol', 'type': 'Chemical', 'start': 1976, 'end': 1983, 'mesh': 'D000431'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 2044, 'end': 2051, 'mesh': 'D000431'}, {'text': 'convulsants', 'type': 'Disease', 'start': 2129, 'end': 2140, 'mesh': 'D012640'}]"
+142,12574103,Prenatal dexamethasone programs hypertension and renal injury in the rat.,"Dexamethasone is frequently administered to the developing fetus to accelerate pulmonary development. The purpose of the present study was to determine if prenatal dexamethasone programmed a progressive increase in blood pressure and renal injury in rats. Pregnant rats were given either vehicle or 2 daily intraperitoneal injections of dexamethasone (0.2 mg/kg body weight) on gestational days 11 and 12, 13 and 14, 15 and 16, 17 and 18, or 19 and 20. Offspring of rats administered dexamethasone on days 15 and 16 gestation had a 20% reduction in glomerular number compared with control at 6 to 9 months of age (22 527+/-509 versus 28 050+/-561, P<0.05), which was comparable to the percent reduction in glomeruli measured at 3 weeks of age. Six- to 9-month old rats receiving prenatal dexamethasone on days 17 and 18 of gestation had a 17% reduction in glomeruli (23 380+/-587) compared with control rats (P<0.05). Male rats that received prenatal dexamethasone on days 15 and 16, 17 and 18, and 13 and 14 of gestation had elevated blood pressures at 6 months of age; the latter group did not have a reduction in glomerular number. Adult rats given dexamethasone on days 15 and 16 of gestation had more glomeruli with glomerulosclerosis than control rats. This study shows that prenatal dexamethasone in rats results in a reduction in glomerular number, glomerulosclerosis, and hypertension when administered at specific points during gestation. Hypertension was observed in animals that had a reduction in glomeruli as well as in a group that did not have a reduction in glomerular number, suggesting that a reduction in glomerular number is not the sole cause for the development of hypertension.","[{'text': 'dexamethasone', 'type': 'Chemical', 'start': 9, 'end': 22, 'mesh': 'D003907'}, {'text': 'hypertension', 'type': 'Disease', 'start': 32, 'end': 44, 'mesh': 'D006973'}, {'text': 'renal injury', 'type': 'Disease', 'start': 49, 'end': 61, 'mesh': 'D007674'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 238, 'end': 251, 'mesh': 'D003907'}, {'text': 'increase in blood pressure', 'type': 'Disease', 'start': 277, 'end': 303, 'mesh': 'D006973'}, {'text': 'renal injury', 'type': 'Disease', 'start': 308, 'end': 320, 'mesh': 'D007674'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 411, 'end': 424, 'mesh': 'D003907'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 558, 'end': 571, 'mesh': 'D003907'}, {'text': 'reduction in glomerular number', 'type': 'Disease', 'start': 610, 'end': 640, 'mesh': 'D007674'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 862, 'end': 875, 'mesh': 'D003907'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 1025, 'end': 1038, 'mesh': 'D003907'}, {'text': 'elevated blood pressures', 'type': 'Disease', 'start': 1100, 'end': 1124, 'mesh': 'D006973'}, {'text': 'reduction in glomerular number', 'type': 'Disease', 'start': 1177, 'end': 1207, 'mesh': 'D007674'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 1226, 'end': 1239, 'mesh': 'D003907'}, {'text': 'glomerulosclerosis', 'type': 'Disease', 'start': 1295, 'end': 1313, 'mesh': 'D005921'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 1364, 'end': 1377, 'mesh': 'D003907'}, {'text': 'reduction in glomerular number', 'type': 'Disease', 'start': 1399, 'end': 1429, 'mesh': 'D007674'}, {'text': 'glomerulosclerosis', 'type': 'Disease', 'start': 1431, 'end': 1449, 'mesh': 'D005921'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1455, 'end': 1467, 'mesh': 'D006973'}, {'text': 'Hypertension', 'type': 'Disease', 'start': 1523, 'end': 1535, 'mesh': 'D006973'}, {'text': 'reduction in glomerular number', 'type': 'Disease', 'start': 1636, 'end': 1666, 'mesh': 'D007674'}, {'text': 'reduction in glomerular number', 'type': 'Disease', 'start': 1686, 'end': 1716, 'mesh': 'D007674'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1762, 'end': 1774, 'mesh': 'D006973'}]"
+143,12615818,The risk of venous thromboembolism in women prescribed cyproterone acetate in combination with ethinyl estradiol: a nested cohort analysis and case-control study.,"BACKGROUND: Cyproterone acetate combined with ethinyl estradiol (CPA/EE) is licensed in the UK for the treatment of women with acne and hirsutism and is also a treatment option for polycystic ovary syndrome (PCOS). Previous studies have demonstrated an increased risk of venous thromboembolism (VTE) associated with CPA/EE compared with conventional combined oral contraceptives (COCs). We believe the results of those studies may have been affected by residual confounding. METHODS: Using the General Practice Research Database we conducted a cohort analysis and case-control study nested within a population of women aged between 15 and 39 years with acne, hirsutism or PCOS to estimate the risk of VTE associated with CPA/EE. RESULTS: The age-adjusted incidence rate ratio for CPA/EE versus conventional COCs was 2.20 [95% confidence interval (CI) 1.35-3.58]. Using as the reference group women who were not using oral contraception, had no recent pregnancy or menopausal symptoms, the case-control analysis gave an adjusted odds ratio (OR(adj)) of 7.44 (95% CI 3.67-15.08) for CPA/EE use compared with an OR(adj) of 2.58 (95% CI 1.60-4.18) for use of conventional COCs. CONCLUSIONS: We have demonstrated an increased risk of VTE associated with the use of CPA/EE in women with acne, hirsutism or PCOS although residual confounding by indication cannot be excluded.","[{'text': 'venous thromboembolism', 'type': 'Disease', 'start': 12, 'end': 34, 'mesh': 'D054556'}, {'text': 'cyproterone acetate', 'type': 'Chemical', 'start': 55, 'end': 74, 'mesh': 'D017373'}, {'text': 'ethinyl estradiol', 'type': 'Chemical', 'start': 95, 'end': 112, 'mesh': 'D004997'}, {'text': 'Cyproterone acetate', 'type': 'Chemical', 'start': 175, 'end': 194, 'mesh': 'D017373'}, {'text': 'ethinyl estradiol', 'type': 'Chemical', 'start': 209, 'end': 226, 'mesh': 'D004997'}, {'text': 'CPA', 'type': 'Chemical', 'start': 228, 'end': 231, 'mesh': 'D017373'}, {'text': 'EE', 'type': 'Chemical', 'start': 232, 'end': 234, 'mesh': 'D004997'}, {'text': 'acne', 'type': 'Disease', 'start': 290, 'end': 294, 'mesh': 'D000152'}, {'text': 'hirsutism', 'type': 'Disease', 'start': 299, 'end': 308, 'mesh': 'D006628'}, {'text': 'polycystic ovary syndrome', 'type': 'Disease', 'start': 344, 'end': 369, 'mesh': 'D011085'}, {'text': 'PCOS', 'type': 'Disease', 'start': 371, 'end': 375, 'mesh': 'D011085'}, {'text': 'venous thromboembolism', 'type': 'Disease', 'start': 434, 'end': 456, 'mesh': 'D054556'}, {'text': 'VTE', 'type': 'Disease', 'start': 458, 'end': 461, 'mesh': 'D054556'}, {'text': 'CPA', 'type': 'Chemical', 'start': 479, 'end': 482, 'mesh': 'D017373'}, {'text': 'EE', 'type': 'Chemical', 'start': 483, 'end': 485, 'mesh': 'D004997'}, {'text': 'oral contraceptives', 'type': 'Chemical', 'start': 522, 'end': 541, 'mesh': 'D003276'}, {'text': 'acne', 'type': 'Disease', 'start': 816, 'end': 820, 'mesh': 'D000152'}, {'text': 'hirsutism', 'type': 'Disease', 'start': 822, 'end': 831, 'mesh': 'D006628'}, {'text': 'PCOS', 'type': 'Disease', 'start': 835, 'end': 839, 'mesh': 'D011085'}, {'text': 'VTE', 'type': 'Disease', 'start': 864, 'end': 867, 'mesh': 'D054556'}, {'text': 'CPA', 'type': 'Chemical', 'start': 884, 'end': 887, 'mesh': 'D017373'}, {'text': 'EE', 'type': 'Chemical', 'start': 888, 'end': 890, 'mesh': 'D004997'}, {'text': 'CPA', 'type': 'Chemical', 'start': 943, 'end': 946, 'mesh': 'D017373'}, {'text': 'EE', 'type': 'Chemical', 'start': 947, 'end': 949, 'mesh': 'D004997'}, {'text': 'CPA', 'type': 'Chemical', 'start': 1244, 'end': 1247, 'mesh': 'D017373'}, {'text': 'EE', 'type': 'Chemical', 'start': 1248, 'end': 1250, 'mesh': 'D004997'}, {'text': 'VTE', 'type': 'Disease', 'start': 1392, 'end': 1395, 'mesh': 'D054556'}, {'text': 'CPA', 'type': 'Chemical', 'start': 1423, 'end': 1426, 'mesh': 'D017373'}, {'text': 'EE', 'type': 'Chemical', 'start': 1427, 'end': 1429, 'mesh': 'D004997'}, {'text': 'acne', 'type': 'Disease', 'start': 1444, 'end': 1448, 'mesh': 'D000152'}, {'text': 'hirsutism', 'type': 'Disease', 'start': 1450, 'end': 1459, 'mesh': 'D006628'}, {'text': 'PCOS', 'type': 'Disease', 'start': 1463, 'end': 1467, 'mesh': 'D011085'}]"
+144,12789195,Pseudoacromegaly induced by the long-term use of minoxidil.,"Acromegaly is an endocrine disorder caused by chronic excessive growth hormone secretion from the anterior pituitary gland. Significant disfiguring changes occur as a result of bone, cartilage, and soft tissue hypertrophy, including the thickening of the skin, coarsening of facial features, and cutis verticis gyrata. Pseudoacromegaly, on the other hand, is the presence of similar acromegaloid features in the absence of elevated growth hormone or insulin-like growth factor levels. We present a patient with pseudoacromegaly that resulted from the long-term use of minoxidil at an unusually high dose. This is the first case report of pseudoacromegaly as a side effect of minoxidil use.","[{'text': 'Pseudoacromegaly', 'type': 'Disease', 'start': 0, 'end': 16, 'mesh': 'D004194'}, {'text': 'minoxidil', 'type': 'Chemical', 'start': 49, 'end': 58, 'mesh': 'D008914'}, {'text': 'Acromegaly', 'type': 'Disease', 'start': 60, 'end': 70, 'mesh': 'D000172'}, {'text': 'endocrine disorder', 'type': 'Disease', 'start': 77, 'end': 95, 'mesh': 'D004700'}, {'text': 'hypertrophy', 'type': 'Disease', 'start': 270, 'end': 281, 'mesh': 'D006984'}, {'text': 'cutis verticis gyrata', 'type': 'Disease', 'start': 356, 'end': 377, 'mesh': 'C535610'}, {'text': 'Pseudoacromegaly', 'type': 'Disease', 'start': 379, 'end': 395, 'mesh': 'D004194'}, {'text': 'pseudoacromegaly', 'type': 'Disease', 'start': 571, 'end': 587, 'mesh': 'D004194'}, {'text': 'minoxidil', 'type': 'Chemical', 'start': 628, 'end': 637, 'mesh': 'D008914'}, {'text': 'pseudoacromegaly', 'type': 'Disease', 'start': 698, 'end': 714, 'mesh': 'D004194'}, {'text': 'minoxidil', 'type': 'Chemical', 'start': 735, 'end': 744, 'mesh': 'D008914'}]"
+145,12820454,Combined androgen blockade-induced anemia in prostate cancer patients without bone involvement.,"BACKGROUND: To determine the onset and extent of combined androgen blockade (CAB)-induced anemia in prostate cancer patients without bone involvement. PATIENTS AND METHODS: Forty-two patients with biopsy-proven prostatic adenocarcinoma [26 with stage C (T3N0M0) and 16 with stage D1 (T3N1M0)] were included in this study. All patients received CAB [leuprolide acetate (LHRH-A) 3.75 mg, intramuscularly, every 28 days plus 250 mg flutamide, tid, per Os] and were evaluated for anemia by physical examination and laboratory tests at baseline and 4 subsequent intervals (1, 2, 3 and 6 months post-CAB). Hb, PSA and Testosterone measurements were recorded. Patients with stage D2-3 disease, abnormal hemoglobin level or renal and liver function tests that were higher than the upper limits were excluded from the study. The duration of the study was six months. RESULTS: The mean hemoglobin (Hb) levels were significantly declined in all patients from baseline of 14.2 g/dl to 14.0 g/dl, 13.5 g/dl, 13.2 g/dl and 12.7 g/dl at 1, 2, 3 and 6 months post-CAB, respectively. Severe and clinically evident anemia of Hb < 11 g/dl with clinical symptoms was detected in 6 patients (14.3%). This CAB-induced anemia was normochromic and normocytic. At six months post-CAB, patients with severe anemia had a Hb mean value of 10.2 +/- 0.1 g/dl (X +/- SE), whereas the other patients had mild anemia with Hb mean value of 13.2 +/- 0.17 (X +/- SE). The development of severe anemia at 6 months post-CAB was predictable by the reduction of Hb baseline value of more than 2.5 g/dl after 3 months of CAB (p = 0.01). The development of severe CAB-induced anemia in prostate cancer patients did not correlate with T baseline values (T < 3 ng/ml versus T > or = 3 ng/ml), with age (< 76 yrs versus > or = 76 yrs), and clinical stage (stage C versus stage D1). Severe and clinically evident anemia was easily corrected by subcutaneous injections (3 times/week for 1 month) of recombinant erythropoietin (rHuEPO-beta). CONCLUSION: Our data suggest that rHuEPO-beta correctable CAB-induced anemia occurs in 14.3% of prostate cancer patients after 6 months of therapy.","[{'text': 'anemia', 'type': 'Disease', 'start': 35, 'end': 41, 'mesh': 'D000740'}, {'text': 'prostate cancer', 'type': 'Disease', 'start': 45, 'end': 60, 'mesh': 'D011471'}, {'text': 'anemia', 'type': 'Disease', 'start': 186, 'end': 192, 'mesh': 'D000740'}, {'text': 'prostate cancer', 'type': 'Disease', 'start': 196, 'end': 211, 'mesh': 'D011471'}, {'text': 'prostatic adenocarcinoma', 'type': 'Disease', 'start': 307, 'end': 331, 'mesh': 'D000230'}, {'text': 'leuprolide acetate', 'type': 'Chemical', 'start': 445, 'end': 463, 'mesh': 'D016729'}, {'text': 'LHRH-A', 'type': 'Chemical', 'start': 465, 'end': 471, 'mesh': 'D016729'}, {'text': 'flutamide', 'type': 'Chemical', 'start': 525, 'end': 534, 'mesh': 'D005485'}, {'text': 'anemia', 'type': 'Disease', 'start': 572, 'end': 578, 'mesh': 'D000740'}, {'text': 'Testosterone', 'type': 'Chemical', 'start': 708, 'end': 720, 'mesh': 'D013739'}, {'text': 'anemia', 'type': 'Disease', 'start': 1193, 'end': 1199, 'mesh': 'D000740'}, {'text': 'anemia', 'type': 'Disease', 'start': 1292, 'end': 1298, 'mesh': 'D000740'}, {'text': 'anemia', 'type': 'Disease', 'start': 1377, 'end': 1383, 'mesh': 'D000740'}, {'text': 'anemia', 'type': 'Disease', 'start': 1473, 'end': 1479, 'mesh': 'D000740'}, {'text': 'anemia', 'type': 'Disease', 'start': 1554, 'end': 1560, 'mesh': 'D000740'}, {'text': 'anemia', 'type': 'Disease', 'start': 1730, 'end': 1736, 'mesh': 'D000740'}, {'text': 'prostate cancer', 'type': 'Disease', 'start': 1740, 'end': 1755, 'mesh': 'D011471'}, {'text': 'anemia', 'type': 'Disease', 'start': 1963, 'end': 1969, 'mesh': 'D000740'}, {'text': 'anemia', 'type': 'Disease', 'start': 2160, 'end': 2166, 'mesh': 'D000740'}, {'text': 'prostate cancer', 'type': 'Disease', 'start': 2186, 'end': 2201, 'mesh': 'D011471'}]"
+146,14657095,Reversible dilated cardiomyopathy related to amphotericin B therapy.,We describe a patient who developed dilated cardiomyopathy and clinical congestive heart failure after 2 months of therapy with amphotericin B (AmB) for disseminated coccidioidomycosis. His echocardiographic abnormalities and heart failure resolved after posaconazole was substituted for AmB. It is important to recognize the rare and potentially reversible toxicity of AmB.,"[{'text': 'dilated cardiomyopathy', 'type': 'Disease', 'start': 11, 'end': 33, 'mesh': 'D002311'}, {'text': 'amphotericin B', 'type': 'Chemical', 'start': 45, 'end': 59, 'mesh': 'D000666'}, {'text': 'dilated cardiomyopathy', 'type': 'Disease', 'start': 105, 'end': 127, 'mesh': 'D002311'}, {'text': 'heart failure', 'type': 'Disease', 'start': 152, 'end': 165, 'mesh': 'D006333'}, {'text': 'amphotericin B', 'type': 'Chemical', 'start': 197, 'end': 211, 'mesh': 'D000666'}, {'text': 'AmB', 'type': 'Chemical', 'start': 213, 'end': 216, 'mesh': 'D000666'}, {'text': 'coccidioidomycosis', 'type': 'Disease', 'start': 235, 'end': 253, 'mesh': 'D003047'}, {'text': 'heart failure', 'type': 'Disease', 'start': 295, 'end': 308, 'mesh': 'D006333'}, {'text': 'posaconazole', 'type': 'Chemical', 'start': 324, 'end': 336, 'mesh': 'C101425'}, {'text': 'AmB', 'type': 'Chemical', 'start': 357, 'end': 360, 'mesh': 'D000666'}, {'text': 'toxicity', 'type': 'Disease', 'start': 427, 'end': 435, 'mesh': 'D064420'}, {'text': 'AmB', 'type': 'Chemical', 'start': 439, 'end': 442, 'mesh': 'D000666'}]"
+147,14765563,Risks of the consumption of beverages containing quinine.,"Although the United States Food and Drug Administration banned its use for nocturnal leg cramps due to lack of safety and efficacy, quinine is widely available in beverages including tonic water and bitter lemon. Numerous anecdotal reports suggest that products containing quinine may produce neurological complications, including confusion, altered mental status, seizures, and coma, particularly in older women. Psychologists need to inquire about consumption of quinine-containing beverages as part of an evaluation process.","[{'text': 'quinine', 'type': 'Chemical', 'start': 49, 'end': 56, 'mesh': 'D011803'}, {'text': 'nocturnal leg cramps', 'type': 'Disease', 'start': 133, 'end': 153, 'mesh': 'D020922'}, {'text': 'quinine', 'type': 'Chemical', 'start': 190, 'end': 197, 'mesh': 'D011803'}, {'text': 'quinine', 'type': 'Chemical', 'start': 331, 'end': 338, 'mesh': 'D011803'}, {'text': 'neurological complications', 'type': 'Disease', 'start': 351, 'end': 377, 'mesh': 'D002493'}, {'text': 'confusion', 'type': 'Disease', 'start': 389, 'end': 398, 'mesh': 'D003221'}, {'text': 'seizures', 'type': 'Disease', 'start': 423, 'end': 431, 'mesh': 'D012640'}, {'text': 'coma', 'type': 'Disease', 'start': 437, 'end': 441, 'mesh': 'D003128'}, {'text': 'quinine', 'type': 'Chemical', 'start': 523, 'end': 530, 'mesh': 'D011803'}]"
+148,15036754,Organophosphate-induced convulsions and prevention of neuropathological damages.,"Such organophosphorus (OP) compounds as diisopropylfluorophosphate (DFP), sarin and soman are potent inhibitors of acetylcholinesterases (AChEs) and butyrylcholinesterases (BChEs). The acute toxicity of OPs is the result of their irreversible binding with AChEs in the central nervous system (CNS), which elevates acetylcholine (ACh) levels. The protective action of subcutaneously (SC) administered antidotes or their combinations in DFP (2.0 mg/kg BW) intoxication was studied in 9-10-weeks-old Han-Wistar male rats. The rats received AChE reactivator pralidoxime-2-chloride (2PAM) (30.0 mg/kg BW), anticonvulsant diazepam (2.0 mg/kg BW), A(1)-adenosine receptor agonist N(6)-cyclopentyl adenosine (CPA) (2.0 mg/kg BW), NMDA-receptor antagonist dizocilpine maleate (+-MK801 hydrogen maleate) (2.0 mg/kg BW) or their combinations with cholinolytic drug atropine sulfate (50.0 mg/kg BW) immediately or 30 min after the single SC injection of DFP. The control rats received atropine sulfate, but also saline and olive oil instead of other antidotes and DFP, respectively. All rats were terminated either 24 h or 3 weeks after the DFP injection. The rats treated with DFP-atropine showed severe typical OP-induced toxicity signs. When CPA, diazepam or 2PAM was given immediately after DFP-atropine, these treatments prevented, delayed or shortened the occurrence of serious signs of poisoning. Atropine-MK801 did not offer any additional protection against DFP toxicity. In conclusion, CPA, diazepam and 2PAM in combination with atropine prevented the occurrence of serious signs of poisoning and thus reduced the toxicity of DFP in rat.","[{'text': 'Organophosphate', 'type': 'Chemical', 'start': 0, 'end': 15, 'mesh': 'D010755'}, {'text': 'convulsions', 'type': 'Disease', 'start': 24, 'end': 35, 'mesh': 'D012640'}, {'text': 'neuropathological damages', 'type': 'Disease', 'start': 54, 'end': 79, 'mesh': 'D004194'}, {'text': 'organophosphorus', 'type': 'Chemical', 'start': 86, 'end': 102, 'mesh': 'D010755'}, {'text': 'OP', 'type': 'Chemical', 'start': 104, 'end': 106, 'mesh': 'D010755'}, {'text': 'diisopropylfluorophosphate', 'type': 'Chemical', 'start': 121, 'end': 147, 'mesh': 'D007531'}, {'text': 'DFP', 'type': 'Chemical', 'start': 149, 'end': 152, 'mesh': 'D007531'}, {'text': 'sarin', 'type': 'Chemical', 'start': 155, 'end': 160, 'mesh': 'D012524'}, {'text': 'soman', 'type': 'Chemical', 'start': 165, 'end': 170, 'mesh': 'D012999'}, {'text': 'toxicity', 'type': 'Disease', 'start': 272, 'end': 280, 'mesh': 'D064420'}, {'text': 'OPs', 'type': 'Chemical', 'start': 284, 'end': 287, 'mesh': 'D010755'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 395, 'end': 408, 'mesh': 'D000109'}, {'text': 'ACh', 'type': 'Chemical', 'start': 410, 'end': 413, 'mesh': 'D000109'}, {'text': 'DFP', 'type': 'Chemical', 'start': 516, 'end': 519, 'mesh': 'D007531'}, {'text': 'pralidoxime-2-chloride', 'type': 'Chemical', 'start': 635, 'end': 657, 'mesh': 'D011220'}, {'text': '2PAM', 'type': 'Chemical', 'start': 659, 'end': 663, 'mesh': 'D011220'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 697, 'end': 705, 'mesh': 'D003975'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 727, 'end': 736, 'mesh': 'D000241'}, {'text': 'N(6)-cyclopentyl adenosine', 'type': 'Chemical', 'start': 754, 'end': 780, 'mesh': 'C048599'}, {'text': 'CPA', 'type': 'Chemical', 'start': 782, 'end': 785, 'mesh': 'C048599'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 803, 'end': 807, 'mesh': 'D016202'}, {'text': 'dizocilpine maleate', 'type': 'Chemical', 'start': 828, 'end': 847, 'mesh': 'D016291'}, {'text': 'atropine sulfate', 'type': 'Chemical', 'start': 935, 'end': 951, 'mesh': 'D001285'}, {'text': 'DFP', 'type': 'Chemical', 'start': 1023, 'end': 1026, 'mesh': 'D007531'}, {'text': 'atropine sulfate', 'type': 'Chemical', 'start': 1054, 'end': 1070, 'mesh': 'D001285'}, {'text': 'DFP', 'type': 'Chemical', 'start': 1133, 'end': 1136, 'mesh': 'D007531'}, {'text': 'DFP', 'type': 'Chemical', 'start': 1210, 'end': 1213, 'mesh': 'D007531'}, {'text': 'DFP', 'type': 'Chemical', 'start': 1247, 'end': 1250, 'mesh': 'D007531'}, {'text': 'atropine', 'type': 'Chemical', 'start': 1251, 'end': 1259, 'mesh': 'D001285'}, {'text': 'OP', 'type': 'Chemical', 'start': 1282, 'end': 1284, 'mesh': 'D010755'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1293, 'end': 1301, 'mesh': 'D064420'}, {'text': 'CPA', 'type': 'Chemical', 'start': 1314, 'end': 1317, 'mesh': 'C048599'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 1319, 'end': 1327, 'mesh': 'D003975'}, {'text': '2PAM', 'type': 'Chemical', 'start': 1331, 'end': 1335, 'mesh': 'D011220'}, {'text': 'DFP', 'type': 'Chemical', 'start': 1364, 'end': 1367, 'mesh': 'D007531'}, {'text': 'atropine', 'type': 'Chemical', 'start': 1368, 'end': 1376, 'mesh': 'D001285'}, {'text': 'poisoning', 'type': 'Disease', 'start': 1462, 'end': 1471, 'mesh': 'D011041'}, {'text': 'Atropine', 'type': 'Chemical', 'start': 1473, 'end': 1481, 'mesh': 'D001285'}, {'text': 'MK801', 'type': 'Chemical', 'start': 1482, 'end': 1487, 'mesh': 'D016291'}, {'text': 'DFP', 'type': 'Chemical', 'start': 1536, 'end': 1539, 'mesh': 'D007531'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1540, 'end': 1548, 'mesh': 'D064420'}, {'text': 'CPA', 'type': 'Chemical', 'start': 1565, 'end': 1568, 'mesh': 'C048599'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 1570, 'end': 1578, 'mesh': 'D003975'}, {'text': '2PAM', 'type': 'Chemical', 'start': 1583, 'end': 1587, 'mesh': 'D011220'}, {'text': 'atropine', 'type': 'Chemical', 'start': 1608, 'end': 1616, 'mesh': 'D001285'}, {'text': 'poisoning', 'type': 'Disease', 'start': 1662, 'end': 1671, 'mesh': 'D011041'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1693, 'end': 1701, 'mesh': 'D064420'}, {'text': 'DFP', 'type': 'Chemical', 'start': 1705, 'end': 1708, 'mesh': 'D007531'}]"
+149,15145918,Differential modulation by estrogen of alpha2-adrenergic and I1-imidazoline receptor-mediated hypotension in female rats.,"We have recently shown that estrogen negatively modulates the hypotensive effect of clonidine (mixed alpha2-/I1-receptor agonist) in female rats and implicates the cardiovascular autonomic control in this interaction. The present study investigated whether this effect of estrogen involves interaction with alpha2- and/or I1-receptors. Changes evoked by a single intraperitoneal injection of rilmenidine (600 microg/kg) or alpha-methyldopa (100 mg/kg), selective I1- and alpha2-receptor agonists, respectively, in blood pressure, hemodynamic variability, and locomotor activity were assessed in radiotelemetered sham-operated and ovariectomized (Ovx) Sprague-Dawley female rats with or without 12-wk estrogen replacement. Three time domain indexes of hemodynamic variability were employed: the standard deviation of mean arterial pressure as a measure of blood pressure variability and the standard deviation of beat-to-beat intervals (SDRR) and the root mean square of successive differences in R-wave-to-R-wave intervals as measures of heart rate variability. In sham-operated rats, rilmenidine or alpha-methyldopa elicited similar hypotension that lasted at least 5 h and was associated with reductions in standard deviation of mean arterial pressure. SDRR was reduced only by alpha-methyldopa. Ovx significantly enhanced the hypotensive response to alpha-methyldopa, in contrast to no effect on rilmenidine hypotension. The enhanced alpha-methyldopa hypotension in Ovx rats was paralleled with further reduction in SDRR and a reduced locomotor activity. Estrogen replacement (17beta-estradiol subcutaneous pellet, 14.2 microg/day, 12 wk) of Ovx rats restored the hemodynamic and locomotor effects of alpha-methyldopa to sham-operated levels. These findings suggest that estrogen downregulates alpha2- but not I1-receptor-mediated hypotension and highlight a role for the cardiac autonomic control in alpha-methyldopa-estrogen interaction.","[{'text': 'estrogen', 'type': 'Chemical', 'start': 27, 'end': 35, 'mesh': 'D004967'}, {'text': 'imidazoline', 'type': 'Chemical', 'start': 64, 'end': 75, 'mesh': 'D048288'}, {'text': 'hypotension', 'type': 'Disease', 'start': 94, 'end': 105, 'mesh': 'D007022'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 150, 'end': 158, 'mesh': 'D004967'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 184, 'end': 195, 'mesh': 'D007022'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 206, 'end': 215, 'mesh': 'D003000'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 394, 'end': 402, 'mesh': 'D004967'}, {'text': 'rilmenidine', 'type': 'Chemical', 'start': 514, 'end': 525, 'mesh': 'C032302'}, {'text': 'alpha-methyldopa', 'type': 'Chemical', 'start': 545, 'end': 561, 'mesh': 'D008750'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 822, 'end': 830, 'mesh': 'D004967'}, {'text': 'rilmenidine', 'type': 'Chemical', 'start': 1207, 'end': 1218, 'mesh': 'C032302'}, {'text': 'alpha-methyldopa', 'type': 'Chemical', 'start': 1222, 'end': 1238, 'mesh': 'D008750'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1256, 'end': 1267, 'mesh': 'D007022'}, {'text': 'alpha-methyldopa', 'type': 'Chemical', 'start': 1402, 'end': 1418, 'mesh': 'D008750'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 1451, 'end': 1462, 'mesh': 'D007022'}, {'text': 'alpha-methyldopa', 'type': 'Chemical', 'start': 1475, 'end': 1491, 'mesh': 'D008750'}, {'text': 'rilmenidine', 'type': 'Chemical', 'start': 1521, 'end': 1532, 'mesh': 'C032302'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1533, 'end': 1544, 'mesh': 'D007022'}, {'text': 'alpha-methyldopa', 'type': 'Chemical', 'start': 1559, 'end': 1575, 'mesh': 'D008750'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1576, 'end': 1587, 'mesh': 'D007022'}, {'text': 'a reduced locomotor activity', 'type': 'Disease', 'start': 1650, 'end': 1678, 'mesh': 'D001523'}, {'text': '17beta-estradiol', 'type': 'Chemical', 'start': 1702, 'end': 1718, 'mesh': 'D004958'}, {'text': 'alpha-methyldopa', 'type': 'Chemical', 'start': 1826, 'end': 1842, 'mesh': 'D008750'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 1896, 'end': 1904, 'mesh': 'D004967'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1956, 'end': 1967, 'mesh': 'D007022'}, {'text': 'alpha-methyldopa', 'type': 'Chemical', 'start': 2026, 'end': 2042, 'mesh': 'D008750'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 2043, 'end': 2051, 'mesh': 'D004967'}]"
+150,15233872,Cardioprotective effect of tincture of Crataegus on isoproterenol-induced myocardial infarction in rats.,"Tincture of Crataegus (TCR), an alcoholic extract of the berries of hawthorn (Crataegus oxycantha), is used in herbal and homeopathic medicine. The present study was done to investigate the protective effect of TCR on experimentally induced myocardial infarction in rats. Pretreatment of TCR, at a dose of 0.5 mL/100 g bodyweight per day, orally for 30 days, prevented the increase in lipid peroxidation and activity of marker enzymes observed in isoproterenol-induced rats (85 mg kg(-1) s. c. for 2 days at an interval of 24 h). TCR prevented the isoproterenol-induced decrease in antioxidant enzymes in the heart and increased the rate of ADP-stimulated oxygen uptake and respiratory coupling ratio. TCR protected against pathological changes induced by isoproterenol in rat heart. The results show that pretreatment with TCR may be useful in preventing the damage induced by isoproterenol in rat heart.","[{'text': 'tincture of Crataegus', 'type': 'Chemical', 'start': 27, 'end': 48, 'mesh': 'C007145'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 52, 'end': 65, 'mesh': 'D007545'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 74, 'end': 95, 'mesh': 'D009203'}, {'text': 'Tincture of Crataegus', 'type': 'Chemical', 'start': 105, 'end': 126, 'mesh': 'C007145'}, {'text': 'TCR', 'type': 'Chemical', 'start': 128, 'end': 131, 'mesh': 'C007145'}, {'text': 'alcoholic extract of the berries of hawthorn', 'type': 'Chemical', 'start': 137, 'end': 181, 'mesh': 'C007145'}, {'text': 'Crataegus oxycantha', 'type': 'Chemical', 'start': 183, 'end': 202, 'mesh': 'C007145'}, {'text': 'TCR', 'type': 'Chemical', 'start': 316, 'end': 319, 'mesh': 'C007145'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 346, 'end': 367, 'mesh': 'D009203'}, {'text': 'TCR', 'type': 'Chemical', 'start': 393, 'end': 396, 'mesh': 'C007145'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 552, 'end': 565, 'mesh': 'D007545'}, {'text': 'TCR', 'type': 'Chemical', 'start': 635, 'end': 638, 'mesh': 'C007145'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 653, 'end': 666, 'mesh': 'D007545'}, {'text': 'ADP', 'type': 'Chemical', 'start': 746, 'end': 749, 'mesh': 'D000244'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 761, 'end': 767, 'mesh': 'D010100'}, {'text': 'TCR', 'type': 'Chemical', 'start': 807, 'end': 810, 'mesh': 'C007145'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 861, 'end': 874, 'mesh': 'D007545'}, {'text': 'TCR', 'type': 'Chemical', 'start': 929, 'end': 932, 'mesh': 'C007145'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 983, 'end': 996, 'mesh': 'D007545'}]"
+151,15458908,Safety and adverse effects associated with raloxifene: multiple outcomes of raloxifene evaluation.,"OBJECTIVE: To examine the effect of raloxifene on major adverse events that occur with postmenopausal estrogen therapy or tamoxifen. METHODS: The Multiple Outcomes of Raloxifene Evaluation, a multicenter, randomized, double-blind trial, enrolled 7,705 postmenopausal women with osteoporosis. Women were randomly assigned to raloxifene 60 mg/d or 120 mg/d or placebo. Outcomes included venous thromboembolism, cataracts, gallbladder disease, and endometrial hyperplasia or cancer. RESULTS: During a mean follow-up of 3.3 years, raloxifene was associated with an increased risk for venous thromboembolism (relative risk [RR] 2.1; 95% confidence interval [CI] 1.2-3.8). The excess event rate was 1.8 per 1,000 woman-years (95% CI -0.5-4.1), and the number needed to treat to cause 1 event was 170 (95% CI 100-582) over 3.3 years. Risk in the raloxifene group was higher than in the placebo group for the first 2 years, but decreased to about the same rate as in the placebo group thereafter. Raloxifene did not increase risk for cataracts (RR 0.9; 95% CI 0.8-1.1), gallbladder disease (RR 1.0; 95% CI 0.7-1.3), endometrial hyperplasia (RR 1.3; 95% CI 0.4-5.1), or endometrial cancer (RR 0.9; 95% CI 0.3-2.7). CONCLUSION: Raloxifene was associated with an increased risk for venous thromboembolism, but there was no increased risk for cataracts, gallbladder disease, endometrial hyperplasia, or endometrial cancer. LEVEL OF EVIDENCE: I","[{'text': 'raloxifene', 'type': 'Chemical', 'start': 43, 'end': 53, 'mesh': 'D020849'}, {'text': 'raloxifene', 'type': 'Chemical', 'start': 76, 'end': 86, 'mesh': 'D020849'}, {'text': 'raloxifene', 'type': 'Chemical', 'start': 135, 'end': 145, 'mesh': 'D020849'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 201, 'end': 209, 'mesh': 'D004967'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 221, 'end': 230, 'mesh': 'D013629'}, {'text': 'Raloxifene', 'type': 'Chemical', 'start': 266, 'end': 276, 'mesh': 'D020849'}, {'text': 'osteoporosis', 'type': 'Disease', 'start': 377, 'end': 389, 'mesh': 'D010024'}, {'text': 'raloxifene', 'type': 'Chemical', 'start': 423, 'end': 433, 'mesh': 'D020849'}, {'text': 'venous thromboembolism', 'type': 'Disease', 'start': 484, 'end': 506, 'mesh': 'D054556'}, {'text': 'cataracts', 'type': 'Disease', 'start': 508, 'end': 517, 'mesh': 'D002386'}, {'text': 'gallbladder disease', 'type': 'Disease', 'start': 519, 'end': 538, 'mesh': 'D005705'}, {'text': 'raloxifene', 'type': 'Chemical', 'start': 626, 'end': 636, 'mesh': 'D020849'}, {'text': 'venous thromboembolism', 'type': 'Disease', 'start': 679, 'end': 701, 'mesh': 'D054556'}, {'text': 'raloxifene', 'type': 'Chemical', 'start': 938, 'end': 948, 'mesh': 'D020849'}, {'text': 'Raloxifene', 'type': 'Chemical', 'start': 1088, 'end': 1098, 'mesh': 'D020849'}, {'text': 'cataracts', 'type': 'Disease', 'start': 1125, 'end': 1134, 'mesh': 'D002386'}, {'text': 'gallbladder disease', 'type': 'Disease', 'start': 1161, 'end': 1180, 'mesh': 'D005705'}, {'text': 'endometrial hyperplasia', 'type': 'Disease', 'start': 1207, 'end': 1230, 'mesh': 'D004714'}, {'text': 'endometrial cancer', 'type': 'Disease', 'start': 1260, 'end': 1278, 'mesh': 'D016889'}, {'text': 'Raloxifene', 'type': 'Chemical', 'start': 1317, 'end': 1327, 'mesh': 'D020849'}, {'text': 'venous thromboembolism', 'type': 'Disease', 'start': 1370, 'end': 1392, 'mesh': 'D054556'}, {'text': 'cataracts', 'type': 'Disease', 'start': 1430, 'end': 1439, 'mesh': 'D002386'}, {'text': 'gallbladder disease', 'type': 'Disease', 'start': 1441, 'end': 1460, 'mesh': 'D005705'}, {'text': 'endometrial hyperplasia', 'type': 'Disease', 'start': 1462, 'end': 1485, 'mesh': 'D004714'}, {'text': 'endometrial cancer', 'type': 'Disease', 'start': 1490, 'end': 1508, 'mesh': 'D016889'}]"
+152,15737522,Ceftriaxone-associated biliary pseudolithiasis in paediatric surgical patients.,"It is well known that ceftriaxone leads to pseudolithiasis in some patients. Clinical and experimental studies also suggest that situations causing gallbladder dysfunction, such as fasting, may have a role for the development of pseudolithiasis. In this study, we prospectively evaluated the incidence and clinical importance of pseudolithiasis in paediatric surgical patients receiving ceftriaxone treatment, who often had to fast in the post-operative period. Fifty children who were given ceftriaxone were evaluated by serial abdominal sonograms. Of those, 13 (26%) developed biliary pathology. Comparison of the patients with or without pseudolithiasis revealed no significant difference with respect to age, sex, duration of the treatment and starvation variables. After cessation of the treatment, pseudolithiasis resolved spontaneously within a short period. The incidence of pseudolithiasis is not affected by fasting.","[{'text': 'Ceftriaxone', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D002443'}, {'text': 'biliary pseudolithiasis', 'type': 'Disease', 'start': 23, 'end': 46, 'mesh': 'D001660'}, {'text': 'ceftriaxone', 'type': 'Chemical', 'start': 102, 'end': 113, 'mesh': 'D002443'}, {'text': 'pseudolithiasis', 'type': 'Disease', 'start': 123, 'end': 138, 'mesh': 'D001660'}, {'text': 'gallbladder dysfunction', 'type': 'Disease', 'start': 228, 'end': 251, 'mesh': 'D005705'}, {'text': 'pseudolithiasis', 'type': 'Disease', 'start': 309, 'end': 324, 'mesh': 'D001660'}, {'text': 'pseudolithiasis', 'type': 'Disease', 'start': 409, 'end': 424, 'mesh': 'D001660'}, {'text': 'ceftriaxone', 'type': 'Chemical', 'start': 467, 'end': 478, 'mesh': 'D002443'}, {'text': 'ceftriaxone', 'type': 'Chemical', 'start': 572, 'end': 583, 'mesh': 'D002443'}, {'text': 'pseudolithiasis', 'type': 'Disease', 'start': 721, 'end': 736, 'mesh': 'D001660'}, {'text': 'pseudolithiasis', 'type': 'Disease', 'start': 884, 'end': 899, 'mesh': 'D001660'}, {'text': 'pseudolithiasis', 'type': 'Disease', 'start': 963, 'end': 978, 'mesh': 'D001660'}]"
+153,16005948,Evaluation of the anticocaine monoclonal antibody GNC92H2 as an immunotherapy for cocaine overdose.,"The illicit use of cocaine continues in epidemic proportions and treatment for cocaine overdose remains elusive. Current protein-based technology offers a new therapeutic venue by which antibodies bind the drug in the blood stream, inactivating its toxic effects. The therapeutic potential of the anticocaine antibody GNC92H2 was examined using a model of cocaine overdose. Swiss albino mice prepared with intrajugular catheters were tested in photocell cages after administration of 93 mg/kg (LD50) of cocaine and GNC92H2 infusions ranging from 30 to 190 mg/kg. GNC92H2 was delivered 30 min before, concomitantly or 3 min after cocaine treatment. Significant blockade of cocaine toxicity was observed with the higher dose of GNC92H2 (190 mg/kg), where premorbid behaviors were reduced up to 40%, seizures up to 77% and death by 72%. Importantly, GNC92H2 prevented death even post-cocaine injection. The results support the important potential of GNC92H2 as a therapeutic tool against cocaine overdose.","[{'text': 'GNC92H2', 'type': 'Chemical', 'start': 50, 'end': 57, 'mesh': '-1'}, {'text': 'cocaine overdose', 'type': 'Disease', 'start': 82, 'end': 98, 'mesh': 'D062787'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 119, 'end': 126, 'mesh': 'D003042'}, {'text': 'cocaine overdose', 'type': 'Disease', 'start': 179, 'end': 195, 'mesh': 'D062787'}, {'text': 'GNC92H2', 'type': 'Chemical', 'start': 418, 'end': 425, 'mesh': '-1'}, {'text': 'cocaine overdose', 'type': 'Disease', 'start': 456, 'end': 472, 'mesh': 'D062787'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 603, 'end': 610, 'mesh': 'D003042'}, {'text': 'GNC92H2', 'type': 'Chemical', 'start': 615, 'end': 622, 'mesh': '-1'}, {'text': 'GNC92H2', 'type': 'Chemical', 'start': 663, 'end': 670, 'mesh': '-1'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 729, 'end': 736, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 772, 'end': 779, 'mesh': 'D003042'}, {'text': 'toxicity', 'type': 'Disease', 'start': 780, 'end': 788, 'mesh': 'D064420'}, {'text': 'GNC92H2', 'type': 'Chemical', 'start': 826, 'end': 833, 'mesh': '-1'}, {'text': 'seizures', 'type': 'Disease', 'start': 897, 'end': 905, 'mesh': 'D012640'}, {'text': 'death', 'type': 'Disease', 'start': 920, 'end': 925, 'mesh': 'D003643'}, {'text': 'GNC92H2', 'type': 'Chemical', 'start': 947, 'end': 954, 'mesh': '-1'}, {'text': 'death', 'type': 'Disease', 'start': 965, 'end': 970, 'mesh': 'D003643'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 981, 'end': 988, 'mesh': 'D003042'}, {'text': 'GNC92H2', 'type': 'Chemical', 'start': 1047, 'end': 1054, 'mesh': '-1'}, {'text': 'cocaine overdose', 'type': 'Disease', 'start': 1085, 'end': 1101, 'mesh': 'D062787'}]"
+154,16167916,"The effects of short-term raloxifene therapy on fibrinolysis markers: TAFI, tPA, and PAI-1.","BACKGROUND: Markers of fibrinolysis, thrombin-activatable fibrinolysis inhibitor (TAFI), tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) levels were studied for the evaluation of short-term effects of raloxifene administration in postmenopausal women. METHODS: Thirty-nine postmenopausal women with osteopenia or osteoporosis were included in this prospective, controlled clinical study. Twenty-five women were given raloxifene hydrochloride (60 mg/day) plus calcium (500 mg/day). Age-matched controls (n = 14) were given only calcium. Plasma TAFI, tPA, and PAI-1 antigen levels were measured at baseline and after 3 months of treatment by commercially available ELISA kits. Variations of individuals were assessed by Wilcoxon's test. Relationship between those markers and demographic characteristics were investigated. RESULTS: Three months of raloxifene treatment was associated with a significant decrease in the plasma TAFI antigen concentrations (16% change, P < 0.01), and a significant increase in tPA antigen concentrations (25% change, P < 0.05). A significant correlation was found between baseline TAFI antigen concentrations and the duration of amenorrhea (P < 0.05; r = 0.33). CONCLUSION: We suggest that the increased risk of venous thromboembolism due to raloxifene treatment may be related to increased tPA levels, but not TAFI levels.","[{'text': 'raloxifene', 'type': 'Chemical', 'start': 26, 'end': 36, 'mesh': 'D020849'}, {'text': 'raloxifene', 'type': 'Chemical', 'start': 332, 'end': 342, 'mesh': 'D020849'}, {'text': 'osteopenia', 'type': 'Disease', 'start': 430, 'end': 440, 'mesh': 'D001851'}, {'text': 'osteoporosis', 'type': 'Disease', 'start': 444, 'end': 456, 'mesh': 'D010024'}, {'text': 'raloxifene hydrochloride', 'type': 'Chemical', 'start': 548, 'end': 572, 'mesh': 'D020849'}, {'text': 'calcium', 'type': 'Chemical', 'start': 590, 'end': 597, 'mesh': 'D002118'}, {'text': 'calcium', 'type': 'Chemical', 'start': 658, 'end': 665, 'mesh': 'D002118'}, {'text': 'raloxifene', 'type': 'Chemical', 'start': 977, 'end': 987, 'mesh': 'D020849'}, {'text': 'amenorrhea', 'type': 'Disease', 'start': 1289, 'end': 1299, 'mesh': 'D000568'}, {'text': 'venous thromboembolism', 'type': 'Disease', 'start': 1372, 'end': 1394, 'mesh': 'D054556'}, {'text': 'raloxifene', 'type': 'Chemical', 'start': 1402, 'end': 1412, 'mesh': 'D020849'}]"
+155,16403073,Ketoconazole induced torsades de pointes without concomitant use of QT interval-prolonging drug.,"Ketoconazole is not known to be proarrhythmic without concomitant use of QT interval-prolonging drugs. We report a woman with coronary artery disease who developed a markedly prolonged QT interval and torsades de pointes (TdP) after taking ketoconazole for treatment of fungal infection. Her QT interval returned to normal upon withdrawal of ketoconazole. Genetic study did not find any mutation in her genes that encode cardiac IKr channel proteins. We postulate that by virtue of its direct blocking action on IKr, ketoconazole alone may prolong QT interval and induce TdP. This calls for attention when ketoconazole is administered to patients with risk factors for acquired long QT syndrome.","[{'text': 'Ketoconazole', 'type': 'Chemical', 'start': 0, 'end': 12, 'mesh': 'D007654'}, {'text': 'torsades de pointes', 'type': 'Disease', 'start': 21, 'end': 40, 'mesh': 'D016171'}, {'text': 'Ketoconazole', 'type': 'Chemical', 'start': 97, 'end': 109, 'mesh': 'D007654'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 223, 'end': 246, 'mesh': 'D003324'}, {'text': 'prolonged QT interval', 'type': 'Disease', 'start': 272, 'end': 293, 'mesh': 'D008133'}, {'text': 'torsades de pointes', 'type': 'Disease', 'start': 298, 'end': 317, 'mesh': 'D016171'}, {'text': 'TdP', 'type': 'Disease', 'start': 319, 'end': 322, 'mesh': 'D016171'}, {'text': 'ketoconazole', 'type': 'Chemical', 'start': 337, 'end': 349, 'mesh': 'D007654'}, {'text': 'fungal infection', 'type': 'Disease', 'start': 367, 'end': 383, 'mesh': 'D009181'}, {'text': 'ketoconazole', 'type': 'Chemical', 'start': 439, 'end': 451, 'mesh': 'D007654'}, {'text': 'ketoconazole', 'type': 'Chemical', 'start': 614, 'end': 626, 'mesh': 'D007654'}, {'text': 'TdP', 'type': 'Disease', 'start': 668, 'end': 671, 'mesh': 'D016171'}, {'text': 'ketoconazole', 'type': 'Chemical', 'start': 703, 'end': 715, 'mesh': 'D007654'}, {'text': 'long QT syndrome', 'type': 'Disease', 'start': 775, 'end': 791, 'mesh': 'D008133'}]"
+156,16755009,Pharmacological evidence for the potential of Daucus carota in the management of cognitive dysfunctions.,"The present study was aimed at investigating the effects of Daucus carota seeds on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. The ethanolic extract of Daucus carota seeds (DCE) was administered orally in three doses (100, 200, 400 mg/kg) for seven successive days to different groups of young and aged mice. Elevated plus maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam-, scopolamine- and ageing-induced amnesia served as the interoceptive behavioral models. DCE (200, 400 mg/kg, p.o.) showed significant improvement in memory scores of young and aged mice. The extent of memory improvement evoked by DCE was 23% at the dose of 200 mg/kg and 35% at the dose of 400 mg/kg in young mice using elevated plus maze. Similarly, significant improvements in memory scores were observed using passive avoidance apparatus and aged mice. Furthermore, DCE reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Daucus carota extract (200, 400 mg/kg, p.o.) reduced significantly the brain acetylcholinesterase activity and cholesterol levels in young and aged mice. The extent of inhibition of brain cholinesterase activity evoked by DCE at the dose of 400 mg/kg was 22% in young and 19% in aged mice. There was a remarkable reduction in total cholesterol level as well, to the extent of 23% in young and 21% in aged animals with this dose of DCE. Therefore, DCE may prove to be a useful remedy for the management of cognitive dysfunctions on account of its multifarious beneficial effects such as, memory improving property, cholesterol lowering property and anticholinesterase activity.","[{'text': 'cognitive dysfunctions', 'type': 'Disease', 'start': 81, 'end': 103, 'mesh': 'D003072'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 221, 'end': 232, 'mesh': 'D002784'}, {'text': 'extract of Daucus carota seeds', 'type': 'Chemical', 'start': 297, 'end': 327, 'mesh': 'D010936'}, {'text': 'DCE', 'type': 'Chemical', 'start': 329, 'end': 332, 'mesh': 'D010936'}, {'text': 'Diazepam', 'type': 'Chemical', 'start': 582, 'end': 590, 'mesh': 'D003975'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 593, 'end': 604, 'mesh': 'D012601'}, {'text': 'amnesia', 'type': 'Disease', 'start': 625, 'end': 632, 'mesh': 'D000647'}, {'text': 'DCE', 'type': 'Chemical', 'start': 680, 'end': 683, 'mesh': 'D010936'}, {'text': 'DCE', 'type': 'Chemical', 'start': 822, 'end': 825, 'mesh': 'D010936'}, {'text': 'DCE', 'type': 'Chemical', 'start': 1061, 'end': 1064, 'mesh': 'D010936'}, {'text': 'amnesia', 'type': 'Disease', 'start': 1078, 'end': 1085, 'mesh': 'D000647'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 1097, 'end': 1108, 'mesh': 'D012601'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 1131, 'end': 1139, 'mesh': 'D003975'}, {'text': 'Daucus carota extract', 'type': 'Chemical', 'start': 1157, 'end': 1178, 'mesh': 'D010936'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 1268, 'end': 1279, 'mesh': 'D002784'}, {'text': 'DCE', 'type': 'Chemical', 'start': 1379, 'end': 1382, 'mesh': 'D010936'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 1489, 'end': 1500, 'mesh': 'D002784'}, {'text': 'DCE', 'type': 'Chemical', 'start': 1588, 'end': 1591, 'mesh': 'D010936'}, {'text': 'DCE', 'type': 'Chemical', 'start': 1604, 'end': 1607, 'mesh': 'D010936'}, {'text': 'cognitive dysfunctions', 'type': 'Disease', 'start': 1662, 'end': 1684, 'mesh': 'D003072'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 1771, 'end': 1782, 'mesh': 'D002784'}]"
+157,16904497,Cauda equina syndrome after epidural steroid injection: a case report.,"OBJECTIVE: Conventional treatment methods of lumbusacral radiculopathy are physical therapy, epidural steroid injections, oral medications, and spinal manipulative therapy. Cauda equina syndrome is a rare complication of epidural anesthesia. The following case is a report of cauda equina syndrome possibly caused by epidural injection of triamcinolone and bupivacaine. CLINICAL FEATURES: A 50-year-old woman with low back and right leg pain was scheduled for epidural steroid injection. INTERVENTION AND OUTCOME: An 18-gauge Touhy needle was inserted until loss of resistance occurred at the L4-5 level. Spread of the contrast medium within the epidural space was determined by radiographic imaging. After verifying the epidural space, bupivacaine and triamcinolone diacetate were injected. After the injection, there was a reduction in radicular symptoms. Three hours later, she complained of perineal numbness and lower extremity weakness. The neurologic evaluation revealed loss of sensation in the saddle area and medial aspect of her right leg. There was a decrease in the perception of pinprick test. Deep-tendon reflexes were decreased especially in the right leg. She was unable to urinate. The patient's symptoms improved slightly over the next few hours. She had a gradual return of motor function and ability of feeling Foley catheter. All of the symptoms were completely resolved over the next 8 hours. CONCLUSION: Complications associated with epidural steroid injections are rare. Clinical examination and continued vigilance for neurologic deterioration after epidural steroid injections is important.","[{'text': 'Cauda equina syndrome', 'type': 'Disease', 'start': 0, 'end': 21, 'mesh': 'D011128'}, {'text': 'steroid', 'type': 'Chemical', 'start': 37, 'end': 44, 'mesh': 'D013256'}, {'text': 'radiculopathy', 'type': 'Disease', 'start': 128, 'end': 141, 'mesh': 'D011843'}, {'text': 'steroid', 'type': 'Chemical', 'start': 173, 'end': 180, 'mesh': 'D013256'}, {'text': 'Cauda equina syndrome', 'type': 'Disease', 'start': 244, 'end': 265, 'mesh': 'D011128'}, {'text': 'cauda equina syndrome', 'type': 'Disease', 'start': 347, 'end': 368, 'mesh': 'D011128'}, {'text': 'triamcinolone', 'type': 'Chemical', 'start': 410, 'end': 423, 'mesh': 'D014221'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 428, 'end': 439, 'mesh': 'D002045'}, {'text': 'steroid', 'type': 'Chemical', 'start': 540, 'end': 547, 'mesh': 'D013256'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 808, 'end': 819, 'mesh': 'D002045'}, {'text': 'triamcinolone diacetate', 'type': 'Chemical', 'start': 824, 'end': 847, 'mesh': 'C030262'}, {'text': 'numbness', 'type': 'Disease', 'start': 975, 'end': 983, 'mesh': 'D006987'}, {'text': 'lower extremity weakness', 'type': 'Disease', 'start': 988, 'end': 1012, 'mesh': 'D020335'}, {'text': 'loss of sensation', 'type': 'Disease', 'start': 1049, 'end': 1066, 'mesh': 'D006987'}, {'text': 'steroid', 'type': 'Chemical', 'start': 1538, 'end': 1545, 'mesh': 'D013256'}, {'text': 'neurologic deterioration', 'type': 'Disease', 'start': 1616, 'end': 1640, 'mesh': 'D009422'}, {'text': 'steroid', 'type': 'Chemical', 'start': 1656, 'end': 1663, 'mesh': 'D013256'}]"
+158,16938416,High-dose testosterone is associated with atherosclerosis in postmenopausal women.,"OBJECTIVES: To study the long-term effects of androgen treatment on atherosclerosis in postmenopausal women. METHODS: In a population-based study in 513 naturally postmenopausal women aged 54-67 years, we studied the association between self-reported intramuscularly administered high-dose estrogen-testosterone therapy (estradiol- and testosterone esters) and aortic atherosclerosis. Aortic atherosclerosis was diagnosed by radiographic detection of calcified deposits in the abdominal aorta, which have been shown to reflect intima atherosclerosis. Hormone therapy users were compared with never users. RESULTS: Intramuscular hormone therapy use for 1 year or longer was reported by 25 women. In almost half of these women severe atherosclerosis of the aorta was present (n=11), while in women without hormone use severe atherosclerosis of the aorta was present in less than 20% (OR 3.1; 95% CI, 1.1-8.5, adjusted for age, years since menopause, smoking, and body mass index). The association remained after additional adjustment for diabetes, cholesterol level, systolic blood pressure, or alcohol use. No association was found for hormone use less than 1 year. CONCLUSION: Our results suggest that high-dose testosterone therapy may adversely affect atherosclerosis in postmenopausal women and indicate that androgen replacement in these women may not be harmless.","[{'text': 'testosterone', 'type': 'Chemical', 'start': 10, 'end': 22, 'mesh': 'D013739'}, {'text': 'atherosclerosis', 'type': 'Disease', 'start': 42, 'end': 57, 'mesh': 'D050197'}, {'text': 'atherosclerosis', 'type': 'Disease', 'start': 151, 'end': 166, 'mesh': 'D050197'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 373, 'end': 381, 'mesh': 'D004967'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 382, 'end': 394, 'mesh': 'D013739'}, {'text': 'estradiol- and testosterone esters', 'type': 'Chemical', 'start': 404, 'end': 438, 'mesh': 'C032109'}, {'text': 'atherosclerosis', 'type': 'Disease', 'start': 451, 'end': 466, 'mesh': 'D050197'}, {'text': 'atherosclerosis', 'type': 'Disease', 'start': 475, 'end': 490, 'mesh': 'D050197'}, {'text': 'atherosclerosis', 'type': 'Disease', 'start': 617, 'end': 632, 'mesh': 'D050197'}, {'text': 'atherosclerosis', 'type': 'Disease', 'start': 815, 'end': 830, 'mesh': 'D050197'}, {'text': 'atherosclerosis', 'type': 'Disease', 'start': 906, 'end': 921, 'mesh': 'D050197'}, {'text': 'diabetes', 'type': 'Disease', 'start': 1119, 'end': 1127, 'mesh': 'D003920'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 1129, 'end': 1140, 'mesh': 'D002784'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 1176, 'end': 1183, 'mesh': 'D000431'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 1295, 'end': 1307, 'mesh': 'D013739'}, {'text': 'atherosclerosis', 'type': 'Disease', 'start': 1337, 'end': 1352, 'mesh': 'D050197'}]"
+159,17147461,Sirolimus-associated proteinuria and renal dysfunction.,"Sirolimus is a novel immunosuppressant with potent antiproliferative actions through its ability to inhibit the raptor-containing mammalian target of rapamycin protein kinase. Sirolimus represents a major therapeutic advance in the prevention of acute renal allograft rejection and chronic allograft nephropathy. Its role in the therapy of glomerulonephritis, autoimmunity, cystic renal diseases and renal cancer is under investigation. Because sirolimus does not share the vasomotor renal adverse effects exhibited by calcineurin inhibitors, it has been designated a 'non-nephrotoxic drug'. However, clinical reports suggest that, under some circumstances, sirolimus is associated with proteinuria and acute renal dysfunction. A common risk factor appears to be presence of pre-existing chronic renal damage. The mechanisms of sirolimus-associated proteinuria are multifactorial and may be due to an increase in glomerular capillary pressure following calcineurin inhibitor withdrawal. It has also been suggested that sirolimus directly causes increased glomerular permeability/injury, but evidence for this mechanism is currently inconclusive. The acute renal dysfunction associated with sirolimus (such as in delayed graft function) may be due to suppression of compensatory renal cell proliferation and survival/repair processes. Although these adverse effects occur in some patients, their occurrence could be minimised by knowledge of the molecular effects of sirolimus on the kidney, the use of sirolimus in appropriate patient populations, close monitoring of proteinuria and renal function, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers if proteinuria occurs and withdrawal if needed. Further long-term analysis of renal allograft studies using sirolimus as de novo immunosuppression along with clinical and laboratory studies will refine these issues in the future.","[{'text': 'Sirolimus', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D020123'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 21, 'end': 32, 'mesh': 'D011507'}, {'text': 'renal dysfunction', 'type': 'Disease', 'start': 37, 'end': 54, 'mesh': 'D007674'}, {'text': 'Sirolimus', 'type': 'Chemical', 'start': 56, 'end': 65, 'mesh': 'D020123'}, {'text': 'rapamycin', 'type': 'Chemical', 'start': 206, 'end': 215, 'mesh': 'D020123'}, {'text': 'Sirolimus', 'type': 'Chemical', 'start': 232, 'end': 241, 'mesh': 'D020123'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 356, 'end': 367, 'mesh': 'D007674'}, {'text': 'glomerulonephritis', 'type': 'Disease', 'start': 396, 'end': 414, 'mesh': 'D005921'}, {'text': 'autoimmunity', 'type': 'Disease', 'start': 416, 'end': 428, 'mesh': 'D001327'}, {'text': 'cystic renal diseases', 'type': 'Disease', 'start': 430, 'end': 451, 'mesh': 'D052177'}, {'text': 'renal cancer', 'type': 'Disease', 'start': 456, 'end': 468, 'mesh': 'D007680'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 501, 'end': 510, 'mesh': 'D020123'}, {'text': 'nephrotoxic', 'type': 'Disease', 'start': 629, 'end': 640, 'mesh': 'D007674'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 714, 'end': 723, 'mesh': 'D020123'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 743, 'end': 754, 'mesh': 'D011507'}, {'text': 'acute renal dysfunction', 'type': 'Disease', 'start': 759, 'end': 782, 'mesh': 'D058186'}, {'text': 'chronic renal damage', 'type': 'Disease', 'start': 844, 'end': 864, 'mesh': 'D051436'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 884, 'end': 893, 'mesh': 'D020123'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 905, 'end': 916, 'mesh': 'D011507'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 1075, 'end': 1084, 'mesh': 'D020123'}, {'text': 'acute renal dysfunction', 'type': 'Disease', 'start': 1206, 'end': 1229, 'mesh': 'D058186'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 1246, 'end': 1255, 'mesh': 'D020123'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 1522, 'end': 1531, 'mesh': 'D020123'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 1558, 'end': 1567, 'mesh': 'D020123'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1624, 'end': 1635, 'mesh': 'D011507'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 1663, 'end': 1674, 'mesh': 'D000809'}, {'text': 'angiotensin II', 'type': 'Chemical', 'start': 1707, 'end': 1721, 'mesh': 'D000804'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1743, 'end': 1754, 'mesh': 'D011507'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 1848, 'end': 1857, 'mesh': 'D020123'}]"
+160,17241784,Progressive myopathy with up-regulation of MHC-I associated with statin therapy.,"Statins can cause a necrotizing myopathy and hyperCKaemia which is reversible on cessation of the drug. What is less well known is a phenomenon whereby statins may induce a myopathy, which persists or may progress after stopping the drug. We investigated the muscle pathology in 8 such cases. All had myofibre necrosis but only 3 had an inflammatory infiltrate. In all cases there was diffuse or multifocal up-regulation of MHC-I expression even in non-necrotic fibres. Progressive improvement occurred in 7 cases after commencement of prednisolone and methotrexate, and in one case spontaneously. These observations suggest that statins may initiate an immune-mediated myopathy that persists after withdrawal of the drug and responds to immunosuppressive therapy. The mechanism of this myopathy is uncertain but may involve the induction by statins of an endoplasmic reticulum stress response with associated up-regulation of MHC-I expression and antigen presentation by muscle fibres.","[{'text': 'myopathy', 'type': 'Disease', 'start': 12, 'end': 20, 'mesh': 'D009135'}, {'text': 'statin', 'type': 'Chemical', 'start': 65, 'end': 71, 'mesh': 'D019821'}, {'text': 'Statins', 'type': 'Chemical', 'start': 81, 'end': 88, 'mesh': 'D019821'}, {'text': 'myopathy', 'type': 'Disease', 'start': 113, 'end': 121, 'mesh': 'D009135'}, {'text': 'hyperCKaemia', 'type': 'Disease', 'start': 126, 'end': 138, 'mesh': '-1'}, {'text': 'statins', 'type': 'Chemical', 'start': 233, 'end': 240, 'mesh': 'D019821'}, {'text': 'myopathy', 'type': 'Disease', 'start': 254, 'end': 262, 'mesh': 'D009135'}, {'text': 'necrosis', 'type': 'Disease', 'start': 391, 'end': 399, 'mesh': 'D009336'}, {'text': 'necrotic', 'type': 'Disease', 'start': 534, 'end': 542, 'mesh': 'D009336'}, {'text': 'prednisolone', 'type': 'Chemical', 'start': 617, 'end': 629, 'mesh': 'D011239'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 634, 'end': 646, 'mesh': 'D008727'}, {'text': 'statins', 'type': 'Chemical', 'start': 711, 'end': 718, 'mesh': 'D019821'}, {'text': 'myopathy', 'type': 'Disease', 'start': 751, 'end': 759, 'mesh': 'D009135'}, {'text': 'myopathy', 'type': 'Disease', 'start': 868, 'end': 876, 'mesh': 'D009135'}, {'text': 'statins', 'type': 'Chemical', 'start': 923, 'end': 930, 'mesh': 'D019821'}]"
+161,17261653,Direct inhibition of cardiac hyperpolarization-activated cyclic nucleotide-gated pacemaker channels by clonidine.,"BACKGROUND: Inhibition of cardiac sympathetic tone represents an important strategy for treatment of cardiovascular disease, including arrhythmia, coronary heart disease, and chronic heart failure. Activation of presynaptic alpha2-adrenoceptors is the most widely accepted mechanism of action of the antisympathetic drug clonidine; however, other target proteins have been postulated to contribute to the in vivo actions of clonidine. METHODS AND RESULTS: To test whether clonidine elicits pharmacological effects independent of alpha2-adrenoceptors, we have generated mice with a targeted deletion of all 3 alpha2-adrenoceptor subtypes (alpha2ABC-/-). Alpha2ABC-/- mice were completely unresponsive to the analgesic and hypnotic effects of clonidine; however, clonidine significantly lowered heart rate in alpha2ABC-/- mice by up to 150 bpm. Clonidine-induced bradycardia in conscious alpha2ABC-/- mice was 32.3% (10 microg/kg) and 26.6% (100 microg/kg) of the effect in wild-type mice. A similar bradycardic effect of clonidine was observed in isolated spontaneously beating right atria from alpha2ABC-knockout and wild-type mice. Clonidine inhibited the native pacemaker current (I(f)) in isolated sinoatrial node pacemaker cells and the I(f)-generating hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 and HCN4 channels in transfected HEK293 cells. As a consequence of blocking I(f), clonidine reduced the slope of the diastolic depolarization and the frequency of pacemaker potentials in sinoatrial node cells from wild-type and alpha2ABC-knockout mice. CONCLUSIONS: Direct inhibition of cardiac HCN pacemaker channels contributes to the bradycardic effects of clonidine gene-targeted mice in vivo, and thus, clonidine-like drugs represent novel structures for future HCN channel inhibitors.","[{'text': 'cyclic nucleotide', 'type': 'Chemical', 'start': 57, 'end': 74, 'mesh': 'D009712'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 103, 'end': 112, 'mesh': 'D003000'}, {'text': 'cardiovascular disease', 'type': 'Disease', 'start': 215, 'end': 237, 'mesh': 'D002318'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 249, 'end': 259, 'mesh': 'D001145'}, {'text': 'coronary heart disease', 'type': 'Disease', 'start': 261, 'end': 283, 'mesh': 'D003327'}, {'text': 'heart failure', 'type': 'Disease', 'start': 297, 'end': 310, 'mesh': 'D006333'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 435, 'end': 444, 'mesh': 'D003000'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 538, 'end': 547, 'mesh': 'D003000'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 586, 'end': 595, 'mesh': 'D003000'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 855, 'end': 864, 'mesh': 'D003000'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 875, 'end': 884, 'mesh': 'D003000'}, {'text': 'Clonidine', 'type': 'Chemical', 'start': 957, 'end': 966, 'mesh': 'D003000'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 975, 'end': 986, 'mesh': 'D001919'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 1134, 'end': 1143, 'mesh': 'D003000'}, {'text': 'Clonidine', 'type': 'Chemical', 'start': 1247, 'end': 1256, 'mesh': 'D003000'}, {'text': 'cyclic nucleotide', 'type': 'Chemical', 'start': 1399, 'end': 1416, 'mesh': 'D009712'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 1513, 'end': 1522, 'mesh': 'D003000'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 1791, 'end': 1800, 'mesh': 'D003000'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 1839, 'end': 1848, 'mesh': 'D003000'}]"
+162,17343925,Influence of smoking on developing cochlea. Does smoking during pregnancy affect the amplitudes of transient evoked otoacoustic emissions in newborns?,"OBJECTIVE: Maternal tobacco smoking has negative effects on fetal growth. The influence of smoking during pregnancy on the developing cochlea has not been estimated, although smoking has been positively associated with hearing loss in adults. The objective of this study was to determine the effects of maternal smoking on transient evoked otoacoustic emissions (TEOAEs) of healthy neonates. METHODS: This study was undertaken as part of neonatal screening for hearing impairment and involved both ears of 200 newborns. Newborns whose mothers reported smoking during pregnancy (n=200 ears) were compared to a control group of newborns (n=200 ears), whose mothers were non-smokers. Exposure to tobacco was characterized as low (<5 cigarettes per day, n=88 ears), moderate (5< or =cigarettes per day<10, n=76) or high (> or =10 cigarettes per day, n=36). RESULTS: In exposed neonates, TEOAEs mean response (across frequency) and mean amplitude at 4000Hz was significantly lower than in non-exposed neonates. Comparisons between exposed newborns' subgroups revealed no significant differences. However, by comparing each subgroup to control group, we found statistically significant decreases of TEOAEs amplitudes at 4000Hz for all three groups. Mean TEOAEs responses of highly exposed newborns were also significantly lower in comparison to our control group. CONCLUSION: In utero, exposure to tobacco smoking seems to have a small impact on outer hair cells. These effects seem to be equally true for all exposed newborns, regardless of the degree of exposure. Further studies are needed in order to establish a potential negative effect of maternal smoking on the neonate's hearing acuity.","[{'text': 'smoking', 'type': 'Chemical', 'start': 13, 'end': 20, 'mesh': 'D012906'}, {'text': 'smoking', 'type': 'Chemical', 'start': 49, 'end': 56, 'mesh': 'D012906'}, {'text': 'smoking', 'type': 'Chemical', 'start': 179, 'end': 186, 'mesh': 'D012906'}, {'text': 'smoking', 'type': 'Chemical', 'start': 242, 'end': 249, 'mesh': 'D012906'}, {'text': 'smoking', 'type': 'Chemical', 'start': 326, 'end': 333, 'mesh': 'D012906'}, {'text': 'hearing loss', 'type': 'Disease', 'start': 370, 'end': 382, 'mesh': 'D034381'}, {'text': 'smoking', 'type': 'Chemical', 'start': 463, 'end': 470, 'mesh': 'D012906'}, {'text': 'hearing impairment', 'type': 'Disease', 'start': 612, 'end': 630, 'mesh': 'D034381'}, {'text': 'smoking', 'type': 'Chemical', 'start': 703, 'end': 710, 'mesh': 'D012906'}, {'text': 'decreases of TEOAEs amplitudes', 'type': 'Disease', 'start': 1331, 'end': 1361, 'mesh': '-1'}, {'text': 'smoking', 'type': 'Chemical', 'start': 1551, 'end': 1558, 'mesh': 'D012906'}, {'text': 'smoking', 'type': 'Chemical', 'start': 1800, 'end': 1807, 'mesh': 'D012906'}]"
+163,17400887,Neuroinflammation and behavioral abnormalities after neonatal terbutaline treatment in rats: implications for autism.,"Autism is a neurodevelopmental disorder presenting before 3 years of age with deficits in communication and social skills and repetitive behaviors. In addition to genetic influences, recent studies suggest that prenatal drug or chemical exposures are risk factors for autism. Terbutaline, a beta2-adrenoceptor agonist used to arrest preterm labor, has been associated with increased concordance for autism in dizygotic twins. We studied the effects of terbutaline on microglial activation in different brain regions and behavioral outcomes in developing rats. Newborn rats were given terbutaline (10 mg/kg) daily on postnatal days (PN) 2 to 5 or PN 11 to 14 and examined 24 h after the last dose and at PN 30. Immunohistochemical studies showed that administration of terbutaline on PN 2 to 5 produced a robust increase in microglial activation on PN 30 in the cerebral cortex, as well as in cerebellar and cerebrocortical white matter. None of these effects occurred in animals given terbutaline on PN 11 to 14. In behavioral tests, animals treated with terbutaline on PN 2 to 5 showed consistent patterns of hyper-reactivity to novelty and aversive stimuli when assessed in a novel open field, as well as in the acoustic startle response test. Our findings indicate that beta2-adrenoceptor overstimulation during an early critical period results in microglial activation associated with innate neuroinflammatory pathways and behavioral abnormalities, similar to those described in autism. This study provides a useful animal model for understanding the neuropathological processes underlying autism spectrum disorders.","[{'text': 'Neuroinflammation', 'type': 'Disease', 'start': 0, 'end': 17, 'mesh': 'D020078'}, {'text': 'behavioral abnormalities', 'type': 'Disease', 'start': 22, 'end': 46, 'mesh': 'D001523'}, {'text': 'terbutaline', 'type': 'Chemical', 'start': 62, 'end': 73, 'mesh': 'D013726'}, {'text': 'autism', 'type': 'Disease', 'start': 110, 'end': 116, 'mesh': 'D001321'}, {'text': 'Autism', 'type': 'Disease', 'start': 118, 'end': 124, 'mesh': 'D001321'}, {'text': 'neurodevelopmental disorder', 'type': 'Disease', 'start': 130, 'end': 157, 'mesh': 'D002658'}, {'text': 'deficits in communication and social skills', 'type': 'Disease', 'start': 196, 'end': 239, 'mesh': 'D003147'}, {'text': 'repetitive behaviors', 'type': 'Disease', 'start': 244, 'end': 264, 'mesh': 'D001523'}, {'text': 'autism', 'type': 'Disease', 'start': 386, 'end': 392, 'mesh': 'D001321'}, {'text': 'Terbutaline', 'type': 'Chemical', 'start': 394, 'end': 405, 'mesh': 'D013726'}, {'text': 'preterm labor', 'type': 'Disease', 'start': 451, 'end': 464, 'mesh': 'D007752'}, {'text': 'autism', 'type': 'Disease', 'start': 517, 'end': 523, 'mesh': 'D001321'}, {'text': 'terbutaline', 'type': 'Chemical', 'start': 570, 'end': 581, 'mesh': 'D013726'}, {'text': 'terbutaline', 'type': 'Chemical', 'start': 702, 'end': 713, 'mesh': 'D013726'}, {'text': 'terbutaline', 'type': 'Chemical', 'start': 886, 'end': 897, 'mesh': 'D013726'}, {'text': 'terbutaline', 'type': 'Chemical', 'start': 1103, 'end': 1114, 'mesh': 'D013726'}, {'text': 'terbutaline', 'type': 'Chemical', 'start': 1173, 'end': 1184, 'mesh': 'D013726'}, {'text': 'behavioral abnormalities', 'type': 'Disease', 'start': 1545, 'end': 1569, 'mesh': 'D001523'}, {'text': 'autism', 'type': 'Disease', 'start': 1601, 'end': 1607, 'mesh': 'D001321'}, {'text': 'autism spectrum disorders', 'type': 'Disease', 'start': 1712, 'end': 1737, 'mesh': 'D002659'}]"
+164,17612891,Acute myocarditis associated with clozapine.,"OBJECTIVE: A case of acute myocarditis associated with the commencement of clozapine is described, highlighting the onset, course and possible contributing factors. There is an urgent need to raise awareness about this potentially fatal complication of clozapine use. RESULTS: A 20-year-old male with schizophrenia developed a sudden onset of myocarditis after commencement of clozapine. The patient recovered with intensive medical support. The symptoms occurred around 2 weeks after starting clozapine in an inpatient setting. Possible contributing factors may have been concomitant antidepressant use and unaccustomed physical activity. CONCLUSIONS: Myocarditis is an increasingly recognized complication associated with the use of clozapine. It can be fatal if not recognized and treated early. Considering that clozapine remains the gold standard in treatment of resistant psychosis, there is an urgent need to raise awareness among medical and paramedical staff involved in the care of these patients. There are also implications for recommendations and regulations regarding the use of clozapine.","[{'text': 'myocarditis', 'type': 'Disease', 'start': 6, 'end': 17, 'mesh': 'D009205'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 34, 'end': 43, 'mesh': 'D003024'}, {'text': 'myocarditis', 'type': 'Disease', 'start': 72, 'end': 83, 'mesh': 'D009205'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 120, 'end': 129, 'mesh': 'D003024'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 298, 'end': 307, 'mesh': 'D003024'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 346, 'end': 359, 'mesh': 'D012559'}, {'text': 'myocarditis', 'type': 'Disease', 'start': 388, 'end': 399, 'mesh': 'D009205'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 422, 'end': 431, 'mesh': 'D003024'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 539, 'end': 548, 'mesh': 'D003024'}, {'text': 'antidepressant', 'type': 'Chemical', 'start': 630, 'end': 644, 'mesh': 'D000928'}, {'text': 'Myocarditis', 'type': 'Disease', 'start': 698, 'end': 709, 'mesh': 'D009205'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 780, 'end': 789, 'mesh': 'D003024'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 861, 'end': 870, 'mesh': 'D003024'}, {'text': 'psychosis', 'type': 'Disease', 'start': 923, 'end': 932, 'mesh': 'D011618'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 1138, 'end': 1147, 'mesh': 'D003024'}]"
+165,18081909,Encephalopathy induced by levetiracetam added to valproate.,"BACKGROUND: We report on the manifestation of a levetiracetam (LEV)-induced encephalopathy. FINDINGS: A 28-year-old man suffering from idiopathic epilepsy with generalized seizures was treated with LEV (3000 mg) added to valproate (VPA) (2000 mg). Frequency of generalized tonic-clonic seizures increased from one per 6 months to two per month. Neuropsychological testing showed impaired word fluency, psychomotor speed and working memory. The interictal electroencephalogram (EEG) showed a generalized slowing to 5 per second theta rhythms with bilateral generalized high-amplitude discharges. OUTCOME: Following discontinuation of LEV, EEG and neuropsychological findings improved and seizure frequency decreased.","[{'text': 'Encephalopathy', 'type': 'Disease', 'start': 0, 'end': 14, 'mesh': 'D001927'}, {'text': 'levetiracetam', 'type': 'Chemical', 'start': 26, 'end': 39, 'mesh': 'C026098'}, {'text': 'valproate', 'type': 'Chemical', 'start': 49, 'end': 58, 'mesh': 'D014635'}, {'text': 'levetiracetam', 'type': 'Chemical', 'start': 108, 'end': 121, 'mesh': 'C026098'}, {'text': 'LEV', 'type': 'Chemical', 'start': 123, 'end': 126, 'mesh': 'C026098'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 136, 'end': 150, 'mesh': 'D001927'}, {'text': 'idiopathic epilepsy', 'type': 'Disease', 'start': 195, 'end': 214, 'mesh': 'C562694'}, {'text': 'seizures', 'type': 'Disease', 'start': 232, 'end': 240, 'mesh': 'D012640'}, {'text': 'LEV', 'type': 'Chemical', 'start': 258, 'end': 261, 'mesh': 'C026098'}, {'text': 'valproate', 'type': 'Chemical', 'start': 281, 'end': 290, 'mesh': 'D014635'}, {'text': 'VPA', 'type': 'Chemical', 'start': 292, 'end': 295, 'mesh': 'D014635'}, {'text': 'tonic-clonic seizures', 'type': 'Disease', 'start': 333, 'end': 354, 'mesh': 'D004830'}, {'text': 'impaired word fluency, psychomotor speed and working memory', 'type': 'Disease', 'start': 439, 'end': 498, 'mesh': 'D008569'}, {'text': 'LEV', 'type': 'Chemical', 'start': 693, 'end': 696, 'mesh': 'C026098'}, {'text': 'seizure', 'type': 'Disease', 'start': 747, 'end': 754, 'mesh': 'D012640'}]"
+166,18083142,Norepinephrine signaling through beta-adrenergic receptors is critical for expression of cocaine-induced anxiety.,"BACKGROUND: Cocaine is a widely abused psychostimulant that has both rewarding and aversive properties. While the mechanisms underlying cocaine's rewarding effects have been studied extensively, less attention has been paid to the unpleasant behavioral states induced by cocaine, such as anxiety. METHODS: In this study, we evaluated the performance of dopamine beta-hydroxylase knockout (Dbh -/-) mice, which lack norepinephrine (NE), in the elevated plus maze (EPM) to examine the contribution of noradrenergic signaling to cocaine-induced anxiety. RESULTS: We found that cocaine dose-dependently increased anxiety-like behavior in control (Dbh +/-) mice, as measured by a decrease in open arm exploration. The Dbh -/- mice had normal baseline performance in the EPM but were completely resistant to the anxiogenic effects of cocaine. Cocaine-induced anxiety was also attenuated in Dbh +/- mice following administration of disulfiram, a dopamine beta-hydroxylase (DBH) inhibitor. In experiments using specific adrenergic antagonists, we found that pretreatment with the beta-adrenergic receptor antagonist propranolol blocked cocaine-induced anxiety-like behavior in Dbh +/- and wild-type C57BL6/J mice, while the alpha(1) antagonist prazosin and the alpha(2) antagonist yohimbine had no effect. CONCLUSIONS: These results indicate that noradrenergic signaling via beta-adrenergic receptors is required for cocaine-induced anxiety in mice.","[{'text': 'Norepinephrine', 'type': 'Chemical', 'start': 0, 'end': 14, 'mesh': 'D009638'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 89, 'end': 96, 'mesh': 'D003042'}, {'text': 'anxiety', 'type': 'Disease', 'start': 105, 'end': 112, 'mesh': 'D001008'}, {'text': 'Cocaine', 'type': 'Chemical', 'start': 126, 'end': 133, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 250, 'end': 257, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 385, 'end': 392, 'mesh': 'D003042'}, {'text': 'anxiety', 'type': 'Disease', 'start': 402, 'end': 409, 'mesh': 'D001008'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 467, 'end': 475, 'mesh': 'D004298'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 529, 'end': 543, 'mesh': 'D009638'}, {'text': 'NE', 'type': 'Chemical', 'start': 545, 'end': 547, 'mesh': 'D009638'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 640, 'end': 647, 'mesh': 'D003042'}, {'text': 'anxiety', 'type': 'Disease', 'start': 656, 'end': 663, 'mesh': 'D001008'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 688, 'end': 695, 'mesh': 'D003042'}, {'text': 'anxiety', 'type': 'Disease', 'start': 723, 'end': 730, 'mesh': 'D001008'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 942, 'end': 949, 'mesh': 'D003042'}, {'text': 'Cocaine', 'type': 'Chemical', 'start': 951, 'end': 958, 'mesh': 'D003042'}, {'text': 'anxiety', 'type': 'Disease', 'start': 967, 'end': 974, 'mesh': 'D001008'}, {'text': 'disulfiram', 'type': 'Chemical', 'start': 1039, 'end': 1049, 'mesh': 'D004221'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1053, 'end': 1061, 'mesh': 'D004298'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 1222, 'end': 1233, 'mesh': 'D011433'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1242, 'end': 1249, 'mesh': 'D003042'}, {'text': 'anxiety', 'type': 'Disease', 'start': 1258, 'end': 1265, 'mesh': 'D001008'}, {'text': 'prazosin', 'type': 'Chemical', 'start': 1350, 'end': 1358, 'mesh': 'D011224'}, {'text': 'yohimbine', 'type': 'Chemical', 'start': 1387, 'end': 1396, 'mesh': 'D015016'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1523, 'end': 1530, 'mesh': 'D003042'}, {'text': 'anxiety', 'type': 'Disease', 'start': 1539, 'end': 1546, 'mesh': 'D001008'}]"
+167,18182964,Clonidine for attention-deficit/hyperactivity disorder: II. ECG changes and adverse events analysis.,"OBJECTIVE: To examine the safety and tolerability of clonidine used alone or with methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: In a 16-week multicenter, double-blind trial, 122 children with ADHD were randomly assigned to clonidine (n = 31), methylphenidate (n = 29), clonidine and methylphenidate (n = 32), or placebo (n = 30). Doses were flexibly titrated up to 0.6 mg/day for clonidine and 60 mg/day for methylphenidate (both with divided dosing). Groups were compared regarding adverse events and changes from baseline to week 16 in electrocardiograms and vital signs. RESULTS: There were more incidents of bradycardia in subjects treated with clonidine compared with those not treated with clonidine (17.5% versus 3.4%; p =.02), but no other significant group differences regarding electrocardiogram and other cardiovascular outcomes. There were no suggestions of interactions between clonidine and methylphenidate regarding cardiovascular outcomes. Moderate or severe adverse events were more common in subjects on clonidine (79.4% versus 49.2%; p =.0006) but not associated with higher rates of early study withdrawal. Drowsiness was common on clonidine, but generally resolved by 6 to 8 weeks. CONCLUSIONS: Clonidine, used alone or with methylphenidate, appears safe and well tolerated in childhood ADHD. Physicians prescribing clonidine should monitor for bradycardia and advise patients about the high likelihood of initial drowsiness.","[{'text': 'Clonidine', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D003000'}, {'text': 'attention-deficit/hyperactivity disorder', 'type': 'Disease', 'start': 14, 'end': 54, 'mesh': 'D001289'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 154, 'end': 163, 'mesh': 'D003000'}, {'text': 'methylphenidate', 'type': 'Chemical', 'start': 183, 'end': 198, 'mesh': 'D008774'}, {'text': 'attention-deficit/hyperactivity disorder', 'type': 'Disease', 'start': 216, 'end': 256, 'mesh': 'D001289'}, {'text': 'ADHD', 'type': 'Disease', 'start': 258, 'end': 262, 'mesh': 'D001289'}, {'text': 'ADHD', 'type': 'Disease', 'start': 337, 'end': 341, 'mesh': 'D001289'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 368, 'end': 377, 'mesh': 'D003000'}, {'text': 'methylphenidate', 'type': 'Chemical', 'start': 388, 'end': 403, 'mesh': 'D008774'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 414, 'end': 423, 'mesh': 'D003000'}, {'text': 'methylphenidate', 'type': 'Chemical', 'start': 428, 'end': 443, 'mesh': 'D008774'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 525, 'end': 534, 'mesh': 'D003000'}, {'text': 'methylphenidate', 'type': 'Chemical', 'start': 553, 'end': 568, 'mesh': 'D008774'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 757, 'end': 768, 'mesh': 'D001919'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 794, 'end': 803, 'mesh': 'D003000'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 841, 'end': 850, 'mesh': 'D003000'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 1036, 'end': 1045, 'mesh': 'D003000'}, {'text': 'methylphenidate', 'type': 'Chemical', 'start': 1050, 'end': 1065, 'mesh': 'D008774'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 1167, 'end': 1176, 'mesh': 'D003000'}, {'text': 'Drowsiness', 'type': 'Disease', 'start': 1272, 'end': 1282, 'mesh': 'D006970'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 1297, 'end': 1306, 'mesh': 'D003000'}, {'text': 'Clonidine', 'type': 'Chemical', 'start': 1361, 'end': 1370, 'mesh': 'D003000'}, {'text': 'methylphenidate', 'type': 'Chemical', 'start': 1391, 'end': 1406, 'mesh': 'D008774'}, {'text': 'ADHD', 'type': 'Disease', 'start': 1453, 'end': 1457, 'mesh': 'D001289'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 1482, 'end': 1491, 'mesh': 'D003000'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 1511, 'end': 1522, 'mesh': 'D001919'}, {'text': 'drowsiness', 'type': 'Disease', 'start': 1580, 'end': 1590, 'mesh': 'D006970'}]"
+168,18217897,Thalidomide has limited single-agent activity in relapsed or refractory indolent non-Hodgkin lymphomas: a phase II trial of the Cancer and Leukemia Group B.,"Thalidomide is an immunomodulatory agent with demonstrated activity in multiple myeloma, mantle cell lymphoma and lymphoplasmacytic lymphoma. Its activity is believed to be due modulation of the tumour milieu, including downregulation of angiogenesis and inflammatory cytokines. Between July 2001 and April 2004, 24 patients with relapsed/refractory indolent lymphomas received thalidomide 200 mg daily with escalation by 100 mg daily every 1-2 weeks as tolerated, up to a maximum of 800 mg daily. Patients had received a median of 2 (range, 1-4) prior regimens. Of 24 evaluable patients, two achieved a complete remission and one achieved a partial remission for an overall response rate of 12.5% (95% confidence interval: 2.6-32.4%). Eleven patients progressed during therapy. Grade 3-4 adverse effects included myelosuppression, fatigue, somnolence/depressed mood, neuropathy and dyspnea. Of concern was the occurrence of four thromboembolic events. Our results failed to demonstrate an important response rate to single agent thalidomide in indolent lymphomas and contrast with the higher activity level reported with the second generation immunomodulatory agent, lenalidomide.","[{'text': 'Thalidomide', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D013792'}, {'text': 'non-Hodgkin lymphomas', 'type': 'Disease', 'start': 81, 'end': 102, 'mesh': 'D008228'}, {'text': 'Cancer', 'type': 'Disease', 'start': 128, 'end': 134, 'mesh': 'D009369'}, {'text': 'Leukemia', 'type': 'Disease', 'start': 139, 'end': 147, 'mesh': 'D007938'}, {'text': 'Thalidomide', 'type': 'Chemical', 'start': 157, 'end': 168, 'mesh': 'D013792'}, {'text': 'multiple myeloma', 'type': 'Disease', 'start': 228, 'end': 244, 'mesh': 'D009101'}, {'text': 'mantle cell lymphoma', 'type': 'Disease', 'start': 246, 'end': 266, 'mesh': 'D020522'}, {'text': 'lymphoplasmacytic lymphoma', 'type': 'Disease', 'start': 271, 'end': 297, 'mesh': 'D008223'}, {'text': 'tumour', 'type': 'Disease', 'start': 352, 'end': 358, 'mesh': 'D009369'}, {'text': 'lymphomas', 'type': 'Disease', 'start': 516, 'end': 525, 'mesh': 'D008223'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 535, 'end': 546, 'mesh': 'D013792'}, {'text': 'myelosuppression', 'type': 'Disease', 'start': 971, 'end': 987, 'mesh': 'D001855'}, {'text': 'fatigue', 'type': 'Disease', 'start': 989, 'end': 996, 'mesh': 'D005221'}, {'text': 'somnolence', 'type': 'Disease', 'start': 998, 'end': 1008, 'mesh': 'D006970'}, {'text': 'depressed mood', 'type': 'Disease', 'start': 1009, 'end': 1023, 'mesh': 'D003866'}, {'text': 'neuropathy', 'type': 'Disease', 'start': 1025, 'end': 1035, 'mesh': 'D009422'}, {'text': 'dyspnea', 'type': 'Disease', 'start': 1040, 'end': 1047, 'mesh': 'D004417'}, {'text': 'thromboembolic', 'type': 'Disease', 'start': 1087, 'end': 1101, 'mesh': 'D013923'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 1187, 'end': 1198, 'mesh': 'D013792'}, {'text': 'lymphomas', 'type': 'Disease', 'start': 1211, 'end': 1220, 'mesh': 'D008223'}, {'text': 'lenalidomide', 'type': 'Chemical', 'start': 1325, 'end': 1337, 'mesh': 'C467567'}]"
+169,18996674,Intracavernous epinephrine: a minimally invasive treatment for priapism in the emergency department.,"Priapism is the prolonged erection of the penis in the absence of sexual arousal. A 45-year-old man, an admitted frequent cocaine user, presented to the Emergency Department (ED) on two separate occasions with a history of priapism after cocaine use. The management options in the ED, as exemplified by four individual case reports, in particular the use of a minimally invasive method of intracorporal epinephrine instillation, are discussed.","[{'text': 'epinephrine', 'type': 'Chemical', 'start': 15, 'end': 26, 'mesh': 'D004837'}, {'text': 'priapism', 'type': 'Disease', 'start': 63, 'end': 71, 'mesh': 'D011317'}, {'text': 'Priapism', 'type': 'Disease', 'start': 101, 'end': 109, 'mesh': 'D011317'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 223, 'end': 230, 'mesh': 'D003042'}, {'text': 'priapism', 'type': 'Disease', 'start': 324, 'end': 332, 'mesh': 'D011317'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 339, 'end': 346, 'mesh': 'D003042'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 504, 'end': 515, 'mesh': 'D004837'}]"
+170,19058010,Effect of green tea and vitamin E combination in isoproterenol induced myocardial infarction in rats.,"The present study was aimed to investigate the combined effects of green tea and vitamin E on heart weight, body weight, serum marker enzymes, lipid peroxidation, endogenous antioxidants and membrane bound ATPases in isoproterenol (ISO)-induced myocardial infarction in rats. Adult male albino rats, treated with ISO (200 mg/kg, s.c.) for 2 days at an interval of 24 h caused a significant (P<0.05) elevation of heart weight, serum marker enzymes, lipid peroxidation and Ca+2 ATPase level whereas there was a significant (P<0.05) decrease in body weight, endogenous antioxidants, Na+/ K+ ATPase and Mg+2 ATPase levels. Administration of green tea (100 mg/kg/day, p.o.) and vitamin E (100 mg/kg/day, p.o.) together for 30 consecutive days and challenged with ISO on the day 29th and 30th, showed a significant (P<0.05) decrease in heart weight, serum marker enzymes, lipid peroxidation, Ca+2 ATPase and a significant increase in the body weight, endogenous antioxidants, Na+/K+ ATPase and Mg+2 ATPase when compared with ISO treated group and green tea or vitamin E alone treated groups. These findings indicate the synergistic protective effect of green tea and vitamin E during ISO induced myocardial infarction in rats.","[{'text': 'green tea', 'type': 'Chemical', 'start': 10, 'end': 19, 'mesh': 'D010936'}, {'text': 'vitamin E', 'type': 'Chemical', 'start': 24, 'end': 33, 'mesh': 'D014810'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 49, 'end': 62, 'mesh': 'D007545'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 71, 'end': 92, 'mesh': 'D009203'}, {'text': 'green tea', 'type': 'Chemical', 'start': 169, 'end': 178, 'mesh': 'D010936'}, {'text': 'vitamin E', 'type': 'Chemical', 'start': 183, 'end': 192, 'mesh': 'D014810'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 319, 'end': 332, 'mesh': 'D007545'}, {'text': 'ISO', 'type': 'Chemical', 'start': 334, 'end': 337, 'mesh': 'D007545'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 347, 'end': 368, 'mesh': 'D009203'}, {'text': 'ISO', 'type': 'Chemical', 'start': 415, 'end': 418, 'mesh': 'D007545'}, {'text': 'Ca', 'type': 'Chemical', 'start': 573, 'end': 575, 'mesh': 'D002118'}, {'text': 'Na', 'type': 'Chemical', 'start': 682, 'end': 684, 'mesh': 'D012964'}, {'text': 'K', 'type': 'Chemical', 'start': 687, 'end': 688, 'mesh': 'D011188'}, {'text': 'Mg', 'type': 'Chemical', 'start': 701, 'end': 703, 'mesh': 'D008274'}, {'text': 'green tea', 'type': 'Chemical', 'start': 739, 'end': 748, 'mesh': 'D010936'}, {'text': 'vitamin E', 'type': 'Chemical', 'start': 775, 'end': 784, 'mesh': 'D014810'}, {'text': 'ISO', 'type': 'Chemical', 'start': 860, 'end': 863, 'mesh': 'D007545'}, {'text': 'Ca', 'type': 'Chemical', 'start': 988, 'end': 990, 'mesh': 'D002118'}, {'text': 'Na', 'type': 'Chemical', 'start': 1072, 'end': 1074, 'mesh': 'D012964'}, {'text': 'K', 'type': 'Chemical', 'start': 1076, 'end': 1077, 'mesh': 'D011188'}, {'text': 'Mg', 'type': 'Chemical', 'start': 1090, 'end': 1092, 'mesh': 'D008274'}, {'text': 'ISO', 'type': 'Chemical', 'start': 1121, 'end': 1124, 'mesh': 'D007545'}, {'text': 'green tea', 'type': 'Chemical', 'start': 1143, 'end': 1152, 'mesh': 'D010936'}, {'text': 'vitamin E', 'type': 'Chemical', 'start': 1156, 'end': 1165, 'mesh': 'D014810'}, {'text': 'green tea', 'type': 'Chemical', 'start': 1249, 'end': 1258, 'mesh': 'D010936'}, {'text': 'vitamin E', 'type': 'Chemical', 'start': 1263, 'end': 1272, 'mesh': 'D014810'}, {'text': 'ISO', 'type': 'Chemical', 'start': 1280, 'end': 1283, 'mesh': 'D007545'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 1292, 'end': 1313, 'mesh': 'D009203'}]"
+171,19581773,Development of ocular myasthenia during pegylated interferon and ribavirin treatment for chronic hepatitis C.,"A 63-year-old male experienced sudden diplopia after 9 weeks of administration of pegylated interferon (IFN) alpha-2b and ribavirin for chronic hepatitis C (CHC). Ophthalmologic examinations showed ptosis on the right upper lid and restricted right eye movement without any other neurological signs. A brain imaging study and repetitive nerve stimulation test indicated no abnormality. The acetylcholine receptor antibody titer and response to acetylcholinesterase inhibitors were negative, and the results of thyroid function tests were normal. The patient's ophthalmological symptoms improved rapidly 3 weeks after discontinuation of pegylated IFN alpha-2b and ribavirin. The ocular myasthenia associated with combination therapy of pegylated IFN alpha-2b and ribavirin for CHC is very rarely reported; therefore, we present this case with a review of the various eye complications of IFN therapy.","[{'text': 'ocular myasthenia', 'type': 'Disease', 'start': 15, 'end': 32, 'mesh': 'D009157'}, {'text': 'pegylated interferon', 'type': 'Chemical', 'start': 40, 'end': 60, 'mesh': 'C417083'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 65, 'end': 74, 'mesh': 'D012254'}, {'text': 'chronic hepatitis C', 'type': 'Disease', 'start': 89, 'end': 108, 'mesh': 'D019698'}, {'text': 'diplopia', 'type': 'Disease', 'start': 148, 'end': 156, 'mesh': 'D004172'}, {'text': 'pegylated interferon (IFN) alpha-2b', 'type': 'Chemical', 'start': 192, 'end': 227, 'mesh': 'C417083'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 232, 'end': 241, 'mesh': 'D012254'}, {'text': 'chronic hepatitis C', 'type': 'Disease', 'start': 246, 'end': 265, 'mesh': 'D019698'}, {'text': 'CHC', 'type': 'Disease', 'start': 267, 'end': 270, 'mesh': 'D019698'}, {'text': 'ptosis on the right upper lid', 'type': 'Disease', 'start': 308, 'end': 337, 'mesh': 'D001763'}, {'text': 'restricted right eye movement', 'type': 'Disease', 'start': 342, 'end': 371, 'mesh': 'D015835'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 500, 'end': 513, 'mesh': 'D000109'}, {'text': 'pegylated IFN alpha-2b', 'type': 'Chemical', 'start': 746, 'end': 768, 'mesh': 'C417083'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 773, 'end': 782, 'mesh': 'D012254'}, {'text': 'ocular myasthenia', 'type': 'Disease', 'start': 788, 'end': 805, 'mesh': 'D009157'}, {'text': 'pegylated IFN alpha-2b', 'type': 'Chemical', 'start': 845, 'end': 867, 'mesh': 'C417083'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 872, 'end': 881, 'mesh': 'D012254'}, {'text': 'CHC', 'type': 'Disease', 'start': 886, 'end': 889, 'mesh': 'D019698'}, {'text': 'IFN', 'type': 'Chemical', 'start': 997, 'end': 1000, 'mesh': 'C417083'}]"
+172,19759529,The glycine transporter-1 inhibitor SSR103800 displays a selective and specific antipsychotic-like profile in normal and transgenic mice.,"Schizophrenia has been initially associated with dysfunction in dopamine neurotransmission. However, the observation that antagonists of the glutamate N-methyl-D-aspartate (NMDA) receptor produce schizophrenic-like symptoms in humans has led to the idea of a dysfunctioning of the glutamatergic system via its NMDA receptor. As a result, there is a growing interest in the development of pharmacological agents with potential antipsychotic properties that enhance the activity of the glutamatergic system via a modulation of the NMDA receptor. Among them are glycine transporter-1 (GlyT1) inhibitors such as SSR103800, which indirectly enhance NMDA receptor function by increasing the glycine (a co-agonist for the NMDA receptor) levels in the synapse. This study aimed at investigating the potential antipsychotic-like properties of SSR103800, with a particular focus on models of hyperactivity, involving either drug challenge (ie, amphetamine and MK-801) or transgenic mice (ie, NMDA Nr1(neo-/-) and DAT(-/-)). Results showed that SSR103800 (10-30 mg/kg p.o.) blocked hyperactivity induced by the non-competitive NMDA receptor antagonist, MK-801 and partially reversed spontaneous hyperactivity of NMDA Nr1(neo-/-) mice. In contrast, SSR103800 failed to affect hyperactivity induced by amphetamine or naturally observed in dopamine transporter (DAT(-/-)) knockout mice (10-30 mg/kg p.o.). Importantly, both classical (haloperidol) and atypical (olanzapine, clozapine and aripiprazole) antipsychotics were effective in all these models of hyperactivity. However, unlike these latter, SSR103800 did not produce catalepsy (retention on the bar test) up to 30 mg/kg p.o. Together these findings show that the GlyT1 inhibitor, SSR103800, produces antipsychotic-like effects, which differ from those observed with compounds primarily targeting the dopaminergic system, and has a reduced side-effect potential as compared with these latter drugs.","[{'text': 'glycine', 'type': 'Chemical', 'start': 4, 'end': 11, 'mesh': 'D005998'}, {'text': 'SSR103800', 'type': 'Chemical', 'start': 36, 'end': 45, 'mesh': '-1'}, {'text': 'Schizophrenia', 'type': 'Disease', 'start': 138, 'end': 151, 'mesh': 'D012559'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 202, 'end': 210, 'mesh': 'D004298'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 279, 'end': 288, 'mesh': 'D018698'}, {'text': 'N-methyl-D-aspartate', 'type': 'Chemical', 'start': 289, 'end': 309, 'mesh': 'D016202'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 311, 'end': 315, 'mesh': 'D016202'}, {'text': 'schizophrenic', 'type': 'Disease', 'start': 334, 'end': 347, 'mesh': 'D012559'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 448, 'end': 452, 'mesh': 'D016202'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 667, 'end': 671, 'mesh': 'D016202'}, {'text': 'glycine', 'type': 'Chemical', 'start': 697, 'end': 704, 'mesh': 'D005998'}, {'text': 'SSR103800', 'type': 'Chemical', 'start': 746, 'end': 755, 'mesh': '-1'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 782, 'end': 786, 'mesh': 'D016202'}, {'text': 'glycine', 'type': 'Chemical', 'start': 823, 'end': 830, 'mesh': 'D005998'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 853, 'end': 857, 'mesh': 'D016202'}, {'text': 'SSR103800', 'type': 'Chemical', 'start': 972, 'end': 981, 'mesh': '-1'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 1020, 'end': 1033, 'mesh': 'D006948'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1072, 'end': 1083, 'mesh': 'D000661'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 1088, 'end': 1094, 'mesh': 'D016291'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 1120, 'end': 1124, 'mesh': 'D016202'}, {'text': 'SSR103800', 'type': 'Chemical', 'start': 1172, 'end': 1181, 'mesh': '-1'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 1209, 'end': 1222, 'mesh': 'D006948'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 1254, 'end': 1258, 'mesh': 'D016202'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 1280, 'end': 1286, 'mesh': 'D016291'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 1322, 'end': 1335, 'mesh': 'D006948'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 1339, 'end': 1343, 'mesh': 'D016202'}, {'text': 'SSR103800', 'type': 'Chemical', 'start': 1375, 'end': 1384, 'mesh': '-1'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 1402, 'end': 1415, 'mesh': 'D006948'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1427, 'end': 1438, 'mesh': 'D000661'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1464, 'end': 1472, 'mesh': 'D004298'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1559, 'end': 1570, 'mesh': 'D006220'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 1586, 'end': 1596, 'mesh': 'C076029'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 1598, 'end': 1607, 'mesh': 'D003024'}, {'text': 'aripiprazole', 'type': 'Chemical', 'start': 1612, 'end': 1624, 'mesh': 'C094645'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 1679, 'end': 1692, 'mesh': 'D006948'}, {'text': 'SSR103800', 'type': 'Chemical', 'start': 1724, 'end': 1733, 'mesh': '-1'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 1750, 'end': 1759, 'mesh': 'D002375'}, {'text': 'SSR103800', 'type': 'Chemical', 'start': 1863, 'end': 1872, 'mesh': '-1'}]"
+173,19957053,Phenylephrine but not ephedrine reduces frontal lobe oxygenation following anesthesia-induced hypotension.,"BACKGROUND: Vasopressor agents are used to correct anesthesia-induced hypotension. We describe the effect of phenylephrine and ephedrine on frontal lobe oxygenation (S(c)O(2)) following anesthesia-induced hypotension. METHODS: Following induction of anesthesia by fentanyl (0.15 mg kg(-1)) and propofol (2.0 mg kg(-1)), 13 patients received phenylephrine (0.1 mg iv) and 12 patients received ephedrine (10 mg iv) to restore mean arterial pressure (MAP). Heart rate (HR), MAP, stroke volume (SV), cardiac output (CO), and frontal lobe oxygenation (S(c)O(2)) were registered. RESULTS: Induction of anesthesia was followed by a decrease in MAP, HR, SV, and CO concomitant with an elevation in S(c)O(2). After administration of phenylephrine, MAP increased (51 +/- 12 to 81 +/- 13 mmHg; P < 0.001; mean +/- SD). However, a 14% (from 70 +/- 8% to 60 +/- 7%) reduction in S(c)O(2) (P < 0.05) followed with no change in CO (3.7 +/- 1.1 to 3.4 +/- 0.9 l min(-1)). The administration of ephedrine led to a similar increase in MAP (53 +/- 9 to 79 +/- 8 mmHg; P < 0.001), restored CO (3.2 +/- 1.2 to 5.0 +/- 1.3 l min(-1)), and preserved S(c)O(2). CONCLUSIONS: The utilization of phenylephrine to correct hypotension induced by anesthesia has a negative impact on S(c)O(2) while ephedrine maintains frontal lobe oxygenation potentially related to an increase in CO.","[{'text': 'Phenylephrine', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'D010656'}, {'text': 'ephedrine', 'type': 'Chemical', 'start': 22, 'end': 31, 'mesh': 'D004809'}, {'text': 'reduces frontal lobe oxygenation', 'type': 'Disease', 'start': 32, 'end': 64, 'mesh': 'D002534'}, {'text': 'hypotension', 'type': 'Disease', 'start': 94, 'end': 105, 'mesh': 'D007022'}, {'text': 'hypotension', 'type': 'Disease', 'start': 177, 'end': 188, 'mesh': 'D007022'}, {'text': 'phenylephrine', 'type': 'Chemical', 'start': 216, 'end': 229, 'mesh': 'D010656'}, {'text': 'ephedrine', 'type': 'Chemical', 'start': 234, 'end': 243, 'mesh': 'D004809'}, {'text': 'hypotension', 'type': 'Disease', 'start': 312, 'end': 323, 'mesh': 'D007022'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 371, 'end': 379, 'mesh': 'D005283'}, {'text': 'propofol', 'type': 'Chemical', 'start': 401, 'end': 409, 'mesh': 'D015742'}, {'text': 'phenylephrine', 'type': 'Chemical', 'start': 448, 'end': 461, 'mesh': 'D010656'}, {'text': 'ephedrine', 'type': 'Chemical', 'start': 499, 'end': 508, 'mesh': 'D004809'}, {'text': 'stroke', 'type': 'Disease', 'start': 583, 'end': 589, 'mesh': 'D020521'}, {'text': 'phenylephrine', 'type': 'Chemical', 'start': 831, 'end': 844, 'mesh': 'D010656'}, {'text': 'ephedrine', 'type': 'Chemical', 'start': 1085, 'end': 1094, 'mesh': 'D004809'}, {'text': 'phenylephrine', 'type': 'Chemical', 'start': 1276, 'end': 1289, 'mesh': 'D010656'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1301, 'end': 1312, 'mesh': 'D007022'}, {'text': 'ephedrine', 'type': 'Chemical', 'start': 1375, 'end': 1384, 'mesh': 'D004809'}]"
+174,20619828,"A novel, multiple symptom model of obsessive-compulsive-like behaviors in animals.","BACKGROUND: Current animal models of obsessive-compulsive disorder (OCD) typically involve acute, drug-induced symptom provocation or a genetic association with stereotypies or anxiety. None of these current models demonstrate multiple OCD-like behaviors. METHODS: Neonatal rats were treated with the tricyclic antidepressant clomipramine or vehicle between days 9 and 16 twice daily and behaviorally tested in adulthood. RESULTS: Clomipramine exposure in immature rats produced significant behavioral and biochemical changes that include enhanced anxiety (elevated plus maze and marble burying), behavioral inflexibility (perseveration in the spontaneous alternation task and impaired reversal learning), working memory impairment (e.g., win-shift paradigm), hoarding, and corticostriatal dysfunction. Dopamine D2 receptors were elevated in the striatum, whereas serotonin 2C, but not serotonin 1A, receptors were elevated in the orbital frontal cortex. CONCLUSIONS: This is the first demonstration of multiple symptoms consistent with an OCD-like profile in animals. Moreover, these behaviors are accompanied by biochemical changes in brain regions previously identified as relevant to OCD. This novel model of OCD demonstrates that drug exposure during a sensitive period can program disease-like systems permanently, which could have implications for current and future therapeutic strategies for this and other psychiatric disorders.","[{'text': 'obsessive-compulsive-like behaviors', 'type': 'Disease', 'start': 35, 'end': 70, 'mesh': 'D009771'}, {'text': 'obsessive-compulsive disorder', 'type': 'Disease', 'start': 120, 'end': 149, 'mesh': 'D009771'}, {'text': 'OCD', 'type': 'Disease', 'start': 151, 'end': 154, 'mesh': 'D009771'}, {'text': 'anxiety', 'type': 'Disease', 'start': 260, 'end': 267, 'mesh': 'D001008'}, {'text': 'OCD', 'type': 'Disease', 'start': 319, 'end': 322, 'mesh': 'D009771'}, {'text': 'antidepressant', 'type': 'Chemical', 'start': 394, 'end': 408, 'mesh': 'D000928'}, {'text': 'clomipramine', 'type': 'Chemical', 'start': 409, 'end': 421, 'mesh': 'D002997'}, {'text': 'Clomipramine', 'type': 'Chemical', 'start': 514, 'end': 526, 'mesh': 'D002997'}, {'text': 'anxiety', 'type': 'Disease', 'start': 631, 'end': 638, 'mesh': 'D001008'}, {'text': 'behavioral inflexibility', 'type': 'Disease', 'start': 680, 'end': 704, 'mesh': '-1'}, {'text': 'memory impairment', 'type': 'Disease', 'start': 797, 'end': 814, 'mesh': 'D008569'}, {'text': 'hoarding', 'type': 'Disease', 'start': 843, 'end': 851, 'mesh': 'D060845'}, {'text': 'corticostriatal dysfunction', 'type': 'Disease', 'start': 857, 'end': 884, 'mesh': '-1'}, {'text': 'Dopamine', 'type': 'Chemical', 'start': 886, 'end': 894, 'mesh': 'D004298'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 947, 'end': 956, 'mesh': 'D012701'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 969, 'end': 978, 'mesh': 'D012701'}, {'text': 'OCD', 'type': 'Disease', 'start': 1123, 'end': 1126, 'mesh': 'D009771'}, {'text': 'OCD', 'type': 'Disease', 'start': 1271, 'end': 1274, 'mesh': 'D009771'}, {'text': 'OCD', 'type': 'Disease', 'start': 1296, 'end': 1299, 'mesh': 'D009771'}, {'text': 'psychiatric disorders', 'type': 'Disease', 'start': 1499, 'end': 1520, 'mesh': 'D001523'}]"
+175,891050,Late recovery of renal function in a woman with the hemolytic uremic syndrome.,"A case is reported of the hemolytic uremic syndrome (HUS) in a woman taking oral contraceptives. She was treated with heparin, dipyridamole and hemodialysis; and after more than three months, her urinary output rose above 500 ml; and six months after the onset of anuria, dialysis treatment was stopped. This case emphasizes the possibility that HUS in adults is not invariably irreversible and that, despite prolonged oliguria, recovery of renal function can be obtained. Therefore, in adult patients affected by HUS, dialysis should not be discontinued prematurely; moreover, bilateral nephrectomy, for treatment of severe hypertension and microangiopathic hemolytic anemia, should be performed with caution.","[{'text': 'hemolytic uremic syndrome', 'type': 'Disease', 'start': 52, 'end': 77, 'mesh': 'D006463'}, {'text': 'hemolytic uremic syndrome', 'type': 'Disease', 'start': 105, 'end': 130, 'mesh': 'D006463'}, {'text': 'HUS', 'type': 'Disease', 'start': 132, 'end': 135, 'mesh': 'D006463'}, {'text': 'oral contraceptives', 'type': 'Chemical', 'start': 155, 'end': 174, 'mesh': 'D003276'}, {'text': 'heparin', 'type': 'Chemical', 'start': 197, 'end': 204, 'mesh': 'D006493'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 206, 'end': 218, 'mesh': 'D004176'}, {'text': 'anuria', 'type': 'Disease', 'start': 343, 'end': 349, 'mesh': 'D001002'}, {'text': 'HUS', 'type': 'Disease', 'start': 425, 'end': 428, 'mesh': 'D006463'}, {'text': 'oliguria', 'type': 'Disease', 'start': 498, 'end': 506, 'mesh': 'D009846'}, {'text': 'HUS', 'type': 'Disease', 'start': 593, 'end': 596, 'mesh': 'D006463'}, {'text': 'hypertension', 'type': 'Disease', 'start': 704, 'end': 716, 'mesh': 'D006973'}, {'text': 'microangiopathic hemolytic anemia', 'type': 'Disease', 'start': 721, 'end': 754, 'mesh': 'D000743'}]"
+176,983936,"Effects of acetylsalicylic acid, dipyridamole, and hydrocortisone on epinephrine-induced myocardial injury in dogs.","A reproducible model for producing diffuse myocardial injury (epinephrine infusion) has been developed to study the cardioprotective effects of agents or maneuvers which might alter the evolution of acute myocardial infarction. Infusions of epinephrine (4 mug per kilogram per minute for 6 hours) increased radiocalcium uptakes into intact myocardium and each of its subcellular components with the mitochondrial fraction showing the most consistent changes when compared to saline-infused control animals (4,957 vs. 827 counts per minute per gram of dried tissue or fraction). Myocardial concentrations of calcium also increased significantly (12.0 vs. 5.0 mg.per 100 Gm. of fat-free dry weight). Infusions of calcium chloride sufficient to raise serum calcium concentrations 2 mEq. per liter failed to increase calcium influx into the myocardial cell. Mitochondrial radiocalcium uptakes were significantly decreased in animals pretreated with acetylsalicylic acid or dipyridamole or when hydrocortisone was added to the epinephrine infusion (2,682,2,803, and 3,424 counts per minute per gram of dried fraction, respectively). Myocardial calcium concentrations also were decreased (11.2, 8.3, and 8.9 mg. per 100 Gm. of fat-free dry weight, respectively) in the three treatment groups, being significantly decreased only in the last two. Evidence of microscopic damage was graded as less severe in the three treatment groups. Acetylsalicylic acid, dipyridamole, and hydrocortisone all appear to have cardioprotective effects when tested in this model.","[{'text': 'acetylsalicylic acid', 'type': 'Chemical', 'start': 11, 'end': 31, 'mesh': 'D001241'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 33, 'end': 45, 'mesh': 'D004176'}, {'text': 'hydrocortisone', 'type': 'Chemical', 'start': 51, 'end': 65, 'mesh': 'D006854'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 69, 'end': 80, 'mesh': 'D004837'}, {'text': 'myocardial injury', 'type': 'Disease', 'start': 89, 'end': 106, 'mesh': 'D009202'}, {'text': 'myocardial injury', 'type': 'Disease', 'start': 159, 'end': 176, 'mesh': 'D009202'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 178, 'end': 189, 'mesh': 'D004837'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 321, 'end': 342, 'mesh': 'D009203'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 357, 'end': 368, 'mesh': 'D004837'}, {'text': 'radiocalcium', 'type': 'Chemical', 'start': 423, 'end': 435, 'mesh': 'D002132'}, {'text': 'calcium', 'type': 'Chemical', 'start': 723, 'end': 730, 'mesh': 'D002118'}, {'text': 'calcium chloride', 'type': 'Chemical', 'start': 827, 'end': 843, 'mesh': 'D002122'}, {'text': 'calcium', 'type': 'Chemical', 'start': 870, 'end': 877, 'mesh': 'D002118'}, {'text': 'calcium', 'type': 'Chemical', 'start': 929, 'end': 936, 'mesh': 'D002118'}, {'text': 'radiocalcium', 'type': 'Chemical', 'start': 984, 'end': 996, 'mesh': 'D002132'}, {'text': 'acetylsalicylic acid', 'type': 'Chemical', 'start': 1061, 'end': 1081, 'mesh': 'D001241'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 1085, 'end': 1097, 'mesh': 'D004176'}, {'text': 'hydrocortisone', 'type': 'Chemical', 'start': 1106, 'end': 1120, 'mesh': 'D006854'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 1138, 'end': 1149, 'mesh': 'D004837'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1255, 'end': 1262, 'mesh': 'D002118'}, {'text': 'Acetylsalicylic acid', 'type': 'Chemical', 'start': 1543, 'end': 1563, 'mesh': 'D001241'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 1565, 'end': 1577, 'mesh': 'D004176'}, {'text': 'hydrocortisone', 'type': 'Chemical', 'start': 1583, 'end': 1597, 'mesh': 'D006854'}]"
+177,1428568,Changes in depressive status associated with topical beta-blockers.,"Depression and sexual dysfunction have been related to side effects of topical beta-blockers. We performed a preliminary study in order to determine any difference between a non selective beta-blocker (timolol) and a selective beta-blocker (betaxolol) regarding CNS side effects. Eight glaucomatous patients chronically treated with timolol 0.5%/12h, suffering from depression diagnosed through DMS-III-R criteria, were included in the study. During the six-month follow up, depression was quantified through the Beck and Zung-Conde scales every two months. In a double blind cross-over study with control group, the patients under timolol treatment presented higher depression values measured through the Beck and the Zung-Conde scales (p < 0.001 vs control). These results suggest that betaxolol could be less of a depression-inducer than timolol in predisposed patients.","[{'text': 'depressive', 'type': 'Disease', 'start': 11, 'end': 21, 'mesh': 'D003866'}, {'text': 'Depression', 'type': 'Disease', 'start': 68, 'end': 78, 'mesh': 'D003866'}, {'text': 'sexual dysfunction', 'type': 'Disease', 'start': 83, 'end': 101, 'mesh': 'D012735'}, {'text': 'timolol', 'type': 'Chemical', 'start': 270, 'end': 277, 'mesh': 'D013999'}, {'text': 'betaxolol', 'type': 'Chemical', 'start': 309, 'end': 318, 'mesh': 'D015784'}, {'text': 'glaucomatous', 'type': 'Disease', 'start': 354, 'end': 366, 'mesh': 'D005901'}, {'text': 'timolol', 'type': 'Chemical', 'start': 401, 'end': 408, 'mesh': 'D013999'}, {'text': 'depression', 'type': 'Disease', 'start': 434, 'end': 444, 'mesh': 'D003866'}, {'text': 'depression', 'type': 'Disease', 'start': 543, 'end': 553, 'mesh': 'D003866'}, {'text': 'timolol', 'type': 'Chemical', 'start': 700, 'end': 707, 'mesh': 'D013999'}, {'text': 'depression', 'type': 'Disease', 'start': 735, 'end': 745, 'mesh': 'D003866'}, {'text': 'betaxolol', 'type': 'Chemical', 'start': 856, 'end': 865, 'mesh': 'D015784'}, {'text': 'depression', 'type': 'Disease', 'start': 885, 'end': 895, 'mesh': 'D003866'}, {'text': 'timolol', 'type': 'Chemical', 'start': 909, 'end': 916, 'mesh': 'D013999'}]"
+178,1720453,Long-term follow-up of ifosfamide renal toxicity in children treated for malignant mesenchymal tumors: an International Society of Pediatric Oncology report.,"The renal function of 74 children with malignant mesenchymal tumors in complete remission and who have received the same ifosfamide chemotherapy protocol (International Society of Pediatric Oncology Malignant Mesenchymal Tumor Study 84 [SIOP MMT 84]) were studied 1 year after the completion of treatment. Total cumulative doses were 36 or 60 g/m2 of ifosfamide (six or 10 cycles of ifosfamide, vincristine, and dactinomycin [IVA]). None of them had received cisplatin chemotherapy. Ages ranged from 4 months to 17 years; 58 patients were males and 42 females. The most common primary tumor site was the head and neck. Renal function was investigated by measuring plasma and urinary electrolytes, glucosuria, proteinuria, aminoaciduria, urinary pH, osmolarity, creatinine clearance, phosphate tubular reabsorption, beta 2 microglobulinuria, and lysozymuria. Fifty-eight patients (78%) had normal renal tests, whereas 16 patients (22%) had renal abnormalities. Two subsets of patients were identified from this latter group: the first included four patients (5% of the total population) who developed major toxicity resulting in Fanconi's syndrome (TDFS); and the second group included five patients with elevated beta 2 microglobulinuria and low phosphate reabsorption. The remaining seven patients had isolated beta 2 microglobulinuria. Severe toxicity was correlated with the higher cumulative dose of 60 g/m2 of ifosfamide, a younger age (less than 2 1/2 years old), and a predominance of vesicoprostatic tumor involvement. This low percentage (5%) of TDFS must be evaluated with respect to the efficacy of ifosfamide in the treatment of mesenchymal tumors in children.","[{'text': 'ifosfamide', 'type': 'Chemical', 'start': 23, 'end': 33, 'mesh': 'D007069'}, {'text': 'renal toxicity', 'type': 'Disease', 'start': 34, 'end': 48, 'mesh': 'D007674'}, {'text': 'malignant mesenchymal tumors', 'type': 'Disease', 'start': 73, 'end': 101, 'mesh': 'C535700'}, {'text': 'malignant mesenchymal tumors', 'type': 'Disease', 'start': 197, 'end': 225, 'mesh': 'C535700'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 279, 'end': 289, 'mesh': 'D007069'}, {'text': 'Malignant Mesenchymal Tumor', 'type': 'Disease', 'start': 357, 'end': 384, 'mesh': 'C535700'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 509, 'end': 519, 'mesh': 'D007069'}, {'text': 'ifosfamide, vincristine, and dactinomycin', 'type': 'Chemical', 'start': 541, 'end': 582, 'mesh': 'C064227'}, {'text': 'IVA', 'type': 'Chemical', 'start': 584, 'end': 587, 'mesh': 'C064227'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 617, 'end': 626, 'mesh': 'D002945'}, {'text': 'tumor', 'type': 'Disease', 'start': 743, 'end': 748, 'mesh': 'D009369'}, {'text': 'glucosuria', 'type': 'Disease', 'start': 855, 'end': 865, 'mesh': 'D006030'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 867, 'end': 878, 'mesh': 'D011507'}, {'text': 'aminoaciduria', 'type': 'Disease', 'start': 880, 'end': 893, 'mesh': 'D000608'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 919, 'end': 929, 'mesh': 'D003404'}, {'text': 'phosphate', 'type': 'Chemical', 'start': 941, 'end': 950, 'mesh': 'D010710'}, {'text': 'renal abnormalities', 'type': 'Disease', 'start': 1097, 'end': 1116, 'mesh': 'D007674'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1264, 'end': 1272, 'mesh': 'D064420'}, {'text': ""Fanconi's syndrome"", 'type': 'Disease', 'start': 1286, 'end': 1304, 'mesh': 'D005198'}, {'text': 'TDFS', 'type': 'Disease', 'start': 1306, 'end': 1310, 'mesh': 'D005198'}, {'text': 'phosphate', 'type': 'Chemical', 'start': 1404, 'end': 1413, 'mesh': 'D010710'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1503, 'end': 1511, 'mesh': 'D064420'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 1573, 'end': 1583, 'mesh': 'D007069'}, {'text': 'tumor', 'type': 'Disease', 'start': 1666, 'end': 1671, 'mesh': 'D009369'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 1768, 'end': 1778, 'mesh': 'D007069'}, {'text': 'mesenchymal tumors', 'type': 'Disease', 'start': 1799, 'end': 1817, 'mesh': 'C535700'}]"
+179,1833784,Evidence for an involvement of D1 and D2 dopamine receptors in mediating nicotine-induced hyperactivity in rats.,"Previous studies have suggested that repeated exposure of rats to the drug or to the experimental environment is necessary to observe nicotine-induced locomotor stimulation. In the present study the role of habituation to the experimental environment on the stimulant effect of nicotine in rats was examined. In addition, the role of dopamine receptors in mediating nicotine-induced locomotor stimulation was investigated by examining the effects of selective D1 and D2 dopamine receptor antagonists on activity induced by nicotine. Locomotor activity was assessed in male Sprague-Dawley rats tested in photocell cages. Nicotine (1.0 mg/kg) caused a significant increase in locomotor activity in rats that were habituated to the test environment, but had only a weak and delayed stimulant action in rats that were unfamiliar with the test environment. The stimulant action of nicotine was blocked by the central nicotinic antagonist mecamylamine but not by the peripheral nicotinic blocker hexamethonium, indicating that the response is probably mediated by central nicotinic receptors. Nicotine-induced hyperactivity was blocked by the selective D1 antagonist SCH 23390, the selective D2 antagonist raclopride and the D1/D2 antagonist fluphenazine. Pretreatment with the D2 agonist PHNO enhanced nicotine-induced hyperactivity, whereas the D1 agonist SKF 38393 had no effect. The results indicate that acute nicotine injection induces a pronounced hyperactivity in rats habituated to the test environment. The effect appears to be mediated by central nicotine receptors, possibly located on dopaminergic neurons, and also requires the activation of both D1 and D2 dopamine receptors.","[{'text': 'dopamine', 'type': 'Chemical', 'start': 41, 'end': 49, 'mesh': 'D004298'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 73, 'end': 81, 'mesh': 'D009538'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 90, 'end': 103, 'mesh': 'D006948'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 247, 'end': 255, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 391, 'end': 399, 'mesh': 'D009538'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 447, 'end': 455, 'mesh': 'D004298'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 479, 'end': 487, 'mesh': 'D009538'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 583, 'end': 591, 'mesh': 'D004298'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 636, 'end': 644, 'mesh': 'D009538'}, {'text': 'Nicotine', 'type': 'Chemical', 'start': 733, 'end': 741, 'mesh': 'D009538'}, {'text': 'increase in locomotor activity', 'type': 'Disease', 'start': 775, 'end': 805, 'mesh': 'D006948'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 989, 'end': 997, 'mesh': 'D009538'}, {'text': 'mecamylamine', 'type': 'Chemical', 'start': 1046, 'end': 1058, 'mesh': 'D008464'}, {'text': 'hexamethonium', 'type': 'Chemical', 'start': 1103, 'end': 1116, 'mesh': 'D018738'}, {'text': 'Nicotine', 'type': 'Chemical', 'start': 1200, 'end': 1208, 'mesh': 'D009538'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 1217, 'end': 1230, 'mesh': 'D006948'}, {'text': 'SCH 23390', 'type': 'Chemical', 'start': 1274, 'end': 1283, 'mesh': 'C534628'}, {'text': 'raclopride', 'type': 'Chemical', 'start': 1313, 'end': 1323, 'mesh': 'D020891'}, {'text': 'fluphenazine', 'type': 'Chemical', 'start': 1349, 'end': 1361, 'mesh': 'D005476'}, {'text': 'PHNO', 'type': 'Chemical', 'start': 1396, 'end': 1400, 'mesh': '-1'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 1410, 'end': 1418, 'mesh': 'D009538'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 1427, 'end': 1440, 'mesh': 'D006948'}, {'text': 'SKF 38393', 'type': 'Chemical', 'start': 1465, 'end': 1474, 'mesh': 'D015647'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 1522, 'end': 1530, 'mesh': 'D009538'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 1562, 'end': 1575, 'mesh': 'D006948'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 1665, 'end': 1673, 'mesh': 'D009538'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1778, 'end': 1786, 'mesh': 'D004298'}]"
+180,1867351,Neuropsychiatric side effects after the use of mefloquine.,"This study describes neuropsychiatric side effects in patients after treatment with mefloquine. Reactions consisted mainly of seizures, acute psychoses, anxiety neurosis, and major disturbances of sleep-wake rhythm. Side effects occurred after both therapeutic and prophylactic intake and were graded from moderate to severe. In a risk analysis of neuropsychiatric side effects in Germany, it is estimated that one of 8,000 mefloquine users suffers from such reactions. The incidence calculation revealed that one of 215 therapeutic users had reactions, compared with one of 13,000 in the prophylaxis group, making the risk of neuropsychiatric reactions after mefloquine treatment 60 times higher than after prophylaxis. Therefore, certain limitations for malaria prophylaxis and treatment with mefloquine are recommended.","[{'text': 'mefloquine', 'type': 'Chemical', 'start': 47, 'end': 57, 'mesh': 'D015767'}, {'text': 'mefloquine', 'type': 'Chemical', 'start': 143, 'end': 153, 'mesh': 'D015767'}, {'text': 'seizures', 'type': 'Disease', 'start': 185, 'end': 193, 'mesh': 'D012640'}, {'text': 'psychoses', 'type': 'Disease', 'start': 201, 'end': 210, 'mesh': 'D011605'}, {'text': 'anxiety neurosis', 'type': 'Disease', 'start': 212, 'end': 228, 'mesh': 'D001008'}, {'text': 'disturbances of sleep-wake rhythm', 'type': 'Disease', 'start': 240, 'end': 273, 'mesh': 'D012893'}, {'text': 'mefloquine', 'type': 'Chemical', 'start': 483, 'end': 493, 'mesh': 'D015767'}, {'text': 'mefloquine', 'type': 'Chemical', 'start': 719, 'end': 729, 'mesh': 'D015767'}, {'text': 'malaria', 'type': 'Disease', 'start': 815, 'end': 822, 'mesh': 'D008288'}, {'text': 'mefloquine', 'type': 'Chemical', 'start': 854, 'end': 864, 'mesh': 'D015767'}]"
+181,2070391,Reduction in injection pain using buffered lidocaine as a local anesthetic before cardiac catheterization.,"Previous reports have suggested that pain associated with the injection of lidocaine is related to the acidic pH of the solution. To determine if the addition of a buffering solution to adjust the pH of lidocaine into the physiologic range would reduce pain during injection, we performed a blinded randomized study in patients undergoing cardiac catheterization. Twenty patients were asked to quantify the severity of pain after receiving standard lidocaine in one femoral area and buffered lidocaine in the opposite femoral area. The mean pain score for buffered lidocaine was significantly lower than the mean score for standard lidocaine (2.7 +/- 1.9 vs. 3.8 +/- 2.2, P = 0.03). The pH adjustment of standard lidocaine can be accomplished easily in the catheterization laboratory before injection and results in a reduction of the pain occurring during the infiltration of tissues.","[{'text': 'pain', 'type': 'Disease', 'start': 23, 'end': 27, 'mesh': 'D010146'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 43, 'end': 52, 'mesh': 'D008012'}, {'text': 'pain', 'type': 'Disease', 'start': 144, 'end': 148, 'mesh': 'D010146'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 182, 'end': 191, 'mesh': 'D008012'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 310, 'end': 319, 'mesh': 'D008012'}, {'text': 'pain', 'type': 'Disease', 'start': 360, 'end': 364, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 526, 'end': 530, 'mesh': 'D010146'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 556, 'end': 565, 'mesh': 'D008012'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 599, 'end': 608, 'mesh': 'D008012'}, {'text': 'pain', 'type': 'Disease', 'start': 648, 'end': 652, 'mesh': 'D010146'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 672, 'end': 681, 'mesh': 'D008012'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 739, 'end': 748, 'mesh': 'D008012'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 820, 'end': 829, 'mesh': 'D008012'}, {'text': 'pain', 'type': 'Disease', 'start': 942, 'end': 946, 'mesh': 'D010146'}]"
+182,2266990,"Randomized, double-blind trial of mazindol in Duchenne dystrophy.","There is evidence that growth hormone may be related to the progression of weakness in Duchenne dystrophy. We conducted a 12-month controlled trial of mazindol, a putative growth hormone secretion inhibitor, in 83 boys with Duchenne dystrophy. Muscle strength, contractures, functional ability and pulmonary function were tested at baseline, and 6 and 12 months after treatment with mazindol (3 mg/d) or placebo. The study was designed to have a power of greater than 0.90 to detect a slowing to 25% of the expected rate of progression of weakness at P less than 0.05. Mazindol did not benefit strength at any point in the study. Side effects attributable to mazindol included decreased appetite (36%), dry mouth (10%), behavioral change (22%), and gastrointestinal symptoms (18%); mazindol dosage was reduced in 43% of patients. The effect of mazindol on GH secretion was estimated indirectly by comparing the postabsorptive IGF-I levels obtained following 3, 6, 9, and 12 months in the mazindol treated to those in the placebo groups. Although mazindol-treated patients gained less weight and height than placebo-treated patients, no significant effect on IGF-I levels was observed. Mazindol doses not slow the progression of weakness in Duchenne dystrophy.","[{'text': 'mazindol', 'type': 'Chemical', 'start': 34, 'end': 42, 'mesh': 'D008454'}, {'text': 'Duchenne dystrophy', 'type': 'Disease', 'start': 46, 'end': 64, 'mesh': 'D020388'}, {'text': 'weakness', 'type': 'Disease', 'start': 141, 'end': 149, 'mesh': 'D018908'}, {'text': 'Duchenne dystrophy', 'type': 'Disease', 'start': 153, 'end': 171, 'mesh': 'D020388'}, {'text': 'mazindol', 'type': 'Chemical', 'start': 217, 'end': 225, 'mesh': 'D008454'}, {'text': 'Duchenne dystrophy', 'type': 'Disease', 'start': 290, 'end': 308, 'mesh': 'D020388'}, {'text': 'mazindol', 'type': 'Chemical', 'start': 449, 'end': 457, 'mesh': 'D008454'}, {'text': 'weakness', 'type': 'Disease', 'start': 605, 'end': 613, 'mesh': 'D018908'}, {'text': 'Mazindol', 'type': 'Chemical', 'start': 635, 'end': 643, 'mesh': 'D008454'}, {'text': 'mazindol', 'type': 'Chemical', 'start': 725, 'end': 733, 'mesh': 'D008454'}, {'text': 'decreased appetite', 'type': 'Disease', 'start': 743, 'end': 761, 'mesh': 'D001068'}, {'text': 'dry mouth', 'type': 'Disease', 'start': 769, 'end': 778, 'mesh': 'D014987'}, {'text': 'gastrointestinal symptoms', 'type': 'Disease', 'start': 815, 'end': 840, 'mesh': 'D012817'}, {'text': 'mazindol', 'type': 'Chemical', 'start': 848, 'end': 856, 'mesh': 'D008454'}, {'text': 'mazindol', 'type': 'Chemical', 'start': 910, 'end': 918, 'mesh': 'D008454'}, {'text': 'mazindol', 'type': 'Chemical', 'start': 1054, 'end': 1062, 'mesh': 'D008454'}, {'text': 'mazindol', 'type': 'Chemical', 'start': 1112, 'end': 1120, 'mesh': 'D008454'}, {'text': 'Mazindol', 'type': 'Chemical', 'start': 1251, 'end': 1259, 'mesh': 'D008454'}, {'text': 'weakness', 'type': 'Disease', 'start': 1294, 'end': 1302, 'mesh': 'D018908'}, {'text': 'Duchenne dystrophy', 'type': 'Disease', 'start': 1306, 'end': 1324, 'mesh': 'D020388'}]"
+183,2348231,Pentoxifylline (Trental) does not inhibit dipyridamole-induced coronary hyperemia: implications for dipyridamole-thallium-201 myocardial imaging.,"Dipyridamole-thallium-201 imaging is often performed in patients unable to exercise because of peripheral vascular disease. Many of these patients are taking pentoxifylline (Trental), a methylxanthine derivative which may improve intermittent claudication. Whether pentoxifylline inhibits dipyridamole-induced coronary hyperemia like other methylxanthines such as theophylline and should be stopped prior to dipyridamole-thallium-201 imaging is unknown. Therefore, we studied the hyperemic response to dipyridamole in seven open-chest anesthetized dogs after pretreatment with either pentoxifylline (0, 7.5, or 15 mg/kg i.v.) or theophylline (3 mg/kg i.v.). Baseline circumflex coronary blood flows did not differ significantly among treatment groups. Dipyridamole significantly increased coronary blood flow before and after 7.5 or 15 mm/kg i.v. pentoxifylline (p less than 0.002). Neither dose of pentoxifylline significantly decreased the dipyridamole-induced hyperemia, while peak coronary blood flow was significantly lower after theophylline (p less than 0.01). We conclude that pentoxyifylline does not inhibit dipyridamole-induced coronary hyperemia even at high doses.","[{'text': 'Pentoxifylline', 'type': 'Chemical', 'start': 0, 'end': 14, 'mesh': 'D010431'}, {'text': 'Trental', 'type': 'Chemical', 'start': 16, 'end': 23, 'mesh': 'D010431'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 42, 'end': 54, 'mesh': 'D004176'}, {'text': 'hyperemia', 'type': 'Disease', 'start': 72, 'end': 81, 'mesh': 'D006940'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 100, 'end': 112, 'mesh': 'D004176'}, {'text': 'thallium', 'type': 'Chemical', 'start': 113, 'end': 121, 'mesh': 'D013793'}, {'text': 'Dipyridamole', 'type': 'Chemical', 'start': 146, 'end': 158, 'mesh': 'D004176'}, {'text': 'thallium', 'type': 'Chemical', 'start': 159, 'end': 167, 'mesh': 'D013793'}, {'text': 'peripheral vascular disease', 'type': 'Disease', 'start': 241, 'end': 268, 'mesh': 'D016491'}, {'text': 'pentoxifylline', 'type': 'Chemical', 'start': 304, 'end': 318, 'mesh': 'D010431'}, {'text': 'Trental', 'type': 'Chemical', 'start': 320, 'end': 327, 'mesh': 'D010431'}, {'text': 'methylxanthine', 'type': 'Chemical', 'start': 332, 'end': 346, 'mesh': 'C008514'}, {'text': 'intermittent claudication', 'type': 'Disease', 'start': 376, 'end': 401, 'mesh': 'D007383'}, {'text': 'pentoxifylline', 'type': 'Chemical', 'start': 411, 'end': 425, 'mesh': 'D010431'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 435, 'end': 447, 'mesh': 'D004176'}, {'text': 'hyperemia', 'type': 'Disease', 'start': 465, 'end': 474, 'mesh': 'D006940'}, {'text': 'methylxanthines', 'type': 'Chemical', 'start': 486, 'end': 501, 'mesh': 'C008514'}, {'text': 'theophylline', 'type': 'Chemical', 'start': 510, 'end': 522, 'mesh': 'D013806'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 554, 'end': 566, 'mesh': 'D004176'}, {'text': 'thallium', 'type': 'Chemical', 'start': 567, 'end': 575, 'mesh': 'D013793'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 648, 'end': 660, 'mesh': 'D004176'}, {'text': 'pentoxifylline', 'type': 'Chemical', 'start': 730, 'end': 744, 'mesh': 'D010431'}, {'text': 'theophylline', 'type': 'Chemical', 'start': 775, 'end': 787, 'mesh': 'D013806'}, {'text': 'Dipyridamole', 'type': 'Chemical', 'start': 898, 'end': 910, 'mesh': 'D004176'}, {'text': 'pentoxifylline', 'type': 'Chemical', 'start': 993, 'end': 1007, 'mesh': 'D010431'}, {'text': 'pentoxifylline', 'type': 'Chemical', 'start': 1045, 'end': 1059, 'mesh': 'D010431'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 1088, 'end': 1100, 'mesh': 'D004176'}, {'text': 'hyperemia', 'type': 'Disease', 'start': 1109, 'end': 1118, 'mesh': 'D006940'}, {'text': 'theophylline', 'type': 'Chemical', 'start': 1181, 'end': 1193, 'mesh': 'D013806'}, {'text': 'pentoxyifylline', 'type': 'Chemical', 'start': 1231, 'end': 1246, 'mesh': 'D010431'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 1264, 'end': 1276, 'mesh': 'D004176'}, {'text': 'hyperemia', 'type': 'Disease', 'start': 1294, 'end': 1303, 'mesh': 'D006940'}]"
+184,2355241,Cause of death among patients with Parkinson's disease: a rare mortality due to cerebral haemorrhage.,"Causes of death, with special reference to cerebral haemorrhage, among 240 patients with pathologically verified Parkinson's disease were investigated using the Annuals of the Pathological Autopsy Cases in Japan from 1981 to 1985. The leading causes of death were pneumonia and bronchitis (44.1%), malignant neoplasms (11.6%), heart diseases (4.1%), cerebral infarction (3.7%) and septicaemia (3.3%). Cerebral haemorrhage was the 11th most frequent cause of death, accounting for only 0.8% of deaths among the patients, whereas it was the 5th most common cause of death among the Japanese general population in 1985. The low incidence of cerebral haemorrhage as a cause of death in patients with Parkinson's disease may reflect the hypotensive effect of levodopa and a hypotensive mechanism due to reduced noradrenaline levels in the parkinsonian brain.","[{'text': 'death', 'type': 'Disease', 'start': 9, 'end': 14, 'mesh': 'D003643'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 35, 'end': 54, 'mesh': 'D010300'}, {'text': 'cerebral haemorrhage', 'type': 'Disease', 'start': 80, 'end': 100, 'mesh': 'D002543'}, {'text': 'death', 'type': 'Disease', 'start': 112, 'end': 117, 'mesh': 'D003643'}, {'text': 'cerebral haemorrhage', 'type': 'Disease', 'start': 145, 'end': 165, 'mesh': 'D002543'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 215, 'end': 234, 'mesh': 'D010300'}, {'text': 'death', 'type': 'Disease', 'start': 355, 'end': 360, 'mesh': 'D003643'}, {'text': 'pneumonia', 'type': 'Disease', 'start': 366, 'end': 375, 'mesh': 'D011014'}, {'text': 'bronchitis', 'type': 'Disease', 'start': 380, 'end': 390, 'mesh': 'D001991'}, {'text': 'neoplasms', 'type': 'Disease', 'start': 410, 'end': 419, 'mesh': 'D009369'}, {'text': 'heart diseases', 'type': 'Disease', 'start': 429, 'end': 443, 'mesh': 'D006331'}, {'text': 'cerebral infarction', 'type': 'Disease', 'start': 452, 'end': 471, 'mesh': 'D002544'}, {'text': 'septicaemia', 'type': 'Disease', 'start': 483, 'end': 494, 'mesh': 'D018805'}, {'text': 'Cerebral haemorrhage', 'type': 'Disease', 'start': 503, 'end': 523, 'mesh': 'D002543'}, {'text': 'death', 'type': 'Disease', 'start': 560, 'end': 565, 'mesh': 'D003643'}, {'text': 'deaths', 'type': 'Disease', 'start': 595, 'end': 601, 'mesh': 'D003643'}, {'text': 'death', 'type': 'Disease', 'start': 666, 'end': 671, 'mesh': 'D003643'}, {'text': 'cerebral haemorrhage', 'type': 'Disease', 'start': 740, 'end': 760, 'mesh': 'D002543'}, {'text': 'death', 'type': 'Disease', 'start': 775, 'end': 780, 'mesh': 'D003643'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 798, 'end': 817, 'mesh': 'D010300'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 834, 'end': 845, 'mesh': 'D007022'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 856, 'end': 864, 'mesh': 'D007980'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 871, 'end': 882, 'mesh': 'D007022'}, {'text': 'noradrenaline', 'type': 'Chemical', 'start': 908, 'end': 921, 'mesh': 'D009638'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 936, 'end': 948, 'mesh': 'D010300'}]"
+185,2445283,Tolerance and antiviral effect of ribavirin in patients with Argentine hemorrhagic fever.,"Tolerance and antiviral effect of ribavirin was studied in 6 patients with Argentine hemorrhagic fever (AHF) of more than 8 days of evolution. Administration of ribavirin resulted in a neutralization of viremia and a drop of endogenous interferon titers. The average time of death was delayed. A reversible anemia was the only adverse effect observed. From these results, we conclude that ribavirin has an antiviral effect in advanced cases of AHF, and that anemia, the only secondary reaction observed, can be easily managed. The possible beneficial effect of ribavirin during the initial days of AHF is discussed.","[{'text': 'ribavirin', 'type': 'Chemical', 'start': 34, 'end': 43, 'mesh': 'D012254'}, {'text': 'Argentine hemorrhagic fever', 'type': 'Disease', 'start': 61, 'end': 88, 'mesh': 'D006478'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 124, 'end': 133, 'mesh': 'D012254'}, {'text': 'Argentine hemorrhagic fever', 'type': 'Disease', 'start': 165, 'end': 192, 'mesh': 'D006478'}, {'text': 'AHF', 'type': 'Disease', 'start': 194, 'end': 197, 'mesh': 'D006478'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 251, 'end': 260, 'mesh': 'D012254'}, {'text': 'viremia', 'type': 'Disease', 'start': 293, 'end': 300, 'mesh': 'D014766'}, {'text': 'death', 'type': 'Disease', 'start': 365, 'end': 370, 'mesh': 'D003643'}, {'text': 'anemia', 'type': 'Disease', 'start': 397, 'end': 403, 'mesh': 'D000740'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 479, 'end': 488, 'mesh': 'D012254'}, {'text': 'AHF', 'type': 'Disease', 'start': 534, 'end': 537, 'mesh': 'D006478'}, {'text': 'anemia', 'type': 'Disease', 'start': 548, 'end': 554, 'mesh': 'D000740'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 651, 'end': 660, 'mesh': 'D012254'}, {'text': 'AHF', 'type': 'Disease', 'start': 688, 'end': 691, 'mesh': 'D006478'}]"
+186,2950248,Dipyridamole-induced myocardial ischemia.,"Angina and ischemic electrocardiographic changes occurred after administration of oral dipyridamole in four patients awaiting urgent myocardial revascularization procedures. To our knowledge, this has not previously been reported as a side effect of preoperative dipyridamole therapy, although dipyridamole-induced myocardial ischemia has been demonstrated to occur in animals and humans with coronary artery disease. Epicardial coronary collateral vessels were demonstrated in all four patients; a coronary ""steal"" phenomenon may be the mechanism of the dipyridamole-induced ischemia observed.","[{'text': 'Dipyridamole', 'type': 'Chemical', 'start': 0, 'end': 12, 'mesh': 'D004176'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 21, 'end': 40, 'mesh': 'D017202'}, {'text': 'Angina', 'type': 'Disease', 'start': 42, 'end': 48, 'mesh': 'D000787'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 129, 'end': 141, 'mesh': 'D004176'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 305, 'end': 317, 'mesh': 'D004176'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 336, 'end': 348, 'mesh': 'D004176'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 357, 'end': 376, 'mesh': 'D017202'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 435, 'end': 458, 'mesh': 'D003324'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 597, 'end': 609, 'mesh': 'D004176'}, {'text': 'ischemia', 'type': 'Disease', 'start': 618, 'end': 626, 'mesh': 'D007511'}]"
+187,3015567,Inhibition of immunoreactive corticotropin-releasing factor secretion into the hypophysial-portal circulation by delayed glucocorticoid feedback.,"Nitroprusside-induced hypotension evokes ACTH secretion which is primarily mediated by enhanced secretion of immunoreactive corticotropin-releasing factor (irCRF) into the hypophysial-portal circulation. Portal plasma concentrations of neither arginine vasopressin nor oxytocin are significantly altered in this paradigm. Application of a delayed feedback signal, in the form of a 2-h systemic corticosterone infusion in urethane-anesthetized rats with pharmacological blockade of glucocorticoid synthesis, is without effect on the resting secretion of arginine vasopressin and oxytocin at any corticosterone feedback dose tested. Resting irCRF levels are suppressed only at the highest corticosterone infusion rate, which resulted in systemic corticosterone levels of 40 micrograms/dl. Suppression of irCRF secretion in response to nitroprusside-induced hypotension is observed and occurs at a plasma corticosterone level between 8-12 micrograms/dl. These studies provide further evidence for a strong central component of the delayed feedback process which is mediated by modulation of irCRF release.","[{'text': 'Nitroprusside', 'type': 'Chemical', 'start': 146, 'end': 159, 'mesh': 'D009599'}, {'text': 'hypotension', 'type': 'Disease', 'start': 168, 'end': 179, 'mesh': 'D007022'}, {'text': 'arginine vasopressin', 'type': 'Chemical', 'start': 390, 'end': 410, 'mesh': 'D001127'}, {'text': 'oxytocin', 'type': 'Chemical', 'start': 415, 'end': 423, 'mesh': 'D010121'}, {'text': 'corticosterone', 'type': 'Chemical', 'start': 540, 'end': 554, 'mesh': 'D003345'}, {'text': 'urethane', 'type': 'Chemical', 'start': 567, 'end': 575, 'mesh': 'D014520'}, {'text': 'arginine vasopressin', 'type': 'Chemical', 'start': 699, 'end': 719, 'mesh': 'D001127'}, {'text': 'oxytocin', 'type': 'Chemical', 'start': 724, 'end': 732, 'mesh': 'D010121'}, {'text': 'corticosterone', 'type': 'Chemical', 'start': 740, 'end': 754, 'mesh': 'D003345'}, {'text': 'corticosterone', 'type': 'Chemical', 'start': 833, 'end': 847, 'mesh': 'D003345'}, {'text': 'corticosterone', 'type': 'Chemical', 'start': 890, 'end': 904, 'mesh': 'D003345'}, {'text': 'nitroprusside', 'type': 'Chemical', 'start': 979, 'end': 992, 'mesh': 'D009599'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1001, 'end': 1012, 'mesh': 'D007022'}, {'text': 'corticosterone', 'type': 'Chemical', 'start': 1048, 'end': 1062, 'mesh': 'D003345'}]"
+188,3031535,Noradrenergic involvement in catalepsy induced by delta 9-tetrahydrocannabinol.,"In order to elucidate the role of the catecholaminergic system in the cataleptogenic effect of delta 9-tetrahydrocannabinol (THC), the effect of pretreatment with 6-hydroxydopamine (6-OHDA) or with desipramine and 6-OHDA and lesions of the locus coeruleus were investigated in rats. The cataleptogenic effect of THC was significantly reduced in rats treated with 6-OHDA and in rats with lesions of the locus coeruleus but not in rats treated with desipramine and 6-OHDA, as compared with control rats. On the contrary, the cataleptogenic effect of haloperidol was significantly reduced in rats treated with desipramine and 6-OHDA but not in rats treated with 6-OHDA or in rats with lesions of the locus coeruleus. These results indicate that noradrenergic neurons have an important role in the manifestation of catalepsy induced by THC, whereas dopaminergic neurons are important in catalepsy induced by haloperidol.","[{'text': 'catalepsy', 'type': 'Disease', 'start': 29, 'end': 38, 'mesh': 'D002375'}, {'text': 'delta 9-tetrahydrocannabinol', 'type': 'Chemical', 'start': 50, 'end': 78, 'mesh': 'D013759'}, {'text': 'delta 9-tetrahydrocannabinol', 'type': 'Chemical', 'start': 175, 'end': 203, 'mesh': 'D013759'}, {'text': 'THC', 'type': 'Chemical', 'start': 205, 'end': 208, 'mesh': 'D013759'}, {'text': '6-hydroxydopamine', 'type': 'Chemical', 'start': 243, 'end': 260, 'mesh': 'D016627'}, {'text': '6-OHDA', 'type': 'Chemical', 'start': 262, 'end': 268, 'mesh': 'D016627'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 278, 'end': 289, 'mesh': 'D003891'}, {'text': '6-OHDA', 'type': 'Chemical', 'start': 294, 'end': 300, 'mesh': 'D016627'}, {'text': 'THC', 'type': 'Chemical', 'start': 392, 'end': 395, 'mesh': 'D013759'}, {'text': '6-OHDA', 'type': 'Chemical', 'start': 443, 'end': 449, 'mesh': 'D016627'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 527, 'end': 538, 'mesh': 'D003891'}, {'text': '6-OHDA', 'type': 'Chemical', 'start': 543, 'end': 549, 'mesh': 'D016627'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 628, 'end': 639, 'mesh': 'D006220'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 687, 'end': 698, 'mesh': 'D003891'}, {'text': '6-OHDA', 'type': 'Chemical', 'start': 703, 'end': 709, 'mesh': 'D016627'}, {'text': '6-OHDA', 'type': 'Chemical', 'start': 739, 'end': 745, 'mesh': 'D016627'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 891, 'end': 900, 'mesh': 'D002375'}, {'text': 'THC', 'type': 'Chemical', 'start': 912, 'end': 915, 'mesh': 'D013759'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 963, 'end': 972, 'mesh': 'D002375'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 984, 'end': 995, 'mesh': 'D006220'}]"
+189,3125768,Intracranial pressure increases during alfentanil-induced rigidity.,"Intracranial pressure (ICP) was measured during alfentanil-induced rigidity in rats. Ten rats had arterial, central venous (CVP), and subdural cannulae inserted under halothane anesthesia. The animals were mechanically ventilated to achieve normocarbia (PCO2 = 42 +/- 1 mmHg, mean +/- SE). Following instrumentation, halothane was discontinued and alfentanil (125 mu/kg) administered iv during emergence from halothane anesthesia. In the five rats that developed somatic rigidity, ICP and CVP increased significantly above baseline (delta ICP 7.5 +/- 1.0 mmHg, delta CVP 5.9 +/- 1.3 mmHg). These variables returned to baseline when rigidity was abolished with metocurine. In five rats that did not become rigid, ICP and CVP did not change following alfentanil. These observations suggest that rigidity should be prevented when alfentanil, and, presumably, other opiates, are used in the anesthetic management of patients with ICP problems.","[{'text': 'alfentanil', 'type': 'Chemical', 'start': 39, 'end': 49, 'mesh': 'D015760'}, {'text': 'rigidity', 'type': 'Disease', 'start': 58, 'end': 66, 'mesh': 'D009127'}, {'text': 'alfentanil', 'type': 'Chemical', 'start': 116, 'end': 126, 'mesh': 'D015760'}, {'text': 'rigidity', 'type': 'Disease', 'start': 135, 'end': 143, 'mesh': 'D009127'}, {'text': 'halothane', 'type': 'Chemical', 'start': 235, 'end': 244, 'mesh': 'D006221'}, {'text': 'halothane', 'type': 'Chemical', 'start': 385, 'end': 394, 'mesh': 'D006221'}, {'text': 'alfentanil', 'type': 'Chemical', 'start': 416, 'end': 426, 'mesh': 'D015760'}, {'text': 'halothane', 'type': 'Chemical', 'start': 477, 'end': 486, 'mesh': 'D006221'}, {'text': 'somatic rigidity', 'type': 'Disease', 'start': 531, 'end': 547, 'mesh': 'D009127'}, {'text': 'rigidity', 'type': 'Disease', 'start': 700, 'end': 708, 'mesh': 'D009127'}, {'text': 'metocurine', 'type': 'Chemical', 'start': 728, 'end': 738, 'mesh': 'C032943'}, {'text': 'alfentanil', 'type': 'Chemical', 'start': 817, 'end': 827, 'mesh': 'D015760'}, {'text': 'rigidity', 'type': 'Disease', 'start': 861, 'end': 869, 'mesh': 'D009127'}, {'text': 'alfentanil', 'type': 'Chemical', 'start': 895, 'end': 905, 'mesh': 'D015760'}]"
+190,3187073,Adverse cardiac effects during induction chemotherapy treatment with cis-platin and 5-fluorouracil.,"Survival for patients with advanced head and neck carcinoma and esophageal carcinoma is poor with radiotherapy and/or surgery. Obviously, there is a need for effective chemotherapy. In the present study, cis-platin (80-120 mg/m2BSA) and 5-FU (1000 mg/m2BSA daily as a continuous infusion during 5 days) were given to 76 patients before radiotherapy and surgery. The aim of the study was to clarify the incidence and severity of adverse cardiac effects to this treatment. Before treatment all patients had a cardiac evaluation and during treatment serial ECG recordings were performed. In the pre-treatment evaluation, signs of cardiovascular disease were found in 33 patients (43%). During treatment, adverse cardiac effects were observed in 14 patients (18%). The mean age of these patients was the same as for the entire group, 64 years. The incidence of cardiotoxicity was not higher in patients with signs of cardiovascular disease than in those without in the pre-treatment evaluation. The most common signs of cardiotoxicity were chest pain, ST-T wave changes and atrial fibrillation. This was followed by ventricular fibrillation in one patient and sudden death in another. It is concluded that patients on 5-FU treatment should be under close supervision and that the treatment should be discontinued if chest pain or tachyarrhythmia is observed.","[{'text': 'cis-platin', 'type': 'Chemical', 'start': 69, 'end': 79, 'mesh': 'D002945'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 84, 'end': 98, 'mesh': 'D005472'}, {'text': 'head and neck carcinoma', 'type': 'Disease', 'start': 136, 'end': 159, 'mesh': 'D006258'}, {'text': 'esophageal carcinoma', 'type': 'Disease', 'start': 164, 'end': 184, 'mesh': 'D004938'}, {'text': 'cis-platin', 'type': 'Chemical', 'start': 304, 'end': 314, 'mesh': 'D002945'}, {'text': '5-FU', 'type': 'Chemical', 'start': 337, 'end': 341, 'mesh': 'D005472'}, {'text': 'cardiovascular disease', 'type': 'Disease', 'start': 727, 'end': 749, 'mesh': 'D002318'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 957, 'end': 971, 'mesh': 'D066126'}, {'text': 'cardiovascular disease', 'type': 'Disease', 'start': 1013, 'end': 1035, 'mesh': 'D002318'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1116, 'end': 1130, 'mesh': 'D066126'}, {'text': 'chest pain', 'type': 'Disease', 'start': 1136, 'end': 1146, 'mesh': 'D002637'}, {'text': 'atrial fibrillation', 'type': 'Disease', 'start': 1170, 'end': 1189, 'mesh': 'D001281'}, {'text': 'ventricular fibrillation', 'type': 'Disease', 'start': 1212, 'end': 1236, 'mesh': 'D014693'}, {'text': 'sudden death', 'type': 'Disease', 'start': 1256, 'end': 1268, 'mesh': 'D003645'}, {'text': '5-FU', 'type': 'Chemical', 'start': 1314, 'end': 1318, 'mesh': 'D005472'}, {'text': 'chest pain', 'type': 'Disease', 'start': 1412, 'end': 1422, 'mesh': 'D002637'}, {'text': 'tachyarrhythmia', 'type': 'Disease', 'start': 1426, 'end': 1441, 'mesh': 'D013610'}]"
+191,3371379,Verapamil-induced carbamazepine neurotoxicity. A report of two cases.,Two patients with signs of carbamazepine neurotoxicity after combined treatment with verapamil showed complete recovery after discontinuation of the calcium entry blocker. Use of verapamil in combination with carbamazepine should either be avoided or prescribed only with appropriate adjustment of the carbamazepine dose (usually reduction of the carbamazepine dose by one half).,"[{'text': 'Verapamil', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D014700'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 18, 'end': 31, 'mesh': 'D002220'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 32, 'end': 45, 'mesh': 'D020258'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 97, 'end': 110, 'mesh': 'D002220'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 111, 'end': 124, 'mesh': 'D020258'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 155, 'end': 164, 'mesh': 'D014700'}, {'text': 'calcium', 'type': 'Chemical', 'start': 219, 'end': 226, 'mesh': 'D002118'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 249, 'end': 258, 'mesh': 'D014700'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 279, 'end': 292, 'mesh': 'D002220'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 372, 'end': 385, 'mesh': 'D002220'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 417, 'end': 430, 'mesh': 'D002220'}]"
+192,3503576,Serial studies of auditory neurotoxicity in patients receiving deferoxamine therapy.,"Visual and auditory neurotoxicity was previously documented in 42 of 89 patients with transfusion-dependent anemia who were receiving iron chelation therapy with daily subcutaneous deferoxamine. Twenty-two patients in the affected group had abnormal audiograms with deficits mostly in the high frequency range of 4,000 to 8,000 Hz and in the hearing threshold levels of 30 to 100 decibels. When deferoxamine therapy was discontinued and serial studies were performed, audiograms in seven cases reverted to normal or near normal within two to three weeks, and nine of 13 patients with symptoms became asymptomatic. Audiograms from 15 patients remained abnormal and four patients required hearing aids because of permanent disability. Since 18 of the 22 patients were initially receiving deferoxamine doses in excess of the commonly recommended 50 mg/kg per dose, therapy was restarted with lower doses, usually 50 mg/kg per dose or less depending on the degree of auditory abnormality, and with the exception of two cases no further toxicity was demonstrated. Auditory deterioration and improvement, demonstrated serially in individual patients receiving and not receiving deferoxamine, respectively, provided convincing evidence for a cause-and-effect relation between deferoxamine administration and ototoxicity. Based on these data, a plan of management was developed that allows effective yet safe administration of deferoxamine. A dose of 50 mg/kg is recommended in those without audiogram abnormalities. With mild toxicity, a reduction to 30 or 40 mg/kg per dose should result in a reversal of the abnormal results to normal within four weeks. Moderate abnormalities require a reduction of deferoxamine to 25 mg/kg per dose with careful monitoring. In those with symptoms of hearing loss, the drug should be stopped for four weeks, and when the audiogram is stable or improved, therapy should be restarted at 10 to 25 mg/kg per dose. Serial audiograms should be performed every six months in those without problems and more frequently in young patients with normal serum ferritin values and in those with auditory dysfunction.","[{'text': 'auditory neurotoxicity', 'type': 'Disease', 'start': 18, 'end': 40, 'mesh': 'D006311'}, {'text': 'deferoxamine', 'type': 'Chemical', 'start': 63, 'end': 75, 'mesh': 'D003676'}, {'text': 'anemia', 'type': 'Disease', 'start': 193, 'end': 199, 'mesh': 'D000740'}, {'text': 'iron', 'type': 'Chemical', 'start': 219, 'end': 223, 'mesh': 'D007501'}, {'text': 'deferoxamine', 'type': 'Chemical', 'start': 266, 'end': 278, 'mesh': 'D003676'}, {'text': 'abnormal audiograms with deficits mostly in the high frequency range of 4,000 to 8,000 Hz', 'type': 'Disease', 'start': 326, 'end': 415, 'mesh': 'D006316'}, {'text': 'deferoxamine', 'type': 'Chemical', 'start': 480, 'end': 492, 'mesh': 'D003676'}, {'text': 'permanent disability', 'type': 'Disease', 'start': 796, 'end': 816, 'mesh': 'D003638'}, {'text': 'deferoxamine', 'type': 'Chemical', 'start': 871, 'end': 883, 'mesh': 'D003676'}, {'text': 'auditory abnormality', 'type': 'Disease', 'start': 1048, 'end': 1068, 'mesh': 'D006311'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1117, 'end': 1125, 'mesh': 'D064420'}, {'text': 'deferoxamine', 'type': 'Chemical', 'start': 1257, 'end': 1269, 'mesh': 'D003676'}, {'text': 'deferoxamine', 'type': 'Chemical', 'start': 1354, 'end': 1366, 'mesh': 'D003676'}, {'text': 'ototoxicity', 'type': 'Disease', 'start': 1386, 'end': 1397, 'mesh': 'D006311'}, {'text': 'deferoxamine', 'type': 'Chemical', 'start': 1504, 'end': 1516, 'mesh': 'D003676'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1604, 'end': 1612, 'mesh': 'D064420'}, {'text': 'deferoxamine', 'type': 'Chemical', 'start': 1780, 'end': 1792, 'mesh': 'D003676'}, {'text': 'hearing loss', 'type': 'Disease', 'start': 1865, 'end': 1877, 'mesh': 'D034381'}, {'text': 'auditory dysfunction', 'type': 'Disease', 'start': 2195, 'end': 2215, 'mesh': 'D006311'}]"
+193,3560095,Flurbiprofen in the treatment of juvenile rheumatoid arthritis.,"Thirty-four patients with juvenile rheumatoid arthritis, who were treated with flurbiprofen at a maximum dose of 4 mg/kg/day, had statistically significant decreases from baseline in 6 arthritis indices after 12 weeks of treatment. Improvements were seen in the number of tender joints, the severity of swelling and tenderness, the time of walk 50 feet, the duration of morning stiffness and the circumference of the left knee. The most frequently observed side effect was fecal occult blood (25% of patients); however, there was no other evidence of gastrointestinal (GI) bleeding in these patients. One patient was prematurely discontinued from the study for severe headache and abdominal pain. Most side effects were mild and related to the GI tract.","[{'text': 'Flurbiprofen', 'type': 'Chemical', 'start': 0, 'end': 12, 'mesh': 'D005480'}, {'text': 'juvenile rheumatoid arthritis', 'type': 'Disease', 'start': 33, 'end': 62, 'mesh': 'D001171'}, {'text': 'juvenile rheumatoid arthritis', 'type': 'Disease', 'start': 90, 'end': 119, 'mesh': 'D001171'}, {'text': 'flurbiprofen', 'type': 'Chemical', 'start': 143, 'end': 155, 'mesh': 'D005480'}, {'text': 'arthritis', 'type': 'Disease', 'start': 249, 'end': 258, 'mesh': 'D001168'}, {'text': 'tender joints', 'type': 'Disease', 'start': 336, 'end': 349, 'mesh': '-1'}, {'text': 'swelling', 'type': 'Disease', 'start': 367, 'end': 375, 'mesh': 'D004487'}, {'text': 'tenderness', 'type': 'Disease', 'start': 380, 'end': 390, 'mesh': '-1'}, {'text': 'morning stiffness', 'type': 'Disease', 'start': 434, 'end': 451, 'mesh': '-1'}, {'text': 'fecal occult blood', 'type': 'Disease', 'start': 537, 'end': 555, 'mesh': '-1'}, {'text': 'gastrointestinal (GI) bleeding', 'type': 'Disease', 'start': 615, 'end': 645, 'mesh': 'D006471'}, {'text': 'headache', 'type': 'Disease', 'start': 732, 'end': 740, 'mesh': 'D006261'}, {'text': 'abdominal pain', 'type': 'Disease', 'start': 745, 'end': 759, 'mesh': 'D015746'}]"
+194,3714122,The correlation between neurotoxic esterase inhibition and mipafox-induced neuropathic damage in rats.,"The correlation between neuropathic damage and inhibition of neurotoxic esterase or neuropathy target enzyme (NTE) was examined in rats acutely exposed to Mipafox (N, N'-diisopropylphosphorodiamidofluoridate), a neurotoxic organophosphate. Brain and spinal cord NTE activities were measured in Long-Evans male rats 1 hr post-exposure to various dosages of Mipafox (ip, 1-15 mg/kg). These data were correlated with histologically scored cervical cord damage in a separate group of similarly dosed rats sampled 14-21 days post-exposure. Those dosages (greater than or equal to 10 mg/kg) that inhibited mean NTE activity in the spinal cord greater than or equal to 73% and brain greater than or equal to 67% of control values produced severe (greater than or equal to 3) cervical cord pathology in 85% of the rats. In contrast, dosages of Mipafox (less than or equal to 5 mg/kg) which inhibited mean NTE activity in spinal cord less than or equal to 61% and brain less than or equal to 60% produced this degree of cord damage in only 9% of the animals. These data indicate that a critical percentage of NTE inhibition in brain and spinal cord sampled shortly after Mipafox exposure can predict neuropathic damage in rats several weeks later.","[{'text': 'neurotoxic', 'type': 'Disease', 'start': 24, 'end': 34, 'mesh': 'D020258'}, {'text': 'mipafox', 'type': 'Chemical', 'start': 59, 'end': 66, 'mesh': 'C005238'}, {'text': 'neuropathic damage', 'type': 'Disease', 'start': 75, 'end': 93, 'mesh': 'D009422'}, {'text': 'neuropathic damage', 'type': 'Disease', 'start': 127, 'end': 145, 'mesh': 'D009422'}, {'text': 'neurotoxic', 'type': 'Disease', 'start': 164, 'end': 174, 'mesh': 'D020258'}, {'text': 'neuropathy', 'type': 'Disease', 'start': 187, 'end': 197, 'mesh': 'D009422'}, {'text': 'Mipafox', 'type': 'Chemical', 'start': 258, 'end': 265, 'mesh': 'C005238'}, {'text': ""N, N'-diisopropylphosphorodiamidofluoridate"", 'type': 'Chemical', 'start': 267, 'end': 310, 'mesh': 'C005238'}, {'text': 'neurotoxic', 'type': 'Disease', 'start': 315, 'end': 325, 'mesh': 'D020258'}, {'text': 'organophosphate', 'type': 'Chemical', 'start': 326, 'end': 341, 'mesh': 'D010755'}, {'text': 'Mipafox', 'type': 'Chemical', 'start': 459, 'end': 466, 'mesh': 'C005238'}, {'text': 'cord damage', 'type': 'Disease', 'start': 548, 'end': 559, 'mesh': 'D013118'}, {'text': 'Mipafox', 'type': 'Chemical', 'start': 939, 'end': 946, 'mesh': 'C005238'}, {'text': 'cord damage', 'type': 'Disease', 'start': 1114, 'end': 1125, 'mesh': 'D013118'}, {'text': 'Mipafox', 'type': 'Chemical', 'start': 1265, 'end': 1272, 'mesh': 'C005238'}, {'text': 'neuropathic damage', 'type': 'Disease', 'start': 1294, 'end': 1312, 'mesh': 'D009422'}]"
+195,3828020,Cerebral infarction with a single oral dose of phenylpropanolamine.,"Phenylpropanolamine (PPA), a synthetic sympathomimetic that is structurally similar to amphetamine, is available over the counter in anorectics, nasal congestants, and cold preparations. Its prolonged use or overuse has been associated with seizures, intracerebral hemorrhage, neuropsychiatric symptoms, and nonhemorrhagic cerebral infarction. We report the case of a young woman who suffered a cerebral infarction after taking a single oral dose of PPA.","[{'text': 'Cerebral infarction', 'type': 'Disease', 'start': 0, 'end': 19, 'mesh': 'D002544'}, {'text': 'phenylpropanolamine', 'type': 'Chemical', 'start': 47, 'end': 66, 'mesh': 'D010665'}, {'text': 'Phenylpropanolamine', 'type': 'Chemical', 'start': 68, 'end': 87, 'mesh': 'D010665'}, {'text': 'PPA', 'type': 'Chemical', 'start': 89, 'end': 92, 'mesh': 'D010665'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 155, 'end': 166, 'mesh': 'D000661'}, {'text': 'seizures', 'type': 'Disease', 'start': 309, 'end': 317, 'mesh': 'D012640'}, {'text': 'intracerebral hemorrhage', 'type': 'Disease', 'start': 319, 'end': 343, 'mesh': 'D002543'}, {'text': 'neuropsychiatric symptoms', 'type': 'Disease', 'start': 345, 'end': 370, 'mesh': 'D001523'}, {'text': 'cerebral infarction', 'type': 'Disease', 'start': 391, 'end': 410, 'mesh': 'D002544'}, {'text': 'cerebral infarction', 'type': 'Disease', 'start': 463, 'end': 482, 'mesh': 'D002544'}, {'text': 'PPA', 'type': 'Chemical', 'start': 518, 'end': 521, 'mesh': 'D010665'}]"
+196,4812392,Treatment of psoriasis with azathioprine.,Azathioprine treatment benefited 19 (66%) out of 29 patients suffering from severe psoriasis. Haematological complications were not troublesome and results of biochemical liver function tests remained normal. Minimal cholestasis was seen in two cases and portal fibrosis of a reversible degree in eight. Liver biopsies should be undertaken at regular intervals if azathioprine therapy is continued so that structural liver damage may be detected at an early and reversible stage.,"[{'text': 'psoriasis', 'type': 'Disease', 'start': 13, 'end': 22, 'mesh': 'D011565'}, {'text': 'azathioprine', 'type': 'Chemical', 'start': 28, 'end': 40, 'mesh': 'D001379'}, {'text': 'Azathioprine', 'type': 'Chemical', 'start': 42, 'end': 54, 'mesh': 'D001379'}, {'text': 'psoriasis', 'type': 'Disease', 'start': 125, 'end': 134, 'mesh': 'D011565'}, {'text': 'cholestasis', 'type': 'Disease', 'start': 259, 'end': 270, 'mesh': 'D002779'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 304, 'end': 312, 'mesh': 'D005355'}, {'text': 'azathioprine', 'type': 'Chemical', 'start': 406, 'end': 418, 'mesh': 'D001379'}, {'text': 'liver damage', 'type': 'Disease', 'start': 459, 'end': 471, 'mesh': 'D056486'}]"
+197,6518066,Maternal lithium and neonatal Ebstein's anomaly: evaluation with cross-sectional echocardiography.,"Cross-sectional echocardiography was used to evaluate two neonates whose mothers ingested lithium during pregnancy. In one infant, Ebstein's anomaly of the tricuspid valve was identified. In the other infant cross-sectional echocardiography provided reassurance that the infant did not have Ebstein's anomaly. Cross-sectional echocardiographic screening of newborns exposed to lithium during gestation can provide highly accurate, noninvasive assessment of the presence or absence of lithium-induced cardiac malformations.","[{'text': 'lithium', 'type': 'Chemical', 'start': 9, 'end': 16, 'mesh': 'D008094'}, {'text': ""Ebstein's anomaly"", 'type': 'Disease', 'start': 30, 'end': 47, 'mesh': 'D004437'}, {'text': 'lithium', 'type': 'Chemical', 'start': 189, 'end': 196, 'mesh': 'D008094'}, {'text': ""Ebstein's anomaly"", 'type': 'Disease', 'start': 230, 'end': 247, 'mesh': 'D004437'}, {'text': ""Ebstein's anomaly"", 'type': 'Disease', 'start': 390, 'end': 407, 'mesh': 'D004437'}, {'text': 'lithium', 'type': 'Chemical', 'start': 476, 'end': 483, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 583, 'end': 590, 'mesh': 'D008094'}, {'text': 'cardiac malformations', 'type': 'Disease', 'start': 599, 'end': 620, 'mesh': 'D006331'}]"
+198,6534871,Effects of training on the extent of experimental myocardial infarction in aging rats.,"The effects of exercise on the severity of isoproterenol-induced myocardial infarction were studied in female albino rats of 20,40,60 and 80 weeks of age. The rats were trained to swim for a specific duration and for a particular period. The occurrence of infarcts were confirmed by histological methods. Elevations in the serum GOT and GPT were maximum in the sedentary-isoproterenols and minimum in the exercise-controls. These changes in the serum transaminases were associated with corresponding depletions in the cardiac GOT and GPT. However, age was seen to interfere with the responses exhibited by the young and old rats. Studies dealing with myocardial infarction are more informative when dealt with age.","[{'text': 'myocardial infarction', 'type': 'Disease', 'start': 50, 'end': 71, 'mesh': 'D009203'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 130, 'end': 143, 'mesh': 'D007545'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 152, 'end': 173, 'mesh': 'D009203'}, {'text': 'infarcts', 'type': 'Disease', 'start': 343, 'end': 351, 'mesh': 'D007238'}, {'text': 'isoproterenols', 'type': 'Chemical', 'start': 458, 'end': 472, 'mesh': 'D007545'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 738, 'end': 759, 'mesh': 'D009203'}]"
+199,6538499,Effect of polyethylene glycol 400 on adriamycin toxicity in mice.,"The effect of a widely used organic solvent, polyethylene glycol 400 (PEG 400), on the toxic action of an acute or chronic treatment with adriamycin (ADR) was evaluated in mice. PEG 400 impressively decreased both acute high-dose and chronic low-dose-ADR-associated lethality. Light microscopic analysis showed a significant protection against ADR-induced cardiac morphological alterations. Such treatment did not diminish the ADR antitumor activity in L1210 leukemia and in Ehrlich ascites tumor.","[{'text': 'polyethylene glycol 400', 'type': 'Chemical', 'start': 10, 'end': 33, 'mesh': 'D011092'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 37, 'end': 47, 'mesh': 'D004317'}, {'text': 'toxicity', 'type': 'Disease', 'start': 48, 'end': 56, 'mesh': 'D064420'}, {'text': 'polyethylene glycol 400', 'type': 'Chemical', 'start': 111, 'end': 134, 'mesh': 'D011092'}, {'text': 'PEG 400', 'type': 'Chemical', 'start': 136, 'end': 143, 'mesh': 'D011092'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 204, 'end': 214, 'mesh': 'D004317'}, {'text': 'ADR', 'type': 'Chemical', 'start': 216, 'end': 219, 'mesh': 'D004317'}, {'text': 'PEG 400', 'type': 'Chemical', 'start': 244, 'end': 251, 'mesh': 'D011092'}, {'text': 'ADR', 'type': 'Chemical', 'start': 317, 'end': 320, 'mesh': 'D004317'}, {'text': 'ADR', 'type': 'Chemical', 'start': 410, 'end': 413, 'mesh': 'D004317'}, {'text': 'cardiac morphological alterations', 'type': 'Disease', 'start': 422, 'end': 455, 'mesh': 'D009202'}, {'text': 'ADR', 'type': 'Chemical', 'start': 493, 'end': 496, 'mesh': 'D004317'}, {'text': 'L1210 leukemia', 'type': 'Disease', 'start': 519, 'end': 533, 'mesh': 'D007939'}, {'text': 'Ehrlich ascites tumor', 'type': 'Disease', 'start': 541, 'end': 562, 'mesh': 'D002286'}]"
+200,6747681,Intra-arterial BCNU chemotherapy for treatment of malignant gliomas of the central nervous system.,"Because of the rapid systemic clearance of BCNU (1,3-bis-(2-chloroethyl)-1-nitrosourea), intra-arterial administration should provide a substantial advantage over intravenous administration for the treatment of malignant gliomas. Thirty-six patients were treated with BCNU every 6 to 8 weeks, either by transfemoral catheterization of the internal carotid or vertebral artery or through a fully implantable intracarotid drug delivery system, beginning with a dose of 200 mg/sq m body surface area. Twelve patients with Grade III or IV astrocytomas were treated after partial resection of the tumor without prior radiation therapy. After two to seven cycles of chemotherapy, nine patients showed a decrease in tumor size and surrounding edema on contrast-enhanced computerized tomography scans. In the nine responders, median duration of chemotherapy response from the time of operation was 25 weeks (range 12 to more than 91 weeks). The median duration of survival in the 12 patients was 54 weeks (range 21 to more than 156 weeks), with an 18-month survival rate of 42%. Twenty-four patients with recurrent Grade I to IV astrocytomas, whose resection and irradiation therapy had failed, received two to eight courses of intra-arterial BCNU therapy. Seventeen of these had a response or were stable for a median of 20 weeks (range 6 to more than 66 weeks). The catheterization procedure is safe, with no immediate complication in 111 infusions of BCNU. A delayed complication in nine patients has been unilateral loss of vision secondary to a retinal vasculitis. The frequency of visual loss decreased after the concentration of the ethanol diluent was lowered.","[{'text': 'BCNU', 'type': 'Chemical', 'start': 15, 'end': 19, 'mesh': 'D002330'}, {'text': 'malignant gliomas', 'type': 'Disease', 'start': 50, 'end': 67, 'mesh': 'D005910'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 142, 'end': 146, 'mesh': 'D002330'}, {'text': '1,3-bis-(2-chloroethyl)-1-nitrosourea', 'type': 'Chemical', 'start': 148, 'end': 185, 'mesh': 'D002330'}, {'text': 'malignant gliomas', 'type': 'Disease', 'start': 310, 'end': 327, 'mesh': 'D005910'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 367, 'end': 371, 'mesh': 'D002330'}, {'text': 'astrocytomas', 'type': 'Disease', 'start': 634, 'end': 646, 'mesh': 'D001254'}, {'text': 'tumor', 'type': 'Disease', 'start': 691, 'end': 696, 'mesh': 'D009369'}, {'text': 'tumor', 'type': 'Disease', 'start': 808, 'end': 813, 'mesh': 'D009369'}, {'text': 'edema', 'type': 'Disease', 'start': 835, 'end': 840, 'mesh': 'D004487'}, {'text': 'astrocytomas', 'type': 'Disease', 'start': 1220, 'end': 1232, 'mesh': 'D001254'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 1334, 'end': 1338, 'mesh': 'D002330'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 1545, 'end': 1549, 'mesh': 'D002330'}, {'text': 'loss of vision', 'type': 'Disease', 'start': 1611, 'end': 1625, 'mesh': 'D014786'}, {'text': 'retinal vasculitis', 'type': 'Disease', 'start': 1641, 'end': 1659, 'mesh': 'D031300'}, {'text': 'visual loss', 'type': 'Disease', 'start': 1678, 'end': 1689, 'mesh': 'D014786'}, {'text': 'ethanol', 'type': 'Chemical', 'start': 1731, 'end': 1738, 'mesh': 'D000431'}]"
+201,6861444,Blood pressure response to chronic low-dose intrarenal noradrenaline infusion in conscious rats.,"Sodium chloride solution (0.9%) or noradrenaline in doses of 4, 12 and 36 micrograms h-1 kg-1 was infused for five consecutive days, either intrarenally (by a new technique) or intravenously into rats with one kidney removed. Intrarenal infusion of noradrenaline caused hypertension at doses which did not do so when infused intravenously. Intrarenal compared with intravenous infusion of noradrenaline caused higher plasma noradrenaline concentrations and a shift of the plasma noradrenaline concentration-blood pressure effect curve towards lower plasma noradrenaline levels. These results suggest that hypertension after chronic intrarenal noradrenaline infusion is produced by relatively higher levels of circulating noradrenaline and by triggering of an additional intrarenal pressor mechanism.","[{'text': 'noradrenaline', 'type': 'Chemical', 'start': 55, 'end': 68, 'mesh': 'D009638'}, {'text': 'Sodium chloride', 'type': 'Chemical', 'start': 97, 'end': 112, 'mesh': 'D012965'}, {'text': 'noradrenaline', 'type': 'Chemical', 'start': 132, 'end': 145, 'mesh': 'D009638'}, {'text': 'noradrenaline', 'type': 'Chemical', 'start': 346, 'end': 359, 'mesh': 'D009638'}, {'text': 'hypertension', 'type': 'Disease', 'start': 367, 'end': 379, 'mesh': 'D006973'}, {'text': 'noradrenaline', 'type': 'Chemical', 'start': 486, 'end': 499, 'mesh': 'D009638'}, {'text': 'noradrenaline', 'type': 'Chemical', 'start': 521, 'end': 534, 'mesh': 'D009638'}, {'text': 'noradrenaline', 'type': 'Chemical', 'start': 576, 'end': 589, 'mesh': 'D009638'}, {'text': 'noradrenaline', 'type': 'Chemical', 'start': 653, 'end': 666, 'mesh': 'D009638'}, {'text': 'hypertension', 'type': 'Disease', 'start': 702, 'end': 714, 'mesh': 'D006973'}, {'text': 'noradrenaline', 'type': 'Chemical', 'start': 740, 'end': 753, 'mesh': 'D009638'}, {'text': 'noradrenaline', 'type': 'Chemical', 'start': 818, 'end': 831, 'mesh': 'D009638'}]"
+202,7053303,Age and renal clearance of cimetidine.,"In 35 patients (ages 20 to 86 yr) receiving cimetidine therapeutically two serum samples and all urine formed in the interim were collected for analysis of cimetidine by high-pressure liquid chromatography and for creatinine. Cimetidine clearance decreased with age. The extrapolated 6-hr serum concentration of cimetidine per unit dose, after intravenous cimetidine, increased with age of the patients. The ratio of cimetidine clearance to creatinine clearance (Rc) averaged 4.8 +/- 2.0, indicating net tubular secretion for cimetidine. Rc seemed to be independent of age and decreased with increasing serum concentration of cimetidine, suggesting that secretion of cimetidine is a saturable process. There was only one case of dementia possibly due to cimetidine (with a drug level of 1.9 microgram/ml 6 hr after a dose) in a group of 13 patients without liver or kidney disease who had cimetidine levels above 1.25 microgram/ml. Thus, high cimetidine levels alone do not always induce dementia.","[{'text': 'cimetidine', 'type': 'Chemical', 'start': 27, 'end': 37, 'mesh': 'D002927'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 83, 'end': 93, 'mesh': 'D002927'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 195, 'end': 205, 'mesh': 'D002927'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 253, 'end': 263, 'mesh': 'D003404'}, {'text': 'Cimetidine', 'type': 'Chemical', 'start': 265, 'end': 275, 'mesh': 'D002927'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 351, 'end': 361, 'mesh': 'D002927'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 395, 'end': 405, 'mesh': 'D002927'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 456, 'end': 466, 'mesh': 'D002927'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 480, 'end': 490, 'mesh': 'D003404'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 565, 'end': 575, 'mesh': 'D002927'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 665, 'end': 675, 'mesh': 'D002927'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 706, 'end': 716, 'mesh': 'D002927'}, {'text': 'dementia', 'type': 'Disease', 'start': 768, 'end': 776, 'mesh': 'D003704'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 793, 'end': 803, 'mesh': 'D002927'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 928, 'end': 938, 'mesh': 'D002927'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 982, 'end': 992, 'mesh': 'D002927'}, {'text': 'dementia', 'type': 'Disease', 'start': 1027, 'end': 1035, 'mesh': 'D003704'}]"
+203,7088431,Development of clear cell adenocarcinoma in DES-exposed offspring under observation.,"Two cases of clear cell adenocarcinoma of the vagina detected at follow-up in young women exposed in utero to diethylstilbestrol are reported. One patient, aged 23, had been followed for 2 years before carcinoma was diagnosed; the second patient, aged 22, had been seen on a regular basis for 5 years, 8 months. In both instances, suspicion of the presence of carcinoma was aroused by the palpation of a small nodule in the vaginal fornix. Hysterosalpingography was performed on both patients and, in 1 instance, an abnormal x-ray film was reflected by the gross appearance of the uterine cavity found in the surgical specimen.","[{'text': 'clear cell adenocarcinoma', 'type': 'Disease', 'start': 15, 'end': 40, 'mesh': 'D018262'}, {'text': 'DES', 'type': 'Chemical', 'start': 44, 'end': 47, 'mesh': 'D004054'}, {'text': 'diethylstilbestrol', 'type': 'Chemical', 'start': 195, 'end': 213, 'mesh': 'D004054'}, {'text': 'carcinoma', 'type': 'Disease', 'start': 287, 'end': 296, 'mesh': 'D002277'}, {'text': 'carcinoma', 'type': 'Disease', 'start': 445, 'end': 454, 'mesh': 'D002277'}]"
+204,7248170,Phenobarbitone-induced enlargement of the liver in the rat: its relationship to carbon tetrachloride-induced cirrhosis.,"The yield of severe cirrhosis of the liver (defined as a shrunken finely nodular liver with micronodular histology, ascites greater than 30 ml, plasma albumin less than 2.2 g/dl, splenomegaly 2-3 times normal, and testicular atrophy approximately half normal weight) after 12 doses of carbon tetrachloride given intragastrically in the phenobarbitone-primed rat was increased from 25% to 56% by giving the initial ""calibrating"" dose of carbon tetrachloride at the peak of the phenobarbitone-induced enlargement of the liver. At this point it was assumed that the cytochrome P450/CCl4 toxic state was both maximal and stable. The optimal rat size to begin phenobarbitone was determined as 100 g, and this size as a group had a mean maximum relative liver weight increase 47% greater than normal rats of the same body weight. The optimal time for the initial dose of carbon tetrachloride was after 14 days on phenobarbitone.","[{'text': 'Phenobarbitone', 'type': 'Chemical', 'start': 0, 'end': 14, 'mesh': 'D010634'}, {'text': 'enlargement of the liver', 'type': 'Disease', 'start': 23, 'end': 47, 'mesh': 'D006529'}, {'text': 'carbon tetrachloride', 'type': 'Chemical', 'start': 80, 'end': 100, 'mesh': 'D002251'}, {'text': 'cirrhosis', 'type': 'Disease', 'start': 109, 'end': 118, 'mesh': 'D005355'}, {'text': 'cirrhosis of the liver', 'type': 'Disease', 'start': 140, 'end': 162, 'mesh': 'D008103'}, {'text': 'ascites', 'type': 'Disease', 'start': 236, 'end': 243, 'mesh': 'D001201'}, {'text': 'splenomegaly', 'type': 'Disease', 'start': 299, 'end': 311, 'mesh': 'D013163'}, {'text': 'atrophy', 'type': 'Disease', 'start': 345, 'end': 352, 'mesh': 'D001284'}, {'text': 'carbon tetrachloride', 'type': 'Chemical', 'start': 405, 'end': 425, 'mesh': 'D002251'}, {'text': 'phenobarbitone', 'type': 'Chemical', 'start': 456, 'end': 470, 'mesh': 'D010634'}, {'text': 'carbon tetrachloride', 'type': 'Chemical', 'start': 556, 'end': 576, 'mesh': 'D002251'}, {'text': 'phenobarbitone', 'type': 'Chemical', 'start': 596, 'end': 610, 'mesh': 'D010634'}, {'text': 'enlargement of the liver', 'type': 'Disease', 'start': 619, 'end': 643, 'mesh': 'D006529'}, {'text': 'CCl4', 'type': 'Chemical', 'start': 699, 'end': 703, 'mesh': 'D002251'}, {'text': 'phenobarbitone', 'type': 'Chemical', 'start': 775, 'end': 789, 'mesh': 'D010634'}, {'text': 'carbon tetrachloride', 'type': 'Chemical', 'start': 985, 'end': 1005, 'mesh': 'D002251'}, {'text': 'phenobarbitone', 'type': 'Chemical', 'start': 1027, 'end': 1041, 'mesh': 'D010634'}]"
+205,7453952,Attenuation of the lithium-induced diabetes-insipidus-like syndrome by amiloride in rats.,"The effect of amiloride on lithium-induced polydipsia and polyuria and on the lithium concentration in the plasma, brain, kidney, thyroid and red blood cells was investigated in rats, chronically treated with LiCl. Amiloride reduced the drinking and urine volume of rats in an acute (6 or 12 h) and a subacute (3 days) experiment. 6 h after the administration of amiloride, a reduction was observed in the lithium content of the renal medulla but not in the other organs studied. At 12 h, all the tissues showed a slight increase in lithium levels. After 3 days of combined treatment, a marked elevation in plasma and tissue lithium levels accompanied a reduction in water intake. In all the experiments, the attenuation of the lithium-induced diabetes-insipidus-like syndrome by amiloride was accompanied by a reduction of the ratio between the lithium concentration in the renal medulla and its levels in the blood and an elevation in the plasma potassium level. It is concluded that acute amiloride administration to lithium-treated patients suffering from polydipsia and polyuria might relieve these patients but prolonged amiloride supplementation would result in elevated lithium levels and might be hazardous.","[{'text': 'lithium', 'type': 'Chemical', 'start': 19, 'end': 26, 'mesh': 'D008094'}, {'text': 'diabetes-insipidus-like syndrome', 'type': 'Disease', 'start': 35, 'end': 67, 'mesh': 'D003919'}, {'text': 'amiloride', 'type': 'Chemical', 'start': 71, 'end': 80, 'mesh': 'D000584'}, {'text': 'amiloride', 'type': 'Chemical', 'start': 104, 'end': 113, 'mesh': 'D000584'}, {'text': 'lithium', 'type': 'Chemical', 'start': 117, 'end': 124, 'mesh': 'D008094'}, {'text': 'polydipsia', 'type': 'Disease', 'start': 133, 'end': 143, 'mesh': 'D059606'}, {'text': 'polyuria', 'type': 'Disease', 'start': 148, 'end': 156, 'mesh': 'D011141'}, {'text': 'lithium', 'type': 'Chemical', 'start': 168, 'end': 175, 'mesh': 'D008094'}, {'text': 'LiCl', 'type': 'Chemical', 'start': 299, 'end': 303, 'mesh': 'D018021'}, {'text': 'Amiloride', 'type': 'Chemical', 'start': 305, 'end': 314, 'mesh': 'D000584'}, {'text': 'amiloride', 'type': 'Chemical', 'start': 453, 'end': 462, 'mesh': 'D000584'}, {'text': 'lithium', 'type': 'Chemical', 'start': 496, 'end': 503, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 623, 'end': 630, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 715, 'end': 722, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 818, 'end': 825, 'mesh': 'D008094'}, {'text': 'diabetes-insipidus-like syndrome', 'type': 'Disease', 'start': 834, 'end': 866, 'mesh': 'D003919'}, {'text': 'amiloride', 'type': 'Chemical', 'start': 870, 'end': 879, 'mesh': 'D000584'}, {'text': 'lithium', 'type': 'Chemical', 'start': 936, 'end': 943, 'mesh': 'D008094'}, {'text': 'potassium', 'type': 'Chemical', 'start': 1038, 'end': 1047, 'mesh': 'D011188'}, {'text': 'amiloride', 'type': 'Chemical', 'start': 1082, 'end': 1091, 'mesh': 'D000584'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1110, 'end': 1117, 'mesh': 'D008094'}, {'text': 'polydipsia', 'type': 'Disease', 'start': 1150, 'end': 1160, 'mesh': 'D059606'}, {'text': 'polyuria', 'type': 'Disease', 'start': 1165, 'end': 1173, 'mesh': 'D011141'}, {'text': 'amiloride', 'type': 'Chemical', 'start': 1217, 'end': 1226, 'mesh': 'D000584'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1268, 'end': 1275, 'mesh': 'D008094'}]"
+206,7802851,Safety and side-effects of alprazolam. Controlled study in agoraphobia with panic disorder.,"BACKGROUND: The widespread use of benzodiazepines has led to increasing recognition of their unwanted effects. The efficacy of alprazolam and placebo in panic disorder with agoraphobia, and the side-effect and adverse effect profiles of both drug groups were measured. METHOD: In London and Toronto 154 patients who met DSM-III criteria for panic disorder with agoraphobia were randomised to alprazolam or placebo. Subjects in each drug group also received either exposure or relaxation. Treatment was from weeks 0 to 8 and was then tapered from weeks 8 to 16. RESULTS: Mean alprazolam dose was 5 mg daily. Compared with placebo subjects, alprazolam patients developed more adverse reactions (21% v. 0%) of depression, enuresis, disinhibition and aggression; and more side-effects, particularly sedation, irritability, impaired memory, weight loss and ataxia. Side-effects tended to diminish during treatment but remained significant at week 8. Despite this, the drop-out rate was low. CONCLUSIONS: Alprazolam caused side-effects and adverse effects during treatment but many patients were willing to accept these.","[{'text': 'alprazolam', 'type': 'Chemical', 'start': 27, 'end': 37, 'mesh': 'D000525'}, {'text': 'agoraphobia', 'type': 'Disease', 'start': 59, 'end': 70, 'mesh': 'D000379'}, {'text': 'panic disorder', 'type': 'Disease', 'start': 76, 'end': 90, 'mesh': 'D016584'}, {'text': 'benzodiazepines', 'type': 'Chemical', 'start': 126, 'end': 141, 'mesh': 'D001569'}, {'text': 'alprazolam', 'type': 'Chemical', 'start': 219, 'end': 229, 'mesh': 'D000525'}, {'text': 'panic disorder', 'type': 'Disease', 'start': 245, 'end': 259, 'mesh': 'D016584'}, {'text': 'agoraphobia', 'type': 'Disease', 'start': 265, 'end': 276, 'mesh': 'D000379'}, {'text': 'panic disorder', 'type': 'Disease', 'start': 433, 'end': 447, 'mesh': 'D016584'}, {'text': 'agoraphobia', 'type': 'Disease', 'start': 453, 'end': 464, 'mesh': 'D000379'}, {'text': 'alprazolam', 'type': 'Chemical', 'start': 484, 'end': 494, 'mesh': 'D000525'}, {'text': 'alprazolam', 'type': 'Chemical', 'start': 667, 'end': 677, 'mesh': 'D000525'}, {'text': 'alprazolam', 'type': 'Chemical', 'start': 731, 'end': 741, 'mesh': 'D000525'}, {'text': 'depression', 'type': 'Disease', 'start': 799, 'end': 809, 'mesh': 'D003866'}, {'text': 'enuresis', 'type': 'Disease', 'start': 811, 'end': 819, 'mesh': 'D004775'}, {'text': 'aggression', 'type': 'Disease', 'start': 839, 'end': 849, 'mesh': 'D001523'}, {'text': 'irritability', 'type': 'Disease', 'start': 897, 'end': 909, 'mesh': 'D001523'}, {'text': 'impaired memory', 'type': 'Disease', 'start': 911, 'end': 926, 'mesh': 'D008569'}, {'text': 'weight loss', 'type': 'Disease', 'start': 928, 'end': 939, 'mesh': 'D015431'}, {'text': 'ataxia', 'type': 'Disease', 'start': 944, 'end': 950, 'mesh': 'D001259'}, {'text': 'Alprazolam', 'type': 'Chemical', 'start': 1091, 'end': 1101, 'mesh': 'D000525'}]"
+207,8319760,Dup 753 prevents the development of puromycin aminonucleoside-induced nephrosis.,"The appearance of nephrotic syndromes such as proteinuria, hypoalbuminemia, hypercholesterolemia and increase in blood nitrogen urea, induced in rats by injection of puromycin aminonucleoside was markedly inhibited by oral administration of Dup 753 (losartan), a novel angiotensin II receptor antagonist, at a dose of 1 or 2 mg/kg per day. The results suggest a possible involvement of the renin-angiotensin system in the development of puromycin aminonucleoside-induced nephrosis.","[{'text': 'Dup 753', 'type': 'Chemical', 'start': 0, 'end': 7, 'mesh': 'D019808'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 36, 'end': 61, 'mesh': 'D011692'}, {'text': 'nephrosis', 'type': 'Disease', 'start': 70, 'end': 79, 'mesh': 'D009401'}, {'text': 'nephrotic syndromes', 'type': 'Disease', 'start': 99, 'end': 118, 'mesh': 'D009404'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 127, 'end': 138, 'mesh': 'D011507'}, {'text': 'hypoalbuminemia', 'type': 'Disease', 'start': 140, 'end': 155, 'mesh': 'D034141'}, {'text': 'hypercholesterolemia', 'type': 'Disease', 'start': 157, 'end': 177, 'mesh': 'D006937'}, {'text': 'blood nitrogen urea', 'type': 'Chemical', 'start': 194, 'end': 213, 'mesh': 'D001806'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 247, 'end': 272, 'mesh': 'D011692'}, {'text': 'Dup 753', 'type': 'Chemical', 'start': 322, 'end': 329, 'mesh': 'D019808'}, {'text': 'losartan', 'type': 'Chemical', 'start': 331, 'end': 339, 'mesh': 'D019808'}, {'text': 'angiotensin II', 'type': 'Chemical', 'start': 350, 'end': 364, 'mesh': 'D000804'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 477, 'end': 488, 'mesh': 'D000809'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 518, 'end': 543, 'mesh': 'D011692'}, {'text': 'nephrosis', 'type': 'Disease', 'start': 552, 'end': 561, 'mesh': 'D009401'}]"
+208,8386779,Sodium bicarbonate alleviates penile pain induced by intracavernous injections for erectile dysfunction.,"In an attempt to determine whether penile pain associated with intracorporeal injections could be due to the acidity of the medication, we performed a randomized study comparing the incidence of penile pain following intracorporeal injections with or without the addition of sodium bicarbonate to the intracorporeal medications. A total of 38 consecutive patients who presented to our clinic with impotence received 0.2 ml. of a combination of 3 drugs: 6 mg. papaverine, 100 micrograms. phentolamine and 10 micrograms. prostaglandin E1 with (pH 7.05) or without (pH 4.17) the addition of sodium bicarbonate (0.03 mEq.). Of the 19 patients without sodium bicarbonate added to the medication 11 (58%) complained of penile pain due to the medication, while only 1 of the 19 men (5%) who received sodium bicarbonate complained of penile pain. From these data we conclude that the penile pain following intracorporeal injections is most likely due to the acidity of the medication, which can be overcome by elevating the pH to a neutral level.","[{'text': 'Sodium bicarbonate', 'type': 'Chemical', 'start': 0, 'end': 18, 'mesh': 'D017693'}, {'text': 'penile pain', 'type': 'Disease', 'start': 30, 'end': 41, 'mesh': 'D004414'}, {'text': 'erectile dysfunction', 'type': 'Disease', 'start': 83, 'end': 103, 'mesh': 'D007172'}, {'text': 'penile pain', 'type': 'Disease', 'start': 140, 'end': 151, 'mesh': 'D004414'}, {'text': 'penile pain', 'type': 'Disease', 'start': 300, 'end': 311, 'mesh': 'D004414'}, {'text': 'sodium bicarbonate', 'type': 'Chemical', 'start': 380, 'end': 398, 'mesh': 'D017693'}, {'text': 'impotence', 'type': 'Disease', 'start': 502, 'end': 511, 'mesh': 'D007172'}, {'text': 'papaverine', 'type': 'Chemical', 'start': 564, 'end': 574, 'mesh': 'D010208'}, {'text': 'phentolamine', 'type': 'Chemical', 'start': 592, 'end': 604, 'mesh': 'D010646'}, {'text': 'prostaglandin E1', 'type': 'Chemical', 'start': 624, 'end': 640, 'mesh': 'D000527'}, {'text': 'sodium bicarbonate', 'type': 'Chemical', 'start': 693, 'end': 711, 'mesh': 'D017693'}, {'text': 'sodium bicarbonate', 'type': 'Chemical', 'start': 752, 'end': 770, 'mesh': 'D017693'}, {'text': 'penile pain', 'type': 'Disease', 'start': 818, 'end': 829, 'mesh': 'D004414'}, {'text': 'sodium bicarbonate', 'type': 'Chemical', 'start': 898, 'end': 916, 'mesh': 'D017693'}, {'text': 'penile pain', 'type': 'Disease', 'start': 931, 'end': 942, 'mesh': 'D004414'}, {'text': 'penile pain', 'type': 'Disease', 'start': 981, 'end': 992, 'mesh': 'D004414'}]"
+209,8421099,Prospective study of the long-term effects of somatostatin analog (octreotide) on gallbladder function and gallstone formation in Chinese acromegalic patients.,"This article reports the changes in gallbladder function examined by ultrasonography in 20 Chinese patients with active acromegaly treated with sc injection of the somatostatin analog octreotide in dosages of 300-1500 micrograms/day for a mean of 24.2 +/- 13.9 months. During treatment with octreotide, 17 patients developed sludge, 10 had gallstones, and 1 developed acute cholecystitis requiring surgery. In all of 7 patients examined acutely, gallbladder contractility was inhibited after a single 100-micrograms injection. In 8 patients followed for 24 weeks, gallbladder contractility remained depressed throughout therapy. After withdrawal of octreotide in 10 patients without gallstones, 8 patients assessed had return of normal gallbladder contractility within 1 month. In 8 of the remaining 10 patients who developed gallstones during treatment, gallbladder contractility normalized in 5 patients (3 of whom has disappearance of their stones within 3 weeks), and remained depressed in 3 (2 of whom had stones present at 6 months). Our results suggest that the suppression of gallbladder contractility is the cause of the successive formation of bile sludge, gallstones, and cholecystitis during octreotide therapy in Chinese acromegalic patients. It is therefore very important to follow the changes of gallbladder function during long-term octreotide therapy of acromegalic patients.","[{'text': 'octreotide', 'type': 'Chemical', 'start': 67, 'end': 77, 'mesh': 'D015282'}, {'text': 'gallstone', 'type': 'Disease', 'start': 107, 'end': 116, 'mesh': 'D042882'}, {'text': 'acromegalic', 'type': 'Disease', 'start': 138, 'end': 149, 'mesh': 'D000172'}, {'text': 'acromegaly', 'type': 'Disease', 'start': 280, 'end': 290, 'mesh': 'D000172'}, {'text': 'octreotide', 'type': 'Chemical', 'start': 344, 'end': 354, 'mesh': 'D015282'}, {'text': 'octreotide', 'type': 'Chemical', 'start': 451, 'end': 461, 'mesh': 'D015282'}, {'text': 'gallstones', 'type': 'Disease', 'start': 500, 'end': 510, 'mesh': 'D042882'}, {'text': 'acute cholecystitis', 'type': 'Disease', 'start': 528, 'end': 547, 'mesh': 'D041881'}, {'text': 'depressed', 'type': 'Disease', 'start': 759, 'end': 768, 'mesh': 'D003866'}, {'text': 'octreotide', 'type': 'Chemical', 'start': 809, 'end': 819, 'mesh': 'D015282'}, {'text': 'gallstones', 'type': 'Disease', 'start': 843, 'end': 853, 'mesh': 'D042882'}, {'text': 'gallstones', 'type': 'Disease', 'start': 986, 'end': 996, 'mesh': 'D042882'}, {'text': 'depressed', 'type': 'Disease', 'start': 1141, 'end': 1150, 'mesh': 'D003866'}, {'text': 'gallstones', 'type': 'Disease', 'start': 1327, 'end': 1337, 'mesh': 'D042882'}, {'text': 'cholecystitis', 'type': 'Disease', 'start': 1343, 'end': 1356, 'mesh': 'D002764'}, {'text': 'octreotide', 'type': 'Chemical', 'start': 1364, 'end': 1374, 'mesh': 'D015282'}, {'text': 'acromegalic', 'type': 'Disease', 'start': 1394, 'end': 1405, 'mesh': 'D000172'}, {'text': 'octreotide', 'type': 'Chemical', 'start': 1510, 'end': 1520, 'mesh': 'D015282'}, {'text': 'acromegalic', 'type': 'Disease', 'start': 1532, 'end': 1543, 'mesh': 'D000172'}]"
+210,8649546,Improvement of levodopa-induced dyskinesia by propranolol in Parkinson's disease.,"Seven patients suffering from Parkinson's disease (PD) with severely disabling dyskinesia received low-dose propranolol as an adjunct to the currently used medical treatment. There was a significant 40% improvement in the dyskinesia score without increase of parkinsonian motor disability. Ballistic and choreic dyskinesia were markedly ameliorated, whereas dystonia was not. This study suggests that administration of low doses of beta-blockers may improve levodopa-induced ballistic and choreic dyskinesia in PD.","[{'text': 'levodopa', 'type': 'Chemical', 'start': 15, 'end': 23, 'mesh': 'D007980'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 32, 'end': 42, 'mesh': 'D004409'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 46, 'end': 57, 'mesh': 'D011433'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 61, 'end': 80, 'mesh': 'D010300'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 112, 'end': 131, 'mesh': 'D010300'}, {'text': 'PD', 'type': 'Disease', 'start': 133, 'end': 135, 'mesh': 'D010300'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 161, 'end': 171, 'mesh': 'D004409'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 190, 'end': 201, 'mesh': 'D011433'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 304, 'end': 314, 'mesh': 'D004409'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 341, 'end': 353, 'mesh': 'D010300'}, {'text': 'motor disability', 'type': 'Disease', 'start': 354, 'end': 370, 'mesh': 'D009069'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 394, 'end': 404, 'mesh': 'D004409'}, {'text': 'dystonia', 'type': 'Disease', 'start': 440, 'end': 448, 'mesh': 'D004421'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 540, 'end': 548, 'mesh': 'D007980'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 579, 'end': 589, 'mesh': 'D004409'}, {'text': 'PD', 'type': 'Disease', 'start': 593, 'end': 595, 'mesh': 'D010300'}]"
+211,8919272,Morphological features of encephalopathy after chronic administration of the antiepileptic drug valproate to rats. A transmission electron microscopic study of capillaries in the cerebellar cortex.,"Long-term intragastric application of the antiepileptic drug sodium valproate (Vupral ""Polfa"") at the effective dose of 200 mg/kg b. w. once daily to rats for 1, 3, 6, 9 and 12 months revealed neurological disorders indicating cerebellum damage (""valproate encephalopathy""). The first ultrastructural changes in structural elements of the blood-brain-barrier (BBB) in the cerebellar cortex were detectable after 3 months of the experiment. They became more severe in the later months of the experiment, and were most severe after 12 months, located mainly in the molecular layer of the cerebellar cortex. Lesions of the capillary included necrosis of endothelial cells. Organelles of these cells, in particular the mitochondria (increased number and size, distinct degeneration of their matrix and cristae) and Golgi apparatus were altered. Reduced size of capillary lumen and occlusion were caused by swollen endothelial cells which had luminal protrusions and swollen microvilli. Pressure on the vessel wall was produced by enlarged perivascular astrocytic processes. Fragments of necrotic endothelial cells were in the vascular lumens and in these there was loosening and breaking of tight cellular junctions. Damage to the vascular basement lamina was also observed. Damage to the capillary was accompanied by marked damage to neuroglial cells, mainly to perivascular processes of astrocytes. The proliferation of astrocytes (Bergmann's in particular) and occasionally of oligodendrocytes was found. Alterations in the structural elements of the BBB coexisted with marked lesions of neurons of the cerebellum (Purkinje cells are earliest). In electron micrographs both luminal and antiluminal sides of the BBB of the cerebellar cortex had similar lesions. The possible influence of the hepatic damage, mainly hyperammonemia, upon the development of valproate encephalopathy is discussed.","[{'text': 'encephalopathy', 'type': 'Disease', 'start': 26, 'end': 40, 'mesh': 'D001927'}, {'text': 'valproate', 'type': 'Chemical', 'start': 96, 'end': 105, 'mesh': 'D014635'}, {'text': 'sodium valproate', 'type': 'Chemical', 'start': 259, 'end': 275, 'mesh': 'D014635'}, {'text': 'neurological disorders', 'type': 'Disease', 'start': 391, 'end': 413, 'mesh': 'D009422'}, {'text': 'cerebellum damage', 'type': 'Disease', 'start': 425, 'end': 442, 'mesh': 'D002526'}, {'text': 'valproate', 'type': 'Chemical', 'start': 445, 'end': 454, 'mesh': 'D014635'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 455, 'end': 469, 'mesh': 'D001927'}, {'text': 'necrosis', 'type': 'Disease', 'start': 837, 'end': 845, 'mesh': 'D009336'}, {'text': 'luminal', 'type': 'Chemical', 'start': 1136, 'end': 1143, 'mesh': 'D010634'}, {'text': 'necrotic', 'type': 'Disease', 'start': 1281, 'end': 1289, 'mesh': 'D009336'}, {'text': 'luminal', 'type': 'Chemical', 'start': 1871, 'end': 1878, 'mesh': 'D010634'}, {'text': 'hepatic damage', 'type': 'Disease', 'start': 1988, 'end': 2002, 'mesh': 'D056486'}, {'text': 'hyperammonemia', 'type': 'Disease', 'start': 2011, 'end': 2025, 'mesh': 'D022124'}, {'text': 'valproate', 'type': 'Chemical', 'start': 2051, 'end': 2060, 'mesh': 'D014635'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 2061, 'end': 2075, 'mesh': 'D001927'}]"
+212,9199746,Macula toxicity after intravitreal amikacin.,"BACKGROUND: Although intravitreal aminoglycosides have substantially improved visual prognosis in endophthalmitis, macular infarction may impair full visual recovery. METHODS: We present a case of presumed amikacin retinal toxicity following treatment with amikacin and vancomycin for alpha-haemolytic streptococcal endophthalmitis. RESULTS: Endophthalmitis resolved with improvement in visual acuity to 6/24 at three months. Fundus fluorescein angiography confirmed macular capillary closure and telangiectasis. CONCLUSIONS: Currently accepted intravitreal antibiotic regimens may cause retinal toxicity and macular ischaemia. Treatment strategies aimed at avoiding retinal toxicity are discussed.","[{'text': 'toxicity', 'type': 'Disease', 'start': 7, 'end': 15, 'mesh': 'D064420'}, {'text': 'amikacin', 'type': 'Chemical', 'start': 35, 'end': 43, 'mesh': 'D000583'}, {'text': 'aminoglycosides', 'type': 'Chemical', 'start': 79, 'end': 94, 'mesh': 'D000617'}, {'text': 'endophthalmitis', 'type': 'Disease', 'start': 143, 'end': 158, 'mesh': 'D009877'}, {'text': 'infarction', 'type': 'Disease', 'start': 168, 'end': 178, 'mesh': 'D007238'}, {'text': 'amikacin', 'type': 'Chemical', 'start': 251, 'end': 259, 'mesh': 'D000583'}, {'text': 'retinal toxicity', 'type': 'Disease', 'start': 260, 'end': 276, 'mesh': 'D012164'}, {'text': 'amikacin', 'type': 'Chemical', 'start': 302, 'end': 310, 'mesh': 'D000583'}, {'text': 'vancomycin', 'type': 'Chemical', 'start': 315, 'end': 325, 'mesh': 'D014640'}, {'text': 'streptococcal endophthalmitis', 'type': 'Disease', 'start': 347, 'end': 376, 'mesh': 'D013290'}, {'text': 'Endophthalmitis', 'type': 'Disease', 'start': 387, 'end': 402, 'mesh': 'D009877'}, {'text': 'fluorescein', 'type': 'Chemical', 'start': 478, 'end': 489, 'mesh': 'D019793'}, {'text': 'telangiectasis', 'type': 'Disease', 'start': 542, 'end': 556, 'mesh': 'D013684'}, {'text': 'retinal toxicity', 'type': 'Disease', 'start': 633, 'end': 649, 'mesh': 'D012164'}, {'text': 'ischaemia', 'type': 'Disease', 'start': 662, 'end': 671, 'mesh': 'D007511'}, {'text': 'retinal toxicity', 'type': 'Disease', 'start': 712, 'end': 728, 'mesh': 'D012164'}]"
+213,9249847,Iatrogenically induced intractable atrioventricular reentrant tachycardia after verapamil and catheter ablation in a patient with Wolff-Parkinson-White syndrome and idiopathic dilated cardiomyopathy.,"In a patient with WPW syndrome and idiopathic dilated cardiomyopathy, intractable atrioventricular reentrant tachycardia (AVRT) was iatrogenically induced. QRS without preexcitation, caused by junctional escape beats after verapamil or unidirectional antegrade block of accessory pathway after catheter ablation, established frequent AVRT attack.","[{'text': 'atrioventricular reentrant tachycardia', 'type': 'Disease', 'start': 35, 'end': 73, 'mesh': 'D013611'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 80, 'end': 89, 'mesh': 'D014700'}, {'text': 'Wolff-Parkinson-White syndrome', 'type': 'Disease', 'start': 130, 'end': 160, 'mesh': 'D014927'}, {'text': 'idiopathic dilated cardiomyopathy', 'type': 'Disease', 'start': 165, 'end': 198, 'mesh': 'D002311'}, {'text': 'WPW syndrome', 'type': 'Disease', 'start': 218, 'end': 230, 'mesh': 'D014927'}, {'text': 'idiopathic dilated cardiomyopathy', 'type': 'Disease', 'start': 235, 'end': 268, 'mesh': 'D002311'}, {'text': 'atrioventricular reentrant tachycardia', 'type': 'Disease', 'start': 282, 'end': 320, 'mesh': 'D013611'}, {'text': 'AVRT', 'type': 'Disease', 'start': 322, 'end': 326, 'mesh': 'D013611'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 423, 'end': 432, 'mesh': 'D014700'}, {'text': 'AVRT', 'type': 'Disease', 'start': 534, 'end': 538, 'mesh': 'D013611'}]"
+214,9284778,Epidemic of liver disease caused by hydrochlorofluorocarbons used as ozone-sparing substitutes of chlorofluorocarbons.,"BACKGROUND: Hydrochlorofluorocarbons (HCFCs) are used increasingly in industry as substitutes for ozone-depleting chlorofluorocarbons (CFCs). Limited studies in animals indicate potential hepatotoxicity of some of these compounds. We investigated an epidemic of liver disease in nine industrial workers who had had repeated accidental exposure to a mixture of 1,1-dichloro-2,2,2-trifluoroethane (HCFC 123) and 1-chloro-1,2,2,2-tetrafluoroethane (HCFC 124). All nine exposed workers were affected to various degrees. Both compounds are metabolised in the same way as 1-bromo-1-chloro-2,2,2-trifluoroethane (halothane) to form reactive trifluoroacetyl halide intermediates, which have been implicated in the hepatotoxicity of halothane. We aimed to test whether HCFCs 123 and 124 can result in serious liver disease. METHODS: For one severely affected worker liver biopsy and immunohistochemical stainings for the presence of trifluoroacetyl protein adducts were done. The serum of six affected workers and five controls was tested for autoantibodies that react with human liver cytochrome-P450 2E1 (P450 2E1) and P58 protein disulphide isomerase isoform (P58). FINDINGS: The liver biopsy sample showed hepatocellular necrosis which was prominent in perivenular zone three and extended focally from portal tracts to portal tracts and centrilobular areas (bridging necrosis). Trifluoroacetyl-adducted proteins were detected in surviving hepatocytes. Autoantibodies against P450 2E1 or P58, previously associated with halothane hepatitis, were detected in the serum of five affected workers. INTERPRETATION: Repeated exposure of human beings to HCFCs 123 and 124 can result in serious liver injury in a large proportion of the exposed population. Although the exact mechanism of hepatotoxicity of these agents is not known, the results suggest that trifluoroacetyl-altered liver proteins are involved. In view of the potentially widespread use of these compounds, there is an urgent need to develop safer alternatives.","[{'text': 'liver disease', 'type': 'Disease', 'start': 12, 'end': 25, 'mesh': 'D008107'}, {'text': 'hydrochlorofluorocarbons', 'type': 'Chemical', 'start': 36, 'end': 60, 'mesh': '-1'}, {'text': 'ozone', 'type': 'Chemical', 'start': 69, 'end': 74, 'mesh': 'D010126'}, {'text': 'chlorofluorocarbons', 'type': 'Chemical', 'start': 98, 'end': 117, 'mesh': 'D017402'}, {'text': 'Hydrochlorofluorocarbons', 'type': 'Chemical', 'start': 131, 'end': 155, 'mesh': '-1'}, {'text': 'HCFCs', 'type': 'Chemical', 'start': 157, 'end': 162, 'mesh': '-1'}, {'text': 'ozone', 'type': 'Chemical', 'start': 217, 'end': 222, 'mesh': 'D010126'}, {'text': 'chlorofluorocarbons', 'type': 'Chemical', 'start': 233, 'end': 252, 'mesh': 'D017402'}, {'text': 'CFCs', 'type': 'Chemical', 'start': 254, 'end': 258, 'mesh': 'D017402'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 307, 'end': 321, 'mesh': 'D056486'}, {'text': 'liver disease', 'type': 'Disease', 'start': 381, 'end': 394, 'mesh': 'D008107'}, {'text': '1,1-dichloro-2,2,2-trifluoroethane', 'type': 'Chemical', 'start': 479, 'end': 513, 'mesh': 'C067411'}, {'text': 'HCFC 123', 'type': 'Chemical', 'start': 515, 'end': 523, 'mesh': 'C067411'}, {'text': '1-chloro-1,2,2,2-tetrafluoroethane', 'type': 'Chemical', 'start': 529, 'end': 563, 'mesh': 'C072959'}, {'text': 'HCFC 124', 'type': 'Chemical', 'start': 565, 'end': 573, 'mesh': 'C072959'}, {'text': '1-bromo-1-chloro-2,2,2-trifluoroethane', 'type': 'Chemical', 'start': 685, 'end': 723, 'mesh': 'D006221'}, {'text': 'halothane', 'type': 'Chemical', 'start': 725, 'end': 734, 'mesh': 'D006221'}, {'text': 'trifluoroacetyl', 'type': 'Chemical', 'start': 753, 'end': 768, 'mesh': 'D014269'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 825, 'end': 839, 'mesh': 'D056486'}, {'text': 'halothane', 'type': 'Chemical', 'start': 843, 'end': 852, 'mesh': 'D006221'}, {'text': 'liver disease', 'type': 'Disease', 'start': 919, 'end': 932, 'mesh': 'D008107'}, {'text': 'trifluoroacetyl', 'type': 'Chemical', 'start': 1043, 'end': 1058, 'mesh': 'D014269'}, {'text': 'necrosis', 'type': 'Disease', 'start': 1335, 'end': 1343, 'mesh': 'D009336'}, {'text': 'necrosis', 'type': 'Disease', 'start': 1481, 'end': 1489, 'mesh': 'D009336'}, {'text': 'Trifluoroacetyl', 'type': 'Chemical', 'start': 1492, 'end': 1507, 'mesh': 'D014269'}, {'text': 'halothane hepatitis', 'type': 'Disease', 'start': 1633, 'end': 1652, 'mesh': 'C562477'}, {'text': 'liver injury', 'type': 'Disease', 'start': 1800, 'end': 1812, 'mesh': 'D056486'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 1894, 'end': 1908, 'mesh': 'D056486'}, {'text': 'trifluoroacetyl', 'type': 'Chemical', 'start': 1964, 'end': 1979, 'mesh': 'D014269'}]"
+215,9522143,The effect of different anaesthetic agents in hearing loss following spinal anaesthesia.,"The cause of hearing loss after spinal anaesthesia is unknown. Up until now, the only factor studied has been the effect of the diameter of the spinal needle on post-operative sensorineural hearing loss. The aim of this study was to describe this hearing loss and to investigate other factors influencing the degree of hearing loss. Two groups of 22 similar patients were studied: one group received 6 mL prilocaine 2%; and the other received 3 mL bupivacaine 0.5%. Patients given prilocaine were more likely to develop hearing loss (10 out of 22) than those given bupivacaine (4 out of 22) (P < 0.05). The average hearing loss for speech frequencies was about 10 dB after prilocaine and 15 dB after bupivacaine. None of the patients complained of subjective hearing loss. Long-term follow-up of the patients was not possible.","[{'text': 'hearing loss', 'type': 'Disease', 'start': 46, 'end': 58, 'mesh': 'D034381'}, {'text': 'hearing loss', 'type': 'Disease', 'start': 102, 'end': 114, 'mesh': 'D034381'}, {'text': 'sensorineural hearing loss', 'type': 'Disease', 'start': 265, 'end': 291, 'mesh': 'D006319'}, {'text': 'hearing loss', 'type': 'Disease', 'start': 336, 'end': 348, 'mesh': 'D034381'}, {'text': 'hearing loss', 'type': 'Disease', 'start': 408, 'end': 420, 'mesh': 'D034381'}, {'text': 'prilocaine', 'type': 'Chemical', 'start': 494, 'end': 504, 'mesh': 'D011318'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 537, 'end': 548, 'mesh': 'D002045'}, {'text': 'prilocaine', 'type': 'Chemical', 'start': 570, 'end': 580, 'mesh': 'D011318'}, {'text': 'hearing loss', 'type': 'Disease', 'start': 609, 'end': 621, 'mesh': 'D034381'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 654, 'end': 665, 'mesh': 'D002045'}, {'text': 'hearing loss', 'type': 'Disease', 'start': 704, 'end': 716, 'mesh': 'D034381'}, {'text': 'prilocaine', 'type': 'Chemical', 'start': 762, 'end': 772, 'mesh': 'D011318'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 789, 'end': 800, 'mesh': 'D002045'}, {'text': 'hearing loss', 'type': 'Disease', 'start': 848, 'end': 860, 'mesh': 'D034381'}]"
+216,9522152,A transient neurological deficit following intrathecal injection of 1% hyperbaric bupivacaine for unilateral spinal anaesthesia.,"We describe a case of transient neurological deficit that occurred after unilateral spinal anaesthesia with 8 mg of 1% hyperbaric bupivacaine slowly injected through a 25-gauge pencil-point spinal needle. The surgery and anaesthesia were uneventful, but 3 days after surgery, the patient reported an area of hypoaesthesia over L3-L4 dermatomes of the leg which had been operated on (loss of pinprick sensation) without reduction in muscular strength. Sensation in this area returned to normal over the following 2 weeks. Prospective multicentre studies with a large population and a long follow-up should be performed in order to evaluate the incidence of this unusual side effect. However, we suggest that a low solution concentration should be preferred for unilateral spinal anaesthesia with a hyperbaric anaesthetic solution (if pencil-point needle and slow injection rate are employed), in order to minimize the risk of a localized high peak anaesthetic concentration, which might lead to a transient neurological deficit.","[{'text': 'neurological deficit', 'type': 'Disease', 'start': 12, 'end': 32, 'mesh': 'D009461'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 82, 'end': 93, 'mesh': 'D002045'}, {'text': 'neurological deficit', 'type': 'Disease', 'start': 161, 'end': 181, 'mesh': 'D009461'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 259, 'end': 270, 'mesh': 'D002045'}, {'text': 'loss of pinprick sensation', 'type': 'Disease', 'start': 512, 'end': 538, 'mesh': 'D012678'}, {'text': 'neurological deficit', 'type': 'Disease', 'start': 1135, 'end': 1155, 'mesh': 'D009461'}]"
+217,9672936,Pethidine-associated seizure in a healthy adolescent receiving pethidine for postoperative pain control.,A healthy 17-year-old male received standard intermittent doses of pethidine via a patient-controlled analgesia (PCA) pump for management of postoperative pain control. Twenty-three h postoperatively he developed a brief self-limited seizure. Both plasma pethidine and norpethidine were elevated in the range associated with clinical manifestations of central nervous system excitation. No other risk factors for CNS toxicity were identified. This method allowed frequent self-dosing of pethidine at short time intervals and rapid accumulation of pethidine and norpethidine. The routine use of pethidine via PCA even for a brief postoperative analgesia should be reconsidered.,"[{'text': 'Pethidine', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D008614'}, {'text': 'seizure', 'type': 'Disease', 'start': 21, 'end': 28, 'mesh': 'D012640'}, {'text': 'pethidine', 'type': 'Chemical', 'start': 63, 'end': 72, 'mesh': 'D008614'}, {'text': 'postoperative pain', 'type': 'Disease', 'start': 77, 'end': 95, 'mesh': 'D010149'}, {'text': 'pethidine', 'type': 'Chemical', 'start': 172, 'end': 181, 'mesh': 'D008614'}, {'text': 'postoperative pain', 'type': 'Disease', 'start': 246, 'end': 264, 'mesh': 'D010149'}, {'text': 'seizure', 'type': 'Disease', 'start': 339, 'end': 346, 'mesh': 'D012640'}, {'text': 'pethidine', 'type': 'Chemical', 'start': 360, 'end': 369, 'mesh': 'D008614'}, {'text': 'norpethidine', 'type': 'Chemical', 'start': 374, 'end': 386, 'mesh': 'C002752'}, {'text': 'toxicity', 'type': 'Disease', 'start': 522, 'end': 530, 'mesh': 'D064420'}, {'text': 'pethidine', 'type': 'Chemical', 'start': 592, 'end': 601, 'mesh': 'D008614'}, {'text': 'pethidine', 'type': 'Chemical', 'start': 652, 'end': 661, 'mesh': 'D008614'}, {'text': 'norpethidine', 'type': 'Chemical', 'start': 666, 'end': 678, 'mesh': 'C002752'}, {'text': 'pethidine', 'type': 'Chemical', 'start': 699, 'end': 708, 'mesh': 'D008614'}]"
+218,9721172,Drug-associated acute-onset vanishing bile duct and Stevens-Johnson syndromes in a child.,"Acute vanishing bile duct syndrome is a rare but established cause of progressive cholestasis in adults, is most often drug or toxin related, and is of unknown pathogenesis. It has not been reported previously in children. Stevens-Johnson syndrome is a well-recognized immune complex-mediated hypersensitivity reaction that affects all age groups, is drug or infection induced, and has classic systemic, mucosal, and dermatologic manifestations. A previously healthy child who developed acute, severe, rapidly progressive vanishing bile duct syndrome shortly after Stevens-Johnson syndrome is described; this was temporally associated with ibuprofen use. Despite therapy with ursodeoxycholic acid, prednisone, and then tacrolimus, her cholestatic disease was unrelenting, with cirrhosis shown by biopsy 6 months after presentation. This case documents acute drug-related vanishing bile duct syndrome in the pediatric age group and suggests shared immune mechanisms in the pathogenesis of both Stevens-Johnson syndrome and vanishing bile duct syndrome.","[{'text': 'vanishing bile duct', 'type': 'Disease', 'start': 28, 'end': 47, 'mesh': 'D001649'}, {'text': 'Stevens-Johnson syndromes', 'type': 'Disease', 'start': 52, 'end': 77, 'mesh': 'D013262'}, {'text': 'vanishing bile duct', 'type': 'Disease', 'start': 96, 'end': 115, 'mesh': 'D001649'}, {'text': 'cholestasis', 'type': 'Disease', 'start': 172, 'end': 183, 'mesh': 'D002779'}, {'text': 'Stevens-Johnson syndrome', 'type': 'Disease', 'start': 313, 'end': 337, 'mesh': 'D013262'}, {'text': 'hypersensitivity', 'type': 'Disease', 'start': 383, 'end': 399, 'mesh': 'D004342'}, {'text': 'infection', 'type': 'Disease', 'start': 449, 'end': 458, 'mesh': 'D007239'}, {'text': 'vanishing bile duct syndrome', 'type': 'Disease', 'start': 612, 'end': 640, 'mesh': 'D001649'}, {'text': 'Stevens-Johnson syndrome', 'type': 'Disease', 'start': 655, 'end': 679, 'mesh': 'D013262'}, {'text': 'ibuprofen', 'type': 'Chemical', 'start': 730, 'end': 739, 'mesh': 'D007052'}, {'text': 'ursodeoxycholic acid', 'type': 'Chemical', 'start': 766, 'end': 786, 'mesh': 'D014580'}, {'text': 'prednisone', 'type': 'Chemical', 'start': 788, 'end': 798, 'mesh': 'D011241'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 809, 'end': 819, 'mesh': 'D016559'}, {'text': 'cholestatic disease', 'type': 'Disease', 'start': 825, 'end': 844, 'mesh': 'D002779'}, {'text': 'cirrhosis', 'type': 'Disease', 'start': 867, 'end': 876, 'mesh': 'D005355'}, {'text': 'vanishing bile duct syndrome', 'type': 'Disease', 'start': 961, 'end': 989, 'mesh': 'D001649'}, {'text': 'Stevens-Johnson syndrome', 'type': 'Disease', 'start': 1083, 'end': 1107, 'mesh': 'D013262'}, {'text': 'vanishing bile duct syndrome', 'type': 'Disease', 'start': 1112, 'end': 1140, 'mesh': 'D001649'}]"
+219,9727773,High incidence of primary pulmonary hypertension associated with appetite suppressants in Belgium.,"Primary pulmonary hypertension is a rare, progressive and incurable disease, which has been associated with the intake of appetite suppressant drugs. The importance of this association was evaluated in Belgium while this country still had no restriction on the prescription of appetite suppressants. Thirty-five patients with primary pulmonary hypertension and 85 matched controls were recruited over 32 months (1992-1994) in Belgium. Exposure to appetite-suppressants was assessed on the basis of hospital records and standardized interview. Twenty-three of the patients had previously taken appetite suppressants, mainly fenfluramines, as compared with only 5 of the controls (66 versus 6%, p<0.0001). Five patients died before the interview, all of them had taken appetite suppressants. In 8 patients the diagnosis of primary pulmonary hypertension was uncertain, 5 of them had taken appetite suppressants. The patients who had been exposed to appetite suppressants tended to be on average more severely ill, and to have a shorter median delay between onset of symptoms and diagnosis. A policy of unrestricted prescription of appetite suppressants may lead to a high incidence of associated primary pulmonary hypertension. Intake of appetite suppressants may accelerate the progression of the disease.","[{'text': 'primary pulmonary hypertension', 'type': 'Disease', 'start': 18, 'end': 48, 'mesh': 'D006976'}, {'text': 'appetite suppressants', 'type': 'Chemical', 'start': 65, 'end': 86, 'mesh': 'D001067'}, {'text': 'Primary pulmonary hypertension', 'type': 'Disease', 'start': 99, 'end': 129, 'mesh': 'D006976'}, {'text': 'appetite suppressant', 'type': 'Chemical', 'start': 221, 'end': 241, 'mesh': 'D001067'}, {'text': 'appetite suppressants', 'type': 'Chemical', 'start': 376, 'end': 397, 'mesh': 'D001067'}, {'text': 'primary pulmonary hypertension', 'type': 'Disease', 'start': 425, 'end': 455, 'mesh': 'D006976'}, {'text': 'appetite-suppressants', 'type': 'Chemical', 'start': 546, 'end': 567, 'mesh': 'D001067'}, {'text': 'appetite suppressants', 'type': 'Chemical', 'start': 692, 'end': 713, 'mesh': 'D001067'}, {'text': 'fenfluramines', 'type': 'Chemical', 'start': 722, 'end': 735, 'mesh': 'D005277'}, {'text': 'appetite suppressants', 'type': 'Chemical', 'start': 866, 'end': 887, 'mesh': 'D001067'}, {'text': 'primary pulmonary hypertension', 'type': 'Disease', 'start': 920, 'end': 950, 'mesh': 'D006976'}, {'text': 'appetite suppressants', 'type': 'Chemical', 'start': 986, 'end': 1007, 'mesh': 'D001067'}, {'text': 'appetite suppressants', 'type': 'Chemical', 'start': 1046, 'end': 1067, 'mesh': 'D001067'}, {'text': 'appetite suppressants', 'type': 'Chemical', 'start': 1228, 'end': 1249, 'mesh': 'D001067'}, {'text': 'primary pulmonary hypertension', 'type': 'Disease', 'start': 1293, 'end': 1323, 'mesh': 'D006976'}, {'text': 'appetite suppressants', 'type': 'Chemical', 'start': 1335, 'end': 1356, 'mesh': 'D001067'}]"
+220,9754849,Choreoathetoid movements associated with rapid adjustment to methadone.,"Choreatiform hyperkinesias are known to be occasional movement abnormalities during intoxications with cocaine but not opiates. This is a case report of euphoria and choreoathetoid movements both transiently induced by rapid adjustment to the selective mu-opioid receptor agonist methadone in an inpatient previously abusing heroine and cocaine. In addition, minor EEG abnormalities occurred. Possible underlying neurobiological phenomena are discussed.","[{'text': 'Choreoathetoid movements', 'type': 'Disease', 'start': 0, 'end': 24, 'mesh': 'D002819'}, {'text': 'methadone', 'type': 'Chemical', 'start': 61, 'end': 70, 'mesh': 'D008691'}, {'text': 'movement abnormalities', 'type': 'Disease', 'start': 126, 'end': 148, 'mesh': 'D020820'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 175, 'end': 182, 'mesh': 'D003042'}, {'text': 'choreoathetoid movements', 'type': 'Disease', 'start': 238, 'end': 262, 'mesh': 'D002819'}, {'text': 'methadone', 'type': 'Chemical', 'start': 352, 'end': 361, 'mesh': 'D008691'}, {'text': 'heroine', 'type': 'Chemical', 'start': 397, 'end': 404, 'mesh': 'D003932'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 409, 'end': 416, 'mesh': 'D003042'}]"
+221,10365197,Cocaine-induced mood disorder: prevalence rates and psychiatric symptoms in an outpatient cocaine-dependent sample.,"This paper attempts to examine and compare prevalence rates and symptom patterns of DSM substance-induced and other mood disorders. 243 cocaine-dependent outpatients with cocaine-induced mood disorder (CIMD), other mood disorders, or no mood disorder were compared on measures of psychiatric symptoms. The prevalence rate for CIMD was 12% at baseline. Introduction of the DSM-IV diagnosis of CIMD did not substantially affect rates of the other depressive disorders. Patients with CIMD had symptom severity levels between those of patients with and without a mood disorder. These findings suggest some validity for the new DSM-IV diagnosis of CIMD, but also suggest that it requires further specification and replication.","[{'text': 'Cocaine', 'type': 'Chemical', 'start': 0, 'end': 7, 'mesh': 'D003042'}, {'text': 'mood disorder', 'type': 'Disease', 'start': 16, 'end': 29, 'mesh': 'D019964'}, {'text': 'psychiatric', 'type': 'Disease', 'start': 52, 'end': 63, 'mesh': 'D001523'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 90, 'end': 97, 'mesh': 'D003042'}, {'text': 'mood disorders', 'type': 'Disease', 'start': 232, 'end': 246, 'mesh': 'D019964'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 252, 'end': 259, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 287, 'end': 294, 'mesh': 'D003042'}, {'text': 'mood disorder', 'type': 'Disease', 'start': 303, 'end': 316, 'mesh': 'D019964'}, {'text': 'CIMD', 'type': 'Disease', 'start': 318, 'end': 322, 'mesh': 'D019970'}, {'text': 'mood disorders', 'type': 'Disease', 'start': 331, 'end': 345, 'mesh': 'D019964'}, {'text': 'mood disorder', 'type': 'Disease', 'start': 353, 'end': 366, 'mesh': 'D019964'}, {'text': 'psychiatric', 'type': 'Disease', 'start': 396, 'end': 407, 'mesh': 'D001523'}, {'text': 'CIMD', 'type': 'Disease', 'start': 442, 'end': 446, 'mesh': 'D019970'}, {'text': 'CIMD', 'type': 'Disease', 'start': 508, 'end': 512, 'mesh': 'D019970'}, {'text': 'depressive disorders', 'type': 'Disease', 'start': 561, 'end': 581, 'mesh': 'D003866'}, {'text': 'CIMD', 'type': 'Disease', 'start': 597, 'end': 601, 'mesh': 'D019970'}, {'text': 'mood disorder', 'type': 'Disease', 'start': 675, 'end': 688, 'mesh': 'D019964'}, {'text': 'CIMD', 'type': 'Disease', 'start': 759, 'end': 763, 'mesh': 'D019970'}]"
+222,10704919,Hemolysis of human erythrocytes induced by tamoxifen is related to disruption of membrane structure.,"Tamoxifen (TAM), the antiestrogenic drug most widely prescribed in the chemotherapy of breast cancer, induces changes in normal discoid shape of erythrocytes and hemolytic anemia. This work evaluates the effects of TAM on isolated human erythrocytes, attempting to identify the underlying mechanisms on TAM-induced hemolytic anemia and the involvement of biomembranes in its cytostatic action mechanisms. TAM induces hemolysis of erythrocytes as a function of concentration. The extension of hemolysis is variable with erythrocyte samples, but 12.5 microM TAM induces total hemolysis of all tested suspensions. Despite inducing extensive erythrocyte lysis, TAM does not shift the osmotic fragility curves of erythrocytes. The hemolytic effect of TAM is prevented by low concentrations of alpha-tocopherol (alpha-T) and alpha-tocopherol acetate (alpha-TAc) (inactivated functional hydroxyl) indicating that TAM-induced hemolysis is not related to oxidative membrane damage. This was further evidenced by absence of oxygen consumption and hemoglobin oxidation both determined in parallel with TAM-induced hemolysis. Furthermore, it was observed that TAM inhibits the peroxidation of human erythrocytes induced by AAPH, thus ruling out TAM-induced cell oxidative stress. Hemolysis caused by TAM was not preceded by the leakage of K(+) from the cells, also excluding a colloid-osmotic type mechanism of hemolysis, according to the effects on osmotic fragility curves. However, TAM induces release of peripheral proteins of membrane-cytoskeleton and cytosol proteins essentially bound to band 3. Either alpha-T or alpha-TAc increases membrane packing and prevents TAM partition into model membranes. These effects suggest that the protection from hemolysis by tocopherols is related to a decreased TAM incorporation in condensed membranes and the structural damage of the erythrocyte membrane is consequently avoided. Therefore, TAM-induced hemolysis results from a structural perturbation of red cell membrane, leading to changes in the framework of the erythrocyte membrane and its cytoskeleton caused by its high partition in the membrane. These defects explain the abnormal erythrocyte shape and decreased mechanical stability promoted by TAM, resulting in hemolytic anemia. Additionally, since membrane leakage is a final stage of cytotoxicity, the disruption of the structural characteristics of biomembranes by TAM may contribute to the multiple mechanisms of its anticancer action.","[{'text': 'Hemolysis', 'type': 'Disease', 'start': 0, 'end': 9, 'mesh': 'D006461'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 43, 'end': 52, 'mesh': 'D013629'}, {'text': 'Tamoxifen', 'type': 'Chemical', 'start': 101, 'end': 110, 'mesh': 'D013629'}, {'text': 'TAM', 'type': 'Chemical', 'start': 112, 'end': 115, 'mesh': 'D013629'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 188, 'end': 201, 'mesh': 'D001943'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 263, 'end': 279, 'mesh': 'D000743'}, {'text': 'TAM', 'type': 'Chemical', 'start': 316, 'end': 319, 'mesh': 'D013629'}, {'text': 'TAM', 'type': 'Chemical', 'start': 404, 'end': 407, 'mesh': 'D013629'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 416, 'end': 432, 'mesh': 'D000743'}, {'text': 'TAM', 'type': 'Chemical', 'start': 506, 'end': 509, 'mesh': 'D013629'}, {'text': 'hemolysis', 'type': 'Disease', 'start': 518, 'end': 527, 'mesh': 'D006461'}, {'text': 'hemolysis', 'type': 'Disease', 'start': 593, 'end': 602, 'mesh': 'D006461'}, {'text': 'TAM', 'type': 'Chemical', 'start': 657, 'end': 660, 'mesh': 'D013629'}, {'text': 'hemolysis', 'type': 'Disease', 'start': 675, 'end': 684, 'mesh': 'D006461'}, {'text': 'TAM', 'type': 'Chemical', 'start': 758, 'end': 761, 'mesh': 'D013629'}, {'text': 'hemolytic', 'type': 'Disease', 'start': 827, 'end': 836, 'mesh': 'D006461'}, {'text': 'TAM', 'type': 'Chemical', 'start': 847, 'end': 850, 'mesh': 'D013629'}, {'text': 'alpha-tocopherol', 'type': 'Chemical', 'start': 889, 'end': 905, 'mesh': 'D024502'}, {'text': 'alpha-T', 'type': 'Chemical', 'start': 907, 'end': 914, 'mesh': 'D024502'}, {'text': 'alpha-tocopherol acetate', 'type': 'Chemical', 'start': 920, 'end': 944, 'mesh': 'D024502'}, {'text': 'alpha-TAc', 'type': 'Chemical', 'start': 946, 'end': 955, 'mesh': 'D024502'}, {'text': 'hydroxyl', 'type': 'Chemical', 'start': 981, 'end': 989, 'mesh': 'D017665'}, {'text': 'TAM', 'type': 'Chemical', 'start': 1007, 'end': 1010, 'mesh': 'D013629'}, {'text': 'hemolysis', 'type': 'Disease', 'start': 1019, 'end': 1028, 'mesh': 'D006461'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 1115, 'end': 1121, 'mesh': 'D010100'}, {'text': 'TAM', 'type': 'Chemical', 'start': 1192, 'end': 1195, 'mesh': 'D013629'}, {'text': 'hemolysis', 'type': 'Disease', 'start': 1204, 'end': 1213, 'mesh': 'D006461'}, {'text': 'TAM', 'type': 'Chemical', 'start': 1249, 'end': 1252, 'mesh': 'D013629'}, {'text': 'AAPH', 'type': 'Chemical', 'start': 1312, 'end': 1316, 'mesh': 'C046728'}, {'text': 'TAM', 'type': 'Chemical', 'start': 1334, 'end': 1337, 'mesh': 'D013629'}, {'text': 'Hemolysis', 'type': 'Disease', 'start': 1369, 'end': 1378, 'mesh': 'D006461'}, {'text': 'TAM', 'type': 'Chemical', 'start': 1389, 'end': 1392, 'mesh': 'D013629'}, {'text': 'K', 'type': 'Chemical', 'start': 1428, 'end': 1429, 'mesh': 'D011188'}, {'text': 'hemolysis', 'type': 'Disease', 'start': 1500, 'end': 1509, 'mesh': 'D006461'}, {'text': 'TAM', 'type': 'Chemical', 'start': 1574, 'end': 1577, 'mesh': 'D013629'}, {'text': 'alpha-T', 'type': 'Chemical', 'start': 1699, 'end': 1706, 'mesh': 'D024502'}, {'text': 'alpha-TAc', 'type': 'Chemical', 'start': 1710, 'end': 1719, 'mesh': 'D024502'}, {'text': 'TAM', 'type': 'Chemical', 'start': 1760, 'end': 1763, 'mesh': 'D013629'}, {'text': 'hemolysis', 'type': 'Disease', 'start': 1843, 'end': 1852, 'mesh': 'D006461'}, {'text': 'tocopherols', 'type': 'Chemical', 'start': 1856, 'end': 1867, 'mesh': 'D024505'}, {'text': 'TAM', 'type': 'Chemical', 'start': 1894, 'end': 1897, 'mesh': 'D013629'}, {'text': 'TAM', 'type': 'Chemical', 'start': 2025, 'end': 2028, 'mesh': 'D013629'}, {'text': 'hemolysis', 'type': 'Disease', 'start': 2037, 'end': 2046, 'mesh': 'D006461'}, {'text': 'TAM', 'type': 'Chemical', 'start': 2339, 'end': 2342, 'mesh': 'D013629'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 2357, 'end': 2373, 'mesh': 'D000743'}, {'text': 'TAM', 'type': 'Chemical', 'start': 2514, 'end': 2517, 'mesh': 'D013629'}]"
+223,10706004,"Changes of sodium and ATP affinities of the cardiac (Na,K)-ATPase during and after nitric oxide deficient hypertension.","In the cardiovascular system, NO is involved in the regulation of a variety of functions. Inhibition of NO synthesis induces sustained hypertension. In several models of hypertension, elevation of intracellular sodium level was documented in cardiac tissue. To assess the molecular basis of disturbances in transmembraneous transport of Na+, we studied the response of cardiac (Na,K)-ATPase to NO-deficient hypertension induced in rats by NO-synthase inhibition with 40 mg/kg/day N(G)-nitro-L-arginine methyl ester (L-NAME) for 4 four weeks. After 4-week administration of L-NAME, the systolic blood pressure (SBP) increased by 36%. Two weeks after terminating the treatment, the SBP recovered to control value. When activating the (Na,K)-ATPase with its substrate ATP, no changes in Km and Vmax values were observed in NO-deficient rats. During activation with Na+, the Vmax remained unchanged, however the K(Na) increased by 50%, indicating a profound decrease in the affinity of the Na+-binding site in NO-deficient rats. After recovery from hypertension, the activity of (Na,K)-ATPase increased, due to higher affinity of the ATP-binding site, as revealed from the lowered Km value for ATP. The K(Na) value for Na+ returned to control value. Inhibition of NO-synthase induced a reversible hypertension accompanied by depressed Na+-extrusion from cardiac cells as a consequence of deteriorated Na+-binding properties of the (Na,K)-ATPase. After recovery of blood pressure to control values, the extrusion of Na+ from cardiac cells was normalized, as revealed by restoration of the (Na,K)-ATPase activity.","[{'text': 'sodium', 'type': 'Chemical', 'start': 11, 'end': 17, 'mesh': 'D012964'}, {'text': 'ATP', 'type': 'Chemical', 'start': 22, 'end': 25, 'mesh': 'D000255'}, {'text': 'Na', 'type': 'Chemical', 'start': 53, 'end': 55, 'mesh': 'D012964'}, {'text': 'K', 'type': 'Chemical', 'start': 56, 'end': 57, 'mesh': 'D011188'}, {'text': 'nitric oxide', 'type': 'Chemical', 'start': 83, 'end': 95, 'mesh': 'D009569'}, {'text': 'hypertension', 'type': 'Disease', 'start': 106, 'end': 118, 'mesh': 'D006973'}, {'text': 'NO', 'type': 'Chemical', 'start': 150, 'end': 152, 'mesh': 'D009569'}, {'text': 'NO', 'type': 'Chemical', 'start': 224, 'end': 226, 'mesh': 'D009569'}, {'text': 'hypertension', 'type': 'Disease', 'start': 255, 'end': 267, 'mesh': 'D006973'}, {'text': 'hypertension', 'type': 'Disease', 'start': 290, 'end': 302, 'mesh': 'D006973'}, {'text': 'sodium', 'type': 'Chemical', 'start': 331, 'end': 337, 'mesh': 'D012964'}, {'text': 'Na', 'type': 'Chemical', 'start': 457, 'end': 459, 'mesh': 'D012964'}, {'text': 'Na', 'type': 'Chemical', 'start': 498, 'end': 500, 'mesh': 'D012964'}, {'text': 'K', 'type': 'Chemical', 'start': 501, 'end': 502, 'mesh': 'D011188'}, {'text': 'NO', 'type': 'Chemical', 'start': 514, 'end': 516, 'mesh': 'D009569'}, {'text': 'hypertension', 'type': 'Disease', 'start': 527, 'end': 539, 'mesh': 'D006973'}, {'text': 'NO', 'type': 'Chemical', 'start': 559, 'end': 561, 'mesh': 'D009569'}, {'text': 'N(G)-nitro-L-arginine methyl ester', 'type': 'Chemical', 'start': 600, 'end': 634, 'mesh': 'D019331'}, {'text': 'L-NAME', 'type': 'Chemical', 'start': 636, 'end': 642, 'mesh': 'D019331'}, {'text': 'L-NAME', 'type': 'Chemical', 'start': 693, 'end': 699, 'mesh': 'D019331'}, {'text': 'Na', 'type': 'Chemical', 'start': 853, 'end': 855, 'mesh': 'D012964'}, {'text': 'K', 'type': 'Chemical', 'start': 856, 'end': 857, 'mesh': 'D011188'}, {'text': 'ATP', 'type': 'Chemical', 'start': 885, 'end': 888, 'mesh': 'D000255'}, {'text': 'NO', 'type': 'Chemical', 'start': 940, 'end': 942, 'mesh': 'D009569'}, {'text': 'Na', 'type': 'Chemical', 'start': 982, 'end': 984, 'mesh': 'D012964'}, {'text': 'K', 'type': 'Chemical', 'start': 1028, 'end': 1029, 'mesh': 'D011188'}, {'text': 'Na', 'type': 'Chemical', 'start': 1030, 'end': 1032, 'mesh': 'D012964'}, {'text': 'Na', 'type': 'Chemical', 'start': 1106, 'end': 1108, 'mesh': 'D012964'}, {'text': 'NO', 'type': 'Chemical', 'start': 1126, 'end': 1128, 'mesh': 'D009569'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1165, 'end': 1177, 'mesh': 'D006973'}, {'text': 'Na', 'type': 'Chemical', 'start': 1196, 'end': 1198, 'mesh': 'D012964'}, {'text': 'K', 'type': 'Chemical', 'start': 1199, 'end': 1200, 'mesh': 'D011188'}, {'text': 'ATP', 'type': 'Chemical', 'start': 1250, 'end': 1253, 'mesh': 'D000255'}, {'text': 'ATP', 'type': 'Chemical', 'start': 1310, 'end': 1313, 'mesh': 'D000255'}, {'text': 'K', 'type': 'Chemical', 'start': 1319, 'end': 1320, 'mesh': 'D011188'}, {'text': 'Na', 'type': 'Chemical', 'start': 1321, 'end': 1323, 'mesh': 'D012964'}, {'text': 'Na', 'type': 'Chemical', 'start': 1335, 'end': 1337, 'mesh': 'D012964'}, {'text': 'NO', 'type': 'Chemical', 'start': 1380, 'end': 1382, 'mesh': 'D009569'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1413, 'end': 1425, 'mesh': 'D006973'}, {'text': 'depressed', 'type': 'Disease', 'start': 1441, 'end': 1450, 'mesh': 'D003866'}, {'text': 'Na', 'type': 'Chemical', 'start': 1451, 'end': 1453, 'mesh': 'D012964'}, {'text': 'Na', 'type': 'Chemical', 'start': 1517, 'end': 1519, 'mesh': 'D012964'}, {'text': 'Na', 'type': 'Chemical', 'start': 1548, 'end': 1550, 'mesh': 'D012964'}, {'text': 'K', 'type': 'Chemical', 'start': 1551, 'end': 1552, 'mesh': 'D011188'}, {'text': 'Na', 'type': 'Chemical', 'start': 1631, 'end': 1633, 'mesh': 'D012964'}, {'text': 'Na', 'type': 'Chemical', 'start': 1705, 'end': 1707, 'mesh': 'D012964'}, {'text': 'K', 'type': 'Chemical', 'start': 1708, 'end': 1709, 'mesh': 'D011188'}]"
+224,10721819,Effects of long-term pretreatment with isoproterenol on bromocriptine-induced tachycardia in conscious rats.,"It has been shown that bromocriptine-induced tachycardia, which persisted after adrenalectomy, is (i) mediated by central dopamine D2 receptor activation and (ii) reduced by 5-day isoproterenol pretreatment, supporting therefore the hypothesis that this effect is dependent on sympathetic outflow to the heart. This study was conducted to examine whether prolonged pretreatment with isoproterenol could abolish bromocriptine-induced tachycardia in conscious rats. Isoproterenol pretreatment for 15 days caused cardiac hypertrophy without affecting baseline blood pressure and heart rate. In control rats, intravenous bromocriptine (150 microg/kg) induced significant hypotension and tachycardia. Bromocriptine-induced hypotension was unaffected by isoproterenol pretreatment, while tachycardia was reversed to significant bradycardia, an effect that was partly reduced by i.v. domperidone (0.5 mg/kg). Neither cardiac vagal nor sympathetic tone was altered by isoproterenol pretreatment. In isolated perfused heart preparations from isoproterenol-pretreated rats, the isoproterenol-induced maximal increase in left ventricular systolic pressure was significantly reduced, compared with saline-pretreated rats (the EC50 of the isoproterenol-induced increase in left ventricular systolic pressure was enhanced approximately 22-fold). These results show that 15-day isoproterenol pretreatment not only abolished but reversed bromocriptine-induced tachycardia to bradycardia, an effect that is mainly related to further cardiac beta-adrenoceptor desensitization rather than to impairment of autonomic regulation of the heart. They suggest that, in normal conscious rats, the central tachycardia of bromocriptine appears to predominate and to mask the bradycardia of this agonist at peripheral dopamine D2 receptors.","[{'text': 'isoproterenol', 'type': 'Chemical', 'start': 39, 'end': 52, 'mesh': 'D007545'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 56, 'end': 69, 'mesh': 'D001971'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 78, 'end': 89, 'mesh': 'D013610'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 132, 'end': 145, 'mesh': 'D001971'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 154, 'end': 165, 'mesh': 'D013610'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 231, 'end': 239, 'mesh': 'D004298'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 289, 'end': 302, 'mesh': 'D007545'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 492, 'end': 505, 'mesh': 'D007545'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 520, 'end': 533, 'mesh': 'D001971'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 542, 'end': 553, 'mesh': 'D013610'}, {'text': 'Isoproterenol', 'type': 'Chemical', 'start': 573, 'end': 586, 'mesh': 'D007545'}, {'text': 'cardiac hypertrophy', 'type': 'Disease', 'start': 619, 'end': 638, 'mesh': 'D006332'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 726, 'end': 739, 'mesh': 'D001971'}, {'text': 'hypotension', 'type': 'Disease', 'start': 776, 'end': 787, 'mesh': 'D007022'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 792, 'end': 803, 'mesh': 'D013610'}, {'text': 'Bromocriptine', 'type': 'Chemical', 'start': 805, 'end': 818, 'mesh': 'D001971'}, {'text': 'hypotension', 'type': 'Disease', 'start': 827, 'end': 838, 'mesh': 'D007022'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 857, 'end': 870, 'mesh': 'D007545'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 891, 'end': 902, 'mesh': 'D013610'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 931, 'end': 942, 'mesh': 'D001919'}, {'text': 'domperidone', 'type': 'Chemical', 'start': 986, 'end': 997, 'mesh': 'D004294'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1069, 'end': 1082, 'mesh': 'D007545'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1142, 'end': 1155, 'mesh': 'D007545'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1177, 'end': 1190, 'mesh': 'D007545'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1335, 'end': 1348, 'mesh': 'D007545'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1472, 'end': 1485, 'mesh': 'D007545'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 1531, 'end': 1544, 'mesh': 'D001971'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 1553, 'end': 1564, 'mesh': 'D013610'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 1568, 'end': 1579, 'mesh': 'D001919'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 1788, 'end': 1799, 'mesh': 'D013610'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 1803, 'end': 1816, 'mesh': 'D001971'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 1856, 'end': 1867, 'mesh': 'D001919'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1898, 'end': 1906, 'mesh': 'D004298'}]"
+225,10737864,A developmental analysis of clonidine's effects on cardiac rate and ultrasound production in infant rats.,"Under controlled conditions, infant rats emit ultrasonic vocalizations during extreme cold exposure and after administration of the alpha(2) adrenoceptor agonist, clonidine. Previous investigations have determined that, in response to clonidine, ultrasound production increases through the 2nd-week postpartum and decreases thereafter. Given that sympathetic neural dominance exhibits a similar developmental pattern, and given that clonidine induces sympathetic withdrawal and bradycardia, we hypothesized that clonidine's developmental effects on cardiac rate and ultrasound production would mirror each other. Therefore, in the present experiment, the effects of clonidine administration (0.5 mg/kg) on cardiac rate and ultrasound production were examined in 2-, 8-, 15-, and 20-day-old rats. Age-related changes in ultrasound production corresponded with changes in cardiovascular variables, including baseline cardiac rate and clonidine-induced bradycardia. This experiment is discussed with regard to the hypothesis that ultrasound production is the acoustic by-product of a physiological maneuver that compensates for clonidine's detrimental effects on cardiovascular function.","[{'text': 'clonidine', 'type': 'Chemical', 'start': 28, 'end': 37, 'mesh': 'D003000'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 269, 'end': 278, 'mesh': 'D003000'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 341, 'end': 350, 'mesh': 'D003000'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 539, 'end': 548, 'mesh': 'D003000'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 584, 'end': 595, 'mesh': 'D001919'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 618, 'end': 627, 'mesh': 'D003000'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 772, 'end': 781, 'mesh': 'D003000'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 1038, 'end': 1047, 'mesh': 'D003000'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 1056, 'end': 1067, 'mesh': 'D001919'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 1231, 'end': 1240, 'mesh': 'D003000'}]"
+226,10743446,Differential effects of systemically administered ketamine and lidocaine on dynamic and static hyperalgesia induced by intradermal capsaicin in humans.,"We have examined the effect of systemic administration of ketamine and lidocaine on brush-evoked (dynamic) pain and punctate-evoked (static) hyperalgesia induced by capsaicin. In a randomized, double-blind, placebo-controlled, crossover study, we studied 12 volunteers in three experiments. Capsaicin 100 micrograms was injected intradermally on the volar forearm followed by an i.v. infusion of ketamine (bolus 0.1 mg kg-1 over 10 min followed by infusion of 7 micrograms kg-1 min-1), lidocaine 5 mg kg-1 or saline for 50 min. Infusion started 15 min after injection of capsaicin. The following were measured: spontaneous pain, pain evoked by punctate and brush stimuli (VAS), and areas of brush-evoked and punctate-evoked hyperalgesia. Ketamine reduced both the area of brush-evoked and punctate-evoked hyperalgesia significantly and it tended to reduce brush-evoked pain. Lidocaine reduced the area of punctate-evoked hyperalgesia significantly. It tended to reduce VAS scores of spontaneous pain but had no effect on evoked pain. The differential effects of ketamine and lidocaine on static and dynamic hyperalgesia suggest that the two types of hyperalgesia are mediated by separate mechanisms and have a distinct pharmacology.","[{'text': 'ketamine', 'type': 'Chemical', 'start': 50, 'end': 58, 'mesh': 'D007649'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 63, 'end': 72, 'mesh': 'D008012'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 95, 'end': 107, 'mesh': 'D006930'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 131, 'end': 140, 'mesh': 'D002211'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 210, 'end': 218, 'mesh': 'D007649'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 223, 'end': 232, 'mesh': 'D008012'}, {'text': 'pain', 'type': 'Disease', 'start': 259, 'end': 263, 'mesh': 'D010146'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 293, 'end': 305, 'mesh': 'D006930'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 317, 'end': 326, 'mesh': 'D002211'}, {'text': 'Capsaicin', 'type': 'Chemical', 'start': 443, 'end': 452, 'mesh': 'D002211'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 548, 'end': 556, 'mesh': 'D007649'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 638, 'end': 647, 'mesh': 'D008012'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 723, 'end': 732, 'mesh': 'D002211'}, {'text': 'pain', 'type': 'Disease', 'start': 775, 'end': 779, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 781, 'end': 785, 'mesh': 'D010146'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 876, 'end': 888, 'mesh': 'D006930'}, {'text': 'Ketamine', 'type': 'Chemical', 'start': 890, 'end': 898, 'mesh': 'D007649'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 957, 'end': 969, 'mesh': 'D006930'}, {'text': 'pain', 'type': 'Disease', 'start': 1021, 'end': 1025, 'mesh': 'D010146'}, {'text': 'Lidocaine', 'type': 'Chemical', 'start': 1027, 'end': 1036, 'mesh': 'D008012'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 1073, 'end': 1085, 'mesh': 'D006930'}, {'text': 'pain', 'type': 'Disease', 'start': 1147, 'end': 1151, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 1180, 'end': 1184, 'mesh': 'D010146'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 1214, 'end': 1222, 'mesh': 'D007649'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 1227, 'end': 1236, 'mesh': 'D008012'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 1259, 'end': 1271, 'mesh': 'D006930'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 1302, 'end': 1314, 'mesh': 'D006930'}]"
+227,11007689,Cyclosporine and tacrolimus-associated thrombotic microangiopathy.,"The development of thrombotic microangiopathy (TMA) associated with the use of cyclosporine has been well documented. Treatments have included discontinuation or reduction of cyclosporine dose with or without concurrent plasma exchange, plasma infusion, anticoagulation, and intravenous immunoglobulin G infusion. However, for recipients of organ transplantation, removing the inciting agent is not without the attendant risk of precipitating acute rejection and graft loss. The last decade has seen the emergence of tacrolimus as a potent immunosuppressive agent with mechanisms of action virtually identical to those of cyclosporine. As a result, switching to tacrolimus has been reported to be a viable therapeutic option in the setting of cyclosporine-induced TMA. With the more widespread application of tacrolimus in organ transplantation, tacrolimus-associated TMA has also been recognized. However, literature regarding the incidence of the recurrence of TMA in patients exposed sequentially to cyclosporine and tacrolimus is limited. We report a case of a living donor renal transplant recipient who developed cyclosporine-induced TMA that responded to the withdrawal of cyclosporine in conjunction with plasmapheresis and fresh frozen plasma replacement therapy. Introduction of tacrolimus as an alternative immunosuppressive agent resulted in the recurrence of TMA and the subsequent loss of the renal allograft. Patients who are switched from cyclosporine to tacrolimus or vice versa should be closely monitored for the signs and symptoms of recurrent TMA.","[{'text': 'Cyclosporine', 'type': 'Chemical', 'start': 0, 'end': 12, 'mesh': 'D016572'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 17, 'end': 27, 'mesh': 'D016559'}, {'text': 'thrombotic microangiopathy', 'type': 'Disease', 'start': 39, 'end': 65, 'mesh': 'D057049'}, {'text': 'thrombotic microangiopathy', 'type': 'Disease', 'start': 86, 'end': 112, 'mesh': 'D057049'}, {'text': 'TMA', 'type': 'Disease', 'start': 114, 'end': 117, 'mesh': 'D057049'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 146, 'end': 158, 'mesh': 'D016572'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 242, 'end': 254, 'mesh': 'D016572'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 584, 'end': 594, 'mesh': 'D016559'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 689, 'end': 701, 'mesh': 'D016572'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 729, 'end': 739, 'mesh': 'D016559'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 810, 'end': 822, 'mesh': 'D016572'}, {'text': 'TMA', 'type': 'Disease', 'start': 831, 'end': 834, 'mesh': 'D057049'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 876, 'end': 886, 'mesh': 'D016559'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 913, 'end': 923, 'mesh': 'D016559'}, {'text': 'TMA', 'type': 'Disease', 'start': 935, 'end': 938, 'mesh': 'D057049'}, {'text': 'TMA', 'type': 'Disease', 'start': 1030, 'end': 1033, 'mesh': 'D057049'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 1070, 'end': 1082, 'mesh': 'D016572'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 1087, 'end': 1097, 'mesh': 'D016559'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 1186, 'end': 1198, 'mesh': 'D016572'}, {'text': 'TMA', 'type': 'Disease', 'start': 1207, 'end': 1210, 'mesh': 'D057049'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 1247, 'end': 1259, 'mesh': 'D016572'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 1356, 'end': 1366, 'mesh': 'D016559'}, {'text': 'TMA', 'type': 'Disease', 'start': 1439, 'end': 1442, 'mesh': 'D057049'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 1522, 'end': 1534, 'mesh': 'D016572'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 1538, 'end': 1548, 'mesh': 'D016559'}, {'text': 'TMA', 'type': 'Disease', 'start': 1631, 'end': 1634, 'mesh': 'D057049'}]"
+228,11256525,Repeated transient anuria following losartan administration in a patient with a solitary kidney.,"We report the case of a 70-year-old hypertensive man with a solitary kidney and chronic renal insufficiency who developed two episodes of transient anuria after losartan administration. He was hospitalized for a myocardial infarction with pulmonary edema, treated with high-dose diuretics. Due to severe systolic dysfunction losartan was prescribed. Surprisingly, the first dose of 50 mg of losartan resulted in a sudden anuria, which lasted eight hours despite high-dose furosemide and amine infusion. One week later, by mistake, losartan was prescribed again and after the second dose of 50 mg, the patient developed a second episode of transient anuria lasting 10 hours. During these two episodes, his blood pressure diminished but no severe hypotension was noted. Ultimately, an arteriography showed a 70-80% renal artery stenosis. In this patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, angiotensin II receptor blockade by losartan probably induced a critical fall in glomerular filtration pressure. This case report highlights the fact that the angiotensin II receptor antagonist losartan can cause serious unexpected complications in patients with renovascular disease and should be used with extreme caution in this setting.","[{'text': 'anuria', 'type': 'Disease', 'start': 19, 'end': 25, 'mesh': 'D001002'}, {'text': 'losartan', 'type': 'Chemical', 'start': 36, 'end': 44, 'mesh': 'D019808'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 133, 'end': 145, 'mesh': 'D006973'}, {'text': 'chronic renal insufficiency', 'type': 'Disease', 'start': 177, 'end': 204, 'mesh': 'D051436'}, {'text': 'anuria', 'type': 'Disease', 'start': 245, 'end': 251, 'mesh': 'D001002'}, {'text': 'losartan', 'type': 'Chemical', 'start': 258, 'end': 266, 'mesh': 'D019808'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 309, 'end': 330, 'mesh': 'D009203'}, {'text': 'pulmonary edema', 'type': 'Disease', 'start': 336, 'end': 351, 'mesh': 'D011654'}, {'text': 'systolic dysfunction', 'type': 'Disease', 'start': 401, 'end': 421, 'mesh': 'D006331'}, {'text': 'losartan', 'type': 'Chemical', 'start': 422, 'end': 430, 'mesh': 'D019808'}, {'text': 'losartan', 'type': 'Chemical', 'start': 488, 'end': 496, 'mesh': 'D019808'}, {'text': 'anuria', 'type': 'Disease', 'start': 518, 'end': 524, 'mesh': 'D001002'}, {'text': 'furosemide', 'type': 'Chemical', 'start': 569, 'end': 579, 'mesh': 'D005665'}, {'text': 'amine', 'type': 'Chemical', 'start': 584, 'end': 589, 'mesh': 'D000588'}, {'text': 'losartan', 'type': 'Chemical', 'start': 628, 'end': 636, 'mesh': 'D019808'}, {'text': 'anuria', 'type': 'Disease', 'start': 746, 'end': 752, 'mesh': 'D001002'}, {'text': 'hypotension', 'type': 'Disease', 'start': 842, 'end': 853, 'mesh': 'D007022'}, {'text': 'renal artery stenosis', 'type': 'Disease', 'start': 910, 'end': 931, 'mesh': 'D012078'}, {'text': 'renal artery stenosis', 'type': 'Disease', 'start': 950, 'end': 971, 'mesh': 'D012078'}, {'text': 'heart failure', 'type': 'Disease', 'start': 986, 'end': 999, 'mesh': 'D006333'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 1076, 'end': 1087, 'mesh': 'D000809'}, {'text': 'angiotensin II', 'type': 'Chemical', 'start': 1125, 'end': 1139, 'mesh': 'D000804'}, {'text': 'losartan', 'type': 'Chemical', 'start': 1161, 'end': 1169, 'mesh': 'D019808'}, {'text': 'angiotensin II', 'type': 'Chemical', 'start': 1284, 'end': 1298, 'mesh': 'D000804'}, {'text': 'losartan', 'type': 'Chemical', 'start': 1319, 'end': 1327, 'mesh': 'D019808'}, {'text': 'renovascular disease', 'type': 'Disease', 'start': 1388, 'end': 1408, 'mesh': 'D014652'}]"
+229,11334364,"In vivo protection of dna damage associated apoptotic and necrotic cell deaths during acetaminophen-induced nephrotoxicity, amiodarone-induced lung toxicity and doxorubicin-induced cardiotoxicity by a novel IH636 grape seed proanthocyanidin extract.","Grape seed extract, primarily a mixture of proanthocyanidins, has been shown to modulate a wide-range of biological, pharmacological and toxicological effects which are mainly cytoprotective. This study assessed the ability of IH636 grape seed proanthocyanidin extract (GSPE) to prevent acetaminophen (AAP)-induced nephrotoxicity, amiodarone (AMI)-induced lung toxicity, and doxorubicin (DOX)-induced cardiotoxicity in mice. Experimental design consisted of four groups: control (vehicle alone), GSPE alone, drug alone and GSPE+drug. For the cytoprotection study, animals were orally gavaged 100 mg/Kg GSPE for 7-10 days followed by i.p. injections of organ specific three drugs (AAP: 500 mg/Kg for 24 h; AMI: 50 mg/Kg/day for four days; DOX: 20 mg/Kg for 48 h). Parameters of study included analysis of serum chemistry (ALT, BUN and CPK), and orderly fragmentation of genomic DNA (both endonuclease-dependent and independent) in addition to microscopic evaluation of damage and/or protection in corresponding PAS stained tissues. Results indicate that GSPE preexposure prior to AAP, AMI and DOX, provided near complete protection in terms of serum chemistry changes (ALT, BUN and CPK), and significantly reduced DNA fragmentation. Histopathological examination of kidney, heart and lung sections revealed moderate to massive tissue damage with a variety of morphological aberrations by all the three drugs in the absence of GSPE preexposure than in its presence. GSPE+drug exposed tissues exhibited minor residual damage or near total recovery. Additionally, histopathological alterations mirrored both serum chemistry changes and the pattern of DNA fragmentation. Interestingly, all the drugs, such as, AAP, AMI and DOX induced apoptotic death in addition to necrosis in the respective organs which was very effectively blocked by GSPE. Since AAP, AMI and DOX undergo biotransformation and are known to produce damaging radicals in vivo, the protection by GSPE may be linked to both inhibition of metabolism and/or detoxification of cytotoxic radicals. In addition, its' presumed contribution to DNA repair may be another important attribute, which played a role in the chemoprevention process. Additionally, this may have been the first report on AMI-induced apoptotic death in the lung tissue. Taken together, these events undoubtedly establish GSPE's abundant bioavailability, and the power to defend multiple target organs from toxic assaults induced by structurally diverse and functionally different entities in vivo.","[{'text': 'necrotic', 'type': 'Disease', 'start': 58, 'end': 66, 'mesh': 'D009336'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 86, 'end': 99, 'mesh': 'D000082'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 108, 'end': 122, 'mesh': 'D007674'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 124, 'end': 134, 'mesh': 'D000638'}, {'text': 'lung toxicity', 'type': 'Disease', 'start': 143, 'end': 156, 'mesh': 'D008171'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 161, 'end': 172, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 181, 'end': 195, 'mesh': 'D066126'}, {'text': 'IH636 grape seed proanthocyanidin extract', 'type': 'Chemical', 'start': 207, 'end': 248, 'mesh': 'C511402'}, {'text': 'Grape seed extract', 'type': 'Chemical', 'start': 250, 'end': 268, 'mesh': 'C511402'}, {'text': 'proanthocyanidins', 'type': 'Chemical', 'start': 293, 'end': 310, 'mesh': 'D044945'}, {'text': 'IH636 grape seed proanthocyanidin extract', 'type': 'Chemical', 'start': 477, 'end': 518, 'mesh': 'C511402'}, {'text': 'GSPE', 'type': 'Chemical', 'start': 520, 'end': 524, 'mesh': 'C511402'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 537, 'end': 550, 'mesh': 'D000082'}, {'text': 'AAP', 'type': 'Chemical', 'start': 552, 'end': 555, 'mesh': 'D000082'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 565, 'end': 579, 'mesh': 'D007674'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 581, 'end': 591, 'mesh': 'D000638'}, {'text': 'AMI', 'type': 'Chemical', 'start': 593, 'end': 596, 'mesh': 'D000638'}, {'text': 'lung toxicity', 'type': 'Disease', 'start': 606, 'end': 619, 'mesh': 'D008171'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 625, 'end': 636, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 638, 'end': 641, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 651, 'end': 665, 'mesh': 'D066126'}, {'text': 'GSPE', 'type': 'Chemical', 'start': 746, 'end': 750, 'mesh': 'C511402'}, {'text': 'GSPE', 'type': 'Chemical', 'start': 773, 'end': 777, 'mesh': 'C511402'}, {'text': 'GSPE', 'type': 'Chemical', 'start': 852, 'end': 856, 'mesh': 'C511402'}, {'text': 'AAP', 'type': 'Chemical', 'start': 930, 'end': 933, 'mesh': 'D000082'}, {'text': 'AMI', 'type': 'Chemical', 'start': 955, 'end': 958, 'mesh': 'D000638'}, {'text': 'DOX', 'type': 'Chemical', 'start': 988, 'end': 991, 'mesh': 'D004317'}, {'text': 'GSPE', 'type': 'Chemical', 'start': 1303, 'end': 1307, 'mesh': 'C511402'}, {'text': 'AAP', 'type': 'Chemical', 'start': 1329, 'end': 1332, 'mesh': 'D000082'}, {'text': 'AMI', 'type': 'Chemical', 'start': 1334, 'end': 1337, 'mesh': 'D000638'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1342, 'end': 1345, 'mesh': 'D004317'}, {'text': 'tissue damage', 'type': 'Disease', 'start': 1576, 'end': 1589, 'mesh': 'D017695'}, {'text': 'GSPE', 'type': 'Chemical', 'start': 1675, 'end': 1679, 'mesh': 'C511402'}, {'text': 'GSPE', 'type': 'Chemical', 'start': 1714, 'end': 1718, 'mesh': 'C511402'}, {'text': 'AAP', 'type': 'Chemical', 'start': 1955, 'end': 1958, 'mesh': 'D000082'}, {'text': 'AMI', 'type': 'Chemical', 'start': 1960, 'end': 1963, 'mesh': 'D000638'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1968, 'end': 1971, 'mesh': 'D004317'}, {'text': 'necrosis', 'type': 'Disease', 'start': 2011, 'end': 2019, 'mesh': 'D009336'}, {'text': 'GSPE', 'type': 'Chemical', 'start': 2083, 'end': 2087, 'mesh': 'C511402'}, {'text': 'AAP', 'type': 'Chemical', 'start': 2095, 'end': 2098, 'mesh': 'D000082'}, {'text': 'AMI', 'type': 'Chemical', 'start': 2100, 'end': 2103, 'mesh': 'D000638'}, {'text': 'DOX', 'type': 'Chemical', 'start': 2108, 'end': 2111, 'mesh': 'D004317'}, {'text': 'GSPE', 'type': 'Chemical', 'start': 2208, 'end': 2212, 'mesh': 'C511402'}, {'text': 'AMI', 'type': 'Chemical', 'start': 2500, 'end': 2503, 'mesh': 'D000638'}, {'text': 'GSPE', 'type': 'Chemical', 'start': 2599, 'end': 2603, 'mesh': 'C511402'}]"
+230,11642480,Palpebral twitching in a depressed adolescent on citalopram.,Current estimates suggest that between 0.4% and 8.3% of children and adolescents are affected by major depression. We report a favorable response to treatment with citalopram by a 15-year-old boy with major depression who exhibited palpebral twitching during his first 2 weeks of treatment. This may have been a side effect of citalopram as it remitted with redistribution of doses.,"[{'text': 'Palpebral twitching', 'type': 'Disease', 'start': 0, 'end': 19, 'mesh': 'D004409'}, {'text': 'depressed', 'type': 'Disease', 'start': 25, 'end': 34, 'mesh': 'D003866'}, {'text': 'citalopram', 'type': 'Chemical', 'start': 49, 'end': 59, 'mesh': 'D015283'}, {'text': 'major depression', 'type': 'Disease', 'start': 158, 'end': 174, 'mesh': 'D003865'}, {'text': 'citalopram', 'type': 'Chemical', 'start': 225, 'end': 235, 'mesh': 'D015283'}, {'text': 'major depression', 'type': 'Disease', 'start': 262, 'end': 278, 'mesh': 'D003865'}, {'text': 'palpebral twitching', 'type': 'Disease', 'start': 293, 'end': 312, 'mesh': 'D004409'}, {'text': 'citalopram', 'type': 'Chemical', 'start': 388, 'end': 398, 'mesh': 'D015283'}]"
+231,12063090,Metamizol potentiates morphine antinociception but not constipation after chronic treatment.,"This work evaluates the antinociceptive and constipating effects of the combination of 3.2 mg/kg s.c. morphine with 177.8 mg/kg s.c. metamizol in acutely and chronically treated (once a day for 12 days) rats. On the 13th day, antinociceptive effects were assessed using a model of inflammatory nociception, pain-induced functional impairment model, and the charcoal meal test was used to evaluate the intestinal transit. Simultaneous administration of morphine with metamizol resulted in a markedly antinociceptive potentiation and an increasing of the duration of action after a single (298+/-7 vs. 139+/-36 units area (ua); P<0.001) and repeated administration (280+/-17 vs. 131+/-22 ua; P<0.001). Antinociceptive effect of morphine was reduced in chronically treated rats (39+/-10 vs. 18+/-5 au) while the combination-induced antinociception was remained similar as an acute treatment (298+/-7 vs. 280+/-17 au). Acute antinociceptive effects of the combination were partially prevented by 3.2 mg/kg naloxone s.c. (P<0.05), suggesting the partial involvement of the opioidergic system in the synergism observed. In independent groups, morphine inhibited the intestinal transit in 48+/-4% and 38+/-4% after acute and chronic treatment, respectively, suggesting that tolerance did not develop to the constipating effects. The combination inhibited intestinal transit similar to that produced by morphine regardless of the time of treatment, suggesting that metamizol did not potentiate morphine-induced constipation. These findings show a significant interaction between morphine and metamizol in chronically treated rats, suggesting that this combination could be useful for the treatment of chronic pain.","[{'text': 'Metamizol', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D004177'}, {'text': 'morphine', 'type': 'Chemical', 'start': 22, 'end': 30, 'mesh': 'D009020'}, {'text': 'constipation', 'type': 'Disease', 'start': 55, 'end': 67, 'mesh': 'D003248'}, {'text': 'constipating', 'type': 'Disease', 'start': 137, 'end': 149, 'mesh': 'D003248'}, {'text': 'morphine', 'type': 'Chemical', 'start': 195, 'end': 203, 'mesh': 'D009020'}, {'text': 'metamizol', 'type': 'Chemical', 'start': 226, 'end': 235, 'mesh': 'D004177'}, {'text': 'pain', 'type': 'Disease', 'start': 400, 'end': 404, 'mesh': 'D010146'}, {'text': 'charcoal', 'type': 'Chemical', 'start': 450, 'end': 458, 'mesh': 'D002606'}, {'text': 'morphine', 'type': 'Chemical', 'start': 545, 'end': 553, 'mesh': 'D009020'}, {'text': 'metamizol', 'type': 'Chemical', 'start': 559, 'end': 568, 'mesh': 'D004177'}, {'text': 'morphine', 'type': 'Chemical', 'start': 819, 'end': 827, 'mesh': 'D009020'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 1095, 'end': 1103, 'mesh': 'D009270'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1230, 'end': 1238, 'mesh': 'D009020'}, {'text': 'constipating', 'type': 'Disease', 'start': 1393, 'end': 1405, 'mesh': 'D003248'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1488, 'end': 1496, 'mesh': 'D009020'}, {'text': 'metamizol', 'type': 'Chemical', 'start': 1550, 'end': 1559, 'mesh': 'D004177'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1579, 'end': 1587, 'mesh': 'D009020'}, {'text': 'constipation', 'type': 'Disease', 'start': 1596, 'end': 1608, 'mesh': 'D003248'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1664, 'end': 1672, 'mesh': 'D009020'}, {'text': 'metamizol', 'type': 'Chemical', 'start': 1677, 'end': 1686, 'mesh': 'D004177'}, {'text': 'chronic pain', 'type': 'Disease', 'start': 1786, 'end': 1798, 'mesh': 'D059350'}]"
+232,12084448,Ifosfamide encephalopathy presenting with asterixis.,"CNS toxic effects of the antineoplastic agent ifosfamide (IFX) are frequent and include a variety of neurological symptoms that can limit drug use. We report a case of a 51-year-old man who developed severe, disabling negative myoclonus of the upper and lower extremities after the infusion of ifosfamide for plasmacytoma. He was awake, revealed no changes of mental status and at rest there were no further motor symptoms. Cranial magnetic resonance imaging and extensive laboratory studies failed to reveal structural lesions of the brain and metabolic abnormalities. An electroencephalogram showed continuous, generalized irregular slowing with admixed periodic triphasic waves indicating symptomatic encephalopathy. The administration of ifosfamide was discontinued and within 12 h the asterixis resolved completely. In the patient described, the presence of asterixis during infusion of ifosfamide, normal laboratory findings and imaging studies and the resolution of symptoms following the discontinuation of the drug suggest that negative myoclonus is associated with the use of IFX.","[{'text': 'Ifosfamide', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D007069'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 11, 'end': 25, 'mesh': 'D001927'}, {'text': 'asterixis', 'type': 'Disease', 'start': 42, 'end': 51, 'mesh': 'D020820'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 99, 'end': 109, 'mesh': 'D007069'}, {'text': 'IFX', 'type': 'Chemical', 'start': 111, 'end': 114, 'mesh': 'D007069'}, {'text': 'myoclonus', 'type': 'Disease', 'start': 280, 'end': 289, 'mesh': 'D009207'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 347, 'end': 357, 'mesh': 'D007069'}, {'text': 'plasmacytoma', 'type': 'Disease', 'start': 362, 'end': 374, 'mesh': 'D010954'}, {'text': 'structural lesions of the brain', 'type': 'Disease', 'start': 562, 'end': 593, 'mesh': 'D001927'}, {'text': 'metabolic abnormalities', 'type': 'Disease', 'start': 598, 'end': 621, 'mesh': 'D008659'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 757, 'end': 771, 'mesh': 'D001927'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 795, 'end': 805, 'mesh': 'D007069'}, {'text': 'asterixis', 'type': 'Disease', 'start': 843, 'end': 852, 'mesh': 'D020820'}, {'text': 'asterixis', 'type': 'Disease', 'start': 916, 'end': 925, 'mesh': 'D020820'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 945, 'end': 955, 'mesh': 'D007069'}, {'text': 'myoclonus', 'type': 'Disease', 'start': 1099, 'end': 1108, 'mesh': 'D009207'}, {'text': 'IFX', 'type': 'Chemical', 'start': 1139, 'end': 1142, 'mesh': 'D007069'}]"
+233,12684739,Sub-chronic low dose gamma-vinyl GABA (vigabatrin) inhibits cocaine-induced increases in nucleus accumbens dopamine.,"RATIONALE: gamma-Vinyl GABA (GVG) irreversibly inhibits GABA-transaminase. This non-receptor mediated inhibition requires de novo synthesis for restoration of functional GABA catabolism. OBJECTIVES: Given its preclinical success for treating substance abuse and the increased risk of visual field defects (VFD) associated with cumulative lifetime exposure, we explored the effects of sub-chronic low dose GVG on cocaine-induced increases in nucleus accumbens (NAcc) dopamine (DA). METHODS: Using in vivo microdialysis, we compared acute exposure (450 mg/kg) to an identical sub-chronic exposure (150 mg/kg per day for 3 days), followed by 1- or 3-day washout. Finally, we examined the low dose of 150 mg/kg (50 mg/kg per day) using a similar washout period. RESULTS: Sub-chronic GVG exposure inhibited the effect of cocaine for 3 days, which exceeded in magnitude and duration the identical acute dose. CONCLUSIONS: Sub-chronic low dose GVG potentiates and extends the inhibition of cocaine-induced increases in dopamine, effectively reducing cumulative exposures and the risk for VFDS.","[{'text': 'gamma-vinyl GABA', 'type': 'Chemical', 'start': 21, 'end': 37, 'mesh': 'D020888'}, {'text': 'vigabatrin', 'type': 'Chemical', 'start': 39, 'end': 49, 'mesh': 'D020888'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 60, 'end': 67, 'mesh': 'D003042'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 107, 'end': 115, 'mesh': 'D004298'}, {'text': 'gamma-Vinyl GABA', 'type': 'Chemical', 'start': 128, 'end': 144, 'mesh': 'D020888'}, {'text': 'GVG', 'type': 'Chemical', 'start': 146, 'end': 149, 'mesh': 'D020888'}, {'text': 'GABA', 'type': 'Chemical', 'start': 173, 'end': 177, 'mesh': 'D005680'}, {'text': 'GABA', 'type': 'Chemical', 'start': 287, 'end': 291, 'mesh': 'D005680'}, {'text': 'substance abuse', 'type': 'Disease', 'start': 359, 'end': 374, 'mesh': 'D019966'}, {'text': 'visual field defects', 'type': 'Disease', 'start': 401, 'end': 421, 'mesh': 'D005128'}, {'text': 'VFD', 'type': 'Disease', 'start': 423, 'end': 426, 'mesh': 'D005128'}, {'text': 'GVG', 'type': 'Chemical', 'start': 522, 'end': 525, 'mesh': 'D020888'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 529, 'end': 536, 'mesh': 'D003042'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 583, 'end': 591, 'mesh': 'D004298'}, {'text': 'DA', 'type': 'Chemical', 'start': 593, 'end': 595, 'mesh': 'D004298'}, {'text': 'GVG', 'type': 'Chemical', 'start': 896, 'end': 899, 'mesh': 'D020888'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 933, 'end': 940, 'mesh': 'D003042'}, {'text': 'GVG', 'type': 'Chemical', 'start': 1054, 'end': 1057, 'mesh': 'D020888'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1100, 'end': 1107, 'mesh': 'D003042'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1129, 'end': 1137, 'mesh': 'D004298'}]"
+234,12716030,Amount of bleeding and hematoma size in the collagenase-induced intracerebral hemorrhage rat model.,"The aggravated risk on intracerebral hemorrhage (ICH) with drugs used for stroke patients should be estimated carefully. We therefore established sensitive quantification methods and provided a rat ICH model for detection of ICH deterioration. In ICH intrastriatally induced by 0.014-unit, 0.070-unit, and 0.350-unit collagenase, the amount of bleeding was measured using a hemoglobin assay developed in the present study and was compared with the morphologically determined hematoma volume. The blood amounts and hematoma volumes were significantly correlated, and the hematoma induced by 0.014-unit collagenase was adequate to detect ICH deterioration. In ICH induction using 0.014-unit collagenase, heparin enhanced the hematoma volume 3.4-fold over that seen in control ICH animals and the bleeding 7.6-fold. Data suggest that this sensitive hemoglobin assay is useful for ICH detection, and that a model with a small ICH induced with a low-dose collagenase should be used for evaluation of drugs that may affect ICH.","[{'text': 'bleeding', 'type': 'Disease', 'start': 10, 'end': 18, 'mesh': 'D006470'}, {'text': 'hematoma', 'type': 'Disease', 'start': 23, 'end': 31, 'mesh': 'D006406'}, {'text': 'intracerebral hemorrhage', 'type': 'Disease', 'start': 64, 'end': 88, 'mesh': 'D002543'}, {'text': 'intracerebral hemorrhage', 'type': 'Disease', 'start': 123, 'end': 147, 'mesh': 'D002543'}, {'text': 'ICH', 'type': 'Disease', 'start': 149, 'end': 152, 'mesh': 'D002543'}, {'text': 'stroke', 'type': 'Disease', 'start': 174, 'end': 180, 'mesh': 'D020521'}, {'text': 'ICH', 'type': 'Disease', 'start': 298, 'end': 301, 'mesh': 'D002543'}, {'text': 'ICH', 'type': 'Disease', 'start': 325, 'end': 328, 'mesh': 'D002543'}, {'text': 'ICH', 'type': 'Disease', 'start': 347, 'end': 350, 'mesh': 'D002543'}, {'text': 'bleeding', 'type': 'Disease', 'start': 444, 'end': 452, 'mesh': 'D006470'}, {'text': 'hematoma', 'type': 'Disease', 'start': 575, 'end': 583, 'mesh': 'D006406'}, {'text': 'hematoma', 'type': 'Disease', 'start': 614, 'end': 622, 'mesh': 'D006406'}, {'text': 'hematoma', 'type': 'Disease', 'start': 670, 'end': 678, 'mesh': 'D006406'}, {'text': 'ICH', 'type': 'Disease', 'start': 736, 'end': 739, 'mesh': 'D002543'}, {'text': 'ICH', 'type': 'Disease', 'start': 758, 'end': 761, 'mesh': 'D002543'}, {'text': 'heparin', 'type': 'Chemical', 'start': 802, 'end': 809, 'mesh': 'D006493'}, {'text': 'hematoma', 'type': 'Disease', 'start': 823, 'end': 831, 'mesh': 'D006406'}, {'text': 'ICH', 'type': 'Disease', 'start': 874, 'end': 877, 'mesh': 'D002543'}, {'text': 'bleeding', 'type': 'Disease', 'start': 894, 'end': 902, 'mesh': 'D006470'}, {'text': 'ICH', 'type': 'Disease', 'start': 977, 'end': 980, 'mesh': 'D002543'}, {'text': 'ICH', 'type': 'Disease', 'start': 1022, 'end': 1025, 'mesh': 'D002543'}, {'text': 'ICH', 'type': 'Disease', 'start': 1117, 'end': 1120, 'mesh': 'D002543'}]"
+235,12757899,Estradiol reduces seizure-induced hippocampal injury in ovariectomized female but not in male rats.,"Estrogens protect ovariectomized rats from hippocampal injury induced by kainic acid-induced status epilepticus (SE). We compared the effects of 17beta-estradiol in adult male and ovariectomized female rats subjected to lithium-pilocarpine-induced SE. Rats received subcutaneous injections of 17beta-estradiol (2 microg/rat) or oil once daily for four consecutive days. SE was induced 20 h following the second injection and terminated 3 h later. The extent of silver-stained CA3 and CA1 hippocampal neurons was evaluated 2 days after SE. 17beta-Estradiol did not alter the onset of first clonus in ovariectomized rats but accelerated it in males. 17beta-Estradiol reduced the argyrophilic neurons in the CA1 and CA3-C sectors of ovariectomized rats. In males, estradiol increased the total damage score. These findings suggest that the effects of estradiol on seizure threshold and damage may be altered by sex-related differences in the hormonal environment.","[{'text': 'Estradiol', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D004958'}, {'text': 'seizure', 'type': 'Disease', 'start': 18, 'end': 25, 'mesh': 'D012640'}, {'text': 'hippocampal injury', 'type': 'Disease', 'start': 34, 'end': 52, 'mesh': 'D001930'}, {'text': 'hippocampal injury', 'type': 'Disease', 'start': 143, 'end': 161, 'mesh': 'D001930'}, {'text': 'kainic acid', 'type': 'Chemical', 'start': 173, 'end': 184, 'mesh': 'D007608'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 193, 'end': 211, 'mesh': 'D013226'}, {'text': 'SE', 'type': 'Disease', 'start': 213, 'end': 215, 'mesh': 'D013226'}, {'text': '17beta-estradiol', 'type': 'Chemical', 'start': 245, 'end': 261, 'mesh': 'D004958'}, {'text': 'lithium', 'type': 'Chemical', 'start': 320, 'end': 327, 'mesh': 'D008094'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 328, 'end': 339, 'mesh': 'D010862'}, {'text': 'SE', 'type': 'Disease', 'start': 348, 'end': 350, 'mesh': 'D013226'}, {'text': '17beta-estradiol', 'type': 'Chemical', 'start': 393, 'end': 409, 'mesh': 'D004958'}, {'text': 'SE', 'type': 'Disease', 'start': 470, 'end': 472, 'mesh': 'D013226'}, {'text': 'silver', 'type': 'Chemical', 'start': 561, 'end': 567, 'mesh': 'D012834'}, {'text': 'SE', 'type': 'Disease', 'start': 635, 'end': 637, 'mesh': 'D013226'}, {'text': '17beta-Estradiol', 'type': 'Chemical', 'start': 639, 'end': 655, 'mesh': 'D004958'}, {'text': '17beta-Estradiol', 'type': 'Chemical', 'start': 748, 'end': 764, 'mesh': 'D004958'}, {'text': 'estradiol', 'type': 'Chemical', 'start': 861, 'end': 870, 'mesh': 'D004958'}, {'text': 'estradiol', 'type': 'Chemical', 'start': 948, 'end': 957, 'mesh': 'D004958'}, {'text': 'seizure', 'type': 'Disease', 'start': 961, 'end': 968, 'mesh': 'D012640'}]"
+236,12905102,Delirium during clozapine treatment: incidence and associated risk factors.,"BACKGROUND: Incidence and risk factors for delirium during clozapine treatment require further clarification. METHODS: We used computerized pharmacy records to identify all adult psychiatric inpatients treated with clozapine (1995-96), reviewed their medical records to score incidence and severity of delirium, and tested associations with potential risk factors. RESULTS: Subjects (n = 139) were 72 women and 67 men, aged 40.8 +/- 12.1 years, hospitalized for 24.9 +/- 23.3 days, and given clozapine, gradually increased to an average daily dose of 282 +/- 203 mg (3.45 +/- 2.45 mg/kg) for 18.9 +/- 16.4 days. Delirium was diagnosed in 14 (10.1 % incidence, or 1.48 cases/person-years of exposure); 71.4 % of cases were moderate or severe. Associated factors were co-treatment with other centrally antimuscarinic agents, poor clinical outcome, older age, and longer hospitalization (by 17.5 days, increasing cost); sex, diagnosis or medical co-morbidity, and daily clozapine dose, which fell with age, were unrelated. CONCLUSIONS: Delirium was found in 10 % of clozapine-treated inpatients, particularly in older patients exposed to other central anticholinergics. Delirium was inconsistently recognized clinically in milder cases and was associated with increased length-of-stay and higher costs, and inferior clinical outcome.","[{'text': 'Delirium', 'type': 'Disease', 'start': 0, 'end': 8, 'mesh': 'D003693'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 16, 'end': 25, 'mesh': 'D003024'}, {'text': 'delirium', 'type': 'Disease', 'start': 119, 'end': 127, 'mesh': 'D003693'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 135, 'end': 144, 'mesh': 'D003024'}, {'text': 'psychiatric', 'type': 'Disease', 'start': 255, 'end': 266, 'mesh': 'D001523'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 291, 'end': 300, 'mesh': 'D003024'}, {'text': 'delirium', 'type': 'Disease', 'start': 378, 'end': 386, 'mesh': 'D003693'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 568, 'end': 577, 'mesh': 'D003024'}, {'text': 'Delirium', 'type': 'Disease', 'start': 688, 'end': 696, 'mesh': 'D003693'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 1043, 'end': 1052, 'mesh': 'D003024'}, {'text': 'Delirium', 'type': 'Disease', 'start': 1109, 'end': 1117, 'mesh': 'D003693'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 1139, 'end': 1148, 'mesh': 'D003024'}, {'text': 'Delirium', 'type': 'Disease', 'start': 1243, 'end': 1251, 'mesh': 'D003693'}]"
+237,14513889,Ketoconazole-induced neurologic sequelae.,"A 77-y-old patient developed weakness of extremities, legs paralysis, dysarthria and tremor 1 h after ingestion of 200 mg ketoconazole for the first time in his life. All complaints faded away within 24 h. Few days later, the patient used another 200 mg ketoconazole tablet, and within an hour experienced a similar clinical picture, which resolved again spontaneously within hours. Laboratory evaluations, including head CT scan, were normal. This case illustrates the need for close vigilance in adverse drug reactions, particularly in the elderly.","[{'text': 'Ketoconazole', 'type': 'Chemical', 'start': 0, 'end': 12, 'mesh': 'D007654'}, {'text': 'neurologic sequelae', 'type': 'Disease', 'start': 21, 'end': 40, 'mesh': 'D009422'}, {'text': 'weakness of extremities', 'type': 'Disease', 'start': 71, 'end': 94, 'mesh': 'D018908'}, {'text': 'legs paralysis', 'type': 'Disease', 'start': 96, 'end': 110, 'mesh': 'D010243'}, {'text': 'dysarthria', 'type': 'Disease', 'start': 112, 'end': 122, 'mesh': 'D004401'}, {'text': 'tremor', 'type': 'Disease', 'start': 127, 'end': 133, 'mesh': 'D014202'}, {'text': 'ketoconazole', 'type': 'Chemical', 'start': 164, 'end': 176, 'mesh': 'D007654'}, {'text': 'ketoconazole', 'type': 'Chemical', 'start': 296, 'end': 308, 'mesh': 'D007654'}, {'text': 'adverse drug reactions', 'type': 'Disease', 'start': 540, 'end': 562, 'mesh': 'D064420'}]"
+238,15009014,Noxious chemical stimulation of rat facial mucosa increases intracranial blood flow through a trigemino-parasympathetic reflex--an experimental model for vascular dysfunctions in cluster headache.,"Cluster headache is characterized by typical autonomic dysfunctions including facial and intracranial vascular disturbances. Both the trigeminal and the cranial parasympathetic systems may be involved in mediating these dysfunctions. An experimental model was developed in the rat to measure changes in lacrimation and intracranial blood flow following noxious chemical stimulation of facial mucosa. Blood flow was monitored in arteries of the exposed cranial dura mater and the parietal cortex using laser Doppler flowmetry. Capsaicin (0.01-1 mm) applied to oral or nasal mucosa induced increases in dural and cortical blood flow and provoked lacrimation. These responses were blocked by systemic pre-administration of hexamethonium chloride (20 mg/kg). The evoked increases in dural blood flow were also abolished by topical pre-administration of atropine (1 mm) and [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP (0.1 mm), a vasoactive intestinal polypeptide (VIP) antagonist, onto the exposed dura mater. We conclude that noxious stimulation of facial mucosa increases intracranial blood flow and lacrimation via a trigemino-parasympathetic reflex. The blood flow responses seem to be mediated by the release of acetylcholine and VIP within the meninges. Similar mechanisms may be involved in the pathogenesis of cluster headache.","[{'text': 'vascular dysfunctions', 'type': 'Disease', 'start': 154, 'end': 175, 'mesh': 'D002561'}, {'text': 'cluster headache', 'type': 'Disease', 'start': 179, 'end': 195, 'mesh': 'D003027'}, {'text': 'Cluster headache', 'type': 'Disease', 'start': 197, 'end': 213, 'mesh': 'D003027'}, {'text': 'intracranial vascular disturbances', 'type': 'Disease', 'start': 286, 'end': 320, 'mesh': 'D002561'}, {'text': 'Capsaicin', 'type': 'Chemical', 'start': 723, 'end': 732, 'mesh': 'D002211'}, {'text': 'increases in dural and cortical blood flow', 'type': 'Disease', 'start': 785, 'end': 827, 'mesh': 'D006940'}, {'text': 'hexamethonium chloride', 'type': 'Chemical', 'start': 917, 'end': 939, 'mesh': 'D018738'}, {'text': 'increases in dural blood flow', 'type': 'Disease', 'start': 963, 'end': 992, 'mesh': 'D006940'}, {'text': 'atropine', 'type': 'Chemical', 'start': 1046, 'end': 1054, 'mesh': 'D001285'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 1399, 'end': 1412, 'mesh': 'D000109'}, {'text': 'cluster headache', 'type': 'Disease', 'start': 1500, 'end': 1516, 'mesh': 'D003027'}]"
+239,15120741,Recurrent excitation in the dentate gyrus of a murine model of temporal lobe epilepsy.,"Similar to rats, systemic pilocarpine injection causes status epilepticus (SE) and the eventual development of spontaneous seizures and mossy fiber sprouting in C57BL/6 and CD1 mice, but the physiological correlates of these events have not been identified in mice. Population responses in granule cells of the dentate gyrus were examined in transverse slices of the ventral hippocampus from pilocarpine-treated and untreated mice. In Mg(2+)-free bathing medium containing bicuculline, conditions designed to increase excitability in the slices, electrical stimulation of the hilus resulted in a single population spike in granule cells from control mice and pilocarpine-treated mice that did not experience SE. In SE survivors, similar stimulation resulted in a population spike followed, at a variable latency, by negative DC shifts and repetitive afterdischarges of 3-60 s duration, which were blocked by ionotropic glutamate receptor antagonists. Focal glutamate photostimulation of the granule cell layer at sites distant from the recording pipette resulted in population responses of 1-30 s duration in slices from SE survivors but not other groups. These data support the hypothesis that SE-induced mossy fiber sprouting and synaptic reorganization are relevant characteristics of seizure development in these murine strains, resembling rat models of human temporal lobe epilepsy.","[{'text': 'temporal lobe epilepsy', 'type': 'Disease', 'start': 63, 'end': 85, 'mesh': 'D004833'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 113, 'end': 124, 'mesh': 'D010862'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 142, 'end': 160, 'mesh': 'D013226'}, {'text': 'SE', 'type': 'Disease', 'start': 162, 'end': 164, 'mesh': 'D013226'}, {'text': 'seizures', 'type': 'Disease', 'start': 210, 'end': 218, 'mesh': 'D012640'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 479, 'end': 490, 'mesh': 'D010862'}, {'text': 'Mg', 'type': 'Chemical', 'start': 522, 'end': 524, 'mesh': 'D008274'}, {'text': 'bicuculline', 'type': 'Chemical', 'start': 560, 'end': 571, 'mesh': 'D001640'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 746, 'end': 757, 'mesh': 'D010862'}, {'text': 'SE', 'type': 'Disease', 'start': 795, 'end': 797, 'mesh': 'D013226'}, {'text': 'SE', 'type': 'Disease', 'start': 802, 'end': 804, 'mesh': 'D013226'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 1006, 'end': 1015, 'mesh': 'D018698'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 1044, 'end': 1053, 'mesh': 'D018698'}, {'text': 'SE', 'type': 'Disease', 'start': 1208, 'end': 1210, 'mesh': 'D013226'}, {'text': 'SE', 'type': 'Disease', 'start': 1282, 'end': 1284, 'mesh': 'D013226'}, {'text': 'seizure', 'type': 'Disease', 'start': 1375, 'end': 1382, 'mesh': 'D012640'}, {'text': 'temporal lobe epilepsy', 'type': 'Disease', 'start': 1451, 'end': 1473, 'mesh': 'D004833'}]"
+240,15275829,The alpha3 and beta4 nicotinic acetylcholine receptor subunits are necessary for nicotine-induced seizures and hypolocomotion in mice.,"Binding of nicotine to nicotinic acetylcholine receptors (nAChRs) elicits a series of dose-dependent behaviors that go from altered exploration, sedation, and tremors, to seizures and death. nAChRs are pentameric ion channels usually composed of alpha and beta subunits. A gene cluster comprises the alpha3, alpha5 and beta4 subunits, which coassemble to form functional receptors. We examined the role of the beta4 subunits in nicotine-induced seizures and hypolocomotion in beta4 homozygous null (beta4 -/-) and alpha3 heterozygous (+/-) mice. beta4 -/- mice were less sensitive to the effects of nicotine both at low doses, measured as decreased exploration in an open field, and at high doses, measured as sensitivity to nicotine-induced seizures. Using in situ hybridization probes for the alpha3 and alpha5 subunits, we showed that alpha5 mRNA levels are unchanged, whereas alpha3 mRNA levels are selectively decreased in the mitral cell layer of the olfactory bulb, and the inferior and the superior colliculus of beta4 -/- brains. alpha3 +/- mice were partially resistant to nicotine-induced seizures when compared to wild-type littermates. mRNA levels for the alpha5 and the beta4 subunits were unchanged in alpha3 +/- brains. Together, these results suggest that the beta4 and the alpha3 subunits are mediators of nicotine-induced seizures and hypolocomotion.","[{'text': 'acetylcholine', 'type': 'Chemical', 'start': 31, 'end': 44, 'mesh': 'D000109'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 81, 'end': 89, 'mesh': 'D009538'}, {'text': 'seizures', 'type': 'Disease', 'start': 98, 'end': 106, 'mesh': 'D012640'}, {'text': 'hypolocomotion', 'type': 'Disease', 'start': 111, 'end': 125, 'mesh': 'D006948'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 146, 'end': 154, 'mesh': 'D009538'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 168, 'end': 181, 'mesh': 'D000109'}, {'text': 'tremors', 'type': 'Disease', 'start': 294, 'end': 301, 'mesh': 'D014202'}, {'text': 'seizures', 'type': 'Disease', 'start': 306, 'end': 314, 'mesh': 'D012640'}, {'text': 'death', 'type': 'Disease', 'start': 319, 'end': 324, 'mesh': 'D003643'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 563, 'end': 571, 'mesh': 'D009538'}, {'text': 'seizures', 'type': 'Disease', 'start': 580, 'end': 588, 'mesh': 'D012640'}, {'text': 'hypolocomotion', 'type': 'Disease', 'start': 593, 'end': 607, 'mesh': 'D006948'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 734, 'end': 742, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 860, 'end': 868, 'mesh': 'D009538'}, {'text': 'seizures', 'type': 'Disease', 'start': 877, 'end': 885, 'mesh': 'D012640'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 1218, 'end': 1226, 'mesh': 'D009538'}, {'text': 'seizures', 'type': 'Disease', 'start': 1235, 'end': 1243, 'mesh': 'D012640'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 1459, 'end': 1467, 'mesh': 'D009538'}, {'text': 'seizures', 'type': 'Disease', 'start': 1476, 'end': 1484, 'mesh': 'D012640'}, {'text': 'hypolocomotion', 'type': 'Disease', 'start': 1489, 'end': 1503, 'mesh': 'D006948'}]"
+241,15602202,Recurrent acute interstitial nephritis induced by azithromycin.,"A 14-year-old girl is reported with recurrent, azithromycin-induced, acute interstitial nephritis. The second episode was more severe than the first; and although both were treated with intensive corticosteroid therapy, renal function remained impaired. Although most cases of antibiotic induced acute interstitial nephritis are benign and self-limited, some patients are at risk for permanent renal injury.","[{'text': 'interstitial nephritis', 'type': 'Disease', 'start': 16, 'end': 38, 'mesh': 'D009395'}, {'text': 'azithromycin', 'type': 'Chemical', 'start': 50, 'end': 62, 'mesh': 'D017963'}, {'text': 'azithromycin', 'type': 'Chemical', 'start': 111, 'end': 123, 'mesh': 'D017963'}, {'text': 'interstitial nephritis', 'type': 'Disease', 'start': 139, 'end': 161, 'mesh': 'D009395'}, {'text': 'interstitial nephritis', 'type': 'Disease', 'start': 366, 'end': 388, 'mesh': 'D009395'}, {'text': 'renal injury', 'type': 'Disease', 'start': 458, 'end': 470, 'mesh': 'D007674'}]"
+242,16181582,Valproate-induced encephalopathy.,Valproate-induced encephalopathy is a rare syndrome that may manifest in otherwise normal epileptic individuals. It may even present in patients who have tolerated this medicine well in the past. It is usually but not necessarily associated with hyperammonemia. The EEG shows characteristic triphasic waves in most patients with this complication. A case of valproate-induced encephalopathy is presented. The problems in diagnosing this condition are subsequently discussed.,"[{'text': 'Valproate', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D014635'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 18, 'end': 32, 'mesh': 'D001927'}, {'text': 'Valproate', 'type': 'Chemical', 'start': 34, 'end': 43, 'mesh': 'D014635'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 52, 'end': 66, 'mesh': 'D001927'}, {'text': 'epileptic', 'type': 'Disease', 'start': 124, 'end': 133, 'mesh': 'D004827'}, {'text': 'hyperammonemia', 'type': 'Disease', 'start': 280, 'end': 294, 'mesh': 'D022124'}, {'text': 'valproate', 'type': 'Chemical', 'start': 392, 'end': 401, 'mesh': 'D014635'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 410, 'end': 424, 'mesh': 'D001927'}]"
+243,16298782,Nitro-L-arginine methyl ester: a potential protector against gentamicin ototoxicity.,"The nitric oxide (NO) inhibitor nitro-L-arginine methyl ester (L-NAME) may act as an otoprotectant against high-frequency hearing loss caused by gentamicin, but further studies are needed to confirm this.Aminoglycoside antibiotics are still widely used by virtue of their efficacy and low cost. Their ototoxicity is a serious health problem and, as their ototoxic mechanism involves the production of NO, we need to assess the use of NO inhibitors for the prevention of aminoglycoside-induced sensorineural hearing loss. In this experimental study we used 30 Sprague-Dawley rats, 27 of which had gentamicin instilled into the middle ear. The otoprotectant L-NAME was administered topically to 12/27 animals. Its effect was determined in terms of attenuation of hearing loss, measured by shifts in the auditory brainstem response threshold. L-NAME reduced gentamicin-induced hearing loss in the high-frequency range, but gave no protection in the middle or low frequencies.","[{'text': 'Nitro-L-arginine methyl ester', 'type': 'Chemical', 'start': 0, 'end': 29, 'mesh': 'D019331'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 61, 'end': 71, 'mesh': 'D005839'}, {'text': 'ototoxicity', 'type': 'Disease', 'start': 72, 'end': 83, 'mesh': 'D006311'}, {'text': 'nitric oxide', 'type': 'Chemical', 'start': 89, 'end': 101, 'mesh': 'D009569'}, {'text': 'NO', 'type': 'Chemical', 'start': 103, 'end': 105, 'mesh': 'D009569'}, {'text': 'nitro-L-arginine methyl ester', 'type': 'Chemical', 'start': 117, 'end': 146, 'mesh': 'D019331'}, {'text': 'L-NAME', 'type': 'Chemical', 'start': 148, 'end': 154, 'mesh': 'D019331'}, {'text': 'high-frequency hearing loss', 'type': 'Disease', 'start': 192, 'end': 219, 'mesh': 'D006316'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 230, 'end': 240, 'mesh': 'D005839'}, {'text': 'Aminoglycoside', 'type': 'Chemical', 'start': 289, 'end': 303, 'mesh': 'D000617'}, {'text': 'ototoxicity', 'type': 'Disease', 'start': 386, 'end': 397, 'mesh': 'D006311'}, {'text': 'ototoxic', 'type': 'Disease', 'start': 440, 'end': 448, 'mesh': 'D006311'}, {'text': 'NO', 'type': 'Chemical', 'start': 486, 'end': 488, 'mesh': 'D009569'}, {'text': 'NO', 'type': 'Chemical', 'start': 519, 'end': 521, 'mesh': 'D009569'}, {'text': 'aminoglycoside', 'type': 'Chemical', 'start': 555, 'end': 569, 'mesh': 'D000617'}, {'text': 'sensorineural hearing loss', 'type': 'Disease', 'start': 578, 'end': 604, 'mesh': 'D006319'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 681, 'end': 691, 'mesh': 'D005839'}, {'text': 'L-NAME', 'type': 'Chemical', 'start': 741, 'end': 747, 'mesh': 'D019331'}, {'text': 'hearing loss', 'type': 'Disease', 'start': 846, 'end': 858, 'mesh': 'D034381'}, {'text': 'L-NAME', 'type': 'Chemical', 'start': 925, 'end': 931, 'mesh': 'D019331'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 940, 'end': 950, 'mesh': 'D005839'}, {'text': 'hearing loss', 'type': 'Disease', 'start': 959, 'end': 971, 'mesh': 'D034381'}]"
+244,16428221,Cerebral vasculitis following oral methylphenidate intake in an adult: a case report.,"Methylphenidate is structurally and functionally similar to amphetamine. Cerebral vasculitis associated with amphetamine abuse is well documented, and in rare cases ischaemic stroke has been reported after methylphenidate intake in children. We report the case of a 63-year-old female who was treated with methylphenidate due to hyperactivity and suffered from multiple ischaemic strokes. We consider drug-induced cerebral vasculitis as the most likely cause of recurrent ischaemic strokes in the absence of any pathological findings during the diagnostic work-up. We conclude that methylphenidate mediated vasculitis should be considered in patients with neurological symptoms and a history of methylphenidate therapy. This potential side-effect, though very rare, represents one more reason to be very restrictive in the use of methylphenidate.","[{'text': 'Cerebral vasculitis', 'type': 'Disease', 'start': 0, 'end': 19, 'mesh': 'D020293'}, {'text': 'methylphenidate', 'type': 'Chemical', 'start': 35, 'end': 50, 'mesh': 'D008774'}, {'text': 'Methylphenidate', 'type': 'Chemical', 'start': 86, 'end': 101, 'mesh': 'D008774'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 146, 'end': 157, 'mesh': 'D000661'}, {'text': 'Cerebral vasculitis', 'type': 'Disease', 'start': 159, 'end': 178, 'mesh': 'D020293'}, {'text': 'amphetamine abuse', 'type': 'Disease', 'start': 195, 'end': 212, 'mesh': 'D019969'}, {'text': 'ischaemic stroke', 'type': 'Disease', 'start': 251, 'end': 267, 'mesh': 'D002544'}, {'text': 'methylphenidate', 'type': 'Chemical', 'start': 292, 'end': 307, 'mesh': 'D008774'}, {'text': 'methylphenidate', 'type': 'Chemical', 'start': 392, 'end': 407, 'mesh': 'D008774'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 415, 'end': 428, 'mesh': 'D006948'}, {'text': 'ischaemic strokes', 'type': 'Disease', 'start': 456, 'end': 473, 'mesh': 'D002544'}, {'text': 'cerebral vasculitis', 'type': 'Disease', 'start': 500, 'end': 519, 'mesh': 'D020293'}, {'text': 'ischaemic strokes', 'type': 'Disease', 'start': 558, 'end': 575, 'mesh': 'D002544'}, {'text': 'methylphenidate', 'type': 'Chemical', 'start': 668, 'end': 683, 'mesh': 'D008774'}, {'text': 'vasculitis', 'type': 'Disease', 'start': 693, 'end': 703, 'mesh': 'D014657'}, {'text': 'methylphenidate', 'type': 'Chemical', 'start': 781, 'end': 796, 'mesh': 'D008774'}, {'text': 'methylphenidate', 'type': 'Chemical', 'start': 916, 'end': 931, 'mesh': 'D008774'}]"
+245,16858720,Cerebral haemorrhage induced by warfarin - the influence of drug-drug interactions.,"PURPOSE: To evaluate the frequency, severity and preventability of warfarin-induced cerebral haemorrhages due to warfarin and warfarin-drug interactions in patients living in the county of Osterg  tland, Sweden. METHODS: All patients with a diagnosed cerebral haemorrhage at three hospitals during the period 2000-2002 were identified. Medical records were studied retrospectively to evaluate whether warfarin and warfarin-drug interactions could have caused the cerebral haemorrhage. The proportion of possibly avoidable cases due to drug interactions was estimated. RESULTS: Among 593 patients with cerebral haemorrhage, 59 (10%) were assessed as related to warfarin treatment. This imply an incidence of 1.7/100,000 treatment years. Of the 59 cases, 26 (44%) had a fatal outcome, compared to 136 (25%) among the non-warfarin patients (p < 0.01). A warfarin-drug interaction could have contributed to the haemorrhage in 24 (41%) of the warfarin patients and in 7 of these (12%) the bleeding complication was considered being possible to avoid. CONCLUSIONS: Warfarin-induced cerebral haemorrhages are a major clinical problem with a high fatality rate. Almost half of the cases was related to a warfarin-drug interaction. A significant proportion of warfarin-related cerebral haemorrhages might have been prevented if greater caution had been taken when prescribing drugs known to interact with warfarin.","[{'text': 'Cerebral haemorrhage', 'type': 'Disease', 'start': 0, 'end': 20, 'mesh': 'D002543'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 32, 'end': 40, 'mesh': 'D014859'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 151, 'end': 159, 'mesh': 'D014859'}, {'text': 'cerebral haemorrhages', 'type': 'Disease', 'start': 168, 'end': 189, 'mesh': 'D002543'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 197, 'end': 205, 'mesh': 'D014859'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 210, 'end': 218, 'mesh': 'D014859'}, {'text': 'cerebral haemorrhage', 'type': 'Disease', 'start': 335, 'end': 355, 'mesh': 'D002543'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 485, 'end': 493, 'mesh': 'D014859'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 498, 'end': 506, 'mesh': 'D014859'}, {'text': 'cerebral haemorrhage', 'type': 'Disease', 'start': 547, 'end': 567, 'mesh': 'D002543'}, {'text': 'cerebral haemorrhage', 'type': 'Disease', 'start': 685, 'end': 705, 'mesh': 'D002543'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 744, 'end': 752, 'mesh': 'D014859'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 903, 'end': 911, 'mesh': 'D014859'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 935, 'end': 943, 'mesh': 'D014859'}, {'text': 'haemorrhage', 'type': 'Disease', 'start': 991, 'end': 1002, 'mesh': 'D006470'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 1022, 'end': 1030, 'mesh': 'D014859'}, {'text': 'bleeding', 'type': 'Disease', 'start': 1068, 'end': 1076, 'mesh': 'D006470'}, {'text': 'Warfarin', 'type': 'Chemical', 'start': 1143, 'end': 1151, 'mesh': 'D014859'}, {'text': 'cerebral haemorrhages', 'type': 'Disease', 'start': 1160, 'end': 1181, 'mesh': 'D002543'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 1280, 'end': 1288, 'mesh': 'D014859'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 1335, 'end': 1343, 'mesh': 'D014859'}, {'text': 'cerebral haemorrhages', 'type': 'Disease', 'start': 1352, 'end': 1373, 'mesh': 'D002543'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 1480, 'end': 1488, 'mesh': 'D014859'}]"
+246,17466854,Side effects of postoperative administration of methylprednisolone and gentamicin into the posterior sub-Tenon's space.,"PURPOSE: To assess the incidence of postoperative emetic side effects after the administration of methylprednisolone and gentamicin into the posterior sub-Tenon's space at the end of routine cataract surgery. SETTING: St. Luke's Hospital, Gwardamangia, Malta. METHODS: A double-blind double-armed prospective study comprised 40 patients who had uneventful sutureless phacoemulsification under sub-Tenon's local infiltration of 3 mL of plain lignocaine. At the end of the procedure, Group A (n = 20) had 20 mg/0.5 mL of methylprednisolone and 10 mg/0.5 mL of gentamicin injected into the posterior sub-Tenon's space and Group B (n = 20) had the same combination injected into the anterior sub-Tenon's space. Postoperatively, all patients were assessed for symptoms of nausea, vomiting, and headache. A chi-square test was used to assess the statistical significance of results. RESULTS: Sixty percent in Group A developed postoperative emetic symptoms, headache, or both; 1 patient in Group B developed symptoms. CONCLUSIONS: The administration of methylprednisolone and gentamicin in the posterior sub-Tenon's space was related to a high incidence of side effects including nausea, vomiting, and headache. All adverse effects were self-limiting.","[{'text': 'methylprednisolone', 'type': 'Chemical', 'start': 48, 'end': 66, 'mesh': 'D008775'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 71, 'end': 81, 'mesh': 'D005839'}, {'text': 'methylprednisolone', 'type': 'Chemical', 'start': 218, 'end': 236, 'mesh': 'D008775'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 241, 'end': 251, 'mesh': 'D005839'}, {'text': 'cataract', 'type': 'Disease', 'start': 311, 'end': 319, 'mesh': 'D002386'}, {'text': 'lignocaine', 'type': 'Chemical', 'start': 561, 'end': 571, 'mesh': 'D008012'}, {'text': 'methylprednisolone', 'type': 'Chemical', 'start': 639, 'end': 657, 'mesh': 'D008775'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 678, 'end': 688, 'mesh': 'D005839'}, {'text': 'nausea, vomiting', 'type': 'Disease', 'start': 887, 'end': 903, 'mesh': 'D020250'}, {'text': 'headache', 'type': 'Disease', 'start': 909, 'end': 917, 'mesh': 'D006261'}, {'text': 'postoperative emetic symptoms', 'type': 'Disease', 'start': 1041, 'end': 1070, 'mesh': 'D020250'}, {'text': 'headache', 'type': 'Disease', 'start': 1072, 'end': 1080, 'mesh': 'D006261'}, {'text': 'methylprednisolone', 'type': 'Chemical', 'start': 1167, 'end': 1185, 'mesh': 'D008775'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 1190, 'end': 1200, 'mesh': 'D005839'}, {'text': 'nausea, vomiting', 'type': 'Disease', 'start': 1294, 'end': 1310, 'mesh': 'D020250'}, {'text': 'headache', 'type': 'Disease', 'start': 1316, 'end': 1324, 'mesh': 'D006261'}]"
+247,17562951,Cardiac Angiography in Renally Impaired Patients (CARE) study: a randomized double-blind trial of contrast-induced nephropathy in patients with chronic kidney disease.,"BACKGROUND: No direct comparisons exist of the renal tolerability of the low-osmolality contrast medium iopamidol with that of the iso-osmolality contrast medium iodixanol in high-risk patients. METHODS AND RESULTS: The present study is a multicenter, randomized, double-blind comparison of iopamidol and iodixanol in patients with chronic kidney disease (estimated glomerular filtration rate, 20 to 59 mL/min) who underwent cardiac angiography or percutaneous coronary interventions. Serum creatinine (SCr) levels and estimated glomerular filtration rate were assessed at baseline and 2 to 5 days after receiving medications. The primary outcome was a postdose SCr increase > or = 0.5 mg/dL (44.2 micromol/L) over baseline. Secondary outcomes were a postdose SCr increase > or = 25%, a postdose estimated glomerular filtration rate decrease of > or = 25%, and the mean peak change in SCr. In 414 patients, contrast volume, presence of diabetes mellitus, use of N-acetylcysteine, mean baseline SCr, and estimated glomerular filtration rate were comparable in the 2 groups. SCr increases > or = 0.5 mg/dL occurred in 4.4% (9 of 204 patients) after iopamidol and 6.7% (14 of 210 patients) after iodixanol (P=0.39), whereas rates of SCr increases > or = 25% were 9.8% and 12.4%, respectively (P=0.44). In patients with diabetes, SCr increases > or = 0.5 mg/dL were 5.1% (4 of 78 patients) with iopamidol and 13.0% (12 of 92 patients) with iodixanol (P=0.11), whereas SCr increases > or = 25% were 10.3% and 15.2%, respectively (P=0.37). Mean post-SCr increases were significantly less with iopamidol (all patients: 0.07 versus 0.12 mg/dL, 6.2 versus 10.6 micromol/L, P=0.03; patients with diabetes: 0.07 versus 0.16 mg/dL, 6.2 versus 14.1 micromol/L, P=0.01). CONCLUSIONS: The rate of contrast-induced nephropathy, defined by multiple end points, is not statistically different after the intraarterial administration of iopamidol or iodixanol to high-risk patients, with or without diabetes mellitus. Any true difference between the agents is small and not likely to be clinically significant.","[{'text': 'nephropathy', 'type': 'Disease', 'start': 115, 'end': 126, 'mesh': 'D007674'}, {'text': 'chronic kidney disease', 'type': 'Disease', 'start': 144, 'end': 166, 'mesh': 'D051436'}, {'text': 'contrast medium', 'type': 'Chemical', 'start': 256, 'end': 271, 'mesh': 'D003287'}, {'text': 'iopamidol', 'type': 'Chemical', 'start': 272, 'end': 281, 'mesh': 'D007479'}, {'text': 'contrast medium', 'type': 'Chemical', 'start': 314, 'end': 329, 'mesh': 'D003287'}, {'text': 'iodixanol', 'type': 'Chemical', 'start': 330, 'end': 339, 'mesh': 'C044834'}, {'text': 'iopamidol', 'type': 'Chemical', 'start': 459, 'end': 468, 'mesh': 'D007479'}, {'text': 'iodixanol', 'type': 'Chemical', 'start': 473, 'end': 482, 'mesh': 'C044834'}, {'text': 'chronic kidney disease', 'type': 'Disease', 'start': 500, 'end': 522, 'mesh': 'D051436'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 659, 'end': 669, 'mesh': 'D003404'}, {'text': 'diabetes mellitus', 'type': 'Disease', 'start': 1104, 'end': 1121, 'mesh': 'D003920'}, {'text': 'N-acetylcysteine', 'type': 'Chemical', 'start': 1130, 'end': 1146, 'mesh': 'D000111'}, {'text': 'iopamidol', 'type': 'Chemical', 'start': 1315, 'end': 1324, 'mesh': 'D007479'}, {'text': 'iodixanol', 'type': 'Chemical', 'start': 1361, 'end': 1370, 'mesh': 'C044834'}, {'text': 'diabetes', 'type': 'Disease', 'start': 1484, 'end': 1492, 'mesh': 'D003920'}, {'text': 'iopamidol', 'type': 'Chemical', 'start': 1559, 'end': 1568, 'mesh': 'D007479'}, {'text': 'iodixanol', 'type': 'Chemical', 'start': 1604, 'end': 1613, 'mesh': 'C044834'}, {'text': 'iopamidol', 'type': 'Chemical', 'start': 1755, 'end': 1764, 'mesh': 'D007479'}, {'text': 'diabetes', 'type': 'Disease', 'start': 1854, 'end': 1862, 'mesh': 'D003920'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1967, 'end': 1978, 'mesh': 'D007674'}, {'text': 'iopamidol', 'type': 'Chemical', 'start': 2085, 'end': 2094, 'mesh': 'D007479'}, {'text': 'iodixanol', 'type': 'Chemical', 'start': 2098, 'end': 2107, 'mesh': 'C044834'}, {'text': 'diabetes mellitus', 'type': 'Disease', 'start': 2147, 'end': 2164, 'mesh': 'D003920'}]"
+248,17600377,"A novel compound, maltolyl p-coumarate, attenuates cognitive deficits and shows neuroprotective effects in vitro and in vivo dementia models.","To develop a novel and effective drug that could enhance cognitive function and neuroprotection, we newly synthesized maltolyl p-coumarate by the esterification of maltol and p-coumaric acid. In the present study, we investigated whether maltolyl p-coumarate could improve cognitive decline in scopolamine-injected rats and in amyloid beta peptide(1-42)-infused rats. Maltolyl p-coumarate was found to attenuate cognitive deficits in both rat models using passive avoidance test and to reduce apoptotic cell death observed in the hippocampus of the amyloid beta peptide(1-42)-infused rats. We also examined the neuroprotective effects of maltolyl p-coumarate in vitro using SH-SY5Y cells. Cells were pretreated with maltolyl p-coumarate, before exposed to amyloid beta peptide(1-42), glutamate or H2O2. We found that maltolyl p-coumarate significantly decreased apoptotic cell death and reduced reactive oxygen species, cytochrome c release, and caspase 3 activation. Taking these in vitro and in vivo results together, our study suggests that maltolyl p-coumarate is a potentially effective candidate against Alzheimer's disease that is characterized by wide spread neuronal death and progressive decline of cognitive function.","[{'text': 'maltolyl p-coumarate', 'type': 'Chemical', 'start': 18, 'end': 38, 'mesh': 'C524754'}, {'text': 'cognitive deficits', 'type': 'Disease', 'start': 51, 'end': 69, 'mesh': 'D003072'}, {'text': 'dementia', 'type': 'Disease', 'start': 125, 'end': 133, 'mesh': 'D003704'}, {'text': 'maltolyl p-coumarate', 'type': 'Chemical', 'start': 260, 'end': 280, 'mesh': 'C524754'}, {'text': 'maltol', 'type': 'Chemical', 'start': 306, 'end': 312, 'mesh': 'C008316'}, {'text': 'p-coumaric acid', 'type': 'Chemical', 'start': 317, 'end': 332, 'mesh': 'C032171'}, {'text': 'maltolyl p-coumarate', 'type': 'Chemical', 'start': 380, 'end': 400, 'mesh': 'C524754'}, {'text': 'cognitive decline', 'type': 'Disease', 'start': 415, 'end': 432, 'mesh': 'D003072'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 436, 'end': 447, 'mesh': 'D012601'}, {'text': 'amyloid beta peptide(1-42)', 'type': 'Chemical', 'start': 469, 'end': 495, 'mesh': 'C544092'}, {'text': 'Maltolyl p-coumarate', 'type': 'Chemical', 'start': 510, 'end': 530, 'mesh': 'C524754'}, {'text': 'cognitive deficits', 'type': 'Disease', 'start': 554, 'end': 572, 'mesh': 'D003072'}, {'text': 'amyloid beta peptide(1-42)', 'type': 'Chemical', 'start': 691, 'end': 717, 'mesh': 'C544092'}, {'text': 'maltolyl p-coumarate', 'type': 'Chemical', 'start': 780, 'end': 800, 'mesh': 'C524754'}, {'text': 'maltolyl p-coumarate', 'type': 'Chemical', 'start': 858, 'end': 878, 'mesh': 'C524754'}, {'text': 'amyloid beta peptide(1-42)', 'type': 'Chemical', 'start': 898, 'end': 924, 'mesh': 'C544092'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 926, 'end': 935, 'mesh': 'D018698'}, {'text': 'H2O2', 'type': 'Chemical', 'start': 939, 'end': 943, 'mesh': 'D006861'}, {'text': 'maltolyl p-coumarate', 'type': 'Chemical', 'start': 959, 'end': 979, 'mesh': 'C524754'}, {'text': 'maltolyl p-coumarate', 'type': 'Chemical', 'start': 1186, 'end': 1206, 'mesh': 'C524754'}, {'text': ""Alzheimer's disease"", 'type': 'Disease', 'start': 1252, 'end': 1271, 'mesh': 'D000544'}, {'text': 'neuronal death', 'type': 'Disease', 'start': 1309, 'end': 1323, 'mesh': 'D009410'}, {'text': 'decline of cognitive function', 'type': 'Disease', 'start': 1340, 'end': 1369, 'mesh': 'D003072'}]"
+249,17639754,Interaction between warfarin and levofloxacin: case series.,"Warfarin is the most widely used oral anticoagulant and is indicated for many clinical conditions. Levofloxacin, a fluoroquinolone, is one of the most commonly prescribed antibiotics in clinical practice and is effective against Gram-positive, Gram-negative, and atypical bacteria. While small prospective studies have not revealed any significant drug-drug interaction between warfarin and levofloxacin, several case reports have indicated that levofloxacin may significantly potentiate the anticoagulation effect of warfarin. We report 3 cases of serious bleeding complications that appear to be the result of the interaction between warfarin and levofloxacin. Physicians should be aware of this potential interaction and use caution when prescribing levofloxacin to patients taking warfarin.","[{'text': 'warfarin', 'type': 'Chemical', 'start': 20, 'end': 28, 'mesh': 'D014859'}, {'text': 'levofloxacin', 'type': 'Chemical', 'start': 33, 'end': 45, 'mesh': 'D064704'}, {'text': 'Warfarin', 'type': 'Chemical', 'start': 60, 'end': 68, 'mesh': 'D014859'}, {'text': 'Levofloxacin', 'type': 'Chemical', 'start': 159, 'end': 171, 'mesh': 'D064704'}, {'text': 'fluoroquinolone', 'type': 'Chemical', 'start': 175, 'end': 190, 'mesh': 'D024841'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 438, 'end': 446, 'mesh': 'D014859'}, {'text': 'levofloxacin', 'type': 'Chemical', 'start': 451, 'end': 463, 'mesh': 'D064704'}, {'text': 'levofloxacin', 'type': 'Chemical', 'start': 506, 'end': 518, 'mesh': 'D064704'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 578, 'end': 586, 'mesh': 'D014859'}, {'text': 'bleeding', 'type': 'Disease', 'start': 617, 'end': 625, 'mesh': 'D006470'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 696, 'end': 704, 'mesh': 'D014859'}, {'text': 'levofloxacin', 'type': 'Chemical', 'start': 709, 'end': 721, 'mesh': 'D064704'}, {'text': 'levofloxacin', 'type': 'Chemical', 'start': 813, 'end': 825, 'mesh': 'D064704'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 845, 'end': 853, 'mesh': 'D014859'}]"
+250,17854040,Mutations associated with lamivudine-resistance in therapy-na  ve hepatitis B virus (HBV) infected patients with and without HIV co-infection: implications for antiretroviral therapy in HBV and HIV co-infected South African patients.,"This was an exploratory study to investigate lamivudine-resistant hepatitis B virus (HBV) strains in selected lamivudine-na  ve HBV carriers with and without human immunodeficiency virus (HIV) co-infection in South African patients. Thirty-five lamivudine-na  ve HBV infected patients with or without HIV co-infection were studied: 15 chronic HBV mono-infected patients and 20 HBV-HIV co-infected patients. The latter group was further sub-divided into 13 occult HBV (HBsAg-negative) and 7 overt HBV (HBsAg- positive) patients. HBsAg, anti-HBs, anti-HBc, and anti-HIV 1/2 were determined as part of routine diagnosis using Axsym assays (Abbott Laboratories, North Chicago, IL). Serum samples were PCR amplified with HBV reverse transcriptase (RT) primers, followed by direct sequencing across the tyrosine-methionine-aspartate-aspartate (YMDD) motif of the major catalytic region in the C domain of the HBV RT enzyme. HBV viral load was performed with Amplicor HBV Monitor test v2.0 (Roche Diagnostics, Penzberg, Germany). HBV lamivudine-resistant strains were detected in 3 of 15 mono-infected chronic hepatitis B patients and 10 of 20 HBV-HIV co-infected patients. To the best of our knowledge, this constitutes the first report of HBV lamivudine-resistant strains in therapy-na  ve HBV-HIV co-infected patients. The HBV viral loads for mono-infected and co-infected patients ranged from 3.32 x 10(2) to 3.82 x 10(7) and <200 to 4.40 x 10(3) copies/ml, respectively. It remains to be seen whether such pre-existing antiviral mutations could result in widespread emergence of HBV resistant strains when lamivudine-containing highly active antiretroviral (ARV) treatment (HAART) regimens become widely applied in South Africa, as this is likely to have potential implications in the management of HBV-HIV co-infected patients.","[{'text': 'lamivudine', 'type': 'Chemical', 'start': 26, 'end': 36, 'mesh': 'D019259'}, {'text': 'na', 'type': 'Chemical', 'start': 59, 'end': 61, 'mesh': 'D012964'}, {'text': 'hepatitis B virus (HBV) infected', 'type': 'Disease', 'start': 66, 'end': 98, 'mesh': 'D006509'}, {'text': 'HIV co-infection', 'type': 'Disease', 'start': 125, 'end': 141, 'mesh': 'D015658'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 279, 'end': 289, 'mesh': 'D019259'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 300, 'end': 311, 'mesh': 'D006509'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 344, 'end': 354, 'mesh': 'D019259'}, {'text': 'na', 'type': 'Chemical', 'start': 355, 'end': 357, 'mesh': 'D012964'}, {'text': 'human immunodeficiency virus (HIV) co-infection', 'type': 'Disease', 'start': 392, 'end': 439, 'mesh': 'D015658'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 479, 'end': 489, 'mesh': 'D019259'}, {'text': 'na', 'type': 'Chemical', 'start': 490, 'end': 492, 'mesh': 'D012964'}, {'text': 'HBV infected', 'type': 'Disease', 'start': 497, 'end': 509, 'mesh': 'D006509'}, {'text': 'HIV co-infection', 'type': 'Disease', 'start': 535, 'end': 551, 'mesh': 'D015658'}, {'text': 'HBV mono-infected', 'type': 'Disease', 'start': 577, 'end': 594, 'mesh': 'D006509'}, {'text': 'HBsAg', 'type': 'Chemical', 'start': 702, 'end': 707, 'mesh': 'D006514'}, {'text': 'HBsAg', 'type': 'Chemical', 'start': 735, 'end': 740, 'mesh': 'D006514'}, {'text': 'HBsAg', 'type': 'Chemical', 'start': 762, 'end': 767, 'mesh': 'D006514'}, {'text': 'tyrosine', 'type': 'Chemical', 'start': 1031, 'end': 1039, 'mesh': 'D014443'}, {'text': 'methionine', 'type': 'Chemical', 'start': 1040, 'end': 1050, 'mesh': 'D008715'}, {'text': 'aspartate', 'type': 'Chemical', 'start': 1051, 'end': 1060, 'mesh': 'D001224'}, {'text': 'aspartate', 'type': 'Chemical', 'start': 1061, 'end': 1070, 'mesh': 'D001224'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 1261, 'end': 1271, 'mesh': 'D019259'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 1337, 'end': 1348, 'mesh': 'D006509'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 1472, 'end': 1482, 'mesh': 'D019259'}, {'text': 'na', 'type': 'Chemical', 'start': 1512, 'end': 1514, 'mesh': 'D012964'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 1838, 'end': 1848, 'mesh': 'D019259'}]"
+251,18221780,Sex differences in NMDA antagonist enhancement of morphine antihyperalgesia in a capsaicin model of persistent pain: comparisons to two models of acute pain.,"In acute pain models, N-methyl-D-aspartate (NMDA) antagonists enhance the antinociceptive effects of morphine to a greater extent in males than females. The purpose of this investigation was to extend these findings to a persistent pain model which could be distinguished from acute pain models on the basis of the nociceptive fibers activated, neurochemical substrates, and duration of the nociceptive stimulus. To this end, persistent hyperalgesia was induced by administration of capsaicin in the tail of gonadally intact F344 rats, following which the tail was immersed in a mildly noxious thermal stimulus, and tail-withdrawal latencies measured. For comparison, tests were conducted in two acute pain models, the hotplate and warm water tail-withdrawal procedures. In males, the non-competitive NMDA antagonist dextromethorphan enhanced the antihyperalgesic effect of low to moderate doses of morphine in a dose-and time-dependent manner. Across the doses and pretreatment times examined, enhancement was not observed in females. Enhancement of morphine antinociception by dextromethorphan was seen in both males and females in the acute pain models, with the magnitude of this effect being greater in males. These findings demonstrate a sexually-dimorphic interaction between NMDA antagonists and morphine in a persistent pain model that can be distinguished from those observed in acute pain models.","[{'text': 'NMDA', 'type': 'Chemical', 'start': 19, 'end': 23, 'mesh': 'D016202'}, {'text': 'morphine', 'type': 'Chemical', 'start': 50, 'end': 58, 'mesh': 'D009020'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 81, 'end': 90, 'mesh': 'D002211'}, {'text': 'pain', 'type': 'Disease', 'start': 111, 'end': 115, 'mesh': 'D010146'}, {'text': 'acute pain', 'type': 'Disease', 'start': 146, 'end': 156, 'mesh': 'D059787'}, {'text': 'acute pain', 'type': 'Disease', 'start': 161, 'end': 171, 'mesh': 'D059787'}, {'text': 'N-methyl-D-aspartate', 'type': 'Chemical', 'start': 180, 'end': 200, 'mesh': 'D016202'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 202, 'end': 206, 'mesh': 'D016202'}, {'text': 'morphine', 'type': 'Chemical', 'start': 259, 'end': 267, 'mesh': 'D009020'}, {'text': 'pain', 'type': 'Disease', 'start': 390, 'end': 394, 'mesh': 'D010146'}, {'text': 'acute pain', 'type': 'Disease', 'start': 435, 'end': 445, 'mesh': 'D059787'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 595, 'end': 607, 'mesh': 'D006930'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 641, 'end': 650, 'mesh': 'D002211'}, {'text': 'acute pain', 'type': 'Disease', 'start': 854, 'end': 864, 'mesh': 'D059787'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 959, 'end': 963, 'mesh': 'D016202'}, {'text': 'dextromethorphan', 'type': 'Chemical', 'start': 975, 'end': 991, 'mesh': 'D003915'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1057, 'end': 1065, 'mesh': 'D009020'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1209, 'end': 1217, 'mesh': 'D009020'}, {'text': 'dextromethorphan', 'type': 'Chemical', 'start': 1237, 'end': 1253, 'mesh': 'D003915'}, {'text': 'acute pain', 'type': 'Disease', 'start': 1296, 'end': 1306, 'mesh': 'D059787'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 1441, 'end': 1445, 'mesh': 'D016202'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1462, 'end': 1470, 'mesh': 'D009020'}, {'text': 'pain', 'type': 'Disease', 'start': 1487, 'end': 1491, 'mesh': 'D010146'}, {'text': 'acute pain', 'type': 'Disease', 'start': 1547, 'end': 1557, 'mesh': 'D059787'}]"
+252,18261172,Development of proteinuria after switch to sirolimus-based immunosuppression in long-term cardiac transplant patients.,"Calcineurin-inhibitor therapy can lead to renal dysfunction in heart transplantation patients. The novel immunosuppressive (IS) drug sirolmus (Srl) lacks nephrotoxic effects; however, proteinuria associated with Srl has been reported following renal transplantation. In cardiac transplantation, the incidence of proteinuria associated with Srl is unknown. In this study, long-term cardiac transplant patients were switched from cyclosporine to Srl-based IS. Concomitant IS consisted of mycophenolate mofetil +/- steroids. Proteinuria increased significantly from a median of 0.13 g/day (range 0-5.7) preswitch to 0.23 g/day (0-9.88) at 24 months postswitch (p = 0.0024). Before the switch, 11.5% of patients had high-grade proteinuria (>1.0 g/day); this increased to 22.9% postswitch (p = 0.006). ACE inhibitor and angiotensin-releasing blocker (ARB) therapy reduced proteinuria development. Patients without proteinuria had increased renal function (median 42.5 vs. 64.1, p = 0.25), whereas patients who developed high-grade proteinuria showed decreased renal function at the end of follow-up (median 39.6 vs. 29.2, p = 0.125). Thus, proteinuria may develop in cardiac transplant patients after switch to Srl, which may have an adverse effect on renal function in these patients. Srl should be used with ACEi/ARB therapy and patients monitored for proteinuria and increased renal dysfunction.","[{'text': 'proteinuria', 'type': 'Disease', 'start': 15, 'end': 26, 'mesh': 'D011507'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 43, 'end': 52, 'mesh': 'D020123'}, {'text': 'renal dysfunction', 'type': 'Disease', 'start': 161, 'end': 178, 'mesh': 'D007674'}, {'text': 'sirolmus', 'type': 'Chemical', 'start': 252, 'end': 260, 'mesh': 'D020123'}, {'text': 'Srl', 'type': 'Chemical', 'start': 262, 'end': 265, 'mesh': 'D020123'}, {'text': 'nephrotoxic', 'type': 'Disease', 'start': 273, 'end': 284, 'mesh': 'D007674'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 303, 'end': 314, 'mesh': 'D011507'}, {'text': 'Srl', 'type': 'Chemical', 'start': 331, 'end': 334, 'mesh': 'D020123'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 431, 'end': 442, 'mesh': 'D011507'}, {'text': 'Srl', 'type': 'Chemical', 'start': 459, 'end': 462, 'mesh': 'D020123'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 547, 'end': 559, 'mesh': 'D016572'}, {'text': 'Srl', 'type': 'Chemical', 'start': 563, 'end': 566, 'mesh': 'D020123'}, {'text': 'mycophenolate mofetil', 'type': 'Chemical', 'start': 605, 'end': 626, 'mesh': 'C063008'}, {'text': 'steroids', 'type': 'Chemical', 'start': 631, 'end': 639, 'mesh': 'D013256'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 842, 'end': 853, 'mesh': 'D011507'}, {'text': 'ACE inhibitor', 'type': 'Chemical', 'start': 916, 'end': 929, 'mesh': 'D000806'}, {'text': 'angiotensin-releasing blocker', 'type': 'Chemical', 'start': 934, 'end': 963, 'mesh': 'D057911'}, {'text': 'ARB', 'type': 'Chemical', 'start': 965, 'end': 968, 'mesh': 'D057911'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 986, 'end': 997, 'mesh': 'D011507'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1028, 'end': 1039, 'mesh': 'D011507'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1145, 'end': 1156, 'mesh': 'D011507'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1254, 'end': 1265, 'mesh': 'D011507'}, {'text': 'Srl', 'type': 'Chemical', 'start': 1325, 'end': 1328, 'mesh': 'D020123'}, {'text': 'Srl', 'type': 'Chemical', 'start': 1400, 'end': 1403, 'mesh': 'D020123'}, {'text': 'ACEi', 'type': 'Chemical', 'start': 1424, 'end': 1428, 'mesh': 'D000806'}, {'text': 'ARB', 'type': 'Chemical', 'start': 1429, 'end': 1432, 'mesh': 'D057911'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1468, 'end': 1479, 'mesh': 'D011507'}, {'text': 'renal dysfunction', 'type': 'Disease', 'start': 1494, 'end': 1511, 'mesh': 'D007674'}]"
+253,18329269,Synthesis of N-pyrimidinyl-2-phenoxyacetamides as adenosine A2A receptor antagonists.,"A series of N-pyrimidinyl-2-phenoxyacetamide adenosine A(2A) antagonists is described. SAR studies led to compound 14 with excellent potency (K(i) = 0.4 nM), selectivity (A(1)/A(2A) > 100), and efficacy (MED 10 mg/kg p.o.) in the rat haloperidol-induced catalepsy model for Parkinson's disease.","[{'text': 'N-pyrimidinyl-2-phenoxyacetamides', 'type': 'Chemical', 'start': 13, 'end': 46, 'mesh': 'D010642'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 50, 'end': 59, 'mesh': 'D000241'}, {'text': 'N-pyrimidinyl-2-phenoxyacetamide', 'type': 'Chemical', 'start': 98, 'end': 130, 'mesh': 'D010642'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 131, 'end': 140, 'mesh': 'D000241'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 320, 'end': 331, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 340, 'end': 349, 'mesh': 'D002375'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 360, 'end': 379, 'mesh': 'D010300'}]"
+254,18410508,Methamphetamine-induced neurotoxicity and microglial activation are not mediated by fractalkine receptor signaling.,"Methamphetamine (METH) damages dopamine (DA) nerve endings by a process that has been linked to microglial activation but the signaling pathways that mediate this response have not yet been delineated. Cardona et al. [Nat. Neurosci. 9 (2006), 917] recently identified the microglial-specific fractalkine receptor (CX3CR1) as an important mediator of MPTP-induced neurodegeneration of DA neurons. Because the CNS damage caused by METH and MPTP is highly selective for the DA neuronal system in mouse models of neurotoxicity, we hypothesized that the CX3CR1 plays a role in METH-induced neurotoxicity and microglial activation. Mice in which the CX3CR1 gene has been deleted and replaced with a cDNA encoding enhanced green fluorescent protein (eGFP) were treated with METH and examined for striatal neurotoxicity. METH depleted DA, caused microglial activation, and increased body temperature in CX3CR1 knockout mice to the same extent and over the same time course seen in wild-type controls. The effects of METH in CX3CR1 knockout mice were not gender-dependent and did not extend beyond the striatum. Striatal microglia expressing eGFP constitutively show morphological changes after METH that are characteristic of activation. This response was restricted to the striatum and contrasted sharply with unresponsive eGFP-microglia in surrounding brain areas that are not damaged by METH. We conclude from these studies that CX3CR1 signaling does not modulate METH neurotoxicity or microglial activation. Furthermore, it appears that striatal-resident microglia respond to METH with an activation cascade and then return to a surveying state without undergoing apoptosis or migration.","[{'text': 'Methamphetamine', 'type': 'Chemical', 'start': 0, 'end': 15, 'mesh': 'D008694'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 24, 'end': 37, 'mesh': 'D020258'}, {'text': 'Methamphetamine', 'type': 'Chemical', 'start': 116, 'end': 131, 'mesh': 'D008694'}, {'text': 'METH', 'type': 'Chemical', 'start': 133, 'end': 137, 'mesh': 'D008694'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 147, 'end': 155, 'mesh': 'D004298'}, {'text': 'DA', 'type': 'Chemical', 'start': 157, 'end': 159, 'mesh': 'D004298'}, {'text': 'MPTP', 'type': 'Chemical', 'start': 466, 'end': 470, 'mesh': 'D015632'}, {'text': 'neurodegeneration', 'type': 'Disease', 'start': 479, 'end': 496, 'mesh': 'D009422'}, {'text': 'DA', 'type': 'Chemical', 'start': 500, 'end': 502, 'mesh': 'D004298'}, {'text': 'CNS damage', 'type': 'Disease', 'start': 524, 'end': 534, 'mesh': 'D009422'}, {'text': 'METH', 'type': 'Chemical', 'start': 545, 'end': 549, 'mesh': 'D008694'}, {'text': 'MPTP', 'type': 'Chemical', 'start': 554, 'end': 558, 'mesh': 'D015632'}, {'text': 'DA', 'type': 'Chemical', 'start': 587, 'end': 589, 'mesh': 'D004298'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 625, 'end': 638, 'mesh': 'D020258'}, {'text': 'METH', 'type': 'Chemical', 'start': 688, 'end': 692, 'mesh': 'D008694'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 701, 'end': 714, 'mesh': 'D020258'}, {'text': 'METH', 'type': 'Chemical', 'start': 883, 'end': 887, 'mesh': 'D008694'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 914, 'end': 927, 'mesh': 'D020258'}, {'text': 'METH', 'type': 'Chemical', 'start': 929, 'end': 933, 'mesh': 'D008694'}, {'text': 'DA', 'type': 'Chemical', 'start': 943, 'end': 945, 'mesh': 'D004298'}, {'text': 'METH', 'type': 'Chemical', 'start': 1124, 'end': 1128, 'mesh': 'D008694'}, {'text': 'METH', 'type': 'Chemical', 'start': 1302, 'end': 1306, 'mesh': 'D008694'}, {'text': 'METH', 'type': 'Chemical', 'start': 1498, 'end': 1502, 'mesh': 'D008694'}, {'text': 'METH', 'type': 'Chemical', 'start': 1575, 'end': 1579, 'mesh': 'D008694'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 1580, 'end': 1593, 'mesh': 'D020258'}, {'text': 'METH', 'type': 'Chemical', 'start': 1688, 'end': 1692, 'mesh': 'D008694'}]"
+255,18503483,Recovery of tacrolimus-associated brachial neuritis after conversion to everolimus in a pediatric renal transplant recipient--case report and review of the literature.,"TAC has been shown to be a potent immunosuppressive agent for solid organ transplantation in pediatrics. Neurotoxicity is a potentially serious toxic effect. It is characterized by encephalopathy, headaches, seizures, or neurological deficits. Here, we describe an eight-and-a-half-yr-old male renal transplant recipient with right BN. MRI demonstrated hyperintense T2 signals in the cervical cord and right brachial plexus roots indicative of both myelitis and right brachial plexitis. Symptoms persisted for three months despite TAC dose reduction, administration of IVIG and four doses of methylprednisolone pulse therapy. Improvement and eventually full recovery only occurred after TAC was completely discontinued and successfully replaced by everolimus.","[{'text': 'tacrolimus', 'type': 'Chemical', 'start': 12, 'end': 22, 'mesh': 'D016559'}, {'text': 'brachial neuritis', 'type': 'Disease', 'start': 34, 'end': 51, 'mesh': 'D020968'}, {'text': 'everolimus', 'type': 'Chemical', 'start': 72, 'end': 82, 'mesh': 'C107135'}, {'text': 'TAC', 'type': 'Chemical', 'start': 168, 'end': 171, 'mesh': 'D016559'}, {'text': 'Neurotoxicity', 'type': 'Disease', 'start': 273, 'end': 286, 'mesh': 'D020258'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 349, 'end': 363, 'mesh': 'D001927'}, {'text': 'headaches', 'type': 'Disease', 'start': 365, 'end': 374, 'mesh': 'D006261'}, {'text': 'seizures', 'type': 'Disease', 'start': 376, 'end': 384, 'mesh': 'D012640'}, {'text': 'neurological deficits', 'type': 'Disease', 'start': 389, 'end': 410, 'mesh': 'D009461'}, {'text': 'myelitis', 'type': 'Disease', 'start': 617, 'end': 625, 'mesh': 'D009187'}, {'text': 'brachial plexitis', 'type': 'Disease', 'start': 636, 'end': 653, 'mesh': 'D020968'}, {'text': 'TAC', 'type': 'Chemical', 'start': 699, 'end': 702, 'mesh': 'D016559'}, {'text': 'methylprednisolone', 'type': 'Chemical', 'start': 760, 'end': 778, 'mesh': 'D008775'}, {'text': 'TAC', 'type': 'Chemical', 'start': 855, 'end': 858, 'mesh': 'D016559'}, {'text': 'everolimus', 'type': 'Chemical', 'start': 916, 'end': 926, 'mesh': 'C107135'}]"
+256,18560792,Valvular heart disease in patients with Parkinson's disease treated with pergolide. Course following treatment modifications.,"Valvular heart abnormalities have been reported in patients with Parkinson's disease (PD) treated with pergolide. However, the incidence and severity of these abnormalities vary from study to study and their course after drug withdrawal has not been systematically assessed. OBJECTIVES: To estimate the frequency and severity of valvular heart abnormality and its possible reversibility after drug withdrawal in a case-control study. METHODS: All PD patients in the Amiens area treated with pergolide were invited to attend a cardiologic assessment including transthoracic echocardiography. Thirty PD patients participated in the study. A second echocardiography was performed (median interval: 13 months) after pergolide withdrawal (n=10 patients). Controls were age- and sex-matched non-PD patients referred to the cardiology department. RESULTS: Compared to controls, aortic regurgitation (OR: 3.1; 95% IC: 1.1-8.8) and mitral regurgitation (OR: 10.7; 95% IC: 2.1-53) were more frequent in PD patients (tricuspid: NS). The number of affected valves (n=2.4+/-0.7) and the sum of regurgitation grades (n=2.8+/-1.09) were higher (p=0.008 and p=0.006, respectively) in the pergolide group. Severity of regurgitation was not correlated with pergolide cumulative dose. A restrictive pattern of valvular regurgitation, suggestive of the role of pergolide, was observed in 12/30 (40%) patients including two with heart failure. Pergolide was discontinued in 10 patients with valvular heart disease, resulting in a lower regurgitation grade (p=0.01) at the second transthoracic echocardiography and the two patients with heart failure returned to nearly normal clinical examination. This study supports the high frequency of restrictive valve regurgitation in PD patients treated with pergolide and reveals that a significant improvement is usual when the treatment is converted to non-ergot dopamine agonists.","[{'text': 'Valvular heart disease', 'type': 'Disease', 'start': 0, 'end': 22, 'mesh': 'D006349'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 40, 'end': 59, 'mesh': 'D010300'}, {'text': 'pergolide', 'type': 'Chemical', 'start': 73, 'end': 82, 'mesh': 'D010479'}, {'text': 'Valvular heart abnormalities', 'type': 'Disease', 'start': 126, 'end': 154, 'mesh': 'D006349'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 191, 'end': 210, 'mesh': 'D010300'}, {'text': 'PD', 'type': 'Disease', 'start': 212, 'end': 214, 'mesh': 'D010300'}, {'text': 'pergolide', 'type': 'Chemical', 'start': 229, 'end': 238, 'mesh': 'D010479'}, {'text': 'valvular heart abnormality', 'type': 'Disease', 'start': 455, 'end': 481, 'mesh': 'D006349'}, {'text': 'PD', 'type': 'Disease', 'start': 573, 'end': 575, 'mesh': 'D010300'}, {'text': 'pergolide', 'type': 'Chemical', 'start': 617, 'end': 626, 'mesh': 'D010479'}, {'text': 'PD', 'type': 'Disease', 'start': 724, 'end': 726, 'mesh': 'D010300'}, {'text': 'pergolide', 'type': 'Chemical', 'start': 838, 'end': 847, 'mesh': 'D010479'}, {'text': 'PD', 'type': 'Disease', 'start': 915, 'end': 917, 'mesh': 'D010300'}, {'text': 'aortic regurgitation', 'type': 'Disease', 'start': 997, 'end': 1017, 'mesh': 'D001022'}, {'text': 'mitral regurgitation', 'type': 'Disease', 'start': 1049, 'end': 1069, 'mesh': 'D008944'}, {'text': 'PD', 'type': 'Disease', 'start': 1119, 'end': 1121, 'mesh': 'D010300'}, {'text': 'pergolide', 'type': 'Chemical', 'start': 1298, 'end': 1307, 'mesh': 'D010479'}, {'text': 'pergolide', 'type': 'Chemical', 'start': 1365, 'end': 1374, 'mesh': 'D010479'}, {'text': 'valvular regurgitation', 'type': 'Disease', 'start': 1417, 'end': 1439, 'mesh': 'D006349'}, {'text': 'pergolide', 'type': 'Chemical', 'start': 1467, 'end': 1476, 'mesh': 'D010479'}, {'text': 'heart failure', 'type': 'Disease', 'start': 1534, 'end': 1547, 'mesh': 'D006333'}, {'text': 'Pergolide', 'type': 'Chemical', 'start': 1549, 'end': 1558, 'mesh': 'D010479'}, {'text': 'valvular heart disease', 'type': 'Disease', 'start': 1596, 'end': 1618, 'mesh': 'D006349'}, {'text': 'heart failure', 'type': 'Disease', 'start': 1741, 'end': 1754, 'mesh': 'D006333'}, {'text': 'valve regurgitation', 'type': 'Disease', 'start': 1857, 'end': 1876, 'mesh': 'D006349'}, {'text': 'PD', 'type': 'Disease', 'start': 1880, 'end': 1882, 'mesh': 'D010300'}, {'text': 'pergolide', 'type': 'Chemical', 'start': 1905, 'end': 1914, 'mesh': 'D010479'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 2012, 'end': 2020, 'mesh': 'D004298'}]"
+257,18726058,Adverse effects of topical papaverine on auditory nerve function.,"BACKGROUND: Papaverine hydrochloride is a direct-acting vasodilator used to manage vasospasm during various neurosurgical operations. Transient cranial nerve dysfunction has been described in a few cases with topical papaverine. This study supports previous reports and provides neurophysiological evidence of an adverse effect on the auditory nerve. METHODS: We conducted a retrospective review of 70 consecutive microvascular decompression operations and studied those patients who received topical papaverine for vasospasm. Topical papaverine was used as a direct therapeutic action to manage vasospasm in a total of 11 patients. The timing of papaverine application and ongoing operative events was reviewed relative to changes in neurophysiological recordings. Brainstem auditory evoked potentials (BAEPs) were routinely used to monitor cochlear nerve function during these operations. FINDINGS: A temporal relationship was found between topical papaverine and BAEP changes leading to complete waveform loss. The average temporal delay between papaverine and the onset of an adverse BAEP change was 5 min. In 10 of 11 patients, BAEP waves II/III-V completely disappeared within 2 to 25 min after papaverine. Eight of these 10 patients had complete loss of BAEP waveforms within 10 min. One patient showed no recovery of later waves and a delayed profound sensorineural hearing loss. The average recovery time of BAEP waveforms to pre-papaverine baseline values was 39 min. CONCLUSIONS: Topical papaverine for the treatment of vasospasm was associated with the onset of a transient disturbance in neurophysiological function of the ascending auditory brainstem pathway. The complete disappearance of BAEP waveforms with a consistent temporal delay suggests a possible adverse effect on the proximal eighth nerve. Recommendations to avoid potential cranial nerve deficits from papaverine are provided.","[{'text': 'papaverine', 'type': 'Chemical', 'start': 27, 'end': 37, 'mesh': 'D010208'}, {'text': 'Papaverine hydrochloride', 'type': 'Chemical', 'start': 78, 'end': 102, 'mesh': 'D010208'}, {'text': 'vasospasm', 'type': 'Disease', 'start': 149, 'end': 158, 'mesh': 'D020301'}, {'text': 'cranial nerve dysfunction', 'type': 'Disease', 'start': 210, 'end': 235, 'mesh': 'D003389'}, {'text': 'papaverine', 'type': 'Chemical', 'start': 283, 'end': 293, 'mesh': 'D010208'}, {'text': 'papaverine', 'type': 'Chemical', 'start': 567, 'end': 577, 'mesh': 'D010208'}, {'text': 'vasospasm', 'type': 'Disease', 'start': 582, 'end': 591, 'mesh': 'D020301'}, {'text': 'papaverine', 'type': 'Chemical', 'start': 601, 'end': 611, 'mesh': 'D010208'}, {'text': 'vasospasm', 'type': 'Disease', 'start': 662, 'end': 671, 'mesh': 'D020301'}, {'text': 'papaverine', 'type': 'Chemical', 'start': 713, 'end': 723, 'mesh': 'D010208'}, {'text': 'papaverine', 'type': 'Chemical', 'start': 1017, 'end': 1027, 'mesh': 'D010208'}, {'text': 'papaverine', 'type': 'Chemical', 'start': 1115, 'end': 1125, 'mesh': 'D010208'}, {'text': 'papaverine', 'type': 'Chemical', 'start': 1267, 'end': 1277, 'mesh': 'D010208'}, {'text': 'sensorineural hearing loss', 'type': 'Disease', 'start': 1426, 'end': 1452, 'mesh': 'D006319'}, {'text': 'papaverine', 'type': 'Chemical', 'start': 1505, 'end': 1515, 'mesh': 'D010208'}, {'text': 'papaverine', 'type': 'Chemical', 'start': 1565, 'end': 1575, 'mesh': 'D010208'}, {'text': 'vasospasm', 'type': 'Disease', 'start': 1597, 'end': 1606, 'mesh': 'D020301'}, {'text': 'adverse effect on the proximal eighth nerve', 'type': 'Disease', 'start': 1838, 'end': 1881, 'mesh': 'D000160'}, {'text': 'cranial nerve deficits', 'type': 'Disease', 'start': 1918, 'end': 1940, 'mesh': 'D003389'}, {'text': 'papaverine', 'type': 'Chemical', 'start': 1946, 'end': 1956, 'mesh': 'D010208'}]"
+258,18754075,Massive proteinuria and acute renal failure after oral bisphosphonate (alendronate) administration in a patient with focal segmental glomerulosclerosis.,"A 61-year-old Japanese man with nephrotic syndrome due to focal segmental glomerulosclerosis was initially responding well to steroid therapy. The amount of daily urinary protein decreased from 15.6 to 2.8 g. Within 14 days of the oral bisphosphonate (alendronate sodium) administration, the amount of daily urinary protein increased rapidly up to 12.8 g with acute renal failure. After discontinuing the oral alendronate, the patient underwent six cycles of hemodialysis and four cycles of LDL apheresis. Urinary volume and serum creatinine levels recovered to the normal range, with urinary protein disappearing completely within 40 days. This report demonstrates that not only intravenous, but also oral bisphosphonates can aggravate proteinuria and acute renal failure.","[{'text': 'proteinuria', 'type': 'Disease', 'start': 8, 'end': 19, 'mesh': 'D011507'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 24, 'end': 43, 'mesh': 'D058186'}, {'text': 'bisphosphonate', 'type': 'Chemical', 'start': 55, 'end': 69, 'mesh': 'D004164'}, {'text': 'alendronate', 'type': 'Chemical', 'start': 71, 'end': 82, 'mesh': 'D019386'}, {'text': 'focal segmental glomerulosclerosis', 'type': 'Disease', 'start': 117, 'end': 151, 'mesh': 'D005923'}, {'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 185, 'end': 203, 'mesh': 'D009404'}, {'text': 'focal segmental glomerulosclerosis', 'type': 'Disease', 'start': 211, 'end': 245, 'mesh': 'D005923'}, {'text': 'steroid', 'type': 'Chemical', 'start': 279, 'end': 286, 'mesh': 'D013256'}, {'text': 'bisphosphonate', 'type': 'Chemical', 'start': 389, 'end': 403, 'mesh': 'D004164'}, {'text': 'alendronate sodium', 'type': 'Chemical', 'start': 405, 'end': 423, 'mesh': 'D019386'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 513, 'end': 532, 'mesh': 'D058186'}, {'text': 'alendronate', 'type': 'Chemical', 'start': 563, 'end': 574, 'mesh': 'D019386'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 684, 'end': 694, 'mesh': 'D003404'}, {'text': 'bisphosphonates', 'type': 'Chemical', 'start': 860, 'end': 875, 'mesh': 'D004164'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 890, 'end': 901, 'mesh': 'D011507'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 906, 'end': 925, 'mesh': 'D058186'}]"
+259,18768591,Serum- and glucocorticoid-inducible kinase 1 in doxorubicin-induced nephrotic syndrome.,"Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 mug/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)). Doxorubicin treatment resulted in heavy proteinuria (>100 mg protein/mg crea) in 15/44 of sgk1(+/+) and 15/44 of sgk1(-/-) mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1(+/+) mice. Urinary sodium excretion reached signficantly lower values in sgk1(+/+) mice (15 +/- 5 mumol/mg crea) than in sgk1(-/-) mice (35 +/- 5 mumol/mg crea) and was associated with a significantly higher body weight gain in sgk1(+/+) compared with sgk1(-/-) mice (+6.6 +/- 0.7 vs. +4.1 +/- 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1(-/-) mice than in sgk1(+/+) mice leading to uremia and a reduced median survival in sgk1(-/-) mice (29 vs. 40 days in sgk1(+/+) mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.","[{'text': 'doxorubicin', 'type': 'Chemical', 'start': 48, 'end': 59, 'mesh': 'D004317'}, {'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 68, 'end': 86, 'mesh': 'D009404'}, {'text': 'Doxorubicin', 'type': 'Chemical', 'start': 88, 'end': 99, 'mesh': 'D004317'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 108, 'end': 119, 'mesh': 'D007674'}, {'text': 'sodium', 'type': 'Chemical', 'start': 140, 'end': 146, 'mesh': 'D012964'}, {'text': 'volume retention', 'type': 'Disease', 'start': 172, 'end': 188, 'mesh': 'D016055'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 199, 'end': 207, 'mesh': 'D005355'}, {'text': 'aldosterone', 'type': 'Chemical', 'start': 213, 'end': 224, 'mesh': 'D000450'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 361, 'end': 369, 'mesh': 'D005355'}, {'text': 'volume retention', 'type': 'Disease', 'start': 484, 'end': 500, 'mesh': 'D016055'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 505, 'end': 513, 'mesh': 'D005355'}, {'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 521, 'end': 539, 'mesh': 'D009404'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 554, 'end': 565, 'mesh': 'D004317'}, {'text': 'Doxorubicin', 'type': 'Chemical', 'start': 706, 'end': 717, 'mesh': 'D004317'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 746, 'end': 757, 'mesh': 'D011507'}, {'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 852, 'end': 870, 'mesh': 'D009404'}, {'text': 'ascites', 'type': 'Disease', 'start': 876, 'end': 883, 'mesh': 'D001201'}, {'text': 'lipidemia', 'type': 'Disease', 'start': 885, 'end': 894, 'mesh': 'D006949'}, {'text': 'hypoalbuminemia', 'type': 'Disease', 'start': 900, 'end': 915, 'mesh': 'D034141'}, {'text': 'aldosterone', 'type': 'Chemical', 'start': 942, 'end': 953, 'mesh': 'D000450'}, {'text': 'nephrotic', 'type': 'Disease', 'start': 974, 'end': 983, 'mesh': 'D009404'}, {'text': 'sodium', 'type': 'Chemical', 'start': 1088, 'end': 1094, 'mesh': 'D012964'}, {'text': 'weight gain', 'type': 'Disease', 'start': 1282, 'end': 1293, 'mesh': 'D015430'}, {'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 1392, 'end': 1410, 'mesh': 'D009404'}, {'text': 'urea', 'type': 'Chemical', 'start': 1418, 'end': 1422, 'mesh': 'D014508'}, {'text': 'uremia', 'type': 'Disease', 'start': 1521, 'end': 1527, 'mesh': 'D014511'}, {'text': 'volume retention', 'type': 'Disease', 'start': 1674, 'end': 1690, 'mesh': 'D016055'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 1729, 'end': 1737, 'mesh': 'D005355'}, {'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 1758, 'end': 1776, 'mesh': 'D009404'}]"
+260,19299179,Severe and long lasting cholestasis after high-dose co-trimoxazole treatment for Pneumocystis pneumonia in HIV-infected patients--a report of two cases.,"Pneumocystis pneumonia (PCP), a common opportunistic infection in HIV-infected individuals, is generally treated with high doses of co-trimoxazole. However, treatment is often limited by adverse effects. Here, we report two cases of severely immunocompromised HIV-infected patients who developed severe intrahepatic cholestasis, and in one patient lesions mimicking liver abscess formation on radiologic exams, during co-trimoxazole treatment for PCP. Whereas patient 1 showed lesions of up to 1 cm readily detectable on magnetic resonance imaging under prolonged co-trimoxazole treatment, therapy of patient 2 was switched early.","[{'text': 'cholestasis', 'type': 'Disease', 'start': 24, 'end': 35, 'mesh': 'D002779'}, {'text': 'co-trimoxazole', 'type': 'Chemical', 'start': 52, 'end': 66, 'mesh': 'D015662'}, {'text': 'Pneumocystis pneumonia', 'type': 'Disease', 'start': 81, 'end': 103, 'mesh': 'D011020'}, {'text': 'HIV-infected', 'type': 'Disease', 'start': 107, 'end': 119, 'mesh': 'D015658'}, {'text': 'Pneumocystis pneumonia', 'type': 'Disease', 'start': 153, 'end': 175, 'mesh': 'D011020'}, {'text': 'PCP', 'type': 'Disease', 'start': 177, 'end': 180, 'mesh': 'D011020'}, {'text': 'opportunistic infection', 'type': 'Disease', 'start': 192, 'end': 215, 'mesh': 'D009894'}, {'text': 'HIV-infected', 'type': 'Disease', 'start': 219, 'end': 231, 'mesh': 'D015658'}, {'text': 'co-trimoxazole', 'type': 'Chemical', 'start': 285, 'end': 299, 'mesh': 'D015662'}, {'text': 'HIV-infected', 'type': 'Disease', 'start': 413, 'end': 425, 'mesh': 'D015658'}, {'text': 'intrahepatic cholestasis', 'type': 'Disease', 'start': 456, 'end': 480, 'mesh': 'D002780'}, {'text': 'liver abscess', 'type': 'Disease', 'start': 519, 'end': 532, 'mesh': 'D008100'}, {'text': 'co-trimoxazole', 'type': 'Chemical', 'start': 571, 'end': 585, 'mesh': 'D015662'}, {'text': 'PCP', 'type': 'Disease', 'start': 600, 'end': 603, 'mesh': 'D011020'}, {'text': 'co-trimoxazole', 'type': 'Chemical', 'start': 717, 'end': 731, 'mesh': 'D015662'}]"
+261,19356053,Clinically significant proteinuria following the administration of sirolimus to renal transplant recipients.,"BACKGROUND: Sirolimus is the latest immunosuppressive agent used to prevent rejection, and may have less nephrotoxicity than calcineurin inhibitor (CNI)-based regimens. To date there has been little documentation of clinically significant proteinuria linked with the use of sirolimus. We have encountered several patients who developed substantial proteinuria associated with sirolimus use. In each patient, the close temporal association between the commencement of sirolimus therapy and proteinuria implicated sirolimus as the most likely etiology of the proteinuria. METHODS: We analyzed the clinical and laboratory information available for all 119 patients transplanted at the Washington Hospital Center between 1999-2003 for whom sirolimus was a component of their immunosuppressant regimen. In these patients, the magnitude of proteinuria was assessed on morning urine samples by turbidometric measurement or random urine protein:creatinine ratios, an estimate of grams of proteinuria/day. Laboratory results were compared between prior, during and following sirolimus use. RESULTS: Twenty-eight patients (24%) developed increased proteinuria from baseline during their post-transplantation course. In 21 patients an alternative cause of proteinuria was either obvious or insufficient data was available to be conclusive. In 7 of the 28 patients there was a striking temporal association between the initiation of sirolimus and the development of nephrotic-range proteinuria. Proteinuria correlated most strongly with sirolimus therapy when compared to other demographic and clinical variables. In most patients, discontinuation of sirolimus resulted in a decrease, but not resolution, of proteinuria. CONCLUSIONS: Sirolimus induces or aggravates pre-existing proteinuria in an unpredictable subset of renal allograft recipients. Proteinuria may improve, but does not resolve, when sirolimus is withdrawn.","[{'text': 'proteinuria', 'type': 'Disease', 'start': 23, 'end': 34, 'mesh': 'D011507'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 67, 'end': 76, 'mesh': 'D020123'}, {'text': 'Sirolimus', 'type': 'Chemical', 'start': 121, 'end': 130, 'mesh': 'D020123'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 214, 'end': 228, 'mesh': 'D007674'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 348, 'end': 359, 'mesh': 'D011507'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 383, 'end': 392, 'mesh': 'D020123'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 457, 'end': 468, 'mesh': 'D011507'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 485, 'end': 494, 'mesh': 'D020123'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 576, 'end': 585, 'mesh': 'D020123'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 598, 'end': 609, 'mesh': 'D011507'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 621, 'end': 630, 'mesh': 'D020123'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 666, 'end': 677, 'mesh': 'D011507'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 845, 'end': 854, 'mesh': 'D020123'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 943, 'end': 954, 'mesh': 'D011507'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1046, 'end': 1056, 'mesh': 'D003404'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1089, 'end': 1100, 'mesh': 'D011507'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 1175, 'end': 1184, 'mesh': 'D020123'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1247, 'end': 1258, 'mesh': 'D011507'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1354, 'end': 1365, 'mesh': 'D011507'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 1530, 'end': 1539, 'mesh': 'D020123'}, {'text': 'nephrotic', 'type': 'Disease', 'start': 1563, 'end': 1572, 'mesh': 'D009404'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1579, 'end': 1590, 'mesh': 'D011507'}, {'text': 'Proteinuria', 'type': 'Disease', 'start': 1592, 'end': 1603, 'mesh': 'D011507'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 1634, 'end': 1643, 'mesh': 'D020123'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 1748, 'end': 1757, 'mesh': 'D020123'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1805, 'end': 1816, 'mesh': 'D011507'}, {'text': 'Sirolimus', 'type': 'Chemical', 'start': 1831, 'end': 1840, 'mesh': 'D020123'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1876, 'end': 1887, 'mesh': 'D011507'}, {'text': 'Proteinuria', 'type': 'Disease', 'start': 1946, 'end': 1957, 'mesh': 'D011507'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 1998, 'end': 2007, 'mesh': 'D020123'}]"
+262,19729346,Comparative cognitive and subjective side effects of immediate-release oxycodone in healthy middle-aged and older adults.,"This study measured the objective and subjective neurocognitive effects of a single 10-mg dose of immediate-release oxycodone in healthy, older (> 65 years), and middle-aged (35 to 55 years) adults who were not suffering from chronic or significant daily pain. Seventy-one participants completed 2 separate study days and were blind to medication condition (placebo, 10-mg oxycodone). Plasma oxycodone concentration peaked between 60 and 90 minutes postdose (P < .01) and pupil size, an indication of physiological effects of the medication, peaked at approximately 90 to 120 minutes postdose (P < .01). Significant declines in simple and sustained attention, working memory, and verbal memory were observed at 1 hour postdose compared to baseline for both age groups with a trend toward return to baseline by 5 hours postdose. For almost all cognitive measures, there were no medication by age-interaction effects, which indicates that the 2 age groups exhibited similar responses to the medication challenge. This study suggests that for healthy older adults who are not suffering from chronic pain, neurocognitive and pharmacodynamic changes in response to a 10-mg dose of immediate-release oxycodone are similar to those observed for middle-aged adults. PERSPECTIVE: Study findings indicate that the metabolism, neurocognitive effects, and physical side effects of oral oxycodone are similar for healthy middle-aged and older adults. Therefore, clinicians should not avoid prescribing oral opioids to older adults based on the belief that older adults are at higher risk for side effects than younger adults.","[{'text': 'oxycodone', 'type': 'Chemical', 'start': 71, 'end': 80, 'mesh': 'D010098'}, {'text': 'oxycodone', 'type': 'Chemical', 'start': 238, 'end': 247, 'mesh': 'D010098'}, {'text': 'pain', 'type': 'Disease', 'start': 377, 'end': 381, 'mesh': 'D010146'}, {'text': 'oxycodone', 'type': 'Chemical', 'start': 495, 'end': 504, 'mesh': 'D010098'}, {'text': 'oxycodone', 'type': 'Chemical', 'start': 514, 'end': 523, 'mesh': 'D010098'}, {'text': 'chronic pain', 'type': 'Disease', 'start': 1210, 'end': 1222, 'mesh': 'D059350'}, {'text': 'oxycodone', 'type': 'Chemical', 'start': 1316, 'end': 1325, 'mesh': 'D010098'}, {'text': 'oxycodone', 'type': 'Chemical', 'start': 1496, 'end': 1505, 'mesh': 'D010098'}]"
+263,20080983,Normalizing effects of modafinil on sleep in chronic cocaine users.,"OBJECTIVE: The purpose of the present study was to determine the effect of morning-dosed modafinil on sleep and daytime sleepiness in chronic cocaine users. METHOD: Twenty cocaine-dependent participants were randomly assigned to receive modafinil, 400 mg (N=10), or placebo (N=10) every morning at 7:30 a.m. for 16 days in an inpatient, double-blind randomized trial. Participants underwent polysomnographic sleep recordings on days 1 to 3, 7 to 9, and 14 to 16 (first, second, and third weeks of abstinence). The Multiple Sleep Latency Test was performed at 11:30 a.m., 2:00 p.m., and 4:30 p.m. on days 2, 8, and 15. For comparison of sleep architecture variables, 12 healthy comparison participants underwent a single night of experimental polysomnography that followed 1 night of accommodation polysomnography. RESULTS: Progressive abstinence from cocaine was associated with worsening of all measured polysomnographic sleep outcomes. Compared with placebo, modafinil decreased nighttime sleep latency and increased slow-wave sleep time in cocaine-dependent participants. The effect of modafinil interacted with the abstinence week and was associated with longer total sleep time and shorter REM sleep latency in the third week of abstinence. Comparison of slow-wave sleep time, total sleep time, and sleep latency in cocaine-dependent and healthy participants revealed a normalizing effect of modafinil in cocaine-dependent participants. Modafinil was associated with increased daytime sleep latency, as measured by the Multiple Sleep Latency Test, and a nearly significant decrease in subjective daytime sleepiness. CONCLUSIONS: Morning-dosed modafinil promotes nocturnal sleep, normalizes sleep architecture, and decreases daytime sleepiness in abstinent cocaine users. These effects may be relevant in the treatment of cocaine dependence.","[{'text': 'modafinil', 'type': 'Chemical', 'start': 23, 'end': 32, 'mesh': 'C048833'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 53, 'end': 60, 'mesh': 'D003042'}, {'text': 'modafinil', 'type': 'Chemical', 'start': 157, 'end': 166, 'mesh': 'C048833'}, {'text': 'daytime sleepiness', 'type': 'Disease', 'start': 180, 'end': 198, 'mesh': 'D012893'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 210, 'end': 217, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 240, 'end': 247, 'mesh': 'D003042'}, {'text': 'modafinil', 'type': 'Chemical', 'start': 305, 'end': 314, 'mesh': 'C048833'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 919, 'end': 926, 'mesh': 'D003042'}, {'text': 'modafinil', 'type': 'Chemical', 'start': 1029, 'end': 1038, 'mesh': 'C048833'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1111, 'end': 1118, 'mesh': 'D003042'}, {'text': 'modafinil', 'type': 'Chemical', 'start': 1157, 'end': 1166, 'mesh': 'C048833'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1389, 'end': 1396, 'mesh': 'D003042'}, {'text': 'modafinil', 'type': 'Chemical', 'start': 1465, 'end': 1474, 'mesh': 'C048833'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1478, 'end': 1485, 'mesh': 'D003042'}, {'text': 'Modafinil', 'type': 'Chemical', 'start': 1510, 'end': 1519, 'mesh': 'C048833'}, {'text': 'daytime sleepiness', 'type': 'Disease', 'start': 1669, 'end': 1687, 'mesh': 'D012893'}, {'text': 'modafinil', 'type': 'Chemical', 'start': 1716, 'end': 1725, 'mesh': 'C048833'}, {'text': 'daytime sleepiness', 'type': 'Disease', 'start': 1797, 'end': 1815, 'mesh': 'D012893'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1829, 'end': 1836, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1894, 'end': 1901, 'mesh': 'D003042'}]"
+264,20520283,Efficacy and safety of asenapine in a placebo- and haloperidol-controlled trial in patients with acute exacerbation of schizophrenia.,"Asenapine is approved by the Food and Drugs Administration in adults for acute treatment of schizophrenia or of manic or mixed episodes associated with bipolar I disorder with or without psychotic features. In a double-blind 6-week trial, 458 patients with acute schizophrenia were randomly assigned to fixed-dose treatment with asenapine at 5 mg twice daily (BID), asenapine at 10 mg BID, placebo, or haloperidol at 4 mg BID (to verify assay sensitivity). With last observations carried forward (LOCF), mean Positive and Negative Syndrome Scale total score reductions from baseline to endpoint were significantly greater with asenapine at 5 mg BID (-16.2) and haloperidol (-15.4) than placebo (-10.7; both P < 0.05); using mixed model for repeated measures (MMRM), changes at day 42 were significantly greater with asenapine at 5 and 10 mg BID (-21.3 and -19.4, respectively) and haloperidol (-20.0) than placebo (-14.6; all P < 0.05). On the Positive and Negative Syndrome Scale positive subscale, all treatments were superior to placebo with LOCF and MMRM; asenapine at 5 mg BID was superior to placebo on the negative subscale with MMRM and on the general psychopathology subscale with LOCF and MMRM. Treatment-related adverse events (AEs) occurred in 44% and 52%, 57%, and 41% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Extrapyramidal symptoms reported as AEs occurred in 15% and 18%, 34%, and 10% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Across all groups, no more than 5% of patients had clinically significant weight change. Post hoc analyses indicated that efficacy was similar with asenapine and haloperidol; greater contrasts were seen in AEs, especially extrapyramidal symptoms.","[{'text': 'asenapine', 'type': 'Chemical', 'start': 23, 'end': 32, 'mesh': 'C522667'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 51, 'end': 62, 'mesh': 'D006220'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 119, 'end': 132, 'mesh': 'D012559'}, {'text': 'Asenapine', 'type': 'Chemical', 'start': 134, 'end': 143, 'mesh': 'C522667'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 226, 'end': 239, 'mesh': 'D012559'}, {'text': 'manic', 'type': 'Disease', 'start': 246, 'end': 251, 'mesh': 'D001714'}, {'text': 'bipolar I disorder', 'type': 'Disease', 'start': 286, 'end': 304, 'mesh': 'D001714'}, {'text': 'psychotic', 'type': 'Disease', 'start': 321, 'end': 330, 'mesh': 'D011618'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 397, 'end': 410, 'mesh': 'D012559'}, {'text': 'asenapine', 'type': 'Chemical', 'start': 463, 'end': 472, 'mesh': 'C522667'}, {'text': 'asenapine', 'type': 'Chemical', 'start': 500, 'end': 509, 'mesh': 'C522667'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 536, 'end': 547, 'mesh': 'D006220'}, {'text': 'asenapine', 'type': 'Chemical', 'start': 761, 'end': 770, 'mesh': 'C522667'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 795, 'end': 806, 'mesh': 'D006220'}, {'text': 'asenapine', 'type': 'Chemical', 'start': 950, 'end': 959, 'mesh': 'C522667'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1015, 'end': 1026, 'mesh': 'D006220'}, {'text': 'asenapine', 'type': 'Chemical', 'start': 1194, 'end': 1203, 'mesh': 'C522667'}, {'text': 'asenapine', 'type': 'Chemical', 'start': 1423, 'end': 1432, 'mesh': 'C522667'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1453, 'end': 1464, 'mesh': 'D006220'}, {'text': 'Extrapyramidal symptoms', 'type': 'Disease', 'start': 1500, 'end': 1523, 'mesh': 'D001480'}, {'text': 'asenapine', 'type': 'Chemical', 'start': 1585, 'end': 1594, 'mesh': 'C522667'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1615, 'end': 1626, 'mesh': 'D006220'}, {'text': 'asenapine', 'type': 'Chemical', 'start': 1810, 'end': 1819, 'mesh': 'C522667'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1824, 'end': 1835, 'mesh': 'D006220'}, {'text': 'extrapyramidal symptoms', 'type': 'Disease', 'start': 1884, 'end': 1907, 'mesh': 'D001480'}]"
+265,20588063,"Permeability, ultrastructural changes, and distribution of novel proteins in the glomerular barrier in early puromycin aminonucleoside nephrosis.","BACKGROUND/AIMS: It is still unclear what happens in the glomerulus when proteinuria starts. Using puromycin aminonucleoside nephrosis (PAN) rats, we studied early ultrastructural and permeability changes in relation to the expression of the podocyte-associated molecules nephrin, a-actinin, dendrin, and plekhh2, the last two of which were only recently discovered in podocytes. METHODS: Using immune stainings, semiquantitative measurement was performed under the electron microscope. Permeability was assessed using isolated kidney perfusion with tracers. Possible effects of ACE inhibition were tested. RESULTS: By day 2, some patchy foot process effacement, but no proteinuria, appeared. The amount of nephrin was reduced in both diseased and normal areas. The other proteins showed few changes, which were limited to diseased areas. By day 4, foot process effacement was complete and proteinuria appeared in parallel with signs of size barrier damage. Nephrin decreased further, while dendrin and plekhh2 also decreased but a-actinin remained unchanged. ACE inhibition had no significant protective effect. CONCLUSIONS: PAN glomeruli already showed significant pathology by day 4, despite relatively mild proteinuria. This was preceded by altered nephrin expression, supporting its pivotal role in podocyte morphology. The novel proteins dendrin and plekhh2 were both reduced, suggesting roles in PAN, whereas a-actinin was unchanged.","[{'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 109, 'end': 134, 'mesh': 'D011692'}, {'text': 'nephrosis', 'type': 'Disease', 'start': 135, 'end': 144, 'mesh': 'D009401'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 219, 'end': 230, 'mesh': 'D011507'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 245, 'end': 270, 'mesh': 'D011692'}, {'text': 'nephrosis', 'type': 'Disease', 'start': 271, 'end': 280, 'mesh': 'D009401'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 816, 'end': 827, 'mesh': 'D011507'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1036, 'end': 1047, 'mesh': 'D011507'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1357, 'end': 1368, 'mesh': 'D011507'}]"
+266,19820426,Twin preterm neonates with cardiac toxicity related to lopinavir/ritonavir therapy.,"We report twin neonates who were born prematurely at 32 weeks of gestation to a mother with human immunodeficiency virus infection. One of the twins developed complete heart block and dilated cardiomyopathy related to lopinavir/ritonavir therapy, a boosted protease-inhibitor agent, while the other twin developed mild bradycardia. We recommend caution in the use of lopinavir/ritonavir in the immediate neonatal period.","[{'text': 'cardiac toxicity', 'type': 'Disease', 'start': 27, 'end': 43, 'mesh': 'D066126'}, {'text': 'lopinavir/ritonavir', 'type': 'Chemical', 'start': 55, 'end': 74, 'mesh': 'C558899'}, {'text': 'human immunodeficiency virus infection', 'type': 'Disease', 'start': 176, 'end': 214, 'mesh': 'D015658'}, {'text': 'heart block', 'type': 'Disease', 'start': 252, 'end': 263, 'mesh': 'D006327'}, {'text': 'dilated cardiomyopathy', 'type': 'Disease', 'start': 268, 'end': 290, 'mesh': 'D002311'}, {'text': 'lopinavir/ritonavir', 'type': 'Chemical', 'start': 302, 'end': 321, 'mesh': 'C558899'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 403, 'end': 414, 'mesh': 'D001919'}, {'text': 'lopinavir/ritonavir', 'type': 'Chemical', 'start': 451, 'end': 470, 'mesh': 'C558899'}]"
+267,1616457,Learning of rats under amnesia caused by pentobarbital.,"Dissociated learning of rats in the normal state and the state of amnesia produced by pentobarbital (15 mg/kg, ip) was carried out. Rats were trained to approach a shelf where they received food reinforcement. In Group 1 the rats were trained under the influence of pentobarbital to run to the same shelf as in the normal state. In Group 2 the rats were trained to approach different shelves in different drug states. It was shown that memory dissociation occurred in both groups. Differences in the parameters of training under the influence of pentobarbital between Groups 1 and 2 were revealed. These findings show that the brain-dissociated state induced by pentobarbital is formed with the participation of the mechanisms of information perception.","[{'text': 'amnesia', 'type': 'Disease', 'start': 23, 'end': 30, 'mesh': 'D000647'}, {'text': 'pentobarbital', 'type': 'Chemical', 'start': 41, 'end': 54, 'mesh': 'D010424'}, {'text': 'amnesia', 'type': 'Disease', 'start': 122, 'end': 129, 'mesh': 'D000647'}, {'text': 'pentobarbital', 'type': 'Chemical', 'start': 142, 'end': 155, 'mesh': 'D010424'}, {'text': 'pentobarbital', 'type': 'Chemical', 'start': 322, 'end': 335, 'mesh': 'D010424'}, {'text': 'memory dissociation', 'type': 'Disease', 'start': 492, 'end': 511, 'mesh': 'D008569'}, {'text': 'pentobarbital', 'type': 'Chemical', 'start': 602, 'end': 615, 'mesh': 'D010424'}, {'text': 'pentobarbital', 'type': 'Chemical', 'start': 718, 'end': 731, 'mesh': 'D010424'}]"
+268,567256,Angiosarcoma of the liver associated with diethylstilbestrol.,Angiosarcoma of the liver occurred in a 76-year-old man who had been treated for a well-differentiated adenocarcinoma of the liver with diethylstilbestrol for 13 years. Angiosarcoma was also present within pulmonary and renal arteries. The possibility that the intraarterial lesions might represent independent primary tumors is considered.,"[{'text': 'diethylstilbestrol', 'type': 'Chemical', 'start': 42, 'end': 60, 'mesh': 'D004054'}, {'text': 'diethylstilbestrol', 'type': 'Chemical', 'start': 198, 'end': 216, 'mesh': 'D004054'}, {'text': 'Angiosarcoma', 'type': 'Disease', 'start': 231, 'end': 243, 'mesh': 'D006394'}, {'text': 'intraarterial lesions', 'type': 'Disease', 'start': 323, 'end': 344, 'mesh': 'D014652'}, {'text': 'tumors', 'type': 'Disease', 'start': 381, 'end': 387, 'mesh': 'D009369'}]"
+269,17439425,Role of xanthine oxidase in dexamethasone-induced hypertension in rats.,"1. Glucocorticoid-induced hypertension (GC-HT) in the rat is associated with nitric oxide-redox imbalance. 2. We studied the role of xanthine oxidase (XO), which is implicated in the production of reactive oxygen species, in dexamethasone-induced hypertension (dex-HT). 3. Thirty male Sprague-Dawley rats were divided randomly into four treatment groups: saline, dexamethasone (dex), allopurinol plus saline, and allopurinol plus dex. 4. Systolic blood pressures (SBP) and bodyweights were recorded each alternate day. Thymus weight was used as a marker of glucocorticoid activity, and serum urate to assess XO inhibition. 5. Dex increased SBP (110 +/- 2-126 +/- 3 mmHg; P < 0.001) and decreased thymus (P < 0.001) and bodyweights (P"" < 0.01). Allopurinol decreased serum urate from 76 +/- 5 to 30 +/- 3 micromol/L (P < 0.001) in saline and from 84 +/- 13 to 28 +/- 2 micromol/L in dex-treated (P < 0.01) groups. 6. Allopurinol did not prevent dex-HT. This, together with our previous findings that allopurinol failed to prevent adrenocorticotrophic hormone induced hypertension, suggests that XO activity is not a major determinant of GC-HT in the rat.","[{'text': 'xanthine', 'type': 'Chemical', 'start': 8, 'end': 16, 'mesh': 'D019820'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 28, 'end': 41, 'mesh': 'D003907'}, {'text': 'hypertension', 'type': 'Disease', 'start': 50, 'end': 62, 'mesh': 'D006973'}, {'text': 'hypertension', 'type': 'Disease', 'start': 98, 'end': 110, 'mesh': 'D006973'}, {'text': 'HT', 'type': 'Disease', 'start': 115, 'end': 117, 'mesh': 'D006973'}, {'text': 'nitric oxide', 'type': 'Chemical', 'start': 149, 'end': 161, 'mesh': 'D009569'}, {'text': 'xanthine', 'type': 'Chemical', 'start': 205, 'end': 213, 'mesh': 'D019820'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 297, 'end': 310, 'mesh': 'D003907'}, {'text': 'hypertension', 'type': 'Disease', 'start': 319, 'end': 331, 'mesh': 'D006973'}, {'text': 'dex', 'type': 'Chemical', 'start': 333, 'end': 336, 'mesh': 'D003907'}, {'text': 'HT', 'type': 'Disease', 'start': 337, 'end': 339, 'mesh': 'D006973'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 435, 'end': 448, 'mesh': 'D003907'}, {'text': 'dex', 'type': 'Chemical', 'start': 450, 'end': 453, 'mesh': 'D003907'}, {'text': 'allopurinol', 'type': 'Chemical', 'start': 456, 'end': 467, 'mesh': 'D000493'}, {'text': 'allopurinol', 'type': 'Chemical', 'start': 485, 'end': 496, 'mesh': 'D000493'}, {'text': 'dex', 'type': 'Chemical', 'start': 502, 'end': 505, 'mesh': 'D003907'}, {'text': 'urate', 'type': 'Chemical', 'start': 664, 'end': 669, 'mesh': 'D014527'}, {'text': 'Dex', 'type': 'Chemical', 'start': 698, 'end': 701, 'mesh': 'D003907'}, {'text': 'increased SBP', 'type': 'Disease', 'start': 702, 'end': 715, 'mesh': 'D006973'}, {'text': 'decreased thymus (P < 0.001) and bodyweights', 'type': 'Disease', 'start': 758, 'end': 802, 'mesh': 'D015431'}, {'text': 'Allopurinol', 'type': 'Chemical', 'start': 816, 'end': 827, 'mesh': 'D000493'}, {'text': 'urate', 'type': 'Chemical', 'start': 844, 'end': 849, 'mesh': 'D014527'}, {'text': 'dex', 'type': 'Chemical', 'start': 954, 'end': 957, 'mesh': 'D003907'}, {'text': 'Allopurinol', 'type': 'Chemical', 'start': 988, 'end': 999, 'mesh': 'D000493'}, {'text': 'dex', 'type': 'Chemical', 'start': 1016, 'end': 1019, 'mesh': 'D003907'}, {'text': 'HT', 'type': 'Disease', 'start': 1020, 'end': 1022, 'mesh': 'D006973'}, {'text': 'allopurinol', 'type': 'Chemical', 'start': 1071, 'end': 1082, 'mesh': 'D000493'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1138, 'end': 1150, 'mesh': 'D006973'}, {'text': 'HT', 'type': 'Disease', 'start': 1211, 'end': 1213, 'mesh': 'D006973'}]"
+270,9351491,Extrapyramidal side effects with risperidone and haloperidol at comparable D2 receptor occupancy levels.,"Risperidone is an antipsychotic drug with high affinity at dopamine D2 and serotonin 5-HT2 receptors. Previous clinical studies have proposed that risperidone's pharmacologic profile may produce improved efficacy for negative psychotic symptoms and decreased propensity for extrapyramidal side effects; features shared by so-called 'atypical' neuroleptics. To determine if routine risperidone treatment is associated with a unique degree of D2 receptor occupancy and pattern of clinical effects, we used [123I]IBZM SPECT to determine D2 occupancy in subjects treated with routine clinical doses of risperidone (n = 12) or haloperidol (n = 7). Both risperidone and haloperidol produced D2 occupancy levels between approximately 60 and 90% at standard clinical doses. There was no significant difference between occupancy levels obtained with haloperidol or risperidone. Drug-induced parkinsonism was observed in subjects treated with risperidone (42%) and haloperidol (29%) and was observed at occupancy levels above 60%. Based on these observations, it is concluded that 5-HT2 blockade obtained with risperidone at D2 occupancy rates of 60% and above does not appear to protect against the risk for extrapyramidal side effects.","[{'text': 'risperidone', 'type': 'Chemical', 'start': 33, 'end': 44, 'mesh': 'D018967'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 49, 'end': 60, 'mesh': 'D006220'}, {'text': 'Risperidone', 'type': 'Chemical', 'start': 105, 'end': 116, 'mesh': 'D018967'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 164, 'end': 172, 'mesh': 'D004298'}, {'text': 'serotonin 5-HT2', 'type': 'Chemical', 'start': 180, 'end': 195, 'mesh': 'D044348'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 252, 'end': 263, 'mesh': 'D018967'}, {'text': 'psychotic symptoms', 'type': 'Disease', 'start': 331, 'end': 349, 'mesh': 'D011618'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 486, 'end': 497, 'mesh': 'D018967'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 703, 'end': 714, 'mesh': 'D018967'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 727, 'end': 738, 'mesh': 'D006220'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 753, 'end': 764, 'mesh': 'D018967'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 769, 'end': 780, 'mesh': 'D006220'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 946, 'end': 957, 'mesh': 'D006220'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 961, 'end': 972, 'mesh': 'D018967'}, {'text': 'Drug-induced parkinsonism', 'type': 'Disease', 'start': 974, 'end': 999, 'mesh': 'D010302'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 1038, 'end': 1049, 'mesh': 'D018967'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1060, 'end': 1071, 'mesh': 'D006220'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 1205, 'end': 1216, 'mesh': 'D018967'}]"
+271,18752389,Simvastatin-ezetimibe-induced hepatic failure necessitating liver transplantation.,"Abstract Serum aminotransferase elevations are a commonly known adverse effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy. However, hepatotoxic events have not been widely published with ezetimibe or the combination agent simvastatin-ezetimibe. We describe a 70-year-old Hispanic woman who developed fulminant hepatic failure necessitating liver transplantation 10 weeks after conversion from simvastatin 40 mg/day to simvastatin 10 mg-ezetimibe 40 mg/day. The patient's lipid panel had been maintained with simvastatin for 18 months before the conversion without evidence of hepatotoxicity. A routine laboratory work-up 10 weeks after conversion revealed elevated serum aminotransferase levels. Simvastatinezetimibe and escitalopram (which she was taking for depression) were discontinued, and other potential causes of hepatotoxicity were excluded. A repeat work-up revealed further elevations in aminotransferase levels, and liver biopsy revealed evidence of moderate-to-severe drug toxicity. She underwent liver transplantation with an uneventful postoperative course. Her aminotransferase levels returned to normal by postoperative day 23, and her 2-year follow-up showed no adverse events. Ezetimibe undergoes extensive glucuronidation by uridine diphosphate glucoronosyltransferases (UGT) in the intestine and liver and may have inhibited the glucuronidation of simvastatin hydroxy acid, resulting in increased simvastatin exposure and subsequent hepatotoxicity. To our knowledge, this is the first case report of simvastatin-ezetimibe-induced liver failure that resulted in liver transplantation. We postulate that the mechanism of the simvastatinezetimibe-induced hepatotoxicity is the increased simvastatin exposure by ezetimibe inhibition of UGT enzymes. Clinicians should be aware of potential hepatotoxicity with simvastatin-ezetimibe especially in elderly patients and should carefully monitor serum aminotransferase levels when starting therapy and titrating the dosage.","[{'text': 'Simvastatin-ezetimibe', 'type': 'Chemical', 'start': 0, 'end': 21, 'mesh': 'C492458'}, {'text': 'hepatic failure', 'type': 'Disease', 'start': 30, 'end': 45, 'mesh': 'D017093'}, {'text': 'statin', 'type': 'Chemical', 'start': 224, 'end': 230, 'mesh': 'D019821'}, {'text': 'hepatotoxic', 'type': 'Disease', 'start': 250, 'end': 261, 'mesh': 'D056486'}, {'text': 'ezetimibe', 'type': 'Chemical', 'start': 305, 'end': 314, 'mesh': 'C108606'}, {'text': 'simvastatin-ezetimibe', 'type': 'Chemical', 'start': 340, 'end': 361, 'mesh': 'C492458'}, {'text': 'fulminant hepatic failure', 'type': 'Disease', 'start': 418, 'end': 443, 'mesh': 'D017114'}, {'text': 'simvastatin', 'type': 'Chemical', 'start': 511, 'end': 522, 'mesh': 'D019821'}, {'text': 'simvastatin 10 mg-ezetimibe 40 mg', 'type': 'Chemical', 'start': 536, 'end': 569, 'mesh': 'C492458'}, {'text': 'simvastatin', 'type': 'Chemical', 'start': 626, 'end': 637, 'mesh': 'D019821'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 694, 'end': 708, 'mesh': 'D056486'}, {'text': 'Simvastatinezetimibe', 'type': 'Chemical', 'start': 814, 'end': 834, 'mesh': 'C492458'}, {'text': 'escitalopram', 'type': 'Chemical', 'start': 839, 'end': 851, 'mesh': 'D015283'}, {'text': 'depression', 'type': 'Disease', 'start': 878, 'end': 888, 'mesh': 'D003866'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 939, 'end': 953, 'mesh': 'D056486'}, {'text': 'drug toxicity', 'type': 'Disease', 'start': 1099, 'end': 1112, 'mesh': 'D064420'}, {'text': 'Ezetimibe', 'type': 'Chemical', 'start': 1314, 'end': 1323, 'mesh': 'C108606'}, {'text': 'uridine diphosphate', 'type': 'Chemical', 'start': 1363, 'end': 1382, 'mesh': 'D014530'}, {'text': 'simvastatin hydroxy acid', 'type': 'Chemical', 'start': 1487, 'end': 1511, 'mesh': 'C532833'}, {'text': 'simvastatin', 'type': 'Chemical', 'start': 1536, 'end': 1547, 'mesh': 'D019821'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 1572, 'end': 1586, 'mesh': 'D056486'}, {'text': 'simvastatin-ezetimibe', 'type': 'Chemical', 'start': 1639, 'end': 1660, 'mesh': 'C492458'}, {'text': 'liver failure', 'type': 'Disease', 'start': 1669, 'end': 1682, 'mesh': 'D017093'}, {'text': 'simvastatinezetimibe', 'type': 'Chemical', 'start': 1762, 'end': 1782, 'mesh': 'C492458'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 1791, 'end': 1805, 'mesh': 'D056486'}, {'text': 'simvastatin', 'type': 'Chemical', 'start': 1823, 'end': 1834, 'mesh': 'D019821'}, {'text': 'ezetimibe', 'type': 'Chemical', 'start': 1847, 'end': 1856, 'mesh': 'C108606'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 1924, 'end': 1938, 'mesh': 'D056486'}, {'text': 'simvastatin-ezetimibe', 'type': 'Chemical', 'start': 1944, 'end': 1965, 'mesh': 'C492458'}]"
+272,20098969,"Oral manifestations of ""meth mouth"": a case report.","AIM: The aim of the documentation of this clinical case is to make clinicians aware of ""meth mouth"" and the medical risks associated with this serious condition. BACKGROUND: Methamphetamine is a very addictive, powerful stimulant that increases wakefulness and physical activity and can produce other effects such as cardiac dysrhythmias, hypertension, hallucinations, and violent behavior. Dental patients abusing methamphetamine can present with poor oral hygiene, xerostomia, rampant caries (""meth mouth""), and excessive tooth wear. Oral rehabilitation of patients using methamphetamine can be challenging. CASE DESCRIPTION: A 30-year-old Caucasian woman presented with dental pain, bad breath, and self-reported poor esthetics. A comprehensive examination including her medical history, panoramic radiograph, and intraoral examination revealed 19 carious lesions, which is not very common for a healthy adult. She reported her use of methamphetamine for five years and had not experienced any major carious episodes before she started using the drug. SUMMARY: The patient's medical and dental histories along with radiographic and clinical findings lead to a diagnosis of ""meth mouth."" Although three different dental treatment modalities (either conventional or implant-supported) have been offered to the patient since August 2007, the patient has yet to initiate any treatment. CLINICAL SIGNIFICANCE: This clinical case showing oral manifestations of meth mouth was presented to help dental practitioners recognize and manage patients who may be abusing methamphetamines. Dental practitioners also may be skeptical about the reliability of appointment keeping by these patients, as they frequently miss their appointments without reasonable justification.","[{'text': 'meth mouth', 'type': 'Disease', 'start': 24, 'end': 34, 'mesh': '-1'}, {'text': 'meth mouth', 'type': 'Disease', 'start': 140, 'end': 150, 'mesh': '-1'}, {'text': 'Methamphetamine', 'type': 'Chemical', 'start': 226, 'end': 241, 'mesh': 'D008694'}, {'text': 'cardiac dysrhythmias', 'type': 'Disease', 'start': 369, 'end': 389, 'mesh': 'D001145'}, {'text': 'hypertension', 'type': 'Disease', 'start': 391, 'end': 403, 'mesh': 'D006973'}, {'text': 'hallucinations', 'type': 'Disease', 'start': 405, 'end': 419, 'mesh': 'D006212'}, {'text': 'violent behavior', 'type': 'Disease', 'start': 425, 'end': 441, 'mesh': 'D001523'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 467, 'end': 482, 'mesh': 'D008694'}, {'text': 'xerostomia', 'type': 'Disease', 'start': 519, 'end': 529, 'mesh': 'D014987'}, {'text': 'caries', 'type': 'Disease', 'start': 539, 'end': 545, 'mesh': 'D003731'}, {'text': 'meth mouth', 'type': 'Disease', 'start': 548, 'end': 558, 'mesh': '-1'}, {'text': 'tooth wear', 'type': 'Disease', 'start': 576, 'end': 586, 'mesh': 'D057085'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 626, 'end': 641, 'mesh': 'D008694'}, {'text': 'pain', 'type': 'Disease', 'start': 732, 'end': 736, 'mesh': 'D010146'}, {'text': 'bad breath', 'type': 'Disease', 'start': 738, 'end': 748, 'mesh': 'D012120'}, {'text': 'carious lesions', 'type': 'Disease', 'start': 903, 'end': 918, 'mesh': 'D003731'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 990, 'end': 1005, 'mesh': 'D008694'}, {'text': 'carious episodes', 'type': 'Disease', 'start': 1055, 'end': 1071, 'mesh': 'D003731'}, {'text': 'meth mouth', 'type': 'Disease', 'start': 1229, 'end': 1239, 'mesh': '-1'}, {'text': 'meth mouth', 'type': 'Disease', 'start': 1510, 'end': 1520, 'mesh': '-1'}, {'text': 'methamphetamines', 'type': 'Chemical', 'start': 1613, 'end': 1629, 'mesh': 'D008694'}]"
+273,9653867,Thyroxine abuse: an unusual case of thyrotoxicosis in pregnancy.,"Eating disorders and the associated behavioural problems and drug abuse are uncommon in pregnancy. When they do occur they are often unrecognized because of denial but when significant may pose a risk to both the mother and her fetus. This case illustrates a number of problems that may be encountered in women with eating disorders in pregnancy, including prolonged and recurrent metabolic disturbances and diuretic abuse. In particular it illustrates the derangements of thyroid function seen in pregnant women with eating disorders and reminds us that when a cause for thyrotoxicosis remains obscure, thyroxine abuse should be considered and explored.","[{'text': 'Thyroxine', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D013974'}, {'text': 'thyrotoxicosis', 'type': 'Disease', 'start': 36, 'end': 50, 'mesh': 'D013971'}, {'text': 'Eating disorders', 'type': 'Disease', 'start': 65, 'end': 81, 'mesh': 'D001068'}, {'text': 'drug abuse', 'type': 'Disease', 'start': 126, 'end': 136, 'mesh': 'D019966'}, {'text': 'eating disorders', 'type': 'Disease', 'start': 381, 'end': 397, 'mesh': 'D001068'}, {'text': 'eating disorders', 'type': 'Disease', 'start': 583, 'end': 599, 'mesh': 'D001068'}, {'text': 'thyrotoxicosis', 'type': 'Disease', 'start': 637, 'end': 651, 'mesh': 'D013971'}, {'text': 'thyroxine', 'type': 'Chemical', 'start': 669, 'end': 678, 'mesh': 'D013974'}]"
+274,17608141,Attenuation of methamphetamine-induced nigrostriatal dopaminergic neurotoxicity in mice by lipopolysaccharide pretreatment.,"Immunological activation has been proposed to play a role in methamphetamine-induced dopaminergic terminal damage. In this study, we examined the roles of lipopolysaccharide, a pro-inflammatory and inflammatory factor, treatment in modulating the methamphetamine-induced nigrostriatal dopamine neurotoxicity. Lipopolysaccharide pretreatment did not affect the basal body temperature or methamphetamine-elicited hyperthermia three days later. Such systemic lipopolysaccharide treatment mitigated methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions in a dose-dependent manner. As the most potent dose (1 mg/kg) of lipopolysaccharide was administered two weeks, one day before or after the methamphetamine dosing regimen, methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions remained unaltered. Moreover, systemic lipopolysaccharide pretreatment (1 mg/kg) attenuated local methamphetamine infusion-produced dopamine and 3,4-dihydroxyphenylacetic acid depletions in the striatum, indicating that the protective effect of lipopolysaccharide is less likely due to interrupted peripheral distribution or metabolism of methamphetamine. We concluded a critical time window for systemic lipopolysaccharide pretreatment in exerting effective protection against methamphetamine-induced nigrostriatal dopamine neurotoxicity.","[{'text': 'methamphetamine', 'type': 'Chemical', 'start': 15, 'end': 30, 'mesh': 'D008694'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 66, 'end': 79, 'mesh': 'D020258'}, {'text': 'lipopolysaccharide', 'type': 'Chemical', 'start': 91, 'end': 109, 'mesh': 'D008070'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 185, 'end': 200, 'mesh': 'D008694'}, {'text': 'dopaminergic terminal damage', 'type': 'Disease', 'start': 209, 'end': 237, 'mesh': 'D009422'}, {'text': 'lipopolysaccharide', 'type': 'Chemical', 'start': 279, 'end': 297, 'mesh': 'D008070'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 371, 'end': 386, 'mesh': 'D008694'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 409, 'end': 417, 'mesh': 'D004298'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 418, 'end': 431, 'mesh': 'D020258'}, {'text': 'Lipopolysaccharide', 'type': 'Chemical', 'start': 433, 'end': 451, 'mesh': 'D008070'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 510, 'end': 525, 'mesh': 'D008694'}, {'text': 'hyperthermia', 'type': 'Disease', 'start': 535, 'end': 547, 'mesh': 'D005334'}, {'text': 'lipopolysaccharide', 'type': 'Chemical', 'start': 580, 'end': 598, 'mesh': 'D008070'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 619, 'end': 634, 'mesh': 'D008694'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 652, 'end': 660, 'mesh': 'D004298'}, {'text': '3,4-dihydroxyphenylacetic acid', 'type': 'Chemical', 'start': 665, 'end': 695, 'mesh': 'D015102'}, {'text': 'lipopolysaccharide', 'type': 'Chemical', 'start': 772, 'end': 790, 'mesh': 'D008070'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 847, 'end': 862, 'mesh': 'D008694'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 879, 'end': 894, 'mesh': 'D008694'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 912, 'end': 920, 'mesh': 'D004298'}, {'text': '3,4-dihydroxyphenylacetic acid', 'type': 'Chemical', 'start': 925, 'end': 955, 'mesh': 'D015102'}, {'text': 'lipopolysaccharide', 'type': 'Chemical', 'start': 1006, 'end': 1024, 'mesh': 'D008070'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 1065, 'end': 1080, 'mesh': 'D008694'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1099, 'end': 1107, 'mesh': 'D004298'}, {'text': '3,4-dihydroxyphenylacetic acid', 'type': 'Chemical', 'start': 1112, 'end': 1142, 'mesh': 'D015102'}, {'text': 'lipopolysaccharide', 'type': 'Chemical', 'start': 1212, 'end': 1230, 'mesh': 'D008070'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 1306, 'end': 1321, 'mesh': 'D008694'}, {'text': 'lipopolysaccharide', 'type': 'Chemical', 'start': 1372, 'end': 1390, 'mesh': 'D008070'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 1445, 'end': 1460, 'mesh': 'D008694'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1483, 'end': 1491, 'mesh': 'D004298'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 1492, 'end': 1505, 'mesh': 'D020258'}]"
+275,2559236,Effect of converting enzyme inhibition on the course of adriamycin-induced nephropathy.,"The effect of the converting enzyme inhibitor (CEI) enalapril was assessed in Munich-Wistar rats with established adriamycin nephrosis. Rats were given a single dose of adriamycin and one month later divided into four groups matched for albuminuria, blood pressure, and plasma albumin concentration. Groups 1 and 3 remained untreated while groups 2 and 4 received enalapril. Groups 1 and 2 underwent micropuncture studies after 10 days. These short-term studies showed that enalapril reduced arterial blood pressure (101 +/- 2 vs. 124 +/- 3 mm Hg, group 2 vs. 1, P less than 0.05) and glomerular capillary pressure (54 +/- 1 vs. 61 +/- 2 mm Hg, P less than 0.05) without reducing albuminuria (617 +/- 50 vs. 570 +/- 47 mg/day) or GFR (1.03 +/- 0.04 vs. 1.04 +/- 0.11 ml/min). Groups 3 and 4 were studied at four and at six months to assess the effect of enalapril on progression of renal injury in adriamycin nephrosis. Chronic enalapril treatment reduced blood pressure without reducing albuminuria in group 4. Untreated group 3 rats exhibited a progressive reduction in GFR (0.35 +/- 0.08 ml/min at 4 months, 0.27 +/- 0.07 ml/min at 6 months). Enalapril treatment blunted but did not prevent reduction in GFR in group 4 (0.86 +/- 0.15 ml/min at 4 months, 0.69 +/- 0.13 ml/min at 6 months, both P less than 0.05 vs. group 3). Reduction in GFR was associated with the development of glomerular sclerosis in both treated and untreated rats.(ABSTRACT TRUNCATED AT 250 WORDS)","[{'text': 'adriamycin', 'type': 'Chemical', 'start': 56, 'end': 66, 'mesh': 'D004317'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 75, 'end': 86, 'mesh': 'D007674'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 140, 'end': 149, 'mesh': 'D004656'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 202, 'end': 212, 'mesh': 'D004317'}, {'text': 'nephrosis', 'type': 'Disease', 'start': 213, 'end': 222, 'mesh': 'D009401'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 257, 'end': 267, 'mesh': 'D004317'}, {'text': 'albuminuria', 'type': 'Disease', 'start': 325, 'end': 336, 'mesh': 'D000419'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 452, 'end': 461, 'mesh': 'D004656'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 562, 'end': 571, 'mesh': 'D004656'}, {'text': 'albuminuria', 'type': 'Disease', 'start': 768, 'end': 779, 'mesh': 'D000419'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 942, 'end': 951, 'mesh': 'D004656'}, {'text': 'renal injury', 'type': 'Disease', 'start': 970, 'end': 982, 'mesh': 'D007674'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 986, 'end': 996, 'mesh': 'D004317'}, {'text': 'nephrosis', 'type': 'Disease', 'start': 997, 'end': 1006, 'mesh': 'D009401'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 1016, 'end': 1025, 'mesh': 'D004656'}, {'text': 'albuminuria', 'type': 'Disease', 'start': 1076, 'end': 1087, 'mesh': 'D000419'}, {'text': 'Enalapril', 'type': 'Chemical', 'start': 1234, 'end': 1243, 'mesh': 'D004656'}, {'text': 'glomerular sclerosis', 'type': 'Disease', 'start': 1471, 'end': 1491, 'mesh': 'D007674'}]"
+276,21029050,Butyrylcholinesterase gene mutations in patients with prolonged apnea after succinylcholine for electroconvulsive therapy.,"BACKGROUND: patients undergoing electroconvulsive therapy (ECT) often receive succinylcholine as part of the anesthetic procedure. The duration of action may be prolonged in patients with genetic variants of the butyrylcholinesterase enzyme (BChE), the most common being the K- and the A-variants. The aim of the study was to assess the clinical significance of genetic variants in butyrylcholinesterase gene (BCHE) in patients with a suspected prolonged duration of action of succinylcholine after ECT. METHODS: a total of 13 patients were referred to the Danish Cholinesterase Research Unit after ECT during 38 months. We determined the BChE activity and the BCHE genotype using molecular genetic methods, the duration of apnea, time to sufficient spontaneous ventilation and whether neuromuscular monitoring was used. The duration of apnea was compared with published data on normal subjects. RESULTS: in 11 patients, mutations were found in the BCHE gene, the K-variant being the most frequent. The duration of apnea was 5-15 min compared with 3-5.3 min from the literature. Severe distress was noted in the recovery phase in two patients. Neuromuscular monitoring was used in two patients. CONCLUSION: eleven of 13 patients with a prolonged duration of action of succinylcholine had mutations in BCHE, indicating that this is the possible reason for a prolonged period of apnea. We recommend objective neuromuscular monitoring during the first ECT.","[{'text': 'apnea', 'type': 'Disease', 'start': 64, 'end': 69, 'mesh': 'D001049'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 76, 'end': 91, 'mesh': 'D013390'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 201, 'end': 216, 'mesh': 'D013390'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 600, 'end': 615, 'mesh': 'D013390'}, {'text': 'apnea', 'type': 'Disease', 'start': 847, 'end': 852, 'mesh': 'D001049'}, {'text': 'apnea', 'type': 'Disease', 'start': 960, 'end': 965, 'mesh': 'D001049'}, {'text': 'apnea', 'type': 'Disease', 'start': 1138, 'end': 1143, 'mesh': 'D001049'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 1391, 'end': 1406, 'mesh': 'D013390'}, {'text': 'apnea', 'type': 'Disease', 'start': 1500, 'end': 1505, 'mesh': 'D001049'}]"
+277,10901305,Ketamine sedation for the reduction of children's fractures in the emergency department.,"BACKGROUND: There recently has been a resurgence in the utilization of ketamine, a unique anesthetic, for emergency-department procedures requiring sedation. The purpose of the present study was to examine the safety and efficacy of ketamine for sedation in the treatment of children's fractures in the emergency department. METHODS: One hundred and fourteen children (average age, 5.3 years; range, twelve months to ten years and ten months) who underwent closed reduction of an isolated fracture or dislocation in the emergency department at a level-I trauma center were prospectively evaluated. Ketamine hydrochloride was administered intravenously (at a dose of two milligrams per kilogram of body weight) in ninety-nine of the patients and intramuscularly (at a dose of four milligrams per kilogram of body weight) in the other fifteen. A board-certified emergency physician skilled in airway management supervised administration of the anesthetic, and the patients were monitored by a registered nurse. Any pain during the reduction was rated by the orthopaedic surgeon treating the patient according to the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). RESULTS: The average time from intravenous administration of ketamine to manipulation of the fracture or dislocation was one minute and thirty-six seconds (range, twenty seconds to five minutes), and the average time from intramuscular administration to manipulation was four minutes and forty-two seconds (range, sixty seconds to fifteen minutes). The average score according to the Children's Hospital of Eastern Ontario Pain Scale was 6.4 points (range, 5 to 10 points), reflecting minimal or no pain during fracture reduction. Adequate fracture reduction was obtained in 111 of the children. Ninety-nine percent (sixty-eight) of the sixty-nine parents present during the reduction were pleased with the sedation and would allow it to be used again in a similar situation. Patency of the airway and independent respiration were maintained in all of the patients. Blood pressure and heart rate remained stable. Minor side effects included nausea (thirteen patients), emesis (eight of the thirteen patients with nausea), clumsiness (evident as ataxic movements in ten patients), and dysphoric reaction (one patient). No long-term sequelae were noted, and no patients had hallucinations or nightmares. CONCLUSIONS: Ketamine reliably, safely, and quickly provided adequate sedation to effectively facilitate the reduction of children's fractures in the emergency department at our institution. Ketamine should only be used in an environment such as the emergency department, where proper one-on-one monitoring is used and board-certified physicians skilled in airway management are directly involved in the care of the patient.","[{'text': 'Ketamine', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D007649'}, {'text': 'fractures', 'type': 'Disease', 'start': 50, 'end': 59, 'mesh': 'D050723'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 160, 'end': 168, 'mesh': 'D007649'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 322, 'end': 330, 'mesh': 'D007649'}, {'text': 'fractures', 'type': 'Disease', 'start': 375, 'end': 384, 'mesh': 'D050723'}, {'text': 'fracture', 'type': 'Disease', 'start': 578, 'end': 586, 'mesh': 'D050723'}, {'text': 'dislocation', 'type': 'Disease', 'start': 590, 'end': 601, 'mesh': 'D004204'}, {'text': 'trauma', 'type': 'Disease', 'start': 643, 'end': 649, 'mesh': 'D014947'}, {'text': 'Ketamine hydrochloride', 'type': 'Chemical', 'start': 687, 'end': 709, 'mesh': 'D007649'}, {'text': 'pain', 'type': 'Disease', 'start': 1102, 'end': 1106, 'mesh': 'D010146'}, {'text': 'Pain', 'type': 'Disease', 'start': 1242, 'end': 1246, 'mesh': 'D010146'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 1324, 'end': 1332, 'mesh': 'D007649'}, {'text': 'fracture', 'type': 'Disease', 'start': 1356, 'end': 1364, 'mesh': 'D050723'}, {'text': 'dislocation', 'type': 'Disease', 'start': 1368, 'end': 1379, 'mesh': 'D004204'}, {'text': 'Pain', 'type': 'Disease', 'start': 1686, 'end': 1690, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 1762, 'end': 1766, 'mesh': 'D010146'}, {'text': 'fracture', 'type': 'Disease', 'start': 1774, 'end': 1782, 'mesh': 'D050723'}, {'text': 'fracture', 'type': 'Disease', 'start': 1803, 'end': 1811, 'mesh': 'D050723'}, {'text': 'nausea', 'type': 'Disease', 'start': 2204, 'end': 2210, 'mesh': 'D009325'}, {'text': 'emesis', 'type': 'Disease', 'start': 2232, 'end': 2238, 'mesh': 'D014839'}, {'text': 'nausea', 'type': 'Disease', 'start': 2276, 'end': 2282, 'mesh': 'D009325'}, {'text': 'clumsiness', 'type': 'Disease', 'start': 2285, 'end': 2295, 'mesh': 'D001259'}, {'text': 'ataxic movements', 'type': 'Disease', 'start': 2308, 'end': 2324, 'mesh': 'D001259'}, {'text': 'dysphoric reaction', 'type': 'Disease', 'start': 2347, 'end': 2365, 'mesh': '-1'}, {'text': 'hallucinations', 'type': 'Disease', 'start': 2435, 'end': 2449, 'mesh': 'D006212'}, {'text': 'Ketamine', 'type': 'Chemical', 'start': 2478, 'end': 2486, 'mesh': 'D007649'}, {'text': 'fractures', 'type': 'Disease', 'start': 2598, 'end': 2607, 'mesh': 'D050723'}, {'text': 'Ketamine', 'type': 'Chemical', 'start': 2656, 'end': 2664, 'mesh': 'D007649'}]"
+278,19037603,Prophylactic use of lamivudine with chronic immunosuppressive therapy for rheumatologic disorders.,"The objective of this study was to report our experience concerning the effectiveness of the prophylactic administration of lamivudine in hepatitis B virus surface antigen (HBs Ag) positive patients with rheumatologic disease. From June 2004 to October 2006, 11 HBs Ag positive patients with rheumatologic diseases, who were on both immunosuppressive and prophylactic lamivudine therapies, were retrospectively assessed. Liver function tests, hepatitis B virus (HBV) serologic markers, and HBV DNA levels of the patients during follow-up were obtained from hospital file records. Eleven patients (six male) with median age 47 years (range 27-73), median disease duration 50 months (range 9-178) and median follow-up period of patients 13.8 months (range 5-27) were enrolled in this study. Lamivudine therapy was started 3-7 days prior to immunosuppressive therapy in all patients. Baseline, liver function tests were elevated in two patients (fourth patient: ALT:122 IU/l, AST:111 IU/l, tenth patient:ALT:294 IU/l, AST:274 IU/l, with minimal changes in the liver biopsy in both). Shortly after treatment their tests normalized and during follow-up period none of the patients had abnormal liver function tests. In four patients HBV DNA levels were higher than normal at baseline. Two of these normalized and the others increased later. In three additional patients, HBV DNA levels were increased during follow-up. None of the patients had significant clinical sings of HBV activation. Lamivudine was well tolerated and was continued in all patients. Prophylactic administration of lamivudine in patients who required immunosuppressive therapy seems to be safe, well tolerated and effective in preventing HBV reactivation.","[{'text': 'lamivudine', 'type': 'Chemical', 'start': 20, 'end': 30, 'mesh': 'D019259'}, {'text': 'rheumatologic disorders', 'type': 'Disease', 'start': 74, 'end': 97, 'mesh': 'D012216'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 223, 'end': 233, 'mesh': 'D019259'}, {'text': 'hepatitis B virus surface antigen', 'type': 'Chemical', 'start': 237, 'end': 270, 'mesh': 'D006514'}, {'text': 'HBs Ag', 'type': 'Chemical', 'start': 272, 'end': 278, 'mesh': 'D006514'}, {'text': 'rheumatologic disease', 'type': 'Disease', 'start': 303, 'end': 324, 'mesh': 'D012216'}, {'text': 'HBs Ag', 'type': 'Chemical', 'start': 361, 'end': 367, 'mesh': 'D006514'}, {'text': 'rheumatologic diseases', 'type': 'Disease', 'start': 391, 'end': 413, 'mesh': 'D012216'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 467, 'end': 477, 'mesh': 'D019259'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 542, 'end': 553, 'mesh': 'D006509'}, {'text': 'Lamivudine', 'type': 'Chemical', 'start': 888, 'end': 898, 'mesh': 'D019259'}, {'text': 'abnormal liver function', 'type': 'Disease', 'start': 1279, 'end': 1302, 'mesh': 'D056486'}, {'text': 'Lamivudine', 'type': 'Chemical', 'start': 1584, 'end': 1594, 'mesh': 'D019259'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 1680, 'end': 1690, 'mesh': 'D019259'}]"
+279,20084309,Safety of transesophageal echocardiography in adults: study in a multidisciplinary hospital.,"BACKGROUND: TEE is a semi-invasive tool broadly used and its utilization associated to sedatives drugs might to affect the procedure safety. OBJECTIVE: to analyze aspects of TEE safety associated to the use of Midazolan (MZ) and Flumazenil (FL) and the influence of the clinical variables on the event rate. METHOD: prospective study with 137 patients that underwent TEE with MZ associated to moderate sedation. We analyzed the following events: complications related with the topical anesthesia, with MZ use and with the procedure. Uni- and multivariate analyses were used to test the influence of the clinical variables: age, sex, stroke, myocardiopathy (MP), duration of the test, mitral regurgitation (MR) and the MZ dose. RESULTS: All patients (65+/-16 yrs; 58% males) finished the examination. The mean doses of MZ and FL were 4.3+/-1.9 mg and 0.28+/-0.2 mg, respectively. The duration of the examination and the mean ejection fraction (EF) were 16.4+/-6.1 minutes and 60+/-9%, respectively. Mild hypoxia (SO2<90%) was the most common event (11 patients); 3 patients (2%) presented transient hypoxia due to upper airway obstruction by probe introduction and 8 (5.8%) due to hypoxia caused by MZ use. Transient hypotension (SAP<90mmHg) occurred in 1 patient (0.7%). The multivariate analysis showed that severe MR, MP (EF<45%) and high doses of MZ (>5mg) were associated with events (p<0.001). The EF was 40%, in the group with MP and 44% in the group with severe MR and it can be a factor associated with clinical events in the last group. CONCLUSION: TEE with sedation presents a low rate of events. There were no severe events and there was no need to interrupt the examinations.","[{'text': 'Midazolan', 'type': 'Chemical', 'start': 303, 'end': 312, 'mesh': 'D008874'}, {'text': 'MZ', 'type': 'Chemical', 'start': 314, 'end': 316, 'mesh': 'D008874'}, {'text': 'Flumazenil', 'type': 'Chemical', 'start': 322, 'end': 332, 'mesh': 'D005442'}, {'text': 'FL', 'type': 'Chemical', 'start': 334, 'end': 336, 'mesh': 'D005442'}, {'text': 'MZ', 'type': 'Chemical', 'start': 469, 'end': 471, 'mesh': 'D008874'}, {'text': 'MZ', 'type': 'Chemical', 'start': 595, 'end': 597, 'mesh': 'D008874'}, {'text': 'stroke', 'type': 'Disease', 'start': 726, 'end': 732, 'mesh': 'D020521'}, {'text': 'myocardiopathy', 'type': 'Disease', 'start': 734, 'end': 748, 'mesh': 'D009202'}, {'text': 'MP', 'type': 'Disease', 'start': 750, 'end': 752, 'mesh': 'D009202'}, {'text': 'mitral regurgitation', 'type': 'Disease', 'start': 777, 'end': 797, 'mesh': 'D008944'}, {'text': 'MR', 'type': 'Disease', 'start': 799, 'end': 801, 'mesh': 'D008944'}, {'text': 'MZ', 'type': 'Chemical', 'start': 811, 'end': 813, 'mesh': 'D008874'}, {'text': 'MZ', 'type': 'Chemical', 'start': 911, 'end': 913, 'mesh': 'D008874'}, {'text': 'FL', 'type': 'Chemical', 'start': 918, 'end': 920, 'mesh': 'D005442'}, {'text': 'hypoxia', 'type': 'Disease', 'start': 1096, 'end': 1103, 'mesh': 'D000860'}, {'text': 'hypoxia', 'type': 'Disease', 'start': 1191, 'end': 1198, 'mesh': 'D000860'}, {'text': 'airway obstruction', 'type': 'Disease', 'start': 1212, 'end': 1230, 'mesh': 'D000402'}, {'text': 'hypoxia', 'type': 'Disease', 'start': 1273, 'end': 1280, 'mesh': 'D000860'}, {'text': 'MZ', 'type': 'Chemical', 'start': 1291, 'end': 1293, 'mesh': 'D008874'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1309, 'end': 1320, 'mesh': 'D007022'}, {'text': 'MR', 'type': 'Disease', 'start': 1409, 'end': 1411, 'mesh': 'D008944'}, {'text': 'MP', 'type': 'Disease', 'start': 1413, 'end': 1415, 'mesh': 'D009202'}, {'text': 'MZ', 'type': 'Chemical', 'start': 1443, 'end': 1445, 'mesh': 'D008874'}, {'text': 'MP', 'type': 'Disease', 'start': 1526, 'end': 1528, 'mesh': 'D009202'}, {'text': 'MR', 'type': 'Disease', 'start': 1562, 'end': 1564, 'mesh': 'D008944'}]"
+280,8231633,Effects of calcium channel blockers on bupivacaine-induced toxicity.,"The purpose of this study was to investigate the influence of calcium channel blockers on bupivacaine-induced acute toxicity. For each of the three tested calcium channel blockers (diltiazem, verapamil and bepridil) 6 groups of mice were treated by two different doses, i.e. 2 and 10 mg/kg/i.p., or an equal volume of saline for the control group (n = 20); 15 minutes later, all the animals were injected with a single 50 mg/kg/i.p. dose of bupivacaine. The convulsant activity, the time of latency to convulse and the mortality rate were assessed in each group. The local anesthetic-induced mortality was significantly increased by the three different calcium channel blockers. The convulsant activity of bupivacaine was not significantly modified but calcium channel blockers decreased the time of latency to obtain bupivacaine-induced convulsions; this effect was less pronounced with bepridil.","[{'text': 'calcium', 'type': 'Chemical', 'start': 11, 'end': 18, 'mesh': 'D002118'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 39, 'end': 50, 'mesh': 'D002045'}, {'text': 'toxicity', 'type': 'Disease', 'start': 59, 'end': 67, 'mesh': 'D064420'}, {'text': 'calcium', 'type': 'Chemical', 'start': 131, 'end': 138, 'mesh': 'D002118'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 159, 'end': 170, 'mesh': 'D002045'}, {'text': 'toxicity', 'type': 'Disease', 'start': 185, 'end': 193, 'mesh': 'D064420'}, {'text': 'calcium', 'type': 'Chemical', 'start': 224, 'end': 231, 'mesh': 'D002118'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 250, 'end': 259, 'mesh': 'D004110'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 261, 'end': 270, 'mesh': 'D014700'}, {'text': 'bepridil', 'type': 'Chemical', 'start': 275, 'end': 283, 'mesh': 'D015764'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 510, 'end': 521, 'mesh': 'D002045'}, {'text': 'calcium', 'type': 'Chemical', 'start': 722, 'end': 729, 'mesh': 'D002118'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 775, 'end': 786, 'mesh': 'D002045'}, {'text': 'calcium', 'type': 'Chemical', 'start': 822, 'end': 829, 'mesh': 'D002118'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 887, 'end': 898, 'mesh': 'D002045'}, {'text': 'convulsions', 'type': 'Disease', 'start': 907, 'end': 918, 'mesh': 'D012640'}, {'text': 'bepridil', 'type': 'Chemical', 'start': 957, 'end': 965, 'mesh': 'D015764'}]"
+281,10091617,Selegiline-induced postural hypotension in Parkinson's disease: a longitudinal study on the effects of drug withdrawal.,"OBJECTIVES: The United Kingdom Parkinson's Disease Research Group (UKPDRG) trial found an increased mortality in patients with Parkinson's disease (PD) randomized to receive 10 mg selegiline per day and L-dopa compared with those taking L-dopa alone. Recently, we found that therapy with selegiline and L-dopa was associated with selective systolic orthostatic hypotension which was abolished by withdrawal of selegiline. This unwanted effect on postural blood pressure was not the result of underlying autonomic failure. The aims of this study were to confirm our previous findings in a separate cohort of patients and to determine the time course of the cardiovascular consequences of stopping selegiline in the expectation that this might shed light on the mechanisms by which the drug causes orthostatic hypotension. METHODS: The cardiovascular responses to standing and head-up tilt were studied repeatedly in PD patients receiving selegiline and as the drug was withdrawn. RESULTS: Head-up tilt caused systolic orthostatic hypotension which was marked in six of 20 PD patients on selegiline, one of whom lost consciousness with unrecordable blood pressures. A lesser degree of orthostatic hypotension occurred with standing. Orthostatic hypotension was ameliorated 4 days after withdrawal of selegiline and totally abolished 7 days after discontinuation of the drug. Stopping selegiline also significantly reduced the supine systolic and diastolic blood pressures consistent with a previously undescribed supine pressor action. CONCLUSION: This study confirms our previous finding that selegiline in combination with L-dopa is associated with selective orthostatic hypotension. The possibilities that these cardiovascular findings might be the result of non-selective inhibition of monoamine oxidase or of amphetamine and metamphetamine are discussed.","[{'text': 'Selegiline', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D012642'}, {'text': 'postural hypotension', 'type': 'Disease', 'start': 19, 'end': 39, 'mesh': 'D007024'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 43, 'end': 62, 'mesh': 'D010300'}, {'text': ""Parkinson's Disease"", 'type': 'Disease', 'start': 151, 'end': 170, 'mesh': 'D010300'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 247, 'end': 266, 'mesh': 'D010300'}, {'text': 'PD', 'type': 'Disease', 'start': 268, 'end': 270, 'mesh': 'D010300'}, {'text': 'selegiline', 'type': 'Chemical', 'start': 300, 'end': 310, 'mesh': 'D012642'}, {'text': 'L-dopa', 'type': 'Chemical', 'start': 323, 'end': 329, 'mesh': 'D007980'}, {'text': 'L-dopa', 'type': 'Chemical', 'start': 357, 'end': 363, 'mesh': 'D007980'}, {'text': 'selegiline', 'type': 'Chemical', 'start': 408, 'end': 418, 'mesh': 'D012642'}, {'text': 'L-dopa', 'type': 'Chemical', 'start': 423, 'end': 429, 'mesh': 'D007980'}, {'text': 'systolic orthostatic hypotension', 'type': 'Disease', 'start': 460, 'end': 492, 'mesh': 'D007024'}, {'text': 'selegiline', 'type': 'Chemical', 'start': 530, 'end': 540, 'mesh': 'D012642'}, {'text': 'selegiline', 'type': 'Chemical', 'start': 816, 'end': 826, 'mesh': 'D012642'}, {'text': 'orthostatic hypotension', 'type': 'Disease', 'start': 916, 'end': 939, 'mesh': 'D007024'}, {'text': 'PD', 'type': 'Disease', 'start': 1035, 'end': 1037, 'mesh': 'D010300'}, {'text': 'selegiline', 'type': 'Chemical', 'start': 1057, 'end': 1067, 'mesh': 'D012642'}, {'text': 'systolic orthostatic hypotension', 'type': 'Disease', 'start': 1128, 'end': 1160, 'mesh': 'D007024'}, {'text': 'PD', 'type': 'Disease', 'start': 1191, 'end': 1193, 'mesh': 'D010300'}, {'text': 'selegiline', 'type': 'Chemical', 'start': 1206, 'end': 1216, 'mesh': 'D012642'}, {'text': 'orthostatic hypotension', 'type': 'Disease', 'start': 1303, 'end': 1326, 'mesh': 'D007024'}, {'text': 'Orthostatic hypotension', 'type': 'Disease', 'start': 1351, 'end': 1374, 'mesh': 'D007024'}, {'text': 'selegiline', 'type': 'Chemical', 'start': 1418, 'end': 1428, 'mesh': 'D012642'}, {'text': 'selegiline', 'type': 'Chemical', 'start': 1502, 'end': 1512, 'mesh': 'D012642'}, {'text': 'reduced the supine systolic and diastolic blood pressures', 'type': 'Disease', 'start': 1532, 'end': 1589, 'mesh': 'D007024'}, {'text': 'selegiline', 'type': 'Chemical', 'start': 1712, 'end': 1722, 'mesh': 'D012642'}, {'text': 'L-dopa', 'type': 'Chemical', 'start': 1743, 'end': 1749, 'mesh': 'D007980'}, {'text': 'orthostatic hypotension', 'type': 'Disease', 'start': 1779, 'end': 1802, 'mesh': 'D007024'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1932, 'end': 1943, 'mesh': 'D000661'}, {'text': 'metamphetamine', 'type': 'Chemical', 'start': 1948, 'end': 1962, 'mesh': 'D008694'}]"
+282,19269743,Explicit episodic memory for sensory-discriminative components of capsaicin-induced pain: immediate and delayed ratings.,"Pain memory is thought to affect future pain sensitivity and thus contribute to clinical pain conditions. Systematic investigations of the human capacity to remember sensory features of experimental pain are sparse. In order to address long-term pain memory, nine healthy male volunteers received intradermal injections of three doses of capsaicin (0.05, 1 and 20 microg, separated by 15 min breaks), each given three times in a balanced design across three sessions at one week intervals. Pain rating was performed using a computerized visual analogue scale (0-100) digitized at 1/s, either immediately online or one hour or one day after injection. Subjects also recalled their pains one week later. Capsaicin injection reliably induced a dose-dependent flare (p<0.001) without any difference within or across sessions. The strong burning pain decayed exponentially within a few minutes. Subjects were able to reliably discriminate pain magnitude and duration across capsaicin doses (both p<0.001), regardless of whether first-time ratings were requested immediately, after one hour or after one day. Pain recall after one week was similarly precise (magnitude: p<0.01, duration: p<0.05). Correlation with rating recall after one week was best when first-time ratings were requested as late as one day after injection (R(2)=0.79) indicating that both rating retrievals utilized similar memory traces. These results indicate a reliable memory for magnitude and duration of experimentally induced pain. The data further suggest that the consolidation of this memory is an important interim stage, and may take up to one day.","[{'text': 'capsaicin', 'type': 'Chemical', 'start': 66, 'end': 75, 'mesh': 'D002211'}, {'text': 'pain', 'type': 'Disease', 'start': 84, 'end': 88, 'mesh': 'D010146'}, {'text': 'Pain', 'type': 'Disease', 'start': 121, 'end': 125, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 161, 'end': 165, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 210, 'end': 214, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 320, 'end': 324, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 367, 'end': 371, 'mesh': 'D010146'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 459, 'end': 468, 'mesh': 'D002211'}, {'text': 'Pain', 'type': 'Disease', 'start': 611, 'end': 615, 'mesh': 'D010146'}, {'text': 'pains', 'type': 'Disease', 'start': 801, 'end': 806, 'mesh': 'D010146'}, {'text': 'Capsaicin', 'type': 'Chemical', 'start': 823, 'end': 832, 'mesh': 'D002211'}, {'text': 'pain', 'type': 'Disease', 'start': 962, 'end': 966, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 1055, 'end': 1059, 'mesh': 'D010146'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 1090, 'end': 1099, 'mesh': 'D002211'}, {'text': 'Pain', 'type': 'Disease', 'start': 1224, 'end': 1228, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 1618, 'end': 1622, 'mesh': 'D010146'}]"
+283,3070035,Reversibility of captopril-induced renal insufficiency after prolonged use in an unusual case of renovascular hypertension.,"We report a case of severe hypertension with an occluded renal artery to a solitary kidney, who developed sudden deterioration of renal function following treatment with captopril. His renal function remained impaired but stable during 2 years' treatment with captopril but returned to pre-treatment levels soon after cessation of the drug. This indicates reversibility in captopril-induced renal failure even after its prolonged use and suggests that no organic damage occurs to glomerular arterioles following chronic ACE inhibition.","[{'text': 'captopril', 'type': 'Chemical', 'start': 17, 'end': 26, 'mesh': 'D002216'}, {'text': 'renal insufficiency', 'type': 'Disease', 'start': 35, 'end': 54, 'mesh': 'D051437'}, {'text': 'renovascular hypertension', 'type': 'Disease', 'start': 97, 'end': 122, 'mesh': 'D006978'}, {'text': 'hypertension', 'type': 'Disease', 'start': 151, 'end': 163, 'mesh': 'D006973'}, {'text': 'sudden deterioration of renal function', 'type': 'Disease', 'start': 230, 'end': 268, 'mesh': 'D058186'}, {'text': 'captopril', 'type': 'Chemical', 'start': 294, 'end': 303, 'mesh': 'D002216'}, {'text': 'captopril', 'type': 'Chemical', 'start': 384, 'end': 393, 'mesh': 'D002216'}, {'text': 'captopril', 'type': 'Chemical', 'start': 497, 'end': 506, 'mesh': 'D002216'}, {'text': 'renal failure', 'type': 'Disease', 'start': 515, 'end': 528, 'mesh': 'D051437'}]"
+284,1147734,Liver disease caused by propylthiouracil.,"This report presents the clinical, laboratory, and light and electron microscopic observations on a patient with chronic active (aggressive) hepatitis caused by the administration of propylthiouracil. This is an addition to the list of drugs that must be considered in the evaluation of chronic liver disease.","[{'text': 'Liver disease', 'type': 'Disease', 'start': 0, 'end': 13, 'mesh': 'D008107'}, {'text': 'propylthiouracil', 'type': 'Chemical', 'start': 24, 'end': 40, 'mesh': 'D011441'}, {'text': 'chronic active (aggressive) hepatitis', 'type': 'Disease', 'start': 155, 'end': 192, 'mesh': 'D006521'}, {'text': 'propylthiouracil', 'type': 'Chemical', 'start': 225, 'end': 241, 'mesh': 'D011441'}, {'text': 'liver disease', 'type': 'Disease', 'start': 337, 'end': 350, 'mesh': 'D008107'}]"
+285,12202650,Capsaicin-induced muscle pain alters the excitability of the human jaw-stretch reflex.,"The pathophysiology of painful temporomandibular disorders is not fully understood, but evidence suggests that muscle pain modulates motor function in characteristic ways. This study tested the hypothesis that activation of nociceptive muscle afferent fibers would be linked to an increased excitability of the human jaw-stretch reflex and whether this process would be sensitive to length and velocity of the stretch. Capsaicin (10 micro g) was injected into the masseter muscle to induce pain in 11 healthy volunteers. Short-latency reflex responses were evoked in the masseter and temporalis muscles by a stretch device with different velocities and displacements before, during, and after the pain. The normalized reflex amplitude increased with an increase in velocity at a given displacement, but remained constant with different displacements at a given velocity. The normalized reflex amplitude was significantly higher during pain, but only at faster stretches in the painful muscle. Increased sensitivity of the fusimotor system during acute muscle pain could be one likely mechanism to explain the findings.","[{'text': 'Capsaicin', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D002211'}, {'text': 'muscle pain', 'type': 'Disease', 'start': 18, 'end': 29, 'mesh': 'D063806'}, {'text': 'temporomandibular disorders', 'type': 'Disease', 'start': 118, 'end': 145, 'mesh': 'D013705'}, {'text': 'muscle pain', 'type': 'Disease', 'start': 198, 'end': 209, 'mesh': 'D063806'}, {'text': 'nociceptive muscle', 'type': 'Disease', 'start': 311, 'end': 329, 'mesh': 'D063806'}, {'text': 'Capsaicin', 'type': 'Chemical', 'start': 506, 'end': 515, 'mesh': 'D002211'}, {'text': 'pain', 'type': 'Disease', 'start': 577, 'end': 581, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 784, 'end': 788, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 1022, 'end': 1026, 'mesh': 'D010146'}, {'text': 'painful muscle', 'type': 'Disease', 'start': 1064, 'end': 1078, 'mesh': 'D063806'}, {'text': 'muscle pain', 'type': 'Disease', 'start': 1139, 'end': 1150, 'mesh': 'D063806'}]"
+286,18951540,Repetitive transcranial magnetic stimulation for levodopa-induced dyskinesias in Parkinson's disease.,"In a placebo-controlled, single-blinded, crossover study, we assessed the effect of ""real"" repetitive transcranial magnetic stimulation (rTMS) versus ""sham"" rTMS (placebo) on peak dose dyskinesias in patients with Parkinson's disease (PD). Ten patients with PD and prominent dyskinesias had rTMS (1,800 pulses; 1 Hz rate) delivered over the motor cortex for 4 consecutive days twice, once real stimuli and once sham stimulation were used; evaluations were done at the baseline and 1 day after the end of each of the treatment series. Direct comparison between sham and real rTMS effects showed no significant difference in clinician-assessed dyskinesia severity. However, comparison with the baseline showed small but significant reduction in dyskinesia severity following real rTMS but not placebo. The major effect was on dystonia subscore. Similarly, in patient diaries, although both treatments caused reduction in subjective dyskinesia scores during the days of intervention, the effect was sustained for 3 days after the intervention for the real rTMS only. Following rTMS, no side effects and no adverse effects on motor function and PD symptoms were noted. The results suggest the existence of residual beneficial clinical aftereffects of consecutive daily applications of low-frequency rTMS on dyskinesias in PD. The effects may be further exploited for potential therapeutic uses.","[{'text': 'levodopa', 'type': 'Chemical', 'start': 49, 'end': 57, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 66, 'end': 77, 'mesh': 'D004409'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 81, 'end': 100, 'mesh': 'D010300'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 287, 'end': 298, 'mesh': 'D004409'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 316, 'end': 335, 'mesh': 'D010300'}, {'text': 'PD', 'type': 'Disease', 'start': 337, 'end': 339, 'mesh': 'D010300'}, {'text': 'PD', 'type': 'Disease', 'start': 360, 'end': 362, 'mesh': 'D010300'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 377, 'end': 388, 'mesh': 'D004409'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 744, 'end': 754, 'mesh': 'D004409'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 845, 'end': 855, 'mesh': 'D004409'}, {'text': 'dystonia', 'type': 'Disease', 'start': 926, 'end': 934, 'mesh': 'D004421'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 1032, 'end': 1042, 'mesh': 'D004409'}, {'text': 'PD', 'type': 'Disease', 'start': 1243, 'end': 1245, 'mesh': 'D010300'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 1405, 'end': 1416, 'mesh': 'D004409'}, {'text': 'PD', 'type': 'Disease', 'start': 1420, 'end': 1422, 'mesh': 'D010300'}]"
+287,19657887,Disulfiram-like syndrome after hydrogen cyanamide professional skin exposure: two case reports in France.,"Hydrogen cyanamide is a plant growth regulator used in agriculture to induce bud break in fruit trees. Contact with the skin can result in percutaneous absorption of the substance that inhibits aldehyde dehydrogenase and can induce acetaldehyde syndrome in case of alcohol use. The purpose of this report is to describe two cases of a disulfiram-like syndrome following occupational exposure to hydrogen cyanamide. The first case involved a 59-year-old man who used Dormex, which contains hydrogen cyanamide, without protection after consuming a large amount of alcohol during a meal. In less than 1 hour after the ingestion of alcohol, he developed malaise with flushing of the face, tachycardia, and dyspnea. Manifestations regressed spontaneously under surveillance in the hospital. The second case occurred in a 55-year-old farmer following cutaneous contact with Dormex. Five hours after exposure, he developed disulfiram-like syndrome with flushing, tachycardia, and arterial hypotension after consuming three glasses of wine. The patient recovered spontaneously in 3 hours under surveillance in the hospital. These cases confirm the necessity of avoiding alcohol consumption as recommended in the instructions for use of Dormex and of preventing cutaneous contact during use.","[{'text': 'Disulfiram', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D004221'}, {'text': 'hydrogen cyanamide', 'type': 'Chemical', 'start': 31, 'end': 49, 'mesh': 'D003484'}, {'text': 'Hydrogen cyanamide', 'type': 'Chemical', 'start': 106, 'end': 124, 'mesh': 'D003484'}, {'text': 'aldehyde', 'type': 'Chemical', 'start': 300, 'end': 308, 'mesh': 'D000079'}, {'text': 'acetaldehyde', 'type': 'Chemical', 'start': 338, 'end': 350, 'mesh': 'D000079'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 371, 'end': 378, 'mesh': 'D000431'}, {'text': 'disulfiram', 'type': 'Chemical', 'start': 441, 'end': 451, 'mesh': 'D004221'}, {'text': 'hydrogen cyanamide', 'type': 'Chemical', 'start': 501, 'end': 519, 'mesh': 'D003484'}, {'text': 'Dormex', 'type': 'Chemical', 'start': 572, 'end': 578, 'mesh': 'D003484'}, {'text': 'hydrogen cyanamide', 'type': 'Chemical', 'start': 595, 'end': 613, 'mesh': 'D003484'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 668, 'end': 675, 'mesh': 'D000431'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 734, 'end': 741, 'mesh': 'D000431'}, {'text': 'flushing of the face', 'type': 'Disease', 'start': 769, 'end': 789, 'mesh': 'D005483'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 791, 'end': 802, 'mesh': 'D013610'}, {'text': 'dyspnea', 'type': 'Disease', 'start': 808, 'end': 815, 'mesh': 'D004417'}, {'text': 'Dormex', 'type': 'Chemical', 'start': 974, 'end': 980, 'mesh': 'D003484'}, {'text': 'disulfiram', 'type': 'Chemical', 'start': 1022, 'end': 1032, 'mesh': 'D004221'}, {'text': 'flushing', 'type': 'Disease', 'start': 1052, 'end': 1060, 'mesh': 'D005483'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 1062, 'end': 1073, 'mesh': 'D013610'}, {'text': 'arterial hypotension', 'type': 'Disease', 'start': 1079, 'end': 1099, 'mesh': 'D007022'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 1268, 'end': 1275, 'mesh': 'D000431'}, {'text': 'Dormex', 'type': 'Chemical', 'start': 1334, 'end': 1340, 'mesh': 'D003484'}]"
+288,9660111,Repeated trimipramine induces dopamine D2/D3 and alpha1-adrenergic up-regulation.,"Trimipramine (TRI), which shows a clinical antidepressant activity, is chemically related to imipramine but does not inhibit the reuptake of noradrenaline and 5-hydroxytryptamine, nor does it induce beta-adrenergic down-regulation. The mechanism of its antidepressant activity is still unknown. The aim of the present study was to find out whether TRI given repeatedly was able to induce adaptive changes in the dopaminergic and alpha1-adrenergic systems, demonstrated by us previously for various antidepressants. TRI was given to male Wistar rats and male Albino Swiss mice perorally twice daily for 14 days. In the acute experiment TRI (given i.p.) does not antagonize the reserpine hypothermia in mice and does not potentiate the 5-hydroxytryptophan head twitches in rats. TRI given repeatedly to rats increases the locomotor hyperactivity induced by d-amphetamine, quinpirole and (+)-7-hydroxy-dipropyloaminotetralin (dopamine D2 and D3 effects). The stereotypies induced by d-amphetamine or apomorphine are not potentiated by TRI. It increases the behaviour stimulation evoked by phenylephrine (given intraventricularly) in rats, evaluated in the open field test as well as the aggressiveness evoked by clonidine in mice, both these effects being mediated by an alpha1-adrenergic receptor. It may be concluded that, like other tricyclic antidepressants studied previously, TRI given repeatedly increases the responsiveness of brain dopamine D2 and D3 (locomotor activity but not stereotypy) as well as alpha1-adrenergic receptors to their agonists. A question arises whether the reuptake inhibition is of any importance to the adaptive changes induced by repeated antidepressants, suggested to be responsible for the antidepressant activity.","[{'text': 'trimipramine', 'type': 'Chemical', 'start': 9, 'end': 21, 'mesh': 'D014299'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 30, 'end': 38, 'mesh': 'D004298'}, {'text': 'Trimipramine', 'type': 'Chemical', 'start': 82, 'end': 94, 'mesh': 'D014299'}, {'text': 'TRI', 'type': 'Chemical', 'start': 96, 'end': 99, 'mesh': 'D014299'}, {'text': 'antidepressant', 'type': 'Chemical', 'start': 125, 'end': 139, 'mesh': 'D000928'}, {'text': 'imipramine', 'type': 'Chemical', 'start': 175, 'end': 185, 'mesh': 'D007099'}, {'text': 'noradrenaline', 'type': 'Chemical', 'start': 223, 'end': 236, 'mesh': 'D009638'}, {'text': '5-hydroxytryptamine', 'type': 'Chemical', 'start': 241, 'end': 260, 'mesh': 'D012701'}, {'text': 'antidepressant', 'type': 'Chemical', 'start': 335, 'end': 349, 'mesh': 'D000928'}, {'text': 'TRI', 'type': 'Chemical', 'start': 430, 'end': 433, 'mesh': 'D014299'}, {'text': 'antidepressants', 'type': 'Chemical', 'start': 580, 'end': 595, 'mesh': 'D000928'}, {'text': 'TRI', 'type': 'Chemical', 'start': 597, 'end': 600, 'mesh': 'D014299'}, {'text': 'TRI', 'type': 'Chemical', 'start': 717, 'end': 720, 'mesh': 'D014299'}, {'text': 'reserpine', 'type': 'Chemical', 'start': 758, 'end': 767, 'mesh': 'D012110'}, {'text': 'hypothermia', 'type': 'Disease', 'start': 768, 'end': 779, 'mesh': 'D007035'}, {'text': '5-hydroxytryptophan', 'type': 'Chemical', 'start': 816, 'end': 835, 'mesh': 'D006916'}, {'text': 'TRI', 'type': 'Chemical', 'start': 859, 'end': 862, 'mesh': 'D014299'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 912, 'end': 925, 'mesh': 'D006948'}, {'text': 'd-amphetamine', 'type': 'Chemical', 'start': 937, 'end': 950, 'mesh': 'D003913'}, {'text': 'quinpirole', 'type': 'Chemical', 'start': 952, 'end': 962, 'mesh': 'D019257'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1005, 'end': 1013, 'mesh': 'D004298'}, {'text': 'd-amphetamine', 'type': 'Chemical', 'start': 1062, 'end': 1075, 'mesh': 'D003913'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 1079, 'end': 1090, 'mesh': 'D001058'}, {'text': 'TRI', 'type': 'Chemical', 'start': 1114, 'end': 1117, 'mesh': 'D014299'}, {'text': 'phenylephrine', 'type': 'Chemical', 'start': 1168, 'end': 1181, 'mesh': 'D010656'}, {'text': 'aggressiveness', 'type': 'Disease', 'start': 1266, 'end': 1280, 'mesh': 'D010554'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 1291, 'end': 1300, 'mesh': 'D003000'}, {'text': 'antidepressants', 'type': 'Chemical', 'start': 1425, 'end': 1440, 'mesh': 'D000928'}, {'text': 'TRI', 'type': 'Chemical', 'start': 1461, 'end': 1464, 'mesh': 'D014299'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1520, 'end': 1528, 'mesh': 'D004298'}, {'text': 'antidepressants', 'type': 'Chemical', 'start': 1752, 'end': 1767, 'mesh': 'D000928'}, {'text': 'antidepressant', 'type': 'Chemical', 'start': 1805, 'end': 1819, 'mesh': 'D000928'}]"
+289,11431197,Ranitidine-induced acute interstitial nephritis in a cadaveric renal allograft.,"Ranitidine frequently is used for preventing peptic ulceration after renal transplantation. This drug occasionally has been associated with acute interstitial nephritis in native kidneys. There are no similar reports with renal transplantation. We report a case of ranitidine-induced acute interstitial nephritis in a recipient of a cadaveric renal allograft presenting with acute allograft dysfunction within 48 hours of exposure to the drug. The biopsy specimen showed pathognomonic features, including eosinophilic infiltration of the interstitial compartment. Allograft function improved rapidly and returned to baseline after stopping the drug.","[{'text': 'Ranitidine', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D011899'}, {'text': 'interstitial nephritis', 'type': 'Disease', 'start': 25, 'end': 47, 'mesh': 'D009395'}, {'text': 'Ranitidine', 'type': 'Chemical', 'start': 80, 'end': 90, 'mesh': 'D011899'}, {'text': 'interstitial nephritis', 'type': 'Disease', 'start': 226, 'end': 248, 'mesh': 'D009395'}, {'text': 'ranitidine', 'type': 'Chemical', 'start': 345, 'end': 355, 'mesh': 'D011899'}, {'text': 'interstitial nephritis', 'type': 'Disease', 'start': 370, 'end': 392, 'mesh': 'D009395'}]"
+290,7449470,"Late, late doxorubicin cardiotoxicity.","Cardiac toxicity is a major complication which limits the use of adriamycin as a chemotherapeutic agent. Cardiomyopathy is frequent when the total dose exceeds 600 mg/m2 and occurs within one to six months after cessation of therapy. A patient is reported who developed progressive cardiomyopathy two and one-half years after receiving 580 mg/m2 which apparently represents late, late cardiotoxicity.","[{'text': 'doxorubicin', 'type': 'Chemical', 'start': 11, 'end': 22, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 23, 'end': 37, 'mesh': 'D066126'}, {'text': 'Cardiac toxicity', 'type': 'Disease', 'start': 39, 'end': 55, 'mesh': 'D066126'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 104, 'end': 114, 'mesh': 'D004317'}, {'text': 'Cardiomyopathy', 'type': 'Disease', 'start': 144, 'end': 158, 'mesh': 'D009202'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 321, 'end': 335, 'mesh': 'D009202'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 424, 'end': 438, 'mesh': 'D066126'}]"
+291,8170551,Acetazolamide-induced nephrolithiasis: implications for treatment of neuromuscular disorders.,"Carbonic anhydrase inhibitors can cause nephrolithiasis. We studied 20 patients receiving long-term carbonic anhydrase inhibitor treatment for periodic paralysis and myotonia. Three patients on acetazolamide (15%) developed renal calculi. Extracorporeal lithotripsy successfully removed a renal calculus in one patient and surgery removed a staghorn calculus in another, permitting continued treatment. Renal function remained normal in all patients. Nephrolithiasis is a complication of acetazolamide but does not preclude its use.","[{'text': 'Acetazolamide', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'D000086'}, {'text': 'nephrolithiasis', 'type': 'Disease', 'start': 22, 'end': 37, 'mesh': 'D053040'}, {'text': 'neuromuscular disorders', 'type': 'Disease', 'start': 69, 'end': 92, 'mesh': 'D009468'}, {'text': 'nephrolithiasis', 'type': 'Disease', 'start': 134, 'end': 149, 'mesh': 'D053040'}, {'text': 'paralysis', 'type': 'Disease', 'start': 246, 'end': 255, 'mesh': 'D010243'}, {'text': 'myotonia', 'type': 'Disease', 'start': 260, 'end': 268, 'mesh': 'D009222'}, {'text': 'acetazolamide', 'type': 'Chemical', 'start': 288, 'end': 301, 'mesh': 'D000086'}, {'text': 'renal calculi', 'type': 'Disease', 'start': 318, 'end': 331, 'mesh': 'D007669'}, {'text': 'renal calculus', 'type': 'Disease', 'start': 383, 'end': 397, 'mesh': 'D007669'}, {'text': 'calculus', 'type': 'Disease', 'start': 444, 'end': 452, 'mesh': 'D002137'}, {'text': 'Nephrolithiasis', 'type': 'Disease', 'start': 545, 'end': 560, 'mesh': 'D053040'}, {'text': 'acetazolamide', 'type': 'Chemical', 'start': 582, 'end': 595, 'mesh': 'D000086'}]"
+292,2476560,Is the treatment of scabies hazardous?,"Treatment for scabies is usually initiated by general practitioners; most consider lindane (gamma benzene hexachloride) the treatment of choice. Lindane is also widely used as an agricultural and industrial pesticide, and as a result the toxic profile of this insecticide is well understood. Evidence is accumulating that lindane can be toxic to the central nervous system and may be associated with aplastic anaemia. Preparations containing lindane continue to be sold over the counter and may represent a hazard to poorly informed patients. This literature review suggests that general practitioners should prescribe scabicides with increased caution for certain at-risk groups, and give adequate warnings regarding potential toxicity.","[{'text': 'scabies', 'type': 'Disease', 'start': 20, 'end': 27, 'mesh': 'D012532'}, {'text': 'scabies', 'type': 'Disease', 'start': 53, 'end': 60, 'mesh': 'D012532'}, {'text': 'lindane', 'type': 'Chemical', 'start': 122, 'end': 129, 'mesh': 'D001556'}, {'text': 'gamma benzene hexachloride', 'type': 'Chemical', 'start': 131, 'end': 157, 'mesh': 'D001556'}, {'text': 'Lindane', 'type': 'Chemical', 'start': 184, 'end': 191, 'mesh': 'D001556'}, {'text': 'lindane', 'type': 'Chemical', 'start': 361, 'end': 368, 'mesh': 'D001556'}, {'text': 'toxic to the central nervous system', 'type': 'Disease', 'start': 376, 'end': 411, 'mesh': 'D002493'}, {'text': 'aplastic anaemia', 'type': 'Disease', 'start': 439, 'end': 455, 'mesh': 'D000741'}, {'text': 'lindane', 'type': 'Chemical', 'start': 481, 'end': 488, 'mesh': 'D001556'}, {'text': 'toxicity', 'type': 'Disease', 'start': 767, 'end': 775, 'mesh': 'D064420'}]"
+293,19803309,Anaesthetists' nightmare: masseter spasm after induction in an undiagnosed case of myotonia congenita.,"We report an undiagnosed case of myotonia congenita in a 24-year-old previously healthy primigravida, who developed life threatening masseter spasm following a standard dose of intravenous suxamethonium for induction of anaesthesia. Neither the patient nor the anaesthetist was aware of the diagnosis before this potentially lethal complication occurred.","[{'text': 'masseter spasm', 'type': 'Disease', 'start': 26, 'end': 40, 'mesh': 'D014313'}, {'text': 'myotonia congenita', 'type': 'Disease', 'start': 83, 'end': 101, 'mesh': 'D009224'}, {'text': 'myotonia congenita', 'type': 'Disease', 'start': 136, 'end': 154, 'mesh': 'D009224'}, {'text': 'masseter spasm', 'type': 'Disease', 'start': 236, 'end': 250, 'mesh': 'D014313'}, {'text': 'suxamethonium', 'type': 'Chemical', 'start': 292, 'end': 305, 'mesh': 'D013390'}]"
+294,18821488,Toxicity in rhesus monkeys following administration of the 8-aminoquinoline 8-[(4-amino-l-methylbutyl)amino]- 5-(l-hexyloxy)-6-methoxy-4-methylquinoline (WR242511).,"INTRODUCTION: Many substances that form methemoglobin (MHb) effectively counter cyanide (CN) toxicity. Although MHb formers are generally applied as treatments for CN poisoning, it has been proposed that a stable, long-acting MHb former could serve as a CN pretreatment. Using this rationale, the 8-aminoquinoline WR242511, a potent long-lasting MHb former in rodents and beagle dogs, was studied in the rhesus monkey for advanced development as a potential CN pretreatment. METHODS: In this study, WR242511 was administered intravenously (IV) in 2 female and 4 male rhesus monkeys in doses of 3.5 and/or 7.0 mg/kg; a single male also received WR242511 orally (PO) at 7.0 mg/kg. Health status and MHb levels were monitored following exposure. RESULTS: The selected doses of WR242511, which produced significant methemoglobinemia in beagle dogs in earlier studies conducted elsewhere, produced very little MHb (mean < 2.0%) in the rhesus monkey. Furthermore, transient hemoglobinuria was noted approximately 60 minutes postinjection of WR242511 (3.5 or 7.0 mg/kg), and 2 lethalities occurred (one IV and one PO) following the 7.0 mg/kg dose. Myoglobinuria was also observed following the 7.0 mg/kg dose. Histopathology analyses in the 2 animals that died revealed liver and kidney toxicity, with greater severity in the orally-treated animal. CONCLUSIONS: These data demonstrate direct and/or indirect drug-induced toxicity. It is concluded that WR242511 should not be pursued as a pretreatment for CN poisoning unless the anti-CN characteristics of this compound can be successfully dissociated from those producing undesirable toxicity.","[{'text': 'Toxicity', 'type': 'Disease', 'start': 0, 'end': 8, 'mesh': 'D064420'}, {'text': '8-aminoquinoline', 'type': 'Chemical', 'start': 59, 'end': 75, 'mesh': 'C080436'}, {'text': '8-[(4-amino-l-methylbutyl)amino]- 5-(l-hexyloxy)-6-methoxy-4-methylquinoline', 'type': 'Chemical', 'start': 76, 'end': 152, 'mesh': 'C068820'}, {'text': 'WR242511', 'type': 'Chemical', 'start': 154, 'end': 162, 'mesh': 'C068820'}, {'text': 'toxicity', 'type': 'Disease', 'start': 258, 'end': 266, 'mesh': 'D064420'}, {'text': 'poisoning', 'type': 'Disease', 'start': 332, 'end': 341, 'mesh': 'D011041'}, {'text': '8-aminoquinoline', 'type': 'Chemical', 'start': 462, 'end': 478, 'mesh': 'C080436'}, {'text': 'WR242511', 'type': 'Chemical', 'start': 479, 'end': 487, 'mesh': 'C068820'}, {'text': 'WR242511', 'type': 'Chemical', 'start': 664, 'end': 672, 'mesh': 'C068820'}, {'text': 'WR242511', 'type': 'Chemical', 'start': 809, 'end': 817, 'mesh': 'C068820'}, {'text': 'WR242511', 'type': 'Chemical', 'start': 939, 'end': 947, 'mesh': 'C068820'}, {'text': 'methemoglobinemia', 'type': 'Disease', 'start': 976, 'end': 993, 'mesh': 'D008708'}, {'text': 'hemoglobinuria', 'type': 'Disease', 'start': 1133, 'end': 1147, 'mesh': 'D006456'}, {'text': 'WR242511', 'type': 'Chemical', 'start': 1200, 'end': 1208, 'mesh': 'C068820'}, {'text': 'Myoglobinuria', 'type': 'Disease', 'start': 1306, 'end': 1319, 'mesh': 'D009212'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1579, 'end': 1587, 'mesh': 'D064420'}, {'text': 'WR242511', 'type': 'Chemical', 'start': 1610, 'end': 1618, 'mesh': 'C068820'}, {'text': 'poisoning', 'type': 'Disease', 'start': 1666, 'end': 1675, 'mesh': 'D011041'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1793, 'end': 1801, 'mesh': 'D064420'}]"
+295,8372922,Neuroplasticity of the adult primate auditory cortex following cochlear hearing loss.,"Tonotopic organization is an essential feature of the primary auditory area (A1) of primate cortex. In A1 of macaque monkeys, low frequencies are represented rostrolaterally and high frequencies are represented caudomedially. The purpose of this study was to determine if changes occur in this tonotopic organization following cochlear hearing loss. Under anesthesia, the superior temporal gyrus of adult macaque monkeys was exposed, and the tonotopic organization of A1 was mapped using conventional microelectrode recording techniques. Following recovery, the monkeys were selectively deafened for high frequencies using kanamycin and furosemide. The actual frequencies deafened were determined by the loss of tone-burst elicited auditory brainstem responses. Three months after deafening, A1 was remapped. Postmortem cytoarchitectural features identifying A1 were correlated with the electrophysiologic data. The results indicate that the deprived area of A1 undergoes extensive reorganization and becomes responsive to intact cochlear frequencies. The region of cortex that represents the low frequencies was not obviously affected by the cochlear hearing loss.","[{'text': 'hearing loss', 'type': 'Disease', 'start': 72, 'end': 84, 'mesh': 'D034381'}, {'text': 'hearing loss', 'type': 'Disease', 'start': 422, 'end': 434, 'mesh': 'D034381'}, {'text': 'kanamycin', 'type': 'Chemical', 'start': 709, 'end': 718, 'mesh': 'D007612'}, {'text': 'furosemide', 'type': 'Chemical', 'start': 723, 'end': 733, 'mesh': 'D005665'}, {'text': 'hearing loss', 'type': 'Disease', 'start': 1238, 'end': 1250, 'mesh': 'D034381'}]"
+296,9195768,The site of common side effects of sumatriptan.,"Atypical sensations following the use of subcutaneous sumatriptan are common, but of uncertain origin. They are almost always benign, but can be mistaken for a serious adverse event by the patient. Two patients are presented with tingling or burning sensations limited to areas of heat exposure or sunburn. In these individuals, side effects are most likely generated superficially in the skin.","[{'text': 'sumatriptan', 'type': 'Chemical', 'start': 35, 'end': 46, 'mesh': 'D018170'}, {'text': 'Atypical sensations', 'type': 'Disease', 'start': 48, 'end': 67, 'mesh': 'D010292'}, {'text': 'sumatriptan', 'type': 'Chemical', 'start': 102, 'end': 113, 'mesh': 'D018170'}, {'text': 'tingling or burning sensations', 'type': 'Disease', 'start': 278, 'end': 308, 'mesh': 'D010292'}, {'text': 'sunburn', 'type': 'Disease', 'start': 346, 'end': 353, 'mesh': 'D013471'}]"
+297,15338796,"Tremor side effects of salbutamol, quantified by a laser pointer technique.","OBJECTIVE: To study tremor side effects of salbutamol an easily applicable, quick and low-priced method is needed. A new method using a commercially available, pen-shaped laser pointer was developed. Aim of the study was to determine sensitivity, reproducibility, reference values and the agreement with a questionnaire. METHODS: Tremor was measured using a laser pointer technique. To determine sensitivity we assessed tremor in 44 patients with obstructive lung disease after administration of cumulative doses of salbutamol. Subjects were asked to aim at the centre of a target, subdivided in concentric circles, from 5 m distance. The circle in which the participant succeeded to aim was recorded in millimetres radius. In another series of measurements, reproducibility and reference values of the tremor was assessed in 65 healthy subjects in three sessions, at 9 a.m., 4 p.m. and 9 a.m., respectively, 1 week later. Postural tremor was measured with the arm horizontally outstretched rest tremor with the arm supported by an armrest and finally tremor was measured after holding a 2-kg weight until exhaustion. Inter-observer variability was measured in a series of 10 healthy subjects. Tremor was measured simultaneously by two independent observers. RESULTS: Salbutamol significantly increased tremor severity in patients in a dose-dependent way. Within healthy adults no age-dependency could be found (b = 0.262 mm/year; P = 0.72). There was no agreement between the questionnaire and tremor severity (r = 0.093; P = 0.53). Postural tremor showed no significant difference between the first and third session (P = 0.07). Support of the arm decreased tremor severity, exhaustion increased tremor severity significantly. A good agreement was found between two independent observers (interclass correlation coefficient 0.72). DISCUSSION: Quantifying tremor by using an inexpensive laser pointer is, with the exception of children (<12 years) a sensitive and reproducible method.","[{'text': 'Tremor', 'type': 'Disease', 'start': 0, 'end': 6, 'mesh': 'D014202'}, {'text': 'salbutamol', 'type': 'Chemical', 'start': 23, 'end': 33, 'mesh': 'D000420'}, {'text': 'tremor', 'type': 'Disease', 'start': 96, 'end': 102, 'mesh': 'D014202'}, {'text': 'salbutamol', 'type': 'Chemical', 'start': 119, 'end': 129, 'mesh': 'D000420'}, {'text': 'Tremor', 'type': 'Disease', 'start': 406, 'end': 412, 'mesh': 'D014202'}, {'text': 'tremor', 'type': 'Disease', 'start': 496, 'end': 502, 'mesh': 'D014202'}, {'text': 'obstructive lung disease', 'type': 'Disease', 'start': 523, 'end': 547, 'mesh': 'D008173'}, {'text': 'salbutamol', 'type': 'Chemical', 'start': 592, 'end': 602, 'mesh': 'D000420'}, {'text': 'tremor', 'type': 'Disease', 'start': 879, 'end': 885, 'mesh': 'D014202'}, {'text': 'tremor', 'type': 'Disease', 'start': 1008, 'end': 1014, 'mesh': 'D014202'}, {'text': 'tremor', 'type': 'Disease', 'start': 1072, 'end': 1078, 'mesh': 'D014202'}, {'text': 'tremor', 'type': 'Disease', 'start': 1128, 'end': 1134, 'mesh': 'D014202'}, {'text': 'Tremor', 'type': 'Disease', 'start': 1270, 'end': 1276, 'mesh': 'D014202'}, {'text': 'Salbutamol', 'type': 'Chemical', 'start': 1344, 'end': 1354, 'mesh': 'D000420'}, {'text': 'tremor', 'type': 'Disease', 'start': 1379, 'end': 1385, 'mesh': 'D014202'}, {'text': 'tremor', 'type': 'Disease', 'start': 1571, 'end': 1577, 'mesh': 'D014202'}, {'text': 'tremor', 'type': 'Disease', 'start': 1619, 'end': 1625, 'mesh': 'D014202'}, {'text': 'tremor', 'type': 'Disease', 'start': 1736, 'end': 1742, 'mesh': 'D014202'}, {'text': 'tremor', 'type': 'Disease', 'start': 1774, 'end': 1780, 'mesh': 'D014202'}, {'text': 'tremor', 'type': 'Disease', 'start': 1933, 'end': 1939, 'mesh': 'D014202'}]"
+298,12627929,Increased frequency of venous thromboembolism with the combination of docetaxel and thalidomide in patients with metastatic androgen-independent prostate cancer.,"STUDY OBJECTIVE: To evaluate the frequency of venous thromboembolism (VTE) in patients with advanced androgen-independent prostate cancer who were treated with docetaxel alone or in combination with thalidomide. DESIGN: Retrospective analysis of a randomized phase II trial. SETTING: National Institutes of Health clinical research center. PATIENTS: Seventy men, aged 50-80 years, with advanced androgen-independent prostate cancer. INTERVENTION: Each patient received either intravenous docetaxel 30 mg/m2/week for 3 consecutive weeks, followed by 1 week off, or the combination of continuous oral thalidomide 200 mg every evening plus the same docetaxel regimen. This 4-week cycle was repeated until there was evidence of excessive toxicity or disease progression. MEASUREMENTS AND MAIN RESULTS: None of 23 patients who received docetaxel alone developed VTE, whereas 9 of 47 patients (19%) who received docetaxel plus thalidomide developed VTE (p=0.025). CONCLUSION: The addition of thalidomide to docetaxel in the treatment of prostate cancer significantly increases the frequency of VTE. Clinicians should be aware of this potential complication when adding thalidomide to chemotherapeutic regimens.","[{'text': 'venous thromboembolism', 'type': 'Disease', 'start': 23, 'end': 45, 'mesh': 'D054556'}, {'text': 'docetaxel', 'type': 'Chemical', 'start': 70, 'end': 79, 'mesh': 'C067311'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 84, 'end': 95, 'mesh': 'D013792'}, {'text': 'prostate cancer', 'type': 'Disease', 'start': 145, 'end': 160, 'mesh': 'D011471'}, {'text': 'venous thromboembolism', 'type': 'Disease', 'start': 208, 'end': 230, 'mesh': 'D054556'}, {'text': 'VTE', 'type': 'Disease', 'start': 232, 'end': 235, 'mesh': 'D054556'}, {'text': 'prostate cancer', 'type': 'Disease', 'start': 284, 'end': 299, 'mesh': 'D011471'}, {'text': 'docetaxel', 'type': 'Chemical', 'start': 322, 'end': 331, 'mesh': 'C067311'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 361, 'end': 372, 'mesh': 'D013792'}, {'text': 'prostate cancer', 'type': 'Disease', 'start': 578, 'end': 593, 'mesh': 'D011471'}, {'text': 'docetaxel', 'type': 'Chemical', 'start': 650, 'end': 659, 'mesh': 'C067311'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 761, 'end': 772, 'mesh': 'D013792'}, {'text': 'docetaxel', 'type': 'Chemical', 'start': 808, 'end': 817, 'mesh': 'C067311'}, {'text': 'toxicity', 'type': 'Disease', 'start': 896, 'end': 904, 'mesh': 'D064420'}, {'text': 'docetaxel', 'type': 'Chemical', 'start': 993, 'end': 1002, 'mesh': 'C067311'}, {'text': 'VTE', 'type': 'Disease', 'start': 1019, 'end': 1022, 'mesh': 'D054556'}, {'text': 'docetaxel', 'type': 'Chemical', 'start': 1068, 'end': 1077, 'mesh': 'C067311'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 1083, 'end': 1094, 'mesh': 'D013792'}, {'text': 'VTE', 'type': 'Disease', 'start': 1105, 'end': 1108, 'mesh': 'D054556'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 1148, 'end': 1159, 'mesh': 'D013792'}, {'text': 'docetaxel', 'type': 'Chemical', 'start': 1163, 'end': 1172, 'mesh': 'C067311'}, {'text': 'prostate cancer', 'type': 'Disease', 'start': 1193, 'end': 1208, 'mesh': 'D011471'}, {'text': 'VTE', 'type': 'Disease', 'start': 1250, 'end': 1253, 'mesh': 'D054556'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 1325, 'end': 1336, 'mesh': 'D013792'}]"
+299,6634932,"Sublingual absorption of the quaternary ammonium antiarrhythmic agent, UM-272.","UM-272 (N,N-dimethylpropranolol), a quaternary antiarrhythmic agent, was administered sublingually to dogs with ouabain-induced ventricular tachycardias. Both anti-arrhythmic efficacy and bioavailability were compared to oral drug. Sublingual UM-272 converted ventricular tachycardia to sinus rhythm in all 5 dogs. The area under the plasma concentration time curve at 90 min was 4-12 times greater than for oral drug, suggesting the existence of an absorption-limiting process in the intestine, and providing an alternate form of administration for quaternary drugs.","[{'text': 'quaternary ammonium', 'type': 'Chemical', 'start': 29, 'end': 48, 'mesh': 'D000644'}, {'text': 'UM-272', 'type': 'Chemical', 'start': 71, 'end': 77, 'mesh': 'C002616'}, {'text': 'UM-272', 'type': 'Chemical', 'start': 79, 'end': 85, 'mesh': 'C002616'}, {'text': 'N,N-dimethylpropranolol', 'type': 'Chemical', 'start': 87, 'end': 110, 'mesh': 'C002616'}, {'text': 'ouabain', 'type': 'Chemical', 'start': 191, 'end': 198, 'mesh': 'D010042'}, {'text': 'ventricular tachycardias', 'type': 'Disease', 'start': 207, 'end': 231, 'mesh': 'D017180'}, {'text': 'UM-272', 'type': 'Chemical', 'start': 322, 'end': 328, 'mesh': 'C002616'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 339, 'end': 362, 'mesh': 'D017180'}]"
+300,18791946,Severe thrombocytopenia and haemolytic anaemia associated with ciprofloxacin: a case report with fatal outcome.,"Haematological adverse reactions associated with fatal outcome are rare during treatment with ciprofloxacin. A 30-year old Caucasian man reported with abdominal pain and jaundice after 3-day administration of oral ciprofloxacin for a suspect of urinary tract infection. Clinical evaluations suggested an initial diagnosis of severe thrombocytopenia and haemolysis. The patient progressively developed petechiae and purpura on thorax and lower limbs. Despite pharmacological and supportive interventions, laboratory parameters worsened and the patient died 17 hours after admission. An accurate autopsy revealed most organs with diffuse petechial haemorrhages. No signs of bone marrow depression were found. No thrombi or signs of microangiopathies were observed in arterial vessels. Blood and urine cultures did not show any bacterial growth. This case report shows that ciprofloxacin may precipitate life-threatening thrombocytopenia and haemolytic anaemia, even in the early phases of treatment and without apparent previous exposures.","[{'text': 'thrombocytopenia', 'type': 'Disease', 'start': 7, 'end': 23, 'mesh': 'D013921'}, {'text': 'haemolytic anaemia', 'type': 'Disease', 'start': 28, 'end': 46, 'mesh': 'D000743'}, {'text': 'ciprofloxacin', 'type': 'Chemical', 'start': 63, 'end': 76, 'mesh': 'D002939'}, {'text': 'ciprofloxacin', 'type': 'Chemical', 'start': 206, 'end': 219, 'mesh': 'D002939'}, {'text': 'abdominal pain', 'type': 'Disease', 'start': 263, 'end': 277, 'mesh': 'D015746'}, {'text': 'jaundice', 'type': 'Disease', 'start': 282, 'end': 290, 'mesh': 'D007565'}, {'text': 'ciprofloxacin', 'type': 'Chemical', 'start': 326, 'end': 339, 'mesh': 'D002939'}, {'text': 'urinary tract infection', 'type': 'Disease', 'start': 357, 'end': 380, 'mesh': 'D014552'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 444, 'end': 460, 'mesh': 'D013921'}, {'text': 'haemolysis', 'type': 'Disease', 'start': 465, 'end': 475, 'mesh': 'D006461'}, {'text': 'petechiae', 'type': 'Disease', 'start': 513, 'end': 522, 'mesh': 'D011693'}, {'text': 'purpura', 'type': 'Disease', 'start': 527, 'end': 534, 'mesh': 'D011693'}, {'text': 'haemorrhages', 'type': 'Disease', 'start': 758, 'end': 770, 'mesh': 'D006470'}, {'text': 'bone marrow depression', 'type': 'Disease', 'start': 784, 'end': 806, 'mesh': 'D001855'}, {'text': 'thrombi', 'type': 'Disease', 'start': 822, 'end': 829, 'mesh': 'D013927'}, {'text': 'microangiopathies', 'type': 'Disease', 'start': 842, 'end': 859, 'mesh': 'D014652'}, {'text': 'ciprofloxacin', 'type': 'Chemical', 'start': 983, 'end': 996, 'mesh': 'D002939'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 1030, 'end': 1046, 'mesh': 'D013921'}, {'text': 'haemolytic anaemia', 'type': 'Disease', 'start': 1051, 'end': 1069, 'mesh': 'D000743'}]"
+301,17344566,Simvastatin-induced bilateral leg compartment syndrome and myonecrosis associated with hypothyroidism.,A 54-year-old hypothyroid male taking thyroxine and simvastatin presented with bilateral leg compartment syndrome and myonecrosis. Urgent fasciotomies were performed and the patient made an uneventful recovery with the withdrawal of simvastatin. It is likely that this complication will be seen more often with the increased worldwide use of this drug and its approval for all arteriopathic patients.,"[{'text': 'Simvastatin', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D019821'}, {'text': 'compartment syndrome', 'type': 'Disease', 'start': 34, 'end': 54, 'mesh': 'D003161'}, {'text': 'myonecrosis', 'type': 'Disease', 'start': 59, 'end': 70, 'mesh': 'D009135'}, {'text': 'hypothyroidism', 'type': 'Disease', 'start': 87, 'end': 101, 'mesh': 'D007037'}, {'text': 'hypothyroid', 'type': 'Disease', 'start': 117, 'end': 128, 'mesh': 'D007037'}, {'text': 'thyroxine', 'type': 'Chemical', 'start': 141, 'end': 150, 'mesh': 'D013974'}, {'text': 'simvastatin', 'type': 'Chemical', 'start': 155, 'end': 166, 'mesh': 'D019821'}, {'text': 'compartment syndrome', 'type': 'Disease', 'start': 196, 'end': 216, 'mesh': 'D003161'}, {'text': 'myonecrosis', 'type': 'Disease', 'start': 221, 'end': 232, 'mesh': 'D009135'}, {'text': 'simvastatin', 'type': 'Chemical', 'start': 336, 'end': 347, 'mesh': 'D019821'}, {'text': 'arteriopathic', 'type': 'Disease', 'start': 480, 'end': 493, 'mesh': 'D014652'}]"
+302,9293063,Bile duct hamartoma occurring in association with long-term treatment with danazol.,"We report a case of bile duct hamartoma which developed in a patient who had been on long-term danazol treatment. Such patients should be under close follow-up, preferably with periodic ultrasound examination of the liver. If the patient develops a liver mass, because of non-specific clinical features and imaging appearances, biopsy may be the only way to achieve a definitive diagnosis.","[{'text': 'danazol', 'type': 'Chemical', 'start': 75, 'end': 82, 'mesh': 'D003613'}, {'text': 'danazol', 'type': 'Chemical', 'start': 179, 'end': 186, 'mesh': 'D003613'}, {'text': 'liver mass', 'type': 'Disease', 'start': 333, 'end': 343, 'mesh': 'D008107'}]"
+303,1728522,Granulomatous hepatitis due to combination of amoxicillin and clavulanic acid.,"We report the case of a patient with amoxicillin-clavulanic acid-induced hepatitis with histologic multiple granulomas. This type of lesion broadens the spectrum of liver injury due to this drug combination, mainly represented by a benign cholestatic syndrome. The association of granulomas and eosinophilia favor an immunoallergic mechanism. As penicillin derivatives and amoxicillin alone are known to induce such types of lesions, the amoxicillin component, with or without a potentiating effect of clavulanic acid, might have a major role.","[{'text': 'combination of amoxicillin and clavulanic acid', 'type': 'Chemical', 'start': 31, 'end': 77, 'mesh': 'D019980'}, {'text': 'amoxicillin-clavulanic acid', 'type': 'Chemical', 'start': 116, 'end': 143, 'mesh': 'D019980'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 152, 'end': 161, 'mesh': 'D056486'}, {'text': 'granulomas', 'type': 'Disease', 'start': 187, 'end': 197, 'mesh': 'D006099'}, {'text': 'liver injury', 'type': 'Disease', 'start': 244, 'end': 256, 'mesh': 'D056486'}, {'text': 'cholestatic syndrome', 'type': 'Disease', 'start': 318, 'end': 338, 'mesh': 'D002779'}, {'text': 'granulomas', 'type': 'Disease', 'start': 359, 'end': 369, 'mesh': 'D006099'}, {'text': 'eosinophilia', 'type': 'Disease', 'start': 374, 'end': 386, 'mesh': 'D004802'}, {'text': 'penicillin', 'type': 'Chemical', 'start': 425, 'end': 435, 'mesh': 'D010406'}, {'text': 'amoxicillin', 'type': 'Chemical', 'start': 452, 'end': 463, 'mesh': 'D000658'}, {'text': 'amoxicillin', 'type': 'Chemical', 'start': 517, 'end': 528, 'mesh': 'D000658'}, {'text': 'clavulanic acid', 'type': 'Chemical', 'start': 581, 'end': 596, 'mesh': 'D019818'}]"
+304,10807237,Intracranial aneurysms and cocaine abuse: analysis of prognostic indicators.,"OBJECTIVE: The outcome of subarachnoid hemorrhage associated with cocaine abuse is reportedly poor. However, no study in the literature has reported the use of a statistical model to analyze the variables that influence outcome. METHODS: A review of admissions during a 6-year period revealed 14 patients with cocaine-related aneurysms. This group was compared with a control group of 135 patients with ruptured aneurysms and no history of cocaine abuse. Age at presentation, time of ictus after intoxication, Hunt and Hess grade of subarachnoid hemorrhage, size of the aneurysm, location of the aneurysm, and the Glasgow Outcome Scale score were assessed and compared. RESULTS: The patients in the study group were significantly younger than the patients in the control group (P < 0.002). In patients in the study group, all aneurysms were located in the anterior circulation. The majority of these aneurysms were smaller than those of the control group (8 +/- 6.08 mm versus 11 +/- 5.4 mm; P = 0.05). The differences in mortality and morbidity between the two groups were not significant. Hunt and Hess grade (P < 0.005) and age (P < 0.007) were significant predictors of outcome for the patients with cocaine-related aneurysms. CONCLUSION: Cocaine use predisposed aneurysmal rupture at a significantly earlier age and in much smaller aneurysms. Contrary to the published literature, this group did reasonably well with aggressive management.","[{'text': 'Intracranial aneurysms', 'type': 'Disease', 'start': 0, 'end': 22, 'mesh': 'D002532'}, {'text': 'cocaine abuse', 'type': 'Disease', 'start': 27, 'end': 40, 'mesh': 'D019970'}, {'text': 'subarachnoid hemorrhage', 'type': 'Disease', 'start': 103, 'end': 126, 'mesh': 'D013345'}, {'text': 'cocaine abuse', 'type': 'Disease', 'start': 143, 'end': 156, 'mesh': 'D019970'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 387, 'end': 394, 'mesh': 'D003042'}, {'text': 'aneurysms', 'type': 'Disease', 'start': 403, 'end': 412, 'mesh': 'D000783'}, {'text': 'ruptured aneurysms', 'type': 'Disease', 'start': 480, 'end': 498, 'mesh': 'D017542'}, {'text': 'cocaine abuse', 'type': 'Disease', 'start': 517, 'end': 530, 'mesh': 'D019970'}, {'text': 'subarachnoid hemorrhage', 'type': 'Disease', 'start': 610, 'end': 633, 'mesh': 'D013345'}, {'text': 'aneurysm', 'type': 'Disease', 'start': 647, 'end': 655, 'mesh': 'D000783'}, {'text': 'aneurysm', 'type': 'Disease', 'start': 673, 'end': 681, 'mesh': 'D000783'}, {'text': 'aneurysms', 'type': 'Disease', 'start': 903, 'end': 912, 'mesh': 'D000783'}, {'text': 'aneurysms', 'type': 'Disease', 'start': 977, 'end': 986, 'mesh': 'D000783'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1281, 'end': 1288, 'mesh': 'D003042'}, {'text': 'aneurysms', 'type': 'Disease', 'start': 1297, 'end': 1306, 'mesh': 'D000783'}, {'text': 'Cocaine', 'type': 'Chemical', 'start': 1320, 'end': 1327, 'mesh': 'D003042'}, {'text': 'aneurysmal rupture', 'type': 'Disease', 'start': 1344, 'end': 1362, 'mesh': 'D017542'}, {'text': 'aneurysms', 'type': 'Disease', 'start': 1414, 'end': 1423, 'mesh': 'D000783'}]"
+305,12536034,Anti-epileptic drugs-induced de novo absence seizures.,"The authors present three patients with de novo absence epilepsy after administration of carbamazepine and vigabatrin. Despite the underlying diseases, the prognosis for drug-induced de novo absence seizure is good because it subsides rapidly after discontinuing the use of the offending drugs. The gamma-aminobutyric acid-transmitted thalamocortical circuitry accounts for a major part of the underlying neurophysiology of the absence epilepsy. Because drug-induced de novo absence seizure is rare, pro-absence drugs can only be considered a promoting factor. The underlying epileptogenecity of the patients or the synergistic effects of the accompanying drugs is required to trigger the de novo absence seizure. The possibility of drug-induced aggravation should be considered whenever an unexpected increase in seizure frequency and/or new seizure types appear following a change in drug treatment. By understanding the underlying mechanism of absence epilepsy, we can avoid the inappropriate use of anticonvulsants in children with epilepsy and prevent drug-induced absence seizures.","[{'text': 'epileptic', 'type': 'Disease', 'start': 5, 'end': 14, 'mesh': 'D004827'}, {'text': 'absence seizures', 'type': 'Disease', 'start': 37, 'end': 53, 'mesh': 'D004832'}, {'text': 'absence epilepsy', 'type': 'Disease', 'start': 103, 'end': 119, 'mesh': 'D004832'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 144, 'end': 157, 'mesh': 'D002220'}, {'text': 'vigabatrin', 'type': 'Chemical', 'start': 162, 'end': 172, 'mesh': 'D020888'}, {'text': 'absence seizure', 'type': 'Disease', 'start': 246, 'end': 261, 'mesh': 'D004832'}, {'text': 'gamma-aminobutyric acid', 'type': 'Chemical', 'start': 354, 'end': 377, 'mesh': 'D005680'}, {'text': 'absence epilepsy', 'type': 'Disease', 'start': 483, 'end': 499, 'mesh': 'D004832'}, {'text': 'absence seizure', 'type': 'Disease', 'start': 530, 'end': 545, 'mesh': 'D004832'}, {'text': 'absence seizure', 'type': 'Disease', 'start': 752, 'end': 767, 'mesh': 'D004832'}, {'text': 'seizure', 'type': 'Disease', 'start': 869, 'end': 876, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 898, 'end': 905, 'mesh': 'D012640'}, {'text': 'absence epilepsy', 'type': 'Disease', 'start': 1002, 'end': 1018, 'mesh': 'D004832'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 1091, 'end': 1099, 'mesh': 'D004827'}, {'text': 'absence seizures', 'type': 'Disease', 'start': 1125, 'end': 1141, 'mesh': 'D004832'}]"
+306,7234705,Procainamide-induced polymorphous ventricular tachycardia.,"Seven cases of procainamide-induced polymorphous ventricular tachycardia are presented. In four patients, polymorphous ventricular tachycardia appeared after intravenous administration of 200 to 400 mg of procainamide for the treatment of sustained ventricular tachycardia. In the remaining three patients, procainamide was administered orally for treatment of chronic premature ventricular contractions or atrial flutter. These patients had Q-T prolongation and recurrent syncope due to polymorphous ventricular tachycardia. In four patients, the arrhythmia was rapidly diagnosed and treated with disappearance of further episodes of the arrhythmia. In two patients, the arrhythmia degenerated into irreversible ventricular fibrillation and both patients died. In the seventh patient, a permanent ventricular pacemaker was inserted and, despite continuation of procainamide therapy, polymorphous ventricular tachycardia did not reoccur. These seven cases demonstrate that procainamide can produce an acquired prolonged Q-T syndrome with polymorphous ventricular tachycardia.","[{'text': 'Procainamide', 'type': 'Chemical', 'start': 0, 'end': 12, 'mesh': 'D011342'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 34, 'end': 57, 'mesh': 'D017180'}, {'text': 'procainamide', 'type': 'Chemical', 'start': 74, 'end': 86, 'mesh': 'D011342'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 108, 'end': 131, 'mesh': 'D017180'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 178, 'end': 201, 'mesh': 'D017180'}, {'text': 'procainamide', 'type': 'Chemical', 'start': 264, 'end': 276, 'mesh': 'D011342'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 308, 'end': 331, 'mesh': 'D017180'}, {'text': 'procainamide', 'type': 'Chemical', 'start': 366, 'end': 378, 'mesh': 'D011342'}, {'text': 'premature ventricular contractions', 'type': 'Disease', 'start': 428, 'end': 462, 'mesh': 'D018879'}, {'text': 'atrial flutter', 'type': 'Disease', 'start': 466, 'end': 480, 'mesh': 'D001282'}, {'text': 'Q-T prolongation', 'type': 'Disease', 'start': 501, 'end': 517, 'mesh': 'D008133'}, {'text': 'syncope', 'type': 'Disease', 'start': 532, 'end': 539, 'mesh': 'D013575'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 560, 'end': 583, 'mesh': 'D017180'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 607, 'end': 617, 'mesh': 'D001145'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 698, 'end': 708, 'mesh': 'D001145'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 731, 'end': 741, 'mesh': 'D001145'}, {'text': 'ventricular fibrillation', 'type': 'Disease', 'start': 772, 'end': 796, 'mesh': 'D014693'}, {'text': 'procainamide', 'type': 'Chemical', 'start': 921, 'end': 933, 'mesh': 'D011342'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 956, 'end': 979, 'mesh': 'D017180'}, {'text': 'procainamide', 'type': 'Chemical', 'start': 1032, 'end': 1044, 'mesh': 'D011342'}, {'text': 'prolonged Q-T syndrome', 'type': 'Disease', 'start': 1069, 'end': 1091, 'mesh': 'D008133'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 1110, 'end': 1133, 'mesh': 'D017180'}]"
+307,8955532,Role of activation of bradykinin B2 receptors in disruption of the blood-brain barrier during acute hypertension.,"Cellular mechanisms which account for disruption the blood-brain barrier during acute hypertension are not clear. The goal of this study was to determine the role of synthesis/release of bradykinin to activate B2 receptors in disruption of the blood-brain barrier during acute hypertension. Permeability of the blood-brain barrier was quantitated by clearance of fluorescent-labeled dextran before and during phenylephrine-induced acute hypertension in rats treated with vehicle and Hoe-140 (0.1 microM). Phenylephrine infusion increased arterial pressure, arteriolar diameter and clearance of fluorescent dextran by a similar magnitude in both groups. These findings suggest that disruption of the blood-brain barrier during acute hypertension is not related to the synthesis/release of bradykinin to activate B2 receptors.","[{'text': 'bradykinin', 'type': 'Chemical', 'start': 22, 'end': 32, 'mesh': 'D001920'}, {'text': 'hypertension', 'type': 'Disease', 'start': 100, 'end': 112, 'mesh': 'D006973'}, {'text': 'hypertension', 'type': 'Disease', 'start': 200, 'end': 212, 'mesh': 'D006973'}, {'text': 'bradykinin', 'type': 'Chemical', 'start': 301, 'end': 311, 'mesh': 'D001920'}, {'text': 'hypertension', 'type': 'Disease', 'start': 391, 'end': 403, 'mesh': 'D006973'}, {'text': 'dextran', 'type': 'Chemical', 'start': 497, 'end': 504, 'mesh': 'D003911'}, {'text': 'phenylephrine', 'type': 'Chemical', 'start': 523, 'end': 536, 'mesh': 'D010656'}, {'text': 'hypertension', 'type': 'Disease', 'start': 551, 'end': 563, 'mesh': 'D006973'}, {'text': 'Hoe-140', 'type': 'Chemical', 'start': 597, 'end': 604, 'mesh': 'C065679'}, {'text': 'Phenylephrine', 'type': 'Chemical', 'start': 619, 'end': 632, 'mesh': 'D010656'}, {'text': 'dextran', 'type': 'Chemical', 'start': 720, 'end': 727, 'mesh': 'D003911'}, {'text': 'hypertension', 'type': 'Disease', 'start': 846, 'end': 858, 'mesh': 'D006973'}, {'text': 'bradykinin', 'type': 'Chemical', 'start': 902, 'end': 912, 'mesh': 'D001920'}]"
+308,2578334,5-azacytidine potentiates initiation induced by carcinogens in rat liver.,"To test the validity of the hypothesis that hypomethylation of DNA plays an important role in the initiation of carcinogenic process, 5-azacytidine (5-AzC) (10 mg/kg), an inhibitor of DNA methylation, was given to rats during the phase of repair synthesis induced by the three carcinogens, benzo[a]-pyrene (200 mg/kg), N-methyl-N-nitrosourea (60 mg/kg) and 1,2-dimethylhydrazine (1,2-DMH) (100 mg/kg). The initiated hepatocytes in the liver were assayed as the gamma-glutamyltransferase (gamma-GT) positive foci formed following a 2-week selection regimen consisting of dietary 0.02% 2-acetylaminofluorene coupled with a necrogenic dose of CCl4. The results obtained indicate that with all three carcinogens, administration of 5-AzC during repair synthesis increased the incidence of initiated hepatocytes, for example 10-20 foci/cm2 in 5-AzC and carcinogen-treated rats compared with 3-5 foci/cm2 in rats treated with carcinogen only. Administration of [3H]-5-azadeoxycytidine during the repair synthesis induced by 1,2-DMH further showed that 0.019 mol % of cytosine residues in DNA were substituted by the analogue, indicating that incorporation of 5-AzC occurs during repair synthesis. In the absence of the carcinogen, 5-AzC given after a two thirds partial hepatectomy, when its incorporation should be maximum, failed to induce any gamma-GT positive foci. The results suggest that hypomethylation of DNA per se may not be sufficient for initiation. Perhaps two events might be necessary for initiation, the first caused by the carcinogen and a second involving hypomethylation of DNA.","[{'text': '5-azacytidine', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'D001374'}, {'text': 'initiation induced by carcinogens', 'type': 'Disease', 'start': 26, 'end': 59, 'mesh': 'D011230'}, {'text': 'initiation of carcinogenic process', 'type': 'Disease', 'start': 172, 'end': 206, 'mesh': 'D011230'}, {'text': '5-azacytidine', 'type': 'Chemical', 'start': 208, 'end': 221, 'mesh': 'D001374'}, {'text': '5-AzC', 'type': 'Chemical', 'start': 223, 'end': 228, 'mesh': 'D001374'}, {'text': 'benzo[a]-pyrene', 'type': 'Chemical', 'start': 364, 'end': 379, 'mesh': 'D001564'}, {'text': 'N-methyl-N-nitrosourea', 'type': 'Chemical', 'start': 393, 'end': 415, 'mesh': 'D008770'}, {'text': '1,2-dimethylhydrazine', 'type': 'Chemical', 'start': 431, 'end': 452, 'mesh': 'D019813'}, {'text': '1,2-DMH', 'type': 'Chemical', 'start': 454, 'end': 461, 'mesh': 'D019813'}, {'text': '2-acetylaminofluorene', 'type': 'Chemical', 'start': 658, 'end': 679, 'mesh': 'D015073'}, {'text': 'CCl4', 'type': 'Chemical', 'start': 714, 'end': 718, 'mesh': 'D002251'}, {'text': '5-AzC', 'type': 'Chemical', 'start': 801, 'end': 806, 'mesh': 'D001374'}, {'text': '5-AzC', 'type': 'Chemical', 'start': 911, 'end': 916, 'mesh': 'D001374'}, {'text': '[3H]-5-azadeoxycytidine', 'type': 'Chemical', 'start': 1028, 'end': 1051, 'mesh': 'C014347'}, {'text': '1,2-DMH', 'type': 'Chemical', 'start': 1091, 'end': 1098, 'mesh': 'D019813'}, {'text': 'cytosine', 'type': 'Chemical', 'start': 1134, 'end': 1142, 'mesh': 'D003596'}, {'text': '5-AzC', 'type': 'Chemical', 'start': 1226, 'end': 1231, 'mesh': 'D001374'}, {'text': '5-AzC', 'type': 'Chemical', 'start': 1298, 'end': 1303, 'mesh': 'D001374'}]"
+309,11532387,Withdrawal-emergent rabbit syndrome during dose reduction of risperidone.,"Rabbit syndrome (RS) is a rare extrapyramidal side effect caused by prolonged neuroleptic medication. Here we present a case of withdrawal-emergent RS, which is the first of its kind to be reported. The patient developed RS during dose reduction of risperidone. The symptom was treated successfully with trihexyphenidyl anticholinergic therapy. The underlying mechanism of withdrawal-emergent RS in the present case may have been related to the pharmacological profile of risperidone, a serotonin-dopamine antagonist, suggesting the pathophysiologic influence of the serotonin system in the development of RS.","[{'text': 'risperidone', 'type': 'Chemical', 'start': 61, 'end': 72, 'mesh': 'D018967'}, {'text': 'Rabbit syndrome', 'type': 'Disease', 'start': 74, 'end': 89, 'mesh': 'D001480'}, {'text': 'RS', 'type': 'Disease', 'start': 91, 'end': 93, 'mesh': 'D001480'}, {'text': 'RS', 'type': 'Disease', 'start': 295, 'end': 297, 'mesh': 'D001480'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 323, 'end': 334, 'mesh': 'D018967'}, {'text': 'trihexyphenidyl', 'type': 'Chemical', 'start': 378, 'end': 393, 'mesh': 'D014282'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 546, 'end': 557, 'mesh': 'D018967'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 561, 'end': 570, 'mesh': 'D012701'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 571, 'end': 579, 'mesh': 'D004298'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 641, 'end': 650, 'mesh': 'D012701'}, {'text': 'RS', 'type': 'Disease', 'start': 680, 'end': 682, 'mesh': 'D001480'}]"
+310,3173179,Verapamil withdrawal as a possible cause of myocardial infarction in a hypertensive woman with a normal coronary angiogram.,"Verapamil is an effective and relatively-safe antihypertensive drug. Serious adverse effects are uncommon and mainly have been related to the depression of cardiac contractility and conduction, especially when the drug is combined with beta-blocking agents. We report a case in which myocardial infarction coincided with the introduction of captopril and the withdrawal of verapamil in a previously asymptomatic woman with severe hypertension. Possible mechanisms that involve a verapamil-related increase in platelet and/or vascular alpha 2-adrenoreceptor affinity for catecholamines are discussed.","[{'text': 'Verapamil', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D014700'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 44, 'end': 65, 'mesh': 'D009203'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 71, 'end': 83, 'mesh': 'D006973'}, {'text': 'Verapamil', 'type': 'Chemical', 'start': 124, 'end': 133, 'mesh': 'D014700'}, {'text': 'depression', 'type': 'Disease', 'start': 266, 'end': 276, 'mesh': 'D003866'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 408, 'end': 429, 'mesh': 'D009203'}, {'text': 'captopril', 'type': 'Chemical', 'start': 465, 'end': 474, 'mesh': 'D002216'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 497, 'end': 506, 'mesh': 'D014700'}, {'text': 'hypertension', 'type': 'Disease', 'start': 554, 'end': 566, 'mesh': 'D006973'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 603, 'end': 612, 'mesh': 'D014700'}, {'text': 'catecholamines', 'type': 'Chemical', 'start': 694, 'end': 708, 'mesh': 'D002395'}]"
+311,3856631,Remission induction of meningeal leukemia with high-dose intravenous methotrexate.,"Twenty children with acute lymphoblastic leukemia who developed meningeal disease were treated with a high-dose intravenous methotrexate regimen that was designed to achieve and maintain CSF methotrexate concentrations of 10(-5) mol/L without the need for concomitant intrathecal dosing. The methotrexate was administered as a loading dose of 6,000 mg/m2 for a period of one hour followed by an infusion of 1,200 mg/m2/h for 23 hours. Leucovorin rescue was initiated 12 hours after the end of the infusion with a loading dose of 200 mg/m2 followed by 12 mg/m2 every three hours for six doses and then every six hours until the plasma methotrexate level decreased to less than 1 X 10(-7) mol/L. The mean steady-state plasma and CSF methotrexate concentrations achieved were 1.1 X 10(-3) mol/L and 3.6 X 10(-5) mol/L, respectively. All 20 patients responded to this regimen, 16/20 (80%) achieved a complete remission, and 20% obtained a partial remission. The most common toxicities encountered were transient serum transaminase and bilirubin elevations, neutropenia, and mucositis. One patient had focal seizures and transient hemiparesis but recovered completely. High-dose intravenous methotrexate is an effective treatment for the induction of remission after meningeal relapse in acute lymphoblastic leukemia.","[{'text': 'meningeal leukemia', 'type': 'Disease', 'start': 23, 'end': 41, 'mesh': 'D008577'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 69, 'end': 81, 'mesh': 'D008727'}, {'text': 'acute lymphoblastic leukemia', 'type': 'Disease', 'start': 104, 'end': 132, 'mesh': 'D054198'}, {'text': 'meningeal disease', 'type': 'Disease', 'start': 147, 'end': 164, 'mesh': 'D002493'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 207, 'end': 219, 'mesh': 'D008727'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 274, 'end': 286, 'mesh': 'D008727'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 375, 'end': 387, 'mesh': 'D008727'}, {'text': 'Leucovorin', 'type': 'Chemical', 'start': 518, 'end': 528, 'mesh': 'D002955'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 717, 'end': 729, 'mesh': 'D008727'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 814, 'end': 826, 'mesh': 'D008727'}, {'text': 'toxicities', 'type': 'Disease', 'start': 1053, 'end': 1063, 'mesh': 'D064420'}, {'text': 'bilirubin', 'type': 'Chemical', 'start': 1114, 'end': 1123, 'mesh': 'D001663'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 1136, 'end': 1147, 'mesh': 'D009503'}, {'text': 'mucositis', 'type': 'Disease', 'start': 1153, 'end': 1162, 'mesh': 'D052016'}, {'text': 'seizures', 'type': 'Disease', 'start': 1186, 'end': 1194, 'mesh': 'D012640'}, {'text': 'transient hemiparesis', 'type': 'Disease', 'start': 1199, 'end': 1220, 'mesh': 'D010291'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 1269, 'end': 1281, 'mesh': 'D008727'}, {'text': 'acute lymphoblastic leukemia', 'type': 'Disease', 'start': 1366, 'end': 1394, 'mesh': 'D054198'}]"
+312,2522601,"Hypersensitivity to carbamazepine presenting with a leukemoid reaction, eosinophilia, erythroderma, and renal failure.","We report a patient in whom hypersensitivity to carbamazepine presented with generalized erythroderma, a severe leukemoid reaction, eosinophilia, hyponatremia, and renal failure. This is the first report of such an unusual reaction to carbamazepine.","[{'text': 'Hypersensitivity', 'type': 'Disease', 'start': 0, 'end': 16, 'mesh': 'D004342'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 20, 'end': 33, 'mesh': 'D002220'}, {'text': 'leukemoid reaction', 'type': 'Disease', 'start': 52, 'end': 70, 'mesh': 'D007955'}, {'text': 'eosinophilia', 'type': 'Disease', 'start': 72, 'end': 84, 'mesh': 'D004802'}, {'text': 'erythroderma', 'type': 'Disease', 'start': 86, 'end': 98, 'mesh': 'D003873'}, {'text': 'renal failure', 'type': 'Disease', 'start': 104, 'end': 117, 'mesh': 'D051437'}, {'text': 'hypersensitivity', 'type': 'Disease', 'start': 147, 'end': 163, 'mesh': 'D004342'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 167, 'end': 180, 'mesh': 'D002220'}, {'text': 'erythroderma', 'type': 'Disease', 'start': 208, 'end': 220, 'mesh': 'D003873'}, {'text': 'leukemoid reaction', 'type': 'Disease', 'start': 231, 'end': 249, 'mesh': 'D007955'}, {'text': 'eosinophilia', 'type': 'Disease', 'start': 251, 'end': 263, 'mesh': 'D004802'}, {'text': 'hyponatremia', 'type': 'Disease', 'start': 265, 'end': 277, 'mesh': 'D007010'}, {'text': 'renal failure', 'type': 'Disease', 'start': 283, 'end': 296, 'mesh': 'D051437'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 354, 'end': 367, 'mesh': 'D002220'}]"
+313,8741744,The interpeduncular nucleus regulates nicotine's effects on free-field activity.,"Partial lesions were made with kainic acid in the interpeduncular nucleus of the ventral midbrain of the rat. Compared with sham-operated controls, lesions significantly (p < 0.25) blunted the early (<60 min) free-field locomotor hypoactivity caused by nicotine (0.5 mg kg(-1), i.m.), enhanced the later (60-120 min) nicotine-induced hyperactivity, and raised spontaneous nocturnal activity. Lesions reduced the extent of immunohistological staining for choline acetyltransferase in the interpeduncular nucleus (p <0.025), but not for tyrosine hydroxylase in the surrounding catecholaminergic A10 region. We conclude that the interpeduncular nucleus mediates nicotinic depression of locomotor activity and dampens nicotinic arousal mechanisms located elsewhere in the brain.","[{'text': 'nicotine', 'type': 'Chemical', 'start': 38, 'end': 46, 'mesh': 'D009538'}, {'text': 'kainic acid', 'type': 'Chemical', 'start': 112, 'end': 123, 'mesh': 'D007608'}, {'text': 'locomotor hypoactivity', 'type': 'Disease', 'start': 301, 'end': 323, 'mesh': 'D009069'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 334, 'end': 342, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 398, 'end': 406, 'mesh': 'D009538'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 415, 'end': 428, 'mesh': 'D006948'}, {'text': 'choline', 'type': 'Chemical', 'start': 535, 'end': 542, 'mesh': 'D002794'}, {'text': 'tyrosine', 'type': 'Chemical', 'start': 616, 'end': 624, 'mesh': 'D014443'}, {'text': 'depression', 'type': 'Disease', 'start': 750, 'end': 760, 'mesh': 'D003866'}]"
+314,17491223,Assessment of a new non-invasive index of cardiac performance for detection of dobutamine-induced myocardial ischemia.,"BACKGROUND: Electrocardiography has a very low sensitivity in detecting dobutamine-induced myocardial ischemia. OBJECTIVES: To assess the added diagnostic value of a new cardiac performance index (dP/dtejc) measurement, based on brachial artery flow changes, as compared to standard 12-lead ECG, for detecting dobutamine-induced myocardial ischemia, using Tc99m-Sestamibi single-photon emission computed tomography as the gold standard of comparison to assess the presence or absence of ischemia. METHODS: The study group comprised 40 patients undergoing Sestamibi-SPECT/dobutamine stress test. Simultaneous measurements of ECG and brachial artery dP/dtejc were performed at each dobutamine level. In 19 of the 40 patients perfusion defects compatible with ischemia were detected on SPECT. The increase in dP/dtejc during infusion of dobutamine in this group was severely impaired as compared to the non-ischemic group. dP/dtejc outcome was combined with the ECG results, giving an ECG-enhanced value, and compared to ECG alone. RESULTS: The sensitivity improved dramatically from 16% to 79%, positive predictive value increased from 60% to 68% and negative predictive value from 54% to 78%, and specificity decreased from 90% to 67%. CONCLUSIONS: If ECG alone is used for specificity, the combination with dP/dtejc improved the sensitivity of the test and could be a cost-savings alternative to cardiac imaging or perfusion studies to detect myocardial ischemia, especially in patients unable to exercise.","[{'text': 'dobutamine', 'type': 'Chemical', 'start': 79, 'end': 89, 'mesh': 'D004280'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 98, 'end': 117, 'mesh': 'D017202'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 191, 'end': 201, 'mesh': 'D004280'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 210, 'end': 229, 'mesh': 'D017202'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 429, 'end': 439, 'mesh': 'D004280'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 448, 'end': 467, 'mesh': 'D017202'}, {'text': 'Tc99m-Sestamibi', 'type': 'Chemical', 'start': 475, 'end': 490, 'mesh': 'D017256'}, {'text': 'ischemia', 'type': 'Disease', 'start': 606, 'end': 614, 'mesh': 'D007511'}, {'text': 'Sestamibi', 'type': 'Chemical', 'start': 674, 'end': 683, 'mesh': 'D017256'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 690, 'end': 700, 'mesh': 'D004280'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 799, 'end': 809, 'mesh': 'D004280'}, {'text': 'ischemia', 'type': 'Disease', 'start': 876, 'end': 884, 'mesh': 'D007511'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 953, 'end': 963, 'mesh': 'D004280'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 1562, 'end': 1581, 'mesh': 'D017202'}]"
+315,18004067,Acute liver failure in two patients with regular alcohol consumption ingesting paracetamol at therapeutic dosage.,"BACKGROUND: The possible role of alcohol in the development of hepatotoxicity associated with therapeutic doses of paracetamol (acetaminophen) is currently debated. CASE REPORT: We describe 2 patients who were regular consumers of alcohol and who developed liver failure within 3-5 days after hospitalization and stopping alcohol consumption while being treated with 4 g paracetamol/day. A paracetamol serum level obtained in one of these patients was not in the toxic range. Possible risk factors for the development of hepatotoxicity in patients treated with therapeutic doses of paracetamol are discussed. CONCLUSION: In patients with risk factors, e.g. regular consumption of alcohol, liver failure is possible when therapeutic doses are ingested. We propose that the paracetamol dose should not exceed 2 g/day in such patients and that their liver function should be monitored closely while being treated with paracetamol.","[{'text': 'Acute liver failure', 'type': 'Disease', 'start': 0, 'end': 19, 'mesh': 'D017114'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 49, 'end': 56, 'mesh': 'D000431'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 79, 'end': 90, 'mesh': 'D000082'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 147, 'end': 154, 'mesh': 'D000431'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 177, 'end': 191, 'mesh': 'D056486'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 229, 'end': 240, 'mesh': 'D000082'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 242, 'end': 255, 'mesh': 'D000082'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 345, 'end': 352, 'mesh': 'D000431'}, {'text': 'liver failure', 'type': 'Disease', 'start': 371, 'end': 384, 'mesh': 'D017093'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 436, 'end': 443, 'mesh': 'D000431'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 485, 'end': 496, 'mesh': 'D000082'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 504, 'end': 515, 'mesh': 'D000082'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 635, 'end': 649, 'mesh': 'D056486'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 696, 'end': 707, 'mesh': 'D000082'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 794, 'end': 801, 'mesh': 'D000431'}, {'text': 'liver failure', 'type': 'Disease', 'start': 803, 'end': 816, 'mesh': 'D017093'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 886, 'end': 897, 'mesh': 'D000082'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 1029, 'end': 1040, 'mesh': 'D000082'}]"
+316,12443032,Cocaine related chest pain: are we seeing the tip of an iceberg?,"The recreational use of cocaine is on the increase. The emergency nurse ought to be familiar with some of the cardiovascular consequences of cocaine use. In particular, the tendency of cocaine to produce chest pain ought to be in the mind of the emergency nurse when faced with a young victim of chest pain who is otherwise at low risk. The mechanism of chest pain related to cocaine use is discussed and treatment dilemmas are discussed. Finally, moral issues relating to the testing of potential cocaine users will be addressed.","[{'text': 'Cocaine', 'type': 'Chemical', 'start': 0, 'end': 7, 'mesh': 'D003042'}, {'text': 'chest pain', 'type': 'Disease', 'start': 16, 'end': 26, 'mesh': 'D002637'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 89, 'end': 96, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 206, 'end': 213, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 250, 'end': 257, 'mesh': 'D003042'}, {'text': 'chest pain', 'type': 'Disease', 'start': 269, 'end': 279, 'mesh': 'D002637'}, {'text': 'chest pain', 'type': 'Disease', 'start': 361, 'end': 371, 'mesh': 'D002637'}, {'text': 'chest pain', 'type': 'Disease', 'start': 419, 'end': 429, 'mesh': 'D002637'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 441, 'end': 448, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 563, 'end': 570, 'mesh': 'D003042'}]"
+317,17615423,"Severe rhabdomyolysis and acute renal failure secondary to concomitant use of simvastatin, amiodarone, and atazanavir.","OBJECTIVE: To report a case of a severe interaction between simvastatin, amiodarone, and atazanavir resulting in rhabdomyolysis and acute renal failure. BACKGROUND: A 72-year-old white man with underlying human immunodeficiency virus, atrial fibrillation, coronary artery disease, and hyperlipidemia presented with generalized pain, fatigue, and dark orange urine for 3 days. The patient was taking 80 mg simvastatin at bedtime (initiated 27 days earlier); amiodarone at a dose of 400 mg daily for 7 days, then 200 mg daily (initiated 19 days earlier); and 400 mg atazanavir daily (initiated at least 2 years previously). Laboratory evaluation revealed 66,680 U/L creatine kinase, 93 mg/dL blood urea nitrogen, 4.6 mg/dL creatinine, 1579 U/L aspartate aminotransferase, and 738 U/L alanine aminotransferase. Simvastatin, amiodarone, and the patient's human immunodeficiency virus medications were all temporarily discontinued and the patient was given forced alkaline diuresis and started on dialysis. Nine days later the patient's creatine kinase had dropped to 1695 U/L and creatinine was 3.3 mg/dL. The patient was discharged and continued outpatient dialysis for 1 month until his renal function recovered. DISCUSSION: The risk of rhabdomyolysis is increased in the presence of concomitant drugs that inhibit simvastatin metabolism. Simvastatin is metabolized by CYP3A4. Amiodarone and atazanavir are recognized CYP3A4 inhibitors. CONCLUSIONS: Pharmacokinetic differences in statins are an important consideration for assessing the risk of potential drug interactions. In patients requiring the concurrent use of statins and CYP3A4 inhibitors, pravastatin, fluvastatin, and rosuvastatin carry the lowest risk of drug interactions; atorvastatin carries moderate risk, whereas simvastatin and lovastatin have the highest risk and should be avoided in patients taking concomitant CYP3A4 inhibitors.","[{'text': 'rhabdomyolysis', 'type': 'Disease', 'start': 7, 'end': 21, 'mesh': 'D012206'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 26, 'end': 45, 'mesh': 'D058186'}, {'text': 'simvastatin', 'type': 'Chemical', 'start': 78, 'end': 89, 'mesh': 'D019821'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 91, 'end': 101, 'mesh': 'D000638'}, {'text': 'atazanavir', 'type': 'Chemical', 'start': 107, 'end': 117, 'mesh': 'C413408'}, {'text': 'simvastatin', 'type': 'Chemical', 'start': 179, 'end': 190, 'mesh': 'D019821'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 192, 'end': 202, 'mesh': 'D000638'}, {'text': 'atazanavir', 'type': 'Chemical', 'start': 208, 'end': 218, 'mesh': 'C413408'}, {'text': 'rhabdomyolysis', 'type': 'Disease', 'start': 232, 'end': 246, 'mesh': 'D012206'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 251, 'end': 270, 'mesh': 'D058186'}, {'text': 'human immunodeficiency virus', 'type': 'Disease', 'start': 324, 'end': 352, 'mesh': 'D015658'}, {'text': 'atrial fibrillation', 'type': 'Disease', 'start': 354, 'end': 373, 'mesh': 'D001281'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 375, 'end': 398, 'mesh': 'D003324'}, {'text': 'hyperlipidemia', 'type': 'Disease', 'start': 404, 'end': 418, 'mesh': 'D006949'}, {'text': 'pain', 'type': 'Disease', 'start': 446, 'end': 450, 'mesh': 'D010146'}, {'text': 'fatigue', 'type': 'Disease', 'start': 452, 'end': 459, 'mesh': 'D005221'}, {'text': 'simvastatin', 'type': 'Chemical', 'start': 524, 'end': 535, 'mesh': 'D019821'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 576, 'end': 586, 'mesh': 'D000638'}, {'text': 'atazanavir', 'type': 'Chemical', 'start': 683, 'end': 693, 'mesh': 'C413408'}, {'text': 'creatine', 'type': 'Chemical', 'start': 783, 'end': 791, 'mesh': 'D003401'}, {'text': 'blood urea nitrogen', 'type': 'Chemical', 'start': 809, 'end': 828, 'mesh': 'D001806'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 840, 'end': 850, 'mesh': 'D003404'}, {'text': 'aspartate', 'type': 'Chemical', 'start': 861, 'end': 870, 'mesh': 'D001224'}, {'text': 'alanine', 'type': 'Chemical', 'start': 901, 'end': 908, 'mesh': 'D000409'}, {'text': 'Simvastatin', 'type': 'Chemical', 'start': 927, 'end': 938, 'mesh': 'D019821'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 940, 'end': 950, 'mesh': 'D000638'}, {'text': 'human immunodeficiency virus', 'type': 'Disease', 'start': 970, 'end': 998, 'mesh': 'D015658'}, {'text': 'creatine', 'type': 'Chemical', 'start': 1151, 'end': 1159, 'mesh': 'D003401'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1195, 'end': 1205, 'mesh': 'D003404'}, {'text': 'rhabdomyolysis', 'type': 'Disease', 'start': 1354, 'end': 1368, 'mesh': 'D012206'}, {'text': 'simvastatin', 'type': 'Chemical', 'start': 1432, 'end': 1443, 'mesh': 'D019821'}, {'text': 'Simvastatin', 'type': 'Chemical', 'start': 1456, 'end': 1467, 'mesh': 'D019821'}, {'text': 'Amiodarone', 'type': 'Chemical', 'start': 1494, 'end': 1504, 'mesh': 'D000638'}, {'text': 'atazanavir', 'type': 'Chemical', 'start': 1509, 'end': 1519, 'mesh': 'C413408'}, {'text': 'statins', 'type': 'Chemical', 'start': 1598, 'end': 1605, 'mesh': 'D019821'}, {'text': 'statins', 'type': 'Chemical', 'start': 1736, 'end': 1743, 'mesh': 'D019821'}, {'text': 'pravastatin', 'type': 'Chemical', 'start': 1767, 'end': 1778, 'mesh': 'D017035'}, {'text': 'fluvastatin', 'type': 'Chemical', 'start': 1780, 'end': 1791, 'mesh': 'C065180'}, {'text': 'rosuvastatin', 'type': 'Chemical', 'start': 1797, 'end': 1809, 'mesh': 'C422923'}, {'text': 'atorvastatin', 'type': 'Chemical', 'start': 1854, 'end': 1866, 'mesh': 'C065179'}, {'text': 'simvastatin', 'type': 'Chemical', 'start': 1898, 'end': 1909, 'mesh': 'D019821'}, {'text': 'lovastatin', 'type': 'Chemical', 'start': 1914, 'end': 1924, 'mesh': 'D008148'}]"
+318,8558192,Phase II trial of vinorelbine in metastatic squamous cell esophageal carcinoma. European Organization for Research and Treatment of Cancer Gastrointestinal Treat Cancer Cooperative Group.,"PURPOSE: To evaluate the response rate and toxic effects of vinorelbine (VNB) administered as a single agent in metastatic squamous cell esophageal carcinoma. PATIENTS AND METHODS: Forty-six eligible patients with measurable lesions were included and were stratified according to previous chemotherapy. Thirty patients without prior chemotherapy and 16 pretreated with cisplatin-based chemotherapy were assessable for toxicity and response. VNB was administered weekly as a 25-mg/m2 short intravenous (i.v.) infusion. RESULTS: Six of 30 patients (20%) without prior chemotherapy achieved a partial response (PR) (95% confidence interval [CI], 8% to 39%). The median duration of response was 21 weeks (range, 17 to 28). One of 16 patients (6%) with prior chemotherapy had a complete response (CR) of 31 weeks' duration (95% CI, 0% to 30%). The overall response rate (World Health Organization [WHO] criteria) was 15% (CR, 2%; PR 13%; 95% CI, 6% to 29%). The median dose-intensity (DI) was 20 mg/m2/wk. VNB was well tolerated and zero instances of WHO grade 4 nonhematologic toxicity occurred. At least one episode of grade 3 or 4 granulocytopenia was seen in 59% of patients. A grade 2 or 3 infection occurred in 16% of patients, but no toxic deaths occurred. Other side effects were rare, and peripheral neurotoxicity has been minor (26% grade 1). CONCLUSION: These data indicate that VNB is an active agent in metastatic esophageal squamous cell carcinoma. Given its excellent tolerance profile and low toxicity, further evaluation of VNB in combination therapy is warranted.","[{'text': 'vinorelbine', 'type': 'Chemical', 'start': 18, 'end': 29, 'mesh': 'C030852'}, {'text': 'squamous cell esophageal carcinoma', 'type': 'Disease', 'start': 44, 'end': 78, 'mesh': 'C562729'}, {'text': 'Cancer', 'type': 'Disease', 'start': 132, 'end': 138, 'mesh': 'D009369'}, {'text': 'Cancer', 'type': 'Disease', 'start': 162, 'end': 168, 'mesh': 'D009369'}, {'text': 'vinorelbine', 'type': 'Chemical', 'start': 248, 'end': 259, 'mesh': 'C030852'}, {'text': 'VNB', 'type': 'Chemical', 'start': 261, 'end': 264, 'mesh': 'C030852'}, {'text': 'squamous cell esophageal carcinoma', 'type': 'Disease', 'start': 311, 'end': 345, 'mesh': 'C562729'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 557, 'end': 566, 'mesh': 'D002945'}, {'text': 'toxicity', 'type': 'Disease', 'start': 606, 'end': 614, 'mesh': 'D064420'}, {'text': 'VNB', 'type': 'Chemical', 'start': 629, 'end': 632, 'mesh': 'C030852'}, {'text': 'VNB', 'type': 'Chemical', 'start': 1189, 'end': 1192, 'mesh': 'C030852'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1261, 'end': 1269, 'mesh': 'D064420'}, {'text': 'granulocytopenia', 'type': 'Disease', 'start': 1317, 'end': 1333, 'mesh': 'D000380'}, {'text': 'infection', 'type': 'Disease', 'start': 1378, 'end': 1387, 'mesh': 'D007239'}, {'text': 'deaths', 'type': 'Disease', 'start': 1430, 'end': 1436, 'mesh': 'D003643'}, {'text': 'peripheral neurotoxicity', 'type': 'Disease', 'start': 1481, 'end': 1505, 'mesh': 'D010523'}, {'text': 'VNB', 'type': 'Chemical', 'start': 1573, 'end': 1576, 'mesh': 'C030852'}, {'text': 'esophageal squamous cell carcinoma', 'type': 'Disease', 'start': 1610, 'end': 1644, 'mesh': 'C562729'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1692, 'end': 1700, 'mesh': 'D064420'}, {'text': 'VNB', 'type': 'Chemical', 'start': 1724, 'end': 1727, 'mesh': 'C030852'}]"
+319,11135224,"Paclitaxel, cisplatin, and gemcitabine combination chemotherapy within a multidisciplinary therapeutic approach in metastatic nonsmall cell lung carcinoma.","BACKGROUND: Cisplatin-based chemotherapy combinations improve quality of life and survival in advanced nonsmall cell lung carcinoma (NSCLC). The emergence of new active drugs might translate into more effective regimens for the treatment of this disease. METHODS: The objective of this study was to determine the feasibility, response rate, and toxicity of a paclitaxel, cisplatin, and gemcitabine combination to treat metastatic NSCLC. Thirty-five consecutive chemotherapy-naive patients with Stage IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0-2 were treated with a combination of paclitaxel (135 mg/m(2) given intravenously in 3 hours) on Day 1, cisplatin (120 mg/m(2) given intravenously in 6 hours) on Day 1, and gemcitabine (800 mg/m(2) given intravenously in 30 minutes) on Days 1 and 8, every 4 weeks. Although responding patients were scheduled to receive consolidation radiotherapy and 24 patients received preplanned second-line chemotherapy after disease progression, the response and toxicity rates reported refer only to the chemotherapy regimen given. RESULTS: All the patients were examined for toxicity; 34 were examinable for response. An objective response was observed in 73.5% of the patients (95% confidence interval [CI], 55.6-87.1%), including 4 complete responses (11.7%). According to intention-to-treat, the overall response rate was 71.4% (95% CI, 53. 7-85.4%). After 154 courses of therapy, the median dose intensity was 131 mg/m(2) for paclitaxel (97.3%), 117 mg/m(2) for cisplatin (97.3%), and 1378 mg/m(2) for gemcitabine (86.2%). World Health Organization Grade 3-4 neutropenia and thrombocytopenia occurred in 39.9% and 11.4% of patients, respectively. There was one treatment-related death. Nonhematologic toxicities were mild. After a median follow-up of 22 months, the median progression free survival rate was 7 months, and the median survival time was 16 months. CONCLUSIONS: The combination of paclitaxel, cisplatin, and gemcitabine is well tolerated and shows high activity in metastatic NSCLC. This treatment merits further comparison with other cisplatin-based regimens.","[{'text': 'Paclitaxel', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D017239'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 12, 'end': 21, 'mesh': 'D002945'}, {'text': 'gemcitabine', 'type': 'Chemical', 'start': 27, 'end': 38, 'mesh': 'C056507'}, {'text': 'nonsmall cell lung carcinoma', 'type': 'Disease', 'start': 126, 'end': 154, 'mesh': 'D002289'}, {'text': 'Cisplatin', 'type': 'Chemical', 'start': 168, 'end': 177, 'mesh': 'D002945'}, {'text': 'nonsmall cell lung carcinoma', 'type': 'Disease', 'start': 259, 'end': 287, 'mesh': 'D002289'}, {'text': 'NSCLC', 'type': 'Disease', 'start': 289, 'end': 294, 'mesh': 'D002289'}, {'text': 'toxicity', 'type': 'Disease', 'start': 501, 'end': 509, 'mesh': 'D064420'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 515, 'end': 525, 'mesh': 'D017239'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 527, 'end': 536, 'mesh': 'D002945'}, {'text': 'gemcitabine', 'type': 'Chemical', 'start': 542, 'end': 553, 'mesh': 'C056507'}, {'text': 'NSCLC', 'type': 'Disease', 'start': 586, 'end': 591, 'mesh': 'D002289'}, {'text': 'NSCLC', 'type': 'Disease', 'start': 659, 'end': 664, 'mesh': 'D002289'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 768, 'end': 778, 'mesh': 'D017239'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 834, 'end': 843, 'mesh': 'D002945'}, {'text': 'gemcitabine', 'type': 'Chemical', 'start': 903, 'end': 914, 'mesh': 'C056507'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1182, 'end': 1190, 'mesh': 'D064420'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1296, 'end': 1304, 'mesh': 'D064420'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 1651, 'end': 1661, 'mesh': 'D017239'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 1687, 'end': 1696, 'mesh': 'D002945'}, {'text': 'gemcitabine', 'type': 'Chemical', 'start': 1727, 'end': 1738, 'mesh': 'C056507'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 1784, 'end': 1795, 'mesh': 'D009503'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 1800, 'end': 1816, 'mesh': 'D013921'}, {'text': 'death', 'type': 'Disease', 'start': 1904, 'end': 1909, 'mesh': 'D003643'}, {'text': 'toxicities', 'type': 'Disease', 'start': 1926, 'end': 1936, 'mesh': 'D064420'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 2119, 'end': 2129, 'mesh': 'D017239'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 2131, 'end': 2140, 'mesh': 'D002945'}, {'text': 'gemcitabine', 'type': 'Chemical', 'start': 2146, 'end': 2157, 'mesh': 'C056507'}, {'text': 'NSCLC', 'type': 'Disease', 'start': 2214, 'end': 2219, 'mesh': 'D002289'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 2273, 'end': 2282, 'mesh': 'D002945'}]"
+320,8590259,Evaluation of adverse reactions of aponidine hydrochloride ophthalmic solution.,"We prospectively evaluated the adverse reactions of apraclonidine in 20 normal volunteers by instilling a single drop of 1% apraclonidine in their right eyes. Examinations, including blood pressure, pulse rate, conjunctiva and cornea, intraocular pressure (IOP), pupil diameter, basal tear secretion and margin reflex distance of both upper and lower eyelids, were performed prior to entry and at 1, 3, 5 and 7 hours after instillation. The ocular hypotensive effects were statistically significant for apraclonidine-treated eyes throughout the study and also statistically significant for contralateral eyes from three hours after topical administration of 1% apraclonidine. Decreases in systolic blood pressure were statistically, but not clinically, significant. No significant changes in diastolic blood pressure, pulse rate and basal tear secretion were noted. Conjunctival blanching and mydriasis were commonly found. Upper lid retraction was frequently noted. While the elevations of the upper lid margin in most subjects were not more than 2 mm and did not cause noticeable change in appearance, one subject suffered from mechanical entropion and marked corneal abrasion 3 hours after instillation of the medication. This may well be a particularly notable finding in Asian people.","[{'text': 'aponidine hydrochloride', 'type': 'Chemical', 'start': 35, 'end': 58, 'mesh': 'C016986'}, {'text': 'apraclonidine', 'type': 'Chemical', 'start': 132, 'end': 145, 'mesh': 'C016986'}, {'text': 'apraclonidine', 'type': 'Chemical', 'start': 204, 'end': 217, 'mesh': 'C016986'}, {'text': 'ocular hypotensive', 'type': 'Disease', 'start': 521, 'end': 539, 'mesh': 'D015814'}, {'text': 'apraclonidine', 'type': 'Chemical', 'start': 583, 'end': 596, 'mesh': 'C016986'}, {'text': 'apraclonidine', 'type': 'Chemical', 'start': 741, 'end': 754, 'mesh': 'C016986'}, {'text': 'Decreases in systolic blood pressure', 'type': 'Disease', 'start': 756, 'end': 792, 'mesh': 'D007022'}, {'text': 'Conjunctival blanching', 'type': 'Disease', 'start': 946, 'end': 968, 'mesh': 'D003229'}, {'text': 'mydriasis', 'type': 'Disease', 'start': 973, 'end': 982, 'mesh': 'D015878'}, {'text': 'entropion', 'type': 'Disease', 'start': 1221, 'end': 1230, 'mesh': 'D004774'}, {'text': 'corneal abrasion', 'type': 'Disease', 'start': 1242, 'end': 1258, 'mesh': 'D003316'}]"
+321,2096243,Carmofur-induced organic mental disorders.,"Organic mental disorder was observed in a 29-year-old female in the prognostic period after the onset of carmofur-induced leukoencephalopathy. Symptoms such as euphoria, emotional lability and puerile attitude noted in the patient were diagnosed as organic personality syndrome according to the criteria defined in the DSM-III-R. It is referred to as a frontal lobe syndrome. Brain CT revealed a periventricular low density area in the frontal white matter and moderate dilatation of the lateral ventricles especially at the bilateral anterior horns. Consequently, carmofur-induced leukoencephalopathy may uncommonly result in organic personality syndrome in the residual state. It may be attributed to the structural damage to the frontal lobe.","[{'text': 'Carmofur', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'C017367'}, {'text': 'organic mental disorders', 'type': 'Disease', 'start': 17, 'end': 41, 'mesh': 'D019965'}, {'text': 'Organic mental disorder', 'type': 'Disease', 'start': 43, 'end': 66, 'mesh': 'D019965'}, {'text': 'carmofur', 'type': 'Chemical', 'start': 148, 'end': 156, 'mesh': 'C017367'}, {'text': 'leukoencephalopathy', 'type': 'Disease', 'start': 165, 'end': 184, 'mesh': 'D056784'}, {'text': 'organic personality syndrome', 'type': 'Disease', 'start': 292, 'end': 320, 'mesh': 'D010554'}, {'text': 'frontal lobe syndrome', 'type': 'Disease', 'start': 396, 'end': 417, 'mesh': 'D001927'}, {'text': 'carmofur', 'type': 'Chemical', 'start': 608, 'end': 616, 'mesh': 'C017367'}, {'text': 'leukoencephalopathy', 'type': 'Disease', 'start': 625, 'end': 644, 'mesh': 'D056784'}, {'text': 'organic personality syndrome', 'type': 'Disease', 'start': 670, 'end': 698, 'mesh': 'D010554'}, {'text': 'structural damage to the frontal lobe', 'type': 'Disease', 'start': 750, 'end': 787, 'mesh': 'D001927'}]"
+322,6209318,International mexiletine and placebo antiarrhythmic coronary trial: I. Report on arrhythmia and other findings. Impact Research Group.,"The antiarrhythmic effects of the sustained release form of mexiletine (Mexitil-Perlongets) were evaluated in a double-blind placebo trial in 630 patients with recent documented myocardial infarction. The primary response variable was based on central reading of 24 hour ambulatory electrocardiographic recordings and was defined as the occurrence of 30 or more single premature ventricular complexes in any two consecutive 30 minute blocks or one or more runs of two or more premature ventricular complexes in the entire 24 hour electrocardiographic recording. Large differences, regarded as statistically significant, between the mexiletine and placebo groups were noted in that end point at months 1 and 4, but only trends were observed at month 12. These differences were observed even though the serum mexiletine levels obtained in this study were generally lower than those observed in studies that have used the regular form of the drug. There were more deaths in the mexiletine group (7.6%) than in the placebo group (4.8%); the difference was not statistically significant. The incidence of coronary events was similar in both groups. Previously recognized side effects, particularly tremor and gastrointestinal problems, were more frequent in the mexiletine group than in the placebo group.","[{'text': 'mexiletine', 'type': 'Chemical', 'start': 14, 'end': 24, 'mesh': 'D008801'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 81, 'end': 91, 'mesh': 'D001145'}, {'text': 'mexiletine', 'type': 'Chemical', 'start': 195, 'end': 205, 'mesh': 'D008801'}, {'text': 'Mexitil-Perlongets', 'type': 'Chemical', 'start': 207, 'end': 225, 'mesh': 'D008801'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 313, 'end': 334, 'mesh': 'D009203'}, {'text': 'mexiletine', 'type': 'Chemical', 'start': 767, 'end': 777, 'mesh': 'D008801'}, {'text': 'mexiletine', 'type': 'Chemical', 'start': 942, 'end': 952, 'mesh': 'D008801'}, {'text': 'deaths', 'type': 'Disease', 'start': 1096, 'end': 1102, 'mesh': 'D003643'}, {'text': 'mexiletine', 'type': 'Chemical', 'start': 1110, 'end': 1120, 'mesh': 'D008801'}, {'text': 'tremor', 'type': 'Disease', 'start': 1328, 'end': 1334, 'mesh': 'D014202'}, {'text': 'gastrointestinal problems', 'type': 'Disease', 'start': 1339, 'end': 1364, 'mesh': 'D012817'}, {'text': 'mexiletine', 'type': 'Chemical', 'start': 1392, 'end': 1402, 'mesh': 'D008801'}]"
+323,3615541,Regional localization of the antagonism of amphetamine-induced hyperactivity by intracerebral calcitonin injections.,"Calcitonin receptors are found in the brain, and intracerebral infusions of calcitonin can produce behavioral effects. Among these behavioral effects are decreases in food intake and decreases in amphetamine-induced locomotor activity. In previous experiments we found that decreases in food intake were induced by local administration of calcitonin into several hypothalamic sites and into the nucleus accumbens. In the present experiment calcitonin decreased locomotor activity when locally injected into the same sites where it decreases food intake. The areas where calcitonin is most effective in decreasing locomotor activity are located in the hypothalamus and nucleus accumbens, suggesting that these areas are the major sites of action of calcitonin in inhibiting amphetamine-induced locomotor activity.","[{'text': 'amphetamine', 'type': 'Chemical', 'start': 43, 'end': 54, 'mesh': 'D000661'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 63, 'end': 76, 'mesh': 'D006948'}, {'text': 'calcitonin', 'type': 'Chemical', 'start': 94, 'end': 104, 'mesh': 'D002116'}, {'text': 'Calcitonin', 'type': 'Chemical', 'start': 117, 'end': 127, 'mesh': 'D002116'}, {'text': 'calcitonin', 'type': 'Chemical', 'start': 193, 'end': 203, 'mesh': 'D002116'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 313, 'end': 324, 'mesh': 'D000661'}, {'text': 'calcitonin', 'type': 'Chemical', 'start': 456, 'end': 466, 'mesh': 'D002116'}, {'text': 'calcitonin', 'type': 'Chemical', 'start': 557, 'end': 567, 'mesh': 'D002116'}, {'text': 'calcitonin', 'type': 'Chemical', 'start': 687, 'end': 697, 'mesh': 'D002116'}, {'text': 'calcitonin', 'type': 'Chemical', 'start': 865, 'end': 875, 'mesh': 'D002116'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 890, 'end': 901, 'mesh': 'D000661'}]"
+324,8953972,Fatal intracranial bleeding associated with prehospital use of epinephrine.,"We present a case of paramedic misjudgment in the execution of a protocol for the treatment of allergic reaction in a case of pulmonary edema with wheezing. The sudden onset of respiratory distress, rash, and a history of a new medicine led the two paramedics on the scene to administer subcutaneous epinephrine. Subsequently, acute cardiac arrest and fatal subarachnoid hemorrhage occurred. Epinephrine has a proven role in cardiac arrest in prehospital care; however, use by paramedics in patients with suspected allergic reaction and severe hypertension should be viewed with caution.","[{'text': 'intracranial bleeding', 'type': 'Disease', 'start': 6, 'end': 27, 'mesh': 'D013345'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 63, 'end': 74, 'mesh': 'D004837'}, {'text': 'allergic reaction', 'type': 'Disease', 'start': 171, 'end': 188, 'mesh': 'D004342'}, {'text': 'pulmonary edema', 'type': 'Disease', 'start': 202, 'end': 217, 'mesh': 'D011654'}, {'text': 'wheezing', 'type': 'Disease', 'start': 223, 'end': 231, 'mesh': 'D012135'}, {'text': 'respiratory distress', 'type': 'Disease', 'start': 253, 'end': 273, 'mesh': 'D012128'}, {'text': 'rash', 'type': 'Disease', 'start': 275, 'end': 279, 'mesh': 'D005076'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 376, 'end': 387, 'mesh': 'D004837'}, {'text': 'cardiac arrest', 'type': 'Disease', 'start': 409, 'end': 423, 'mesh': 'D006323'}, {'text': 'subarachnoid hemorrhage', 'type': 'Disease', 'start': 434, 'end': 457, 'mesh': 'D013345'}, {'text': 'Epinephrine', 'type': 'Chemical', 'start': 468, 'end': 479, 'mesh': 'D004837'}, {'text': 'cardiac arrest', 'type': 'Disease', 'start': 501, 'end': 515, 'mesh': 'D006323'}, {'text': 'allergic reaction', 'type': 'Disease', 'start': 591, 'end': 608, 'mesh': 'D004342'}, {'text': 'hypertension', 'type': 'Disease', 'start': 620, 'end': 632, 'mesh': 'D006973'}]"
+325,3782049,A case of massive rhabdomyolysis following molindone administration.,"Rhabdomyolysis is a potentially lethal syndrome that psychiatric patients seem predisposed to develop. The clinical signs and symptoms, typical laboratory features, and complications of rhabdomyolysis are presented. The case of a schizophrenic patient is reported to illustrate massive rhabdomyolysis and subsequent acute renal failure following molindone administration. Physicians who prescribe molindone should be aware of this reaction.","[{'text': 'rhabdomyolysis', 'type': 'Disease', 'start': 18, 'end': 32, 'mesh': 'D012206'}, {'text': 'molindone', 'type': 'Chemical', 'start': 43, 'end': 52, 'mesh': 'D008972'}, {'text': 'Rhabdomyolysis', 'type': 'Disease', 'start': 69, 'end': 83, 'mesh': 'D012206'}, {'text': 'psychiatric', 'type': 'Disease', 'start': 122, 'end': 133, 'mesh': 'D001523'}, {'text': 'rhabdomyolysis', 'type': 'Disease', 'start': 255, 'end': 269, 'mesh': 'D012206'}, {'text': 'schizophrenic', 'type': 'Disease', 'start': 299, 'end': 312, 'mesh': 'D012559'}, {'text': 'rhabdomyolysis', 'type': 'Disease', 'start': 355, 'end': 369, 'mesh': 'D012206'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 385, 'end': 404, 'mesh': 'D058186'}, {'text': 'molindone', 'type': 'Chemical', 'start': 415, 'end': 424, 'mesh': 'D008972'}, {'text': 'molindone', 'type': 'Chemical', 'start': 466, 'end': 475, 'mesh': 'D008972'}]"
+326,9100294,Cardiovascular alterations in rat fetuses exposed to calcium channel blockers.,"Preclinical toxicologic investigation suggested that a new calcium channel blocker, Ro 40-5967, induced cardiovascular alterations in rat fetuses exposed to this agent during organogenesis. The present study was designed to investigate the hypothesis that calcium channel blockers in general induce cardiovascular malformations indicating a pharmacologic class effect. We studied three calcium channel blockers of different structure, nifedipine, diltiazem, and verapamil, along with the new agent. Pregnant rats were administered one of these calcium channel blockers during the period of cardiac morphogenesis and the offspring examined on day 20 of gestation for cardiovascular malformations. A low incidence of cardiovascular malformations was observed after exposure to each of the four calcium channel blockers, but this incidence was statistically significant only for verapamil and nifedipine. All four agents were associated with aortic arch branching variants, although significantly increased only for Ro 40-5967 and verapamil.","[{'text': 'Cardiovascular alterations', 'type': 'Disease', 'start': 0, 'end': 26, 'mesh': 'D018376'}, {'text': 'calcium', 'type': 'Chemical', 'start': 53, 'end': 60, 'mesh': 'D002118'}, {'text': 'calcium', 'type': 'Chemical', 'start': 138, 'end': 145, 'mesh': 'D002118'}, {'text': 'Ro 40-5967', 'type': 'Chemical', 'start': 163, 'end': 173, 'mesh': 'D020748'}, {'text': 'cardiovascular alterations', 'type': 'Disease', 'start': 183, 'end': 209, 'mesh': 'D018376'}, {'text': 'calcium', 'type': 'Chemical', 'start': 335, 'end': 342, 'mesh': 'D002118'}, {'text': 'cardiovascular malformations', 'type': 'Disease', 'start': 378, 'end': 406, 'mesh': 'D018376'}, {'text': 'calcium', 'type': 'Chemical', 'start': 465, 'end': 472, 'mesh': 'D002118'}, {'text': 'nifedipine', 'type': 'Chemical', 'start': 514, 'end': 524, 'mesh': 'D009543'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 526, 'end': 535, 'mesh': 'D004110'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 541, 'end': 550, 'mesh': 'D014700'}, {'text': 'calcium', 'type': 'Chemical', 'start': 623, 'end': 630, 'mesh': 'D002118'}, {'text': 'cardiovascular malformations', 'type': 'Disease', 'start': 745, 'end': 773, 'mesh': 'D018376'}, {'text': 'cardiovascular malformations', 'type': 'Disease', 'start': 794, 'end': 822, 'mesh': 'D018376'}, {'text': 'calcium', 'type': 'Chemical', 'start': 871, 'end': 878, 'mesh': 'D002118'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 955, 'end': 964, 'mesh': 'D014700'}, {'text': 'nifedipine', 'type': 'Chemical', 'start': 969, 'end': 979, 'mesh': 'D009543'}, {'text': 'Ro 40-5967', 'type': 'Chemical', 'start': 1092, 'end': 1102, 'mesh': 'D020748'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 1107, 'end': 1116, 'mesh': 'D014700'}]"
+327,19889778,Differential impact of immune escape mutations G145R and P120T on the replication of lamivudine-resistant hepatitis B virus e antigen-positive and -negative strains.,"Immune escape variants of the hepatitis B virus (HBV) represent an emerging clinical challenge, because they can be associated with vaccine escape, HBV reactivation, and failure of diagnostic tests. Recent data suggest a preferential selection of immune escape mutants in distinct peripheral blood leukocyte compartments of infected individuals. We therefore systematically analyzed the functional impact of the most prevalent immune escape variants, the sG145R and sP120T mutants, on the viral replication efficacy and antiviral drug susceptibility of common treatment-associated mutants with resistance to lamivudine (LAM) and/or HBeAg negativity. Replication-competent HBV strains with sG145R or sP120T and LAM resistance (rtM204I or rtL180M/rtM204V) were generated on an HBeAg-positive and an HBeAg-negative background with precore (PC) and basal core promoter (BCP) mutants. The sG145R mutation strongly reduced HBsAg levels and was able to fully restore the impaired replication of LAM-resistant HBV mutants to the levels of wild-type HBV, and PC or BCP mutations further enhanced viral replication. Although the sP120T substitution also impaired HBsAg secretion, it did not enhance the replication of LAM-resistant clones. However, the concomitant occurrence of HBeAg negativity (PC/BCP), sP120T, and LAM resistance resulted in the restoration of replication to levels of wild-type HBV. In all clones with combined immune escape and LAM resistance mutations, the nucleotide analogues adefovir and tenofovir remained effective in suppressing viral replication in vitro. These findings reveal the differential impact of immune escape variants on the replication and drug susceptibility of complex HBV mutants, supporting the need of close surveillance and treatment adjustment in response to the selection of distinct mutational patterns.","[{'text': 'lamivudine', 'type': 'Chemical', 'start': 85, 'end': 95, 'mesh': 'D019259'}, {'text': 'hepatitis B virus e antigen', 'type': 'Chemical', 'start': 106, 'end': 133, 'mesh': 'D006513'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 196, 'end': 207, 'mesh': 'D006509'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 774, 'end': 784, 'mesh': 'D019259'}, {'text': 'LAM', 'type': 'Chemical', 'start': 786, 'end': 789, 'mesh': 'D019259'}, {'text': 'HBeAg', 'type': 'Chemical', 'start': 798, 'end': 803, 'mesh': 'D006513'}, {'text': 'LAM', 'type': 'Chemical', 'start': 876, 'end': 879, 'mesh': 'D019259'}, {'text': 'HBeAg', 'type': 'Chemical', 'start': 941, 'end': 946, 'mesh': 'D006513'}, {'text': 'HBeAg', 'type': 'Chemical', 'start': 963, 'end': 968, 'mesh': 'D006513'}, {'text': 'HBsAg', 'type': 'Chemical', 'start': 1083, 'end': 1088, 'mesh': 'D006514'}, {'text': 'LAM', 'type': 'Chemical', 'start': 1154, 'end': 1157, 'mesh': 'D019259'}, {'text': 'HBsAg', 'type': 'Chemical', 'start': 1319, 'end': 1324, 'mesh': 'D006514'}, {'text': 'LAM', 'type': 'Chemical', 'start': 1374, 'end': 1377, 'mesh': 'D019259'}, {'text': 'HBeAg', 'type': 'Chemical', 'start': 1435, 'end': 1440, 'mesh': 'D006513'}, {'text': 'LAM', 'type': 'Chemical', 'start': 1474, 'end': 1477, 'mesh': 'D019259'}, {'text': 'LAM', 'type': 'Chemical', 'start': 1606, 'end': 1609, 'mesh': 'D019259'}, {'text': 'nucleotide', 'type': 'Chemical', 'start': 1636, 'end': 1646, 'mesh': 'D009711'}, {'text': 'adefovir', 'type': 'Chemical', 'start': 1657, 'end': 1665, 'mesh': 'C053001'}, {'text': 'tenofovir', 'type': 'Chemical', 'start': 1670, 'end': 1679, 'mesh': 'C096918'}]"
+328,15278670,The effects of sevoflurane on lidocaine-induced convulsions.,"The influence of sevoflurane on lidocaine-induced convulsions was studied in cats. The convulsive threshold (mean +/- SD) was 41.4 +/- 6.5 mg. l(-1) with lidocaine infusion (6 mg.kg(-1).min(-1)), increasing significantly to 66.6 +/- 10.9 mg. l(-1) when the end-tidal concentration of sevoflurane was 0.8%. However, the threshold (61.6 +/- 8.7 mg. l(-1)) during 1.6% sevoflurane was not significant from that during 0.8% sevoflurane, indicating a celling effect. There was no significant difference in the convulsive threshold between sevoflurane and enflurane. The rise in blood pressure became less marked when higher concentrations of sevoflurane or enflurane were administered and the blood pressure at convulsions decreased significantly in 1.6% sevoflurane, and in 0.8% and 1.6% enflurane. However, there was no significant difference in the lidocaine concentrations measured when the systolic blood pressure became 70 mmHg. Apamin, a selective blocker of calcium-dependent potassium channels, was administered intracerebroventricularly in rats anesthetized with 0.8% sevoflurane to investigate the mechanism of the anticonvulsive effects. Apamin (10 ng) had a tendency to decrease the convulsive threshold (21.6 +/- 2.2 to 19.9 +/- 2.5 mg. l(-1)) but this was not statistically significant. It is suggested that sevoflurane reduces the convulsive effect of lidocaine toxicity but carries some risk due to circulatory depression.","[{'text': 'sevoflurane', 'type': 'Chemical', 'start': 15, 'end': 26, 'mesh': 'C009250'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 30, 'end': 39, 'mesh': 'D008012'}, {'text': 'convulsions', 'type': 'Disease', 'start': 48, 'end': 59, 'mesh': 'D012640'}, {'text': 'sevoflurane', 'type': 'Chemical', 'start': 78, 'end': 89, 'mesh': 'C009250'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 93, 'end': 102, 'mesh': 'D008012'}, {'text': 'convulsions', 'type': 'Disease', 'start': 111, 'end': 122, 'mesh': 'D012640'}, {'text': 'convulsive', 'type': 'Disease', 'start': 148, 'end': 158, 'mesh': 'D012640'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 215, 'end': 224, 'mesh': 'D008012'}, {'text': 'sevoflurane', 'type': 'Chemical', 'start': 345, 'end': 356, 'mesh': 'C009250'}, {'text': 'sevoflurane', 'type': 'Chemical', 'start': 427, 'end': 438, 'mesh': 'C009250'}, {'text': 'sevoflurane', 'type': 'Chemical', 'start': 481, 'end': 492, 'mesh': 'C009250'}, {'text': 'convulsive', 'type': 'Disease', 'start': 566, 'end': 576, 'mesh': 'D012640'}, {'text': 'sevoflurane', 'type': 'Chemical', 'start': 595, 'end': 606, 'mesh': 'C009250'}, {'text': 'enflurane', 'type': 'Chemical', 'start': 611, 'end': 620, 'mesh': 'D004737'}, {'text': 'sevoflurane', 'type': 'Chemical', 'start': 698, 'end': 709, 'mesh': 'C009250'}, {'text': 'enflurane', 'type': 'Chemical', 'start': 713, 'end': 722, 'mesh': 'D004737'}, {'text': 'convulsions', 'type': 'Disease', 'start': 767, 'end': 778, 'mesh': 'D012640'}, {'text': 'sevoflurane', 'type': 'Chemical', 'start': 811, 'end': 822, 'mesh': 'C009250'}, {'text': 'enflurane', 'type': 'Chemical', 'start': 845, 'end': 854, 'mesh': 'D004737'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 908, 'end': 917, 'mesh': 'D008012'}, {'text': 'Apamin', 'type': 'Chemical', 'start': 991, 'end': 997, 'mesh': 'D001030'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1022, 'end': 1029, 'mesh': 'D002118'}, {'text': 'potassium', 'type': 'Chemical', 'start': 1040, 'end': 1049, 'mesh': 'D011188'}, {'text': 'sevoflurane', 'type': 'Chemical', 'start': 1134, 'end': 1145, 'mesh': 'C009250'}, {'text': 'Apamin', 'type': 'Chemical', 'start': 1206, 'end': 1212, 'mesh': 'D001030'}, {'text': 'convulsive', 'type': 'Disease', 'start': 1252, 'end': 1262, 'mesh': 'D012640'}, {'text': 'sevoflurane', 'type': 'Chemical', 'start': 1379, 'end': 1390, 'mesh': 'C009250'}, {'text': 'convulsive', 'type': 'Disease', 'start': 1403, 'end': 1413, 'mesh': 'D012640'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 1424, 'end': 1433, 'mesh': 'D008012'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1434, 'end': 1442, 'mesh': 'D064420'}, {'text': 'depression', 'type': 'Disease', 'start': 1484, 'end': 1494, 'mesh': 'D003866'}]"
+329,17042910,Anti-oxidant effects of atorvastatin in dexamethasone-induced hypertension in the rat.,"1. Dexamethasone (Dex)-induced hypertension is characterized by endothelial dysfunction associated with nitric oxide (NO) deficiency and increased superoxide (O2-) production. Atorvastatin (Ato) possesses pleiotropic properties that have been reported to improve endothelial function through increased availability of NO and reduced O2- production in various forms of hypertension. In the present study, we investigated whether 50 mg/kg per day, p.o., Ato could prevent endothelial NO synthase (eNOS) downregulation and the increase in O2- in Sprague-Dawley (SD) rats, thereby reducing blood pressure. 2. Male SD rats (n = 30) were treated with Ato (50 mg/kg per day in drinking water) or tap water for 15 days. Dexamethasone (10 microg/kg per day, s.c.) or saline was started after 4 days in Ato-treated and non-treated rats and continued for 11-13 days. Systolic blood pressure (SBP) was measured on alternate days using the tail-cuff method. Endothelial function was assessed by acetylcholine-induced vasorelaxation and phenylephrine-induced vasoconstriction in aortic segments. Vascular eNOS mRNA was assessed by semi-quantitative reverse transcription-polymerase chain reaction. 3. In rats treated with Dex alone, SBP was increased from 109 +/- 2 to 133 +/- 2 mmHg on Days 4 and Day 14, respectively (P < 0.001). In the Ato + Dex group, SBP was increased from 113 +/- 2 to 119 +/- 2 mmHg on Days 4 to 14, respectively (P < 0.001), but was significantly lower than SBP in the group treated with Dex alone (P < 0.05). Endothelial-dependent relaxation and eNOS mRNA expression were greater in the Dex + Ato group than in the Dex only group (P < 0.05 and P < 0.0001, respectively). Aortic superoxide production was lower in the Dex + Ato group compared with the group treated with Dex alone (P < 0.0001). 4. Treatment with Ato improved endothelial function, reduced superoxide production and reduced SBP in Dex-treated SD rats.","[{'text': 'atorvastatin', 'type': 'Chemical', 'start': 24, 'end': 36, 'mesh': 'C065179'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 40, 'end': 53, 'mesh': 'D003907'}, {'text': 'hypertension', 'type': 'Disease', 'start': 62, 'end': 74, 'mesh': 'D006973'}, {'text': 'Dexamethasone', 'type': 'Chemical', 'start': 90, 'end': 103, 'mesh': 'D003907'}, {'text': 'Dex', 'type': 'Chemical', 'start': 105, 'end': 108, 'mesh': 'D003907'}, {'text': 'hypertension', 'type': 'Disease', 'start': 118, 'end': 130, 'mesh': 'D006973'}, {'text': 'nitric oxide', 'type': 'Chemical', 'start': 191, 'end': 203, 'mesh': 'D009569'}, {'text': 'NO', 'type': 'Chemical', 'start': 205, 'end': 207, 'mesh': 'D009569'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 234, 'end': 244, 'mesh': 'D013481'}, {'text': 'O2-', 'type': 'Chemical', 'start': 246, 'end': 249, 'mesh': 'D013481'}, {'text': 'Atorvastatin', 'type': 'Chemical', 'start': 263, 'end': 275, 'mesh': 'C065179'}, {'text': 'Ato', 'type': 'Chemical', 'start': 277, 'end': 280, 'mesh': 'C065179'}, {'text': 'NO', 'type': 'Chemical', 'start': 405, 'end': 407, 'mesh': 'D009569'}, {'text': 'O2-', 'type': 'Chemical', 'start': 420, 'end': 423, 'mesh': 'D013481'}, {'text': 'hypertension', 'type': 'Disease', 'start': 455, 'end': 467, 'mesh': 'D006973'}, {'text': 'Ato', 'type': 'Chemical', 'start': 539, 'end': 542, 'mesh': 'C065179'}, {'text': 'NO', 'type': 'Chemical', 'start': 569, 'end': 571, 'mesh': 'D009569'}, {'text': 'O2-', 'type': 'Chemical', 'start': 623, 'end': 626, 'mesh': 'D013481'}, {'text': 'Ato', 'type': 'Chemical', 'start': 732, 'end': 735, 'mesh': 'C065179'}, {'text': 'Dexamethasone', 'type': 'Chemical', 'start': 799, 'end': 812, 'mesh': 'D003907'}, {'text': 'Ato', 'type': 'Chemical', 'start': 880, 'end': 883, 'mesh': 'C065179'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 1069, 'end': 1082, 'mesh': 'D000109'}, {'text': 'phenylephrine', 'type': 'Chemical', 'start': 1110, 'end': 1123, 'mesh': 'D010656'}, {'text': 'Dex', 'type': 'Chemical', 'start': 1295, 'end': 1298, 'mesh': 'D003907'}, {'text': 'Ato', 'type': 'Chemical', 'start': 1412, 'end': 1415, 'mesh': 'C065179'}, {'text': 'Dex', 'type': 'Chemical', 'start': 1418, 'end': 1421, 'mesh': 'D003907'}, {'text': 'Dex', 'type': 'Chemical', 'start': 1586, 'end': 1589, 'mesh': 'D003907'}, {'text': 'Dex', 'type': 'Chemical', 'start': 1686, 'end': 1689, 'mesh': 'D003907'}, {'text': 'Ato', 'type': 'Chemical', 'start': 1692, 'end': 1695, 'mesh': 'C065179'}, {'text': 'Dex', 'type': 'Chemical', 'start': 1714, 'end': 1717, 'mesh': 'D003907'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 1777, 'end': 1787, 'mesh': 'D013481'}, {'text': 'Dex', 'type': 'Chemical', 'start': 1816, 'end': 1819, 'mesh': 'D003907'}, {'text': 'Ato', 'type': 'Chemical', 'start': 1822, 'end': 1825, 'mesh': 'C065179'}, {'text': 'Dex', 'type': 'Chemical', 'start': 1869, 'end': 1872, 'mesh': 'D003907'}, {'text': 'Ato', 'type': 'Chemical', 'start': 1911, 'end': 1914, 'mesh': 'C065179'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 1954, 'end': 1964, 'mesh': 'D013481'}, {'text': 'Dex', 'type': 'Chemical', 'start': 1995, 'end': 1998, 'mesh': 'D003907'}]"
+330,11897407,99mTc-glucarate for detection of isoproterenol-induced myocardial infarction in rats.,"Infarct-avid radiopharmaceuticals are necessary for rapid and timely diagnosis of acute myocardial infarction. The animal model used to produce infarction implies artery ligation but chemical induction can be easily obtained with isoproterenol. A new infarct-avid radiopharmaceutical based on glucaric acid was prepared in the hospital radiopharmacy of the INCMNSZ. 99mTc-glucarate was easy to prepare, stable for 96 h and was used to study its biodistribution in rats with isoproterenol-induced acute myocardial infarction. Histological studies demonstrated that the rats developed an infarct 18 h after isoproterenol administration. The rat biodistribution studies showed a rapid blood clearance via the kidneys. Thirty minutes after 99mTc-glucarate administration the standardised heart uptake value S(h)UV was 4.7 in infarcted rat heart which is six times more than in normal rats. ROIs drawn over the gamma camera images showed a ratio of 4.4. The high image quality suggests that high contrast images can be obtained in humans and the 96 h stability makes it an ideal agent to detect, in patients, early cardiac infarction.","[{'text': '99mTc-glucarate', 'type': 'Chemical', 'start': 0, 'end': 15, 'mesh': 'C067171'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 33, 'end': 46, 'mesh': 'D007545'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 55, 'end': 76, 'mesh': 'D009203'}, {'text': 'Infarct', 'type': 'Disease', 'start': 86, 'end': 93, 'mesh': 'D007238'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 174, 'end': 195, 'mesh': 'D009203'}, {'text': 'infarction', 'type': 'Disease', 'start': 230, 'end': 240, 'mesh': 'D007238'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 316, 'end': 329, 'mesh': 'D007545'}, {'text': 'infarct', 'type': 'Disease', 'start': 337, 'end': 344, 'mesh': 'D007238'}, {'text': 'glucaric acid', 'type': 'Chemical', 'start': 379, 'end': 392, 'mesh': 'D005937'}, {'text': '99mTc-glucarate', 'type': 'Chemical', 'start': 452, 'end': 467, 'mesh': 'C067171'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 560, 'end': 573, 'mesh': 'D007545'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 588, 'end': 609, 'mesh': 'D009203'}, {'text': 'infarct', 'type': 'Disease', 'start': 672, 'end': 679, 'mesh': 'D007238'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 691, 'end': 704, 'mesh': 'D007545'}, {'text': '99mTc-glucarate', 'type': 'Chemical', 'start': 822, 'end': 837, 'mesh': 'C067171'}, {'text': 'cardiac infarction', 'type': 'Disease', 'start': 1196, 'end': 1214, 'mesh': 'D009203'}]"
+331,9812111,"A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer's disease.","OBJECTIVE: The goal of this study was to compare the efficacy and side effects of two doses of haloperidol and placebo in the treatment of psychosis and disruptive behaviors in patients with Alzheimer's disease. METHOD: In a 6-week random-assignment, double-blind, placebo-controlled trial (phase A), haloperidol, 2-3 mg/day (standard dose), and haloperidol, 0.50-0.75 mg/day (low dose), were compared in 71 outpatients with Alzheimer's disease. For the subsequent 6-week double-blind crossover phase (phase B), patients taking standard- or low-dose haloperidol were switched to placebo, and patients taking placebo were randomly assigned to standard- or low-dose haloperidol. RESULTS: For the 60 patients who completed phase A, standard-dose haloperidol was efficacious and superior to both low-dose haloperidol and placebo for scores on the Brief Psychiatric Rating Scale psychosis factor and on psychomotor agitation. Response rates according to three sets of criteria were greater with the standard dose (55%-60%) than the low dose (25%-35%) and placebo (25%-30%). The advantage of standard dose over low dose was replicated in phase B. In phase A, extrapyramidal signs tended to be greater with the standard dose than in the other two conditions, primarily because of a subgroup (20%) who developed moderate to severe signs. Low-dose haloperidol did not differ from placebo on any measure of efficacy or side effects. CONCLUSIONS: The results indicated a favorable therapeutic profile for haloperidol in doses of 2-3 mg/day, although a subgroup developed moderate to severe extrapyramidal signs. A starting dose of 1 mg/day with gradual, upward dose titration is recommended. The narrow therapeutic window observed with haloperidol may also apply to other neuroleptics used in Alzheimer's disease patients with psychosis and disruptive behaviors.","[{'text': 'haloperidol', 'type': 'Chemical', 'start': 58, 'end': 69, 'mesh': 'D006220'}, {'text': 'psychosis', 'type': 'Disease', 'start': 74, 'end': 83, 'mesh': 'D011618'}, {'text': 'disruptive behaviors', 'type': 'Disease', 'start': 88, 'end': 108, 'mesh': 'D019958'}, {'text': ""Alzheimer's disease"", 'type': 'Disease', 'start': 112, 'end': 131, 'mesh': 'D000544'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 228, 'end': 239, 'mesh': 'D006220'}, {'text': 'psychosis', 'type': 'Disease', 'start': 272, 'end': 281, 'mesh': 'D011618'}, {'text': 'disruptive behaviors', 'type': 'Disease', 'start': 286, 'end': 306, 'mesh': 'D019958'}, {'text': ""Alzheimer's disease"", 'type': 'Disease', 'start': 324, 'end': 343, 'mesh': 'D000544'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 434, 'end': 445, 'mesh': 'D006220'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 479, 'end': 490, 'mesh': 'D006220'}, {'text': ""Alzheimer's disease"", 'type': 'Disease', 'start': 558, 'end': 577, 'mesh': 'D000544'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 683, 'end': 694, 'mesh': 'D006220'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 797, 'end': 808, 'mesh': 'D006220'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 876, 'end': 887, 'mesh': 'D006220'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 934, 'end': 945, 'mesh': 'D006220'}, {'text': 'psychosis', 'type': 'Disease', 'start': 1007, 'end': 1016, 'mesh': 'D011618'}, {'text': 'psychomotor agitation', 'type': 'Disease', 'start': 1031, 'end': 1052, 'mesh': 'D011595'}, {'text': 'extrapyramidal signs', 'type': 'Disease', 'start': 1286, 'end': 1306, 'mesh': 'D001480'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1472, 'end': 1483, 'mesh': 'D006220'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1627, 'end': 1638, 'mesh': 'D006220'}, {'text': 'extrapyramidal signs', 'type': 'Disease', 'start': 1712, 'end': 1732, 'mesh': 'D001480'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1858, 'end': 1869, 'mesh': 'D006220'}, {'text': ""Alzheimer's disease"", 'type': 'Disease', 'start': 1915, 'end': 1934, 'mesh': 'D000544'}, {'text': 'psychosis', 'type': 'Disease', 'start': 1949, 'end': 1958, 'mesh': 'D011618'}, {'text': 'disruptive behaviors', 'type': 'Disease', 'start': 1963, 'end': 1983, 'mesh': 'D019958'}]"
+332,15572383,Individual differences in renal ACE activity in healthy rats predict susceptibility to adriamycin-induced renal damage.,"BACKGROUND: In man, differences in angiotensin-converting enzyme (ACE) levels, related to ACE (I/D) genotype, are associated with renal prognosis. This raises the hypothesis that individual differences in renal ACE activity are involved in renal susceptibility to inflicted damage. Therefore, we studied the predictive effect of renal ACE activity for the severity of renal damage induced by a single injection of adriamycin in rats. METHODS: Renal ACE activity (Hip-His-Leu cleavage by cortical homogenates) was determined by renal biopsy in 27 adult male Wistar rats. After 1 week of recovery, proteinuria was induced by adriamycin [1.5 mg/kg intravenously (i.v.) n = 18; controls, saline i.v. n = 9]. Proteinuria was measured every 2 weeks. After 12 weeks, rats were sacrificed and their kidneys harvested. RESULTS: As anticipated, adriamycin elicited nephrotic range proteinuria, renal interstitial damage and mild focal glomerulosclerosis. Baseline renal ACE positively correlated with the relative rise in proteinuria after adriamycin (r = 0.62, P<0.01), renal interstitial alpha-smooth muscle actin (r = 0.49, P<0.05), interstitial macrophage influx (r = 0.56, P<0.05), interstitial collagen III (r = 0.53, P<0.05), glomerular alpha-smooth muscle actin (r = 0.74, P<0.01) and glomerular desmin (r = 0.48, P<0.05). Baseline renal ACE did not correlate with focal glomerulosclerosis (r = 0.22, NS). In controls, no predictive values for renal parameters were observed. CONCLUSION: Individual differences in renal ACE activity predict the severity of adriamycin-induced renal damage in this outbred rat strain. This supports the assumption that differences in renal ACE activity predispose to a less favourable course of renal damage.","[{'text': 'adriamycin', 'type': 'Chemical', 'start': 87, 'end': 97, 'mesh': 'D004317'}, {'text': 'renal damage', 'type': 'Disease', 'start': 106, 'end': 118, 'mesh': 'D007674'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 155, 'end': 166, 'mesh': 'D000809'}, {'text': 'renal damage', 'type': 'Disease', 'start': 488, 'end': 500, 'mesh': 'D007674'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 534, 'end': 544, 'mesh': 'D004317'}, {'text': 'Hip-His-Leu', 'type': 'Chemical', 'start': 583, 'end': 594, 'mesh': 'C010980'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 716, 'end': 727, 'mesh': 'D011507'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 743, 'end': 753, 'mesh': 'D004317'}, {'text': 'Proteinuria', 'type': 'Disease', 'start': 824, 'end': 835, 'mesh': 'D011507'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 955, 'end': 965, 'mesh': 'D004317'}, {'text': 'nephrotic', 'type': 'Disease', 'start': 975, 'end': 984, 'mesh': 'D009404'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 991, 'end': 1002, 'mesh': 'D011507'}, {'text': 'renal interstitial damage', 'type': 'Disease', 'start': 1004, 'end': 1029, 'mesh': 'D007674'}, {'text': 'focal glomerulosclerosis', 'type': 'Disease', 'start': 1039, 'end': 1063, 'mesh': 'D005923'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1132, 'end': 1143, 'mesh': 'D011507'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 1150, 'end': 1160, 'mesh': 'D004317'}, {'text': 'focal glomerulosclerosis', 'type': 'Disease', 'start': 1483, 'end': 1507, 'mesh': 'D005923'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 1675, 'end': 1685, 'mesh': 'D004317'}, {'text': 'renal damage', 'type': 'Disease', 'start': 1694, 'end': 1706, 'mesh': 'D007674'}, {'text': 'renal damage', 'type': 'Disease', 'start': 1845, 'end': 1857, 'mesh': 'D007674'}]"
+333,7420681,Clinical nephrotoxicity of tobramycin and gentamicin. A prospective study.,"Nearly 3.2 million people in this country receive aminoglycoside antibiotics annually. Gentamicin sulfate and tobramycin sulfate continue to demonstrate ototoxicity and nephrotoxicity in both animal and clinical studies. In this study, 62 patients with confirmed initial normal renal function and treated with 2 to 5 mg/kg/day of gentamicin sulfate or tobramycin sulfate for a minimum of seven days were followed up prospectively for the development of aminoglycoside-related renal failure, defined as at least a one-third reduction in renal function. In these 62 patients, no other causes for renal failure could be identified. Five of 33 (15%) of the tobramycin-treated patients and 16 of 29 (55.2%) of the gentamicin-treated patients had renal failure. Thus, gentamicin was associated with renal failure more than three times as often as was tobramycin.","[{'text': 'nephrotoxicity', 'type': 'Disease', 'start': 9, 'end': 23, 'mesh': 'D007674'}, {'text': 'tobramycin', 'type': 'Chemical', 'start': 27, 'end': 37, 'mesh': 'D014031'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 42, 'end': 52, 'mesh': 'D005839'}, {'text': 'aminoglycoside', 'type': 'Chemical', 'start': 125, 'end': 139, 'mesh': 'D000617'}, {'text': 'Gentamicin sulfate', 'type': 'Chemical', 'start': 162, 'end': 180, 'mesh': 'D005839'}, {'text': 'tobramycin sulfate', 'type': 'Chemical', 'start': 185, 'end': 203, 'mesh': 'D014031'}, {'text': 'ototoxicity', 'type': 'Disease', 'start': 228, 'end': 239, 'mesh': 'D006311'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 244, 'end': 258, 'mesh': 'D007674'}, {'text': 'gentamicin sulfate', 'type': 'Chemical', 'start': 405, 'end': 423, 'mesh': 'D005839'}, {'text': 'tobramycin sulfate', 'type': 'Chemical', 'start': 427, 'end': 445, 'mesh': 'D014031'}, {'text': 'aminoglycoside', 'type': 'Chemical', 'start': 528, 'end': 542, 'mesh': 'D000617'}, {'text': 'renal failure', 'type': 'Disease', 'start': 551, 'end': 564, 'mesh': 'D051437'}, {'text': 'renal failure', 'type': 'Disease', 'start': 669, 'end': 682, 'mesh': 'D051437'}, {'text': 'tobramycin', 'type': 'Chemical', 'start': 728, 'end': 738, 'mesh': 'D014031'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 784, 'end': 794, 'mesh': 'D005839'}, {'text': 'renal failure', 'type': 'Disease', 'start': 816, 'end': 829, 'mesh': 'D051437'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 837, 'end': 847, 'mesh': 'D005839'}, {'text': 'renal failure', 'type': 'Disease', 'start': 868, 'end': 881, 'mesh': 'D051437'}, {'text': 'tobramycin', 'type': 'Chemical', 'start': 920, 'end': 930, 'mesh': 'D014031'}]"
+334,12907309,"Neuroprotective action of MPEP, a selective mGluR5 antagonist, in methamphetamine-induced dopaminergic neurotoxicity is associated with a decrease in dopamine outflow and inhibition of hyperthermia in rats.","The aim of this study was to examine the role of metabotropic glutamate receptor 5 (mGluR5) in the toxic action of methamphetamine on dopaminergic neurones in rats. Methamphetamine (10 mg/kg sc), administered five times, reduced the levels of dopamine and its metabolites in striatal tissue when measured 72 h after the last injection. A selective antagonist of mGluR5, 2-methyl-6-(phenylethynyl)pyridine (MPEP; 5 mg/kg ip), when administered five times immediately before each methamphetamine injection reversed the above-mentioned methamphetamine effects. A single MPEP (5 mg/kg ip) injection reduced the basal extracellular dopamine level in the striatum, as well as dopamine release stimulated either by methamphetamine (10 mg/kg sc) or by intrastriatally administered veratridine (100 microM). Moreover, it transiently diminished the methamphetamine (10 mg/kg sc)-induced hyperthermia and reduced basal body temperature. MPEP administered into the striatum at high concentrations (500 microM) increased extracellular dopamine levels, while lower concentrations (50-100 microM) were devoid of any effect. The results of this study suggest that the blockade of mGluR5 by MPEP may protect dopaminergic neurones against methamphetamine-induced toxicity. Neuroprotection rendered by MPEP may be associated with the reduction of the methamphetamine-induced dopamine efflux in the striatum due to the blockade of extrastriatal mGluR5, and with a decrease in hyperthermia.","[{'text': 'MPEP', 'type': 'Chemical', 'start': 26, 'end': 30, 'mesh': 'C121465'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 66, 'end': 81, 'mesh': 'D008694'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 103, 'end': 116, 'mesh': 'D020258'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 150, 'end': 158, 'mesh': 'D004298'}, {'text': 'hyperthermia', 'type': 'Disease', 'start': 185, 'end': 197, 'mesh': 'D005334'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 269, 'end': 278, 'mesh': 'D018698'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 322, 'end': 337, 'mesh': 'D008694'}, {'text': 'Methamphetamine', 'type': 'Chemical', 'start': 372, 'end': 387, 'mesh': 'D008694'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 450, 'end': 458, 'mesh': 'D004298'}, {'text': '2-methyl-6-(phenylethynyl)pyridine', 'type': 'Chemical', 'start': 577, 'end': 611, 'mesh': 'C121465'}, {'text': 'MPEP', 'type': 'Chemical', 'start': 613, 'end': 617, 'mesh': 'C121465'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 685, 'end': 700, 'mesh': 'D008694'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 740, 'end': 755, 'mesh': 'D008694'}, {'text': 'MPEP', 'type': 'Chemical', 'start': 774, 'end': 778, 'mesh': 'C121465'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 834, 'end': 842, 'mesh': 'D004298'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 877, 'end': 885, 'mesh': 'D004298'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 915, 'end': 930, 'mesh': 'D008694'}, {'text': 'veratridine', 'type': 'Chemical', 'start': 980, 'end': 991, 'mesh': 'D014701'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 1046, 'end': 1061, 'mesh': 'D008694'}, {'text': 'hyperthermia', 'type': 'Disease', 'start': 1084, 'end': 1096, 'mesh': 'D005334'}, {'text': 'MPEP', 'type': 'Chemical', 'start': 1133, 'end': 1137, 'mesh': 'C121465'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1229, 'end': 1237, 'mesh': 'D004298'}, {'text': 'MPEP', 'type': 'Chemical', 'start': 1381, 'end': 1385, 'mesh': 'C121465'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 1428, 'end': 1443, 'mesh': 'D008694'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1452, 'end': 1460, 'mesh': 'D064420'}, {'text': 'MPEP', 'type': 'Chemical', 'start': 1490, 'end': 1494, 'mesh': 'C121465'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 1539, 'end': 1554, 'mesh': 'D008694'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1563, 'end': 1571, 'mesh': 'D004298'}, {'text': 'hyperthermia', 'type': 'Disease', 'start': 1663, 'end': 1675, 'mesh': 'D005334'}]"
+335,16680561,Pharmacokinetics of desipramine HCl when administered with cinacalcet HCl.,"OBJECTIVE: In vitro work has demonstrated that cinacalcet is a strong inhibitor of cytochrome P450 isoenzyme (CYP) 2D6. The purpose of this study was to evaluate the effect of cinacalcet on CYP2D6 activity, using desipramine as a probe substrate, in healthy subjects. METHODS: Seventeen subjects who were genotyped as CYP2D6 extensive metabolizers were enrolled in this randomized, open-label, crossover study to receive a single oral dose of desipramine (50 mg) on two separate occasions, once alone and once after multiple doses of cinacalcet (90 mg for 7 days). Blood samples were obtained predose and up to 72 h postdose. RESULTS: Fourteen subjects completed both treatment arms. Relative to desipramine alone, mean AUC and C(max) of desipramine increased 3.6- and 1.8-fold when coadministered with cinacalcet. The t (1/2,z) of desipramine was longer when desipramine was coadministered with cinacalcet (21.0 versus 43.3 hs). The t (max) was similar between the regimens. Fewer subjects reported adverse events following treatment with desipramine alone than when receiving desipramine with cinacalcet (33 versus 86%), the most frequent of which (nausea and headache) have been reported for patients treated with either desipramine or cinacalcet. CONCLUSION: This study demonstrates that cinacalcet is a strong inhibitor of CYP2D6. These data suggest that during concomitant treatment with cinacalcet, dose adjustment may be necessary for drugs that demonstrate a narrow therapeutic index and are metabolized by CYP2D6.","[{'text': 'desipramine HCl', 'type': 'Chemical', 'start': 20, 'end': 35, 'mesh': 'D003891'}, {'text': 'cinacalcet HCl', 'type': 'Chemical', 'start': 59, 'end': 73, 'mesh': 'C476217'}, {'text': 'cinacalcet', 'type': 'Chemical', 'start': 122, 'end': 132, 'mesh': 'C476217'}, {'text': 'cinacalcet', 'type': 'Chemical', 'start': 251, 'end': 261, 'mesh': 'C476217'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 288, 'end': 299, 'mesh': 'D003891'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 518, 'end': 529, 'mesh': 'D003891'}, {'text': 'cinacalcet', 'type': 'Chemical', 'start': 609, 'end': 619, 'mesh': 'C476217'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 771, 'end': 782, 'mesh': 'D003891'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 813, 'end': 824, 'mesh': 'D003891'}, {'text': 'cinacalcet', 'type': 'Chemical', 'start': 878, 'end': 888, 'mesh': 'C476217'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 907, 'end': 918, 'mesh': 'D003891'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 935, 'end': 946, 'mesh': 'D003891'}, {'text': 'cinacalcet', 'type': 'Chemical', 'start': 971, 'end': 981, 'mesh': 'C476217'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 1115, 'end': 1126, 'mesh': 'D003891'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 1153, 'end': 1164, 'mesh': 'D003891'}, {'text': 'cinacalcet', 'type': 'Chemical', 'start': 1170, 'end': 1180, 'mesh': 'C476217'}, {'text': 'nausea', 'type': 'Disease', 'start': 1226, 'end': 1232, 'mesh': 'D009325'}, {'text': 'headache', 'type': 'Disease', 'start': 1237, 'end': 1245, 'mesh': 'D006261'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 1299, 'end': 1310, 'mesh': 'D003891'}, {'text': 'cinacalcet', 'type': 'Chemical', 'start': 1314, 'end': 1324, 'mesh': 'C476217'}, {'text': 'cinacalcet', 'type': 'Chemical', 'start': 1367, 'end': 1377, 'mesh': 'C476217'}, {'text': 'cinacalcet', 'type': 'Chemical', 'start': 1469, 'end': 1479, 'mesh': 'C476217'}]"
+336,17532790,Proteomic analysis of striatal proteins in the rat model of L-DOPA-induced dyskinesia.,"L-DOPA-induced dyskinesia (LID) is among the motor complications that arise in Parkinson's disease (PD) patients after a prolonged treatment with L-DOPA. To this day, transcriptome analysis has been performed in a rat model of LID [Neurobiol. Dis., 17 (2004), 219] but information regarding the proteome is still lacking. In the present study, we investigated the changes occurring at the protein level in striatal samples obtained from the unilaterally 6-hydroxydopamine-lesion rat model of PD treated with saline, L-DOPA or bromocriptine using two-dimensional difference gel electrophoresis and mass spectrometry (MS). Rats treated with L-DOPA were allocated to two groups based on the presence or absence of LID. Among the 2000 spots compared for statistical difference, 67 spots were significantly changed in abundance and identified using matrix-assisted laser desorption/ionization time-of-flight MS, atmospheric pressure matrix-assisted laser desorption/ionization and HPLC coupled tandem MS (LC/MS/MS). Out of these 67 proteins, LID significantly changed the expression level of five proteins: alphabeta-crystalin, gamma-enolase, guanidoacetate methyltransferase, vinculin, and proteasome alpha-2 subunit. Complementary techniques such as western immunoblotting and immunohistochemistry were performed to investigate the validity of the data obtained using the proteomic approach. In conclusion, this study provides new insights into the protein changes occurring in LID.","[{'text': 'L-DOPA', 'type': 'Chemical', 'start': 60, 'end': 66, 'mesh': 'D007980'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 75, 'end': 85, 'mesh': 'D004409'}, {'text': 'L-DOPA', 'type': 'Chemical', 'start': 87, 'end': 93, 'mesh': 'D007980'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 102, 'end': 112, 'mesh': 'D004409'}, {'text': 'LID', 'type': 'Disease', 'start': 114, 'end': 117, 'mesh': 'D004409'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 166, 'end': 185, 'mesh': 'D010300'}, {'text': 'PD', 'type': 'Disease', 'start': 187, 'end': 189, 'mesh': 'D010300'}, {'text': 'L-DOPA', 'type': 'Chemical', 'start': 233, 'end': 239, 'mesh': 'D007980'}, {'text': 'LID', 'type': 'Disease', 'start': 314, 'end': 317, 'mesh': 'D004409'}, {'text': '6-hydroxydopamine', 'type': 'Chemical', 'start': 541, 'end': 558, 'mesh': 'D016627'}, {'text': 'PD', 'type': 'Disease', 'start': 579, 'end': 581, 'mesh': 'D010300'}, {'text': 'L-DOPA', 'type': 'Chemical', 'start': 603, 'end': 609, 'mesh': 'D007980'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 613, 'end': 626, 'mesh': 'D001971'}, {'text': 'L-DOPA', 'type': 'Chemical', 'start': 726, 'end': 732, 'mesh': 'D007980'}, {'text': 'LID', 'type': 'Disease', 'start': 798, 'end': 801, 'mesh': 'D004409'}, {'text': 'LID', 'type': 'Disease', 'start': 1124, 'end': 1127, 'mesh': 'D004409'}, {'text': 'LID', 'type': 'Disease', 'start': 1562, 'end': 1565, 'mesh': 'D004409'}]"
+337,7582165,Pseudo-allergic reactions to corticosteroids: diagnosis and alternatives.,"Two patients treated with parenteral paramethasone (Triniol) and dexamethasone (Sedionbel) are described. A few minutes after administration of the drugs, they presented urticaria (patients 1 and 2) and conjunctivitis (patient 1). The purpose of our study was to determine the cause of the patients' reactions, the immunological mechanisms involved and whether these patients would be able to tolerate any kind of corticoid. Clinical examinations and skin, oral and parenteral challenges with different corticosteroids and ELISA tests were performed. In the two patients, skin and ELISA tests with paramethasone were negative, as was the prick test with each of its excipients. A single-blind parenteral challenge with Triniol was positive in both patients after the administration of 1 ml of the drug, and negative with its excipients. We also carried out oral and parenteral challenges with other corticosteroids and found intolerance to some of them. These results suggest that paramethasone caused pseudoallergic reactions in our patients. Corticosteroids different from paramethasone also produced hypersensitivity reactions in these patients; however, a few of them were tolerated. The basic mechanisms of those reactions are not yet fully understood. To our knowledge, this is the first report of a pseudo-allergy caused by paramethasone.","[{'text': 'allergic reactions', 'type': 'Disease', 'start': 7, 'end': 25, 'mesh': 'D004342'}, {'text': 'corticosteroids', 'type': 'Chemical', 'start': 29, 'end': 44, 'mesh': 'D000305'}, {'text': 'paramethasone', 'type': 'Chemical', 'start': 111, 'end': 124, 'mesh': 'D010248'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 139, 'end': 152, 'mesh': 'D003907'}, {'text': 'urticaria', 'type': 'Disease', 'start': 244, 'end': 253, 'mesh': 'D014581'}, {'text': 'conjunctivitis', 'type': 'Disease', 'start': 277, 'end': 291, 'mesh': 'D003231'}, {'text': 'corticosteroids', 'type': 'Chemical', 'start': 577, 'end': 592, 'mesh': 'D000305'}, {'text': 'paramethasone', 'type': 'Chemical', 'start': 672, 'end': 685, 'mesh': 'D010248'}, {'text': 'corticosteroids', 'type': 'Chemical', 'start': 973, 'end': 988, 'mesh': 'D000305'}, {'text': 'paramethasone', 'type': 'Chemical', 'start': 1055, 'end': 1068, 'mesh': 'D010248'}, {'text': 'paramethasone', 'type': 'Chemical', 'start': 1149, 'end': 1162, 'mesh': 'D010248'}, {'text': 'hypersensitivity', 'type': 'Disease', 'start': 1177, 'end': 1193, 'mesh': 'D004342'}, {'text': 'allergy', 'type': 'Disease', 'start': 1387, 'end': 1394, 'mesh': 'D004342'}, {'text': 'paramethasone', 'type': 'Chemical', 'start': 1405, 'end': 1418, 'mesh': 'D010248'}]"
+338,16787750,Valproic acid induced encephalopathy--19 new cases in Germany from 1994 to 2003--a side effect associated to VPA-therapy not only in young children.,"Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously.","[{'text': 'Valproic acid', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'D014635'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 22, 'end': 36, 'mesh': 'D001927'}, {'text': 'VPA', 'type': 'Chemical', 'start': 109, 'end': 112, 'mesh': 'D014635'}, {'text': 'Valproic acid', 'type': 'Chemical', 'start': 149, 'end': 162, 'mesh': 'D014635'}, {'text': 'VPA', 'type': 'Chemical', 'start': 164, 'end': 167, 'mesh': 'D014635'}, {'text': 'pancreatitis', 'type': 'Disease', 'start': 317, 'end': 329, 'mesh': 'D010195'}, {'text': 'bone marrow suppression', 'type': 'Disease', 'start': 331, 'end': 354, 'mesh': 'D001855'}, {'text': 'VPA', 'type': 'Chemical', 'start': 356, 'end': 359, 'mesh': 'D014635'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 368, 'end': 382, 'mesh': 'D056486'}, {'text': 'VPA', 'type': 'Chemical', 'start': 387, 'end': 390, 'mesh': 'D014635'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 399, 'end': 413, 'mesh': 'D001927'}, {'text': 'VPA', 'type': 'Chemical', 'start': 436, 'end': 439, 'mesh': 'D014635'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 448, 'end': 462, 'mesh': 'D001927'}, {'text': 'impaired consciousness', 'type': 'Disease', 'start': 467, 'end': 489, 'mesh': 'D003244'}, {'text': 'seizure', 'type': 'Disease', 'start': 542, 'end': 549, 'mesh': 'D012640'}, {'text': 'hyperammonemia', 'type': 'Disease', 'start': 577, 'end': 591, 'mesh': 'D022124'}, {'text': 'VPA', 'type': 'Chemical', 'start': 640, 'end': 643, 'mesh': 'D014635'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 661, 'end': 675, 'mesh': 'D001927'}, {'text': 'VPA', 'type': 'Chemical', 'start': 764, 'end': 767, 'mesh': 'D014635'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 779, 'end': 793, 'mesh': 'D001927'}]"
+339,3173180,Haemolytic-uraemic syndrome after treatment with metronidazole.,"This paper describes the clinical features of six children who developed the haemolytic-uraemic syndrome after treatment with metronidazole. These children were older and were more likely to have undergone recent bowel surgery than are other children with this condition. While the involvement of metronidazole in the aetiology of the haemolytic-uraemic syndrome is not established firmly, the action of this drug in sensitizing tissues to oxidation injury and the reported evidence of oxidation changes in the haemolytic-uraemic syndrome suggest a possible link between metronidazole treatment and some cases of the haemolytic-uraemic syndrome.","[{'text': 'Haemolytic-uraemic syndrome', 'type': 'Disease', 'start': 0, 'end': 27, 'mesh': 'D006463'}, {'text': 'metronidazole', 'type': 'Chemical', 'start': 49, 'end': 62, 'mesh': 'D008795'}, {'text': 'haemolytic-uraemic syndrome', 'type': 'Disease', 'start': 141, 'end': 168, 'mesh': 'D006463'}, {'text': 'metronidazole', 'type': 'Chemical', 'start': 190, 'end': 203, 'mesh': 'D008795'}, {'text': 'metronidazole', 'type': 'Chemical', 'start': 361, 'end': 374, 'mesh': 'D008795'}, {'text': 'haemolytic-uraemic syndrome', 'type': 'Disease', 'start': 399, 'end': 426, 'mesh': 'D006463'}, {'text': 'haemolytic-uraemic syndrome', 'type': 'Disease', 'start': 575, 'end': 602, 'mesh': 'D006463'}, {'text': 'metronidazole', 'type': 'Chemical', 'start': 635, 'end': 648, 'mesh': 'D008795'}, {'text': 'haemolytic-uraemic syndrome', 'type': 'Disease', 'start': 681, 'end': 708, 'mesh': 'D006463'}]"
+340,8996652,Risk factors of sensorineural hearing loss in preterm infants.,"Among 547 preterm infants of < or = 34 weeks gestation born between 1987 and 1991, 8 children (1.46%) developed severe progressive and bilateral sensorineural hearing loss. Perinatal risk factors of infants with hearing loss were compared with those of two control groups matched for gestation and birth weight and for perinatal complications. Our observations demonstrated an association of hearing loss with a higher incidence of perinatal complications. Ototoxicity appeared closely related to a prolonged administration and higher total dose of ototoxic drugs, particularly aminoglycosides and furosemide. Finally, we strongly recommend to prospectively and regularly perform audiologic assessment in sick preterm children as hearing loss is of delayed onset and in most cases bilateral and severe.","[{'text': 'sensorineural hearing loss', 'type': 'Disease', 'start': 16, 'end': 42, 'mesh': 'D006319'}, {'text': 'sensorineural hearing loss', 'type': 'Disease', 'start': 208, 'end': 234, 'mesh': 'D006319'}, {'text': 'hearing loss', 'type': 'Disease', 'start': 275, 'end': 287, 'mesh': 'D034381'}, {'text': 'hearing loss', 'type': 'Disease', 'start': 455, 'end': 467, 'mesh': 'D034381'}, {'text': 'Ototoxicity', 'type': 'Disease', 'start': 520, 'end': 531, 'mesh': 'D006311'}, {'text': 'ototoxic', 'type': 'Disease', 'start': 612, 'end': 620, 'mesh': 'D006311'}, {'text': 'aminoglycosides', 'type': 'Chemical', 'start': 641, 'end': 656, 'mesh': 'D000617'}, {'text': 'furosemide', 'type': 'Chemical', 'start': 661, 'end': 671, 'mesh': 'D005665'}, {'text': 'hearing loss', 'type': 'Disease', 'start': 793, 'end': 805, 'mesh': 'D034381'}]"
+341,84204,Pharmacokinetic and clinical studies in patients with cimetidine-associated mental confusion.,"15 cases of cimetidine-associated mental confusion have been reported. In order that this syndrome might be investigated changes in mental status (M.S.) were correlated with serum concentrations and renal and hepatic function in 36 patients, 30 patients had no M.S. change on cimetidine and 6 had moderate to severe changes. These 6 patients had both renal and liver dysfunction (P less than 0.05), as well as cimetidine trough-concentrations of more than 1.25 microgram/ml (P less than 0.05). The severity of M.S. changes increased as trough-concentrations rose, 5 patients had lumbar puncture. The cerebrospinal fluid: serum ratio of cimetidine concentrations was 0.24:1 and indicates that cimetidine passes the blood-brain barrier; it also raises the possibility that M.S. changes are due to blockade of histamine H2-receptors in the central nervous system. Patients likely to have both raised trough-concentrations and mental confusion are those with both severe renal and hepatic dysfunction. They should be closely observed and should be given reduced doses of cimetidine.","[{'text': 'cimetidine', 'type': 'Chemical', 'start': 54, 'end': 64, 'mesh': 'D002927'}, {'text': 'confusion', 'type': 'Disease', 'start': 83, 'end': 92, 'mesh': 'D003221'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 106, 'end': 116, 'mesh': 'D002927'}, {'text': 'confusion', 'type': 'Disease', 'start': 135, 'end': 144, 'mesh': 'D003221'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 370, 'end': 380, 'mesh': 'D002927'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 504, 'end': 514, 'mesh': 'D002927'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 730, 'end': 740, 'mesh': 'D002927'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 786, 'end': 796, 'mesh': 'D002927'}, {'text': 'histamine', 'type': 'Chemical', 'start': 901, 'end': 910, 'mesh': 'D006632'}, {'text': 'confusion', 'type': 'Disease', 'start': 1024, 'end': 1033, 'mesh': 'D003221'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 1161, 'end': 1171, 'mesh': 'D002927'}]"
+342,9862868,Different lobular distributions of altered hepatocyte tight junctions in rat models of intrahepatic and extrahepatic cholestasis.,"Hepatocyte tight junctions (TJs), the only intercellular barrier between the sinusoidal and the canalicular spaces, play a key role in bile formation. Although hepatocyte TJs are impaired in cholestasis, attempts to localize the precise site of hepatocyte TJ damage by freeze-fracture electron microscopy have produced limited information. Recently, several TJ-associated proteins like ZO-1 and 7H6 have been identified and characterized. Immunolocalization of 7H6 appears to closely correlate with paracellular permeability. We used rat models of intrahepatic cholestasis by ethinyl estradiol (EE) treatment and extrahepatic cholestasis by bile duct ligation (BDL) to precisely determine the site of TJ damage. Alterations in hepatocyte TJs were assessed by double-immunolabeling for 7H6 and ZO-1 using a confocal laser scanning microscope. In control rats, immunostaining for 7H6 and ZO-1 colocalized to outline bile canaliculi in a continuous fashion. In contrast, 7H6 and ZO-1 immunostaining was more discontinuous, outlining the bile canaliculi after BDL. Immunostaining for 7H6, not ZO-1, decreased and predominantly appeared as discrete signals in the submembranous cytoplasm of periportal hepatocytes after BDL. After EE treatment, changes in immunostaining for 7H6 and ZO-1 were similar to those seen in periportal hepatocytes after BDL, but distributed more diffusely throughout the lobule. This study is the first to demonstrate that impairment of hepatocyte TJs occurs heterogenously in the liver lobule after BDL and suggests that BDL and EE treatments produce different lobular distributions of increased paracellular permeability.","[{'text': 'cholestasis', 'type': 'Disease', 'start': 321, 'end': 332, 'mesh': 'D002779'}, {'text': 'intrahepatic cholestasis', 'type': 'Disease', 'start': 678, 'end': 702, 'mesh': 'D002780'}, {'text': 'ethinyl estradiol', 'type': 'Chemical', 'start': 706, 'end': 723, 'mesh': 'D004997'}, {'text': 'EE', 'type': 'Chemical', 'start': 725, 'end': 727, 'mesh': 'D004997'}, {'text': 'extrahepatic cholestasis', 'type': 'Disease', 'start': 743, 'end': 767, 'mesh': 'D001651'}, {'text': 'EE', 'type': 'Chemical', 'start': 1356, 'end': 1358, 'mesh': 'D004997'}, {'text': 'EE', 'type': 'Chemical', 'start': 1682, 'end': 1684, 'mesh': 'D004997'}]"
+343,15515654,Long term audiological evaluation of beta-thalassemic patients.,"OBJECTIVE: The objective of this study was to identify the incidence and to monitor the progression of hearing loss in children and young adults with beta-thalassemia major. METHODS: One hundred and four (104) patients aged 6-35 years (mean 17,2 years) participated in the study. All patients were on a regular transfusion-chelation program maintaining a mean hemoglobin level of 9.5 gr/dl. Subjects were receiving desferrioxamine (DFO) chelation treatment with a mean daily dose of 50-60 mg/kg, 5-6 days a week during the first six years of the study, which was then reduced to 40-50 mg/kg for the following eight years. Patients were followed for 8-14 years. RESULTS: Overall, 21 out of 104 patients (20.2%) presented with high frequency sensorineural hearing loss (SNHL), either unilateral or bilateral. No ototoxic factor, other than DFO, was present in any of the patients. Patients with SNHL presented with relatively lower serum ferritin levels than those with normal hearing, however, no statistically significant difference was observed. Subjects with SNHL were submitted to DFO reduction or temporary withdrawal. Following intervention, 7 out of 21 affected patients recovered, 10 remained stable and 4 demonstrated aggravation. CONCLUSION: The findings are indicative of DFO's contributing role in the development of hearing impairment. Regular audiologic evaluation is imperative in all thalassemic patients so that early changes may be recognized and treatment may be judiciously adjusted in order to prevent or reverse hearing impairment.","[{'text': 'beta-thalassemic', 'type': 'Disease', 'start': 37, 'end': 53, 'mesh': 'D017086'}, {'text': 'hearing loss', 'type': 'Disease', 'start': 167, 'end': 179, 'mesh': 'D034381'}, {'text': 'beta-thalassemia', 'type': 'Disease', 'start': 214, 'end': 230, 'mesh': 'D017086'}, {'text': 'desferrioxamine', 'type': 'Chemical', 'start': 479, 'end': 494, 'mesh': 'D003676'}, {'text': 'DFO', 'type': 'Chemical', 'start': 496, 'end': 499, 'mesh': 'D003676'}, {'text': 'sensorineural hearing loss', 'type': 'Disease', 'start': 804, 'end': 830, 'mesh': 'D006319'}, {'text': 'SNHL', 'type': 'Disease', 'start': 832, 'end': 836, 'mesh': 'D006319'}, {'text': 'ototoxic', 'type': 'Disease', 'start': 874, 'end': 882, 'mesh': 'D006311'}, {'text': 'DFO', 'type': 'Chemical', 'start': 902, 'end': 905, 'mesh': 'D003676'}, {'text': 'SNHL', 'type': 'Disease', 'start': 957, 'end': 961, 'mesh': 'D006319'}, {'text': 'SNHL', 'type': 'Disease', 'start': 1125, 'end': 1129, 'mesh': 'D006319'}, {'text': 'DFO', 'type': 'Chemical', 'start': 1148, 'end': 1151, 'mesh': 'D003676'}, {'text': 'DFO', 'type': 'Chemical', 'start': 1346, 'end': 1349, 'mesh': 'D003676'}, {'text': 'hearing impairment', 'type': 'Disease', 'start': 1392, 'end': 1410, 'mesh': 'D034381'}, {'text': 'thalassemic', 'type': 'Disease', 'start': 1463, 'end': 1474, 'mesh': 'D013789'}, {'text': 'hearing impairment', 'type': 'Disease', 'start': 1597, 'end': 1615, 'mesh': 'D034381'}]"
+344,2024540,Design and analysis of the HYPREN-trial: safety of enalapril and prazosin in the initial treatment phase of patients with congestive heart failure.,"Since the introduction of angiotensin converting enzyme (ACE) inhibitors into the adjunctive treatment of patients with congestive heart failure, cases of severe hypotension, especially on the first day of treatment, have occasionally been reported. To assess the safety of the ACE inhibitor enalapril a multicenter, randomized, prazosin-controlled trial was designed that compared the incidence and severity of symptomatic hypotension on the first day of treatment. Trial medication was 2.5 mg enalapril or 0.5 prazosin. Subjects were 1210 inpatients with New York Heart Association (NYHA) functional class II and III. Patients who received enalapril experienced clinically and statistically significantly less symptomatic hypotension (5.2%) than the patients who received prazosin (12.9%). All patients recovered. It was concluded that treatment with enalapril was well tolerated and it is, therefore, unreasonable to restrict the initiation of treatment with enalapril to inpatients.","[{'text': 'enalapril', 'type': 'Chemical', 'start': 51, 'end': 60, 'mesh': 'D004656'}, {'text': 'prazosin', 'type': 'Chemical', 'start': 65, 'end': 73, 'mesh': 'D011224'}, {'text': 'congestive heart failure', 'type': 'Disease', 'start': 122, 'end': 146, 'mesh': 'D006333'}, {'text': 'angiotensin converting enzyme (ACE) inhibitors', 'type': 'Chemical', 'start': 174, 'end': 220, 'mesh': 'D000806'}, {'text': 'congestive heart failure', 'type': 'Disease', 'start': 268, 'end': 292, 'mesh': 'D006333'}, {'text': 'hypotension', 'type': 'Disease', 'start': 310, 'end': 321, 'mesh': 'D007022'}, {'text': 'ACE inhibitor', 'type': 'Chemical', 'start': 426, 'end': 439, 'mesh': 'D000806'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 440, 'end': 449, 'mesh': 'D004656'}, {'text': 'prazosin', 'type': 'Chemical', 'start': 477, 'end': 485, 'mesh': 'D011224'}, {'text': 'hypotension', 'type': 'Disease', 'start': 572, 'end': 583, 'mesh': 'D007022'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 643, 'end': 652, 'mesh': 'D004656'}, {'text': 'prazosin', 'type': 'Chemical', 'start': 660, 'end': 668, 'mesh': 'D011224'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 790, 'end': 799, 'mesh': 'D004656'}, {'text': 'hypotension', 'type': 'Disease', 'start': 872, 'end': 883, 'mesh': 'D007022'}, {'text': 'prazosin', 'type': 'Chemical', 'start': 922, 'end': 930, 'mesh': 'D011224'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 1001, 'end': 1010, 'mesh': 'D004656'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 1110, 'end': 1119, 'mesh': 'D004656'}]"
+345,12090760,Antagonism between interleukin 3 and erythropoietin in mice with azidothymidine-induced anemia and in bone marrow endothelial cells.,"Azidothymidine (AZT)-induced anemia in mice can be reversed by the administration of IGF-IL-3 (fusion protein of insulin-like growth factor II (IGF II) and interleukin 3). Although interleukin 3 (IL-3) and erythropoietin (EPO) are known to act synergistically on hematopoietic cell proliferation in vitro, injection of IGF-IL-3 and EPO in AZT-treated mice resulted in a reduction of red cells and an increase of plasma EPO levels as compared to animals treated with IGF-IL-3 or EPO alone. We tested the hypothesis that the antagonistic effect of IL-3 and EPO on erythroid cells may be mediated by endothelial cells. Bovine liver erythroid cells were cultured on monolayers of human bone marrow endothelial cells previously treated with EPO and IGF-IL-3. There was a significant reduction of thymidine incorporation into both erythroid and endothelial cells in cultures pre-treated with IGF-IL-3 and EPO. Endothelial cell culture supernatants separated by ultrafiltration and ultracentrifugation from cells treated with EPO and IL-3 significantly reduced thymidine incorporation into erythroid cells as compared to identical fractions obtained from the media of cells cultured with EPO alone. These results suggest that endothelial cells treated simultaneously with EPO and IL-3 have a negative effect on erythroid cell production.","[{'text': 'azidothymidine', 'type': 'Chemical', 'start': 65, 'end': 79, 'mesh': 'D015215'}, {'text': 'anemia', 'type': 'Disease', 'start': 88, 'end': 94, 'mesh': 'D000740'}, {'text': 'Azidothymidine', 'type': 'Chemical', 'start': 133, 'end': 147, 'mesh': 'D015215'}, {'text': 'AZT', 'type': 'Chemical', 'start': 149, 'end': 152, 'mesh': 'D015215'}, {'text': 'anemia', 'type': 'Disease', 'start': 162, 'end': 168, 'mesh': 'D000740'}, {'text': 'AZT', 'type': 'Chemical', 'start': 472, 'end': 475, 'mesh': 'D015215'}, {'text': 'thymidine', 'type': 'Chemical', 'start': 924, 'end': 933, 'mesh': 'D013936'}, {'text': 'thymidine', 'type': 'Chemical', 'start': 1187, 'end': 1196, 'mesh': 'D013936'}]"
+346,7516729,Interactive effects of variations in [Na]o and [Ca]o on rat atrial spontaneous frequency.,"The effects of varying the extracellular concentrations of Na and Ca ([Na]o and [Ca]o) on both, the spontaneous beating and the negative chronotropic action of verapamil, were studied in the isolated rat atria. Basal frequency (BF) evaluated by surface electrogram was 223 +/- 4 beats/min. in control Krebs-Ringer containing 137 mM Na and 1.35 mM Ca (N). It decreased by 16 +/- 3% by lowering [Na]o to 78 mM (LNa), 23 +/- 2% by lowering simultaneously [Na]o to 78 mM and [Ca]o to 0.675 mM (LNa+LCa) and 31 +/- 5% by lowering [Na]o to 78 mM plus increasing [Ca]o to 3.6 mM (LNa+HCa). At normal [Na]o, decrease (0.675 mM) or increase (3.6 mM) of [Ca]o did not modify BF; a reduction of ten times (0.135 mM of normal [Ca]o was effective to reduce BF by 40 +/- 13%. All negative chronotropic effects were BF-dependent. Dose-dependent bradycardia induced by verapamil was potentiated by LNa, LCa, and HCa. Independent but not additive effects of Na and Ca are shown by decreases in the values of [verapamil]o needed to reduce BF by 30% (IC30) with the following order of inhibitory potency: LNa > LCa > HCa > N, resulting LNa+HCa similar to LNa. The [verapamil]o that arrested atrial beating (AC) was also potentiated with the order LNa = LNa+LCa = LNa+HCa = LCa > HCa = N. The results indicate that rat atrial spontaneous beating is more dependent on [Na]o than on [Ca]o in a range of +/- 50% of their normal concentration. Also the enhancement of verapamil effects on atrial beating was more pronounced at LNa than at LCa.(ABSTRACT TRUNCATED AT 250 WORDS)","[{'text': 'Na', 'type': 'Chemical', 'start': 38, 'end': 40, 'mesh': 'D012964'}, {'text': 'Ca', 'type': 'Chemical', 'start': 48, 'end': 50, 'mesh': 'D002118'}, {'text': 'Na', 'type': 'Chemical', 'start': 149, 'end': 151, 'mesh': 'D012964'}, {'text': 'Ca', 'type': 'Chemical', 'start': 156, 'end': 158, 'mesh': 'D002118'}, {'text': 'Na', 'type': 'Chemical', 'start': 161, 'end': 163, 'mesh': 'D012964'}, {'text': 'Ca', 'type': 'Chemical', 'start': 171, 'end': 173, 'mesh': 'D002118'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 250, 'end': 259, 'mesh': 'D014700'}, {'text': 'Na', 'type': 'Chemical', 'start': 422, 'end': 424, 'mesh': 'D012964'}, {'text': 'Ca', 'type': 'Chemical', 'start': 437, 'end': 439, 'mesh': 'D002118'}, {'text': 'Na', 'type': 'Chemical', 'start': 484, 'end': 486, 'mesh': 'D012964'}, {'text': 'Na', 'type': 'Chemical', 'start': 543, 'end': 545, 'mesh': 'D012964'}, {'text': 'Ca', 'type': 'Chemical', 'start': 562, 'end': 564, 'mesh': 'D002118'}, {'text': 'Na', 'type': 'Chemical', 'start': 616, 'end': 618, 'mesh': 'D012964'}, {'text': 'Ca', 'type': 'Chemical', 'start': 647, 'end': 649, 'mesh': 'D002118'}, {'text': 'Na', 'type': 'Chemical', 'start': 684, 'end': 686, 'mesh': 'D012964'}, {'text': 'Ca', 'type': 'Chemical', 'start': 735, 'end': 737, 'mesh': 'D002118'}, {'text': 'Ca', 'type': 'Chemical', 'start': 805, 'end': 807, 'mesh': 'D002118'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 920, 'end': 931, 'mesh': 'D001919'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 943, 'end': 952, 'mesh': 'D014700'}, {'text': 'Na', 'type': 'Chemical', 'start': 1031, 'end': 1033, 'mesh': 'D012964'}, {'text': 'Ca', 'type': 'Chemical', 'start': 1038, 'end': 1040, 'mesh': 'D002118'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 1082, 'end': 1091, 'mesh': 'D014700'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 1236, 'end': 1245, 'mesh': 'D014700'}, {'text': 'Na', 'type': 'Chemical', 'start': 1438, 'end': 1440, 'mesh': 'D012964'}, {'text': 'Ca', 'type': 'Chemical', 'start': 1452, 'end': 1454, 'mesh': 'D002118'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 1534, 'end': 1543, 'mesh': 'D014700'}]"
+347,2802551,Sodium status influences chronic amphotericin B nephrotoxicity in rats.,"The nephrotoxic potential of amphotericin B (5 mg/kg per day intraperitoneally for 3 weeks) has been investigated in salt-depleted, normal-salt, and salt-loaded rats. In salt-depleted rats, amphotericin B decreased creatinine clearance linearly with time, with an 85% reduction by week 3. In contrast, in normal-salt rats creatinine clearance was decreased but to a lesser extent at week 2 and 3, and in salt-loaded rats creatinine clearance did not change for 2 weeks and was decreased by 43% at week 3. All rats in the sodium-depleted group had histopathological evidence of patchy tubular cytoplasmic degeneration in tubules that was not observed in any normal-salt or salt-loaded rat. Concentrations of amphotericin B in plasma were not significantly different among the three groups at any time during the study. However, at the end of 3 weeks, amphotericin B levels in the kidneys and liver were significantly higher in salt-depleted and normal-salt rats than those in salt-loaded rats, with plasma/kidney ratios of 21, 14, and 8 in salt-depleted, normal-salt, and salt-loaded rats, respectively. In conclusion, reductions in creatinine clearance and renal amphotericin B accumulation after chronic amphotericin B administration were enhanced by salt depletion and attenuated by sodium loading in rats.","[{'text': 'Sodium', 'type': 'Chemical', 'start': 0, 'end': 6, 'mesh': 'D012964'}, {'text': 'amphotericin B', 'type': 'Chemical', 'start': 33, 'end': 47, 'mesh': 'D000666'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 48, 'end': 62, 'mesh': 'D007674'}, {'text': 'nephrotoxic', 'type': 'Disease', 'start': 76, 'end': 87, 'mesh': 'D007674'}, {'text': 'amphotericin B', 'type': 'Chemical', 'start': 101, 'end': 115, 'mesh': 'D000666'}, {'text': 'amphotericin B', 'type': 'Chemical', 'start': 262, 'end': 276, 'mesh': 'D000666'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 287, 'end': 297, 'mesh': 'D003404'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 394, 'end': 404, 'mesh': 'D003404'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 493, 'end': 503, 'mesh': 'D003404'}, {'text': 'sodium', 'type': 'Chemical', 'start': 593, 'end': 599, 'mesh': 'D012964'}, {'text': 'amphotericin B', 'type': 'Chemical', 'start': 779, 'end': 793, 'mesh': 'D000666'}, {'text': 'amphotericin B', 'type': 'Chemical', 'start': 922, 'end': 936, 'mesh': 'D000666'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1204, 'end': 1214, 'mesh': 'D003404'}, {'text': 'amphotericin B', 'type': 'Chemical', 'start': 1235, 'end': 1249, 'mesh': 'D000666'}, {'text': 'amphotericin B', 'type': 'Chemical', 'start': 1277, 'end': 1291, 'mesh': 'D000666'}, {'text': 'sodium', 'type': 'Chemical', 'start': 1357, 'end': 1363, 'mesh': 'D012964'}]"
+348,19346865,Reversible inferior colliculus lesion in metronidazole-induced encephalopathy: magnetic resonance findings on diffusion-weighted and fluid attenuated inversion recovery imaging.,"OBJECTIVE: This is to present reversible inferior colliculus lesions in metronidazole-induced encephalopathy, to focus on the diffusion-weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) imaging. MATERIALS AND METHODS: From November 2005 to September 2007, 8 patients (5 men and 3 women) were diagnosed as having metronidazole-induced encephalopathy (age range; 43-78 years). They had been taking metronidazole (total dosage, 45-120 g; duration, 30 days to 2 months) to treat the infection in various organs. Initial brain magnetic resonance imaging (MRI) were obtained after the hospitalization, including DWI (8/8), apparent diffusion coefficient (ADC) map (4/8), FLAIR (7/8), and T2-weighted image (8/8). Follow-up MRIs were performed on 5 patients from third to 14th days after discontinuation of metronidazole administration. Findings of initial and follow-up MRIs were retrospectively evaluated by 2 neuroradiologists by consensus, to analyze the presence of abnormal signal intensities, their locations, and signal changes on follow-up images. RESULTS: Initial MRIs showed abnormal high signal intensities on DWI and FLAIR (or T2-weighted image) at the dentate nucleus (8/8), inferior colliculus (6/8), corpus callosum (2/8), pons (2/8), medulla (1/8), and bilateral cerebral white matter (1/8). High-signal intensity lesions on DWI tended to show low signal intensity on ADC map (3/4), but in one patient, high signal intensity was shown at bilateral dentate nuclei on not only DWI but also ADC map. All the lesions in dentate, inferior colliculus, pons, and medullas had been resolved completely on follow-up MRIs in 5 patients, but in 1 patient of them, corpus callosal lesion persisted. CONCLUSIONS: Reversible inferior colliculus lesions could be considered as the characteristic for metronidazole-induced encephalopathy, next to the dentate nucleus involvement.","[{'text': 'inferior colliculus lesion', 'type': 'Disease', 'start': 11, 'end': 37, 'mesh': 'D001927'}, {'text': 'metronidazole', 'type': 'Chemical', 'start': 41, 'end': 54, 'mesh': 'D008795'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 63, 'end': 77, 'mesh': 'D001927'}, {'text': 'inferior colliculus lesions', 'type': 'Disease', 'start': 219, 'end': 246, 'mesh': 'D001927'}, {'text': 'metronidazole', 'type': 'Chemical', 'start': 250, 'end': 263, 'mesh': 'D008795'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 272, 'end': 286, 'mesh': 'D001927'}, {'text': 'metronidazole', 'type': 'Chemical', 'start': 511, 'end': 524, 'mesh': 'D008795'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 533, 'end': 547, 'mesh': 'D001927'}, {'text': 'metronidazole', 'type': 'Chemical', 'start': 595, 'end': 608, 'mesh': 'D008795'}, {'text': 'infection', 'type': 'Disease', 'start': 678, 'end': 687, 'mesh': 'D007239'}, {'text': 'metronidazole', 'type': 'Chemical', 'start': 999, 'end': 1012, 'mesh': 'D008795'}, {'text': 'callosal lesion', 'type': 'Disease', 'start': 1869, 'end': 1884, 'mesh': 'D001927'}, {'text': 'inferior colliculus lesions', 'type': 'Disease', 'start': 1920, 'end': 1947, 'mesh': 'D001927'}, {'text': 'metronidazole', 'type': 'Chemical', 'start': 1994, 'end': 2007, 'mesh': 'D008795'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 2016, 'end': 2030, 'mesh': 'D001927'}]"
+349,2334618,Comparison of the respiratory effects of i.v. infusions of morphine and regional analgesia by extradural block.,"The incidence of postoperative respiratory apnoea was compared between five patients receiving a continuous i.v. infusion of morphine (mean 73.6 mg) and five patients receiving a continuous extradural infusion of 0.25% bupivacaine (mean 192 mg) in the 24-h period following upper abdominal surgery. Monitoring consisted of airflow detection by a carbon dioxide analyser, chest wall movement detected by pneumatic capsules, and continuous electrocardiograph recorded with a Holter ambulatory monitor. Both obstructive (P less than 0.05) and central apnoea (P less than 0.05) occurred more frequently in patients who had a morphine infusion. There was also a higher incidence of tachyarrhythmias (P less than 0.05) and ventricular ectopic beats (P less than 0.05) in the morphine infusion group.","[{'text': 'morphine', 'type': 'Chemical', 'start': 59, 'end': 67, 'mesh': 'D009020'}, {'text': 'apnoea', 'type': 'Disease', 'start': 155, 'end': 161, 'mesh': 'D001049'}, {'text': 'morphine', 'type': 'Chemical', 'start': 237, 'end': 245, 'mesh': 'D009020'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 331, 'end': 342, 'mesh': 'D002045'}, {'text': 'carbon dioxide', 'type': 'Chemical', 'start': 458, 'end': 472, 'mesh': 'D002245'}, {'text': 'morphine', 'type': 'Chemical', 'start': 733, 'end': 741, 'mesh': 'D009020'}, {'text': 'tachyarrhythmias', 'type': 'Disease', 'start': 789, 'end': 805, 'mesh': 'D013610'}, {'text': 'ventricular ectopic beats', 'type': 'Disease', 'start': 829, 'end': 854, 'mesh': 'D018879'}, {'text': 'morphine', 'type': 'Chemical', 'start': 881, 'end': 889, 'mesh': 'D009020'}]"
+350,8864707,Magnetic resonance volumetry of the cerebellum in epileptic patients after phenytoin overdosages.,"The aim of this study was to evaluate the relationship between phenytoin medication and cerebellar atrophy in patients who had experienced clinical intoxication. Five females and 6 males, 21-59 years of age, were examined with a 1.5-T whole-body system using a circular polarized head coil. Conventional spin echo images were acquired in the sagittal and transverse orientation. In addition, we performed a high-resolution 3D gradient echo, T1-weighted sequences at a 1-mm slice thickness. The images were subsequently processed to obtain volumetric data for the cerebellum. Cerebellar volume for the patient group ranged between 67.66 and 131.08 ml (mean 108.9 ml). In addition 3D gradient echo data sets from 10 healthy male and 10 healthy female age-matched volunteers were used to compare cerebellar volumes. Using linear regression we found that no correlation exists between seizure duration, elevation of phenytoin serum levels and cerebellar volume. However, multiple regression for the daily dosage, duration of phenytoin treatment and cerebellar volume revealed a correlation of these parameters. We conclude that phenytoin overdosage does not necessarily result in cerebellar atrophy and it is unlikely that phenytoin medication was the only cause of cerebellar atrophy in the remaining patients. Quantitative morphometric studies of the cerebellum provide valuable insights into the pathogenesis of cerebellar disorders.","[{'text': 'epileptic', 'type': 'Disease', 'start': 50, 'end': 59, 'mesh': 'D004827'}, {'text': 'phenytoin', 'type': 'Chemical', 'start': 75, 'end': 84, 'mesh': 'D010672'}, {'text': 'overdosages', 'type': 'Disease', 'start': 85, 'end': 96, 'mesh': 'D062787'}, {'text': 'phenytoin', 'type': 'Chemical', 'start': 161, 'end': 170, 'mesh': 'D010672'}, {'text': 'cerebellar atrophy', 'type': 'Disease', 'start': 186, 'end': 204, 'mesh': 'D002526'}, {'text': 'seizure', 'type': 'Disease', 'start': 979, 'end': 986, 'mesh': 'D012640'}, {'text': 'phenytoin', 'type': 'Chemical', 'start': 1010, 'end': 1019, 'mesh': 'D010672'}, {'text': 'phenytoin', 'type': 'Chemical', 'start': 1119, 'end': 1128, 'mesh': 'D010672'}, {'text': 'phenytoin', 'type': 'Chemical', 'start': 1222, 'end': 1231, 'mesh': 'D010672'}, {'text': 'overdosage', 'type': 'Disease', 'start': 1232, 'end': 1242, 'mesh': 'D062787'}, {'text': 'cerebellar atrophy', 'type': 'Disease', 'start': 1274, 'end': 1292, 'mesh': 'D002526'}, {'text': 'phenytoin', 'type': 'Chemical', 'start': 1317, 'end': 1326, 'mesh': 'D010672'}, {'text': 'cerebellar atrophy', 'type': 'Disease', 'start': 1360, 'end': 1378, 'mesh': 'D002526'}, {'text': 'cerebellar disorders', 'type': 'Disease', 'start': 1509, 'end': 1529, 'mesh': 'D002526'}]"
+351,12589964,"Evaluation of cardiac troponin I and T levels as markers of myocardial damage in doxorubicin-induced cardiomyopathy rats, and their relationship with echocardiographic and histological findings.","BACKGROUND: Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. We investigated the diagnostic value of cTnI and cTnT for the diagnosis of myocardial damage in a rat model of doxorubicin (DOX)-induced cardiomyopathy, and we examined the relationship between serial cTnI and cTnT with the development of cardiac disorders monitored by echocardiography and histological examinations in this model. METHODS: Thirty-five Wistar rats were given 1.5 mg/kg DOX, i.v., weekly for up to 8 weeks for a total cumulative dose of 12 mg/kg BW. Ten rats received saline as a control group. cTnI was measured with Access(R) (ng/ml) and a research immunoassay (pg/ml), and compared with cTnT, CK-MB mass and CK. By using transthoracic echocardiography, anterior and posterior wall thickness, LV diameters and LV fractional shortening (FS) were measured in all rats before DOX or saline, and at weeks 6 and 9 after treatment in all surviving rats. Histology was performed in DOX-rats at 6 and 9 weeks after the last DOX dose and in all controls. RESULTS: Eighteen of the DOX rats died prematurely of general toxicity during the 9-week period. End-diastolic (ED) and end-systolic (ES) LV diameters/BW significantly increased, whereas LV FS was decreased after 9 weeks in the DOX group (p<0.001). These parameters remained unchanged in controls. Histological evaluation of hearts from all rats given DOX revealed significant slight degrees of perivascular and interstitial fibrosis. In 7 of the 18 rats, degeneration and myocyte vacuolisation were found. Only five of the controls exhibited evidence of very slight perivascular fibrosis. A significant rise in cTnT was found in DOX rats after cumulative doses of 7.5 and 12 mg/kg in comparison with baseline (p<0.05). cTnT found in rats after 12 mg/kg were significantly greater than that found after 7.5 mg/kg DOX. Maximal cTnI (pg/ml) and cTnT levels were significantly increased in DOX rats compared with controls (p=0.006, 0.007). cTnI (ng/ml), CK-MB mass and CK remained unchanged in DOX rats compared with controls. All markers remained stable in controls. Analysis of data revealed a significant correlation between maximal cTnT and ED and ES LV diameters/BW (r=0.81 and 0.65; p<0.0001). A significant relationship was observed between maximal cTnT and the extent of myocardial morphological changes, and between LV diameters/BW and histological findings. CONCLUSIONS: Among markers of ischemic injury after DOX in rats, cTnT showed the greatest ability to detect myocardial damage assessed by echocardiographic detection and histological changes. Although there was a discrepancy between the amount of cTnI and cTnT after DOX, probably due to heterogeneity in cross-reactivities of mAbs to various cTnI and cTnT forms, it is likely that cTnT in rats after DOX indicates cell damage determined by the magnitude of injury induced and that cTnT should be a useful marker for the prediction of experimentally induced cardiotoxicity and possibly for cardioprotective experiments.","[{'text': 'myocardial damage', 'type': 'Disease', 'start': 60, 'end': 77, 'mesh': 'D009202'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 81, 'end': 92, 'mesh': 'D004317'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 101, 'end': 115, 'mesh': 'D009202'}, {'text': 'myocardial cell injury', 'type': 'Disease', 'start': 310, 'end': 332, 'mesh': 'D009202'}, {'text': 'myocardial damage', 'type': 'Disease', 'start': 409, 'end': 426, 'mesh': 'D009202'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 445, 'end': 456, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 458, 'end': 461, 'mesh': 'D004317'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 471, 'end': 485, 'mesh': 'D009202'}, {'text': 'cardiac disorders', 'type': 'Disease', 'start': 573, 'end': 590, 'mesh': 'D006331'}, {'text': 'DOX', 'type': 'Chemical', 'start': 720, 'end': 723, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1125, 'end': 1128, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1227, 'end': 1230, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1268, 'end': 1271, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1323, 'end': 1326, 'mesh': 'D004317'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1360, 'end': 1368, 'mesh': 'D064420'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1526, 'end': 1529, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1650, 'end': 1653, 'mesh': 'D004317'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 1723, 'end': 1731, 'mesh': 'D005355'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 1878, 'end': 1886, 'mesh': 'D005355'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1928, 'end': 1931, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 2111, 'end': 2114, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 2185, 'end': 2188, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 2289, 'end': 2292, 'mesh': 'D004317'}, {'text': 'ischemic injury', 'type': 'Disease', 'start': 2693, 'end': 2708, 'mesh': 'D017202'}, {'text': 'DOX', 'type': 'Chemical', 'start': 2715, 'end': 2718, 'mesh': 'D004317'}, {'text': 'myocardial damage', 'type': 'Disease', 'start': 2771, 'end': 2788, 'mesh': 'D009202'}, {'text': 'DOX', 'type': 'Chemical', 'start': 2930, 'end': 2933, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 3064, 'end': 3067, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 3221, 'end': 3235, 'mesh': 'D066126'}]"
+352,11263551,Calcineurin-inhibitor induced pain syndrome (CIPS): a severe disabling complication after organ transplantation.,"Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS.","[{'text': 'pain', 'type': 'Disease', 'start': 30, 'end': 34, 'mesh': 'D010146'}, {'text': 'CIPS', 'type': 'Disease', 'start': 45, 'end': 49, 'mesh': '-1'}, {'text': 'pain', 'type': 'Disease', 'start': 118, 'end': 122, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 272, 'end': 276, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 304, 'end': 308, 'mesh': 'D010146'}, {'text': 'Pain', 'type': 'Disease', 'start': 532, 'end': 536, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 586, 'end': 590, 'mesh': 'D010146'}, {'text': 'reflex sympathetic dystrophy', 'type': 'Disease', 'start': 597, 'end': 625, 'mesh': 'D012019'}, {'text': 'polyneuropathy', 'type': 'Disease', 'start': 627, 'end': 641, 'mesh': 'D011115'}, {'text': ""Morton's neuralgia"", 'type': 'Disease', 'start': 643, 'end': 661, 'mesh': 'D009437'}, {'text': 'gout', 'type': 'Disease', 'start': 663, 'end': 667, 'mesh': 'D006073'}, {'text': 'osteoporosis', 'type': 'Disease', 'start': 669, 'end': 681, 'mesh': 'D010024'}, {'text': 'avascular necrosis', 'type': 'Disease', 'start': 683, 'end': 701, 'mesh': 'D010020'}, {'text': 'intermittent claudication', 'type': 'Disease', 'start': 703, 'end': 728, 'mesh': 'D007383'}, {'text': 'foot deformities', 'type': 'Disease', 'start': 742, 'end': 758, 'mesh': 'D005530'}, {'text': 'stress fractures', 'type': 'Disease', 'start': 760, 'end': 776, 'mesh': 'D015775'}, {'text': 'hyperparathyroidism', 'type': 'Disease', 'start': 782, 'end': 801, 'mesh': 'D006961'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 820, 'end': 832, 'mesh': 'D016572'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 837, 'end': 847, 'mesh': 'D016559'}, {'text': 'calcium', 'type': 'Chemical', 'start': 888, 'end': 895, 'mesh': 'D002118'}, {'text': 'pain', 'type': 'Disease', 'start': 930, 'end': 934, 'mesh': 'D010146'}, {'text': 'Pain', 'type': 'Disease', 'start': 970, 'end': 974, 'mesh': 'D010146'}, {'text': 'CIPS', 'type': 'Disease', 'start': 985, 'end': 989, 'mesh': '-1'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 1027, 'end': 1039, 'mesh': 'D016572'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 1043, 'end': 1053, 'mesh': 'D016559'}, {'text': 'CIPS', 'type': 'Disease', 'start': 1270, 'end': 1274, 'mesh': '-1'}]"
+353,10520387,The haemodynamic effects of propofol in combination with ephedrine in elderly patients (ASA groups 3 and 4).,"The marked vasodilator and negative inotropic effects of propofol are disadvantages in frail elderly patients. We investigated the safety and efficacy of adding different doses of ephedrine to propofol in order to obtund the hypotensive response. The haemodynamic effects of adding 15, 20 or 25 mg of ephedrine to 200 mg of propofol were compared to control in 40 ASA 3/4 patients over 60 years presenting for genito-urinary surgery. The addition of ephedrine to propofol appears to be an effective method of obtunding the hypotensive response to propofol at all doses used in this study. However, marked tachycardia associated with the use of ephedrine in combination with propofol occurred in the majority of patients, occasionally reaching high levels in individual patients. Due to the risk of this tachycardia inducing myocardial ischemia, we would not recommend the use in elderly patients of any of the ephedrine/propofol/mixtures studied.","[{'text': 'propofol', 'type': 'Chemical', 'start': 28, 'end': 36, 'mesh': 'D015742'}, {'text': 'ephedrine', 'type': 'Chemical', 'start': 57, 'end': 66, 'mesh': 'D004809'}, {'text': 'propofol', 'type': 'Chemical', 'start': 166, 'end': 174, 'mesh': 'D015742'}, {'text': 'ephedrine', 'type': 'Chemical', 'start': 289, 'end': 298, 'mesh': 'D004809'}, {'text': 'propofol', 'type': 'Chemical', 'start': 302, 'end': 310, 'mesh': 'D015742'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 334, 'end': 345, 'mesh': 'D007022'}, {'text': 'ephedrine', 'type': 'Chemical', 'start': 410, 'end': 419, 'mesh': 'D004809'}, {'text': 'propofol', 'type': 'Chemical', 'start': 433, 'end': 441, 'mesh': 'D015742'}, {'text': 'ephedrine', 'type': 'Chemical', 'start': 559, 'end': 568, 'mesh': 'D004809'}, {'text': 'propofol', 'type': 'Chemical', 'start': 572, 'end': 580, 'mesh': 'D015742'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 632, 'end': 643, 'mesh': 'D007022'}, {'text': 'propofol', 'type': 'Chemical', 'start': 656, 'end': 664, 'mesh': 'D015742'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 714, 'end': 725, 'mesh': 'D013610'}, {'text': 'ephedrine', 'type': 'Chemical', 'start': 753, 'end': 762, 'mesh': 'D004809'}, {'text': 'propofol', 'type': 'Chemical', 'start': 783, 'end': 791, 'mesh': 'D015742'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 912, 'end': 923, 'mesh': 'D013610'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 933, 'end': 952, 'mesh': 'D017202'}, {'text': 'ephedrine', 'type': 'Chemical', 'start': 1019, 'end': 1028, 'mesh': 'D004809'}, {'text': 'propofol', 'type': 'Chemical', 'start': 1029, 'end': 1037, 'mesh': 'D015742'}]"
+354,230316,Neurotoxicity of halogenated hydroxyquinolines: clinical analysis of cases reported outside Japan.,"An analysis is presented of 220 cases of possible neurotoxic reactions to halogenated hydroxyquinolines reported from outside Japan. In 80 cases insufficient information was available for adequate comment and in 29 a relationship to the administration of clioquinol could be excluded. Of the remainder, a relationship to clioquinol was considered probable in 42 and possible in 69 cases. In six of the probable cases the neurological disturbance consisted of an acute reversible encephalopathy usually related to the ingestion of a high dose of clioquinol over a short period. The most common manifestation, observed in 15 further cases, was isolated optic atrophy. This was most frequently found in children, many of whom had received clioquinol as treatment for acrodermatitis enteropathica. In the remaining cases, a combination of myelopathy, visual disturbance, and peripheral neuropathy was the most common manifestation. Isolated myelopathy or peripheral neuropathy, or these manifestations occurring together, were infrequent. The onset of all manifestations (except toxic encephalopathy) was usually subacute, with subsequent partial recovery. Older subjects tended to display more side effects. The full syndrome of subacute myelo-optic neuropathy was more frequent in women, but they tended to have taken greater quantities of the drug.","[{'text': 'Neurotoxicity', 'type': 'Disease', 'start': 0, 'end': 13, 'mesh': 'D020258'}, {'text': 'halogenated hydroxyquinolines', 'type': 'Chemical', 'start': 17, 'end': 46, 'mesh': 'D006912'}, {'text': 'neurotoxic', 'type': 'Disease', 'start': 149, 'end': 159, 'mesh': 'D020258'}, {'text': 'halogenated hydroxyquinolines', 'type': 'Chemical', 'start': 173, 'end': 202, 'mesh': 'D006912'}, {'text': 'clioquinol', 'type': 'Chemical', 'start': 354, 'end': 364, 'mesh': 'D007464'}, {'text': 'clioquinol', 'type': 'Chemical', 'start': 420, 'end': 430, 'mesh': 'D007464'}, {'text': 'neurological disturbance', 'type': 'Disease', 'start': 520, 'end': 544, 'mesh': 'D009422'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 578, 'end': 592, 'mesh': 'D001927'}, {'text': 'clioquinol', 'type': 'Chemical', 'start': 644, 'end': 654, 'mesh': 'D007464'}, {'text': 'optic atrophy', 'type': 'Disease', 'start': 750, 'end': 763, 'mesh': 'D009896'}, {'text': 'clioquinol', 'type': 'Chemical', 'start': 835, 'end': 845, 'mesh': 'D007464'}, {'text': 'acrodermatitis enteropathica', 'type': 'Disease', 'start': 863, 'end': 891, 'mesh': 'C538178'}, {'text': 'myelopathy', 'type': 'Disease', 'start': 934, 'end': 944, 'mesh': 'D013118'}, {'text': 'visual disturbance', 'type': 'Disease', 'start': 946, 'end': 964, 'mesh': 'D014786'}, {'text': 'peripheral neuropathy', 'type': 'Disease', 'start': 970, 'end': 991, 'mesh': 'D010523'}, {'text': 'myelopathy', 'type': 'Disease', 'start': 1036, 'end': 1046, 'mesh': 'D013118'}, {'text': 'peripheral neuropathy', 'type': 'Disease', 'start': 1050, 'end': 1071, 'mesh': 'D010523'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 1180, 'end': 1194, 'mesh': 'D001927'}]"
+355,11807648,Epileptic seizures following cortical application of fibrin sealants containing tranexamic acid in rats.,"BACKGROUND: Fibrin sealants (FS) derived from human plasma are frequently used in neurosurgery. In order to increase clot stability, FS typically contain aprotinin, a natural fibrinolysis inhibitor. Recently, synthetic fibrinolysis inhibitors such as tranexamic acid (tAMCA) have been considered as substitutes for aprotinin. However, tAMCA has been shown to cause epileptic seizures. We wanted to study whether tAMCA retains its convulsive action if incorporated into a FS. METHOD: FS containing aprotinin or different concentrations of tAMCA (0.5-47.5 mg/ml) were applied to the pial surface of the cortex of anaesthetized rats. The response of the animals was evaluated using electroencephalography and by monitoring the clinical behaviour during and after recovery from anaesthesia. FINDINGS: FS containing tAMCA caused paroxysmal brain activity which was associated with distinct convulsive behaviours. The degree of these seizures increased with increasing concentration of tAMCA. Thus, FS containing 47.5 mg/ml tAMCA evoked generalized seizures in all tested rats (n=6) while the lowest concentration of tAMCA (0.5 mg/ml) only evoked brief episodes of jerk-correlated convulsive potentials in 1 of 6 rats. In contrast, FS containing aprotinin did not evoke any paroxysmal activity. INTERPRETATION: Tranexamic acid retains its convulsive action within FS. Thus, use of FS containing tAMCA for surgery within or close to the CNS may pose a substantial risk to the patient.","[{'text': 'Epileptic seizures', 'type': 'Disease', 'start': 0, 'end': 18, 'mesh': 'D004827'}, {'text': 'tranexamic acid', 'type': 'Chemical', 'start': 80, 'end': 95, 'mesh': 'D014148'}, {'text': 'tranexamic acid', 'type': 'Chemical', 'start': 356, 'end': 371, 'mesh': 'D014148'}, {'text': 'tAMCA', 'type': 'Chemical', 'start': 373, 'end': 378, 'mesh': 'D014148'}, {'text': 'tAMCA', 'type': 'Chemical', 'start': 440, 'end': 445, 'mesh': 'D014148'}, {'text': 'epileptic seizures', 'type': 'Disease', 'start': 470, 'end': 488, 'mesh': 'D004827'}, {'text': 'tAMCA', 'type': 'Chemical', 'start': 517, 'end': 522, 'mesh': 'D014148'}, {'text': 'convulsive', 'type': 'Disease', 'start': 535, 'end': 545, 'mesh': 'D012640'}, {'text': 'tAMCA', 'type': 'Chemical', 'start': 643, 'end': 648, 'mesh': 'D014148'}, {'text': 'tAMCA', 'type': 'Chemical', 'start': 916, 'end': 921, 'mesh': 'D014148'}, {'text': 'convulsive', 'type': 'Disease', 'start': 990, 'end': 1000, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 1033, 'end': 1041, 'mesh': 'D012640'}, {'text': 'tAMCA', 'type': 'Chemical', 'start': 1085, 'end': 1090, 'mesh': 'D014148'}, {'text': 'tAMCA', 'type': 'Chemical', 'start': 1123, 'end': 1128, 'mesh': 'D014148'}, {'text': 'generalized seizures', 'type': 'Disease', 'start': 1136, 'end': 1156, 'mesh': 'D012640'}, {'text': 'tAMCA', 'type': 'Chemical', 'start': 1216, 'end': 1221, 'mesh': 'D014148'}, {'text': 'convulsive', 'type': 'Disease', 'start': 1280, 'end': 1290, 'mesh': 'D012640'}, {'text': 'Tranexamic acid', 'type': 'Chemical', 'start': 1410, 'end': 1425, 'mesh': 'D014148'}, {'text': 'convulsive', 'type': 'Disease', 'start': 1438, 'end': 1448, 'mesh': 'D012640'}, {'text': 'tAMCA', 'type': 'Chemical', 'start': 1494, 'end': 1499, 'mesh': 'D014148'}]"
+356,14596845,A diet promoting sugar dependency causes behavioral cross-sensitization to a low dose of amphetamine.,"Previous research in this laboratory has shown that a diet of intermittent excessive sugar consumption produces a state with neurochemical and behavioral similarities to drug dependency. The present study examined whether female rats on various regimens of sugar access would show behavioral cross-sensitization to a low dose of amphetamine. After a 30-min baseline measure of locomotor activity (day 0), animals were maintained on a cyclic diet of 12-h deprivation followed by 12-h access to 10% sucrose solution and chow pellets (12 h access starting 4 h after onset of the dark period) for 21 days. Locomotor activity was measured again for 30 min at the beginning of days 1 and 21 of sugar access. Beginning on day 22, all rats were maintained on ad libitum chow. Nine days later locomotor activity was measured in response to a single low dose of amphetamine (0.5 mg/kg). The animals that had experienced cyclic sucrose and chow were hyperactive in response to amphetamine compared with four control groups (ad libitum 10% sucrose and chow followed by amphetamine injection, cyclic chow followed by amphetamine injection, ad libitum chow with amphetamine, or cyclic 10% sucrose and chow with a saline injection). These results suggest that a diet comprised of alternating deprivation and access to a sugar solution and chow produces bingeing on sugar that leads to a long lasting state of increased sensitivity to amphetamine, possibly due to a lasting alteration in the dopamine system.","[{'text': 'sugar dependency', 'type': 'Disease', 'start': 17, 'end': 33, 'mesh': 'D019966'}, {'text': 'behavioral cross-sensitization', 'type': 'Disease', 'start': 41, 'end': 71, 'mesh': 'D006948'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 89, 'end': 100, 'mesh': 'D000661'}, {'text': 'drug dependency', 'type': 'Disease', 'start': 272, 'end': 287, 'mesh': 'D019966'}, {'text': 'behavioral cross-sensitization', 'type': 'Disease', 'start': 383, 'end': 413, 'mesh': 'D006948'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 431, 'end': 442, 'mesh': 'D000661'}, {'text': 'sucrose', 'type': 'Chemical', 'start': 599, 'end': 606, 'mesh': 'D013395'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 954, 'end': 965, 'mesh': 'D000661'}, {'text': 'sucrose', 'type': 'Chemical', 'start': 1019, 'end': 1026, 'mesh': 'D013395'}, {'text': 'hyperactive', 'type': 'Disease', 'start': 1041, 'end': 1052, 'mesh': 'D006948'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1068, 'end': 1079, 'mesh': 'D000661'}, {'text': 'sucrose', 'type': 'Chemical', 'start': 1130, 'end': 1137, 'mesh': 'D013395'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1159, 'end': 1170, 'mesh': 'D000661'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1206, 'end': 1217, 'mesh': 'D000661'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1250, 'end': 1261, 'mesh': 'D000661'}, {'text': 'sucrose', 'type': 'Chemical', 'start': 1277, 'end': 1284, 'mesh': 'D013395'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1521, 'end': 1532, 'mesh': 'D000661'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1578, 'end': 1586, 'mesh': 'D004298'}]"
+357,6666578,D-penicillamine-induced angiopathy in rats. The effect of high dose D-penicillamine treatment on aortic permeability to albumin and on the ultrastructure of the vessel.,"Male Sprague-Dawley rats were treated with D-penicillamine (D-pen) 500 mg/kg/day for 10 or 42 days. Pair fed rats served as controls. Changes in aortic morphology were examined by light- and transmission-electron microscopy (TEM). In addition, the endothelial permeability and the penetration through the aortic wall of albumin were studied 10 minutes, 24 and 48 hours after i. v. injection of human serum 131I-albumin (131I-HSA). TEM revealed extensive elastolysis in the arterial wall of D-pen-treated rats, consistent with an inhibitory effect on crosslink formation. In experimental animals excess deposition of collagen and glycoaminoglycans was observed in the subendothelial and medial layer of the aortic wall, together with prominent basal membrane substance around aortic smooth muscle cells. The aorta/serum-ratio and the radioactive build-up 24 and 48 hours after injection of 131I-HSA was reduced in animals treated with D-pen for 42 days, indicating an impeded transmural transport of tracer which may be caused by a steric exclusion effect of abundant hyaluronate. The endothelial ultrastructure was unaffected by D-pen, and no differences in aortic 131I-HSA radioactivity or aorta/serum-ratio were recorded between experimental and control groups 10 minutes after tracer injection, indicating that the permeability of the endothelial barrier to albumin remained unaffected by D-pen treatment. These observations support the hypothesis that treatment with high doses of D-pen may induce a fibroproliferative response in rat aorta, possibly by an inhibitory effect on the cross-linking of collagen and elastin.","[{'text': 'D-penicillamine', 'type': 'Chemical', 'start': 0, 'end': 15, 'mesh': 'D010396'}, {'text': 'angiopathy', 'type': 'Disease', 'start': 24, 'end': 34, 'mesh': 'D001018'}, {'text': 'D-penicillamine', 'type': 'Chemical', 'start': 68, 'end': 83, 'mesh': 'D010396'}, {'text': 'D-penicillamine', 'type': 'Chemical', 'start': 212, 'end': 227, 'mesh': 'D010396'}, {'text': 'D-pen', 'type': 'Chemical', 'start': 229, 'end': 234, 'mesh': 'D010396'}, {'text': 'D-pen', 'type': 'Chemical', 'start': 659, 'end': 664, 'mesh': 'D010396'}, {'text': 'D-pen', 'type': 'Chemical', 'start': 1103, 'end': 1108, 'mesh': 'D010396'}, {'text': 'hyaluronate', 'type': 'Chemical', 'start': 1236, 'end': 1247, 'mesh': 'D006820'}, {'text': 'D-pen', 'type': 'Chemical', 'start': 1298, 'end': 1303, 'mesh': 'D010396'}, {'text': 'D-pen', 'type': 'Chemical', 'start': 1561, 'end': 1566, 'mesh': 'D010396'}, {'text': 'D-pen', 'type': 'Chemical', 'start': 1654, 'end': 1659, 'mesh': 'D010396'}]"
+358,11279304,Brain natriuretic peptide is a predictor of anthracycline-induced cardiotoxicity.,"Anthracyclines are effective antineoplastic drugs, but they frequently cause dose-related cardiotoxicity. The cardiotoxicity of conventional anthracycline therapy highlights a need to search for methods that are highly sensitive and capable of predicting cardiac dysfunction. We measured the plasma level of brain natriuretic peptide (BNP) to determine whether BNP might serve as a simple diagnostic indicator of anthracycline-induced cardiotoxicity in patients with acute leukemia treated with a daunorubicin (DNR)-containing regimen. Thirteen patients with acute leukemia were treated with a DNR-containing regimen. Cardiac functions were evaluated with radionuclide angiography before chemotherapies. The plasma levels of atrial natriuretic peptide (ANP) and BNP were measured at the time of radionuclide angiography. Three patients developed congestive heart failure after the completion of chemotherapy. Five patients were diagnosed as having subclinical heart failure after the completion of chemotherapy. The plasma levels of BNP in all the patients with clinical and subclinical heart failure increased above the normal limit (40 pg/ml) before the detection of clinical or subclinical heart failure by radionuclide angiography. On the other hand, BNP did not increase in the patients without heart failure given DNR, even at more than 700 mg/m(2). The plasma level of ANP did not always increase in all the patients with clinical and subclinical heart failure. These preliminary results suggest that BNP may be useful as an early and sensitive indicator of anthracycline-induced cardiotoxicity.","[{'text': 'anthracycline', 'type': 'Chemical', 'start': 44, 'end': 57, 'mesh': 'D018943'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 66, 'end': 80, 'mesh': 'D066126'}, {'text': 'Anthracyclines', 'type': 'Chemical', 'start': 82, 'end': 96, 'mesh': 'D018943'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 172, 'end': 186, 'mesh': 'D066126'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 192, 'end': 206, 'mesh': 'D066126'}, {'text': 'anthracycline', 'type': 'Chemical', 'start': 223, 'end': 236, 'mesh': 'D018943'}, {'text': 'cardiac dysfunction', 'type': 'Disease', 'start': 337, 'end': 356, 'mesh': 'D006331'}, {'text': 'anthracycline', 'type': 'Chemical', 'start': 495, 'end': 508, 'mesh': 'D018943'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 517, 'end': 531, 'mesh': 'D066126'}, {'text': 'acute leukemia', 'type': 'Disease', 'start': 549, 'end': 563, 'mesh': 'D015470'}, {'text': 'daunorubicin', 'type': 'Chemical', 'start': 579, 'end': 591, 'mesh': 'D003630'}, {'text': 'DNR', 'type': 'Chemical', 'start': 593, 'end': 596, 'mesh': 'D003630'}, {'text': 'acute leukemia', 'type': 'Disease', 'start': 641, 'end': 655, 'mesh': 'D015470'}, {'text': 'DNR', 'type': 'Chemical', 'start': 676, 'end': 679, 'mesh': 'D003630'}, {'text': 'congestive heart failure', 'type': 'Disease', 'start': 928, 'end': 952, 'mesh': 'D006333'}, {'text': 'heart failure', 'type': 'Disease', 'start': 1042, 'end': 1055, 'mesh': 'D006333'}, {'text': 'heart failure', 'type': 'Disease', 'start': 1169, 'end': 1182, 'mesh': 'D006333'}, {'text': 'heart failure', 'type': 'Disease', 'start': 1275, 'end': 1288, 'mesh': 'D006333'}, {'text': 'heart failure', 'type': 'Disease', 'start': 1382, 'end': 1395, 'mesh': 'D006333'}, {'text': 'DNR', 'type': 'Chemical', 'start': 1402, 'end': 1405, 'mesh': 'D003630'}, {'text': 'heart failure', 'type': 'Disease', 'start': 1536, 'end': 1549, 'mesh': 'D006333'}, {'text': 'anthracycline', 'type': 'Chemical', 'start': 1647, 'end': 1660, 'mesh': 'D018943'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1669, 'end': 1683, 'mesh': 'D066126'}]"
+359,19884587,Antibacterial medication use during pregnancy and risk of birth defects: National Birth Defects Prevention Study.,"OBJECTIVE: To estimate the association between antibacterial medications and selected birth defects. DESIGN, SETTING, AND PARTICIPANTS: Population-based, multisite, case-control study of women who had pregnancies affected by 1 of more than 30 eligible major birth defects identified via birth defect surveillance programs in 10 states (n = 13 155) and control women randomly selected from the same geographical regions (n = 4941). MAIN EXPOSURE: Reported maternal use of antibacterials (1 month before pregnancy through the end of the first trimester). MAIN OUTCOME MEASURE: Odds ratios (ORs) measuring the association between antibacterial use and selected birth defects adjusted for potential confounders. RESULTS: The reported use of antibacterials increased during pregnancy, peaking during the third month. Sulfonamides were associated with anencephaly (adjusted OR [AOR] = 3.4; 95% confidence interval [CI], 1.3-8.8), hypoplastic left heart syndrome (AOR = 3.2; 95% CI, 1.3-7.6), coarctation of the aorta (AOR = 2.7; 95% CI, 1.3-5.6), choanal atresia (AOR = 8.0; 95% CI, 2.7-23.5), transverse limb deficiency (AOR = 2.5; 95% CI, 1.0-5.9), and diaphragmatic hernia (AOR = 2.4; 95% CI, 1.1-5.4). Nitrofurantoins were associated with anophthalmia or microphthalmos (AOR = 3.7; 95% CI, 1.1-12.2), hypoplastic left heart syndrome (AOR = 4.2; 95% CI, 1.9-9.1), atrial septal defects (AOR = 1.9; 95% CI, 1.1-3.4), and cleft lip with cleft palate (AOR = 2.1; 95% CI, 1.2-3.9). Other antibacterial agents that showed associations included erythromycins (2 defects), penicillins (1 defect), cephalosporins (1 defect), and quinolones (1 defect). CONCLUSIONS: Reassuringly, penicillins, erythromycins, and cephalosporins, although used commonly by pregnant women, were not associated with many birth defects. Sulfonamides and nitrofurantoins were associated with several birth defects, indicating a need for additional scrutiny.","[{'text': 'birth defects', 'type': 'Disease', 'start': 58, 'end': 71, 'mesh': 'D000014'}, {'text': 'Birth Defects', 'type': 'Disease', 'start': 82, 'end': 95, 'mesh': 'D000014'}, {'text': 'birth defects', 'type': 'Disease', 'start': 200, 'end': 213, 'mesh': 'D000014'}, {'text': 'birth defects', 'type': 'Disease', 'start': 372, 'end': 385, 'mesh': 'D000014'}, {'text': 'birth defect', 'type': 'Disease', 'start': 401, 'end': 413, 'mesh': 'D000014'}, {'text': 'birth defects', 'type': 'Disease', 'start': 772, 'end': 785, 'mesh': 'D000014'}, {'text': 'Sulfonamides', 'type': 'Chemical', 'start': 926, 'end': 938, 'mesh': 'D013449'}, {'text': 'anencephaly', 'type': 'Disease', 'start': 960, 'end': 971, 'mesh': 'D000757'}, {'text': 'hypoplastic left heart syndrome', 'type': 'Disease', 'start': 1038, 'end': 1069, 'mesh': 'D018636'}, {'text': 'coarctation of the aorta', 'type': 'Disease', 'start': 1100, 'end': 1124, 'mesh': 'D001017'}, {'text': 'choanal atresia', 'type': 'Disease', 'start': 1155, 'end': 1170, 'mesh': 'D002754'}, {'text': 'transverse limb deficiency', 'type': 'Disease', 'start': 1202, 'end': 1228, 'mesh': 'D017880'}, {'text': 'diaphragmatic hernia', 'type': 'Disease', 'start': 1263, 'end': 1283, 'mesh': 'D006548'}, {'text': 'Nitrofurantoins', 'type': 'Chemical', 'start': 1314, 'end': 1329, 'mesh': 'D009582'}, {'text': 'anophthalmia', 'type': 'Disease', 'start': 1351, 'end': 1363, 'mesh': 'D000853'}, {'text': 'microphthalmos', 'type': 'Disease', 'start': 1367, 'end': 1381, 'mesh': 'D008850'}, {'text': 'hypoplastic left heart syndrome', 'type': 'Disease', 'start': 1413, 'end': 1444, 'mesh': 'D018636'}, {'text': 'atrial septal defects', 'type': 'Disease', 'start': 1475, 'end': 1496, 'mesh': 'D006344'}, {'text': 'cleft lip', 'type': 'Disease', 'start': 1531, 'end': 1540, 'mesh': 'D002971'}, {'text': 'cleft palate', 'type': 'Disease', 'start': 1546, 'end': 1558, 'mesh': 'D002972'}, {'text': 'erythromycins', 'type': 'Chemical', 'start': 1650, 'end': 1663, 'mesh': 'D004917'}, {'text': 'penicillins', 'type': 'Chemical', 'start': 1677, 'end': 1688, 'mesh': 'D010406'}, {'text': 'cephalosporins', 'type': 'Chemical', 'start': 1701, 'end': 1715, 'mesh': 'D002511'}, {'text': 'quinolones', 'type': 'Chemical', 'start': 1732, 'end': 1742, 'mesh': 'D015363'}, {'text': 'penicillins', 'type': 'Chemical', 'start': 1782, 'end': 1793, 'mesh': 'D010406'}, {'text': 'erythromycins', 'type': 'Chemical', 'start': 1795, 'end': 1808, 'mesh': 'D004917'}, {'text': 'cephalosporins', 'type': 'Chemical', 'start': 1814, 'end': 1828, 'mesh': 'D002511'}, {'text': 'birth defects', 'type': 'Disease', 'start': 1902, 'end': 1915, 'mesh': 'D000014'}, {'text': 'Sulfonamides', 'type': 'Chemical', 'start': 1917, 'end': 1929, 'mesh': 'D013449'}, {'text': 'nitrofurantoins', 'type': 'Chemical', 'start': 1934, 'end': 1949, 'mesh': 'D009582'}, {'text': 'birth defects', 'type': 'Disease', 'start': 1979, 'end': 1992, 'mesh': 'D000014'}]"
+360,3970039,Incidence of neoplasms in patients with rheumatoid arthritis exposed to different treatment regimens.,"Immunosuppressive drugs have been used during the last 30 years in treatment of patients with severe rheumatoid arthritis. The drugs commonly used are cyclophosphamide and chlorambucil (alkylating agents), azathioprine (purine analogue), and methotrexate (folic acid analogue). There is evidence that all four immunosuppressive drugs can reduce synovitis, but disease activity almost always recurs after therapy is stopped. Since adverse reactions are frequent, less than 50 percent of patients are able to continue a particular drug for more than one year. Since it takes three to 12 months to achieve maximal effects, those patients who are unable to continue the drug receive little benefit from it. Patients treated with alkylating agents have an increased risk of development of acute nonlymphocytic leukemia, and both alkylating agents and azathioprine are associated with the development of non-Hodgkin's lymphoma. Cyclophosphamide therapy increases the risk of carcinoma of the bladder. There have been several long-term studies of patients with rheumatoid arthritis treated with azathioprine and cyclophosphamide and the incidence of most of the common cancers is not increased. Data on the possible increased risk of malignancy in rheumatoid arthritis are still being collected, and until further information is available, the use of immunosuppressive drugs, particularly alkylating agents, in the treatment of rheumatoid arthritis should be reserved for patients with severe progressive disease or life-threatening complications.","[{'text': 'neoplasms', 'type': 'Disease', 'start': 13, 'end': 22, 'mesh': 'D009369'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 40, 'end': 60, 'mesh': 'D001172'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 203, 'end': 223, 'mesh': 'D001172'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 253, 'end': 269, 'mesh': 'D003520'}, {'text': 'chlorambucil', 'type': 'Chemical', 'start': 274, 'end': 286, 'mesh': 'D002699'}, {'text': 'alkylating agents', 'type': 'Chemical', 'start': 288, 'end': 305, 'mesh': 'D000477'}, {'text': 'azathioprine', 'type': 'Chemical', 'start': 308, 'end': 320, 'mesh': 'D001379'}, {'text': 'purine', 'type': 'Chemical', 'start': 322, 'end': 328, 'mesh': 'D011687'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 344, 'end': 356, 'mesh': 'D008727'}, {'text': 'folic acid', 'type': 'Chemical', 'start': 358, 'end': 368, 'mesh': 'D005492'}, {'text': 'synovitis', 'type': 'Disease', 'start': 447, 'end': 456, 'mesh': 'D013585'}, {'text': 'alkylating agents', 'type': 'Chemical', 'start': 827, 'end': 844, 'mesh': 'D000477'}, {'text': 'acute nonlymphocytic leukemia', 'type': 'Disease', 'start': 886, 'end': 915, 'mesh': 'D015470'}, {'text': 'alkylating agents', 'type': 'Chemical', 'start': 926, 'end': 943, 'mesh': 'D000477'}, {'text': 'azathioprine', 'type': 'Chemical', 'start': 948, 'end': 960, 'mesh': 'D001379'}, {'text': ""non-Hodgkin's lymphoma"", 'type': 'Disease', 'start': 1000, 'end': 1022, 'mesh': 'D008228'}, {'text': 'Cyclophosphamide', 'type': 'Chemical', 'start': 1024, 'end': 1040, 'mesh': 'D003520'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 1156, 'end': 1176, 'mesh': 'D001172'}, {'text': 'azathioprine', 'type': 'Chemical', 'start': 1190, 'end': 1202, 'mesh': 'D001379'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 1207, 'end': 1223, 'mesh': 'D003520'}, {'text': 'cancers', 'type': 'Disease', 'start': 1264, 'end': 1271, 'mesh': 'D009369'}, {'text': 'malignancy', 'type': 'Disease', 'start': 1329, 'end': 1339, 'mesh': 'D009369'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 1343, 'end': 1363, 'mesh': 'D001172'}, {'text': 'alkylating agents', 'type': 'Chemical', 'start': 1484, 'end': 1501, 'mesh': 'D000477'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 1523, 'end': 1543, 'mesh': 'D001172'}]"
+361,424937,Patterns of hepatic injury induced by methyldopa.,"Twelve patients with liver disease related to methyldopa were seen between 1967 and 1977. Illness occurred within 1--9 weeks of commencement of therapy in 9 patients, the remaining 3 patients having received the drug for 13 months, 15 months and 7 years before experiencing symptoms. Jaundice with tender hepatomegaly, usually preceded by symptoms of malaise, anorexia, nausea and vomiting, and associated with upper abdominal pain, was an invariable finding in all patients. Biochemical liver function tests indicated hepatocellular necrosis and correlated with histopathological evidence of hepatic injury, the spectrum of which ranged from fatty change and focal hepatocellular necrosis to massive hepatic necrosis. Most patients showed moderate to severe acute hepatitis or chronic active hepatitis with associated cholestasis. The drug was withdrawn on presentation to hospital in 11 patients, with rapid clinical improvement in 9. One patient died, having presented in hepatic failure, and another, who had been taking methyldopa for 7 years, showed slower clinical and biochemical resolution over a period of several months. The remaining patient in the series developed fulminant hepatitis when the drug was accidentally recommenced 1 year after a prior episode of methyldopa-induced hepatitis. In this latter patient, and in 2 others, the causal relationship between methyldopa and hepatic dysfunction was proved with the recurrence of hepatitis within 2 weeks of re-exposure to the drug.","[{'text': 'hepatic injury', 'type': 'Disease', 'start': 12, 'end': 26, 'mesh': 'D056486'}, {'text': 'methyldopa', 'type': 'Chemical', 'start': 38, 'end': 48, 'mesh': 'D008750'}, {'text': 'liver disease', 'type': 'Disease', 'start': 71, 'end': 84, 'mesh': 'D008107'}, {'text': 'methyldopa', 'type': 'Chemical', 'start': 96, 'end': 106, 'mesh': 'D008750'}, {'text': 'Jaundice', 'type': 'Disease', 'start': 334, 'end': 342, 'mesh': 'D007565'}, {'text': 'hepatomegaly', 'type': 'Disease', 'start': 355, 'end': 367, 'mesh': 'D006529'}, {'text': 'anorexia', 'type': 'Disease', 'start': 410, 'end': 418, 'mesh': 'D000855'}, {'text': 'nausea', 'type': 'Disease', 'start': 420, 'end': 426, 'mesh': 'D009325'}, {'text': 'vomiting', 'type': 'Disease', 'start': 431, 'end': 439, 'mesh': 'D014839'}, {'text': 'abdominal pain', 'type': 'Disease', 'start': 467, 'end': 481, 'mesh': 'D015746'}, {'text': 'necrosis', 'type': 'Disease', 'start': 584, 'end': 592, 'mesh': 'D009336'}, {'text': 'hepatic injury', 'type': 'Disease', 'start': 643, 'end': 657, 'mesh': 'D056486'}, {'text': 'fatty change', 'type': 'Disease', 'start': 693, 'end': 705, 'mesh': 'D005234'}, {'text': 'necrosis', 'type': 'Disease', 'start': 731, 'end': 739, 'mesh': 'D009336'}, {'text': 'massive hepatic necrosis', 'type': 'Disease', 'start': 743, 'end': 767, 'mesh': 'D047508'}, {'text': 'acute hepatitis', 'type': 'Disease', 'start': 809, 'end': 824, 'mesh': 'D017114'}, {'text': 'chronic active hepatitis', 'type': 'Disease', 'start': 828, 'end': 852, 'mesh': 'D006521'}, {'text': 'cholestasis', 'type': 'Disease', 'start': 869, 'end': 880, 'mesh': 'D002779'}, {'text': 'hepatic failure', 'type': 'Disease', 'start': 1025, 'end': 1040, 'mesh': 'D017093'}, {'text': 'methyldopa', 'type': 'Chemical', 'start': 1075, 'end': 1085, 'mesh': 'D008750'}, {'text': 'fulminant hepatitis', 'type': 'Disease', 'start': 1228, 'end': 1247, 'mesh': 'D017114'}, {'text': 'methyldopa', 'type': 'Chemical', 'start': 1323, 'end': 1333, 'mesh': 'D008750'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 1342, 'end': 1351, 'mesh': 'D056486'}, {'text': 'methyldopa', 'type': 'Chemical', 'start': 1426, 'end': 1436, 'mesh': 'D008750'}, {'text': 'hepatic dysfunction', 'type': 'Disease', 'start': 1441, 'end': 1460, 'mesh': 'D008107'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 1495, 'end': 1504, 'mesh': 'D056486'}]"
+362,8643971,A phase I/II study of paclitaxel plus cisplatin as first-line therapy for head and neck cancers: preliminary results.,"Improved outcomes among patients with head and neck carcinomas require investigations of new drugs for induction therapy. Preliminary results of an Eastern Cooperative Oncology Group study of single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) reported a 37% response rate in patients with head and neck cancer, and the paclitaxel/cisplatin combination has been used successfully and has significantly improved median response duration in ovarian cancer patients. We initiated a phase I/II trial to determine the response and toxicity of escalating paclitaxel doses combined with fixed-dose cisplatin with granulocyte colony-stimulating factor support in patients with untreated locally advanced inoperable head and neck carcinoma. To date, 23 men with a median age of 50 years and good performance status have entered the trial. Primary tumor sites were oropharynx, 10 patients; hypopharynx, four; larynx, two; oral cavity, three; unknown primary, two; and nasal cavity and parotid gland, one each. Of 20 patients evaluable for toxicity, four had stage III and 16 had stage IV disease. Treatment, given every 21 days for a maximum of three cycles, consisted of paclitaxel by 3-hour infusion followed the next day by a fixed dose of cisplatin (75 mg/m2). The dose levels incorporate escalating paclitaxel doses, and intrapatient escalations within a given dose level are permitted if toxicity permits. At the time of this writing, dose level 4 (260, 270, and 280 mg/m2) is being evaluated; three patients from this level are evaluable. With paclitaxel doses of 200 mg/m2 and higher, granulocyte colony-stimulating factor 5 micrograms/kg/d is given (days 4 through 12). Of 18 patients evaluable for response, seven (39%) achieved a complete response and six (33%) achieved a partial response. Three patients had no change and disease progressed in two. The overall response rate is 72%. Eleven responding patients had subsequent surgery/radiotherapy or radical radiotherapy. Two pathologic complete responses were observed in patients who had achieved clinical complete responses. Alopecia, paresthesias, and arthralgias/myalgias have occurred frequently, but with one exception (a grade 3 myalgia) they have been grade 1 or 2. No dose-limiting hematologic toxicity has been seen. Paclitaxel/cisplatin is an effective first-line regimen for locoregionally advanced head and neck cancer and continued study is warranted. Results thus far suggest no dose-response effect for paclitaxel doses above 200 mg/m2.","[{'text': 'paclitaxel', 'type': 'Chemical', 'start': 22, 'end': 32, 'mesh': 'D017239'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 38, 'end': 47, 'mesh': 'D002945'}, {'text': 'head and neck cancers', 'type': 'Disease', 'start': 74, 'end': 95, 'mesh': 'D006258'}, {'text': 'head and neck carcinomas', 'type': 'Disease', 'start': 156, 'end': 180, 'mesh': 'D006258'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 323, 'end': 333, 'mesh': 'D017239'}, {'text': 'Taxol', 'type': 'Chemical', 'start': 335, 'end': 340, 'mesh': 'D017239'}, {'text': 'head and neck cancer', 'type': 'Disease', 'start': 433, 'end': 453, 'mesh': 'D006258'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 463, 'end': 473, 'mesh': 'D017239'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 474, 'end': 483, 'mesh': 'D002945'}, {'text': 'ovarian cancer', 'type': 'Disease', 'start': 582, 'end': 596, 'mesh': 'D010051'}, {'text': 'toxicity', 'type': 'Disease', 'start': 669, 'end': 677, 'mesh': 'D064420'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 692, 'end': 702, 'mesh': 'D017239'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 734, 'end': 743, 'mesh': 'D002945'}, {'text': 'head and neck carcinoma', 'type': 'Disease', 'start': 850, 'end': 873, 'mesh': 'D006258'}, {'text': 'tumor', 'type': 'Disease', 'start': 981, 'end': 986, 'mesh': 'D009369'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1172, 'end': 1180, 'mesh': 'D064420'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 1305, 'end': 1315, 'mesh': 'D017239'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 1376, 'end': 1385, 'mesh': 'D002945'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 1437, 'end': 1447, 'mesh': 'D017239'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1527, 'end': 1535, 'mesh': 'D064420'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 1684, 'end': 1694, 'mesh': 'D017239'}, {'text': 'Alopecia', 'type': 'Disease', 'start': 2223, 'end': 2231, 'mesh': 'D000505'}, {'text': 'paresthesias', 'type': 'Disease', 'start': 2233, 'end': 2245, 'mesh': 'D010292'}, {'text': 'arthralgias', 'type': 'Disease', 'start': 2251, 'end': 2262, 'mesh': 'D018771'}, {'text': 'myalgias', 'type': 'Disease', 'start': 2263, 'end': 2271, 'mesh': 'D063806'}, {'text': 'myalgia', 'type': 'Disease', 'start': 2332, 'end': 2339, 'mesh': 'D063806'}, {'text': 'toxicity', 'type': 'Disease', 'start': 2399, 'end': 2407, 'mesh': 'D064420'}, {'text': 'Paclitaxel', 'type': 'Chemical', 'start': 2423, 'end': 2433, 'mesh': 'D017239'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 2434, 'end': 2443, 'mesh': 'D002945'}, {'text': 'head and neck cancer', 'type': 'Disease', 'start': 2507, 'end': 2527, 'mesh': 'D006258'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 2615, 'end': 2625, 'mesh': 'D017239'}]"
+363,2224762,A phase I study of 4'-0-tetrahydropyranyladriamycin. Clinical pharmacology and pharmacokinetics.,"A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.","[{'text': ""4'-0-tetrahydropyranyladriamycin"", 'type': 'Chemical', 'start': 19, 'end': 51, 'mesh': 'C027260'}, {'text': ""4'-0-tetrahydropyranyladriamycin"", 'type': 'Chemical', 'start': 139, 'end': 171, 'mesh': 'C027260'}, {'text': 'Pirarubicin', 'type': 'Chemical', 'start': 173, 'end': 184, 'mesh': 'C027260'}, {'text': 'tumors', 'type': 'Disease', 'start': 253, 'end': 259, 'mesh': 'D009369'}, {'text': 'granulocytopenia', 'type': 'Disease', 'start': 622, 'end': 638, 'mesh': 'D000380'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 724, 'end': 740, 'mesh': 'D013921'}, {'text': 'anemia', 'type': 'Disease', 'start': 742, 'end': 748, 'mesh': 'D000740'}, {'text': 'nausea', 'type': 'Disease', 'start': 750, 'end': 756, 'mesh': 'D009325'}, {'text': 'alopecia', 'type': 'Disease', 'start': 763, 'end': 771, 'mesh': 'D000505'}, {'text': 'phlebitis', 'type': 'Disease', 'start': 773, 'end': 782, 'mesh': 'D010689'}, {'text': 'mucositis', 'type': 'Disease', 'start': 788, 'end': 797, 'mesh': 'D052016'}, {'text': 'Myelosuppression', 'type': 'Disease', 'start': 799, 'end': 815, 'mesh': 'D001855'}, {'text': 'hepatic dysfunction', 'type': 'Disease', 'start': 842, 'end': 861, 'mesh': 'D008107'}, {'text': 'Pirarubicin', 'type': 'Chemical', 'start': 912, 'end': 923, 'mesh': 'C027260'}, {'text': 'Adriamycinol', 'type': 'Chemical', 'start': 1207, 'end': 1219, 'mesh': 'C010013'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1221, 'end': 1232, 'mesh': 'D004317'}, {'text': 'adriamycinone', 'type': 'Chemical', 'start': 1234, 'end': 1247, 'mesh': 'C010012'}, {'text': 'tetrahydropyranyladriamycinol', 'type': 'Chemical', 'start': 1253, 'end': 1282, 'mesh': 'C027260'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1341, 'end': 1352, 'mesh': 'D004317'}, {'text': 'Pirarubicin', 'type': 'Chemical', 'start': 1430, 'end': 1441, 'mesh': 'C027260'}, {'text': 'mesothelioma', 'type': 'Disease', 'start': 1517, 'end': 1529, 'mesh': 'D008654'}, {'text': 'leiomyosarcoma', 'type': 'Disease', 'start': 1531, 'end': 1545, 'mesh': 'D007890'}, {'text': 'basal cell carcinoma', 'type': 'Disease', 'start': 1551, 'end': 1571, 'mesh': 'D002280'}]"
+364,2440413,Differential effects of gamma-hexachlorocyclohexane (lindane) on pharmacologically-induced seizures.,"Gamma-hexachlorocyclohexane (gamma-HCH), the active ingredient of the insecticide lindane, has been shown to decrease seizure threshold to pentylenetrazol (PTZ) 3 h after exposure to gamma-HCH and conversely increase threshold to PTZ-induced seizures 24 h after exposure to gamma-HCH (Vohland et al. 1981). In this study, the severity of response to other seizure-inducing agents was tested in mice 1 and 24 h after intraperitoneal administration of 80 mg/kg gamma-HCH. One hour after the administration of gamma-HCH, the activity of seizure-inducing agents was increased, regardless of their mechanism, while 24 h after gamma-HCH a differential response was observed. Seizure activity due to PTZ and picrotoxin (PTX) was significantly decreased; however, seizure activity due to 3-mercaptopropionic acid (MPA), bicuculline (BCC), methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate (DMCM), or strychnine (STR) was not different from control. In vitro, gamma-HCH, pentylenetetrazol and picrotoxin were shown to inhibit 3H-TBOB binding in mouse whole brain, with IC50 values of 4.6, 404 and 9.4 microM, respectively. MPA, BCC, DMCM, and STR showed no inhibition of 3H-TBOB (t-butyl bicyclo-orthobenzoate) binding at concentrations of 100 micron. The pharmacological challenge data suggest that tolerance may occur to seizure activity induced by PTZ and PTX 24 h after gamma-HCH, since the response to only these two seizure-inducing agents is decreased. The in vitro data suggest that the site responsible for the decrease in seizure activity 24 h after gamma-HCH may be the GABA-A receptor-linked chloride channel.","[{'text': 'gamma-hexachlorocyclohexane', 'type': 'Chemical', 'start': 24, 'end': 51, 'mesh': 'D001556'}, {'text': 'lindane', 'type': 'Chemical', 'start': 53, 'end': 60, 'mesh': 'D001556'}, {'text': 'seizures', 'type': 'Disease', 'start': 91, 'end': 99, 'mesh': 'D012640'}, {'text': 'Gamma-hexachlorocyclohexane', 'type': 'Chemical', 'start': 101, 'end': 128, 'mesh': 'D001556'}, {'text': 'gamma-HCH', 'type': 'Chemical', 'start': 130, 'end': 139, 'mesh': 'D001556'}, {'text': 'lindane', 'type': 'Chemical', 'start': 183, 'end': 190, 'mesh': 'D001556'}, {'text': 'seizure', 'type': 'Disease', 'start': 219, 'end': 226, 'mesh': 'D012640'}, {'text': 'PTZ', 'type': 'Chemical', 'start': 257, 'end': 260, 'mesh': 'D010433'}, {'text': 'gamma-HCH', 'type': 'Chemical', 'start': 284, 'end': 293, 'mesh': 'D001556'}, {'text': 'PTZ', 'type': 'Chemical', 'start': 331, 'end': 334, 'mesh': 'D010433'}, {'text': 'seizures', 'type': 'Disease', 'start': 343, 'end': 351, 'mesh': 'D012640'}, {'text': 'gamma-HCH', 'type': 'Chemical', 'start': 375, 'end': 384, 'mesh': 'D001556'}, {'text': 'seizure', 'type': 'Disease', 'start': 457, 'end': 464, 'mesh': 'D012640'}, {'text': 'gamma-HCH', 'type': 'Chemical', 'start': 560, 'end': 569, 'mesh': 'D001556'}, {'text': 'gamma-HCH', 'type': 'Chemical', 'start': 608, 'end': 617, 'mesh': 'D001556'}, {'text': 'seizure', 'type': 'Disease', 'start': 635, 'end': 642, 'mesh': 'D012640'}, {'text': 'gamma-HCH', 'type': 'Chemical', 'start': 722, 'end': 731, 'mesh': 'D001556'}, {'text': 'Seizure', 'type': 'Disease', 'start': 770, 'end': 777, 'mesh': 'D012640'}, {'text': 'PTZ', 'type': 'Chemical', 'start': 794, 'end': 797, 'mesh': 'D010433'}, {'text': 'picrotoxin', 'type': 'Chemical', 'start': 802, 'end': 812, 'mesh': 'D010852'}, {'text': 'PTX', 'type': 'Chemical', 'start': 814, 'end': 817, 'mesh': 'D010852'}, {'text': 'seizure', 'type': 'Disease', 'start': 857, 'end': 864, 'mesh': 'D012640'}, {'text': '3-mercaptopropionic acid', 'type': 'Chemical', 'start': 881, 'end': 905, 'mesh': 'D015097'}, {'text': 'MPA', 'type': 'Chemical', 'start': 907, 'end': 910, 'mesh': 'D015097'}, {'text': 'bicuculline', 'type': 'Chemical', 'start': 913, 'end': 924, 'mesh': 'D001640'}, {'text': 'BCC', 'type': 'Chemical', 'start': 926, 'end': 929, 'mesh': 'D001640'}, {'text': 'methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate', 'type': 'Chemical', 'start': 932, 'end': 986, 'mesh': 'C034818'}, {'text': 'DMCM', 'type': 'Chemical', 'start': 988, 'end': 992, 'mesh': 'C034818'}, {'text': 'strychnine', 'type': 'Chemical', 'start': 998, 'end': 1008, 'mesh': 'D013331'}, {'text': 'STR', 'type': 'Chemical', 'start': 1010, 'end': 1013, 'mesh': 'D013331'}, {'text': 'gamma-HCH', 'type': 'Chemical', 'start': 1057, 'end': 1066, 'mesh': 'D001556'}, {'text': 'pentylenetetrazol', 'type': 'Chemical', 'start': 1068, 'end': 1085, 'mesh': 'D010433'}, {'text': 'picrotoxin', 'type': 'Chemical', 'start': 1090, 'end': 1100, 'mesh': 'D010852'}, {'text': '3H-TBOB', 'type': 'Chemical', 'start': 1123, 'end': 1130, 'mesh': 'C046308'}, {'text': 'MPA', 'type': 'Chemical', 'start': 1220, 'end': 1223, 'mesh': 'D015097'}, {'text': 'BCC', 'type': 'Chemical', 'start': 1225, 'end': 1228, 'mesh': 'D001640'}, {'text': 'DMCM', 'type': 'Chemical', 'start': 1230, 'end': 1234, 'mesh': 'C034818'}, {'text': 'STR', 'type': 'Chemical', 'start': 1240, 'end': 1243, 'mesh': 'D013331'}, {'text': '3H-TBOB', 'type': 'Chemical', 'start': 1268, 'end': 1275, 'mesh': 'C046308'}, {'text': 't-butyl bicyclo-orthobenzoate', 'type': 'Chemical', 'start': 1277, 'end': 1306, 'mesh': 'C046308'}, {'text': 'seizure', 'type': 'Disease', 'start': 1420, 'end': 1427, 'mesh': 'D012640'}, {'text': 'PTZ', 'type': 'Chemical', 'start': 1448, 'end': 1451, 'mesh': 'D010433'}, {'text': 'PTX', 'type': 'Chemical', 'start': 1456, 'end': 1459, 'mesh': 'D010852'}, {'text': 'gamma-HCH', 'type': 'Chemical', 'start': 1471, 'end': 1480, 'mesh': 'D001556'}, {'text': 'seizure', 'type': 'Disease', 'start': 1519, 'end': 1526, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 1629, 'end': 1636, 'mesh': 'D012640'}, {'text': 'gamma-HCH', 'type': 'Chemical', 'start': 1657, 'end': 1666, 'mesh': 'D001556'}, {'text': 'GABA', 'type': 'Chemical', 'start': 1678, 'end': 1682, 'mesh': 'D005680'}]"
+365,12483326,Severe ocular and orbital toxicity after intracarotid injection of carboplatin for recurrent glioblastomas.,"BACKGROUND: Glioblastoma is a malignant tumor that occurs in the cerebrum during adulthood. With current treatment regimens including combined surgery, radiation and chemotherapy, the average life expectancy of the patients is limited to approximately 1 year. Therefore, patients with glioblastoma sometimes have intracarotid injection of carcinostatics added to the treatment regimen. Generally, carboplatin is said to have milder side effects than cisplatin, whose ocular and orbital toxicity are well known. However, we experienced a case of severe ocular and orbital toxicity after intracarotid injection of carboplatin, which is infrequently reported. CASE: A 58-year-old man received an intracarotid injection of carboplatin for recurrent glioblastomas in his left temporal lobe. He complained of pain and visual disturbance in the ipsilateral eye 30 h after the injection. Various ocular symptoms and findings caused by carboplatin toxicity were seen. RESULTS: He was treated with intravenous administration of corticosteroids and glycerin for 6 days after the injection. Although the intraocular pressure elevation caused by secondary acute angle-closure glaucoma decreased and ocular pain diminished, inexorable papilledema and exudative retinal detachment continued for 3 weeks. Finally, 6 weeks later, diffuse chorioretinal atrophy with optic atrophy occurred and the vision in his left eye was lost. CONCLUSION: When performing intracarotid injection of carboplatin, we must be aware of its potentially blinding ocular toxicity. It is recommended that further studies and investigations are undertaken in the effort to minimize such severe side effects.","[{'text': 'carboplatin', 'type': 'Chemical', 'start': 67, 'end': 78, 'mesh': 'D016190'}, {'text': 'glioblastomas', 'type': 'Disease', 'start': 93, 'end': 106, 'mesh': 'D005909'}, {'text': 'Glioblastoma', 'type': 'Disease', 'start': 120, 'end': 132, 'mesh': 'D005909'}, {'text': 'malignant tumor', 'type': 'Disease', 'start': 138, 'end': 153, 'mesh': 'D009369'}, {'text': 'glioblastoma', 'type': 'Disease', 'start': 393, 'end': 405, 'mesh': 'D005909'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 505, 'end': 516, 'mesh': 'D016190'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 558, 'end': 567, 'mesh': 'D002945'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 720, 'end': 731, 'mesh': 'D016190'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 827, 'end': 838, 'mesh': 'D016190'}, {'text': 'glioblastomas', 'type': 'Disease', 'start': 853, 'end': 866, 'mesh': 'D005909'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 1035, 'end': 1046, 'mesh': 'D016190'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1047, 'end': 1055, 'mesh': 'D064420'}, {'text': 'glycerin', 'type': 'Chemical', 'start': 1146, 'end': 1154, 'mesh': 'D005990'}, {'text': 'glaucoma', 'type': 'Disease', 'start': 1271, 'end': 1279, 'mesh': 'D005901'}, {'text': 'ocular pain', 'type': 'Disease', 'start': 1294, 'end': 1305, 'mesh': 'D058447'}, {'text': 'papilledema', 'type': 'Disease', 'start': 1329, 'end': 1340, 'mesh': 'D010211'}, {'text': 'retinal detachment', 'type': 'Disease', 'start': 1355, 'end': 1373, 'mesh': 'D012163'}, {'text': 'chorioretinal atrophy', 'type': 'Disease', 'start': 1429, 'end': 1450, 'mesh': 'C566236'}, {'text': 'optic atrophy', 'type': 'Disease', 'start': 1456, 'end': 1469, 'mesh': 'D009896'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 1574, 'end': 1585, 'mesh': 'D016190'}, {'text': 'ocular toxicity', 'type': 'Disease', 'start': 1632, 'end': 1647, 'mesh': 'D005128'}]"
+366,1664218,Phase II study of the amsacrine analogue CI-921 (NSC 343499) in non-small cell lung cancer.,"CI-921 (NSC 343499; 9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide) is a topoisomerase II poison with high experimental antitumour activity. It was administered by 15 min infusion to 16 evaluable patients with non-small cell lung cancer (NSCLC) (7 with no prior treatment, 9 patients in relapse following surgery/radiotherapy) at a dose (648 mg/m2 divided over 3 days, repeated every 3 weeks) determined by phase I trial. Patients had a median performance status of 1 (WHO), and median age of 61 years. The histology comprised squamous carcinoma (11), adenocarcinoma (1), mixed histology (2), bronchio-alveolar carcinoma (1) and large cell undifferentiated carcinoma (1). Neutropenia grade greater than or equal to 3 was seen in 15 patients, infections with recovery in 3, and grand mal seizures in 1 patient. Grade less than or equal to 2 nausea and vomiting occurred in 66% courses and phlebitis in the infusion arm in 37%. 1 patient with squamous cell carcinoma achieved a partial response lasting 5 months. Further testing in this and other tumour types using multiple daily schedules is warranted.","[{'text': 'amsacrine', 'type': 'Chemical', 'start': 22, 'end': 31, 'mesh': 'D000677'}, {'text': 'CI-921', 'type': 'Chemical', 'start': 41, 'end': 47, 'mesh': 'C042315'}, {'text': 'NSC 343499', 'type': 'Chemical', 'start': 49, 'end': 59, 'mesh': 'C042315'}, {'text': 'non-small cell lung cancer', 'type': 'Disease', 'start': 64, 'end': 90, 'mesh': 'D002289'}, {'text': 'CI-921', 'type': 'Chemical', 'start': 92, 'end': 98, 'mesh': 'C042315'}, {'text': 'NSC 343499', 'type': 'Chemical', 'start': 100, 'end': 110, 'mesh': 'C042315'}, {'text': '9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide', 'type': 'Chemical', 'start': 112, 'end': 202, 'mesh': 'C042315'}, {'text': 'non-small cell lung cancer', 'type': 'Disease', 'start': 346, 'end': 372, 'mesh': 'D002289'}, {'text': 'NSCLC', 'type': 'Disease', 'start': 374, 'end': 379, 'mesh': 'D002289'}, {'text': 'squamous carcinoma', 'type': 'Disease', 'start': 663, 'end': 681, 'mesh': 'D002294'}, {'text': 'adenocarcinoma', 'type': 'Disease', 'start': 688, 'end': 702, 'mesh': 'D000230'}, {'text': 'bronchio-alveolar carcinoma', 'type': 'Disease', 'start': 729, 'end': 756, 'mesh': 'D002282'}, {'text': 'undifferentiated carcinoma', 'type': 'Disease', 'start': 776, 'end': 802, 'mesh': 'D002277'}, {'text': 'Neutropenia', 'type': 'Disease', 'start': 808, 'end': 819, 'mesh': 'D009503'}, {'text': 'infections', 'type': 'Disease', 'start': 878, 'end': 888, 'mesh': 'D007239'}, {'text': 'seizures', 'type': 'Disease', 'start': 923, 'end': 931, 'mesh': 'D012640'}, {'text': 'nausea', 'type': 'Disease', 'start': 976, 'end': 982, 'mesh': 'D009325'}, {'text': 'vomiting', 'type': 'Disease', 'start': 987, 'end': 995, 'mesh': 'D014839'}, {'text': 'phlebitis', 'type': 'Disease', 'start': 1024, 'end': 1033, 'mesh': 'D010689'}, {'text': 'squamous cell carcinoma', 'type': 'Disease', 'start': 1077, 'end': 1100, 'mesh': 'D002294'}, {'text': 'tumour', 'type': 'Disease', 'start': 1181, 'end': 1187, 'mesh': 'D009369'}]"
+367,18809400,Alpha-lipoic acid prevents mitochondrial damage and neurotoxicity in experimental chemotherapy neuropathy.,"The study investigates if alpha-lipoic acid is neuroprotective against chemotherapy induced neurotoxicity, if mitochondrial damage plays a critical role in toxic neurodegenerative cascade, and if neuroprotective effects of alpha-lipoic acid depend on mitochondria protection. We used an in vitro model of chemotherapy induced peripheral neuropathy that closely mimic the in vivo condition by exposing primary cultures of dorsal root ganglion (DRG) sensory neurons to paclitaxel and cisplatin, two widely used and highly effective chemotherapeutic drugs. This approach allowed investigating the efficacy of alpha-lipoic acid in preventing axonal damage and apoptosis and the function and ultrastructural morphology of mitochondria after exposure to toxic agents and alpha-lipoic acid. Our results demonstrate that both cisplatin and paclitaxel cause early mitochondrial impairment with loss of membrane potential and induction of autophagic vacuoles in neurons. Alpha-lipoic acid exerts neuroprotective effects against chemotherapy induced neurotoxicity in sensory neurons: it rescues the mitochondrial toxicity and induces the expression of frataxin, an essential mitochondrial protein with anti-oxidant and chaperone properties. In conclusion mitochondrial toxicity is an early common event both in paclitaxel and cisplatin induced neurotoxicity. Alpha-lipoic acid protects sensory neurons through its anti-oxidant and mitochondrial regulatory functions, possibly inducing the expression of frataxin. These findings suggest that alpha-lipoic acid might reduce the risk of developing peripheral nerve toxicity in patients undergoing chemotherapy and encourage further confirmatory clinical trials.","[{'text': 'Alpha-lipoic acid', 'type': 'Chemical', 'start': 0, 'end': 17, 'mesh': 'D008063'}, {'text': 'mitochondrial damage', 'type': 'Disease', 'start': 27, 'end': 47, 'mesh': 'D028361'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 52, 'end': 65, 'mesh': 'D020258'}, {'text': 'neuropathy', 'type': 'Disease', 'start': 95, 'end': 105, 'mesh': 'D009422'}, {'text': 'alpha-lipoic acid', 'type': 'Chemical', 'start': 133, 'end': 150, 'mesh': 'D008063'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 199, 'end': 212, 'mesh': 'D020258'}, {'text': 'mitochondrial damage', 'type': 'Disease', 'start': 217, 'end': 237, 'mesh': 'D028361'}, {'text': 'toxic neurodegenerative cascade', 'type': 'Disease', 'start': 263, 'end': 294, 'mesh': 'D009410'}, {'text': 'alpha-lipoic acid', 'type': 'Chemical', 'start': 330, 'end': 347, 'mesh': 'D008063'}, {'text': 'peripheral neuropathy', 'type': 'Disease', 'start': 433, 'end': 454, 'mesh': 'D010523'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 574, 'end': 584, 'mesh': 'D017239'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 589, 'end': 598, 'mesh': 'D002945'}, {'text': 'alpha-lipoic acid', 'type': 'Chemical', 'start': 713, 'end': 730, 'mesh': 'D008063'}, {'text': 'axonal damage', 'type': 'Disease', 'start': 745, 'end': 758, 'mesh': 'D001480'}, {'text': 'alpha-lipoic acid', 'type': 'Chemical', 'start': 872, 'end': 889, 'mesh': 'D008063'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 925, 'end': 934, 'mesh': 'D002945'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 939, 'end': 949, 'mesh': 'D017239'}, {'text': 'mitochondrial impairment', 'type': 'Disease', 'start': 962, 'end': 986, 'mesh': 'D028361'}, {'text': 'Alpha-lipoic acid', 'type': 'Chemical', 'start': 1068, 'end': 1085, 'mesh': 'D008063'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 1146, 'end': 1159, 'mesh': 'D020258'}, {'text': 'mitochondrial toxicity', 'type': 'Disease', 'start': 1195, 'end': 1217, 'mesh': 'D028361'}, {'text': 'mitochondrial toxicity', 'type': 'Disease', 'start': 1351, 'end': 1373, 'mesh': 'D028361'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 1407, 'end': 1417, 'mesh': 'D017239'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 1422, 'end': 1431, 'mesh': 'D002945'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 1440, 'end': 1453, 'mesh': 'D020258'}, {'text': 'Alpha-lipoic acid', 'type': 'Chemical', 'start': 1455, 'end': 1472, 'mesh': 'D008063'}, {'text': 'alpha-lipoic acid', 'type': 'Chemical', 'start': 1637, 'end': 1654, 'mesh': 'D008063'}, {'text': 'peripheral nerve toxicity', 'type': 'Disease', 'start': 1691, 'end': 1716, 'mesh': 'D010523'}]"
+368,17020434,Optimising stroke prevention in non-valvular atrial fibrillation.,"Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients.","[{'text': 'stroke', 'type': 'Disease', 'start': 11, 'end': 17, 'mesh': 'D020521'}, {'text': 'atrial fibrillation', 'type': 'Disease', 'start': 45, 'end': 64, 'mesh': 'D001281'}, {'text': 'Atrial fibrillation', 'type': 'Disease', 'start': 66, 'end': 85, 'mesh': 'D001281'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 230, 'end': 238, 'mesh': 'D014859'}, {'text': 'stroke', 'type': 'Disease', 'start': 259, 'end': 265, 'mesh': 'D020521'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 283, 'end': 290, 'mesh': 'D001241'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 354, 'end': 362, 'mesh': 'D014859'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 378, 'end': 385, 'mesh': 'D001241'}, {'text': 'strokes', 'type': 'Disease', 'start': 400, 'end': 407, 'mesh': 'D020521'}, {'text': 'Ximelagatran', 'type': 'Chemical', 'start': 448, 'end': 460, 'mesh': 'C426686'}, {'text': 'vitamin K', 'type': 'Chemical', 'start': 529, 'end': 538, 'mesh': 'D014812'}, {'text': 'embolic events', 'type': 'Disease', 'start': 577, 'end': 591, 'mesh': 'D004617'}, {'text': 'abnormal liver function', 'type': 'Disease', 'start': 636, 'end': 659, 'mesh': 'D056486'}, {'text': 'Atrial Fibrillation', 'type': 'Disease', 'start': 681, 'end': 700, 'mesh': 'D001281'}, {'text': 'Clopidogrel', 'type': 'Chemical', 'start': 701, 'end': 712, 'mesh': 'C055162'}, {'text': 'Irbesartan', 'type': 'Chemical', 'start': 724, 'end': 734, 'mesh': 'C081309'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 798, 'end': 806, 'mesh': 'D014859'}, {'text': 'clopidogrel', 'type': 'Chemical', 'start': 840, 'end': 851, 'mesh': 'C055162'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 857, 'end': 864, 'mesh': 'D001241'}, {'text': 'embolic events', 'type': 'Disease', 'start': 887, 'end': 901, 'mesh': 'D004617'}, {'text': 'Idraparinux', 'type': 'Chemical', 'start': 903, 'end': 914, 'mesh': 'C479958'}, {'text': 'atrial fibrillation', 'type': 'Disease', 'start': 975, 'end': 994, 'mesh': 'D001281'}, {'text': 'Angiotensin', 'type': 'Chemical', 'start': 996, 'end': 1007, 'mesh': 'D000809'}, {'text': 'angiotensin II', 'type': 'Chemical', 'start': 1041, 'end': 1055, 'mesh': 'D000804'}, {'text': 'atrial fibrillation', 'type': 'Disease', 'start': 1096, 'end': 1115, 'mesh': 'D001281'}, {'text': 'cardiac remodelling', 'type': 'Disease', 'start': 1124, 'end': 1143, 'mesh': 'D020257'}, {'text': 'statins', 'type': 'Chemical', 'start': 1178, 'end': 1185, 'mesh': 'D019821'}]"
+369,3865016,Interaction of cyclosporin A with antineoplastic agents.,"A synergistic effect of etoposide and cyclosporin A was observed in a patient with acute T-lymphocytic leukemia in relapse. The concomitant administration of etoposide and cyclosporin A resulted in eradication of hitherto refractory leukemic infiltration of bone marrow. Severe side effects in terms of mental confusion and progressive hyperbilirubinemia, however, point to an enhancement not only of antineoplastic effects but also of toxicity in normal tissues. This report demonstrates for the first time that the pharmacodynamic properties of cyclosporin A may not be confined strictly to suppression of normal T-cell functions.","[{'text': 'cyclosporin A', 'type': 'Chemical', 'start': 15, 'end': 28, 'mesh': 'D016572'}, {'text': 'etoposide', 'type': 'Chemical', 'start': 81, 'end': 90, 'mesh': 'D005047'}, {'text': 'cyclosporin A', 'type': 'Chemical', 'start': 95, 'end': 108, 'mesh': 'D016572'}, {'text': 'acute T-lymphocytic leukemia', 'type': 'Disease', 'start': 140, 'end': 168, 'mesh': 'D054218'}, {'text': 'etoposide', 'type': 'Chemical', 'start': 215, 'end': 224, 'mesh': 'D005047'}, {'text': 'cyclosporin A', 'type': 'Chemical', 'start': 229, 'end': 242, 'mesh': 'D016572'}, {'text': 'leukemic infiltration', 'type': 'Disease', 'start': 290, 'end': 311, 'mesh': 'D017254'}, {'text': 'confusion', 'type': 'Disease', 'start': 367, 'end': 376, 'mesh': 'D003221'}, {'text': 'hyperbilirubinemia', 'type': 'Disease', 'start': 393, 'end': 411, 'mesh': 'D006932'}, {'text': 'toxicity', 'type': 'Disease', 'start': 493, 'end': 501, 'mesh': 'D064420'}, {'text': 'cyclosporin A', 'type': 'Chemical', 'start': 604, 'end': 617, 'mesh': 'D016572'}]"
+370,3629586,The hematologic effects of cefonicid and cefazedone in the dog: a potential model of cephalosporin hematotoxicity in man.,"Cephalosporin antibiotics cause a variety of hematologic disturbances in man, the pathogeneses and hematopathology of which remain poorly characterized. There is a need for a well-defined animal model in which these blood dyscrasias can be studied. In four subacute toxicity studies, the intravenous administration of cefonicid or cefazedone to beagle dogs caused a dose-dependent incidence of anemia, neutropenia, and thrombocytopenia after 1-3 months of treatment. A nonregenerative anemia was the most compromising of the cytopenias and occurred in approximately 50% of dogs receiving 400-500 mg/kg cefonicid or 540-840 mg/kg cefazedone. All three cytopenias were completely reversible following cessation of treatment; the time required for recovery of the erythron (approximately 1 month) was considerably longer than that of the granulocytes and platelets (hours to a few days). Upon rechallenge with either cephalosporin, the hematologic syndrome was reproduced in most dogs tested; cefonicid (but not cefazedone)-treated dogs showed a substantially reduced induction period (15 +/- 5 days) compared to that of the first exposure to the drug (61 +/- 24 days). This observation, along with the rapid rate of decline in red cell mass parameters of affected dogs, suggests that a hemolytic component complicated the red cell production problem and that multiple toxicologic mechanisms contributed to the cytopenia. We conclude that the administration of high doses of cefonicid or cefazedone to dogs can induce hematotoxicity similar to the cephalosporin-induced blood dyscrasias described in man and thus provides a useful model for studying the mechanisms of these disorders.","[{'text': 'cefonicid', 'type': 'Chemical', 'start': 27, 'end': 36, 'mesh': 'D015790'}, {'text': 'cefazedone', 'type': 'Chemical', 'start': 41, 'end': 51, 'mesh': 'C021341'}, {'text': 'cephalosporin', 'type': 'Chemical', 'start': 85, 'end': 98, 'mesh': 'D002511'}, {'text': 'hematotoxicity', 'type': 'Disease', 'start': 99, 'end': 113, 'mesh': 'D006402'}, {'text': 'Cephalosporin', 'type': 'Chemical', 'start': 122, 'end': 135, 'mesh': 'D002511'}, {'text': 'hematologic disturbances', 'type': 'Disease', 'start': 167, 'end': 191, 'mesh': 'D006402'}, {'text': 'blood dyscrasias', 'type': 'Disease', 'start': 338, 'end': 354, 'mesh': 'D006402'}, {'text': 'toxicity', 'type': 'Disease', 'start': 388, 'end': 396, 'mesh': 'D064420'}, {'text': 'cefonicid', 'type': 'Chemical', 'start': 440, 'end': 449, 'mesh': 'D015790'}, {'text': 'cefazedone', 'type': 'Chemical', 'start': 453, 'end': 463, 'mesh': 'C021341'}, {'text': 'anemia', 'type': 'Disease', 'start': 516, 'end': 522, 'mesh': 'D000740'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 524, 'end': 535, 'mesh': 'D009503'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 541, 'end': 557, 'mesh': 'D013921'}, {'text': 'anemia', 'type': 'Disease', 'start': 607, 'end': 613, 'mesh': 'D000740'}, {'text': 'cytopenias', 'type': 'Disease', 'start': 647, 'end': 657, 'mesh': 'D006402'}, {'text': 'cefonicid', 'type': 'Chemical', 'start': 724, 'end': 733, 'mesh': 'D015790'}, {'text': 'cefazedone', 'type': 'Chemical', 'start': 751, 'end': 761, 'mesh': 'C021341'}, {'text': 'cytopenias', 'type': 'Disease', 'start': 773, 'end': 783, 'mesh': 'D006402'}, {'text': 'cephalosporin', 'type': 'Chemical', 'start': 1036, 'end': 1049, 'mesh': 'D002511'}, {'text': 'hematologic syndrome', 'type': 'Disease', 'start': 1055, 'end': 1075, 'mesh': 'D006402'}, {'text': 'cefonicid', 'type': 'Chemical', 'start': 1112, 'end': 1121, 'mesh': 'D015790'}, {'text': 'cefazedone', 'type': 'Chemical', 'start': 1131, 'end': 1141, 'mesh': 'C021341'}, {'text': 'hemolytic', 'type': 'Disease', 'start': 1406, 'end': 1415, 'mesh': 'D006461'}, {'text': 'cytopenia', 'type': 'Disease', 'start': 1530, 'end': 1539, 'mesh': 'D006402'}, {'text': 'cefonicid', 'type': 'Chemical', 'start': 1594, 'end': 1603, 'mesh': 'D015790'}, {'text': 'cefazedone', 'type': 'Chemical', 'start': 1607, 'end': 1617, 'mesh': 'C021341'}, {'text': 'hematotoxicity', 'type': 'Disease', 'start': 1637, 'end': 1651, 'mesh': 'D006402'}, {'text': 'cephalosporin', 'type': 'Chemical', 'start': 1667, 'end': 1680, 'mesh': 'D002511'}, {'text': 'blood dyscrasias', 'type': 'Disease', 'start': 1689, 'end': 1705, 'mesh': 'D006402'}]"
+371,150790,A pyridoxine-dependent behavioral disorder unmasked by isoniazid.,"A 3-year-old girl had behavioral deterioration, with hyperkinesis, irritability, and sleeping difficulties after the therapeutic administration of isoniazid. The administration of pharmacologic doses of pyridoxine hydrochloride led to a disappearance of symptoms. After discontinuing isoniazid therapy a similar pattern of behavior was noted that was controlled by pyridoxine. A placebo had no effect, but niacinamide was as effective as pyridoxine. Periodic withdrawal of pyridoxine was associated with return of the hyperkinesis. The level of pyridoxal in the blood was normal during the periods of relapse. Metabolic studies suggested a block in the kynurenine pathway of tryptophan metabolism. The patient has been followed for six years and has required pharmacologic doses of pyridoxine to control her behavior.","[{'text': 'pyridoxine', 'type': 'Chemical', 'start': 2, 'end': 12, 'mesh': 'D011736'}, {'text': 'behavioral disorder', 'type': 'Disease', 'start': 23, 'end': 42, 'mesh': 'D002653'}, {'text': 'isoniazid', 'type': 'Chemical', 'start': 55, 'end': 64, 'mesh': 'D007538'}, {'text': 'behavioral deterioration', 'type': 'Disease', 'start': 88, 'end': 112, 'mesh': 'D002653'}, {'text': 'hyperkinesis', 'type': 'Disease', 'start': 119, 'end': 131, 'mesh': 'D006948'}, {'text': 'irritability', 'type': 'Disease', 'start': 133, 'end': 145, 'mesh': 'D001523'}, {'text': 'sleeping difficulties', 'type': 'Disease', 'start': 151, 'end': 172, 'mesh': 'D012893'}, {'text': 'isoniazid', 'type': 'Chemical', 'start': 213, 'end': 222, 'mesh': 'D007538'}, {'text': 'pyridoxine hydrochloride', 'type': 'Chemical', 'start': 269, 'end': 293, 'mesh': 'D011736'}, {'text': 'isoniazid', 'type': 'Chemical', 'start': 350, 'end': 359, 'mesh': 'D007538'}, {'text': 'pyridoxine', 'type': 'Chemical', 'start': 431, 'end': 441, 'mesh': 'D011736'}, {'text': 'niacinamide', 'type': 'Chemical', 'start': 472, 'end': 483, 'mesh': 'D009536'}, {'text': 'pyridoxine', 'type': 'Chemical', 'start': 504, 'end': 514, 'mesh': 'D011736'}, {'text': 'pyridoxine', 'type': 'Chemical', 'start': 539, 'end': 549, 'mesh': 'D011736'}, {'text': 'hyperkinesis', 'type': 'Disease', 'start': 584, 'end': 596, 'mesh': 'D006948'}, {'text': 'pyridoxal', 'type': 'Chemical', 'start': 611, 'end': 620, 'mesh': 'D011730'}, {'text': 'kynurenine', 'type': 'Chemical', 'start': 719, 'end': 729, 'mesh': 'D007737'}, {'text': 'tryptophan', 'type': 'Chemical', 'start': 741, 'end': 751, 'mesh': 'D014364'}, {'text': 'pyridoxine', 'type': 'Chemical', 'start': 848, 'end': 858, 'mesh': 'D011736'}]"
+372,10579464,"A selective dopamine D4 receptor antagonist, NRA0160: a preclinical neuropharmacological profile.","NRA0160, 5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide, has a high affinity for human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 0.5, 0.9 and 2.7 nM, respectively. NRA0160 is over 20,000fold more potent at the dopamine D4.2 receptor compared with the human cloned dopamine D2L receptor. NRA0160 has negligible affinity for the human cloned dopamine D3 receptor (Ki=39 nM), rat serotonin (5-HT)2A receptors (Ki=180 nM) and rat alpha1 adrenoceptor (Ki=237 nM). NRA0160 and clozapine antagonized locomotor hyperactivity induced by methamphetamine (MAP) in mice. NRA0160 and clozapine antagonized MAP-induced stereotyped behavior in mice, although their effects did not exceed 50% inhibition, even at the highest dose given. NRA0160 and clozapine significantly induced catalepsy in rats, although their effects did not exceed 50% induction even at the highest dose given. NRA0160 and clozapine significantly reversed the disruption of prepulse inhibition (PPI) in rats produced by apomorphine. NRA0160 and clozapine significantly shortened the phencyclidine (PCP)-induced prolonged swimming latency in rats in a water maze task. These findings suggest that NRA0160 may have unique antipsychotic activities without the liability of motor side effects typical of classical antipsychotics.","[{'text': 'dopamine', 'type': 'Chemical', 'start': 12, 'end': 20, 'mesh': 'D004298'}, {'text': 'NRA0160', 'type': 'Chemical', 'start': 45, 'end': 52, 'mesh': 'C121249'}, {'text': 'NRA0160', 'type': 'Chemical', 'start': 98, 'end': 105, 'mesh': 'C121249'}, {'text': '5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide', 'type': 'Chemical', 'start': 107, 'end': 212, 'mesh': 'C121249'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 251, 'end': 259, 'mesh': 'D004298'}, {'text': 'NRA0160', 'type': 'Chemical', 'start': 344, 'end': 351, 'mesh': 'C121249'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 390, 'end': 398, 'mesh': 'D004298'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 444, 'end': 452, 'mesh': 'D004298'}, {'text': 'NRA0160', 'type': 'Chemical', 'start': 467, 'end': 474, 'mesh': 'C121249'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 520, 'end': 528, 'mesh': 'D004298'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 557, 'end': 566, 'mesh': 'D012701'}, {'text': '5-HT', 'type': 'Chemical', 'start': 568, 'end': 572, 'mesh': 'D012701'}, {'text': 'NRA0160', 'type': 'Chemical', 'start': 639, 'end': 646, 'mesh': 'C121249'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 651, 'end': 660, 'mesh': 'D003024'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 683, 'end': 696, 'mesh': 'D006948'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 708, 'end': 723, 'mesh': 'D008694'}, {'text': 'MAP', 'type': 'Chemical', 'start': 725, 'end': 728, 'mesh': 'D008694'}, {'text': 'NRA0160', 'type': 'Chemical', 'start': 739, 'end': 746, 'mesh': 'C121249'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 751, 'end': 760, 'mesh': 'D003024'}, {'text': 'MAP', 'type': 'Chemical', 'start': 773, 'end': 776, 'mesh': 'D008694'}, {'text': 'NRA0160', 'type': 'Chemical', 'start': 901, 'end': 908, 'mesh': 'C121249'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 913, 'end': 922, 'mesh': 'D003024'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 945, 'end': 954, 'mesh': 'D002375'}, {'text': 'NRA0160', 'type': 'Chemical', 'start': 1048, 'end': 1055, 'mesh': 'C121249'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 1060, 'end': 1069, 'mesh': 'D003024'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 1157, 'end': 1168, 'mesh': 'D001058'}, {'text': 'NRA0160', 'type': 'Chemical', 'start': 1170, 'end': 1177, 'mesh': 'C121249'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 1182, 'end': 1191, 'mesh': 'D003024'}, {'text': 'phencyclidine', 'type': 'Chemical', 'start': 1220, 'end': 1233, 'mesh': 'D010622'}, {'text': 'PCP', 'type': 'Chemical', 'start': 1235, 'end': 1238, 'mesh': 'D010622'}, {'text': 'NRA0160', 'type': 'Chemical', 'start': 1333, 'end': 1340, 'mesh': 'C121249'}]"
+373,3496378,Prolonged cholestasis after troleandomycin-induced acute hepatitis.,"We report the case of a patient in whom troleandomycin-induced hepatitis was followed by prolonged anicteric cholestasis. Jaundice occurred after administration of troleandomycin for 7 days and was associated with hypereosinophilia. Jaundice disappeared within 3 months but was followed by prolonged anicteric cholestasis marked by pruritus and high levels of alkaline phosphatase and gammaglutamyltransferase activities. Finally, pruritus disappeared within 19 months, and liver tests returned to normal 27 months after the onset of hepatitis. This observation demonstrates that prolonged cholestasis can follow troleandomycin-induced acute hepatitis.","[{'text': 'cholestasis', 'type': 'Disease', 'start': 10, 'end': 21, 'mesh': 'D002779'}, {'text': 'troleandomycin', 'type': 'Chemical', 'start': 28, 'end': 42, 'mesh': 'D014217'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 57, 'end': 66, 'mesh': 'D056486'}, {'text': 'troleandomycin', 'type': 'Chemical', 'start': 108, 'end': 122, 'mesh': 'D014217'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 131, 'end': 140, 'mesh': 'D056486'}, {'text': 'cholestasis', 'type': 'Disease', 'start': 177, 'end': 188, 'mesh': 'D002779'}, {'text': 'Jaundice', 'type': 'Disease', 'start': 190, 'end': 198, 'mesh': 'D007565'}, {'text': 'troleandomycin', 'type': 'Chemical', 'start': 232, 'end': 246, 'mesh': 'D014217'}, {'text': 'hypereosinophilia', 'type': 'Disease', 'start': 282, 'end': 299, 'mesh': 'D004802'}, {'text': 'Jaundice', 'type': 'Disease', 'start': 301, 'end': 309, 'mesh': 'D007565'}, {'text': 'cholestasis', 'type': 'Disease', 'start': 378, 'end': 389, 'mesh': 'D002779'}, {'text': 'pruritus', 'type': 'Disease', 'start': 400, 'end': 408, 'mesh': 'D011537'}, {'text': 'pruritus', 'type': 'Disease', 'start': 499, 'end': 507, 'mesh': 'D011537'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 602, 'end': 611, 'mesh': 'D056486'}, {'text': 'cholestasis', 'type': 'Disease', 'start': 658, 'end': 669, 'mesh': 'D002779'}, {'text': 'troleandomycin', 'type': 'Chemical', 'start': 681, 'end': 695, 'mesh': 'D014217'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 710, 'end': 719, 'mesh': 'D056486'}]"
+374,3076126,HMG CoA reductase inhibitors. Current clinical experience.,"Lovastatin and simvastatin are the 2 best-known members of the class of hypolipidaemic agents known as HMG CoA reductase inhibitors. Clinical experience with lovastatin includes over 5000 patients, 700 of whom have been treated for 2 years or more, and experience with simvastatin includes over 3500 patients, of whom 350 have been treated for 18 months or more. Lovastatin has been marketed in the United States for over 6 months. Both agents show substantial clinical efficacy, with reductions in total cholesterol of over 30% and in LDL-cholesterol of 40% in clinical studies. Modest increases in HDL-cholesterol levels of about 10% are also reported. Clinical tolerability of both agents has been good, with fewer than 3% of patients withdrawn from treatment because of clinical adverse experiences. Ophthalmological examinations in over 1100 patients treated with one or the other agent have revealed no evidence of significant short term (up to 2 years) cataractogenic potential. One to 2% of patients have elevations of serum transaminases to greater than 3 times the upper limit of normal. These episodes are asymptomatic and reversible when therapy is discontinued. Minor elevations of creatine kinase levels are reported in about 5% of patients. Myopathy, associated in some cases with myoglobinuria, and in 2 cases with transient renal failure, has been rarely reported with lovastatin, especially in patients concomitantly treated with cyclosporin, gemfibrozil or niacin. Lovastatin and simvastatin are both effective and well-tolerated agents for lowering elevated levels of serum cholesterol. As wider use confirms their safety profile, they will gain increasing importance in the therapeutic approach to hypercholesterolaemia and its consequences.","[{'text': 'Lovastatin', 'type': 'Chemical', 'start': 59, 'end': 69, 'mesh': 'D008148'}, {'text': 'simvastatin', 'type': 'Chemical', 'start': 74, 'end': 85, 'mesh': 'D019821'}, {'text': 'lovastatin', 'type': 'Chemical', 'start': 217, 'end': 227, 'mesh': 'D008148'}, {'text': 'simvastatin', 'type': 'Chemical', 'start': 328, 'end': 339, 'mesh': 'D019821'}, {'text': 'Lovastatin', 'type': 'Chemical', 'start': 422, 'end': 432, 'mesh': 'D008148'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 564, 'end': 575, 'mesh': 'D002784'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 599, 'end': 610, 'mesh': 'D002784'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 663, 'end': 674, 'mesh': 'D002784'}, {'text': 'creatine', 'type': 'Chemical', 'start': 1254, 'end': 1262, 'mesh': 'D003401'}, {'text': 'Myopathy', 'type': 'Disease', 'start': 1315, 'end': 1323, 'mesh': 'D009135'}, {'text': 'myoglobinuria', 'type': 'Disease', 'start': 1355, 'end': 1368, 'mesh': 'D009212'}, {'text': 'renal failure', 'type': 'Disease', 'start': 1400, 'end': 1413, 'mesh': 'D051437'}, {'text': 'lovastatin', 'type': 'Chemical', 'start': 1445, 'end': 1455, 'mesh': 'D008148'}, {'text': 'cyclosporin', 'type': 'Chemical', 'start': 1507, 'end': 1518, 'mesh': 'D016572'}, {'text': 'gemfibrozil', 'type': 'Chemical', 'start': 1520, 'end': 1531, 'mesh': 'D015248'}, {'text': 'niacin', 'type': 'Chemical', 'start': 1535, 'end': 1541, 'mesh': 'D009525'}, {'text': 'Lovastatin', 'type': 'Chemical', 'start': 1543, 'end': 1553, 'mesh': 'D008148'}, {'text': 'simvastatin', 'type': 'Chemical', 'start': 1558, 'end': 1569, 'mesh': 'D019821'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 1653, 'end': 1664, 'mesh': 'D002784'}, {'text': 'hypercholesterolaemia', 'type': 'Disease', 'start': 1778, 'end': 1799, 'mesh': 'D006937'}]"
+375,2894766,Sulfasalazine-induced lupus erythematosus.,"Pneumonitis, bilateral pleural effusions, echocardiographic evidence of cardiac tamponade, and positive autoantibodies developed in a 43-year-old man, who was receiving long-term sulfasalazine therapy for chronic ulcerative colitis. After cessation of the sulfasalazine and completion of a six-week course of corticosteroids, these problems resolved over a period of four to six months. It is suggested that the patient had sulfasalazine-induced lupus, which manifested with serositis and pulmonary parenchymal involvement in the absence of joint symptoms. Physicians who use sulfasalazine to treat patients with inflammatory bowel disease should be aware of the signs of sulfasalazine-induced lupus syndrome.","[{'text': 'Sulfasalazine', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'D012460'}, {'text': 'lupus erythematosus', 'type': 'Disease', 'start': 22, 'end': 41, 'mesh': 'D008180'}, {'text': 'Pneumonitis', 'type': 'Disease', 'start': 43, 'end': 54, 'mesh': 'D011014'}, {'text': 'pleural effusions', 'type': 'Disease', 'start': 66, 'end': 83, 'mesh': 'D010996'}, {'text': 'cardiac tamponade', 'type': 'Disease', 'start': 115, 'end': 132, 'mesh': 'D002305'}, {'text': 'sulfasalazine', 'type': 'Chemical', 'start': 222, 'end': 235, 'mesh': 'D012460'}, {'text': 'ulcerative colitis', 'type': 'Disease', 'start': 256, 'end': 274, 'mesh': 'D003093'}, {'text': 'sulfasalazine', 'type': 'Chemical', 'start': 299, 'end': 312, 'mesh': 'D012460'}, {'text': 'sulfasalazine', 'type': 'Chemical', 'start': 467, 'end': 480, 'mesh': 'D012460'}, {'text': 'lupus', 'type': 'Disease', 'start': 489, 'end': 494, 'mesh': 'D008180'}, {'text': 'serositis', 'type': 'Disease', 'start': 518, 'end': 527, 'mesh': 'D012700'}, {'text': 'sulfasalazine', 'type': 'Chemical', 'start': 619, 'end': 632, 'mesh': 'D012460'}, {'text': 'inflammatory bowel disease', 'type': 'Disease', 'start': 656, 'end': 682, 'mesh': 'D015212'}, {'text': 'sulfasalazine', 'type': 'Chemical', 'start': 715, 'end': 728, 'mesh': 'D012460'}, {'text': 'lupus syndrome', 'type': 'Disease', 'start': 737, 'end': 751, 'mesh': 'D008180'}]"
+376,1549199,Optimization of levodopa therapy.,"While there is no single correct starting dose for levodopa therapy, many individuals can be started on either the 25/100 or controlled-release formula, following the general rule not to attempt to titrate carbidopa-levodopa to the point of ""normality,"" which can lead to toxicity. The physician should also determine the proper use of any adjunctive medications; such combined therapy has become the standard approach to treatment. Following the initial period of therapy, emerging difficulties require a reassessment of therapeutic approaches, such as dosage adjustment or introduction of a dopamine agonist. Other possible adverse effects--such as gastrointestinal disorders, orthostatic hypotension, levodopa-induced psychosis, sleep disturbances or parasomnias, or drug interactions--also require carefully monitored individual treatment. Nonpharmacologic concerns can help the Parkinson's disease patient achieve and maintain optimal functioning, including daily exercise, physical therapy, and involvement with support groups.","[{'text': 'levodopa', 'type': 'Chemical', 'start': 16, 'end': 24, 'mesh': 'D007980'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 85, 'end': 93, 'mesh': 'D007980'}, {'text': 'carbidopa', 'type': 'Chemical', 'start': 240, 'end': 249, 'mesh': 'D002230'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 250, 'end': 258, 'mesh': 'D007980'}, {'text': 'toxicity', 'type': 'Disease', 'start': 306, 'end': 314, 'mesh': 'D064420'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 627, 'end': 635, 'mesh': 'D004298'}, {'text': 'gastrointestinal disorders', 'type': 'Disease', 'start': 685, 'end': 711, 'mesh': 'D005767'}, {'text': 'orthostatic hypotension', 'type': 'Disease', 'start': 713, 'end': 736, 'mesh': 'D007024'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 738, 'end': 746, 'mesh': 'D007980'}, {'text': 'psychosis', 'type': 'Disease', 'start': 755, 'end': 764, 'mesh': 'D011618'}, {'text': 'sleep disturbances', 'type': 'Disease', 'start': 766, 'end': 784, 'mesh': 'D012893'}, {'text': 'parasomnias', 'type': 'Disease', 'start': 788, 'end': 799, 'mesh': 'D020447'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 917, 'end': 936, 'mesh': 'D010300'}]"
+377,88336,Alpha and beta coma in drug intoxication uncomplicated by cerebral hypoxia.,"Four patients who were rendered comatose or stuporous by drug intoxication, but who were not hypoxic, are described. Three patients received high doses of chlormethiazole for alcohol withdrawal symptoms, and one took a suicidal overdose of nitrazepam. The patient with nitrazepam overdose and two of those with chlormethiazole intoxication conformed to the criteria of 'alpha coma', showing non-reactive generalized or frontally predominant alpha activity in the EEG. The fourth patient who was unconscious after chlormethiazole administration exhibite generalized non-reactive activity in the slow beta range. All four recovered completely without neurological sequelae following the withdrawal of the offending agents. The similarities between the effects of structural lesions and pharmacological depression of the brain stem reticular formation are discussed. It is suggested that in both situations disturbed reticulo-thalamic interactions are important in the pathogenesis of alpha coma. It is concluded that when this electroencephalographic and behavioural picture is seen in drug intoxication, in the absence of significant hypoxaemia, a favourable outcome may be anticipated.","[{'text': 'coma', 'type': 'Disease', 'start': 15, 'end': 19, 'mesh': 'D003128'}, {'text': 'cerebral hypoxia', 'type': 'Disease', 'start': 58, 'end': 74, 'mesh': 'D002534'}, {'text': 'comatose', 'type': 'Disease', 'start': 108, 'end': 116, 'mesh': 'D003128'}, {'text': 'stuporous', 'type': 'Disease', 'start': 120, 'end': 129, 'mesh': 'D053608'}, {'text': 'chlormethiazole', 'type': 'Chemical', 'start': 231, 'end': 246, 'mesh': 'D002719'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 251, 'end': 258, 'mesh': 'D000431'}, {'text': 'withdrawal symptoms', 'type': 'Disease', 'start': 259, 'end': 278, 'mesh': 'D013375'}, {'text': 'overdose', 'type': 'Disease', 'start': 304, 'end': 312, 'mesh': 'D062787'}, {'text': 'nitrazepam', 'type': 'Chemical', 'start': 316, 'end': 326, 'mesh': 'D009567'}, {'text': 'nitrazepam', 'type': 'Chemical', 'start': 345, 'end': 355, 'mesh': 'D009567'}, {'text': 'overdose', 'type': 'Disease', 'start': 356, 'end': 364, 'mesh': 'D062787'}, {'text': 'chlormethiazole', 'type': 'Chemical', 'start': 387, 'end': 402, 'mesh': 'D002719'}, {'text': 'coma', 'type': 'Disease', 'start': 452, 'end': 456, 'mesh': 'D003128'}, {'text': 'chlormethiazole', 'type': 'Chemical', 'start': 589, 'end': 604, 'mesh': 'D002719'}, {'text': 'neurological sequelae', 'type': 'Disease', 'start': 725, 'end': 746, 'mesh': 'D009422'}, {'text': 'depression', 'type': 'Disease', 'start': 876, 'end': 886, 'mesh': 'D003866'}, {'text': 'coma', 'type': 'Disease', 'start': 1064, 'end': 1068, 'mesh': 'D003128'}, {'text': 'hypoxaemia', 'type': 'Disease', 'start': 1209, 'end': 1219, 'mesh': 'D000860'}]"
+378,18544179,"Omitting fentanyl reduces nausea and vomiting, without increasing pain, after sevoflurane for day surgery.","BACKGROUND AND OBJECTIVE: Despite advantages of induction and maintenance of anaesthesia with sevoflurane, postoperative nausea and vomiting occurs frequently. Fentanyl is a commonly used supplement that may contribute to this, although it may also improve analgesia. METHODS: This double-blind study examined the incidence and severity of postoperative nausea and vomiting and pain in the first 24 h after sevoflurane anaesthesia in 216 adult day surgery patients. Patients were randomly allocated to either receive or not receive 1 1 fentanyl, while a third group received dexamethasone in addition to fentanyl. RESULTS: Omission of fentanyl did not reduce the overall incidence of postoperative nausea and vomiting, but did reduce the incidence of vomiting and/or moderate to severe nausea prior to discharge from 20% and 17% with fentanyl and fentanyl-dexamethasone, respectively, to 5% (P = 0.013). Antiemetic requirements were reduced from 24% and 31% to 7% (P = 0.0012). Dexamethasone had no significant effect on the incidence or severity of postoperative nausea and vomiting. Combining the two fentanyl groups revealed further significant benefits from the avoidance of opioids, reducing postoperative nausea and vomiting and nausea prior to discharge from 35% and 33% to 22% and 19% (P = 0.049 and P = 0.035), respectively, while nausea in the first 24 h was decreased from 42% to 27% (P = 0.034). Pain severity and analgesic requirements were unaffected by the omission of fentanyl. Fentanyl did reduce minor intraoperative movement but had no sevoflurane-sparing effect and increased respiratory depression, hypotension and bradycardia. CONCLUSION: As fentanyl exacerbated postoperative nausea and vomiting without an improvement in postoperative pain and also had adverse cardiorespiratory effects, it appears to be an unnecessary and possibly detrimental supplement to sevoflurane in day surgery.","[{'text': 'fentanyl', 'type': 'Chemical', 'start': 9, 'end': 17, 'mesh': 'D005283'}, {'text': 'nausea', 'type': 'Disease', 'start': 26, 'end': 32, 'mesh': 'D009325'}, {'text': 'vomiting', 'type': 'Disease', 'start': 37, 'end': 45, 'mesh': 'D014839'}, {'text': 'pain', 'type': 'Disease', 'start': 66, 'end': 70, 'mesh': 'D010146'}, {'text': 'sevoflurane', 'type': 'Chemical', 'start': 78, 'end': 89, 'mesh': 'C009250'}, {'text': 'sevoflurane', 'type': 'Chemical', 'start': 201, 'end': 212, 'mesh': 'C009250'}, {'text': 'postoperative nausea and vomiting', 'type': 'Disease', 'start': 214, 'end': 247, 'mesh': 'D020250'}, {'text': 'Fentanyl', 'type': 'Chemical', 'start': 267, 'end': 275, 'mesh': 'D005283'}, {'text': 'postoperative nausea and vomiting', 'type': 'Disease', 'start': 447, 'end': 480, 'mesh': 'D020250'}, {'text': 'pain', 'type': 'Disease', 'start': 485, 'end': 489, 'mesh': 'D010146'}, {'text': 'sevoflurane', 'type': 'Chemical', 'start': 514, 'end': 525, 'mesh': 'C009250'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 643, 'end': 651, 'mesh': 'D005283'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 682, 'end': 695, 'mesh': 'D003907'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 711, 'end': 719, 'mesh': 'D005283'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 742, 'end': 750, 'mesh': 'D005283'}, {'text': 'postoperative nausea and vomiting', 'type': 'Disease', 'start': 791, 'end': 824, 'mesh': 'D020250'}, {'text': 'vomiting', 'type': 'Disease', 'start': 858, 'end': 866, 'mesh': 'D014839'}, {'text': 'nausea', 'type': 'Disease', 'start': 893, 'end': 899, 'mesh': 'D009325'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 941, 'end': 949, 'mesh': 'D005283'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 954, 'end': 962, 'mesh': 'D005283'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 963, 'end': 976, 'mesh': 'D003907'}, {'text': 'Dexamethasone', 'type': 'Chemical', 'start': 1085, 'end': 1098, 'mesh': 'D003907'}, {'text': 'postoperative nausea and vomiting', 'type': 'Disease', 'start': 1157, 'end': 1190, 'mesh': 'D020250'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 1210, 'end': 1218, 'mesh': 'D005283'}, {'text': 'postoperative nausea and vomiting', 'type': 'Disease', 'start': 1304, 'end': 1337, 'mesh': 'D020250'}, {'text': 'nausea', 'type': 'Disease', 'start': 1342, 'end': 1348, 'mesh': 'D009325'}, {'text': 'nausea', 'type': 'Disease', 'start': 1447, 'end': 1453, 'mesh': 'D009325'}, {'text': 'Pain', 'type': 'Disease', 'start': 1515, 'end': 1519, 'mesh': 'D010146'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 1591, 'end': 1599, 'mesh': 'D005283'}, {'text': 'Fentanyl', 'type': 'Chemical', 'start': 1601, 'end': 1609, 'mesh': 'D005283'}, {'text': 'sevoflurane', 'type': 'Chemical', 'start': 1662, 'end': 1673, 'mesh': 'C009250'}, {'text': 'respiratory depression', 'type': 'Disease', 'start': 1703, 'end': 1725, 'mesh': 'D012131'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1727, 'end': 1738, 'mesh': 'D007022'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 1743, 'end': 1754, 'mesh': 'D001919'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 1771, 'end': 1779, 'mesh': 'D005283'}, {'text': 'postoperative nausea and vomiting', 'type': 'Disease', 'start': 1792, 'end': 1825, 'mesh': 'D020250'}, {'text': 'postoperative pain', 'type': 'Disease', 'start': 1852, 'end': 1870, 'mesh': 'D010149'}, {'text': 'sevoflurane', 'type': 'Chemical', 'start': 1990, 'end': 2001, 'mesh': 'C009250'}]"
+379,18186898,Renal Fanconi syndrome and myopathy after liver transplantation: drug-related mitochondrial cytopathy?,"Advances in the field of transplantation provide a better quality of life and allow more favorable conditions for growth and development in children. However, combinations of different therapeutic regimens require consideration of potential adverse reactions. We describe a 15-yr-old girl who had orthotopic liver transplantation because of Wilson's disease. Tacrolimus, MMF, and steroids were given as immunosuppressant. Lamivudine was added because of de nova hepatitis B infection during her follow-up. Three yr after transplantation she developed renal Fanconi syndrome with severe metabolic acidosis, hypophosphatemia, glycosuria, and aminoaciduria. Although tacrolimus was suspected to be the cause of late post-transplant renal acidosis and was replaced by sirolimus, acidosis, and electrolyte imbalance got worse. Proximal muscle weakness has developed during her follow-up. Fanconi syndrome, as well as myopathy, is well recognized in patients with mitochondrial disorders and caused by depletion of mtDNA. We suggest that our patient's tubular dysfunction and myopathy may have resulted from mitochondrial dysfunction which is triggered by tacrolimus and augmented by lamivudine.","[{'text': 'Renal Fanconi syndrome', 'type': 'Disease', 'start': 0, 'end': 22, 'mesh': 'D005198'}, {'text': 'myopathy', 'type': 'Disease', 'start': 27, 'end': 35, 'mesh': 'D009135'}, {'text': 'mitochondrial cytopathy', 'type': 'Disease', 'start': 78, 'end': 101, 'mesh': 'C540770'}, {'text': ""Wilson's disease"", 'type': 'Disease', 'start': 444, 'end': 460, 'mesh': 'D006527'}, {'text': 'Tacrolimus', 'type': 'Chemical', 'start': 462, 'end': 472, 'mesh': 'D016559'}, {'text': 'MMF', 'type': 'Chemical', 'start': 474, 'end': 477, 'mesh': '-1'}, {'text': 'steroids', 'type': 'Chemical', 'start': 483, 'end': 491, 'mesh': 'D013256'}, {'text': 'Lamivudine', 'type': 'Chemical', 'start': 525, 'end': 535, 'mesh': 'D019259'}, {'text': 'hepatitis B infection', 'type': 'Disease', 'start': 565, 'end': 586, 'mesh': 'D006509'}, {'text': 'renal Fanconi syndrome', 'type': 'Disease', 'start': 654, 'end': 676, 'mesh': 'D005198'}, {'text': 'metabolic acidosis', 'type': 'Disease', 'start': 689, 'end': 707, 'mesh': 'D000138'}, {'text': 'hypophosphatemia', 'type': 'Disease', 'start': 709, 'end': 725, 'mesh': 'D017674'}, {'text': 'glycosuria', 'type': 'Disease', 'start': 727, 'end': 737, 'mesh': 'D006029'}, {'text': 'aminoaciduria', 'type': 'Disease', 'start': 743, 'end': 756, 'mesh': 'D000608'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 767, 'end': 777, 'mesh': 'D016559'}, {'text': 'acidosis', 'type': 'Disease', 'start': 838, 'end': 846, 'mesh': 'D000138'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 867, 'end': 876, 'mesh': 'D020123'}, {'text': 'acidosis', 'type': 'Disease', 'start': 878, 'end': 886, 'mesh': 'D000138'}, {'text': 'muscle weakness', 'type': 'Disease', 'start': 934, 'end': 949, 'mesh': 'D018908'}, {'text': 'Fanconi syndrome', 'type': 'Disease', 'start': 986, 'end': 1002, 'mesh': 'D005198'}, {'text': 'myopathy', 'type': 'Disease', 'start': 1015, 'end': 1023, 'mesh': 'D009135'}, {'text': 'mitochondrial disorders', 'type': 'Disease', 'start': 1061, 'end': 1084, 'mesh': 'D028361'}, {'text': 'tubular dysfunction', 'type': 'Disease', 'start': 1149, 'end': 1168, 'mesh': 'D005198'}, {'text': 'myopathy', 'type': 'Disease', 'start': 1173, 'end': 1181, 'mesh': 'D009135'}, {'text': 'mitochondrial dysfunction', 'type': 'Disease', 'start': 1205, 'end': 1230, 'mesh': 'D028361'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 1253, 'end': 1263, 'mesh': 'D016559'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 1281, 'end': 1291, 'mesh': 'D019259'}]"
+380,16867021,"Antipsychotic-like profile of thioperamide, a selective H3-receptor antagonist in mice.","Experimental and clinical evidence points to a role of central histaminergic system in the pathogenesis of schizophrenia. The present study was designed to study the effect of histamine H(3)-receptor ligands on neuroleptic-induced catalepsy, apomorphine-induced climbing behavior and amphetamine-induced locomotor activities in mice. Catalepsy was induced by haloperidol (2 mg/kg p.o.), while apomorphine (1.5 mg/kg s.c.) and amphetamine (2 mg/kg s.c.) were used for studying climbing behavior and locomotor activities, respectively. (R)-alpha-methylhistamine (RAMH) (5 microg i.c.v.) and thioperamide (THP) (15 mg/kg i.p.), per se did not cause catalepsy. Administration of THP (3.75, 7.5 and 15 mg/kg i.p.) 1 h prior to haloperidol resulted in a dose-dependent increase in the catalepsy times (P < 0.05). However, pretreatment with RAMH significantly reversed such an effect of THP (15 mg/kg i.p.). RAMH per se showed significant reduction in locomotor time, distance traveled and average speed but THP (15 mg/kg i.p.) per se had no effect on these parameters. On amphetamine-induced hyperactivity, THP (3.75 and 7.5 mg/kg i.p.) reduced locomotor time, distance traveled and average speed (P < 0.05). Pretreatment with RAMH (5 microg i.c.v.) could partially reverse such effects of THP (3.75 mg/kg i.p.). Climbing behavior induced by apomorphine was reduced in animals treated with THP. Such an effect was, however, reversed in presence of RAMH. THP exhibited an antipsychotic-like profile by potentiating haloperidol-induced catalepsy, reducing amphetamine-induced hyperactivity and reducing apomorphine-induced climbing in mice. Such effects of THP were reversed by RAMH indicating the involvement of histamine H(3)-receptors. Findings suggest a potential for H(3)-receptor antagonists in improving the refractory cases of schizophrenia.","[{'text': 'thioperamide', 'type': 'Chemical', 'start': 30, 'end': 42, 'mesh': 'C052075'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 195, 'end': 208, 'mesh': 'D012559'}, {'text': 'histamine', 'type': 'Chemical', 'start': 264, 'end': 273, 'mesh': 'D006632'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 319, 'end': 328, 'mesh': 'D002375'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 330, 'end': 341, 'mesh': 'D001058'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 372, 'end': 383, 'mesh': 'D000661'}, {'text': 'Catalepsy', 'type': 'Disease', 'start': 422, 'end': 431, 'mesh': 'D002375'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 447, 'end': 458, 'mesh': 'D006220'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 481, 'end': 492, 'mesh': 'D001058'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 514, 'end': 525, 'mesh': 'D000661'}, {'text': '(R)-alpha-methylhistamine', 'type': 'Chemical', 'start': 622, 'end': 647, 'mesh': 'C069357'}, {'text': 'RAMH', 'type': 'Chemical', 'start': 649, 'end': 653, 'mesh': 'C069357'}, {'text': 'thioperamide', 'type': 'Chemical', 'start': 677, 'end': 689, 'mesh': 'C052075'}, {'text': 'THP', 'type': 'Chemical', 'start': 691, 'end': 694, 'mesh': 'C052075'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 734, 'end': 743, 'mesh': 'D002375'}, {'text': 'THP', 'type': 'Chemical', 'start': 763, 'end': 766, 'mesh': 'C052075'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 810, 'end': 821, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 867, 'end': 876, 'mesh': 'D002375'}, {'text': 'RAMH', 'type': 'Chemical', 'start': 922, 'end': 926, 'mesh': 'C069357'}, {'text': 'THP', 'type': 'Chemical', 'start': 968, 'end': 971, 'mesh': 'C052075'}, {'text': 'RAMH', 'type': 'Chemical', 'start': 989, 'end': 993, 'mesh': 'C069357'}, {'text': 'THP', 'type': 'Chemical', 'start': 1089, 'end': 1092, 'mesh': 'C052075'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1154, 'end': 1165, 'mesh': 'D000661'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 1174, 'end': 1187, 'mesh': 'D006948'}, {'text': 'THP', 'type': 'Chemical', 'start': 1189, 'end': 1192, 'mesh': 'C052075'}, {'text': 'RAMH', 'type': 'Chemical', 'start': 1309, 'end': 1313, 'mesh': 'C069357'}, {'text': 'THP', 'type': 'Chemical', 'start': 1372, 'end': 1375, 'mesh': 'C052075'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 1424, 'end': 1435, 'mesh': 'D001058'}, {'text': 'THP', 'type': 'Chemical', 'start': 1472, 'end': 1475, 'mesh': 'C052075'}, {'text': 'RAMH', 'type': 'Chemical', 'start': 1530, 'end': 1534, 'mesh': 'C069357'}, {'text': 'THP', 'type': 'Chemical', 'start': 1536, 'end': 1539, 'mesh': 'C052075'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1596, 'end': 1607, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 1616, 'end': 1625, 'mesh': 'D002375'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1636, 'end': 1647, 'mesh': 'D000661'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 1656, 'end': 1669, 'mesh': 'D006948'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 1683, 'end': 1694, 'mesh': 'D001058'}, {'text': 'THP', 'type': 'Chemical', 'start': 1737, 'end': 1740, 'mesh': 'C052075'}, {'text': 'RAMH', 'type': 'Chemical', 'start': 1758, 'end': 1762, 'mesh': 'C069357'}, {'text': 'histamine', 'type': 'Chemical', 'start': 1793, 'end': 1802, 'mesh': 'D006632'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 1915, 'end': 1928, 'mesh': 'D012559'}]"
+381,14976857,Transient platypnea-orthodeoxia-like syndrome induced by propafenone overdose in a young woman with Ebstein's anomaly.,"In this report we describe the case of a 37-year-old white woman with Ebstein's anomaly, who developed a rare syndrome called platypnea-orthodeoxia, characterized by massive right-to-left interatrial shunting with transient profound hypoxia and cyanosis. This shunt of blood via a patent foramen ovale occurred in the presence of a normal pulmonary artery pressure, and was probably precipitated by a propafenone overdose. This drug caused biventricular dysfunction, due to its negative inotropic effect, and hypotension, due to its peripheral vasodilatory effect. These effects gave rise to an increase in the right atrial pressure and a decrease in the left one with a consequent stretching of the foramen ovale and the creation of massive right-to-left shunting. In our case this interatrial shunt was very accurately detected at bubble contrast echocardiography.","[{'text': 'platypnea-orthodeoxia-like syndrome', 'type': 'Disease', 'start': 10, 'end': 45, 'mesh': '-1'}, {'text': 'propafenone', 'type': 'Chemical', 'start': 57, 'end': 68, 'mesh': 'D011405'}, {'text': 'overdose', 'type': 'Disease', 'start': 69, 'end': 77, 'mesh': 'D062787'}, {'text': ""Ebstein's anomaly"", 'type': 'Disease', 'start': 100, 'end': 117, 'mesh': 'D004437'}, {'text': ""Ebstein's anomaly"", 'type': 'Disease', 'start': 189, 'end': 206, 'mesh': 'D004437'}, {'text': 'platypnea-orthodeoxia', 'type': 'Disease', 'start': 245, 'end': 266, 'mesh': '-1'}, {'text': 'hypoxia', 'type': 'Disease', 'start': 352, 'end': 359, 'mesh': 'D000860'}, {'text': 'cyanosis', 'type': 'Disease', 'start': 364, 'end': 372, 'mesh': 'D003490'}, {'text': 'patent foramen ovale', 'type': 'Disease', 'start': 400, 'end': 420, 'mesh': 'D054092'}, {'text': 'propafenone', 'type': 'Chemical', 'start': 520, 'end': 531, 'mesh': 'D011405'}, {'text': 'overdose', 'type': 'Disease', 'start': 532, 'end': 540, 'mesh': 'D062787'}, {'text': 'biventricular dysfunction', 'type': 'Disease', 'start': 559, 'end': 584, 'mesh': 'D018754'}, {'text': 'hypotension', 'type': 'Disease', 'start': 628, 'end': 639, 'mesh': 'D007022'}]"
+382,11745184,A Phase II trial of cisplatin plus WR-2721 (amifostine) for metastatic breast carcinoma: an Eastern Cooperative Oncology Group Study (E8188).,"BACKGROUND: Cisplatin has minimal antitumor activity when used as second- or third-line treatment of metastatic breast carcinoma. Older reports suggest an objective response rate of 8% when 60-120 mg/m2 of cisplatin is administered every 3-4 weeks. Although a dose-response effect has been observed with cisplatin, the dose-limiting toxicities associated with cisplatin (e.g., nephrotoxicity, ototoxicity, and neurotoxicity) have limited its use as a treatment for breast carcinoma. WR-2721 or amifostine initially was developed to protect military personnel in the event of nuclear war. Amifostine subsequently was shown to protect normal tissues from the toxic effects of alkylating agents and cisplatin without decreasing the antitumor effect of the chemotherapy. Early trials of cisplatin and amifostine also suggested that the incidence and severity of cisplatin-induced nephrotoxicity, ototoxicity, and neuropathy were reduced. METHODS: A Phase II study of the combination of cisplatin plus amifostine was conducted in patients with progressive metastatic breast carcinoma who had received one, but not more than one, chemotherapy regimen for metastatic disease. Patients received amifostine, 910 mg/m2 intravenously over 15 minutes. After completion of the amifostine infusion, cisplatin 120 mg/m2 was administered over 30 minutes. Intravenous hydration and mannitol was administered before and after cisplatin. Treatment was administered every 3 weeks until disease progression. RESULTS: Forty-four patients were enrolled in the study of which 7 (16%) were ineligible. A median of 2 cycles of therapy was administered to the 37 eligible patients. Six partial responses were observed for an overall response rate of 16%. Most patients (57%) stopped treatment because of disease progression. Neurologic toxicity was reported in 52% of patients. Seven different life-threatening toxicities were observed in patients while receiving treatment. CONCLUSIONS: The combination of cisplatin and amifostine in this study resulted in an overall response rate of 16%. Neither a tumor-protective effect nor reduced toxicity to normal tissues was observed with the addition of amifostine to cisplatin in this trial.","[{'text': 'cisplatin', 'type': 'Chemical', 'start': 20, 'end': 29, 'mesh': 'D002945'}, {'text': 'WR-2721', 'type': 'Chemical', 'start': 35, 'end': 42, 'mesh': 'D004999'}, {'text': 'amifostine', 'type': 'Chemical', 'start': 44, 'end': 54, 'mesh': 'D004999'}, {'text': 'breast carcinoma', 'type': 'Disease', 'start': 71, 'end': 87, 'mesh': 'D001943'}, {'text': 'Cisplatin', 'type': 'Chemical', 'start': 154, 'end': 163, 'mesh': 'D002945'}, {'text': 'breast carcinoma', 'type': 'Disease', 'start': 254, 'end': 270, 'mesh': 'D001943'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 348, 'end': 357, 'mesh': 'D002945'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 446, 'end': 455, 'mesh': 'D002945'}, {'text': 'toxicities', 'type': 'Disease', 'start': 475, 'end': 485, 'mesh': 'D064420'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 502, 'end': 511, 'mesh': 'D002945'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 519, 'end': 533, 'mesh': 'D007674'}, {'text': 'ototoxicity', 'type': 'Disease', 'start': 535, 'end': 546, 'mesh': 'D006311'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 552, 'end': 565, 'mesh': 'D020258'}, {'text': 'breast carcinoma', 'type': 'Disease', 'start': 607, 'end': 623, 'mesh': 'D001943'}, {'text': 'WR-2721', 'type': 'Chemical', 'start': 625, 'end': 632, 'mesh': 'D004999'}, {'text': 'amifostine', 'type': 'Chemical', 'start': 636, 'end': 646, 'mesh': 'D004999'}, {'text': 'Amifostine', 'type': 'Chemical', 'start': 730, 'end': 740, 'mesh': 'D004999'}, {'text': 'alkylating agents', 'type': 'Chemical', 'start': 816, 'end': 833, 'mesh': 'D000477'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 838, 'end': 847, 'mesh': 'D002945'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 925, 'end': 934, 'mesh': 'D002945'}, {'text': 'amifostine', 'type': 'Chemical', 'start': 939, 'end': 949, 'mesh': 'D004999'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 1000, 'end': 1009, 'mesh': 'D002945'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1018, 'end': 1032, 'mesh': 'D007674'}, {'text': 'ototoxicity', 'type': 'Disease', 'start': 1034, 'end': 1045, 'mesh': 'D006311'}, {'text': 'neuropathy', 'type': 'Disease', 'start': 1051, 'end': 1061, 'mesh': 'D009422'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 1124, 'end': 1133, 'mesh': 'D002945'}, {'text': 'amifostine', 'type': 'Chemical', 'start': 1139, 'end': 1149, 'mesh': 'D004999'}, {'text': 'breast carcinoma', 'type': 'Disease', 'start': 1204, 'end': 1220, 'mesh': 'D001943'}, {'text': 'amifostine', 'type': 'Chemical', 'start': 1329, 'end': 1339, 'mesh': 'D004999'}, {'text': 'amifostine', 'type': 'Chemical', 'start': 1406, 'end': 1416, 'mesh': 'D004999'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 1427, 'end': 1436, 'mesh': 'D002945'}, {'text': 'mannitol', 'type': 'Chemical', 'start': 1507, 'end': 1515, 'mesh': 'D008353'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 1550, 'end': 1559, 'mesh': 'D002945'}, {'text': 'Neurologic toxicity', 'type': 'Disease', 'start': 1940, 'end': 1959, 'mesh': 'D020258'}, {'text': 'toxicities', 'type': 'Disease', 'start': 2026, 'end': 2036, 'mesh': 'D064420'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 2122, 'end': 2131, 'mesh': 'D002945'}, {'text': 'amifostine', 'type': 'Chemical', 'start': 2136, 'end': 2146, 'mesh': 'D004999'}, {'text': 'tumor', 'type': 'Disease', 'start': 2216, 'end': 2221, 'mesh': 'D009369'}, {'text': 'toxicity', 'type': 'Disease', 'start': 2252, 'end': 2260, 'mesh': 'D064420'}, {'text': 'amifostine', 'type': 'Chemical', 'start': 2313, 'end': 2323, 'mesh': 'D004999'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 2327, 'end': 2336, 'mesh': 'D002945'}]"
+383,3985451,Warfarin-induced iliopsoas hemorrhage with subsequent femoral nerve palsy.,"We present the case of a 28-year-old man on chronic warfarin therapy who sustained a minor muscle tear and developed increasing pain and a flexure contracture of the right hip. Surgical exploration revealed an iliopsoas hematoma and femoral nerve entrapment, resulting in a femoral nerve palsy and partial loss of quadriceps functions. Anticoagulant-induced femoral nerve palsy represents the most common form of warfarin-induced peripheral neuropathy; it is characterized by severe pain in the inguinal region, varying degrees of motor and sensory impairment, and flexure contracture of the involved extremity.","[{'text': 'Warfarin', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D014859'}, {'text': 'hemorrhage', 'type': 'Disease', 'start': 27, 'end': 37, 'mesh': 'D006470'}, {'text': 'femoral nerve palsy', 'type': 'Disease', 'start': 54, 'end': 73, 'mesh': 'D020428'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 127, 'end': 135, 'mesh': 'D014859'}, {'text': 'muscle tear', 'type': 'Disease', 'start': 166, 'end': 177, 'mesh': 'D009135'}, {'text': 'pain', 'type': 'Disease', 'start': 203, 'end': 207, 'mesh': 'D010146'}, {'text': 'contracture', 'type': 'Disease', 'start': 222, 'end': 233, 'mesh': 'D003286'}, {'text': 'hematoma', 'type': 'Disease', 'start': 295, 'end': 303, 'mesh': 'D006406'}, {'text': 'nerve entrapment', 'type': 'Disease', 'start': 316, 'end': 332, 'mesh': 'D009408'}, {'text': 'femoral nerve palsy', 'type': 'Disease', 'start': 349, 'end': 368, 'mesh': 'D020428'}, {'text': 'partial loss of quadriceps functions', 'type': 'Disease', 'start': 373, 'end': 409, 'mesh': 'D009135'}, {'text': 'femoral nerve palsy', 'type': 'Disease', 'start': 433, 'end': 452, 'mesh': 'D020428'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 488, 'end': 496, 'mesh': 'D014859'}, {'text': 'peripheral neuropathy', 'type': 'Disease', 'start': 505, 'end': 526, 'mesh': 'D010523'}, {'text': 'pain', 'type': 'Disease', 'start': 558, 'end': 562, 'mesh': 'D010146'}, {'text': 'motor and sensory impairment', 'type': 'Disease', 'start': 606, 'end': 634, 'mesh': 'D015417'}, {'text': 'contracture', 'type': 'Disease', 'start': 648, 'end': 659, 'mesh': 'D003286'}]"
+384,3750012,Myasthenia gravis caused by penicillamine and chloroquine therapy for rheumatoid arthritis.,"We have described a unique patient who had reversible and dose-related myasthenia gravis after penicillamine and chloroquine therapy for rheumatoid arthritis. Although acetylcholine receptor antibodies were not detectable, the time course was consistent with an autoimmune process.","[{'text': 'Myasthenia gravis', 'type': 'Disease', 'start': 0, 'end': 17, 'mesh': 'D009157'}, {'text': 'penicillamine', 'type': 'Chemical', 'start': 28, 'end': 41, 'mesh': 'D010396'}, {'text': 'chloroquine', 'type': 'Chemical', 'start': 46, 'end': 57, 'mesh': 'D002738'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 70, 'end': 90, 'mesh': 'D001172'}, {'text': 'myasthenia gravis', 'type': 'Disease', 'start': 163, 'end': 180, 'mesh': 'D009157'}, {'text': 'penicillamine', 'type': 'Chemical', 'start': 187, 'end': 200, 'mesh': 'D010396'}, {'text': 'chloroquine', 'type': 'Chemical', 'start': 205, 'end': 216, 'mesh': 'D002738'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 229, 'end': 249, 'mesh': 'D001172'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 260, 'end': 273, 'mesh': 'D000109'}]"
+385,1130930,Nephrotoxicity of combined cephalothin-gentamicin regimen.,"Two patients developed acute tubular necrosis, characterized clinically by acute oliguric renal failure, while they were receiving a combination of cephalothin sodium and gentamicin sulfate therapy. Patients who are given this drug regimen should be observed very carefully for early signs of nephrotoxicity. High doses of this antibiotic combination should be avoided especially in elderly patients. Patients with renal insufficiency should not be given this regimen.","[{'text': 'Nephrotoxicity', 'type': 'Disease', 'start': 0, 'end': 14, 'mesh': 'D007674'}, {'text': 'cephalothin', 'type': 'Chemical', 'start': 27, 'end': 38, 'mesh': 'D002512'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 39, 'end': 49, 'mesh': 'D005839'}, {'text': 'acute tubular necrosis', 'type': 'Disease', 'start': 82, 'end': 104, 'mesh': 'D007683'}, {'text': 'cephalothin sodium', 'type': 'Chemical', 'start': 207, 'end': 225, 'mesh': 'D002512'}, {'text': 'gentamicin sulfate', 'type': 'Chemical', 'start': 230, 'end': 248, 'mesh': 'D005839'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 352, 'end': 366, 'mesh': 'D007674'}, {'text': 'renal insufficiency', 'type': 'Disease', 'start': 474, 'end': 493, 'mesh': 'D051437'}]"
+386,19356307,Components of lemon essential oil attenuate dementia induced by scopolamine.,"The anti-dementia effects of s-limonene and s-perillyl alcohol were observed using the passive avoidance test (PA) and the open field habituation test (OFH). These lemon essential oils showed strong ability to improve memory impaired by scopolamine; however, s-perillyl alcohol relieved the deficit of associative memory in PA only, and did not improve non-associative memory significantly in OFH. Analysis of neurotransmitter concentration in some brain regions on the test day showed that dopamine concentration of the vehicle/scopolamine group was significantly lower than that of the vehicle/vehicle group, but this phenomenon was reversed when s-limonene or s-perillyl alcohol were administered before the injection of scopolamine. Simultaneously, we found that these two lemon essential oil components could inhibit acetylcholinesterase activity in vitro using the Ellman method.","[{'text': 'dementia', 'type': 'Disease', 'start': 44, 'end': 52, 'mesh': 'D003704'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 64, 'end': 75, 'mesh': 'D012601'}, {'text': 'dementia', 'type': 'Disease', 'start': 86, 'end': 94, 'mesh': 'D003704'}, {'text': 's-limonene', 'type': 'Chemical', 'start': 106, 'end': 116, 'mesh': 'C008281'}, {'text': 's-perillyl alcohol', 'type': 'Chemical', 'start': 121, 'end': 139, 'mesh': 'C032208'}, {'text': 'memory impaired', 'type': 'Disease', 'start': 295, 'end': 310, 'mesh': 'D008569'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 314, 'end': 325, 'mesh': 'D012601'}, {'text': 's-perillyl alcohol', 'type': 'Chemical', 'start': 336, 'end': 354, 'mesh': 'C032208'}, {'text': 'deficit of associative memory', 'type': 'Disease', 'start': 368, 'end': 397, 'mesh': 'D008569'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 568, 'end': 576, 'mesh': 'D004298'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 606, 'end': 617, 'mesh': 'D012601'}, {'text': 's-limonene', 'type': 'Chemical', 'start': 726, 'end': 736, 'mesh': 'C008281'}, {'text': 's-perillyl alcohol', 'type': 'Chemical', 'start': 740, 'end': 758, 'mesh': 'C032208'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 801, 'end': 812, 'mesh': 'D012601'}]"
+387,15957009,The selective 5-HT6 receptor antagonist Ro4368554 restores memory performance in cholinergic and serotonergic models of memory deficiency in the rat.,"Antagonists at serotonin type 6 (5-HT(6)) receptors show activity in models of learning and memory. Although the underlying mechanism(s) are not well understood, these effects may involve an increase in acetylcholine (ACh) levels. The present study sought to characterize the cognitive-enhancing effects of the 5-HT(6) antagonist Ro4368554 (3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole) in a rat object recognition task employing a cholinergic (scopolamine pretreatment) and a serotonergic- (tryptophan (TRP) depletion) deficient model, and compared its pattern of action with that of the acetylcholinesterase inhibitor metrifonate. Initial testing in a time-dependent forgetting task employing a 24-h delay between training and testing showed that metrifonate improved object recognition (at 10 and 30 mg/kg, p.o.), whereas Ro4368554 was inactive. Both, Ro4368554 (3 and 10 mg/kg, intraperitoneally (i.p.)) and metrifonate (10 mg/kg, p.o., respectively) reversed memory deficits induced by scopolamine and TRP depletion (10 mg/kg, i.p., and 3 mg/kg, p.o., respectively). In conclusion, although Ro4368554 did not improve a time-related retention deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting that both mechanisms may be involved in the facilitation of object memory by Ro4368554 and, possibly, other 5-HT(6) receptor antagonists.","[{'text': 'Ro4368554', 'type': 'Chemical', 'start': 40, 'end': 49, 'mesh': 'C507242'}, {'text': 'memory deficiency', 'type': 'Disease', 'start': 120, 'end': 137, 'mesh': 'D008569'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 165, 'end': 174, 'mesh': 'D012701'}, {'text': '5-HT', 'type': 'Chemical', 'start': 183, 'end': 187, 'mesh': 'D012701'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 353, 'end': 366, 'mesh': 'D000109'}, {'text': 'ACh', 'type': 'Chemical', 'start': 368, 'end': 371, 'mesh': 'D000109'}, {'text': '5-HT', 'type': 'Chemical', 'start': 461, 'end': 465, 'mesh': 'D012701'}, {'text': 'Ro4368554', 'type': 'Chemical', 'start': 480, 'end': 489, 'mesh': 'C507242'}, {'text': '3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole', 'type': 'Chemical', 'start': 491, 'end': 545, 'mesh': 'C507242'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 605, 'end': 616, 'mesh': 'D012601'}, {'text': 'tryptophan', 'type': 'Chemical', 'start': 652, 'end': 662, 'mesh': 'D014364'}, {'text': 'TRP', 'type': 'Chemical', 'start': 664, 'end': 667, 'mesh': 'D014364'}, {'text': 'metrifonate', 'type': 'Chemical', 'start': 780, 'end': 791, 'mesh': 'D014236'}, {'text': 'metrifonate', 'type': 'Chemical', 'start': 909, 'end': 920, 'mesh': 'D014236'}, {'text': 'Ro4368554', 'type': 'Chemical', 'start': 985, 'end': 994, 'mesh': 'C507242'}, {'text': 'Ro4368554', 'type': 'Chemical', 'start': 1015, 'end': 1024, 'mesh': 'C507242'}, {'text': 'metrifonate', 'type': 'Chemical', 'start': 1072, 'end': 1083, 'mesh': 'D014236'}, {'text': 'memory deficits', 'type': 'Disease', 'start': 1124, 'end': 1139, 'mesh': 'D008569'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 1151, 'end': 1162, 'mesh': 'D012601'}, {'text': 'TRP', 'type': 'Chemical', 'start': 1167, 'end': 1170, 'mesh': 'D014364'}, {'text': 'Ro4368554', 'type': 'Chemical', 'start': 1256, 'end': 1265, 'mesh': 'C507242'}, {'text': 'memory deficit', 'type': 'Disease', 'start': 1361, 'end': 1375, 'mesh': 'D008569'}, {'text': 'Ro4368554', 'type': 'Chemical', 'start': 1465, 'end': 1474, 'mesh': 'C507242'}, {'text': '5-HT', 'type': 'Chemical', 'start': 1496, 'end': 1500, 'mesh': 'D012701'}]"
+388,15899738,Lone atrial fibrillation associated with creatine monohydrate supplementation.,"Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature.","[{'text': 'atrial fibrillation', 'type': 'Disease', 'start': 5, 'end': 24, 'mesh': 'D001281'}, {'text': 'creatine', 'type': 'Chemical', 'start': 41, 'end': 49, 'mesh': 'D003401'}, {'text': 'Atrial fibrillation', 'type': 'Disease', 'start': 79, 'end': 98, 'mesh': 'D001281'}, {'text': 'heart disease', 'type': 'Disease', 'start': 136, 'end': 149, 'mesh': 'D006331'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 179, 'end': 189, 'mesh': 'D001145'}, {'text': 'Thyroid disorders', 'type': 'Disease', 'start': 272, 'end': 289, 'mesh': 'D013959'}, {'text': 'acute alcohol intoxication', 'type': 'Disease', 'start': 326, 'end': 352, 'mesh': 'D000435'}, {'text': 'atrial fibrillation', 'type': 'Disease', 'start': 467, 'end': 486, 'mesh': 'D001281'}, {'text': 'fractures', 'type': 'Disease', 'start': 575, 'end': 584, 'mesh': 'D050723'}, {'text': 'magnesium', 'type': 'Chemical', 'start': 639, 'end': 648, 'mesh': 'D008274'}, {'text': 'potassium', 'type': 'Chemical', 'start': 654, 'end': 663, 'mesh': 'D011188'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 734, 'end': 741, 'mesh': 'D000431'}, {'text': 'creatine', 'type': 'Chemical', 'start': 856, 'end': 864, 'mesh': 'D003401'}, {'text': 'heparin', 'type': 'Chemical', 'start': 968, 'end': 975, 'mesh': 'D006493'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 999, 'end': 1008, 'mesh': 'D004110'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 1042, 'end': 1052, 'mesh': 'D000638'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 1141, 'end': 1151, 'mesh': 'D008790'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1156, 'end': 1163, 'mesh': 'D001241'}, {'text': 'creatine', 'type': 'Chemical', 'start': 1258, 'end': 1266, 'mesh': 'D003401'}, {'text': 'creatine', 'type': 'Chemical', 'start': 1360, 'end': 1368, 'mesh': 'D003401'}, {'text': 'creatine', 'type': 'Chemical', 'start': 1491, 'end': 1499, 'mesh': 'D003401'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 1522, 'end': 1532, 'mesh': 'D001145'}]"
+389,15863244,Comparison of developmental toxicity of selective and non-selective cyclooxygenase-2 inhibitors in CRL:(WI)WUBR Wistar rats--DFU and piroxicam study.,"BACKGROUND: Cyclooxygenase (COX) inhibitors are one of the most often ingested drugs during pregnancy. Unlike general toxicity data, their prenatal toxic effects were not extensively studied before. The aim of the experiment was to evaluate the developmental toxicity of the non-selective (piroxicam) and selective (DFU; 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanon) COX-2 inhibitors. METHODS: Drugs were separately, orally once daily dosed to pregnant rats from day 8 to 21 (GD1=plug day). Doses were set at 0.3, 3.0 and 30.0mg/kg for piroxicam and 0.2, 2.0 and 20.0mg/kg for DFU. Fetuses were delivered on GD 21 and routinely examined. Comprehensive clinical and developmental measurements were done. The pooled statistical analysis for ventricular septal (VSD) and midline (MD) defects was performed for rat fetuses exposed to piroxicam, selective and non-selective COX-2 inhibitor based on present and historic data. RESULTS: Maternal toxicity, intrauterine growth retardation, and increase of external and skeletal variations were found in rats treated with the highest dose of piroxicam. Decrease of fetal length was the only signs of the DFU developmental toxicity observed in pups exposed to the highest compound dose. Lack of teratogenicity was found in piroxicam and DFU-exposed groups. Prenatal exposure to non-selective COX inhibitors increases the risk of VSD and MD when compared to historic control but not with selective COX-2 inhibitors. CONCLUSION: Both selective and non-selective COX-2 inhibitors were toxic for rats fetuses when administered in the highest dose. Unlike DFU, piroxicam was also highly toxic to the dams. Prenatal exposure to selective COX-2 inhibitors does not increase the risk of ventricular septal and midline defects in rat when compared to non-selective drugs and historic control.","[{'text': 'toxicity', 'type': 'Disease', 'start': 28, 'end': 36, 'mesh': 'D064420'}, {'text': 'DFU', 'type': 'Chemical', 'start': 125, 'end': 128, 'mesh': 'C106876'}, {'text': 'piroxicam', 'type': 'Chemical', 'start': 133, 'end': 142, 'mesh': 'D010894'}, {'text': 'toxicity', 'type': 'Disease', 'start': 268, 'end': 276, 'mesh': 'D064420'}, {'text': 'toxicity', 'type': 'Disease', 'start': 409, 'end': 417, 'mesh': 'D064420'}, {'text': 'piroxicam', 'type': 'Chemical', 'start': 440, 'end': 449, 'mesh': 'D010894'}, {'text': 'DFU', 'type': 'Chemical', 'start': 466, 'end': 469, 'mesh': 'C106876'}, {'text': '5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanon', 'type': 'Chemical', 'start': 471, 'end': 545, 'mesh': 'C106876'}, {'text': 'piroxicam', 'type': 'Chemical', 'start': 716, 'end': 725, 'mesh': 'D010894'}, {'text': 'DFU', 'type': 'Chemical', 'start': 757, 'end': 760, 'mesh': 'C106876'}, {'text': 'piroxicam', 'type': 'Chemical', 'start': 1010, 'end': 1019, 'mesh': 'D010894'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1119, 'end': 1127, 'mesh': 'D064420'}, {'text': 'intrauterine growth retardation', 'type': 'Disease', 'start': 1129, 'end': 1160, 'mesh': 'D005317'}, {'text': 'increase of external and skeletal variations', 'type': 'Disease', 'start': 1166, 'end': 1210, 'mesh': 'D009139'}, {'text': 'piroxicam', 'type': 'Chemical', 'start': 1263, 'end': 1272, 'mesh': 'D010894'}, {'text': 'DFU', 'type': 'Chemical', 'start': 1325, 'end': 1328, 'mesh': 'C106876'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1343, 'end': 1351, 'mesh': 'D064420'}, {'text': 'piroxicam', 'type': 'Chemical', 'start': 1443, 'end': 1452, 'mesh': 'D010894'}, {'text': 'DFU', 'type': 'Chemical', 'start': 1457, 'end': 1460, 'mesh': 'C106876'}, {'text': 'DFU', 'type': 'Chemical', 'start': 1771, 'end': 1774, 'mesh': 'C106876'}, {'text': 'piroxicam', 'type': 'Chemical', 'start': 1776, 'end': 1785, 'mesh': 'D010894'}]"
+390,12921865,Protective efficacy of neuroactive steroids against cocaine kindled-seizures in mice.,"Neuroactive steroids demonstrate pharmacological actions that have relevance for a host of neurological and psychiatric disorders. They offer protection against seizures in a range of models and seem to inhibit certain stages of drug dependence in preclinical assessments. The present study was designed to evaluate two endogenous and one synthetic neuroactive steroid that positively modulate the gamma-aminobutyric acid (GABA(A)) receptor against the increase in sensitivity to the convulsant effects of cocaine engendered by repeated cocaine administration (seizure kindling). Allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one), pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) and ganaxolone (a synthetic derivative of allopregnanolone 3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) were tested for their ability to suppress the expression (anticonvulsant effect) and development (antiepileptogenic effect) of cocaine-kindled seizures in male, Swiss-Webster mice. Kindled seizures were induced by daily administration of 60 mg/kg cocaine for 5 days. All of these positive GABA(A) modulators suppressed the expression of kindled seizures, whereas only allopregnanolone and ganaxolone inhibited the development of kindling. Allopregnanolone and pregnanolone, but not ganaxolone, also reduced cumulative lethality associated with kindling. These findings demonstrate that some neuroactive steroids attenuate convulsant and sensitizing properties of cocaine and add to a growing literature on their potential use in the modulation of effects of drugs of abuse.","[{'text': 'steroids', 'type': 'Chemical', 'start': 35, 'end': 43, 'mesh': 'D013256'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 52, 'end': 59, 'mesh': 'D003042'}, {'text': 'seizures', 'type': 'Disease', 'start': 68, 'end': 76, 'mesh': 'D012640'}, {'text': 'steroids', 'type': 'Chemical', 'start': 98, 'end': 106, 'mesh': 'D013256'}, {'text': 'seizures', 'type': 'Disease', 'start': 247, 'end': 255, 'mesh': 'D012640'}, {'text': 'drug dependence', 'type': 'Disease', 'start': 315, 'end': 330, 'mesh': 'D019966'}, {'text': 'steroid', 'type': 'Chemical', 'start': 447, 'end': 454, 'mesh': 'D013256'}, {'text': 'gamma-aminobutyric acid', 'type': 'Chemical', 'start': 484, 'end': 507, 'mesh': 'D005680'}, {'text': 'GABA', 'type': 'Chemical', 'start': 509, 'end': 513, 'mesh': 'D005680'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 592, 'end': 599, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 623, 'end': 630, 'mesh': 'D003042'}, {'text': 'seizure', 'type': 'Disease', 'start': 647, 'end': 654, 'mesh': 'D012640'}, {'text': 'Allopregnanolone', 'type': 'Chemical', 'start': 666, 'end': 682, 'mesh': 'D011280'}, {'text': '3alpha-hydroxy-5alpha-pregnan-20-one', 'type': 'Chemical', 'start': 684, 'end': 720, 'mesh': 'D011280'}, {'text': 'pregnanolone', 'type': 'Chemical', 'start': 723, 'end': 735, 'mesh': 'D011280'}, {'text': '3alpha-hydroxy-5beta-pregnan-20-one', 'type': 'Chemical', 'start': 737, 'end': 772, 'mesh': 'D011280'}, {'text': 'ganaxolone', 'type': 'Chemical', 'start': 778, 'end': 788, 'mesh': 'C105051'}, {'text': 'allopregnanolone', 'type': 'Chemical', 'start': 816, 'end': 832, 'mesh': 'D011280'}, {'text': '3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one', 'type': 'Chemical', 'start': 833, 'end': 882, 'mesh': 'C105051'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1011, 'end': 1018, 'mesh': 'D003042'}, {'text': 'seizures', 'type': 'Disease', 'start': 1027, 'end': 1035, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 1073, 'end': 1081, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1131, 'end': 1138, 'mesh': 'D003042'}, {'text': 'GABA', 'type': 'Chemical', 'start': 1173, 'end': 1177, 'mesh': 'D005680'}, {'text': 'seizures', 'type': 'Disease', 'start': 1229, 'end': 1237, 'mesh': 'D012640'}, {'text': 'allopregnanolone', 'type': 'Chemical', 'start': 1252, 'end': 1268, 'mesh': 'D011280'}, {'text': 'ganaxolone', 'type': 'Chemical', 'start': 1273, 'end': 1283, 'mesh': 'C105051'}, {'text': 'Allopregnanolone', 'type': 'Chemical', 'start': 1323, 'end': 1339, 'mesh': 'D011280'}, {'text': 'pregnanolone', 'type': 'Chemical', 'start': 1344, 'end': 1356, 'mesh': 'D011280'}, {'text': 'ganaxolone', 'type': 'Chemical', 'start': 1366, 'end': 1376, 'mesh': 'C105051'}, {'text': 'steroids', 'type': 'Chemical', 'start': 1487, 'end': 1495, 'mesh': 'D013256'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1547, 'end': 1554, 'mesh': 'D003042'}]"
+391,12584269,"Kidney function and morphology after short-term combination therapy with cyclosporine A, tacrolimus and sirolimus in the rat.","BACKGROUND: Sirolimus (SRL) may supplement calcineurin inhibitors in clinical organ transplantation. These are nephrotoxic, but SRL seems to act differently displaying only minor nephrotoxic effects, although this question is still open. In a number of treatment protocols where SRL was combined with a calcineurin inhibitor indications of a synergistic nephrotoxic effect were described. The aim of this study was to examine further the renal function, including morphological analysis of the kidneys of male Sprague-Dawley rats treated with either cyclosporine A (CsA), tacrolimus (FK506) or SRL as monotherapies or in different combinations. METHODS: For a period of 2 weeks, CsA 15 mg/kg/day (given orally), FK506 3.0 mg/kg/day (given orally) or SRL 0.4 mg/kg/day (given intraperitoneally) was administered once a day as these doses have earlier been found to achieve a significant immunosuppressive effect in Sprague-Dawley rats. In the 'conscious catheterized rat' model, the glomerular filtration rate (GFR) was measured as the clearance of Cr(EDTA). The morphological analysis of the kidneys included a semi-quantitative scoring system analysing the degree of striped fibrosis, subcapsular fibrosis and the number of basophilic tubules, plus an additional stereological analysis of the total grade of fibrosis in the cortex stained with Sirius Red. RESULTS: CsA, FK506 and SRL all significantly decreased the GFR. A further deterioration was seen when CsA was combined with either FK506 or SRL, whereas the GFR remained unchanged in the group treated with FK506 plus SRL when compared with treatment with any of the single substances. The morphological changes presented a similar pattern. The semi-quantitative scoring was significantly worst in the group treated with CsA plus SRL (P<0.001 compared with controls) and the analysis of the total grade of fibrosis also showed the highest proportion in the same group and was significantly different from controls (P<0.02). The FK506 plus SRL combination showed only a marginally higher degree of fibrosis as compared with controls (P=0.05). CONCLUSION: This rat study demonstrated a synergistic nephrotoxic effect of CsA plus SRL, whereas FK506 plus SRL was better tolerated.","[{'text': 'cyclosporine A', 'type': 'Chemical', 'start': 73, 'end': 87, 'mesh': 'D016572'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 89, 'end': 99, 'mesh': 'D016559'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 104, 'end': 113, 'mesh': 'D020123'}, {'text': 'Sirolimus', 'type': 'Chemical', 'start': 138, 'end': 147, 'mesh': 'D020123'}, {'text': 'SRL', 'type': 'Chemical', 'start': 149, 'end': 152, 'mesh': 'D020123'}, {'text': 'nephrotoxic', 'type': 'Disease', 'start': 237, 'end': 248, 'mesh': 'D007674'}, {'text': 'SRL', 'type': 'Chemical', 'start': 254, 'end': 257, 'mesh': 'D020123'}, {'text': 'nephrotoxic', 'type': 'Disease', 'start': 305, 'end': 316, 'mesh': 'D007674'}, {'text': 'SRL', 'type': 'Chemical', 'start': 405, 'end': 408, 'mesh': 'D020123'}, {'text': 'nephrotoxic', 'type': 'Disease', 'start': 480, 'end': 491, 'mesh': 'D007674'}, {'text': 'cyclosporine A', 'type': 'Chemical', 'start': 676, 'end': 690, 'mesh': 'D016572'}, {'text': 'CsA', 'type': 'Chemical', 'start': 692, 'end': 695, 'mesh': 'D016572'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 698, 'end': 708, 'mesh': 'D016559'}, {'text': 'FK506', 'type': 'Chemical', 'start': 710, 'end': 715, 'mesh': 'D016559'}, {'text': 'SRL', 'type': 'Chemical', 'start': 720, 'end': 723, 'mesh': 'D020123'}, {'text': 'CsA', 'type': 'Chemical', 'start': 805, 'end': 808, 'mesh': 'D016572'}, {'text': 'FK506', 'type': 'Chemical', 'start': 838, 'end': 843, 'mesh': 'D016559'}, {'text': 'SRL', 'type': 'Chemical', 'start': 876, 'end': 879, 'mesh': 'D020123'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 1302, 'end': 1310, 'mesh': 'D005355'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 1324, 'end': 1332, 'mesh': 'D005355'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 1435, 'end': 1443, 'mesh': 'D005355'}, {'text': 'CsA', 'type': 'Chemical', 'start': 1492, 'end': 1495, 'mesh': 'D016572'}, {'text': 'FK506', 'type': 'Chemical', 'start': 1497, 'end': 1502, 'mesh': 'D016559'}, {'text': 'SRL', 'type': 'Chemical', 'start': 1507, 'end': 1510, 'mesh': 'D020123'}, {'text': 'CsA', 'type': 'Chemical', 'start': 1586, 'end': 1589, 'mesh': 'D016572'}, {'text': 'FK506', 'type': 'Chemical', 'start': 1615, 'end': 1620, 'mesh': 'D016559'}, {'text': 'SRL', 'type': 'Chemical', 'start': 1624, 'end': 1627, 'mesh': 'D020123'}, {'text': 'FK506', 'type': 'Chemical', 'start': 1690, 'end': 1695, 'mesh': 'D016559'}, {'text': 'SRL', 'type': 'Chemical', 'start': 1701, 'end': 1704, 'mesh': 'D020123'}, {'text': 'CsA', 'type': 'Chemical', 'start': 1904, 'end': 1907, 'mesh': 'D016572'}, {'text': 'SRL', 'type': 'Chemical', 'start': 1913, 'end': 1916, 'mesh': 'D020123'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 1989, 'end': 1997, 'mesh': 'D005355'}, {'text': 'FK506', 'type': 'Chemical', 'start': 2111, 'end': 2116, 'mesh': 'D016559'}, {'text': 'SRL', 'type': 'Chemical', 'start': 2122, 'end': 2125, 'mesh': 'D020123'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 2180, 'end': 2188, 'mesh': 'D005355'}, {'text': 'nephrotoxic', 'type': 'Disease', 'start': 2279, 'end': 2290, 'mesh': 'D007674'}, {'text': 'CsA', 'type': 'Chemical', 'start': 2301, 'end': 2304, 'mesh': 'D016572'}, {'text': 'SRL', 'type': 'Chemical', 'start': 2310, 'end': 2313, 'mesh': 'D020123'}, {'text': 'FK506', 'type': 'Chemical', 'start': 2323, 'end': 2328, 'mesh': 'D016559'}, {'text': 'SRL', 'type': 'Chemical', 'start': 2334, 'end': 2337, 'mesh': 'D020123'}]"
+392,10406016,Effect of fucoidan treatment on collagenase-induced intracerebral hemorrhage in rats.,"Inflammatory cells are postulated to mediate some of the brain damage following ischemic stroke. Intracerebral hemorrhage is associated with more inflammation than ischemic stroke. We tested the sulfated polysaccharide fucoidan, which has been reported to reduce inflammatory brain damage, in a rat model of intracerebral hemorrhage induced by injection of bacterial collagenase into the caudate nucleus. Rats were treated with seven day intravenous infusion of fucoidan (30 micrograms h-1) or vehicle. The hematoma was assessed in vivo by magnetic resonance imaging. Motor behavior, passive avoidance, and skilled forelimb function were tested repeatedly for six weeks. Fucoidan-treated rats exhibited evidence of impaired blood clotting and hemodilution, had larger hematomas, and tended to have less inflammation in the vicinity of the hematoma after three days. They showed significantly more rapid improvement of motor function in the first week following hemorrhage and better memory retention in the passive avoidance test. Acute white matter edema and eventual neuronal loss in the striatum adjacent to the hematoma did not differ between the two groups. Investigation of more specific anti-inflammatory agents and hemodiluting agents are warranted in intracerebral hemorrhage.","[{'text': 'fucoidan', 'type': 'Chemical', 'start': 10, 'end': 18, 'mesh': 'C007789'}, {'text': 'intracerebral hemorrhage', 'type': 'Disease', 'start': 52, 'end': 76, 'mesh': 'D002543'}, {'text': 'brain damage', 'type': 'Disease', 'start': 143, 'end': 155, 'mesh': 'D001925'}, {'text': 'ischemic stroke', 'type': 'Disease', 'start': 166, 'end': 181, 'mesh': 'D002544'}, {'text': 'Intracerebral hemorrhage', 'type': 'Disease', 'start': 183, 'end': 207, 'mesh': 'D002543'}, {'text': 'inflammation', 'type': 'Disease', 'start': 232, 'end': 244, 'mesh': 'D007249'}, {'text': 'ischemic stroke', 'type': 'Disease', 'start': 250, 'end': 265, 'mesh': 'D002544'}, {'text': 'fucoidan', 'type': 'Chemical', 'start': 305, 'end': 313, 'mesh': 'C007789'}, {'text': 'brain damage', 'type': 'Disease', 'start': 362, 'end': 374, 'mesh': 'D001925'}, {'text': 'intracerebral hemorrhage', 'type': 'Disease', 'start': 394, 'end': 418, 'mesh': 'D002543'}, {'text': 'fucoidan', 'type': 'Chemical', 'start': 548, 'end': 556, 'mesh': 'C007789'}, {'text': 'hematoma', 'type': 'Disease', 'start': 593, 'end': 601, 'mesh': 'D006406'}, {'text': 'Fucoidan', 'type': 'Chemical', 'start': 757, 'end': 765, 'mesh': 'C007789'}, {'text': 'impaired blood clotting', 'type': 'Disease', 'start': 801, 'end': 824, 'mesh': 'D020141'}, {'text': 'hemodilution', 'type': 'Disease', 'start': 829, 'end': 841, 'mesh': 'D020141'}, {'text': 'hematomas', 'type': 'Disease', 'start': 854, 'end': 863, 'mesh': 'D006406'}, {'text': 'inflammation', 'type': 'Disease', 'start': 889, 'end': 901, 'mesh': 'D007249'}, {'text': 'hematoma', 'type': 'Disease', 'start': 925, 'end': 933, 'mesh': 'D006406'}, {'text': 'hemorrhage', 'type': 'Disease', 'start': 1047, 'end': 1057, 'mesh': 'D006470'}, {'text': 'white matter edema', 'type': 'Disease', 'start': 1123, 'end': 1141, 'mesh': 'D001929'}, {'text': 'neuronal loss', 'type': 'Disease', 'start': 1155, 'end': 1168, 'mesh': 'D009410'}, {'text': 'hematoma', 'type': 'Disease', 'start': 1201, 'end': 1209, 'mesh': 'D006406'}, {'text': 'intracerebral hemorrhage', 'type': 'Disease', 'start': 1346, 'end': 1370, 'mesh': 'D002543'}]"
+393,3403780,"Paracetamol-associated coma, metabolic acidosis, renal and hepatic failure.","A case of metabolic acidosis, acute renal failure and hepatic failure following paracetamol ingestion is presented. The diagnostic difficulty at presentation is highlighted. Continuous arteriovenous haemofiltration proved a valuable means of maintaining fluid and electrolyte balance. The patient recovered.","[{'text': 'Paracetamol', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D000082'}, {'text': 'coma', 'type': 'Disease', 'start': 23, 'end': 27, 'mesh': 'D003128'}, {'text': 'metabolic acidosis', 'type': 'Disease', 'start': 29, 'end': 47, 'mesh': 'D000138'}, {'text': 'metabolic acidosis', 'type': 'Disease', 'start': 86, 'end': 104, 'mesh': 'D000138'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 156, 'end': 167, 'mesh': 'D000082'}]"
+394,3101906,Hepatic reactions associated with ketoconazole in the United Kingdom.,"Ketoconazole was introduced in the United Kingdom in 1981. By November 1984 the Committee on Safety of Medicines had received 82 reports of possible hepatotoxicity associated with the drug, including five deaths. An analysis of the 75 cases that had been adequately followed up suggested that 16, including three deaths, were probably related to treatment with the drug. Of the remainder, 48 were possibly related to treatment, five were unlikely to be so, and six were unclassifiable. The mean age of patients in the 16 probable cases was 57.9, with hepatotoxicity being more common in women. The average duration of treatment before the onset of jaundice was 61 days. None of these well validated cases occurred within the first 10 days after treatment. The results of serum liver function tests suggested hepatocellular injury in 10 (63%); the rest showed a mixed pattern. In contrast, the results of histological examination of the liver often showed evidence of cholestasis. The characteristics of the 48 patients in the possible cases were similar. Allergic manifestations such as rash and eosinophilia were rare. Hepatitis was usually reversible when treatment was stopped, with the results of liver function tests returning to normal after an average of 3.1 months. In two of the three deaths probably associated with ketoconazole treatment the drug had been continued after the onset of jaundice and other symptoms of hepatitis. Clinical and biochemical monitoring at regular intervals for evidence of hepatitis is advised during long term treatment with ketoconazole to prevent possible serious hepatic injury.","[{'text': 'ketoconazole', 'type': 'Chemical', 'start': 34, 'end': 46, 'mesh': 'D007654'}, {'text': 'Ketoconazole', 'type': 'Chemical', 'start': 70, 'end': 82, 'mesh': 'D007654'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 219, 'end': 233, 'mesh': 'D056486'}, {'text': 'deaths', 'type': 'Disease', 'start': 275, 'end': 281, 'mesh': 'D003643'}, {'text': 'deaths', 'type': 'Disease', 'start': 383, 'end': 389, 'mesh': 'D003643'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 621, 'end': 635, 'mesh': 'D056486'}, {'text': 'jaundice', 'type': 'Disease', 'start': 718, 'end': 726, 'mesh': 'D007565'}, {'text': 'hepatocellular injury', 'type': 'Disease', 'start': 878, 'end': 899, 'mesh': 'D056486'}, {'text': 'cholestasis', 'type': 'Disease', 'start': 1037, 'end': 1048, 'mesh': 'D002779'}, {'text': 'rash', 'type': 'Disease', 'start': 1157, 'end': 1161, 'mesh': 'D005076'}, {'text': 'eosinophilia', 'type': 'Disease', 'start': 1166, 'end': 1178, 'mesh': 'D004802'}, {'text': 'Hepatitis', 'type': 'Disease', 'start': 1190, 'end': 1199, 'mesh': 'D056486'}, {'text': 'deaths', 'type': 'Disease', 'start': 1364, 'end': 1370, 'mesh': 'D003643'}, {'text': 'ketoconazole', 'type': 'Chemical', 'start': 1396, 'end': 1408, 'mesh': 'D007654'}, {'text': 'jaundice', 'type': 'Disease', 'start': 1466, 'end': 1474, 'mesh': 'D007565'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 1497, 'end': 1506, 'mesh': 'D056486'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 1581, 'end': 1590, 'mesh': 'D056486'}, {'text': 'ketoconazole', 'type': 'Chemical', 'start': 1634, 'end': 1646, 'mesh': 'D007654'}, {'text': 'hepatic injury', 'type': 'Disease', 'start': 1675, 'end': 1689, 'mesh': 'D056486'}]"
+395,9088814,Combined effects of prolonged prostaglandin E1-induced hypotension and haemodilution on human hepatic function.,"Combined effects of prolonged prostaglandin E1 (PGE1)-induced hypotension and haemodilution on hepatic function were studied in 30 patients undergoing hip surgery. The patients were randomly allocated to one of three groups; those in group A (n = 10) were subjected to controlled hypotension alone, those in group B (n = 10) to haemodilution alone and those in group C (n = 10) to both controlled hypotension and haemodilution. Haemodilution in groups B and C was produced by withdrawing approximately 1000 mL of blood and replacing it with the same amount of dextran solution, and final haematocrit values were 21 or 22%. Controlled hypotension in groups A and C was induced with PGE1 to maintain mean arterial blood pressure at 55 mmHg for 180 min. Measurements included arterial ketone body ratio (AKBR, aceto-acetate/3-hydroxybutyrate) and clinical hepatic function parameters. AKBR and biological hepatic function tests showed no change throughout the time course in groups A and B. In group C, AKBR showed a significant decrease at 120 min (-40%) and at 180 min (-49%) after the start of hypotension and at 60 min (-32%) after recovery of normotension, and SGOT, SGPT, LDH and total bilirubin showed significant increases after operation. The results suggest that a prolonged combination of more than 120 min of PGE1-induced hypotension and moderate haemodilution would cause impairment of hepatic function.","[{'text': 'prostaglandin E1', 'type': 'Chemical', 'start': 30, 'end': 46, 'mesh': 'D000527'}, {'text': 'hypotension', 'type': 'Disease', 'start': 55, 'end': 66, 'mesh': 'D007022'}, {'text': 'haemodilution', 'type': 'Disease', 'start': 71, 'end': 84, 'mesh': 'D020141'}, {'text': 'prostaglandin E1', 'type': 'Chemical', 'start': 142, 'end': 158, 'mesh': 'D000527'}, {'text': 'PGE1', 'type': 'Chemical', 'start': 160, 'end': 164, 'mesh': 'D000527'}, {'text': 'hypotension', 'type': 'Disease', 'start': 174, 'end': 185, 'mesh': 'D007022'}, {'text': 'haemodilution', 'type': 'Disease', 'start': 190, 'end': 203, 'mesh': 'D020141'}, {'text': 'hypotension', 'type': 'Disease', 'start': 392, 'end': 403, 'mesh': 'D007022'}, {'text': 'haemodilution', 'type': 'Disease', 'start': 440, 'end': 453, 'mesh': 'D020141'}, {'text': 'hypotension', 'type': 'Disease', 'start': 509, 'end': 520, 'mesh': 'D007022'}, {'text': 'haemodilution', 'type': 'Disease', 'start': 525, 'end': 538, 'mesh': 'D020141'}, {'text': 'Haemodilution', 'type': 'Disease', 'start': 540, 'end': 553, 'mesh': 'D020141'}, {'text': 'dextran', 'type': 'Chemical', 'start': 672, 'end': 679, 'mesh': 'D003911'}, {'text': 'hypotension', 'type': 'Disease', 'start': 746, 'end': 757, 'mesh': 'D007022'}, {'text': 'PGE1', 'type': 'Chemical', 'start': 793, 'end': 797, 'mesh': 'D000527'}, {'text': 'aceto-acetate', 'type': 'Chemical', 'start': 919, 'end': 932, 'mesh': 'C016635'}, {'text': '3-hydroxybutyrate', 'type': 'Chemical', 'start': 933, 'end': 950, 'mesh': 'D020155'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1206, 'end': 1217, 'mesh': 'D007022'}, {'text': 'bilirubin', 'type': 'Chemical', 'start': 1301, 'end': 1310, 'mesh': 'D001663'}, {'text': 'PGE1', 'type': 'Chemical', 'start': 1430, 'end': 1434, 'mesh': 'D000527'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1443, 'end': 1454, 'mesh': 'D007022'}, {'text': 'haemodilution', 'type': 'Disease', 'start': 1468, 'end': 1481, 'mesh': 'D020141'}, {'text': 'impairment of hepatic function', 'type': 'Disease', 'start': 1494, 'end': 1524, 'mesh': 'D008107'}]"
+396,20880751,Levodopa-induced dyskinesias in patients with Parkinson's disease: filling the bench-to-bedside gap.,"Levodopa is the most effective drug for the treatment of Parkinson's disease. However, the long-term use of this dopamine precursor is complicated by highly disabling fluctuations and dyskinesias. Although preclinical and clinical findings suggest pulsatile stimulation of striatal postsynaptic receptors as a key mechanism underlying levodopa-induced dyskinesias, their pathogenesis is still unclear. In recent years, evidence from animal models of Parkinson's disease has provided important information to understand the effect of specific receptor and post-receptor molecular mechanisms underlying the development of dyskinetic movements. Recent preclinical and clinical data from promising lines of research focus on the differential role of presynaptic versus postsynaptic mechanisms, dopamine receptor subtypes, ionotropic and metabotropic glutamate receptors, and non-dopaminergic neurotransmitter systems in the pathophysiology of levodopa-induced dyskinesias.","[{'text': 'Levodopa', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 17, 'end': 28, 'mesh': 'D004409'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 46, 'end': 65, 'mesh': 'D010300'}, {'text': 'Levodopa', 'type': 'Chemical', 'start': 101, 'end': 109, 'mesh': 'D007980'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 158, 'end': 177, 'mesh': 'D010300'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 214, 'end': 222, 'mesh': 'D004298'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 285, 'end': 296, 'mesh': 'D004409'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 436, 'end': 444, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 453, 'end': 464, 'mesh': 'D004409'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 551, 'end': 570, 'mesh': 'D010300'}, {'text': 'dyskinetic movements', 'type': 'Disease', 'start': 721, 'end': 741, 'mesh': 'D004409'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 891, 'end': 899, 'mesh': 'D004298'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 947, 'end': 956, 'mesh': 'D018698'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1040, 'end': 1048, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 1057, 'end': 1068, 'mesh': 'D004409'}]"
+397,20080419,Prevention of seizures and reorganization of hippocampal functions by transplantation of bone marrow cells in the acute phase of experimental epilepsy.,"In this study, we investigated the therapeutic potential of bone marrow mononuclear cells (BMCs) in a model of epilepsy induced by pilocarpine in rats. BMCs obtained from green fluorescent protein (GFP) transgenic mice or rats were transplanted intravenously after induction of status epilepticus (SE). Spontaneous recurrent seizures (SRS) were monitored using Racine's seizure severity scale. All of the rats in the saline-treated epileptic control group developed SRS, whereas none of the BMC-treated epileptic animals had seizures in the short term (15 days after transplantation), regardless of the BMC source. Over the long-term chronic phase (120 days after transplantation), only 25% of BMC-treated epileptic animals had seizures, but with a lower frequency and duration compared to the epileptic control group. The density of hippocampal neurons in the brains of animals treated with BMCs was markedly preserved. At hippocampal Schaeffer collateral-CA1 synapses, long-term potentiation was preserved in BMC-transplanted rats compared to epileptic controls. The donor-derived GFP(+) cells were rarely found in the brains of transplanted epileptic rats. In conclusion, treatment with BMCs can prevent the development of chronic seizures, reduce neuronal loss, and influence the reorganization of the hippocampal neuronal network.","[{'text': 'seizures', 'type': 'Disease', 'start': 14, 'end': 22, 'mesh': 'D012640'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 142, 'end': 150, 'mesh': 'D004827'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 263, 'end': 271, 'mesh': 'D004827'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 283, 'end': 294, 'mesh': 'D010862'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 430, 'end': 448, 'mesh': 'D013226'}, {'text': 'SE', 'type': 'Disease', 'start': 450, 'end': 452, 'mesh': 'D013226'}, {'text': 'Spontaneous recurrent seizures', 'type': 'Disease', 'start': 455, 'end': 485, 'mesh': '-1'}, {'text': 'SRS', 'type': 'Disease', 'start': 487, 'end': 490, 'mesh': '-1'}, {'text': 'seizure', 'type': 'Disease', 'start': 522, 'end': 529, 'mesh': 'D012640'}, {'text': 'epileptic', 'type': 'Disease', 'start': 584, 'end': 593, 'mesh': 'D004827'}, {'text': 'SRS', 'type': 'Disease', 'start': 618, 'end': 621, 'mesh': '-1'}, {'text': 'epileptic', 'type': 'Disease', 'start': 655, 'end': 664, 'mesh': 'D004827'}, {'text': 'seizures', 'type': 'Disease', 'start': 677, 'end': 685, 'mesh': 'D012640'}, {'text': 'epileptic', 'type': 'Disease', 'start': 858, 'end': 867, 'mesh': 'D004827'}, {'text': 'seizures', 'type': 'Disease', 'start': 880, 'end': 888, 'mesh': 'D012640'}, {'text': 'epileptic', 'type': 'Disease', 'start': 946, 'end': 955, 'mesh': 'D004827'}, {'text': 'epileptic', 'type': 'Disease', 'start': 1197, 'end': 1206, 'mesh': 'D004827'}, {'text': 'epileptic', 'type': 'Disease', 'start': 1296, 'end': 1305, 'mesh': 'D004827'}, {'text': 'seizures', 'type': 'Disease', 'start': 1386, 'end': 1394, 'mesh': 'D012640'}, {'text': 'neuronal loss', 'type': 'Disease', 'start': 1403, 'end': 1416, 'mesh': 'D009410'}]"
+398,19445921,Cardioprotective effect of salvianolic acid A on isoproterenol-induced myocardial infarction in rats.,"The present study was designed to evaluate the cardioprotective potential of salvianolic acid A on isoproterenol-induced myocardial infarction in rats. Hemodynamic parameters and lead II electrocardiograph were monitored and recorded continuously. Cardiac marker enzymes and antioxidative parameters in serum and heart tissues were measured. Assay for mitochondrial respiratory function and histopathological examination of heart tissues were performed. Isoproterenol-treated rats showed significant increases in the levels of lactate dehydrogenase, aspartate transaminase, creatine kinase and malondialdehyde and significant decreases in the activities of superoxide dismutase, catalase and glutathione peroxidase in serum and heart. These rats also showed declines in left ventricular systolic pressure, maximum and minimum rate of developed left ventricular pressure, and elevation of left ventricular end-diastolic pressure and ST-segment. In addition, mitochondrial respiratory dysfunction characterized by decreased respiratory control ratio and ADP/O was observed in isoproterenol-treated rats. Administration of salvianolic acid A for a period of 8 days significantly attenuated isoproterenol-induced cardiac dysfunction and myocardial injury and improved mitochondrial respiratory function. The protective role of salvianolic acid A against isoproterenol-induced myocardial damage was further confirmed by histopathological examination. The results of our study suggest that salvianolic acid A possessing antioxidant activity has a significant protective effect against isoproterenol-induced myocardial infarction.","[{'text': 'salvianolic acid A', 'type': 'Chemical', 'start': 27, 'end': 45, 'mesh': 'C066201'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 49, 'end': 62, 'mesh': 'D007545'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 71, 'end': 92, 'mesh': 'D009203'}, {'text': 'salvianolic acid A', 'type': 'Chemical', 'start': 179, 'end': 197, 'mesh': 'C066201'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 201, 'end': 214, 'mesh': 'D007545'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 223, 'end': 244, 'mesh': 'D009203'}, {'text': 'Isoproterenol', 'type': 'Chemical', 'start': 556, 'end': 569, 'mesh': 'D007545'}, {'text': 'lactate', 'type': 'Chemical', 'start': 629, 'end': 636, 'mesh': 'D019344'}, {'text': 'aspartate', 'type': 'Chemical', 'start': 652, 'end': 661, 'mesh': 'D001224'}, {'text': 'creatine', 'type': 'Chemical', 'start': 676, 'end': 684, 'mesh': 'D003401'}, {'text': 'malondialdehyde', 'type': 'Chemical', 'start': 696, 'end': 711, 'mesh': 'D008315'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 759, 'end': 769, 'mesh': 'D013481'}, {'text': 'glutathione', 'type': 'Chemical', 'start': 794, 'end': 805, 'mesh': 'D005978'}, {'text': 'respiratory dysfunction', 'type': 'Disease', 'start': 1073, 'end': 1096, 'mesh': 'D012131'}, {'text': 'ADP', 'type': 'Chemical', 'start': 1154, 'end': 1157, 'mesh': 'D000244'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1176, 'end': 1189, 'mesh': 'D007545'}, {'text': 'salvianolic acid A', 'type': 'Chemical', 'start': 1222, 'end': 1240, 'mesh': 'C066201'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1289, 'end': 1302, 'mesh': 'D007545'}, {'text': 'cardiac dysfunction', 'type': 'Disease', 'start': 1311, 'end': 1330, 'mesh': 'D006331'}, {'text': 'myocardial injury', 'type': 'Disease', 'start': 1335, 'end': 1352, 'mesh': 'D009202'}, {'text': 'salvianolic acid A', 'type': 'Chemical', 'start': 1425, 'end': 1443, 'mesh': 'C066201'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1452, 'end': 1465, 'mesh': 'D007545'}, {'text': 'myocardial damage', 'type': 'Disease', 'start': 1474, 'end': 1491, 'mesh': 'D009202'}, {'text': 'salvianolic acid A', 'type': 'Chemical', 'start': 1586, 'end': 1604, 'mesh': 'C066201'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1681, 'end': 1694, 'mesh': 'D007545'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 1703, 'end': 1724, 'mesh': 'D009203'}]"
+399,18439803,Acute effects of N-(2-propylpentanoyl)urea on hippocampal amino acid neurotransmitters in pilocarpine-induced seizure in rats.,"The present study aimed to investigate the anticonvulsant activity as well as the effects on the level of hippocampal amino acid neurotransmitters (glutamate, aspartate, glycine and GABA) of N-(2-propylpentanoyl)urea (VPU) in comparison to its parent compound, valproic acid (VPA). VPU was more potent than VPA, exhibiting the median effective dose (ED(50)) of 49 mg/kg in protecting rats against pilocarpine-induced seizure whereas the corresponding value for VPA was 322 mg/kg. In vivo microdialysis demonstrated that an intraperitoneal administration of pilocarpine induced a pronounced increment of hippocampal glutamate and aspartate whereas no significant change was observed on the level of glycine and GABA. Pretreatment with either VPU (50 and 100 mg/kg) or VPA (300 and 600 mg/kg) completely abolished pilocarpine-evoked increases in extracellular glutamate and aspartate. In addition, a statistically significant reduction was also observed on the level of GABA and glycine but less than a drastic reduction of glutamate and aspartate level. Based on the finding that VPU and VPA could protect the animals against pilocarpine-induced seizure it is suggested that the reduction of inhibitory amino acid neurotransmitters was comparatively minor and offset by a pronounced reduction of glutamate and aspartate. Therefore, like VPA, the finding that VPU could drastically reduce pilocarpine-induced increases in glutamate and aspartate should account, at least partly, for its anticonvulsant activity observed in pilocarpine-induced seizure in experimental animals. Some other mechanism than those being reported herein should be further investigated.","[{'text': 'N-(2-propylpentanoyl)urea', 'type': 'Chemical', 'start': 17, 'end': 42, 'mesh': 'C108761'}, {'text': 'amino acid', 'type': 'Chemical', 'start': 58, 'end': 68, 'mesh': 'D000596'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 90, 'end': 101, 'mesh': 'D010862'}, {'text': 'seizure', 'type': 'Disease', 'start': 110, 'end': 117, 'mesh': 'D012640'}, {'text': 'amino acid', 'type': 'Chemical', 'start': 245, 'end': 255, 'mesh': 'D000596'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 275, 'end': 284, 'mesh': 'D018698'}, {'text': 'aspartate', 'type': 'Chemical', 'start': 286, 'end': 295, 'mesh': 'D001224'}, {'text': 'glycine', 'type': 'Chemical', 'start': 297, 'end': 304, 'mesh': 'D005998'}, {'text': 'GABA', 'type': 'Chemical', 'start': 309, 'end': 313, 'mesh': 'D005680'}, {'text': 'N-(2-propylpentanoyl)urea', 'type': 'Chemical', 'start': 318, 'end': 343, 'mesh': 'C108761'}, {'text': 'VPU', 'type': 'Chemical', 'start': 345, 'end': 348, 'mesh': 'C108761'}, {'text': 'valproic acid', 'type': 'Chemical', 'start': 388, 'end': 401, 'mesh': 'D014635'}, {'text': 'VPA', 'type': 'Chemical', 'start': 403, 'end': 406, 'mesh': 'D014635'}, {'text': 'VPU', 'type': 'Chemical', 'start': 409, 'end': 412, 'mesh': 'C108761'}, {'text': 'VPA', 'type': 'Chemical', 'start': 434, 'end': 437, 'mesh': 'D014635'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 524, 'end': 535, 'mesh': 'D010862'}, {'text': 'seizure', 'type': 'Disease', 'start': 544, 'end': 551, 'mesh': 'D012640'}, {'text': 'VPA', 'type': 'Chemical', 'start': 588, 'end': 591, 'mesh': 'D014635'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 684, 'end': 695, 'mesh': 'D010862'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 742, 'end': 751, 'mesh': 'D018698'}, {'text': 'aspartate', 'type': 'Chemical', 'start': 756, 'end': 765, 'mesh': 'D001224'}, {'text': 'glycine', 'type': 'Chemical', 'start': 825, 'end': 832, 'mesh': 'D005998'}, {'text': 'GABA', 'type': 'Chemical', 'start': 837, 'end': 841, 'mesh': 'D005680'}, {'text': 'VPU', 'type': 'Chemical', 'start': 868, 'end': 871, 'mesh': 'C108761'}, {'text': 'VPA', 'type': 'Chemical', 'start': 894, 'end': 897, 'mesh': 'D014635'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 939, 'end': 950, 'mesh': 'D010862'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 985, 'end': 994, 'mesh': 'D018698'}, {'text': 'aspartate', 'type': 'Chemical', 'start': 999, 'end': 1008, 'mesh': 'D001224'}, {'text': 'GABA', 'type': 'Chemical', 'start': 1095, 'end': 1099, 'mesh': 'D005680'}, {'text': 'glycine', 'type': 'Chemical', 'start': 1104, 'end': 1111, 'mesh': 'D005998'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 1149, 'end': 1158, 'mesh': 'D018698'}, {'text': 'aspartate', 'type': 'Chemical', 'start': 1163, 'end': 1172, 'mesh': 'D001224'}, {'text': 'VPU', 'type': 'Chemical', 'start': 1206, 'end': 1209, 'mesh': 'C108761'}, {'text': 'VPA', 'type': 'Chemical', 'start': 1214, 'end': 1217, 'mesh': 'D014635'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1252, 'end': 1263, 'mesh': 'D010862'}, {'text': 'seizure', 'type': 'Disease', 'start': 1272, 'end': 1279, 'mesh': 'D012640'}, {'text': 'amino acid', 'type': 'Chemical', 'start': 1329, 'end': 1339, 'mesh': 'D000596'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 1422, 'end': 1431, 'mesh': 'D018698'}, {'text': 'aspartate', 'type': 'Chemical', 'start': 1436, 'end': 1445, 'mesh': 'D001224'}, {'text': 'VPA', 'type': 'Chemical', 'start': 1463, 'end': 1466, 'mesh': 'D014635'}, {'text': 'VPU', 'type': 'Chemical', 'start': 1485, 'end': 1488, 'mesh': 'C108761'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1514, 'end': 1525, 'mesh': 'D010862'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 1547, 'end': 1556, 'mesh': 'D018698'}, {'text': 'aspartate', 'type': 'Chemical', 'start': 1561, 'end': 1570, 'mesh': 'D001224'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1648, 'end': 1659, 'mesh': 'D010862'}, {'text': 'seizure', 'type': 'Disease', 'start': 1668, 'end': 1675, 'mesh': 'D012640'}]"
+400,17919553,Acute hepatitis attack after exposure to telithromycin.,"INTRODUCTION: Antibiotic-associated hepatotoxicity is rare. With widespread use of antimicrobial agents, however, hepatic injury occurs frequently, and among adverse drug reactions, idiosyncratic reactions are the most serious. CASE SUMMARY: A 25-year-old male patient, with a height of 175 cm and weight of 72 kg presented to Marmara University Hospital Emergency Department, Istanbul, Turkey, with 5 days' history of jaundice, malaise, nausea, and vomiting. He had been prescribed telithromycin 400 mg/d PO to treat an upper respiratory tract infection 7 days prior. Admission laboratory tests were as follows: alanine aminotransferase, 67 U/L (reference range, 10-37 U/L); aspartate aminotransferase, 98 U/L (10-40 U/L); alkaline phosphatase, 513 U/L (0-270 U/L); gamma-glutamyltransferase, 32 U/L (7-49 U/L); amylase, 46 U/L (0-220 U/L); total bilirubin, 20.1 mg/dL (0.2-1.0 mg/dL); direct bilirubin, 14.8 mg/dL (0-0.3 mg/dL); and albumin, 4.7 mg/dL (3.5-5.4 mg/dL). No toxin, alcohol, or other drugs were reported. The patient had suffered a previous episode of ""acute hepatitis of unknown origin,"" that occurred after telithromycin usage. Both incidents occurred within a year. DISCUSSION: Telithromycin is the first of the ketolide antibacterials to receive US Food and Drug Administration approval for clinical use. It has been associated with infrequent and usually reversible severe hepatic dysfunction. Based on a score of 8 on the Naranjo adverse drug reaction probability scale, telithromycin was the probable cause of acute hepatitis in this patient, and pathological findings suggested drug-induced toxic hepatitis. Recurrence of hepatitis attack might have been avoided if the initial incident had been communicated to the attending physician who prescribed telithromycin the second time. CONCLUSION: Here we report a case of acute hepatitis probably associated with the administration of telithromycin.","[{'text': 'hepatitis', 'type': 'Disease', 'start': 6, 'end': 15, 'mesh': 'D056486'}, {'text': 'telithromycin', 'type': 'Chemical', 'start': 41, 'end': 54, 'mesh': 'C106791'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 92, 'end': 106, 'mesh': 'D056486'}, {'text': 'hepatic injury', 'type': 'Disease', 'start': 170, 'end': 184, 'mesh': 'D056486'}, {'text': 'adverse drug reactions', 'type': 'Disease', 'start': 214, 'end': 236, 'mesh': 'D064420'}, {'text': 'jaundice', 'type': 'Disease', 'start': 475, 'end': 483, 'mesh': 'D007565'}, {'text': 'nausea', 'type': 'Disease', 'start': 494, 'end': 500, 'mesh': 'D009325'}, {'text': 'vomiting', 'type': 'Disease', 'start': 506, 'end': 514, 'mesh': 'D014839'}, {'text': 'telithromycin', 'type': 'Chemical', 'start': 539, 'end': 552, 'mesh': 'C106791'}, {'text': 'upper respiratory tract infection', 'type': 'Disease', 'start': 577, 'end': 610, 'mesh': 'D012141'}, {'text': 'alanine', 'type': 'Chemical', 'start': 669, 'end': 676, 'mesh': 'D000409'}, {'text': 'aspartate', 'type': 'Chemical', 'start': 732, 'end': 741, 'mesh': 'D001224'}, {'text': 'bilirubin', 'type': 'Chemical', 'start': 904, 'end': 913, 'mesh': 'D001663'}, {'text': 'bilirubin', 'type': 'Chemical', 'start': 950, 'end': 959, 'mesh': 'D001663'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 1037, 'end': 1044, 'mesh': 'D000431'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 1130, 'end': 1139, 'mesh': 'D056486'}, {'text': 'telithromycin', 'type': 'Chemical', 'start': 1180, 'end': 1193, 'mesh': 'C106791'}, {'text': 'Telithromycin', 'type': 'Chemical', 'start': 1252, 'end': 1265, 'mesh': 'C106791'}, {'text': 'hepatic dysfunction', 'type': 'Disease', 'start': 1449, 'end': 1468, 'mesh': 'D008107'}, {'text': 'adverse drug reaction', 'type': 'Disease', 'start': 1507, 'end': 1528, 'mesh': 'D064420'}, {'text': 'telithromycin', 'type': 'Chemical', 'start': 1548, 'end': 1561, 'mesh': 'C106791'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 1594, 'end': 1603, 'mesh': 'D056486'}, {'text': 'toxic hepatitis', 'type': 'Disease', 'start': 1670, 'end': 1685, 'mesh': 'D056486'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 1701, 'end': 1710, 'mesh': 'D056486'}, {'text': 'telithromycin', 'type': 'Chemical', 'start': 1830, 'end': 1843, 'mesh': 'C106791'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 1904, 'end': 1913, 'mesh': 'D056486'}, {'text': 'telithromycin', 'type': 'Chemical', 'start': 1961, 'end': 1974, 'mesh': 'C106791'}]"
+401,15632880,Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure.,"BACKGROUND: A previous randomized controlled trial evaluating the use of spironolactone in heart failure patients reported a low risk of hyperkalemia (2%) and renal insufficiency (0%). Because treatments for heart failure have changed since the benefits of spironolactone were reported, the prevalence of these complications may differ in current clinical practice. We therefore sought to determine the prevalence and clinical associations of hyperkalemia and renal insufficiency in heart failure patients treated with spironolactone. METHODS: We performed a case control study of heart failure patients treated with spironolactone in our clinical practice. Cases were patients who developed hyperkalemia (K(+) >5.0 mEq/L) or renal insufficiency (Cr >or=2.5 mg/dL), and they were compared to 2 randomly selected controls per case. Clinical characteristics, medications, and serum chemistries at baseline and follow-up time periods were compared. RESULTS: Sixty-seven of 926 patients (7.2%) required discontinuation of spironolactone due to hyperkalemia (n = 33) or renal failure (n = 34). Patients who developed hyperkalemia were older and more likely to have diabetes, had higher baseline serum potassium levels and lower baseline potassium supplement doses, and were more likely to be treated with beta-blockers than controls (n = 134). Patients who developed renal insufficiency had lower baseline body weight and higher baseline serum creatinine, required higher doses of loop diuretics, and were more likely to be treated with thiazide diuretics than controls. CONCLUSIONS: Spironolactone-induced hyperkalemia and renal insufficiency are more common in our clinical experience than reported previously. This difference is explained by patient comorbidities and more frequent use of beta-blockers.","[{'text': 'Spironolactone', 'type': 'Chemical', 'start': 0, 'end': 14, 'mesh': 'D013148'}, {'text': 'renal insufficiency', 'type': 'Disease', 'start': 23, 'end': 42, 'mesh': 'D051437'}, {'text': 'hyperkalemia', 'type': 'Disease', 'start': 47, 'end': 59, 'mesh': 'D006947'}, {'text': 'heart failure', 'type': 'Disease', 'start': 77, 'end': 90, 'mesh': 'D006333'}, {'text': 'spironolactone', 'type': 'Chemical', 'start': 165, 'end': 179, 'mesh': 'D013148'}, {'text': 'heart failure', 'type': 'Disease', 'start': 183, 'end': 196, 'mesh': 'D006333'}, {'text': 'hyperkalemia', 'type': 'Disease', 'start': 229, 'end': 241, 'mesh': 'D006947'}, {'text': 'renal insufficiency', 'type': 'Disease', 'start': 251, 'end': 270, 'mesh': 'D051437'}, {'text': 'heart failure', 'type': 'Disease', 'start': 300, 'end': 313, 'mesh': 'D006333'}, {'text': 'spironolactone', 'type': 'Chemical', 'start': 349, 'end': 363, 'mesh': 'D013148'}, {'text': 'hyperkalemia', 'type': 'Disease', 'start': 535, 'end': 547, 'mesh': 'D006947'}, {'text': 'renal insufficiency', 'type': 'Disease', 'start': 552, 'end': 571, 'mesh': 'D051437'}, {'text': 'heart failure', 'type': 'Disease', 'start': 575, 'end': 588, 'mesh': 'D006333'}, {'text': 'spironolactone', 'type': 'Chemical', 'start': 611, 'end': 625, 'mesh': 'D013148'}, {'text': 'heart failure', 'type': 'Disease', 'start': 673, 'end': 686, 'mesh': 'D006333'}, {'text': 'spironolactone', 'type': 'Chemical', 'start': 709, 'end': 723, 'mesh': 'D013148'}, {'text': 'hyperkalemia', 'type': 'Disease', 'start': 784, 'end': 796, 'mesh': 'D006947'}, {'text': 'K', 'type': 'Chemical', 'start': 798, 'end': 799, 'mesh': 'D011188'}, {'text': 'renal insufficiency', 'type': 'Disease', 'start': 818, 'end': 837, 'mesh': 'D051437'}, {'text': 'Cr', 'type': 'Chemical', 'start': 839, 'end': 841, 'mesh': 'D002857'}, {'text': 'spironolactone', 'type': 'Chemical', 'start': 1110, 'end': 1124, 'mesh': 'D013148'}, {'text': 'hyperkalemia', 'type': 'Disease', 'start': 1132, 'end': 1144, 'mesh': 'D006947'}, {'text': 'renal failure', 'type': 'Disease', 'start': 1157, 'end': 1170, 'mesh': 'D051437'}, {'text': 'hyperkalemia', 'type': 'Disease', 'start': 1204, 'end': 1216, 'mesh': 'D006947'}, {'text': 'diabetes', 'type': 'Disease', 'start': 1252, 'end': 1260, 'mesh': 'D003920'}, {'text': 'potassium', 'type': 'Chemical', 'start': 1288, 'end': 1297, 'mesh': 'D011188'}, {'text': 'potassium', 'type': 'Chemical', 'start': 1324, 'end': 1333, 'mesh': 'D011188'}, {'text': 'renal insufficiency', 'type': 'Disease', 'start': 1454, 'end': 1473, 'mesh': 'D051437'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1531, 'end': 1541, 'mesh': 'D003404'}, {'text': 'thiazide', 'type': 'Chemical', 'start': 1624, 'end': 1632, 'mesh': 'D049971'}, {'text': 'Spironolactone', 'type': 'Chemical', 'start': 1671, 'end': 1685, 'mesh': 'D013148'}, {'text': 'hyperkalemia', 'type': 'Disease', 'start': 1694, 'end': 1706, 'mesh': 'D006947'}, {'text': 'renal insufficiency', 'type': 'Disease', 'start': 1711, 'end': 1730, 'mesh': 'D051437'}]"
+402,11773892,End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: risk of development and treatment.,"BACKGROUND: The calcineurin inhibitors cyclosporine and tacrolimus are both known to be nephrotoxic. Their use in orthotopic liver transplantation (OLTX) has dramatically improved success rates. Recently, however, we have had an increase of patients who are presenting after OLTX with end-stage renal disease (ESRD). This retrospective study examines the incidence and treatment of ESRD and chronic renal failure (CRF) in OLTX patients. METHODS: Patients receiving an OLTX only from June 1985 through December of 1994 who survived 6 months postoperatively were studied (n=834). Our prospectively collected database was the source of information. Patients were divided into three groups: Controls, no CRF or ESRD, n=748; CRF, sustained serum creatinine >2.5 mg/dl, n=41; and ESRD, n=45. Groups were compared for preoperative laboratory variables, diagnosis, postoperative variables, survival, type of ESRD therapy, and survival from onset of ESRD. RESULTS: At 13 years after OLTX, the incidence of severe renal dysfunction was 18.1% (CRF 8.6% and ESRD 9.5%). Compared with control patients, CRF and ESRD patients had higher preoperative serum creatinine levels, a greater percentage of patients with hepatorenal syndrome, higher percentage requirement for dialysis in the first 3 months postoperatively, and a higher 1-year serum creatinine. Multivariate stepwise logistic regression analysis using preoperative and postoperative variables identified that an increase of serum creatinine compared with average at 1 year, 3 months, and 4 weeks postoperatively were independent risk factors for the development of CRF or ESRD with odds ratios of 2.6, 2.2, and 1.6, respectively. Overall survival from the time of OLTX was not significantly different among groups, but by year 13, the survival of the patients who had ESRD was only 28.2% compared with 54.6% in the control group. Patients developing ESRD had a 6-year survival after onset of ESRD of 27% for the patients receiving hemodialysis versus 71.4% for the patients developing ESRD who subsequently received kidney transplants. CONCLUSIONS: Patients who are more than 10 years post-OLTX have CRF and ESRD at a high rate. The development of ESRD decreases survival, particularly in those patients treated with dialysis only. Patients who develop ESRD have a higher preoperative and 1-year serum creatinine and are more likely to have hepatorenal syndrome. However, an increase of serum creatinine at various times postoperatively is more predictive of the development of CRF or ESRD. New strategies for long-term immunosuppression may be needed to decrease this complication.","[{'text': 'End-stage renal disease', 'type': 'Disease', 'start': 0, 'end': 23, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 25, 'end': 29, 'mesh': 'D007676'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 190, 'end': 202, 'mesh': 'D016572'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 207, 'end': 217, 'mesh': 'D016559'}, {'text': 'nephrotoxic', 'type': 'Disease', 'start': 239, 'end': 250, 'mesh': 'D007674'}, {'text': 'end-stage renal disease', 'type': 'Disease', 'start': 436, 'end': 459, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 461, 'end': 465, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 533, 'end': 537, 'mesh': 'D007676'}, {'text': 'chronic renal failure', 'type': 'Disease', 'start': 542, 'end': 563, 'mesh': 'D007676'}, {'text': 'CRF', 'type': 'Disease', 'start': 565, 'end': 568, 'mesh': 'D007676'}, {'text': 'CRF', 'type': 'Disease', 'start': 851, 'end': 854, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 858, 'end': 862, 'mesh': 'D007676'}, {'text': 'CRF', 'type': 'Disease', 'start': 871, 'end': 874, 'mesh': 'D007676'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 892, 'end': 902, 'mesh': 'D003404'}, {'text': 'ESRD', 'type': 'Disease', 'start': 925, 'end': 929, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 1051, 'end': 1055, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 1092, 'end': 1096, 'mesh': 'D007676'}, {'text': 'renal dysfunction', 'type': 'Disease', 'start': 1155, 'end': 1172, 'mesh': 'D007674'}, {'text': 'CRF', 'type': 'Disease', 'start': 1184, 'end': 1187, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 1197, 'end': 1201, 'mesh': 'D007676'}, {'text': 'CRF', 'type': 'Disease', 'start': 1241, 'end': 1244, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 1249, 'end': 1253, 'mesh': 'D007676'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1293, 'end': 1303, 'mesh': 'D003404'}, {'text': 'hepatorenal syndrome', 'type': 'Disease', 'start': 1350, 'end': 1370, 'mesh': 'D006530'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1480, 'end': 1490, 'mesh': 'D003404'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1627, 'end': 1637, 'mesh': 'D003404'}, {'text': 'CRF', 'type': 'Disease', 'start': 1762, 'end': 1765, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 1769, 'end': 1773, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 1965, 'end': 1969, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 2047, 'end': 2051, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 2089, 'end': 2093, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 2182, 'end': 2186, 'mesh': 'D007676'}, {'text': 'CRF', 'type': 'Disease', 'start': 2297, 'end': 2300, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 2305, 'end': 2309, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 2345, 'end': 2349, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 2450, 'end': 2454, 'mesh': 'D007676'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 2499, 'end': 2509, 'mesh': 'D003404'}, {'text': 'hepatorenal syndrome', 'type': 'Disease', 'start': 2538, 'end': 2558, 'mesh': 'D006530'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 2590, 'end': 2600, 'mesh': 'D003404'}, {'text': 'CRF', 'type': 'Disease', 'start': 2675, 'end': 2678, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 2682, 'end': 2686, 'mesh': 'D007676'}]"
+403,10835440,Effect of intravenous nimodipine on blood pressure and outcome after acute stroke.,"BACKGROUND AND PURPOSE: The Intravenous Nimodipine West European Stroke Trial (INWEST) found a correlation between nimodipine-induced reduction in blood pressure (BP) and an unfavorable outcome in acute stroke. We sought to confirm this correlation with and without adjustment for prognostic variables and to investigate outcome in subgroups with increasing levels of BP reduction. METHODS: Patients with a clinical diagnosis of ischemic stroke (within 24 hours) were consecutively allocated to receive placebo (n=100), 1 mg/h (low-dose) nimodipine (n=101), or 2 mg/h (high-dose) nimodipine (n=94). The correlation between average BP change during the first 2 days and the outcome at day 21 was analyzed. RESULTS: Two hundred sixty-five patients were included in this analysis (n=92, 93, and 80 for placebo, low dose, and high dose, respectively). Nimodipine treatment resulted in a statistically significant reduction in systolic BP (SBP) and diastolic BP (DBP) from baseline compared with placebo during the first few days. In multivariate analysis, a significant correlation between DBP reduction and worsening of the neurological score was found for the high-dose group (beta=0.49, P=0. 048). Patients with a DBP reduction of > or =20% in the high-dose group had a significantly increased adjusted OR for the compound outcome variable death or dependency (Barthel Index <60) (n/N=25/26, OR 10. 16, 95% CI 1.02 to 101.74) and death alone (n/N=9/26, OR 4.336, 95% CI 1.131 16.619) compared with all placebo patients (n/N=62/92 and 14/92, respectively). There was no correlation between SBP change and outcome. CONCLUSIONS: DBP, but not SBP, reduction was associated with neurological worsening after the intravenous administration of high-dose nimodipine after acute stroke. For low-dose nimodipine, the results were not conclusive. These results do not confirm or exclude a neuroprotective property of nimodipine.","[{'text': 'nimodipine', 'type': 'Chemical', 'start': 22, 'end': 32, 'mesh': 'D009553'}, {'text': 'acute stroke', 'type': 'Disease', 'start': 69, 'end': 81, 'mesh': 'D020521'}, {'text': 'Nimodipine', 'type': 'Chemical', 'start': 123, 'end': 133, 'mesh': 'D009553'}, {'text': 'Stroke', 'type': 'Disease', 'start': 148, 'end': 154, 'mesh': 'D020521'}, {'text': 'nimodipine', 'type': 'Chemical', 'start': 198, 'end': 208, 'mesh': 'D009553'}, {'text': 'reduction in blood pressure', 'type': 'Disease', 'start': 217, 'end': 244, 'mesh': 'D007022'}, {'text': 'acute stroke', 'type': 'Disease', 'start': 280, 'end': 292, 'mesh': 'D020521'}, {'text': 'BP reduction', 'type': 'Disease', 'start': 451, 'end': 463, 'mesh': 'D007022'}, {'text': 'ischemic stroke', 'type': 'Disease', 'start': 512, 'end': 527, 'mesh': 'D002544'}, {'text': 'nimodipine', 'type': 'Chemical', 'start': 621, 'end': 631, 'mesh': 'D009553'}, {'text': 'nimodipine', 'type': 'Chemical', 'start': 663, 'end': 673, 'mesh': 'D009553'}, {'text': 'Nimodipine', 'type': 'Chemical', 'start': 931, 'end': 941, 'mesh': 'D009553'}, {'text': 'reduction in systolic BP', 'type': 'Disease', 'start': 992, 'end': 1016, 'mesh': 'D007022'}, {'text': 'DBP reduction', 'type': 'Disease', 'start': 1169, 'end': 1182, 'mesh': 'D007022'}, {'text': 'DBP reduction', 'type': 'Disease', 'start': 1296, 'end': 1309, 'mesh': 'D007022'}, {'text': 'death', 'type': 'Disease', 'start': 1422, 'end': 1427, 'mesh': 'D003643'}, {'text': 'death', 'type': 'Disease', 'start': 1512, 'end': 1517, 'mesh': 'D003643'}, {'text': 'nimodipine', 'type': 'Chemical', 'start': 1829, 'end': 1839, 'mesh': 'D009553'}, {'text': 'acute stroke', 'type': 'Disease', 'start': 1846, 'end': 1858, 'mesh': 'D020521'}, {'text': 'nimodipine', 'type': 'Chemical', 'start': 1873, 'end': 1883, 'mesh': 'D009553'}, {'text': 'nimodipine', 'type': 'Chemical', 'start': 1988, 'end': 1998, 'mesh': 'D009553'}]"
+404,9523805,Transient neurologic symptoms after spinal anesthesia: a lower incidence with prilocaine and bupivacaine than with lidocaine.,"BACKGROUND: Recent evidence suggests that transient neurologic symptoms (TNSs) frequently follow lidocaine spinal anesthesia but are infrequent with bupivacaine. However, identification of a short-acting local anesthetic to substitute for lidocaine for brief surgical procedures remains an important goal. Prilocaine is an amide local anesthetic with a duration of action similar to that of lidocaine. Accordingly, the present, prospective double-blind study compares prilocaine with lidocaine and bupivacaine with respect to duration of action and relative risk of TNSs. METHODS: Ninety patients classified as American Society of Anesthesiologists physical status I or II who were scheduled for short gynecologic procedures under spinal anesthesia were randomly allocated to receive 2.5 ml 2% lidocaine in 7.5% glucose, 2% prilocaine in 7.5% glucose, or 0.5% bupivacaine in 7.5% glucose. All solutions were provided in blinded vials by the hospital pharmacy. Details of spinal puncture, extension and regression of spinal block, and the times to reach discharge criteria were noted. In the evening of postoperative day 1, patients were evaluated for TNSs by a physician unaware of the drug administered and the details of the anesthetic procedure. RESULTS: Nine of 30 patients receiving lidocaine experienced TNSs, 1 of 30 patients receiving prilocaine (P = 0.03) had them, and none of 30 patients receiving bupivacaine had TNSs. Times to ambulate and to void were similar after lidocaine and prilocaine (150 vs. 165 min and 238 vs. 253 min, respectively) but prolonged after bupivacaine (200 and 299 min, respectively; P < 0.05). CONCLUSIONS: Prilocaine may be preferable to lidocaine for short surgical procedures because it has a similar duration of action but a lower incidence of TNSs.","[{'text': 'Transient neurologic symptoms', 'type': 'Disease', 'start': 0, 'end': 29, 'mesh': 'D009422'}, {'text': 'prilocaine', 'type': 'Chemical', 'start': 78, 'end': 88, 'mesh': 'D011318'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 93, 'end': 104, 'mesh': 'D002045'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 115, 'end': 124, 'mesh': 'D008012'}, {'text': 'transient neurologic symptoms', 'type': 'Disease', 'start': 168, 'end': 197, 'mesh': 'D009422'}, {'text': 'TNSs', 'type': 'Disease', 'start': 199, 'end': 203, 'mesh': 'D009422'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 223, 'end': 232, 'mesh': 'D008012'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 275, 'end': 286, 'mesh': 'D002045'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 365, 'end': 374, 'mesh': 'D008012'}, {'text': 'Prilocaine', 'type': 'Chemical', 'start': 432, 'end': 442, 'mesh': 'D011318'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 517, 'end': 526, 'mesh': 'D008012'}, {'text': 'prilocaine', 'type': 'Chemical', 'start': 594, 'end': 604, 'mesh': 'D011318'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 610, 'end': 619, 'mesh': 'D008012'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 624, 'end': 635, 'mesh': 'D002045'}, {'text': 'TNSs', 'type': 'Disease', 'start': 692, 'end': 696, 'mesh': 'D009422'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 920, 'end': 929, 'mesh': 'D008012'}, {'text': 'glucose', 'type': 'Chemical', 'start': 938, 'end': 945, 'mesh': 'D005947'}, {'text': 'prilocaine', 'type': 'Chemical', 'start': 950, 'end': 960, 'mesh': 'D011318'}, {'text': 'glucose', 'type': 'Chemical', 'start': 969, 'end': 976, 'mesh': 'D005947'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 986, 'end': 997, 'mesh': 'D002045'}, {'text': 'glucose', 'type': 'Chemical', 'start': 1006, 'end': 1013, 'mesh': 'D005947'}, {'text': 'TNSs', 'type': 'Disease', 'start': 1277, 'end': 1281, 'mesh': 'D009422'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 1414, 'end': 1423, 'mesh': 'D008012'}, {'text': 'TNSs', 'type': 'Disease', 'start': 1436, 'end': 1440, 'mesh': 'D009422'}, {'text': 'prilocaine', 'type': 'Chemical', 'start': 1469, 'end': 1479, 'mesh': 'D011318'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 1535, 'end': 1546, 'mesh': 'D002045'}, {'text': 'TNSs', 'type': 'Disease', 'start': 1551, 'end': 1555, 'mesh': 'D009422'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 1606, 'end': 1615, 'mesh': 'D008012'}, {'text': 'prilocaine', 'type': 'Chemical', 'start': 1620, 'end': 1630, 'mesh': 'D011318'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 1703, 'end': 1714, 'mesh': 'D002045'}, {'text': 'Prilocaine', 'type': 'Chemical', 'start': 1771, 'end': 1781, 'mesh': 'D011318'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 1803, 'end': 1812, 'mesh': 'D008012'}, {'text': 'TNSs', 'type': 'Disease', 'start': 1912, 'end': 1916, 'mesh': 'D009422'}]"
+405,9245658,The role of nicotine in smoking-related cardiovascular disease.,"Nicotine activates the sympathetic nervous system and in this way could contribute to cardiovascular disease. Animal studies and mechanistic studies indicate that nicotine could play a role in accelerating atherosclerosis, but evidence among humans is too inadequate to be definitive about such an effect. Almost certainly, nicotine via its hemodynamic effects contributes to acute cardiovascular events, although current evidence suggests that the effects of nicotine are much less important than are the prothrombotic effects of cigarette smoking or the effects of carbon monoxide. Nicotine does not appear to enhance thrombosis among humans. Clinical studies of pipe smokers and people using transdermal nicotine support the idea that toxins other than nicotine are the most important causes of acute cardiovascular events. Finally, the dose response for cardiovascular events of nicotine appears to be flat, suggesting that if nicotine is involved, adverse effects might be seen with relatively low-level cigarette exposures.","[{'text': 'nicotine', 'type': 'Chemical', 'start': 12, 'end': 20, 'mesh': 'D009538'}, {'text': 'cardiovascular disease', 'type': 'Disease', 'start': 40, 'end': 62, 'mesh': 'D002318'}, {'text': 'Nicotine', 'type': 'Chemical', 'start': 64, 'end': 72, 'mesh': 'D009538'}, {'text': 'cardiovascular disease', 'type': 'Disease', 'start': 150, 'end': 172, 'mesh': 'D002318'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 227, 'end': 235, 'mesh': 'D009538'}, {'text': 'atherosclerosis', 'type': 'Disease', 'start': 270, 'end': 285, 'mesh': 'D050197'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 388, 'end': 396, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 524, 'end': 532, 'mesh': 'D009538'}, {'text': 'carbon monoxide', 'type': 'Chemical', 'start': 631, 'end': 646, 'mesh': 'D002248'}, {'text': 'Nicotine', 'type': 'Chemical', 'start': 648, 'end': 656, 'mesh': 'D009538'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 684, 'end': 694, 'mesh': 'D013927'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 771, 'end': 779, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 820, 'end': 828, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 947, 'end': 955, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 995, 'end': 1003, 'mesh': 'D009538'}]"
+406,9034419,Seizure resulting from a venlafaxine overdose.,"OBJECTIVE: To report a case of venlafaxine overdose. CASE SUMMARY: A 40-year-old woman with major depression took an overdose of venlafaxine in an apparent suicide attempt. After the ingestion of 26 venlafaxine 50-mg tablets, the patient experienced a witnessed generalized seizure. She was admitted to the medical intensive care unit, venlafaxine was discontinued, and no further sequelae were seen. DISCUSSION: To our knowledge, this is the first reported case of venlafaxine overdose that resulted in a generalized seizure. Based on nonoverdose pharmacokinetics and pharmacodynamics of venlafaxine and the potential risks of available interventions, no emergent therapy was instituted. CONCLUSIONS: The venlafaxine overdose in our patient resulted in a single episode of generalized seizure but elicited no further sequelae.","[{'text': 'Seizure', 'type': 'Disease', 'start': 0, 'end': 7, 'mesh': 'D012640'}, {'text': 'venlafaxine', 'type': 'Chemical', 'start': 25, 'end': 36, 'mesh': 'C047426'}, {'text': 'overdose', 'type': 'Disease', 'start': 37, 'end': 45, 'mesh': 'D062787'}, {'text': 'venlafaxine', 'type': 'Chemical', 'start': 78, 'end': 89, 'mesh': 'C047426'}, {'text': 'overdose', 'type': 'Disease', 'start': 90, 'end': 98, 'mesh': 'D062787'}, {'text': 'major depression', 'type': 'Disease', 'start': 139, 'end': 155, 'mesh': 'D003865'}, {'text': 'overdose', 'type': 'Disease', 'start': 164, 'end': 172, 'mesh': 'D062787'}, {'text': 'venlafaxine', 'type': 'Chemical', 'start': 176, 'end': 187, 'mesh': 'C047426'}, {'text': 'venlafaxine', 'type': 'Chemical', 'start': 246, 'end': 257, 'mesh': 'C047426'}, {'text': 'seizure', 'type': 'Disease', 'start': 321, 'end': 328, 'mesh': 'D012640'}, {'text': 'venlafaxine', 'type': 'Chemical', 'start': 383, 'end': 394, 'mesh': 'C047426'}, {'text': 'venlafaxine', 'type': 'Chemical', 'start': 513, 'end': 524, 'mesh': 'C047426'}, {'text': 'overdose', 'type': 'Disease', 'start': 525, 'end': 533, 'mesh': 'D062787'}, {'text': 'seizure', 'type': 'Disease', 'start': 565, 'end': 572, 'mesh': 'D012640'}, {'text': 'venlafaxine', 'type': 'Chemical', 'start': 636, 'end': 647, 'mesh': 'C047426'}, {'text': 'venlafaxine', 'type': 'Chemical', 'start': 753, 'end': 764, 'mesh': 'C047426'}, {'text': 'overdose', 'type': 'Disease', 'start': 765, 'end': 773, 'mesh': 'D062787'}, {'text': 'seizure', 'type': 'Disease', 'start': 833, 'end': 840, 'mesh': 'D012640'}]"
+407,8829025,Effect of nifedipine on renal function in liver transplant recipients receiving tacrolimus.,"The effect of nifedipine on renal function in liver transplant recipients who were receiving tacrolimus was evaluated between January 1992 and January 1996. Two groups of patients receiving tacrolimus were compared over a period of 1 year, one group comprising hypertensive patients who were receiving nifedipine, and the other comprising nonhypertensive patients not receiving nifedipine. The time from transplant to baseline was similar in all patients. Nifedipine significantly improved kidney function as indicated by a significant lowering of serum creatinine levels at 6 and 12 months. The observed positive impact of nifedipine on reducing the nephrotoxicity associated with tacrolimus in liver transplant recipients should be an important factor in selecting an agent to treat hypertension in this population.","[{'text': 'nifedipine', 'type': 'Chemical', 'start': 10, 'end': 20, 'mesh': 'D009543'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 80, 'end': 90, 'mesh': 'D016559'}, {'text': 'nifedipine', 'type': 'Chemical', 'start': 106, 'end': 116, 'mesh': 'D009543'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 185, 'end': 195, 'mesh': 'D016559'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 282, 'end': 292, 'mesh': 'D016559'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 353, 'end': 365, 'mesh': 'D006973'}, {'text': 'nifedipine', 'type': 'Chemical', 'start': 394, 'end': 404, 'mesh': 'D009543'}, {'text': 'nifedipine', 'type': 'Chemical', 'start': 470, 'end': 480, 'mesh': 'D009543'}, {'text': 'Nifedipine', 'type': 'Chemical', 'start': 548, 'end': 558, 'mesh': 'D009543'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 646, 'end': 656, 'mesh': 'D003404'}, {'text': 'nifedipine', 'type': 'Chemical', 'start': 716, 'end': 726, 'mesh': 'D009543'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 743, 'end': 757, 'mesh': 'D007674'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 774, 'end': 784, 'mesh': 'D016559'}, {'text': 'hypertension', 'type': 'Disease', 'start': 877, 'end': 889, 'mesh': 'D006973'}]"
+408,8437969,Sinus arrest associated with continuous-infusion cimetidine.,"The administration of intermittent intravenous infusions of cimetidine is infrequently associated with the development of bradyarrhythmias. A 40-year-old man with leukemia and no history of cardiac disease developed recurrent, brief episodes of apparent sinus arrest while receiving continuous-infusion cimetidine 50 mg/hour. The arrhythmias were temporally related to cimetidine administration, disappeared after dechallenge, and did not recur during ranitidine treatment. This is the first reported case of sinus arrest associated with continuous-infusion cimetidine.","[{'text': 'Sinus arrest', 'type': 'Disease', 'start': 0, 'end': 12, 'mesh': 'D054138'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 49, 'end': 59, 'mesh': 'D002927'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 121, 'end': 131, 'mesh': 'D002927'}, {'text': 'bradyarrhythmias', 'type': 'Disease', 'start': 183, 'end': 199, 'mesh': 'D001919'}, {'text': 'leukemia', 'type': 'Disease', 'start': 224, 'end': 232, 'mesh': 'D007938'}, {'text': 'cardiac disease', 'type': 'Disease', 'start': 251, 'end': 266, 'mesh': 'D006331'}, {'text': 'sinus arrest', 'type': 'Disease', 'start': 315, 'end': 327, 'mesh': 'D054138'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 364, 'end': 374, 'mesh': 'D002927'}, {'text': 'arrhythmias', 'type': 'Disease', 'start': 391, 'end': 402, 'mesh': 'D001145'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 430, 'end': 440, 'mesh': 'D002927'}, {'text': 'ranitidine', 'type': 'Chemical', 'start': 513, 'end': 523, 'mesh': 'D011899'}, {'text': 'sinus arrest', 'type': 'Disease', 'start': 570, 'end': 582, 'mesh': 'D054138'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 619, 'end': 629, 'mesh': 'D002927'}]"
+409,7890216,Composition of gall bladder stones associated with octreotide: response to oral ursodeoxycholic acid.,"Octreotide, an effective treatment for acromegaly, induces gall bladder stones in 13-60% of patients. Because knowledge of stone composition is essential for studies of their pathogenesis, treatment, and prevention, this was investigated by direct and indirect methods in 14 octreotide treated acromegalic patients with gall stones. Chemical analysis of gall stones retrieved at cholecystectomy from two patients, showed that they contained 71% and 87% cholesterol by weight. In the remaining 12 patients, localised computed tomography of the gall bladder showed that eight had stones with maximum attenuation scores of < 100 Hounsfield units (values of < 100 HU predict cholesterol rich, dissolvable stones). Gall bladder bile was obtained by ultrasound guided, fine needle puncture from six patients. All six patients had supersaturated bile (mean (SEM) cholesterol saturation index of 1.19 (0.08) (range 1.01-1.53)) and all had abnormally rapid cholesterol microcrystal nucleation times (< 4 days (range 1-4)), whilst in four, the bile contained cholesterol microcrystals immediately after sampling. Of the 12 patients considered for oral ursodeoxycholic acid (UDCA) treatment, two had a blocked cystic duct and were not started on UDCA while one was lost to follow up. After one year of treatment, five of the remaining nine patients showed either partial (n = 3) or complete (n = 2) gall stone dissolution, suggesting that their stones were cholesterol rich. This corresponds, by actuarial (life table) analysis, to a combined gall stone dissolution rate of 58.3 (15.9%). In conclusion, octreotide induced gall stones are generally small, multiple, and cholesterol rich although, in common with spontaneous gall stone disease, at presentation some patients will have a blocked cystic duct and some gall stones containing calcium.","[{'text': 'gall bladder stones', 'type': 'Disease', 'start': 15, 'end': 34, 'mesh': 'D042882'}, {'text': 'octreotide', 'type': 'Chemical', 'start': 51, 'end': 61, 'mesh': 'D015282'}, {'text': 'ursodeoxycholic acid', 'type': 'Chemical', 'start': 80, 'end': 100, 'mesh': 'D014580'}, {'text': 'Octreotide', 'type': 'Chemical', 'start': 102, 'end': 112, 'mesh': 'D015282'}, {'text': 'acromegaly', 'type': 'Disease', 'start': 141, 'end': 151, 'mesh': 'D000172'}, {'text': 'gall bladder stones', 'type': 'Disease', 'start': 161, 'end': 180, 'mesh': 'D042882'}, {'text': 'octreotide', 'type': 'Chemical', 'start': 377, 'end': 387, 'mesh': 'D015282'}, {'text': 'acromegalic', 'type': 'Disease', 'start': 396, 'end': 407, 'mesh': 'D000172'}, {'text': 'gall stones', 'type': 'Disease', 'start': 422, 'end': 433, 'mesh': 'D042882'}, {'text': 'gall stones', 'type': 'Disease', 'start': 456, 'end': 467, 'mesh': 'D042882'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 555, 'end': 566, 'mesh': 'D002784'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 773, 'end': 784, 'mesh': 'D002784'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 958, 'end': 969, 'mesh': 'D002784'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 1050, 'end': 1061, 'mesh': 'D002784'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 1151, 'end': 1162, 'mesh': 'D002784'}, {'text': 'ursodeoxycholic acid', 'type': 'Chemical', 'start': 1244, 'end': 1264, 'mesh': 'D014580'}, {'text': 'UDCA', 'type': 'Chemical', 'start': 1266, 'end': 1270, 'mesh': 'D014580'}, {'text': 'UDCA', 'type': 'Chemical', 'start': 1337, 'end': 1341, 'mesh': 'D014580'}, {'text': 'gall stone', 'type': 'Disease', 'start': 1490, 'end': 1500, 'mesh': 'D042882'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 1548, 'end': 1559, 'mesh': 'D002784'}, {'text': 'gall stone', 'type': 'Disease', 'start': 1634, 'end': 1644, 'mesh': 'D042882'}, {'text': 'octreotide', 'type': 'Chemical', 'start': 1694, 'end': 1704, 'mesh': 'D015282'}, {'text': 'gall stones', 'type': 'Disease', 'start': 1713, 'end': 1724, 'mesh': 'D042882'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 1760, 'end': 1771, 'mesh': 'D002784'}, {'text': 'gall stone disease', 'type': 'Disease', 'start': 1814, 'end': 1832, 'mesh': 'D042882'}, {'text': 'gall stones', 'type': 'Disease', 'start': 1905, 'end': 1916, 'mesh': 'D042882'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1928, 'end': 1935, 'mesh': 'D002118'}]"
+410,7468724,Cardiovascular complications associated with terbutaline treatment for preterm labor.,Severe cardiovascular complications occurred in eight of 160 patients treated with terbutaline for preterm labor. Associated corticosteroid therapy and twin gestations appear to be predisposing factors. Potential mechanisms of the pathophysiology are briefly discussed.,"[{'text': 'Cardiovascular complications', 'type': 'Disease', 'start': 0, 'end': 28, 'mesh': 'D002318'}, {'text': 'terbutaline', 'type': 'Chemical', 'start': 45, 'end': 56, 'mesh': 'D013726'}, {'text': 'preterm labor', 'type': 'Disease', 'start': 71, 'end': 84, 'mesh': 'D007752'}, {'text': 'cardiovascular complications', 'type': 'Disease', 'start': 93, 'end': 121, 'mesh': 'D002318'}, {'text': 'terbutaline', 'type': 'Chemical', 'start': 169, 'end': 180, 'mesh': 'D013726'}, {'text': 'preterm labor', 'type': 'Disease', 'start': 185, 'end': 198, 'mesh': 'D007752'}]"
+411,7199841,"Neurologic effects of subarachnoid administration of 2-chloroprocaine-CE, bupivacaine, and low pH normal saline in dogs.","The purpose of this study was to evaluate the neurologic consequences of deliberate subarachnoid injection of large volumes of 2-chloroprocaine-CE in experimental animals. The possible role of low pH as well as total volume as potential factors in causing neurotoxicity was evaluated. The 65 dogs in the study received injections in the subarachnoid space as follows: 6 to 8 ml of bupivacaine (N = 15), 2-chloroprocaine-CE (N = 20), low pH normal saline (pH 3.0) (N = 20), or normal saline (N = 10). Of the 20 animals that received subarachnoid injection of 2-chloroprocaine-CE seven (35%) developed hind-limb paralysis. None of the animals that received bupivacaine, normal saline, or normal saline titrated to a pH 3.0 developed hind-limb paralysis. Of the 15 spinal cords of the animals that received 2-chloroprocaine-CE, 13 showed subpial necrosis; the nerve roots and subarachnoid vessels were normal. The spinal cords of the animals that received bupivacaine, low pH normal saline (pH 3.0), or normal saline did not show abnormal findings.","[{'text': '2-chloroprocaine-CE', 'type': 'Chemical', 'start': 53, 'end': 72, 'mesh': 'C004616'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 74, 'end': 85, 'mesh': 'D002045'}, {'text': '2-chloroprocaine-CE', 'type': 'Chemical', 'start': 248, 'end': 267, 'mesh': 'C004616'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 377, 'end': 390, 'mesh': 'D020258'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 502, 'end': 513, 'mesh': 'D002045'}, {'text': '2-chloroprocaine-CE', 'type': 'Chemical', 'start': 524, 'end': 543, 'mesh': 'C004616'}, {'text': '2-chloroprocaine-CE', 'type': 'Chemical', 'start': 679, 'end': 698, 'mesh': 'C004616'}, {'text': 'paralysis', 'type': 'Disease', 'start': 731, 'end': 740, 'mesh': 'D010243'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 776, 'end': 787, 'mesh': 'D002045'}, {'text': 'paralysis', 'type': 'Disease', 'start': 862, 'end': 871, 'mesh': 'D010243'}, {'text': '2-chloroprocaine-CE', 'type': 'Chemical', 'start': 925, 'end': 944, 'mesh': 'C004616'}, {'text': 'subpial necrosis', 'type': 'Disease', 'start': 956, 'end': 972, 'mesh': 'D013118'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 1074, 'end': 1085, 'mesh': 'D002045'}]"
+412,6640832,Early adjuvant adriamycin in superficial bladder carcinoma.,"A multicenter study was performed in 110 patients with superficial transitional cell carcinoma of the bladder. Adriamycin (50 mg/50 ml) was administered intravesically within 24 h after transurethral resection of TA-T1 (O-A) bladder tumors. Instillation was repeated twice during the first week, then weekly during the first month and afterwards monthly for 1 year. The tolerance was evaluated in these 110 patients, and 29 patients presented with local side-effects. In 24 of these patients chemical cystitis was severe enough for them to drop out of the study. No systemic side-effects were observed. Recurrence was studied in 82 evaluable patients after 1 year of follow-up and in 72 patients followed for 2-3 years (mean 32 months). Of the 82 patients studied after 1 year, 23 had primary and 59 recurrent disease. Of the 82 evaluable patients, 50 did not show any recurrence after 1 year (61%), while 32 presented with one or more recurrences (39%). Of these recurrences, 27 were T1 tumors while five progressed to more highly invasive lesions. In patients that were free of recurrence during the first year, 80% remained tumor-free during the 2- to 3-year follow-up period. Of the patients developing one or more recurrences during the first year, only 50% presented with further recurrence once the instillations were stopped. The beneficial effect of Adriamycin appears obvious and might be related to the drug itself, the early and repeated instillations after TUR, or both.","[{'text': 'adriamycin', 'type': 'Chemical', 'start': 15, 'end': 25, 'mesh': 'D004317'}, {'text': 'Adriamycin', 'type': 'Chemical', 'start': 171, 'end': 181, 'mesh': 'D004317'}, {'text': 'bladder tumors', 'type': 'Disease', 'start': 285, 'end': 299, 'mesh': 'D001749'}, {'text': 'cystitis', 'type': 'Disease', 'start': 561, 'end': 569, 'mesh': 'D003556'}, {'text': 'tumors', 'type': 'Disease', 'start': 1048, 'end': 1054, 'mesh': 'D009369'}, {'text': 'tumor', 'type': 'Disease', 'start': 1187, 'end': 1192, 'mesh': 'D009369'}, {'text': 'Adriamycin', 'type': 'Chemical', 'start': 1419, 'end': 1429, 'mesh': 'D004317'}]"
+413,3560096,Hyperkalemia associated with sulindac therapy.,"Hyperkalemia has recently been recognized as a complication of nonsteroidal antiinflammatory agents (NSAID) such as indomethacin. Several recent studies have stressed the renal sparing features of sulindac, owing to its lack of interference with renal prostacyclin synthesis. We describe 4 patients in whom hyperkalemia ranging from 6.1 to 6.9 mEq/l developed within 3 to 8 days of sulindac administration. In all of them normal serum potassium levels reached within 2 to 4 days of stopping sulindac. As no other medications known to effect serum potassium had been given concomitantly, this course of events is suggestive of a cause-and-effect relationship between sulindac and hyperkalemia. These observations indicate that initial hopes that sulindac may not be associated with the adverse renal effects of other NSAID are probably not justified.","[{'text': 'Hyperkalemia', 'type': 'Disease', 'start': 0, 'end': 12, 'mesh': 'D006947'}, {'text': 'sulindac', 'type': 'Chemical', 'start': 29, 'end': 37, 'mesh': 'D013467'}, {'text': 'Hyperkalemia', 'type': 'Disease', 'start': 47, 'end': 59, 'mesh': 'D006947'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 163, 'end': 175, 'mesh': 'D007213'}, {'text': 'sulindac', 'type': 'Chemical', 'start': 244, 'end': 252, 'mesh': 'D013467'}, {'text': 'prostacyclin', 'type': 'Chemical', 'start': 299, 'end': 311, 'mesh': 'D011464'}, {'text': 'hyperkalemia', 'type': 'Disease', 'start': 354, 'end': 366, 'mesh': 'D006947'}, {'text': 'sulindac', 'type': 'Chemical', 'start': 429, 'end': 437, 'mesh': 'D013467'}, {'text': 'potassium', 'type': 'Chemical', 'start': 482, 'end': 491, 'mesh': 'D011188'}, {'text': 'sulindac', 'type': 'Chemical', 'start': 538, 'end': 546, 'mesh': 'D013467'}, {'text': 'potassium', 'type': 'Chemical', 'start': 594, 'end': 603, 'mesh': 'D011188'}, {'text': 'sulindac', 'type': 'Chemical', 'start': 713, 'end': 721, 'mesh': 'D013467'}, {'text': 'hyperkalemia', 'type': 'Disease', 'start': 726, 'end': 738, 'mesh': 'D006947'}, {'text': 'sulindac', 'type': 'Chemical', 'start': 792, 'end': 800, 'mesh': 'D013467'}]"
+414,3358181,Ventricular tachyarrhythmias during cesarean section after ritodrine therapy: interaction with anesthetics.,"This case illustrates that patients receiving ritodrine for preterm labor may risk interactions between the residual betamimetic effects of ritodrine and the effects of anesthetics during cesarean section. Such interactions may result in serious cardiovascular complications even after cessation of an infusion of ritodrine. Preoperative assessment should focus on cardiovascular status and serum potassium level. Delaying induction of anesthesia should be considered whenever possible. Careful fluid administration and cautious use of titrated doses of ephedrine are advised. After delivery of the infant, there should be no contraindication to the use of an alpha-adrenergic vasopressor such as phenylephrine to treat hypotensive patients with tachycardia.","[{'text': 'Ventricular tachyarrhythmias', 'type': 'Disease', 'start': 0, 'end': 28, 'mesh': 'D014693'}, {'text': 'ritodrine', 'type': 'Chemical', 'start': 59, 'end': 68, 'mesh': 'D012312'}, {'text': 'ritodrine', 'type': 'Chemical', 'start': 154, 'end': 163, 'mesh': 'D012312'}, {'text': 'preterm labor', 'type': 'Disease', 'start': 168, 'end': 181, 'mesh': 'D007752'}, {'text': 'ritodrine', 'type': 'Chemical', 'start': 248, 'end': 257, 'mesh': 'D012312'}, {'text': 'cardiovascular complications', 'type': 'Disease', 'start': 354, 'end': 382, 'mesh': 'D002318'}, {'text': 'ritodrine', 'type': 'Chemical', 'start': 422, 'end': 431, 'mesh': 'D012312'}, {'text': 'potassium', 'type': 'Chemical', 'start': 505, 'end': 514, 'mesh': 'D011188'}, {'text': 'ephedrine', 'type': 'Chemical', 'start': 662, 'end': 671, 'mesh': 'D004809'}, {'text': 'phenylephrine', 'type': 'Chemical', 'start': 805, 'end': 818, 'mesh': 'D010656'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 828, 'end': 839, 'mesh': 'D007022'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 854, 'end': 865, 'mesh': 'D013610'}]"
+415,2887062,"Immunohistochemical, electron microscopic and morphometric studies of estrogen-induced rat prolactinomas after bromocriptine treatment.","To clarify the effects of bromocriptine on prolactinoma cells in vivo, immunohistochemical, ultrastructural and morphometrical analyses were applied to estrogen-induced rat prolactinoma cells 1 h and 6 h after injection of bromocriptine (3 mg/kg of body weight). One h after treatment, serum prolactin levels decreased markedly. Electron microscopy disclosed many secretory granules, slightly distorted rough endoplasmic reticulum, and partially dilated Golgi cisternae in the prolactinoma cells. Morphometric analysis revealed that the volume density of secretory granules increased, while the volume density of cytoplasmic microtubules decreased. These findings suggest that lowered serum prolactin levels in the early phase of bromocriptine treatment may result from an impaired secretion of prolactin due to decreasing numbers of cytoplasmic microtubules. At 6 h after injection, serum prolactin levels were still considerably lower than in controls. The prolactinoma cells at this time were well granulated, with vesiculated rough endoplasmic reticulum and markedly dilated Golgi cisternae. Electron microscopical immunohistochemistry revealed positive reaction products noted on the secretory granules, Golgi cisternae, and endoplasmic reticulum of the untreated rat prolactinoma cells. However, only secretory granules showed the positive reaction products for prolactin 6 h after bromocriptine treatment of the adenoma cells. An increase in the volume density of secretory granules and a decrease in the volume densities of rough endoplasmic reticulum and microtubules was determined by morphometric analysis, suggesting that bromocriptine inhibits protein synthesis as well as bringing about a disturbance of the prolactin secretion.","[{'text': 'estrogen', 'type': 'Chemical', 'start': 70, 'end': 78, 'mesh': 'D004967'}, {'text': 'prolactinomas', 'type': 'Disease', 'start': 91, 'end': 104, 'mesh': 'D015175'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 111, 'end': 124, 'mesh': 'D001971'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 162, 'end': 175, 'mesh': 'D001971'}, {'text': 'prolactinoma', 'type': 'Disease', 'start': 179, 'end': 191, 'mesh': 'D015175'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 288, 'end': 296, 'mesh': 'D004967'}, {'text': 'prolactinoma', 'type': 'Disease', 'start': 309, 'end': 321, 'mesh': 'D015175'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 359, 'end': 372, 'mesh': 'D001971'}, {'text': 'prolactinoma', 'type': 'Disease', 'start': 613, 'end': 625, 'mesh': 'D015175'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 866, 'end': 879, 'mesh': 'D001971'}, {'text': 'prolactinoma', 'type': 'Disease', 'start': 1095, 'end': 1107, 'mesh': 'D015175'}, {'text': 'prolactinoma', 'type': 'Disease', 'start': 1409, 'end': 1421, 'mesh': 'D015175'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 1524, 'end': 1537, 'mesh': 'D001971'}, {'text': 'adenoma', 'type': 'Disease', 'start': 1555, 'end': 1562, 'mesh': 'D000236'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 1770, 'end': 1783, 'mesh': 'D001971'}]"
+416,2425813,"On two paradoxical side-effects of prednisolone in rats, ribosomal RNA biosyntheses, and a mechanism of action.",Liver enlargement and muscle wastage occurred in Wistar rats following the subcutaneous administration of prednisolone. In the liver both the content of RNA and the biosynthesis of ribosomal RNA increased while both the RNA content and ribosomal RNA biosynthesis were reduced in the gastrocnemius muscle. It is suggested that the drug acted in a selective and tissue-specific manner to enhance ribosomal RNA synthesis in the liver and depress such synthesis in the muscle. This view supports the contention that the liver and muscle are independent sites of prednisolone action.,"[{'text': 'prednisolone', 'type': 'Chemical', 'start': 35, 'end': 47, 'mesh': 'D011239'}, {'text': 'Liver enlargement', 'type': 'Disease', 'start': 112, 'end': 129, 'mesh': 'D006529'}, {'text': 'muscle wastage', 'type': 'Disease', 'start': 134, 'end': 148, 'mesh': 'D009133'}, {'text': 'prednisolone', 'type': 'Chemical', 'start': 218, 'end': 230, 'mesh': 'D011239'}, {'text': 'prednisolone', 'type': 'Chemical', 'start': 670, 'end': 682, 'mesh': 'D011239'}]"
+417,2375138,Possible intramuscular midazolam-associated cardiorespiratory arrest and death.,"Midazolam hydrochloride is commonly used for dental or endoscopic procedures. Although generally consisted safe when given intramuscularly, intravenous administration is known to cause respiratory and cardiovascular depression. This report describes the first published case of cardiorespiratory arrest and death associated with intramuscular administration of midazolam. Information regarding midazolam use is reviewed to provide recommendation for safe administration.","[{'text': 'midazolam', 'type': 'Chemical', 'start': 23, 'end': 32, 'mesh': 'D008874'}, {'text': 'cardiorespiratory arrest', 'type': 'Disease', 'start': 44, 'end': 68, 'mesh': 'D006323'}, {'text': 'death', 'type': 'Disease', 'start': 73, 'end': 78, 'mesh': 'D003643'}, {'text': 'Midazolam hydrochloride', 'type': 'Chemical', 'start': 80, 'end': 103, 'mesh': 'D008874'}, {'text': 'cardiorespiratory arrest', 'type': 'Disease', 'start': 358, 'end': 382, 'mesh': 'D006323'}, {'text': 'death', 'type': 'Disease', 'start': 387, 'end': 392, 'mesh': 'D003643'}, {'text': 'midazolam', 'type': 'Chemical', 'start': 441, 'end': 450, 'mesh': 'D008874'}, {'text': 'midazolam', 'type': 'Chemical', 'start': 474, 'end': 483, 'mesh': 'D008874'}]"
+418,2265898,Serial epilepsy caused by levodopa/carbidopa administration in two patients on hemodialysis.,"Two patients with similar clinical features are presented: both patients had chronic renal failure, on hemodialysis for many years but recently begun on a high-flux dialyzer; both had been receiving a carbidopa/levodopa preparation; and both had the onset of hallucinosis and recurrent seizures, which were refractory to anticonvulsants. The first patient died without a diagnosis; the second patient had a dramatic recovery following the administration of vitamin B6. Neither patient was considered to have a renal state sufficiently severe enough to explain their presentation.","[{'text': 'epilepsy', 'type': 'Disease', 'start': 7, 'end': 15, 'mesh': 'D004827'}, {'text': 'levodopa/carbidopa', 'type': 'Chemical', 'start': 26, 'end': 44, 'mesh': 'C009265'}, {'text': 'chronic renal failure', 'type': 'Disease', 'start': 170, 'end': 191, 'mesh': 'D007676'}, {'text': 'carbidopa/levodopa', 'type': 'Chemical', 'start': 294, 'end': 312, 'mesh': 'C009265'}, {'text': 'hallucinosis', 'type': 'Disease', 'start': 352, 'end': 364, 'mesh': 'D001523'}, {'text': 'seizures', 'type': 'Disease', 'start': 379, 'end': 387, 'mesh': 'D012640'}, {'text': 'vitamin B6', 'type': 'Chemical', 'start': 550, 'end': 560, 'mesh': 'D025101'}]"
+419,2071257,Effect of L-alpha-glyceryl-phosphorylcholine on amnesia caused by scopolamine.,"The present study was carried out to test the effects of L-alpha-glycerylphosphorylcholine (L-alpha-GFC) on memory impairment induced by scopolamine in man. Thirty-two healthy young volunteers were randomly allocated to four different groups. They were given a ten day pretreatment with either L-alpha-GFC or placebo, p.o., and on the eleventh day either scopolamine or placebo, i.m. Before and 0.5, 1, 2, 3, and 6 h after injection the subjects were given attention and mnemonic tests. The findings of this study indicate that the drug is able to antagonize impairment of attention and memory induced by scopolamine.","[{'text': 'L-alpha-glyceryl-phosphorylcholine', 'type': 'Chemical', 'start': 10, 'end': 44, 'mesh': 'D005997'}, {'text': 'amnesia', 'type': 'Disease', 'start': 48, 'end': 55, 'mesh': 'D000647'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 66, 'end': 77, 'mesh': 'D012601'}, {'text': 'L-alpha-glycerylphosphorylcholine', 'type': 'Chemical', 'start': 136, 'end': 169, 'mesh': 'D005997'}, {'text': 'L-alpha-GFC', 'type': 'Chemical', 'start': 171, 'end': 182, 'mesh': 'D005997'}, {'text': 'memory impairment', 'type': 'Disease', 'start': 187, 'end': 204, 'mesh': 'D008569'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 216, 'end': 227, 'mesh': 'D012601'}, {'text': 'L-alpha-GFC', 'type': 'Chemical', 'start': 373, 'end': 384, 'mesh': 'D005997'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 434, 'end': 445, 'mesh': 'D012601'}, {'text': 'impairment of attention and memory', 'type': 'Disease', 'start': 638, 'end': 672, 'mesh': 'D008569'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 684, 'end': 695, 'mesh': 'D012601'}]"
+420,1592014,Seizures induced by the cocaine metabolite benzoylecgonine in rats.,"The half-life (t1/2) of cocaine is relatively short, but some of the consequences of its use, such as seizures and strokes, can occur hours after exposure. This led us to hypothesize that a metabolite of cocaine may be responsible for some of those delayed sequelae. We evaluated the potential of the major metabolite of cocaine, benzoylecgonine (BE), to cause seizures. Two separate equimolar doses (0.2 and 0.4 mumol) of either cocaine or BE were injected ventricularly in unanesthetized juvenile rats. Treated rats were then evaluated for incidence, latency, and seizure pattern or for locomotor activity in animals without seizures. BE-Induced seizures occurred more frequently and had significantly longer latencies than those induced by equimolar amounts of cocaine. Whereas cocaine-induced seizures were best characterized as brief, generalized, and tonic and resulted in death, those induced by BE were prolonged, often multiple and mixed in type, and rarely resulted in death. Electrical recordings from the hippocampus showed a rhythmic progression in EEG frequency and voltage with clinical seizure expression. BE-Injected rats that did not have seizures had significantly more locomotor activity than cocaine-injected animals without seizures. The finding that cocaine- and BE-induced seizures differ in several respects suggests more than one mechanism for cocaine-induced seizures and emphasizes the importance of a cocaine metabolite, BE.","[{'text': 'Seizures', 'type': 'Disease', 'start': 0, 'end': 8, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 24, 'end': 31, 'mesh': 'D003042'}, {'text': 'benzoylecgonine', 'type': 'Chemical', 'start': 43, 'end': 58, 'mesh': 'C005618'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 92, 'end': 99, 'mesh': 'D003042'}, {'text': 'seizures', 'type': 'Disease', 'start': 170, 'end': 178, 'mesh': 'D012640'}, {'text': 'strokes', 'type': 'Disease', 'start': 183, 'end': 190, 'mesh': 'D020521'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 272, 'end': 279, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 389, 'end': 396, 'mesh': 'D003042'}, {'text': 'benzoylecgonine', 'type': 'Chemical', 'start': 398, 'end': 413, 'mesh': 'C005618'}, {'text': 'BE', 'type': 'Chemical', 'start': 415, 'end': 417, 'mesh': 'C005618'}, {'text': 'seizures', 'type': 'Disease', 'start': 429, 'end': 437, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 498, 'end': 505, 'mesh': 'D003042'}, {'text': 'BE', 'type': 'Chemical', 'start': 509, 'end': 511, 'mesh': 'C005618'}, {'text': 'seizure', 'type': 'Disease', 'start': 634, 'end': 641, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 695, 'end': 703, 'mesh': 'D012640'}, {'text': 'BE', 'type': 'Chemical', 'start': 705, 'end': 707, 'mesh': 'C005618'}, {'text': 'seizures', 'type': 'Disease', 'start': 716, 'end': 724, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 832, 'end': 839, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 849, 'end': 856, 'mesh': 'D003042'}, {'text': 'seizures', 'type': 'Disease', 'start': 865, 'end': 873, 'mesh': 'D012640'}, {'text': 'death', 'type': 'Disease', 'start': 947, 'end': 952, 'mesh': 'D003643'}, {'text': 'BE', 'type': 'Chemical', 'start': 971, 'end': 973, 'mesh': 'C005618'}, {'text': 'death', 'type': 'Disease', 'start': 1047, 'end': 1052, 'mesh': 'D003643'}, {'text': 'seizure', 'type': 'Disease', 'start': 1170, 'end': 1177, 'mesh': 'D012640'}, {'text': 'BE', 'type': 'Chemical', 'start': 1190, 'end': 1192, 'mesh': 'C005618'}, {'text': 'seizures', 'type': 'Disease', 'start': 1225, 'end': 1233, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1281, 'end': 1288, 'mesh': 'D003042'}, {'text': 'seizures', 'type': 'Disease', 'start': 1314, 'end': 1322, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1341, 'end': 1348, 'mesh': 'D003042'}, {'text': 'BE', 'type': 'Chemical', 'start': 1354, 'end': 1356, 'mesh': 'C005618'}, {'text': 'seizures', 'type': 'Disease', 'start': 1365, 'end': 1373, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1438, 'end': 1445, 'mesh': 'D003042'}, {'text': 'seizures', 'type': 'Disease', 'start': 1454, 'end': 1462, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1498, 'end': 1505, 'mesh': 'D003042'}, {'text': 'BE', 'type': 'Chemical', 'start': 1518, 'end': 1520, 'mesh': 'C005618'}]"
+421,1436384,"Protection against amphetamine-induced neurotoxicity toward striatal dopamine neurons in rodents by LY274614, an excitatory amino acid antagonist.","LY274614, 3SR,4aRS,6SR,8aRS-6-[phosphonomethyl]decahydr oisoquinoline-3- carboxylic acid, has been described as a potent antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Here its ability to antagonize the prolonged depletion of dopamine in the striatum by amphetamine in iprindole-treated rats is reported. A single 18.4 mg/kg (i.p.) dose of (+/-)-amphetamine hemisulfate, given to rats pretreated with iprindole, resulted in persistent depletion of dopamine in the striatum 1 week later. This prolonged depletion of dopamine in the striatum was antagonized by dizocilpine (MK-801, a non-competitive antagonist of NMDA receptors) or by LY274614 (a competitive antagonist of NMDA receptors). The protective effect of LY274614 was dose-dependent, being maximum at 10-40 mgkg (i.p.). A 10 mg/kg dose of LY274614 was effective in antagonizing the depletion of dopamine in the striatum, when given as long as 8 hr prior to amphetamine but not when given 24 hr prior to amphetamine. Depletion of dopamine in the striatum was also antagonized when LY274614 was given after the injection of amphetamine; LY274614 protected when given up to 4 hr after but not when given 8 or 24 hr after amphetamine. The prolonged depletion of dopamine in the striatum in mice, given multiple injections of methamphetamine, was also antagonized dose-dependently and completely by LY274614. The data strengthen the evidence that the neurotoxic effect of amphetamine and related compounds toward nigrostriatal dopamine neurons involves NMDA receptors and that LY274614 is an NMDA receptor antagonist with long-lasting in vivo effects in rats.","[{'text': 'amphetamine', 'type': 'Chemical', 'start': 19, 'end': 30, 'mesh': 'D000661'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 39, 'end': 52, 'mesh': 'D020258'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 69, 'end': 77, 'mesh': 'D004298'}, {'text': 'LY274614', 'type': 'Chemical', 'start': 100, 'end': 108, 'mesh': 'C070935'}, {'text': 'amino acid', 'type': 'Chemical', 'start': 124, 'end': 134, 'mesh': 'D000596'}, {'text': 'LY274614', 'type': 'Chemical', 'start': 147, 'end': 155, 'mesh': 'C070935'}, {'text': '3SR,4aRS,6SR,8aRS-6-[phosphonomethyl]decahydr oisoquinoline-3- carboxylic acid', 'type': 'Chemical', 'start': 157, 'end': 235, 'mesh': 'C070935'}, {'text': 'N-methyl-D-aspartate', 'type': 'Chemical', 'start': 286, 'end': 306, 'mesh': 'D016202'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 308, 'end': 312, 'mesh': 'D016202'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 325, 'end': 334, 'mesh': 'D018698'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 403, 'end': 411, 'mesh': 'D004298'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 431, 'end': 442, 'mesh': 'D000661'}, {'text': 'iprindole', 'type': 'Chemical', 'start': 446, 'end': 455, 'mesh': 'D007488'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 523, 'end': 534, 'mesh': 'D000661'}, {'text': 'iprindole', 'type': 'Chemical', 'start': 578, 'end': 587, 'mesh': 'D007488'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 625, 'end': 633, 'mesh': 'D004298'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 692, 'end': 700, 'mesh': 'D004298'}, {'text': 'dizocilpine', 'type': 'Chemical', 'start': 736, 'end': 747, 'mesh': 'D016291'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 749, 'end': 755, 'mesh': 'D016291'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 789, 'end': 793, 'mesh': 'D016202'}, {'text': 'LY274614', 'type': 'Chemical', 'start': 811, 'end': 819, 'mesh': 'C070935'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 849, 'end': 853, 'mesh': 'D016202'}, {'text': 'LY274614', 'type': 'Chemical', 'start': 891, 'end': 899, 'mesh': 'C070935'}, {'text': 'LY274614', 'type': 'Chemical', 'start': 975, 'end': 983, 'mesh': 'C070935'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1031, 'end': 1039, 'mesh': 'D004298'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1093, 'end': 1104, 'mesh': 'D000661'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1139, 'end': 1150, 'mesh': 'D000661'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1165, 'end': 1173, 'mesh': 'D004298'}, {'text': 'LY274614', 'type': 'Chemical', 'start': 1216, 'end': 1224, 'mesh': 'C070935'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1258, 'end': 1269, 'mesh': 'D000661'}, {'text': 'LY274614', 'type': 'Chemical', 'start': 1271, 'end': 1279, 'mesh': 'C070935'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1354, 'end': 1365, 'mesh': 'D000661'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1394, 'end': 1402, 'mesh': 'D004298'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 1457, 'end': 1472, 'mesh': 'D008694'}, {'text': 'LY274614', 'type': 'Chemical', 'start': 1530, 'end': 1538, 'mesh': 'C070935'}, {'text': 'neurotoxic', 'type': 'Disease', 'start': 1582, 'end': 1592, 'mesh': 'D020258'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1603, 'end': 1614, 'mesh': 'D000661'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1658, 'end': 1666, 'mesh': 'D004298'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 1684, 'end': 1688, 'mesh': 'D016202'}, {'text': 'LY274614', 'type': 'Chemical', 'start': 1708, 'end': 1716, 'mesh': 'C070935'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 1723, 'end': 1727, 'mesh': 'D016202'}]"
+422,1085609,Neonatal pyridoxine responsive convulsions due to isoniazid therapy.,"A 17-day-old infant on isoniazid therapy 13 mg/kg daily from birth because of maternal tuberculosis was admitted after 4 days of clonic fits. No underlying infective or biochemical cause could be found. The fits ceased within 4 hours of administering intramuscular pyridoxine, suggesting an aetiology of pyridoxine deficiency secondary to isoniazid medication.","[{'text': 'pyridoxine', 'type': 'Chemical', 'start': 9, 'end': 19, 'mesh': 'D011736'}, {'text': 'convulsions', 'type': 'Disease', 'start': 31, 'end': 42, 'mesh': 'D012640'}, {'text': 'isoniazid', 'type': 'Chemical', 'start': 50, 'end': 59, 'mesh': 'D007538'}, {'text': 'isoniazid', 'type': 'Chemical', 'start': 92, 'end': 101, 'mesh': 'D007538'}, {'text': 'tuberculosis', 'type': 'Disease', 'start': 156, 'end': 168, 'mesh': 'D014376'}, {'text': 'clonic fits', 'type': 'Disease', 'start': 198, 'end': 209, 'mesh': 'D012640'}, {'text': 'fits', 'type': 'Disease', 'start': 276, 'end': 280, 'mesh': 'D012640'}, {'text': 'pyridoxine', 'type': 'Chemical', 'start': 334, 'end': 344, 'mesh': 'D011736'}, {'text': 'pyridoxine', 'type': 'Chemical', 'start': 373, 'end': 383, 'mesh': 'D011736'}, {'text': 'isoniazid', 'type': 'Chemical', 'start': 408, 'end': 417, 'mesh': 'D007538'}]"
+423,809711,Reversal by phenylephrine of the beneficial effects of intravenous nitroglycerin in patients with acute myocardial infarction.,"Nitroglycerin has been shown to reduce ST-segment elevation during acute myocardial infarction, an effect potentiated in the dog by agents that reverse nitroglycerin-induced hypotension. Our study was designed to determine the effects of combined nitroglycerin and phenylephrine therapy. Ten patients with acute transmural myocardial infarctions received intravenous nitroglycerin, sufficient to reduce mean arterial pressure from 107 +/- 6 to 85 +/- 6 mm Hg (P less than 0.001), for 60 minutes. Left ventricular filling pressure decreased from 19 +/- 2 to 11 +/- 2 mm Hg (P less than 0.001). SigmaST, the sum of ST-segment elevations in 16 precordial leads, decreased (P less than 0.02) with intravenous nitroglycerin. Subsequent addition of phenylephrine infusion, sufficient to re-elevate mean arterial pressure to 106 +/- 4 mm Hg (P less than 0.001) for 30 minutes, increased left ventricular filling pressure to 17 +/- 2 mm Hg (P less than 0.05) and also significantly increased sigmaST (P less than 0.05). Our results suggest that addition of phenylephrine to nitroglycerin is not beneficial in the treatment of patients with acute myocardial infarction.","[{'text': 'phenylephrine', 'type': 'Chemical', 'start': 12, 'end': 25, 'mesh': 'D010656'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 67, 'end': 80, 'mesh': 'D005996'}, {'text': 'acute myocardial infarction', 'type': 'Disease', 'start': 98, 'end': 125, 'mesh': 'D009203'}, {'text': 'Nitroglycerin', 'type': 'Chemical', 'start': 127, 'end': 140, 'mesh': 'D005996'}, {'text': 'acute myocardial infarction', 'type': 'Disease', 'start': 194, 'end': 221, 'mesh': 'D009203'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 279, 'end': 292, 'mesh': 'D005996'}, {'text': 'hypotension', 'type': 'Disease', 'start': 301, 'end': 312, 'mesh': 'D007022'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 374, 'end': 387, 'mesh': 'D005996'}, {'text': 'phenylephrine', 'type': 'Chemical', 'start': 392, 'end': 405, 'mesh': 'D010656'}, {'text': 'myocardial infarctions', 'type': 'Disease', 'start': 450, 'end': 472, 'mesh': 'D009203'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 494, 'end': 507, 'mesh': 'D005996'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 832, 'end': 845, 'mesh': 'D005996'}, {'text': 'phenylephrine', 'type': 'Chemical', 'start': 870, 'end': 883, 'mesh': 'D010656'}, {'text': 'phenylephrine', 'type': 'Chemical', 'start': 1176, 'end': 1189, 'mesh': 'D010656'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 1193, 'end': 1206, 'mesh': 'D005996'}, {'text': 'acute myocardial infarction', 'type': 'Disease', 'start': 1259, 'end': 1286, 'mesh': 'D009203'}]"
+424,20621845,"Elevation of ADAM10, ADAM17, MMP-2 and MMP-9 expression with media degeneration features CaCl2-induced thoracic aortic aneurysm in a rat model.","PURPOSE: This study was designed to establish a rat model of thoracic aortic aneurysm (TAA) by calcium chloride (CaCl(2))-induced arterial injury and to explore the potential role of a disintegrin and metalloproteinase (ADAM), matrix metalloproteinases (MMPs) and their endogenous inhibitors (TIMPs) in TAA formation. METHODS: Thoracic aorta of male Sprague-Dawley rats was exposed to 0.5M CaCl(2) or normal saline (NaCl). After 12weeks, animals were euthanized, and CaCl(2)-treated, CaCl(2)-untreated (n=12) and NaCl-treated aortic segments (n=12) were collected for histological and molecular assessments. MMP-TIMP and ADAM mRNAs were semi-quantitatively analyzed and protein expressions were determined by immunohistochemistry. RESULTS: Despite similar external diameters among CaCl(2)-treated, non-CaCl(2)-treated and NaCl-treated segments, aneurymal alteration (n=6, 50%), media degeneration with regional disruption, fragmentation of elastic fiber, and increased collagen deposition (n=12, 100%) were demonstrated in CaCl(2)-treated segments. MMP-2, MMP-9, ADAM-10 and ADAM-17 mRNA levels were increased in CaCl(2)-treated segments (all p<0.01), with trends of elevation in CaCl(2)-untreated segments, as compared with NaCl-treated segments. Immunohistochemistry displayed significantly increased expressions of MMP-2, MMP-9, ADAM-10 and ADAM-17 (all p<0.01) in intima and media for CaCl(2)-treated segments. TIMP mRNA and tissue levels did not differ obviously among the three aortic segments. CONCLUSION: This study establishes a TAA model by periarterial CaCl(2) exposure in rats, and demonstrates a significant elevation of expression of MMP-2, MMP-9, ADAM10 and ADAM17 in the pathogenesis of vascular remodeling.","[{'text': 'CaCl2', 'type': 'Chemical', 'start': 89, 'end': 94, 'mesh': 'D002122'}, {'text': 'thoracic aortic aneurysm', 'type': 'Disease', 'start': 103, 'end': 127, 'mesh': 'D017545'}, {'text': 'thoracic aortic aneurysm', 'type': 'Disease', 'start': 205, 'end': 229, 'mesh': 'D017545'}, {'text': 'TAA', 'type': 'Disease', 'start': 231, 'end': 234, 'mesh': 'D017545'}, {'text': 'calcium chloride', 'type': 'Chemical', 'start': 239, 'end': 255, 'mesh': 'D002122'}, {'text': 'CaCl(2)', 'type': 'Chemical', 'start': 257, 'end': 264, 'mesh': 'D002122'}, {'text': 'arterial injury', 'type': 'Disease', 'start': 274, 'end': 289, 'mesh': 'D014652'}, {'text': 'TAA', 'type': 'Disease', 'start': 447, 'end': 450, 'mesh': 'D017545'}, {'text': 'CaCl(2)', 'type': 'Chemical', 'start': 534, 'end': 541, 'mesh': 'D002122'}, {'text': 'NaCl', 'type': 'Chemical', 'start': 560, 'end': 564, 'mesh': 'D012965'}, {'text': 'CaCl(2)', 'type': 'Chemical', 'start': 611, 'end': 618, 'mesh': 'D002122'}, {'text': 'CaCl(2)', 'type': 'Chemical', 'start': 628, 'end': 635, 'mesh': 'D002122'}, {'text': 'NaCl', 'type': 'Chemical', 'start': 657, 'end': 661, 'mesh': 'D012965'}, {'text': 'CaCl(2)', 'type': 'Chemical', 'start': 925, 'end': 932, 'mesh': 'D002122'}, {'text': 'CaCl(2)', 'type': 'Chemical', 'start': 946, 'end': 953, 'mesh': 'D002122'}, {'text': 'NaCl', 'type': 'Chemical', 'start': 966, 'end': 970, 'mesh': 'D012965'}, {'text': 'CaCl(2)', 'type': 'Chemical', 'start': 1167, 'end': 1174, 'mesh': 'D002122'}, {'text': 'CaCl(2)', 'type': 'Chemical', 'start': 1257, 'end': 1264, 'mesh': 'D002122'}, {'text': 'CaCl(2)', 'type': 'Chemical', 'start': 1324, 'end': 1331, 'mesh': 'D002122'}, {'text': 'NaCl', 'type': 'Chemical', 'start': 1369, 'end': 1373, 'mesh': 'D012965'}, {'text': 'CaCl(2)', 'type': 'Chemical', 'start': 1533, 'end': 1540, 'mesh': 'D002122'}, {'text': 'TAA', 'type': 'Disease', 'start': 1682, 'end': 1685, 'mesh': 'D017545'}, {'text': 'CaCl(2)', 'type': 'Chemical', 'start': 1708, 'end': 1715, 'mesh': 'D002122'}]"
+425,19843802,When drugs disappear from the patient: elimination of intravenous medication by hemodiafiltration.,"Twenty-three hours after heart transplantation, life-threatening acute right heart failure was diagnosed in a patient requiring continuous venovenous hemodiafiltration (CVVHDF). Increasing doses of catecholamines, sedatives, and muscle relaxants administered through a central venous catheter were ineffective. However, a bolus of epinephrine injected through an alternative catheter provoked a hypertensive crisis. Thus, interference with the central venous infusion by the dialysis catheter was suspected. The catheters were changed, and hemodynamics stabilized at lower catecholamine doses. When the effects of IV drugs are inadequate in patients receiving CVVHDF, interference with adjacent catheters resulting in elimination of the drug by CVVHDF should be suspected.","[{'text': 'right heart failure', 'type': 'Disease', 'start': 170, 'end': 189, 'mesh': 'D006333'}, {'text': 'catecholamines', 'type': 'Chemical', 'start': 297, 'end': 311, 'mesh': 'D002395'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 430, 'end': 441, 'mesh': 'D004837'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 494, 'end': 506, 'mesh': 'D006973'}, {'text': 'catecholamine', 'type': 'Chemical', 'start': 672, 'end': 685, 'mesh': 'D002395'}]"
+426,19473225,Long-term glutamate supplementation failed to protect against peripheral neurotoxicity of paclitaxel.,"Toxic peripheral neuropathy is still a significant limiting factor for chemotherapy with paclitaxel (PAC), although glutamate and its closely related amino acid glutamine were claimed to ameliorate PAC neurotoxicity. This pilot trial aimed to evaluate the role of glutamate supplementation for preventing PAC-induced peripheral neuropathy in a randomized, placebo-controlled, double-blinded clinical and electro-diagnostic study. Forty-three ovarian cancer patients were available for analysis following six cycles of the same PAC-containing regimen: 23 had been supplemented by glutamate all along the treatment period, at a daily dose of three times 500 mg (group G), and 20 had received a placebo (group P). Patients were evaluated by neurological examinations, questionnaires and sensory-motor nerve conduction studies. There was no significant difference in the frequency of signs or symptoms between the two groups although neurotoxicity symptoms presented mostly with lower scores of severity in group G. However, this difference reached statistical significance only with regard to reported pain sensation (P = 0.011). Also the frequency of abnormal electro-diagnostic findings showed similarity between the two groups (G: 7/23 = 30.4%; P: 6/20 = 30%). This pilot study leads to the conclusion that glutamate supplementation at the chosen regimen fails to protect against peripheral neurotoxicity of PAC.","[{'text': 'glutamate', 'type': 'Chemical', 'start': 10, 'end': 19, 'mesh': 'D018698'}, {'text': 'peripheral neurotoxicity', 'type': 'Disease', 'start': 62, 'end': 86, 'mesh': 'D010523'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 90, 'end': 100, 'mesh': 'D017239'}, {'text': 'peripheral neuropathy', 'type': 'Disease', 'start': 108, 'end': 129, 'mesh': 'D010523'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 191, 'end': 201, 'mesh': 'D017239'}, {'text': 'PAC', 'type': 'Chemical', 'start': 203, 'end': 206, 'mesh': 'D017239'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 218, 'end': 227, 'mesh': 'D018698'}, {'text': 'amino acid', 'type': 'Chemical', 'start': 252, 'end': 262, 'mesh': 'D000596'}, {'text': 'glutamine', 'type': 'Chemical', 'start': 263, 'end': 272, 'mesh': 'D018698'}, {'text': 'PAC', 'type': 'Chemical', 'start': 300, 'end': 303, 'mesh': 'D017239'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 304, 'end': 317, 'mesh': 'D020258'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 366, 'end': 375, 'mesh': 'D018698'}, {'text': 'PAC', 'type': 'Chemical', 'start': 407, 'end': 410, 'mesh': 'D017239'}, {'text': 'peripheral neuropathy', 'type': 'Disease', 'start': 419, 'end': 440, 'mesh': 'D010523'}, {'text': 'ovarian cancer', 'type': 'Disease', 'start': 544, 'end': 558, 'mesh': 'D010051'}, {'text': 'PAC', 'type': 'Chemical', 'start': 629, 'end': 632, 'mesh': 'D017239'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 681, 'end': 690, 'mesh': 'D018698'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 1032, 'end': 1045, 'mesh': 'D020258'}, {'text': 'pain', 'type': 'Disease', 'start': 1201, 'end': 1205, 'mesh': 'D010146'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 1409, 'end': 1418, 'mesh': 'D018698'}, {'text': 'peripheral neurotoxicity', 'type': 'Disease', 'start': 1482, 'end': 1506, 'mesh': 'D010523'}, {'text': 'PAC', 'type': 'Chemical', 'start': 1510, 'end': 1513, 'mesh': 'D017239'}]"
+427,19387625,Attentional modulation of perceived pain intensity in capsaicin-induced secondary hyperalgesia.,"Perceived pain intensity is modulated by attention. However, it is not known that how pain intensity ratings are affected by attention in capsaicin-induced secondary hyperalgesia. Here we show that perceived pain intensity in secondary hyperalgesia is decreased when attention is distracted away from the painful pinprick stimulus with a visual task. Furthermore, it was found that the magnitude of attentional modulation in secondary hyperalgesia is very similar to that of capsaicin-untreated, control condition. Our findings, showing no interaction between capsaicin treatment and attentional modulation suggest that capsaicin-induced secondary hyperalgesia and attention might affect mechanical pain through independent mechanisms.","[{'text': 'pain', 'type': 'Disease', 'start': 36, 'end': 40, 'mesh': 'D010146'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 54, 'end': 63, 'mesh': 'D002211'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 82, 'end': 94, 'mesh': 'D006930'}, {'text': 'pain', 'type': 'Disease', 'start': 106, 'end': 110, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 182, 'end': 186, 'mesh': 'D010146'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 234, 'end': 243, 'mesh': 'D002211'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 262, 'end': 274, 'mesh': 'D006930'}, {'text': 'pain', 'type': 'Disease', 'start': 304, 'end': 308, 'mesh': 'D010146'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 332, 'end': 344, 'mesh': 'D006930'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 531, 'end': 543, 'mesh': 'D006930'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 571, 'end': 580, 'mesh': 'D002211'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 656, 'end': 665, 'mesh': 'D002211'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 716, 'end': 725, 'mesh': 'D002211'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 744, 'end': 756, 'mesh': 'D006930'}, {'text': 'pain', 'type': 'Disease', 'start': 795, 'end': 799, 'mesh': 'D010146'}]"
+428,19211690,Testosterone-dependent hypertension and upregulation of intrarenal angiotensinogen in Dahl salt-sensitive rats.,"Blood pressure (BP) is more salt sensitive in men than in premenopausal women. In Dahl salt-sensitive rats (DS), high-salt (HS) diet increases BP more in males than females. In contrast to the systemic renin-angiotensin system, which is suppressed in response to HS in male DS, intrarenal angiotensinogen expression is increased, and intrarenal levels of ANG II are not suppressed. In this study, the hypothesis was tested that there is a sexual dimorphism in HS-induced upregulation of intrarenal angiotensinogen mediated by testosterone that also causes increases in BP and renal injury. On a low-salt (LS) diet, male DS had higher levels of intrarenal angiotensinogen mRNA than females. HS diet for 4 wk increased renal cortical angiotensinogen mRNA and protein only in male DS, which was prevented by castration. Ovariectomy of female DS had no effect on intrarenal angiotensinogen expression on either diet. Radiotelemetric BP was similar between males and castrated rats on LS diet. HS diet for 4 wk caused a progressive increase in BP, protein and albumin excretion, and glomerular sclerosis in male DS rats, which were attenuated by castration. Testosterone replacement in castrated DS rats increased BP, renal injury, and upregulation of renal angiotensinogen associated with HS diet. Testosterone contributes to the development of hypertension and renal injury in male DS rats on HS diet possibly through upregulation of the intrarenal renin-angiotensin system.","[{'text': 'Testosterone', 'type': 'Chemical', 'start': 0, 'end': 12, 'mesh': 'D013739'}, {'text': 'hypertension', 'type': 'Disease', 'start': 23, 'end': 35, 'mesh': 'D006973'}, {'text': 'salt', 'type': 'Chemical', 'start': 91, 'end': 95, 'mesh': 'D017673'}, {'text': 'salt', 'type': 'Chemical', 'start': 140, 'end': 144, 'mesh': 'D017673'}, {'text': 'salt', 'type': 'Chemical', 'start': 199, 'end': 203, 'mesh': 'D017673'}, {'text': 'salt', 'type': 'Chemical', 'start': 230, 'end': 234, 'mesh': 'D017673'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 320, 'end': 331, 'mesh': 'D000809'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 638, 'end': 650, 'mesh': 'D013739'}, {'text': 'renal injury', 'type': 'Disease', 'start': 688, 'end': 700, 'mesh': 'D007674'}, {'text': 'salt', 'type': 'Chemical', 'start': 711, 'end': 715, 'mesh': 'D017673'}, {'text': 'glomerular sclerosis', 'type': 'Disease', 'start': 1190, 'end': 1210, 'mesh': 'D007674'}, {'text': 'Testosterone', 'type': 'Chemical', 'start': 1265, 'end': 1277, 'mesh': 'D013739'}, {'text': 'renal injury', 'type': 'Disease', 'start': 1325, 'end': 1337, 'mesh': 'D007674'}, {'text': 'Testosterone', 'type': 'Chemical', 'start': 1406, 'end': 1418, 'mesh': 'D013739'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1453, 'end': 1465, 'mesh': 'D006973'}, {'text': 'renal injury', 'type': 'Disease', 'start': 1470, 'end': 1482, 'mesh': 'D007674'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 1564, 'end': 1575, 'mesh': 'D000809'}]"
+429,18703024,Prenatal protein deprivation alters dopamine-mediated behaviors and dopaminergic and glutamatergic receptor binding.,"Epidemiological evidence indicates that prenatal nutritional deprivation may increase the risk of schizophrenia. The goal of these studies was to use an animal model to examine the effects of prenatal protein deprivation on behaviors and receptor binding with relevance to schizophrenia. We report that prenatally protein deprived (PD) female rats showed an increased stereotypic response to apomorphine and an increased locomotor response to amphetamine in adulthood. These differences were not observed during puberty. No changes in haloperidol-induced catalepsy or MK-801-induced locomotion were seen following PD. In addition, PD female rats showed increased (3)H-MK-801 binding in the striatum and hippocampus, but not in the cortex. PD female rats also showed increased (3)H-haloperidol binding and decreased dopamine transporter binding in striatum. No statistically significant changes in behavior or receptor binding were found in PD males with the exception of increased (3)H-MK-801 binding in cortex. This animal model may be useful to explore the mechanisms by which prenatal nutritional deficiency enhances risk for schizophrenia in humans and may also have implications for developmental processes leading to differential sensitivity to drugs of abuse.","[{'text': 'dopamine', 'type': 'Chemical', 'start': 36, 'end': 44, 'mesh': 'D004298'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 215, 'end': 228, 'mesh': 'D012559'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 390, 'end': 403, 'mesh': 'D012559'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 509, 'end': 520, 'mesh': 'D001058'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 560, 'end': 571, 'mesh': 'D000661'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 652, 'end': 663, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 672, 'end': 681, 'mesh': 'D002375'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 685, 'end': 691, 'mesh': 'D016291'}, {'text': 'H', 'type': 'Chemical', 'start': 783, 'end': 784, 'mesh': 'D006859'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 785, 'end': 791, 'mesh': 'D016291'}, {'text': 'H', 'type': 'Chemical', 'start': 896, 'end': 897, 'mesh': 'D006859'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 898, 'end': 909, 'mesh': 'D006220'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 932, 'end': 940, 'mesh': 'D004298'}, {'text': 'H', 'type': 'Chemical', 'start': 1101, 'end': 1102, 'mesh': 'D006859'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 1103, 'end': 1109, 'mesh': 'D016291'}, {'text': 'nutritional deficiency', 'type': 'Disease', 'start': 1205, 'end': 1227, 'mesh': 'D044342'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 1246, 'end': 1259, 'mesh': 'D012559'}]"
+430,18631865,"mToR inhibitors-induced proteinuria: mechanisms, significance, and management.","Massive urinary protein excretion has been observed after conversion from calcineurin inhibitors to mammalian target of rapamycin (mToR) inhibitors, especially sirolimus, in renal transplant recipients with chronic allograft nephropathy. Because proteinuria is a major predictive factor of poor transplantation outcome, many studies focused on this adverse event during the past years. Whether proteinuria was due to sirolimus or only a consequence of calcineurin inhibitors withdrawal remained unsolved until high range proteinuria has been observed during sirolimus therapy in islet transplantation and in patients who received sirolimus de novo. Podocyte injury and focal segmental glomerulosclerosis have been related to mToR inhibition in some patients, but the pathways underlying these lesions remain hypothetic. We discuss herein the possible mechanisms and the significance of mToR blockade-induced proteinuria.","[{'text': 'proteinuria', 'type': 'Disease', 'start': 24, 'end': 35, 'mesh': 'D011507'}, {'text': 'rapamycin', 'type': 'Chemical', 'start': 199, 'end': 208, 'mesh': 'D020123'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 239, 'end': 248, 'mesh': 'D020123'}, {'text': 'chronic allograft nephropathy', 'type': 'Disease', 'start': 286, 'end': 315, 'mesh': 'D051436'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 325, 'end': 336, 'mesh': 'D011507'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 473, 'end': 484, 'mesh': 'D011507'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 496, 'end': 505, 'mesh': 'D020123'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 600, 'end': 611, 'mesh': 'D011507'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 637, 'end': 646, 'mesh': 'D020123'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 709, 'end': 718, 'mesh': 'D020123'}, {'text': 'glomerulosclerosis', 'type': 'Disease', 'start': 764, 'end': 782, 'mesh': 'D005921'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 987, 'end': 998, 'mesh': 'D011507'}]"
+431,18162529,"Hypothalamic prolactin receptor messenger ribonucleic acid levels, prolactin signaling, and hyperprolactinemic inhibition of pulsatile luteinizing hormone secretion are dependent on estradiol.","Hyperprolactinemia can reduce fertility and libido. Although central prolactin actions are thought to contribute to this, the mechanisms are poorly understood. We first tested whether chronic hyperprolactinemia inhibited two neuroendocrine parameters necessary for female fertility: pulsatile LH secretion and the estrogen-induced LH surge. Chronic hyperprolactinemia induced by the dopamine antagonist sulpiride caused a 40% reduction LH pulse frequency in ovariectomized rats, but only in the presence of chronic low levels of estradiol. Sulpiride did not affect the magnitude of a steroid-induced LH surge or the percentage of GnRH neurons activated during the surge. Estradiol is known to influence expression of the long form of prolactin receptors (PRL-R) and components of prolactin's signaling pathway. To test the hypothesis that estrogen increases PRL-R expression and sensitivity to prolactin, we next demonstrated that estradiol greatly augments prolactin-induced STAT5 activation. Lastly, we measured PRL-R and suppressor of cytokine signaling (SOCS-1 and -3 and CIS, which reflect the level of prolactin signaling) mRNAs in response to sulpiride and estradiol. Sulpiride induced only SOCS-1 in the medial preoptic area, where GnRH neurons are regulated, but in the arcuate nucleus and choroid plexus, PRL-R, SOCS-3, and CIS mRNA levels were also induced. Estradiol enhanced these effects on SOCS-3 and CIS. Interestingly, estradiol also induced PRL-R, SOCS-3, and CIS mRNA levels independently. These data show that GnRH pulse frequency is inhibited by chronic hyperprolactinemia in a steroid-dependent manner. They also provide evidence for estradiol-dependent and brain region-specific regulation of PRL-R expression and signaling responses by prolactin.","[{'text': 'ribonucleic acid', 'type': 'Chemical', 'start': 42, 'end': 58, 'mesh': 'D012313'}, {'text': 'hyperprolactinemic', 'type': 'Disease', 'start': 92, 'end': 110, 'mesh': 'D006966'}, {'text': 'estradiol', 'type': 'Chemical', 'start': 182, 'end': 191, 'mesh': 'D004958'}, {'text': 'Hyperprolactinemia', 'type': 'Disease', 'start': 193, 'end': 211, 'mesh': 'D006966'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 385, 'end': 403, 'mesh': 'D006966'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 507, 'end': 515, 'mesh': 'D004967'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 542, 'end': 560, 'mesh': 'D006966'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 576, 'end': 584, 'mesh': 'D004298'}, {'text': 'sulpiride', 'type': 'Chemical', 'start': 596, 'end': 605, 'mesh': 'D013469'}, {'text': 'estradiol', 'type': 'Chemical', 'start': 722, 'end': 731, 'mesh': 'D004958'}, {'text': 'Sulpiride', 'type': 'Chemical', 'start': 733, 'end': 742, 'mesh': 'D013469'}, {'text': 'steroid', 'type': 'Chemical', 'start': 777, 'end': 784, 'mesh': 'D013256'}, {'text': 'Estradiol', 'type': 'Chemical', 'start': 864, 'end': 873, 'mesh': 'D004958'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 1032, 'end': 1040, 'mesh': 'D004967'}, {'text': 'estradiol', 'type': 'Chemical', 'start': 1124, 'end': 1133, 'mesh': 'D004958'}, {'text': 'sulpiride', 'type': 'Chemical', 'start': 1343, 'end': 1352, 'mesh': 'D013469'}, {'text': 'estradiol', 'type': 'Chemical', 'start': 1357, 'end': 1366, 'mesh': 'D004958'}, {'text': 'Sulpiride', 'type': 'Chemical', 'start': 1368, 'end': 1377, 'mesh': 'D013469'}, {'text': 'Estradiol', 'type': 'Chemical', 'start': 1562, 'end': 1571, 'mesh': 'D004958'}, {'text': 'estradiol', 'type': 'Chemical', 'start': 1629, 'end': 1638, 'mesh': 'D004958'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 1768, 'end': 1786, 'mesh': 'D006966'}, {'text': 'steroid', 'type': 'Chemical', 'start': 1792, 'end': 1799, 'mesh': 'D013256'}, {'text': 'estradiol', 'type': 'Chemical', 'start': 1849, 'end': 1858, 'mesh': 'D004958'}]"
+432,17879945,Estrogen prevents cholesteryl ester accumulation in macrophages induced by the HIV protease inhibitor ritonavir.,"Individuals with HIV can now live long lives with drug therapy that often includes protease inhibitors such as ritonavir. Many patients, however, develop negative long-term side effects such as premature atherosclerosis. We have previously demonstrated that ritonavir treatment increases atherosclerotic lesion formation in male mice to a greater extent than in female mice. Furthermore, peripheral blood monocytes isolated from ritonavir-treated females had less cholesteryl ester accumulation. In the present study, we have investigated the molecular mechanisms by which female hormones influence cholesterol metabolism in macrophages in response to the HIV protease inhibitor ritonavir. We have utilized the human monocyte cell line, THP-1 as a model to address this question. Briefly, cells were differentiated for 72 h with 100 nM PMA to obtain a macrophage-like phenotype in the presence or absence of 1 nM 17beta-estradiol (E2), 100 nM progesterone or vehicle (0.01% ethanol). Cells were then treated with 30 ng/ml ritonavir or vehicle in the presence of aggregated LDL for 24 h. Cell extracts were harvested, and lipid or total RNA was isolated. E2 decreased the accumulation of cholesteryl esters in macrophages following ritonavir treatment. Ritonavir increased the expression of the scavenger receptor, CD36 mRNA, responsible for the uptake of LDL. Additionally, ritonavir treatment selectively increased the relative levels of PPARgamma mRNA, a transcription factor responsible for the regulation of CD36 mRNA expression. Treatment with E2, however, failed to prevent these increases at the mRNA level. E2 did, however, significantly suppress CD36 protein levels as measured by fluorescent immunocytochemistry. This data suggests that E2 modifies the expression of CD36 at the level of protein expression in monocyte-derived macrophages resulting in reduced cholesteryl ester accumulation following ritonavir treatment.","[{'text': 'cholesteryl ester', 'type': 'Chemical', 'start': 18, 'end': 35, 'mesh': 'D002788'}, {'text': 'ritonavir', 'type': 'Chemical', 'start': 102, 'end': 111, 'mesh': 'D019438'}, {'text': 'ritonavir', 'type': 'Chemical', 'start': 224, 'end': 233, 'mesh': 'D019438'}, {'text': 'premature atherosclerosis', 'type': 'Disease', 'start': 307, 'end': 332, 'mesh': 'D050197'}, {'text': 'ritonavir', 'type': 'Chemical', 'start': 371, 'end': 380, 'mesh': 'D019438'}, {'text': 'atherosclerotic lesion', 'type': 'Disease', 'start': 401, 'end': 423, 'mesh': 'D050197'}, {'text': 'ritonavir', 'type': 'Chemical', 'start': 542, 'end': 551, 'mesh': 'D019438'}, {'text': 'cholesteryl ester', 'type': 'Chemical', 'start': 577, 'end': 594, 'mesh': 'D002788'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 712, 'end': 723, 'mesh': 'D002784'}, {'text': 'ritonavir', 'type': 'Chemical', 'start': 792, 'end': 801, 'mesh': 'D019438'}, {'text': '17beta-estradiol', 'type': 'Chemical', 'start': 1026, 'end': 1042, 'mesh': 'D004958'}, {'text': 'E2', 'type': 'Chemical', 'start': 1044, 'end': 1046, 'mesh': 'D004958'}, {'text': 'progesterone', 'type': 'Chemical', 'start': 1056, 'end': 1068, 'mesh': 'D011374'}, {'text': 'ethanol', 'type': 'Chemical', 'start': 1087, 'end': 1094, 'mesh': 'D000431'}, {'text': 'ritonavir', 'type': 'Chemical', 'start': 1135, 'end': 1144, 'mesh': 'D019438'}, {'text': 'E2', 'type': 'Chemical', 'start': 1267, 'end': 1269, 'mesh': 'D004958'}, {'text': 'cholesteryl esters', 'type': 'Chemical', 'start': 1300, 'end': 1318, 'mesh': 'D002788'}, {'text': 'ritonavir', 'type': 'Chemical', 'start': 1344, 'end': 1353, 'mesh': 'D019438'}, {'text': 'Ritonavir', 'type': 'Chemical', 'start': 1365, 'end': 1374, 'mesh': 'D019438'}, {'text': 'ritonavir', 'type': 'Chemical', 'start': 1487, 'end': 1496, 'mesh': 'D019438'}, {'text': 'E2', 'type': 'Chemical', 'start': 1662, 'end': 1664, 'mesh': 'D004958'}, {'text': 'E2', 'type': 'Chemical', 'start': 1728, 'end': 1730, 'mesh': 'D004958'}, {'text': 'E2', 'type': 'Chemical', 'start': 1860, 'end': 1862, 'mesh': 'D004958'}, {'text': 'cholesteryl ester', 'type': 'Chemical', 'start': 1983, 'end': 2000, 'mesh': 'D002788'}, {'text': 'ritonavir', 'type': 'Chemical', 'start': 2024, 'end': 2033, 'mesh': 'D019438'}]"
+433,17437408,Upregulation of brain expression of P-glycoprotein in MRP2-deficient TR(-) rats resembles seizure-induced up-regulation of this drug efflux transporter in normal rats.,"PURPOSE: The multidrug resistance protein 2 (MRP2) is a drug efflux transporter that is expressed predominantly at the apical domain of hepatocytes but seems also to be expressed at the apical membrane of brain capillary endothelial cells that form the blood-brain barrier (BBB). MRP2 is absent in the transport-deficient (TR(-)) Wistar rat mutant, so that this rat strain was very helpful in defining substrates of MRP2 by comparing tissue concentrations or functional activities of compounds in MRP2-deficient rats with those in transport-competent Wistar rats. By using this strategy to study the involvement of MRP2 in brain access of antiepileptic drugs (AEDs), we recently reported that phenytoin is a substrate for MRP2 in the BBB. However, one drawback of such studies in genetically deficient rats is the fact that compensatory changes with upregulation of other transporters can occur. This prompted us to study the brain expression of P-glycoprotein (Pgp), a major drug efflux transporter in many tissues, including the BBB, in TR(-) rats compared with nonmutant (wild-type) Wistar rats. METHODS: The expression of MRP2 and Pgp in brain and liver sections of TR(-) rats and normal Wistar rats was determined with immunohistochemistry, by using a novel, highly selective monoclonal MRP2 antibody and the monoclonal Pgp antibody C219, respectively. RESULTS: Immunofluorescence staining with the MRP2 antibody was found to label a high number of microvessels throughout the brain in normal Wistar rats, whereas such labeling was absent in TR(-) rats. TR(-) rats exhibited a significant up-regulation of Pgp in brain capillary endothelial cells compared with wild-type controls. No such obvious upregulation of Pgp was observed in liver sections. A comparable overexpression of Pgp in the BBB was obtained after pilocarpine-induced seizures in wild-type Wistar rats. Experiments with systemic administration of the Pgp substrate phenobarbital and the selective Pgp inhibitor tariquidar in TR(-) rats substantiated that Pgp is functional and compensates for the lack of MRP2 in the BBB. CONCLUSIONS: The data on TR(-) rats indicate that Pgp plays an important role in the compensation of MRP2 deficiency in the BBB. Because such a compensatory mechanism most likely occurs to reduce injury to the brain from cytotoxic compounds, the present data substantiate the concept that MRP2 performs a protective role in the BBB. Furthermore, our data suggest that TR(-) rats are an interesting tool to study consequences of overexpression of Pgp in the BBB on access of drugs in the brain, without the need of inducing seizures or other Pgp-enhancing events for this purpose.","[{'text': 'seizure', 'type': 'Disease', 'start': 90, 'end': 97, 'mesh': 'D012640'}, {'text': 'phenytoin', 'type': 'Chemical', 'start': 861, 'end': 870, 'mesh': 'D010672'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1987, 'end': 1998, 'mesh': 'D010862'}, {'text': 'seizures', 'type': 'Disease', 'start': 2007, 'end': 2015, 'mesh': 'D012640'}, {'text': 'phenobarbital', 'type': 'Chemical', 'start': 2104, 'end': 2117, 'mesh': 'D010634'}, {'text': 'tariquidar', 'type': 'Chemical', 'start': 2150, 'end': 2160, 'mesh': 'C402343'}, {'text': 'injury to the brain', 'type': 'Disease', 'start': 2457, 'end': 2476, 'mesh': 'D001927'}, {'text': 'seizures', 'type': 'Disease', 'start': 2784, 'end': 2792, 'mesh': 'D012640'}]"
+434,17242861,Use of chromosome substitution strains to identify seizure susceptibility loci in mice.,"Seizure susceptibility varies among inbred mouse strains. Chromosome substitution strains (CSS), in which a single chromosome from one inbred strain (donor) has been transferred onto a second strain (host) by repeated backcrossing, may be used to identify quantitative trait loci (QTLs) that contribute to seizure susceptibility. QTLs for susceptibility to pilocarpine-induced seizures, a model of temporal lobe epilepsy, have not been reported, and CSS have not previously been used to localize seizure susceptibility genes. We report QTLs identified using a B6 (host) x A/J (donor) CSS panel to localize genes involved in susceptibility to pilocarpine-induced seizures. Three hundred fifty-five adult male CSS mice, 58 B6, and 39 A/J were tested for susceptibility to pilocarpine-induced seizures. Highest stage reached and latency to each stage were recorded for all mice. B6 mice were resistant to seizures and slower to reach stages compared to A/J mice. The CSS for Chromosomes 10 and 18 progressed to the most severe stages, diverging dramatically from the B6 phenotype. Latencies to stages were also significantly shorter for CSS10 and CSS18 mice. CSS mapping suggests seizure susceptibility loci on mouse Chromosomes 10 and 18. This approach provides a framework for identifying potentially novel homologous candidate genes for human temporal lobe epilepsy.","[{'text': 'seizure', 'type': 'Disease', 'start': 51, 'end': 58, 'mesh': 'D012640'}, {'text': 'Seizure', 'type': 'Disease', 'start': 88, 'end': 95, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 394, 'end': 401, 'mesh': 'D012640'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 445, 'end': 456, 'mesh': 'D010862'}, {'text': 'seizures', 'type': 'Disease', 'start': 465, 'end': 473, 'mesh': 'D012640'}, {'text': 'temporal lobe epilepsy', 'type': 'Disease', 'start': 486, 'end': 508, 'mesh': 'D004833'}, {'text': 'seizure', 'type': 'Disease', 'start': 584, 'end': 591, 'mesh': 'D012640'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 730, 'end': 741, 'mesh': 'D010862'}, {'text': 'seizures', 'type': 'Disease', 'start': 750, 'end': 758, 'mesh': 'D012640'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 858, 'end': 869, 'mesh': 'D010862'}, {'text': 'seizures', 'type': 'Disease', 'start': 878, 'end': 886, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 990, 'end': 998, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 1265, 'end': 1272, 'mesh': 'D012640'}, {'text': 'temporal lobe epilepsy', 'type': 'Disease', 'start': 1431, 'end': 1453, 'mesh': 'D004833'}]"
+435,16337777,Investigation of mitochondrial involvement in the experimental model of epilepsy induced by pilocarpine.,"Mitochondrial abnormalities have been associated with several aspects of epileptogenesis, such as energy generation, control of cell death, neurotransmitter synthesis, and free radical (FR) production. Increased production of FRs may cause mtDNA damage leading to decreased activities of oxidative phosphorylation complexes containing mtDNA-encoded subunits. In this study, we investigated whether increased generation of FR during status epilepticus would be sufficient to provoke abnormalities in mtDNA and in the expression and activity of cytochrome c oxidase (CCO), complex IV of the respiratory chain, in the chronic phase of the pilocarpine model of temporal lobe epilepsy. DNA analysis revealed low amounts of a 4.8 kb mtDNA deletion but with no differences in frequency or quantity in the control and experimental groups. We did not find abnormalities in the expression and distribution of an mtDNA-encoded subunit of CCO (CCO-I) or a relative decrease in CCO-I when compared with nuclear-encoded subunits (CCO-IV and SDH-fp). No abnormality in CCO activity was observed through histochemistry. Although evidences of mitochondrial abnormalities were found in previously published studies, our results do not suggest that the FRs, generated during the acute phase, determined important abnormalities in mtDNA, in expression of CCO-I, and in CCO activity.","[{'text': 'epilepsy', 'type': 'Disease', 'start': 72, 'end': 80, 'mesh': 'D004827'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 92, 'end': 103, 'mesh': 'D010862'}, {'text': 'Mitochondrial abnormalities', 'type': 'Disease', 'start': 105, 'end': 132, 'mesh': 'D028361'}, {'text': 'death', 'type': 'Disease', 'start': 238, 'end': 243, 'mesh': 'D003643'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 537, 'end': 555, 'mesh': 'D013226'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 741, 'end': 752, 'mesh': 'D010862'}, {'text': 'temporal lobe epilepsy', 'type': 'Disease', 'start': 762, 'end': 784, 'mesh': 'D004833'}, {'text': 'mitochondrial abnormalities', 'type': 'Disease', 'start': 1231, 'end': 1258, 'mesh': 'D028361'}]"
+436,15859940,Causes of acute thrombotic microangiopathy in patients receiving kidney transplantation.,"OBJECTIVES: Thrombotic microangiopathy is a well-known problem in patients following renal transplantation. In postrenal transplantation, thrombotic microangiopathy is often a reflection of hemolytic uremic syndrome. We aimed to determine the causes of thrombotic microangiopathy in a population of renal transplantation recipients and discuss the literature. MATERIALS AND METHODS: We investigated the causes of thrombotic microangiopathy during a 1-year period, from June 2003 to June 2004, at the King Fahad National Guard Hospital in Riyadh, Saudi Arabia, by reviewing the slides of all transplant biopsies (n=25) performed during this interval. Pre- and posttransplant crossmatching was done when possible. RESULTS: Five cases of thrombotic microangiopathy were found. Three of these cases were from the 25 transplantations performed at King Fahad National Guard Hospital, while the other 2 transplantations had been performed abroad and were referred to us for follow-up. Three cases were related to cyclosporine, and 1 case was secondary to both cyclosporine and tacrolimus. The fifth case had features of thrombotic microangiopathy related to an antiphospholipid syndrome in a patient with systemic lupus erythematosus. CONCLUSIONS: In the literature, the most-frequent cause of hemolytic uremic syndrome in patients following renal transplantation is recurrence of the hemolytic uremic syndrome. Other causes include drug-related (cyclosporine, tacrolimus) toxicity, procoagulant status, and antibody-mediated rejection. We found that the most-frequent cause of thrombotic microangiopathy was drug related, secondary mainly to cyclosporine. In the current study, the frequency of thrombotic microangiopathy was similar to the percentage reported in the literature (20%).","[{'text': 'thrombotic microangiopathy', 'type': 'Disease', 'start': 16, 'end': 42, 'mesh': 'D057049'}, {'text': 'Thrombotic microangiopathy', 'type': 'Disease', 'start': 101, 'end': 127, 'mesh': 'D057049'}, {'text': 'thrombotic microangiopathy', 'type': 'Disease', 'start': 227, 'end': 253, 'mesh': 'D057049'}, {'text': 'hemolytic uremic syndrome', 'type': 'Disease', 'start': 279, 'end': 304, 'mesh': 'D006463'}, {'text': 'thrombotic microangiopathy', 'type': 'Disease', 'start': 342, 'end': 368, 'mesh': 'D057049'}, {'text': 'thrombotic microangiopathy', 'type': 'Disease', 'start': 502, 'end': 528, 'mesh': 'D057049'}, {'text': 'thrombotic microangiopathy', 'type': 'Disease', 'start': 824, 'end': 850, 'mesh': 'D057049'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 1095, 'end': 1107, 'mesh': 'D016572'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 1142, 'end': 1154, 'mesh': 'D016572'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 1159, 'end': 1169, 'mesh': 'D016559'}, {'text': 'thrombotic microangiopathy', 'type': 'Disease', 'start': 1202, 'end': 1228, 'mesh': 'D057049'}, {'text': 'antiphospholipid syndrome', 'type': 'Disease', 'start': 1243, 'end': 1268, 'mesh': 'D016736'}, {'text': 'systemic lupus erythematosus', 'type': 'Disease', 'start': 1287, 'end': 1315, 'mesh': 'D008180'}, {'text': 'hemolytic uremic syndrome', 'type': 'Disease', 'start': 1376, 'end': 1401, 'mesh': 'D006463'}, {'text': 'hemolytic uremic syndrome', 'type': 'Disease', 'start': 1467, 'end': 1492, 'mesh': 'D006463'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 1529, 'end': 1541, 'mesh': 'D016572'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 1543, 'end': 1553, 'mesh': 'D016559'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1555, 'end': 1563, 'mesh': 'D064420'}, {'text': 'thrombotic microangiopathy', 'type': 'Disease', 'start': 1660, 'end': 1686, 'mesh': 'D057049'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 1725, 'end': 1737, 'mesh': 'D016572'}, {'text': 'thrombotic microangiopathy', 'type': 'Disease', 'start': 1778, 'end': 1804, 'mesh': 'D057049'}]"
+437,15188772,Severe reversible left ventricular systolic and diastolic dysfunction due to accidental iatrogenic epinephrine overdose.,"Catecholamine-induced cardiomyopathy due to chronic excess of endogenous catecholamines has been recognized for decades as a clinical phenomenon. In contrast, reports of myocardial dysfunction due to acute iatrogenic overdose are rare. A 35-year-old woman whose cervix uteri was inadvertently injected with 8 mg of epinephrine developed myocardial stunning that was characterized by severe hemodynamic compromise, profound, albeit transient, left ventricular systolic and diastolic dysfunction, and only modestly elevated biochemical markers of myocardial necrosis. Our case illustrates the serious consequences of medical errors that can be avoided through improved medication labeling and staff supervision.","[{'text': 'left ventricular systolic and diastolic dysfunction', 'type': 'Disease', 'start': 18, 'end': 69, 'mesh': 'D018487'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 99, 'end': 110, 'mesh': 'D004837'}, {'text': 'overdose', 'type': 'Disease', 'start': 111, 'end': 119, 'mesh': 'D062787'}, {'text': 'Catecholamine', 'type': 'Chemical', 'start': 121, 'end': 134, 'mesh': 'D002395'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 143, 'end': 157, 'mesh': 'D009202'}, {'text': 'catecholamines', 'type': 'Chemical', 'start': 194, 'end': 208, 'mesh': 'D002395'}, {'text': 'myocardial dysfunction', 'type': 'Disease', 'start': 291, 'end': 313, 'mesh': 'D009202'}, {'text': 'overdose', 'type': 'Disease', 'start': 338, 'end': 346, 'mesh': 'D062787'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 436, 'end': 447, 'mesh': 'D004837'}, {'text': 'myocardial stunning', 'type': 'Disease', 'start': 458, 'end': 477, 'mesh': 'D017682'}, {'text': 'left ventricular systolic and diastolic dysfunction', 'type': 'Disease', 'start': 563, 'end': 614, 'mesh': 'D018487'}, {'text': 'myocardial necrosis', 'type': 'Disease', 'start': 666, 'end': 685, 'mesh': 'D009202'}]"
+438,15130900,Urinary bladder cancer in Wegener's granulomatosis: risks and relation to cyclophosphamide.,"OBJECTIVE: To assess and characterise the risk of bladder cancer, and its relation to cyclophosphamide, in patients with Wegener's granulomatosis. METHODS: In the population based, nationwide Swedish Inpatient Register a cohort of 1065 patients with Wegener's granulomatosis, 1969-95, was identified. Through linkage with the Swedish Cancer Register, all subjects in this cohort diagnosed with bladder cancer were identified. Nested within the cohort, a matched case-control study was performed to estimate the association between cyclophosphamide and bladder cancer using odds ratios (ORs) as relative risk. In the cohort the cumulative risk of bladder cancer after Wegener's granulomatosis, and the relative prevalence of a history of bladder cancer at the time of diagnosis of Wegener's granulomatosis, were also estimated. RESULTS: The median cumulative doses of cyclophosphamide among cases (n = 11) and controls (n = 25) were 113 g and 25 g, respectively. The risk of bladder cancer doubled for every 10 g increment in cyclophosphamide (OR = 2.0, 95% confidence interval (CI) 0.8 to 4.9). Treatment duration longer than 1 year was associated with an eightfold increased risk (OR = 7.7, 95% CI 0.9 to 69). The absolute risk for bladder cancer in the cohort reached 10% 16 years after diagnosis of Wegener's granulomatosis, and a history of bladder cancer was (non-significantly) twice as common as expected at the time of diagnosis of Wegener's granulomatosis. CONCLUSION: The results indicate a dose-response relationship between cyclophosphamide and the risk of bladder cancer, high cumulative risks in the entire cohort, and also the possibility of risk factors operating even before Wegener's granulomatosis.","[{'text': 'Urinary bladder cancer', 'type': 'Disease', 'start': 0, 'end': 22, 'mesh': 'D001749'}, {'text': ""Wegener's granulomatosis"", 'type': 'Disease', 'start': 26, 'end': 50, 'mesh': 'D014890'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 74, 'end': 90, 'mesh': 'D003520'}, {'text': 'bladder cancer', 'type': 'Disease', 'start': 142, 'end': 156, 'mesh': 'D001749'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 178, 'end': 194, 'mesh': 'D003520'}, {'text': ""Wegener's granulomatosis"", 'type': 'Disease', 'start': 213, 'end': 237, 'mesh': 'D014890'}, {'text': ""Wegener's granulomatosis"", 'type': 'Disease', 'start': 342, 'end': 366, 'mesh': 'D014890'}, {'text': 'Cancer', 'type': 'Disease', 'start': 426, 'end': 432, 'mesh': 'D009369'}, {'text': 'bladder cancer', 'type': 'Disease', 'start': 486, 'end': 500, 'mesh': 'D001749'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 623, 'end': 639, 'mesh': 'D003520'}, {'text': 'bladder cancer', 'type': 'Disease', 'start': 644, 'end': 658, 'mesh': 'D001749'}, {'text': 'bladder cancer', 'type': 'Disease', 'start': 738, 'end': 752, 'mesh': 'D001749'}, {'text': ""Wegener's granulomatosis"", 'type': 'Disease', 'start': 759, 'end': 783, 'mesh': 'D014890'}, {'text': 'bladder cancer', 'type': 'Disease', 'start': 829, 'end': 843, 'mesh': 'D001749'}, {'text': ""Wegener's granulomatosis"", 'type': 'Disease', 'start': 872, 'end': 896, 'mesh': 'D014890'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 959, 'end': 975, 'mesh': 'D003520'}, {'text': 'bladder cancer', 'type': 'Disease', 'start': 1066, 'end': 1080, 'mesh': 'D001749'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 1117, 'end': 1133, 'mesh': 'D003520'}, {'text': 'bladder cancer', 'type': 'Disease', 'start': 1325, 'end': 1339, 'mesh': 'D001749'}, {'text': ""Wegener's granulomatosis"", 'type': 'Disease', 'start': 1394, 'end': 1418, 'mesh': 'D014890'}, {'text': 'bladder cancer', 'type': 'Disease', 'start': 1437, 'end': 1451, 'mesh': 'D001749'}, {'text': ""Wegener's granulomatosis"", 'type': 'Disease', 'start': 1532, 'end': 1556, 'mesh': 'D014890'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 1628, 'end': 1644, 'mesh': 'D003520'}, {'text': 'bladder cancer', 'type': 'Disease', 'start': 1661, 'end': 1675, 'mesh': 'D001749'}, {'text': ""Wegener's granulomatosis"", 'type': 'Disease', 'start': 1784, 'end': 1808, 'mesh': 'D014890'}]"
+439,12707296,L-arginine transport in humans with cortisol-induced hypertension.,"A deficient L-arginine-nitric oxide system is implicated in cortisol-induced hypertension. We investigate whether abnormalities in L-arginine uptake contribute to this deficiency. Eight healthy men were recruited. Hydrocortisone acetate (50 mg) was given orally every 6 hours for 24 hours after a 5-day fixed-salt diet (150 mmol/d). Crossover studies were performed 2 weeks apart. Thirty milliliters of blood was obtained for isolation of peripheral blood mononuclear cells after each treatment period. L-arginine uptake was assessed in mononuclear cells incubated with L-arginine (1 to 300 micromol/L), incorporating 100 nmol/L [3H]-l-arginine for a period of 5 minutes at 37 degrees C. Forearm [3H]-L-arginine extraction was calculated after infusion of [3H]-L-arginine into the brachial artery at a rate of 100 nCi/min for 80 minutes. Deep forearm venous samples were collected for determination of L-arginine extraction. Plasma cortisol concentrations were significantly raised during the active phase (323+/-43 to 1082+/-245 mmol/L, P<0.05). Systolic blood pressure was elevated by an average of 7 mm Hg. Neither L-arginine transport into mononuclear cells (placebo vs active, 26.3+/-3.6 vs 29.0+/-2.1 pmol/10 000 cells per 5 minutes, respectively, at an l-arginine concentration of 300 micromol/L) nor L-arginine extraction in the forearm (at 80 minutes, placebo vs active, 1 868 904+/-434 962 vs 2 013 910+/-770 619 disintegrations per minute) was affected by cortisol treatment; ie, that L-arginine uptake is not affected by short-term cortisol treatment. We conclude that cortisol-induced increases in blood pressure are not associated with abnormalities in the l-arginine transport system.","[{'text': 'L-arginine', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D001120'}, {'text': 'cortisol', 'type': 'Chemical', 'start': 36, 'end': 44, 'mesh': 'D006854'}, {'text': 'hypertension', 'type': 'Disease', 'start': 53, 'end': 65, 'mesh': 'D006973'}, {'text': 'L-arginine', 'type': 'Chemical', 'start': 79, 'end': 89, 'mesh': 'D001120'}, {'text': 'nitric oxide', 'type': 'Chemical', 'start': 90, 'end': 102, 'mesh': 'D009569'}, {'text': 'cortisol', 'type': 'Chemical', 'start': 127, 'end': 135, 'mesh': 'D006854'}, {'text': 'hypertension', 'type': 'Disease', 'start': 144, 'end': 156, 'mesh': 'D006973'}, {'text': 'L-arginine', 'type': 'Chemical', 'start': 198, 'end': 208, 'mesh': 'D001120'}, {'text': 'Hydrocortisone acetate', 'type': 'Chemical', 'start': 281, 'end': 303, 'mesh': 'C021650'}, {'text': 'L-arginine', 'type': 'Chemical', 'start': 570, 'end': 580, 'mesh': 'D001120'}, {'text': 'L-arginine', 'type': 'Chemical', 'start': 637, 'end': 647, 'mesh': 'D001120'}, {'text': '[3H]-l-arginine', 'type': 'Chemical', 'start': 696, 'end': 711, 'mesh': 'D001120'}, {'text': '[3H]-L-arginine', 'type': 'Chemical', 'start': 763, 'end': 778, 'mesh': 'D001120'}, {'text': '[3H]-L-arginine', 'type': 'Chemical', 'start': 823, 'end': 838, 'mesh': 'D001120'}, {'text': 'L-arginine', 'type': 'Chemical', 'start': 969, 'end': 979, 'mesh': 'D001120'}, {'text': 'cortisol', 'type': 'Chemical', 'start': 999, 'end': 1007, 'mesh': 'D006854'}, {'text': 'L-arginine', 'type': 'Chemical', 'start': 1185, 'end': 1195, 'mesh': 'D001120'}, {'text': 'l-arginine', 'type': 'Chemical', 'start': 1327, 'end': 1337, 'mesh': 'D001120'}, {'text': 'L-arginine', 'type': 'Chemical', 'start': 1375, 'end': 1385, 'mesh': 'D001120'}, {'text': 'cortisol', 'type': 'Chemical', 'start': 1534, 'end': 1542, 'mesh': 'D006854'}, {'text': 'L-arginine', 'type': 'Chemical', 'start': 1563, 'end': 1573, 'mesh': 'D001120'}, {'text': 'cortisol', 'type': 'Chemical', 'start': 1611, 'end': 1619, 'mesh': 'D006854'}, {'text': 'cortisol', 'type': 'Chemical', 'start': 1648, 'end': 1656, 'mesh': 'D006854'}, {'text': 'increases in blood pressure', 'type': 'Disease', 'start': 1665, 'end': 1692, 'mesh': 'D006973'}, {'text': 'l-arginine', 'type': 'Chemical', 'start': 1738, 'end': 1748, 'mesh': 'D001120'}]"
+440,12695819,MR imaging with quantitative diffusion mapping of tacrolimus-induced neurotoxicity in organ transplant patients.,"Our objective was to investigate brain MR imaging findings and the utility of diffusion-weighted (DW) imaging in organ transplant patients who developed neurologic symptoms during tacrolimus therapy. Brain MR studies, including DW imaging, were prospectively performed in 14 organ transplant patients receiving tacrolimus who developed neurologic complications. In each patient who had abnormalities on the initial MR study, a follow-up MR study was performed 1 month later. Apparent diffusion coefficient (ADC) values on the initial MR study were correlated with reversibility of the lesions. Of the 14 patients, 5 (35.7%) had white matter abnormalities, 1 (7.1%) had putaminal hemorrhage, and 8 (57.1%) had normal findings on initial MR images. Among the 5 patients with white matter abnormalities, 4 patients (80.0%) showed higher than normal ADC values on initial MR images, and all showed complete resolution on follow-up images. The remaining 1 patient (20.0%) showed lower than normal ADC value and showed incomplete resolution with cortical laminar necrosis. Diffusion-weighted imaging may be useful in predicting the outcomes of the lesions of tacrolimus-induced neurotoxicity.","[{'text': 'tacrolimus', 'type': 'Chemical', 'start': 50, 'end': 60, 'mesh': 'D016559'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 69, 'end': 82, 'mesh': 'D020258'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 293, 'end': 303, 'mesh': 'D016559'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 424, 'end': 434, 'mesh': 'D016559'}, {'text': 'neurologic complications', 'type': 'Disease', 'start': 449, 'end': 473, 'mesh': 'D009422'}, {'text': 'white matter abnormalities', 'type': 'Disease', 'start': 741, 'end': 767, 'mesh': 'D056784'}, {'text': 'putaminal hemorrhage', 'type': 'Disease', 'start': 782, 'end': 802, 'mesh': 'D020146'}, {'text': 'white matter abnormalities', 'type': 'Disease', 'start': 886, 'end': 912, 'mesh': 'D056784'}, {'text': 'cortical laminar necrosis', 'type': 'Disease', 'start': 1153, 'end': 1178, 'mesh': 'D001927'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 1266, 'end': 1276, 'mesh': 'D016559'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 1285, 'end': 1298, 'mesh': 'D020258'}]"
+441,12596116,Octreotide-induced hypoxemia and pulmonary hypertension in premature neonates.,"The authors report 2 cases of premature neonates who had enterocutaneous fistula complicating necrotizing enterocolitis. Pulmonary hypertension developed after administration of a somatostatin analogue, octreotide, to enhance resolution of the fistula. The authors discuss the mechanism of the occurrence of this complication and recommend caution of its use in high-risk premature neonates.","[{'text': 'Octreotide', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D015282'}, {'text': 'hypoxemia', 'type': 'Disease', 'start': 19, 'end': 28, 'mesh': 'D000860'}, {'text': 'pulmonary hypertension', 'type': 'Disease', 'start': 33, 'end': 55, 'mesh': 'D006976'}, {'text': 'fistula', 'type': 'Disease', 'start': 152, 'end': 159, 'mesh': 'D005402'}, {'text': 'necrotizing enterocolitis', 'type': 'Disease', 'start': 173, 'end': 198, 'mesh': 'D020345'}, {'text': 'Pulmonary hypertension', 'type': 'Disease', 'start': 200, 'end': 222, 'mesh': 'D006976'}, {'text': 'octreotide', 'type': 'Chemical', 'start': 282, 'end': 292, 'mesh': 'D015282'}, {'text': 'fistula', 'type': 'Disease', 'start': 323, 'end': 330, 'mesh': 'D005402'}]"
+442,11875660,Sequential observations of exencephaly and subsequent morphological changes by mouse exo utero development system: analysis of the mechanism of transformation from exencephaly to anencephaly.,"Anencephaly has been suggested to develop from exencephaly; however, there is little direct experimental evidence to support this, and the mechanism of transformation remains unclear. We examined this theory using the exo utero development system that allows direct and sequential observations of mid- to late-gestation mouse embryos. We observed the exencephaly induced by 5-azacytidine at embryonic day 13.5 (E13.5), let the embryos develop exo utero until E18.5, and re-observed the same embryos at E18.5. We confirmed several cases of transformation from exencephaly to anencephaly. However, in many cases, the exencephalic brain tissue was preserved with more or less reduction during this period. To analyze the transformation patterns, we classified the exencephaly by size and shape of the exencephalic tissue into several types at E13.5 and E18.5. It was found that the transformation of exencephalic tissue was not simply size-dependent, and all cases of anencephaly at E18.5 resulted from embryos with a large amount of exencephalic tissue at E13.5. Microscopic observation showed the configuration of exencephaly at E13.5, frequent hemorrhaging and detachment of the neural plate from surface ectoderm in the exencephalic head at E15.5, and multiple modes of reduction in the exencephalic tissue at E18.5. From observations of the vasculature, altered distribution patterns of vessels were identified in the exencephalic head. These findings suggest that overgrowth of the exencephalic neural tissue causes the altered distribution patterns of vessels, subsequent peripheral circulatory failure and/or hemorrhaging in various parts of the exencephalic head, leading to the multiple modes of tissue reduction during transformation from exencephaly to anencephaly.","[{'text': 'exencephaly', 'type': 'Disease', 'start': 27, 'end': 38, 'mesh': 'D009436'}, {'text': 'exencephaly', 'type': 'Disease', 'start': 164, 'end': 175, 'mesh': 'D009436'}, {'text': 'anencephaly', 'type': 'Disease', 'start': 179, 'end': 190, 'mesh': 'D000757'}, {'text': 'Anencephaly', 'type': 'Disease', 'start': 192, 'end': 203, 'mesh': 'D000757'}, {'text': 'exencephaly', 'type': 'Disease', 'start': 239, 'end': 250, 'mesh': 'D009436'}, {'text': 'exencephaly', 'type': 'Disease', 'start': 543, 'end': 554, 'mesh': 'D009436'}, {'text': '5-azacytidine', 'type': 'Chemical', 'start': 566, 'end': 579, 'mesh': 'D001374'}, {'text': 'exencephaly', 'type': 'Disease', 'start': 751, 'end': 762, 'mesh': 'D009436'}, {'text': 'anencephaly', 'type': 'Disease', 'start': 766, 'end': 777, 'mesh': 'D000757'}, {'text': 'exencephalic', 'type': 'Disease', 'start': 807, 'end': 819, 'mesh': 'D009436'}, {'text': 'exencephaly', 'type': 'Disease', 'start': 953, 'end': 964, 'mesh': 'D009436'}, {'text': 'exencephalic', 'type': 'Disease', 'start': 990, 'end': 1002, 'mesh': 'D009436'}, {'text': 'exencephalic', 'type': 'Disease', 'start': 1089, 'end': 1101, 'mesh': 'D009436'}, {'text': 'anencephaly', 'type': 'Disease', 'start': 1157, 'end': 1168, 'mesh': 'D000757'}, {'text': 'exencephalic', 'type': 'Disease', 'start': 1223, 'end': 1235, 'mesh': 'D009436'}, {'text': 'exencephaly', 'type': 'Disease', 'start': 1305, 'end': 1316, 'mesh': 'D009436'}, {'text': 'hemorrhaging', 'type': 'Disease', 'start': 1336, 'end': 1348, 'mesh': 'D006470'}, {'text': 'exencephalic', 'type': 'Disease', 'start': 1413, 'end': 1425, 'mesh': 'D009436'}, {'text': 'exencephalic', 'type': 'Disease', 'start': 1480, 'end': 1492, 'mesh': 'D009436'}, {'text': 'exencephalic', 'type': 'Disease', 'start': 1612, 'end': 1624, 'mesh': 'D009436'}, {'text': 'exencephalic', 'type': 'Disease', 'start': 1677, 'end': 1689, 'mesh': 'D009436'}, {'text': 'circulatory failure', 'type': 'Disease', 'start': 1779, 'end': 1798, 'mesh': 'D012769'}, {'text': 'hemorrhaging', 'type': 'Disease', 'start': 1806, 'end': 1818, 'mesh': 'D006470'}, {'text': 'exencephalic', 'type': 'Disease', 'start': 1843, 'end': 1855, 'mesh': 'D009436'}, {'text': 'exencephaly', 'type': 'Disease', 'start': 1939, 'end': 1950, 'mesh': 'D009436'}, {'text': 'anencephaly', 'type': 'Disease', 'start': 1954, 'end': 1965, 'mesh': 'D000757'}]"
+443,11166519,Acute cocaine-induced seizures: differential sensitivity of six inbred mouse strains.,"Mature male and female mice from six inbred stains were tested for susceptibility to behavioral seizures induced by a single injection of cocaine. Cocaine was injected ip over a range of doses (50-100 mg/kg) and behavior was monitored for 20 minutes. Seizure end points included latency to forelimb or hindlimb clonus, latency to clonic running seizure and latency to jumping bouncing seizure. A range of strain specific sensitivities was documented with A/J and SJL mice being most sensitive and C57BL/6J most resistant. DBA/2J, BALB/cByJ and NZW/LacJ strains exhibited intermediate sensitivity. EEG recordings were made in SJL, A/J and C57BL/6J mice revealing a close correspondence between electrical activity and behavior. Additionally, levels of cocaine determined in hippocampus and cortex were not different between sensitive and resistant strains. Additional studies of these murine strains may be useful for investigating genetic influences on cocaine-induced seizures.","[{'text': 'cocaine', 'type': 'Chemical', 'start': 6, 'end': 13, 'mesh': 'D003042'}, {'text': 'seizures', 'type': 'Disease', 'start': 22, 'end': 30, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 182, 'end': 190, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 224, 'end': 231, 'mesh': 'D003042'}, {'text': 'Cocaine', 'type': 'Chemical', 'start': 233, 'end': 240, 'mesh': 'D003042'}, {'text': 'Seizure', 'type': 'Disease', 'start': 337, 'end': 344, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 431, 'end': 438, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 471, 'end': 478, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 837, 'end': 844, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1039, 'end': 1046, 'mesh': 'D003042'}, {'text': 'seizures', 'type': 'Disease', 'start': 1055, 'end': 1063, 'mesh': 'D012640'}]"
+444,8701950,Microangiopathic hemolytic anemia complicating FK506 (tacrolimus) therapy.,"We describe 3 episodes of microangiopathic hemolytic anemia (MAHA) in 2 solid organ recipients under FK506 (tacrolimus) therapy. In both cases, discontinuation of FK506 and treatment with plasma exchange, fresh frozen plasma replacement, corticosteroids, aspirin, and dipyridamole led to resolution of MAHA. In one patient, reintroduction of FK506 led to rapid recurrence of MAHA. FK506-associated MAHA is probably rare but physicians must be aware of this severe complication. In our experience and according to the literature, FK506 does not seem to cross-react with cyclosporin A (CyA), an immuno-suppressive drug already known to induce MAHA.","[{'text': 'Microangiopathic hemolytic anemia', 'type': 'Disease', 'start': 0, 'end': 33, 'mesh': 'D000743'}, {'text': 'FK506', 'type': 'Chemical', 'start': 47, 'end': 52, 'mesh': 'D016559'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 54, 'end': 64, 'mesh': 'D016559'}, {'text': 'microangiopathic hemolytic anemia', 'type': 'Disease', 'start': 101, 'end': 134, 'mesh': 'D000743'}, {'text': 'MAHA', 'type': 'Disease', 'start': 136, 'end': 140, 'mesh': 'D000743'}, {'text': 'FK506', 'type': 'Chemical', 'start': 176, 'end': 181, 'mesh': 'D016559'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 183, 'end': 193, 'mesh': 'D016559'}, {'text': 'FK506', 'type': 'Chemical', 'start': 238, 'end': 243, 'mesh': 'D016559'}, {'text': 'corticosteroids', 'type': 'Chemical', 'start': 313, 'end': 328, 'mesh': 'D000305'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 330, 'end': 337, 'mesh': 'D001241'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 343, 'end': 355, 'mesh': 'D004176'}, {'text': 'MAHA', 'type': 'Disease', 'start': 377, 'end': 381, 'mesh': 'D000743'}, {'text': 'FK506', 'type': 'Chemical', 'start': 417, 'end': 422, 'mesh': 'D016559'}, {'text': 'MAHA', 'type': 'Disease', 'start': 450, 'end': 454, 'mesh': 'D000743'}, {'text': 'FK506', 'type': 'Chemical', 'start': 456, 'end': 461, 'mesh': 'D016559'}, {'text': 'MAHA', 'type': 'Disease', 'start': 473, 'end': 477, 'mesh': 'D000743'}, {'text': 'FK506', 'type': 'Chemical', 'start': 604, 'end': 609, 'mesh': 'D016559'}, {'text': 'cyclosporin A', 'type': 'Chemical', 'start': 644, 'end': 657, 'mesh': 'D016572'}, {'text': 'CyA', 'type': 'Chemical', 'start': 659, 'end': 662, 'mesh': 'D016572'}, {'text': 'MAHA', 'type': 'Disease', 'start': 716, 'end': 720, 'mesh': 'D000743'}]"
+445,7292072,Variant ventricular tachycardia in desipramine toxicity.,"We report a case of variant ventricular tachycardia induced by desipramine toxicity. Unusual features of the arrhythmia are repetitive group beating, progressive shortening of the R-R interval, progressive widening of the QRS complex with eventual failure of intraventricular conduction, and changes in direction of the QRS axis. Recognition of variant ventricular tachycardia is important because therapy differs from that of classic ventricular tachycardia.","[{'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 8, 'end': 31, 'mesh': 'D017180'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 35, 'end': 46, 'mesh': 'D003891'}, {'text': 'toxicity', 'type': 'Disease', 'start': 47, 'end': 55, 'mesh': 'D064420'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 85, 'end': 108, 'mesh': 'D017180'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 120, 'end': 131, 'mesh': 'D003891'}, {'text': 'toxicity', 'type': 'Disease', 'start': 132, 'end': 140, 'mesh': 'D064420'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 166, 'end': 176, 'mesh': 'D001145'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 410, 'end': 433, 'mesh': 'D017180'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 492, 'end': 515, 'mesh': 'D017180'}]"
+446,4027862,"Desipramine-induced delirium at ""subtherapeutic"" concentrations: a case report.","An elderly patient treated with low dose Desipramine developed a delirium while her plasma level was in the ""subtherapeutic"" range. Delirium, which may be induced by tricyclic drug therapy in the elderly, can be caused by tricyclics with low anticholinergic potency. Therapeutic ranges for antidepressants that have been derived from general adult population studies may not be appropriate for the elderly. Further studies of specifically elderly patients are now required to establish safer and more appropriate guidelines for drug therapy.","[{'text': 'Desipramine', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D003891'}, {'text': 'delirium', 'type': 'Disease', 'start': 20, 'end': 28, 'mesh': 'D003693'}, {'text': 'Desipramine', 'type': 'Chemical', 'start': 121, 'end': 132, 'mesh': 'D003891'}, {'text': 'delirium', 'type': 'Disease', 'start': 145, 'end': 153, 'mesh': 'D003693'}, {'text': 'Delirium', 'type': 'Disease', 'start': 212, 'end': 220, 'mesh': 'D003693'}, {'text': 'antidepressants', 'type': 'Chemical', 'start': 370, 'end': 385, 'mesh': 'D000928'}]"
+447,2484011,Mouse strain-dependent effect of amantadine on motility and brain biogenic amines.,"The effect of amantadine hydrochloride, injected i.p. in 6 increments of 100 mg/kg each over 30 hr, on mouse motility and whole brain content of selected biogenic amines and major metabolites was studied in 4 strains of mice. These were the albino Sprague-Dawley ICR and BALB/C, the black C57BL/6 and the brown CDF-I mouse strains. Amantadine treatment produced a biphasic effect on mouse motility. The initial dose of amantadine depressed locomotor activity in all mouse strains studied with the BALB/C mice being the most sensitive. Subsequent amantadine treatments produced enhancement of motility from corresponding control in all mouse strains with the BALB/C mice being the least sensitive. The locomotor activity was decreased from corresponding controls in all strains studied, except for the ICR mice, during an overnight drug-free period following the fourth amantadine treatment. Readministration of amantadine, after a drug-free overnight period, increased motility from respective saline control in all strains with exception of the BALB/C mice where suppression of motility occurred. Treatment with amantadine did not alter whole brain dopamine levels but decreased the amounts of 3,4-dihydroxyphenylacetic acid in the BALB/C mice compared to saline control. Conversely, brain normetanephrine concentration was increased from saline control by amantadine in the BALB/C mice. The results suggest a strain-dependent effect of amantadine on motility and indicate a differential response to the acute and multiple dose regimens used. The BALB/C mouse was the most sensitive strain and could serve as the strain of choice for evaluating the side effects of amantadine. The biochemical results of brain biogenic amines of BALB/C mouse strain suggest a probable decrease of catecholamine turnover rate and/or metabolism by monoamine oxidase and a resulting increase in O-methylation of norepinephrine which may account for a behavioral depression caused by amantadine in the BALB/C mice.","[{'text': 'amantadine', 'type': 'Chemical', 'start': 33, 'end': 43, 'mesh': 'D000547'}, {'text': 'amines', 'type': 'Chemical', 'start': 75, 'end': 81, 'mesh': 'D000588'}, {'text': 'amantadine hydrochloride', 'type': 'Chemical', 'start': 97, 'end': 121, 'mesh': 'D000547'}, {'text': 'amines', 'type': 'Chemical', 'start': 246, 'end': 252, 'mesh': 'D000588'}, {'text': 'Amantadine', 'type': 'Chemical', 'start': 415, 'end': 425, 'mesh': 'D000547'}, {'text': 'amantadine', 'type': 'Chemical', 'start': 502, 'end': 512, 'mesh': 'D000547'}, {'text': 'depressed', 'type': 'Disease', 'start': 513, 'end': 522, 'mesh': 'D003866'}, {'text': 'amantadine', 'type': 'Chemical', 'start': 629, 'end': 639, 'mesh': 'D000547'}, {'text': 'amantadine', 'type': 'Chemical', 'start': 952, 'end': 962, 'mesh': 'D000547'}, {'text': 'amantadine', 'type': 'Chemical', 'start': 994, 'end': 1004, 'mesh': 'D000547'}, {'text': 'suppression of motility', 'type': 'Disease', 'start': 1147, 'end': 1170, 'mesh': 'D011596'}, {'text': 'amantadine', 'type': 'Chemical', 'start': 1196, 'end': 1206, 'mesh': 'D000547'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1233, 'end': 1241, 'mesh': 'D004298'}, {'text': '3,4-dihydroxyphenylacetic acid', 'type': 'Chemical', 'start': 1278, 'end': 1308, 'mesh': 'D015102'}, {'text': 'normetanephrine', 'type': 'Chemical', 'start': 1374, 'end': 1389, 'mesh': 'D009647'}, {'text': 'amantadine', 'type': 'Chemical', 'start': 1441, 'end': 1451, 'mesh': 'D000547'}, {'text': 'amantadine', 'type': 'Chemical', 'start': 1521, 'end': 1531, 'mesh': 'D000547'}, {'text': 'amantadine', 'type': 'Chemical', 'start': 1749, 'end': 1759, 'mesh': 'D000547'}, {'text': 'amines', 'type': 'Chemical', 'start': 1803, 'end': 1809, 'mesh': 'D000588'}, {'text': 'catecholamine', 'type': 'Chemical', 'start': 1864, 'end': 1877, 'mesh': 'D002395'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 1976, 'end': 1990, 'mesh': 'D009638'}, {'text': 'behavioral depression', 'type': 'Disease', 'start': 2015, 'end': 2036, 'mesh': 'D011596'}, {'text': 'amantadine', 'type': 'Chemical', 'start': 2047, 'end': 2057, 'mesh': 'D000547'}]"
+448,2396046,No enhancement by phenobarbital of the hepatocarcinogenicity of a choline-devoid diet in the rat.,"An experiment was performed to test whether inclusion of phenobarbital in a choline-devoid diet would increase the hepatocarcinogenicity of the diet. Groups of 5-week old male Fischer-344 rats were fed for 7-25 months semipurified choline-devoid or choline-supplemented diets, containing or not 0.06% phenobarbital. No hepatic preneoplastic nodules or hepatocellular carcinomas developed in rats fed the plain choline-supplemented diet, while one preneoplastic nodule and one hepatocellular carcinoma developed in two rats fed the same diet containing phenobarbital. The incidence of preneoplastic nodules and of hepatocellular carcinomas was 10% and 37%, respectively, in rats fed the plain choline-devoid diet, and 17% and 30%, in rats fed the phenobarbital-containing choline-devoid diet. The results evinced no enhancement of the hepatocarcinogenicity of the choline-devoid diet by phenobarbital. Sporadic neoplastic lesions were observed in organs other than the liver of some of the animals, irrespective of the diet fed.","[{'text': 'phenobarbital', 'type': 'Chemical', 'start': 18, 'end': 31, 'mesh': 'D010634'}, {'text': 'choline', 'type': 'Chemical', 'start': 66, 'end': 73, 'mesh': 'D002794'}, {'text': 'phenobarbital', 'type': 'Chemical', 'start': 155, 'end': 168, 'mesh': 'D010634'}, {'text': 'choline', 'type': 'Chemical', 'start': 174, 'end': 181, 'mesh': 'D002794'}, {'text': 'choline', 'type': 'Chemical', 'start': 329, 'end': 336, 'mesh': 'D002794'}, {'text': 'choline', 'type': 'Chemical', 'start': 347, 'end': 354, 'mesh': 'D002794'}, {'text': 'phenobarbital', 'type': 'Chemical', 'start': 399, 'end': 412, 'mesh': 'D010634'}, {'text': 'hepatocellular carcinomas', 'type': 'Disease', 'start': 450, 'end': 475, 'mesh': 'D006528'}, {'text': 'choline', 'type': 'Chemical', 'start': 508, 'end': 515, 'mesh': 'D002794'}, {'text': 'hepatocellular carcinoma', 'type': 'Disease', 'start': 574, 'end': 598, 'mesh': 'D006528'}, {'text': 'phenobarbital', 'type': 'Chemical', 'start': 650, 'end': 663, 'mesh': 'D010634'}, {'text': 'hepatocellular carcinomas', 'type': 'Disease', 'start': 711, 'end': 736, 'mesh': 'D006528'}, {'text': 'choline', 'type': 'Chemical', 'start': 790, 'end': 797, 'mesh': 'D002794'}, {'text': 'phenobarbital', 'type': 'Chemical', 'start': 844, 'end': 857, 'mesh': 'D010634'}, {'text': 'choline', 'type': 'Chemical', 'start': 869, 'end': 876, 'mesh': 'D002794'}, {'text': 'choline', 'type': 'Chemical', 'start': 961, 'end': 968, 'mesh': 'D002794'}, {'text': 'phenobarbital', 'type': 'Chemical', 'start': 984, 'end': 997, 'mesh': 'D010634'}]"
+449,2008831,Effect of direct intracoronary administration of methylergonovine in patients with and without variant angina.,"The effects of intracoronary administration of methylergonovine were studied in 21 patients with variant angina and 22 patients with atypical chest pain and in others without angina pectoris (control group). Methylergonovine was administered continuously at a rate of 10 micrograms/min up to 50 micrograms. In all patients with variant angina, coronary spasm was provoked at a mean dose of 28 +/- 13 micrograms (mean +/- SD). In the control group neither ischemic ST change nor localized spasm occurred. The basal tone of the right coronary artery was significantly lower than that of the left coronary artery. The percentage of vasoconstriction of the right coronary artery was significantly higher than that of the left coronary artery. These results suggest that spasm provocation tests, which use an intracoronary injection of a relatively low dose of methylergonovine, have a high sensitivity in variant angina and the vasoreactivity of the right coronary artery may be greater than that of the other coronary arteries.","[{'text': 'methylergonovine', 'type': 'Chemical', 'start': 49, 'end': 65, 'mesh': 'D008755'}, {'text': 'variant angina', 'type': 'Disease', 'start': 95, 'end': 109, 'mesh': 'D000788'}, {'text': 'methylergonovine', 'type': 'Chemical', 'start': 158, 'end': 174, 'mesh': 'D008755'}, {'text': 'variant angina', 'type': 'Disease', 'start': 208, 'end': 222, 'mesh': 'D000788'}, {'text': 'chest pain', 'type': 'Disease', 'start': 253, 'end': 263, 'mesh': 'D002637'}, {'text': 'angina pectoris', 'type': 'Disease', 'start': 286, 'end': 301, 'mesh': 'D000787'}, {'text': 'Methylergonovine', 'type': 'Chemical', 'start': 319, 'end': 335, 'mesh': 'D008755'}, {'text': 'variant angina', 'type': 'Disease', 'start': 439, 'end': 453, 'mesh': 'D000788'}, {'text': 'coronary spasm', 'type': 'Disease', 'start': 455, 'end': 469, 'mesh': 'D003329'}, {'text': 'spasm', 'type': 'Disease', 'start': 599, 'end': 604, 'mesh': 'D013035'}, {'text': 'spasm', 'type': 'Disease', 'start': 877, 'end': 882, 'mesh': 'D013035'}, {'text': 'methylergonovine', 'type': 'Chemical', 'start': 967, 'end': 983, 'mesh': 'D008755'}, {'text': 'variant angina', 'type': 'Disease', 'start': 1012, 'end': 1026, 'mesh': 'D000788'}]"
+450,1732369,Dobutamine stress echocardiography: a sensitive indicator of diminished myocardial function in asymptomatic doxorubicin-treated long-term survivors of childhood cancer.,"Doxorubicin is an effective anticancer chemotherapeutic agent known to cause acute and chronic cardiomyopathy. To develop a more sensitive echocardiographic screening test for cardiac damage due to doxorubicin, a cohort study was performed using dobutamine infusion to differentiate asymptomatic long-term survivors of childhood cancer treated with doxorubicin from healthy control subjects. Echocardiographic data from the experimental group of 21 patients (mean age 16 +/- 5 years) treated from 1.6 to 14.3 years (median 5.3) before this study with 27 to 532 mg/m2 of doxorubicin (mean 196) were compared with echocardiographic data from 12 normal age-matched control subjects. Graded dobutamine infusions of 0.5, 2.5, 5 and 10 micrograms/kg per min were administered. Echocardiographic Doppler studies were performed before infusion and after 15 min of infusion at each rate. Dobutamine infusion at 10 micrograms/kg per min was discontinued after six studies secondary to a 50% incidence rate of adverse symptoms. The most important findings were that compared with values in control subjects, end-systolic left ventricular posterior wall dimension and percent of left ventricular posterior wall thickening in doxorubicin-treated patients were decreased at baseline study and these findings were more clearly delineated with dobutamine stimulation. End-systolic left ventricular posterior wall dimension at baseline for the doxorubicin-treated group was 11 +/- 1.9 mm versus 13.1 +/- 1.5 mm for control subjects (p less than 0.01). End-systolic left ventricular posterior wall dimension at the 5-micrograms/kg per min dobutamine infusion for the doxorubicin-treated group was 14.1 +/- 2.4 mm versus 19.3 +/- 2.6 mm for control subjects (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)","[{'text': 'Dobutamine', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D004280'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 108, 'end': 119, 'mesh': 'D004317'}, {'text': 'cancer', 'type': 'Disease', 'start': 161, 'end': 167, 'mesh': 'D009369'}, {'text': 'Doxorubicin', 'type': 'Chemical', 'start': 169, 'end': 180, 'mesh': 'D004317'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 264, 'end': 278, 'mesh': 'D009202'}, {'text': 'cardiac damage', 'type': 'Disease', 'start': 345, 'end': 359, 'mesh': 'D006331'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 367, 'end': 378, 'mesh': 'D004317'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 415, 'end': 425, 'mesh': 'D004280'}, {'text': 'cancer', 'type': 'Disease', 'start': 498, 'end': 504, 'mesh': 'D009369'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 518, 'end': 529, 'mesh': 'D004317'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 739, 'end': 750, 'mesh': 'D004317'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 856, 'end': 866, 'mesh': 'D004280'}, {'text': 'Dobutamine', 'type': 'Chemical', 'start': 1048, 'end': 1058, 'mesh': 'D004280'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1382, 'end': 1393, 'mesh': 'D004317'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 1497, 'end': 1507, 'mesh': 'D004280'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1596, 'end': 1607, 'mesh': 'D004317'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 1790, 'end': 1800, 'mesh': 'D004280'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1818, 'end': 1829, 'mesh': 'D004317'}]"
+451,234669,Effects of aminophylline on the threshold for initiating ventricular fibrillation during respiratory failure.,"Cardiac arrhythmias have frequently been reported in association with respiratory failure. The possible additive role of pharmacologic agents in precipitating cardiac disturbances in patients with respiratory failure has only recently been emphasized. The effects of aminophylline on the ventricular fibrillation threshold during normal acid-base conditions and during respiratory failure were studied in anesthetized open chest dogs. The ventricular fibrillation threshold was measured by passing a gated train of 12 constant current pulses through the ventricular myocardium during the vulnerable period of the cardiac cycle. During the infusion of aminophylline, the ventricular fibrillation threshold was reduced by 30 to 40 percent of the control when pH and partial pressures of oxygen (PO2) and carbon dioxide (CO2) were kept within normal limits. When respiratory failure was produced by hypoventilation (pH 7.05 to 7.25; PC02 70 to 100 mm Hg: P02 20 to 40 mm Hg), infusion of aminophylline resulted in an even greater decrease in ventricular fibrillation threshold to 60 percent of the control level. These experiments suggest that although many factors may contribute to the increased incidence of ventricular arrhythmias in respiratory failure, pharmacologic agents, particularly aminophylline, may play a significant role.","[{'text': 'aminophylline', 'type': 'Chemical', 'start': 11, 'end': 24, 'mesh': 'D000628'}, {'text': 'ventricular fibrillation', 'type': 'Disease', 'start': 57, 'end': 81, 'mesh': 'D014693'}, {'text': 'respiratory failure', 'type': 'Disease', 'start': 89, 'end': 108, 'mesh': 'D012131'}, {'text': 'Cardiac arrhythmias', 'type': 'Disease', 'start': 110, 'end': 129, 'mesh': 'D001145'}, {'text': 'respiratory failure', 'type': 'Disease', 'start': 180, 'end': 199, 'mesh': 'D012131'}, {'text': 'cardiac disturbances', 'type': 'Disease', 'start': 269, 'end': 289, 'mesh': 'D006331'}, {'text': 'respiratory failure', 'type': 'Disease', 'start': 307, 'end': 326, 'mesh': 'D012131'}, {'text': 'aminophylline', 'type': 'Chemical', 'start': 377, 'end': 390, 'mesh': 'D000628'}, {'text': 'ventricular fibrillation', 'type': 'Disease', 'start': 398, 'end': 422, 'mesh': 'D014693'}, {'text': 'respiratory failure', 'type': 'Disease', 'start': 479, 'end': 498, 'mesh': 'D012131'}, {'text': 'ventricular fibrillation', 'type': 'Disease', 'start': 549, 'end': 573, 'mesh': 'D014693'}, {'text': 'aminophylline', 'type': 'Chemical', 'start': 761, 'end': 774, 'mesh': 'D000628'}, {'text': 'ventricular fibrillation', 'type': 'Disease', 'start': 780, 'end': 804, 'mesh': 'D014693'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 895, 'end': 901, 'mesh': 'D010100'}, {'text': 'PO2', 'type': 'Chemical', 'start': 903, 'end': 906, 'mesh': 'C093415'}, {'text': 'carbon dioxide', 'type': 'Chemical', 'start': 912, 'end': 926, 'mesh': 'D002245'}, {'text': 'CO2', 'type': 'Chemical', 'start': 928, 'end': 931, 'mesh': 'D002245'}, {'text': 'respiratory failure', 'type': 'Disease', 'start': 970, 'end': 989, 'mesh': 'D012131'}, {'text': 'hypoventilation', 'type': 'Disease', 'start': 1006, 'end': 1021, 'mesh': 'D007040'}, {'text': 'aminophylline', 'type': 'Chemical', 'start': 1095, 'end': 1108, 'mesh': 'D000628'}, {'text': 'ventricular fibrillation', 'type': 'Disease', 'start': 1149, 'end': 1173, 'mesh': 'D014693'}, {'text': 'ventricular arrhythmias', 'type': 'Disease', 'start': 1318, 'end': 1341, 'mesh': 'D001145'}, {'text': 'respiratory failure', 'type': 'Disease', 'start': 1345, 'end': 1364, 'mesh': 'D012131'}, {'text': 'aminophylline', 'type': 'Chemical', 'start': 1401, 'end': 1414, 'mesh': 'D000628'}]"
+452,16740173,Case report: acute unintentional carbachol intoxication.,"INTRODUCTION: Intoxications with carbachol, a muscarinic cholinergic receptor agonist are rare. We report an interesting case investigating a (near) fatal poisoning. METHODS: The son of an 84-year-old male discovered a newspaper report stating clinical success with plant extracts in Alzheimer's disease. The mode of action was said to be comparable to that of the synthetic compound 'carbamylcholin'; that is, carbachol. He bought 25 g of carbachol as pure substance in a pharmacy, and the father was administered 400 to 500 mg. Carbachol concentrations in serum and urine on day 1 and 2 of hospital admission were analysed by HPLC-mass spectrometry. RESULTS: Minutes after oral administration, the patient developed nausea, sweating and hypotension, and finally collapsed. Bradycardia, cholinergic symptoms and asystole occurred. Initial cardiopulmonary resuscitation and immediate treatment with adrenaline (epinephrine), atropine and furosemide was successful. On hospital admission, blood pressure of the intubated, bradyarrhythmic patient was 100/65 mmHg. Further signs were hyperhidrosis, hypersalivation, bronchorrhoea, and severe miosis; the electrocardiographic finding was atrio-ventricular dissociation. High doses of atropine (up to 50 mg per 24 hours), adrenaline and dopamine were necessary. The patient was extubated 1 week later. However, increased dyspnoea and bronchospasm necessitated reintubation. Respiratory insufficiency was further worsened by Proteus mirabilis infection and severe bronchoconstriction. One week later, the patient was again extubated and 3 days later was transferred to a peripheral ward. On the next day he died, probably as a result of heart failure. Serum samples from the first and second days contained 3.6 and 1.9 mg/l carbachol, respectively. The corresponding urine concentrations amounted to 374 and 554 mg/l. CONCLUSION: This case started with a media report in a popular newspaper, initiated by published, peer-reviewed research on herbals, and involved human failure in a case history, medical examination and clinical treatment. For the first time, an analytical method for the determination of carbachol in plasma and urine has been developed. The analysed carbachol concentration exceeded the supposed serum level resulting from a therapeutic dose by a factor of 130 to 260. Especially in old patients, intensivists should consider intoxications (with cholinergics) as a cause of acute cardiovascular failure.","[{'text': 'carbachol', 'type': 'Chemical', 'start': 33, 'end': 42, 'mesh': 'D002217'}, {'text': 'carbachol', 'type': 'Chemical', 'start': 90, 'end': 99, 'mesh': 'D002217'}, {'text': 'poisoning', 'type': 'Disease', 'start': 212, 'end': 221, 'mesh': 'D011041'}, {'text': ""Alzheimer's disease"", 'type': 'Disease', 'start': 341, 'end': 360, 'mesh': 'D000544'}, {'text': 'carbamylcholin', 'type': 'Chemical', 'start': 442, 'end': 456, 'mesh': 'D002217'}, {'text': 'carbachol', 'type': 'Chemical', 'start': 468, 'end': 477, 'mesh': 'D002217'}, {'text': 'carbachol', 'type': 'Chemical', 'start': 497, 'end': 506, 'mesh': 'D002217'}, {'text': 'Carbachol', 'type': 'Chemical', 'start': 587, 'end': 596, 'mesh': 'D002217'}, {'text': 'nausea', 'type': 'Disease', 'start': 775, 'end': 781, 'mesh': 'D009325'}, {'text': 'hypotension', 'type': 'Disease', 'start': 796, 'end': 807, 'mesh': 'D007022'}, {'text': 'Bradycardia', 'type': 'Disease', 'start': 832, 'end': 843, 'mesh': 'D001919'}, {'text': 'asystole', 'type': 'Disease', 'start': 870, 'end': 878, 'mesh': 'D006323'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 956, 'end': 966, 'mesh': 'D004837'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 968, 'end': 979, 'mesh': 'D004837'}, {'text': 'atropine', 'type': 'Chemical', 'start': 982, 'end': 990, 'mesh': 'D001285'}, {'text': 'furosemide', 'type': 'Chemical', 'start': 995, 'end': 1005, 'mesh': 'D005665'}, {'text': 'hyperhidrosis', 'type': 'Disease', 'start': 1138, 'end': 1151, 'mesh': 'D006945'}, {'text': 'hypersalivation', 'type': 'Disease', 'start': 1153, 'end': 1168, 'mesh': 'D012798'}, {'text': 'bronchorrhoea', 'type': 'Disease', 'start': 1170, 'end': 1183, 'mesh': '-1'}, {'text': 'miosis', 'type': 'Disease', 'start': 1196, 'end': 1202, 'mesh': 'D015877'}, {'text': 'atrio-ventricular dissociation', 'type': 'Disease', 'start': 1241, 'end': 1271, 'mesh': 'D006327'}, {'text': 'atropine', 'type': 'Chemical', 'start': 1287, 'end': 1295, 'mesh': 'D001285'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 1324, 'end': 1334, 'mesh': 'D004837'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1339, 'end': 1347, 'mesh': 'D004298'}, {'text': 'dyspnoea', 'type': 'Disease', 'start': 1423, 'end': 1431, 'mesh': 'D004417'}, {'text': 'bronchospasm', 'type': 'Disease', 'start': 1436, 'end': 1448, 'mesh': 'D001986'}, {'text': 'Respiratory insufficiency', 'type': 'Disease', 'start': 1476, 'end': 1501, 'mesh': 'D012131'}, {'text': 'Proteus mirabilis infection', 'type': 'Disease', 'start': 1526, 'end': 1553, 'mesh': 'D011512'}, {'text': 'heart failure', 'type': 'Disease', 'start': 1738, 'end': 1751, 'mesh': 'D006333'}, {'text': 'carbachol', 'type': 'Chemical', 'start': 1825, 'end': 1834, 'mesh': 'D002217'}, {'text': 'carbachol', 'type': 'Chemical', 'start': 2208, 'end': 2217, 'mesh': 'D002217'}, {'text': 'carbachol', 'type': 'Chemical', 'start': 2271, 'end': 2280, 'mesh': 'D002217'}, {'text': 'acute cardiovascular failure', 'type': 'Disease', 'start': 2495, 'end': 2523, 'mesh': 'D002318'}]"
+453,12464714,Crossover comparison of efficacy and preference for rizatriptan 10 mg versus ergotamine/caffeine in migraine.,"Rizatriptan is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized double- blind crossover outpatient study assessed the preference for 1 rizatriptan 10 mg tablet to 2 ergotamine 1 mg/caffeine 100 mg tablets in 439 patients treating a single migraine attack with each therapy. Of patients expressing a preference (89.1%), more than twice as many preferred rizatriptan to ergotamine/caffeine (69.9 vs. 30.1%, p < or = 0.001). Faster relief of headache was the most important reason for preference, cited by 67.3% of patients preferring rizatriptan and 54.2% of patients who preferred ergotamine/caffeine. The co-primary endpoint of being pain free at 2 h was also in favor of rizatriptan. Forty-nine percent of patients were pain free 2 h after rizatriptan, compared with 24.3% treated with ergotamine/caffeine (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Headache relief at 2 h was 75.9% for rizatriptan and 47.3% for ergotamine/caffeine (p < or = 0.001), with rizatriptan being superior to ergotamine/caffeine within 30 min of dosing. Almost 36% of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication within 24 h, compared to 20% of patients on ergotamine/caffeine (p < or = 0.001). Rizatriptan was also superior to ergotamine/caffeine in the proportions of patients with no nausea, vomiting, phonophobia or photophobia and for patients with normal function 2 h after drug intake (p < or = 0.001). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (69.8%) than at 2 h after treatment with ergotamine/caffeine (38.6%, p < or = 0.001). Recurrence rates were 31.4% with rizatriptan and 15.3% with ergotamine/caffeine. Both active treatments were well tolerated. The most common adverse events (incidence > or = 5% in one group) after rizatriptan and ergotamine/caffeine, respectively, were dizziness (6.7 and 5.3%), nausea (4.2 and 8.5%) and somnolence (5.5 and 2.3%).","[{'text': 'rizatriptan', 'type': 'Chemical', 'start': 52, 'end': 63, 'mesh': 'C093622'}, {'text': 'ergotamine', 'type': 'Chemical', 'start': 77, 'end': 87, 'mesh': 'D004878'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 88, 'end': 96, 'mesh': 'D002110'}, {'text': 'migraine', 'type': 'Disease', 'start': 100, 'end': 108, 'mesh': 'D008881'}, {'text': 'Rizatriptan', 'type': 'Chemical', 'start': 110, 'end': 121, 'mesh': 'C093622'}, {'text': '5-HT', 'type': 'Chemical', 'start': 137, 'end': 141, 'mesh': 'D012701'}, {'text': 'migraine', 'type': 'Disease', 'start': 245, 'end': 253, 'mesh': 'D008881'}, {'text': 'rizatriptan', 'type': 'Chemical', 'start': 342, 'end': 353, 'mesh': 'C093622'}, {'text': 'ergotamine', 'type': 'Chemical', 'start': 372, 'end': 382, 'mesh': 'D004878'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 388, 'end': 396, 'mesh': 'D002110'}, {'text': 'migraine', 'type': 'Disease', 'start': 446, 'end': 454, 'mesh': 'D008881'}, {'text': 'rizatriptan', 'type': 'Chemical', 'start': 560, 'end': 571, 'mesh': 'C093622'}, {'text': 'ergotamine', 'type': 'Chemical', 'start': 575, 'end': 585, 'mesh': 'D004878'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 586, 'end': 594, 'mesh': 'D002110'}, {'text': 'headache', 'type': 'Disease', 'start': 646, 'end': 654, 'mesh': 'D006261'}, {'text': 'rizatriptan', 'type': 'Chemical', 'start': 739, 'end': 750, 'mesh': 'C093622'}, {'text': 'ergotamine', 'type': 'Chemical', 'start': 787, 'end': 797, 'mesh': 'D004878'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 798, 'end': 806, 'mesh': 'D002110'}, {'text': 'pain', 'type': 'Disease', 'start': 841, 'end': 845, 'mesh': 'D010146'}, {'text': 'rizatriptan', 'type': 'Chemical', 'start': 879, 'end': 890, 'mesh': 'C093622'}, {'text': 'pain', 'type': 'Disease', 'start': 928, 'end': 932, 'mesh': 'D010146'}, {'text': 'rizatriptan', 'type': 'Chemical', 'start': 948, 'end': 959, 'mesh': 'C093622'}, {'text': 'ergotamine', 'type': 'Chemical', 'start': 994, 'end': 1004, 'mesh': 'D004878'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1005, 'end': 1013, 'mesh': 'D002110'}, {'text': 'rizatriptan', 'type': 'Chemical', 'start': 1032, 'end': 1043, 'mesh': 'C093622'}, {'text': 'Headache', 'type': 'Disease', 'start': 1084, 'end': 1092, 'mesh': 'D006261'}, {'text': 'rizatriptan', 'type': 'Chemical', 'start': 1121, 'end': 1132, 'mesh': 'C093622'}, {'text': 'ergotamine', 'type': 'Chemical', 'start': 1147, 'end': 1157, 'mesh': 'D004878'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1158, 'end': 1166, 'mesh': 'D002110'}, {'text': 'rizatriptan', 'type': 'Chemical', 'start': 1190, 'end': 1201, 'mesh': 'C093622'}, {'text': 'ergotamine', 'type': 'Chemical', 'start': 1220, 'end': 1230, 'mesh': 'D004878'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1231, 'end': 1239, 'mesh': 'D002110'}, {'text': 'rizatriptan', 'type': 'Chemical', 'start': 1295, 'end': 1306, 'mesh': 'C093622'}, {'text': 'pain', 'type': 'Disease', 'start': 1312, 'end': 1316, 'mesh': 'D010146'}, {'text': 'ergotamine', 'type': 'Chemical', 'start': 1429, 'end': 1439, 'mesh': 'D004878'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1440, 'end': 1448, 'mesh': 'D002110'}, {'text': 'Rizatriptan', 'type': 'Chemical', 'start': 1467, 'end': 1478, 'mesh': 'C093622'}, {'text': 'ergotamine', 'type': 'Chemical', 'start': 1500, 'end': 1510, 'mesh': 'D004878'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1511, 'end': 1519, 'mesh': 'D002110'}, {'text': 'nausea', 'type': 'Disease', 'start': 1559, 'end': 1565, 'mesh': 'D009325'}, {'text': 'vomiting', 'type': 'Disease', 'start': 1567, 'end': 1575, 'mesh': 'D014839'}, {'text': 'phonophobia', 'type': 'Disease', 'start': 1577, 'end': 1588, 'mesh': 'D012001'}, {'text': 'photophobia', 'type': 'Disease', 'start': 1592, 'end': 1603, 'mesh': 'D020795'}, {'text': 'rizatriptan', 'type': 'Chemical', 'start': 1767, 'end': 1778, 'mesh': 'C093622'}, {'text': 'ergotamine', 'type': 'Chemical', 'start': 1820, 'end': 1830, 'mesh': 'D004878'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1831, 'end': 1839, 'mesh': 'D002110'}, {'text': 'rizatriptan', 'type': 'Chemical', 'start': 1898, 'end': 1909, 'mesh': 'C093622'}, {'text': 'ergotamine', 'type': 'Chemical', 'start': 1925, 'end': 1935, 'mesh': 'D004878'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1936, 'end': 1944, 'mesh': 'D002110'}, {'text': 'rizatriptan', 'type': 'Chemical', 'start': 2062, 'end': 2073, 'mesh': 'C093622'}, {'text': 'ergotamine', 'type': 'Chemical', 'start': 2078, 'end': 2088, 'mesh': 'D004878'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 2089, 'end': 2097, 'mesh': 'D002110'}, {'text': 'dizziness', 'type': 'Disease', 'start': 2118, 'end': 2127, 'mesh': 'D004244'}, {'text': 'nausea', 'type': 'Disease', 'start': 2144, 'end': 2150, 'mesh': 'D009325'}, {'text': 'somnolence', 'type': 'Disease', 'start': 2170, 'end': 2180, 'mesh': 'D006970'}]"
+454,6203452,Thrombotic microangiopathy and renal failure associated with antineoplastic chemotherapy.,"Five patients with carcinoma developed thrombotic microangiopathy (characterized by renal insufficiency, microangiopathic hemolytic anemia, and usually thrombocytopenia) after treatment with cisplatin, bleomycin, and a vinca alkaloid. One patient had thrombotic thrombocytopenic purpura, three the hemolytic-uremic syndrome, and one an apparent forme fruste of one of these disorders. Histologic examination of the renal tissue showed evidence of intravascular coagulation, primarily affecting the small arteries, arterioles, and glomeruli. Because each patient was tumor-free or had only a small tumor at the onset of this syndrome, the thrombotic microangiopathy may have been induced by chemotherapy. Diagnosis of this potentially fatal complication may be delayed or missed if renal tissue or the peripheral blood smear is not examined, because renal failure may be ascribed to cisplatin nephrotoxicity and the anemia and thrombocytopenia to drug-induced bone marrow suppression.","[{'text': 'Thrombotic microangiopathy', 'type': 'Disease', 'start': 0, 'end': 26, 'mesh': 'D057049'}, {'text': 'renal failure', 'type': 'Disease', 'start': 31, 'end': 44, 'mesh': 'D051437'}, {'text': 'carcinoma', 'type': 'Disease', 'start': 109, 'end': 118, 'mesh': 'D002277'}, {'text': 'thrombotic microangiopathy', 'type': 'Disease', 'start': 129, 'end': 155, 'mesh': 'D057049'}, {'text': 'renal insufficiency', 'type': 'Disease', 'start': 174, 'end': 193, 'mesh': 'D051437'}, {'text': 'microangiopathic hemolytic anemia', 'type': 'Disease', 'start': 195, 'end': 228, 'mesh': 'D000743'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 242, 'end': 258, 'mesh': 'D013921'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 281, 'end': 290, 'mesh': 'D002945'}, {'text': 'bleomycin', 'type': 'Chemical', 'start': 292, 'end': 301, 'mesh': 'D001761'}, {'text': 'vinca alkaloid', 'type': 'Chemical', 'start': 309, 'end': 323, 'mesh': 'D014748'}, {'text': 'thrombotic thrombocytopenic purpura', 'type': 'Disease', 'start': 341, 'end': 376, 'mesh': 'D011697'}, {'text': 'hemolytic-uremic syndrome', 'type': 'Disease', 'start': 388, 'end': 413, 'mesh': 'D006463'}, {'text': 'intravascular coagulation', 'type': 'Disease', 'start': 537, 'end': 562, 'mesh': 'D004211'}, {'text': 'tumor', 'type': 'Disease', 'start': 656, 'end': 661, 'mesh': 'D009369'}, {'text': 'tumor', 'type': 'Disease', 'start': 687, 'end': 692, 'mesh': 'D009369'}, {'text': 'thrombotic microangiopathy', 'type': 'Disease', 'start': 728, 'end': 754, 'mesh': 'D057049'}, {'text': 'renal failure', 'type': 'Disease', 'start': 939, 'end': 952, 'mesh': 'D051437'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 972, 'end': 981, 'mesh': 'D002945'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 982, 'end': 996, 'mesh': 'D007674'}, {'text': 'anemia', 'type': 'Disease', 'start': 1005, 'end': 1011, 'mesh': 'D000740'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 1016, 'end': 1032, 'mesh': 'D013921'}, {'text': 'bone marrow suppression', 'type': 'Disease', 'start': 1049, 'end': 1072, 'mesh': 'D001855'}]"
+455,20528871,"Salvage therapy with nelarabine, etoposide, and cyclophosphamide in relapsed/refractory paediatric T-cell lymphoblastic leukaemia and lymphoma.","A combination of 5 d of nelarabine (AraG) with 5 d of etoposide (VP) and cyclophosphamide (CPM) and prophylactic intrathecal chemotherapy was used as salvage therapy in seven children with refractory or relapsed T-cell leukaemia or lymphoma. The most common side effects attributable to the AraG included Grade 2 and 3 sensory and motor neuropathy and musculoskeletal pain. Haematological toxicity was greater for the combination than AraG alone, although median time to neutrophil and platelet recovery was consistent with other salvage therapies. All patients had some response to the combined therapy and five of the seven went into complete remission after one or two courses of AraG/VP/CPM. Our experience supports the safety of giving AraG as salvage therapy in synchrony with etoposide and cyclophosphamide, although neurological toxicity must be closely monitored.","[{'text': 'nelarabine', 'type': 'Chemical', 'start': 21, 'end': 31, 'mesh': 'C104457'}, {'text': 'etoposide', 'type': 'Chemical', 'start': 33, 'end': 42, 'mesh': 'D005047'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 48, 'end': 64, 'mesh': 'D003520'}, {'text': 'nelarabine', 'type': 'Chemical', 'start': 168, 'end': 178, 'mesh': 'C104457'}, {'text': 'AraG', 'type': 'Chemical', 'start': 180, 'end': 184, 'mesh': 'C104457'}, {'text': 'etoposide', 'type': 'Chemical', 'start': 198, 'end': 207, 'mesh': 'D005047'}, {'text': 'VP', 'type': 'Chemical', 'start': 209, 'end': 211, 'mesh': 'D005047'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 217, 'end': 233, 'mesh': 'D003520'}, {'text': 'CPM', 'type': 'Chemical', 'start': 235, 'end': 238, 'mesh': 'D003520'}, {'text': 'AraG', 'type': 'Chemical', 'start': 435, 'end': 439, 'mesh': 'C104457'}, {'text': 'neuropathy', 'type': 'Disease', 'start': 481, 'end': 491, 'mesh': 'D009422'}, {'text': 'musculoskeletal pain', 'type': 'Disease', 'start': 496, 'end': 516, 'mesh': 'D059352'}, {'text': 'Haematological toxicity', 'type': 'Disease', 'start': 518, 'end': 541, 'mesh': 'D006402'}, {'text': 'AraG', 'type': 'Chemical', 'start': 579, 'end': 583, 'mesh': 'C104457'}, {'text': 'AraG', 'type': 'Chemical', 'start': 827, 'end': 831, 'mesh': 'C104457'}, {'text': 'VP', 'type': 'Chemical', 'start': 832, 'end': 834, 'mesh': 'D005047'}, {'text': 'CPM', 'type': 'Chemical', 'start': 835, 'end': 838, 'mesh': 'D003520'}, {'text': 'AraG', 'type': 'Chemical', 'start': 885, 'end': 889, 'mesh': 'C104457'}, {'text': 'etoposide', 'type': 'Chemical', 'start': 927, 'end': 936, 'mesh': 'D005047'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 941, 'end': 957, 'mesh': 'D003520'}, {'text': 'neurological toxicity', 'type': 'Disease', 'start': 968, 'end': 989, 'mesh': 'D009422'}]"
+456,11672959,The 3-week sulphasalazine syndrome strikes again.,"A 34-year-old lady developed a constellation of dermatitis, fever, lymphadenopathy and hepatitis, beginning on the 17th day of a course of oral sulphasalazine for sero-negative rheumatoid arthritis. Cervical and inguinal lymph node biopsies showed the features of severe necrotising lymphadenitis, associated with erythrophagocytosis and prominent eosinophilic infiltrates, without viral inclusion bodies, suggestive of an adverse drug reaction.A week later, fulminant drug-induced hepatitis, associated with the presence of anti-nuclear autoantibodies (but not with other markers of autoimmunity), and accompanied by multi-organ failure and sepsis, supervened. She subsequently died some 5 weeks after the commencement of her drug therapy.Post-mortem examination showed evidence of massive hepatocellular necrosis, acute hypersensitivity myocarditis, focal acute tubulo-interstitial nephritis and extensive bone marrow necrosis, with no evidence of malignancy. It is thought that the clinico-pathological features and chronology of this case bore the hallmarks of the so-called ""3-week sulphasalazine syndrome"", a rare, but often fatal, immunoallergic reaction to sulphasalazine.","[{'text': 'sulphasalazine', 'type': 'Chemical', 'start': 11, 'end': 25, 'mesh': 'D012460'}, {'text': 'dermatitis', 'type': 'Disease', 'start': 98, 'end': 108, 'mesh': 'D003872'}, {'text': 'fever', 'type': 'Disease', 'start': 110, 'end': 115, 'mesh': 'D005334'}, {'text': 'lymphadenopathy', 'type': 'Disease', 'start': 117, 'end': 132, 'mesh': 'D008206'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 137, 'end': 146, 'mesh': 'D056486'}, {'text': 'sulphasalazine', 'type': 'Chemical', 'start': 194, 'end': 208, 'mesh': 'D012460'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 227, 'end': 247, 'mesh': 'D001172'}, {'text': 'lymphadenitis', 'type': 'Disease', 'start': 333, 'end': 346, 'mesh': 'D008199'}, {'text': 'adverse drug reaction', 'type': 'Disease', 'start': 473, 'end': 494, 'mesh': 'D064420'}, {'text': 'drug-induced hepatitis', 'type': 'Disease', 'start': 519, 'end': 541, 'mesh': 'D056486'}, {'text': 'autoimmunity', 'type': 'Disease', 'start': 634, 'end': 646, 'mesh': 'D001327'}, {'text': 'multi-organ failure', 'type': 'Disease', 'start': 668, 'end': 687, 'mesh': 'D009102'}, {'text': 'sepsis', 'type': 'Disease', 'start': 692, 'end': 698, 'mesh': 'D018805'}, {'text': 'massive hepatocellular necrosis', 'type': 'Disease', 'start': 833, 'end': 864, 'mesh': 'D047508'}, {'text': 'myocarditis', 'type': 'Disease', 'start': 889, 'end': 900, 'mesh': 'D009205'}, {'text': 'nephritis', 'type': 'Disease', 'start': 934, 'end': 943, 'mesh': 'D009393'}, {'text': 'bone marrow necrosis', 'type': 'Disease', 'start': 958, 'end': 978, 'mesh': 'D001855'}, {'text': 'malignancy', 'type': 'Disease', 'start': 1000, 'end': 1010, 'mesh': 'D009369'}, {'text': 'sulphasalazine', 'type': 'Chemical', 'start': 1137, 'end': 1151, 'mesh': 'D012460'}, {'text': 'sulphasalazine', 'type': 'Chemical', 'start': 1215, 'end': 1229, 'mesh': 'D012460'}]"
+457,11928786,Bupropion (Zyban) toxicity.,"Bupropion is a monocyclic antidepressant structurally related to amphetamine. Zyban, a sustained-release formulation of bupropion hydrochloride, was recently released in Ireland, as a smoking cessation aid. In the initial 6 months since it's introduction, 12 overdose cases have been reported to The National Poisons Information Centre. 8 patients developed symptoms of toxicity. Common features included tachycardia, drowsiness, hallucinations and convulsions. Two patients developed severe cardiac arrhythmias, including one patient who was resuscitated following a cardiac arrest. All patients recovered without sequelae. We report a case of a 31 year old female who required admission to the Intensive Care Unit for ventilation and full supportive therapy, following ingestion of 13.5g bupropion. Recurrent seizures were treated with diazepam and broad complex tachycardia was successfully treated with adenosine. Zyban caused significant neurological and cardiovascular toxicity in overdose. The potential toxic effects should be considered when prescribing it as a smoking cessation aid.","[{'text': 'Bupropion', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D016642'}, {'text': 'Zyban', 'type': 'Chemical', 'start': 11, 'end': 16, 'mesh': 'D016642'}, {'text': 'toxicity', 'type': 'Disease', 'start': 18, 'end': 26, 'mesh': 'D064420'}, {'text': 'Bupropion', 'type': 'Chemical', 'start': 28, 'end': 37, 'mesh': 'D016642'}, {'text': 'antidepressant', 'type': 'Chemical', 'start': 54, 'end': 68, 'mesh': 'D000928'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 93, 'end': 104, 'mesh': 'D000661'}, {'text': 'Zyban', 'type': 'Chemical', 'start': 106, 'end': 111, 'mesh': 'D016642'}, {'text': 'bupropion hydrochloride', 'type': 'Chemical', 'start': 148, 'end': 171, 'mesh': 'D016642'}, {'text': 'overdose', 'type': 'Disease', 'start': 287, 'end': 295, 'mesh': 'D062787'}, {'text': 'toxicity', 'type': 'Disease', 'start': 398, 'end': 406, 'mesh': 'D064420'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 433, 'end': 444, 'mesh': 'D013610'}, {'text': 'hallucinations', 'type': 'Disease', 'start': 458, 'end': 472, 'mesh': 'D006212'}, {'text': 'convulsions', 'type': 'Disease', 'start': 477, 'end': 488, 'mesh': 'D012640'}, {'text': 'cardiac arrhythmias', 'type': 'Disease', 'start': 520, 'end': 539, 'mesh': 'D001145'}, {'text': 'cardiac arrest', 'type': 'Disease', 'start': 596, 'end': 610, 'mesh': 'D006323'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 818, 'end': 827, 'mesh': 'D016642'}, {'text': 'seizures', 'type': 'Disease', 'start': 839, 'end': 847, 'mesh': 'D012640'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 866, 'end': 874, 'mesh': 'D003975'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 893, 'end': 904, 'mesh': 'D013610'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 935, 'end': 944, 'mesh': 'D000241'}, {'text': 'Zyban', 'type': 'Chemical', 'start': 946, 'end': 951, 'mesh': 'D016642'}, {'text': 'overdose', 'type': 'Disease', 'start': 1015, 'end': 1023, 'mesh': 'D062787'}]"
+458,7977601,Survey of complications of indocyanine green angiography in Japan.,"PURPOSE: We evaluated the safety of indocyanine green for use in fundus angiography. METHODS: We sent a questionnaire concerning complications of indocyanine green to 32 institutions in Japan, which were selected on the basis of the client list from the Topcon Company, which manufactures the indocyanine green fundus camera. RESULTS: Ophthalmologists at 15 institutions responded, reporting a total of 3,774 indocyanine green angiograms performed on 2,820 patients between June 1984 and September 1992. Before angiography, intradermal or intravenous indocyanine green testing, or both was performed at 13 of 15 institutions. For three patients, the decision was made not to proceed with angiography after positive preangiographic testing. The dosage of indocyanine green used for angiography varied from 25 to 75 mg, depending upon the institution. There were 13 cases of adverse reactions (0.34%), ten of which were mild reactions such as nausea, exanthema, urtication, itchiness, and urgency to defecate, and did not require treatment. Also recorded were one case of pain of the vein, which required treatment, and two cases of hypotension. The two hypotensive patients required treatment for shock. CONCLUSIONS: A comparison of frequency of adverse reactions to indocyanine green with the previously reported frequency of such reactions to fluorescein sodium indicated that indocyanine green is a safe as fluorescein for use in angiography.","[{'text': 'indocyanine green', 'type': 'Chemical', 'start': 27, 'end': 44, 'mesh': 'D007208'}, {'text': 'indocyanine green', 'type': 'Chemical', 'start': 103, 'end': 120, 'mesh': 'D007208'}, {'text': 'indocyanine green', 'type': 'Chemical', 'start': 213, 'end': 230, 'mesh': 'D007208'}, {'text': 'indocyanine green', 'type': 'Chemical', 'start': 360, 'end': 377, 'mesh': 'D007208'}, {'text': 'indocyanine green', 'type': 'Chemical', 'start': 476, 'end': 493, 'mesh': 'D007208'}, {'text': 'indocyanine green', 'type': 'Chemical', 'start': 618, 'end': 635, 'mesh': 'D007208'}, {'text': 'indocyanine green', 'type': 'Chemical', 'start': 821, 'end': 838, 'mesh': 'D007208'}, {'text': 'nausea', 'type': 'Disease', 'start': 1008, 'end': 1014, 'mesh': 'D009325'}, {'text': 'exanthema', 'type': 'Disease', 'start': 1016, 'end': 1025, 'mesh': 'D005076'}, {'text': 'urtication', 'type': 'Disease', 'start': 1027, 'end': 1037, 'mesh': 'D014581'}, {'text': 'itchiness', 'type': 'Disease', 'start': 1039, 'end': 1048, 'mesh': 'D011537'}, {'text': 'pain', 'type': 'Disease', 'start': 1137, 'end': 1141, 'mesh': 'D010146'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1198, 'end': 1209, 'mesh': 'D007022'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 1219, 'end': 1230, 'mesh': 'D007022'}, {'text': 'shock', 'type': 'Disease', 'start': 1263, 'end': 1268, 'mesh': 'D012769'}, {'text': 'indocyanine green', 'type': 'Chemical', 'start': 1333, 'end': 1350, 'mesh': 'D007208'}, {'text': 'fluorescein sodium', 'type': 'Chemical', 'start': 1411, 'end': 1429, 'mesh': 'D019793'}, {'text': 'indocyanine green', 'type': 'Chemical', 'start': 1445, 'end': 1462, 'mesh': 'D007208'}, {'text': 'fluorescein', 'type': 'Chemical', 'start': 1476, 'end': 1487, 'mesh': 'D019793'}]"
+459,19300402,Bradykinin receptors antagonists and nitric oxide synthase inhibitors in vincristine and streptozotocin induced hyperalgesia in chemotherapy and diabetic neuropathy rat model.,"PURPOSE: The influence of an irreversible inhibitor of constitutive NO synthase (L-NOArg; 1.0 mg/kg ip), a relatively selective inhibitor of inducible NO synthase (L-NIL; 1.0 mg/kg ip) and a relatively specific inhibitor of neuronal NO synthase (7-NI; 0.1 mg/kg ip), on antihyperalgesic action of selective antagonists of B2 and B1 receptors: D-Arg-[Hyp3,Thi5,D-Tic7,Oic8] bradykinin (HOE 140; 70 nmol/kg ip) or des Arg10 HOE 140 (70 nmol/kg ip) respectively, in model of diabetic (streptozotocin-induced) and toxic (vincristine-induced) neuropathy was investigated. METHODS: The changes in pain thresholds were determined using mechanical stimuli--the modification of the classic paw withdrawal test described by Randall-Selitto. RESULTS: The results of this paper confirm that inhibition of bradykinin receptors and inducible NO synthase but not neuronal NO synthase activity reduces diabetic hyperalgesia. Pretreatment with L-NOArg and L-NIL but not 7-NI, significantly increases antihyperalgesic activity both HOE 140 and des Arg10 HOE 140. It was also shown that both products of inducible NO synthase and neuronal NO synthase activation as well as bradykinin are involved in hyperalgesia produced by vincristine. Moreover, L-NOArg and 7-NI but not L-NIL intensify antihyperalgesic activity of HOE 140 or des-Arg10HOE 140 in toxic neuropathy. CONCLUSIONS: Results of these studies suggest that B1 and B2 receptors are engaged in transmission of nociceptive stimuli in both diabetic and toxic neuropathy. In streptozotocin-induced hyperalgesia, inducible NO synthase participates in pronociceptive activity of bradykinin, whereas in vincristine-induced hyperalgesia bradykinin seemed to activate neuronal NO synthase pathway. Therefore, concomitant administration of small doses of bradykinin receptor antagonists and NO synthase inhibitors can be effective in alleviation of neuropathic pain, even in hospital care.","[{'text': 'Bradykinin', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D001920'}, {'text': 'nitric oxide', 'type': 'Chemical', 'start': 37, 'end': 49, 'mesh': 'D009569'}, {'text': 'vincristine', 'type': 'Chemical', 'start': 73, 'end': 84, 'mesh': 'D014750'}, {'text': 'streptozotocin', 'type': 'Chemical', 'start': 89, 'end': 103, 'mesh': 'D013311'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 112, 'end': 124, 'mesh': 'D006930'}, {'text': 'diabetic neuropathy', 'type': 'Disease', 'start': 145, 'end': 164, 'mesh': 'D003929'}, {'text': 'NO', 'type': 'Chemical', 'start': 244, 'end': 246, 'mesh': 'D009569'}, {'text': 'NO', 'type': 'Chemical', 'start': 327, 'end': 329, 'mesh': 'D009569'}, {'text': 'NO', 'type': 'Chemical', 'start': 409, 'end': 411, 'mesh': 'D009569'}, {'text': 'bradykinin', 'type': 'Chemical', 'start': 549, 'end': 559, 'mesh': 'D001920'}, {'text': 'HOE 140', 'type': 'Chemical', 'start': 561, 'end': 568, 'mesh': 'C065679'}, {'text': 'des Arg10 HOE 140', 'type': 'Chemical', 'start': 588, 'end': 605, 'mesh': 'C078665'}, {'text': 'pain', 'type': 'Disease', 'start': 767, 'end': 771, 'mesh': 'D010146'}, {'text': 'bradykinin', 'type': 'Chemical', 'start': 969, 'end': 979, 'mesh': 'D001920'}, {'text': 'NO', 'type': 'Chemical', 'start': 1004, 'end': 1006, 'mesh': 'D009569'}, {'text': 'NO', 'type': 'Chemical', 'start': 1033, 'end': 1035, 'mesh': 'D009569'}, {'text': 'diabetic hyperalgesia', 'type': 'Disease', 'start': 1062, 'end': 1083, 'mesh': 'D006930'}, {'text': 'HOE 140', 'type': 'Chemical', 'start': 1190, 'end': 1197, 'mesh': 'C065679'}, {'text': 'des Arg10 HOE 140', 'type': 'Chemical', 'start': 1202, 'end': 1219, 'mesh': 'C078665'}, {'text': 'NO', 'type': 'Chemical', 'start': 1271, 'end': 1273, 'mesh': 'D009569'}, {'text': 'NO', 'type': 'Chemical', 'start': 1296, 'end': 1298, 'mesh': 'D009569'}, {'text': 'bradykinin', 'type': 'Chemical', 'start': 1330, 'end': 1340, 'mesh': 'D001920'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 1357, 'end': 1369, 'mesh': 'D006930'}, {'text': 'vincristine', 'type': 'Chemical', 'start': 1382, 'end': 1393, 'mesh': 'D014750'}, {'text': 'HOE 140', 'type': 'Chemical', 'start': 1475, 'end': 1482, 'mesh': 'C065679'}, {'text': 'des-Arg10HOE 140', 'type': 'Chemical', 'start': 1486, 'end': 1502, 'mesh': 'C078665'}, {'text': 'toxic neuropathy', 'type': 'Disease', 'start': 1506, 'end': 1522, 'mesh': 'D010523'}, {'text': 'streptozotocin', 'type': 'Chemical', 'start': 1688, 'end': 1702, 'mesh': 'D013311'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 1711, 'end': 1723, 'mesh': 'D006930'}, {'text': 'NO', 'type': 'Chemical', 'start': 1735, 'end': 1737, 'mesh': 'D009569'}, {'text': 'bradykinin', 'type': 'Chemical', 'start': 1790, 'end': 1800, 'mesh': 'D001920'}, {'text': 'vincristine', 'type': 'Chemical', 'start': 1813, 'end': 1824, 'mesh': 'D014750'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 1833, 'end': 1845, 'mesh': 'D006930'}, {'text': 'bradykinin', 'type': 'Chemical', 'start': 1846, 'end': 1856, 'mesh': 'D001920'}, {'text': 'NO', 'type': 'Chemical', 'start': 1885, 'end': 1887, 'mesh': 'D009569'}, {'text': 'bradykinin', 'type': 'Chemical', 'start': 1962, 'end': 1972, 'mesh': 'D001920'}, {'text': 'NO', 'type': 'Chemical', 'start': 1998, 'end': 2000, 'mesh': 'D009569'}, {'text': 'neuropathic pain', 'type': 'Disease', 'start': 2056, 'end': 2072, 'mesh': 'D009437'}]"
+460,15325671,Cardiac toxicity observed in association with high-dose cyclophosphamide-based chemotherapy for metastatic breast cancer.,"INTRODUCTION: Cyclophosphamide is an alkylating agent given frequently as a component of many conditioning regimens. In high doses, its nonhematological dose-limiting toxicity is cardiomyopathy. STUDY DESIGN: We combined paclitaxel, melphalan and high-dose cyclophosphamide, thiotepa, and carboplatin in a triple sequential high-dose regimen for patients with metastatic breast cancer. Analysis was performed on 61 women with chemotherapy-responsive metastatic breast cancer receiving 96-h infusional cyclophosphamide as part of a triple sequential high-dose regimen to assess association between presence of peritransplant congestive heart failure (CHF) and the following pretreatment characteristics: presence of electrocardiogram (EKG) abnormalities, age, hypertension, prior cardiac history, smoking, diabetes mellitus, prior use of anthracyclines, and left-sided chest irradiation. RESULTS: Six of 61 women (10%) developed clinically reversible grade 3 CHF following infusional cyclophosphamide with a median percent decline in ejection fraction of 31%. Incidence of transient cyclophosphamide-related cardiac toxicity (10%) is comparable to previous recorded literature. Older age was significantly correlated with the CHF development; with median ages for the entire group and for patients developing CHF of 45 and 59, respectively. No association was found with other pretreatment characteristics. CONCLUSIONS: As a result of these findings, oncologists should carefully monitor fluid balance in older patients. Routine EKG monitoring during infusional cyclophosphamide did not predict CHF development.","[{'text': 'Cardiac toxicity', 'type': 'Disease', 'start': 0, 'end': 16, 'mesh': 'D066126'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 56, 'end': 72, 'mesh': 'D003520'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 107, 'end': 120, 'mesh': 'D001943'}, {'text': 'Cyclophosphamide', 'type': 'Chemical', 'start': 136, 'end': 152, 'mesh': 'D003520'}, {'text': 'toxicity', 'type': 'Disease', 'start': 289, 'end': 297, 'mesh': 'D064420'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 301, 'end': 315, 'mesh': 'D009202'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 343, 'end': 353, 'mesh': 'D017239'}, {'text': 'melphalan', 'type': 'Chemical', 'start': 355, 'end': 364, 'mesh': 'D008558'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 379, 'end': 395, 'mesh': 'D003520'}, {'text': 'thiotepa', 'type': 'Chemical', 'start': 397, 'end': 405, 'mesh': 'D013852'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 411, 'end': 422, 'mesh': 'D016190'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 493, 'end': 506, 'mesh': 'D001943'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 583, 'end': 596, 'mesh': 'D001943'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 623, 'end': 639, 'mesh': 'D003520'}, {'text': 'congestive heart failure', 'type': 'Disease', 'start': 746, 'end': 770, 'mesh': 'D006333'}, {'text': 'CHF', 'type': 'Disease', 'start': 772, 'end': 775, 'mesh': 'D006333'}, {'text': 'hypertension', 'type': 'Disease', 'start': 881, 'end': 893, 'mesh': 'D006973'}, {'text': 'diabetes mellitus', 'type': 'Disease', 'start': 927, 'end': 944, 'mesh': 'D003920'}, {'text': 'anthracyclines', 'type': 'Chemical', 'start': 959, 'end': 973, 'mesh': 'D018943'}, {'text': 'CHF', 'type': 'Disease', 'start': 1080, 'end': 1083, 'mesh': 'D006333'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 1105, 'end': 1121, 'mesh': 'D003520'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 1204, 'end': 1220, 'mesh': 'D003520'}, {'text': 'cardiac toxicity', 'type': 'Disease', 'start': 1229, 'end': 1245, 'mesh': 'D066126'}, {'text': 'CHF', 'type': 'Disease', 'start': 1347, 'end': 1350, 'mesh': 'D006333'}, {'text': 'CHF', 'type': 'Disease', 'start': 1430, 'end': 1433, 'mesh': 'D006333'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 1683, 'end': 1699, 'mesh': 'D003520'}, {'text': 'CHF', 'type': 'Disease', 'start': 1716, 'end': 1719, 'mesh': 'D006333'}]"
+461,9746003,Inappropriate use of carbamazepine and vigabatrin in typical absence seizures.,"Carbamazepine and vigabatrin are contraindicated in typical absence seizures. Of 18 consecutive referrals of children with resistant typical absences only, eight were erroneously treated with carbamazepine either as monotherapy or as an add-on. Vigabatrin was also used in the treatment of two children. Frequency of absences increased in four children treated with carbamazepine and two of these developed myoclonic jerks, which resolved on withdrawal of carbamazepine. Absences were aggravated in both cases where vigabatrin was added on to concurrent treatment. Optimal control of the absences was achieved with sodium valproate, lamotrigine, or ethosuximide alone or in combination.","[{'text': 'carbamazepine', 'type': 'Chemical', 'start': 21, 'end': 34, 'mesh': 'D002220'}, {'text': 'vigabatrin', 'type': 'Chemical', 'start': 39, 'end': 49, 'mesh': 'D020888'}, {'text': 'absence seizures', 'type': 'Disease', 'start': 61, 'end': 77, 'mesh': 'D004832'}, {'text': 'Carbamazepine', 'type': 'Chemical', 'start': 79, 'end': 92, 'mesh': 'D002220'}, {'text': 'vigabatrin', 'type': 'Chemical', 'start': 97, 'end': 107, 'mesh': 'D020888'}, {'text': 'absence seizures', 'type': 'Disease', 'start': 139, 'end': 155, 'mesh': 'D004832'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 271, 'end': 284, 'mesh': 'D002220'}, {'text': 'Vigabatrin', 'type': 'Chemical', 'start': 324, 'end': 334, 'mesh': 'D020888'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 445, 'end': 458, 'mesh': 'D002220'}, {'text': 'myoclonic jerks', 'type': 'Disease', 'start': 486, 'end': 501, 'mesh': 'D009207'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 535, 'end': 548, 'mesh': 'D002220'}, {'text': 'vigabatrin', 'type': 'Chemical', 'start': 595, 'end': 605, 'mesh': 'D020888'}, {'text': 'sodium valproate', 'type': 'Chemical', 'start': 694, 'end': 710, 'mesh': 'D014635'}, {'text': 'lamotrigine', 'type': 'Chemical', 'start': 712, 'end': 723, 'mesh': 'C047781'}, {'text': 'ethosuximide', 'type': 'Chemical', 'start': 728, 'end': 740, 'mesh': 'D005013'}]"
+462,1992636,Hemolytic anemia associated with the use of omeprazole.,"Omeprazole is the first drug designed to block the final step in the acid secretory process within the parietal cell. It has been shown to be extremely effective in the treatment of peptic ulcer disease, reflux esophagitis, and the Zollinger-Ellison syndrome. Although clinical experience with omeprazole is still limited, many controlled studies have established the short-term safety of this drug. We report the first case of a serious short-term adverse reaction with the use of omeprazole: hemolytic anemia. The patient developed weakness, lethargy, and shortness of breath 2 days after starting therapy with omeprazole. Two weeks after the initiation of therapy, her hematocrit had decreased from 44.1% to 20.4%, and she had a positive direct Coombs antiglobulin test and an elevated indirect bilirubin. After she discontinued the omeprazole, her hemoglobin and hematocrit gradually returned to normal. The mechanism by which omeprazole caused the patient's hemolytic anemia is uncertain, but physicians should be alerted to this possible adverse effect.","[{'text': 'Hemolytic anemia', 'type': 'Disease', 'start': 0, 'end': 16, 'mesh': 'D000743'}, {'text': 'omeprazole', 'type': 'Chemical', 'start': 44, 'end': 54, 'mesh': 'D009853'}, {'text': 'Omeprazole', 'type': 'Chemical', 'start': 56, 'end': 66, 'mesh': 'D009853'}, {'text': 'peptic ulcer disease', 'type': 'Disease', 'start': 238, 'end': 258, 'mesh': 'D010437'}, {'text': 'reflux esophagitis', 'type': 'Disease', 'start': 260, 'end': 278, 'mesh': 'D005764'}, {'text': 'Zollinger-Ellison syndrome', 'type': 'Disease', 'start': 288, 'end': 314, 'mesh': 'D015043'}, {'text': 'omeprazole', 'type': 'Chemical', 'start': 350, 'end': 360, 'mesh': 'D009853'}, {'text': 'omeprazole', 'type': 'Chemical', 'start': 538, 'end': 548, 'mesh': 'D009853'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 550, 'end': 566, 'mesh': 'D000743'}, {'text': 'lethargy', 'type': 'Disease', 'start': 600, 'end': 608, 'mesh': 'D053609'}, {'text': 'shortness of breath', 'type': 'Disease', 'start': 614, 'end': 633, 'mesh': 'D004417'}, {'text': 'omeprazole', 'type': 'Chemical', 'start': 669, 'end': 679, 'mesh': 'D009853'}, {'text': 'bilirubin', 'type': 'Chemical', 'start': 854, 'end': 863, 'mesh': 'D001663'}, {'text': 'omeprazole', 'type': 'Chemical', 'start': 892, 'end': 902, 'mesh': 'D009853'}, {'text': 'omeprazole', 'type': 'Chemical', 'start': 987, 'end': 997, 'mesh': 'D009853'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 1019, 'end': 1035, 'mesh': 'D000743'}]"
+463,8387218,The use and toxicity of didanosine (ddI) in HIV antibody-positive individuals intolerant to zidovudine (AZT),"One hundred and fifty-one patients intolerant to zidovudine (AZT) received didanosine (ddI) to a maximum dose of 12.5 mg/kg/day. Patient response was assessed using changes in CD4+ lymphocyte subset count, HIV p24 antigen, weight, and quality of life. Seventy patients developed major opportunistic infections whilst on therapy; this was the first AIDS diagnosis in 17. Only minor changes in CD4+ lymphocyte subset count were observed in AIDS patients, although a more significant rise occurred in those with earlier stages of disease. Of those positive for p24 antigen at the commencement of the study 67% showed a positive response, and this was most likely in those with CD4+ lymphocyte subset counts above 100 mm3. A positive weight response was seen in 16% of patients. Most patients showed improvement in individual parameters and global score of quality of life. Adverse reactions possibly attributable to didanosine were common. The most common side-effect was diarrhoea, which resulted in cessation of therapy in 19 individuals. Peripheral neuropathy occurred in 12 patients and pancreatitis in six. Thirteen patients developed a raised serum amylase without abdominal pain. Seven patients developed glucose tolerance curves characteristic of diabetes but these were mild, did not require treatment and returned to normal on ceasing didanosine.","[{'text': 'toxicity', 'type': 'Disease', 'start': 12, 'end': 20, 'mesh': 'D064420'}, {'text': 'didanosine', 'type': 'Chemical', 'start': 24, 'end': 34, 'mesh': 'D016049'}, {'text': 'ddI', 'type': 'Chemical', 'start': 36, 'end': 39, 'mesh': 'D016049'}, {'text': 'HIV antibody-positive', 'type': 'Disease', 'start': 44, 'end': 65, 'mesh': 'D015658'}, {'text': 'zidovudine', 'type': 'Chemical', 'start': 92, 'end': 102, 'mesh': 'D015215'}, {'text': 'AZT', 'type': 'Chemical', 'start': 104, 'end': 107, 'mesh': 'D015215'}, {'text': 'zidovudine', 'type': 'Chemical', 'start': 158, 'end': 168, 'mesh': 'D015215'}, {'text': 'AZT', 'type': 'Chemical', 'start': 170, 'end': 173, 'mesh': 'D015215'}, {'text': 'didanosine', 'type': 'Chemical', 'start': 184, 'end': 194, 'mesh': 'D016049'}, {'text': 'ddI', 'type': 'Chemical', 'start': 196, 'end': 199, 'mesh': 'D016049'}, {'text': 'opportunistic infections', 'type': 'Disease', 'start': 394, 'end': 418, 'mesh': 'D009894'}, {'text': 'AIDS', 'type': 'Disease', 'start': 457, 'end': 461, 'mesh': 'D000163'}, {'text': 'AIDS', 'type': 'Disease', 'start': 547, 'end': 551, 'mesh': 'D000163'}, {'text': 'didanosine', 'type': 'Chemical', 'start': 1022, 'end': 1032, 'mesh': 'D016049'}, {'text': 'diarrhoea', 'type': 'Disease', 'start': 1078, 'end': 1087, 'mesh': 'D003967'}, {'text': 'Peripheral neuropathy', 'type': 'Disease', 'start': 1147, 'end': 1168, 'mesh': 'D010523'}, {'text': 'pancreatitis', 'type': 'Disease', 'start': 1197, 'end': 1209, 'mesh': 'D010195'}, {'text': 'abdominal pain', 'type': 'Disease', 'start': 1277, 'end': 1291, 'mesh': 'D015746'}, {'text': 'glucose tolerance curves', 'type': 'Disease', 'start': 1318, 'end': 1342, 'mesh': 'D018149'}, {'text': 'diabetes', 'type': 'Disease', 'start': 1361, 'end': 1369, 'mesh': 'D003920'}, {'text': 'didanosine', 'type': 'Chemical', 'start': 1451, 'end': 1461, 'mesh': 'D016049'}]"
+464,20698227,Can angiogenesis be a target of treatment for ribavirin associated hemolytic anemia?,"BACKGROUND/AIMS: Recently ribavirin has been found to inhibit angiogenesis and a number of angiogenesis inhibitors such as sunitinib and sorafenib have been found to cause acute hemolysis. We aimed to investigate whether there is a relation between hemoglobin, haptoglobin and angiogenesis soluble markers which are modifiable and can help in developing strategies against anemia. METHODS: Fourteen patients chronically infected with hepatitis C virus were treated by pegylated interferon alpha 2a and ribavirin. Serum hemoglobin, haptoglobin and angiogenesis markers of vascular endothelial growth factor and angiopoetin-2 were investigated before and after therapy. RESULTS: We observed a significant decrease in haptoglobin levels at the end of the treatment period. Hemoglobin levels also decreased but insignificantly by treatment. In contrast with the literature, serum levels of angiogenesis factors did not change significantly by pegylated interferon and ribavirin therapy. We found no correlation of angiogenesis soluble markers with either hemoglobin or haptoglobin. CONCLUSION: This is the first study in the literature investigating a link between angiogenesis soluble markers and ribavirin induced anemia in patients with hepatitis C and we could not find any relation. Future research with larger number of patients is needed to find out modifiable factors that will improve the safety of ribavirin therapy.","[{'text': 'ribavirin', 'type': 'Chemical', 'start': 46, 'end': 55, 'mesh': 'D012254'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 67, 'end': 83, 'mesh': 'D000743'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 111, 'end': 120, 'mesh': 'D012254'}, {'text': 'sunitinib', 'type': 'Chemical', 'start': 208, 'end': 217, 'mesh': 'C473478'}, {'text': 'sorafenib', 'type': 'Chemical', 'start': 222, 'end': 231, 'mesh': 'C471405'}, {'text': 'hemolysis', 'type': 'Disease', 'start': 263, 'end': 272, 'mesh': 'D006461'}, {'text': 'anemia', 'type': 'Disease', 'start': 458, 'end': 464, 'mesh': 'D000740'}, {'text': 'chronically infected with hepatitis C virus', 'type': 'Disease', 'start': 493, 'end': 536, 'mesh': 'D019698'}, {'text': 'pegylated interferon alpha 2a', 'type': 'Chemical', 'start': 553, 'end': 582, 'mesh': 'C100416'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 587, 'end': 596, 'mesh': 'D012254'}, {'text': 'pegylated interferon', 'type': 'Chemical', 'start': 1024, 'end': 1044, 'mesh': 'C417083'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 1049, 'end': 1058, 'mesh': 'D012254'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 1279, 'end': 1288, 'mesh': 'D012254'}, {'text': 'anemia', 'type': 'Disease', 'start': 1297, 'end': 1303, 'mesh': 'D000740'}, {'text': 'hepatitis C', 'type': 'Disease', 'start': 1321, 'end': 1332, 'mesh': 'D019698'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 1489, 'end': 1498, 'mesh': 'D012254'}]"
+465,20477932,"Cocaine causes memory and learning impairments in rats: involvement of nuclear factor kappa B and oxidative stress, and prevention by topiramate.","Different mechanisms have been suggested for cocaine toxicity including an increase in oxidative stress but the association between oxidative status in the brain and cocaine induced-behaviour is poorly understood. Nuclear factor kappa B (NFkappaB) is a sensor of oxidative stress and participates in memory formation that could be involved in drug toxicity and addiction mechanisms. Therefore NFkappaB activity, oxidative stress, neuronal nitric oxide synthase (nNOS) activity, spatial learning and memory as well as the effect of topiramate, a previously proposed therapy for cocaine addiction, were evaluated in an experimental model of cocaine administration in rats. NFkappaB activity was decreased in the frontal cortex of cocaine treated rats, as well as GSH concentration and glutathione peroxidase activity in the hippocampus, whereas nNOS activity in the hippocampus was increased. Memory retrieval of experiences acquired prior to cocaine administration was impaired and negatively correlated with NFkappaB activity in the frontal cortex. In contrast, learning of new tasks was enhanced and correlated with the increase of nNOS activity and the decrease of glutathione peroxidase. These results provide evidence for a possible mechanistic role of oxidative and nitrosative stress and NFkappaB in the alterations induced by cocaine. Topiramate prevented all the alterations observed, showing novel neuroprotective properties.","[{'text': 'Cocaine', 'type': 'Chemical', 'start': 0, 'end': 7, 'mesh': 'D003042'}, {'text': 'topiramate', 'type': 'Chemical', 'start': 134, 'end': 144, 'mesh': 'C052342'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 191, 'end': 198, 'mesh': 'D003042'}, {'text': 'toxicity', 'type': 'Disease', 'start': 199, 'end': 207, 'mesh': 'D064420'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 312, 'end': 319, 'mesh': 'D003042'}, {'text': 'toxicity', 'type': 'Disease', 'start': 494, 'end': 502, 'mesh': 'D064420'}, {'text': 'nitric oxide', 'type': 'Chemical', 'start': 585, 'end': 597, 'mesh': 'D009569'}, {'text': 'topiramate', 'type': 'Chemical', 'start': 677, 'end': 687, 'mesh': 'C052342'}, {'text': 'cocaine addiction', 'type': 'Disease', 'start': 723, 'end': 740, 'mesh': 'D019970'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 785, 'end': 792, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 874, 'end': 881, 'mesh': 'D003042'}, {'text': 'GSH', 'type': 'Chemical', 'start': 907, 'end': 910, 'mesh': 'D005978'}, {'text': 'glutathione', 'type': 'Chemical', 'start': 929, 'end': 940, 'mesh': 'D005978'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1087, 'end': 1094, 'mesh': 'D003042'}, {'text': 'glutathione', 'type': 'Chemical', 'start': 1313, 'end': 1324, 'mesh': 'D005978'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1479, 'end': 1486, 'mesh': 'D003042'}, {'text': 'Topiramate', 'type': 'Chemical', 'start': 1488, 'end': 1498, 'mesh': 'C052342'}]"
+466,9495837,Antinociceptive and antiamnesic properties of the presynaptic cholinergic amplifier PG-9.,"The antinociceptive effect of 3 alpha-tropyl 2-(p-bromophenyl)propionate [(+/-)-PG-9] (10-40 mg kg-1 s.c.; 30-60 mg kg-1 p.o.; 10-30 mg kg-1 i.v.; 10-30 micrograms/mouse i.c.v.) was examined in mice, rats and guinea pigs by use of the hot-plate, abdominal-constriction, tail-flick and paw-pressure tests. (+/-)-PG-9 antinociception peaked 15 min after injection and then slowly diminished. The antinociception produced by (+/-)-PG-9 was prevented by the unselective muscarinic antagonist atropine, the M1-selective antagonists pirenzepine and dicyclomine and the acetylcholine depletor hemicholinium-3, but not by the opioid antagonist naloxone, the gamma-aminobutyric acidB antagonist 3-aminopropyl-diethoxy-methyl-phosphinic acid, the H3 agonist R-(alpha)-methylhistamine, the D2 antagonist quinpirole, the 5-hydroxytryptamine4 antagonist 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride, the 5-hydroxytryptamin1A antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine hydrobromide and the polyamines depletor reserpine. Based on these data, it can be postulated that (+/-)-PG-9 exerted an antinociceptive effect mediated by a central potentiation of cholinergic transmission. (+/-)-PG-9 (10-40 mg kg-1 i.p.) was able to prevent amnesia induced by scopolamine (1 mg kg-1 i.p.) and dicyclomine (2 mg kg-1 i.p.) in the mouse passive-avoidance test. Affinity profiles of (+/-)-PG-9 for muscarinic receptor subtypes, determined by functional studies (rabbit vas deferens for M1, guinea pig atrium for M2, guinea pig ileum for M3 and immature guinea pig uterus for putative M4), have shown an M4/M1 selectivity ratio of 10.2 that might be responsible for the antinociception and the anti-amnesic effect induced by (+/-)-PG-9 through an increase in acetylcholine extracellular levels. In the antinociceptive and antiamnesic dose range, (+/-)-PG-9 did not impair mouse performance evaluated by the rota-rod test and Animex apparatus.","[{'text': 'PG-9', 'type': 'Chemical', 'start': 84, 'end': 88, 'mesh': 'C087567'}, {'text': '3 alpha-tropyl 2-(p-bromophenyl)propionate', 'type': 'Chemical', 'start': 120, 'end': 162, 'mesh': 'C087567'}, {'text': 'PG-9', 'type': 'Chemical', 'start': 170, 'end': 174, 'mesh': 'C087567'}, {'text': 'PG-9', 'type': 'Chemical', 'start': 401, 'end': 405, 'mesh': 'C087567'}, {'text': 'PG-9', 'type': 'Chemical', 'start': 518, 'end': 522, 'mesh': 'C087567'}, {'text': 'atropine', 'type': 'Chemical', 'start': 578, 'end': 586, 'mesh': 'D001285'}, {'text': 'pirenzepine', 'type': 'Chemical', 'start': 617, 'end': 628, 'mesh': 'D010890'}, {'text': 'dicyclomine', 'type': 'Chemical', 'start': 633, 'end': 644, 'mesh': 'D004025'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 653, 'end': 666, 'mesh': 'D000109'}, {'text': 'hemicholinium-3', 'type': 'Chemical', 'start': 676, 'end': 691, 'mesh': 'D006426'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 726, 'end': 734, 'mesh': 'D009270'}, {'text': 'gamma-aminobutyric acidB', 'type': 'Chemical', 'start': 740, 'end': 764, 'mesh': 'D005680'}, {'text': '3-aminopropyl-diethoxy-methyl-phosphinic acid', 'type': 'Chemical', 'start': 776, 'end': 821, 'mesh': 'C066430'}, {'text': 'R-(alpha)-methylhistamine', 'type': 'Chemical', 'start': 838, 'end': 863, 'mesh': 'C069357'}, {'text': 'quinpirole', 'type': 'Chemical', 'start': 883, 'end': 893, 'mesh': 'D019257'}, {'text': '5-hydroxytryptamine4', 'type': 'Chemical', 'start': 899, 'end': 919, 'mesh': 'D012701'}, {'text': '2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester', 'type': 'Chemical', 'start': 931, 'end': 997, 'mesh': 'C072790'}, {'text': '5-hydroxytryptamin1A', 'type': 'Chemical', 'start': 1017, 'end': 1037, 'mesh': 'D012701'}, {'text': '1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine', 'type': 'Chemical', 'start': 1049, 'end': 1105, 'mesh': 'C058895'}, {'text': 'reserpine', 'type': 'Chemical', 'start': 1147, 'end': 1156, 'mesh': 'D012110'}, {'text': 'PG-9', 'type': 'Chemical', 'start': 1211, 'end': 1215, 'mesh': 'C087567'}, {'text': 'PG-9', 'type': 'Chemical', 'start': 1320, 'end': 1324, 'mesh': 'C087567'}, {'text': 'amnesia', 'type': 'Disease', 'start': 1366, 'end': 1373, 'mesh': 'D000647'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 1385, 'end': 1396, 'mesh': 'D012601'}, {'text': 'dicyclomine', 'type': 'Chemical', 'start': 1418, 'end': 1429, 'mesh': 'D004025'}, {'text': 'PG-9', 'type': 'Chemical', 'start': 1511, 'end': 1515, 'mesh': 'C087567'}, {'text': 'amnesic', 'type': 'Disease', 'start': 1820, 'end': 1827, 'mesh': 'D000647'}, {'text': 'PG-9', 'type': 'Chemical', 'start': 1852, 'end': 1856, 'mesh': 'C087567'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 1880, 'end': 1893, 'mesh': 'D000109'}, {'text': 'PG-9', 'type': 'Chemical', 'start': 1973, 'end': 1977, 'mesh': 'C087567'}]"
+467,1468485,Hyperbaric oxygen therapy for control of intractable cyclophosphamide-induced hemorrhagic cystitis.,"We report a case of intractable hemorrhagic cystitis due to cyclophosphamide therapy for Wegener's granulomatosis. Conservative treatment, including bladder irrigation with physiological saline and instillation of prostaglandin F2 alpha, failed to totally control hemorrhage. We then used hyperbaric oxygen at an absolute pressure of 2 atm, 5 days a week for 8 consecutive weeks. The bleeding ceased completely by the end of treatment and the patient remained free of hematuria thereafter. No side effect was noted during the course of therapy. In future, this form of therapy can offer a safe alternative in the treatment of cyclophosphamide-induced hemorrhagic cystitis.","[{'text': 'oxygen', 'type': 'Chemical', 'start': 11, 'end': 17, 'mesh': 'D010100'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 53, 'end': 69, 'mesh': 'D003520'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 160, 'end': 176, 'mesh': 'D003520'}, {'text': ""Wegener's granulomatosis"", 'type': 'Disease', 'start': 189, 'end': 213, 'mesh': 'D014890'}, {'text': 'prostaglandin F2 alpha', 'type': 'Chemical', 'start': 314, 'end': 336, 'mesh': 'D015237'}, {'text': 'hemorrhage', 'type': 'Disease', 'start': 364, 'end': 374, 'mesh': 'D006470'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 400, 'end': 406, 'mesh': 'D010100'}, {'text': 'bleeding', 'type': 'Disease', 'start': 484, 'end': 492, 'mesh': 'D006470'}, {'text': 'hematuria', 'type': 'Disease', 'start': 568, 'end': 577, 'mesh': 'D006417'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 726, 'end': 742, 'mesh': 'D003520'}]"
+468,1009330,Further studies on effects of irrigation solutions on rat bladders.,Further studies on the effects of certain irrigating fluids on the rat bladder for 18 hours are reported. The results have shown that the degradation product p-choloroaniline is not a significant factor in chlorhexidine-digluconate associated erosive cystitis. A high percentage of kanamycin-colistin and povidone-iodine irrigations were associated with erosive cystitis and suggested a possible complication with human usage. Picloxydine irrigations appeared to have a lower incidence of erosive cystitis but further studies would have to be performed before it could be recommended for use in urological procedures.,"[{'text': 'p-choloroaniline', 'type': 'Chemical', 'start': 226, 'end': 242, 'mesh': 'C004658'}, {'text': 'chlorhexidine-digluconate', 'type': 'Chemical', 'start': 274, 'end': 299, 'mesh': 'C010882'}, {'text': 'cystitis', 'type': 'Disease', 'start': 319, 'end': 327, 'mesh': 'D003556'}, {'text': 'kanamycin', 'type': 'Chemical', 'start': 350, 'end': 359, 'mesh': 'D007612'}, {'text': 'colistin', 'type': 'Chemical', 'start': 360, 'end': 368, 'mesh': 'D003091'}, {'text': 'povidone-iodine', 'type': 'Chemical', 'start': 373, 'end': 388, 'mesh': 'D011206'}, {'text': 'cystitis', 'type': 'Disease', 'start': 430, 'end': 438, 'mesh': 'D003556'}, {'text': 'Picloxydine', 'type': 'Chemical', 'start': 495, 'end': 506, 'mesh': 'C005253'}, {'text': 'cystitis', 'type': 'Disease', 'start': 565, 'end': 573, 'mesh': 'D003556'}]"
+469,347884,Clinical experiences in an open and a double-blind trial.,"A total of sixty patients were trated with bromperidol first in open conditions (20 patients), then on a double blind basis (40 patients) with haloperidol as the reference substance. The open study lasted for four weeks; the drug was administrated in the form of 1 mg tablets. The daily dose (initial dose: 1 mg; mean dose at the end of the trial: 4.47 mg) was always administered in one single dose. Nineteen patients finished the trial, and in 18 cases the therapeutic result was considered very good to good. These results were confirmed by statistical analysis. Nine patients exhibited mild to moderate extrapyramidal concomitant symptoms; no other side effects were observed. The results of detailed laboratory tests and evaluations of various quantitative and qualitative tolerability parameters were not indicative of toxic effects. In the double blind study with haloperidol, both substances were found to be highly effective in the treatment of psychotic syndromes belonging predominantly to the schizophrenia group. Certain clues, including the onset of action, seem to be indicative of the superiority of bromperidol. No differences were observed with respect to side effects and general tolerability.","[{'text': 'bromperidol', 'type': 'Chemical', 'start': 101, 'end': 112, 'mesh': 'C006820'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 201, 'end': 212, 'mesh': 'D006220'}, {'text': 'extrapyramidal concomitant symptoms', 'type': 'Disease', 'start': 665, 'end': 700, 'mesh': 'D001480'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 929, 'end': 940, 'mesh': 'D006220'}, {'text': 'psychotic syndromes belonging predominantly to the schizophrenia group', 'type': 'Disease', 'start': 1012, 'end': 1082, 'mesh': 'D019967'}, {'text': 'bromperidol', 'type': 'Chemical', 'start': 1174, 'end': 1185, 'mesh': 'C006820'}]"
+470,20667451,Curcumin ameliorates cognitive dysfunction and oxidative damage in phenobarbitone and carbamazepine administered rats.,"The antiepileptic drugs, phenobarbitone and carbamazepine are well known to cause cognitive impairment on chronic use. The increase in free radical generation has been implicated as one of the important mechanisms of cognitive impairment by antiepileptic drugs. Curcumin has shown antioxidant, anti-inflammatory and neuro-protective properties. Therefore, the present study was carried out to investigate the effect of chronic curcumin administration on phenobarbitone- and carbamazepine-induced cognitive impairment and oxidative stress in rats. Pharmacokinetic interactions of curcumin with phenobarbitone and carbamazepine were also studied. Vehicle/drugs were administered daily for 21days to male Wistar rats. Passive avoidance paradigm and elevated plus maze test were used to assess cognitive function. At the end of study period, serum phenobarbitone and carbamazepine, whole brain malondialdehyde and reduced glutathione levels were estimated. The administration of phenobarbitone and carbamazepine for 21days caused a significant impairment of learning and memory as well as an increased oxidative stress. Concomitant curcumin administration prevented the cognitive impairment and decreased the increased oxidative stress induced by these antiepileptic drugs. Curcumin co-administration did not cause any significant alteration in the serum concentrations of both phenobarbitone as well as carbamazepine. These results show that curcumin has beneficial effect in mitigating the deterioration of cognitive functions and oxidative damage in rats treated with phenobarbitone and carbamazepine without significantly altering their serum concentrations. The findings suggest that curcumin can be considered as a potential safe and effective adjuvant to phenobarbitone and carbamazepine therapy in preventing cognitive impairment associated with these drugs.","[{'text': 'Curcumin', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D003474'}, {'text': 'cognitive dysfunction', 'type': 'Disease', 'start': 21, 'end': 42, 'mesh': 'D003072'}, {'text': 'phenobarbitone', 'type': 'Chemical', 'start': 67, 'end': 81, 'mesh': 'D010634'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 86, 'end': 99, 'mesh': 'D002220'}, {'text': 'phenobarbitone', 'type': 'Chemical', 'start': 144, 'end': 158, 'mesh': 'D010634'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 163, 'end': 176, 'mesh': 'D002220'}, {'text': 'cognitive impairment', 'type': 'Disease', 'start': 201, 'end': 221, 'mesh': 'D003072'}, {'text': 'cognitive impairment', 'type': 'Disease', 'start': 336, 'end': 356, 'mesh': 'D003072'}, {'text': 'Curcumin', 'type': 'Chemical', 'start': 381, 'end': 389, 'mesh': 'D003474'}, {'text': 'curcumin', 'type': 'Chemical', 'start': 546, 'end': 554, 'mesh': 'D003474'}, {'text': 'phenobarbitone', 'type': 'Chemical', 'start': 573, 'end': 587, 'mesh': 'D010634'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 593, 'end': 606, 'mesh': 'D002220'}, {'text': 'cognitive impairment', 'type': 'Disease', 'start': 615, 'end': 635, 'mesh': 'D003072'}, {'text': 'curcumin', 'type': 'Chemical', 'start': 698, 'end': 706, 'mesh': 'D003474'}, {'text': 'phenobarbitone', 'type': 'Chemical', 'start': 712, 'end': 726, 'mesh': 'D010634'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 731, 'end': 744, 'mesh': 'D002220'}, {'text': 'phenobarbitone', 'type': 'Chemical', 'start': 963, 'end': 977, 'mesh': 'D010634'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 982, 'end': 995, 'mesh': 'D002220'}, {'text': 'malondialdehyde', 'type': 'Chemical', 'start': 1009, 'end': 1024, 'mesh': 'D008315'}, {'text': 'glutathione', 'type': 'Chemical', 'start': 1037, 'end': 1048, 'mesh': 'D005978'}, {'text': 'phenobarbitone', 'type': 'Chemical', 'start': 1094, 'end': 1108, 'mesh': 'D010634'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 1113, 'end': 1126, 'mesh': 'D002220'}, {'text': 'impairment of learning and memory', 'type': 'Disease', 'start': 1159, 'end': 1192, 'mesh': 'D003072'}, {'text': 'curcumin', 'type': 'Chemical', 'start': 1247, 'end': 1255, 'mesh': 'D003474'}, {'text': 'cognitive impairment', 'type': 'Disease', 'start': 1285, 'end': 1305, 'mesh': 'D003072'}, {'text': 'Curcumin', 'type': 'Chemical', 'start': 1389, 'end': 1397, 'mesh': 'D003474'}, {'text': 'phenobarbitone', 'type': 'Chemical', 'start': 1493, 'end': 1507, 'mesh': 'D010634'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 1519, 'end': 1532, 'mesh': 'D002220'}, {'text': 'curcumin', 'type': 'Chemical', 'start': 1558, 'end': 1566, 'mesh': 'D003474'}, {'text': 'deterioration of cognitive functions', 'type': 'Disease', 'start': 1607, 'end': 1643, 'mesh': 'D003072'}, {'text': 'phenobarbitone', 'type': 'Chemical', 'start': 1686, 'end': 1700, 'mesh': 'D010634'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 1705, 'end': 1718, 'mesh': 'D002220'}, {'text': 'curcumin', 'type': 'Chemical', 'start': 1804, 'end': 1812, 'mesh': 'D003474'}, {'text': 'phenobarbitone', 'type': 'Chemical', 'start': 1877, 'end': 1891, 'mesh': 'D010634'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 1896, 'end': 1909, 'mesh': 'D002220'}, {'text': 'cognitive impairment', 'type': 'Disease', 'start': 1932, 'end': 1952, 'mesh': 'D003072'}]"
+471,19767176,Pyrrolidine dithiocarbamate protects the piriform cortex in the pilocarpine status epilepticus model.,"Pyrrolidine dithiocarbamate (PDTC) has a dual mechanism of action as an antioxidant and an inhibitor of the transcription factor kappa-beta. Both, production of reactive oxygen species as well as activation of NF-kappaB have been implicated in severe neuronal damage in different sub-regions of the hippocampus as well as in the surrounding cortices. The effect of PDTC on status epilepticus-associated cell loss in the hippocampus and piriform cortex was evaluated in the rat fractionated pilocarpine model. Treatment with 150 mg/kg PDTC before and following status epilepticus significantly increased the mortality rate to 100%. Administration of 50 mg/kg PDTC (low-dose) did not exert major effects on the development of a status epilepticus or the mortality rate. In vehicle-treated rats, status epilepticus caused pronounced neuronal damage in the piriform cortex comprising both pyramidal cells and interneurons. Low-dose PDTC treatment almost completely protected from lesions in the piriform cortex. A significant decrease in neuronal density of the hippocampal hilar formation was identified in vehicle- and PDTC-treated rats following status epilepticus. In conclusion, the NF-kappaB inhibitor and antioxidant PDTC protected the piriform cortex, whereas it did not affect hilar neuronal loss. These data might indicate that the generation of reactive oxygen species and activation of NF-kappaB plays a more central role in seizure-associated neuronal damage in the temporal cortex as compared to the hippocampal hilus. However, future investigations are necessary to exactly analyze the biochemical mechanisms by which PDTC exerted its beneficial effects in the piriform cortex.","[{'text': 'Pyrrolidine dithiocarbamate', 'type': 'Chemical', 'start': 0, 'end': 27, 'mesh': 'C020972'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 64, 'end': 75, 'mesh': 'D010862'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 76, 'end': 94, 'mesh': 'D013226'}, {'text': 'Pyrrolidine dithiocarbamate', 'type': 'Chemical', 'start': 102, 'end': 129, 'mesh': 'C020972'}, {'text': 'PDTC', 'type': 'Chemical', 'start': 131, 'end': 135, 'mesh': 'C020972'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 272, 'end': 278, 'mesh': 'D010100'}, {'text': 'neuronal damage', 'type': 'Disease', 'start': 353, 'end': 368, 'mesh': 'D009410'}, {'text': 'PDTC', 'type': 'Chemical', 'start': 467, 'end': 471, 'mesh': 'C020972'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 475, 'end': 493, 'mesh': 'D013226'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 592, 'end': 603, 'mesh': 'D010862'}, {'text': 'PDTC', 'type': 'Chemical', 'start': 636, 'end': 640, 'mesh': 'C020972'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 662, 'end': 680, 'mesh': 'D013226'}, {'text': 'PDTC', 'type': 'Chemical', 'start': 760, 'end': 764, 'mesh': 'C020972'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 828, 'end': 846, 'mesh': 'D013226'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 895, 'end': 913, 'mesh': 'D013226'}, {'text': 'neuronal damage', 'type': 'Disease', 'start': 932, 'end': 947, 'mesh': 'D009410'}, {'text': 'PDTC', 'type': 'Chemical', 'start': 1030, 'end': 1034, 'mesh': 'C020972'}, {'text': 'PDTC', 'type': 'Chemical', 'start': 1219, 'end': 1223, 'mesh': 'C020972'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 1247, 'end': 1265, 'mesh': 'D013226'}, {'text': 'PDTC', 'type': 'Chemical', 'start': 1322, 'end': 1326, 'mesh': 'C020972'}, {'text': 'neuronal loss', 'type': 'Disease', 'start': 1390, 'end': 1403, 'mesh': 'D009410'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 1463, 'end': 1469, 'mesh': 'D010100'}, {'text': 'seizure', 'type': 'Disease', 'start': 1535, 'end': 1542, 'mesh': 'D012640'}, {'text': 'neuronal damage', 'type': 'Disease', 'start': 1554, 'end': 1569, 'mesh': 'D009410'}, {'text': 'PDTC', 'type': 'Chemical', 'start': 1731, 'end': 1735, 'mesh': 'C020972'}]"
+472,16330293,"Safety profile of a nicotine lozenge compared with that of nicotine gum in adult smokers with underlying medical conditions: a 12-week, randomized, open-label study.","BACKGROUND: Nicotine polacrilex lozenges deliver 25% to 27% more nicotine compared with equivalent doses of nicotine polacrilex gum. The increased nicotine exposure from the lozenge has raised questions about the relative safety of the lozenge and gum. OBJECTIVE: The objective of this study was to compare the safety profiles of the 4-mg nicotine lozenge and 4-mg nicotine gum in smokers with selected label-restricted diseases. METHODS: This was a multicenter, randomized, open-label study in adult smokers with heart disease, hypertension not controlled by medication, and/or diabetes mellitus. Patients were randomized in a 1:1 ratio to receive the 4-mg nicotine lozenge or 4-mg nicotine gum. Safety assessments were made at baseline and at 2, 4, 6, and 12 weeks after the start of product use. RESULTS: Nine hundred one patients were randomized to treatment, 447 who received the lozenge and 454 who received the gum (safety population). The majority were women (52.7%). Patients' mean age was 53.9 years, their mean weight was 193.9 pounds, and they smoked a mean of 25.2 cigarettes per day at baseline. Five hundred fifty-three patients, 264 taking the lozenge and 289 taking the gum, used the study product for > or =4 days per week during the first 2 weeks (evaluable population). The nicotine lozenge and nicotine gum were equally well tolerated, despite increased nicotine exposure from the lozenge. The incidence of adverse events in the 2 groups was similar during the first 2 weeks of product use (evaluation population: 55.3% lozenge, 54.7% gum), as well as during the entire study (safety population: 63.8% and 58.6%, respectively). Stratification of patients by sex, age, extent of concurrent smoking, extent of product use, and severity of adverse events revealed no clinically significant differences between the lozenge and gum. The most common adverse events were nausea (17.2% and 16.1%; 95% CI, -3.7 to 6.0), hiccups (10.7% and 6.6%; 95% CI, 0.5 to 7.8), and headache (8.7% and 9.9%; 95% Cl, -5.0 to 2.6). Serious adverse events were reported in 11 and 13 patients in the respective groups. Fewer than 6% of patients in either group were considered by the investigator to have a worsening of their overall disease condition during the study. The majority of patients (>60%) experienced no change in their disease status from baseline. CONCLUSION: The 4-mg nicotine lozenge and 4-mg nicotine gum had comparable safety profiles in these patients with label-restricted medical conditions.","[{'text': 'nicotine', 'type': 'Chemical', 'start': 20, 'end': 28, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 59, 'end': 67, 'mesh': 'D009538'}, {'text': 'Nicotine', 'type': 'Chemical', 'start': 178, 'end': 186, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 231, 'end': 239, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 274, 'end': 282, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 313, 'end': 321, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 505, 'end': 513, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 531, 'end': 539, 'mesh': 'D009538'}, {'text': 'heart disease', 'type': 'Disease', 'start': 680, 'end': 693, 'mesh': 'D006331'}, {'text': 'hypertension', 'type': 'Disease', 'start': 695, 'end': 707, 'mesh': 'D006973'}, {'text': 'diabetes mellitus', 'type': 'Disease', 'start': 745, 'end': 762, 'mesh': 'D003920'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 824, 'end': 832, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 849, 'end': 857, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 1460, 'end': 1468, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 1481, 'end': 1489, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 1541, 'end': 1549, 'mesh': 'D009538'}, {'text': 'nausea', 'type': 'Disease', 'start': 2051, 'end': 2057, 'mesh': 'D009325'}, {'text': 'hiccups', 'type': 'Disease', 'start': 2098, 'end': 2105, 'mesh': 'D006606'}, {'text': 'headache', 'type': 'Disease', 'start': 2148, 'end': 2156, 'mesh': 'D006261'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 2545, 'end': 2553, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 2571, 'end': 2579, 'mesh': 'D009538'}]"
+473,14568327,Development of levodopa-induced dyskinesias in parkinsonian monkeys may depend upon rate of symptom onset and/or duration of symptoms.,"Levodopa-induced dyskinesias (LIDs) present a major problem for the long-term management of Parkinson's disease (PD) patients. Due to the interdependence of risk factors in clinical populations, it is difficult to independently examine factors that may influence the development of LIDs. Using macaque monkeys with different types of MPTP-induced parkinsonism, the current study evaluated the degree to which rate of symptom progression, symptom severity, and response to and duration of levodopa therapy may be involved in the development of LIDs. Monkeys with acute (short-term) MPTP exposure, rapid symptom onset and short symptom duration prior to initiation of levodopa therapy developed dyskinesia between 11 and 24 days of daily levodopa administration. In contrast, monkeys with long-term MPTP exposure, slow symptom progression and/or long symptom duration prior to initiation of levodopa therapy were more resistant to developing LIDs (e.g., dyskinesia developed no sooner than 146 days of chronic levodopa administration). All animals were similarly symptomatic at the start of levodopa treatment and had similar therapeutic responses to the drug. These data suggest distinct differences in the propensity to develop LIDs in monkeys with different rates of symptom progression or symptom durations prior to levodopa and demonstrate the value of these models for further studying the pathophysiology of LIDs.","[{'text': 'levodopa', 'type': 'Chemical', 'start': 15, 'end': 23, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 32, 'end': 43, 'mesh': 'D004409'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 47, 'end': 59, 'mesh': 'D010300'}, {'text': 'Levodopa', 'type': 'Chemical', 'start': 135, 'end': 143, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 152, 'end': 163, 'mesh': 'D004409'}, {'text': 'LIDs', 'type': 'Disease', 'start': 165, 'end': 169, 'mesh': 'D004409'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 227, 'end': 246, 'mesh': 'D010300'}, {'text': 'PD', 'type': 'Disease', 'start': 248, 'end': 250, 'mesh': 'D010300'}, {'text': 'LIDs', 'type': 'Disease', 'start': 417, 'end': 421, 'mesh': 'D004409'}, {'text': 'MPTP', 'type': 'Chemical', 'start': 469, 'end': 473, 'mesh': 'D015632'}, {'text': 'parkinsonism', 'type': 'Disease', 'start': 482, 'end': 494, 'mesh': 'D010302'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 623, 'end': 631, 'mesh': 'D007980'}, {'text': 'LIDs', 'type': 'Disease', 'start': 678, 'end': 682, 'mesh': 'D004409'}, {'text': 'MPTP', 'type': 'Chemical', 'start': 716, 'end': 720, 'mesh': 'D015632'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 801, 'end': 809, 'mesh': 'D007980'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 828, 'end': 838, 'mesh': 'D004409'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 871, 'end': 879, 'mesh': 'D007980'}, {'text': 'MPTP', 'type': 'Chemical', 'start': 932, 'end': 936, 'mesh': 'D015632'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1024, 'end': 1032, 'mesh': 'D007980'}, {'text': 'LIDs', 'type': 'Disease', 'start': 1075, 'end': 1079, 'mesh': 'D004409'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 1087, 'end': 1097, 'mesh': 'D004409'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1143, 'end': 1151, 'mesh': 'D007980'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1224, 'end': 1232, 'mesh': 'D007980'}, {'text': 'LIDs', 'type': 'Disease', 'start': 1363, 'end': 1367, 'mesh': 'D004409'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1453, 'end': 1461, 'mesh': 'D007980'}, {'text': 'LIDs', 'type': 'Disease', 'start': 1548, 'end': 1552, 'mesh': 'D004409'}]"
+474,11250767,Propylthiouracil-induced perinuclear-staining antineutrophil cytoplasmic autoantibody-positive vasculitis in conjunction with pericarditis.,"OBJECTIVE: To describe a case of propylthiouracil-induced vasculitis manifesting with pericarditis. METHODS: We present the first case report of a woman with hyperthyroidism treated with propylthiouracil in whom a syndrome of pericarditis, fever, and glomerulonephritis developed. Serologic testing and immunologic studies were done, and a pericardial biopsy was performed. RESULTS: A 25-year-old woman with Graves' disease had a febrile illness and evidence of pericarditis, which was confirmed by biopsy. Serologic evaluation revealed the presence of perinuclear-staining antineutrophil cytoplasmic autoantibodies (pANCA) against myeloperoxidase (MPO). Propylthiouracil therapy was withdrawn, and she was treated with a 1-month course of prednisone, which alleviated her symptoms. A literature review revealed no prior reports of pericarditis in anti-MPO pANCA-positive vasculitis associated with propylthio- uracil therapy. CONCLUSION: Pericarditis may be the initial manifestation of drug-induced vasculitis attributable to propylthio- uracil therapy.","[{'text': 'Propylthiouracil', 'type': 'Chemical', 'start': 0, 'end': 16, 'mesh': 'D011441'}, {'text': 'vasculitis', 'type': 'Disease', 'start': 95, 'end': 105, 'mesh': 'D014657'}, {'text': 'pericarditis', 'type': 'Disease', 'start': 126, 'end': 138, 'mesh': 'D010493'}, {'text': 'propylthiouracil', 'type': 'Chemical', 'start': 173, 'end': 189, 'mesh': 'D011441'}, {'text': 'vasculitis', 'type': 'Disease', 'start': 198, 'end': 208, 'mesh': 'D014657'}, {'text': 'pericarditis', 'type': 'Disease', 'start': 226, 'end': 238, 'mesh': 'D010493'}, {'text': 'hyperthyroidism', 'type': 'Disease', 'start': 298, 'end': 313, 'mesh': 'D006980'}, {'text': 'propylthiouracil', 'type': 'Chemical', 'start': 327, 'end': 343, 'mesh': 'D011441'}, {'text': 'pericarditis', 'type': 'Disease', 'start': 366, 'end': 378, 'mesh': 'D010493'}, {'text': 'fever', 'type': 'Disease', 'start': 380, 'end': 385, 'mesh': 'D005334'}, {'text': 'glomerulonephritis', 'type': 'Disease', 'start': 391, 'end': 409, 'mesh': 'D005921'}, {'text': ""Graves' disease"", 'type': 'Disease', 'start': 548, 'end': 563, 'mesh': 'D006111'}, {'text': 'febrile illness', 'type': 'Disease', 'start': 570, 'end': 585, 'mesh': 'D005334'}, {'text': 'pericarditis', 'type': 'Disease', 'start': 602, 'end': 614, 'mesh': 'D010493'}, {'text': 'Propylthiouracil', 'type': 'Chemical', 'start': 795, 'end': 811, 'mesh': 'D011441'}, {'text': 'prednisone', 'type': 'Chemical', 'start': 880, 'end': 890, 'mesh': 'D011241'}, {'text': 'pericarditis', 'type': 'Disease', 'start': 972, 'end': 984, 'mesh': 'D010493'}, {'text': 'vasculitis', 'type': 'Disease', 'start': 1012, 'end': 1022, 'mesh': 'D014657'}, {'text': 'propylthio- uracil', 'type': 'Chemical', 'start': 1039, 'end': 1057, 'mesh': 'D011441'}, {'text': 'Pericarditis', 'type': 'Disease', 'start': 1079, 'end': 1091, 'mesh': 'D010493'}, {'text': 'vasculitis', 'type': 'Disease', 'start': 1141, 'end': 1151, 'mesh': 'D014657'}, {'text': 'propylthio- uracil', 'type': 'Chemical', 'start': 1168, 'end': 1186, 'mesh': 'D011441'}]"
+475,11206082,Two mouse lines selected for differential sensitivities to beta-carboline-induced seizures are also differentially sensitive to various pharmacological effects of other GABA(A) receptor ligands.,"Two mouse lines were selectively bred according to their sensitivity (BS line) or resistance (BR line) to seizures induced by a single i.p. injection of methyl beta-carboline-3-carboxylate (beta-CCM), an inverse agonist of the GABA(A) receptor benzodiazepine site. Our aim was to characterize both lines' sensitivities to various physiological effects of other ligands of the GABA(A) receptor. We measured diazepam-induced anxiolysis with the elevated plus-maze test, diazepam-induced sedation by recording the vigilance states, and picrotoxin- and pentylenetetrazol-induced seizures after i.p. injections. Results presented here show that the differential sensitivities of BS and BR lines to beta-CCM can be extended to diazepam, picrotoxin, and pentylenetetrazol, suggesting a genetic selection of a general sensitivity and resistance to several ligands of the GABA(A) receptor.","[{'text': 'beta-carboline', 'type': 'Chemical', 'start': 59, 'end': 73, 'mesh': 'C036150'}, {'text': 'seizures', 'type': 'Disease', 'start': 82, 'end': 90, 'mesh': 'D012640'}, {'text': 'GABA', 'type': 'Chemical', 'start': 169, 'end': 173, 'mesh': 'D005680'}, {'text': 'seizures', 'type': 'Disease', 'start': 301, 'end': 309, 'mesh': 'D012640'}, {'text': 'methyl beta-carboline-3-carboxylate', 'type': 'Chemical', 'start': 348, 'end': 383, 'mesh': 'C036150'}, {'text': 'beta-CCM', 'type': 'Chemical', 'start': 385, 'end': 393, 'mesh': 'C036150'}, {'text': 'GABA', 'type': 'Chemical', 'start': 422, 'end': 426, 'mesh': 'D005680'}, {'text': 'benzodiazepine', 'type': 'Chemical', 'start': 439, 'end': 453, 'mesh': 'D001569'}, {'text': 'GABA', 'type': 'Chemical', 'start': 571, 'end': 575, 'mesh': 'D005680'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 601, 'end': 609, 'mesh': 'D003975'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 663, 'end': 671, 'mesh': 'D003975'}, {'text': 'picrotoxin', 'type': 'Chemical', 'start': 728, 'end': 738, 'mesh': 'D010852'}, {'text': 'pentylenetetrazol', 'type': 'Chemical', 'start': 744, 'end': 761, 'mesh': 'D010433'}, {'text': 'seizures', 'type': 'Disease', 'start': 770, 'end': 778, 'mesh': 'D012640'}, {'text': 'beta-CCM', 'type': 'Chemical', 'start': 888, 'end': 896, 'mesh': 'C036150'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 916, 'end': 924, 'mesh': 'D003975'}, {'text': 'picrotoxin', 'type': 'Chemical', 'start': 926, 'end': 936, 'mesh': 'D010852'}, {'text': 'pentylenetetrazol', 'type': 'Chemical', 'start': 942, 'end': 959, 'mesh': 'D010433'}, {'text': 'GABA', 'type': 'Chemical', 'start': 1058, 'end': 1062, 'mesh': 'D005680'}]"
+476,11027905,"Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized, controlled, double-blind, crossover, double-dose study.","Pain not responsive to morphine is often problematic. Animal and clinical studies have suggested that N-methyl-D-aspartate (NMDA) antagonists, such as ketamine, may be effective in improving opioid analgesia in difficult pain syndromes, such as neuropathic pain. A slow bolus of subhypnotic doses of ketamine (0.25 mg/kg or 0.50 mg/kg) was given to 10 cancer patients whose pain was unrelieved by morphine in a randomized, double-blind, crossover, double-dose study. Pain intensity on a 0 to 10 numerical scale; nausea and vomiting, drowsiness, confusion, and dry mouth, using a scale from 0 to 3 (not at all, slight, a lot, awful); Mini-Mental State Examination (MMSE) (0-30); and arterial pressure were recorded before administration of drugs (T0) and after 30 minutes (T30), 60 minutes (T60), 120 minutes (T120), and 180 minutes (T180). Ketamine, but not saline solution, significantly reduced the pain intensity in almost all the patients at both doses. This effect was more relevant in patients treated with higher doses. Hallucinations occurred in 4 patients, and an unpleasant sensation (""empty head"") was also reported by 2 patients. These episodes reversed after the administration of diazepam 1 mg intravenously. Significant increases in drowsiness were reported in patients treated with ketamine in both groups and were more marked with ketamine 0.50 mg/kg. A significant difference in MMSE was observed at T30 in patients who received 0.50 mg/kg of ketamine. Ketamine can improve morphine analgesia in difficult pain syndromes, such as neuropathic pain. However, the occurrence of central adverse effects should be taken into account, especially when using higher doses. This observation should be tested in studies of prolonged ketamine administration.","[{'text': 'ketamine', 'type': 'Chemical', 'start': 32, 'end': 40, 'mesh': 'D007649'}, {'text': 'cancer', 'type': 'Disease', 'start': 44, 'end': 50, 'mesh': 'D009369'}, {'text': 'morphine', 'type': 'Chemical', 'start': 63, 'end': 71, 'mesh': 'D009020'}, {'text': 'Pain', 'type': 'Disease', 'start': 151, 'end': 155, 'mesh': 'D010146'}, {'text': 'morphine', 'type': 'Chemical', 'start': 174, 'end': 182, 'mesh': 'D009020'}, {'text': 'N-methyl-D-aspartate', 'type': 'Chemical', 'start': 253, 'end': 273, 'mesh': 'D016202'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 275, 'end': 279, 'mesh': 'D016202'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 302, 'end': 310, 'mesh': 'D007649'}, {'text': 'pain', 'type': 'Disease', 'start': 372, 'end': 376, 'mesh': 'D010146'}, {'text': 'neuropathic pain', 'type': 'Disease', 'start': 396, 'end': 412, 'mesh': 'D009437'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 451, 'end': 459, 'mesh': 'D007649'}, {'text': 'cancer', 'type': 'Disease', 'start': 503, 'end': 509, 'mesh': 'D009369'}, {'text': 'pain', 'type': 'Disease', 'start': 525, 'end': 529, 'mesh': 'D010146'}, {'text': 'morphine', 'type': 'Chemical', 'start': 548, 'end': 556, 'mesh': 'D009020'}, {'text': 'Pain', 'type': 'Disease', 'start': 618, 'end': 622, 'mesh': 'D010146'}, {'text': 'nausea', 'type': 'Disease', 'start': 663, 'end': 669, 'mesh': 'D009325'}, {'text': 'vomiting', 'type': 'Disease', 'start': 674, 'end': 682, 'mesh': 'D014839'}, {'text': 'confusion', 'type': 'Disease', 'start': 696, 'end': 705, 'mesh': 'D003221'}, {'text': 'dry mouth', 'type': 'Disease', 'start': 711, 'end': 720, 'mesh': 'D014987'}, {'text': 'Ketamine', 'type': 'Chemical', 'start': 991, 'end': 999, 'mesh': 'D007649'}, {'text': 'pain', 'type': 'Disease', 'start': 1052, 'end': 1056, 'mesh': 'D010146'}, {'text': 'Hallucinations', 'type': 'Disease', 'start': 1178, 'end': 1192, 'mesh': 'D006212'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 1345, 'end': 1353, 'mesh': 'D003975'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 1449, 'end': 1457, 'mesh': 'D007649'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 1499, 'end': 1507, 'mesh': 'D007649'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 1612, 'end': 1620, 'mesh': 'D007649'}, {'text': 'Ketamine', 'type': 'Chemical', 'start': 1622, 'end': 1630, 'mesh': 'D007649'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1643, 'end': 1651, 'mesh': 'D009020'}, {'text': 'pain', 'type': 'Disease', 'start': 1675, 'end': 1679, 'mesh': 'D010146'}, {'text': 'neuropathic pain', 'type': 'Disease', 'start': 1699, 'end': 1715, 'mesh': 'D009437'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 1892, 'end': 1900, 'mesh': 'D007649'}]"
+477,9334596,"Endocrine screening in 1,022 men with erectile dysfunction: clinical significance and cost-effective strategy.","PURPOSE: We reviewed the results of serum testosterone and prolactin determination in 1,022 patients referred because of erectile dysfunction and compared the data with history, results of physical examination, other etiological investigations and effects of endocrine therapy to refine the rules of cost-effective endocrine screening and to pinpoint actual responsibility for hormonal abnormalities. MATERIALS AND METHODS: Testosterone and prolactin were determined by radioimmunoassay. Every patient was screened for testosterone and 451 were screened for prolactin on the basis of low sexual desire, gynecomastia or testosterone less than 4 ng./ml. Determination was repeated in case of abnormal first results. Prolactin results were compared with those of a previous personal cohort of 1,340 patients with erectile dysfunction and systematic prolactin determination. Main clinical criteria tested regarding efficiency in hormone determination were low sexual desire, small testes and gynecomastia. Endocrine therapy consisted of testosterone heptylate or human chorionic gonadotropin for hypogonadism and bromocriptine for hyperprolactinemia. RESULTS: Testosterone was less than 3 ng./ml. in 107 patients but normal in 40% at repeat determination. The prevalence of repeatedly low testosterone increased with age (4% before age 50 years and 9% 50 years or older). Two pituitary tumors were discovered after testosterone determination. Most of the other low testosterone levels seemed to result from nonorganic hypothalamic dysfunction because of normal serum luteinizing hormone and prolactin and to have only a small role in erectile dysfunction (definite improvement in only 16 of 44 [36%] after androgen therapy, normal morning or nocturnal erections in 30% and definite vasculogenic contributions in 42%). Determining testosterone only in cases of low sexual desire or abnormal physical examination would have missed 40% of the cases with low testosterone, including 37% of those subsequently improved by androgen therapy. Prolactin exceeded 20 ng./ml. in 5 men and was normal in 2 at repeat determination. Only 1 prolactinoma was discovered. These data are lower than those we found during the last 2 decades (overall prolactin greater than 20 ng./ml. in 1.86% of 1,821 patients, prolactinomas in 7, 0.38%). Bromocriptine was definitely effective in cases with prolactin greater than 35 ng./ml. (8 of 12 compared to only 9 of 22 cases with prolactin between 20 and 35 ng./ml.). Testosterone was low in less than 50% of cases with prolactin greater than 35 ng./ml. CONCLUSIONS: Low prevalences and effects of low testosterone and high prolactin in erectile dysfunction cannot justify their routine determination. However, cost-effective screening strategies recommended so far missed 40 to 50% of cases improved with endocrine therapy and the pituitary tumors. We now advocate that before age 50 years testosterone be determined only in cases of low sexual desire and abnormal physical examination but that it be measured in all men older than 50 years. Prolactin should be determined only in cases of low sexual desire, gynecomastia and/or testosterone less than 4 ng./ml.","[{'text': 'erectile dysfunction', 'type': 'Disease', 'start': 38, 'end': 58, 'mesh': 'D007172'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 153, 'end': 165, 'mesh': 'D013739'}, {'text': 'erectile dysfunction', 'type': 'Disease', 'start': 232, 'end': 252, 'mesh': 'D007172'}, {'text': 'Testosterone', 'type': 'Chemical', 'start': 535, 'end': 547, 'mesh': 'D013739'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 630, 'end': 642, 'mesh': 'D013739'}, {'text': 'low sexual desire', 'type': 'Disease', 'start': 695, 'end': 712, 'mesh': 'D020018'}, {'text': 'gynecomastia', 'type': 'Disease', 'start': 714, 'end': 726, 'mesh': 'D006177'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 730, 'end': 742, 'mesh': 'D013739'}, {'text': 'erectile dysfunction', 'type': 'Disease', 'start': 921, 'end': 941, 'mesh': 'D007172'}, {'text': 'low sexual desire', 'type': 'Disease', 'start': 1063, 'end': 1080, 'mesh': 'D020018'}, {'text': 'gynecomastia', 'type': 'Disease', 'start': 1099, 'end': 1111, 'mesh': 'D006177'}, {'text': 'testosterone heptylate', 'type': 'Chemical', 'start': 1144, 'end': 1166, 'mesh': 'C004648'}, {'text': 'hypogonadism', 'type': 'Disease', 'start': 1203, 'end': 1215, 'mesh': 'D007006'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 1220, 'end': 1233, 'mesh': 'D001971'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 1238, 'end': 1256, 'mesh': 'D006966'}, {'text': 'Testosterone', 'type': 'Chemical', 'start': 1267, 'end': 1279, 'mesh': 'D013739'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 1396, 'end': 1408, 'mesh': 'D013739'}, {'text': 'pituitary tumors', 'type': 'Disease', 'start': 1483, 'end': 1499, 'mesh': 'D010911'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 1522, 'end': 1534, 'mesh': 'D013739'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 1572, 'end': 1584, 'mesh': 'D013739'}, {'text': 'hypothalamic dysfunction', 'type': 'Disease', 'start': 1625, 'end': 1649, 'mesh': 'D007027'}, {'text': 'erectile dysfunction', 'type': 'Disease', 'start': 1741, 'end': 1761, 'mesh': 'D007172'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 1937, 'end': 1949, 'mesh': 'D013739'}, {'text': 'low sexual desire', 'type': 'Disease', 'start': 1967, 'end': 1984, 'mesh': 'D020018'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 2062, 'end': 2074, 'mesh': 'D013739'}, {'text': 'prolactinoma', 'type': 'Disease', 'start': 2233, 'end': 2245, 'mesh': 'D015175'}, {'text': 'prolactinomas', 'type': 'Disease', 'start': 2400, 'end': 2413, 'mesh': 'D015175'}, {'text': 'Bromocriptine', 'type': 'Chemical', 'start': 2428, 'end': 2441, 'mesh': 'D001971'}, {'text': 'Testosterone', 'type': 'Chemical', 'start': 2598, 'end': 2610, 'mesh': 'D013739'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 2732, 'end': 2744, 'mesh': 'D013739'}, {'text': 'erectile dysfunction', 'type': 'Disease', 'start': 2767, 'end': 2787, 'mesh': 'D007172'}, {'text': 'pituitary tumors', 'type': 'Disease', 'start': 2962, 'end': 2978, 'mesh': 'D010911'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 3021, 'end': 3033, 'mesh': 'D013739'}, {'text': 'low sexual desire', 'type': 'Disease', 'start': 3065, 'end': 3082, 'mesh': 'D020018'}, {'text': 'low sexual desire', 'type': 'Disease', 'start': 3221, 'end': 3238, 'mesh': 'D020018'}, {'text': 'gynecomastia', 'type': 'Disease', 'start': 3240, 'end': 3252, 'mesh': 'D006177'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 3260, 'end': 3272, 'mesh': 'D013739'}]"
+478,8595686,Thiopentone pretreatment for propofol injection pain in ambulatory patients.,"This study investigated propofol injection pain in patients undergoing ambulatory anaesthesia. In a randomized, double-blind trial, 90 women were allocated to receive one of three treatments prior to induction of anaesthesia with propofol. Patients in Group C received 2 ml normal saline, Group L, 2 ml, lidocaine 2% (40 mg) and Group T, 2 ml thiopentone 2.5% (50 mg). Venous discomfort was assessed with a visual analogue scale (VAS) 5-15 sec after commencing propofol administration using an infusion pump (rate 1000 micrograms.kg-1.min-1). Loss of consciousness occurred in 60-90 sec. Visual analogue scores (mean +/- SD) during induction were lower in Groups L (3.3 +/- 2.5) and T (4.1 +/- 2.7) than in Group C (5.6 +/- 2.3); P = 0.0031. The incidence of venous discomfort was lower in Group L (76.6%; P < 0.05) than in Group C (100%) but not different from Group T (90%). The VAS scores for recall of pain in the recovery room were correlated with the VAS scores during induction (r = 0.7045; P < 0.0001). Recovery room discharge times were similar: C (75.9 +/- 19.4 min); L 73.6 +/- 21.6 min); T (77.1 +/- 18.9 min). Assessing their overall satisfaction, 89.7% would choose propofol anaesthesia again. We conclude that lidocaine reduces the incidence and severity of propofol injection pain in ambulatory patients whereas thiopentone only reduces its severity.","[{'text': 'Thiopentone', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D013874'}, {'text': 'propofol', 'type': 'Chemical', 'start': 29, 'end': 37, 'mesh': 'D015742'}, {'text': 'pain', 'type': 'Disease', 'start': 48, 'end': 52, 'mesh': 'D010146'}, {'text': 'propofol', 'type': 'Chemical', 'start': 101, 'end': 109, 'mesh': 'D015742'}, {'text': 'pain', 'type': 'Disease', 'start': 120, 'end': 124, 'mesh': 'D010146'}, {'text': 'propofol', 'type': 'Chemical', 'start': 307, 'end': 315, 'mesh': 'D015742'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 381, 'end': 390, 'mesh': 'D008012'}, {'text': 'thiopentone', 'type': 'Chemical', 'start': 420, 'end': 431, 'mesh': 'D013874'}, {'text': 'propofol', 'type': 'Chemical', 'start': 538, 'end': 546, 'mesh': 'D015742'}, {'text': 'Loss of consciousness', 'type': 'Disease', 'start': 620, 'end': 641, 'mesh': 'D014474'}, {'text': 'pain', 'type': 'Disease', 'start': 983, 'end': 987, 'mesh': 'D010146'}, {'text': 'propofol', 'type': 'Chemical', 'start': 1257, 'end': 1265, 'mesh': 'D015742'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 1302, 'end': 1311, 'mesh': 'D008012'}, {'text': 'propofol', 'type': 'Chemical', 'start': 1350, 'end': 1358, 'mesh': 'D015742'}, {'text': 'pain', 'type': 'Disease', 'start': 1369, 'end': 1373, 'mesh': 'D010146'}, {'text': 'thiopentone', 'type': 'Chemical', 'start': 1405, 'end': 1416, 'mesh': 'D013874'}]"
+479,6466532,Comparison of i.v. glycopyrrolate and atropine in the prevention of bradycardia and arrhythmias following repeated doses of suxamethonium in children.,"The effectiveness of administration of glycopyrrolate 5 and 10 micrograms kg-1 and atropine 10 and 20 micrograms kg-1 i.v. immediately before the induction of anaesthesia, to prevent arrhythmia and bradycardia following repeated doses of suxamethonium in children, was studied. A control group was included for comparison with the lower dose range of glycopyrrolate and atropine. A frequency of bradycardia of 50% was noted in the control group, but this was not significantly different from the frequency with the active drugs. Bradycardia (defined as a decrease in heart rate to less than 50 beat min-1) was prevented when the larger dose of either active drug was used. It is recommended that either glycopyrrolate 10 micrograms kg-1 or atropine 20 micrograms kg-1 i.v. should immediately precede induction of anaesthesia, in children, if the repeated administration of suxamethonium is anticipated.","[{'text': 'glycopyrrolate', 'type': 'Chemical', 'start': 19, 'end': 33, 'mesh': 'D006024'}, {'text': 'atropine', 'type': 'Chemical', 'start': 38, 'end': 46, 'mesh': 'D001285'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 68, 'end': 79, 'mesh': 'D001919'}, {'text': 'arrhythmias', 'type': 'Disease', 'start': 84, 'end': 95, 'mesh': 'D001145'}, {'text': 'suxamethonium', 'type': 'Chemical', 'start': 124, 'end': 137, 'mesh': 'D013390'}, {'text': 'glycopyrrolate', 'type': 'Chemical', 'start': 190, 'end': 204, 'mesh': 'D006024'}, {'text': 'atropine', 'type': 'Chemical', 'start': 234, 'end': 242, 'mesh': 'D001285'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 334, 'end': 344, 'mesh': 'D001145'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 349, 'end': 360, 'mesh': 'D001919'}, {'text': 'suxamethonium', 'type': 'Chemical', 'start': 389, 'end': 402, 'mesh': 'D013390'}, {'text': 'glycopyrrolate', 'type': 'Chemical', 'start': 502, 'end': 516, 'mesh': 'D006024'}, {'text': 'atropine', 'type': 'Chemical', 'start': 521, 'end': 529, 'mesh': 'D001285'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 546, 'end': 557, 'mesh': 'D001919'}, {'text': 'Bradycardia', 'type': 'Disease', 'start': 680, 'end': 691, 'mesh': 'D001919'}, {'text': 'glycopyrrolate', 'type': 'Chemical', 'start': 854, 'end': 868, 'mesh': 'D006024'}, {'text': 'atropine', 'type': 'Chemical', 'start': 891, 'end': 899, 'mesh': 'D001285'}, {'text': 'suxamethonium', 'type': 'Chemical', 'start': 1024, 'end': 1037, 'mesh': 'D013390'}]"
+480,6308277,Reduction in caffeine toxicity by acetaminophen.,"A patient who allegedly consumed 100 tablets of an over-the-counter analgesic containing sodium acetylsalicylate, caffeine, and acetaminophen displayed no significant CNS stimulation despite the presence of 175 micrograms of caffeine per mL of serum. Because salicylates have been reported to augment the stimulatory effects of caffeine on the CNS, attention was focused on the possibility that the presence of acetaminophen (52 micrograms/mL) reduced the CNS toxicity of caffeine. Studies in DBA/2J mice showed that: 1) pretreatment with acetaminophen (100 mg/kg) increased the interval between the administration of caffeine (300 to 450 mg/kg IP) and the onset of fatal convulsions by a factor of about two; and 2) pretreatment with acetaminophen (75 mg/kg) reduced the incidence of audiogenic seizures produced in the presence of caffeine (12.5 to 75 mg/kg IP). The frequency of sound-induced seizures after 12.5 or 25 mg/kg caffeine was reduced from 50 to 5% by acetaminophen. In the absence of caffeine, acetaminophen (up to 300 mg/kg) did not modify the seizures induced by maximal electroshock and did not alter the convulsant dose of pentylenetetrezol in mice (tests performed by the Anticonvulsant Screening Project of NINCDS). Acetaminophen (up to 150 micrograms/mL) did not retard the incorporation of radioactive adenosine into ATP in slices of rat cerebral cortex. Thus the mechanism by which acetaminophen antagonizes the actions of caffeine in the CNS remains unknown.","[{'text': 'caffeine', 'type': 'Chemical', 'start': 13, 'end': 21, 'mesh': 'D002110'}, {'text': 'toxicity', 'type': 'Disease', 'start': 22, 'end': 30, 'mesh': 'D064420'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 34, 'end': 47, 'mesh': 'D000082'}, {'text': 'sodium acetylsalicylate', 'type': 'Chemical', 'start': 138, 'end': 161, 'mesh': '-1'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 163, 'end': 171, 'mesh': 'D002110'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 177, 'end': 190, 'mesh': 'D000082'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 274, 'end': 282, 'mesh': 'D002110'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 377, 'end': 385, 'mesh': 'D002110'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 460, 'end': 473, 'mesh': 'D000082'}, {'text': 'toxicity', 'type': 'Disease', 'start': 509, 'end': 517, 'mesh': 'D064420'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 521, 'end': 529, 'mesh': 'D002110'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 588, 'end': 601, 'mesh': 'D000082'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 667, 'end': 675, 'mesh': 'D002110'}, {'text': 'convulsions', 'type': 'Disease', 'start': 721, 'end': 732, 'mesh': 'D012640'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 784, 'end': 797, 'mesh': 'D000082'}, {'text': 'seizures', 'type': 'Disease', 'start': 845, 'end': 853, 'mesh': 'D012640'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 882, 'end': 890, 'mesh': 'D002110'}, {'text': 'seizures', 'type': 'Disease', 'start': 945, 'end': 953, 'mesh': 'D012640'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 977, 'end': 985, 'mesh': 'D002110'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 1015, 'end': 1028, 'mesh': 'D000082'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1048, 'end': 1056, 'mesh': 'D002110'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 1058, 'end': 1071, 'mesh': 'D000082'}, {'text': 'seizures', 'type': 'Disease', 'start': 1109, 'end': 1117, 'mesh': 'D012640'}, {'text': 'pentylenetetrezol', 'type': 'Chemical', 'start': 1191, 'end': 1208, 'mesh': 'D010433'}, {'text': 'Acetaminophen', 'type': 'Chemical', 'start': 1286, 'end': 1299, 'mesh': 'D000082'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 1374, 'end': 1383, 'mesh': 'D000241'}, {'text': 'ATP', 'type': 'Chemical', 'start': 1389, 'end': 1392, 'mesh': 'D000255'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 1455, 'end': 1468, 'mesh': 'D000082'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1496, 'end': 1504, 'mesh': 'D002110'}]"
+481,2870085,Flestolol: an ultra-short-acting beta-adrenergic blocking agent.,"Flestolol (ACC-9089) is a nonselective, competitive, ultra-short-acting beta-adrenergic blocking agent, without any intrinsic sympathomimetic activity. Flestolol is metabolized by plasma esterases and has an elimination half-life of approximately 6.5 minutes. This agent was well tolerated in healthy volunteers at doses up to 100 micrograms/kg/min. In long-term infusion studies, flestolol was well tolerated at the effective beta-blocking dose (5 micrograms/kg/min) for up to seven days. Flestolol blood concentrations increased linearly with increasing dose and good correlation exists between blood concentrations of flestolol and beta-adrenergic blockade. Flestolol produced a dose-dependent attenuation of isoproterenol-induced tachycardia. Electrophysiologic and hemodynamic effects of flestolol are similar to those of other beta blockers. In contrast with other beta blockers, flestolol-induced effects reverse rapidly (within 30 minutes) following discontinuation because of its short half-life. Flestolol effectively reduced heart rate in patients with supraventricular tachyarrhythmia. In patients with unstable angina, flestolol infusion was found to be safe and effective in controlling chest pain. It is concluded that flestolol is a potent, well-tolerated, ultra-short-acting beta-adrenergic blocking agent. Use of flestolol in the critical care setting is currently undergoing investigation.","[{'text': 'Flestolol', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'C047847'}, {'text': 'Flestolol', 'type': 'Chemical', 'start': 65, 'end': 74, 'mesh': 'C047847'}, {'text': 'ACC-9089', 'type': 'Chemical', 'start': 76, 'end': 84, 'mesh': 'C047847'}, {'text': 'Flestolol', 'type': 'Chemical', 'start': 217, 'end': 226, 'mesh': 'C047847'}, {'text': 'flestolol', 'type': 'Chemical', 'start': 446, 'end': 455, 'mesh': 'C047847'}, {'text': 'Flestolol', 'type': 'Chemical', 'start': 555, 'end': 564, 'mesh': 'C047847'}, {'text': 'flestolol', 'type': 'Chemical', 'start': 686, 'end': 695, 'mesh': 'C047847'}, {'text': 'Flestolol', 'type': 'Chemical', 'start': 726, 'end': 735, 'mesh': 'C047847'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 777, 'end': 790, 'mesh': 'D007545'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 799, 'end': 810, 'mesh': 'D013610'}, {'text': 'flestolol', 'type': 'Chemical', 'start': 858, 'end': 867, 'mesh': 'C047847'}, {'text': 'flestolol', 'type': 'Chemical', 'start': 951, 'end': 960, 'mesh': 'C047847'}, {'text': 'Flestolol', 'type': 'Chemical', 'start': 1071, 'end': 1080, 'mesh': 'C047847'}, {'text': 'supraventricular tachyarrhythmia', 'type': 'Disease', 'start': 1129, 'end': 1161, 'mesh': 'D013617'}, {'text': 'unstable angina', 'type': 'Disease', 'start': 1180, 'end': 1195, 'mesh': 'D000789'}, {'text': 'flestolol', 'type': 'Chemical', 'start': 1197, 'end': 1206, 'mesh': 'C047847'}, {'text': 'chest pain', 'type': 'Disease', 'start': 1266, 'end': 1276, 'mesh': 'D002637'}, {'text': 'flestolol', 'type': 'Chemical', 'start': 1299, 'end': 1308, 'mesh': 'C047847'}, {'text': 'flestolol', 'type': 'Chemical', 'start': 1396, 'end': 1405, 'mesh': 'C047847'}]"
+482,1639466,Adverse effect of the calcium channel blocker nitrendipine on nephrosclerosis in rats with renovascular hypertension.,"The effect of a 6-week treatment with the calcium channel blocker nitrendipine or the angiotensin converting enzyme inhibitor enalapril on blood pressure, albuminuria, renal hemodynamics, and morphology of the nonclipped kidney was studied in rats with two-kidney, one clip renovascular hypertension. Six weeks after clipping of one renal artery, hypertensive rats (178 +/- 4 mm Hg) were randomly assigned to three groups: untreated hypertensive controls (n = 8), enalapril-treated (n = 8), or nitrendipine-treated (n = 10). Sham-operated rats served as normotensive controls (128 +/- 3 mm Hg, n = 8). After 6 weeks of treatment, renal hemodynamics (glomerular filtration rate and renal plasma flow) were measured in the anesthetized rats. Renal tissue was obtained for determination of glomerular size and sclerosis. Enalapril but not nitrendipine reduced blood pressure significantly. After 6 weeks of therapy, glomerular filtration rate was not different among the studied groups. Renal plasma flow increased, but albumin excretion and glomerulosclerosis did not change after enalapril treatment. In contrast, in the nitrendipine-treated group albuminuria increased from 12.8 +/- 2 progressively to 163 +/- 55 compared with 19.2 +/- 9 mg/24 hr in the hypertensive controls. Furthermore, glomerulosclerosis index was significantly increased in the nitrendipine-treated group compared with the hypertensive controls (0.38 +/- 0.1 versus 0.13 +/- 0.04). In addition, glomerular size was higher in the nitrendipine-treated group (14.9 +/- 0.17 10(-3) mm2) but lower in the enalapril-treated group (11.5 +/- 0.15 10(-3) mm2) compared with the hypertensive controls (12.1 +/- 0.17 10(-3) mm2).(ABSTRACT TRUNCATED AT 250 WORDS)","[{'text': 'calcium', 'type': 'Chemical', 'start': 22, 'end': 29, 'mesh': 'D002118'}, {'text': 'nitrendipine', 'type': 'Chemical', 'start': 46, 'end': 58, 'mesh': 'D009568'}, {'text': 'nephrosclerosis', 'type': 'Disease', 'start': 62, 'end': 77, 'mesh': 'D009400'}, {'text': 'renovascular hypertension', 'type': 'Disease', 'start': 91, 'end': 116, 'mesh': 'D006978'}, {'text': 'calcium', 'type': 'Chemical', 'start': 160, 'end': 167, 'mesh': 'D002118'}, {'text': 'nitrendipine', 'type': 'Chemical', 'start': 184, 'end': 196, 'mesh': 'D009568'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 204, 'end': 215, 'mesh': 'D000809'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 244, 'end': 253, 'mesh': 'D004656'}, {'text': 'albuminuria', 'type': 'Disease', 'start': 273, 'end': 284, 'mesh': 'D000419'}, {'text': 'renovascular hypertension', 'type': 'Disease', 'start': 392, 'end': 417, 'mesh': 'D006978'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 465, 'end': 477, 'mesh': 'D006973'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 551, 'end': 563, 'mesh': 'D006973'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 582, 'end': 591, 'mesh': 'D004656'}, {'text': 'nitrendipine', 'type': 'Chemical', 'start': 612, 'end': 624, 'mesh': 'D009568'}, {'text': 'Enalapril', 'type': 'Chemical', 'start': 936, 'end': 945, 'mesh': 'D004656'}, {'text': 'nitrendipine', 'type': 'Chemical', 'start': 954, 'end': 966, 'mesh': 'D009568'}, {'text': 'glomerulosclerosis', 'type': 'Disease', 'start': 1157, 'end': 1175, 'mesh': 'D005921'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 1197, 'end': 1206, 'mesh': 'D004656'}, {'text': 'nitrendipine', 'type': 'Chemical', 'start': 1238, 'end': 1250, 'mesh': 'D009568'}, {'text': 'albuminuria', 'type': 'Disease', 'start': 1265, 'end': 1276, 'mesh': 'D000419'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 1372, 'end': 1384, 'mesh': 'D006973'}, {'text': 'glomerulosclerosis', 'type': 'Disease', 'start': 1408, 'end': 1426, 'mesh': 'D005921'}, {'text': 'nitrendipine', 'type': 'Chemical', 'start': 1468, 'end': 1480, 'mesh': 'D009568'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 1513, 'end': 1525, 'mesh': 'D006973'}, {'text': 'nitrendipine', 'type': 'Chemical', 'start': 1619, 'end': 1631, 'mesh': 'D009568'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 1690, 'end': 1699, 'mesh': 'D004656'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 1759, 'end': 1771, 'mesh': 'D006973'}]"
+483,1527456,Treatment of tinnitus by intratympanic instillation of lignocaine (lidocaine) 2 per cent through ventilation tubes.,"Idiopathic subjective tinnitus (IST) is one of the most obscure otological pathologies. This paper presents the results of treating IST by intratympanic instillation of lignocaine (lidocaine) 2 per cent through a grommet, for five weekly courses. Fifty-two patients suffering from intractable tinnitus entered this therapeutic trial, but only nine finished all five courses. In one patient, the tinnitus was almost completely abolished, but in all the nine patients the decompensated tinnitus changed to a compensated one. We suggest this mode of treatment for patients that were previously treated by drugs, acupuncture and biofeedback, with disappointing results. Patients should be warned about the side effects of vertigo and vomiting, which subsides gradually with every new instillation, and that the tinnitus may not disappear but will be alleviated, enabling them to cope more easily with the disease and lead a more normal life.","[{'text': 'tinnitus', 'type': 'Disease', 'start': 13, 'end': 21, 'mesh': 'D014012'}, {'text': 'lignocaine', 'type': 'Chemical', 'start': 55, 'end': 65, 'mesh': 'D008012'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 67, 'end': 76, 'mesh': 'D008012'}, {'text': 'Idiopathic subjective tinnitus', 'type': 'Disease', 'start': 116, 'end': 146, 'mesh': 'D014012'}, {'text': 'IST', 'type': 'Disease', 'start': 148, 'end': 151, 'mesh': 'D014012'}, {'text': 'IST', 'type': 'Disease', 'start': 248, 'end': 251, 'mesh': 'D014012'}, {'text': 'lignocaine', 'type': 'Chemical', 'start': 285, 'end': 295, 'mesh': 'D008012'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 297, 'end': 306, 'mesh': 'D008012'}, {'text': 'tinnitus', 'type': 'Disease', 'start': 409, 'end': 417, 'mesh': 'D014012'}, {'text': 'tinnitus', 'type': 'Disease', 'start': 511, 'end': 519, 'mesh': 'D014012'}, {'text': 'tinnitus', 'type': 'Disease', 'start': 600, 'end': 608, 'mesh': 'D014012'}, {'text': 'vertigo', 'type': 'Disease', 'start': 834, 'end': 841, 'mesh': 'D014717'}, {'text': 'vomiting', 'type': 'Disease', 'start': 846, 'end': 854, 'mesh': 'D014839'}, {'text': 'tinnitus', 'type': 'Disease', 'start': 923, 'end': 931, 'mesh': 'D014012'}]"
+484,220563,Perhexiline maleate and peripheral neuropathy.,"Peripheral neuropathy has been noted as a complication of therapy with perhexiline maleate, a drug widely used in France (and in clinical trials in the United States) for the prophylactic treatment of angina pectoris. In 24 patients with this complication, the marked slowing of motor nerve conduction velocity and the electromyographic changes imply mainly a demyelinating disorder. Improvement was noted with cessation of therapy. In a few cases the presence of active denervation signified a poor prognosis, with only slight improvement. The underlying mechanism causing the neuropathy is not yet fully known, although some evidence indicates that it may be a lipid storage process.","[{'text': 'Perhexiline maleate', 'type': 'Chemical', 'start': 0, 'end': 19, 'mesh': 'C023470'}, {'text': 'peripheral neuropathy', 'type': 'Disease', 'start': 24, 'end': 45, 'mesh': 'D010523'}, {'text': 'Peripheral neuropathy', 'type': 'Disease', 'start': 47, 'end': 68, 'mesh': 'D010523'}, {'text': 'perhexiline maleate', 'type': 'Chemical', 'start': 118, 'end': 137, 'mesh': 'C023470'}, {'text': 'angina pectoris', 'type': 'Disease', 'start': 248, 'end': 263, 'mesh': 'D000787'}, {'text': 'demyelinating disorder', 'type': 'Disease', 'start': 407, 'end': 429, 'mesh': 'D003711'}, {'text': 'neuropathy', 'type': 'Disease', 'start': 625, 'end': 635, 'mesh': 'D009422'}]"
+485,137340,Effect of humoral modulators of morphine-induced increase in locomotor activity of mice.,"The effect of humoral modulators on the morphine-induced increase in locomotor activity of mice was studied. The subcutaneous administration of 10 mg/kg of morphine-HC1 produced a marked increase in locomotor activity in mice. The morphine-induced hyperactivity was potentiated by scopolamine and attenuated by physostigmine. In contrast, both methscopolamine and neostigmine, which do not penetrate the blood-brain barrier, had no effect on the hyperactivity produced by morphine. Pretreatment of mice with alpha-methyltyrosine (20 mg/kg i.p., one hour), an inhibitor of tyrosine hydroxylase, significantly decreased the activity-increasing effects of morphine. On the other hand, pretreatment with p-chlorophenylalamine (3 X 320 mg/kg i.p., 24 hr), a serotonin depletor, caused no significant change in the hyperactivity. The study suggests that the activity-increasing effects of morphine are mediated by the release of catecholamines from adrenergic neurons in the brain. And the results are consistent with the hypothesis that morphine acts by retarding the release of acetylcholine at some central cholinergic synapses. It is also suggested from collected evidence that the activity-increasing effects of morphine in mice are mediated by mechanisms different from those which mediate the activity-increasing effects of morphine in rats.","[{'text': 'morphine', 'type': 'Chemical', 'start': 32, 'end': 40, 'mesh': 'D009020'}, {'text': 'increase in locomotor activity', 'type': 'Disease', 'start': 49, 'end': 79, 'mesh': 'D006948'}, {'text': 'morphine', 'type': 'Chemical', 'start': 129, 'end': 137, 'mesh': 'D009020'}, {'text': 'increase in locomotor activity', 'type': 'Disease', 'start': 146, 'end': 176, 'mesh': 'D006948'}, {'text': 'morphine', 'type': 'Chemical', 'start': 245, 'end': 253, 'mesh': 'D009020'}, {'text': 'increase in locomotor activity', 'type': 'Disease', 'start': 276, 'end': 306, 'mesh': 'D006948'}, {'text': 'morphine', 'type': 'Chemical', 'start': 320, 'end': 328, 'mesh': 'D009020'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 337, 'end': 350, 'mesh': 'D006948'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 370, 'end': 381, 'mesh': 'D012601'}, {'text': 'physostigmine', 'type': 'Chemical', 'start': 400, 'end': 413, 'mesh': 'D010830'}, {'text': 'methscopolamine', 'type': 'Chemical', 'start': 433, 'end': 448, 'mesh': 'D019832'}, {'text': 'neostigmine', 'type': 'Chemical', 'start': 453, 'end': 464, 'mesh': 'D009388'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 535, 'end': 548, 'mesh': 'D006948'}, {'text': 'morphine', 'type': 'Chemical', 'start': 561, 'end': 569, 'mesh': 'D009020'}, {'text': 'alpha-methyltyrosine', 'type': 'Chemical', 'start': 597, 'end': 617, 'mesh': 'D019805'}, {'text': 'tyrosine', 'type': 'Chemical', 'start': 661, 'end': 669, 'mesh': 'D014443'}, {'text': 'morphine', 'type': 'Chemical', 'start': 742, 'end': 750, 'mesh': 'D009020'}, {'text': 'p-chlorophenylalamine', 'type': 'Chemical', 'start': 789, 'end': 810, 'mesh': 'D010134'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 842, 'end': 851, 'mesh': 'D012701'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 898, 'end': 911, 'mesh': 'D006948'}, {'text': 'morphine', 'type': 'Chemical', 'start': 972, 'end': 980, 'mesh': 'D009020'}, {'text': 'catecholamines', 'type': 'Chemical', 'start': 1012, 'end': 1026, 'mesh': 'D002395'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1121, 'end': 1129, 'mesh': 'D009020'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 1163, 'end': 1176, 'mesh': 'D000109'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1300, 'end': 1308, 'mesh': 'D009020'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1414, 'end': 1422, 'mesh': 'D009020'}]"
+486,9931093,Mechanisms of FK 506-induced hypertension in the rat.,"-Tacrolimus (FK 506) is a powerful, widely used immunosuppressant. The clinical utility of FK 506 is complicated by substantial hypertension and nephrotoxicity. To clarify the mechanisms of FK 506-induced hypertension, we studied the chronic effects of FK 506 on the synthesis of endothelin-1 (ET-1), the expression of mRNA of ET-1 and endothelin-converting enzyme-1 (ECE-1), the endothelial nitric oxide synthase (eNOS) activity, and the expression of mRNA of eNOS and C-type natriuretic peptide (CNP) in rat blood vessels. In addition, the effect of the specific endothelin type A receptor antagonist FR 139317 on FK 506-induced hypertension in rats was studied. FK 506, 5 mg. kg-1. d-1 given for 4 weeks, elevated blood pressure from 102+/-13 to 152+/-15 mm Hg and increased the synthesis of ET-1 and the levels of ET-1 mRNA in the mesenteric artery (240% and 230%, respectively). Little change was observed in the expression of ECE-1 mRNA and CNP mRNA. FK 506 decreased eNOS activity and the levels of eNOS mRNA in the aorta (48% and 55%, respectively). The administration of FR 139317 (10 mg. kg-1. d-1) prevented FK 506-induced hypertension in rats. These results indicate that FK 506 may increase blood pressure not only by increasing ET-1 production but also by decreasing NO synthesis in the vasculature.","[{'text': 'FK 506', 'type': 'Chemical', 'start': 14, 'end': 20, 'mesh': 'D016559'}, {'text': 'hypertension', 'type': 'Disease', 'start': 29, 'end': 41, 'mesh': 'D006973'}, {'text': 'Tacrolimus', 'type': 'Chemical', 'start': 55, 'end': 65, 'mesh': 'D016559'}, {'text': 'FK 506', 'type': 'Chemical', 'start': 67, 'end': 73, 'mesh': 'D016559'}, {'text': 'FK 506', 'type': 'Chemical', 'start': 145, 'end': 151, 'mesh': 'D016559'}, {'text': 'hypertension', 'type': 'Disease', 'start': 182, 'end': 194, 'mesh': 'D006973'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 199, 'end': 213, 'mesh': 'D007674'}, {'text': 'FK 506', 'type': 'Chemical', 'start': 244, 'end': 250, 'mesh': 'D016559'}, {'text': 'hypertension', 'type': 'Disease', 'start': 259, 'end': 271, 'mesh': 'D006973'}, {'text': 'FK 506', 'type': 'Chemical', 'start': 307, 'end': 313, 'mesh': 'D016559'}, {'text': 'nitric oxide', 'type': 'Chemical', 'start': 446, 'end': 458, 'mesh': 'D009569'}, {'text': 'FR 139317', 'type': 'Chemical', 'start': 657, 'end': 666, 'mesh': 'C079574'}, {'text': 'FK 506', 'type': 'Chemical', 'start': 670, 'end': 676, 'mesh': 'D016559'}, {'text': 'hypertension', 'type': 'Disease', 'start': 685, 'end': 697, 'mesh': 'D006973'}, {'text': 'FK 506', 'type': 'Chemical', 'start': 719, 'end': 725, 'mesh': 'D016559'}, {'text': 'FK 506', 'type': 'Chemical', 'start': 1011, 'end': 1017, 'mesh': 'D016559'}, {'text': 'FR 139317', 'type': 'Chemical', 'start': 1134, 'end': 1143, 'mesh': 'C079574'}, {'text': 'FK 506', 'type': 'Chemical', 'start': 1173, 'end': 1179, 'mesh': 'D016559'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1188, 'end': 1200, 'mesh': 'D006973'}, {'text': 'FK 506', 'type': 'Chemical', 'start': 1238, 'end': 1244, 'mesh': 'D016559'}, {'text': 'NO', 'type': 'Chemical', 'start': 1335, 'end': 1337, 'mesh': 'D009569'}]"
+487,20633755,Suxamethonium induced prolonged apnea in a patient receiving electroconvulsive therapy.,"Suxamethonium causes prolonged apnea in patients in whom pseudocholinesterase enzyme gets deactivated by organophosphorus (OP) poisons. Here, we present a similar incident in a severely depressed patient who received electroconvulsive therapy (ECT). Prolonged apnea in our case ensued because the information about suicidal attempt by OP compound was concealed from the treating team.","[{'text': 'Suxamethonium', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'D013390'}, {'text': 'apnea', 'type': 'Disease', 'start': 32, 'end': 37, 'mesh': 'D001049'}, {'text': 'Suxamethonium', 'type': 'Chemical', 'start': 88, 'end': 101, 'mesh': 'D013390'}, {'text': 'apnea', 'type': 'Disease', 'start': 119, 'end': 124, 'mesh': 'D001049'}, {'text': 'organophosphorus (OP) poisons', 'type': 'Chemical', 'start': 193, 'end': 222, 'mesh': 'D009943'}, {'text': 'depressed', 'type': 'Disease', 'start': 274, 'end': 283, 'mesh': 'D003866'}, {'text': 'apnea', 'type': 'Disease', 'start': 348, 'end': 353, 'mesh': 'D001049'}, {'text': 'OP compound', 'type': 'Chemical', 'start': 423, 'end': 434, 'mesh': 'D009943'}]"
+488,20067456,The effects of the adjunctive bupropion on male sexual dysfunction induced by a selective serotonin reuptake inhibitor: a double-blind placebo-controlled and randomized study.,"OBJECTIVE: To determine the safety and efficacy of adjunctive bupropion sustained-release (SR) on male sexual dysfunction (SD) induced by a selective serotonin reuptake inhibitor (SSRI), as SD is a common side-effect of SSRIs and the most effective treatments have yet to be determined. PATIENTS AND METHODS: The randomized sample consisted of 234 euthymic men who were receiving some type of SSRI. The men were randomly assigned to bupropion SR (150 mg twice daily, 117) or placebo (twice daily, 117) for 12 weeks. Efficacy was evaluated using the Clinical Global Impression-Sexual Function (CGI-SF; the primary outcome measure), the International Index of Erectile Function (IIEF), Arizona Sexual Experience Scale (ASEX), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) (secondary outcome measures). Participants were followed biweekly during study period. RESULTS: After 12 weeks of treatment, the mean (sd) scores for CGI-SF were significantly lower, i.e. better, in patients on bupropion SR, at 2.4 (1.2), than in the placebo group, at 3.9 (1.1) (P= 0.01). Men who received bupropion had a significant increase in the total IIEF score (54.4% vs 1.2%; P= 0.003), and in the five different domains of the IIEF. Total ASEX scores were significantly lower, i.e. better, among men who received bupropion than placebo, at 15.5 (4.3) vs 21.5 (4.7) (P= 0.002). The EDITS scores were 67.4 (10.2) for the bupropion and 36.3 (11.7) for the placebo group (P= 0.001). The ASEX score and CGI-SF score were correlated (P= 0.003). In linear regression analyses the CGI-SF score was not affected significantly by the duration of SD, type of SSRI used and age. CONCLUSIONS: Bupropion is an effective treatment for male SD induced by SSRIs. These results provide empirical support for conducting a further study of bupropion.","[{'text': 'bupropion', 'type': 'Chemical', 'start': 30, 'end': 39, 'mesh': 'D016642'}, {'text': 'sexual dysfunction', 'type': 'Disease', 'start': 48, 'end': 66, 'mesh': 'D012735'}, {'text': 'selective serotonin reuptake inhibitor', 'type': 'Chemical', 'start': 80, 'end': 118, 'mesh': 'D017367'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 238, 'end': 247, 'mesh': 'D016642'}, {'text': 'sexual dysfunction', 'type': 'Disease', 'start': 279, 'end': 297, 'mesh': 'D012735'}, {'text': 'SD', 'type': 'Disease', 'start': 299, 'end': 301, 'mesh': 'D012735'}, {'text': 'selective serotonin reuptake inhibitor', 'type': 'Chemical', 'start': 316, 'end': 354, 'mesh': 'D017367'}, {'text': 'SSRI', 'type': 'Chemical', 'start': 356, 'end': 360, 'mesh': 'D017367'}, {'text': 'SD', 'type': 'Disease', 'start': 366, 'end': 368, 'mesh': 'D012735'}, {'text': 'SSRIs', 'type': 'Chemical', 'start': 396, 'end': 401, 'mesh': 'D017367'}, {'text': 'SSRI', 'type': 'Chemical', 'start': 569, 'end': 573, 'mesh': 'D017367'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 609, 'end': 618, 'mesh': 'D016642'}, {'text': 'Erectile Dysfunction', 'type': 'Disease', 'start': 904, 'end': 924, 'mesh': 'D007172'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 1180, 'end': 1189, 'mesh': 'D016642'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 1276, 'end': 1285, 'mesh': 'D016642'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 1491, 'end': 1500, 'mesh': 'D016642'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 1597, 'end': 1606, 'mesh': 'D016642'}, {'text': 'SD', 'type': 'Disease', 'start': 1814, 'end': 1816, 'mesh': 'D012735'}, {'text': 'SSRI', 'type': 'Chemical', 'start': 1826, 'end': 1830, 'mesh': 'D017367'}, {'text': 'Bupropion', 'type': 'Chemical', 'start': 1858, 'end': 1867, 'mesh': 'D016642'}, {'text': 'SD', 'type': 'Disease', 'start': 1903, 'end': 1905, 'mesh': 'D012735'}, {'text': 'SSRIs', 'type': 'Chemical', 'start': 1917, 'end': 1922, 'mesh': 'D017367'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 1998, 'end': 2007, 'mesh': 'D016642'}]"
+489,18464113,Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis-B surface antigen (HBSAG) seropositive cancer patients undergoing cytotoxic chemotherapy.,"Hepatitis B virus (HBV) is one of the major causes of chronic liver disease worldwide. Cancer patients who are chronic carriers of HBV have a higher hepatic complication rate while receiving cytotoxic chemotherapy (CT) and this has mainly been attributed to HBV reactivation. In this study, cancer patients who have solid and hematological malignancies with chronic HBV infection received the antiviral agent lamivudine prior and during CT compared with historical control group who did not receive lamivudine. The objectives were to assess the efficacy of lamivudine in reducing the incidence of HBV reactivation, and diminishing morbidity and mortality during CT. Two groups were compared in this study. The prophylactic lamivudin group consisted of 37 patients who received prophylactic lamivudine treatment. The historical controls consisted of 50 consecutive patients who underwent CT without prophylactic lamivudine. They were followed up during and for 8 weeks after CT. The outcomes were compared for both groups. Of our control group (n= 50), 21 patients (42%) were established hepatitis. Twelve (24%) of them were evaluated as severe hepatitis. In the prophylactic lamivudine group severe hepatitis were observed only in 1 patient (2.7%) of 37 patients (p < 0.006). Comparison of the mean ALT values revealed significantly higher mean alanine aminotransferase (ALT) values in the control group than the prophylactic lamivudine group; 154:64 (p < 0.32). Our study suggests that prophylactic lamivudine significantly decreases the incidence of HBV reactivation and overall morbidity in cancer patients during and after immunosuppressive therapy. Further studies are needed to determine the most appropriate nucleoside or nucleotide analogue for antiviral prophylaxis during CT and the optimal duration of administration after completion of CT.","[{'text': 'Lamivudine', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D019259'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 33, 'end': 44, 'mesh': 'D006509'}, {'text': 'hepatitis-B surface antigen', 'type': 'Chemical', 'start': 67, 'end': 94, 'mesh': 'D006514'}, {'text': 'HBSAG', 'type': 'Chemical', 'start': 96, 'end': 101, 'mesh': 'D006514'}, {'text': 'cancer', 'type': 'Disease', 'start': 116, 'end': 122, 'mesh': 'D009369'}, {'text': 'Hepatitis B', 'type': 'Disease', 'start': 167, 'end': 178, 'mesh': 'D006509'}, {'text': 'liver disease', 'type': 'Disease', 'start': 229, 'end': 242, 'mesh': 'D008107'}, {'text': 'Cancer', 'type': 'Disease', 'start': 254, 'end': 260, 'mesh': 'D009369'}, {'text': 'hepatic complication', 'type': 'Disease', 'start': 316, 'end': 336, 'mesh': 'D008107'}, {'text': 'cancer', 'type': 'Disease', 'start': 458, 'end': 464, 'mesh': 'D009369'}, {'text': 'hematological malignancies', 'type': 'Disease', 'start': 493, 'end': 519, 'mesh': 'D019337'}, {'text': 'HBV infection', 'type': 'Disease', 'start': 533, 'end': 546, 'mesh': 'D006509'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 576, 'end': 586, 'mesh': 'D019259'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 666, 'end': 676, 'mesh': 'D019259'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 724, 'end': 734, 'mesh': 'D019259'}, {'text': 'lamivudin', 'type': 'Chemical', 'start': 890, 'end': 899, 'mesh': 'D019259'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 957, 'end': 967, 'mesh': 'D019259'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 1078, 'end': 1088, 'mesh': 'D019259'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 1254, 'end': 1263, 'mesh': 'D056486'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 1311, 'end': 1320, 'mesh': 'D056486'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 1342, 'end': 1352, 'mesh': 'D019259'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 1366, 'end': 1375, 'mesh': 'D056486'}, {'text': 'alanine', 'type': 'Chemical', 'start': 1512, 'end': 1519, 'mesh': 'D000409'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 1593, 'end': 1603, 'mesh': 'D019259'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 1667, 'end': 1677, 'mesh': 'D019259'}, {'text': 'cancer', 'type': 'Disease', 'start': 1761, 'end': 1767, 'mesh': 'D009369'}, {'text': 'nucleoside', 'type': 'Chemical', 'start': 1882, 'end': 1892, 'mesh': 'D009705'}, {'text': 'nucleotide', 'type': 'Chemical', 'start': 1896, 'end': 1906, 'mesh': 'D009711'}]"
+490,18308784,Ginsenoside Rg1 restores the impairment of learning induced by chronic morphine administration in rats.,"Rg1, as a ginsenoside extracted from Panax ginseng, could ameliorate spatial learning impairment. Previous studies have demonstrated that Rg1 might be a useful agent for the prevention and treatment of the adverse effects of morphine. The aim of this study was to investigate the effect of Rg1 on learning impairment by chronic morphine administration and the mechanism responsible for this effect. Male rats were subcutaneously injected with morphine (10 mg/kg) twice a day at 12 hour intervals for 10 days, and Rg1 (30 mg/kg) was intraperitoneally injected 2 hours after the second injection of morphine once a day for 10 days. Spatial learning capacity was assessed in the Morris water maze. The results showed that rats treated with Morphine/Rg1 decreased escape latency and increased the time spent in platform quadrant and entering frequency. By implantation of electrodes and electrophysiological recording in vivo, the results showed that Rg1 restored the long-term potentiation (LTP) impaired by morphine in both freely moving and anaesthetised rats. The electrophysiological recording in vitro showed that Rg1 restored the LTP in slices from the rats treated with morphine, but not changed LTP in the slices from normal saline- or morphine/Rg1-treated rats; this restoration could be inhibited by N-methyl-D-aspartate (NMDA) receptor antagonist MK801. We conclude that Rg1 may significantly improve the spatial learning capacity impaired by chonic morphine administration and restore the morphine-inhibited LTP. This effect is NMDA receptor dependent.","[{'text': 'Ginsenoside Rg1', 'type': 'Chemical', 'start': 0, 'end': 15, 'mesh': 'C035054'}, {'text': 'impairment of learning', 'type': 'Disease', 'start': 29, 'end': 51, 'mesh': 'D007859'}, {'text': 'morphine', 'type': 'Chemical', 'start': 71, 'end': 79, 'mesh': 'D009020'}, {'text': 'Rg1', 'type': 'Chemical', 'start': 104, 'end': 107, 'mesh': 'C035054'}, {'text': 'ginsenoside', 'type': 'Chemical', 'start': 114, 'end': 125, 'mesh': 'D036145'}, {'text': 'learning impairment', 'type': 'Disease', 'start': 181, 'end': 200, 'mesh': 'D007859'}, {'text': 'Rg1', 'type': 'Chemical', 'start': 242, 'end': 245, 'mesh': 'C035054'}, {'text': 'morphine', 'type': 'Chemical', 'start': 329, 'end': 337, 'mesh': 'D009020'}, {'text': 'Rg1', 'type': 'Chemical', 'start': 394, 'end': 397, 'mesh': 'C035054'}, {'text': 'learning impairment', 'type': 'Disease', 'start': 401, 'end': 420, 'mesh': 'D007859'}, {'text': 'morphine', 'type': 'Chemical', 'start': 432, 'end': 440, 'mesh': 'D009020'}, {'text': 'morphine', 'type': 'Chemical', 'start': 547, 'end': 555, 'mesh': 'D009020'}, {'text': 'Rg1', 'type': 'Chemical', 'start': 617, 'end': 620, 'mesh': 'C035054'}, {'text': 'morphine', 'type': 'Chemical', 'start': 701, 'end': 709, 'mesh': 'D009020'}, {'text': 'Morphine', 'type': 'Chemical', 'start': 841, 'end': 849, 'mesh': 'D009020'}, {'text': 'Rg1', 'type': 'Chemical', 'start': 850, 'end': 853, 'mesh': 'C035054'}, {'text': 'Rg1', 'type': 'Chemical', 'start': 1051, 'end': 1054, 'mesh': 'C035054'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1109, 'end': 1117, 'mesh': 'D009020'}, {'text': 'Rg1', 'type': 'Chemical', 'start': 1220, 'end': 1223, 'mesh': 'C035054'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1278, 'end': 1286, 'mesh': 'D009020'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1345, 'end': 1353, 'mesh': 'D009020'}, {'text': 'Rg1', 'type': 'Chemical', 'start': 1354, 'end': 1357, 'mesh': 'C035054'}, {'text': 'N-methyl-D-aspartate', 'type': 'Chemical', 'start': 1411, 'end': 1431, 'mesh': 'D016202'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 1433, 'end': 1437, 'mesh': 'D016202'}, {'text': 'MK801', 'type': 'Chemical', 'start': 1459, 'end': 1464, 'mesh': 'D016291'}, {'text': 'Rg1', 'type': 'Chemical', 'start': 1483, 'end': 1486, 'mesh': 'C035054'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1562, 'end': 1570, 'mesh': 'D009020'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1602, 'end': 1610, 'mesh': 'D009020'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 1641, 'end': 1645, 'mesh': 'D016202'}]"
+491,17931375,A study on the effect of the duration of subcutaneous heparin injection on bruising and pain.,"AIM: This study was carried out to determine the effect of injection duration on bruising and pain following the administration of the subcutaneous injection of heparin. BACKGROUND: Although different methods to prevent bruising and pain following the subcutaneous injection of heparin have been widely studied and described, the effect of injection duration on the occurrence of bruising and pain is little documented. DESIGN: This study was designed as within-subject, quasi-experimental research. METHOD: The sample for the study consisted of 50 patients to whom subcutaneous heparin was administered. Heparin was injected over 10 seconds on the right abdominal site and 30 seconds on the left abdominal site. Injections areas were assessed for the presence of bruising at 48 and 72 hours after each injection. Dimensions of the bruising on the heparin applied areas were measured using transparent millimetric measuring paper. The visual analog scale (VAS) was used to measure pain intensity and a stop-watch was used to time the pain period. Data were analysed using chi-square test, Mann-Whitney U, Wilcoxon signed ranks tests and correlation. RESULTS: The percentage of bruising occurrence was 64% with the injection of 10 seconds duration and 42% in the 30-second injection. It was determined that the size of the bruising was smaller in the 30-second injection. Pain intensity and pain period were statistically significantly lower for the 30-second injection than for the 10-second injection. CONCLUSIONS: It was determined that injection duration had an effect on bruising and pain following the subcutaneous administration of heparin. This study should be repeated on a larger sample. RELEVANCE TO CLINICAL PRACTICE: When administering subcutaneous heparin injections, it is important to extend the duration of the injection.","[{'text': 'heparin', 'type': 'Chemical', 'start': 54, 'end': 61, 'mesh': 'D006493'}, {'text': 'bruising', 'type': 'Disease', 'start': 75, 'end': 83, 'mesh': 'D003288'}, {'text': 'pain', 'type': 'Disease', 'start': 88, 'end': 92, 'mesh': 'D010146'}, {'text': 'bruising', 'type': 'Disease', 'start': 175, 'end': 183, 'mesh': 'D003288'}, {'text': 'pain', 'type': 'Disease', 'start': 188, 'end': 192, 'mesh': 'D010146'}, {'text': 'heparin', 'type': 'Chemical', 'start': 255, 'end': 262, 'mesh': 'D006493'}, {'text': 'bruising', 'type': 'Disease', 'start': 314, 'end': 322, 'mesh': 'D003288'}, {'text': 'pain', 'type': 'Disease', 'start': 327, 'end': 331, 'mesh': 'D010146'}, {'text': 'heparin', 'type': 'Chemical', 'start': 372, 'end': 379, 'mesh': 'D006493'}, {'text': 'bruising', 'type': 'Disease', 'start': 474, 'end': 482, 'mesh': 'D003288'}, {'text': 'pain', 'type': 'Disease', 'start': 487, 'end': 491, 'mesh': 'D010146'}, {'text': 'heparin', 'type': 'Chemical', 'start': 673, 'end': 680, 'mesh': 'D006493'}, {'text': 'Heparin', 'type': 'Chemical', 'start': 699, 'end': 706, 'mesh': 'D006493'}, {'text': 'bruising', 'type': 'Disease', 'start': 858, 'end': 866, 'mesh': 'D003288'}, {'text': 'bruising', 'type': 'Disease', 'start': 926, 'end': 934, 'mesh': 'D003288'}, {'text': 'heparin', 'type': 'Chemical', 'start': 942, 'end': 949, 'mesh': 'D006493'}, {'text': 'pain', 'type': 'Disease', 'start': 1075, 'end': 1079, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 1128, 'end': 1132, 'mesh': 'D010146'}, {'text': 'bruising', 'type': 'Disease', 'start': 1271, 'end': 1279, 'mesh': 'D003288'}, {'text': 'bruising', 'type': 'Disease', 'start': 1416, 'end': 1424, 'mesh': 'D003288'}, {'text': 'Pain', 'type': 'Disease', 'start': 1465, 'end': 1469, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 1484, 'end': 1488, 'mesh': 'D010146'}, {'text': 'bruising', 'type': 'Disease', 'start': 1669, 'end': 1677, 'mesh': 'D003288'}, {'text': 'pain', 'type': 'Disease', 'start': 1682, 'end': 1686, 'mesh': 'D010146'}, {'text': 'heparin', 'type': 'Chemical', 'start': 1732, 'end': 1739, 'mesh': 'D006493'}, {'text': 'heparin', 'type': 'Chemical', 'start': 1855, 'end': 1862, 'mesh': 'D006493'}]"
+492,15649445,Acute reserpine and subchronic haloperidol treatments change synaptosomal brain glutamate uptake and elicit orofacial dyskinesia in rats.,"Reserpine- and haloperidol-induced orofacial dyskinesia are putative animal models of tardive dyskinesia (TD) whose pathophysiology has been related to free radical generation and oxidative stress. In the present study, the authors induced orofacial dyskinesia by acute reserpine and subchronic haloperidol administration to rats. Reserpine injection (one dose of 1 mg/kg s.c.) every other day for 3 days caused a significant increase in vacuous chewing, tongue protrusion and duration of facial twitching, compared to the control. Haloperidol administration (one dose of 12 mg/kg once a week s.c.) for 4 weeks caused an increase in vacuous chewing, tongue protrusion and duration of facial twitching observed in four weekly evaluations. After the treatments and behavioral observation, glutamate uptake by segments of the brain was analyzed. A decreased glutamate uptake was observed in the subcortical parts of animals treated with reserpine and haloperidol, compared to the control. Importantly, a decrease in glutamate uptake correlates negatively with an increase in the incidence of orofacial diskinesia. These results indicate that early changes in glutamate transport may be related to the development of vacuous chewing movements in rats.","[{'text': 'reserpine', 'type': 'Chemical', 'start': 6, 'end': 15, 'mesh': 'D012110'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 31, 'end': 42, 'mesh': 'D006220'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 80, 'end': 89, 'mesh': 'D018698'}, {'text': 'orofacial dyskinesia', 'type': 'Disease', 'start': 108, 'end': 128, 'mesh': 'D004409'}, {'text': 'Reserpine', 'type': 'Chemical', 'start': 138, 'end': 147, 'mesh': 'D012110'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 153, 'end': 164, 'mesh': 'D006220'}, {'text': 'orofacial dyskinesia', 'type': 'Disease', 'start': 173, 'end': 193, 'mesh': 'D004409'}, {'text': 'tardive dyskinesia', 'type': 'Disease', 'start': 224, 'end': 242, 'mesh': 'D004409'}, {'text': 'TD', 'type': 'Disease', 'start': 244, 'end': 246, 'mesh': 'D004409'}, {'text': 'orofacial dyskinesia', 'type': 'Disease', 'start': 378, 'end': 398, 'mesh': 'D004409'}, {'text': 'reserpine', 'type': 'Chemical', 'start': 408, 'end': 417, 'mesh': 'D012110'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 433, 'end': 444, 'mesh': 'D006220'}, {'text': 'Reserpine', 'type': 'Chemical', 'start': 469, 'end': 478, 'mesh': 'D012110'}, {'text': 'Haloperidol', 'type': 'Chemical', 'start': 670, 'end': 681, 'mesh': 'D006220'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 925, 'end': 934, 'mesh': 'D018698'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 993, 'end': 1002, 'mesh': 'D018698'}, {'text': 'reserpine', 'type': 'Chemical', 'start': 1072, 'end': 1081, 'mesh': 'D012110'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1086, 'end': 1097, 'mesh': 'D006220'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 1151, 'end': 1160, 'mesh': 'D018698'}, {'text': 'orofacial diskinesia', 'type': 'Disease', 'start': 1227, 'end': 1247, 'mesh': 'D004409'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 1294, 'end': 1303, 'mesh': 'D018698'}]"
+493,14698717,Acute psychosis due to treatment with phenytoin in a nonepileptic patient.,"The development of psychosis related to antiepileptic drug treatment is usually attributed to the interaction between the epileptic brain substratum and the antiepileptic drugs. The case of a nonepileptic patient who developed psychosis following phenytoin treatment for trigeminal neuralgia is described. This case suggests that the psychotic symptoms that occur following phenytoin treatment in some epileptic patients may be the direct result of medication, unrelated to seizures.","[{'text': 'Acute psychosis', 'type': 'Disease', 'start': 0, 'end': 15, 'mesh': 'D011605'}, {'text': 'phenytoin', 'type': 'Chemical', 'start': 38, 'end': 47, 'mesh': 'D010672'}, {'text': 'psychosis', 'type': 'Disease', 'start': 94, 'end': 103, 'mesh': 'D011605'}, {'text': 'epileptic', 'type': 'Disease', 'start': 197, 'end': 206, 'mesh': 'D004827'}, {'text': 'psychosis', 'type': 'Disease', 'start': 302, 'end': 311, 'mesh': 'D011605'}, {'text': 'phenytoin', 'type': 'Chemical', 'start': 322, 'end': 331, 'mesh': 'D010672'}, {'text': 'trigeminal neuralgia', 'type': 'Disease', 'start': 346, 'end': 366, 'mesh': 'D014277'}, {'text': 'psychotic symptoms', 'type': 'Disease', 'start': 409, 'end': 427, 'mesh': 'D011605'}, {'text': 'phenytoin', 'type': 'Chemical', 'start': 449, 'end': 458, 'mesh': 'D010672'}, {'text': 'epileptic', 'type': 'Disease', 'start': 477, 'end': 486, 'mesh': 'D004827'}, {'text': 'seizures', 'type': 'Disease', 'start': 549, 'end': 557, 'mesh': 'D012640'}]"
+494,12617329,The effect of treatment with gum Arabic on gentamicin nephrotoxicity in rats: a preliminary study.,"In the present work we assessed the effect of treatment of rats with gum Arabic on acute renal failure induced by gentamicin (GM) nephrotoxicity. Rats were treated with the vehicle (2 mL/kg of distilled water and 5% w/v cellulose, 10 days), gum Arabic (2 mL/kg of a 10% w/v aqueous suspension of gum Arabic powder, orally for 10 days), or gum Arabic concomitantly with GM (80mg/kg/day intramuscularly, during the last six days of the treatment period). Nephrotoxicity was assessed by measuring the concentrations of creatinine and urea in the plasma and reduced glutathione (GSH) in the kidney cortex, and by light microscopic examination of kidney sections. The results indicated that concomitant treatment with gum Arabic and GM significantly increased creatinine and urea by about 183 and 239%, respectively (compared to 432 and 346%, respectively, in rats treated with cellulose and GM), and decreased that of cortical GSH by 21% (compared to 27% in the cellulose plus GM group) The GM-induced proximal tubular necrosis appeared to be slightly less severe in rats given GM together with gum Arabic than in those given GM and cellulose. It could be inferred that gum Arabic treatment has induced a modest amelioration of some of the histological and biochemical indices of GM nephrotoxicity. Further work is warranted on the effect of the treatments on renal functional aspects in models of chronic renal failure, and on the mechanism(s) involved.","[{'text': 'gum Arabic', 'type': 'Chemical', 'start': 29, 'end': 39, 'mesh': 'D006170'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 43, 'end': 53, 'mesh': 'D005839'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 54, 'end': 68, 'mesh': 'D007674'}, {'text': 'gum Arabic', 'type': 'Chemical', 'start': 168, 'end': 178, 'mesh': 'D006170'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 182, 'end': 201, 'mesh': 'D058186'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 213, 'end': 223, 'mesh': 'D005839'}, {'text': 'GM', 'type': 'Chemical', 'start': 225, 'end': 227, 'mesh': 'D005839'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 229, 'end': 243, 'mesh': 'D007674'}, {'text': 'gum Arabic', 'type': 'Chemical', 'start': 340, 'end': 350, 'mesh': 'D006170'}, {'text': 'gum Arabic', 'type': 'Chemical', 'start': 395, 'end': 405, 'mesh': 'D006170'}, {'text': 'gum Arabic', 'type': 'Chemical', 'start': 438, 'end': 448, 'mesh': 'D006170'}, {'text': 'GM', 'type': 'Chemical', 'start': 468, 'end': 470, 'mesh': 'D005839'}, {'text': 'Nephrotoxicity', 'type': 'Disease', 'start': 552, 'end': 566, 'mesh': 'D007674'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 615, 'end': 625, 'mesh': 'D003404'}, {'text': 'urea', 'type': 'Chemical', 'start': 630, 'end': 634, 'mesh': 'D014508'}, {'text': 'glutathione', 'type': 'Chemical', 'start': 661, 'end': 672, 'mesh': 'D005978'}, {'text': 'GSH', 'type': 'Chemical', 'start': 674, 'end': 677, 'mesh': 'D005978'}, {'text': 'gum Arabic', 'type': 'Chemical', 'start': 812, 'end': 822, 'mesh': 'D006170'}, {'text': 'GM', 'type': 'Chemical', 'start': 827, 'end': 829, 'mesh': 'D005839'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 854, 'end': 864, 'mesh': 'D003404'}, {'text': 'urea', 'type': 'Chemical', 'start': 869, 'end': 873, 'mesh': 'D014508'}, {'text': 'GM', 'type': 'Chemical', 'start': 986, 'end': 988, 'mesh': 'D005839'}, {'text': 'GSH', 'type': 'Chemical', 'start': 1022, 'end': 1025, 'mesh': 'D005978'}, {'text': 'GM', 'type': 'Chemical', 'start': 1072, 'end': 1074, 'mesh': 'D005839'}, {'text': 'GM', 'type': 'Chemical', 'start': 1086, 'end': 1088, 'mesh': 'D005839'}, {'text': 'tubular necrosis', 'type': 'Disease', 'start': 1106, 'end': 1122, 'mesh': 'D007683'}, {'text': 'GM', 'type': 'Chemical', 'start': 1173, 'end': 1175, 'mesh': 'D005839'}, {'text': 'gum Arabic', 'type': 'Chemical', 'start': 1190, 'end': 1200, 'mesh': 'D006170'}, {'text': 'GM', 'type': 'Chemical', 'start': 1221, 'end': 1223, 'mesh': 'D005839'}, {'text': 'gum Arabic', 'type': 'Chemical', 'start': 1265, 'end': 1275, 'mesh': 'D006170'}, {'text': 'GM', 'type': 'Chemical', 'start': 1375, 'end': 1377, 'mesh': 'D005839'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1378, 'end': 1392, 'mesh': 'D007674'}, {'text': 'chronic renal failure', 'type': 'Disease', 'start': 1493, 'end': 1514, 'mesh': 'D007676'}]"
+495,12523465,Visual hallucinations associated with zonisamide.,"Zonisamide is a broad-spectrum antiepileptic drug used to treat various types of seizures. Although visual hallucinations have not been reported as an adverse effect of this agent, we describe three patients who experienced complex visual hallucinations and altered mental status after zonisamide treatment was begun or its dosage increased. All three had been diagnosed earlier with epilepsy, and their electroencephalogram (EEG) findings were abnormal. During monitoring, visual hallucinations did not correlate with EEG readings, nor did video recording capture any of the described events. None of the patients had experienced visual hallucinations before this event. The only recent change in their treatment was the introduction or increased dosage of zonisamide. With either discontinuation or decreased dosage of the drug the symptoms disappeared and did not recur. Further observations and reports will help clarify this adverse effect. Until then, clinicians need to be aware of this possible complication associated with zonisamide.","[{'text': 'Visual hallucinations', 'type': 'Disease', 'start': 0, 'end': 21, 'mesh': 'D006212'}, {'text': 'zonisamide', 'type': 'Chemical', 'start': 38, 'end': 48, 'mesh': 'C022189'}, {'text': 'Zonisamide', 'type': 'Chemical', 'start': 50, 'end': 60, 'mesh': 'C022189'}, {'text': 'seizures', 'type': 'Disease', 'start': 131, 'end': 139, 'mesh': 'D012640'}, {'text': 'visual hallucinations', 'type': 'Disease', 'start': 150, 'end': 171, 'mesh': 'D006212'}, {'text': 'visual hallucinations', 'type': 'Disease', 'start': 282, 'end': 303, 'mesh': 'D006212'}, {'text': 'zonisamide', 'type': 'Chemical', 'start': 336, 'end': 346, 'mesh': 'C022189'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 434, 'end': 442, 'mesh': 'D004827'}, {'text': 'visual hallucinations', 'type': 'Disease', 'start': 524, 'end': 545, 'mesh': 'D006212'}, {'text': 'visual hallucinations', 'type': 'Disease', 'start': 681, 'end': 702, 'mesh': 'D006212'}, {'text': 'zonisamide', 'type': 'Chemical', 'start': 808, 'end': 818, 'mesh': 'C022189'}, {'text': 'zonisamide', 'type': 'Chemical', 'start': 1082, 'end': 1092, 'mesh': 'C022189'}]"
+496,11961407,GLEPP1 receptor tyrosine phosphatase (Ptpro) in rat PAN nephrosis. A marker of acute podocyte injury.,"Glomerular epithelial protein 1 (GLEPP1) is a podocyte receptor membrane protein tyrosine phosphatase located on the apical cell membrane of visceral glomerular epithelial cell and foot processes. This receptor plays a role in regulating the structure and function of podocyte foot process. To better understand the utility of GLEPP1 as a marker of glomerular injury, the amount and distribution of GLEPP1 protein and mRNA were examined by immunohistochemistry, Western blot and RNase protection assay in a model of podocyte injury in the rat. Puromycin aminonucleoside nephrosis was induced by single intraperitoneal injection of puromycin aminonucleoside (PAN, 20 mg/100g BW). Tissues were analyzed at 0, 5, 7, 11, 21, 45, 80 and 126 days after PAN injection so as to include both the acute phase of proteinuria associated with foot process effacement (days 5-11) and the chronic phase of proteinuria associated with glomerulosclerosis (days 45-126). At day 5, GLEPP1 protein and mRNA were reduced from the normal range (265.2 +/- 79.6 x 10(6) moles/glomerulus and 100%) to 15% of normal (41.8 +/- 4.8 x 10(6) moles/glomerulus, p < 0.005). This occurred in association with an increase in urinary protein content from 1.8 +/- 1 to 99.0 +/- 61 mg/day (p < 0.001). In contrast, podocalyxin did not change significantly at this time. By day 11, GLEPP1 protein and mRNA had begun to return towards baseline. By day 45-126, at a time when glomerular scarring was present, GLEPP1 was absent from glomerulosclerotic areas although the total glomerular content of GLEPP1 was not different from normal. We conclude that GLEPP1 expression, unlike podocalyxin, reflects podocyte injury induced by PAN. GLEPP1 expression may be a useful marker of podocyte injury.","[{'text': 'tyrosine', 'type': 'Chemical', 'start': 16, 'end': 24, 'mesh': 'D014443'}, {'text': 'PAN', 'type': 'Chemical', 'start': 52, 'end': 55, 'mesh': 'D011692'}, {'text': 'nephrosis', 'type': 'Disease', 'start': 56, 'end': 65, 'mesh': 'D009401'}, {'text': 'tyrosine', 'type': 'Chemical', 'start': 183, 'end': 191, 'mesh': 'D014443'}, {'text': 'glomerular injury', 'type': 'Disease', 'start': 451, 'end': 468, 'mesh': 'D007674'}, {'text': 'Puromycin aminonucleoside', 'type': 'Chemical', 'start': 646, 'end': 671, 'mesh': 'D011692'}, {'text': 'nephrosis', 'type': 'Disease', 'start': 672, 'end': 681, 'mesh': 'D009401'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 733, 'end': 758, 'mesh': 'D011692'}, {'text': 'PAN', 'type': 'Chemical', 'start': 760, 'end': 763, 'mesh': 'D011692'}, {'text': 'PAN', 'type': 'Chemical', 'start': 849, 'end': 852, 'mesh': 'D011692'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 904, 'end': 915, 'mesh': 'D011507'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 993, 'end': 1004, 'mesh': 'D011507'}, {'text': 'glomerulosclerosis', 'type': 'Disease', 'start': 1021, 'end': 1039, 'mesh': 'D005921'}, {'text': 'PAN', 'type': 'Chemical', 'start': 1790, 'end': 1793, 'mesh': 'D011692'}]"
+497,9401499,Ticlopidine-induced aplastic anemia: report of three Chinese patients and review of the literature.,"In this study, three Chinese patients with ticlopidine-induced aplastic anemia were reported and another 13 patients in the English literature were reviewed. We attempted to find underlying similarities, evaluate the risk factors, and identify appropriate treatment for this complication. All but one of the patients were over 60 years old, and the 6 who died were all older than 65. Therefore, old age may be a risk factor for developing this complication. Agranulocytosis occurred 3-20 weeks after initiation of ticlopidine, so frequent examination of white cell count during treatment is recommended. There seemed to be no direct correlation between the dose or duration used and the severity of bone marrow suppression. Treatment for ticlopidine-induced aplastic anemia with colony-stimulating factors seemed to have little effect. The fact that 5 of the 6 patients who received concurrent calcium channel blockers died, should alert clinicians to be more cautious when using these two drugs simultaneously.","[{'text': 'Ticlopidine', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D013988'}, {'text': 'aplastic anemia', 'type': 'Disease', 'start': 20, 'end': 35, 'mesh': 'D000741'}, {'text': 'ticlopidine', 'type': 'Chemical', 'start': 143, 'end': 154, 'mesh': 'D013988'}, {'text': 'aplastic anemia', 'type': 'Disease', 'start': 163, 'end': 178, 'mesh': 'D000741'}, {'text': 'Agranulocytosis', 'type': 'Disease', 'start': 558, 'end': 573, 'mesh': 'D000380'}, {'text': 'ticlopidine', 'type': 'Chemical', 'start': 614, 'end': 625, 'mesh': 'D013988'}, {'text': 'bone marrow suppression', 'type': 'Disease', 'start': 799, 'end': 822, 'mesh': 'D001855'}, {'text': 'ticlopidine', 'type': 'Chemical', 'start': 838, 'end': 849, 'mesh': 'D013988'}, {'text': 'aplastic anemia', 'type': 'Disease', 'start': 858, 'end': 873, 'mesh': 'D000741'}, {'text': 'calcium', 'type': 'Chemical', 'start': 994, 'end': 1001, 'mesh': 'D002118'}]"
+498,2273650,Facilitation of memory retrieval by pre-test morphine and its state dependency in the step-through type passive avoidance learning test in mice.,"Amnesia produced by scopolamine and cycloheximide were reversed by morphine given 30 min before the test trial (pre-test), and pre-test morphine also facilitated the memory retrieval in the animals administered naloxone during the training trial. Similarly, pre-test scopolamine partially reversed the scopolamine-induced amnesia, but not significantly; and pre-test cycloheximide failed to reverse the cycloheximide-induced amnesia. These results suggest that the facilitation of memory retrieval by pre-test morphine might be the direct action of morphine rather than a state dependent effect.","[{'text': 'morphine', 'type': 'Chemical', 'start': 45, 'end': 53, 'mesh': 'D009020'}, {'text': 'Amnesia', 'type': 'Disease', 'start': 145, 'end': 152, 'mesh': 'D000647'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 165, 'end': 176, 'mesh': 'D012601'}, {'text': 'cycloheximide', 'type': 'Chemical', 'start': 181, 'end': 194, 'mesh': 'D003513'}, {'text': 'morphine', 'type': 'Chemical', 'start': 212, 'end': 220, 'mesh': 'D009020'}, {'text': 'morphine', 'type': 'Chemical', 'start': 281, 'end': 289, 'mesh': 'D009020'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 356, 'end': 364, 'mesh': 'D009270'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 412, 'end': 423, 'mesh': 'D012601'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 447, 'end': 458, 'mesh': 'D012601'}, {'text': 'amnesia', 'type': 'Disease', 'start': 467, 'end': 474, 'mesh': 'D000647'}, {'text': 'cycloheximide', 'type': 'Chemical', 'start': 512, 'end': 525, 'mesh': 'D003513'}, {'text': 'cycloheximide', 'type': 'Chemical', 'start': 548, 'end': 561, 'mesh': 'D003513'}, {'text': 'amnesia', 'type': 'Disease', 'start': 570, 'end': 577, 'mesh': 'D000647'}, {'text': 'morphine', 'type': 'Chemical', 'start': 655, 'end': 663, 'mesh': 'D009020'}, {'text': 'morphine', 'type': 'Chemical', 'start': 694, 'end': 702, 'mesh': 'D009020'}]"
+499,10683478,Test conditions influence the response to a drug challenge in rodents.,"These studies were conducted to examine the differential response to a drug challenge under varied experimental test conditions routinely employed to study drug-induced behavioral and neurophysiological responses in rodents. Apomorphine, a nonselective dopamine agonist, was selected due to its biphasic behavioral effects, its ability to induce hypothermia, and to produce distinct changes to dopamine turnover in the rodent brain. From such experiments there is evidence that characterization and detection of apomorphine-induced activity in rodents critically depends upon the test conditions employed. In rats, detection of apomorphine-induced hyperactivity was facilitated by a period of acclimatization to the test conditions. Moreover, test conditions can impact upon other physiological responses to apomorphine such as drug-induced hypothermia. In mice, apomorphine produced qualitatively different responses under novel conditions when compared to those behaviors elicited in the home test cage. Drug-induced gross activity counts were increased in the novel exploratory box only, while measures of stereotypic behavior were similar in both. By contrast, apomorphine-induced locomotion was more prominent in the novel exploratory box. Dopamine turnover ratios (DOPAC:DA and HVA:DA) were found to be lower in those animals exposed to the exploratory box when compared to their home cage counterparts. However, apomorphine-induced reductions in striatal dopamine turnover were detected in both novel and home cage environments. The implications of these findings are discussed with particular emphasis upon conducting psychopharmacological challenge tests in rodents.","[{'text': 'Apomorphine', 'type': 'Chemical', 'start': 296, 'end': 307, 'mesh': 'D001058'}, {'text': 'dopamine agonist', 'type': 'Chemical', 'start': 324, 'end': 340, 'mesh': 'D018491'}, {'text': 'hypothermia', 'type': 'Disease', 'start': 417, 'end': 428, 'mesh': 'D007035'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 465, 'end': 473, 'mesh': 'D004298'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 583, 'end': 594, 'mesh': 'D001058'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 699, 'end': 710, 'mesh': 'D001058'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 719, 'end': 732, 'mesh': 'D006948'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 879, 'end': 890, 'mesh': 'D001058'}, {'text': 'hypothermia', 'type': 'Disease', 'start': 912, 'end': 923, 'mesh': 'D007035'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 934, 'end': 945, 'mesh': 'D001058'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 1236, 'end': 1247, 'mesh': 'D001058'}, {'text': 'Dopamine', 'type': 'Chemical', 'start': 1316, 'end': 1324, 'mesh': 'D004298'}, {'text': 'DOPAC', 'type': 'Chemical', 'start': 1342, 'end': 1347, 'mesh': 'D015102'}, {'text': 'DA', 'type': 'Chemical', 'start': 1348, 'end': 1350, 'mesh': 'D018491'}, {'text': 'HVA', 'type': 'Chemical', 'start': 1355, 'end': 1358, 'mesh': 'D006719'}, {'text': 'DA', 'type': 'Chemical', 'start': 1359, 'end': 1361, 'mesh': 'D018491'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 1490, 'end': 1501, 'mesh': 'D001058'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1533, 'end': 1541, 'mesh': 'D004298'}]"
+500,6794356,Tricuspid valve regurgitation and lithium carbonate toxicity in a newborn infant.,"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.","[{'text': 'Tricuspid valve regurgitation', 'type': 'Disease', 'start': 0, 'end': 29, 'mesh': 'D014262'}, {'text': 'lithium carbonate', 'type': 'Chemical', 'start': 34, 'end': 51, 'mesh': 'D016651'}, {'text': 'toxicity', 'type': 'Disease', 'start': 52, 'end': 60, 'mesh': 'D064420'}, {'text': 'tricuspid regurgitation', 'type': 'Disease', 'start': 105, 'end': 128, 'mesh': 'D014262'}, {'text': 'atrial flutter', 'type': 'Disease', 'start': 130, 'end': 144, 'mesh': 'D001282'}, {'text': 'congestive heart failure', 'type': 'Disease', 'start': 146, 'end': 170, 'mesh': 'D006333'}, {'text': 'lithium', 'type': 'Chemical', 'start': 189, 'end': 196, 'mesh': 'D008094'}, {'text': 'tricuspid regurgitation', 'type': 'Disease', 'start': 265, 'end': 288, 'mesh': 'D014262'}, {'text': 'atrial flutter', 'type': 'Disease', 'start': 293, 'end': 307, 'mesh': 'D001282'}, {'text': 'cardiac disease', 'type': 'Disease', 'start': 345, 'end': 360, 'mesh': 'D006331'}, {'text': 'lithium', 'type': 'Chemical', 'start': 386, 'end': 393, 'mesh': 'D008094'}, {'text': 'Lithium carbonate', 'type': 'Chemical', 'start': 511, 'end': 528, 'mesh': 'D016651'}, {'text': 'congenital heart disease', 'type': 'Disease', 'start': 576, 'end': 600, 'mesh': 'D006331'}, {'text': 'neurologic depression', 'type': 'Disease', 'start': 651, 'end': 672, 'mesh': 'D003866'}, {'text': 'cyanosis', 'type': 'Disease', 'start': 674, 'end': 682, 'mesh': 'D003490'}, {'text': 'cardiac arrhythmia', 'type': 'Disease', 'start': 688, 'end': 706, 'mesh': 'D001145'}]"
+501,6504332,Phenobarbital-induced dyskinesia in a neurologically-impaired child.,"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.","[{'text': 'Phenobarbital', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'D010634'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 22, 'end': 32, 'mesh': 'D004409'}, {'text': 'neurologically-impaired', 'type': 'Disease', 'start': 38, 'end': 61, 'mesh': 'D009422'}, {'text': 'neurologic impairment', 'type': 'Disease', 'start': 99, 'end': 120, 'mesh': 'D009422'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 133, 'end': 143, 'mesh': 'D004409'}, {'text': 'phenobarbital', 'type': 'Chemical', 'start': 164, 'end': 177, 'mesh': 'D010634'}, {'text': 'seizures', 'type': 'Disease', 'start': 190, 'end': 198, 'mesh': 'D012640'}, {'text': 'movement disorders', 'type': 'Disease', 'start': 216, 'end': 234, 'mesh': 'D009069'}, {'text': 'phenobarbital', 'type': 'Chemical', 'start': 294, 'end': 307, 'mesh': 'D010634'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 313, 'end': 323, 'mesh': 'D004409'}, {'text': 'Phenobarbital', 'type': 'Chemical', 'start': 334, 'end': 347, 'mesh': 'D010634'}, {'text': 'movement disorders', 'type': 'Disease', 'start': 415, 'end': 433, 'mesh': 'D009069'}]"
+502,6436733,Acute changes of blood ammonia may predict short-term adverse effects of valproic acid.,"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.","[{'text': 'ammonia', 'type': 'Chemical', 'start': 23, 'end': 30, 'mesh': 'D000641'}, {'text': 'valproic acid', 'type': 'Chemical', 'start': 73, 'end': 86, 'mesh': 'D014635'}, {'text': 'Valproic acid', 'type': 'Chemical', 'start': 88, 'end': 101, 'mesh': 'D014635'}, {'text': 'VPA', 'type': 'Chemical', 'start': 103, 'end': 106, 'mesh': 'D014635'}, {'text': 'epileptic', 'type': 'Disease', 'start': 124, 'end': 133, 'mesh': 'D004827'}, {'text': 'VPA', 'type': 'Chemical', 'start': 237, 'end': 240, 'mesh': 'D014635'}, {'text': 'Ammonia', 'type': 'Chemical', 'start': 316, 'end': 323, 'mesh': 'D000641'}, {'text': 'NH3', 'type': 'Chemical', 'start': 325, 'end': 328, 'mesh': 'D000641'}, {'text': 'drowsiness', 'type': 'Disease', 'start': 399, 'end': 409, 'mesh': 'D006970'}, {'text': 'VPA', 'type': 'Chemical', 'start': 483, 'end': 486, 'mesh': 'D014635'}, {'text': 'VPA', 'type': 'Chemical', 'start': 543, 'end': 546, 'mesh': 'D014635'}, {'text': 'NH3', 'type': 'Chemical', 'start': 572, 'end': 575, 'mesh': 'D000641'}, {'text': 'VPA', 'type': 'Chemical', 'start': 660, 'end': 663, 'mesh': 'D014635'}]"
+503,6293644,Effects of calcitonin on rat extrapyramidal motor system: behavioral and biochemical data.,"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.","[{'text': 'haloperidol', 'type': 'Chemical', 'start': 322, 'end': 333, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 342, 'end': 351, 'mesh': 'D002375'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 380, 'end': 391, 'mesh': 'D001058'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 400, 'end': 413, 'mesh': 'D006948'}, {'text': 'DA', 'type': 'Chemical', 'start': 515, 'end': 517, 'mesh': 'D004298'}, {'text': 'DOPAC', 'type': 'Chemical', 'start': 522, 'end': 527, 'mesh': 'D015102'}, {'text': 'DA', 'type': 'Chemical', 'start': 680, 'end': 682, 'mesh': 'D004298'}]"
+504,6203632,Development of isoproterenol-induced cardiac hypertrophy.,"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.","[{'text': 'isoproterenol', 'type': 'Chemical', 'start': 15, 'end': 28, 'mesh': 'D007545'}, {'text': 'cardiac hypertrophy', 'type': 'Disease', 'start': 37, 'end': 56, 'mesh': 'D006332'}, {'text': 'cardiac hypertrophy', 'type': 'Disease', 'start': 77, 'end': 96, 'mesh': 'D006332'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 180, 'end': 193, 'mesh': 'D007545'}, {'text': 'ISO', 'type': 'Chemical', 'start': 195, 'end': 198, 'mesh': 'D007545'}, {'text': 'hydroxyproline', 'type': 'Chemical', 'start': 318, 'end': 332, 'mesh': 'D006909'}, {'text': 'hydroxyproline', 'type': 'Chemical', 'start': 626, 'end': 640, 'mesh': 'D006909'}, {'text': 'hypertrophic', 'type': 'Disease', 'start': 812, 'end': 824, 'mesh': 'D006984'}, {'text': 'hypertrophy', 'type': 'Disease', 'start': 1058, 'end': 1069, 'mesh': 'D006984'}, {'text': 'ISO', 'type': 'Chemical', 'start': 1093, 'end': 1096, 'mesh': 'D007545'}, {'text': 'ISO', 'type': 'Chemical', 'start': 1222, 'end': 1225, 'mesh': 'D007545'}, {'text': 'hypertrophic', 'type': 'Disease', 'start': 1241, 'end': 1253, 'mesh': 'D006984'}, {'text': 'hypertrophy', 'type': 'Disease', 'start': 1480, 'end': 1491, 'mesh': 'D006984'}, {'text': 'hyperplasia', 'type': 'Disease', 'start': 1496, 'end': 1507, 'mesh': 'D006965'}]"
+505,3131282,Co-carcinogenic effect of retinyl acetate on forestomach carcinogenesis of male F344 rats induced with butylated hydroxyanisole.,"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.","[{'text': 'carcinogenic', 'type': 'Disease', 'start': 3, 'end': 15, 'mesh': 'D063646'}, {'text': 'retinyl acetate', 'type': 'Chemical', 'start': 26, 'end': 41, 'mesh': 'C009166'}, {'text': 'forestomach carcinogenesis', 'type': 'Disease', 'start': 45, 'end': 71, 'mesh': 'D013274'}, {'text': 'butylated hydroxyanisole', 'type': 'Chemical', 'start': 103, 'end': 127, 'mesh': 'D002083'}, {'text': 'retinyl acetate', 'type': 'Chemical', 'start': 163, 'end': 178, 'mesh': 'C009166'}, {'text': 'RA', 'type': 'Chemical', 'start': 180, 'end': 182, 'mesh': 'C009166'}, {'text': 'butylated hydroxyanisole', 'type': 'Chemical', 'start': 187, 'end': 211, 'mesh': 'D002083'}, {'text': 'BHA', 'type': 'Chemical', 'start': 213, 'end': 216, 'mesh': 'D002083'}, {'text': 'forestomach tumorigenesis', 'type': 'Disease', 'start': 230, 'end': 255, 'mesh': 'D013274'}, {'text': 'BHA', 'type': 'Chemical', 'start': 346, 'end': 349, 'mesh': 'D002083'}, {'text': 'RA', 'type': 'Chemical', 'start': 415, 'end': 417, 'mesh': 'C009166'}, {'text': 'BHA', 'type': 'Chemical', 'start': 483, 'end': 486, 'mesh': 'D002083'}, {'text': 'RA', 'type': 'Chemical', 'start': 612, 'end': 614, 'mesh': 'C009166'}, {'text': 'forestomach tumors', 'type': 'Disease', 'start': 675, 'end': 693, 'mesh': 'D013274'}, {'text': 'squamous cell papilloma', 'type': 'Disease', 'start': 695, 'end': 718, 'mesh': 'D010212'}, {'text': 'carcinoma', 'type': 'Disease', 'start': 723, 'end': 732, 'mesh': 'D002277'}, {'text': 'carcinoma', 'type': 'Disease', 'start': 760, 'end': 769, 'mesh': 'D002277'}, {'text': 'carcinoma', 'type': 'Disease', 'start': 800, 'end': 809, 'mesh': 'D002277'}, {'text': 'RA', 'type': 'Chemical', 'start': 830, 'end': 832, 'mesh': 'C009166'}, {'text': 'BHA', 'type': 'Chemical', 'start': 862, 'end': 865, 'mesh': 'D002083'}, {'text': 'RA', 'type': 'Chemical', 'start': 867, 'end': 869, 'mesh': 'C009166'}, {'text': 'BHA', 'type': 'Chemical', 'start': 990, 'end': 993, 'mesh': 'D002083'}, {'text': 'epithelial hyperplasia', 'type': 'Disease', 'start': 1002, 'end': 1024, 'mesh': 'D017573'}, {'text': 'Tumors', 'type': 'Disease', 'start': 1026, 'end': 1032, 'mesh': 'D009369'}, {'text': 'papillomas', 'type': 'Disease', 'start': 1038, 'end': 1048, 'mesh': 'D010212'}, {'text': 'RA', 'type': 'Chemical', 'start': 1090, 'end': 1092, 'mesh': 'C009166'}, {'text': 'RA', 'type': 'Chemical', 'start': 1125, 'end': 1127, 'mesh': 'C009166'}, {'text': 'RA', 'type': 'Chemical', 'start': 1147, 'end': 1149, 'mesh': 'C009166'}, {'text': 'RA', 'type': 'Chemical', 'start': 1241, 'end': 1243, 'mesh': 'C009166'}, {'text': 'BHA', 'type': 'Chemical', 'start': 1276, 'end': 1279, 'mesh': 'D002083'}, {'text': 'forestomach carcinogenesis', 'type': 'Disease', 'start': 1280, 'end': 1306, 'mesh': 'D013274'}]"
+506,3115150,Ketanserin pretreatment reverses alfentanil-induced muscle rigidity.,"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.","[{'text': 'Ketanserin', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D007650'}, {'text': 'alfentanil', 'type': 'Chemical', 'start': 33, 'end': 43, 'mesh': 'D015760'}, {'text': 'muscle rigidity', 'type': 'Disease', 'start': 52, 'end': 67, 'mesh': 'D009127'}, {'text': 'ketanserin', 'type': 'Chemical', 'start': 96, 'end': 106, 'mesh': 'D007650'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 137, 'end': 146, 'mesh': 'D012701'}, {'text': 'muscle rigidity', 'type': 'Disease', 'start': 197, 'end': 212, 'mesh': 'D009127'}, {'text': 'alfentanil', 'type': 'Chemical', 'start': 272, 'end': 282, 'mesh': 'D015760'}, {'text': 'rigidity', 'type': 'Disease', 'start': 375, 'end': 383, 'mesh': 'D009127'}, {'text': 'ketanserin', 'type': 'Chemical', 'start': 471, 'end': 481, 'mesh': 'D007650'}, {'text': 'alfentanil', 'type': 'Chemical', 'start': 542, 'end': 552, 'mesh': 'D015760'}, {'text': 'Chlordiazepoxide', 'type': 'Chemical', 'start': 646, 'end': 662, 'mesh': 'D002707'}, {'text': 'rigidity', 'type': 'Disease', 'start': 725, 'end': 733, 'mesh': 'D009127'}, {'text': 'alfentanil', 'type': 'Chemical', 'start': 746, 'end': 756, 'mesh': 'D015760'}, {'text': 'rigidity', 'type': 'Disease', 'start': 781, 'end': 789, 'mesh': 'D009127'}, {'text': 'ketanserin', 'type': 'Chemical', 'start': 813, 'end': 823, 'mesh': 'D007650'}, {'text': 'alfentanil', 'type': 'Chemical', 'start': 867, 'end': 877, 'mesh': 'D015760'}, {'text': 'alfentanil', 'type': 'Chemical', 'start': 972, 'end': 982, 'mesh': 'D015760'}, {'text': 'ketanserin', 'type': 'Chemical', 'start': 1009, 'end': 1019, 'mesh': 'D007650'}, {'text': 'alfentanil', 'type': 'Chemical', 'start': 1024, 'end': 1034, 'mesh': 'D015760'}, {'text': 'ketanserin', 'type': 'Chemical', 'start': 1156, 'end': 1166, 'mesh': 'D007650'}, {'text': 'muscle rigidity', 'type': 'Disease', 'start': 1237, 'end': 1252, 'mesh': 'D009127'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 1402, 'end': 1411, 'mesh': 'D012701'}, {'text': 'rigidity', 'type': 'Disease', 'start': 1479, 'end': 1487, 'mesh': 'D009127'}]"
+507,2917114,Glycopyrronium requirements for antagonism of the muscarinic side effects of edrophonium.,"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.","[{'text': 'Glycopyrronium', 'type': 'Chemical', 'start': 0, 'end': 14, 'mesh': 'D006024'}, {'text': 'edrophonium', 'type': 'Chemical', 'start': 77, 'end': 88, 'mesh': 'D004491'}, {'text': 'glycopyrronium', 'type': 'Chemical', 'start': 160, 'end': 174, 'mesh': 'D006024'}, {'text': 'edrophonium', 'type': 'Chemical', 'start': 260, 'end': 271, 'mesh': 'D004491'}, {'text': 'glycopyrronium', 'type': 'Chemical', 'start': 510, 'end': 524, 'mesh': 'D006024'}, {'text': 'edrophonium', 'type': 'Chemical', 'start': 613, 'end': 624, 'mesh': 'D004491'}, {'text': 'edrophonium', 'type': 'Chemical', 'start': 660, 'end': 671, 'mesh': 'D004491'}, {'text': 'bradycardias', 'type': 'Disease', 'start': 680, 'end': 692, 'mesh': 'D001919'}, {'text': 'glycopyrronium', 'type': 'Chemical', 'start': 711, 'end': 725, 'mesh': 'D006024'}]"
+508,2564649,Involvement of locus coeruleus and noradrenergic neurotransmission in fentanyl-induced muscular rigidity in the rat.,"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.","[{'text': 'fentanyl', 'type': 'Chemical', 'start': 70, 'end': 78, 'mesh': 'D005283'}, {'text': 'muscular rigidity', 'type': 'Disease', 'start': 87, 'end': 104, 'mesh': 'D009127'}, {'text': 'muscular rigidity', 'type': 'Disease', 'start': 125, 'end': 142, 'mesh': 'D009127'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 205, 'end': 213, 'mesh': 'D005283'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 456, 'end': 464, 'mesh': 'D007649'}, {'text': 'CO2', 'type': 'Chemical', 'start': 534, 'end': 537, 'mesh': 'D002245'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 569, 'end': 577, 'mesh': 'D005283'}, {'text': 'muscular rigidity', 'type': 'Disease', 'start': 746, 'end': 763, 'mesh': 'D009127'}, {'text': 'prazosin', 'type': 'Chemical', 'start': 938, 'end': 946, 'mesh': 'D011224'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 966, 'end': 974, 'mesh': 'D005283'}, {'text': 'muscular rigidity', 'type': 'Disease', 'start': 1143, 'end': 1160, 'mesh': 'D009127'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 1164, 'end': 1172, 'mesh': 'D005283'}]"
+509,2339463,Cerebral sinus thrombosis as a potential hazard of antifibrinolytic treatment in menorrhagia.,"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.","[{'text': 'Cerebral sinus thrombosis', 'type': 'Disease', 'start': 0, 'end': 25, 'mesh': 'D012851'}, {'text': 'menorrhagia', 'type': 'Disease', 'start': 81, 'end': 92, 'mesh': 'D008595'}, {'text': 'epsilon-aminocaproic acid', 'type': 'Chemical', 'start': 221, 'end': 246, 'mesh': 'D015119'}, {'text': 'menorrhagia', 'type': 'Disease', 'start': 259, 'end': 270, 'mesh': 'D008595'}, {'text': 'menorrhagia', 'type': 'Disease', 'start': 328, 'end': 339, 'mesh': 'D008595'}, {'text': 'blood loss', 'type': 'Disease', 'start': 371, 'end': 381, 'mesh': 'D006473'}, {'text': 'thromboembolic disease', 'type': 'Disease', 'start': 410, 'end': 432, 'mesh': 'D013923'}, {'text': 'epsilon-aminocaproic acid', 'type': 'Chemical', 'start': 473, 'end': 498, 'mesh': 'D015119'}, {'text': 'cerebral sinus thrombosis', 'type': 'Disease', 'start': 500, 'end': 525, 'mesh': 'D012851'}, {'text': 'epsilon-aminocaproic acid', 'type': 'Chemical', 'start': 576, 'end': 601, 'mesh': 'D015119'}]"
+510,1545575,Hemorrhagic cystitis complicating bone marrow transplantation.,"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.","[{'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 135, 'end': 151, 'mesh': 'D003520'}, {'text': 'mesna', 'type': 'Chemical', 'start': 510, 'end': 515, 'mesh': 'D015080'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 561, 'end': 577, 'mesh': 'D003520'}, {'text': 'mesna', 'type': 'Chemical', 'start': 761, 'end': 766, 'mesh': 'D015080'}]"
+511,1286498,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.,"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.","[{'text': 'benzodiazepine', 'type': 'Chemical', 'start': 20, 'end': 34, 'mesh': 'D001569'}, {'text': 'flumazenil', 'type': 'Chemical', 'start': 46, 'end': 56, 'mesh': 'D005442'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 99, 'end': 107, 'mesh': 'D003975'}, {'text': 'Flumazenil', 'type': 'Chemical', 'start': 169, 'end': 179, 'mesh': 'D005442'}, {'text': 'Diazepam', 'type': 'Chemical', 'start': 219, 'end': 227, 'mesh': 'D003975'}, {'text': 'benzodiazepine', 'type': 'Chemical', 'start': 289, 'end': 303, 'mesh': 'D001569'}, {'text': 'flumazenil', 'type': 'Chemical', 'start': 316, 'end': 326, 'mesh': 'D005442'}, {'text': 'Flumazenil', 'type': 'Chemical', 'start': 379, 'end': 389, 'mesh': 'D005442'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 530, 'end': 538, 'mesh': 'D003975'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 570, 'end': 578, 'mesh': 'D005283'}, {'text': 'meperidine', 'type': 'Chemical', 'start': 580, 'end': 590, 'mesh': 'D008614'}, {'text': 'morphine', 'type': 'Chemical', 'start': 595, 'end': 603, 'mesh': 'D009020'}, {'text': 'flumazenil', 'type': 'Chemical', 'start': 794, 'end': 804, 'mesh': 'D005442'}, {'text': 'flumazenil', 'type': 'Chemical', 'start': 866, 'end': 876, 'mesh': 'D005442'}, {'text': 'Flumazenil', 'type': 'Chemical', 'start': 1239, 'end': 1249, 'mesh': 'D005442'}, {'text': 'Flumazenil', 'type': 'Chemical', 'start': 1391, 'end': 1401, 'mesh': 'D005442'}, {'text': 'flumazenil', 'type': 'Chemical', 'start': 1485, 'end': 1495, 'mesh': 'D005442'}, {'text': 'nausea', 'type': 'Disease', 'start': 1652, 'end': 1658, 'mesh': 'D009325'}, {'text': 'vomiting', 'type': 'Disease', 'start': 1663, 'end': 1671, 'mesh': 'D014839'}, {'text': 'flumazenil', 'type': 'Chemical', 'start': 1679, 'end': 1689, 'mesh': 'D005442'}, {'text': 'nausea', 'type': 'Disease', 'start': 1700, 'end': 1706, 'mesh': 'D009325'}, {'text': 'pain', 'type': 'Disease', 'start': 1726, 'end': 1730, 'mesh': 'D010146'}, {'text': 'Flumazenil', 'type': 'Chemical', 'start': 1753, 'end': 1763, 'mesh': 'D005442'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 1814, 'end': 1822, 'mesh': 'D003975'}]"
+512,839274,Hepatic adenomas and focal nodular hyperplasia of the liver in young women on oral contraceptives: case reports.,"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.","[{'text': 'adenomas', 'type': 'Disease', 'start': 8, 'end': 16, 'mesh': 'D000236'}, {'text': 'focal nodular hyperplasia', 'type': 'Disease', 'start': 21, 'end': 46, 'mesh': 'D020518'}, {'text': 'oral contraceptives', 'type': 'Chemical', 'start': 78, 'end': 97, 'mesh': 'D003276'}, {'text': 'adenoma', 'type': 'Disease', 'start': 134, 'end': 141, 'mesh': 'D000236'}, {'text': 'focal nodular hyperplasia', 'type': 'Disease', 'start': 153, 'end': 178, 'mesh': 'D020518'}, {'text': 'oral contraceptives', 'type': 'Chemical', 'start': 217, 'end': 236, 'mesh': 'D003276'}, {'text': 'adenoma', 'type': 'Disease', 'start': 554, 'end': 561, 'mesh': 'D000236'}, {'text': 'focal nodular hyperplasia', 'type': 'Disease', 'start': 566, 'end': 591, 'mesh': 'D020518'}]"
+513,591536,Arterial thromboembolism in patients receiving systemic heparin therapy: a complication associated with heparin-induced thrombocytopenia.,"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.","[{'text': 'thromboembolism', 'type': 'Disease', 'start': 9, 'end': 24, 'mesh': 'D013923'}, {'text': 'heparin', 'type': 'Chemical', 'start': 56, 'end': 63, 'mesh': 'D006493'}, {'text': 'heparin', 'type': 'Chemical', 'start': 104, 'end': 111, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 120, 'end': 136, 'mesh': 'D013921'}, {'text': 'thromboembolism', 'type': 'Disease', 'start': 147, 'end': 162, 'mesh': 'D013923'}, {'text': 'heparin', 'type': 'Chemical', 'start': 204, 'end': 211, 'mesh': 'D006493'}, {'text': 'arterial occlusion', 'type': 'Disease', 'start': 253, 'end': 271, 'mesh': 'D001157'}, {'text': 'thrombi', 'type': 'Disease', 'start': 291, 'end': 298, 'mesh': 'D013927'}, {'text': 'ischemia', 'type': 'Disease', 'start': 311, 'end': 319, 'mesh': 'D007511'}, {'text': 'heparin', 'type': 'Chemical', 'start': 374, 'end': 381, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 412, 'end': 428, 'mesh': 'D013921'}, {'text': 'ischemic', 'type': 'Disease', 'start': 622, 'end': 630, 'mesh': 'D007511'}, {'text': 'heparin', 'type': 'Chemical', 'start': 783, 'end': 790, 'mesh': 'D006493'}, {'text': 'thromboembolism', 'type': 'Disease', 'start': 832, 'end': 847, 'mesh': 'D013923'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 852, 'end': 868, 'mesh': 'D013921'}, {'text': 'heparin', 'type': 'Chemical', 'start': 872, 'end': 879, 'mesh': 'D006493'}, {'text': 'platelet aggregation', 'type': 'Disease', 'start': 888, 'end': 908, 'mesh': 'D001791'}, {'text': 'heparin', 'type': 'Chemical', 'start': 963, 'end': 970, 'mesh': 'D006493'}, {'text': 'sodium warfarin', 'type': 'Chemical', 'start': 997, 'end': 1012, 'mesh': 'D014859'}]"
+514,20735774,Long-term prognosis for transplant-free survivors of paracetamol-induced acute liver failure.,"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.","[{'text': 'paracetamol', 'type': 'Chemical', 'start': 53, 'end': 64, 'mesh': 'D000082'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 73, 'end': 92, 'mesh': 'D017114'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 153, 'end': 164, 'mesh': 'D000082'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 173, 'end': 192, 'mesh': 'D017114'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 234, 'end': 245, 'mesh': 'D000082'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 254, 'end': 273, 'mesh': 'D017114'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 362, 'end': 373, 'mesh': 'D000082'}, {'text': 'acute liver injury', 'type': 'Disease', 'start': 382, 'end': 400, 'mesh': 'D056486'}, {'text': 'liver injury', 'type': 'Disease', 'start': 577, 'end': 589, 'mesh': 'D056486'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 600, 'end': 619, 'mesh': 'D017114'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 774, 'end': 785, 'mesh': 'D000082'}, {'text': 'liver injury', 'type': 'Disease', 'start': 794, 'end': 806, 'mesh': 'D056486'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 821, 'end': 840, 'mesh': 'D017114'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 958, 'end': 977, 'mesh': 'D017114'}, {'text': 'liver disease', 'type': 'Disease', 'start': 986, 'end': 999, 'mesh': 'D008107'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 1102, 'end': 1121, 'mesh': 'D017114'}, {'text': 'substance abuse', 'type': 'Disease', 'start': 1236, 'end': 1251, 'mesh': 'D019966'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 1271, 'end': 1290, 'mesh': 'D017114'}, {'text': 'Paracetamol', 'type': 'Chemical', 'start': 1305, 'end': 1316, 'mesh': 'D000082'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 1325, 'end': 1344, 'mesh': 'D017114'}, {'text': 'liver failure', 'type': 'Disease', 'start': 1437, 'end': 1450, 'mesh': 'D017093'}, {'text': 'liver failure', 'type': 'Disease', 'start': 1467, 'end': 1480, 'mesh': 'D017093'}]"
+515,20705401,Serotonin 6 receptor gene is associated with methamphetamine-induced psychosis in a Japanese population.,"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.","[{'text': 'Serotonin', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D012701'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 45, 'end': 60, 'mesh': 'D008694'}, {'text': 'psychosis', 'type': 'Disease', 'start': 69, 'end': 78, 'mesh': 'D011605'}, {'text': 'psychotic disorders', 'type': 'Disease', 'start': 208, 'end': 227, 'mesh': 'D011605'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 236, 'end': 249, 'mesh': 'D012559'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 255, 'end': 264, 'mesh': 'D012701'}, {'text': '5-HT', 'type': 'Chemical', 'start': 268, 'end': 272, 'mesh': 'D012701'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 365, 'end': 374, 'mesh': 'D003024'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 379, 'end': 389, 'mesh': 'C076029'}, {'text': 'd-amphetamine', 'type': 'Chemical', 'start': 395, 'end': 408, 'mesh': 'D003913'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 417, 'end': 430, 'mesh': 'D006948'}, {'text': '5-HT', 'type': 'Chemical', 'start': 480, 'end': 484, 'mesh': 'D012701'}, {'text': 'd-amphetamine', 'type': 'Chemical', 'start': 565, 'end': 578, 'mesh': 'D003913'}, {'text': 'phencyclidine', 'type': 'Chemical', 'start': 582, 'end': 595, 'mesh': 'D010622'}, {'text': '5-HT', 'type': 'Chemical', 'start': 612, 'end': 616, 'mesh': 'D012701'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 741, 'end': 754, 'mesh': 'D012559'}, {'text': '5-HT', 'type': 'Chemical', 'start': 801, 'end': 805, 'mesh': 'D012701'}, {'text': 'psychotic disorders', 'type': 'Disease', 'start': 856, 'end': 875, 'mesh': 'D011605'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 893, 'end': 908, 'mesh': 'D008694'}, {'text': 'METH', 'type': 'Chemical', 'start': 910, 'end': 914, 'mesh': 'D008694'}, {'text': 'psychosis', 'type': 'Disease', 'start': 924, 'end': 933, 'mesh': 'D011605'}, {'text': 'paranoid type schizophrenia', 'type': 'Disease', 'start': 958, 'end': 985, 'mesh': 'D012563'}, {'text': '5-HT', 'type': 'Chemical', 'start': 1049, 'end': 1053, 'mesh': 'D012701'}, {'text': 'METH', 'type': 'Chemical', 'start': 1072, 'end': 1076, 'mesh': 'D008694'}, {'text': 'psychosis', 'type': 'Disease', 'start': 1085, 'end': 1094, 'mesh': 'D011605'}, {'text': 'METH', 'type': 'Chemical', 'start': 1261, 'end': 1265, 'mesh': 'D008694'}, {'text': 'psychosis', 'type': 'Disease', 'start': 1274, 'end': 1283, 'mesh': 'D011605'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 1412, 'end': 1427, 'mesh': 'D008694'}, {'text': 'METH', 'type': 'Chemical', 'start': 1488, 'end': 1492, 'mesh': 'D008694'}, {'text': 'psychosis', 'type': 'Disease', 'start': 1501, 'end': 1510, 'mesh': 'D011605'}, {'text': 'METH', 'type': 'Chemical', 'start': 1807, 'end': 1811, 'mesh': 'D008694'}, {'text': 'psychosis', 'type': 'Disease', 'start': 1820, 'end': 1829, 'mesh': 'D011605'}, {'text': 'METH', 'type': 'Chemical', 'start': 1924, 'end': 1928, 'mesh': 'D008694'}, {'text': 'psychosis', 'type': 'Disease', 'start': 1937, 'end': 1946, 'mesh': 'D011605'}]"
+516,19105845,Effect of increasing intraperitoneal infusion rates on bupropion hydrochloride-induced seizures in mice.,"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.","[{'text': 'bupropion hydrochloride', 'type': 'Chemical', 'start': 55, 'end': 78, 'mesh': 'D016642'}, {'text': 'seizures', 'type': 'Disease', 'start': 87, 'end': 95, 'mesh': 'D012640'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 196, 'end': 205, 'mesh': 'D016642'}, {'text': 'seizures', 'type': 'Disease', 'start': 214, 'end': 222, 'mesh': 'D012640'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 294, 'end': 303, 'mesh': 'D016642'}, {'text': 'bupropion HCl', 'type': 'Chemical', 'start': 433, 'end': 446, 'mesh': 'D016642'}, {'text': 'convulsive', 'type': 'Disease', 'start': 466, 'end': 476, 'mesh': 'D012640'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 526, 'end': 535, 'mesh': 'D016642'}, {'text': 'convulsions', 'type': 'Disease', 'start': 544, 'end': 555, 'mesh': 'D012640'}, {'text': 'bupropion HCl', 'type': 'Chemical', 'start': 686, 'end': 699, 'mesh': 'D016642'}, {'text': 'Bupropion HCl', 'type': 'Chemical', 'start': 800, 'end': 813, 'mesh': 'D016642'}, {'text': 'convulsions', 'type': 'Disease', 'start': 1030, 'end': 1041, 'mesh': 'D012640'}, {'text': 'convulsions', 'type': 'Disease', 'start': 1056, 'end': 1067, 'mesh': 'D012640'}, {'text': 'bupropion HCl', 'type': 'Chemical', 'start': 1137, 'end': 1150, 'mesh': 'D016642'}, {'text': 'convulsions', 'type': 'Disease', 'start': 1188, 'end': 1199, 'mesh': 'D012640'}, {'text': 'bupropion HCl', 'type': 'Chemical', 'start': 1402, 'end': 1415, 'mesh': 'D016642'}, {'text': 'convulsions', 'type': 'Disease', 'start': 1468, 'end': 1479, 'mesh': 'D012640'}, {'text': 'convulsions', 'type': 'Disease', 'start': 1622, 'end': 1633, 'mesh': 'D012640'}, {'text': 'convulsive', 'type': 'Disease', 'start': 1774, 'end': 1784, 'mesh': 'D012640'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 1793, 'end': 1802, 'mesh': 'D016642'}, {'text': 'convulsions', 'type': 'Disease', 'start': 1819, 'end': 1830, 'mesh': 'D012640'}]"
+517,18657397,Detailed spectral profile analysis of penicillin-induced epileptiform activity in anesthetized rats.,"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.","[{'text': 'penicillin', 'type': 'Chemical', 'start': 38, 'end': 48, 'mesh': 'D010406'}, {'text': 'epileptiform activity', 'type': 'Disease', 'start': 57, 'end': 78, 'mesh': 'D004827'}, {'text': 'Penicillin', 'type': 'Chemical', 'start': 101, 'end': 111, 'mesh': 'D010406'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 158, 'end': 166, 'mesh': 'D004827'}, {'text': 'penicillin', 'type': 'Chemical', 'start': 250, 'end': 260, 'mesh': 'D010406'}, {'text': 'epileptiform activity', 'type': 'Disease', 'start': 269, 'end': 290, 'mesh': 'D004827'}, {'text': 'urethane', 'type': 'Chemical', 'start': 405, 'end': 413, 'mesh': 'D014520'}, {'text': 'epileptic', 'type': 'Disease', 'start': 510, 'end': 519, 'mesh': 'D004827'}, {'text': 'penicillin-G potassium', 'type': 'Chemical', 'start': 566, 'end': 588, 'mesh': 'D010400'}, {'text': 'penicillin', 'type': 'Chemical', 'start': 714, 'end': 724, 'mesh': 'D010406'}, {'text': 'epileptiform activity', 'type': 'Disease', 'start': 733, 'end': 754, 'mesh': 'D004827'}, {'text': 'epileptiform activity', 'type': 'Disease', 'start': 1138, 'end': 1159, 'mesh': 'D004827'}, {'text': 'epileptiform activity', 'type': 'Disease', 'start': 1296, 'end': 1317, 'mesh': 'D004827'}, {'text': 'epilepsies', 'type': 'Disease', 'start': 1566, 'end': 1576, 'mesh': 'D004827'}]"
+518,18363626,High dose dexmedetomidine as the sole sedative for pediatric MRI.,"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.","[{'text': 'dexmedetomidine', 'type': 'Chemical', 'start': 10, 'end': 25, 'mesh': 'D020927'}, {'text': 'dexmedetomidine', 'type': 'Chemical', 'start': 149, 'end': 164, 'mesh': 'D020927'}, {'text': 'dexmedetomidine', 'type': 'Chemical', 'start': 276, 'end': 291, 'mesh': 'D020927'}, {'text': 'Dexmedetomidine', 'type': 'Chemical', 'start': 371, 'end': 386, 'mesh': 'D020927'}, {'text': 'dexmedetomidine', 'type': 'Chemical', 'start': 548, 'end': 563, 'mesh': 'D020927'}, {'text': 'dexmedetomidine', 'type': 'Chemical', 'start': 816, 'end': 831, 'mesh': 'D020927'}, {'text': 'dexmedetomidine', 'type': 'Chemical', 'start': 932, 'end': 947, 'mesh': 'D020927'}, {'text': 'dexmedetomidine', 'type': 'Chemical', 'start': 1200, 'end': 1215, 'mesh': 'D020927'}, {'text': 'pentobarbital', 'type': 'Chemical', 'start': 1293, 'end': 1306, 'mesh': 'D010424'}, {'text': 'dexmedetomidine', 'type': 'Chemical', 'start': 1345, 'end': 1360, 'mesh': 'D020927'}, {'text': 'dexmedetomidine', 'type': 'Chemical', 'start': 1436, 'end': 1451, 'mesh': 'D020927'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 1500, 'end': 1511, 'mesh': 'D001919'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 1608, 'end': 1614, 'mesh': 'D010100'}, {'text': 'Dexmedetomidine', 'type': 'Chemical', 'start': 1659, 'end': 1674, 'mesh': 'D020927'}, {'text': 'dexmedetomidine', 'type': 'Chemical', 'start': 1766, 'end': 1781, 'mesh': 'D020927'}, {'text': 'Dexmedetomidine', 'type': 'Chemical', 'start': 1977, 'end': 1992, 'mesh': 'D020927'}]"
+519,16192988,Methamphetamine causes alterations in the MAP kinase-related pathways in the brains of mice that display increased aggressiveness.,"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.","[{'text': 'Methamphetamine', 'type': 'Chemical', 'start': 0, 'end': 15, 'mesh': 'D008694'}, {'text': 'aggressiveness', 'type': 'Disease', 'start': 115, 'end': 129, 'mesh': 'D001523'}, {'text': 'Aggressive behaviors', 'type': 'Disease', 'start': 131, 'end': 151, 'mesh': 'D001523'}, {'text': 'psychiatric disorders', 'type': 'Disease', 'start': 204, 'end': 225, 'mesh': 'D001523'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 245, 'end': 260, 'mesh': 'D008694'}, {'text': 'METH', 'type': 'Chemical', 'start': 262, 'end': 266, 'mesh': 'D008694'}, {'text': 'METH', 'type': 'Chemical', 'start': 340, 'end': 344, 'mesh': 'D008694'}, {'text': 'aggressiveness', 'type': 'Disease', 'start': 369, 'end': 383, 'mesh': 'D001523'}, {'text': 'aggressiveness', 'type': 'Disease', 'start': 420, 'end': 434, 'mesh': 'D001523'}, {'text': 'METH', 'type': 'Chemical', 'start': 456, 'end': 460, 'mesh': 'D008694'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 469, 'end': 482, 'mesh': 'D006948'}, {'text': 'METH', 'type': 'Chemical', 'start': 650, 'end': 654, 'mesh': 'D008694'}, {'text': 'METH', 'type': 'Chemical', 'start': 820, 'end': 824, 'mesh': 'D008694'}, {'text': 'METH', 'type': 'Chemical', 'start': 892, 'end': 896, 'mesh': 'D008694'}, {'text': 'METH', 'type': 'Chemical', 'start': 960, 'end': 964, 'mesh': 'D008694'}, {'text': 'METH', 'type': 'Chemical', 'start': 1095, 'end': 1099, 'mesh': 'D008694'}, {'text': 'aggressive behaviors', 'type': 'Disease', 'start': 1252, 'end': 1272, 'mesh': 'D001523'}]"
+520,16157917,Lamotrigine associated with exacerbation or de novo myoclonus in idiopathic generalized epilepsies.,"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.","[{'text': 'Lamotrigine', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'C047781'}, {'text': 'myoclonus', 'type': 'Disease', 'start': 52, 'end': 61, 'mesh': 'D009207'}, {'text': 'idiopathic generalized epilepsies', 'type': 'Disease', 'start': 65, 'end': 98, 'mesh': 'C562694'}, {'text': 'idiopathic generalized epilepsies', 'type': 'Disease', 'start': 119, 'end': 152, 'mesh': 'C562694'}, {'text': 'IGE', 'type': 'Disease', 'start': 154, 'end': 157, 'mesh': 'C562694'}, {'text': 'lamotrigine', 'type': 'Chemical', 'start': 172, 'end': 183, 'mesh': 'C047781'}, {'text': 'LTG', 'type': 'Chemical', 'start': 185, 'end': 188, 'mesh': 'C047781'}, {'text': 'myoclonic jerks', 'type': 'Disease', 'start': 240, 'end': 255, 'mesh': 'D009207'}, {'text': 'MJ', 'type': 'Disease', 'start': 257, 'end': 259, 'mesh': 'D009207'}, {'text': 'LTG', 'type': 'Chemical', 'start': 281, 'end': 284, 'mesh': 'C047781'}, {'text': 'MJ', 'type': 'Disease', 'start': 297, 'end': 299, 'mesh': 'D009207'}, {'text': 'MJ', 'type': 'Disease', 'start': 368, 'end': 370, 'mesh': 'D009207'}, {'text': 'LTG', 'type': 'Chemical', 'start': 388, 'end': 391, 'mesh': 'C047781'}, {'text': 'LTG', 'type': 'Chemical', 'start': 442, 'end': 445, 'mesh': 'C047781'}, {'text': 'MJ', 'type': 'Disease', 'start': 458, 'end': 460, 'mesh': 'D009207'}, {'text': 'myoclonic status', 'type': 'Disease', 'start': 503, 'end': 519, 'mesh': 'D009207'}, {'text': 'LTG', 'type': 'Chemical', 'start': 543, 'end': 546, 'mesh': 'C047781'}]"
+521,16116131,rTMS of supplementary motor area modulates therapy-induced dyskinesias in Parkinson disease.,"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.","[{'text': 'dyskinesias', 'type': 'Disease', 'start': 59, 'end': 70, 'mesh': 'D004409'}, {'text': 'Parkinson disease', 'type': 'Disease', 'start': 74, 'end': 91, 'mesh': 'D010300'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 141, 'end': 149, 'mesh': 'D007980'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 158, 'end': 168, 'mesh': 'D004409'}, {'text': 'Parkinson disease', 'type': 'Disease', 'start': 317, 'end': 334, 'mesh': 'D010300'}, {'text': 'dyskinetic', 'type': 'Disease', 'start': 434, 'end': 444, 'mesh': 'D004409'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 473, 'end': 484, 'mesh': 'D001058'}, {'text': 'drug-induced dyskinesias', 'type': 'Disease', 'start': 540, 'end': 564, 'mesh': 'D004409'}]"
+522,15930398,Assessment of the onset and persistence of amnesia during procedural sedation with propofol.,"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.","[{'text': 'amnesia', 'type': 'Disease', 'start': 43, 'end': 50, 'mesh': 'D000647'}, {'text': 'propofol', 'type': 'Chemical', 'start': 83, 'end': 91, 'mesh': 'D015742'}, {'text': 'propofol', 'type': 'Chemical', 'start': 220, 'end': 228, 'mesh': 'D015742'}, {'text': 'propofol', 'type': 'Chemical', 'start': 461, 'end': 469, 'mesh': 'D015742'}, {'text': 'inability to repeat words', 'type': 'Disease', 'start': 1967, 'end': 1992, 'mesh': 'D000647'}, {'text': 'retrograde amnesia', 'type': 'Disease', 'start': 2870, 'end': 2888, 'mesh': 'D000648'}]"
+523,15867025,Assessment of perinatal hepatitis B and rubella prevention in New Hampshire delivery hospitals.,"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.","[{'text': 'hepatitis B', 'type': 'Disease', 'start': 24, 'end': 35, 'mesh': 'D006509'}, {'text': 'rubella', 'type': 'Disease', 'start': 40, 'end': 47, 'mesh': 'D012409'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 164, 'end': 175, 'mesh': 'D006509'}, {'text': 'rubella', 'type': 'Disease', 'start': 180, 'end': 187, 'mesh': 'D012409'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 429, 'end': 440, 'mesh': 'D006509'}, {'text': 'rubella', 'type': 'Disease', 'start': 445, 'end': 452, 'mesh': 'D012409'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 476, 'end': 487, 'mesh': 'D006509'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 541, 'end': 552, 'mesh': 'D006509'}, {'text': 'hepatitis B surface antigen', 'type': 'Chemical', 'start': 597, 'end': 624, 'mesh': 'D006514'}, {'text': 'rubella', 'type': 'Disease', 'start': 643, 'end': 650, 'mesh': 'D012409'}, {'text': 'rubella', 'type': 'Disease', 'start': 706, 'end': 713, 'mesh': 'D012409'}, {'text': 'rubella', 'type': 'Disease', 'start': 725, 'end': 732, 'mesh': 'D012409'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 788, 'end': 799, 'mesh': 'D006509'}, {'text': 'rubella', 'type': 'Disease', 'start': 812, 'end': 819, 'mesh': 'D012409'}, {'text': 'Hepatitis B', 'type': 'Disease', 'start': 839, 'end': 850, 'mesh': 'D006509'}, {'text': 'hepatitis B surface antigen', 'type': 'Chemical', 'start': 941, 'end': 968, 'mesh': 'D006514'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 1000, 'end': 1011, 'mesh': 'D006509'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 1151, 'end': 1162, 'mesh': 'D006509'}, {'text': 'rubella', 'type': 'Disease', 'start': 1466, 'end': 1473, 'mesh': 'D012409'}, {'text': 'rubella', 'type': 'Disease', 'start': 1517, 'end': 1524, 'mesh': 'D012409'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 1719, 'end': 1730, 'mesh': 'D006509'}, {'text': 'rubella', 'type': 'Disease', 'start': 1735, 'end': 1742, 'mesh': 'D012409'}]"
+524,14975762,Expression of p300 protects cardiac myocytes from apoptosis in vivo.,"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.","[{'text': 'Doxorubicin', 'type': 'Chemical', 'start': 69, 'end': 80, 'mesh': 'D004317'}, {'text': 'tumor', 'type': 'Disease', 'start': 92, 'end': 97, 'mesh': 'D009369'}, {'text': 'Doxorubicin', 'type': 'Chemical', 'start': 191, 'end': 202, 'mesh': 'D004317'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 394, 'end': 405, 'mesh': 'D004317'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 522, 'end': 533, 'mesh': 'D004317'}, {'text': 'Doxorubicin', 'type': 'Chemical', 'start': 724, 'end': 735, 'mesh': 'D004317'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1027, 'end': 1038, 'mesh': 'D004317'}, {'text': 'heart failure', 'type': 'Disease', 'start': 1089, 'end': 1102, 'mesh': 'D006333'}]"
+525,14736955,Mitochondrial DNA and its respiratory chain products are defective in doxorubicin nephrosis.,"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.","[{'text': 'doxorubicin', 'type': 'Chemical', 'start': 70, 'end': 81, 'mesh': 'D004317'}, {'text': 'nephrosis', 'type': 'Disease', 'start': 82, 'end': 91, 'mesh': 'D009401'}, {'text': 'Doxorubicin', 'type': 'Chemical', 'start': 105, 'end': 116, 'mesh': 'D004317'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 145, 'end': 156, 'mesh': 'D007674'}, {'text': 'glomerular and late-onset tubular lesions', 'type': 'Disease', 'start': 180, 'end': 221, 'mesh': 'D007674'}, {'text': 'mitochondrial injury', 'type': 'Disease', 'start': 269, 'end': 289, 'mesh': 'D028361'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 365, 'end': 376, 'mesh': 'D004317'}, {'text': 'Glomerular and tubular injury', 'type': 'Disease', 'start': 634, 'end': 663, 'mesh': 'D007674'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 833, 'end': 843, 'mesh': 'D013481'}, {'text': 'glomerular and tubular lesions', 'type': 'Disease', 'start': 950, 'end': 980, 'mesh': 'D007674'}, {'text': 'citrate', 'type': 'Chemical', 'start': 1084, 'end': 1091, 'mesh': 'C102006'}, {'text': 'tubular lesions', 'type': 'Disease', 'start': 1254, 'end': 1269, 'mesh': 'D007674'}, {'text': 'glomerular lesions', 'type': 'Disease', 'start': 1294, 'end': 1312, 'mesh': 'D007674'}, {'text': 'glomerular and tubular injury', 'type': 'Disease', 'start': 1342, 'end': 1371, 'mesh': 'D007674'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 1576, 'end': 1586, 'mesh': 'D013481'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 2002, 'end': 2012, 'mesh': 'D013481'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 2016, 'end': 2027, 'mesh': 'D004317'}, {'text': 'renal lesions', 'type': 'Disease', 'start': 2036, 'end': 2049, 'mesh': 'D007674'}]"
+526,11573852,Amphotericin B-induced seizures in a patient with AIDS.,"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.","[{'text': 'Amphotericin B', 'type': 'Chemical', 'start': 0, 'end': 14, 'mesh': 'D000666'}, {'text': 'seizures', 'type': 'Disease', 'start': 23, 'end': 31, 'mesh': 'D012640'}, {'text': 'AIDS', 'type': 'Disease', 'start': 50, 'end': 54, 'mesh': 'D000163'}, {'text': 'seizure', 'type': 'Disease', 'start': 108, 'end': 115, 'mesh': 'D012640'}, {'text': 'AIDS', 'type': 'Disease', 'start': 131, 'end': 135, 'mesh': 'D000163'}, {'text': 'amphotericin B', 'type': 'Chemical', 'start': 153, 'end': 167, 'mesh': 'D000666'}, {'text': 'grand mal seizures', 'type': 'Disease', 'start': 249, 'end': 267, 'mesh': 'D004830'}, {'text': 'amphotericin B', 'type': 'Chemical', 'start': 299, 'end': 313, 'mesh': 'D000666'}, {'text': 'seizures', 'type': 'Disease', 'start': 330, 'end': 338, 'mesh': 'D012640'}, {'text': 'didanosine', 'type': 'Chemical', 'start': 461, 'end': 471, 'mesh': 'D016049'}, {'text': 'hydroxyzine', 'type': 'Chemical', 'start': 473, 'end': 484, 'mesh': 'D006919'}, {'text': 'promethazine', 'type': 'Chemical', 'start': 486, 'end': 498, 'mesh': 'D011398'}, {'text': 'hydrocortisone', 'type': 'Chemical', 'start': 500, 'end': 514, 'mesh': 'D006854'}, {'text': 'prochlorperazine', 'type': 'Chemical', 'start': 520, 'end': 536, 'mesh': 'D011346'}, {'text': 'phenytoin', 'type': 'Chemical', 'start': 564, 'end': 573, 'mesh': 'D010672'}, {'text': 'lorazepam', 'type': 'Chemical', 'start': 578, 'end': 587, 'mesh': 'D008140'}, {'text': 'seizures', 'type': 'Disease', 'start': 593, 'end': 601, 'mesh': 'D012640'}, {'text': 'amphotercin B', 'type': 'Chemical', 'start': 637, 'end': 650, 'mesh': 'D000666'}, {'text': 'AIDS', 'type': 'Disease', 'start': 679, 'end': 683, 'mesh': 'D000163'}, {'text': 'cryptococcal meningitis', 'type': 'Disease', 'start': 688, 'end': 711, 'mesh': 'D016919'}, {'text': 'seizures', 'type': 'Disease', 'start': 766, 'end': 774, 'mesh': 'D012640'}, {'text': 'alcohol abuse', 'type': 'Disease', 'start': 805, 'end': 818, 'mesh': 'D000437'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 820, 'end': 827, 'mesh': 'D000431'}, {'text': 'seizures', 'type': 'Disease', 'start': 872, 'end': 880, 'mesh': 'D012640'}, {'text': 'Didanosine', 'type': 'Chemical', 'start': 882, 'end': 892, 'mesh': 'D016049'}, {'text': 'seizures', 'type': 'Disease', 'start': 927, 'end': 935, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 978, 'end': 985, 'mesh': 'D012640'}, {'text': 'amphotericin B', 'type': 'Chemical', 'start': 1043, 'end': 1057, 'mesh': 'D000666'}, {'text': 'seizures', 'type': 'Disease', 'start': 1079, 'end': 1087, 'mesh': 'D012640'}, {'text': 'AIDS', 'type': 'Disease', 'start': 1096, 'end': 1100, 'mesh': 'D000163'}, {'text': 'Amphotericin B', 'type': 'Chemical', 'start': 1123, 'end': 1137, 'mesh': 'D000666'}, {'text': 'seizures', 'type': 'Disease', 'start': 1176, 'end': 1184, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 1215, 'end': 1223, 'mesh': 'D012640'}, {'text': 'amphotericin B', 'type': 'Chemical', 'start': 1240, 'end': 1254, 'mesh': 'D000666'}]"
+527,9875685,Therapeutic drug monitoring of tobramycin: once-daily versus twice-daily dosage schedules.,"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.","[{'text': 'tobramycin', 'type': 'Chemical', 'start': 31, 'end': 41, 'mesh': 'D014031'}, {'text': 'tobramicyn', 'type': 'Chemical', 'start': 175, 'end': 185, 'mesh': 'D014031'}, {'text': 'toxicity', 'type': 'Disease', 'start': 227, 'end': 235, 'mesh': 'D064420'}, {'text': 'tobramycin', 'type': 'Chemical', 'start': 300, 'end': 310, 'mesh': 'D014031'}, {'text': 'tobramycin', 'type': 'Chemical', 'start': 404, 'end': 414, 'mesh': 'D014031'}, {'text': 'Tobramycin', 'type': 'Chemical', 'start': 490, 'end': 500, 'mesh': 'D014031'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1478, 'end': 1488, 'mesh': 'D003404'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1577, 'end': 1591, 'mesh': 'D007674'}, {'text': 'decreased auditory function', 'type': 'Disease', 'start': 1631, 'end': 1658, 'mesh': 'D034381'}, {'text': 'auditory loss', 'type': 'Disease', 'start': 1691, 'end': 1704, 'mesh': 'D034381'}, {'text': 'decreased auditory function', 'type': 'Disease', 'start': 1767, 'end': 1794, 'mesh': 'D034381'}, {'text': 'tobramycin', 'type': 'Chemical', 'start': 1870, 'end': 1880, 'mesh': 'D014031'}]"
+528,9848575,Chronic effects of a novel synthetic anthracycline derivative (SM-5887) on normal heart and doxorubicin-induced cardiomyopathy in beagle dogs.,"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.","[{'text': 'anthracycline', 'type': 'Chemical', 'start': 37, 'end': 50, 'mesh': 'D018943'}, {'text': 'SM-5887', 'type': 'Chemical', 'start': 63, 'end': 70, 'mesh': 'C055866'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 92, 'end': 103, 'mesh': 'D004317'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 112, 'end': 126, 'mesh': 'D009202'}, {'text': 'cardiotoxic', 'type': 'Disease', 'start': 194, 'end': 205, 'mesh': 'D066126'}, {'text': 'SM-5887', 'type': 'Chemical', 'start': 219, 'end': 226, 'mesh': 'C055866'}, {'text': 'SM-5887', 'type': 'Chemical', 'start': 266, 'end': 273, 'mesh': 'C055866'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 287, 'end': 301, 'mesh': 'D066126'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 317, 'end': 328, 'mesh': 'D004317'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 467, 'end': 478, 'mesh': 'D004317'}, {'text': 'SM-5887', 'type': 'Chemical', 'start': 494, 'end': 501, 'mesh': 'C055866'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 620, 'end': 631, 'mesh': 'D004317'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 742, 'end': 756, 'mesh': 'D009202'}, {'text': 'SM-5887', 'type': 'Chemical', 'start': 815, 'end': 822, 'mesh': 'C055866'}, {'text': 'cardiotoxic', 'type': 'Disease', 'start': 958, 'end': 969, 'mesh': 'D066126'}, {'text': 'SM-5887', 'type': 'Chemical', 'start': 980, 'end': 987, 'mesh': 'C055866'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 999, 'end': 1013, 'mesh': 'D009202'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1053, 'end': 1064, 'mesh': 'D004317'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1149, 'end': 1160, 'mesh': 'D004317'}, {'text': 'SM-5887', 'type': 'Chemical', 'start': 1176, 'end': 1183, 'mesh': 'C055866'}, {'text': 'cardiotoxic', 'type': 'Disease', 'start': 1230, 'end': 1241, 'mesh': 'D066126'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1282, 'end': 1293, 'mesh': 'D004317'}, {'text': 'SM-5887', 'type': 'Chemical', 'start': 1326, 'end': 1333, 'mesh': 'C055866'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 1374, 'end': 1388, 'mesh': 'D009202'}, {'text': 'SM-5887', 'type': 'Chemical', 'start': 1405, 'end': 1412, 'mesh': 'C055866'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1452, 'end': 1466, 'mesh': 'D066126'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1495, 'end': 1506, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1515, 'end': 1529, 'mesh': 'D066126'}]"
+529,9321531,Posteroventral medial pallidotomy in advanced Parkinson's disease.,"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.","[{'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 46, 'end': 65, 'mesh': 'D010300'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 179, 'end': 198, 'mesh': 'D010300'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 319, 'end': 338, 'mesh': 'D010300'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 1009, 'end': 1020, 'mesh': 'D004409'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 1121, 'end': 1132, 'mesh': 'D004409'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 1217, 'end': 1228, 'mesh': 'D004409'}, {'text': 'parkinsonism', 'type': 'Disease', 'start': 1265, 'end': 1277, 'mesh': 'D010300'}, {'text': 'bradykinesia', 'type': 'Disease', 'start': 1293, 'end': 1305, 'mesh': 'D018476'}, {'text': 'rigidity', 'type': 'Disease', 'start': 1311, 'end': 1319, 'mesh': 'D009127'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 1408, 'end': 1419, 'mesh': 'D004409'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 1847, 'end': 1866, 'mesh': 'D010300'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1902, 'end': 1910, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 1919, 'end': 1930, 'mesh': 'D004409'}]"
+530,9305828,Neuropeptide-Y immunoreactivity in the pilocarpine model of temporal lobe epilepsy.,"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.","[{'text': 'pilocarpine', 'type': 'Chemical', 'start': 39, 'end': 50, 'mesh': 'D010862'}, {'text': 'temporal lobe epilepsy', 'type': 'Disease', 'start': 60, 'end': 82, 'mesh': 'D004833'}, {'text': 'temporal lobe epilepsy', 'type': 'Disease', 'start': 205, 'end': 227, 'mesh': 'D004833'}, {'text': 'TLE', 'type': 'Disease', 'start': 229, 'end': 232, 'mesh': 'D004833'}, {'text': 'seizure', 'type': 'Disease', 'start': 331, 'end': 338, 'mesh': 'D012640'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 415, 'end': 426, 'mesh': 'D010862'}, {'text': 'PILO', 'type': 'Chemical', 'start': 428, 'end': 432, 'mesh': 'D010862'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 443, 'end': 451, 'mesh': 'D004827'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 491, 'end': 509, 'mesh': 'D013226'}, {'text': 'seizures', 'type': 'Disease', 'start': 544, 'end': 552, 'mesh': 'D012640'}, {'text': 'brain damage', 'type': 'Disease', 'start': 565, 'end': 577, 'mesh': 'D001930'}, {'text': 'PILO', 'type': 'Chemical', 'start': 678, 'end': 682, 'mesh': 'D010862'}, {'text': 'PILO', 'type': 'Chemical', 'start': 993, 'end': 997, 'mesh': 'D010862'}, {'text': 'PILO', 'type': 'Chemical', 'start': 1284, 'end': 1288, 'mesh': 'D010862'}, {'text': 'TLE', 'type': 'Disease', 'start': 1298, 'end': 1301, 'mesh': 'D004833'}]"
+531,9041081,Effect of myopic excimer laser photorefractive keratectomy on the electrophysiologic function of the retina and optic nerve.,"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.","[{'text': 'steroid', 'type': 'Chemical', 'start': 737, 'end': 744, 'mesh': 'D013256'}, {'text': 'elevated intraocular pressure', 'type': 'Disease', 'start': 753, 'end': 782, 'mesh': 'D009798'}, {'text': 'corticosteroid', 'type': 'Chemical', 'start': 809, 'end': 823, 'mesh': 'D000305'}, {'text': 'steroid', 'type': 'Chemical', 'start': 1101, 'end': 1108, 'mesh': 'D013256'}, {'text': 'IOP rise', 'type': 'Disease', 'start': 1117, 'end': 1125, 'mesh': 'D009798'}]"
+532,8305357,Liposomal daunorubicin in advanced Kaposi's sarcoma: a phase II study.,"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.","[{'text': 'daunorubicin', 'type': 'Chemical', 'start': 10, 'end': 22, 'mesh': 'D003630'}, {'text': ""Kaposi's sarcoma"", 'type': 'Disease', 'start': 35, 'end': 51, 'mesh': 'D012514'}, {'text': 'daunorubicin', 'type': 'Chemical', 'start': 169, 'end': 181, 'mesh': 'D003630'}, {'text': 'AIDS', 'type': 'Disease', 'start': 214, 'end': 218, 'mesh': 'D000163'}, {'text': ""Kaposi's sarcoma"", 'type': 'Disease', 'start': 227, 'end': 243, 'mesh': 'D012514'}, {'text': ""Kaposi's sarcoma"", 'type': 'Disease', 'start': 281, 'end': 297, 'mesh': 'D012514'}, {'text': 'oedema', 'type': 'Disease', 'start': 364, 'end': 370, 'mesh': 'D004487'}, {'text': 'toxicities', 'type': 'Disease', 'start': 456, 'end': 466, 'mesh': 'D064420'}, {'text': ""Kaposi's sarcoma"", 'type': 'Disease', 'start': 604, 'end': 620, 'mesh': 'D012514'}, {'text': 'toxicity', 'type': 'Disease', 'start': 771, 'end': 779, 'mesh': 'D064420'}, {'text': 'toxicity', 'type': 'Disease', 'start': 829, 'end': 837, 'mesh': 'D064420'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 879, 'end': 890, 'mesh': 'D009503'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 952, 'end': 966, 'mesh': 'D066126'}, {'text': 'daunorubicin', 'type': 'Chemical', 'start': 1008, 'end': 1020, 'mesh': 'D003630'}, {'text': ""Kaposi's sarcoma"", 'type': 'Disease', 'start': 1083, 'end': 1099, 'mesh': 'D012514'}]"
+533,8012887,Failure of ancrod in the treatment of heparin-induced arterial thrombosis.,"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.","[{'text': 'heparin', 'type': 'Chemical', 'start': 38, 'end': 45, 'mesh': 'D006493'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 63, 'end': 73, 'mesh': 'D013927'}, {'text': 'heparin', 'type': 'Chemical', 'start': 119, 'end': 126, 'mesh': 'D006493'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 135, 'end': 145, 'mesh': 'D013927'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 269, 'end': 279, 'mesh': 'D013927'}, {'text': 'heparin', 'type': 'Chemical', 'start': 297, 'end': 304, 'mesh': 'D006493'}, {'text': 'platelet aggregation', 'type': 'Disease', 'start': 313, 'end': 333, 'mesh': 'D001791'}, {'text': 'heparin', 'type': 'Chemical', 'start': 366, 'end': 373, 'mesh': 'D006493'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 426, 'end': 436, 'mesh': 'D013927'}, {'text': 'heparin', 'type': 'Chemical', 'start': 543, 'end': 550, 'mesh': 'D006493'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 559, 'end': 569, 'mesh': 'D013927'}]"
+534,7651879,Seizure after flumazenil administration in a pediatric patient.,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.,"[{'text': 'Seizure', 'type': 'Disease', 'start': 0, 'end': 7, 'mesh': 'D012640'}, {'text': 'flumazenil', 'type': 'Chemical', 'start': 14, 'end': 24, 'mesh': 'D005442'}, {'text': 'Flumazenil', 'type': 'Chemical', 'start': 64, 'end': 74, 'mesh': 'D005442'}, {'text': 'benzodiazepine', 'type': 'Chemical', 'start': 80, 'end': 94, 'mesh': 'D001569'}, {'text': 'respiratory depression', 'type': 'Disease', 'start': 144, 'end': 166, 'mesh': 'D012131'}, {'text': 'benzodiazepines', 'type': 'Chemical', 'start': 178, 'end': 193, 'mesh': 'D001569'}, {'text': 'Seizures', 'type': 'Disease', 'start': 195, 'end': 203, 'mesh': 'D012640'}, {'text': 'cardiac arrhythmias', 'type': 'Disease', 'start': 208, 'end': 227, 'mesh': 'D001145'}, {'text': 'Overdose', 'type': 'Disease', 'start': 272, 'end': 280, 'mesh': 'D062787'}, {'text': 'flumazenil', 'type': 'Chemical', 'start': 435, 'end': 445, 'mesh': 'D005442'}, {'text': 'tonic-clonic seizure', 'type': 'Disease', 'start': 501, 'end': 521, 'mesh': 'D012640'}, {'text': 'flumazenil', 'type': 'Chemical', 'start': 577, 'end': 587, 'mesh': 'D005442'}]"
+535,3015327,Remodelling of nerve structure in experimental isoniazid neuropathy in the rat.,"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.","[{'text': 'isoniazid', 'type': 'Chemical', 'start': 47, 'end': 56, 'mesh': 'D007538'}, {'text': 'neuropathy', 'type': 'Disease', 'start': 57, 'end': 67, 'mesh': 'D009422'}, {'text': 'neuropathy', 'type': 'Disease', 'start': 84, 'end': 94, 'mesh': 'D009422'}, {'text': 'isoniazid', 'type': 'Chemical', 'start': 122, 'end': 131, 'mesh': 'D007538'}]"
+536,2980315,"Selective injection of iopentol, iohexol and metrizoate into the left coronary artery of the dog. Induction of ventricular fibrillation and decrease of aortic pressure.","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.","[{'text': 'iopentol', 'type': 'Chemical', 'start': 23, 'end': 31, 'mesh': 'C053571'}, {'text': 'iohexol', 'type': 'Chemical', 'start': 33, 'end': 40, 'mesh': 'D007472'}, {'text': 'metrizoate', 'type': 'Chemical', 'start': 45, 'end': 55, 'mesh': 'D008794'}, {'text': 'ventricular fibrillation', 'type': 'Disease', 'start': 111, 'end': 135, 'mesh': 'D014693'}, {'text': 'iopentol', 'type': 'Chemical', 'start': 257, 'end': 265, 'mesh': 'C053571'}, {'text': 'iohexol', 'type': 'Chemical', 'start': 267, 'end': 274, 'mesh': 'D007472'}, {'text': 'metrizoate', 'type': 'Chemical', 'start': 279, 'end': 289, 'mesh': 'D008794'}, {'text': 'iopentol', 'type': 'Chemical', 'start': 335, 'end': 343, 'mesh': 'C053571'}, {'text': 'iohexol', 'type': 'Chemical', 'start': 359, 'end': 366, 'mesh': 'D007472'}, {'text': 'metrizoate', 'type': 'Chemical', 'start': 385, 'end': 395, 'mesh': 'D008794'}, {'text': 'ventricular fibrillation', 'type': 'Disease', 'start': 433, 'end': 457, 'mesh': 'D014693'}, {'text': 'iopentol', 'type': 'Chemical', 'start': 508, 'end': 516, 'mesh': 'C053571'}, {'text': 'iohexol', 'type': 'Chemical', 'start': 526, 'end': 533, 'mesh': 'D007472'}, {'text': 'metrizoate', 'type': 'Chemical', 'start': 550, 'end': 560, 'mesh': 'D008794'}, {'text': 'Iopentol', 'type': 'Chemical', 'start': 568, 'end': 576, 'mesh': 'C053571'}, {'text': 'iohexol', 'type': 'Chemical', 'start': 581, 'end': 588, 'mesh': 'D007472'}, {'text': 'metrizoate', 'type': 'Chemical', 'start': 661, 'end': 671, 'mesh': 'D008794'}]"
+537,2819587,"Magnetic resonance imaging of cerebral venous thrombosis secondary to ""low-dose"" birth control pills.","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.","[{'text': 'venous thrombosis', 'type': 'Disease', 'start': 39, 'end': 56, 'mesh': 'D020246'}, {'text': 'deep venous thrombosis', 'type': 'Disease', 'start': 153, 'end': 175, 'mesh': 'D020246'}, {'text': 'oral contraceptive', 'type': 'Chemical', 'start': 375, 'end': 393, 'mesh': 'D003276'}]"
+538,1564236,Relation of perfusion defects observed with myocardial contrast echocardiography to the severity of coronary stenosis: correlation with thallium-201 single-photon emission tomography.,"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.","[{'text': 'coronary stenosis', 'type': 'Disease', 'start': 100, 'end': 117, 'mesh': 'D023921'}, {'text': 'thallium', 'type': 'Chemical', 'start': 136, 'end': 144, 'mesh': 'D013793'}, {'text': 'coronary occlusion', 'type': 'Disease', 'start': 345, 'end': 363, 'mesh': 'D054059'}, {'text': 'coronary stenoses', 'type': 'Disease', 'start': 380, 'end': 397, 'mesh': 'D023921'}, {'text': 'hyperemic', 'type': 'Disease', 'start': 417, 'end': 426, 'mesh': 'D006940'}, {'text': 'coronary stenosis', 'type': 'Disease', 'start': 662, 'end': 679, 'mesh': 'D023921'}, {'text': 'thallium', 'type': 'Chemical', 'start': 838, 'end': 846, 'mesh': 'D013793'}, {'text': 'coronary occlusion', 'type': 'Disease', 'start': 920, 'end': 938, 'mesh': 'D054059'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 1176, 'end': 1188, 'mesh': 'D004176'}, {'text': 'hyperemia', 'type': 'Disease', 'start': 1197, 'end': 1206, 'mesh': 'D006940'}, {'text': 'coronary stenosis', 'type': 'Disease', 'start': 1241, 'end': 1258, 'mesh': 'D023921'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 1430, 'end': 1442, 'mesh': 'D004176'}, {'text': 'hyperemia', 'type': 'Disease', 'start': 1451, 'end': 1460, 'mesh': 'D006940'}, {'text': 'Thallium', 'type': 'Chemical', 'start': 1589, 'end': 1597, 'mesh': 'D013793'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 1671, 'end': 1683, 'mesh': 'D004176'}, {'text': 'hyperemia', 'type': 'Disease', 'start': 1692, 'end': 1701, 'mesh': 'D006940'}, {'text': 'coronary stenosis', 'type': 'Disease', 'start': 2053, 'end': 2070, 'mesh': 'D023921'}, {'text': 'thallium', 'type': 'Chemical', 'start': 2173, 'end': 2181, 'mesh': 'D013793'}]"
+539,1300436,Potential deleterious effect of furosemide in radiocontrast nephropathy.,"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.","[{'text': 'furosemide', 'type': 'Chemical', 'start': 32, 'end': 42, 'mesh': 'D005665'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 60, 'end': 71, 'mesh': 'D007674'}, {'text': 'furosemide', 'type': 'Chemical', 'start': 131, 'end': 141, 'mesh': 'D005665'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 211, 'end': 222, 'mesh': 'D007674'}, {'text': 'renal insufficiency', 'type': 'Disease', 'start': 314, 'end': 333, 'mesh': 'D051437'}, {'text': 'furosemide', 'type': 'Chemical', 'start': 532, 'end': 542, 'mesh': 'D005665'}, {'text': 'Renal function significantly deteriorated', 'type': 'Disease', 'start': 815, 'end': 856, 'mesh': 'D058186'}, {'text': 'furosemide', 'type': 'Chemical', 'start': 886, 'end': 896, 'mesh': 'D005665'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 940, 'end': 950, 'mesh': 'D003404'}, {'text': 'Renal failure', 'type': 'Disease', 'start': 1083, 'end': 1096, 'mesh': 'D051437'}, {'text': 'weight loss', 'type': 'Disease', 'start': 1117, 'end': 1128, 'mesh': 'D015431'}, {'text': 'furosemide', 'type': 'Chemical', 'start': 1136, 'end': 1146, 'mesh': 'D005665'}, {'text': 'Furosemide', 'type': 'Chemical', 'start': 1162, 'end': 1172, 'mesh': 'D005665'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1227, 'end': 1238, 'mesh': 'D007674'}]"
+540,1141447,The renal pathology in a case of lithium-induced diabetes insipidus.,"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.","[{'text': 'lithium', 'type': 'Chemical', 'start': 33, 'end': 40, 'mesh': 'D008094'}, {'text': 'diabetes insipidus', 'type': 'Disease', 'start': 49, 'end': 67, 'mesh': 'D003919'}, {'text': 'lithium', 'type': 'Chemical', 'start': 79, 'end': 86, 'mesh': 'D008094'}, {'text': 'diabetes insipidus', 'type': 'Disease', 'start': 95, 'end': 113, 'mesh': 'D003919'}, {'text': 'lithium', 'type': 'Chemical', 'start': 292, 'end': 299, 'mesh': 'D008094'}]"
+541,188339,Etiologic factors in the pathogenesis of liver tumors associated with oral contraceptives.,"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.","[{'text': 'liver tumors', 'type': 'Disease', 'start': 41, 'end': 53, 'mesh': 'D008113'}, {'text': 'oral contraceptives', 'type': 'Chemical', 'start': 70, 'end': 89, 'mesh': 'D003276'}, {'text': 'liver tumors', 'type': 'Disease', 'start': 138, 'end': 150, 'mesh': 'D008113'}, {'text': 'oral contraceptive', 'type': 'Chemical', 'start': 187, 'end': 205, 'mesh': 'D003276'}, {'text': 'steroids', 'type': 'Chemical', 'start': 206, 'end': 214, 'mesh': 'D013256'}, {'text': 'Liver Tumors', 'type': 'Disease', 'start': 233, 'end': 245, 'mesh': 'D008113'}, {'text': 'Oral Contraceptives', 'type': 'Chemical', 'start': 262, 'end': 281, 'mesh': 'D003276'}, {'text': 'focal nodular hyperplasia', 'type': 'Disease', 'start': 469, 'end': 494, 'mesh': 'D020518'}, {'text': 'adenoma', 'type': 'Disease', 'start': 496, 'end': 503, 'mesh': 'D000236'}, {'text': 'hamartoma', 'type': 'Disease', 'start': 505, 'end': 514, 'mesh': 'D006222'}, {'text': 'hepatoma', 'type': 'Disease', 'start': 520, 'end': 528, 'mesh': 'D006528'}, {'text': 'oral contraceptive', 'type': 'Chemical', 'start': 613, 'end': 631, 'mesh': 'D003276'}, {'text': 'steroids', 'type': 'Chemical', 'start': 632, 'end': 640, 'mesh': 'D013256'}, {'text': 'rupture', 'type': 'Disease', 'start': 665, 'end': 672, 'mesh': 'D012421'}]"
+542,19135948,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.,"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.","[{'text': 'Graft-versus-host disease', 'type': 'Disease', 'start': 0, 'end': 25, 'mesh': 'D006086'}, {'text': 'everolimus', 'type': 'Chemical', 'start': 43, 'end': 53, 'mesh': 'C107135'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 58, 'end': 68, 'mesh': 'D016559'}, {'text': 'sinusoidal obstruction syndrome', 'type': 'Disease', 'start': 108, 'end': 139, 'mesh': 'D006504'}, {'text': 'microangiopathy', 'type': 'Disease', 'start': 144, 'end': 159, 'mesh': 'D014652'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 227, 'end': 239, 'mesh': 'D008727'}, {'text': 'graft-versus-host disease', 'type': 'Disease', 'start': 272, 'end': 297, 'mesh': 'D006086'}, {'text': 'GVHD', 'type': 'Disease', 'start': 299, 'end': 303, 'mesh': 'D006086'}, {'text': 'Everolimus', 'type': 'Chemical', 'start': 370, 'end': 380, 'mesh': 'C107135'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 398, 'end': 407, 'mesh': 'D020123'}, {'text': 'everolimus', 'type': 'Chemical', 'start': 478, 'end': 488, 'mesh': 'C107135'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 493, 'end': 503, 'mesh': 'D016559'}, {'text': 'myelodysplastic syndrome', 'type': 'Disease', 'start': 554, 'end': 578, 'mesh': 'D009190'}, {'text': 'MDS', 'type': 'Disease', 'start': 580, 'end': 583, 'mesh': 'D009190'}, {'text': 'acute myeloid leukemia', 'type': 'Disease', 'start': 596, 'end': 618, 'mesh': 'D015470'}, {'text': 'AML', 'type': 'Disease', 'start': 620, 'end': 623, 'mesh': 'D015470'}, {'text': 'mucositis', 'type': 'Disease', 'start': 798, 'end': 807, 'mesh': 'D052016'}, {'text': 'GVHD', 'type': 'Disease', 'start': 857, 'end': 861, 'mesh': 'D006086'}, {'text': 'GVHD', 'type': 'Disease', 'start': 929, 'end': 933, 'mesh': 'D006086'}, {'text': 'Transplantation-associated microangiopathy', 'type': 'Disease', 'start': 935, 'end': 977, 'mesh': 'D014652'}, {'text': 'TMA', 'type': 'Disease', 'start': 979, 'end': 982, 'mesh': 'D014652'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 1030, 'end': 1049, 'mesh': 'D058186'}, {'text': 'sinusoidal obstruction syndrome', 'type': 'Disease', 'start': 1137, 'end': 1168, 'mesh': 'D006504'}, {'text': 'SOS', 'type': 'Disease', 'start': 1170, 'end': 1173, 'mesh': 'D006504'}, {'text': 'GVHD', 'type': 'Disease', 'start': 1374, 'end': 1378, 'mesh': 'D006086'}, {'text': 'TMA', 'type': 'Disease', 'start': 1397, 'end': 1400, 'mesh': 'D014652'}, {'text': 'SOS', 'type': 'Disease', 'start': 1405, 'end': 1408, 'mesh': 'D006504'}]"
+543,14704468,Effect of some convulsants on the protective activity of loreclezole and its combinations with valproate or clonazepam in amygdala-kindled rats.,"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.","[{'text': 'loreclezole', 'type': 'Chemical', 'start': 57, 'end': 68, 'mesh': 'C066440'}, {'text': 'valproate', 'type': 'Chemical', 'start': 95, 'end': 104, 'mesh': 'D014635'}, {'text': 'clonazepam', 'type': 'Chemical', 'start': 108, 'end': 118, 'mesh': 'D002998'}, {'text': 'Loreclezole', 'type': 'Chemical', 'start': 145, 'end': 156, 'mesh': 'C066440'}, {'text': 'seizure', 'type': 'Disease', 'start': 247, 'end': 254, 'mesh': 'D012640'}, {'text': 'loreclezole', 'type': 'Chemical', 'start': 305, 'end': 316, 'mesh': 'C066440'}, {'text': 'valproate', 'type': 'Chemical', 'start': 334, 'end': 343, 'mesh': 'D014635'}, {'text': 'clonazepam', 'type': 'Chemical', 'start': 345, 'end': 355, 'mesh': 'D002998'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 360, 'end': 373, 'mesh': 'D002220'}, {'text': 'bicuculline', 'type': 'Chemical', 'start': 572, 'end': 583, 'mesh': 'D001640'}, {'text': 'N-methyl-D-aspartic acid', 'type': 'Chemical', 'start': 585, 'end': 609, 'mesh': 'D016202'}, {'text': 'BAY k-8644', 'type': 'Chemical', 'start': 614, 'end': 624, 'mesh': 'D001498'}, {'text': 'calcium', 'type': 'Chemical', 'start': 647, 'end': 654, 'mesh': 'D002118'}, {'text': 'loreclezole', 'type': 'Chemical', 'start': 701, 'end': 712, 'mesh': 'C066440'}, {'text': 'valproate', 'type': 'Chemical', 'start': 744, 'end': 753, 'mesh': 'D014635'}, {'text': 'bicuculline', 'type': 'Chemical', 'start': 774, 'end': 785, 'mesh': 'D001640'}, {'text': 'aminophylline', 'type': 'Chemical', 'start': 787, 'end': 800, 'mesh': 'D000628'}, {'text': 'BAY k-8644', 'type': 'Chemical', 'start': 805, 'end': 815, 'mesh': 'D001498'}, {'text': 'loreclezole', 'type': 'Chemical', 'start': 855, 'end': 866, 'mesh': 'C066440'}, {'text': 'clonazepam', 'type': 'Chemical', 'start': 881, 'end': 891, 'mesh': 'D002998'}, {'text': 'loreclezole', 'type': 'Chemical', 'start': 960, 'end': 971, 'mesh': 'C066440'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1101, 'end': 1108, 'mesh': 'D002118'}]"
+544,12549952,Acute liver failure with concurrent bupropion and carbimazole therapy.,"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.","[{'text': 'Acute liver failure', 'type': 'Disease', 'start': 0, 'end': 19, 'mesh': 'D017114'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 36, 'end': 45, 'mesh': 'D016642'}, {'text': 'carbimazole', 'type': 'Chemical', 'start': 50, 'end': 61, 'mesh': 'D002231'}, {'text': 'liver failure', 'type': 'Disease', 'start': 108, 'end': 121, 'mesh': 'D017093'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 165, 'end': 174, 'mesh': 'D016642'}, {'text': 'carbimazole', 'type': 'Chemical', 'start': 179, 'end': 190, 'mesh': 'D002231'}, {'text': 'hyperthyroidism', 'type': 'Disease', 'start': 250, 'end': 265, 'mesh': 'D006980'}, {'text': 'carbimazole', 'type': 'Chemical', 'start': 288, 'end': 299, 'mesh': 'D002231'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 304, 'end': 315, 'mesh': 'D011433'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 369, 'end': 378, 'mesh': 'D016642'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 456, 'end': 475, 'mesh': 'D017114'}, {'text': 'drug-induced acute liver injury', 'type': 'Disease', 'start': 564, 'end': 595, 'mesh': 'D056486'}, {'text': 'sepsis', 'type': 'Disease', 'start': 638, 'end': 644, 'mesh': 'D018805'}, {'text': 'coagulopathy', 'type': 'Disease', 'start': 649, 'end': 661, 'mesh': 'D001778'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 735, 'end': 744, 'mesh': 'D016642'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 753, 'end': 767, 'mesh': 'D056486'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 890, 'end': 904, 'mesh': 'D056486'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 916, 'end': 925, 'mesh': 'D016642'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 992, 'end': 1011, 'mesh': 'D017114'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 1035, 'end': 1044, 'mesh': 'D016642'}, {'text': 'carbimazole', 'type': 'Chemical', 'start': 1081, 'end': 1092, 'mesh': 'D002231'}, {'text': 'acute liver insult', 'type': 'Disease', 'start': 1156, 'end': 1174, 'mesh': 'D017114'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 1186, 'end': 1195, 'mesh': 'D016642'}, {'text': 'hepatotoxic', 'type': 'Disease', 'start': 1226, 'end': 1237, 'mesh': 'D056486'}]"
+545,19370593,Long term hormone therapy for perimenopausal and postmenopausal women.,"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.","[{'text': 'cardiovascular disease', 'type': 'Disease', 'start': 215, 'end': 237, 'mesh': 'D002318'}, {'text': 'osteoporosis', 'type': 'Disease', 'start': 239, 'end': 251, 'mesh': 'D010024'}, {'text': 'dementia', 'type': 'Disease', 'start': 256, 'end': 264, 'mesh': 'D003704'}, {'text': 'cancer', 'type': 'Disease', 'start': 453, 'end': 459, 'mesh': 'D009369'}, {'text': 'gallbladder disease', 'type': 'Disease', 'start': 461, 'end': 480, 'mesh': 'D005705'}, {'text': 'fractures', 'type': 'Disease', 'start': 493, 'end': 502, 'mesh': 'D050723'}, {'text': 'Menstrual Disorders', 'type': 'Disease', 'start': 627, 'end': 646, 'mesh': 'D008599'}, {'text': 'oestrogens', 'type': 'Chemical', 'start': 975, 'end': 985, 'mesh': 'D004967'}, {'text': 'progestogens', 'type': 'Chemical', 'start': 1003, 'end': 1015, 'mesh': 'D011374'}, {'text': 'venous thrombo-embolism', 'type': 'Disease', 'start': 1330, 'end': 1353, 'mesh': 'D054556'}, {'text': 'stroke', 'type': 'Disease', 'start': 1396, 'end': 1402, 'mesh': 'D020521'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 1424, 'end': 1437, 'mesh': 'D001943'}, {'text': 'gallbladder disease', 'type': 'Disease', 'start': 1442, 'end': 1461, 'mesh': 'D005705'}, {'text': 'oestrogen', 'type': 'Chemical', 'start': 1473, 'end': 1482, 'mesh': 'D004967'}, {'text': 'venous thrombo-embolism', 'type': 'Disease', 'start': 1527, 'end': 1550, 'mesh': 'D054556'}, {'text': 'stroke', 'type': 'Disease', 'start': 1552, 'end': 1558, 'mesh': 'D020521'}, {'text': 'gallbladder disease', 'type': 'Disease', 'start': 1563, 'end': 1582, 'mesh': 'D005705'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 1703, 'end': 1716, 'mesh': 'D001943'}, {'text': 'fractures', 'type': 'Disease', 'start': 1798, 'end': 1807, 'mesh': 'D050723'}, {'text': 'colon cancer', 'type': 'Disease', 'start': 1830, 'end': 1842, 'mesh': 'D003110'}, {'text': 'dementia', 'type': 'Disease', 'start': 2063, 'end': 2071, 'mesh': 'D003704'}, {'text': 'cardiovascular disease', 'type': 'Disease', 'start': 2090, 'end': 2112, 'mesh': 'D002318'}, {'text': 'venous thrombo-embolism', 'type': 'Disease', 'start': 2190, 'end': 2213, 'mesh': 'D054556'}, {'text': 'oestrogen', 'type': 'Chemical', 'start': 2340, 'end': 2349, 'mesh': 'D004967'}, {'text': 'venous thrombo-embolism', 'type': 'Disease', 'start': 2451, 'end': 2474, 'mesh': 'D054556'}]"
+546,17019386,Passage of mannitol into the brain around gliomas: a potential cause of rebound phenomenon. A study on 21 patients.,"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.","[{'text': 'mannitol', 'type': 'Chemical', 'start': 11, 'end': 19, 'mesh': 'D008353'}, {'text': 'gliomas', 'type': 'Disease', 'start': 42, 'end': 49, 'mesh': 'D005910'}, {'text': 'mannitol', 'type': 'Chemical', 'start': 139, 'end': 147, 'mesh': 'D008353'}, {'text': 'brain edema', 'type': 'Disease', 'start': 158, 'end': 169, 'mesh': 'D001929'}, {'text': 'elevated ICP', 'type': 'Disease', 'start': 180, 'end': 192, 'mesh': 'D019586'}, {'text': 'brain tumor', 'type': 'Disease', 'start': 196, 'end': 207, 'mesh': 'D001932'}, {'text': 'mannitol', 'type': 'Chemical', 'start': 291, 'end': 299, 'mesh': 'D008353'}, {'text': 'mannitol', 'type': 'Chemical', 'start': 573, 'end': 581, 'mesh': 'D008353'}, {'text': 'brain tumor', 'type': 'Disease', 'start': 624, 'end': 635, 'mesh': 'D001932'}, {'text': 'Mannitol', 'type': 'Chemical', 'start': 655, 'end': 663, 'mesh': 'D008353'}, {'text': 'malignant glioma', 'type': 'Disease', 'start': 736, 'end': 752, 'mesh': 'D005910'}, {'text': 'metastases', 'type': 'Disease', 'start': 766, 'end': 776, 'mesh': 'D009362'}, {'text': 'meningioma', 'type': 'Disease', 'start': 786, 'end': 796, 'mesh': 'D008579'}, {'text': 'edematous', 'type': 'Disease', 'start': 880, 'end': 889, 'mesh': 'D004487'}, {'text': 'Mannitol', 'type': 'Chemical', 'start': 962, 'end': 970, 'mesh': 'D008353'}, {'text': 'glioma', 'type': 'Disease', 'start': 1106, 'end': 1112, 'mesh': 'D005910'}, {'text': 'mannitol', 'type': 'Chemical', 'start': 1123, 'end': 1131, 'mesh': 'D008353'}, {'text': 'meningioma', 'type': 'Disease', 'start': 1224, 'end': 1234, 'mesh': 'D008579'}, {'text': 'metastases', 'type': 'Disease', 'start': 1239, 'end': 1249, 'mesh': 'D009362'}, {'text': 'mannitol', 'type': 'Chemical', 'start': 1284, 'end': 1292, 'mesh': 'D008353'}, {'text': 'mannitol', 'type': 'Chemical', 'start': 1474, 'end': 1482, 'mesh': 'D008353'}, {'text': 'gliomas', 'type': 'Disease', 'start': 1521, 'end': 1528, 'mesh': 'D005910'}, {'text': 'edema', 'type': 'Disease', 'start': 1610, 'end': 1615, 'mesh': 'D004487'}]"
+547,12452237,Can lidocaine reduce succinylcholine induced postoperative myalgia?,"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.","[{'text': 'lidocaine', 'type': 'Chemical', 'start': 4, 'end': 13, 'mesh': 'D008012'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 21, 'end': 36, 'mesh': 'D013390'}, {'text': 'postoperative myalgia', 'type': 'Disease', 'start': 45, 'end': 66, 'mesh': 'D010149'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 121, 'end': 130, 'mesh': 'D008012'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 160, 'end': 175, 'mesh': 'D013390'}, {'text': 'myalgia', 'type': 'Disease', 'start': 184, 'end': 191, 'mesh': 'D063806'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 442, 'end': 457, 'mesh': 'D013390'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 485, 'end': 494, 'mesh': 'D008012'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 515, 'end': 530, 'mesh': 'D013390'}, {'text': 'rocuronium', 'type': 'Chemical', 'start': 576, 'end': 586, 'mesh': 'C061870'}, {'text': 'Morphine', 'type': 'Chemical', 'start': 604, 'end': 612, 'mesh': 'D009020'}, {'text': 'thiopental', 'type': 'Chemical', 'start': 799, 'end': 809, 'mesh': 'D013874'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 826, 'end': 841, 'mesh': 'D013390'}, {'text': 'rocuronium', 'type': 'Chemical', 'start': 860, 'end': 870, 'mesh': 'C061870'}, {'text': 'fasciculation', 'type': 'Disease', 'start': 977, 'end': 990, 'mesh': 'D005207'}, {'text': 'myalgia', 'type': 'Disease', 'start': 1211, 'end': 1218, 'mesh': 'D063806'}, {'text': 'muscle fasciculation', 'type': 'Disease', 'start': 1404, 'end': 1424, 'mesh': 'D005207'}, {'text': 'muscle fasciculation', 'type': 'Disease', 'start': 1507, 'end': 1527, 'mesh': 'D005207'}, {'text': 'myalgia', 'type': 'Disease', 'start': 1590, 'end': 1597, 'mesh': 'D063806'}, {'text': 'myalgia', 'type': 'Disease', 'start': 1710, 'end': 1717, 'mesh': 'D063806'}, {'text': 'muscle fasciculation', 'type': 'Disease', 'start': 1740, 'end': 1760, 'mesh': 'D005207'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 1896, 'end': 1911, 'mesh': 'D013390'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 1921, 'end': 1930, 'mesh': 'D008012'}, {'text': 'postoperative myalgia', 'type': 'Disease', 'start': 1998, 'end': 2019, 'mesh': 'D010149'}]"
+548,9564988,Open-label assessment of levofloxacin for the treatment of acute bacterial sinusitis in adults.,"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.","[{'text': 'levofloxacin', 'type': 'Chemical', 'start': 25, 'end': 37, 'mesh': 'D064704'}, {'text': 'sinusitis', 'type': 'Disease', 'start': 75, 'end': 84, 'mesh': 'D012852'}, {'text': 'levofloxacin', 'type': 'Chemical', 'start': 144, 'end': 156, 'mesh': 'D064704'}, {'text': 'sinusitis', 'type': 'Disease', 'start': 253, 'end': 262, 'mesh': 'D012852'}, {'text': 'levofloxacin', 'type': 'Chemical', 'start': 1613, 'end': 1625, 'mesh': 'D064704'}, {'text': 'diarrhea', 'type': 'Disease', 'start': 1725, 'end': 1733, 'mesh': 'D003967'}, {'text': 'flatulence', 'type': 'Disease', 'start': 1735, 'end': 1745, 'mesh': 'D005414'}, {'text': 'nausea', 'type': 'Disease', 'start': 1751, 'end': 1757, 'mesh': 'D009325'}, {'text': 'levofloxacin', 'type': 'Chemical', 'start': 1866, 'end': 1878, 'mesh': 'D064704'}, {'text': 'sinusitis', 'type': 'Disease', 'start': 1952, 'end': 1961, 'mesh': 'D012852'}]"
+549,7596955,Clinical evaluation on combined administration of oral prostacyclin analogue beraprost and phosphodiesterase inhibitor cilostazol.,"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.","[{'text': 'prostacyclin', 'type': 'Chemical', 'start': 55, 'end': 67, 'mesh': 'D011464'}, {'text': 'beraprost', 'type': 'Chemical', 'start': 77, 'end': 86, 'mesh': 'C048081'}, {'text': 'cilostazol', 'type': 'Chemical', 'start': 119, 'end': 129, 'mesh': 'C045645'}, {'text': 'prostacyclin', 'type': 'Chemical', 'start': 190, 'end': 202, 'mesh': 'D011464'}, {'text': 'beraprost', 'type': 'Chemical', 'start': 212, 'end': 221, 'mesh': 'C048081'}, {'text': 'BPT', 'type': 'Chemical', 'start': 223, 'end': 226, 'mesh': 'C048081'}, {'text': 'cilostazol', 'type': 'Chemical', 'start': 269, 'end': 279, 'mesh': 'C045645'}, {'text': 'CLZ', 'type': 'Chemical', 'start': 281, 'end': 284, 'mesh': 'C045645'}, {'text': 'cAMP', 'type': 'Chemical', 'start': 381, 'end': 385, 'mesh': 'D000242'}, {'text': ""cyclic adenosine 3',5'-monophosphate"", 'type': 'Chemical', 'start': 387, 'end': 423, 'mesh': 'D000242'}, {'text': 'BPT', 'type': 'Chemical', 'start': 564, 'end': 567, 'mesh': 'C048081'}, {'text': 'CLZ', 'type': 'Chemical', 'start': 568, 'end': 571, 'mesh': 'C045645'}, {'text': 'BPT', 'type': 'Chemical', 'start': 599, 'end': 602, 'mesh': 'C048081'}, {'text': 'CLZ', 'type': 'Chemical', 'start': 671, 'end': 674, 'mesh': 'C045645'}, {'text': 'platelet aggregation', 'type': 'Disease', 'start': 789, 'end': 809, 'mesh': 'D001791'}, {'text': 'cAMP', 'type': 'Chemical', 'start': 845, 'end': 849, 'mesh': 'D000242'}, {'text': 'headache', 'type': 'Disease', 'start': 993, 'end': 1001, 'mesh': 'D006261'}, {'text': 'facial flush', 'type': 'Disease', 'start': 1035, 'end': 1047, 'mesh': 'D005483'}, {'text': 'nausea', 'type': 'Disease', 'start': 1059, 'end': 1065, 'mesh': 'D009325'}, {'text': 'CLZ', 'type': 'Chemical', 'start': 1104, 'end': 1107, 'mesh': 'C045645'}, {'text': 'cAMP', 'type': 'Chemical', 'start': 1267, 'end': 1271, 'mesh': 'D000242'}, {'text': 'BPT', 'type': 'Chemical', 'start': 1652, 'end': 1655, 'mesh': 'C048081'}, {'text': 'CLZ', 'type': 'Chemical', 'start': 1656, 'end': 1659, 'mesh': 'C045645'}]"
+550,17965424,Gastrointestinal tolerability of etoricoxib in rheumatoid arthritis patients: results of the etoricoxib vs diclofenac sodium gastrointestinal tolerability and effectiveness trial (EDGE-II).,"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.","[{'text': 'etoricoxib', 'type': 'Chemical', 'start': 33, 'end': 43, 'mesh': 'C422649'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 47, 'end': 67, 'mesh': 'D001172'}, {'text': 'etoricoxib', 'type': 'Chemical', 'start': 93, 'end': 103, 'mesh': 'C422649'}, {'text': 'diclofenac sodium', 'type': 'Chemical', 'start': 107, 'end': 124, 'mesh': 'D004008'}, {'text': 'etoricoxib', 'type': 'Chemical', 'start': 308, 'end': 318, 'mesh': 'C422649'}, {'text': 'diclofenac', 'type': 'Chemical', 'start': 323, 'end': 333, 'mesh': 'D004008'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 351, 'end': 371, 'mesh': 'D001172'}, {'text': 'RA', 'type': 'Disease', 'start': 373, 'end': 375, 'mesh': 'D001172'}, {'text': 'RA', 'type': 'Disease', 'start': 462, 'end': 464, 'mesh': 'D001172'}, {'text': 'etoricoxib', 'type': 'Chemical', 'start': 492, 'end': 502, 'mesh': 'C422649'}, {'text': 'diclofenac', 'type': 'Chemical', 'start': 529, 'end': 539, 'mesh': 'D004008'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 614, 'end': 621, 'mesh': 'D001241'}, {'text': 'thrombotic cardiovascular', 'type': 'Disease', 'start': 848, 'end': 873, 'mesh': 'D002318'}, {'text': 'etoricoxib', 'type': 'Chemical', 'start': 1097, 'end': 1107, 'mesh': 'C422649'}, {'text': 'diclofenac', 'type': 'Chemical', 'start': 1112, 'end': 1122, 'mesh': 'D004008'}, {'text': 'GI AEs', 'type': 'Disease', 'start': 1188, 'end': 1194, 'mesh': 'D005767'}, {'text': 'etoricoxib', 'type': 'Chemical', 'start': 1224, 'end': 1234, 'mesh': 'C422649'}, {'text': 'diclofenac', 'type': 'Chemical', 'start': 1240, 'end': 1250, 'mesh': 'D004008'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1398, 'end': 1410, 'mesh': 'D006973'}, {'text': 'oedema', 'type': 'Disease', 'start': 1423, 'end': 1429, 'mesh': 'D004487'}, {'text': 'etoricoxib', 'type': 'Chemical', 'start': 1473, 'end': 1483, 'mesh': 'C422649'}, {'text': 'diclofenac', 'type': 'Chemical', 'start': 1527, 'end': 1537, 'mesh': 'D004008'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1579, 'end': 1591, 'mesh': 'D006973'}, {'text': 'oedema', 'type': 'Disease', 'start': 1607, 'end': 1613, 'mesh': 'D004487'}, {'text': 'Etoricoxib', 'type': 'Chemical', 'start': 1616, 'end': 1626, 'mesh': 'C422649'}, {'text': 'diclofenac', 'type': 'Chemical', 'start': 1631, 'end': 1641, 'mesh': 'D004008'}, {'text': 'Etoricoxib', 'type': 'Chemical', 'start': 1759, 'end': 1769, 'mesh': 'C422649'}, {'text': 'GI AEs', 'type': 'Disease', 'start': 1851, 'end': 1857, 'mesh': 'D005767'}, {'text': 'diclofenac', 'type': 'Chemical', 'start': 1872, 'end': 1882, 'mesh': 'D004008'}, {'text': 'GI AEs', 'type': 'Disease', 'start': 1979, 'end': 1985, 'mesh': 'D005767'}, {'text': 'etoricoxib', 'type': 'Chemical', 'start': 2018, 'end': 2028, 'mesh': 'C422649'}]"
+551,17042884,Placebo-level incidence of extrapyramidal symptoms (EPS) with quetiapine in controlled studies of patients with bipolar mania.,"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.","[{'text': 'extrapyramidal symptoms', 'type': 'Disease', 'start': 27, 'end': 50, 'mesh': 'D001480'}, {'text': 'EPS', 'type': 'Disease', 'start': 52, 'end': 55, 'mesh': 'D001480'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 62, 'end': 72, 'mesh': 'C069541'}, {'text': 'bipolar mania', 'type': 'Disease', 'start': 112, 'end': 125, 'mesh': 'D001714'}, {'text': 'extrapyramidal symptoms', 'type': 'Disease', 'start': 151, 'end': 174, 'mesh': 'D001480'}, {'text': 'EPS', 'type': 'Disease', 'start': 176, 'end': 179, 'mesh': 'D001480'}, {'text': 'akathisia', 'type': 'Disease', 'start': 192, 'end': 201, 'mesh': 'D017109'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 208, 'end': 218, 'mesh': 'C069541'}, {'text': 'bipolar mania', 'type': 'Disease', 'start': 236, 'end': 249, 'mesh': 'D001714'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 380, 'end': 390, 'mesh': 'C069541'}, {'text': 'lithium', 'type': 'Chemical', 'start': 463, 'end': 470, 'mesh': 'D008094'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 474, 'end': 485, 'mesh': 'D006220'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 551, 'end': 561, 'mesh': 'C069541'}, {'text': 'lithium', 'type': 'Chemical', 'start': 620, 'end': 627, 'mesh': 'D008094'}, {'text': 'divalproex', 'type': 'Chemical', 'start': 631, 'end': 641, 'mesh': 'D014635'}, {'text': 'QTP', 'type': 'Chemical', 'start': 643, 'end': 646, 'mesh': 'C069541'}, {'text': 'Li', 'type': 'Chemical', 'start': 649, 'end': 651, 'mesh': 'D008094'}, {'text': 'DVP', 'type': 'Chemical', 'start': 652, 'end': 655, 'mesh': 'D014635'}, {'text': 'Li', 'type': 'Chemical', 'start': 714, 'end': 716, 'mesh': 'D008094'}, {'text': 'DVP', 'type': 'Chemical', 'start': 717, 'end': 720, 'mesh': 'D014635'}, {'text': 'Extrapyramidal symptoms', 'type': 'Disease', 'start': 733, 'end': 756, 'mesh': 'D001480'}, {'text': 'EPS', 'type': 'Disease', 'start': 931, 'end': 934, 'mesh': 'D001480'}, {'text': 'akathisia', 'type': 'Disease', 'start': 969, 'end': 978, 'mesh': 'D017109'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 1002, 'end': 1012, 'mesh': 'C069541'}, {'text': 'EPS', 'type': 'Disease', 'start': 1071, 'end': 1074, 'mesh': 'D001480'}, {'text': 'QTP', 'type': 'Chemical', 'start': 1103, 'end': 1106, 'mesh': 'C069541'}, {'text': 'Li', 'type': 'Chemical', 'start': 1109, 'end': 1111, 'mesh': 'D008094'}, {'text': 'DVP', 'type': 'Chemical', 'start': 1112, 'end': 1115, 'mesh': 'D014635'}, {'text': 'Li', 'type': 'Chemical', 'start': 1158, 'end': 1160, 'mesh': 'D008094'}, {'text': 'DVP', 'type': 'Chemical', 'start': 1161, 'end': 1164, 'mesh': 'D014635'}, {'text': 'EPS', 'type': 'Disease', 'start': 1200, 'end': 1203, 'mesh': 'D001480'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1247, 'end': 1258, 'mesh': 'D006220'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1320, 'end': 1327, 'mesh': 'D008094'}, {'text': 'EPS', 'type': 'Disease', 'start': 1387, 'end': 1390, 'mesh': 'D001480'}, {'text': 'akathisia', 'type': 'Disease', 'start': 1409, 'end': 1418, 'mesh': 'D017109'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 1444, 'end': 1454, 'mesh': 'C069541'}, {'text': 'QTP', 'type': 'Chemical', 'start': 1503, 'end': 1506, 'mesh': 'C069541'}, {'text': 'Li', 'type': 'Chemical', 'start': 1509, 'end': 1511, 'mesh': 'D008094'}, {'text': 'DVP', 'type': 'Chemical', 'start': 1512, 'end': 1515, 'mesh': 'D014635'}, {'text': 'Li', 'type': 'Chemical', 'start': 1533, 'end': 1535, 'mesh': 'D008094'}, {'text': 'DVP', 'type': 'Chemical', 'start': 1536, 'end': 1539, 'mesh': 'D014635'}, {'text': 'Lithium', 'type': 'Chemical', 'start': 1548, 'end': 1555, 'mesh': 'D008094'}, {'text': 'tremor', 'type': 'Disease', 'start': 1623, 'end': 1629, 'mesh': 'D014202'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 1643, 'end': 1653, 'mesh': 'C069541'}, {'text': 'tremor', 'type': 'Disease', 'start': 1673, 'end': 1679, 'mesh': 'D014202'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1716, 'end': 1723, 'mesh': 'D008094'}, {'text': 'tremor', 'type': 'Disease', 'start': 1770, 'end': 1776, 'mesh': 'D014202'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1799, 'end': 1806, 'mesh': 'D008094'}, {'text': 'Haloperidol', 'type': 'Chemical', 'start': 1816, 'end': 1827, 'mesh': 'D006220'}, {'text': 'akathisia', 'type': 'Disease', 'start': 1884, 'end': 1893, 'mesh': 'D017109'}, {'text': 'tremor', 'type': 'Disease', 'start': 1915, 'end': 1921, 'mesh': 'D014202'}, {'text': 'extrapyramidal syndrome', 'type': 'Disease', 'start': 1947, 'end': 1970, 'mesh': 'D001480'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 1996, 'end': 2006, 'mesh': 'C069541'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 2057, 'end': 2067, 'mesh': 'C069541'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 2149, 'end': 2159, 'mesh': 'C069541'}, {'text': 'bipolar mania', 'type': 'Disease', 'start': 2188, 'end': 2201, 'mesh': 'D001714'}, {'text': 'EPS', 'type': 'Disease', 'start': 2220, 'end': 2223, 'mesh': 'D001480'}, {'text': 'akathisia', 'type': 'Disease', 'start': 2235, 'end': 2244, 'mesh': 'D017109'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 2251, 'end': 2261, 'mesh': 'C069541'}]"
+552,8586822,Contribution of the sympathetic nervous system to salt-sensitivity in lifetime captopril-treated spontaneously hypertensive rats.,"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.","[{'text': 'captopril', 'type': 'Chemical', 'start': 79, 'end': 88, 'mesh': 'D002216'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 111, 'end': 123, 'mesh': 'D006973'}, {'text': 'captopril', 'type': 'Chemical', 'start': 182, 'end': 191, 'mesh': 'D002216'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 214, 'end': 226, 'mesh': 'D006973'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 301, 'end': 313, 'mesh': 'D006973'}, {'text': 'dietary sodium chloride', 'type': 'Chemical', 'start': 324, 'end': 347, 'mesh': 'D017673'}, {'text': 'captopril', 'type': 'Chemical', 'start': 455, 'end': 464, 'mesh': 'D002216'}, {'text': 'sodium chloride', 'type': 'Chemical', 'start': 496, 'end': 511, 'mesh': 'D012965'}, {'text': 'sodium chloride', 'type': 'Chemical', 'start': 536, 'end': 551, 'mesh': 'D012965'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 653, 'end': 662, 'mesh': 'D003000'}, {'text': 'captopril', 'type': 'Chemical', 'start': 682, 'end': 691, 'mesh': 'D002216'}, {'text': 'hexamethonium', 'type': 'Chemical', 'start': 810, 'end': 823, 'mesh': 'D018738'}, {'text': 'dietary sodium chloride', 'type': 'Chemical', 'start': 879, 'end': 902, 'mesh': 'D017673'}, {'text': 'increase in MAP', 'type': 'Disease', 'start': 911, 'end': 926, 'mesh': 'D006973'}, {'text': 'alpha2-adrenergic receptor agonist', 'type': 'Chemical', 'start': 982, 'end': 1016, 'mesh': 'D058647'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 1017, 'end': 1026, 'mesh': 'D003000'}, {'text': 'sodium chloride', 'type': 'Chemical', 'start': 1142, 'end': 1157, 'mesh': 'D012965'}, {'text': 'captopril', 'type': 'Chemical', 'start': 1194, 'end': 1203, 'mesh': 'D002216'}, {'text': 'sodium chloride', 'type': 'Chemical', 'start': 1305, 'end': 1320, 'mesh': 'D012965'}]"
+553,3961813,Dose-related beneficial and adverse effects of dietary corticosterone on organophosphorus-induced delayed neuropathy in chickens.,"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.","[{'text': 'corticosterone', 'type': 'Chemical', 'start': 55, 'end': 69, 'mesh': 'D003345'}, {'text': 'organophosphorus', 'type': 'Chemical', 'start': 73, 'end': 89, 'mesh': 'D010755'}, {'text': 'neuropathy', 'type': 'Disease', 'start': 106, 'end': 116, 'mesh': 'D009422'}, {'text': 'Tri-ortho-tolyl phosphate', 'type': 'Chemical', 'start': 130, 'end': 155, 'mesh': 'C025541'}, {'text': 'TOTP', 'type': 'Chemical', 'start': 157, 'end': 161, 'mesh': 'C025541'}, {'text': ""0,0'-diisopropyl phosphorofluoridate"", 'type': 'Chemical', 'start': 183, 'end': 219, 'mesh': 'D007531'}, {'text': 'DFP', 'type': 'Chemical', 'start': 221, 'end': 224, 'mesh': 'D007531'}, {'text': 'corticosterone', 'type': 'Chemical', 'start': 351, 'end': 365, 'mesh': 'D003345'}, {'text': 'neuropathy', 'type': 'Disease', 'start': 445, 'end': 455, 'mesh': 'D009422'}, {'text': 'corticosterone', 'type': 'Chemical', 'start': 528, 'end': 542, 'mesh': 'D003345'}, {'text': 'TOTP', 'type': 'Chemical', 'start': 569, 'end': 573, 'mesh': 'C025541'}, {'text': 'neuropathy', 'type': 'Disease', 'start': 582, 'end': 592, 'mesh': 'D009422'}, {'text': 'TOTP', 'type': 'Chemical', 'start': 679, 'end': 683, 'mesh': 'C025541'}, {'text': 'DFP', 'type': 'Chemical', 'start': 687, 'end': 690, 'mesh': 'D007531'}, {'text': 'Neurotoxic', 'type': 'Disease', 'start': 692, 'end': 702, 'mesh': 'D020258'}, {'text': 'TOTP', 'type': 'Chemical', 'start': 735, 'end': 739, 'mesh': 'C025541'}, {'text': 'DFP', 'type': 'Chemical', 'start': 743, 'end': 746, 'mesh': 'D007531'}, {'text': 'organophosphorous', 'type': 'Chemical', 'start': 807, 'end': 824, 'mesh': 'D010755'}, {'text': 'corticosterone', 'type': 'Chemical', 'start': 859, 'end': 873, 'mesh': 'D003345'}, {'text': 'TOTP', 'type': 'Chemical', 'start': 882, 'end': 886, 'mesh': 'C025541'}, {'text': 'DFP', 'type': 'Chemical', 'start': 890, 'end': 893, 'mesh': 'D007531'}, {'text': 'Degenerating myelinated fibers', 'type': 'Disease', 'start': 1019, 'end': 1049, 'mesh': 'D009410'}, {'text': 'TOTP', 'type': 'Chemical', 'start': 1128, 'end': 1132, 'mesh': 'C025541'}, {'text': 'DFP', 'type': 'Chemical', 'start': 1136, 'end': 1139, 'mesh': 'D007531'}]"
+554,20973483,In vivo characterization of a dual adenosine A2A/A1 receptor antagonist in animal models of Parkinson's disease.,"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.","[{'text': 'adenosine A2A/A1 receptor antagonist', 'type': 'Chemical', 'start': 35, 'end': 71, 'mesh': 'D058915'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 92, 'end': 111, 'mesh': 'D010300'}, {'text': 'adenosine A(2A)/A(1) receptor antagonist', 'type': 'Chemical', 'start': 152, 'end': 192, 'mesh': 'D058915'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 221, 'end': 240, 'mesh': 'D010300'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 616, 'end': 635, 'mesh': 'D010300'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 670, 'end': 681, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 690, 'end': 699, 'mesh': 'D002375'}, {'text': 'reserpine', 'type': 'Chemical', 'start': 716, 'end': 725, 'mesh': 'D012110'}, {'text': 'akinesia', 'type': 'Disease', 'start': 734, 'end': 742, 'mesh': 'D004409'}, {'text': '6-hydroxydopamine', 'type': 'Chemical', 'start': 748, 'end': 765, 'mesh': 'D016627'}, {'text': '6-OHDA', 'type': 'Chemical', 'start': 767, 'end': 773, 'mesh': 'D016627'}, {'text': 'MPTP', 'type': 'Chemical', 'start': 818, 'end': 822, 'mesh': 'D015632'}]"
+555,17511042,An extremely rare case of delusional parasitosis in a chronic hepatitis C patient during pegylated interferon alpha-2b and ribavirin treatment.,"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.","[{'text': 'delusional parasitosis', 'type': 'Disease', 'start': 26, 'end': 48, 'mesh': 'D063726'}, {'text': 'chronic hepatitis C', 'type': 'Disease', 'start': 54, 'end': 73, 'mesh': 'D019698'}, {'text': 'pegylated interferon alpha-2b', 'type': 'Chemical', 'start': 89, 'end': 118, 'mesh': 'C417083'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 123, 'end': 132, 'mesh': 'D012254'}, {'text': 'chronic hepatitis C', 'type': 'Disease', 'start': 164, 'end': 183, 'mesh': 'D019698'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 213, 'end': 222, 'mesh': 'D012254'}, {'text': 'depression', 'type': 'Disease', 'start': 309, 'end': 319, 'mesh': 'D003866'}, {'text': 'psychosis', 'type': 'Disease', 'start': 354, 'end': 363, 'mesh': 'D011605'}, {'text': 'psychogenic parasitosis', 'type': 'Disease', 'start': 407, 'end': 430, 'mesh': 'D063726'}, {'text': 'delusional parasitosis', 'type': 'Disease', 'start': 553, 'end': 575, 'mesh': 'D063726'}, {'text': 'pegylated interferon alpha-2b', 'type': 'Chemical', 'start': 598, 'end': 627, 'mesh': 'C417083'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 639, 'end': 648, 'mesh': 'D012254'}, {'text': 'pegylated interferon alpha-2b', 'type': 'Chemical', 'start': 828, 'end': 857, 'mesh': 'C417083'}]"
+556,16720068,Possible neuroleptic malignant syndrome related to concomitant treatment with paroxetine and alprazolam.,"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.","[{'text': 'neuroleptic malignant syndrome', 'type': 'Disease', 'start': 9, 'end': 39, 'mesh': 'D009459'}, {'text': 'paroxetine', 'type': 'Chemical', 'start': 78, 'end': 88, 'mesh': 'D017374'}, {'text': 'alprazolam', 'type': 'Chemical', 'start': 93, 'end': 103, 'mesh': 'D000525'}, {'text': 'depressive symptoms', 'type': 'Disease', 'start': 128, 'end': 147, 'mesh': 'D003866'}, {'text': 'psychiatric', 'type': 'Disease', 'start': 166, 'end': 177, 'mesh': 'D001523'}, {'text': 'insomnia', 'type': 'Disease', 'start': 194, 'end': 202, 'mesh': 'D007319'}, {'text': 'loss of appetite', 'type': 'Disease', 'start': 204, 'end': 220, 'mesh': 'D001068'}, {'text': 'agitation', 'type': 'Disease', 'start': 238, 'end': 247, 'mesh': 'D011595'}, {'text': 'paroxetine', 'type': 'Chemical', 'start': 306, 'end': 316, 'mesh': 'D017374'}, {'text': 'alprazolam', 'type': 'Chemical', 'start': 328, 'end': 338, 'mesh': 'D000525'}, {'text': 'paroxetine', 'type': 'Chemical', 'start': 359, 'end': 369, 'mesh': 'D017374'}, {'text': 'alprazolam', 'type': 'Chemical', 'start': 374, 'end': 384, 'mesh': 'D000525'}, {'text': 'psychomotor retardation', 'type': 'Disease', 'start': 425, 'end': 448, 'mesh': 'D011596'}, {'text': 'muscle rigidity', 'type': 'Disease', 'start': 477, 'end': 492, 'mesh': 'D009127'}, {'text': 'tremors', 'type': 'Disease', 'start': 498, 'end': 505, 'mesh': 'D014202'}, {'text': 'fever', 'type': 'Disease', 'start': 525, 'end': 530, 'mesh': 'D005334'}, {'text': 'extrapyramidal symptoms', 'type': 'Disease', 'start': 625, 'end': 648, 'mesh': 'D001480'}, {'text': 'creatine', 'type': 'Chemical', 'start': 690, 'end': 698, 'mesh': 'D003401'}, {'text': 'aspartate', 'type': 'Chemical', 'start': 726, 'end': 735, 'mesh': 'D001224'}, {'text': 'alanine', 'type': 'Chemical', 'start': 765, 'end': 772, 'mesh': 'D000409'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 851, 'end': 864, 'mesh': 'D001971'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 869, 'end': 877, 'mesh': 'D003975'}, {'text': 'fever', 'type': 'Disease', 'start': 919, 'end': 924, 'mesh': 'D005334'}, {'text': 'neuroleptic malignant syndrome', 'type': 'Disease', 'start': 1040, 'end': 1070, 'mesh': 'D009459'}, {'text': 'NMS', 'type': 'Disease', 'start': 1072, 'end': 1075, 'mesh': 'D009459'}, {'text': 'NMS', 'type': 'Disease', 'start': 1102, 'end': 1105, 'mesh': 'D009459'}, {'text': 'paroxetine', 'type': 'Chemical', 'start': 1145, 'end': 1155, 'mesh': 'D017374'}, {'text': 'alprazolam', 'type': 'Chemical', 'start': 1160, 'end': 1170, 'mesh': 'D000525'}, {'text': 'NMS', 'type': 'Disease', 'start': 1324, 'end': 1327, 'mesh': 'D009459'}, {'text': 'NMS', 'type': 'Disease', 'start': 1518, 'end': 1521, 'mesh': 'D009459'}, {'text': 'depressive', 'type': 'Disease', 'start': 1549, 'end': 1559, 'mesh': 'D003866'}, {'text': 'dehydration', 'type': 'Disease', 'start': 1598, 'end': 1609, 'mesh': 'D003681'}, {'text': 'agitation', 'type': 'Disease', 'start': 1611, 'end': 1620, 'mesh': 'D011595'}, {'text': 'malnutrition', 'type': 'Disease', 'start': 1622, 'end': 1634, 'mesh': 'D044342'}, {'text': 'depression', 'type': 'Disease', 'start': 1750, 'end': 1760, 'mesh': 'D003866'}]"
+557,16596970,Pilocarpine seizures cause age-dependent impairment in auditory location discrimination.,"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.","[{'text': 'Pilocarpine', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D010862'}, {'text': 'seizures', 'type': 'Disease', 'start': 12, 'end': 20, 'mesh': 'D012640'}, {'text': 'impairment in auditory location discrimination', 'type': 'Disease', 'start': 41, 'end': 87, 'mesh': 'D001308'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 107, 'end': 125, 'mesh': 'D013226'}, {'text': 'seizures', 'type': 'Disease', 'start': 163, 'end': 171, 'mesh': 'D012640'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 276, 'end': 294, 'mesh': 'D013226'}, {'text': 'deficits in auditory discrimination', 'type': 'Disease', 'start': 302, 'end': 337, 'mesh': 'D001308'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 465, 'end': 483, 'mesh': 'D013226'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 585, 'end': 596, 'mesh': 'D010862'}, {'text': 'Pilocarpine', 'type': 'Chemical', 'start': 612, 'end': 623, 'mesh': 'D010862'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 646, 'end': 664, 'mesh': 'D013226'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 666, 'end': 684, 'mesh': 'D013226'}, {'text': 'seizures', 'type': 'Disease', 'start': 734, 'end': 742, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 793, 'end': 801, 'mesh': 'D012640'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 962, 'end': 980, 'mesh': 'D013226'}, {'text': 'Status epilepticus', 'type': 'Disease', 'start': 1074, 'end': 1092, 'mesh': 'D013226'}, {'text': 'Status epilepticus', 'type': 'Disease', 'start': 1185, 'end': 1203, 'mesh': 'D013226'}, {'text': 'impairment in auditory discrimination', 'type': 'Disease', 'start': 1246, 'end': 1283, 'mesh': 'D001308'}, {'text': 'impaired auditory location discrimination', 'type': 'Disease', 'start': 1326, 'end': 1367, 'mesh': 'D001308'}]"
+558,16586083,Cardiovascular risk with cyclooxygenase inhibitors: general problem with substance specific differences?,"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.","[{'text': 'cyclooxygenase inhibitors', 'type': 'Chemical', 'start': 25, 'end': 50, 'mesh': 'D016861'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 190, 'end': 211, 'mesh': 'D009203'}, {'text': 'stroke', 'type': 'Disease', 'start': 213, 'end': 219, 'mesh': 'D020521'}, {'text': 'hypertension', 'type': 'Disease', 'start': 221, 'end': 233, 'mesh': 'D006973'}, {'text': 'heart failure', 'type': 'Disease', 'start': 238, 'end': 251, 'mesh': 'D006333'}, {'text': 'cyclooxygenase inhibitors', 'type': 'Chemical', 'start': 274, 'end': 299, 'mesh': 'D016861'}, {'text': 'Cyclooxygenase inhibitors', 'type': 'Chemical', 'start': 413, 'end': 438, 'mesh': 'D016861'}, {'text': 'cyclooxygenase inhibitors', 'type': 'Chemical', 'start': 735, 'end': 760, 'mesh': 'D016861'}, {'text': 'prostaglandin', 'type': 'Chemical', 'start': 912, 'end': 925, 'mesh': 'D011453'}, {'text': 'N-terminal pro brain natriuretic peptide', 'type': 'Chemical', 'start': 974, 'end': 1014, 'mesh': 'C109794'}, {'text': 'NT-proBNP', 'type': 'Chemical', 'start': 1016, 'end': 1025, 'mesh': 'C109794'}, {'text': 'cardiovascular toxicity', 'type': 'Disease', 'start': 1164, 'end': 1187, 'mesh': 'D002318'}]"
+559,10539815,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),"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.","[{'text': 'decreased renal function', 'type': 'Disease', 'start': 14, 'end': 38, 'mesh': 'D051437'}, {'text': 'heart failure', 'type': 'Disease', 'start': 56, 'end': 69, 'mesh': 'D006333'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 77, 'end': 88, 'mesh': 'D000809'}, {'text': 'left ventricular dysfunction', 'type': 'Disease', 'start': 154, 'end': 182, 'mesh': 'D018487'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 212, 'end': 223, 'mesh': 'D000809'}, {'text': 'congestive heart failure', 'type': 'Disease', 'start': 301, 'end': 325, 'mesh': 'D006333'}, {'text': 'CHF', 'type': 'Disease', 'start': 327, 'end': 330, 'mesh': 'D006333'}, {'text': 'decreased renal function', 'type': 'Disease', 'start': 351, 'end': 375, 'mesh': 'D051437'}, {'text': 'reduction in renal function', 'type': 'Disease', 'start': 533, 'end': 560, 'mesh': 'D051437'}, {'text': 'CHF', 'type': 'Disease', 'start': 578, 'end': 581, 'mesh': 'D006333'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 601, 'end': 612, 'mesh': 'D000809'}, {'text': 'Left Ventricular Dysfunction', 'type': 'Disease', 'start': 695, 'end': 723, 'mesh': 'D018487'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 789, 'end': 798, 'mesh': 'D004656'}, {'text': 'CHF', 'type': 'Disease', 'start': 820, 'end': 823, 'mesh': 'D006333'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 871, 'end': 880, 'mesh': 'D004656'}, {'text': 'Decreased renal function', 'type': 'Disease', 'start': 999, 'end': 1023, 'mesh': 'D051437'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1055, 'end': 1065, 'mesh': 'D003404'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1256, 'end': 1266, 'mesh': 'D003404'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1321, 'end': 1333, 'mesh': 'D006973'}, {'text': 'diabetes', 'type': 'Disease', 'start': 1335, 'end': 1343, 'mesh': 'D003920'}, {'text': 'diuretic', 'type': 'Chemical', 'start': 1370, 'end': 1378, 'mesh': 'D004232'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 1445, 'end': 1454, 'mesh': 'D004656'}, {'text': 'decreased renal function', 'type': 'Disease', 'start': 1487, 'end': 1511, 'mesh': 'D051437'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 1587, 'end': 1596, 'mesh': 'D004656'}, {'text': 'diuretic', 'type': 'Chemical', 'start': 1615, 'end': 1623, 'mesh': 'D004232'}, {'text': 'diabetes', 'type': 'Disease', 'start': 1637, 'end': 1645, 'mesh': 'D003920'}, {'text': 'decreased renal function', 'type': 'Disease', 'start': 1667, 'end': 1691, 'mesh': 'D051437'}, {'text': 'decreased renal function', 'type': 'Disease', 'start': 1831, 'end': 1855, 'mesh': 'D051437'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 1905, 'end': 1914, 'mesh': 'D004656'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 1922, 'end': 1931, 'mesh': 'D004656'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 2012, 'end': 2021, 'mesh': 'D004656'}, {'text': 'Diuretic', 'type': 'Chemical', 'start': 2060, 'end': 2068, 'mesh': 'D004232'}, {'text': 'decreased renal function', 'type': 'Disease', 'start': 2124, 'end': 2148, 'mesh': 'D051437'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 2156, 'end': 2165, 'mesh': 'D004656'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 2267, 'end': 2276, 'mesh': 'D004656'}, {'text': 'diabetes', 'type': 'Disease', 'start': 2409, 'end': 2417, 'mesh': 'D003920'}, {'text': 'renal impairment', 'type': 'Disease', 'start': 2435, 'end': 2451, 'mesh': 'D051437'}, {'text': 'Enalapril', 'type': 'Chemical', 'start': 2628, 'end': 2637, 'mesh': 'D004656'}, {'text': 'decreased renal function', 'type': 'Disease', 'start': 2679, 'end': 2703, 'mesh': 'D051437'}, {'text': 'CHF', 'type': 'Disease', 'start': 2721, 'end': 2724, 'mesh': 'D006333'}, {'text': 'Diuretic', 'type': 'Chemical', 'start': 2726, 'end': 2734, 'mesh': 'D004232'}, {'text': 'Diabetes', 'type': 'Disease', 'start': 2777, 'end': 2785, 'mesh': 'D003920'}, {'text': 'renal impairment', 'type': 'Disease', 'start': 2827, 'end': 2843, 'mesh': 'D051437'}, {'text': 'CHF', 'type': 'Disease', 'start': 2865, 'end': 2868, 'mesh': 'D006333'}, {'text': 'enalapril', 'type': 'Chemical', 'start': 2903, 'end': 2912, 'mesh': 'D004656'}]"
+560,9022662,Pemoline induced acute choreoathetosis: case report and review of the literature.,"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.","[{'text': 'Pemoline', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D010389'}, {'text': 'choreoathetosis', 'type': 'Disease', 'start': 23, 'end': 38, 'mesh': 'D002819|D001264'}, {'text': 'Pemoline', 'type': 'Chemical', 'start': 94, 'end': 102, 'mesh': 'D010389'}, {'text': 'oxazolidine', 'type': 'Chemical', 'start': 109, 'end': 120, 'mesh': 'C064210'}, {'text': 'amphetamines', 'type': 'Chemical', 'start': 168, 'end': 180, 'mesh': 'D000662'}, {'text': 'attention deficit disorder', 'type': 'Disease', 'start': 210, 'end': 236, 'mesh': 'D001289'}, {'text': 'Pemoline', 'type': 'Chemical', 'start': 238, 'end': 246, 'mesh': 'D010389'}, {'text': 'movement disorders', 'type': 'Disease', 'start': 318, 'end': 336, 'mesh': 'D009069'}, {'text': 'pemoline', 'type': 'Chemical', 'start': 402, 'end': 410, 'mesh': 'D010389'}, {'text': 'choreoathetosis', 'type': 'Disease', 'start': 436, 'end': 451, 'mesh': 'D002819|D001264'}, {'text': 'pemoline', 'type': 'Chemical', 'start': 596, 'end': 604, 'mesh': 'D010389'}, {'text': 'attention deficit disorder', 'type': 'Disease', 'start': 690, 'end': 716, 'mesh': 'D001289'}, {'text': 'methylphenidate', 'type': 'Chemical', 'start': 741, 'end': 756, 'mesh': 'D008774'}, {'text': 'pemoline', 'type': 'Chemical', 'start': 802, 'end': 810, 'mesh': 'D010389'}, {'text': 'choreoathetoid', 'type': 'Disease', 'start': 824, 'end': 838, 'mesh': 'D002819|D001264'}, {'text': 'movement disorders', 'type': 'Disease', 'start': 924, 'end': 942, 'mesh': 'D009069'}, {'text': 'movement disorders', 'type': 'Disease', 'start': 978, 'end': 996, 'mesh': 'D009069'}, {'text': 'benzodiazepines', 'type': 'Chemical', 'start': 1083, 'end': 1098, 'mesh': 'D001569'}, {'text': 'choreoathetoid', 'type': 'Disease', 'start': 1128, 'end': 1142, 'mesh': 'D002819|D001264'}, {'text': 'choreoathetosis', 'type': 'Disease', 'start': 1204, 'end': 1219, 'mesh': 'D002819|D001264'}, {'text': 'Pemoline', 'type': 'Chemical', 'start': 1367, 'end': 1375, 'mesh': 'D010389'}, {'text': 'movement disorder', 'type': 'Disease', 'start': 1387, 'end': 1404, 'mesh': 'D009069'}, {'text': 'choreoathetoid', 'type': 'Disease', 'start': 1485, 'end': 1499, 'mesh': 'D002819|D001264'}, {'text': 'pemoline', 'type': 'Chemical', 'start': 1560, 'end': 1568, 'mesh': 'D010389'}, {'text': 'overdose', 'type': 'Disease', 'start': 1569, 'end': 1577, 'mesh': 'D062787'}]"
+561,8677458,Continuous subcutaneous administration of mesna to prevent ifosfamide-induced hemorrhagic cystitis.,"Hemorrhagic cystitis is a major potential toxicity of ifosfamide that can be prevented by administering mesna along with the cytotoxic agent. Mesna is generally administered by the intravenous route, although experience with oral delivery of the drug has increased. The continuous subcutaneous administration of mesna has the advantage of not requiring intravenous access. In addition, subcutaneous delivery of the neutralizing agent will not be associated with the risk of inadequate urinary mesna concentrations, such as in a patient taking oral mesna who experiences severe ifosfamide-induced emesis and is unable to absorb the drug. 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.","[{'text': 'mesna', 'type': 'Chemical', 'start': 42, 'end': 47, 'mesh': 'D015080'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 59, 'end': 69, 'mesh': 'D007069'}, {'text': 'toxicity', 'type': 'Disease', 'start': 142, 'end': 150, 'mesh': 'D064420'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 154, 'end': 164, 'mesh': 'D007069'}, {'text': 'mesna', 'type': 'Chemical', 'start': 204, 'end': 209, 'mesh': 'D015080'}, {'text': 'Mesna', 'type': 'Chemical', 'start': 242, 'end': 247, 'mesh': 'D015080'}, {'text': 'mesna', 'type': 'Chemical', 'start': 412, 'end': 417, 'mesh': 'D015080'}, {'text': 'mesna', 'type': 'Chemical', 'start': 593, 'end': 598, 'mesh': 'D015080'}, {'text': 'mesna', 'type': 'Chemical', 'start': 648, 'end': 653, 'mesh': 'D015080'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 677, 'end': 687, 'mesh': 'D007069'}, {'text': 'emesis', 'type': 'Disease', 'start': 696, 'end': 702, 'mesh': 'D014839'}, {'text': 'mesna', 'type': 'Chemical', 'start': 794, 'end': 799, 'mesh': 'D015080'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 899, 'end': 909, 'mesh': 'D007069'}]"
+562,6323692,Modification of drug action by hyperammonemia.,"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.","[{'text': 'hyperammonemia', 'type': 'Disease', 'start': 31, 'end': 45, 'mesh': 'D022124'}, {'text': 'ammonium acetate', 'type': 'Chemical', 'start': 65, 'end': 81, 'mesh': 'C018824'}, {'text': 'NH4Ac', 'type': 'Chemical', 'start': 83, 'end': 88, 'mesh': 'C018824'}, {'text': 'morphine', 'type': 'Chemical', 'start': 138, 'end': 146, 'mesh': 'D009020'}, {'text': 'incoordination', 'type': 'Disease', 'start': 219, 'end': 233, 'mesh': 'D001259'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 237, 'end': 245, 'mesh': 'D003975'}, {'text': 'NH4Ac', 'type': 'Chemical', 'start': 251, 'end': 256, 'mesh': 'C018824'}, {'text': 'hyperammonemia', 'type': 'Disease', 'start': 294, 'end': 308, 'mesh': 'D022124'}, {'text': 'liver disease', 'type': 'Disease', 'start': 446, 'end': 459, 'mesh': 'D008107'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 494, 'end': 507, 'mesh': 'D000109'}, {'text': 'catecholamine', 'type': 'Chemical', 'start': 516, 'end': 529, 'mesh': 'D002395'}, {'text': 'NH4Ac', 'type': 'Chemical', 'start': 604, 'end': 609, 'mesh': 'C018824'}, {'text': 'KCl', 'type': 'Chemical', 'start': 614, 'end': 617, 'mesh': 'D011189'}, {'text': 'NH4Ac', 'type': 'Chemical', 'start': 686, 'end': 691, 'mesh': 'C018824'}, {'text': 'calcium', 'type': 'Chemical', 'start': 712, 'end': 719, 'mesh': 'D002118'}, {'text': 'depression', 'type': 'Disease', 'start': 733, 'end': 743, 'mesh': 'D003866'}, {'text': 'calcium', 'type': 'Chemical', 'start': 765, 'end': 772, 'mesh': 'D002118'}, {'text': 'catecholamine', 'type': 'Chemical', 'start': 785, 'end': 798, 'mesh': 'D002395'}, {'text': 'acetaldehyde', 'type': 'Chemical', 'start': 810, 'end': 822, 'mesh': 'D000079'}, {'text': 'NH4Ac', 'type': 'Chemical', 'start': 842, 'end': 847, 'mesh': 'C018824'}, {'text': 'ammonia', 'type': 'Chemical', 'start': 878, 'end': 885, 'mesh': 'D000641'}, {'text': 'calcium', 'type': 'Chemical', 'start': 893, 'end': 900, 'mesh': 'D002118'}, {'text': 'NH4Ac', 'type': 'Chemical', 'start': 939, 'end': 944, 'mesh': 'C018824'}, {'text': 'calcium', 'type': 'Chemical', 'start': 953, 'end': 960, 'mesh': 'D002118'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 977, 'end': 986, 'mesh': 'D014700'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 1014, 'end': 1023, 'mesh': 'D014700'}, {'text': 'NH4Ac', 'type': 'Chemical', 'start': 1044, 'end': 1049, 'mesh': 'C018824'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1072, 'end': 1080, 'mesh': 'D009020'}, {'text': 'analgesia', 'type': 'Disease', 'start': 1081, 'end': 1090, 'mesh': 'D000699'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 1096, 'end': 1104, 'mesh': 'D003975'}, {'text': 'incoordination', 'type': 'Disease', 'start': 1122, 'end': 1136, 'mesh': 'D001259'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1153, 'end': 1164, 'mesh': 'D000661'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 1201, 'end': 1210, 'mesh': 'D014700'}, {'text': 'NH4Ac', 'type': 'Chemical', 'start': 1215, 'end': 1220, 'mesh': 'C018824'}, {'text': 'metrazol', 'type': 'Chemical', 'start': 1255, 'end': 1263, 'mesh': 'D010433'}, {'text': 'hyperammonemia', 'type': 'Disease', 'start': 1287, 'end': 1301, 'mesh': 'D022124'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1311, 'end': 1318, 'mesh': 'D002118'}]"
+563,20195852,Risk of nephropathy after consumption of nonionic contrast media by children undergoing cardiac angiography: a prospective study.,"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.","[{'text': 'nephropathy', 'type': 'Disease', 'start': 8, 'end': 19, 'mesh': 'D007674'}, {'text': 'contrast media', 'type': 'Chemical', 'start': 50, 'end': 64, 'mesh': 'D003287'}, {'text': 'contrast media', 'type': 'Chemical', 'start': 169, 'end': 183, 'mesh': 'D003287'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 192, 'end': 203, 'mesh': 'D007674'}, {'text': 'CIN', 'type': 'Disease', 'start': 205, 'end': 208, 'mesh': 'D007674'}, {'text': 'CIN', 'type': 'Disease', 'start': 481, 'end': 484, 'mesh': 'D007674'}, {'text': 'contrast media', 'type': 'Chemical', 'start': 502, 'end': 516, 'mesh': 'D003287'}, {'text': 'CM', 'type': 'Chemical', 'start': 518, 'end': 520, 'mesh': 'D003287'}, {'text': 'iopromide', 'type': 'Chemical', 'start': 523, 'end': 532, 'mesh': 'C038192'}, {'text': 'iohexol', 'type': 'Chemical', 'start': 537, 'end': 544, 'mesh': 'D007472'}, {'text': 'CM', 'type': 'Chemical', 'start': 669, 'end': 671, 'mesh': 'D003287'}, {'text': 'cyanosis', 'type': 'Disease', 'start': 692, 'end': 700, 'mesh': 'D003490'}, {'text': 'iopromide', 'type': 'Chemical', 'start': 761, 'end': 770, 'mesh': 'C038192'}, {'text': 'iohexol', 'type': 'Chemical', 'start': 792, 'end': 799, 'mesh': 'D007472'}, {'text': 'sodium', 'type': 'Chemical', 'start': 825, 'end': 831, 'mesh': 'D012964'}, {'text': 'Na', 'type': 'Chemical', 'start': 833, 'end': 835, 'mesh': 'D012964'}, {'text': 'potassium', 'type': 'Chemical', 'start': 838, 'end': 847, 'mesh': 'D011188'}, {'text': 'K', 'type': 'Chemical', 'start': 849, 'end': 850, 'mesh': 'D011188'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 857, 'end': 867, 'mesh': 'D003404'}, {'text': 'Cr', 'type': 'Chemical', 'start': 869, 'end': 871, 'mesh': 'D003404'}, {'text': 'CM', 'type': 'Chemical', 'start': 989, 'end': 991, 'mesh': 'D003287'}, {'text': 'Na', 'type': 'Chemical', 'start': 1015, 'end': 1017, 'mesh': 'D012964'}, {'text': 'Cr', 'type': 'Chemical', 'start': 1022, 'end': 1024, 'mesh': 'D003404'}, {'text': 'renal failure', 'type': 'Disease', 'start': 1074, 'end': 1087, 'mesh': 'D051437'}, {'text': 'Injury to the kidney', 'type': 'Disease', 'start': 1089, 'end': 1109, 'mesh': 'D058186'}, {'text': 'Failure of kidney function', 'type': 'Disease', 'start': 1111, 'end': 1137, 'mesh': 'D051437'}, {'text': 'Loss of kidney function', 'type': 'Disease', 'start': 1139, 'end': 1162, 'mesh': 'D051437'}, {'text': 'renal damage', 'type': 'Disease', 'start': 1178, 'end': 1190, 'mesh': 'D007674'}, {'text': 'CIN', 'type': 'Disease', 'start': 1228, 'end': 1231, 'mesh': 'D007674'}, {'text': 'CIN', 'type': 'Disease', 'start': 1301, 'end': 1304, 'mesh': 'D007674'}, {'text': 'renal injury', 'type': 'Disease', 'start': 1389, 'end': 1401, 'mesh': 'D058186'}, {'text': 'renal injury', 'type': 'Disease', 'start': 1457, 'end': 1469, 'mesh': 'D058186'}, {'text': 'CIN', 'type': 'Disease', 'start': 1506, 'end': 1509, 'mesh': 'D007674'}, {'text': 'CM', 'type': 'Chemical', 'start': 1561, 'end': 1563, 'mesh': 'D003287'}, {'text': 'CIN', 'type': 'Disease', 'start': 1688, 'end': 1691, 'mesh': 'D007674'}, {'text': 'CM', 'type': 'Chemical', 'start': 1728, 'end': 1730, 'mesh': 'D003287'}, {'text': 'CIN', 'type': 'Disease', 'start': 1771, 'end': 1774, 'mesh': 'D007674'}, {'text': 'congenital heart diseases', 'type': 'Disease', 'start': 1791, 'end': 1816, 'mesh': 'D006331'}, {'text': 'CIN', 'type': 'Disease', 'start': 1945, 'end': 1948, 'mesh': 'D007674'}, {'text': 'CM', 'type': 'Chemical', 'start': 2049, 'end': 2051, 'mesh': 'D003287'}, {'text': 'cyanosis', 'type': 'Disease', 'start': 2076, 'end': 2084, 'mesh': 'D003490'}, {'text': 'CIN', 'type': 'Disease', 'start': 2099, 'end': 2102, 'mesh': 'D007674'}]"
+564,18997632,A case of ventricular tachycardia related to caffeine pretreatment.,"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.","[{'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 10, 'end': 33, 'mesh': 'D017180'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 45, 'end': 53, 'mesh': 'D002110'}, {'text': 'seizure', 'type': 'Disease', 'start': 79, 'end': 86, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 200, 'end': 207, 'mesh': 'D012640'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 232, 'end': 240, 'mesh': 'D002110'}, {'text': 'seizure', 'type': 'Disease', 'start': 269, 'end': 276, 'mesh': 'D012640'}, {'text': 'ventricular ectopy', 'type': 'Disease', 'start': 398, 'end': 416, 'mesh': 'D018879'}, {'text': 'cardiac disease', 'type': 'Disease', 'start': 468, 'end': 483, 'mesh': 'D006331'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 487, 'end': 497, 'mesh': 'D001145'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 551, 'end': 574, 'mesh': 'D017180'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 581, 'end': 589, 'mesh': 'D002110'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 627, 'end': 635, 'mesh': 'D002110'}, {'text': 'ventricular arrhythmias', 'type': 'Disease', 'start': 742, 'end': 765, 'mesh': 'D001145'}]"
+565,15565293,Optical coherence tomography can measure axonal loss in patients with ethambutol-induced optic neuropathy.,"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.","[{'text': 'ethambutol', 'type': 'Chemical', 'start': 70, 'end': 80, 'mesh': 'D004977'}, {'text': 'optic neuropathy', 'type': 'Disease', 'start': 89, 'end': 105, 'mesh': 'D009901'}, {'text': 'axonal degeneration', 'type': 'Disease', 'start': 161, 'end': 180, 'mesh': 'D009410'}, {'text': 'ethambutol', 'type': 'Chemical', 'start': 184, 'end': 194, 'mesh': 'D004977'}, {'text': 'optic neuropathy', 'type': 'Disease', 'start': 203, 'end': 219, 'mesh': 'D009901'}, {'text': 'Ethambutol', 'type': 'Chemical', 'start': 262, 'end': 272, 'mesh': 'D004977'}, {'text': 'tuberculosis', 'type': 'Disease', 'start': 323, 'end': 335, 'mesh': 'D014376'}, {'text': 'ethambutol', 'type': 'Chemical', 'start': 363, 'end': 373, 'mesh': 'D004977'}, {'text': 'optic neuropathy', 'type': 'Disease', 'start': 380, 'end': 396, 'mesh': 'D009901'}, {'text': 'optic neuropathy', 'type': 'Disease', 'start': 499, 'end': 515, 'mesh': 'D009901'}, {'text': 'ethambutol', 'type': 'Chemical', 'start': 649, 'end': 659, 'mesh': 'D004977'}, {'text': 'EMB', 'type': 'Chemical', 'start': 661, 'end': 664, 'mesh': 'D004977'}, {'text': 'optic neuropathy', 'type': 'Disease', 'start': 674, 'end': 690, 'mesh': 'D009901'}, {'text': 'visual deficits', 'type': 'Disease', 'start': 731, 'end': 746, 'mesh': 'D014786'}, {'text': 'EMB', 'type': 'Chemical', 'start': 1312, 'end': 1315, 'mesh': 'D004977'}, {'text': 'optic neuropathy', 'type': 'Disease', 'start': 1324, 'end': 1340, 'mesh': 'D009901'}, {'text': 'visual deficits', 'type': 'Disease', 'start': 1527, 'end': 1542, 'mesh': 'D014786'}, {'text': 'visual deficits', 'type': 'Disease', 'start': 1578, 'end': 1593, 'mesh': 'D014786'}, {'text': 'visual deficits', 'type': 'Disease', 'start': 1909, 'end': 1924, 'mesh': 'D014786'}, {'text': 'EMB', 'type': 'Chemical', 'start': 2081, 'end': 2084, 'mesh': 'D004977'}, {'text': 'optic neuropathy', 'type': 'Disease', 'start': 2093, 'end': 2109, 'mesh': 'D009901'}, {'text': 'optic neuropathies', 'type': 'Disease', 'start': 2357, 'end': 2375, 'mesh': 'D009901'}, {'text': 'optic neuropathies', 'type': 'Disease', 'start': 2436, 'end': 2454, 'mesh': 'D009901'}, {'text': 'EMB', 'type': 'Chemical', 'start': 2496, 'end': 2499, 'mesh': 'D004977'}, {'text': 'optic neuropathy', 'type': 'Disease', 'start': 2508, 'end': 2524, 'mesh': 'D009901'}, {'text': 'ethambutol', 'type': 'Chemical', 'start': 2561, 'end': 2571, 'mesh': 'D004977'}, {'text': 'renal impairment', 'type': 'Disease', 'start': 2596, 'end': 2612, 'mesh': 'D051437'}]"
+566,15266215,Effects of the cyclooxygenase-2 specific inhibitor valdecoxib versus nonsteroidal antiinflammatory agents and placebo on cardiovascular thrombotic events in patients with arthritis.,"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 trials.","[{'text': 'valdecoxib', 'type': 'Chemical', 'start': 51, 'end': 61, 'mesh': 'C406224'}, {'text': 'thrombotic', 'type': 'Disease', 'start': 136, 'end': 146, 'mesh': 'D013927'}, {'text': 'arthritis', 'type': 'Disease', 'start': 171, 'end': 180, 'mesh': 'D001168'}, {'text': 'thrombotic', 'type': 'Disease', 'start': 239, 'end': 249, 'mesh': 'D013927'}, {'text': 'valdecoxib', 'type': 'Chemical', 'start': 426, 'end': 436, 'mesh': 'C406224'}, {'text': 'osteoarthritis', 'type': 'Disease', 'start': 505, 'end': 519, 'mesh': 'D010003'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 524, 'end': 544, 'mesh': 'D001172'}, {'text': 'thrombotic', 'type': 'Disease', 'start': 632, 'end': 642, 'mesh': 'D013927'}, {'text': 'thrombotic', 'type': 'Disease', 'start': 713, 'end': 723, 'mesh': 'D013927'}, {'text': 'valdecoxib', 'type': 'Chemical', 'start': 760, 'end': 770, 'mesh': 'C406224'}, {'text': 'diclofenac', 'type': 'Chemical', 'start': 809, 'end': 819, 'mesh': 'D004008'}, {'text': 'ibuprofen', 'type': 'Chemical', 'start': 831, 'end': 840, 'mesh': 'D007052'}, {'text': 'naproxen', 'type': 'Chemical', 'start': 856, 'end': 864, 'mesh': 'D009288'}, {'text': 'osteoarthritis', 'type': 'Disease', 'start': 913, 'end': 927, 'mesh': 'D010003'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 932, 'end': 952, 'mesh': 'D001172'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1113, 'end': 1120, 'mesh': 'D001241'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1148, 'end': 1155, 'mesh': 'D001241'}, {'text': 'thrombotic', 'type': 'Disease', 'start': 1210, 'end': 1220, 'mesh': 'D013927'}, {'text': 'valdecoxib', 'type': 'Chemical', 'start': 1245, 'end': 1255, 'mesh': 'C406224'}, {'text': 'thrombotic', 'type': 'Disease', 'start': 1298, 'end': 1308, 'mesh': 'D013927'}, {'text': 'valdecoxib', 'type': 'Chemical', 'start': 1342, 'end': 1352, 'mesh': 'C406224'}, {'text': 'Thrombotic', 'type': 'Disease', 'start': 1359, 'end': 1369, 'mesh': 'D013927'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1412, 'end': 1419, 'mesh': 'D001241'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1443, 'end': 1450, 'mesh': 'D001241'}, {'text': 'valdecoxib', 'type': 'Chemical', 'start': 1474, 'end': 1484, 'mesh': 'C406224'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1557, 'end': 1564, 'mesh': 'D001241'}, {'text': 'valdecoxib', 'type': 'Chemical', 'start': 1616, 'end': 1626, 'mesh': 'C406224'}, {'text': 'valdecoxib', 'type': 'Chemical', 'start': 1751, 'end': 1761, 'mesh': 'C406224'}, {'text': 'thrombotic', 'type': 'Disease', 'start': 1818, 'end': 1828, 'mesh': 'D013927'}, {'text': 'osteoarthritis', 'type': 'Disease', 'start': 1882, 'end': 1896, 'mesh': 'D010003'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 1901, 'end': 1921, 'mesh': 'D001172'}]"
+567,14742097,"A randomized, placebo-controlled, crossover study of ephedrine for SSRI-induced female sexual dysfunction.","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.","[{'text': 'ephedrine', 'type': 'Chemical', 'start': 53, 'end': 62, 'mesh': 'D004809'}, {'text': 'sexual dysfunction', 'type': 'Disease', 'start': 87, 'end': 105, 'mesh': 'D020018'}, {'text': 'ephedrine', 'type': 'Chemical', 'start': 160, 'end': 169, 'mesh': 'D004809'}, {'text': 'sexual dysfunction', 'type': 'Disease', 'start': 325, 'end': 343, 'mesh': 'D020018'}, {'text': 'sexually dysfunctional', 'type': 'Disease', 'start': 354, 'end': 376, 'mesh': 'D020018'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 400, 'end': 410, 'mesh': 'D005473'}, {'text': 'sertraline', 'type': 'Chemical', 'start': 412, 'end': 422, 'mesh': 'D020280'}, {'text': 'paroxetine', 'type': 'Chemical', 'start': 427, 'end': 437, 'mesh': 'D017374'}, {'text': 'ephedrine', 'type': 'Chemical', 'start': 538, 'end': 547, 'mesh': 'D004809'}, {'text': 'ephedrine', 'type': 'Chemical', 'start': 762, 'end': 771, 'mesh': 'D004809'}]"
+568,11890511,Erectile dysfunction occurs following substantia nigra lesions in the rat.,"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.","[{'text': 'Erectile dysfunction', 'type': 'Disease', 'start': 0, 'end': 20, 'mesh': 'D007172'}, {'text': '6-hydroxydopamine', 'type': 'Chemical', 'start': 157, 'end': 174, 'mesh': 'D016627'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 232, 'end': 243, 'mesh': 'D001058'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 540, 'end': 548, 'mesh': 'D004298'}, {'text': 'erectile dysfunction', 'type': 'Disease', 'start': 697, 'end': 717, 'mesh': 'D007172'}, {'text': 'erectile dysfunction', 'type': 'Disease', 'start': 760, 'end': 780, 'mesh': 'D007172'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 784, 'end': 803, 'mesh': 'D010300'}]"
+569,9270571,"Potential therapeutic use of the selective dopamine D1 receptor agonist, A-86929: an acute study in parkinsonian levodopa-primed monkeys.","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.","[{'text': 'dopamine', 'type': 'Chemical', 'start': 43, 'end': 51, 'mesh': 'D004298'}, {'text': 'A-86929', 'type': 'Chemical', 'start': 73, 'end': 80, 'mesh': 'C095427'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 100, 'end': 112, 'mesh': 'D020734'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 113, 'end': 121, 'mesh': 'D007980'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 162, 'end': 170, 'mesh': 'D004298'}, {'text': 'DA', 'type': 'Chemical', 'start': 172, 'end': 174, 'mesh': 'D004298'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 217, 'end': 236, 'mesh': 'D010300'}, {'text': 'PD', 'type': 'Disease', 'start': 238, 'end': 240, 'mesh': 'D010300'}, {'text': 'DA', 'type': 'Chemical', 'start': 293, 'end': 295, 'mesh': 'D004298'}, {'text': 'SKF-82958', 'type': 'Chemical', 'start': 325, 'end': 334, 'mesh': 'C071262'}, {'text': '6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzaze pine hydrobromide', 'type': 'Chemical', 'start': 336, 'end': 425, 'mesh': 'C071262'}, {'text': 'A-77636', 'type': 'Chemical', 'start': 431, 'end': 438, 'mesh': 'C079415'}, {'text': ""[1R, 3S] 3-[1'-admantyl]-1-aminomethyl-3,4-dihydro-5,6-dihydroxy-1H-2-benzo pyran hydrochloride"", 'type': 'Chemical', 'start': 440, 'end': 535, 'mesh': 'C079415'}, {'text': 'SKF-82958', 'type': 'Chemical', 'start': 611, 'end': 620, 'mesh': 'C071262'}, {'text': 'A-77636', 'type': 'Chemical', 'start': 647, 'end': 654, 'mesh': 'C079415'}, {'text': '1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine', 'type': 'Chemical', 'start': 768, 'end': 812, 'mesh': 'D015632'}, {'text': 'MPTP', 'type': 'Chemical', 'start': 814, 'end': 818, 'mesh': 'D015632'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 865, 'end': 873, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 882, 'end': 893, 'mesh': 'D004409'}, {'text': 'dyskinetic', 'type': 'Disease', 'start': 924, 'end': 934, 'mesh': 'D004409'}, {'text': 'A-86929', 'type': 'Chemical', 'start': 1000, 'end': 1007, 'mesh': 'C095427'}, {'text': '[-]-[5aR,11bS]-4,5,5a,6,7,11b-hexahydro-2-propyl-3-thia-5-+ ++azacyclopent-1- ena[c]phenathrene-9-10-diol', 'type': 'Chemical', 'start': 1009, 'end': 1114, 'mesh': 'C095427'}, {'text': 'DA', 'type': 'Chemical', 'start': 1138, 'end': 1140, 'mesh': 'D004298'}, {'text': 'Levodopa', 'type': 'Chemical', 'start': 1207, 'end': 1215, 'mesh': 'D007980'}, {'text': 'DA', 'type': 'Chemical', 'start': 1224, 'end': 1226, 'mesh': 'D004298'}, {'text': 'LY-171555', 'type': 'Chemical', 'start': 1253, 'end': 1262, 'mesh': 'C416545'}, {'text': '[4aR-trans]-4,4a,5,6,7,8,8a,9-o-dihydro-5n-propyl-2H-pyrazo lo-3-4-quinoline hydrochloride', 'type': 'Chemical', 'start': 1264, 'end': 1354, 'mesh': 'C416545'}, {'text': 'A-86929', 'type': 'Chemical', 'start': 1411, 'end': 1418, 'mesh': 'C095427'}, {'text': 'MPTP', 'type': 'Chemical', 'start': 1453, 'end': 1457, 'mesh': 'D015632'}, {'text': 'parkinsonism', 'type': 'Disease', 'start': 1466, 'end': 1478, 'mesh': 'D020734'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1482, 'end': 1490, 'mesh': 'D007980'}, {'text': 'LY-171555', 'type': 'Chemical', 'start': 1495, 'end': 1504, 'mesh': 'C416545'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1543, 'end': 1551, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 1560, 'end': 1571, 'mesh': 'D004409'}, {'text': 'LY-171555', 'type': 'Chemical', 'start': 1606, 'end': 1615, 'mesh': 'C416545'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1643, 'end': 1651, 'mesh': 'D007980'}, {'text': 'DA', 'type': 'Chemical', 'start': 1682, 'end': 1684, 'mesh': 'D004298'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1860, 'end': 1868, 'mesh': 'D007980'}, {'text': 'DA', 'type': 'Chemical', 'start': 1883, 'end': 1885, 'mesh': 'D004298'}, {'text': 'DA', 'type': 'Chemical', 'start': 1914, 'end': 1916, 'mesh': 'D004298'}, {'text': 'A-86929', 'type': 'Chemical', 'start': 1986, 'end': 1993, 'mesh': 'C095427'}, {'text': 'PD', 'type': 'Disease', 'start': 2073, 'end': 2075, 'mesh': 'D010300'}]"
+570,7189975,Deaths from local anesthetic-induced convulsions in mice.,"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.","[{'text': 'convulsions', 'type': 'Disease', 'start': 37, 'end': 48, 'mesh': 'D012640'}, {'text': 'convulsions', 'type': 'Disease', 'start': 245, 'end': 256, 'mesh': 'D012640'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 320, 'end': 331, 'mesh': 'D002045'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 359, 'end': 368, 'mesh': 'D008012'}, {'text': 'chloroprocaine', 'type': 'Chemical', 'start': 400, 'end': 414, 'mesh': 'C004616'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 446, 'end': 457, 'mesh': 'D002045'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 496, 'end': 505, 'mesh': 'D008012'}, {'text': 'chloroprocaine', 'type': 'Chemical', 'start': 533, 'end': 547, 'mesh': 'C004616'}, {'text': 'Convulsions', 'type': 'Disease', 'start': 549, 'end': 560, 'mesh': 'D012640'}, {'text': 'cardiopulmonary arrest', 'type': 'Disease', 'start': 609, 'end': 631, 'mesh': 'D006323'}, {'text': 'convulsions', 'type': 'Disease', 'start': 693, 'end': 704, 'mesh': 'D012640'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 741, 'end': 752, 'mesh': 'D002045'}, {'text': 'seizures', 'type': 'Disease', 'start': 761, 'end': 769, 'mesh': 'D012640'}, {'text': 'chloroprocaine', 'type': 'Chemical', 'start': 785, 'end': 799, 'mesh': 'C004616'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 824, 'end': 833, 'mesh': 'D008012'}, {'text': 'convulsions', 'type': 'Disease', 'start': 938, 'end': 949, 'mesh': 'D012640'}]"
+571,6415512,"Myoclonic, atonic, and absence seizures following institution of carbamazepine therapy in children.","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.","[{'text': 'carbamazepine', 'type': 'Chemical', 'start': 65, 'end': 78, 'mesh': 'D002220'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 148, 'end': 161, 'mesh': 'D002220'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 166, 'end': 174, 'mesh': 'D004827'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 330, 'end': 343, 'mesh': 'D002220'}, {'text': 'seizures', 'type': 'Disease', 'start': 451, 'end': 459, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 503, 'end': 511, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 543, 'end': 551, 'mesh': 'D012640'}, {'text': 'ceroid lipofuscinosis', 'type': 'Disease', 'start': 586, 'end': 607, 'mesh': 'D009472'}]"
+572,1928887,Naloxone reversal of hypotension due to captopril overdose.,"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.","[{'text': 'Naloxone', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D009270'}, {'text': 'hypotension', 'type': 'Disease', 'start': 21, 'end': 32, 'mesh': 'D007022'}, {'text': 'captopril', 'type': 'Chemical', 'start': 40, 'end': 49, 'mesh': 'D002216'}, {'text': 'overdose', 'type': 'Disease', 'start': 50, 'end': 58, 'mesh': 'D062787'}, {'text': 'captopril', 'type': 'Chemical', 'start': 87, 'end': 96, 'mesh': 'D002216'}, {'text': 'angiotensin-converting enzyme inhibitors', 'type': 'Chemical', 'start': 107, 'end': 147, 'mesh': 'D000806'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 219, 'end': 227, 'mesh': 'D009270'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 267, 'end': 278, 'mesh': 'D007022'}, {'text': 'captopril', 'type': 'Chemical', 'start': 290, 'end': 299, 'mesh': 'D002216'}, {'text': 'captopril', 'type': 'Chemical', 'start': 336, 'end': 345, 'mesh': 'D002216'}, {'text': 'overdose', 'type': 'Disease', 'start': 346, 'end': 354, 'mesh': 'D062787'}, {'text': 'hypotension', 'type': 'Disease', 'start': 377, 'end': 388, 'mesh': 'D007022'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 440, 'end': 448, 'mesh': 'D009270'}, {'text': 'captopril', 'type': 'Chemical', 'start': 503, 'end': 512, 'mesh': 'D002216'}, {'text': 'hypotension', 'type': 'Disease', 'start': 521, 'end': 532, 'mesh': 'D007022'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 546, 'end': 554, 'mesh': 'D009270'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 603, 'end': 611, 'mesh': 'D009270'}, {'text': 'hypotension', 'type': 'Disease', 'start': 631, 'end': 642, 'mesh': 'D007022'}, {'text': 'captopril', 'type': 'Chemical', 'start': 658, 'end': 667, 'mesh': 'D002216'}]"
+573,1728915,Carbamazepine-induced cardiac dysfunction. Characterization of two distinct clinical syndromes.,"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.","[{'text': 'Carbamazepine', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'D002220'}, {'text': 'cardiac dysfunction', 'type': 'Disease', 'start': 22, 'end': 41, 'mesh': 'D006331'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 117, 'end': 128, 'mesh': 'D001919'}, {'text': 'atrioventricular block', 'type': 'Disease', 'start': 133, 'end': 155, 'mesh': 'D054537'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 168, 'end': 181, 'mesh': 'D002220'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 313, 'end': 326, 'mesh': 'D002220'}, {'text': 'cardiac dysfunction', 'type': 'Disease', 'start': 338, 'end': 357, 'mesh': 'D006331'}, {'text': 'sinus tachycardias', 'type': 'Disease', 'start': 395, 'end': 413, 'mesh': 'D013616'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 442, 'end': 455, 'mesh': 'D002220'}, {'text': 'overdose', 'type': 'Disease', 'start': 456, 'end': 464, 'mesh': 'D062787'}, {'text': 'bradyarrhythmias', 'type': 'Disease', 'start': 572, 'end': 588, 'mesh': 'D001919'}, {'text': 'atrioventricular conduction delay', 'type': 'Disease', 'start': 592, 'end': 625, 'mesh': 'D054537'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 683, 'end': 696, 'mesh': 'D002220'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 719, 'end': 732, 'mesh': 'D002220'}, {'text': 'psychiatric', 'type': 'Disease', 'start': 788, 'end': 799, 'mesh': 'D001523'}]"
+574,20558148,Glutamatergic neurotransmission mediated by NMDA receptors in the inferior colliculus can modulate haloperidol-induced catalepsy.,"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.","[{'text': 'NMDA', 'type': 'Chemical', 'start': 44, 'end': 48, 'mesh': 'D016202'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 99, 'end': 110, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 119, 'end': 128, 'mesh': 'D002375'}, {'text': 'amino acid', 'type': 'Chemical', 'start': 501, 'end': 511, 'mesh': 'D000596'}, {'text': 'amino acid', 'type': 'Chemical', 'start': 694, 'end': 704, 'mesh': 'D000596'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 742, 'end': 751, 'mesh': 'D002375'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 767, 'end': 775, 'mesh': 'D004298'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 793, 'end': 804, 'mesh': 'D006220'}, {'text': 'Haloperidol', 'type': 'Chemical', 'start': 857, 'end': 868, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 877, 'end': 886, 'mesh': 'D002375'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 948, 'end': 957, 'mesh': 'D018698'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 958, 'end': 962, 'mesh': 'D016202'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 985, 'end': 991, 'mesh': 'D016291'}, {'text': 'AP7', 'type': 'Chemical', 'start': 1023, 'end': 1026, 'mesh': 'C031231'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 1065, 'end': 1069, 'mesh': 'D016202'}, {'text': 'N-methyl-d-aspartate', 'type': 'Chemical', 'start': 1087, 'end': 1107, 'mesh': 'D016202'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 1109, 'end': 1113, 'mesh': 'D016202'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 1200, 'end': 1206, 'mesh': 'D016291'}, {'text': 'AP7', 'type': 'Chemical', 'start': 1211, 'end': 1214, 'mesh': 'C031231'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1250, 'end': 1261, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 1291, 'end': 1300, 'mesh': 'D002375'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 1419, 'end': 1423, 'mesh': 'D016202'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 1496, 'end': 1505, 'mesh': 'D018698'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1575, 'end': 1586, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 1595, 'end': 1604, 'mesh': 'D002375'}]"
+575,19940105,Metabotropic glutamate 7 receptor subtype modulates motor symptoms in rodent models of Parkinson's disease.,"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.","[{'text': 'glutamate', 'type': 'Chemical', 'start': 13, 'end': 22, 'mesh': 'D018698'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 87, 'end': 106, 'mesh': 'D010300'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 121, 'end': 130, 'mesh': 'D018698'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 282, 'end': 301, 'mesh': 'D010300'}, {'text': 'PD', 'type': 'Disease', 'start': 303, 'end': 305, 'mesh': 'D010300'}, {'text': 'PD', 'type': 'Disease', 'start': 471, 'end': 473, 'mesh': 'D010300'}, {'text': ""N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride"", 'type': 'Chemical', 'start': 503, 'end': 554, 'mesh': 'C507346'}, {'text': 'AMN082', 'type': 'Chemical', 'start': 556, 'end': 562, 'mesh': 'C507346'}, {'text': 'PD', 'type': 'Disease', 'start': 673, 'end': 675, 'mesh': 'D010300'}, {'text': 'AMN082', 'type': 'Chemical', 'start': 765, 'end': 771, 'mesh': 'C507346'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 781, 'end': 792, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 801, 'end': 810, 'mesh': 'D002375'}, {'text': 'AMN082', 'type': 'Chemical', 'start': 820, 'end': 826, 'mesh': 'C507346'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 853, 'end': 864, 'mesh': 'D001058'}, {'text': '6-hydroxydopamine', 'type': 'Chemical', 'start': 897, 'end': 914, 'mesh': 'D016627'}, {'text': '6-OHDA', 'type': 'Chemical', 'start': 916, 'end': 922, 'mesh': 'D016627'}, {'text': 'akinetic', 'type': 'Disease', 'start': 994, 'end': 1002, 'mesh': 'D018476'}, {'text': 'PD', 'type': 'Disease', 'start': 1015, 'end': 1017, 'mesh': 'D010300'}, {'text': 'AMN082', 'type': 'Chemical', 'start': 1036, 'end': 1042, 'mesh': 'C507346'}, {'text': '6-OHDA', 'type': 'Chemical', 'start': 1113, 'end': 1119, 'mesh': 'D016627'}, {'text': 'AMN082', 'type': 'Chemical', 'start': 1148, 'end': 1154, 'mesh': 'C507346'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1179, 'end': 1190, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 1199, 'end': 1208, 'mesh': 'D002375'}, {'text': 'AMN082', 'type': 'Chemical', 'start': 1313, 'end': 1319, 'mesh': 'C507346'}, {'text': 'PD', 'type': 'Disease', 'start': 1380, 'end': 1382, 'mesh': 'D010300'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1500, 'end': 1508, 'mesh': 'D004298'}]"
+576,19923525,Nimodipine prevents memory impairment caused by nitroglycerin-induced hypotension in adult mice.,"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.","[{'text': 'Nimodipine', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D009553'}, {'text': 'memory impairment', 'type': 'Disease', 'start': 20, 'end': 37, 'mesh': 'D008569'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 48, 'end': 61, 'mesh': 'D005996'}, {'text': 'hypotension', 'type': 'Disease', 'start': 70, 'end': 81, 'mesh': 'D007022'}, {'text': 'Hypotension', 'type': 'Disease', 'start': 109, 'end': 120, 'mesh': 'D007022'}, {'text': 'cognitive dysfunction', 'type': 'Disease', 'start': 212, 'end': 233, 'mesh': 'D003072'}, {'text': 'nimodipine', 'type': 'Chemical', 'start': 265, 'end': 275, 'mesh': 'D009553'}, {'text': 'NIMO', 'type': 'Chemical', 'start': 277, 'end': 281, 'mesh': 'D009553'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 312, 'end': 325, 'mesh': 'D005996'}, {'text': 'NTG', 'type': 'Chemical', 'start': 327, 'end': 330, 'mesh': 'D005996'}, {'text': 'hypotension', 'type': 'Disease', 'start': 340, 'end': 351, 'mesh': 'D007022'}, {'text': 'NTG', 'type': 'Chemical', 'start': 790, 'end': 793, 'mesh': 'D005996'}, {'text': 'NTG', 'type': 'Chemical', 'start': 825, 'end': 828, 'mesh': 'D005996'}, {'text': 'NTG', 'type': 'Chemical', 'start': 852, 'end': 855, 'mesh': 'D005996'}, {'text': 'NIMO', 'type': 'Chemical', 'start': 860, 'end': 864, 'mesh': 'D009553'}, {'text': 'NIMO', 'type': 'Chemical', 'start': 885, 'end': 889, 'mesh': 'D009553'}, {'text': 'hypotension', 'type': 'Disease', 'start': 911, 'end': 922, 'mesh': 'D007022'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 1138, 'end': 1149, 'mesh': 'D007022'}, {'text': 'NTG', 'type': 'Chemical', 'start': 1263, 'end': 1266, 'mesh': 'D005996'}, {'text': 'NIMO', 'type': 'Chemical', 'start': 1269, 'end': 1273, 'mesh': 'D009553'}, {'text': 'NTG', 'type': 'Chemical', 'start': 1286, 'end': 1289, 'mesh': 'D005996'}, {'text': 'NTG', 'type': 'Chemical', 'start': 1567, 'end': 1570, 'mesh': 'D005996'}, {'text': 'NTG', 'type': 'Chemical', 'start': 1583, 'end': 1586, 'mesh': 'D005996'}, {'text': 'NIMO', 'type': 'Chemical', 'start': 1589, 'end': 1593, 'mesh': 'D009553'}, {'text': 'NIMO', 'type': 'Chemical', 'start': 1827, 'end': 1831, 'mesh': 'D009553'}, {'text': 'NTG', 'type': 'Chemical', 'start': 2042, 'end': 2045, 'mesh': 'D005996'}, {'text': 'NTG', 'type': 'Chemical', 'start': 2117, 'end': 2120, 'mesh': 'D005996'}, {'text': 'NIMO', 'type': 'Chemical', 'start': 2123, 'end': 2127, 'mesh': 'D009553'}, {'text': 'NTG', 'type': 'Chemical', 'start': 2259, 'end': 2262, 'mesh': 'D005996'}, {'text': 'hypotension', 'type': 'Disease', 'start': 2389, 'end': 2400, 'mesh': 'D007022'}, {'text': 'NIMO', 'type': 'Chemical', 'start': 2416, 'end': 2420, 'mesh': 'D009553'}, {'text': 'NTG', 'type': 'Chemical', 'start': 2494, 'end': 2497, 'mesh': 'D005996'}, {'text': 'hypotension', 'type': 'Disease', 'start': 2544, 'end': 2555, 'mesh': 'D007022'}, {'text': 'NIMO', 'type': 'Chemical', 'start': 2580, 'end': 2584, 'mesh': 'D009553'}, {'text': 'calcium', 'type': 'Chemical', 'start': 2635, 'end': 2642, 'mesh': 'D002118'}, {'text': 'hypotension', 'type': 'Disease', 'start': 2662, 'end': 2673, 'mesh': 'D007022'}]"
+577,19058474,Fatal haemopericardium and gastrointestinal haemorrhage due to possible interaction of cranberry juice with warfarin.,"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.","[{'text': 'haemopericardium', 'type': 'Disease', 'start': 6, 'end': 22, 'mesh': 'D010490'}, {'text': 'gastrointestinal haemorrhage', 'type': 'Disease', 'start': 27, 'end': 55, 'mesh': 'D006471'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 108, 'end': 116, 'mesh': 'D014859'}, {'text': 'haemorrhage', 'type': 'Disease', 'start': 153, 'end': 164, 'mesh': 'D006470'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 269, 'end': 277, 'mesh': 'D014859'}, {'text': 'flavonoids', 'type': 'Chemical', 'start': 333, 'end': 343, 'mesh': 'D005419'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 408, 'end': 416, 'mesh': 'D014859'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 471, 'end': 479, 'mesh': 'D014859'}]"
+578,18808529,Isoproterenol induces primary loss of dystrophin in rat hearts: correlation with myocardial injury.,"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.","[{'text': 'Isoproterenol', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'D007545'}, {'text': 'myocardial injury', 'type': 'Disease', 'start': 81, 'end': 98, 'mesh': 'D009202'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 117, 'end': 130, 'mesh': 'D007545'}, {'text': 'myocardial damage', 'type': 'Disease', 'start': 139, 'end': 156, 'mesh': 'D009202'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 187, 'end': 193, 'mesh': 'D010100'}, {'text': 'hypotension', 'type': 'Disease', 'start': 231, 'end': 242, 'mesh': 'D007022'}, {'text': 'myocardial hyperactivity', 'type': 'Disease', 'start': 247, 'end': 271, 'mesh': 'D009202'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 470, 'end': 483, 'mesh': 'D007545'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 732, 'end': 745, 'mesh': 'D007545'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 876, 'end': 889, 'mesh': 'D007545'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1433, 'end': 1446, 'mesh': 'D007545'}, {'text': 'ischaemic injury', 'type': 'Disease', 'start': 1665, 'end': 1681, 'mesh': 'D007511'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1830, 'end': 1843, 'mesh': 'D007545'}]"
+579,18674790,High fat diet-fed obese rats are highly sensitive to doxorubicin-induced cardiotoxicity.,"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.","[{'text': 'fat', 'type': 'Chemical', 'start': 5, 'end': 8, 'mesh': 'D004041'}, {'text': 'obese', 'type': 'Disease', 'start': 18, 'end': 23, 'mesh': 'D009765'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 53, 'end': 64, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 73, 'end': 87, 'mesh': 'D066126'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 112, 'end': 123, 'mesh': 'D004317'}, {'text': 'Adriamycin', 'type': 'Chemical', 'start': 125, 'end': 135, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 172, 'end': 186, 'mesh': 'D066126'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 306, 'end': 317, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 326, 'end': 340, 'mesh': 'D066126'}, {'text': 'triglycerides', 'type': 'Chemical', 'start': 421, 'end': 434, 'mesh': 'D014280'}, {'text': 'ATP', 'type': 'Chemical', 'start': 479, 'end': 482, 'mesh': 'D000255'}, {'text': 'fat', 'type': 'Chemical', 'start': 624, 'end': 627, 'mesh': 'D004041'}, {'text': 'obesity', 'type': 'Disease', 'start': 654, 'end': 661, 'mesh': 'D009765'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 717, 'end': 728, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 737, 'end': 751, 'mesh': 'D066126'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 773, 'end': 784, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 857, 'end': 871, 'mesh': 'D066126'}, {'text': 'cardiac dysfunction', 'type': 'Disease', 'start': 873, 'end': 892, 'mesh': 'D006331'}, {'text': 'obese', 'type': 'Disease', 'start': 939, 'end': 944, 'mesh': 'D009765'}, {'text': 'OB', 'type': 'Disease', 'start': 946, 'end': 948, 'mesh': 'D009765'}, {'text': 'Doxorubicin', 'type': 'Chemical', 'start': 1016, 'end': 1027, 'mesh': 'D004317'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1089, 'end': 1100, 'mesh': 'D004317'}, {'text': 'doxorubicinol', 'type': 'Chemical', 'start': 1105, 'end': 1118, 'mesh': 'C010013'}, {'text': 'OB', 'type': 'Disease', 'start': 1170, 'end': 1172, 'mesh': 'D009765'}, {'text': 'OB', 'type': 'Disease', 'start': 1215, 'end': 1217, 'mesh': 'D009765'}, {'text': 'OB', 'type': 'Disease', 'start': 1573, 'end': 1575, 'mesh': 'D009765'}, {'text': 'AMP', 'type': 'Chemical', 'start': 1606, 'end': 1609, 'mesh': 'D000249'}, {'text': 'ATP', 'type': 'Chemical', 'start': 1661, 'end': 1664, 'mesh': 'D000255'}, {'text': 'ATP', 'type': 'Chemical', 'start': 1697, 'end': 1700, 'mesh': 'D000255'}, {'text': 'ADP', 'type': 'Chemical', 'start': 1701, 'end': 1704, 'mesh': 'D000244'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1717, 'end': 1728, 'mesh': 'D004317'}, {'text': 'obese', 'type': 'Disease', 'start': 1887, 'end': 1892, 'mesh': 'D009765'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1923, 'end': 1934, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1943, 'end': 1957, 'mesh': 'D066126'}, {'text': 'ATP', 'type': 'Chemical', 'start': 2012, 'end': 2015, 'mesh': 'D000255'}]"
+580,18441470,Complete atrioventricular block secondary to lithium therapy.,"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.","[{'text': 'atrioventricular block', 'type': 'Disease', 'start': 9, 'end': 31, 'mesh': 'D054537'}, {'text': 'lithium', 'type': 'Chemical', 'start': 45, 'end': 52, 'mesh': 'D008094'}, {'text': 'Sinus node dysfunction', 'type': 'Disease', 'start': 62, 'end': 84, 'mesh': 'D012804'}, {'text': 'lithium', 'type': 'Chemical', 'start': 163, 'end': 170, 'mesh': 'D008094'}, {'text': 'atrioventricular (AV) block', 'type': 'Disease', 'start': 202, 'end': 229, 'mesh': 'D054537'}, {'text': 'syncopal attacks', 'type': 'Disease', 'start': 235, 'end': 251, 'mesh': 'D013575'}, {'text': 'lithium', 'type': 'Chemical', 'start': 275, 'end': 282, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 346, 'end': 353, 'mesh': 'D008094'}, {'text': 'syncopal attacks', 'type': 'Disease', 'start': 419, 'end': 435, 'mesh': 'D013575'}, {'text': 'Lithium', 'type': 'Chemical', 'start': 437, 'end': 444, 'mesh': 'D008094'}]"
+581,17366349,Neuroleptic malignant syndrome induced by ziprasidone on the second day of treatment.,"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.","[{'text': 'Neuroleptic malignant syndrome', 'type': 'Disease', 'start': 0, 'end': 30, 'mesh': 'D009459'}, {'text': 'ziprasidone', 'type': 'Chemical', 'start': 42, 'end': 53, 'mesh': 'C092292'}, {'text': 'Neuroleptic malignant syndrome', 'type': 'Disease', 'start': 86, 'end': 116, 'mesh': 'D009459'}, {'text': 'NMS', 'type': 'Disease', 'start': 118, 'end': 121, 'mesh': 'D009459'}, {'text': 'movement disorders', 'type': 'Disease', 'start': 181, 'end': 199, 'mesh': 'D009069'}, {'text': 'neuroleptic malignant syndrome', 'type': 'Disease', 'start': 223, 'end': 253, 'mesh': 'D009459'}, {'text': 'NMS', 'type': 'Disease', 'start': 255, 'end': 258, 'mesh': 'D009459'}, {'text': 'ziprasidone', 'type': 'Chemical', 'start': 287, 'end': 298, 'mesh': 'C092292'}, {'text': 'NMS', 'type': 'Disease', 'start': 371, 'end': 374, 'mesh': 'D009459'}, {'text': 'ziprasidone', 'type': 'Chemical', 'start': 410, 'end': 421, 'mesh': 'C092292'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 495, 'end': 508, 'mesh': 'D012559'}, {'text': 'NMS', 'type': 'Disease', 'start': 545, 'end': 548, 'mesh': 'D009459'}, {'text': 'ziprasidone', 'type': 'Chemical', 'start': 622, 'end': 633, 'mesh': 'C092292'}, {'text': 'NMS', 'type': 'Disease', 'start': 687, 'end': 690, 'mesh': 'D009459'}, {'text': 'ziprasidone', 'type': 'Chemical', 'start': 698, 'end': 709, 'mesh': 'C092292'}]"
+582,16584858,Role of mangiferin on biochemical alterations and antioxidant status in isoproterenol-induced myocardial infarction in rats.,"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.","[{'text': 'mangiferin', 'type': 'Chemical', 'start': 8, 'end': 18, 'mesh': 'C013592'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 72, 'end': 85, 'mesh': 'D007545'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 94, 'end': 115, 'mesh': 'D009203'}, {'text': 'mangiferin', 'type': 'Chemical', 'start': 177, 'end': 187, 'mesh': 'C013592'}, {'text': 'polyphenol', 'type': 'Chemical', 'start': 191, 'end': 201, 'mesh': 'D059808'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 250, 'end': 263, 'mesh': 'D007545'}, {'text': 'ISPH', 'type': 'Chemical', 'start': 265, 'end': 269, 'mesh': 'D007545'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 279, 'end': 300, 'mesh': 'D009203'}, {'text': 'MI', 'type': 'Disease', 'start': 302, 'end': 304, 'mesh': 'D009203'}, {'text': 'ISPH', 'type': 'Chemical', 'start': 377, 'end': 381, 'mesh': 'D007545'}, {'text': 'myocardial damage', 'type': 'Disease', 'start': 459, 'end': 476, 'mesh': 'D009202'}, {'text': 'lactate', 'type': 'Chemical', 'start': 547, 'end': 554, 'mesh': 'D019344'}, {'text': 'creatine', 'type': 'Chemical', 'start': 579, 'end': 587, 'mesh': 'D003401'}, {'text': 'uric acid', 'type': 'Chemical', 'start': 632, 'end': 641, 'mesh': 'D014527'}, {'text': 'iron', 'type': 'Chemical', 'start': 667, 'end': 671, 'mesh': 'D007501'}, {'text': 'mangiferin', 'type': 'Chemical', 'start': 713, 'end': 723, 'mesh': 'C013592'}, {'text': 'triphenyl tetrazolium chloride', 'type': 'Chemical', 'start': 740, 'end': 770, 'mesh': 'C009591'}, {'text': 'TTC', 'type': 'Chemical', 'start': 772, 'end': 775, 'mesh': 'C009591'}, {'text': 'ischemic myocardium', 'type': 'Disease', 'start': 831, 'end': 850, 'mesh': 'D017202'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 897, 'end': 907, 'mesh': 'D013481'}, {'text': 'glutathione', 'type': 'Chemical', 'start': 929, 'end': 940, 'mesh': 'D005978'}, {'text': 'glutathione', 'type': 'Chemical', 'start': 953, 'end': 964, 'mesh': 'D005978'}, {'text': 'glutathione', 'type': 'Chemical', 'start': 981, 'end': 992, 'mesh': 'D005978'}, {'text': 'Vitamin C', 'type': 'Chemical', 'start': 1064, 'end': 1073, 'mesh': 'D001205'}, {'text': 'Vitamin E', 'type': 'Chemical', 'start': 1075, 'end': 1084, 'mesh': 'D014810'}, {'text': 'glutathione', 'type': 'Chemical', 'start': 1089, 'end': 1100, 'mesh': 'D005978'}, {'text': 'MI', 'type': 'Disease', 'start': 1124, 'end': 1126, 'mesh': 'D009203'}, {'text': 'mangiferin', 'type': 'Chemical', 'start': 1156, 'end': 1166, 'mesh': 'C013592'}, {'text': 'dimethyl sulphoxide', 'type': 'Chemical', 'start': 1211, 'end': 1230, 'mesh': 'D004121'}, {'text': 'MI', 'type': 'Disease', 'start': 1271, 'end': 1273, 'mesh': 'D009203'}, {'text': 'mangiferin', 'type': 'Chemical', 'start': 1466, 'end': 1476, 'mesh': 'C013592'}, {'text': 'ISPH', 'type': 'Chemical', 'start': 1507, 'end': 1511, 'mesh': 'D007545'}, {'text': 'MI', 'type': 'Disease', 'start': 1520, 'end': 1522, 'mesh': 'D009203'}, {'text': 'mangiferin', 'type': 'Chemical', 'start': 1573, 'end': 1583, 'mesh': 'C013592'}, {'text': 'ISPH', 'type': 'Chemical', 'start': 1619, 'end': 1623, 'mesh': 'D007545'}, {'text': 'MI', 'type': 'Disease', 'start': 1632, 'end': 1634, 'mesh': 'D009203'}, {'text': 'cardiac damage', 'type': 'Disease', 'start': 1720, 'end': 1734, 'mesh': 'D006331'}]"
+583,16563323,Remifentanil pretreatment reduces myoclonus after etomidate.,"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.","[{'text': 'Remifentanil', 'type': 'Chemical', 'start': 0, 'end': 12, 'mesh': 'C071741'}, {'text': 'myoclonus', 'type': 'Disease', 'start': 34, 'end': 43, 'mesh': 'D009207'}, {'text': 'etomidate', 'type': 'Chemical', 'start': 50, 'end': 59, 'mesh': 'D005045'}, {'text': 'remifentanil', 'type': 'Chemical', 'start': 146, 'end': 158, 'mesh': 'C071741'}, {'text': 'myoclonus', 'type': 'Disease', 'start': 216, 'end': 225, 'mesh': 'D009207'}, {'text': 'etomidate', 'type': 'Chemical', 'start': 258, 'end': 267, 'mesh': 'D005045'}, {'text': 'remifentanil', 'type': 'Chemical', 'start': 464, 'end': 476, 'mesh': 'C071741'}, {'text': 'remifentanil', 'type': 'Chemical', 'start': 519, 'end': 531, 'mesh': 'C071741'}, {'text': 'etomidate', 'type': 'Chemical', 'start': 554, 'end': 563, 'mesh': 'D005045'}, {'text': 'Myoclonus', 'type': 'Disease', 'start': 599, 'end': 608, 'mesh': 'D009207'}, {'text': 'nausea', 'type': 'Disease', 'start': 700, 'end': 706, 'mesh': 'D009325'}, {'text': 'pruritus', 'type': 'Disease', 'start': 708, 'end': 716, 'mesh': 'D011537'}, {'text': 'apnea', 'type': 'Disease', 'start': 722, 'end': 727, 'mesh': 'D001049'}, {'text': 'myoclonus', 'type': 'Disease', 'start': 804, 'end': 813, 'mesh': 'D009207'}, {'text': 'remifentanil', 'type': 'Chemical', 'start': 845, 'end': 857, 'mesh': 'C071741'}, {'text': 'apnea', 'type': 'Disease', 'start': 959, 'end': 964, 'mesh': 'D001049'}, {'text': 'nausea', 'type': 'Disease', 'start': 966, 'end': 972, 'mesh': 'D009325'}, {'text': 'pruritus', 'type': 'Disease', 'start': 977, 'end': 985, 'mesh': 'D011537'}, {'text': 'myoclonus', 'type': 'Disease', 'start': 1111, 'end': 1120, 'mesh': 'D009207'}, {'text': 'etomidate', 'type': 'Chemical', 'start': 1127, 'end': 1136, 'mesh': 'D005045'}, {'text': 'remifentanil', 'type': 'Chemical', 'start': 1183, 'end': 1195, 'mesh': 'C071741'}, {'text': 'myoclonus', 'type': 'Disease', 'start': 1216, 'end': 1225, 'mesh': 'D009207'}, {'text': 'etomidate', 'type': 'Chemical', 'start': 1232, 'end': 1241, 'mesh': 'D005045'}, {'text': 'apnea', 'type': 'Disease', 'start': 1291, 'end': 1296, 'mesh': 'D001049'}, {'text': 'nausea', 'type': 'Disease', 'start': 1298, 'end': 1304, 'mesh': 'D009325'}, {'text': 'pruritus', 'type': 'Disease', 'start': 1309, 'end': 1317, 'mesh': 'D011537'}, {'text': 'myoclonus', 'type': 'Disease', 'start': 1357, 'end': 1366, 'mesh': 'D009207'}, {'text': 'etomidate', 'type': 'Chemical', 'start': 1384, 'end': 1393, 'mesh': 'D005045'}]"
+584,16428827,Daidzein activates choline acetyltransferase from MC-IXC cells and improves drug-induced amnesia.,"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.","[{'text': 'Daidzein', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'C004742'}, {'text': 'choline', 'type': 'Chemical', 'start': 19, 'end': 26, 'mesh': 'D002794'}, {'text': 'amnesia', 'type': 'Disease', 'start': 89, 'end': 96, 'mesh': 'D000647'}, {'text': 'choline', 'type': 'Chemical', 'start': 102, 'end': 109, 'mesh': 'D002794'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 237, 'end': 250, 'mesh': 'D000109'}, {'text': 'ACh', 'type': 'Chemical', 'start': 252, 'end': 255, 'mesh': 'D000109'}, {'text': ""Alzheimer's disease"", 'type': 'Disease', 'start': 301, 'end': 320, 'mesh': 'D000544'}, {'text': 'AD', 'type': 'Disease', 'start': 322, 'end': 324, 'mesh': 'D000544'}, {'text': 'daidzein', 'type': 'Chemical', 'start': 534, 'end': 542, 'mesh': 'C004742'}, {'text': ""4',7-dihydroxy-isoflavone"", 'type': 'Chemical', 'start': 544, 'end': 569, 'mesh': 'C004742'}, {'text': 'daidzein', 'type': 'Chemical', 'start': 611, 'end': 619, 'mesh': 'C004742'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 650, 'end': 661, 'mesh': 'D012601'}, {'text': 'daidzein', 'type': 'Chemical', 'start': 764, 'end': 772, 'mesh': 'C004742'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 840, 'end': 851, 'mesh': 'D012601'}, {'text': 'amnesia', 'type': 'Disease', 'start': 860, 'end': 867, 'mesh': 'D000647'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 926, 'end': 937, 'mesh': 'D012601'}, {'text': 'daidzein', 'type': 'Chemical', 'start': 1078, 'end': 1086, 'mesh': 'C004742'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 1100, 'end': 1111, 'mesh': 'D012601'}, {'text': 'daidzein', 'type': 'Chemical', 'start': 1271, 'end': 1279, 'mesh': 'C004742'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 1301, 'end': 1314, 'mesh': 'D000109'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 1378, 'end': 1389, 'mesh': 'D012601'}, {'text': 'amnesia', 'type': 'Disease', 'start': 1398, 'end': 1405, 'mesh': 'D000647'}]"
+585,15985056,Possible azithromycin-associated hiccups.,"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.","[{'text': 'azithromycin', 'type': 'Chemical', 'start': 9, 'end': 21, 'mesh': 'D017963'}, {'text': 'hiccups', 'type': 'Disease', 'start': 33, 'end': 40, 'mesh': 'D006606'}, {'text': 'hiccups', 'type': 'Disease', 'start': 84, 'end': 91, 'mesh': 'D006606'}, {'text': 'azithromycin', 'type': 'Chemical', 'start': 106, 'end': 118, 'mesh': 'D017963'}, {'text': 'hiccups', 'type': 'Disease', 'start': 186, 'end': 193, 'mesh': 'D006606'}, {'text': 'azithromycin', 'type': 'Chemical', 'start': 210, 'end': 222, 'mesh': 'D017963'}, {'text': 'pharyngitis', 'type': 'Disease', 'start': 244, 'end': 255, 'mesh': 'D010612'}, {'text': 'Hiccups', 'type': 'Disease', 'start': 257, 'end': 264, 'mesh': 'D006606'}, {'text': 'azithromycin', 'type': 'Chemical', 'start': 316, 'end': 328, 'mesh': 'D017963'}, {'text': 'baclofen', 'type': 'Chemical', 'start': 346, 'end': 354, 'mesh': 'D001418'}, {'text': 'hiccups', 'type': 'Disease', 'start': 372, 'end': 379, 'mesh': 'D006606'}, {'text': 'hiccups', 'type': 'Disease', 'start': 401, 'end': 408, 'mesh': 'D006606'}, {'text': 'hiccups', 'type': 'Disease', 'start': 533, 'end': 540, 'mesh': 'D006606'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 559, 'end': 572, 'mesh': 'D003907'}, {'text': 'methylprednisolone', 'type': 'Chemical', 'start': 577, 'end': 595, 'mesh': 'D008775'}, {'text': 'benzodiazepines', 'type': 'Chemical', 'start': 598, 'end': 613, 'mesh': 'D001569'}, {'text': 'midazolam', 'type': 'Chemical', 'start': 615, 'end': 624, 'mesh': 'D008874'}, {'text': 'hiccups', 'type': 'Disease', 'start': 768, 'end': 775, 'mesh': 'D006606'}, {'text': 'hiccups', 'type': 'Disease', 'start': 803, 'end': 810, 'mesh': 'D006606'}, {'text': 'macrolide', 'type': 'Chemical', 'start': 841, 'end': 850, 'mesh': 'D018942'}, {'text': 'macrolides', 'type': 'Chemical', 'start': 1080, 'end': 1090, 'mesh': 'D018942'}, {'text': 'hiccups', 'type': 'Disease', 'start': 1142, 'end': 1149, 'mesh': 'D006606'}, {'text': 'azithromycin', 'type': 'Chemical', 'start': 1204, 'end': 1216, 'mesh': 'D017963'}, {'text': 'hiccups', 'type': 'Disease', 'start': 1246, 'end': 1253, 'mesh': 'D006606'}, {'text': 'hiccups', 'type': 'Disease', 'start': 1309, 'end': 1316, 'mesh': 'D006606'}, {'text': 'macrolide', 'type': 'Chemical', 'start': 1392, 'end': 1401, 'mesh': 'D018942'}, {'text': 'hiccups', 'type': 'Disease', 'start': 1458, 'end': 1465, 'mesh': 'D006606'}]"
+586,15276120,Time trends in warfarin-associated hemorrhage.,"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.","[{'text': 'warfarin', 'type': 'Chemical', 'start': 15, 'end': 23, 'mesh': 'D014859'}, {'text': 'hemorrhage', 'type': 'Disease', 'start': 35, 'end': 45, 'mesh': 'D006470'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 71, 'end': 79, 'mesh': 'D014859'}, {'text': 'bleeding', 'type': 'Disease', 'start': 88, 'end': 96, 'mesh': 'D006470'}, {'text': 'intracranial bleeding', 'type': 'Disease', 'start': 377, 'end': 398, 'mesh': 'D020300'}]"
+587,11271907,Fatal haemorrhagic myocarditis secondary to cyclophosphamide therapy.,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.,"[{'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 44, 'end': 60, 'mesh': 'D003520'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 135, 'end': 151, 'mesh': 'D003520'}]"
+588,10524660,Glyceryl trinitrate induces attacks of migraine without aura in sufferers of migraine with aura.,"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.","[{'text': 'Glyceryl trinitrate', 'type': 'Chemical', 'start': 0, 'end': 19, 'mesh': 'D005996'}, {'text': 'migraine without aura', 'type': 'Disease', 'start': 39, 'end': 60, 'mesh': 'D020326'}, {'text': 'migraine with aura', 'type': 'Disease', 'start': 77, 'end': 95, 'mesh': 'D020325'}, {'text': 'Migraine with aura', 'type': 'Disease', 'start': 97, 'end': 115, 'mesh': 'D020325'}, {'text': 'migraine without aura', 'type': 'Disease', 'start': 120, 'end': 141, 'mesh': 'D020326'}, {'text': 'pain', 'type': 'Disease', 'start': 156, 'end': 160, 'mesh': 'D010146'}, {'text': 'migraine with aura', 'type': 'Disease', 'start': 189, 'end': 207, 'mesh': 'D020325'}, {'text': 'migraine without aura', 'type': 'Disease', 'start': 212, 'end': 233, 'mesh': 'D020326'}, {'text': 'nitric oxide', 'type': 'Chemical', 'start': 352, 'end': 364, 'mesh': 'D009569'}, {'text': 'NO', 'type': 'Chemical', 'start': 366, 'end': 368, 'mesh': 'D009569'}, {'text': 'pain', 'type': 'Disease', 'start': 385, 'end': 389, 'mesh': 'D010146'}, {'text': 'migraine without aura', 'type': 'Disease', 'start': 404, 'end': 425, 'mesh': 'D020326'}, {'text': 'migraine with aura', 'type': 'Disease', 'start': 476, 'end': 494, 'mesh': 'D020325'}, {'text': 'headache', 'type': 'Disease', 'start': 533, 'end': 541, 'mesh': 'D006261'}, {'text': 'glyceryl trinitrate', 'type': 'Chemical', 'start': 578, 'end': 597, 'mesh': 'D005996'}, {'text': 'GTN', 'type': 'Chemical', 'start': 599, 'end': 602, 'mesh': 'D005996'}, {'text': 'migraine with aura', 'type': 'Disease', 'start': 654, 'end': 672, 'mesh': 'D020325'}, {'text': 'migraine without aura', 'type': 'Disease', 'start': 744, 'end': 765, 'mesh': 'D020326'}, {'text': 'Headache', 'type': 'Disease', 'start': 878, 'end': 886, 'mesh': 'D006261'}, {'text': 'migraineurs', 'type': 'Disease', 'start': 906, 'end': 917, 'mesh': 'D008881'}, {'text': 'GTN', 'type': 'Chemical', 'start': 968, 'end': 971, 'mesh': 'D005996'}, {'text': 'GTN', 'type': 'Chemical', 'start': 1062, 'end': 1065, 'mesh': 'D005996'}, {'text': 'headache', 'type': 'Disease', 'start': 1074, 'end': 1082, 'mesh': 'D006261'}, {'text': 'migraineurs', 'type': 'Disease', 'start': 1117, 'end': 1128, 'mesh': 'D008881'}, {'text': 'headache', 'type': 'Disease', 'start': 1134, 'end': 1142, 'mesh': 'D006261'}, {'text': 'headache', 'type': 'Disease', 'start': 1228, 'end': 1236, 'mesh': 'D006261'}, {'text': 'migraineurs', 'type': 'Disease', 'start': 1248, 'end': 1259, 'mesh': 'D008881'}, {'text': 'migraine without aura', 'type': 'Disease', 'start': 1298, 'end': 1319, 'mesh': 'D020326'}, {'text': 'Headache', 'type': 'Disease', 'start': 1341, 'end': 1349, 'mesh': 'D006261'}, {'text': 'NO', 'type': 'Chemical', 'start': 1394, 'end': 1396, 'mesh': 'D009569'}, {'text': 'pain', 'type': 'Disease', 'start': 1416, 'end': 1420, 'mesh': 'D010146'}, {'text': 'migraine with aura', 'type': 'Disease', 'start': 1435, 'end': 1453, 'mesh': 'D020325'}, {'text': 'depression', 'type': 'Disease', 'start': 1480, 'end': 1490, 'mesh': 'D003866'}, {'text': 'NO', 'type': 'Chemical', 'start': 1518, 'end': 1520, 'mesh': 'D009569'}, {'text': 'depression', 'type': 'Disease', 'start': 1616, 'end': 1626, 'mesh': 'D003866'}, {'text': 'headache', 'type': 'Disease', 'start': 1631, 'end': 1639, 'mesh': 'D006261'}, {'text': 'migraine with aura', 'type': 'Disease', 'start': 1643, 'end': 1661, 'mesh': 'D020325'}]"
+589,9799166,Stroke and cocaine or amphetamine use.,"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 population.","[{'text': 'Stroke', 'type': 'Disease', 'start': 0, 'end': 6, 'mesh': 'D020521'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 11, 'end': 18, 'mesh': 'D003042'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 22, 'end': 33, 'mesh': 'D000661'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 58, 'end': 65, 'mesh': 'D003042'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 70, 'end': 81, 'mesh': 'D000661'}, {'text': 'ischemic', 'type': 'Disease', 'start': 107, 'end': 115, 'mesh': 'D007511'}, {'text': 'stroke', 'type': 'Disease', 'start': 116, 'end': 122, 'mesh': 'D020521'}, {'text': 'stroke', 'type': 'Disease', 'start': 219, 'end': 225, 'mesh': 'D020521'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 237, 'end': 244, 'mesh': 'D003042'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 252, 'end': 263, 'mesh': 'D000661'}, {'text': 'strokes', 'type': 'Disease', 'start': 516, 'end': 523, 'mesh': 'D020521'}, {'text': 'stroke', 'type': 'Disease', 'start': 896, 'end': 902, 'mesh': 'D020521'}, {'text': 'stroke', 'type': 'Disease', 'start': 967, 'end': 973, 'mesh': 'D020521'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1005, 'end': 1012, 'mesh': 'D003042'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1020, 'end': 1031, 'mesh': 'D000661'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1173, 'end': 1180, 'mesh': 'D003042'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1188, 'end': 1199, 'mesh': 'D000661'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1257, 'end': 1264, 'mesh': 'D003042'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1272, 'end': 1283, 'mesh': 'D000661'}, {'text': 'stroke', 'type': 'Disease', 'start': 1312, 'end': 1318, 'mesh': 'D020521'}]"
+590,9672273,Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study.,"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.","[{'text': 'breast cancer', 'type': 'Disease', 'start': 14, 'end': 27, 'mesh': 'D001943'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 33, 'end': 42, 'mesh': 'D013629'}, {'text': 'Tamoxifen', 'type': 'Chemical', 'start': 136, 'end': 145, 'mesh': 'D013629'}, {'text': 'Tamoxifen', 'type': 'Chemical', 'start': 176, 'end': 185, 'mesh': 'D013629'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 226, 'end': 239, 'mesh': 'D001943'}, {'text': 'endometrial cancer', 'type': 'Disease', 'start': 301, 'end': 319, 'mesh': 'D016889'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 374, 'end': 383, 'mesh': 'D013629'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 499, 'end': 508, 'mesh': 'D013629'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 553, 'end': 566, 'mesh': 'D001943'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 632, 'end': 641, 'mesh': 'D013629'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 1065, 'end': 1078, 'mesh': 'D001943'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 1274, 'end': 1287, 'mesh': 'D001943'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 1336, 'end': 1349, 'mesh': 'D001943'}, {'text': 'breast-cancer', 'type': 'Disease', 'start': 1377, 'end': 1390, 'mesh': 'D001943'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 1436, 'end': 1445, 'mesh': 'D013629'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 1507, 'end': 1520, 'mesh': 'D001943'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 1543, 'end': 1552, 'mesh': 'D013629'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 1695, 'end': 1708, 'mesh': 'D001943'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 1761, 'end': 1770, 'mesh': 'D013629'}, {'text': 'vascular events', 'type': 'Disease', 'start': 1849, 'end': 1864, 'mesh': 'D014652'}, {'text': 'hypertriglyceridaemia', 'type': 'Disease', 'start': 1869, 'end': 1890, 'mesh': 'D015228'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 1906, 'end': 1915, 'mesh': 'D013629'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 2032, 'end': 2045, 'mesh': 'D001943'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 2084, 'end': 2093, 'mesh': 'D013629'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 2193, 'end': 2202, 'mesh': 'D013629'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 2230, 'end': 2243, 'mesh': 'D001943'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 2362, 'end': 2371, 'mesh': 'D013629'}]"
+591,8854309,A measure of pupillary oscillation as a marker of cocaine-induced paranoia.,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).,"[{'text': 'pupillary oscillation', 'type': 'Disease', 'start': 13, 'end': 34, 'mesh': 'D011681'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 50, 'end': 57, 'mesh': 'D003042'}, {'text': 'paranoia', 'type': 'Disease', 'start': 66, 'end': 74, 'mesh': 'D010259'}, {'text': 'Cocaine', 'type': 'Chemical', 'start': 76, 'end': 83, 'mesh': 'D003042'}, {'text': 'paranoia', 'type': 'Disease', 'start': 92, 'end': 100, 'mesh': 'D010259'}, {'text': 'CIP', 'type': 'Disease', 'start': 102, 'end': 105, 'mesh': 'D010259'}, {'text': 'paranoia', 'type': 'Disease', 'start': 161, 'end': 169, 'mesh': 'D010259'}, {'text': 'pupillary oscillation', 'type': 'Disease', 'start': 237, 'end': 258, 'mesh': 'D011681'}, {'text': 'crack cocaine', 'type': 'Chemical', 'start': 319, 'end': 332, 'mesh': 'D016578'}, {'text': 'CIP', 'type': 'Disease', 'start': 356, 'end': 359, 'mesh': 'D010259'}, {'text': 'crack', 'type': 'Chemical', 'start': 391, 'end': 396, 'mesh': 'D016578'}, {'text': 'CIP', 'type': 'Disease', 'start': 421, 'end': 424, 'mesh': 'D010259'}]"
+592,8473723,Seizures induced by combined levomepromazine-fluvoxamine treatment.,We report a case of combined levomepromazine-fluvoxamine treatment-induced seizures. It seems that combined treatment of fluvoxamine with phenothiazines may possess proconvulsive activity.,"[{'text': 'Seizures', 'type': 'Disease', 'start': 0, 'end': 8, 'mesh': 'D012640'}, {'text': 'levomepromazine', 'type': 'Chemical', 'start': 29, 'end': 44, 'mesh': 'D008728'}, {'text': 'fluvoxamine', 'type': 'Chemical', 'start': 45, 'end': 56, 'mesh': 'D016666'}, {'text': 'levomepromazine', 'type': 'Chemical', 'start': 97, 'end': 112, 'mesh': 'D008728'}, {'text': 'fluvoxamine', 'type': 'Chemical', 'start': 113, 'end': 124, 'mesh': 'D016666'}, {'text': 'seizures', 'type': 'Disease', 'start': 143, 'end': 151, 'mesh': 'D012640'}, {'text': 'fluvoxamine', 'type': 'Chemical', 'start': 189, 'end': 200, 'mesh': 'D016666'}, {'text': 'phenothiazines', 'type': 'Chemical', 'start': 206, 'end': 220, 'mesh': 'D010640'}]"
+593,6674249,Why may epsilon-aminocaproic acid (EACA) induce myopathy in man? Report of a case and literature review.,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.,"[{'text': 'epsilon-aminocaproic acid', 'type': 'Chemical', 'start': 8, 'end': 33, 'mesh': 'D015119'}, {'text': 'EACA', 'type': 'Chemical', 'start': 35, 'end': 39, 'mesh': 'D015119'}, {'text': 'myopathy', 'type': 'Disease', 'start': 48, 'end': 56, 'mesh': 'D009135'}, {'text': 'epsilon-aminocaproic acid', 'type': 'Chemical', 'start': 151, 'end': 176, 'mesh': 'D015119'}, {'text': 'EACA', 'type': 'Chemical', 'start': 178, 'end': 182, 'mesh': 'D015119'}, {'text': 'subarachnoid haemorrhage', 'type': 'Disease', 'start': 224, 'end': 248, 'mesh': 'D013345'}, {'text': 'SAH', 'type': 'Disease', 'start': 250, 'end': 253, 'mesh': 'D013345'}]"
+594,6150641,Comparison of the effectiveness of ranitidine and cimetidine in inhibiting acid secretion in patients with gastric hypersecretory states.,"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.","[{'text': 'ranitidine', 'type': 'Chemical', 'start': 35, 'end': 45, 'mesh': 'D011899'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 50, 'end': 60, 'mesh': 'D002927'}, {'text': 'histamine', 'type': 'Chemical', 'start': 145, 'end': 154, 'mesh': 'D006632'}, {'text': 'ranitidine', 'type': 'Chemical', 'start': 176, 'end': 186, 'mesh': 'D011899'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 191, 'end': 201, 'mesh': 'D002927'}, {'text': 'Zollinger-Ellison syndrome', 'type': 'Disease', 'start': 385, 'end': 411, 'mesh': 'D015043'}, {'text': 'systemic mastocytosis', 'type': 'Disease', 'start': 429, 'end': 450, 'mesh': 'D034721'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 536, 'end': 546, 'mesh': 'D002927'}, {'text': 'ranitidine', 'type': 'Chemical', 'start': 551, 'end': 561, 'mesh': 'D011899'}, {'text': 'ranitidine', 'type': 'Chemical', 'start': 770, 'end': 780, 'mesh': 'D011899'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 812, 'end': 822, 'mesh': 'D002927'}, {'text': 'ranitidine', 'type': 'Chemical', 'start': 917, 'end': 927, 'mesh': 'D011899'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 950, 'end': 960, 'mesh': 'D002927'}, {'text': 'impotence', 'type': 'Disease', 'start': 1018, 'end': 1027, 'mesh': 'D007172'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 1041, 'end': 1051, 'mesh': 'D002927'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 1100, 'end': 1110, 'mesh': 'D002927'}, {'text': 'ranitidine', 'type': 'Chemical', 'start': 1127, 'end': 1137, 'mesh': 'D011899'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 1168, 'end': 1178, 'mesh': 'D002927'}, {'text': 'ranitidine', 'type': 'Chemical', 'start': 1220, 'end': 1230, 'mesh': 'D011899'}, {'text': 'ranitidine', 'type': 'Chemical', 'start': 1377, 'end': 1387, 'mesh': 'D011899'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1444, 'end': 1454, 'mesh': 'D003404'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 1476, 'end': 1486, 'mesh': 'D002927'}, {'text': 'ranitidine', 'type': 'Chemical', 'start': 1648, 'end': 1658, 'mesh': 'D011899'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 1768, 'end': 1778, 'mesh': 'D002927'}]"
+595,3670965,A catch in the Reye.,"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.","[{'text': 'Reye', 'type': 'Disease', 'start': 15, 'end': 19, 'mesh': 'D012202'}, {'text': 'Reye syndrome', 'type': 'Disease', 'start': 41, 'end': 54, 'mesh': 'D012202'}, {'text': 'Reye syndrome', 'type': 'Disease', 'start': 265, 'end': 278, 'mesh': 'D012202'}, {'text': 'Aspirin', 'type': 'Chemical', 'start': 280, 'end': 287, 'mesh': 'D001241'}, {'text': 'salicylate', 'type': 'Chemical', 'start': 291, 'end': 301, 'mesh': 'D012459'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 363, 'end': 374, 'mesh': 'D000082'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 376, 'end': 389, 'mesh': 'D000082'}, {'text': 'Reye syndrome', 'type': 'Disease', 'start': 489, 'end': 502, 'mesh': 'D012202'}, {'text': 'Reye syndrome', 'type': 'Disease', 'start': 558, 'end': 571, 'mesh': 'D012202'}, {'text': 'Reye syndrome', 'type': 'Disease', 'start': 847, 'end': 860, 'mesh': 'D012202'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 989, 'end': 996, 'mesh': 'D001241'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 1090, 'end': 1101, 'mesh': 'D000082'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 1103, 'end': 1116, 'mesh': 'D000082'}, {'text': 'Reye syndrome', 'type': 'Disease', 'start': 1177, 'end': 1190, 'mesh': 'D012202'}, {'text': 'salicylates', 'type': 'Chemical', 'start': 1267, 'end': 1278, 'mesh': 'D012459'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1282, 'end': 1289, 'mesh': 'D001241'}]"
+596,3300918,"St. Anthony's fire, then and now: a case report and historical review.","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.","[{'text': ""St. Anthony's fire"", 'type': 'Disease', 'start': 0, 'end': 18, 'mesh': 'D004881'}, {'text': 'vasospasm', 'type': 'Disease', 'start': 93, 'end': 102, 'mesh': 'D014652'}, {'text': 'methysergide', 'type': 'Chemical', 'start': 193, 'end': 205, 'mesh': 'D008784'}, {'text': 'ergot', 'type': 'Chemical', 'start': 325, 'end': 330, 'mesh': 'D004876'}, {'text': 'gangrene', 'type': 'Disease', 'start': 381, 'end': 389, 'mesh': 'D005734'}, {'text': 'migraine headache', 'type': 'Disease', 'start': 477, 'end': 494, 'mesh': 'D008881'}, {'text': 'calcium', 'type': 'Chemical', 'start': 518, 'end': 525, 'mesh': 'D002118'}, {'text': 'ergot', 'type': 'Chemical', 'start': 576, 'end': 581, 'mesh': 'D004876'}, {'text': 'migraine', 'type': 'Disease', 'start': 628, 'end': 636, 'mesh': 'D008881'}, {'text': ""St. Anthony's fire"", 'type': 'Disease', 'start': 668, 'end': 686, 'mesh': 'D004881'}]"
+597,2826064,Beta-2-adrenoceptor-mediated hypokalemia and its abolishment by oxprenolol.,"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.","[{'text': 'hypokalemia', 'type': 'Disease', 'start': 29, 'end': 40, 'mesh': 'D007008'}, {'text': 'oxprenolol', 'type': 'Chemical', 'start': 64, 'end': 74, 'mesh': 'D010096'}, {'text': 'terbutaline', 'type': 'Chemical', 'start': 133, 'end': 144, 'mesh': 'D013726'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 153, 'end': 164, 'mesh': 'D007008'}, {'text': 'oxprenolol', 'type': 'Chemical', 'start': 278, 'end': 288, 'mesh': 'D010096'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 310, 'end': 321, 'mesh': 'D007008'}, {'text': 'terbutaline', 'type': 'Chemical', 'start': 451, 'end': 462, 'mesh': 'D013726'}, {'text': 'oxprenolol', 'type': 'Chemical', 'start': 550, 'end': 560, 'mesh': 'D010096'}, {'text': 'terbutaline', 'type': 'Chemical', 'start': 596, 'end': 607, 'mesh': 'D013726'}, {'text': 'potassium', 'type': 'Chemical', 'start': 678, 'end': 687, 'mesh': 'D011188'}, {'text': 'terbutaline', 'type': 'Chemical', 'start': 794, 'end': 805, 'mesh': 'D013726'}, {'text': 'potassium', 'type': 'Chemical', 'start': 825, 'end': 834, 'mesh': 'D011188'}, {'text': 'Oxprenolol', 'type': 'Chemical', 'start': 844, 'end': 854, 'mesh': 'D010096'}, {'text': 'terbutaline', 'type': 'Chemical', 'start': 890, 'end': 901, 'mesh': 'D013726'}, {'text': 'terbutaline', 'type': 'Chemical', 'start': 1009, 'end': 1020, 'mesh': 'D013726'}, {'text': 'oxprenolol', 'type': 'Chemical', 'start': 1042, 'end': 1052, 'mesh': 'D010096'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 1071, 'end': 1082, 'mesh': 'D007008'}]"
+598,2422478,Midline B3 serotonin nerves in rat medulla are involved in hypotensive effect of methyldopa.,"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.","[{'text': 'serotonin', 'type': 'Chemical', 'start': 11, 'end': 20, 'mesh': 'D012701'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 59, 'end': 70, 'mesh': 'D007022'}, {'text': 'methyldopa', 'type': 'Chemical', 'start': 81, 'end': 91, 'mesh': 'D008750'}, {'text': 'methyldopa', 'type': 'Chemical', 'start': 167, 'end': 177, 'mesh': 'D008750'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 217, 'end': 226, 'mesh': 'D012701'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 260, 'end': 271, 'mesh': 'D007022'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 432, 'end': 441, 'mesh': 'D012701'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 517, 'end': 529, 'mesh': 'D006973'}, {'text': 'stroke', 'type': 'Disease', 'start': 531, 'end': 537, 'mesh': 'D020521'}, {'text': 'methyldopa', 'type': 'Chemical', 'start': 568, 'end': 578, 'mesh': 'D008750'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 611, 'end': 620, 'mesh': 'D012701'}, {'text': 'hypotension', 'type': 'Disease', 'start': 671, 'end': 682, 'mesh': 'D007022'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 769, 'end': 778, 'mesh': 'D012701'}, {'text': '5,7-dihydroxytryptamine', 'type': 'Chemical', 'start': 790, 'end': 813, 'mesh': 'D015116'}, {'text': '5,7-DHT', 'type': 'Chemical', 'start': 815, 'end': 822, 'mesh': 'D015116'}, {'text': '5,7-DHT', 'type': 'Chemical', 'start': 894, 'end': 901, 'mesh': 'D015116'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 956, 'end': 965, 'mesh': 'D012701'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1017, 'end': 1028, 'mesh': 'D007022'}, {'text': '5,7-DHT', 'type': 'Chemical', 'start': 1039, 'end': 1046, 'mesh': 'D015116'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 1057, 'end': 1066, 'mesh': 'D012701'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 1164, 'end': 1173, 'mesh': 'D012701'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 1252, 'end': 1261, 'mesh': 'D012701'}, {'text': 'methyldopa', 'type': 'Chemical', 'start': 1262, 'end': 1272, 'mesh': 'D008750'}, {'text': 'methyldopa', 'type': 'Chemical', 'start': 1366, 'end': 1376, 'mesh': 'D008750'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1385, 'end': 1396, 'mesh': 'D007022'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 1437, 'end': 1446, 'mesh': 'D012701'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 1489, 'end': 1500, 'mesh': 'D007022'}, {'text': 'methyldopa', 'type': 'Chemical', 'start': 1511, 'end': 1521, 'mesh': 'D008750'}]"
+599,1535072,Yohimbine treatment of sexual side effects induced by serotonin reuptake blockers.,"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.","[{'text': 'Yohimbine', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D015016'}, {'text': 'sexual side effects', 'type': 'Disease', 'start': 23, 'end': 42, 'mesh': 'D020018'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 54, 'end': 63, 'mesh': 'D012701'}, {'text': 'yohimbine', 'type': 'Chemical', 'start': 141, 'end': 150, 'mesh': 'D015016'}, {'text': 'male impotence', 'type': 'Disease', 'start': 218, 'end': 232, 'mesh': 'D007172'}, {'text': 'yohimbine', 'type': 'Chemical', 'start': 269, 'end': 278, 'mesh': 'D015016'}, {'text': 'sexual side effects', 'type': 'Disease', 'start': 304, 'end': 323, 'mesh': 'D020018'}, {'text': 'clomipramine', 'type': 'Chemical', 'start': 327, 'end': 339, 'mesh': 'D002997'}, {'text': 'yohimbine', 'type': 'Chemical', 'start': 362, 'end': 371, 'mesh': 'D015016'}, {'text': 'sexual side effects', 'type': 'Disease', 'start': 395, 'end': 414, 'mesh': 'D020018'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 425, 'end': 434, 'mesh': 'D012701'}, {'text': 'obsessive compulsive disorder', 'type': 'Disease', 'start': 487, 'end': 516, 'mesh': 'D009771'}, {'text': 'trichotillomania', 'type': 'Disease', 'start': 518, 'end': 534, 'mesh': 'D014256'}, {'text': 'anxiety', 'type': 'Disease', 'start': 536, 'end': 543, 'mesh': 'D001008'}, {'text': 'affective disorders', 'type': 'Disease', 'start': 548, 'end': 567, 'mesh': 'D019964'}, {'text': 'sexual side effects', 'type': 'Disease', 'start': 581, 'end': 600, 'mesh': 'D020018'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 622, 'end': 631, 'mesh': 'D012701'}, {'text': 'yohimbine', 'type': 'Chemical', 'start': 661, 'end': 670, 'mesh': 'D015016'}, {'text': 'yohimbine', 'type': 'Chemical', 'start': 733, 'end': 742, 'mesh': 'D015016'}, {'text': 'yohimbine', 'type': 'Chemical', 'start': 886, 'end': 895, 'mesh': 'D015016'}, {'text': 'yohimbine', 'type': 'Chemical', 'start': 935, 'end': 944, 'mesh': 'D015016'}, {'text': 'yohimbine', 'type': 'Chemical', 'start': 999, 'end': 1008, 'mesh': 'D015016'}, {'text': 'anxiety', 'type': 'Disease', 'start': 1048, 'end': 1055, 'mesh': 'D001008'}, {'text': 'yohimbine', 'type': 'Chemical', 'start': 1150, 'end': 1159, 'mesh': 'D015016'}, {'text': 'sexual side effects', 'type': 'Disease', 'start': 1198, 'end': 1217, 'mesh': 'D020018'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 1228, 'end': 1237, 'mesh': 'D012701'}, {'text': 'yohimbine', 'type': 'Chemical', 'start': 1349, 'end': 1358, 'mesh': 'D015016'}]"
+600,1504402,Hypersensitivity immune reaction as a mechanism for dilevalol-associated hepatitis.,"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.","[{'text': 'Hypersensitivity', 'type': 'Disease', 'start': 0, 'end': 16, 'mesh': 'D004342'}, {'text': 'dilevalol', 'type': 'Chemical', 'start': 52, 'end': 61, 'mesh': 'D007741'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 73, 'end': 82, 'mesh': 'D056486'}, {'text': 'dilevalol', 'type': 'Chemical', 'start': 130, 'end': 139, 'mesh': 'D007741'}, {'text': 'dilevalol', 'type': 'Chemical', 'start': 181, 'end': 190, 'mesh': 'D007741'}, {'text': 'dilevalol', 'type': 'Chemical', 'start': 228, 'end': 237, 'mesh': 'D007741'}, {'text': 'liver injury', 'type': 'Disease', 'start': 246, 'end': 258, 'mesh': 'D056486'}, {'text': 'dilevalol', 'type': 'Chemical', 'start': 318, 'end': 327, 'mesh': 'D007741'}, {'text': 'liver injury', 'type': 'Disease', 'start': 336, 'end': 348, 'mesh': 'D056486'}, {'text': 'dilevalol', 'type': 'Chemical', 'start': 468, 'end': 477, 'mesh': 'D007741'}, {'text': 'dilevalol', 'type': 'Chemical', 'start': 541, 'end': 550, 'mesh': 'D007741'}, {'text': 'dilevalol', 'type': 'Chemical', 'start': 752, 'end': 761, 'mesh': 'D007741'}, {'text': 'dilevalol', 'type': 'Chemical', 'start': 835, 'end': 844, 'mesh': 'D007741'}, {'text': 'dilevalol', 'type': 'Chemical', 'start': 1204, 'end': 1213, 'mesh': 'D007741'}, {'text': 'dilevalol', 'type': 'Chemical', 'start': 1282, 'end': 1291, 'mesh': 'D007741'}, {'text': 'liver injury', 'type': 'Disease', 'start': 1300, 'end': 1312, 'mesh': 'D056486'}]"
+601,19917396,Reversible myocardial hypertrophy induced by tacrolimus in a pediatric heart transplant recipient: case report.,"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.","[{'text': 'myocardial hypertrophy', 'type': 'Disease', 'start': 11, 'end': 33, 'mesh': 'D006332'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 45, 'end': 55, 'mesh': 'D016559'}, {'text': 'Tacrolimus', 'type': 'Chemical', 'start': 112, 'end': 122, 'mesh': 'D016559'}, {'text': 'cardiac toxicity', 'type': 'Disease', 'start': 236, 'end': 252, 'mesh': 'D066126'}, {'text': 'myocardial hypertrophy', 'type': 'Disease', 'start': 283, 'end': 305, 'mesh': 'D006332'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 317, 'end': 327, 'mesh': 'D016559'}, {'text': 'hypertrophy', 'type': 'Disease', 'start': 361, 'end': 372, 'mesh': 'D006984'}, {'text': 'edema', 'type': 'Disease', 'start': 626, 'end': 631, 'mesh': 'D004487'}, {'text': 'myocardial hypertrophy', 'type': 'Disease', 'start': 641, 'end': 663, 'mesh': 'D006332'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 728, 'end': 738, 'mesh': 'D016559'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 795, 'end': 805, 'mesh': 'D016559'}, {'text': 'Myocardial hypertrophy', 'type': 'Disease', 'start': 826, 'end': 848, 'mesh': 'D006332'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 911, 'end': 921, 'mesh': 'D016559'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 1020, 'end': 1030, 'mesh': 'D016559'}, {'text': 'myocardial hypertrophy', 'type': 'Disease', 'start': 1050, 'end': 1072, 'mesh': 'D006332'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 1096, 'end': 1106, 'mesh': 'D016559'}]"
+602,19234905,Comparison of unilateral pallidotomy and subthalamotomy findings in advanced idiopathic Parkinson's disease.,"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.","[{'text': ""idiopathic Parkinson's disease"", 'type': 'Disease', 'start': 77, 'end': 107, 'mesh': 'D010300'}, {'text': ""idiopathic Parkinson's disease"", 'type': 'Disease', 'start': 254, 'end': 284, 'mesh': 'D010300'}, {'text': 'PD', 'type': 'Disease', 'start': 286, 'end': 288, 'mesh': 'D010300'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 581, 'end': 589, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 598, 'end': 609, 'mesh': 'D004409'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 671, 'end': 679, 'mesh': 'D007980'}, {'text': ""Parkinson's Disease"", 'type': 'Disease', 'start': 875, 'end': 894, 'mesh': 'D010300'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 1145, 'end': 1157, 'mesh': 'D010300'}, {'text': 'Levodopa', 'type': 'Chemical', 'start': 1209, 'end': 1217, 'mesh': 'D007980'}, {'text': 'homonymous hemianopsia', 'type': 'Disease', 'start': 1487, 'end': 1509, 'mesh': 'D006423'}, {'text': 'Valproate', 'type': 'Chemical', 'start': 1653, 'end': 1662, 'mesh': 'D014635'}, {'text': 'PD', 'type': 'Disease', 'start': 1813, 'end': 1815, 'mesh': 'D010300'}]"
+603,18541230,Protective effects of antithrombin on puromycin aminonucleoside nephrosis in rats.,"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.","[{'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 38, 'end': 63, 'mesh': 'D011692'}, {'text': 'nephrosis', 'type': 'Disease', 'start': 64, 'end': 73, 'mesh': 'D009401'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 184, 'end': 209, 'mesh': 'D011692'}, {'text': 'nephrosis', 'type': 'Disease', 'start': 218, 'end': 227, 'mesh': 'D009401'}, {'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 269, 'end': 287, 'mesh': 'D009404'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 408, 'end': 433, 'mesh': 'D011692'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 494, 'end': 519, 'mesh': 'D011692'}, {'text': 'hematological abnormalities', 'type': 'Disease', 'start': 528, 'end': 555, 'mesh': 'D006402'}, {'text': 'Puromycin aminonucleoside', 'type': 'Chemical', 'start': 557, 'end': 582, 'mesh': 'D011692'}, {'text': 'renal dysfunction', 'type': 'Disease', 'start': 591, 'end': 608, 'mesh': 'D007674'}, {'text': 'hyperlipidemia', 'type': 'Disease', 'start': 613, 'end': 627, 'mesh': 'D006949'}, {'text': 'renal damage', 'type': 'Disease', 'start': 696, 'end': 708, 'mesh': 'D007674'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 930, 'end': 955, 'mesh': 'D011692'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 1022, 'end': 1047, 'mesh': 'D011692'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 1197, 'end': 1222, 'mesh': 'D011692'}, {'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 1231, 'end': 1249, 'mesh': 'D009404'}, {'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 1324, 'end': 1342, 'mesh': 'D009404'}]"
+604,18177388,Reverse or inverted left ventricular apical ballooning syndrome (reverse Takotsubo cardiomyopathy) in a young woman in the setting of amphetamine use.,"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.","[{'text': 'left ventricular apical ballooning syndrome', 'type': 'Disease', 'start': 20, 'end': 63, 'mesh': 'D054549'}, {'text': 'Takotsubo cardiomyopathy', 'type': 'Disease', 'start': 73, 'end': 97, 'mesh': 'D054549'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 134, 'end': 145, 'mesh': 'D000661'}, {'text': 'left ventricular apical ballooning syndrome', 'type': 'Disease', 'start': 161, 'end': 204, 'mesh': 'D054549'}, {'text': 'Takotsubo cardiomyopathy', 'type': 'Disease', 'start': 238, 'end': 262, 'mesh': 'D054549'}, {'text': 'akinesia', 'type': 'Disease', 'start': 497, 'end': 505, 'mesh': 'D004409'}, {'text': 'apical ballooning', 'type': 'Disease', 'start': 545, 'end': 562, 'mesh': 'D054549'}, {'text': 'apical ballooning syndrome', 'type': 'Disease', 'start': 674, 'end': 700, 'mesh': 'D054549'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 717, 'end': 728, 'mesh': 'D000661'}]"
+605,17490864,Attenuated disruption of prepulse inhibition by dopaminergic stimulation after maternal deprivation and adolescent corticosterone treatment in rats.,"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.","[{'text': 'corticosterone', 'type': 'Chemical', 'start': 115, 'end': 129, 'mesh': 'D003345'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 168, 'end': 181, 'mesh': 'D012559'}, {'text': 'corticosterone', 'type': 'Chemical', 'start': 492, 'end': 506, 'mesh': 'D003345'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 561, 'end': 572, 'mesh': 'D001058'}, {'text': 'corticosterone', 'type': 'Chemical', 'start': 694, 'end': 708, 'mesh': 'D003345'}, {'text': 'Amphetamine', 'type': 'Chemical', 'start': 811, 'end': 822, 'mesh': 'D000661'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 945, 'end': 954, 'mesh': 'D012701'}, {'text': '8-OH-DPAT', 'type': 'Chemical', 'start': 976, 'end': 985, 'mesh': 'D017371'}, {'text': 'Amphetamine', 'type': 'Chemical', 'start': 1042, 'end': 1053, 'mesh': 'D000661'}, {'text': 'locomotor hyperactivity', 'type': 'Disease', 'start': 1062, 'end': 1085, 'mesh': 'D006948'}, {'text': 'corticosterone', 'type': 'Chemical', 'start': 1255, 'end': 1269, 'mesh': 'D003345'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 1339, 'end': 1350, 'mesh': 'D001058'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1355, 'end': 1366, 'mesh': 'D000661'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1406, 'end': 1414, 'mesh': 'D004298'}]"
+606,17490790,Peripheral iron dextran induced degeneration of dopaminergic neurons in rat substantia nigra.,"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.","[{'text': 'iron dextran', 'type': 'Chemical', 'start': 11, 'end': 23, 'mesh': 'D007505'}, {'text': 'degeneration of dopaminergic neurons', 'type': 'Disease', 'start': 32, 'end': 68, 'mesh': 'D009410'}, {'text': 'Iron', 'type': 'Chemical', 'start': 94, 'end': 98, 'mesh': 'D007501'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 164, 'end': 183, 'mesh': 'D010300'}, {'text': 'iron', 'type': 'Chemical', 'start': 236, 'end': 240, 'mesh': 'D007501'}, {'text': 'tyrosine', 'type': 'Chemical', 'start': 363, 'end': 371, 'mesh': 'D014443'}, {'text': 'iron', 'type': 'Chemical', 'start': 418, 'end': 422, 'mesh': 'D007501'}, {'text': 'degeneration of dopaminergic neurons', 'type': 'Disease', 'start': 515, 'end': 551, 'mesh': 'D009410'}, {'text': 'iron', 'type': 'Chemical', 'start': 566, 'end': 570, 'mesh': 'D007501'}, {'text': 'iron dextran', 'type': 'Chemical', 'start': 592, 'end': 604, 'mesh': 'D007505'}, {'text': 'iron dextran', 'type': 'Chemical', 'start': 661, 'end': 673, 'mesh': 'D007505'}, {'text': 'iron', 'type': 'Chemical', 'start': 697, 'end': 701, 'mesh': 'D007501'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 802, 'end': 810, 'mesh': 'D004298'}, {'text': 'iron dextran', 'type': 'Chemical', 'start': 1006, 'end': 1018, 'mesh': 'D007505'}, {'text': 'iron', 'type': 'Chemical', 'start': 1036, 'end': 1040, 'mesh': 'D007501'}, {'text': 'iron', 'type': 'Chemical', 'start': 1074, 'end': 1078, 'mesh': 'D007501'}, {'text': 'degeneration of dopaminergic neurons', 'type': 'Disease', 'start': 1090, 'end': 1126, 'mesh': 'D009410'}, {'text': 'iron', 'type': 'Chemical', 'start': 1140, 'end': 1144, 'mesh': 'D007501'}, {'text': 'iron', 'type': 'Chemical', 'start': 1217, 'end': 1221, 'mesh': 'D007501'}]"
+607,16047871,Warfarin-induced leukocytoclastic vasculitis.,"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.","[{'text': 'Warfarin', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D014859'}, {'text': 'leukocytoclastic vasculitis', 'type': 'Disease', 'start': 17, 'end': 44, 'mesh': 'C535509'}, {'text': 'coumarin', 'type': 'Chemical', 'start': 82, 'end': 90, 'mesh': 'C030123'}, {'text': 'Leukocytoclastic vasculitis', 'type': 'Disease', 'start': 142, 'end': 169, 'mesh': 'C535509'}, {'text': 'LV', 'type': 'Disease', 'start': 171, 'end': 173, 'mesh': 'C535509'}, {'text': 'cutaneous small vessel vasculitis', 'type': 'Disease', 'start': 190, 'end': 223, 'mesh': 'C565222'}, {'text': 'LV', 'type': 'Disease', 'start': 310, 'end': 312, 'mesh': 'C535509'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 329, 'end': 337, 'mesh': 'D014859'}, {'text': 'skin eruptions', 'type': 'Disease', 'start': 369, 'end': 383, 'mesh': 'D012871'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 415, 'end': 423, 'mesh': 'D014859'}, {'text': 'skin lesion', 'type': 'Disease', 'start': 458, 'end': 469, 'mesh': 'D012871'}, {'text': 'LV Cutaneous lesions', 'type': 'Disease', 'start': 520, 'end': 540, 'mesh': 'D018366'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 572, 'end': 580, 'mesh': 'D014859'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 640, 'end': 648, 'mesh': 'D014859'}, {'text': 'LV', 'type': 'Disease', 'start': 683, 'end': 685, 'mesh': 'C535509'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 739, 'end': 747, 'mesh': 'D014859'}]"
+608,15673851,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.,"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.","[{'text': 'N-methyl-D-aspartate', 'type': 'Chemical', 'start': 25, 'end': 45, 'mesh': 'D016202'}, {'text': 'morphine', 'type': 'Chemical', 'start': 132, 'end': 140, 'mesh': 'D009020'}, {'text': 'spinal cord ischemia', 'type': 'Disease', 'start': 174, 'end': 194, 'mesh': 'D020760'}, {'text': 'N-methyl-d-aspartate', 'type': 'Chemical', 'start': 296, 'end': 316, 'mesh': 'D016202'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 318, 'end': 322, 'mesh': 'D016202'}, {'text': 'morphine', 'type': 'Chemical', 'start': 350, 'end': 358, 'mesh': 'D009020'}, {'text': 'aortic occlusion', 'type': 'Disease', 'start': 396, 'end': 412, 'mesh': 'D001157'}, {'text': 'Spinal cord ischemia', 'type': 'Disease', 'start': 422, 'end': 442, 'mesh': 'D020760'}, {'text': 'aortic occlusion', 'type': 'Disease', 'start': 458, 'end': 474, 'mesh': 'D001157'}, {'text': 'morphine', 'type': 'Chemical', 'start': 583, 'end': 591, 'mesh': 'D009020'}, {'text': 'morphine', 'type': 'Chemical', 'start': 675, 'end': 683, 'mesh': 'D009020'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 962, 'end': 968, 'mesh': 'D016291'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1034, 'end': 1042, 'mesh': 'D009020'}, {'text': 'spastic paraparesis', 'type': 'Disease', 'start': 1051, 'end': 1070, 'mesh': 'D020336'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1081, 'end': 1089, 'mesh': 'D009020'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 1121, 'end': 1130, 'mesh': 'D018698'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 1258, 'end': 1264, 'mesh': 'D016291'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1338, 'end': 1346, 'mesh': 'D009020'}, {'text': 'spastic paraparesis', 'type': 'Disease', 'start': 1355, 'end': 1374, 'mesh': 'D020336'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1435, 'end': 1443, 'mesh': 'D009020'}, {'text': 'spastic paraparesis', 'type': 'Disease', 'start': 1452, 'end': 1471, 'mesh': 'D020336'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 1507, 'end': 1516, 'mesh': 'D018698'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 1539, 'end': 1543, 'mesh': 'D016202'}, {'text': 'neurotoxic', 'type': 'Disease', 'start': 1596, 'end': 1606, 'mesh': 'D020258'}, {'text': 'spinal cord ischemia', 'type': 'Disease', 'start': 1625, 'end': 1645, 'mesh': 'D020760'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 1650, 'end': 1654, 'mesh': 'D016202'}]"
+609,12481039,"Reduced sodium channel density, altered voltage dependence of inactivation, and increased susceptibility to seizures in mice lacking sodium channel beta 2-subunits.","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.","[{'text': 'sodium', 'type': 'Chemical', 'start': 8, 'end': 14, 'mesh': 'D012964'}, {'text': 'seizures', 'type': 'Disease', 'start': 108, 'end': 116, 'mesh': 'D012640'}, {'text': 'sodium', 'type': 'Chemical', 'start': 133, 'end': 139, 'mesh': 'D012964'}, {'text': 'Sodium', 'type': 'Chemical', 'start': 165, 'end': 171, 'mesh': 'D012964'}, {'text': 'sodium', 'type': 'Chemical', 'start': 363, 'end': 369, 'mesh': 'D012964'}, {'text': 'saxitoxin', 'type': 'Chemical', 'start': 456, 'end': 465, 'mesh': 'D012530'}, {'text': 'STX', 'type': 'Chemical', 'start': 467, 'end': 470, 'mesh': 'D012530'}, {'text': 'sodium', 'type': 'Chemical', 'start': 543, 'end': 549, 'mesh': 'D012964'}, {'text': 'sodium', 'type': 'Chemical', 'start': 706, 'end': 712, 'mesh': 'D012964'}, {'text': 'sodium', 'type': 'Chemical', 'start': 992, 'end': 998, 'mesh': 'D012964'}, {'text': 'Na', 'type': 'Chemical', 'start': 1129, 'end': 1131, 'mesh': 'D012964'}, {'text': 'seizures', 'type': 'Disease', 'start': 1241, 'end': 1249, 'mesh': 'D012640'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1301, 'end': 1312, 'mesh': 'D010862'}, {'text': 'seizures', 'type': 'Disease', 'start': 1321, 'end': 1329, 'mesh': 'D012640'}, {'text': 'sodium', 'type': 'Chemical', 'start': 1464, 'end': 1470, 'mesh': 'D012964'}]"
+610,11185967,Screening for stimulant use in adult emergency department seizure patients.,"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.","[{'text': 'seizure', 'type': 'Disease', 'start': 58, 'end': 65, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 185, 'end': 192, 'mesh': 'D003042'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 196, 'end': 207, 'mesh': 'D000661'}, {'text': 'seizure', 'type': 'Disease', 'start': 238, 'end': 245, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 319, 'end': 326, 'mesh': 'D012640'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 430, 'end': 441, 'mesh': 'D000661'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 450, 'end': 457, 'mesh': 'D003042'}, {'text': 'benzoylecgonine', 'type': 'Chemical', 'start': 469, 'end': 484, 'mesh': 'C005618'}, {'text': 'benzoylecgonine', 'type': 'Chemical', 'start': 552, 'end': 567, 'mesh': 'C005618'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 597, 'end': 608, 'mesh': 'D000661'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 710, 'end': 717, 'mesh': 'D000431'}, {'text': 'seizure', 'type': 'Disease', 'start': 726, 'end': 733, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 764, 'end': 771, 'mesh': 'D012640'}, {'text': 'benzoylecgonine', 'type': 'Chemical', 'start': 1069, 'end': 1084, 'mesh': 'C005618'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1138, 'end': 1149, 'mesh': 'D000661'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1361, 'end': 1368, 'mesh': 'D003042'}, {'text': 'amphetamines', 'type': 'Chemical', 'start': 1373, 'end': 1385, 'mesh': 'D000662'}, {'text': 'seizure', 'type': 'Disease', 'start': 1395, 'end': 1402, 'mesh': 'D012640'}, {'text': 'drug abuse', 'type': 'Disease', 'start': 1561, 'end': 1571, 'mesh': 'D019966'}]"
+611,11099450,Evidence of functional somatotopy in GPi from results of pallidotomy.,"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.","[{'text': 'parkinsonian', 'type': 'Disease', 'start': 227, 'end': 239, 'mesh': 'D010300'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 256, 'end': 264, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 273, 'end': 284, 'mesh': 'D004409'}, {'text': 'LID', 'type': 'Disease', 'start': 286, 'end': 289, 'mesh': 'D004409'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 360, 'end': 368, 'mesh': 'D007980'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 407, 'end': 415, 'mesh': 'D007980'}, {'text': 'LID', 'type': 'Disease', 'start': 652, 'end': 655, 'mesh': 'D004409'}, {'text': 'LID', 'type': 'Disease', 'start': 802, 'end': 805, 'mesh': 'D004409'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 917, 'end': 929, 'mesh': 'D010300'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 1051, 'end': 1062, 'mesh': 'D004409'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 1066, 'end': 1078, 'mesh': 'D010300'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1129, 'end': 1137, 'mesh': 'D007980'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 1172, 'end': 1184, 'mesh': 'D010300'}, {'text': 'LID', 'type': 'Disease', 'start': 1201, 'end': 1204, 'mesh': 'D004409'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 1266, 'end': 1277, 'mesh': 'D004409'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 1282, 'end': 1294, 'mesh': 'D010300'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 1416, 'end': 1428, 'mesh': 'D010300'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 1445, 'end': 1456, 'mesh': 'D004409'}, {'text': 'parkinsonism', 'type': 'Disease', 'start': 1520, 'end': 1532, 'mesh': 'D010300'}, {'text': 'LID', 'type': 'Disease', 'start': 1595, 'end': 1598, 'mesh': 'D004409'}, {'text': 'parkinsonism', 'type': 'Disease', 'start': 1726, 'end': 1738, 'mesh': 'D010300'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 1743, 'end': 1754, 'mesh': 'D004409'}]"
+612,11027904,Pain responses in methadone-maintained opioid abusers.,"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.","[{'text': 'Pain', 'type': 'Disease', 'start': 0, 'end': 4, 'mesh': 'D010146'}, {'text': 'methadone', 'type': 'Chemical', 'start': 18, 'end': 27, 'mesh': 'D008691'}, {'text': 'pain', 'type': 'Disease', 'start': 65, 'end': 69, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 182, 'end': 186, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 262, 'end': 266, 'mesh': 'D010146'}, {'text': 'opioid addicts', 'type': 'Disease', 'start': 315, 'end': 329, 'mesh': 'D009293'}, {'text': 'methadone', 'type': 'Chemical', 'start': 344, 'end': 353, 'mesh': 'D008691'}, {'text': 'pain', 'type': 'Disease', 'start': 543, 'end': 547, 'mesh': 'D010146'}, {'text': 'hydromorphone', 'type': 'Chemical', 'start': 643, 'end': 656, 'mesh': 'D004091'}, {'text': 'ketorolac', 'type': 'Chemical', 'start': 699, 'end': 708, 'mesh': 'D020910'}, {'text': 'pain', 'type': 'Disease', 'start': 808, 'end': 812, 'mesh': 'D010146'}, {'text': 'pain-intolerant', 'type': 'Disease', 'start': 987, 'end': 1002, 'mesh': 'D006930'}, {'text': 'pain', 'type': 'Disease', 'start': 1052, 'end': 1056, 'mesh': 'D010146'}]"
+613,10193809,Urine N-acetyl-beta-D-glucosaminidase--a marker of tubular damage?,"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.","[{'text': 'renal tubular dysfunction', 'type': 'Disease', 'start': 104, 'end': 129, 'mesh': 'D005198'}, {'text': 'Puromycin aminonucleoside', 'type': 'Chemical', 'start': 275, 'end': 300, 'mesh': 'D011692'}, {'text': 'PAN', 'type': 'Chemical', 'start': 302, 'end': 305, 'mesh': 'D011692'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 357, 'end': 368, 'mesh': 'D011507'}, {'text': 'PAN', 'type': 'Chemical', 'start': 705, 'end': 708, 'mesh': 'D011692'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1219, 'end': 1230, 'mesh': 'D011507'}]"
+614,9214597,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.,"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.","[{'text': 'estrogen', 'type': 'Chemical', 'start': 97, 'end': 105, 'mesh': 'D004967'}, {'text': 'pituitary tumors', 'type': 'Disease', 'start': 118, 'end': 134, 'mesh': 'D010911'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 147, 'end': 155, 'mesh': 'D004967'}, {'text': 'tumor', 'type': 'Disease', 'start': 166, 'end': 171, 'mesh': 'D009369'}, {'text': 'Estrogens', 'type': 'Chemical', 'start': 186, 'end': 195, 'mesh': 'D004967'}, {'text': 'cancers', 'type': 'Disease', 'start': 263, 'end': 270, 'mesh': 'D009369'}, {'text': 'tumor', 'type': 'Disease', 'start': 283, 'end': 288, 'mesh': 'D009369'}, {'text': 'tumor', 'type': 'Disease', 'start': 367, 'end': 372, 'mesh': 'D009369'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 404, 'end': 412, 'mesh': 'D004967'}, {'text': 'carcinogenesis', 'type': 'Disease', 'start': 413, 'end': 427, 'mesh': 'D063646'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 473, 'end': 481, 'mesh': 'D004967'}, {'text': 'tumor', 'type': 'Disease', 'start': 503, 'end': 508, 'mesh': 'D009369'}, {'text': '17beta-estradiol', 'type': 'Chemical', 'start': 948, 'end': 964, 'mesh': 'D004958'}, {'text': 'E2', 'type': 'Chemical', 'start': 966, 'end': 968, 'mesh': 'D004958'}, {'text': 'tumor', 'type': 'Disease', 'start': 1088, 'end': 1093, 'mesh': 'D009369'}, {'text': 'E2', 'type': 'Chemical', 'start': 1182, 'end': 1184, 'mesh': 'D004958'}, {'text': 'E2', 'type': 'Chemical', 'start': 1473, 'end': 1475, 'mesh': 'D004958'}, {'text': 'E2', 'type': 'Chemical', 'start': 1853, 'end': 1855, 'mesh': 'D004958'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 2013, 'end': 2021, 'mesh': 'D004967'}, {'text': 'tumor', 'type': 'Disease', 'start': 2030, 'end': 2035, 'mesh': 'D009369'}]"
+615,7604176,Pravastatin-associated myopathy. Report of a case.,"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.","[{'text': 'Pravastatin', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D017035'}, {'text': 'myopathy', 'type': 'Disease', 'start': 23, 'end': 31, 'mesh': 'D009135'}, {'text': 'inflammatory myopathy', 'type': 'Disease', 'start': 67, 'end': 88, 'mesh': 'D009220'}, {'text': 'pravastatin', 'type': 'Chemical', 'start': 116, 'end': 127, 'mesh': 'D017035'}, {'text': 'non-insulin-dependent diabetes mellitus', 'type': 'Disease', 'start': 266, 'end': 305, 'mesh': 'D003924'}, {'text': 'hypertension', 'type': 'Disease', 'start': 310, 'end': 322, 'mesh': 'D006973'}, {'text': 'pravastatin', 'type': 'Chemical', 'start': 335, 'end': 346, 'mesh': 'D017035'}, {'text': 'hypercholesterolemia', 'type': 'Disease', 'start': 370, 'end': 390, 'mesh': 'D006937'}, {'text': 'myopathy', 'type': 'Disease', 'start': 419, 'end': 427, 'mesh': 'D009135'}, {'text': 'pravastatin', 'type': 'Chemical', 'start': 482, 'end': 493, 'mesh': 'D017035'}, {'text': 'hypothyroidism', 'type': 'Disease', 'start': 532, 'end': 546, 'mesh': 'D007037'}, {'text': 'autoimmune thyroiditis', 'type': 'Disease', 'start': 572, 'end': 594, 'mesh': 'D013967'}, {'text': 'lovastatin', 'type': 'Chemical', 'start': 752, 'end': 762, 'mesh': 'D008148'}, {'text': 'simvastatin', 'type': 'Chemical', 'start': 767, 'end': 778, 'mesh': 'D019821'}, {'text': 'myopathy', 'type': 'Disease', 'start': 811, 'end': 819, 'mesh': 'D009135'}, {'text': 'pravastatin', 'type': 'Chemical', 'start': 821, 'end': 832, 'mesh': 'D017035'}, {'text': 'myopathy', 'type': 'Disease', 'start': 844, 'end': 852, 'mesh': 'D009135'}]"
+616,7282516,Dose-effect and structure-function relationships in doxorubicin cardiomyopathy.,"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.","[{'text': 'doxorubicin', 'type': 'Chemical', 'start': 52, 'end': 63, 'mesh': 'D004317'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 64, 'end': 78, 'mesh': 'D009202'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 84, 'end': 98, 'mesh': 'D009202'}, {'text': 'CM', 'type': 'Disease', 'start': 100, 'end': 102, 'mesh': 'D009202'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 136, 'end': 147, 'mesh': 'D004317'}, {'text': 'DXR', 'type': 'Chemical', 'start': 149, 'end': 152, 'mesh': 'D004317'}, {'text': 'Adriamycin', 'type': 'Chemical', 'start': 155, 'end': 165, 'mesh': 'D004317'}, {'text': 'myocardial disease', 'type': 'Disease', 'start': 279, 'end': 297, 'mesh': 'D009202'}, {'text': 'DXR', 'type': 'Chemical', 'start': 494, 'end': 497, 'mesh': 'D004317'}, {'text': 'DXR', 'type': 'Chemical', 'start': 576, 'end': 579, 'mesh': 'D004317'}, {'text': 'DXR', 'type': 'Chemical', 'start': 983, 'end': 986, 'mesh': 'D004317'}, {'text': 'CM', 'type': 'Disease', 'start': 987, 'end': 989, 'mesh': 'D009202'}, {'text': 'myocardial damage', 'type': 'Disease', 'start': 990, 'end': 1007, 'mesh': 'D009202'}, {'text': 'DXR', 'type': 'Chemical', 'start': 1059, 'end': 1062, 'mesh': 'D004317'}]"
+617,7072798,Fatal aplastic anemia following topical administration of ophthalmic chloramphenicol.,"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.","[{'text': 'aplastic anemia', 'type': 'Disease', 'start': 6, 'end': 21, 'mesh': 'D000741'}, {'text': 'chloramphenicol', 'type': 'Chemical', 'start': 69, 'end': 84, 'mesh': 'D002701'}, {'text': 'aplastic anemia', 'type': 'Disease', 'start': 114, 'end': 129, 'mesh': 'D000741'}, {'text': 'cataract', 'type': 'Disease', 'start': 168, 'end': 176, 'mesh': 'D002386'}, {'text': 'chloramphenicol', 'type': 'Chemical', 'start': 223, 'end': 238, 'mesh': 'D002701'}, {'text': 'pancytopenia', 'type': 'Disease', 'start': 259, 'end': 271, 'mesh': 'D010198'}, {'text': 'aplastic anemia', 'type': 'Disease', 'start': 330, 'end': 345, 'mesh': 'D000741'}, {'text': 'chloramphenicol', 'type': 'Chemical', 'start': 395, 'end': 410, 'mesh': 'D002701'}, {'text': 'aplastic anemia', 'type': 'Disease', 'start': 448, 'end': 463, 'mesh': 'D000741'}, {'text': 'chloramphenicol', 'type': 'Chemical', 'start': 493, 'end': 508, 'mesh': 'D002701'}, {'text': 'bone marrow hypoplasia', 'type': 'Disease', 'start': 565, 'end': 587, 'mesh': 'D001855'}, {'text': 'ocular toxicity', 'type': 'Disease', 'start': 642, 'end': 657, 'mesh': 'D005128'}, {'text': 'chloramphenicol', 'type': 'Chemical', 'start': 692, 'end': 707, 'mesh': 'D002701'}]"
+618,3769769,Bradycardia due to trihexyphenidyl hydrochloride.,"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.","[{'text': 'Bradycardia', 'type': 'Disease', 'start': 0, 'end': 11, 'mesh': 'D001919'}, {'text': 'trihexyphenidyl hydrochloride', 'type': 'Chemical', 'start': 19, 'end': 48, 'mesh': 'D014282'}, {'text': 'schizophrenic', 'type': 'Disease', 'start': 60, 'end': 73, 'mesh': 'D012559'}, {'text': 'trihexyphenidyl hydrochloride', 'type': 'Chemical', 'start': 124, 'end': 153, 'mesh': 'D014282'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 199, 'end': 210, 'mesh': 'D001919'}, {'text': 'trihexyphenidyl', 'type': 'Chemical', 'start': 241, 'end': 256, 'mesh': 'D014282'}, {'text': 'psychiatric', 'type': 'Disease', 'start': 349, 'end': 360, 'mesh': 'D001523'}]"
+619,3708922,Experimental cyclosporine nephrotoxicity: risk of concomitant chemotherapy.,"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.","[{'text': 'cyclosporine', 'type': 'Chemical', 'start': 13, 'end': 25, 'mesh': 'D016572'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 26, 'end': 40, 'mesh': 'D007674'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 88, 'end': 100, 'mesh': 'D016572'}, {'text': 'CSA', 'type': 'Chemical', 'start': 102, 'end': 105, 'mesh': 'D016572'}, {'text': 'renal toxicity', 'type': 'Disease', 'start': 184, 'end': 198, 'mesh': 'D007674'}, {'text': 'CSA', 'type': 'Chemical', 'start': 253, 'end': 256, 'mesh': 'D016572'}, {'text': 'CSA', 'type': 'Chemical', 'start': 381, 'end': 384, 'mesh': 'D016572'}, {'text': 'nephrotoxic', 'type': 'Disease', 'start': 427, 'end': 438, 'mesh': 'D007674'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 458, 'end': 468, 'mesh': 'D005839'}, {'text': 'amphothericin B', 'type': 'Chemical', 'start': 493, 'end': 508, 'mesh': 'D000666'}, {'text': 'ketoconazole', 'type': 'Chemical', 'start': 513, 'end': 525, 'mesh': 'D007654'}, {'text': 'CSA', 'type': 'Chemical', 'start': 605, 'end': 608, 'mesh': 'D016572'}, {'text': 'toxicity', 'type': 'Disease', 'start': 617, 'end': 625, 'mesh': 'D064420'}, {'text': 'Gentamicin', 'type': 'Chemical', 'start': 644, 'end': 654, 'mesh': 'D005839'}, {'text': 'CSA', 'type': 'Chemical', 'start': 690, 'end': 693, 'mesh': 'D016572'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 694, 'end': 708, 'mesh': 'D007674'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 720, 'end': 734, 'mesh': 'D007674'}, {'text': 'CSA', 'type': 'Chemical', 'start': 746, 'end': 749, 'mesh': 'D016572'}]"
+620,3220106,Receptor mechanisms of nicotine-induced locomotor hyperactivity in chronic nicotine-treated rats.,"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.","[{'text': 'nicotine', 'type': 'Chemical', 'start': 23, 'end': 31, 'mesh': 'D009538'}, {'text': 'locomotor hyperactivity', 'type': 'Disease', 'start': 40, 'end': 63, 'mesh': 'D006948'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 75, 'end': 83, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 134, 'end': 142, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 274, 'end': 282, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 428, 'end': 436, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 495, 'end': 503, 'mesh': 'D009538'}, {'text': 'spiperone', 'type': 'Chemical', 'start': 512, 'end': 521, 'mesh': 'D013134'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 579, 'end': 587, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 631, 'end': 639, 'mesh': 'D009538'}, {'text': 'spiperone', 'type': 'Chemical', 'start': 648, 'end': 657, 'mesh': 'D013134'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 697, 'end': 705, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 752, 'end': 760, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 813, 'end': 821, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 913, 'end': 921, 'mesh': 'D009538'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 962, 'end': 970, 'mesh': 'D004298'}, {'text': 'DA', 'type': 'Chemical', 'start': 972, 'end': 974, 'mesh': 'D004298'}, {'text': 'spiperone', 'type': 'Chemical', 'start': 1026, 'end': 1035, 'mesh': 'D013134'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 1095, 'end': 1103, 'mesh': 'D009538'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 1121, 'end': 1129, 'mesh': 'D009538'}, {'text': 'spiperone', 'type': 'Chemical', 'start': 1263, 'end': 1272, 'mesh': 'D013134'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 1325, 'end': 1333, 'mesh': 'D009538'}, {'text': 'DA', 'type': 'Chemical', 'start': 1365, 'end': 1367, 'mesh': 'D004298'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 1422, 'end': 1430, 'mesh': 'D009538'}, {'text': 'locomotor hyperactivity', 'type': 'Disease', 'start': 1452, 'end': 1475, 'mesh': 'D006948'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 1491, 'end': 1499, 'mesh': 'D009538'}, {'text': 'DA', 'type': 'Chemical', 'start': 1574, 'end': 1576, 'mesh': 'D004298'}, {'text': 'DA', 'type': 'Chemical', 'start': 1613, 'end': 1615, 'mesh': 'D004298'}]"
+621,2722224,Hydrocortisone-induced hypertension in humans: pressor responsiveness and sympathetic function.,"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)","[{'text': 'Hydrocortisone', 'type': 'Chemical', 'start': 0, 'end': 14, 'mesh': 'D006854'}, {'text': 'hypertension', 'type': 'Disease', 'start': 23, 'end': 35, 'mesh': 'D006973'}, {'text': 'hydrocortisone', 'type': 'Chemical', 'start': 101, 'end': 115, 'mesh': 'D006854'}, {'text': 'hydrocortisone', 'type': 'Chemical', 'start': 244, 'end': 258, 'mesh': 'D006854'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 369, 'end': 383, 'mesh': 'D009638'}, {'text': 'increased cardiac output', 'type': 'Disease', 'start': 600, 'end': 624, 'mesh': 'D016534'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 1129, 'end': 1143, 'mesh': 'D009638'}, {'text': 'hydrocortisone', 'type': 'Chemical', 'start': 1206, 'end': 1220, 'mesh': 'D006854'}, {'text': 'hydrocortisone', 'type': 'Chemical', 'start': 1320, 'end': 1334, 'mesh': 'D006854'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 1475, 'end': 1489, 'mesh': 'D009638'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 1530, 'end': 1544, 'mesh': 'D009638'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 1574, 'end': 1588, 'mesh': 'D009638'}, {'text': 'rise in resting blood pressure', 'type': 'Disease', 'start': 1686, 'end': 1716, 'mesh': 'D006973'}, {'text': 'hydrocortisone', 'type': 'Chemical', 'start': 1722, 'end': 1736, 'mesh': 'D006854'}, {'text': 'increased cardiac output', 'type': 'Disease', 'start': 1759, 'end': 1783, 'mesh': 'D016534'}]"
+622,1636026,Effects of suprofen on the isolated perfused rat kidney.,"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.","[{'text': 'suprofen', 'type': 'Chemical', 'start': 11, 'end': 19, 'mesh': 'D013496'}, {'text': 'suprofen', 'type': 'Chemical', 'start': 66, 'end': 74, 'mesh': 'D013496'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 119, 'end': 138, 'mesh': 'D058186'}, {'text': 'nephrotoxic', 'type': 'Disease', 'start': 221, 'end': 232, 'mesh': 'D007674'}, {'text': 'suprofen', 'type': 'Chemical', 'start': 270, 'end': 278, 'mesh': 'D013496'}, {'text': 'uric acid', 'type': 'Chemical', 'start': 408, 'end': 417, 'mesh': 'D014527'}, {'text': 'sodium', 'type': 'Chemical', 'start': 466, 'end': 472, 'mesh': 'D012964'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 484, 'end': 490, 'mesh': 'D010100'}, {'text': 'suprofen', 'type': 'Chemical', 'start': 551, 'end': 559, 'mesh': 'D013496'}, {'text': 'suprofen', 'type': 'Chemical', 'start': 705, 'end': 713, 'mesh': 'D013496'}, {'text': 'uric acid', 'type': 'Chemical', 'start': 742, 'end': 751, 'mesh': 'D014527'}, {'text': 'suprofen', 'type': 'Chemical', 'start': 780, 'end': 788, 'mesh': 'D013496'}, {'text': 'uric acid', 'type': 'Chemical', 'start': 807, 'end': 816, 'mesh': 'D014527'}, {'text': 'uric acid', 'type': 'Chemical', 'start': 875, 'end': 884, 'mesh': 'D014527'}, {'text': 'suprofen', 'type': 'Chemical', 'start': 909, 'end': 917, 'mesh': 'D013496'}, {'text': 'uric acid', 'type': 'Chemical', 'start': 990, 'end': 999, 'mesh': 'D014527'}, {'text': 'suprofen', 'type': 'Chemical', 'start': 1075, 'end': 1083, 'mesh': 'D013496'}, {'text': 'acute declines in renal function', 'type': 'Disease', 'start': 1091, 'end': 1123, 'mesh': 'D058186'}, {'text': 'uric acid', 'type': 'Chemical', 'start': 1189, 'end': 1198, 'mesh': 'D014527'}]"
+623,1610717,Cocaine-induced brainstem seizures and behavior.,"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.","[{'text': 'Cocaine', 'type': 'Chemical', 'start': 0, 'end': 7, 'mesh': 'D003042'}, {'text': 'seizures', 'type': 'Disease', 'start': 26, 'end': 34, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 319, 'end': 326, 'mesh': 'D003042'}, {'text': 'Cocaine', 'type': 'Chemical', 'start': 481, 'end': 488, 'mesh': 'D003042'}, {'text': 'Cocaine', 'type': 'Chemical', 'start': 625, 'end': 632, 'mesh': 'D003042'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 804, 'end': 817, 'mesh': 'D006948'}, {'text': 'hypersensitivity', 'type': 'Disease', 'start': 819, 'end': 835, 'mesh': 'D004342'}, {'text': 'Hypersensitivity', 'type': 'Disease', 'start': 1068, 'end': 1084, 'mesh': 'D004342'}, {'text': 'Cocaine', 'type': 'Chemical', 'start': 1414, 'end': 1421, 'mesh': 'D003042'}]"
+624,873132,Increased sulfation and decreased 7alpha-hydroxylation of deoxycholic acid in ethinyl estradiol-induced cholestasis in rats.,"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.","[{'text': 'deoxycholic acid', 'type': 'Chemical', 'start': 58, 'end': 74, 'mesh': 'D003840'}, {'text': 'ethinyl estradiol', 'type': 'Chemical', 'start': 78, 'end': 95, 'mesh': 'D004997'}, {'text': 'cholestasis', 'type': 'Disease', 'start': 104, 'end': 115, 'mesh': 'D002779'}, {'text': 'Deoxycholic acid', 'type': 'Chemical', 'start': 125, 'end': 141, 'mesh': 'D003840'}, {'text': 'ethinyl estradiol', 'type': 'Chemical', 'start': 219, 'end': 236, 'mesh': 'D004997'}, {'text': 'deoxycholic acid', 'type': 'Chemical', 'start': 313, 'end': 329, 'mesh': 'D003840'}, {'text': 'taurodeoxycholic acid', 'type': 'Chemical', 'start': 335, 'end': 356, 'mesh': 'D013657'}, {'text': 'ethinyl estradiol', 'type': 'Chemical', 'start': 385, 'end': 402, 'mesh': 'D004997'}, {'text': 'sodium deoxycholate', 'type': 'Chemical', 'start': 429, 'end': 448, 'mesh': 'D003840'}, {'text': 'bile acid', 'type': 'Chemical', 'start': 472, 'end': 481, 'mesh': 'D001647'}, {'text': 'ethinyl estradiol', 'type': 'Chemical', 'start': 567, 'end': 584, 'mesh': 'D004997'}, {'text': 'Ethinyl estradiol', 'type': 'Chemical', 'start': 599, 'end': 616, 'mesh': 'D004997'}, {'text': 'taurocholic acid', 'type': 'Chemical', 'start': 668, 'end': 684, 'mesh': 'D013656'}, {'text': 'taurodeoxycholic acid', 'type': 'Chemical', 'start': 768, 'end': 789, 'mesh': 'D013657'}, {'text': 'Ethinyl estradiol', 'type': 'Chemical', 'start': 791, 'end': 808, 'mesh': 'D004997'}, {'text': 'deoxycholic acid', 'type': 'Chemical', 'start': 849, 'end': 865, 'mesh': 'D003840'}, {'text': 'taurodeoxycholic acid', 'type': 'Chemical', 'start': 913, 'end': 934, 'mesh': 'D013657'}, {'text': 'deoxycholic acid', 'type': 'Chemical', 'start': 1081, 'end': 1097, 'mesh': 'D003840'}, {'text': 'deoxycholic acid', 'type': 'Chemical', 'start': 1159, 'end': 1175, 'mesh': 'D003840'}, {'text': 'taurocholic acid', 'type': 'Chemical', 'start': 1199, 'end': 1215, 'mesh': 'D013656'}, {'text': 'ethinyl estradiol', 'type': 'Chemical', 'start': 1274, 'end': 1291, 'mesh': 'D004997'}, {'text': 'bile acid', 'type': 'Chemical', 'start': 1393, 'end': 1402, 'mesh': 'D001647'}]"
+625,783197,"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.","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.","[{'text': 'ouabain', 'type': 'Chemical', 'start': 11, 'end': 18, 'mesh': 'D010042'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 33, 'end': 39, 'mesh': 'D010100'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 83, 'end': 106, 'mesh': 'D003324'}, {'text': 'heart failure', 'type': 'Disease', 'start': 175, 'end': 188, 'mesh': 'D006333'}, {'text': 'digitalis glycosides', 'type': 'Chemical', 'start': 205, 'end': 225, 'mesh': 'D004071'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 240, 'end': 246, 'mesh': 'D010100'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 323, 'end': 346, 'mesh': 'D003324'}, {'text': 'ouabain', 'type': 'Chemical', 'start': 421, 'end': 428, 'mesh': 'D010042'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 543, 'end': 566, 'mesh': 'D003324'}, {'text': 'congestive heart failure', 'type': 'Disease', 'start': 584, 'end': 608, 'mesh': 'D006333'}, {'text': 'ouabain', 'type': 'Chemical', 'start': 779, 'end': 786, 'mesh': 'D010042'}, {'text': 'ouabain', 'type': 'Chemical', 'start': 924, 'end': 931, 'mesh': 'D010042'}, {'text': 'ouabain', 'type': 'Chemical', 'start': 1215, 'end': 1222, 'mesh': 'D010042'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 1550, 'end': 1556, 'mesh': 'D010100'}, {'text': 'ouabain', 'type': 'Chemical', 'start': 1584, 'end': 1591, 'mesh': 'D010042'}, {'text': 'ouabain', 'type': 'Chemical', 'start': 1686, 'end': 1693, 'mesh': 'D010042'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 1775, 'end': 1798, 'mesh': 'D003324'}, {'text': 'congestive heart failure', 'type': 'Disease', 'start': 1823, 'end': 1847, 'mesh': 'D006333'}, {'text': 'left ventricular end-diastolic volume falls', 'type': 'Disease', 'start': 1848, 'end': 1891, 'mesh': 'D002303'}, {'text': 'ouabain', 'type': 'Chemical', 'start': 1898, 'end': 1905, 'mesh': 'D010042'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 2055, 'end': 2061, 'mesh': 'D010100'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 2153, 'end': 2159, 'mesh': 'D010100'}]"
+626,9545159,Prolongation of the QT interval related to cisapride-diltiazem interaction.,"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.","[{'text': 'Prolongation of the QT interval', 'type': 'Disease', 'start': 0, 'end': 31, 'mesh': 'D008133'}, {'text': 'cisapride', 'type': 'Chemical', 'start': 43, 'end': 52, 'mesh': 'D020117'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 53, 'end': 62, 'mesh': 'D004110'}, {'text': 'Cisapride', 'type': 'Chemical', 'start': 76, 'end': 85, 'mesh': 'D020117'}, {'text': 'gastrointestinal motility disorders', 'type': 'Disease', 'start': 171, 'end': 206, 'mesh': 'D015835'}, {'text': 'Prolongation of QT interval', 'type': 'Disease', 'start': 208, 'end': 235, 'mesh': 'D008133'}, {'text': 'torsades de pointes', 'type': 'Disease', 'start': 237, 'end': 256, 'mesh': 'D016171'}, {'text': 'sudden cardiac death', 'type': 'Disease', 'start': 262, 'end': 282, 'mesh': 'D016757'}, {'text': 'erythromycin', 'type': 'Chemical', 'start': 340, 'end': 352, 'mesh': 'D004917'}, {'text': 'azole', 'type': 'Chemical', 'start': 356, 'end': 361, 'mesh': 'D001393'}, {'text': 'cisapride', 'type': 'Chemical', 'start': 494, 'end': 503, 'mesh': 'D020117'}, {'text': 'gastroesophageal reflux disorder', 'type': 'Disease', 'start': 508, 'end': 540, 'mesh': 'D005764'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 545, 'end': 554, 'mesh': 'D004110'}, {'text': 'hypertension', 'type': 'Disease', 'start': 607, 'end': 619, 'mesh': 'D006973'}, {'text': 'syncope', 'type': 'Disease', 'start': 645, 'end': 652, 'mesh': 'D013575'}, {'text': 'QT-interval prolongation', 'type': 'Disease', 'start': 661, 'end': 685, 'mesh': 'D008133'}, {'text': 'cisapride', 'type': 'Chemical', 'start': 707, 'end': 716, 'mesh': 'D020117'}, {'text': 'cisapride', 'type': 'Chemical', 'start': 819, 'end': 828, 'mesh': 'D020117'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 890, 'end': 899, 'mesh': 'D004110'}]"
+627,8643973,Paclitaxel combined with carboplatin in the first-line treatment of advanced ovarian cancer.,"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.","[{'text': 'Paclitaxel', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D017239'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 25, 'end': 36, 'mesh': 'D016190'}, {'text': 'ovarian cancer', 'type': 'Disease', 'start': 77, 'end': 91, 'mesh': 'D010051'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 155, 'end': 165, 'mesh': 'D017239'}, {'text': 'Taxol', 'type': 'Chemical', 'start': 167, 'end': 172, 'mesh': 'D017239'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 266, 'end': 277, 'mesh': 'D016190'}, {'text': 'ovarian cancer', 'type': 'Disease', 'start': 328, 'end': 342, 'mesh': 'D010051'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 344, 'end': 354, 'mesh': 'D017239'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 489, 'end': 500, 'mesh': 'D016190'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 647, 'end': 658, 'mesh': 'D016190'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 735, 'end': 745, 'mesh': 'D017239'}, {'text': 'toxicity', 'type': 'Disease', 'start': 948, 'end': 956, 'mesh': 'D064420'}, {'text': 'myelosuppression', 'type': 'Disease', 'start': 980, 'end': 996, 'mesh': 'D001855'}, {'text': 'leukopenia', 'type': 'Disease', 'start': 998, 'end': 1008, 'mesh': 'D007970'}, {'text': 'granulocytopenia', 'type': 'Disease', 'start': 1010, 'end': 1026, 'mesh': 'D000380'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 1032, 'end': 1048, 'mesh': 'D013921'}, {'text': 'Neurotoxicity', 'type': 'Disease', 'start': 1051, 'end': 1064, 'mesh': 'D020258'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 1317, 'end': 1327, 'mesh': 'D017239'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 1417, 'end': 1428, 'mesh': 'D016190'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 1565, 'end': 1575, 'mesh': 'D017239'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 1590, 'end': 1601, 'mesh': 'D016190'}]"
+628,10743694,Treatment of tacrolimus-related adverse effects by conversion to cyclosporine in liver transplant recipients.,"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.","[{'text': 'tacrolimus', 'type': 'Chemical', 'start': 13, 'end': 23, 'mesh': 'D016559'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 65, 'end': 77, 'mesh': 'D016572'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 115, 'end': 125, 'mesh': 'D016559'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 185, 'end': 197, 'mesh': 'D016572'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 259, 'end': 269, 'mesh': 'D016559'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 395, 'end': 405, 'mesh': 'D016559'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 566, 'end': 576, 'mesh': 'D016559'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 771, 'end': 784, 'mesh': 'D020258'}, {'text': '(insulin-dependent) diabetes mellitus', 'type': 'Disease', 'start': 791, 'end': 828, 'mesh': 'D003922'}, {'text': 'IDDM', 'type': 'Disease', 'start': 830, 'end': 834, 'mesh': 'D003922'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 841, 'end': 855, 'mesh': 'D007674'}, {'text': 'gastrointestinal (GI) toxicity', 'type': 'Disease', 'start': 861, 'end': 891, 'mesh': 'D005767'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 901, 'end': 915, 'mesh': 'D009202'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 950, 'end': 963, 'mesh': 'D020258'}, {'text': 'IDDM', 'type': 'Disease', 'start': 970, 'end': 974, 'mesh': 'D003922'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 981, 'end': 995, 'mesh': 'D007674'}, {'text': 'GI toxicity', 'type': 'Disease', 'start': 1001, 'end': 1012, 'mesh': 'D005767'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 1018, 'end': 1032, 'mesh': 'D056486'}, {'text': 'post-transplant lmphoproliferate disease', 'type': 'Disease', 'start': 1038, 'end': 1078, 'mesh': 'D008232'}, {'text': 'PTLD', 'type': 'Disease', 'start': 1080, 'end': 1084, 'mesh': 'D008232'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 1091, 'end': 1105, 'mesh': 'D009202'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 1111, 'end': 1127, 'mesh': 'D000743'}, {'text': 'pruritus', 'type': 'Disease', 'start': 1137, 'end': 1145, 'mesh': 'D011537'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 1495, 'end': 1505, 'mesh': 'D016559'}]"
+629,3535719,Relative efficacy and toxicity of netilmicin and tobramycin in oncology patients.,"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.","[{'text': 'toxicity', 'type': 'Disease', 'start': 22, 'end': 30, 'mesh': 'D064420'}, {'text': 'netilmicin', 'type': 'Chemical', 'start': 34, 'end': 44, 'mesh': 'D009428'}, {'text': 'tobramycin', 'type': 'Chemical', 'start': 49, 'end': 59, 'mesh': 'D014031'}, {'text': 'netilmicin sulfate', 'type': 'Chemical', 'start': 135, 'end': 153, 'mesh': 'D009428'}, {'text': 'tobramycin sulfate', 'type': 'Chemical', 'start': 157, 'end': 175, 'mesh': 'D014031'}, {'text': 'piperacillin sodium', 'type': 'Chemical', 'start': 196, 'end': 215, 'mesh': 'D010878'}, {'text': 'infections', 'type': 'Disease', 'start': 271, 'end': 281, 'mesh': 'D007239'}, {'text': 'Nephrotoxicity', 'type': 'Disease', 'start': 336, 'end': 350, 'mesh': 'D007674'}, {'text': 'netilmicin', 'type': 'Chemical', 'start': 409, 'end': 419, 'mesh': 'D009428'}, {'text': 'tobramycin', 'type': 'Chemical', 'start': 424, 'end': 434, 'mesh': 'D014031'}, {'text': 'Ototoxicity', 'type': 'Disease', 'start': 449, 'end': 460, 'mesh': 'D006311'}, {'text': 'netilmicin', 'type': 'Chemical', 'start': 491, 'end': 501, 'mesh': 'D009428'}, {'text': 'piperacillin', 'type': 'Chemical', 'start': 506, 'end': 518, 'mesh': 'D010878'}, {'text': 'tobramycin', 'type': 'Chemical', 'start': 541, 'end': 551, 'mesh': 'D014031'}, {'text': 'piperacillin', 'type': 'Chemical', 'start': 556, 'end': 568, 'mesh': 'D010878'}, {'text': 'netilmicin', 'type': 'Chemical', 'start': 649, 'end': 659, 'mesh': 'D009428'}, {'text': 'piperacillin', 'type': 'Chemical', 'start': 664, 'end': 676, 'mesh': 'D010878'}, {'text': 'tobramycin', 'type': 'Chemical', 'start': 763, 'end': 773, 'mesh': 'D014031'}, {'text': 'piperacillin', 'type': 'Chemical', 'start': 778, 'end': 790, 'mesh': 'D010878'}, {'text': 'netilmicin', 'type': 'Chemical', 'start': 1003, 'end': 1013, 'mesh': 'D009428'}, {'text': 'piperacillin', 'type': 'Chemical', 'start': 1018, 'end': 1030, 'mesh': 'D010878'}, {'text': 'tobramycin', 'type': 'Chemical', 'start': 1035, 'end': 1045, 'mesh': 'D014031'}, {'text': 'piperacillin', 'type': 'Chemical', 'start': 1050, 'end': 1062, 'mesh': 'D010878'}, {'text': 'aminoglycoside', 'type': 'Chemical', 'start': 1122, 'end': 1136, 'mesh': 'D000617'}, {'text': 'ototoxicity', 'type': 'Disease', 'start': 1148, 'end': 1159, 'mesh': 'D006311'}, {'text': 'netilmicin', 'type': 'Chemical', 'start': 1207, 'end': 1217, 'mesh': 'D009428'}, {'text': 'tobramycin', 'type': 'Chemical', 'start': 1228, 'end': 1238, 'mesh': 'D014031'}]"
+630,6433367,Effect of prostaglandin synthetase inhibitors on experimentally induced convulsions in rats.,"To investigate the relationship of prostaglandins (PGs) to seizure induction, the effects of six PG synthetase inhibitors on convulsions induced by flurothyl, picrotoxin, pentetrazol (PTZ), electroshock or bicuculline were evaluated. Ibuprofen, sulindac, mefenamic acid, and low dose meclofenamic acid increased the latency-to-onset in the flurothyl and/or PTZ models; the electroshock, picrotoxin and bicuculline models were not significantly affected by any of the pretreatment agents. 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.","[{'text': 'prostaglandin', 'type': 'Chemical', 'start': 10, 'end': 23, 'mesh': 'D011453'}, {'text': 'convulsions', 'type': 'Disease', 'start': 72, 'end': 83, 'mesh': 'D012640'}, {'text': 'prostaglandins', 'type': 'Chemical', 'start': 128, 'end': 142, 'mesh': 'D011453'}, {'text': 'PGs', 'type': 'Chemical', 'start': 144, 'end': 147, 'mesh': 'D011453'}, {'text': 'seizure', 'type': 'Disease', 'start': 152, 'end': 159, 'mesh': 'D012640'}, {'text': 'convulsions', 'type': 'Disease', 'start': 218, 'end': 229, 'mesh': 'D012640'}, {'text': 'flurothyl', 'type': 'Chemical', 'start': 241, 'end': 250, 'mesh': 'D005481'}, {'text': 'picrotoxin', 'type': 'Chemical', 'start': 252, 'end': 262, 'mesh': 'D010852'}, {'text': 'pentetrazol', 'type': 'Chemical', 'start': 264, 'end': 275, 'mesh': 'D010433'}, {'text': 'PTZ', 'type': 'Chemical', 'start': 277, 'end': 280, 'mesh': 'D010433'}, {'text': 'bicuculline', 'type': 'Chemical', 'start': 299, 'end': 310, 'mesh': 'D001640'}, {'text': 'Ibuprofen', 'type': 'Chemical', 'start': 327, 'end': 336, 'mesh': 'D007052'}, {'text': 'sulindac', 'type': 'Chemical', 'start': 338, 'end': 346, 'mesh': 'D013467'}, {'text': 'mefenamic acid', 'type': 'Chemical', 'start': 348, 'end': 362, 'mesh': 'D008528'}, {'text': 'meclofenamic acid', 'type': 'Chemical', 'start': 377, 'end': 394, 'mesh': 'D008469'}, {'text': 'flurothyl', 'type': 'Chemical', 'start': 433, 'end': 442, 'mesh': 'D005481'}, {'text': 'PTZ', 'type': 'Chemical', 'start': 450, 'end': 453, 'mesh': 'D010433'}, {'text': 'picrotoxin', 'type': 'Chemical', 'start': 480, 'end': 490, 'mesh': 'D010852'}, {'text': 'bicuculline', 'type': 'Chemical', 'start': 495, 'end': 506, 'mesh': 'D001640'}, {'text': 'PGs', 'type': 'Chemical', 'start': 608, 'end': 611, 'mesh': 'D011453'}, {'text': 'fluorthyl', 'type': 'Chemical', 'start': 656, 'end': 665, 'mesh': 'D005481'}, {'text': 'PTZ', 'type': 'Chemical', 'start': 671, 'end': 674, 'mesh': 'D010433'}, {'text': 'convulsions', 'type': 'Disease', 'start': 683, 'end': 694, 'mesh': 'D012640'}, {'text': 'picrotoxin', 'type': 'Chemical', 'start': 704, 'end': 714, 'mesh': 'D010852'}, {'text': 'bicuculline', 'type': 'Chemical', 'start': 735, 'end': 746, 'mesh': 'D001640'}, {'text': 'convulsions', 'type': 'Disease', 'start': 755, 'end': 766, 'mesh': 'D012640'}]"
+631,17285209,Angiotensin-converting enzyme (ACE) inhibitor-associated angioedema of the stomach and small intestine: a case report.,"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.","[{'text': 'angioedema', 'type': 'Disease', 'start': 57, 'end': 67, 'mesh': 'D000799'}, {'text': 'hypertension', 'type': 'Disease', 'start': 203, 'end': 215, 'mesh': 'D006973'}, {'text': 'amlodipine', 'type': 'Chemical', 'start': 258, 'end': 268, 'mesh': 'D017311'}, {'text': 'benazapril', 'type': 'Chemical', 'start': 269, 'end': 279, 'mesh': 'C044946'}, {'text': 'abdominal pain', 'type': 'Disease', 'start': 354, 'end': 368, 'mesh': 'D015746'}, {'text': 'nausea', 'type': 'Disease', 'start': 370, 'end': 376, 'mesh': 'D009325'}, {'text': 'vomiting', 'type': 'Disease', 'start': 381, 'end': 389, 'mesh': 'D014839'}, {'text': 'angioedema', 'type': 'Disease', 'start': 932, 'end': 942, 'mesh': 'D000799'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 967, 'end': 979, 'mesh': 'D006973'}, {'text': 'ascites', 'type': 'Disease', 'start': 1172, 'end': 1179, 'mesh': 'D001201'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 1200, 'end': 1211, 'mesh': 'D000809'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 1240, 'end': 1251, 'mesh': 'D000809'}]"
+632,15858223,"Valproic acid I: time course of lipid peroxidation biomarkers, liver toxicity, and valproic acid metabolite levels in rats.","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.","[{'text': 'Valproic acid', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'D014635'}, {'text': 'liver toxicity', 'type': 'Disease', 'start': 63, 'end': 77, 'mesh': 'D056486'}, {'text': 'valproic acid', 'type': 'Chemical', 'start': 83, 'end': 96, 'mesh': 'D014635'}, {'text': 'valproic acid', 'type': 'Chemical', 'start': 141, 'end': 154, 'mesh': 'D014635'}, {'text': 'VPA', 'type': 'Chemical', 'start': 156, 'end': 159, 'mesh': 'D014635'}, {'text': '15-F(2t)-isoprostane', 'type': 'Chemical', 'start': 297, 'end': 317, 'mesh': 'C075750'}, {'text': '15-F(2t)-IsoP', 'type': 'Chemical', 'start': 319, 'end': 332, 'mesh': 'C075750'}, {'text': 'VPA', 'type': 'Chemical', 'start': 398, 'end': 401, 'mesh': 'D014635'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 434, 'end': 448, 'mesh': 'D056486'}, {'text': 'VPA', 'type': 'Chemical', 'start': 502, 'end': 505, 'mesh': 'D014635'}, {'text': '15-F(2t)-IsoP', 'type': 'Chemical', 'start': 655, 'end': 668, 'mesh': 'C075750'}, {'text': 'lipid hydroperoxides', 'type': 'Chemical', 'start': 670, 'end': 690, 'mesh': 'D008054'}, {'text': 'LPO', 'type': 'Chemical', 'start': 692, 'end': 695, 'mesh': 'D008054'}, {'text': 'thiobarbituric acid reactive substances', 'type': 'Chemical', 'start': 702, 'end': 741, 'mesh': 'D017392'}, {'text': 'TBARs', 'type': 'Chemical', 'start': 743, 'end': 748, 'mesh': 'D017392'}, {'text': '15-F(2t)-IsoP', 'type': 'Chemical', 'start': 768, 'end': 781, 'mesh': 'C075750'}, {'text': 'VPA', 'type': 'Chemical', 'start': 833, 'end': 836, 'mesh': 'D014635'}, {'text': 'LPO', 'type': 'Chemical', 'start': 874, 'end': 877, 'mesh': 'D008054'}, {'text': 'TBARs', 'type': 'Chemical', 'start': 982, 'end': 987, 'mesh': 'D017392'}, {'text': 'Liver toxicity', 'type': 'Disease', 'start': 1053, 'end': 1067, 'mesh': 'D056486'}, {'text': 'glutathione', 'type': 'Chemical', 'start': 1113, 'end': 1124, 'mesh': 'D005978'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 1252, 'end': 1266, 'mesh': 'D056486'}, {'text': 'inflammation', 'type': 'Disease', 'start': 1307, 'end': 1319, 'mesh': 'D007249'}, {'text': 'necrosis', 'type': 'Disease', 'start': 1342, 'end': 1350, 'mesh': 'D009336'}, {'text': 'steatosis', 'type': 'Disease', 'start': 1356, 'end': 1365, 'mesh': 'D005234'}, {'text': 'VPA', 'type': 'Chemical', 'start': 1438, 'end': 1441, 'mesh': 'D014635'}, {'text': '4-ene-VPA', 'type': 'Chemical', 'start': 1488, 'end': 1497, 'mesh': 'C045022'}, {'text': '2,4-diene-VPA', 'type': 'Chemical', 'start': 1506, 'end': 1519, 'mesh': 'C556631'}, {'text': 'VPA', 'type': 'Chemical', 'start': 1598, 'end': 1601, 'mesh': 'D014635'}, {'text': '15-F(2t)-IsoP', 'type': 'Chemical', 'start': 1666, 'end': 1679, 'mesh': 'C075750'}, {'text': 'necrosis', 'type': 'Disease', 'start': 1709, 'end': 1717, 'mesh': 'D009336'}, {'text': 'steatosis', 'type': 'Disease', 'start': 1719, 'end': 1728, 'mesh': 'D005234'}]"
+633,15811908,Pheochromocytoma unmasked by amisulpride and tiapride.,"OBJECTIVE: To describe the unmasking of pheochromocytoma in a patient treated with amisulpride and tiapride. CASE SUMMARY: A 42-year-old white man developed acute hypertension with severe headache and vomiting 2 hours after the first doses of amisulpride 100 mg and tiapride 100 mg. Both drugs were immediately discontinued, and the patient recovered after subsequent nicardipine and verapamil treatment. Abdominal ultrasound showed an adrenal mass, and postoperative histologic examination confirmed the diagnosis of pheochromocytoma. DISCUSSION: Drug-induced symptoms of pheochromocytoma are often associated with the use of substituted benzamide drugs, but the underlying mechanism is unknown. 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 amisulpride.","[{'text': 'Pheochromocytoma', 'type': 'Disease', 'start': 0, 'end': 16, 'mesh': 'D010673'}, {'text': 'amisulpride', 'type': 'Chemical', 'start': 29, 'end': 40, 'mesh': 'C012052'}, {'text': 'tiapride', 'type': 'Chemical', 'start': 45, 'end': 53, 'mesh': 'D063325'}, {'text': 'pheochromocytoma', 'type': 'Disease', 'start': 95, 'end': 111, 'mesh': 'D010673'}, {'text': 'amisulpride', 'type': 'Chemical', 'start': 138, 'end': 149, 'mesh': 'C012052'}, {'text': 'tiapride', 'type': 'Chemical', 'start': 154, 'end': 162, 'mesh': 'D063325'}, {'text': 'hypertension', 'type': 'Disease', 'start': 218, 'end': 230, 'mesh': 'D006973'}, {'text': 'headache', 'type': 'Disease', 'start': 243, 'end': 251, 'mesh': 'D006261'}, {'text': 'vomiting', 'type': 'Disease', 'start': 256, 'end': 264, 'mesh': 'D014839'}, {'text': 'amisulpride', 'type': 'Chemical', 'start': 298, 'end': 309, 'mesh': 'C012052'}, {'text': 'tiapride', 'type': 'Chemical', 'start': 321, 'end': 329, 'mesh': 'D063325'}, {'text': 'nicardipine', 'type': 'Chemical', 'start': 423, 'end': 434, 'mesh': 'D009529'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 439, 'end': 448, 'mesh': 'D014700'}, {'text': 'pheochromocytoma', 'type': 'Disease', 'start': 573, 'end': 589, 'mesh': 'D010673'}, {'text': 'pheochromocytoma', 'type': 'Disease', 'start': 628, 'end': 644, 'mesh': 'D010673'}, {'text': 'benzamide', 'type': 'Chemical', 'start': 694, 'end': 703, 'mesh': 'C037689'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 848, 'end': 860, 'mesh': 'D006973'}, {'text': 'amisulpride', 'type': 'Chemical', 'start': 872, 'end': 883, 'mesh': 'C012052'}, {'text': 'tiapride', 'type': 'Chemical', 'start': 888, 'end': 896, 'mesh': 'D063325'}, {'text': 'amisulpride', 'type': 'Chemical', 'start': 976, 'end': 987, 'mesh': 'C012052'}, {'text': 'tiapride', 'type': 'Chemical', 'start': 993, 'end': 1001, 'mesh': 'D063325'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 1010, 'end': 1022, 'mesh': 'D006973'}, {'text': 'pheochromocytoma', 'type': 'Disease', 'start': 1048, 'end': 1064, 'mesh': 'D010673'}, {'text': 'tiapride', 'type': 'Chemical', 'start': 1164, 'end': 1172, 'mesh': 'D063325'}, {'text': 'amisulpride', 'type': 'Chemical', 'start': 1177, 'end': 1188, 'mesh': 'C012052'}]"
+634,15764424,"Quantitative drug levels in stimulant psychosis: relationship to symptom severity, catecholamines and hyperkinesia.","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.","[{'text': 'psychosis', 'type': 'Disease', 'start': 38, 'end': 47, 'mesh': 'D011605'}, {'text': 'catecholamines', 'type': 'Chemical', 'start': 83, 'end': 97, 'mesh': 'D002395'}, {'text': 'hyperkinesia', 'type': 'Disease', 'start': 102, 'end': 114, 'mesh': 'D006948'}, {'text': 'catecholamines', 'type': 'Chemical', 'start': 188, 'end': 202, 'mesh': 'D002395'}, {'text': 'psychotic symptoms', 'type': 'Disease', 'start': 208, 'end': 226, 'mesh': 'D011605'}, {'text': 'psychiatric', 'type': 'Disease', 'start': 251, 'end': 262, 'mesh': 'D001523'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 301, 'end': 312, 'mesh': 'D000661'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 317, 'end': 324, 'mesh': 'D003042'}, {'text': 'psychosis', 'type': 'Disease', 'start': 333, 'end': 342, 'mesh': 'D011605'}, {'text': 'catecholamine', 'type': 'Chemical', 'start': 443, 'end': 456, 'mesh': 'D002395'}, {'text': 'Methamphetamine', 'type': 'Chemical', 'start': 476, 'end': 491, 'mesh': 'D008694'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 495, 'end': 506, 'mesh': 'D000661'}, {'text': 'hyperkinesia', 'type': 'Disease', 'start': 576, 'end': 588, 'mesh': 'D006948'}, {'text': 'hyperkinesia', 'type': 'Disease', 'start': 631, 'end': 643, 'mesh': 'D006948'}, {'text': 'psychotic symptoms', 'type': 'Disease', 'start': 778, 'end': 796, 'mesh': 'D011605'}, {'text': 'stereotypies', 'type': 'Disease', 'start': 801, 'end': 813, 'mesh': 'D019956'}]"
+635,12101159,Delayed asystolic cardiac arrest after diltiazem overdose; resuscitation with high dose intravenous calcium.,"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.","[{'text': 'asystolic', 'type': 'Disease', 'start': 8, 'end': 17, 'mesh': 'D006323'}, {'text': 'cardiac arrest', 'type': 'Disease', 'start': 18, 'end': 32, 'mesh': 'D006323'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 39, 'end': 48, 'mesh': 'D004110'}, {'text': 'overdose', 'type': 'Disease', 'start': 49, 'end': 57, 'mesh': 'D062787'}, {'text': 'calcium', 'type': 'Chemical', 'start': 100, 'end': 107, 'mesh': 'D002118'}, {'text': 'overdose', 'type': 'Disease', 'start': 140, 'end': 148, 'mesh': 'D062787'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 172, 'end': 181, 'mesh': 'D004110'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 183, 'end': 194, 'mesh': 'D000082'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 196, 'end': 203, 'mesh': 'D001241'}, {'text': 'isosorbide', 'type': 'Chemical', 'start': 205, 'end': 215, 'mesh': 'D007547'}, {'text': 'nitrate', 'type': 'Chemical', 'start': 216, 'end': 223, 'mesh': 'D009566'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 229, 'end': 236, 'mesh': 'D000431'}, {'text': 'hypotension', 'type': 'Disease', 'start': 299, 'end': 310, 'mesh': 'D007022'}, {'text': 'overdose', 'type': 'Disease', 'start': 400, 'end': 408, 'mesh': 'D062787'}, {'text': 'tonic-clonic seizures', 'type': 'Disease', 'start': 432, 'end': 453, 'mesh': 'D004830'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 505, 'end': 516, 'mesh': 'D001919'}, {'text': 'asystolic', 'type': 'Disease', 'start': 563, 'end': 572, 'mesh': 'D006323'}, {'text': 'calcium', 'type': 'Chemical', 'start': 630, 'end': 637, 'mesh': 'D002118'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 642, 'end': 652, 'mesh': 'D004837'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 654, 'end': 665, 'mesh': 'D004837'}, {'text': 'calcium', 'type': 'Chemical', 'start': 815, 'end': 822, 'mesh': 'D002118'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 841, 'end': 850, 'mesh': 'D004110'}, {'text': 'overdose', 'type': 'Disease', 'start': 851, 'end': 859, 'mesh': 'D062787'}, {'text': 'asystole', 'type': 'Disease', 'start': 892, 'end': 900, 'mesh': 'D006323'}, {'text': 'cardiac arrest', 'type': 'Disease', 'start': 944, 'end': 958, 'mesh': 'D006323'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 965, 'end': 974, 'mesh': 'D004110'}, {'text': 'overdose', 'type': 'Disease', 'start': 975, 'end': 983, 'mesh': 'D062787'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1036, 'end': 1044, 'mesh': 'D064420'}]"
+636,6699841,Renal papillary necrosis due to naproxen.,"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.","[{'text': 'Renal papillary necrosis', 'type': 'Disease', 'start': 0, 'end': 24, 'mesh': 'D007681'}, {'text': 'naproxen', 'type': 'Chemical', 'start': 32, 'end': 40, 'mesh': 'D009288'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 65, 'end': 85, 'mesh': 'D001172'}, {'text': 'sulindac', 'type': 'Chemical', 'start': 124, 'end': 132, 'mesh': 'D013467'}, {'text': 'fenoprofen calcium', 'type': 'Chemical', 'start': 134, 'end': 152, 'mesh': 'D005279'}, {'text': 'salicylates', 'type': 'Chemical', 'start': 164, 'end': 175, 'mesh': 'D012459'}, {'text': 'gold', 'type': 'Chemical', 'start': 180, 'end': 184, 'mesh': 'D006046'}, {'text': 'renal papillary necrosis', 'type': 'Disease', 'start': 202, 'end': 226, 'mesh': 'D007681'}, {'text': 'RPN', 'type': 'Disease', 'start': 228, 'end': 231, 'mesh': 'D007681'}, {'text': 'naproxen', 'type': 'Chemical', 'start': 263, 'end': 271, 'mesh': 'D009288'}, {'text': 'RPN', 'type': 'Disease', 'start': 313, 'end': 316, 'mesh': 'D007681'}, {'text': 'Sulindac', 'type': 'Chemical', 'start': 338, 'end': 346, 'mesh': 'D013467'}, {'text': 'naproxen', 'type': 'Chemical', 'start': 367, 'end': 375, 'mesh': 'D009288'}, {'text': 'RPN', 'type': 'Disease', 'start': 482, 'end': 485, 'mesh': 'D007681'}, {'text': 'sulindac', 'type': 'Chemical', 'start': 550, 'end': 558, 'mesh': 'D013467'}, {'text': 'renal toxicity', 'type': 'Disease', 'start': 592, 'end': 606, 'mesh': 'D007674'}]"
+637,6127992,Adverse interaction between beta-adrenergic blocking drugs and verapamil--report of three cases.,"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.","[{'text': 'beta-adrenergic blocking drugs', 'type': 'Chemical', 'start': 28, 'end': 58, 'mesh': 'D000319'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 63, 'end': 72, 'mesh': 'D014700'}, {'text': 'ischaemic heart disease', 'type': 'Disease', 'start': 117, 'end': 140, 'mesh': 'D017202'}, {'text': 'cardiac failure', 'type': 'Disease', 'start': 160, 'end': 175, 'mesh': 'D006333'}, {'text': 'hypotension', 'type': 'Disease', 'start': 177, 'end': 188, 'mesh': 'D007022'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 193, 'end': 204, 'mesh': 'D001919'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 234, 'end': 243, 'mesh': 'D014700'}, {'text': 'beta-adrenergic blocking drugs', 'type': 'Chemical', 'start': 248, 'end': 278, 'mesh': 'D000319'}, {'text': 'beta-adrenergic blocking drugs', 'type': 'Chemical', 'start': 556, 'end': 586, 'mesh': 'D000319'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 591, 'end': 600, 'mesh': 'D014700'}]"
+638,6115999,Adverse reactions to bendrofluazide and propranolol for the treatment of mild hypertension. Report of Medical Research Council Working Party on Mild to Moderate Hypertension.,"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.","[{'text': 'bendrofluazide', 'type': 'Chemical', 'start': 21, 'end': 35, 'mesh': 'D001539'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 40, 'end': 51, 'mesh': 'D011433'}, {'text': 'hypertension', 'type': 'Disease', 'start': 78, 'end': 90, 'mesh': 'D006973'}, {'text': 'Hypertension', 'type': 'Disease', 'start': 161, 'end': 173, 'mesh': 'D006973'}, {'text': 'hypertension', 'type': 'Disease', 'start': 245, 'end': 257, 'mesh': 'D006973'}, {'text': 'bendrofluazide', 'type': 'Chemical', 'start': 314, 'end': 328, 'mesh': 'D001539'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 330, 'end': 341, 'mesh': 'D011433'}, {'text': 'bendrofluazide', 'type': 'Chemical', 'start': 561, 'end': 575, 'mesh': 'D001539'}, {'text': 'impotence', 'type': 'Disease', 'start': 590, 'end': 599, 'mesh': 'D007172'}, {'text': 'impotence', 'type': 'Disease', 'start': 605, 'end': 614, 'mesh': 'D007172'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 664, 'end': 675, 'mesh': 'D011433'}, {'text': 'impaired glucose tolerance', 'type': 'Disease', 'start': 778, 'end': 804, 'mesh': 'D018149'}, {'text': 'gout', 'type': 'Disease', 'start': 826, 'end': 830, 'mesh': 'D006073'}, {'text': 'bendrofluazide', 'type': 'Chemical', 'start': 855, 'end': 869, 'mesh': 'D001539'}, {'text': ""Raynaud's phenomenon"", 'type': 'Disease', 'start': 885, 'end': 905, 'mesh': 'D011928'}, {'text': 'dyspnoea', 'type': 'Disease', 'start': 910, 'end': 918, 'mesh': 'D004417'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 943, 'end': 954, 'mesh': 'D011433'}, {'text': 'corneal disease', 'type': 'Disease', 'start': 959, 'end': 974, 'mesh': 'D003316'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 1008, 'end': 1019, 'mesh': 'D011433'}, {'text': 'potassium', 'type': 'Chemical', 'start': 1038, 'end': 1047, 'mesh': 'D011188'}, {'text': 'urea', 'type': 'Chemical', 'start': 1064, 'end': 1068, 'mesh': 'D014508'}, {'text': 'uric acid', 'type': 'Chemical', 'start': 1073, 'end': 1082, 'mesh': 'D014527'}, {'text': 'bendrofluazide', 'type': 'Chemical', 'start': 1120, 'end': 1134, 'mesh': 'D001539'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 1143, 'end': 1154, 'mesh': 'D011433'}, {'text': 'potassium', 'type': 'Chemical', 'start': 1168, 'end': 1177, 'mesh': 'D011188'}, {'text': 'uric acid', 'type': 'Chemical', 'start': 1182, 'end': 1191, 'mesh': 'D014527'}, {'text': 'urea', 'type': 'Chemical', 'start': 1227, 'end': 1231, 'mesh': 'D014508'}]"
+639,18086064,Dexmedetomidine and cardiac protection for non-cardiac surgery: a meta-analysis of randomised controlled trials.,"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.","[{'text': 'Dexmedetomidine', 'type': 'Chemical', 'start': 0, 'end': 15, 'mesh': 'D020927'}, {'text': 'dexmedetomidine', 'type': 'Chemical', 'start': 164, 'end': 179, 'mesh': 'D020927'}, {'text': 'dexmedetomidine', 'type': 'Chemical', 'start': 293, 'end': 308, 'mesh': 'D020927'}, {'text': 'Dexmedetomidine', 'type': 'Chemical', 'start': 598, 'end': 613, 'mesh': 'D020927'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 746, 'end': 767, 'mesh': 'D009203'}, {'text': 'myocardial ischaemia', 'type': 'Disease', 'start': 811, 'end': 831, 'mesh': 'D017202'}, {'text': 'hypotension', 'type': 'Disease', 'start': 886, 'end': 897, 'mesh': 'D007022'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 947, 'end': 958, 'mesh': 'D001919'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 1086, 'end': 1097, 'mesh': 'D001919'}, {'text': 'dexmedetomidine', 'type': 'Chemical', 'start': 1151, 'end': 1166, 'mesh': 'D020927'}]"
+640,12739036,Differential diagnosis of high serum creatine kinase levels in systemic lupus erythematosus.,"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.","[{'text': 'creatine', 'type': 'Chemical', 'start': 37, 'end': 45, 'mesh': 'D003401'}, {'text': 'systemic lupus erythematosus', 'type': 'Disease', 'start': 63, 'end': 91, 'mesh': 'D008180'}, {'text': 'chloroquine', 'type': 'Chemical', 'start': 173, 'end': 184, 'mesh': 'D002738'}, {'text': 'myopathy', 'type': 'Disease', 'start': 193, 'end': 201, 'mesh': 'D009135'}, {'text': 'systemic lupus erythematosus', 'type': 'Disease', 'start': 243, 'end': 271, 'mesh': 'D008180'}, {'text': 'SLE', 'type': 'Disease', 'start': 273, 'end': 276, 'mesh': 'D008180'}, {'text': 'renal involvement', 'type': 'Disease', 'start': 283, 'end': 300, 'mesh': 'D007674'}, {'text': 'azathioprine', 'type': 'Chemical', 'start': 341, 'end': 353, 'mesh': 'D001379'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 358, 'end': 374, 'mesh': 'D003520'}, {'text': 'chloroquine', 'type': 'Chemical', 'start': 400, 'end': 411, 'mesh': 'D002738'}, {'text': 'CQ', 'type': 'Chemical', 'start': 413, 'end': 415, 'mesh': 'D002738'}, {'text': 'arthralgia', 'type': 'Disease', 'start': 440, 'end': 450, 'mesh': 'D018771'}, {'text': 'creatine', 'type': 'Chemical', 'start': 489, 'end': 497, 'mesh': 'D003401'}, {'text': 'Myositis', 'type': 'Disease', 'start': 529, 'end': 537, 'mesh': 'D009220'}, {'text': 'steroids', 'type': 'Chemical', 'start': 586, 'end': 594, 'mesh': 'D013256'}, {'text': 'muscular weakness', 'type': 'Disease', 'start': 662, 'end': 679, 'mesh': 'D018908'}, {'text': 'muscular atrophy', 'type': 'Disease', 'start': 684, 'end': 700, 'mesh': 'D009133'}, {'text': 'myositis', 'type': 'Disease', 'start': 841, 'end': 849, 'mesh': 'D009220'}, {'text': 'polymyositis', 'type': 'Disease', 'start': 927, 'end': 939, 'mesh': 'D017285'}, {'text': 'myopathy', 'type': 'Disease', 'start': 949, 'end': 957, 'mesh': 'D009135'}, {'text': 'chloroquine', 'type': 'Chemical', 'start': 974, 'end': 985, 'mesh': 'D002738'}, {'text': 'myopathy', 'type': 'Disease', 'start': 994, 'end': 1002, 'mesh': 'D009135'}, {'text': 'SLE', 'type': 'Disease', 'start': 1059, 'end': 1062, 'mesh': 'D008180'}, {'text': 'affection of the musculoskeletal system', 'type': 'Disease', 'start': 1071, 'end': 1110, 'mesh': 'D009140'}, {'text': 'SLE', 'type': 'Disease', 'start': 1183, 'end': 1186, 'mesh': 'D008180'}]"
+641,12093990,Intravenous ribavirin treatment for severe adenovirus disease in immunocompromised children.,"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.","[{'text': 'ribavirin', 'type': 'Chemical', 'start': 12, 'end': 21, 'mesh': 'D012254'}, {'text': 'adenovirus disease', 'type': 'Disease', 'start': 43, 'end': 61, 'mesh': 'D000257'}, {'text': 'adenovirus disease', 'type': 'Disease', 'start': 220, 'end': 238, 'mesh': 'D000257'}, {'text': 'adenovirus disease', 'type': 'Disease', 'start': 490, 'end': 508, 'mesh': 'D000257'}, {'text': 'adenovirus disease', 'type': 'Disease', 'start': 672, 'end': 690, 'mesh': 'D000257'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 782, 'end': 791, 'mesh': 'D012254'}, {'text': 'cidofovir', 'type': 'Chemical', 'start': 796, 'end': 805, 'mesh': 'C059262'}, {'text': 'Ribavirin', 'type': 'Chemical', 'start': 807, 'end': 816, 'mesh': 'D012254'}, {'text': 'guanosine', 'type': 'Chemical', 'start': 820, 'end': 829, 'mesh': 'D006151'}, {'text': 'Ribavirin', 'type': 'Chemical', 'start': 962, 'end': 971, 'mesh': 'D012254'}, {'text': 'respiratory syncytial virus infection', 'type': 'Disease', 'start': 1021, 'end': 1058, 'mesh': 'D018357'}, {'text': 'hepatitis C', 'type': 'Disease', 'start': 1111, 'end': 1122, 'mesh': 'D006526'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 1136, 'end': 1145, 'mesh': 'D012254'}, {'text': 'infection with hemorrhagic fever viruses', 'type': 'Disease', 'start': 1177, 'end': 1217, 'mesh': 'D006482'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 1265, 'end': 1274, 'mesh': 'D012254'}, {'text': 'anemia', 'type': 'Disease', 'start': 1294, 'end': 1300, 'mesh': 'D000740'}, {'text': 'cidofovir', 'type': 'Chemical', 'start': 1313, 'end': 1322, 'mesh': 'C059262'}, {'text': 'adenovirus infection', 'type': 'Disease', 'start': 1333, 'end': 1353, 'mesh': 'D000257'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1424, 'end': 1438, 'mesh': 'D007674'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 1493, 'end': 1502, 'mesh': 'D012254'}, {'text': 'adenovirus disease', 'type': 'Disease', 'start': 1522, 'end': 1540, 'mesh': 'D000257'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 1713, 'end': 1722, 'mesh': 'D012254'}, {'text': 'adenovirus disease', 'type': 'Disease', 'start': 1745, 'end': 1763, 'mesh': 'D000257'}, {'text': 'cidofovir', 'type': 'Chemical', 'start': 1938, 'end': 1947, 'mesh': 'C059262'}, {'text': 'DiGeorge syndrome', 'type': 'Disease', 'start': 2082, 'end': 2099, 'mesh': 'D004062'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 2179, 'end': 2188, 'mesh': 'D012254'}, {'text': 'adenovirus disease', 'type': 'Disease', 'start': 2499, 'end': 2517, 'mesh': 'D000257'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 2531, 'end': 2540, 'mesh': 'D012254'}, {'text': 'cidofovir', 'type': 'Chemical', 'start': 2576, 'end': 2585, 'mesh': 'C059262'}, {'text': 'progressive renal failure', 'type': 'Disease', 'start': 2617, 'end': 2642, 'mesh': 'D058186'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 2647, 'end': 2658, 'mesh': 'D009503'}, {'text': 'adenovirus disease', 'type': 'Disease', 'start': 2787, 'end': 2805, 'mesh': 'D000257'}, {'text': 'immunodeficiency', 'type': 'Disease', 'start': 2893, 'end': 2909, 'mesh': 'D007153'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 2932, 'end': 2941, 'mesh': 'D012254'}, {'text': 'adenovirus disease', 'type': 'Disease', 'start': 2989, 'end': 3007, 'mesh': 'D000257'}, {'text': 'infection', 'type': 'Disease', 'start': 3117, 'end': 3126, 'mesh': 'D007239'}, {'text': 'adenovirus disease', 'type': 'Disease', 'start': 3224, 'end': 3242, 'mesh': 'D000257'}, {'text': 'adenovirus disease', 'type': 'Disease', 'start': 3372, 'end': 3390, 'mesh': 'D000257'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 3416, 'end': 3425, 'mesh': 'D012254'}, {'text': 'adenovirus infection', 'type': 'Disease', 'start': 3573, 'end': 3593, 'mesh': 'D000257'}, {'text': 'adenovirus disease', 'type': 'Disease', 'start': 3655, 'end': 3673, 'mesh': 'D000257'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 3818, 'end': 3827, 'mesh': 'D012254'}]"
+642,3962737,Hepatotoxicity of amiodarone.,"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.","[{'text': 'Hepatotoxicity', 'type': 'Disease', 'start': 0, 'end': 14, 'mesh': 'D056486'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 18, 'end': 28, 'mesh': 'D000638'}, {'text': 'Amiodarone', 'type': 'Chemical', 'start': 30, 'end': 40, 'mesh': 'D000638'}, {'text': 'tachyarrhythmias', 'type': 'Disease', 'start': 115, 'end': 131, 'mesh': 'D013610'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 144, 'end': 154, 'mesh': 'D000638'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 259, 'end': 269, 'mesh': 'D000638'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 319, 'end': 333, 'mesh': 'D056486'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 337, 'end': 347, 'mesh': 'D000638'}, {'text': 'hepatic injury', 'type': 'Disease', 'start': 404, 'end': 418, 'mesh': 'D056486'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 426, 'end': 436, 'mesh': 'D000638'}, {'text': 'steatosis', 'type': 'Disease', 'start': 458, 'end': 467, 'mesh': 'D005234'}, {'text': 'alcoholic hepatitis', 'type': 'Disease', 'start': 492, 'end': 511, 'mesh': 'D006519'}, {'text': 'cirrhosis of the liver', 'type': 'Disease', 'start': 552, 'end': 574, 'mesh': 'D008103'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 595, 'end': 605, 'mesh': 'D000638'}, {'text': 'cholestatic injury', 'type': 'Disease', 'start': 725, 'end': 743, 'mesh': 'D002779'}, {'text': 'hepatomegaly', 'type': 'Disease', 'start': 747, 'end': 759, 'mesh': 'D006529'}]"
+643,2716967,"Catalepsy induced by combinations of ketamine and morphine: potentiation, antagonism, tolerance and cross-tolerance in the rat.","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 site.","[{'text': 'Catalepsy', 'type': 'Disease', 'start': 0, 'end': 9, 'mesh': 'D002375'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 37, 'end': 45, 'mesh': 'D007649'}, {'text': 'morphine', 'type': 'Chemical', 'start': 50, 'end': 58, 'mesh': 'D009020'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 168, 'end': 176, 'mesh': 'D007649'}, {'text': 'morphine', 'type': 'Chemical', 'start': 181, 'end': 189, 'mesh': 'D009020'}, {'text': 'analgesia', 'type': 'Disease', 'start': 198, 'end': 207, 'mesh': 'D000699'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 212, 'end': 221, 'mesh': 'D002375'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 253, 'end': 261, 'mesh': 'D007649'}, {'text': 'morphine', 'type': 'Chemical', 'start': 290, 'end': 298, 'mesh': 'D009020'}, {'text': 'morphine', 'type': 'Chemical', 'start': 326, 'end': 334, 'mesh': 'D009020'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 369, 'end': 377, 'mesh': 'D007649'}, {'text': 'cataleptic', 'type': 'Disease', 'start': 403, 'end': 413, 'mesh': 'D002375'}, {'text': 'morphine', 'type': 'Chemical', 'start': 469, 'end': 477, 'mesh': 'D009020'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 599, 'end': 607, 'mesh': 'D007649'}, {'text': 'morphine', 'type': 'Chemical', 'start': 612, 'end': 620, 'mesh': 'D009020'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 712, 'end': 720, 'mesh': 'D007649'}, {'text': 'morphine', 'type': 'Chemical', 'start': 725, 'end': 733, 'mesh': 'D009020'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 762, 'end': 770, 'mesh': 'D007649'}, {'text': 'morphine', 'type': 'Chemical', 'start': 815, 'end': 823, 'mesh': 'D009020'}, {'text': 'rigidity', 'type': 'Disease', 'start': 865, 'end': 873, 'mesh': 'D009127'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 939, 'end': 947, 'mesh': 'D007649'}, {'text': 'morphine', 'type': 'Chemical', 'start': 951, 'end': 959, 'mesh': 'D009020'}, {'text': 'Naloxone', 'type': 'Chemical', 'start': 981, 'end': 989, 'mesh': 'D009270'}, {'text': 'cataleptic', 'type': 'Disease', 'start': 1012, 'end': 1022, 'mesh': 'D002375'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 1149, 'end': 1157, 'mesh': 'D007649'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1162, 'end': 1170, 'mesh': 'D009020'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 1203, 'end': 1211, 'mesh': 'D007649'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1294, 'end': 1302, 'mesh': 'D009020'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1348, 'end': 1356, 'mesh': 'D009020'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 1422, 'end': 1430, 'mesh': 'D007649'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 1530, 'end': 1539, 'mesh': 'D002375'}, {'text': 'rigidity', 'type': 'Disease', 'start': 1565, 'end': 1573, 'mesh': 'D009127'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 1649, 'end': 1657, 'mesh': 'D009270'}]"
+644,19642243,Acute renal failure in patients with AIDS on tenofovir while receiving prolonged vancomycin course for osteomyelitis.,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.,"[{'text': 'Acute renal failure', 'type': 'Disease', 'start': 0, 'end': 19, 'mesh': 'D058186'}, {'text': 'AIDS', 'type': 'Disease', 'start': 37, 'end': 41, 'mesh': 'D000163'}, {'text': 'tenofovir', 'type': 'Chemical', 'start': 45, 'end': 54, 'mesh': 'C096918'}, {'text': 'vancomycin', 'type': 'Chemical', 'start': 81, 'end': 91, 'mesh': 'D014640'}, {'text': 'osteomyelitis', 'type': 'Disease', 'start': 103, 'end': 116, 'mesh': 'D010019'}, {'text': 'Renal failure', 'type': 'Disease', 'start': 118, 'end': 131, 'mesh': 'D051437'}, {'text': 'vancomycin', 'type': 'Chemical', 'start': 170, 'end': 180, 'mesh': 'D014640'}, {'text': 'tenofovir disoproxil fumarate', 'type': 'Chemical', 'start': 222, 'end': 251, 'mesh': 'C418563'}, {'text': 'Tenofovir', 'type': 'Chemical', 'start': 290, 'end': 299, 'mesh': 'C096918'}, {'text': 'Fanconi syndrome', 'type': 'Disease', 'start': 342, 'end': 358, 'mesh': 'D005198'}, {'text': 'renal insufficiency', 'type': 'Disease', 'start': 363, 'end': 382, 'mesh': 'D051437'}, {'text': 'Vancomycin', 'type': 'Chemical', 'start': 436, 'end': 446, 'mesh': 'D014640'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 447, 'end': 461, 'mesh': 'D007674'}, {'text': 'nephrotoxic', 'type': 'Disease', 'start': 520, 'end': 531, 'mesh': 'D007674'}, {'text': 'tenofovir', 'type': 'Chemical', 'start': 571, 'end': 580, 'mesh': 'C096918'}, {'text': 'renal failure', 'type': 'Disease', 'start': 603, 'end': 616, 'mesh': 'D051437'}, {'text': 'vancomycin', 'type': 'Chemical', 'start': 652, 'end': 662, 'mesh': 'D014640'}]"
+645,17682013,Delayed leukoencephalopathy with stroke-like presentation in chemotherapy recipients.,"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.","[{'text': 'leukoencephalopathy', 'type': 'Disease', 'start': 8, 'end': 27, 'mesh': 'D056784'}, {'text': 'stroke', 'type': 'Disease', 'start': 33, 'end': 39, 'mesh': 'D020521'}, {'text': 'leukoencephalopathy', 'type': 'Disease', 'start': 110, 'end': 129, 'mesh': 'D056784'}, {'text': 'cerebrovascular accident', 'type': 'Disease', 'start': 140, 'end': 164, 'mesh': 'D002544'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 262, 'end': 274, 'mesh': 'D008727'}, {'text': 'leukaemia', 'type': 'Disease', 'start': 289, 'end': 298, 'mesh': 'D007938'}, {'text': 'stroke', 'type': 'Disease', 'start': 555, 'end': 561, 'mesh': 'D020521'}, {'text': 'cerebrovascular accidents', 'type': 'Disease', 'start': 707, 'end': 732, 'mesh': 'D002544'}, {'text': 'leukoencephalopathy', 'type': 'Disease', 'start': 791, 'end': 810, 'mesh': 'D056784'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 836, 'end': 848, 'mesh': 'D008727'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 874, 'end': 888, 'mesh': 'D005472'}, {'text': 'carmofur', 'type': 'Chemical', 'start': 908, 'end': 916, 'mesh': 'C017367'}, {'text': 'capecitabine', 'type': 'Chemical', 'start': 922, 'end': 934, 'mesh': 'C110904'}, {'text': 'lesions within the subcortical white matter', 'type': 'Disease', 'start': 1023, 'end': 1066, 'mesh': 'D056784'}, {'text': 'white matter abnormalities', 'type': 'Disease', 'start': 1510, 'end': 1536, 'mesh': 'D056784'}, {'text': 'leukoencephalopathy', 'type': 'Disease', 'start': 1596, 'end': 1615, 'mesh': 'D056784'}, {'text': 'cytotoxic oedema within cerebral white matter', 'type': 'Disease', 'start': 1737, 'end': 1782, 'mesh': 'D001929'}]"
+646,16725121,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.,"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.","[{'text': 'norepinephrine', 'type': 'Chemical', 'start': 19, 'end': 33, 'mesh': 'D009638'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 92, 'end': 103, 'mesh': 'D003891'}, {'text': 'convulsions', 'type': 'Disease', 'start': 174, 'end': 185, 'mesh': 'D012640'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 268, 'end': 282, 'mesh': 'D009638'}, {'text': 'seizures', 'type': 'Disease', 'start': 371, 'end': 379, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 390, 'end': 397, 'mesh': 'D003042'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 466, 'end': 477, 'mesh': 'D003891'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 531, 'end': 545, 'mesh': 'D009638'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 648, 'end': 657, 'mesh': 'D008012'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 659, 'end': 670, 'mesh': 'D002045'}, {'text': 'tricaine', 'type': 'Chemical', 'start': 674, 'end': 682, 'mesh': 'C003636'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 688, 'end': 699, 'mesh': 'D003891'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 741, 'end': 748, 'mesh': 'D003042'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 765, 'end': 779, 'mesh': 'D009638'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 833, 'end': 844, 'mesh': 'D003891'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 886, 'end': 895, 'mesh': 'D008012'}, {'text': 'convulsions', 'type': 'Disease', 'start': 904, 'end': 915, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 938, 'end': 945, 'mesh': 'D003042'}, {'text': 'convulsions', 'type': 'Disease', 'start': 954, 'end': 965, 'mesh': 'D012640'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 988, 'end': 997, 'mesh': 'D008012'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 1003, 'end': 1014, 'mesh': 'D003891'}, {'text': 'convulsive', 'type': 'Disease', 'start': 1039, 'end': 1049, 'mesh': 'D012640'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 1062, 'end': 1071, 'mesh': 'D008012'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1076, 'end': 1083, 'mesh': 'D003042'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 1122, 'end': 1133, 'mesh': 'D003891'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 1234, 'end': 1245, 'mesh': 'D003891'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 1265, 'end': 1276, 'mesh': 'D003891'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 1302, 'end': 1311, 'mesh': 'D008012'}, {'text': 'convulsions', 'type': 'Disease', 'start': 1312, 'end': 1323, 'mesh': 'D012640'}, {'text': 'Na', 'type': 'Chemical', 'start': 1339, 'end': 1341, 'mesh': 'D012964'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 1388, 'end': 1399, 'mesh': 'D003891'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1468, 'end': 1475, 'mesh': 'D003042'}, {'text': 'Desipramine', 'type': 'Chemical', 'start': 1527, 'end': 1538, 'mesh': 'D003891'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 1564, 'end': 1573, 'mesh': 'D008012'}, {'text': 'seizures', 'type': 'Disease', 'start': 1574, 'end': 1582, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1669, 'end': 1676, 'mesh': 'D003042'}]"
+647,16629641,Definition and management of anemia in patients infected with hepatitis C virus.,"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.","[{'text': 'anemia', 'type': 'Disease', 'start': 29, 'end': 35, 'mesh': 'D000740'}, {'text': 'infected with hepatitis C virus', 'type': 'Disease', 'start': 48, 'end': 79, 'mesh': 'D006526'}, {'text': 'Chronic infection with hepatitis C virus', 'type': 'Disease', 'start': 81, 'end': 121, 'mesh': 'D019698'}, {'text': 'cirrhosis', 'type': 'Disease', 'start': 144, 'end': 153, 'mesh': 'D005355'}, {'text': 'hepatocellular carcinoma', 'type': 'Disease', 'start': 155, 'end': 179, 'mesh': 'D006528'}, {'text': 'end-stage liver disease', 'type': 'Disease', 'start': 185, 'end': 208, 'mesh': 'D058625'}, {'text': 'HCV infection', 'type': 'Disease', 'start': 241, 'end': 254, 'mesh': 'D006526'}, {'text': 'interferon', 'type': 'Chemical', 'start': 293, 'end': 303, 'mesh': 'D007372'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 308, 'end': 317, 'mesh': 'D012254'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 475, 'end': 491, 'mesh': 'D000743'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 550, 'end': 559, 'mesh': 'D012254'}, {'text': 'hemolysis', 'type': 'Disease', 'start': 568, 'end': 577, 'mesh': 'D006461'}, {'text': 'anemia', 'type': 'Disease', 'start': 588, 'end': 594, 'mesh': 'D000740'}, {'text': 'HCV infection', 'type': 'Disease', 'start': 631, 'end': 644, 'mesh': 'D006526'}, {'text': 'anemia', 'type': 'Disease', 'start': 728, 'end': 734, 'mesh': 'D000740'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 866, 'end': 875, 'mesh': 'D012254'}, {'text': 'anemia', 'type': 'Disease', 'start': 887, 'end': 893, 'mesh': 'D000740'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 1079, 'end': 1088, 'mesh': 'D012254'}, {'text': 'anemia', 'type': 'Disease', 'start': 1100, 'end': 1106, 'mesh': 'D000740'}, {'text': 'Viramidine', 'type': 'Chemical', 'start': 1146, 'end': 1156, 'mesh': 'C026956'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 1187, 'end': 1196, 'mesh': 'D012254'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 1254, 'end': 1263, 'mesh': 'D012254'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 1293, 'end': 1309, 'mesh': 'D000743'}, {'text': 'chronic hepatitis C', 'type': 'Disease', 'start': 1327, 'end': 1346, 'mesh': 'D019698'}]"
+648,16006300,Calcium carbonate toxicity: the updated milk-alkali syndrome; report of 3 cases and review of the literature.,"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.","[{'text': 'Calcium carbonate', 'type': 'Chemical', 'start': 0, 'end': 17, 'mesh': 'D002119'}, {'text': 'toxicity', 'type': 'Disease', 'start': 18, 'end': 26, 'mesh': 'D064420'}, {'text': 'milk-alkali syndrome', 'type': 'Disease', 'start': 40, 'end': 60, 'mesh': 'D006934'}, {'text': 'calcium carbonate', 'type': 'Chemical', 'start': 149, 'end': 166, 'mesh': 'D002119'}, {'text': 'hypercalcemia', 'type': 'Disease', 'start': 175, 'end': 188, 'mesh': 'D006934'}, {'text': 'milk-alkali syndrome', 'type': 'Disease', 'start': 244, 'end': 264, 'mesh': 'D006934'}, {'text': 'hypercalcemia', 'type': 'Disease', 'start': 358, 'end': 371, 'mesh': 'D006934'}, {'text': 'calcium', 'type': 'Chemical', 'start': 389, 'end': 396, 'mesh': 'D002118'}, {'text': 'milk-alkali syndrome', 'type': 'Disease', 'start': 453, 'end': 473, 'mesh': 'D006934'}, {'text': 'acute renal insufficiency', 'type': 'Disease', 'start': 503, 'end': 528, 'mesh': 'D058186'}, {'text': 'metabolic alkalosis', 'type': 'Disease', 'start': 539, 'end': 558, 'mesh': 'D000471'}, {'text': '1,25-dihydroxyvitamin D', 'type': 'Chemical', 'start': 620, 'end': 643, 'mesh': 'C097949'}, {'text': 'furosemide', 'type': 'Chemical', 'start': 753, 'end': 763, 'mesh': 'D005665'}, {'text': 'calcium', 'type': 'Chemical', 'start': 802, 'end': 809, 'mesh': 'D002118'}, {'text': 'pamidronate', 'type': 'Chemical', 'start': 834, 'end': 845, 'mesh': 'C019248'}, {'text': 'hypocalcemia', 'type': 'Disease', 'start': 910, 'end': 922, 'mesh': 'D006996'}, {'text': 'calcium', 'type': 'Chemical', 'start': 990, 'end': 997, 'mesh': 'D002118'}, {'text': 'calcium carbonate', 'type': 'Chemical', 'start': 1047, 'end': 1064, 'mesh': 'D002119'}, {'text': 'milk-alkali syndrome', 'type': 'Disease', 'start': 1187, 'end': 1207, 'mesh': 'D006934'}, {'text': 'Milk-alkali syndrome', 'type': 'Disease', 'start': 1287, 'end': 1307, 'mesh': 'D006934'}, {'text': 'hypercalcemia', 'type': 'Disease', 'start': 1345, 'end': 1358, 'mesh': 'D006934'}, {'text': 'calcium carbonate', 'type': 'Chemical', 'start': 1419, 'end': 1436, 'mesh': 'D002119'}, {'text': 'furosemide', 'type': 'Chemical', 'start': 1487, 'end': 1497, 'mesh': 'D005665'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1526, 'end': 1533, 'mesh': 'D002118'}, {'text': 'vitamin D', 'type': 'Chemical', 'start': 1538, 'end': 1547, 'mesh': 'D014807'}, {'text': 'Pamidronate', 'type': 'Chemical', 'start': 1568, 'end': 1579, 'mesh': 'C019248'}, {'text': 'hypocalcemia', 'type': 'Disease', 'start': 1631, 'end': 1643, 'mesh': 'D006996'}, {'text': 'hypercalcemia', 'type': 'Disease', 'start': 1679, 'end': 1692, 'mesh': 'D006934'}]"
+649,11705128,Management strategies for ribavirin-induced hemolytic anemia in the treatment of hepatitis C: clinical and economic implications.,"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.","[{'text': 'ribavirin', 'type': 'Chemical', 'start': 26, 'end': 35, 'mesh': 'D012254'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 44, 'end': 60, 'mesh': 'D000743'}, {'text': 'hepatitis C', 'type': 'Disease', 'start': 81, 'end': 92, 'mesh': 'D006526'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 281, 'end': 290, 'mesh': 'D012254'}, {'text': 'interferon-alpha', 'type': 'Chemical', 'start': 305, 'end': 321, 'mesh': 'D016898'}, {'text': 'chronic hepatitis C', 'type': 'Disease', 'start': 354, 'end': 373, 'mesh': 'D019698'}, {'text': 'CHC', 'type': 'Disease', 'start': 375, 'end': 378, 'mesh': 'D019698'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 459, 'end': 468, 'mesh': 'D012254'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 477, 'end': 493, 'mesh': 'D000743'}, {'text': 'RIHA', 'type': 'Disease', 'start': 495, 'end': 499, 'mesh': 'D000743'}, {'text': 'RIHA', 'type': 'Disease', 'start': 593, 'end': 597, 'mesh': 'D000743'}, {'text': 'CHC', 'type': 'Disease', 'start': 618, 'end': 621, 'mesh': 'D019698'}, {'text': 'RIHA', 'type': 'Disease', 'start': 766, 'end': 770, 'mesh': 'D000743'}, {'text': 'RIHA', 'type': 'Disease', 'start': 844, 'end': 848, 'mesh': 'D000743'}, {'text': 'RIHA', 'type': 'Disease', 'start': 913, 'end': 917, 'mesh': 'D000743'}, {'text': 'RIHA', 'type': 'Disease', 'start': 1096, 'end': 1100, 'mesh': 'D000743'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 1140, 'end': 1149, 'mesh': 'D012254'}, {'text': 'RIHA', 'type': 'Disease', 'start': 1222, 'end': 1226, 'mesh': 'D000743'}, {'text': 'RIHA', 'type': 'Disease', 'start': 1535, 'end': 1539, 'mesh': 'D000743'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 1629, 'end': 1638, 'mesh': 'D012254'}, {'text': 'RIHA', 'type': 'Disease', 'start': 1660, 'end': 1664, 'mesh': 'D000743'}, {'text': 'RIHA', 'type': 'Disease', 'start': 1777, 'end': 1781, 'mesh': 'D000743'}]"
+650,6540303,Effects of amine pretreatment on ketamine catatonia in pinealectomized or hypophysectomized animals.,"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.","[{'text': 'amine', 'type': 'Chemical', 'start': 11, 'end': 16, 'mesh': 'D000588'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 33, 'end': 41, 'mesh': 'D007649'}, {'text': 'catatonia', 'type': 'Disease', 'start': 42, 'end': 51, 'mesh': 'D002389'}, {'text': 'catecholamines', 'type': 'Chemical', 'start': 158, 'end': 172, 'mesh': 'D002395'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 198, 'end': 206, 'mesh': 'D007649'}, {'text': 'catatonia', 'type': 'Disease', 'start': 215, 'end': 224, 'mesh': 'D002389'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 340, 'end': 348, 'mesh': 'D004298'}, {'text': 'catatonia', 'type': 'Disease', 'start': 375, 'end': 384, 'mesh': 'D002389'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 397, 'end': 405, 'mesh': 'D007649'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 429, 'end': 443, 'mesh': 'D009638'}, {'text': 'Serotonin', 'type': 'Chemical', 'start': 501, 'end': 510, 'mesh': 'D012701'}, {'text': 'N-acetyl serotonin', 'type': 'Chemical', 'start': 515, 'end': 533, 'mesh': 'C006389'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 550, 'end': 558, 'mesh': 'D007649'}, {'text': 'melatonin', 'type': 'Chemical', 'start': 622, 'end': 631, 'mesh': 'D008550'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 648, 'end': 656, 'mesh': 'D007649'}, {'text': 'Ketamine', 'type': 'Chemical', 'start': 707, 'end': 715, 'mesh': 'D007649'}, {'text': 'melatonin', 'type': 'Chemical', 'start': 839, 'end': 848, 'mesh': 'D008550'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 869, 'end': 877, 'mesh': 'D007649'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 890, 'end': 898, 'mesh': 'D004298'}, {'text': 'amines', 'type': 'Chemical', 'start': 997, 'end': 1003, 'mesh': 'D000588'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 1204, 'end': 1212, 'mesh': 'D007649'}, {'text': 'melatonin', 'type': 'Chemical', 'start': 1228, 'end': 1237, 'mesh': 'D008550'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1252, 'end': 1260, 'mesh': 'D004298'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 1332, 'end': 1340, 'mesh': 'D007649'}, {'text': 'catatonia', 'type': 'Disease', 'start': 1341, 'end': 1350, 'mesh': 'D002389'}]"
+651,3057041,"Multicenter, double-blind, multiple-dose, parallel-groups efficacy and safety trial of azelastine, chlorpheniramine, and placebo in the treatment of spring allergic rhinitis.","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.","[{'text': 'azelastine', 'type': 'Chemical', 'start': 87, 'end': 97, 'mesh': 'C020976'}, {'text': 'chlorpheniramine', 'type': 'Chemical', 'start': 99, 'end': 115, 'mesh': 'D002744'}, {'text': 'spring allergic rhinitis', 'type': 'Disease', 'start': 149, 'end': 173, 'mesh': 'D006255'}, {'text': 'Azelastine', 'type': 'Chemical', 'start': 175, 'end': 185, 'mesh': 'C020976'}, {'text': 'chlorpheniramine maleate', 'type': 'Chemical', 'start': 238, 'end': 262, 'mesh': 'D002744'}, {'text': 'spring allergic rhinitis', 'type': 'Disease', 'start': 319, 'end': 343, 'mesh': 'D006255'}, {'text': 'spring allergic rhinitis', 'type': 'Disease', 'start': 547, 'end': 571, 'mesh': 'D006255'}, {'text': 'azelastine', 'type': 'Chemical', 'start': 675, 'end': 685, 'mesh': 'C020976'}, {'text': 'chlorpheniramine', 'type': 'Chemical', 'start': 799, 'end': 815, 'mesh': 'D002744'}, {'text': 'azelastine', 'type': 'Chemical', 'start': 1501, 'end': 1511, 'mesh': 'C020976'}, {'text': 'azelastine', 'type': 'Chemical', 'start': 1631, 'end': 1641, 'mesh': 'C020976'}, {'text': 'chlorpheniramine', 'type': 'Chemical', 'start': 1771, 'end': 1787, 'mesh': 'D002744'}, {'text': 'Drowsiness', 'type': 'Disease', 'start': 2010, 'end': 2020, 'mesh': 'D006970'}, {'text': 'altered taste perception', 'type': 'Disease', 'start': 2025, 'end': 2049, 'mesh': 'D013651'}, {'text': 'azelastine', 'type': 'Chemical', 'start': 2114, 'end': 2124, 'mesh': 'C020976'}, {'text': 'Azelastine', 'type': 'Chemical', 'start': 2132, 'end': 2142, 'mesh': 'C020976'}, {'text': 'seasonal allergic rhinitis', 'type': 'Disease', 'start': 2192, 'end': 2218, 'mesh': 'D006255'}]"
+652,625456,Obsolete but dangerous antacid preparations.,"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.","[{'text': 'hypercalcaemia', 'type': 'Disease', 'start': 63, 'end': 77, 'mesh': 'D006934'}, {'text': 'nephrolithiasis', 'type': 'Disease', 'start': 99, 'end': 114, 'mesh': 'D053040'}, {'text': 'calcium carbon-ate', 'type': 'Chemical', 'start': 184, 'end': 202, 'mesh': 'D002119'}, {'text': 'sodium bicarbonate', 'type': 'Chemical', 'start': 203, 'end': 221, 'mesh': 'D017693'}]"
+653,7910951,Prolonged paralysis due to nondepolarizing neuromuscular blocking agents and corticosteroids.,"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.","[{'text': 'paralysis', 'type': 'Disease', 'start': 10, 'end': 19, 'mesh': 'D010243'}, {'text': 'nondepolarizing neuromuscular blocking agents', 'type': 'Chemical', 'start': 27, 'end': 72, 'mesh': 'D003473'}, {'text': 'corticosteroids', 'type': 'Chemical', 'start': 77, 'end': 92, 'mesh': 'D000305'}, {'text': 'nondepolarizing neuromuscular blocking agents', 'type': 'Chemical', 'start': 115, 'end': 160, 'mesh': 'D003473'}, {'text': 'ND-NMBA', 'type': 'Chemical', 'start': 162, 'end': 169, 'mesh': 'D003473'}, {'text': 'muscle weakness', 'type': 'Disease', 'start': 224, 'end': 239, 'mesh': 'D018908'}, {'text': 'respiratory insufficiency', 'type': 'Disease', 'start': 371, 'end': 396, 'mesh': 'D012131'}, {'text': 'weakness', 'type': 'Disease', 'start': 421, 'end': 429, 'mesh': 'D018908'}, {'text': 'ND-NMBAs', 'type': 'Chemical', 'start': 463, 'end': 471, 'mesh': 'D003473'}, {'text': 'corticosteroids', 'type': 'Chemical', 'start': 512, 'end': 527, 'mesh': 'D000305'}, {'text': 'acidosis', 'type': 'Disease', 'start': 618, 'end': 626, 'mesh': 'D000138'}, {'text': 'vecuronium', 'type': 'Chemical', 'start': 841, 'end': 851, 'mesh': 'D014673'}, {'text': 'loss of thick, myosin filaments', 'type': 'Disease', 'start': 979, 'end': 1010, 'mesh': 'D009135'}, {'text': 'weakness', 'type': 'Disease', 'start': 1016, 'end': 1024, 'mesh': 'D018908'}, {'text': 'pathology at both the neuromuscular junction', 'type': 'Disease', 'start': 1053, 'end': 1097, 'mesh': 'D009468'}, {'text': 'ND-NMBA', 'type': 'Chemical', 'start': 1118, 'end': 1125, 'mesh': 'D003473'}, {'text': 'corticosteroids', 'type': 'Chemical', 'start': 1158, 'end': 1173, 'mesh': 'D000305'}, {'text': 'Hepatic dysfunction', 'type': 'Disease', 'start': 1176, 'end': 1195, 'mesh': 'D008107'}, {'text': 'acidosis', 'type': 'Disease', 'start': 1200, 'end': 1208, 'mesh': 'D000138'}]"
+654,7752389,"Prostaglandin E2-induced bladder hyperactivity in normal, conscious rats: involvement of tachykinins?","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.","[{'text': 'Prostaglandin E2', 'type': 'Chemical', 'start': 0, 'end': 16, 'mesh': 'D015232'}, {'text': 'bladder hyperactivity', 'type': 'Disease', 'start': 25, 'end': 46, 'mesh': 'D053201'}, {'text': 'tachykinins', 'type': 'Chemical', 'start': 89, 'end': 100, 'mesh': 'D015320'}, {'text': 'prostaglandin (PG) E2', 'type': 'Chemical', 'start': 191, 'end': 212, 'mesh': 'D015232'}, {'text': 'RP 67,580', 'type': 'Chemical', 'start': 352, 'end': 361, 'mesh': 'C071693'}, {'text': 'SR 48,968', 'type': 'Chemical', 'start': 404, 'end': 413, 'mesh': 'C073839'}, {'text': 'PGE2', 'type': 'Chemical', 'start': 540, 'end': 544, 'mesh': 'D015232'}, {'text': 'PG', 'type': 'Chemical', 'start': 654, 'end': 656, 'mesh': 'D011453'}, {'text': 'PGE2', 'type': 'Chemical', 'start': 749, 'end': 753, 'mesh': 'D015232'}, {'text': 'RP 67,580', 'type': 'Chemical', 'start': 793, 'end': 802, 'mesh': 'C071693'}, {'text': 'SR 48,968', 'type': 'Chemical', 'start': 806, 'end': 815, 'mesh': 'C073839'}, {'text': 'PGE2', 'type': 'Chemical', 'start': 900, 'end': 904, 'mesh': 'D015232'}, {'text': 'PG', 'type': 'Chemical', 'start': 971, 'end': 973, 'mesh': 'D011453'}, {'text': 'PGE2', 'type': 'Chemical', 'start': 1053, 'end': 1057, 'mesh': 'D015232'}, {'text': 'PGE2', 'type': 'Chemical', 'start': 1229, 'end': 1233, 'mesh': 'D015232'}, {'text': 'tachykinins', 'type': 'Chemical', 'start': 1273, 'end': 1284, 'mesh': 'D015320'}, {'text': 'tachykinins', 'type': 'Chemical', 'start': 1347, 'end': 1358, 'mesh': 'D015320'}, {'text': 'Prostanoids', 'type': 'Chemical', 'start': 1437, 'end': 1448, 'mesh': 'D011453'}, {'text': 'tachykinins', 'type': 'Chemical', 'start': 1469, 'end': 1480, 'mesh': 'D015320'}, {'text': 'bladder hyperactivity', 'type': 'Disease', 'start': 1510, 'end': 1531, 'mesh': 'D053201'}]"
+655,6942642,"Thiazide diuretics, hypokalemia and cardiac arrhythmias.","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.","[{'text': 'Thiazide', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D049971'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 20, 'end': 31, 'mesh': 'D007008'}, {'text': 'cardiac arrhythmias', 'type': 'Disease', 'start': 36, 'end': 55, 'mesh': 'D001145'}, {'text': 'Thiazide', 'type': 'Chemical', 'start': 57, 'end': 65, 'mesh': 'D049971'}, {'text': 'Hypokalemia', 'type': 'Disease', 'start': 155, 'end': 166, 'mesh': 'D007008'}, {'text': 'thiazide', 'type': 'Chemical', 'start': 226, 'end': 234, 'mesh': 'D049971'}, {'text': 'diastolic hypertension', 'type': 'Disease', 'start': 313, 'end': 335, 'mesh': 'C563897'}, {'text': 'hydrochlorothiazide', 'type': 'Chemical', 'start': 341, 'end': 360, 'mesh': 'D006852'}, {'text': 'HCTC', 'type': 'Chemical', 'start': 362, 'end': 366, 'mesh': 'D006852'}, {'text': 'K', 'type': 'Chemical', 'start': 557, 'end': 558, 'mesh': 'D011188'}, {'text': 'HCTZ', 'type': 'Chemical', 'start': 637, 'end': 641, 'mesh': 'D006852'}, {'text': 'K', 'type': 'Chemical', 'start': 761, 'end': 762, 'mesh': 'D011188'}, {'text': 'HCTZ', 'type': 'Chemical', 'start': 902, 'end': 906, 'mesh': 'D006852'}, {'text': 'HCTZ', 'type': 'Chemical', 'start': 1188, 'end': 1192, 'mesh': 'D006852'}, {'text': 'K', 'type': 'Chemical', 'start': 1347, 'end': 1348, 'mesh': 'D011188'}, {'text': 'thiazide', 'type': 'Chemical', 'start': 1416, 'end': 1424, 'mesh': 'D049971'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 1441, 'end': 1452, 'mesh': 'D007008'}, {'text': 'potassium', 'type': 'Chemical', 'start': 1475, 'end': 1484, 'mesh': 'D011188'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 1504, 'end': 1515, 'mesh': 'D007008'}]"
+656,3732088,"Diuretics, potassium and arrhythmias in hypertensive coronary disease.","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.","[{'text': 'potassium', 'type': 'Chemical', 'start': 11, 'end': 20, 'mesh': 'D011188'}, {'text': 'arrhythmias', 'type': 'Disease', 'start': 25, 'end': 36, 'mesh': 'D001145'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 40, 'end': 52, 'mesh': 'D006973'}, {'text': 'coronary disease', 'type': 'Disease', 'start': 53, 'end': 69, 'mesh': 'D003327'}, {'text': 'potassium', 'type': 'Chemical', 'start': 122, 'end': 131, 'mesh': 'D011188'}, {'text': 'cardiac arrhythmias', 'type': 'Disease', 'start': 163, 'end': 182, 'mesh': 'D001145'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 215, 'end': 238, 'mesh': 'D003324'}, {'text': 'hypertension', 'type': 'Disease', 'start': 358, 'end': 370, 'mesh': 'D006973'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 381, 'end': 404, 'mesh': 'D003324'}, {'text': 'potassium', 'type': 'Chemical', 'start': 439, 'end': 448, 'mesh': 'D011188'}, {'text': 'amiloride', 'type': 'Chemical', 'start': 470, 'end': 479, 'mesh': 'D000584'}, {'text': 'potassium', 'type': 'Chemical', 'start': 507, 'end': 516, 'mesh': 'D011188'}, {'text': 'chlorthalidone', 'type': 'Chemical', 'start': 534, 'end': 548, 'mesh': 'D002752'}, {'text': 'potassium', 'type': 'Chemical', 'start': 580, 'end': 589, 'mesh': 'D011188'}, {'text': 'chlorthalidone', 'type': 'Chemical', 'start': 647, 'end': 661, 'mesh': 'D002752'}, {'text': 'amiloride', 'type': 'Chemical', 'start': 680, 'end': 689, 'mesh': 'D000584'}, {'text': 'noradrenaline', 'type': 'Chemical', 'start': 776, 'end': 789, 'mesh': 'D009638'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 791, 'end': 805, 'mesh': 'D009638'}, {'text': 'amiloride', 'type': 'Chemical', 'start': 866, 'end': 875, 'mesh': 'D000584'}, {'text': 'chlorthalidone', 'type': 'Chemical', 'start': 891, 'end': 905, 'mesh': 'D002752'}, {'text': 'ventricular ectopic beats', 'type': 'Disease', 'start': 958, 'end': 983, 'mesh': 'D018879'}, {'text': 'potassium', 'type': 'Chemical', 'start': 1277, 'end': 1286, 'mesh': 'D011188'}, {'text': 'ischaemic heart disease', 'type': 'Disease', 'start': 1376, 'end': 1399, 'mesh': 'D017202'}, {'text': 'potassium', 'type': 'Chemical', 'start': 1428, 'end': 1437, 'mesh': 'D011188'}]"
+657,2893236,GABA involvement in naloxone induced reversal of respiratory paralysis produced by thiopental.,"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.","[{'text': 'GABA', 'type': 'Chemical', 'start': 0, 'end': 4, 'mesh': 'D005680'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 20, 'end': 28, 'mesh': 'D009270'}, {'text': 'respiratory paralysis', 'type': 'Disease', 'start': 49, 'end': 70, 'mesh': 'D012133'}, {'text': 'thiopental', 'type': 'Chemical', 'start': 83, 'end': 93, 'mesh': 'D013874'}, {'text': 'respiratory paralysis', 'type': 'Disease', 'start': 132, 'end': 153, 'mesh': 'D012133'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 226, 'end': 234, 'mesh': 'D009270'}, {'text': 'respiratory paralysis', 'type': 'Disease', 'start': 244, 'end': 265, 'mesh': 'D012133'}, {'text': 'thiopental', 'type': 'Chemical', 'start': 277, 'end': 287, 'mesh': 'D013874'}, {'text': 'thiopental', 'type': 'Chemical', 'start': 312, 'end': 322, 'mesh': 'D013874'}, {'text': 'GABA', 'type': 'Chemical', 'start': 388, 'end': 392, 'mesh': 'D005680'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 404, 'end': 413, 'mesh': 'D018698'}, {'text': 'aspartate', 'type': 'Chemical', 'start': 436, 'end': 445, 'mesh': 'D001224'}, {'text': 'glycine', 'type': 'Chemical', 'start': 449, 'end': 456, 'mesh': 'D005998'}, {'text': 'thiosemicarbazide', 'type': 'Chemical', 'start': 541, 'end': 558, 'mesh': 'C005151'}, {'text': 'thiopental', 'type': 'Chemical', 'start': 654, 'end': 664, 'mesh': 'D013874'}, {'text': 'thiopental', 'type': 'Chemical', 'start': 681, 'end': 691, 'mesh': 'D013874'}, {'text': 'respiratory arrest', 'type': 'Disease', 'start': 701, 'end': 719, 'mesh': 'D012131'}, {'text': 'GABA', 'type': 'Chemical', 'start': 745, 'end': 749, 'mesh': 'D005680'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 766, 'end': 775, 'mesh': 'D018698'}, {'text': 'amino acids', 'type': 'Chemical', 'start': 836, 'end': 847, 'mesh': 'D000596'}, {'text': 'Naloxone', 'type': 'Chemical', 'start': 886, 'end': 894, 'mesh': 'D009270'}, {'text': 'respiratory paralysis', 'type': 'Disease', 'start': 922, 'end': 943, 'mesh': 'D012133'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 945, 'end': 954, 'mesh': 'D018698'}, {'text': 'GABA', 'type': 'Chemical', 'start': 959, 'end': 963, 'mesh': 'D005680'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 1075, 'end': 1083, 'mesh': 'D009270'}, {'text': 'respiratory paralysis', 'type': 'Disease', 'start': 1093, 'end': 1114, 'mesh': 'D012133'}, {'text': 'thiopental', 'type': 'Chemical', 'start': 1127, 'end': 1137, 'mesh': 'D013874'}, {'text': 'GABA', 'type': 'Chemical', 'start': 1151, 'end': 1155, 'mesh': 'D005680'}]"
+658,2533791,National project on the prevention of mother-to-infant infection by hepatitis B virus in Japan.,"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.","[{'text': 'infection by hepatitis B virus', 'type': 'Disease', 'start': 55, 'end': 85, 'mesh': 'D006509'}, {'text': 'infection by hepatitis B virus', 'type': 'Disease', 'start': 163, 'end': 193, 'mesh': 'D006509'}, {'text': 'hepatitis B surface antigen', 'type': 'Chemical', 'start': 333, 'end': 360, 'mesh': 'D006514'}, {'text': 'HBsAg', 'type': 'Chemical', 'start': 362, 'end': 367, 'mesh': 'D006514'}, {'text': 'hepatitis B e antigen', 'type': 'Chemical', 'start': 373, 'end': 394, 'mesh': 'D006513'}, {'text': 'HBeAg', 'type': 'Chemical', 'start': 396, 'end': 401, 'mesh': 'D006513'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 470, 'end': 481, 'mesh': 'D006509'}, {'text': 'hepatitis B vaccine', 'type': 'Chemical', 'start': 553, 'end': 572, 'mesh': 'D017325'}, {'text': 'HBsAg', 'type': 'Chemical', 'start': 789, 'end': 794, 'mesh': 'D006514'}, {'text': 'HBeAg', 'type': 'Chemical', 'start': 839, 'end': 844, 'mesh': 'D006513'}, {'text': 'HBsAg', 'type': 'Chemical', 'start': 862, 'end': 867, 'mesh': 'D006514'}, {'text': 'HBsAg', 'type': 'Chemical', 'start': 896, 'end': 901, 'mesh': 'D006514'}]"
+659,2322844,"Nociceptive effects induced by intrathecal administration of prostaglandin D2, E2, or F2 alpha to conscious mice.","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.","[{'text': 'prostaglandins', 'type': 'Chemical', 'start': 159, 'end': 173, 'mesh': 'D011453'}, {'text': 'pain', 'type': 'Disease', 'start': 177, 'end': 181, 'mesh': 'D010146'}, {'text': 'acetic acid', 'type': 'Chemical', 'start': 248, 'end': 259, 'mesh': 'D019342'}, {'text': 'Prostaglandin D2', 'type': 'Chemical', 'start': 276, 'end': 292, 'mesh': 'D015230'}, {'text': 'hyperalgesic', 'type': 'Disease', 'start': 316, 'end': 328, 'mesh': 'D006930'}, {'text': 'Prostaglandin E2', 'type': 'Chemical', 'start': 409, 'end': 425, 'mesh': 'D015232'}, {'text': 'hyperalgesic', 'type': 'Disease', 'start': 435, 'end': 447, 'mesh': 'D006930'}, {'text': 'pg', 'type': 'Chemical', 'start': 469, 'end': 471, 'mesh': 'D011453'}, {'text': 'prostaglandin D2', 'type': 'Chemical', 'start': 542, 'end': 558, 'mesh': 'D015230'}, {'text': 'acetic acid', 'type': 'Chemical', 'start': 593, 'end': 604, 'mesh': 'D019342'}, {'text': 'hyperalgesic', 'type': 'Disease', 'start': 625, 'end': 637, 'mesh': 'D006930'}, {'text': 'prostaglandin D2', 'type': 'Chemical', 'start': 648, 'end': 664, 'mesh': 'D015230'}, {'text': 'AH6809', 'type': 'Chemical', 'start': 776, 'end': 782, 'mesh': 'C053876'}, {'text': 'prostaglandin E2', 'type': 'Chemical', 'start': 834, 'end': 850, 'mesh': 'D015232'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 859, 'end': 871, 'mesh': 'D006930'}, {'text': 'AH6809', 'type': 'Chemical', 'start': 887, 'end': 893, 'mesh': 'C053876'}, {'text': 'Prostaglandin F2 alpha', 'type': 'Chemical', 'start': 967, 'end': 989, 'mesh': 'D015237'}, {'text': 'pain', 'type': 'Disease', 'start': 1011, 'end': 1015, 'mesh': 'D010146'}, {'text': 'prostaglandin D2', 'type': 'Chemical', 'start': 1063, 'end': 1079, 'mesh': 'D015230'}, {'text': 'prostaglandin E2', 'type': 'Chemical', 'start': 1084, 'end': 1100, 'mesh': 'D015232'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 1107, 'end': 1119, 'mesh': 'D006930'}]"
+660,20552622,Swallowing-induced atrial tachyarrhythmia triggered by salbutamol: case report and review of the literature.,"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.","[{'text': 'atrial tachyarrhythmia', 'type': 'Disease', 'start': 19, 'end': 41, 'mesh': 'D013617'}, {'text': 'salbutamol', 'type': 'Chemical', 'start': 55, 'end': 65, 'mesh': 'D000420'}, {'text': 'atrial tachyarrhythmia', 'type': 'Disease', 'start': 218, 'end': 240, 'mesh': 'D013617'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 340, 'end': 350, 'mesh': 'D001145'}, {'text': 'atenolol', 'type': 'Chemical', 'start': 379, 'end': 387, 'mesh': 'D001262'}, {'text': 'salbutamol', 'type': 'Chemical', 'start': 497, 'end': 507, 'mesh': 'D000420'}, {'text': 'atenolol', 'type': 'Chemical', 'start': 568, 'end': 576, 'mesh': 'D001262'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 582, 'end': 592, 'mesh': 'D001145'}, {'text': 'atrial tachyarrhythmia', 'type': 'Disease', 'start': 637, 'end': 659, 'mesh': 'D013617'}, {'text': 'SIAT', 'type': 'Disease', 'start': 661, 'end': 665, 'mesh': 'D013617'}, {'text': 'SIAT', 'type': 'Disease', 'start': 712, 'end': 716, 'mesh': 'D013617'}, {'text': 'SIAT', 'type': 'Disease', 'start': 878, 'end': 882, 'mesh': 'D013617'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 949, 'end': 959, 'mesh': 'D001145'}, {'text': 'SIAT', 'type': 'Disease', 'start': 986, 'end': 990, 'mesh': 'D013617'}, {'text': 'Salbutamol', 'type': 'Chemical', 'start': 1117, 'end': 1127, 'mesh': 'D000420'}, {'text': 'SIAT', 'type': 'Disease', 'start': 1172, 'end': 1176, 'mesh': 'D013617'}, {'text': 'salbutamol', 'type': 'Chemical', 'start': 1289, 'end': 1299, 'mesh': 'D000420'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 1317, 'end': 1328, 'mesh': 'D013610'}, {'text': 'atenolol', 'type': 'Chemical', 'start': 1450, 'end': 1458, 'mesh': 'D001262'}]"
+661,20510337,Coenzyme Q10 treatment ameliorates acute cisplatin nephrotoxicity in mice.,"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.","[{'text': 'Coenzyme Q10', 'type': 'Chemical', 'start': 0, 'end': 12, 'mesh': 'C024989'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 41, 'end': 50, 'mesh': 'D002945'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 51, 'end': 65, 'mesh': 'D007674'}, {'text': 'coenzyme Q10', 'type': 'Chemical', 'start': 106, 'end': 118, 'mesh': 'C024989'}, {'text': 'acute renal injury', 'type': 'Disease', 'start': 149, 'end': 167, 'mesh': 'D058186'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 206, 'end': 215, 'mesh': 'D002945'}, {'text': 'Coenzyme Q10', 'type': 'Chemical', 'start': 227, 'end': 239, 'mesh': 'C024989'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 329, 'end': 338, 'mesh': 'D002945'}, {'text': 'Coenzyme Q10', 'type': 'Chemical', 'start': 355, 'end': 367, 'mesh': 'C024989'}, {'text': 'blood urea nitrogen', 'type': 'Chemical', 'start': 390, 'end': 409, 'mesh': 'D001806'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 420, 'end': 430, 'mesh': 'D003404'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 462, 'end': 471, 'mesh': 'D002945'}, {'text': 'Coenzyme Q10', 'type': 'Chemical', 'start': 473, 'end': 485, 'mesh': 'C024989'}, {'text': 'reduced glutathione', 'type': 'Chemical', 'start': 560, 'end': 579, 'mesh': 'D005978'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 590, 'end': 600, 'mesh': 'D013481'}, {'text': 'tumor', 'type': 'Disease', 'start': 681, 'end': 686, 'mesh': 'D009369'}, {'text': 'necrosis', 'type': 'Disease', 'start': 687, 'end': 695, 'mesh': 'D009336'}, {'text': 'nitric oxide', 'type': 'Chemical', 'start': 710, 'end': 722, 'mesh': 'D009569'}, {'text': 'platinum', 'type': 'Chemical', 'start': 727, 'end': 735, 'mesh': 'D010984'}, {'text': 'selenium', 'type': 'Chemical', 'start': 788, 'end': 796, 'mesh': 'D012643'}, {'text': 'zinc', 'type': 'Chemical', 'start': 801, 'end': 805, 'mesh': 'D015032'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 841, 'end': 850, 'mesh': 'D002945'}, {'text': 'renal tissue damage', 'type': 'Disease', 'start': 891, 'end': 910, 'mesh': 'D007674'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 923, 'end': 932, 'mesh': 'D002945'}, {'text': 'coenzyme Q10', 'type': 'Chemical', 'start': 952, 'end': 964, 'mesh': 'C024989'}, {'text': 'coenzyme Q10', 'type': 'Chemical', 'start': 1019, 'end': 1031, 'mesh': 'C024989'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 1060, 'end': 1069, 'mesh': 'D002945'}, {'text': 'nitric oxide', 'type': 'Chemical', 'start': 1106, 'end': 1118, 'mesh': 'D009569'}, {'text': 'coenzyme Q10', 'type': 'Chemical', 'start': 1209, 'end': 1221, 'mesh': 'C024989'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 1289, 'end': 1298, 'mesh': 'D002945'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1299, 'end': 1313, 'mesh': 'D007674'}]"
+662,20164825,Metformin prevents experimental gentamicin-induced nephropathy by a mitochondria-dependent pathway.,"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.","[{'text': 'Metformin', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D008687'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 32, 'end': 42, 'mesh': 'D005839'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 51, 'end': 62, 'mesh': 'D007674'}, {'text': 'metformin', 'type': 'Chemical', 'start': 122, 'end': 131, 'mesh': 'D008687'}, {'text': 'vascular dysfunction', 'type': 'Disease', 'start': 216, 'end': 236, 'mesh': 'D014652'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 335, 'end': 345, 'mesh': 'D005839'}, {'text': 'toxicity', 'type': 'Disease', 'start': 346, 'end': 354, 'mesh': 'D064420'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 422, 'end': 428, 'mesh': 'D010100'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 521, 'end': 531, 'mesh': 'D005839'}, {'text': 'Metformin', 'type': 'Chemical', 'start': 548, 'end': 557, 'mesh': 'D008687'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 582, 'end': 592, 'mesh': 'D005839'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 602, 'end': 621, 'mesh': 'D058186'}, {'text': 'Metformin', 'type': 'Chemical', 'start': 784, 'end': 793, 'mesh': 'D008687'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 858, 'end': 868, 'mesh': 'D005839'}, {'text': 'kidney dysfunction', 'type': 'Disease', 'start': 910, 'end': 928, 'mesh': 'D007674'}, {'text': 'metformin', 'type': 'Chemical', 'start': 953, 'end': 962, 'mesh': 'D008687'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 1042, 'end': 1052, 'mesh': 'D005839'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 1234, 'end': 1240, 'mesh': 'D010100'}, {'text': 'metformin', 'type': 'Chemical', 'start': 1315, 'end': 1324, 'mesh': 'D008687'}, {'text': 'metformin', 'type': 'Chemical', 'start': 1379, 'end': 1388, 'mesh': 'D008687'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 1400, 'end': 1410, 'mesh': 'D005839'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1411, 'end': 1425, 'mesh': 'D007674'}]"
+663,20042557,Sedation depth during spinal anesthesia and the development of postoperative delirium in elderly patients undergoing hip fracture repair.,"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.","[{'text': 'hip fracture', 'type': 'Disease', 'start': 117, 'end': 129, 'mesh': 'D006620'}, {'text': 'hip fracture', 'type': 'Disease', 'start': 238, 'end': 250, 'mesh': 'D006620'}, {'text': 'delirium', 'type': 'Disease', 'start': 498, 'end': 506, 'mesh': 'D003693'}, {'text': 'dementia', 'type': 'Disease', 'start': 517, 'end': 525, 'mesh': 'D003704'}, {'text': 'hip fracture', 'type': 'Disease', 'start': 540, 'end': 552, 'mesh': 'D006620'}, {'text': 'propofol', 'type': 'Chemical', 'start': 589, 'end': 597, 'mesh': 'D015742'}, {'text': 'Mental Disorders', 'type': 'Disease', 'start': 904, 'end': 920, 'mesh': 'D001523'}, {'text': 'delirium', 'type': 'Disease', 'start': 1332, 'end': 1340, 'mesh': 'D003693'}, {'text': 'delirium', 'type': 'Disease', 'start': 1445, 'end': 1453, 'mesh': 'D003693'}, {'text': 'propofol', 'type': 'Chemical', 'start': 1619, 'end': 1627, 'mesh': 'D015742'}]"
+664,19944333,Sorafenib-induced acute myocardial infarction due to coronary artery spasm.,"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.","[{'text': 'Sorafenib', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'C471405'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 24, 'end': 45, 'mesh': 'D009203'}, {'text': 'coronary artery spasm', 'type': 'Disease', 'start': 53, 'end': 74, 'mesh': 'D003329'}, {'text': 'renal cell carcinoma', 'type': 'Disease', 'start': 108, 'end': 128, 'mesh': 'D002292'}, {'text': 'chest pain', 'type': 'Disease', 'start': 160, 'end': 170, 'mesh': 'D002637'}, {'text': 'sorafenib', 'type': 'Chemical', 'start': 212, 'end': 221, 'mesh': 'C471405'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 279, 'end': 300, 'mesh': 'D009203'}, {'text': 'subendocardial infarction', 'type': 'Disease', 'start': 397, 'end': 422, 'mesh': 'D009203'}, {'text': 'Coronary artery spasm', 'type': 'Disease', 'start': 492, 'end': 513, 'mesh': 'D003329'}, {'text': 'sorafenib', 'type': 'Chemical', 'start': 562, 'end': 571, 'mesh': 'C471405'}, {'text': 'Ca', 'type': 'Chemical', 'start': 594, 'end': 596, 'mesh': 'D002118'}, {'text': 'nitrates', 'type': 'Chemical', 'start': 617, 'end': 625, 'mesh': 'D009566'}, {'text': 'sorafenib', 'type': 'Chemical', 'start': 693, 'end': 702, 'mesh': 'C471405'}, {'text': 'nicorandil', 'type': 'Chemical', 'start': 721, 'end': 731, 'mesh': 'D020108'}, {'text': 'stable angina', 'type': 'Disease', 'start': 768, 'end': 781, 'mesh': 'D060050'}, {'text': 'sorafenib', 'type': 'Chemical', 'start': 818, 'end': 827, 'mesh': 'C471405'}, {'text': 'coronary artery spasm', 'type': 'Disease', 'start': 836, 'end': 857, 'mesh': 'D003329'}, {'text': 'Sorafenib', 'type': 'Chemical', 'start': 859, 'end': 868, 'mesh': 'C471405'}, {'text': 'coronary artery spasm', 'type': 'Disease', 'start': 1064, 'end': 1085, 'mesh': 'D003329'}, {'text': 'sorafenib', 'type': 'Chemical', 'start': 1152, 'end': 1161, 'mesh': 'C471405'}]"
+665,17975693,Anxiogenic potential of ciprofloxacin and norfloxacin in rats.,"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.","[{'text': 'ciprofloxacin', 'type': 'Chemical', 'start': 24, 'end': 37, 'mesh': 'D002939'}, {'text': 'norfloxacin', 'type': 'Chemical', 'start': 42, 'end': 53, 'mesh': 'D009643'}, {'text': 'fluoroquinolones', 'type': 'Chemical', 'start': 112, 'end': 128, 'mesh': 'D024841'}, {'text': 'ciprofloxacin', 'type': 'Chemical', 'start': 137, 'end': 150, 'mesh': 'D002939'}, {'text': 'norfloxacin', 'type': 'Chemical', 'start': 155, 'end': 166, 'mesh': 'D009643'}, {'text': 'ciprofloxacin', 'type': 'Chemical', 'start': 595, 'end': 608, 'mesh': 'D002939'}, {'text': 'norfloxacin', 'type': 'Chemical', 'start': 614, 'end': 625, 'mesh': 'D009643'}, {'text': 'anxious behaviour', 'type': 'Disease', 'start': 646, 'end': 663, 'mesh': 'D001008'}, {'text': 'ciprofloxacin', 'type': 'Chemical', 'start': 734, 'end': 747, 'mesh': 'D002939'}, {'text': 'norfloxacin', 'type': 'Chemical', 'start': 753, 'end': 764, 'mesh': 'D009643'}, {'text': 'ciprofloxacin', 'type': 'Chemical', 'start': 965, 'end': 978, 'mesh': 'D002939'}, {'text': 'norfloxacin', 'type': 'Chemical', 'start': 983, 'end': 994, 'mesh': 'D009643'}]"
+666,17943461,Myocardial Fas ligand expression increases susceptibility to AZT-induced cardiomyopathy.,"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.","[{'text': 'AZT', 'type': 'Chemical', 'start': 61, 'end': 64, 'mesh': 'D015215'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 73, 'end': 87, 'mesh': 'D009202'}, {'text': 'Dilated cardiomyopathy', 'type': 'Disease', 'start': 101, 'end': 123, 'mesh': 'D002311'}, {'text': 'DCM', 'type': 'Disease', 'start': 125, 'end': 128, 'mesh': 'D002311'}, {'text': 'myocarditis', 'type': 'Disease', 'start': 134, 'end': 145, 'mesh': 'D009205'}, {'text': 'HIV-infected', 'type': 'Disease', 'start': 160, 'end': 172, 'mesh': 'D015658'}, {'text': 'heart failure', 'type': 'Disease', 'start': 211, 'end': 224, 'mesh': 'D006333'}, {'text': 'acquired immunodeficiency syndrome', 'type': 'Disease', 'start': 348, 'end': 382, 'mesh': 'D000163'}, {'text': 'AIDS', 'type': 'Disease', 'start': 384, 'end': 388, 'mesh': 'D000163'}, {'text': 'cardiac and skeletal myopathies', 'type': 'Disease', 'start': 426, 'end': 457, 'mesh': 'C538496'}, {'text': 'zidovudine', 'type': 'Chemical', 'start': 532, 'end': 542, 'mesh': 'D015215'}, {'text': ""3'-azido-2',3'-deoxythymidine"", 'type': 'Chemical', 'start': 544, 'end': 573, 'mesh': 'D015215'}, {'text': 'AZT', 'type': 'Chemical', 'start': 575, 'end': 578, 'mesh': 'D015215'}, {'text': 'DCM', 'type': 'Disease', 'start': 681, 'end': 684, 'mesh': 'D002311'}, {'text': 'AZT', 'type': 'Chemical', 'start': 854, 'end': 857, 'mesh': 'D015215'}, {'text': 'AZT', 'type': 'Chemical', 'start': 1139, 'end': 1142, 'mesh': 'D015215'}, {'text': 'cardiac dilation', 'type': 'Disease', 'start': 1174, 'end': 1190, 'mesh': 'D002311'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 1840, 'end': 1854, 'mesh': 'D009202'}]"
+667,17074608,Valproate-induced chorea and encephalopathy in atypical nonketotic hyperglycinemia.,"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.","[{'text': 'Valproate', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D014635'}, {'text': 'chorea', 'type': 'Disease', 'start': 18, 'end': 24, 'mesh': 'D002819'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 29, 'end': 43, 'mesh': 'D001927'}, {'text': 'nonketotic hyperglycinemia', 'type': 'Disease', 'start': 56, 'end': 82, 'mesh': 'D020158'}, {'text': 'Nonketotic hyperglycinemia', 'type': 'Disease', 'start': 84, 'end': 110, 'mesh': 'D020158'}, {'text': 'disorder of amino acid metabolism', 'type': 'Disease', 'start': 116, 'end': 149, 'mesh': 'D000592'}, {'text': 'glycine', 'type': 'Chemical', 'start': 175, 'end': 182, 'mesh': 'D005998'}, {'text': 'glycine', 'type': 'Chemical', 'start': 227, 'end': 234, 'mesh': 'D005998'}, {'text': 'apnea', 'type': 'Disease', 'start': 323, 'end': 328, 'mesh': 'D001049'}, {'text': 'seizures', 'type': 'Disease', 'start': 342, 'end': 350, 'mesh': 'D012640'}, {'text': 'hypotonia', 'type': 'Disease', 'start': 356, 'end': 365, 'mesh': 'D009123'}, {'text': 'psychomotor retardation', 'type': 'Disease', 'start': 391, 'end': 414, 'mesh': 'D011596'}, {'text': 'nonketotic hyperglycinemia', 'type': 'Disease', 'start': 453, 'end': 479, 'mesh': 'D020158'}, {'text': 'language delay', 'type': 'Disease', 'start': 583, 'end': 597, 'mesh': 'D007805'}, {'text': 'mental retardation', 'type': 'Disease', 'start': 602, 'end': 620, 'mesh': 'D008607'}, {'text': 'nonketotic hyperglycinemia', 'type': 'Disease', 'start': 644, 'end': 670, 'mesh': 'D020158'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 709, 'end': 723, 'mesh': 'D001927'}, {'text': 'chorea', 'type': 'Disease', 'start': 728, 'end': 734, 'mesh': 'D002819'}, {'text': 'valproate', 'type': 'Chemical', 'start': 763, 'end': 772, 'mesh': 'D014635'}]"
+668,16364460,Microinjection of ritanserin into the CA1 region of hippocampus improves scopolamine-induced amnesia in adult male rats.,"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.","[{'text': 'ritanserin', 'type': 'Chemical', 'start': 18, 'end': 28, 'mesh': 'D016713'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 73, 'end': 84, 'mesh': 'D012601'}, {'text': 'amnesia', 'type': 'Disease', 'start': 93, 'end': 100, 'mesh': 'D000647'}, {'text': 'ritanserin', 'type': 'Chemical', 'start': 135, 'end': 145, 'mesh': 'D016713'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 168, 'end': 179, 'mesh': 'D012601'}, {'text': 'amnesia', 'type': 'Disease', 'start': 224, 'end': 231, 'mesh': 'D000647'}, {'text': 'DMSO', 'type': 'Chemical', 'start': 435, 'end': 439, 'mesh': 'D004121'}, {'text': 'DMSO', 'type': 'Chemical', 'start': 448, 'end': 452, 'mesh': 'D004121'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 455, 'end': 466, 'mesh': 'D012601'}, {'text': 'ritanserin', 'type': 'Chemical', 'start': 526, 'end': 536, 'mesh': 'D016713'}, {'text': 'DMSO', 'type': 'Chemical', 'start': 567, 'end': 571, 'mesh': 'D004121'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 606, 'end': 617, 'mesh': 'D012601'}, {'text': 'ritanserin', 'type': 'Chemical', 'start': 654, 'end': 664, 'mesh': 'D016713'}, {'text': 'ritanserin', 'type': 'Chemical', 'start': 676, 'end': 686, 'mesh': 'D016713'}, {'text': 'DMSO', 'type': 'Chemical', 'start': 708, 'end': 712, 'mesh': 'D004121'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 1129, 'end': 1140, 'mesh': 'D012601'}, {'text': 'Ritanserin', 'type': 'Chemical', 'start': 1184, 'end': 1194, 'mesh': 'D016713'}, {'text': 'DMSO', 'type': 'Chemical', 'start': 1308, 'end': 1312, 'mesh': 'D004121'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 1337, 'end': 1348, 'mesh': 'D012601'}, {'text': 'ritanserin', 'type': 'Chemical', 'start': 1353, 'end': 1363, 'mesh': 'D016713'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 1479, 'end': 1490, 'mesh': 'D012601'}, {'text': 'ritanserin', 'type': 'Chemical', 'start': 1546, 'end': 1556, 'mesh': 'D016713'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 1609, 'end': 1620, 'mesh': 'D012601'}, {'text': 'amnesia', 'type': 'Disease', 'start': 1629, 'end': 1636, 'mesh': 'D000647'}]"
+669,15579441,Hypoxia in renal disease with proteinuria and/or glomerular hypertension.,"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.","[{'text': 'Hypoxia', 'type': 'Disease', 'start': 0, 'end': 7, 'mesh': 'D000860'}, {'text': 'renal disease', 'type': 'Disease', 'start': 11, 'end': 24, 'mesh': 'D007674'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 30, 'end': 41, 'mesh': 'D011507'}, {'text': 'hypertension', 'type': 'Disease', 'start': 60, 'end': 72, 'mesh': 'D006973'}, {'text': 'hypoxia', 'type': 'Disease', 'start': 247, 'end': 254, 'mesh': 'D000860'}, {'text': 'hypoxia', 'type': 'Disease', 'start': 290, 'end': 297, 'mesh': 'D000860'}, {'text': 'hypoxia', 'type': 'Disease', 'start': 404, 'end': 411, 'mesh': 'D000860'}, {'text': 'hypoxia', 'type': 'Disease', 'start': 509, 'end': 516, 'mesh': 'D000860'}, {'text': 'diseased kidney', 'type': 'Disease', 'start': 524, 'end': 539, 'mesh': 'D007674'}, {'text': 'hypoxia', 'type': 'Disease', 'start': 600, 'end': 607, 'mesh': 'D000860'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 615, 'end': 640, 'mesh': 'D011692'}, {'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 649, 'end': 667, 'mesh': 'D009404'}, {'text': 'hypoxia', 'type': 'Disease', 'start': 692, 'end': 699, 'mesh': 'D000860'}, {'text': 'hypoxia', 'type': 'Disease', 'start': 747, 'end': 754, 'mesh': 'D000860'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 857, 'end': 882, 'mesh': 'D011692'}, {'text': 'hypoxia', 'type': 'Disease', 'start': 1079, 'end': 1086, 'mesh': 'D000860'}, {'text': 'tubulointerstitial injury', 'type': 'Disease', 'start': 1134, 'end': 1159, 'mesh': '-1'}, {'text': 'hypoxic', 'type': 'Disease', 'start': 1336, 'end': 1343, 'mesh': 'D000860'}, {'text': 'hypoxia', 'type': 'Disease', 'start': 1466, 'end': 1473, 'mesh': 'D000860'}, {'text': 'glomerular diseases', 'type': 'Disease', 'start': 1490, 'end': 1509, 'mesh': 'D007674'}]"
+670,15517007,"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.","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.","[{'text': 'cardiotoxicity', 'type': 'Disease', 'start': 31, 'end': 45, 'mesh': 'D066126'}, {'text': 'autoimmune diseases', 'type': 'Disease', 'start': 124, 'end': 143, 'mesh': 'D001327'}, {'text': 'systemic sclerosis', 'type': 'Disease', 'start': 171, 'end': 189, 'mesh': 'D012595'}, {'text': 'multiple sclerosis', 'type': 'Disease', 'start': 194, 'end': 212, 'mesh': 'D009103'}, {'text': 'autoimmune diseases', 'type': 'Disease', 'start': 342, 'end': 361, 'mesh': 'D001327'}, {'text': 'infections', 'type': 'Disease', 'start': 742, 'end': 752, 'mesh': 'D007239'}, {'text': 'cardiac toxicity', 'type': 'Disease', 'start': 786, 'end': 802, 'mesh': 'D066126'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 845, 'end': 861, 'mesh': 'D003520'}, {'text': 'anthracyclines', 'type': 'Chemical', 'start': 865, 'end': 879, 'mesh': 'D018943'}, {'text': 'mitoxantrone', 'type': 'Chemical', 'start': 888, 'end': 900, 'mesh': 'D008942'}, {'text': 'heart damage', 'type': 'Disease', 'start': 949, 'end': 961, 'mesh': 'D006331'}, {'text': 'systemic sclerosis', 'type': 'Disease', 'start': 976, 'end': 994, 'mesh': 'D012595'}, {'text': 'autoimmune disease', 'type': 'Disease', 'start': 1346, 'end': 1364, 'mesh': 'D001327'}]"
+671,12180796,"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.","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.","[{'text': 'nitric oxide', 'type': 'Chemical', 'start': 47, 'end': 59, 'mesh': 'D009569'}, {'text': 'tumor', 'type': 'Disease', 'start': 110, 'end': 115, 'mesh': 'D009369'}, {'text': 'arteritis', 'type': 'Disease', 'start': 151, 'end': 160, 'mesh': 'D001167'}, {'text': 'fenoldopam', 'type': 'Chemical', 'start': 180, 'end': 190, 'mesh': 'D018818'}, {'text': 'theophylline', 'type': 'Chemical', 'start': 195, 'end': 207, 'mesh': 'D013806'}, {'text': 'Arteritis', 'type': 'Disease', 'start': 223, 'end': 232, 'mesh': 'D001167'}, {'text': 'fenoldopam', 'type': 'Chemical', 'start': 266, 'end': 276, 'mesh': 'D018818'}, {'text': 'theophylline', 'type': 'Chemical', 'start': 281, 'end': 293, 'mesh': 'D013806'}, {'text': 'nitric oxide', 'type': 'Chemical', 'start': 367, 'end': 379, 'mesh': 'D009569'}, {'text': 'tumor', 'type': 'Disease', 'start': 439, 'end': 444, 'mesh': 'D009369'}, {'text': 'fenoldopam', 'type': 'Chemical', 'start': 501, 'end': 511, 'mesh': 'D018818'}, {'text': 'theophylline', 'type': 'Chemical', 'start': 614, 'end': 626, 'mesh': 'D013806'}, {'text': 'theophylline', 'type': 'Chemical', 'start': 644, 'end': 656, 'mesh': 'D013806'}, {'text': 'fenoldopam', 'type': 'Chemical', 'start': 755, 'end': 765, 'mesh': 'D018818'}, {'text': 'arteritis', 'type': 'Disease', 'start': 1108, 'end': 1117, 'mesh': 'D001167'}]"
+672,12109865,Low-molecular-weight heparin for the treatment of patients with mechanical heart valves.,"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.","[{'text': 'Low-molecular-weight heparin', 'type': 'Chemical', 'start': 0, 'end': 28, 'mesh': 'D006495'}, {'text': 'Unfractionated heparin', 'type': 'Chemical', 'start': 303, 'end': 325, 'mesh': 'D006493'}, {'text': 'UH', 'type': 'Chemical', 'start': 327, 'end': 329, 'mesh': 'D006493'}, {'text': 'Low-molecular-weight heparin', 'type': 'Chemical', 'start': 382, 'end': 410, 'mesh': 'D006495'}, {'text': 'LMWH', 'type': 'Chemical', 'start': 412, 'end': 416, 'mesh': 'D006495'}, {'text': 'UH', 'type': 'Chemical', 'start': 453, 'end': 455, 'mesh': 'D006493'}, {'text': 'UH', 'type': 'Chemical', 'start': 533, 'end': 535, 'mesh': 'D006493'}, {'text': 'LMWH', 'type': 'Chemical', 'start': 669, 'end': 673, 'mesh': 'D006495'}, {'text': 'LMWH', 'type': 'Chemical', 'start': 813, 'end': 817, 'mesh': 'D006495'}, {'text': 'thromboembolic', 'type': 'Disease', 'start': 1028, 'end': 1042, 'mesh': 'D013923'}, {'text': 'thromboembolism', 'type': 'Disease', 'start': 1378, 'end': 1393, 'mesh': 'D013923'}, {'text': 'hemorrhage', 'type': 'Disease', 'start': 1490, 'end': 1500, 'mesh': 'D006470'}, {'text': 'LMWH', 'type': 'Chemical', 'start': 1644, 'end': 1648, 'mesh': 'D006495'}, {'text': 'UH', 'type': 'Chemical', 'start': 1681, 'end': 1683, 'mesh': 'D006493'}, {'text': 'LMWH', 'type': 'Chemical', 'start': 1712, 'end': 1716, 'mesh': 'D006495'}, {'text': 'LMWH', 'type': 'Chemical', 'start': 1861, 'end': 1865, 'mesh': 'D006495'}]"
+673,12042105,Topiramate-induced nephrolithiasis.,"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.","[{'text': 'Topiramate', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'C052342'}, {'text': 'nephrolithiasis', 'type': 'Disease', 'start': 19, 'end': 34, 'mesh': 'D053040'}, {'text': 'Topiramate', 'type': 'Chemical', 'start': 36, 'end': 46, 'mesh': 'C052342'}, {'text': 'refractory seizures', 'type': 'Disease', 'start': 172, 'end': 191, 'mesh': 'D004827'}, {'text': 'metabolic acidosis', 'type': 'Disease', 'start': 251, 'end': 269, 'mesh': 'D000138'}, {'text': 'calcium phosphate', 'type': 'Chemical', 'start': 494, 'end': 511, 'mesh': 'C020243'}, {'text': 'nephrolithiasis', 'type': 'Disease', 'start': 512, 'end': 527, 'mesh': 'D053040'}, {'text': 'topiramate', 'type': 'Chemical', 'start': 562, 'end': 572, 'mesh': 'C052342'}, {'text': 'nephrolithiasis', 'type': 'Disease', 'start': 581, 'end': 596, 'mesh': 'D053040'}]"
+674,11868798,Spironolactone: is it a novel drug for the prevention of amphotericin B-related hypokalemia in cancer patients?,"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.","[{'text': 'Spironolactone', 'type': 'Chemical', 'start': 0, 'end': 14, 'mesh': 'D013148'}, {'text': 'amphotericin B', 'type': 'Chemical', 'start': 57, 'end': 71, 'mesh': 'D000666'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 80, 'end': 91, 'mesh': 'D007008'}, {'text': 'cancer', 'type': 'Disease', 'start': 95, 'end': 101, 'mesh': 'D009369'}, {'text': 'Nephrotoxicity', 'type': 'Disease', 'start': 123, 'end': 137, 'mesh': 'D007674'}, {'text': 'amphotericin B', 'type': 'Chemical', 'start': 169, 'end': 183, 'mesh': 'D000666'}, {'text': 'AmB', 'type': 'Chemical', 'start': 185, 'end': 188, 'mesh': 'D000666'}, {'text': 'toxicity', 'type': 'Disease', 'start': 273, 'end': 281, 'mesh': 'D064420'}, {'text': 'potassium', 'type': 'Chemical', 'start': 323, 'end': 332, 'mesh': 'D011188'}, {'text': 'AmB', 'type': 'Chemical', 'start': 396, 'end': 399, 'mesh': 'D000666'}, {'text': 'Potassium', 'type': 'Chemical', 'start': 401, 'end': 410, 'mesh': 'D011188'}, {'text': 'toxicity', 'type': 'Disease', 'start': 450, 'end': 458, 'mesh': 'D064420'}, {'text': 'AmB', 'type': 'Chemical', 'start': 462, 'end': 465, 'mesh': 'D000666'}, {'text': 'spironolactone', 'type': 'Chemical', 'start': 516, 'end': 530, 'mesh': 'D013148'}, {'text': 'potassium', 'type': 'Chemical', 'start': 541, 'end': 550, 'mesh': 'D011188'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 579, 'end': 590, 'mesh': 'D007008'}, {'text': 'neutropenic', 'type': 'Disease', 'start': 594, 'end': 605, 'mesh': 'D009503'}, {'text': 'AmB', 'type': 'Chemical', 'start': 618, 'end': 621, 'mesh': 'D000666'}, {'text': 'hematological disorders', 'type': 'Disease', 'start': 681, 'end': 704, 'mesh': 'D006402'}, {'text': 'AmB', 'type': 'Chemical', 'start': 751, 'end': 754, 'mesh': 'D000666'}, {'text': 'AmB', 'type': 'Chemical', 'start': 764, 'end': 767, 'mesh': 'D000666'}, {'text': 'spironolactone', 'type': 'Chemical', 'start': 777, 'end': 791, 'mesh': 'D013148'}, {'text': 'fungal infection', 'type': 'Disease', 'start': 849, 'end': 865, 'mesh': 'D009181'}, {'text': 'AmB', 'type': 'Chemical', 'start': 907, 'end': 910, 'mesh': 'D000666'}, {'text': 'spironolactone', 'type': 'Chemical', 'start': 915, 'end': 929, 'mesh': 'D013148'}, {'text': 'potassium', 'type': 'Chemical', 'start': 962, 'end': 971, 'mesh': 'D011188'}, {'text': 'AmB', 'type': 'Chemical', 'start': 1000, 'end': 1003, 'mesh': 'D000666'}, {'text': 'AmB', 'type': 'Chemical', 'start': 1049, 'end': 1052, 'mesh': 'D000666'}, {'text': 'spironolactone', 'type': 'Chemical', 'start': 1057, 'end': 1071, 'mesh': 'D013148'}, {'text': 'potassium', 'type': 'Chemical', 'start': 1100, 'end': 1109, 'mesh': 'D011188'}, {'text': 'potassium', 'type': 'Chemical', 'start': 1151, 'end': 1160, 'mesh': 'D011188'}, {'text': 'potassium', 'type': 'Chemical', 'start': 1216, 'end': 1225, 'mesh': 'D011188'}, {'text': 'AmB', 'type': 'Chemical', 'start': 1279, 'end': 1282, 'mesh': 'D000666'}, {'text': 'spironolactone', 'type': 'Chemical', 'start': 1287, 'end': 1301, 'mesh': 'D013148'}, {'text': 'AmB', 'type': 'Chemical', 'start': 1323, 'end': 1326, 'mesh': 'D000666'}, {'text': 'spironolactone', 'type': 'Chemical', 'start': 1381, 'end': 1395, 'mesh': 'D013148'}, {'text': 'potassium', 'type': 'Chemical', 'start': 1407, 'end': 1416, 'mesh': 'D011188'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 1442, 'end': 1453, 'mesh': 'D007008'}, {'text': 'potassium', 'type': 'Chemical', 'start': 1474, 'end': 1483, 'mesh': 'D011188'}, {'text': 'neutropenic', 'type': 'Disease', 'start': 1492, 'end': 1503, 'mesh': 'D009503'}, {'text': 'AmB', 'type': 'Chemical', 'start': 1516, 'end': 1519, 'mesh': 'D000666'}]"
+675,11860278,Dopamine D2 receptor signaling controls neuronal cell death induced by muscarinic and glutamatergic drugs.,"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.","[{'text': 'Dopamine', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D004298'}, {'text': 'Dopamine', 'type': 'Chemical', 'start': 107, 'end': 115, 'mesh': 'D004298'}, {'text': 'DA', 'type': 'Chemical', 'start': 117, 'end': 119, 'mesh': 'D004298'}, {'text': 'epileptic seizures', 'type': 'Disease', 'start': 202, 'end': 220, 'mesh': 'D004827'}, {'text': 'Excitotoxicity', 'type': 'Disease', 'start': 251, 'end': 265, 'mesh': '-1'}, {'text': 'seizures', 'type': 'Disease', 'start': 345, 'end': 353, 'mesh': 'D012640'}, {'text': 'DA', 'type': 'Chemical', 'start': 428, 'end': 430, 'mesh': 'D004298'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 462, 'end': 470, 'mesh': 'D004827'}, {'text': 'seizures', 'type': 'Disease', 'start': 534, 'end': 542, 'mesh': 'D012640'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 547, 'end': 560, 'mesh': 'D020258'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 614, 'end': 625, 'mesh': 'D010862'}, {'text': 'kainic acid', 'type': 'Chemical', 'start': 689, 'end': 700, 'mesh': 'D007608'}, {'text': 'KA', 'type': 'Chemical', 'start': 702, 'end': 704, 'mesh': 'D007608'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 716, 'end': 725, 'mesh': 'D018698'}, {'text': 'seizures', 'type': 'Disease', 'start': 769, 'end': 777, 'mesh': 'D012640'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 864, 'end': 877, 'mesh': 'D020258'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 888, 'end': 899, 'mesh': 'D010862'}, {'text': 'seizures', 'type': 'Disease', 'start': 908, 'end': 916, 'mesh': 'D012640'}, {'text': 'KA', 'type': 'Chemical', 'start': 1007, 'end': 1009, 'mesh': 'D007608'}, {'text': 'seizures', 'type': 'Disease', 'start': 1061, 'end': 1069, 'mesh': 'D012640'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 1086, 'end': 1095, 'mesh': 'D018698'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 1100, 'end': 1113, 'mesh': 'D000109'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 1153, 'end': 1161, 'mesh': 'D004827'}, {'text': 'neurodegeneration', 'type': 'Disease', 'start': 1170, 'end': 1187, 'mesh': 'D019636'}]"
+676,11838826,Treatment of risperidone-induced hyperprolactinemia with a dopamine agonist in children.,"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.","[{'text': 'risperidone', 'type': 'Chemical', 'start': 13, 'end': 24, 'mesh': 'D018967'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 33, 'end': 51, 'mesh': 'D006966'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 59, 'end': 67, 'mesh': 'D004298'}, {'text': 'Risperidone', 'type': 'Chemical', 'start': 101, 'end': 112, 'mesh': 'D018967'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 212, 'end': 230, 'mesh': 'D006966'}, {'text': 'prolactinomas', 'type': 'Disease', 'start': 310, 'end': 323, 'mesh': 'D015175'}, {'text': 'delayed puberty', 'type': 'Disease', 'start': 399, 'end': 414, 'mesh': 'D011628'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 535, 'end': 553, 'mesh': 'D006966'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 602, 'end': 613, 'mesh': 'D018967'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 622, 'end': 640, 'mesh': 'D006966'}, {'text': 'cabergoline', 'type': 'Chemical', 'start': 646, 'end': 657, 'mesh': 'C047047'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 740, 'end': 751, 'mesh': 'D018967'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 760, 'end': 778, 'mesh': 'D006966'}, {'text': 'cabergoline', 'type': 'Chemical', 'start': 792, 'end': 803, 'mesh': 'C047047'}, {'text': 'Mental Disorders', 'type': 'Disease', 'start': 884, 'end': 900, 'mesh': 'D001523'}, {'text': 'bipolar disorder', 'type': 'Disease', 'start': 918, 'end': 934, 'mesh': 'D001714'}, {'text': 'psychoses', 'type': 'Disease', 'start': 938, 'end': 947, 'mesh': 'D011605'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 954, 'end': 965, 'mesh': 'D018967'}, {'text': 'cabergoline', 'type': 'Chemical', 'start': 1066, 'end': 1077, 'mesh': 'C047047'}, {'text': 'cabergoline', 'type': 'Chemical', 'start': 1205, 'end': 1216, 'mesh': 'C047047'}, {'text': 'cabergoline', 'type': 'Chemical', 'start': 1308, 'end': 1319, 'mesh': 'C047047'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 1384, 'end': 1395, 'mesh': 'D018967'}, {'text': 'Cabergoline', 'type': 'Chemical', 'start': 1422, 'end': 1433, 'mesh': 'C047047'}, {'text': 'Cabergoline', 'type': 'Chemical', 'start': 1491, 'end': 1502, 'mesh': 'C047047'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 1538, 'end': 1549, 'mesh': 'D018967'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 1558, 'end': 1576, 'mesh': 'D006966'}]"
+677,11467664,Cholestatic jaundice associated with the use of metformin.,"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.","[{'text': 'Cholestatic jaundice', 'type': 'Disease', 'start': 0, 'end': 20, 'mesh': 'D041781'}, {'text': 'metformin', 'type': 'Chemical', 'start': 48, 'end': 57, 'mesh': 'D008687'}, {'text': 'cholestatic jaundice', 'type': 'Disease', 'start': 93, 'end': 113, 'mesh': 'D041781'}, {'text': 'metformin hydrochloride', 'type': 'Chemical', 'start': 157, 'end': 180, 'mesh': 'D008687'}, {'text': 'cholestasis', 'type': 'Disease', 'start': 331, 'end': 342, 'mesh': 'D002779'}, {'text': 'edema', 'type': 'Disease', 'start': 356, 'end': 361, 'mesh': 'D004487'}, {'text': 'inflammation', 'type': 'Disease', 'start': 397, 'end': 409, 'mesh': 'D007249'}, {'text': 'Metformin hydrochloride', 'type': 'Chemical', 'start': 411, 'end': 434, 'mesh': 'D008687'}, {'text': 'jaundice', 'type': 'Disease', 'start': 471, 'end': 479, 'mesh': 'D007565'}, {'text': 'jaundice', 'type': 'Disease', 'start': 552, 'end': 560, 'mesh': 'D007565'}, {'text': 'metformin', 'type': 'Chemical', 'start': 590, 'end': 599, 'mesh': 'D008687'}, {'text': 'metformin', 'type': 'Chemical', 'start': 652, 'end': 661, 'mesh': 'D008687'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 673, 'end': 687, 'mesh': 'D056486'}]"
+678,11077455,"Electro-oculography, electroretinography, visual evoked potentials, and multifocal electroretinography in patients with vigabatrin-attributed visual field constriction.","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.","[{'text': 'vigabatrin', 'type': 'Chemical', 'start': 120, 'end': 130, 'mesh': 'D020888'}, {'text': 'visual field constriction', 'type': 'Disease', 'start': 142, 'end': 167, 'mesh': 'D014786'}, {'text': 'visual field constriction', 'type': 'Disease', 'start': 190, 'end': 215, 'mesh': 'D014786'}, {'text': 'vigabatrin', 'type': 'Chemical', 'start': 246, 'end': 256, 'mesh': 'D020888'}, {'text': 'vigabatrin', 'type': 'Chemical', 'start': 383, 'end': 393, 'mesh': 'D020888'}, {'text': 'visual field loss', 'type': 'Disease', 'start': 405, 'end': 422, 'mesh': 'D014786'}, {'text': 'vigabatrin', 'type': 'Chemical', 'start': 509, 'end': 519, 'mesh': 'D020888'}, {'text': 'visual field constriction', 'type': 'Disease', 'start': 884, 'end': 909, 'mesh': 'D014786'}, {'text': 'visual field constriction', 'type': 'Disease', 'start': 1497, 'end': 1522, 'mesh': 'D014786'}, {'text': 'vigabatrin', 'type': 'Chemical', 'start': 1553, 'end': 1563, 'mesh': 'D020888'}, {'text': 'vigabatrin', 'type': 'Chemical', 'start': 1648, 'end': 1658, 'mesh': 'D020888'}]"
+679,11063349,Conversion to rapamycin immunosuppression in renal transplant recipients: report of an initial experience.,"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.","[{'text': 'rapamycin', 'type': 'Chemical', 'start': 14, 'end': 23, 'mesh': 'D020123'}, {'text': 'RAPA', 'type': 'Chemical', 'start': 171, 'end': 175, 'mesh': 'D020123'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 210, 'end': 222, 'mesh': 'D016572'}, {'text': 'CsA', 'type': 'Chemical', 'start': 224, 'end': 227, 'mesh': 'D016572'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 232, 'end': 242, 'mesh': 'D016559'}, {'text': 'Tac', 'type': 'Chemical', 'start': 244, 'end': 247, 'mesh': 'D016559'}, {'text': 'toxicity', 'type': 'Disease', 'start': 249, 'end': 257, 'mesh': 'D064420'}, {'text': 'rapamycin', 'type': 'Chemical', 'start': 331, 'end': 340, 'mesh': 'D020123'}, {'text': 'RAPA', 'type': 'Chemical', 'start': 342, 'end': 346, 'mesh': 'D020123'}, {'text': 'CsA', 'type': 'Chemical', 'start': 487, 'end': 490, 'mesh': 'D016572'}, {'text': 'Tac', 'type': 'Chemical', 'start': 494, 'end': 497, 'mesh': 'D016559'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 498, 'end': 512, 'mesh': 'D007674'}, {'text': 'CsA', 'type': 'Chemical', 'start': 525, 'end': 528, 'mesh': 'D016572'}, {'text': 'Tac', 'type': 'Chemical', 'start': 532, 'end': 535, 'mesh': 'D016559'}, {'text': 'toxicity', 'type': 'Disease', 'start': 536, 'end': 544, 'mesh': 'D064420'}, {'text': 'facial dysmorphism', 'type': 'Disease', 'start': 557, 'end': 575, 'mesh': '-1'}, {'text': 'posttransplant lymphoproliferative disorder', 'type': 'Disease', 'start': 581, 'end': 624, 'mesh': 'D008232'}, {'text': 'PTLD', 'type': 'Disease', 'start': 626, 'end': 630, 'mesh': 'D008232'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 654, 'end': 668, 'mesh': 'D056486'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 760, 'end': 774, 'mesh': 'D007674'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 817, 'end': 827, 'mesh': 'D003404'}, {'text': 'Facial dysmorphism', 'type': 'Disease', 'start': 888, 'end': 906, 'mesh': '-1'}, {'text': 'PTLD', 'type': 'Disease', 'start': 947, 'end': 951, 'mesh': 'D008232'}, {'text': 'pneumonia', 'type': 'Disease', 'start': 990, 'end': 999, 'mesh': 'D011014'}, {'text': 'Pneumocystis carinii pneumonia', 'type': 'Disease', 'start': 1005, 'end': 1035, 'mesh': 'D011020'}, {'text': 'infectious mononucleosis', 'type': 'Disease', 'start': 1041, 'end': 1065, 'mesh': 'D007244'}, {'text': 'PTLD', 'type': 'Disease', 'start': 1082, 'end': 1086, 'mesh': 'D008232'}, {'text': 'bronchiolitis obliterans', 'type': 'Disease', 'start': 1116, 'end': 1140, 'mesh': 'D001989'}, {'text': 'RAPA', 'type': 'Chemical', 'start': 1164, 'end': 1168, 'mesh': 'D020123'}, {'text': 'pneumonia', 'type': 'Disease', 'start': 1215, 'end': 1224, 'mesh': 'D011014'}, {'text': 'PTLD', 'type': 'Disease', 'start': 1233, 'end': 1237, 'mesh': 'D008232'}, {'text': 'aphtous ulcers', 'type': 'Disease', 'start': 1255, 'end': 1269, 'mesh': 'D013281'}, {'text': 'RAPA', 'type': 'Chemical', 'start': 1278, 'end': 1282, 'mesh': 'D020123'}, {'text': 'RAPA', 'type': 'Chemical', 'start': 1352, 'end': 1356, 'mesh': 'D020123'}, {'text': 'CsA', 'type': 'Chemical', 'start': 1414, 'end': 1417, 'mesh': 'D016572'}, {'text': 'RAPA', 'type': 'Chemical', 'start': 1467, 'end': 1471, 'mesh': 'D020123'}, {'text': 'Pneumocystis carinii pneumonia', 'type': 'Disease', 'start': 1563, 'end': 1593, 'mesh': 'D011020'}]"
+680,10091616,Worsening of levodopa-induced dyskinesias by motor and mental tasks.,"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.","[{'text': 'levodopa', 'type': 'Chemical', 'start': 13, 'end': 21, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 30, 'end': 41, 'mesh': 'D004409'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 90, 'end': 109, 'mesh': 'D010300'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 125, 'end': 135, 'mesh': 'D004409'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 381, 'end': 391, 'mesh': 'D004409'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 448, 'end': 459, 'mesh': 'D001058'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 539, 'end': 549, 'mesh': 'D004409'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 887, 'end': 897, 'mesh': 'D004409'}]"
+681,9952311,Structural and functional impairment of mitochondria in adriamycin-induced cardiomyopathy in mice: suppression of cytochrome c oxidase II gene expression.,"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.","[{'text': 'Structural and functional impairment of mitochondria', 'type': 'Disease', 'start': 0, 'end': 52, 'mesh': 'D028361'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 56, 'end': 66, 'mesh': 'D004317'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 75, 'end': 89, 'mesh': 'D009202'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 166, 'end': 176, 'mesh': 'D004317'}, {'text': 'ADR', 'type': 'Chemical', 'start': 178, 'end': 181, 'mesh': 'D004317'}, {'text': 'cancer', 'type': 'Disease', 'start': 186, 'end': 192, 'mesh': 'D009369'}, {'text': 'cardiovascular toxicity', 'type': 'Disease', 'start': 245, 'end': 268, 'mesh': 'D002318'}, {'text': 'ADR', 'type': 'Chemical', 'start': 296, 'end': 299, 'mesh': 'D004317'}, {'text': 'ADR', 'type': 'Chemical', 'start': 413, 'end': 416, 'mesh': 'D004317'}, {'text': 'ADR', 'type': 'Chemical', 'start': 526, 'end': 529, 'mesh': 'D004317'}, {'text': 'ADR', 'type': 'Chemical', 'start': 1090, 'end': 1093, 'mesh': 'D004317'}, {'text': 'cardiovascular arrhythmias', 'type': 'Disease', 'start': 1101, 'end': 1127, 'mesh': 'D001145'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 1145, 'end': 1156, 'mesh': 'D001919'}, {'text': 'swelling', 'type': 'Disease', 'start': 1332, 'end': 1340, 'mesh': 'D004487'}, {'text': 'ADR', 'type': 'Chemical', 'start': 1612, 'end': 1615, 'mesh': 'D004317'}, {'text': 'ADR', 'type': 'Chemical', 'start': 1799, 'end': 1802, 'mesh': 'D004317'}, {'text': 'mitochondrial structural and functional impairment', 'type': 'Disease', 'start': 1838, 'end': 1888, 'mesh': 'D028361'}]"
+682,9915601,Enhanced bradycardia induced by beta-adrenoceptor antagonists in rats pretreated with isoniazid.,"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.","[{'text': 'bradycardia', 'type': 'Disease', 'start': 9, 'end': 20, 'mesh': 'D001919'}, {'text': 'isoniazid', 'type': 'Chemical', 'start': 86, 'end': 95, 'mesh': 'D007538'}, {'text': 'isoniazid', 'type': 'Chemical', 'start': 111, 'end': 120, 'mesh': 'D007538'}, {'text': 'hypotension', 'type': 'Disease', 'start': 130, 'end': 141, 'mesh': 'D007022'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 201, 'end': 212, 'mesh': 'D013610'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 216, 'end': 227, 'mesh': 'D001919'}, {'text': 'gamma-aminobutyric acid', 'type': 'Chemical', 'start': 287, 'end': 310, 'mesh': 'D005680'}, {'text': 'GABA', 'type': 'Chemical', 'start': 312, 'end': 316, 'mesh': 'D005680'}, {'text': 'isoniazid', 'type': 'Chemical', 'start': 369, 'end': 378, 'mesh': 'D007538'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 382, 'end': 393, 'mesh': 'D001919'}, {'text': 'chloralose', 'type': 'Chemical', 'start': 477, 'end': 487, 'mesh': 'D002698'}, {'text': 'urethane', 'type': 'Chemical', 'start': 488, 'end': 496, 'mesh': 'D014520'}, {'text': 'Isoniazid', 'type': 'Chemical', 'start': 498, 'end': 507, 'mesh': 'D007538'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 532, 'end': 543, 'mesh': 'D001919'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 550, 'end': 561, 'mesh': 'D011433'}, {'text': 'pindolol', 'type': 'Chemical', 'start': 563, 'end': 571, 'mesh': 'D010869'}, {'text': 'labetalol', 'type': 'Chemical', 'start': 573, 'end': 582, 'mesh': 'D007741'}, {'text': 'atenolol', 'type': 'Chemical', 'start': 587, 'end': 595, 'mesh': 'D001262'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 614, 'end': 623, 'mesh': 'D003000'}, {'text': 'hexamethonium', 'type': 'Chemical', 'start': 639, 'end': 652, 'mesh': 'D018738'}, {'text': 'carbachol', 'type': 'Chemical', 'start': 656, 'end': 665, 'mesh': 'D002217'}, {'text': 'methylatropine', 'type': 'Chemical', 'start': 720, 'end': 734, 'mesh': 'C006649'}, {'text': 'isoniazid', 'type': 'Chemical', 'start': 812, 'end': 821, 'mesh': 'D007538'}]"
+683,9758264,Epileptogenic activity of folic acid after drug induces SLE (folic acid and epilepsy),"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.","[{'text': 'folic acid', 'type': 'Chemical', 'start': 26, 'end': 36, 'mesh': 'D005492'}, {'text': 'SLE', 'type': 'Disease', 'start': 56, 'end': 59, 'mesh': 'D008180'}, {'text': 'folic acid', 'type': 'Chemical', 'start': 61, 'end': 71, 'mesh': 'D005492'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 76, 'end': 84, 'mesh': 'D004827'}, {'text': 'folic acid', 'type': 'Chemical', 'start': 120, 'end': 130, 'mesh': 'D005492'}, {'text': 'epileptic', 'type': 'Disease', 'start': 174, 'end': 183, 'mesh': 'D004827'}, {'text': 'birth defects', 'type': 'Disease', 'start': 263, 'end': 276, 'mesh': 'D000014'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 281, 'end': 289, 'mesh': 'D004827'}, {'text': 'epileptic', 'type': 'Disease', 'start': 427, 'end': 436, 'mesh': 'D004827'}, {'text': 'folic acid', 'type': 'Chemical', 'start': 465, 'end': 475, 'mesh': 'D005492'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 543, 'end': 551, 'mesh': 'D004827'}, {'text': 'epileptic', 'type': 'Disease', 'start': 611, 'end': 620, 'mesh': 'D004827'}, {'text': 'seizures', 'type': 'Disease', 'start': 718, 'end': 726, 'mesh': 'D012640'}, {'text': 'epileptic', 'type': 'Disease', 'start': 804, 'end': 813, 'mesh': 'D004827'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 848, 'end': 861, 'mesh': 'D002220'}, {'text': 'folic acid', 'type': 'Chemical', 'start': 868, 'end': 878, 'mesh': 'D005492'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 957, 'end': 975, 'mesh': 'D013226'}, {'text': 'systemic lupus erythematodes', 'type': 'Disease', 'start': 998, 'end': 1026, 'mesh': 'D008180'}, {'text': 'stillbirth', 'type': 'Disease', 'start': 1053, 'end': 1063, 'mesh': 'D050497'}, {'text': 'epileptic', 'type': 'Disease', 'start': 1082, 'end': 1091, 'mesh': 'D004827'}, {'text': 'autoimmune disease', 'type': 'Disease', 'start': 1111, 'end': 1129, 'mesh': 'D001327'}, {'text': 'lupus', 'type': 'Disease', 'start': 1153, 'end': 1158, 'mesh': 'D008180'}, {'text': 'folic acid', 'type': 'Chemical', 'start': 1245, 'end': 1255, 'mesh': 'D005492'}, {'text': 'seizures', 'type': 'Disease', 'start': 1279, 'end': 1287, 'mesh': 'D012640'}, {'text': 'folic acid', 'type': 'Chemical', 'start': 1319, 'end': 1329, 'mesh': 'D005492'}, {'text': 'epileptic', 'type': 'Disease', 'start': 1353, 'end': 1362, 'mesh': 'D004827'}, {'text': 'autoimmune disease', 'type': 'Disease', 'start': 1386, 'end': 1404, 'mesh': 'D001327'}, {'text': 'epileptic seizures', 'type': 'Disease', 'start': 1436, 'end': 1454, 'mesh': 'D004827'}]"
+684,9669632,Effects of cisapride on symptoms and postcibal small-bowel motor function in patients with irritable bowel syndrome.,"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.","[{'text': 'cisapride', 'type': 'Chemical', 'start': 11, 'end': 20, 'mesh': 'D020117'}, {'text': 'irritable bowel syndrome', 'type': 'Disease', 'start': 91, 'end': 115, 'mesh': 'D043183'}, {'text': 'Irritable bowel syndrome', 'type': 'Disease', 'start': 129, 'end': 153, 'mesh': 'D043183'}, {'text': 'abdominal pain', 'type': 'Disease', 'start': 175, 'end': 189, 'mesh': 'D015746'}, {'text': 'disordered gastrointestinal motility', 'type': 'Disease', 'start': 227, 'end': 263, 'mesh': 'D005767'}, {'text': 'cisapride', 'type': 'Chemical', 'start': 347, 'end': 356, 'mesh': 'D020117'}, {'text': 'irritable bowel syndrome', 'type': 'Disease', 'start': 411, 'end': 435, 'mesh': 'D043183'}, {'text': 'IBS', 'type': 'Disease', 'start': 437, 'end': 440, 'mesh': 'D043183'}, {'text': 'IBS', 'type': 'Disease', 'start': 479, 'end': 482, 'mesh': 'D043183'}, {'text': 'constipation', 'type': 'Disease', 'start': 484, 'end': 496, 'mesh': 'D003248'}, {'text': 'diarrhoea', 'type': 'Disease', 'start': 518, 'end': 527, 'mesh': 'D003967'}, {'text': 'cisapride', 'type': 'Chemical', 'start': 631, 'end': 640, 'mesh': 'D020117'}, {'text': 'diarrhoea', 'type': 'Disease', 'start': 708, 'end': 717, 'mesh': 'D003967'}, {'text': 'cisapride', 'type': 'Chemical', 'start': 820, 'end': 829, 'mesh': 'D020117'}, {'text': 'cisapride', 'type': 'Chemical', 'start': 853, 'end': 862, 'mesh': 'D020117'}, {'text': 'diarrhoea', 'type': 'Disease', 'start': 871, 'end': 880, 'mesh': 'D003967'}, {'text': 'cisapride', 'type': 'Chemical', 'start': 985, 'end': 994, 'mesh': 'D020117'}, {'text': 'cisapride', 'type': 'Chemical', 'start': 1132, 'end': 1141, 'mesh': 'D020117'}, {'text': 'cisapride', 'type': 'Chemical', 'start': 1286, 'end': 1295, 'mesh': 'D020117'}, {'text': 'constipation', 'type': 'Disease', 'start': 1462, 'end': 1474, 'mesh': 'D003248'}, {'text': 'IBS', 'type': 'Disease', 'start': 1487, 'end': 1490, 'mesh': 'D043183'}, {'text': 'constipation', 'type': 'Disease', 'start': 1625, 'end': 1637, 'mesh': 'D003248'}, {'text': 'cisapride', 'type': 'Chemical', 'start': 1652, 'end': 1661, 'mesh': 'D020117'}, {'text': 'constipation', 'type': 'Disease', 'start': 1670, 'end': 1682, 'mesh': 'D003248'}, {'text': 'IBS', 'type': 'Disease', 'start': 1695, 'end': 1698, 'mesh': 'D043183'}, {'text': 'cisapride', 'type': 'Chemical', 'start': 1746, 'end': 1755, 'mesh': 'D020117'}, {'text': 'Diarrhoea', 'type': 'Disease', 'start': 1812, 'end': 1821, 'mesh': 'D003967'}, {'text': 'IBS', 'type': 'Disease', 'start': 1834, 'end': 1837, 'mesh': 'D043183'}, {'text': 'pain', 'type': 'Disease', 'start': 1860, 'end': 1864, 'mesh': 'D010146'}, {'text': 'cisapride', 'type': 'Chemical', 'start': 1877, 'end': 1886, 'mesh': 'D020117'}, {'text': 'cisapride', 'type': 'Chemical', 'start': 1934, 'end': 1943, 'mesh': 'D020117'}, {'text': 'Cisapride', 'type': 'Chemical', 'start': 2012, 'end': 2021, 'mesh': 'D020117'}, {'text': 'IBS', 'type': 'Disease', 'start': 2087, 'end': 2090, 'mesh': 'D043183'}]"
+685,9326871,Clarithromycin-induced ventricular tachycardia.,"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.","[{'text': 'Clarithromycin', 'type': 'Chemical', 'start': 0, 'end': 14, 'mesh': 'D017291'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 23, 'end': 46, 'mesh': 'D017180'}, {'text': 'Clarithromycin', 'type': 'Chemical', 'start': 48, 'end': 62, 'mesh': 'D017291'}, {'text': 'macrolide', 'type': 'Chemical', 'start': 83, 'end': 92, 'mesh': 'D018942'}, {'text': 'erythromycin', 'type': 'Chemical', 'start': 152, 'end': 164, 'mesh': 'D004917'}, {'text': 'erythromycin', 'type': 'Chemical', 'start': 262, 'end': 274, 'mesh': 'D004917'}, {'text': 'gastroenteritis', 'type': 'Disease', 'start': 301, 'end': 316, 'mesh': 'D005759'}, {'text': 'macrolides', 'type': 'Chemical', 'start': 431, 'end': 441, 'mesh': 'D018942'}, {'text': 'Cardiotoxicity', 'type': 'Disease', 'start': 467, 'end': 481, 'mesh': 'D066126'}, {'text': 'erythromycin', 'type': 'Chemical', 'start': 554, 'end': 566, 'mesh': 'D004917'}, {'text': 'macrolides', 'type': 'Chemical', 'start': 610, 'end': 620, 'mesh': 'D018942'}, {'text': 'ventricular dysrhythmias', 'type': 'Disease', 'start': 642, 'end': 666, 'mesh': 'D001145'}, {'text': 'clarithromycin', 'type': 'Chemical', 'start': 712, 'end': 726, 'mesh': 'D017291'}, {'text': 'dysrhythmias', 'type': 'Disease', 'start': 732, 'end': 744, 'mesh': 'D001145'}]"
+686,9226773,Persistent nephrogenic diabetes insipidus following lithium therapy.,"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.","[{'text': 'nephrogenic diabetes insipidus', 'type': 'Disease', 'start': 11, 'end': 41, 'mesh': 'D018500'}, {'text': 'lithium', 'type': 'Chemical', 'start': 52, 'end': 59, 'mesh': 'D008094'}, {'text': 'dehydration', 'type': 'Disease', 'start': 137, 'end': 148, 'mesh': 'D003681'}, {'text': 'head injury', 'type': 'Disease', 'start': 161, 'end': 172, 'mesh': 'D006259'}, {'text': 'lithium', 'type': 'Chemical', 'start': 225, 'end': 232, 'mesh': 'D008094'}, {'text': 'nephrogenic diabetes insipidus', 'type': 'Disease', 'start': 241, 'end': 271, 'mesh': 'D018500'}, {'text': 'lithium', 'type': 'Chemical', 'start': 277, 'end': 284, 'mesh': 'D008094'}, {'text': 'polyuric', 'type': 'Disease', 'start': 340, 'end': 348, 'mesh': 'D011141'}, {'text': 'lithium', 'type': 'Chemical', 'start': 370, 'end': 377, 'mesh': 'D008094'}, {'text': 'vasopressin', 'type': 'Chemical', 'start': 461, 'end': 472, 'mesh': 'D014667'}, {'text': 'nephrogenic diabetes insipidus', 'type': 'Disease', 'start': 507, 'end': 537, 'mesh': 'D018500'}, {'text': 'Lithium', 'type': 'Chemical', 'start': 539, 'end': 546, 'mesh': 'D008094'}, {'text': 'nephrogenic diabetes insipidus', 'type': 'Disease', 'start': 555, 'end': 585, 'mesh': 'D018500'}, {'text': 'polyuria', 'type': 'Disease', 'start': 645, 'end': 653, 'mesh': 'D011141'}, {'text': 'lithium', 'type': 'Chemical', 'start': 700, 'end': 707, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 815, 'end': 822, 'mesh': 'D008094'}, {'text': 'nephrogenic diabetes insipidus', 'type': 'Disease', 'start': 831, 'end': 861, 'mesh': 'D018500'}]"
+687,8600333,Late cardiotoxicity after treatment for a malignant bone tumor.,"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.","[{'text': 'cardiotoxicity', 'type': 'Disease', 'start': 5, 'end': 19, 'mesh': 'D066126'}, {'text': 'bone tumor', 'type': 'Disease', 'start': 52, 'end': 62, 'mesh': 'D001859'}, {'text': 'bone tumors', 'type': 'Disease', 'start': 130, 'end': 141, 'mesh': 'D001859'}, {'text': ""Rosen's T5 or T10 protocol"", 'type': 'Chemical', 'start': 172, 'end': 198, 'mesh': 'C053519'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 215, 'end': 226, 'mesh': 'D004317'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 393, 'end': 404, 'mesh': 'D004317'}, {'text': 'cardiac toxicity', 'type': 'Disease', 'start': 658, 'end': 674, 'mesh': 'D066126'}, {'text': 'ventricular arrhythmias', 'type': 'Disease', 'start': 763, 'end': 786, 'mesh': 'D001145'}, {'text': 'ventricular dilation', 'type': 'Disease', 'start': 793, 'end': 813, 'mesh': 'D002311'}, {'text': 'cardiac abnormalities', 'type': 'Disease', 'start': 895, 'end': 916, 'mesh': 'D006331'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1031, 'end': 1042, 'mesh': 'D004317'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1241, 'end': 1252, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1261, 'end': 1275, 'mesh': 'D066126'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1517, 'end': 1531, 'mesh': 'D066126'}]"
+688,8514073,Venous complications of midazolam versus diazepam.,"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.","[{'text': 'Venous complications', 'type': 'Disease', 'start': 0, 'end': 20, 'mesh': 'D014652'}, {'text': 'midazolam', 'type': 'Chemical', 'start': 24, 'end': 33, 'mesh': 'D008874'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 41, 'end': 49, 'mesh': 'D003975'}, {'text': 'venous complications', 'type': 'Disease', 'start': 94, 'end': 114, 'mesh': 'D014652'}, {'text': 'midazolam', 'type': 'Chemical', 'start': 135, 'end': 144, 'mesh': 'D008874'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 155, 'end': 163, 'mesh': 'D003975'}, {'text': 'venous complications', 'type': 'Disease', 'start': 279, 'end': 299, 'mesh': 'D014652'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 331, 'end': 339, 'mesh': 'D003975'}, {'text': 'midazolam', 'type': 'Chemical', 'start': 343, 'end': 352, 'mesh': 'D008874'}, {'text': 'venous complications', 'type': 'Disease', 'start': 445, 'end': 465, 'mesh': 'D014652'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 490, 'end': 498, 'mesh': 'D003975'}, {'text': 'midazolam', 'type': 'Chemical', 'start': 529, 'end': 538, 'mesh': 'D008874'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 643, 'end': 651, 'mesh': 'D003975'}, {'text': 'midazolam', 'type': 'Chemical', 'start': 702, 'end': 711, 'mesh': 'D008874'}, {'text': 'Pain', 'type': 'Disease', 'start': 731, 'end': 735, 'mesh': 'D010146'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 804, 'end': 812, 'mesh': 'D003975'}, {'text': 'midazolam', 'type': 'Chemical', 'start': 862, 'end': 871, 'mesh': 'D008874'}, {'text': 'Swelling', 'type': 'Disease', 'start': 891, 'end': 899, 'mesh': 'D004487'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 1093, 'end': 1100, 'mesh': 'D000431'}, {'text': 'pain', 'type': 'Disease', 'start': 1110, 'end': 1114, 'mesh': 'D010146'}, {'text': 'venous complications', 'type': 'Disease', 'start': 1170, 'end': 1190, 'mesh': 'D014652'}]"
+689,8492347,Tetany and rhabdomyolysis due to surreptitious furosemide--importance of magnesium supplementation.,"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.","[{'text': 'Tetany', 'type': 'Disease', 'start': 0, 'end': 6, 'mesh': 'D013746'}, {'text': 'rhabdomyolysis', 'type': 'Disease', 'start': 11, 'end': 25, 'mesh': 'D012206'}, {'text': 'furosemide', 'type': 'Chemical', 'start': 47, 'end': 57, 'mesh': 'D005665'}, {'text': 'magnesium', 'type': 'Chemical', 'start': 73, 'end': 82, 'mesh': 'D008274'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 121, 'end': 132, 'mesh': 'D007008'}, {'text': 'hypocalcemia', 'type': 'Disease', 'start': 134, 'end': 146, 'mesh': 'D006996'}, {'text': 'hypomagnesemia', 'type': 'Disease', 'start': 151, 'end': 165, 'mesh': 'C537153'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 180, 'end': 191, 'mesh': 'D007008'}, {'text': 'muscle weakness', 'type': 'Disease', 'start': 202, 'end': 217, 'mesh': 'D018908'}, {'text': 'hypomagnesemia', 'type': 'Disease', 'start': 226, 'end': 240, 'mesh': 'C537153'}, {'text': 'muscle spasms', 'type': 'Disease', 'start': 260, 'end': 273, 'mesh': 'D013035'}, {'text': 'tetany', 'type': 'Disease', 'start': 278, 'end': 284, 'mesh': 'D013746'}, {'text': 'potassium', 'type': 'Chemical', 'start': 314, 'end': 323, 'mesh': 'D011188'}, {'text': 'calcium', 'type': 'Chemical', 'start': 328, 'end': 335, 'mesh': 'D002118'}, {'text': 'obese', 'type': 'Disease', 'start': 466, 'end': 471, 'mesh': 'D009765'}, {'text': 'edematous', 'type': 'Disease', 'start': 475, 'end': 484, 'mesh': 'D004487'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 498, 'end': 509, 'mesh': 'D007008'}, {'text': 'hypocalcemia', 'type': 'Disease', 'start': 567, 'end': 579, 'mesh': 'D006996'}, {'text': 'magnesium', 'type': 'Chemical', 'start': 617, 'end': 626, 'mesh': 'D008274'}]"
+690,8410199,Loss of glutamate decarboxylase mRNA-containing neurons in the rat dentate gyrus following pilocarpine-induced seizures.,"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.","[{'text': 'glutamate', 'type': 'Chemical', 'start': 8, 'end': 17, 'mesh': 'D018698'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 91, 'end': 102, 'mesh': 'D010862'}, {'text': 'seizures', 'type': 'Disease', 'start': 111, 'end': 119, 'mesh': 'D012640'}, {'text': 'glutamic acid', 'type': 'Chemical', 'start': 177, 'end': 190, 'mesh': 'D018698'}, {'text': 'seizure', 'type': 'Disease', 'start': 291, 'end': 298, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 336, 'end': 344, 'mesh': 'D012640'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 403, 'end': 414, 'mesh': 'D010862'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 512, 'end': 523, 'mesh': 'D010862'}, {'text': 'seizures', 'type': 'Disease', 'start': 532, 'end': 540, 'mesh': 'D012640'}, {'text': 'digoxigenin', 'type': 'Chemical', 'start': 588, 'end': 599, 'mesh': 'D004076'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 746, 'end': 757, 'mesh': 'D010862'}, {'text': 'cresyl violet', 'type': 'Chemical', 'start': 865, 'end': 878, 'mesh': 'C028911'}, {'text': 'neuronal degeneration', 'type': 'Disease', 'start': 889, 'end': 910, 'mesh': 'D009410'}, {'text': 'neuronal loss', 'type': 'Disease', 'start': 1075, 'end': 1088, 'mesh': 'D009410'}, {'text': 'seizure', 'type': 'Disease', 'start': 1877, 'end': 1884, 'mesh': 'D012640'}, {'text': 'GABA', 'type': 'Chemical', 'start': 1990, 'end': 1994, 'mesh': 'D005680'}]"
+691,7791169,Protective effect of misoprostol on indomethacin induced renal dysfunction in elderly patients.,"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.","[{'text': 'misoprostol', 'type': 'Chemical', 'start': 21, 'end': 32, 'mesh': 'D016595'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 36, 'end': 48, 'mesh': 'D007213'}, {'text': 'renal dysfunction', 'type': 'Disease', 'start': 57, 'end': 74, 'mesh': 'D007674'}, {'text': 'misoprostol', 'type': 'Chemical', 'start': 154, 'end': 165, 'mesh': 'D016595'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 230, 'end': 242, 'mesh': 'D007213'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 422, 'end': 434, 'mesh': 'D007213'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 461, 'end': 473, 'mesh': 'D007213'}, {'text': 'misoprostol', 'type': 'Chemical', 'start': 490, 'end': 501, 'mesh': 'D016595'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 573, 'end': 583, 'mesh': 'D003404'}, {'text': 'blood urea nitrogen', 'type': 'Chemical', 'start': 585, 'end': 604, 'mesh': 'D001806'}, {'text': 'BUN', 'type': 'Chemical', 'start': 606, 'end': 609, 'mesh': 'D001806'}, {'text': 'pain', 'type': 'Disease', 'start': 832, 'end': 836, 'mesh': 'D010146'}, {'text': 'BUN', 'type': 'Chemical', 'start': 920, 'end': 923, 'mesh': 'D001806'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 928, 'end': 938, 'mesh': 'D003404'}, {'text': 'Potassium', 'type': 'Chemical', 'start': 1086, 'end': 1095, 'mesh': 'D011188'}, {'text': 'K', 'type': 'Chemical', 'start': 1097, 'end': 1098, 'mesh': 'D011188'}, {'text': 'BUN', 'type': 'Chemical', 'start': 1234, 'end': 1237, 'mesh': 'D001806'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1239, 'end': 1249, 'mesh': 'D003404'}, {'text': 'K', 'type': 'Chemical', 'start': 1255, 'end': 1256, 'mesh': 'D011188'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 1487, 'end': 1499, 'mesh': 'D007213'}, {'text': 'renal dysfunction', 'type': 'Disease', 'start': 1508, 'end': 1525, 'mesh': 'D007674'}, {'text': 'misoprostol', 'type': 'Chemical', 'start': 1539, 'end': 1550, 'mesh': 'D016595'}, {'text': 'renal impairment', 'type': 'Disease', 'start': 1569, 'end': 1585, 'mesh': 'D007674'}, {'text': 'pain', 'type': 'Disease', 'start': 1604, 'end': 1608, 'mesh': 'D010146'}]"
+692,6728084,Nephrotoxic effects of aminoglycoside treatment on renal protein reabsorption and accumulation.,"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.","[{'text': 'Nephrotoxic', 'type': 'Disease', 'start': 0, 'end': 11, 'mesh': 'D007674'}, {'text': 'aminoglycoside', 'type': 'Chemical', 'start': 23, 'end': 37, 'mesh': 'D000617'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 123, 'end': 133, 'mesh': 'D005839'}, {'text': 'kanamycin', 'type': 'Chemical', 'start': 135, 'end': 144, 'mesh': 'D007612'}, {'text': 'netilmicin', 'type': 'Chemical', 'start': 149, 'end': 159, 'mesh': 'D009428'}, {'text': 'sodium', 'type': 'Chemical', 'start': 384, 'end': 390, 'mesh': 'D012964'}, {'text': 'potassium', 'type': 'Chemical', 'start': 392, 'end': 401, 'mesh': 'D011188'}, {'text': 'Gentamicin', 'type': 'Chemical', 'start': 638, 'end': 648, 'mesh': 'D005839'}, {'text': 'Kanamycin', 'type': 'Chemical', 'start': 728, 'end': 737, 'mesh': 'D007612'}, {'text': 'netilmicin', 'type': 'Chemical', 'start': 742, 'end': 752, 'mesh': 'D009428'}, {'text': 'aminoglycosides', 'type': 'Chemical', 'start': 808, 'end': 823, 'mesh': 'D000617'}, {'text': 'sodium', 'type': 'Chemical', 'start': 873, 'end': 879, 'mesh': 'D012964'}, {'text': 'potassium', 'type': 'Chemical', 'start': 884, 'end': 893, 'mesh': 'D011188'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 901, 'end': 911, 'mesh': 'D005839'}, {'text': 'kanamycin', 'type': 'Chemical', 'start': 916, 'end': 925, 'mesh': 'D007612'}, {'text': 'netilmicin', 'type': 'Chemical', 'start': 1041, 'end': 1051, 'mesh': 'D009428'}, {'text': 'kanamycin', 'type': 'Chemical', 'start': 1165, 'end': 1174, 'mesh': 'D007612'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 1179, 'end': 1189, 'mesh': 'D005839'}, {'text': 'aminoglycosides', 'type': 'Chemical', 'start': 1197, 'end': 1212, 'mesh': 'D000617'}, {'text': 'impairment of renal reabsorption', 'type': 'Disease', 'start': 1284, 'end': 1316, 'mesh': 'D007674'}]"
+693,6111982,"Pharmacology of GYKI-41 099 (chlorpropanol, Tobanum) a new potent beta-adrenergic antagonist.","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.","[{'text': 'GYKI-41 099', 'type': 'Chemical', 'start': 16, 'end': 27, 'mesh': 'C025725'}, {'text': 'chlorpropanol', 'type': 'Chemical', 'start': 29, 'end': 42, 'mesh': 'C025725'}, {'text': 'Tobanum', 'type': 'Chemical', 'start': 44, 'end': 51, 'mesh': 'C025725'}, {'text': 'GYKI-41 099', 'type': 'Chemical', 'start': 107, 'end': 118, 'mesh': 'C025725'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 183, 'end': 194, 'mesh': 'D011433'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 268, 'end': 279, 'mesh': 'D011433'}, {'text': 'pindolol', 'type': 'Chemical', 'start': 284, 'end': 292, 'mesh': 'D010869'}, {'text': 'ouabain', 'type': 'Chemical', 'start': 308, 'end': 315, 'mesh': 'D010042'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 316, 'end': 326, 'mesh': 'D001145'}, {'text': 'GYKI-41 900', 'type': 'Chemical', 'start': 345, 'end': 356, 'mesh': '-1'}, {'text': '14C-41 099', 'type': 'Chemical', 'start': 558, 'end': 568, 'mesh': '-1'}]"
+694,3123611,Chorea associated with oral contraception.,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.,"[{'text': 'Chorea', 'type': 'Disease', 'start': 0, 'end': 6, 'mesh': 'D002819'}, {'text': 'oral contraception', 'type': 'Chemical', 'start': 23, 'end': 41, 'mesh': 'D003276'}, {'text': 'chorea', 'type': 'Disease', 'start': 68, 'end': 74, 'mesh': 'D002819'}, {'text': 'oral contraceptives', 'type': 'Chemical', 'start': 91, 'end': 110, 'mesh': 'D003276'}, {'text': 'chorea', 'type': 'Disease', 'start': 142, 'end': 148, 'mesh': 'D002819'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 278, 'end': 289, 'mesh': 'D000661'}, {'text': 'chorea', 'type': 'Disease', 'start': 298, 'end': 304, 'mesh': 'D002819'}, {'text': 'oral contraception', 'type': 'Chemical', 'start': 321, 'end': 339, 'mesh': 'D003276'}, {'text': 'chorea', 'type': 'Disease', 'start': 412, 'end': 418, 'mesh': 'D002819'}, {'text': 'chorea', 'type': 'Disease', 'start': 456, 'end': 462, 'mesh': 'D002819'}, {'text': 'rheumatic fever', 'type': 'Disease', 'start': 466, 'end': 481, 'mesh': 'D012213'}]"
+695,761833,Reversal of ammonia coma in rats by L-dopa: a peripheral effect.,"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.","[{'text': 'ammonia', 'type': 'Chemical', 'start': 12, 'end': 19, 'mesh': 'D000641'}, {'text': 'coma', 'type': 'Disease', 'start': 20, 'end': 24, 'mesh': 'D003128'}, {'text': 'L-dopa', 'type': 'Chemical', 'start': 36, 'end': 42, 'mesh': 'D007980'}, {'text': 'Ammonia', 'type': 'Chemical', 'start': 65, 'end': 72, 'mesh': 'D000641'}, {'text': 'coma', 'type': 'Disease', 'start': 73, 'end': 77, 'mesh': 'D003128'}, {'text': 'NH4CL', 'type': 'Chemical', 'start': 166, 'end': 171, 'mesh': 'D000643'}, {'text': 'coma', 'type': 'Disease', 'start': 178, 'end': 182, 'mesh': 'D003128'}, {'text': 'L-dopa', 'type': 'Chemical', 'start': 212, 'end': 218, 'mesh': 'D007980'}, {'text': 'ammonium salt', 'type': 'Chemical', 'start': 269, 'end': 282, 'mesh': 'D064751'}, {'text': 'L-dopa', 'type': 'Chemical', 'start': 308, 'end': 314, 'mesh': 'D007980'}, {'text': 'ammonia', 'type': 'Chemical', 'start': 365, 'end': 372, 'mesh': 'D000641'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 395, 'end': 403, 'mesh': 'D004298'}, {'text': 'ammonia', 'type': 'Chemical', 'start': 443, 'end': 450, 'mesh': 'D000641'}, {'text': 'urea', 'type': 'Chemical', 'start': 455, 'end': 459, 'mesh': 'D014508'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 490, 'end': 498, 'mesh': 'D004298'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 529, 'end': 537, 'mesh': 'D004298'}, {'text': 'ammonia', 'type': 'Chemical', 'start': 577, 'end': 584, 'mesh': 'D000641'}, {'text': 'coma', 'type': 'Disease', 'start': 585, 'end': 589, 'mesh': 'D003128'}, {'text': 'ammonia', 'type': 'Chemical', 'start': 621, 'end': 628, 'mesh': 'D000641'}, {'text': 'L-dopa', 'type': 'Chemical', 'start': 703, 'end': 709, 'mesh': 'D007980'}, {'text': 'ammonia', 'type': 'Chemical', 'start': 729, 'end': 736, 'mesh': 'D000641'}, {'text': 'ammonia', 'type': 'Chemical', 'start': 745, 'end': 752, 'mesh': 'D000641'}, {'text': 'coma', 'type': 'Disease', 'start': 753, 'end': 757, 'mesh': 'D003128'}, {'text': 'ammonia', 'type': 'Chemical', 'start': 816, 'end': 823, 'mesh': 'D000641'}, {'text': 'ammonia', 'type': 'Chemical', 'start': 846, 'end': 853, 'mesh': 'D000641'}, {'text': 'coma', 'type': 'Disease', 'start': 854, 'end': 858, 'mesh': 'D003128'}, {'text': 'L-dopa', 'type': 'Chemical', 'start': 865, 'end': 871, 'mesh': 'D007980'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 922, 'end': 930, 'mesh': 'D004298'}, {'text': 'encephalopathic', 'type': 'Disease', 'start': 1072, 'end': 1087, 'mesh': 'D001927'}, {'text': 'L-dopa', 'type': 'Chemical', 'start': 1107, 'end': 1113, 'mesh': 'D007980'}]"
+696,18589141,Heparin-induced thrombocytopenia after liver transplantation.,"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.","[{'text': 'Heparin', 'type': 'Chemical', 'start': 0, 'end': 7, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 16, 'end': 32, 'mesh': 'D013921'}, {'text': 'Unfractionated heparin sodium', 'type': 'Chemical', 'start': 74, 'end': 103, 'mesh': 'D006493'}, {'text': 'UFH', 'type': 'Chemical', 'start': 105, 'end': 108, 'mesh': 'D006493'}, {'text': 'low-molecular weight heparin', 'type': 'Chemical', 'start': 113, 'end': 141, 'mesh': 'D006495'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 219, 'end': 229, 'mesh': 'D013927'}, {'text': 'Heparin', 'type': 'Chemical', 'start': 259, 'end': 266, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 275, 'end': 291, 'mesh': 'D013921'}, {'text': 'HIT', 'type': 'Disease', 'start': 293, 'end': 296, 'mesh': 'D013921'}, {'text': 'heparin', 'type': 'Chemical', 'start': 340, 'end': 347, 'mesh': 'D006493'}, {'text': 'HIT', 'type': 'Disease', 'start': 424, 'end': 427, 'mesh': 'D013921'}, {'text': 'heparin', 'type': 'Chemical', 'start': 478, 'end': 485, 'mesh': 'D006493'}, {'text': 'HIT', 'type': 'Disease', 'start': 505, 'end': 508, 'mesh': 'D013921'}, {'text': 'UFH', 'type': 'Chemical', 'start': 751, 'end': 754, 'mesh': 'D006493'}, {'text': 'UFH', 'type': 'Chemical', 'start': 793, 'end': 796, 'mesh': 'D006493'}, {'text': 'HIT', 'type': 'Disease', 'start': 857, 'end': 860, 'mesh': 'D013921'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 1149, 'end': 1159, 'mesh': 'D013927'}, {'text': 'HIT', 'type': 'Disease', 'start': 1211, 'end': 1214, 'mesh': 'D013921'}, {'text': 'heparin', 'type': 'Chemical', 'start': 1459, 'end': 1466, 'mesh': 'D006493'}, {'text': 'platelet aggregation', 'type': 'Disease', 'start': 1475, 'end': 1495, 'mesh': 'D001791'}, {'text': 'HIT', 'type': 'Disease', 'start': 1551, 'end': 1554, 'mesh': 'D013921'}, {'text': 'UFH', 'type': 'Chemical', 'start': 1682, 'end': 1685, 'mesh': 'D006493'}, {'text': 'HIT', 'type': 'Disease', 'start': 1694, 'end': 1697, 'mesh': 'D013921'}, {'text': 'HIT', 'type': 'Disease', 'start': 1745, 'end': 1748, 'mesh': 'D013921'}]"
+697,16418614,PTU-associated vasculitis in a girl with Turner Syndrome and Graves' disease.,"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.","[{'text': 'PTU', 'type': 'Chemical', 'start': 0, 'end': 3, 'mesh': 'D011441'}, {'text': 'vasculitis', 'type': 'Disease', 'start': 15, 'end': 25, 'mesh': 'D014657'}, {'text': 'Turner Syndrome', 'type': 'Disease', 'start': 41, 'end': 56, 'mesh': 'D014424'}, {'text': ""Graves' disease"", 'type': 'Disease', 'start': 61, 'end': 76, 'mesh': 'D006111'}, {'text': 'purpura', 'type': 'Disease', 'start': 87, 'end': 94, 'mesh': 'D011693'}, {'text': 'vasculitis', 'type': 'Disease', 'start': 250, 'end': 260, 'mesh': 'D014657'}, {'text': 'Turner syndrome', 'type': 'Disease', 'start': 393, 'end': 408, 'mesh': 'D014424'}, {'text': ""Graves' disease"", 'type': 'Disease', 'start': 413, 'end': 428, 'mesh': 'D006111'}, {'text': 'purpuric lesions', 'type': 'Disease', 'start': 457, 'end': 473, 'mesh': 'D011693'}, {'text': 'propylthiouracil', 'type': 'Chemical', 'start': 492, 'end': 508, 'mesh': 'D011441'}, {'text': 'PTU', 'type': 'Chemical', 'start': 510, 'end': 513, 'mesh': 'D011441'}, {'text': 'vasculitis', 'type': 'Disease', 'start': 526, 'end': 536, 'mesh': 'D014657'}, {'text': 'PTU', 'type': 'Chemical', 'start': 720, 'end': 723, 'mesh': 'D011441'}, {'text': 'hyperthyroidism', 'type': 'Disease', 'start': 760, 'end': 775, 'mesh': 'D006980'}, {'text': 'vasculitis', 'type': 'Disease', 'start': 836, 'end': 846, 'mesh': 'D014657'}]"
+698,15893386,Succinylcholine-induced masseter muscle rigidity during bronchoscopic removal of a tracheal foreign body.,"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.","[{'text': 'Succinylcholine', 'type': 'Chemical', 'start': 0, 'end': 15, 'mesh': 'D013390'}, {'text': 'masseter muscle rigidity', 'type': 'Disease', 'start': 24, 'end': 48, 'mesh': 'D014313'}, {'text': 'Masseter muscle rigidity', 'type': 'Disease', 'start': 106, 'end': 130, 'mesh': 'D014313'}, {'text': 'malignant hyperthermia', 'type': 'Disease', 'start': 218, 'end': 240, 'mesh': 'D008305'}, {'text': 'masseter muscle rigidity', 'type': 'Disease', 'start': 358, 'end': 382, 'mesh': 'D014313'}, {'text': 'masseter muscle rigidity', 'type': 'Disease', 'start': 419, 'end': 443, 'mesh': 'D014313'}, {'text': 'jaw of steel', 'type': 'Disease', 'start': 445, 'end': 457, 'mesh': 'D014313'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 465, 'end': 480, 'mesh': 'D013390'}, {'text': 'Sch', 'type': 'Chemical', 'start': 482, 'end': 485, 'mesh': 'D013390'}, {'text': 'propofol', 'type': 'Chemical', 'start': 642, 'end': 650, 'mesh': 'D015742'}, {'text': 'malignant hyperthermia', 'type': 'Disease', 'start': 716, 'end': 738, 'mesh': 'D008305'}]"
+699,15814210,"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.","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.","[{'text': 'neurological dysfunction', 'type': 'Disease', 'start': 6, 'end': 30, 'mesh': 'D009422'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 112, 'end': 125, 'mesh': 'D003907'}, {'text': 'neurological dysfunction', 'type': 'Disease', 'start': 218, 'end': 242, 'mesh': 'D009422'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 297, 'end': 310, 'mesh': 'D003907'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 380, 'end': 393, 'mesh': 'D003907'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 440, 'end': 453, 'mesh': 'D003907'}, {'text': 'Dexamethasone', 'type': 'Chemical', 'start': 509, 'end': 522, 'mesh': 'D003907'}, {'text': 'asphyxia', 'type': 'Disease', 'start': 649, 'end': 657, 'mesh': 'D001237'}, {'text': 'malformations', 'type': 'Disease', 'start': 659, 'end': 672, 'mesh': 'D000014'}, {'text': 'haemorrhage', 'type': 'Disease', 'start': 748, 'end': 759, 'mesh': 'D006470'}, {'text': 'periventricular leukomalacia', 'type': 'Disease', 'start': 779, 'end': 807, 'mesh': 'D007969'}, {'text': 'psychomotor retardation', 'type': 'Disease', 'start': 820, 'end': 843, 'mesh': 'D011596'}, {'text': 'neurological dysfunctions', 'type': 'Disease', 'start': 902, 'end': 927, 'mesh': 'D009422'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 1460, 'end': 1473, 'mesh': 'D003907'}, {'text': 'neurological dysfunctions', 'type': 'Disease', 'start': 1524, 'end': 1549, 'mesh': 'D009422'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 1712, 'end': 1725, 'mesh': 'D003907'}]"
+700,11912119,Force overflow and levodopa-induced dyskinesias in Parkinson's disease.,"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.","[{'text': 'levodopa', 'type': 'Chemical', 'start': 19, 'end': 27, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 36, 'end': 47, 'mesh': 'D004409'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 51, 'end': 70, 'mesh': 'D010300'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 118, 'end': 137, 'mesh': 'D010300'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 185, 'end': 193, 'mesh': 'D007980'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 219, 'end': 227, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 236, 'end': 247, 'mesh': 'D004409'}, {'text': 'LID', 'type': 'Disease', 'start': 249, 'end': 252, 'mesh': 'D004409'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 280, 'end': 299, 'mesh': 'D010300'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 315, 'end': 334, 'mesh': 'D010300'}, {'text': 'LID', 'type': 'Disease', 'start': 337, 'end': 340, 'mesh': 'D004409'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 362, 'end': 370, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 379, 'end': 390, 'mesh': 'D004409'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 392, 'end': 411, 'mesh': 'D010300'}, {'text': 'LID', 'type': 'Disease', 'start': 414, 'end': 417, 'mesh': 'D004409'}, {'text': ""Parkinson's Disease"", 'type': 'Disease', 'start': 493, 'end': 512, 'mesh': 'D010300'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 529, 'end': 539, 'mesh': 'D004409'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 605, 'end': 613, 'mesh': 'D007980'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 673, 'end': 692, 'mesh': 'D010300'}, {'text': 'LID', 'type': 'Disease', 'start': 695, 'end': 698, 'mesh': 'D004409'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 708, 'end': 727, 'mesh': 'D010300'}, {'text': 'LID', 'type': 'Disease', 'start': 730, 'end': 733, 'mesh': 'D004409'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 828, 'end': 836, 'mesh': 'D007980'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 1060, 'end': 1079, 'mesh': 'D010300'}, {'text': 'LID', 'type': 'Disease', 'start': 1082, 'end': 1085, 'mesh': 'D004409'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 1145, 'end': 1164, 'mesh': 'D010300'}, {'text': 'LID', 'type': 'Disease', 'start': 1167, 'end': 1170, 'mesh': 'D004409'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 1179, 'end': 1198, 'mesh': 'D010300'}, {'text': 'LID', 'type': 'Disease', 'start': 1201, 'end': 1204, 'mesh': 'D004409'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 1301, 'end': 1312, 'mesh': 'D004409'}, {'text': 'LID', 'type': 'Disease', 'start': 1573, 'end': 1576, 'mesh': 'D004409'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 1670, 'end': 1681, 'mesh': 'D004409'}, {'text': 'LID', 'type': 'Disease', 'start': 1731, 'end': 1734, 'mesh': 'D004409'}]"
+701,9105126,Postinfarction ventricular septal defect associated with long-term steroid therapy.,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.,"[{'text': 'ventricular septal defect', 'type': 'Disease', 'start': 15, 'end': 40, 'mesh': 'D018658'}, {'text': 'steroid', 'type': 'Chemical', 'start': 67, 'end': 74, 'mesh': 'D013256'}, {'text': 'ventricular septal rupture', 'type': 'Disease', 'start': 112, 'end': 138, 'mesh': 'D018658'}, {'text': 'steroid', 'type': 'Chemical', 'start': 164, 'end': 171, 'mesh': 'D013256'}, {'text': 'steroid', 'type': 'Chemical', 'start': 277, 'end': 284, 'mesh': 'D013256'}, {'text': 'septal rupture', 'type': 'Disease', 'start': 323, 'end': 337, 'mesh': 'D018658'}]"
+702,8599504,Angioedema associated with droperidol administration.,"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.","[{'text': 'Angioedema', 'type': 'Disease', 'start': 0, 'end': 10, 'mesh': 'D000799'}, {'text': 'droperidol', 'type': 'Chemical', 'start': 27, 'end': 37, 'mesh': 'D004329'}, {'text': 'Angioedema', 'type': 'Disease', 'start': 54, 'end': 64, 'mesh': 'D000799'}, {'text': 'angioneurotic edema', 'type': 'Disease', 'start': 80, 'end': 99, 'mesh': 'D000799'}, {'text': ""Quincke's disease"", 'type': 'Disease', 'start': 103, 'end': 120, 'mesh': 'D000799'}, {'text': 'edema', 'type': 'Disease', 'start': 154, 'end': 159, 'mesh': 'D004487'}, {'text': 'upper-airway obstruction', 'type': 'Disease', 'start': 210, 'end': 234, 'mesh': 'D000402'}, {'text': 'drug allergies', 'type': 'Disease', 'start': 309, 'end': 323, 'mesh': 'D004342'}, {'text': 'angioedema', 'type': 'Disease', 'start': 332, 'end': 342, 'mesh': 'D000799'}, {'text': 'droperidol', 'type': 'Chemical', 'start': 464, 'end': 474, 'mesh': 'D004329'}]"
+703,8546130,Clarithromycin-associated visual hallucinations in a patient with chronic renal failure on continuous ambulatory peritoneal dialysis.,"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.","[{'text': 'Clarithromycin', 'type': 'Chemical', 'start': 0, 'end': 14, 'mesh': 'D017291'}, {'text': 'visual hallucinations', 'type': 'Disease', 'start': 26, 'end': 47, 'mesh': 'D006212'}, {'text': 'chronic renal failure', 'type': 'Disease', 'start': 66, 'end': 87, 'mesh': 'D007676'}, {'text': 'Visual hallucinations', 'type': 'Disease', 'start': 134, 'end': 155, 'mesh': 'D006212'}, {'text': 'chronic renal failure', 'type': 'Disease', 'start': 176, 'end': 197, 'mesh': 'D007676'}, {'text': 'uremia', 'type': 'Disease', 'start': 217, 'end': 223, 'mesh': 'D014511'}, {'text': 'visual hallucinations', 'type': 'Disease', 'start': 264, 'end': 285, 'mesh': 'D006212'}, {'text': 'macrolide', 'type': 'Chemical', 'start': 324, 'end': 333, 'mesh': 'D018942'}, {'text': 'clarithromycin', 'type': 'Chemical', 'start': 346, 'end': 360, 'mesh': 'D017291'}, {'text': 'end-stage renal disease', 'type': 'Disease', 'start': 404, 'end': 427, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 429, 'end': 433, 'mesh': 'D007676'}, {'text': 'clarithromycin', 'type': 'Chemical', 'start': 544, 'end': 558, 'mesh': 'D017291'}, {'text': 'chronic renal failure', 'type': 'Disease', 'start': 570, 'end': 591, 'mesh': 'D007676'}, {'text': 'aluminum', 'type': 'Chemical', 'start': 644, 'end': 652, 'mesh': 'D000535'}, {'text': 'neurotoxic', 'type': 'Disease', 'start': 711, 'end': 721, 'mesh': 'D020258'}, {'text': 'chronic renal failure', 'type': 'Disease', 'start': 812, 'end': 833, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 939, 'end': 943, 'mesh': 'D007676'}]"
+704,7724492,Acute renal toxicity of doxorubicin (adriamycin)-loaded cyanoacrylate nanoparticles.,"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.","[{'text': 'renal toxicity', 'type': 'Disease', 'start': 6, 'end': 20, 'mesh': 'D007674'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 24, 'end': 35, 'mesh': 'D004317'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 37, 'end': 47, 'mesh': 'D004317'}, {'text': 'cyanoacrylate', 'type': 'Chemical', 'start': 56, 'end': 69, 'mesh': 'D003487'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 91, 'end': 102, 'mesh': 'D004317'}, {'text': 'renal toxicity', 'type': 'Disease', 'start': 130, 'end': 144, 'mesh': 'D007674'}, {'text': 'glomerulonephritis', 'type': 'Disease', 'start': 205, 'end': 223, 'mesh': 'D005921'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 261, 'end': 272, 'mesh': 'D004317'}, {'text': 'DX', 'type': 'Chemical', 'start': 274, 'end': 276, 'mesh': 'D004317'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 410, 'end': 421, 'mesh': 'D011507'}, {'text': 'DX', 'type': 'Chemical', 'start': 487, 'end': 489, 'mesh': 'D004317'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 519, 'end': 530, 'mesh': 'D011507'}, {'text': 'DX', 'type': 'Chemical', 'start': 613, 'end': 615, 'mesh': 'D004317'}, {'text': 'glomerulonephritis', 'type': 'Disease', 'start': 662, 'end': 680, 'mesh': 'D005921'}, {'text': 'DX', 'type': 'Chemical', 'start': 697, 'end': 699, 'mesh': 'D004317'}, {'text': 'Proteinuria', 'type': 'Disease', 'start': 798, 'end': 809, 'mesh': 'D011507'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 897, 'end': 908, 'mesh': 'D004317'}, {'text': 'DX', 'type': 'Chemical', 'start': 985, 'end': 987, 'mesh': 'D004317'}, {'text': 'DX', 'type': 'Chemical', 'start': 1139, 'end': 1141, 'mesh': 'D004317'}, {'text': 'renal toxicity', 'type': 'Disease', 'start': 1166, 'end': 1180, 'mesh': 'D007674'}, {'text': 'nephrosis', 'type': 'Disease', 'start': 1230, 'end': 1239, 'mesh': 'D009401'}]"
+705,7619765,Etoposide-related myocardial infarction.,"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.","[{'text': 'Etoposide', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D005047'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 18, 'end': 39, 'mesh': 'D009203'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 61, 'end': 82, 'mesh': 'D009203'}, {'text': 'etoposide', 'type': 'Chemical', 'start': 125, 'end': 134, 'mesh': 'D005047'}, {'text': 'coronary heart disease', 'type': 'Disease', 'start': 170, 'end': 192, 'mesh': 'D003327'}]"
+706,7416947,Subjective assessment of sexual dysfunction of patients on long-term administration of digoxin.,"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.","[{'text': 'sexual dysfunction', 'type': 'Disease', 'start': 25, 'end': 43, 'mesh': 'D020018'}, {'text': 'digoxin', 'type': 'Chemical', 'start': 87, 'end': 94, 'mesh': 'D004077'}, {'text': 'digoxin', 'type': 'Chemical', 'start': 154, 'end': 161, 'mesh': 'D004077'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 213, 'end': 221, 'mesh': 'D004967'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 253, 'end': 265, 'mesh': 'D013739'}, {'text': 'digoxin', 'type': 'Chemical', 'start': 387, 'end': 394, 'mesh': 'D004077'}, {'text': 'digoxin', 'type': 'Chemical', 'start': 442, 'end': 449, 'mesh': 'D004077'}, {'text': 'estradiol', 'type': 'Chemical', 'start': 470, 'end': 479, 'mesh': 'D004958'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 481, 'end': 493, 'mesh': 'D013739'}, {'text': 'digoxin', 'type': 'Chemical', 'start': 556, 'end': 563, 'mesh': 'D004077'}, {'text': 'rheumatic heart disease', 'type': 'Disease', 'start': 667, 'end': 690, 'mesh': 'D012214'}, {'text': 'digoxin', 'type': 'Chemical', 'start': 1025, 'end': 1032, 'mesh': 'D004077'}, {'text': 'estradiol', 'type': 'Chemical', 'start': 1050, 'end': 1059, 'mesh': 'D004958'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 1061, 'end': 1073, 'mesh': 'D013739'}, {'text': 'decrease in sexual desire', 'type': 'Disease', 'start': 1205, 'end': 1230, 'mesh': 'D020018'}]"
+707,7263204,Fatal aplastic anemia due to indomethacin--lymphocyte transformation tests in vitro.,"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.","[{'text': 'aplastic anemia', 'type': 'Disease', 'start': 6, 'end': 21, 'mesh': 'D000741'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 29, 'end': 41, 'mesh': 'D007213'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 94, 'end': 106, 'mesh': 'D007213'}, {'text': 'aplastic anemia', 'type': 'Disease', 'start': 150, 'end': 165, 'mesh': 'D000741'}, {'text': 'aplastic anemia', 'type': 'Disease', 'start': 273, 'end': 288, 'mesh': 'D000741'}, {'text': 'allopurinol', 'type': 'Chemical', 'start': 331, 'end': 342, 'mesh': 'D000493'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 347, 'end': 359, 'mesh': 'D007213'}, {'text': 'Indomethacin', 'type': 'Chemical', 'start': 372, 'end': 384, 'mesh': 'D007213'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 491, 'end': 503, 'mesh': 'D007213'}, {'text': 'aplastic anemia', 'type': 'Disease', 'start': 578, 'end': 593, 'mesh': 'D000741'}]"
+708,7066357,Plasma and urinary lipids and lipoproteins during the development of nephrotic syndrome induced in the rat by puromycin aminonucleoside.,"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.","[{'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 69, 'end': 87, 'mesh': 'D009404'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 110, 'end': 135, 'mesh': 'D011692'}, {'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 232, 'end': 250, 'mesh': 'D009404'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 262, 'end': 287, 'mesh': 'D011692'}, {'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 300, 'end': 318, 'mesh': 'D009404'}, {'text': 'aminonucleoside', 'type': 'Chemical', 'start': 356, 'end': 371, 'mesh': 'D011692'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 501, 'end': 526, 'mesh': 'D011692'}, {'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 583, 'end': 601, 'mesh': 'D009404'}, {'text': 'albuminuria', 'type': 'Disease', 'start': 617, 'end': 628, 'mesh': 'D000419'}, {'text': 'nephrotic', 'type': 'Disease', 'start': 720, 'end': 729, 'mesh': 'D009404'}, {'text': 'nephrotic', 'type': 'Disease', 'start': 750, 'end': 759, 'mesh': 'D009404'}, {'text': 'nephrotic', 'type': 'Disease', 'start': 785, 'end': 794, 'mesh': 'D009404'}, {'text': 'fatty acids', 'type': 'Chemical', 'start': 821, 'end': 832, 'mesh': 'D005227'}, {'text': 'triacylglycerol', 'type': 'Chemical', 'start': 834, 'end': 849, 'mesh': 'D014280'}, {'text': 'cholesteryl esters', 'type': 'Chemical', 'start': 897, 'end': 915, 'mesh': 'D002788'}, {'text': 'nephrotic', 'type': 'Disease', 'start': 1033, 'end': 1042, 'mesh': 'D009404'}, {'text': 'nephrotic', 'type': 'Disease', 'start': 1512, 'end': 1521, 'mesh': 'D009404'}, {'text': 'nephrotic', 'type': 'Disease', 'start': 1579, 'end': 1588, 'mesh': 'D009404'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 1693, 'end': 1718, 'mesh': 'D011692'}, {'text': 'nephrotic', 'type': 'Disease', 'start': 1856, 'end': 1865, 'mesh': 'D009404'}]"
+709,7007443,Circulating lysosomal enzymes and acute hepatic necrosis.,"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.","[{'text': 'acute hepatic necrosis', 'type': 'Disease', 'start': 34, 'end': 56, 'mesh': 'D017114'}, {'text': 'fulminant hepatic failure', 'type': 'Disease', 'start': 215, 'end': 240, 'mesh': 'D017114'}, {'text': 'fulminant hepatic failure', 'type': 'Disease', 'start': 370, 'end': 395, 'mesh': 'D017114'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 402, 'end': 413, 'mesh': 'D000082'}, {'text': 'overdose', 'type': 'Disease', 'start': 414, 'end': 422, 'mesh': 'D062787'}, {'text': 'fulminant hepatic failure', 'type': 'Disease', 'start': 483, 'end': 508, 'mesh': 'D017114'}, {'text': 'viral hepatitis', 'type': 'Disease', 'start': 516, 'end': 531, 'mesh': 'D006525'}, {'text': 'aspartate', 'type': 'Chemical', 'start': 732, 'end': 741, 'mesh': 'D001224'}]"
+710,3762968,Transketolase abnormality in tolazamide-induced Wernicke's encephalopathy.,"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.","[{'text': 'tolazamide', 'type': 'Chemical', 'start': 29, 'end': 39, 'mesh': 'D014042'}, {'text': ""Wernicke's encephalopathy"", 'type': 'Disease', 'start': 48, 'end': 73, 'mesh': 'D014899'}, {'text': 'thiamine', 'type': 'Chemical', 'start': 88, 'end': 96, 'mesh': 'D013831'}, {'text': 'diabetic', 'type': 'Disease', 'start': 152, 'end': 160, 'mesh': 'D003920'}, {'text': ""Wernicke's encephalopathy"", 'type': 'Disease', 'start': 183, 'end': 208, 'mesh': 'D014899'}, {'text': 'tolazamide', 'type': 'Chemical', 'start': 227, 'end': 237, 'mesh': 'D014042'}, {'text': 'thiamine pyrophosphate', 'type': 'Chemical', 'start': 325, 'end': 347, 'mesh': 'D013835'}, {'text': 'TPP', 'type': 'Chemical', 'start': 349, 'end': 352, 'mesh': 'D013835'}, {'text': 'Wernicke-Korsakoff syndrome', 'type': 'Disease', 'start': 396, 'end': 423, 'mesh': 'D020915'}, {'text': 'diabetic', 'type': 'Disease', 'start': 493, 'end': 501, 'mesh': 'D003920'}, {'text': ""Wernicke's encephalopathy"", 'type': 'Disease', 'start': 534, 'end': 559, 'mesh': 'D014899'}, {'text': 'diabetic', 'type': 'Disease', 'start': 648, 'end': 656, 'mesh': 'D003920'}, {'text': ""Wernicke's encephalopathy"", 'type': 'Disease', 'start': 685, 'end': 710, 'mesh': 'D014899'}, {'text': 'TPP', 'type': 'Chemical', 'start': 766, 'end': 769, 'mesh': 'D013835'}, {'text': 'Wernicke-Korsakoff syndrome', 'type': 'Disease', 'start': 825, 'end': 852, 'mesh': 'D020915'}, {'text': 'tolazamide', 'type': 'Chemical', 'start': 874, 'end': 884, 'mesh': 'D014042'}, {'text': ""Wernicke's encephalopathy"", 'type': 'Disease', 'start': 893, 'end': 918, 'mesh': 'D014899'}]"
+711,3413271,Mechanisms of myocardial ischemia induced by epinephrine: comparison with exercise-induced ischemia.,"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.","[{'text': 'myocardial ischemia', 'type': 'Disease', 'start': 14, 'end': 33, 'mesh': 'D017202'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 45, 'end': 56, 'mesh': 'D004837'}, {'text': 'ischemia', 'type': 'Disease', 'start': 91, 'end': 99, 'mesh': 'D007511'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 113, 'end': 124, 'mesh': 'D004837'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 138, 'end': 157, 'mesh': 'D017202'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 188, 'end': 211, 'mesh': 'D003324'}, {'text': 'ischemia', 'type': 'Disease', 'start': 232, 'end': 240, 'mesh': 'D007511'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 275, 'end': 281, 'mesh': 'D010100'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 315, 'end': 326, 'mesh': 'D004837'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 370, 'end': 381, 'mesh': 'D004837'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 404, 'end': 423, 'mesh': 'D017202'}, {'text': 'depression', 'type': 'Disease', 'start': 451, 'end': 461, 'mesh': 'D003866'}, {'text': 'angina', 'type': 'Disease', 'start': 466, 'end': 472, 'mesh': 'D000787'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 501, 'end': 520, 'mesh': 'D017202'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 532, 'end': 543, 'mesh': 'D004837'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 614, 'end': 633, 'mesh': 'D017202'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 766, 'end': 777, 'mesh': 'D004837'}, {'text': 'ischemia', 'type': 'Disease', 'start': 786, 'end': 794, 'mesh': 'D007511'}, {'text': 'ischemia', 'type': 'Disease', 'start': 952, 'end': 960, 'mesh': 'D007511'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 973, 'end': 984, 'mesh': 'D004837'}]"
+712,3088349,Transient contralateral rotation following unilateral substantia nigra lesion reflects susceptibility of the nigrostriatal system to exhaustion by amphetamine.,"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.","[{'text': 'contralateral rotation', 'type': 'Disease', 'start': 10, 'end': 32, 'mesh': 'D009069'}, {'text': 'substantia nigra lesion', 'type': 'Disease', 'start': 54, 'end': 77, 'mesh': '-1'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 147, 'end': 158, 'mesh': 'D000661'}, {'text': '6-OHDA', 'type': 'Chemical', 'start': 181, 'end': 187, 'mesh': 'D016627'}, {'text': 'SN lesion', 'type': 'Disease', 'start': 196, 'end': 205, 'mesh': '-1'}, {'text': 'contralateral rotation', 'type': 'Disease', 'start': 229, 'end': 251, 'mesh': 'D009069'}, {'text': 'ipsilateral circling', 'type': 'Disease', 'start': 297, 'end': 317, 'mesh': 'D009069'}, {'text': 'contralateral rotation', 'type': 'Disease', 'start': 366, 'end': 388, 'mesh': 'D009069'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 468, 'end': 479, 'mesh': 'D000661'}, {'text': 'rotational behavior', 'type': 'Disease', 'start': 488, 'end': 507, 'mesh': 'D009069'}, {'text': 'contralateral rotation', 'type': 'Disease', 'start': 601, 'end': 623, 'mesh': 'D009069'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 831, 'end': 842, 'mesh': 'D000661'}, {'text': 'contralateral rotation', 'type': 'Disease', 'start': 950, 'end': 972, 'mesh': 'D009069'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1065, 'end': 1076, 'mesh': 'D000661'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1115, 'end': 1126, 'mesh': 'D000661'}, {'text': 'rotation', 'type': 'Disease', 'start': 1135, 'end': 1143, 'mesh': 'D009069'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1299, 'end': 1310, 'mesh': 'D000661'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1351, 'end': 1362, 'mesh': 'D000661'}, {'text': 'contralateral rotation', 'type': 'Disease', 'start': 1433, 'end': 1455, 'mesh': 'D009069'}]"
+713,3001299,Thyroid function and urine-concentrating ability during lithium treatment.,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.,"[{'text': 'lithium', 'type': 'Chemical', 'start': 56, 'end': 63, 'mesh': 'D008094'}, {'text': 'nephrogenic diabetes insipidus', 'type': 'Disease', 'start': 175, 'end': 205, 'mesh': 'D018500'}, {'text': 'hypothyroidism', 'type': 'Disease', 'start': 210, 'end': 224, 'mesh': 'D007037'}, {'text': 'lithium', 'type': 'Chemical', 'start': 232, 'end': 239, 'mesh': 'D008094'}, {'text': 'thyroxine', 'type': 'Chemical', 'start': 269, 'end': 278, 'mesh': 'D013974'}, {'text': 'lithium', 'type': 'Chemical', 'start': 379, 'end': 386, 'mesh': 'D008094'}, {'text': 'Hypothyroidism', 'type': 'Disease', 'start': 388, 'end': 402, 'mesh': 'D007037'}, {'text': 'lithium', 'type': 'Chemical', 'start': 454, 'end': 461, 'mesh': 'D008094'}, {'text': 'hypothyroid', 'type': 'Disease', 'start': 509, 'end': 520, 'mesh': 'D007037'}, {'text': 'hypothyroid', 'type': 'Disease', 'start': 541, 'end': 552, 'mesh': 'D007037'}, {'text': 'lithium', 'type': 'Chemical', 'start': 647, 'end': 654, 'mesh': 'D008094'}]"
+714,2004015,Sensitivity of erythroid progenitor colonies to erythropoietin in azidothymidine treated immunodeficient mice.,"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.","[{'text': 'azidothymidine', 'type': 'Chemical', 'start': 66, 'end': 80, 'mesh': 'D015215'}, {'text': 'immunodeficient', 'type': 'Disease', 'start': 89, 'end': 104, 'mesh': 'C565469'}, {'text': 'anaemia', 'type': 'Disease', 'start': 115, 'end': 122, 'mesh': 'D000740'}, {'text': ""3'-azido-3'dideoxythymidine"", 'type': 'Chemical', 'start': 134, 'end': 161, 'mesh': 'D015215'}, {'text': 'AZT', 'type': 'Chemical', 'start': 163, 'end': 166, 'mesh': 'D015215'}, {'text': 'AIDS', 'type': 'Disease', 'start': 221, 'end': 225, 'mesh': 'D000163'}, {'text': 'infection', 'type': 'Disease', 'start': 227, 'end': 236, 'mesh': 'D007239'}, {'text': 'leukaemia', 'type': 'Disease', 'start': 279, 'end': 288, 'mesh': 'D007938'}, {'text': 'AZT', 'type': 'Chemical', 'start': 319, 'end': 322, 'mesh': 'D015215'}, {'text': 'anaemia', 'type': 'Disease', 'start': 331, 'end': 338, 'mesh': 'D000740'}, {'text': 'AZT', 'type': 'Chemical', 'start': 504, 'end': 507, 'mesh': 'D015215'}, {'text': 'AZT', 'type': 'Chemical', 'start': 554, 'end': 557, 'mesh': 'D015215'}, {'text': 'anaemia', 'type': 'Disease', 'start': 567, 'end': 574, 'mesh': 'D000740'}, {'text': 'anaemia', 'type': 'Disease', 'start': 632, 'end': 639, 'mesh': 'D000740'}, {'text': 'AZT', 'type': 'Chemical', 'start': 688, 'end': 691, 'mesh': 'D015215'}, {'text': 'AZT', 'type': 'Chemical', 'start': 920, 'end': 923, 'mesh': 'D015215'}, {'text': 'AZT', 'type': 'Chemical', 'start': 1158, 'end': 1161, 'mesh': 'D015215'}, {'text': 'anaemia', 'type': 'Disease', 'start': 1210, 'end': 1217, 'mesh': 'D000740'}, {'text': 'phenylhydrazine', 'type': 'Chemical', 'start': 1246, 'end': 1261, 'mesh': 'C030299'}, {'text': 'PHZ', 'type': 'Chemical', 'start': 1263, 'end': 1266, 'mesh': 'C030299'}, {'text': 'AZT', 'type': 'Chemical', 'start': 1379, 'end': 1382, 'mesh': 'D015215'}, {'text': 'PHZ', 'type': 'Chemical', 'start': 1387, 'end': 1390, 'mesh': 'C030299'}, {'text': 'anaemia', 'type': 'Disease', 'start': 1428, 'end': 1435, 'mesh': 'D000740'}, {'text': 'reticulocytosis', 'type': 'Disease', 'start': 1446, 'end': 1461, 'mesh': 'D045262'}, {'text': 'anaemia', 'type': 'Disease', 'start': 1498, 'end': 1505, 'mesh': 'D000740'}, {'text': 'AZT', 'type': 'Chemical', 'start': 1518, 'end': 1521, 'mesh': 'D015215'}, {'text': 'AZT', 'type': 'Chemical', 'start': 1545, 'end': 1548, 'mesh': 'D015215'}, {'text': 'anaemia', 'type': 'Disease', 'start': 1568, 'end': 1575, 'mesh': 'D000740'}]"
+715,1732442,Detection of abnormal cardiac adrenergic neuron activity in adriamycin-induced cardiomyopathy with iodine-125-metaiodobenzylguanidine.,"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.","[{'text': 'adriamycin', 'type': 'Chemical', 'start': 60, 'end': 70, 'mesh': 'D004317'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 79, 'end': 93, 'mesh': 'D009202'}, {'text': 'iodine-125-metaiodobenzylguanidine', 'type': 'Chemical', 'start': 99, 'end': 133, 'mesh': 'D019797'}, {'text': 'Radiolabeled metaiodobenzylguanidine', 'type': 'Chemical', 'start': 135, 'end': 171, 'mesh': 'D019797'}, {'text': 'MIBG', 'type': 'Chemical', 'start': 173, 'end': 177, 'mesh': 'D019797'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 193, 'end': 207, 'mesh': 'D009638'}, {'text': 'NE', 'type': 'Chemical', 'start': 209, 'end': 211, 'mesh': 'D009638'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 299, 'end': 309, 'mesh': 'D004317'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 318, 'end': 332, 'mesh': 'D009202'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 458, 'end': 468, 'mesh': 'D004317'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 469, 'end': 483, 'mesh': 'D009202'}, {'text': 'vacuolar degeneration of myocardial cells', 'type': 'Disease', 'start': 499, 'end': 540, 'mesh': 'C536522'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 585, 'end': 595, 'mesh': 'D004317'}, {'text': 'MIBG', 'type': 'Chemical', 'start': 967, 'end': 971, 'mesh': 'D019797'}, {'text': 'MIBG', 'type': 'Chemical', 'start': 1318, 'end': 1322, 'mesh': 'D019797'}, {'text': 'MIBG', 'type': 'Chemical', 'start': 1465, 'end': 1469, 'mesh': 'D019797'}, {'text': 'MIBG', 'type': 'Chemical', 'start': 1599, 'end': 1603, 'mesh': 'D019797'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 1651, 'end': 1661, 'mesh': 'D004317'}, {'text': 'myocardial impairment', 'type': 'Disease', 'start': 1773, 'end': 1794, 'mesh': 'D009202'}, {'text': 'vacuolar degeneration', 'type': 'Disease', 'start': 1815, 'end': 1836, 'mesh': 'C536522'}, {'text': 'MIBG', 'type': 'Chemical', 'start': 1853, 'end': 1857, 'mesh': 'D019797'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 1911, 'end': 1921, 'mesh': 'D004317'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 1930, 'end': 1944, 'mesh': 'D009202'}]"
+716,1423339,Amnestic syndrome associated with propranolol toxicity: a case report.,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.,"[{'text': 'Amnestic syndrome', 'type': 'Disease', 'start': 0, 'end': 17, 'mesh': 'D000647'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 34, 'end': 45, 'mesh': 'D011433'}, {'text': 'toxicity', 'type': 'Disease', 'start': 46, 'end': 54, 'mesh': 'D064420'}, {'text': 'Alzheimer', 'type': 'Disease', 'start': 101, 'end': 110, 'mesh': 'D000544'}, {'text': 'dementia', 'type': 'Disease', 'start': 125, 'end': 133, 'mesh': 'D003704'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 149, 'end': 160, 'mesh': 'D011433'}, {'text': 'toxicity', 'type': 'Disease', 'start': 161, 'end': 169, 'mesh': 'D064420'}, {'text': 'toxicity', 'type': 'Disease', 'start': 342, 'end': 350, 'mesh': 'D064420'}]"
+717,921394,Biphasic response of the SA node of the dog heart in vivo to selective administration of ketamine.,"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.","[{'text': 'ketamine', 'type': 'Chemical', 'start': 89, 'end': 97, 'mesh': 'D007649'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 109, 'end': 117, 'mesh': 'D007649'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 245, 'end': 253, 'mesh': 'D007649'}, {'text': 'depression', 'type': 'Disease', 'start': 317, 'end': 327, 'mesh': 'D003866'}, {'text': 'depression', 'type': 'Disease', 'start': 378, 'end': 388, 'mesh': 'D003866'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 574, 'end': 582, 'mesh': 'D007649'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 591, 'end': 602, 'mesh': 'D013610'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 882, 'end': 890, 'mesh': 'D007649'}]"
+718,871943,The use of serum cholinesterase in succinylcholine apnoea.,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.,"[{'text': 'succinylcholine', 'type': 'Chemical', 'start': 35, 'end': 50, 'mesh': 'D013390'}, {'text': 'apnoea', 'type': 'Disease', 'start': 51, 'end': 57, 'mesh': 'D001049'}, {'text': 'apnoea', 'type': 'Disease', 'start': 111, 'end': 117, 'mesh': 'D001049'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 146, 'end': 161, 'mesh': 'D013390'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 612, 'end': 627, 'mesh': 'D013390'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 664, 'end': 679, 'mesh': 'D013390'}, {'text': 'apnoea', 'type': 'Disease', 'start': 680, 'end': 686, 'mesh': 'D001049'}]"
+719,1355091,Orthostatic hypotension occurs following alpha 2-adrenoceptor blockade in chronic prazosin-pretreated conscious spontaneously hypertensive rats.,"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)","[{'text': 'Orthostatic hypotension', 'type': 'Disease', 'start': 0, 'end': 23, 'mesh': 'D007024'}, {'text': 'prazosin', 'type': 'Chemical', 'start': 82, 'end': 90, 'mesh': 'D011224'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 126, 'end': 138, 'mesh': 'D006973'}, {'text': 'prazosin', 'type': 'Chemical', 'start': 199, 'end': 207, 'mesh': 'D011224'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 337, 'end': 349, 'mesh': 'D006973'}, {'text': 'prazosin', 'type': 'Chemical', 'start': 482, 'end': 490, 'mesh': 'D011224'}, {'text': 'rauwolscine', 'type': 'Chemical', 'start': 513, 'end': 524, 'mesh': 'D015016'}, {'text': 'Orthostatic hypotension', 'type': 'Disease', 'start': 543, 'end': 566, 'mesh': 'D007024'}, {'text': 'prazosin', 'type': 'Chemical', 'start': 743, 'end': 751, 'mesh': 'D011224'}, {'text': 'rauwolscine', 'type': 'Chemical', 'start': 774, 'end': 785, 'mesh': 'D015016'}, {'text': 'orthostatic hypotension', 'type': 'Disease', 'start': 839, 'end': 862, 'mesh': 'D007024'}, {'text': 'prazosin', 'type': 'Chemical', 'start': 887, 'end': 895, 'mesh': 'D011224'}, {'text': 'rauwolscine', 'type': 'Chemical', 'start': 947, 'end': 958, 'mesh': 'D015016'}, {'text': 'prazosin', 'type': 'Chemical', 'start': 1033, 'end': 1041, 'mesh': 'D011224'}, {'text': 'prazosin', 'type': 'Chemical', 'start': 1144, 'end': 1152, 'mesh': 'D011224'}, {'text': 'orthostatic hypotension', 'type': 'Disease', 'start': 1256, 'end': 1279, 'mesh': 'D007024'}, {'text': 'prazosin', 'type': 'Chemical', 'start': 1336, 'end': 1344, 'mesh': 'D011224'}, {'text': 'rauwolscine', 'type': 'Chemical', 'start': 1395, 'end': 1406, 'mesh': 'D015016'}, {'text': 'prazosin', 'type': 'Chemical', 'start': 1435, 'end': 1443, 'mesh': 'D011224'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 1603, 'end': 1614, 'mesh': 'D001919'}, {'text': 'cirazoline', 'type': 'Chemical', 'start': 1638, 'end': 1648, 'mesh': 'C014282'}, {'text': 'Abbott-53693', 'type': 'Chemical', 'start': 1703, 'end': 1715, 'mesh': 'C056299'}, {'text': 'noradrenaline', 'type': 'Chemical', 'start': 1752, 'end': 1765, 'mesh': 'D009638'}, {'text': 'prazosin', 'type': 'Chemical', 'start': 1859, 'end': 1867, 'mesh': 'D011224'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 1903, 'end': 1914, 'mesh': 'D001919'}, {'text': 'cirazoline', 'type': 'Chemical', 'start': 1926, 'end': 1936, 'mesh': 'C014282'}, {'text': 'prazosin', 'type': 'Chemical', 'start': 1963, 'end': 1971, 'mesh': 'D011224'}, {'text': 'Abbott-53693', 'type': 'Chemical', 'start': 2076, 'end': 2088, 'mesh': 'C056299'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 2146, 'end': 2157, 'mesh': 'D001919'}, {'text': 'prazosin', 'type': 'Chemical', 'start': 2190, 'end': 2198, 'mesh': 'D011224'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 2255, 'end': 2266, 'mesh': 'D001919'}, {'text': 'noradrenaline', 'type': 'Chemical', 'start': 2288, 'end': 2301, 'mesh': 'D009638'}, {'text': 'prazosin', 'type': 'Chemical', 'start': 2369, 'end': 2377, 'mesh': 'D011224'}]"
+720,8638876,Coexistence of cerebral venous sinus and internal carotid artery thrombosis associated with exogenous sex hormones. A case report.,"A forty-six year-old premenopausal woman developed headache, nausea and vomiting, left hemiparesis and seizure two days after parenteral use of progesterone and estradiol. Diabetes mellitus (DM) was found during admission. Computed tomography showed a hemorrhagic infarct in the right frontal lobe and increased density in the superior sagittal sinus (SSS). Left carotid angiography found occlusion of the left internal carotid artery (ICA). Right carotid angiograms failed to show the SSS and inferior sagittal sinus, suggestive of venous sinus thrombosis. Coexistence of the cerebral artery and the venous sinus occlusion has been described infrequently. 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.","[{'text': 'headache', 'type': 'Disease', 'start': 182, 'end': 190, 'mesh': 'D006261'}, {'text': 'nausea', 'type': 'Disease', 'start': 192, 'end': 198, 'mesh': 'D009325'}, {'text': 'vomiting', 'type': 'Disease', 'start': 203, 'end': 211, 'mesh': 'D014839'}, {'text': 'hemiparesis', 'type': 'Disease', 'start': 218, 'end': 229, 'mesh': 'D010291'}, {'text': 'seizure', 'type': 'Disease', 'start': 234, 'end': 241, 'mesh': 'D012640'}, {'text': 'progesterone', 'type': 'Chemical', 'start': 275, 'end': 287, 'mesh': 'D011374'}, {'text': 'estradiol', 'type': 'Chemical', 'start': 292, 'end': 301, 'mesh': 'D004958'}, {'text': 'Diabetes mellitus', 'type': 'Disease', 'start': 303, 'end': 320, 'mesh': 'D003920'}, {'text': 'DM', 'type': 'Disease', 'start': 322, 'end': 324, 'mesh': 'D003920'}, {'text': 'occlusion of the left internal carotid artery', 'type': 'Disease', 'start': 520, 'end': 565, 'mesh': 'D001157'}, {'text': 'venous sinus thrombosis', 'type': 'Disease', 'start': 664, 'end': 687, 'mesh': 'D012851'}, {'text': 'estradiol', 'type': 'Chemical', 'start': 840, 'end': 849, 'mesh': 'D004958'}, {'text': 'progesterone', 'type': 'Chemical', 'start': 854, 'end': 866, 'mesh': 'D011374'}, {'text': 'DM', 'type': 'Disease', 'start': 886, 'end': 888, 'mesh': 'D003920'}]"
+721,1628552,Chloroquine related complete heart block with blindness: case report.,"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.","[{'text': 'Chloroquine', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D002738'}, {'text': 'heart block', 'type': 'Disease', 'start': 29, 'end': 40, 'mesh': 'D006327'}, {'text': 'blindness', 'type': 'Disease', 'start': 46, 'end': 55, 'mesh': 'D001766'}, {'text': 'chloroquine', 'type': 'Chemical', 'start': 122, 'end': 133, 'mesh': 'D002738'}, {'text': 'deterioration of vision', 'type': 'Disease', 'start': 171, 'end': 194, 'mesh': 'D015354'}, {'text': 'fatiguability', 'type': 'Disease', 'start': 201, 'end': 214, 'mesh': 'D005221'}, {'text': 'dyspnoea', 'type': 'Disease', 'start': 216, 'end': 224, 'mesh': 'D004417'}, {'text': 'dizziness', 'type': 'Disease', 'start': 226, 'end': 235, 'mesh': 'D004244'}, {'text': 'syncopal attacks', 'type': 'Disease', 'start': 251, 'end': 267, 'mesh': 'D013575'}, {'text': 'chloroquine', 'type': 'Chemical', 'start': 318, 'end': 329, 'mesh': 'D002738'}, {'text': 'retinopathy', 'type': 'Disease', 'start': 330, 'end': 341, 'mesh': 'D012164'}, {'text': 'heart failure', 'type': 'Disease', 'start': 383, 'end': 396, 'mesh': 'D006333'}, {'text': 'heart block', 'type': 'Disease', 'start': 412, 'end': 423, 'mesh': 'D006327'}, {'text': 'right bundle branch block', 'type': 'Disease', 'start': 429, 'end': 454, 'mesh': 'D002037'}, {'text': 'heart block', 'type': 'Disease', 'start': 468, 'end': 479, 'mesh': 'D006327'}, {'text': 'heart failure', 'type': 'Disease', 'start': 523, 'end': 536, 'mesh': 'D006333'}, {'text': 'chloroquine', 'type': 'Chemical', 'start': 570, 'end': 581, 'mesh': 'D002738'}, {'text': 'blind', 'type': 'Disease', 'start': 619, 'end': 624, 'mesh': 'D001766'}]"
+722,11524350,"Systemic toxicity and resuscitation in bupivacaine-, levobupivacaine-, or ropivacaine-infused rats.","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.","[{'text': 'toxicity', 'type': 'Disease', 'start': 9, 'end': 17, 'mesh': 'D064420'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 39, 'end': 50, 'mesh': 'D002045'}, {'text': 'levobupivacaine', 'type': 'Chemical', 'start': 53, 'end': 68, 'mesh': 'C476513'}, {'text': 'ropivacaine', 'type': 'Chemical', 'start': 74, 'end': 85, 'mesh': 'C037663'}, {'text': 'toxicity', 'type': 'Disease', 'start': 125, 'end': 133, 'mesh': 'D064420'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 137, 'end': 148, 'mesh': 'D002045'}, {'text': 'levobupivacaine', 'type': 'Chemical', 'start': 150, 'end': 165, 'mesh': 'C476513'}, {'text': 'ropivacaine', 'type': 'Chemical', 'start': 171, 'end': 182, 'mesh': 'C037663'}, {'text': 'Bupivacaine', 'type': 'Chemical', 'start': 301, 'end': 312, 'mesh': 'D002045'}, {'text': 'levobupivacaine', 'type': 'Chemical', 'start': 314, 'end': 329, 'mesh': 'C476513'}, {'text': 'ropivacaine', 'type': 'Chemical', 'start': 334, 'end': 345, 'mesh': 'C037663'}, {'text': 'asystole', 'type': 'Disease', 'start': 496, 'end': 504, 'mesh': 'D006323'}, {'text': 'Epinephrine', 'type': 'Chemical', 'start': 585, 'end': 596, 'mesh': 'D004837'}, {'text': 'levobupivacaine', 'type': 'Chemical', 'start': 835, 'end': 850, 'mesh': 'C476513'}, {'text': 'ropivacaine', 'type': 'Chemical', 'start': 855, 'end': 866, 'mesh': 'C037663'}, {'text': 'seizures', 'type': 'Disease', 'start': 881, 'end': 889, 'mesh': 'D012640'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 933, 'end': 944, 'mesh': 'D002045'}, {'text': 'levobupivacaine', 'type': 'Chemical', 'start': 970, 'end': 985, 'mesh': 'C476513'}, {'text': 'dysrhythmias', 'type': 'Disease', 'start': 1000, 'end': 1012, 'mesh': 'D001145'}, {'text': 'asystole', 'type': 'Disease', 'start': 1017, 'end': 1025, 'mesh': 'D006323'}, {'text': 'ropivacaine', 'type': 'Chemical', 'start': 1071, 'end': 1082, 'mesh': 'C037663'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 1119, 'end': 1130, 'mesh': 'D002045'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 1228, 'end': 1239, 'mesh': 'D004837'}, {'text': 'Ropivacaine', 'type': 'Chemical', 'start': 1260, 'end': 1271, 'mesh': 'C037663'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1334, 'end': 1342, 'mesh': 'D064420'}, {'text': 'levobupivacaine', 'type': 'Chemical', 'start': 1346, 'end': 1361, 'mesh': 'C476513'}, {'text': 'ropivacaine', 'type': 'Chemical', 'start': 1394, 'end': 1405, 'mesh': 'C037663'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 1410, 'end': 1421, 'mesh': 'D002045'}, {'text': 'ropivacaine', 'type': 'Chemical', 'start': 1466, 'end': 1477, 'mesh': 'C037663'}, {'text': 'cardiac arrest', 'type': 'Disease', 'start': 1486, 'end': 1500, 'mesh': 'D006323'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 1566, 'end': 1577, 'mesh': 'D002045'}, {'text': 'levobupivacaine', 'type': 'Chemical', 'start': 1581, 'end': 1596, 'mesh': 'C476513'}]"
+723,10027919,22-oxacalcitriol suppresses secondary hyperparathyroidism without inducing low bone turnover in dogs with renal failure.,"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.","[{'text': '22-oxacalcitriol', 'type': 'Chemical', 'start': 0, 'end': 16, 'mesh': 'C051883'}, {'text': 'secondary hyperparathyroidism', 'type': 'Disease', 'start': 28, 'end': 57, 'mesh': 'D006962'}, {'text': 'low bone turnover', 'type': 'Disease', 'start': 75, 'end': 92, 'mesh': 'D001851'}, {'text': 'renal failure', 'type': 'Disease', 'start': 106, 'end': 119, 'mesh': 'D051437'}, {'text': 'Calcitriol', 'type': 'Chemical', 'start': 133, 'end': 143, 'mesh': 'D002117'}, {'text': 'renal failure', 'type': 'Disease', 'start': 222, 'end': 235, 'mesh': 'D051437'}, {'text': 'hypercalcemia', 'type': 'Disease', 'start': 273, 'end': 286, 'mesh': 'D006934'}, {'text': 'suppression of bone turnover', 'type': 'Disease', 'start': 301, 'end': 329, 'mesh': 'D001851'}, {'text': 'adynamic bone disease', 'type': 'Disease', 'start': 349, 'end': 370, 'mesh': 'D001851'}, {'text': 'vitamin D', 'type': 'Chemical', 'start': 378, 'end': 387, 'mesh': 'D014807'}, {'text': '22-oxacalcitriol', 'type': 'Chemical', 'start': 398, 'end': 414, 'mesh': 'C051883'}, {'text': 'OCT', 'type': 'Chemical', 'start': 416, 'end': 419, 'mesh': 'C051883'}, {'text': 'OCT', 'type': 'Chemical', 'start': 526, 'end': 529, 'mesh': 'C051883'}, {'text': 'impaired renal function', 'type': 'Disease', 'start': 591, 'end': 614, 'mesh': 'D007674'}, {'text': 'phosphate', 'type': 'Chemical', 'start': 743, 'end': 752, 'mesh': 'D010710'}, {'text': 'phosphate', 'type': 'Chemical', 'start': 813, 'end': 822, 'mesh': 'D010710'}, {'text': 'OCT', 'type': 'Chemical', 'start': 887, 'end': 890, 'mesh': 'C051883'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1110, 'end': 1117, 'mesh': 'D002118'}, {'text': 'OCT', 'type': 'Chemical', 'start': 1230, 'end': 1233, 'mesh': 'C051883'}, {'text': 'OCT', 'type': 'Chemical', 'start': 1317, 'end': 1320, 'mesh': 'C051883'}, {'text': 'renal insufficiency', 'type': 'Disease', 'start': 1390, 'end': 1409, 'mesh': 'D051437'}, {'text': 'secondary hyperparathyroidism', 'type': 'Disease', 'start': 1428, 'end': 1457, 'mesh': 'D006962'}, {'text': 'OCT', 'type': 'Chemical', 'start': 1459, 'end': 1462, 'mesh': 'C051883'}, {'text': 'hypercalcemia', 'type': 'Disease', 'start': 1703, 'end': 1716, 'mesh': 'D006934'}, {'text': 'hyperphosphatemia', 'type': 'Disease', 'start': 1721, 'end': 1738, 'mesh': 'D054559'}, {'text': 'OCT', 'type': 'Chemical', 'start': 1779, 'end': 1782, 'mesh': 'C051883'}, {'text': 'OCT', 'type': 'Chemical', 'start': 1924, 'end': 1927, 'mesh': 'C051883'}, {'text': 'woven osteoid', 'type': 'Disease', 'start': 1970, 'end': 1983, 'mesh': '-1'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 1988, 'end': 1996, 'mesh': 'D005355'}, {'text': 'OCT', 'type': 'Chemical', 'start': 2071, 'end': 2074, 'mesh': 'C051883'}, {'text': 'OCT', 'type': 'Chemical', 'start': 2237, 'end': 2240, 'mesh': 'C051883'}, {'text': 'hypercalcemia', 'type': 'Disease', 'start': 2287, 'end': 2300, 'mesh': 'D006934'}, {'text': 'renal insufficiency', 'type': 'Disease', 'start': 2327, 'end': 2346, 'mesh': 'D051437'}, {'text': 'secondary hyperparathyroidism', 'type': 'Disease', 'start': 2386, 'end': 2415, 'mesh': 'D006962'}, {'text': 'low bone turnover', 'type': 'Disease', 'start': 2443, 'end': 2460, 'mesh': 'D001851'}, {'text': 'adynamic bone disease', 'type': 'Disease', 'start': 2507, 'end': 2528, 'mesh': 'D001851'}]"
+724,8643966,Chemotherapy of advanced inoperable non-small cell lung cancer with paclitaxel: a phase II trial.,"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.","[{'text': 'non-small cell lung cancer', 'type': 'Disease', 'start': 36, 'end': 62, 'mesh': 'D002289'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 68, 'end': 78, 'mesh': 'D017239'}, {'text': 'Paclitaxel', 'type': 'Chemical', 'start': 98, 'end': 108, 'mesh': 'D017239'}, {'text': 'Taxol', 'type': 'Chemical', 'start': 110, 'end': 115, 'mesh': 'D017239'}, {'text': 'tumor', 'type': 'Disease', 'start': 233, 'end': 238, 'mesh': 'D009369'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 315, 'end': 325, 'mesh': 'D017239'}, {'text': 'non-small cell lung cancer', 'type': 'Disease', 'start': 389, 'end': 415, 'mesh': 'D002289'}, {'text': 'NSCLC', 'type': 'Disease', 'start': 417, 'end': 422, 'mesh': 'D002289'}, {'text': 'Leukopenia', 'type': 'Disease', 'start': 464, 'end': 474, 'mesh': 'D007970'}, {'text': 'leukopenia', 'type': 'Disease', 'start': 543, 'end': 553, 'mesh': 'D007970'}, {'text': 'toxicity', 'type': 'Disease', 'start': 588, 'end': 596, 'mesh': 'D064420'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 609, 'end': 619, 'mesh': 'D017239'}, {'text': 'NSCLC', 'type': 'Disease', 'start': 694, 'end': 699, 'mesh': 'D002289'}, {'text': 'NSCLC', 'type': 'Disease', 'start': 874, 'end': 879, 'mesh': 'D002289'}, {'text': 'Paclitaxel', 'type': 'Chemical', 'start': 881, 'end': 891, 'mesh': 'D017239'}, {'text': 'toxicities', 'type': 'Disease', 'start': 1128, 'end': 1138, 'mesh': 'D064420'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 1195, 'end': 1206, 'mesh': 'D009503'}, {'text': 'polyneuropathy', 'type': 'Disease', 'start': 1249, 'end': 1263, 'mesh': 'D011115'}, {'text': 'polyneuropathy', 'type': 'Disease', 'start': 1328, 'end': 1342, 'mesh': 'D011115'}, {'text': 'myalgia', 'type': 'Disease', 'start': 1368, 'end': 1375, 'mesh': 'D063806'}, {'text': 'arthralgia', 'type': 'Disease', 'start': 1376, 'end': 1386, 'mesh': 'D018771'}, {'text': 'Nausea', 'type': 'Disease', 'start': 1463, 'end': 1469, 'mesh': 'D009325'}, {'text': 'vomiting', 'type': 'Disease', 'start': 1474, 'end': 1482, 'mesh': 'D014839'}, {'text': 'Paclitaxel', 'type': 'Chemical', 'start': 1586, 'end': 1596, 'mesh': 'D017239'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1803, 'end': 1811, 'mesh': 'D064420'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 1843, 'end': 1853, 'mesh': 'D017239'}, {'text': 'NSCLC', 'type': 'Disease', 'start': 1895, 'end': 1900, 'mesh': 'D002289'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 1948, 'end': 1958, 'mesh': 'D017239'}]"
+725,6695415,Cerebral hemorrhage associated with phenylpropanolamine in combination with caffeine.,"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.","[{'text': 'Cerebral hemorrhage', 'type': 'Disease', 'start': 0, 'end': 19, 'mesh': 'D002543'}, {'text': 'phenylpropanolamine', 'type': 'Chemical', 'start': 36, 'end': 55, 'mesh': 'D010665'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 76, 'end': 84, 'mesh': 'D002110'}, {'text': 'Phenylpropanolamine', 'type': 'Chemical', 'start': 86, 'end': 105, 'mesh': 'D010665'}, {'text': 'PPA', 'type': 'Chemical', 'start': 107, 'end': 110, 'mesh': 'D010665'}, {'text': 'stroke', 'type': 'Disease', 'start': 183, 'end': 189, 'mesh': 'D020521'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 217, 'end': 225, 'mesh': 'D002110'}, {'text': 'PPA', 'type': 'Chemical', 'start': 296, 'end': 299, 'mesh': 'D010665'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 300, 'end': 308, 'mesh': 'D002110'}, {'text': 'stroke', 'type': 'Disease', 'start': 321, 'end': 327, 'mesh': 'D020521'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 351, 'end': 363, 'mesh': 'D006973'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 578, 'end': 590, 'mesh': 'D006973'}, {'text': 'PPA', 'type': 'Chemical', 'start': 606, 'end': 609, 'mesh': 'D010665'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 610, 'end': 618, 'mesh': 'D002110'}, {'text': 'hypertension', 'type': 'Disease', 'start': 660, 'end': 672, 'mesh': 'D006973'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 702, 'end': 714, 'mesh': 'D006973'}, {'text': 'PPA', 'type': 'Chemical', 'start': 751, 'end': 754, 'mesh': 'D010665'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 755, 'end': 763, 'mesh': 'D002110'}, {'text': 'cerebral hemorrhage', 'type': 'Disease', 'start': 776, 'end': 795, 'mesh': 'D002543'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 810, 'end': 822, 'mesh': 'D006973'}]"
+726,6637851,Long-term efficacy and toxicity of high-dose amiodarone therapy for ventricular tachycardia or ventricular fibrillation.,"Amiodarone was administered to 154 patients who had sustained, symptomatic ventricular tachycardia (VT) (n = 118) or a cardiac arrest (n = 36) and who were refractory to conventional antiarrhythmic drugs. The loading dose was 800 mg/day for 6 weeks and the maintenance dose was 600 mg/day. Sixty-nine percent of patients continued treatment with amiodarone and had no recurrence of symptomatic VT or ventricular fibrillation (VF) over a follow-up of 6 to 52 months (mean +/- standard deviation 14.2 +/- 8.2). Six percent of the patients had a nonfatal recurrence of VT and were successfully managed by continuing amiodarone at a higher dose or by the addition of a conventional antiarrhythmic drug. 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.","[{'text': 'toxicity', 'type': 'Disease', 'start': 23, 'end': 31, 'mesh': 'D064420'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 45, 'end': 55, 'mesh': 'D000638'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 68, 'end': 91, 'mesh': 'D017180'}, {'text': 'ventricular fibrillation', 'type': 'Disease', 'start': 95, 'end': 119, 'mesh': 'D014693'}, {'text': 'Amiodarone', 'type': 'Chemical', 'start': 121, 'end': 131, 'mesh': 'D000638'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 196, 'end': 219, 'mesh': 'D017180'}, {'text': 'VT', 'type': 'Disease', 'start': 221, 'end': 223, 'mesh': 'D017180'}, {'text': 'cardiac arrest', 'type': 'Disease', 'start': 240, 'end': 254, 'mesh': 'D006323'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 467, 'end': 477, 'mesh': 'D000638'}, {'text': 'VT', 'type': 'Disease', 'start': 515, 'end': 517, 'mesh': 'D017180'}, {'text': 'ventricular fibrillation', 'type': 'Disease', 'start': 521, 'end': 545, 'mesh': 'D014693'}, {'text': 'VF', 'type': 'Disease', 'start': 547, 'end': 549, 'mesh': 'D014693'}, {'text': 'VT', 'type': 'Disease', 'start': 687, 'end': 689, 'mesh': 'D017180'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 734, 'end': 744, 'mesh': 'D000638'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 934, 'end': 944, 'mesh': 'D000638'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 975, 'end': 985, 'mesh': 'D000638'}, {'text': 'tremor', 'type': 'Disease', 'start': 1057, 'end': 1063, 'mesh': 'D014202'}, {'text': 'ataxia', 'type': 'Disease', 'start': 1067, 'end': 1073, 'mesh': 'D001259'}, {'text': 'nausea', 'type': 'Disease', 'start': 1081, 'end': 1087, 'mesh': 'D009325'}, {'text': 'anorexia', 'type': 'Disease', 'start': 1092, 'end': 1100, 'mesh': 'D000855'}, {'text': 'visual halos or blurring', 'type': 'Disease', 'start': 1107, 'end': 1131, 'mesh': 'D014786'}, {'text': 'thyroid function abnormalities', 'type': 'Disease', 'start': 1138, 'end': 1168, 'mesh': 'D013959'}, {'text': 'pulmonary interstitial infiltrates', 'type': 'Disease', 'start': 1178, 'end': 1212, 'mesh': '-1'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 1239, 'end': 1249, 'mesh': 'D000638'}, {'text': 'VT', 'type': 'Disease', 'start': 1300, 'end': 1302, 'mesh': 'D017180'}, {'text': 'VF', 'type': 'Disease', 'start': 1306, 'end': 1308, 'mesh': 'D014693'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1380, 'end': 1388, 'mesh': 'D064420'}, {'text': 'VT', 'type': 'Disease', 'start': 1545, 'end': 1547, 'mesh': 'D017180'}, {'text': 'VF', 'type': 'Disease', 'start': 1551, 'end': 1553, 'mesh': 'D014693'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 1587, 'end': 1597, 'mesh': 'D000638'}]"
+727,8800187,Effect of calcium chloride and 4-aminopyridine therapy on desipramine toxicity in rats.,"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.","[{'text': 'calcium chloride', 'type': 'Chemical', 'start': 10, 'end': 26, 'mesh': 'D002122'}, {'text': '4-aminopyridine', 'type': 'Chemical', 'start': 31, 'end': 46, 'mesh': 'D015761'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 58, 'end': 69, 'mesh': 'D003891'}, {'text': 'toxicity', 'type': 'Disease', 'start': 70, 'end': 78, 'mesh': 'D064420'}, {'text': 'Hypotension', 'type': 'Disease', 'start': 100, 'end': 111, 'mesh': 'D007022'}, {'text': 'overdose', 'type': 'Disease', 'start': 176, 'end': 184, 'mesh': 'D062787'}, {'text': 'calcium', 'type': 'Chemical', 'start': 245, 'end': 252, 'mesh': 'D002118'}, {'text': 'calcium', 'type': 'Chemical', 'start': 320, 'end': 327, 'mesh': 'D002118'}, {'text': 'hypotension', 'type': 'Disease', 'start': 381, 'end': 392, 'mesh': 'D007022'}, {'text': 'calcium', 'type': 'Chemical', 'start': 497, 'end': 504, 'mesh': 'D002118'}, {'text': 'overdose', 'type': 'Disease', 'start': 521, 'end': 529, 'mesh': 'D062787'}, {'text': 'CaCl2', 'type': 'Chemical', 'start': 531, 'end': 536, 'mesh': 'D002122'}, {'text': '4-aminopyridine', 'type': 'Chemical', 'start': 541, 'end': 556, 'mesh': 'D015761'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 614, 'end': 625, 'mesh': 'D003891'}, {'text': 'hypotension', 'type': 'Disease', 'start': 640, 'end': 651, 'mesh': 'D007022'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 675, 'end': 686, 'mesh': 'D001919'}, {'text': 'CaCl2', 'type': 'Chemical', 'start': 724, 'end': 729, 'mesh': 'D002122'}, {'text': 'NaHCO3', 'type': 'Chemical', 'start': 731, 'end': 737, 'mesh': 'D017693'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 813, 'end': 824, 'mesh': 'D003891'}, {'text': '4-aminopyridine', 'type': 'Chemical', 'start': 850, 'end': 865, 'mesh': 'D015761'}, {'text': 'NaHCO3', 'type': 'Chemical', 'start': 886, 'end': 892, 'mesh': 'D017693'}, {'text': 'hypotension', 'type': 'Disease', 'start': 918, 'end': 929, 'mesh': 'D007022'}, {'text': 'CaCl2', 'type': 'Chemical', 'start': 952, 'end': 957, 'mesh': 'D002122'}, {'text': '4-aminopyridine', 'type': 'Chemical', 'start': 962, 'end': 977, 'mesh': 'D015761'}, {'text': 'ventricular arrhythmias', 'type': 'Disease', 'start': 1029, 'end': 1052, 'mesh': 'D001145'}, {'text': 'seizures', 'type': 'Disease', 'start': 1069, 'end': 1077, 'mesh': 'D012640'}, {'text': 'CaCl2', 'type': 'Chemical', 'start': 1096, 'end': 1101, 'mesh': 'D002122'}, {'text': 'CaCl2', 'type': 'Chemical', 'start': 1176, 'end': 1181, 'mesh': 'D002122'}, {'text': '4-aminopyridine', 'type': 'Chemical', 'start': 1185, 'end': 1200, 'mesh': 'D015761'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1250, 'end': 1261, 'mesh': 'D007022'}, {'text': 'CaCl2', 'type': 'Chemical', 'start': 1271, 'end': 1276, 'mesh': 'D002122'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1403, 'end': 1410, 'mesh': 'D002118'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1486, 'end': 1497, 'mesh': 'D007022'}]"
+728,7707116,Phase I trial of 13-cis-retinoic acid in children with neuroblastoma following bone marrow transplantation.,"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.","[{'text': '13-cis-retinoic acid', 'type': 'Chemical', 'start': 17, 'end': 37, 'mesh': 'D015474'}, {'text': 'neuroblastoma', 'type': 'Disease', 'start': 55, 'end': 68, 'mesh': 'D009447'}, {'text': 'neuroblastoma', 'type': 'Disease', 'start': 130, 'end': 143, 'mesh': 'D009447'}, {'text': '13-cis-retinoic acid', 'type': 'Chemical', 'start': 160, 'end': 180, 'mesh': 'D015474'}, {'text': 'cis-RA', 'type': 'Chemical', 'start': 182, 'end': 188, 'mesh': 'D015474'}, {'text': 'cis-RA', 'type': 'Chemical', 'start': 245, 'end': 251, 'mesh': 'D015474'}, {'text': 'neuroblastoma', 'type': 'Disease', 'start': 291, 'end': 304, 'mesh': 'D009447'}, {'text': 'toxicities', 'type': 'Disease', 'start': 463, 'end': 473, 'mesh': 'D064420'}, {'text': 'cis-RA', 'type': 'Chemical', 'start': 499, 'end': 505, 'mesh': 'D015474'}, {'text': 'neuroblastoma', 'type': 'Disease', 'start': 564, 'end': 577, 'mesh': 'D009447'}, {'text': 'cis-RA', 'type': 'Chemical', 'start': 721, 'end': 727, 'mesh': 'D015474'}, {'text': 'toxicity', 'type': 'Disease', 'start': 912, 'end': 920, 'mesh': 'D064420'}, {'text': 'cis-RA', 'type': 'Chemical', 'start': 1014, 'end': 1020, 'mesh': 'D015474'}, {'text': 'toxicities', 'type': 'Disease', 'start': 1052, 'end': 1062, 'mesh': 'D064420'}, {'text': 'hypercalcemia', 'type': 'Disease', 'start': 1111, 'end': 1124, 'mesh': 'D006934'}, {'text': 'rash', 'type': 'Disease', 'start': 1134, 'end': 1138, 'mesh': 'D005076'}, {'text': 'anemia', 'type': 'Disease', 'start': 1152, 'end': 1158, 'mesh': 'D000740'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 1159, 'end': 1175, 'mesh': 'D013921'}, {'text': 'emesis', 'type': 'Disease', 'start': 1176, 'end': 1182, 'mesh': 'D014839'}, {'text': 'rash', 'type': 'Disease', 'start': 1183, 'end': 1187, 'mesh': 'D005076'}, {'text': 'toxicities', 'type': 'Disease', 'start': 1201, 'end': 1211, 'mesh': 'D064420'}, {'text': 'cis-RA', 'type': 'Chemical', 'start': 1227, 'end': 1233, 'mesh': 'D015474'}, {'text': 'metastases', 'type': 'Disease', 'start': 1301, 'end': 1311, 'mesh': 'D009362'}, {'text': 'cis-RA', 'type': 'Chemical', 'start': 1522, 'end': 1528, 'mesh': 'D015474'}, {'text': 'neuroblastoma', 'type': 'Disease', 'start': 1625, 'end': 1638, 'mesh': 'D009447'}, {'text': 'hypercalcemia', 'type': 'Disease', 'start': 1693, 'end': 1706, 'mesh': 'D006934'}, {'text': 'cis-RA', 'type': 'Chemical', 'start': 1738, 'end': 1744, 'mesh': 'D015474'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1773, 'end': 1780, 'mesh': 'D002118'}, {'text': 'cis-RA', 'type': 'Chemical', 'start': 1785, 'end': 1791, 'mesh': 'D015474'}]"
+729,6892185,Effect of calcium chloride on gross behavioural changes produced by carbachol and eserine in cats.,"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.","[{'text': 'calcium chloride', 'type': 'Chemical', 'start': 10, 'end': 26, 'mesh': 'D002122'}, {'text': 'carbachol', 'type': 'Chemical', 'start': 68, 'end': 77, 'mesh': 'D002217'}, {'text': 'eserine', 'type': 'Chemical', 'start': 82, 'end': 89, 'mesh': 'D010830'}, {'text': 'calcium chloride', 'type': 'Chemical', 'start': 113, 'end': 129, 'mesh': 'D002122'}, {'text': 'mydriasis', 'type': 'Disease', 'start': 332, 'end': 341, 'mesh': 'D015878'}, {'text': 'tremor', 'type': 'Disease', 'start': 343, 'end': 349, 'mesh': 'D014202'}, {'text': 'clonic-tonic convulsions', 'type': 'Disease', 'start': 354, 'end': 378, 'mesh': 'D004830'}, {'text': 'carbachol', 'type': 'Chemical', 'start': 391, 'end': 400, 'mesh': 'D002217'}, {'text': 'eserine', 'type': 'Chemical', 'start': 405, 'end': 412, 'mesh': 'D010830'}, {'text': 'Calcium chloride', 'type': 'Chemical', 'start': 450, 'end': 466, 'mesh': 'D002122'}, {'text': 'carbachol', 'type': 'Chemical', 'start': 545, 'end': 554, 'mesh': 'D002217'}, {'text': 'eserine', 'type': 'Chemical', 'start': 559, 'end': 566, 'mesh': 'D010830'}, {'text': 'mydriasis', 'type': 'Disease', 'start': 587, 'end': 596, 'mesh': 'D015878'}, {'text': 'tremor', 'type': 'Disease', 'start': 598, 'end': 604, 'mesh': 'D014202'}, {'text': 'clonic-tonic convulsions', 'type': 'Disease', 'start': 609, 'end': 633, 'mesh': 'D004830'}, {'text': 'carbachol', 'type': 'Chemical', 'start': 644, 'end': 653, 'mesh': 'D002217'}, {'text': 'eserine', 'type': 'Chemical', 'start': 658, 'end': 665, 'mesh': 'D010830'}, {'text': 'calcium chloride', 'type': 'Chemical', 'start': 700, 'end': 716, 'mesh': 'D002122'}, {'text': 'calcium chloride', 'type': 'Chemical', 'start': 738, 'end': 754, 'mesh': 'D002122'}, {'text': 'mydriasis', 'type': 'Disease', 'start': 841, 'end': 850, 'mesh': 'D015878'}, {'text': 'tremor', 'type': 'Disease', 'start': 852, 'end': 858, 'mesh': 'D014202'}, {'text': 'clonic-tonic convulsions', 'type': 'Disease', 'start': 863, 'end': 887, 'mesh': 'D004830'}, {'text': 'carbachol', 'type': 'Chemical', 'start': 898, 'end': 907, 'mesh': 'D002217'}, {'text': 'eserine', 'type': 'Chemical', 'start': 912, 'end': 919, 'mesh': 'D010830'}, {'text': 'Calcium chloride', 'type': 'Chemical', 'start': 921, 'end': 937, 'mesh': 'D002122'}, {'text': 'carbachol', 'type': 'Chemical', 'start': 990, 'end': 999, 'mesh': 'D002217'}, {'text': 'eserine', 'type': 'Chemical', 'start': 1004, 'end': 1011, 'mesh': 'D010830'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1150, 'end': 1157, 'mesh': 'D002118'}, {'text': 'atropine', 'type': 'Chemical', 'start': 1181, 'end': 1189, 'mesh': 'D001285'}]"
+730,6216862,Multiple side effects of penicillamine therapy in one patient with rheumatoid arthritis.,"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.","[{'text': 'penicillamine', 'type': 'Chemical', 'start': 25, 'end': 38, 'mesh': 'D010396'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 67, 'end': 87, 'mesh': 'D001172'}, {'text': 'Skin rashes', 'type': 'Disease', 'start': 89, 'end': 100, 'mesh': 'D005076'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 102, 'end': 113, 'mesh': 'D011507'}, {'text': 'systemic lupus erythematosus', 'type': 'Disease', 'start': 115, 'end': 143, 'mesh': 'D008180'}, {'text': 'polymyositis', 'type': 'Disease', 'start': 145, 'end': 157, 'mesh': 'D017285'}, {'text': 'myasthenia gravis', 'type': 'Disease', 'start': 162, 'end': 179, 'mesh': 'D009157'}, {'text': 'penicillamine', 'type': 'Chemical', 'start': 223, 'end': 236, 'mesh': 'D010396'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 262, 'end': 282, 'mesh': 'D001172'}, {'text': 'skin lesion', 'type': 'Disease', 'start': 340, 'end': 351, 'mesh': 'D012871'}, {'text': 'elastosis perforans serpiginosa', 'type': 'Disease', 'start': 362, 'end': 393, 'mesh': 'C536202'}, {'text': ""Wilson's disease"", 'type': 'Disease', 'start': 458, 'end': 474, 'mesh': 'D006527'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 500, 'end': 520, 'mesh': 'D001172'}, {'text': 'penicillamine', 'type': 'Chemical', 'start': 534, 'end': 547, 'mesh': 'D010396'}]"
+731,2004,Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs.,"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.","[{'text': 'cardiac arrhythmias', 'type': 'Disease', 'start': 33, 'end': 52, 'mesh': 'D001145'}, {'text': 'phenothiazines', 'type': 'Chemical', 'start': 212, 'end': 226, 'mesh': 'D010640'}, {'text': 'Mellaril', 'type': 'Chemical', 'start': 310, 'end': 318, 'mesh': 'D013881'}, {'text': 'thioridazine', 'type': 'Chemical', 'start': 320, 'end': 332, 'mesh': 'D013881'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 379, 'end': 402, 'mesh': 'D017180'}, {'text': 'Supraventricular tachycardia', 'type': 'Disease', 'start': 451, 'end': 479, 'mesh': 'D013617'}, {'text': 'Thorazine', 'type': 'Chemical', 'start': 515, 'end': 524, 'mesh': 'D002746'}, {'text': 'chlorpromazine', 'type': 'Chemical', 'start': 526, 'end': 540, 'mesh': 'D002746'}, {'text': 'Aventyl', 'type': 'Chemical', 'start': 543, 'end': 550, 'mesh': 'D009661'}, {'text': 'nortriptyline', 'type': 'Chemical', 'start': 552, 'end': 565, 'mesh': 'D009661'}, {'text': 'Elavil', 'type': 'Chemical', 'start': 571, 'end': 577, 'mesh': 'D000639'}, {'text': 'amitriptyline', 'type': 'Chemical', 'start': 579, 'end': 592, 'mesh': 'D000639'}, {'text': 'left bundle branch block', 'type': 'Disease', 'start': 608, 'end': 632, 'mesh': 'D002037'}, {'text': 'ventricular arrhythmias', 'type': 'Disease', 'start': 740, 'end': 763, 'mesh': 'D001145'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 807, 'end': 816, 'mesh': 'D008012'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 939, 'end': 950, 'mesh': 'D011433'}, {'text': 'tachyarrhythmias', 'type': 'Disease', 'start': 996, 'end': 1012, 'mesh': 'D013610'}, {'text': 'heart disease', 'type': 'Disease', 'start': 1187, 'end': 1200, 'mesh': 'D006331'}, {'text': 'cardiac arrhythmias', 'type': 'Disease', 'start': 1208, 'end': 1227, 'mesh': 'D001145'}, {'text': 'heart disease', 'type': 'Disease', 'start': 1271, 'end': 1284, 'mesh': 'D006331'}, {'text': 'cardiac complications', 'type': 'Disease', 'start': 1420, 'end': 1441, 'mesh': 'D005117'}, {'text': 'phenothiazines', 'type': 'Chemical', 'start': 1464, 'end': 1478, 'mesh': 'D010640'}]"
+732,6118280,"Serotonergic drugs, benzodiazepines and baclofen block muscimol-induced myoclonic jerks in a strain of mice.","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.","[{'text': 'benzodiazepines', 'type': 'Chemical', 'start': 20, 'end': 35, 'mesh': 'D001569'}, {'text': 'baclofen', 'type': 'Chemical', 'start': 40, 'end': 48, 'mesh': 'D001418'}, {'text': 'muscimol', 'type': 'Chemical', 'start': 55, 'end': 63, 'mesh': 'D009118'}, {'text': 'myoclonic jerks', 'type': 'Disease', 'start': 72, 'end': 87, 'mesh': 'D009207'}, {'text': 'muscimol', 'type': 'Chemical', 'start': 129, 'end': 137, 'mesh': 'D009118'}, {'text': 'myoclonic jerks', 'type': 'Disease', 'start': 147, 'end': 162, 'mesh': 'D009207'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 333, 'end': 342, 'mesh': 'D012701'}, {'text': '5-hydroxytryptophan', 'type': 'Chemical', 'start': 375, 'end': 394, 'mesh': 'D006916'}, {'text': 'muscimol', 'type': 'Chemical', 'start': 500, 'end': 508, 'mesh': 'D009118'}, {'text': 'l-dopa', 'type': 'Chemical', 'start': 550, 'end': 556, 'mesh': 'D007980'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 620, 'end': 629, 'mesh': 'D012701'}, {'text': 'MK-212', 'type': 'Chemical', 'start': 647, 'end': 653, 'mesh': 'C014896'}, {'text': 'muscimol', 'type': 'Chemical', 'start': 706, 'end': 714, 'mesh': 'D009118'}, {'text': 'benzodiazepines', 'type': 'Chemical', 'start': 723, 'end': 738, 'mesh': 'D001569'}, {'text': 'clonazepam', 'type': 'Chemical', 'start': 740, 'end': 750, 'mesh': 'D002998'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 813, 'end': 821, 'mesh': 'D003975'}, {'text': 'myoclonic jerks', 'type': 'Disease', 'start': 852, 'end': 867, 'mesh': 'D009207'}, {'text': 'baclofen', 'type': 'Chemical', 'start': 879, 'end': 887, 'mesh': 'D001418'}, {'text': 'muscimol', 'type': 'Chemical', 'start': 940, 'end': 948, 'mesh': 'D009118'}, {'text': '5-HTP', 'type': 'Chemical', 'start': 1026, 'end': 1031, 'mesh': 'D006916'}, {'text': 'benzodiazepines', 'type': 'Chemical', 'start': 1040, 'end': 1055, 'mesh': 'D001569'}, {'text': 'myoclonus', 'type': 'Disease', 'start': 1119, 'end': 1128, 'mesh': 'D009207'}, {'text': 'muscimol', 'type': 'Chemical', 'start': 1134, 'end': 1142, 'mesh': 'D009118'}, {'text': 'myoclonus', 'type': 'Disease', 'start': 1151, 'end': 1160, 'mesh': 'D009207'}, {'text': 'MK-212', 'type': 'Chemical', 'start': 1336, 'end': 1342, 'mesh': 'C014896'}, {'text': 'baclofen', 'type': 'Chemical', 'start': 1351, 'end': 1359, 'mesh': 'D001418'}, {'text': 'myoclonus', 'type': 'Disease', 'start': 1390, 'end': 1399, 'mesh': 'D009207'}]"
+733,3703509,Hyperglycemic acidotic coma and death in Kearns-Sayre syndrome.,"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.","[{'text': 'Kearns-Sayre syndrome', 'type': 'Disease', 'start': 41, 'end': 62, 'mesh': 'D007625'}, {'text': 'Kearns-Sayre syndrome', 'type': 'Disease', 'start': 157, 'end': 178, 'mesh': 'D007625'}, {'text': 'prednisone', 'type': 'Chemical', 'start': 213, 'end': 223, 'mesh': 'D011241'}, {'text': 'lethargy', 'type': 'Disease', 'start': 245, 'end': 253, 'mesh': 'D053609'}, {'text': 'somnolence', 'type': 'Disease', 'start': 266, 'end': 276, 'mesh': 'D006970'}, {'text': 'polydipsia', 'type': 'Disease', 'start': 278, 'end': 288, 'mesh': 'D059606'}, {'text': 'polyphagia', 'type': 'Disease', 'start': 290, 'end': 300, 'mesh': 'D006963'}, {'text': 'polyuria', 'type': 'Disease', 'start': 306, 'end': 314, 'mesh': 'D011141'}, {'text': 'coma', 'type': 'Disease', 'start': 367, 'end': 371, 'mesh': 'D003128'}, {'text': 'hypotension', 'type': 'Disease', 'start': 373, 'end': 384, 'mesh': 'D007022'}, {'text': 'hyperglycemia', 'type': 'Disease', 'start': 393, 'end': 406, 'mesh': 'D006943'}, {'text': 'acidosis', 'type': 'Disease', 'start': 412, 'end': 420, 'mesh': 'D000138'}, {'text': 'lactic acidosis', 'type': 'Disease', 'start': 433, 'end': 448, 'mesh': 'D000140'}, {'text': 'ketosis', 'type': 'Disease', 'start': 472, 'end': 479, 'mesh': 'D007662'}, {'text': 'lactate', 'type': 'Chemical', 'start': 502, 'end': 509, 'mesh': 'D019344'}, {'text': 'Respiratory failure', 'type': 'Disease', 'start': 542, 'end': 561, 'mesh': 'D012131'}, {'text': 'metabolic-endocrine failure', 'type': 'Disease', 'start': 713, 'end': 740, 'mesh': '-1'}, {'text': 'Kearns-Sayre syndrome', 'type': 'Disease', 'start': 748, 'end': 769, 'mesh': 'D007625'}]"
+734,20683499,"Effects of active constituents of Crocus sativus L., crocin on streptozocin-induced model of sporadic Alzheimer's disease in male rats.","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.","[{'text': 'crocin', 'type': 'Chemical', 'start': 53, 'end': 59, 'mesh': 'C029036'}, {'text': 'streptozocin', 'type': 'Chemical', 'start': 63, 'end': 75, 'mesh': 'D013311'}, {'text': ""Alzheimer's disease"", 'type': 'Disease', 'start': 102, 'end': 121, 'mesh': 'D000544'}, {'text': 'carotenoids', 'type': 'Chemical', 'start': 181, 'end': 192, 'mesh': 'D002338'}, {'text': 'crocins', 'type': 'Chemical', 'start': 194, 'end': 201, 'mesh': 'C029036'}, {'text': 'crocins', 'type': 'Chemical', 'start': 354, 'end': 361, 'mesh': 'C029036'}, {'text': ""Alzheimer's disease"", 'type': 'Disease', 'start': 374, 'end': 393, 'mesh': 'D000544'}, {'text': 'streptozocin', 'type': 'Chemical', 'start': 435, 'end': 447, 'mesh': 'D013311'}, {'text': 'STZ', 'type': 'Chemical', 'start': 449, 'end': 452, 'mesh': 'D013311'}, {'text': 'crocins', 'type': 'Chemical', 'start': 579, 'end': 586, 'mesh': 'C029036'}, {'text': 'STZ', 'type': 'Chemical', 'start': 609, 'end': 612, 'mesh': 'D013311'}, {'text': 'STZ', 'type': 'Chemical', 'start': 623, 'end': 626, 'mesh': 'D013311'}, {'text': 'crocins', 'type': 'Chemical', 'start': 629, 'end': 636, 'mesh': 'C029036'}, {'text': ""Alzheimer's disease"", 'type': 'Disease', 'start': 666, 'end': 685, 'mesh': 'D000544'}, {'text': 'STZ', 'type': 'Chemical', 'start': 718, 'end': 721, 'mesh': 'D013311'}, {'text': 'STZ', 'type': 'Chemical', 'start': 789, 'end': 792, 'mesh': 'D013311'}, {'text': 'STZ', 'type': 'Chemical', 'start': 826, 'end': 829, 'mesh': 'D013311'}, {'text': 'crocin', 'type': 'Chemical', 'start': 832, 'end': 838, 'mesh': 'C029036'}, {'text': 'crocin', 'type': 'Chemical', 'start': 854, 'end': 860, 'mesh': 'C029036'}, {'text': 'crocin', 'type': 'Chemical', 'start': 975, 'end': 981, 'mesh': 'C029036'}, {'text': 'crocin', 'type': 'Chemical', 'start': 1210, 'end': 1216, 'mesh': 'C029036'}, {'text': 'STZ', 'type': 'Chemical', 'start': 1236, 'end': 1239, 'mesh': 'D013311'}, {'text': 'STZ', 'type': 'Chemical', 'start': 1330, 'end': 1333, 'mesh': 'D013311'}, {'text': 'crocin', 'type': 'Chemical', 'start': 1362, 'end': 1368, 'mesh': 'C029036'}, {'text': 'STZ', 'type': 'Chemical', 'start': 1464, 'end': 1467, 'mesh': 'D013311'}, {'text': 'crocin', 'type': 'Chemical', 'start': 1580, 'end': 1586, 'mesh': 'C029036'}, {'text': 'cognitive deficits', 'type': 'Disease', 'start': 1618, 'end': 1636, 'mesh': 'D003072'}, {'text': 'STZ', 'type': 'Chemical', 'start': 1647, 'end': 1650, 'mesh': 'D013311'}, {'text': 'neurodegenerative diseases', 'type': 'Disease', 'start': 1701, 'end': 1727, 'mesh': 'D019636'}, {'text': ""Alzheimer's disease"", 'type': 'Disease', 'start': 1736, 'end': 1755, 'mesh': 'D000544'}]"
+735,20466178,Rosaceiform dermatitis associated with topical tacrolimus treatment.,"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.","[{'text': 'dermatitis', 'type': 'Disease', 'start': 12, 'end': 22, 'mesh': 'D003872'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 47, 'end': 57, 'mesh': 'D016559'}, {'text': 'rosacea', 'type': 'Disease', 'start': 113, 'end': 120, 'mesh': 'D012393'}, {'text': 'dermatitis', 'type': 'Disease', 'start': 126, 'end': 136, 'mesh': 'D003872'}, {'text': 'eruptions', 'type': 'Disease', 'start': 137, 'end': 146, 'mesh': 'D003875'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 173, 'end': 183, 'mesh': 'D016559'}, {'text': 'facial dermatitis', 'type': 'Disease', 'start': 197, 'end': 214, 'mesh': 'D005148'}, {'text': 'telangiectasia', 'type': 'Disease', 'start': 245, 'end': 259, 'mesh': 'D013684'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 403, 'end': 413, 'mesh': 'D016559'}, {'text': 'pimecrolimus', 'type': 'Chemical', 'start': 417, 'end': 429, 'mesh': 'C117268'}, {'text': 'dermatitis', 'type': 'Disease', 'start': 485, 'end': 495, 'mesh': 'D003872'}]"
+736,19944736,A novel animal model to evaluate the ability of a drug delivery system to promote the passage through the BBB.,"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.","[{'text': 'poly-L-lactid acid', 'type': 'Chemical', 'start': 425, 'end': 443, 'mesh': '-1'}, {'text': 'Tacrine', 'type': 'Chemical', 'start': 539, 'end': 546, 'mesh': 'D013619'}, {'text': 'LiCl', 'type': 'Chemical', 'start': 564, 'end': 568, 'mesh': 'D018021'}, {'text': 'seizures', 'type': 'Disease', 'start': 617, 'end': 625, 'mesh': 'D012640'}, {'text': 'hippocampal damage', 'type': 'Disease', 'start': 638, 'end': 656, 'mesh': 'D001930'}, {'text': 'tacrine', 'type': 'Chemical', 'start': 679, 'end': 686, 'mesh': 'D013619'}, {'text': 'poly-L-lactid acid', 'type': 'Chemical', 'start': 694, 'end': 712, 'mesh': '-1'}, {'text': 'tacrine', 'type': 'Chemical', 'start': 758, 'end': 765, 'mesh': 'D013619'}, {'text': 'LiCl', 'type': 'Chemical', 'start': 869, 'end': 873, 'mesh': 'D018021'}, {'text': 'tacrine', 'type': 'Chemical', 'start': 928, 'end': 935, 'mesh': 'D013619'}, {'text': 'epileptic', 'type': 'Disease', 'start': 1013, 'end': 1022, 'mesh': 'D004827'}, {'text': 'tacrine', 'type': 'Chemical', 'start': 1138, 'end': 1145, 'mesh': 'D013619'}, {'text': 'damage of neuronal cells', 'type': 'Disease', 'start': 1190, 'end': 1214, 'mesh': 'D001930'}, {'text': 'tacrine', 'type': 'Chemical', 'start': 1300, 'end': 1307, 'mesh': 'D013619'}, {'text': 'tacrine', 'type': 'Chemical', 'start': 1545, 'end': 1552, 'mesh': 'D013619'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1553, 'end': 1560, 'mesh': 'D008094'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 1570, 'end': 1578, 'mesh': 'D004827'}]"
+737,19721134,The antiarrhythmic effect and possible ionic mechanisms of pilocarpine on animal models.,"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.","[{'text': 'pilocarpine', 'type': 'Chemical', 'start': 59, 'end': 70, 'mesh': 'D010862'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 140, 'end': 151, 'mesh': 'D010862'}, {'text': 'aconitine', 'type': 'Chemical', 'start': 207, 'end': 216, 'mesh': 'D000157'}, {'text': 'ouabain', 'type': 'Chemical', 'start': 233, 'end': 240, 'mesh': 'D010042'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 260, 'end': 270, 'mesh': 'D001145'}, {'text': 'calcium', 'type': 'Chemical', 'start': 338, 'end': 345, 'mesh': 'D002118'}, {'text': 'Ca', 'type': 'Chemical', 'start': 363, 'end': 365, 'mesh': 'D002118'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 426, 'end': 437, 'mesh': 'D010862'}, {'text': 'arrhythmias', 'type': 'Disease', 'start': 469, 'end': 480, 'mesh': 'D001145'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 561, 'end': 571, 'mesh': 'D001145'}, {'text': 'arrhythmic', 'type': 'Disease', 'start': 614, 'end': 624, 'mesh': 'D001145'}, {'text': 'Ca', 'type': 'Chemical', 'start': 648, 'end': 650, 'mesh': 'D002118'}, {'text': 'aconitine', 'type': 'Chemical', 'start': 679, 'end': 688, 'mesh': 'D000157'}, {'text': 'ouabain', 'type': 'Chemical', 'start': 692, 'end': 699, 'mesh': 'D010042'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 749, 'end': 760, 'mesh': 'D010862'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 788, 'end': 801, 'mesh': 'D000109'}, {'text': '4-DAMP', 'type': 'Chemical', 'start': 830, 'end': 836, 'mesh': 'C042375'}, {'text': '4-diphenylacetoxy-N-methylpiperidine-methiodide', 'type': 'Chemical', 'start': 838, 'end': 885, 'mesh': 'C042375'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 933, 'end': 944, 'mesh': 'D010862'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 970, 'end': 981, 'mesh': 'D010862'}, {'text': 'arrhythmic', 'type': 'Disease', 'start': 1017, 'end': 1027, 'mesh': 'D001145'}, {'text': 'aconitine', 'type': 'Chemical', 'start': 1065, 'end': 1074, 'mesh': 'D000157'}, {'text': 'ouabain', 'type': 'Chemical', 'start': 1078, 'end': 1085, 'mesh': 'D010042'}, {'text': 'Ca', 'type': 'Chemical', 'start': 1177, 'end': 1179, 'mesh': 'D002118'}]"
+738,17786501,Disulfiram-induced transient optic and peripheral neuropathy: a case report.,"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.","[{'text': 'Disulfiram', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D004221'}, {'text': 'disulfiram', 'type': 'Chemical', 'start': 155, 'end': 165, 'mesh': 'D004221'}, {'text': 'alcohol dependence', 'type': 'Disease', 'start': 170, 'end': 188, 'mesh': 'D000437'}, {'text': 'loss of vision', 'type': 'Disease', 'start': 290, 'end': 304, 'mesh': 'D014786'}, {'text': 'headaches', 'type': 'Disease', 'start': 336, 'end': 345, 'mesh': 'D006261'}, {'text': 'paraesthesia', 'type': 'Disease', 'start': 382, 'end': 394, 'mesh': 'D010292'}, {'text': 'numbness', 'type': 'Disease', 'start': 400, 'end': 408, 'mesh': 'D006987'}, {'text': 'scotomata', 'type': 'Disease', 'start': 609, 'end': 618, 'mesh': 'D012607'}, {'text': 'disulfiram', 'type': 'Chemical', 'start': 639, 'end': 649, 'mesh': 'D004221'}, {'text': 'alcohol dependence', 'type': 'Disease', 'start': 654, 'end': 672, 'mesh': 'D000437'}, {'text': 'Disulfiram', 'type': 'Chemical', 'start': 700, 'end': 710, 'mesh': 'D004221'}, {'text': 'disulfiram', 'type': 'Chemical', 'start': 817, 'end': 827, 'mesh': 'D004221'}]"
+739,16960342,Sustained clinical improvement of a patient with decompensated hepatitis B virus-related cirrhosis after treatment with lamivudine monotherapy.,"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.","[{'text': 'hepatitis B', 'type': 'Disease', 'start': 63, 'end': 74, 'mesh': 'D006509'}, {'text': 'cirrhosis', 'type': 'Disease', 'start': 89, 'end': 98, 'mesh': 'D005355'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 120, 'end': 130, 'mesh': 'D019259'}, {'text': 'Hepatitis B virus (HBV) infection', 'type': 'Disease', 'start': 144, 'end': 177, 'mesh': 'D006509'}, {'text': 'liver cirrhosis', 'type': 'Disease', 'start': 192, 'end': 207, 'mesh': 'D008103'}, {'text': 'hepatocellular carcinoma', 'type': 'Disease', 'start': 212, 'end': 236, 'mesh': 'D006528'}, {'text': 'cirrhosis', 'type': 'Disease', 'start': 567, 'end': 576, 'mesh': 'D005355'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 841, 'end': 851, 'mesh': 'D019259'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 1289, 'end': 1299, 'mesh': 'D019259'}, {'text': 'cirrhosis', 'type': 'Disease', 'start': 1329, 'end': 1338, 'mesh': 'D005355'}]"
+740,11226639,Dual effects of melatonin on barbiturate-induced narcosis in rats.,"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.","[{'text': 'melatonin', 'type': 'Chemical', 'start': 16, 'end': 25, 'mesh': 'D008550'}, {'text': 'barbiturate', 'type': 'Chemical', 'start': 29, 'end': 40, 'mesh': 'C032232'}, {'text': 'narcosis', 'type': 'Disease', 'start': 49, 'end': 57, 'mesh': 'D053608'}, {'text': 'Melatonin', 'type': 'Chemical', 'start': 67, 'end': 76, 'mesh': 'D008550'}, {'text': 'narcosis', 'type': 'Disease', 'start': 175, 'end': 183, 'mesh': 'D053608'}, {'text': 'Sodium thiopenthal', 'type': 'Chemical', 'start': 185, 'end': 203, 'mesh': 'D013874'}, {'text': 'melatonin', 'type': 'Chemical', 'start': 271, 'end': 280, 'mesh': 'D008550'}, {'text': 'Melatonin', 'type': 'Chemical', 'start': 310, 'end': 319, 'mesh': 'D008550'}, {'text': 'barbiturate', 'type': 'Chemical', 'start': 360, 'end': 371, 'mesh': 'C032232'}, {'text': 'narcosis', 'type': 'Disease', 'start': 372, 'end': 380, 'mesh': 'D053608'}, {'text': 'barbiturate', 'type': 'Chemical', 'start': 507, 'end': 518, 'mesh': 'C032232'}, {'text': 'narcosis', 'type': 'Disease', 'start': 519, 'end': 527, 'mesh': 'D053608'}, {'text': 'melatonin', 'type': 'Chemical', 'start': 562, 'end': 571, 'mesh': 'D008550'}, {'text': 'narcosis', 'type': 'Disease', 'start': 682, 'end': 690, 'mesh': 'D053608'}, {'text': 'Melatonin', 'type': 'Chemical', 'start': 727, 'end': 736, 'mesh': 'D008550'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 800, 'end': 808, 'mesh': 'D007649'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 813, 'end': 821, 'mesh': 'D003975'}, {'text': 'narcosis', 'type': 'Disease', 'start': 830, 'end': 838, 'mesh': 'D053608'}, {'text': 'melatonin', 'type': 'Chemical', 'start': 865, 'end': 874, 'mesh': 'D008550'}, {'text': 'narcosis', 'type': 'Disease', 'start': 894, 'end': 902, 'mesh': 'D053608'}, {'text': 'barbiturate', 'type': 'Chemical', 'start': 932, 'end': 943, 'mesh': 'C032232'}]"
+741,9228650,Effects of NIK-247 on cholinesterase and scopolamine-induced amnesia.,"The effects of NIK-247 on cholinesterase, scopolamine-induced amnesia and spontaneous movement were examined and compared with those of the well-known cholinesterase inhibitors tacrine and E-2020. NIK-247, tacrine and E-2020 all strongly inhibited acetylcholinesterase (AChE) in human red blood cells (IC50s = 1.0 x 10(-6), 2.9 x 10(-7) and 3.7 x 10(-8) M, respectively). In addition, NIK-247 and tacrine, but not E-2020, strongly inhibited butyrylcholinestrase (BuChE) in human serum. All three drugs produced mixed inhibition of AChE activity. Moreover, the inhibitory effect of NIK-247 on AChE was reversible. All compounds at 0.1-1 mg/kg p.o. significantly improved the amnesia induced by scopolamine (0.5 mg/kg s.c.) in rats performing a passive avoidance task. 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 disease.","[{'text': 'NIK-247', 'type': 'Chemical', 'start': 11, 'end': 18, 'mesh': 'C049860'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 41, 'end': 52, 'mesh': 'D012601'}, {'text': 'amnesia', 'type': 'Disease', 'start': 61, 'end': 68, 'mesh': 'D000647'}, {'text': 'NIK-247', 'type': 'Chemical', 'start': 85, 'end': 92, 'mesh': 'C049860'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 112, 'end': 123, 'mesh': 'D012601'}, {'text': 'amnesia', 'type': 'Disease', 'start': 132, 'end': 139, 'mesh': 'D000647'}, {'text': 'tacrine', 'type': 'Chemical', 'start': 247, 'end': 254, 'mesh': 'D013619'}, {'text': 'E-2020', 'type': 'Chemical', 'start': 259, 'end': 265, 'mesh': 'C076946'}, {'text': 'NIK-247', 'type': 'Chemical', 'start': 267, 'end': 274, 'mesh': 'C049860'}, {'text': 'tacrine', 'type': 'Chemical', 'start': 276, 'end': 283, 'mesh': 'D013619'}, {'text': 'E-2020', 'type': 'Chemical', 'start': 288, 'end': 294, 'mesh': 'C076946'}, {'text': 'NIK-247', 'type': 'Chemical', 'start': 455, 'end': 462, 'mesh': 'C049860'}, {'text': 'tacrine', 'type': 'Chemical', 'start': 467, 'end': 474, 'mesh': 'D013619'}, {'text': 'E-2020', 'type': 'Chemical', 'start': 484, 'end': 490, 'mesh': 'C076946'}, {'text': 'NIK-247', 'type': 'Chemical', 'start': 651, 'end': 658, 'mesh': 'C049860'}, {'text': 'amnesia', 'type': 'Disease', 'start': 744, 'end': 751, 'mesh': 'D000647'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 763, 'end': 774, 'mesh': 'D012601'}, {'text': 'NIK-247', 'type': 'Chemical', 'start': 968, 'end': 975, 'mesh': 'C049860'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 1018, 'end': 1029, 'mesh': 'D012601'}, {'text': 'amnesia', 'type': 'Disease', 'start': 1038, 'end': 1045, 'mesh': 'D000647'}, {'text': 'NIK-247', 'type': 'Chemical', 'start': 1114, 'end': 1121, 'mesh': 'C049860'}, {'text': ""Alzheimer's disease"", 'type': 'Disease', 'start': 1164, 'end': 1183, 'mesh': 'D000544'}]"
+742,8766220,Nightmares and hallucinations after long-term intake of tramadol combined with antidepressants.,"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.","[{'text': 'hallucinations', 'type': 'Disease', 'start': 15, 'end': 29, 'mesh': 'D006212'}, {'text': 'tramadol', 'type': 'Chemical', 'start': 56, 'end': 64, 'mesh': 'D014147'}, {'text': 'Tramadol', 'type': 'Chemical', 'start': 96, 'end': 104, 'mesh': 'D014147'}, {'text': 'cancer', 'type': 'Disease', 'start': 206, 'end': 212, 'mesh': 'D009369'}, {'text': 'pain', 'type': 'Disease', 'start': 213, 'end': 217, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 244, 'end': 248, 'mesh': 'D010146'}, {'text': 'paroxetine', 'type': 'Chemical', 'start': 294, 'end': 304, 'mesh': 'D017374'}, {'text': 'dosulepine hydrochloride', 'type': 'Chemical', 'start': 309, 'end': 333, 'mesh': 'D004308'}, {'text': 'tetraparetic', 'type': 'Disease', 'start': 339, 'end': 351, 'mesh': '-1'}, {'text': 'chronic pain', 'type': 'Disease', 'start': 365, 'end': 377, 'mesh': 'D059350'}, {'text': 'hallucinations', 'type': 'Disease', 'start': 450, 'end': 464, 'mesh': 'D006212'}, {'text': 'tramadol', 'type': 'Chemical', 'start': 531, 'end': 539, 'mesh': 'D014147'}, {'text': 'pain', 'type': 'Disease', 'start': 588, 'end': 592, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 660, 'end': 664, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 680, 'end': 684, 'mesh': 'D010146'}]"
+743,8441146,Apparent cure of rheumatoid arthritis by bone marrow transplantation.,"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.","[{'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 17, 'end': 37, 'mesh': 'D001172'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 156, 'end': 176, 'mesh': 'D001172'}, {'text': 'RA', 'type': 'Disease', 'start': 178, 'end': 180, 'mesh': 'D001172'}, {'text': 'aplastic anemia', 'type': 'Disease', 'start': 263, 'end': 278, 'mesh': 'D000741'}, {'text': 'gold', 'type': 'Chemical', 'start': 299, 'end': 303, 'mesh': 'D006046'}, {'text': 'D-penicillamine', 'type': 'Chemical', 'start': 320, 'end': 335, 'mesh': 'D010396'}, {'text': 'RA', 'type': 'Disease', 'start': 490, 'end': 492, 'mesh': 'D001172'}, {'text': 'RA', 'type': 'Disease', 'start': 577, 'end': 579, 'mesh': 'D001172'}, {'text': 'synovitis', 'type': 'Disease', 'start': 817, 'end': 826, 'mesh': 'D013585'}]"
+744,3653576,Urinary enzymes and protein patterns as indicators of injury to different regions of the kidney.,"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.","[{'text': 'injury to different regions of the kidney', 'type': 'Disease', 'start': 54, 'end': 95, 'mesh': 'D007674'}, {'text': 'Acute experimental models of renal damage', 'type': 'Disease', 'start': 97, 'end': 138, 'mesh': 'D058186'}, {'text': 'hexachloro-1:3-butadiene', 'type': 'Chemical', 'start': 244, 'end': 268, 'mesh': 'C001335'}, {'text': 'HCBD', 'type': 'Chemical', 'start': 270, 'end': 274, 'mesh': 'C001335'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 277, 'end': 302, 'mesh': 'D011692'}, {'text': 'PAN', 'type': 'Chemical', 'start': 304, 'end': 307, 'mesh': 'D011692'}, {'text': '2-bromoethylamine', 'type': 'Chemical', 'start': 314, 'end': 331, 'mesh': 'C004504'}, {'text': 'BEA', 'type': 'Chemical', 'start': 333, 'end': 336, 'mesh': 'C004504'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 383, 'end': 397, 'mesh': 'D007674'}, {'text': 'protein excretion', 'type': 'Disease', 'start': 495, 'end': 512, 'mesh': 'D011507'}, {'text': 'HCBD', 'type': 'Chemical', 'start': 574, 'end': 578, 'mesh': 'C001335'}, {'text': 'BEA', 'type': 'Chemical', 'start': 582, 'end': 585, 'mesh': 'C004504'}, {'text': 'glomerular damage', 'type': 'Disease', 'start': 647, 'end': 664, 'mesh': 'D007674'}, {'text': 'PAN', 'type': 'Chemical', 'start': 677, 'end': 680, 'mesh': 'D011692'}, {'text': 'protein excretion', 'type': 'Disease', 'start': 739, 'end': 756, 'mesh': 'D011507'}, {'text': 'protein excretion', 'type': 'Disease', 'start': 837, 'end': 854, 'mesh': 'D011507'}, {'text': 'excretion of proteins', 'type': 'Disease', 'start': 919, 'end': 940, 'mesh': 'D011507'}, {'text': 'HCBD', 'type': 'Chemical', 'start': 1013, 'end': 1017, 'mesh': 'C001335'}, {'text': 'BEA', 'type': 'Chemical', 'start': 1049, 'end': 1052, 'mesh': 'C004504'}, {'text': 'glucose', 'type': 'Chemical', 'start': 1206, 'end': 1213, 'mesh': 'D005947'}, {'text': 'renal damage', 'type': 'Disease', 'start': 1542, 'end': 1554, 'mesh': 'D007674'}]"
+745,2750819,Neuromuscular blockade with magnesium sulfate and nifedipine.,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.,"[{'text': 'Neuromuscular blockade', 'type': 'Disease', 'start': 0, 'end': 22, 'mesh': 'D020879'}, {'text': 'magnesium sulfate', 'type': 'Chemical', 'start': 28, 'end': 45, 'mesh': 'D008278'}, {'text': 'nifedipine', 'type': 'Chemical', 'start': 50, 'end': 60, 'mesh': 'D009543'}, {'text': 'nifedipine', 'type': 'Chemical', 'start': 100, 'end': 110, 'mesh': 'D009543'}, {'text': 'neuromuscular blockade', 'type': 'Disease', 'start': 121, 'end': 143, 'mesh': 'D020879'}, {'text': 'magnesium sulfate', 'type': 'Chemical', 'start': 160, 'end': 177, 'mesh': 'D008278'}, {'text': 'nifedipine', 'type': 'Chemical', 'start': 228, 'end': 238, 'mesh': 'D009543'}, {'text': 'toxicity', 'type': 'Disease', 'start': 268, 'end': 276, 'mesh': 'D064420'}, {'text': 'magnesium', 'type': 'Chemical', 'start': 280, 'end': 289, 'mesh': 'D008274'}]"
+746,1899352,Ifosfamide continuous infusion without mesna. A phase I trial of a 14-day cycle.,"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.","[{'text': 'Ifosfamide', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D007069'}, {'text': 'mesna', 'type': 'Chemical', 'start': 39, 'end': 44, 'mesh': 'D015080'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 120, 'end': 130, 'mesh': 'D007069'}, {'text': 'Mesna', 'type': 'Chemical', 'start': 197, 'end': 202, 'mesh': 'D015080'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 282, 'end': 292, 'mesh': 'D007069'}, {'text': 'Mesna', 'type': 'Chemical', 'start': 378, 'end': 383, 'mesh': 'D015080'}, {'text': 'hematuria', 'type': 'Disease', 'start': 507, 'end': 516, 'mesh': 'D006417'}, {'text': 'hematuria', 'type': 'Disease', 'start': 586, 'end': 595, 'mesh': 'D006417'}, {'text': 'toxicity', 'type': 'Disease', 'start': 652, 'end': 660, 'mesh': 'D064420'}, {'text': 'confusion', 'type': 'Disease', 'start': 662, 'end': 671, 'mesh': 'D003221'}, {'text': 'nausea', 'type': 'Disease', 'start': 677, 'end': 683, 'mesh': 'D009325'}, {'text': 'leukopenia', 'type': 'Disease', 'start': 701, 'end': 711, 'mesh': 'D007970'}, {'text': 'hematuria', 'type': 'Disease', 'start': 1046, 'end': 1055, 'mesh': 'D006417'}, {'text': 'Mesna', 'type': 'Chemical', 'start': 1142, 'end': 1147, 'mesh': 'D015080'}, {'text': 'hematuria', 'type': 'Disease', 'start': 1192, 'end': 1201, 'mesh': 'D006417'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 1240, 'end': 1250, 'mesh': 'D007069'}, {'text': 'Mesna', 'type': 'Chemical', 'start': 1304, 'end': 1309, 'mesh': 'D015080'}]"
+747,18161408,Myocardial infarction in pregnancy associated with clomiphene citrate for ovulation induction: a case report.,"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.","[{'text': 'Myocardial infarction', 'type': 'Disease', 'start': 0, 'end': 21, 'mesh': 'D009203'}, {'text': 'clomiphene citrate', 'type': 'Chemical', 'start': 51, 'end': 69, 'mesh': 'D002996'}, {'text': 'Clomiphene citrate', 'type': 'Chemical', 'start': 122, 'end': 140, 'mesh': 'D002996'}, {'text': 'CC', 'type': 'Chemical', 'start': 142, 'end': 144, 'mesh': 'D002996'}, {'text': 'Thromboembolism', 'type': 'Disease', 'start': 244, 'end': 259, 'mesh': 'D013923'}, {'text': 'CC', 'type': 'Chemical', 'start': 358, 'end': 360, 'mesh': 'D002996'}, {'text': 'coronary thrombosis', 'type': 'Disease', 'start': 374, 'end': 393, 'mesh': 'D003328'}, {'text': 'thromboembolism', 'type': 'Disease', 'start': 397, 'end': 412, 'mesh': 'D013923'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 495, 'end': 516, 'mesh': 'D009203'}, {'text': 'MI', 'type': 'Disease', 'start': 518, 'end': 520, 'mesh': 'D009203'}, {'text': 'CC', 'type': 'Chemical', 'start': 659, 'end': 661, 'mesh': 'D002996'}, {'text': 'chest pain', 'type': 'Disease', 'start': 705, 'end': 715, 'mesh': 'D002637'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 773, 'end': 794, 'mesh': 'D009203'}, {'text': 'radiation injury', 'type': 'Disease', 'start': 962, 'end': 978, 'mesh': 'D011832'}, {'text': 'CC', 'type': 'Chemical', 'start': 1192, 'end': 1194, 'mesh': 'D002996'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 1199, 'end': 1220, 'mesh': 'D009203'}, {'text': 'Thrombosis', 'type': 'Disease', 'start': 1222, 'end': 1232, 'mesh': 'D013927'}, {'text': 'CC', 'type': 'Chemical', 'start': 1279, 'end': 1281, 'mesh': 'D002996'}]"
+748,17574447,Hepatonecrosis and cholangitis related to long-term phenobarbital therapy: an autopsy report of two patients.,"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.","[{'text': 'Hepatonecrosis', 'type': 'Disease', 'start': 0, 'end': 14, 'mesh': '-1'}, {'text': 'cholangitis', 'type': 'Disease', 'start': 19, 'end': 30, 'mesh': 'D002761'}, {'text': 'phenobarbital', 'type': 'Chemical', 'start': 52, 'end': 65, 'mesh': 'D010634'}, {'text': 'Phenobarbital', 'type': 'Chemical', 'start': 110, 'end': 123, 'mesh': 'D010634'}, {'text': 'PB', 'type': 'Chemical', 'start': 125, 'end': 127, 'mesh': 'D010634'}, {'text': 'PB', 'type': 'Chemical', 'start': 191, 'end': 193, 'mesh': 'D010634'}, {'text': 'liver disease', 'type': 'Disease', 'start': 311, 'end': 324, 'mesh': 'D008107'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 386, 'end': 394, 'mesh': 'D004827'}, {'text': 'PB', 'type': 'Chemical', 'start': 408, 'end': 410, 'mesh': 'D010634'}, {'text': 'cardiac arrest', 'type': 'Disease', 'start': 452, 'end': 466, 'mesh': 'D006323'}, {'text': 'bronchopneumonia', 'type': 'Disease', 'start': 487, 'end': 503, 'mesh': 'D001996'}, {'text': 'necrosis', 'type': 'Disease', 'start': 680, 'end': 688, 'mesh': 'D009336'}, {'text': 'PB', 'type': 'Chemical', 'start': 868, 'end': 870, 'mesh': 'D010634'}, {'text': 'liver damage', 'type': 'Disease', 'start': 902, 'end': 914, 'mesh': 'D008107'}, {'text': 'PB', 'type': 'Chemical', 'start': 1071, 'end': 1073, 'mesh': 'D010634'}, {'text': 'chronic hepatic enzyme dysfunction', 'type': 'Disease', 'start': 1095, 'end': 1129, 'mesh': 'D056487'}]"
+749,16710500,Ethambutol-associated optic neuropathy.,"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.","[{'text': 'Ethambutol', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D004977'}, {'text': 'optic neuropathy', 'type': 'Disease', 'start': 22, 'end': 38, 'mesh': 'D009901'}, {'text': 'Ethambutol', 'type': 'Chemical', 'start': 54, 'end': 64, 'mesh': 'D004977'}, {'text': 'tuberculosis', 'type': 'Disease', 'start': 93, 'end': 105, 'mesh': 'D014376'}, {'text': 'visual loss', 'type': 'Disease', 'start': 188, 'end': 199, 'mesh': 'D014786'}, {'text': 'bitemporal hemianopia', 'type': 'Disease', 'start': 240, 'end': 261, 'mesh': 'D006423'}, {'text': 'ethambutol', 'type': 'Chemical', 'start': 301, 'end': 311, 'mesh': 'D004977'}, {'text': 'optic neuropathy', 'type': 'Disease', 'start': 329, 'end': 345, 'mesh': 'D009901'}, {'text': 'loss of central visual acuity, colour vision (Ishihara) and visual field', 'type': 'Disease', 'start': 380, 'end': 452, 'mesh': 'D014786'}, {'text': 'visual field loss', 'type': 'Disease', 'start': 458, 'end': 475, 'mesh': 'D014786'}, {'text': 'ethambutol', 'type': 'Chemical', 'start': 574, 'end': 584, 'mesh': 'D004977'}, {'text': 'loss of visual function', 'type': 'Disease', 'start': 838, 'end': 861, 'mesh': 'D014786'}, {'text': 'Ethambutol', 'type': 'Chemical', 'start': 876, 'end': 886, 'mesh': 'D004977'}, {'text': 'visual loss', 'type': 'Disease', 'start': 922, 'end': 933, 'mesh': 'D014786'}, {'text': 'ethambutol', 'type': 'Chemical', 'start': 1067, 'end': 1077, 'mesh': 'D004977'}, {'text': 'ethambutol', 'type': 'Chemical', 'start': 1103, 'end': 1113, 'mesh': 'D004977'}]"
+750,11694026,Tolerability of nimesulide and paracetamol in patients with NSAID-induced urticaria/angioedema.,"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 angioedema.","[{'text': 'nimesulide', 'type': 'Chemical', 'start': 16, 'end': 26, 'mesh': 'C012655'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 31, 'end': 42, 'mesh': 'D000082'}, {'text': 'NSAID', 'type': 'Chemical', 'start': 60, 'end': 65, 'mesh': 'D000894'}, {'text': 'urticaria', 'type': 'Disease', 'start': 74, 'end': 83, 'mesh': 'D014581'}, {'text': 'angioedema', 'type': 'Disease', 'start': 84, 'end': 94, 'mesh': 'D000799'}, {'text': 'nimesulide', 'type': 'Chemical', 'start': 140, 'end': 150, 'mesh': 'C012655'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 155, 'end': 166, 'mesh': 'D000082'}, {'text': 'nonsteroidal anti-inflammatory drugs', 'type': 'Chemical', 'start': 246, 'end': 282, 'mesh': 'D000894'}, {'text': 'NSAIDs', 'type': 'Chemical', 'start': 284, 'end': 290, 'mesh': 'D000894'}, {'text': 'nimesulide', 'type': 'Chemical', 'start': 355, 'end': 365, 'mesh': 'C012655'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 370, 'end': 381, 'mesh': 'D000082'}, {'text': 'NSAID', 'type': 'Chemical', 'start': 462, 'end': 467, 'mesh': 'D000894'}, {'text': 'urticaria', 'type': 'Disease', 'start': 476, 'end': 485, 'mesh': 'D014581'}, {'text': 'angioedema', 'type': 'Disease', 'start': 486, 'end': 496, 'mesh': 'D000799'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 600, 'end': 611, 'mesh': 'D000082'}, {'text': 'nimesulide', 'type': 'Chemical', 'start': 616, 'end': 626, 'mesh': 'C012655'}, {'text': 'nimesulide', 'type': 'Chemical', 'start': 686, 'end': 696, 'mesh': 'C012655'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 700, 'end': 711, 'mesh': 'D000082'}, {'text': 'NSAID', 'type': 'Chemical', 'start': 758, 'end': 763, 'mesh': 'D000894'}, {'text': 'urticaria', 'type': 'Disease', 'start': 772, 'end': 781, 'mesh': 'D014581'}, {'text': 'angioedema', 'type': 'Disease', 'start': 782, 'end': 792, 'mesh': 'D000799'}, {'text': 'nimesulide', 'type': 'Chemical', 'start': 853, 'end': 863, 'mesh': 'C012655'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 867, 'end': 878, 'mesh': 'D000082'}, {'text': 'nimesulide', 'type': 'Chemical', 'start': 912, 'end': 922, 'mesh': 'C012655'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 1011, 'end': 1022, 'mesh': 'D000082'}, {'text': 'urticaria', 'type': 'Disease', 'start': 1120, 'end': 1129, 'mesh': 'D014581'}, {'text': 'NSAID', 'type': 'Chemical', 'start': 1171, 'end': 1176, 'mesh': 'D000894'}, {'text': 'urticaria', 'type': 'Disease', 'start': 1185, 'end': 1194, 'mesh': 'D014581'}, {'text': 'angioedema', 'type': 'Disease', 'start': 1195, 'end': 1205, 'mesh': 'D000799'}, {'text': 'angioedema', 'type': 'Disease', 'start': 1209, 'end': 1219, 'mesh': 'D000799'}, {'text': 'urticaria', 'type': 'Disease', 'start': 1251, 'end': 1260, 'mesh': 'D014581'}, {'text': 'nimesulide', 'type': 'Chemical', 'start': 1371, 'end': 1381, 'mesh': 'C012655'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 1386, 'end': 1397, 'mesh': 'D000082'}, {'text': 'urticaria', 'type': 'Disease', 'start': 1426, 'end': 1435, 'mesh': 'D014581'}, {'text': 'angioedema', 'type': 'Disease', 'start': 1436, 'end': 1446, 'mesh': 'D000799'}, {'text': 'NSAIDs', 'type': 'Chemical', 'start': 1457, 'end': 1463, 'mesh': 'D000894'}, {'text': 'urticaria', 'type': 'Disease', 'start': 1579, 'end': 1588, 'mesh': 'D014581'}, {'text': 'NSAID', 'type': 'Chemical', 'start': 1621, 'end': 1626, 'mesh': 'D000894'}, {'text': 'angioedema', 'type': 'Disease', 'start': 1635, 'end': 1645, 'mesh': 'D000799'}]"
+751,11282081,Effects of verapamil on atrial fibrillation and its electrophysiological determinants in dogs.,"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.","[{'text': 'verapamil', 'type': 'Chemical', 'start': 11, 'end': 20, 'mesh': 'D014700'}, {'text': 'atrial fibrillation', 'type': 'Disease', 'start': 24, 'end': 43, 'mesh': 'D001281'}, {'text': 'Atrial tachycardia', 'type': 'Disease', 'start': 107, 'end': 125, 'mesh': 'D013617'}, {'text': 'atrial fibrillation', 'type': 'Disease', 'start': 188, 'end': 207, 'mesh': 'D001281'}, {'text': 'AF', 'type': 'Disease', 'start': 209, 'end': 211, 'mesh': 'D001281'}, {'text': 'Ca', 'type': 'Chemical', 'start': 234, 'end': 236, 'mesh': 'D002118'}, {'text': 'Ca', 'type': 'Chemical', 'start': 304, 'end': 306, 'mesh': 'D002118'}, {'text': 'AF', 'type': 'Disease', 'start': 339, 'end': 341, 'mesh': 'D001281'}, {'text': 'AF', 'type': 'Disease', 'start': 362, 'end': 364, 'mesh': 'D001281'}, {'text': 'Ca', 'type': 'Chemical', 'start': 385, 'end': 387, 'mesh': 'D002118'}, {'text': 'AF', 'type': 'Disease', 'start': 461, 'end': 463, 'mesh': 'D001281'}, {'text': 'Ca', 'type': 'Chemical', 'start': 477, 'end': 479, 'mesh': 'D002118'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 518, 'end': 527, 'mesh': 'D014700'}, {'text': 'morphine', 'type': 'Chemical', 'start': 531, 'end': 539, 'mesh': 'D009020'}, {'text': 'chloralose', 'type': 'Chemical', 'start': 540, 'end': 550, 'mesh': 'D002698'}, {'text': 'Diltiazem', 'type': 'Chemical', 'start': 570, 'end': 579, 'mesh': 'D004110'}, {'text': 'atropine', 'type': 'Chemical', 'start': 638, 'end': 646, 'mesh': 'D001285'}, {'text': 'nadolol', 'type': 'Chemical', 'start': 651, 'end': 658, 'mesh': 'D009248'}, {'text': 'AF', 'type': 'Disease', 'start': 781, 'end': 783, 'mesh': 'D001281'}, {'text': 'Verapamil', 'type': 'Chemical', 'start': 794, 'end': 803, 'mesh': 'D014700'}, {'text': 'AF', 'type': 'Disease', 'start': 811, 'end': 813, 'mesh': 'D001281'}, {'text': 'AF', 'type': 'Disease', 'start': 865, 'end': 867, 'mesh': 'D001281'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 1205, 'end': 1214, 'mesh': 'D014700'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 1238, 'end': 1247, 'mesh': 'D014700'}, {'text': 'AF', 'type': 'Disease', 'start': 1504, 'end': 1506, 'mesh': 'D001281'}, {'text': 'Diltiazem', 'type': 'Chemical', 'start': 1539, 'end': 1548, 'mesh': 'D004110'}, {'text': 'AF', 'type': 'Disease', 'start': 1569, 'end': 1571, 'mesh': 'D001281'}, {'text': 'AF', 'type': 'Disease', 'start': 1588, 'end': 1590, 'mesh': 'D001281'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 1664, 'end': 1673, 'mesh': 'D014700'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 1720, 'end': 1729, 'mesh': 'D014700'}, {'text': 'AF', 'type': 'Disease', 'start': 1748, 'end': 1750, 'mesh': 'D001281'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 1814, 'end': 1823, 'mesh': 'D014700'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 1828, 'end': 1837, 'mesh': 'D004110'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 1938, 'end': 1947, 'mesh': 'D014700'}, {'text': 'AF', 'type': 'Disease', 'start': 1957, 'end': 1959, 'mesh': 'D001281'}, {'text': 'Verapamil', 'type': 'Chemical', 'start': 2084, 'end': 2093, 'mesh': 'D014700'}, {'text': 'AF', 'type': 'Disease', 'start': 2103, 'end': 2105, 'mesh': 'D001281'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 2223, 'end': 2232, 'mesh': 'D004110'}]"
+752,10074612,"Hypotension, bradycardia, and asystole after high-dose intravenous methylprednisolone in a monitored patient.","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.","[{'text': 'Hypotension', 'type': 'Disease', 'start': 0, 'end': 11, 'mesh': 'D007022'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 13, 'end': 24, 'mesh': 'D001919'}, {'text': 'asystole', 'type': 'Disease', 'start': 30, 'end': 38, 'mesh': 'D006323'}, {'text': 'methylprednisolone', 'type': 'Chemical', 'start': 67, 'end': 85, 'mesh': 'D008775'}, {'text': 'hypotension', 'type': 'Disease', 'start': 130, 'end': 141, 'mesh': 'D007022'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 143, 'end': 154, 'mesh': 'D001919'}, {'text': 'asystole', 'type': 'Disease', 'start': 160, 'end': 168, 'mesh': 'D006323'}, {'text': 'methylprednisolone', 'type': 'Chemical', 'start': 215, 'end': 233, 'mesh': 'D008775'}, {'text': 'ischemic', 'type': 'Disease', 'start': 358, 'end': 366, 'mesh': 'D007511'}, {'text': 'cardiac disease', 'type': 'Disease', 'start': 367, 'end': 382, 'mesh': 'D006331'}, {'text': 'pulmonary-renal syndrome', 'type': 'Disease', 'start': 432, 'end': 456, 'mesh': 'C538458'}, {'text': 'hemoptysis', 'type': 'Disease', 'start': 462, 'end': 472, 'mesh': 'D006469'}, {'text': 'renal failure', 'type': 'Disease', 'start': 494, 'end': 507, 'mesh': 'D051437'}, {'text': 'hypoxemia', 'type': 'Disease', 'start': 513, 'end': 522, 'mesh': 'D000860'}, {'text': 'ventricular arrhythmia', 'type': 'Disease', 'start': 725, 'end': 747, 'mesh': 'D001145'}, {'text': 'sudden death', 'type': 'Disease', 'start': 803, 'end': 815, 'mesh': 'D003645'}, {'text': 'methylprednisolone', 'type': 'Chemical', 'start': 849, 'end': 867, 'mesh': 'D008775'}, {'text': 'IVMP', 'type': 'Chemical', 'start': 869, 'end': 873, 'mesh': 'D008775'}, {'text': 'cardiac disease', 'type': 'Disease', 'start': 1031, 'end': 1046, 'mesh': 'D006331'}, {'text': 'ventricular arrhythmia', 'type': 'Disease', 'start': 1127, 'end': 1149, 'mesh': 'D001145'}]"
+753,9209318,Lifetime treatment of mice with azidothymidine (AZT) produces myelodysplasia.,"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.","[{'text': 'azidothymidine', 'type': 'Chemical', 'start': 32, 'end': 46, 'mesh': 'D015215'}, {'text': 'AZT', 'type': 'Chemical', 'start': 48, 'end': 51, 'mesh': 'D015215'}, {'text': 'myelodysplasia', 'type': 'Disease', 'start': 62, 'end': 76, 'mesh': 'D009190'}, {'text': 'AZT', 'type': 'Chemical', 'start': 78, 'end': 81, 'mesh': 'D015215'}, {'text': 'macrocytic anemia', 'type': 'Disease', 'start': 96, 'end': 113, 'mesh': 'D000748'}, {'text': 'AIDS', 'type': 'Disease', 'start': 117, 'end': 121, 'mesh': 'D000163'}, {'text': 'AZT', 'type': 'Chemical', 'start': 144, 'end': 147, 'mesh': 'D015215'}, {'text': 'AZT', 'type': 'Chemical', 'start': 232, 'end': 235, 'mesh': 'D015215'}, {'text': 'thymidine', 'type': 'Chemical', 'start': 263, 'end': 272, 'mesh': 'D013936'}, {'text': 'phosphate', 'type': 'Chemical', 'start': 293, 'end': 302, 'mesh': 'D010710'}, {'text': 'AZT', 'type': 'Chemical', 'start': 454, 'end': 457, 'mesh': 'D015215'}, {'text': 'AZT', 'type': 'Chemical', 'start': 596, 'end': 599, 'mesh': 'D015215'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 791, 'end': 807, 'mesh': 'D013921'}, {'text': 'myelodysplastic syndrome', 'type': 'Disease', 'start': 839, 'end': 863, 'mesh': 'D009190'}, {'text': 'MDS', 'type': 'Disease', 'start': 865, 'end': 868, 'mesh': 'D009190'}, {'text': 'myelodysplasia', 'type': 'Disease', 'start': 957, 'end': 971, 'mesh': 'D009190'}, {'text': 'myelodysplastic', 'type': 'Disease', 'start': 1001, 'end': 1016, 'mesh': 'D009190'}, {'text': 'hyperplastic marrow', 'type': 'Disease', 'start': 1171, 'end': 1190, 'mesh': 'D001855'}, {'text': 'dysmyelopoiesis', 'type': 'Disease', 'start': 1192, 'end': 1207, 'mesh': 'D009190'}, {'text': 'hypocellular marrow', 'type': 'Disease', 'start': 1214, 'end': 1233, 'mesh': 'D001855'}, {'text': 'myelodysplasia', 'type': 'Disease', 'start': 1251, 'end': 1265, 'mesh': 'D009190'}, {'text': 'dyserythropoiesis', 'type': 'Disease', 'start': 1271, 'end': 1288, 'mesh': '-1'}, {'text': 'hemosiderosis', 'type': 'Disease', 'start': 1290, 'end': 1303, 'mesh': 'D006486'}, {'text': 'hypocellular marrow', 'type': 'Disease', 'start': 1310, 'end': 1329, 'mesh': 'D001855'}, {'text': 'AZT', 'type': 'Chemical', 'start': 1347, 'end': 1350, 'mesh': 'D015215'}, {'text': 'myelodysplastic syndrome', 'type': 'Disease', 'start': 1498, 'end': 1522, 'mesh': 'D009190'}]"
+754,8742498,Influence of diet free of NAD-precursors on acetaminophen hepatotoxicity in mice.,"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.","[{'text': 'NAD', 'type': 'Chemical', 'start': 26, 'end': 29, 'mesh': 'D009243'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 44, 'end': 57, 'mesh': 'D000082'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 58, 'end': 72, 'mesh': 'D056486'}, {'text': 'nicotinic acid amide', 'type': 'Chemical', 'start': 140, 'end': 160, 'mesh': 'D009536'}, {'text': 'poly(ADP-ribose)', 'type': 'Chemical', 'start': 187, 'end': 203, 'mesh': 'D011064'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 258, 'end': 271, 'mesh': 'D000082'}, {'text': 'AAP', 'type': 'Chemical', 'start': 273, 'end': 276, 'mesh': 'D000082'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 278, 'end': 287, 'mesh': 'D056486'}, {'text': 'AAP', 'type': 'Chemical', 'start': 309, 'end': 312, 'mesh': 'D000082'}, {'text': 'liver injury', 'type': 'Disease', 'start': 321, 'end': 333, 'mesh': 'D056486'}, {'text': 'NAD', 'type': 'Chemical', 'start': 461, 'end': 464, 'mesh': 'D009243'}, {'text': 'AAP', 'type': 'Chemical', 'start': 525, 'end': 528, 'mesh': 'D000082'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 529, 'end': 538, 'mesh': 'D056486'}, {'text': 'ethanol', 'type': 'Chemical', 'start': 583, 'end': 590, 'mesh': 'D000431'}, {'text': 'Liver injuries', 'type': 'Disease', 'start': 621, 'end': 635, 'mesh': 'D056486'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 675, 'end': 684, 'mesh': 'D018698'}, {'text': 'oxaloacetate', 'type': 'Chemical', 'start': 685, 'end': 697, 'mesh': 'D062907'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 721, 'end': 730, 'mesh': 'D018698'}, {'text': 'pyruvate', 'type': 'Chemical', 'start': 731, 'end': 739, 'mesh': 'D019289'}, {'text': 'AAP', 'type': 'Chemical', 'start': 766, 'end': 769, 'mesh': 'D000082'}, {'text': 'ethanol', 'type': 'Chemical', 'start': 914, 'end': 921, 'mesh': 'D000431'}, {'text': 'nicotinic acid amide', 'type': 'Chemical', 'start': 939, 'end': 959, 'mesh': 'D009536'}, {'text': 'NAA', 'type': 'Chemical', 'start': 961, 'end': 964, 'mesh': 'D009536'}, {'text': 'NAD', 'type': 'Chemical', 'start': 1038, 'end': 1041, 'mesh': 'D009243'}, {'text': 'AAP', 'type': 'Chemical', 'start': 1148, 'end': 1151, 'mesh': 'D000082'}, {'text': 'ethanol', 'type': 'Chemical', 'start': 1191, 'end': 1198, 'mesh': 'D000431'}, {'text': 'liver damage', 'type': 'Disease', 'start': 1231, 'end': 1243, 'mesh': 'D056486'}, {'text': 'ethanol', 'type': 'Chemical', 'start': 1268, 'end': 1275, 'mesh': 'D000431'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 1304, 'end': 1313, 'mesh': 'D056486'}, {'text': 'NAA', 'type': 'Chemical', 'start': 1333, 'end': 1336, 'mesh': 'D009536'}, {'text': 'ethanol', 'type': 'Chemical', 'start': 1350, 'end': 1357, 'mesh': 'D000431'}, {'text': 'AAP', 'type': 'Chemical', 'start': 1358, 'end': 1361, 'mesh': 'D000082'}, {'text': 'AAP', 'type': 'Chemical', 'start': 1406, 'end': 1409, 'mesh': 'D000082'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 1418, 'end': 1427, 'mesh': 'D056486'}, {'text': 'ethanol', 'type': 'Chemical', 'start': 1452, 'end': 1459, 'mesh': 'D000431'}, {'text': 'NAA', 'type': 'Chemical', 'start': 1519, 'end': 1522, 'mesh': 'D009536'}, {'text': 'NAD', 'type': 'Chemical', 'start': 1573, 'end': 1576, 'mesh': 'D009243'}, {'text': 'NAA', 'type': 'Chemical', 'start': 1609, 'end': 1612, 'mesh': 'D009536'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 1676, 'end': 1689, 'mesh': 'D000082'}, {'text': 'hepatic damage', 'type': 'Disease', 'start': 1708, 'end': 1722, 'mesh': 'D056486'}]"
+755,2435991,Antiarrhythmic plasma concentrations of cibenzoline on canine ventricular arrhythmias.,"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.","[{'text': 'cibenzoline', 'type': 'Chemical', 'start': 40, 'end': 51, 'mesh': 'C032151'}, {'text': 'ventricular arrhythmias', 'type': 'Disease', 'start': 62, 'end': 85, 'mesh': 'D001145'}, {'text': 'digitalis', 'type': 'Chemical', 'start': 123, 'end': 132, 'mesh': 'D004071'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 139, 'end': 149, 'mesh': 'D004837'}, {'text': 'ventricular arrhythmias', 'type': 'Disease', 'start': 165, 'end': 188, 'mesh': 'D001145'}, {'text': 'cibenzoline', 'type': 'Chemical', 'start': 216, 'end': 227, 'mesh': 'C032151'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 298, 'end': 308, 'mesh': 'D001145'}, {'text': 'Cibenzoline', 'type': 'Chemical', 'start': 331, 'end': 342, 'mesh': 'C032151'}, {'text': 'arrhythmias', 'type': 'Disease', 'start': 362, 'end': 373, 'mesh': 'D001145'}, {'text': 'arrhythmias', 'type': 'Disease', 'start': 427, 'end': 438, 'mesh': 'D001145'}, {'text': 'digitalis', 'type': 'Chemical', 'start': 498, 'end': 507, 'mesh': 'D004071'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 513, 'end': 523, 'mesh': 'D004837'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 731, 'end': 741, 'mesh': 'D004837'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 750, 'end': 760, 'mesh': 'D001145'}, {'text': 'arrhythmias', 'type': 'Disease', 'start': 820, 'end': 831, 'mesh': 'D001145'}, {'text': 'mexiletine', 'type': 'Chemical', 'start': 885, 'end': 895, 'mesh': 'D008801'}, {'text': 'tocainide', 'type': 'Chemical', 'start': 900, 'end': 909, 'mesh': 'D016677'}, {'text': 'cibenzoline', 'type': 'Chemical', 'start': 991, 'end': 1002, 'mesh': 'C032151'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 1017, 'end': 1028, 'mesh': 'D007022'}, {'text': 'depressive', 'type': 'Disease', 'start': 1044, 'end': 1054, 'mesh': 'D003866'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 1129, 'end': 1139, 'mesh': 'D001145'}]"
+756,950631,Immunopathology of penicillamine-induced glomerular disease.,"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.","[{'text': 'penicillamine', 'type': 'Chemical', 'start': 19, 'end': 32, 'mesh': 'D010396'}, {'text': 'glomerular disease', 'type': 'Disease', 'start': 41, 'end': 59, 'mesh': 'D007674'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 80, 'end': 100, 'mesh': 'D001172'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 117, 'end': 128, 'mesh': 'D011507'}, {'text': 'D-penicillamine', 'type': 'Chemical', 'start': 171, 'end': 186, 'mesh': 'D010396'}, {'text': 'membranous glomerulonephritis', 'type': 'Disease', 'start': 642, 'end': 671, 'mesh': 'D015433'}]"
+757,663266,Ventricular fibrillation from diatrizoate with and without chelating agents.,"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.","[{'text': 'Ventricular fibrillation', 'type': 'Disease', 'start': 0, 'end': 24, 'mesh': 'D014693'}, {'text': 'diatrizoate', 'type': 'Chemical', 'start': 30, 'end': 41, 'mesh': 'D003973'}, {'text': 'toxicity', 'type': 'Disease', 'start': 81, 'end': 89, 'mesh': 'D064420'}, {'text': 'Renografin 76%', 'type': 'Chemical', 'start': 93, 'end': 107, 'mesh': 'C027278'}, {'text': 'Hypaque 76%', 'type': 'Chemical', 'start': 134, 'end': 145, 'mesh': 'C027278'}, {'text': 'Renografin', 'type': 'Chemical', 'start': 217, 'end': 227, 'mesh': 'D003974'}, {'text': 'sodium citrate', 'type': 'Chemical', 'start': 258, 'end': 272, 'mesh': 'C102006'}, {'text': 'disodium edetate', 'type': 'Chemical', 'start': 277, 'end': 293, 'mesh': 'D004492'}, {'text': 'Hypaque', 'type': 'Chemical', 'start': 301, 'end': 308, 'mesh': 'D003973'}, {'text': 'calcium disodium edetate', 'type': 'Chemical', 'start': 318, 'end': 342, 'mesh': 'D004492'}, {'text': 'sodium citrate', 'type': 'Chemical', 'start': 350, 'end': 364, 'mesh': 'C102006'}, {'text': 'Ventricular fibrillation', 'type': 'Disease', 'start': 366, 'end': 390, 'mesh': 'D014693'}, {'text': 'Renografin', 'type': 'Chemical', 'start': 430, 'end': 440, 'mesh': 'D003974'}, {'text': 'toxicity', 'type': 'Disease', 'start': 489, 'end': 497, 'mesh': 'D064420'}]"
+758,19319147,Rapid reversal of anticoagulation reduces hemorrhage volume in a mouse model of warfarin-associated intracerebral hemorrhage.,"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.","[{'text': 'hemorrhage', 'type': 'Disease', 'start': 42, 'end': 52, 'mesh': 'D006470'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 80, 'end': 88, 'mesh': 'D014859'}, {'text': 'intracerebral hemorrhage', 'type': 'Disease', 'start': 100, 'end': 124, 'mesh': 'D002543'}, {'text': 'Warfarin', 'type': 'Chemical', 'start': 126, 'end': 134, 'mesh': 'D014859'}, {'text': 'intracerebral hemorrhage', 'type': 'Disease', 'start': 146, 'end': 170, 'mesh': 'D002543'}, {'text': 'ICH', 'type': 'Disease', 'start': 174, 'end': 177, 'mesh': 'D002543'}, {'text': 'stroke', 'type': 'Disease', 'start': 199, 'end': 205, 'mesh': 'D020521'}, {'text': 'ICH', 'type': 'Disease', 'start': 260, 'end': 263, 'mesh': 'D002543'}, {'text': 'prothrombin complex concentrate', 'type': 'Chemical', 'start': 354, 'end': 385, 'mesh': 'C025667'}, {'text': 'PCC', 'type': 'Chemical', 'start': 387, 'end': 390, 'mesh': 'C025667'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 462, 'end': 470, 'mesh': 'D014859'}, {'text': 'PCC', 'type': 'Chemical', 'start': 628, 'end': 631, 'mesh': 'C025667'}, {'text': 'hemorrhage', 'type': 'Disease', 'start': 749, 'end': 759, 'mesh': 'D006470'}, {'text': 'PCC', 'type': 'Chemical', 'start': 848, 'end': 851, 'mesh': 'C025667'}, {'text': 'hemorrhage', 'type': 'Disease', 'start': 920, 'end': 930, 'mesh': 'D006470'}, {'text': 'PCC', 'type': 'Chemical', 'start': 1069, 'end': 1072, 'mesh': 'C025667'}, {'text': 'hematomas', 'type': 'Disease', 'start': 1222, 'end': 1231, 'mesh': 'D006406'}, {'text': 'PCC', 'type': 'Chemical', 'start': 1312, 'end': 1315, 'mesh': 'C025667'}, {'text': 'PCC', 'type': 'Chemical', 'start': 1363, 'end': 1366, 'mesh': 'C025667'}, {'text': 'ICH', 'type': 'Disease', 'start': 1408, 'end': 1411, 'mesh': 'D002543'}, {'text': 'ICH', 'type': 'Disease', 'start': 1559, 'end': 1562, 'mesh': 'D002543'}]"
+759,16634859,Impact of alcohol exposure after pregnancy recognition on ultrasonographic fetal growth measures.,"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.","[{'text': 'alcohol', 'type': 'Chemical', 'start': 10, 'end': 17, 'mesh': 'D000431'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 197, 'end': 204, 'mesh': 'D000431'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 340, 'end': 347, 'mesh': 'D000431'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 470, 'end': 477, 'mesh': 'D000431'}, {'text': 'growth impairment', 'type': 'Disease', 'start': 492, 'end': 509, 'mesh': 'D006130'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 660, 'end': 667, 'mesh': 'D000431'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 893, 'end': 900, 'mesh': 'D000431'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 1045, 'end': 1052, 'mesh': 'D000431'}, {'text': 'drug abuse', 'type': 'Disease', 'start': 1395, 'end': 1405, 'mesh': 'D019966'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 1630, 'end': 1637, 'mesh': 'D000431'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 1696, 'end': 1703, 'mesh': 'D000431'}, {'text': 'reduced cerebellar growth', 'type': 'Disease', 'start': 1779, 'end': 1804, 'mesh': 'D006130'}, {'text': 'decreased cranial to body growth', 'type': 'Disease', 'start': 1816, 'end': 1848, 'mesh': 'D006130'}, {'text': 'Amphetamine', 'type': 'Chemical', 'start': 1924, 'end': 1935, 'mesh': 'D000661'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 2378, 'end': 2385, 'mesh': 'D000431'}]"
+760,16471092,Urinary symptoms and quality of life changes in Thai women with overactive bladder after tolterodine treatment.,"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.","[{'text': 'overactive bladder', 'type': 'Disease', 'start': 64, 'end': 82, 'mesh': 'D053201'}, {'text': 'tolterodine', 'type': 'Chemical', 'start': 89, 'end': 100, 'mesh': 'C099041'}, {'text': 'overactive bladder', 'type': 'Disease', 'start': 201, 'end': 219, 'mesh': 'D053201'}, {'text': 'OAB', 'type': 'Disease', 'start': 221, 'end': 224, 'mesh': 'D053201'}, {'text': 'tolterodine', 'type': 'Chemical', 'start': 232, 'end': 243, 'mesh': 'C099041'}, {'text': 'OAB', 'type': 'Disease', 'start': 328, 'end': 331, 'mesh': 'D053201'}, {'text': 'Tolterodine', 'type': 'Chemical', 'start': 458, 'end': 469, 'mesh': 'C099041'}, {'text': 'nocturia', 'type': 'Disease', 'start': 817, 'end': 825, 'mesh': 'D053158'}, {'text': 'dry month', 'type': 'Disease', 'start': 926, 'end': 935, 'mesh': 'D014987'}, {'text': 'dry mouth', 'type': 'Disease', 'start': 1096, 'end': 1105, 'mesh': 'D014987'}, {'text': 'Tolterodine', 'type': 'Chemical', 'start': 1257, 'end': 1268, 'mesh': 'C099041'}, {'text': 'OAB', 'type': 'Disease', 'start': 1352, 'end': 1355, 'mesh': 'D053201'}]"
+761,16174948,Absence of acute cerebral vasoconstriction after cocaine-associated subarachnoid hemorrhage.,"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.","[{'text': 'cocaine', 'type': 'Chemical', 'start': 49, 'end': 56, 'mesh': 'D003042'}, {'text': 'subarachnoid hemorrhage', 'type': 'Disease', 'start': 68, 'end': 91, 'mesh': 'D013345'}, {'text': 'Cocaine', 'type': 'Chemical', 'start': 107, 'end': 114, 'mesh': 'D003042'}, {'text': 'neurovascular complications', 'type': 'Disease', 'start': 144, 'end': 171, 'mesh': 'D013901'}, {'text': 'vasculitis', 'type': 'Disease', 'start': 213, 'end': 223, 'mesh': 'D014657'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 283, 'end': 290, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 399, 'end': 406, 'mesh': 'D003042'}, {'text': 'subarachnoid hemorrhage', 'type': 'Disease', 'start': 418, 'end': 441, 'mesh': 'D013345'}, {'text': 'SAH', 'type': 'Disease', 'start': 443, 'end': 446, 'mesh': 'D013345'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 488, 'end': 495, 'mesh': 'D003042'}, {'text': 'SAH', 'type': 'Disease', 'start': 536, 'end': 539, 'mesh': 'D013345'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 612, 'end': 619, 'mesh': 'D003042'}, {'text': 'SAH', 'type': 'Disease', 'start': 775, 'end': 778, 'mesh': 'D013345'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 951, 'end': 958, 'mesh': 'D003042'}, {'text': 'vasculitis', 'type': 'Disease', 'start': 1881, 'end': 1891, 'mesh': 'D014657'}, {'text': 'aneurysmal', 'type': 'Disease', 'start': 1951, 'end': 1961, 'mesh': 'D017542'}, {'text': 'SAH', 'type': 'Disease', 'start': 1962, 'end': 1965, 'mesh': 'D013345'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1982, 'end': 1989, 'mesh': 'D003042'}]"
+762,15042318,Atrial fibrillation following chemotherapy for stage IIIE diffuse large B-cell gastric lymphoma in a patient with myotonic dystrophy (Steinert's disease).,"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.","[{'text': 'Atrial fibrillation', 'type': 'Disease', 'start': 0, 'end': 19, 'mesh': 'D001281'}, {'text': 'gastric lymphoma', 'type': 'Disease', 'start': 79, 'end': 95, 'mesh': 'C535648'}, {'text': 'myotonic dystrophy', 'type': 'Disease', 'start': 114, 'end': 132, 'mesh': 'D009223'}, {'text': ""Steinert's disease"", 'type': 'Disease', 'start': 134, 'end': 152, 'mesh': 'D009223'}, {'text': 'gastric lymphoma', 'type': 'Disease', 'start': 223, 'end': 239, 'mesh': 'C535648'}, {'text': 'myotonic dystrophy', 'type': 'Disease', 'start': 244, 'end': 262, 'mesh': 'D009223'}, {'text': 'muscular dystrophy', 'type': 'Disease', 'start': 294, 'end': 312, 'mesh': 'D009136'}, {'text': 'atrial fibrillation', 'type': 'Disease', 'start': 325, 'end': 344, 'mesh': 'D001281'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 368, 'end': 379, 'mesh': 'D004317'}, {'text': 'Atrial fibrillation', 'type': 'Disease', 'start': 420, 'end': 439, 'mesh': 'D001281'}, {'text': 'cardiac arrhythmias', 'type': 'Disease', 'start': 449, 'end': 468, 'mesh': 'D001145'}, {'text': 'cardiac toxicity', 'type': 'Disease', 'start': 538, 'end': 554, 'mesh': 'D066126'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 668, 'end': 678, 'mesh': 'D001145'}]"
+763,12448656,A phase II study of thalidomide in advanced metastatic renal cell carcinoma.,"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.","[{'text': 'thalidomide', 'type': 'Chemical', 'start': 20, 'end': 31, 'mesh': 'D013792'}, {'text': 'renal cell carcinoma', 'type': 'Disease', 'start': 55, 'end': 75, 'mesh': 'D002292'}, {'text': 'toxicity', 'type': 'Disease', 'start': 105, 'end': 113, 'mesh': 'D064420'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 130, 'end': 141, 'mesh': 'D013792'}, {'text': 'renal cell cancer', 'type': 'Disease', 'start': 179, 'end': 196, 'mesh': 'D002292'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 368, 'end': 379, 'mesh': 'D013792'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 444, 'end': 455, 'mesh': 'D013792'}, {'text': 'metastases', 'type': 'Disease', 'start': 848, 'end': 858, 'mesh': 'D009362'}, {'text': 'Somnolence', 'type': 'Disease', 'start': 926, 'end': 936, 'mesh': 'D006970'}, {'text': 'constipation', 'type': 'Disease', 'start': 941, 'end': 953, 'mesh': 'D003248'}, {'text': 'toxicities', 'type': 'Disease', 'start': 969, 'end': 979, 'mesh': 'D064420'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 1178, 'end': 1189, 'mesh': 'D013792'}, {'text': 'renal cell carcinoma', 'type': 'Disease', 'start': 1193, 'end': 1213, 'mesh': 'D002292'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 1387, 'end': 1398, 'mesh': 'D013792'}, {'text': 'renal cell carcinoma', 'type': 'Disease', 'start': 1403, 'end': 1423, 'mesh': 'D002292'}]"
+764,12231232,"The striatum as a target for anti-rigor effects of an antagonist of mGluR1, but not an agonist of group II metabotropic glutamate receptors.","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.","[{'text': 'glutamate', 'type': 'Chemical', 'start': 120, 'end': 129, 'mesh': 'D018698'}, {'text': 'Haloperidol', 'type': 'Chemical', 'start': 334, 'end': 345, 'mesh': 'D006220'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 367, 'end': 379, 'mesh': 'D010300'}, {'text': 'muscle rigidity', 'type': 'Disease', 'start': 385, 'end': 400, 'mesh': 'D009127'}, {'text': '(RS)-1-aminoindan-1,5-dicarboxylic acid', 'type': 'Chemical', 'start': 512, 'end': 551, 'mesh': 'C095756'}, {'text': 'AIDA', 'type': 'Chemical', 'start': 553, 'end': 557, 'mesh': 'C095756'}, {'text': '(2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate', 'type': 'Chemical', 'start': 631, 'end': 675, 'mesh': 'C097299'}, {'text': '2R,4R-APDC', 'type': 'Chemical', 'start': 677, 'end': 687, 'mesh': 'C097299'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 792, 'end': 803, 'mesh': 'D006220'}, {'text': 'AIDA', 'type': 'Chemical', 'start': 821, 'end': 825, 'mesh': 'C095756'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 878, 'end': 889, 'mesh': 'D006220'}, {'text': 'muscle rigidity', 'type': 'Disease', 'start': 898, 'end': 913, 'mesh': 'D009127'}, {'text': '2R,4R-APDC', 'type': 'Chemical', 'start': 928, 'end': 938, 'mesh': 'C097299'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 1097, 'end': 1109, 'mesh': 'D010300'}, {'text': 'muscle rigidity', 'type': 'Disease', 'start': 1110, 'end': 1125, 'mesh': 'D009127'}]"
+765,11847945,Acute cholestatic hepatitis after exposure to isoflurane.,"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.","[{'text': 'isoflurane', 'type': 'Chemical', 'start': 46, 'end': 56, 'mesh': 'D007530'}, {'text': 'isoflurane', 'type': 'Chemical', 'start': 167, 'end': 177, 'mesh': 'D007530'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 414, 'end': 423, 'mesh': 'D056486'}, {'text': 'dipyrone', 'type': 'Chemical', 'start': 471, 'end': 479, 'mesh': 'D004177'}, {'text': 'analgesia', 'type': 'Disease', 'start': 484, 'end': 493, 'mesh': 'D000699'}, {'text': 'alanine', 'type': 'Chemical', 'start': 499, 'end': 506, 'mesh': 'D000409'}, {'text': 'bilirubin', 'type': 'Chemical', 'start': 587, 'end': 596, 'mesh': 'D001663'}, {'text': 'dipyrone', 'type': 'Chemical', 'start': 709, 'end': 717, 'mesh': 'D004177'}, {'text': 'halothane hepatitis', 'type': 'Disease', 'start': 805, 'end': 824, 'mesh': 'C562477'}, {'text': 'Isoflurane', 'type': 'Chemical', 'start': 879, 'end': 889, 'mesh': 'D007530'}]"
+766,11284996,Calcitonin gene-related peptide levels during nitric oxide-induced headache in patients with chronic tension-type headache.,"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.","[{'text': 'nitric oxide', 'type': 'Chemical', 'start': 46, 'end': 58, 'mesh': 'D009569'}, {'text': 'headache', 'type': 'Disease', 'start': 67, 'end': 75, 'mesh': 'D006261'}, {'text': 'tension-type headache', 'type': 'Disease', 'start': 101, 'end': 122, 'mesh': 'D018781'}, {'text': 'nitric oxide', 'type': 'Chemical', 'start': 150, 'end': 162, 'mesh': 'D009569'}, {'text': 'NO', 'type': 'Chemical', 'start': 164, 'end': 166, 'mesh': 'D009569'}, {'text': 'headache', 'type': 'Disease', 'start': 176, 'end': 184, 'mesh': 'D006261'}, {'text': 'primary headaches', 'type': 'Disease', 'start': 188, 'end': 205, 'mesh': 'D051270'}, {'text': 'headache', 'type': 'Disease', 'start': 354, 'end': 362, 'mesh': 'D006261'}, {'text': 'NO', 'type': 'Chemical', 'start': 378, 'end': 380, 'mesh': 'D009569'}, {'text': 'glyceryl trinitrate', 'type': 'Chemical', 'start': 387, 'end': 406, 'mesh': 'D005996'}, {'text': 'GTN', 'type': 'Chemical', 'start': 408, 'end': 411, 'mesh': 'D005996'}, {'text': 'tension-type headache', 'type': 'Disease', 'start': 441, 'end': 462, 'mesh': 'D018781'}, {'text': 'GTN', 'type': 'Chemical', 'start': 554, 'end': 557, 'mesh': 'D005996'}, {'text': 'headache', 'type': 'Disease', 'start': 588, 'end': 596, 'mesh': 'D006261'}, {'text': 'headache', 'type': 'Disease', 'start': 763, 'end': 771, 'mesh': 'D006261'}, {'text': 'GTN', 'type': 'Chemical', 'start': 779, 'end': 782, 'mesh': 'D005996'}, {'text': 'headache', 'type': 'Disease', 'start': 819, 'end': 827, 'mesh': 'D006261'}, {'text': 'GTN', 'type': 'Chemical', 'start': 967, 'end': 970, 'mesh': 'D005996'}, {'text': 'GTN', 'type': 'Chemical', 'start': 1065, 'end': 1068, 'mesh': 'D005996'}, {'text': 'GTN', 'type': 'Chemical', 'start': 1216, 'end': 1219, 'mesh': 'D005996'}, {'text': 'NO', 'type': 'Chemical', 'start': 1282, 'end': 1284, 'mesh': 'D009569'}, {'text': 'headache', 'type': 'Disease', 'start': 1303, 'end': 1311, 'mesh': 'D006261'}]"
+767,11078231,Myocardial ischemia due to coronary artery spasm during dobutamine stress echocardiography.,"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.","[{'text': 'Myocardial ischemia', 'type': 'Disease', 'start': 0, 'end': 19, 'mesh': 'D017202'}, {'text': 'coronary artery spasm', 'type': 'Disease', 'start': 27, 'end': 48, 'mesh': 'D003329'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 56, 'end': 66, 'mesh': 'D004280'}, {'text': 'Dobutamine', 'type': 'Chemical', 'start': 92, 'end': 102, 'mesh': 'D004280'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 175, 'end': 194, 'mesh': 'D017202'}, {'text': 'coronary artery stenosis', 'type': 'Disease', 'start': 349, 'end': 373, 'mesh': 'D023921'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 426, 'end': 445, 'mesh': 'D017202'}, {'text': 'coronary spasm', 'type': 'Disease', 'start': 453, 'end': 467, 'mesh': 'D003329'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 482, 'end': 492, 'mesh': 'D004280'}, {'text': 'coronary spastic angina', 'type': 'Disease', 'start': 531, 'end': 554, 'mesh': 'D000788'}, {'text': 'coronary artery stenosis', 'type': 'Disease', 'start': 585, 'end': 609, 'mesh': 'D023921'}, {'text': 'anginal', 'type': 'Disease', 'start': 628, 'end': 635, 'mesh': 'D000787'}, {'text': 'variant angina', 'type': 'Disease', 'start': 696, 'end': 710, 'mesh': 'D000788'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 770, 'end': 783, 'mesh': 'D000109'}, {'text': 'coronary artery stenosis', 'type': 'Disease', 'start': 798, 'end': 822, 'mesh': 'D023921'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 904, 'end': 914, 'mesh': 'D004280'}, {'text': 'chest pain', 'type': 'Disease', 'start': 1099, 'end': 1109, 'mesh': 'D002637'}, {'text': 'chest pain', 'type': 'Disease', 'start': 1136, 'end': 1146, 'mesh': 'D002637'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 1236, 'end': 1246, 'mesh': 'D004280'}, {'text': 'coronary spasm', 'type': 'Disease', 'start': 1259, 'end': 1273, 'mesh': 'D003329'}, {'text': 'coronary spastic angina', 'type': 'Disease', 'start': 1296, 'end': 1319, 'mesh': 'D000788'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 1355, 'end': 1378, 'mesh': 'D003324'}, {'text': 'coronary stenosis', 'type': 'Disease', 'start': 1395, 'end': 1412, 'mesh': 'D023921'}, {'text': 'coronary spasm', 'type': 'Disease', 'start': 1423, 'end': 1437, 'mesh': 'D003329'}]"
+768,10523326,Nitric oxide synthase expression in the course of lead-induced hypertension.,"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.","[{'text': 'Nitric oxide', 'type': 'Chemical', 'start': 0, 'end': 12, 'mesh': 'D009569'}, {'text': 'lead', 'type': 'Chemical', 'start': 50, 'end': 54, 'mesh': 'D007854'}, {'text': 'hypertension', 'type': 'Disease', 'start': 63, 'end': 75, 'mesh': 'D006973'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 114, 'end': 120, 'mesh': 'D010100'}, {'text': 'NO', 'type': 'Chemical', 'start': 165, 'end': 167, 'mesh': 'D009569'}, {'text': 'NO', 'type': 'Chemical', 'start': 201, 'end': 203, 'mesh': 'D009569'}, {'text': 'nitrotyrosine', 'type': 'Chemical', 'start': 221, 'end': 234, 'mesh': 'C002744'}, {'text': 'lead', 'type': 'Chemical', 'start': 267, 'end': 271, 'mesh': 'D007854'}, {'text': 'hypertension', 'type': 'Disease', 'start': 280, 'end': 292, 'mesh': 'D006973'}, {'text': 'lead', 'type': 'Chemical', 'start': 369, 'end': 373, 'mesh': 'D007854'}, {'text': 'hypertension', 'type': 'Disease', 'start': 382, 'end': 394, 'mesh': 'D006973'}, {'text': 'NO', 'type': 'Chemical', 'start': 425, 'end': 427, 'mesh': 'D009569'}, {'text': 'lead', 'type': 'Chemical', 'start': 508, 'end': 512, 'mesh': 'D007854'}, {'text': 'lead acetate', 'type': 'Chemical', 'start': 534, 'end': 546, 'mesh': 'C008261'}, {'text': 'lead', 'type': 'Chemical', 'start': 612, 'end': 616, 'mesh': 'D007854'}, {'text': 'vitamin E', 'type': 'Chemical', 'start': 621, 'end': 630, 'mesh': 'D014810'}, {'text': 'vitamin E', 'type': 'Chemical', 'start': 712, 'end': 721, 'mesh': 'D014810'}, {'text': 'malondialdehyde', 'type': 'Chemical', 'start': 802, 'end': 817, 'mesh': 'D008315'}, {'text': 'MDA', 'type': 'Chemical', 'start': 819, 'end': 822, 'mesh': 'D008315'}, {'text': 'lead', 'type': 'Chemical', 'start': 927, 'end': 931, 'mesh': 'D007854'}, {'text': 'MDA', 'type': 'Chemical', 'start': 992, 'end': 995, 'mesh': 'D008315'}, {'text': 'Vitamin E', 'type': 'Chemical', 'start': 1122, 'end': 1131, 'mesh': 'D014810'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1160, 'end': 1172, 'mesh': 'D006973'}, {'text': 'MDA', 'type': 'Chemical', 'start': 1189, 'end': 1192, 'mesh': 'D008315'}, {'text': 'Vitamin E', 'type': 'Chemical', 'start': 1328, 'end': 1337, 'mesh': 'D014810'}, {'text': 'MDA', 'type': 'Chemical', 'start': 1401, 'end': 1404, 'mesh': 'D008315'}, {'text': 'lead', 'type': 'Chemical', 'start': 1522, 'end': 1526, 'mesh': 'D007854'}, {'text': 'lead', 'type': 'Chemical', 'start': 1569, 'end': 1573, 'mesh': 'D007854'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1582, 'end': 1594, 'mesh': 'D006973'}, {'text': 'NO', 'type': 'Chemical', 'start': 1743, 'end': 1745, 'mesh': 'D009569'}, {'text': 'lead', 'type': 'Chemical', 'start': 1760, 'end': 1764, 'mesh': 'D007854'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1878, 'end': 1890, 'mesh': 'D006973'}]"
+769,9867728,Risk for valvular heart disease among users of fenfluramine and dexfenfluramine who underwent echocardiography before use of medication.,"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.","[{'text': 'valvular heart disease', 'type': 'Disease', 'start': 9, 'end': 31, 'mesh': 'D006349'}, {'text': 'fenfluramine', 'type': 'Chemical', 'start': 47, 'end': 59, 'mesh': 'D005277'}, {'text': 'dexfenfluramine', 'type': 'Chemical', 'start': 64, 'end': 79, 'mesh': 'D020372'}, {'text': 'fenfluramine', 'type': 'Chemical', 'start': 240, 'end': 252, 'mesh': 'D005277'}, {'text': 'dexfenfluramine', 'type': 'Chemical', 'start': 257, 'end': 272, 'mesh': 'D020372'}, {'text': 'valvular disease', 'type': 'Disease', 'start': 277, 'end': 293, 'mesh': 'D006349'}, {'text': 'valvular abnormalities', 'type': 'Disease', 'start': 393, 'end': 415, 'mesh': 'D006349'}, {'text': 'fenfluramine', 'type': 'Chemical', 'start': 431, 'end': 443, 'mesh': 'D005277'}, {'text': 'dexfenfluramine', 'type': 'Chemical', 'start': 447, 'end': 462, 'mesh': 'D020372'}, {'text': 'fenfluramine', 'type': 'Chemical', 'start': 634, 'end': 646, 'mesh': 'D005277'}, {'text': 'dexfenfluramine', 'type': 'Chemical', 'start': 650, 'end': 665, 'mesh': 'D020372'}, {'text': 'valvulopathy', 'type': 'Disease', 'start': 818, 'end': 830, 'mesh': 'D006349'}, {'text': 'aortic regurgitation', 'type': 'Disease', 'start': 1010, 'end': 1030, 'mesh': 'D001022'}, {'text': 'mitral regurgitation', 'type': 'Disease', 'start': 1043, 'end': 1063, 'mesh': 'D008944'}, {'text': 'fenfluramine', 'type': 'Chemical', 'start': 1129, 'end': 1141, 'mesh': 'D005277'}, {'text': 'phentermine', 'type': 'Chemical', 'start': 1142, 'end': 1153, 'mesh': 'D010645'}, {'text': 'valvular heart disease', 'type': 'Disease', 'start': 1164, 'end': 1186, 'mesh': 'D006349'}, {'text': 'bicuspid aortic valve', 'type': 'Disease', 'start': 1205, 'end': 1226, 'mesh': 'C562388'}, {'text': 'aortic regurgitation', 'type': 'Disease', 'start': 1236, 'end': 1256, 'mesh': 'D001022'}, {'text': 'aortic insufficiency', 'type': 'Disease', 'start': 1342, 'end': 1362, 'mesh': 'D001022'}, {'text': 'valvular heart disease', 'type': 'Disease', 'start': 1418, 'end': 1440, 'mesh': 'D006349'}]"
+770,9636837,Carboplatin toxic effects on the peripheral nervous system of the rat.,"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.","[{'text': 'Carboplatin', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D016190'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 104, 'end': 115, 'mesh': 'D016190'}, {'text': 'CBDCA', 'type': 'Chemical', 'start': 130, 'end': 135, 'mesh': 'D016190'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 142, 'end': 151, 'mesh': 'D002945'}, {'text': 'CDDP', 'type': 'Chemical', 'start': 153, 'end': 157, 'mesh': 'D002945'}, {'text': 'neurotoxic', 'type': 'Disease', 'start': 191, 'end': 201, 'mesh': 'D020258'}, {'text': 'CBDCA', 'type': 'Chemical', 'start': 231, 'end': 236, 'mesh': 'D016190'}, {'text': 'neurotoxic', 'type': 'Disease', 'start': 295, 'end': 305, 'mesh': 'D020258'}, {'text': 'peripheral nervous system damage', 'type': 'Disease', 'start': 388, 'end': 420, 'mesh': 'D010523'}, {'text': 'CBDCA', 'type': 'Chemical', 'start': 472, 'end': 477, 'mesh': 'D016190'}, {'text': 'Neurotoxicity', 'type': 'Disease', 'start': 581, 'end': 594, 'mesh': 'D020258'}, {'text': 'CBDCA', 'type': 'Chemical', 'start': 771, 'end': 776, 'mesh': 'D016190'}, {'text': 'peripheral neurotoxicity', 'type': 'Disease', 'start': 815, 'end': 839, 'mesh': 'D010523'}, {'text': 'Pain', 'type': 'Disease', 'start': 841, 'end': 845, 'mesh': 'D010146'}, {'text': 'CDDP', 'type': 'Chemical', 'start': 1097, 'end': 1101, 'mesh': 'D002945'}, {'text': 'platinum', 'type': 'Chemical', 'start': 1210, 'end': 1218, 'mesh': 'D010984'}, {'text': 'CBDCA', 'type': 'Chemical', 'start': 1277, 'end': 1282, 'mesh': 'D016190'}, {'text': 'CBDCA', 'type': 'Chemical', 'start': 1307, 'end': 1312, 'mesh': 'D016190'}, {'text': 'neurotoxic', 'type': 'Disease', 'start': 1316, 'end': 1326, 'mesh': 'D020258'}, {'text': 'CDDP', 'type': 'Chemical', 'start': 1431, 'end': 1435, 'mesh': 'D002945'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 1461, 'end': 1474, 'mesh': 'D020258'}, {'text': 'CBDCA', 'type': 'Chemical', 'start': 1615, 'end': 1620, 'mesh': 'D016190'}]"
+771,9579567,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).,"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.","[{'text': 'endometrial carcinoma', 'type': 'Disease', 'start': 20, 'end': 41, 'mesh': 'D016889'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 62, 'end': 75, 'mesh': 'D001943'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 191, 'end': 200, 'mesh': 'D013629'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 219, 'end': 232, 'mesh': 'D001943'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 287, 'end': 300, 'mesh': 'D001943'}, {'text': 'endometrial cancer', 'type': 'Disease', 'start': 410, 'end': 428, 'mesh': 'D016889'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 433, 'end': 442, 'mesh': 'D013629'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 488, 'end': 501, 'mesh': 'D001943'}, {'text': 'endometrial cancer', 'type': 'Disease', 'start': 536, 'end': 554, 'mesh': 'D016889'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 571, 'end': 584, 'mesh': 'D001943'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 650, 'end': 663, 'mesh': 'D001943'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 755, 'end': 764, 'mesh': 'D013629'}, {'text': 'endometrial cancer', 'type': 'Disease', 'start': 804, 'end': 822, 'mesh': 'D016889'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 1029, 'end': 1038, 'mesh': 'D013629'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 1267, 'end': 1276, 'mesh': 'D013629'}, {'text': 'endometrial cancer', 'type': 'Disease', 'start': 1395, 'end': 1413, 'mesh': 'D016889'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 1431, 'end': 1440, 'mesh': 'D013629'}, {'text': 'advanced disease', 'type': 'Disease', 'start': 1450, 'end': 1466, 'mesh': 'D020178'}, {'text': 'endometrial cancer', 'type': 'Disease', 'start': 1504, 'end': 1522, 'mesh': 'D016889'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 1597, 'end': 1606, 'mesh': 'D013629'}, {'text': 'endometrial cancer', 'type': 'Disease', 'start': 1610, 'end': 1628, 'mesh': 'D016889'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 1679, 'end': 1692, 'mesh': 'D001943'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 1779, 'end': 1792, 'mesh': 'D001943'}, {'text': 'Endometrial cancers', 'type': 'Disease', 'start': 1794, 'end': 1813, 'mesh': 'D016889'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 1846, 'end': 1855, 'mesh': 'D013629'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 1897, 'end': 1906, 'mesh': 'D013629'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 1911, 'end': 1924, 'mesh': 'D001943'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 2051, 'end': 2060, 'mesh': 'D013629'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 2091, 'end': 2104, 'mesh': 'D001943'}]"
+772,9205462,Granulosa cell tumor of the ovary associated with antecedent tamoxifen use.,"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.","[{'text': 'Granulosa cell tumor of the ovary', 'type': 'Disease', 'start': 0, 'end': 33, 'mesh': 'C537296'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 61, 'end': 70, 'mesh': 'D013629'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 163, 'end': 172, 'mesh': 'D013629'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 230, 'end': 239, 'mesh': 'D013629'}, {'text': 'tumors', 'type': 'Disease', 'start': 260, 'end': 266, 'mesh': 'D009369'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 326, 'end': 335, 'mesh': 'D013629'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 349, 'end': 357, 'mesh': 'D004967'}, {'text': 'breast carcinoma', 'type': 'Disease', 'start': 376, 'end': 392, 'mesh': 'D001943'}, {'text': 'aspartate', 'type': 'Chemical', 'start': 398, 'end': 407, 'mesh': 'D001224'}, {'text': 'alanine', 'type': 'Chemical', 'start': 425, 'end': 432, 'mesh': 'D000409'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 489, 'end': 498, 'mesh': 'D013629'}, {'text': 'granulosa cell tumor of the ovary', 'type': 'Disease', 'start': 608, 'end': 641, 'mesh': 'C537296'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 669, 'end': 678, 'mesh': 'D013629'}, {'text': 'liver dysfunction', 'type': 'Disease', 'start': 687, 'end': 704, 'mesh': 'D017093'}, {'text': 'granulosa cell tumors', 'type': 'Disease', 'start': 734, 'end': 755, 'mesh': 'D006106'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 782, 'end': 791, 'mesh': 'D013629'}]"
+773,9098464,"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.","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.","[{'text': 'adenomyosis', 'type': 'Disease', 'start': 18, 'end': 29, 'mesh': 'D062788'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 46, 'end': 64, 'mesh': 'D006966'}, {'text': 'fluoxetine hydrochloride', 'type': 'Chemical', 'start': 76, 'end': 100, 'mesh': 'D005473'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 114, 'end': 123, 'mesh': 'D012701'}, {'text': 'adenomyosis', 'type': 'Disease', 'start': 147, 'end': 158, 'mesh': 'D062788'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 252, 'end': 262, 'mesh': 'D005473'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 311, 'end': 329, 'mesh': 'D006966'}, {'text': 'adenomyosis', 'type': 'Disease', 'start': 362, 'end': 373, 'mesh': 'D062788'}, {'text': 'Fluoxetine', 'type': 'Chemical', 'start': 383, 'end': 393, 'mesh': 'D005473'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 397, 'end': 406, 'mesh': 'D012701'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 482, 'end': 500, 'mesh': 'D006966'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 1055, 'end': 1065, 'mesh': 'D005473'}, {'text': 'adenomyosis', 'type': 'Disease', 'start': 1198, 'end': 1209, 'mesh': 'D062788'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 1255, 'end': 1265, 'mesh': 'D005473'}, {'text': 'steroids', 'type': 'Chemical', 'start': 1395, 'end': 1403, 'mesh': 'D013256'}, {'text': 'adenomyosis', 'type': 'Disease', 'start': 1504, 'end': 1515, 'mesh': 'D062788'}]"
+774,8424298,Effects of deliberate hypotension induced by labetalol with isoflurane on neuropsychological function.,"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.","[{'text': 'hypotension', 'type': 'Disease', 'start': 22, 'end': 33, 'mesh': 'D007022'}, {'text': 'labetalol', 'type': 'Chemical', 'start': 45, 'end': 54, 'mesh': 'D007741'}, {'text': 'isoflurane', 'type': 'Chemical', 'start': 60, 'end': 70, 'mesh': 'D007530'}, {'text': 'hypotension', 'type': 'Disease', 'start': 128, 'end': 139, 'mesh': 'D007022'}, {'text': 'hypotension', 'type': 'Disease', 'start': 308, 'end': 319, 'mesh': 'D007022'}, {'text': 'labetalol', 'type': 'Chemical', 'start': 331, 'end': 340, 'mesh': 'D007741'}, {'text': 'isoflurane', 'type': 'Chemical', 'start': 346, 'end': 356, 'mesh': 'D007530'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 358, 'end': 369, 'mesh': 'D007022'}, {'text': 'hypotension', 'type': 'Disease', 'start': 405, 'end': 416, 'mesh': 'D007022'}, {'text': 'hypotension', 'type': 'Disease', 'start': 515, 'end': 526, 'mesh': 'D007022'}, {'text': 'hypotension', 'type': 'Disease', 'start': 570, 'end': 581, 'mesh': 'D007022'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 589, 'end': 600, 'mesh': 'D007022'}, {'text': 'anxiety', 'type': 'Disease', 'start': 900, 'end': 907, 'mesh': 'D001008'}, {'text': 'depression', 'type': 'Disease', 'start': 930, 'end': 940, 'mesh': 'D003866'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1264, 'end': 1275, 'mesh': 'D007022'}, {'text': 'labetalol', 'type': 'Chemical', 'start': 1287, 'end': 1296, 'mesh': 'D007741'}, {'text': 'isoflurane', 'type': 'Chemical', 'start': 1302, 'end': 1312, 'mesh': 'D007530'}]"
+775,7880714,Auditory disturbance associated with interscalene brachial plexus block.,"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.","[{'text': 'Bupivacaine', 'type': 'Chemical', 'start': 219, 'end': 230, 'mesh': 'D002045'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 242, 'end': 252, 'mesh': 'D004837'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 312, 'end': 323, 'mesh': 'D002045'}, {'text': 'hearing impairment', 'type': 'Disease', 'start': 510, 'end': 528, 'mesh': 'D034381'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 898, 'end': 909, 'mesh': 'D002045'}, {'text': 'auditory dysfunction', 'type': 'Disease', 'start': 1029, 'end': 1049, 'mesh': 'D006311'}]"
+776,7102237,Midazolam compared with thiopentone as an induction agent.,"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.","[{'text': 'Midazolam', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D008874'}, {'text': 'thiopentone', 'type': 'Chemical', 'start': 24, 'end': 35, 'mesh': 'D013874'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 89, 'end': 100, 'mesh': 'D012601'}, {'text': 'morphine', 'type': 'Chemical', 'start': 103, 'end': 111, 'mesh': 'D009020'}, {'text': 'nitrazepam', 'type': 'Chemical', 'start': 119, 'end': 129, 'mesh': 'D009567'}, {'text': 'midazolam', 'type': 'Chemical', 'start': 188, 'end': 197, 'mesh': 'D008874'}, {'text': 'thiopentone', 'type': 'Chemical', 'start': 255, 'end': 266, 'mesh': 'D013874'}, {'text': 'midazolam', 'type': 'Chemical', 'start': 350, 'end': 359, 'mesh': 'D008874'}, {'text': 'apnoea', 'type': 'Disease', 'start': 381, 'end': 387, 'mesh': 'D001049'}, {'text': 'midazolam', 'type': 'Chemical', 'start': 415, 'end': 424, 'mesh': 'D008874'}, {'text': 'midazolam', 'type': 'Chemical', 'start': 487, 'end': 496, 'mesh': 'D008874'}, {'text': 'thiopentone', 'type': 'Chemical', 'start': 501, 'end': 512, 'mesh': 'D013874'}, {'text': 'Midazolam', 'type': 'Chemical', 'start': 552, 'end': 561, 'mesh': 'D008874'}]"
+777,6769133,Cardiotoxic and possible leukemogenic effects of adriamycin in nonhuman primates.,"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.","[{'text': 'Cardiotoxic', 'type': 'Disease', 'start': 0, 'end': 11, 'mesh': 'D066126'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 49, 'end': 59, 'mesh': 'D004317'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 113, 'end': 123, 'mesh': 'D004317'}, {'text': 'congestive heart failure', 'type': 'Disease', 'start': 211, 'end': 235, 'mesh': 'D006333'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 261, 'end': 271, 'mesh': 'D004317'}, {'text': 'myocardial lesions', 'type': 'Disease', 'start': 377, 'end': 395, 'mesh': 'D001768'}, {'text': 'anthracycline', 'type': 'Chemical', 'start': 427, 'end': 440, 'mesh': 'D018943'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 449, 'end': 463, 'mesh': 'D009202'}, {'text': 'acute myeloblastic leukemia', 'type': 'Disease', 'start': 495, 'end': 522, 'mesh': 'D015470'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 552, 'end': 562, 'mesh': 'D004317'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 662, 'end': 672, 'mesh': 'D004317'}, {'text': 'leukemia', 'type': 'Disease', 'start': 735, 'end': 743, 'mesh': 'D007938'}]"
+778,6292680,Doxorubicin cardiomyopathy in children with left-sided Wilms tumor.,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.,"[{'text': 'Doxorubicin', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D004317'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 12, 'end': 26, 'mesh': 'D009202'}, {'text': 'Wilms tumor', 'type': 'Disease', 'start': 55, 'end': 66, 'mesh': 'D009396'}, {'text': 'Wilms tumor', 'type': 'Disease', 'start': 86, 'end': 97, 'mesh': 'D009396'}, {'text': 'anthracycline', 'type': 'Chemical', 'start': 136, 'end': 149, 'mesh': 'D018943'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 150, 'end': 164, 'mesh': 'D009202'}, {'text': 'tumor', 'type': 'Disease', 'start': 190, 'end': 195, 'mesh': 'D009369'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 227, 'end': 238, 'mesh': 'D004317'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 244, 'end': 258, 'mesh': 'D009202'}, {'text': 'Wilms tumor', 'type': 'Disease', 'start': 319, 'end': 330, 'mesh': 'D009396'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 399, 'end': 410, 'mesh': 'D004317'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 469, 'end': 480, 'mesh': 'D004317'}, {'text': 'Wilms tumor', 'type': 'Disease', 'start': 527, 'end': 538, 'mesh': 'D009396'}]"
+779,3969369,Promotional effects of testosterone and dietary fat on prostate carcinogenesis in genetically susceptible rats.,"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.","[{'text': 'testosterone', 'type': 'Chemical', 'start': 23, 'end': 35, 'mesh': 'D013739'}, {'text': 'carcinogenesis', 'type': 'Disease', 'start': 64, 'end': 78, 'mesh': 'D063646'}, {'text': 'prostate adenocarcinomas', 'type': 'Disease', 'start': 199, 'end': 223, 'mesh': 'D011471'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 317, 'end': 329, 'mesh': 'D013739'}, {'text': 'prostate cancer', 'type': 'Disease', 'start': 379, 'end': 394, 'mesh': 'D011471'}, {'text': 'tumors', 'type': 'Disease', 'start': 459, 'end': 465, 'mesh': 'D009369'}, {'text': 'tumors', 'type': 'Disease', 'start': 504, 'end': 510, 'mesh': 'D009369'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 546, 'end': 558, 'mesh': 'D013739'}, {'text': 'prostate cancer', 'type': 'Disease', 'start': 666, 'end': 681, 'mesh': 'D011471'}, {'text': 'prostate cancer', 'type': 'Disease', 'start': 766, 'end': 781, 'mesh': 'D011471'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 850, 'end': 862, 'mesh': 'D013739'}, {'text': 'prostatitis', 'type': 'Disease', 'start': 878, 'end': 889, 'mesh': 'D011472'}, {'text': 'prostate cancer', 'type': 'Disease', 'start': 1003, 'end': 1018, 'mesh': 'D011471'}]"
+780,3108839,Mitomycin C associated hemolytic uremic syndrome.,"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.","[{'text': 'Mitomycin C', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D016685'}, {'text': 'hemolytic uremic syndrome', 'type': 'Disease', 'start': 23, 'end': 48, 'mesh': 'D006463'}, {'text': 'Mitomycin C', 'type': 'Chemical', 'start': 50, 'end': 61, 'mesh': 'D016685'}, {'text': 'Hemolytic Uremic Syndrome', 'type': 'Disease', 'start': 73, 'end': 98, 'mesh': 'D006463'}, {'text': 'HUS', 'type': 'Disease', 'start': 100, 'end': 103, 'mesh': 'D006463'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 218, 'end': 234, 'mesh': 'D000743'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 236, 'end': 252, 'mesh': 'D013921'}, {'text': 'renal failure', 'type': 'Disease', 'start': 269, 'end': 282, 'mesh': 'D051437'}, {'text': 'mitomycin C', 'type': 'Chemical', 'start': 299, 'end': 310, 'mesh': 'D016685'}, {'text': 'renal failure', 'type': 'Disease', 'start': 384, 'end': 397, 'mesh': 'D051437'}, {'text': 'mitomycin C', 'type': 'Chemical', 'start': 445, 'end': 456, 'mesh': 'D016685'}, {'text': 'renal failure', 'type': 'Disease', 'start': 511, 'end': 524, 'mesh': 'D051437'}, {'text': 'pulmonary edema', 'type': 'Disease', 'start': 528, 'end': 543, 'mesh': 'D011654'}, {'text': 'Renal lesions', 'type': 'Disease', 'start': 545, 'end': 558, 'mesh': 'D051437'}, {'text': 'HUS', 'type': 'Disease', 'start': 599, 'end': 602, 'mesh': 'D006463'}, {'text': 'thrombi', 'type': 'Disease', 'start': 633, 'end': 640, 'mesh': 'D013927'}, {'text': 'ischemic', 'type': 'Disease', 'start': 703, 'end': 711, 'mesh': 'D007511'}, {'text': 'mitomycin C', 'type': 'Chemical', 'start': 815, 'end': 826, 'mesh': 'D016685'}, {'text': 'gastric adenocarcinoma', 'type': 'Disease', 'start': 942, 'end': 964, 'mesh': 'D013274'}, {'text': 'renal failure', 'type': 'Disease', 'start': 979, 'end': 992, 'mesh': 'D051437'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 997, 'end': 1013, 'mesh': 'D013921'}, {'text': 'mitomycin C', 'type': 'Chemical', 'start': 1038, 'end': 1049, 'mesh': 'D016685'}, {'text': 'pulmonary edema', 'type': 'Disease', 'start': 1062, 'end': 1077, 'mesh': 'D011654'}]"
+781,2466960,Continuous ambulatory ECG monitoring during fluorouracil therapy: a prospective study.,"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.","[{'text': 'fluorouracil', 'type': 'Chemical', 'start': 44, 'end': 56, 'mesh': 'D005472'}, {'text': 'cardiac toxicity', 'type': 'Disease', 'start': 133, 'end': 149, 'mesh': 'D066126'}, {'text': 'fluorouracil', 'type': 'Chemical', 'start': 166, 'end': 178, 'mesh': 'D005472'}, {'text': '5-FU', 'type': 'Chemical', 'start': 180, 'end': 184, 'mesh': 'D005472'}, {'text': '5-FU', 'type': 'Chemical', 'start': 347, 'end': 351, 'mesh': 'D005472'}, {'text': 'tumors', 'type': 'Disease', 'start': 384, 'end': 390, 'mesh': 'D009369'}, {'text': 'ischemic', 'type': 'Disease', 'start': 427, 'end': 435, 'mesh': 'D007511'}, {'text': '5-FU', 'type': 'Chemical', 'start': 498, 'end': 502, 'mesh': 'D005472'}, {'text': '5-FU', 'type': 'Chemical', 'start': 539, 'end': 543, 'mesh': 'D005472'}, {'text': 'Anginal', 'type': 'Disease', 'start': 554, 'end': 561, 'mesh': 'D000787'}, {'text': 'angina', 'type': 'Disease', 'start': 603, 'end': 609, 'mesh': 'D000787'}, {'text': '5-FU', 'type': 'Chemical', 'start': 618, 'end': 622, 'mesh': 'D005472'}, {'text': '5-FU', 'type': 'Chemical', 'start': 772, 'end': 776, 'mesh': 'D005472'}, {'text': '5-FU', 'type': 'Chemical', 'start': 804, 'end': 808, 'mesh': 'D005472'}, {'text': 'ischemic', 'type': 'Disease', 'start': 855, 'end': 863, 'mesh': 'D007511'}, {'text': '5-FU', 'type': 'Chemical', 'start': 921, 'end': 925, 'mesh': 'D005472'}, {'text': '5-FU', 'type': 'Chemical', 'start': 958, 'end': 962, 'mesh': 'D005472'}, {'text': '5-FU', 'type': 'Chemical', 'start': 1072, 'end': 1076, 'mesh': 'D005472'}, {'text': '5-FU', 'type': 'Chemical', 'start': 1127, 'end': 1131, 'mesh': 'D005472'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 1206, 'end': 1229, 'mesh': 'D003324'}, {'text': 'sudden death', 'type': 'Disease', 'start': 1255, 'end': 1267, 'mesh': 'D003645'}, {'text': '5-FU', 'type': 'Chemical', 'start': 1348, 'end': 1352, 'mesh': 'D005472'}, {'text': 'ischemia', 'type': 'Disease', 'start': 1449, 'end': 1457, 'mesh': 'D007511'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 1492, 'end': 1515, 'mesh': 'D003324'}]"
+782,2320800,Lethal anuria complicating high dose ifosfamide chemotherapy in a breast cancer patient with an impaired renal function.,"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.","[{'text': 'anuria', 'type': 'Disease', 'start': 7, 'end': 13, 'mesh': 'D001002'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 37, 'end': 47, 'mesh': 'D007069'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 66, 'end': 79, 'mesh': 'D001943'}, {'text': 'impaired renal function', 'type': 'Disease', 'start': 96, 'end': 119, 'mesh': 'D007674'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 158, 'end': 171, 'mesh': 'D001943'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 197, 'end': 206, 'mesh': 'D002945'}, {'text': 'renal failure', 'type': 'Disease', 'start': 241, 'end': 254, 'mesh': 'D051437'}, {'text': 'anuria', 'type': 'Disease', 'start': 260, 'end': 266, 'mesh': 'D001002'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 295, 'end': 305, 'mesh': 'D007069'}, {'text': 'Postrenal failure', 'type': 'Disease', 'start': 307, 'end': 324, 'mesh': 'D007674'}, {'text': 'renal failure', 'type': 'Disease', 'start': 400, 'end': 413, 'mesh': 'D051437'}, {'text': 'hypotension', 'type': 'Disease', 'start': 437, 'end': 448, 'mesh': 'D007022'}, {'text': 'anuria', 'type': 'Disease', 'start': 502, 'end': 508, 'mesh': 'D001002'}, {'text': 'Ifosfamide', 'type': 'Chemical', 'start': 592, 'end': 602, 'mesh': 'D007069'}, {'text': 'nephrotoxic', 'type': 'Disease', 'start': 614, 'end': 625, 'mesh': 'D007674'}, {'text': 'tubulopathies', 'type': 'Disease', 'start': 649, 'end': 662, 'mesh': 'D007674'}, {'text': 'anuria', 'type': 'Disease', 'start': 701, 'end': 707, 'mesh': 'D001002'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 726, 'end': 736, 'mesh': 'D007069'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 786, 'end': 795, 'mesh': 'D002945'}, {'text': 'hypotension', 'type': 'Disease', 'start': 857, 'end': 868, 'mesh': 'D007022'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 898, 'end': 908, 'mesh': 'D007069'}, {'text': 'nephrotoxic', 'type': 'Disease', 'start': 937, 'end': 948, 'mesh': 'D007674'}]"
+783,2220369,Central vein thrombosis and topical dipivalyl epinephrine.,"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.","[{'text': 'vein thrombosis', 'type': 'Disease', 'start': 8, 'end': 23, 'mesh': 'D020246'}, {'text': 'dipivalyl epinephrine', 'type': 'Chemical', 'start': 36, 'end': 57, 'mesh': 'C015173'}, {'text': 'vein thrombosis', 'type': 'Disease', 'start': 123, 'end': 138, 'mesh': 'D020246'}, {'text': 'dipivalyl epinephrine', 'type': 'Chemical', 'start': 210, 'end': 231, 'mesh': 'C015173'}, {'text': 'glaucoma', 'type': 'Disease', 'start': 245, 'end': 253, 'mesh': 'D005901'}]"
+784,326460,Amelioration of bendrofluazide-induced hypokalemia by timolol.,"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.","[{'text': 'bendrofluazide', 'type': 'Chemical', 'start': 16, 'end': 30, 'mesh': 'D001539'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 39, 'end': 50, 'mesh': 'D007008'}, {'text': 'timolol', 'type': 'Chemical', 'start': 54, 'end': 61, 'mesh': 'D013999'}, {'text': 'timolol', 'type': 'Chemical', 'start': 98, 'end': 105, 'mesh': 'D013999'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 129, 'end': 140, 'mesh': 'D007008'}, {'text': 'bendrofluazide', 'type': 'Chemical', 'start': 155, 'end': 169, 'mesh': 'D001539'}, {'text': 'Timolol', 'type': 'Chemical', 'start': 261, 'end': 268, 'mesh': 'D013999'}, {'text': 'aldosterone', 'type': 'Chemical', 'start': 301, 'end': 312, 'mesh': 'D000450'}, {'text': 'potassium', 'type': 'Chemical', 'start': 323, 'end': 332, 'mesh': 'D011188'}, {'text': 'bendrofluazide', 'type': 'Chemical', 'start': 353, 'end': 367, 'mesh': 'D001539'}, {'text': 'sodium', 'type': 'Chemical', 'start': 392, 'end': 398, 'mesh': 'D012964'}, {'text': 'potassium', 'type': 'Chemical', 'start': 399, 'end': 408, 'mesh': 'D011188'}, {'text': 'potassium', 'type': 'Chemical', 'start': 452, 'end': 461, 'mesh': 'D011188'}]"
+785,20331935,A cross-sectional evaluation of the effect of risperidone and selective serotonin reuptake inhibitors on bone mineral density in boys.,"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.","[{'text': 'risperidone', 'type': 'Chemical', 'start': 46, 'end': 57, 'mesh': 'D018967'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 72, 'end': 81, 'mesh': 'D012701'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 208, 'end': 219, 'mesh': 'D018967'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 228, 'end': 246, 'mesh': 'D006966'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 420, 'end': 431, 'mesh': 'D018967'}, {'text': 'Hyperprolactinemia', 'type': 'Disease', 'start': 957, 'end': 975, 'mesh': 'D006966'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 1028, 'end': 1039, 'mesh': 'D018967'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 1071, 'end': 1083, 'mesh': 'D013739'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 1153, 'end': 1171, 'mesh': 'D006966'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 1514, 'end': 1523, 'mesh': 'D012701'}, {'text': 'fractures', 'type': 'Disease', 'start': 1782, 'end': 1791, 'mesh': 'D050723'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 1810, 'end': 1821, 'mesh': 'D018967'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 1881, 'end': 1899, 'mesh': 'D006966'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 1946, 'end': 1957, 'mesh': 'D018967'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 1966, 'end': 1984, 'mesh': 'D006966'}]"
+786,19707748,Seizures associated with levofloxacin: case presentation and literature review.,"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.","[{'text': 'Seizures', 'type': 'Disease', 'start': 0, 'end': 8, 'mesh': 'D012640'}, {'text': 'levofloxacin', 'type': 'Chemical', 'start': 25, 'end': 37, 'mesh': 'D064704'}, {'text': 'seizures', 'type': 'Disease', 'start': 134, 'end': 142, 'mesh': 'D012640'}, {'text': 'levofloxacin', 'type': 'Chemical', 'start': 183, 'end': 195, 'mesh': 'D064704'}, {'text': 'levofloxacin', 'type': 'Chemical', 'start': 347, 'end': 359, 'mesh': 'D064704'}, {'text': 'seizures', 'type': 'Disease', 'start': 368, 'end': 376, 'mesh': 'D012640'}, {'text': 'levofloxacin', 'type': 'Chemical', 'start': 520, 'end': 532, 'mesh': 'D064704'}, {'text': 'levofloxacin', 'type': 'Chemical', 'start': 612, 'end': 624, 'mesh': 'D064704'}, {'text': 'seizures', 'type': 'Disease', 'start': 633, 'end': 641, 'mesh': 'D012640'}, {'text': 'levofloxacin', 'type': 'Chemical', 'start': 742, 'end': 754, 'mesh': 'D064704'}, {'text': 'levofloxacin', 'type': 'Chemical', 'start': 891, 'end': 903, 'mesh': 'D064704'}]"
+787,19692487,Mice lacking mPGES-1 are resistant to lithium-induced polyuria.,"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.","[{'text': 'lithium', 'type': 'Chemical', 'start': 38, 'end': 45, 'mesh': 'D008094'}, {'text': 'polyuria', 'type': 'Disease', 'start': 54, 'end': 62, 'mesh': 'D011141'}, {'text': 'lithium', 'type': 'Chemical', 'start': 125, 'end': 132, 'mesh': 'D008094'}, {'text': 'polyuria', 'type': 'Disease', 'start': 141, 'end': 149, 'mesh': 'D011141'}, {'text': 'prostaglandin', 'type': 'Chemical', 'start': 200, 'end': 213, 'mesh': 'D011453'}, {'text': 'PG', 'type': 'Chemical', 'start': 215, 'end': 217, 'mesh': 'D011453'}, {'text': 'lithium', 'type': 'Chemical', 'start': 296, 'end': 303, 'mesh': 'D008094'}, {'text': 'polyuria', 'type': 'Disease', 'start': 312, 'end': 320, 'mesh': 'D011141'}, {'text': 'prostaglandin E', 'type': 'Chemical', 'start': 353, 'end': 368, 'mesh': 'D011458'}, {'text': 'LiCl', 'type': 'Chemical', 'start': 416, 'end': 420, 'mesh': 'D018021'}, {'text': 'polyuria', 'type': 'Disease', 'start': 484, 'end': 492, 'mesh': 'D011141'}, {'text': 'PGE(2)', 'type': 'Chemical', 'start': 603, 'end': 609, 'mesh': 'D015232'}, {'text': 'lithium', 'type': 'Chemical', 'start': 677, 'end': 684, 'mesh': 'D008094'}, {'text': 'polyuria', 'type': 'Disease', 'start': 693, 'end': 701, 'mesh': 'D011141'}, {'text': 'PGE(2)', 'type': 'Chemical', 'start': 790, 'end': 796, 'mesh': 'D015232'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1006, 'end': 1013, 'mesh': 'D008094'}, {'text': 'Na', 'type': 'Chemical', 'start': 1234, 'end': 1236, 'mesh': 'D012964'}, {'text': 'K', 'type': 'Chemical', 'start': 1237, 'end': 1238, 'mesh': 'D011188'}, {'text': 'Cl', 'type': 'Chemical', 'start': 1240, 'end': 1242, 'mesh': 'D002713'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1347, 'end': 1354, 'mesh': 'D008094'}, {'text': 'PGE(2)', 'type': 'Chemical', 'start': 1512, 'end': 1518, 'mesh': 'D015232'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1528, 'end': 1535, 'mesh': 'D008094'}, {'text': 'polyuria', 'type': 'Disease', 'start': 1544, 'end': 1552, 'mesh': 'D011141'}]"
+788,19289093,Identification of a simple and sensitive microplate method for the detection of oversulfated chondroitin sulfate in heparin products.,"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.","[{'text': 'chondroitin sulfate', 'type': 'Chemical', 'start': 93, 'end': 112, 'mesh': 'D002809'}, {'text': 'heparin', 'type': 'Chemical', 'start': 116, 'end': 123, 'mesh': 'D006493'}, {'text': 'Heparin', 'type': 'Chemical', 'start': 134, 'end': 141, 'mesh': 'D006493'}, {'text': 'heparin', 'type': 'Chemical', 'start': 262, 'end': 269, 'mesh': 'D006493'}, {'text': 'chondroitin sulfate', 'type': 'Chemical', 'start': 330, 'end': 349, 'mesh': 'D002809'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 388, 'end': 399, 'mesh': 'D007022'}, {'text': 'heparin', 'type': 'Chemical', 'start': 480, 'end': 487, 'mesh': 'D006493'}, {'text': 'hypotension', 'type': 'Disease', 'start': 588, 'end': 599, 'mesh': 'D007022'}, {'text': 'heparin', 'type': 'Chemical', 'start': 814, 'end': 821, 'mesh': 'D006493'}, {'text': 'heparin', 'type': 'Chemical', 'start': 883, 'end': 890, 'mesh': 'D006493'}, {'text': 'heparin', 'type': 'Chemical', 'start': 1039, 'end': 1046, 'mesh': 'D006493'}]"
+789,18627295,Doxorubicin cardiomyopathy-induced inflammation and apoptosis are attenuated by gene deletion of the kinin B1 receptor.,"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.","[{'text': 'Doxorubicin', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D004317'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 12, 'end': 26, 'mesh': 'D009202'}, {'text': 'inflammation', 'type': 'Disease', 'start': 35, 'end': 47, 'mesh': 'D007249'}, {'text': 'anthracycline', 'type': 'Chemical', 'start': 140, 'end': 153, 'mesh': 'D018943'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 154, 'end': 165, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 167, 'end': 170, 'mesh': 'D004317'}, {'text': 'cardiotoxic', 'type': 'Disease', 'start': 190, 'end': 201, 'mesh': 'D066126'}, {'text': 'DOX', 'type': 'Chemical', 'start': 351, 'end': 354, 'mesh': 'D004317'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 355, 'end': 369, 'mesh': 'D009202'}, {'text': 'inflammation', 'type': 'Disease', 'start': 436, 'end': 448, 'mesh': 'D007249'}, {'text': 'DOX', 'type': 'Chemical', 'start': 482, 'end': 485, 'mesh': 'D004317'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 494, 'end': 508, 'mesh': 'D009202'}, {'text': 'DOX', 'type': 'Chemical', 'start': 510, 'end': 513, 'mesh': 'D004317'}, {'text': 'cardiac dysfunction', 'type': 'Disease', 'start': 534, 'end': 553, 'mesh': 'D006331'}, {'text': 'cardiac apoptosis', 'type': 'Disease', 'start': 725, 'end': 742, 'mesh': 'D006331'}, {'text': 'DOX', 'type': 'Chemical', 'start': 856, 'end': 859, 'mesh': 'D004317'}, {'text': 'cardiac dysfunction', 'type': 'Disease', 'start': 875, 'end': 894, 'mesh': 'D006331'}, {'text': 'DOX', 'type': 'Chemical', 'start': 920, 'end': 923, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1103, 'end': 1106, 'mesh': 'D004317'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 1107, 'end': 1121, 'mesh': 'D009202'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1297, 'end': 1300, 'mesh': 'D004317'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 1301, 'end': 1315, 'mesh': 'D009202'}]"
+790,18405372,Hepatotoxicity associated with sulfasalazine in inflammatory arthritis: A case series from a local surveillance of serious adverse events.,"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.","[{'text': 'Hepatotoxicity', 'type': 'Disease', 'start': 0, 'end': 14, 'mesh': 'D056486'}, {'text': 'sulfasalazine', 'type': 'Chemical', 'start': 31, 'end': 44, 'mesh': 'D012460'}, {'text': 'arthritis', 'type': 'Disease', 'start': 61, 'end': 70, 'mesh': 'D001168'}, {'text': 'liver failure', 'type': 'Disease', 'start': 473, 'end': 486, 'mesh': 'D017093'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 649, 'end': 663, 'mesh': 'D056486'}, {'text': 'sulfasalazine', 'type': 'Chemical', 'start': 667, 'end': 680, 'mesh': 'D012460'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 893, 'end': 907, 'mesh': 'D056486'}, {'text': 'sulfasalazine', 'type': 'Chemical', 'start': 913, 'end': 926, 'mesh': 'D012460'}, {'text': 'hepatic failure', 'type': 'Disease', 'start': 1102, 'end': 1117, 'mesh': 'D017093'}, {'text': 'skin rash', 'type': 'Disease', 'start': 1232, 'end': 1241, 'mesh': 'D005076'}, {'text': 'eosinophilia', 'type': 'Disease', 'start': 1249, 'end': 1261, 'mesh': 'D004802'}, {'text': 'interstitial nephritis', 'type': 'Disease', 'start': 1270, 'end': 1292, 'mesh': 'D009395'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 1464, 'end': 1478, 'mesh': 'D056486'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 1565, 'end': 1579, 'mesh': 'D056486'}, {'text': 'sulfasalazine', 'type': 'Chemical', 'start': 1585, 'end': 1598, 'mesh': 'D012460'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 1662, 'end': 1676, 'mesh': 'D056486'}, {'text': 'sulfasalazine', 'type': 'Chemical', 'start': 1693, 'end': 1706, 'mesh': 'D012460'}]"
+791,18356633,An evaluation of amikacin nephrotoxicity in the hematology/oncology population.,"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.","[{'text': 'amikacin', 'type': 'Chemical', 'start': 17, 'end': 25, 'mesh': 'D000583'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 26, 'end': 40, 'mesh': 'D007674'}, {'text': 'Amikacin', 'type': 'Chemical', 'start': 80, 'end': 88, 'mesh': 'D000583'}, {'text': 'aminoglycoside', 'type': 'Chemical', 'start': 95, 'end': 109, 'mesh': 'D000617'}, {'text': 'febrile neutropenia', 'type': 'Disease', 'start': 180, 'end': 199, 'mesh': 'D009503'}, {'text': 'infections', 'type': 'Disease', 'start': 220, 'end': 230, 'mesh': 'D007239'}, {'text': 'amikacin', 'type': 'Chemical', 'start': 460, 'end': 468, 'mesh': 'D000583'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 480, 'end': 494, 'mesh': 'D007674'}, {'text': 'aminoglycoside', 'type': 'Chemical', 'start': 753, 'end': 767, 'mesh': 'D000617'}, {'text': 'amikacin', 'type': 'Chemical', 'start': 828, 'end': 836, 'mesh': 'D000583'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 856, 'end': 870, 'mesh': 'D007674'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 904, 'end': 914, 'mesh': 'D003404'}, {'text': 'amikacin', 'type': 'Chemical', 'start': 946, 'end': 954, 'mesh': 'D000583'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1035, 'end': 1049, 'mesh': 'D007674'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1301, 'end': 1315, 'mesh': 'D007674'}]"
+792,16574713,Memory function and serotonin transporter promoter gene polymorphism in ecstasy (MDMA) users.,"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.","[{'text': 'serotonin', 'type': 'Chemical', 'start': 20, 'end': 29, 'mesh': 'D012701'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 72, 'end': 79, 'mesh': 'D018817'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 81, 'end': 85, 'mesh': 'D018817'}, {'text': '3,4-methylenedioxymethamphetamine', 'type': 'Chemical', 'start': 103, 'end': 136, 'mesh': 'D018817'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 138, 'end': 142, 'mesh': 'D018817'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 146, 'end': 153, 'mesh': 'D018817'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 186, 'end': 195, 'mesh': 'D012701'}, {'text': '5-HT', 'type': 'Chemical', 'start': 197, 'end': 201, 'mesh': 'D012701'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 295, 'end': 299, 'mesh': 'D018817'}, {'text': '5-HT', 'type': 'Chemical', 'start': 308, 'end': 312, 'mesh': 'D012701'}, {'text': 'neurotoxic lesions', 'type': 'Disease', 'start': 313, 'end': 331, 'mesh': 'D020258'}, {'text': '5-HT', 'type': 'Chemical', 'start': 354, 'end': 358, 'mesh': 'D012701'}, {'text': '5-HT', 'type': 'Chemical', 'start': 408, 'end': 412, 'mesh': 'D012701'}, {'text': '5-HT', 'type': 'Chemical', 'start': 475, 'end': 479, 'mesh': 'D012701'}, {'text': '5-HT', 'type': 'Chemical', 'start': 585, 'end': 589, 'mesh': 'D012701'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 663, 'end': 667, 'mesh': 'D018817'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 776, 'end': 780, 'mesh': 'D018817'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 860, 'end': 864, 'mesh': 'D018817'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 1014, 'end': 1018, 'mesh': 'D018817'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 1058, 'end': 1062, 'mesh': 'D018817'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 1100, 'end': 1104, 'mesh': 'D018817'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 1505, 'end': 1509, 'mesh': 'D018817'}, {'text': 'memory impairment', 'type': 'Disease', 'start': 1607, 'end': 1624, 'mesh': 'D008569'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 1650, 'end': 1654, 'mesh': 'D018817'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 1737, 'end': 1741, 'mesh': 'D018817'}, {'text': 'impaired memory functioning', 'type': 'Disease', 'start': 1813, 'end': 1840, 'mesh': 'D008569'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 1855, 'end': 1859, 'mesh': 'D018817'}, {'text': 'memory impairments', 'type': 'Disease', 'start': 1889, 'end': 1907, 'mesh': 'D008569'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 1963, 'end': 1967, 'mesh': 'D018817'}]"
+793,15638391,Aging process of epithelial cells of the rat prostate lateral lobe in experimental hyperprolactinemia induced by haloperidol.,"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.","[{'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 83, 'end': 101, 'mesh': 'D006966'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 113, 'end': 124, 'mesh': 'D006220'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 179, 'end': 197, 'mesh': 'D006966'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 210, 'end': 221, 'mesh': 'D006220'}, {'text': 'HAL', 'type': 'Chemical', 'start': 223, 'end': 226, 'mesh': 'D006220'}, {'text': 'PRL', 'type': 'Chemical', 'start': 414, 'end': 417, 'mesh': 'D011388'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 423, 'end': 435, 'mesh': 'D013739'}, {'text': 'T', 'type': 'Chemical', 'start': 437, 'end': 438, 'mesh': 'D013739'}, {'text': 'PRL', 'type': 'Chemical', 'start': 681, 'end': 684, 'mesh': 'D011388'}, {'text': 'T', 'type': 'Chemical', 'start': 721, 'end': 722, 'mesh': 'D013739'}, {'text': 'hypertrophy', 'type': 'Disease', 'start': 835, 'end': 846, 'mesh': 'D006984'}, {'text': 'hyperplasia', 'type': 'Disease', 'start': 862, 'end': 873, 'mesh': 'D006965'}]"
+794,15531665,Does supplemental vitamin C increase cardiovascular disease risk in women with diabetes?,"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.","[{'text': 'vitamin C', 'type': 'Chemical', 'start': 18, 'end': 27, 'mesh': 'D001205'}, {'text': 'cardiovascular disease', 'type': 'Disease', 'start': 37, 'end': 59, 'mesh': 'D002318'}, {'text': 'diabetes', 'type': 'Disease', 'start': 79, 'end': 87, 'mesh': 'D003920'}, {'text': 'Vitamin C', 'type': 'Chemical', 'start': 101, 'end': 110, 'mesh': 'D001205'}, {'text': 'vitamin C', 'type': 'Chemical', 'start': 299, 'end': 308, 'mesh': 'D001205'}, {'text': 'diabetic', 'type': 'Disease', 'start': 312, 'end': 320, 'mesh': 'D003920'}, {'text': 'atherosclerosis', 'type': 'Disease', 'start': 343, 'end': 358, 'mesh': 'D050197'}, {'text': 'vitamin C', 'type': 'Chemical', 'start': 421, 'end': 430, 'mesh': 'D001205'}, {'text': 'cardiovascular disease', 'type': 'Disease', 'start': 457, 'end': 479, 'mesh': 'D002318'}, {'text': 'vitamin C', 'type': 'Chemical', 'start': 521, 'end': 530, 'mesh': 'D001205'}, {'text': 'cardiovascular disease', 'type': 'Disease', 'start': 563, 'end': 585, 'mesh': 'D002318'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 597, 'end': 620, 'mesh': 'D003324'}, {'text': 'stroke', 'type': 'Disease', 'start': 636, 'end': 642, 'mesh': 'D020521'}, {'text': 'diabetic', 'type': 'Disease', 'start': 700, 'end': 708, 'mesh': 'D003920'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 820, 'end': 843, 'mesh': 'D003324'}, {'text': 'cardiovascular disease', 'type': 'Disease', 'start': 912, 'end': 934, 'mesh': 'D002318'}, {'text': 'diabetes', 'type': 'Disease', 'start': 957, 'end': 965, 'mesh': 'D003920'}, {'text': 'diabetes', 'type': 'Disease', 'start': 995, 'end': 1003, 'mesh': 'D003920'}, {'text': 'folate', 'type': 'Chemical', 'start': 1020, 'end': 1026, 'mesh': 'D005492'}, {'text': 'vitamin E', 'type': 'Chemical', 'start': 1028, 'end': 1037, 'mesh': 'D014810'}, {'text': 'beta-carotene', 'type': 'Chemical', 'start': 1043, 'end': 1056, 'mesh': 'D019207'}, {'text': 'cardiovascular disease', 'type': 'Disease', 'start': 1095, 'end': 1117, 'mesh': 'D002318'}, {'text': 'vitamin C', 'type': 'Chemical', 'start': 1212, 'end': 1221, 'mesh': 'D001205'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 1283, 'end': 1306, 'mesh': 'D003324'}, {'text': 'stroke', 'type': 'Disease', 'start': 1372, 'end': 1378, 'mesh': 'D020521'}, {'text': 'vitamin C', 'type': 'Chemical', 'start': 1468, 'end': 1477, 'mesh': 'D001205'}, {'text': 'vitamin C', 'type': 'Chemical', 'start': 1522, 'end': 1531, 'mesh': 'D001205'}, {'text': 'Vitamin C', 'type': 'Chemical', 'start': 1588, 'end': 1597, 'mesh': 'D001205'}, {'text': 'cardiovascular disease', 'type': 'Disease', 'start': 1637, 'end': 1659, 'mesh': 'D002318'}, {'text': 'vitamin C', 'type': 'Chemical', 'start': 1720, 'end': 1729, 'mesh': 'D001205'}, {'text': 'cardiovascular disease', 'type': 'Disease', 'start': 1794, 'end': 1816, 'mesh': 'D002318'}, {'text': 'diabetes', 'type': 'Disease', 'start': 1856, 'end': 1864, 'mesh': 'D003920'}]"
+795,12851669,Absolute and attributable risk of venous thromboembolism in women on combined cyproterone acetate and ethinylestradiol.,"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.","[{'text': 'venous thromboembolism', 'type': 'Disease', 'start': 34, 'end': 56, 'mesh': 'D054556'}, {'text': 'cyproterone acetate', 'type': 'Chemical', 'start': 78, 'end': 97, 'mesh': 'D017373'}, {'text': 'ethinylestradiol', 'type': 'Chemical', 'start': 102, 'end': 118, 'mesh': 'D004997'}, {'text': 'venous thromboembolism', 'type': 'Disease', 'start': 169, 'end': 191, 'mesh': 'D054556'}, {'text': 'VTE', 'type': 'Disease', 'start': 193, 'end': 196, 'mesh': 'D054556'}, {'text': 'cyproterone acetate', 'type': 'Chemical', 'start': 213, 'end': 232, 'mesh': 'D017373'}, {'text': 'ethinylestradiol', 'type': 'Chemical', 'start': 238, 'end': 254, 'mesh': 'D004997'}, {'text': 'CPA', 'type': 'Chemical', 'start': 256, 'end': 259, 'mesh': 'D017373'}, {'text': 'EE', 'type': 'Chemical', 'start': 260, 'end': 262, 'mesh': 'D004997'}, {'text': 'combined oral contraceptives', 'type': 'Chemical', 'start': 284, 'end': 312, 'mesh': 'D003277'}, {'text': 'COCs', 'type': 'Chemical', 'start': 314, 'end': 318, 'mesh': 'D003277'}, {'text': 'VTE', 'type': 'Disease', 'start': 489, 'end': 492, 'mesh': 'D054556'}, {'text': 'COC', 'type': 'Chemical', 'start': 494, 'end': 497, 'mesh': 'D003277'}, {'text': 'COCs', 'type': 'Chemical', 'start': 569, 'end': 573, 'mesh': 'D003277'}, {'text': 'CPA', 'type': 'Chemical', 'start': 578, 'end': 581, 'mesh': 'D017373'}, {'text': 'EE', 'type': 'Chemical', 'start': 582, 'end': 584, 'mesh': 'D004997'}, {'text': 'VTE', 'type': 'Disease', 'start': 709, 'end': 712, 'mesh': 'D054556'}, {'text': 'COCs', 'type': 'Chemical', 'start': 722, 'end': 726, 'mesh': 'D003277'}, {'text': 'levonorgestrel', 'type': 'Chemical', 'start': 755, 'end': 769, 'mesh': 'D016912'}, {'text': 'COCs', 'type': 'Chemical', 'start': 781, 'end': 785, 'mesh': 'D003277'}, {'text': 'CPA', 'type': 'Chemical', 'start': 802, 'end': 805, 'mesh': 'D017373'}, {'text': 'EE', 'type': 'Chemical', 'start': 806, 'end': 808, 'mesh': 'D004997'}, {'text': 'VTE', 'type': 'Disease', 'start': 845, 'end': 848, 'mesh': 'D054556'}, {'text': 'COCs', 'type': 'Chemical', 'start': 916, 'end': 920, 'mesh': 'D003277'}, {'text': 'levonorgestrel', 'type': 'Chemical', 'start': 981, 'end': 995, 'mesh': 'D016912'}, {'text': 'COCs', 'type': 'Chemical', 'start': 1007, 'end': 1011, 'mesh': 'D003277'}, {'text': 'CPA', 'type': 'Chemical', 'start': 1080, 'end': 1083, 'mesh': 'D017373'}, {'text': 'EE', 'type': 'Chemical', 'start': 1084, 'end': 1086, 'mesh': 'D004997'}, {'text': 'VTE', 'type': 'Disease', 'start': 1141, 'end': 1144, 'mesh': 'D054556'}, {'text': 'COCs', 'type': 'Chemical', 'start': 1167, 'end': 1171, 'mesh': 'D003277'}, {'text': 'CPA', 'type': 'Chemical', 'start': 1210, 'end': 1213, 'mesh': 'D017373'}, {'text': 'EE', 'type': 'Chemical', 'start': 1214, 'end': 1216, 'mesh': 'D004997'}]"
+796,12842176,Effect of lindane on hepatic and brain cytochrome P450s and influence of P450 modulation in lindane induced neurotoxicity.,"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.","[{'text': 'lindane', 'type': 'Chemical', 'start': 10, 'end': 17, 'mesh': 'D001556'}, {'text': 'lindane', 'type': 'Chemical', 'start': 92, 'end': 99, 'mesh': 'D001556'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 108, 'end': 121, 'mesh': 'D020258'}, {'text': 'lindane', 'type': 'Chemical', 'start': 146, 'end': 153, 'mesh': 'D001556'}, {'text': 'N-nitrosodimethylamine', 'type': 'Chemical', 'start': 367, 'end': 389, 'mesh': 'D004128'}, {'text': 'NDMA', 'type': 'Chemical', 'start': 403, 'end': 407, 'mesh': 'D004128'}, {'text': 'lindane', 'type': 'Chemical', 'start': 578, 'end': 585, 'mesh': 'D001556'}, {'text': 'NDMA', 'type': 'Chemical', 'start': 1170, 'end': 1174, 'mesh': 'D004128'}, {'text': '3-methylcholanthrene', 'type': 'Chemical', 'start': 1338, 'end': 1358, 'mesh': 'D008748'}, {'text': 'MC', 'type': 'Chemical', 'start': 1360, 'end': 1362, 'mesh': 'D008748'}, {'text': 'lindane', 'type': 'Chemical', 'start': 1451, 'end': 1458, 'mesh': 'D001556'}, {'text': 'convulsions', 'type': 'Disease', 'start': 1467, 'end': 1478, 'mesh': 'D012640'}, {'text': 'phenobarbital', 'type': 'Chemical', 'start': 1498, 'end': 1511, 'mesh': 'D010634'}, {'text': 'ethanol', 'type': 'Chemical', 'start': 1548, 'end': 1555, 'mesh': 'D000431'}, {'text': 'lindane', 'type': 'Chemical', 'start': 1642, 'end': 1649, 'mesh': 'D001556'}, {'text': 'convulsions', 'type': 'Disease', 'start': 1658, 'end': 1669, 'mesh': 'D012640'}, {'text': 'lindane', 'type': 'Chemical', 'start': 1719, 'end': 1726, 'mesh': 'D001556'}, {'text': 'cobalt chloride', 'type': 'Chemical', 'start': 1742, 'end': 1757, 'mesh': 'C018021'}, {'text': 'convulsions', 'type': 'Disease', 'start': 1771, 'end': 1782, 'mesh': 'D012640'}, {'text': 'lindane', 'type': 'Chemical', 'start': 1821, 'end': 1828, 'mesh': 'D001556'}, {'text': 'lindane', 'type': 'Chemical', 'start': 1845, 'end': 1852, 'mesh': 'D001556'}, {'text': 'ethanol', 'type': 'Chemical', 'start': 1895, 'end': 1902, 'mesh': 'D000431'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1965, 'end': 1973, 'mesh': 'D064420'}]"
+797,12745515,Seizure associated with sleep deprivation and sustained-release bupropion.,"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.","[{'text': 'Seizure', 'type': 'Disease', 'start': 0, 'end': 7, 'mesh': 'D012640'}, {'text': 'sleep deprivation', 'type': 'Disease', 'start': 24, 'end': 41, 'mesh': 'D012892'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 64, 'end': 73, 'mesh': 'D016642'}, {'text': 'seizure', 'type': 'Disease', 'start': 116, 'end': 123, 'mesh': 'D012640'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 158, 'end': 167, 'mesh': 'D016642'}, {'text': 'sleep deprivation', 'type': 'Disease', 'start': 176, 'end': 193, 'mesh': 'D012892'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 366, 'end': 375, 'mesh': 'D016642'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 415, 'end': 424, 'mesh': 'D016642'}, {'text': 'seizure', 'type': 'Disease', 'start': 481, 'end': 488, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 604, 'end': 612, 'mesh': 'D012640'}, {'text': 'sleep deprivation', 'type': 'Disease', 'start': 630, 'end': 647, 'mesh': 'D012892'}, {'text': 'bupropion', 'type': 'Chemical', 'start': 671, 'end': 680, 'mesh': 'D016642'}, {'text': 'seizures', 'type': 'Disease', 'start': 692, 'end': 700, 'mesh': 'D012640'}]"
+798,12571256,Nephrotoxic effects in high-risk patients undergoing angiography.,"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.","[{'text': 'Nephrotoxic', 'type': 'Disease', 'start': 0, 'end': 11, 'mesh': 'D007674'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 129, 'end': 140, 'mesh': 'D007674'}, {'text': 'nephrotoxic', 'type': 'Disease', 'start': 186, 'end': 197, 'mesh': 'D007674'}, {'text': 'nephrotoxic', 'type': 'Disease', 'start': 362, 'end': 373, 'mesh': 'D007674'}, {'text': 'iodixanol', 'type': 'Chemical', 'start': 436, 'end': 445, 'mesh': 'C044834'}, {'text': 'iohexol', 'type': 'Chemical', 'start': 513, 'end': 520, 'mesh': 'D007472'}, {'text': 'diabetes', 'type': 'Disease', 'start': 559, 'end': 567, 'mesh': 'D003920'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 579, 'end': 589, 'mesh': 'D003404'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 754, 'end': 764, 'mesh': 'D003404'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 861, 'end': 871, 'mesh': 'D003404'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 984, 'end': 994, 'mesh': 'D003404'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1043, 'end': 1053, 'mesh': 'D003404'}, {'text': 'iodixanol', 'type': 'Chemical', 'start': 1122, 'end': 1131, 'mesh': 'C044834'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1180, 'end': 1190, 'mesh': 'D003404'}, {'text': 'iodixanol', 'type': 'Chemical', 'start': 1224, 'end': 1233, 'mesh': 'C044834'}, {'text': 'iohexol', 'type': 'Chemical', 'start': 1273, 'end': 1280, 'mesh': 'D007472'}, {'text': 'iodixanol', 'type': 'Chemical', 'start': 1315, 'end': 1324, 'mesh': 'C044834'}, {'text': 'iohexol', 'type': 'Chemical', 'start': 1349, 'end': 1356, 'mesh': 'D007472'}, {'text': 'iodixanol', 'type': 'Chemical', 'start': 1462, 'end': 1471, 'mesh': 'C044834'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1513, 'end': 1523, 'mesh': 'D003404'}, {'text': 'iohexol', 'type': 'Chemical', 'start': 1617, 'end': 1624, 'mesh': 'D007472'}, {'text': 'iodixanol', 'type': 'Chemical', 'start': 1693, 'end': 1702, 'mesh': 'C044834'}, {'text': 'iodixanol', 'type': 'Chemical', 'start': 1785, 'end': 1794, 'mesh': 'C044834'}, {'text': 'iohexol', 'type': 'Chemical', 'start': 1867, 'end': 1874, 'mesh': 'D007472'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1922, 'end': 1932, 'mesh': 'D003404'}, {'text': 'iodixanol', 'type': 'Chemical', 'start': 2000, 'end': 2009, 'mesh': 'C044834'}, {'text': 'iohexol', 'type': 'Chemical', 'start': 2049, 'end': 2056, 'mesh': 'D007472'}, {'text': 'iodixanol', 'type': 'Chemical', 'start': 2086, 'end': 2095, 'mesh': 'C044834'}, {'text': 'iohexol', 'type': 'Chemical', 'start': 2125, 'end': 2132, 'mesh': 'D007472'}, {'text': 'Nephropathy', 'type': 'Disease', 'start': 2227, 'end': 2238, 'mesh': 'D007674'}, {'text': 'iodixanol', 'type': 'Chemical', 'start': 2323, 'end': 2332, 'mesh': 'C044834'}]"
+799,9514561,Experimental cranial pain elicited by capsaicin: a PET study.,"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.","[{'text': 'pain', 'type': 'Disease', 'start': 21, 'end': 25, 'mesh': 'D010146'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 38, 'end': 47, 'mesh': 'D002211'}, {'text': 'migraine', 'type': 'Disease', 'start': 141, 'end': 149, 'mesh': 'D008881'}, {'text': 'headache', 'type': 'Disease', 'start': 221, 'end': 229, 'mesh': 'D006261'}, {'text': 'headache', 'type': 'Disease', 'start': 252, 'end': 260, 'mesh': 'D006261'}, {'text': 'migraine', 'type': 'Disease', 'start': 344, 'end': 352, 'mesh': 'D008881'}, {'text': 'migraine', 'type': 'Disease', 'start': 397, 'end': 405, 'mesh': 'D008881'}, {'text': 'pain', 'type': 'Disease', 'start': 471, 'end': 475, 'mesh': 'D010146'}, {'text': 'migraine', 'type': 'Disease', 'start': 567, 'end': 575, 'mesh': 'D008881'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 604, 'end': 613, 'mesh': 'D002211'}, {'text': 'painful', 'type': 'Disease', 'start': 687, 'end': 694, 'mesh': 'D010146'}, {'text': 'migraine', 'type': 'Disease', 'start': 980, 'end': 988, 'mesh': 'D008881'}, {'text': 'pain', 'type': 'Disease', 'start': 1043, 'end': 1047, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 1070, 'end': 1074, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 1245, 'end': 1249, 'mesh': 'D010146'}, {'text': 'headache', 'type': 'Disease', 'start': 1293, 'end': 1301, 'mesh': 'D006261'}, {'text': 'cluster headache', 'type': 'Disease', 'start': 1323, 'end': 1339, 'mesh': 'D003027'}]"
+800,9165568,Neuroleptic malignant syndrome with risperidone.,"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.","[{'text': 'Neuroleptic malignant syndrome', 'type': 'Disease', 'start': 0, 'end': 30, 'mesh': 'D009459'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 36, 'end': 47, 'mesh': 'D018967'}, {'text': 'Neuroleptic malignant syndrome', 'type': 'Disease', 'start': 49, 'end': 79, 'mesh': 'D009459'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 109, 'end': 117, 'mesh': 'D004298'}, {'text': 'Risperidone', 'type': 'Chemical', 'start': 177, 'end': 188, 'mesh': 'D018967'}, {'text': 'benzisoxazole', 'type': 'Chemical', 'start': 192, 'end': 205, 'mesh': 'C441200'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 241, 'end': 250, 'mesh': 'D012701'}, {'text': 'extrapyramidal symptoms', 'type': 'Disease', 'start': 372, 'end': 395, 'mesh': 'D001480'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 401, 'end': 412, 'mesh': 'D018967'}, {'text': 'extrapyramidal symptoms', 'type': 'Disease', 'start': 456, 'end': 479, 'mesh': 'D001480'}, {'text': 'neuroleptic malignant syndrome', 'type': 'Disease', 'start': 513, 'end': 543, 'mesh': 'D009459'}, {'text': 'neuroleptic malignant syndrome', 'type': 'Disease', 'start': 597, 'end': 627, 'mesh': 'D009459'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 651, 'end': 662, 'mesh': 'D018967'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 706, 'end': 717, 'mesh': 'D018967'}, {'text': 'dantrolene', 'type': 'Chemical', 'start': 746, 'end': 756, 'mesh': 'D003620'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 761, 'end': 774, 'mesh': 'D001971'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 854, 'end': 865, 'mesh': 'D018967'}, {'text': 'neuroleptic malignant syndrome', 'type': 'Disease', 'start': 898, 'end': 928, 'mesh': 'D009459'}]"
+801,9154656,Hepatic and extrahepatic angiotensinogen gene expression in rats with acute nephrotic syndrome.,"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.","[{'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 76, 'end': 94, 'mesh': 'D009404'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 150, 'end': 161, 'mesh': 'D000809'}, {'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 203, 'end': 221, 'mesh': 'D009404'}, {'text': 'NS', 'type': 'Disease', 'start': 223, 'end': 225, 'mesh': 'D009404'}, {'text': 'nephrotic', 'type': 'Disease', 'start': 462, 'end': 471, 'mesh': 'D009404'}, {'text': 'NS', 'type': 'Disease', 'start': 497, 'end': 499, 'mesh': 'D009404'}, {'text': 'puromycin amino-nucleoside', 'type': 'Chemical', 'start': 537, 'end': 563, 'mesh': 'D011692'}, {'text': 'PAN', 'type': 'Chemical', 'start': 565, 'end': 568, 'mesh': 'D011692'}, {'text': 'PAN', 'type': 'Chemical', 'start': 671, 'end': 674, 'mesh': 'D011692'}, {'text': 'NS', 'type': 'Disease', 'start': 691, 'end': 693, 'mesh': 'D009404'}, {'text': 'PAN', 'type': 'Chemical', 'start': 913, 'end': 916, 'mesh': 'D011692'}, {'text': 'NS', 'type': 'Disease', 'start': 1046, 'end': 1048, 'mesh': 'D009404'}, {'text': 'PAN', 'type': 'Chemical', 'start': 1060, 'end': 1063, 'mesh': 'D011692'}]"
+802,8911359,Cyclophosphamide associated bladder cancer--a highly aggressive disease: analysis of 12 cases.,"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.","[{'text': 'Cyclophosphamide', 'type': 'Chemical', 'start': 0, 'end': 16, 'mesh': 'D003520'}, {'text': 'bladder cancer', 'type': 'Disease', 'start': 28, 'end': 42, 'mesh': 'D001749'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 169, 'end': 185, 'mesh': 'D003520'}, {'text': 'urothelial cancer', 'type': 'Disease', 'start': 197, 'end': 214, 'mesh': 'D014523'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 305, 'end': 321, 'mesh': 'D003520'}, {'text': 'bladder cancer', 'type': 'Disease', 'start': 333, 'end': 347, 'mesh': 'D001749'}, {'text': 'tumors', 'type': 'Disease', 'start': 376, 'end': 382, 'mesh': 'D009369'}, {'text': 'carcinoma', 'type': 'Disease', 'start': 419, 'end': 428, 'mesh': 'D002277'}, {'text': 'cancer', 'type': 'Disease', 'start': 651, 'end': 657, 'mesh': 'D009369'}, {'text': 'Cyclophosphamide', 'type': 'Chemical', 'start': 740, 'end': 756, 'mesh': 'D003520'}, {'text': 'bladder tumor', 'type': 'Disease', 'start': 768, 'end': 781, 'mesh': 'D001749'}, {'text': 'bladder tumors', 'type': 'Disease', 'start': 889, 'end': 903, 'mesh': 'D001749'}]"
+803,8686832,Leg and back pain after spinal anaesthesia involving hyperbaric 5% lignocaine.,"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.","[{'text': 'Leg and back pain', 'type': 'Disease', 'start': 0, 'end': 17, 'mesh': 'D001416'}, {'text': 'lignocaine', 'type': 'Chemical', 'start': 67, 'end': 77, 'mesh': 'D008012'}, {'text': 'lignocaine', 'type': 'Chemical', 'start': 133, 'end': 143, 'mesh': 'D008012'}, {'text': 'glucose', 'type': 'Chemical', 'start': 155, 'end': 162, 'mesh': 'D005947'}, {'text': 'pain in the legs and/or back', 'type': 'Disease', 'start': 248, 'end': 276, 'mesh': 'D001416'}, {'text': 'pain', 'type': 'Disease', 'start': 444, 'end': 448, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 485, 'end': 489, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 533, 'end': 537, 'mesh': 'D010146'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 557, 'end': 564, 'mesh': 'D000431'}, {'text': 'Leg and/or back pain', 'type': 'Disease', 'start': 611, 'end': 631, 'mesh': 'D001416'}, {'text': 'lignocaine', 'type': 'Chemical', 'start': 688, 'end': 698, 'mesh': 'D008012'}]"
+804,8607407,Acute blood pressure elevations with caffeine in men with borderline systemic hypertension.,"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.","[{'text': 'caffeine', 'type': 'Chemical', 'start': 37, 'end': 45, 'mesh': 'D002110'}, {'text': 'hypertension', 'type': 'Disease', 'start': 78, 'end': 90, 'mesh': 'D006973'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 132, 'end': 140, 'mesh': 'D002110'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 157, 'end': 169, 'mesh': 'D006973'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 211, 'end': 219, 'mesh': 'D002110'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 359, 'end': 371, 'mesh': 'D006973'}, {'text': 'hypertension', 'type': 'Disease', 'start': 558, 'end': 570, 'mesh': 'D006973'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 683, 'end': 691, 'mesh': 'D002110'}, {'text': 'Caffeine', 'type': 'Chemical', 'start': 762, 'end': 770, 'mesh': 'D002110'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 1373, 'end': 1385, 'mesh': 'D006973'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1402, 'end': 1410, 'mesh': 'D002110'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 1442, 'end': 1454, 'mesh': 'D006973'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1485, 'end': 1493, 'mesh': 'D002110'}, {'text': 'hypertensives', 'type': 'Disease', 'start': 1641, 'end': 1654, 'mesh': 'D006973'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1690, 'end': 1698, 'mesh': 'D002110'}]"
+805,8111719,Hallucinations and ifosfamide-induced neurotoxicity.,"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.","[{'text': 'Hallucinations', 'type': 'Disease', 'start': 0, 'end': 14, 'mesh': 'D006212'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 19, 'end': 29, 'mesh': 'D007069'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 38, 'end': 51, 'mesh': 'D020258'}, {'text': 'Hallucinations', 'type': 'Disease', 'start': 65, 'end': 79, 'mesh': 'D006212'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 104, 'end': 117, 'mesh': 'D020258'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 166, 'end': 176, 'mesh': 'D007069'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 192, 'end': 202, 'mesh': 'D007069'}, {'text': 'hallucinations', 'type': 'Disease', 'start': 211, 'end': 225, 'mesh': 'D006212'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 329, 'end': 339, 'mesh': 'D007069'}, {'text': 'hallucinations', 'type': 'Disease', 'start': 348, 'end': 362, 'mesh': 'D006212'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 439, 'end': 449, 'mesh': 'D007069'}, {'text': 'Hallucinations', 'type': 'Disease', 'start': 510, 'end': 524, 'mesh': 'D006212'}, {'text': 'hallucinations', 'type': 'Disease', 'start': 669, 'end': 683, 'mesh': 'D006212'}, {'text': 'Hallucinations', 'type': 'Disease', 'start': 720, 'end': 734, 'mesh': 'D006212'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 777, 'end': 790, 'mesh': 'D020258'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 890, 'end': 900, 'mesh': 'D007069'}, {'text': 'hallucinations', 'type': 'Disease', 'start': 909, 'end': 923, 'mesh': 'D006212'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 964, 'end': 977, 'mesh': 'D020258'}, {'text': 'hallucinatory', 'type': 'Disease', 'start': 993, 'end': 1006, 'mesh': 'D006212'}, {'text': 'agitation', 'type': 'Disease', 'start': 1243, 'end': 1252, 'mesh': 'D011595'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1302, 'end': 1313, 'mesh': 'D006220'}]"
+806,7059267,Chlorpropamide-induced optic neuropathy.,"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.","[{'text': 'Chlorpropamide', 'type': 'Chemical', 'start': 0, 'end': 14, 'mesh': 'D002747'}, {'text': 'optic neuropathy', 'type': 'Disease', 'start': 23, 'end': 39, 'mesh': 'D009901'}, {'text': 'adult-onset diabetes', 'type': 'Disease', 'start': 66, 'end': 86, 'mesh': 'D003924'}, {'text': 'chlorpropamide', 'type': 'Chemical', 'start': 100, 'end': 114, 'mesh': 'D002747'}, {'text': 'Diabenese', 'type': 'Chemical', 'start': 116, 'end': 125, 'mesh': 'D002747'}, {'text': 'toxic optic neuropathy', 'type': 'Disease', 'start': 133, 'end': 155, 'mesh': 'D009901'}, {'text': 'chlorpropamide', 'type': 'Chemical', 'start': 194, 'end': 208, 'mesh': 'D002747'}, {'text': 'Visual loss', 'type': 'Disease', 'start': 218, 'end': 229, 'mesh': 'D014786'}, {'text': 'diabetics', 'type': 'Disease', 'start': 240, 'end': 249, 'mesh': 'D003920'}, {'text': 'optic neuropathy', 'type': 'Disease', 'start': 380, 'end': 396, 'mesh': 'D009901'}, {'text': 'visual loss', 'type': 'Disease', 'start': 451, 'end': 462, 'mesh': 'D014786'}, {'text': 'diabetics', 'type': 'Disease', 'start': 466, 'end': 475, 'mesh': 'D003920'}]"
+807,6381653,Levodopa-induced dyskinesia and thalamotomy.,"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.","[{'text': 'Levodopa', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D007980'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 17, 'end': 27, 'mesh': 'D004409'}, {'text': 'Levodopa', 'type': 'Chemical', 'start': 45, 'end': 53, 'mesh': 'D007980'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 62, 'end': 72, 'mesh': 'D004409'}, {'text': 'Parkinsonism', 'type': 'Disease', 'start': 107, 'end': 119, 'mesh': 'D010302'}, {'text': 'dystonic', 'type': 'Disease', 'start': 153, 'end': 161, 'mesh': 'D020821'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 395, 'end': 403, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 412, 'end': 423, 'mesh': 'D004409'}, {'text': 'thalamic lesions', 'type': 'Disease', 'start': 427, 'end': 443, 'mesh': 'D013786'}, {'text': 'Parkinsonism', 'type': 'Disease', 'start': 482, 'end': 494, 'mesh': 'D010302'}]"
+808,3950060,Factors associated with nephrotoxicity and clinical outcome in patients receiving amikacin.,"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)","[{'text': 'nephrotoxicity', 'type': 'Disease', 'start': 24, 'end': 38, 'mesh': 'D007674'}, {'text': 'amikacin', 'type': 'Chemical', 'start': 82, 'end': 90, 'mesh': 'D000583'}, {'text': 'amikacin', 'type': 'Chemical', 'start': 127, 'end': 135, 'mesh': 'D000583'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 178, 'end': 192, 'mesh': 'D007674'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 345, 'end': 355, 'mesh': 'D003404'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 363, 'end': 373, 'mesh': 'D003404'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 976, 'end': 990, 'mesh': 'D007674'}, {'text': 'nephrotoxic', 'type': 'Disease', 'start': 1209, 'end': 1220, 'mesh': 'D007674'}]"
+809,3311455,Cardiac transplantation: improved quality of survival with a modified immunosuppressive protocol.,"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.","[{'text': 'cyclosporine', 'type': 'Chemical', 'start': 273, 'end': 285, 'mesh': 'D016572'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 447, 'end': 459, 'mesh': 'D016572'}, {'text': 'azathioprine', 'type': 'Chemical', 'start': 539, 'end': 551, 'mesh': 'D001379'}, {'text': 'urea nitrogen', 'type': 'Chemical', 'start': 685, 'end': 698, 'mesh': 'D001806'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 709, 'end': 719, 'mesh': 'D003404'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 783, 'end': 797, 'mesh': 'D007674'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 834, 'end': 846, 'mesh': 'D016572'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 939, 'end': 949, 'mesh': 'D003404'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 993, 'end': 1005, 'mesh': 'D016572'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1024, 'end': 1038, 'mesh': 'D007674'}]"
+810,2051906,Reversible cholestasis with bile duct injury following azathioprine therapy. A case report.,"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.","[{'text': 'cholestasis', 'type': 'Disease', 'start': 11, 'end': 22, 'mesh': 'D002779'}, {'text': 'bile duct injury', 'type': 'Disease', 'start': 28, 'end': 44, 'mesh': 'D002779'}, {'text': 'azathioprine', 'type': 'Chemical', 'start': 55, 'end': 67, 'mesh': 'D001379'}, {'text': 'polymyositis', 'type': 'Disease', 'start': 128, 'end': 140, 'mesh': 'D017285'}, {'text': 'liver disease', 'type': 'Disease', 'start': 174, 'end': 187, 'mesh': 'D008107'}, {'text': 'cholestasis', 'type': 'Disease', 'start': 243, 'end': 254, 'mesh': 'D002779'}, {'text': 'azathioprine', 'type': 'Chemical', 'start': 284, 'end': 296, 'mesh': 'D001379'}, {'text': 'cholestasis', 'type': 'Disease', 'start': 326, 'end': 337, 'mesh': 'D002779'}, {'text': 'Azathioprine', 'type': 'Chemical', 'start': 418, 'end': 430, 'mesh': 'D001379'}, {'text': 'azathioprine', 'type': 'Chemical', 'start': 592, 'end': 604, 'mesh': 'D001379'}, {'text': 'cholestasis', 'type': 'Disease', 'start': 613, 'end': 624, 'mesh': 'D002779'}, {'text': 'bile duct injury', 'type': 'Disease', 'start': 666, 'end': 682, 'mesh': 'D002779'}]"
+811,2021202,Renal function and hemodynamics during prolonged isoflurane-induced hypotension in humans.,"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.","[{'text': 'isoflurane', 'type': 'Chemical', 'start': 49, 'end': 59, 'mesh': 'D007530'}, {'text': 'hypotension', 'type': 'Disease', 'start': 68, 'end': 79, 'mesh': 'D007022'}, {'text': 'isoflurane', 'type': 'Chemical', 'start': 105, 'end': 115, 'mesh': 'D007530'}, {'text': 'hypotension', 'type': 'Disease', 'start': 124, 'end': 135, 'mesh': 'D007022'}, {'text': 'para-aminohippurate', 'type': 'Chemical', 'start': 319, 'end': 338, 'mesh': 'D010130'}, {'text': 'PAH', 'type': 'Chemical', 'start': 340, 'end': 343, 'mesh': 'D010130'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 401, 'end': 409, 'mesh': 'D005283'}, {'text': 'nitrous oxide', 'type': 'Chemical', 'start': 411, 'end': 424, 'mesh': 'D009609'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 426, 'end': 432, 'mesh': 'D010100'}, {'text': 'isoflurane', 'type': 'Chemical', 'start': 438, 'end': 448, 'mesh': 'D007530'}, {'text': 'Hypotension', 'type': 'Disease', 'start': 450, 'end': 461, 'mesh': 'D007022'}, {'text': 'isoflurane', 'type': 'Chemical', 'start': 515, 'end': 525, 'mesh': 'D007530'}, {'text': 'hypotension', 'type': 'Disease', 'start': 698, 'end': 709, 'mesh': 'D007022'}, {'text': 'hypotension', 'type': 'Disease', 'start': 888, 'end': 899, 'mesh': 'D007022'}, {'text': 'isoflurane', 'type': 'Chemical', 'start': 1027, 'end': 1037, 'mesh': 'D007530'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1046, 'end': 1057, 'mesh': 'D007022'}]"
+812,1848636,Debrisoquine phenotype and the pharmacokinetics and beta-2 receptor pharmacodynamics of metoprolol and its enantiomers.,"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)","[{'text': 'Debrisoquine', 'type': 'Chemical', 'start': 0, 'end': 12, 'mesh': 'D003647'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 88, 'end': 98, 'mesh': 'D008790'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 171, 'end': 181, 'mesh': 'D008790'}, {'text': 'debrisoquine', 'type': 'Chemical', 'start': 214, 'end': 226, 'mesh': 'D003647'}, {'text': 'sparteine', 'type': 'Chemical', 'start': 227, 'end': 236, 'mesh': 'D013034'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 442, 'end': 452, 'mesh': 'D008790'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 545, 'end': 555, 'mesh': 'D008790'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 603, 'end': 613, 'mesh': 'D008790'}, {'text': 'terbutaline', 'type': 'Chemical', 'start': 617, 'end': 628, 'mesh': 'D013726'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 637, 'end': 648, 'mesh': 'D007008'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 732, 'end': 742, 'mesh': 'D008790'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 838, 'end': 848, 'mesh': 'D008790'}, {'text': 'terbutaline', 'type': 'Chemical', 'start': 944, 'end': 955, 'mesh': 'D013726'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 1059, 'end': 1069, 'mesh': 'D008790'}, {'text': 'terbutaline', 'type': 'Chemical', 'start': 1149, 'end': 1160, 'mesh': 'D013726'}, {'text': 'potassium', 'type': 'Chemical', 'start': 1227, 'end': 1236, 'mesh': 'D011188'}, {'text': 'terbutaline', 'type': 'Chemical', 'start': 1238, 'end': 1249, 'mesh': 'D013726'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 1251, 'end': 1261, 'mesh': 'D008790'}, {'text': 'alpha-hydroxymetoprolol', 'type': 'Chemical', 'start': 1294, 'end': 1317, 'mesh': 'C029504'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 1389, 'end': 1399, 'mesh': 'D008790'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 1409, 'end': 1419, 'mesh': 'D008790'}, {'text': 'terbutaline', 'type': 'Chemical', 'start': 1434, 'end': 1445, 'mesh': 'D013726'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 1512, 'end': 1522, 'mesh': 'D008790'}, {'text': 'alpha-hydroxymetoprolol', 'type': 'Chemical', 'start': 1523, 'end': 1546, 'mesh': 'C029504'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 1652, 'end': 1662, 'mesh': 'D008790'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 1691, 'end': 1701, 'mesh': 'D008790'}]"
+813,1445986,Cefotetan-induced immune hemolytic anemia.,"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.","[{'text': 'Cefotetan', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D015313'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 25, 'end': 41, 'mesh': 'D000743'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 50, 'end': 66, 'mesh': 'D000743'}, {'text': 'penicillins', 'type': 'Chemical', 'start': 153, 'end': 164, 'mesh': 'D010406'}, {'text': 'cephalosporins', 'type': 'Chemical', 'start': 186, 'end': 200, 'mesh': 'D002511'}, {'text': 'anemia', 'type': 'Disease', 'start': 238, 'end': 244, 'mesh': 'D000740'}, {'text': 'cefotetan', 'type': 'Chemical', 'start': 273, 'end': 282, 'mesh': 'D015313'}, {'text': 'Cefotetan', 'type': 'Chemical', 'start': 284, 'end': 293, 'mesh': 'D015313'}, {'text': 'cefotetan', 'type': 'Chemical', 'start': 474, 'end': 483, 'mesh': 'D015313'}, {'text': 'hemolysis', 'type': 'Disease', 'start': 645, 'end': 654, 'mesh': 'D006461'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 689, 'end': 705, 'mesh': 'D000743'}, {'text': 'cephalosporins', 'type': 'Chemical', 'start': 870, 'end': 884, 'mesh': 'D002511'}]"
+814,982002,Acute renal failure subsequent to the administration of rifampicin. A follow-up study of cases reported earlier.,"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.","[{'text': 'Acute renal failure', 'type': 'Disease', 'start': 0, 'end': 19, 'mesh': 'D058186'}, {'text': 'rifampicin', 'type': 'Chemical', 'start': 56, 'end': 66, 'mesh': 'D012293'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 185, 'end': 204, 'mesh': 'D058186'}, {'text': 'renal failure', 'type': 'Disease', 'start': 275, 'end': 288, 'mesh': 'D051437'}, {'text': 'rifampicin', 'type': 'Chemical', 'start': 330, 'end': 340, 'mesh': 'D012293'}, {'text': 'anuria', 'type': 'Disease', 'start': 360, 'end': 366, 'mesh': 'D001002'}, {'text': 'renal lesions', 'type': 'Disease', 'start': 876, 'end': 889, 'mesh': 'D007674'}]"
+815,343678,Type B hepatitis after needle-stick exposure: prevention with hepatitis B immune globulin. Final report of the Veterans Administration Cooperative Study.,"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.","[{'text': 'Type B hepatitis', 'type': 'Disease', 'start': 0, 'end': 16, 'mesh': 'D006509'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 62, 'end': 73, 'mesh': 'D006509'}, {'text': 'Hepatitis B', 'type': 'Disease', 'start': 154, 'end': 165, 'mesh': 'D006509'}, {'text': 'type B hepatitis', 'type': 'Disease', 'start': 321, 'end': 337, 'mesh': 'D006509'}, {'text': 'hepatitis B surface antigen', 'type': 'Chemical', 'start': 369, 'end': 396, 'mesh': 'D006514'}, {'text': 'HBsAG', 'type': 'Chemical', 'start': 398, 'end': 403, 'mesh': 'D006514'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 431, 'end': 440, 'mesh': 'D056486'}, {'text': 'HBeAg', 'type': 'Chemical', 'start': 788, 'end': 793, 'mesh': 'D006513'}, {'text': 'HBeAg', 'type': 'Chemical', 'start': 820, 'end': 825, 'mesh': 'D006513'}, {'text': 'HBsAg', 'type': 'Chemical', 'start': 904, 'end': 909, 'mesh': 'D006514'}, {'text': 'Hepatitis B', 'type': 'Disease', 'start': 927, 'end': 938, 'mesh': 'D006509'}, {'text': 'type B hepatitis', 'type': 'Disease', 'start': 1008, 'end': 1024, 'mesh': 'D006509'}, {'text': 'type B hepatitis', 'type': 'Disease', 'start': 1129, 'end': 1145, 'mesh': 'D006509'}]"
+816,8888541,Serotonin syndrome from venlafaxine-tranylcypromine interaction.,"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.","[{'text': 'Serotonin syndrome', 'type': 'Disease', 'start': 0, 'end': 18, 'mesh': 'D020230'}, {'text': 'venlafaxine', 'type': 'Chemical', 'start': 24, 'end': 35, 'mesh': 'C047426'}, {'text': 'tranylcypromine', 'type': 'Chemical', 'start': 36, 'end': 51, 'mesh': 'D014191'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 90, 'end': 99, 'mesh': 'D012701'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 137, 'end': 146, 'mesh': 'D012701'}, {'text': 'muscle rigidity', 'type': 'Disease', 'start': 182, 'end': 197, 'mesh': 'D009127'}, {'text': 'salivation', 'type': 'Disease', 'start': 199, 'end': 209, 'mesh': 'D012798'}, {'text': 'confusion', 'type': 'Disease', 'start': 211, 'end': 220, 'mesh': 'D003221'}, {'text': 'agitation', 'type': 'Disease', 'start': 222, 'end': 231, 'mesh': 'D011595'}, {'text': 'hyperthermia', 'type': 'Disease', 'start': 236, 'end': 248, 'mesh': 'D005334'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 367, 'end': 376, 'mesh': 'D012701'}, {'text': 'Venlafaxine', 'type': 'Chemical', 'start': 397, 'end': 408, 'mesh': 'C047426'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 469, 'end': 478, 'mesh': 'D012701'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 483, 'end': 497, 'mesh': 'D009638'}, {'text': 'venlafaxine', 'type': 'Chemical', 'start': 511, 'end': 522, 'mesh': 'C047426'}, {'text': 'serotonin syndrome', 'type': 'Disease', 'start': 561, 'end': 579, 'mesh': 'D020230'}, {'text': 'tranylcypromine', 'type': 'Chemical', 'start': 614, 'end': 629, 'mesh': 'D014191'}, {'text': 'depression', 'type': 'Disease', 'start': 634, 'end': 644, 'mesh': 'D003866'}, {'text': 'venlafaxine', 'type': 'Chemical', 'start': 721, 'end': 732, 'mesh': 'C047426'}, {'text': 'tremors', 'type': 'Disease', 'start': 807, 'end': 814, 'mesh': 'D014202'}, {'text': 'rigidity', 'type': 'Disease', 'start': 819, 'end': 827, 'mesh': 'D009127'}, {'text': 'myoclonic jerks', 'type': 'Disease', 'start': 930, 'end': 945, 'mesh': 'D009207'}, {'text': 'rigidity', 'type': 'Disease', 'start': 947, 'end': 955, 'mesh': 'D009127'}, {'text': 'salivation', 'type': 'Disease', 'start': 957, 'end': 967, 'mesh': 'D012798'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 1170, 'end': 1178, 'mesh': 'D003975'}, {'text': 'muscle rigidity', 'type': 'Disease', 'start': 1211, 'end': 1226, 'mesh': 'D009127'}, {'text': 'hypoventilation', 'type': 'Disease', 'start': 1300, 'end': 1315, 'mesh': 'D007040'}, {'text': 'paralyzed', 'type': 'Disease', 'start': 1325, 'end': 1334, 'mesh': 'D010243'}, {'text': 'muscle rigidity', 'type': 'Disease', 'start': 1346, 'end': 1361, 'mesh': 'D009127'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 1415, 'end': 1431, 'mesh': 'D013921'}, {'text': 'rhabdomyolysis', 'type': 'Disease', 'start': 1555, 'end': 1569, 'mesh': 'D012206'}, {'text': 'paralysis', 'type': 'Disease', 'start': 1733, 'end': 1742, 'mesh': 'D010243'}]"
+817,8106150,Effect of nondopaminergic drugs on L-dopa-induced dyskinesias in MPTP-treated monkeys.,"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.","[{'text': 'L-dopa', 'type': 'Chemical', 'start': 35, 'end': 41, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 50, 'end': 61, 'mesh': 'D004409'}, {'text': 'MPTP', 'type': 'Chemical', 'start': 65, 'end': 69, 'mesh': 'D015632'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 124, 'end': 136, 'mesh': 'D020734'}, {'text': 'MPTP', 'type': 'Chemical', 'start': 152, 'end': 156, 'mesh': 'D015632'}, {'text': 'L-DOPA/benserazide', 'type': 'Chemical', 'start': 198, 'end': 216, 'mesh': 'C005177'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 346, 'end': 356, 'mesh': 'D004409'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 426, 'end': 434, 'mesh': 'D004298'}, {'text': 'L-DOPA', 'type': 'Chemical', 'start': 472, 'end': 478, 'mesh': 'D007980'}, {'text': 'dyskinetic', 'type': 'Disease', 'start': 493, 'end': 503, 'mesh': 'D004409'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 558, 'end': 567, 'mesh': 'D003000'}, {'text': 'physostigmine', 'type': 'Chemical', 'start': 569, 'end': 582, 'mesh': 'D010830'}, {'text': 'methysergide', 'type': 'Chemical', 'start': 584, 'end': 596, 'mesh': 'D008784'}, {'text': '5-MDOT', 'type': 'Chemical', 'start': 598, 'end': 604, 'mesh': '-1'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 606, 'end': 617, 'mesh': 'D011433'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 623, 'end': 629, 'mesh': 'D016291'}, {'text': 'dyskinetic', 'type': 'Disease', 'start': 652, 'end': 662, 'mesh': 'D004409'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 704, 'end': 716, 'mesh': 'D020734'}, {'text': 'yohimbine', 'type': 'Chemical', 'start': 742, 'end': 751, 'mesh': 'D015016'}, {'text': 'meperidine', 'type': 'Chemical', 'start': 756, 'end': 766, 'mesh': 'D008614'}, {'text': 'dyskinetic', 'type': 'Disease', 'start': 793, 'end': 803, 'mesh': 'D004409'}, {'text': 'Baclofen', 'type': 'Chemical', 'start': 815, 'end': 823, 'mesh': 'D001418'}, {'text': 'dystonic', 'type': 'Disease', 'start': 869, 'end': 877, 'mesh': 'D020821'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 886, 'end': 896, 'mesh': 'D004409'}, {'text': 'Atropine', 'type': 'Chemical', 'start': 898, 'end': 906, 'mesh': 'D001285'}, {'text': 'dystonic', 'type': 'Disease', 'start': 921, 'end': 929, 'mesh': 'D020821'}, {'text': 'chorea', 'type': 'Disease', 'start': 945, 'end': 951, 'mesh': 'D002819'}]"
+818,21418164,CCNU (lomustine) toxicity in dogs: a retrospective study (2002-07).,"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.","[{'text': 'CCNU', 'type': 'Chemical', 'start': 0, 'end': 4, 'mesh': 'D008130'}, {'text': 'lomustine', 'type': 'Chemical', 'start': 6, 'end': 15, 'mesh': 'D008130'}, {'text': 'toxicity', 'type': 'Disease', 'start': 17, 'end': 25, 'mesh': 'D064420'}, {'text': '1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea', 'type': 'Chemical', 'start': 204, 'end': 248, 'mesh': 'D008130'}, {'text': 'CCNU', 'type': 'Chemical', 'start': 250, 'end': 254, 'mesh': 'D008130'}, {'text': 'CCNU', 'type': 'Chemical', 'start': 320, 'end': 324, 'mesh': 'D008130'}, {'text': 'CCNU', 'type': 'Chemical', 'start': 481, 'end': 485, 'mesh': 'D008130'}, {'text': 'toxicity', 'type': 'Disease', 'start': 544, 'end': 552, 'mesh': 'D064420'}, {'text': 'CCNU', 'type': 'Chemical', 'start': 554, 'end': 558, 'mesh': 'D008130'}, {'text': 'lymphoma', 'type': 'Disease', 'start': 602, 'end': 610, 'mesh': 'D008223'}, {'text': 'mast cell tumour', 'type': 'Disease', 'start': 612, 'end': 628, 'mesh': 'D034801'}, {'text': 'brain tumour', 'type': 'Disease', 'start': 630, 'end': 642, 'mesh': 'D001932'}, {'text': 'histiocytic tumours', 'type': 'Disease', 'start': 644, 'end': 663, 'mesh': 'D015620'}, {'text': 'epitheliotropic lymphoma', 'type': 'Disease', 'start': 668, 'end': 692, 'mesh': 'D008223'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 742, 'end': 753, 'mesh': 'D009503'}, {'text': 'anaemia', 'type': 'Disease', 'start': 773, 'end': 780, 'mesh': 'D000740'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 803, 'end': 819, 'mesh': 'D013921'}, {'text': 'Gastrointestinal toxicosis', 'type': 'Disease', 'start': 821, 'end': 847, 'mesh': 'D005767'}, {'text': 'vomiting', 'type': 'Disease', 'start': 913, 'end': 921, 'mesh': 'D014839'}, {'text': 'toxicity', 'type': 'Disease', 'start': 947, 'end': 955, 'mesh': 'D064420'}, {'text': 'alanine', 'type': 'Chemical', 'start': 969, 'end': 976, 'mesh': 'D000409'}, {'text': 'hepatic failure', 'type': 'Disease', 'start': 1083, 'end': 1098, 'mesh': 'D017093'}, {'text': 'CCNU', 'type': 'Chemical', 'start': 1122, 'end': 1126, 'mesh': 'D008130'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1138, 'end': 1146, 'mesh': 'D064420'}]"
+819,9121607,Neuroactive steroids protect against pilocarpine- and kainic acid-induced limbic seizures and status epilepticus in mice.,"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.","[{'text': 'steroids', 'type': 'Chemical', 'start': 12, 'end': 20, 'mesh': 'D013256'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 37, 'end': 48, 'mesh': 'D010862'}, {'text': 'kainic acid', 'type': 'Chemical', 'start': 54, 'end': 65, 'mesh': 'D007608'}, {'text': 'seizures', 'type': 'Disease', 'start': 81, 'end': 89, 'mesh': 'D012640'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 94, 'end': 112, 'mesh': 'D013226'}, {'text': 'progesterone', 'type': 'Chemical', 'start': 166, 'end': 178, 'mesh': 'D011374'}, {'text': '3 alpha-hydroxy pregnane-20-ones', 'type': 'Chemical', 'start': 180, 'end': 212, 'mesh': 'D011374'}, {'text': 'deoxycorticosterone', 'type': 'Chemical', 'start': 218, 'end': 237, 'mesh': 'D003900'}, {'text': '3 alpha-hydroxy pregnane-21-diol-20-ones', 'type': 'Chemical', 'start': 239, 'end': 279, 'mesh': 'D003900'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 353, 'end': 364, 'mesh': 'D010862'}, {'text': 'kainic acid', 'type': 'Chemical', 'start': 367, 'end': 378, 'mesh': 'D007608'}, {'text': 'N-methyl-D-aspartate', 'type': 'Chemical', 'start': 384, 'end': 404, 'mesh': 'D016202'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 406, 'end': 410, 'mesh': 'D016202'}, {'text': 'seizures', 'type': 'Disease', 'start': 420, 'end': 428, 'mesh': 'D012640'}, {'text': 'Steroids', 'type': 'Chemical', 'start': 438, 'end': 446, 'mesh': 'D013256'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 583, 'end': 594, 'mesh': 'D010862'}, {'text': 'seizures', 'type': 'Disease', 'start': 634, 'end': 642, 'mesh': 'D012640'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 647, 'end': 665, 'mesh': 'D013226'}, {'text': 'steroids', 'type': 'Chemical', 'start': 868, 'end': 876, 'mesh': 'D013256'}, {'text': 'benzodiazepine', 'type': 'Chemical', 'start': 916, 'end': 930, 'mesh': 'D001569'}, {'text': 'clonazepam', 'type': 'Chemical', 'start': 931, 'end': 941, 'mesh': 'D002998'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 964, 'end': 975, 'mesh': 'D010862'}, {'text': 'seizures', 'type': 'Disease', 'start': 976, 'end': 984, 'mesh': 'D012640'}, {'text': 'steroids', 'type': 'Chemical', 'start': 986, 'end': 994, 'mesh': 'D013256'}, {'text': 'seizure', 'type': 'Disease', 'start': 1130, 'end': 1137, 'mesh': 'D012640'}, {'text': 'clonazepam', 'type': 'Chemical', 'start': 1155, 'end': 1165, 'mesh': 'D002998'}, {'text': 'steroids', 'type': 'Chemical', 'start': 1200, 'end': 1208, 'mesh': 'D013256'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1233, 'end': 1241, 'mesh': 'D064420'}, {'text': 'Steroids', 'type': 'Chemical', 'start': 1243, 'end': 1251, 'mesh': 'D013256'}, {'text': 'seizures', 'type': 'Disease', 'start': 1371, 'end': 1379, 'mesh': 'D012640'}, {'text': 'kainic acid', 'type': 'Chemical', 'start': 1391, 'end': 1402, 'mesh': 'D007608'}, {'text': 'seizures', 'type': 'Disease', 'start': 1464, 'end': 1472, 'mesh': 'D012640'}, {'text': 'steroid', 'type': 'Chemical', 'start': 1509, 'end': 1516, 'mesh': 'D013256'}, {'text': 'kainic acid', 'type': 'Chemical', 'start': 1590, 'end': 1601, 'mesh': 'D007608'}, {'text': 'seizures', 'type': 'Disease', 'start': 1617, 'end': 1625, 'mesh': 'D012640'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 1630, 'end': 1648, 'mesh': 'D013226'}, {'text': 'steroids', 'type': 'Chemical', 'start': 1667, 'end': 1675, 'mesh': 'D013256'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 1714, 'end': 1718, 'mesh': 'D016202'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 1795, 'end': 1799, 'mesh': 'D016202'}, {'text': 'seizures', 'type': 'Disease', 'start': 1800, 'end': 1808, 'mesh': 'D012640'}, {'text': 'steroids', 'type': 'Chemical', 'start': 1852, 'end': 1860, 'mesh': 'D013256'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1904, 'end': 1915, 'mesh': 'D010862'}, {'text': 'kainic acid', 'type': 'Chemical', 'start': 1921, 'end': 1932, 'mesh': 'D007608'}, {'text': 'seizures', 'type': 'Disease', 'start': 1941, 'end': 1949, 'mesh': 'D012640'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 1954, 'end': 1972, 'mesh': 'D013226'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 2038, 'end': 2056, 'mesh': 'D013226'}]"
+820,7905523,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.,"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)","[{'text': 'N-butyl-deoxynojirimycin', 'type': 'Chemical', 'start': 39, 'end': 63, 'mesh': 'C059896'}, {'text': 'SC-48334', 'type': 'Chemical', 'start': 65, 'end': 73, 'mesh': 'C059896'}, {'text': 'zidovudine', 'type': 'Chemical', 'start': 79, 'end': 89, 'mesh': 'D015215'}, {'text': 'HIV-1 infection', 'type': 'Disease', 'start': 107, 'end': 122, 'mesh': 'D015658'}, {'text': 'N-butyl-deoxynojirimycin', 'type': 'Chemical', 'start': 269, 'end': 293, 'mesh': 'C059896'}, {'text': 'SC-48334', 'type': 'Chemical', 'start': 295, 'end': 303, 'mesh': 'C059896'}, {'text': 'zidovudine', 'type': 'Chemical', 'start': 344, 'end': 354, 'mesh': 'D015215'}, {'text': 'zidovudine', 'type': 'Chemical', 'start': 362, 'end': 372, 'mesh': 'D015215'}, {'text': 'zidovudine', 'type': 'Chemical', 'start': 458, 'end': 468, 'mesh': 'D015215'}, {'text': 'SC-48334', 'type': 'Chemical', 'start': 486, 'end': 494, 'mesh': 'C059896'}, {'text': 'zidovudine', 'type': 'Chemical', 'start': 519, 'end': 529, 'mesh': 'D015215'}, {'text': 'zidovudine', 'type': 'Chemical', 'start': 552, 'end': 562, 'mesh': 'D015215'}, {'text': 'zidovudine', 'type': 'Chemical', 'start': 628, 'end': 638, 'mesh': 'D015215'}, {'text': 'zidovudine', 'type': 'Chemical', 'start': 717, 'end': 727, 'mesh': 'D015215'}, {'text': 'SC-48334', 'type': 'Chemical', 'start': 792, 'end': 800, 'mesh': 'C059896'}, {'text': 'immunodeficiency', 'type': 'Disease', 'start': 915, 'end': 931, 'mesh': 'D007153'}, {'text': 'zidovudine', 'type': 'Chemical', 'start': 1048, 'end': 1058, 'mesh': 'D015215'}, {'text': 'zidovudine', 'type': 'Chemical', 'start': 1116, 'end': 1126, 'mesh': 'D015215'}, {'text': 'zidovudine', 'type': 'Chemical', 'start': 1188, 'end': 1198, 'mesh': 'D015215'}, {'text': 'zidovudine', 'type': 'Chemical', 'start': 1403, 'end': 1413, 'mesh': 'D015215'}, {'text': 'Diarrhea', 'type': 'Disease', 'start': 1536, 'end': 1544, 'mesh': 'D003967'}, {'text': 'flatulence', 'type': 'Disease', 'start': 1546, 'end': 1556, 'mesh': 'D005414'}, {'text': 'abdominal pain', 'type': 'Disease', 'start': 1558, 'end': 1572, 'mesh': 'D015746'}, {'text': 'weight loss', 'type': 'Disease', 'start': 1578, 'end': 1589, 'mesh': 'D015431'}]"
+821,3431591,"Recent preclinical and clinical studies with the thymidylate synthase inhibitor N10-propargyl-5,8-dideazafolic acid (CB 3717).","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.","[{'text': 'N10-propargyl-5,8-dideazafolic acid', 'type': 'Chemical', 'start': 80, 'end': 115, 'mesh': 'C031662'}, {'text': 'CB 3717', 'type': 'Chemical', 'start': 117, 'end': 124, 'mesh': 'C031662'}, {'text': 'CB 3717', 'type': 'Chemical', 'start': 127, 'end': 134, 'mesh': 'C031662'}, {'text': 'N10-propargyl-5,8-dideazafolic acid', 'type': 'Chemical', 'start': 136, 'end': 171, 'mesh': 'C031662'}, {'text': 'cytotoxicity', 'type': 'Disease', 'start': 237, 'end': 249, 'mesh': 'D064420'}, {'text': 'CB 3717', 'type': 'Chemical', 'start': 382, 'end': 389, 'mesh': 'C031662'}, {'text': 'CB 3717', 'type': 'Chemical', 'start': 467, 'end': 474, 'mesh': 'C031662'}, {'text': 'CB 3717', 'type': 'Chemical', 'start': 539, 'end': 546, 'mesh': 'C031662'}, {'text': 'CB 3717', 'type': 'Chemical', 'start': 774, 'end': 781, 'mesh': 'C031662'}, {'text': 'CB 3717', 'type': 'Chemical', 'start': 864, 'end': 871, 'mesh': 'C031662'}, {'text': 'cytotoxicity', 'type': 'Disease', 'start': 872, 'end': 884, 'mesh': 'D064420'}, {'text': 'CB 3717', 'type': 'Chemical', 'start': 917, 'end': 924, 'mesh': 'C031662'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 952, 'end': 965, 'mesh': 'D001943'}, {'text': 'ovarian cancer', 'type': 'Disease', 'start': 967, 'end': 981, 'mesh': 'D010051'}, {'text': 'hepatoma', 'type': 'Disease', 'start': 983, 'end': 991, 'mesh': 'D006528'}, {'text': 'mesothelioma', 'type': 'Disease', 'start': 997, 'end': 1009, 'mesh': 'D008654'}, {'text': 'Toxicities', 'type': 'Disease', 'start': 1011, 'end': 1021, 'mesh': 'D064420'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 1031, 'end': 1045, 'mesh': 'D056486'}, {'text': 'malaise', 'type': 'Disease', 'start': 1047, 'end': 1054, 'mesh': 'D005221'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1074, 'end': 1088, 'mesh': 'D007674'}, {'text': 'CB 3717', 'type': 'Chemical', 'start': 1214, 'end': 1221, 'mesh': 'C031662'}, {'text': 'CB 3717', 'type': 'Chemical', 'start': 1307, 'end': 1314, 'mesh': 'C031662'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1434, 'end': 1448, 'mesh': 'D007674'}, {'text': 'renal toxicity', 'type': 'Disease', 'start': 1496, 'end': 1510, 'mesh': 'D007674'}, {'text': 'Hepatotoxicity', 'type': 'Disease', 'start': 1527, 'end': 1541, 'mesh': 'D056486'}, {'text': 'malaise', 'type': 'Disease', 'start': 1546, 'end': 1553, 'mesh': 'D005221'}, {'text': 'CB 3717', 'type': 'Chemical', 'start': 1736, 'end': 1743, 'mesh': 'C031662'}]"
+822,33969,Ethopropazine and benztropine in neuroleptic-induced parkinsonism.,"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.","[{'text': 'Ethopropazine', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'C084820'}, {'text': 'benztropine', 'type': 'Chemical', 'start': 18, 'end': 29, 'mesh': 'D001590'}, {'text': 'parkinsonism', 'type': 'Disease', 'start': 53, 'end': 65, 'mesh': 'D010302'}, {'text': 'ethopropazine', 'type': 'Chemical', 'start': 97, 'end': 110, 'mesh': 'C084820'}, {'text': 'benztropine', 'type': 'Chemical', 'start': 127, 'end': 138, 'mesh': 'D001590'}, {'text': 'parkinsonism', 'type': 'Disease', 'start': 159, 'end': 171, 'mesh': 'D010302'}, {'text': 'fluphenazine enanthate', 'type': 'Chemical', 'start': 183, 'end': 205, 'mesh': 'C017610'}, {'text': 'schizophrenic', 'type': 'Disease', 'start': 212, 'end': 225, 'mesh': 'D012559'}, {'text': 'Ethopropazine', 'type': 'Chemical', 'start': 239, 'end': 252, 'mesh': 'C084820'}, {'text': 'benztropine', 'type': 'Chemical', 'start': 257, 'end': 268, 'mesh': 'D001590'}, {'text': 'parkinsonian symptoms', 'type': 'Disease', 'start': 319, 'end': 340, 'mesh': 'D010302'}, {'text': 'procyclidine', 'type': 'Chemical', 'start': 368, 'end': 380, 'mesh': 'D011352'}, {'text': 'benztropine', 'type': 'Chemical', 'start': 429, 'end': 440, 'mesh': 'D001590'}, {'text': 'tardive dyskinesia', 'type': 'Disease', 'start': 488, 'end': 506, 'mesh': 'D004409'}, {'text': 'procyclindine', 'type': 'Chemical', 'start': 542, 'end': 555, 'mesh': 'D011352'}, {'text': 'anxiety', 'type': 'Disease', 'start': 590, 'end': 597, 'mesh': 'D001008'}, {'text': 'depression', 'type': 'Disease', 'start': 602, 'end': 612, 'mesh': 'D003866'}, {'text': 'ethopropazine', 'type': 'Chemical', 'start': 618, 'end': 631, 'mesh': 'C084820'}, {'text': 'benztropine', 'type': 'Chemical', 'start': 669, 'end': 680, 'mesh': 'D001590'}, {'text': 'parkinsonian symptoms', 'type': 'Disease', 'start': 763, 'end': 784, 'mesh': 'D010302'}]"
+823,16844102,Effect of alpha-tocopherol and deferoxamine on methamphetamine-induced neurotoxicity.,"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.","[{'text': 'alpha-tocopherol', 'type': 'Chemical', 'start': 10, 'end': 26, 'mesh': 'D024502'}, {'text': 'deferoxamine', 'type': 'Chemical', 'start': 31, 'end': 43, 'mesh': 'D003676'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 47, 'end': 62, 'mesh': 'D008694'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 71, 'end': 84, 'mesh': 'D020258'}, {'text': 'Methamphetamine', 'type': 'Chemical', 'start': 86, 'end': 101, 'mesh': 'D008694'}, {'text': 'MA', 'type': 'Chemical', 'start': 103, 'end': 105, 'mesh': 'D008694'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 128, 'end': 141, 'mesh': 'D020258'}, {'text': 'alpha-tocopherol', 'type': 'Chemical', 'start': 252, 'end': 268, 'mesh': 'D024502'}, {'text': 'alpha-TC', 'type': 'Chemical', 'start': 270, 'end': 278, 'mesh': 'D024502'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 305, 'end': 311, 'mesh': 'D010100'}, {'text': 'deferoxamine', 'type': 'Chemical', 'start': 325, 'end': 337, 'mesh': 'D003676'}, {'text': 'DFO', 'type': 'Chemical', 'start': 339, 'end': 342, 'mesh': 'D003676'}, {'text': 'iron', 'type': 'Chemical', 'start': 348, 'end': 352, 'mesh': 'D007501'}, {'text': 'MA', 'type': 'Chemical', 'start': 370, 'end': 372, 'mesh': 'D008694'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 381, 'end': 394, 'mesh': 'D020258'}, {'text': 'MA', 'type': 'Chemical', 'start': 424, 'end': 426, 'mesh': 'D008694'}, {'text': 'alpha-TC', 'type': 'Chemical', 'start': 494, 'end': 502, 'mesh': 'D024502'}, {'text': 'MA', 'type': 'Chemical', 'start': 563, 'end': 565, 'mesh': 'D008694'}, {'text': 'DFO', 'type': 'Chemical', 'start': 584, 'end': 587, 'mesh': 'D003676'}, {'text': 'MA', 'type': 'Chemical', 'start': 628, 'end': 630, 'mesh': 'D008694'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 669, 'end': 677, 'mesh': 'D004298'}, {'text': 'DA', 'type': 'Chemical', 'start': 679, 'end': 681, 'mesh': 'D004298'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 684, 'end': 693, 'mesh': 'D012701'}, {'text': 'MA', 'type': 'Chemical', 'start': 746, 'end': 748, 'mesh': 'D008694'}, {'text': 'alpha-TC', 'type': 'Chemical', 'start': 792, 'end': 800, 'mesh': 'D024502'}, {'text': 'DFO', 'type': 'Chemical', 'start': 805, 'end': 808, 'mesh': 'D003676'}, {'text': 'alpha-TC', 'type': 'Chemical', 'start': 823, 'end': 831, 'mesh': 'D024502'}, {'text': 'DFO', 'type': 'Chemical', 'start': 836, 'end': 839, 'mesh': 'D003676'}, {'text': 'MA', 'type': 'Chemical', 'start': 855, 'end': 857, 'mesh': 'D008694'}, {'text': 'hyperthermia', 'type': 'Disease', 'start': 866, 'end': 878, 'mesh': 'D005334'}, {'text': 'glutathione', 'type': 'Chemical', 'start': 992, 'end': 1003, 'mesh': 'D005978'}, {'text': 'MA', 'type': 'Chemical', 'start': 1035, 'end': 1037, 'mesh': 'D008694'}, {'text': 'alpha-TC', 'type': 'Chemical', 'start': 1099, 'end': 1107, 'mesh': 'D024502'}, {'text': 'DFO', 'type': 'Chemical', 'start': 1112, 'end': 1115, 'mesh': 'D003676'}, {'text': 'alpha-TC', 'type': 'Chemical', 'start': 1136, 'end': 1144, 'mesh': 'D024502'}, {'text': 'DFO', 'type': 'Chemical', 'start': 1149, 'end': 1152, 'mesh': 'D003676'}, {'text': 'MA', 'type': 'Chemical', 'start': 1168, 'end': 1170, 'mesh': 'D008694'}, {'text': 'neuronal damage', 'type': 'Disease', 'start': 1179, 'end': 1194, 'mesh': 'D009422'}]"
+824,14633084,Use of dexamethasone with mesna for the prevention of ifosfamide-induced hemorrhagic cystitis.,"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.","[{'text': 'dexamethasone', 'type': 'Chemical', 'start': 7, 'end': 20, 'mesh': 'D003907'}, {'text': 'mesna', 'type': 'Chemical', 'start': 26, 'end': 31, 'mesh': 'D015080'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 54, 'end': 64, 'mesh': 'D007069'}, {'text': 'HC', 'type': 'Disease', 'start': 122, 'end': 124, 'mesh': 'D006470|D003556'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 173, 'end': 183, 'mesh': 'D007069'}, {'text': 'IFS', 'type': 'Chemical', 'start': 185, 'end': 188, 'mesh': 'D007069'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 247, 'end': 260, 'mesh': 'D003907'}, {'text': 'mesna', 'type': 'Chemical', 'start': 281, 'end': 286, 'mesh': 'D015080'}, {'text': 'IFS', 'type': 'Chemical', 'start': 309, 'end': 312, 'mesh': 'D007069'}, {'text': 'HC', 'type': 'Disease', 'start': 321, 'end': 323, 'mesh': 'D006470|D003556'}, {'text': 'mesna', 'type': 'Chemical', 'start': 409, 'end': 414, 'mesh': 'D015080'}, {'text': 'IFS', 'type': 'Chemical', 'start': 480, 'end': 483, 'mesh': 'D007069'}, {'text': 'mesna', 'type': 'Chemical', 'start': 512, 'end': 517, 'mesh': 'D015080'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 537, 'end': 550, 'mesh': 'D003907'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 565, 'end': 578, 'mesh': 'D003907'}, {'text': 'mesna', 'type': 'Chemical', 'start': 584, 'end': 589, 'mesh': 'D015080'}, {'text': 'Cystitis', 'type': 'Disease', 'start': 591, 'end': 599, 'mesh': 'D003556'}, {'text': 'mesna', 'type': 'Chemical', 'start': 788, 'end': 793, 'mesh': 'D015080'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 799, 'end': 812, 'mesh': 'D003907'}, {'text': 'IFS', 'type': 'Chemical', 'start': 867, 'end': 870, 'mesh': 'D007069'}, {'text': 'IFS', 'type': 'Chemical', 'start': 995, 'end': 998, 'mesh': 'D007069'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 1026, 'end': 1039, 'mesh': 'D003907'}, {'text': 'mesna', 'type': 'Chemical', 'start': 1065, 'end': 1070, 'mesh': 'D015080'}, {'text': 'mesna', 'type': 'Chemical', 'start': 1110, 'end': 1115, 'mesh': 'D015080'}, {'text': 'Dexamethasone', 'type': 'Chemical', 'start': 1166, 'end': 1179, 'mesh': 'D003907'}, {'text': 'mesna', 'type': 'Chemical', 'start': 1200, 'end': 1205, 'mesh': 'D015080'}, {'text': 'IFS', 'type': 'Chemical', 'start': 1232, 'end': 1235, 'mesh': 'D007069'}, {'text': 'HC', 'type': 'Disease', 'start': 1244, 'end': 1246, 'mesh': 'D006470|D003556'}, {'text': 'mesna', 'type': 'Chemical', 'start': 1294, 'end': 1299, 'mesh': 'D015080'}, {'text': 'mesna', 'type': 'Chemical', 'start': 1326, 'end': 1331, 'mesh': 'D015080'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 1343, 'end': 1356, 'mesh': 'D003907'}, {'text': 'HC', 'type': 'Disease', 'start': 1373, 'end': 1375, 'mesh': 'D006470|D003556'}]"
+825,11999899,Behavioral effects of MK-801 on reserpine-treated mice.,"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.","[{'text': 'MK-801', 'type': 'Chemical', 'start': 22, 'end': 28, 'mesh': 'D016291'}, {'text': 'reserpine', 'type': 'Chemical', 'start': 32, 'end': 41, 'mesh': 'D012110'}, {'text': 'dizocilpine', 'type': 'Chemical', 'start': 71, 'end': 82, 'mesh': 'D016291'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 84, 'end': 90, 'mesh': 'D016291'}, {'text': 'N-methyl-D-aspartate', 'type': 'Chemical', 'start': 110, 'end': 130, 'mesh': 'D016202'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 132, 'end': 136, 'mesh': 'D016202'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 175, 'end': 183, 'mesh': 'D004298'}, {'text': 'reserpine', 'type': 'Chemical', 'start': 213, 'end': 222, 'mesh': 'D012110'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 306, 'end': 325, 'mesh': 'D010300'}, {'text': 'tardive dyskinesia', 'type': 'Disease', 'start': 330, 'end': 348, 'mesh': 'D004409'}, {'text': 'Reserpine', 'type': 'Chemical', 'start': 397, 'end': 406, 'mesh': 'D012110'}, {'text': 'orofacial dyskinesia', 'type': 'Disease', 'start': 486, 'end': 506, 'mesh': 'D009069'}, {'text': 'tardive dyskinesia', 'type': 'Disease', 'start': 585, 'end': 603, 'mesh': 'D004409'}, {'text': 'Reserpine', 'type': 'Chemical', 'start': 605, 'end': 614, 'mesh': 'D012110'}, {'text': 'tremor', 'type': 'Disease', 'start': 629, 'end': 635, 'mesh': 'D014202'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 640, 'end': 649, 'mesh': 'D002375'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 681, 'end': 700, 'mesh': 'D010300'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 702, 'end': 708, 'mesh': 'D016291'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 835, 'end': 844, 'mesh': 'D002375'}, {'text': 'reserpine', 'type': 'Chemical', 'start': 856, 'end': 865, 'mesh': 'D012110'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 876, 'end': 882, 'mesh': 'D016291'}, {'text': 'tremor', 'type': 'Disease', 'start': 928, 'end': 934, 'mesh': 'D014202'}, {'text': 'reserpine', 'type': 'Chemical', 'start': 938, 'end': 947, 'mesh': 'D012110'}, {'text': 'Reserpine', 'type': 'Chemical', 'start': 962, 'end': 971, 'mesh': 'D012110'}, {'text': 'apomophine', 'type': 'Chemical', 'start': 1035, 'end': 1045, 'mesh': 'D001058'}, {'text': 'oral dyskinesia', 'type': 'Disease', 'start': 1107, 'end': 1122, 'mesh': 'D009069'}, {'text': 'reserpine', 'type': 'Chemical', 'start': 1151, 'end': 1160, 'mesh': 'D012110'}, {'text': 'tremor', 'type': 'Disease', 'start': 1182, 'end': 1188, 'mesh': 'D014202'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 1193, 'end': 1202, 'mesh': 'D002375'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 1229, 'end': 1235, 'mesh': 'D016291'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 1278, 'end': 1287, 'mesh': 'D002375'}, {'text': 'tremor', 'type': 'Disease', 'start': 1292, 'end': 1298, 'mesh': 'D014202'}, {'text': 'reserpine', 'type': 'Chemical', 'start': 1310, 'end': 1319, 'mesh': 'D012110'}, {'text': 'reserpine', 'type': 'Chemical', 'start': 1339, 'end': 1348, 'mesh': 'D012110'}, {'text': 'tremor', 'type': 'Disease', 'start': 1487, 'end': 1493, 'mesh': 'D014202'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 1498, 'end': 1507, 'mesh': 'D002375'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 1517, 'end': 1523, 'mesh': 'D016291'}, {'text': 'reserpine', 'type': 'Chemical', 'start': 1593, 'end': 1602, 'mesh': 'D012110'}, {'text': 'reserpine', 'type': 'Chemical', 'start': 1628, 'end': 1637, 'mesh': 'D012110'}, {'text': 'abnormal movements', 'type': 'Disease', 'start': 1661, 'end': 1679, 'mesh': 'D004409'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 1754, 'end': 1766, 'mesh': 'D010300'}, {'text': 'tardive dsykinesia', 'type': 'Disease', 'start': 1776, 'end': 1794, 'mesh': 'D004409'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 1841, 'end': 1845, 'mesh': 'D016202'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 1926, 'end': 1935, 'mesh': 'D002375'}, {'text': 'tremor', 'type': 'Disease', 'start': 1940, 'end': 1946, 'mesh': 'D014202'}]"
+826,9431903,Effect of glyceryl trinitrate on the sphincter of Oddi spasm evoked by prostigmine-morphine administration.,"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.","[{'text': 'glyceryl trinitrate', 'type': 'Chemical', 'start': 10, 'end': 29, 'mesh': 'D005996'}, {'text': 'prostigmine', 'type': 'Chemical', 'start': 71, 'end': 82, 'mesh': 'D009388'}, {'text': 'morphine', 'type': 'Chemical', 'start': 83, 'end': 91, 'mesh': 'D009020'}, {'text': 'glyceryl trinitrate', 'type': 'Chemical', 'start': 147, 'end': 166, 'mesh': 'D005996'}, {'text': 'prostigmine', 'type': 'Chemical', 'start': 174, 'end': 185, 'mesh': 'D009388'}, {'text': 'morphine', 'type': 'Chemical', 'start': 186, 'end': 194, 'mesh': 'D009020'}, {'text': 'sphincter of Oddi dyskinesia', 'type': 'Disease', 'start': 270, 'end': 298, 'mesh': 'D046628'}, {'text': 'prostigmine', 'type': 'Chemical', 'start': 347, 'end': 358, 'mesh': 'D009388'}, {'text': 'morphine', 'type': 'Chemical', 'start': 359, 'end': 367, 'mesh': 'D009020'}, {'text': 'prostigmine', 'type': 'Chemical', 'start': 391, 'end': 402, 'mesh': 'D009388'}, {'text': 'morphine', 'type': 'Chemical', 'start': 429, 'end': 437, 'mesh': 'D009020'}, {'text': 'glyceryl trinitrate', 'type': 'Chemical', 'start': 554, 'end': 573, 'mesh': 'D005996'}, {'text': 'Nitrolingual', 'type': 'Chemical', 'start': 584, 'end': 596, 'mesh': 'D005996'}, {'text': 'Prostigmine', 'type': 'Chemical', 'start': 636, 'end': 647, 'mesh': 'D009388'}, {'text': 'morphine', 'type': 'Chemical', 'start': 648, 'end': 656, 'mesh': 'D009020'}, {'text': 'spasm', 'type': 'Disease', 'start': 1080, 'end': 1085, 'mesh': 'D013035'}, {'text': 'Glyceryl trinitrate', 'type': 'Chemical', 'start': 1125, 'end': 1144, 'mesh': 'D005996'}, {'text': 'prostigmine', 'type': 'Chemical', 'start': 1180, 'end': 1191, 'mesh': 'D009388'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1192, 'end': 1200, 'mesh': 'D009020'}, {'text': 'glyceryl trinitrate', 'type': 'Chemical', 'start': 1507, 'end': 1526, 'mesh': 'D005996'}, {'text': 'glyceryl trinitrate', 'type': 'Chemical', 'start': 1605, 'end': 1624, 'mesh': 'D005996'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1632, 'end': 1640, 'mesh': 'D009020'}, {'text': 'glyceryl trinitrate', 'type': 'Chemical', 'start': 1690, 'end': 1709, 'mesh': 'D005996'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1757, 'end': 1765, 'mesh': 'D009020'}, {'text': 'sphincter of Oddi dyskinesia', 'type': 'Disease', 'start': 1812, 'end': 1840, 'mesh': 'D046628'}]"
+827,8665051,Effects of acute steroid administration on ventilatory and peripheral muscles in rats.,"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 alone.","[{'text': 'steroid', 'type': 'Chemical', 'start': 17, 'end': 24, 'mesh': 'D013256'}, {'text': 'myopathy', 'type': 'Disease', 'start': 133, 'end': 141, 'mesh': 'D009135'}, {'text': 'corticosteroids', 'type': 'Chemical', 'start': 194, 'end': 209, 'mesh': 'D000305'}, {'text': 'myopathy', 'type': 'Disease', 'start': 233, 'end': 241, 'mesh': 'D009135'}, {'text': 'methylprednisolone', 'type': 'Chemical', 'start': 353, 'end': 371, 'mesh': 'D008775'}, {'text': 'M', 'type': 'Chemical', 'start': 373, 'end': 374, 'mesh': 'D008775'}, {'text': 'triamcinolone', 'type': 'Chemical', 'start': 380, 'end': 393, 'mesh': 'D014221'}, {'text': 'T', 'type': 'Chemical', 'start': 395, 'end': 396, 'mesh': 'D014221'}, {'text': 'reduction of food intake', 'type': 'Disease', 'start': 489, 'end': 513, 'mesh': 'D000855'}, {'text': 'steroid', 'type': 'Chemical', 'start': 521, 'end': 528, 'mesh': 'D013256'}, {'text': 'M', 'type': 'Chemical', 'start': 561, 'end': 562, 'mesh': 'D008775'}, {'text': 'T', 'type': 'Chemical', 'start': 567, 'end': 568, 'mesh': 'D014221'}, {'text': 'loss in body weight', 'type': 'Disease', 'start': 620, 'end': 639, 'mesh': 'D015431'}, {'text': 'steroid', 'type': 'Chemical', 'start': 833, 'end': 840, 'mesh': 'D013256'}, {'text': 'M', 'type': 'Chemical', 'start': 946, 'end': 947, 'mesh': 'D008775'}, {'text': 'T', 'type': 'Chemical', 'start': 994, 'end': 995, 'mesh': 'D014221'}, {'text': 'steroid', 'type': 'Chemical', 'start': 1072, 'end': 1079, 'mesh': 'D013256'}, {'text': 'M', 'type': 'Chemical', 'start': 1129, 'end': 1130, 'mesh': 'D008775'}, {'text': 'tetanic', 'type': 'Disease', 'start': 1140, 'end': 1147, 'mesh': 'D013746'}, {'text': 'Steroid', 'type': 'Chemical', 'start': 1171, 'end': 1178, 'mesh': 'D013256'}, {'text': 'atrophy', 'type': 'Disease', 'start': 1403, 'end': 1410, 'mesh': 'D009133'}, {'text': 'steroid', 'type': 'Chemical', 'start': 1418, 'end': 1425, 'mesh': 'D013256'}, {'text': 'atrophy', 'type': 'Disease', 'start': 1465, 'end': 1472, 'mesh': 'D009133'}, {'text': 'T', 'type': 'Chemical', 'start': 1478, 'end': 1479, 'mesh': 'D014221'}, {'text': 'necrosis', 'type': 'Disease', 'start': 1564, 'end': 1572, 'mesh': 'D009336'}, {'text': 'T', 'type': 'Chemical', 'start': 1631, 'end': 1632, 'mesh': 'D014221'}, {'text': 'muscle atrophy', 'type': 'Disease', 'start': 1655, 'end': 1669, 'mesh': 'D009133'}, {'text': 'T', 'type': 'Chemical', 'start': 1725, 'end': 1726, 'mesh': 'D014221'}, {'text': 'steroids', 'type': 'Chemical', 'start': 1808, 'end': 1816, 'mesh': 'D013256'}, {'text': 'steroids', 'type': 'Chemical', 'start': 1887, 'end': 1895, 'mesh': 'D013256'}, {'text': 'atrophy', 'type': 'Disease', 'start': 1927, 'end': 1934, 'mesh': 'D001284'}, {'text': 'steroid', 'type': 'Chemical', 'start': 2023, 'end': 2030, 'mesh': 'D013256'}, {'text': 'necrosis', 'type': 'Disease', 'start': 2045, 'end': 2053, 'mesh': 'D009336'}, {'text': 'atrophy', 'type': 'Disease', 'start': 2068, 'end': 2075, 'mesh': 'D009133'}]"
+828,7785794,Refractory cardiogenic shock and complete heart block after verapamil SR and metoprolol treatment. A case report.,"A seventy-eight-year-old woman presented with complete heart block and refractory hypotension two days after a therapeutic dose of sustained-release verapamil with concomitant use of metoprolol. The patient continued to remain hypotensive with complete heart block, even with multiple uses of intravenous atropine as well as high doses of pressor agents such as dopamine and dobutamine. However, shortly after the use of intravenous calcium chloride, the refractory hypotension and complete heart block resolved.","[{'text': 'cardiogenic shock', 'type': 'Disease', 'start': 11, 'end': 28, 'mesh': 'D012770'}, {'text': 'heart block', 'type': 'Disease', 'start': 42, 'end': 53, 'mesh': 'D006327'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 60, 'end': 69, 'mesh': 'D014700'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 77, 'end': 87, 'mesh': 'D008790'}, {'text': 'heart block', 'type': 'Disease', 'start': 169, 'end': 180, 'mesh': 'D006327'}, {'text': 'hypotension', 'type': 'Disease', 'start': 196, 'end': 207, 'mesh': 'D007022'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 263, 'end': 272, 'mesh': 'D014700'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 297, 'end': 307, 'mesh': 'D008790'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 341, 'end': 352, 'mesh': 'D007022'}, {'text': 'heart block', 'type': 'Disease', 'start': 367, 'end': 378, 'mesh': 'D006327'}, {'text': 'atropine', 'type': 'Chemical', 'start': 419, 'end': 427, 'mesh': 'D001285'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 476, 'end': 484, 'mesh': 'D004298'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 489, 'end': 499, 'mesh': 'D004280'}, {'text': 'calcium chloride', 'type': 'Chemical', 'start': 547, 'end': 563, 'mesh': 'D002122'}, {'text': 'hypotension', 'type': 'Disease', 'start': 580, 'end': 591, 'mesh': 'D007022'}, {'text': 'heart block', 'type': 'Disease', 'start': 605, 'end': 616, 'mesh': 'D006327'}]"
+829,8958188,A phase I clinical study of the antipurine antifolate lometrexol (DDATHF) given with oral folic acid.,"Lometrexol is an antifolate which inhibits glycinamide ribonucleotide formyltransferase (GARFT), an enzyme essential for de novo purine synthesis. Extensive experimental and limited clinical data have shown that lometrexol has activity against tumours which are refractory to other drugs, notably methotrexate. However, the initial clinical development of lometrexol was curtailed because of severe and cumulative antiproliferative toxicities. Preclinical murine studies demonstrated that the toxicity of lometrexol can be prevented by low dose folic acid administration, i.e. for 7 days prior to and 7 days following a single bolus dose. 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. This information will facilitate the future evaluation of this class of compounds in cancer therapy.","[{'text': 'antipurine', 'type': 'Chemical', 'start': 32, 'end': 42, 'mesh': 'D000983'}, {'text': 'lometrexol', 'type': 'Chemical', 'start': 54, 'end': 64, 'mesh': 'C045894'}, {'text': 'DDATHF', 'type': 'Chemical', 'start': 66, 'end': 72, 'mesh': 'C045894'}, {'text': 'folic acid', 'type': 'Chemical', 'start': 90, 'end': 100, 'mesh': 'D005492'}, {'text': 'Lometrexol', 'type': 'Chemical', 'start': 102, 'end': 112, 'mesh': 'C045894'}, {'text': 'glycinamide ribonucleotide', 'type': 'Chemical', 'start': 145, 'end': 171, 'mesh': 'C402896'}, {'text': 'purine', 'type': 'Chemical', 'start': 231, 'end': 237, 'mesh': 'D011687'}, {'text': 'lometrexol', 'type': 'Chemical', 'start': 314, 'end': 324, 'mesh': 'C045894'}, {'text': 'tumours', 'type': 'Disease', 'start': 346, 'end': 353, 'mesh': 'D009369'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 399, 'end': 411, 'mesh': 'D008727'}, {'text': 'lometrexol', 'type': 'Chemical', 'start': 458, 'end': 468, 'mesh': 'C045894'}, {'text': 'toxicities', 'type': 'Disease', 'start': 534, 'end': 544, 'mesh': 'D064420'}, {'text': 'toxicity', 'type': 'Disease', 'start': 595, 'end': 603, 'mesh': 'D064420'}, {'text': 'lometrexol', 'type': 'Chemical', 'start': 607, 'end': 617, 'mesh': 'C045894'}, {'text': 'folic acid', 'type': 'Chemical', 'start': 647, 'end': 657, 'mesh': 'D005492'}, {'text': 'lometrexol', 'type': 'Chemical', 'start': 795, 'end': 805, 'mesh': 'C045894'}, {'text': 'folic acid', 'type': 'Chemical', 'start': 817, 'end': 827, 'mesh': 'D005492'}, {'text': 'toxicity', 'type': 'Disease', 'start': 873, 'end': 881, 'mesh': 'D064420'}, {'text': 'lometrexol', 'type': 'Chemical', 'start': 885, 'end': 895, 'mesh': 'C045894'}, {'text': 'folic acid', 'type': 'Chemical', 'start': 923, 'end': 933, 'mesh': 'D005492'}, {'text': 'Thrombocytopenia', 'type': 'Disease', 'start': 951, 'end': 967, 'mesh': 'D013921'}, {'text': 'mucositis', 'type': 'Disease', 'start': 972, 'end': 981, 'mesh': 'D052016'}, {'text': 'toxicities', 'type': 'Disease', 'start': 997, 'end': 1007, 'mesh': 'D064420'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1058, 'end': 1066, 'mesh': 'D064420'}, {'text': 'folate', 'type': 'Chemical', 'start': 1092, 'end': 1098, 'mesh': 'D005492'}, {'text': 'lometrexol', 'type': 'Chemical', 'start': 1147, 'end': 1157, 'mesh': 'C045894'}, {'text': 'folic acid', 'type': 'Chemical', 'start': 1202, 'end': 1212, 'mesh': 'D005492'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1282, 'end': 1290, 'mesh': 'D064420'}, {'text': 'lometrexol', 'type': 'Chemical', 'start': 1304, 'end': 1314, 'mesh': 'C045894'}, {'text': 'cancer', 'type': 'Disease', 'start': 1564, 'end': 1570, 'mesh': 'D009369'}]"
+830,2557556,Involvement of the mu-opiate receptor in peripheral analgesia.,"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.","[{'text': 'analgesia', 'type': 'Disease', 'start': 52, 'end': 61, 'mesh': 'D000699'}, {'text': 'morphine', 'type': 'Chemical', 'start': 96, 'end': 104, 'mesh': 'D009020'}, {'text': 'Tyr-D-Ala-Gly-NMe-Phe-Gly-ol', 'type': 'Chemical', 'start': 106, 'end': 134, 'mesh': 'D020875'}, {'text': 'morphiceptin', 'type': 'Chemical', 'start': 139, 'end': 151, 'mesh': 'C028889'}, {'text': 'trans-3,4-dichloro-N-methyl-N[2-(1-pyrrolidinyl) cyclohexyl]benzeneactemide', 'type': 'Chemical', 'start': 161, 'end': 236, 'mesh': 'D019900'}, {'text': '[D-Pen2.5]-enkephalin', 'type': 'Chemical', 'start': 249, 'end': 270, 'mesh': 'D020881'}, {'text': '[D-Ser2]-[Leu]enkephalin-Thr', 'type': 'Chemical', 'start': 275, 'end': 303, 'mesh': 'C034318'}, {'text': 'prostaglandin E2', 'type': 'Chemical', 'start': 556, 'end': 572, 'mesh': 'D015232'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 581, 'end': 593, 'mesh': 'D006930'}, {'text': 'morphine', 'type': 'Chemical', 'start': 634, 'end': 642, 'mesh': 'D009020'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 679, 'end': 687, 'mesh': 'D009270'}, {'text': 'Morphine', 'type': 'Chemical', 'start': 738, 'end': 746, 'mesh': 'D009020'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 775, 'end': 787, 'mesh': 'D006930'}, {'text': '8-bromo cyclic adenosine monophosphate', 'type': 'Chemical', 'start': 799, 'end': 837, 'mesh': 'D015124'}, {'text': 'cyclic adenosine monophosphate', 'type': 'Chemical', 'start': 1060, 'end': 1090, 'mesh': 'D000242'}]"
+831,15580403,Adequate timing of ribavirin reduction in patients with hemolysis during combination therapy of interferon and ribavirin for chronic hepatitis C.,"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.","[{'text': 'ribavirin', 'type': 'Chemical', 'start': 19, 'end': 28, 'mesh': 'D012254'}, {'text': 'hemolysis', 'type': 'Disease', 'start': 56, 'end': 65, 'mesh': 'D006461'}, {'text': 'interferon', 'type': 'Chemical', 'start': 96, 'end': 106, 'mesh': 'D007372'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 111, 'end': 120, 'mesh': 'D012254'}, {'text': 'chronic hepatitis C', 'type': 'Disease', 'start': 125, 'end': 144, 'mesh': 'D019698'}, {'text': 'Hemolytic anemia', 'type': 'Disease', 'start': 158, 'end': 174, 'mesh': 'D000743'}, {'text': 'interferon', 'type': 'Chemical', 'start': 240, 'end': 250, 'mesh': 'D007372'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 255, 'end': 264, 'mesh': 'D012254'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 277, 'end': 286, 'mesh': 'D012254'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 295, 'end': 311, 'mesh': 'D000743'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 447, 'end': 456, 'mesh': 'D012254'}, {'text': 'hemolysis', 'type': 'Disease', 'start': 484, 'end': 493, 'mesh': 'D006461'}, {'text': 'anemia', 'type': 'Disease', 'start': 657, 'end': 663, 'mesh': 'D000740'}, {'text': 'anemia', 'type': 'Disease', 'start': 698, 'end': 704, 'mesh': 'D000740'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 792, 'end': 801, 'mesh': 'D012254'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 839, 'end': 848, 'mesh': 'D012254'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 983, 'end': 992, 'mesh': 'D012254'}, {'text': 'anemia', 'type': 'Disease', 'start': 1090, 'end': 1096, 'mesh': 'D000740'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 1206, 'end': 1215, 'mesh': 'D012254'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 1534, 'end': 1543, 'mesh': 'D012254'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 1718, 'end': 1727, 'mesh': 'D012254'}]"
+832,15075188,Increased expression and apical targeting of renal ENaC subunits in puromycin aminonucleoside-induced nephrotic syndrome in rats.,"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.","[{'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 68, 'end': 93, 'mesh': 'D011692'}, {'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 102, 'end': 120, 'mesh': 'D009404'}, {'text': 'Nephrotic syndrome', 'type': 'Disease', 'start': 130, 'end': 148, 'mesh': 'D009404'}, {'text': 'sodium', 'type': 'Chemical', 'start': 173, 'end': 179, 'mesh': 'D012964'}, {'text': 'edema', 'type': 'Disease', 'start': 206, 'end': 211, 'mesh': 'D004487'}, {'text': 'sodium', 'type': 'Chemical', 'start': 266, 'end': 272, 'mesh': 'D012964'}, {'text': 'Na', 'type': 'Chemical', 'start': 334, 'end': 336, 'mesh': 'D012964'}, {'text': 'sodium', 'type': 'Chemical', 'start': 411, 'end': 417, 'mesh': 'D012964'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 476, 'end': 501, 'mesh': 'D011692'}, {'text': 'PAN', 'type': 'Chemical', 'start': 503, 'end': 506, 'mesh': 'D011692'}, {'text': 'PAN', 'type': 'Chemical', 'start': 586, 'end': 589, 'mesh': 'D011692'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 620, 'end': 631, 'mesh': 'D011507'}, {'text': 'hypoalbuminemia', 'type': 'Disease', 'start': 633, 'end': 648, 'mesh': 'D034141'}, {'text': 'sodium', 'type': 'Chemical', 'start': 668, 'end': 674, 'mesh': 'D012964'}, {'text': 'ascites', 'type': 'Disease', 'start': 700, 'end': 707, 'mesh': 'D001201'}, {'text': 'PAN', 'type': 'Chemical', 'start': 1413, 'end': 1416, 'mesh': 'D011692'}, {'text': 'Na', 'type': 'Chemical', 'start': 1531, 'end': 1533, 'mesh': 'D012964'}, {'text': 'H', 'type': 'Chemical', 'start': 1537, 'end': 1538, 'mesh': 'D006859'}, {'text': 'Na', 'type': 'Chemical', 'start': 1567, 'end': 1569, 'mesh': 'D012964'}, {'text': 'K', 'type': 'Chemical', 'start': 1573, 'end': 1574, 'mesh': 'D011188'}, {'text': 'Cl', 'type': 'Chemical', 'start': 1579, 'end': 1581, 'mesh': 'D002713'}, {'text': 'thiazide', 'type': 'Chemical', 'start': 1612, 'end': 1620, 'mesh': 'D049971'}, {'text': 'Na', 'type': 'Chemical', 'start': 1631, 'end': 1633, 'mesh': 'D012964'}, {'text': 'Cl', 'type': 'Chemical', 'start': 1637, 'end': 1639, 'mesh': 'D002713'}, {'text': 'Na', 'type': 'Chemical', 'start': 1734, 'end': 1736, 'mesh': 'D012964'}, {'text': 'K', 'type': 'Chemical', 'start': 1737, 'end': 1738, 'mesh': 'D011188'}, {'text': 'sodium', 'type': 'Chemical', 'start': 2017, 'end': 2023, 'mesh': 'D012964'}, {'text': 'PAN', 'type': 'Chemical', 'start': 2050, 'end': 2053, 'mesh': 'D011692'}, {'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 2062, 'end': 2080, 'mesh': 'D009404'}, {'text': 'Na', 'type': 'Chemical', 'start': 2131, 'end': 2133, 'mesh': 'D012964'}, {'text': 'K', 'type': 'Chemical', 'start': 2134, 'end': 2135, 'mesh': 'D011188'}, {'text': 'sodium', 'type': 'Chemical', 'start': 2183, 'end': 2189, 'mesh': 'D012964'}]"
+833,14745746,Does hormone therapy for the treatment of breast cancer have a detrimental effect on memory and cognition? A pilot study.,"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.","[{'text': 'breast cancer', 'type': 'Disease', 'start': 42, 'end': 55, 'mesh': 'D001943'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 176, 'end': 189, 'mesh': 'D001943'}, {'text': 'anastrozole', 'type': 'Chemical', 'start': 257, 'end': 268, 'mesh': 'C090450'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 270, 'end': 279, 'mesh': 'D013629'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 341, 'end': 354, 'mesh': 'D001943'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 896, 'end': 909, 'mesh': 'D001943'}, {'text': 'oestrogen', 'type': 'Chemical', 'start': 967, 'end': 976, 'mesh': 'D004967'}]"
+834,11208990,Association of nitric oxide production and apoptosis in a model of experimental nephropathy.,"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.","[{'text': 'nitric oxide', 'type': 'Chemical', 'start': 15, 'end': 27, 'mesh': 'D009569'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 80, 'end': 91, 'mesh': 'D007674'}, {'text': 'nitric oxide', 'type': 'Chemical', 'start': 144, 'end': 156, 'mesh': 'D009569'}, {'text': 'NO', 'type': 'Chemical', 'start': 158, 'end': 160, 'mesh': 'D009569'}, {'text': 'NO', 'type': 'Chemical', 'start': 275, 'end': 277, 'mesh': 'D009569'}, {'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 341, 'end': 359, 'mesh': 'D009404'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 393, 'end': 403, 'mesh': 'D004317'}, {'text': 'ADR', 'type': 'Chemical', 'start': 405, 'end': 408, 'mesh': 'D004317'}, {'text': 'NO', 'type': 'Chemical', 'start': 442, 'end': 444, 'mesh': 'D009569'}, {'text': 'nitrite', 'type': 'Chemical', 'start': 479, 'end': 486, 'mesh': 'D009573'}, {'text': 'ADR', 'type': 'Chemical', 'start': 658, 'end': 661, 'mesh': 'D004317'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 670, 'end': 681, 'mesh': 'D007674'}, {'text': 'aminoguanidine', 'type': 'Chemical', 'start': 797, 'end': 811, 'mesh': 'C004479'}, {'text': 'AG', 'type': 'Chemical', 'start': 813, 'end': 815, 'mesh': 'C004479'}, {'text': 'NO', 'type': 'Chemical', 'start': 860, 'end': 862, 'mesh': 'D009569'}, {'text': 'ADR', 'type': 'Chemical', 'start': 1031, 'end': 1034, 'mesh': 'D004317'}, {'text': 'mesangial proliferation', 'type': 'Disease', 'start': 1059, 'end': 1082, 'mesh': 'C537346'}, {'text': 'tubulointerstitial inflammation', 'type': 'Disease', 'start': 1092, 'end': 1123, 'mesh': 'D009395'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1170, 'end': 1181, 'mesh': 'D011507'}, {'text': 'nitrite', 'type': 'Chemical', 'start': 1243, 'end': 1250, 'mesh': 'D009573'}, {'text': 'ADR', 'type': 'Chemical', 'start': 1294, 'end': 1297, 'mesh': 'D004317'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1298, 'end': 1309, 'mesh': 'D007674'}, {'text': 'phenylephrine', 'type': 'Chemical', 'start': 1340, 'end': 1353, 'mesh': 'D010656'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 1358, 'end': 1371, 'mesh': 'D000109'}, {'text': 'ADR', 'type': 'Chemical', 'start': 1425, 'end': 1428, 'mesh': 'D004317'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1429, 'end': 1440, 'mesh': 'D007674'}, {'text': 'ADR', 'type': 'Chemical', 'start': 1504, 'end': 1507, 'mesh': 'D004317'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1508, 'end': 1519, 'mesh': 'D007674'}, {'text': 'AG', 'type': 'Chemical', 'start': 1733, 'end': 1735, 'mesh': 'C004479'}, {'text': 'nitrite', 'type': 'Chemical', 'start': 1816, 'end': 1823, 'mesh': 'D009573'}, {'text': 'NO', 'type': 'Chemical', 'start': 1913, 'end': 1915, 'mesh': 'D009569'}, {'text': 'ADR', 'type': 'Chemical', 'start': 1971, 'end': 1974, 'mesh': 'D004317'}, {'text': 'nephrosis', 'type': 'Disease', 'start': 1983, 'end': 1992, 'mesh': 'D009401'}]"
+835,9201797,"The attenuating effect of carteolol hydrochloride, a beta-adrenoceptor antagonist, on neuroleptic-induced catalepsy in rats.","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.","[{'text': 'carteolol hydrochloride', 'type': 'Chemical', 'start': 26, 'end': 49, 'mesh': 'D002354'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 106, 'end': 115, 'mesh': 'D002375'}, {'text': 'akathisia', 'type': 'Disease', 'start': 206, 'end': 215, 'mesh': 'D017109'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 317, 'end': 326, 'mesh': 'D002375'}, {'text': 'akathisia', 'type': 'Disease', 'start': 458, 'end': 467, 'mesh': 'D017109'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 508, 'end': 517, 'mesh': 'D002375'}, {'text': 'akathisia', 'type': 'Disease', 'start': 577, 'end': 586, 'mesh': 'D017109'}, {'text': 'carteolol', 'type': 'Chemical', 'start': 614, 'end': 623, 'mesh': 'D002354'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 660, 'end': 671, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 680, 'end': 689, 'mesh': 'D002375'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 751, 'end': 762, 'mesh': 'D011433'}, {'text': 'biperiden', 'type': 'Chemical', 'start': 767, 'end': 776, 'mesh': 'D001712'}, {'text': 'Carteolol', 'type': 'Chemical', 'start': 812, 'end': 821, 'mesh': 'D002354'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 834, 'end': 845, 'mesh': 'D011433'}, {'text': 'biperiden', 'type': 'Chemical', 'start': 850, 'end': 859, 'mesh': 'D001712'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 875, 'end': 886, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 895, 'end': 904, 'mesh': 'D002375'}, {'text': 'carteolol', 'type': 'Chemical', 'start': 931, 'end': 940, 'mesh': 'D002354'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 974, 'end': 985, 'mesh': 'D011433'}, {'text': 'biperiden', 'type': 'Chemical', 'start': 1015, 'end': 1024, 'mesh': 'D001712'}, {'text': 'Carteolol', 'type': 'Chemical', 'start': 1026, 'end': 1035, 'mesh': 'D002354'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1063, 'end': 1071, 'mesh': 'D004298'}, {'text': 'hyperlocomotion', 'type': 'Disease', 'start': 1133, 'end': 1148, 'mesh': 'D009069'}, {'text': 'Carteolol', 'type': 'Chemical', 'start': 1158, 'end': 1167, 'mesh': 'D002354'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1213, 'end': 1224, 'mesh': 'D006220'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 1228, 'end': 1239, 'mesh': 'D001058'}, {'text': 'carteolol', 'type': 'Chemical', 'start': 1304, 'end': 1313, 'mesh': 'D002354'}, {'text': '5-hydroxytryptophan', 'type': 'Chemical', 'start': 1440, 'end': 1459, 'mesh': 'D006916'}, {'text': 'carteolol', 'type': 'Chemical', 'start': 1498, 'end': 1507, 'mesh': 'D002354'}, {'text': 'physostigmine', 'type': 'Chemical', 'start': 1524, 'end': 1537, 'mesh': 'D010830'}, {'text': 'carteolol', 'type': 'Chemical', 'start': 1601, 'end': 1610, 'mesh': 'D002354'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1620, 'end': 1631, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 1640, 'end': 1649, 'mesh': 'D002375'}, {'text': 'akathisia', 'type': 'Disease', 'start': 1750, 'end': 1759, 'mesh': 'D017109'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1846, 'end': 1854, 'mesh': 'D004298'}]"
+836,8267029,Penicillamine-induced rapidly progressive glomerulonephritis in a patient with rheumatoid arthritis.,"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.","[{'text': 'Penicillamine', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'D010396'}, {'text': 'glomerulonephritis', 'type': 'Disease', 'start': 42, 'end': 60, 'mesh': 'D005921'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 79, 'end': 99, 'mesh': 'D001172'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 126, 'end': 146, 'mesh': 'D001172'}, {'text': 'glomerulonephritis', 'type': 'Disease', 'start': 177, 'end': 195, 'mesh': 'D005921'}, {'text': 'RPGN', 'type': 'Disease', 'start': 197, 'end': 201, 'mesh': 'D005921'}, {'text': 'D-penicillamine', 'type': 'Chemical', 'start': 221, 'end': 236, 'mesh': 'D010396'}, {'text': 'glomerulonephritis', 'type': 'Disease', 'start': 298, 'end': 316, 'mesh': 'D005921'}, {'text': 'steroid', 'type': 'Chemical', 'start': 572, 'end': 579, 'mesh': 'D013256'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 603, 'end': 619, 'mesh': 'D003520'}, {'text': 'antiplatelet agents', 'type': 'Chemical', 'start': 624, 'end': 643, 'mesh': 'D010975'}, {'text': 'RPGN', 'type': 'Disease', 'start': 729, 'end': 733, 'mesh': 'D005921'}, {'text': 'D-penicillamine', 'type': 'Chemical', 'start': 751, 'end': 766, 'mesh': 'D010396'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 878, 'end': 889, 'mesh': 'D011507'}, {'text': 'D-penicillamine', 'type': 'Chemical', 'start': 939, 'end': 954, 'mesh': 'D010396'}]"
+837,2528969,"Nature, time course and dose dependence of zidovudine-related side effects: results from the Multicenter Canadian Azidothymidine Trial.","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)","[{'text': 'zidovudine', 'type': 'Chemical', 'start': 43, 'end': 53, 'mesh': 'D015215'}, {'text': 'Azidothymidine', 'type': 'Chemical', 'start': 114, 'end': 128, 'mesh': 'D015215'}, {'text': 'zidovudine', 'type': 'Chemical', 'start': 199, 'end': 209, 'mesh': 'D015215'}, {'text': 'HIV disease', 'type': 'Disease', 'start': 460, 'end': 471, 'mesh': 'D015658'}, {'text': 'zidovudine', 'type': 'Chemical', 'start': 541, 'end': 551, 'mesh': 'D015215'}, {'text': 'nausea', 'type': 'Disease', 'start': 1034, 'end': 1040, 'mesh': 'D009325'}, {'text': 'fatigue', 'type': 'Disease', 'start': 1048, 'end': 1055, 'mesh': 'D005221'}, {'text': 'headache', 'type': 'Disease', 'start': 1066, 'end': 1074, 'mesh': 'D006261'}, {'text': 'megaloblastosis', 'type': 'Disease', 'start': 1714, 'end': 1729, 'mesh': '-1'}]"
+838,384871,Bilateral optic neuropathy due to combined ethambutol and isoniazid treatment.,"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.","[{'text': 'Bilateral optic neuropathy', 'type': 'Disease', 'start': 0, 'end': 26, 'mesh': 'D009901'}, {'text': 'ethambutol', 'type': 'Chemical', 'start': 43, 'end': 53, 'mesh': 'D004977'}, {'text': 'isoniazid', 'type': 'Chemical', 'start': 58, 'end': 67, 'mesh': 'D007538'}, {'text': 'ethambutol', 'type': 'Chemical', 'start': 195, 'end': 205, 'mesh': 'D004977'}, {'text': 'isoniazid', 'type': 'Chemical', 'start': 210, 'end': 219, 'mesh': 'D007538'}, {'text': 'bilateral retrobulbar neuropathy', 'type': 'Disease', 'start': 235, 'end': 267, 'mesh': 'D009901'}, {'text': 'scotoma', 'type': 'Disease', 'start': 314, 'end': 321, 'mesh': 'D012607'}, {'text': 'Ethambutol', 'type': 'Chemical', 'start': 333, 'end': 343, 'mesh': 'D004977'}, {'text': 'Isoniazid', 'type': 'Chemical', 'start': 414, 'end': 423, 'mesh': 'D007538'}, {'text': 'toxicity', 'type': 'Disease', 'start': 532, 'end': 540, 'mesh': 'D064420'}, {'text': 'ethambutol', 'type': 'Chemical', 'start': 548, 'end': 558, 'mesh': 'D004977'}, {'text': 'ethambutol', 'type': 'Chemical', 'start': 618, 'end': 628, 'mesh': 'D004977'}, {'text': 'isoniazid', 'type': 'Chemical', 'start': 633, 'end': 642, 'mesh': 'D007538'}]"
+839,133615,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.,"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.","[{'text': 'blood coagulation', 'type': 'Disease', 'start': 26, 'end': 43, 'mesh': 'D001778'}, {'text': 'Thromboembolic', 'type': 'Disease', 'start': 50, 'end': 64, 'mesh': 'D013923'}, {'text': 'oral contraceptive', 'type': 'Chemical', 'start': 92, 'end': 110, 'mesh': 'D003276'}, {'text': 'blood coagulation', 'type': 'Disease', 'start': 161, 'end': 178, 'mesh': 'D001778'}, {'text': 'oral contraceptives', 'type': 'Chemical', 'start': 343, 'end': 362, 'mesh': 'D003276'}, {'text': 'blood coagulation', 'type': 'Disease', 'start': 449, 'end': 466, 'mesh': 'D001778'}, {'text': 'blood coagulation', 'type': 'Disease', 'start': 653, 'end': 670, 'mesh': 'D001778'}, {'text': 'hypercoagulability', 'type': 'Disease', 'start': 692, 'end': 710, 'mesh': 'D019851'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 919, 'end': 940, 'mesh': 'D009203'}, {'text': 'retinopathy', 'type': 'Disease', 'start': 1046, 'end': 1057, 'mesh': 'D012164'}, {'text': 'thrombophlebitis', 'type': 'Disease', 'start': 1115, 'end': 1131, 'mesh': 'D013924'}, {'text': 'thrombophlebitis', 'type': 'Disease', 'start': 1189, 'end': 1205, 'mesh': 'D013924'}, {'text': 'thromboembolic episodes', 'type': 'Disease', 'start': 1380, 'end': 1403, 'mesh': 'D013923'}, {'text': 'oral contraceptive', 'type': 'Chemical', 'start': 1551, 'end': 1569, 'mesh': 'D003276'}]"
+840,17263743,Cardiac arrest in a child with cerebral palsy undergoing sevoflurane induction of anesthesia after preoperative clonidine.,"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.","[{'text': 'Cardiac arrest', 'type': 'Disease', 'start': 0, 'end': 14, 'mesh': 'D006323'}, {'text': 'cerebral palsy', 'type': 'Disease', 'start': 31, 'end': 45, 'mesh': 'D002547'}, {'text': 'sevoflurane', 'type': 'Chemical', 'start': 57, 'end': 68, 'mesh': 'C009250'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 112, 'end': 121, 'mesh': 'D003000'}, {'text': 'Clonidine', 'type': 'Chemical', 'start': 123, 'end': 132, 'mesh': 'D003000'}, {'text': 'cerebral palsy', 'type': 'Disease', 'start': 283, 'end': 297, 'mesh': 'D002547'}, {'text': 'seizure disorder', 'type': 'Disease', 'start': 302, 'end': 318, 'mesh': 'D004827'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 330, 'end': 339, 'mesh': 'D003000'}, {'text': 'restlessness', 'type': 'Disease', 'start': 344, 'end': 356, 'mesh': 'D011595'}, {'text': 'baclofen', 'type': 'Chemical', 'start': 391, 'end': 399, 'mesh': 'D001418'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 503, 'end': 512, 'mesh': 'D003000'}, {'text': 'anxiety', 'type': 'Disease', 'start': 572, 'end': 579, 'mesh': 'D001008'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 635, 'end': 646, 'mesh': 'D001919'}, {'text': 'hypotension', 'type': 'Disease', 'start': 651, 'end': 662, 'mesh': 'D007022'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 729, 'end': 738, 'mesh': 'D003000'}, {'text': 'cardiac arrest', 'type': 'Disease', 'start': 750, 'end': 764, 'mesh': 'D006323'}]"
+841,17241657,"Effects of UMB24 and (+/-)-SM 21, putative sigma2-preferring antagonists, on behavioral toxic and stimulant effects of cocaine in mice.","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.","[{'text': 'UMB24', 'type': 'Chemical', 'start': 11, 'end': 16, 'mesh': 'C519696'}, {'text': 'SM 21', 'type': 'Chemical', 'start': 27, 'end': 32, 'mesh': 'C107044'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 119, 'end': 126, 'mesh': 'D003042'}, {'text': 'convulsive', 'type': 'Disease', 'start': 221, 'end': 231, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 288, 'end': 295, 'mesh': 'D003042'}, {'text': 'UMB24', 'type': 'Chemical', 'start': 493, 'end': 498, 'mesh': 'C519696'}, {'text': '1-(2-phenethyl)-4-(2-pyridyl)-piperazine', 'type': 'Chemical', 'start': 500, 'end': 540, 'mesh': 'C519696'}, {'text': 'SM 21', 'type': 'Chemical', 'start': 552, 'end': 557, 'mesh': 'C107044'}, {'text': '3alpha-tropanyl-2-(4-chorophenoxy)butyrate', 'type': 'Chemical', 'start': 559, 'end': 601, 'mesh': 'C107044'}, {'text': 'UMB24', 'type': 'Chemical', 'start': 687, 'end': 692, 'mesh': 'C519696'}, {'text': 'SM 21', 'type': 'Chemical', 'start': 703, 'end': 708, 'mesh': 'C107044'}, {'text': 'UMB24', 'type': 'Chemical', 'start': 836, 'end': 841, 'mesh': 'C519696'}, {'text': 'SM 21', 'type': 'Chemical', 'start': 851, 'end': 856, 'mesh': 'C107044'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 882, 'end': 889, 'mesh': 'D003042'}, {'text': 'convulsions', 'type': 'Disease', 'start': 898, 'end': 909, 'mesh': 'D012640'}, {'text': 'SM 21', 'type': 'Chemical', 'start': 984, 'end': 989, 'mesh': 'C107044'}, {'text': 'UMB24', 'type': 'Chemical', 'start': 1068, 'end': 1073, 'mesh': 'C519696'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1234, 'end': 1241, 'mesh': 'D003042'}]"
+842,14982270,Methimazole-induced cholestatic jaundice.,"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.","[{'text': 'Methimazole', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D008713'}, {'text': 'cholestatic jaundice', 'type': 'Disease', 'start': 20, 'end': 40, 'mesh': 'D041781'}, {'text': 'Methimazole', 'type': 'Chemical', 'start': 42, 'end': 53, 'mesh': 'D008713'}, {'text': 'jaundice', 'type': 'Disease', 'start': 150, 'end': 158, 'mesh': 'D007565'}, {'text': 'itching', 'type': 'Disease', 'start': 163, 'end': 170, 'mesh': 'D011537'}, {'text': 'methimazole', 'type': 'Chemical', 'start': 195, 'end': 206, 'mesh': 'D008713'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 223, 'end': 234, 'mesh': 'D011433'}, {'text': 'hyperthyroidism', 'type': 'Disease', 'start': 264, 'end': 279, 'mesh': 'D006980'}, {'text': 'jaundice', 'type': 'Disease', 'start': 356, 'end': 364, 'mesh': 'D007565'}, {'text': 'icterus', 'type': 'Disease', 'start': 476, 'end': 483, 'mesh': 'D007565'}, {'text': 'pruritus', 'type': 'Disease', 'start': 485, 'end': 493, 'mesh': 'D011537'}, {'text': 'hyperbilirubinemia', 'type': 'Disease', 'start': 499, 'end': 517, 'mesh': 'D006932'}, {'text': 'Methimazole', 'type': 'Chemical', 'start': 561, 'end': 572, 'mesh': 'D008713'}, {'text': 'cholestasis', 'type': 'Disease', 'start': 581, 'end': 592, 'mesh': 'D002779'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 612, 'end': 623, 'mesh': 'D011433'}, {'text': 'bilirubin', 'type': 'Chemical', 'start': 705, 'end': 714, 'mesh': 'D001663'}, {'text': 'methimazole', 'type': 'Chemical', 'start': 757, 'end': 768, 'mesh': 'D008713'}, {'text': 'cholestatic jaundice', 'type': 'Disease', 'start': 865, 'end': 885, 'mesh': 'D041781'}, {'text': 'methimazole', 'type': 'Chemical', 'start': 997, 'end': 1008, 'mesh': 'D008713'}]"
+843,12911170,Ciprofloxacin-induced acute interstitial nephritis and autoimmune hemolytic anemia.,"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.","[{'text': 'Ciprofloxacin', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'D002939'}, {'text': 'interstitial nephritis', 'type': 'Disease', 'start': 28, 'end': 50, 'mesh': 'D009395'}, {'text': 'autoimmune hemolytic anemia', 'type': 'Disease', 'start': 55, 'end': 82, 'mesh': 'D000744'}, {'text': 'Ciprofloxacin', 'type': 'Chemical', 'start': 84, 'end': 97, 'mesh': 'D002939'}, {'text': 'interstitial nephritis', 'type': 'Disease', 'start': 154, 'end': 176, 'mesh': 'D009395'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 181, 'end': 197, 'mesh': 'D000743'}, {'text': 'ciprofloxacin', 'type': 'Chemical', 'start': 293, 'end': 306, 'mesh': 'D002939'}, {'text': 'interstitial nephritis', 'type': 'Disease', 'start': 315, 'end': 337, 'mesh': 'D009395'}, {'text': 'autoimmune hemolytic anemia', 'type': 'Disease', 'start': 342, 'end': 369, 'mesh': 'D000744'}, {'text': 'Hemolytic anemia', 'type': 'Disease', 'start': 371, 'end': 387, 'mesh': 'D000743'}, {'text': 'steroid', 'type': 'Chemical', 'start': 439, 'end': 446, 'mesh': 'D013256'}, {'text': 'interstitial nephritis', 'type': 'Disease', 'start': 477, 'end': 499, 'mesh': 'D009395'}, {'text': 'end-stage renal disease', 'type': 'Disease', 'start': 543, 'end': 566, 'mesh': 'D007676'}]"
+844,11195262,Contribution of sodium valproate to the syndrome of inappropriate secretion of antidiuretic hormone.,"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.","[{'text': 'sodium valproate', 'type': 'Chemical', 'start': 16, 'end': 32, 'mesh': 'D014635'}, {'text': 'syndrome of inappropriate secretion of antidiuretic hormone', 'type': 'Disease', 'start': 40, 'end': 99, 'mesh': 'D007177'}, {'text': 'sodium valproate', 'type': 'Chemical', 'start': 162, 'end': 178, 'mesh': 'D014635'}, {'text': 'VPA', 'type': 'Chemical', 'start': 180, 'end': 183, 'mesh': 'D014635'}, {'text': 'syndrome of inappropriate secretion of antidiuretic hormone', 'type': 'Disease', 'start': 220, 'end': 279, 'mesh': 'D007177'}, {'text': 'SIADH', 'type': 'Disease', 'start': 281, 'end': 286, 'mesh': 'D007177'}, {'text': 'VPA', 'type': 'Chemical', 'start': 308, 'end': 311, 'mesh': 'D014635'}, {'text': 'tonic-clonic convulsions', 'type': 'Disease', 'start': 352, 'end': 376, 'mesh': 'D004830'}, {'text': 'VPA', 'type': 'Chemical', 'start': 423, 'end': 426, 'mesh': 'D014635'}, {'text': 'zonisamide', 'type': 'Chemical', 'start': 432, 'end': 442, 'mesh': 'C022189'}, {'text': 'sodium', 'type': 'Chemical', 'start': 454, 'end': 460, 'mesh': 'D012964'}, {'text': 'SIADH', 'type': 'Disease', 'start': 515, 'end': 520, 'mesh': 'D007177'}, {'text': 'weakness of the central nervous system', 'type': 'Disease', 'start': 578, 'end': 616, 'mesh': 'D002493'}, {'text': 'VPA', 'type': 'Chemical', 'start': 653, 'end': 656, 'mesh': 'D014635'}]"
+845,10728962,Vasopressin in the treatment of milrinone-induced hypotension in severe heart failure.,"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.","[{'text': 'Vasopressin', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D014667'}, {'text': 'milrinone', 'type': 'Chemical', 'start': 32, 'end': 41, 'mesh': 'D020105'}, {'text': 'hypotension', 'type': 'Disease', 'start': 50, 'end': 61, 'mesh': 'D007022'}, {'text': 'heart failure', 'type': 'Disease', 'start': 72, 'end': 85, 'mesh': 'D006333'}, {'text': 'milrinone', 'type': 'Chemical', 'start': 135, 'end': 144, 'mesh': 'D020105'}, {'text': 'heart failure', 'type': 'Disease', 'start': 172, 'end': 185, 'mesh': 'D006333'}, {'text': 'hypotension', 'type': 'Disease', 'start': 247, 'end': 258, 'mesh': 'D007022'}, {'text': 'heart failure', 'type': 'Disease', 'start': 291, 'end': 304, 'mesh': 'D006333'}, {'text': 'hypotension', 'type': 'Disease', 'start': 310, 'end': 321, 'mesh': 'D007022'}, {'text': 'milrinone', 'type': 'Chemical', 'start': 343, 'end': 352, 'mesh': 'D020105'}, {'text': 'vasopressin', 'type': 'Chemical', 'start': 367, 'end': 378, 'mesh': 'D014667'}, {'text': 'milrinone', 'type': 'Chemical', 'start': 446, 'end': 455, 'mesh': 'D020105'}]"
+846,7647582,Halogenated anesthetics form liver adducts and antigens that cross-react with halothane-induced antibodies.,"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.","[{'text': 'halothane', 'type': 'Chemical', 'start': 78, 'end': 87, 'mesh': 'D006221'}, {'text': 'enflurane', 'type': 'Chemical', 'start': 137, 'end': 146, 'mesh': 'D004737'}, {'text': 'isoflurane', 'type': 'Chemical', 'start': 151, 'end': 161, 'mesh': 'D007530'}, {'text': 'hepatic injury', 'type': 'Disease', 'start': 206, 'end': 220, 'mesh': 'D056486'}, {'text': 'halothane', 'type': 'Chemical', 'start': 267, 'end': 276, 'mesh': 'D006221'}, {'text': 'Halothane', 'type': 'Chemical', 'start': 278, 'end': 287, 'mesh': 'D006221'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 288, 'end': 297, 'mesh': 'D056486'}, {'text': 'trifluoroacetyl', 'type': 'Chemical', 'start': 413, 'end': 428, 'mesh': 'D014269'}, {'text': 'halothane', 'type': 'Chemical', 'start': 458, 'end': 467, 'mesh': 'D006221'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 468, 'end': 477, 'mesh': 'D056486'}, {'text': 'enflurane', 'type': 'Chemical', 'start': 551, 'end': 560, 'mesh': 'D004737'}, {'text': 'isoflurane', 'type': 'Chemical', 'start': 565, 'end': 575, 'mesh': 'D007530'}, {'text': 'hypersensitivity', 'type': 'Disease', 'start': 585, 'end': 601, 'mesh': 'D004342'}, {'text': 'halothane', 'type': 'Chemical', 'start': 613, 'end': 622, 'mesh': 'D006221'}, {'text': 'halothane', 'type': 'Chemical', 'start': 700, 'end': 709, 'mesh': 'D006221'}, {'text': 'enflurane', 'type': 'Chemical', 'start': 739, 'end': 748, 'mesh': 'D004737'}, {'text': 'isoflurane', 'type': 'Chemical', 'start': 753, 'end': 763, 'mesh': 'D007530'}, {'text': 'Enflurane', 'type': 'Chemical', 'start': 852, 'end': 861, 'mesh': 'D004737'}, {'text': 'enflurane', 'type': 'Chemical', 'start': 1228, 'end': 1237, 'mesh': 'D004737'}, {'text': 'isoflurane', 'type': 'Chemical', 'start': 1245, 'end': 1255, 'mesh': 'D007530'}, {'text': 'hypersensitivity', 'type': 'Disease', 'start': 1272, 'end': 1288, 'mesh': 'D004342'}, {'text': 'halothane', 'type': 'Chemical', 'start': 1318, 'end': 1327, 'mesh': 'D006221'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 1328, 'end': 1337, 'mesh': 'D056486'}, {'text': 'halothane', 'type': 'Chemical', 'start': 1368, 'end': 1377, 'mesh': 'D006221'}]"
+847,4090988,Induction by paracetamol of bladder and liver tumours in the rat. Effects on hepatocyte fine structure.,"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.","[{'text': 'paracetamol', 'type': 'Chemical', 'start': 13, 'end': 24, 'mesh': 'D000082'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 201, 'end': 212, 'mesh': 'D000082'}, {'text': 'Papillomas', 'type': 'Disease', 'start': 543, 'end': 553, 'mesh': 'D010212'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 617, 'end': 628, 'mesh': 'D000082'}, {'text': 'bladder carcinomas', 'type': 'Disease', 'start': 665, 'end': 683, 'mesh': 'D001749'}, {'text': 'bladder tumours', 'type': 'Disease', 'start': 716, 'end': 731, 'mesh': 'D001749'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 825, 'end': 836, 'mesh': 'D000082'}, {'text': 'hyperplasia', 'type': 'Disease', 'start': 860, 'end': 871, 'mesh': 'D006965'}, {'text': 'bladder calculi', 'type': 'Disease', 'start': 945, 'end': 960, 'mesh': 'D001744'}, {'text': 'tumours', 'type': 'Disease', 'start': 977, 'end': 984, 'mesh': 'D009369'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 1029, 'end': 1040, 'mesh': 'D000082'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 1096, 'end': 1107, 'mesh': 'D000082'}, {'text': 'hepatocarcinogens', 'type': 'Disease', 'start': 1241, 'end': 1258, 'mesh': 'D008113'}]"
+848,4038130,Rat extraocular muscle regeneration. Repair of local anesthetic-induced damage.,"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.","[{'text': 'bupivacaine hydrochloride', 'type': 'Chemical', 'start': 150, 'end': 175, 'mesh': 'D002045'}, {'text': 'mepivacaine hydrochloride', 'type': 'Chemical', 'start': 182, 'end': 207, 'mesh': 'D008619'}, {'text': 'lidocaine hydrochloride', 'type': 'Chemical', 'start': 218, 'end': 241, 'mesh': 'D008012'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 257, 'end': 268, 'mesh': 'D004837'}, {'text': 'Muscle degeneration', 'type': 'Disease', 'start': 453, 'end': 472, 'mesh': 'D009135'}, {'text': 'muscle damage', 'type': 'Disease', 'start': 546, 'end': 559, 'mesh': 'D009135'}, {'text': 'mepivacaine', 'type': 'Chemical', 'start': 639, 'end': 650, 'mesh': 'D008619'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 655, 'end': 664, 'mesh': 'D008012'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 670, 'end': 681, 'mesh': 'D004837'}, {'text': 'diplopia', 'type': 'Disease', 'start': 750, 'end': 758, 'mesh': 'D004172'}]"
+849,2907585,Reversal of neuroleptic-induced catalepsy by novel aryl-piperazine anxiolytic drugs.,"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.","[{'text': 'catalepsy', 'type': 'Disease', 'start': 32, 'end': 41, 'mesh': 'D002375'}, {'text': 'aryl-piperazine', 'type': 'Chemical', 'start': 51, 'end': 66, 'mesh': '-1'}, {'text': 'buspirone', 'type': 'Chemical', 'start': 112, 'end': 121, 'mesh': 'D002065'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 132, 'end': 141, 'mesh': 'D002375'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 153, 'end': 164, 'mesh': 'D006220'}, {'text': 'aryl-piperazine', 'type': 'Chemical', 'start': 178, 'end': 193, 'mesh': '-1'}, {'text': 'buspirone', 'type': 'Chemical', 'start': 207, 'end': 216, 'mesh': 'D002065'}, {'text': '5-hydroxytryptaminergic agonists', 'type': 'Chemical', 'start': 227, 'end': 259, 'mesh': 'D058825'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 301, 'end': 312, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 321, 'end': 330, 'mesh': 'D002375'}, {'text': '5-hydroxytryptamine', 'type': 'Chemical', 'start': 369, 'end': 388, 'mesh': 'D012701'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 422, 'end': 431, 'mesh': 'D002375'}, {'text': '5-HT', 'type': 'Chemical', 'start': 463, 'end': 467, 'mesh': 'D012701'}, {'text': '5-HT', 'type': 'Chemical', 'start': 549, 'end': 553, 'mesh': 'D012701'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 610, 'end': 619, 'mesh': 'D002375'}]"
+850,2894433,Diazepam facilitates reflex bradycardia in conscious rats.,"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.","[{'text': 'Diazepam', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D003975'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 28, 'end': 39, 'mesh': 'D001919'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 74, 'end': 82, 'mesh': 'D003975'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 173, 'end': 181, 'mesh': 'D003975'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 300, 'end': 311, 'mesh': 'D001919'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 360, 'end': 370, 'mesh': 'D004837'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 441, 'end': 449, 'mesh': 'D003975'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 485, 'end': 495, 'mesh': 'D004837'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 536, 'end': 546, 'mesh': 'D004837'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 562, 'end': 573, 'mesh': 'D001919'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 588, 'end': 596, 'mesh': 'D003975'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 612, 'end': 622, 'mesh': 'D004837'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 638, 'end': 649, 'mesh': 'D001919'}, {'text': 'picrotoxin', 'type': 'Chemical', 'start': 718, 'end': 728, 'mesh': 'D010852'}, {'text': 'chloride', 'type': 'Chemical', 'start': 746, 'end': 754, 'mesh': 'D002712'}, {'text': 'benzodiazepine', 'type': 'Chemical', 'start': 804, 'end': 818, 'mesh': 'D001569'}, {'text': 'GABA', 'type': 'Chemical', 'start': 819, 'end': 823, 'mesh': 'D005680'}, {'text': 'chloride', 'type': 'Chemical', 'start': 824, 'end': 832, 'mesh': 'D002712'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 889, 'end': 897, 'mesh': 'D003975'}, {'text': 'benzodiazepine', 'type': 'Chemical', 'start': 915, 'end': 929, 'mesh': 'D001569'}, {'text': 'GABA', 'type': 'Chemical', 'start': 930, 'end': 934, 'mesh': 'D005680'}, {'text': 'chloride', 'type': 'Chemical', 'start': 935, 'end': 943, 'mesh': 'D002712'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 1030, 'end': 1041, 'mesh': 'D001919'}]"
+851,2790457,Chronic carbamazepine inhibits the development of local anesthetic seizures kindled by cocaine and lidocaine.,"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.","[{'text': 'carbamazepine', 'type': 'Chemical', 'start': 8, 'end': 21, 'mesh': 'D002220'}, {'text': 'seizures', 'type': 'Disease', 'start': 67, 'end': 75, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 87, 'end': 94, 'mesh': 'D003042'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 99, 'end': 108, 'mesh': 'D008012'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 125, 'end': 138, 'mesh': 'D002220'}, {'text': 'CBZ', 'type': 'Chemical', 'start': 140, 'end': 143, 'mesh': 'D002220'}, {'text': 'seizures', 'type': 'Disease', 'start': 183, 'end': 191, 'mesh': 'D012640'}, {'text': 'CBZ', 'type': 'Chemical', 'start': 296, 'end': 299, 'mesh': 'D002220'}, {'text': 'CBZ', 'type': 'Chemical', 'start': 329, 'end': 332, 'mesh': 'D002220'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 367, 'end': 376, 'mesh': 'D008012'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 382, 'end': 389, 'mesh': 'D003042'}, {'text': 'seizures', 'type': 'Disease', 'start': 398, 'end': 406, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 470, 'end': 478, 'mesh': 'D012640'}, {'text': 'CBZ', 'type': 'Chemical', 'start': 488, 'end': 491, 'mesh': 'D002220'}, {'text': 'seizure', 'type': 'Disease', 'start': 524, 'end': 531, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 557, 'end': 564, 'mesh': 'D003042'}, {'text': 'CBZ', 'type': 'Chemical', 'start': 586, 'end': 589, 'mesh': 'D002220'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 653, 'end': 662, 'mesh': 'D008012'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 680, 'end': 687, 'mesh': 'D003042'}, {'text': 'seizures', 'type': 'Disease', 'start': 696, 'end': 704, 'mesh': 'D012640'}, {'text': 'CBZ', 'type': 'Chemical', 'start': 733, 'end': 736, 'mesh': 'D002220'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 794, 'end': 803, 'mesh': 'D008012'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 808, 'end': 815, 'mesh': 'D003042'}, {'text': 'seizures', 'type': 'Disease', 'start': 824, 'end': 832, 'mesh': 'D012640'}, {'text': 'CBZ', 'type': 'Chemical', 'start': 862, 'end': 865, 'mesh': 'D002220'}, {'text': 'seizure', 'type': 'Disease', 'start': 890, 'end': 897, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 1015, 'end': 1023, 'mesh': 'D012640'}, {'text': 'CBZ', 'type': 'Chemical', 'start': 1099, 'end': 1102, 'mesh': 'D002220'}, {'text': 'CBZ', 'type': 'Chemical', 'start': 1230, 'end': 1233, 'mesh': 'D002220'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1295, 'end': 1302, 'mesh': 'D003042'}]"
+852,2334179,D-penicillamine in the treatment of localized scleroderma.,"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.","[{'text': 'D-penicillamine', 'type': 'Chemical', 'start': 0, 'end': 15, 'mesh': 'D010396'}, {'text': 'localized scleroderma', 'type': 'Disease', 'start': 36, 'end': 57, 'mesh': 'D012594'}, {'text': 'Localized scleroderma', 'type': 'Disease', 'start': 59, 'end': 80, 'mesh': 'D012594'}, {'text': 'localized scleroderma', 'type': 'Disease', 'start': 269, 'end': 290, 'mesh': 'D012594'}, {'text': 'localized scleroderma', 'type': 'Disease', 'start': 343, 'end': 364, 'mesh': 'D012594'}, {'text': 'D-penicillamine', 'type': 'Chemical', 'start': 387, 'end': 402, 'mesh': 'D010396'}, {'text': 'contractures', 'type': 'Disease', 'start': 750, 'end': 762, 'mesh': 'D003286'}, {'text': 'D-penicillamine', 'type': 'Chemical', 'start': 790, 'end': 805, 'mesh': 'D010396'}, {'text': 'D-Penicillamine', 'type': 'Chemical', 'start': 928, 'end': 943, 'mesh': 'D010396'}, {'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 951, 'end': 969, 'mesh': 'D009404'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1005, 'end': 1016, 'mesh': 'D011507'}, {'text': 'renal insufficiency', 'type': 'Disease', 'start': 1053, 'end': 1072, 'mesh': 'D051437'}, {'text': 'D-penicillamine', 'type': 'Chemical', 'start': 1098, 'end': 1113, 'mesh': 'D010396'}, {'text': 'localized scleroderma', 'type': 'Disease', 'start': 1150, 'end': 1171, 'mesh': 'D012594'}]"
+853,1969772,Preservation of renal blood flow during hypotension induced with fenoldopam in dogs.,"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.","[{'text': 'hypotension', 'type': 'Disease', 'start': 40, 'end': 51, 'mesh': 'D007022'}, {'text': 'fenoldopam', 'type': 'Chemical', 'start': 65, 'end': 75, 'mesh': 'D018818'}, {'text': 'hypotension', 'type': 'Disease', 'start': 129, 'end': 140, 'mesh': 'D007022'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 311, 'end': 319, 'mesh': 'D004298'}, {'text': 'DA', 'type': 'Chemical', 'start': 324, 'end': 326, 'mesh': 'D004298'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 333, 'end': 341, 'mesh': 'D004298'}, {'text': 'DA', 'type': 'Chemical', 'start': 345, 'end': 347, 'mesh': 'D004298'}, {'text': 'Fenoldopam mesylate', 'type': 'Chemical', 'start': 406, 'end': 425, 'mesh': 'D018818'}, {'text': 'fenoldopam', 'type': 'Chemical', 'start': 527, 'end': 537, 'mesh': 'D018818'}, {'text': 'hypotension', 'type': 'Disease', 'start': 562, 'end': 573, 'mesh': 'D007022'}, {'text': 'fenoldopam', 'type': 'Chemical', 'start': 853, 'end': 863, 'mesh': 'D018818'}, {'text': 'sodium', 'type': 'Chemical', 'start': 868, 'end': 874, 'mesh': 'D012964'}, {'text': 'nitroprusside', 'type': 'Chemical', 'start': 875, 'end': 888, 'mesh': 'D009599'}, {'text': 'halothane', 'type': 'Chemical', 'start': 907, 'end': 916, 'mesh': 'D006221'}, {'text': 'fenoldopam', 'type': 'Chemical', 'start': 1023, 'end': 1033, 'mesh': 'D018818'}, {'text': 'sodium', 'type': 'Chemical', 'start': 1109, 'end': 1115, 'mesh': 'D012964'}, {'text': 'nitroprusside', 'type': 'Chemical', 'start': 1116, 'end': 1129, 'mesh': 'D009599'}, {'text': 'fenoldopam', 'type': 'Chemical', 'start': 1204, 'end': 1214, 'mesh': 'D018818'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1223, 'end': 1234, 'mesh': 'D007022'}, {'text': 'sodium', 'type': 'Chemical', 'start': 1292, 'end': 1298, 'mesh': 'D012964'}, {'text': 'nitroprusside', 'type': 'Chemical', 'start': 1299, 'end': 1312, 'mesh': 'D009599'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1321, 'end': 1332, 'mesh': 'D007022'}, {'text': 'nitroprusside', 'type': 'Chemical', 'start': 1360, 'end': 1373, 'mesh': 'D009599'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1509, 'end': 1520, 'mesh': 'D007022'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1548, 'end': 1556, 'mesh': 'D004298'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1713, 'end': 1724, 'mesh': 'D007022'}]"
+854,1700207,Antiarrhythmic effects of optical isomers of cibenzoline on canine ventricular arrhythmias.,"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.","[{'text': 'cibenzoline', 'type': 'Chemical', 'start': 45, 'end': 56, 'mesh': 'C032151'}, {'text': 'ventricular arrhythmias', 'type': 'Disease', 'start': 67, 'end': 90, 'mesh': 'D001145'}, {'text': 'cibenzoline', 'type': 'Chemical', 'start': 122, 'end': 133, 'mesh': 'C032151'}, {'text': 'cibenzoline', 'type': 'Chemical', 'start': 142, 'end': 153, 'mesh': 'C032151'}, {'text': 'ventricular arrhythmia', 'type': 'Disease', 'start': 185, 'end': 207, 'mesh': 'D001145'}, {'text': 'Digitalis', 'type': 'Chemical', 'start': 216, 'end': 225, 'mesh': 'D004070'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 226, 'end': 236, 'mesh': 'D001145'}, {'text': 'Na', 'type': 'Chemical', 'start': 261, 'end': 263, 'mesh': 'D012964'}, {'text': 'ouabain', 'type': 'Chemical', 'start': 342, 'end': 349, 'mesh': 'D010042'}, {'text': 'pentobarbital', 'type': 'Chemical', 'start': 353, 'end': 366, 'mesh': 'D010424'}, {'text': 'Adrenaline arrhythmia', 'type': 'Disease', 'start': 386, 'end': 407, 'mesh': 'D001145'}, {'text': 'Ca', 'type': 'Chemical', 'start': 432, 'end': 434, 'mesh': 'D002118'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 468, 'end': 478, 'mesh': 'D004837'}, {'text': 'halothane', 'type': 'Chemical', 'start': 491, 'end': 500, 'mesh': 'D006221'}, {'text': 'cibenzoline', 'type': 'Chemical', 'start': 545, 'end': 556, 'mesh': 'C032151'}, {'text': 'digitalis', 'type': 'Chemical', 'start': 568, 'end': 577, 'mesh': 'D004070'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 583, 'end': 593, 'mesh': 'D004837'}, {'text': 'arrhythmias', 'type': 'Disease', 'start': 602, 'end': 613, 'mesh': 'D001145'}, {'text': 'cibenzoline', 'type': 'Chemical', 'start': 680, 'end': 691, 'mesh': 'C032151'}, {'text': 'digitalis', 'type': 'Chemical', 'start': 696, 'end': 705, 'mesh': 'D004070'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 711, 'end': 721, 'mesh': 'D004837'}, {'text': 'arrhythmias', 'type': 'Disease', 'start': 730, 'end': 741, 'mesh': 'D001145'}, {'text': 'cibenzoline', 'type': 'Chemical', 'start': 861, 'end': 872, 'mesh': 'C032151'}, {'text': 'digitalis', 'type': 'Chemical', 'start': 888, 'end': 897, 'mesh': 'D004070'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 906, 'end': 916, 'mesh': 'D001145'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 962, 'end': 972, 'mesh': 'D004837'}, {'text': 'arrhythmias', 'type': 'Disease', 'start': 981, 'end': 992, 'mesh': 'D001145'}, {'text': 'cibenzoline', 'type': 'Chemical', 'start': 1045, 'end': 1056, 'mesh': 'C032151'}, {'text': 'digitalis', 'type': 'Chemical', 'start': 1061, 'end': 1070, 'mesh': 'D004070'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 1076, 'end': 1086, 'mesh': 'D004837'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 1095, 'end': 1105, 'mesh': 'D001145'}, {'text': 'cibenzoline', 'type': 'Chemical', 'start': 1233, 'end': 1244, 'mesh': 'C032151'}, {'text': 'Na', 'type': 'Chemical', 'start': 1332, 'end': 1334, 'mesh': 'D012964'}, {'text': 'Ca', 'type': 'Chemical', 'start': 1374, 'end': 1376, 'mesh': 'D002118'}]"
+855,19761039,Effect of Hibiscus rosa sinensis on reserpine-induced neurobehavioral and biochemical alterations in rats.,"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.","[{'text': 'Hibiscus rosa sinensis', 'type': 'Chemical', 'start': 10, 'end': 32, 'mesh': 'D010936'}, {'text': 'reserpine', 'type': 'Chemical', 'start': 36, 'end': 45, 'mesh': 'D012110'}, {'text': 'Hibiscus rosa sinensis', 'type': 'Chemical', 'start': 139, 'end': 161, 'mesh': 'D010936'}, {'text': 'reserpine', 'type': 'Chemical', 'start': 193, 'end': 202, 'mesh': 'D012110'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 221, 'end': 231, 'mesh': 'D004409'}, {'text': 'reserpine', 'type': 'Chemical', 'start': 306, 'end': 315, 'mesh': 'D012110'}, {'text': 'Reserpine', 'type': 'Chemical', 'start': 441, 'end': 450, 'mesh': 'D012110'}, {'text': 'Hibiscus rosa sinensis', 'type': 'Chemical', 'start': 566, 'end': 588, 'mesh': 'D010936'}, {'text': 'reserpine', 'type': 'Chemical', 'start': 712, 'end': 721, 'mesh': 'D012110'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 799, 'end': 809, 'mesh': 'D013481'}, {'text': 'glutathione', 'type': 'Chemical', 'start': 846, 'end': 857, 'mesh': 'D005978'}, {'text': 'Hibiscus rosa sinensis', 'type': 'Chemical', 'start': 1094, 'end': 1116, 'mesh': 'D010936'}, {'text': 'reserpine', 'type': 'Chemical', 'start': 1147, 'end': 1156, 'mesh': 'D012110'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 1175, 'end': 1185, 'mesh': 'D004409'}]"
+856,11704023,Comparison of aqueous and gellan ophthalmic timolol with placebo on the 24-hour heart rate response in patients on treatment for glaucoma.,"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.","[{'text': 'timolol', 'type': 'Chemical', 'start': 44, 'end': 51, 'mesh': 'D013999'}, {'text': 'glaucoma', 'type': 'Disease', 'start': 129, 'end': 137, 'mesh': 'D005901'}, {'text': 'glaucoma', 'type': 'Disease', 'start': 233, 'end': 241, 'mesh': 'D005901'}, {'text': 'timolol', 'type': 'Chemical', 'start': 437, 'end': 444, 'mesh': 'D013999'}, {'text': 'timolol', 'type': 'Chemical', 'start': 446, 'end': 453, 'mesh': 'D013999'}, {'text': 'timolol', 'type': 'Chemical', 'start': 475, 'end': 482, 'mesh': 'D013999'}, {'text': 'timolol', 'type': 'Chemical', 'start': 546, 'end': 553, 'mesh': 'D013999'}, {'text': 'glaucoma', 'type': 'Disease', 'start': 628, 'end': 636, 'mesh': 'D005901'}, {'text': 'open-angle glaucoma', 'type': 'Disease', 'start': 736, 'end': 755, 'mesh': 'D005902'}, {'text': 'ocular hypertension', 'type': 'Disease', 'start': 759, 'end': 778, 'mesh': 'D009798'}, {'text': 'timolol', 'type': 'Chemical', 'start': 954, 'end': 961, 'mesh': 'D013999'}, {'text': 'timolol', 'type': 'Chemical', 'start': 1010, 'end': 1017, 'mesh': 'D013999'}, {'text': 'timolol', 'type': 'Chemical', 'start': 1203, 'end': 1210, 'mesh': 'D013999'}, {'text': 'timolol', 'type': 'Chemical', 'start': 1224, 'end': 1231, 'mesh': 'D013999'}, {'text': 'Timolol', 'type': 'Chemical', 'start': 1423, 'end': 1430, 'mesh': 'D013999'}, {'text': 'timolol', 'type': 'Chemical', 'start': 1536, 'end': 1543, 'mesh': 'D013999'}, {'text': 'timolol', 'type': 'Chemical', 'start': 1615, 'end': 1622, 'mesh': 'D013999'}, {'text': 'timolol', 'type': 'Chemical', 'start': 1667, 'end': 1674, 'mesh': 'D013999'}, {'text': 'timolol', 'type': 'Chemical', 'start': 1798, 'end': 1805, 'mesh': 'D013999'}, {'text': 'timolol', 'type': 'Chemical', 'start': 1819, 'end': 1826, 'mesh': 'D013999'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 1993, 'end': 2004, 'mesh': 'D001919'}, {'text': 'glaucoma', 'type': 'Disease', 'start': 2100, 'end': 2108, 'mesh': 'D005901'}]"
+857,19300240,5 flourouracil-induced apical ballooning syndrome: a case report.,"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.","[{'text': '5 flourouracil', 'type': 'Chemical', 'start': 0, 'end': 14, 'mesh': 'D005472'}, {'text': 'apical ballooning syndrome', 'type': 'Disease', 'start': 23, 'end': 49, 'mesh': 'D054549'}, {'text': 'apical ballooning syndrome', 'type': 'Disease', 'start': 70, 'end': 96, 'mesh': 'D054549'}, {'text': 'ABS', 'type': 'Disease', 'start': 98, 'end': 101, 'mesh': 'D054549'}, {'text': 'acute cardiac syndrome', 'type': 'Disease', 'start': 143, 'end': 165, 'mesh': 'D006331'}, {'text': 'hyperkinesis', 'type': 'Disease', 'start': 260, 'end': 272, 'mesh': 'D006948'}, {'text': 'epicardial coronary disease', 'type': 'Disease', 'start': 337, 'end': 364, 'mesh': 'D003327'}, {'text': 'Cardiotoxicity', 'type': 'Disease', 'start': 366, 'end': 380, 'mesh': 'D066126'}, {'text': 'ABS', 'type': 'Disease', 'start': 476, 'end': 479, 'mesh': 'D054549'}, {'text': 'cancer', 'type': 'Disease', 'start': 611, 'end': 617, 'mesh': 'D009369'}, {'text': 'ischemic', 'type': 'Disease', 'start': 662, 'end': 670, 'mesh': 'D007511'}, {'text': 'chest pain', 'type': 'Disease', 'start': 671, 'end': 681, 'mesh': 'D002637'}, {'text': 'fluorouracil', 'type': 'Chemical', 'start': 815, 'end': 827, 'mesh': 'D005472'}, {'text': 'colorectal cancer', 'type': 'Disease', 'start': 843, 'end': 860, 'mesh': 'D015179'}, {'text': 'akinetic', 'type': 'Disease', 'start': 974, 'end': 982, 'mesh': 'D018476'}, {'text': 'akinesis', 'type': 'Disease', 'start': 1233, 'end': 1241, 'mesh': 'D018476'}, {'text': 'cardiac complications', 'type': 'Disease', 'start': 1270, 'end': 1291, 'mesh': 'D005117'}, {'text': 'cancer', 'type': 'Disease', 'start': 1295, 'end': 1301, 'mesh': 'D009369'}, {'text': 'coronary vasospasm', 'type': 'Disease', 'start': 1343, 'end': 1361, 'mesh': 'D003329'}, {'text': 'thrombus', 'type': 'Disease', 'start': 1397, 'end': 1405, 'mesh': 'D013927'}, {'text': 'catecholamines', 'type': 'Chemical', 'start': 1472, 'end': 1486, 'mesh': 'D002395'}, {'text': 'cancer', 'type': 'Disease', 'start': 1530, 'end': 1536, 'mesh': 'D009369'}, {'text': 'ABS', 'type': 'Disease', 'start': 1611, 'end': 1614, 'mesh': 'D054549'}]"
+858,18006530,Reduction of pain during induction with target-controlled propofol and remifentanil.,"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).","[{'text': 'pain', 'type': 'Disease', 'start': 13, 'end': 17, 'mesh': 'D010146'}, {'text': 'propofol', 'type': 'Chemical', 'start': 58, 'end': 66, 'mesh': 'D015742'}, {'text': 'remifentanil', 'type': 'Chemical', 'start': 71, 'end': 83, 'mesh': 'C071741'}, {'text': 'Pain', 'type': 'Disease', 'start': 97, 'end': 101, 'mesh': 'D010146'}, {'text': 'propofol', 'type': 'Chemical', 'start': 118, 'end': 126, 'mesh': 'D015742'}, {'text': 'propofol', 'type': 'Chemical', 'start': 163, 'end': 171, 'mesh': 'D015742'}, {'text': 'pain', 'type': 'Disease', 'start': 181, 'end': 185, 'mesh': 'D010146'}, {'text': 'remifentanil', 'type': 'Chemical', 'start': 217, 'end': 229, 'mesh': 'C071741'}, {'text': 'propofol', 'type': 'Chemical', 'start': 250, 'end': 258, 'mesh': 'D015742'}, {'text': 'remifentanil', 'type': 'Chemical', 'start': 486, 'end': 498, 'mesh': 'C071741'}, {'text': 'pain', 'type': 'Disease', 'start': 514, 'end': 518, 'mesh': 'D010146'}, {'text': 'remifentanil', 'type': 'Chemical', 'start': 674, 'end': 686, 'mesh': 'C071741'}, {'text': 'propofol', 'type': 'Chemical', 'start': 833, 'end': 841, 'mesh': 'D015742'}, {'text': 'Remifentanil', 'type': 'Chemical', 'start': 855, 'end': 867, 'mesh': 'C071741'}, {'text': 'remifentanil', 'type': 'Chemical', 'start': 915, 'end': 927, 'mesh': 'C071741'}, {'text': 'pain', 'type': 'Disease', 'start': 942, 'end': 946, 'mesh': 'D010146'}, {'text': 'propofol', 'type': 'Chemical', 'start': 957, 'end': 965, 'mesh': 'D015742'}, {'text': 'propofol', 'type': 'Chemical', 'start': 1016, 'end': 1024, 'mesh': 'D015742'}, {'text': 'pain', 'type': 'Disease', 'start': 1061, 'end': 1065, 'mesh': 'D010146'}, {'text': 'Pain', 'type': 'Disease', 'start': 1204, 'end': 1208, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 1330, 'end': 1334, 'mesh': 'D010146'}, {'text': 'propofol', 'type': 'Chemical', 'start': 1498, 'end': 1506, 'mesh': 'D015742'}, {'text': 'remifentanil', 'type': 'Chemical', 'start': 1511, 'end': 1523, 'mesh': 'C071741'}, {'text': 'propofol', 'type': 'Chemical', 'start': 1552, 'end': 1560, 'mesh': 'D015742'}, {'text': 'pain', 'type': 'Disease', 'start': 1570, 'end': 1574, 'mesh': 'D010146'}, {'text': 'remifentanil', 'type': 'Chemical', 'start': 1649, 'end': 1661, 'mesh': 'C071741'}]"
+859,17702969,Prenatal exposure to fluoxetine induces fetal pulmonary hypertension in the rat.,"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.","[{'text': 'fluoxetine', 'type': 'Chemical', 'start': 21, 'end': 31, 'mesh': 'D005473'}, {'text': 'Fluoxetine', 'type': 'Chemical', 'start': 92, 'end': 102, 'mesh': 'D005473'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 118, 'end': 127, 'mesh': 'D012701'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 227, 'end': 237, 'mesh': 'D005473'}, {'text': 'pulmonary hypertension syndrome', 'type': 'Disease', 'start': 297, 'end': 328, 'mesh': 'D006976'}, {'text': 'pulmonary hypertension', 'type': 'Disease', 'start': 453, 'end': 475, 'mesh': 'D006976'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 487, 'end': 497, 'mesh': 'D005473'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 551, 'end': 561, 'mesh': 'D005473'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 707, 'end': 717, 'mesh': 'D005473'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 872, 'end': 882, 'mesh': 'D005473'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 1194, 'end': 1200, 'mesh': 'D010100'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 1293, 'end': 1303, 'mesh': 'D005473'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 1340, 'end': 1350, 'mesh': 'D005473'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 1453, 'end': 1462, 'mesh': 'D012701'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 1541, 'end': 1551, 'mesh': 'D005473'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 1737, 'end': 1747, 'mesh': 'D005473'}, {'text': 'pulmonary hypertension', 'type': 'Disease', 'start': 1774, 'end': 1796, 'mesh': 'D006976'}]"
+860,17344330,Syncope and QT prolongation among patients treated with methadone for heroin dependence in the city of Copenhagen.,"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.","[{'text': 'Syncope', 'type': 'Disease', 'start': 0, 'end': 7, 'mesh': 'D013575'}, {'text': 'QT prolongation', 'type': 'Disease', 'start': 12, 'end': 27, 'mesh': 'D008133'}, {'text': 'methadone', 'type': 'Chemical', 'start': 56, 'end': 65, 'mesh': 'D008691'}, {'text': 'heroin', 'type': 'Chemical', 'start': 70, 'end': 76, 'mesh': 'D003932'}, {'text': 'Methadone', 'type': 'Chemical', 'start': 127, 'end': 136, 'mesh': 'D008691'}, {'text': 'heroin', 'type': 'Chemical', 'start': 154, 'end': 160, 'mesh': 'D003932'}, {'text': 'torsade de pointes', 'type': 'Disease', 'start': 261, 'end': 279, 'mesh': 'D016171'}, {'text': 'TdP', 'type': 'Disease', 'start': 281, 'end': 284, 'mesh': 'D016171'}, {'text': 'methadone', 'type': 'Chemical', 'start': 307, 'end': 316, 'mesh': 'D008691'}, {'text': 'heroin', 'type': 'Chemical', 'start': 327, 'end': 333, 'mesh': 'D003932'}, {'text': 'syncope', 'type': 'Disease', 'start': 430, 'end': 437, 'mesh': 'D013575'}, {'text': 'TdP', 'type': 'Disease', 'start': 501, 'end': 504, 'mesh': 'D016171'}, {'text': 'methadone', 'type': 'Chemical', 'start': 630, 'end': 639, 'mesh': 'D008691'}, {'text': 'heroin', 'type': 'Chemical', 'start': 754, 'end': 760, 'mesh': 'D003932'}, {'text': 'methadone', 'type': 'Chemical', 'start': 782, 'end': 791, 'mesh': 'D008691'}, {'text': 'buprenorphine', 'type': 'Chemical', 'start': 795, 'end': 808, 'mesh': 'D002047'}, {'text': 'syncope', 'type': 'Disease', 'start': 1051, 'end': 1058, 'mesh': 'D013575'}, {'text': 'methadone', 'type': 'Chemical', 'start': 1108, 'end': 1117, 'mesh': 'D008691'}, {'text': 'syncope', 'type': 'Disease', 'start': 1140, 'end': 1147, 'mesh': 'D013575'}, {'text': 'Methadone', 'type': 'Chemical', 'start': 1246, 'end': 1255, 'mesh': 'D008691'}, {'text': 'buprenorphine', 'type': 'Chemical', 'start': 1351, 'end': 1364, 'mesh': 'D002047'}, {'text': 'methadone', 'type': 'Chemical', 'start': 1416, 'end': 1425, 'mesh': 'D008691'}, {'text': 'prolonged QTc interval', 'type': 'Disease', 'start': 1453, 'end': 1475, 'mesh': 'D008133'}, {'text': 'buprenorphine', 'type': 'Chemical', 'start': 1511, 'end': 1524, 'mesh': 'D002047'}, {'text': 'methadone', 'type': 'Chemical', 'start': 1574, 'end': 1583, 'mesh': 'D008691'}, {'text': 'syncope', 'type': 'Disease', 'start': 1657, 'end': 1664, 'mesh': 'D013575'}, {'text': 'Methadone', 'type': 'Chemical', 'start': 1679, 'end': 1688, 'mesh': 'D008691'}, {'text': 'QT prolongation', 'type': 'Disease', 'start': 1708, 'end': 1723, 'mesh': 'D008133'}, {'text': 'syncope', 'type': 'Disease', 'start': 1748, 'end': 1755, 'mesh': 'D013575'}, {'text': 'heroin', 'type': 'Chemical', 'start': 1775, 'end': 1781, 'mesh': 'D003932'}]"
+861,16826348,Peripheral neuropathy caused by high-dose cytosine arabinoside treatment in a patient with acute myeloid leukemia.,"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.","[{'text': 'Peripheral neuropathy', 'type': 'Disease', 'start': 0, 'end': 21, 'mesh': 'D010523'}, {'text': 'cytosine arabinoside', 'type': 'Chemical', 'start': 42, 'end': 62, 'mesh': 'D003561'}, {'text': 'acute myeloid leukemia', 'type': 'Disease', 'start': 91, 'end': 113, 'mesh': 'D015470'}, {'text': 'toxicity', 'type': 'Disease', 'start': 142, 'end': 150, 'mesh': 'D064420'}, {'text': 'cytosine arabinoside', 'type': 'Chemical', 'start': 164, 'end': 184, 'mesh': 'D003561'}, {'text': 'toxicity', 'type': 'Disease', 'start': 213, 'end': 221, 'mesh': 'D064420'}, {'text': 'cytosine arabinoside', 'type': 'Chemical', 'start': 225, 'end': 245, 'mesh': 'D003561'}, {'text': 'acute myeloid leukemia', 'type': 'Disease', 'start': 357, 'end': 379, 'mesh': 'D015470'}, {'text': 'cytosine arabinoside', 'type': 'Chemical', 'start': 441, 'end': 461, 'mesh': 'D003561'}, {'text': 'cytosine arabinoside', 'type': 'Chemical', 'start': 576, 'end': 596, 'mesh': 'D003561'}, {'text': 'numbness', 'type': 'Disease', 'start': 705, 'end': 713, 'mesh': 'D006987'}, {'text': 'peripheral neuropathy', 'type': 'Disease', 'start': 784, 'end': 805, 'mesh': 'D010523'}, {'text': 'neuropathy', 'type': 'Disease', 'start': 836, 'end': 846, 'mesh': 'D009422'}, {'text': 'graft-versus-host disease', 'type': 'Disease', 'start': 995, 'end': 1020, 'mesh': 'D006086'}, {'text': 'methylprednisolone', 'type': 'Chemical', 'start': 1065, 'end': 1083, 'mesh': 'D008775'}, {'text': 'peripheral neuropathy', 'type': 'Disease', 'start': 1112, 'end': 1133, 'mesh': 'D010523'}, {'text': 'cytosine arabinoside', 'type': 'Chemical', 'start': 1163, 'end': 1183, 'mesh': 'D003561'}]"
+862,16820346,Atorvastatin prevented and reversed dexamethasone-induced hypertension in the rat.,"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.","[{'text': 'Atorvastatin', 'type': 'Chemical', 'start': 0, 'end': 12, 'mesh': 'C065179'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 36, 'end': 49, 'mesh': 'D003907'}, {'text': 'hypertension', 'type': 'Disease', 'start': 58, 'end': 70, 'mesh': 'D006973'}, {'text': 'atorvastatin', 'type': 'Chemical', 'start': 120, 'end': 132, 'mesh': 'C065179'}, {'text': 'atorva', 'type': 'Chemical', 'start': 134, 'end': 140, 'mesh': 'C065179'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 145, 'end': 158, 'mesh': 'D003907'}, {'text': 'dex', 'type': 'Chemical', 'start': 160, 'end': 163, 'mesh': 'D003907'}, {'text': 'hypertension', 'type': 'Disease', 'start': 173, 'end': 185, 'mesh': 'D006973'}, {'text': 'atorva', 'type': 'Chemical', 'start': 233, 'end': 239, 'mesh': 'C065179'}, {'text': 'Dex', 'type': 'Chemical', 'start': 279, 'end': 282, 'mesh': 'D003907'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 371, 'end': 381, 'mesh': 'D013481'}, {'text': 'dex', 'type': 'Chemical', 'start': 426, 'end': 429, 'mesh': 'D003907'}, {'text': 'atorva', 'type': 'Chemical', 'start': 480, 'end': 486, 'mesh': 'C065179'}, {'text': 'dex', 'type': 'Chemical', 'start': 489, 'end': 492, 'mesh': 'D003907'}, {'text': 'dex', 'type': 'Chemical', 'start': 596, 'end': 599, 'mesh': 'D003907'}, {'text': 'Atorva', 'type': 'Chemical', 'start': 624, 'end': 630, 'mesh': 'C065179'}, {'text': 'dex', 'type': 'Chemical', 'start': 640, 'end': 643, 'mesh': 'D003907'}, {'text': 'hypertension', 'type': 'Disease', 'start': 652, 'end': 664, 'mesh': 'D006973'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 737, 'end': 747, 'mesh': 'D013481'}, {'text': 'dex', 'type': 'Chemical', 'start': 764, 'end': 767, 'mesh': 'D003907'}, {'text': 'atorva', 'type': 'Chemical', 'start': 784, 'end': 790, 'mesh': 'C065179'}, {'text': 'dex', 'type': 'Chemical', 'start': 793, 'end': 796, 'mesh': 'D003907'}, {'text': 'nitrate', 'type': 'Chemical', 'start': 818, 'end': 825, 'mesh': 'D009566'}, {'text': 'nitrite', 'type': 'Chemical', 'start': 826, 'end': 833, 'mesh': 'D009573'}, {'text': 'dex', 'type': 'Chemical', 'start': 857, 'end': 860, 'mesh': 'D003907'}, {'text': 'Atorva', 'type': 'Chemical', 'start': 976, 'end': 982, 'mesh': 'C065179'}, {'text': 'atorvastatin', 'type': 'Chemical', 'start': 1036, 'end': 1048, 'mesh': 'C065179'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 1072, 'end': 1085, 'mesh': 'D003907'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1094, 'end': 1106, 'mesh': 'D006973'}]"
+863,15974569,Two prodrugs of potent and selective GluR5 kainate receptor antagonists actives in three animal models of pain.,"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.","[{'text': 'kainate', 'type': 'Chemical', 'start': 43, 'end': 50, 'mesh': 'D007608'}, {'text': 'pain', 'type': 'Disease', 'start': 106, 'end': 110, 'mesh': 'D010146'}, {'text': 'KA', 'type': 'Chemical', 'start': 176, 'end': 178, 'mesh': 'D007608'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 251, 'end': 260, 'mesh': 'D018698'}, {'text': 'pain', 'type': 'Disease', 'start': 339, 'end': 343, 'mesh': 'D010146'}, {'text': 'formalin', 'type': 'Chemical', 'start': 357, 'end': 365, 'mesh': 'D005557'}, {'text': 'carrageenan', 'type': 'Chemical', 'start': 387, 'end': 398, 'mesh': 'D002351'}, {'text': 'thermal hyperalgesia', 'type': 'Disease', 'start': 407, 'end': 427, 'mesh': 'D006930'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 433, 'end': 442, 'mesh': 'D002211'}, {'text': 'mechanical hyperalgesia', 'type': 'Disease', 'start': 451, 'end': 474, 'mesh': 'D006930'}]"
+864,11583940,Sirolimus and mycophenolate mofetil for calcineurin-free immunosuppression in renal transplant recipients.,"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.","[{'text': 'Sirolimus', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D020123'}, {'text': 'mycophenolate mofetil', 'type': 'Chemical', 'start': 14, 'end': 35, 'mesh': 'C063008'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 139, 'end': 151, 'mesh': 'D016572'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 156, 'end': 166, 'mesh': 'D016559'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 354, 'end': 368, 'mesh': 'D007674'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 376, 'end': 390, 'mesh': 'D007674'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 496, 'end': 510, 'mesh': 'D007674'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 566, 'end': 580, 'mesh': 'D007674'}, {'text': 'mycophenolate mofetil', 'type': 'Chemical', 'start': 716, 'end': 737, 'mesh': 'C063008'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 742, 'end': 751, 'mesh': 'D020123'}, {'text': 'rapamycin', 'type': 'Chemical', 'start': 753, 'end': 762, 'mesh': 'D020123'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 773, 'end': 787, 'mesh': 'D007674'}]"
+865,11245434,Erythropoietin restores the anemia-induced reduction in cyclophosphamide cytotoxicity in rat tumors.,"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.","[{'text': 'anemia', 'type': 'Disease', 'start': 28, 'end': 34, 'mesh': 'D000740'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 56, 'end': 72, 'mesh': 'D003520'}, {'text': 'cytotoxicity', 'type': 'Disease', 'start': 73, 'end': 85, 'mesh': 'D064420'}, {'text': 'tumors', 'type': 'Disease', 'start': 93, 'end': 99, 'mesh': 'D009369'}, {'text': 'anemia', 'type': 'Disease', 'start': 152, 'end': 158, 'mesh': 'D000740'}, {'text': 'cytotoxicity', 'type': 'Disease', 'start': 232, 'end': 244, 'mesh': 'D064420'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 248, 'end': 264, 'mesh': 'D003520'}, {'text': 'tumors', 'type': 'Disease', 'start': 287, 'end': 293, 'mesh': 'D009369'}, {'text': 'Anemia', 'type': 'Disease', 'start': 295, 'end': 301, 'mesh': 'D000740'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 337, 'end': 348, 'mesh': 'D016190'}, {'text': 'anemia', 'type': 'Disease', 'start': 480, 'end': 486, 'mesh': 'D000740'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 582, 'end': 593, 'mesh': 'D016190'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 623, 'end': 634, 'mesh': 'D016190'}, {'text': 'tumors', 'type': 'Disease', 'start': 646, 'end': 652, 'mesh': 'D009369'}, {'text': 'sarcoma', 'type': 'Disease', 'start': 657, 'end': 664, 'mesh': 'D012509'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 732, 'end': 743, 'mesh': 'D016190'}, {'text': 'tumor', 'type': 'Disease', 'start': 776, 'end': 781, 'mesh': 'D009369'}, {'text': 'tumors', 'type': 'Disease', 'start': 807, 'end': 813, 'mesh': 'D009369'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 849, 'end': 865, 'mesh': 'D003520'}, {'text': 'tumors', 'type': 'Disease', 'start': 958, 'end': 964, 'mesh': 'D009369'}, {'text': 'anemia', 'type': 'Disease', 'start': 986, 'end': 992, 'mesh': 'D000740'}, {'text': 'anemia', 'type': 'Disease', 'start': 1124, 'end': 1130, 'mesh': 'D000740'}, {'text': 'anemia', 'type': 'Disease', 'start': 1287, 'end': 1293, 'mesh': 'D000740'}, {'text': 'cytotoxicity', 'type': 'Disease', 'start': 1302, 'end': 1314, 'mesh': 'D064420'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 1318, 'end': 1334, 'mesh': 'D003520'}, {'text': 'tumors', 'type': 'Disease', 'start': 1338, 'end': 1344, 'mesh': 'D009369'}, {'text': 'anemia', 'type': 'Disease', 'start': 1368, 'end': 1374, 'mesh': 'D000740'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 1474, 'end': 1480, 'mesh': 'D010100'}, {'text': 'tumor', 'type': 'Disease', 'start': 1491, 'end': 1496, 'mesh': 'D009369'}]"
+866,11243580,The role of nitrergic system in lidocaine-induced convulsion in the mouse.,"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.","[{'text': 'lidocaine', 'type': 'Chemical', 'start': 32, 'end': 41, 'mesh': 'D008012'}, {'text': 'convulsion', 'type': 'Disease', 'start': 50, 'end': 60, 'mesh': 'D012640'}, {'text': 'N-nitro-L-arginine-methyl ester', 'type': 'Chemical', 'start': 90, 'end': 121, 'mesh': 'D019331'}, {'text': 'L-NAME', 'type': 'Chemical', 'start': 123, 'end': 129, 'mesh': 'D019331'}, {'text': 'nitric oxide', 'type': 'Chemical', 'start': 133, 'end': 145, 'mesh': 'D009569'}, {'text': 'NO', 'type': 'Chemical', 'start': 147, 'end': 149, 'mesh': 'D009569'}, {'text': 'L-arginine', 'type': 'Chemical', 'start': 174, 'end': 184, 'mesh': 'D001120'}, {'text': 'NO', 'type': 'Chemical', 'start': 188, 'end': 190, 'mesh': 'D009569'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 223, 'end': 232, 'mesh': 'D008012'}, {'text': 'convulsions', 'type': 'Disease', 'start': 241, 'end': 252, 'mesh': 'D012640'}, {'text': 'L-arginine', 'type': 'Chemical', 'start': 337, 'end': 347, 'mesh': 'D001120'}, {'text': 'L-NAME', 'type': 'Chemical', 'start': 367, 'end': 373, 'mesh': 'D019331'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 396, 'end': 404, 'mesh': 'D003975'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 487, 'end': 496, 'mesh': 'D008012'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 683, 'end': 692, 'mesh': 'D008012'}, {'text': 'L-NAME', 'type': 'Chemical', 'start': 705, 'end': 711, 'mesh': 'D019331'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 734, 'end': 742, 'mesh': 'D003975'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 794, 'end': 803, 'mesh': 'D008012'}, {'text': 'convulsions', 'type': 'Disease', 'start': 823, 'end': 834, 'mesh': 'D012640'}, {'text': 'L-arginine', 'type': 'Chemical', 'start': 853, 'end': 863, 'mesh': 'D001120'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 901, 'end': 910, 'mesh': 'D008012'}, {'text': 'convulsions', 'type': 'Disease', 'start': 936, 'end': 947, 'mesh': 'D012640'}, {'text': 'NO', 'type': 'Chemical', 'start': 994, 'end': 996, 'mesh': 'D009569'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 1028, 'end': 1037, 'mesh': 'D008012'}, {'text': 'convulsions', 'type': 'Disease', 'start': 1046, 'end': 1057, 'mesh': 'D012640'}]"
+867,11079278,Effect of intravenous metoprolol or intravenous metoprolol plus glucagon on dobutamine-induced myocardial ischemia.,"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.","[{'text': 'metoprolol', 'type': 'Chemical', 'start': 22, 'end': 32, 'mesh': 'D008790'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 48, 'end': 58, 'mesh': 'D008790'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 76, 'end': 86, 'mesh': 'D004280'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 95, 'end': 114, 'mesh': 'D017202'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 160, 'end': 170, 'mesh': 'D008790'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 174, 'end': 184, 'mesh': 'D004280'}, {'text': 'technetium-99m sestamibi', 'type': 'Chemical', 'start': 205, 'end': 229, 'mesh': 'D017256'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 360, 'end': 370, 'mesh': 'D008790'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 575, 'end': 585, 'mesh': 'D004280'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 629, 'end': 639, 'mesh': 'D004280'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 757, 'end': 767, 'mesh': 'D008790'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 771, 'end': 781, 'mesh': 'D008790'}, {'text': 'Metoprolol', 'type': 'Chemical', 'start': 802, 'end': 812, 'mesh': 'D008790'}, {'text': 'predobutamine', 'type': 'Chemical', 'start': 844, 'end': 857, 'mesh': '-1'}, {'text': 'Metoprolol', 'type': 'Chemical', 'start': 960, 'end': 970, 'mesh': 'D008790'}, {'text': 'Metoprolol', 'type': 'Chemical', 'start': 1078, 'end': 1088, 'mesh': 'D008790'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 1363, 'end': 1373, 'mesh': 'D008790'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 1378, 'end': 1388, 'mesh': 'D008790'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 1418, 'end': 1428, 'mesh': 'D004280'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 1445, 'end': 1455, 'mesh': 'D008790'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 1493, 'end': 1512, 'mesh': 'D017202'}]"
+868,10910842,Prednisolone-induced muscle dysfunction is caused more by atrophy than by altered acetylcholine receptor expression.,"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.","[{'text': 'Prednisolone', 'type': 'Chemical', 'start': 0, 'end': 12, 'mesh': 'D011239'}, {'text': 'muscle dysfunction', 'type': 'Disease', 'start': 21, 'end': 39, 'mesh': 'D018908'}, {'text': 'atrophy', 'type': 'Disease', 'start': 58, 'end': 65, 'mesh': 'D001284'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 82, 'end': 95, 'mesh': 'D000109'}, {'text': 'prednisolone', 'type': 'Chemical', 'start': 324, 'end': 336, 'mesh': 'D011239'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 427, 'end': 440, 'mesh': 'D000109'}, {'text': 'prednisolone', 'type': 'Chemical', 'start': 593, 'end': 605, 'mesh': 'D011239'}, {'text': 'prednisolone', 'type': 'Chemical', 'start': 629, 'end': 641, 'mesh': 'D011239'}, {'text': 'tetanic', 'type': 'Disease', 'start': 852, 'end': 859, 'mesh': 'D013746'}, {'text': 'd-tubocurarine', 'type': 'Chemical', 'start': 920, 'end': 934, 'mesh': 'D014403'}, {'text': 'tetanic', 'type': 'Disease', 'start': 1246, 'end': 1253, 'mesh': 'D013746'}, {'text': 'd-tubocurarine', 'type': 'Chemical', 'start': 1443, 'end': 1457, 'mesh': 'D014403'}, {'text': 'd-tubocurarine', 'type': 'Chemical', 'start': 1796, 'end': 1810, 'mesh': 'D014403'}, {'text': 'neuromuscular dysfunction', 'type': 'Disease', 'start': 1895, 'end': 1920, 'mesh': 'D009468'}, {'text': 'prednisolone', 'type': 'Chemical', 'start': 1927, 'end': 1939, 'mesh': 'D011239'}, {'text': 'muscle atrophy', 'type': 'Disease', 'start': 1986, 'end': 2000, 'mesh': 'D009133'}, {'text': 'muscle atrophy', 'type': 'Disease', 'start': 2267, 'end': 2281, 'mesh': 'D009133'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 2314, 'end': 2327, 'mesh': 'D000109'}]"
+869,10533019,Rapid reversal of life-threatening diltiazem-induced tetany with calcium chloride.,"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.","[{'text': 'diltiazem', 'type': 'Chemical', 'start': 35, 'end': 44, 'mesh': 'D004110'}, {'text': 'tetany', 'type': 'Disease', 'start': 53, 'end': 59, 'mesh': 'D013746'}, {'text': 'calcium chloride', 'type': 'Chemical', 'start': 65, 'end': 81, 'mesh': 'D002122'}, {'text': 'tetany', 'type': 'Disease', 'start': 119, 'end': 125, 'mesh': 'D013746'}, {'text': 'respiratory arrest', 'type': 'Disease', 'start': 138, 'end': 156, 'mesh': 'D012131'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 191, 'end': 200, 'mesh': 'D004110'}, {'text': 'calcium chloride', 'type': 'Chemical', 'start': 224, 'end': 240, 'mesh': 'D002122'}, {'text': 'tetany', 'type': 'Disease', 'start': 272, 'end': 278, 'mesh': 'D013746'}, {'text': 'tetany', 'type': 'Disease', 'start': 468, 'end': 474, 'mesh': 'D013746'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 523, 'end': 532, 'mesh': 'D004110'}, {'text': 'calcium chloride', 'type': 'Chemical', 'start': 542, 'end': 558, 'mesh': 'D002122'}]"
+870,10414674,Effects of nonsteroidal anti-inflammatory drugs on hemostasis in patients with aneurysmal subarachnoid hemorrhage.,"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.","[{'text': 'aneurysmal subarachnoid hemorrhage', 'type': 'Disease', 'start': 79, 'end': 113, 'mesh': 'D013345'}, {'text': 'aneurysmal subarachnoid hemorrhage', 'type': 'Disease', 'start': 327, 'end': 361, 'mesh': 'D013345'}, {'text': 'SAH', 'type': 'Disease', 'start': 363, 'end': 366, 'mesh': 'D013345'}, {'text': 'ketoprofen', 'type': 'Chemical', 'start': 402, 'end': 412, 'mesh': 'D007660'}, {'text': 'ketoprofen', 'type': 'Chemical', 'start': 441, 'end': 451, 'mesh': 'D007660'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 483, 'end': 496, 'mesh': 'D000082'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 522, 'end': 535, 'mesh': 'D000082'}, {'text': 'aneurysmal', 'type': 'Disease', 'start': 594, 'end': 604, 'mesh': 'D017542'}, {'text': 'SAH', 'type': 'Disease', 'start': 605, 'end': 608, 'mesh': 'D013345'}, {'text': 'platelet aggregation', 'type': 'Disease', 'start': 795, 'end': 815, 'mesh': 'D001791'}, {'text': 'adenosine diphosphate', 'type': 'Chemical', 'start': 839, 'end': 860, 'mesh': 'D000244'}, {'text': 'ketoprofen', 'type': 'Chemical', 'start': 895, 'end': 905, 'mesh': 'D007660'}, {'text': 'ketoprofen', 'type': 'Chemical', 'start': 946, 'end': 956, 'mesh': 'D007660'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 975, 'end': 988, 'mesh': 'D000082'}, {'text': 'platelet aggregation', 'type': 'Disease', 'start': 1072, 'end': 1092, 'mesh': 'D001791'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 1110, 'end': 1123, 'mesh': 'D000082'}, {'text': 'platelet aggregation', 'type': 'Disease', 'start': 1195, 'end': 1215, 'mesh': 'D001791'}, {'text': 'ketoprofen', 'type': 'Chemical', 'start': 1254, 'end': 1264, 'mesh': 'D007660'}, {'text': 'hematoma', 'type': 'Disease', 'start': 1310, 'end': 1318, 'mesh': 'D006406'}, {'text': 'Ketoprofen', 'type': 'Chemical', 'start': 1498, 'end': 1508, 'mesh': 'D007660'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 1517, 'end': 1530, 'mesh': 'D000082'}, {'text': 'SAH', 'type': 'Disease', 'start': 1575, 'end': 1578, 'mesh': 'D013345'}, {'text': 'ketoprofen', 'type': 'Chemical', 'start': 1583, 'end': 1593, 'mesh': 'D007660'}, {'text': 'artery aneurysms', 'type': 'Disease', 'start': 1629, 'end': 1645, 'mesh': 'D002532'}, {'text': 'hemorrhage', 'type': 'Disease', 'start': 1689, 'end': 1699, 'mesh': 'D006470'}]"
+871,9523850,Value of methylprednisolone in prevention of the arthralgia-myalgia syndrome associated with the total dose infusion of iron dextran: a double blind randomized trial.,"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.","[{'text': 'methylprednisolone', 'type': 'Chemical', 'start': 9, 'end': 27, 'mesh': 'D008775'}, {'text': 'arthralgia', 'type': 'Disease', 'start': 49, 'end': 59, 'mesh': 'D018771'}, {'text': 'myalgia', 'type': 'Disease', 'start': 60, 'end': 67, 'mesh': 'D063806'}, {'text': 'iron dextran', 'type': 'Chemical', 'start': 120, 'end': 132, 'mesh': 'D007505'}, {'text': 'iron dextran', 'type': 'Chemical', 'start': 223, 'end': 235, 'mesh': 'D007505'}, {'text': 'arthralgia', 'type': 'Disease', 'start': 293, 'end': 303, 'mesh': 'D018771'}, {'text': 'myalgia', 'type': 'Disease', 'start': 304, 'end': 311, 'mesh': 'D063806'}, {'text': 'methylprednisolone', 'type': 'Chemical', 'start': 459, 'end': 477, 'mesh': 'D008775'}, {'text': 'MP', 'type': 'Chemical', 'start': 479, 'end': 481, 'mesh': 'D008775'}, {'text': 'MP', 'type': 'Chemical', 'start': 648, 'end': 650, 'mesh': 'D008775'}, {'text': 'MP', 'type': 'Chemical', 'start': 705, 'end': 707, 'mesh': 'D008775'}, {'text': 'MP', 'type': 'Chemical', 'start': 1254, 'end': 1256, 'mesh': 'D008775'}, {'text': 'arthralgia', 'type': 'Disease', 'start': 1320, 'end': 1330, 'mesh': 'D018771'}, {'text': 'myalgia', 'type': 'Disease', 'start': 1331, 'end': 1338, 'mesh': 'D063806'}, {'text': 'MP', 'type': 'Chemical', 'start': 1378, 'end': 1380, 'mesh': 'D008775'}, {'text': 'iron dextran', 'type': 'Chemical', 'start': 1431, 'end': 1443, 'mesh': 'D007505'}]"
+872,8384253,Long-term effects of vincristine on the peripheral nervous system.,"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.","[{'text': 'vincristine', 'type': 'Chemical', 'start': 21, 'end': 32, 'mesh': 'D014750'}, {'text': ""Non-Hodgkin's Lymphoma"", 'type': 'Disease', 'start': 87, 'end': 109, 'mesh': 'D008228'}, {'text': 'vincristine', 'type': 'Chemical', 'start': 123, 'end': 134, 'mesh': 'D014750'}, {'text': 'vincristine', 'type': 'Chemical', 'start': 260, 'end': 271, 'mesh': 'D014750'}, {'text': 'neuropathic symptoms', 'type': 'Disease', 'start': 353, 'end': 373, 'mesh': 'D012678'}, {'text': 'vincristine', 'type': 'Chemical', 'start': 561, 'end': 572, 'mesh': 'D014750'}, {'text': 'neuropathic symptoms', 'type': 'Disease', 'start': 615, 'end': 635, 'mesh': 'D012678'}, {'text': 'vincristine', 'type': 'Chemical', 'start': 1177, 'end': 1188, 'mesh': 'D014750'}, {'text': 'vincristine', 'type': 'Chemical', 'start': 1225, 'end': 1236, 'mesh': 'D014750'}, {'text': 'neuropathy', 'type': 'Disease', 'start': 1237, 'end': 1247, 'mesh': 'D009422'}]"
+873,8268147,A case of polymyositis in a patient with primary biliary cirrhosis treated with D-penicillamine.,"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.","[{'text': 'polymyositis', 'type': 'Disease', 'start': 10, 'end': 22, 'mesh': 'D017285'}, {'text': 'primary biliary cirrhosis', 'type': 'Disease', 'start': 41, 'end': 66, 'mesh': 'D008105'}, {'text': 'D-penicillamine', 'type': 'Chemical', 'start': 80, 'end': 95, 'mesh': 'D010396'}, {'text': 'D-penicillamine', 'type': 'Chemical', 'start': 106, 'end': 121, 'mesh': 'D010396'}, {'text': 'rheumatologic diseases', 'type': 'Disease', 'start': 145, 'end': 167, 'mesh': 'D012216'}, {'text': 'toxicity', 'type': 'Disease', 'start': 169, 'end': 177, 'mesh': 'D064420'}, {'text': 'Polymyositis', 'type': 'Disease', 'start': 218, 'end': 230, 'mesh': 'D017285'}, {'text': 'dermatomyositis', 'type': 'Disease', 'start': 231, 'end': 246, 'mesh': 'D003882'}, {'text': 'D-penicillamine', 'type': 'Chemical', 'start': 301, 'end': 316, 'mesh': 'D010396'}, {'text': 'primary biliary cirrhosis', 'type': 'Disease', 'start': 397, 'end': 422, 'mesh': 'D008105'}, {'text': 'polymyositis', 'type': 'Disease', 'start': 438, 'end': 450, 'mesh': 'D017285'}, {'text': 'D-penicillamine', 'type': 'Chemical', 'start': 467, 'end': 482, 'mesh': 'D010396'}, {'text': 'D-penicillamine', 'type': 'Chemical', 'start': 568, 'end': 583, 'mesh': 'D010396'}, {'text': 'polymyositis', 'type': 'Disease', 'start': 674, 'end': 686, 'mesh': 'D017285'}, {'text': 'dermatomyositis', 'type': 'Disease', 'start': 687, 'end': 702, 'mesh': 'D003882'}]"
+874,8251368,Photodistributed nifedipine-induced facial telangiectasia.,"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.","[{'text': 'nifedipine', 'type': 'Chemical', 'start': 17, 'end': 27, 'mesh': 'D009543'}, {'text': 'telangiectasia', 'type': 'Disease', 'start': 43, 'end': 57, 'mesh': 'D013684'}, {'text': 'nifedipine', 'type': 'Chemical', 'start': 86, 'end': 96, 'mesh': 'D009543'}, {'text': 'Adalat', 'type': 'Chemical', 'start': 98, 'end': 104, 'mesh': 'D009543'}, {'text': 'telangiectasia', 'type': 'Disease', 'start': 154, 'end': 168, 'mesh': 'D013684'}, {'text': 'flushing', 'type': 'Disease', 'start': 260, 'end': 268, 'mesh': 'D005483'}, {'text': 'amlodipine', 'type': 'Chemical', 'start': 397, 'end': 407, 'mesh': 'D017311'}, {'text': 'telangiectasia', 'type': 'Disease', 'start': 442, 'end': 456, 'mesh': 'D013684'}, {'text': 'telangiectasia', 'type': 'Disease', 'start': 487, 'end': 501, 'mesh': 'D013684'}]"
+875,7542793,Nephrotoxicity of cyclosporin A and FK506: inhibition of calcineurin phosphatase.,"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.","[{'text': 'Nephrotoxicity', 'type': 'Disease', 'start': 0, 'end': 14, 'mesh': 'D007674'}, {'text': 'cyclosporin A', 'type': 'Chemical', 'start': 18, 'end': 31, 'mesh': 'D016572'}, {'text': 'FK506', 'type': 'Chemical', 'start': 36, 'end': 41, 'mesh': 'D016559'}, {'text': 'Cyclosporin A', 'type': 'Chemical', 'start': 82, 'end': 95, 'mesh': 'D016572'}, {'text': 'CsA', 'type': 'Chemical', 'start': 97, 'end': 100, 'mesh': 'D016572'}, {'text': 'Fujimycine', 'type': 'Chemical', 'start': 116, 'end': 126, 'mesh': 'D016559'}, {'text': 'FK506', 'type': 'Chemical', 'start': 128, 'end': 133, 'mesh': 'D016559'}, {'text': 'macrolide', 'type': 'Chemical', 'start': 165, 'end': 174, 'mesh': 'D018942'}, {'text': 'rapamycin', 'type': 'Chemical', 'start': 193, 'end': 202, 'mesh': 'D020123'}, {'text': 'hypertrophy', 'type': 'Disease', 'start': 321, 'end': 332, 'mesh': 'D006984'}, {'text': 'CsA', 'type': 'Chemical', 'start': 438, 'end': 441, 'mesh': 'D016572'}, {'text': 'FK506', 'type': 'Chemical', 'start': 446, 'end': 451, 'mesh': 'D016559'}, {'text': 'toxicity', 'type': 'Disease', 'start': 452, 'end': 460, 'mesh': 'D064420'}, {'text': 'FK506', 'type': 'Chemical', 'start': 498, 'end': 503, 'mesh': 'D016559'}, {'text': 'CsA', 'type': 'Chemical', 'start': 561, 'end': 564, 'mesh': 'D016572'}, {'text': 'FK506', 'type': 'Chemical', 'start': 569, 'end': 574, 'mesh': 'D016559'}, {'text': 'CsA', 'type': 'Chemical', 'start': 774, 'end': 777, 'mesh': 'D016572'}, {'text': 'FK506', 'type': 'Chemical', 'start': 782, 'end': 787, 'mesh': 'D016559'}, {'text': 'rapamycin', 'type': 'Chemical', 'start': 800, 'end': 809, 'mesh': 'D020123'}, {'text': 'CsA', 'type': 'Chemical', 'start': 900, 'end': 903, 'mesh': 'D016572'}, {'text': 'FK506', 'type': 'Chemical', 'start': 908, 'end': 913, 'mesh': 'D016559'}, {'text': 'rapamycin', 'type': 'Chemical', 'start': 923, 'end': 932, 'mesh': 'D020123'}, {'text': 'nephrotoxic', 'type': 'Disease', 'start': 965, 'end': 976, 'mesh': 'D007674'}, {'text': 'CsA', 'type': 'Chemical', 'start': 988, 'end': 991, 'mesh': 'D016572'}, {'text': 'FK506', 'type': 'Chemical', 'start': 996, 'end': 1001, 'mesh': 'D016559'}]"
+876,7337133,Massive cerebral edema associated with fulminant hepatic failure in acetaminophen overdose: possible role of cranial decompression.,"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.","[{'text': 'cerebral edema', 'type': 'Disease', 'start': 8, 'end': 22, 'mesh': 'D001929'}, {'text': 'hepatic failure', 'type': 'Disease', 'start': 49, 'end': 64, 'mesh': 'D017093'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 68, 'end': 81, 'mesh': 'D000082'}, {'text': 'overdose', 'type': 'Disease', 'start': 82, 'end': 90, 'mesh': 'D062787'}, {'text': 'Cerebral edema', 'type': 'Disease', 'start': 132, 'end': 146, 'mesh': 'D001929'}, {'text': 'fulminant hepatic failure', 'type': 'Disease', 'start': 176, 'end': 201, 'mesh': 'D017093'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 292, 'end': 305, 'mesh': 'D000082'}, {'text': 'fulminant hepatic failure', 'type': 'Disease', 'start': 314, 'end': 339, 'mesh': 'D017093'}, {'text': 'cerebral edema', 'type': 'Disease', 'start': 368, 'end': 382, 'mesh': 'D001929'}]"
+877,4069770,Gentamicin nephropathy in a neonate.,"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.","[{'text': 'Gentamicin', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D005839'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 11, 'end': 22, 'mesh': 'D007674'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 103, 'end': 122, 'mesh': 'D058186'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 142, 'end': 152, 'mesh': 'D005839'}, {'text': 'penicillin', 'type': 'Chemical', 'start': 171, 'end': 181, 'mesh': 'D010406'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 207, 'end': 217, 'mesh': 'D005839'}, {'text': 'anuria', 'type': 'Disease', 'start': 262, 'end': 268, 'mesh': 'D001002'}, {'text': 'periodic acid', 'type': 'Chemical', 'start': 289, 'end': 302, 'mesh': 'D010504'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 543, 'end': 553, 'mesh': 'D005839'}]"
+878,3780814,Anti-carcinogenic action of phenobarbital given simultaneously with diethylnitrosamine in the rat.,"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.","[{'text': 'carcinogenic', 'type': 'Disease', 'start': 5, 'end': 17, 'mesh': 'D063646'}, {'text': 'phenobarbital', 'type': 'Chemical', 'start': 28, 'end': 41, 'mesh': 'D010634'}, {'text': 'diethylnitrosamine', 'type': 'Chemical', 'start': 68, 'end': 86, 'mesh': 'D004052'}, {'text': 'phenobarbital', 'type': 'Chemical', 'start': 169, 'end': 182, 'mesh': 'D010634'}, {'text': 'PB', 'type': 'Chemical', 'start': 184, 'end': 186, 'mesh': 'D010634'}, {'text': 'carcinogenesis', 'type': 'Disease', 'start': 223, 'end': 237, 'mesh': 'D063646'}, {'text': 'diethylnitrosamine', 'type': 'Chemical', 'start': 282, 'end': 300, 'mesh': 'D004052'}, {'text': 'DEN', 'type': 'Chemical', 'start': 302, 'end': 305, 'mesh': 'D004052'}, {'text': 'DEN', 'type': 'Chemical', 'start': 358, 'end': 361, 'mesh': 'D004052'}, {'text': 'DEN', 'type': 'Chemical', 'start': 374, 'end': 377, 'mesh': 'D004052'}, {'text': 'PB', 'type': 'Chemical', 'start': 380, 'end': 382, 'mesh': 'D010634'}, {'text': 'hepatocarcinogenesis', 'type': 'Disease', 'start': 437, 'end': 457, 'mesh': 'D063646'}, {'text': 'preneoplastic foci', 'type': 'Disease', 'start': 539, 'end': 557, 'mesh': 'D011230'}, {'text': 'PB', 'type': 'Chemical', 'start': 589, 'end': 591, 'mesh': 'D010634'}, {'text': 'DEN', 'type': 'Chemical', 'start': 622, 'end': 625, 'mesh': 'D004052'}, {'text': 'DEN', 'type': 'Chemical', 'start': 749, 'end': 752, 'mesh': 'D004052'}, {'text': 'DEN', 'type': 'Chemical', 'start': 803, 'end': 806, 'mesh': 'D004052'}, {'text': 'PB', 'type': 'Chemical', 'start': 809, 'end': 811, 'mesh': 'D010634'}, {'text': 'PB', 'type': 'Chemical', 'start': 880, 'end': 882, 'mesh': 'D010634'}, {'text': 'DEN', 'type': 'Chemical', 'start': 936, 'end': 939, 'mesh': 'D004052'}, {'text': 'PB', 'type': 'Chemical', 'start': 942, 'end': 944, 'mesh': 'D010634'}, {'text': 'tumor', 'type': 'Disease', 'start': 994, 'end': 999, 'mesh': 'D009369'}, {'text': 'DEN', 'type': 'Chemical', 'start': 1061, 'end': 1064, 'mesh': 'D004052'}, {'text': 'PB', 'type': 'Chemical', 'start': 1093, 'end': 1095, 'mesh': 'D010634'}, {'text': 'carcinogenesis', 'type': 'Disease', 'start': 1112, 'end': 1126, 'mesh': 'D063646'}, {'text': 'DEN', 'type': 'Chemical', 'start': 1155, 'end': 1158, 'mesh': 'D004052'}, {'text': 'DEN', 'type': 'Chemical', 'start': 1231, 'end': 1234, 'mesh': 'D004052'}, {'text': 'precancerous lesions', 'type': 'Disease', 'start': 1324, 'end': 1344, 'mesh': 'D011230'}, {'text': 'PB', 'type': 'Chemical', 'start': 1441, 'end': 1443, 'mesh': 'D010634'}]"
+879,3780697,Post-operative rigidity after fentanyl administration.,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.,"[{'text': 'rigidity', 'type': 'Disease', 'start': 15, 'end': 23, 'mesh': 'D009127'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 30, 'end': 38, 'mesh': 'D005283'}, {'text': 'rigidity', 'type': 'Disease', 'start': 83, 'end': 91, 'mesh': 'D009127'}, {'text': 'respiratory failure', 'type': 'Disease', 'start': 103, 'end': 122, 'mesh': 'D012131'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 219, 'end': 227, 'mesh': 'D005283'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 263, 'end': 271, 'mesh': 'D009270'}]"
+880,3686155,Postpartum psychosis induced by bromocriptine.,"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.","[{'text': 'psychosis', 'type': 'Disease', 'start': 11, 'end': 20, 'mesh': 'D011605'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 32, 'end': 45, 'mesh': 'D001971'}, {'text': 'psychiatric', 'type': 'Disease', 'start': 87, 'end': 98, 'mesh': 'D001523'}, {'text': 'psychosis', 'type': 'Disease', 'start': 133, 'end': 142, 'mesh': 'D011605'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 160, 'end': 173, 'mesh': 'D001971'}, {'text': 'inhibition of lactation', 'type': 'Disease', 'start': 178, 'end': 201, 'mesh': 'D007775'}, {'text': 'Bromocriptine', 'type': 'Chemical', 'start': 203, 'end': 216, 'mesh': 'D001971'}, {'text': 'psychosis', 'type': 'Disease', 'start': 262, 'end': 271, 'mesh': 'D011605'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 307, 'end': 326, 'mesh': 'D010300'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 357, 'end': 370, 'mesh': 'D001971'}, {'text': 'psychosis', 'type': 'Disease', 'start': 381, 'end': 390, 'mesh': 'D011605'}]"
+881,3137399,A prospective study on the dose dependency of cardiotoxicity induced by mitomycin C.,"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.","[{'text': 'cardiotoxicity', 'type': 'Disease', 'start': 46, 'end': 60, 'mesh': 'D066126'}, {'text': 'mitomycin C', 'type': 'Chemical', 'start': 72, 'end': 83, 'mesh': 'D016685'}, {'text': 'mitomycin C', 'type': 'Chemical', 'start': 96, 'end': 107, 'mesh': 'D016685'}, {'text': 'MMC', 'type': 'Chemical', 'start': 109, 'end': 112, 'mesh': 'D016685'}, {'text': 'cardiotoxic', 'type': 'Disease', 'start': 139, 'end': 150, 'mesh': 'D066126'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 201, 'end': 212, 'mesh': 'D004317'}, {'text': 'MMC', 'type': 'Chemical', 'start': 388, 'end': 391, 'mesh': 'D016685'}, {'text': 'cardiac failure', 'type': 'Disease', 'start': 716, 'end': 731, 'mesh': 'D006333'}, {'text': 'MMC', 'type': 'Chemical', 'start': 748, 'end': 751, 'mesh': 'D016685'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 772, 'end': 783, 'mesh': 'D004317'}, {'text': 'cardiac failure', 'type': 'Disease', 'start': 789, 'end': 804, 'mesh': 'D006333'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 920, 'end': 934, 'mesh': 'D066126'}, {'text': 'MMC', 'type': 'Chemical', 'start': 1111, 'end': 1114, 'mesh': 'D016685'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1123, 'end': 1137, 'mesh': 'D066126'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1283, 'end': 1294, 'mesh': 'D004317'}]"
+882,2709684,Phlorizin-induced glycosuria does not prevent gentamicin nephrotoxicity in rats.,"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)","[{'text': 'Phlorizin', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D010695'}, {'text': 'glycosuria', 'type': 'Disease', 'start': 18, 'end': 28, 'mesh': 'D006029'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 46, 'end': 56, 'mesh': 'D005839'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 57, 'end': 71, 'mesh': 'D007674'}, {'text': 'streptozotocin', 'type': 'Chemical', 'start': 99, 'end': 113, 'mesh': 'D013311'}, {'text': 'diabetes mellitus', 'type': 'Disease', 'start': 122, 'end': 139, 'mesh': 'D003920'}, {'text': 'DM', 'type': 'Disease', 'start': 141, 'end': 143, 'mesh': 'D003920'}, {'text': 'glycosuria', 'type': 'Disease', 'start': 174, 'end': 184, 'mesh': 'D006029'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 284, 'end': 294, 'mesh': 'D005839'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 303, 'end': 322, 'mesh': 'D058186'}, {'text': 'ARF', 'type': 'Disease', 'start': 324, 'end': 327, 'mesh': 'D058186'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 350, 'end': 360, 'mesh': 'D005839'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 361, 'end': 375, 'mesh': 'D007674'}, {'text': 'diabetic', 'type': 'Disease', 'start': 395, 'end': 403, 'mesh': 'D003920'}, {'text': 'glucose', 'type': 'Chemical', 'start': 469, 'end': 476, 'mesh': 'D005947'}, {'text': 'phlorizin', 'type': 'Chemical', 'start': 495, 'end': 504, 'mesh': 'D010695'}, {'text': 'P', 'type': 'Chemical', 'start': 506, 'end': 507, 'mesh': 'D010695'}, {'text': 'DM', 'type': 'Disease', 'start': 510, 'end': 512, 'mesh': 'D003920'}, {'text': 'glycosuria', 'type': 'Disease', 'start': 528, 'end': 538, 'mesh': 'D006029'}, {'text': 'P', 'type': 'Chemical', 'start': 573, 'end': 574, 'mesh': 'D010695'}, {'text': 'P', 'type': 'Chemical', 'start': 722, 'end': 723, 'mesh': 'D010695'}, {'text': 'P', 'type': 'Chemical', 'start': 740, 'end': 741, 'mesh': 'D010695'}, {'text': 'P', 'type': 'Chemical', 'start': 778, 'end': 779, 'mesh': 'D010695'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 782, 'end': 792, 'mesh': 'D005839'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 806, 'end': 816, 'mesh': 'D005839'}, {'text': 'DM', 'type': 'Disease', 'start': 843, 'end': 845, 'mesh': 'D003920'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 848, 'end': 858, 'mesh': 'D005839'}, {'text': 'Nephrotoxic', 'type': 'Disease', 'start': 861, 'end': 872, 'mesh': 'D007674'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 905, 'end': 915, 'mesh': 'D005839'}, {'text': 'P', 'type': 'Chemical', 'start': 1012, 'end': 1013, 'mesh': 'D010695'}, {'text': 'glycosuria', 'type': 'Disease', 'start': 1044, 'end': 1054, 'mesh': 'D006029'}, {'text': 'renal dysfunction', 'type': 'Disease', 'start': 1125, 'end': 1142, 'mesh': 'D007674'}, {'text': 'tubular necrosis', 'type': 'Disease', 'start': 1214, 'end': 1230, 'mesh': 'D009956'}, {'text': 'P', 'type': 'Chemical', 'start': 1270, 'end': 1271, 'mesh': 'D010695'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 1288, 'end': 1298, 'mesh': 'D005839'}, {'text': 'ARF', 'type': 'Disease', 'start': 1299, 'end': 1302, 'mesh': 'D058186'}, {'text': 'P', 'type': 'Chemical', 'start': 1342, 'end': 1343, 'mesh': 'D010695'}, {'text': 'tubular necrosis', 'type': 'Disease', 'start': 1412, 'end': 1428, 'mesh': 'D009956'}, {'text': 'P', 'type': 'Chemical', 'start': 1536, 'end': 1537, 'mesh': 'D010695'}, {'text': 'tubular necrosis', 'type': 'Disease', 'start': 1598, 'end': 1614, 'mesh': 'D009956'}]"
+883,458486,Tiapride in levodopa-induced involuntary movements.,"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.","[{'text': 'Tiapride', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D063325'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 12, 'end': 20, 'mesh': 'D007980'}, {'text': 'involuntary movements', 'type': 'Disease', 'start': 29, 'end': 50, 'mesh': 'D004409'}, {'text': 'Tiapride', 'type': 'Chemical', 'start': 52, 'end': 60, 'mesh': 'D063325'}, {'text': 'benzamide', 'type': 'Chemical', 'start': 76, 'end': 85, 'mesh': 'C037689'}, {'text': 'metoclopramide', 'type': 'Chemical', 'start': 116, 'end': 130, 'mesh': 'D008787'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 140, 'end': 148, 'mesh': 'D007980'}, {'text': 'involuntary movements', 'type': 'Disease', 'start': 167, 'end': 188, 'mesh': 'D004409'}, {'text': ""idiopathic Parkinson's disease"", 'type': 'Disease', 'start': 209, 'end': 239, 'mesh': 'D010300'}, {'text': 'Parkinsonism', 'type': 'Disease', 'start': 294, 'end': 306, 'mesh': 'D010300'}, {'text': 'akinesia', 'type': 'Disease', 'start': 339, 'end': 347, 'mesh': 'D004409'}, {'text': 'Tiapride', 'type': 'Chemical', 'start': 385, 'end': 393, 'mesh': 'D063325'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 411, 'end': 419, 'mesh': 'D007980'}, {'text': 'dystonia', 'type': 'Disease', 'start': 468, 'end': 476, 'mesh': 'D004421'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 524, 'end': 532, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 541, 'end': 552, 'mesh': 'D004409'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 606, 'end': 614, 'mesh': 'D004298'}]"
+884,21294084,Effects of the hippocampal deep brain stimulation on cortical epileptic discharges in penicillin - induced epilepsy model in rats.,"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.","[{'text': 'epileptic', 'type': 'Disease', 'start': 62, 'end': 71, 'mesh': 'D004827'}, {'text': 'penicillin', 'type': 'Chemical', 'start': 86, 'end': 96, 'mesh': 'D010406'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 107, 'end': 115, 'mesh': 'D004827'}, {'text': 'epileptic', 'type': 'Disease', 'start': 217, 'end': 226, 'mesh': 'D004827'}, {'text': 'epileptic', 'type': 'Disease', 'start': 426, 'end': 435, 'mesh': 'D004827'}, {'text': 'penicillin', 'type': 'Chemical', 'start': 448, 'end': 458, 'mesh': 'D010406'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 467, 'end': 475, 'mesh': 'D004827'}, {'text': 'penicillin G', 'type': 'Chemical', 'start': 711, 'end': 723, 'mesh': 'D010400'}, {'text': 'penicillin-G', 'type': 'Chemical', 'start': 905, 'end': 917, 'mesh': 'D010400'}, {'text': 'penicillin', 'type': 'Chemical', 'start': 1101, 'end': 1111, 'mesh': 'D010406'}, {'text': 'epileptic', 'type': 'Disease', 'start': 1129, 'end': 1138, 'mesh': 'D004827'}, {'text': 'epileptic', 'type': 'Disease', 'start': 1441, 'end': 1450, 'mesh': 'D004827'}, {'text': 'epileptic', 'type': 'Disease', 'start': 1498, 'end': 1507, 'mesh': 'D004827'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 1628, 'end': 1636, 'mesh': 'D004827'}]"
+885,20727411,Neural correlates of S-ketamine induced psychosis during overt continuous verbal fluency.,"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.","[{'text': 'S-ketamine', 'type': 'Chemical', 'start': 21, 'end': 31, 'mesh': '-1'}, {'text': 'psychosis', 'type': 'Disease', 'start': 40, 'end': 49, 'mesh': 'D011605'}, {'text': 'N-methyl-D-aspartate', 'type': 'Chemical', 'start': 108, 'end': 128, 'mesh': 'D016202'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 130, 'end': 134, 'mesh': 'D016202'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 191, 'end': 204, 'mesh': 'D012559'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 286, 'end': 290, 'mesh': 'D016202'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 311, 'end': 319, 'mesh': 'D007649'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 386, 'end': 399, 'mesh': 'D012559'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 418, 'end': 431, 'mesh': 'D012559'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 433, 'end': 441, 'mesh': 'D007649'}, {'text': 'glutamatergic dysfunction', 'type': 'Disease', 'start': 515, 'end': 540, 'mesh': 'D018754'}, {'text': 'S-ketamine', 'type': 'Chemical', 'start': 673, 'end': 683, 'mesh': '-1'}, {'text': 'Ketamine', 'type': 'Chemical', 'start': 886, 'end': 894, 'mesh': 'D007649'}, {'text': 'Ketamine', 'type': 'Chemical', 'start': 1000, 'end': 1008, 'mesh': 'D007649'}, {'text': 'psychosis', 'type': 'Disease', 'start': 1018, 'end': 1027, 'mesh': 'D011605'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 1120, 'end': 1128, 'mesh': 'D007649'}, {'text': 'Ketamine', 'type': 'Chemical', 'start': 1259, 'end': 1267, 'mesh': 'D007649'}, {'text': 'Ketamine', 'type': 'Chemical', 'start': 1430, 'end': 1438, 'mesh': 'D007649'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 1529, 'end': 1542, 'mesh': 'D012559'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 1657, 'end': 1661, 'mesh': 'D016202'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 1709, 'end': 1722, 'mesh': 'D012559'}]"
+886,20533999,Dopamine is not essential for the development of methamphetamine-induced neurotoxicity.,"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.","[{'text': 'Dopamine', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D004298'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 49, 'end': 64, 'mesh': 'D008694'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 73, 'end': 86, 'mesh': 'D020258'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 115, 'end': 123, 'mesh': 'D004298'}, {'text': 'DA', 'type': 'Chemical', 'start': 125, 'end': 127, 'mesh': 'D004298'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 138, 'end': 153, 'mesh': 'D008694'}, {'text': 'METH', 'type': 'Chemical', 'start': 155, 'end': 159, 'mesh': 'D008694'}, {'text': 'toxicity', 'type': 'Disease', 'start': 169, 'end': 177, 'mesh': 'D064420'}, {'text': 'DA', 'type': 'Chemical', 'start': 243, 'end': 245, 'mesh': 'D004298'}, {'text': 'toxicity', 'type': 'Disease', 'start': 273, 'end': 281, 'mesh': 'D064420'}, {'text': 'DA', 'type': 'Chemical', 'start': 311, 'end': 313, 'mesh': 'D004298'}, {'text': 'toxicity', 'type': 'Disease', 'start': 340, 'end': 348, 'mesh': 'D064420'}, {'text': 'DA', 'type': 'Chemical', 'start': 428, 'end': 430, 'mesh': 'D004298'}, {'text': 'L-dihydroxyphenylalanine', 'type': 'Chemical', 'start': 537, 'end': 561, 'mesh': 'D007980'}, {'text': 'alpha-methyl-para-tyrosine', 'type': 'Chemical', 'start': 598, 'end': 624, 'mesh': 'D019805'}, {'text': 'METH', 'type': 'Chemical', 'start': 628, 'end': 632, 'mesh': 'D008694'}, {'text': 'DA', 'type': 'Chemical', 'start': 641, 'end': 643, 'mesh': 'D004298'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 644, 'end': 657, 'mesh': 'D020258'}, {'text': 'DA', 'type': 'Chemical', 'start': 789, 'end': 791, 'mesh': 'D004298'}, {'text': 'METH', 'type': 'Chemical', 'start': 800, 'end': 804, 'mesh': 'D008694'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 805, 'end': 818, 'mesh': 'D020258'}, {'text': 'METH', 'type': 'Chemical', 'start': 854, 'end': 858, 'mesh': 'D008694'}, {'text': 'DA', 'type': 'Chemical', 'start': 960, 'end': 962, 'mesh': 'D004298'}, {'text': 'METH', 'type': 'Chemical', 'start': 980, 'end': 984, 'mesh': 'D008694'}, {'text': 'dopaminergic deficits', 'type': 'Disease', 'start': 993, 'end': 1014, 'mesh': 'D009461'}, {'text': 'DA', 'type': 'Chemical', 'start': 1124, 'end': 1126, 'mesh': 'D004298'}, {'text': 'METH', 'type': 'Chemical', 'start': 1167, 'end': 1171, 'mesh': 'D008694'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 1193, 'end': 1206, 'mesh': 'D020258'}, {'text': 'DA', 'type': 'Chemical', 'start': 1250, 'end': 1252, 'mesh': 'D004298'}]"
+887,20304337,Brainstem dysgenesis in an infant prenatally exposed to cocaine.,"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.","[{'text': 'Brainstem dysgenesis', 'type': 'Disease', 'start': 0, 'end': 20, 'mesh': '-1'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 56, 'end': 63, 'mesh': 'D003042'}, {'text': 'cocaine abuse', 'type': 'Disease', 'start': 125, 'end': 138, 'mesh': 'D019970'}, {'text': 'fetal anomalies', 'type': 'Disease', 'start': 246, 'end': 261, 'mesh': 'D005315'}, {'text': 'multiple cranial-nerve involvement', 'type': 'Disease', 'start': 291, 'end': 325, 'mesh': 'D003389'}, {'text': 'brainstem dysgenesis', 'type': 'Disease', 'start': 342, 'end': 362, 'mesh': '-1'}, {'text': 'cocaine-addicted', 'type': 'Disease', 'start': 374, 'end': 390, 'mesh': 'D019970'}]"
+888,20103708,The protective role of Nrf2 in streptozotocin-induced diabetic nephropathy.,"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.","[{'text': 'streptozotocin', 'type': 'Chemical', 'start': 31, 'end': 45, 'mesh': 'D013311'}, {'text': 'diabetic nephropathy', 'type': 'Disease', 'start': 54, 'end': 74, 'mesh': 'D003928'}, {'text': 'Diabetic nephropathy', 'type': 'Disease', 'start': 87, 'end': 107, 'mesh': 'D003928'}, {'text': 'renal failure', 'type': 'Disease', 'start': 138, 'end': 151, 'mesh': 'D051437'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 204, 'end': 210, 'mesh': 'D010100'}, {'text': 'diabetic nephropathy', 'type': 'Disease', 'start': 437, 'end': 457, 'mesh': 'D003928'}, {'text': 'diabetic nephropathy', 'type': 'Disease', 'start': 535, 'end': 555, 'mesh': 'D003928'}, {'text': 'diabetic nephropathy', 'type': 'Disease', 'start': 595, 'end': 615, 'mesh': 'D003928'}, {'text': 'streptozotocin', 'type': 'Chemical', 'start': 628, 'end': 642, 'mesh': 'D013311'}, {'text': 'diabetic nephropathy', 'type': 'Disease', 'start': 651, 'end': 671, 'mesh': 'D003928'}, {'text': 'diabetic nephropathy', 'type': 'Disease', 'start': 765, 'end': 785, 'mesh': 'D003928'}, {'text': 'streptozotocin', 'type': 'Chemical', 'start': 926, 'end': 940, 'mesh': 'D013311'}, {'text': 'renal damage', 'type': 'Disease', 'start': 949, 'end': 961, 'mesh': 'D058186'}, {'text': 'renal injury', 'type': 'Disease', 'start': 1078, 'end': 1090, 'mesh': 'D058186'}, {'text': 'diabetic nephropathy', 'type': 'Disease', 'start': 1227, 'end': 1247, 'mesh': 'D003928'}, {'text': 'glucose', 'type': 'Chemical', 'start': 1426, 'end': 1433, 'mesh': 'D005947'}, {'text': 'diabetic nephropathy', 'type': 'Disease', 'start': 1805, 'end': 1825, 'mesh': 'D003928'}, {'text': 'diabetic nephropathy', 'type': 'Disease', 'start': 1956, 'end': 1976, 'mesh': 'D003928'}]"
+889,19996135,High-dose tranexamic Acid is associated with nonischemic clinical seizures in cardiac surgical patients.,"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.","[{'text': 'tranexamic Acid', 'type': 'Chemical', 'start': 10, 'end': 25, 'mesh': 'D014148'}, {'text': 'seizures', 'type': 'Disease', 'start': 66, 'end': 74, 'mesh': 'D012640'}, {'text': 'convulsive', 'type': 'Disease', 'start': 205, 'end': 215, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 216, 'end': 224, 'mesh': 'D012640'}, {'text': 'tranexamic acid', 'type': 'Chemical', 'start': 381, 'end': 396, 'mesh': 'D014148'}, {'text': 'TXA', 'type': 'Chemical', 'start': 398, 'end': 401, 'mesh': 'D014148'}, {'text': 'TXA', 'type': 'Chemical', 'start': 585, 'end': 588, 'mesh': 'D014148'}, {'text': 'seizures', 'type': 'Disease', 'start': 599, 'end': 607, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 727, 'end': 735, 'mesh': 'D012640'}, {'text': 'cerebral ischemic injury', 'type': 'Disease', 'start': 957, 'end': 981, 'mesh': 'D001930'}, {'text': 'seizures', 'type': 'Disease', 'start': 987, 'end': 995, 'mesh': 'D012640'}, {'text': 'ischemic brain injury', 'type': 'Disease', 'start': 1015, 'end': 1036, 'mesh': 'D001930'}, {'text': 'seizures', 'type': 'Disease', 'start': 1070, 'end': 1078, 'mesh': 'D012640'}, {'text': 'neurological abnormalities', 'type': 'Disease', 'start': 1102, 'end': 1128, 'mesh': 'D009422'}, {'text': 'seizures', 'type': 'Disease', 'start': 1151, 'end': 1159, 'mesh': 'D012640'}, {'text': 'TXA', 'type': 'Chemical', 'start': 1183, 'end': 1186, 'mesh': 'D014148'}, {'text': 'brain ischemic', 'type': 'Disease', 'start': 1422, 'end': 1436, 'mesh': 'D002546'}, {'text': 'hyperthermia', 'type': 'Disease', 'start': 1452, 'end': 1464, 'mesh': 'D005334'}, {'text': 'seizures', 'type': 'Disease', 'start': 1490, 'end': 1498, 'mesh': 'D012640'}, {'text': 'TXA', 'type': 'Chemical', 'start': 1567, 'end': 1570, 'mesh': 'D014148'}, {'text': 'seizures', 'type': 'Disease', 'start': 1693, 'end': 1701, 'mesh': 'D012640'}]"
+890,19674115,Recurrent dysosmia induced by pyrazinamide.,"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.","[{'text': 'dysosmia', 'type': 'Disease', 'start': 10, 'end': 18, 'mesh': 'D000857'}, {'text': 'pyrazinamide', 'type': 'Chemical', 'start': 30, 'end': 42, 'mesh': 'D011718'}, {'text': 'Pyrazinamide', 'type': 'Chemical', 'start': 44, 'end': 56, 'mesh': 'D011718'}, {'text': 'hepatic toxicity', 'type': 'Disease', 'start': 90, 'end': 106, 'mesh': 'D056486'}, {'text': 'hyperuricemia', 'type': 'Disease', 'start': 108, 'end': 121, 'mesh': 'D033461'}, {'text': 'pyrazinamide', 'type': 'Chemical', 'start': 224, 'end': 236, 'mesh': 'D011718'}, {'text': 'olfactory disorder', 'type': 'Disease', 'start': 300, 'end': 318, 'mesh': 'D000857'}, {'text': 'pyrazinamide', 'type': 'Chemical', 'start': 330, 'end': 342, 'mesh': 'D011718'}, {'text': 'Dysosmia', 'type': 'Disease', 'start': 484, 'end': 492, 'mesh': 'D000857'}, {'text': 'pyrazinamide', 'type': 'Chemical', 'start': 522, 'end': 534, 'mesh': 'D011718'}]"
+891,19139001,Longitudinal assessment of air conduction audiograms in a phase III clinical trial of difluoromethylornithine and sulindac for prevention of sporadic colorectal adenomas.,"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.","[{'text': 'difluoromethylornithine', 'type': 'Chemical', 'start': 86, 'end': 109, 'mesh': 'D000518'}, {'text': 'sulindac', 'type': 'Chemical', 'start': 114, 'end': 122, 'mesh': 'D013467'}, {'text': 'colorectal adenomas', 'type': 'Disease', 'start': 150, 'end': 169, 'mesh': 'D015179'}, {'text': 'adenomatous polyps', 'type': 'Disease', 'start': 225, 'end': 243, 'mesh': 'D018256'}, {'text': 'difluoromethylornithine', 'type': 'Chemical', 'start': 279, 'end': 302, 'mesh': 'D000518'}, {'text': 'DFMO', 'type': 'Chemical', 'start': 304, 'end': 308, 'mesh': 'D000518'}, {'text': 'sulindac', 'type': 'Chemical', 'start': 315, 'end': 323, 'mesh': 'D013467'}, {'text': 'hearing loss', 'type': 'Disease', 'start': 355, 'end': 367, 'mesh': 'D034381'}, {'text': 'toxicity', 'type': 'Disease', 'start': 379, 'end': 387, 'mesh': 'D064420'}, {'text': 'DFMO', 'type': 'Chemical', 'start': 406, 'end': 410, 'mesh': 'D000518'}, {'text': 'DFMO', 'type': 'Chemical', 'start': 847, 'end': 851, 'mesh': 'D000518'}, {'text': 'sulindac', 'type': 'Chemical', 'start': 857, 'end': 865, 'mesh': 'D013467'}, {'text': 'DFMO', 'type': 'Chemical', 'start': 1224, 'end': 1228, 'mesh': 'D000518'}, {'text': 'sulindac', 'type': 'Chemical', 'start': 1234, 'end': 1242, 'mesh': 'D013467'}, {'text': 'DFMO', 'type': 'Chemical', 'start': 1698, 'end': 1702, 'mesh': 'D000518'}, {'text': 'sulindac', 'type': 'Chemical', 'start': 1708, 'end': 1716, 'mesh': 'D013467'}, {'text': 'hearing loss', 'type': 'Disease', 'start': 1762, 'end': 1774, 'mesh': 'D034381'}, {'text': 'ototoxicity', 'type': 'Disease', 'start': 1843, 'end': 1854, 'mesh': 'D006311'}, {'text': 'DFMO', 'type': 'Chemical', 'start': 2014, 'end': 2018, 'mesh': 'D000518'}, {'text': 'sulindac', 'type': 'Chemical', 'start': 2024, 'end': 2032, 'mesh': 'D013467'}]"
+892,18239197,Increased mental slowing associated with the APOE epsilon4 allele after trihexyphenidyl oral anticholinergic challenge in healthy elderly.,"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.","[{'text': 'mental slowing', 'type': 'Disease', 'start': 10, 'end': 24, 'mesh': 'D003072'}, {'text': 'trihexyphenidyl', 'type': 'Chemical', 'start': 72, 'end': 87, 'mesh': 'D014282'}, {'text': 'trihexyphenidyl', 'type': 'Chemical', 'start': 261, 'end': 276, 'mesh': 'D014282'}, {'text': 'confusion', 'type': 'Disease', 'start': 313, 'end': 322, 'mesh': 'D003221'}, {'text': 'trihexyphenidyl', 'type': 'Chemical', 'start': 367, 'end': 382, 'mesh': 'D014282'}, {'text': 'trihexyphenidyl', 'type': 'Chemical', 'start': 744, 'end': 759, 'mesh': 'D014282'}, {'text': 'trihexyphenidyl', 'type': 'Chemical', 'start': 1093, 'end': 1108, 'mesh': 'D014282'}, {'text': 'mental slowness', 'type': 'Disease', 'start': 1153, 'end': 1168, 'mesh': 'D003072'}, {'text': 'trihexyphenidyl', 'type': 'Chemical', 'start': 1278, 'end': 1293, 'mesh': 'D014282'}, {'text': 'mental slowness', 'type': 'Disease', 'start': 1320, 'end': 1335, 'mesh': 'D003072'}, {'text': 'mental slowing', 'type': 'Disease', 'start': 1697, 'end': 1711, 'mesh': 'D003072'}, {'text': 'trihexyphenidyl', 'type': 'Chemical', 'start': 1718, 'end': 1733, 'mesh': 'D014282'}]"
+893,17194457,Behavioral effects of pubertal anabolic androgenic steroid exposure in male rats with low serotonin.,"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.","[{'text': 'steroid', 'type': 'Chemical', 'start': 51, 'end': 58, 'mesh': 'D013256'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 90, 'end': 99, 'mesh': 'D012701'}, {'text': 'steroid', 'type': 'Chemical', 'start': 193, 'end': 200, 'mesh': 'D013256'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 226, 'end': 235, 'mesh': 'D012701'}, {'text': '5-hydroxytryptamine', 'type': 'Chemical', 'start': 237, 'end': 256, 'mesh': 'D012701'}, {'text': '5-HT', 'type': 'Chemical', 'start': 258, 'end': 262, 'mesh': 'D012701'}, {'text': 'Serotonin', 'type': 'Chemical', 'start': 309, 'end': 318, 'mesh': 'D012701'}, {'text': 'parachlorophenylalanine', 'type': 'Chemical', 'start': 367, 'end': 390, 'mesh': '-1'}, {'text': 'PCPA', 'type': 'Chemical', 'start': 392, 'end': 396, 'mesh': '-1'}, {'text': 'PCPA', 'type': 'Chemical', 'start': 479, 'end': 483, 'mesh': '-1'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 551, 'end': 563, 'mesh': 'D013739'}, {'text': 'T', 'type': 'Chemical', 'start': 565, 'end': 566, 'mesh': 'D013739'}, {'text': 'irritability', 'type': 'Disease', 'start': 632, 'end': 644, 'mesh': 'D001523'}, {'text': 'aggression', 'type': 'Disease', 'start': 682, 'end': 692, 'mesh': 'D001523'}, {'text': 'aggression', 'type': 'Disease', 'start': 718, 'end': 728, 'mesh': 'D001523'}, {'text': '5-HT', 'type': 'Chemical', 'start': 827, 'end': 831, 'mesh': 'D012701'}, {'text': '5-hydroxyindoleacetic acid', 'type': 'Chemical', 'start': 852, 'end': 878, 'mesh': 'D006897'}, {'text': '5-HIAA', 'type': 'Chemical', 'start': 880, 'end': 886, 'mesh': 'D006897'}, {'text': 'PCPA', 'type': 'Chemical', 'start': 917, 'end': 921, 'mesh': '-1'}, {'text': '5-HT', 'type': 'Chemical', 'start': 963, 'end': 967, 'mesh': 'D012701'}, {'text': '5-HIAA', 'type': 'Chemical', 'start': 972, 'end': 978, 'mesh': 'D006897'}, {'text': 'T', 'type': 'Chemical', 'start': 1018, 'end': 1019, 'mesh': 'D013739'}, {'text': '5-HT', 'type': 'Chemical', 'start': 1054, 'end': 1058, 'mesh': 'D012701'}, {'text': '5-HIAA', 'type': 'Chemical', 'start': 1063, 'end': 1069, 'mesh': 'D006897'}, {'text': 'PCPA', 'type': 'Chemical', 'start': 1127, 'end': 1131, 'mesh': '-1'}, {'text': 'PCPA', 'type': 'Chemical', 'start': 1153, 'end': 1157, 'mesh': '-1'}, {'text': 'irritability', 'type': 'Disease', 'start': 1221, 'end': 1233, 'mesh': 'D001523'}, {'text': 'aggression', 'type': 'Disease', 'start': 1295, 'end': 1305, 'mesh': 'D001523'}, {'text': 'T', 'type': 'Chemical', 'start': 1307, 'end': 1308, 'mesh': 'D013739'}, {'text': 'irritability', 'type': 'Disease', 'start': 1344, 'end': 1356, 'mesh': 'D001523'}, {'text': 'aggression', 'type': 'Disease', 'start': 1414, 'end': 1424, 'mesh': 'D001523'}, {'text': 'T', 'type': 'Chemical', 'start': 1464, 'end': 1465, 'mesh': 'D013739'}, {'text': 'PCPA', 'type': 'Chemical', 'start': 1466, 'end': 1470, 'mesh': '-1'}, {'text': '5-HT', 'type': 'Chemical', 'start': 1706, 'end': 1710, 'mesh': 'D012701'}, {'text': 'aggressive behavior', 'type': 'Disease', 'start': 1746, 'end': 1765, 'mesh': 'D001523'}]"
+894,16132524,Intracavitary chemotherapy (paclitaxel/carboplatin liquid crystalline cubic phases) for recurrent glioblastoma -- clinical observations.,"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.","[{'text': 'paclitaxel', 'type': 'Chemical', 'start': 28, 'end': 38, 'mesh': 'D017239'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 39, 'end': 50, 'mesh': 'D016190'}, {'text': 'glioblastoma', 'type': 'Disease', 'start': 98, 'end': 110, 'mesh': 'D005909'}, {'text': 'brain tumors', 'type': 'Disease', 'start': 153, 'end': 165, 'mesh': 'D001932'}, {'text': 'glioblastoma', 'type': 'Disease', 'start': 478, 'end': 490, 'mesh': 'D005909'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 595, 'end': 605, 'mesh': 'D017239'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 610, 'end': 621, 'mesh': 'D016190'}, {'text': 'glioblastoma', 'type': 'Disease', 'start': 747, 'end': 759, 'mesh': 'D005909'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 839, 'end': 849, 'mesh': 'D017239'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 854, 'end': 865, 'mesh': 'D016190'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 946, 'end': 956, 'mesh': 'D017239'}, {'text': 'brain edema', 'type': 'Disease', 'start': 994, 'end': 1005, 'mesh': 'D001929'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 1067, 'end': 1077, 'mesh': 'D017239'}, {'text': 'brain edema', 'type': 'Disease', 'start': 1100, 'end': 1111, 'mesh': 'D001929'}, {'text': 'glioblastoma', 'type': 'Disease', 'start': 1194, 'end': 1206, 'mesh': 'D005909'}]"
+895,12907924,Methylphenidate-induced obsessive-compulsive symptoms in an elderly man.,"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.","[{'text': 'Methylphenidate', 'type': 'Chemical', 'start': 0, 'end': 15, 'mesh': 'D008774'}, {'text': 'obsessive-compulsive symptoms', 'type': 'Disease', 'start': 24, 'end': 53, 'mesh': 'D009771'}, {'text': 'treatment-resistant depression', 'type': 'Disease', 'start': 97, 'end': 127, 'mesh': 'D061218'}, {'text': ""Alzheimer's disease"", 'type': 'Disease', 'start': 138, 'end': 157, 'mesh': 'D000544'}, {'text': 'methylphenidate', 'type': 'Chemical', 'start': 173, 'end': 188, 'mesh': 'D008774'}, {'text': 'obsessive-compulsive behavior', 'type': 'Disease', 'start': 202, 'end': 231, 'mesh': 'D009771'}, {'text': 'methylphenidate', 'type': 'Chemical', 'start': 278, 'end': 293, 'mesh': 'D008774'}, {'text': 'fluvoxamine', 'type': 'Chemical', 'start': 310, 'end': 321, 'mesh': 'D016666'}, {'text': 'psychiatric', 'type': 'Disease', 'start': 348, 'end': 359, 'mesh': 'D001523'}, {'text': 'obsessive-compulsive disorder', 'type': 'Disease', 'start': 394, 'end': 423, 'mesh': 'D009771'}, {'text': 'methylphenidate', 'type': 'Chemical', 'start': 441, 'end': 456, 'mesh': 'D008774'}]"
+896,12139551,Cardiac arrest after intravenous metoclopramide - a case of five repeated injections of metoclopramide causing five episodes of cardiac arrest.,"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.","[{'text': 'Cardiac arrest', 'type': 'Disease', 'start': 0, 'end': 14, 'mesh': 'D006323'}, {'text': 'metoclopramide', 'type': 'Chemical', 'start': 33, 'end': 47, 'mesh': 'D008787'}, {'text': 'metoclopramide', 'type': 'Chemical', 'start': 88, 'end': 102, 'mesh': 'D008787'}, {'text': 'cardiac arrest', 'type': 'Disease', 'start': 128, 'end': 142, 'mesh': 'D006323'}, {'text': 'metoclopramide', 'type': 'Chemical', 'start': 197, 'end': 211, 'mesh': 'D008787'}, {'text': 'asystole', 'type': 'Disease', 'start': 240, 'end': 248, 'mesh': 'D006323'}, {'text': 'metoclopramide', 'type': 'Chemical', 'start': 282, 'end': 296, 'mesh': 'D008787'}, {'text': 'metoclopramide', 'type': 'Chemical', 'start': 454, 'end': 468, 'mesh': 'D008787'}, {'text': 'asystole', 'type': 'Disease', 'start': 508, 'end': 516, 'mesh': 'D006323'}, {'text': 'asystole', 'type': 'Disease', 'start': 522, 'end': 530, 'mesh': 'D006323'}, {'text': 'atropine', 'type': 'Chemical', 'start': 619, 'end': 627, 'mesh': 'D001285'}, {'text': 'cardiac arrest', 'type': 'Disease', 'start': 731, 'end': 745, 'mesh': 'D006323'}, {'text': 'metoclopramide', 'type': 'Chemical', 'start': 756, 'end': 770, 'mesh': 'D008787'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 853, 'end': 861, 'mesh': 'D004298'}]"
+897,10411803,Severe immune hemolytic anemia associated with prophylactic use of cefotetan in obstetric and gynecologic procedures.,"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.","[{'text': 'hemolytic anemia', 'type': 'Disease', 'start': 14, 'end': 30, 'mesh': 'D000743'}, {'text': 'cefotetan', 'type': 'Chemical', 'start': 67, 'end': 76, 'mesh': 'D015313'}, {'text': 'cephalosporins', 'type': 'Chemical', 'start': 147, 'end': 161, 'mesh': 'D002511'}, {'text': 'cefotetan', 'type': 'Chemical', 'start': 174, 'end': 183, 'mesh': 'D015313'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 249, 'end': 265, 'mesh': 'D000743'}, {'text': 'cefotetan', 'type': 'Chemical', 'start': 305, 'end': 314, 'mesh': 'D015313'}, {'text': 'hemolytic anemias', 'type': 'Disease', 'start': 323, 'end': 340, 'mesh': 'D000743'}, {'text': 'cefotetan', 'type': 'Chemical', 'start': 375, 'end': 384, 'mesh': 'D015313'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 482, 'end': 498, 'mesh': 'D000743'}]"
+898,10225068,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.,"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.","[{'text': 'Cauda equina syndrome', 'type': 'Disease', 'start': 0, 'end': 21, 'mesh': 'D011128'}, {'text': 'lignocaine', 'type': 'Chemical', 'start': 66, 'end': 76, 'mesh': 'D008012'}, {'text': 'cauda equina syndrome', 'type': 'Disease', 'start': 103, 'end': 124, 'mesh': 'D011128'}, {'text': 'cauda equina syndrome', 'type': 'Disease', 'start': 198, 'end': 219, 'mesh': 'D011128'}, {'text': 'lignocaine', 'type': 'Chemical', 'start': 389, 'end': 399, 'mesh': 'D008012'}, {'text': 'lignocaine', 'type': 'Chemical', 'start': 538, 'end': 548, 'mesh': 'D008012'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 641, 'end': 654, 'mesh': 'D020258'}, {'text': 'lignocaine', 'type': 'Chemical', 'start': 672, 'end': 682, 'mesh': 'D008012'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 713, 'end': 726, 'mesh': 'D020258'}, {'text': 'neurological deficits', 'type': 'Disease', 'start': 883, 'end': 904, 'mesh': 'D009461'}, {'text': 'lignocaine', 'type': 'Chemical', 'start': 935, 'end': 945, 'mesh': 'D008012'}]"
+899,9549528,Cortical motor overactivation in parkinsonian patients with L-dopa-induced peak-dose dyskinesia.,"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.","[{'text': 'parkinsonian', 'type': 'Disease', 'start': 33, 'end': 45, 'mesh': 'D020734'}, {'text': 'L-dopa', 'type': 'Chemical', 'start': 60, 'end': 66, 'mesh': 'D007980'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 85, 'end': 95, 'mesh': 'D004409'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 292, 'end': 304, 'mesh': 'D020734'}, {'text': 'L-dopa', 'type': 'Chemical', 'start': 317, 'end': 323, 'mesh': 'D007980'}, {'text': 'L-dopa', 'type': 'Chemical', 'start': 358, 'end': 364, 'mesh': 'D007980'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 373, 'end': 383, 'mesh': 'D004409'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 431, 'end': 441, 'mesh': 'D004409'}, {'text': 'dyskinetic', 'type': 'Disease', 'start': 582, 'end': 592, 'mesh': 'D004409'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 593, 'end': 605, 'mesh': 'D020734'}, {'text': 'dyskinetic', 'type': 'Disease', 'start': 718, 'end': 728, 'mesh': 'D004409'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 729, 'end': 741, 'mesh': 'D020734'}, {'text': 'hyperkinetic', 'type': 'Disease', 'start': 928, 'end': 940, 'mesh': 'D006948'}, {'text': 'abnormal involuntary movement', 'type': 'Disease', 'start': 941, 'end': 970, 'mesh': 'D004409'}, {'text': 'L-dopa', 'type': 'Chemical', 'start': 977, 'end': 983, 'mesh': 'D007980'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 1002, 'end': 1012, 'mesh': 'D004409'}]"
+900,7843916,Dexamethasone-induced ocular hypertension in perfusion-cultured human eyes.,"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.","[{'text': 'Dexamethasone', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'D003907'}, {'text': 'ocular hypertension', 'type': 'Disease', 'start': 22, 'end': 41, 'mesh': 'D009798'}, {'text': 'ocular hypertension', 'type': 'Disease', 'start': 146, 'end': 165, 'mesh': 'D009798'}, {'text': 'corticosteroid glaucoma', 'type': 'Disease', 'start': 170, 'end': 193, 'mesh': 'D005901'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 665, 'end': 678, 'mesh': 'D003907'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 1014, 'end': 1027, 'mesh': 'D003907'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 1097, 'end': 1110, 'mesh': 'D003907'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 1175, 'end': 1188, 'mesh': 'D003907'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 1347, 'end': 1360, 'mesh': 'D003907'}, {'text': 'hypertensive eyes', 'type': 'Disease', 'start': 1369, 'end': 1386, 'mesh': 'D009798'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 1696, 'end': 1709, 'mesh': 'D003907'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 1822, 'end': 1835, 'mesh': 'D003907'}, {'text': 'Dexamethasone', 'type': 'Chemical', 'start': 1890, 'end': 1903, 'mesh': 'D003907'}, {'text': 'ocular hypertension', 'type': 'Disease', 'start': 1982, 'end': 2001, 'mesh': 'D009798'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 2030, 'end': 2043, 'mesh': 'D003907'}, {'text': 'Steroid', 'type': 'Chemical', 'start': 2058, 'end': 2065, 'mesh': 'D013256'}, {'text': 'corticosteroid glaucoma', 'type': 'Disease', 'start': 2165, 'end': 2188, 'mesh': 'D005901'}, {'text': 'open angle glaucoma', 'type': 'Disease', 'start': 2193, 'end': 2212, 'mesh': 'D005902'}, {'text': 'steroid glaucoma', 'type': 'Disease', 'start': 2309, 'end': 2325, 'mesh': 'D005901'}, {'text': 'primary open angle glaucoma', 'type': 'Disease', 'start': 2330, 'end': 2357, 'mesh': 'D005902'}]"
+901,7803371,Cognitive deterioration from long-term abuse of dextromethorphan: a case report.,"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.","[{'text': 'Cognitive deterioration', 'type': 'Disease', 'start': 0, 'end': 23, 'mesh': 'D003072'}, {'text': 'dextromethorphan', 'type': 'Chemical', 'start': 48, 'end': 64, 'mesh': 'D003915'}, {'text': 'Dextromethorphan', 'type': 'Chemical', 'start': 81, 'end': 97, 'mesh': 'D003915'}, {'text': 'DM', 'type': 'Chemical', 'start': 99, 'end': 101, 'mesh': 'D003915'}, {'text': '3-hydroxy-N-methylmorphinan', 'type': 'Chemical', 'start': 133, 'end': 160, 'mesh': 'D007981'}, {'text': 'nausea', 'type': 'Disease', 'start': 546, 'end': 552, 'mesh': 'D009325'}, {'text': 'restlessness', 'type': 'Disease', 'start': 554, 'end': 566, 'mesh': 'D011595'}, {'text': 'insomnia', 'type': 'Disease', 'start': 568, 'end': 576, 'mesh': 'D007319'}, {'text': 'ataxia', 'type': 'Disease', 'start': 578, 'end': 584, 'mesh': 'D001259'}, {'text': 'nystagmus', 'type': 'Disease', 'start': 605, 'end': 614, 'mesh': 'C564088'}, {'text': 'aggressive behavior', 'type': 'Disease', 'start': 688, 'end': 707, 'mesh': 'D001523'}, {'text': 'DM', 'type': 'Chemical', 'start': 921, 'end': 923, 'mesh': 'D003915'}, {'text': 'cognitive deterioration', 'type': 'Disease', 'start': 1053, 'end': 1076, 'mesh': 'D003072'}, {'text': 'DM', 'type': 'Chemical', 'start': 1109, 'end': 1111, 'mesh': 'D003915'}]"
+902,7437994,Long-term lithium treatment and the kidney. Interim report on fifty patients.,"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.","[{'text': 'lithium', 'type': 'Chemical', 'start': 10, 'end': 17, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 154, 'end': 161, 'mesh': 'D008094'}, {'text': 'Creatinine', 'type': 'Chemical', 'start': 187, 'end': 197, 'mesh': 'D003404'}, {'text': 'lithium', 'type': 'Chemical', 'start': 336, 'end': 343, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 471, 'end': 478, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 588, 'end': 595, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 704, 'end': 711, 'mesh': 'D008094'}, {'text': 'Polyuria', 'type': 'Disease', 'start': 968, 'end': 976, 'mesh': 'D011141'}]"
+903,6496797,Complete heart block following a single dose of trazodone.,"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.","[{'text': 'heart block', 'type': 'Disease', 'start': 9, 'end': 20, 'mesh': 'D006327'}, {'text': 'trazodone', 'type': 'Chemical', 'start': 48, 'end': 57, 'mesh': 'D014196'}, {'text': 'trazodone', 'type': 'Chemical', 'start': 115, 'end': 124, 'mesh': 'D014196'}, {'text': 'heart block', 'type': 'Disease', 'start': 155, 'end': 166, 'mesh': 'D006327'}, {'text': 'trazodone', 'type': 'Chemical', 'start': 235, 'end': 244, 'mesh': 'D014196'}]"
+904,3411101,Quinidine phenylethylbarbiturate-induced fulminant hepatitis in a pregnant woman. A case report.,"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.","[{'text': 'Quinidine phenylethylbarbiturate', 'type': 'Chemical', 'start': 0, 'end': 32, 'mesh': 'C033457'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 51, 'end': 60, 'mesh': 'D056486'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 171, 'end': 180, 'mesh': 'D056486'}, {'text': 'quinidine phenylethylbarbiturate', 'type': 'Chemical', 'start': 259, 'end': 291, 'mesh': 'C033457'}, {'text': 'Quinidine', 'type': 'Chemical', 'start': 438, 'end': 447, 'mesh': 'D011802'}, {'text': 'phenylethylbarbiturate', 'type': 'Chemical', 'start': 458, 'end': 480, 'mesh': 'C033457'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 514, 'end': 523, 'mesh': 'D056486'}]"
+905,2598570,The epidemiology of the acute flank pain syndrome from suprofen.,"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.","[{'text': 'flank pain', 'type': 'Disease', 'start': 30, 'end': 40, 'mesh': 'D021501'}, {'text': 'suprofen', 'type': 'Chemical', 'start': 55, 'end': 63, 'mesh': 'D013496'}, {'text': 'Suprofen', 'type': 'Chemical', 'start': 65, 'end': 73, 'mesh': 'D013496'}, {'text': 'flank pain', 'type': 'Disease', 'start': 218, 'end': 228, 'mesh': 'D021501'}, {'text': 'suprofen', 'type': 'Chemical', 'start': 583, 'end': 591, 'mesh': 'D013496'}, {'text': 'hay fever', 'type': 'Disease', 'start': 755, 'end': 764, 'mesh': 'D006255'}, {'text': 'asthma', 'type': 'Disease', 'start': 769, 'end': 775, 'mesh': 'D001249'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 986, 'end': 993, 'mesh': 'D000431'}, {'text': 'ibuprofen', 'type': 'Chemical', 'start': 1143, 'end': 1152, 'mesh': 'D007052'}, {'text': 'renal disease', 'type': 'Disease', 'start': 1167, 'end': 1180, 'mesh': 'D007674'}, {'text': 'kidney stones', 'type': 'Disease', 'start': 1195, 'end': 1208, 'mesh': 'D007669'}, {'text': 'gout', 'type': 'Disease', 'start': 1223, 'end': 1227, 'mesh': 'D006073'}, {'text': 'uric acid', 'type': 'Chemical', 'start': 1543, 'end': 1552, 'mesh': 'D014527'}]"
+906,1415380,Hemolytic-uremic syndrome associated with ingestion of quinine.,"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.","[{'text': 'Hemolytic-uremic syndrome', 'type': 'Disease', 'start': 0, 'end': 25, 'mesh': 'D006463'}, {'text': 'quinine', 'type': 'Chemical', 'start': 55, 'end': 62, 'mesh': 'D011803'}, {'text': 'Hemolytic-uremic syndrome', 'type': 'Disease', 'start': 64, 'end': 89, 'mesh': 'D006463'}, {'text': 'quinine', 'type': 'Chemical', 'start': 100, 'end': 107, 'mesh': 'D011803'}, {'text': 'quinine', 'type': 'Chemical', 'start': 346, 'end': 353, 'mesh': 'D011803'}, {'text': 'prednisone', 'type': 'Chemical', 'start': 402, 'end': 412, 'mesh': 'D011241'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 414, 'end': 421, 'mesh': 'D001241'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 427, 'end': 439, 'mesh': 'D004176'}, {'text': 'Quinine', 'type': 'Chemical', 'start': 622, 'end': 629, 'mesh': 'D011803'}, {'text': 'hemolytic-uremic syndrome', 'type': 'Disease', 'start': 641, 'end': 666, 'mesh': 'D006463'}, {'text': 'quinine', 'type': 'Chemical', 'start': 793, 'end': 800, 'mesh': 'D011803'}]"
+907,1255900,Pyeloureteral filling defects associated with systemic anticoagulation: a case report.,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.,"[{'text': 'pyeloureteritis cystica', 'type': 'Disease', 'start': 103, 'end': 126, 'mesh': 'D011702'}, {'text': 'infection', 'type': 'Disease', 'start': 163, 'end': 172, 'mesh': 'D007239'}, {'text': 'inflammation', 'type': 'Disease', 'start': 177, 'end': 189, 'mesh': 'D007249'}, {'text': 'infection', 'type': 'Disease', 'start': 405, 'end': 414, 'mesh': 'D007239'}, {'text': 'heparin', 'type': 'Chemical', 'start': 485, 'end': 492, 'mesh': 'D006493'}, {'text': 'thrombophlebitis', 'type': 'Disease', 'start': 522, 'end': 538, 'mesh': 'D013924'}, {'text': 'pyeloureteritis cystica', 'type': 'Disease', 'start': 692, 'end': 715, 'mesh': 'D011702'}, {'text': 'submucosal hemorrhage', 'type': 'Disease', 'start': 720, 'end': 741, 'mesh': 'D006470'}]"
+908,85485,Changes in peroxisomes in preneoplastic liver and hepatoma of mice induced by alpha-benzene hexachloride.,"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.","[{'text': 'hepatoma', 'type': 'Disease', 'start': 50, 'end': 58, 'mesh': 'D006528'}, {'text': 'alpha-benzene hexachloride', 'type': 'Chemical', 'start': 78, 'end': 104, 'mesh': 'D001556'}, {'text': 'hepatomas', 'type': 'Disease', 'start': 121, 'end': 130, 'mesh': 'D006528'}, {'text': 'liver lesions', 'type': 'Disease', 'start': 162, 'end': 175, 'mesh': 'D017093'}, {'text': 'alpha-benzene hexachloride', 'type': 'Chemical', 'start': 203, 'end': 229, 'mesh': 'D001556'}, {'text': 'hepatomas', 'type': 'Disease', 'start': 311, 'end': 320, 'mesh': 'D006528'}, {'text': 'tumors', 'type': 'Disease', 'start': 346, 'end': 352, 'mesh': 'D009369'}, {'text': 'tumor', 'type': 'Disease', 'start': 409, 'end': 414, 'mesh': 'D009369'}, {'text': 'ethyl-alpha-p-chlorophenoxyisobutyrate', 'type': 'Chemical', 'start': 440, 'end': 478, 'mesh': 'C012282'}, {'text': 'hepatomas', 'type': 'Disease', 'start': 955, 'end': 964, 'mesh': 'D006528'}, {'text': 'ethyl-alpha-p-chlorophenoxyisobutyrate', 'type': 'Chemical', 'start': 1094, 'end': 1132, 'mesh': 'C012282'}]"
+909,48362,Quinidine hepatitis.,"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.","[{'text': 'Quinidine', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D011802'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 10, 'end': 19, 'mesh': 'D056486'}, {'text': 'quinidine', 'type': 'Chemical', 'start': 49, 'end': 58, 'mesh': 'D011802'}, {'text': 'lactic acid', 'type': 'Chemical', 'start': 133, 'end': 144, 'mesh': 'D019344'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 213, 'end': 222, 'mesh': 'D056486'}, {'text': 'quinidine', 'type': 'Chemical', 'start': 242, 'end': 251, 'mesh': 'D011802'}, {'text': 'quinidine', 'type': 'Chemical', 'start': 326, 'end': 335, 'mesh': 'D011802'}, {'text': 'lactic acid', 'type': 'Chemical', 'start': 417, 'end': 428, 'mesh': 'D019344'}, {'text': 'quinidine', 'type': 'Chemical', 'start': 486, 'end': 495, 'mesh': 'D011802'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 496, 'end': 510, 'mesh': 'D056486'}, {'text': 'hepatic toxicity', 'type': 'Disease', 'start': 666, 'end': 682, 'mesh': 'D056486'}]"
+910,9067481,"Cholesteryl hemisuccinate treatment protects rodents from the toxic effects of acetaminophen, adriamycin, carbon tetrachloride, chloroform and galactosamine.","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.","[{'text': 'Cholesteryl hemisuccinate', 'type': 'Chemical', 'start': 0, 'end': 25, 'mesh': 'C013440'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 79, 'end': 92, 'mesh': 'D000082'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 94, 'end': 104, 'mesh': 'D004317'}, {'text': 'carbon tetrachloride', 'type': 'Chemical', 'start': 106, 'end': 126, 'mesh': 'D002251'}, {'text': 'chloroform', 'type': 'Chemical', 'start': 128, 'end': 138, 'mesh': 'D002725'}, {'text': 'galactosamine', 'type': 'Chemical', 'start': 143, 'end': 156, 'mesh': 'D005688'}, {'text': 'cholesteryl hemisuccinate', 'type': 'Chemical', 'start': 222, 'end': 247, 'mesh': 'C013440'}, {'text': 'tris salt', 'type': 'Chemical', 'start': 249, 'end': 258, 'mesh': '-1'}, {'text': 'CS', 'type': 'Chemical', 'start': 260, 'end': 262, 'mesh': '-1'}, {'text': 'hepatotoxic', 'type': 'Disease', 'start': 324, 'end': 335, 'mesh': 'D056486'}, {'text': 'carbon tetrachloride', 'type': 'Chemical', 'start': 347, 'end': 367, 'mesh': 'D002251'}, {'text': 'CCl4', 'type': 'Chemical', 'start': 369, 'end': 373, 'mesh': 'D002251'}, {'text': 'CS', 'type': 'Chemical', 'start': 425, 'end': 427, 'mesh': '-1'}, {'text': 'CS', 'type': 'Chemical', 'start': 501, 'end': 503, 'mesh': '-1'}, {'text': 'CS', 'type': 'Chemical', 'start': 543, 'end': 545, 'mesh': '-1'}, {'text': 'gamma-cholesteryloxybutyric acid', 'type': 'Chemical', 'start': 547, 'end': 579, 'mesh': 'C103872'}, {'text': 'tris salt', 'type': 'Chemical', 'start': 581, 'end': 590, 'mesh': '-1'}, {'text': 'CSE', 'type': 'Chemical', 'start': 592, 'end': 595, 'mesh': '-1'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 605, 'end': 618, 'mesh': 'D000082'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 621, 'end': 631, 'mesh': 'D004317'}, {'text': 'carbon tetrachloride', 'type': 'Chemical', 'start': 634, 'end': 654, 'mesh': 'D002251'}, {'text': 'chloroform', 'type': 'Chemical', 'start': 657, 'end': 667, 'mesh': 'D002725'}, {'text': 'galactosamine', 'type': 'Chemical', 'start': 673, 'end': 686, 'mesh': 'D005688'}, {'text': 'toxicity', 'type': 'Disease', 'start': 695, 'end': 703, 'mesh': 'D064420'}, {'text': 'CS', 'type': 'Chemical', 'start': 752, 'end': 754, 'mesh': '-1'}, {'text': 'CS', 'type': 'Chemical', 'start': 914, 'end': 916, 'mesh': '-1'}, {'text': 'hepatotoxic', 'type': 'Disease', 'start': 982, 'end': 993, 'mesh': 'D056486'}, {'text': 'CCl4', 'type': 'Chemical', 'start': 1005, 'end': 1009, 'mesh': 'D002251'}, {'text': 'CHCl3', 'type': 'Chemical', 'start': 1011, 'end': 1016, 'mesh': 'D002725'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 1018, 'end': 1031, 'mesh': 'D000082'}, {'text': 'galactosamine', 'type': 'Chemical', 'start': 1036, 'end': 1049, 'mesh': 'D005688'}, {'text': 'cardiotoxic', 'type': 'Disease', 'start': 1089, 'end': 1100, 'mesh': 'D066126'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 1112, 'end': 1122, 'mesh': 'D004317'}, {'text': 'CS', 'type': 'Chemical', 'start': 1147, 'end': 1149, 'mesh': '-1'}, {'text': 'CS', 'type': 'Chemical', 'start': 1274, 'end': 1276, 'mesh': '-1'}, {'text': 'CS', 'type': 'Chemical', 'start': 1391, 'end': 1393, 'mesh': '-1'}, {'text': 'galactosamine', 'type': 'Chemical', 'start': 1559, 'end': 1572, 'mesh': 'D005688'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 1573, 'end': 1587, 'mesh': 'D056486'}, {'text': 'CS', 'type': 'Chemical', 'start': 1668, 'end': 1670, 'mesh': '-1'}, {'text': 'CS', 'type': 'Chemical', 'start': 1748, 'end': 1750, 'mesh': '-1'}, {'text': 'CS', 'type': 'Chemical', 'start': 1820, 'end': 1822, 'mesh': '-1'}, {'text': 'CSE', 'type': 'Chemical', 'start': 1850, 'end': 1853, 'mesh': '-1'}, {'text': 'CS', 'type': 'Chemical', 'start': 1875, 'end': 1877, 'mesh': '-1'}]"
+911,19274460,DSMM XI study: dose definition for intravenous cyclophosphamide in combination with bortezomib/dexamethasone for remission induction in patients with newly diagnosed myeloma.,"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.","[{'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 47, 'end': 63, 'mesh': 'D003520'}, {'text': 'bortezomib', 'type': 'Chemical', 'start': 84, 'end': 94, 'mesh': 'C400082'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 95, 'end': 108, 'mesh': 'D003907'}, {'text': 'myeloma', 'type': 'Disease', 'start': 166, 'end': 173, 'mesh': 'D009101'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 242, 'end': 258, 'mesh': 'D003520'}, {'text': 'bortezomib', 'type': 'Chemical', 'start': 279, 'end': 289, 'mesh': 'C400082'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 294, 'end': 307, 'mesh': 'D003907'}, {'text': 'multiple myeloma', 'type': 'Disease', 'start': 406, 'end': 422, 'mesh': 'D009101'}, {'text': 'MM', 'type': 'Disease', 'start': 424, 'end': 426, 'mesh': 'D009101'}, {'text': 'bortezomib', 'type': 'Chemical', 'start': 486, 'end': 496, 'mesh': 'C400082'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 538, 'end': 551, 'mesh': 'D003907'}, {'text': 'bortezomib', 'type': 'Chemical', 'start': 572, 'end': 582, 'mesh': 'C400082'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 616, 'end': 632, 'mesh': 'D003520'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 705, 'end': 721, 'mesh': 'D003520'}, {'text': 'neuropathy', 'type': 'Disease', 'start': 1093, 'end': 1103, 'mesh': 'D009422'}, {'text': 'bortezomib', 'type': 'Chemical', 'start': 1130, 'end': 1140, 'mesh': 'C400082'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 1161, 'end': 1177, 'mesh': 'D003520'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 1197, 'end': 1210, 'mesh': 'D003907'}, {'text': 'MM', 'type': 'Disease', 'start': 1281, 'end': 1283, 'mesh': 'D009101'}]"
+912,18201582,"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.","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.","[{'text': 'telmisartan', 'type': 'Chemical', 'start': 172, 'end': 183, 'mesh': 'C084178'}, {'text': 'amlodipine', 'type': 'Chemical', 'start': 188, 'end': 198, 'mesh': 'D017311'}, {'text': 'amlodipine', 'type': 'Chemical', 'start': 206, 'end': 216, 'mesh': 'D017311'}, {'text': 'hypertension', 'type': 'Disease', 'start': 260, 'end': 272, 'mesh': 'D006973'}, {'text': 'telmisartan', 'type': 'Chemical', 'start': 394, 'end': 405, 'mesh': 'C084178'}, {'text': 'amlodipine', 'type': 'Chemical', 'start': 414, 'end': 424, 'mesh': 'D017311'}, {'text': 'amlodipine', 'type': 'Chemical', 'start': 450, 'end': 460, 'mesh': 'D017311'}, {'text': 'hypertension', 'type': 'Disease', 'start': 521, 'end': 533, 'mesh': 'D006973'}, {'text': 'hypertension', 'type': 'Disease', 'start': 718, 'end': 730, 'mesh': 'D006973'}, {'text': 'edema', 'type': 'Disease', 'start': 1939, 'end': 1944, 'mesh': 'D004487'}, {'text': 'cough', 'type': 'Disease', 'start': 2049, 'end': 2054, 'mesh': 'D003371'}, {'text': 'headache', 'type': 'Disease', 'start': 2228, 'end': 2236, 'mesh': 'D006261'}, {'text': 'dizziness', 'type': 'Disease', 'start': 2238, 'end': 2247, 'mesh': 'D004244'}, {'text': 'diarrhea', 'type': 'Disease', 'start': 2253, 'end': 2261, 'mesh': 'D003967'}, {'text': 'hypertension', 'type': 'Disease', 'start': 2352, 'end': 2364, 'mesh': 'D006973'}]"
+913,11337188,Cutaneous leucocytoclastic vasculitis associated with oxacillin.,"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.","[{'text': 'Cutaneous leucocytoclastic vasculitis', 'type': 'Disease', 'start': 0, 'end': 37, 'mesh': 'D018366'}, {'text': 'oxacillin', 'type': 'Chemical', 'start': 54, 'end': 63, 'mesh': 'D010068'}, {'text': 'oxacillin', 'type': 'Chemical', 'start': 104, 'end': 113, 'mesh': 'D010068'}, {'text': 'renal failure', 'type': 'Disease', 'start': 182, 'end': 195, 'mesh': 'D051437'}, {'text': 'purpuric lesions', 'type': 'Disease', 'start': 229, 'end': 245, 'mesh': 'D011693'}, {'text': 'leucocytoclastic vasculitis', 'type': 'Disease', 'start': 348, 'end': 375, 'mesh': 'D018366'}, {'text': 'Oxacillin', 'type': 'Chemical', 'start': 377, 'end': 386, 'mesh': 'D010068'}, {'text': 'corticosteroids', 'type': 'Chemical', 'start': 433, 'end': 448, 'mesh': 'D000305'}, {'text': 'rash', 'type': 'Disease', 'start': 454, 'end': 458, 'mesh': 'D005076'}, {'text': 'Leucocytoclastic vasculitis', 'type': 'Disease', 'start': 528, 'end': 555, 'mesh': 'D018366'}, {'text': 'purpura', 'type': 'Disease', 'start': 577, 'end': 584, 'mesh': 'D011693'}, {'text': 'abdominal pain', 'type': 'Disease', 'start': 631, 'end': 645, 'mesh': 'D015746'}, {'text': 'arthralgia', 'type': 'Disease', 'start': 647, 'end': 657, 'mesh': 'D018771'}, {'text': 'renal involvement', 'type': 'Disease', 'start': 663, 'end': 680, 'mesh': 'D007674'}, {'text': 'infections', 'type': 'Disease', 'start': 732, 'end': 742, 'mesh': 'D007239'}, {'text': 'collagen vascular disease', 'type': 'Disease', 'start': 757, 'end': 782, 'mesh': 'D003095'}, {'text': 'neoplasia', 'type': 'Disease', 'start': 787, 'end': 796, 'mesh': 'D009369'}, {'text': 'corticosteroid', 'type': 'Chemical', 'start': 906, 'end': 920, 'mesh': 'D000305'}, {'text': 'corticosteroids', 'type': 'Chemical', 'start': 996, 'end': 1011, 'mesh': 'D000305'}, {'text': 'Oxacillin', 'type': 'Chemical', 'start': 1055, 'end': 1064, 'mesh': 'D010068'}, {'text': 'leucocytoclastic vasculitis', 'type': 'Disease', 'start': 1115, 'end': 1142, 'mesh': 'D018366'}]"
+914,6308526,"Naloxazone pretreatment modifies cardiorespiratory, temperature, and behavioral effects of morphine.","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.","[{'text': 'Naloxazone', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'C024224'}, {'text': 'morphine', 'type': 'Chemical', 'start': 91, 'end': 99, 'mesh': 'D009020'}, {'text': 'morphine', 'type': 'Chemical', 'start': 164, 'end': 172, 'mesh': 'D009020'}, {'text': 'naloxazone', 'type': 'Chemical', 'start': 222, 'end': 232, 'mesh': 'C024224'}, {'text': 'naloxazone', 'type': 'Chemical', 'start': 306, 'end': 316, 'mesh': 'C024224'}, {'text': 'morphine', 'type': 'Chemical', 'start': 339, 'end': 347, 'mesh': 'D009020'}, {'text': 'analgesia', 'type': 'Disease', 'start': 348, 'end': 357, 'mesh': 'D000699'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 359, 'end': 368, 'mesh': 'D002375'}, {'text': 'hypothermia', 'type': 'Disease', 'start': 373, 'end': 384, 'mesh': 'D007035'}, {'text': 'naloxazone', 'type': 'Chemical', 'start': 475, 'end': 485, 'mesh': 'C024224'}, {'text': 'morphine', 'type': 'Chemical', 'start': 515, 'end': 523, 'mesh': 'D009020'}, {'text': 'hypotension', 'type': 'Disease', 'start': 532, 'end': 543, 'mesh': 'D007022'}, {'text': 'respiratory depression', 'type': 'Disease', 'start': 548, 'end': 570, 'mesh': 'D012131'}, {'text': 'morphine', 'type': 'Chemical', 'start': 580, 'end': 588, 'mesh': 'D009020'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 597, 'end': 608, 'mesh': 'D001919'}, {'text': 'morphine', 'type': 'Chemical', 'start': 749, 'end': 757, 'mesh': 'D009020'}]"
+915,15897593,Dexrazoxane protects against myelosuppression from the DNA cleavage-enhancing drugs etoposide and daunorubicin but not doxorubicin.,"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.","[{'text': 'Dexrazoxane', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D064730'}, {'text': 'myelosuppression', 'type': 'Disease', 'start': 29, 'end': 45, 'mesh': 'D001855'}, {'text': 'etoposide', 'type': 'Chemical', 'start': 84, 'end': 93, 'mesh': 'D005047'}, {'text': 'daunorubicin', 'type': 'Chemical', 'start': 98, 'end': 110, 'mesh': 'D003630'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 119, 'end': 130, 'mesh': 'D004317'}, {'text': 'anthracyclines', 'type': 'Chemical', 'start': 145, 'end': 159, 'mesh': 'D018943'}, {'text': 'daunorubicin', 'type': 'Chemical', 'start': 160, 'end': 172, 'mesh': 'D003630'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 177, 'end': 188, 'mesh': 'D004317'}, {'text': 'epipodophyllotoxin', 'type': 'Chemical', 'start': 197, 'end': 215, 'mesh': 'D011034'}, {'text': 'etoposide', 'type': 'Chemical', 'start': 216, 'end': 225, 'mesh': 'D005047'}, {'text': 'myelosuppression', 'type': 'Disease', 'start': 318, 'end': 334, 'mesh': 'D001855'}, {'text': 'cardiac toxicity', 'type': 'Disease', 'start': 339, 'end': 355, 'mesh': 'D066126'}, {'text': 'Dexrazoxane', 'type': 'Chemical', 'start': 373, 'end': 384, 'mesh': 'D064730'}, {'text': 'ICRF-187', 'type': 'Chemical', 'start': 386, 'end': 394, 'mesh': 'D064730'}, {'text': 'anthracycline', 'type': 'Chemical', 'start': 434, 'end': 447, 'mesh': 'D018943'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 456, 'end': 470, 'mesh': 'D066126'}, {'text': 'hematologic toxicity', 'type': 'Disease', 'start': 530, 'end': 550, 'mesh': 'D006402'}, {'text': 'dexrazoxane', 'type': 'Chemical', 'start': 581, 'end': 592, 'mesh': 'D064730'}, {'text': 'etoposide', 'type': 'Chemical', 'start': 731, 'end': 740, 'mesh': 'D005047'}, {'text': 'daunorubicin', 'type': 'Chemical', 'start': 742, 'end': 754, 'mesh': 'D003630'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 760, 'end': 771, 'mesh': 'D004317'}, {'text': 'dexrazoxane', 'type': 'Chemical', 'start': 776, 'end': 787, 'mesh': 'D064730'}, {'text': 'etoposide', 'type': 'Chemical', 'start': 901, 'end': 910, 'mesh': 'D005047'}, {'text': 'daunorubicin', 'type': 'Chemical', 'start': 912, 'end': 924, 'mesh': 'D003630'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 930, 'end': 941, 'mesh': 'D004317'}, {'text': 'dexrazoxane', 'type': 'Chemical', 'start': 959, 'end': 970, 'mesh': 'D064730'}, {'text': 'dexrazoxane', 'type': 'Chemical', 'start': 1081, 'end': 1092, 'mesh': 'D064730'}, {'text': 'myelosuppression', 'type': 'Disease', 'start': 1101, 'end': 1117, 'mesh': 'D001855'}, {'text': 'weight loss', 'type': 'Disease', 'start': 1122, 'end': 1133, 'mesh': 'D015431'}, {'text': 'daunorubicin', 'type': 'Chemical', 'start': 1139, 'end': 1151, 'mesh': 'D003630'}, {'text': 'etoposide', 'type': 'Chemical', 'start': 1156, 'end': 1165, 'mesh': 'D005047'}, {'text': 'dexrazoxane', 'type': 'Chemical', 'start': 1252, 'end': 1263, 'mesh': 'D064730'}, {'text': 'myelosuppression', 'type': 'Disease', 'start': 1280, 'end': 1296, 'mesh': 'D001855'}, {'text': 'weight loss', 'type': 'Disease', 'start': 1298, 'end': 1309, 'mesh': 'D015431'}, {'text': 'cytotoxicity', 'type': 'Disease', 'start': 1328, 'end': 1340, 'mesh': 'D064420'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1346, 'end': 1357, 'mesh': 'D004317'}, {'text': 'dexrazoxane', 'type': 'Chemical', 'start': 1422, 'end': 1433, 'mesh': 'D064730'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1499, 'end': 1510, 'mesh': 'D004317'}, {'text': 'daunorubicin', 'type': 'Chemical', 'start': 1548, 'end': 1560, 'mesh': 'D003630'}, {'text': 'etoposide', 'type': 'Chemical', 'start': 1718, 'end': 1727, 'mesh': 'D005047'}, {'text': 'dexrazoxane', 'type': 'Chemical', 'start': 1778, 'end': 1789, 'mesh': 'D064730'}, {'text': 'metastases', 'type': 'Disease', 'start': 1830, 'end': 1840, 'mesh': 'D009362'}, {'text': 'dexrazoxane', 'type': 'Chemical', 'start': 1851, 'end': 1862, 'mesh': 'D064730'}, {'text': 'etoposide', 'type': 'Chemical', 'start': 1881, 'end': 1890, 'mesh': 'D005047'}, {'text': 'hematologic toxicity', 'type': 'Disease', 'start': 1957, 'end': 1977, 'mesh': 'D006402'}]"
+916,6817363,Effects of the novel compound aniracetam (Ro 13-5057) upon impaired learning and memory in rodents.,"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.","[{'text': 'aniracetam', 'type': 'Chemical', 'start': 30, 'end': 40, 'mesh': 'C036466'}, {'text': 'Ro 13-5057', 'type': 'Chemical', 'start': 42, 'end': 52, 'mesh': 'C036466'}, {'text': 'aniracetam', 'type': 'Chemical', 'start': 114, 'end': 124, 'mesh': 'C036466'}, {'text': 'Ro 13-5057', 'type': 'Chemical', 'start': 126, 'end': 136, 'mesh': 'C036466'}, {'text': '1-anisoyl-2-pyrrolidinone', 'type': 'Chemical', 'start': 138, 'end': 163, 'mesh': 'C036466'}, {'text': 'impaired cognitive functions', 'type': 'Disease', 'start': 212, 'end': 240, 'mesh': 'D003072'}, {'text': 'hypercapnia', 'type': 'Disease', 'start': 424, 'end': 435, 'mesh': 'D006935'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 536, 'end': 547, 'mesh': 'D012601'}, {'text': 'amnesia', 'type': 'Disease', 'start': 567, 'end': 574, 'mesh': 'D000647'}, {'text': 'amnesia', 'type': 'Disease', 'start': 637, 'end': 644, 'mesh': 'D000647'}, {'text': 'chloramphenicol', 'type': 'Chemical', 'start': 881, 'end': 896, 'mesh': 'D002701'}, {'text': 'cycloheximide', 'type': 'Chemical', 'start': 900, 'end': 913, 'mesh': 'D003513'}, {'text': 'cycloheximide', 'type': 'Chemical', 'start': 1112, 'end': 1125, 'mesh': 'D003513'}, {'text': 'hypercapnia', 'type': 'Disease', 'start': 1278, 'end': 1289, 'mesh': 'D006935'}, {'text': 'impaired cognitive functions', 'type': 'Disease', 'start': 1401, 'end': 1429, 'mesh': 'D003072'}, {'text': 'aniracetam', 'type': 'Chemical', 'start': 1448, 'end': 1458, 'mesh': 'C036466'}, {'text': 'aniracetam', 'type': 'Chemical', 'start': 1578, 'end': 1588, 'mesh': 'C036466'}, {'text': 'Piracetam', 'type': 'Chemical', 'start': 1631, 'end': 1640, 'mesh': 'D010889'}, {'text': 'pyrrolidinone', 'type': 'Chemical', 'start': 1650, 'end': 1663, 'mesh': 'D011760'}, {'text': 'aniracetam', 'type': 'Chemical', 'start': 1779, 'end': 1789, 'mesh': 'C036466'}, {'text': 'aniracetam', 'type': 'Chemical', 'start': 1817, 'end': 1827, 'mesh': 'C036466'}]"
+917,11900788,Nicotine potentiation of morphine-induced catalepsy in mice.,"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.","[{'text': 'Nicotine', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D009538'}, {'text': 'morphine', 'type': 'Chemical', 'start': 25, 'end': 33, 'mesh': 'D009020'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 42, 'end': 51, 'mesh': 'D002375'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 94, 'end': 102, 'mesh': 'D009538'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 106, 'end': 115, 'mesh': 'D002375'}, {'text': 'morphine', 'type': 'Chemical', 'start': 127, 'end': 135, 'mesh': 'D009020'}, {'text': 'Morphine', 'type': 'Chemical', 'start': 168, 'end': 176, 'mesh': 'D009020'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 185, 'end': 193, 'mesh': 'D009538'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 219, 'end': 228, 'mesh': 'D002375'}, {'text': 'morphine', 'type': 'Chemical', 'start': 246, 'end': 254, 'mesh': 'D009020'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 274, 'end': 282, 'mesh': 'D009538'}, {'text': 'atropine', 'type': 'Chemical', 'start': 318, 'end': 326, 'mesh': 'D001285'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 328, 'end': 336, 'mesh': 'D009270'}, {'text': 'mecamylamine', 'type': 'Chemical', 'start': 338, 'end': 350, 'mesh': 'D008464'}, {'text': 'hexamethonium', 'type': 'Chemical', 'start': 356, 'end': 369, 'mesh': 'D018738'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 386, 'end': 395, 'mesh': 'D002375'}, {'text': 'morphine', 'type': 'Chemical', 'start': 424, 'end': 432, 'mesh': 'D009020'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 438, 'end': 446, 'mesh': 'D009538'}, {'text': 'atropine', 'type': 'Chemical', 'start': 485, 'end': 493, 'mesh': 'D001285'}, {'text': 'hexamethonium', 'type': 'Chemical', 'start': 495, 'end': 508, 'mesh': 'D018738'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 514, 'end': 522, 'mesh': 'D009270'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 538, 'end': 547, 'mesh': 'D002375'}, {'text': 'morphine', 'type': 'Chemical', 'start': 559, 'end': 567, 'mesh': 'D009020'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 573, 'end': 581, 'mesh': 'D009538'}, {'text': 'atropine', 'type': 'Chemical', 'start': 617, 'end': 625, 'mesh': 'D001285'}, {'text': 'hexamethonium', 'type': 'Chemical', 'start': 691, 'end': 704, 'mesh': 'D018738'}, {'text': 'morphine', 'type': 'Chemical', 'start': 747, 'end': 755, 'mesh': 'D009020'}, {'text': 'morphine', 'type': 'Chemical', 'start': 779, 'end': 787, 'mesh': 'D009020'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 788, 'end': 797, 'mesh': 'D002375'}, {'text': 'morphine', 'type': 'Chemical', 'start': 875, 'end': 883, 'mesh': 'D009020'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 895, 'end': 903, 'mesh': 'D009538'}]"
+918,11230490,"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.","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.","[{'text': 'cardiotoxicity', 'type': 'Disease', 'start': 8, 'end': 22, 'mesh': 'D066126'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 81, 'end': 92, 'mesh': 'D004317'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 97, 'end': 113, 'mesh': 'D003520'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 141, 'end': 152, 'mesh': 'D004317'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 157, 'end': 173, 'mesh': 'D003520'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 223, 'end': 236, 'mesh': 'D001943'}, {'text': 'Myocet', 'type': 'Chemical', 'start': 268, 'end': 274, 'mesh': 'D004317'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 298, 'end': 309, 'mesh': 'D004317'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 386, 'end': 402, 'mesh': 'D003520'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 425, 'end': 436, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 437, 'end': 451, 'mesh': 'D066126'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 536, 'end': 549, 'mesh': 'D001943'}, {'text': 'MBC', 'type': 'Disease', 'start': 551, 'end': 554, 'mesh': 'D001943'}, {'text': 'MBC', 'type': 'Disease', 'start': 618, 'end': 621, 'mesh': 'D001943'}, {'text': 'Myocet', 'type': 'Chemical', 'start': 719, 'end': 725, 'mesh': 'D004317'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 746, 'end': 757, 'mesh': 'D004317'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 798, 'end': 814, 'mesh': 'D003520'}, {'text': 'toxicity', 'type': 'Disease', 'start': 876, 'end': 884, 'mesh': 'D064420'}, {'text': 'Cardiotoxicity', 'type': 'Disease', 'start': 886, 'end': 900, 'mesh': 'D066126'}, {'text': 'congestive heart failure', 'type': 'Disease', 'start': 1031, 'end': 1055, 'mesh': 'D006333'}, {'text': 'CHF', 'type': 'Disease', 'start': 1057, 'end': 1060, 'mesh': 'D006333'}, {'text': 'tumor', 'type': 'Disease', 'start': 1108, 'end': 1113, 'mesh': 'D009369'}, {'text': 'CHF', 'type': 'Disease', 'start': 1274, 'end': 1277, 'mesh': 'D006333'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1304, 'end': 1318, 'mesh': 'D066126'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1349, 'end': 1360, 'mesh': 'D004317'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 1510, 'end': 1521, 'mesh': 'D009503'}, {'text': 'Myocet', 'type': 'Chemical', 'start': 1779, 'end': 1785, 'mesh': 'D004317'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1820, 'end': 1831, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1858, 'end': 1872, 'mesh': 'D066126'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 1885, 'end': 1896, 'mesh': 'D009503'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 1971, 'end': 1987, 'mesh': 'D003520'}, {'text': 'MBC', 'type': 'Disease', 'start': 2014, 'end': 2017, 'mesh': 'D001943'}]"
+919,2594614,"Protective effect of a specific platelet-activating factor antagonist, BN 52021, on bupivacaine-induced cardiovascular impairments in rats.","Administration of the local anaesthetic bupivacaine (1.5 or 2 mg/kg, i.v.) to rats elicited a marked decrease of mean arterial blood pressure (MBP) and heart rate (HR) leading to death (in 67% or 90% of animals respectively). Intravenous injection of the specific platelet-activating factor (PAF) antagonist BN 52021 (10 mg/kg), 30 min before bupivacaine administration (2 mg/kg i.v.) suppressed both the decrease of MBP and HR. In contrast, doses of 1 mg/kg BN 52021 given 30 min before or 10 mg/kg administered 5 min before i.v. injection of bupivacaine were ineffective. 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. Thus, consistent with its direct effect on heart, PAF appears to be implicated in bupivacaine-induced cardiovascular alterations.","[{'text': 'BN 52021', 'type': 'Chemical', 'start': 71, 'end': 79, 'mesh': 'C045856'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 84, 'end': 95, 'mesh': 'D002045'}, {'text': 'cardiovascular impairments', 'type': 'Disease', 'start': 104, 'end': 130, 'mesh': 'D002318'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 180, 'end': 191, 'mesh': 'D002045'}, {'text': 'BN 52021', 'type': 'Chemical', 'start': 448, 'end': 456, 'mesh': 'C045856'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 483, 'end': 494, 'mesh': 'D002045'}, {'text': 'BN 52021', 'type': 'Chemical', 'start': 599, 'end': 607, 'mesh': 'C045856'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 684, 'end': 695, 'mesh': 'D002045'}, {'text': 'BN 52021', 'type': 'Chemical', 'start': 719, 'end': 727, 'mesh': 'C045856'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 775, 'end': 786, 'mesh': 'D002045'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 930, 'end': 941, 'mesh': 'D002045'}, {'text': 'BN 52021', 'type': 'Chemical', 'start': 1015, 'end': 1023, 'mesh': 'C045856'}, {'text': 'BN 52021', 'type': 'Chemical', 'start': 1053, 'end': 1061, 'mesh': 'C045856'}, {'text': 'BN 52021', 'type': 'Chemical', 'start': 1198, 'end': 1206, 'mesh': 'C045856'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 1246, 'end': 1257, 'mesh': 'D002045'}, {'text': 'cardiovascular toxicity', 'type': 'Disease', 'start': 1266, 'end': 1289, 'mesh': 'D002318'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 1373, 'end': 1384, 'mesh': 'D002045'}, {'text': 'cardiovascular alterations', 'type': 'Disease', 'start': 1393, 'end': 1419, 'mesh': 'D018376'}]"
+920,2257294,Benzylacyclouridine reverses azidothymidine-induced marrow suppression without impairment of anti-human immunodeficiency virus activity.,"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.","[{'text': 'Benzylacyclouridine', 'type': 'Chemical', 'start': 0, 'end': 19, 'mesh': 'C034753'}, {'text': 'azidothymidine', 'type': 'Chemical', 'start': 29, 'end': 43, 'mesh': 'D015215'}, {'text': 'marrow suppression', 'type': 'Disease', 'start': 52, 'end': 70, 'mesh': 'D001855'}, {'text': 'immunodeficiency', 'type': 'Disease', 'start': 104, 'end': 120, 'mesh': 'D007153'}, {'text': 'uridine', 'type': 'Chemical', 'start': 179, 'end': 186, 'mesh': 'D014529'}, {'text': 'Urd', 'type': 'Chemical', 'start': 188, 'end': 191, 'mesh': 'D014529'}, {'text': 'azidothymidine', 'type': 'Chemical', 'start': 233, 'end': 247, 'mesh': 'D015215'}, {'text': 'AZT', 'type': 'Chemical', 'start': 249, 'end': 252, 'mesh': 'D015215'}, {'text': 'immunodeficiency', 'type': 'Disease', 'start': 358, 'end': 374, 'mesh': 'D007153'}, {'text': 'toxicities', 'type': 'Disease', 'start': 421, 'end': 431, 'mesh': 'D064420'}, {'text': 'Urd', 'type': 'Chemical', 'start': 456, 'end': 459, 'mesh': 'D014529'}, {'text': 'benzylacyclouridine', 'type': 'Chemical', 'start': 491, 'end': 510, 'mesh': 'C034753'}, {'text': 'BAU', 'type': 'Chemical', 'start': 512, 'end': 515, 'mesh': 'C034753'}, {'text': 'AZT', 'type': 'Chemical', 'start': 537, 'end': 540, 'mesh': 'D015215'}, {'text': 'anemia', 'type': 'Disease', 'start': 549, 'end': 555, 'mesh': 'D000740'}, {'text': 'leukopenia', 'type': 'Disease', 'start': 560, 'end': 570, 'mesh': 'D007970'}, {'text': 'Urd', 'type': 'Chemical', 'start': 605, 'end': 608, 'mesh': 'D014529'}, {'text': 'Urd', 'type': 'Chemical', 'start': 672, 'end': 675, 'mesh': 'D014529'}, {'text': 'Urd', 'type': 'Chemical', 'start': 712, 'end': 715, 'mesh': 'D014529'}, {'text': 'toxicity', 'type': 'Disease', 'start': 724, 'end': 732, 'mesh': 'D064420'}, {'text': 'anemic', 'type': 'Disease', 'start': 751, 'end': 757, 'mesh': 'D000740'}, {'text': 'leukopenic', 'type': 'Disease', 'start': 762, 'end': 772, 'mesh': 'D007970'}, {'text': 'AZT', 'type': 'Chemical', 'start': 798, 'end': 801, 'mesh': 'D015215'}, {'text': 'AZT', 'type': 'Chemical', 'start': 877, 'end': 880, 'mesh': 'D015215'}, {'text': 'BAU', 'type': 'Chemical', 'start': 892, 'end': 895, 'mesh': 'C034753'}, {'text': 'AZT', 'type': 'Chemical', 'start': 935, 'end': 938, 'mesh': 'D015215'}, {'text': 'anemia', 'type': 'Disease', 'start': 947, 'end': 953, 'mesh': 'D000740'}, {'text': 'leukopenia', 'type': 'Disease', 'start': 958, 'end': 968, 'mesh': 'D007970'}, {'text': 'megaloblastosis', 'type': 'Disease', 'start': 1101, 'end': 1116, 'mesh': '-1'}, {'text': 'AZT', 'type': 'Chemical', 'start': 1143, 'end': 1146, 'mesh': 'D015215'}, {'text': 'BAU', 'type': 'Chemical', 'start': 1186, 'end': 1189, 'mesh': 'C034753'}, {'text': 'AZT', 'type': 'Chemical', 'start': 1198, 'end': 1201, 'mesh': 'D015215'}, {'text': 'marrow toxicity', 'type': 'Disease', 'start': 1210, 'end': 1225, 'mesh': 'D001855'}, {'text': 'BAU', 'type': 'Chemical', 'start': 1272, 'end': 1275, 'mesh': 'C034753'}, {'text': 'AZT', 'type': 'Chemical', 'start': 1348, 'end': 1351, 'mesh': 'D015215'}]"
+921,10840460,Cyclophosphamide-induced cystitis in freely-moving conscious rats: behavioral approach to a new model of visceral pain.,"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.","[{'text': 'Cyclophosphamide', 'type': 'Chemical', 'start': 0, 'end': 16, 'mesh': 'D003520'}, {'text': 'cystitis', 'type': 'Disease', 'start': 25, 'end': 33, 'mesh': 'D003556'}, {'text': 'visceral pain', 'type': 'Disease', 'start': 105, 'end': 118, 'mesh': 'D059265'}, {'text': 'visceral pain', 'type': 'Disease', 'start': 151, 'end': 164, 'mesh': 'D059265'}, {'text': 'Cyclophosphamide', 'type': 'Chemical', 'start': 202, 'end': 218, 'mesh': 'D003520'}, {'text': 'CP', 'type': 'Chemical', 'start': 220, 'end': 222, 'mesh': 'D003520'}, {'text': 'acrolein', 'type': 'Chemical', 'start': 331, 'end': 339, 'mesh': 'D000171'}, {'text': 'cystitis', 'type': 'Disease', 'start': 360, 'end': 368, 'mesh': 'D003556'}, {'text': 'CP', 'type': 'Chemical', 'start': 393, 'end': 395, 'mesh': 'D003520'}, {'text': 'morphine', 'type': 'Chemical', 'start': 523, 'end': 531, 'mesh': 'D009020'}, {'text': 'CP', 'type': 'Chemical', 'start': 559, 'end': 561, 'mesh': 'D003520'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 636, 'end': 644, 'mesh': 'D009270'}, {'text': 'CP', 'type': 'Chemical', 'start': 693, 'end': 695, 'mesh': 'D003520'}, {'text': 'morphine', 'type': 'Chemical', 'start': 749, 'end': 757, 'mesh': 'D009020'}, {'text': 'CP', 'type': 'Chemical', 'start': 881, 'end': 883, 'mesh': 'D003520'}, {'text': 'CP', 'type': 'Chemical', 'start': 944, 'end': 946, 'mesh': 'D003520'}, {'text': 'acrolein', 'type': 'Chemical', 'start': 1021, 'end': 1029, 'mesh': 'D000171'}, {'text': 'CP', 'type': 'Chemical', 'start': 1107, 'end': 1109, 'mesh': 'D003520'}, {'text': 'Morphine', 'type': 'Chemical', 'start': 1261, 'end': 1269, 'mesh': 'D009020'}, {'text': 'behavioral disorders', 'type': 'Disease', 'start': 1302, 'end': 1322, 'mesh': 'D001523'}, {'text': 'CP', 'type': 'Chemical', 'start': 1416, 'end': 1418, 'mesh': 'D003520'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 1489, 'end': 1497, 'mesh': 'D009270'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1532, 'end': 1540, 'mesh': 'D009020'}, {'text': 'edema', 'type': 'Disease', 'start': 1625, 'end': 1630, 'mesh': 'D004487'}, {'text': 'CP', 'type': 'Chemical', 'start': 1663, 'end': 1665, 'mesh': 'D003520'}, {'text': 'CP', 'type': 'Chemical', 'start': 1816, 'end': 1818, 'mesh': 'D003520'}, {'text': 'acrolein', 'type': 'Chemical', 'start': 1867, 'end': 1875, 'mesh': 'D000171'}, {'text': 'CP', 'type': 'Chemical', 'start': 1960, 'end': 1962, 'mesh': 'D003520'}, {'text': 'acrolein', 'type': 'Chemical', 'start': 2023, 'end': 2031, 'mesh': 'D000171'}, {'text': 'CP', 'type': 'Chemical', 'start': 2171, 'end': 2173, 'mesh': 'D003520'}, {'text': 'cystitis', 'type': 'Disease', 'start': 2182, 'end': 2190, 'mesh': 'D003556'}, {'text': 'visceral pain', 'type': 'Disease', 'start': 2250, 'end': 2263, 'mesh': 'D059265'}, {'text': 'painful syndromes', 'type': 'Disease', 'start': 2306, 'end': 2323, 'mesh': 'D010146'}]"
+922,8278214,Hyperalgesia and myoclonus in terminal cancer patients treated with continuous intravenous morphine.,"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.","[{'text': 'Hyperalgesia', 'type': 'Disease', 'start': 0, 'end': 12, 'mesh': 'D006930'}, {'text': 'myoclonus', 'type': 'Disease', 'start': 17, 'end': 26, 'mesh': 'D009207'}, {'text': 'cancer', 'type': 'Disease', 'start': 39, 'end': 45, 'mesh': 'D009369'}, {'text': 'morphine', 'type': 'Chemical', 'start': 91, 'end': 99, 'mesh': 'D009020'}, {'text': 'cancer', 'type': 'Disease', 'start': 107, 'end': 113, 'mesh': 'D009369'}, {'text': 'morphine', 'type': 'Chemical', 'start': 200, 'end': 208, 'mesh': 'D009020'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 219, 'end': 231, 'mesh': 'D006930'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 352, 'end': 364, 'mesh': 'D006930'}, {'text': 'hyperesthesia', 'type': 'Disease', 'start': 369, 'end': 382, 'mesh': 'D006941'}, {'text': 'myoclonus', 'type': 'Disease', 'start': 420, 'end': 429, 'mesh': 'D009207'}, {'text': 'neuralgia', 'type': 'Disease', 'start': 460, 'end': 469, 'mesh': 'D009437'}, {'text': 'myoclonus', 'type': 'Disease', 'start': 530, 'end': 539, 'mesh': 'D009207'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 633, 'end': 645, 'mesh': 'D006930'}, {'text': 'myoclonus', 'type': 'Disease', 'start': 646, 'end': 655, 'mesh': 'D009207'}, {'text': 'morphine', 'type': 'Chemical', 'start': 674, 'end': 682, 'mesh': 'D009020'}, {'text': 'morphine', 'type': 'Chemical', 'start': 754, 'end': 762, 'mesh': 'D009020'}]"
+923,3934126,A prospective study of adverse reactions associated with vancomycin therapy.,"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.","[{'text': 'vancomycin', 'type': 'Chemical', 'start': 57, 'end': 67, 'mesh': 'D014640'}, {'text': 'vancomycin', 'type': 'Chemical', 'start': 132, 'end': 142, 'mesh': 'D014640'}, {'text': 'Vancomycin', 'type': 'Chemical', 'start': 208, 'end': 218, 'mesh': 'D014640'}, {'text': 'infection', 'type': 'Disease', 'start': 266, 'end': 275, 'mesh': 'D007239'}, {'text': 'vancomycin', 'type': 'Chemical', 'start': 359, 'end': 369, 'mesh': 'D014640'}, {'text': 'thrombophlebitis', 'type': 'Disease', 'start': 422, 'end': 438, 'mesh': 'D013924'}, {'text': 'rash', 'type': 'Disease', 'start': 460, 'end': 464, 'mesh': 'D005076'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 476, 'end': 490, 'mesh': 'D007674'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 502, 'end': 513, 'mesh': 'D011507'}, {'text': 'ototoxicity', 'type': 'Disease', 'start': 528, 'end': 539, 'mesh': 'D006311'}, {'text': 'Thrombophlebitis', 'type': 'Disease', 'start': 581, 'end': 597, 'mesh': 'D013924'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 655, 'end': 669, 'mesh': 'D007674'}, {'text': 'ototoxicity', 'type': 'Disease', 'start': 674, 'end': 685, 'mesh': 'D006311'}, {'text': 'aminoglycoside', 'type': 'Chemical', 'start': 725, 'end': 739, 'mesh': 'D000617'}, {'text': 'vancomycin', 'type': 'Chemical', 'start': 745, 'end': 755, 'mesh': 'D014640'}, {'text': 'vancomycin', 'type': 'Chemical', 'start': 774, 'end': 784, 'mesh': 'D014640'}, {'text': 'infections', 'type': 'Disease', 'start': 854, 'end': 864, 'mesh': 'D007239'}]"
+924,1687392,Blockade of both D-1 and D-2 dopamine receptors may induce catalepsy in mice.,"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.","[{'text': 'dopamine', 'type': 'Chemical', 'start': 29, 'end': 37, 'mesh': 'D004298'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 59, 'end': 68, 'mesh': 'D002375'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 85, 'end': 94, 'mesh': 'D002375'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 106, 'end': 114, 'mesh': 'D004298'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 160, 'end': 168, 'mesh': 'D004298'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 190, 'end': 199, 'mesh': 'D002375'}, {'text': 'Dopamine', 'type': 'Chemical', 'start': 219, 'end': 227, 'mesh': 'D004298'}, {'text': 'fluphenazine', 'type': 'Chemical', 'start': 239, 'end': 251, 'mesh': 'D005476'}, {'text': 'SCH 23390', 'type': 'Chemical', 'start': 268, 'end': 277, 'mesh': 'C534628'}, {'text': 'sulpiride', 'type': 'Chemical', 'start': 296, 'end': 305, 'mesh': 'D013469'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 314, 'end': 323, 'mesh': 'D002375'}, {'text': 'fluphenazine', 'type': 'Chemical', 'start': 339, 'end': 351, 'mesh': 'D005476'}, {'text': 'sulpiride', 'type': 'Chemical', 'start': 356, 'end': 365, 'mesh': 'D013469'}, {'text': 'SCH 23390', 'type': 'Chemical', 'start': 401, 'end': 410, 'mesh': 'C534628'}, {'text': 'sulpiride', 'type': 'Chemical', 'start': 416, 'end': 425, 'mesh': 'D013469'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 441, 'end': 450, 'mesh': 'D002375'}, {'text': 'SKF 38393', 'type': 'Chemical', 'start': 480, 'end': 489, 'mesh': 'D015647'}, {'text': 'quinpirole', 'type': 'Chemical', 'start': 505, 'end': 515, 'mesh': 'D019257'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 530, 'end': 539, 'mesh': 'D002375'}, {'text': 'fluphenazine', 'type': 'Chemical', 'start': 551, 'end': 563, 'mesh': 'D005476'}, {'text': 'SCH 23390', 'type': 'Chemical', 'start': 565, 'end': 574, 'mesh': 'C534628'}, {'text': 'sulpiride', 'type': 'Chemical', 'start': 578, 'end': 587, 'mesh': 'D013469'}, {'text': 'SKF 38393', 'type': 'Chemical', 'start': 607, 'end': 616, 'mesh': 'D015647'}, {'text': 'quinpirole', 'type': 'Chemical', 'start': 622, 'end': 632, 'mesh': 'D019257'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 680, 'end': 689, 'mesh': 'D002375'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 701, 'end': 709, 'mesh': 'D004298'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 799, 'end': 808, 'mesh': 'D002375'}]"
+925,19719056,"Dextran-etodolac conjugates: synthesis, in vitro and in vivo evaluation.","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.","[{'text': 'Dextran', 'type': 'Chemical', 'start': 0, 'end': 7, 'mesh': 'D003911'}, {'text': 'etodolac', 'type': 'Chemical', 'start': 8, 'end': 16, 'mesh': 'D017308'}, {'text': 'Etodolac', 'type': 'Chemical', 'start': 73, 'end': 81, 'mesh': 'D017308'}, {'text': 'E', 'type': 'Chemical', 'start': 83, 'end': 84, 'mesh': 'D017308'}, {'text': 'dextran', 'type': 'Chemical', 'start': 166, 'end': 173, 'mesh': 'D003911'}, {'text': 'etodolac', 'type': 'Chemical', 'start': 222, 'end': 230, 'mesh': 'D017308'}, {'text': 'dextran', 'type': 'Chemical', 'start': 231, 'end': 238, 'mesh': 'D003911'}, {'text': 'N-acylimidazole', 'type': 'Chemical', 'start': 357, 'end': 372, 'mesh': '-1'}, {'text': 'etodolac', 'type': 'Chemical', 'start': 387, 'end': 395, 'mesh': 'D017308'}, {'text': 'EAI', 'type': 'Chemical', 'start': 397, 'end': 400, 'mesh': '-1'}, {'text': 'dextran', 'type': 'Chemical', 'start': 449, 'end': 456, 'mesh': 'D003911'}, {'text': 'Etodolac', 'type': 'Chemical', 'start': 596, 'end': 604, 'mesh': 'D017308'}, {'text': 'etodolac', 'type': 'Chemical', 'start': 903, 'end': 911, 'mesh': 'D017308'}, {'text': 'acetic acid', 'type': 'Chemical', 'start': 1165, 'end': 1176, 'mesh': 'D019342'}, {'text': 'writhing', 'type': 'Disease', 'start': 1185, 'end': 1193, 'mesh': 'D010146'}, {'text': 'carrageenan', 'type': 'Chemical', 'start': 1211, 'end': 1222, 'mesh': 'D002351'}, {'text': 'edema', 'type': 'Disease', 'start': 1239, 'end': 1244, 'mesh': 'D004487'}, {'text': 'E', 'type': 'Chemical', 'start': 1292, 'end': 1293, 'mesh': 'D017308'}, {'text': 'etodolac', 'type': 'Chemical', 'start': 1579, 'end': 1587, 'mesh': 'D017308'}]"
+926,15266362,Hypersensitivity myocarditis complicating hypertrophic cardiomyopathy heart.,"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.","[{'text': 'Hypersensitivity', 'type': 'Disease', 'start': 0, 'end': 16, 'mesh': 'D004342'}, {'text': 'myocarditis', 'type': 'Disease', 'start': 17, 'end': 28, 'mesh': 'D009205'}, {'text': 'hypertrophic cardiomyopathy', 'type': 'Disease', 'start': 42, 'end': 69, 'mesh': 'D002312'}, {'text': 'hypertrophic cardiomyopathy', 'type': 'Disease', 'start': 154, 'end': 181, 'mesh': 'D002312'}, {'text': 'hypertrophic cardiomyopathy', 'type': 'Disease', 'start': 229, 'end': 256, 'mesh': 'D002312'}, {'text': 'biventricular failure', 'type': 'Disease', 'start': 276, 'end': 297, 'mesh': 'D018754'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 328, 'end': 338, 'mesh': 'D004280'}, {'text': 'left ventricular dysfunction', 'type': 'Disease', 'start': 462, 'end': 490, 'mesh': 'D018487'}, {'text': 'mitral regurgitation', 'type': 'Disease', 'start': 530, 'end': 550, 'mesh': 'D008944'}, {'text': 'hypertrophic cardiomyopathy', 'type': 'Disease', 'start': 604, 'end': 631, 'mesh': 'D002312'}, {'text': 'myocarditis', 'type': 'Disease', 'start': 636, 'end': 647, 'mesh': 'D009205'}, {'text': 'Myocarditis', 'type': 'Disease', 'start': 675, 'end': 686, 'mesh': 'D009205'}, {'text': 'hypersensitivity', 'type': 'Disease', 'start': 756, 'end': 772, 'mesh': 'D004342'}, {'text': 'eosinophilic', 'type': 'Disease', 'start': 774, 'end': 786, 'mesh': 'D004802'}, {'text': 'myocarditis', 'type': 'Disease', 'start': 788, 'end': 799, 'mesh': 'D009205'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 815, 'end': 825, 'mesh': 'D004280'}]"
+927,14648024,All- trans-retinoic acid-induced erythema nodosum in patients with acute promyelocytic leukemia.,"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.","[{'text': 'All- trans-retinoic acid', 'type': 'Chemical', 'start': 0, 'end': 24, 'mesh': 'D014212'}, {'text': 'erythema nodosum', 'type': 'Disease', 'start': 33, 'end': 49, 'mesh': 'D004893'}, {'text': 'acute promyelocytic leukemia', 'type': 'Disease', 'start': 67, 'end': 95, 'mesh': 'D015473'}, {'text': 'Erythema nodosum', 'type': 'Disease', 'start': 97, 'end': 113, 'mesh': 'D004893'}, {'text': 'all- trans-retinoic acid', 'type': 'Chemical', 'start': 130, 'end': 154, 'mesh': 'D014212'}, {'text': 'ATRA', 'type': 'Chemical', 'start': 156, 'end': 160, 'mesh': 'D014212'}, {'text': 'acute promyelocytic leukemia', 'type': 'Disease', 'start': 166, 'end': 194, 'mesh': 'D015473'}, {'text': 'APL', 'type': 'Disease', 'start': 196, 'end': 199, 'mesh': 'D015473'}, {'text': 'APL', 'type': 'Disease', 'start': 254, 'end': 257, 'mesh': 'D015473'}, {'text': 'erythema nodosum', 'type': 'Disease', 'start': 272, 'end': 288, 'mesh': 'D004893'}, {'text': 'ATRA', 'type': 'Chemical', 'start': 296, 'end': 300, 'mesh': 'D014212'}, {'text': 'Fever', 'type': 'Disease', 'start': 310, 'end': 315, 'mesh': 'D005334'}, {'text': 'painful', 'type': 'Disease', 'start': 340, 'end': 347, 'mesh': 'D010146'}, {'text': 'erythematous nodules', 'type': 'Disease', 'start': 348, 'end': 368, 'mesh': 'D004893'}, {'text': 'ATRA', 'type': 'Chemical', 'start': 443, 'end': 447, 'mesh': 'D014212'}, {'text': 'erythema nodosum', 'type': 'Disease', 'start': 517, 'end': 533, 'mesh': 'D004893'}, {'text': 'steroids', 'type': 'Chemical', 'start': 573, 'end': 581, 'mesh': 'D013256'}, {'text': 'Fever', 'type': 'Disease', 'start': 583, 'end': 588, 'mesh': 'D005334'}, {'text': 'ATRA', 'type': 'Chemical', 'start': 712, 'end': 716, 'mesh': 'D014212'}, {'text': 'ATRA', 'type': 'Chemical', 'start': 718, 'end': 722, 'mesh': 'D014212'}, {'text': 'erythema nodosum', 'type': 'Disease', 'start': 766, 'end': 782, 'mesh': 'D004893'}, {'text': 'steroid', 'type': 'Chemical', 'start': 818, 'end': 825, 'mesh': 'D013256'}, {'text': 'ATRA', 'type': 'Chemical', 'start': 847, 'end': 851, 'mesh': 'D014212'}, {'text': 'erythema nodosum', 'type': 'Disease', 'start': 860, 'end': 876, 'mesh': 'D004893'}]"
+928,11827497,Delayed-onset heparin-induced thrombocytopenia.,"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.","[{'text': 'heparin', 'type': 'Chemical', 'start': 14, 'end': 21, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 30, 'end': 46, 'mesh': 'D013921'}, {'text': 'Heparin', 'type': 'Chemical', 'start': 60, 'end': 67, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 76, 'end': 92, 'mesh': 'D013921'}, {'text': 'heparin', 'type': 'Chemical', 'start': 121, 'end': 128, 'mesh': 'D006493'}, {'text': 'heparin', 'type': 'Chemical', 'start': 226, 'end': 233, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 242, 'end': 258, 'mesh': 'D013921'}, {'text': 'heparin', 'type': 'Chemical', 'start': 405, 'end': 412, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 421, 'end': 437, 'mesh': 'D013921'}, {'text': 'heparin', 'type': 'Chemical', 'start': 626, 'end': 633, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 642, 'end': 658, 'mesh': 'D013921'}, {'text': 'thromboembolic', 'type': 'Disease', 'start': 704, 'end': 718, 'mesh': 'D013923'}, {'text': 'thromboembolism', 'type': 'Disease', 'start': 797, 'end': 812, 'mesh': 'D013923'}, {'text': 'heparin', 'type': 'Chemical', 'start': 825, 'end': 832, 'mesh': 'D006493'}, {'text': 'heparin', 'type': 'Chemical', 'start': 958, 'end': 965, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 999, 'end': 1015, 'mesh': 'D013921'}, {'text': 'thromboembolic', 'type': 'Disease', 'start': 1081, 'end': 1095, 'mesh': 'D013923'}, {'text': 'Thromboemboli', 'type': 'Disease', 'start': 1111, 'end': 1124, 'mesh': 'D013923'}, {'text': 'pulmonary emboli', 'type': 'Disease', 'start': 1158, 'end': 1174, 'mesh': 'D011655'}, {'text': 'heparin', 'type': 'Chemical', 'start': 1343, 'end': 1350, 'mesh': 'D006493'}, {'text': 'heparin', 'type': 'Chemical', 'start': 1511, 'end': 1518, 'mesh': 'D006493'}, {'text': 'heparin', 'type': 'Chemical', 'start': 1584, 'end': 1591, 'mesh': 'D006493'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 1805, 'end': 1813, 'mesh': 'D014859'}, {'text': 'heparin', 'type': 'Chemical', 'start': 1877, 'end': 1884, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 1893, 'end': 1909, 'mesh': 'D013921'}, {'text': 'heparin', 'type': 'Chemical', 'start': 1999, 'end': 2006, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 2015, 'end': 2031, 'mesh': 'D013921'}, {'text': 'thromboembolism', 'type': 'Disease', 'start': 2086, 'end': 2101, 'mesh': 'D013923'}, {'text': 'heparin', 'type': 'Chemical', 'start': 2148, 'end': 2155, 'mesh': 'D006493'}]"
+929,8841157,"Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: a comparative study of the efficacy and safety against amlodipine.","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.","[{'text': 'Valsartan', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'C081489'}, {'text': 'angiotensin II', 'type': 'Chemical', 'start': 17, 'end': 31, 'mesh': 'D000804'}, {'text': 'hypertension', 'type': 'Disease', 'start': 74, 'end': 86, 'mesh': 'D006973'}, {'text': 'amlodipine', 'type': 'Chemical', 'start': 143, 'end': 153, 'mesh': 'D017311'}, {'text': 'angiotensin II', 'type': 'Chemical', 'start': 216, 'end': 230, 'mesh': 'D000804'}, {'text': 'valsartan', 'type': 'Chemical', 'start': 243, 'end': 252, 'mesh': 'C081489'}, {'text': 'amlodipine', 'type': 'Chemical', 'start': 280, 'end': 290, 'mesh': 'D017311'}, {'text': 'hypertension', 'type': 'Disease', 'start': 365, 'end': 377, 'mesh': 'D006973'}, {'text': 'valsartan', 'type': 'Chemical', 'start': 460, 'end': 469, 'mesh': 'C081489'}, {'text': 'amlodipine', 'type': 'Chemical', 'start': 478, 'end': 488, 'mesh': 'D017311'}, {'text': 'amlodipine', 'type': 'Chemical', 'start': 590, 'end': 600, 'mesh': 'D017311'}, {'text': 'valsartan', 'type': 'Chemical', 'start': 895, 'end': 904, 'mesh': 'C081489'}, {'text': 'amlodipine', 'type': 'Chemical', 'start': 909, 'end': 919, 'mesh': 'D017311'}, {'text': 'valsartan', 'type': 'Chemical', 'start': 1191, 'end': 1200, 'mesh': 'C081489'}, {'text': 'valsartan', 'type': 'Chemical', 'start': 1293, 'end': 1302, 'mesh': 'C081489'}, {'text': 'amlodipine', 'type': 'Chemical', 'start': 1317, 'end': 1327, 'mesh': 'D017311'}, {'text': 'edema', 'type': 'Disease', 'start': 1417, 'end': 1422, 'mesh': 'D004487'}, {'text': 'amlodipine', 'type': 'Chemical', 'start': 1450, 'end': 1460, 'mesh': 'D017311'}, {'text': 'valsartan', 'type': 'Chemical', 'start': 1524, 'end': 1533, 'mesh': 'C081489'}, {'text': 'amlodipine', 'type': 'Chemical', 'start': 1549, 'end': 1559, 'mesh': 'D017311'}, {'text': 'valsartan', 'type': 'Chemical', 'start': 1568, 'end': 1577, 'mesh': 'C081489'}, {'text': 'amlodipine', 'type': 'Chemical', 'start': 1588, 'end': 1598, 'mesh': 'D017311'}, {'text': 'amlodipine', 'type': 'Chemical', 'start': 1616, 'end': 1626, 'mesh': 'D017311'}, {'text': 'valsartan', 'type': 'Chemical', 'start': 1661, 'end': 1670, 'mesh': 'C081489'}, {'text': 'amlodipine', 'type': 'Chemical', 'start': 1699, 'end': 1709, 'mesh': 'D017311'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1747, 'end': 1759, 'mesh': 'D006973'}, {'text': 'valsartan', 'type': 'Chemical', 'start': 1783, 'end': 1792, 'mesh': 'C081489'}, {'text': 'dihydropyridine', 'type': 'Chemical', 'start': 1911, 'end': 1926, 'mesh': 'C038806'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1927, 'end': 1934, 'mesh': 'D002118'}]"
+930,8045270,KF17837: a novel selective adenosine A2A receptor antagonist with anticataleptic activity.,"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.","[{'text': 'KF17837', 'type': 'Chemical', 'start': 0, 'end': 7, 'mesh': 'C081198'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 27, 'end': 36, 'mesh': 'D000241'}, {'text': 'KF17837', 'type': 'Chemical', 'start': 91, 'end': 98, 'mesh': 'C081198'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 120, 'end': 129, 'mesh': 'D000241'}, {'text': 'KF17837', 'type': 'Chemical', 'start': 178, 'end': 185, 'mesh': 'C081198'}, {'text': 'cataleptic', 'type': 'Disease', 'start': 243, 'end': 253, 'mesh': 'D002375'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 320, 'end': 329, 'mesh': 'D000241'}, {'text': 'CGS 21680', 'type': 'Chemical', 'start': 352, 'end': 361, 'mesh': 'C061282'}, {'text': 'KF17837', 'type': 'Chemical', 'start': 407, 'end': 414, 'mesh': 'C081198'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 432, 'end': 441, 'mesh': 'D002375'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 453, 'end': 464, 'mesh': 'D006220'}, {'text': 'reserpine', 'type': 'Chemical', 'start': 487, 'end': 496, 'mesh': 'D012110'}, {'text': 'KF17837', 'type': 'Chemical', 'start': 638, 'end': 645, 'mesh': 'C081198'}, {'text': 'L-3,4-dihydroxyphenylalanine', 'type': 'Chemical', 'start': 730, 'end': 758, 'mesh': 'D007980'}, {'text': 'L-DOPA', 'type': 'Chemical', 'start': 760, 'end': 766, 'mesh': 'D007980'}, {'text': 'benserazide', 'type': 'Chemical', 'start': 788, 'end': 799, 'mesh': 'D001545'}, {'text': 'KF17837', 'type': 'Chemical', 'start': 848, 'end': 855, 'mesh': 'C081198'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 878, 'end': 887, 'mesh': 'D000241'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 994, 'end': 1003, 'mesh': 'D000241'}, {'text': 'KF17837', 'type': 'Chemical', 'start': 1043, 'end': 1050, 'mesh': 'C081198'}, {'text': 'parkinsonism', 'type': 'Disease', 'start': 1092, 'end': 1104, 'mesh': 'D010302'}]"
+931,2576810,Some central effects of repeated treatment with fluvoxamine.,"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.","[{'text': 'fluvoxamine', 'type': 'Chemical', 'start': 48, 'end': 59, 'mesh': 'D016666'}, {'text': 'fluvoxamine', 'type': 'Chemical', 'start': 115, 'end': 126, 'mesh': 'D016666'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 140, 'end': 149, 'mesh': 'D012701'}, {'text': 'methoxamine', 'type': 'Chemical', 'start': 214, 'end': 225, 'mesh': 'D008729'}, {'text': 'fluvoxamine', 'type': 'Chemical', 'start': 313, 'end': 324, 'mesh': 'D016666'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 396, 'end': 407, 'mesh': 'D000661'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 416, 'end': 429, 'mesh': 'D006948'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 435, 'end': 448, 'mesh': 'D006948'}, {'text': 'nomifensine', 'type': 'Chemical', 'start': 460, 'end': 471, 'mesh': 'D009627'}, {'text': 'fluvoxamine', 'type': 'Chemical', 'start': 503, 'end': 514, 'mesh': 'D016666'}, {'text': 'methoxamine', 'type': 'Chemical', 'start': 596, 'end': 607, 'mesh': 'D008729'}, {'text': 'fluvoxamine', 'type': 'Chemical', 'start': 652, 'end': 663, 'mesh': 'D016666'}, {'text': 'fluvoxamine', 'type': 'Chemical', 'start': 683, 'end': 694, 'mesh': 'D016666'}, {'text': 'fluvoxamine', 'type': 'Chemical', 'start': 804, 'end': 815, 'mesh': 'D016666'}, {'text': 'citalopram', 'type': 'Chemical', 'start': 855, 'end': 865, 'mesh': 'D015283'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 885, 'end': 894, 'mesh': 'D012701'}]"
+932,20635749,Severe congestive heart failure patient on amiodarone presenting with myxedemic coma: a case report.,"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.","[{'text': 'congestive heart failure', 'type': 'Disease', 'start': 7, 'end': 31, 'mesh': 'D006333'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 43, 'end': 53, 'mesh': 'D000638'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 153, 'end': 163, 'mesh': 'D000638'}, {'text': 'hypothyroidism', 'type': 'Disease', 'start': 172, 'end': 186, 'mesh': 'D007037'}, {'text': 'congestive heart failure', 'type': 'Disease', 'start': 212, 'end': 236, 'mesh': 'D006333'}, {'text': 'CHF', 'type': 'Disease', 'start': 238, 'end': 241, 'mesh': 'D006333'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 355, 'end': 365, 'mesh': 'D000638'}, {'text': 'thyroxine', 'type': 'Chemical', 'start': 528, 'end': 537, 'mesh': 'D013974'}, {'text': 'T4', 'type': 'Chemical', 'start': 539, 'end': 541, 'mesh': 'D013974'}, {'text': 'tri-iodo-thyronine', 'type': 'Chemical', 'start': 558, 'end': 576, 'mesh': 'D014284'}, {'text': 'T3', 'type': 'Chemical', 'start': 578, 'end': 580, 'mesh': 'D014284'}, {'text': 'CHF', 'type': 'Disease', 'start': 597, 'end': 600, 'mesh': 'D006333'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 604, 'end': 614, 'mesh': 'D000638'}, {'text': 'hypothyroidism', 'type': 'Disease', 'start': 663, 'end': 677, 'mesh': 'D007037'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 850, 'end': 860, 'mesh': 'D000638'}, {'text': 'CHF', 'type': 'Disease', 'start': 867, 'end': 870, 'mesh': 'D006333'}, {'text': 'CHF', 'type': 'Disease', 'start': 1029, 'end': 1032, 'mesh': 'D006333'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1058, 'end': 1069, 'mesh': 'D007022'}, {'text': 'weakness', 'type': 'Disease', 'start': 1071, 'end': 1079, 'mesh': 'D018908'}]"
+933,20394767,"Fear-potentiated startle, but not light-enhanced startle, is enhanced by anxiogenic drugs.","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 FPS.","[{'text': 'startle', 'type': 'Disease', 'start': 17, 'end': 24, 'mesh': 'D012021'}, {'text': 'startle', 'type': 'Disease', 'start': 49, 'end': 56, 'mesh': 'D012021'}, {'text': 'startle', 'type': 'Disease', 'start': 136, 'end': 143, 'mesh': 'D012021'}, {'text': 'anxiety', 'type': 'Disease', 'start': 181, 'end': 188, 'mesh': 'D001008'}, {'text': 'startle', 'type': 'Disease', 'start': 282, 'end': 289, 'mesh': 'D012021'}, {'text': 'yohimbine', 'type': 'Chemical', 'start': 746, 'end': 755, 'mesh': 'D015016'}, {'text': '5-HT', 'type': 'Chemical', 'start': 777, 'end': 781, 'mesh': 'D012701'}, {'text': 'm-chlorophenylpiperazine', 'type': 'Chemical', 'start': 803, 'end': 827, 'mesh': 'C015068'}, {'text': 'mCPP', 'type': 'Chemical', 'start': 829, 'end': 833, 'mesh': 'C015068'}, {'text': 'GABA', 'type': 'Chemical', 'start': 856, 'end': 860, 'mesh': 'D005680'}, {'text': 'pentylenetetrazole', 'type': 'Chemical', 'start': 889, 'end': 907, 'mesh': 'D010433'}, {'text': 'PTZ', 'type': 'Chemical', 'start': 909, 'end': 912, 'mesh': 'D010433'}, {'text': 'mCPP', 'type': 'Chemical', 'start': 1025, 'end': 1029, 'mesh': 'C015068'}, {'text': 'yohimbine', 'type': 'Chemical', 'start': 1059, 'end': 1068, 'mesh': 'D015016'}, {'text': 'yohimbine', 'type': 'Chemical', 'start': 1113, 'end': 1122, 'mesh': 'D015016'}, {'text': 'startle', 'type': 'Disease', 'start': 1142, 'end': 1149, 'mesh': 'D012021'}, {'text': 'mCPP', 'type': 'Chemical', 'start': 1178, 'end': 1182, 'mesh': 'C015068'}, {'text': 'startle', 'type': 'Disease', 'start': 1203, 'end': 1210, 'mesh': 'D012021'}, {'text': 'PTZ', 'type': 'Chemical', 'start': 1239, 'end': 1242, 'mesh': 'D010433'}, {'text': 'startle', 'type': 'Disease', 'start': 1263, 'end': 1270, 'mesh': 'D012021'}]"
+934,19203554,Proteinase 3-antineutrophil cytoplasmic antibody-(PR3-ANCA) positive necrotizing glomerulonephritis after restarting sulphasalazine treatment.,"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.","[{'text': 'glomerulonephritis', 'type': 'Disease', 'start': 81, 'end': 99, 'mesh': 'D005921'}, {'text': 'sulphasalazine', 'type': 'Chemical', 'start': 117, 'end': 131, 'mesh': 'D012460'}, {'text': 'ulcerative colitis', 'type': 'Disease', 'start': 168, 'end': 186, 'mesh': 'D003093'}, {'text': 'red eyes', 'type': 'Disease', 'start': 197, 'end': 205, 'mesh': 'D005128'}, {'text': 'pleural effusion', 'type': 'Disease', 'start': 207, 'end': 223, 'mesh': 'D010996'}, {'text': 'eosinophilia', 'type': 'Disease', 'start': 225, 'end': 237, 'mesh': 'D004802'}, {'text': 'urinary abnormalities', 'type': 'Disease', 'start': 242, 'end': 263, 'mesh': 'D001745'}, {'text': 'sulphasalazine', 'type': 'Chemical', 'start': 284, 'end': 298, 'mesh': 'D012460'}, {'text': 'segmental necrotizing glomerulonephritis', 'type': 'Disease', 'start': 355, 'end': 395, 'mesh': 'D005923'}, {'text': 'pleural effusions', 'type': 'Disease', 'start': 665, 'end': 682, 'mesh': 'D010996'}, {'text': 'sulphasalazine', 'type': 'Chemical', 'start': 743, 'end': 757, 'mesh': 'D012460'}, {'text': 'fever', 'type': 'Disease', 'start': 796, 'end': 801, 'mesh': 'D005334'}, {'text': 'red eyes', 'type': 'Disease', 'start': 803, 'end': 811, 'mesh': 'D005128'}, {'text': 'chest pain', 'type': 'Disease', 'start': 813, 'end': 823, 'mesh': 'D002637'}, {'text': 'pleural effusions', 'type': 'Disease', 'start': 871, 'end': 888, 'mesh': 'D010996'}, {'text': 'steroid', 'type': 'Chemical', 'start': 903, 'end': 910, 'mesh': 'D013256'}, {'text': 'pleural effusion', 'type': 'Disease', 'start': 1017, 'end': 1033, 'mesh': 'D010996'}, {'text': 'steroid', 'type': 'Chemical', 'start': 1060, 'end': 1067, 'mesh': 'D013256'}, {'text': 'pleural effusion', 'type': 'Disease', 'start': 1081, 'end': 1097, 'mesh': 'D010996'}, {'text': 'sulphasalazine', 'type': 'Chemical', 'start': 1181, 'end': 1195, 'mesh': 'D012460'}, {'text': 'glomerulonephritis', 'type': 'Disease', 'start': 1237, 'end': 1255, 'mesh': 'D005921'}]"
+935,17049862,Is phenytoin administration safe in a hypothermic child?,"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.","[{'text': 'phenytoin', 'type': 'Chemical', 'start': 3, 'end': 12, 'mesh': 'D010672'}, {'text': 'hypothermic', 'type': 'Disease', 'start': 38, 'end': 49, 'mesh': 'D007035'}, {'text': 'Chiari malformation', 'type': 'Disease', 'start': 79, 'end': 98, 'mesh': 'D001139'}, {'text': 'hypothermic', 'type': 'Disease', 'start': 286, 'end': 297, 'mesh': 'D007035'}, {'text': 'phenytoin', 'type': 'Chemical', 'start': 311, 'end': 320, 'mesh': 'D010672'}, {'text': 'seizure', 'type': 'Disease', 'start': 379, 'end': 386, 'mesh': 'D012640'}, {'text': 'phenytoin', 'type': 'Chemical', 'start': 410, 'end': 419, 'mesh': 'D010672'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 471, 'end': 482, 'mesh': 'D001919'}, {'text': 'atropine', 'type': 'Chemical', 'start': 498, 'end': 506, 'mesh': 'D001285'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 511, 'end': 521, 'mesh': 'D004837'}, {'text': 'phenytoin', 'type': 'Chemical', 'start': 557, 'end': 566, 'mesh': 'D010672'}, {'text': 'hypothermia', 'type': 'Disease', 'start': 571, 'end': 582, 'mesh': 'D007035'}, {'text': 'phenytoin', 'type': 'Chemical', 'start': 618, 'end': 627, 'mesh': 'D010672'}, {'text': 'hypothermia', 'type': 'Disease', 'start': 647, 'end': 658, 'mesh': 'D007035'}, {'text': 'phenytoin', 'type': 'Chemical', 'start': 712, 'end': 721, 'mesh': 'D010672'}]"
+936,16225977,Amisulpride related tic-like symptoms in an adolescent schizophrenic.,"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.","[{'text': 'Amisulpride', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'C012052'}, {'text': 'tic-like symptoms', 'type': 'Disease', 'start': 20, 'end': 37, 'mesh': 'D013981'}, {'text': 'schizophrenic', 'type': 'Disease', 'start': 55, 'end': 68, 'mesh': 'D012559'}, {'text': 'Tic disorders', 'type': 'Disease', 'start': 70, 'end': 83, 'mesh': 'D013981'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 146, 'end': 157, 'mesh': 'D018967'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 159, 'end': 169, 'mesh': 'C076029'}, {'text': 'ziprasidone', 'type': 'Chemical', 'start': 174, 'end': 185, 'mesh': 'C092292'}, {'text': 'tic-like symptoms', 'type': 'Disease', 'start': 233, 'end': 250, 'mesh': 'D013981'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 321, 'end': 331, 'mesh': 'C069541'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 335, 'end': 344, 'mesh': 'D003024'}, {'text': 'schizophrenic', 'type': 'Disease', 'start': 376, 'end': 389, 'mesh': 'D012559'}, {'text': 'involuntary eye-blinking movements', 'type': 'Disease', 'start': 413, 'end': 447, 'mesh': 'D020820'}, {'text': 'amisulpride', 'type': 'Chemical', 'start': 466, 'end': 477, 'mesh': 'C012052'}, {'text': 'tic-like symptoms', 'type': 'Disease', 'start': 511, 'end': 528, 'mesh': 'D013981'}, {'text': 'amisulpride', 'type': 'Chemical', 'start': 578, 'end': 589, 'mesh': 'C012052'}, {'text': 'psychosis', 'type': 'Disease', 'start': 627, 'end': 636, 'mesh': 'D011605'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 726, 'end': 736, 'mesh': 'C069541'}, {'text': 'tic-like symptoms', 'type': 'Disease', 'start': 871, 'end': 888, 'mesh': 'D013981'}, {'text': 'tic-like symptoms', 'type': 'Disease', 'start': 998, 'end': 1015, 'mesh': 'D013981'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 1116, 'end': 1126, 'mesh': 'C069541'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 1128, 'end': 1137, 'mesh': 'D003024'}, {'text': 'amisulpride', 'type': 'Chemical', 'start': 1142, 'end': 1153, 'mesh': 'C012052'}]"
+937,12852481,Comparison of developmental toxicology of aspirin (acetylsalicylic acid) in rats using selected dosing paradigms.,"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.","[{'text': 'aspirin', 'type': 'Chemical', 'start': 42, 'end': 49, 'mesh': 'D001241'}, {'text': 'acetylsalicylic acid', 'type': 'Chemical', 'start': 51, 'end': 71, 'mesh': 'D001241'}, {'text': 'developmental anomalies', 'type': 'Disease', 'start': 236, 'end': 259, 'mesh': 'D000014'}, {'text': 'Aspirin', 'type': 'Chemical', 'start': 327, 'end': 334, 'mesh': 'D001241'}, {'text': 'acetylsalicylic acid', 'type': 'Chemical', 'start': 336, 'end': 356, 'mesh': 'D001241'}, {'text': 'ASA', 'type': 'Chemical', 'start': 358, 'end': 361, 'mesh': 'D001241'}, {'text': 'developmental anomalies', 'type': 'Disease', 'start': 423, 'end': 446, 'mesh': 'D000014'}, {'text': 'ASA', 'type': 'Chemical', 'start': 605, 'end': 608, 'mesh': 'D001241'}, {'text': 'ASA', 'type': 'Chemical', 'start': 776, 'end': 779, 'mesh': 'D001241'}, {'text': 'gastrointestinal toxicity', 'type': 'Disease', 'start': 965, 'end': 990, 'mesh': 'D005767'}, {'text': 'malformations', 'type': 'Disease', 'start': 1032, 'end': 1045, 'mesh': 'D000014'}, {'text': 'ASA', 'type': 'Chemical', 'start': 1051, 'end': 1054, 'mesh': 'D001241'}, {'text': 'ASA', 'type': 'Chemical', 'start': 1105, 'end': 1108, 'mesh': 'D001241'}, {'text': 'ventricular septal defects', 'type': 'Disease', 'start': 1474, 'end': 1500, 'mesh': 'D006345'}, {'text': 'VSDs', 'type': 'Disease', 'start': 1502, 'end': 1506, 'mesh': 'D006345'}, {'text': 'midline defects', 'type': 'Disease', 'start': 1512, 'end': 1527, 'mesh': 'D009436'}, {'text': 'MDs', 'type': 'Disease', 'start': 1529, 'end': 1532, 'mesh': 'D009436'}, {'text': 'diaphragmatic hernia', 'type': 'Disease', 'start': 1546, 'end': 1566, 'mesh': 'D065630'}, {'text': 'DH', 'type': 'Disease', 'start': 1568, 'end': 1570, 'mesh': 'D065630'}, {'text': 'MDs', 'type': 'Disease', 'start': 1573, 'end': 1576, 'mesh': 'D009436'}, {'text': 'VSDs', 'type': 'Disease', 'start': 1582, 'end': 1586, 'mesh': 'D006345'}, {'text': 'malformations', 'type': 'Disease', 'start': 1664, 'end': 1677, 'mesh': 'D000014'}, {'text': 'ASA', 'type': 'Chemical', 'start': 1691, 'end': 1694, 'mesh': 'D001241'}, {'text': 'malformations', 'type': 'Disease', 'start': 1731, 'end': 1744, 'mesh': 'D000014'}, {'text': 'DH', 'type': 'Disease', 'start': 1770, 'end': 1772, 'mesh': 'D065630'}, {'text': 'MD', 'type': 'Disease', 'start': 1774, 'end': 1776, 'mesh': 'D009436'}, {'text': 'VSD', 'type': 'Disease', 'start': 1782, 'end': 1785, 'mesh': 'D006345'}, {'text': 'VSD', 'type': 'Disease', 'start': 1816, 'end': 1819, 'mesh': 'D006345'}, {'text': 'DH', 'type': 'Disease', 'start': 1878, 'end': 1880, 'mesh': 'D065630'}, {'text': 'MD', 'type': 'Disease', 'start': 1885, 'end': 1887, 'mesh': 'D009436'}, {'text': 'VSD', 'type': 'Disease', 'start': 1966, 'end': 1969, 'mesh': 'D006345'}, {'text': 'developmental anomalies', 'type': 'Disease', 'start': 2043, 'end': 2066, 'mesh': 'D000014'}, {'text': 'VSD', 'type': 'Disease', 'start': 2127, 'end': 2130, 'mesh': 'D006345'}, {'text': 'hydrocephalus', 'type': 'Disease', 'start': 2150, 'end': 2163, 'mesh': 'D006849'}, {'text': 'malformations', 'type': 'Disease', 'start': 2199, 'end': 2212, 'mesh': 'D000014'}, {'text': 'ASA', 'type': 'Chemical', 'start': 2231, 'end': 2234, 'mesh': 'D001241'}, {'text': 'malformations', 'type': 'Disease', 'start': 2407, 'end': 2420, 'mesh': 'D000014'}, {'text': 'ASA', 'type': 'Chemical', 'start': 2533, 'end': 2536, 'mesh': 'D001241'}]"
+938,11858397,Torsade de pointes induced by metoclopramide in an elderly woman with preexisting complete left bundle branch block.,"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.","[{'text': 'Torsade de pointes', 'type': 'Disease', 'start': 0, 'end': 18, 'mesh': 'D016171'}, {'text': 'metoclopramide', 'type': 'Chemical', 'start': 30, 'end': 44, 'mesh': 'D008787'}, {'text': 'left bundle branch block', 'type': 'Disease', 'start': 91, 'end': 115, 'mesh': 'D002037'}, {'text': 'long QT syndrome', 'type': 'Disease', 'start': 173, 'end': 189, 'mesh': 'D008133'}, {'text': 'torsade de pointes', 'type': 'Disease', 'start': 194, 'end': 212, 'mesh': 'D016171'}, {'text': 'metoclopramide', 'type': 'Chemical', 'start': 253, 'end': 267, 'mesh': 'D008787'}, {'text': 'procainamide', 'type': 'Chemical', 'start': 393, 'end': 405, 'mesh': 'D011342'}, {'text': 'left bundle branch block', 'type': 'Disease', 'start': 466, 'end': 490, 'mesh': 'D002037'}, {'text': 'torsade de pointes', 'type': 'Disease', 'start': 505, 'end': 523, 'mesh': 'D016171'}, {'text': 'metoclopramide', 'type': 'Chemical', 'start': 569, 'end': 583, 'mesh': 'D008787'}, {'text': 'torsade de pointes', 'type': 'Disease', 'start': 613, 'end': 631, 'mesh': 'D016171'}, {'text': 'cisapride', 'type': 'Chemical', 'start': 637, 'end': 646, 'mesh': 'D020117'}, {'text': 'erythromycin', 'type': 'Chemical', 'start': 651, 'end': 663, 'mesh': 'D004917'}, {'text': 'metoclopramide', 'type': 'Chemical', 'start': 850, 'end': 864, 'mesh': 'D008787'}, {'text': 'torsade de pointes', 'type': 'Disease', 'start': 874, 'end': 892, 'mesh': 'D016171'}, {'text': 'Metoclopramide', 'type': 'Chemical', 'start': 905, 'end': 919, 'mesh': 'D008787'}, {'text': 'torsade de pointes', 'type': 'Disease', 'start': 973, 'end': 991, 'mesh': 'D016171'}]"
+939,11009181,Apomorphine: an underutilized therapy for Parkinson's disease.,"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.","[{'text': 'Apomorphine', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D001058'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 42, 'end': 61, 'mesh': 'D010300'}, {'text': 'Apomorphine', 'type': 'Chemical', 'start': 63, 'end': 74, 'mesh': 'D001058'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 138, 'end': 157, 'mesh': 'D010300'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 273, 'end': 292, 'mesh': 'D010300'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 327, 'end': 338, 'mesh': 'D001058'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 493, 'end': 504, 'mesh': 'D001058'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 590, 'end': 598, 'mesh': 'D007980'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 608, 'end': 619, 'mesh': 'D001058'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 745, 'end': 756, 'mesh': 'D001058'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 930, 'end': 938, 'mesh': 'D004298'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 1055, 'end': 1066, 'mesh': 'D001058'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 1174, 'end': 1185, 'mesh': 'D001058'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1248, 'end': 1256, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 1265, 'end': 1276, 'mesh': 'D004409'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 1316, 'end': 1327, 'mesh': 'D001058'}, {'text': 'psychiatric', 'type': 'Disease', 'start': 1407, 'end': 1418, 'mesh': 'D001523'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 1505, 'end': 1516, 'mesh': 'D001058'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 1542, 'end': 1561, 'mesh': 'D010300'}]"
+940,8988571,Fatal excited delirium following cocaine use: epidemiologic findings provide new evidence for mechanisms of cocaine toxicity.,"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.","[{'text': 'delirium', 'type': 'Disease', 'start': 14, 'end': 22, 'mesh': 'D003693'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 33, 'end': 40, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 108, 'end': 115, 'mesh': 'D003042'}, {'text': 'toxicity', 'type': 'Disease', 'start': 116, 'end': 124, 'mesh': 'D064420'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 165, 'end': 172, 'mesh': 'D003042'}, {'text': 'delirium', 'type': 'Disease', 'start': 189, 'end': 197, 'mesh': 'D003693'}, {'text': 'EDDs', 'type': 'Disease', 'start': 199, 'end': 203, 'mesh': 'D003693'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 275, 'end': 282, 'mesh': 'D003042'}, {'text': 'EDDs', 'type': 'Disease', 'start': 342, 'end': 346, 'mesh': 'D003693'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 392, 'end': 399, 'mesh': 'D003042'}, {'text': 'overdose', 'type': 'Disease', 'start': 400, 'end': 408, 'mesh': 'D062787'}, {'text': 'delirium', 'type': 'Disease', 'start': 425, 'end': 433, 'mesh': 'D003693'}, {'text': 'EDDs', 'type': 'Disease', 'start': 459, 'end': 463, 'mesh': 'D003693'}, {'text': 'hyperthermia', 'type': 'Disease', 'start': 729, 'end': 741, 'mesh': 'D005334'}, {'text': 'EDDs', 'type': 'Disease', 'start': 778, 'end': 782, 'mesh': 'D003693'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 805, 'end': 812, 'mesh': 'D003042'}, {'text': 'benzoylecgonine', 'type': 'Chemical', 'start': 817, 'end': 832, 'mesh': 'C005618'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 971, 'end': 978, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1044, 'end': 1051, 'mesh': 'D003042'}, {'text': 'agitation', 'type': 'Disease', 'start': 1073, 'end': 1082, 'mesh': 'D011595'}, {'text': 'delirium', 'type': 'Disease', 'start': 1084, 'end': 1092, 'mesh': 'D003693'}, {'text': 'rhabdomyolysis', 'type': 'Disease', 'start': 1121, 'end': 1135, 'mesh': 'D012206'}, {'text': 'sudden death', 'type': 'Disease', 'start': 1141, 'end': 1153, 'mesh': 'D003645'}]"
+941,6615052,"Heparin-induced thrombocytopenia, thrombosis, and hemorrhage.","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 indicated.","[{'text': 'Heparin', 'type': 'Chemical', 'start': 0, 'end': 7, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 16, 'end': 32, 'mesh': 'D013921'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 34, 'end': 44, 'mesh': 'D013927'}, {'text': 'hemorrhage', 'type': 'Disease', 'start': 50, 'end': 60, 'mesh': 'D006470'}, {'text': 'heparin', 'type': 'Chemical', 'start': 88, 'end': 95, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 104, 'end': 120, 'mesh': 'D013921'}, {'text': 'hemorrhage', 'type': 'Disease', 'start': 184, 'end': 194, 'mesh': 'D006470'}, {'text': 'thromboembolic', 'type': 'Disease', 'start': 216, 'end': 230, 'mesh': 'D013923'}, {'text': 'heparin', 'type': 'Chemical', 'start': 260, 'end': 267, 'mesh': 'D006493'}, {'text': 'a falling platelet count', 'type': 'Disease', 'start': 301, 'end': 325, 'mesh': 'D001791'}, {'text': 'heparin', 'type': 'Chemical', 'start': 351, 'end': 358, 'mesh': 'D006493'}, {'text': 'heparin', 'type': 'Chemical', 'start': 418, 'end': 425, 'mesh': 'D006493'}, {'text': 'heparin', 'type': 'Chemical', 'start': 491, 'end': 498, 'mesh': 'D006493'}, {'text': 'heparin', 'type': 'Chemical', 'start': 779, 'end': 786, 'mesh': 'D006493'}, {'text': 'heparin', 'type': 'Chemical', 'start': 893, 'end': 900, 'mesh': 'D006493'}, {'text': 'platelet aggregation', 'type': 'Disease', 'start': 902, 'end': 922, 'mesh': 'D001791'}, {'text': 'heparin', 'type': 'Chemical', 'start': 1010, 'end': 1017, 'mesh': 'D006493'}]"
+942,3952818,Cardiac toxicity of 5-fluorouracil. Report of a case of spontaneous angina.,"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.","[{'text': 'Cardiac toxicity', 'type': 'Disease', 'start': 0, 'end': 16, 'mesh': 'D066126'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 20, 'end': 34, 'mesh': 'D005472'}, {'text': 'angina', 'type': 'Disease', 'start': 68, 'end': 74, 'mesh': 'D000787'}, {'text': 'colon carcinoma', 'type': 'Disease', 'start': 111, 'end': 126, 'mesh': 'D003110'}, {'text': 'metastasis', 'type': 'Disease', 'start': 137, 'end': 147, 'mesh': 'D009362'}, {'text': 'chest pain', 'type': 'Disease', 'start': 162, 'end': 172, 'mesh': 'D002637'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 179, 'end': 193, 'mesh': 'D005472'}, {'text': '5-FU', 'type': 'Chemical', 'start': 195, 'end': 199, 'mesh': 'D005472'}, {'text': ""Prinzmetal's angina"", 'type': 'Disease', 'start': 289, 'end': 308, 'mesh': 'D000788'}, {'text': 'chest pain', 'type': 'Disease', 'start': 314, 'end': 324, 'mesh': 'D002637'}, {'text': 'nifedipine', 'type': 'Chemical', 'start': 348, 'end': 358, 'mesh': 'D009543'}, {'text': 'coronary spasm', 'type': 'Disease', 'start': 384, 'end': 398, 'mesh': 'D003329'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 419, 'end': 433, 'mesh': 'D066126'}, {'text': '5-FU', 'type': 'Chemical', 'start': 441, 'end': 445, 'mesh': 'D005472'}, {'text': 'calcium', 'type': 'Chemical', 'start': 456, 'end': 463, 'mesh': 'D002118'}, {'text': '5-FU', 'type': 'Chemical', 'start': 531, 'end': 535, 'mesh': 'D005472'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 536, 'end': 550, 'mesh': 'D066126'}]"
+943,3084782,Toxicity due to remission inducing drugs in rheumatoid arthritis. Association with HLA-B35 and Cw4 antigens.,"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.","[{'text': 'Toxicity', 'type': 'Disease', 'start': 0, 'end': 8, 'mesh': 'D064420'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 44, 'end': 64, 'mesh': 'D001172'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 135, 'end': 155, 'mesh': 'D001172'}, {'text': 'RA', 'type': 'Disease', 'start': 157, 'end': 159, 'mesh': 'D001172'}, {'text': 'toxicity', 'type': 'Disease', 'start': 175, 'end': 183, 'mesh': 'D064420'}, {'text': 'toxicity', 'type': 'Disease', 'start': 237, 'end': 245, 'mesh': 'D064420'}, {'text': 'nephritis', 'type': 'Disease', 'start': 363, 'end': 372, 'mesh': 'D009393'}, {'text': 'dermatitis', 'type': 'Disease', 'start': 377, 'end': 387, 'mesh': 'D003872'}, {'text': 'Tiopronin', 'type': 'Chemical', 'start': 395, 'end': 404, 'mesh': 'D008625'}, {'text': 'D-Penicillamine', 'type': 'Chemical', 'start': 408, 'end': 423, 'mesh': 'D010396'}, {'text': 'dermatitis', 'type': 'Disease', 'start': 481, 'end': 491, 'mesh': 'D003872'}, {'text': 'gold', 'type': 'Chemical', 'start': 499, 'end': 503, 'mesh': 'D006046'}, {'text': 'thiosulphate', 'type': 'Chemical', 'start': 504, 'end': 516, 'mesh': '-1'}, {'text': 'RA', 'type': 'Disease', 'start': 607, 'end': 609, 'mesh': 'D001172'}, {'text': 'Tiopronin', 'type': 'Chemical', 'start': 625, 'end': 634, 'mesh': 'D008625'}, {'text': 'nephritis', 'type': 'Disease', 'start': 643, 'end': 652, 'mesh': 'D009393'}]"
+944,430165,Transient hemiparesis: a rare manifestation of diphenylhydantoin toxicity. Report of two cases.,"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.","[{'text': 'hemiparesis', 'type': 'Disease', 'start': 10, 'end': 21, 'mesh': 'D010291'}, {'text': 'diphenylhydantoin', 'type': 'Chemical', 'start': 47, 'end': 64, 'mesh': 'D010672'}, {'text': 'toxicity', 'type': 'Disease', 'start': 65, 'end': 73, 'mesh': 'D064420'}, {'text': 'diphenylhydantoin', 'type': 'Chemical', 'start': 129, 'end': 146, 'mesh': 'D010672'}, {'text': 'DPH', 'type': 'Chemical', 'start': 148, 'end': 151, 'mesh': 'D010672'}, {'text': 'overdose', 'type': 'Disease', 'start': 153, 'end': 161, 'mesh': 'D062787'}, {'text': 'cerebellar dysfunction', 'type': 'Disease', 'start': 227, 'end': 249, 'mesh': 'D002526'}, {'text': 'hemiparesis', 'type': 'Disease', 'start': 391, 'end': 402, 'mesh': 'D010291'}, {'text': 'DPH', 'type': 'Chemical', 'start': 410, 'end': 413, 'mesh': 'D010672'}, {'text': 'overdose', 'type': 'Disease', 'start': 414, 'end': 422, 'mesh': 'D062787'}, {'text': 'DPH', 'type': 'Chemical', 'start': 454, 'end': 457, 'mesh': 'D010672'}, {'text': 'cerebral damage', 'type': 'Disease', 'start': 507, 'end': 522, 'mesh': 'D001927'}, {'text': 'DPH', 'type': 'Chemical', 'start': 546, 'end': 549, 'mesh': 'D010672'}, {'text': 'toxicity', 'type': 'Disease', 'start': 550, 'end': 558, 'mesh': 'D064420'}]"
+945,16600756,Nerve growth factor and prostaglandins in the urine of female patients with overactive bladder.,"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.","[{'text': 'prostaglandins', 'type': 'Chemical', 'start': 24, 'end': 38, 'mesh': 'D011453'}, {'text': 'overactive bladder', 'type': 'Disease', 'start': 76, 'end': 94, 'mesh': 'D053201'}, {'text': 'PGs', 'type': 'Chemical', 'start': 113, 'end': 116, 'mesh': 'D011453'}, {'text': 'PGs', 'type': 'Chemical', 'start': 274, 'end': 277, 'mesh': 'D011453'}, {'text': 'OAB', 'type': 'Disease', 'start': 292, 'end': 295, 'mesh': 'D053201'}, {'text': 'OAB', 'type': 'Disease', 'start': 360, 'end': 363, 'mesh': 'D053201'}, {'text': 'PGE2', 'type': 'Chemical', 'start': 544, 'end': 548, 'mesh': 'D015232'}, {'text': 'PGF2alpha', 'type': 'Chemical', 'start': 550, 'end': 559, 'mesh': 'D015237'}, {'text': 'PGI2', 'type': 'Chemical', 'start': 564, 'end': 568, 'mesh': 'D011464'}, {'text': 'PG', 'type': 'Chemical', 'start': 706, 'end': 708, 'mesh': 'D011453'}, {'text': 'OAB', 'type': 'Disease', 'start': 753, 'end': 756, 'mesh': 'D053201'}, {'text': 'PGE2', 'type': 'Chemical', 'start': 794, 'end': 798, 'mesh': 'D015232'}, {'text': 'PGF2alpha', 'type': 'Chemical', 'start': 803, 'end': 812, 'mesh': 'D015237'}, {'text': 'OAB', 'type': 'Disease', 'start': 859, 'end': 862, 'mesh': 'D053201'}, {'text': 'PGI2', 'type': 'Chemical', 'start': 914, 'end': 918, 'mesh': 'D011464'}, {'text': 'OAB', 'type': 'Disease', 'start': 972, 'end': 975, 'mesh': 'D053201'}, {'text': 'OAB', 'type': 'Disease', 'start': 994, 'end': 997, 'mesh': 'D053201'}, {'text': 'PGE2', 'type': 'Chemical', 'start': 1006, 'end': 1010, 'mesh': 'D015232'}, {'text': 'PGF2alpha', 'type': 'Chemical', 'start': 1126, 'end': 1135, 'mesh': 'D015237'}, {'text': 'PGI2', 'type': 'Chemical', 'start': 1140, 'end': 1144, 'mesh': 'D011464'}, {'text': 'OAB', 'type': 'Disease', 'start': 1207, 'end': 1210, 'mesh': 'D053201'}, {'text': 'PGs', 'type': 'Chemical', 'start': 1233, 'end': 1236, 'mesh': 'D011453'}, {'text': 'OAB', 'type': 'Disease', 'start': 1280, 'end': 1283, 'mesh': 'D053201'}, {'text': 'OAB', 'type': 'Disease', 'start': 1380, 'end': 1383, 'mesh': 'D053201'}]"
+946,15686794,Acute low back pain during intravenous administration of amiodarone: a report of two cases.,"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.","[{'text': 'low back pain', 'type': 'Disease', 'start': 6, 'end': 19, 'mesh': 'D017116'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 57, 'end': 67, 'mesh': 'D000638'}, {'text': 'Amiodarone', 'type': 'Chemical', 'start': 92, 'end': 102, 'mesh': 'D000638'}, {'text': 'atrial fibrillation', 'type': 'Disease', 'start': 181, 'end': 200, 'mesh': 'D001281'}, {'text': 'AF', 'type': 'Disease', 'start': 202, 'end': 204, 'mesh': 'D001281'}, {'text': 'atrial fibrillation', 'type': 'Disease', 'start': 300, 'end': 319, 'mesh': 'D001281'}, {'text': 'low back pain', 'type': 'Disease', 'start': 358, 'end': 371, 'mesh': 'D017116'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 418, 'end': 428, 'mesh': 'D000638'}]"
+947,12760988,Postoperative myalgia after succinylcholine: no evidence for an inflammatory origin.,"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.","[{'text': 'Postoperative myalgia', 'type': 'Disease', 'start': 0, 'end': 21, 'mesh': 'D010149'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 28, 'end': 43, 'mesh': 'D013390'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 122, 'end': 137, 'mesh': 'D013390'}, {'text': 'postoperative myalgia', 'type': 'Disease', 'start': 141, 'end': 162, 'mesh': 'D010149'}, {'text': 'myalgia', 'type': 'Disease', 'start': 189, 'end': 196, 'mesh': 'D063806'}, {'text': 'inflammation', 'type': 'Disease', 'start': 215, 'end': 227, 'mesh': 'D007249'}, {'text': 'myalgia', 'type': 'Disease', 'start': 378, 'end': 385, 'mesh': 'D063806'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 417, 'end': 432, 'mesh': 'D013390'}, {'text': 'myalgia', 'type': 'Disease', 'start': 444, 'end': 451, 'mesh': 'D063806'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 508, 'end': 521, 'mesh': 'D003907'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 529, 'end': 544, 'mesh': 'D013390'}, {'text': 'myalgia', 'type': 'Disease', 'start': 590, 'end': 597, 'mesh': 'D063806'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 670, 'end': 683, 'mesh': 'D003907'}, {'text': 'myalgia', 'type': 'Disease', 'start': 704, 'end': 711, 'mesh': 'D063806'}, {'text': 'myalgia', 'type': 'Disease', 'start': 770, 'end': 777, 'mesh': 'D063806'}, {'text': 'myalgia', 'type': 'Disease', 'start': 930, 'end': 937, 'mesh': 'D063806'}, {'text': 'inflammation', 'type': 'Disease', 'start': 1013, 'end': 1025, 'mesh': 'D007249'}, {'text': 'myalgia', 'type': 'Disease', 'start': 1176, 'end': 1183, 'mesh': 'D063806'}, {'text': 'myalgia', 'type': 'Disease', 'start': 1209, 'end': 1216, 'mesh': 'D063806'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 1319, 'end': 1334, 'mesh': 'D013390'}, {'text': 'myalgia', 'type': 'Disease', 'start': 1346, 'end': 1353, 'mesh': 'D063806'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 1387, 'end': 1400, 'mesh': 'D003907'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 1408, 'end': 1423, 'mesh': 'D013390'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 1489, 'end': 1504, 'mesh': 'D013390'}, {'text': 'postoperative myalgia', 'type': 'Disease', 'start': 1513, 'end': 1534, 'mesh': 'D010149'}, {'text': 'postoperative myalgia', 'type': 'Disease', 'start': 1595, 'end': 1616, 'mesh': 'D010149'}, {'text': 'inflammation', 'type': 'Disease', 'start': 1678, 'end': 1690, 'mesh': 'D007249'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 1710, 'end': 1723, 'mesh': 'D003907'}, {'text': 'postoperative myalgia', 'type': 'Disease', 'start': 1752, 'end': 1773, 'mesh': 'D010149'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 1780, 'end': 1795, 'mesh': 'D013390'}]"
+948,12691807,Levodopa-induced oromandibular dystonia in progressive supranuclear palsy.,"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.","[{'text': 'Levodopa', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D007980'}, {'text': 'dystonia', 'type': 'Disease', 'start': 31, 'end': 39, 'mesh': 'D004421'}, {'text': 'progressive supranuclear palsy', 'type': 'Disease', 'start': 43, 'end': 73, 'mesh': 'D013494'}, {'text': 'Levodopa', 'type': 'Chemical', 'start': 75, 'end': 83, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 92, 'end': 103, 'mesh': 'D004409'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 126, 'end': 145, 'mesh': 'D010300'}, {'text': 'multiple system atrophy', 'type': 'Disease', 'start': 150, 'end': 173, 'mesh': 'D019578'}, {'text': 'dystonias', 'type': 'Disease', 'start': 183, 'end': 192, 'mesh': 'D004421'}, {'text': 'progressive supranuclear palsy', 'type': 'Disease', 'start': 219, 'end': 249, 'mesh': 'D013494'}, {'text': 'PSP', 'type': 'Disease', 'start': 251, 'end': 254, 'mesh': 'D013494'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 314, 'end': 322, 'mesh': 'D007980'}, {'text': 'Oromandibular dystonia', 'type': 'Disease', 'start': 331, 'end': 353, 'mesh': 'D008538'}, {'text': 'OMD', 'type': 'Disease', 'start': 355, 'end': 358, 'mesh': 'D008538'}, {'text': 'PSP', 'type': 'Disease', 'start': 365, 'end': 368, 'mesh': 'D013494'}, {'text': 'PSP', 'type': 'Disease', 'start': 472, 'end': 475, 'mesh': 'D013494'}]"
+949,12600698,Protective effect of edaravone against streptomycin-induced vestibulotoxicity in the guinea pig.,"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.","[{'text': 'edaravone', 'type': 'Chemical', 'start': 21, 'end': 30, 'mesh': 'C005435'}, {'text': 'streptomycin', 'type': 'Chemical', 'start': 39, 'end': 51, 'mesh': 'D013307'}, {'text': 'vestibulotoxicity', 'type': 'Disease', 'start': 60, 'end': 77, 'mesh': 'D015837'}, {'text': 'streptomycin', 'type': 'Chemical', 'start': 136, 'end': 148, 'mesh': 'D013307'}, {'text': 'vestibulotoxicity', 'type': 'Disease', 'start': 157, 'end': 174, 'mesh': 'D015837'}, {'text': 'edaravone', 'type': 'Chemical', 'start': 178, 'end': 187, 'mesh': 'C005435'}, {'text': 'Edaravone', 'type': 'Chemical', 'start': 204, 'end': 213, 'mesh': 'C005435'}, {'text': 'cerebral infarction', 'type': 'Disease', 'start': 324, 'end': 343, 'mesh': 'D002544'}, {'text': 'Streptomycin', 'type': 'Chemical', 'start': 345, 'end': 357, 'mesh': 'D013307'}, {'text': 'edaravone', 'type': 'Chemical', 'start': 422, 'end': 431, 'mesh': 'C005435'}, {'text': 'edaravone', 'type': 'Chemical', 'start': 694, 'end': 703, 'mesh': 'C005435'}, {'text': 'edaravone', 'type': 'Chemical', 'start': 732, 'end': 741, 'mesh': 'C005435'}, {'text': 'streptomycin', 'type': 'Chemical', 'start': 753, 'end': 765, 'mesh': 'D013307'}, {'text': 'vestibulotoxicity', 'type': 'Disease', 'start': 774, 'end': 791, 'mesh': 'D015837'}]"
+950,12091028,Ketamine in war/tropical surgery (a final tribute to the racemic mixture).,"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.","[{'text': 'Ketamine', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D007649'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 130, 'end': 138, 'mesh': 'D007649'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 570, 'end': 576, 'mesh': 'D010100'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 608, 'end': 616, 'mesh': 'D003975'}, {'text': 'glycopyrrolate', 'type': 'Chemical', 'start': 618, 'end': 632, 'mesh': 'D006024'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 693, 'end': 701, 'mesh': 'D007649'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 748, 'end': 756, 'mesh': 'D007649'}, {'text': 'Diazepam', 'type': 'Chemical', 'start': 871, 'end': 879, 'mesh': 'D003975'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 963, 'end': 971, 'mesh': 'D007649'}, {'text': 'hallucinations', 'type': 'Disease', 'start': 1086, 'end': 1100, 'mesh': 'D006212'}, {'text': 'analgesia', 'type': 'Disease', 'start': 1187, 'end': 1196, 'mesh': 'D000699'}, {'text': 'glycopyrrolate', 'type': 'Chemical', 'start': 1271, 'end': 1285, 'mesh': 'D006024'}]"
+951,11860495,Steroid structure and pharmacological properties determine the anti-amnesic effects of pregnenolone sulphate in the passive avoidance task in rats.,"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.","[{'text': 'Steroid', 'type': 'Chemical', 'start': 0, 'end': 7, 'mesh': 'D013256'}, {'text': 'amnesic', 'type': 'Disease', 'start': 68, 'end': 75, 'mesh': 'D000647'}, {'text': 'pregnenolone sulphate', 'type': 'Chemical', 'start': 87, 'end': 108, 'mesh': 'C018370'}, {'text': 'Pregnenolone sulphate', 'type': 'Chemical', 'start': 148, 'end': 169, 'mesh': 'C018370'}, {'text': 'PREGS', 'type': 'Chemical', 'start': 171, 'end': 176, 'mesh': 'C018370'}, {'text': 'steroid', 'type': 'Chemical', 'start': 390, 'end': 397, 'mesh': 'D013256'}, {'text': 'PREGS', 'type': 'Chemical', 'start': 540, 'end': 545, 'mesh': 'C018370'}, {'text': 'N-methyl-d-aspartate', 'type': 'Chemical', 'start': 580, 'end': 600, 'mesh': 'D016202'}, {'text': 'gamma-aminobutyric acid', 'type': 'Chemical', 'start': 648, 'end': 671, 'mesh': 'D005680'}, {'text': 'GABA', 'type': 'Chemical', 'start': 686, 'end': 690, 'mesh': 'D005680'}, {'text': 'PREGS', 'type': 'Chemical', 'start': 708, 'end': 713, 'mesh': 'C018370'}, {'text': 'amnesic', 'type': 'Disease', 'start': 737, 'end': 744, 'mesh': 'D000647'}, {'text': 'GABA', 'type': 'Chemical', 'start': 771, 'end': 775, 'mesh': 'D005680'}, {'text': 'PREGS', 'type': 'Chemical', 'start': 911, 'end': 916, 'mesh': 'C018370'}, {'text': 'GABA', 'type': 'Chemical', 'start': 967, 'end': 971, 'mesh': 'D005680'}, {'text': '11-ketopregnenolone sulphate', 'type': 'Chemical', 'start': 1011, 'end': 1039, 'mesh': '-1'}, {'text': 'GABA', 'type': 'Chemical', 'start': 1070, 'end': 1074, 'mesh': 'D005680'}, {'text': 'epipregnanolone ([3beta-hydroxy-5beta-pregnan-20-one] sulphate', 'type': 'Chemical', 'start': 1093, 'end': 1155, 'mesh': 'C018370'}, {'text': 'GABA', 'type': 'Chemical', 'start': 1178, 'end': 1182, 'mesh': 'D005680'}, {'text': 'PREGS', 'type': 'Chemical', 'start': 1229, 'end': 1234, 'mesh': 'C018370'}, {'text': 'PREGS', 'type': 'Chemical', 'start': 1269, 'end': 1274, 'mesh': 'C018370'}, {'text': 'GABA', 'type': 'Chemical', 'start': 1289, 'end': 1293, 'mesh': 'D005680'}, {'text': 'PREGS', 'type': 'Chemical', 'start': 1344, 'end': 1349, 'mesh': 'C018370'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 1427, 'end': 1438, 'mesh': 'D012601'}, {'text': 'amnesia', 'type': 'Disease', 'start': 1447, 'end': 1454, 'mesh': 'D000647'}, {'text': 'PREGS', 'type': 'Chemical', 'start': 1461, 'end': 1466, 'mesh': 'C018370'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 1513, 'end': 1524, 'mesh': 'D012601'}, {'text': 'PREGS', 'type': 'Chemical', 'start': 1556, 'end': 1561, 'mesh': 'C018370'}, {'text': '11-ketopregnenolone sulphate', 'type': 'Chemical', 'start': 1563, 'end': 1591, 'mesh': '-1'}, {'text': 'epipregnanolone sulphate', 'type': 'Chemical', 'start': 1596, 'end': 1620, 'mesh': 'C018370'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 1651, 'end': 1662, 'mesh': 'D012601'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 1707, 'end': 1711, 'mesh': 'D016202'}, {'text': 'PREGS', 'type': 'Chemical', 'start': 1765, 'end': 1770, 'mesh': 'C018370'}, {'text': 'PREGS', 'type': 'Chemical', 'start': 1844, 'end': 1849, 'mesh': 'C018370'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 1936, 'end': 1947, 'mesh': 'D012601'}, {'text': 'amnesia', 'type': 'Disease', 'start': 1956, 'end': 1963, 'mesh': 'D000647'}, {'text': 'steroids', 'type': 'Chemical', 'start': 2076, 'end': 2084, 'mesh': 'D013256'}]"
+952,11752998,Preliminary efficacy assessment of intrathecal injection of an American formulation of adenosine in humans.,"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.","[{'text': 'adenosine', 'type': 'Chemical', 'start': 87, 'end': 96, 'mesh': 'D000241'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 155, 'end': 164, 'mesh': 'D000241'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 328, 'end': 337, 'mesh': 'D000241'}, {'text': 'hypersensitivity', 'type': 'Disease', 'start': 370, 'end': 386, 'mesh': 'D004342'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 517, 'end': 526, 'mesh': 'D000241'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 588, 'end': 597, 'mesh': 'D002211'}, {'text': 'hypersensitivity', 'type': 'Disease', 'start': 616, 'end': 632, 'mesh': 'D004342'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 848, 'end': 857, 'mesh': 'D000241'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 927, 'end': 936, 'mesh': 'D000241'}, {'text': 'pain', 'type': 'Disease', 'start': 1011, 'end': 1015, 'mesh': 'D010146'}, {'text': 'mechanical hyperalgesia', 'type': 'Disease', 'start': 1071, 'end': 1094, 'mesh': 'D006930'}, {'text': 'allodynia', 'type': 'Disease', 'start': 1099, 'end': 1108, 'mesh': 'D006930'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 1127, 'end': 1136, 'mesh': 'D002211'}, {'text': 'Adenosine', 'type': 'Chemical', 'start': 1173, 'end': 1182, 'mesh': 'D000241'}, {'text': 'pain', 'type': 'Disease', 'start': 1205, 'end': 1209, 'mesh': 'D010146'}, {'text': 'mechanical hyperalgesia', 'type': 'Disease', 'start': 1278, 'end': 1301, 'mesh': 'D006930'}, {'text': 'allodynia', 'type': 'Disease', 'start': 1306, 'end': 1315, 'mesh': 'D006930'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 1333, 'end': 1342, 'mesh': 'D002211'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 1403, 'end': 1412, 'mesh': 'D000241'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 1523, 'end': 1532, 'mesh': 'D000241'}, {'text': 'hypersensitivity', 'type': 'Disease', 'start': 1536, 'end': 1552, 'mesh': 'D004342'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 1623, 'end': 1632, 'mesh': 'D002211'}, {'text': 'neuropathic pain', 'type': 'Disease', 'start': 1749, 'end': 1765, 'mesh': 'D009437'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 1807, 'end': 1816, 'mesh': 'D000241'}]"
+953,10354657,Effect of lithium maintenance therapy on thyroid and parathyroid function.,"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.","[{'text': 'lithium', 'type': 'Chemical', 'start': 10, 'end': 17, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 116, 'end': 123, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 259, 'end': 266, 'mesh': 'D008094'}, {'text': 'thyroid disease', 'type': 'Disease', 'start': 366, 'end': 381, 'mesh': 'D013959'}, {'text': 'bipolar disorder', 'type': 'Disease', 'start': 547, 'end': 563, 'mesh': 'D001714'}, {'text': 'lithium', 'type': 'Chemical', 'start': 574, 'end': 581, 'mesh': 'D008094'}, {'text': 'psychiatric', 'type': 'Disease', 'start': 698, 'end': 709, 'mesh': 'D001523'}, {'text': 'calcium', 'type': 'Chemical', 'start': 822, 'end': 829, 'mesh': 'D002118'}, {'text': 'magnesium', 'type': 'Chemical', 'start': 831, 'end': 840, 'mesh': 'D008274'}, {'text': 'lithium', 'type': 'Chemical', 'start': 907, 'end': 914, 'mesh': 'D008094'}, {'text': 'Hypothyroidism', 'type': 'Disease', 'start': 959, 'end': 973, 'mesh': 'D007037'}, {'text': 'hypothyroid', 'type': 'Disease', 'start': 1030, 'end': 1041, 'mesh': 'D007037'}, {'text': 'thyroid illness', 'type': 'Disease', 'start': 1110, 'end': 1125, 'mesh': 'D013959'}, {'text': 'hypothyroidism', 'type': 'Disease', 'start': 1151, 'end': 1165, 'mesh': 'D007037'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1192, 'end': 1199, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1283, 'end': 1290, 'mesh': 'D008094'}, {'text': 'hypothyroidism', 'type': 'Disease', 'start': 1356, 'end': 1370, 'mesh': 'D007037'}, {'text': 'Magnesium', 'type': 'Chemical', 'start': 1426, 'end': 1435, 'mesh': 'D008274'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1458, 'end': 1465, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1519, 'end': 1526, 'mesh': 'D008094'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1538, 'end': 1545, 'mesh': 'D002118'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1618, 'end': 1625, 'mesh': 'D008094'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1672, 'end': 1679, 'mesh': 'D002118'}, {'text': 'thyroid illness', 'type': 'Disease', 'start': 1732, 'end': 1747, 'mesh': 'D013959'}, {'text': 'hypothyroidism', 'type': 'Disease', 'start': 1769, 'end': 1783, 'mesh': 'D007037'}, {'text': 'hypercalcemia', 'type': 'Disease', 'start': 1788, 'end': 1801, 'mesh': 'D006934'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1809, 'end': 1816, 'mesh': 'D008094'}]"
+954,10328196,Systemic toxicity following administration of sirolimus (formerly rapamycin) for psoriasis: association of capillary leak syndrome with apoptosis of lesional lymphocytes.,"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.","[{'text': 'toxicity', 'type': 'Disease', 'start': 9, 'end': 17, 'mesh': 'D064420'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 46, 'end': 55, 'mesh': 'D020123'}, {'text': 'rapamycin', 'type': 'Chemical', 'start': 66, 'end': 75, 'mesh': 'D020123'}, {'text': 'psoriasis', 'type': 'Disease', 'start': 81, 'end': 90, 'mesh': 'D011565'}, {'text': 'capillary leak syndrome', 'type': 'Disease', 'start': 107, 'end': 130, 'mesh': 'D019559'}, {'text': 'Sirolimus', 'type': 'Chemical', 'start': 183, 'end': 192, 'mesh': 'D020123'}, {'text': 'rapamycin', 'type': 'Chemical', 'start': 203, 'end': 212, 'mesh': 'D020123'}, {'text': 'psoriasis', 'type': 'Disease', 'start': 309, 'end': 318, 'mesh': 'D011565'}, {'text': 'capillary leak syndrome', 'type': 'Disease', 'start': 331, 'end': 354, 'mesh': 'D019559'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 385, 'end': 394, 'mesh': 'D020123'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 553, 'end': 562, 'mesh': 'D020123'}, {'text': 'capillary leak syndrome', 'type': 'Disease', 'start': 571, 'end': 594, 'mesh': 'D019559'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 689, 'end': 698, 'mesh': 'D020123'}, {'text': 'psoriasis', 'type': 'Disease', 'start': 720, 'end': 729, 'mesh': 'D011565'}, {'text': 'psoriasis', 'type': 'Disease', 'start': 791, 'end': 800, 'mesh': 'D011565'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 842, 'end': 855, 'mesh': 'D003907'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 931, 'end': 940, 'mesh': 'D020123'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 981, 'end': 990, 'mesh': 'D020123'}, {'text': 'fever', 'type': 'Disease', 'start': 999, 'end': 1004, 'mesh': 'D005334'}, {'text': 'anemia', 'type': 'Disease', 'start': 1006, 'end': 1012, 'mesh': 'D000740'}, {'text': 'capillary leak syndrome', 'type': 'Disease', 'start': 1018, 'end': 1041, 'mesh': 'D019559'}, {'text': 'psoriasis', 'type': 'Disease', 'start': 1239, 'end': 1248, 'mesh': 'D011565'}, {'text': 'capillary leak', 'type': 'Disease', 'start': 1261, 'end': 1275, 'mesh': 'D019559'}, {'text': 'inflammatory diseases', 'type': 'Disease', 'start': 1360, 'end': 1381, 'mesh': 'D007249'}]"
+955,9630698,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.,"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.","[{'text': 'glycine', 'type': 'Chemical', 'start': 20, 'end': 27, 'mesh': 'D005998'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 36, 'end': 40, 'mesh': 'D016202'}, {'text': 'glycine', 'type': 'Chemical', 'start': 217, 'end': 224, 'mesh': 'D005998'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 233, 'end': 237, 'mesh': 'D016202'}, {'text': 'Muscle rigidity', 'type': 'Disease', 'start': 631, 'end': 646, 'mesh': 'D009127'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 662, 'end': 673, 'mesh': 'D006220'}, {'text': '5,7-dichlorokynurenic acid', 'type': 'Chemical', 'start': 692, 'end': 718, 'mesh': 'C066192'}, {'text': '5,7-DCKA', 'type': 'Chemical', 'start': 720, 'end': 728, 'mesh': 'C066192'}, {'text': 'glycine', 'type': 'Chemical', 'start': 743, 'end': 750, 'mesh': 'D005998'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 892, 'end': 903, 'mesh': 'D006220'}, {'text': 'muscle rigidity', 'type': 'Disease', 'start': 912, 'end': 927, 'mesh': 'D009127'}, {'text': '5,7-DCKA', 'type': 'Chemical', 'start': 985, 'end': 993, 'mesh': 'C066192'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1130, 'end': 1141, 'mesh': 'D006220'}, {'text': 'glycine', 'type': 'Chemical', 'start': 1225, 'end': 1232, 'mesh': 'D005998'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 1241, 'end': 1245, 'mesh': 'D016202'}]"
+956,8480959,Efficacy and tolerability of lovastatin in 3390 women with moderate hypercholesterolemia.,"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.","[{'text': 'lovastatin', 'type': 'Chemical', 'start': 29, 'end': 39, 'mesh': 'D008148'}, {'text': 'hypercholesterolemia', 'type': 'Disease', 'start': 68, 'end': 88, 'mesh': 'D006937'}, {'text': 'lovastatin', 'type': 'Chemical', 'start': 140, 'end': 150, 'mesh': 'D008148'}, {'text': 'hypercholesterolemia', 'type': 'Disease', 'start': 174, 'end': 194, 'mesh': 'D006937'}, {'text': 'Lovastatin', 'type': 'Chemical', 'start': 240, 'end': 250, 'mesh': 'D008148'}, {'text': 'lovastatin', 'type': 'Chemical', 'start': 398, 'end': 408, 'mesh': 'D008148'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 747, 'end': 758, 'mesh': 'D002784'}, {'text': 'triglycerides', 'type': 'Chemical', 'start': 764, 'end': 777, 'mesh': 'D014280'}, {'text': 'lovastatin', 'type': 'Chemical', 'start': 901, 'end': 911, 'mesh': 'D008148'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 1016, 'end': 1027, 'mesh': 'D002784'}, {'text': 'triglycerides', 'type': 'Chemical', 'start': 1045, 'end': 1058, 'mesh': 'D014280'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 1093, 'end': 1104, 'mesh': 'D002784'}, {'text': 'lovastatin', 'type': 'Chemical', 'start': 1163, 'end': 1173, 'mesh': 'D008148'}, {'text': 'Cholesterol', 'type': 'Chemical', 'start': 1210, 'end': 1221, 'mesh': 'D002784'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 1252, 'end': 1263, 'mesh': 'D002784'}, {'text': 'Myopathy', 'type': 'Disease', 'start': 1525, 'end': 1533, 'mesh': 'D009135'}, {'text': 'creatine', 'type': 'Chemical', 'start': 1567, 'end': 1575, 'mesh': 'D003401'}, {'text': 'lovastatin', 'type': 'Chemical', 'start': 1710, 'end': 1720, 'mesh': 'D008148'}, {'text': 'lovastatin', 'type': 'Chemical', 'start': 1830, 'end': 1840, 'mesh': 'D008148'}, {'text': 'Lovastatin', 'type': 'Chemical', 'start': 1854, 'end': 1864, 'mesh': 'D008148'}, {'text': 'hypercholesterolemia', 'type': 'Disease', 'start': 1937, 'end': 1957, 'mesh': 'D006937'}]"
+957,7197363,REM sleep deprivation changes behavioral response to catecholaminergic and serotonergic receptor activation in rats.,"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.","[{'text': 'REM sleep deprivation', 'type': 'Disease', 'start': 0, 'end': 21, 'mesh': 'D012892'}, {'text': 'REM sleep deprivation', 'type': 'Disease', 'start': 132, 'end': 153, 'mesh': 'D012892'}, {'text': 'REMD', 'type': 'Disease', 'start': 155, 'end': 159, 'mesh': 'D012892'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 164, 'end': 175, 'mesh': 'D001058'}, {'text': 'aggressiveness', 'type': 'Disease', 'start': 184, 'end': 198, 'mesh': 'D001523'}, {'text': 'quipazine', 'type': 'Chemical', 'start': 203, 'end': 212, 'mesh': 'D011814'}, {'text': 'head twitches', 'type': 'Disease', 'start': 221, 'end': 234, 'mesh': 'D009069'}, {'text': 'REMD', 'type': 'Disease', 'start': 278, 'end': 282, 'mesh': 'D012892'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 293, 'end': 304, 'mesh': 'D001058'}, {'text': 'aggressiveness', 'type': 'Disease', 'start': 313, 'end': 327, 'mesh': 'D001523'}, {'text': 'REMD', 'type': 'Disease', 'start': 374, 'end': 378, 'mesh': 'D012892'}, {'text': 'REMD', 'type': 'Disease', 'start': 420, 'end': 424, 'mesh': 'D012892'}, {'text': 'quipazine', 'type': 'Chemical', 'start': 426, 'end': 435, 'mesh': 'D011814'}, {'text': 'head twitches', 'type': 'Disease', 'start': 444, 'end': 457, 'mesh': 'D009069'}]"
+958,7161250,Extrapyramidal side effects and oral haloperidol: an analysis of explanatory patient and treatment characteristics.,"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.","[{'text': 'haloperidol', 'type': 'Chemical', 'start': 37, 'end': 48, 'mesh': 'D006220'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 209, 'end': 220, 'mesh': 'D006220'}, {'text': 'parkinsonism', 'type': 'Disease', 'start': 239, 'end': 251, 'mesh': 'D010302'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 282, 'end': 293, 'mesh': 'D006220'}, {'text': 'parkinsonism', 'type': 'Disease', 'start': 507, 'end': 519, 'mesh': 'D010302'}, {'text': 'Akathisia', 'type': 'Disease', 'start': 531, 'end': 540, 'mesh': 'D017109'}, {'text': 'benzodiazepine', 'type': 'Chemical', 'start': 563, 'end': 577, 'mesh': 'D001569'}, {'text': 'lorazepam', 'type': 'Chemical', 'start': 578, 'end': 587, 'mesh': 'D008140'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 782, 'end': 793, 'mesh': 'D006220'}]"
+959,7053705,Hepatic veno-occlusive disease caused by 6-thioguanine.,"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.","[{'text': 'Hepatic veno-occlusive disease', 'type': 'Disease', 'start': 0, 'end': 30, 'mesh': 'D006504'}, {'text': '6-thioguanine', 'type': 'Chemical', 'start': 41, 'end': 54, 'mesh': 'D013866'}, {'text': 'veno-occlusive disease of the liver', 'type': 'Disease', 'start': 78, 'end': 113, 'mesh': 'D006504'}, {'text': 'acute lymphocytic leukemia', 'type': 'Disease', 'start': 150, 'end': 176, 'mesh': 'D054198'}, {'text': '6-thioguanine', 'type': 'Chemical', 'start': 221, 'end': 234, 'mesh': 'D013866'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 396, 'end': 404, 'mesh': 'D005355'}, {'text': 'hepatic veno-occlusive disease', 'type': 'Disease', 'start': 550, 'end': 580, 'mesh': 'D006504'}, {'text': '6-thioguanine', 'type': 'Chemical', 'start': 654, 'end': 667, 'mesh': 'D013866'}]"
+960,6402369,Treatment of ifosfamide-induced urothelial toxicity by oral administration of sodium 2-mercaptoethane sulphonate (MESNA) to patients with inoperable lung cancer.,"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.","[{'text': 'ifosfamide', 'type': 'Chemical', 'start': 13, 'end': 23, 'mesh': 'D007069'}, {'text': 'urothelial toxicity', 'type': 'Disease', 'start': 32, 'end': 51, 'mesh': 'D001745'}, {'text': 'sodium 2-mercaptoethane sulphonate', 'type': 'Chemical', 'start': 78, 'end': 112, 'mesh': 'D015080'}, {'text': 'MESNA', 'type': 'Chemical', 'start': 114, 'end': 119, 'mesh': 'D015080'}, {'text': 'lung cancer', 'type': 'Disease', 'start': 149, 'end': 160, 'mesh': 'D008175'}, {'text': 'thiol', 'type': 'Chemical', 'start': 214, 'end': 219, 'mesh': 'D013438'}, {'text': 'sodium 2-mercaptoethane sulphonate', 'type': 'Chemical', 'start': 229, 'end': 263, 'mesh': 'D015080'}, {'text': 'MESNA', 'type': 'Chemical', 'start': 265, 'end': 270, 'mesh': 'D015080'}, {'text': 'urothelial toxicity', 'type': 'Disease', 'start': 280, 'end': 299, 'mesh': 'D001745'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 311, 'end': 321, 'mesh': 'D007069'}, {'text': 'IF', 'type': 'Chemical', 'start': 323, 'end': 325, 'mesh': 'D007069'}, {'text': 'lung cancer', 'type': 'Disease', 'start': 380, 'end': 391, 'mesh': 'D008175'}, {'text': 'IF', 'type': 'Chemical', 'start': 413, 'end': 415, 'mesh': 'D007069'}, {'text': 'MESNA', 'type': 'Chemical', 'start': 507, 'end': 512, 'mesh': 'D015080'}, {'text': 'IF', 'type': 'Chemical', 'start': 560, 'end': 562, 'mesh': 'D007069'}, {'text': 'IF', 'type': 'Chemical', 'start': 630, 'end': 632, 'mesh': 'D007069'}, {'text': 'haematuria', 'type': 'Disease', 'start': 753, 'end': 763, 'mesh': 'D006417'}, {'text': 'haematuria', 'type': 'Disease', 'start': 789, 'end': 799, 'mesh': 'D006417'}, {'text': 'MESNA', 'type': 'Chemical', 'start': 852, 'end': 857, 'mesh': 'D015080'}, {'text': 'IF', 'type': 'Chemical', 'start': 988, 'end': 990, 'mesh': 'D007069'}, {'text': 'haematuria', 'type': 'Disease', 'start': 1206, 'end': 1216, 'mesh': 'D006417'}, {'text': 'bladder irritation', 'type': 'Disease', 'start': 1236, 'end': 1254, 'mesh': 'D001745'}, {'text': 'cystitis', 'type': 'Disease', 'start': 1256, 'end': 1264, 'mesh': 'D003556'}, {'text': 'pollakisuria', 'type': 'Disease', 'start': 1269, 'end': 1281, 'mesh': 'D014555'}, {'text': 'MESNA', 'type': 'Chemical', 'start': 1334, 'end': 1339, 'mesh': 'D015080'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1437, 'end': 1445, 'mesh': 'D064420'}, {'text': 'MESNA', 'type': 'Chemical', 'start': 1509, 'end': 1514, 'mesh': 'D015080'}, {'text': 'IF', 'type': 'Chemical', 'start': 1592, 'end': 1594, 'mesh': 'D007069'}, {'text': 'MESNA', 'type': 'Chemical', 'start': 1702, 'end': 1707, 'mesh': 'D015080'}]"
+961,3973521,Time course alterations of QTC interval due to hypaque 76.,"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.","[{'text': 'hypaque 76', 'type': 'Chemical', 'start': 47, 'end': 57, 'mesh': 'C027278'}, {'text': 'hypaque 76', 'type': 'Chemical', 'start': 209, 'end': 219, 'mesh': 'C027278'}, {'text': 'QTC prolongation', 'type': 'Disease', 'start': 324, 'end': 340, 'mesh': 'D008133'}, {'text': 'hypotension', 'type': 'Disease', 'start': 405, 'end': 416, 'mesh': 'D007022'}]"
+962,3461217,Production of autochthonous prostate cancer in Lobund-Wistar rats by treatments with N-nitroso-N-methylurea and testosterone.,"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.","[{'text': 'prostate cancer', 'type': 'Disease', 'start': 28, 'end': 43, 'mesh': 'D011471'}, {'text': 'N-nitroso-N-methylurea', 'type': 'Chemical', 'start': 85, 'end': 107, 'mesh': 'D008770'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 112, 'end': 124, 'mesh': 'D013739'}, {'text': 'prostate adenocarcinomas', 'type': 'Disease', 'start': 201, 'end': 225, 'mesh': 'D011471'}, {'text': 'PAs', 'type': 'Disease', 'start': 227, 'end': 230, 'mesh': 'D011471'}, {'text': 'N-nitroso-N-methylurea', 'type': 'Chemical', 'start': 258, 'end': 280, 'mesh': 'D008770'}, {'text': 'testosterone propionate', 'type': 'Chemical', 'start': 301, 'end': 324, 'mesh': 'D043343'}, {'text': 'TP', 'type': 'Chemical', 'start': 327, 'end': 329, 'mesh': 'D043343'}, {'text': 'tumor', 'type': 'Disease', 'start': 362, 'end': 367, 'mesh': 'D009369'}, {'text': 'PA', 'type': 'Disease', 'start': 524, 'end': 526, 'mesh': 'D011471'}, {'text': 'TP', 'type': 'Chemical', 'start': 550, 'end': 552, 'mesh': 'D043343'}, {'text': 'TP', 'type': 'Chemical', 'start': 567, 'end': 569, 'mesh': 'D043343'}, {'text': 'tumor', 'type': 'Disease', 'start': 581, 'end': 586, 'mesh': 'D009369'}, {'text': 'prostate cancer', 'type': 'Disease', 'start': 650, 'end': 665, 'mesh': 'D011471'}]"
+963,2840807,A dystonia-like syndrome after neuropeptide (MSH/ACTH) stimulation of the rat locus ceruleus.,"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.","[{'text': 'dystonia', 'type': 'Disease', 'start': 2, 'end': 10, 'mesh': 'D004421'}, {'text': 'MSH', 'type': 'Chemical', 'start': 45, 'end': 48, 'mesh': 'D009074'}, {'text': 'ACTH', 'type': 'Chemical', 'start': 49, 'end': 53, 'mesh': 'D000324'}, {'text': 'movement disorder', 'type': 'Disease', 'start': 98, 'end': 115, 'mesh': 'D009069'}, {'text': 'dystonia', 'type': 'Disease', 'start': 196, 'end': 204, 'mesh': 'D004421'}, {'text': 'ACTH', 'type': 'Chemical', 'start': 580, 'end': 584, 'mesh': 'D000324'}, {'text': 'depression', 'type': 'Disease', 'start': 788, 'end': 798, 'mesh': 'D003866'}, {'text': 'movement disorder', 'type': 'Disease', 'start': 900, 'end': 917, 'mesh': 'D009069'}]"
+964,2569282,"Dexmedetomidine, acting through central alpha-2 adrenoceptors, prevents opiate-induced muscle rigidity in the rat.","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)","[{'text': 'Dexmedetomidine', 'type': 'Chemical', 'start': 0, 'end': 15, 'mesh': 'D020927'}, {'text': 'muscle rigidity', 'type': 'Disease', 'start': 87, 'end': 102, 'mesh': 'D009127'}, {'text': 'dexmedetomidine', 'type': 'Chemical', 'start': 163, 'end': 178, 'mesh': 'D020927'}, {'text': 'D-MED', 'type': 'Chemical', 'start': 180, 'end': 185, 'mesh': 'D020927'}, {'text': 'muscle flaccidity', 'type': 'Disease', 'start': 210, 'end': 227, 'mesh': 'D009123'}, {'text': 'muscle rigidity', 'type': 'Disease', 'start': 281, 'end': 296, 'mesh': 'D009127'}, {'text': 'rigidity', 'type': 'Disease', 'start': 400, 'end': 408, 'mesh': 'D009127'}, {'text': 'D-MED', 'type': 'Chemical', 'start': 568, 'end': 573, 'mesh': 'D020927'}, {'text': 'muscle rigidity', 'type': 'Disease', 'start': 587, 'end': 602, 'mesh': 'D009127'}, {'text': 'alfentanil', 'type': 'Chemical', 'start': 623, 'end': 633, 'mesh': 'D015760'}, {'text': 'medetomidine', 'type': 'Chemical', 'start': 780, 'end': 792, 'mesh': 'D020926'}, {'text': 'D-MED', 'type': 'Chemical', 'start': 816, 'end': 821, 'mesh': 'D020927'}, {'text': 'D-MED', 'type': 'Chemical', 'start': 844, 'end': 849, 'mesh': 'D020927'}, {'text': 'D-MED', 'type': 'Chemical', 'start': 872, 'end': 877, 'mesh': 'D020927'}, {'text': 'idazoxan', 'type': 'Chemical', 'start': 940, 'end': 948, 'mesh': 'D019329'}, {'text': 'D-MED', 'type': 'Chemical', 'start': 964, 'end': 969, 'mesh': 'D020927'}, {'text': 'DG-5128', 'type': 'Chemical', 'start': 1034, 'end': 1041, 'mesh': 'C032368'}, {'text': 'alfentanil', 'type': 'Chemical', 'start': 1213, 'end': 1223, 'mesh': 'D015760'}, {'text': 'ALF', 'type': 'Chemical', 'start': 1225, 'end': 1228, 'mesh': 'D015760'}, {'text': 'ALF', 'type': 'Chemical', 'start': 1245, 'end': 1248, 'mesh': 'D015760'}, {'text': 'D-MED', 'type': 'Chemical', 'start': 1431, 'end': 1436, 'mesh': 'D020927'}, {'text': 'alfentanil', 'type': 'Chemical', 'start': 1447, 'end': 1457, 'mesh': 'D015760'}, {'text': 'muscle rigidity', 'type': 'Disease', 'start': 1466, 'end': 1481, 'mesh': 'D009127'}, {'text': 'D-MED', 'type': 'Chemical', 'start': 1558, 'end': 1563, 'mesh': 'D020927'}, {'text': 'D-MED', 'type': 'Chemical', 'start': 1682, 'end': 1687, 'mesh': 'D020927'}, {'text': 'akinetic', 'type': 'Disease', 'start': 1710, 'end': 1718, 'mesh': 'D018476'}, {'text': 'startle', 'type': 'Disease', 'start': 1733, 'end': 1740, 'mesh': 'D012021'}]"
+965,2343592,Seizure activity with imipenem therapy: incidence and risk factors.,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.,"[{'text': 'Seizure', 'type': 'Disease', 'start': 0, 'end': 7, 'mesh': 'D012640'}, {'text': 'imipenem', 'type': 'Chemical', 'start': 22, 'end': 30, 'mesh': 'D015378'}, {'text': 'cerebral vascular accident', 'type': 'Disease', 'start': 114, 'end': 140, 'mesh': 'D020521'}, {'text': 'CVA', 'type': 'Disease', 'start': 142, 'end': 145, 'mesh': 'D020521'}, {'text': 'head trauma', 'type': 'Disease', 'start': 150, 'end': 161, 'mesh': 'D006259'}, {'text': 'renal disease', 'type': 'Disease', 'start': 181, 'end': 194, 'mesh': 'D007674'}, {'text': 'seizures', 'type': 'Disease', 'start': 205, 'end': 213, 'mesh': 'D012640'}, {'text': 'imipenem/cilastatin', 'type': 'Chemical', 'start': 247, 'end': 266, 'mesh': 'C044650'}, {'text': 'seizures', 'type': 'Disease', 'start': 306, 'end': 314, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 318, 'end': 325, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 385, 'end': 393, 'mesh': 'D012640'}, {'text': 'phenytoin', 'type': 'Chemical', 'start': 436, 'end': 445, 'mesh': 'D010672'}, {'text': 'beta-lactam', 'type': 'Chemical', 'start': 497, 'end': 508, 'mesh': 'D047090'}, {'text': 'seizure', 'type': 'Disease', 'start': 541, 'end': 548, 'mesh': 'D012640'}]"
+966,2055425,The ability of insulin treatment to reverse or prevent the changes in urinary bladder function caused by streptozotocin-induced diabetes mellitus.,"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.","[{'text': 'streptozotocin', 'type': 'Chemical', 'start': 105, 'end': 119, 'mesh': 'D013311'}, {'text': 'diabetes mellitus', 'type': 'Disease', 'start': 128, 'end': 145, 'mesh': 'D003920'}, {'text': 'streptozotocin', 'type': 'Chemical', 'start': 235, 'end': 249, 'mesh': 'D013311'}, {'text': 'diabetic', 'type': 'Disease', 'start': 250, 'end': 258, 'mesh': 'D003920'}, {'text': 'Diabetes', 'type': 'Disease', 'start': 286, 'end': 294, 'mesh': 'D003920'}, {'text': 'diabetic', 'type': 'Disease', 'start': 619, 'end': 627, 'mesh': 'D003920'}, {'text': 'ATP', 'type': 'Chemical', 'start': 655, 'end': 658, 'mesh': 'D000255'}, {'text': 'bethanechol', 'type': 'Chemical', 'start': 664, 'end': 675, 'mesh': 'D018723'}, {'text': 'Diabetes', 'type': 'Disease', 'start': 680, 'end': 688, 'mesh': 'D003920'}, {'text': 'diabetic', 'type': 'Disease', 'start': 1048, 'end': 1056, 'mesh': 'D003920'}, {'text': 'ATP', 'type': 'Chemical', 'start': 1084, 'end': 1087, 'mesh': 'D000255'}, {'text': 'bethanechol', 'type': 'Chemical', 'start': 1093, 'end': 1104, 'mesh': 'D018723'}, {'text': 'streptozotocin', 'type': 'Chemical', 'start': 1147, 'end': 1161, 'mesh': 'D013311'}, {'text': 'diabetes', 'type': 'Disease', 'start': 1170, 'end': 1178, 'mesh': 'D003920'}]"
+967,1711760,Delayed institution of hypertension during focal cerebral ischemia: effect on brain edema.,"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.","[{'text': 'hypertension', 'type': 'Disease', 'start': 23, 'end': 35, 'mesh': 'D006973'}, {'text': 'cerebral ischemia', 'type': 'Disease', 'start': 49, 'end': 66, 'mesh': 'D002545'}, {'text': 'brain edema', 'type': 'Disease', 'start': 78, 'end': 89, 'mesh': 'D001929'}, {'text': 'hypertension', 'type': 'Disease', 'start': 113, 'end': 125, 'mesh': 'D006973'}, {'text': 'middle cerebral artery occlusion', 'type': 'Disease', 'start': 165, 'end': 197, 'mesh': 'D020244'}, {'text': 'MCAO', 'type': 'Disease', 'start': 199, 'end': 203, 'mesh': 'D020244'}, {'text': 'brain edema', 'type': 'Disease', 'start': 208, 'end': 219, 'mesh': 'D001929'}, {'text': 'isoflurane', 'type': 'Chemical', 'start': 274, 'end': 284, 'mesh': 'D007530'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 325, 'end': 337, 'mesh': 'D006973'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 448, 'end': 460, 'mesh': 'D006973'}, {'text': 'MCAO', 'type': 'Disease', 'start': 532, 'end': 536, 'mesh': 'D020244'}, {'text': 'MCAO', 'type': 'Disease', 'start': 555, 'end': 559, 'mesh': 'D020244'}, {'text': 'ischemia', 'type': 'Disease', 'start': 684, 'end': 692, 'mesh': 'D007511'}, {'text': 'MCAO', 'type': 'Disease', 'start': 705, 'end': 709, 'mesh': 'D020244'}, {'text': 'ischemic', 'type': 'Disease', 'start': 823, 'end': 831, 'mesh': 'D007511'}, {'text': 'neuronal injury', 'type': 'Disease', 'start': 858, 'end': 873, 'mesh': 'D009410'}, {'text': '2,3,5-triphenyltetrazolium', 'type': 'Chemical', 'start': 892, 'end': 918, 'mesh': 'C009591'}, {'text': 'ischemic', 'type': 'Disease', 'start': 936, 'end': 944, 'mesh': 'D007511'}, {'text': 'ischemic', 'type': 'Disease', 'start': 1052, 'end': 1060, 'mesh': 'D007511'}, {'text': 'edema', 'type': 'Disease', 'start': 1107, 'end': 1112, 'mesh': 'D004487'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 1134, 'end': 1146, 'mesh': 'D006973'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 1319, 'end': 1331, 'mesh': 'D006973'}, {'text': 'phenylephrine', 'type': 'Chemical', 'start': 1405, 'end': 1418, 'mesh': 'D010656'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1427, 'end': 1439, 'mesh': 'D006973'}, {'text': 'MCAO', 'type': 'Disease', 'start': 1461, 'end': 1465, 'mesh': 'D020244'}, {'text': 'edema', 'type': 'Disease', 'start': 1485, 'end': 1490, 'mesh': 'D004487'}, {'text': 'ischemic', 'type': 'Disease', 'start': 1498, 'end': 1506, 'mesh': 'D007511'}, {'text': 'edema', 'type': 'Disease', 'start': 1530, 'end': 1535, 'mesh': 'D004487'}, {'text': 'ischemic', 'type': 'Disease', 'start': 1560, 'end': 1568, 'mesh': 'D007511'}, {'text': 'neuronal dysfunction', 'type': 'Disease', 'start': 1626, 'end': 1646, 'mesh': 'D009410'}]"
+968,1595783,Amiodarone pulmonary toxicity.,"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.","[{'text': 'Amiodarone', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D000638'}, {'text': 'pulmonary toxicity', 'type': 'Disease', 'start': 11, 'end': 29, 'mesh': 'D008171'}, {'text': 'Amiodarone', 'type': 'Chemical', 'start': 31, 'end': 41, 'mesh': 'D000638'}, {'text': 'pneumonitis', 'type': 'Disease', 'start': 153, 'end': 164, 'mesh': 'D011014'}, {'text': 'pulmonary toxicity', 'type': 'Disease', 'start': 170, 'end': 188, 'mesh': 'D008171'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 192, 'end': 202, 'mesh': 'D000638'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 393, 'end': 403, 'mesh': 'D000638'}, {'text': 'pulmonary toxicity', 'type': 'Disease', 'start': 412, 'end': 430, 'mesh': 'D008171'}, {'text': 'heart failure', 'type': 'Disease', 'start': 529, 'end': 542, 'mesh': 'D006333'}, {'text': 'infection', 'type': 'Disease', 'start': 544, 'end': 553, 'mesh': 'D007239'}, {'text': 'malignancy', 'type': 'Disease', 'start': 559, 'end': 569, 'mesh': 'D009369'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 591, 'end': 601, 'mesh': 'D000638'}, {'text': 'steroid', 'type': 'Chemical', 'start': 726, 'end': 733, 'mesh': 'D013256'}]"
+969,804391,Light chain proteinuria and cellular mediated immunity in rifampin treated patients with tuberculosis.,"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.","[{'text': 'proteinuria', 'type': 'Disease', 'start': 12, 'end': 23, 'mesh': 'D011507'}, {'text': 'rifampin', 'type': 'Chemical', 'start': 58, 'end': 66, 'mesh': 'D012293'}, {'text': 'tuberculosis', 'type': 'Disease', 'start': 89, 'end': 101, 'mesh': 'D014376'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 115, 'end': 126, 'mesh': 'D011507'}, {'text': 'tuberculosis', 'type': 'Disease', 'start': 148, 'end': 160, 'mesh': 'D014376'}, {'text': 'rifampin', 'type': 'Chemical', 'start': 183, 'end': 191, 'mesh': 'D012293'}, {'text': 'tuberculosis', 'type': 'Disease', 'start': 418, 'end': 430, 'mesh': 'D014376'}, {'text': 'tuberculous', 'type': 'Disease', 'start': 593, 'end': 604, 'mesh': 'D014376'}, {'text': 'rifampin', 'type': 'Chemical', 'start': 702, 'end': 710, 'mesh': 'D012293'}]"
+970,28952,Initial potassium loss and hypokalaemia during chlorthalidone administration in patients with essential hypertension: the influence of dietary sodium restriction.,"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.","[{'text': 'potassium', 'type': 'Chemical', 'start': 8, 'end': 17, 'mesh': 'D011188'}, {'text': 'hypokalaemia', 'type': 'Disease', 'start': 27, 'end': 39, 'mesh': 'D007008'}, {'text': 'chlorthalidone', 'type': 'Chemical', 'start': 47, 'end': 61, 'mesh': 'D002752'}, {'text': 'hypertension', 'type': 'Disease', 'start': 104, 'end': 116, 'mesh': 'D006973'}, {'text': 'sodium', 'type': 'Chemical', 'start': 143, 'end': 149, 'mesh': 'D012964'}, {'text': 'potassium', 'type': 'Chemical', 'start': 190, 'end': 199, 'mesh': 'D011188'}, {'text': 'hypokalaemia', 'type': 'Disease', 'start': 224, 'end': 236, 'mesh': 'D007008'}, {'text': 'hypertension', 'type': 'Disease', 'start': 356, 'end': 368, 'mesh': 'D006973'}, {'text': 'hypokalaemia', 'type': 'Disease', 'start': 383, 'end': 395, 'mesh': 'D007008'}, {'text': 'Chlorthalidone', 'type': 'Chemical', 'start': 433, 'end': 447, 'mesh': 'D002752'}, {'text': 'sodium', 'type': 'Chemical', 'start': 516, 'end': 522, 'mesh': 'D012964'}, {'text': 'sodium', 'type': 'Chemical', 'start': 543, 'end': 549, 'mesh': 'D012964'}, {'text': 'potassium', 'type': 'Chemical', 'start': 615, 'end': 624, 'mesh': 'D011188'}, {'text': 'aldosterone', 'type': 'Chemical', 'start': 708, 'end': 719, 'mesh': 'D000450'}, {'text': 'potassium', 'type': 'Chemical', 'start': 767, 'end': 776, 'mesh': 'D011188'}, {'text': 'sodium', 'type': 'Chemical', 'start': 908, 'end': 914, 'mesh': 'D012964'}, {'text': 'potassium', 'type': 'Chemical', 'start': 938, 'end': 947, 'mesh': 'D011188'}, {'text': 'potassium', 'type': 'Chemical', 'start': 996, 'end': 1005, 'mesh': 'D011188'}, {'text': 'sodium', 'type': 'Chemical', 'start': 1031, 'end': 1037, 'mesh': 'D012964'}, {'text': 'sodium', 'type': 'Chemical', 'start': 1099, 'end': 1105, 'mesh': 'D012964'}, {'text': 'aldosterone', 'type': 'Chemical', 'start': 1168, 'end': 1179, 'mesh': 'D000450'}, {'text': 'sodium', 'type': 'Chemical', 'start': 1199, 'end': 1205, 'mesh': 'D012964'}, {'text': 'aldosterone', 'type': 'Chemical', 'start': 1222, 'end': 1233, 'mesh': 'D000450'}, {'text': 'sodium', 'type': 'Chemical', 'start': 1308, 'end': 1314, 'mesh': 'D012964'}, {'text': 'potassium', 'type': 'Chemical', 'start': 1354, 'end': 1363, 'mesh': 'D011188'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 1419, 'end': 1430, 'mesh': 'D000809'}, {'text': 'aldosterone', 'type': 'Chemical', 'start': 1431, 'end': 1442, 'mesh': 'D000450'}, {'text': 'sodium', 'type': 'Chemical', 'start': 1457, 'end': 1463, 'mesh': 'D012964'}, {'text': 'potassium', 'type': 'Chemical', 'start': 1546, 'end': 1555, 'mesh': 'D011188'}]"
+971,19893084,Dynamic response of blood vessel in acute renal failure.,"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.","[{'text': 'acute renal failure', 'type': 'Disease', 'start': 36, 'end': 55, 'mesh': 'D058186'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 97, 'end': 116, 'mesh': 'D058186'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 128, 'end': 138, 'mesh': 'D005839'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 605, 'end': 615, 'mesh': 'D005839'}, {'text': 'vitamin C', 'type': 'Chemical', 'start': 659, 'end': 668, 'mesh': 'D001205'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 687, 'end': 697, 'mesh': 'D005839'}, {'text': 'urea', 'type': 'Chemical', 'start': 763, 'end': 767, 'mesh': 'D014508'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 772, 'end': 782, 'mesh': 'D003404'}, {'text': 'potassium', 'type': 'Chemical', 'start': 803, 'end': 812, 'mesh': 'D011188'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 904, 'end': 914, 'mesh': 'D005839'}, {'text': 'Vitamin C', 'type': 'Chemical', 'start': 969, 'end': 978, 'mesh': 'D001205'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 1267, 'end': 1277, 'mesh': 'D005839'}, {'text': 'vitamin C', 'type': 'Chemical', 'start': 1320, 'end': 1329, 'mesh': 'D001205'}]"
+972,18513945,The hemodynamics of oxytocin and other vasoactive agents during neuraxial anesthesia for cesarean delivery: findings in six cases.,"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.","[{'text': 'oxytocin', 'type': 'Chemical', 'start': 20, 'end': 28, 'mesh': 'D010121'}, {'text': 'Oxytocin', 'type': 'Chemical', 'start': 131, 'end': 139, 'mesh': 'D010121'}, {'text': 'hypotension', 'type': 'Disease', 'start': 212, 'end': 223, 'mesh': 'D007022'}, {'text': 'hypotension', 'type': 'Disease', 'start': 275, 'end': 286, 'mesh': 'D007022'}, {'text': 'hypotension', 'type': 'Disease', 'start': 509, 'end': 520, 'mesh': 'D007022'}, {'text': 'stroke', 'type': 'Disease', 'start': 568, 'end': 574, 'mesh': 'D020521'}, {'text': 'Oxytocin', 'type': 'Chemical', 'start': 583, 'end': 591, 'mesh': 'D010121'}, {'text': 'hypotension', 'type': 'Disease', 'start': 600, 'end': 611, 'mesh': 'D007022'}, {'text': 'blood loss', 'type': 'Disease', 'start': 666, 'end': 676, 'mesh': 'D006473'}, {'text': 'Hypotension', 'type': 'Disease', 'start': 1049, 'end': 1060, 'mesh': 'D007022'}, {'text': 'oxytocin', 'type': 'Chemical', 'start': 1076, 'end': 1084, 'mesh': 'D010121'}, {'text': 'stroke', 'type': 'Disease', 'start': 1179, 'end': 1185, 'mesh': 'D020521'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1305, 'end': 1316, 'mesh': 'D007022'}]"
+973,18483878,Exaggerated expression of inflammatory mediators in vasoactive intestinal polypeptide knockout (VIP-/-) mice with cyclophosphamide (CYP)-induced cystitis.,"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.","[{'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 114, 'end': 130, 'mesh': 'D003520'}, {'text': 'CYP', 'type': 'Chemical', 'start': 132, 'end': 135, 'mesh': 'D003520'}, {'text': 'cystitis', 'type': 'Disease', 'start': 145, 'end': 153, 'mesh': 'D003556'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 374, 'end': 390, 'mesh': 'D003520'}, {'text': 'CYP', 'type': 'Chemical', 'start': 392, 'end': 395, 'mesh': 'D003520'}, {'text': 'cystitis', 'type': 'Disease', 'start': 405, 'end': 413, 'mesh': 'D003556'}, {'text': 'cystitis', 'type': 'Disease', 'start': 563, 'end': 571, 'mesh': 'D003556'}, {'text': 'CYP', 'type': 'Chemical', 'start': 754, 'end': 757, 'mesh': 'D003520'}, {'text': 'cystitis', 'type': 'Disease', 'start': 766, 'end': 774, 'mesh': 'D003556'}, {'text': 'CYP', 'type': 'Chemical', 'start': 853, 'end': 856, 'mesh': 'D003520'}, {'text': 'CYP', 'type': 'Chemical', 'start': 899, 'end': 902, 'mesh': 'D003520'}, {'text': 'CYP', 'type': 'Chemical', 'start': 969, 'end': 972, 'mesh': 'D003520'}, {'text': 'CYP', 'type': 'Chemical', 'start': 1011, 'end': 1014, 'mesh': 'D003520'}, {'text': 'CYP', 'type': 'Chemical', 'start': 1287, 'end': 1290, 'mesh': 'D003520'}, {'text': 'CYP', 'type': 'Chemical', 'start': 1460, 'end': 1463, 'mesh': 'D003520'}, {'text': 'bladder inflammation', 'type': 'Disease', 'start': 1656, 'end': 1676, 'mesh': 'D001745'}, {'text': 'CYP', 'type': 'Chemical', 'start': 1746, 'end': 1749, 'mesh': 'D003520'}, {'text': 'bladder dysfunction', 'type': 'Disease', 'start': 1801, 'end': 1820, 'mesh': 'D001745'}, {'text': 'bladder inflammation', 'type': 'Disease', 'start': 1843, 'end': 1863, 'mesh': 'D001745'}]"
+974,17923537,Intraocular pressure in patients with uveitis treated with fluocinolone acetonide implants.,"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.","[{'text': 'uveitis', 'type': 'Disease', 'start': 38, 'end': 45, 'mesh': 'D014605'}, {'text': 'fluocinolone acetonide', 'type': 'Chemical', 'start': 59, 'end': 81, 'mesh': 'D005446'}, {'text': 'elevated intraocular pressure', 'type': 'Disease', 'start': 145, 'end': 174, 'mesh': 'D009798'}, {'text': 'uveitis', 'type': 'Disease', 'start': 198, 'end': 205, 'mesh': 'D014605'}, {'text': 'fluocinolone acetonide', 'type': 'Chemical', 'start': 223, 'end': 245, 'mesh': 'D005446'}, {'text': 'FA', 'type': 'Chemical', 'start': 247, 'end': 249, 'mesh': 'D005446'}, {'text': 'FA', 'type': 'Chemical', 'start': 439, 'end': 441, 'mesh': 'D005446'}, {'text': 'hypotony', 'type': 'Disease', 'start': 1123, 'end': 1131, 'mesh': 'D015814'}]"
+975,15096016,Pallidal stimulation: an alternative to pallidotomy?,"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.","[{'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 107, 'end': 126, 'mesh': 'D010300'}, {'text': 'PD', 'type': 'Disease', 'start': 128, 'end': 130, 'mesh': 'D010300'}, {'text': 'PD', 'type': 'Disease', 'start': 271, 'end': 273, 'mesh': 'D010300'}, {'text': 'PD', 'type': 'Disease', 'start': 666, 'end': 668, 'mesh': 'D010300'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 678, 'end': 689, 'mesh': 'D004409'}, {'text': 'rigidity', 'type': 'Disease', 'start': 730, 'end': 738, 'mesh': 'D009127'}, {'text': 'bradykinesia', 'type': 'Disease', 'start': 740, 'end': 752, 'mesh': 'D018476'}, {'text': 'bradykinesia', 'type': 'Disease', 'start': 809, 'end': 821, 'mesh': 'D018476'}, {'text': 'rigidity', 'type': 'Disease', 'start': 826, 'end': 834, 'mesh': 'D009127'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 901, 'end': 909, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 918, 'end': 929, 'mesh': 'D004409'}, {'text': 'hyper- or dyskinetic', 'type': 'Disease', 'start': 980, 'end': 1000, 'mesh': 'D006948|D004409'}]"
+976,12734532,Case report: Dexatrim (Phenylpropanolamine) as a cause of myocardial infarction.,"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.","[{'text': 'Dexatrim', 'type': 'Chemical', 'start': 13, 'end': 21, 'mesh': 'D010665'}, {'text': 'Phenylpropanolamine', 'type': 'Chemical', 'start': 23, 'end': 42, 'mesh': 'D010665'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 58, 'end': 79, 'mesh': 'D009203'}, {'text': 'Phenylpropanolamine', 'type': 'Chemical', 'start': 81, 'end': 100, 'mesh': 'D010665'}, {'text': 'PPA', 'type': 'Chemical', 'start': 102, 'end': 105, 'mesh': 'D010665'}, {'text': 'amine', 'type': 'Chemical', 'start': 124, 'end': 129, 'mesh': 'D000588'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 245, 'end': 257, 'mesh': 'D006973'}, {'text': 'PPA', 'type': 'Chemical', 'start': 350, 'end': 353, 'mesh': 'D010665'}, {'text': 'myocardial injury', 'type': 'Disease', 'start': 359, 'end': 376, 'mesh': 'D009202'}, {'text': 'overdose', 'type': 'Disease', 'start': 394, 'end': 402, 'mesh': 'D062787'}, {'text': 'Dexatrim', 'type': 'Chemical', 'start': 449, 'end': 457, 'mesh': 'D010665'}, {'text': 'PPA', 'type': 'Chemical', 'start': 459, 'end': 462, 'mesh': 'D010665'}, {'text': 'myocardial injury', 'type': 'Disease', 'start': 472, 'end': 489, 'mesh': 'D009202'}, {'text': 'PPA', 'type': 'Chemical', 'start': 609, 'end': 612, 'mesh': 'D010665'}, {'text': 'myocardial injury', 'type': 'Disease', 'start': 621, 'end': 638, 'mesh': 'D009202'}, {'text': 'PPA', 'type': 'Chemical', 'start': 768, 'end': 771, 'mesh': 'D010665'}]"
+977,12013711,"Risperidone-associated, benign transient visual disturbances in schizophrenic patients with a past history of LSD abuse.","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.","[{'text': 'Risperidone', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D018967'}, {'text': 'visual disturbances', 'type': 'Disease', 'start': 41, 'end': 60, 'mesh': 'D010468'}, {'text': 'schizophrenic', 'type': 'Disease', 'start': 64, 'end': 77, 'mesh': 'D012559'}, {'text': 'LSD', 'type': 'Chemical', 'start': 110, 'end': 113, 'mesh': 'D008238'}, {'text': 'schizophrenic', 'type': 'Disease', 'start': 125, 'end': 138, 'mesh': 'D012559'}, {'text': 'LSD', 'type': 'Chemical', 'start': 176, 'end': 179, 'mesh': 'D008238'}, {'text': 'EPS', 'type': 'Disease', 'start': 219, 'end': 222, 'mesh': 'D001480'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 283, 'end': 294, 'mesh': 'D018967'}, {'text': 'visual disturbances', 'type': 'Disease', 'start': 343, 'end': 362, 'mesh': 'D010468'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 421, 'end': 432, 'mesh': 'D018967'}, {'text': 'visual disturbances', 'type': 'Disease', 'start': 457, 'end': 476, 'mesh': 'D010468'}, {'text': 'LSD', 'type': 'Chemical', 'start': 533, 'end': 536, 'mesh': 'D008238'}, {'text': 'Risperidone', 'type': 'Chemical', 'start': 550, 'end': 561, 'mesh': 'D018967'}, {'text': 'visual disturbances', 'type': 'Disease', 'start': 599, 'end': 618, 'mesh': 'D010468'}, {'text': 'visual disturbances', 'type': 'Disease', 'start': 703, 'end': 722, 'mesh': 'D010468'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 854, 'end': 865, 'mesh': 'D018967'}]"
+978,11861791,Activation of poly(ADP-ribose) polymerase contributes to development of doxorubicin-induced heart failure.,"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.","[{'text': 'poly(ADP-ribose)', 'type': 'Chemical', 'start': 14, 'end': 30, 'mesh': 'D011064'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 72, 'end': 83, 'mesh': 'D004317'}, {'text': 'heart failure', 'type': 'Disease', 'start': 92, 'end': 105, 'mesh': 'D006333'}, {'text': 'poly(ADP-ribose)', 'type': 'Chemical', 'start': 140, 'end': 156, 'mesh': 'D011064'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 379, 'end': 393, 'mesh': 'D066126'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 397, 'end': 408, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 410, 'end': 413, 'mesh': 'D004317'}, {'text': 'anthracycline', 'type': 'Chemical', 'start': 440, 'end': 453, 'mesh': 'D018943'}, {'text': 'DOX', 'type': 'Chemical', 'start': 538, 'end': 541, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 550, 'end': 564, 'mesh': 'D066126'}, {'text': 'PJ34', 'type': 'Chemical', 'start': 702, 'end': 706, 'mesh': 'C434926'}, {'text': 'cardiac dysfunction', 'type': 'Disease', 'start': 766, 'end': 785, 'mesh': 'D006331'}, {'text': 'DOX', 'type': 'Chemical', 'start': 797, 'end': 800, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 862, 'end': 865, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 898, 'end': 901, 'mesh': 'D004317'}, {'text': 'PJ34', 'type': 'Chemical', 'start': 1105, 'end': 1109, 'mesh': 'C434926'}, {'text': 'PJ34', 'type': 'Chemical', 'start': 1139, 'end': 1143, 'mesh': 'C434926'}, {'text': 'cardiac dysfunction', 'type': 'Disease', 'start': 1167, 'end': 1186, 'mesh': 'D006331'}, {'text': 'PJ34', 'type': 'Chemical', 'start': 1242, 'end': 1246, 'mesh': 'C434926'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1273, 'end': 1276, 'mesh': 'D004317'}, {'text': 'lactate', 'type': 'Chemical', 'start': 1307, 'end': 1314, 'mesh': 'D019344'}, {'text': 'creatine', 'type': 'Chemical', 'start': 1333, 'end': 1341, 'mesh': 'D003401'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1452, 'end': 1466, 'mesh': 'D066126'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1470, 'end': 1473, 'mesh': 'D004317'}, {'text': 'cardiac complications', 'type': 'Disease', 'start': 1554, 'end': 1575, 'mesh': 'D005117'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1596, 'end': 1599, 'mesh': 'D004317'}]"
+979,11302406,Fluconazole-induced torsade de pointes.,"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.","[{'text': 'Fluconazole', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D015725'}, {'text': 'torsade de pointes', 'type': 'Disease', 'start': 20, 'end': 38, 'mesh': 'D016171'}, {'text': 'fluconazole', 'type': 'Chemical', 'start': 72, 'end': 83, 'mesh': 'D015725'}, {'text': 'torsade de pointes', 'type': 'Disease', 'start': 95, 'end': 113, 'mesh': 'D016171'}, {'text': 'TDP', 'type': 'Disease', 'start': 115, 'end': 118, 'mesh': 'D016171'}, {'text': 'fluconazole', 'type': 'Chemical', 'start': 132, 'end': 143, 'mesh': 'D015725'}, {'text': 'TDP', 'type': 'Disease', 'start': 162, 'end': 165, 'mesh': 'D016171'}, {'text': 'TDP', 'type': 'Disease', 'start': 273, 'end': 276, 'mesh': 'D016171'}, {'text': 'fluconazole', 'type': 'Chemical', 'start': 310, 'end': 321, 'mesh': 'D015725'}, {'text': 'TDP', 'type': 'Disease', 'start': 364, 'end': 367, 'mesh': 'D016171'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 379, 'end': 402, 'mesh': 'D003324'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 404, 'end': 418, 'mesh': 'D009202'}, {'text': 'congestive heart failure', 'type': 'Disease', 'start': 420, 'end': 444, 'mesh': 'D006333'}, {'text': 'fluconazole', 'type': 'Chemical', 'start': 535, 'end': 546, 'mesh': 'D015725'}, {'text': 'TDP', 'type': 'Disease', 'start': 551, 'end': 554, 'mesh': 'D016171'}, {'text': 'TDP', 'type': 'Disease', 'start': 560, 'end': 563, 'mesh': 'D016171'}, {'text': 'fluconazole', 'type': 'Chemical', 'start': 578, 'end': 589, 'mesh': 'D015725'}, {'text': 'premature ventricular contractions', 'type': 'Disease', 'start': 647, 'end': 681, 'mesh': 'D018879'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 699, 'end': 722, 'mesh': 'D017180'}, {'text': 'NSVT', 'type': 'Disease', 'start': 724, 'end': 728, 'mesh': 'D017180'}, {'text': 'fluconazole', 'type': 'Chemical', 'start': 868, 'end': 879, 'mesh': 'D015725'}, {'text': 'TDP', 'type': 'Disease', 'start': 903, 'end': 906, 'mesh': 'D016171'}, {'text': 'depression', 'type': 'Disease', 'start': 934, 'end': 944, 'mesh': 'D003866'}, {'text': 'potassium', 'type': 'Chemical', 'start': 985, 'end': 994, 'mesh': 'D011188'}, {'text': 'QT prolongation', 'type': 'Disease', 'start': 1079, 'end': 1094, 'mesh': 'D008133'}, {'text': 'TDP', 'type': 'Disease', 'start': 1098, 'end': 1101, 'mesh': 'D016171'}, {'text': 'NSVT', 'type': 'Disease', 'start': 1132, 'end': 1136, 'mesh': 'D017180'}, {'text': 'premature ventricular contractions', 'type': 'Disease', 'start': 1141, 'end': 1175, 'mesh': 'D018879'}, {'text': 'fluconazole', 'type': 'Chemical', 'start': 1262, 'end': 1273, 'mesh': 'D015725'}, {'text': 'fluconazole', 'type': 'Chemical', 'start': 1336, 'end': 1347, 'mesh': 'D015725'}, {'text': 'prolongation of the QT interval', 'type': 'Disease', 'start': 1378, 'end': 1409, 'mesh': 'D008133'}, {'text': 'TDP', 'type': 'Disease', 'start': 1422, 'end': 1425, 'mesh': 'D016171'}, {'text': 'fluconazole', 'type': 'Chemical', 'start': 1489, 'end': 1500, 'mesh': 'D015725'}, {'text': 'ventricular arrhythmias', 'type': 'Disease', 'start': 1549, 'end': 1572, 'mesh': 'D001145'}]"
+980,11058428,High-dose methylprednisolone may do more harm for spinal cord injury.,"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.","[{'text': 'methylprednisolone', 'type': 'Chemical', 'start': 10, 'end': 28, 'mesh': 'D008775'}, {'text': 'spinal cord injury', 'type': 'Disease', 'start': 50, 'end': 68, 'mesh': 'D013119'}, {'text': 'Spinal Cord Injury', 'type': 'Disease', 'start': 100, 'end': 118, 'mesh': 'D013119'}, {'text': 'methylprednisolone', 'type': 'Chemical', 'start': 147, 'end': 165, 'mesh': 'D008775'}, {'text': 'spinal cord injury', 'type': 'Disease', 'start': 208, 'end': 226, 'mesh': 'D013119'}, {'text': 'corticosteroid', 'type': 'Chemical', 'start': 299, 'end': 313, 'mesh': 'D000305'}, {'text': 'myopathy', 'type': 'Disease', 'start': 314, 'end': 322, 'mesh': 'D009135'}, {'text': 'methylprednisolone', 'type': 'Chemical', 'start': 338, 'end': 356, 'mesh': 'D008775'}, {'text': 'methylprednisolone', 'type': 'Chemical', 'start': 382, 'end': 400, 'mesh': 'D008775'}, {'text': 'steroids', 'type': 'Chemical', 'start': 452, 'end': 460, 'mesh': 'D013256'}, {'text': 'damage to the muscle', 'type': 'Disease', 'start': 565, 'end': 585, 'mesh': 'D009135'}, {'text': 'spinal cord injury', 'type': 'Disease', 'start': 589, 'end': 607, 'mesh': 'D013119'}, {'text': 'steroid', 'type': 'Chemical', 'start': 627, 'end': 634, 'mesh': 'D013256'}, {'text': 'myopathy', 'type': 'Disease', 'start': 635, 'end': 643, 'mesh': 'D009135'}, {'text': 'steroid', 'type': 'Chemical', 'start': 780, 'end': 787, 'mesh': 'D013256'}, {'text': 'myopathy', 'type': 'Disease', 'start': 788, 'end': 796, 'mesh': 'D009135'}, {'text': 'methylprednisolone', 'type': 'Chemical', 'start': 829, 'end': 847, 'mesh': 'D008775'}, {'text': 'spinal cord injury', 'type': 'Disease', 'start': 862, 'end': 880, 'mesh': 'D013119'}, {'text': 'methylprednisolone', 'type': 'Chemical', 'start': 966, 'end': 984, 'mesh': 'D008775'}, {'text': 'corticosteroid', 'type': 'Chemical', 'start': 1023, 'end': 1037, 'mesh': 'D000305'}, {'text': 'myopathy', 'type': 'Disease', 'start': 1038, 'end': 1046, 'mesh': 'D009135'}]"
+981,11022397,Probing peripheral and central cholinergic system responses.,"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.","[{'text': ""Alzheimer's disease"", 'type': 'Disease', 'start': 250, 'end': 269, 'mesh': 'D000544'}, {'text': 'tropicamide', 'type': 'Chemical', 'start': 419, 'end': 430, 'mesh': 'D014331'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 508, 'end': 519, 'mesh': 'D010862'}, {'text': 'Scopolamine', 'type': 'Chemical', 'start': 521, 'end': 532, 'mesh': 'D012601'}, {'text': 'tropicamide', 'type': 'Chemical', 'start': 929, 'end': 940, 'mesh': 'D014331'}, {'text': 'tropicamide', 'type': 'Chemical', 'start': 1034, 'end': 1045, 'mesh': 'D014331'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1144, 'end': 1155, 'mesh': 'D010862'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 1300, 'end': 1311, 'mesh': 'D012601'}, {'text': 'tropicamide', 'type': 'Chemical', 'start': 1535, 'end': 1546, 'mesh': 'D014331'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1551, 'end': 1562, 'mesh': 'D010862'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 1564, 'end': 1575, 'mesh': 'D012601'}, {'text': 'impairment in word recall', 'type': 'Disease', 'start': 1584, 'end': 1609, 'mesh': 'D008569'}, {'text': 'tropicamide', 'type': 'Chemical', 'start': 1718, 'end': 1729, 'mesh': 'D014331'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1806, 'end': 1817, 'mesh': 'D010862'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 2007, 'end': 2018, 'mesh': 'D012601'}, {'text': 'impairment in word recall', 'type': 'Disease', 'start': 2027, 'end': 2052, 'mesh': 'D008569'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 2167, 'end': 2178, 'mesh': 'D010862'}, {'text': 'tropicamide', 'type': 'Chemical', 'start': 2202, 'end': 2213, 'mesh': 'D014331'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 2221, 'end': 2232, 'mesh': 'D010862'}]"
+982,10692744,Acetazolamide-induced Gerstmann syndrome.,"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.","[{'text': 'Acetazolamide', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'D000086'}, {'text': 'Gerstmann syndrome', 'type': 'Disease', 'start': 22, 'end': 40, 'mesh': 'D005862'}, {'text': 'confusion', 'type': 'Disease', 'start': 48, 'end': 57, 'mesh': 'D003221'}, {'text': 'acetazolamide', 'type': 'Chemical', 'start': 69, 'end': 82, 'mesh': 'D000086'}, {'text': 'renal impairment', 'type': 'Disease', 'start': 138, 'end': 154, 'mesh': 'D007674'}, {'text': 'acetazolamide', 'type': 'Chemical', 'start': 176, 'end': 189, 'mesh': 'D000086'}, {'text': 'Gerstmann syndrome', 'type': 'Disease', 'start': 198, 'end': 216, 'mesh': 'D005862'}]"
+983,10565806,Hypomania-like syndrome induced by olanzapine.,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.,"[{'text': 'Hypomania', 'type': 'Disease', 'start': 0, 'end': 9, 'mesh': 'D001714'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 35, 'end': 45, 'mesh': 'C076029'}, {'text': 'psychotic disorder', 'type': 'Disease', 'start': 120, 'end': 138, 'mesh': 'D011618'}, {'text': 'hypomania', 'type': 'Disease', 'start': 162, 'end': 171, 'mesh': 'D001714'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 206, 'end': 216, 'mesh': 'C076029'}]"
+984,9061311,Neutrophil superoxide and hydrogen peroxide production in patients with acute liver failure.,"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.","[{'text': 'superoxide', 'type': 'Chemical', 'start': 11, 'end': 21, 'mesh': 'D013481'}, {'text': 'hydrogen peroxide', 'type': 'Chemical', 'start': 26, 'end': 43, 'mesh': 'D006861'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 72, 'end': 91, 'mesh': 'D017114'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 104, 'end': 114, 'mesh': 'D013481'}, {'text': 'hydrogen peroxide', 'type': 'Chemical', 'start': 119, 'end': 136, 'mesh': 'D006861'}, {'text': 'bacterial infections', 'type': 'Disease', 'start': 191, 'end': 211, 'mesh': 'D001424'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 229, 'end': 248, 'mesh': 'D017114'}, {'text': 'ALF', 'type': 'Disease', 'start': 250, 'end': 253, 'mesh': 'D017114'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 278, 'end': 284, 'mesh': 'D010100'}, {'text': 'ALF', 'type': 'Disease', 'start': 321, 'end': 324, 'mesh': 'D017114'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 332, 'end': 343, 'mesh': 'D000082'}, {'text': 'overdose', 'type': 'Disease', 'start': 344, 'end': 352, 'mesh': 'D062787'}, {'text': 'ALF', 'type': 'Disease', 'start': 419, 'end': 422, 'mesh': 'D017114'}, {'text': 'ALF', 'type': 'Disease', 'start': 506, 'end': 509, 'mesh': 'D017114'}, {'text': 'Superoxide', 'type': 'Chemical', 'start': 528, 'end': 538, 'mesh': 'D013481'}, {'text': 'hydrogen peroxide', 'type': 'Chemical', 'start': 543, 'end': 560, 'mesh': 'D006861'}, {'text': 'ALF', 'type': 'Disease', 'start': 575, 'end': 578, 'mesh': 'D017114'}, {'text': 'ALF', 'type': 'Disease', 'start': 630, 'end': 633, 'mesh': 'D017114'}, {'text': 'Superoxide', 'type': 'Chemical', 'start': 796, 'end': 806, 'mesh': 'D013481'}, {'text': 'hydrogen peroxide', 'type': 'Chemical', 'start': 811, 'end': 828, 'mesh': 'D006861'}, {'text': 'formyl-methionyl-leucyl-phenylalanine', 'type': 'Chemical', 'start': 871, 'end': 908, 'mesh': 'D009240'}, {'text': 'fMLP', 'type': 'Chemical', 'start': 910, 'end': 914, 'mesh': 'D009240'}, {'text': 'ALF', 'type': 'Disease', 'start': 934, 'end': 937, 'mesh': 'D017114'}, {'text': 'ALF', 'type': 'Disease', 'start': 1054, 'end': 1057, 'mesh': 'D017114'}, {'text': 'ALF', 'type': 'Disease', 'start': 1161, 'end': 1164, 'mesh': 'D017114'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 1172, 'end': 1183, 'mesh': 'D000082'}, {'text': 'overdose', 'type': 'Disease', 'start': 1184, 'end': 1192, 'mesh': 'D062787'}]"
+985,8617710,Absence of effect of sertraline on time-based sensitization of cognitive impairment with haloperidol.,"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.","[{'text': 'sertraline', 'type': 'Chemical', 'start': 21, 'end': 31, 'mesh': 'D020280'}, {'text': 'cognitive impairment', 'type': 'Disease', 'start': 63, 'end': 83, 'mesh': 'D003072'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 89, 'end': 100, 'mesh': 'D006220'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 183, 'end': 194, 'mesh': 'D006220'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 205, 'end': 216, 'mesh': 'D006220'}, {'text': 'sertraline', 'type': 'Chemical', 'start': 222, 'end': 232, 'mesh': 'D020280'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 351, 'end': 362, 'mesh': 'D006220'}, {'text': 'sertraline', 'type': 'Chemical', 'start': 447, 'end': 457, 'mesh': 'D020280'}, {'text': 'sertraline', 'type': 'Chemical', 'start': 502, 'end': 512, 'mesh': 'D020280'}, {'text': 'Impairment of cognitive function', 'type': 'Disease', 'start': 781, 'end': 813, 'mesh': 'D003072'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 864, 'end': 875, 'mesh': 'D006220'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 945, 'end': 956, 'mesh': 'D006220'}, {'text': 'sertraline', 'type': 'Chemical', 'start': 1147, 'end': 1157, 'mesh': 'D020280'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1197, 'end': 1208, 'mesh': 'D006220'}, {'text': 'sertraline', 'type': 'Chemical', 'start': 1293, 'end': 1303, 'mesh': 'D020280'}, {'text': 'sertraline', 'type': 'Chemical', 'start': 1470, 'end': 1480, 'mesh': 'D020280'}, {'text': 'Haloperidol', 'type': 'Chemical', 'start': 1522, 'end': 1533, 'mesh': 'D006220'}, {'text': 'cognitive impairment', 'type': 'Disease', 'start': 1562, 'end': 1582, 'mesh': 'D003072'}, {'text': 'sertraline', 'type': 'Chemical', 'start': 1620, 'end': 1630, 'mesh': 'D020280'}]"
+986,8494478,Ciprofloxacin-induced nephrotoxicity in patients with cancer.,"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.","[{'text': 'Ciprofloxacin', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'D002939'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 22, 'end': 36, 'mesh': 'D007674'}, {'text': 'cancer', 'type': 'Disease', 'start': 54, 'end': 60, 'mesh': 'D009369'}, {'text': 'Nephrotoxicity', 'type': 'Disease', 'start': 62, 'end': 76, 'mesh': 'D007674'}, {'text': 'ciprofloxacin', 'type': 'Chemical', 'start': 93, 'end': 106, 'mesh': 'D002939'}, {'text': 'cancer', 'type': 'Disease', 'start': 139, 'end': 145, 'mesh': 'D009369'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 160, 'end': 179, 'mesh': 'D058186'}, {'text': 'ciprofloxacin', 'type': 'Chemical', 'start': 209, 'end': 222, 'mesh': 'D002939'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 335, 'end': 345, 'mesh': 'D003404'}, {'text': 'interstitial nephritis', 'type': 'Disease', 'start': 463, 'end': 485, 'mesh': 'D009395'}, {'text': 'ciprofloxacin', 'type': 'Chemical', 'start': 771, 'end': 784, 'mesh': 'D002939'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 793, 'end': 812, 'mesh': 'D058186'}]"
+987,8475949,Case report: pentamidine and polymorphic ventricular tachycardia revisited.,"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.","[{'text': 'pentamidine', 'type': 'Chemical', 'start': 13, 'end': 24, 'mesh': 'D010419'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 41, 'end': 64, 'mesh': 'D017180'}, {'text': 'Pentamidine isethionate', 'type': 'Chemical', 'start': 76, 'end': 99, 'mesh': 'D010419'}, {'text': 'ventricular tachyarrhythmias', 'type': 'Disease', 'start': 125, 'end': 153, 'mesh': 'D017180'}, {'text': 'torsade de pointes', 'type': 'Disease', 'start': 165, 'end': 183, 'mesh': 'D016171'}, {'text': 'Pentamidine', 'type': 'Chemical', 'start': 277, 'end': 288, 'mesh': 'D010419'}, {'text': 'torsade de pointes', 'type': 'Disease', 'start': 297, 'end': 315, 'mesh': 'D016171'}, {'text': 'magnesium', 'type': 'Chemical', 'start': 340, 'end': 349, 'mesh': 'D008274'}, {'text': 'hypomagnesemia', 'type': 'Disease', 'start': 361, 'end': 375, 'mesh': 'C537153'}, {'text': 'Torsade de pointes', 'type': 'Disease', 'start': 412, 'end': 430, 'mesh': 'D016171'}, {'text': 'pentamidine', 'type': 'Chemical', 'start': 486, 'end': 497, 'mesh': 'D010419'}, {'text': 'pentamidine', 'type': 'Chemical', 'start': 549, 'end': 560, 'mesh': 'D010419'}, {'text': 'Torsade de pointes', 'type': 'Disease', 'start': 576, 'end': 594, 'mesh': 'D016171'}, {'text': 'pentamidine', 'type': 'Chemical', 'start': 669, 'end': 680, 'mesh': 'D010419'}, {'text': 'QTc interval prolongation', 'type': 'Disease', 'start': 687, 'end': 712, 'mesh': 'D008133'}, {'text': 'magnesium', 'type': 'Chemical', 'start': 732, 'end': 741, 'mesh': 'D008274'}]"
+988,7710775,"Time dependence of plasma malondialdehyde, oxypurines, and nucleosides during incomplete cerebral ischemia in the rat.","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)","[{'text': 'malondialdehyde', 'type': 'Chemical', 'start': 26, 'end': 41, 'mesh': 'D008315'}, {'text': 'oxypurines', 'type': 'Chemical', 'start': 43, 'end': 53, 'mesh': '-1'}, {'text': 'nucleosides', 'type': 'Chemical', 'start': 59, 'end': 70, 'mesh': 'D009705'}, {'text': 'cerebral ischemia', 'type': 'Disease', 'start': 89, 'end': 106, 'mesh': 'D002545'}, {'text': 'cerebral ischemia', 'type': 'Disease', 'start': 130, 'end': 147, 'mesh': 'D002545'}, {'text': 'ischemia', 'type': 'Disease', 'start': 339, 'end': 347, 'mesh': 'D007511'}, {'text': 'ischemia', 'type': 'Disease', 'start': 385, 'end': 393, 'mesh': 'D007511'}, {'text': 'malondialdehyde', 'type': 'Chemical', 'start': 526, 'end': 541, 'mesh': 'D008315'}, {'text': 'oxypurines', 'type': 'Chemical', 'start': 543, 'end': 553, 'mesh': '-1'}, {'text': 'nucleosides', 'type': 'Chemical', 'start': 559, 'end': 570, 'mesh': 'D009705'}, {'text': 'ischemia', 'type': 'Disease', 'start': 579, 'end': 587, 'mesh': 'D007511'}, {'text': 'oxypurines', 'type': 'Chemical', 'start': 625, 'end': 635, 'mesh': '-1'}, {'text': 'nucleosides', 'type': 'Chemical', 'start': 640, 'end': 651, 'mesh': 'D009705'}, {'text': 'malondialdehyde', 'type': 'Chemical', 'start': 673, 'end': 688, 'mesh': 'D008315'}, {'text': 'ischemia', 'type': 'Disease', 'start': 802, 'end': 810, 'mesh': 'D007511'}, {'text': 'malondialdehyde', 'type': 'Chemical', 'start': 934, 'end': 949, 'mesh': 'D008315'}, {'text': 'acetylsalicylate', 'type': 'Chemical', 'start': 1101, 'end': 1117, 'mesh': 'D001241'}, {'text': 'ischemia', 'type': 'Disease', 'start': 1151, 'end': 1159, 'mesh': 'D007511'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 1211, 'end': 1222, 'mesh': 'D007022'}, {'text': 'nitroprusside', 'type': 'Chemical', 'start': 1228, 'end': 1241, 'mesh': 'D009599'}, {'text': 'ischemia', 'type': 'Disease', 'start': 1301, 'end': 1309, 'mesh': 'D007511'}, {'text': 'malondialdehyde', 'type': 'Chemical', 'start': 1341, 'end': 1356, 'mesh': 'D008315'}, {'text': 'malondialdehyde', 'type': 'Chemical', 'start': 1435, 'end': 1450, 'mesh': 'D008315'}, {'text': 'oxypurines', 'type': 'Chemical', 'start': 1452, 'end': 1462, 'mesh': '-1'}, {'text': 'nucleosides', 'type': 'Chemical', 'start': 1468, 'end': 1479, 'mesh': 'D009705'}, {'text': 'ischemic', 'type': 'Disease', 'start': 1578, 'end': 1586, 'mesh': 'D007511'}]"
+989,7650771,Cholinergic toxicity resulting from ocular instillation of echothiophate iodide eye drops.,"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.","[{'text': 'toxicity', 'type': 'Disease', 'start': 12, 'end': 20, 'mesh': 'D064420'}, {'text': 'echothiophate iodide', 'type': 'Chemical', 'start': 59, 'end': 79, 'mesh': 'D004456'}, {'text': 'echothiophate iodide', 'type': 'Chemical', 'start': 157, 'end': 177, 'mesh': 'D004456'}, {'text': 'muscle weakness', 'type': 'Disease', 'start': 220, 'end': 235, 'mesh': 'D018908'}, {'text': 'myasthenia gravis', 'type': 'Disease', 'start': 277, 'end': 294, 'mesh': 'D009157'}]"
+990,7565311,Acute renal failure in high dose carboplatin chemotherapy.,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.,"[{'text': 'Acute renal failure', 'type': 'Disease', 'start': 0, 'end': 19, 'mesh': 'D058186'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 33, 'end': 44, 'mesh': 'D016190'}, {'text': 'Carboplatin', 'type': 'Chemical', 'start': 59, 'end': 70, 'mesh': 'D016190'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 98, 'end': 117, 'mesh': 'D058186'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 232, 'end': 243, 'mesh': 'D016190'}, {'text': 'embryonal rhabdomyosarcoma', 'type': 'Disease', 'start': 273, 'end': 299, 'mesh': 'D018233'}, {'text': 'Acute renal failure', 'type': 'Disease', 'start': 301, 'end': 320, 'mesh': 'D058186'}]"
+991,7421734,Endometrial carcinoma after Hodgkin disease in childhood.,"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.","[{'text': 'Endometrial carcinoma', 'type': 'Disease', 'start': 0, 'end': 21, 'mesh': 'D016889'}, {'text': 'Hodgkin disease', 'type': 'Disease', 'start': 28, 'end': 43, 'mesh': 'D006689'}, {'text': 'endometrial carcinoma', 'type': 'Disease', 'start': 99, 'end': 120, 'mesh': 'D016889'}, {'text': 'Hodgkin disease', 'type': 'Disease', 'start': 127, 'end': 142, 'mesh': 'D006689'}, {'text': 'ovarian failure', 'type': 'Disease', 'start': 165, 'end': 180, 'mesh': 'D010049'}, {'text': 'Hodgkin disease', 'type': 'Disease', 'start': 230, 'end': 245, 'mesh': 'D006689'}, {'text': 'estrogens', 'type': 'Chemical', 'start': 270, 'end': 279, 'mesh': 'D004967'}, {'text': 'endometrial cancer', 'type': 'Disease', 'start': 326, 'end': 344, 'mesh': 'D016889'}, {'text': 'estrogens', 'type': 'Chemical', 'start': 393, 'end': 402, 'mesh': 'D004967'}, {'text': 'ovarian failure', 'type': 'Disease', 'start': 407, 'end': 422, 'mesh': 'D010049'}, {'text': 'cancer', 'type': 'Disease', 'start': 429, 'end': 435, 'mesh': 'D009369'}, {'text': 'endometrial carcinoma', 'type': 'Disease', 'start': 476, 'end': 497, 'mesh': 'D016889'}]"
+992,6732043,Induction of the obstructive sleep apnea syndrome in a woman by exogenous androgen administration.,"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.","[{'text': 'obstructive sleep apnea syndrome', 'type': 'Disease', 'start': 17, 'end': 49, 'mesh': 'D020181'}, {'text': 'androgen', 'type': 'Chemical', 'start': 74, 'end': 82, 'mesh': 'D000728'}, {'text': 'syndrome of obstructive sleep apnea', 'type': 'Disease', 'start': 266, 'end': 301, 'mesh': 'D020181'}, {'text': 'androgens', 'type': 'Chemical', 'start': 337, 'end': 346, 'mesh': 'D000728'}, {'text': 'androgens', 'type': 'Chemical', 'start': 357, 'end': 366, 'mesh': 'D000728'}, {'text': 'androgen', 'type': 'Chemical', 'start': 509, 'end': 517, 'mesh': 'D000728'}, {'text': 'obstructive sleep apnea', 'type': 'Disease', 'start': 539, 'end': 562, 'mesh': 'D020181'}, {'text': 'androgens', 'type': 'Chemical', 'start': 647, 'end': 656, 'mesh': 'D000728'}, {'text': 'sleep apnea', 'type': 'Disease', 'start': 680, 'end': 691, 'mesh': 'D012891'}, {'text': 'androgens', 'type': 'Chemical', 'start': 797, 'end': 806, 'mesh': 'D000728'}, {'text': 'obstructive sleep apnea syndrome', 'type': 'Disease', 'start': 961, 'end': 993, 'mesh': 'D020181'}, {'text': 'androgen', 'type': 'Chemical', 'start': 1039, 'end': 1047, 'mesh': 'D000728'}]"
+993,6454943,Effect of captopril on pre-existing and aminonucleoside-induced proteinuria in spontaneously hypertensive rats.,"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.","[{'text': 'captopril', 'type': 'Chemical', 'start': 10, 'end': 19, 'mesh': 'D002216'}, {'text': 'aminonucleoside', 'type': 'Chemical', 'start': 40, 'end': 55, 'mesh': 'D011692'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 64, 'end': 75, 'mesh': 'D011507'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 93, 'end': 105, 'mesh': 'D006973'}, {'text': 'Proteinuria', 'type': 'Disease', 'start': 112, 'end': 123, 'mesh': 'D011507'}, {'text': 'captopril', 'type': 'Chemical', 'start': 144, 'end': 153, 'mesh': 'D002216'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 167, 'end': 179, 'mesh': 'D006973'}, {'text': 'renal abnormality', 'type': 'Disease', 'start': 230, 'end': 247, 'mesh': 'D007674'}, {'text': 'captopril', 'type': 'Chemical', 'start': 253, 'end': 262, 'mesh': 'D002216'}, {'text': 'captopril', 'type': 'Chemical', 'start': 307, 'end': 316, 'mesh': 'D002216'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 362, 'end': 373, 'mesh': 'D011507'}, {'text': 'captopril', 'type': 'Chemical', 'start': 401, 'end': 410, 'mesh': 'D002216'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 479, 'end': 490, 'mesh': 'D011507'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 502, 'end': 527, 'mesh': 'D011692'}, {'text': 'Captopril', 'type': 'Chemical', 'start': 536, 'end': 545, 'mesh': 'D002216'}, {'text': 'sodium', 'type': 'Chemical', 'start': 641, 'end': 647, 'mesh': 'D012964'}, {'text': 'potassium', 'type': 'Chemical', 'start': 652, 'end': 661, 'mesh': 'D011188'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 674, 'end': 684, 'mesh': 'D003404'}, {'text': 'ketone', 'type': 'Chemical', 'start': 750, 'end': 756, 'mesh': 'D007659'}, {'text': 'captopril', 'type': 'Chemical', 'start': 858, 'end': 867, 'mesh': 'D002216'}]"
+994,6153967,Epileptogenic properties of enflurane and their clinical interpretation.,"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.","[{'text': 'enflurane', 'type': 'Chemical', 'start': 28, 'end': 37, 'mesh': 'D004737'}, {'text': 'enflurane', 'type': 'Chemical', 'start': 130, 'end': 139, 'mesh': 'D004737'}, {'text': 'enflurane', 'type': 'Chemical', 'start': 181, 'end': 190, 'mesh': 'D004737'}, {'text': 'seizures', 'type': 'Disease', 'start': 268, 'end': 276, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 301, 'end': 309, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 464, 'end': 472, 'mesh': 'D012640'}, {'text': 'Epileptic', 'type': 'Disease', 'start': 501, 'end': 510, 'mesh': 'D004827'}, {'text': 'enflurane', 'type': 'Chemical', 'start': 544, 'end': 553, 'mesh': 'D004737'}, {'text': 'seizure', 'type': 'Disease', 'start': 603, 'end': 610, 'mesh': 'D012640'}, {'text': 'enflurane', 'type': 'Chemical', 'start': 639, 'end': 648, 'mesh': 'D004737'}, {'text': 'enflurane', 'type': 'Chemical', 'start': 746, 'end': 755, 'mesh': 'D004737'}, {'text': 'epileptic', 'type': 'Disease', 'start': 804, 'end': 813, 'mesh': 'D004827'}]"
+995,3183120,Reversible cerebral lesions associated with tiazofurin usage: MR demonstration.,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.,"[{'text': 'cerebral lesions', 'type': 'Disease', 'start': 11, 'end': 27, 'mesh': 'D001927'}, {'text': 'tiazofurin', 'type': 'Chemical', 'start': 44, 'end': 54, 'mesh': 'C033706'}, {'text': 'Tiazofurin', 'type': 'Chemical', 'start': 80, 'end': 90, 'mesh': 'C033706'}, {'text': 'cerebral abnormalities', 'type': 'Disease', 'start': 254, 'end': 276, 'mesh': 'D001927'}]"
+996,3120485,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.,"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.","[{'text': 'diazepam', 'type': 'Chemical', 'start': 14, 'end': 22, 'mesh': 'D003975'}, {'text': 'Ro15-1788', 'type': 'Chemical', 'start': 51, 'end': 60, 'mesh': 'D005442'}, {'text': 'Ro15-1788', 'type': 'Chemical', 'start': 240, 'end': 249, 'mesh': 'D005442'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 277, 'end': 285, 'mesh': 'D003975'}, {'text': 'Ro15-1788', 'type': 'Chemical', 'start': 396, 'end': 405, 'mesh': 'D005442'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 446, 'end': 454, 'mesh': 'D003975'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 509, 'end': 517, 'mesh': 'D003975'}, {'text': 'Ro15-1788', 'type': 'Chemical', 'start': 537, 'end': 546, 'mesh': 'D005442'}, {'text': 'amnesia', 'type': 'Disease', 'start': 721, 'end': 728, 'mesh': 'D000647'}, {'text': 'amnesia', 'type': 'Disease', 'start': 899, 'end': 906, 'mesh': 'D000647'}, {'text': 'Ro15-1788', 'type': 'Chemical', 'start': 928, 'end': 937, 'mesh': 'D005442'}]"
+997,2886572,Enhanced stimulus-induced neurotransmitter overflow in epinephrine-induced hypertensive rats is not mediated by prejunctional beta-adrenoceptor activation.,"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.","[{'text': 'epinephrine', 'type': 'Chemical', 'start': 55, 'end': 66, 'mesh': 'D004837'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 75, 'end': 87, 'mesh': 'D006973'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 203, 'end': 214, 'mesh': 'D004837'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 371, 'end': 382, 'mesh': 'D004837'}, {'text': 'catecholamine', 'type': 'Chemical', 'start': 403, 'end': 416, 'mesh': 'D002395'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 496, 'end': 510, 'mesh': 'D009638'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 526, 'end': 537, 'mesh': 'D004837'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 581, 'end': 592, 'mesh': 'D004837'}, {'text': 'catecholamine', 'type': 'Chemical', 'start': 604, 'end': 617, 'mesh': 'D002395'}, {'text': 'catecholamine', 'type': 'Chemical', 'start': 660, 'end': 673, 'mesh': 'D002395'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 686, 'end': 697, 'mesh': 'D004837'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 708, 'end': 722, 'mesh': 'D009638'}, {'text': 'catecholamine', 'type': 'Chemical', 'start': 777, 'end': 790, 'mesh': 'D002395'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 911, 'end': 922, 'mesh': 'D004837'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 992, 'end': 1006, 'mesh': 'D009638'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 1011, 'end': 1022, 'mesh': 'D004837'}, {'text': 'Propranolol', 'type': 'Chemical', 'start': 1194, 'end': 1205, 'mesh': 'D011433'}, {'text': 'Phentolamine', 'type': 'Chemical', 'start': 1266, 'end': 1278, 'mesh': 'D010646'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 1384, 'end': 1395, 'mesh': 'D004837'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 1434, 'end': 1445, 'mesh': 'D004837'}, {'text': 'phentolamine', 'type': 'Chemical', 'start': 1731, 'end': 1743, 'mesh': 'D010646'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 1861, 'end': 1872, 'mesh': 'D004837'}]"
+998,1079693,Ocular manifestations of juvenile rheumatoid arthritis.,"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.","[{'text': 'juvenile rheumatoid arthritis', 'type': 'Disease', 'start': 25, 'end': 54, 'mesh': 'D001171'}, {'text': 'juvenile rheumatoid arthritis', 'type': 'Disease', 'start': 81, 'end': 110, 'mesh': 'D001171'}, {'text': 'iridocyclitis', 'type': 'Disease', 'start': 186, 'end': 199, 'mesh': 'D015863'}, {'text': 'Iridocyclitis', 'type': 'Disease', 'start': 201, 'end': 214, 'mesh': 'D015863'}, {'text': 'arthritis', 'type': 'Disease', 'start': 333, 'end': 342, 'mesh': 'D001168'}, {'text': 'uveitis', 'type': 'Disease', 'start': 383, 'end': 390, 'mesh': 'D014605'}, {'text': 'uveitis', 'type': 'Disease', 'start': 501, 'end': 508, 'mesh': 'D014605'}, {'text': 'uveitis', 'type': 'Disease', 'start': 559, 'end': 566, 'mesh': 'D014605'}, {'text': 'uveitis', 'type': 'Disease', 'start': 601, 'end': 608, 'mesh': 'D014605'}, {'text': 'uveitis', 'type': 'Disease', 'start': 667, 'end': 674, 'mesh': 'D014605'}, {'text': 'ocular pain', 'type': 'Disease', 'start': 740, 'end': 751, 'mesh': 'D058447'}, {'text': 'decreased visual acuity', 'type': 'Disease', 'start': 753, 'end': 776, 'mesh': 'D014786'}, {'text': 'photophobia', 'type': 'Disease', 'start': 781, 'end': 792, 'mesh': 'D020795'}, {'text': 'uveitis', 'type': 'Disease', 'start': 893, 'end': 900, 'mesh': 'D014605'}, {'text': 'corticosteroids', 'type': 'Chemical', 'start': 977, 'end': 992, 'mesh': 'D000305'}, {'text': 'uveitis', 'type': 'Disease', 'start': 1103, 'end': 1110, 'mesh': 'D014605'}, {'text': 'Cataract', 'type': 'Disease', 'start': 1137, 'end': 1145, 'mesh': 'D002386'}, {'text': 'band keratopathy', 'type': 'Disease', 'start': 1150, 'end': 1166, 'mesh': 'C562399'}, {'text': 'chloroquine', 'type': 'Chemical', 'start': 1231, 'end': 1242, 'mesh': 'D002738'}, {'text': 'hydroxychloroquine', 'type': 'Chemical', 'start': 1246, 'end': 1264, 'mesh': 'D006886'}, {'text': 'chorioretinopathy', 'type': 'Disease', 'start': 1312, 'end': 1329, 'mesh': 'D012164'}, {'text': 'corticosteroids', 'type': 'Chemical', 'start': 1385, 'end': 1400, 'mesh': 'D000305'}, {'text': 'cataracts', 'type': 'Disease', 'start': 1477, 'end': 1486, 'mesh': 'D002386'}, {'text': 'keratoconjunctivitis', 'type': 'Disease', 'start': 1506, 'end': 1526, 'mesh': 'D007637'}, {'text': 'uveitis', 'type': 'Disease', 'start': 1559, 'end': 1566, 'mesh': 'D014605'}, {'text': 'uveitis', 'type': 'Disease', 'start': 1596, 'end': 1603, 'mesh': 'D014605'}, {'text': 'cataracts', 'type': 'Disease', 'start': 1660, 'end': 1669, 'mesh': 'D002386'}, {'text': 'band keratopathy', 'type': 'Disease', 'start': 1671, 'end': 1687, 'mesh': 'C562399'}, {'text': 'glaucoma', 'type': 'Disease', 'start': 1693, 'end': 1701, 'mesh': 'D005901'}]"
+999,803783,Water intoxication associated with oxytocin administration during saline-induced abortion.,"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.","[{'text': 'Water intoxication', 'type': 'Disease', 'start': 0, 'end': 18, 'mesh': 'D014869'}, {'text': 'oxytocin', 'type': 'Chemical', 'start': 35, 'end': 43, 'mesh': 'D010121'}, {'text': 'abortion', 'type': 'Disease', 'start': 81, 'end': 89, 'mesh': 'D000031'}, {'text': 'water intoxication', 'type': 'Disease', 'start': 105, 'end': 123, 'mesh': 'D014869'}, {'text': 'oxytocin', 'type': 'Chemical', 'start': 143, 'end': 151, 'mesh': 'D010121'}, {'text': 'abortions', 'type': 'Disease', 'start': 189, 'end': 198, 'mesh': 'D000031'}, {'text': 'water intoxication', 'type': 'Disease', 'start': 231, 'end': 249, 'mesh': 'D014869'}, {'text': 'Oxytocin', 'type': 'Chemical', 'start': 289, 'end': 297, 'mesh': 'D010121'}, {'text': 'abortions', 'type': 'Disease', 'start': 341, 'end': 350, 'mesh': 'D000031'}, {'text': 'water intoxication', 'type': 'Disease', 'start': 473, 'end': 491, 'mesh': 'D014869'}, {'text': 'asthenia', 'type': 'Disease', 'start': 576, 'end': 584, 'mesh': 'D001247'}, {'text': 'irritability', 'type': 'Disease', 'start': 595, 'end': 607, 'mesh': 'D001523'}, {'text': 'headaches', 'type': 'Disease', 'start': 612, 'end': 621, 'mesh': 'D006261'}, {'text': 'oxytocin', 'type': 'Chemical', 'start': 627, 'end': 635, 'mesh': 'D010121'}, {'text': 'lactate', 'type': 'Chemical', 'start': 668, 'end': 675, 'mesh': 'D019344'}, {'text': 'lactate', 'type': 'Chemical', 'start': 704, 'end': 711, 'mesh': 'D019344'}, {'text': 'dextrose', 'type': 'Chemical', 'start': 729, 'end': 737, 'mesh': 'D005947'}, {'text': 'oxytocin', 'type': 'Chemical', 'start': 806, 'end': 814, 'mesh': 'D010121'}, {'text': 'oxytocin', 'type': 'Chemical', 'start': 915, 'end': 923, 'mesh': 'D010121'}, {'text': 'oxytocin', 'type': 'Chemical', 'start': 1017, 'end': 1025, 'mesh': 'D010121'}]"
+1000,8701013,Famotidine-associated delirium. A series of six cases.,"Famotidine is a histamine H2-receptor antagonist used in inpatient settings for prevention of stress ulcers and is showing increasing popularity because of its low cost. Although all of the currently available H2-receptor antagonists have shown the propensity to cause delirium, only two previously reported cases have been associated with famotidine. The authors report on six cases of famotidine-associated delirium in hospitalized patients who cleared completely upon removal of famotidine. The pharmacokinetics of famotidine are reviewed, with no change in its metabolism in the elderly population seen. The implications of using famotidine in elderly persons are discussed.","[{'text': 'Famotidine', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D015738'}, {'text': 'delirium', 'type': 'Disease', 'start': 22, 'end': 30, 'mesh': 'D003693'}, {'text': 'Famotidine', 'type': 'Chemical', 'start': 55, 'end': 65, 'mesh': 'D015738'}, {'text': 'ulcers', 'type': 'Disease', 'start': 156, 'end': 162, 'mesh': 'D014456'}, {'text': 'delirium', 'type': 'Disease', 'start': 324, 'end': 332, 'mesh': 'D003693'}, {'text': 'famotidine', 'type': 'Chemical', 'start': 395, 'end': 405, 'mesh': 'D015738'}, {'text': 'famotidine', 'type': 'Chemical', 'start': 442, 'end': 452, 'mesh': 'D015738'}, {'text': 'delirium', 'type': 'Disease', 'start': 464, 'end': 472, 'mesh': 'D003693'}, {'text': 'famotidine', 'type': 'Chemical', 'start': 537, 'end': 547, 'mesh': 'D015738'}, {'text': 'famotidine', 'type': 'Chemical', 'start': 573, 'end': 583, 'mesh': 'D015738'}, {'text': 'famotidine', 'type': 'Chemical', 'start': 689, 'end': 699, 'mesh': 'D015738'}]"
+1001,439781,Indomethacin induced hypotension in sodium and volume depleted rats.,"After a single oral dose of 4 mg/kg indomethacin (IDM) to sodium and volume depleted rats plasma renin activity (PRA) and systolic blood pressure fell significantly within four hours. In sodium repleted animals indomethacin did not change systolic blood pressure (BP) although plasma renin activity was decreased. Thus, indomethacin by inhibition of prostaglandin synthesis may diminish the blood pressure maintaining effect of the stimulated renin-angiotensin system in sodium and volume depletion.","[{'text': 'Indomethacin', 'type': 'Chemical', 'start': 0, 'end': 12, 'mesh': 'D007213'}, {'text': 'hypotension', 'type': 'Disease', 'start': 21, 'end': 32, 'mesh': 'D007022'}, {'text': 'sodium', 'type': 'Chemical', 'start': 36, 'end': 42, 'mesh': 'D012964'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 105, 'end': 117, 'mesh': 'D007213'}, {'text': 'IDM', 'type': 'Chemical', 'start': 119, 'end': 122, 'mesh': 'D007213'}, {'text': 'sodium', 'type': 'Chemical', 'start': 127, 'end': 133, 'mesh': 'D012964'}, {'text': 'sodium', 'type': 'Chemical', 'start': 256, 'end': 262, 'mesh': 'D012964'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 280, 'end': 292, 'mesh': 'D007213'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 389, 'end': 401, 'mesh': 'D007213'}, {'text': 'prostaglandin', 'type': 'Chemical', 'start': 419, 'end': 432, 'mesh': 'D011453'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 518, 'end': 529, 'mesh': 'D000809'}, {'text': 'sodium', 'type': 'Chemical', 'start': 540, 'end': 546, 'mesh': 'D012964'}]"
+1002,22836123,Late-onset scleroderma renal crisis induced by tacrolimus and prednisolone: a case report.,"Scleroderma renal crisis (SRC) is a rare complication of systemic sclerosis (SSc) but can be severe enough to require temporary or permanent renal replacement therapy. Moderate to high dose corticosteroid use is recognized as a major risk factor for SRC. Furthermore, there have been reports of thrombotic microangiopathy precipitated by cyclosporine in patients with SSc. In this article, we report a patient with SRC induced by tacrolimus and corticosteroids. The aim of this work is to call attention to the risk of tacrolimus use in patients with SSc.","[{'text': 'scleroderma renal crisis', 'type': 'Disease', 'start': 11, 'end': 35, 'mesh': 'D007674'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 47, 'end': 57, 'mesh': 'D016559'}, {'text': 'prednisolone', 'type': 'Chemical', 'start': 62, 'end': 74, 'mesh': 'D011239'}, {'text': 'Scleroderma renal crisis', 'type': 'Disease', 'start': 91, 'end': 115, 'mesh': 'D007674'}, {'text': 'SRC', 'type': 'Disease', 'start': 117, 'end': 120, 'mesh': 'D007674'}, {'text': 'systemic sclerosis', 'type': 'Disease', 'start': 148, 'end': 166, 'mesh': 'D012595'}, {'text': 'SSc', 'type': 'Disease', 'start': 168, 'end': 171, 'mesh': 'D012595'}, {'text': 'corticosteroid', 'type': 'Chemical', 'start': 281, 'end': 295, 'mesh': 'D000305'}, {'text': 'SRC', 'type': 'Disease', 'start': 341, 'end': 344, 'mesh': 'D007674'}, {'text': 'thrombotic microangiopathy', 'type': 'Disease', 'start': 386, 'end': 412, 'mesh': 'D057049'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 429, 'end': 441, 'mesh': 'D016572'}, {'text': 'SSc', 'type': 'Disease', 'start': 459, 'end': 462, 'mesh': 'D012595'}, {'text': 'SRC', 'type': 'Disease', 'start': 506, 'end': 509, 'mesh': 'D007674'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 521, 'end': 531, 'mesh': 'D016559'}, {'text': 'corticosteroids', 'type': 'Chemical', 'start': 536, 'end': 551, 'mesh': 'D000305'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 610, 'end': 620, 'mesh': 'D016559'}, {'text': 'SSc', 'type': 'Disease', 'start': 642, 'end': 645, 'mesh': 'D012595'}]"
+1003,23433219,The risk and associated factors of methamphetamine psychosis in methamphetamine-dependent patients in Malaysia.,"OBJECTIVE: The objective of this study was to determine the risk of lifetime and current methamphetamine-induced psychosis in patients with methamphetamine dependence. The association between psychiatric co-morbidity and methamphetamine-induced psychosis was also studied. METHODS: This was a cross-sectional study conducted concurrently at a teaching hospital and a drug rehabilitation center in Malaysia. Patients with the diagnosis of methamphetamine based on DSM-IV were interviewed using the Mini International Neuropsychiatric Interview (M.I.N.I.) for methamphetamine-induced psychosis and other Axis I psychiatric disorders. The information on sociodemographic background and drug use history was obtained from interview or medical records. RESULTS: Of 292 subjects, 47.9% of the subjects had a past history of psychotic symptoms and 13.0% of the patients were having current psychotic symptoms. Co-morbid major depressive disorder (OR=7.18, 95 CI=2.612-19.708), bipolar disorder (OR=13.807, 95 CI=5.194-36.706), antisocial personality disorder (OR=12.619, 95 CI=6.702-23.759) and heavy methamphetamine uses were significantly associated with lifetime methamphetamine-induced psychosis after adjusted for other factors. Major depressive disorder (OR=2.870, CI=1.154-7.142) and antisocial personality disorder (OR=3.299, 95 CI=1.375-7.914) were the only factors associated with current psychosis. CONCLUSION: There was a high risk of psychosis in patients with methamphetamine dependence. It was associated with co-morbid affective disorder, antisocial personality, and heavy methamphetamine use. It is recommended that all cases of methamphetamine dependence should be screened for psychotic symptoms.","[{'text': 'methamphetamine', 'type': 'Chemical', 'start': 35, 'end': 50, 'mesh': 'D008694'}, {'text': 'psychosis', 'type': 'Disease', 'start': 51, 'end': 60, 'mesh': 'D011605'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 64, 'end': 79, 'mesh': 'D008694'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 201, 'end': 216, 'mesh': 'D008694'}, {'text': 'psychosis', 'type': 'Disease', 'start': 225, 'end': 234, 'mesh': 'D011605'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 252, 'end': 267, 'mesh': 'D008694'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 333, 'end': 348, 'mesh': 'D008694'}, {'text': 'psychosis', 'type': 'Disease', 'start': 357, 'end': 366, 'mesh': 'D011605'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 550, 'end': 565, 'mesh': 'D008694'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 670, 'end': 685, 'mesh': 'D008694'}, {'text': 'psychosis', 'type': 'Disease', 'start': 694, 'end': 703, 'mesh': 'D011605'}, {'text': 'psychiatric disorders', 'type': 'Disease', 'start': 721, 'end': 742, 'mesh': 'D001523'}, {'text': 'psychotic symptoms', 'type': 'Disease', 'start': 930, 'end': 948, 'mesh': 'D011605'}, {'text': 'psychotic symptoms', 'type': 'Disease', 'start': 995, 'end': 1013, 'mesh': 'D011605'}, {'text': 'depressive disorder', 'type': 'Disease', 'start': 1031, 'end': 1050, 'mesh': 'D003866'}, {'text': 'bipolar disorder', 'type': 'Disease', 'start': 1082, 'end': 1098, 'mesh': 'D001714'}, {'text': 'antisocial personality disorder', 'type': 'Disease', 'start': 1132, 'end': 1163, 'mesh': 'D000987'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 1206, 'end': 1221, 'mesh': 'D008694'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 1271, 'end': 1286, 'mesh': 'D008694'}, {'text': 'psychosis', 'type': 'Disease', 'start': 1295, 'end': 1304, 'mesh': 'D011605'}, {'text': 'Major depressive disorder', 'type': 'Disease', 'start': 1339, 'end': 1364, 'mesh': 'D003865'}, {'text': 'antisocial personality disorder', 'type': 'Disease', 'start': 1396, 'end': 1427, 'mesh': 'D000987'}, {'text': 'psychosis', 'type': 'Disease', 'start': 1504, 'end': 1513, 'mesh': 'D011605'}, {'text': 'psychosis', 'type': 'Disease', 'start': 1552, 'end': 1561, 'mesh': 'D011605'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 1579, 'end': 1594, 'mesh': 'D008694'}, {'text': 'affective disorder', 'type': 'Disease', 'start': 1640, 'end': 1658, 'mesh': 'D019964'}, {'text': 'antisocial personality', 'type': 'Disease', 'start': 1660, 'end': 1682, 'mesh': 'D000987'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 1694, 'end': 1709, 'mesh': 'D008694'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 1751, 'end': 1766, 'mesh': 'D008694'}, {'text': 'psychotic symptoms', 'type': 'Disease', 'start': 1801, 'end': 1819, 'mesh': 'D011605'}]"
+1004,23535177,Cerebellar sensory processing alterations impact motor cortical plasticity in Parkinson's disease: clues from dyskinetic patients.,"The plasticity of primary motor cortex (M1) in patients with Parkinson's disease (PD) and levodopa-induced dyskinesias (LIDs) is severely impaired. We recently reported in young healthy subjects that inhibitory cerebellar stimulation enhanced the sensorimotor plasticity of M1 that was induced by paired associative stimulation (PAS). This study demonstrates that the deficient sensorimotor M1 plasticity in 16 patients with LIDs could be reinstated by a single session of real inhibitory cerebellar stimulation but not sham stimulation. This was evident only when a sensory component was involved in the induction of plasticity, indicating that cerebellar sensory processing function is involved in the resurgence of M1 plasticity. The benefit of inhibitory cerebellar stimulation on LIDs is known. To explore whether this benefit is linked to the restoration of sensorimotor plasticity of M1, we conducted an additional study looking at changes in LIDs and PAS-induced plasticity after 10 sessions of either bilateral, real inhibitory cerebellar stimulation or sham stimulation. Only real and not sham stimulation had an antidyskinetic effect and it was paralleled by a resurgence in the sensorimotor plasticity of M1. These results suggest that alterations in cerebellar sensory processing function, occurring secondary to abnormal basal ganglia signals reaching it, may be an important element contributing to the maladaptive sensorimotor plasticity of M1 and the emergence of abnormal involuntary movements.","[{'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 78, 'end': 97, 'mesh': 'D010300'}, {'text': 'dyskinetic', 'type': 'Disease', 'start': 110, 'end': 120, 'mesh': 'D004409'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 192, 'end': 211, 'mesh': 'D010300'}, {'text': 'PD', 'type': 'Disease', 'start': 213, 'end': 215, 'mesh': 'D010300'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 221, 'end': 229, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 238, 'end': 249, 'mesh': 'D004409'}, {'text': 'LIDs', 'type': 'Disease', 'start': 251, 'end': 255, 'mesh': 'D004409'}, {'text': 'LIDs', 'type': 'Disease', 'start': 556, 'end': 560, 'mesh': 'D004409'}, {'text': 'LIDs', 'type': 'Disease', 'start': 916, 'end': 920, 'mesh': 'D004409'}, {'text': 'LIDs', 'type': 'Disease', 'start': 1081, 'end': 1085, 'mesh': 'D004409'}, {'text': 'abnormal involuntary movements', 'type': 'Disease', 'start': 1612, 'end': 1642, 'mesh': 'D004409'}]"
+1005,23666265,The function of P2X3 receptor and NK1 receptor antagonists on cyclophosphamide-induced cystitis in rats.,"PURPOSE: The purpose of the study is to explore the function of P2X3 and NK1 receptors antagonists on cyclophosphamide (CYP)-induced cystitis in rats. METHODS: Sixty female Sprague-Dawley (SD) rats were randomly divided into three groups. The rats in the control group were intraperitoneally (i.p.) injected with 0.9% saline (4 ml/kg); the rats in the model group were i.p. injected with CYP (150 mg/kg); and the rats in the intervention group were i.p. injected with CYP with subsequently perfusion of bladder with P2X3 and NK1 receptors' antagonists, Suramin and GR 82334. Spontaneous pain behaviors following the administration of CYP were observed. Urodynamic parameters, bladder pressure-volume curve, maximum voiding pressure (MVP), and maximum cystometric capacity (MCC), were recorded. Pathological changes in bladder tissue were observed. Immunofluorescence was used to detect the expression of P2X3 and NK1 receptors in bladder. RESULTS: Cyclophosphamide treatment increased the spontaneous pain behaviors scores. The incidence of bladder instability during urine storage period of model group was significantly higher than intervention group (X(2) = 7.619, P = 0.007) and control group (X(2) = 13.755, P = 0.000). MCC in the model group was lower than the control and intervention groups (P < 0.01). Histological changes evident in model and intervention groups rats' bladder included edema, vasodilation, and infiltration of inflammatory cells. In model group, the expression of P2X3 receptor increased in urothelium and suburothelium, and NK1 receptor increased in suburothelium, while the expression of them in intervention group was lower. CONCLUSIONS: In CYP-induced cystitis, the expression of P2X3 and NK1 receptors increased in urothelium and/or suburothelium. Perfusion of bladder with P2X3 and NK1 receptors antagonists ameliorated the bladder function.","[{'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 62, 'end': 78, 'mesh': 'D003520'}, {'text': 'cystitis', 'type': 'Disease', 'start': 87, 'end': 95, 'mesh': 'D003556'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 207, 'end': 223, 'mesh': 'D003520'}, {'text': 'CYP', 'type': 'Chemical', 'start': 225, 'end': 228, 'mesh': 'D003520'}, {'text': 'cystitis', 'type': 'Disease', 'start': 238, 'end': 246, 'mesh': 'D003556'}, {'text': 'CYP', 'type': 'Chemical', 'start': 493, 'end': 496, 'mesh': 'D003520'}, {'text': 'CYP', 'type': 'Chemical', 'start': 573, 'end': 576, 'mesh': 'D003520'}, {'text': 'Suramin', 'type': 'Chemical', 'start': 658, 'end': 665, 'mesh': 'D013498'}, {'text': 'GR 82334', 'type': 'Chemical', 'start': 670, 'end': 678, 'mesh': 'C079014'}, {'text': 'pain', 'type': 'Disease', 'start': 692, 'end': 696, 'mesh': 'D010146'}, {'text': 'CYP', 'type': 'Chemical', 'start': 739, 'end': 742, 'mesh': 'D003520'}, {'text': 'Cyclophosphamide', 'type': 'Chemical', 'start': 1053, 'end': 1069, 'mesh': 'D003520'}, {'text': 'pain', 'type': 'Disease', 'start': 1106, 'end': 1110, 'mesh': 'D010146'}, {'text': 'edema', 'type': 'Disease', 'start': 1501, 'end': 1506, 'mesh': 'D004487'}, {'text': 'CYP', 'type': 'Chemical', 'start': 1776, 'end': 1779, 'mesh': 'D003520'}, {'text': 'cystitis', 'type': 'Disease', 'start': 1788, 'end': 1796, 'mesh': 'D003556'}]"
+1006,23846525,Acute hepatitis associated with clopidogrel: a case report and review of the literature.,"Drug-induced hepatotoxicity is a common cause of acute hepatitis, and the recognition of the responsible drug may be difficult. We describe a case of clopidogrel-related acute hepatitis. The diagnosis is strongly suggested by an accurate medical history and liver biopsy. Reports about cases of hepatotoxicity due to clopidogrel are increasing in the last few years, after the increased use of this drug. In conclusion, we believe that physicians should carefully consider the risk of drug-induced hepatic injury when clopidogrel is prescribed.","[{'text': 'hepatitis', 'type': 'Disease', 'start': 6, 'end': 15, 'mesh': 'D056486'}, {'text': 'clopidogrel', 'type': 'Chemical', 'start': 32, 'end': 43, 'mesh': 'C055162'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 102, 'end': 116, 'mesh': 'D056486'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 144, 'end': 153, 'mesh': 'D056486'}, {'text': 'clopidogrel', 'type': 'Chemical', 'start': 239, 'end': 250, 'mesh': 'C055162'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 265, 'end': 274, 'mesh': 'D056486'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 384, 'end': 398, 'mesh': 'D056486'}, {'text': 'clopidogrel', 'type': 'Chemical', 'start': 406, 'end': 417, 'mesh': 'C055162'}, {'text': 'hepatic injury', 'type': 'Disease', 'start': 587, 'end': 601, 'mesh': 'D056486'}, {'text': 'clopidogrel', 'type': 'Chemical', 'start': 607, 'end': 618, 'mesh': 'C055162'}]"
+1007,23864035,Bortezomib and dexamethasone as salvage therapy in patients with relapsed/refractory multiple myeloma: analysis of long-term clinical outcomes.,"Bortezomib (bort)-dexamethasone (dex) is an effective therapy for relapsed/refractory (R/R) multiple myeloma (MM). This retrospective study investigated the combination of bort (1.3 mg/m(2) on days 1, 4, 8, and 11 every 3 weeks) and dex (20 mg on the day of and the day after bort) as salvage treatment in 85 patients with R/R MM after prior autologous stem cell transplantation or conventional chemotherapy. The median number of prior lines of therapy was 2. Eighty-seven percent of the patients had received immunomodulatory drugs included in some line of therapy before bort-dex. The median number of bort-dex cycles was 6, up to a maximum of 12 cycles. On an intention-to-treat basis, 55 % of the patients achieved at least partial response, including 19 % CR and 35 % achieved at least very good partial response. Median durations of response, time to next therapy and treatment-free interval were 8, 11.2, and 5.1 months, respectively. The most relevant adverse event was peripheral neuropathy, which occurred in 78 % of the patients (grade II, 38 %; grade III, 21 %) and led to treatment discontinuation in 6 %. With a median follow up of 22 months, median time to progression, progression-free survival (PFS) and overall survival (OS) were 8.9, 8.7, and 22 months, respectively. Prolonged PFS and OS were observed in patients achieving CR and receiving bort-dex a single line of prior therapy. Bort-dex was an effective salvage treatment for MM patients, particularly for those in first relapse.","[{'text': 'Bortezomib', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'C400082'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 15, 'end': 28, 'mesh': 'D003907'}, {'text': 'multiple myeloma', 'type': 'Disease', 'start': 85, 'end': 101, 'mesh': 'D009101'}, {'text': 'Bortezomib', 'type': 'Chemical', 'start': 144, 'end': 154, 'mesh': 'C400082'}, {'text': 'bort', 'type': 'Chemical', 'start': 156, 'end': 160, 'mesh': 'C400082'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 162, 'end': 175, 'mesh': 'D003907'}, {'text': 'dex', 'type': 'Chemical', 'start': 177, 'end': 180, 'mesh': 'D003907'}, {'text': 'multiple myeloma', 'type': 'Disease', 'start': 236, 'end': 252, 'mesh': 'D009101'}, {'text': 'MM', 'type': 'Disease', 'start': 254, 'end': 256, 'mesh': 'D009101'}, {'text': 'bort', 'type': 'Chemical', 'start': 316, 'end': 320, 'mesh': 'C400082'}, {'text': 'dex', 'type': 'Chemical', 'start': 377, 'end': 380, 'mesh': 'D003907'}, {'text': 'bort', 'type': 'Chemical', 'start': 420, 'end': 424, 'mesh': 'C400082'}, {'text': 'MM', 'type': 'Disease', 'start': 471, 'end': 473, 'mesh': 'D009101'}, {'text': 'bort', 'type': 'Chemical', 'start': 717, 'end': 721, 'mesh': 'C400082'}, {'text': 'dex', 'type': 'Chemical', 'start': 722, 'end': 725, 'mesh': 'D003907'}, {'text': 'bort', 'type': 'Chemical', 'start': 748, 'end': 752, 'mesh': 'C400082'}, {'text': 'dex', 'type': 'Chemical', 'start': 753, 'end': 756, 'mesh': 'D003907'}, {'text': 'peripheral neuropathy', 'type': 'Disease', 'start': 1122, 'end': 1143, 'mesh': 'D010523'}, {'text': 'bort', 'type': 'Chemical', 'start': 1505, 'end': 1509, 'mesh': 'C400082'}, {'text': 'dex', 'type': 'Chemical', 'start': 1510, 'end': 1513, 'mesh': 'D003907'}, {'text': 'Bort', 'type': 'Chemical', 'start': 1546, 'end': 1550, 'mesh': 'C400082'}, {'text': 'dex', 'type': 'Chemical', 'start': 1551, 'end': 1554, 'mesh': 'D003907'}, {'text': 'MM', 'type': 'Disease', 'start': 1594, 'end': 1596, 'mesh': 'D009101'}]"
+1008,23871786,Pubertal exposure to Bisphenol A increases anxiety-like behavior and decreases acetylcholinesterase activity of hippocampus in adult male mice.,"The negative effects of Bisphenol A (BPA) on neurodevelopment and behaviors have been well established. Acetylcholinesterase (AChE) is a regulatory enzyme which is involved in anxiety-like behavior. This study investigated behavioral phenotypes and AChE activity in male mice following BPA exposure during puberty. On postnatal day (PND) 35, male mice were exposed to 50mg BPA/kg diet per day for a period of 35 days. On PND71, a behavioral assay was performed using the elevated plus maze (EPM) and the light/dark test. In addition, AChE activity was measured in the prefrontal cortex, hypothalamus, cerebellum and hippocampus. Results from our behavioral phenotyping indicated that anxiety-like behavior was increased in mice exposed to BPA. AChE activity was significantly decreased in the hippocampus of mice with BPA compared to control mice, whereas no difference was found in the prefrontal cortex, hypothalamus and cerebellum. Our findings showed that pubertal BPA exposure increased anxiety-like behavior, which may be associated with decreased AChE activity of the hippocampus in adult male mice. Further studies are necessary to investigate the cholinergic signaling of the hippocampus in PBE induced anxiety-like behaviors.","[{'text': 'Bisphenol A', 'type': 'Chemical', 'start': 21, 'end': 32, 'mesh': 'C006780'}, {'text': 'anxiety', 'type': 'Disease', 'start': 43, 'end': 50, 'mesh': 'D001008'}, {'text': 'Bisphenol A', 'type': 'Chemical', 'start': 168, 'end': 179, 'mesh': 'C006780'}, {'text': 'BPA', 'type': 'Chemical', 'start': 181, 'end': 184, 'mesh': 'C006780'}, {'text': 'anxiety', 'type': 'Disease', 'start': 320, 'end': 327, 'mesh': 'D001008'}, {'text': 'BPA', 'type': 'Chemical', 'start': 430, 'end': 433, 'mesh': 'C006780'}, {'text': 'BPA', 'type': 'Chemical', 'start': 517, 'end': 520, 'mesh': 'C006780'}, {'text': 'anxiety', 'type': 'Disease', 'start': 828, 'end': 835, 'mesh': 'D001008'}, {'text': 'BPA', 'type': 'Chemical', 'start': 883, 'end': 886, 'mesh': 'C006780'}, {'text': 'BPA', 'type': 'Chemical', 'start': 962, 'end': 965, 'mesh': 'C006780'}, {'text': 'BPA', 'type': 'Chemical', 'start': 1113, 'end': 1116, 'mesh': 'C006780'}, {'text': 'anxiety', 'type': 'Disease', 'start': 1136, 'end': 1143, 'mesh': 'D001008'}, {'text': 'anxiety', 'type': 'Disease', 'start': 1356, 'end': 1363, 'mesh': 'D001008'}]"
+1009,23872883,Biochemical effects of Solidago virgaurea extract on experimental cardiotoxicity.,"Cardiovascular diseases (CVDs) are the major health problem of advanced as well as developing countries of the world. The aim of the present study was to investigate the protective effect of the Solidago virgaurea extract on isoproterenol-induced cardiotoxicity in rats. The subcutaneous injection of isoproterenol (30 mg/kg) into rats twice at an interval of 24 h, for two consecutive days, led to a significant increase in serum lactate dehydrogenase, creatine phosphokinase, alanine transaminase, aspartate transaminase, and angiotensin-converting enzyme activities, total cholesterol, triglycerides, free serum fatty acid, cardiac tissue malondialdehyde (MDA), and nitric oxide levels and a significant decrease in levels of glutathione and superoxide dismutase in cardiac tissue as compared to the normal control group (P < 0.05). Pretreatment with S. virgaurea extract for 5 weeks at a dose of 250 mg/kg followed by isoproterenol injection significantly prevented the observed alterations. Captopril (50 mg/kg/day, given orally), an inhibitor of angiotensin-converting enzyme used as a standard cardioprotective drug, was used as a positive control in this study. The data of the present study suggest that S. virgaurea extract exerts its protective effect by decreasing MDA level and increasing the antioxidant status in isoproterenol-treated rats. The study emphasizes the beneficial action of S. virgaurea extract as a cardioprotective agent.","[{'text': 'cardiotoxicity', 'type': 'Disease', 'start': 66, 'end': 80, 'mesh': 'D066126'}, {'text': 'Cardiovascular diseases', 'type': 'Disease', 'start': 82, 'end': 105, 'mesh': 'D002318'}, {'text': 'CVDs', 'type': 'Disease', 'start': 107, 'end': 111, 'mesh': 'D002318'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 307, 'end': 320, 'mesh': 'D007545'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 329, 'end': 343, 'mesh': 'D066126'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 383, 'end': 396, 'mesh': 'D007545'}, {'text': 'lactate', 'type': 'Chemical', 'start': 513, 'end': 520, 'mesh': 'D019344'}, {'text': 'creatine', 'type': 'Chemical', 'start': 536, 'end': 544, 'mesh': 'D003401'}, {'text': 'alanine', 'type': 'Chemical', 'start': 560, 'end': 567, 'mesh': 'D000409'}, {'text': 'aspartate', 'type': 'Chemical', 'start': 582, 'end': 591, 'mesh': 'D001224'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 610, 'end': 621, 'mesh': 'D000809'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 658, 'end': 669, 'mesh': 'D002784'}, {'text': 'triglycerides', 'type': 'Chemical', 'start': 671, 'end': 684, 'mesh': 'D014280'}, {'text': 'fatty acid', 'type': 'Chemical', 'start': 697, 'end': 707, 'mesh': 'D005227'}, {'text': 'malondialdehyde', 'type': 'Chemical', 'start': 724, 'end': 739, 'mesh': 'D008315'}, {'text': 'MDA', 'type': 'Chemical', 'start': 741, 'end': 744, 'mesh': 'D008315'}, {'text': 'nitric oxide', 'type': 'Chemical', 'start': 751, 'end': 763, 'mesh': 'D009569'}, {'text': 'glutathione', 'type': 'Chemical', 'start': 811, 'end': 822, 'mesh': 'D005978'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 827, 'end': 837, 'mesh': 'D013481'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1004, 'end': 1017, 'mesh': 'D007545'}, {'text': 'Captopril', 'type': 'Chemical', 'start': 1078, 'end': 1087, 'mesh': 'D002216'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 1134, 'end': 1145, 'mesh': 'D000809'}, {'text': 'MDA', 'type': 'Chemical', 'start': 1359, 'end': 1362, 'mesh': 'D008315'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1410, 'end': 1423, 'mesh': 'D007545'}]"
+1010,23892921,"""Real-world"" data on the efficacy and safety of lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma who were treated according to the standard clinical practice: a study of the Greek Myeloma Study Group.","Lenalidomide and dexamethasone (RD) is a standard of care for relapsed/refractory multiple myeloma (RRMM), but there is limited published data on its efficacy and safety in the ""real world"" (RW), according to the International Society of Pharmacoeconomics and Outcomes Research definition. We studied 212 RRMM patients who received RD in RW. Objective response (>PR (partial response)) rate was 77.4 % (complete response (CR), 20.2 %). Median time to first and best response was 2 and 5 months, respectively. Median time to CR when RD was given as 2nd or >2(nd)-line treatment at 4 and 11 months, respectively. Quality of response was independent of previous lines of therapies or previous exposure to thalidomide or bortezomib. Median duration of response was 34.4 months, and it was higher in patients who received RD until progression (not reached versus 19 months, p < 0.001). Improvement of humoral immunity occurred in 60 % of responders (p < 0.001) and in the majority of patients who achieved stable disease. Adverse events were reported in 68.9 % of patients (myelosuppression in 49.4 %) and 12.7 % of patients needed hospitalization. Peripheral neuropathy was observed only in 2.5 % of patients and deep vein thrombosis in 5.7 %. Dose reductions were needed in 31 % of patients and permanent discontinuation in 38.9 %. Median time to treatment discontinuation was 16.8 months. Performance status (PS) and initial lenalidomide dose predicted for treatment discontinuation. Extra-medullary relapses occurred in 3.8 % of patients. Our study confirms that RD is effective and safe in RRMM in the RW; it produces durable responses especially in patients who continue on treatment till progression and improves humoral immunity even in patients with stable disease.","[{'text': 'lenalidomide', 'type': 'Chemical', 'start': 48, 'end': 60, 'mesh': 'C467567'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 65, 'end': 78, 'mesh': 'D003907'}, {'text': 'multiple myeloma', 'type': 'Disease', 'start': 116, 'end': 132, 'mesh': 'D009101'}, {'text': 'Myeloma', 'type': 'Disease', 'start': 216, 'end': 223, 'mesh': 'D009101'}, {'text': 'Lenalidomide', 'type': 'Chemical', 'start': 237, 'end': 249, 'mesh': 'C467567'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 254, 'end': 267, 'mesh': 'D003907'}, {'text': 'RD', 'type': 'Chemical', 'start': 269, 'end': 271, 'mesh': 'C467567|D003907'}, {'text': 'multiple myeloma', 'type': 'Disease', 'start': 319, 'end': 335, 'mesh': 'D009101'}, {'text': 'RRMM', 'type': 'Disease', 'start': 337, 'end': 341, 'mesh': 'D009101'}, {'text': 'RRMM', 'type': 'Disease', 'start': 542, 'end': 546, 'mesh': 'D009101'}, {'text': 'RD', 'type': 'Chemical', 'start': 569, 'end': 571, 'mesh': 'C467567|D003907'}, {'text': 'RD', 'type': 'Chemical', 'start': 769, 'end': 771, 'mesh': 'C467567|D003907'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 939, 'end': 950, 'mesh': 'D013792'}, {'text': 'bortezomib', 'type': 'Chemical', 'start': 954, 'end': 964, 'mesh': 'C400082'}, {'text': 'RD', 'type': 'Chemical', 'start': 1054, 'end': 1056, 'mesh': 'C467567|D003907'}, {'text': 'myelosuppression', 'type': 'Disease', 'start': 1306, 'end': 1322, 'mesh': 'D001855'}, {'text': 'Peripheral neuropathy', 'type': 'Disease', 'start': 1381, 'end': 1402, 'mesh': 'D010523'}, {'text': 'deep vein thrombosis', 'type': 'Disease', 'start': 1446, 'end': 1466, 'mesh': 'D020246'}, {'text': 'lenalidomide', 'type': 'Chemical', 'start': 1660, 'end': 1672, 'mesh': 'C467567'}, {'text': 'RD', 'type': 'Chemical', 'start': 1799, 'end': 1801, 'mesh': 'C467567|D003907'}, {'text': 'RRMM', 'type': 'Disease', 'start': 1827, 'end': 1831, 'mesh': 'D009101'}]"
+1011,23949582,"The cytogenetic action of ifosfamide, mesna, and their combination on peripheral rabbit lymphocytes: an in vivo/in vitro cytogenetic study.","Ifosfamide (IFO) is an alkylating nitrogen mustard, administrated as an antineoplasmic agent. It is characterized by its intense urotoxic action, leading to hemorrhagic cystitis. This side effect of IFO raises the requirement for the co-administration with sodium 2-sulfanylethanesulfonate (Mesna) aiming to avoid or minimize this effect. IFO and Mesna were administrated separately on rabbit's lymphocytes in vivo, which were later developed in vitro. Cytogenetic markers for sister chromatid exchanges (SCEs), proliferation rate index (PRI) and Mitotic Index were recorded. Mesna's action, in conjunction with IFO reduces the frequency of SCEs, in comparison with the SCEs recordings obtained when IFO is administered alone. In addition to this, when high concentrations of Mesna were administered alone significant reductions of the PRI were noted, than with IFO acting at the same concentration on the lymphocytes. Mesna significantly reduces IFO's genotoxicity, while when administered in high concentrations it acts in an inhibitory fashion on the cytostatic action of the drug.","[{'text': 'ifosfamide', 'type': 'Chemical', 'start': 26, 'end': 36, 'mesh': 'D007069'}, {'text': 'mesna', 'type': 'Chemical', 'start': 38, 'end': 43, 'mesh': 'D015080'}, {'text': 'Ifosfamide', 'type': 'Chemical', 'start': 140, 'end': 150, 'mesh': 'D007069'}, {'text': 'IFO', 'type': 'Chemical', 'start': 152, 'end': 155, 'mesh': 'D007069'}, {'text': 'nitrogen', 'type': 'Chemical', 'start': 174, 'end': 182, 'mesh': 'D009584'}, {'text': 'IFO', 'type': 'Chemical', 'start': 339, 'end': 342, 'mesh': 'D007069'}, {'text': 'sodium 2-sulfanylethanesulfonate', 'type': 'Chemical', 'start': 397, 'end': 429, 'mesh': 'D015080'}, {'text': 'Mesna', 'type': 'Chemical', 'start': 431, 'end': 436, 'mesh': 'D015080'}, {'text': 'IFO', 'type': 'Chemical', 'start': 479, 'end': 482, 'mesh': 'D007069'}, {'text': 'Mesna', 'type': 'Chemical', 'start': 487, 'end': 492, 'mesh': 'D015080'}, {'text': 'Mesna', 'type': 'Chemical', 'start': 716, 'end': 721, 'mesh': 'D015080'}, {'text': 'IFO', 'type': 'Chemical', 'start': 752, 'end': 755, 'mesh': 'D007069'}, {'text': 'IFO', 'type': 'Chemical', 'start': 840, 'end': 843, 'mesh': 'D007069'}, {'text': 'Mesna', 'type': 'Chemical', 'start': 916, 'end': 921, 'mesh': 'D015080'}, {'text': 'IFO', 'type': 'Chemical', 'start': 1002, 'end': 1005, 'mesh': 'D007069'}, {'text': 'Mesna', 'type': 'Chemical', 'start': 1059, 'end': 1064, 'mesh': 'D015080'}, {'text': 'IFO', 'type': 'Chemical', 'start': 1087, 'end': 1090, 'mesh': 'D007069'}, {'text': 'genotoxicity', 'type': 'Disease', 'start': 1093, 'end': 1105, 'mesh': 'D030342'}]"
+1012,23952588,Risk factors and predictors of levodopa-induced dyskinesia among multiethnic Malaysians with Parkinson's disease.,"Chronic pulsatile levodopa therapy for Parkinson's disease (PD) leads to the development of motor fluctuations and dyskinesia. We studied the prevalence and predictors of levodopa-induced dyskinesia among multiethnic Malaysian patients with PD. METHODS: This is a cross-sectional study involving 95 patients with PD on uninterrupted levodopa therapy for at least 6 months. The instrument used was the UPDRS questionnaires. The predictors of dyskinesia were determined using multivariate logistic regression analysis. RESULTS: The mean age was 65.6 + 8.5 years. The mean onset age was 58.5 + 9.8 years. The median disease duration was 6 (7) years. Dyskinesia was present in 44% (n = 42) with median levodopa therapy of 3 years. There were 64.3% Chinese, 31% Malays, and 3.7% Indians and other ethnic groups. Eighty-one percent of patients with dyskinesia had clinical fluctuations. Patients with dyskinesia had lower onset age ( p < 0.001), longer duration of levodopa therapy ( p < 0.001), longer disease duration ( p < 0.001), higher total daily levodopa dose ( p < 0.001), and higher total UPDRS scores ( p = 0.005) than patients without dyskinesia. The three significant predictors of dyskinesia were duration of levodopa therapy, onset age, and total daily levodopa dose. CONCLUSIONS: The prevalence of levodopa-induced dyskinesia in our patients was 44%. The most significant predictors were duration of levodopa therapy, total daily levodopa dose, and onset age.","[{'text': 'levodopa', 'type': 'Chemical', 'start': 31, 'end': 39, 'mesh': 'D007980'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 48, 'end': 58, 'mesh': 'D004409'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 93, 'end': 112, 'mesh': 'D010300'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 132, 'end': 140, 'mesh': 'D007980'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 153, 'end': 172, 'mesh': 'D010300'}, {'text': 'PD', 'type': 'Disease', 'start': 174, 'end': 176, 'mesh': 'D010300'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 229, 'end': 239, 'mesh': 'D004409'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 285, 'end': 293, 'mesh': 'D007980'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 302, 'end': 312, 'mesh': 'D004409'}, {'text': 'PD', 'type': 'Disease', 'start': 355, 'end': 357, 'mesh': 'D010300'}, {'text': 'PD', 'type': 'Disease', 'start': 427, 'end': 429, 'mesh': 'D010300'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 447, 'end': 455, 'mesh': 'D007980'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 555, 'end': 565, 'mesh': 'D004409'}, {'text': 'Dyskinesia', 'type': 'Disease', 'start': 761, 'end': 771, 'mesh': 'D004409'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 812, 'end': 820, 'mesh': 'D007980'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 957, 'end': 967, 'mesh': 'D004409'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 1009, 'end': 1019, 'mesh': 'D004409'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1073, 'end': 1081, 'mesh': 'D007980'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1161, 'end': 1169, 'mesh': 'D007980'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 1254, 'end': 1264, 'mesh': 'D004409'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 1302, 'end': 1312, 'mesh': 'D004409'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1330, 'end': 1338, 'mesh': 'D007980'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1375, 'end': 1383, 'mesh': 'D007980'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1421, 'end': 1429, 'mesh': 'D007980'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 1438, 'end': 1448, 'mesh': 'D004409'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1523, 'end': 1531, 'mesh': 'D007980'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1553, 'end': 1561, 'mesh': 'D007980'}]"
+1013,24040781,An unexpected diagnosis in a renal-transplant patient with proteinuria treated with everolimus: AL amyloidosis.,"Proteinuria is an expected complication in transplant patients treated with mammalian target of rapamycin inhibitors (mTOR-i). However, clinical suspicion should always be supported by histological evidence in order to investigate potential alternate diagnoses such as acute or chronic rejection, interstitial fibrosis and tubular atrophy, or recurrent or de novo glomerulopathy. In this case we report the unexpected diagnosis of amyloidosis in a renal-transplant patient with pre-transplant monoclonal gammapathy of undetermined significance who developed proteinuria after conversion from tacrolimus to everolimus.","[{'text': 'proteinuria', 'type': 'Disease', 'start': 59, 'end': 70, 'mesh': 'D011507'}, {'text': 'everolimus', 'type': 'Chemical', 'start': 84, 'end': 94, 'mesh': 'C107135'}, {'text': 'AL', 'type': 'Disease', 'start': 96, 'end': 98, 'mesh': 'D000686'}, {'text': 'amyloidosis', 'type': 'Disease', 'start': 99, 'end': 110, 'mesh': 'D000686'}, {'text': 'Proteinuria', 'type': 'Disease', 'start': 112, 'end': 123, 'mesh': 'D011507'}, {'text': 'rapamycin', 'type': 'Chemical', 'start': 208, 'end': 217, 'mesh': 'D020123'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 422, 'end': 430, 'mesh': 'D005355'}, {'text': 'atrophy', 'type': 'Disease', 'start': 443, 'end': 450, 'mesh': 'D001284'}, {'text': 'glomerulopathy', 'type': 'Disease', 'start': 476, 'end': 490, 'mesh': 'D007674'}, {'text': 'amyloidosis', 'type': 'Disease', 'start': 543, 'end': 554, 'mesh': 'D000686'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 670, 'end': 681, 'mesh': 'D011507'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 704, 'end': 714, 'mesh': 'D016559'}, {'text': 'everolimus', 'type': 'Chemical', 'start': 718, 'end': 728, 'mesh': 'C107135'}]"
+1014,24067251,An investigation of the pattern of kidney injury in HIV-positive persons exposed to tenofovir disoproxil fumarate: an examination of a large population database (MHRA database).,"The potential for tenofovir to cause a range of kidney syndromes has been established from mechanistic and randomised clinical trials. However, the exact pattern of kidney involvement is still uncertain. We undertook a descriptive analysis of Yellow Card records of 407 HIV-positive persons taking tenofovir disoproxil fumarate (TDF) as part of their antiretroviral therapy regimen and submitted to the Medicines and Healthcare Products Regulatory Agency (MHRA) with suspected kidney adverse effects. Reports that satisfy defined criteria were classified as acute kidney injury, kidney tubular dysfunction and Fanconi syndrome. Of the 407 Yellow Card records analysed, 106 satisfied criteria for TDF-related kidney disease, of which 53 (50%) had features of kidney tubular dysfunction, 35 (33%) were found to have features of glomerular dysfunction and 18 (17%) had Fanconi syndrome. The median TDF exposure was 316 days (interquartile range 120-740). The incidence of hospitalisation for TDF kidney adverse effects was high, particularly amongst patients with features of Fanconi syndrome. The pattern of kidney syndromes in this population series mirrors that reported in randomised clinical trials. Cessation of TDF was associated with complete restoration of kidney function in up half of the patients in this report.","[{'text': 'kidney injury', 'type': 'Disease', 'start': 35, 'end': 48, 'mesh': 'D007674'}, {'text': 'tenofovir disoproxil fumarate', 'type': 'Chemical', 'start': 84, 'end': 113, 'mesh': 'C418563'}, {'text': 'tenofovir', 'type': 'Chemical', 'start': 196, 'end': 205, 'mesh': 'C096918'}, {'text': 'tenofovir disoproxil fumarate', 'type': 'Chemical', 'start': 476, 'end': 505, 'mesh': 'C418563'}, {'text': 'TDF', 'type': 'Chemical', 'start': 507, 'end': 510, 'mesh': 'C418563'}, {'text': 'acute kidney injury', 'type': 'Disease', 'start': 736, 'end': 755, 'mesh': 'D058186'}, {'text': 'kidney tubular dysfunction', 'type': 'Disease', 'start': 757, 'end': 783, 'mesh': 'D007674'}, {'text': 'Fanconi syndrome', 'type': 'Disease', 'start': 788, 'end': 804, 'mesh': 'D005198'}, {'text': 'TDF', 'type': 'Chemical', 'start': 874, 'end': 877, 'mesh': 'C418563'}, {'text': 'kidney disease', 'type': 'Disease', 'start': 886, 'end': 900, 'mesh': 'D007674'}, {'text': 'kidney tubular dysfunction', 'type': 'Disease', 'start': 936, 'end': 962, 'mesh': 'D007674'}, {'text': 'glomerular dysfunction', 'type': 'Disease', 'start': 1004, 'end': 1026, 'mesh': 'D007674'}, {'text': 'Fanconi syndrome', 'type': 'Disease', 'start': 1044, 'end': 1060, 'mesh': 'D005198'}, {'text': 'TDF', 'type': 'Chemical', 'start': 1073, 'end': 1076, 'mesh': 'C418563'}, {'text': 'TDF', 'type': 'Chemical', 'start': 1167, 'end': 1170, 'mesh': 'C418563'}, {'text': 'Fanconi syndrome', 'type': 'Disease', 'start': 1251, 'end': 1267, 'mesh': 'D005198'}, {'text': 'TDF', 'type': 'Chemical', 'start': 1393, 'end': 1396, 'mesh': 'C418563'}]"
+1015,24068571,Incidence of postoperative delirium is high even in a population without known risk factors.,"PURPOSE: Postoperative delirium is a recognized complication in populations at risk. The aim of this study is to assess the prevalence of early postoperative delirium in a population without known risk factors admitted to the ICU for postoperative monitoring after elective major surgery. The secondary outcome investigated is to identify eventual independent risk factors among demographic data and anesthetic drugs used. METHODS: An observational, prospective study was conducted on a consecutive cohort of patients admitted to our ICU within and for at least 24 h after major surgical procedures. Exclusion criteria were any preexisting predisposing factor for delirium or other potentially confounding neurological dysfunctions. Patients were assessed daily using the confusion assessment method for the ICU scale for 3 days after the surgical procedure. Early postoperative delirium incidence risk factors were then assessed through three different multiple regression models. RESULTS: According to the confusion assessment method for the ICU scale, 28 % of patients were diagnosed with early postoperative delirium. The use of thiopentone was significantly associated with an eight-fold-higher risk for delirium compared to propofol (57.1% vs. 7.1%, RR = 8.0, X2 = 4.256; df = 1; 0.05 < p < 0.02). CONCLUSION: In this study early postoperative delirium was found to be a very common complication after major surgery, even in a population without known risk factors. Thiopentone was independently associated with an increase in its relative risk.","[{'text': 'postoperative delirium', 'type': 'Disease', 'start': 13, 'end': 35, 'mesh': 'D011183'}, {'text': 'Postoperative delirium', 'type': 'Disease', 'start': 102, 'end': 124, 'mesh': 'D011183'}, {'text': 'postoperative delirium', 'type': 'Disease', 'start': 237, 'end': 259, 'mesh': 'D011183'}, {'text': 'delirium', 'type': 'Disease', 'start': 757, 'end': 765, 'mesh': 'D003693'}, {'text': 'neurological dysfunctions', 'type': 'Disease', 'start': 799, 'end': 824, 'mesh': 'D009422'}, {'text': 'confusion', 'type': 'Disease', 'start': 865, 'end': 874, 'mesh': 'D003221'}, {'text': 'postoperative delirium', 'type': 'Disease', 'start': 958, 'end': 980, 'mesh': 'D011183'}, {'text': 'postoperative delirium', 'type': 'Disease', 'start': 1191, 'end': 1213, 'mesh': 'D011183'}, {'text': 'thiopentone', 'type': 'Chemical', 'start': 1226, 'end': 1237, 'mesh': 'D013874'}, {'text': 'delirium', 'type': 'Disease', 'start': 1302, 'end': 1310, 'mesh': 'D003693'}, {'text': 'propofol', 'type': 'Chemical', 'start': 1323, 'end': 1331, 'mesh': 'D015742'}, {'text': 'postoperative delirium', 'type': 'Disease', 'start': 1429, 'end': 1451, 'mesh': 'D011183'}, {'text': 'Thiopentone', 'type': 'Chemical', 'start': 1565, 'end': 1576, 'mesh': 'D013874'}]"
+1016,24072398,A single neurotoxic dose of methamphetamine induces a long-lasting depressive-like behaviour in mice.,"Methamphetamine (METH) triggers a disruption of the monoaminergic system and METH abuse leads to negative emotional states including depressive symptoms during drug withdrawal. However, it is currently unknown if the acute toxic dosage of METH also causes a long-lasting depressive phenotype and persistent monoaminergic deficits. Thus, we now assessed the depressive-like behaviour in mice at early and long-term periods following a single high METH dose (30 mg/kg, i.p.). METH did not alter the motor function and procedural memory of mice as assessed by swimming speed and escape latency to find the platform in a cued version of the water maze task. However, METH significantly increased the immobility time in the tail suspension test at 3 and 49 days post-administration. This depressive-like profile induced by METH was accompanied by a marked depletion of frontostriatal dopaminergic and serotonergic neurotransmission, indicated by a reduction in the levels of dopamine, DOPAC and HVA, tyrosine hydroxylase and serotonin, observed at both 3 and 49 days post-administration. In parallel, another neurochemical feature of depression--astroglial dysfunction--was unaffected in the cortex and the striatal levels of the astrocytic protein marker, glial fibrillary acidic protein, were only transiently increased at 3 days. These findings demonstrate for the first time that a single high dose of METH induces long-lasting depressive-like behaviour in mice associated with a persistent disruption of frontostriatal dopaminergic and serotonergic homoeostasis.","[{'text': 'neurotoxic', 'type': 'Disease', 'start': 9, 'end': 19, 'mesh': 'D020258'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 28, 'end': 43, 'mesh': 'D008694'}, {'text': 'depressive', 'type': 'Disease', 'start': 67, 'end': 77, 'mesh': 'D003866'}, {'text': 'Methamphetamine', 'type': 'Chemical', 'start': 102, 'end': 117, 'mesh': 'D008694'}, {'text': 'METH', 'type': 'Chemical', 'start': 119, 'end': 123, 'mesh': 'D008694'}, {'text': 'METH', 'type': 'Chemical', 'start': 179, 'end': 183, 'mesh': 'D008694'}, {'text': 'depressive symptoms', 'type': 'Disease', 'start': 235, 'end': 254, 'mesh': 'D003866'}, {'text': 'METH', 'type': 'Chemical', 'start': 341, 'end': 345, 'mesh': 'D008694'}, {'text': 'depressive', 'type': 'Disease', 'start': 373, 'end': 383, 'mesh': 'D003866'}, {'text': 'depressive', 'type': 'Disease', 'start': 459, 'end': 469, 'mesh': 'D003866'}, {'text': 'METH', 'type': 'Chemical', 'start': 548, 'end': 552, 'mesh': 'D008694'}, {'text': 'METH', 'type': 'Chemical', 'start': 576, 'end': 580, 'mesh': 'D008694'}, {'text': 'METH', 'type': 'Chemical', 'start': 765, 'end': 769, 'mesh': 'D008694'}, {'text': 'depressive', 'type': 'Disease', 'start': 885, 'end': 895, 'mesh': 'D003866'}, {'text': 'METH', 'type': 'Chemical', 'start': 920, 'end': 924, 'mesh': 'D008694'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1072, 'end': 1080, 'mesh': 'D004298'}, {'text': 'DOPAC', 'type': 'Chemical', 'start': 1082, 'end': 1087, 'mesh': 'D015102'}, {'text': 'HVA', 'type': 'Chemical', 'start': 1092, 'end': 1095, 'mesh': 'D006719'}, {'text': 'tyrosine', 'type': 'Chemical', 'start': 1097, 'end': 1105, 'mesh': 'D014443'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 1122, 'end': 1131, 'mesh': 'D012701'}, {'text': 'depression', 'type': 'Disease', 'start': 1231, 'end': 1241, 'mesh': 'D003866'}, {'text': 'METH', 'type': 'Chemical', 'start': 1503, 'end': 1507, 'mesh': 'D008694'}, {'text': 'depressive', 'type': 'Disease', 'start': 1529, 'end': 1539, 'mesh': 'D003866'}]"
+1017,24088636,Linezolid-induced optic neuropathy.,Many systemic antimicrobials have been implicated to cause ocular adverse effects. This is especially relevant in multidrug therapy where more than one drug can cause a similar ocular adverse effect. We describe a case of progressive loss of vision associated with linezolid therapy. A 45-year-old male patient who was on treatment with multiple second-line anti-tuberculous drugs including linezolid and ethambutol for extensively drug-resistant tuberculosis (XDR-TB) presented to us with painless progressive loss of vision in both eyes. Color vision was defective and fundus examination revealed optic disc edema in both eyes. Ethambutol-induced toxic optic neuropathy was suspected and tablet ethambutol was withdrawn. Deterioration of vision occurred despite withdrawal of ethambutol. Discontinuation of linezolid resulted in marked improvement of vision. Our report emphasizes the need for monitoring of visual function in patients on long-term linezolid treatment.,"[{'text': 'Linezolid', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'C098010'}, {'text': 'optic neuropathy', 'type': 'Disease', 'start': 18, 'end': 34, 'mesh': 'D009901'}, {'text': 'loss of vision', 'type': 'Disease', 'start': 270, 'end': 284, 'mesh': 'D014786'}, {'text': 'linezolid', 'type': 'Chemical', 'start': 301, 'end': 310, 'mesh': 'C098010'}, {'text': 'linezolid', 'type': 'Chemical', 'start': 427, 'end': 436, 'mesh': 'C098010'}, {'text': 'ethambutol', 'type': 'Chemical', 'start': 441, 'end': 451, 'mesh': 'D004977'}, {'text': 'extensively drug-resistant tuberculosis', 'type': 'Disease', 'start': 456, 'end': 495, 'mesh': 'D054908'}, {'text': 'XDR-TB', 'type': 'Disease', 'start': 497, 'end': 503, 'mesh': 'D054908'}, {'text': 'loss of vision', 'type': 'Disease', 'start': 547, 'end': 561, 'mesh': 'D014786'}, {'text': 'optic disc edema', 'type': 'Disease', 'start': 635, 'end': 651, 'mesh': 'C531767'}, {'text': 'Ethambutol', 'type': 'Chemical', 'start': 666, 'end': 676, 'mesh': 'D004977'}, {'text': 'toxic optic neuropathy', 'type': 'Disease', 'start': 685, 'end': 707, 'mesh': 'D009901'}, {'text': 'ethambutol', 'type': 'Chemical', 'start': 733, 'end': 743, 'mesh': 'D004977'}, {'text': 'Deterioration of vision', 'type': 'Disease', 'start': 759, 'end': 782, 'mesh': 'D015354'}, {'text': 'ethambutol', 'type': 'Chemical', 'start': 814, 'end': 824, 'mesh': 'D004977'}, {'text': 'linezolid', 'type': 'Chemical', 'start': 845, 'end': 854, 'mesh': 'C098010'}, {'text': 'linezolid', 'type': 'Chemical', 'start': 987, 'end': 996, 'mesh': 'C098010'}]"
+1018,24091473,"Resuscitation with lipid, epinephrine, or both in levobupivacaine-induced cardiac toxicity in newborn piglets.","BACKGROUND: The optimal dosing regimens of lipid emulsion, epinephrine, or both are not yet determined in neonates in cases of local anaesthetic systemic toxicity (LAST). METHODS: Newborn piglets received levobupivacaine until cardiovascular collapse occurred. Standard cardiopulmonary resuscitation was started and electrocardiogram (ECG) was monitored for ventricular tachycardia, fibrillation, or QRS prolongation. Piglets were then randomly allocated to four groups: control (saline), Intralipid( ) alone, epinephrine alone, or a combination of Intralipd plus epinephrine. Resuscitation continued for 30 min or until there was a return of spontaneous circulation (ROSC) accompanied by a mean arterial pressure at or superior to the baseline pressure and normal sinus rhythm for a period of 30 min. RESULTS: ROSC was achieved in only one of the control piglets compared with most of the treated piglets. Mortality was not significantly different between the three treatment groups, but was significantly lower in all the treatment groups compared with control. The number of ECG abnormalities was zero in the Intralipid only group, but 14 and 17, respectively, in the epinephrine and epinephrine plus lipid groups (P<0.05). CONCLUSIONS: Lipid emulsion with or without epinephrine, or epinephrine alone were equally effective in achieving a return to spontaneous circulation in this model of LAST. Epinephrine alone or in combination with lipid was associated with an increased number of ECG abnormalities compared with lipid emulsion alone.","[{'text': 'epinephrine', 'type': 'Chemical', 'start': 26, 'end': 37, 'mesh': 'D004837'}, {'text': 'levobupivacaine', 'type': 'Chemical', 'start': 50, 'end': 65, 'mesh': 'C476513'}, {'text': 'cardiac toxicity', 'type': 'Disease', 'start': 74, 'end': 90, 'mesh': 'D066126'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 170, 'end': 181, 'mesh': 'D004837'}, {'text': 'toxicity', 'type': 'Disease', 'start': 265, 'end': 273, 'mesh': 'D064420'}, {'text': 'levobupivacaine', 'type': 'Chemical', 'start': 316, 'end': 331, 'mesh': 'C476513'}, {'text': 'cardiovascular collapse', 'type': 'Disease', 'start': 338, 'end': 361, 'mesh': 'D002318'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 469, 'end': 492, 'mesh': 'D017180'}, {'text': 'fibrillation', 'type': 'Disease', 'start': 494, 'end': 506, 'mesh': 'D001281'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 621, 'end': 632, 'mesh': 'D004837'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 675, 'end': 686, 'mesh': 'D004837'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 1282, 'end': 1293, 'mesh': 'D004837'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 1298, 'end': 1309, 'mesh': 'D004837'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 1382, 'end': 1393, 'mesh': 'D004837'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 1398, 'end': 1409, 'mesh': 'D004837'}, {'text': 'Epinephrine', 'type': 'Chemical', 'start': 1511, 'end': 1522, 'mesh': 'D004837'}]"
+1019,24100055,Incidence of heparin-induced thrombocytopenia type II and postoperative recovery of platelet count in liver graft recipients: a retrospective cohort analysis.,"BACKGROUND: Thrombocytopenia in patients with end-stage liver disease is a common disorder caused mainly by portal hypertension, low levels of thrombopoetin, and endotoxemia. The impact of immune-mediated heparin-induced thrombocytopenia type II (HIT type II) as a cause of thrombocytopenia after liver transplantation is not yet understood, with few literature citations reporting contradictory results. The aim of our study was to demonstrate the perioperative course of thrombocytopenia after liver transplantation and determine the occurrence of clinical HIT type II. METHOD: We retrospectively evaluated the medical records of 205 consecutive adult patients who underwent full-size liver transplantation between January 2006 and December 2010 due to end-stage or malignant liver disease. Preoperative platelet count, postoperative course of platelets, and clinical signs of HIT type II were analyzed. RESULTS: A total of 155 (75.6%) of 205 patients had thrombocytopenia before transplantation, significantly influenced by Model of End-Stage Liver Disease score and liver cirrhosis. The platelet count exceeded 100,000/uL in most of the patients (n = 193) at a medium of 7 d. Regarding HIT II, there were four (1.95%) patients with a background of HIT type II. CONCLUSIONS: The incidence of HIT in patients with end-stage hepatic failure is, with about 1.95%, rare. For further reduction of HIT type II, the use of intravenous heparin should be avoided and the prophylactic anticoagulation should be performed with low-molecular-weight heparin after normalization of platelet count.","[{'text': 'heparin', 'type': 'Chemical', 'start': 13, 'end': 20, 'mesh': 'D006493'}, {'text': 'thrombocytopenia type II', 'type': 'Disease', 'start': 29, 'end': 53, 'mesh': 'D013921'}, {'text': 'Thrombocytopenia', 'type': 'Disease', 'start': 171, 'end': 187, 'mesh': 'D013921'}, {'text': 'end-stage liver disease', 'type': 'Disease', 'start': 205, 'end': 228, 'mesh': 'D058625'}, {'text': 'portal hypertension', 'type': 'Disease', 'start': 267, 'end': 286, 'mesh': 'D006975'}, {'text': 'endotoxemia', 'type': 'Disease', 'start': 321, 'end': 332, 'mesh': 'D019446'}, {'text': 'heparin', 'type': 'Chemical', 'start': 364, 'end': 371, 'mesh': 'D006493'}, {'text': 'thrombocytopenia type II', 'type': 'Disease', 'start': 380, 'end': 404, 'mesh': 'D013921'}, {'text': 'HIT type II', 'type': 'Disease', 'start': 406, 'end': 417, 'mesh': 'D013921'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 433, 'end': 449, 'mesh': 'D013921'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 632, 'end': 648, 'mesh': 'D013921'}, {'text': 'HIT type II', 'type': 'Disease', 'start': 718, 'end': 729, 'mesh': 'D013921'}, {'text': 'HIT type II', 'type': 'Disease', 'start': 1038, 'end': 1049, 'mesh': 'D013921'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 1117, 'end': 1133, 'mesh': 'D013921'}, {'text': 'End-Stage Liver Disease', 'type': 'Disease', 'start': 1195, 'end': 1218, 'mesh': 'D058625'}, {'text': 'liver cirrhosis', 'type': 'Disease', 'start': 1229, 'end': 1244, 'mesh': 'D008103'}, {'text': 'HIT II', 'type': 'Disease', 'start': 1349, 'end': 1355, 'mesh': 'D013921'}, {'text': 'HIT type II', 'type': 'Disease', 'start': 1411, 'end': 1422, 'mesh': 'D013921'}, {'text': 'HIT', 'type': 'Disease', 'start': 1454, 'end': 1457, 'mesh': 'D013921'}, {'text': 'end-stage hepatic failure', 'type': 'Disease', 'start': 1475, 'end': 1500, 'mesh': 'D058625'}, {'text': 'HIT type II', 'type': 'Disease', 'start': 1554, 'end': 1565, 'mesh': 'D013921'}, {'text': 'heparin', 'type': 'Chemical', 'start': 1590, 'end': 1597, 'mesh': 'D006493'}, {'text': 'heparin', 'type': 'Chemical', 'start': 1699, 'end': 1706, 'mesh': 'D006493'}]"
+1020,24100257,Takotsubo syndrome (or apical ballooning syndrome) secondary to Zolmitriptan.,"Takotsubo syndrome (TS), also known as broken heart syndrome, is characterized by left ventricle apical ballooning with elevated cardiac biomarkers and electrocardiographic changes suggestive of an acute coronary syndrome (ie, ST-segment elevation, T wave inversions, and pathologic Q waves). We report a case of 54-year-old woman with medical history of mitral valve prolapse and migraines, who was admitted to the hospital for substernal chest pain and electrocardiogram demonstrated 1/2 mm ST-segment elevation in leads II, III, aVF, V5, and V6 and positive troponin I. Emergent coronary angiogram revealed normal coronary arteries with moderately reduced left ventricular ejection fraction with wall motion abnormalities consistent with TS. Detailed history obtained retrospectively revealed that the patient took zolmitriptan sparingly only when she had migraines. But before this event, she was taking zolmitriptan 2-3 times daily for several days because of a persistent migraine headache. She otherwise reported that she is quite active, rides horses, and does show jumping without any limitations in her physical activity. There was no evidence of any recent stress or status migrainosus. Extensive literature search revealed multiple cases of coronary artery vasospasm secondary to zolmitriptan, but none of the cases were associated with TS.","[{'text': 'Takotsubo syndrome', 'type': 'Disease', 'start': 0, 'end': 18, 'mesh': 'D054549'}, {'text': 'apical ballooning syndrome', 'type': 'Disease', 'start': 23, 'end': 49, 'mesh': 'D054549'}, {'text': 'Zolmitriptan', 'type': 'Chemical', 'start': 64, 'end': 76, 'mesh': 'C089750'}, {'text': 'Takotsubo syndrome', 'type': 'Disease', 'start': 78, 'end': 96, 'mesh': 'D054549'}, {'text': 'TS', 'type': 'Disease', 'start': 98, 'end': 100, 'mesh': 'D054549'}, {'text': 'broken heart syndrome', 'type': 'Disease', 'start': 117, 'end': 138, 'mesh': 'D054549'}, {'text': 'acute coronary syndrome', 'type': 'Disease', 'start': 276, 'end': 299, 'mesh': 'D054058'}, {'text': 'mitral valve prolapse', 'type': 'Disease', 'start': 433, 'end': 454, 'mesh': 'D008945'}, {'text': 'migraines', 'type': 'Disease', 'start': 459, 'end': 468, 'mesh': 'D008881'}, {'text': 'chest pain', 'type': 'Disease', 'start': 518, 'end': 528, 'mesh': 'D002637'}, {'text': 'TS', 'type': 'Disease', 'start': 819, 'end': 821, 'mesh': 'D054549'}, {'text': 'zolmitriptan', 'type': 'Chemical', 'start': 896, 'end': 908, 'mesh': 'C089750'}, {'text': 'migraines', 'type': 'Disease', 'start': 937, 'end': 946, 'mesh': 'D008881'}, {'text': 'zolmitriptan', 'type': 'Chemical', 'start': 986, 'end': 998, 'mesh': 'C089750'}, {'text': 'migraine headache', 'type': 'Disease', 'start': 1056, 'end': 1073, 'mesh': 'D008881'}, {'text': 'status migrainosus', 'type': 'Disease', 'start': 1256, 'end': 1274, 'mesh': 'D008881'}, {'text': 'coronary artery vasospasm', 'type': 'Disease', 'start': 1331, 'end': 1356, 'mesh': 'D003329'}, {'text': 'zolmitriptan', 'type': 'Chemical', 'start': 1370, 'end': 1382, 'mesh': 'C089750'}, {'text': 'TS', 'type': 'Disease', 'start': 1427, 'end': 1429, 'mesh': 'D054549'}]"
+1021,24114426,"Depression, impulsiveness, sleep, and memory in past and present polydrug users of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy).","RATIONALE: Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a worldwide recreational drug of abuse. Unfortunately, the results from human research investigating its psychological effects have been inconsistent. OBJECTIVES: The present study aimed to be the largest to date in sample size and 5HT-related behaviors; the first to compare present ecstasy users with past users after an abstinence of 4 or more years, and the first to include robust controls for other recreational substances. METHODS: A sample of 997 participants (52 % male) was recruited to four control groups (non-drug (ND), alcohol/nicotine (AN), cannabis/alcohol/nicotine (CAN), non-ecstasy polydrug (PD)), and two ecstasy polydrug groups (present (MDMA) and past users (EX-MDMA). Participants completed a drug history questionnaire, Beck Depression Inventory, Barratt Impulsiveness Scale, Pittsburgh Sleep Quality Index, and Wechsler Memory Scale-Revised which, in total, provided 13 psychometric measures. RESULTS: While the CAN and PD groups tended to record greater deficits than the non-drug controls, the MDMA and EX-MDMA groups recorded greater deficits than all the control groups on ten of the 13 psychometric measures. Strikingly, despite prolonged abstinence (mean, 4.98; range, 4-9 years), past ecstasy users showed few signs of recovery. Compared with present ecstasy users, the past users showed no change for ten measures, increased impairment for two measures, and improvement on just one measure. CONCLUSIONS: Given this record of impaired memory and clinically significant levels of depression, impulsiveness, and sleep disturbance, the prognosis for the current generation of ecstasy users is a major cause for concern.","[{'text': 'Depression', 'type': 'Disease', 'start': 0, 'end': 10, 'mesh': 'D003866'}, {'text': 'impulsiveness', 'type': 'Disease', 'start': 12, 'end': 25, 'mesh': 'D010554'}, {'text': '3,4-methylenedioxymethamphetamine', 'type': 'Chemical', 'start': 83, 'end': 116, 'mesh': 'D018817'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 118, 'end': 122, 'mesh': 'D018817'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 124, 'end': 131, 'mesh': 'D018817'}, {'text': 'Ecstasy', 'type': 'Chemical', 'start': 145, 'end': 152, 'mesh': 'D018817'}, {'text': '3,4-methylenedioxymethamphetamine', 'type': 'Chemical', 'start': 154, 'end': 187, 'mesh': 'D018817'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 189, 'end': 193, 'mesh': 'D018817'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 482, 'end': 489, 'mesh': 'D018817'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 731, 'end': 738, 'mesh': 'D000431'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 739, 'end': 747, 'mesh': 'D009538'}, {'text': 'AN', 'type': 'Chemical', 'start': 749, 'end': 751, 'mesh': 'D000431|D009538'}, {'text': 'cannabis', 'type': 'Chemical', 'start': 754, 'end': 762, 'mesh': 'D002188'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 763, 'end': 770, 'mesh': 'D000431'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 771, 'end': 779, 'mesh': 'D009538'}, {'text': 'CAN', 'type': 'Chemical', 'start': 781, 'end': 784, 'mesh': 'D002188|D000431|D009538'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 791, 'end': 798, 'mesh': 'D018817'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 823, 'end': 830, 'mesh': 'D018817'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 857, 'end': 861, 'mesh': 'D018817'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 882, 'end': 886, 'mesh': 'D018817'}, {'text': 'Depression', 'type': 'Disease', 'start': 947, 'end': 957, 'mesh': 'D003866'}, {'text': 'Impulsiveness', 'type': 'Disease', 'start': 977, 'end': 990, 'mesh': 'D010554'}, {'text': 'CAN', 'type': 'Chemical', 'start': 1135, 'end': 1138, 'mesh': 'D002188|D000431|D009538'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 1219, 'end': 1223, 'mesh': 'D018817'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 1231, 'end': 1235, 'mesh': 'D018817'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 1415, 'end': 1422, 'mesh': 'D018817'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 1481, 'end': 1488, 'mesh': 'D018817'}, {'text': 'impaired memory', 'type': 'Disease', 'start': 1656, 'end': 1671, 'mesh': 'D008569'}, {'text': 'depression', 'type': 'Disease', 'start': 1709, 'end': 1719, 'mesh': 'D003866'}, {'text': 'impulsiveness', 'type': 'Disease', 'start': 1721, 'end': 1734, 'mesh': 'D010554'}, {'text': 'sleep disturbance', 'type': 'Disease', 'start': 1740, 'end': 1757, 'mesh': 'D020920'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 1803, 'end': 1810, 'mesh': 'D018817'}]"
+1022,24126708,Association of common genetic variants of HOMER1 gene with levodopa adverse effects in Parkinson's disease patients.,"Levodopa is the most effective symptomatic therapy for Parkinson's disease, but its chronic use could lead to chronic adverse outcomes, such as motor fluctuations, dyskinesia and visual hallucinations. HOMER1 is a protein with pivotal function in glutamate transmission, which has been related to the pathogenesis of these complications. This study investigates whether polymorphisms in the HOMER1 gene promoter region are associated with the occurrence of the chronic complications of levodopa therapy. A total of 205 patients with idiopathic Parkinson's disease were investigated. Patients were genotyped for rs4704559, rs10942891 and rs4704560 by allelic discrimination with Taqman assays. The rs4704559 G allele was associated with a lower prevalence of dyskinesia (prevalence ratio (PR)=0.615, 95% confidence interval (CI) 0.426-0.887, P=0.009) and visual hallucinations (PR=0.515, 95% CI 0.295-0.899, P=0.020). Our data suggest that HOMER1 rs4704559 G allele has a protective role for the development of levodopa adverse effects.","[{'text': 'levodopa', 'type': 'Chemical', 'start': 59, 'end': 67, 'mesh': 'D007980'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 87, 'end': 106, 'mesh': 'D010300'}, {'text': 'Levodopa', 'type': 'Chemical', 'start': 117, 'end': 125, 'mesh': 'D007980'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 172, 'end': 191, 'mesh': 'D010300'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 281, 'end': 291, 'mesh': 'D004409'}, {'text': 'visual hallucinations', 'type': 'Disease', 'start': 296, 'end': 317, 'mesh': 'D006212'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 364, 'end': 373, 'mesh': 'D018698'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 603, 'end': 611, 'mesh': 'D007980'}, {'text': ""idiopathic Parkinson's disease"", 'type': 'Disease', 'start': 650, 'end': 680, 'mesh': 'D010300'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 875, 'end': 885, 'mesh': 'D004409'}, {'text': 'visual hallucinations', 'type': 'Disease', 'start': 971, 'end': 992, 'mesh': 'D006212'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1127, 'end': 1135, 'mesh': 'D007980'}]"
+1023,24132704,Crocin improves lipid dysregulation in subacute diazinon exposure through ERK1/2 pathway in rat liver.,"INTRODUCTION: Diazinon Yis one of the most broadly used organophosphorus insecticides in agriculture. It has been shown that exposure to diazinon may interfere with lipid metabolism. Moreover, the hypolipidemic effect of crocin has been established. Earlier studies revealed the major role of Extracellular signal-regulated kinase (ERK) pathways in low-density lipoprotein receptor (LDLr) expression. The aim of this study was to evaluate changes in the regulation of lipid metabolism, ERK and LDLr expression in the liver of rats exposed to subacute diazinon. Furthermore ameliorating effect of crocin on diazinon induced disturbed cholesterol homeostasis was studied. METHODS: 24 Rats were divided into 4 groups and received following treatments for 4 weeks; Corn oil (control), diazinon (15mg/kg per day, orally) and crocin (12.5 and 25mg/kg per day, intraperitoneally) in combination with diazinon (15 mg/kg). The levels of cholesterol, triglyceride and LDL in blood of rats were analyzed. Moreover mRNA levels of LDLr and ERK1/2 as well as protein levels of total and activated forms of ERK1/2 in rat liver were evaluated by Western blotting and quantitative real time polymerase chain reaction analysis. RESULTS: Our data showed that subacute exposure to diazinon significantly increased concentrations of cholesterol, triglyceride and LDL. Moreover diazinon decreased ERK1/2 protein phosphorylation and LDLr transcript. Crocin reduced inhibition of ERK activation and diazinon-induced hyperlipemia and increased levels of LDLr transcript. CONCLUSIONS: Crocin may be considered as a novel protective agent in diazinon-induced hyperlipemia through modulating of ERK pathway and increase of LDLr expression.","[{'text': 'Crocin', 'type': 'Chemical', 'start': 0, 'end': 6, 'mesh': 'C029036'}, {'text': 'diazinon', 'type': 'Chemical', 'start': 48, 'end': 56, 'mesh': 'D003976'}, {'text': 'Diazinon', 'type': 'Chemical', 'start': 117, 'end': 125, 'mesh': 'D003976'}, {'text': 'organophosphorus', 'type': 'Chemical', 'start': 159, 'end': 175, 'mesh': 'D010755'}, {'text': 'diazinon', 'type': 'Chemical', 'start': 240, 'end': 248, 'mesh': 'D003976'}, {'text': 'crocin', 'type': 'Chemical', 'start': 324, 'end': 330, 'mesh': 'C029036'}, {'text': 'diazinon', 'type': 'Chemical', 'start': 654, 'end': 662, 'mesh': 'D003976'}, {'text': 'crocin', 'type': 'Chemical', 'start': 699, 'end': 705, 'mesh': 'C029036'}, {'text': 'diazinon', 'type': 'Chemical', 'start': 709, 'end': 717, 'mesh': 'D003976'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 736, 'end': 747, 'mesh': 'D002784'}, {'text': 'diazinon', 'type': 'Chemical', 'start': 884, 'end': 892, 'mesh': 'D003976'}, {'text': 'crocin', 'type': 'Chemical', 'start': 923, 'end': 929, 'mesh': 'C029036'}, {'text': 'diazinon', 'type': 'Chemical', 'start': 996, 'end': 1004, 'mesh': 'D003976'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 1031, 'end': 1042, 'mesh': 'D002784'}, {'text': 'triglyceride', 'type': 'Chemical', 'start': 1044, 'end': 1056, 'mesh': 'D014280'}, {'text': 'diazinon', 'type': 'Chemical', 'start': 1364, 'end': 1372, 'mesh': 'D003976'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 1415, 'end': 1426, 'mesh': 'D002784'}, {'text': 'triglyceride', 'type': 'Chemical', 'start': 1428, 'end': 1440, 'mesh': 'D014280'}, {'text': 'diazinon', 'type': 'Chemical', 'start': 1459, 'end': 1467, 'mesh': 'D003976'}, {'text': 'Crocin', 'type': 'Chemical', 'start': 1530, 'end': 1536, 'mesh': 'C029036'}, {'text': 'diazinon', 'type': 'Chemical', 'start': 1578, 'end': 1586, 'mesh': 'D003976'}, {'text': 'hyperlipemia', 'type': 'Disease', 'start': 1595, 'end': 1607, 'mesh': 'D006949'}, {'text': 'Crocin', 'type': 'Chemical', 'start': 1662, 'end': 1668, 'mesh': 'C029036'}, {'text': 'diazinon', 'type': 'Chemical', 'start': 1718, 'end': 1726, 'mesh': 'D003976'}, {'text': 'hyperlipemia', 'type': 'Disease', 'start': 1735, 'end': 1747, 'mesh': 'D006949'}]"
+1024,24158386,GEM-P chemotherapy is active in the treatment of relapsed Hodgkin lymphoma.,"Hodgkin lymphoma (HL) is a relatively chemosensitive malignancy. However, for those who relapse, high-dose chemotherapy with autologous stem cell transplant is the treatment of choice which relies on adequate disease control with salvage chemotherapy. Regimens commonly used often require inpatient administration and can be difficult to deliver due to toxicity. Gemcitabine and cisplatin have activity in HL, non-overlapping toxicity with first-line chemotherapeutics, and may be delivered in an outpatient setting. In this retrospective single-centre analysis, patients with relapsed or refractory HL treated with gemcitabine 1,000 mg/m(2) day (D)1, D8 and D15; methylprednisolone 1,000 mg D1-5; and cisplatin 100 mg/m(2) D15, every 28 days (GEM-P) were included. Demographic, survival, response and toxicity data were recorded. Forty-one eligible patients were identified: median age 27. One hundred and twenty-two cycles of GEM-P were administered in total (median 3 cycles; range 1-6). Twenty of 41 (48 %) patients received GEM-P as second-line treatment and 11/41 (27 %) as third-line therapy. Overall response rate (ORR) to GEM-P in the entire cohort was 80 % (complete response (CR) 37 %, partial response 44 %) with 14/15 CR confirmed as a metabolic CR on PET and ORR of 85 % in the 20 second-line patients. The most common grade 3/4 toxicities were haematological: neutropenia 54 % and thrombocytopenia 51 %. Median follow-up from the start of GEM-P was 4.5 years. Following GEM-P, 5-year progression-free survival was 46 % (95 % confidence interval (CI), 30-62 %) and 5-year overall survival was 59 % (95 % CI, 43-74 %). Fourteen of 41 patients proceeded directly to autologous transplant. GEM-P is a salvage chemotherapy with relatively high response rates, leading to successful transplantation in appropriate patients, in the treatment of relapsed or refractory HL.","[{'text': 'GEM', 'type': 'Chemical', 'start': 0, 'end': 3, 'mesh': 'C056507'}, {'text': 'Hodgkin lymphoma', 'type': 'Disease', 'start': 58, 'end': 74, 'mesh': 'D006689'}, {'text': 'Hodgkin lymphoma', 'type': 'Disease', 'start': 76, 'end': 92, 'mesh': 'D006689'}, {'text': 'HL', 'type': 'Disease', 'start': 94, 'end': 96, 'mesh': 'D006689'}, {'text': 'malignancy', 'type': 'Disease', 'start': 129, 'end': 139, 'mesh': 'D009369'}, {'text': 'toxicity', 'type': 'Disease', 'start': 429, 'end': 437, 'mesh': 'D064420'}, {'text': 'Gemcitabine', 'type': 'Chemical', 'start': 439, 'end': 450, 'mesh': 'C056507'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 455, 'end': 464, 'mesh': 'D002945'}, {'text': 'HL', 'type': 'Disease', 'start': 482, 'end': 484, 'mesh': 'D006689'}, {'text': 'toxicity', 'type': 'Disease', 'start': 502, 'end': 510, 'mesh': 'D064420'}, {'text': 'HL', 'type': 'Disease', 'start': 676, 'end': 678, 'mesh': 'D006689'}, {'text': 'gemcitabine', 'type': 'Chemical', 'start': 692, 'end': 703, 'mesh': 'C056507'}, {'text': 'methylprednisolone', 'type': 'Chemical', 'start': 740, 'end': 758, 'mesh': 'D008775'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 778, 'end': 787, 'mesh': 'D002945'}, {'text': 'GEM', 'type': 'Chemical', 'start': 820, 'end': 823, 'mesh': 'C056507'}, {'text': 'toxicity', 'type': 'Disease', 'start': 878, 'end': 886, 'mesh': 'D064420'}, {'text': 'GEM', 'type': 'Chemical', 'start': 1004, 'end': 1007, 'mesh': 'C056507'}, {'text': 'GEM', 'type': 'Chemical', 'start': 1105, 'end': 1108, 'mesh': 'C056507'}, {'text': 'GEM', 'type': 'Chemical', 'start': 1207, 'end': 1210, 'mesh': 'C056507'}, {'text': 'toxicities', 'type': 'Disease', 'start': 1419, 'end': 1429, 'mesh': 'D064420'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 1451, 'end': 1462, 'mesh': 'D009503'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 1472, 'end': 1488, 'mesh': 'D013921'}, {'text': 'GEM', 'type': 'Chemical', 'start': 1530, 'end': 1533, 'mesh': 'C056507'}, {'text': 'GEM', 'type': 'Chemical', 'start': 1561, 'end': 1564, 'mesh': 'C056507'}, {'text': 'GEM', 'type': 'Chemical', 'start': 1777, 'end': 1780, 'mesh': 'C056507'}, {'text': 'HL', 'type': 'Disease', 'start': 1952, 'end': 1954, 'mesh': 'D006689'}]"
+1025,24190587,Basal functioning of the hypothalamic-pituitary-adrenal (HPA) axis and psychological distress in recreational ecstasy polydrug users.,"RATIONALE: Ecstasy (MDMA) is a psychostimulant drug which is increasingly associated with psychobiological dysfunction. While some recent studies suggest acute changes in neuroendocrine function, less is known about long-term changes in HPA functionality in recreational users. OBJECTIVES: The current study is the first to explore the effects of ecstasy-polydrug use on psychological distress and basal functioning of the HPA axis through assessing the secretion of cortisol across the diurnal period. METHOD: Seventy-six participants (21 nonusers, 29 light ecstasy-polydrug users, 26 heavy ecstasy-polydrug users) completed a substance use inventory and measures of psychological distress at baseline, then two consecutive days of cortisol sampling (on awakening, 30 min post awakening, between 1400 and 1600 hours and pre bedtime). On day 2, participants also attended the laboratory to complete a 20-min multitasking stressor. RESULTS: Both user groups exhibited significantly greater levels of anxiety and depression than nonusers. On day 1, all participants exhibited a typical cortisol profile, though light users had significantly elevated levels pre-bed. On day 2, heavy users demonstrated elevated levels upon awakening and all ecstasy-polydrug users demonstrated elevated pre-bed levels compared to non-users. Significant between group differences were also observed in afternoon cortisol levels and in overall cortisol secretion across the day. CONCLUSIONS: The increases in anxiety and depression are in line with previous observations in recreational ecstasy-polydrug users. Dysregulated diurnal cortisol may be indicative of inappropriate anticipation of forthcoming demands and hypersecretion may lead to the increased psychological and physical morbidity associated with heavy recreational use of ecstasy.","[{'text': 'ecstasy', 'type': 'Chemical', 'start': 110, 'end': 117, 'mesh': 'D018817'}, {'text': 'Ecstasy', 'type': 'Chemical', 'start': 145, 'end': 152, 'mesh': 'D018817'}, {'text': 'MDMA', 'type': 'Chemical', 'start': 154, 'end': 158, 'mesh': 'D018817'}, {'text': 'psychobiological dysfunction', 'type': 'Disease', 'start': 224, 'end': 252, 'mesh': 'D008107'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 481, 'end': 488, 'mesh': 'D018817'}, {'text': 'cortisol', 'type': 'Chemical', 'start': 601, 'end': 609, 'mesh': 'D006854'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 693, 'end': 700, 'mesh': 'D018817'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 726, 'end': 733, 'mesh': 'D018817'}, {'text': 'cortisol', 'type': 'Chemical', 'start': 867, 'end': 875, 'mesh': 'D006854'}, {'text': 'anxiety', 'type': 'Disease', 'start': 1133, 'end': 1140, 'mesh': 'D001008'}, {'text': 'depression', 'type': 'Disease', 'start': 1145, 'end': 1155, 'mesh': 'D003866'}, {'text': 'cortisol', 'type': 'Chemical', 'start': 1218, 'end': 1226, 'mesh': 'D006854'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 1372, 'end': 1379, 'mesh': 'D018817'}, {'text': 'cortisol', 'type': 'Chemical', 'start': 1525, 'end': 1533, 'mesh': 'D006854'}, {'text': 'cortisol', 'type': 'Chemical', 'start': 1556, 'end': 1564, 'mesh': 'D006854'}, {'text': 'anxiety', 'type': 'Disease', 'start': 1621, 'end': 1628, 'mesh': 'D001008'}, {'text': 'depression', 'type': 'Disease', 'start': 1633, 'end': 1643, 'mesh': 'D003866'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 1699, 'end': 1706, 'mesh': 'D018817'}, {'text': 'cortisol', 'type': 'Chemical', 'start': 1744, 'end': 1752, 'mesh': 'D006854'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 1948, 'end': 1955, 'mesh': 'D018817'}]"
+1026,24209900,Ifosfamide related encephalopathy: the need for a timely EEG evaluation.,"BACKGROUND: Ifosfamide is an alkylating agent useful in the treatment of a wide range of cancers including sarcomas, lymphoma, gynecologic and testicular cancers. Encephalopathy has been reported in 10-40% of patients receiving high-dose IV ifosfamide. OBJECTIVE: To highlight the role of electroencephalogram (EEG) in the early detection and management of ifosfamide related encephalopathy. METHODS: Retrospective chart review including clinical data and EEG recordings was done on five patients, admitted to MD Anderson Cancer Center between years 2009 and 2012, who developed ifosfamide related acute encephalopathy. RESULTS: All five patients experienced symptoms of encephalopathy soon after (within 12 h-2 days) receiving ifosfamide. Two patients developed generalized convulsions while one patient developed continuous non-convulsive status epilepticus (NCSE) that required ICU admission and intubation. Initial EEG showed epileptiform discharges in three patients; run of triphasic waves in one patient and moderate degree diffuse generalized slowing. Mixed pattern with the presence of both sharps and triphasic waves were also noted. Repeat EEGs within 24_h of symptom onset showed marked improvement that was correlated with clinical improvement. CONCLUSIONS: Severity of ifosfamide related encephalopathy correlates with EEG changes. We suggest a timely EEG evaluation for patients receiving ifosfamide who develop features of encephalopathy.","[{'text': 'Ifosfamide', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D007069'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 19, 'end': 33, 'mesh': 'D001927'}, {'text': 'Ifosfamide', 'type': 'Chemical', 'start': 85, 'end': 95, 'mesh': 'D007069'}, {'text': 'cancers', 'type': 'Disease', 'start': 162, 'end': 169, 'mesh': 'D009369'}, {'text': 'sarcomas', 'type': 'Disease', 'start': 180, 'end': 188, 'mesh': 'D012509'}, {'text': 'lymphoma', 'type': 'Disease', 'start': 190, 'end': 198, 'mesh': 'D008223'}, {'text': 'gynecologic and testicular cancers', 'type': 'Disease', 'start': 200, 'end': 234, 'mesh': 'D009369'}, {'text': 'Encephalopathy', 'type': 'Disease', 'start': 236, 'end': 250, 'mesh': 'D001927'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 314, 'end': 324, 'mesh': 'D007069'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 430, 'end': 440, 'mesh': 'D007069'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 449, 'end': 463, 'mesh': 'D001927'}, {'text': 'Cancer', 'type': 'Disease', 'start': 595, 'end': 601, 'mesh': 'D009369'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 652, 'end': 662, 'mesh': 'D007069'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 677, 'end': 691, 'mesh': 'D001927'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 744, 'end': 758, 'mesh': 'D001927'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 801, 'end': 811, 'mesh': 'D007069'}, {'text': 'convulsions', 'type': 'Disease', 'start': 848, 'end': 859, 'mesh': 'D012640'}, {'text': 'non-convulsive status epilepticus', 'type': 'Disease', 'start': 899, 'end': 932, 'mesh': 'D013226'}, {'text': 'NCSE', 'type': 'Disease', 'start': 934, 'end': 938, 'mesh': 'D013226'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 1356, 'end': 1366, 'mesh': 'D007069'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 1375, 'end': 1389, 'mesh': 'D001927'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 1477, 'end': 1487, 'mesh': 'D007069'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 1512, 'end': 1526, 'mesh': 'D001927'}]"
+1027,24220752,Incidence of contrast-induced nephropathy in hospitalised patients with cancer.,"OBJECTIVES: To determine the frequency of and possible factors related to contrast-induced nephropathy (CIN) in hospitalised patients with cancer. METHODS: Ninety adult patients were enrolled. Patients with risk factors for acute renal failure were excluded. Blood samples were examined the day before contrast-enhanced computed tomography (CT) and serially for 3 days thereafter. CIN was defined as an increase in serum creatinine (Cr) of 0.5 mg/dl or more, or elevation of Cr to 25 % over baseline. Relationships between CIN and possible risk factors were investigated. RESULTS: CIN was detected in 18/90 (20 %) patients. CIN developed in 25.5 % patients who underwent chemotherapy and in 11 % patients who did not (P = 0.1). CIN more frequently developed in patients who had undergone CT within 45 days after the last chemotherapy (P = 0.005); it was also an independent risk factor (P = 0.017). CIN was significantly more after treatment with bevacizumab/irinotecan (P = 0.021) and in patients with hypertension (P = 0.044). CONCLUSIONS: The incidence of CIN after CT in hospitalised oncological patients was 20 %. CIN developed 4.5-times more frequently in patients with cancer who had undergone recent chemotherapy. Hypertension and the combination of bevacizumab/irinotecan may be additional risk factors for CIN development. KEY POINTS: . Contrast-induced nephropathy (CIN) is a concern for oncological patients undergoing CT. . CIN occurs more often when CT is performed <45 days after chemotherapy. . Hypertension and treatment with bevacizumab appear to be additional risk factors.","[{'text': 'contrast', 'type': 'Chemical', 'start': 13, 'end': 21, 'mesh': 'D003287'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 30, 'end': 41, 'mesh': 'D007674'}, {'text': 'cancer', 'type': 'Disease', 'start': 72, 'end': 78, 'mesh': 'D009369'}, {'text': 'contrast', 'type': 'Chemical', 'start': 154, 'end': 162, 'mesh': 'D003287'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 171, 'end': 182, 'mesh': 'D007674'}, {'text': 'cancer', 'type': 'Disease', 'start': 219, 'end': 225, 'mesh': 'D009369'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 304, 'end': 323, 'mesh': 'D058186'}, {'text': 'contrast', 'type': 'Chemical', 'start': 382, 'end': 390, 'mesh': 'D003287'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 501, 'end': 511, 'mesh': 'D003404'}, {'text': 'Cr', 'type': 'Chemical', 'start': 513, 'end': 515, 'mesh': 'D002857'}, {'text': 'Cr', 'type': 'Chemical', 'start': 555, 'end': 557, 'mesh': 'D002857'}, {'text': 'bevacizumab', 'type': 'Chemical', 'start': 1027, 'end': 1038, 'mesh': '-1'}, {'text': 'irinotecan', 'type': 'Chemical', 'start': 1039, 'end': 1049, 'mesh': 'C051890'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1083, 'end': 1095, 'mesh': 'D006973'}, {'text': 'cancer', 'type': 'Disease', 'start': 1256, 'end': 1262, 'mesh': 'D009369'}, {'text': 'Hypertension', 'type': 'Disease', 'start': 1302, 'end': 1314, 'mesh': 'D006973'}, {'text': 'bevacizumab', 'type': 'Chemical', 'start': 1338, 'end': 1349, 'mesh': '-1'}, {'text': 'irinotecan', 'type': 'Chemical', 'start': 1350, 'end': 1360, 'mesh': 'C051890'}, {'text': 'Contrast', 'type': 'Chemical', 'start': 1427, 'end': 1435, 'mesh': 'D003287'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1444, 'end': 1455, 'mesh': 'D007674'}, {'text': 'Hypertension', 'type': 'Disease', 'start': 1591, 'end': 1603, 'mesh': 'D006973'}, {'text': 'bevacizumab', 'type': 'Chemical', 'start': 1623, 'end': 1634, 'mesh': '-1'}]"
+1028,24234943,Syndrome of inappropriate antidiuretic hormone secretion associated with desvenlafaxine.,"OBJECTIVE: To report a case of syndrome of inappropriate anti-diuretic hormone (SIADH) secretion associated with desvenlafaxine. CASE SUMMARY: A 57-year old female with hyponatraemia. Her medications included desvenlafaxine, and symptoms included nausea, anxiety and confusion. The serum sodium at this time was 120 mmol/L, serum osmolality was 263 mosmol/kg, urine osmolality 410 mosmol/kg and urine sodium 63 mmol/L, consistent with a diagnosis of SIADH. Desvenlafaxine was ceased and fluid restriction implemented. After 4 days the sodium increased to 128 mmol/L and fluid restriction was relaxed. During her further 3 weeks inpatient admission the serum sodium ranged from 134 to 137 mmol/L during treatment with mirtazapine. DISCUSSION: SIADH has been widely reported with a range of antidepressants. This case report suggests that desvenlafaxine might cause clinically significant hyponatremia. CONCLUSIONS: Clinicians should be aware of the potential for antidepressants to cause hyponatremia,and take appropriate corrective action where necessary.","[{'text': 'Syndrome of inappropriate antidiuretic hormone', 'type': 'Disease', 'start': 0, 'end': 46, 'mesh': 'D007177'}, {'text': 'desvenlafaxine', 'type': 'Chemical', 'start': 73, 'end': 87, 'mesh': 'C086816'}, {'text': 'syndrome of inappropriate anti-diuretic hormone', 'type': 'Disease', 'start': 120, 'end': 167, 'mesh': 'D007177'}, {'text': 'SIADH', 'type': 'Disease', 'start': 169, 'end': 174, 'mesh': 'D007177'}, {'text': 'desvenlafaxine', 'type': 'Chemical', 'start': 202, 'end': 216, 'mesh': 'C086816'}, {'text': 'hyponatraemia', 'type': 'Disease', 'start': 258, 'end': 271, 'mesh': 'D007010'}, {'text': 'desvenlafaxine', 'type': 'Chemical', 'start': 298, 'end': 312, 'mesh': 'C086816'}, {'text': 'nausea', 'type': 'Disease', 'start': 336, 'end': 342, 'mesh': 'D009325'}, {'text': 'anxiety', 'type': 'Disease', 'start': 344, 'end': 351, 'mesh': 'D001008'}, {'text': 'confusion', 'type': 'Disease', 'start': 356, 'end': 365, 'mesh': 'D003221'}, {'text': 'sodium', 'type': 'Chemical', 'start': 377, 'end': 383, 'mesh': 'D012964'}, {'text': 'sodium', 'type': 'Chemical', 'start': 490, 'end': 496, 'mesh': 'D012964'}, {'text': 'SIADH', 'type': 'Disease', 'start': 539, 'end': 544, 'mesh': 'D007177'}, {'text': 'Desvenlafaxine', 'type': 'Chemical', 'start': 546, 'end': 560, 'mesh': 'C086816'}, {'text': 'sodium', 'type': 'Chemical', 'start': 624, 'end': 630, 'mesh': 'D012964'}, {'text': 'sodium', 'type': 'Chemical', 'start': 747, 'end': 753, 'mesh': 'D012964'}, {'text': 'mirtazapine', 'type': 'Chemical', 'start': 806, 'end': 817, 'mesh': 'C035133'}, {'text': 'SIADH', 'type': 'Disease', 'start': 831, 'end': 836, 'mesh': 'D007177'}, {'text': 'desvenlafaxine', 'type': 'Chemical', 'start': 926, 'end': 940, 'mesh': 'C086816'}, {'text': 'hyponatremia', 'type': 'Disease', 'start': 976, 'end': 988, 'mesh': 'D007010'}, {'text': 'hyponatremia', 'type': 'Disease', 'start': 1076, 'end': 1088, 'mesh': 'D007010'}]"
+1029,24275640,Oxidative stress on cardiotoxicity after treatment with single and multiple doses of doxorubicin.,"The mechanism of doxorubicin (DOX)-induced cardiotoxicity remains controversial. Wistar rats (n = 66) received DOX injections intraperitoneally and were randomly assigned to 2 experimental protocols: (1) rats were killed before (-24 h, n = 8) and 24 h after (+24 h, n = 8) a single dose of DOX (4 mg/kg body weight) to determine the DOX acute effect and (2) rats (n = 58) received 4 injections of DOX (4 mg/kg body weight/week) and were killed before the first injection (M0) and 1 week after each injection (M1, M2, M3, and M4) to determine the chronological effects. Animals used at M0 (n = 8) were also used at moment -24 h of acute study. Cardiac total antioxidant performance (TAP), DNA damage, and morphology analyses were carried out at each time point. Single dose of DOX was associated with increased cardiac disarrangement, necrosis, and DNA damage (strand breaks (SBs) and oxidized pyrimidines) and decreased TAP. The chronological study showed an effect of a cumulative dose on body weight (R = -0.99, p = 0.011), necrosis (R = 1.00, p = 0.004), TAP (R = 0.95, p = 0.049), and DNA SBs (R = -0.95, p = 0.049). DNA SBs damage was negatively associated with TAP (R = -0.98, p = 0.018), and necrosis (R = -0.97, p = 0.027). Our results suggest that oxidative damage is associated with acute cardiotoxicity induced by a single dose of DOX only. Increased resistance to the oxidative stress is plausible for the multiple dose of DOX. Thus, different mechanisms may be involved in acute toxicity versus chronic toxicity.","[{'text': 'cardiotoxicity', 'type': 'Disease', 'start': 20, 'end': 34, 'mesh': 'D066126'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 85, 'end': 96, 'mesh': 'D004317'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 115, 'end': 126, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 128, 'end': 131, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 141, 'end': 155, 'mesh': 'D066126'}, {'text': 'DOX', 'type': 'Chemical', 'start': 209, 'end': 212, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 388, 'end': 391, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 431, 'end': 434, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 495, 'end': 498, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 874, 'end': 877, 'mesh': 'D004317'}, {'text': 'cardiac disarrangement', 'type': 'Disease', 'start': 908, 'end': 930, 'mesh': 'D006331'}, {'text': 'necrosis', 'type': 'Disease', 'start': 932, 'end': 940, 'mesh': 'D009336'}, {'text': 'necrosis', 'type': 'Disease', 'start': 1124, 'end': 1132, 'mesh': 'D009336'}, {'text': 'necrosis', 'type': 'Disease', 'start': 1297, 'end': 1305, 'mesh': 'D009336'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1397, 'end': 1411, 'mesh': 'D066126'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1440, 'end': 1443, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1533, 'end': 1536, 'mesh': 'D004317'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1590, 'end': 1598, 'mesh': 'D064420'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1614, 'end': 1622, 'mesh': 'D064420'}]"
+1030,24283660,Tacrolimus-related seizure after pediatric liver transplantation--a single-center experience.,"To identify the risk factors for new-onset seizures after pediatric LT and to assess their clinical implications and long-term prognosis. The clinical and laboratory data of 27 consecutive children who underwent LT from January 2007 to December 2010 in our center were analyzed retrospectively. Patients were divided into seizures group and a non-seizures group. Pre-operative, intra-operative, and post-operative data were collected. Seizures occurred in four children, an incidence of 14.8%. All exhibited generalized tonic-clonic seizures within the first two wk after LT. Univariate analysis showed that the risk factors associated with seizures after pediatric LT included gender, pediatric end-stage liver disease score before surgery, Child-Pugh score before surgery, serum total bilirubin after surgery, and trough TAC level. Multivariate analysis showed that trough TAC level was the only independent risk factor associated with the seizures. All children who experienced seizures survived with good graft function and remained seizure-free without anti-epileptic drugs over a mean follow-up period of 33.7 + 14.6 months. High trough TAC level was the predominant factor that contributed to seizures in the early post-operative period after pediatric LT. High PELD and Child-Pugh scores before LT and high post-operative serum Tbil may be contributory risk factors for TAC-related seizures.","[{'text': 'Tacrolimus', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D016559'}, {'text': 'seizure', 'type': 'Disease', 'start': 19, 'end': 26, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 137, 'end': 145, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 416, 'end': 424, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 441, 'end': 449, 'mesh': 'D012640'}, {'text': 'Seizures', 'type': 'Disease', 'start': 529, 'end': 537, 'mesh': 'D012640'}, {'text': 'tonic-clonic seizures', 'type': 'Disease', 'start': 614, 'end': 635, 'mesh': 'D004830'}, {'text': 'seizures', 'type': 'Disease', 'start': 735, 'end': 743, 'mesh': 'D012640'}, {'text': 'end-stage liver disease', 'type': 'Disease', 'start': 790, 'end': 813, 'mesh': 'D058625'}, {'text': 'bilirubin', 'type': 'Chemical', 'start': 881, 'end': 890, 'mesh': 'D001663'}, {'text': 'TAC', 'type': 'Chemical', 'start': 917, 'end': 920, 'mesh': 'D016559'}, {'text': 'TAC', 'type': 'Chemical', 'start': 969, 'end': 972, 'mesh': 'D016559'}, {'text': 'seizures', 'type': 'Disease', 'start': 1036, 'end': 1044, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 1075, 'end': 1083, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 1131, 'end': 1138, 'mesh': 'D012640'}, {'text': 'epileptic', 'type': 'Disease', 'start': 1157, 'end': 1166, 'mesh': 'D004827'}, {'text': 'TAC', 'type': 'Chemical', 'start': 1237, 'end': 1240, 'mesh': 'D016559'}, {'text': 'seizures', 'type': 'Disease', 'start': 1294, 'end': 1302, 'mesh': 'D012640'}, {'text': 'TAC', 'type': 'Chemical', 'start': 1472, 'end': 1475, 'mesh': 'D016559'}, {'text': 'seizures', 'type': 'Disease', 'start': 1484, 'end': 1492, 'mesh': 'D012640'}]"
+1031,24284476,The flavonoid apigenin delays forgetting of passive avoidance conditioning in rats.,"The present experiments were performed to study the effect of the flavonoid apigenin (20 mg/kg intraperitoneally (i.p.), 1 h before acquisition), on 24 h retention performance and forgetting of a step-through passive avoidance task, in young male Wistar rats. There were no differences between saline- and apigenin-treated groups in the 24 h retention trial. Furthermore, apigenin did not prevent the amnesia induced by scopolamine (1mg/kg, i.p., 30 min before the acquisition). The saline- and apigenin-treated rats that did not step through into the dark compartment during the cut-off time (540 s) were retested weekly for up to eight weeks. In the saline treated group, the first significant decline in passive avoidance response was observed at four weeks, and complete memory loss was found five weeks after the acquisition of the passive avoidance task. At the end of the experimental period, 60% of the animals treated with apigenin still did not step through. These data suggest that 1) apigenin delays the long-term forgetting but did not modulate the 24 h retention of fear memory and 2) the obtained beneficial effect of apigenin on the passive avoidance conditioning is mediated by mechanisms that do not implicate its action on the muscarinic cholinergic system.","[{'text': 'flavonoid', 'type': 'Chemical', 'start': 4, 'end': 13, 'mesh': 'D005419'}, {'text': 'apigenin', 'type': 'Chemical', 'start': 14, 'end': 22, 'mesh': 'D047310'}, {'text': 'flavonoid', 'type': 'Chemical', 'start': 150, 'end': 159, 'mesh': 'D005419'}, {'text': 'apigenin', 'type': 'Chemical', 'start': 160, 'end': 168, 'mesh': 'D047310'}, {'text': 'apigenin', 'type': 'Chemical', 'start': 390, 'end': 398, 'mesh': 'D047310'}, {'text': 'apigenin', 'type': 'Chemical', 'start': 456, 'end': 464, 'mesh': 'D047310'}, {'text': 'amnesia', 'type': 'Disease', 'start': 485, 'end': 492, 'mesh': 'D000647'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 504, 'end': 515, 'mesh': 'D012601'}, {'text': 'apigenin', 'type': 'Chemical', 'start': 579, 'end': 587, 'mesh': 'D047310'}, {'text': 'memory loss', 'type': 'Disease', 'start': 859, 'end': 870, 'mesh': 'D008569'}, {'text': 'apigenin', 'type': 'Chemical', 'start': 1016, 'end': 1024, 'mesh': 'D047310'}, {'text': 'apigenin', 'type': 'Chemical', 'start': 1080, 'end': 1088, 'mesh': 'D047310'}, {'text': 'apigenin', 'type': 'Chemical', 'start': 1217, 'end': 1225, 'mesh': 'D047310'}]"
+1032,24309294,Cholecystokinin-octapeptide restored morphine-induced hippocampal long-term potentiation impairment in rats.,"Cholecystokinin-octapeptide (CCK-8), which is a typical brain-gut peptide, exerts a wide range of biological activities on the central nervous system. We have previously reported that CCK-8 significantly alleviated morphine-induced amnesia and reversed spine density decreases in the CA1 region of the hippocampus in morphine-treated animals. Here, we investigated the effects of CCK-8 on long-term potentiation (LTP) in the lateral perforant path (LPP)-granule cell synapse of rat dentate gyrus (DG) in acute saline or morphine-treated rats. Population spikes (PS), which were evoked by stimulation of the LPP, were recorded in the DG region. Acute morphine (30mg/kg, s.c.) treatment significantly attenuated hippocampal LTP and CCK-8 (1ug, i.c.v.) restored the amplitude of PS that was attenuated by morphine injection. Furthermore, microinjection of CCK-8 (0.1 and 1ug, i.c.v.) also significantly augmented hippocampal LTP in saline-treated (1ml/kg, s.c.) rats. Pre-treatment of the CCK2 receptor antagonist L-365,260 (10ug, i.c.v) reversed the effects of CCK-8, but the CCK1 receptor antagonist L-364,718 (10ug, i.c.v) did not. The present results demonstrate that CCK-8 attenuates the effect of morphine on hippocampal LTP through CCK2 receptors and suggest an ameliorative function of CCK-8 on morphine-induced memory impairment.","[{'text': 'Cholecystokinin-octapeptide', 'type': 'Chemical', 'start': 0, 'end': 27, 'mesh': 'D012844'}, {'text': 'morphine', 'type': 'Chemical', 'start': 37, 'end': 45, 'mesh': 'D009020'}, {'text': 'Cholecystokinin-octapeptide', 'type': 'Chemical', 'start': 109, 'end': 136, 'mesh': 'D012844'}, {'text': 'CCK-8', 'type': 'Chemical', 'start': 138, 'end': 143, 'mesh': 'D012844'}, {'text': 'CCK-8', 'type': 'Chemical', 'start': 293, 'end': 298, 'mesh': 'D012844'}, {'text': 'morphine', 'type': 'Chemical', 'start': 324, 'end': 332, 'mesh': 'D009020'}, {'text': 'amnesia', 'type': 'Disease', 'start': 341, 'end': 348, 'mesh': 'D000647'}, {'text': 'morphine', 'type': 'Chemical', 'start': 426, 'end': 434, 'mesh': 'D009020'}, {'text': 'CCK-8', 'type': 'Chemical', 'start': 489, 'end': 494, 'mesh': 'D012844'}, {'text': 'morphine', 'type': 'Chemical', 'start': 629, 'end': 637, 'mesh': 'D009020'}, {'text': 'morphine', 'type': 'Chemical', 'start': 759, 'end': 767, 'mesh': 'D009020'}, {'text': 'CCK-8', 'type': 'Chemical', 'start': 839, 'end': 844, 'mesh': 'D012844'}, {'text': 'morphine', 'type': 'Chemical', 'start': 911, 'end': 919, 'mesh': 'D009020'}, {'text': 'CCK-8', 'type': 'Chemical', 'start': 962, 'end': 967, 'mesh': 'D012844'}, {'text': 'CCK-8', 'type': 'Chemical', 'start': 1168, 'end': 1173, 'mesh': 'D012844'}, {'text': 'CCK-8', 'type': 'Chemical', 'start': 1278, 'end': 1283, 'mesh': 'D012844'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1309, 'end': 1317, 'mesh': 'D009020'}, {'text': 'CCK-8', 'type': 'Chemical', 'start': 1400, 'end': 1405, 'mesh': 'D012844'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1409, 'end': 1417, 'mesh': 'D009020'}, {'text': 'memory impairment', 'type': 'Disease', 'start': 1426, 'end': 1443, 'mesh': 'D008569'}]"
+1033,24333387,Glial activation and post-synaptic neurotoxicity: the key events in Streptozotocin (ICV) induced memory impairment in rats.,"In the present study the role of glial activation and post synaptic toxicity in ICV Streptozotocin (STZ) induced memory impaired rats was explored. In experiment set up 1: Memory deficit was found in Morris water maze test on 14-16 days after STZ (ICV; 3mg/Kg) administration. STZ causes increased expression of GFAP, CD11b and TNF-a indicating glial activation and neuroinflammation. STZ also significantly increased the level of ROS, nitrite, Ca(2+) and reduced the mitochondrial activity in synaptosomal preparation illustrating free radical generation and excitotoxicity. Increased expression and activity of Caspase-3 was also observed in STZ treated rat which specify apoptotic cell death in hippocampus and cortex. STZ treatment showed decrease expression of post synaptic markers CaMKIIa and PSD-95, while, expression of pre synaptic markers (synaptophysin and SNAP-25) remains unaltered indicating selective post synaptic neurotoxicity. Oral treatment with Memantine (10mg/kg) and Ibuprofen (50 mg/kg) daily for 13 days attenuated STZ induced glial activation, apoptotic cell death and post synaptic neurotoxicity in rat brain. Further, in experiment set up 2: where memory function was not affected i.e. 7-9 days after STZ treatment. The level of GFAP, CD11b, TNF-a, ROS and nitrite levels were increased. On the other hand, apoptotic marker, synaptic markers, mitochondrial activity and Ca(2+) levels remained unaffected. Collective data indicates that neuroinflammatory process and oxidative stress occurs earlier to apoptosis and does not affect memory function. Present study clearly suggests that glial activation and post synaptic neurotoxicity are the key factors in STZ induced memory impairment and neuronal cell death.","[{'text': 'neurotoxicity', 'type': 'Disease', 'start': 35, 'end': 48, 'mesh': 'D020258'}, {'text': 'Streptozotocin', 'type': 'Chemical', 'start': 68, 'end': 82, 'mesh': 'D013311'}, {'text': 'memory impairment', 'type': 'Disease', 'start': 97, 'end': 114, 'mesh': 'D008569'}, {'text': 'toxicity', 'type': 'Disease', 'start': 192, 'end': 200, 'mesh': 'D064420'}, {'text': 'Streptozotocin', 'type': 'Chemical', 'start': 208, 'end': 222, 'mesh': 'D013311'}, {'text': 'STZ', 'type': 'Chemical', 'start': 224, 'end': 227, 'mesh': 'D013311'}, {'text': 'memory impaired', 'type': 'Disease', 'start': 237, 'end': 252, 'mesh': 'D008569'}, {'text': 'Memory deficit', 'type': 'Disease', 'start': 296, 'end': 310, 'mesh': 'D008569'}, {'text': 'STZ', 'type': 'Chemical', 'start': 367, 'end': 370, 'mesh': 'D013311'}, {'text': 'STZ', 'type': 'Chemical', 'start': 401, 'end': 404, 'mesh': 'D013311'}, {'text': 'neuroinflammation', 'type': 'Disease', 'start': 490, 'end': 507, 'mesh': 'D007249'}, {'text': 'STZ', 'type': 'Chemical', 'start': 509, 'end': 512, 'mesh': 'D013311'}, {'text': 'nitrite', 'type': 'Chemical', 'start': 560, 'end': 567, 'mesh': 'D009573'}, {'text': 'Ca', 'type': 'Chemical', 'start': 569, 'end': 571, 'mesh': 'D002118'}, {'text': 'excitotoxicity', 'type': 'Disease', 'start': 684, 'end': 698, 'mesh': 'D064420'}, {'text': 'STZ', 'type': 'Chemical', 'start': 768, 'end': 771, 'mesh': 'D013311'}, {'text': 'STZ', 'type': 'Chemical', 'start': 846, 'end': 849, 'mesh': 'D013311'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 1055, 'end': 1068, 'mesh': 'D020258'}, {'text': 'Memantine', 'type': 'Chemical', 'start': 1090, 'end': 1099, 'mesh': 'D008559'}, {'text': 'Ibuprofen', 'type': 'Chemical', 'start': 1114, 'end': 1123, 'mesh': 'D007052'}, {'text': 'STZ', 'type': 'Chemical', 'start': 1164, 'end': 1167, 'mesh': 'D013311'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 1233, 'end': 1246, 'mesh': 'D020258'}, {'text': 'STZ', 'type': 'Chemical', 'start': 1353, 'end': 1356, 'mesh': 'D013311'}, {'text': 'nitrite', 'type': 'Chemical', 'start': 1409, 'end': 1416, 'mesh': 'D009573'}, {'text': 'Ca', 'type': 'Chemical', 'start': 1522, 'end': 1524, 'mesh': 'D002118'}, {'text': 'neuroinflammatory', 'type': 'Disease', 'start': 1588, 'end': 1605, 'mesh': 'D007249'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 1771, 'end': 1784, 'mesh': 'D020258'}, {'text': 'STZ', 'type': 'Chemical', 'start': 1808, 'end': 1811, 'mesh': 'D013311'}, {'text': 'memory impairment', 'type': 'Disease', 'start': 1820, 'end': 1837, 'mesh': 'D008569'}]"
+1034,24341598,Comparison of effects of isotonic sodium chloride with diltiazem in prevention of contrast-induced nephropathy.,"INTRODUCTION AND OBJECTIVE: Contrast-induced nephropathy (CIN) significantly increases the morbidity and mortality of patients. The aim of this study is to investigate and compare the protective effects of isotonic sodium chloride with sodium bicarbonate infusion and isotonic sodium chloride infusion with diltiazem, a calcium channel blocker, in preventing CIN. MATERIALS AND METHODS: Our study included patients who were administered 30-60 mL of iodinated contrast agent for percutaneous coronary angiography (PCAG), all with creatinine values between 1.1 and 3.1 mg/dL. Patients were divided into three groups and each group had 20 patients. The first group of patients was administered isotonic sodium chloride; the second group was administered a solution that of 5% dextrose and sodium bicarbonate, while the third group was administered isotonic sodium chloride before and after the contrast injection. The third group received an additional injection of diltiazem the day before and first 2 days after the contrast injection. All of the patients' plasma blood urea nitrogen (BUN) and creatinine levels were measured on the second and seventh day after the administration of intravenous contrast material. RESULTS: The basal creatinine levels were similar for all three groups (p > 0.05). Among a total of 60 patients included in the study, 16 patients developed acute renal failure (ARF) on the second day after contrast material was injected (26.6%). The number of patients who developed ARF on the second day after the injection in the first group was five (25%), in the second group was six (30%) and the third group was five (25%) (p > 0.05). CONCLUSION: There was no significant difference between isotonic sodium chloride, sodium bicarbonate and isotonic sodium chloride with diltiazem application in prevention of CIN.","[{'text': 'sodium chloride', 'type': 'Chemical', 'start': 34, 'end': 49, 'mesh': 'D012965'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 55, 'end': 64, 'mesh': 'D004110'}, {'text': 'contrast', 'type': 'Chemical', 'start': 82, 'end': 90, 'mesh': 'D003287'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 99, 'end': 110, 'mesh': 'D007674'}, {'text': 'Contrast', 'type': 'Chemical', 'start': 140, 'end': 148, 'mesh': 'D003287'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 157, 'end': 168, 'mesh': 'D007674'}, {'text': 'sodium chloride', 'type': 'Chemical', 'start': 327, 'end': 342, 'mesh': 'D012965'}, {'text': 'sodium bicarbonate', 'type': 'Chemical', 'start': 348, 'end': 366, 'mesh': 'D017693'}, {'text': 'sodium chloride', 'type': 'Chemical', 'start': 389, 'end': 404, 'mesh': 'D012965'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 419, 'end': 428, 'mesh': 'D004110'}, {'text': 'calcium', 'type': 'Chemical', 'start': 432, 'end': 439, 'mesh': 'D002118'}, {'text': 'contrast', 'type': 'Chemical', 'start': 571, 'end': 579, 'mesh': 'D003287'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 641, 'end': 651, 'mesh': 'D003404'}, {'text': 'sodium chloride', 'type': 'Chemical', 'start': 812, 'end': 827, 'mesh': 'D012965'}, {'text': 'dextrose', 'type': 'Chemical', 'start': 885, 'end': 893, 'mesh': 'D005947'}, {'text': 'sodium bicarbonate', 'type': 'Chemical', 'start': 898, 'end': 916, 'mesh': 'D017693'}, {'text': 'sodium chloride', 'type': 'Chemical', 'start': 966, 'end': 981, 'mesh': 'D012965'}, {'text': 'contrast', 'type': 'Chemical', 'start': 1003, 'end': 1011, 'mesh': 'D003287'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 1075, 'end': 1084, 'mesh': 'D004110'}, {'text': 'contrast', 'type': 'Chemical', 'start': 1127, 'end': 1135, 'mesh': 'D003287'}, {'text': 'blood urea nitrogen', 'type': 'Chemical', 'start': 1175, 'end': 1194, 'mesh': 'D001806'}, {'text': 'BUN', 'type': 'Chemical', 'start': 1196, 'end': 1199, 'mesh': 'D001806'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1205, 'end': 1215, 'mesh': 'D003404'}, {'text': 'contrast', 'type': 'Chemical', 'start': 1307, 'end': 1315, 'mesh': 'D003287'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1345, 'end': 1355, 'mesh': 'D003404'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 1483, 'end': 1502, 'mesh': 'D058186'}, {'text': 'ARF', 'type': 'Disease', 'start': 1504, 'end': 1507, 'mesh': 'D058186'}, {'text': 'contrast', 'type': 'Chemical', 'start': 1533, 'end': 1541, 'mesh': 'D003287'}, {'text': 'ARF', 'type': 'Disease', 'start': 1610, 'end': 1613, 'mesh': 'D058186'}, {'text': 'sodium chloride', 'type': 'Chemical', 'start': 1833, 'end': 1848, 'mesh': 'D012965'}, {'text': 'sodium bicarbonate', 'type': 'Chemical', 'start': 1850, 'end': 1868, 'mesh': 'D017693'}, {'text': 'sodium chloride', 'type': 'Chemical', 'start': 1882, 'end': 1897, 'mesh': 'D012965'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 1903, 'end': 1912, 'mesh': 'D004110'}]"
+1035,24345882,Neurocognitive and neuroradiologic central nervous system late effects in children treated on Pediatric Oncology Group (POG) P9605 (standard risk) and P9201 (lesser risk) acute lymphoblastic leukemia protocols (ACCL0131): a methotrexate consequence? A report from the Children's Oncology Group.,"Concerns about long-term methotrexate (MTX) neurotoxicity in the 1990s led to modifications in intrathecal (IT) therapy, leucovorin rescue, and frequency of systemic MTX administration in children with acute lymphoblastic leukemia. In this study, neurocognitive outcomes and neuroradiologic evidence of leukoencephalopathy were compared in children treated with intense central nervous system (CNS)-directed therapy (P9605) versus those receiving fewer CNS-directed treatment days during intensive consolidation (P9201). A total of 66 children from 16 Pediatric Oncology Group institutions with ""standard-risk"" acute lymphoblastic leukemia, 1.00 to 9.99 years at diagnosis, without evidence of CNS leukemia at diagnosis were enrolled on ACCL0131: 28 from P9201 and 38 from P9605. Magnetic resonance imaging scans and standard neuropsychological tests were performed >2.6 years after the end of treatment. Significantly more P9605 patients developed leukoencephalopathy compared with P9201 patients (68%, 95% confidence interval 49%-83% vs. 22%, 95% confidence interval 5%-44%; P=0.001) identified as late as 7.7 years after the end of treatment. Overall, 40% of patients scored <85 on either Verbal or Performance IQ. Children on both studies had significant attention problems, but P9605 children scored below average on more neurocognitive measures than those treated on P9201 (82%, 14/17 measures vs. 24%, 4/17 measures). This supports ongoing concerns about intensive MTX exposure as a major contributor to CNS late effects.","[{'text': 'acute lymphoblastic leukemia', 'type': 'Disease', 'start': 171, 'end': 199, 'mesh': 'D054198'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 224, 'end': 236, 'mesh': 'D008727'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 320, 'end': 332, 'mesh': 'D008727'}, {'text': 'MTX', 'type': 'Chemical', 'start': 334, 'end': 337, 'mesh': 'D008727'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 339, 'end': 352, 'mesh': 'D020258'}, {'text': 'MTX', 'type': 'Chemical', 'start': 461, 'end': 464, 'mesh': 'D008727'}, {'text': 'acute lymphoblastic leukemia', 'type': 'Disease', 'start': 497, 'end': 525, 'mesh': 'D054198'}, {'text': 'leukoencephalopathy', 'type': 'Disease', 'start': 598, 'end': 617, 'mesh': 'D056784'}, {'text': 'acute lymphoblastic leukemia', 'type': 'Disease', 'start': 906, 'end': 934, 'mesh': 'D054198'}, {'text': 'leukemia', 'type': 'Disease', 'start': 993, 'end': 1001, 'mesh': 'D007938'}, {'text': 'leukoencephalopathy', 'type': 'Disease', 'start': 1244, 'end': 1263, 'mesh': 'D056784'}, {'text': 'attention problems', 'type': 'Disease', 'start': 1554, 'end': 1572, 'mesh': 'D003072'}, {'text': 'MTX', 'type': 'Chemical', 'start': 1767, 'end': 1770, 'mesh': 'D008727'}]"
+1036,24434397,Tranexamic acid overdosage-induced generalized seizure in renal failure.,"We report a 45-year-old lady with chronic kidney disease stage 4 due to chronic tubulointerstial disease. She was admitted to our center for severe anemia due to menorrhagia and deterioration of renal function. She was infused three units of packed cells during a session of hemodialysis. Tranexamic acid (TNA) 1 g 8-hourly was administered to her to control bleeding per vaginum. Two hours after the sixth dose of TNA, she had an episode of generalized tonic clonic convulsions. TNA was discontinued. Investigations of the patient revealed no biochemical or structural central nervous system abnormalities that could have provoked the convulsions. She did not require any further dialytic support. She had no further episodes of convulsion till dis-charge and during the two months of follow-up. Thus, the precipitating cause of convulsions was believed to be an overdose of TNA.","[{'text': 'Tranexamic acid', 'type': 'Chemical', 'start': 0, 'end': 15, 'mesh': 'D014148'}, {'text': 'seizure', 'type': 'Disease', 'start': 47, 'end': 54, 'mesh': 'D012640'}, {'text': 'renal failure', 'type': 'Disease', 'start': 58, 'end': 71, 'mesh': 'D051437'}, {'text': 'chronic kidney disease', 'type': 'Disease', 'start': 107, 'end': 129, 'mesh': 'D051436'}, {'text': 'tubulointerstial disease', 'type': 'Disease', 'start': 153, 'end': 177, 'mesh': 'D004194'}, {'text': 'anemia', 'type': 'Disease', 'start': 221, 'end': 227, 'mesh': 'D000740'}, {'text': 'menorrhagia', 'type': 'Disease', 'start': 235, 'end': 246, 'mesh': 'D008595'}, {'text': 'deterioration of renal function', 'type': 'Disease', 'start': 251, 'end': 282, 'mesh': 'D051437'}, {'text': 'Tranexamic acid', 'type': 'Chemical', 'start': 362, 'end': 377, 'mesh': 'D014148'}, {'text': 'TNA', 'type': 'Chemical', 'start': 379, 'end': 382, 'mesh': 'D014148'}, {'text': 'bleeding', 'type': 'Disease', 'start': 432, 'end': 440, 'mesh': 'D006470'}, {'text': 'TNA', 'type': 'Chemical', 'start': 488, 'end': 491, 'mesh': 'D014148'}, {'text': 'tonic clonic convulsions', 'type': 'Disease', 'start': 527, 'end': 551, 'mesh': 'D004830'}, {'text': 'TNA', 'type': 'Chemical', 'start': 553, 'end': 556, 'mesh': 'D014148'}, {'text': 'nervous system abnormalities', 'type': 'Disease', 'start': 651, 'end': 679, 'mesh': 'D009421'}, {'text': 'convulsions', 'type': 'Disease', 'start': 709, 'end': 720, 'mesh': 'D012640'}, {'text': 'convulsion', 'type': 'Disease', 'start': 803, 'end': 813, 'mesh': 'D012640'}, {'text': 'convulsions', 'type': 'Disease', 'start': 903, 'end': 914, 'mesh': 'D012640'}, {'text': 'overdose', 'type': 'Disease', 'start': 937, 'end': 945, 'mesh': 'D062787'}, {'text': 'TNA', 'type': 'Chemical', 'start': 949, 'end': 952, 'mesh': 'D014148'}]"
+1037,24438483,Pre-treatment of bupivacaine-induced cardiovascular depression using different lipid formulations of propofol.,"BACKGROUND: Pre-treatment with lipid emulsions has been shown to increase lethal doses of bupivacaine, and the lipid content of propofol may alleviate bupivacaine-induced cardiotoxicity. The aim of this study is to investigate the effects of propofol in intralipid or medialipid emulsions on bupivacaine-induced cardiotoxicity. METHODS: Rats were anaesthetised with ketamine and were given 0.5 mg/kg/min propofol in intralipid (Group P), propofol in medialipid (Group L), or saline (Group C) over 20 min. Thereafter, 2 mg/kg/min bupivacaine 0.5% was infused. We recorded time to first dysrhythmia occurrence, respective times to 25% and 50% reduction of the heart rate (HR) and mean arterial pressure, and time to asystole and total amount of bupivacaine consumption. Blood and tissue samples were collected following asystole. RESULTS: The time to first dysrhythmia occurrence, time to 25% and 50% reductions in HR, and time to asystole were longer in Group P than the other groups. The cumulative bupivacaine dose given at those time points was higher in Group P. Plasma bupivacaine levels were significantly lower in Group P than in Group C. Bupivacaine levels in the brain and heart were significantly lower in Group P and Group L than in Group C. CONCLUSION: We conclude that pre-treatment with propofol in intralipid, compared with propofol in medialipid or saline, delayed the onset of bupivacaine-induced cardiotoxic effects as well as reduced plasma bupivacaine levels. Further studies are needed to explore tissue bupivacaine levels of propofol in medialipid and adapt these results to clinical practice.","[{'text': 'bupivacaine', 'type': 'Chemical', 'start': 17, 'end': 28, 'mesh': 'D002045'}, {'text': 'cardiovascular depression', 'type': 'Disease', 'start': 37, 'end': 62, 'mesh': 'D002318'}, {'text': 'propofol', 'type': 'Chemical', 'start': 101, 'end': 109, 'mesh': 'D015742'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 201, 'end': 212, 'mesh': 'D002045'}, {'text': 'propofol', 'type': 'Chemical', 'start': 239, 'end': 247, 'mesh': 'D015742'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 262, 'end': 273, 'mesh': 'D002045'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 282, 'end': 296, 'mesh': 'D066126'}, {'text': 'propofol', 'type': 'Chemical', 'start': 353, 'end': 361, 'mesh': 'D015742'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 403, 'end': 414, 'mesh': 'D002045'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 423, 'end': 437, 'mesh': 'D066126'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 477, 'end': 485, 'mesh': 'D007649'}, {'text': 'propofol', 'type': 'Chemical', 'start': 515, 'end': 523, 'mesh': 'D015742'}, {'text': 'propofol', 'type': 'Chemical', 'start': 549, 'end': 557, 'mesh': 'D015742'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 640, 'end': 651, 'mesh': 'D002045'}, {'text': 'dysrhythmia', 'type': 'Disease', 'start': 696, 'end': 707, 'mesh': 'D001145'}, {'text': 'asystole', 'type': 'Disease', 'start': 825, 'end': 833, 'mesh': 'D006323'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 854, 'end': 865, 'mesh': 'D002045'}, {'text': 'asystole', 'type': 'Disease', 'start': 929, 'end': 937, 'mesh': 'D006323'}, {'text': 'dysrhythmia', 'type': 'Disease', 'start': 966, 'end': 977, 'mesh': 'D001145'}, {'text': 'asystole', 'type': 'Disease', 'start': 1040, 'end': 1048, 'mesh': 'D006323'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 1110, 'end': 1121, 'mesh': 'D002045'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 1184, 'end': 1195, 'mesh': 'D002045'}, {'text': 'Bupivacaine', 'type': 'Chemical', 'start': 1256, 'end': 1267, 'mesh': 'D002045'}, {'text': 'propofol', 'type': 'Chemical', 'start': 1411, 'end': 1419, 'mesh': 'D015742'}, {'text': 'propofol', 'type': 'Chemical', 'start': 1449, 'end': 1457, 'mesh': 'D015742'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 1504, 'end': 1515, 'mesh': 'D002045'}, {'text': 'cardiotoxic', 'type': 'Disease', 'start': 1524, 'end': 1535, 'mesh': 'D066126'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 1570, 'end': 1581, 'mesh': 'D002045'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 1635, 'end': 1646, 'mesh': 'D002045'}, {'text': 'propofol', 'type': 'Chemical', 'start': 1657, 'end': 1665, 'mesh': 'D015742'}]"
+1038,24451297,Drug-Induced Acute Liver Injury Within 12 Hours After Fluvastatin Therapy.,"Although statins are generally well-tolerated drugs, recent cases of drug-induced liver injury associated with their use have been reported. A 52-year-old Chinese man reported with liver damage, which appeared 12 hours after beginning treatment with fluvastatin. Patient presented with complaints of increasing nausea, anorexia, and upper abdominal pain. His laboratory values showed elevated creatine kinase and transaminases. Testing for autoantibodies was also negative. The liver biochemistries eventually normalized within 3 weeks of stopping the fluvastatin. Therefore, when prescribing statins, the possibility of hepatic damage should be taken into account.","[{'text': 'Drug-Induced Acute Liver Injury', 'type': 'Disease', 'start': 0, 'end': 31, 'mesh': 'D056486'}, {'text': 'Fluvastatin', 'type': 'Chemical', 'start': 54, 'end': 65, 'mesh': 'C065180'}, {'text': 'statins', 'type': 'Chemical', 'start': 84, 'end': 91, 'mesh': 'D019161'}, {'text': 'drug-induced liver injury', 'type': 'Disease', 'start': 144, 'end': 169, 'mesh': 'D056486'}, {'text': 'liver damage', 'type': 'Disease', 'start': 256, 'end': 268, 'mesh': 'D056486'}, {'text': 'fluvastatin', 'type': 'Chemical', 'start': 325, 'end': 336, 'mesh': 'C065180'}, {'text': 'nausea', 'type': 'Disease', 'start': 386, 'end': 392, 'mesh': 'D009325'}, {'text': 'anorexia', 'type': 'Disease', 'start': 394, 'end': 402, 'mesh': 'D000855'}, {'text': 'abdominal pain', 'type': 'Disease', 'start': 414, 'end': 428, 'mesh': 'D015746'}, {'text': 'creatine', 'type': 'Chemical', 'start': 468, 'end': 476, 'mesh': 'D003401'}, {'text': 'fluvastatin', 'type': 'Chemical', 'start': 627, 'end': 638, 'mesh': 'C065180'}, {'text': 'hepatic damage', 'type': 'Disease', 'start': 696, 'end': 710, 'mesh': 'D056486'}]"
+1039,24459006,Fluconazole associated agranulocytosis and thrombocytopenia.,"CASE: We describe a second case of fluconazole associated agranulocytosis with thrombocytopenia and recovery upon discontinuation of therapy. The patient began to have changes in white blood cells and platelets within 48 h of administration of fluconazole and began to recover with 48 h of discontinuation. This case highlights that drug-induced blood dyscrasias can occur unexpectedly as a result of treatment with a commonly used drug thought to be ""safe"". CONCLUSION: According to Naranjo's algorithm the likelihood that our patient's agranulocytosis and thrombocytopenia occurred as a result of therapy with fluconazole is probable, with a total of six points. We feel that the weight of the overall evidence of this evidence is strong. In particular the temporal relationship of bone marrow suppression to the initiation of fluconazole and the abatement of symptoms that rapidly reversed immediately following discontinuation.","[{'text': 'Fluconazole', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D015725'}, {'text': 'agranulocytosis', 'type': 'Disease', 'start': 23, 'end': 38, 'mesh': 'D000380'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 43, 'end': 59, 'mesh': 'D013921'}, {'text': 'fluconazole', 'type': 'Chemical', 'start': 96, 'end': 107, 'mesh': 'D015725'}, {'text': 'agranulocytosis', 'type': 'Disease', 'start': 119, 'end': 134, 'mesh': 'D000380'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 140, 'end': 156, 'mesh': 'D013921'}, {'text': 'fluconazole', 'type': 'Chemical', 'start': 305, 'end': 316, 'mesh': 'D015725'}, {'text': 'blood dyscrasias', 'type': 'Disease', 'start': 407, 'end': 423, 'mesh': 'D006402'}, {'text': 'agranulocytosis', 'type': 'Disease', 'start': 599, 'end': 614, 'mesh': 'D000380'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 619, 'end': 635, 'mesh': 'D013921'}, {'text': 'fluconazole', 'type': 'Chemical', 'start': 673, 'end': 684, 'mesh': 'D015725'}, {'text': 'bone marrow suppression', 'type': 'Disease', 'start': 845, 'end': 868, 'mesh': 'D001855'}, {'text': 'fluconazole', 'type': 'Chemical', 'start': 890, 'end': 901, 'mesh': 'D015725'}]"
+1040,24464946,Two-dimensional speckle tracking echocardiography combined with high-sensitive cardiac troponin T in early detection and prediction of cardiotoxicity during epirubicine-based chemotherapy.,"AIMS: To investigate whether alterations of myocardial strain and high-sensitive cardiac troponin T (cTnT) could predict future cardiac dysfunction in patients after epirubicin exposure. METHODS: Seventy-five patients with non-Hodgkin lymphoma treated with epirubicin were studied. Blood collection and echocardiography were performed at baseline, 1 day after the third cycle, and 1 day after completion of chemotherapy. Patients were studied using echocardiography during follow-up. Global longitudinal (GLS), circumferential (GCS), and radial strain (GRS) were calculated using speckle tracking echocardiography. Left ventricular ejection fraction was analysed by real-time 3D echocardiography. Cardiotoxicity was defined as a reduction of the LVEF of >5% to <55% with symptoms of heart failure or an asymptomatic reduction of the LVEF of >10% to <55%. RESULTS: Fourteen patients (18.67%) developed cardiotoxicity after treatment. GLS (-18.48 + 1.72% vs. -15.96 + 1.6%), GCS (-20.93 + 2.86% vs. -19.20 + 3.21%), and GRS (39.23 + 6.44% vs. 34.98 + 6.2%) were markedly reduced and cTnT was elevated from 0.0010 + 0.0020 to 0.0073 + 0.0038 ng/mL (P all < 0.01) at the completion of chemotherapy compared with baseline values. A >15.9% decrease in GLS [sensitivity, 86%; specificity, 75%; area under the curve (AUC) = 0.815; P = 0.001] and a >0.004 ng/mL elevation in cTnT (sensitivity, 79%; specificity, 64%; AUC = 0.757; P = 0.005) from baseline to the third cycle of chemotherapy predicted later cardiotoxicity. The decrease in GLS remained the only independent predictor of cardiotoxicity (P = 0.000). CONCLUSIONS: GLS combined with cTnT may provide a reliable and non-invasive method to predict cardiac dysfunction in patients receiving anthracycline-based chemotherapy.","[{'text': 'cardiotoxicity', 'type': 'Disease', 'start': 135, 'end': 149, 'mesh': 'D066126'}, {'text': 'epirubicine', 'type': 'Chemical', 'start': 157, 'end': 168, 'mesh': 'D015251'}, {'text': 'myocardial strain', 'type': 'Disease', 'start': 233, 'end': 250, 'mesh': 'D009202'}, {'text': 'cardiac dysfunction', 'type': 'Disease', 'start': 317, 'end': 336, 'mesh': 'D006331'}, {'text': 'epirubicin', 'type': 'Chemical', 'start': 355, 'end': 365, 'mesh': 'D015251'}, {'text': 'non-Hodgkin lymphoma', 'type': 'Disease', 'start': 412, 'end': 432, 'mesh': 'D008228'}, {'text': 'epirubicin', 'type': 'Chemical', 'start': 446, 'end': 456, 'mesh': 'D015251'}, {'text': 'Cardiotoxicity', 'type': 'Disease', 'start': 886, 'end': 900, 'mesh': 'D066126'}, {'text': 'heart failure', 'type': 'Disease', 'start': 972, 'end': 985, 'mesh': 'D006333'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1090, 'end': 1104, 'mesh': 'D066126'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1686, 'end': 1700, 'mesh': 'D066126'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1765, 'end': 1779, 'mesh': 'D066126'}, {'text': 'cardiac dysfunction', 'type': 'Disease', 'start': 1887, 'end': 1906, 'mesh': 'D006331'}, {'text': 'anthracycline', 'type': 'Chemical', 'start': 1929, 'end': 1942, 'mesh': 'D018943'}]"
+1041,24535067,"Prevention of etomidate-induced myoclonus: which is superior: Fentanyl, midazolam, or a combination? A Retrospective comparative study.","BACKGROUND: In this retrospective comparative study, we aimed to compare the effectiveness of fentanyl, midazolam, and a combination of fentanyl and midazolam to prevent etomidate-induced myoclonus. MATERIAL AND METHODS: This study was performed based on anesthesia records. Depending on the drugs that would be given before the induction of anesthesia with etomidate, the patients were separated into 4 groups: no pretreatment (Group NP), fentanyl 1 ug.kg-1 (Group F), midazolam 0.03 mg.kg-1 (Group M), and midazolam 0.015 mg.kg-1 + fentanyl 0.5 ug.kg-1 (Group FM). Patients who received the same anesthetic procedure were selected: 2 minutes after intravenous injections of the pretreatment drugs, anesthesia is induced with 0.3 mg.kg-1 etomidate injected intravenously over a period of 20-30 seconds. Myoclonic movements are evaluated, which were observed and graded according to clinical severity during the 2 minutes after etomidate injection. The severity of pain due to etomidate injection, mean arterial pressure, heart rate, and adverse effects were also evaluated. RESULTS: Study results showed that myoclonus incidence was 85%, 40%, 70%, and 25% in Group NP, Group F, Group M, and Group FM, respectively, and were significantly lower in Group F and Group FM. CONCLUSIONS: We conclude that pretreatment with fentanyl or combination of fentanyl and midazolam was effective in preventing etomidate-induced myoclonus.","[{'text': 'etomidate', 'type': 'Chemical', 'start': 14, 'end': 23, 'mesh': 'D005045'}, {'text': 'myoclonus', 'type': 'Disease', 'start': 32, 'end': 41, 'mesh': 'D009207'}, {'text': 'Fentanyl', 'type': 'Chemical', 'start': 62, 'end': 70, 'mesh': 'D005283'}, {'text': 'midazolam', 'type': 'Chemical', 'start': 72, 'end': 81, 'mesh': 'D008874'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 230, 'end': 238, 'mesh': 'D005283'}, {'text': 'midazolam', 'type': 'Chemical', 'start': 240, 'end': 249, 'mesh': 'D008874'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 272, 'end': 280, 'mesh': 'D005283'}, {'text': 'midazolam', 'type': 'Chemical', 'start': 285, 'end': 294, 'mesh': 'D008874'}, {'text': 'etomidate', 'type': 'Chemical', 'start': 306, 'end': 315, 'mesh': 'D005045'}, {'text': 'myoclonus', 'type': 'Disease', 'start': 324, 'end': 333, 'mesh': 'D009207'}, {'text': 'etomidate', 'type': 'Chemical', 'start': 494, 'end': 503, 'mesh': 'D005045'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 576, 'end': 584, 'mesh': 'D005283'}, {'text': 'midazolam', 'type': 'Chemical', 'start': 606, 'end': 615, 'mesh': 'D008874'}, {'text': 'midazolam', 'type': 'Chemical', 'start': 644, 'end': 653, 'mesh': 'D008874'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 670, 'end': 678, 'mesh': 'D005283'}, {'text': 'etomidate', 'type': 'Chemical', 'start': 875, 'end': 884, 'mesh': 'D005045'}, {'text': 'Myoclonic movements', 'type': 'Disease', 'start': 940, 'end': 959, 'mesh': 'D009069'}, {'text': 'etomidate', 'type': 'Chemical', 'start': 1064, 'end': 1073, 'mesh': 'D005045'}, {'text': 'pain', 'type': 'Disease', 'start': 1101, 'end': 1105, 'mesh': 'D010146'}, {'text': 'etomidate', 'type': 'Chemical', 'start': 1113, 'end': 1122, 'mesh': 'D005045'}, {'text': 'myoclonus', 'type': 'Disease', 'start': 1246, 'end': 1255, 'mesh': 'D009207'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 1454, 'end': 1462, 'mesh': 'D005283'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 1481, 'end': 1489, 'mesh': 'D005283'}, {'text': 'midazolam', 'type': 'Chemical', 'start': 1494, 'end': 1503, 'mesh': 'D008874'}, {'text': 'etomidate', 'type': 'Chemical', 'start': 1532, 'end': 1541, 'mesh': 'D005045'}, {'text': 'myoclonus', 'type': 'Disease', 'start': 1550, 'end': 1559, 'mesh': 'D009207'}]"
+1042,24554916,Cholestatic presentation of yellow phosphorus poisoning.,"Yellow phosphorus, a component of certain pesticide pastes and fireworks, is well known to cause hepatotoxicity. Poisoning with yellow phosphorus classically manifests with acute hepatitis leading to acute liver failure which may need liver transplantation. We present a case of yellow phosphorus poisoning in which a patient presented with florid clinical features of cholestasis highlighting the fact that cholestasis can rarely be a presenting feature of yellow phosphorus hepatotoxicity.","[{'text': 'Cholestatic', 'type': 'Disease', 'start': 0, 'end': 11, 'mesh': 'D002779'}, {'text': 'phosphorus', 'type': 'Chemical', 'start': 35, 'end': 45, 'mesh': 'D010758'}, {'text': 'poisoning', 'type': 'Disease', 'start': 46, 'end': 55, 'mesh': 'D011041'}, {'text': 'phosphorus', 'type': 'Chemical', 'start': 64, 'end': 74, 'mesh': 'D010758'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 154, 'end': 168, 'mesh': 'D056486'}, {'text': 'Poisoning', 'type': 'Disease', 'start': 170, 'end': 179, 'mesh': 'D011041'}, {'text': 'phosphorus', 'type': 'Chemical', 'start': 192, 'end': 202, 'mesh': 'D010758'}, {'text': 'acute hepatitis', 'type': 'Disease', 'start': 230, 'end': 245, 'mesh': 'D006505'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 257, 'end': 276, 'mesh': 'D017114'}, {'text': 'phosphorus', 'type': 'Chemical', 'start': 343, 'end': 353, 'mesh': 'D010758'}, {'text': 'poisoning', 'type': 'Disease', 'start': 354, 'end': 363, 'mesh': 'D011041'}, {'text': 'cholestasis', 'type': 'Disease', 'start': 426, 'end': 437, 'mesh': 'D002779'}, {'text': 'cholestasis', 'type': 'Disease', 'start': 465, 'end': 476, 'mesh': 'D002779'}, {'text': 'phosphorus', 'type': 'Chemical', 'start': 522, 'end': 532, 'mesh': 'D010758'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 533, 'end': 547, 'mesh': 'D056486'}]"
+1043,24571687,Vasovagal syncope and severe bradycardia following intranasal dexmedetomidine for pediatric procedural sedation.,"We report syncope and bradycardia in an 11-year-old girl following administration of intranasal dexmedetomidine for sedation for a voiding cystourethrogram. Following successful completion of VCUG and a 60-min recovery period, the patient's level of consciousness and vital signs returned to presedation levels. Upon leaving the sedation area, the patient collapsed, with no apparent inciting event. The patient quickly regained consciousness and no injury occurred. The primary abnormality found was persistent bradycardia, and she was admitted to the hospital for telemetric observation. The bradycardia lasted ~2 h, and further cardiac workup revealed no underlying abnormality. Unanticipated and previously unreported outcomes may be witnessed as we expand the use of certain sedatives to alternative routes of administration.","[{'text': 'Vasovagal syncope', 'type': 'Disease', 'start': 0, 'end': 17, 'mesh': 'D019462'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 29, 'end': 40, 'mesh': 'D001919'}, {'text': 'dexmedetomidine', 'type': 'Chemical', 'start': 62, 'end': 77, 'mesh': 'D020927'}, {'text': 'syncope', 'type': 'Disease', 'start': 123, 'end': 130, 'mesh': 'D013575'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 135, 'end': 146, 'mesh': 'D001919'}, {'text': 'dexmedetomidine', 'type': 'Chemical', 'start': 209, 'end': 224, 'mesh': 'D020927'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 625, 'end': 636, 'mesh': 'D001919'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 707, 'end': 718, 'mesh': 'D001919'}]"
+1044,24582773,Paradoxical severe agitation induced by add-on high-doses quetiapine in schizo-affective disorder.,"We report the case of a 35-year-old patient suffering from schizo-affective disorder since the age of 19 years, treated by a combination of first-generation antipsychotics, zuclopenthixol (100 mg/day) and lithium (1200 mg/day) (serum lithium=0.85 mEq/l). This patient had no associated personality disorder (particularly no antisocial disorder) and no substance abuse disorder. Within the 48 h following the gradual introduction of quetiapine (up to 600 mg/day), the patient presented severe agitation without an environmental explanation, contrasting with the absence of a history of aggressiveness or personality disorder. The diagnoses of manic shift and akathisia were dismissed. The withdrawal and the gradual reintroduction of quetiapine 2 weeks later, which led to another severe agitation, enabled us to attribute the agitation specifically to quetiapine.","[{'text': 'agitation', 'type': 'Disease', 'start': 19, 'end': 28, 'mesh': 'D011595'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 58, 'end': 68, 'mesh': 'C069541'}, {'text': 'schizo-affective disorder', 'type': 'Disease', 'start': 72, 'end': 97, 'mesh': 'D011618'}, {'text': 'schizo-affective disorder', 'type': 'Disease', 'start': 158, 'end': 183, 'mesh': 'D011618'}, {'text': 'zuclopenthixol', 'type': 'Chemical', 'start': 272, 'end': 286, 'mesh': 'D003006'}, {'text': 'lithium', 'type': 'Chemical', 'start': 304, 'end': 311, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 333, 'end': 340, 'mesh': 'D008094'}, {'text': 'personality disorder', 'type': 'Disease', 'start': 385, 'end': 405, 'mesh': 'D010554'}, {'text': 'antisocial disorder', 'type': 'Disease', 'start': 423, 'end': 442, 'mesh': 'D000987'}, {'text': 'substance abuse disorder', 'type': 'Disease', 'start': 451, 'end': 475, 'mesh': 'D019966'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 531, 'end': 541, 'mesh': 'C069541'}, {'text': 'agitation', 'type': 'Disease', 'start': 591, 'end': 600, 'mesh': 'D011595'}, {'text': 'aggressiveness', 'type': 'Disease', 'start': 684, 'end': 698, 'mesh': 'D010554'}, {'text': 'personality disorder', 'type': 'Disease', 'start': 702, 'end': 722, 'mesh': 'D010554'}, {'text': 'manic', 'type': 'Disease', 'start': 741, 'end': 746, 'mesh': 'D001714'}, {'text': 'akathisia', 'type': 'Disease', 'start': 757, 'end': 766, 'mesh': 'D017109'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 832, 'end': 842, 'mesh': 'C069541'}, {'text': 'agitation', 'type': 'Disease', 'start': 886, 'end': 895, 'mesh': 'D011595'}, {'text': 'agitation', 'type': 'Disease', 'start': 925, 'end': 934, 'mesh': 'D011595'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 951, 'end': 961, 'mesh': 'C069541'}]"
+1045,24587916,Antioxidant effects of bovine lactoferrin on dexamethasone-induced hypertension in rat.,"Dexamethasone- (Dex-) induced hypertension is associated with enhanced oxidative stress. Lactoferrin (LF) is an iron-binding glycoprotein with antihypertensive properties. In this study, we investigated the effect of chronic administration of LF on oxidative stress and hypertension upon Dex administration. Male Wistar rats were treated by Dex (30  u g/kg/day subcutaneously) or saline for 14 days. Oral bovine LF (30, 100, 300 mg/kg) was given from day 8 to 14 in a reversal study. In a prevention study, rats received 4 days of LF treatment followed by Dex and continued during the test period. Systolic blood pressure (SBP) was measured using tail-cuff method. Thymus weight was used as a marker of glucocorticoid activity. Plasma hydrogen peroxide (H2O2) concentration and ferric reducing antioxidant power (FRAP) value were determined. Dexamethasone significantly increased SBP and plasma H2O2 level and decreased thymus and body weights. LF lowered (P < 0.01) and dose dependently prevented (P < 0.001) Dex-induced hypertension. LF prevented body weight loss and significantly reduced the elevated plasma H2O2 and increased FRAP values. Chronic administration of LF strongly reduced the blood pressure and production of ROS and improved antioxidant capacity in Dex-induced hypertension, suggesting the role of inhibition of oxidative stress as another mechanism of antihypertensive action of LF.","[{'text': 'dexamethasone', 'type': 'Chemical', 'start': 45, 'end': 58, 'mesh': 'D003907'}, {'text': 'hypertension', 'type': 'Disease', 'start': 67, 'end': 79, 'mesh': 'D006973'}, {'text': 'Dexamethasone', 'type': 'Chemical', 'start': 88, 'end': 101, 'mesh': 'D003907'}, {'text': 'Dex', 'type': 'Chemical', 'start': 104, 'end': 107, 'mesh': 'D003907'}, {'text': 'hypertension', 'type': 'Disease', 'start': 118, 'end': 130, 'mesh': 'D006973'}, {'text': 'iron', 'type': 'Chemical', 'start': 200, 'end': 204, 'mesh': 'D007501'}, {'text': 'hypertension', 'type': 'Disease', 'start': 358, 'end': 370, 'mesh': 'D006973'}, {'text': 'Dex', 'type': 'Chemical', 'start': 376, 'end': 379, 'mesh': 'D003907'}, {'text': 'Dex', 'type': 'Chemical', 'start': 429, 'end': 432, 'mesh': 'D003907'}, {'text': 'Dex', 'type': 'Chemical', 'start': 644, 'end': 647, 'mesh': 'D003907'}, {'text': 'hydrogen peroxide', 'type': 'Chemical', 'start': 823, 'end': 840, 'mesh': 'D006861'}, {'text': 'H2O2', 'type': 'Chemical', 'start': 842, 'end': 846, 'mesh': 'D006861'}, {'text': 'Dexamethasone', 'type': 'Chemical', 'start': 930, 'end': 943, 'mesh': 'D003907'}, {'text': 'H2O2', 'type': 'Chemical', 'start': 983, 'end': 987, 'mesh': 'D006861'}, {'text': 'Dex', 'type': 'Chemical', 'start': 1098, 'end': 1101, 'mesh': 'D003907'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1110, 'end': 1122, 'mesh': 'D006973'}, {'text': 'weight loss', 'type': 'Disease', 'start': 1142, 'end': 1153, 'mesh': 'D015431'}, {'text': 'H2O2', 'type': 'Chemical', 'start': 1200, 'end': 1204, 'mesh': 'D006861'}, {'text': 'Dex', 'type': 'Chemical', 'start': 1356, 'end': 1359, 'mesh': 'D003907'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1368, 'end': 1380, 'mesh': 'D006973'}]"
+1046,24588023,The association between tranexamic acid and convulsive seizures after cardiac surgery: a multivariate analysis in 11 529 patients.,"Because of a lack of contemporary data regarding seizures after cardiac surgery, we undertook a retrospective analysis of prospectively collected data from 11 529 patients in whom cardiopulmonary bypass was used from January 2004 to December 2010. A convulsive seizure was defined as a transient episode of disturbed brain function characterised by abnormal involuntary motor movements. Multivariate regression analysis was performed to identify independent predictors of postoperative seizures. A total of 100 (0.9%) patients developed postoperative convulsive seizures. Generalised and focal seizures were identified in 68 and 32 patients, respectively. The median (IQR [range]) time after surgery when the seizure occurred was 7 (6-12 [1-216]) h and 8 (6-11 [4-18]) h, respectively. Epileptiform findings on electroencephalography were seen in 19 patients. Independent predictors of postoperative seizures included age, female sex, redo cardiac surgery, calcification of ascending aorta, congestive heart failure, deep hypothermic circulatory arrest, duration of aortic cross-clamp and tranexamic acid. When tested in a multivariate regression analysis, tranexamic acid was a strong independent predictor of seizures (OR 14.3, 95% CI 5.5-36.7; p < 0.001). Patients with convulsive seizures had 2.5 times higher in-hospital mortality rates and twice the length of hospital stay compared with patients without convulsive seizures. Mean (IQR [range]) length of stay in the intensive care unit was 115 (49-228 [32-481]) h in patients with convulsive seizures compared with 26 (22-69 [14-1080]) h in patients without seizures (p < 0.001). Convulsive seizures are a serious postoperative complication after cardiac surgery. As tranexamic acid is the only modifiable factor, its administration, particularly in doses exceeding 80 mg.kg(-1), should be weighed against the risk of postoperative seizures.","[{'text': 'tranexamic acid', 'type': 'Chemical', 'start': 24, 'end': 39, 'mesh': 'D014148'}, {'text': 'convulsive', 'type': 'Disease', 'start': 44, 'end': 54, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 55, 'end': 63, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 180, 'end': 188, 'mesh': 'D012640'}, {'text': 'convulsive', 'type': 'Disease', 'start': 381, 'end': 391, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 392, 'end': 399, 'mesh': 'D012640'}, {'text': 'abnormal involuntary motor movements', 'type': 'Disease', 'start': 480, 'end': 516, 'mesh': 'D004409'}, {'text': 'seizures', 'type': 'Disease', 'start': 617, 'end': 625, 'mesh': 'D012640'}, {'text': 'convulsive', 'type': 'Disease', 'start': 682, 'end': 692, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 693, 'end': 701, 'mesh': 'D012640'}, {'text': 'Generalised and focal seizures', 'type': 'Disease', 'start': 703, 'end': 733, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 840, 'end': 847, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 1031, 'end': 1039, 'mesh': 'D012640'}, {'text': 'congestive heart failure', 'type': 'Disease', 'start': 1122, 'end': 1146, 'mesh': 'D006333'}, {'text': 'hypothermic', 'type': 'Disease', 'start': 1153, 'end': 1164, 'mesh': 'D007035'}, {'text': 'tranexamic acid', 'type': 'Chemical', 'start': 1220, 'end': 1235, 'mesh': 'D014148'}, {'text': 'tranexamic acid', 'type': 'Chemical', 'start': 1288, 'end': 1303, 'mesh': 'D014148'}, {'text': 'seizures', 'type': 'Disease', 'start': 1342, 'end': 1350, 'mesh': 'D012640'}, {'text': 'convulsive', 'type': 'Disease', 'start': 1404, 'end': 1414, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 1415, 'end': 1423, 'mesh': 'D012640'}, {'text': 'convulsive', 'type': 'Disease', 'start': 1542, 'end': 1552, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 1553, 'end': 1561, 'mesh': 'D012640'}, {'text': 'convulsive', 'type': 'Disease', 'start': 1669, 'end': 1679, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 1680, 'end': 1688, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 1746, 'end': 1754, 'mesh': 'D012640'}, {'text': 'Convulsive', 'type': 'Disease', 'start': 1768, 'end': 1778, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 1779, 'end': 1787, 'mesh': 'D012640'}, {'text': 'postoperative complication', 'type': 'Disease', 'start': 1802, 'end': 1828, 'mesh': 'D011183'}, {'text': 'tranexamic acid', 'type': 'Chemical', 'start': 1855, 'end': 1870, 'mesh': 'D014148'}, {'text': 'seizures', 'type': 'Disease', 'start': 2020, 'end': 2028, 'mesh': 'D012640'}]"
+1047,24595967,Dysfunctional overnight memory consolidation in ecstasy users.,"Sleep plays an important role in the consolidation and integration of memory in a process called overnight memory consolidation. Previous studies indicate that ecstasy users have marked and persistent neurocognitive and sleep-related impairments. We extend past research by examining overnight memory consolidation among regular ecstasy users (n=12) and drug naive healthy controls (n=26). Memory recall of word pairs was evaluated before and after a period of sleep, with and without interference prior to testing. In addition, we assessed neurocognitive performances across tasks of learning, memory and executive functioning. Ecstasy users demonstrated impaired overnight memory consolidation, a finding that was more pronounced following associative interference. Additionally, ecstasy users demonstrated impairments on tasks recruiting frontostriatal and hippocampal neural circuitry, in the domains of proactive interference memory, long-term memory, encoding, working memory and complex planning. We suggest that ecstasy-associated dysfunction in fronto-temporal circuitry may underlie overnight consolidation memory impairments in regular ecstasy users.","[{'text': 'Dysfunctional overnight memory', 'type': 'Disease', 'start': 0, 'end': 30, 'mesh': 'D008569'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 48, 'end': 55, 'mesh': 'D018817'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 223, 'end': 230, 'mesh': 'D018817'}, {'text': 'sleep-related impairments', 'type': 'Disease', 'start': 283, 'end': 308, 'mesh': 'D012893'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 392, 'end': 399, 'mesh': 'D018817'}, {'text': 'Ecstasy', 'type': 'Chemical', 'start': 692, 'end': 699, 'mesh': 'D018817'}, {'text': 'impaired overnight memory', 'type': 'Disease', 'start': 719, 'end': 744, 'mesh': 'D008569'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 845, 'end': 852, 'mesh': 'D018817'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 1083, 'end': 1090, 'mesh': 'D018817'}, {'text': 'memory impairments', 'type': 'Disease', 'start': 1180, 'end': 1198, 'mesh': 'D008569'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 1210, 'end': 1217, 'mesh': 'D018817'}]"
+1048,24614773,Normoammonemic encephalopathy: solely valproate induced or multiple mechanisms?,"A 77-year-old woman presented with subacute onset progressive confusion, aggression, auditory hallucinations and delusions. In the preceding months, the patient had a number of admissions with transient unilateral hemiparesis with facial droop, and had been started on valproate for presumed hemiplegic migraine. Valproate was withdrawn soon after admission and her cognitive abilities have gradually improved over 3 months of follow-up. Valproate levels taken prior to withdrawal were subtherapeutic and the patient was normoammonaemic. EEG undertaken during inpatient stay showed changes consistent with encephalopathy, and low titre N-methyl-D-aspartate (NMDA) receptor antibodies were present in this patient. The possible aetiologies of valproate-induced encephalopathy and NMDA receptor-associated encephalitis present a diagnostic dilemma. We present a putative combinatorial hypothesis to explain this patient's symptoms.","[{'text': 'encephalopathy', 'type': 'Disease', 'start': 15, 'end': 29, 'mesh': 'D001927'}, {'text': 'valproate', 'type': 'Chemical', 'start': 38, 'end': 47, 'mesh': 'D014635'}, {'text': 'confusion', 'type': 'Disease', 'start': 142, 'end': 151, 'mesh': 'D003221'}, {'text': 'aggression', 'type': 'Disease', 'start': 153, 'end': 163, 'mesh': 'D001523'}, {'text': 'auditory hallucinations', 'type': 'Disease', 'start': 165, 'end': 188, 'mesh': 'D006212'}, {'text': 'delusions', 'type': 'Disease', 'start': 193, 'end': 202, 'mesh': 'D003072'}, {'text': 'hemiparesis', 'type': 'Disease', 'start': 294, 'end': 305, 'mesh': 'D010291'}, {'text': 'valproate', 'type': 'Chemical', 'start': 349, 'end': 358, 'mesh': 'D014635'}, {'text': 'hemiplegic migraine', 'type': 'Disease', 'start': 372, 'end': 391, 'mesh': 'D020325'}, {'text': 'Valproate', 'type': 'Chemical', 'start': 393, 'end': 402, 'mesh': 'D014635'}, {'text': 'Valproate', 'type': 'Chemical', 'start': 518, 'end': 527, 'mesh': 'D014635'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 686, 'end': 700, 'mesh': 'D001927'}, {'text': 'N-methyl-D-aspartate', 'type': 'Chemical', 'start': 716, 'end': 736, 'mesh': 'D016202'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 738, 'end': 742, 'mesh': 'D016202'}, {'text': 'valproate', 'type': 'Chemical', 'start': 822, 'end': 831, 'mesh': 'D014635'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 840, 'end': 854, 'mesh': 'D001927'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 859, 'end': 863, 'mesh': 'D016202'}, {'text': 'encephalitis', 'type': 'Disease', 'start': 884, 'end': 896, 'mesh': 'D004660'}]"
+1049,24618873,Cerebellar and oculomotor dysfunction induced by rapid infusion of pethidine.,"Pethidine is an opioid that gains its popularity for the effective pain control through acting on the opioid-receptors. However, rapid pain relief sometimes brings about unfavourable side effects that largely limit its clinical utility. Common side effects include nausea, vomiting and hypotension. In patients with impaired renal and liver function, and those who need long-term pain control, pethidine may cause excitatory central nervous system (CNS) effects through its neurotoxic metabolite, norpethidine, resulting in irritability and seizure attack. On the contrary, though not clinically apparent, pethidine potentially causes inhibitory impacts on the CNS and impairs normal cerebellar and oculomotor function in the short term. In this case report, we highlight opioid's inhibitory side effects on the cerebellar structure that causes dysmetria, dysarthria, reduced smooth pursuit gain and decreased saccadic velocity.","[{'text': 'pethidine', 'type': 'Chemical', 'start': 67, 'end': 76, 'mesh': 'D008614'}, {'text': 'Pethidine', 'type': 'Chemical', 'start': 78, 'end': 87, 'mesh': 'D008614'}, {'text': 'pain', 'type': 'Disease', 'start': 145, 'end': 149, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 213, 'end': 217, 'mesh': 'D010146'}, {'text': 'nausea', 'type': 'Disease', 'start': 343, 'end': 349, 'mesh': 'D009325'}, {'text': 'vomiting', 'type': 'Disease', 'start': 351, 'end': 359, 'mesh': 'D014839'}, {'text': 'hypotension', 'type': 'Disease', 'start': 364, 'end': 375, 'mesh': 'D007022'}, {'text': 'pain', 'type': 'Disease', 'start': 458, 'end': 462, 'mesh': 'D010146'}, {'text': 'pethidine', 'type': 'Chemical', 'start': 472, 'end': 481, 'mesh': 'D008614'}, {'text': 'neurotoxic', 'type': 'Disease', 'start': 552, 'end': 562, 'mesh': 'D020258'}, {'text': 'norpethidine', 'type': 'Chemical', 'start': 575, 'end': 587, 'mesh': 'C002752'}, {'text': 'irritability', 'type': 'Disease', 'start': 602, 'end': 614, 'mesh': 'D001523'}, {'text': 'seizure', 'type': 'Disease', 'start': 619, 'end': 626, 'mesh': 'D012640'}, {'text': 'pethidine', 'type': 'Chemical', 'start': 684, 'end': 693, 'mesh': 'D008614'}, {'text': 'dysmetria', 'type': 'Disease', 'start': 923, 'end': 932, 'mesh': 'D002524'}, {'text': 'dysarthria', 'type': 'Disease', 'start': 934, 'end': 944, 'mesh': 'D004401'}]"
+1050,24641119,Baboon syndrome induced by ketoconazole.,"A 27-year-old male patient presented with a maculopapular eruption on the flexural areas and buttocks after using oral ketoconazole. The patient was diagnosed with drug-induced baboon syndrome based on his history, which included prior sensitivity to topical ketoconazole, a physical examination, and histopathological findings. Baboon syndrome is a drug- or contact allergen-related maculopapular eruption that typically involves the flexural and gluteal areas. To the best of our knowledge, this is the first reported case of ketoconazole-induced baboon syndrome in the English literature.","[{'text': 'Baboon syndrome', 'type': 'Disease', 'start': 0, 'end': 15, 'mesh': '-1'}, {'text': 'ketoconazole', 'type': 'Chemical', 'start': 27, 'end': 39, 'mesh': 'D007654'}, {'text': 'maculopapular eruption', 'type': 'Disease', 'start': 85, 'end': 107, 'mesh': 'D003875'}, {'text': 'ketoconazole', 'type': 'Chemical', 'start': 160, 'end': 172, 'mesh': 'D007654'}, {'text': 'baboon syndrome', 'type': 'Disease', 'start': 218, 'end': 233, 'mesh': '-1'}, {'text': 'ketoconazole', 'type': 'Chemical', 'start': 300, 'end': 312, 'mesh': 'D007654'}, {'text': 'Baboon syndrome', 'type': 'Disease', 'start': 370, 'end': 385, 'mesh': '-1'}, {'text': 'maculopapular eruption', 'type': 'Disease', 'start': 425, 'end': 447, 'mesh': 'D003875'}, {'text': 'ketoconazole', 'type': 'Chemical', 'start': 569, 'end': 581, 'mesh': 'D007654'}, {'text': 'baboon syndrome', 'type': 'Disease', 'start': 590, 'end': 605, 'mesh': '-1'}]"
+1051,24653743,A Case of Sudden Cardiac Death due to Pilsicainide-Induced Torsades de Pointes.,"An 84-year-old male received oral pilsicainide, a pure sodium channel blocker with slow recovery kinetics, to convert his paroxysmal atrial fibrillation to a sinus rhythm; the patient developed sudden cardiac death two days later. The Holter electrocardiogram, which was worn by chance, revealed torsade de pointes with gradually prolonged QT intervals. This drug is rapidly absorbed from the gastrointestinal tract, and most of it is excreted from the kidney. Although the patient's renal function was not highly impaired and the dose of pilsicainide was low, the plasma concentration of pilsicainide may have been high, which can produce torsades de pointes in the octogenarian. Although the oral administration of class IC drugs, including pilsicainide, is effective to terminate atrial fibrillation, careful consideration must be taken before giving these drugs to octogenarians.","[{'text': 'Sudden Cardiac Death', 'type': 'Disease', 'start': 10, 'end': 30, 'mesh': 'D016757'}, {'text': 'Pilsicainide', 'type': 'Chemical', 'start': 38, 'end': 50, 'mesh': 'C042288'}, {'text': 'Torsades de Pointes', 'type': 'Disease', 'start': 59, 'end': 78, 'mesh': 'D016171'}, {'text': 'pilsicainide', 'type': 'Chemical', 'start': 114, 'end': 126, 'mesh': 'C042288'}, {'text': 'sodium', 'type': 'Chemical', 'start': 135, 'end': 141, 'mesh': 'D012964'}, {'text': 'atrial fibrillation', 'type': 'Disease', 'start': 213, 'end': 232, 'mesh': 'D001281'}, {'text': 'sudden cardiac death', 'type': 'Disease', 'start': 274, 'end': 294, 'mesh': 'D016757'}, {'text': 'torsade de pointes', 'type': 'Disease', 'start': 376, 'end': 394, 'mesh': 'D016171'}, {'text': 'pilsicainide', 'type': 'Chemical', 'start': 619, 'end': 631, 'mesh': 'C042288'}, {'text': 'pilsicainide', 'type': 'Chemical', 'start': 669, 'end': 681, 'mesh': 'C042288'}, {'text': 'torsades de pointes', 'type': 'Disease', 'start': 720, 'end': 739, 'mesh': 'D016171'}, {'text': 'pilsicainide', 'type': 'Chemical', 'start': 823, 'end': 835, 'mesh': 'C042288'}, {'text': 'atrial fibrillation', 'type': 'Disease', 'start': 863, 'end': 882, 'mesh': 'D001281'}]"
+1052,24658375,All-trans retinoic acid-induced inflammatory myositis in a patient with acute promyelocytic leukemia.,"All-trans retinoic acid (ATRA), a component of standard therapy for acute promyelocytic leukemia (APL), is associated with potentially serious but treatable adverse effects involving numerous organ systems, including rare skeletal muscle involvement. Only a handful of cases of ATRA-induced myositis in children have been reported, and none in the radiology literature. We present such a case in a 15-year-old boy with APL, where recognition of imaging findings played a crucial role in making the diagnosis and facilitated prompt, effective treatment.","[{'text': 'All-trans retinoic acid', 'type': 'Chemical', 'start': 0, 'end': 23, 'mesh': 'D014212'}, {'text': 'myositis', 'type': 'Disease', 'start': 45, 'end': 53, 'mesh': 'D009220'}, {'text': 'acute promyelocytic leukemia', 'type': 'Disease', 'start': 72, 'end': 100, 'mesh': 'D015473'}, {'text': 'All-trans retinoic acid', 'type': 'Chemical', 'start': 102, 'end': 125, 'mesh': 'D014212'}, {'text': 'ATRA', 'type': 'Chemical', 'start': 127, 'end': 131, 'mesh': 'D014212'}, {'text': 'acute promyelocytic leukemia', 'type': 'Disease', 'start': 170, 'end': 198, 'mesh': 'D015473'}, {'text': 'APL', 'type': 'Disease', 'start': 200, 'end': 203, 'mesh': 'D015473'}, {'text': 'ATRA', 'type': 'Chemical', 'start': 380, 'end': 384, 'mesh': 'D014212'}, {'text': 'myositis', 'type': 'Disease', 'start': 393, 'end': 401, 'mesh': 'D009220'}, {'text': 'APL', 'type': 'Disease', 'start': 521, 'end': 524, 'mesh': 'D015473'}]"
+1053,24659727,Tolerability of lomustine in combination with cyclophosphamide in dogs with lymphoma.,"This retrospective study describes toxicity associated with a protocol of lomustine (CCNU) and cyclophosphamide (CTX) in dogs with lymphoma. CCNU was administered per os (PO) at a targeted dosage of 60 mg/m(2) body surface area on day 0, CTX was administered PO at a targeted dosage of 250 mg/m(2) divided over days 0 through 4, and all dogs received prophylactic antibiotics. Ninety treatments were given to the 57 dogs included in the study. Neutropenia was the principal toxic effect, and the overall frequency of grade 4 neutropenia after the first treatment of CCNU/CTX was 30% (95% confidence interval, 19-43%). The mean body weight of dogs with grade 4 neutropenia (19.7 kg + 13.4 kg) was significantly less than the mean body weight of dogs that did not develop grade 4 neutropenia (31.7 kg + 12.4 kg; P = .005). One dog (3%) developed hematologic changes suggestive of hepatotoxicity. No dogs had evidence of either renal toxicity or hemorrhagic cystitis. Adverse gastrointestinal effects were uncommon. On the basis of the findings reported herein, a dose of 60 mg/m(2) of CCNU combined with 250 mg/m(2) of CTX (divided over 5 days) q 4 wk is tolerable in tumor-bearing dogs.","[{'text': 'lomustine', 'type': 'Chemical', 'start': 16, 'end': 25, 'mesh': 'D008130'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 46, 'end': 62, 'mesh': 'D003520'}, {'text': 'lymphoma', 'type': 'Disease', 'start': 76, 'end': 84, 'mesh': 'D008223'}, {'text': 'toxicity', 'type': 'Disease', 'start': 121, 'end': 129, 'mesh': 'D064420'}, {'text': 'lomustine', 'type': 'Chemical', 'start': 160, 'end': 169, 'mesh': 'D008130'}, {'text': 'CCNU', 'type': 'Chemical', 'start': 171, 'end': 175, 'mesh': 'D008130'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 181, 'end': 197, 'mesh': 'D003520'}, {'text': 'CTX', 'type': 'Chemical', 'start': 199, 'end': 202, 'mesh': 'D003520'}, {'text': 'lymphoma', 'type': 'Disease', 'start': 217, 'end': 225, 'mesh': 'D008223'}, {'text': 'CCNU', 'type': 'Chemical', 'start': 227, 'end': 231, 'mesh': 'D008130'}, {'text': 'CTX', 'type': 'Chemical', 'start': 324, 'end': 327, 'mesh': 'D003520'}, {'text': 'Neutropenia', 'type': 'Disease', 'start': 530, 'end': 541, 'mesh': 'D009503'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 611, 'end': 622, 'mesh': 'D009503'}, {'text': 'CCNU', 'type': 'Chemical', 'start': 652, 'end': 656, 'mesh': 'D008130'}, {'text': 'CTX', 'type': 'Chemical', 'start': 657, 'end': 660, 'mesh': 'D003520'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 746, 'end': 757, 'mesh': 'D009503'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 864, 'end': 875, 'mesh': 'D009503'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 964, 'end': 978, 'mesh': 'D056486'}, {'text': 'renal toxicity', 'type': 'Disease', 'start': 1011, 'end': 1025, 'mesh': 'D007674'}, {'text': 'CCNU', 'type': 'Chemical', 'start': 1169, 'end': 1173, 'mesh': 'D008130'}, {'text': 'CTX', 'type': 'Chemical', 'start': 1203, 'end': 1206, 'mesh': 'D003520'}, {'text': 'tumor', 'type': 'Disease', 'start': 1252, 'end': 1257, 'mesh': 'D009369'}]"
+1054,24664478,Nelarabine neurotoxicity with concurrent intrathecal chemotherapy: Case report and review of literature.,"Severe nelarabine neurotoxicity in a patient who received concurrent intrathecal (IT) chemotherapy is reported. A 37-year-old Caucasian woman with a history of T-cell lymphoblastic lymphoma was admitted for relapsed disease. She was originally treated with induction chemotherapy followed by an autologous transplant. She developed relapsed disease 10 months later with leukemic involvement. She was re-induced with nelarabine 1500 mg/m(2) on days 1, 3, and 5 with 1 dose of IT cytarabine 100 mg on day 2 as central nervous system (CNS) prophylaxis. At the time of treatment, she was on continuous renal replacement therapy due to sequelae of tumor lysis syndrome (TLS). She tolerated therapy well, entered a complete remission, and recovered her renal function. She received a second cycle of nelarabine without additional IT prophylaxis one month later. A week after this second cycle, she noted numbness in her lower extremities. Predominantly sensory, though also motor and autonomic, peripheral neuropathy started in her feet, ascended proximally to the mid-thoracic region, and eventually included her distal upper extremities. A magnetic resonance imaging (MRI) of her spine demonstrated changes from C2 to C6 consistent with subacute combined degeneration. Nelarabine was felt to be the cause of her symptoms. Her neuropathy stabilized and showed slight improvement and ultimately received an unrelated, reduced-intensity allogeneic transplant while in complete remission, but relapsed disease 10 weeks later. She is currently being treated with best supportive care. To our knowledge, this is the first published case report of severe neurotoxicity caused by nelarabine in a patient who received concurrent IT chemotherapy.","[{'text': 'Nelarabine', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'C104457'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 11, 'end': 24, 'mesh': 'D020258'}, {'text': 'nelarabine', 'type': 'Chemical', 'start': 112, 'end': 122, 'mesh': 'C104457'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 123, 'end': 136, 'mesh': 'D020258'}, {'text': 'T-cell lymphoblastic lymphoma', 'type': 'Disease', 'start': 265, 'end': 294, 'mesh': 'D054218'}, {'text': 'leukemic', 'type': 'Disease', 'start': 475, 'end': 483, 'mesh': 'D007938'}, {'text': 'nelarabine', 'type': 'Chemical', 'start': 521, 'end': 531, 'mesh': 'C104457'}, {'text': 'cytarabine', 'type': 'Chemical', 'start': 583, 'end': 593, 'mesh': 'D003561'}, {'text': 'tumor lysis syndrome', 'type': 'Disease', 'start': 748, 'end': 768, 'mesh': 'D015275'}, {'text': 'TLS', 'type': 'Disease', 'start': 770, 'end': 773, 'mesh': 'D015275'}, {'text': 'nelarabine', 'type': 'Chemical', 'start': 899, 'end': 909, 'mesh': 'C104457'}, {'text': 'peripheral neuropathy', 'type': 'Disease', 'start': 1094, 'end': 1115, 'mesh': 'D010523'}, {'text': 'Nelarabine', 'type': 'Chemical', 'start': 1370, 'end': 1380, 'mesh': 'C104457'}, {'text': 'neuropathy', 'type': 'Disease', 'start': 1427, 'end': 1437, 'mesh': 'D009422'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 1749, 'end': 1762, 'mesh': 'D020258'}, {'text': 'nelarabine', 'type': 'Chemical', 'start': 1773, 'end': 1783, 'mesh': 'C104457'}]"
+1055,24665854,Valproate-induced hyperammonemic encephalopathy in a renal transplanted patient.,"Neurological complications after renal transplantation constitute an important cause of morbidity and mortality. Their differential diagnosis is difficult and essential for subsequent patient's management. Valproate-induced hyperammonemic encephalopathy is an uncommon but serious effect of valproate treatment. Here, we describe the case of a 15-year-old girl who was on a long-term therapy with valproate due to epilepsy and revealed impaired consciousness with hyperammonemia 12 days after renal transplantation. After withdraw of valproate, patients' symptoms resolved within 24 h. Clinicians should increase their awareness for potential complication of valproate, especially in transplanted patients.","[{'text': 'Valproate', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D014635'}, {'text': 'hyperammonemic', 'type': 'Disease', 'start': 18, 'end': 32, 'mesh': 'D022124'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 33, 'end': 47, 'mesh': 'D001927'}, {'text': 'Neurological complications', 'type': 'Disease', 'start': 81, 'end': 107, 'mesh': 'D009422'}, {'text': 'Valproate', 'type': 'Chemical', 'start': 287, 'end': 296, 'mesh': 'D014635'}, {'text': 'hyperammonemic', 'type': 'Disease', 'start': 305, 'end': 319, 'mesh': 'D022124'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 320, 'end': 334, 'mesh': 'D001927'}, {'text': 'valproate', 'type': 'Chemical', 'start': 372, 'end': 381, 'mesh': 'D014635'}, {'text': 'valproate', 'type': 'Chemical', 'start': 478, 'end': 487, 'mesh': 'D014635'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 495, 'end': 503, 'mesh': 'D004827'}, {'text': 'impaired consciousness', 'type': 'Disease', 'start': 517, 'end': 539, 'mesh': 'D003244'}, {'text': 'hyperammonemia', 'type': 'Disease', 'start': 545, 'end': 559, 'mesh': 'D022124'}, {'text': 'valproate', 'type': 'Chemical', 'start': 615, 'end': 624, 'mesh': 'D014635'}, {'text': 'valproate', 'type': 'Chemical', 'start': 740, 'end': 749, 'mesh': 'D014635'}]"
+1056,24671324,Necrotising fasciitis after bortezomib and dexamethasone-containing regimen in an elderly patient of Waldenstrom macroglobulinaemia.,"Bortezomib and high-dose dexamethasone-containing regimens are considered to be generally tolerable with few severe bacterial infections in patients with B-cell malignancies. However, information is limited concerning the safety of the regimen in elderly patients. We report a case of a 76-year-old man with Waldenstrom macroglobulinaemia who suffered necrotising fasciitis without neutropenia after the combination treatment with bortezomib, high-dose dexamethasone and rituximab. Despite immediate intravenous antimicrobial therapy, he succumbed 23 h after the onset. Physicians should recognise the possibility of fatal bacterial infections related to bortezomib plus high-dose dexamethasone in elderly patients, and we believe this case warrants further investigation.","[{'text': 'Necrotising fasciitis', 'type': 'Disease', 'start': 0, 'end': 21, 'mesh': 'D019115'}, {'text': 'bortezomib', 'type': 'Chemical', 'start': 28, 'end': 38, 'mesh': 'C400082'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 43, 'end': 56, 'mesh': 'D003907'}, {'text': 'Waldenstrom macroglobulinaemia', 'type': 'Disease', 'start': 101, 'end': 131, 'mesh': 'D008258'}, {'text': 'Bortezomib', 'type': 'Chemical', 'start': 133, 'end': 143, 'mesh': 'C400082'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 158, 'end': 171, 'mesh': 'D003907'}, {'text': 'bacterial infections', 'type': 'Disease', 'start': 249, 'end': 269, 'mesh': 'D001424'}, {'text': 'malignancies', 'type': 'Disease', 'start': 294, 'end': 306, 'mesh': 'D009369'}, {'text': 'Waldenstrom macroglobulinaemia', 'type': 'Disease', 'start': 441, 'end': 471, 'mesh': 'D008258'}, {'text': 'necrotising fasciitis', 'type': 'Disease', 'start': 485, 'end': 506, 'mesh': 'D019115'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 515, 'end': 526, 'mesh': 'D009503'}, {'text': 'bortezomib', 'type': 'Chemical', 'start': 564, 'end': 574, 'mesh': 'C400082'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 586, 'end': 599, 'mesh': 'D003907'}, {'text': 'bacterial infections', 'type': 'Disease', 'start': 756, 'end': 776, 'mesh': 'D001424'}, {'text': 'bortezomib', 'type': 'Chemical', 'start': 788, 'end': 798, 'mesh': 'C400082'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 814, 'end': 827, 'mesh': 'D003907'}]"
+1057,24675088,"An integrated characterization of serological, pathological, and functional events in doxorubicin-induced cardiotoxicity.","Many efficacious cancer treatments cause significant cardiac morbidity, yet biomarkers or functional indices of early damage, which would allow monitoring and intervention, are lacking. In this study, we have utilized a rat model of progressive doxorubicin (DOX)-induced cardiomyopathy, applying multiple approaches, including cardiac magnetic resonance imaging (MRI), to provide the most comprehensive characterization to date of the timecourse of serological, pathological, and functional events underlying this toxicity. Hannover Wistar rats were dosed with 1.25 mg/kg DOX weekly for 8 weeks followed by a 4 week off-dosing ""recovery"" period. Electron microscopy of the myocardium revealed subcellular degeneration and marked mitochondrial changes after a single dose. Histopathological analysis revealed progressive cardiomyocyte degeneration, hypertrophy/cytomegaly, and extensive vacuolation after two doses. Extensive replacement fibrosis (quantified by Sirius red staining) developed during the off-dosing period. Functional indices assessed by cardiac MRI (including left ventricular ejection fraction (LVEF), cardiac output, and E/A ratio) declined progressively, reaching statistical significance after two doses and culminating in ""clinical"" LV dysfunction by 12 weeks. Significant increases in peak myocardial contrast enhancement and serological cardiac troponin I (cTnI) emerged after eight doses, importantly preceding the LVEF decline to <50%. Troponin I levels positively correlated with delayed and peak gadolinium contrast enhancement, histopathological grading, and diastolic dysfunction. In summary, subcellular cardiomyocyte degeneration was the earliest marker, followed by progressive functional decline and histopathological manifestations. Myocardial contrast enhancement and elevations in cTnI occurred later. However, all indices predated ""clinical"" LV dysfunction and thus warrant further evaluation as predictive biomarkers.","[{'text': 'doxorubicin', 'type': 'Chemical', 'start': 86, 'end': 97, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 106, 'end': 120, 'mesh': 'D066126'}, {'text': 'cancer', 'type': 'Disease', 'start': 139, 'end': 145, 'mesh': 'D009369'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 367, 'end': 378, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 380, 'end': 383, 'mesh': 'D004317'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 393, 'end': 407, 'mesh': 'D009202'}, {'text': 'toxicity', 'type': 'Disease', 'start': 636, 'end': 644, 'mesh': 'D064420'}, {'text': 'DOX', 'type': 'Chemical', 'start': 694, 'end': 697, 'mesh': 'D004317'}, {'text': 'subcellular degeneration', 'type': 'Disease', 'start': 815, 'end': 839, 'mesh': 'D009410'}, {'text': 'cardiomyocyte degeneration', 'type': 'Disease', 'start': 942, 'end': 968, 'mesh': 'D009410'}, {'text': 'hypertrophy', 'type': 'Disease', 'start': 970, 'end': 981, 'mesh': 'D006984'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 1059, 'end': 1067, 'mesh': 'D005355'}, {'text': 'LV dysfunction', 'type': 'Disease', 'start': 1376, 'end': 1390, 'mesh': 'D018487'}, {'text': 'gadolinium', 'type': 'Chemical', 'start': 1645, 'end': 1655, 'mesh': 'D005682'}, {'text': 'diastolic dysfunction', 'type': 'Disease', 'start': 1709, 'end': 1730, 'mesh': 'D018754'}, {'text': 'cardiomyocyte degeneration', 'type': 'Disease', 'start': 1756, 'end': 1782, 'mesh': 'D009410'}, {'text': 'LV dysfunction', 'type': 'Disease', 'start': 2001, 'end': 2015, 'mesh': 'D018487'}]"
+1058,24684312,Intradermal glutamate and capsaicin injections: intra- and interindividual variability of provoked hyperalgesia and allodynia.,"Intradermal injections of glutamate and capsaicin are attractive to use in human experimental pain models because hyperalgesia and allodynia mimic isolated aspects of clinical pain disorders. The aim of the present study was to investigate the reproducibility of these models. Twenty healthy male volunteers (mean age 24 years; range 18-38 years) received intradermal injections of glutamate and capsaicin in the volar forearm. Magnitudes of secondary pinprick hyperalgesia and brush-evoked allodynia were investigated using von Frey filaments (gauges 10, 15, 60 and 100 g) and brush strokes. Areas of secondary hyperalgesia and allodynia were quantified immediately after injection and after 15, 30 and 60 min. Two identical experiments separated by at least 7 days were performed. Reproducibility across and within volunteers (inter- and intra-individual variation, respectively) was assessed using intraclass correlation coefficient (ICC) and coefficient of variation (CV). Secondary pinprick hyperalgesia was observed as a marked increase in the visual analogue scale (VAS) response to von Frey gauges 60 and 100 g (P < 0.001) after glutamate injection. For capsaicin, secondary pinprick hyperalgesia was detected with all von Frey gauges (P < 0.001). Glutamate evoked reproducible VAS response to all von Frey gauges (ICC > 0.60) and brush strokes (ICC > 0.83). Capsaicin injection was reproducible for secondary hyperalgesia (ICC > 0.70) and allodynia (ICC > 0.71). Intra-individual variability was generally lower for the VAS response to von Frey and brush compared with areas of secondary hyperalgesia and allodynia. In conclusion, glutamate and capsaicin yield reproducible hyperalgesic and allodynic responses, and the present model is well suited for basic research, as well as for assessing the modulation of central phenomena.","[{'text': 'glutamate', 'type': 'Chemical', 'start': 12, 'end': 21, 'mesh': 'D018698'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 26, 'end': 35, 'mesh': 'D002211'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 99, 'end': 111, 'mesh': 'D006930'}, {'text': 'allodynia', 'type': 'Disease', 'start': 116, 'end': 125, 'mesh': 'D006930'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 153, 'end': 162, 'mesh': 'D018698'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 167, 'end': 176, 'mesh': 'D002211'}, {'text': 'pain', 'type': 'Disease', 'start': 221, 'end': 225, 'mesh': 'D010146'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 241, 'end': 253, 'mesh': 'D006930'}, {'text': 'allodynia', 'type': 'Disease', 'start': 258, 'end': 267, 'mesh': 'D006930'}, {'text': 'pain disorders', 'type': 'Disease', 'start': 303, 'end': 317, 'mesh': 'D013001'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 509, 'end': 518, 'mesh': 'D018698'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 523, 'end': 532, 'mesh': 'D002211'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 588, 'end': 600, 'mesh': 'D006930'}, {'text': 'allodynia', 'type': 'Disease', 'start': 618, 'end': 627, 'mesh': 'D006930'}, {'text': 'secondary hyperalgesia', 'type': 'Disease', 'start': 729, 'end': 751, 'mesh': 'D006930'}, {'text': 'allodynia', 'type': 'Disease', 'start': 756, 'end': 765, 'mesh': 'D006930'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 1123, 'end': 1135, 'mesh': 'D006930'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 1264, 'end': 1273, 'mesh': 'D018698'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 1289, 'end': 1298, 'mesh': 'D002211'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 1319, 'end': 1331, 'mesh': 'D006930'}, {'text': 'Glutamate', 'type': 'Chemical', 'start': 1383, 'end': 1392, 'mesh': 'D018698'}, {'text': 'Capsaicin', 'type': 'Chemical', 'start': 1494, 'end': 1503, 'mesh': 'D002211'}, {'text': 'secondary hyperalgesia', 'type': 'Disease', 'start': 1535, 'end': 1557, 'mesh': 'D006930'}, {'text': 'allodynia', 'type': 'Disease', 'start': 1575, 'end': 1584, 'mesh': 'D006930'}, {'text': 'secondary hyperalgesia', 'type': 'Disease', 'start': 1714, 'end': 1736, 'mesh': 'D006930'}, {'text': 'allodynia', 'type': 'Disease', 'start': 1741, 'end': 1750, 'mesh': 'D006930'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 1767, 'end': 1776, 'mesh': 'D018698'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 1781, 'end': 1790, 'mesh': 'D002211'}, {'text': 'hyperalgesic', 'type': 'Disease', 'start': 1810, 'end': 1822, 'mesh': 'D006930'}, {'text': 'allodynic', 'type': 'Disease', 'start': 1827, 'end': 1836, 'mesh': 'D006930'}]"
+1059,24691439,Ocular-specific ER stress reduction rescues glaucoma in murine glucocorticoid-induced glaucoma.,"Administration of glucocorticoids induces ocular hypertension in some patients. If untreated, these patients can develop a secondary glaucoma that resembles primary open-angle glaucoma (POAG). The underlying pathology of glucocorticoid-induced glaucoma is not fully understood, due in part to lack of an appropriate animal model. Here, we developed a murine model of glucocorticoid-induced glaucoma that exhibits glaucoma features that are observed in patients. Treatment of WT mice with topical ocular 0.1% dexamethasone led to elevation of intraocular pressure (IOP), functional and structural loss of retinal ganglion cells, and axonal degeneration, resembling glucocorticoid-induced glaucoma in human patients. Furthermore, dexamethasone-induced ocular hypertension was associated with chronic ER stress of the trabecular meshwork (TM). Similar to patients, withdrawal of dexamethasone treatment reduced elevated IOP and ER stress in this animal model. Dexamethasone induced the transcriptional factor CHOP, a marker for chronic ER stress, in the anterior segment tissues, and Chop deletion reduced ER stress in these tissues and prevented dexamethasone-induced ocular hypertension. Furthermore, reduction of ER stress in the TM with sodium 4-phenylbutyrate prevented dexamethasone-induced ocular hypertension in WT mice. Our data indicate that ER stress contributes to glucocorticoid-induced ocular hypertension and suggest that reducing ER stress has potential as a therapeutic strategy for treating glucocorticoid-induced glaucoma.","[{'text': 'glaucoma', 'type': 'Disease', 'start': 44, 'end': 52, 'mesh': 'D005901'}, {'text': 'glaucoma', 'type': 'Disease', 'start': 86, 'end': 94, 'mesh': 'D005901'}, {'text': 'ocular hypertension', 'type': 'Disease', 'start': 138, 'end': 157, 'mesh': 'D009798'}, {'text': 'glaucoma', 'type': 'Disease', 'start': 229, 'end': 237, 'mesh': 'D005901'}, {'text': 'primary open-angle glaucoma', 'type': 'Disease', 'start': 253, 'end': 280, 'mesh': 'C562750'}, {'text': 'POAG', 'type': 'Disease', 'start': 282, 'end': 286, 'mesh': 'C562750'}, {'text': 'glaucoma', 'type': 'Disease', 'start': 340, 'end': 348, 'mesh': 'D005901'}, {'text': 'glaucoma', 'type': 'Disease', 'start': 486, 'end': 494, 'mesh': 'D005901'}, {'text': 'glaucoma', 'type': 'Disease', 'start': 509, 'end': 517, 'mesh': 'D005901'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 604, 'end': 617, 'mesh': 'D003907'}, {'text': 'retinal ganglion', 'type': 'Disease', 'start': 700, 'end': 716, 'mesh': 'D012173'}, {'text': 'axonal degeneration', 'type': 'Disease', 'start': 728, 'end': 747, 'mesh': 'D009410'}, {'text': 'glaucoma', 'type': 'Disease', 'start': 783, 'end': 791, 'mesh': 'D005901'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 824, 'end': 837, 'mesh': 'D003907'}, {'text': 'ocular hypertension', 'type': 'Disease', 'start': 846, 'end': 865, 'mesh': 'D009798'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 972, 'end': 985, 'mesh': 'D003907'}, {'text': 'Dexamethasone', 'type': 'Chemical', 'start': 1053, 'end': 1066, 'mesh': 'D003907'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 1240, 'end': 1253, 'mesh': 'D003907'}, {'text': 'ocular hypertension', 'type': 'Disease', 'start': 1262, 'end': 1281, 'mesh': 'D009798'}, {'text': 'sodium 4-phenylbutyrate', 'type': 'Chemical', 'start': 1334, 'end': 1357, 'mesh': 'C075773'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 1368, 'end': 1381, 'mesh': 'D003907'}, {'text': 'ocular hypertension', 'type': 'Disease', 'start': 1390, 'end': 1409, 'mesh': 'D009798'}, {'text': 'ocular hypertension', 'type': 'Disease', 'start': 1493, 'end': 1512, 'mesh': 'D009798'}, {'text': 'glaucoma', 'type': 'Disease', 'start': 1625, 'end': 1633, 'mesh': 'D005901'}]"
+1060,24709919,Effects of ginsenosides on opioid-induced hyperalgesia in mice.,"Opioid-induced hyperalgesia (OIH) is characterized by nociceptive sensitization caused by the cessation of chronic opioid use. OIH can limit the clinical use of opioid analgesics and complicate withdrawal from opioid addiction. In this study, we investigated the effects of Re, Rg1, and Rb1 ginsenosides, the bioactive components of ginseng, on OIH. OIH was achieved in mice after subcutaneous administration of morphine for 7 consecutive days three times per day. During withdrawal (days 8 and 9), these mice were administered Re, Rg1, or Rb1 intragastrically two times per day. On the test day (day 10), mice were subjected to the thermal sensitivity test and the acetic acid-induced writhing test. Re (300 mg/kg) inhibited OIH in both the thermal sensitivity test and the acetic acid-induced writhing test. However, the Rg1 and Rb1 ginsenosides failed to prevent OIH in either test. Furthermore, Rg1 showed a tendency to aggravate OIH in the acetic acid-induced writhing test. Our data suggested that the ginsenoside Re, but not Rg1 or Rb1, may contribute toward reversal of OIH.","[{'text': 'ginsenosides', 'type': 'Chemical', 'start': 11, 'end': 23, 'mesh': 'D036145'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 42, 'end': 54, 'mesh': 'D006930'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 79, 'end': 91, 'mesh': 'D006930'}, {'text': 'OIH', 'type': 'Disease', 'start': 93, 'end': 96, 'mesh': 'D006930'}, {'text': 'OIH', 'type': 'Disease', 'start': 191, 'end': 194, 'mesh': 'D006930'}, {'text': 'opioid addiction', 'type': 'Disease', 'start': 274, 'end': 290, 'mesh': 'D009293'}, {'text': 'OIH', 'type': 'Disease', 'start': 409, 'end': 412, 'mesh': 'D006930'}, {'text': 'OIH', 'type': 'Disease', 'start': 414, 'end': 417, 'mesh': 'D006930'}, {'text': 'morphine', 'type': 'Chemical', 'start': 476, 'end': 484, 'mesh': 'D009020'}, {'text': 'Re', 'type': 'Chemical', 'start': 592, 'end': 594, 'mesh': 'C049864'}, {'text': 'Rg1', 'type': 'Chemical', 'start': 596, 'end': 599, 'mesh': 'C035054'}, {'text': 'Rb1', 'type': 'Chemical', 'start': 604, 'end': 607, 'mesh': 'C442759'}, {'text': 'acetic acid', 'type': 'Chemical', 'start': 730, 'end': 741, 'mesh': 'D019342'}, {'text': 'Re', 'type': 'Chemical', 'start': 765, 'end': 767, 'mesh': 'C049864'}, {'text': 'OIH', 'type': 'Disease', 'start': 790, 'end': 793, 'mesh': 'D006930'}, {'text': 'acetic acid', 'type': 'Chemical', 'start': 839, 'end': 850, 'mesh': 'D019342'}, {'text': 'OIH', 'type': 'Disease', 'start': 930, 'end': 933, 'mesh': 'D006930'}, {'text': 'Rg1', 'type': 'Chemical', 'start': 963, 'end': 966, 'mesh': 'C035054'}, {'text': 'OIH', 'type': 'Disease', 'start': 998, 'end': 1001, 'mesh': 'D006930'}, {'text': 'acetic acid', 'type': 'Chemical', 'start': 1009, 'end': 1020, 'mesh': 'D019342'}, {'text': 'ginsenoside Re', 'type': 'Chemical', 'start': 1072, 'end': 1086, 'mesh': 'C049864'}, {'text': 'Rg1', 'type': 'Chemical', 'start': 1096, 'end': 1099, 'mesh': 'C035054'}, {'text': 'Rb1', 'type': 'Chemical', 'start': 1103, 'end': 1106, 'mesh': 'C442759'}, {'text': 'OIH', 'type': 'Disease', 'start': 1142, 'end': 1145, 'mesh': 'D006930'}]"
+1061,24717468,A comparison of severe hemodynamic disturbances between dexmedetomidine and propofol for sedation in neurocritical care patients.,"OBJECTIVE: Dexmedetomidine and propofol are commonly used sedatives in neurocritical care as they allow for frequent neurologic examinations. However, both agents are associated with significant hemodynamic side effects. The primary objective of this study is to compare the prevalence of severe hemodynamic effects in neurocritical care patients receiving dexmedetomidine and propofol. DESIGN: Multicenter, retrospective, propensity-matched cohort study. SETTING: Neurocritical care units at two academic medical centers with dedicated neurocritical care teams and board-certified neurointensivists. PATIENTS: Neurocritical care patients admitted between July 2009 and September 2012 were evaluated and then matched 1:1 based on propensity scoring of baseline characteristics. INTERVENTIONS: Continuous sedation with dexmedetomidine or propofol. MEASUREMENTS AND MAIN RESULTS: A total of 342 patients (105 dexmedetomidine and 237 propofol) were included in the analysis, with 190 matched (95 in each group) by propensity score. The primary outcome of this study was a composite of severe hypotension (mean arterial pressure < 60 mm Hg) and bradycardia (heart rate < 50 beats/min) during sedative infusion. No difference in the primary composite outcome in both the unmatched (30% vs 30%, p = 0.94) or matched cohorts (28% vs 34%, p = 0.35) could be found. When analyzed separately, no differences could be found in the prevalence of severe hypotension or bradycardia in either the unmatched or matched cohorts. CONCLUSIONS: Severe hypotension and bradycardia occur at similar prevalence in neurocritical care patients who receive dexmedetomidine or propofol. Providers should similarly consider the likelihood of hypotension or bradycardia before starting either sedative.","[{'text': 'dexmedetomidine', 'type': 'Chemical', 'start': 56, 'end': 71, 'mesh': 'D020927'}, {'text': 'propofol', 'type': 'Chemical', 'start': 76, 'end': 84, 'mesh': 'D015742'}, {'text': 'Dexmedetomidine', 'type': 'Chemical', 'start': 141, 'end': 156, 'mesh': 'D020927'}, {'text': 'propofol', 'type': 'Chemical', 'start': 161, 'end': 169, 'mesh': 'D015742'}, {'text': 'dexmedetomidine', 'type': 'Chemical', 'start': 487, 'end': 502, 'mesh': 'D020927'}, {'text': 'propofol', 'type': 'Chemical', 'start': 507, 'end': 515, 'mesh': 'D015742'}, {'text': 'dexmedetomidine', 'type': 'Chemical', 'start': 948, 'end': 963, 'mesh': 'D020927'}, {'text': 'propofol', 'type': 'Chemical', 'start': 967, 'end': 975, 'mesh': 'D015742'}, {'text': 'dexmedetomidine', 'type': 'Chemical', 'start': 1037, 'end': 1052, 'mesh': 'D020927'}, {'text': 'propofol', 'type': 'Chemical', 'start': 1061, 'end': 1069, 'mesh': 'D015742'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1219, 'end': 1230, 'mesh': 'D007022'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 1271, 'end': 1282, 'mesh': 'D001919'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1571, 'end': 1582, 'mesh': 'D007022'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 1586, 'end': 1597, 'mesh': 'D001919'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1662, 'end': 1673, 'mesh': 'D007022'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 1678, 'end': 1689, 'mesh': 'D001919'}, {'text': 'dexmedetomidine', 'type': 'Chemical', 'start': 1761, 'end': 1776, 'mesh': 'D020927'}, {'text': 'propofol', 'type': 'Chemical', 'start': 1780, 'end': 1788, 'mesh': 'D015742'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1844, 'end': 1855, 'mesh': 'D007022'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 1859, 'end': 1870, 'mesh': 'D001919'}]"
+1062,24727461,Hydroxytyrosol ameliorates oxidative stress and mitochondrial dysfunction in doxorubicin-induced cardiotoxicity in rats with breast cancer.,"Oxidative stress is involved in several processes including cancer, aging and cardiovascular disease, and has been shown to potentiate the therapeutic effect of drugs such as doxorubicin. Doxorubicin causes significant cardiotoxicity characterized by marked increases in oxidative stress and mitochondrial dysfunction. Herein, we investigate whether doxorubicin-associated chronic cardiac toxicity can be ameliorated with the antioxidant hydroxytyrosol in rats with breast cancer. Thirty-six rats bearing breast tumors induced chemically were divided into 4 groups: control, hydroxytyrosol (0.5mg/kg, 5days/week), doxorubicin (1mg/kg/week), and doxorubicin plus hydroxytyrosol. Cardiac disturbances at the cellular and mitochondrial level, mitochondrial electron transport chain complexes I-IV and apoptosis-inducing factor, and oxidative stress markers have been analyzed. Hydroxytyrosol improved the cardiac disturbances enhanced by doxorubicin by significantly reducing the percentage of altered mitochondria and oxidative damage. These results suggest that hydroxytyrosol improve the mitochondrial electron transport chain. This study demonstrates that hydroxytyrosol protect rat heart damage provoked by doxorubicin decreasing oxidative damage and mitochondrial alterations.","[{'text': 'Hydroxytyrosol', 'type': 'Chemical', 'start': 0, 'end': 14, 'mesh': 'C005975'}, {'text': 'mitochondrial dysfunction', 'type': 'Disease', 'start': 48, 'end': 73, 'mesh': 'D028361'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 77, 'end': 88, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 97, 'end': 111, 'mesh': 'D066126'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 125, 'end': 138, 'mesh': 'D001943'}, {'text': 'cancer', 'type': 'Disease', 'start': 200, 'end': 206, 'mesh': 'D009369'}, {'text': 'cardiovascular disease', 'type': 'Disease', 'start': 218, 'end': 240, 'mesh': 'D002318'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 315, 'end': 326, 'mesh': 'D004317'}, {'text': 'Doxorubicin', 'type': 'Chemical', 'start': 328, 'end': 339, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 359, 'end': 373, 'mesh': 'D066126'}, {'text': 'mitochondrial dysfunction', 'type': 'Disease', 'start': 432, 'end': 457, 'mesh': 'D028361'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 490, 'end': 501, 'mesh': 'D004317'}, {'text': 'cardiac toxicity', 'type': 'Disease', 'start': 521, 'end': 537, 'mesh': 'D066126'}, {'text': 'hydroxytyrosol', 'type': 'Chemical', 'start': 578, 'end': 592, 'mesh': 'C005975'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 606, 'end': 619, 'mesh': 'D001943'}, {'text': 'breast tumors', 'type': 'Disease', 'start': 645, 'end': 658, 'mesh': 'D001943'}, {'text': 'hydroxytyrosol', 'type': 'Chemical', 'start': 715, 'end': 729, 'mesh': 'C005975'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 754, 'end': 765, 'mesh': 'D004317'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 785, 'end': 796, 'mesh': 'D004317'}, {'text': 'hydroxytyrosol', 'type': 'Chemical', 'start': 802, 'end': 816, 'mesh': 'C005975'}, {'text': 'Cardiac disturbances', 'type': 'Disease', 'start': 818, 'end': 838, 'mesh': 'D006331'}, {'text': 'Hydroxytyrosol', 'type': 'Chemical', 'start': 1014, 'end': 1028, 'mesh': 'C005975'}, {'text': 'cardiac disturbances', 'type': 'Disease', 'start': 1042, 'end': 1062, 'mesh': 'D006331'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1075, 'end': 1086, 'mesh': 'D004317'}, {'text': 'hydroxytyrosol', 'type': 'Chemical', 'start': 1201, 'end': 1215, 'mesh': 'C005975'}, {'text': 'hydroxytyrosol', 'type': 'Chemical', 'start': 1297, 'end': 1311, 'mesh': 'C005975'}, {'text': 'heart damage', 'type': 'Disease', 'start': 1324, 'end': 1336, 'mesh': 'D006331'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1349, 'end': 1360, 'mesh': 'D004317'}]"
+1063,24729111,Amiodarone-induced myxoedema coma.,"A 62-year-old man was found to have bradycardia, hypothermia and respiratory failure 3 weeks after initiation of amiodarone therapy for atrial fibrillation. Thyroid-stimulating hormone was found to be 168 uIU/mL (nl. 0.3-5 uIU/mL) and free thyroxine (FT4) was <0.2 ng/dL (nl. 0.8-1.8 ng/dL). He received intravenous fluids, vasopressor therapy and stress dose steroids; he was intubated and admitted to the intensive care unit. He received 500 ug of intravenous levothyroxine in the first 18 h of therapy, and 150 ug intravenous daily thereafter. Haemodynamic improvement, along with complete recovery of mental status, occurred after 48 h. Twelve hours after the initiation of therapy, FT4 was 0.96 ng/dL. The patient was maintained on levothyroxine 175 (g POorally daily. A thyroid ultrasound showed diffuse heterogeneity. The 24 hour excretion of iodine was 3657 (mcg (25-756 ( mcg). The only two cases of amiodarone-induced myxoedema coma in the literature report patient death despite supportive therapy and thyroid hormone replacement. This case represents the most thoroughly investigated case of amiodarone-induced myxoedema coma with a history significant for subclinical thyroid disease.","[{'text': 'Amiodarone', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D000638'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 71, 'end': 82, 'mesh': 'D001919'}, {'text': 'hypothermia', 'type': 'Disease', 'start': 84, 'end': 95, 'mesh': 'D007035'}, {'text': 'respiratory failure', 'type': 'Disease', 'start': 100, 'end': 119, 'mesh': 'D012131'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 148, 'end': 158, 'mesh': 'D000638'}, {'text': 'atrial fibrillation', 'type': 'Disease', 'start': 171, 'end': 190, 'mesh': 'D001281'}, {'text': 'thyroxine', 'type': 'Chemical', 'start': 275, 'end': 284, 'mesh': 'D013974'}, {'text': 'steroids', 'type': 'Chemical', 'start': 395, 'end': 403, 'mesh': 'D013256'}, {'text': 'levothyroxine', 'type': 'Chemical', 'start': 497, 'end': 510, 'mesh': 'D013974'}, {'text': 'levothyroxine', 'type': 'Chemical', 'start': 772, 'end': 785, 'mesh': 'D013974'}, {'text': 'iodine', 'type': 'Chemical', 'start': 885, 'end': 891, 'mesh': 'D007455'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 944, 'end': 954, 'mesh': 'D000638'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 1139, 'end': 1149, 'mesh': 'D000638'}, {'text': 'thyroid disease', 'type': 'Disease', 'start': 1216, 'end': 1231, 'mesh': 'D013959'}]"
+1064,24733133,Use of argatroban and catheter-directed thrombolysis with alteplase in an oncology patient with heparin-induced thrombocytopenia with thrombosis.,"PURPOSE: The case of an oncology patient who developed heparin-induced thrombocytopenia with thrombosis (HITT) and was treated with argatroban plus catheter-directed thrombolysis (CDT) with alteplase is presented. SUMMARY: A 63-year-old Caucasian man with renal amyloidosis undergoing peripheral blood stem cell collection for an autologous stem cell transplant developed extensive bilateral upper-extremity deep venous thrombosis (DVT) and pulmonary embolism secondary to heparin-induced thrombocytopenia. A continuous i.v. infusion of argatroban was initiated, and the patient was managed on the general medical floor. After one week of therapy, he was transferred to the intensive care unit with cardiopulmonary compromise related to superior vena cava (SVC) syndrome. A percutaneous mechanical thrombectomy and CDT with alteplase were attempted, but the procedure was aborted due to epistaxis. The epistaxis resolved the next day, and the patient was restarted on argatroban. A second percutaneous mechanical thrombectomy was performed six days later and resulted in partial revascularization of the SVC and central veins. Postthrombectomy continuous CDT with alteplase was commenced while argatroban was withheld, and complete patency of the SVC and central veins was achieved after three days of therapy. Alteplase was discontinued, and the patient was reinitiated on argatroban; ultimately, he was transitioned to warfarin for long-term anticoagulation. Although the patient recovered, he experienced permanent vision and hearing loss, as well as end-stage renal disease. CONCLUSION: A 63-year-old man with renal amyloidosis and SVC syndrome secondary to HITT was successfully treated with argatroban and CDT with alteplase.","[{'text': 'argatroban', 'type': 'Chemical', 'start': 7, 'end': 17, 'mesh': 'C031942'}, {'text': 'thrombolysis', 'type': 'Disease', 'start': 40, 'end': 52, 'mesh': 'D055499'}, {'text': 'heparin', 'type': 'Chemical', 'start': 96, 'end': 103, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 112, 'end': 128, 'mesh': 'D013921'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 134, 'end': 144, 'mesh': 'D013927'}, {'text': 'heparin', 'type': 'Chemical', 'start': 201, 'end': 208, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 217, 'end': 233, 'mesh': 'D013921'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 239, 'end': 249, 'mesh': 'D013927'}, {'text': 'HITT', 'type': 'Disease', 'start': 251, 'end': 255, 'mesh': 'D013921|D013927'}, {'text': 'argatroban', 'type': 'Chemical', 'start': 278, 'end': 288, 'mesh': 'C031942'}, {'text': 'thrombolysis', 'type': 'Disease', 'start': 312, 'end': 324, 'mesh': 'D055499'}, {'text': 'amyloidosis', 'type': 'Disease', 'start': 408, 'end': 419, 'mesh': 'D000686'}, {'text': 'upper-extremity deep venous thrombosis', 'type': 'Disease', 'start': 538, 'end': 576, 'mesh': 'D056824'}, {'text': 'DVT', 'type': 'Disease', 'start': 578, 'end': 581, 'mesh': 'D020246'}, {'text': 'pulmonary embolism', 'type': 'Disease', 'start': 587, 'end': 605, 'mesh': 'D011655'}, {'text': 'heparin', 'type': 'Chemical', 'start': 619, 'end': 626, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 635, 'end': 651, 'mesh': 'D013921'}, {'text': 'argatroban', 'type': 'Chemical', 'start': 683, 'end': 693, 'mesh': 'C031942'}, {'text': 'superior vena cava (SVC) syndrome', 'type': 'Disease', 'start': 883, 'end': 916, 'mesh': 'D013479'}, {'text': 'epistaxis', 'type': 'Disease', 'start': 1033, 'end': 1042, 'mesh': 'D004844'}, {'text': 'epistaxis', 'type': 'Disease', 'start': 1048, 'end': 1057, 'mesh': 'D004844'}, {'text': 'argatroban', 'type': 'Chemical', 'start': 1114, 'end': 1124, 'mesh': 'C031942'}, {'text': 'argatroban', 'type': 'Chemical', 'start': 1340, 'end': 1350, 'mesh': 'C031942'}, {'text': 'argatroban', 'type': 'Chemical', 'start': 1520, 'end': 1530, 'mesh': 'C031942'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 1567, 'end': 1575, 'mesh': 'D014859'}, {'text': 'end-stage renal disease', 'type': 'Disease', 'start': 1700, 'end': 1723, 'mesh': 'D007676'}, {'text': 'amyloidosis', 'type': 'Disease', 'start': 1766, 'end': 1777, 'mesh': 'D000686'}, {'text': 'SVC syndrome', 'type': 'Disease', 'start': 1782, 'end': 1794, 'mesh': 'D013479'}, {'text': 'HITT', 'type': 'Disease', 'start': 1808, 'end': 1812, 'mesh': 'D013921|D013927'}, {'text': 'argatroban', 'type': 'Chemical', 'start': 1843, 'end': 1853, 'mesh': 'C031942'}]"
+1065,24739405,Effects of dehydroepiandrosterone in amphetamine-induced schizophrenia models in mice.,"OBJECTIVE: To examine the effects of dehydroepiandrosterone (DHEA) on animal models of schizophrenia. METHODS: Seventy Swiss albino female mice (25-35 g) were divided into 4 groups: amphetamine-free (control), amphetamine, 50, and 100 mg/kg DHEA. The DHEA was administered intraperitoneally (ip) for 5 days. Amphetamine (3 mg/kg ip) induced hyper locomotion, apomorphine (1.5 mg/kg subcutaneously [sc]) induced climbing, and haloperidol (1.5 mg/kg sc) induced catalepsy tests were used as animal models of schizophrenia. The study was conducted at the Animal Experiment Laboratories, Department of Pharmacology, Medical School, Eskisehir Osmangazi University, Eskisehir, Turkey between March and May 2012. Statistical analysis was carried out using Kruskal-Wallis test for hyper locomotion, and one-way ANOVA for climbing and catalepsy tests. RESULTS: In the amphetamine-induced locomotion test, there were significant increases in all movements compared with the amphetamine-free group. Both DHEA 50 mg/kg (p<0.05), and 100 mg/kg (p<0.01) significantly decreased all movements compared with the amphetamine-induced locomotion group. There was a significant difference between groups in the haloperidol-induced catalepsy test (p<0.05). There was no significant difference between groups in terms of total climbing time in the apomorphine-induced climbing test (p>0.05). CONCLUSION: We observed that DHEA reduced locomotor activity and increased catalepsy at both doses, while it had no effect on climbing behavior. We suggest that DHEA displays typical neuroleptic-like effects, and may be used in the treatment of schizophrenia.","[{'text': 'dehydroepiandrosterone', 'type': 'Chemical', 'start': 11, 'end': 33, 'mesh': 'D003687'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 37, 'end': 48, 'mesh': 'D000661'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 57, 'end': 70, 'mesh': 'D012559'}, {'text': 'dehydroepiandrosterone', 'type': 'Chemical', 'start': 124, 'end': 146, 'mesh': 'D003687'}, {'text': 'DHEA', 'type': 'Chemical', 'start': 148, 'end': 152, 'mesh': 'D003687'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 174, 'end': 187, 'mesh': 'D012559'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 269, 'end': 280, 'mesh': 'D000661'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 297, 'end': 308, 'mesh': 'D000661'}, {'text': 'DHEA', 'type': 'Chemical', 'start': 328, 'end': 332, 'mesh': 'D003687'}, {'text': 'DHEA', 'type': 'Chemical', 'start': 338, 'end': 342, 'mesh': 'D003687'}, {'text': 'Amphetamine', 'type': 'Chemical', 'start': 395, 'end': 406, 'mesh': 'D000661'}, {'text': 'hyper', 'type': 'Disease', 'start': 428, 'end': 433, 'mesh': 'D006948'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 446, 'end': 457, 'mesh': 'D001058'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 512, 'end': 523, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 547, 'end': 556, 'mesh': 'D002375'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 593, 'end': 606, 'mesh': 'D012559'}, {'text': 'hyper', 'type': 'Disease', 'start': 860, 'end': 865, 'mesh': 'D006948'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 913, 'end': 922, 'mesh': 'D002375'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 946, 'end': 957, 'mesh': 'D000661'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1051, 'end': 1062, 'mesh': 'D000661'}, {'text': 'DHEA', 'type': 'Chemical', 'start': 1080, 'end': 1084, 'mesh': 'D003687'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1183, 'end': 1194, 'mesh': 'D000661'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1278, 'end': 1289, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 1298, 'end': 1307, 'mesh': 'D002375'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 1413, 'end': 1424, 'mesh': 'D001058'}, {'text': 'DHEA', 'type': 'Chemical', 'start': 1486, 'end': 1490, 'mesh': 'D003687'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 1532, 'end': 1541, 'mesh': 'D002375'}, {'text': 'DHEA', 'type': 'Chemical', 'start': 1618, 'end': 1622, 'mesh': 'D003687'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 1702, 'end': 1715, 'mesh': 'D012559'}]"
+1066,24742750,Availability of human induced pluripotent stem cell-derived cardiomyocytes in assessment of drug potential for QT prolongation.,"Field potential duration (FPD) in human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), which can express QT interval in an electrocardiogram, is reported to be a useful tool to predict K(+) channel and Ca(2+) channel blocker effects on QT interval. However, there is no report showing that this technique can be used to predict multichannel blocker potential for QT prolongation. The aim of this study is to show that FPD from MEA (Multielectrode array) of hiPS-CMs can detect QT prolongation induced by multichannel blockers. hiPS-CMs were seeded onto MEA and FPD was measured for 2min every 10min for 30min after drug exposure for the vehicle and each drug concentration. IKr and IKs blockers concentration-dependently prolonged corrected FPD (FPDc), whereas Ca(2+) channel blockers concentration-dependently shortened FPDc. Also, the multichannel blockers Amiodarone, Paroxetine, Terfenadine and Citalopram prolonged FPDc in a concentration dependent manner. Finally, the IKr blockers, Terfenadine and Citalopram, which are reported to cause Torsade de Pointes (TdP) in clinical practice, produced early afterdepolarization (EAD). hiPS-CMs using MEA system and FPDc can predict the effects of drug candidates on QT interval. This study also shows that this assay can help detect EAD for drugs with TdP potential.","[{'text': 'QT prolongation', 'type': 'Disease', 'start': 111, 'end': 126, 'mesh': 'D008133'}, {'text': 'K', 'type': 'Chemical', 'start': 331, 'end': 332, 'mesh': 'D011188'}, {'text': 'Ca', 'type': 'Chemical', 'start': 348, 'end': 350, 'mesh': 'D002118'}, {'text': 'QT prolongation', 'type': 'Disease', 'start': 509, 'end': 524, 'mesh': 'D008133'}, {'text': 'QT prolongation', 'type': 'Disease', 'start': 623, 'end': 638, 'mesh': 'D008133'}, {'text': 'Ca', 'type': 'Chemical', 'start': 907, 'end': 909, 'mesh': 'D002118'}, {'text': 'Amiodarone', 'type': 'Chemical', 'start': 1005, 'end': 1015, 'mesh': 'D000638'}, {'text': 'Paroxetine', 'type': 'Chemical', 'start': 1017, 'end': 1027, 'mesh': 'D017374'}, {'text': 'Terfenadine', 'type': 'Chemical', 'start': 1029, 'end': 1040, 'mesh': 'D016593'}, {'text': 'Citalopram', 'type': 'Chemical', 'start': 1045, 'end': 1055, 'mesh': 'D015283'}, {'text': 'Terfenadine', 'type': 'Chemical', 'start': 1135, 'end': 1146, 'mesh': 'D016593'}, {'text': 'Citalopram', 'type': 'Chemical', 'start': 1151, 'end': 1161, 'mesh': 'D015283'}, {'text': 'Torsade de Pointes', 'type': 'Disease', 'start': 1191, 'end': 1209, 'mesh': 'D016171'}, {'text': 'TdP', 'type': 'Disease', 'start': 1211, 'end': 1214, 'mesh': 'D016171'}, {'text': 'TdP', 'type': 'Disease', 'start': 1447, 'end': 1450, 'mesh': 'D016171'}]"
+1067,24753331,Dermal developmental toxicity of N-phenylimide herbicides in rats.,"BACKGROUND: S-53482 and S-23121 are N-phenylimide herbicides and produced embryolethality, teratogenicity (mainly ventricular septal defects and wavy ribs), and growth retardation in rats in conventional oral developmental toxicity studies. Our objective in this study was to investigate whether the compounds induce developmental toxicity via the dermal route, which is more relevant to occupational exposure, hence better addressing human health risks. METHODS: S-53482 was administered dermally to rats at 30, 100, and 300 mg/kg during organogenesis, and S-23121 was administered at 200, 400, and 800 mg/kg (the maximum applicable dose level). Fetuses were obtained by a Cesarean section and examined for external, visceral, and skeletal alterations. RESULTS: Dermal exposure of rats to S-53482 at 300 mg/kg produced patterns of developmental toxicity similar to those resulting from oral exposure. Toxicity included embryolethality, teratogenicity, and growth retardation. Dermal administration of S-23121 at 800 mg/kg resulted in an increased incidence of embryonic death and ventricular septal defect, but retarded fetal growth was not observed as it was following oral exposure to S-23121. CONCLUSIONS: Based on the results, S-53482 and S-23121 were teratogenic when administered dermally to pregnant rats as were the compounds administered orally. Thus, investigation of the mechanism and its human relevancy become more important.","[{'text': 'toxicity', 'type': 'Disease', 'start': 21, 'end': 29, 'mesh': 'D064420'}, {'text': 'S-53482', 'type': 'Chemical', 'start': 79, 'end': 86, 'mesh': 'C106487'}, {'text': 'S-23121', 'type': 'Chemical', 'start': 91, 'end': 98, 'mesh': 'C083440'}, {'text': 'embryolethality', 'type': 'Disease', 'start': 141, 'end': 156, 'mesh': 'D020964'}, {'text': 'teratogenicity', 'type': 'Disease', 'start': 158, 'end': 172, 'mesh': 'D064793'}, {'text': 'ventricular septal defects', 'type': 'Disease', 'start': 181, 'end': 207, 'mesh': 'D006345'}, {'text': 'growth retardation', 'type': 'Disease', 'start': 228, 'end': 246, 'mesh': 'D005317'}, {'text': 'toxicity', 'type': 'Disease', 'start': 290, 'end': 298, 'mesh': 'D064420'}, {'text': 'toxicity', 'type': 'Disease', 'start': 398, 'end': 406, 'mesh': 'D064420'}, {'text': 'S-53482', 'type': 'Chemical', 'start': 531, 'end': 538, 'mesh': 'C106487'}, {'text': 'S-23121', 'type': 'Chemical', 'start': 625, 'end': 632, 'mesh': 'C083440'}, {'text': 'S-53482', 'type': 'Chemical', 'start': 857, 'end': 864, 'mesh': 'C106487'}, {'text': 'toxicity', 'type': 'Disease', 'start': 913, 'end': 921, 'mesh': 'D064420'}, {'text': 'Toxicity', 'type': 'Disease', 'start': 969, 'end': 977, 'mesh': 'D064420'}, {'text': 'embryolethality', 'type': 'Disease', 'start': 987, 'end': 1002, 'mesh': 'D020964'}, {'text': 'teratogenicity', 'type': 'Disease', 'start': 1004, 'end': 1018, 'mesh': 'D064793'}, {'text': 'growth retardation', 'type': 'Disease', 'start': 1024, 'end': 1042, 'mesh': 'D005317'}, {'text': 'S-23121', 'type': 'Chemical', 'start': 1069, 'end': 1076, 'mesh': 'C083440'}, {'text': 'embryonic death', 'type': 'Disease', 'start': 1128, 'end': 1143, 'mesh': 'D020964'}, {'text': 'ventricular septal defect', 'type': 'Disease', 'start': 1148, 'end': 1173, 'mesh': 'D006345'}, {'text': 'S-23121', 'type': 'Chemical', 'start': 1255, 'end': 1262, 'mesh': 'C083440'}, {'text': 'S-53482', 'type': 'Chemical', 'start': 1299, 'end': 1306, 'mesh': 'C106487'}, {'text': 'S-23121', 'type': 'Chemical', 'start': 1311, 'end': 1318, 'mesh': 'C083440'}, {'text': 'teratogenic', 'type': 'Disease', 'start': 1324, 'end': 1335, 'mesh': 'D064793'}]"
+1068,24778426,Rates of Renal Toxicity in Cancer Patients Receiving Cisplatin With and Without Mannitol.,"BACKGROUND: Cisplatin is a widely used antineoplastic. One of the major complications of cisplatin use is dose-limiting nephrotoxicity. There are many strategies to prevent this toxicity, including the use of mannitol as a nephroprotectant in combination with hydration. OBJECTIVE: We aimed to evaluate the rates of cisplatin-induced nephrotoxicity in cancer patients receiving single-agent cisplatin with and without mannitol. METHODS: This single-center retrospective analysis was a quasi experiment created by the national mannitol shortage. Data were collected on adult cancer patients receiving single-agent cisplatin as an outpatient from January 2011 to September 2012. The primary outcome was acute kidney injury (AKI). RESULTS: We evaluated 143 patients who received single-agent cisplatin; 97.2% of patients had head and neck cancer as their primary malignancy. Patients who did not receive mannitol were more likely to develop nephrotoxicity: odds ratio [OR] = 2.646 (95% CI = 1.008, 6.944; P = 0.048). Patients who received the 100 mg/m(2) dosing and patients who had a history of hypertension also had a higher likelihood of developing nephrotoxicity: OR = 11.494 (95% CI = 4.149, 32.258; P < 0.0001) and OR = 3.219 (95% CI = 1.228, 8.439; P = 0.017), respectively. CONCLUSIONS: When limited quantities of mannitol are available, it should preferentially be given to patients at particularly high risk of nephrotoxicity. Our analysis suggests that those patients receiving the dosing schedule of 100 mg/m(2) cisplatin every 3 weeks and those with hypertension are at the greatest risk of nephrotoxicity and would benefit from the addition of mannitol.","[{'text': 'Renal Toxicity', 'type': 'Disease', 'start': 9, 'end': 23, 'mesh': 'D007674'}, {'text': 'Cancer', 'type': 'Disease', 'start': 27, 'end': 33, 'mesh': 'D009369'}, {'text': 'Cisplatin', 'type': 'Chemical', 'start': 53, 'end': 62, 'mesh': 'D002945'}, {'text': 'Mannitol', 'type': 'Chemical', 'start': 80, 'end': 88, 'mesh': 'D008353'}, {'text': 'Cisplatin', 'type': 'Chemical', 'start': 102, 'end': 111, 'mesh': 'D002945'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 179, 'end': 188, 'mesh': 'D002945'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 210, 'end': 224, 'mesh': 'D007674'}, {'text': 'toxicity', 'type': 'Disease', 'start': 268, 'end': 276, 'mesh': 'D064420'}, {'text': 'mannitol', 'type': 'Chemical', 'start': 299, 'end': 307, 'mesh': 'D008353'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 406, 'end': 415, 'mesh': 'D002945'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 424, 'end': 438, 'mesh': 'D007674'}, {'text': 'cancer', 'type': 'Disease', 'start': 442, 'end': 448, 'mesh': 'D009369'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 481, 'end': 490, 'mesh': 'D002945'}, {'text': 'mannitol', 'type': 'Chemical', 'start': 508, 'end': 516, 'mesh': 'D008353'}, {'text': 'mannitol', 'type': 'Chemical', 'start': 616, 'end': 624, 'mesh': 'D008353'}, {'text': 'cancer', 'type': 'Disease', 'start': 664, 'end': 670, 'mesh': 'D009369'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 703, 'end': 712, 'mesh': 'D002945'}, {'text': 'acute kidney injury', 'type': 'Disease', 'start': 791, 'end': 810, 'mesh': 'D058186'}, {'text': 'AKI', 'type': 'Disease', 'start': 812, 'end': 815, 'mesh': 'D058186'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 879, 'end': 888, 'mesh': 'D002945'}, {'text': 'head and neck cancer', 'type': 'Disease', 'start': 912, 'end': 932, 'mesh': 'D006258'}, {'text': 'malignancy', 'type': 'Disease', 'start': 950, 'end': 960, 'mesh': 'D009369'}, {'text': 'mannitol', 'type': 'Chemical', 'start': 991, 'end': 999, 'mesh': 'D008353'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1028, 'end': 1042, 'mesh': 'D007674'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1183, 'end': 1195, 'mesh': 'D006973'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1239, 'end': 1253, 'mesh': 'D007674'}, {'text': 'mannitol', 'type': 'Chemical', 'start': 1409, 'end': 1417, 'mesh': 'D008353'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1508, 'end': 1522, 'mesh': 'D007674'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 1611, 'end': 1620, 'mesh': 'D002945'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1650, 'end': 1662, 'mesh': 'D006973'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1691, 'end': 1705, 'mesh': 'D007674'}, {'text': 'mannitol', 'type': 'Chemical', 'start': 1745, 'end': 1753, 'mesh': 'D008353'}]"
+1069,24802403,"Metformin protects against seizures, learning and memory impairments and oxidative damage induced by pentylenetetrazole-induced kindling in mice.","Cognitive impairment, the most common and severe comorbidity of epilepsy, greatly diminishes the quality of life. However, current therapeutic interventions for epilepsy can also cause untoward cognitive effects. Thus, there is an urgent need for new kinds of agents targeting both seizures and cognition deficits. Oxidative stress is considered to play an important role in epileptogenesis and cognitive deficits, and antioxidants have a putative antiepileptic potential. Metformin, the most commonly prescribed antidiabetic oral drug, has antioxidant properties. This study was designed to evaluate the ameliorative effects of metformin on seizures, cognitive impairment and brain oxidative stress markers observed in pentylenetetrazole-induced kindling animals. Male C57BL/6 mice were administered with subconvulsive dose of pentylenetetrazole (37 mg/kg, i.p.) every other day for 14 injections. Metformin was injected intraperitoneally in dose of 200mg/kg along with alternate-day PTZ. We found that metformin suppressed the progression of kindling, ameliorated the cognitive impairment and decreased brain oxidative stress. Thus the present study concluded that metformin may be a potential agent for the treatment of epilepsy as well as a protective medicine against cognitive impairment induced by seizures.","[{'text': 'Metformin', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D008687'}, {'text': 'seizures', 'type': 'Disease', 'start': 27, 'end': 35, 'mesh': 'D012640'}, {'text': 'pentylenetetrazole', 'type': 'Chemical', 'start': 101, 'end': 119, 'mesh': 'D010433'}, {'text': 'Cognitive impairment', 'type': 'Disease', 'start': 146, 'end': 166, 'mesh': 'D003072'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 210, 'end': 218, 'mesh': 'D004827'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 307, 'end': 315, 'mesh': 'D004827'}, {'text': 'seizures', 'type': 'Disease', 'start': 428, 'end': 436, 'mesh': 'D012640'}, {'text': 'cognition deficits', 'type': 'Disease', 'start': 441, 'end': 459, 'mesh': 'D003072'}, {'text': 'cognitive deficits', 'type': 'Disease', 'start': 541, 'end': 559, 'mesh': 'D003072'}, {'text': 'Metformin', 'type': 'Chemical', 'start': 619, 'end': 628, 'mesh': 'D008687'}, {'text': 'metformin', 'type': 'Chemical', 'start': 775, 'end': 784, 'mesh': 'D008687'}, {'text': 'seizures', 'type': 'Disease', 'start': 788, 'end': 796, 'mesh': 'D012640'}, {'text': 'cognitive impairment', 'type': 'Disease', 'start': 798, 'end': 818, 'mesh': 'D003072'}, {'text': 'pentylenetetrazole', 'type': 'Chemical', 'start': 866, 'end': 884, 'mesh': 'D010433'}, {'text': 'pentylenetetrazole', 'type': 'Chemical', 'start': 974, 'end': 992, 'mesh': 'D010433'}, {'text': 'Metformin', 'type': 'Chemical', 'start': 1045, 'end': 1054, 'mesh': 'D008687'}, {'text': 'PTZ', 'type': 'Chemical', 'start': 1131, 'end': 1134, 'mesh': 'D010433'}, {'text': 'metformin', 'type': 'Chemical', 'start': 1150, 'end': 1159, 'mesh': 'D008687'}, {'text': 'cognitive impairment', 'type': 'Disease', 'start': 1216, 'end': 1236, 'mesh': 'D003072'}, {'text': 'metformin', 'type': 'Chemical', 'start': 1313, 'end': 1322, 'mesh': 'D008687'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 1369, 'end': 1377, 'mesh': 'D004827'}, {'text': 'cognitive impairment', 'type': 'Disease', 'start': 1419, 'end': 1439, 'mesh': 'D003072'}, {'text': 'seizures', 'type': 'Disease', 'start': 1451, 'end': 1459, 'mesh': 'D012640'}]"
+1070,24812279,P53 inhibition exacerbates late-stage anthracycline cardiotoxicity.,"AIMS: Doxorubicin (DOX) is an effective anti-cancer therapeutic, but is associated with both acute and late-stage cardiotoxicity. Children are particularly sensitive to DOX-induced heart failure. Here, the impact of p53 inhibition on acute vs. late-stage DOX cardiotoxicity was examined in a juvenile model. METHODS AND RESULTS: Two-week-old MHC-CB7 mice (which express dominant-interfering p53 in cardiomyocytes) and their non-transgenic (NON-TXG) littermates received weekly DOX injections for 5 weeks (25 mg/kg cumulative dose). One week after the last DOX treatment (acute stage), MHC-CB7 mice exhibited improved cardiac function and lower levels of cardiomyocyte apoptosis when compared with the NON-TXG mice. Surprisingly, by 13 weeks following the last DOX treatment (late stage), MHC-CB7 exhibited a progressive decrease in cardiac function and higher rates of cardiomyocyte apoptosis when compared with NON-TXG mice. p53 inhibition blocked transient DOX-induced STAT3 activation in MHC-CB7 mice, which was associated with enhanced induction of the DNA repair proteins Ku70 and Ku80. Mice with cardiomyocyte-restricted deletion of STAT3 exhibited worse cardiac function, higher levels of cardiomyocyte apoptosis, and a greater induction of Ku70 and Ku80 in response to DOX treatment during the acute stage when compared with control animals. CONCLUSION: These data support a model wherein a p53-dependent cardioprotective pathway, mediated via STAT3 activation, mitigates DOX-induced myocardial stress during drug delivery. Furthermore, these data suggest an explanation as to how p53 inhibition can result in cardioprotection during drug treatment and, paradoxically, enhanced cardiotoxicity long after the cessation of drug treatment.","[{'text': 'anthracycline', 'type': 'Chemical', 'start': 38, 'end': 51, 'mesh': 'D018943'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 52, 'end': 66, 'mesh': 'D066126'}, {'text': 'Doxorubicin', 'type': 'Chemical', 'start': 74, 'end': 85, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 87, 'end': 90, 'mesh': 'D004317'}, {'text': 'cancer', 'type': 'Disease', 'start': 113, 'end': 119, 'mesh': 'D009369'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 182, 'end': 196, 'mesh': 'D066126'}, {'text': 'DOX', 'type': 'Chemical', 'start': 237, 'end': 240, 'mesh': 'D004317'}, {'text': 'heart failure', 'type': 'Disease', 'start': 249, 'end': 262, 'mesh': 'D006333'}, {'text': 'DOX', 'type': 'Chemical', 'start': 323, 'end': 326, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 327, 'end': 341, 'mesh': 'D066126'}, {'text': 'DOX', 'type': 'Chemical', 'start': 545, 'end': 548, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 624, 'end': 627, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 828, 'end': 831, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1027, 'end': 1030, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1345, 'end': 1348, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1548, 'end': 1551, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1754, 'end': 1768, 'mesh': 'D066126'}]"
+1071,24816962,Metronidazole-induced encephalopathy: an uncommon scenario.,Metronidazole can produce neurological complications although it is not a common scenario. We present a case where a patient developed features of encephalopathy following prolonged metronidazole intake. Magnetic resonance imaging (MRI) brain showed abnormal signal intensity involving both dentate nuclei of cerebellum and splenium of corpus callosum. The diagnosis of metronidazole toxicity was made by the MRI findings and supported clinically.,"[{'text': 'Metronidazole', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'D008795'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 22, 'end': 36, 'mesh': 'D001927'}, {'text': 'Metronidazole', 'type': 'Chemical', 'start': 60, 'end': 73, 'mesh': 'D008795'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 207, 'end': 221, 'mesh': 'D001927'}, {'text': 'metronidazole', 'type': 'Chemical', 'start': 242, 'end': 255, 'mesh': 'D008795'}, {'text': 'metronidazole', 'type': 'Chemical', 'start': 430, 'end': 443, 'mesh': 'D008795'}, {'text': 'toxicity', 'type': 'Disease', 'start': 444, 'end': 452, 'mesh': 'D064420'}]"
+1072,24840785,Aconitine-induced Ca2+ overload causes arrhythmia and triggers apoptosis through p38 MAPK signaling pathway in rats.,"Aconitine is a major bioactive diterpenoid alkaloid with high content derived from herbal aconitum plants. Emerging evidence indicates that voltage-dependent Na(+) channels have pivotal roles in the cardiotoxicity of aconitine. However, no reports are available on the role of Ca(2+) in aconitine poisoning. In this study, we explored the importance of pathological Ca(2+) signaling in aconitine poisoning in vitro and in vivo. We found that Ca(2+) overload lead to accelerated beating rhythm in adult rat ventricular myocytes and caused arrhythmia in conscious freely moving rats. To investigate effects of aconitine on myocardial injury, we performed cytotoxicity assay in neonatal rat ventricular myocytes (NRVMs), as well as measured lactate dehydrogenase level in the culture medium of NRVMs and activities of serum cardiac enzymes in rats. The results showed that aconitine resulted in myocardial injury and reduced NRVMs viability dose-dependently. To confirm the pro-apoptotic effects, we performed flow cytometric detection, cardiac histology, transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. The results showed that aconitine stimulated apoptosis time-dependently. The expression analysis of Ca(2+) handling proteins demonstrated that aconitine promoted Ca(2+) overload through the expression regulation of Ca(2+) handling proteins. The expression analysis of apoptosis-related proteins revealed that pro-apoptotic protein expression was upregulated, and anti-apoptotic protein BCL-2 expression was downregulated. Furthermore, increased phosphorylation of MAPK family members, especially the P-P38/P38 ratio was found in cardiac tissues. Hence, our results suggest that aconitine significantly aggravates Ca(2+) overload and causes arrhythmia and finally promotes apoptotic development via phosphorylation of P38 mitogen-activated protein kinase.","[{'text': 'Aconitine', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D000157'}, {'text': 'Ca', 'type': 'Chemical', 'start': 18, 'end': 20, 'mesh': 'D002118'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 39, 'end': 49, 'mesh': 'D001145'}, {'text': 'Aconitine', 'type': 'Chemical', 'start': 117, 'end': 126, 'mesh': 'D000157'}, {'text': 'Na', 'type': 'Chemical', 'start': 275, 'end': 277, 'mesh': 'D012964'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 316, 'end': 330, 'mesh': 'D066126'}, {'text': 'aconitine', 'type': 'Chemical', 'start': 334, 'end': 343, 'mesh': 'D000157'}, {'text': 'Ca', 'type': 'Chemical', 'start': 394, 'end': 396, 'mesh': 'D002118'}, {'text': 'aconitine', 'type': 'Chemical', 'start': 404, 'end': 413, 'mesh': 'D000157'}, {'text': 'poisoning', 'type': 'Disease', 'start': 414, 'end': 423, 'mesh': 'D011041'}, {'text': 'Ca', 'type': 'Chemical', 'start': 483, 'end': 485, 'mesh': 'D002118'}, {'text': 'aconitine', 'type': 'Chemical', 'start': 503, 'end': 512, 'mesh': 'D000157'}, {'text': 'poisoning', 'type': 'Disease', 'start': 513, 'end': 522, 'mesh': 'D011041'}, {'text': 'Ca', 'type': 'Chemical', 'start': 559, 'end': 561, 'mesh': 'D002118'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 655, 'end': 665, 'mesh': 'D001145'}, {'text': 'aconitine', 'type': 'Chemical', 'start': 725, 'end': 734, 'mesh': 'D000157'}, {'text': 'myocardial injury', 'type': 'Disease', 'start': 738, 'end': 755, 'mesh': 'D009202'}, {'text': 'cytotoxicity', 'type': 'Disease', 'start': 770, 'end': 782, 'mesh': 'D064420'}, {'text': 'lactate', 'type': 'Chemical', 'start': 855, 'end': 862, 'mesh': 'D019344'}, {'text': 'aconitine', 'type': 'Chemical', 'start': 987, 'end': 996, 'mesh': 'D000157'}, {'text': 'myocardial injury', 'type': 'Disease', 'start': 1009, 'end': 1026, 'mesh': 'D009202'}, {'text': 'dUTP', 'type': 'Chemical', 'start': 1254, 'end': 1258, 'mesh': '-1'}, {'text': 'biotin', 'type': 'Chemical', 'start': 1259, 'end': 1265, 'mesh': 'D001710'}, {'text': 'aconitine', 'type': 'Chemical', 'start': 1315, 'end': 1324, 'mesh': 'D000157'}, {'text': 'Ca', 'type': 'Chemical', 'start': 1391, 'end': 1393, 'mesh': 'D002118'}, {'text': 'aconitine', 'type': 'Chemical', 'start': 1434, 'end': 1443, 'mesh': 'D000157'}, {'text': 'Ca', 'type': 'Chemical', 'start': 1453, 'end': 1455, 'mesh': 'D002118'}, {'text': 'Ca', 'type': 'Chemical', 'start': 1506, 'end': 1508, 'mesh': 'D002118'}, {'text': 'aconitine', 'type': 'Chemical', 'start': 1869, 'end': 1878, 'mesh': 'D000157'}, {'text': 'Ca', 'type': 'Chemical', 'start': 1904, 'end': 1906, 'mesh': 'D002118'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 1931, 'end': 1941, 'mesh': 'D001145'}]"
+1073,24842192,Chronic treatment with metformin suppresses toll-like receptor 4 signaling and attenuates left ventricular dysfunction following myocardial infarction.,"Acute treatment with metformin has a protective effect in myocardial infarction by suppression of inflammatory responses due to activation of AMP-activated protein kinase (AMPK). In the present study, the effect of chronic pre-treatment with metformin on cardiac dysfunction and toll-like receptor 4 (TLR4) activities following myocardial infarction and their relation with AMPK were assessed. Male Wistar rats were randomly assigned to one of 5 groups (n=6): normal control and groups were injected isoproterenol after chronic pre-treatment with 0, 25, 50, or 100mg/kg of metformin twice daily for 14 days. Isoproterenol (100mg/kg) was injected subcutaneously on the 13th and 14th days to induce acute myocardial infarction. Isoproterenol alone decreased left ventricular systolic pressure and myocardial contractility indexed as LVdp/dtmax and LVdp/dtmin. The left ventricular dysfunction was significantly lower in the groups treated with 25 and 50mg/kg of metformin. Metfromin markedly lowered isoproterenol-induced elevation in the levels of TLR4 mRNA, myeloid differentiation protein 88 (MyD88), tumor necrosis factor-alpha (TNF-a), and interleukin 6 (IL-6) in the heart tissues. Similar changes were also seen in the serum levels of TNF-a and IL-6. However, the lower doses of 25 and 50mg/kg were more effective than 100mg/kg. Phosphorylated AMPKa (p-AMPK) in the myocardium was significantly elevated by 25mg/kg of metformin, slightly by 50mg/kg, but not by 100mg/kg. Chronic pre-treatment with metformin reduces post-myocardial infarction cardiac dysfunction and suppresses inflammatory responses, possibly through inhibition of TLR4 activities. This mechanism can be considered as a target to protect infarcted myocardium.","[{'text': 'metformin', 'type': 'Chemical', 'start': 23, 'end': 32, 'mesh': 'D008687'}, {'text': 'left ventricular dysfunction', 'type': 'Disease', 'start': 90, 'end': 118, 'mesh': 'D018487'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 129, 'end': 150, 'mesh': 'D009203'}, {'text': 'metformin', 'type': 'Chemical', 'start': 173, 'end': 182, 'mesh': 'D008687'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 210, 'end': 231, 'mesh': 'D009203'}, {'text': 'AMP', 'type': 'Chemical', 'start': 294, 'end': 297, 'mesh': 'D000667'}, {'text': 'metformin', 'type': 'Chemical', 'start': 394, 'end': 403, 'mesh': 'D008687'}, {'text': 'cardiac dysfunction', 'type': 'Disease', 'start': 407, 'end': 426, 'mesh': 'D006331'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 480, 'end': 501, 'mesh': 'D009203'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 652, 'end': 665, 'mesh': 'D007545'}, {'text': 'metformin', 'type': 'Chemical', 'start': 725, 'end': 734, 'mesh': 'D008687'}, {'text': 'Isoproterenol', 'type': 'Chemical', 'start': 760, 'end': 773, 'mesh': 'D007545'}, {'text': 'acute myocardial infarction', 'type': 'Disease', 'start': 849, 'end': 876, 'mesh': 'D009203'}, {'text': 'Isoproterenol', 'type': 'Chemical', 'start': 878, 'end': 891, 'mesh': 'D007545'}, {'text': 'left ventricular dysfunction', 'type': 'Disease', 'start': 1014, 'end': 1042, 'mesh': 'D018487'}, {'text': 'metformin', 'type': 'Chemical', 'start': 1112, 'end': 1121, 'mesh': 'D008687'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1150, 'end': 1163, 'mesh': 'D007545'}, {'text': 'tumor', 'type': 'Disease', 'start': 1254, 'end': 1259, 'mesh': 'D009369'}, {'text': 'necrosis', 'type': 'Disease', 'start': 1260, 'end': 1268, 'mesh': 'D009336'}, {'text': 'metformin', 'type': 'Chemical', 'start': 1575, 'end': 1584, 'mesh': 'D008687'}, {'text': 'metformin', 'type': 'Chemical', 'start': 1655, 'end': 1664, 'mesh': 'D008687'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 1678, 'end': 1699, 'mesh': 'D009203'}]"
+1074,24881749,Neuroleptic malignant syndrome induced by combination therapy with tetrabenazine and tiapride in a Japanese patient with Huntington's disease at the terminal stage of recurrent breast cancer.,"We herein describe the case of an 81-year-old Japanese woman with neuroleptic malignant syndrome that occurred 36 days after the initiation of combination therapy with tiapride (75 mg/day) and tetrabenazine (12.5 mg/day) for Huntington's disease. The patient had been treated with tiapride or tetrabenazine alone without any adverse effects before the administration of the combination therapy. She also had advanced breast cancer when the combination therapy was initiated. To the best of our knowledge, the occurrence of neuroleptic malignant syndrome due to combination therapy with tetrabenazine and tiapride has not been previously reported. Tetrabenazine should be administered very carefully in combination with other neuroleptic drugs, particularly in patients with a worsening general condition.","[{'text': 'Neuroleptic malignant syndrome', 'type': 'Disease', 'start': 0, 'end': 30, 'mesh': 'D009459'}, {'text': 'tetrabenazine', 'type': 'Chemical', 'start': 67, 'end': 80, 'mesh': 'D013747'}, {'text': 'tiapride', 'type': 'Chemical', 'start': 85, 'end': 93, 'mesh': 'D063325'}, {'text': ""Huntington's disease"", 'type': 'Disease', 'start': 121, 'end': 141, 'mesh': 'D006816'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 177, 'end': 190, 'mesh': 'D001943'}, {'text': 'neuroleptic malignant syndrome', 'type': 'Disease', 'start': 258, 'end': 288, 'mesh': 'D009459'}, {'text': 'tiapride', 'type': 'Chemical', 'start': 360, 'end': 368, 'mesh': 'D063325'}, {'text': 'tetrabenazine', 'type': 'Chemical', 'start': 385, 'end': 398, 'mesh': 'D013747'}, {'text': ""Huntington's disease"", 'type': 'Disease', 'start': 417, 'end': 437, 'mesh': 'D006816'}, {'text': 'tiapride', 'type': 'Chemical', 'start': 473, 'end': 481, 'mesh': 'D063325'}, {'text': 'tetrabenazine', 'type': 'Chemical', 'start': 485, 'end': 498, 'mesh': 'D013747'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 609, 'end': 622, 'mesh': 'D001943'}, {'text': 'neuroleptic malignant syndrome', 'type': 'Disease', 'start': 715, 'end': 745, 'mesh': 'D009459'}, {'text': 'tetrabenazine', 'type': 'Chemical', 'start': 778, 'end': 791, 'mesh': 'D013747'}, {'text': 'tiapride', 'type': 'Chemical', 'start': 796, 'end': 804, 'mesh': 'D063325'}, {'text': 'Tetrabenazine', 'type': 'Chemical', 'start': 839, 'end': 852, 'mesh': 'D013747'}, {'text': 'neuroleptic drugs', 'type': 'Chemical', 'start': 917, 'end': 934, 'mesh': 'D014150'}]"
+1075,24894748,A metoprolol-terbinafine combination induced bradycardia.,"To report a sinus bradycardia induced by metoprolol and terbinafine drug-drug interaction and its management. A 63 year-old Caucasian man on metoprolol 200 mg/day for stable coronary artery disease was prescribed a 90-day course of oral terbinafine 250 mg/day for onychomycosis. On the 49th day of terbinafine therapy, he was brought to the emergency room for a decrease of his global health status, confusion and falls. The electrocardiogram revealed a 37 beats/min sinus bradycardia. A score of 7 on the Naranjo adverse drug reaction probability scale indicates a probable relationship between the patient's sinus bradycardia and the drug interaction between metoprolol and terbinafine. The heart rate ameliorated first with a decrease in the dose of metoprolol. It was subsequently changed to bisoprolol and the heart rate remained normal. By inhibiting the cytochrome P450 2D6, terbinafine had decreased metoprolol's clearance, leading in metoprolol accumulation which has resulted in clinically significant sinus bradycardia.","[{'text': 'metoprolol', 'type': 'Chemical', 'start': 2, 'end': 12, 'mesh': 'D008790'}, {'text': 'terbinafine', 'type': 'Chemical', 'start': 13, 'end': 24, 'mesh': 'C041359'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 45, 'end': 56, 'mesh': 'D001919'}, {'text': 'sinus bradycardia', 'type': 'Disease', 'start': 70, 'end': 87, 'mesh': 'D012804'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 99, 'end': 109, 'mesh': 'D008790'}, {'text': 'terbinafine', 'type': 'Chemical', 'start': 114, 'end': 125, 'mesh': 'C041359'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 199, 'end': 209, 'mesh': 'D008790'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 232, 'end': 255, 'mesh': 'D003324'}, {'text': 'terbinafine', 'type': 'Chemical', 'start': 295, 'end': 306, 'mesh': 'C041359'}, {'text': 'onychomycosis', 'type': 'Disease', 'start': 322, 'end': 335, 'mesh': 'D014009'}, {'text': 'terbinafine', 'type': 'Chemical', 'start': 356, 'end': 367, 'mesh': 'C041359'}, {'text': 'confusion', 'type': 'Disease', 'start': 458, 'end': 467, 'mesh': 'D003221'}, {'text': 'sinus bradycardia', 'type': 'Disease', 'start': 525, 'end': 542, 'mesh': 'D012804'}, {'text': 'adverse drug reaction', 'type': 'Disease', 'start': 572, 'end': 593, 'mesh': 'D064420'}, {'text': 'sinus bradycardia', 'type': 'Disease', 'start': 668, 'end': 685, 'mesh': 'D012804'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 719, 'end': 729, 'mesh': 'D008790'}, {'text': 'terbinafine', 'type': 'Chemical', 'start': 734, 'end': 745, 'mesh': 'C041359'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 811, 'end': 821, 'mesh': 'D008790'}, {'text': 'bisoprolol', 'type': 'Chemical', 'start': 854, 'end': 864, 'mesh': 'D017298'}, {'text': 'terbinafine', 'type': 'Chemical', 'start': 940, 'end': 951, 'mesh': 'C041359'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 966, 'end': 976, 'mesh': 'D008790'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 1001, 'end': 1011, 'mesh': 'D008790'}, {'text': 'sinus bradycardia', 'type': 'Disease', 'start': 1070, 'end': 1087, 'mesh': 'D012804'}]"
+1076,24897009,Optochiasmatic and peripheral neuropathy due to ethambutol overtreatment.,"Ethambutol is known to cause optic neuropathy and, more rarely, axonal polyneuropathy. We characterize the clinical, neurophysiological, and neuroimaging findings in a 72-year-old man who developed visual loss and paresthesias after 11 weeks of exposure to a supratherapeutic dose of ethambutol. This case demonstrates the selective vulnerability of the anterior visual pathways and peripheral nerves to ethambutol toxicity.","[{'text': 'peripheral neuropathy', 'type': 'Disease', 'start': 19, 'end': 40, 'mesh': 'D010523'}, {'text': 'ethambutol', 'type': 'Chemical', 'start': 48, 'end': 58, 'mesh': 'D004977'}, {'text': 'Ethambutol', 'type': 'Chemical', 'start': 74, 'end': 84, 'mesh': 'D004977'}, {'text': 'optic neuropathy', 'type': 'Disease', 'start': 103, 'end': 119, 'mesh': 'D009901'}, {'text': 'polyneuropathy', 'type': 'Disease', 'start': 145, 'end': 159, 'mesh': 'D011115'}, {'text': 'visual loss', 'type': 'Disease', 'start': 272, 'end': 283, 'mesh': 'D014786'}, {'text': 'paresthesias', 'type': 'Disease', 'start': 288, 'end': 300, 'mesh': 'D010292'}, {'text': 'ethambutol', 'type': 'Chemical', 'start': 358, 'end': 368, 'mesh': 'D004977'}, {'text': 'ethambutol', 'type': 'Chemical', 'start': 478, 'end': 488, 'mesh': 'D004977'}, {'text': 'toxicity', 'type': 'Disease', 'start': 489, 'end': 497, 'mesh': 'D064420'}]"
+1077,24902786,Testosterone ameliorates streptozotocin-induced memory impairment in male rats.,"AIM: To study the effects of testosterone on streptozotocin (STZ)-induced memory impairment in male rats. METHODS: Adult male Wistar rats were intracerebroventricularly (icv) infused with STZ (750 ug) on d 1 and d 3, and a passive avoidance task was assessed 2 weeks after the first injection of STZ. Castration surgery was performed in another group of rats, and the passive avoidance task was assessed 4 weeks after the operation. Testosterone (1 mg.kg(-1).d(-1), sc), the androgen receptor antagonist flutamide (10 mg.kg(-1).d(-1), ip), the estrogen receptor antagonist tamoxifen (1 mg.kg(-1).d(-1), ip) or the aromatase inhibitor letrozole (4 mg.kg(-1).d(-1), ip) were administered for 6 d after the first injection of STZ. RESULTS: STZ administration and castration markedly decreased both STL1 (the short memory) and STL2 (the long memory) in passive avoidance tests. Testosterone replacement almost restored the STL1 and STL2 in castrated rats, and significantly prolonged the STL1 and STL2 in STZ-treated rats. Administration of flutamide, letrozole or tamoxifen significantly impaired the memory in intact rats, and significantly attenuated the testosterone replacement in improving STZ- and castration-induced memory impairment. CONCLUSION: Testosterone administration ameliorates STZ- and castration-induced memory impairment in male Wistar rats.","[{'text': 'Testosterone', 'type': 'Chemical', 'start': 0, 'end': 12, 'mesh': 'D013739'}, {'text': 'streptozotocin', 'type': 'Chemical', 'start': 25, 'end': 39, 'mesh': 'D013311'}, {'text': 'memory impairment', 'type': 'Disease', 'start': 48, 'end': 65, 'mesh': 'D008569'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 109, 'end': 121, 'mesh': 'D013739'}, {'text': 'streptozotocin', 'type': 'Chemical', 'start': 125, 'end': 139, 'mesh': 'D013311'}, {'text': 'STZ', 'type': 'Chemical', 'start': 141, 'end': 144, 'mesh': 'D013311'}, {'text': 'memory impairment', 'type': 'Disease', 'start': 154, 'end': 171, 'mesh': 'D008569'}, {'text': 'STZ', 'type': 'Chemical', 'start': 268, 'end': 271, 'mesh': 'D013311'}, {'text': 'STZ', 'type': 'Chemical', 'start': 376, 'end': 379, 'mesh': 'D013311'}, {'text': 'Testosterone', 'type': 'Chemical', 'start': 513, 'end': 525, 'mesh': 'D013739'}, {'text': 'androgen', 'type': 'Chemical', 'start': 555, 'end': 563, 'mesh': 'D000728'}, {'text': 'flutamide', 'type': 'Chemical', 'start': 584, 'end': 593, 'mesh': 'D005485'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 624, 'end': 632, 'mesh': 'D004967'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 653, 'end': 662, 'mesh': 'D013629'}, {'text': 'letrozole', 'type': 'Chemical', 'start': 714, 'end': 723, 'mesh': 'C067431'}, {'text': 'STZ', 'type': 'Chemical', 'start': 803, 'end': 806, 'mesh': 'D013311'}, {'text': 'STZ', 'type': 'Chemical', 'start': 817, 'end': 820, 'mesh': 'D013311'}, {'text': 'Testosterone', 'type': 'Chemical', 'start': 954, 'end': 966, 'mesh': 'D013739'}, {'text': 'STZ', 'type': 'Chemical', 'start': 1081, 'end': 1084, 'mesh': 'D013311'}, {'text': 'flutamide', 'type': 'Chemical', 'start': 1117, 'end': 1126, 'mesh': 'D005485'}, {'text': 'letrozole', 'type': 'Chemical', 'start': 1128, 'end': 1137, 'mesh': 'C067431'}, {'text': 'tamoxifen', 'type': 'Chemical', 'start': 1141, 'end': 1150, 'mesh': 'D013629'}, {'text': 'impaired the memory', 'type': 'Disease', 'start': 1165, 'end': 1184, 'mesh': 'D008569'}, {'text': 'testosterone', 'type': 'Chemical', 'start': 1234, 'end': 1246, 'mesh': 'D013739'}, {'text': 'STZ', 'type': 'Chemical', 'start': 1272, 'end': 1275, 'mesh': 'D013311'}, {'text': 'memory impairment', 'type': 'Disease', 'start': 1300, 'end': 1317, 'mesh': 'D008569'}, {'text': 'Testosterone', 'type': 'Chemical', 'start': 1331, 'end': 1343, 'mesh': 'D013739'}, {'text': 'STZ', 'type': 'Chemical', 'start': 1371, 'end': 1374, 'mesh': 'D013311'}, {'text': 'memory impairment', 'type': 'Disease', 'start': 1399, 'end': 1416, 'mesh': 'D008569'}]"
+1078,24911645,Behavioral and neurochemical studies in mice pretreated with garcinielliptone FC in pilocarpine-induced seizures.,"Garcinielliptone FC (GFC) isolated from hexanic fraction seed extract of species Platonia insignis Mart. It is widely used in folk medicine to treat skin diseases in both humans and animals as well as the seed decoction has been used to treat diarrheas and inflammatory diseases. However, there is no research on GFC effects in the central nervous system of rodents. The present study aimed to evaluate the GFC effects at doses of 25, 50 or 75 mg/kg on seizure parameters to determine their anticonvulsant activity and its effects on amino acid (r-aminobutyric acid (GABA), glutamine, aspartate and glutathione) levels as well as on acetylcholinesterase (AChE) activity in mice hippocampus after seizures. GFC produced an increased latency to first seizure, at doses 25mg/kg (20.12 + 2.20 min), 50mg/kg (20.95 + 2.21 min) or 75 mg/kg (23.43 + 1.99 min) when compared with seized mice. In addition, GABA content of mice hippocampus treated with GFC75 plus P400 showed an increase of 46.90% when compared with seized mice. In aspartate, glutamine and glutamate levels detected a decrease of 5.21%, 13.55% and 21.80%, respectively in mice hippocampus treated with GFC75 plus P400 when compared with seized mice. Hippocampus mice treated with GFC75 plus P400 showed an increase in AChE activity (63.30%) when compared with seized mice. The results indicate that GFC can exert anticonvulsant activity and reduce the frequency of installation of pilocarpine-induced status epilepticus, as demonstrated by increase in latency to first seizure and decrease in mortality rate of animals. In conclusion, our data suggest that GFC may influence in epileptogenesis and promote anticonvulsant actions in pilocarpine model by modulating the GABA and glutamate contents and of AChE activity in seized mice hippocampus. This compound may be useful to produce neuronal protection and it can be considered as an anticonvulsant agent.","[{'text': 'garcinielliptone FC', 'type': 'Chemical', 'start': 61, 'end': 80, 'mesh': 'C573355'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 84, 'end': 95, 'mesh': 'D010862'}, {'text': 'seizures', 'type': 'Disease', 'start': 104, 'end': 112, 'mesh': 'D012640'}, {'text': 'Garcinielliptone FC', 'type': 'Chemical', 'start': 114, 'end': 133, 'mesh': 'C573355'}, {'text': 'GFC', 'type': 'Chemical', 'start': 135, 'end': 138, 'mesh': 'C573355'}, {'text': 'skin diseases', 'type': 'Disease', 'start': 263, 'end': 276, 'mesh': 'D012871'}, {'text': 'diarrheas', 'type': 'Disease', 'start': 357, 'end': 366, 'mesh': 'D003967'}, {'text': 'inflammatory diseases', 'type': 'Disease', 'start': 371, 'end': 392, 'mesh': 'D007249'}, {'text': 'GFC', 'type': 'Chemical', 'start': 427, 'end': 430, 'mesh': 'C573355'}, {'text': 'GFC', 'type': 'Chemical', 'start': 521, 'end': 524, 'mesh': 'C573355'}, {'text': 'seizure', 'type': 'Disease', 'start': 567, 'end': 574, 'mesh': 'D012640'}, {'text': 'amino acid', 'type': 'Chemical', 'start': 648, 'end': 658, 'mesh': 'D000596'}, {'text': 'r-aminobutyric acid', 'type': 'Chemical', 'start': 660, 'end': 679, 'mesh': 'D005680'}, {'text': 'GABA', 'type': 'Chemical', 'start': 681, 'end': 685, 'mesh': 'D005680'}, {'text': 'glutamine', 'type': 'Chemical', 'start': 688, 'end': 697, 'mesh': 'D018698'}, {'text': 'aspartate', 'type': 'Chemical', 'start': 699, 'end': 708, 'mesh': 'D001224'}, {'text': 'glutathione', 'type': 'Chemical', 'start': 713, 'end': 724, 'mesh': 'D005978'}, {'text': 'seizures', 'type': 'Disease', 'start': 810, 'end': 818, 'mesh': 'D012640'}, {'text': 'GFC', 'type': 'Chemical', 'start': 820, 'end': 823, 'mesh': 'C573355'}, {'text': 'seizure', 'type': 'Disease', 'start': 863, 'end': 870, 'mesh': 'D012640'}, {'text': 'GABA', 'type': 'Chemical', 'start': 1012, 'end': 1016, 'mesh': 'D005680'}, {'text': 'aspartate', 'type': 'Chemical', 'start': 1138, 'end': 1147, 'mesh': 'D001224'}, {'text': 'glutamine', 'type': 'Chemical', 'start': 1149, 'end': 1158, 'mesh': 'D018698'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 1163, 'end': 1172, 'mesh': 'D018698'}, {'text': 'GFC', 'type': 'Chemical', 'start': 1472, 'end': 1475, 'mesh': 'C573355'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1554, 'end': 1565, 'mesh': 'D010862'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 1574, 'end': 1592, 'mesh': 'D013226'}, {'text': 'seizure', 'type': 'Disease', 'start': 1642, 'end': 1649, 'mesh': 'D012640'}, {'text': 'GFC', 'type': 'Chemical', 'start': 1730, 'end': 1733, 'mesh': 'C573355'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1805, 'end': 1816, 'mesh': 'D010862'}, {'text': 'GABA', 'type': 'Chemical', 'start': 1841, 'end': 1845, 'mesh': 'D005680'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 1850, 'end': 1859, 'mesh': 'D018698'}]"
+1079,24923469,"Standard operating procedures for antibiotic therapy and the occurrence of acute kidney injury: a prospective, clinical, non-interventional, observational study.","INTRODUCTION: Acute kidney injury (AKI) occurs in 7% of hospitalized and 66% of Intensive Care Unit (ICU) patients. It increases mortality, hospital length of stay, and costs. The aim of this study was to investigate, whether there is an association between adherence to guidelines (standard operating procedures (SOP)) for potentially nephrotoxic antibiotics and the occurrence of AKI. METHODS: This study was carried out as a prospective, clinical, non-interventional, observational study. Data collection was performed over a total of 170 days in three ICUs at Charite - Universitaetsmedizin Berlin. A total of 675 patients were included; 163 of these had therapy with vancomycin, gentamicin, or tobramycin; were >18 years; and treated in the ICU for >24 hours. Patients with an adherence to SOP >70% were classified into the high adherence group (HAG) and patients with an adherence of <70% into the low adherence group (LAG). AKI was defined according to RIFLE criteria. Adherence to SOPs was evaluated by retrospective expert audit. Development of AKI was compared between groups with exact Chi2-test and multivariate logistic regression analysis (two-sided P <0.05). RESULTS: LAG consisted of 75 patients (46%) versus 88 HAG patients (54%). AKI occurred significantly more often in LAG with 36% versus 21% in HAG (P = 0.035). Basic characteristics were comparable, except an increased rate of soft tissue infections in LAG. Multivariate analysis revealed an odds ratio of 2.5-fold for LAG to develop AKI compared with HAG (95% confidence interval 1.195 to 5.124, P = 0.039). CONCLUSION: Low adherence to SOPs for potentially nephrotoxic antibiotics was associated with a higher occurrence of AKI. TRIAL REGISTRATION: Current Controlled Trials ISRCTN54598675. Registered 17 August 2007.","[{'text': 'acute kidney injury', 'type': 'Disease', 'start': 75, 'end': 94, 'mesh': 'D058186'}, {'text': 'Acute kidney injury', 'type': 'Disease', 'start': 176, 'end': 195, 'mesh': 'D058186'}, {'text': 'AKI', 'type': 'Disease', 'start': 197, 'end': 200, 'mesh': 'D058186'}, {'text': 'nephrotoxic', 'type': 'Disease', 'start': 498, 'end': 509, 'mesh': 'D007674'}, {'text': 'AKI', 'type': 'Disease', 'start': 544, 'end': 547, 'mesh': 'D058186'}, {'text': 'vancomycin', 'type': 'Chemical', 'start': 834, 'end': 844, 'mesh': 'D014640'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 846, 'end': 856, 'mesh': 'D005839'}, {'text': 'tobramycin', 'type': 'Chemical', 'start': 861, 'end': 871, 'mesh': 'D014031'}, {'text': 'AKI', 'type': 'Disease', 'start': 1093, 'end': 1096, 'mesh': 'D058186'}, {'text': 'AKI', 'type': 'Disease', 'start': 1216, 'end': 1219, 'mesh': 'D058186'}, {'text': 'AKI', 'type': 'Disease', 'start': 1410, 'end': 1413, 'mesh': 'D058186'}, {'text': 'infections', 'type': 'Disease', 'start': 1574, 'end': 1584, 'mesh': 'D007239'}, {'text': 'AKI', 'type': 'Disease', 'start': 1669, 'end': 1672, 'mesh': 'D058186'}, {'text': 'nephrotoxic', 'type': 'Disease', 'start': 1794, 'end': 1805, 'mesh': 'D007674'}, {'text': 'AKI', 'type': 'Disease', 'start': 1861, 'end': 1864, 'mesh': 'D058186'}]"
+1080,24927617,Rhabdomyolysis in a hepatitis C virus infected patient treated with telaprevir and simvastatin.,"A 46-year old man with a chronic hepatitis C virus infection received triple therapy with ribavirin, pegylated interferon and telaprevir. The patient also received simvastatin. One month after starting the antiviral therapy, the patient was admitted to the hospital because he developed rhabdomyolysis. At admission simvastatin and all antiviral drugs were discontinued because toxicity due to a drug-drug interaction was suspected. The creatine kinase peaked at 62,246 IU/L and the patient was treated with intravenous normal saline. The patient's renal function remained unaffected. Fourteen days after hospitalization, creatine kinase level had returned to 230 IU/L and the patient was discharged. Telaprevir was considered the probable causative agent of an interaction with simvastatin according to the Drug Interaction Probability Scale. The interaction is due to inhibition of CYP3A4-mediated simvastatin clearance. Simvastatin plasma concentration increased 30 times in this patient and statin induced muscle toxicity is related to the concentration of the statin in blood. In conclusion, with this case we illustrate that telaprevir as well as statins are susceptible to clinical relevant drug-drug interactions.","[{'text': 'Rhabdomyolysis', 'type': 'Disease', 'start': 0, 'end': 14, 'mesh': 'D012206'}, {'text': 'hepatitis C virus infected', 'type': 'Disease', 'start': 20, 'end': 46, 'mesh': 'D006526'}, {'text': 'telaprevir', 'type': 'Chemical', 'start': 68, 'end': 78, 'mesh': 'C486464'}, {'text': 'simvastatin', 'type': 'Chemical', 'start': 83, 'end': 94, 'mesh': 'D019821'}, {'text': 'hepatitis C virus infection', 'type': 'Disease', 'start': 129, 'end': 156, 'mesh': 'D006526'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 186, 'end': 195, 'mesh': 'D012254'}, {'text': 'pegylated interferon', 'type': 'Chemical', 'start': 197, 'end': 217, 'mesh': 'C417083'}, {'text': 'telaprevir', 'type': 'Chemical', 'start': 222, 'end': 232, 'mesh': 'C486464'}, {'text': 'simvastatin', 'type': 'Chemical', 'start': 260, 'end': 271, 'mesh': 'D019821'}, {'text': 'rhabdomyolysis', 'type': 'Disease', 'start': 383, 'end': 397, 'mesh': 'D012206'}, {'text': 'simvastatin', 'type': 'Chemical', 'start': 412, 'end': 423, 'mesh': 'D019821'}, {'text': 'toxicity', 'type': 'Disease', 'start': 474, 'end': 482, 'mesh': 'D064420'}, {'text': 'creatine', 'type': 'Chemical', 'start': 533, 'end': 541, 'mesh': 'D003401'}, {'text': 'creatine', 'type': 'Chemical', 'start': 718, 'end': 726, 'mesh': 'D003401'}, {'text': 'Telaprevir', 'type': 'Chemical', 'start': 797, 'end': 807, 'mesh': 'C486464'}, {'text': 'simvastatin', 'type': 'Chemical', 'start': 875, 'end': 886, 'mesh': 'D019821'}, {'text': 'simvastatin', 'type': 'Chemical', 'start': 996, 'end': 1007, 'mesh': 'D019821'}, {'text': 'Simvastatin', 'type': 'Chemical', 'start': 1019, 'end': 1030, 'mesh': 'D019821'}, {'text': 'statin', 'type': 'Chemical', 'start': 1091, 'end': 1097, 'mesh': 'D019821'}, {'text': 'muscle toxicity', 'type': 'Disease', 'start': 1106, 'end': 1121, 'mesh': 'D009135'}, {'text': 'statin', 'type': 'Chemical', 'start': 1161, 'end': 1167, 'mesh': 'D019821'}, {'text': 'telaprevir', 'type': 'Chemical', 'start': 1227, 'end': 1237, 'mesh': 'C486464'}, {'text': 'statins', 'type': 'Chemical', 'start': 1249, 'end': 1256, 'mesh': 'D019821'}]"
+1081,24928523,"Combination of bortezomib, thalidomide, and dexamethasone (VTD) as a consolidation therapy after autologous stem cell transplantation for symptomatic multiple myeloma in Japanese patients.","Consolidation therapy for patients with multiple myeloma (MM) has been widely adopted to improve treatment response following autologous stem cell transplantation. In this study, we retrospectively analyzed the safety and efficacy of combination regimen of bortezomib, thalidomide, and dexamethasone (VTD) as consolidation therapy in 24 Japanese patients with newly diagnosed MM. VTD consisted of bortezomib at a dose of 1.3 mg/m(2) and dexamethasone at a dose of 40 mg/day on days 1, 8, 15, and 22 of a 35-day cycle, with daily oral thalidomide at a dose of 100 mg/day. Grade 3-4 neutropenia and thrombocytopenia were documented in four and three patients (17 and 13 %), respectively, but drug dose reduction due to cytopenia was not required in any case. Peripheral neuropathy was common (63 %), but severe grade 3-4 peripheral neuropathy was not observed. Very good partial response or better response (>VGPR) rates before and after consolidation therapy were 54 and 79 %, respectively. Patients had a significant probability of improving from <VGPR before consolidation therapy to >VGPR after consolidation therapy (p = 0.041). The VTD regimen may be safe and effective as a consolidation therapy in the treatment of MM in Japanese population.","[{'text': 'bortezomib', 'type': 'Chemical', 'start': 15, 'end': 25, 'mesh': 'C400082'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 27, 'end': 38, 'mesh': 'D013792'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 44, 'end': 57, 'mesh': 'D003907'}, {'text': 'multiple myeloma', 'type': 'Disease', 'start': 150, 'end': 166, 'mesh': 'D009101'}, {'text': 'multiple myeloma', 'type': 'Disease', 'start': 229, 'end': 245, 'mesh': 'D009101'}, {'text': 'MM', 'type': 'Disease', 'start': 247, 'end': 249, 'mesh': 'D009101'}, {'text': 'bortezomib', 'type': 'Chemical', 'start': 446, 'end': 456, 'mesh': 'C400082'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 458, 'end': 469, 'mesh': 'D013792'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 475, 'end': 488, 'mesh': 'D003907'}, {'text': 'MM', 'type': 'Disease', 'start': 565, 'end': 567, 'mesh': 'D009101'}, {'text': 'bortezomib', 'type': 'Chemical', 'start': 586, 'end': 596, 'mesh': 'C400082'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 626, 'end': 639, 'mesh': 'D003907'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 723, 'end': 734, 'mesh': 'D013792'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 770, 'end': 781, 'mesh': 'D009503'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 786, 'end': 802, 'mesh': 'D013921'}, {'text': 'cytopenia', 'type': 'Disease', 'start': 906, 'end': 915, 'mesh': 'D006402'}, {'text': 'Peripheral neuropathy', 'type': 'Disease', 'start': 946, 'end': 967, 'mesh': 'D010523'}, {'text': 'peripheral neuropathy', 'type': 'Disease', 'start': 1008, 'end': 1029, 'mesh': 'D010523'}]"
+1082,24971338,"Conversion to sirolimus ameliorates cyclosporine-induced nephropathy in the rat: focus on serum, urine, gene, and protein renal expression biomarkers.","Protocols of conversion from cyclosporin A (CsA) to sirolimus (SRL) have been widely used in immunotherapy after transplantation to prevent CsA-induced nephropathy, but the molecular mechanisms underlying these protocols remain nuclear. This study aimed to identify the molecular pathways and putative biomarkers of CsA-to-SRL conversion in a rat model. Four animal groups (n = 6) were tested during 9 weeks: control, CsA, SRL, and conversion (CsA for 3 weeks followed by SRL for 6 weeks). Classical and emergent serum, urinary, and kidney tissue (gene and protein expression) markers were assessed. Renal lesions were analyzed in hematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome stains. SRL-treated rats presented proteinuria and NGAL (serum and urinary) as the best markers of renal impairment. Short CsA treatment presented slight or even absent kidney lesions and TGF-b, NF- kb, mTOR, PCNA, TP53, KIM-1, and CTGF as relevant gene and protein changes. Prolonged CsA exposure aggravated renal damage, without clear changes on the traditional markers, but with changes in serums TGF- b and IL-7, TBARs clearance, and kidney TGF-b and mTOR. Conversion to SRL prevented CsA-induced renal damage evolution (absent/mild grade lesions), while NGAL (serum versus urine) seems to be a feasible biomarker of CsA replacement to SRL.","[{'text': 'sirolimus', 'type': 'Chemical', 'start': 14, 'end': 23, 'mesh': 'D020123'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 36, 'end': 48, 'mesh': 'D016572'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 57, 'end': 68, 'mesh': 'D007674'}, {'text': 'cyclosporin A', 'type': 'Chemical', 'start': 180, 'end': 193, 'mesh': 'D016572'}, {'text': 'CsA', 'type': 'Chemical', 'start': 195, 'end': 198, 'mesh': 'D016572'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 203, 'end': 212, 'mesh': 'D020123'}, {'text': 'SRL', 'type': 'Chemical', 'start': 214, 'end': 217, 'mesh': 'D020123'}, {'text': 'CsA', 'type': 'Chemical', 'start': 291, 'end': 294, 'mesh': 'D016572'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 303, 'end': 314, 'mesh': 'D007674'}, {'text': 'CsA', 'type': 'Chemical', 'start': 467, 'end': 470, 'mesh': 'D016572'}, {'text': 'SRL', 'type': 'Chemical', 'start': 474, 'end': 477, 'mesh': 'D020123'}, {'text': 'CsA', 'type': 'Chemical', 'start': 569, 'end': 572, 'mesh': 'D016572'}, {'text': 'SRL', 'type': 'Chemical', 'start': 574, 'end': 577, 'mesh': 'D020123'}, {'text': 'CsA', 'type': 'Chemical', 'start': 595, 'end': 598, 'mesh': 'D016572'}, {'text': 'SRL', 'type': 'Chemical', 'start': 623, 'end': 626, 'mesh': 'D020123'}, {'text': 'Renal lesions', 'type': 'Disease', 'start': 751, 'end': 764, 'mesh': 'D007674'}, {'text': 'hematoxylin', 'type': 'Chemical', 'start': 782, 'end': 793, 'mesh': 'D006416'}, {'text': 'eosin', 'type': 'Chemical', 'start': 798, 'end': 803, 'mesh': 'D004801'}, {'text': 'SRL', 'type': 'Chemical', 'start': 858, 'end': 861, 'mesh': 'D020123'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 885, 'end': 896, 'mesh': 'D011507'}, {'text': 'renal impairment', 'type': 'Disease', 'start': 949, 'end': 965, 'mesh': 'D007674'}, {'text': 'CsA', 'type': 'Chemical', 'start': 973, 'end': 976, 'mesh': 'D016572'}, {'text': 'kidney lesions', 'type': 'Disease', 'start': 1019, 'end': 1033, 'mesh': 'D007674'}, {'text': 'CsA', 'type': 'Chemical', 'start': 1135, 'end': 1138, 'mesh': 'D016572'}, {'text': 'renal damage', 'type': 'Disease', 'start': 1159, 'end': 1171, 'mesh': 'D007674'}, {'text': 'SRL', 'type': 'Chemical', 'start': 1325, 'end': 1328, 'mesh': 'D020123'}, {'text': 'CsA', 'type': 'Chemical', 'start': 1339, 'end': 1342, 'mesh': 'D016572'}, {'text': 'renal damage', 'type': 'Disease', 'start': 1351, 'end': 1363, 'mesh': 'D007674'}, {'text': 'CsA', 'type': 'Chemical', 'start': 1471, 'end': 1474, 'mesh': 'D016572'}, {'text': 'SRL', 'type': 'Chemical', 'start': 1490, 'end': 1493, 'mesh': 'D020123'}]"
+1083,24975837,Kinin B2 receptor deletion and blockage ameliorates cisplatin-induced acute renal injury.,"Cisplatin treatment has been adopted in some chemotherapies; however, this drug can induce acute kidney injury due its ability to negatively affect renal function, augment serum levels of creatinine and urea, increase the acute tubular necrosis score and up-regulate cytokines (e.g., IL-1b and TNF-a). The kinin B2 receptor has been associated with the inflammation process, as well as the regulation of cytokine expression, and its deletion resulted in an improvement in the diabetic nephropathy status. To examine the role of the kinin B2 receptor in cisplatin-induced acute kidney injury, kinin B2 receptor knockout mice were challenged with cisplatin. Additionally, WT mice were treated with a B2 receptor antagonist after cisplatin administration. B2 receptor-deficient mice were less sensitive to this drug than the WT mice, as shown by reduced weight loss, better preservation of kidney function, down regulation of inflammatory cytokines and less acute tubular necrosis. Moreover, treatment with the kinin B2 receptor antagonist effectively reduced the levels of serum creatinine and blood urea after cisplatin administration. Thus, our data suggest that the kinin B2 receptor is involved in cisplatin-induced acute kidney injury by mediating the necrotic process and the expression of inflammatory cytokines, thus resulting in declined renal function. These results highlight the kinin B2 receptor antagonist treatment in amelioration of nephrotoxicity induced by cisplatin therapy.","[{'text': 'cisplatin', 'type': 'Chemical', 'start': 52, 'end': 61, 'mesh': 'D002945'}, {'text': 'acute renal injury', 'type': 'Disease', 'start': 70, 'end': 88, 'mesh': 'D058186'}, {'text': 'Cisplatin', 'type': 'Chemical', 'start': 90, 'end': 99, 'mesh': 'D002945'}, {'text': 'acute kidney injury', 'type': 'Disease', 'start': 181, 'end': 200, 'mesh': 'D058186'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 278, 'end': 288, 'mesh': 'D003404'}, {'text': 'urea', 'type': 'Chemical', 'start': 293, 'end': 297, 'mesh': 'D014508'}, {'text': 'acute tubular necrosis', 'type': 'Disease', 'start': 312, 'end': 334, 'mesh': 'D007683'}, {'text': 'inflammation', 'type': 'Disease', 'start': 443, 'end': 455, 'mesh': 'D007249'}, {'text': 'diabetic nephropathy', 'type': 'Disease', 'start': 566, 'end': 586, 'mesh': 'D003928'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 643, 'end': 652, 'mesh': 'D002945'}, {'text': 'acute kidney injury', 'type': 'Disease', 'start': 661, 'end': 680, 'mesh': 'D058186'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 735, 'end': 744, 'mesh': 'D002945'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 817, 'end': 826, 'mesh': 'D002945'}, {'text': 'weight loss', 'type': 'Disease', 'start': 941, 'end': 952, 'mesh': 'D015431'}, {'text': 'acute tubular necrosis', 'type': 'Disease', 'start': 1045, 'end': 1067, 'mesh': 'D007683'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1167, 'end': 1177, 'mesh': 'D003404'}, {'text': 'urea', 'type': 'Chemical', 'start': 1188, 'end': 1192, 'mesh': 'D014508'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 1199, 'end': 1208, 'mesh': 'D002945'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 1290, 'end': 1299, 'mesh': 'D002945'}, {'text': 'acute kidney injury', 'type': 'Disease', 'start': 1308, 'end': 1327, 'mesh': 'D058186'}, {'text': 'necrotic', 'type': 'Disease', 'start': 1345, 'end': 1353, 'mesh': 'D009336'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1537, 'end': 1551, 'mesh': 'D007674'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 1563, 'end': 1572, 'mesh': 'D002945'}]"
+1084,24999722,Safety and efficacy of fluocinolone acetonide intravitreal implant (0.59 mg) in birdshot retinochoroidopathy.,"PURPOSE: To report the treatment outcomes of the fluocinolone acetonide intravitreal implant (0.59 mg) in patients with birdshot retinochoroidopathy whose disease is refractory or intolerant to conventional immunomodulatory therapy. METHODS: A retrospective case series involving 11 birdshot retinochoroidopathy patients (11 eyes). Eleven patients (11 eyes) underwent surgery for fluocinolone acetonide implant (0.59 mg). Treatment outcomes of interest were noted at baseline, before fluocinolone acetonide implant, and then at 6 months, 1 year, 2 years, 3 years, and beyond 3 years. Disease activity markers, including signs of ocular inflammation, evidence of retinal vasculitis, Swedish interactive threshold algorithm-short wavelength automated perimetry Humphrey visual field analysis, electroretinographic parameters, and optical coherence tomography were recorded. Data on occurrence of cataract and raised intraocular pressure were collected in all eyes. RESULTS: Intraocular inflammation was present in 54.5, 9.9, 11.1, and 0% of patients at baseline, 6 months, 1 year, 2 years, 3 years, and beyond 3 years after receiving the implant, respectively. Active vasculitis was noted in 36.3% patients at baseline and 0% at 3 years of follow-up. More than 20% (47.61-67.2%) reduction in central retinal thickness was noted in all patients with cystoid macular edema at 6 months, 1 year, 2 years, and 3 years postimplant. At baseline, 54.5% patients were on immunomodulatory agents. This percentage decreased to 45.45, 44.4, and 14.28% at 1 year, 2 years, and 3 years postimplant, respectively. Adverse events included increased intraocular pressure (54.5%) and cataract formation (100%). CONCLUSION: The data suggest that fluocinolone acetonide implant (0.59 mg) helps to control inflammation in otherwise treatment-refractory cases of birdshot retinochoroidopathy. It is associated with significant side effects of cataract and ocular hypertension requiring treatment.","[{'text': 'fluocinolone acetonide', 'type': 'Chemical', 'start': 23, 'end': 45, 'mesh': 'D005446'}, {'text': 'birdshot retinochoroidopathy', 'type': 'Disease', 'start': 80, 'end': 108, 'mesh': 'C537630'}, {'text': 'fluocinolone acetonide', 'type': 'Chemical', 'start': 159, 'end': 181, 'mesh': 'D005446'}, {'text': 'birdshot retinochoroidopathy', 'type': 'Disease', 'start': 230, 'end': 258, 'mesh': 'C537630'}, {'text': 'birdshot retinochoroidopathy', 'type': 'Disease', 'start': 393, 'end': 421, 'mesh': 'C537630'}, {'text': 'fluocinolone acetonide', 'type': 'Chemical', 'start': 490, 'end': 512, 'mesh': 'D005446'}, {'text': 'fluocinolone acetonide', 'type': 'Chemical', 'start': 594, 'end': 616, 'mesh': 'D005446'}, {'text': 'inflammation', 'type': 'Disease', 'start': 746, 'end': 758, 'mesh': 'D007249'}, {'text': 'retinal vasculitis', 'type': 'Disease', 'start': 772, 'end': 790, 'mesh': 'D031300'}, {'text': 'cataract', 'type': 'Disease', 'start': 1004, 'end': 1012, 'mesh': 'D002386'}, {'text': 'raised intraocular pressure', 'type': 'Disease', 'start': 1017, 'end': 1044, 'mesh': 'D009798'}, {'text': 'inflammation', 'type': 'Disease', 'start': 1094, 'end': 1106, 'mesh': 'D007249'}, {'text': 'vasculitis', 'type': 'Disease', 'start': 1276, 'end': 1286, 'mesh': 'D014657'}, {'text': 'cystoid macular edema', 'type': 'Disease', 'start': 1457, 'end': 1478, 'mesh': 'D008269'}, {'text': 'increased intraocular pressure', 'type': 'Disease', 'start': 1731, 'end': 1761, 'mesh': 'D009798'}, {'text': 'cataract', 'type': 'Disease', 'start': 1774, 'end': 1782, 'mesh': 'D002386'}, {'text': 'fluocinolone acetonide', 'type': 'Chemical', 'start': 1835, 'end': 1857, 'mesh': 'D005446'}, {'text': 'inflammation', 'type': 'Disease', 'start': 1893, 'end': 1905, 'mesh': 'D007249'}, {'text': 'birdshot retinochoroidopathy', 'type': 'Disease', 'start': 1949, 'end': 1977, 'mesh': 'C537630'}, {'text': 'cataract', 'type': 'Disease', 'start': 2029, 'end': 2037, 'mesh': 'D002386'}, {'text': 'ocular hypertension', 'type': 'Disease', 'start': 2042, 'end': 2061, 'mesh': 'D009798'}]"
+1085,25006369,Optimal precurarizing dose of rocuronium to decrease fasciculation and myalgia following succinylcholine administration.,"BACKGROUND: Succinylcholine commonly produces frequent adverse effects, including muscle fasciculation and myalgia. The current study identified the optimal dose of rocuronium to prevent succinylcholine-induced fasciculation and myalgia and evaluated the influence of rocuronium on the speed of onset produced by succinylcholine. METHODS: This randomized, double-blinded study was conducted in 100 patients randomly allocated into five groups of 20 patients each. Patients were randomized to receive 0.02, 0.03, 0.04, 0.05 and 0.06 mg/kg rocuronium as a precurarizing dose. Neuromuscular monitoring after each precurarizing dose was recorded from the adductor pollicis muscle using acceleromyography with train-of-four stimulation of the ulnar nerve. All patients received succinylcholine 1.5 mg/kg at 2 minutes after the precurarization, and were assessed the incidence and severity of fasciculations, while myalgia was assessed at 24 hours after surgery. RESULTS: The incidence and severity of visible muscle fasciculation was significantly less with increasing the amount of precurarizing dose of rocuronium (P < 0.001). Those of myalgia tend to decrease according to increasing the amount of precurarizing dose of rocuronium, but there was no significance (P = 0.072). The onset time of succinylcholine was significantly longer with increasing the amount of precurarizing dose of rocuronium (P < 0.001). CONCLUSIONS: Precurarization with 0.04 mg/kg rocuronium was the optimal dose considering the reduction in the incidence and severity of fasciculation and myalgia with acceptable onset time, and the safe and effective precurarization.","[{'text': 'rocuronium', 'type': 'Chemical', 'start': 30, 'end': 40, 'mesh': 'C061870'}, {'text': 'fasciculation', 'type': 'Disease', 'start': 53, 'end': 66, 'mesh': 'D005207'}, {'text': 'myalgia', 'type': 'Disease', 'start': 71, 'end': 78, 'mesh': 'D063806'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 89, 'end': 104, 'mesh': 'D013390'}, {'text': 'Succinylcholine', 'type': 'Chemical', 'start': 133, 'end': 148, 'mesh': 'D013390'}, {'text': 'muscle fasciculation', 'type': 'Disease', 'start': 203, 'end': 223, 'mesh': 'D005207'}, {'text': 'myalgia', 'type': 'Disease', 'start': 228, 'end': 235, 'mesh': 'D063806'}, {'text': 'rocuronium', 'type': 'Chemical', 'start': 286, 'end': 296, 'mesh': 'C061870'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 308, 'end': 323, 'mesh': 'D013390'}, {'text': 'fasciculation', 'type': 'Disease', 'start': 332, 'end': 345, 'mesh': 'D005207'}, {'text': 'myalgia', 'type': 'Disease', 'start': 350, 'end': 357, 'mesh': 'D063806'}, {'text': 'rocuronium', 'type': 'Chemical', 'start': 389, 'end': 399, 'mesh': 'C061870'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 434, 'end': 449, 'mesh': 'D013390'}, {'text': 'rocuronium', 'type': 'Chemical', 'start': 659, 'end': 669, 'mesh': 'C061870'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 894, 'end': 909, 'mesh': 'D013390'}, {'text': 'fasciculations', 'type': 'Disease', 'start': 1008, 'end': 1022, 'mesh': 'D005207'}, {'text': 'myalgia', 'type': 'Disease', 'start': 1030, 'end': 1037, 'mesh': 'D063806'}, {'text': 'muscle fasciculation', 'type': 'Disease', 'start': 1125, 'end': 1145, 'mesh': 'D005207'}, {'text': 'rocuronium', 'type': 'Chemical', 'start': 1221, 'end': 1231, 'mesh': 'C061870'}, {'text': 'myalgia', 'type': 'Disease', 'start': 1254, 'end': 1261, 'mesh': 'D063806'}, {'text': 'rocuronium', 'type': 'Chemical', 'start': 1339, 'end': 1349, 'mesh': 'C061870'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 1412, 'end': 1427, 'mesh': 'D013390'}, {'text': 'rocuronium', 'type': 'Chemical', 'start': 1505, 'end': 1515, 'mesh': 'C061870'}, {'text': 'rocuronium', 'type': 'Chemical', 'start': 1574, 'end': 1584, 'mesh': 'C061870'}, {'text': 'fasciculation', 'type': 'Disease', 'start': 1665, 'end': 1678, 'mesh': 'D005207'}, {'text': 'myalgia', 'type': 'Disease', 'start': 1683, 'end': 1690, 'mesh': 'D063806'}]"
+1086,25006961,Absence of PKC-alpha attenuates lithium-induced nephrogenic diabetes insipidus.,"Lithium, an effective antipsychotic, induces nephrogenic diabetes insipidus (NDI) in  40% of patients. The decreased capacity to concentrate urine is likely due to lithium acutely disrupting the cAMP pathway and chronically reducing urea transporter (UT-A1) and water channel (AQP2) expression in the inner medulla. Targeting an alternative signaling pathway, such as PKC-mediated signaling, may be an effective method of treating lithium-induced polyuria. PKC-alpha null mice (PKCa KO) and strain-matched wild type (WT) controls were treated with lithium for 0, 3 or 5 days. WT mice had increased urine output and lowered urine osmolality after 3 and 5 days of treatment whereas PKCa KO mice had no change in urine output or concentration. Western blot analysis revealed that AQP2 expression in medullary tissues was lowered after 3 and 5 days in WT mice; however, AQP2 was unchanged in PKCa KO. Similar results were observed with UT-A1 expression. Animals were also treated with lithium for 6 weeks. Lithium-treated WT mice had 19-fold increased urine output whereas treated PKCa KO animals had a 4-fold increase in output. AQP2 and UT-A1 expression was lowered in 6 week lithium-treated WT animals whereas in treated PKCa KO mice, AQP2 was only reduced by 2-fold and UT-A1 expression was unaffected. Urinary sodium, potassium and calcium were elevated in lithium-fed WT but not in lithium-fed PKCa KO mice. Our data show that ablation of PKCa preserves AQP2 and UT-A1 protein expression and localization in lithium-induced NDI, and prevents the development of the severe polyuria associated with lithium therapy.","[{'text': 'lithium', 'type': 'Chemical', 'start': 32, 'end': 39, 'mesh': 'D008094'}, {'text': 'nephrogenic diabetes insipidus', 'type': 'Disease', 'start': 48, 'end': 78, 'mesh': 'D018500'}, {'text': 'Lithium', 'type': 'Chemical', 'start': 80, 'end': 87, 'mesh': 'D008094'}, {'text': 'nephrogenic diabetes insipidus', 'type': 'Disease', 'start': 125, 'end': 155, 'mesh': 'D018500'}, {'text': 'NDI', 'type': 'Disease', 'start': 157, 'end': 160, 'mesh': 'D018500'}, {'text': 'lithium', 'type': 'Chemical', 'start': 244, 'end': 251, 'mesh': 'D008094'}, {'text': 'cAMP', 'type': 'Chemical', 'start': 275, 'end': 279, 'mesh': 'D000242'}, {'text': 'urea', 'type': 'Chemical', 'start': 313, 'end': 317, 'mesh': 'D014508'}, {'text': 'lithium', 'type': 'Chemical', 'start': 511, 'end': 518, 'mesh': 'D008094'}, {'text': 'polyuria', 'type': 'Disease', 'start': 527, 'end': 535, 'mesh': 'D011141'}, {'text': 'lithium', 'type': 'Chemical', 'start': 628, 'end': 635, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1061, 'end': 1068, 'mesh': 'D008094'}, {'text': 'Lithium', 'type': 'Chemical', 'start': 1082, 'end': 1089, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1254, 'end': 1261, 'mesh': 'D008094'}, {'text': 'sodium', 'type': 'Chemical', 'start': 1391, 'end': 1397, 'mesh': 'D012964'}, {'text': 'potassium', 'type': 'Chemical', 'start': 1399, 'end': 1408, 'mesh': 'D011188'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1413, 'end': 1420, 'mesh': 'D002118'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1438, 'end': 1445, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1464, 'end': 1471, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1590, 'end': 1597, 'mesh': 'D008094'}, {'text': 'NDI', 'type': 'Disease', 'start': 1606, 'end': 1609, 'mesh': 'D018500'}, {'text': 'polyuria', 'type': 'Disease', 'start': 1654, 'end': 1662, 'mesh': 'D011141'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1679, 'end': 1686, 'mesh': 'D008094'}]"
+1087,25031906,Is Dysguesia Going to be a Rare or a Common Side-effect of Amlodipine?,"A very rare side-effect of amlodipine is dysguesia. A review of the literature produced only one case. We report a case about a female with essential hypertension on drug treatment with amlodipine developed loss of taste sensation. Condition moderately improved on stoppage of the drug for 25 days. We conclude that amlodipine can cause dysguesia. Here, we describe the clinical presentation and review the relevant literature on amlodipine and dysguesia.","[{'text': 'Dysguesia', 'type': 'Disease', 'start': 3, 'end': 12, 'mesh': 'D004408'}, {'text': 'Amlodipine', 'type': 'Chemical', 'start': 59, 'end': 69, 'mesh': 'D017311'}, {'text': 'amlodipine', 'type': 'Chemical', 'start': 98, 'end': 108, 'mesh': 'D017311'}, {'text': 'dysguesia', 'type': 'Disease', 'start': 112, 'end': 121, 'mesh': 'D004408'}, {'text': 'hypertension', 'type': 'Disease', 'start': 221, 'end': 233, 'mesh': 'D006973'}, {'text': 'amlodipine', 'type': 'Chemical', 'start': 257, 'end': 267, 'mesh': 'D017311'}, {'text': 'loss of taste sensation', 'type': 'Disease', 'start': 278, 'end': 301, 'mesh': 'D012678'}, {'text': 'amlodipine', 'type': 'Chemical', 'start': 387, 'end': 397, 'mesh': 'D017311'}, {'text': 'dysguesia', 'type': 'Disease', 'start': 408, 'end': 417, 'mesh': 'D004408'}, {'text': 'amlodipine', 'type': 'Chemical', 'start': 501, 'end': 511, 'mesh': 'D017311'}, {'text': 'dysguesia', 'type': 'Disease', 'start': 516, 'end': 525, 'mesh': 'D004408'}]"
+1088,25041770,Rhabdomyolysis in association with simvastatin and dosage increment in clarithromycin.,"Clarithromycin is the most documented cytochrome P450 3A4 (CYP3A4) inhibitor to cause an adverse interaction with simvastatin. This particular case is of interest as rhabdomyolysis only occurred after an increase in the dose of clarithromycin. The patient developed raised cardiac biomarkers without any obvious cardiac issues, a phenomenon that has been linked to rhabdomyolysis previously. To date, there has been no reported effect of rhabdomyolysis on the structure and function of cardiac muscle. Clinicians need to be aware of prescribing concomitant medications that increase the risk of myopathy or inhibit the CYP3A4 enzyme. Our case suggests that troponin elevation could be associated with statin induced rhabdomyolysis, which may warrant further studies.","[{'text': 'Rhabdomyolysis', 'type': 'Disease', 'start': 0, 'end': 14, 'mesh': 'D012206'}, {'text': 'simvastatin', 'type': 'Chemical', 'start': 35, 'end': 46, 'mesh': 'D019821'}, {'text': 'clarithromycin', 'type': 'Chemical', 'start': 71, 'end': 85, 'mesh': 'D017291'}, {'text': 'Clarithromycin', 'type': 'Chemical', 'start': 87, 'end': 101, 'mesh': 'D017291'}, {'text': 'simvastatin', 'type': 'Chemical', 'start': 201, 'end': 212, 'mesh': 'D019821'}, {'text': 'rhabdomyolysis', 'type': 'Disease', 'start': 253, 'end': 267, 'mesh': 'D012206'}, {'text': 'clarithromycin', 'type': 'Chemical', 'start': 315, 'end': 329, 'mesh': 'D017291'}, {'text': 'rhabdomyolysis', 'type': 'Disease', 'start': 452, 'end': 466, 'mesh': 'D012206'}, {'text': 'rhabdomyolysis', 'type': 'Disease', 'start': 525, 'end': 539, 'mesh': 'D012206'}, {'text': 'myopathy', 'type': 'Disease', 'start': 682, 'end': 690, 'mesh': 'D009135'}, {'text': 'statin', 'type': 'Chemical', 'start': 788, 'end': 794, 'mesh': 'D019821'}, {'text': 'rhabdomyolysis', 'type': 'Disease', 'start': 803, 'end': 817, 'mesh': 'D012206'}]"
+1089,25054547,"Characterization of a novel BCHE ""silent"" allele: point mutation (p.Val204Asp) causes loss of activity and prolonged apnea with suxamethonium.","Butyrylcholinesterase deficiency is characterized by prolonged apnea after the use of muscle relaxants (suxamethonium or mivacurium) in patients who have mutations in the BCHE gene. Here, we report a case of prolonged neuromuscular block after administration of suxamethonium leading to the discovery of a novel BCHE variant (c.695T>A, p.Val204Asp). Inhibition studies, kinetic analysis and molecular dynamics were undertaken to understand how this mutation disrupts the catalytic triad and determines a ""silent"" phenotype. Low activity of patient plasma butyrylcholinesterase with butyrylthiocholine (BTC) and benzoylcholine, and values of dibucaine and fluoride numbers fit with heterozygous atypical silent genotype. Electrophoretic analysis of plasma BChE of the proband and his mother showed that patient has a reduced amount of tetrameric enzyme in plasma and that minor fast-moving BChE components: monomer, dimer, and monomer-albumin conjugate are missing. Kinetic analysis showed that the p.Val204Asp/p.Asp70Gly-p.Ala539Thr BChE displays a pure Michaelian behavior with BTC as the substrate. Both catalytic parameters Km = 265 uM for BTC, two times higher than that of the atypical enzyme, and a low Vmax are consistent with the absence of activity against suxamethonium. Molecular dynamic (MD) simulations showed that the overall effect of the mutation p.Val204Asp is disruption of hydrogen bonding between Gln223 and Glu441, leading Ser198 and His438 to move away from each other with subsequent disruption of the catalytic triad functionality regardless of the type of substrate. MD also showed that the enzyme volume is increased, suggesting a pre-denaturation state. This fits with the reduced concentration of p.Ala204Asp/p.Asp70Gly-p.Ala539Thr tetrameric enzyme in the plasma and non-detectable fast moving-bands on electrophoresis gels.","[{'text': 'apnea', 'type': 'Disease', 'start': 117, 'end': 122, 'mesh': 'D001049'}, {'text': 'suxamethonium', 'type': 'Chemical', 'start': 128, 'end': 141, 'mesh': 'D013390'}, {'text': 'Butyrylcholinesterase deficiency', 'type': 'Disease', 'start': 143, 'end': 175, 'mesh': 'C537417'}, {'text': 'apnea', 'type': 'Disease', 'start': 206, 'end': 211, 'mesh': 'D001049'}, {'text': 'suxamethonium', 'type': 'Chemical', 'start': 247, 'end': 260, 'mesh': 'D013390'}, {'text': 'mivacurium', 'type': 'Chemical', 'start': 264, 'end': 274, 'mesh': 'C049430'}, {'text': 'suxamethonium', 'type': 'Chemical', 'start': 405, 'end': 418, 'mesh': 'D013390'}, {'text': 'butyrylthiocholine', 'type': 'Chemical', 'start': 725, 'end': 743, 'mesh': 'D002092'}, {'text': 'BTC', 'type': 'Chemical', 'start': 745, 'end': 748, 'mesh': 'D002092'}, {'text': 'benzoylcholine', 'type': 'Chemical', 'start': 754, 'end': 768, 'mesh': 'D001588'}, {'text': 'dibucaine', 'type': 'Chemical', 'start': 784, 'end': 793, 'mesh': 'D003992'}, {'text': 'fluoride', 'type': 'Chemical', 'start': 798, 'end': 806, 'mesh': 'D005459'}, {'text': 'BTC', 'type': 'Chemical', 'start': 1222, 'end': 1225, 'mesh': 'D002092'}, {'text': 'BTC', 'type': 'Chemical', 'start': 1286, 'end': 1289, 'mesh': 'D002092'}, {'text': 'suxamethonium', 'type': 'Chemical', 'start': 1409, 'end': 1422, 'mesh': 'D013390'}, {'text': 'hydrogen', 'type': 'Chemical', 'start': 1535, 'end': 1543, 'mesh': 'D006859'}]"
+1090,25071004,Delayed anemia after treatment with injectable artesunate in the Democratic Republic of the Congo: a manageable issue.,"Cases of delayed hemolytic anemia have been described after treatment with injectable artesunate, the current World Health Organization (WHO)-recommended first-line drug for the treatment of severe malaria. A total of 350 patients (215 [61.4%] < 5 years of age and 135 [38.6%] > 5 years of age) were followed-up after treatment with injectable artesunate for severe malaria in hospitals and health centers of the Democratic Republic of the Congo. Complete series of hemoglobin (Hb) measurements were available for 201 patients. A decrease in Hb levels between 2 and 5 g/dL was detected in 23 (11.4%) patients during the follow-up period. For five patients, Hb levels decreased below 5 g/dL during at least one follow-up visit. All cases of delayed anemia were clinically manageable and resolved within one month.","[{'text': 'anemia', 'type': 'Disease', 'start': 8, 'end': 14, 'mesh': 'D000740'}, {'text': 'artesunate', 'type': 'Chemical', 'start': 47, 'end': 57, 'mesh': 'C039726'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 136, 'end': 152, 'mesh': 'D000743'}, {'text': 'artesunate', 'type': 'Chemical', 'start': 205, 'end': 215, 'mesh': 'C039726'}, {'text': 'malaria', 'type': 'Disease', 'start': 317, 'end': 324, 'mesh': 'D008288'}, {'text': 'artesunate', 'type': 'Chemical', 'start': 463, 'end': 473, 'mesh': 'C039726'}, {'text': 'malaria', 'type': 'Disease', 'start': 485, 'end': 492, 'mesh': 'D008288'}, {'text': 'anemia', 'type': 'Disease', 'start': 867, 'end': 873, 'mesh': 'D000740'}]"
+1091,25080425,Regulation of signal transducer and activator of transcription 3 and apoptotic pathways by betaine attenuates isoproterenol-induced acute myocardial injury in rats.,"The present study was designed to investigate the cardioprotective effects of betaine on acute myocardial ischemia induced experimentally in rats focusing on regulation of signal transducer and activator of transcription 3 (STAT3) and apoptotic pathways as the potential mechanism underlying the drug effect. Male Sprague Dawley rats were treated with betaine (100, 200, and 400 mg/kg) orally for 40 days. Acute myocardial ischemic injury was induced in rats by subcutaneous injection of isoproterenol (85 mg/kg), for two consecutive days. Serum cardiac marker enzyme, histopathological variables and expression of protein levels were analyzed. Oral administration of betaine (200 and 400 mg/kg) significantly reduced the level of cardiac marker enzyme in the serum and prevented left ventricular remodeling. Western blot analysis showed that isoproterenol-induced phosphorylation of STAT3 was maintained or further enhanced by betaine treatment in myocardium. Furthermore, betaine (200 and 400 mg/kg) treatment increased the ventricular expression of Bcl-2 and reduced the level of Bax, therefore causing a significant increase in the ratio of Bcl-2/Bax. The protective role of betaine on myocardial damage was further confirmed by histopathological examination. In summary, our results showed that betaine pretreatment attenuated isoproterenol-induced acute myocardial ischemia via the regulation of STAT3 and apoptotic pathways.","[{'text': 'betaine', 'type': 'Chemical', 'start': 91, 'end': 98, 'mesh': 'D001622'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 110, 'end': 123, 'mesh': 'D007545'}, {'text': 'myocardial injury', 'type': 'Disease', 'start': 138, 'end': 155, 'mesh': 'D009202'}, {'text': 'betaine', 'type': 'Chemical', 'start': 243, 'end': 250, 'mesh': 'D001622'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 260, 'end': 279, 'mesh': 'D017202'}, {'text': 'betaine', 'type': 'Chemical', 'start': 517, 'end': 524, 'mesh': 'D001622'}, {'text': 'myocardial ischemic injury', 'type': 'Disease', 'start': 577, 'end': 603, 'mesh': 'D017202'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 653, 'end': 666, 'mesh': 'D007545'}, {'text': 'betaine', 'type': 'Chemical', 'start': 833, 'end': 840, 'mesh': 'D001622'}, {'text': 'ventricular remodeling', 'type': 'Disease', 'start': 950, 'end': 972, 'mesh': 'D020257'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1008, 'end': 1021, 'mesh': 'D007545'}, {'text': 'betaine', 'type': 'Chemical', 'start': 1093, 'end': 1100, 'mesh': 'D001622'}, {'text': 'betaine', 'type': 'Chemical', 'start': 1139, 'end': 1146, 'mesh': 'D001622'}, {'text': 'betaine', 'type': 'Chemical', 'start': 1344, 'end': 1351, 'mesh': 'D001622'}, {'text': 'myocardial damage', 'type': 'Disease', 'start': 1355, 'end': 1372, 'mesh': 'D009202'}, {'text': 'betaine', 'type': 'Chemical', 'start': 1465, 'end': 1472, 'mesh': 'D001622'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1497, 'end': 1510, 'mesh': 'D007545'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 1525, 'end': 1544, 'mesh': 'D017202'}]"
+1092,25084821,Quetiapine-induced neutropenia in a bipolar patient with hepatocellular carcinoma.,"OBJECTIVE: Quetiapine is a dibenzothiazepine derivative, similar to clozapine, which has the highest risk of causing blood dyscrasias, especially neutropenia. There are some case reports about this side effect of quetiapine, but possible risk factors are seldom discussed and identified. A case of a patient with hepatocellular carcinoma that developed neutropenia after treatment with quetiapine is described here. CASE REPORT: A 62-year-old Taiwanese widow with bipolar disorder was diagnosed with hepatocellular carcinoma at age 60. She developed leucopenia after being treated with quetiapine. After quetiapine was discontinued, her white blood cell count returned to normal. CONCLUSIONS: Although neutropenia is not a common side effect of quetiapine, physicians should be cautious about its presentation and associated risk factors. Hepatic dysfunction may be one of the possible risk factors, and concomitant fever may be a diagnostic marker for adverse reaction to quetiapine.","[{'text': 'Quetiapine', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'C069541'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 19, 'end': 30, 'mesh': 'D009503'}, {'text': 'bipolar', 'type': 'Disease', 'start': 36, 'end': 43, 'mesh': 'D001714'}, {'text': 'hepatocellular carcinoma', 'type': 'Disease', 'start': 57, 'end': 81, 'mesh': 'D006528'}, {'text': 'Quetiapine', 'type': 'Chemical', 'start': 94, 'end': 104, 'mesh': 'C069541'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 151, 'end': 160, 'mesh': 'D003024'}, {'text': 'blood dyscrasias', 'type': 'Disease', 'start': 200, 'end': 216, 'mesh': 'D006402'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 229, 'end': 240, 'mesh': 'D009503'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 296, 'end': 306, 'mesh': 'C069541'}, {'text': 'hepatocellular carcinoma', 'type': 'Disease', 'start': 396, 'end': 420, 'mesh': 'D006528'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 436, 'end': 447, 'mesh': 'D009503'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 469, 'end': 479, 'mesh': 'C069541'}, {'text': 'bipolar disorder', 'type': 'Disease', 'start': 547, 'end': 563, 'mesh': 'D001714'}, {'text': 'hepatocellular carcinoma', 'type': 'Disease', 'start': 583, 'end': 607, 'mesh': 'D006528'}, {'text': 'leucopenia', 'type': 'Disease', 'start': 633, 'end': 643, 'mesh': 'D007970'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 669, 'end': 679, 'mesh': 'C069541'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 687, 'end': 697, 'mesh': 'C069541'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 785, 'end': 796, 'mesh': 'D009503'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 828, 'end': 838, 'mesh': 'C069541'}, {'text': 'Hepatic dysfunction', 'type': 'Disease', 'start': 922, 'end': 941, 'mesh': 'D008107'}, {'text': 'fever', 'type': 'Disease', 'start': 999, 'end': 1004, 'mesh': 'D005334'}, {'text': 'quetiapine', 'type': 'Chemical', 'start': 1056, 'end': 1066, 'mesh': 'C069541'}]"
+1093,25096313,Lateral antebrachial cutaneous neuropathy after steroid injection at lateral epicondyle.,"BACKGROUND AND OBJECTIVES: This report aimed to present a case of lateral antebrachial cutaneous neuropathy (LACNP) that occurred after a steroid injection in the lateral epicondyle to treat lateral epicondylitis in a 40-year-old woman. MATERIAL AND METHOD: A 40-year-old woman presented with decreased sensation and paresthesia over her right lateral forearm; the paresthesia had occurred after a steroid injection in the right lateral epicondyle 3 months before. Her sensation of light touch and pain was diminished over the lateral side of the right forearm and wrist area. RESULTS: The sensory action potential amplitude of the right lateral antebrachial cutaneous nerve (LACN) (6.2 uV) was lower than that of the left (13.1 uV). The difference of amplitude between both sides was significant because there was more than a 50% reduction. She was diagnosed with right LACNP (mainly axonal involvement) on the basis of the clinical manifestation and the electrodiagnostic findings. Her symptoms improved through physical therapy but persisted to some degree. CONCLUSION: This report describes the case of a woman with LACNP that developed after a steroid injection for the treatment of lateral epicondylitis. An electrodiagnostic study, including a nerve conduction study of the LACN, was helpful to diagnose right LACNP and to find the passage of the LACN on the lateral epicondyle.","[{'text': 'neuropathy', 'type': 'Disease', 'start': 31, 'end': 41, 'mesh': 'D009422'}, {'text': 'steroid', 'type': 'Chemical', 'start': 48, 'end': 55, 'mesh': 'D013256'}, {'text': 'neuropathy', 'type': 'Disease', 'start': 186, 'end': 196, 'mesh': 'D009422'}, {'text': 'steroid', 'type': 'Chemical', 'start': 227, 'end': 234, 'mesh': 'D013256'}, {'text': 'lateral epicondylitis', 'type': 'Disease', 'start': 280, 'end': 301, 'mesh': 'D013716'}, {'text': 'paresthesia', 'type': 'Disease', 'start': 406, 'end': 417, 'mesh': 'D010292'}, {'text': 'paresthesia', 'type': 'Disease', 'start': 454, 'end': 465, 'mesh': 'D010292'}, {'text': 'steroid', 'type': 'Chemical', 'start': 487, 'end': 494, 'mesh': 'D013256'}, {'text': 'pain', 'type': 'Disease', 'start': 587, 'end': 591, 'mesh': 'D010146'}, {'text': 'steroid', 'type': 'Chemical', 'start': 1238, 'end': 1245, 'mesh': 'D013256'}, {'text': 'lateral epicondylitis', 'type': 'Disease', 'start': 1277, 'end': 1298, 'mesh': 'D013716'}]"
+1094,25119790,"Curcumin prevents maleate-induced nephrotoxicity: relation to hemodynamic alterations, oxidative stress, mitochondrial oxygen consumption and activity of respiratory complex I.","The potential protective effect of the dietary antioxidant curcumin (120 mg/Kg/day for 6 days) against the renal injury induced by maleate was evaluated. Tubular proteinuria and oxidative stress were induced by a single injection of maleate (400 mg/kg) in rats. Maleate-induced renal injury included increase in renal vascular resistance and in the urinary excretion of total protein, glucose, sodium, neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl b-D-glucosaminidase (NAG), upregulation of kidney injury molecule (KIM)-1, decrease in renal blood flow and claudin-2 expression besides of necrosis and apoptosis of tubular cells on 24 h. Oxidative stress was determined by measuring the oxidation of lipids and proteins and diminution in renal Nrf2 levels. Studies were also conducted in renal epithelial LLC-PK1 cells and in mitochondria isolated from kidneys of all the experimental groups. Maleate induced cell damage and reactive oxygen species (ROS) production in LLC-PK1 cells in culture. In addition, maleate treatment reduced oxygen consumption in ADP-stimulated mitochondria and diminished respiratory control index when using malate/glutamate as substrate. The activities of both complex I and aconitase were also diminished. All the above-described alterations were prevented by curcumin. It is concluded that curcumin is able to attenuate in vivo maleate-induced nephropathy and in vitro cell damage. The in vivo protection was associated to the prevention of oxidative stress and preservation of mitochondrial oxygen consumption and activity of respiratory complex I, and the in vitro protection was associated to the prevention of ROS production.","[{'text': 'Curcumin', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D003474'}, {'text': 'maleate', 'type': 'Chemical', 'start': 18, 'end': 25, 'mesh': 'C030272'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 34, 'end': 48, 'mesh': 'D007674'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 119, 'end': 125, 'mesh': 'D010100'}, {'text': 'curcumin', 'type': 'Chemical', 'start': 236, 'end': 244, 'mesh': 'D003474'}, {'text': 'renal injury', 'type': 'Disease', 'start': 284, 'end': 296, 'mesh': 'D007674'}, {'text': 'maleate', 'type': 'Chemical', 'start': 308, 'end': 315, 'mesh': 'C030272'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 339, 'end': 350, 'mesh': 'D011507'}, {'text': 'maleate', 'type': 'Chemical', 'start': 410, 'end': 417, 'mesh': 'C030272'}, {'text': 'Maleate', 'type': 'Chemical', 'start': 439, 'end': 446, 'mesh': 'C030272'}, {'text': 'renal injury', 'type': 'Disease', 'start': 455, 'end': 467, 'mesh': 'D007674'}, {'text': 'glucose', 'type': 'Chemical', 'start': 562, 'end': 569, 'mesh': 'D005947'}, {'text': 'sodium', 'type': 'Chemical', 'start': 571, 'end': 577, 'mesh': 'D012964'}, {'text': 'kidney injury', 'type': 'Disease', 'start': 685, 'end': 698, 'mesh': 'D007674'}, {'text': 'necrosis', 'type': 'Disease', 'start': 782, 'end': 790, 'mesh': 'D009336'}, {'text': 'Maleate', 'type': 'Chemical', 'start': 1086, 'end': 1093, 'mesh': 'C030272'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 1127, 'end': 1133, 'mesh': 'D010100'}, {'text': 'maleate', 'type': 'Chemical', 'start': 1201, 'end': 1208, 'mesh': 'C030272'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 1227, 'end': 1233, 'mesh': 'D010100'}, {'text': 'ADP', 'type': 'Chemical', 'start': 1249, 'end': 1252, 'mesh': 'D000244'}, {'text': 'malate', 'type': 'Chemical', 'start': 1329, 'end': 1335, 'mesh': 'C030298'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 1336, 'end': 1345, 'mesh': 'D018698'}, {'text': 'curcumin', 'type': 'Chemical', 'start': 1483, 'end': 1491, 'mesh': 'D003474'}, {'text': 'curcumin', 'type': 'Chemical', 'start': 1514, 'end': 1522, 'mesh': 'D003474'}, {'text': 'maleate', 'type': 'Chemical', 'start': 1552, 'end': 1559, 'mesh': 'C030272'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1568, 'end': 1579, 'mesh': 'D007674'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 1716, 'end': 1722, 'mesh': 'D010100'}]"
+1095,25907210,Incidence of solid tumours among pesticide applicators exposed to the organophosphate insecticide diazinon in the Agricultural Health Study: an updated analysis.,"OBJECTIVE: Diazinon, a common organophosphate insecticide with genotoxic properties, was previously associated with lung cancer in the Agricultural Health Study (AHS) cohort, but few other epidemiological studies have examined diazinon-associated cancer risk. We used updated diazinon exposure and cancer incidence information to evaluate solid tumour risk in the AHS. METHODS: Male pesticide applicators in Iowa and North Carolina reported lifetime diazinon use at enrolment (1993-1997) and follow-up (1998-2005); cancer incidence was assessed through 2010(North Carolina)/2011(Iowa). Among applicators with usage information sufficient to evaluate exposure-response patterns, we used Poisson regression to estimate adjusted rate ratios (RRs) and 95% CI for cancer sites with >10 exposed cases for both lifetime (LT) exposure days and intensity-weighted (IW) lifetime exposure days (accounting for factors impacting exposure). RESULTS: We observed elevated lung cancer risks (N=283) among applicators with the greatest number of LT (RR=1.60; 95% CI 1.11 to 2.31; Ptrend=0.02) and IW days of diazinon use (RR=1.41; 95% CI 0.98 to 2.04; Ptrend=0.08). Kidney cancer (N=94) risks were non-significantly elevated (RRLT days=1.77; 95% CI 0.90 to 3.51; Ptrend=0.09; RRIW days 1.37; 95% CI 0.64 to 2.92; Ptrend=0.50), as were risks for aggressive prostate cancer (N=656). CONCLUSIONS: Our updated evaluation of diazinon provides additional evidence of an association with lung cancer risk. Newly identified links to kidney cancer and associations with aggressive prostate cancer require further evaluation.","[{'text': 'tumours', 'type': 'Disease', 'start': 19, 'end': 26, 'mesh': 'D009369'}, {'text': 'organophosphate', 'type': 'Chemical', 'start': 70, 'end': 85, 'mesh': 'D010755'}, {'text': 'diazinon', 'type': 'Chemical', 'start': 98, 'end': 106, 'mesh': 'D003976'}, {'text': 'Diazinon', 'type': 'Chemical', 'start': 173, 'end': 181, 'mesh': 'D003976'}, {'text': 'organophosphate', 'type': 'Chemical', 'start': 192, 'end': 207, 'mesh': 'D010755'}, {'text': 'lung cancer', 'type': 'Disease', 'start': 278, 'end': 289, 'mesh': 'D008175'}, {'text': 'diazinon', 'type': 'Chemical', 'start': 389, 'end': 397, 'mesh': 'D003976'}, {'text': 'cancer', 'type': 'Disease', 'start': 409, 'end': 415, 'mesh': 'D009369'}, {'text': 'diazinon', 'type': 'Chemical', 'start': 438, 'end': 446, 'mesh': 'D003976'}, {'text': 'cancer', 'type': 'Disease', 'start': 460, 'end': 466, 'mesh': 'D009369'}, {'text': 'tumour', 'type': 'Disease', 'start': 507, 'end': 513, 'mesh': 'D009369'}, {'text': 'diazinon', 'type': 'Chemical', 'start': 612, 'end': 620, 'mesh': 'D003976'}, {'text': 'cancer', 'type': 'Disease', 'start': 677, 'end': 683, 'mesh': 'D009369'}, {'text': 'cancer', 'type': 'Disease', 'start': 921, 'end': 927, 'mesh': 'D009369'}, {'text': 'lung cancer', 'type': 'Disease', 'start': 1120, 'end': 1131, 'mesh': 'D008175'}, {'text': 'diazinon', 'type': 'Chemical', 'start': 1254, 'end': 1262, 'mesh': 'D003976'}, {'text': 'Kidney cancer', 'type': 'Disease', 'start': 1312, 'end': 1325, 'mesh': 'D007680'}, {'text': 'prostate cancer', 'type': 'Disease', 'start': 1502, 'end': 1517, 'mesh': 'D011471'}, {'text': 'diazinon', 'type': 'Chemical', 'start': 1566, 'end': 1574, 'mesh': 'D003976'}, {'text': 'lung cancer', 'type': 'Disease', 'start': 1627, 'end': 1638, 'mesh': 'D008175'}, {'text': 'kidney cancer', 'type': 'Disease', 'start': 1671, 'end': 1684, 'mesh': 'D007680'}, {'text': 'prostate cancer', 'type': 'Disease', 'start': 1718, 'end': 1733, 'mesh': 'D011471'}]"
+1096,25951420,Associations of Ozone and PM2.5 Concentrations With Parkinson's Disease Among Participants in the Agricultural Health Study.,"OBJECTIVE: This study describes associations of ozone and fine particulate matter with Parkinson's disease observed among farmers in North Carolina and Iowa. METHODS: We used logistic regression to determine the associations of these pollutants with self-reported, doctor-diagnosed Parkinson's disease. Daily predicted pollutant concentrations were used to derive surrogates of long-term exposure and link them to study participants' geocoded addresses. RESULTS: We observed positive associations of Parkinson's disease with ozone (odds ratio = 1.39; 95% CI: 0.98 to 1.98) and fine particulate matter (odds ratio = 1.34; 95% CI: 0.93 to 1.93) in North Carolina but not in Iowa. CONCLUSIONS: The plausibility of an effect of ambient concentrations of these pollutants on Parkinson's disease risk is supported by experimental data demonstrating damage to dopaminergic neurons at relevant concentrations. Additional studies are needed to address uncertainties related to confounding and to examine temporal aspects of the associations we observed.","[{'text': 'Ozone', 'type': 'Chemical', 'start': 16, 'end': 21, 'mesh': 'D010126'}, {'text': ""Parkinson's Disease"", 'type': 'Disease', 'start': 52, 'end': 71, 'mesh': 'D010300'}, {'text': 'ozone', 'type': 'Chemical', 'start': 173, 'end': 178, 'mesh': 'D010126'}, {'text': 'particulate matter', 'type': 'Chemical', 'start': 188, 'end': 206, 'mesh': 'D052638'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 212, 'end': 231, 'mesh': 'D010300'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 407, 'end': 426, 'mesh': 'D010300'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 625, 'end': 644, 'mesh': 'D010300'}, {'text': 'ozone', 'type': 'Chemical', 'start': 650, 'end': 655, 'mesh': 'D010126'}, {'text': 'particulate matter', 'type': 'Chemical', 'start': 707, 'end': 725, 'mesh': 'D052638'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 895, 'end': 914, 'mesh': 'D010300'}]"
+1097,25986755,Low functional programming of renal AT2R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure.,"UNASSIGNED: Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT2R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT1aR)/AT2R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT2R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT2R might mediate the developmental origin of adult glomerulosclerosis.","[{'text': 'glomerulosclerosis', 'type': 'Disease', 'start': 78, 'end': 96, 'mesh': 'D005921'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 136, 'end': 144, 'mesh': 'D002110'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 214, 'end': 222, 'mesh': 'D002110'}, {'text': 'intrauterine growth retardation', 'type': 'Disease', 'start': 251, 'end': 282, 'mesh': 'D005317'}, {'text': 'IUGR', 'type': 'Disease', 'start': 284, 'end': 288, 'mesh': 'D005317'}, {'text': 'IUGR', 'type': 'Disease', 'start': 335, 'end': 339, 'mesh': 'D005317'}, {'text': 'glomerulosclerosis', 'type': 'Disease', 'start': 361, 'end': 379, 'mesh': 'D005921'}, {'text': 'glomerulosclerosis', 'type': 'Disease', 'start': 415, 'end': 433, 'mesh': 'D005921'}, {'text': 'glomerulosclerosis', 'type': 'Disease', 'start': 529, 'end': 547, 'mesh': 'D005921'}, {'text': 'IUGR', 'type': 'Disease', 'start': 634, 'end': 638, 'mesh': 'D005317'}, {'text': 'glomerulosclerosis', 'type': 'Disease', 'start': 826, 'end': 844, 'mesh': 'D005921'}, {'text': 'interstitial fibrosis', 'type': 'Disease', 'start': 856, 'end': 877, 'mesh': 'D005355'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 919, 'end': 929, 'mesh': 'D003404'}, {'text': 'angiotensin II', 'type': 'Chemical', 'start': 955, 'end': 969, 'mesh': 'D000804'}, {'text': 'angiotensin II', 'type': 'Chemical', 'start': 1066, 'end': 1080, 'mesh': 'D000804'}, {'text': 'tyrosine', 'type': 'Chemical', 'start': 1720, 'end': 1728, 'mesh': 'D014443'}, {'text': 'dysplasia of fetal kidneys', 'type': 'Disease', 'start': 1821, 'end': 1847, 'mesh': 'D007674'}, {'text': 'glomerulosclerosis', 'type': 'Disease', 'start': 1859, 'end': 1877, 'mesh': 'D005921'}, {'text': 'glomerulosclerosis', 'type': 'Disease', 'start': 1995, 'end': 2013, 'mesh': 'D005921'}]"
+1098,26002693,"1,3-Butadiene, CML and the t(9:22) translocation: A reality check.","UNASSIGNED: Epidemiological studies of 1,3-butadiene have suggest that exposures to humans are associated with chronic myeloid leukemia (CML). CML has a well-documented association with ionizing radiation, but reports of associations with chemical exposures have been questioned. Ionizing radiation is capable of inducing the requisite CML-associated t(9:22) translocation (Philadelphia chromosome) in appropriate cells in vitro but, thus far, chemicals have not shown this capacity. We have proposed that 1,3-butadiene metabolites be so tested as a reality check on the epidemiological reports. In order to conduct reliable testing in this regard, it is essential that a positive control for induction be available. We have used ionizing radiation to develop such a control. Results described here demonstrate that this agent does in fact induce pathogenic t(9:22) translocations in a human myeloid cell line in vitro, but does so at low frequencies. Conditions that will be required for studies of 1,3-butadiene are discussed.","[{'text': '1,3-Butadiene', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'C031763'}, {'text': 'CML', 'type': 'Disease', 'start': 15, 'end': 18, 'mesh': 'D015464'}, {'text': '1,3-butadiene', 'type': 'Chemical', 'start': 106, 'end': 119, 'mesh': 'C031763'}, {'text': 'chronic myeloid leukemia', 'type': 'Disease', 'start': 178, 'end': 202, 'mesh': 'D015464'}, {'text': 'CML', 'type': 'Disease', 'start': 204, 'end': 207, 'mesh': 'D015464'}, {'text': 'CML', 'type': 'Disease', 'start': 210, 'end': 213, 'mesh': 'D015464'}, {'text': 'CML', 'type': 'Disease', 'start': 403, 'end': 406, 'mesh': 'D015464'}, {'text': 'Philadelphia chromosome', 'type': 'Disease', 'start': 441, 'end': 464, 'mesh': 'D010677'}, {'text': '1,3-butadiene', 'type': 'Chemical', 'start': 573, 'end': 586, 'mesh': 'C031763'}, {'text': '1,3-butadiene', 'type': 'Chemical', 'start': 1067, 'end': 1080, 'mesh': 'C031763'}]"
+1099,26033014,Cancer incidence and metolachlor use in the Agricultural Health Study: An update.,"UNASSIGNED: Metolachlor, a widely used herbicide, is classified as a Group C carcinogen by the U.S. Environmental Protection Agency based on increased liver neoplasms in female rats. Epidemiologic studies of the health effects of metolachlor have been limited. The Agricultural Health Study (AHS) is a prospective cohort study including licensed private and commercial pesticide applicators in Iowa and North Carolina enrolled 1993-1997. We evaluated cancer incidence through 2010/2011 (NC/IA) for 49,616 applicators, 53% of whom reported ever using metolachlor. We used Poisson regression to evaluate relations between two metrics of metolachlor use (lifetime days, intensity-weighted lifetime days) and cancer incidence. We saw no association between metolachlor use and incidence of all cancers combined (n = 5,701 with a 5-year lag) or most site-specific cancers. For liver cancer, in analyses restricted to exposed workers, elevations observed at higher categories of use were not statistically significant. However, trends for both lifetime and intensity-weighted lifetime days of metolachor use were positive and statistically significant with an unexposed reference group. A similar pattern was observed for follicular cell lymphoma, but no other lymphoma subtypes. An earlier suggestion of increased lung cancer risk at high levels of metolachlor use in this cohort was not confirmed in this update. This suggestion of an association between metolachlor and liver cancer among pesticide applicators is a novel finding and echoes observation of increased liver neoplasms in some animal studies. However, our findings for both liver cancer and follicular cell lymphoma warrant follow-up to better differentiate effects of metolachlor use from other factors.","[{'text': 'Cancer', 'type': 'Disease', 'start': 0, 'end': 6, 'mesh': 'D009369'}, {'text': 'metolachlor', 'type': 'Chemical', 'start': 21, 'end': 32, 'mesh': 'C051786'}, {'text': 'Metolachlor', 'type': 'Chemical', 'start': 94, 'end': 105, 'mesh': 'C051786'}, {'text': 'liver neoplasms', 'type': 'Disease', 'start': 233, 'end': 248, 'mesh': 'D008113'}, {'text': 'metolachlor', 'type': 'Chemical', 'start': 312, 'end': 323, 'mesh': 'C051786'}, {'text': 'cancer', 'type': 'Disease', 'start': 533, 'end': 539, 'mesh': 'D009369'}, {'text': 'metolachlor', 'type': 'Chemical', 'start': 632, 'end': 643, 'mesh': 'C051786'}, {'text': 'metolachlor', 'type': 'Chemical', 'start': 717, 'end': 728, 'mesh': 'C051786'}, {'text': 'cancer', 'type': 'Disease', 'start': 787, 'end': 793, 'mesh': 'D009369'}, {'text': 'metolachlor', 'type': 'Chemical', 'start': 835, 'end': 846, 'mesh': 'C051786'}, {'text': 'cancers', 'type': 'Disease', 'start': 872, 'end': 879, 'mesh': 'D009369'}, {'text': 'cancers', 'type': 'Disease', 'start': 941, 'end': 948, 'mesh': 'D009369'}, {'text': 'liver cancer', 'type': 'Disease', 'start': 954, 'end': 966, 'mesh': 'D008113'}, {'text': 'metolachor', 'type': 'Chemical', 'start': 1169, 'end': 1179, 'mesh': 'C051786'}, {'text': 'follicular cell lymphoma', 'type': 'Disease', 'start': 1298, 'end': 1322, 'mesh': 'D008224'}, {'text': 'lymphoma', 'type': 'Disease', 'start': 1337, 'end': 1345, 'mesh': 'D008223'}, {'text': 'lung cancer', 'type': 'Disease', 'start': 1391, 'end': 1402, 'mesh': 'D008175'}, {'text': 'metolachlor', 'type': 'Chemical', 'start': 1426, 'end': 1437, 'mesh': 'C051786'}, {'text': 'metolachlor', 'type': 'Chemical', 'start': 1533, 'end': 1544, 'mesh': 'C051786'}, {'text': 'liver cancer', 'type': 'Disease', 'start': 1549, 'end': 1561, 'mesh': 'D008113'}, {'text': 'liver neoplasms', 'type': 'Disease', 'start': 1645, 'end': 1660, 'mesh': 'D008113'}, {'text': 'liver cancer', 'type': 'Disease', 'start': 1716, 'end': 1728, 'mesh': 'D008113'}, {'text': 'lymphoma', 'type': 'Disease', 'start': 1749, 'end': 1757, 'mesh': 'D008223'}, {'text': 'metolachlor', 'type': 'Chemical', 'start': 1811, 'end': 1822, 'mesh': 'C051786'}]"
+1100,26115410,Mechanisms Underlying Latent Disease Risk Associated with Early-Life Arsenic Exposure: Current Research Trends and Scientific Gaps.,"BACKGROUND: Millions of individuals worldwide, particularly those living in rural and developing areas, are exposed to harmful levels of inorganic arsenic (iAs) in their drinking water. Inorganic As exposure during key developmental periods is associated with a variety of adverse health effects including those that are evident in adulthood. There is considerable interest in identifying the molecular mechanisms that relate early-life iAs exposure to the development of these latent diseases, particularly in relationship to cancer. OBJECTIVES: This work summarizes research on the molecular mechanisms that underlie the increased risk of cancer development in adulthood that is associated with early-life iAs exposure. DISCUSSION: Epigenetic reprogramming that imparts functional changes in gene expression, the development of cancer stem cells, and immunomodulation are plausible underlying mechanisms by which early-life iAs exposure elicits latent carcinogenic effects. CONCLUSIONS: Evidence is mounting that relates early-life iAs exposure and cancer development later in life. Future research should include animal studies that address mechanistic hypotheses and studies of human populations that integrate early-life exposure, molecular alterations, and latent disease outcomes.","[{'text': 'Arsenic', 'type': 'Chemical', 'start': 69, 'end': 76, 'mesh': 'D001151'}, {'text': 'inorganic arsenic', 'type': 'Chemical', 'start': 269, 'end': 286, 'mesh': 'D001152'}, {'text': 'iAs', 'type': 'Chemical', 'start': 288, 'end': 291, 'mesh': 'D001152'}, {'text': 'Inorganic As', 'type': 'Chemical', 'start': 318, 'end': 330, 'mesh': 'D001152'}, {'text': 'iAs', 'type': 'Chemical', 'start': 569, 'end': 572, 'mesh': 'D001152'}, {'text': 'cancer', 'type': 'Disease', 'start': 659, 'end': 665, 'mesh': 'D009369'}, {'text': 'cancer', 'type': 'Disease', 'start': 773, 'end': 779, 'mesh': 'D009369'}, {'text': 'iAs', 'type': 'Chemical', 'start': 840, 'end': 843, 'mesh': 'D001152'}, {'text': 'cancer', 'type': 'Disease', 'start': 962, 'end': 968, 'mesh': 'D009369'}, {'text': 'iAs', 'type': 'Chemical', 'start': 1058, 'end': 1061, 'mesh': 'D001152'}, {'text': 'iAs', 'type': 'Chemical', 'start': 1166, 'end': 1169, 'mesh': 'D001152'}, {'text': 'cancer', 'type': 'Disease', 'start': 1183, 'end': 1189, 'mesh': 'D009369'}]"
+1101,44072,"On the antiarrhythmic activity of one N-substituted piperazine derivative of trans-2-amino-3-hydroxy-1, 2, 3, 4-tetrahydroanaphthalene.","The antiarrhythmic activity of the compound N-(trans-3-hydroxy-1,2,3,4-tetrahydro-2-naphthyl)-N-(3-oxo-3-phenyl-2-methylpropyl)-piperazine hydrochloride, referred to as P11, is studied on anaesthesized cats and Wistar albino rats, as well as on non-anaesthesized rabbits. Four types of experimental arrhythmia are used--with BaCl2, with chloroform-adrenaline, with strophantine G and with aconitine. The compound P11 is introduced in doses of 0.25 and 0.50 mg/kg intravenously and 10 mg/kg orally. The compound manifests antiarrhythmic activity in all models of experimental arrhythmia used, causing greatest inhibition on the arrhythmia induced by chloroform-adrenaline (in 90 per cent) and with BaCl2 (in 84 per cent). The results obtained are associated with the beta-adrenoblocking and with the membrane-stabilizing action of the compound.","[{'text': 'piperazine', 'type': 'Chemical', 'start': 52, 'end': 62, 'mesh': 'C034930'}, {'text': 'trans-2-amino-3-hydroxy-1, 2, 3, 4-tetrahydroanaphthalene', 'type': 'Chemical', 'start': 77, 'end': 134, 'mesh': '-1'}, {'text': 'N-(trans-3-hydroxy-1,2,3,4-tetrahydro-2-naphthyl)-N-(3-oxo-3-phenyl-2-methylpropyl)-piperazine hydrochloride', 'type': 'Chemical', 'start': 180, 'end': 288, 'mesh': 'C013741'}, {'text': 'P11', 'type': 'Chemical', 'start': 305, 'end': 308, 'mesh': 'C013741'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 435, 'end': 445, 'mesh': 'D001145'}, {'text': 'BaCl2', 'type': 'Chemical', 'start': 461, 'end': 466, 'mesh': 'C024986'}, {'text': 'chloroform', 'type': 'Chemical', 'start': 473, 'end': 483, 'mesh': 'D002725'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 484, 'end': 494, 'mesh': 'D004837'}, {'text': 'strophantine G', 'type': 'Chemical', 'start': 501, 'end': 515, 'mesh': 'D010042'}, {'text': 'aconitine', 'type': 'Chemical', 'start': 525, 'end': 534, 'mesh': 'D000157'}, {'text': 'P11', 'type': 'Chemical', 'start': 549, 'end': 552, 'mesh': 'C013741'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 711, 'end': 721, 'mesh': 'D001145'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 763, 'end': 773, 'mesh': 'D001145'}, {'text': 'chloroform', 'type': 'Chemical', 'start': 785, 'end': 795, 'mesh': 'D002725'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 796, 'end': 806, 'mesh': 'D004837'}, {'text': 'BaCl2', 'type': 'Chemical', 'start': 833, 'end': 838, 'mesh': 'C024986'}]"
+1102,753803,Experimental progressive muscular dystrophy and its treatment with high doses anabolizing agents.,"We are still a long way from discovering an unequivocal pathogenetic interpretation of progressive muscular dystrophy in man. Noteworthy efforts have been made in the experimental field; a recessive autosomic form found in the mouse seems to bear the closest resemblance to the human form from the genetic point of view. Myopathy due to lack of vitamin E and myopathy induced by certain viruses have much in common anatomically and pathologically with the human form. The authors induced myodystrophy in the rat by giving it a diet lacking in vitamin E. The pharmacological characteristics of vitamin E and the degenerative changes brought about by its deficiency, especially in the muscles, are illustrated. It is thus confirmed that the histological characteristics of myopathic rat muscle induced experimentally are extraordinarily similar to those of human myopathy as confirmed during biopsies performed at the Orthopaedic Traumatological Centre, Florence. The encouraging results obtained in various authoratative departments in myopathic patients by using anabolizing steroids have encouraged the authors to investigate the beneficial effects of one anabolizing agent (Dianabol, CIBA) at high doses in rats rendered myopathic by a diet deficient in vitamin E. In this way they obtained appreciable changes in body weight (increased from 50 to 70 g after forty days at a dose of 5 mg per day of anabolizing agent), but most of all they found histological changes due to ""regenerative"" changes in the muscle tissue, which however maintained its myopathic characteristics in the control animals that were not treated with the anabolizing agent. The authors conclude by affirming the undoubted efficacy of the anabolizing steroids in experimental myopathic disease, but they have reservations as to the transfer of the results into the human field, where high dosage cannot be carried out continuously because of the effects of the drug on virility; because the tissue injury too often occurs at an irreversible stage vis-a-vis the ""regeneration"" of the muscle tissue; and finally because the dystrophic injurious agent is certainly not the lack of vitamin E but something as yet unknown.","[{'text': 'muscular dystrophy', 'type': 'Disease', 'start': 25, 'end': 43, 'mesh': 'D009136'}, {'text': 'muscular dystrophy', 'type': 'Disease', 'start': 197, 'end': 215, 'mesh': 'D009136'}, {'text': 'Myopathy', 'type': 'Disease', 'start': 419, 'end': 427, 'mesh': 'D009135'}, {'text': 'vitamin E', 'type': 'Chemical', 'start': 443, 'end': 452, 'mesh': 'D014810'}, {'text': 'myopathy', 'type': 'Disease', 'start': 457, 'end': 465, 'mesh': 'D009135'}, {'text': 'myodystrophy', 'type': 'Disease', 'start': 586, 'end': 598, 'mesh': 'D009136'}, {'text': 'vitamin E', 'type': 'Chemical', 'start': 641, 'end': 650, 'mesh': 'D014810'}, {'text': 'vitamin E', 'type': 'Chemical', 'start': 691, 'end': 700, 'mesh': 'D014810'}, {'text': 'myopathic', 'type': 'Disease', 'start': 869, 'end': 878, 'mesh': 'D009135'}, {'text': 'myopathy', 'type': 'Disease', 'start': 959, 'end': 967, 'mesh': 'D009135'}, {'text': 'myopathic', 'type': 'Disease', 'start': 1133, 'end': 1142, 'mesh': 'D009135'}, {'text': 'steroids', 'type': 'Chemical', 'start': 1173, 'end': 1181, 'mesh': 'D013256'}, {'text': 'Dianabol', 'type': 'Chemical', 'start': 1274, 'end': 1282, 'mesh': 'D008696'}, {'text': 'CIBA', 'type': 'Chemical', 'start': 1284, 'end': 1288, 'mesh': '-1'}, {'text': 'myopathic', 'type': 'Disease', 'start': 1321, 'end': 1330, 'mesh': 'D009135'}, {'text': 'vitamin E', 'type': 'Chemical', 'start': 1354, 'end': 1363, 'mesh': 'D014810'}, {'text': 'myopathic', 'type': 'Disease', 'start': 1648, 'end': 1657, 'mesh': 'D009135'}, {'text': 'steroids', 'type': 'Chemical', 'start': 1823, 'end': 1831, 'mesh': 'D013256'}, {'text': 'myopathic disease', 'type': 'Disease', 'start': 1848, 'end': 1865, 'mesh': 'D009135'}, {'text': 'vitamin E', 'type': 'Chemical', 'start': 2250, 'end': 2259, 'mesh': 'D014810'}]"
+1103,920167,Fetal risks due to warfarin therapy during pregnancy.,"Two mothers with heart valve prosthesis were treated with warfarin during pregnancy. In the first case a caesarean section was done one week after replacement of warfarin with heparin. The baby died of cerebral and pulmonary hemorrhage. The second mother had a male infant by caesarean section. The baby showed warfarin-induced embryopathy with nasal hypoplasia and stippled epiphyses (chondrodysplasia punctata). Nasal hypoplasia with or without stippled epiphyses has now been reported in 11 infants born to mothers treated with warfarin during the first trimester, and a causal association is probable. In view of the risks to both mother and fetus in women with prosthetic cardiac valves it is recommended that therapeutic abortion be advised as the first alternative.","[{'text': 'warfarin', 'type': 'Chemical', 'start': 19, 'end': 27, 'mesh': 'D014859'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 112, 'end': 120, 'mesh': 'D014859'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 216, 'end': 224, 'mesh': 'D014859'}, {'text': 'heparin', 'type': 'Chemical', 'start': 230, 'end': 237, 'mesh': 'D006493'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 365, 'end': 373, 'mesh': 'D014859'}, {'text': 'embryopathy', 'type': 'Disease', 'start': 382, 'end': 393, 'mesh': 'D005315'}, {'text': 'nasal hypoplasia', 'type': 'Disease', 'start': 399, 'end': 415, 'mesh': '-1'}, {'text': 'stippled epiphyses', 'type': 'Disease', 'start': 420, 'end': 438, 'mesh': 'D002806'}, {'text': 'chondrodysplasia punctata', 'type': 'Disease', 'start': 440, 'end': 465, 'mesh': 'D002806'}, {'text': 'Nasal hypoplasia', 'type': 'Disease', 'start': 468, 'end': 484, 'mesh': '-1'}, {'text': 'stippled epiphyses', 'type': 'Disease', 'start': 501, 'end': 519, 'mesh': 'D002806'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 585, 'end': 593, 'mesh': 'D014859'}]"
+1104,1451544,Isradipine treatment for hypertension in general practice in Hong Kong.,"A 6-week open study of the introduction of isradipine treatment was conducted in general practice in Hong Kong. 303 Chinese patients with mild to moderate hypertension entered the study. Side effects were reported in 21% of patients and caused withdrawal from the study in 3 patients. The main side-effects were headache, dizziness, palpitation and flushing and these were not more frequent than reported in other studies with isradipine or with placebo. Supine blood pressure was reduced (P less than 0.01) from 170 +/- 20/102 +/- 6 mmHg to 153 +/- 19/92 +/- 8, 147 +/- 18/88 +/- 7 and 144 +/- 14/87 +/- 6 mmHg at 2, 4 and 6 weeks respectively in evaluable patients. Similar reductions occurred in standing blood pressure and there was no evidence of postural hypotension. Normalization and responder rates at 6 weeks were 86% and 69% respectively. Dosage was increased from 2.5 mg b.d. to 5 mg b.d. at 4 weeks in patients with diastolic blood pressure greater than 90 mmHg and their further response was greater than those remaining on 2.5 mg b.d.","[{'text': 'Isradipine', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D017275'}, {'text': 'hypertension', 'type': 'Disease', 'start': 25, 'end': 37, 'mesh': 'D006973'}, {'text': 'isradipine', 'type': 'Chemical', 'start': 115, 'end': 125, 'mesh': 'D017275'}, {'text': 'hypertension', 'type': 'Disease', 'start': 227, 'end': 239, 'mesh': 'D006973'}, {'text': 'headache', 'type': 'Disease', 'start': 384, 'end': 392, 'mesh': 'D006261'}, {'text': 'dizziness', 'type': 'Disease', 'start': 394, 'end': 403, 'mesh': 'D004244'}, {'text': 'palpitation', 'type': 'Disease', 'start': 405, 'end': 416, 'mesh': '-1'}, {'text': 'flushing', 'type': 'Disease', 'start': 421, 'end': 429, 'mesh': 'D005483'}, {'text': 'isradipine', 'type': 'Chemical', 'start': 499, 'end': 509, 'mesh': 'D017275'}, {'text': 'postural hypotension', 'type': 'Disease', 'start': 824, 'end': 844, 'mesh': 'D007024'}]"
+1105,2782734,Tachyphylaxis to systemic but not to airway responses during prolonged therapy with high dose inhaled salbutamol in asthmatics.,"High doses of inhaled salbutamol produce substantial improvements in airway response in patients with asthma, and are associated with dose-dependent systemic beta-adrenoceptor responses. The purpose of the present study was to investigate whether tachyphylaxis occurs during prolonged treatment with high dose inhaled salbutamol. Twelve asthmatic patients (FEV1, 81 +/- 4% predicted), requiring only occasional inhaled beta-agonists as their sole therapy, were given a 14-day treatment with high dose inhaled salbutamol (HDS), 4,000 micrograms daily, low dose inhaled salbutamol (LDS), 800 micrograms daily, or placebo (PI) by metered-dose inhaler in a double-blind, randomized crossover design. During the 14-day run-in and during washout periods, inhaled beta-agonists were withheld and ipratropium bromide was substituted for rescue purposes. At the end of each 14-day treatment, a dose-response curve (DRC) was performed, and airway (FEV1, FEF25-75) chronotropic (HR), tremor, and metabolic (K, Glu) responses were measured at each step (from 100 to 4,000 micrograms). Treatment had no significant effect on baseline values. There were dose-dependent increases in FEV1 and FEF25-75 (p less than 0.001), and pretreatment with HDS did not displace the DRC to the right. DRC for HR (p less than 0.001), K (p less than 0.001), and Glu (p less than 0.005) were attenuated after treatment with HDS compared with PI. There were also differences between HDS and LDS for HR (p less than 0.001) and Glu (p less than 0.05) responses. Frequency and severity of subjective adverse effects were also reduced after HDS: tremor (p less than 0.001), palpitations (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)","[{'text': 'salbutamol', 'type': 'Chemical', 'start': 102, 'end': 112, 'mesh': 'D000420'}, {'text': 'asthmatics', 'type': 'Disease', 'start': 116, 'end': 126, 'mesh': 'D001249'}, {'text': 'salbutamol', 'type': 'Chemical', 'start': 150, 'end': 160, 'mesh': 'D000420'}, {'text': 'asthma', 'type': 'Disease', 'start': 230, 'end': 236, 'mesh': 'D001249'}, {'text': 'salbutamol', 'type': 'Chemical', 'start': 446, 'end': 456, 'mesh': 'D000420'}, {'text': 'asthmatic', 'type': 'Disease', 'start': 465, 'end': 474, 'mesh': 'D001249'}, {'text': 'salbutamol', 'type': 'Chemical', 'start': 637, 'end': 647, 'mesh': 'D000420'}, {'text': 'salbutamol', 'type': 'Chemical', 'start': 696, 'end': 706, 'mesh': 'D000420'}, {'text': 'ipratropium bromide', 'type': 'Chemical', 'start': 917, 'end': 936, 'mesh': 'D009241'}, {'text': 'tremor', 'type': 'Disease', 'start': 1101, 'end': 1107, 'mesh': 'D014202'}, {'text': 'K', 'type': 'Chemical', 'start': 1124, 'end': 1125, 'mesh': 'D011188'}, {'text': 'Glu', 'type': 'Chemical', 'start': 1127, 'end': 1130, 'mesh': 'D005947'}, {'text': 'K', 'type': 'Chemical', 'start': 1432, 'end': 1433, 'mesh': 'D011188'}, {'text': 'Glu', 'type': 'Chemical', 'start': 1459, 'end': 1462, 'mesh': 'D005947'}, {'text': 'Glu', 'type': 'Chemical', 'start': 1621, 'end': 1624, 'mesh': 'D005947'}, {'text': 'tremor', 'type': 'Disease', 'start': 1737, 'end': 1743, 'mesh': 'D014202'}, {'text': 'palpitations', 'type': 'Disease', 'start': 1765, 'end': 1777, 'mesh': '-1'}]"
+1106,2983630,Increased anxiogenic effects of caffeine in panic disorders.,"The effects of oral administration of caffeine (10 mg/kg) on behavioral ratings, somatic symptoms, blood pressure and plasma levels of 3-methoxy-4-hydroxyphenethyleneglycol (MHPG) and cortisol were determined in 17 healthy subjects and 21 patients meeting DSM-III criteria for agoraphobia with panic attacks or panic disorder. Caffeine produced significantly greater increases in subject-rated anxiety, nervousness, fear, nausea, palpitations, restlessness, and tremors in the patients compared with healthy subjects. In the patients, but not the healthy subjects, these symptoms were significantly correlated with plasma caffeine levels. Seventy-one percent of the patients reported that the behavioral effects of caffeine were similar to those experienced during panic attacks. Caffeine did not alter plasma MHPG levels in either the healthy subjects or patients. Caffeine increased plasma cortisol levels equally in the patient and healthy groups. Because caffeine is an adenosine receptor antagonist, these results suggest that some panic disorder patients may have abnormalities in neuronal systems involving adenosine. Patients with anxiety disorders may benefit by avoiding caffeine-containing foods and beverages.","[{'text': 'caffeine', 'type': 'Chemical', 'start': 32, 'end': 40, 'mesh': 'D002110'}, {'text': 'panic disorders', 'type': 'Disease', 'start': 44, 'end': 59, 'mesh': 'D016584'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 99, 'end': 107, 'mesh': 'D002110'}, {'text': '3-methoxy-4-hydroxyphenethyleneglycol', 'type': 'Chemical', 'start': 196, 'end': 233, 'mesh': 'D008734'}, {'text': 'MHPG', 'type': 'Chemical', 'start': 235, 'end': 239, 'mesh': 'D008734'}, {'text': 'cortisol', 'type': 'Chemical', 'start': 245, 'end': 253, 'mesh': 'D006854'}, {'text': 'agoraphobia', 'type': 'Disease', 'start': 338, 'end': 349, 'mesh': 'D000379'}, {'text': 'panic attacks', 'type': 'Disease', 'start': 355, 'end': 368, 'mesh': 'D016584'}, {'text': 'panic disorder', 'type': 'Disease', 'start': 372, 'end': 386, 'mesh': 'D016584'}, {'text': 'Caffeine', 'type': 'Chemical', 'start': 388, 'end': 396, 'mesh': 'D002110'}, {'text': 'anxiety', 'type': 'Disease', 'start': 455, 'end': 462, 'mesh': 'D001008'}, {'text': 'nausea', 'type': 'Disease', 'start': 483, 'end': 489, 'mesh': 'D009325'}, {'text': 'palpitations', 'type': 'Disease', 'start': 491, 'end': 503, 'mesh': '-1'}, {'text': 'restlessness', 'type': 'Disease', 'start': 505, 'end': 517, 'mesh': 'D011595'}, {'text': 'tremors', 'type': 'Disease', 'start': 523, 'end': 530, 'mesh': 'D014202'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 683, 'end': 691, 'mesh': 'D002110'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 776, 'end': 784, 'mesh': 'D002110'}, {'text': 'panic attacks', 'type': 'Disease', 'start': 826, 'end': 839, 'mesh': 'D016584'}, {'text': 'Caffeine', 'type': 'Chemical', 'start': 841, 'end': 849, 'mesh': 'D002110'}, {'text': 'MHPG', 'type': 'Chemical', 'start': 871, 'end': 875, 'mesh': 'D008734'}, {'text': 'Caffeine', 'type': 'Chemical', 'start': 927, 'end': 935, 'mesh': 'D002110'}, {'text': 'cortisol', 'type': 'Chemical', 'start': 953, 'end': 961, 'mesh': 'D006854'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1020, 'end': 1028, 'mesh': 'D002110'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 1035, 'end': 1044, 'mesh': 'D000241'}, {'text': 'panic disorder', 'type': 'Disease', 'start': 1098, 'end': 1112, 'mesh': 'D016584'}, {'text': 'abnormalities in neuronal systems', 'type': 'Disease', 'start': 1131, 'end': 1164, 'mesh': 'D009421'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 1175, 'end': 1184, 'mesh': 'D000241'}, {'text': 'anxiety disorders', 'type': 'Disease', 'start': 1200, 'end': 1217, 'mesh': 'D001008'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1242, 'end': 1250, 'mesh': 'D002110'}]"
+1107,3711722,Human and canine ventricular vasoactive intestinal polypeptide: decrease with heart failure.,"Vasoactive intestinal polypeptide (VIP) is a systemic and coronary vasodilator that may have positive inotropic properties. Myocardial levels of VIP were assayed before and after the development of heart failure in two canine models. In the first, cobalt cardiomyopathy was induced in eight dogs; VIP (by radioimmunoassay) decreased from 35 +/- 11 pg/mg protein (mean +/- SD) to 5 +/- 4 pg/mg protein (P less than 0.05). In six dogs with doxorubicin-induced heart failure, VIP decreased from 31 +/- 7 to 11 +/- 4 pg/mg protein (P less than 0.05). In addition, VIP content of left ventricular muscle of resected failing hearts in 10 patients receiving a heart transplant was compared with the papillary muscles in 14 patients (five with rheumatic disease, nine with myxomatous degeneration) receiving mitral valve prostheses. The lowest myocardial VIP concentration was found in the hearts of patients with coronary disease (one patient receiving a transplant and three receiving mitral prostheses) (6.3 +/- 1.9 pg/mg protein). The other patients undergoing transplantation had an average ejection fraction of 17% +/- 6% and a VIP level of 8.8 +/- 3.9 pg/mg protein. The hearts without coronary artery disease (average ejection fraction of this group 62% +/- 10%) had a VIP concentration of 14.1 +/- 7.9 pg/mg protein, and this was greater than in hearts of the patients with coronary disease and the hearts of patients receiving a transplant (P less than 0.05). Myocardial catecholamines were also determined in 14 subjects; a weak correlation (r = 0.57, P less than 0.05) between the tissue concentrations of VIP and norepinephrine was noted.(ABSTRACT TRUNCATED AT 250 WORDS)","[{'text': 'heart failure', 'type': 'Disease', 'start': 78, 'end': 91, 'mesh': 'D006333'}, {'text': 'heart failure', 'type': 'Disease', 'start': 291, 'end': 304, 'mesh': 'D006333'}, {'text': 'cobalt', 'type': 'Chemical', 'start': 341, 'end': 347, 'mesh': 'D003035'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 348, 'end': 362, 'mesh': 'D009202'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 531, 'end': 542, 'mesh': 'D004317'}, {'text': 'heart failure', 'type': 'Disease', 'start': 551, 'end': 564, 'mesh': 'D006333'}, {'text': 'rheumatic disease', 'type': 'Disease', 'start': 829, 'end': 846, 'mesh': 'D012216'}, {'text': 'myxomatous degeneration', 'type': 'Disease', 'start': 858, 'end': 881, 'mesh': '-1'}, {'text': 'coronary disease', 'type': 'Disease', 'start': 999, 'end': 1015, 'mesh': 'D003327'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 1278, 'end': 1301, 'mesh': 'D003324'}, {'text': 'coronary disease', 'type': 'Disease', 'start': 1468, 'end': 1484, 'mesh': 'D003327'}, {'text': 'catecholamines', 'type': 'Chemical', 'start': 1566, 'end': 1580, 'mesh': 'D002395'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 1711, 'end': 1725, 'mesh': 'D009638'}]"
+1108,6728873,Interstrain variation in acute toxic response to caffeine among inbred mice.,"Acute toxic dosage-dependent behavioral effects of caffeine were compared in adult males from seven inbred mouse strains (A/J, BALB/cJ, CBA/J, C3H/HeJ, C57BL/6J, DBA/2J, SWR/J). C57BL/6J, chosen as a ""prototypic"" mouse strain, was used to determine behavioral responses to a broad range (5-500 mg/kg) of caffeine doses. Five phenotypic characteristics--locomotor activity, righting ability, clonic seizure induction, stress-induced lethality, death without external stress--were scored at various caffeine doses in drug-naive animals under empirically optimized, rigidly constant experimental conditions. Mice (n = 12 for each point) received single IP injections of a fixed volume/g body weight of physiological saline carrier with or without caffeine in doses ranging from 125-500 mg/kg. Loss of righting ability was scored at 1, 3, 5 min post dosing and at 5 min intervals thereafter for 20 min. In the same animals the occurrence of clonic seizures was scored as to time of onset and severity for 20 min after drug administration. When these proceeded to tonic seizures, death occurred in less than 20 min. Animals surviving for 20 min were immediately stressed by a swim test in 25 degrees C water, and death-producing tonic seizures were scored for 2 min. In other animals locomotor activity was measured 15 or 60 min after caffeine administration. By any single behavioral criterion or a combination of these criteria, marked differences in response to toxic caffeine doses were observed between strains. These results indicate that behavioral toxicity testing of alkylxanthines in a single mouse strain may be misleading and suggest that toxic responses of the central nervous system to this class of compounds are genetically influenced in mammals.","[{'text': 'caffeine', 'type': 'Chemical', 'start': 49, 'end': 57, 'mesh': 'D002110'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 128, 'end': 136, 'mesh': 'D002110'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 381, 'end': 389, 'mesh': 'D002110'}, {'text': 'clonic seizure', 'type': 'Disease', 'start': 468, 'end': 482, 'mesh': 'D012640'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 574, 'end': 582, 'mesh': 'D002110'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 821, 'end': 829, 'mesh': 'D002110'}, {'text': 'clonic seizures', 'type': 'Disease', 'start': 1014, 'end': 1029, 'mesh': 'D012640'}, {'text': 'tonic seizures', 'type': 'Disease', 'start': 1136, 'end': 1150, 'mesh': 'D012640'}, {'text': 'tonic seizures', 'type': 'Disease', 'start': 1301, 'end': 1315, 'mesh': 'D012640'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1407, 'end': 1415, 'mesh': 'D002110'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1543, 'end': 1551, 'mesh': 'D002110'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1628, 'end': 1636, 'mesh': 'D064420'}, {'text': 'alkylxanthines', 'type': 'Chemical', 'start': 1648, 'end': 1662, 'mesh': '-1'}]"
+1109,7248895,Invasive carcinoma of the renal pelvis following cyclophosphamide therapy for nonmalignant disease.,"A 47-year-old woman with right hydroureteronephrosis due to ureterovesical junction obstruction had gross hematuria after being treated for five years wtih cyclophosphamide for cerebral vasculitis. A right nephroureterectomy was required for control of bleeding. The pathology specimen contained clinically occult invasive carcinoma of the renal pelvis. Although the ability of cyclophosphamide to cause hemorrhagic cystitis and urine cytologic abnormalities indistinguishable from high grade carcinoma is well known, it is less widely appreciated that it is also associated with carcinoma of the urinary tract. Twenty carcinomas of the urinary bladder and one carcinoma of the prostate have been reported in association with its use. The present case is the first carcinoma of the renal pelvis reported in association with cyclophosphamide treatment. It is the third urinary tract cancer reported in association with cyclophosphamide treatment for nonmalignant disease. The association of the tumor with preexisting hydroureteronephrosis suggests that stasis prolonged and intensified exposure of upper urinary tract epithelium to cyclophosphamide. Patients who are candidates for long-term cyclophosphamide treatment should be routinely evaluated for obstructive uropathy.","[{'text': 'carcinoma of the renal pelvis', 'type': 'Disease', 'start': 9, 'end': 38, 'mesh': 'D010386'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 49, 'end': 65, 'mesh': 'D003520'}, {'text': 'hydroureteronephrosis', 'type': 'Disease', 'start': 131, 'end': 152, 'mesh': 'D006869'}, {'text': 'hematuria', 'type': 'Disease', 'start': 206, 'end': 215, 'mesh': 'D006417'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 256, 'end': 272, 'mesh': 'D003520'}, {'text': 'cerebral vasculitis', 'type': 'Disease', 'start': 277, 'end': 296, 'mesh': 'D020293'}, {'text': 'bleeding', 'type': 'Disease', 'start': 353, 'end': 361, 'mesh': 'D006470'}, {'text': 'carcinoma of the renal pelvis', 'type': 'Disease', 'start': 423, 'end': 452, 'mesh': 'D010386'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 478, 'end': 494, 'mesh': 'D003520'}, {'text': 'carcinoma', 'type': 'Disease', 'start': 593, 'end': 602, 'mesh': 'D002277'}, {'text': 'carcinoma of the urinary tract', 'type': 'Disease', 'start': 680, 'end': 710, 'mesh': 'D014571'}, {'text': 'carcinomas of the urinary bladder', 'type': 'Disease', 'start': 719, 'end': 752, 'mesh': 'D001749'}, {'text': 'carcinoma of the prostate', 'type': 'Disease', 'start': 761, 'end': 786, 'mesh': 'D011471'}, {'text': 'carcinoma of the renal pelvis', 'type': 'Disease', 'start': 865, 'end': 894, 'mesh': 'D010386'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 924, 'end': 940, 'mesh': 'D003520'}, {'text': 'urinary tract cancer', 'type': 'Disease', 'start': 968, 'end': 988, 'mesh': 'D014571'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 1018, 'end': 1034, 'mesh': 'D003520'}, {'text': 'tumor', 'type': 'Disease', 'start': 1094, 'end': 1099, 'mesh': 'D009369'}, {'text': 'hydroureteronephrosis', 'type': 'Disease', 'start': 1117, 'end': 1138, 'mesh': 'D006869'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 1232, 'end': 1248, 'mesh': 'D003520'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 1292, 'end': 1308, 'mesh': 'D003520'}, {'text': 'obstructive uropathy', 'type': 'Disease', 'start': 1353, 'end': 1373, 'mesh': '-1'}]"
+1110,9578276,Ascending dose tolerance study of intramuscular carbetocin administered after normal vaginal birth.,"OBJECTIVE: To determine the maximum tolerated dose (MTD) of carbetocin (a long-acting synthetic analogue of oxytocin), when administered immediately after vaginal delivery at term. MATERIALS AND METHODS: Carbetocin was given as an intramuscular injection immediately after the birth of the infant in 45 healthy women with normal singleton pregnancies who delivered vaginally at term. Dosage groups of 15, 30, 50, 75, 100, 125, 150, 175 or 200 microg carbetocin were assigned to blocks of three women according to the continual reassessment method (CRM). RESULTS: All dosage groups consisted of three women, except those with 100 microg (n=6) and 200 microg (n=18). Recorded were dose-limiting adverse events: hyper- or hypotension (three), severe abdominal pain (0), vomiting (0) and retained placenta (four). Serious adverse events occurred in seven women: six cases with blood loss > or = 1000 ml, four cases of manual placenta removal, five cases of additional oxytocics administration and five cases of blood transfusion. Maximum blood loss was greatest at the upper and lower dose levels, and lowest in the 70-125 microg dose range. Four out of six cases with blood loss > or = 1000 ml occurred in the 200 microg group. The majority of additional administration of oxytocics (4/5) and blood transfusion (3/5) occurred in the dose groups of 200 microg. All retained placentae were found in the group of 200 microg. CONCLUSION: The MTD was calculated to be at 200 microg carbetocin.","[{'text': 'carbetocin', 'type': 'Chemical', 'start': 48, 'end': 58, 'mesh': 'C020731'}, {'text': 'carbetocin', 'type': 'Chemical', 'start': 160, 'end': 170, 'mesh': 'C020731'}, {'text': 'oxytocin', 'type': 'Chemical', 'start': 208, 'end': 216, 'mesh': 'D010121'}, {'text': 'Carbetocin', 'type': 'Chemical', 'start': 304, 'end': 314, 'mesh': 'C020731'}, {'text': 'carbetocin', 'type': 'Chemical', 'start': 550, 'end': 560, 'mesh': 'C020731'}, {'text': 'hyper- or hypotension', 'type': 'Disease', 'start': 809, 'end': 830, 'mesh': 'D006973|D007022'}, {'text': 'abdominal pain', 'type': 'Disease', 'start': 847, 'end': 861, 'mesh': 'D015746'}, {'text': 'vomiting', 'type': 'Disease', 'start': 867, 'end': 875, 'mesh': 'D014839'}, {'text': 'retained placenta', 'type': 'Disease', 'start': 884, 'end': 901, 'mesh': 'D018457'}, {'text': 'blood loss', 'type': 'Disease', 'start': 973, 'end': 983, 'mesh': 'D006473'}, {'text': 'blood loss', 'type': 'Disease', 'start': 1134, 'end': 1144, 'mesh': 'D006473'}, {'text': 'blood loss', 'type': 'Disease', 'start': 1265, 'end': 1275, 'mesh': 'D006473'}, {'text': 'carbetocin', 'type': 'Chemical', 'start': 1574, 'end': 1584, 'mesh': 'C020731'}]"
+1111,11423811,A pilot study to assess the safety of dobutamine stress echocardiography in the emergency department evaluation of cocaine-associated chest pain.,"STUDY OBJECTIVE: Chest pain in the setting of cocaine use poses a diagnostic dilemma. Dobutamine stress echocardiography (DSE) is a widely available and sensitive test for evaluating cardiac ischemia. Because of the theoretical concern regarding administration of dobutamine in the setting of cocaine use, we conducted a pilot study to assess the safety of DSE in emergency department patients with cocaine-associated chest pain. METHODS: A prospective case series was conducted in the intensive diagnostic and treatment unit in the ED of an urban tertiary-care teaching hospital. Patients were eligible for DSE if they had used cocaine within 24 hours preceding the onset of chest pain and had a normal ECG and tropinin I level. Patients exhibiting signs of continuing cocaine toxicity were excluded from the study. All patients were admitted to the hospital for serial testing after the DSE testing in the intensive diagnostic and treatment unit. RESULTS: Twenty-four patients were enrolled. Two patients had inadequate resting images, one DSE was terminated because of inferior hypokinesis, another DSE was terminated because of a rate-related atrial conduction deficit, and 1 patient did not reach the target heart rate. Thus, 19 patients completed a DSE and reached their target heart rates. None of the patients experienced signs of exaggerated adrenergic response, which was defined as a systolic blood pressure of greater than 200 mm Hg or the occurrence of tachydysrhythmias (excluding sinus tachycardia). Further suggesting lack of exaggerated adrenergic response, 13 (65%) of 20 patients required supplemental atropine to reach their target heart rates. CONCLUSION: No exaggerated adrenergic response was detected when dobutamine was administered to patients with cocaine-related chest pain.","[{'text': 'dobutamine', 'type': 'Chemical', 'start': 38, 'end': 48, 'mesh': 'D004280'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 115, 'end': 122, 'mesh': 'D003042'}, {'text': 'chest pain', 'type': 'Disease', 'start': 134, 'end': 144, 'mesh': 'D002637'}, {'text': 'Chest pain', 'type': 'Disease', 'start': 163, 'end': 173, 'mesh': 'D002637'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 192, 'end': 199, 'mesh': 'D003042'}, {'text': 'Dobutamine', 'type': 'Chemical', 'start': 232, 'end': 242, 'mesh': 'D004280'}, {'text': 'ischemia', 'type': 'Disease', 'start': 337, 'end': 345, 'mesh': 'D007511'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 410, 'end': 420, 'mesh': 'D004280'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 439, 'end': 446, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 545, 'end': 552, 'mesh': 'D003042'}, {'text': 'chest pain', 'type': 'Disease', 'start': 564, 'end': 574, 'mesh': 'D002637'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 775, 'end': 782, 'mesh': 'D003042'}, {'text': 'chest pain', 'type': 'Disease', 'start': 822, 'end': 832, 'mesh': 'D002637'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 916, 'end': 923, 'mesh': 'D003042'}, {'text': 'toxicity', 'type': 'Disease', 'start': 924, 'end': 932, 'mesh': 'D064420'}, {'text': 'hypokinesis', 'type': 'Disease', 'start': 1227, 'end': 1238, 'mesh': 'D018476'}, {'text': 'tachydysrhythmias', 'type': 'Disease', 'start': 1612, 'end': 1629, 'mesh': '-1'}, {'text': 'sinus tachycardia', 'type': 'Disease', 'start': 1641, 'end': 1658, 'mesh': 'D013616'}, {'text': 'atropine', 'type': 'Chemical', 'start': 1767, 'end': 1775, 'mesh': 'D001285'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 1876, 'end': 1886, 'mesh': 'D004280'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1921, 'end': 1928, 'mesh': 'D003042'}, {'text': 'chest pain', 'type': 'Disease', 'start': 1937, 'end': 1947, 'mesh': 'D002637'}]"
+1112,12678199,Amiodarone-induced torsade de pointes during bladder irrigation: an unusual presentation--a case report.,"The authors present a case of early (within 4 days) development of torsade de pointes (TdP) associated with oral amiodarone therapy. Consistent with other reports this case of TdP occurred in the context of multiple exacerbating factors including hypokalemia and digoxin excess. Transient prolongation of the QT during bladder irrigation prompted the episode of TdP. It is well known that bradycardia exacerbates acquired TdP. The authors speculate that the increased vagal tone during bladder irrigation, a vagal maneuver, in the context of amiodarone therapy resulted in amiodarone-induced proarrhythmia. In the absence of amiodarone therapy, a second bladder irrigation did not induce TdP despite hypokalemia and hypomagnesemia.","[{'text': 'Amiodarone', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D000638'}, {'text': 'torsade de pointes', 'type': 'Disease', 'start': 19, 'end': 37, 'mesh': 'D016171'}, {'text': 'torsade de pointes', 'type': 'Disease', 'start': 172, 'end': 190, 'mesh': 'D016171'}, {'text': 'TdP', 'type': 'Disease', 'start': 192, 'end': 195, 'mesh': 'D016171'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 218, 'end': 228, 'mesh': 'D000638'}, {'text': 'TdP', 'type': 'Disease', 'start': 281, 'end': 284, 'mesh': 'D016171'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 352, 'end': 363, 'mesh': 'D007008'}, {'text': 'digoxin', 'type': 'Chemical', 'start': 368, 'end': 375, 'mesh': 'D004077'}, {'text': 'TdP', 'type': 'Disease', 'start': 467, 'end': 470, 'mesh': 'D016171'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 494, 'end': 505, 'mesh': 'D001919'}, {'text': 'TdP', 'type': 'Disease', 'start': 527, 'end': 530, 'mesh': 'D016171'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 647, 'end': 657, 'mesh': 'D000638'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 678, 'end': 688, 'mesh': 'D000638'}, {'text': 'proarrhythmia', 'type': 'Disease', 'start': 697, 'end': 710, 'mesh': '-1'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 730, 'end': 740, 'mesh': 'D000638'}, {'text': 'TdP', 'type': 'Disease', 'start': 793, 'end': 796, 'mesh': 'D016171'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 805, 'end': 816, 'mesh': 'D007008'}, {'text': 'hypomagnesemia', 'type': 'Disease', 'start': 821, 'end': 835, 'mesh': 'C537153'}]"
+1113,15696449,Acute renal insufficiency after high-dose melphalan in patients with primary systemic amyloidosis during stem cell transplantation.,"BACKGROUND: Patients with primary systemic amyloidosis (AL) have a poor prognosis. Median survival time from standard treatments is only 17 months. High-dose intravenous melphalan followed by peripheral blood stem cell transplant (PBSCT) appears to be the most promising therapy, but treatment mortality can be high. The authors have noted the development of acute renal insufficiency immediately after melphalan conditioning. This study was undertaken to further examine its risk factors and impact on posttransplant mortality. METHODS: Consecutive AL patients who underwent PBSCT were studied retrospectively. Acute renal insufficiency (ARI) after high-dose melphalan was defined by a minimum increase of 0.5 mg/dL (44 micromol/L) in the serum creatinine level that is greater than 50% of baseline immediately after conditioning. Urine sediment score was the sum of the individual types of sediment identified on urine microscopy. RESULTS: Of the 80 patients studied, ARI developed in 18.8% of the patients after high-dose melphalan. Univariate analysis identified age, hypoalbuminemia, heavy proteinuria, diuretic use, and urine sediment score (>3) as risk factors. Age and urine sediment score remained independently significant risk factors in the multivariate analysis. Patients who had ARI after high-dose melphalan underwent dialysis more often (P = 0.007), and had a worse 1-year survival (P = 0.03). CONCLUSION: The timing of renal injury strongly suggests melphalan as the causative agent. Ongoing tubular injury may be a prerequisite for renal injury by melphalan as evidenced by the active urinary sediment. Development of ARI adversely affected the outcome after PBSCT. Effective preventive measures may help decrease the treatment mortality of PBSCT in AL patients.","[{'text': 'Acute renal insufficiency', 'type': 'Disease', 'start': 0, 'end': 25, 'mesh': 'D058186'}, {'text': 'melphalan', 'type': 'Chemical', 'start': 42, 'end': 51, 'mesh': 'D008558'}, {'text': 'primary systemic amyloidosis', 'type': 'Disease', 'start': 69, 'end': 97, 'mesh': 'C531616'}, {'text': 'primary systemic amyloidosis', 'type': 'Disease', 'start': 158, 'end': 186, 'mesh': 'C531616'}, {'text': 'AL', 'type': 'Disease', 'start': 188, 'end': 190, 'mesh': 'D000686'}, {'text': 'melphalan', 'type': 'Chemical', 'start': 302, 'end': 311, 'mesh': 'D008558'}, {'text': 'acute renal insufficiency', 'type': 'Disease', 'start': 491, 'end': 516, 'mesh': 'D058186'}, {'text': 'melphalan', 'type': 'Chemical', 'start': 535, 'end': 544, 'mesh': 'D008558'}, {'text': 'AL', 'type': 'Disease', 'start': 682, 'end': 684, 'mesh': 'D000686'}, {'text': 'Acute renal insufficiency', 'type': 'Disease', 'start': 744, 'end': 769, 'mesh': 'D058186'}, {'text': 'ARI', 'type': 'Disease', 'start': 771, 'end': 774, 'mesh': 'D058186'}, {'text': 'melphalan', 'type': 'Chemical', 'start': 792, 'end': 801, 'mesh': 'D008558'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 878, 'end': 888, 'mesh': 'D003404'}, {'text': 'ARI', 'type': 'Disease', 'start': 1102, 'end': 1105, 'mesh': 'D058186'}, {'text': 'melphalan', 'type': 'Chemical', 'start': 1157, 'end': 1166, 'mesh': 'D008558'}, {'text': 'hypoalbuminemia', 'type': 'Disease', 'start': 1204, 'end': 1219, 'mesh': 'D034141'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1227, 'end': 1238, 'mesh': 'D011507'}, {'text': 'ARI', 'type': 'Disease', 'start': 1425, 'end': 1428, 'mesh': 'D058186'}, {'text': 'melphalan', 'type': 'Chemical', 'start': 1445, 'end': 1454, 'mesh': 'D008558'}, {'text': 'renal injury', 'type': 'Disease', 'start': 1568, 'end': 1580, 'mesh': 'D058186'}, {'text': 'melphalan', 'type': 'Chemical', 'start': 1599, 'end': 1608, 'mesh': 'D008558'}, {'text': 'tubular injury', 'type': 'Disease', 'start': 1641, 'end': 1655, 'mesh': '-1'}, {'text': 'renal injury', 'type': 'Disease', 'start': 1682, 'end': 1694, 'mesh': 'D058186'}, {'text': 'melphalan', 'type': 'Chemical', 'start': 1698, 'end': 1707, 'mesh': 'D008558'}, {'text': 'ARI', 'type': 'Disease', 'start': 1768, 'end': 1771, 'mesh': 'D058186'}, {'text': 'AL', 'type': 'Disease', 'start': 1900, 'end': 1902, 'mesh': 'D000686'}]"
+1114,17554526,Impaired fear recognition in regular recreational cocaine users.,"INTRODUCTION: The ability to read facial expressions is essential for normal human social interaction. The aim of the present study was to conduct the first investigation of facial expression recognition performance in recreational cocaine users. MATERIALS AND METHODS: Three groups, comprised of 21 cocaine naive participants (CN),  30 occasional cocaine (OC), and 48 regular recreational cocaine (RC) users, were compared. An emotional facial expression (EFE) task consisting of a male and female face expressing six basic emotions (happiness, surprise, sadness, anger, fear, and disgust) was administered. Mean percent accuracy and latencies for correct responses across eight presentations of each basic emotion were derived. Participants were also assessed with the ""Eyes task"" to investigate their ability to recognize more complex emotional states and the Symptom CheckList-90-Revised to measure psychopathology. RESULTS: There were no group differences in psychopathology or ""eyes task"" performance, but the RC group, who otherwise had similar illicit substance use histories to the OC group, exhibited impaired fear recognition accuracy compared to the OC and CN groups. The RC group also correctly identified anger, fear, happiness, and surprise, more slowly than CN, but not OC participants. The OC group was slower than CN when correctly identifying disgust. The selective deficit in fear recognition accuracy manifested by the RC group cannot be explained by the subacute effects of cocaine, or ecstasy, because recent and less recent users of these drugs within this group were similarly impaired. Possible parallels between RC users and psychopaths with respect to impaired fear recognition, amygdala dysfunction, and etiology are discussed.","[{'text': 'Impaired fear recognition', 'type': 'Disease', 'start': 0, 'end': 25, 'mesh': 'D001925'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 50, 'end': 57, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 297, 'end': 304, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 365, 'end': 372, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 413, 'end': 420, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 455, 'end': 462, 'mesh': 'D003042'}, {'text': 'impaired fear recognition', 'type': 'Disease', 'start': 1176, 'end': 1201, 'mesh': 'D001925'}, {'text': 'deficit in fear recognition', 'type': 'Disease', 'start': 1450, 'end': 1477, 'mesh': 'D001925'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1561, 'end': 1568, 'mesh': 'D003042'}, {'text': 'ecstasy', 'type': 'Chemical', 'start': 1573, 'end': 1580, 'mesh': 'D018817'}, {'text': 'psychopaths', 'type': 'Disease', 'start': 1717, 'end': 1728, 'mesh': 'D001523'}, {'text': 'impaired fear recognition', 'type': 'Disease', 'start': 1745, 'end': 1770, 'mesh': 'D001925'}, {'text': 'amygdala dysfunction', 'type': 'Disease', 'start': 1772, 'end': 1792, 'mesh': '-1'}]"
+1115,17721298,Corneal ulcers associated with aerosolized crack cocaine use.,"PURPOSE: We report 4 cases of corneal ulcers associated with drug abuse. The pathogenesis of these ulcers and management of these patients are also reviewed. METHODS: Review of all cases of corneal ulcers associated with drug abuse seen at our institution from July 2006 to December 2006. RESULTS: Four patients with corneal ulcers associated with crack cocaine use were reviewed. All corneal ulcers were cultured, and the patients were admitted to the hospital for intensive topical antibiotic treatment. Each patient received comprehensive health care, including medical and substance abuse consultations. Streptococcal organisms were found in 3 cases and Capnocytophaga and Brevibacterium casei in 1 patient. The infections responded to antibiotic treatment. Two patients needed a lateral tarsorrhaphy for persistent epithelial defects. CONCLUSIONS: Aerosolized crack cocaine use can be associated with the development of corneal ulcers. Drug abuse provides additional challenges for management. Not only treatment of their infections but also the overall poor health of the patients and increased risk of noncompliance need to be addressed. Comprehensive care may provide the patient the opportunity to discontinue their substance abuse, improve their overall health, and prevent future corneal complications.","[{'text': 'Corneal ulcers', 'type': 'Disease', 'start': 0, 'end': 14, 'mesh': 'D003320'}, {'text': 'crack cocaine', 'type': 'Chemical', 'start': 43, 'end': 56, 'mesh': 'D016578'}, {'text': 'corneal ulcers', 'type': 'Disease', 'start': 92, 'end': 106, 'mesh': 'D003320'}, {'text': 'drug abuse', 'type': 'Disease', 'start': 123, 'end': 133, 'mesh': 'D019966'}, {'text': 'ulcers', 'type': 'Disease', 'start': 161, 'end': 167, 'mesh': 'D014456'}, {'text': 'corneal ulcers', 'type': 'Disease', 'start': 252, 'end': 266, 'mesh': 'D003320'}, {'text': 'drug abuse', 'type': 'Disease', 'start': 283, 'end': 293, 'mesh': 'D019966'}, {'text': 'corneal ulcers', 'type': 'Disease', 'start': 379, 'end': 393, 'mesh': 'D003320'}, {'text': 'crack cocaine', 'type': 'Chemical', 'start': 410, 'end': 423, 'mesh': 'D016578'}, {'text': 'corneal ulcers', 'type': 'Disease', 'start': 447, 'end': 461, 'mesh': 'D003320'}, {'text': 'substance abuse', 'type': 'Disease', 'start': 639, 'end': 654, 'mesh': 'D019966'}, {'text': 'infections', 'type': 'Disease', 'start': 778, 'end': 788, 'mesh': 'D007239'}, {'text': 'epithelial defects', 'type': 'Disease', 'start': 882, 'end': 900, 'mesh': '-1'}, {'text': 'crack cocaine', 'type': 'Chemical', 'start': 927, 'end': 940, 'mesh': 'D016578'}, {'text': 'corneal ulcers', 'type': 'Disease', 'start': 987, 'end': 1001, 'mesh': 'D003320'}, {'text': 'Drug abuse', 'type': 'Disease', 'start': 1003, 'end': 1013, 'mesh': 'D019966'}, {'text': 'infections', 'type': 'Disease', 'start': 1089, 'end': 1099, 'mesh': 'D007239'}, {'text': 'substance abuse', 'type': 'Disease', 'start': 1287, 'end': 1302, 'mesh': 'D019966'}]"
+1116,18341442,Levetiracetam as an adjunct to phenobarbital treatment in cats with suspected idiopathic epilepsy.,"OBJECTIVE: To assess pharmacokinetics, efficacy, and tolerability of oral levetiracetam administered as an adjunct to phenobarbital treatment in cats with poorly controlled suspected idiopathic epilepsy. DESIGN-Open-label, noncomparative clinical trial. ANIMALS: 12 cats suspected to have idiopathic epilepsy that was poorly controlled with phenobarbital or that had unacceptable adverse effects when treated with phenobarbital. PROCEDURES: Cats were treated with levetiracetam (20 mg/kg [9.1 mg/lb], PO, q 8 h). After a minimum of 1 week of treatment, serum levetiracetam concentrations were measured before and 2, 4, and 6 hours after drug administration, and maximum and minimum serum concentrations and elimination half-life were calculated. Seizure frequencies before and after initiation of levetiracetam treatment were compared, and adverse effects were recorded. RESULTS: Median maximum serum levetiracetam concentration was 25.5 microg/mL, median minimum serum levetiracetam concentration was 8.3 microg/mL, and median elimination half-life was 2.9 hours. Median seizure frequency prior to treatment with levetiracetam (2.1 seizures/mo) was significantly higher than median seizure frequency after initiation of levetiracetam treatment (0.42 seizures/mo), and 7 of 10 cats were classified as having responded to levetiracetam treatment (ie, reduction in seizure frequency of >or=50%). Two cats had transient lethargy and inappetence. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that levetiracetam is well tolerated in cats and may be useful as an adjunct to phenobarbital treatment in cats with idiopathic epilepsy.","[{'text': 'Levetiracetam', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'C026098'}, {'text': 'phenobarbital', 'type': 'Chemical', 'start': 31, 'end': 44, 'mesh': 'D010634'}, {'text': 'idiopathic epilepsy', 'type': 'Disease', 'start': 78, 'end': 97, 'mesh': 'C562694'}, {'text': 'levetiracetam', 'type': 'Chemical', 'start': 173, 'end': 186, 'mesh': 'C026098'}, {'text': 'phenobarbital', 'type': 'Chemical', 'start': 217, 'end': 230, 'mesh': 'D010634'}, {'text': 'idiopathic epilepsy', 'type': 'Disease', 'start': 282, 'end': 301, 'mesh': 'C562694'}, {'text': 'idiopathic epilepsy', 'type': 'Disease', 'start': 388, 'end': 407, 'mesh': 'C562694'}, {'text': 'phenobarbital', 'type': 'Chemical', 'start': 440, 'end': 453, 'mesh': 'D010634'}, {'text': 'phenobarbital', 'type': 'Chemical', 'start': 513, 'end': 526, 'mesh': 'D010634'}, {'text': 'levetiracetam', 'type': 'Chemical', 'start': 563, 'end': 576, 'mesh': 'C026098'}, {'text': 'levetiracetam', 'type': 'Chemical', 'start': 658, 'end': 671, 'mesh': 'C026098'}, {'text': 'Seizure', 'type': 'Disease', 'start': 845, 'end': 852, 'mesh': 'D012640'}, {'text': 'levetiracetam', 'type': 'Chemical', 'start': 896, 'end': 909, 'mesh': 'C026098'}, {'text': 'levetiracetam', 'type': 'Chemical', 'start': 1000, 'end': 1013, 'mesh': 'C026098'}, {'text': 'levetiracetam', 'type': 'Chemical', 'start': 1069, 'end': 1082, 'mesh': 'C026098'}, {'text': 'seizure', 'type': 'Disease', 'start': 1171, 'end': 1178, 'mesh': 'D012640'}, {'text': 'levetiracetam', 'type': 'Chemical', 'start': 1213, 'end': 1226, 'mesh': 'C026098'}, {'text': 'seizures', 'type': 'Disease', 'start': 1232, 'end': 1240, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 1282, 'end': 1289, 'mesh': 'D012640'}, {'text': 'levetiracetam', 'type': 'Chemical', 'start': 1320, 'end': 1333, 'mesh': 'C026098'}, {'text': 'seizures', 'type': 'Disease', 'start': 1350, 'end': 1358, 'mesh': 'D012640'}, {'text': 'levetiracetam', 'type': 'Chemical', 'start': 1420, 'end': 1433, 'mesh': 'C026098'}, {'text': 'seizure', 'type': 'Disease', 'start': 1462, 'end': 1469, 'mesh': 'D012640'}, {'text': 'lethargy', 'type': 'Disease', 'start': 1516, 'end': 1524, 'mesh': 'D053609'}, {'text': 'inappetence', 'type': 'Disease', 'start': 1529, 'end': 1540, 'mesh': '-1'}, {'text': 'levetiracetam', 'type': 'Chemical', 'start': 1601, 'end': 1614, 'mesh': 'C026098'}, {'text': 'phenobarbital', 'type': 'Chemical', 'start': 1676, 'end': 1689, 'mesh': 'D010634'}, {'text': 'idiopathic epilepsy', 'type': 'Disease', 'start': 1713, 'end': 1732, 'mesh': 'C562694'}]"
+1117,19681452,Bilateral haemorrhagic infarction of the globus pallidus after cocaine and alcohol intoxication.,"Cocaine is a risk factor for both ischemic and haemorrhagic stroke. We present the case of a 31-year-old man with bilateral ischemia of the globus pallidus after excessive alcohol and intranasal cocaine use. Drug-related globus pallidus infarctions are most often associated with heroin. Bilateral basal ganglia infarcts after the use of cocaine, without concurrent heroin use, have never been reported. In our patient, transient cardiac arrhythmia or respiratory dysfunction related to cocaine and/or ethanol use were the most likely causes of cerebral hypoperfusion.","[{'text': 'cocaine', 'type': 'Chemical', 'start': 63, 'end': 70, 'mesh': 'D003042'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 75, 'end': 82, 'mesh': 'D000431'}, {'text': 'Cocaine', 'type': 'Chemical', 'start': 97, 'end': 104, 'mesh': 'D003042'}, {'text': 'ischemia of the globus pallidus', 'type': 'Disease', 'start': 221, 'end': 252, 'mesh': 'D002545'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 269, 'end': 276, 'mesh': 'D000431'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 292, 'end': 299, 'mesh': 'D003042'}, {'text': 'globus pallidus infarctions', 'type': 'Disease', 'start': 318, 'end': 345, 'mesh': 'D020520'}, {'text': 'heroin', 'type': 'Chemical', 'start': 377, 'end': 383, 'mesh': 'D003932'}, {'text': 'basal ganglia infarcts', 'type': 'Disease', 'start': 395, 'end': 417, 'mesh': 'D020520'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 435, 'end': 442, 'mesh': 'D003042'}, {'text': 'heroin', 'type': 'Chemical', 'start': 463, 'end': 469, 'mesh': 'D003932'}, {'text': 'cardiac arrhythmia', 'type': 'Disease', 'start': 527, 'end': 545, 'mesh': 'D001145'}, {'text': 'respiratory dysfunction', 'type': 'Disease', 'start': 549, 'end': 572, 'mesh': 'D012131'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 584, 'end': 591, 'mesh': 'D003042'}, {'text': 'ethanol', 'type': 'Chemical', 'start': 599, 'end': 606, 'mesh': 'D000431'}, {'text': 'cerebral hypoperfusion', 'type': 'Disease', 'start': 642, 'end': 664, 'mesh': '-1'}]"
+1118,20009434,Acute renal failure after high-dose methotrexate therapy in a patient with ileostomy.,"High-dose methotrexate (HD-MTX) is an important treatment for Burkitt lymphoma, but can cause hepatic and renal toxicity when its clearance is delayed. We report a case of acute renal failure after HD-MTX therapy in a patient with ileostomy, The patient was a 3-year-old boy who had received a living-related liver transplantation for congenital biliary atresia. At day 833 after the transplantation, he was diagnosed with PTLD (post-transplantation lymphoproliferative disorder, Burkitt-type malignant lymphoma). During induction therapy, he suffered ileal perforation and ileostomy was performed. Subsequent HD-MTX therapy caused acute renal failure that required continuous hemodialysis. We supposed that intravascular hypovolemia due to substantial drainage from the ileostoma caused acute prerenal failure. After recovery of his renal function, we could safely treat the patient with HD-MTX therapy by controlling drainage from ileostoma with total parenteral nutrition.","[{'text': 'Acute renal failure', 'type': 'Disease', 'start': 0, 'end': 19, 'mesh': 'D058186'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 36, 'end': 48, 'mesh': 'D008727'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 96, 'end': 108, 'mesh': 'D008727'}, {'text': 'MTX', 'type': 'Chemical', 'start': 113, 'end': 116, 'mesh': 'D008727'}, {'text': 'Burkitt lymphoma', 'type': 'Disease', 'start': 148, 'end': 164, 'mesh': 'D002051'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 258, 'end': 277, 'mesh': 'D058186'}, {'text': 'MTX', 'type': 'Chemical', 'start': 287, 'end': 290, 'mesh': 'D008727'}, {'text': 'biliary atresia', 'type': 'Disease', 'start': 432, 'end': 447, 'mesh': 'D001656'}, {'text': 'PTLD', 'type': 'Disease', 'start': 509, 'end': 513, 'mesh': 'D008232'}, {'text': 'post-transplantation lymphoproliferative disorder', 'type': 'Disease', 'start': 515, 'end': 564, 'mesh': 'D008232'}, {'text': 'Burkitt-type malignant lymphoma', 'type': 'Disease', 'start': 566, 'end': 597, 'mesh': 'D002051'}, {'text': 'MTX', 'type': 'Chemical', 'start': 699, 'end': 702, 'mesh': 'D008727'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 718, 'end': 737, 'mesh': 'D058186'}, {'text': 'hypovolemia', 'type': 'Disease', 'start': 808, 'end': 819, 'mesh': 'D020896'}, {'text': 'acute prerenal failure', 'type': 'Disease', 'start': 874, 'end': 896, 'mesh': '-1'}, {'text': 'MTX', 'type': 'Chemical', 'start': 978, 'end': 981, 'mesh': 'D008727'}]"
+1119,20431083,"Antithrombotic drug use, cerebral microbleeds, and intracerebral hemorrhage: a systematic review of published and unpublished studies.","BACKGROUND AND PURPOSE: Cerebral microbleeds (MB) are potential risk factors for intracerebral hemorrhage (ICH), but it is unclear if they are a contraindication to using antithrombotic drugs. Insights could be gained by pooling data on MB frequency stratified by antithrombotic use in cohorts with ICH and ischemic stroke (IS)/transient ischemic attack (TIA). METHODS: We performed a systematic review of published and unpublished data from cohorts with stroke or TIA to compare the presence of MB in: (1) antithrombotic users vs nonantithrombotic users with ICH; (2) antithrombotic users vs nonusers with IS/TIA; and (3) ICH vs ischemic events stratified by antithrombotic use. We also analyzed published and unpublished follow-up data to determine the risk of ICH in antithrombotic users with MB. RESULTS: In a pooled analysis of 1460 ICH and 3817 IS/TIA, MB were more frequent in ICH vs IS/TIA in all treatment groups, but the excess increased from 2.8 (odds ratio; range, 2.3-3.5) in nonantithrombotic users to 5.7 (range, 3.4-9.7) in antiplatelet users and 8.0 (range, 3.5-17.8) in warfarin users (P difference=0.01). There was also an excess of MB in warfarin users vs nonusers with ICH (OR, 2.7; 95% CI, 1.6-4.4; P<0.001) but none in warfarin users with IS/TIA (OR, 1.3; 95% CI, 0.9-1.7; P=0.33; P difference=0.01). There was a smaller excess of MB in antiplatelet users vs nonusers with ICH (OR, 1.7; 95% CI, 1.3-2.3; P<0.001), but findings were similar for antiplatelet users with IS/TIA (OR, 1.4; 95% CI, 1.2-1.7; P<0.001; P difference=0.25). In pooled follow-up data for 768 antithrombotic users, presence of MB at baseline was associated with a substantially increased risk of subsequent ICH (OR, 12.1; 95% CI, 3.4-42.5; P<0.001). CONCLUSIONS: The excess of MB in warfarin users with ICH compared to other groups suggests that MB increase the risk of warfarin-associated ICH. Limited prospective data corroborate these findings, but larger prospective studies are urgently required.","[{'text': 'cerebral microbleeds', 'type': 'Disease', 'start': 25, 'end': 45, 'mesh': '-1'}, {'text': 'intracerebral hemorrhage', 'type': 'Disease', 'start': 51, 'end': 75, 'mesh': 'D002543'}, {'text': 'Cerebral microbleeds', 'type': 'Disease', 'start': 159, 'end': 179, 'mesh': '-1'}, {'text': 'MB', 'type': 'Disease', 'start': 181, 'end': 183, 'mesh': '-1'}, {'text': 'intracerebral hemorrhage', 'type': 'Disease', 'start': 216, 'end': 240, 'mesh': 'D002543'}, {'text': 'ICH', 'type': 'Disease', 'start': 242, 'end': 245, 'mesh': 'D002543'}, {'text': 'MB', 'type': 'Disease', 'start': 372, 'end': 374, 'mesh': '-1'}, {'text': 'ICH', 'type': 'Disease', 'start': 434, 'end': 437, 'mesh': 'D002543'}, {'text': 'ischemic stroke', 'type': 'Disease', 'start': 442, 'end': 457, 'mesh': 'D002544'}, {'text': 'IS', 'type': 'Disease', 'start': 459, 'end': 461, 'mesh': 'D002544'}, {'text': 'transient ischemic attack', 'type': 'Disease', 'start': 463, 'end': 488, 'mesh': 'D002546'}, {'text': 'TIA', 'type': 'Disease', 'start': 490, 'end': 493, 'mesh': 'D002546'}, {'text': 'stroke', 'type': 'Disease', 'start': 590, 'end': 596, 'mesh': 'D020521'}, {'text': 'TIA', 'type': 'Disease', 'start': 600, 'end': 603, 'mesh': 'D002546'}, {'text': 'MB', 'type': 'Disease', 'start': 631, 'end': 633, 'mesh': '-1'}, {'text': 'ICH', 'type': 'Disease', 'start': 695, 'end': 698, 'mesh': 'D002543'}, {'text': 'IS', 'type': 'Disease', 'start': 742, 'end': 744, 'mesh': 'D002544'}, {'text': 'TIA', 'type': 'Disease', 'start': 745, 'end': 748, 'mesh': 'D002546'}, {'text': 'ICH', 'type': 'Disease', 'start': 758, 'end': 761, 'mesh': 'D002543'}, {'text': 'ischemic', 'type': 'Disease', 'start': 765, 'end': 773, 'mesh': 'D007511'}, {'text': 'ICH', 'type': 'Disease', 'start': 898, 'end': 901, 'mesh': 'D002543'}, {'text': 'MB', 'type': 'Disease', 'start': 931, 'end': 933, 'mesh': '-1'}, {'text': 'ICH', 'type': 'Disease', 'start': 973, 'end': 976, 'mesh': 'D002543'}, {'text': 'IS', 'type': 'Disease', 'start': 986, 'end': 988, 'mesh': 'D002544'}, {'text': 'TIA', 'type': 'Disease', 'start': 989, 'end': 992, 'mesh': 'D002546'}, {'text': 'MB', 'type': 'Disease', 'start': 994, 'end': 996, 'mesh': '-1'}, {'text': 'ICH', 'type': 'Disease', 'start': 1019, 'end': 1022, 'mesh': 'D002543'}, {'text': 'IS', 'type': 'Disease', 'start': 1026, 'end': 1028, 'mesh': 'D002544'}, {'text': 'TIA', 'type': 'Disease', 'start': 1029, 'end': 1032, 'mesh': 'D002546'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 1223, 'end': 1231, 'mesh': 'D014859'}, {'text': 'MB', 'type': 'Disease', 'start': 1287, 'end': 1289, 'mesh': '-1'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 1293, 'end': 1301, 'mesh': 'D014859'}, {'text': 'ICH', 'type': 'Disease', 'start': 1325, 'end': 1328, 'mesh': 'D002543'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 1377, 'end': 1385, 'mesh': 'D014859'}, {'text': 'IS', 'type': 'Disease', 'start': 1397, 'end': 1399, 'mesh': 'D002544'}, {'text': 'TIA', 'type': 'Disease', 'start': 1400, 'end': 1403, 'mesh': 'D002546'}, {'text': 'MB', 'type': 'Disease', 'start': 1489, 'end': 1491, 'mesh': '-1'}, {'text': 'ICH', 'type': 'Disease', 'start': 1531, 'end': 1534, 'mesh': 'D002543'}, {'text': 'IS', 'type': 'Disease', 'start': 1626, 'end': 1628, 'mesh': 'D002544'}, {'text': 'TIA', 'type': 'Disease', 'start': 1629, 'end': 1632, 'mesh': 'D002546'}, {'text': 'MB', 'type': 'Disease', 'start': 1756, 'end': 1758, 'mesh': '-1'}, {'text': 'ICH', 'type': 'Disease', 'start': 1836, 'end': 1839, 'mesh': 'D002543'}, {'text': 'MB', 'type': 'Disease', 'start': 1906, 'end': 1908, 'mesh': '-1'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 1912, 'end': 1920, 'mesh': 'D014859'}, {'text': 'ICH', 'type': 'Disease', 'start': 1932, 'end': 1935, 'mesh': 'D002543'}, {'text': 'MB', 'type': 'Disease', 'start': 1975, 'end': 1977, 'mesh': '-1'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 1999, 'end': 2007, 'mesh': 'D014859'}, {'text': 'ICH', 'type': 'Disease', 'start': 2019, 'end': 2022, 'mesh': 'D002543'}]"
+1120,20595935,Verapamil stimulation test in hyperprolactinemia: loss of prolactin response in anatomic or functional stalk effect.,"AIM: Verapamil stimulation test was previously investigated as a tool for differential diagnosis of hyperprolactinemia, but with conflicting results. Macroprolactinemia was never considered in those previous studies. Here, we aimed to re-investigate the diagnostic value of verapamil in a population who were all screened for macroprolactinemia. Prolactin responses to verapamil in 65 female patients (age: 29.9 +/- 8.1 years) with hyperprolactinemia were tested in a descriptive, matched case-control study. METHODS: Verapamil 80 mg, p.o. was administered, and then PRL levels were measured at 8th and 16th hours, by immunometric chemiluminescence. Verapamil responsiveness was determined by peak percent change in basal prolactin levels (PRL). RESULTS: Verapamil significantly increased PRL levels in healthy controls (N. 8, PRL: 183%), macroprolactinoma (N. 8, PRL: 7%), microprolactinoma (N. 19, PRL: 21%), macroprolactinemia (N. 23, PRL: 126%), but not in pseudoprolactinoma (N. 8, PRL: 0.8%), and risperidone-induced hyperprolactinemia (N. 7, PRL: 3%). ROC curve analysis revealed that unresponsiveness to verapamil defined as PRL <7%, discriminated anatomical or functional stalk effect (sensitivity: 74%, specificity: 73%, AUC: 0.855+/-0.04, P <0.001, CI: 0.768-0.942) associated with pseudoprolactinoma or risperidone-induced hyperprolactinemia, respectively. CONCLUSION: Verapamil responsiveness is not a reliable finding for the differential diagnosis of hyperprolactinemia. However, verapamil unresponsiveness discriminates stalk effect (i.e., anatomically or functionally inhibited dopaminergic tonus) from other causes of hyperprolactinemia with varying degrees of responsiveness.","[{'text': 'Verapamil', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D014700'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 30, 'end': 48, 'mesh': 'D006966'}, {'text': 'Verapamil', 'type': 'Chemical', 'start': 122, 'end': 131, 'mesh': 'D014700'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 217, 'end': 235, 'mesh': 'D006966'}, {'text': 'Macroprolactinemia', 'type': 'Disease', 'start': 267, 'end': 285, 'mesh': 'D015175'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 391, 'end': 400, 'mesh': 'D014700'}, {'text': 'macroprolactinemia', 'type': 'Disease', 'start': 443, 'end': 461, 'mesh': 'D015175'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 486, 'end': 495, 'mesh': 'D014700'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 549, 'end': 567, 'mesh': 'D006966'}, {'text': 'Verapamil', 'type': 'Chemical', 'start': 635, 'end': 644, 'mesh': 'D014700'}, {'text': 'Verapamil', 'type': 'Chemical', 'start': 767, 'end': 776, 'mesh': 'D014700'}, {'text': 'Verapamil', 'type': 'Chemical', 'start': 872, 'end': 881, 'mesh': 'D014700'}, {'text': 'macroprolactinoma', 'type': 'Disease', 'start': 956, 'end': 973, 'mesh': 'D015175'}, {'text': 'microprolactinoma', 'type': 'Disease', 'start': 991, 'end': 1008, 'mesh': 'D015175'}, {'text': 'macroprolactinemia', 'type': 'Disease', 'start': 1028, 'end': 1046, 'mesh': 'D015175'}, {'text': 'pseudoprolactinoma', 'type': 'Disease', 'start': 1078, 'end': 1096, 'mesh': '-1'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 1120, 'end': 1131, 'mesh': 'D018967'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 1140, 'end': 1158, 'mesh': 'D006966'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 1229, 'end': 1238, 'mesh': 'D014700'}, {'text': 'pseudoprolactinoma', 'type': 'Disease', 'start': 1410, 'end': 1428, 'mesh': '-1'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 1432, 'end': 1443, 'mesh': 'D018967'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 1452, 'end': 1470, 'mesh': 'D006966'}, {'text': 'Verapamil', 'type': 'Chemical', 'start': 1498, 'end': 1507, 'mesh': 'D014700'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 1583, 'end': 1601, 'mesh': 'D006966'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 1612, 'end': 1621, 'mesh': 'D014700'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 1753, 'end': 1771, 'mesh': 'D006966'}]"
+1121,35781,Central action of narcotic analgesics. Part IV. Noradrenergic influences on the activity of analgesics in rats.,"The effect of clonidine, naphazoline and xylometazoline on analgesia induced by morphine, codeine, fentanyl and pentazocine, and on cataleptic effect of morphine, codine and fentanyl was studied in rats. The biochemical assays on the influence of four analgesics on the brain concentration and turnover of noradrenaline (NA) were also performed. It was found that three drugs stimulating central NA receptors failed to affect the analgesic ED50 of all antinociceptive agents and they enhanced catalepsy induced by morphine and fentanyl. Codeine catalepsy was increased by clonidine and decreased by naphazoline and xylometazoline. The brain concentration of NA was not changed by morphine and fentanyl, but one of the doses of codeine (45 mg/kg) slightly enhanced it. Pentazocine dose-dependently decreased the brain level of NA. The rate of NA turnover was not altered by analgesics except for the higher dose of fentanyl (0.2 mg/kg) following which the disappearance of NA from the brain was diminished. The results are discussed in the light of various and non-uniform data from the literature. It is suggested that in rats the brain NA plays a less important function than the other monoamines in the behavioural activity of potent analgesics.","[{'text': 'clonidine', 'type': 'Chemical', 'start': 126, 'end': 135, 'mesh': 'D003000'}, {'text': 'naphazoline', 'type': 'Chemical', 'start': 137, 'end': 148, 'mesh': 'D009278'}, {'text': 'xylometazoline', 'type': 'Chemical', 'start': 153, 'end': 167, 'mesh': 'C009695'}, {'text': 'morphine', 'type': 'Chemical', 'start': 192, 'end': 200, 'mesh': 'D009020'}, {'text': 'codeine', 'type': 'Chemical', 'start': 202, 'end': 209, 'mesh': 'D003061'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 211, 'end': 219, 'mesh': 'D005283'}, {'text': 'pentazocine', 'type': 'Chemical', 'start': 224, 'end': 235, 'mesh': 'D010423'}, {'text': 'cataleptic', 'type': 'Disease', 'start': 244, 'end': 254, 'mesh': 'D002375'}, {'text': 'morphine', 'type': 'Chemical', 'start': 265, 'end': 273, 'mesh': 'D009020'}, {'text': 'codine', 'type': 'Chemical', 'start': 275, 'end': 281, 'mesh': 'D003061'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 286, 'end': 294, 'mesh': 'D005283'}, {'text': 'noradrenaline', 'type': 'Chemical', 'start': 418, 'end': 431, 'mesh': 'D009638'}, {'text': 'NA', 'type': 'Chemical', 'start': 433, 'end': 435, 'mesh': 'D009638'}, {'text': 'NA', 'type': 'Chemical', 'start': 508, 'end': 510, 'mesh': 'D009638'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 605, 'end': 614, 'mesh': 'D002375'}, {'text': 'morphine', 'type': 'Chemical', 'start': 626, 'end': 634, 'mesh': 'D009020'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 639, 'end': 647, 'mesh': 'D005283'}, {'text': 'Codeine', 'type': 'Chemical', 'start': 649, 'end': 656, 'mesh': 'D003061'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 657, 'end': 666, 'mesh': 'D002375'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 684, 'end': 693, 'mesh': 'D003000'}, {'text': 'naphazoline', 'type': 'Chemical', 'start': 711, 'end': 722, 'mesh': 'D009278'}, {'text': 'xylometazoline', 'type': 'Chemical', 'start': 727, 'end': 741, 'mesh': 'C009695'}, {'text': 'NA', 'type': 'Chemical', 'start': 770, 'end': 772, 'mesh': 'D009638'}, {'text': 'morphine', 'type': 'Chemical', 'start': 792, 'end': 800, 'mesh': 'D009020'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 805, 'end': 813, 'mesh': 'D005283'}, {'text': 'codeine', 'type': 'Chemical', 'start': 839, 'end': 846, 'mesh': 'D003061'}, {'text': 'Pentazocine', 'type': 'Chemical', 'start': 880, 'end': 891, 'mesh': 'D010423'}, {'text': 'NA', 'type': 'Chemical', 'start': 938, 'end': 940, 'mesh': 'D009638'}, {'text': 'NA', 'type': 'Chemical', 'start': 954, 'end': 956, 'mesh': 'D009638'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 1026, 'end': 1034, 'mesh': 'D005283'}, {'text': 'NA', 'type': 'Chemical', 'start': 1084, 'end': 1086, 'mesh': 'D009638'}, {'text': 'NA', 'type': 'Chemical', 'start': 1249, 'end': 1251, 'mesh': 'D009638'}, {'text': 'monoamines', 'type': 'Chemical', 'start': 1299, 'end': 1309, 'mesh': 'D015306'}]"
+1122,48835,Modification by propranolol of cardiovascular effects of induced hypoglycaemia.,"The cardiovascular effects of hypoglycaemia, with and without beta-blockade, were compared in fourteen healthy men. Eight received insulin alone, and eight, including two of the original insulin-only group, were given propranolol and insulin. In the insulin-group the period of hypoglycaemia was associated with an increase in heart-rate and a fall in diastolic blood-pressure. In the propranolol-insulin group there was a significant fall in heart-rate in most subjects and an increase in diastolic pressure. Typical S-T/T changes occurred in the insulin-group but in none of the propranolol-insulin group. Hypertension in diabetics prone to hypoglycaemia attacks should not be treated with beta-blockers because these drugs may cause a sharp rise in blood-pressure in such patients.","[{'text': 'propranolol', 'type': 'Chemical', 'start': 16, 'end': 27, 'mesh': 'D011433'}, {'text': 'hypoglycaemia', 'type': 'Disease', 'start': 65, 'end': 78, 'mesh': 'D007003'}, {'text': 'hypoglycaemia', 'type': 'Disease', 'start': 110, 'end': 123, 'mesh': 'D007003'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 298, 'end': 309, 'mesh': 'D011433'}, {'text': 'hypoglycaemia', 'type': 'Disease', 'start': 358, 'end': 371, 'mesh': 'D007003'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 465, 'end': 476, 'mesh': 'D011433'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 661, 'end': 672, 'mesh': 'D011433'}, {'text': 'Hypertension', 'type': 'Disease', 'start': 688, 'end': 700, 'mesh': 'D006973'}, {'text': 'diabetics', 'type': 'Disease', 'start': 704, 'end': 713, 'mesh': 'D003920'}, {'text': 'hypoglycaemia', 'type': 'Disease', 'start': 723, 'end': 736, 'mesh': 'D007003'}]"
+1123,89511,Prevention and treatment of endometrial disease in climacteric women receiving oestrogen therapy.,The treatment regimens are described in 74 patients with endometrial disease among 850 climacteric women receiving oestrogen therapy. Cystic hyperplasia was associated with unopposed oestrogen therapy without progestagen. Two courses of 21 days of 5 mg norethisterone daily caused reversion to normal in all 57 cases of cystic hyperplasia and 6 of the 8 cases of atypical hyperplasia. 4 cases of endometrial carcinoma referred from elsewhere demonstrated the problems of inappropriate and unsupervised unopposed oestrogen therapy and the difficulty in distinguishing severe hyperplasia from malignancy. Cyclical low-dose oestrogen therapy with 7--13 days of progestagen does not seem to increase the risk of endometrial hyperplasia or carcinoma.,"[{'text': 'endometrial disease', 'type': 'Disease', 'start': 28, 'end': 47, 'mesh': 'D014591'}, {'text': 'oestrogen', 'type': 'Chemical', 'start': 79, 'end': 88, 'mesh': 'D004967'}, {'text': 'endometrial disease', 'type': 'Disease', 'start': 155, 'end': 174, 'mesh': 'D014591'}, {'text': 'oestrogen', 'type': 'Chemical', 'start': 213, 'end': 222, 'mesh': 'D004967'}, {'text': 'hyperplasia', 'type': 'Disease', 'start': 239, 'end': 250, 'mesh': 'D006965'}, {'text': 'oestrogen', 'type': 'Chemical', 'start': 281, 'end': 290, 'mesh': 'D004967'}, {'text': 'progestagen', 'type': 'Chemical', 'start': 307, 'end': 318, 'mesh': 'D011372'}, {'text': 'norethisterone', 'type': 'Chemical', 'start': 351, 'end': 365, 'mesh': 'D009640'}, {'text': 'hyperplasia', 'type': 'Disease', 'start': 425, 'end': 436, 'mesh': 'D006965'}, {'text': 'hyperplasia', 'type': 'Disease', 'start': 470, 'end': 481, 'mesh': 'D006965'}, {'text': 'endometrial carcinoma', 'type': 'Disease', 'start': 494, 'end': 515, 'mesh': 'D016889'}, {'text': 'oestrogen', 'type': 'Chemical', 'start': 610, 'end': 619, 'mesh': 'D004967'}, {'text': 'hyperplasia', 'type': 'Disease', 'start': 672, 'end': 683, 'mesh': 'D006965'}, {'text': 'malignancy', 'type': 'Disease', 'start': 689, 'end': 699, 'mesh': 'D009369'}, {'text': 'oestrogen', 'type': 'Chemical', 'start': 719, 'end': 728, 'mesh': 'D004967'}, {'text': 'progestagen', 'type': 'Chemical', 'start': 756, 'end': 767, 'mesh': 'D011372'}, {'text': 'endometrial hyperplasia', 'type': 'Disease', 'start': 806, 'end': 829, 'mesh': 'D004714'}, {'text': 'carcinoma', 'type': 'Disease', 'start': 833, 'end': 842, 'mesh': 'D002277'}]"
+1124,146391,"Pure red cell aplasia, toxic dermatitis and lymphadenopathy in a patient taking diphenylhydantoin.","A patient taking diphenylhydantoin for 3 weeks developed a generalized skin rash, lymphadenopathy and pure red cell aplasia. After withdrawal of the pharmacon all symptoms disappeared spontaneously. Skin rash is a well-known complication of diphenylhydantoin treatment as is benign and malignant lymphadenopathy. Pure red cell aplasia associated with diphenylhydantoin medication has been reported in 3 patients. The exact mechanism by which diphenylhydantoin exerts its toxic effects is not known. In this patient the time relation between the ingestion of diphenylhydantoin and the occurrence of the skin rash, lymphadenopathy and pure red cell aplasia is very suggestive of a direct connection.","[{'text': 'Pure red cell aplasia', 'type': 'Disease', 'start': 0, 'end': 21, 'mesh': 'D012010'}, {'text': 'toxic dermatitis', 'type': 'Disease', 'start': 23, 'end': 39, 'mesh': 'D003875'}, {'text': 'lymphadenopathy', 'type': 'Disease', 'start': 44, 'end': 59, 'mesh': 'D008206'}, {'text': 'diphenylhydantoin', 'type': 'Chemical', 'start': 80, 'end': 97, 'mesh': 'D010672'}, {'text': 'diphenylhydantoin', 'type': 'Chemical', 'start': 116, 'end': 133, 'mesh': 'D010672'}, {'text': 'skin rash', 'type': 'Disease', 'start': 170, 'end': 179, 'mesh': 'D005076'}, {'text': 'lymphadenopathy', 'type': 'Disease', 'start': 181, 'end': 196, 'mesh': 'D008206'}, {'text': 'pure red cell aplasia', 'type': 'Disease', 'start': 201, 'end': 222, 'mesh': 'D012010'}, {'text': 'Skin rash', 'type': 'Disease', 'start': 298, 'end': 307, 'mesh': 'D005076'}, {'text': 'diphenylhydantoin', 'type': 'Chemical', 'start': 340, 'end': 357, 'mesh': 'D010672'}, {'text': 'lymphadenopathy', 'type': 'Disease', 'start': 395, 'end': 410, 'mesh': 'D008206'}, {'text': 'Pure red cell aplasia', 'type': 'Disease', 'start': 412, 'end': 433, 'mesh': 'D012010'}, {'text': 'diphenylhydantoin', 'type': 'Chemical', 'start': 450, 'end': 467, 'mesh': 'D010672'}, {'text': 'diphenylhydantoin', 'type': 'Chemical', 'start': 541, 'end': 558, 'mesh': 'D010672'}, {'text': 'diphenylhydantoin', 'type': 'Chemical', 'start': 657, 'end': 674, 'mesh': 'D010672'}, {'text': 'skin rash', 'type': 'Disease', 'start': 701, 'end': 710, 'mesh': 'D005076'}, {'text': 'lymphadenopathy', 'type': 'Disease', 'start': 712, 'end': 727, 'mesh': 'D008206'}, {'text': 'pure red cell aplasia', 'type': 'Disease', 'start': 732, 'end': 753, 'mesh': 'D012010'}]"
+1125,256433,Continuous infusion tobramycin combined with carbenicillin for infections in cancer patients.,"The cure rate of infections in cancer patients is adversely affected by neutropenia (less than 1,000/mm3). In particular, patients with severe neutropenia (less than 100/mm3) have shown a poor response to antibiotics. To overcome the adverse effects of neutropenia, tobramycin was given by continuous infusion and combined with intermittent carbenicillin. Tobramycin was given to a total daily dose of 300 mg/m2 and carbenicillin was given at a dose of 5 gm every four hours. There were 125 infectious episodes in 116 cancer patients receiving myelosuppressive chemotherapy. The overall cure rate was 70%. Pneumonia was the most common infection and 61% of 59 episodes were cured. Gram-negative bacilli were the most common causative organisms and 69% of these infections were cured. The most common pathogen was Klebsiella pneumoniae and this, together with Escherichia coli and Pseudomonas aeruginosa, accounted for 74% of all gram-negative bacillary infections. Response was not influenced by the initial neutrophil count, with a 62% cure rate for 39 episodes associated with severe neutropenia. However, failure of the neutrophil count to increase during therapy adversely affected response. Azotemia was the major side effect recognized, and it occurred in 11% of episodes. Major azotemia (serum creatinine greater than 2.5 mg/dl or BUN greater than 50 mg/dl) occurred in only 2%. Azotemia was not related to duration of therapy or serum tobramycin concentration. This antibiotic regimen showed both therapeutic efficacy and acceptable renal toxicity for these patients.","[{'text': 'tobramycin', 'type': 'Chemical', 'start': 20, 'end': 30, 'mesh': 'D014031'}, {'text': 'carbenicillin', 'type': 'Chemical', 'start': 45, 'end': 58, 'mesh': 'D002228'}, {'text': 'infections', 'type': 'Disease', 'start': 63, 'end': 73, 'mesh': 'D007239'}, {'text': 'cancer', 'type': 'Disease', 'start': 77, 'end': 83, 'mesh': 'D009369'}, {'text': 'infections', 'type': 'Disease', 'start': 111, 'end': 121, 'mesh': 'D007239'}, {'text': 'cancer', 'type': 'Disease', 'start': 125, 'end': 131, 'mesh': 'D009369'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 166, 'end': 177, 'mesh': 'D009503'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 237, 'end': 248, 'mesh': 'D009503'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 347, 'end': 358, 'mesh': 'D009503'}, {'text': 'tobramycin', 'type': 'Chemical', 'start': 360, 'end': 370, 'mesh': 'D014031'}, {'text': 'carbenicillin', 'type': 'Chemical', 'start': 435, 'end': 448, 'mesh': 'D002228'}, {'text': 'Tobramycin', 'type': 'Chemical', 'start': 450, 'end': 460, 'mesh': 'D014031'}, {'text': 'carbenicillin', 'type': 'Chemical', 'start': 510, 'end': 523, 'mesh': 'D002228'}, {'text': 'cancer', 'type': 'Disease', 'start': 612, 'end': 618, 'mesh': 'D009369'}, {'text': 'Pneumonia', 'type': 'Disease', 'start': 700, 'end': 709, 'mesh': 'D011014'}, {'text': 'infection', 'type': 'Disease', 'start': 730, 'end': 739, 'mesh': 'D007239'}, {'text': 'infections', 'type': 'Disease', 'start': 855, 'end': 865, 'mesh': 'D007239'}, {'text': 'pneumoniae', 'type': 'Disease', 'start': 918, 'end': 928, 'mesh': 'D011014'}, {'text': 'gram-negative bacillary infections', 'type': 'Disease', 'start': 1023, 'end': 1057, 'mesh': 'D016905'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 1180, 'end': 1191, 'mesh': 'D009503'}, {'text': 'Azotemia', 'type': 'Disease', 'start': 1290, 'end': 1298, 'mesh': 'D053099'}, {'text': 'azotemia', 'type': 'Disease', 'start': 1379, 'end': 1387, 'mesh': 'D053099'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1395, 'end': 1405, 'mesh': 'D003404'}, {'text': 'Azotemia', 'type': 'Disease', 'start': 1480, 'end': 1488, 'mesh': 'D053099'}, {'text': 'tobramycin', 'type': 'Chemical', 'start': 1537, 'end': 1547, 'mesh': 'D014031'}, {'text': 'renal toxicity', 'type': 'Disease', 'start': 1635, 'end': 1649, 'mesh': 'D007674'}]"
+1126,448423,Recurrent subarachnoid hemorrhage associated with aminocaproic acid therapy and acute renal artery thrombosis. Case report.,"Epsilon aminocaproic acid (EACA) has been used to prevent rebleeding in patients with subarachnoid hemorrhage (SAH). Although this agent does decrease the frequency of rebleeding, several reports have described thrombotic complications of EACA therapy. These complications have included clinical deterioration and intracranial vascular thrombosis in patients with SAH, arteriolar and capillary fibrin thrombi in patients with fibrinolytic syndromes treated with EACA, or other thromboembolic phenomena. Since intravascular fibrin thrombi are often observed in patients with fibrinolytic disorders, EACA should not be implicated in the pathogenesis of fibrin thrombi in patients with disseminated intravascular coagulation or other ""consumption coagulopathies."" This report describes subtotal infarction of the kidney due to thrombosis of a normal renal artery. This occlusion occurred after EACA therapy in a patient with SAH and histopathological documentation of recurrent SAH. The corresponding clinical event was characterized by marked hypertension and abrupt neurological deterioration.","[{'text': 'subarachnoid hemorrhage', 'type': 'Disease', 'start': 10, 'end': 33, 'mesh': 'D013345'}, {'text': 'aminocaproic acid', 'type': 'Chemical', 'start': 50, 'end': 67, 'mesh': 'D000614'}, {'text': 'acute renal artery thrombosis', 'type': 'Disease', 'start': 80, 'end': 109, 'mesh': 'D007674'}, {'text': 'Epsilon aminocaproic acid', 'type': 'Chemical', 'start': 124, 'end': 149, 'mesh': 'D015119'}, {'text': 'EACA', 'type': 'Chemical', 'start': 151, 'end': 155, 'mesh': 'D015119'}, {'text': 'subarachnoid hemorrhage', 'type': 'Disease', 'start': 210, 'end': 233, 'mesh': 'D013345'}, {'text': 'SAH', 'type': 'Disease', 'start': 235, 'end': 238, 'mesh': 'D013345'}, {'text': 'thrombotic', 'type': 'Disease', 'start': 335, 'end': 345, 'mesh': 'D013927'}, {'text': 'EACA', 'type': 'Chemical', 'start': 363, 'end': 367, 'mesh': 'D015119'}, {'text': 'intracranial vascular thrombosis', 'type': 'Disease', 'start': 438, 'end': 470, 'mesh': 'D020767'}, {'text': 'SAH', 'type': 'Disease', 'start': 488, 'end': 491, 'mesh': 'D013345'}, {'text': 'thrombi', 'type': 'Disease', 'start': 525, 'end': 532, 'mesh': 'D013927'}, {'text': 'EACA', 'type': 'Chemical', 'start': 586, 'end': 590, 'mesh': 'D015119'}, {'text': 'thromboembolic phenomena', 'type': 'Disease', 'start': 601, 'end': 625, 'mesh': 'D013923'}, {'text': 'thrombi', 'type': 'Disease', 'start': 654, 'end': 661, 'mesh': 'D013927'}, {'text': 'EACA', 'type': 'Chemical', 'start': 722, 'end': 726, 'mesh': 'D015119'}, {'text': 'thrombi', 'type': 'Disease', 'start': 782, 'end': 789, 'mesh': 'D013927'}, {'text': 'disseminated intravascular coagulation', 'type': 'Disease', 'start': 807, 'end': 845, 'mesh': 'D004211'}, {'text': 'consumption coagulopathies', 'type': 'Disease', 'start': 856, 'end': 882, 'mesh': 'D004211'}, {'text': 'infarction', 'type': 'Disease', 'start': 916, 'end': 926, 'mesh': 'D007238'}, {'text': 'thrombosis of a normal renal artery', 'type': 'Disease', 'start': 948, 'end': 983, 'mesh': 'D007674'}, {'text': 'EACA', 'type': 'Chemical', 'start': 1015, 'end': 1019, 'mesh': 'D015119'}, {'text': 'SAH', 'type': 'Disease', 'start': 1046, 'end': 1049, 'mesh': 'D013345'}, {'text': 'SAH', 'type': 'Disease', 'start': 1099, 'end': 1102, 'mesh': 'D013345'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1165, 'end': 1177, 'mesh': 'D006973'}]"
+1127,573555,Long-term propranolol therapy in pregnancy: maternal and fetal outcome.,"Propranolol, a beta-adrenergic blocking agent, has found an important position in the practice of medicine. Its use in pregnancy, however, is an open question as a number of detrimental side effects have been reported in the fetus and neonate. Ten patients and 12 pregnancies are reported where chronic propranolol has been administered. Five patients with serial pregnancies with and without propranolol therapy are also examined. Maternal, fetal, and neonatal complications are examined. An attempt is made to differentiate drug-related complications from maternal disease--related complications. We conclude that previously reported hypoglycemia, hyperbilirubinemia, polycythemia, neonatal apnea, and bradycardia are not invariable and cannot be statistically correlated with chronic propranolol therapy. Growth retardation, however, appears to be significant in both of our series.","[{'text': 'propranolol', 'type': 'Chemical', 'start': 10, 'end': 21, 'mesh': 'D011433'}, {'text': 'Propranolol', 'type': 'Chemical', 'start': 72, 'end': 83, 'mesh': 'D011433'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 375, 'end': 386, 'mesh': 'D011433'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 465, 'end': 476, 'mesh': 'D011433'}, {'text': 'hypoglycemia', 'type': 'Disease', 'start': 708, 'end': 720, 'mesh': 'D007003'}, {'text': 'hyperbilirubinemia', 'type': 'Disease', 'start': 722, 'end': 740, 'mesh': 'D006932'}, {'text': 'polycythemia', 'type': 'Disease', 'start': 742, 'end': 754, 'mesh': 'D011086'}, {'text': 'neonatal apnea', 'type': 'Disease', 'start': 756, 'end': 770, 'mesh': 'D001049'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 776, 'end': 787, 'mesh': 'D001919'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 859, 'end': 870, 'mesh': 'D011433'}, {'text': 'Growth retardation', 'type': 'Disease', 'start': 880, 'end': 898, 'mesh': 'D005317'}]"
+1128,611664,Use of propranolol in the treatment of idiopathic orthostatic hypotension.,"Five patients with idiopathic orthostatic hypotension who had physiologic and biochemical evidence of severe autonomic dysfunction were included in the study. They all exhibited markedly reduced plasma catecholamines and plasma renin activity in both recumbent and upright positions and had marked hypersensitivity to the pressor effects of infused norepinephrine. Treatment with propanolol administered intravenously (1-5 mg) produced increases in supine and upright blood pressure in 4 of the 5 individuals with rises ranging from 11/6 to 22/11 mmHg. Chronic oral administration of propranolol (40-160 mg/day) also elevated the blood pressures of these individuals with increases in the order of 20-35/15-25 mmg being observed. In 1 patient, marked hypertension was induced by propranolol and the drug had to be withdrawn. It otherwise was well tolerated and no important side effects were observed. Treatment has been continued in 3 individuals for 6-13 months with persistence of the pressor effect, although there appears to have been some decrease in the degree of response with time. Hemodynamic measurements in 1 of the patients demonstrated an increase in total peripheral resistance and essentially no change in cardiac output following propranolol therapy. The studies suggest that propranolol is a useful drug in selected patients with severe idiopathic orthostatic hypotension.","[{'text': 'propranolol', 'type': 'Chemical', 'start': 7, 'end': 18, 'mesh': 'D011433'}, {'text': 'idiopathic orthostatic hypotension', 'type': 'Disease', 'start': 39, 'end': 73, 'mesh': 'C544351'}, {'text': 'idiopathic orthostatic hypotension', 'type': 'Disease', 'start': 94, 'end': 128, 'mesh': 'C544351'}, {'text': 'catecholamines', 'type': 'Chemical', 'start': 277, 'end': 291, 'mesh': 'D002395'}, {'text': 'hypersensitivity', 'type': 'Disease', 'start': 373, 'end': 389, 'mesh': 'D004342'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 424, 'end': 438, 'mesh': 'D009638'}, {'text': 'propanolol', 'type': 'Chemical', 'start': 455, 'end': 465, 'mesh': 'D011433'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 659, 'end': 670, 'mesh': 'D011433'}, {'text': 'hypertension', 'type': 'Disease', 'start': 826, 'end': 838, 'mesh': 'D006973'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 854, 'end': 865, 'mesh': 'D011433'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 1322, 'end': 1333, 'mesh': 'D011433'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 1368, 'end': 1379, 'mesh': 'D011433'}, {'text': 'idiopathic orthostatic hypotension', 'type': 'Disease', 'start': 1430, 'end': 1464, 'mesh': 'C544351'}]"
+1129,612112,Total intravenous anesthesia with etomidate. III. Some observations in adults.,"An investigation was undertaken to determine the dosage of etomidate required to maintain sleep in adults undergoing surgery under regional local anesthesia. Premedication of diazepam 10 mg and atropine 0.5 mg was given, and sleep was induced and maintained by intermittent intravenous injections of etomidate 0.1/mg/kg, given whenever the patient would open his eyes on request. A mean overall dose of etomidate 17.4 microgram/kg/min. was required to maintain sleep, but great individual variation occurred, with older patients requiring less drug. The investigation was discontinued after 18 patients because of the frequency and intensity of side-effects, particularly pain and myoclonia, which caused the technique to be abandoned in two cases. It is considered unlikely that etomidate will prove to be the hypnotic of choice for a totally intravenous anesthetic technique in adults because of the high incidence of myoclonia after prolonged administration. In several patients uncontrollable muscle movements persisted for many minutes after complete recovery of consciousness.","[{'text': 'etomidate', 'type': 'Chemical', 'start': 34, 'end': 43, 'mesh': 'D005045'}, {'text': 'etomidate', 'type': 'Chemical', 'start': 138, 'end': 147, 'mesh': 'D005045'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 254, 'end': 262, 'mesh': 'D003975'}, {'text': 'atropine', 'type': 'Chemical', 'start': 273, 'end': 281, 'mesh': 'D001285'}, {'text': 'etomidate', 'type': 'Chemical', 'start': 379, 'end': 388, 'mesh': 'D005045'}, {'text': 'etomidate', 'type': 'Chemical', 'start': 482, 'end': 491, 'mesh': 'D005045'}, {'text': 'pain', 'type': 'Disease', 'start': 751, 'end': 755, 'mesh': 'D010146'}, {'text': 'myoclonia', 'type': 'Disease', 'start': 760, 'end': 769, 'mesh': 'D009207'}, {'text': 'etomidate', 'type': 'Chemical', 'start': 859, 'end': 868, 'mesh': 'D005045'}, {'text': 'myoclonia', 'type': 'Disease', 'start': 999, 'end': 1008, 'mesh': 'D009207'}]"
+1130,689020,"A method for the measurement of tremor, and a comparison of the effects of tocolytic beta-mimetics.","A method permitting measurement of finger tremor as a displacement-time curve is described, using a test system with simple amplitude calibration. The coordinates of the inversion points of the displacement-time curves were transferred through graphical input equipment to punched tape. By means of a computer program, periods and amplitudes of tremor oscillations were calculated and classified. The event frequency for each class of periods and amplitudes was determined. The actions of fenoterol-hydrobromide, ritodrin-HCl and placebo given to 10 healthy subjects by intravenous infusion in a double-blind crossover study were tested by this method. At therapeutic doses both substances raised the mean tremor amplitude to about three times the control level. At the same time, the mean period within each class of amplitudes shortened by 10--20 ms, whereas the mean periods calculated from all oscillations together did not change significantly. After the end of fenoterol-hydrobromide infusion, tremor amplitudes decreased significantly faster than those following ritodrin-HCl infusion.","[{'text': 'tremor', 'type': 'Disease', 'start': 32, 'end': 38, 'mesh': 'D014202'}, {'text': 'tremor', 'type': 'Disease', 'start': 142, 'end': 148, 'mesh': 'D014202'}, {'text': 'tremor', 'type': 'Disease', 'start': 445, 'end': 451, 'mesh': 'D014202'}, {'text': 'fenoterol-hydrobromide', 'type': 'Chemical', 'start': 589, 'end': 611, 'mesh': 'D005280'}, {'text': 'ritodrin-HCl', 'type': 'Chemical', 'start': 613, 'end': 625, 'mesh': 'D012312'}, {'text': 'tremor', 'type': 'Disease', 'start': 806, 'end': 812, 'mesh': 'D014202'}, {'text': 'fenoterol-hydrobromide', 'type': 'Chemical', 'start': 1067, 'end': 1089, 'mesh': 'D005280'}, {'text': 'tremor', 'type': 'Disease', 'start': 1100, 'end': 1106, 'mesh': 'D014202'}, {'text': 'ritodrin-HCl', 'type': 'Chemical', 'start': 1170, 'end': 1182, 'mesh': 'D012312'}]"
+1131,733189,Bilateral retinal artery and choriocapillaris occlusion following the injection of long-acting corticosteroid suspensions in combination with other drugs: I. Clinical studies.,"Two well-documented cases of bilateral retinal artery and choriocapillaris occlusions with blindness following head and neck soft-tissue injection with methylprednisolone acetate in combination with lidocaine, epinephrine, or penicillin are reported. One case had only a unilateral injection. The acute observations included hazy sensorium, superior gaze palsy, pupillary abnormalities, and conjunctival hemorrhages with edema. Follow-up changes showed marked visual loss, constricted visual fields, optic nerve pallor, vascular attenuation, and chorioretinal atrophy. The literature is reviewed, and possible causes are discussed.","[{'text': 'retinal artery and choriocapillaris occlusion', 'type': 'Disease', 'start': 10, 'end': 55, 'mesh': 'D015356'}, {'text': 'corticosteroid', 'type': 'Chemical', 'start': 95, 'end': 109, 'mesh': 'D000305'}, {'text': 'retinal artery and choriocapillaris occlusions', 'type': 'Disease', 'start': 215, 'end': 261, 'mesh': 'D015356'}, {'text': 'blindness', 'type': 'Disease', 'start': 267, 'end': 276, 'mesh': 'D001766'}, {'text': 'methylprednisolone acetate', 'type': 'Chemical', 'start': 328, 'end': 354, 'mesh': 'C000873'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 375, 'end': 384, 'mesh': 'D008012'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 386, 'end': 397, 'mesh': 'D004837'}, {'text': 'penicillin', 'type': 'Chemical', 'start': 402, 'end': 412, 'mesh': 'D010406'}, {'text': 'palsy', 'type': 'Disease', 'start': 531, 'end': 536, 'mesh': 'D010243'}, {'text': 'pupillary abnormalities', 'type': 'Disease', 'start': 538, 'end': 561, 'mesh': 'D011681'}, {'text': 'hemorrhages', 'type': 'Disease', 'start': 580, 'end': 591, 'mesh': 'D006470'}, {'text': 'edema', 'type': 'Disease', 'start': 597, 'end': 602, 'mesh': 'D004487'}, {'text': 'visual loss', 'type': 'Disease', 'start': 636, 'end': 647, 'mesh': 'D014786'}, {'text': 'chorioretinal atrophy', 'type': 'Disease', 'start': 722, 'end': 743, 'mesh': 'C566236'}]"
+1132,816141,Cephalothin-induced immune hemolytic anemia.,"A patient with renal disease developed Coombs-positive hemolytic anemia while receiving cephalothin therapy. An anti-cephalothin IgG antibody was detected in the patient's serum and in the eluates from her erythrocytes. In addition, nonimmunologic binding of normal and patient's serum proteins to her own and cephalothin-coated normal red cells was demonstrated. Skin tests and in vitro lymphocyte stimulation revealed that the patient was sensitized to cephalothin and also to ampicillin. Careful investigation of drug-induced hemolytic anemias reveals the complexity of the immune mechanisms involved.","[{'text': 'Cephalothin', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D002512'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 27, 'end': 43, 'mesh': 'D000743'}, {'text': 'renal disease', 'type': 'Disease', 'start': 60, 'end': 73, 'mesh': 'D007674'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 100, 'end': 116, 'mesh': 'D000743'}, {'text': 'cephalothin', 'type': 'Chemical', 'start': 133, 'end': 144, 'mesh': 'D002512'}, {'text': 'cephalothin', 'type': 'Chemical', 'start': 162, 'end': 173, 'mesh': 'D002512'}, {'text': 'cephalothin', 'type': 'Chemical', 'start': 355, 'end': 366, 'mesh': 'D002512'}, {'text': 'cephalothin', 'type': 'Chemical', 'start': 500, 'end': 511, 'mesh': 'D002512'}, {'text': 'ampicillin', 'type': 'Chemical', 'start': 524, 'end': 534, 'mesh': 'D000667'}, {'text': 'hemolytic anemias', 'type': 'Disease', 'start': 574, 'end': 591, 'mesh': 'D000743'}]"
+1133,851038,Kaliuretic effect of L-dopa treatment in parkinsonian patients.,"Hypokalemia, sometimes severe, was observed in some L-dopa-treated parkinsonian patients. The influence of L-dopa on the renal excretion of potassium was studied in 3 patients with hypokalemia and in 5 normokalemic patients by determination of renal plasma flow, glomerular filtration rate, plasma concentration of potassium and sodium as well as urinary excretion of potassium, sodium and aldosterone. L-Dopa intake was found to cause an increased excretion of potassium, and sometimes also of sodium, in the hypokalemic but not in the normokalemic patients. This effect on the renal function could be prohibited by the administration of a peripheral dopa decarbodylase inhibitor. It is not known why this effect occurred in some individuals but not in others, but our results indicate a correlation between aldosterone production and this renal effect of L-dopa.","[{'text': 'L-dopa', 'type': 'Chemical', 'start': 21, 'end': 27, 'mesh': 'D007980'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 41, 'end': 53, 'mesh': 'D010300'}, {'text': 'Hypokalemia', 'type': 'Disease', 'start': 64, 'end': 75, 'mesh': 'D007008'}, {'text': 'L-dopa', 'type': 'Chemical', 'start': 116, 'end': 122, 'mesh': 'D007980'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 131, 'end': 143, 'mesh': 'D010300'}, {'text': 'L-dopa', 'type': 'Chemical', 'start': 171, 'end': 177, 'mesh': 'D007980'}, {'text': 'potassium', 'type': 'Chemical', 'start': 204, 'end': 213, 'mesh': 'D011188'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 245, 'end': 256, 'mesh': 'D007008'}, {'text': 'potassium', 'type': 'Chemical', 'start': 379, 'end': 388, 'mesh': 'D011188'}, {'text': 'sodium', 'type': 'Chemical', 'start': 393, 'end': 399, 'mesh': 'D012964'}, {'text': 'potassium', 'type': 'Chemical', 'start': 432, 'end': 441, 'mesh': 'D011188'}, {'text': 'sodium', 'type': 'Chemical', 'start': 443, 'end': 449, 'mesh': 'D012964'}, {'text': 'aldosterone', 'type': 'Chemical', 'start': 454, 'end': 465, 'mesh': 'D000450'}, {'text': 'L-Dopa', 'type': 'Chemical', 'start': 467, 'end': 473, 'mesh': 'D007980'}, {'text': 'potassium', 'type': 'Chemical', 'start': 526, 'end': 535, 'mesh': 'D011188'}, {'text': 'sodium', 'type': 'Chemical', 'start': 559, 'end': 565, 'mesh': 'D012964'}, {'text': 'aldosterone', 'type': 'Chemical', 'start': 873, 'end': 884, 'mesh': 'D000450'}, {'text': 'L-dopa', 'type': 'Chemical', 'start': 921, 'end': 927, 'mesh': 'D007980'}]"
+1134,891494,Phenytoin encephalopathy as probable idiosyncratic reaction: case report.,"A case of phenytoin (DPH) encephalopathy with increasing seizures and EEG and mental changes is described. Despite adequate oral dosage of DPH (5 mg/kg/daily) the plasma level was very low (2.8 microgramg/ml). The encephalopathy was probably an idiosyncratic and not toxic or allergic reaction. In fact the concentration of free DPH was normal, the patient presented a retarded morbilliform rash during DPH treatment, the protidogram was normal, and an intradermic DPH injection had no local effect. The authors conclude that in a patient starting DPH treatment an unexpected increase in seizures, with EEG and mental changes occurring simultaneously, should alert the physician to the possible need for eliminating DPH from the therapeutic regimen, even if plasma concentrations are low.","[{'text': 'Phenytoin', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D010672'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 10, 'end': 24, 'mesh': 'D001927'}, {'text': 'phenytoin', 'type': 'Chemical', 'start': 84, 'end': 93, 'mesh': 'D010672'}, {'text': 'DPH', 'type': 'Chemical', 'start': 95, 'end': 98, 'mesh': 'D010672'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 100, 'end': 114, 'mesh': 'D001927'}, {'text': 'seizures', 'type': 'Disease', 'start': 131, 'end': 139, 'mesh': 'D012640'}, {'text': 'DPH', 'type': 'Chemical', 'start': 213, 'end': 216, 'mesh': 'D010672'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 288, 'end': 302, 'mesh': 'D001927'}, {'text': 'DPH', 'type': 'Chemical', 'start': 403, 'end': 406, 'mesh': 'D010672'}, {'text': 'rash', 'type': 'Disease', 'start': 465, 'end': 469, 'mesh': 'D005076'}, {'text': 'DPH', 'type': 'Chemical', 'start': 477, 'end': 480, 'mesh': 'D010672'}, {'text': 'DPH', 'type': 'Chemical', 'start': 539, 'end': 542, 'mesh': 'D010672'}, {'text': 'DPH', 'type': 'Chemical', 'start': 622, 'end': 625, 'mesh': 'D010672'}, {'text': 'seizures', 'type': 'Disease', 'start': 662, 'end': 670, 'mesh': 'D012640'}, {'text': 'DPH', 'type': 'Chemical', 'start': 790, 'end': 793, 'mesh': 'D010672'}]"
+1135,895432,Effects of exercise on the severity of isoproterenol-induced myocardial infarction.,"The effect of exercise on the severity of isoproterenol-induced myocardial infarction was studied in male rats. Ninety-three rats were randomly divided into three groups. The exercise-isoproterenol (E-1) and exercise control (EC) groups exercised daily for thirty days on a treadmill at 1 mph, 2% grade while animals of the sedentary-isoproterenol (S-I) group remained sedentary. Eight animals were assigned to the sedentary control (SC) group which remained sedentary throughout the experimental period. Forty-eight hours after the final exercise period, S-I and E-I animals received a single subcutaneous injection of isoproterenol (250 mg/kg body weight). Animals of the S-I group exhibited significantly (Pp less than 0.05) greater mortality from the effects of isoproterenol than animals of the E-I group. Serum CPK activity for E-I animals was significantly (p less than 0.05) greater than for animals in the S-I and EC groups twenty hours following isoproterenol injection. No statistically significant differences were observed between the two isoproterenol treated groups for severity of the induced lesions, changes in heart weight, or heart weight to body weight ratios. The results indicated that exercise reduced the mortality associated with the effects of large dosages of isoproterenol but had little on the severity of the infarction.","[{'text': 'isoproterenol', 'type': 'Chemical', 'start': 39, 'end': 52, 'mesh': 'D007545'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 61, 'end': 82, 'mesh': 'D009203'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 126, 'end': 139, 'mesh': 'D007545'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 148, 'end': 169, 'mesh': 'D009203'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 268, 'end': 281, 'mesh': 'D007545'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 418, 'end': 431, 'mesh': 'D007545'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 704, 'end': 717, 'mesh': 'D007545'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 850, 'end': 863, 'mesh': 'D007545'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1040, 'end': 1053, 'mesh': 'D007545'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1136, 'end': 1149, 'mesh': 'D007545'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1372, 'end': 1385, 'mesh': 'D007545'}, {'text': 'infarction', 'type': 'Disease', 'start': 1424, 'end': 1434, 'mesh': 'D007238'}]"
+1136,931801,Effect of D-Glucarates on basic antibiotic-induced renal damage in rats.,"Dehydrated rats regularly develop acute renal failure following single injection of aminoglycoside antibiotics combined with dextran or of antibiotics only. Oral administration of 2,5-di-O-acetyl-D-glucaro-1,4-6,3-dilactone protected rats against renal failure induced by kanamycin-dextran. The protective effect was prevalent among D-glucarates, and also to other saccharic acid, hexauronic acids and hexaaldonic acids, although to a lesser degree, but not to a hexaaldose, sugar alcohols, substances inthe TCA cycle and other acidic compounds. D-Glucarates were effective against renal damage induced by peptide antibiotics as well as various aminoglycoside antibitocis. Dose-responses were observed in the protective effect of D-Glucarates. With a D-glucarate of a fixed size of dose, approximately the same degree of protection was obtained against renal damages induced by different basic antibiotics despite large disparities in administration doses of different antibiotics. D-Glucarates had the ability to prevent renal damage but not to cure it. Rats excreted acidic urine when they were spared from renal lesions by monosaccharides. The reduction effect of D-glucarates against nephrotoxicity of basic antibiotics was discussed.","[{'text': 'D-Glucarates', 'type': 'Chemical', 'start': 10, 'end': 22, 'mesh': 'D005937'}, {'text': 'renal damage', 'type': 'Disease', 'start': 51, 'end': 63, 'mesh': 'D007674'}, {'text': 'Dehydrated', 'type': 'Disease', 'start': 73, 'end': 83, 'mesh': 'D003681'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 107, 'end': 126, 'mesh': 'D058186'}, {'text': 'aminoglycoside', 'type': 'Chemical', 'start': 157, 'end': 171, 'mesh': 'D000617'}, {'text': '2,5-di-O-acetyl-D-glucaro-1,4-6,3-dilactone', 'type': 'Chemical', 'start': 253, 'end': 296, 'mesh': 'C038936'}, {'text': 'renal failure', 'type': 'Disease', 'start': 320, 'end': 333, 'mesh': 'D051437'}, {'text': 'kanamycin', 'type': 'Chemical', 'start': 345, 'end': 354, 'mesh': 'D007612'}, {'text': 'D-glucarates', 'type': 'Chemical', 'start': 406, 'end': 418, 'mesh': 'D005937'}, {'text': 'saccharic acid', 'type': 'Chemical', 'start': 438, 'end': 452, 'mesh': 'D005937'}, {'text': 'hexauronic acids', 'type': 'Chemical', 'start': 454, 'end': 470, 'mesh': 'D006603'}, {'text': 'hexaaldonic acids', 'type': 'Chemical', 'start': 475, 'end': 492, 'mesh': '-1'}, {'text': 'sugar alcohols', 'type': 'Chemical', 'start': 548, 'end': 562, 'mesh': 'D013402'}, {'text': 'TCA', 'type': 'Chemical', 'start': 581, 'end': 584, 'mesh': 'D002952'}, {'text': 'D-Glucarates', 'type': 'Chemical', 'start': 619, 'end': 631, 'mesh': 'D005937'}, {'text': 'renal damage', 'type': 'Disease', 'start': 655, 'end': 667, 'mesh': 'D007674'}, {'text': 'aminoglycoside', 'type': 'Chemical', 'start': 718, 'end': 732, 'mesh': 'D000617'}, {'text': 'D-Glucarates', 'type': 'Chemical', 'start': 803, 'end': 815, 'mesh': 'D005937'}, {'text': 'D-glucarate', 'type': 'Chemical', 'start': 824, 'end': 835, 'mesh': 'D005937'}, {'text': 'renal damages', 'type': 'Disease', 'start': 926, 'end': 939, 'mesh': 'D007674'}, {'text': 'D-Glucarates', 'type': 'Chemical', 'start': 1055, 'end': 1067, 'mesh': 'D005937'}, {'text': 'renal damage', 'type': 'Disease', 'start': 1095, 'end': 1107, 'mesh': 'D007674'}, {'text': 'renal lesions', 'type': 'Disease', 'start': 1182, 'end': 1195, 'mesh': 'D007674'}, {'text': 'monosaccharides', 'type': 'Chemical', 'start': 1199, 'end': 1214, 'mesh': 'D009005'}, {'text': 'D-glucarates', 'type': 'Chemical', 'start': 1240, 'end': 1252, 'mesh': 'D005937'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1261, 'end': 1275, 'mesh': 'D007674'}]"
+1137,946593,Paraplegia following intrathecal methotrexate: report of a case and review of the literature.,"A patient who developed paraplegia following the intrathecal instillation of methotrexate is discribed. The ten previously reported cases of this unusual complication are reviewed. The following factors appear to predispose to the development of this complication: abnormal cerebrospinal dynamics related to the presence of central nervous system leukemia, and epidural cerebrospinal leakage; elevated cerebrospinal fluid methothexate concentration related to abnormal cerebrospinal fluid dynamics and to inappropriately high methotrexate doses based on body surface area calculations in older children and adults; the presence of neurotoxic preservatives in commercially available methotrexate preparations and diluents; and the use of methotrexate diluents of unphysiologic pH, ionic content and osmolarity. The role of methotrexate contaminants, local folate deficiency, and cranial irradiation in the pathogenesis of intrathecal methotrexate toxicity is unclear. The incidence of neurotoxicity may be reduced by employing lower doses of methotrexate in the presence of central nervous system leukemia, in older children and adults, and in the presence of epidural leakage. Only preservative-free methotrexate in Elliott's B Solution at a concentration of not more than 1 mg/ml should be used for intrathecal administration. Periodic monitoring of cerebruspinal fluid methotrexate levels may be predictive of the development of serious neurotoxicity.","[{'text': 'Paraplegia', 'type': 'Disease', 'start': 0, 'end': 10, 'mesh': 'D010264'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 33, 'end': 45, 'mesh': 'D008727'}, {'text': 'paraplegia', 'type': 'Disease', 'start': 118, 'end': 128, 'mesh': 'D010264'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 171, 'end': 183, 'mesh': 'D008727'}, {'text': 'central nervous system leukemia', 'type': 'Disease', 'start': 418, 'end': 449, 'mesh': 'D002493'}, {'text': 'methothexate', 'type': 'Chemical', 'start': 516, 'end': 528, 'mesh': 'D008727'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 620, 'end': 632, 'mesh': 'D008727'}, {'text': 'neurotoxic', 'type': 'Disease', 'start': 725, 'end': 735, 'mesh': 'D020258'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 776, 'end': 788, 'mesh': 'D008727'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 831, 'end': 843, 'mesh': 'D008727'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 916, 'end': 928, 'mesh': 'D008727'}, {'text': 'folate deficiency', 'type': 'Disease', 'start': 949, 'end': 966, 'mesh': 'C536409'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 1027, 'end': 1039, 'mesh': 'D008727'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1040, 'end': 1048, 'mesh': 'D064420'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 1078, 'end': 1091, 'mesh': 'D020258'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 1135, 'end': 1147, 'mesh': 'D008727'}, {'text': 'central nervous system leukemia', 'type': 'Disease', 'start': 1167, 'end': 1198, 'mesh': 'D002493'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 1294, 'end': 1306, 'mesh': 'D008727'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 1465, 'end': 1477, 'mesh': 'D008727'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 1533, 'end': 1546, 'mesh': 'D020258'}]"
+1138,978847,Centrally mediated cardiovascular effects of intracisternal application of carbachol in anesthetized rats.,"The pressor response to the intracisternal (i.c.) injection of carbachol (1 mug) in anesthetized rats was analyzed. This response was significantly reduced by the intravenous (i.v.) injection of guanethidine (5 mg), hexamethonium (10 mg) or phentolamine (5 mg), and conversely, potentiated by i.v. desmethylimipramine (0.3 mg), while propranolol (0.5 mg) i.v. selectively inhibited the enlargement of pulse pressure and the tachycardia following i.c. carbachol (1 mug). On the other hand, the pressor response to i.c. carbachol (1 mug) was almost completely blocked by i.c. atropine (3 mug) or hexamethonium (500 mug), and significantly reduced by i.c. chlorpromazine (50 mug) but significantly potentiated by i.c. desmethylimipramine (30 mug). The pressor response to i.c. carbachol (1 mug) remained unchanged after sectioning of the bilateral cervical vagal nerves but disappeared after sectioning of the spinal cord (C7-C8). From the above result it is suggested that the pressor response to i.c. carbachol ortral and peripheral adrenergic mechanisms, and that the sympathetic trunk is the main pathway.","[{'text': 'carbachol', 'type': 'Chemical', 'start': 75, 'end': 84, 'mesh': 'D002217'}, {'text': 'carbachol', 'type': 'Chemical', 'start': 170, 'end': 179, 'mesh': 'D002217'}, {'text': 'guanethidine', 'type': 'Chemical', 'start': 302, 'end': 314, 'mesh': 'D006145'}, {'text': 'hexamethonium', 'type': 'Chemical', 'start': 323, 'end': 336, 'mesh': 'D018738'}, {'text': 'phentolamine', 'type': 'Chemical', 'start': 348, 'end': 360, 'mesh': 'D010646'}, {'text': 'desmethylimipramine', 'type': 'Chemical', 'start': 405, 'end': 424, 'mesh': 'D003891'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 441, 'end': 452, 'mesh': 'D011433'}, {'text': 'enlargement of pulse pressure', 'type': 'Disease', 'start': 493, 'end': 522, 'mesh': 'D006973'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 531, 'end': 542, 'mesh': 'D013610'}, {'text': 'carbachol', 'type': 'Chemical', 'start': 558, 'end': 567, 'mesh': 'D002217'}, {'text': 'carbachol', 'type': 'Chemical', 'start': 625, 'end': 634, 'mesh': 'D002217'}, {'text': 'atropine', 'type': 'Chemical', 'start': 681, 'end': 689, 'mesh': 'D001285'}, {'text': 'hexamethonium', 'type': 'Chemical', 'start': 701, 'end': 714, 'mesh': 'D018738'}, {'text': 'chlorpromazine', 'type': 'Chemical', 'start': 760, 'end': 774, 'mesh': 'D002746'}, {'text': 'desmethylimipramine', 'type': 'Chemical', 'start': 822, 'end': 841, 'mesh': 'D003891'}, {'text': 'carbachol', 'type': 'Chemical', 'start': 881, 'end': 890, 'mesh': 'D002217'}, {'text': 'carbachol', 'type': 'Chemical', 'start': 1107, 'end': 1116, 'mesh': 'D002217'}]"
+1139,1117341,Hyperglycemic effect of amino compounds structurally related to caproate in rats.,"The chronic feeding of small amounts (0.3-3% of diet weight) of certain amino derivatives of caproate resulted in hyperglycemia, an elevated glucose tolerance curve and, occasionally, glucosuria. Effective compounds included norleucine, norvaline, glutamate, epsilon-aminocaproate, methionine, and leucine.","[{'text': 'Hyperglycemic', 'type': 'Disease', 'start': 0, 'end': 13, 'mesh': 'D006943'}, {'text': 'amino', 'type': 'Chemical', 'start': 24, 'end': 29, 'mesh': 'D015119'}, {'text': 'caproate', 'type': 'Chemical', 'start': 64, 'end': 72, 'mesh': 'C037652'}, {'text': 'amino', 'type': 'Chemical', 'start': 154, 'end': 159, 'mesh': 'D015119'}, {'text': 'caproate', 'type': 'Chemical', 'start': 175, 'end': 183, 'mesh': 'C037652'}, {'text': 'hyperglycemia', 'type': 'Disease', 'start': 196, 'end': 209, 'mesh': 'D006943'}, {'text': 'glucose', 'type': 'Chemical', 'start': 223, 'end': 230, 'mesh': 'D005947'}, {'text': 'glucosuria', 'type': 'Disease', 'start': 266, 'end': 276, 'mesh': 'D006030'}, {'text': 'norleucine', 'type': 'Chemical', 'start': 307, 'end': 317, 'mesh': '-1'}, {'text': 'norvaline', 'type': 'Chemical', 'start': 319, 'end': 328, 'mesh': '-1'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 330, 'end': 339, 'mesh': 'D018698'}, {'text': 'epsilon-aminocaproate', 'type': 'Chemical', 'start': 341, 'end': 362, 'mesh': '-1'}, {'text': 'methionine', 'type': 'Chemical', 'start': 364, 'end': 374, 'mesh': 'D008715'}, {'text': 'leucine', 'type': 'Chemical', 'start': 380, 'end': 387, 'mesh': '-1'}]"
+1140,1158089,Fatty liver induced by tetracycline in the rat. Dose-response relationships and effect of sex.,"Dose-response relationships, biochemical mechanisms, and sex differences in the experimental fatty liver induced by tetracycline were studied in the intact rat and with the isolated perfused rat liver in vitro. In the intact male and female rat, no direct relationship was observed between dose of tetracycline and hepatic accumulation of triglyceride. With provision of adequate oleic acid as a substrate for the isolated perfused liver, a direct relationship was observed between dose of tetracycline and both accumulation of triglyceride in the liver and depression of output of triglyceride by livers from male and female rats. Marked differences were observed between female and male rats with regard to base line (control) hepatic concentration of triglyceride and output of triglyceride. Accumulation of hepatic triglyceride, as a per cent of control values, in response to graded doses of tetracycline, did not differ significantly between male, female and pregnant rat livers. However, livers from female, and especially pregnant female rats, were strikingly resistant to the effects of tetracycline on depression of output of triglyceride under these experimental conditions. These differences between the sexes could not be related to altered disposition of tetracycline or altered uptake of oleic acid. Depressed hepatic secretion of triglyceride accounted only for 30 to 50% of accumulated hepatic triglyceride, indicating that additional mechanisms must be involved in the production of the triglyceride-rich fatty liver in response to tetracycline.","[{'text': 'Fatty liver', 'type': 'Disease', 'start': 0, 'end': 11, 'mesh': 'D005234'}, {'text': 'tetracycline', 'type': 'Chemical', 'start': 23, 'end': 35, 'mesh': 'D013752'}, {'text': 'fatty liver', 'type': 'Disease', 'start': 188, 'end': 199, 'mesh': 'D005234'}, {'text': 'tetracycline', 'type': 'Chemical', 'start': 211, 'end': 223, 'mesh': 'D013752'}, {'text': 'tetracycline', 'type': 'Chemical', 'start': 393, 'end': 405, 'mesh': 'D013752'}, {'text': 'triglyceride', 'type': 'Chemical', 'start': 434, 'end': 446, 'mesh': 'D014280'}, {'text': 'oleic acid', 'type': 'Chemical', 'start': 475, 'end': 485, 'mesh': 'D019301'}, {'text': 'tetracycline', 'type': 'Chemical', 'start': 585, 'end': 597, 'mesh': 'D013752'}, {'text': 'triglyceride', 'type': 'Chemical', 'start': 623, 'end': 635, 'mesh': 'D014280'}, {'text': 'depression', 'type': 'Disease', 'start': 653, 'end': 663, 'mesh': 'D003866'}, {'text': 'triglyceride', 'type': 'Chemical', 'start': 677, 'end': 689, 'mesh': 'D014280'}, {'text': 'triglyceride', 'type': 'Chemical', 'start': 849, 'end': 861, 'mesh': 'D014280'}, {'text': 'triglyceride', 'type': 'Chemical', 'start': 876, 'end': 888, 'mesh': 'D014280'}, {'text': 'triglyceride', 'type': 'Chemical', 'start': 914, 'end': 926, 'mesh': 'D014280'}, {'text': 'tetracycline', 'type': 'Chemical', 'start': 992, 'end': 1004, 'mesh': 'D013752'}, {'text': 'tetracycline', 'type': 'Chemical', 'start': 1191, 'end': 1203, 'mesh': 'D013752'}, {'text': 'depression', 'type': 'Disease', 'start': 1207, 'end': 1217, 'mesh': 'D003866'}, {'text': 'triglyceride', 'type': 'Chemical', 'start': 1231, 'end': 1243, 'mesh': 'D014280'}, {'text': 'tetracycline', 'type': 'Chemical', 'start': 1364, 'end': 1376, 'mesh': 'D013752'}, {'text': 'oleic acid', 'type': 'Chemical', 'start': 1398, 'end': 1408, 'mesh': 'D019301'}, {'text': 'triglyceride', 'type': 'Chemical', 'start': 1441, 'end': 1453, 'mesh': 'D014280'}, {'text': 'triglyceride', 'type': 'Chemical', 'start': 1506, 'end': 1518, 'mesh': 'D014280'}, {'text': 'triglyceride', 'type': 'Chemical', 'start': 1600, 'end': 1612, 'mesh': 'D014280'}, {'text': 'fatty liver', 'type': 'Disease', 'start': 1618, 'end': 1629, 'mesh': 'D005234'}, {'text': 'tetracycline', 'type': 'Chemical', 'start': 1645, 'end': 1657, 'mesh': 'D013752'}]"
+1141,1280054,Fatal myeloencephalopathy due to intrathecal vincristine administration.,"Vincristine was accidentally given intrathecally to a child with leukaemia, producing sensory and motor dysfunction followed by encephalopathy and death. Separate times for administering vincristine and intrathecal therapy is recommended.","[{'text': 'myeloencephalopathy', 'type': 'Disease', 'start': 6, 'end': 25, 'mesh': 'D001927'}, {'text': 'vincristine', 'type': 'Chemical', 'start': 45, 'end': 56, 'mesh': 'D014750'}, {'text': 'Vincristine', 'type': 'Chemical', 'start': 73, 'end': 84, 'mesh': 'D014750'}, {'text': 'leukaemia', 'type': 'Disease', 'start': 138, 'end': 147, 'mesh': 'D007938'}, {'text': 'sensory and motor dysfunction', 'type': 'Disease', 'start': 159, 'end': 188, 'mesh': 'D007049'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 201, 'end': 215, 'mesh': 'D001927'}, {'text': 'vincristine', 'type': 'Chemical', 'start': 260, 'end': 271, 'mesh': 'D014750'}]"
+1142,1280707,Progesterone potentiation of bupivacaine arrhythmogenicity in pentobarbital-anesthetized rats and beating rat heart cell cultures.,"The effects of progesterone treatment on bupivacaine arrhythmogenicity in beating rat heart myocyte cultures and on anesthetized rats were determined. After determining the bupivacaine AD50 (the concentration of bupivacaine that caused 50% of all beating rat heart myocyte cultures to become arrhythmic), we determined the effect of 1-hour progesterone HCl exposure on myocyte contractile rhythm. Each concentration of progesterone (6.25, 12.5, 25, and 50 micrograms/ml) caused a significant and concentration-dependent reduction in the AD50 for bupivacaine. Estradiol treatment also increased the arrhythmogenicity of bupivacaine in myocyte cultures, but was only one fourth as potent as progesterone. Neither progesterone nor estradiol effects on bupivacaine arrhythmogenicity were potentiated by epinephrine. Chronic progesterone pretreatment (5 mg/kg/day for 21 days) caused a significant increase in bupivacaine arrhythmogenicity in intact pentobarbital-anesthetized rats. There was a significant decrease in the time to onset of arrhythmia as compared with control nonprogesterone-treated rats (6.2 +/- 1.3 vs. 30.8 +/- 2.5 min, mean +/- SE). The results of this study indicate that progesterone can potentiate bupivacaine arrhythmogenicity both in vivo and in vitro. Potentiation of bupivacaine arrhythmia in myocyte cultures suggests that this effect is at least partly mediated at the myocyte level.","[{'text': 'Progesterone', 'type': 'Chemical', 'start': 0, 'end': 12, 'mesh': 'D011374'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 29, 'end': 40, 'mesh': 'D002045'}, {'text': 'pentobarbital', 'type': 'Chemical', 'start': 62, 'end': 75, 'mesh': 'D010424'}, {'text': 'progesterone', 'type': 'Chemical', 'start': 146, 'end': 158, 'mesh': 'D011374'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 172, 'end': 183, 'mesh': 'D002045'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 304, 'end': 315, 'mesh': 'D002045'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 343, 'end': 354, 'mesh': 'D002045'}, {'text': 'arrhythmic', 'type': 'Disease', 'start': 423, 'end': 433, 'mesh': 'D001145'}, {'text': 'progesterone', 'type': 'Chemical', 'start': 471, 'end': 483, 'mesh': 'D011374'}, {'text': 'HCl', 'type': 'Chemical', 'start': 484, 'end': 487, 'mesh': 'D006851'}, {'text': 'progesterone', 'type': 'Chemical', 'start': 550, 'end': 562, 'mesh': 'D011374'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 677, 'end': 688, 'mesh': 'D002045'}, {'text': 'Estradiol', 'type': 'Chemical', 'start': 690, 'end': 699, 'mesh': 'D004958'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 750, 'end': 761, 'mesh': 'D002045'}, {'text': 'progesterone', 'type': 'Chemical', 'start': 820, 'end': 832, 'mesh': 'D011374'}, {'text': 'progesterone', 'type': 'Chemical', 'start': 842, 'end': 854, 'mesh': 'D011374'}, {'text': 'estradiol', 'type': 'Chemical', 'start': 859, 'end': 868, 'mesh': 'D004958'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 880, 'end': 891, 'mesh': 'D002045'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 930, 'end': 941, 'mesh': 'D004837'}, {'text': 'progesterone', 'type': 'Chemical', 'start': 951, 'end': 963, 'mesh': 'D011374'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 1036, 'end': 1047, 'mesh': 'D002045'}, {'text': 'pentobarbital', 'type': 'Chemical', 'start': 1076, 'end': 1089, 'mesh': 'D010424'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 1166, 'end': 1176, 'mesh': 'D001145'}, {'text': 'progesterone', 'type': 'Chemical', 'start': 1320, 'end': 1332, 'mesh': 'D011374'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 1348, 'end': 1359, 'mesh': 'D002045'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 1421, 'end': 1432, 'mesh': 'D002045'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 1433, 'end': 1443, 'mesh': 'D001145'}]"
+1143,1289188,Acute renal failure occurring during intravenous desferrioxamine therapy: recovery after haemodialysis.,"A patient with transfusion-dependent thalassemia was undergoing home intravenous desferrioxamine (DFX) treatment by means of a totally implanted system because of his poor compliance with the nightly subcutaneous therapy. Due to an accidental malfunctioning of the infusion pump, the patient was inadvertently administered a toxic dosage of the drug which caused renal insufficiency. Given the progressive deterioration of the symptoms and of the laboratory values, despite adequate medical treatment, a decision was made to introduce haemodialytical therapy in order to remove the drug and therapy reduce the nephrotoxicity. From the results obtained, haemodialysis can therefore be suggested as a useful therapy in rare cases of progressive acute renal failure caused by desferrioxamine.","[{'text': 'Acute renal failure', 'type': 'Disease', 'start': 0, 'end': 19, 'mesh': 'D058186'}, {'text': 'desferrioxamine', 'type': 'Chemical', 'start': 49, 'end': 64, 'mesh': 'D003676'}, {'text': 'thalassemia', 'type': 'Disease', 'start': 141, 'end': 152, 'mesh': 'D013789'}, {'text': 'desferrioxamine', 'type': 'Chemical', 'start': 185, 'end': 200, 'mesh': 'D003676'}, {'text': 'DFX', 'type': 'Chemical', 'start': 202, 'end': 205, 'mesh': 'D003676'}, {'text': 'renal insufficiency', 'type': 'Disease', 'start': 467, 'end': 486, 'mesh': 'D051437'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 714, 'end': 728, 'mesh': 'D007674'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 847, 'end': 866, 'mesh': 'D058186'}, {'text': 'desferrioxamine', 'type': 'Chemical', 'start': 877, 'end': 892, 'mesh': 'D003676'}]"
+1144,1359137,Neuroleptic-associated hyperprolactinemia. Can it be treated with bromocriptine?,"Six stable psychiatric outpatients with hyperprolactinemia and amenorrhea/oligomenorrhea associated with their neuroleptic medications were treated with bromocriptine. Daily dosages of 5-10 mg corrected the hyperprolactinemia and restored menstruation in four of the six patients. One woman, however, developed worsened psychiatric symptoms while taking bromocriptine, and it was discontinued. Thus, three of six patients had their menstrual irregularity successfully corrected with bromocriptine. This suggests that bromocriptine should be further evaluated as potential therapy for neuroleptic-associated hyperprolactinemia and amenorrhea/galactorrhea.","[{'text': 'Neuroleptic', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D014150'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 23, 'end': 41, 'mesh': 'D006966'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 66, 'end': 79, 'mesh': 'D001971'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 121, 'end': 139, 'mesh': 'D006966'}, {'text': 'amenorrhea', 'type': 'Disease', 'start': 144, 'end': 154, 'mesh': 'D000568'}, {'text': 'oligomenorrhea', 'type': 'Disease', 'start': 155, 'end': 169, 'mesh': 'D009839'}, {'text': 'neuroleptic medications', 'type': 'Chemical', 'start': 192, 'end': 215, 'mesh': 'D014150'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 234, 'end': 247, 'mesh': 'D001971'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 288, 'end': 306, 'mesh': 'D006966'}, {'text': 'psychiatric symptoms', 'type': 'Disease', 'start': 401, 'end': 421, 'mesh': 'D011618'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 435, 'end': 448, 'mesh': 'D001971'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 564, 'end': 577, 'mesh': 'D001971'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 598, 'end': 611, 'mesh': 'D001971'}, {'text': 'neuroleptic', 'type': 'Chemical', 'start': 665, 'end': 676, 'mesh': 'D014150'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 688, 'end': 706, 'mesh': 'D006966'}, {'text': 'amenorrhea', 'type': 'Disease', 'start': 711, 'end': 721, 'mesh': 'D000568'}, {'text': 'galactorrhea', 'type': 'Disease', 'start': 722, 'end': 734, 'mesh': 'D005687'}]"
+1145,1360900,Ethacrynic acid-induced convulsions and brain neurotransmitters in mice.,"Intracerebroventricular injection of ethacrynic acid (50% convulsive dose; 50 micrograms/mouse) accelerated the synthesis/turnover of 5-hydroxytryptamine (5-HT) but suppressed the synthesis of gamma-aminobutyric acid and acetylcholine in mouse brain. These effects were completely antagonized by pretreatment with a glutamate/N-methyl-D-aspartate antagonist, aminophosphonovaleric acid. In ethacrynic acid-induced convulsions, these neurotransmitter systems may be differentially modulated, probably through activation of glutaminergic neurons in the brain.","[{'text': 'Ethacrynic acid', 'type': 'Chemical', 'start': 0, 'end': 15, 'mesh': 'D004976'}, {'text': 'convulsions', 'type': 'Disease', 'start': 24, 'end': 35, 'mesh': 'D012640'}, {'text': 'ethacrynic acid', 'type': 'Chemical', 'start': 110, 'end': 125, 'mesh': 'D004976'}, {'text': 'convulsive', 'type': 'Disease', 'start': 131, 'end': 141, 'mesh': 'D012640'}, {'text': '5-hydroxytryptamine', 'type': 'Chemical', 'start': 207, 'end': 226, 'mesh': 'D012701'}, {'text': '5-HT', 'type': 'Chemical', 'start': 228, 'end': 232, 'mesh': 'D012701'}, {'text': 'gamma-aminobutyric acid', 'type': 'Chemical', 'start': 266, 'end': 289, 'mesh': 'D005680'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 294, 'end': 307, 'mesh': 'D000109'}, {'text': 'glutamate', 'type': 'Chemical', 'start': 389, 'end': 398, 'mesh': 'D018698'}, {'text': 'N-methyl-D-aspartate', 'type': 'Chemical', 'start': 399, 'end': 419, 'mesh': 'D016202'}, {'text': 'aminophosphonovaleric acid', 'type': 'Chemical', 'start': 432, 'end': 458, 'mesh': '-1'}, {'text': 'ethacrynic acid', 'type': 'Chemical', 'start': 463, 'end': 478, 'mesh': 'D004976'}, {'text': 'convulsions', 'type': 'Disease', 'start': 487, 'end': 498, 'mesh': 'D012640'}]"
+1146,1361574,Pharmacology of gamma-aminobutyric acidA receptor complex after the in vivo administration of the anxioselective and anticonvulsant beta-carboline derivative abecarnil.,"In rodents, the effect of the beta-carboline derivative isopropyl-6- benzyloxy-4-methoxymethyl-beta-carboline-3-carboxylate (abecarrnil), a new ligand for benzodiazepine receptors possessing anxiolytic and anticonvulsant properties, was evaluated on the function of central gamma-aminobutyric acid (GABA)A receptor complex, both in vitro and in vivo. Added in vitro to rat cortical membrane preparation, abecarnil increased [3H]GABA binding, enhanced muscimol-stimulated 36Cl- uptake and reduced the binding of t-[35S]butylbicyclophosphorothionate ([35S]TBPS). These effects were similar to those induced by diazepam, whereas the partial agonist Ro 16-6028 (tert-butyl-(S)-8-bromo-11,12,13,13a-tetrahydro-9-oxo-9H- imidazo[1,5-a]-pyrrolo-[2,1-c][1,4]benzodiazepine-1-carboxylate) showed very weak efficacy in these biochemical tests. After i.p. injection to rats, abecarnil and diazepam decreased in a time-dependent and dose-related (0.25-20 mg/kg i.p.) manner [35S]TBPS binding measured ex vivo in the cerebral cortex. Moreover, both drugs at the dose of 0.5 mg/kg antagonized completely the convulsant activity and the increase of [35S]TBPS binding induced by isoniazide (350 mg/kg s.c.) as well as the increase of [35S]TBPS binding induced by foot-shock stress. To better correlate the biochemical and the pharmacological effects, we studied the action of abecarnil on [35S]TBPS binding, exploratory motility and on isoniazid-induced biochemical and pharmacological effects in mice. In these animals, abecarnil produced a paralleled dose-dependent (0.05-1 mg/kg i.p.) reduction of both motor behavior and cortical [35S]TBPS binding. Moreover, 0.05 mg/kg of this beta-carboline reduced markedly the increase of [35S]TBPS binding and the convulsions induced by isoniazid (200 mg/kg s.c.).(ABSTRACT TRUNCATED AT 250 WORDS)","[{'text': 'gamma-aminobutyric acid', 'type': 'Chemical', 'start': 16, 'end': 39, 'mesh': 'D005680'}, {'text': 'beta-carboline', 'type': 'Chemical', 'start': 132, 'end': 146, 'mesh': 'D002243'}, {'text': 'abecarnil', 'type': 'Chemical', 'start': 158, 'end': 167, 'mesh': 'C062769'}, {'text': 'beta-carboline', 'type': 'Chemical', 'start': 199, 'end': 213, 'mesh': 'D002243'}, {'text': 'isopropyl-6- benzyloxy-4-methoxymethyl-beta-carboline-3-carboxylate', 'type': 'Chemical', 'start': 225, 'end': 292, 'mesh': 'C062769'}, {'text': 'abecarrnil', 'type': 'Chemical', 'start': 294, 'end': 304, 'mesh': 'C062769'}, {'text': 'benzodiazepine', 'type': 'Chemical', 'start': 324, 'end': 338, 'mesh': 'D001569'}, {'text': 'gamma-aminobutyric acid', 'type': 'Chemical', 'start': 443, 'end': 466, 'mesh': 'D005680'}, {'text': 'GABA', 'type': 'Chemical', 'start': 468, 'end': 472, 'mesh': 'D005680'}, {'text': 'abecarnil', 'type': 'Chemical', 'start': 573, 'end': 582, 'mesh': 'C062769'}, {'text': 'GABA', 'type': 'Chemical', 'start': 597, 'end': 601, 'mesh': 'D005680'}, {'text': 'muscimol', 'type': 'Chemical', 'start': 620, 'end': 628, 'mesh': 'D009118'}, {'text': 't-[35S]butylbicyclophosphorothionate', 'type': 'Chemical', 'start': 680, 'end': 716, 'mesh': 'C037476'}, {'text': '[35S]TBPS', 'type': 'Chemical', 'start': 718, 'end': 727, 'mesh': 'C037476'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 777, 'end': 785, 'mesh': 'D003975'}, {'text': 'Ro 16-6028', 'type': 'Chemical', 'start': 815, 'end': 825, 'mesh': 'C054626'}, {'text': 'tert-butyl-(S)-8-bromo-11,12,13,13a-tetrahydro-9-oxo-9H- imidazo[1,5-a]-pyrrolo-[2,1-c][1,4]benzodiazepine-1-carboxylate', 'type': 'Chemical', 'start': 827, 'end': 947, 'mesh': 'C054626'}, {'text': 'abecarnil', 'type': 'Chemical', 'start': 1033, 'end': 1042, 'mesh': 'C062769'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 1047, 'end': 1055, 'mesh': 'D003975'}, {'text': '[35S]TBPS', 'type': 'Chemical', 'start': 1131, 'end': 1140, 'mesh': 'C037476'}, {'text': '[35S]TBPS', 'type': 'Chemical', 'start': 1303, 'end': 1312, 'mesh': 'C037476'}, {'text': 'isoniazide', 'type': 'Chemical', 'start': 1332, 'end': 1342, 'mesh': 'D007538'}, {'text': '[35S]TBPS', 'type': 'Chemical', 'start': 1387, 'end': 1396, 'mesh': 'C037476'}, {'text': 'abecarnil', 'type': 'Chemical', 'start': 1529, 'end': 1538, 'mesh': 'C062769'}, {'text': '[35S]TBPS', 'type': 'Chemical', 'start': 1542, 'end': 1551, 'mesh': 'C037476'}, {'text': 'isoniazid', 'type': 'Chemical', 'start': 1589, 'end': 1598, 'mesh': 'D007538'}, {'text': 'abecarnil', 'type': 'Chemical', 'start': 1674, 'end': 1683, 'mesh': 'C062769'}, {'text': 'beta-carboline', 'type': 'Chemical', 'start': 1835, 'end': 1849, 'mesh': 'D002243'}, {'text': '[35S]TBPS', 'type': 'Chemical', 'start': 1883, 'end': 1892, 'mesh': 'C037476'}, {'text': 'convulsions', 'type': 'Disease', 'start': 1909, 'end': 1920, 'mesh': 'D012640'}, {'text': 'isoniazid', 'type': 'Chemical', 'start': 1932, 'end': 1941, 'mesh': 'D007538'}]"
+1147,1395192,Recurrent myocardial infarction in a postpartum patient receiving bromocriptine.,"Myocardial infarction in puerperium is infrequently reported. Spasm, coronary dissection, or atheromatous etiology has been described. Bromocriptine has been implicated in several previous case reports of myocardial infarction in the puerperium. Our case (including an inadvertent rechallenge) suggests such a relationship. Although generally regarded as ""safe,"" possible serious cardiac effects of bromocriptine should be acknowledged.","[{'text': 'myocardial infarction', 'type': 'Disease', 'start': 10, 'end': 31, 'mesh': 'D009203'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 66, 'end': 79, 'mesh': 'D001971'}, {'text': 'Myocardial infarction', 'type': 'Disease', 'start': 81, 'end': 102, 'mesh': 'D009203'}, {'text': 'Spasm', 'type': 'Disease', 'start': 143, 'end': 148, 'mesh': 'D013035'}, {'text': 'Bromocriptine', 'type': 'Chemical', 'start': 216, 'end': 229, 'mesh': 'D001971'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 286, 'end': 307, 'mesh': 'D009203'}, {'text': 'bromocriptine', 'type': 'Chemical', 'start': 480, 'end': 493, 'mesh': 'D001971'}]"
+1148,1420650,Asterixis induced by carbamazepine therapy.,"There are very few reports about asterixis as a side effect of treatment with psychopharmacologic agents. In this report we present four patients treated with a combination of different psychotropic drugs, in whom asterixis was triggered either by adding carbamazepine (CBZ) to a treatment regimen, or by increasing its dosage. Neither dosage nor serum levels of CBZ were in a higher range. We consider asterixis to be an easily overlooked sign of neurotoxicity, which may occur even at low or moderate dosage levels, if certain drugs as lithium or clozapine are used in combination with CBZ.","[{'text': 'Asterixis', 'type': 'Disease', 'start': 0, 'end': 9, 'mesh': 'D020820'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 21, 'end': 34, 'mesh': 'D002220'}, {'text': 'asterixis', 'type': 'Disease', 'start': 77, 'end': 86, 'mesh': 'D020820'}, {'text': 'asterixis', 'type': 'Disease', 'start': 258, 'end': 267, 'mesh': 'D020820'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 299, 'end': 312, 'mesh': 'D002220'}, {'text': 'CBZ', 'type': 'Chemical', 'start': 314, 'end': 317, 'mesh': 'D002220'}, {'text': 'CBZ', 'type': 'Chemical', 'start': 407, 'end': 410, 'mesh': 'D002220'}, {'text': 'asterixis', 'type': 'Disease', 'start': 447, 'end': 456, 'mesh': 'D020820'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 492, 'end': 505, 'mesh': 'D020258'}, {'text': 'lithium', 'type': 'Chemical', 'start': 582, 'end': 589, 'mesh': 'D008094'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 593, 'end': 602, 'mesh': 'D003024'}, {'text': 'CBZ', 'type': 'Chemical', 'start': 632, 'end': 635, 'mesh': 'D002220'}]"
+1149,1423336,Pharmacodynamics of the hypotensive effect of levodopa in parkinsonian patients.,"Blood pressure effects of i.v. levodopa were examined in parkinsonian patients with stable and fluctuating responses to levodopa. The magnitude of the hypotensive effect of levodopa was concentration dependent and was fit to an Emax model in fluctuating responders. Stable responders demonstrated a small hypotensive response. Baseline blood pressures were higher in fluctuating patients; a higher baseline blood pressure correlated with greater hypotensive effects. Antiparkinsonian effects of levodopa temporally correlated with blood pressure changes. Phenylalanine, a large neutral amino acid (LNAA) competing with levodopa for transport across the blood-brain barrier, reduced the hypotensive and antiparkinsonian effects of levodopa. We conclude that levodopa has a central hypotensive action that parallels the motor effects in fluctuating patients. The hypotensive effect appears to be related to the higher baseline blood pressure we observed in fluctuating patients relative to stable patients.","[{'text': 'hypotensive', 'type': 'Disease', 'start': 24, 'end': 35, 'mesh': 'D007022'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 46, 'end': 54, 'mesh': 'D007980'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 58, 'end': 70, 'mesh': 'D010300'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 112, 'end': 120, 'mesh': 'D007980'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 138, 'end': 150, 'mesh': 'D010300'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 201, 'end': 209, 'mesh': 'D007980'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 232, 'end': 243, 'mesh': 'D007022'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 254, 'end': 262, 'mesh': 'D007980'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 386, 'end': 397, 'mesh': 'D007022'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 527, 'end': 538, 'mesh': 'D007022'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 576, 'end': 584, 'mesh': 'D007980'}, {'text': 'Phenylalanine', 'type': 'Chemical', 'start': 636, 'end': 649, 'mesh': 'D010649'}, {'text': 'amino acid', 'type': 'Chemical', 'start': 667, 'end': 677, 'mesh': 'D000596'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 700, 'end': 708, 'mesh': 'D007980'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 767, 'end': 778, 'mesh': 'D007022'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 811, 'end': 819, 'mesh': 'D007980'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 838, 'end': 846, 'mesh': 'D007980'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 861, 'end': 872, 'mesh': 'D007022'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 942, 'end': 953, 'mesh': 'D007022'}]"
+1150,1424076,Syndrome of inappropriate secretion of antidiuretic hormone after infusional vincristine.,"A 77-year-old woman with refractory multiple myeloma was treated with a 4-day continuous intravenous infusion of vincristine and doxorubicin and 4 days of oral dexamethasone. Nine days after her second cycle she presented with lethargy and weakness associated with hyponatremia. Evaluation revealed the syndrome of inappropriate secretion of antidiuretic hormone, which was attributed to the vincristine infusion. After normal serum sodium levels returned, further doxorubicin and dexamethasone chemotherapy without vincristine did not produce this complication.","[{'text': 'Syndrome of inappropriate secretion of antidiuretic hormone', 'type': 'Disease', 'start': 0, 'end': 59, 'mesh': 'D007177'}, {'text': 'vincristine', 'type': 'Chemical', 'start': 77, 'end': 88, 'mesh': 'D014750'}, {'text': 'multiple myeloma', 'type': 'Disease', 'start': 126, 'end': 142, 'mesh': 'D009101'}, {'text': 'vincristine', 'type': 'Chemical', 'start': 203, 'end': 214, 'mesh': 'D014750'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 219, 'end': 230, 'mesh': 'D004317'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 250, 'end': 263, 'mesh': 'D003907'}, {'text': 'lethargy', 'type': 'Disease', 'start': 317, 'end': 325, 'mesh': 'D053609'}, {'text': 'weakness', 'type': 'Disease', 'start': 330, 'end': 338, 'mesh': 'D018908'}, {'text': 'hyponatremia', 'type': 'Disease', 'start': 355, 'end': 367, 'mesh': 'D007010'}, {'text': 'syndrome of inappropriate secretion of antidiuretic hormone', 'type': 'Disease', 'start': 393, 'end': 452, 'mesh': 'D007177'}, {'text': 'vincristine', 'type': 'Chemical', 'start': 482, 'end': 493, 'mesh': 'D014750'}, {'text': 'sodium', 'type': 'Chemical', 'start': 523, 'end': 529, 'mesh': 'D012964'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 555, 'end': 566, 'mesh': 'D004317'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 571, 'end': 584, 'mesh': 'D003907'}, {'text': 'vincristine', 'type': 'Chemical', 'start': 606, 'end': 617, 'mesh': 'D014750'}]"
+1151,1449452,Heart failure: to digitalise or not? The view against.,"Despite extensive clinical experience the role of digoxin is still not well defined. In patients with atrial fibrillation digoxin is beneficial for ventricular rate control. For patients in sinus rhythm and heart failure the situation is less clear. Digoxin has a narrow therapeutic:toxic ratio and concentrations are affected by a number of drugs. Also, digoxin has undesirable effects such as increasing peripheral resistance and myocardial demands, and causing arrhythmias. There is a paucity of data from well-designed trials. The trials that are available are generally small with limitations in design and these show variation in patient benefit. More convincing evidence is required showing that digoxin improves symptoms or exercise capacity. Furthermore, no trial has had sufficient power to evaluate mortality. Pooled analysis of the effects of other inotropic drugs shows an excess mortality and there is a possibility that digoxin may increase mortality after myocardial infarction (MI). Angiotensin-converting enzyme (ACE) inhibitors should be used first as they are safer, do not require blood level monitoring, modify progression of disease, relieve symptoms, improve exercise tolerance and reduce mortality. Caution should be exercised in using digoxin until large mortality trials are completed showing either benefit or harm. Until then digoxin should be considered a third-line therapy.","[{'text': 'Heart failure', 'type': 'Disease', 'start': 0, 'end': 13, 'mesh': 'D006333'}, {'text': 'digoxin', 'type': 'Chemical', 'start': 105, 'end': 112, 'mesh': 'D004077'}, {'text': 'atrial fibrillation', 'type': 'Disease', 'start': 157, 'end': 176, 'mesh': 'D001281'}, {'text': 'digoxin', 'type': 'Chemical', 'start': 177, 'end': 184, 'mesh': 'D004077'}, {'text': 'heart failure', 'type': 'Disease', 'start': 262, 'end': 275, 'mesh': 'D006333'}, {'text': 'Digoxin', 'type': 'Chemical', 'start': 305, 'end': 312, 'mesh': 'D004077'}, {'text': 'digoxin', 'type': 'Chemical', 'start': 410, 'end': 417, 'mesh': 'D004077'}, {'text': 'arrhythmias', 'type': 'Disease', 'start': 519, 'end': 530, 'mesh': 'D001145'}, {'text': 'digoxin', 'type': 'Chemical', 'start': 758, 'end': 765, 'mesh': 'D004077'}, {'text': 'digoxin', 'type': 'Chemical', 'start': 990, 'end': 997, 'mesh': 'D004077'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 1027, 'end': 1048, 'mesh': 'D009203'}, {'text': 'MI', 'type': 'Disease', 'start': 1050, 'end': 1052, 'mesh': 'D009203'}, {'text': 'Angiotensin', 'type': 'Chemical', 'start': 1055, 'end': 1066, 'mesh': 'D000809'}, {'text': 'digoxin', 'type': 'Chemical', 'start': 1316, 'end': 1323, 'mesh': 'D004077'}, {'text': 'digoxin', 'type': 'Chemical', 'start': 1410, 'end': 1417, 'mesh': 'D004077'}]"
+1152,1522360,Intravascular hemolysis and acute renal failure following intermittent rifampin therapy.,Renal failure is a rare complication associated with the use of rifampin. Intravascular hemolysis leading to acute renal failure following rifampin therapy is extremely rare. Two patients with leprosy who developed hemolysis and acute renal failure following rifampin are reported.,"[{'text': 'hemolysis', 'type': 'Disease', 'start': 14, 'end': 23, 'mesh': 'D006461'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 28, 'end': 47, 'mesh': 'D058186'}, {'text': 'rifampin', 'type': 'Chemical', 'start': 71, 'end': 79, 'mesh': 'D012293'}, {'text': 'Renal failure', 'type': 'Disease', 'start': 89, 'end': 102, 'mesh': 'D051437'}, {'text': 'rifampin', 'type': 'Chemical', 'start': 153, 'end': 161, 'mesh': 'D012293'}, {'text': 'hemolysis', 'type': 'Disease', 'start': 177, 'end': 186, 'mesh': 'D006461'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 198, 'end': 217, 'mesh': 'D058186'}, {'text': 'rifampin', 'type': 'Chemical', 'start': 228, 'end': 236, 'mesh': 'D012293'}, {'text': 'leprosy', 'type': 'Disease', 'start': 282, 'end': 289, 'mesh': 'D007918'}, {'text': 'hemolysis', 'type': 'Disease', 'start': 304, 'end': 313, 'mesh': 'D006461'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 318, 'end': 337, 'mesh': 'D058186'}, {'text': 'rifampin', 'type': 'Chemical', 'start': 348, 'end': 356, 'mesh': 'D012293'}]"
+1153,1556529,Zidovudine-induced hepatitis.,"A case of acute hepatitis induced by zidovudine in a 38-year-old patient with AIDS is presented. The mechanism whereby the hepatitis was induced is not known. However, the patient tolerated well an alternative reverse transcriptase inhibitor, 2'3' dideoxyinosine. Physicians caring for patients with AIDS should be aware of this hitherto rarely reported complication.","[{'text': 'Zidovudine', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D015215'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 19, 'end': 28, 'mesh': 'D056486'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 46, 'end': 55, 'mesh': 'D056486'}, {'text': 'zidovudine', 'type': 'Chemical', 'start': 67, 'end': 77, 'mesh': 'D015215'}, {'text': 'AIDS', 'type': 'Disease', 'start': 108, 'end': 112, 'mesh': 'D000163'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 153, 'end': 162, 'mesh': 'D056486'}, {'text': ""2'3' dideoxyinosine"", 'type': 'Chemical', 'start': 273, 'end': 292, 'mesh': 'D016049'}, {'text': 'AIDS', 'type': 'Disease', 'start': 330, 'end': 334, 'mesh': 'D000163'}]"
+1154,1563460,Thoracic hematomyelia secondary to coumadin anticoagulant therapy: a case report.,"A case of thoracic hematomyelia secondary to anticoagulant therapy is presented. Clinical features, similar to 2 other previously reported cases, are discussed. A high index of suspicion may lead to a quick diagnostic procedure and successful decompressive surgery.","[{'text': 'Thoracic hematomyelia', 'type': 'Disease', 'start': 0, 'end': 21, 'mesh': 'D020758'}, {'text': 'coumadin', 'type': 'Chemical', 'start': 35, 'end': 43, 'mesh': 'D014859'}, {'text': 'thoracic hematomyelia', 'type': 'Disease', 'start': 92, 'end': 113, 'mesh': 'D020758'}]"
+1155,1564030,Mania associated with fluoxetine treatment in adolescents.,"Fluoxetine, a selective serotonin reuptake inhibitor, is gaining increased acceptance in the treatment of adolescent depression. Generally safe and well tolerated by adults, fluoxetine has been reported to induce mania. The cases of five depressed adolescents, 14-16 years of age, who developed mania during pharmacotherapy with fluoxetine, are reported here. Apparent risk factors for the development of mania or hypomania during fluoxetine pharmacotherapy in this population were the combination of attention-deficit hyperactivity disorder and affective instability; major depression with psychotic features; a family history of affective disorder, especially bipolar disorder; and a diagnosis of bipolar disorder. Further study is needed to determine the optimal dosage and to identify risk factors that increase individual vulnerability to fluoxetine induced mania in adolescents.","[{'text': 'Mania', 'type': 'Disease', 'start': 0, 'end': 5, 'mesh': 'D001714'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 22, 'end': 32, 'mesh': 'D005473'}, {'text': 'Fluoxetine', 'type': 'Chemical', 'start': 59, 'end': 69, 'mesh': 'D005473'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 83, 'end': 92, 'mesh': 'D012701'}, {'text': 'depression', 'type': 'Disease', 'start': 176, 'end': 186, 'mesh': 'D003866'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 233, 'end': 243, 'mesh': 'D005473'}, {'text': 'mania', 'type': 'Disease', 'start': 272, 'end': 277, 'mesh': 'D001714'}, {'text': 'depressed', 'type': 'Disease', 'start': 297, 'end': 306, 'mesh': 'D003866'}, {'text': 'mania', 'type': 'Disease', 'start': 354, 'end': 359, 'mesh': 'D001714'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 388, 'end': 398, 'mesh': 'D005473'}, {'text': 'mania', 'type': 'Disease', 'start': 464, 'end': 469, 'mesh': 'D001714'}, {'text': 'hypomania', 'type': 'Disease', 'start': 473, 'end': 482, 'mesh': 'D001714'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 490, 'end': 500, 'mesh': 'D005473'}, {'text': 'attention-deficit hyperactivity disorder', 'type': 'Disease', 'start': 560, 'end': 600, 'mesh': 'D001289'}, {'text': 'depression', 'type': 'Disease', 'start': 634, 'end': 644, 'mesh': 'D003866'}, {'text': 'psychotic', 'type': 'Disease', 'start': 650, 'end': 659, 'mesh': 'D011618'}, {'text': 'affective disorder', 'type': 'Disease', 'start': 690, 'end': 708, 'mesh': 'D019964'}, {'text': 'bipolar disorder', 'type': 'Disease', 'start': 721, 'end': 737, 'mesh': 'D001714'}, {'text': 'bipolar disorder', 'type': 'Disease', 'start': 758, 'end': 774, 'mesh': 'D001714'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 903, 'end': 913, 'mesh': 'D005473'}, {'text': 'mania', 'type': 'Disease', 'start': 922, 'end': 927, 'mesh': 'D001714'}]"
+1156,1615846,Gemfibrozil-lovastatin therapy for primary hyperlipoproteinemias.,"The specific aim of this retrospective, observational study was to assess safety and efficacy of long-term (21 months/patient), open-label, gemfibrozil-lovastatin treatment in 80 patients with primary mixed hyperlipidemia (68% of whom had atherosclerotic vascular disease). Because ideal lipid targets were not reached (low-density lipoprotein (LDL) cholesterol less than 130 mg/dl, high-density lipoprotein (HDL) cholesterol greater than 35 mg/dl, or total cholesterol/HDL cholesterol less than 4.5 mg/dl) with diet plus a single drug, gemfibrozil (1.2 g/day)-lovastatin (primarily 20 or 40 mg) treatment was given. Follow-up visits were scheduled with 2-drug therapy every 6 to 8 weeks, an average of 10.3 visits per patient, with 741 batteries of 6 liver function tests and 714 creatine phosphokinase levels measured. Only 1 of the 4,446 liver function tests (0.02%), a gamma glutamyl transferase, was greater than or equal to 3 times the upper normal limit. Of the 714 creatine phosphokinase levels, 9% were high; only 1 (0.1%) was greater than or equal to 3 times the upper normal limit. With 2-drug therapy, mean total cholesterol decreased 22% from 255 to 200 mg/dl, triglyceride levels decreased 35% from 236 to 154 mg/dl, LDL cholesterol decreased 26% from 176 to 131 mg/dl, and the total cholesterol/HDL cholesterol ratio decreased 24% from 7.1 to 5.4, all p less than or equal to 0.0001. Myositis, attributable to the drug combination and symptomatic enough to discontinue it, occurred in 3% of patients, and in 1% with concurrent high creatine phosphokinase (769 U/liter); no patients had rhabdomyolysis or myoglobinuria.(ABSTRACT TRUNCATED AT 250 WORDS)","[{'text': 'Gemfibrozil', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D015248'}, {'text': 'lovastatin', 'type': 'Chemical', 'start': 12, 'end': 22, 'mesh': 'D008148'}, {'text': 'hyperlipoproteinemias', 'type': 'Disease', 'start': 43, 'end': 64, 'mesh': 'D006951'}, {'text': 'gemfibrozil', 'type': 'Chemical', 'start': 206, 'end': 217, 'mesh': 'D015248'}, {'text': 'lovastatin', 'type': 'Chemical', 'start': 218, 'end': 228, 'mesh': 'D008148'}, {'text': 'hyperlipidemia', 'type': 'Disease', 'start': 273, 'end': 287, 'mesh': 'D006949'}, {'text': 'atherosclerotic vascular disease', 'type': 'Disease', 'start': 305, 'end': 337, 'mesh': 'D002340'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 416, 'end': 427, 'mesh': 'D002784'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 480, 'end': 491, 'mesh': 'D002784'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 524, 'end': 535, 'mesh': 'D002784'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 540, 'end': 551, 'mesh': 'D002784'}, {'text': 'gemfibrozil', 'type': 'Chemical', 'start': 603, 'end': 614, 'mesh': 'D015248'}, {'text': 'lovastatin', 'type': 'Chemical', 'start': 627, 'end': 637, 'mesh': 'D008148'}, {'text': 'creatine', 'type': 'Chemical', 'start': 847, 'end': 855, 'mesh': 'D003401'}, {'text': 'creatine', 'type': 'Chemical', 'start': 1039, 'end': 1047, 'mesh': 'D003401'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 1191, 'end': 1202, 'mesh': 'D002784'}, {'text': 'triglyceride', 'type': 'Chemical', 'start': 1240, 'end': 1252, 'mesh': 'D014280'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 1301, 'end': 1312, 'mesh': 'D002784'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 1364, 'end': 1375, 'mesh': 'D002784'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 1380, 'end': 1391, 'mesh': 'D002784'}, {'text': 'Myositis', 'type': 'Disease', 'start': 1465, 'end': 1473, 'mesh': 'D009220'}, {'text': 'creatine', 'type': 'Chemical', 'start': 1613, 'end': 1621, 'mesh': 'D003401'}, {'text': 'rhabdomyolysis', 'type': 'Disease', 'start': 1667, 'end': 1681, 'mesh': 'D012206'}, {'text': 'myoglobinuria', 'type': 'Disease', 'start': 1685, 'end': 1698, 'mesh': 'D009212'}]"
+1157,1655018,Hepatocellular carcinoma in Fanconi's anemia treated with androgen and corticosteroid.,"The case of an 11-year-old boy is reported who was known to have Fanconi's anemia for 3 years and was treated with androgens, corticosteroids and transfusions. Two weeks before his death he was readmitted because of aplastic crisis with septicemia and marked abnormalities in liver function and died of hemorrhagic bronchopneumonia. At autopsy peliosis and multiple hepatic tumors were found which histologically proved to be well-differentiated hepatocellular carcinoma. This case contributes to the previous observations that non-metastasizing hepatic neoplasms and peliosis can develop in patients with androgen- and corticosteroid-treated Fanconi's anemia.","[{'text': 'Hepatocellular carcinoma', 'type': 'Disease', 'start': 0, 'end': 24, 'mesh': 'D006528'}, {'text': ""Fanconi's anemia"", 'type': 'Disease', 'start': 28, 'end': 44, 'mesh': 'D005199'}, {'text': 'androgen', 'type': 'Chemical', 'start': 58, 'end': 66, 'mesh': 'D000728'}, {'text': 'corticosteroid', 'type': 'Chemical', 'start': 71, 'end': 85, 'mesh': 'D000305'}, {'text': ""Fanconi's anemia"", 'type': 'Disease', 'start': 152, 'end': 168, 'mesh': 'D005199'}, {'text': 'androgens', 'type': 'Chemical', 'start': 202, 'end': 211, 'mesh': 'D000728'}, {'text': 'corticosteroids', 'type': 'Chemical', 'start': 213, 'end': 228, 'mesh': 'D000305'}, {'text': 'septicemia', 'type': 'Disease', 'start': 324, 'end': 334, 'mesh': 'D018805'}, {'text': 'hemorrhagic bronchopneumonia', 'type': 'Disease', 'start': 390, 'end': 418, 'mesh': 'D001996'}, {'text': 'peliosis', 'type': 'Disease', 'start': 431, 'end': 439, 'mesh': 'D010382'}, {'text': 'hepatic tumors', 'type': 'Disease', 'start': 453, 'end': 467, 'mesh': 'D008113'}, {'text': 'hepatocellular carcinoma', 'type': 'Disease', 'start': 533, 'end': 557, 'mesh': 'D006528'}, {'text': 'hepatic neoplasms', 'type': 'Disease', 'start': 633, 'end': 650, 'mesh': 'D008113'}, {'text': 'peliosis', 'type': 'Disease', 'start': 655, 'end': 663, 'mesh': 'D010382'}, {'text': 'androgen', 'type': 'Chemical', 'start': 693, 'end': 701, 'mesh': 'D000728'}, {'text': 'corticosteroid', 'type': 'Chemical', 'start': 707, 'end': 721, 'mesh': 'D000305'}, {'text': ""Fanconi's anemia"", 'type': 'Disease', 'start': 730, 'end': 746, 'mesh': 'D005199'}]"
+1158,1735570,Chronic lesion of rostral ventrolateral medulla in spontaneously hypertensive rats.,"We studied the effects of chronic selective neuronal lesion of rostral ventrolateral medulla on mean arterial pressure, heart rate, and neurogenic tone in conscious, unrestrained spontaneously hypertensive rats. The lesions were placed via bilateral microinjections of 30 nmol/200 nl N-methyl-D-aspartic acid. The restimulation of this area with N-methyl-D-aspartic acid 15 days postlesion failed to produce a pressor response. One day postlesion, the resting mean arterial pressure was significantly decreased in lesioned rats when compared with sham rats (100 +/- 7 versus 173 +/- 4 mm Hg, p less than 0.05). Fifteen days later, the lesioned group still showed values significantly lower than the sham group (150 +/- 6 versus 167 +/- 5 mm Hg, p less than 0.05). No significant heart rate differences were observed between the sham and lesioned groups. The ganglionic blocker trimethaphan (5 mg/kg i.v.) caused similar reductions in mean arterial pressure in both lesioned and sham groups. The trimethaphan-induced hypotension was accompanied by a significant bradycardia in lesioned rats (-32 +/- 13 beats per minute) but a tachycardia in sham rats (+33 +/- 12 beats per minute) 1 day postlesion. Therefore, rostral ventrolateral medulla neurons appear to play a significant role in maintaining hypertension in conscious spontaneously hypertensive rats. Spinal or suprabulbar structures could be responsible for the gradual recovery of the hypertension in the lesioned rats.","[{'text': 'hypertensive', 'type': 'Disease', 'start': 65, 'end': 77, 'mesh': 'D006973'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 277, 'end': 289, 'mesh': 'D006973'}, {'text': 'N-methyl-D-aspartic acid', 'type': 'Chemical', 'start': 368, 'end': 392, 'mesh': 'D016202'}, {'text': 'N-methyl-D-aspartic acid', 'type': 'Chemical', 'start': 430, 'end': 454, 'mesh': 'D016202'}, {'text': 'trimethaphan', 'type': 'Chemical', 'start': 961, 'end': 973, 'mesh': 'D014294'}, {'text': 'trimethaphan', 'type': 'Chemical', 'start': 1079, 'end': 1091, 'mesh': 'D014294'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1100, 'end': 1111, 'mesh': 'D007022'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 1145, 'end': 1156, 'mesh': 'D001919'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 1210, 'end': 1221, 'mesh': 'D013610'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1381, 'end': 1393, 'mesh': 'D006973'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 1421, 'end': 1433, 'mesh': 'D006973'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1526, 'end': 1538, 'mesh': 'D006973'}]"
+1159,1756784,"Damage of substantia nigra pars reticulata during pilocarpine-induced status epilepticus in the rat: immunohistochemical study of neurons, astrocytes and serum-protein extravasation.","The substantia nigra has a gating function controlling the spread of epileptic seizure activity. Additionally, in models of prolonged status epilepticus the pars reticulata of substantia nigra (SNR) suffers from a massive lesion which may arise from a massive metabolic derangement and hyperexcitation developing in the activated SNR. In this study, status epilepticus was induced by systemic injection of pilocarpine in rats. The neuropathology of SNR was investigated using immunohistochemical techniques with the major emphasis on the time-course of changes in neurons and astrocytes. Animals surviving 20, 30, 40, 60 min, 2, 3, 6 hours, 1, 2, and 3 days after induction of status epilepticus were perfusion-fixed, and brains processed for immunohistochemical staining of SNR. Nissl-staining and antibodies against the neuron-specific calcium-binding protein, parvalbumin, served to detect neuronal damage in SNR. Antibodies against the astroglia-specific cytoskeletal protein, glial fibrillary acidic protein (GFAP), and against the glial calcium-binding protein, S-100 protein, were used to assess the status of astrocytes. Immunohistochemical staining for serum-albumin and immunoglobulins in brain tissue was taken as indicator of blood-brain barrier disturbances and vasogenic edema formation. Immunohistochemical staining indicated loss of GFAP-staining already at 30 min after induction of seizures in an oval focus situated in the center of SNR while sparing medial and lateral aspects. At 1 h there was additional vacuolation in S-100 protein staining. By 2 hours, parvalbumin-staining changed in the central SNR indicating neuronal damage, and Nissl-staining visualized some neuronal distortion. Staining for serum-proteins occurred in a patchy manner throughout the forebrain during the first hours. By 6 h, vasogenic edema covered the lesioned SNR. By 24 h, glial and neuronal markers indicated a massive lesion in the center of SNR. By 48-72 h, astrocytes surrounding the lesion increased in size, and polymorphic phagocytotic cells invaded the damaged area. In a further group of animals surviving 1 to 5 days, conventional paraffin-sections confirmed the neuronal and glial damage of SNR. Additional pathology of similar quality was found in the globus pallidus. Since astrocytes were always damaged in parallel with neurons in SNR it is proposed that the anatomical and functional interrelationship between neurons and astrocytes is particularly tight in SNR. Both cell elements may suffer in common from metabolic disturbance and neurotransmitter dysfunction as occur during massive status epilepticus.","[{'text': 'Damage of substantia nigra pars reticulata', 'type': 'Disease', 'start': 0, 'end': 42, 'mesh': 'D001930'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 50, 'end': 61, 'mesh': 'D010862'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 70, 'end': 88, 'mesh': 'D013226'}, {'text': 'epileptic seizure', 'type': 'Disease', 'start': 252, 'end': 269, 'mesh': 'D004827'}, {'text': 'prolonged status epilepticus', 'type': 'Disease', 'start': 307, 'end': 335, 'mesh': 'D013226'}, {'text': 'metabolic derangement', 'type': 'Disease', 'start': 443, 'end': 464, 'mesh': 'D008659'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 533, 'end': 551, 'mesh': 'D013226'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 589, 'end': 600, 'mesh': 'D010862'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 860, 'end': 878, 'mesh': 'D013226'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1021, 'end': 1028, 'mesh': 'D002118'}, {'text': 'neuronal damage', 'type': 'Disease', 'start': 1076, 'end': 1091, 'mesh': 'D009422'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1226, 'end': 1233, 'mesh': 'D002118'}, {'text': 'vasogenic edema', 'type': 'Disease', 'start': 1458, 'end': 1473, 'mesh': 'D001929'}, {'text': 'seizures', 'type': 'Disease', 'start': 1583, 'end': 1591, 'mesh': 'D012640'}, {'text': 'neuronal damage', 'type': 'Disease', 'start': 1819, 'end': 1834, 'mesh': 'D009422'}, {'text': 'vasogenic edema', 'type': 'Disease', 'start': 2005, 'end': 2020, 'mesh': 'D001929'}, {'text': 'lesioned SNR', 'type': 'Disease', 'start': 2033, 'end': 2045, 'mesh': 'D001930'}, {'text': 'damage of SNR', 'type': 'Disease', 'start': 2375, 'end': 2388, 'mesh': 'D001930'}, {'text': 'neurotransmitter dysfunction', 'type': 'Disease', 'start': 2733, 'end': 2761, 'mesh': 'D001480'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 2786, 'end': 2804, 'mesh': 'D013226'}]"
+1160,1760851,Reduced cardiotoxicity of doxorubicin given in the form of N-(2-hydroxypropyl)methacrylamide conjugates: and experimental study in the rat.,"A rat model was used to evaluate the general acute toxicity and the late cardiotoxicity of 4 mg/kg doxorubicin (DOX) given either as free drug or in the form of three N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates. In these HPMA copolymers, DOX was covalently bound via peptide linkages that were either non-biodegradable (Gly-Gly) or degradable by lysosomal proteinases (Gly-Phe-Leu-Gly). In addition, one biodegradable conjugate containing galactosamine was used; this residue was targeted to the liver. Over the first 3 weeks after the i.v. administration of free and polymer-bound DOX, all animals showed a transient reduction in body weight. However, the maximal reduction in body weight seen in animals that received polymer-bound DOX (4 mg/kg) was significantly lower than that observed in those that received free DOX (4 mg/kg) or a mixture of the unmodified parent HPMA copolymer and free DOX (4 mg/kg; P less than 0.01). Throughout the study (20 weeks), deaths related to cardiotoxicity were observed only in animals that received either free DOX or the mixture of HPMA copolymer and free DOX; in these cases, histological investigations revealed marked changes in the heart that were consistent with DOX-induced cardiotoxicity. Sequential measurements of cardiac output in surviving animals that received either free DOX or the mixture of HPMA copolymer and free DOX showed a reduction of approximately 30% in function beginning at the 4th week after drug administration. The heart rate in these animals was approximately 12% lower than that measured in age-matched control rats (P less than 0.05). Animals that were given the HPMA copolymer conjugates containing DOX exhibited no significant change in cardiac output throughout the study (P less than 0.05). In addition, no significant histological change was observed in the heart of animals that received DOX in the form of HPMA copolymer conjugates and were killed at the end of the study. However, these animals had shown a significant increase in heart rate beginning at 8 weeks after drug administration (P less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)","[{'text': 'cardiotoxicity', 'type': 'Disease', 'start': 8, 'end': 22, 'mesh': 'D066126'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 26, 'end': 37, 'mesh': 'D004317'}, {'text': 'N-(2-hydroxypropyl)methacrylamide', 'type': 'Chemical', 'start': 59, 'end': 92, 'mesh': 'C032976'}, {'text': 'toxicity', 'type': 'Disease', 'start': 191, 'end': 199, 'mesh': 'D064420'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 213, 'end': 227, 'mesh': 'D066126'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 239, 'end': 250, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 252, 'end': 255, 'mesh': 'D004317'}, {'text': 'N-(2-hydroxypropyl)methacrylamide', 'type': 'Chemical', 'start': 307, 'end': 340, 'mesh': 'C032976'}, {'text': 'HPMA', 'type': 'Chemical', 'start': 342, 'end': 346, 'mesh': 'C032976'}, {'text': 'HPMA', 'type': 'Chemical', 'start': 379, 'end': 383, 'mesh': 'C032976'}, {'text': 'DOX', 'type': 'Chemical', 'start': 396, 'end': 399, 'mesh': 'D004317'}, {'text': 'Gly-Phe-Leu-Gly', 'type': 'Chemical', 'start': 527, 'end': 542, 'mesh': 'C504380'}, {'text': 'galactosamine', 'type': 'Chemical', 'start': 597, 'end': 610, 'mesh': 'D005688'}, {'text': 'DOX', 'type': 'Chemical', 'start': 740, 'end': 743, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 892, 'end': 895, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 977, 'end': 980, 'mesh': 'D004317'}, {'text': 'HPMA', 'type': 'Chemical', 'start': 1029, 'end': 1033, 'mesh': 'C032976'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1053, 'end': 1056, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1137, 'end': 1151, 'mesh': 'D066126'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1208, 'end': 1211, 'mesh': 'D004317'}, {'text': 'HPMA', 'type': 'Chemical', 'start': 1230, 'end': 1234, 'mesh': 'C032976'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1254, 'end': 1257, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1366, 'end': 1369, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1378, 'end': 1392, 'mesh': 'D066126'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1483, 'end': 1486, 'mesh': 'D004317'}, {'text': 'HPMA', 'type': 'Chemical', 'start': 1505, 'end': 1509, 'mesh': 'C032976'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1529, 'end': 1532, 'mesh': 'D004317'}, {'text': 'HPMA', 'type': 'Chemical', 'start': 1793, 'end': 1797, 'mesh': 'C032976'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1830, 'end': 1833, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 2024, 'end': 2027, 'mesh': 'D004317'}, {'text': 'HPMA', 'type': 'Chemical', 'start': 2043, 'end': 2047, 'mesh': 'C032976'}]"
+1161,1779253,"Topical 0.025% capsaicin in chronic post-herpetic neuralgia: efficacy, predictors of response and long-term course.","In order to evaluate the efficacy, time-course of action and predictors of response to topical capsaicin, 39 patients with chronic post-herpetic neuralgia (PHN), median duration 24 months, were treated with 0.025% capsaicin cream for 8 weeks. During therapy the patients rated their pain on a visual analogue scale (VAS) and a verbal outcome scale. A follow-up investigation was performed 10-12 months after study onset on the patients who had improved. Nineteen patients (48.7%) substantially improved after the 8-week trial; 5 (12.8%) discontinued therapy due to side-effects such as intolerable capsaicin-induced burning sensations (4) or mastitis (1); 15 (38.5%) reported no benefit. The decrease in VAS ratings was significant after 2 weeks of continuous application. Of the responders 72.2% were still improved at the follow-up; only one-third of them had continued application irregularly. Treatment effect was not dependent on patient's age, duration or localization of PHN (trigeminal involvement was excluded), sensory disturbance or pain character. Treatment response was not correlated with the incidence, time-course or severity of capsaicin-induced burning. If confirmed in controlled trials, the long-term results of this open, non-randomized study might indicate that the analgesic effect of capsaicin in PHN is mediated by both interference with neuropeptide metabolism and morphological changes (perhaps degeneration) of nociceptive afferents.","[{'text': 'capsaicin', 'type': 'Chemical', 'start': 15, 'end': 24, 'mesh': 'D002211'}, {'text': 'post-herpetic neuralgia', 'type': 'Disease', 'start': 36, 'end': 59, 'mesh': 'D051474'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 211, 'end': 220, 'mesh': 'D002211'}, {'text': 'post-herpetic neuralgia', 'type': 'Disease', 'start': 247, 'end': 270, 'mesh': 'D051474'}, {'text': 'PHN', 'type': 'Disease', 'start': 272, 'end': 275, 'mesh': 'D051474'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 330, 'end': 339, 'mesh': 'D002211'}, {'text': 'pain', 'type': 'Disease', 'start': 399, 'end': 403, 'mesh': 'D010146'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 714, 'end': 723, 'mesh': 'D002211'}, {'text': 'mastitis', 'type': 'Disease', 'start': 758, 'end': 766, 'mesh': 'D008413'}, {'text': 'PHN', 'type': 'Disease', 'start': 1094, 'end': 1097, 'mesh': 'D051474'}, {'text': 'sensory disturbance', 'type': 'Disease', 'start': 1137, 'end': 1156, 'mesh': '-1'}, {'text': 'pain', 'type': 'Disease', 'start': 1160, 'end': 1164, 'mesh': 'D010146'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 1261, 'end': 1270, 'mesh': 'D002211'}, {'text': 'capsaicin', 'type': 'Chemical', 'start': 1424, 'end': 1433, 'mesh': 'D002211'}, {'text': 'PHN', 'type': 'Disease', 'start': 1437, 'end': 1440, 'mesh': 'D051474'}]"
+1162,1837756,"Serotonin reuptake inhibitors, paranoia, and the ventral basal ganglia.","Antidepressants have previously been associated with paranoid reactions in psychiatric patients. Five cases of paranoid exacerbation with the serotonin reuptake inhibitors fluoxetine and amitriptyline are reported here. Elements common to these cases included a history of paranoid symptomatology and the concomitant occurrence of depressive and psychotic symptoms. Complicated depressive disorders (including atypicality of course and symptomatology, chronicity, psychosis, bipolarity, and secondary onset in the course of a primary psychosis) may present particular vulnerability to paranoid exacerbations associated with serotonin reuptake inhibitors. Although the pharmacology and neurobiology of paranoia remain cryptic, several mechanisms, including 5HT3 receptor-mediated dopamine release, beta-noradrenergic receptor downregulation, or GABAB receptor upregulation acting in the vicinity of the ventral basal ganglia (possibly in lateral orbitofrontal or anterior cingulate circuits), might apply to this phenomenon. These cases call attention to possible paranoid exacerbations with serotonin reuptake blockers in select patients and raise neurobiological considerations regarding paranoia.","[{'text': 'Serotonin', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D012701'}, {'text': 'paranoia', 'type': 'Disease', 'start': 31, 'end': 39, 'mesh': 'D010259'}, {'text': 'paranoid', 'type': 'Disease', 'start': 125, 'end': 133, 'mesh': 'D010259'}, {'text': 'paranoid', 'type': 'Disease', 'start': 183, 'end': 191, 'mesh': 'D010259'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 214, 'end': 223, 'mesh': 'D012701'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 244, 'end': 254, 'mesh': 'D005473'}, {'text': 'amitriptyline', 'type': 'Chemical', 'start': 259, 'end': 272, 'mesh': 'D000639'}, {'text': 'paranoid', 'type': 'Disease', 'start': 345, 'end': 353, 'mesh': 'D010259'}, {'text': 'depressive disorders', 'type': 'Disease', 'start': 450, 'end': 470, 'mesh': 'D003866'}, {'text': 'psychosis', 'type': 'Disease', 'start': 536, 'end': 545, 'mesh': 'D011605'}, {'text': 'psychosis', 'type': 'Disease', 'start': 606, 'end': 615, 'mesh': 'D011605'}, {'text': 'paranoid', 'type': 'Disease', 'start': 657, 'end': 665, 'mesh': 'D010259'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 696, 'end': 705, 'mesh': 'D012701'}, {'text': 'paranoia', 'type': 'Disease', 'start': 773, 'end': 781, 'mesh': 'D010259'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 851, 'end': 859, 'mesh': 'D004298'}, {'text': 'paranoid', 'type': 'Disease', 'start': 1135, 'end': 1143, 'mesh': 'D010259'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 1163, 'end': 1172, 'mesh': 'D012701'}, {'text': 'paranoia', 'type': 'Disease', 'start': 1261, 'end': 1269, 'mesh': 'D010259'}]"
+1163,1858969,Five cases of encephalitis during treatment of loiasis with diethylcarbamazine.,"Five cases of encephalitis following treatment with diethylcarbamazine (DEC) were observed in Congolese patients with Loa loa filariasis. Two cases had a fatal outcome and one resulted in severe sequelae. The notable fact was that this complication occurred in three patients hospitalized before treatment began, with whom particularly strict therapeutic precautions were taken, i.e., initial dose less than 10 mg of DEC, very gradual dose increases, and associated anti-allergic treatment. This type of drug-induced complication may not be that uncommon in highly endemic regions. It occurs primarily, but not exclusively, in subjects presenting with a high microfilarial load. The relationship between the occurrence of encephalitis and the decrease in microfilaremia is evident. The pathophysiological mechanisms are discussed in the light of these observations and the few other comments on this subject published in the literature.","[{'text': 'encephalitis', 'type': 'Disease', 'start': 14, 'end': 26, 'mesh': 'D004660'}, {'text': 'loiasis', 'type': 'Disease', 'start': 47, 'end': 54, 'mesh': 'D008118'}, {'text': 'diethylcarbamazine', 'type': 'Chemical', 'start': 60, 'end': 78, 'mesh': 'D004049'}, {'text': 'encephalitis', 'type': 'Disease', 'start': 94, 'end': 106, 'mesh': 'D004660'}, {'text': 'diethylcarbamazine', 'type': 'Chemical', 'start': 132, 'end': 150, 'mesh': 'D004049'}, {'text': 'DEC', 'type': 'Chemical', 'start': 152, 'end': 155, 'mesh': 'D004049'}, {'text': 'filariasis', 'type': 'Disease', 'start': 206, 'end': 216, 'mesh': 'D005368'}, {'text': 'DEC', 'type': 'Chemical', 'start': 497, 'end': 500, 'mesh': 'D004049'}, {'text': 'encephalitis', 'type': 'Disease', 'start': 802, 'end': 814, 'mesh': 'D004660'}, {'text': 'microfilaremia', 'type': 'Disease', 'start': 835, 'end': 849, 'mesh': '-1'}]"
+1164,1905439,Delirium in an elderly woman possibly associated with administration of misoprostol.,"Misoprostol has been associated with adverse reactions, including gastrointestinal symptoms, gynecologic problems, and headache. Changes in mental status, however, have not been reported. We present a case in which an 89-year-old woman in a long-term care facility became confused after the initiation of misoprostol therapy. The patient's change in mental status was first reported nine days after the initiation of therapy. Her delirium significantly improved after misoprostol was discontinued and her mental status returned to normal within a week. Because no other factors related to this patient changed significantly, the delirium experienced by this patient possibly resulted from misoprostol therapy.","[{'text': 'Delirium', 'type': 'Disease', 'start': 0, 'end': 8, 'mesh': 'D003693'}, {'text': 'misoprostol', 'type': 'Chemical', 'start': 72, 'end': 83, 'mesh': 'D016595'}, {'text': 'Misoprostol', 'type': 'Chemical', 'start': 85, 'end': 96, 'mesh': 'D016595'}, {'text': 'headache', 'type': 'Disease', 'start': 204, 'end': 212, 'mesh': 'D006261'}, {'text': 'misoprostol', 'type': 'Chemical', 'start': 390, 'end': 401, 'mesh': 'D016595'}, {'text': 'delirium', 'type': 'Disease', 'start': 515, 'end': 523, 'mesh': 'D003693'}, {'text': 'misoprostol', 'type': 'Chemical', 'start': 553, 'end': 564, 'mesh': 'D016595'}, {'text': 'delirium', 'type': 'Disease', 'start': 714, 'end': 722, 'mesh': 'D003693'}, {'text': 'misoprostol', 'type': 'Chemical', 'start': 774, 'end': 785, 'mesh': 'D016595'}]"
+1165,1943082,Hepatocellular oxidant stress following intestinal ischemia-reperfusion injury.,"Reperfusion of ischemic intestine results in acute liver dysfunction characterized by hepatocellular enzyme release into plasma, reduction in bile flow rate, and neutrophil sequestration within the liver. The pathophysiology underlying this acute hepatic injury is unknown. This study was undertaken to determine whether oxidants are associated with the hepatic injury and to determine the relative value of several indirect methods of assessing oxidant exposure in vivo. Rats were subjected to a standardized intestinal ischemia-reperfusion injury. Hepatic tissue was assayed for lipid peroxidation products and oxidized and reduced glutathione. There was no change in hepatic tissue total glutathione following intestinal ischemia-reperfusion injury. Oxidized glutathione (GSSG) increased significantly following 30 and 60 min of reperfusion. There was no increase in any of the products of lipid peroxidation associated with this injury. An increase in GSSG within hepatic tissue during intestinal reperfusion suggests exposure of hepatocytes to an oxidant stress. The lack of a significant increase in products of lipid peroxidation suggests that the oxidant stress is of insufficient magnitude to result in irreversible injury to hepatocyte cell membranes. These data also suggest that the measurement of tissue GSSG may be a more sensitive indicator of oxidant stress than measurement of products of lipid peroxidation.","[{'text': 'ischemia', 'type': 'Disease', 'start': 51, 'end': 59, 'mesh': 'D007511'}, {'text': 'reperfusion injury', 'type': 'Disease', 'start': 60, 'end': 78, 'mesh': 'D015427'}, {'text': 'ischemic', 'type': 'Disease', 'start': 95, 'end': 103, 'mesh': 'D007511'}, {'text': 'liver dysfunction', 'type': 'Disease', 'start': 131, 'end': 148, 'mesh': 'D017093'}, {'text': 'hepatic injury', 'type': 'Disease', 'start': 327, 'end': 341, 'mesh': 'D056486'}, {'text': 'hepatic injury', 'type': 'Disease', 'start': 434, 'end': 448, 'mesh': 'D056486'}, {'text': 'ischemia', 'type': 'Disease', 'start': 601, 'end': 609, 'mesh': 'D007511'}, {'text': 'reperfusion injury', 'type': 'Disease', 'start': 610, 'end': 628, 'mesh': 'D015427'}, {'text': 'glutathione', 'type': 'Chemical', 'start': 771, 'end': 782, 'mesh': 'D005978'}, {'text': 'ischemia', 'type': 'Disease', 'start': 804, 'end': 812, 'mesh': 'D007511'}, {'text': 'reperfusion injury', 'type': 'Disease', 'start': 813, 'end': 831, 'mesh': 'D015427'}, {'text': 'Oxidized glutathione', 'type': 'Chemical', 'start': 833, 'end': 853, 'mesh': 'D019803'}, {'text': 'GSSG', 'type': 'Chemical', 'start': 855, 'end': 859, 'mesh': 'D019803'}, {'text': 'GSSG', 'type': 'Chemical', 'start': 1036, 'end': 1040, 'mesh': 'D019803'}, {'text': 'GSSG', 'type': 'Chemical', 'start': 1397, 'end': 1401, 'mesh': 'D019803'}]"
+1166,2021990,Diphenhydramine prevents the haemodynamic changes of cimetidine in ICU patients.,"Cimetidine, a histamine 2 (H2) antagonist, produces a decrease in arterial pressure due to vasodilatation, especially in critically ill patients. This may be because cimetidine acts as a histamine agonist. We, therefore, investigated the effects of the histamine 1(H1) receptor antagonist, diphenhydramine, on the haemodynamic changes observed after cimetidine in ICU patients. Each patient was studied on two separate days. In a random fashion, they received cimetidine 200 mg iv on one day, and on the other, a pretreatment of diphenhydramine 40 mg iv with cimetidine 200 mg iv. In the non-pretreatment group, mean arterial pressure (MAP) decreased from 107.4 +/- 8.4 mmHg to 86.7 +/- 11.4 mmHg (P less than 0.01) two minutes after cimetidine. Also, systemic vascular resistance (SVR) decreased during the eight-minute observation period (P less than 0.01). In contrast, in the pretreatment group, little haemodynamic change was seen. We conclude that an H1 antagonist may be useful in preventing hypotension caused by iv cimetidine, since the vasodilating activity of cimetidine is mediated, in part, through the H1 receptor.","[{'text': 'Diphenhydramine', 'type': 'Chemical', 'start': 0, 'end': 15, 'mesh': 'D004155'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 53, 'end': 63, 'mesh': 'D002927'}, {'text': 'Cimetidine', 'type': 'Chemical', 'start': 81, 'end': 91, 'mesh': 'D002927'}, {'text': 'histamine', 'type': 'Chemical', 'start': 95, 'end': 104, 'mesh': 'D006632'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 247, 'end': 257, 'mesh': 'D002927'}, {'text': 'histamine', 'type': 'Chemical', 'start': 268, 'end': 277, 'mesh': 'D006632'}, {'text': 'histamine', 'type': 'Chemical', 'start': 334, 'end': 343, 'mesh': 'D006632'}, {'text': 'diphenhydramine', 'type': 'Chemical', 'start': 371, 'end': 386, 'mesh': 'D004155'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 431, 'end': 441, 'mesh': 'D002927'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 541, 'end': 551, 'mesh': 'D002927'}, {'text': 'diphenhydramine', 'type': 'Chemical', 'start': 610, 'end': 625, 'mesh': 'D004155'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 640, 'end': 650, 'mesh': 'D002927'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 815, 'end': 825, 'mesh': 'D002927'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1080, 'end': 1091, 'mesh': 'D007022'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 1105, 'end': 1115, 'mesh': 'D002927'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 1152, 'end': 1162, 'mesh': 'D002927'}]"
+1167,2083961,Acute renal failure due to rifampicin.,"A 23-year-old male patient with bacteriologically proven pulmonary tuberculosis was treated with the various regimens of antituberculosis drugs for nearly 15 months. Rifampicin was administered thrice as one of the 3-4 drug regimen and each time he developed untoward side effects like nausea, vomiting and fever with chills and rigors. The last such episode was of acute renal failure at which stage the patient was seen by the authors of this report. The patient, however, made a full recovery.","[{'text': 'Acute renal failure', 'type': 'Disease', 'start': 0, 'end': 19, 'mesh': 'D058186'}, {'text': 'rifampicin', 'type': 'Chemical', 'start': 27, 'end': 37, 'mesh': 'D012293'}, {'text': 'pulmonary tuberculosis', 'type': 'Disease', 'start': 96, 'end': 118, 'mesh': 'D014397'}, {'text': 'Rifampicin', 'type': 'Chemical', 'start': 205, 'end': 215, 'mesh': 'D012293'}, {'text': 'nausea', 'type': 'Disease', 'start': 325, 'end': 331, 'mesh': 'D009325'}, {'text': 'vomiting', 'type': 'Disease', 'start': 333, 'end': 341, 'mesh': 'D014839'}, {'text': 'fever', 'type': 'Disease', 'start': 346, 'end': 351, 'mesh': 'D005334'}]"
+1168,2131034,Severe polyneuropathy and motor loss after intrathecal thiotepa combination chemotherapy: description of two cases.,"Two cases of severe delayed neurologic toxicity related to the administration of intrathecal (IT) combination chemotherapy including thiotepa (TSPA) are presented. Both cases developed axonal neuropathy with motor predominance in the lower extremities 1 and 6 months after IT chemotherapy was administered. Neurologic toxicities have been described with IT-methotrexate, IT-cytosine arabinoside and IT-TSPA. To our knowledge, however, axonal neuropathy following administration of these three agents has not been previously described. In spite of the fact that TSPA is a useful IT agent, its combination with MTX, ara-C and radiotherapy could cause severe neurotoxicity. This unexpected complication indicates the need for further toxicology research on IT-TSPA.","[{'text': 'polyneuropathy', 'type': 'Disease', 'start': 7, 'end': 21, 'mesh': 'D011115'}, {'text': 'thiotepa', 'type': 'Chemical', 'start': 55, 'end': 63, 'mesh': 'D013852'}, {'text': 'neurologic toxicity', 'type': 'Disease', 'start': 144, 'end': 163, 'mesh': 'D020258'}, {'text': 'thiotepa', 'type': 'Chemical', 'start': 249, 'end': 257, 'mesh': 'D013852'}, {'text': 'TSPA', 'type': 'Chemical', 'start': 259, 'end': 263, 'mesh': 'D013852'}, {'text': 'axonal neuropathy', 'type': 'Disease', 'start': 301, 'end': 318, 'mesh': 'D056768'}, {'text': 'Neurologic toxicities', 'type': 'Disease', 'start': 423, 'end': 444, 'mesh': 'D020258'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 473, 'end': 485, 'mesh': 'D008727'}, {'text': 'cytosine arabinoside', 'type': 'Chemical', 'start': 490, 'end': 510, 'mesh': 'D003561'}, {'text': 'TSPA', 'type': 'Chemical', 'start': 518, 'end': 522, 'mesh': 'D013852'}, {'text': 'axonal neuropathy', 'type': 'Disease', 'start': 551, 'end': 568, 'mesh': 'D056768'}, {'text': 'TSPA', 'type': 'Chemical', 'start': 677, 'end': 681, 'mesh': 'D013852'}, {'text': 'MTX', 'type': 'Chemical', 'start': 725, 'end': 728, 'mesh': 'D008727'}, {'text': 'ara-C', 'type': 'Chemical', 'start': 730, 'end': 735, 'mesh': 'D003561'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 772, 'end': 785, 'mesh': 'D020258'}, {'text': 'TSPA', 'type': 'Chemical', 'start': 873, 'end': 877, 'mesh': 'D013852'}]"
+1169,2173761,Effects of cromakalim and pinacidil on large epicardial and small coronary arteries in conscious dogs.,"The effects of i.v. bolus administration of cromakalim (1-10 micrograms/kg) and pinacidil (3-100 micrograms/kg) on large (circumflex artery) and small coronary arteries and on systemic hemodynamics were investigated in chronically instrumented conscious dogs and compared to those of nitroglycerin (0.03-10 micrograms/kg). Nitroglycerin, up to 0.3 micrograms/kg, selectively increased circumflex artery diameter (CxAD) without simultaneously affecting any other cardiac or systemic hemodynamic parameter. In contrast, cromakalim and pinacidil at all doses and nitroglycerin at doses higher than 0.3 micrograms/kg simultaneously and dose-dependently increased CxAD, coronary blood flow and heart rate and decreased coronary vascular resistance and aortic pressure. Cromakalim was approximately 8- to 9.5-fold more potent than pinacidil in increasing CxAD. Vasodilation of large and small coronary vessels and hypotension induced by cromakalim and pinacidil were not affected by prior combined beta adrenergic and muscarinic receptors blockade but drug-induced tachycardia was abolished. When circumflex artery blood flow was maintained constant, the increases in CxAD induced by cromakalim (10 micrograms/kg), pinacidil (30 micrograms/kg) and nitroglycerin (10 micrograms/kg) were reduced by 68 +/- 7, 54 +/- 9 and 1 +/- 1%, respectively. Thus, whereas nitroglycerin preferentially and flow-independently dilates large coronary arteries, cromakalim and pinacidil dilate both large and small coronary arteries and this effect is not dependent upon the simultaneous beta adrenoceptors-mediated rise in myocardial metabolic demand. Finally, two mechanisms at least, direct vasodilation and flow dependency, are involved in the cromakalim- and pinacidil-induced increase in CxAD.","[{'text': 'cromakalim', 'type': 'Chemical', 'start': 11, 'end': 21, 'mesh': 'D019806'}, {'text': 'pinacidil', 'type': 'Chemical', 'start': 26, 'end': 35, 'mesh': 'D020110'}, {'text': 'cromakalim', 'type': 'Chemical', 'start': 147, 'end': 157, 'mesh': 'D019806'}, {'text': 'pinacidil', 'type': 'Chemical', 'start': 183, 'end': 192, 'mesh': 'D020110'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 387, 'end': 400, 'mesh': 'D005996'}, {'text': 'Nitroglycerin', 'type': 'Chemical', 'start': 426, 'end': 439, 'mesh': 'D005996'}, {'text': 'cromakalim', 'type': 'Chemical', 'start': 621, 'end': 631, 'mesh': 'D019806'}, {'text': 'pinacidil', 'type': 'Chemical', 'start': 636, 'end': 645, 'mesh': 'D020110'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 663, 'end': 676, 'mesh': 'D005996'}, {'text': 'Cromakalim', 'type': 'Chemical', 'start': 867, 'end': 877, 'mesh': 'D019806'}, {'text': 'pinacidil', 'type': 'Chemical', 'start': 928, 'end': 937, 'mesh': 'D020110'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1011, 'end': 1022, 'mesh': 'D007022'}, {'text': 'cromakalim', 'type': 'Chemical', 'start': 1034, 'end': 1044, 'mesh': 'D019806'}, {'text': 'pinacidil', 'type': 'Chemical', 'start': 1049, 'end': 1058, 'mesh': 'D020110'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 1162, 'end': 1173, 'mesh': 'D013610'}, {'text': 'cromakalim', 'type': 'Chemical', 'start': 1281, 'end': 1291, 'mesh': 'D019806'}, {'text': 'pinacidil', 'type': 'Chemical', 'start': 1312, 'end': 1321, 'mesh': 'D020110'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 1345, 'end': 1358, 'mesh': 'D005996'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 1455, 'end': 1468, 'mesh': 'D005996'}, {'text': 'cromakalim', 'type': 'Chemical', 'start': 1540, 'end': 1550, 'mesh': 'D019806'}, {'text': 'pinacidil', 'type': 'Chemical', 'start': 1555, 'end': 1564, 'mesh': 'D020110'}, {'text': 'cromakalim', 'type': 'Chemical', 'start': 1826, 'end': 1836, 'mesh': 'D019806'}, {'text': 'pinacidil', 'type': 'Chemical', 'start': 1842, 'end': 1851, 'mesh': 'D020110'}]"
+1170,2217015,Mefenamic acid-induced neutropenia and renal failure in elderly females with hypothyroidism.,"We report mefenamic acid-induced non-oliguric renal failure and severe neutropenia occurring simultaneously in two elderly females. The neutropenia was due to maturation arrest of the myeloid series in one patient. Both patients were also hypothyroid, but it is not clear whether this was a predisposing factor to the development of these adverse reactions. However, it would seem prudent not to use mefenamic acid in hypothyroid patients until the hypothyroidism has been corrected.","[{'text': 'Mefenamic acid', 'type': 'Chemical', 'start': 0, 'end': 14, 'mesh': 'D008528'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 23, 'end': 34, 'mesh': 'D009503'}, {'text': 'renal failure', 'type': 'Disease', 'start': 39, 'end': 52, 'mesh': 'D051437'}, {'text': 'hypothyroidism', 'type': 'Disease', 'start': 77, 'end': 91, 'mesh': 'D007037'}, {'text': 'mefenamic acid', 'type': 'Chemical', 'start': 103, 'end': 117, 'mesh': 'D008528'}, {'text': 'renal failure', 'type': 'Disease', 'start': 139, 'end': 152, 'mesh': 'D051437'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 164, 'end': 175, 'mesh': 'D009503'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 229, 'end': 240, 'mesh': 'D009503'}, {'text': 'hypothyroid', 'type': 'Disease', 'start': 332, 'end': 343, 'mesh': 'D007037'}, {'text': 'mefenamic acid', 'type': 'Chemical', 'start': 493, 'end': 507, 'mesh': 'D008528'}, {'text': 'hypothyroid', 'type': 'Disease', 'start': 511, 'end': 522, 'mesh': 'D007037'}, {'text': 'hypothyroidism', 'type': 'Disease', 'start': 542, 'end': 556, 'mesh': 'D007037'}]"
+1171,2239937,Etiology of hypercalcemia in hemodialysis patients on calcium carbonate therapy.,"Fourteen of 39 dialysis patients (36%) became hypercalcemic after switching to calcium carbonate as their principal phosphate binder. In order to identify risk factors associated with the development of hypercalcemia, indirect parameters of intestinal calcium reabsorption and bone turnover rate in these 14 patients were compared with results in 14 eucalcemic patients matched for age, sex, length of time on dialysis, and etiology of renal disease. In addition to experiencing hypercalcemic episodes with peak calcium values of 2.7 to 3.8 mmol/L (10.7 to 15.0 mg/dL), patients in the hypercalcemic group exhibited a significant increase in the mean calcium concentration obtained during 6 months before the switch, compared with the mean value obtained during the 7 months of observation after the switch (2.4 +/- 0.03 to 2.5 +/- 0.03 mmol/L [9.7 +/- 0.2 to 10.2 +/- 0.1 mg/dL], P = 0.006). In contrast, eucalcemic patients exhibited no change in mean calcium values over the same time period (2.3 +/- 0.05 to 2.3 +/- 0.05 mmol/L [9.2 +/- 0.2 to 9.2 +/- 0.2 mg/dL]). CaCO3 dosage, calculated dietary calcium intake, and circulating levels of vitamin D metabolites were similar in both groups. Physical activity index and predialysis serum bicarbonate levels also were similar in both groups. However, there was a significant difference in parameters reflecting bone turnover rates between groups.(ABSTRACT TRUNCATED AT 250 WORDS)","[{'text': 'hypercalcemia', 'type': 'Disease', 'start': 12, 'end': 25, 'mesh': 'D006934'}, {'text': 'calcium carbonate', 'type': 'Chemical', 'start': 54, 'end': 71, 'mesh': 'D002119'}, {'text': 'hypercalcemic', 'type': 'Disease', 'start': 127, 'end': 140, 'mesh': 'D006934'}, {'text': 'calcium carbonate', 'type': 'Chemical', 'start': 160, 'end': 177, 'mesh': 'D002119'}, {'text': 'phosphate', 'type': 'Chemical', 'start': 197, 'end': 206, 'mesh': 'D010710'}, {'text': 'hypercalcemia', 'type': 'Disease', 'start': 284, 'end': 297, 'mesh': 'D006934'}, {'text': 'calcium', 'type': 'Chemical', 'start': 333, 'end': 340, 'mesh': 'D002118'}, {'text': 'renal disease', 'type': 'Disease', 'start': 517, 'end': 530, 'mesh': 'D007674'}, {'text': 'hypercalcemic', 'type': 'Disease', 'start': 560, 'end': 573, 'mesh': 'D006934'}, {'text': 'calcium', 'type': 'Chemical', 'start': 593, 'end': 600, 'mesh': 'D002118'}, {'text': 'hypercalcemic', 'type': 'Disease', 'start': 667, 'end': 680, 'mesh': 'D006934'}, {'text': 'calcium', 'type': 'Chemical', 'start': 732, 'end': 739, 'mesh': 'D002118'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1035, 'end': 1042, 'mesh': 'D002118'}, {'text': 'CaCO3', 'type': 'Chemical', 'start': 1150, 'end': 1155, 'mesh': 'D002119'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1183, 'end': 1190, 'mesh': 'D002118'}, {'text': 'vitamin D', 'type': 'Chemical', 'start': 1225, 'end': 1234, 'mesh': 'D014807'}, {'text': 'bicarbonate', 'type': 'Chemical', 'start': 1322, 'end': 1333, 'mesh': 'D001639'}]"
+1172,2320485,Methyldopa-induced hemolytic anemia in a 15 year old presenting as near-syncope.,"Methyldopa is an antihypertensive medication which is available generically and under the trade name Aldomet that is widely prescribed in the adult population and infrequently used in children. Methyldopa causes an autoimmune hemolytic anemia in a small percentage of patients who take the drug. We report a case of methyldopa-induced hemolytic anemia in a 15-year-old boy who presented to the emergency department with near-syncope. The boy had been treated with intravenous methyldopa during a trauma admission seven weeks prior to presentation. Evaluation revealed a hemoglobin of three grams, 3+ Coombs' test with polyspecific anti-human globulin and monospecific IgG reagents, and a warm reacting autoantibody. Transfusion and corticosteroid therapy resulted in a complete recovery of the patient. Emergency physicians treating children must be aware of this syndrome in order to diagnose and treat it correctly. A brief review of autoimmune and drug-induced hemolytic anemias is provided.","[{'text': 'Methyldopa', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D008750'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 19, 'end': 35, 'mesh': 'D000743'}, {'text': 'syncope', 'type': 'Disease', 'start': 72, 'end': 79, 'mesh': 'D013575'}, {'text': 'Methyldopa', 'type': 'Chemical', 'start': 81, 'end': 91, 'mesh': 'D008750'}, {'text': 'Aldomet', 'type': 'Chemical', 'start': 182, 'end': 189, 'mesh': 'D008750'}, {'text': 'Methyldopa', 'type': 'Chemical', 'start': 275, 'end': 285, 'mesh': 'D008750'}, {'text': 'autoimmune hemolytic anemia', 'type': 'Disease', 'start': 296, 'end': 323, 'mesh': 'D000744'}, {'text': 'methyldopa', 'type': 'Chemical', 'start': 397, 'end': 407, 'mesh': 'D008750'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 416, 'end': 432, 'mesh': 'D000743'}, {'text': 'emergency department', 'type': 'Disease', 'start': 475, 'end': 495, 'mesh': 'D004630'}, {'text': 'syncope', 'type': 'Disease', 'start': 506, 'end': 513, 'mesh': 'D013575'}, {'text': 'methyldopa', 'type': 'Chemical', 'start': 557, 'end': 567, 'mesh': 'D008750'}, {'text': 'trauma', 'type': 'Disease', 'start': 577, 'end': 583, 'mesh': 'D014947'}, {'text': 'corticosteroid', 'type': 'Chemical', 'start': 813, 'end': 827, 'mesh': 'D000305'}, {'text': 'hemolytic anemias', 'type': 'Disease', 'start': 1045, 'end': 1062, 'mesh': 'D000743'}]"
+1173,2358093,The long-term safety of danazol in women with hereditary angioedema.,"Although the short-term safety (less than or equal to 6 months) of danazol has been established in a variety of settings, no information exists as to its long-term safety. We therefore investigated the long-term safety of danazol by performing a retrospective chart review of 60 female patients with hereditary angioedema treated with danazol for a continuous period of 6 months or longer. The mean age of the patients was 35.2 years and the mean duration of therapy was 59.7 months. Virtually all patients experienced one or more adverse reactions. Menstrual abnormalities (79%), weight gain (60%), muscle cramps/myalgias (40%), and transaminase elevations (40%) were the most common adverse reactions. The drug was discontinued due to adverse reactions in 8 patients. No patient has died or suffered any apparent long-term sequelae that were directly attributable to the drug. We conclude that, despite a relatively high incidence of adverse reactions, danazol has proven to be remarkably safe over the long-term in this group of patients.","[{'text': 'danazol', 'type': 'Chemical', 'start': 24, 'end': 31, 'mesh': 'D003613'}, {'text': 'hereditary angioedema', 'type': 'Disease', 'start': 46, 'end': 67, 'mesh': 'D054179'}, {'text': 'danazol', 'type': 'Chemical', 'start': 136, 'end': 143, 'mesh': 'D003613'}, {'text': 'danazol', 'type': 'Chemical', 'start': 291, 'end': 298, 'mesh': 'D003613'}, {'text': 'hereditary angioedema', 'type': 'Disease', 'start': 369, 'end': 390, 'mesh': 'D054179'}, {'text': 'danazol', 'type': 'Chemical', 'start': 404, 'end': 411, 'mesh': 'D003613'}, {'text': 'Menstrual abnormalities', 'type': 'Disease', 'start': 619, 'end': 642, 'mesh': 'D008599'}, {'text': 'weight gain', 'type': 'Disease', 'start': 650, 'end': 661, 'mesh': 'D015430'}, {'text': 'muscle cramps', 'type': 'Disease', 'start': 669, 'end': 682, 'mesh': 'D009120'}, {'text': 'myalgias', 'type': 'Disease', 'start': 683, 'end': 691, 'mesh': 'D063806'}, {'text': 'danazol', 'type': 'Chemical', 'start': 1024, 'end': 1031, 'mesh': 'D003613'}]"
+1174,2383364,Patient tolerance study of topical chlorhexidine diphosphanilate: a new topical agent for burns.,"Effective topical antimicrobial agents decrease infection and mortality in burn patients. Chlorhexidine phosphanilate (CHP), a new broad-spectrum antimicrobial agent, has been evaluated as a topical burn wound dressing in cream form, but preliminary clinical trials reported that it was painful upon application. This study compared various concentrations of CHP to determine if a tolerable concentration could be identified with retention of antimicrobial efficacy. Twenty-nine burn patients, each with two similar burns which could be separately treated, were given pairs of treatments at successive 12-h intervals over a 3-day period. One burn site was treated with each of four different CHP concentrations, from 0.25 per cent to 2 per cent, their vehicle, and 1 per cent silver sulphadiazine (AgSD) cream, an antimicrobial agent frequently used for topical treatment of burn wounds. The other site was always treated with AgSD cream. There was a direct relationship between CHP concentration and patients' ratings of pain on an analogue scale. The 0.25 per cent CHP cream was closest to AgSD in pain tolerance; however, none of the treatments differed statistically from AgSD or from each other. In addition, ease of application of CHP creams was less satisfactory than that of AgSD. It was concluded that formulations at or below 0.5 per cent CHP may prove acceptable for wound care, but the vehicle system needs pharmaceutical improvement to render it more tolerable and easier to use.","[{'text': 'chlorhexidine diphosphanilate', 'type': 'Chemical', 'start': 35, 'end': 64, 'mesh': 'C048279'}, {'text': 'burns', 'type': 'Disease', 'start': 90, 'end': 95, 'mesh': 'D002056'}, {'text': 'infection', 'type': 'Disease', 'start': 145, 'end': 154, 'mesh': 'D007239'}, {'text': 'burn', 'type': 'Disease', 'start': 172, 'end': 176, 'mesh': 'D002056'}, {'text': 'Chlorhexidine phosphanilate', 'type': 'Chemical', 'start': 187, 'end': 214, 'mesh': 'C048279'}, {'text': 'CHP', 'type': 'Chemical', 'start': 216, 'end': 219, 'mesh': 'C048279'}, {'text': 'burn', 'type': 'Disease', 'start': 296, 'end': 300, 'mesh': 'D002056'}, {'text': 'CHP', 'type': 'Chemical', 'start': 456, 'end': 459, 'mesh': 'C048279'}, {'text': 'burn', 'type': 'Disease', 'start': 576, 'end': 580, 'mesh': 'D002056'}, {'text': 'burns', 'type': 'Disease', 'start': 613, 'end': 618, 'mesh': 'D002056'}, {'text': 'burn', 'type': 'Disease', 'start': 739, 'end': 743, 'mesh': 'D002056'}, {'text': 'CHP', 'type': 'Chemical', 'start': 789, 'end': 792, 'mesh': 'C048279'}, {'text': 'silver sulphadiazine', 'type': 'Chemical', 'start': 873, 'end': 893, 'mesh': 'D012837'}, {'text': 'AgSD', 'type': 'Chemical', 'start': 895, 'end': 899, 'mesh': 'D012837'}, {'text': 'burn', 'type': 'Disease', 'start': 972, 'end': 976, 'mesh': 'D002056'}, {'text': 'AgSD', 'type': 'Chemical', 'start': 1024, 'end': 1028, 'mesh': 'D012837'}, {'text': 'CHP', 'type': 'Chemical', 'start': 1076, 'end': 1079, 'mesh': 'C048279'}, {'text': 'pain', 'type': 'Disease', 'start': 1119, 'end': 1123, 'mesh': 'D010146'}, {'text': 'CHP', 'type': 'Chemical', 'start': 1164, 'end': 1167, 'mesh': 'C048279'}, {'text': 'AgSD', 'type': 'Chemical', 'start': 1189, 'end': 1193, 'mesh': 'D012837'}, {'text': 'pain', 'type': 'Disease', 'start': 1197, 'end': 1201, 'mesh': 'D010146'}, {'text': 'AgSD', 'type': 'Chemical', 'start': 1273, 'end': 1277, 'mesh': 'D012837'}, {'text': 'CHP', 'type': 'Chemical', 'start': 1334, 'end': 1337, 'mesh': 'C048279'}, {'text': 'AgSD', 'type': 'Chemical', 'start': 1380, 'end': 1384, 'mesh': 'D012837'}, {'text': 'CHP', 'type': 'Chemical', 'start': 1446, 'end': 1449, 'mesh': 'C048279'}]"
+1175,2400986,Dose-dependent neurotoxicity of high-dose busulfan in children: a clinical and pharmacological study.,"Busulfan is known to be neurotoxic in animals and humans, but its acute neurotoxicity remains poorly characterized in children. We report here a retrospective study of 123 children (median age, 6.5 years) receiving high-dose busulfan in combined chemotherapy before bone marrow transplantation for malignant solid tumors, brain tumors excluded. Busulfan was given p.o., every 6 hours for 16 doses over 4 days. Two total doses were consecutively used: 16 mg/kg, then 600 mg/m2. The dose calculation on the basis of body surface area results in higher doses in young children than in older patients (16 to 28 mg/kg). Ninety-six patients were not given anticonvulsive prophylaxis; 7 (7.5%) developed seizures during the 4 days of the busulfan course or within 24 h after the last dosing. When the total busulfan dose was taken into account, there was a significant difference in terms of neurotoxicity incidence among patients under 16 mg/kg (1 of 57, 1.7%) and patients under 600 mg/m2 (6 of 39, 15.4%) (P less than 0.02). Twenty-seven patients were given a 600-mg/m2 busulfan total dose with continuous i.v. infusion of clonazepam; none had any neurological symptoms. Busulfan levels were measured by a gas chromatographic-mass spectrometry assay in the plasma and cerebrospinal fluid of 9 children without central nervous system disease under 600 mg/m2 busulfan with clonazepam:busulfan cerebrospinal fluid:plasma ratio was 1.39. This was significantly different (P less than 0.02) from the cerebrospinal fluid:plasma ratio previously defined in children receiving a 16-mg/kg total dose of busulfan. This study shows that busulfan neurotoxicity is dose-dependent in children and efficiently prevented by clonazepam. A busulfan dose calculated on the basis of body surface area, resulting in higher doses in young children, was followed by increased neurotoxicity, close to neurotoxicity incidence observed in adults. Since plasma pharmacokinetic studies showed a faster busulfan clearance in children than in adults, this new dose may approximate more closely the adult systemic exposure obtained after the usual 16-mg/kg total dose, with potential inferences in terms of anticancer or myeloablative effects. The busulfan dose in children and infants undergoing bone marrow transplantation should be reconsidered on the basis of pharmacokinetic studies.","[{'text': 'neurotoxicity', 'type': 'Disease', 'start': 15, 'end': 28, 'mesh': 'D020258'}, {'text': 'busulfan', 'type': 'Chemical', 'start': 42, 'end': 50, 'mesh': 'D002066'}, {'text': 'Busulfan', 'type': 'Chemical', 'start': 102, 'end': 110, 'mesh': 'D002066'}, {'text': 'neurotoxic', 'type': 'Disease', 'start': 126, 'end': 136, 'mesh': 'D020258'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 174, 'end': 187, 'mesh': 'D020258'}, {'text': 'busulfan', 'type': 'Chemical', 'start': 327, 'end': 335, 'mesh': 'D002066'}, {'text': 'tumors', 'type': 'Disease', 'start': 416, 'end': 422, 'mesh': 'D009369'}, {'text': 'brain tumors', 'type': 'Disease', 'start': 424, 'end': 436, 'mesh': 'D001932'}, {'text': 'Busulfan', 'type': 'Chemical', 'start': 447, 'end': 455, 'mesh': 'D002066'}, {'text': 'seizures', 'type': 'Disease', 'start': 799, 'end': 807, 'mesh': 'D012640'}, {'text': 'busulfan', 'type': 'Chemical', 'start': 833, 'end': 841, 'mesh': 'D002066'}, {'text': 'busulfan', 'type': 'Chemical', 'start': 902, 'end': 910, 'mesh': 'D002066'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 987, 'end': 1000, 'mesh': 'D020258'}, {'text': 'busulfan', 'type': 'Chemical', 'start': 1168, 'end': 1176, 'mesh': 'D002066'}, {'text': 'clonazepam', 'type': 'Chemical', 'start': 1221, 'end': 1231, 'mesh': 'D002998'}, {'text': 'neurological symptoms', 'type': 'Disease', 'start': 1246, 'end': 1267, 'mesh': 'D009461'}, {'text': 'Busulfan', 'type': 'Chemical', 'start': 1269, 'end': 1277, 'mesh': 'D002066'}, {'text': 'central nervous system disease', 'type': 'Disease', 'start': 1408, 'end': 1438, 'mesh': 'D002493'}, {'text': 'busulfan', 'type': 'Chemical', 'start': 1455, 'end': 1463, 'mesh': 'D002066'}, {'text': 'clonazepam', 'type': 'Chemical', 'start': 1469, 'end': 1479, 'mesh': 'D002998'}, {'text': 'busulfan', 'type': 'Chemical', 'start': 1480, 'end': 1488, 'mesh': 'D002066'}, {'text': 'busulfan', 'type': 'Chemical', 'start': 1692, 'end': 1700, 'mesh': 'D002066'}, {'text': 'busulfan', 'type': 'Chemical', 'start': 1724, 'end': 1732, 'mesh': 'D002066'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 1733, 'end': 1746, 'mesh': 'D020258'}, {'text': 'clonazepam', 'type': 'Chemical', 'start': 1806, 'end': 1816, 'mesh': 'D002998'}, {'text': 'busulfan', 'type': 'Chemical', 'start': 1820, 'end': 1828, 'mesh': 'D002066'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 1951, 'end': 1964, 'mesh': 'D020258'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 1975, 'end': 1988, 'mesh': 'D020258'}, {'text': 'busulfan', 'type': 'Chemical', 'start': 2072, 'end': 2080, 'mesh': 'D002066'}, {'text': 'busulfan', 'type': 'Chemical', 'start': 2315, 'end': 2323, 'mesh': 'D002066'}]"
+1176,2429800,Histamine antagonists and d-tubocurarine-induced hypotension in cardiac surgical patients.,"Hemodynamic effects and histamine release by bolus injection of 0.35 mg/kg of d-tubocurarine were studied in 24 patients. H1- and H2-histamine antagonists or placebo were given before dosing with d-tubocurarine in a randomized double-blind fashion to four groups: group 1--placebo; group 2--cimetidine, 4 mg/kg, plus placebo; group 3--chlorpheniramine, 0.1 mg/kg, plus placebo; and group 4--cimetidine plus chlorpheniramine. Histamine release occurred in most patients, the highest level 2 minutes after d-tubocurarine dosing. Group 1 had a moderate negative correlation between plasma histamine change and systemic vascular resistance (r = 0.58; P less than 0.05) not present in group 4. Prior dosing with antagonists partially prevented the fall in systemic vascular resistance. These data demonstrate that the hemodynamic changes associated with d-tubocurarine dosing are only partially explained by histamine release. Thus prior dosing with H1- and H2-antagonists provides only partial protection.","[{'text': 'Histamine', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D006632'}, {'text': 'd-tubocurarine', 'type': 'Chemical', 'start': 26, 'end': 40, 'mesh': 'D014403'}, {'text': 'hypotension', 'type': 'Disease', 'start': 49, 'end': 60, 'mesh': 'D007022'}, {'text': 'histamine', 'type': 'Chemical', 'start': 115, 'end': 124, 'mesh': 'D006632'}, {'text': 'd-tubocurarine', 'type': 'Chemical', 'start': 169, 'end': 183, 'mesh': 'D014403'}, {'text': 'histamine', 'type': 'Chemical', 'start': 224, 'end': 233, 'mesh': 'D006632'}, {'text': 'd-tubocurarine', 'type': 'Chemical', 'start': 287, 'end': 301, 'mesh': 'D014403'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 382, 'end': 392, 'mesh': 'D002927'}, {'text': 'chlorpheniramine', 'type': 'Chemical', 'start': 426, 'end': 442, 'mesh': 'D002744'}, {'text': 'cimetidine', 'type': 'Chemical', 'start': 482, 'end': 492, 'mesh': 'D002927'}, {'text': 'chlorpheniramine', 'type': 'Chemical', 'start': 498, 'end': 514, 'mesh': 'D002744'}, {'text': 'Histamine', 'type': 'Chemical', 'start': 516, 'end': 525, 'mesh': 'D006632'}, {'text': 'd-tubocurarine', 'type': 'Chemical', 'start': 595, 'end': 609, 'mesh': 'D014403'}, {'text': 'histamine', 'type': 'Chemical', 'start': 677, 'end': 686, 'mesh': 'D006632'}, {'text': 'd-tubocurarine', 'type': 'Chemical', 'start': 940, 'end': 954, 'mesh': 'D014403'}, {'text': 'histamine', 'type': 'Chemical', 'start': 994, 'end': 1003, 'mesh': 'D006632'}]"
+1177,2453942,Convulsant effect of lindane and regional brain concentration of GABA and dopamine.,"Lindane (gamma-hexachlorocyclohexane) is an organochlorine insecticide with known neurotoxic effects. Its mechanism of action is not well understood although it has been proposed that lindane acts as a non-competitive antagonist at the gamma-aminobutyric acid (GABA)-A receptor. We studied the effect of lindane (150 mg/kg) on the GABAergic and dopaminergic systems by measuring the concentration of GABA, dopamine and its metabolites in 7 brain areas at the onset of seizures. All animals suffered tonic convulsions at 18.3 +/- 1.4 min after lindane administration. The concentration of GABA was only slightly but significantly decreased in the colliculi without modifications in the other areas. The concentration of dopamine was increased in the mesencephalon and that of its metabolite DOPAC was also increased in the mesencephalon and the striatum.","[{'text': 'lindane', 'type': 'Chemical', 'start': 21, 'end': 28, 'mesh': 'D001556'}, {'text': 'GABA', 'type': 'Chemical', 'start': 65, 'end': 69, 'mesh': 'D005680'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 74, 'end': 82, 'mesh': 'D004298'}, {'text': 'Lindane', 'type': 'Chemical', 'start': 84, 'end': 91, 'mesh': 'D001556'}, {'text': 'gamma-hexachlorocyclohexane', 'type': 'Chemical', 'start': 93, 'end': 120, 'mesh': 'D001556'}, {'text': 'neurotoxic', 'type': 'Disease', 'start': 166, 'end': 176, 'mesh': 'D020258'}, {'text': 'lindane', 'type': 'Chemical', 'start': 268, 'end': 275, 'mesh': 'D001556'}, {'text': 'gamma-aminobutyric acid', 'type': 'Chemical', 'start': 320, 'end': 343, 'mesh': 'D005680'}, {'text': 'GABA', 'type': 'Chemical', 'start': 345, 'end': 349, 'mesh': 'D005680'}, {'text': 'lindane', 'type': 'Chemical', 'start': 388, 'end': 395, 'mesh': 'D001556'}, {'text': 'GABA', 'type': 'Chemical', 'start': 484, 'end': 488, 'mesh': 'D005680'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 490, 'end': 498, 'mesh': 'D004298'}, {'text': 'seizures', 'type': 'Disease', 'start': 552, 'end': 560, 'mesh': 'D012640'}, {'text': 'convulsions', 'type': 'Disease', 'start': 589, 'end': 600, 'mesh': 'D012640'}, {'text': 'lindane', 'type': 'Chemical', 'start': 627, 'end': 634, 'mesh': 'D001556'}, {'text': 'GABA', 'type': 'Chemical', 'start': 672, 'end': 676, 'mesh': 'D005680'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 803, 'end': 811, 'mesh': 'D004298'}, {'text': 'DOPAC', 'type': 'Chemical', 'start': 874, 'end': 879, 'mesh': 'D015102'}]"
+1178,2484903,Unusual complications of antithyroid drug therapy: four case reports and review of literature.,"Two cases of propylthiouracil-associated acute hepatitis, one case of fatal methimazole-associated hepatocellular necrosis and one case of propylthiouracil-associated lupus-like syndrome are described. The literature related to antithyroid drug side effects and the mechanisms for their occurrence are reviewed and the efficacy and complications of thyroidectomy and radioiodine compared to those of antithyroid drugs. It is concluded that in most circumstances 131I is the therapy of choice for hyperthyroidism.","[{'text': 'propylthiouracil', 'type': 'Chemical', 'start': 108, 'end': 124, 'mesh': 'D011441'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 142, 'end': 151, 'mesh': 'D056486'}, {'text': 'methimazole', 'type': 'Chemical', 'start': 171, 'end': 182, 'mesh': 'D008713'}, {'text': 'hepatocellular necrosis', 'type': 'Disease', 'start': 194, 'end': 217, 'mesh': 'D047508'}, {'text': 'propylthiouracil', 'type': 'Chemical', 'start': 234, 'end': 250, 'mesh': 'D011441'}, {'text': 'lupus-like syndrome', 'type': 'Disease', 'start': 262, 'end': 281, 'mesh': 'D008180'}, {'text': 'hyperthyroidism', 'type': 'Disease', 'start': 591, 'end': 606, 'mesh': 'D006980'}]"
+1179,2553470,Anticonvulsant actions of MK-801 on the lithium-pilocarpine model of status epilepticus in rats.,"MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, was tested for anticonvulsant effects in rats using two seizure models, coadministration of lithium and pilocarpine and administration of a high dose of pilocarpine alone. Three major results are reported. First, pretreatment with MK-801 produced an effective and dose-dependent anticonvulsant action with the lithium-pilocarpine model but not with rats treated with pilocarpine alone, suggesting that different biochemical mechanisms control seizures in these two models. Second, the anticonvulsant effect of MK-801 in the lithium-pilocarpine model only occurred after initial periods of seizure activity. This observation is suggested to be an in vivo demonstration of the conclusion derived from in vitro experiments that MK-801 binding requires agonist-induced opening of the channel sites of the NMDA receptor. Third, although it is relatively easy to block seizures induced by lithium and pilocarpine by administration of anticonvulsants prior to pilocarpine, it is more difficult to terminate ongoing status epilepticus and block the lethality of the seizures. Administration of MK-801 30 or 60 min after pilocarpine, i.e., during status epilepticus, gradually reduced electrical and behavioral seizure activity and greatly enhanced the survival rate. These results suggest that activation of NMDA receptors plays an important role in status epilepticus and brain damage in the lithium-pilocarpine model. This was further supported by results showing that nonconvulsive doses of NMDA and pilocarpine were synergistic, resulting in status epilepticus and subsequent mortality.","[{'text': 'MK-801', 'type': 'Chemical', 'start': 26, 'end': 32, 'mesh': 'D016291'}, {'text': 'lithium', 'type': 'Chemical', 'start': 40, 'end': 47, 'mesh': 'D008094'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 48, 'end': 59, 'mesh': 'D010862'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 69, 'end': 87, 'mesh': 'D013226'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 97, 'end': 103, 'mesh': 'D016291'}, {'text': 'N-methyl-D-aspartate', 'type': 'Chemical', 'start': 122, 'end': 142, 'mesh': 'D016202'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 144, 'end': 148, 'mesh': 'D016202'}, {'text': 'seizure', 'type': 'Disease', 'start': 227, 'end': 234, 'mesh': 'D012640'}, {'text': 'lithium', 'type': 'Chemical', 'start': 263, 'end': 270, 'mesh': 'D008094'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 275, 'end': 286, 'mesh': 'D010862'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 324, 'end': 335, 'mesh': 'D010862'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 402, 'end': 408, 'mesh': 'D016291'}, {'text': 'lithium', 'type': 'Chemical', 'start': 481, 'end': 488, 'mesh': 'D008094'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 489, 'end': 500, 'mesh': 'D010862'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 538, 'end': 549, 'mesh': 'D010862'}, {'text': 'seizures', 'type': 'Disease', 'start': 614, 'end': 622, 'mesh': 'D012640'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 681, 'end': 687, 'mesh': 'D016291'}, {'text': 'lithium', 'type': 'Chemical', 'start': 695, 'end': 702, 'mesh': 'D008094'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 703, 'end': 714, 'mesh': 'D010862'}, {'text': 'seizure', 'type': 'Disease', 'start': 760, 'end': 767, 'mesh': 'D012640'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 896, 'end': 902, 'mesh': 'D016291'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 972, 'end': 976, 'mesh': 'D016202'}, {'text': 'seizures', 'type': 'Disease', 'start': 1034, 'end': 1042, 'mesh': 'D012640'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1054, 'end': 1061, 'mesh': 'D008094'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1066, 'end': 1077, 'mesh': 'D010862'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1124, 'end': 1135, 'mesh': 'D010862'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 1179, 'end': 1197, 'mesh': 'D013226'}, {'text': 'seizures', 'type': 'Disease', 'start': 1229, 'end': 1237, 'mesh': 'D012640'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 1257, 'end': 1263, 'mesh': 'D016291'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1283, 'end': 1294, 'mesh': 'D010862'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 1309, 'end': 1327, 'mesh': 'D013226'}, {'text': 'seizure', 'type': 'Disease', 'start': 1373, 'end': 1380, 'mesh': 'D012640'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 1471, 'end': 1475, 'mesh': 'D016202'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 1513, 'end': 1531, 'mesh': 'D013226'}, {'text': 'brain damage', 'type': 'Disease', 'start': 1536, 'end': 1548, 'mesh': 'D001930'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1556, 'end': 1563, 'mesh': 'D008094'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1564, 'end': 1575, 'mesh': 'D010862'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 1657, 'end': 1661, 'mesh': 'D016202'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1666, 'end': 1677, 'mesh': 'D010862'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 1709, 'end': 1727, 'mesh': 'D013226'}]"
+1180,2614930,Nifedipine induced bradycardia in a patient with autonomic neuropathy.,"An 80 year old diabetic male with evidence of peripheral and autonomic neuropathy was admitted with chest pain. He was found to have atrial flutter at a ventricular rate of 70/min which slowed down to 30-40/min when nifedipine (60 mg) in 3 divided doses, during which he was paced at a rate of 70/min. This is inconsistent with the well-established finding that nifedipine induces tachycardia in normally innervated hearts. However, in hearts deprived of compensatory sympathetic drive, it may lead to bradycardia.","[{'text': 'Nifedipine', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D009543'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 19, 'end': 30, 'mesh': 'D001919'}, {'text': 'autonomic neuropathy', 'type': 'Disease', 'start': 49, 'end': 69, 'mesh': 'D009422'}, {'text': 'diabetic', 'type': 'Disease', 'start': 86, 'end': 94, 'mesh': 'D003920'}, {'text': 'chest pain', 'type': 'Disease', 'start': 171, 'end': 181, 'mesh': 'D002637'}, {'text': 'atrial flutter', 'type': 'Disease', 'start': 204, 'end': 218, 'mesh': 'D001282'}, {'text': 'nifedipine', 'type': 'Chemical', 'start': 287, 'end': 297, 'mesh': 'D009543'}, {'text': 'nifedipine', 'type': 'Chemical', 'start': 433, 'end': 443, 'mesh': 'D009543'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 452, 'end': 463, 'mesh': 'D013610'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 573, 'end': 584, 'mesh': 'D001919'}]"
+1181,2625524,The effect of haloperidol in cocaine and amphetamine intoxication.,"The effectiveness of haloperidol pretreatment in preventing the toxic effects of high doses of amphetamine and cocaine was studied in rats. In this model, toxic effects were induced by intraperitoneal (i.p.) injection of amphetamine 75 mg/kg (100% death rate) or cocaine 70 mg/kg (82% death rate). Haloperidol failed to prevent amphetamine-induced seizures, but did lower the mortality rate at most doses tested. Haloperidol decreased the incidence of cocaine-induced seizures at the two highest doses, but the lowering of the mortality rate did not reach statistical significance at any dose. These data suggest a protective role for the central dopamine blocker haloperidol against death from high-dose amphetamine exposure without reducing the incidence of seizures. In contrast, haloperidol demonstrated an ability to reduce cocaine-induced seizures without significantly reducing mortality.","[{'text': 'haloperidol', 'type': 'Chemical', 'start': 14, 'end': 25, 'mesh': 'D006220'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 29, 'end': 36, 'mesh': 'D003042'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 41, 'end': 52, 'mesh': 'D000661'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 88, 'end': 99, 'mesh': 'D006220'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 162, 'end': 173, 'mesh': 'D000661'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 178, 'end': 185, 'mesh': 'D003042'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 288, 'end': 299, 'mesh': 'D000661'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 330, 'end': 337, 'mesh': 'D003042'}, {'text': 'Haloperidol', 'type': 'Chemical', 'start': 365, 'end': 376, 'mesh': 'D006220'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 395, 'end': 406, 'mesh': 'D000661'}, {'text': 'seizures', 'type': 'Disease', 'start': 415, 'end': 423, 'mesh': 'D012640'}, {'text': 'Haloperidol', 'type': 'Chemical', 'start': 480, 'end': 491, 'mesh': 'D006220'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 519, 'end': 526, 'mesh': 'D003042'}, {'text': 'seizures', 'type': 'Disease', 'start': 535, 'end': 543, 'mesh': 'D012640'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 714, 'end': 722, 'mesh': 'D004298'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 731, 'end': 742, 'mesh': 'D006220'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 772, 'end': 783, 'mesh': 'D000661'}, {'text': 'seizures', 'type': 'Disease', 'start': 827, 'end': 835, 'mesh': 'D012640'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 850, 'end': 861, 'mesh': 'D006220'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 896, 'end': 903, 'mesh': 'D003042'}, {'text': 'seizures', 'type': 'Disease', 'start': 912, 'end': 920, 'mesh': 'D012640'}]"
+1182,2650911,Autoradiographic evidence of estrogen binding sites in nuclei of diethylstilbesterol induced hamster renal carcinomas.,"Estrogen binding sites were demonstrated by autoradiography in one transplantable and five primary diethylstilbesterol induced renal carcinomas in three hamsters. Radiolabelling, following the in vivo injection of 3H-17 beta estradiol, was increased only over the nuclei of tumor cells; stereologic analysis revealed a 4.5- to 6.7-times higher concentration of reduced silver grains over nuclei than cytoplasm of these cells. Despite rapid tubular excretion of estradiol which peaked in less than 1 h, the normal cells did not appear to bind the ligand. This is the first published report documenting the preferential in vivo binding of estrogen to nuclei of cells in estrogen induced hamster renal carcinomas.","[{'text': 'estrogen', 'type': 'Chemical', 'start': 29, 'end': 37, 'mesh': 'D004967'}, {'text': 'diethylstilbesterol', 'type': 'Chemical', 'start': 65, 'end': 84, 'mesh': 'D004054'}, {'text': 'renal carcinomas', 'type': 'Disease', 'start': 101, 'end': 117, 'mesh': 'D002292'}, {'text': 'Estrogen', 'type': 'Chemical', 'start': 119, 'end': 127, 'mesh': 'D004967'}, {'text': 'diethylstilbesterol', 'type': 'Chemical', 'start': 218, 'end': 237, 'mesh': 'D004054'}, {'text': 'renal carcinomas', 'type': 'Disease', 'start': 246, 'end': 262, 'mesh': 'D002292'}, {'text': 'estradiol', 'type': 'Chemical', 'start': 344, 'end': 353, 'mesh': 'D004958'}, {'text': 'tumor', 'type': 'Disease', 'start': 393, 'end': 398, 'mesh': 'D009369'}, {'text': 'silver', 'type': 'Chemical', 'start': 488, 'end': 494, 'mesh': 'D012834'}, {'text': 'estradiol', 'type': 'Chemical', 'start': 580, 'end': 589, 'mesh': 'D004958'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 756, 'end': 764, 'mesh': 'D004967'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 787, 'end': 795, 'mesh': 'D004967'}, {'text': 'renal carcinomas', 'type': 'Disease', 'start': 812, 'end': 828, 'mesh': 'D002292'}]"
+1183,2710809,Bradycardia due to biperiden.,"In a 38-year-old male patient suffering from a severe postzosteric trigeminal neuralgia, intravenous application of 10 mg biperiden lactate led to a long-lasting paradoxical reaction characterized by considerable bradycardia, dysarthria, and dysphagia. The heart rate was back to normal within 12 hours upon administration of orciprenaline under cardiac monitoring in an intensive care unit. Bradycardia induced by biperiden is attributed to the speed of injection and to a dose-related dual effect of atropine-like drugs on muscarine receptors.","[{'text': 'Bradycardia', 'type': 'Disease', 'start': 0, 'end': 11, 'mesh': 'D001919'}, {'text': 'biperiden', 'type': 'Chemical', 'start': 19, 'end': 28, 'mesh': 'D001712'}, {'text': 'postzosteric', 'type': 'Disease', 'start': 84, 'end': 96, 'mesh': 'D006562'}, {'text': 'trigeminal neuralgia', 'type': 'Disease', 'start': 97, 'end': 117, 'mesh': 'D014277'}, {'text': 'biperiden lactate', 'type': 'Chemical', 'start': 152, 'end': 169, 'mesh': 'C036432'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 243, 'end': 254, 'mesh': 'D001919'}, {'text': 'dysarthria', 'type': 'Disease', 'start': 256, 'end': 266, 'mesh': 'D004401'}, {'text': 'dysphagia', 'type': 'Disease', 'start': 272, 'end': 281, 'mesh': 'D003680'}, {'text': 'orciprenaline', 'type': 'Chemical', 'start': 356, 'end': 369, 'mesh': 'D009921'}, {'text': 'Bradycardia', 'type': 'Disease', 'start': 422, 'end': 433, 'mesh': 'D001919'}, {'text': 'biperiden', 'type': 'Chemical', 'start': 445, 'end': 454, 'mesh': 'D001712'}, {'text': 'atropine', 'type': 'Chemical', 'start': 532, 'end': 540, 'mesh': 'D001285'}, {'text': 'muscarine', 'type': 'Chemical', 'start': 555, 'end': 564, 'mesh': 'D009116'}]"
+1184,2718706,"Deliberate hypotension induced by labetalol with halothane, enflurane or isoflurane for middle-ear surgery.","The feasibility of using labetalol, an alpha- and beta-adrenergic blocking agent, as a hypotensive agent in combination with inhalation anaesthetics (halothane, enflurane or isoflurane) was studied in 23 adult patients undergoing middle-ear surgery. The mean arterial pressure was decreased from 86 +/- 5 (s.e. mean) mmHg to 52 +/- 1 mmHg (11.5 +/- 0.7 to 6.9 +/- 0.1 kPa) for 98 +/- 10 min in the halothane (H) group, from 79 +/- 5 to 53 +/- 1 mmHg (10.5 +/- 0.7 to 7.1 +/- 0.1 kPa) for 129 +/- 11 min in the enflurane (E) group, and from 80 +/- 4 to 49 +/- 1 mmHg (10.7 +/- 0.5 to 6.5 +/- 0.1 kPa) for 135 +/- 15 min in the isoflurane (I) group. The mean H concentration during hypotension in the inspiratory gas was 0.7 +/- 0.1 vol%, the mean E concentration 1.6 +/- 0.2 vol%, and the mean I concentration 1.0 +/- 0.1 vol%. In addition, the patients received fentanyl and d-tubocurarine. The initial dose of labetalol for lowering blood pressure was similar, 0.52-0.59 mg/kg, in all the groups. During hypotension, the heart rate was stable without tachy- or bradycardia. The operating conditions regarding bleeding were estimated in a double-blind manner, and did not differ significantly between the groups. During hypotension, the serum creatinine concentration rose significantly in all groups from the values before hypotension and returned postoperatively to the initial level in the other groups, except the isoflurane group. After hypotension there was no rebound phenomenon in either blood pressure or heart rate. These results indicate that labetalol induces easily adjustable hypotension without compensatory tachycardia and rebound hypertension.","[{'text': 'hypotension', 'type': 'Disease', 'start': 11, 'end': 22, 'mesh': 'D007022'}, {'text': 'labetalol', 'type': 'Chemical', 'start': 34, 'end': 43, 'mesh': 'D007741'}, {'text': 'halothane', 'type': 'Chemical', 'start': 49, 'end': 58, 'mesh': 'D006221'}, {'text': 'enflurane', 'type': 'Chemical', 'start': 60, 'end': 69, 'mesh': 'D004737'}, {'text': 'isoflurane', 'type': 'Chemical', 'start': 73, 'end': 83, 'mesh': 'D007530'}, {'text': 'labetalol', 'type': 'Chemical', 'start': 133, 'end': 142, 'mesh': 'D007741'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 195, 'end': 206, 'mesh': 'D007022'}, {'text': 'halothane', 'type': 'Chemical', 'start': 258, 'end': 267, 'mesh': 'D006221'}, {'text': 'enflurane', 'type': 'Chemical', 'start': 269, 'end': 278, 'mesh': 'D004737'}, {'text': 'isoflurane', 'type': 'Chemical', 'start': 282, 'end': 292, 'mesh': 'D007530'}, {'text': 'halothane', 'type': 'Chemical', 'start': 506, 'end': 515, 'mesh': 'D006221'}, {'text': 'H', 'type': 'Chemical', 'start': 517, 'end': 518, 'mesh': 'D006221'}, {'text': 'enflurane', 'type': 'Chemical', 'start': 618, 'end': 627, 'mesh': 'D004737'}, {'text': 'E', 'type': 'Chemical', 'start': 629, 'end': 630, 'mesh': 'D004737'}, {'text': 'isoflurane', 'type': 'Chemical', 'start': 734, 'end': 744, 'mesh': 'D007530'}, {'text': 'I', 'type': 'Chemical', 'start': 746, 'end': 747, 'mesh': 'D007530'}, {'text': 'H', 'type': 'Chemical', 'start': 765, 'end': 766, 'mesh': 'D006221'}, {'text': 'hypotension', 'type': 'Disease', 'start': 788, 'end': 799, 'mesh': 'D007022'}, {'text': 'E', 'type': 'Chemical', 'start': 854, 'end': 855, 'mesh': 'D004737'}, {'text': 'I', 'type': 'Chemical', 'start': 901, 'end': 902, 'mesh': 'D007530'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 970, 'end': 978, 'mesh': 'D005283'}, {'text': 'd-tubocurarine', 'type': 'Chemical', 'start': 983, 'end': 997, 'mesh': 'D014403'}, {'text': 'labetalol', 'type': 'Chemical', 'start': 1019, 'end': 1028, 'mesh': 'D007741'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1113, 'end': 1124, 'mesh': 'D007022'}, {'text': 'tachy- or bradycardia', 'type': 'Disease', 'start': 1160, 'end': 1181, 'mesh': 'D013610|D001919'}, {'text': 'bleeding', 'type': 'Disease', 'start': 1218, 'end': 1226, 'mesh': 'D006470'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1328, 'end': 1339, 'mesh': 'D007022'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1351, 'end': 1361, 'mesh': 'D003404'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1432, 'end': 1443, 'mesh': 'D007022'}, {'text': 'isoflurane', 'type': 'Chemical', 'start': 1526, 'end': 1536, 'mesh': 'D007530'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1550, 'end': 1561, 'mesh': 'D007022'}, {'text': 'labetalol', 'type': 'Chemical', 'start': 1662, 'end': 1671, 'mesh': 'D007741'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1698, 'end': 1709, 'mesh': 'D007022'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 1731, 'end': 1742, 'mesh': 'D013610'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1755, 'end': 1767, 'mesh': 'D006973'}]"
+1185,2765447,Convulsion following intravenous fluorescein angiography.,Tonic-clonic seizures followed intravenous fluorescein injection for fundus angiography in a 47-year-old male. Despite precautions this adverse reaction recurred on re-exposure to intravenous fluorescein.,"[{'text': 'Convulsion', 'type': 'Disease', 'start': 0, 'end': 10, 'mesh': 'D012640'}, {'text': 'fluorescein', 'type': 'Chemical', 'start': 33, 'end': 44, 'mesh': 'D019793'}, {'text': 'Tonic-clonic seizures', 'type': 'Disease', 'start': 58, 'end': 79, 'mesh': 'D004830'}, {'text': 'fluorescein', 'type': 'Chemical', 'start': 101, 'end': 112, 'mesh': 'D019793'}, {'text': 'fluorescein', 'type': 'Chemical', 'start': 250, 'end': 261, 'mesh': 'D019793'}]"
+1186,2767010,Pharmacology of ACC-9653 (phenytoin prodrug).,"ACC-9653, the disodium phosphate ester of 3-hydroxymethyl-5,5-diphenylhydantoin, is a prodrug of phenytoin with advantageous physicochemical properties. ACC-9653 is rapidly converted enzymatically to phenytoin in vivo. ACC-9653 and phenytoin sodium have equivalent anticonvulsant activity against seizures induced by maximal electroshock (MES) in mice following i.p., oral, or i.v. administration. The ED50 doses were 16 mg/kg for i.v. ACC-9653 and 8 mg/kg for i.v. phenytoin sodium. ACC-9653 and phenytoin sodium have similar antiarrhythmic activity against ouabain-induced ventricular tachycardia in anesthetized dogs. The total doses of ACC-9653 or phenytoin sodium necessary to convert the arrhythmia to a normal sinus rhythm were 24 +/- 6 and 14 +/- 3 mg/kg, respectively. Only phenytoin sodium displayed in vitro antiarrhythmic activity against strophanthidin-induced arrhythmias in guinea pig right atria. In anesthetized dogs, a high dose of ACC-9653 (31 mg/kg) was infused over 15, 20, and 30 min and the responses were compared to an equimolar dose of phenytoin sodium (21 mg/kg). The ACC-9653 and phenytoin sodium treatments produced similar marked reductions in diastolic blood pressure and contractile force (LVdP/dt). The maximum effects of each treatment occurred at the time of maximum phenytoin sodium levels. Acute toxicity studies of ACC-9653 and phenytoin sodium were carried out in mice, rats, rabbits, and dogs by i.v., i.m., and i.p. routes of administration. The systemic toxic signs of both agents were similar and occurred at approximately equivalent doses. Importantly, the local irritation of ACC-9653 was markedly less than phenytoin sodium following i.m. administration.(ABSTRACT TRUNCATED AT 250 WORDS)","[{'text': 'ACC-9653', 'type': 'Chemical', 'start': 16, 'end': 24, 'mesh': 'C043114'}, {'text': 'phenytoin', 'type': 'Chemical', 'start': 26, 'end': 35, 'mesh': 'D010672'}, {'text': 'ACC-9653', 'type': 'Chemical', 'start': 46, 'end': 54, 'mesh': 'C043114'}, {'text': 'disodium phosphate ester', 'type': 'Chemical', 'start': 60, 'end': 84, 'mesh': '-1'}, {'text': '3-hydroxymethyl-5,5-diphenylhydantoin', 'type': 'Chemical', 'start': 88, 'end': 125, 'mesh': 'C043104'}, {'text': 'phenytoin', 'type': 'Chemical', 'start': 143, 'end': 152, 'mesh': 'D010672'}, {'text': 'ACC-9653', 'type': 'Chemical', 'start': 199, 'end': 207, 'mesh': 'C043114'}, {'text': 'phenytoin', 'type': 'Chemical', 'start': 246, 'end': 255, 'mesh': 'D010672'}, {'text': 'ACC-9653', 'type': 'Chemical', 'start': 265, 'end': 273, 'mesh': 'C043114'}, {'text': 'phenytoin sodium', 'type': 'Chemical', 'start': 278, 'end': 294, 'mesh': 'C043114'}, {'text': 'seizures', 'type': 'Disease', 'start': 343, 'end': 351, 'mesh': 'D012640'}, {'text': 'ACC-9653', 'type': 'Chemical', 'start': 482, 'end': 490, 'mesh': 'C043114'}, {'text': 'phenytoin sodium', 'type': 'Chemical', 'start': 512, 'end': 528, 'mesh': 'C043114'}, {'text': 'ACC-9653', 'type': 'Chemical', 'start': 530, 'end': 538, 'mesh': 'C043114'}, {'text': 'phenytoin sodium', 'type': 'Chemical', 'start': 543, 'end': 559, 'mesh': 'C043114'}, {'text': 'ouabain', 'type': 'Chemical', 'start': 605, 'end': 612, 'mesh': 'D010042'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 621, 'end': 644, 'mesh': 'D017180'}, {'text': 'ACC-9653', 'type': 'Chemical', 'start': 686, 'end': 694, 'mesh': 'C043114'}, {'text': 'phenytoin sodium', 'type': 'Chemical', 'start': 698, 'end': 714, 'mesh': 'C043114'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 740, 'end': 750, 'mesh': 'D001145'}, {'text': 'phenytoin sodium', 'type': 'Chemical', 'start': 829, 'end': 845, 'mesh': 'C043114'}, {'text': 'strophanthidin', 'type': 'Chemical', 'start': 897, 'end': 911, 'mesh': 'D013327'}, {'text': 'arrhythmias', 'type': 'Disease', 'start': 920, 'end': 931, 'mesh': 'D001145'}, {'text': 'ACC-9653', 'type': 'Chemical', 'start': 996, 'end': 1004, 'mesh': 'C043114'}, {'text': 'phenytoin sodium', 'type': 'Chemical', 'start': 1108, 'end': 1124, 'mesh': 'C043114'}, {'text': 'ACC-9653', 'type': 'Chemical', 'start': 1141, 'end': 1149, 'mesh': 'C043114'}, {'text': 'phenytoin sodium', 'type': 'Chemical', 'start': 1154, 'end': 1170, 'mesh': 'C043114'}, {'text': 'phenytoin sodium', 'type': 'Chemical', 'start': 1348, 'end': 1364, 'mesh': 'C043114'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1379, 'end': 1387, 'mesh': 'D064420'}, {'text': 'ACC-9653', 'type': 'Chemical', 'start': 1399, 'end': 1407, 'mesh': 'C043114'}, {'text': 'phenytoin sodium', 'type': 'Chemical', 'start': 1412, 'end': 1428, 'mesh': 'C043114'}, {'text': 'ACC-9653', 'type': 'Chemical', 'start': 1667, 'end': 1675, 'mesh': 'C043114'}, {'text': 'phenytoin sodium', 'type': 'Chemical', 'start': 1699, 'end': 1715, 'mesh': 'C043114'}]"
+1187,2818777,Phenytoin induced fatal hepatic injury.,"A 61 year old female developed fatal hepatic failure after phenytoin administration. A typical multisystem clinical pattern precedes the manifestations of hepatic injury. The hematologic, biochemical and pathologic features indicate a mixed hepatocellular damage due to drug hypersensitivity. In a patient receiving phenytoin who presents a viral-like illness, early recognition and discontinuation of the drug are mandatory.","[{'text': 'Phenytoin', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D010672'}, {'text': 'hepatic injury', 'type': 'Disease', 'start': 24, 'end': 38, 'mesh': 'D056486'}, {'text': 'hepatic failure', 'type': 'Disease', 'start': 77, 'end': 92, 'mesh': 'D017093'}, {'text': 'phenytoin', 'type': 'Chemical', 'start': 99, 'end': 108, 'mesh': 'D010672'}, {'text': 'hepatic injury', 'type': 'Disease', 'start': 195, 'end': 209, 'mesh': 'D056486'}, {'text': 'hepatocellular damage', 'type': 'Disease', 'start': 281, 'end': 302, 'mesh': 'D056486'}, {'text': 'drug hypersensitivity', 'type': 'Disease', 'start': 310, 'end': 331, 'mesh': 'D004342'}, {'text': 'phenytoin', 'type': 'Chemical', 'start': 356, 'end': 365, 'mesh': 'D010672'}]"
+1188,2884595,Treatment of lethal pertussis vaccine reaction with histamine H1 antagonists.,"We studied mortality after pertussis immunization in the mouse. Without treatment, 73 of 92 animals (80%) died after injection of bovine serum albumin (BSA) on day +7 of pertussis immunization. After pretreatment with 3 mg of cyproheptadine, 2 mg mianserin, or 2 mg chlorpheniramine, only 5 of 105 animals (5%) died after receiving BSA on day +7 (p less than 0.001). Blockade of histamine H1 receptors may reduce mortality in pertussis immunization-induced encephalopathy in mice.","[{'text': 'pertussis vaccine', 'type': 'Chemical', 'start': 20, 'end': 37, 'mesh': 'D010567'}, {'text': 'histamine', 'type': 'Chemical', 'start': 52, 'end': 61, 'mesh': 'D006632'}, {'text': 'pertussis', 'type': 'Disease', 'start': 105, 'end': 114, 'mesh': 'D014917'}, {'text': 'pertussis', 'type': 'Disease', 'start': 248, 'end': 257, 'mesh': 'D014917'}, {'text': 'cyproheptadine', 'type': 'Chemical', 'start': 304, 'end': 318, 'mesh': 'D003533'}, {'text': 'mianserin', 'type': 'Chemical', 'start': 325, 'end': 334, 'mesh': 'D008803'}, {'text': 'chlorpheniramine', 'type': 'Chemical', 'start': 344, 'end': 360, 'mesh': 'D002744'}, {'text': 'histamine', 'type': 'Chemical', 'start': 457, 'end': 466, 'mesh': 'D006632'}, {'text': 'pertussis', 'type': 'Disease', 'start': 504, 'end': 513, 'mesh': 'D014917'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 535, 'end': 549, 'mesh': 'D001927'}]"
+1189,2904523,Support for adrenaline-hypertension hypothesis: 18 hour pressor effect after 6 hours adrenaline infusion.,"In a double blind, crossover study 6 h infusions of adrenaline (15 ng/kg/min; 1 ng = 5.458 pmol), noradrenaline (30 ng/kg/min; 1 ng = 5.911 pmol), and a 5% dextrose solution (5.4 ml/h), were given to ten healthy volunteers in random order 2 weeks apart. By means of intra-arterial ambulatory monitoring the haemodynamic effects were followed for 18 h after the infusions were stopped. Adrenaline, but not noradrenaline, caused a delayed and protracted pressor effect. Over the total postinfusion period systolic and diastolic arterial pressure were 6 (SEM 2)% and 7 (2)%, respectively, higher than after dextrose infusion (ANOVA, p less than 0.001). Thus, ""stress"" levels of adrenaline (230 pg/ml) for 6 h cause a delayed and protracted pressor effect. These findings are strong support for the adrenaline-hypertension hypothesis in man.","[{'text': 'adrenaline', 'type': 'Chemical', 'start': 12, 'end': 22, 'mesh': 'D004837'}, {'text': 'hypertension', 'type': 'Disease', 'start': 23, 'end': 35, 'mesh': 'D006973'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 85, 'end': 95, 'mesh': 'D004837'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 158, 'end': 168, 'mesh': 'D004837'}, {'text': 'noradrenaline', 'type': 'Chemical', 'start': 204, 'end': 217, 'mesh': 'D009638'}, {'text': 'dextrose', 'type': 'Chemical', 'start': 262, 'end': 270, 'mesh': 'D005947'}, {'text': 'Adrenaline', 'type': 'Chemical', 'start': 491, 'end': 501, 'mesh': 'D004837'}, {'text': 'noradrenaline', 'type': 'Chemical', 'start': 511, 'end': 524, 'mesh': 'D009638'}, {'text': 'dextrose', 'type': 'Chemical', 'start': 710, 'end': 718, 'mesh': 'D005947'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 781, 'end': 791, 'mesh': 'D004837'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 901, 'end': 911, 'mesh': 'D004837'}, {'text': 'hypertension', 'type': 'Disease', 'start': 912, 'end': 924, 'mesh': 'D006973'}]"
+1190,2907577,Effect of alkylxanthines on gentamicin-induced acute renal failure in the rat.,"Adenosine antagonists have been previously shown to be of benefit in some ischaemic and nephrotoxic models of acute renal failure (ARF). In the present study, the effects of three alkylxanthines with different potencies as adenosine antagonists 8-phenyltheophylline, theophylline and enprofylline, were examined in rats developing acute renal failure after 4 daily injections of gentamicin (200 mg kg-1). Renal function was assessed by biochemical (plasma urea and creatinine), functional (urine analysis and [3H]inulin and [14C]p-aminohippuric acid clearances) and morphological (degree of necrosis) indices. The various drug treatments produced improvements in some, but not all, measurements of renal function. However, any improvement produced by drug treatment was largely a result of a beneficial effect exerted by its vehicle (polyethylene glycol and NaOH). The lack of any consistent protective effect noted with the alkylxanthines tested in the present study indicates that adenosine plays little, if any, pathophysiological role in gentamicin-induced ARF.","[{'text': 'alkylxanthines', 'type': 'Chemical', 'start': 10, 'end': 24, 'mesh': '-1'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 28, 'end': 38, 'mesh': 'D005839'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 47, 'end': 66, 'mesh': 'D058186'}, {'text': 'Adenosine', 'type': 'Chemical', 'start': 79, 'end': 88, 'mesh': 'D000241'}, {'text': 'ischaemic', 'type': 'Disease', 'start': 153, 'end': 162, 'mesh': 'D007511'}, {'text': 'nephrotoxic', 'type': 'Disease', 'start': 167, 'end': 178, 'mesh': 'D007674'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 189, 'end': 208, 'mesh': 'D058186'}, {'text': 'ARF', 'type': 'Disease', 'start': 210, 'end': 213, 'mesh': 'D058186'}, {'text': 'alkylxanthines', 'type': 'Chemical', 'start': 259, 'end': 273, 'mesh': '-1'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 302, 'end': 311, 'mesh': 'D000241'}, {'text': '8-phenyltheophylline', 'type': 'Chemical', 'start': 324, 'end': 344, 'mesh': 'C028322'}, {'text': 'theophylline', 'type': 'Chemical', 'start': 346, 'end': 358, 'mesh': 'D013806'}, {'text': 'enprofylline', 'type': 'Chemical', 'start': 363, 'end': 375, 'mesh': 'C034347'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 410, 'end': 429, 'mesh': 'D058186'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 458, 'end': 468, 'mesh': 'D005839'}, {'text': 'urea', 'type': 'Chemical', 'start': 535, 'end': 539, 'mesh': 'D014508'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 544, 'end': 554, 'mesh': 'D003404'}, {'text': 'p-aminohippuric acid', 'type': 'Chemical', 'start': 608, 'end': 628, 'mesh': 'D010130'}, {'text': 'necrosis', 'type': 'Disease', 'start': 670, 'end': 678, 'mesh': 'D009336'}, {'text': 'polyethylene glycol', 'type': 'Chemical', 'start': 913, 'end': 932, 'mesh': 'D011092'}, {'text': 'NaOH', 'type': 'Chemical', 'start': 937, 'end': 941, 'mesh': 'D012972'}, {'text': 'alkylxanthines', 'type': 'Chemical', 'start': 1004, 'end': 1018, 'mesh': '-1'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 1062, 'end': 1071, 'mesh': 'D000241'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 1121, 'end': 1131, 'mesh': 'D005839'}, {'text': 'ARF', 'type': 'Disease', 'start': 1140, 'end': 1143, 'mesh': 'D058186'}]"
+1191,2931989,Adverse ocular reactions possibly associated with isotretinoin.,"A total of 261 adverse ocular reactions occurred in 237 patients who received isotretinoin, a commonly used drug in the treatment of severe cystic acne. Blepharoconjunctivitis, subjective complaints of dry eyes, blurred vision, contact lens intolerance, and photodermatitis are reversible side effects. More serious ocular adverse reactions include papilledema, pseudotumor cerebri, and white or gray subepithelial corneal opacities; all of these are reversible if the drug is discontinued. Reported cases of decreased dark adaptation are under investigation. Isotretinoin is contraindicated in pregnancy because of the many reported congenital abnormalities after maternal use (including microphthalmos, orbital hypertelorism, and optic nerve hypoplasia).","[{'text': 'isotretinoin', 'type': 'Chemical', 'start': 50, 'end': 62, 'mesh': 'D015474'}, {'text': 'isotretinoin', 'type': 'Chemical', 'start': 142, 'end': 154, 'mesh': 'D015474'}, {'text': 'acne', 'type': 'Disease', 'start': 211, 'end': 215, 'mesh': 'D000152'}, {'text': 'Blepharoconjunctivitis', 'type': 'Disease', 'start': 217, 'end': 239, 'mesh': 'D003231'}, {'text': 'dry eyes', 'type': 'Disease', 'start': 266, 'end': 274, 'mesh': 'D014985'}, {'text': 'blurred vision', 'type': 'Disease', 'start': 276, 'end': 290, 'mesh': 'D014786'}, {'text': 'photodermatitis', 'type': 'Disease', 'start': 322, 'end': 337, 'mesh': 'D010787'}, {'text': 'papilledema', 'type': 'Disease', 'start': 413, 'end': 424, 'mesh': 'D010211'}, {'text': 'pseudotumor cerebri', 'type': 'Disease', 'start': 426, 'end': 445, 'mesh': 'D011559'}, {'text': 'corneal opacities', 'type': 'Disease', 'start': 479, 'end': 496, 'mesh': 'D003318'}, {'text': 'Isotretinoin', 'type': 'Chemical', 'start': 624, 'end': 636, 'mesh': 'D015474'}, {'text': 'congenital abnormalities', 'type': 'Disease', 'start': 698, 'end': 722, 'mesh': 'D000013'}, {'text': 'microphthalmos', 'type': 'Disease', 'start': 753, 'end': 767, 'mesh': 'D008850'}, {'text': 'hypertelorism', 'type': 'Disease', 'start': 777, 'end': 790, 'mesh': 'D006972'}, {'text': 'optic nerve hypoplasia', 'type': 'Disease', 'start': 796, 'end': 818, 'mesh': 'C563492'}]"
+1192,2933998,"Procaterol and terbutaline in bronchial asthma. A double-blind, placebo-controlled, cross-over study.","Procaterol, a new beta-2 adrenoceptor stimulant, was studied in a double-blind, placebo-controlled, cross-over trial in patients with bronchial asthma. Oral procaterol 50 micrograms b.d., procaterol 100 micrograms b.d., and terbutaline 5 mg t.i.d., were compared when given randomly in 1-week treatment periods. The best clinical effect was found with terbutaline. Both anti-asthmatic and tremorgenic effects of procaterol were dose-related. Procaterol appeared effective in the doses tested, and a twice daily regimen would appear to be suitable with this drug.","[{'text': 'Procaterol', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D017265'}, {'text': 'terbutaline', 'type': 'Chemical', 'start': 15, 'end': 26, 'mesh': 'D013726'}, {'text': 'bronchial asthma', 'type': 'Disease', 'start': 30, 'end': 46, 'mesh': 'D001249'}, {'text': 'Procaterol', 'type': 'Chemical', 'start': 102, 'end': 112, 'mesh': 'D017265'}, {'text': 'bronchial asthma', 'type': 'Disease', 'start': 236, 'end': 252, 'mesh': 'D001249'}, {'text': 'procaterol', 'type': 'Chemical', 'start': 259, 'end': 269, 'mesh': 'D017265'}, {'text': 'procaterol', 'type': 'Chemical', 'start': 290, 'end': 300, 'mesh': 'D017265'}, {'text': 'terbutaline', 'type': 'Chemical', 'start': 326, 'end': 337, 'mesh': 'D013726'}, {'text': 'terbutaline', 'type': 'Chemical', 'start': 454, 'end': 465, 'mesh': 'D013726'}, {'text': 'asthmatic', 'type': 'Disease', 'start': 477, 'end': 486, 'mesh': 'D001249'}, {'text': 'tremorgenic', 'type': 'Disease', 'start': 491, 'end': 502, 'mesh': 'D014202'}, {'text': 'procaterol', 'type': 'Chemical', 'start': 514, 'end': 524, 'mesh': 'D017265'}, {'text': 'Procaterol', 'type': 'Chemical', 'start': 544, 'end': 554, 'mesh': 'D017265'}]"
+1193,2974281,Subacute effects of propranolol and B 24/76 on isoproterenol-induced rat heart hypertrophy in correlation with blood pressure.,"We compared the potential beta-receptor blocker, B 24/76 i.e. 1-(2,4-dichlorophenoxy)-3[2-3,4-dimethoxyphenyl)ethanolamino]-prop an-2-ol, which is characterized by beta 1-adrenoceptor blocking and beta 2-adrenoceptor stimulating properties with propranolol. The studies were performed using an experimental model of isoproterenol-induced heart hypertrophy in rats. A correlation of the blood pressure was neither found in the development nor in the attempt to suppress the development of heart hypertrophy with the two beta-receptor blockers. Both beta-blockers influenced the development of hypertrophy to a different, but not reproducible extent. It was possible to suppress the increased ornithine decarboxylase activity with both beta-blockers in hypertrophied hearts, but there was no effect on the heart mass. Neither propranolol nor B 24/76 could stop the changes in the characteristic myosin isoenzyme pattern of the hypertrophied rat heart. Thus, the investigations did not provide any evidence that the beta-receptor blockers propranolol and B 24/76 have the potency to prevent isoproterenol from producing heart hypertrophy.","[{'text': 'propranolol', 'type': 'Chemical', 'start': 20, 'end': 31, 'mesh': 'D011433'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 47, 'end': 60, 'mesh': 'D007545'}, {'text': 'heart hypertrophy', 'type': 'Disease', 'start': 73, 'end': 90, 'mesh': 'D006332'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 372, 'end': 383, 'mesh': 'D011433'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 443, 'end': 456, 'mesh': 'D007545'}, {'text': 'heart hypertrophy', 'type': 'Disease', 'start': 465, 'end': 482, 'mesh': 'D006332'}, {'text': 'heart hypertrophy', 'type': 'Disease', 'start': 615, 'end': 632, 'mesh': 'D006332'}, {'text': 'hypertrophy', 'type': 'Disease', 'start': 719, 'end': 730, 'mesh': 'D006984'}, {'text': 'ornithine', 'type': 'Chemical', 'start': 818, 'end': 827, 'mesh': 'D009952'}, {'text': 'hypertrophied hearts', 'type': 'Disease', 'start': 878, 'end': 898, 'mesh': 'D006332'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 951, 'end': 962, 'mesh': 'D011433'}, {'text': 'hypertrophied', 'type': 'Disease', 'start': 1052, 'end': 1065, 'mesh': 'D006984'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 1163, 'end': 1174, 'mesh': 'D011433'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1215, 'end': 1228, 'mesh': 'D007545'}, {'text': 'heart hypertrophy', 'type': 'Disease', 'start': 1244, 'end': 1261, 'mesh': 'D006332'}]"
+1194,3074291,Comparison of the effect of oxitropium bromide and of slow-release theophylline on nocturnal asthma.,"The effects of a new inhaled antimuscarinic drug, oxitropium bromide, and of a slow-release theophylline preparation upon nocturnal asthma were compared in a placebo-controlled double-blind study. Two samples were studied: 12 patients received oxitropium at 600 micrograms (6 subjects) or at 400 micrograms t.i.d. (6 subjects) whereas 11 received theophylline at 300 mg b.i.d. Morning dipping, assessed by the fall in peak flow overnight, was significantly reduced in the periods when either active drug was taken, whereas no difference was noticed during the placebo administration. No significant difference was noticed between results obtained with either active drug, as well as with either dosage of oxitropium. No subject reported side effects of oxitropium, as compared to three subjects reporting nausea, vomiting and tremors after theophylline. Oxitropium proves to be a valuable alternative to theophylline in nocturnal asthma, since it is equally potent, safer and does not require the titration of dosage.","[{'text': 'oxitropium bromide', 'type': 'Chemical', 'start': 28, 'end': 46, 'mesh': 'C017590'}, {'text': 'theophylline', 'type': 'Chemical', 'start': 67, 'end': 79, 'mesh': 'D013806'}, {'text': 'asthma', 'type': 'Disease', 'start': 93, 'end': 99, 'mesh': 'D001249'}, {'text': 'oxitropium bromide', 'type': 'Chemical', 'start': 151, 'end': 169, 'mesh': 'C017590'}, {'text': 'theophylline', 'type': 'Chemical', 'start': 193, 'end': 205, 'mesh': 'D013806'}, {'text': 'asthma', 'type': 'Disease', 'start': 233, 'end': 239, 'mesh': 'D001249'}, {'text': 'oxitropium', 'type': 'Chemical', 'start': 345, 'end': 355, 'mesh': 'C017590'}, {'text': 'theophylline', 'type': 'Chemical', 'start': 448, 'end': 460, 'mesh': 'D013806'}, {'text': 'oxitropium', 'type': 'Chemical', 'start': 806, 'end': 816, 'mesh': 'C017590'}, {'text': 'oxitropium', 'type': 'Chemical', 'start': 854, 'end': 864, 'mesh': 'C017590'}, {'text': 'nausea', 'type': 'Disease', 'start': 906, 'end': 912, 'mesh': 'D009325'}, {'text': 'vomiting', 'type': 'Disease', 'start': 914, 'end': 922, 'mesh': 'D014839'}, {'text': 'tremors', 'type': 'Disease', 'start': 927, 'end': 934, 'mesh': 'D014202'}, {'text': 'theophylline', 'type': 'Chemical', 'start': 941, 'end': 953, 'mesh': 'D013806'}, {'text': 'Oxitropium', 'type': 'Chemical', 'start': 955, 'end': 965, 'mesh': 'C017590'}, {'text': 'theophylline', 'type': 'Chemical', 'start': 1005, 'end': 1017, 'mesh': 'D013806'}, {'text': 'asthma', 'type': 'Disease', 'start': 1031, 'end': 1037, 'mesh': 'D001249'}]"
+1195,3083835,Penicillin anaphylaxis.,"A case of oral penicillin anaphylaxis is described, and the terminology, occurrence, clinical manifestations, pathogenesis, prevention, and treatment of anaphylaxis are reviewed. Emergency physicians should be aware of oral penicillin anaphylaxis in order to prevent its occurrence by prescribing the antibiotic judiciously and knowledgeably and to offer optimal medical therapy once this life-threatening reaction has begun.","[{'text': 'Penicillin', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D010406'}, {'text': 'anaphylaxis', 'type': 'Disease', 'start': 11, 'end': 22, 'mesh': 'D000707'}, {'text': 'penicillin', 'type': 'Chemical', 'start': 39, 'end': 49, 'mesh': 'D010406'}, {'text': 'anaphylaxis', 'type': 'Disease', 'start': 50, 'end': 61, 'mesh': 'D000707'}, {'text': 'anaphylaxis', 'type': 'Disease', 'start': 177, 'end': 188, 'mesh': 'D000707'}, {'text': 'penicillin', 'type': 'Chemical', 'start': 248, 'end': 258, 'mesh': 'D010406'}, {'text': 'anaphylaxis', 'type': 'Disease', 'start': 259, 'end': 270, 'mesh': 'D000707'}]"
+1196,3084231,Reversible valproic acid-induced dementia: a case report.,"Reversible valproic acid-induced dementia was documented in a 21-year-old man with epilepsy who had a 3-year history of insidious progressive decline in global cognitive abilities documented by serial neuropsychological studies. Repeat neuropsychological testing 7 weeks after discontinuation of the drug revealed dramatic improvement in IQ, memory, naming, and other tasks commensurate with clinical recovery in his intellectual capacity. Possible pathophysiological mechanisms which may have been operative in this case include: a direct central nervous system (CNS) toxic effect of valproic acid; a paradoxical epileptogenic effect secondary to the drug; and an indirect CNS toxic effect mediated through valproic acid-induced hyperammonemia.","[{'text': 'valproic acid', 'type': 'Chemical', 'start': 11, 'end': 24, 'mesh': 'D014635'}, {'text': 'dementia', 'type': 'Disease', 'start': 33, 'end': 41, 'mesh': 'D003704'}, {'text': 'valproic acid', 'type': 'Chemical', 'start': 69, 'end': 82, 'mesh': 'D014635'}, {'text': 'dementia', 'type': 'Disease', 'start': 91, 'end': 99, 'mesh': 'D003704'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 141, 'end': 149, 'mesh': 'D004827'}, {'text': 'valproic acid', 'type': 'Chemical', 'start': 643, 'end': 656, 'mesh': 'D014635'}, {'text': 'valproic acid', 'type': 'Chemical', 'start': 766, 'end': 779, 'mesh': 'D014635'}, {'text': 'hyperammonemia', 'type': 'Disease', 'start': 788, 'end': 802, 'mesh': 'D022124'}]"
+1197,3088653,Reversal of scopolamine-induced amnesia of passive avoidance by pre- and post-training naloxone.,"In a series of five experiments, the modulating role of naloxone on a scopolamine-induced retention deficit in a passive avoidance paradigm was investigated in mice. Scopolamine, but not methyl scopolamine (1 and 3 mg/kg), induced an amnesia as measured by latency and duration parameters. Naloxone (0.3, 1, 3, and 10 mg/kg) injected prior to training attenuated the retention deficit with a peak of activity at 3 mg/kg. The effect of naloxone could be antagonized with morphine (1, 3, and 10 mg/kg), demonstrating the opioid specificity of the naloxone effect. Post-training administration of naloxone (3 mg/kg) as a single or as a split dose also attenuated the scopolamine-induced amnesia. Control experiments indicated that neither an increase in pain sensitivity (pre-training naloxone) nor an induced aversive state (post-training naloxone) appear to be responsible for the influence of naloxone on the scopolamine-induced retention deficit. These results extend previous findings implicating a cholinergic-opioid interaction in memory processes. A possible mechanism for this interaction involving the septo-hippocampal cholinergic pathway is discussed.","[{'text': 'scopolamine', 'type': 'Chemical', 'start': 12, 'end': 23, 'mesh': 'D012601'}, {'text': 'amnesia', 'type': 'Disease', 'start': 32, 'end': 39, 'mesh': 'D000647'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 87, 'end': 95, 'mesh': 'D009270'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 153, 'end': 161, 'mesh': 'D009270'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 167, 'end': 178, 'mesh': 'D012601'}, {'text': 'retention deficit', 'type': 'Disease', 'start': 187, 'end': 204, 'mesh': 'D008569'}, {'text': 'Scopolamine', 'type': 'Chemical', 'start': 263, 'end': 274, 'mesh': 'D012601'}, {'text': 'methyl scopolamine', 'type': 'Chemical', 'start': 284, 'end': 302, 'mesh': 'D019832'}, {'text': 'amnesia', 'type': 'Disease', 'start': 331, 'end': 338, 'mesh': 'D000647'}, {'text': 'Naloxone', 'type': 'Chemical', 'start': 387, 'end': 395, 'mesh': 'D009270'}, {'text': 'retention deficit', 'type': 'Disease', 'start': 464, 'end': 481, 'mesh': 'D008569'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 532, 'end': 540, 'mesh': 'D009270'}, {'text': 'morphine', 'type': 'Chemical', 'start': 567, 'end': 575, 'mesh': 'D009020'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 642, 'end': 650, 'mesh': 'D009270'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 691, 'end': 699, 'mesh': 'D009270'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 761, 'end': 772, 'mesh': 'D012601'}, {'text': 'amnesia', 'type': 'Disease', 'start': 781, 'end': 788, 'mesh': 'D000647'}, {'text': 'pain', 'type': 'Disease', 'start': 848, 'end': 852, 'mesh': 'D010146'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 879, 'end': 887, 'mesh': 'D009270'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 934, 'end': 942, 'mesh': 'D009270'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 990, 'end': 998, 'mesh': 'D009270'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 1006, 'end': 1017, 'mesh': 'D012601'}, {'text': 'retention deficit', 'type': 'Disease', 'start': 1026, 'end': 1043, 'mesh': 'D008569'}]"
+1198,3109094,Electron microscopic investigations of the cyclophosphamide-induced lesions of the urinary bladder of the rat and their prevention by mesna.,"Fully developed cyclophosphamide-induced cystitis is characterized by nearly complete detachment of the urothelium, severe submucosal edema owing to damage to the microvascular bed and focal muscle necroses. The initial response to the primary attack by the cyclophosphamide metabolites seems to be fragmentation of the luminal membrane. This damages the cellular barrier against the hypertonic urine. Subsequent breaks in the lateral cell membranes of the superficial cells and in all the plasma membranes of the intermediate and basal cells, intercellular and intracellular edema and disintegration of the desmosomes and hemidesmosomes lead to progressive degeneration and detachment of the epithelial cells with exposure and splitting of the basal membrane. The morphological changes of the endothelial cells, which become more pronounced in the later stages of the experiment, the involvement of blood vessels regardless of their diameter and the location-dependent extent of the damage indicate a direct type of damage which is preceded by a mediator-induced increase in permeability, the morphological correlate of which is the formation of gaps in the interendothelial cell connections on the venules. These changes can be effectively prevented by mesna. The only sign of a possible involvement is the increase in the number of specific granules with a presumed lysosomal function in the superficial cells.","[{'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 43, 'end': 59, 'mesh': 'D003520'}, {'text': 'lesions of the urinary bladder', 'type': 'Disease', 'start': 68, 'end': 98, 'mesh': 'D001745'}, {'text': 'mesna', 'type': 'Chemical', 'start': 134, 'end': 139, 'mesh': 'D015080'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 157, 'end': 173, 'mesh': 'D003520'}, {'text': 'cystitis', 'type': 'Disease', 'start': 182, 'end': 190, 'mesh': 'D003556'}, {'text': 'edema', 'type': 'Disease', 'start': 275, 'end': 280, 'mesh': 'D004487'}, {'text': 'necroses', 'type': 'Disease', 'start': 339, 'end': 347, 'mesh': 'D009336'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 399, 'end': 415, 'mesh': 'D003520'}, {'text': 'luminal', 'type': 'Chemical', 'start': 461, 'end': 468, 'mesh': 'D010634'}, {'text': 'edema', 'type': 'Disease', 'start': 717, 'end': 722, 'mesh': 'D004487'}, {'text': 'mesna', 'type': 'Chemical', 'start': 1396, 'end': 1401, 'mesh': 'D015080'}]"
+1199,3125850,Increase in intragastric pressure during suxamethonium-induced muscle fasciculations in children: inhibition by alfentanil.,"Changes in intragastric pressure after the administration of suxamethonium 1.5 mg kg-1 i.v. were studied in 32 children (mean age 6.9 yr) pretreated with either physiological saline or alfentanil 50 micrograms kg-1. Anaesthesia was induced with thiopentone 5 mg kg-1. The incidence and intensity of muscle fasciculations caused by suxamethonium were significantly greater in the control than in the alfentanil group. The intragastric pressure during muscle fasciculations was significantly higher in the control group (16 +/- 0.7 (SEM) cm H2O) than in the alfentanil group (7.7 +/- 1.5 (SEM) cm H2O). The increase in intragastric pressure was directly related to the intensity of muscle fasciculations (regression line: y = 0.5 + 4.78x with r of 0.78). It is concluded that intragastric pressure increases significantly during muscle fasciculations caused by suxamethonium in healthy children. Alfentanil 50 micrograms kg-1 effectively inhibits the incidence and intensity of suxamethonium-induced muscle fasciculations; moreover, intragastric pressure remains at its control value.","[{'text': 'suxamethonium', 'type': 'Chemical', 'start': 41, 'end': 54, 'mesh': 'D013390'}, {'text': 'muscle fasciculations', 'type': 'Disease', 'start': 63, 'end': 84, 'mesh': 'D005207'}, {'text': 'alfentanil', 'type': 'Chemical', 'start': 112, 'end': 122, 'mesh': 'D015760'}, {'text': 'suxamethonium', 'type': 'Chemical', 'start': 185, 'end': 198, 'mesh': 'D013390'}, {'text': 'alfentanil', 'type': 'Chemical', 'start': 309, 'end': 319, 'mesh': 'D015760'}, {'text': 'thiopentone', 'type': 'Chemical', 'start': 369, 'end': 380, 'mesh': 'D013874'}, {'text': 'muscle fasciculations', 'type': 'Disease', 'start': 423, 'end': 444, 'mesh': 'D005207'}, {'text': 'suxamethonium', 'type': 'Chemical', 'start': 455, 'end': 468, 'mesh': 'D013390'}, {'text': 'alfentanil', 'type': 'Chemical', 'start': 523, 'end': 533, 'mesh': 'D015760'}, {'text': 'muscle fasciculations', 'type': 'Disease', 'start': 574, 'end': 595, 'mesh': 'D005207'}, {'text': 'H2O', 'type': 'Chemical', 'start': 663, 'end': 666, 'mesh': 'D014867'}, {'text': 'alfentanil', 'type': 'Chemical', 'start': 680, 'end': 690, 'mesh': 'D015760'}, {'text': 'H2O', 'type': 'Chemical', 'start': 719, 'end': 722, 'mesh': 'D014867'}, {'text': 'muscle fasciculations', 'type': 'Disease', 'start': 804, 'end': 825, 'mesh': 'D005207'}, {'text': 'muscle fasciculations', 'type': 'Disease', 'start': 951, 'end': 972, 'mesh': 'D005207'}, {'text': 'suxamethonium', 'type': 'Chemical', 'start': 983, 'end': 996, 'mesh': 'D013390'}, {'text': 'Alfentanil', 'type': 'Chemical', 'start': 1018, 'end': 1028, 'mesh': 'D015760'}, {'text': 'suxamethonium', 'type': 'Chemical', 'start': 1100, 'end': 1113, 'mesh': 'D013390'}, {'text': 'muscle fasciculations', 'type': 'Disease', 'start': 1122, 'end': 1143, 'mesh': 'D005207'}]"
+1200,3155884,Acute insulin treatment normalizes the resistance to the cardiotoxic effect of isoproterenol in streptozotocin diabetic rats. A morphometric study of isoproterenol induced myocardial fibrosis.,"The acute effect of insulin treatment on the earlier reported protective effect of streptozotocin diabetes against the cardiotoxic effect of high doses of isoproterenol (ISO) was investigated in rats. Thirty to 135 min after the injection of crystalline insulin, ISO was given subcutaneously and when ISO induced fibrosis in the myocardium was morphometrically analyzed 7 days later, a highly significant correlation (r = 0.83, 2 p = 0.006) to the slope of the fall in blood glucose after insulin treatment appeared. The myocardial content of catecholamines was estimated in these 8 day diabetic rats. The norepinephrine content was significantly increased while epinephrine remained unchanged. An enhanced sympathetic nervous system activity with a consequent down regulation of the myocardial beta-adrenergic receptors could, therefore, explain this catecholamine resistance. The rapid reversion after insulin treatment excludes the possibility that streptozotocin in itself causes the ISO resistance and points towards a direct insulin effect on myocardial catecholamine sensitivity in diabetic rats. The phenomenon described might elucidate pathogenetic mechanisms behind toxic myocardial cell degeneration and may possibly have relevance for acute cardiovascular complications in diabetic patients.","[{'text': 'cardiotoxic', 'type': 'Disease', 'start': 57, 'end': 68, 'mesh': 'D066126'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 79, 'end': 92, 'mesh': 'D007545'}, {'text': 'streptozotocin', 'type': 'Chemical', 'start': 96, 'end': 110, 'mesh': 'D013311'}, {'text': 'diabetic', 'type': 'Disease', 'start': 111, 'end': 119, 'mesh': 'D003920'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 150, 'end': 163, 'mesh': 'D007545'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 183, 'end': 191, 'mesh': 'D005355'}, {'text': 'streptozotocin', 'type': 'Chemical', 'start': 276, 'end': 290, 'mesh': 'D013311'}, {'text': 'diabetes', 'type': 'Disease', 'start': 291, 'end': 299, 'mesh': 'D003920'}, {'text': 'cardiotoxic', 'type': 'Disease', 'start': 312, 'end': 323, 'mesh': 'D066126'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 348, 'end': 361, 'mesh': 'D007545'}, {'text': 'ISO', 'type': 'Chemical', 'start': 363, 'end': 366, 'mesh': 'D007545'}, {'text': 'ISO', 'type': 'Chemical', 'start': 456, 'end': 459, 'mesh': 'D007545'}, {'text': 'ISO', 'type': 'Chemical', 'start': 494, 'end': 497, 'mesh': 'D007545'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 506, 'end': 514, 'mesh': 'D005355'}, {'text': 'glucose', 'type': 'Chemical', 'start': 668, 'end': 675, 'mesh': 'D005947'}, {'text': 'catecholamines', 'type': 'Chemical', 'start': 736, 'end': 750, 'mesh': 'D002395'}, {'text': 'diabetic', 'type': 'Disease', 'start': 780, 'end': 788, 'mesh': 'D003920'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 799, 'end': 813, 'mesh': 'D009638'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 856, 'end': 867, 'mesh': 'D004837'}, {'text': 'catecholamine', 'type': 'Chemical', 'start': 1045, 'end': 1058, 'mesh': 'D002395'}, {'text': 'streptozotocin', 'type': 'Chemical', 'start': 1145, 'end': 1159, 'mesh': 'D013311'}, {'text': 'ISO', 'type': 'Chemical', 'start': 1181, 'end': 1184, 'mesh': 'D007545'}, {'text': 'catecholamine', 'type': 'Chemical', 'start': 1253, 'end': 1266, 'mesh': 'D002395'}, {'text': 'diabetic', 'type': 'Disease', 'start': 1282, 'end': 1290, 'mesh': 'D003920'}, {'text': 'diabetic', 'type': 'Disease', 'start': 1478, 'end': 1486, 'mesh': 'D003920'}]"
+1201,3191389,Differential effects of non-steroidal anti-inflammatory drugs on seizures produced by pilocarpine in rats.,"The muscarinic cholinergic agonist pilocarpine induces in rats seizures and status epilepticus followed by widespread damage to the forebrain. The present study was designed to investigate the effect of 5 non-steroidal anti-inflammatory drugs, sodium salicylate, phenylbutazone, indomethacin, ibuprofen and mefenamic acid, on seizures produced by pilocarpine. Pretreatment of rats with sodium salicylate, ED50 103 mg/kg (60-174), and phenylbutazone, 59 mg/kg (50-70) converted the non-convulsant dose of pilocarpine, 200 mg/kg, to a convulsant one. Indomethacin, 1-10 mg/kg, and ibuprofen, 10-100 mg/kg, failed to modulate seizures produced by pilocarpine. Mefenamic acid, 26 (22-30) mg/kg, prevented seizures and protected rats from seizure-related brain damage induced by pilocarpine, 380 mg/kg. These results indicate that non-steroidal anti-inflammatory drugs differentially modulate the threshold for pilocarpine-induced seizures.","[{'text': 'seizures', 'type': 'Disease', 'start': 65, 'end': 73, 'mesh': 'D012640'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 86, 'end': 97, 'mesh': 'D010862'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 142, 'end': 153, 'mesh': 'D010862'}, {'text': 'seizures', 'type': 'Disease', 'start': 170, 'end': 178, 'mesh': 'D012640'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 183, 'end': 201, 'mesh': 'D013226'}, {'text': 'sodium salicylate', 'type': 'Chemical', 'start': 351, 'end': 368, 'mesh': 'D012980'}, {'text': 'phenylbutazone', 'type': 'Chemical', 'start': 370, 'end': 384, 'mesh': 'D010653'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 386, 'end': 398, 'mesh': 'D007213'}, {'text': 'ibuprofen', 'type': 'Chemical', 'start': 400, 'end': 409, 'mesh': 'D007052'}, {'text': 'mefenamic acid', 'type': 'Chemical', 'start': 414, 'end': 428, 'mesh': 'D008528'}, {'text': 'seizures', 'type': 'Disease', 'start': 433, 'end': 441, 'mesh': 'D012640'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 454, 'end': 465, 'mesh': 'D010862'}, {'text': 'sodium salicylate', 'type': 'Chemical', 'start': 493, 'end': 510, 'mesh': 'D012980'}, {'text': 'phenylbutazone', 'type': 'Chemical', 'start': 541, 'end': 555, 'mesh': 'D010653'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 611, 'end': 622, 'mesh': 'D010862'}, {'text': 'Indomethacin', 'type': 'Chemical', 'start': 656, 'end': 668, 'mesh': 'D007213'}, {'text': 'ibuprofen', 'type': 'Chemical', 'start': 686, 'end': 695, 'mesh': 'D007052'}, {'text': 'seizures', 'type': 'Disease', 'start': 730, 'end': 738, 'mesh': 'D012640'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 751, 'end': 762, 'mesh': 'D010862'}, {'text': 'Mefenamic acid', 'type': 'Chemical', 'start': 764, 'end': 778, 'mesh': 'D008528'}, {'text': 'seizures', 'type': 'Disease', 'start': 808, 'end': 816, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 841, 'end': 848, 'mesh': 'D012640'}, {'text': 'brain damage', 'type': 'Disease', 'start': 857, 'end': 869, 'mesh': 'D001930'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 881, 'end': 892, 'mesh': 'D010862'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1013, 'end': 1024, 'mesh': 'D010862'}, {'text': 'seizures', 'type': 'Disease', 'start': 1033, 'end': 1041, 'mesh': 'D012640'}]"
+1202,3289726,Acute neurologic dysfunction after high-dose etoposide therapy for malignant glioma.,"Etoposide (VP-16-213) has been used in the treatment of many solid tumors and hematologic malignancies. When used in high doses and in conjunction with autologous bone marrow transplantation, this agent has activity against several treatment-resistant cancers including malignant glioma. In six of eight patients (75%) who we treated for recurrent or resistant glioma, sudden severe neurologic deterioration occurred. This developed a median of 9 days after initiation of high-dose etoposide therapy. Significant clinical manifestations have included confusion, papilledema, somnolence, exacerbation of motor deficits, and sharp increase in seizure activity. These abnormalities resolved rapidly after initiation of high-dose intravenous dexamethasone therapy. In all patients, computerized tomographic (CT) brain scans demonstrated stability in tumor size and peritumor edema when compared with pretransplant scans. This complication appears to represent a significant new toxicity of high-dose etoposide therapy for malignant glioma.","[{'text': 'Acute neurologic dysfunction', 'type': 'Disease', 'start': 0, 'end': 28, 'mesh': 'D009422'}, {'text': 'etoposide', 'type': 'Chemical', 'start': 45, 'end': 54, 'mesh': 'D005047'}, {'text': 'malignant glioma', 'type': 'Disease', 'start': 67, 'end': 83, 'mesh': 'D005910'}, {'text': 'Etoposide', 'type': 'Chemical', 'start': 85, 'end': 94, 'mesh': 'D005047'}, {'text': 'VP-16-213', 'type': 'Chemical', 'start': 96, 'end': 105, 'mesh': 'D005047'}, {'text': 'tumors', 'type': 'Disease', 'start': 152, 'end': 158, 'mesh': 'D009369'}, {'text': 'hematologic malignancies', 'type': 'Disease', 'start': 163, 'end': 187, 'mesh': 'D019337'}, {'text': 'cancers', 'type': 'Disease', 'start': 337, 'end': 344, 'mesh': 'D009369'}, {'text': 'malignant glioma', 'type': 'Disease', 'start': 355, 'end': 371, 'mesh': 'D005910'}, {'text': 'glioma', 'type': 'Disease', 'start': 446, 'end': 452, 'mesh': 'D005910'}, {'text': 'neurologic deterioration', 'type': 'Disease', 'start': 468, 'end': 492, 'mesh': 'D009422'}, {'text': 'etoposide', 'type': 'Chemical', 'start': 567, 'end': 576, 'mesh': 'D005047'}, {'text': 'confusion', 'type': 'Disease', 'start': 636, 'end': 645, 'mesh': 'D003221'}, {'text': 'papilledema', 'type': 'Disease', 'start': 647, 'end': 658, 'mesh': 'D010211'}, {'text': 'somnolence', 'type': 'Disease', 'start': 660, 'end': 670, 'mesh': 'D006970'}, {'text': 'motor deficits', 'type': 'Disease', 'start': 688, 'end': 702, 'mesh': '-1'}, {'text': 'seizure', 'type': 'Disease', 'start': 726, 'end': 733, 'mesh': 'D012640'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 823, 'end': 836, 'mesh': 'D003907'}, {'text': 'tumor', 'type': 'Disease', 'start': 931, 'end': 936, 'mesh': 'D009369'}, {'text': 'edema', 'type': 'Disease', 'start': 956, 'end': 961, 'mesh': 'D004487'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1059, 'end': 1067, 'mesh': 'D064420'}, {'text': 'etoposide', 'type': 'Chemical', 'start': 1081, 'end': 1090, 'mesh': 'D005047'}, {'text': 'malignant glioma', 'type': 'Disease', 'start': 1103, 'end': 1119, 'mesh': 'D005910'}]"
+1203,3297909,Progressive bile duct injury after thiabendazole administration.,"A 27-yr-old man developed jaundice 2 wk after exposure to thiabendazole. Cholestasis persisted for 3 yr, at which time a liver transplant was performed. Two liver biopsy specimens and the hepatectomy specimen were remarkable for almost complete disappearance of interlobular bile ducts. Prominent fibrosis and hepatocellular regeneration were also present; however, the lobular architecture was preserved. This case represents an example of ""idiosyncratic"" drug-induced liver damage in which the primary target of injury is the bile duct. An autoimmune pathogenesis of the bile duct destruction is suggested.","[{'text': 'bile duct injury', 'type': 'Disease', 'start': 12, 'end': 28, 'mesh': 'D001649'}, {'text': 'thiabendazole', 'type': 'Chemical', 'start': 35, 'end': 48, 'mesh': 'D013827'}, {'text': 'jaundice', 'type': 'Disease', 'start': 91, 'end': 99, 'mesh': 'D007565'}, {'text': 'thiabendazole', 'type': 'Chemical', 'start': 123, 'end': 136, 'mesh': 'D013827'}, {'text': 'Cholestasis', 'type': 'Disease', 'start': 138, 'end': 149, 'mesh': 'D002779'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 362, 'end': 370, 'mesh': 'D005355'}, {'text': 'drug-induced liver damage', 'type': 'Disease', 'start': 522, 'end': 547, 'mesh': 'D056486'}, {'text': 'bile duct destruction', 'type': 'Disease', 'start': 638, 'end': 659, 'mesh': 'D001649'}]"
+1204,3323259,"Differential effects of 1,4-dihydropyridine calcium channel blockers: therapeutic implications.","Increasing recognition of the importance of calcium in the pathogenesis of cardiovascular disease has stimulated research into the use of calcium channel blocking agents for treatment of a variety of cardiovascular diseases. The favorable efficacy and tolerability profiles of these agents make them attractive therapeutic modalities. Clinical applications of calcium channel blockers parallel their tissue selectivity. In contrast to verapamil and diltiazem, which are roughly equipotent in their actions on the heart and vascular smooth muscle, the dihydropyridine calcium channel blockers are a group of potent peripheral vasodilator agents that exert minimal electrophysiologic effects on cardiac nodal or conduction tissue. As the first dihydropyridine available for use in the United States, nifedipine controls angina and hypertension with minimal depression of cardiac function. Additional members of this group of calcium channel blockers have been studied for a variety of indications for which they may offer advantages over current therapy. Once or twice daily dosage possible with nitrendipine and nisoldipine offers a convenient administration schedule, which encourages patient compliance in long-term therapy of hypertension. The coronary vasodilating properties of nisoldipine have led to the investigation of this agent for use in angina. Selectivity for the cerebrovascular bed makes nimodipine potentially useful in the treatment of subarachnoid hemorrhage, migraine headache, dementia, and stroke. In general, the dihydropyridine calcium channel blockers are usually well tolerated, with headache, facial flushing, palpitations, edema, nausea, anorexia, and dizziness being the more common adverse effects.","[{'text': '1,4-dihydropyridine', 'type': 'Chemical', 'start': 24, 'end': 43, 'mesh': 'C038806'}, {'text': 'calcium channel blockers', 'type': 'Chemical', 'start': 44, 'end': 68, 'mesh': 'D002121'}, {'text': 'calcium', 'type': 'Chemical', 'start': 140, 'end': 147, 'mesh': 'D002118'}, {'text': 'cardiovascular disease', 'type': 'Disease', 'start': 171, 'end': 193, 'mesh': 'D002318'}, {'text': 'calcium channel blocking agents', 'type': 'Chemical', 'start': 234, 'end': 265, 'mesh': 'D002121'}, {'text': 'cardiovascular diseases', 'type': 'Disease', 'start': 296, 'end': 319, 'mesh': 'D002318'}, {'text': 'calcium channel blockers', 'type': 'Chemical', 'start': 456, 'end': 480, 'mesh': 'D002121'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 531, 'end': 540, 'mesh': 'D014700'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 545, 'end': 554, 'mesh': 'D004110'}, {'text': 'dihydropyridine', 'type': 'Chemical', 'start': 647, 'end': 662, 'mesh': 'C038806'}, {'text': 'calcium channel blockers', 'type': 'Chemical', 'start': 663, 'end': 687, 'mesh': 'D002121'}, {'text': 'dihydropyridine', 'type': 'Chemical', 'start': 838, 'end': 853, 'mesh': 'C038806'}, {'text': 'nifedipine', 'type': 'Chemical', 'start': 894, 'end': 904, 'mesh': 'D009543'}, {'text': 'angina', 'type': 'Disease', 'start': 914, 'end': 920, 'mesh': 'D000787'}, {'text': 'hypertension', 'type': 'Disease', 'start': 925, 'end': 937, 'mesh': 'D006973'}, {'text': 'calcium channel blockers', 'type': 'Chemical', 'start': 1019, 'end': 1043, 'mesh': 'D002121'}, {'text': 'nitrendipine', 'type': 'Chemical', 'start': 1190, 'end': 1202, 'mesh': 'D009568'}, {'text': 'nisoldipine', 'type': 'Chemical', 'start': 1207, 'end': 1218, 'mesh': 'D015737'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1324, 'end': 1336, 'mesh': 'D006973'}, {'text': 'nisoldipine', 'type': 'Chemical', 'start': 1378, 'end': 1389, 'mesh': 'D015737'}, {'text': 'angina', 'type': 'Disease', 'start': 1445, 'end': 1451, 'mesh': 'D000787'}, {'text': 'nimodipine', 'type': 'Chemical', 'start': 1499, 'end': 1509, 'mesh': 'D009553'}, {'text': 'subarachnoid hemorrhage', 'type': 'Disease', 'start': 1549, 'end': 1572, 'mesh': 'D013345'}, {'text': 'migraine headache', 'type': 'Disease', 'start': 1574, 'end': 1591, 'mesh': 'D008881'}, {'text': 'dementia', 'type': 'Disease', 'start': 1593, 'end': 1601, 'mesh': 'D003704'}, {'text': 'stroke', 'type': 'Disease', 'start': 1607, 'end': 1613, 'mesh': 'D020521'}, {'text': 'dihydropyridine', 'type': 'Chemical', 'start': 1631, 'end': 1646, 'mesh': 'C038806'}, {'text': 'calcium channel blockers', 'type': 'Chemical', 'start': 1647, 'end': 1671, 'mesh': 'D002121'}, {'text': 'headache', 'type': 'Disease', 'start': 1705, 'end': 1713, 'mesh': 'D006261'}, {'text': 'flushing', 'type': 'Disease', 'start': 1722, 'end': 1730, 'mesh': 'D005483'}, {'text': 'palpitations', 'type': 'Disease', 'start': 1732, 'end': 1744, 'mesh': '-1'}, {'text': 'edema', 'type': 'Disease', 'start': 1746, 'end': 1751, 'mesh': 'D004487'}, {'text': 'nausea', 'type': 'Disease', 'start': 1753, 'end': 1759, 'mesh': 'D009325'}, {'text': 'anorexia', 'type': 'Disease', 'start': 1761, 'end': 1769, 'mesh': 'D000855'}, {'text': 'dizziness', 'type': 'Disease', 'start': 1775, 'end': 1784, 'mesh': 'D004244'}]"
+1205,3323599,The enhancement of aminonucleoside nephrosis by the co-administration of protamine.,"An experimental model of focal segmental glomerular sclerosis (FSGS) was developed in rats by the combined administration of puromycin-aminonucleoside (AMNS) and protamine sulfate (PS). Male Sprague-Dawley rats, uninephrectomized three weeks before, received daily injections of subcutaneous AMNS (1 mg/100 g body wt) and intravenous PS (2 separated doses of 2.5 mg/100 g body wt) for four days. The series of injections were repeated another three times at 10 day intervals. The animals were sacrificed on days 24, 52, and 80. They developed nephrotic syndrome and finally renal failure. The time-course curve of creatinine clearance dropped and showed significant difference (P less than 0.01) from that of each control group, such as, AMNS alone, PS alone or saline injected. Their glomeruli showed changes of progressive FSGS. The ultrastructural studies in the initial stage revealed significant lack of particles of perfused ruthenium red on the lamina rara externa and marked changes in epithelial cell cytoplasm. Therefore, it is suggested that the administration of PS enhances the toxicity of AMNS on the glomerulus and readily produces progressive FSGS in rats resulting in the end-stage renal disease.","[{'text': 'aminonucleoside', 'type': 'Chemical', 'start': 19, 'end': 34, 'mesh': 'D011692'}, {'text': 'nephrosis', 'type': 'Disease', 'start': 35, 'end': 44, 'mesh': 'D009401'}, {'text': 'focal segmental glomerular sclerosis', 'type': 'Disease', 'start': 109, 'end': 145, 'mesh': 'D005923'}, {'text': 'FSGS', 'type': 'Disease', 'start': 147, 'end': 151, 'mesh': 'D005923'}, {'text': 'puromycin-aminonucleoside', 'type': 'Chemical', 'start': 209, 'end': 234, 'mesh': 'D011692'}, {'text': 'AMNS', 'type': 'Chemical', 'start': 236, 'end': 240, 'mesh': 'D011692'}, {'text': 'protamine sulfate', 'type': 'Chemical', 'start': 246, 'end': 263, 'mesh': 'D011479'}, {'text': 'PS', 'type': 'Chemical', 'start': 265, 'end': 267, 'mesh': 'D011479'}, {'text': 'AMNS', 'type': 'Chemical', 'start': 376, 'end': 380, 'mesh': 'D011692'}, {'text': 'PS', 'type': 'Chemical', 'start': 418, 'end': 420, 'mesh': 'D011479'}, {'text': 'nephrotic syndrome', 'type': 'Disease', 'start': 627, 'end': 645, 'mesh': 'D009404'}, {'text': 'renal failure', 'type': 'Disease', 'start': 658, 'end': 671, 'mesh': 'D051437'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 698, 'end': 708, 'mesh': 'D003404'}, {'text': 'AMNS', 'type': 'Chemical', 'start': 822, 'end': 826, 'mesh': 'D011692'}, {'text': 'PS', 'type': 'Chemical', 'start': 834, 'end': 836, 'mesh': 'D011479'}, {'text': 'FSGS', 'type': 'Disease', 'start': 909, 'end': 913, 'mesh': 'D005923'}, {'text': 'ruthenium', 'type': 'Chemical', 'start': 1015, 'end': 1024, 'mesh': 'D012428'}, {'text': 'PS', 'type': 'Chemical', 'start': 1159, 'end': 1161, 'mesh': 'D011479'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1175, 'end': 1183, 'mesh': 'D064420'}, {'text': 'AMNS', 'type': 'Chemical', 'start': 1187, 'end': 1191, 'mesh': 'D011692'}, {'text': 'FSGS', 'type': 'Disease', 'start': 1243, 'end': 1247, 'mesh': 'D005923'}, {'text': 'end-stage renal disease', 'type': 'Disease', 'start': 1273, 'end': 1296, 'mesh': 'D007676'}]"
+1206,3339945,Theophylline neurotoxicity in pregnant rats.,The purpose of this investigation was to determine whether the neurotoxicity of theophylline is altered in advanced pregnancy. Sprague-Dawley rats that were 20 days pregnant and nonpregnant rats of the same age and strain received infusions of aminophylline until onset of maximal seizures which occurred after 28 and 30 minutes respectively. Theophylline concentrations at this endpoint in serum (total) and CSF were similar but serum (free) and brain concentrations were slightly different in pregnant rats. Theophylline serum protein binding determined by equilibrium dialysis was lower in pregnant rats. Fetal serum concentrations at onset of seizures in the mother were similar to maternal brain and CSF concentrations and correlated significantly with the former. It is concluded that advanced pregnancy has a negligible effect on the neurotoxic response to theophylline in rats.,"[{'text': 'Theophylline', 'type': 'Chemical', 'start': 0, 'end': 12, 'mesh': 'D013806'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 13, 'end': 26, 'mesh': 'D020258'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 108, 'end': 121, 'mesh': 'D020258'}, {'text': 'theophylline', 'type': 'Chemical', 'start': 125, 'end': 137, 'mesh': 'D013806'}, {'text': 'aminophylline', 'type': 'Chemical', 'start': 289, 'end': 302, 'mesh': 'D000628'}, {'text': 'seizures', 'type': 'Disease', 'start': 326, 'end': 334, 'mesh': 'D012640'}, {'text': 'Theophylline', 'type': 'Chemical', 'start': 388, 'end': 400, 'mesh': 'D013806'}, {'text': 'Theophylline', 'type': 'Chemical', 'start': 555, 'end': 567, 'mesh': 'D013806'}, {'text': 'seizures', 'type': 'Disease', 'start': 692, 'end': 700, 'mesh': 'D012640'}, {'text': 'neurotoxic', 'type': 'Disease', 'start': 886, 'end': 896, 'mesh': 'D020258'}, {'text': 'theophylline', 'type': 'Chemical', 'start': 909, 'end': 921, 'mesh': 'D013806'}]"
+1207,3375885,Hyperkalemia induced by indomethacin and naproxen and reversed by fludrocortisone.,"We have described a patient with severe rheumatoid arthritis and a history of mefenamic acid nephropathy in whom hyperkalemia and inappropriate hypoaldosteronism were caused by both indomethacin and naproxen, without major decline in renal function. It is likely that preexisting renal disease predisposed this patient to type IV renal tubular acidosis with prostaglandin synthetase inhibitors. Because he was unable to discontinue nonsteroidal anti-inflammatory drug therapy, fludrocortisone was added, correcting the hyperkalemia and allowing indomethacin therapy to be continued safely.","[{'text': 'Hyperkalemia', 'type': 'Disease', 'start': 0, 'end': 12, 'mesh': 'D006947'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 24, 'end': 36, 'mesh': 'D007213'}, {'text': 'naproxen', 'type': 'Chemical', 'start': 41, 'end': 49, 'mesh': 'D009288'}, {'text': 'fludrocortisone', 'type': 'Chemical', 'start': 66, 'end': 81, 'mesh': 'D005438'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 123, 'end': 143, 'mesh': 'D001172'}, {'text': 'mefenamic acid', 'type': 'Chemical', 'start': 161, 'end': 175, 'mesh': 'D008528'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 176, 'end': 187, 'mesh': 'D007674'}, {'text': 'hyperkalemia', 'type': 'Disease', 'start': 196, 'end': 208, 'mesh': 'D006947'}, {'text': 'hypoaldosteronism', 'type': 'Disease', 'start': 227, 'end': 244, 'mesh': 'D006994'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 265, 'end': 277, 'mesh': 'D007213'}, {'text': 'naproxen', 'type': 'Chemical', 'start': 282, 'end': 290, 'mesh': 'D009288'}, {'text': 'renal disease', 'type': 'Disease', 'start': 363, 'end': 376, 'mesh': 'D007674'}, {'text': 'type IV renal tubular acidosis', 'type': 'Disease', 'start': 405, 'end': 435, 'mesh': 'D006994'}, {'text': 'prostaglandin', 'type': 'Chemical', 'start': 441, 'end': 454, 'mesh': 'D011453'}, {'text': 'fludrocortisone', 'type': 'Chemical', 'start': 560, 'end': 575, 'mesh': 'D005438'}, {'text': 'hyperkalemia', 'type': 'Disease', 'start': 602, 'end': 614, 'mesh': 'D006947'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 628, 'end': 640, 'mesh': 'D007213'}]"
+1208,3383127,Hypotension as a manifestation of cardiotoxicity in three patients receiving cisplatin and 5-fluorouracil.,"Cardiac symptoms, including hypotension, developed in three patients with advanced colorectal carcinoma while being treated with cisplatin (CDDP) and 5-fluorouracil (5-FU). In two patients, hypotension was associated with severe left ventricular dysfunction. All three patients required therapy discontinuation. Cardiac enzymes remained normal despite transient electrocardiographic (EKG) changes. The presentation and cardiac evaluation (hemodynamic, echocardiographic, and scintigraphic) of these patients suggest new manifestations of 5-FU cardiotoxicity that may be influenced by CDDP. The possible pathophysiologic mechanisms are discussed.","[{'text': 'Hypotension', 'type': 'Disease', 'start': 0, 'end': 11, 'mesh': 'D007022'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 34, 'end': 48, 'mesh': 'D066126'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 77, 'end': 86, 'mesh': 'D002945'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 91, 'end': 105, 'mesh': 'D005472'}, {'text': 'hypotension', 'type': 'Disease', 'start': 135, 'end': 146, 'mesh': 'D007022'}, {'text': 'colorectal carcinoma', 'type': 'Disease', 'start': 190, 'end': 210, 'mesh': 'D015179'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 236, 'end': 245, 'mesh': 'D002945'}, {'text': 'CDDP', 'type': 'Chemical', 'start': 247, 'end': 251, 'mesh': 'D002945'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 257, 'end': 271, 'mesh': 'D005472'}, {'text': '5-FU', 'type': 'Chemical', 'start': 273, 'end': 277, 'mesh': 'D005472'}, {'text': 'hypotension', 'type': 'Disease', 'start': 297, 'end': 308, 'mesh': 'D007022'}, {'text': 'left ventricular dysfunction', 'type': 'Disease', 'start': 336, 'end': 364, 'mesh': 'D018487'}, {'text': '5-FU', 'type': 'Chemical', 'start': 645, 'end': 649, 'mesh': 'D005472'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 650, 'end': 664, 'mesh': 'D066126'}, {'text': 'CDDP', 'type': 'Chemical', 'start': 691, 'end': 695, 'mesh': 'D002945'}]"
+1209,3409843,Fatal aplastic anemia in a patient treated with carbamazepine.,"A case of fatal aplastic anemia due to carbamazepine treatment in an epileptic woman is reported. Despite concerns of fatal bone marrow toxicity due to carbamazepine, this is only the fourth documented and published report. Carbamazepine is a safe drug, but physicians and patients should be aware of the exceedingly rare but potentially fatal side effects, better prevented by clinical than by laboratory monitoring.","[{'text': 'aplastic anemia', 'type': 'Disease', 'start': 6, 'end': 21, 'mesh': 'D000741'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 48, 'end': 61, 'mesh': 'D002220'}, {'text': 'aplastic anemia', 'type': 'Disease', 'start': 79, 'end': 94, 'mesh': 'D000741'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 102, 'end': 115, 'mesh': 'D002220'}, {'text': 'epileptic', 'type': 'Disease', 'start': 132, 'end': 141, 'mesh': 'D004827'}, {'text': 'bone marrow toxicity', 'type': 'Disease', 'start': 187, 'end': 207, 'mesh': 'D001855'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 215, 'end': 228, 'mesh': 'D002220'}, {'text': 'Carbamazepine', 'type': 'Chemical', 'start': 287, 'end': 300, 'mesh': 'D002220'}]"
+1210,3423103,Participation of a bulbospinal serotonergic pathway in the rat brain in clonidine-induced hypotension and bradycardia.,"The effects of microinjection of clonidine (1-10 micrograms in 1 microliter) into a region adjacent to the ventrolateral surface of the medulla oblongata on cardiovascular function were assessed in urethane-anesthetized rats. Intramedullary administration of clonidine, but not saline vehicle, caused a dose-dependent decrease in both the mean arterial pressure and the heart rate. The clonidine-induced hypotension was antagonized by prior spinal transection, but not bilateral vagotomy. On the other hand, the clonidine-induced bradycardia was antagonized by prior bilateral vagotomy, but not spinal transection. Furthermore, selective destruction of the spinal 5-HT nerves, produced by bilateral spinal injection of 5,7-dihydroxytryptamine, reduced the magnitude of the vasodepressor or the bradycardiac responses to clonidine microinjected into the area near the ventrolateral surface of the medulla oblongata in rats. The data indicate that a bulbospinal serotonergic pathway is involved in development of clonidine-induced hypotension and bradycardia. The induced hypotension is brought about by a decrease in sympathetic efferent activity, whereas the induced bradycardia was due to an increase in vagal efferent activity.","[{'text': 'clonidine', 'type': 'Chemical', 'start': 72, 'end': 81, 'mesh': 'D003000'}, {'text': 'hypotension', 'type': 'Disease', 'start': 90, 'end': 101, 'mesh': 'D007022'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 106, 'end': 117, 'mesh': 'D001919'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 152, 'end': 161, 'mesh': 'D003000'}, {'text': 'urethane', 'type': 'Chemical', 'start': 317, 'end': 325, 'mesh': 'D014520'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 378, 'end': 387, 'mesh': 'D003000'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 505, 'end': 514, 'mesh': 'D003000'}, {'text': 'hypotension', 'type': 'Disease', 'start': 523, 'end': 534, 'mesh': 'D007022'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 631, 'end': 640, 'mesh': 'D003000'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 649, 'end': 660, 'mesh': 'D001919'}, {'text': '5-HT', 'type': 'Chemical', 'start': 783, 'end': 787, 'mesh': 'D012701'}, {'text': '5,7-dihydroxytryptamine', 'type': 'Chemical', 'start': 838, 'end': 861, 'mesh': 'D015116'}, {'text': 'bradycardiac', 'type': 'Disease', 'start': 913, 'end': 925, 'mesh': 'D001919'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 939, 'end': 948, 'mesh': 'D003000'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 1130, 'end': 1139, 'mesh': 'D003000'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1148, 'end': 1159, 'mesh': 'D007022'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 1164, 'end': 1175, 'mesh': 'D001919'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1189, 'end': 1200, 'mesh': 'D007022'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 1286, 'end': 1297, 'mesh': 'D001919'}]"
+1211,3439580,Hypertension in neuroblastoma induced by imipramine.,"Hypertension is a well-known finding in some patients with neuroblastoma. However, it has not previously been described in association with the use of Imipramine. We report the occurrence of severe hypertension (blood pressure 190/160) in a 4-year-old girl with neuroblastoma who was given Imipramine to control a behavior disorder. It was determined later that this patient's tumor was recurring at the time of her hypertensive episode. Since she had no blood pressure elevation at initial diagnosis and none following discontinuation of the Imipramine (when she was in florid relapse), we believe that this drug rather than her underlying disease alone caused her hypertension. The mechanism for this reaction is believed to be increased levels of vasoactive catecholamines due to interference of their physiologic inactivation by Imipramine. From this experience, we urge extreme caution in the use of tricyclic antidepressants in children with active neuroblastoma.","[{'text': 'Hypertension', 'type': 'Disease', 'start': 0, 'end': 12, 'mesh': 'D006973'}, {'text': 'neuroblastoma', 'type': 'Disease', 'start': 16, 'end': 29, 'mesh': 'D009447'}, {'text': 'imipramine', 'type': 'Chemical', 'start': 41, 'end': 51, 'mesh': 'D007099'}, {'text': 'Hypertension', 'type': 'Disease', 'start': 53, 'end': 65, 'mesh': 'D006973'}, {'text': 'neuroblastoma', 'type': 'Disease', 'start': 112, 'end': 125, 'mesh': 'D009447'}, {'text': 'Imipramine', 'type': 'Chemical', 'start': 204, 'end': 214, 'mesh': 'D007099'}, {'text': 'hypertension', 'type': 'Disease', 'start': 251, 'end': 263, 'mesh': 'D006973'}, {'text': 'neuroblastoma', 'type': 'Disease', 'start': 315, 'end': 328, 'mesh': 'D009447'}, {'text': 'Imipramine', 'type': 'Chemical', 'start': 343, 'end': 353, 'mesh': 'D007099'}, {'text': 'behavior disorder', 'type': 'Disease', 'start': 367, 'end': 384, 'mesh': 'D002653'}, {'text': 'tumor', 'type': 'Disease', 'start': 430, 'end': 435, 'mesh': 'D009369'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 469, 'end': 481, 'mesh': 'D006973'}, {'text': 'Imipramine', 'type': 'Chemical', 'start': 596, 'end': 606, 'mesh': 'D007099'}, {'text': 'hypertension', 'type': 'Disease', 'start': 719, 'end': 731, 'mesh': 'D006973'}, {'text': 'catecholamines', 'type': 'Chemical', 'start': 814, 'end': 828, 'mesh': 'D002395'}, {'text': 'Imipramine', 'type': 'Chemical', 'start': 886, 'end': 896, 'mesh': 'D007099'}, {'text': 'neuroblastoma', 'type': 'Disease', 'start': 1008, 'end': 1021, 'mesh': 'D009447'}]"
+1212,3475563,Rechallenge of patients who developed oral candidiasis or hoarseness with beclomethasone dipropionate.,"Of 158 asthmatic patients who were placed on inhaled beclomethasone, 15 (9.5%) developed either hoarseness (8), oral thrush (6), or both (1). When their adverse reactions subsided, seven of these 15 patients were rechallenged with inhaled beclomethasone. These included five cases who developed hoarseness and three who developed Candidiasis. One patient had both. Oral thrush did not recur, but 60% (3/5) of patients with hoarseness had recurrence. We conclude that patients may be restarted on inhaled beclomethasone when clinically indicated; however, because of the high recurrence rate, patients who develop hoarseness should not be re-challenged. Concomitant use of oral prednisone and topical beclomethasone may increase the risk of developing hoarseness or candidiasis.","[{'text': 'oral candidiasis', 'type': 'Disease', 'start': 38, 'end': 54, 'mesh': 'D002180'}, {'text': 'hoarseness', 'type': 'Disease', 'start': 58, 'end': 68, 'mesh': 'D006685'}, {'text': 'beclomethasone dipropionate', 'type': 'Chemical', 'start': 74, 'end': 101, 'mesh': 'D001507'}, {'text': 'asthmatic', 'type': 'Disease', 'start': 110, 'end': 119, 'mesh': 'D001249'}, {'text': 'beclomethasone', 'type': 'Chemical', 'start': 156, 'end': 170, 'mesh': 'D001507'}, {'text': 'hoarseness', 'type': 'Disease', 'start': 199, 'end': 209, 'mesh': 'D006685'}, {'text': 'thrush', 'type': 'Disease', 'start': 220, 'end': 226, 'mesh': 'D002180'}, {'text': 'beclomethasone', 'type': 'Chemical', 'start': 342, 'end': 356, 'mesh': 'D001507'}, {'text': 'hoarseness', 'type': 'Disease', 'start': 398, 'end': 408, 'mesh': 'D006685'}, {'text': 'Candidiasis', 'type': 'Disease', 'start': 433, 'end': 444, 'mesh': 'D002177'}, {'text': 'thrush', 'type': 'Disease', 'start': 473, 'end': 479, 'mesh': 'D002180'}, {'text': 'hoarseness', 'type': 'Disease', 'start': 526, 'end': 536, 'mesh': 'D006685'}, {'text': 'beclomethasone', 'type': 'Chemical', 'start': 607, 'end': 621, 'mesh': 'D001507'}, {'text': 'hoarseness', 'type': 'Disease', 'start': 716, 'end': 726, 'mesh': 'D006685'}, {'text': 'prednisone', 'type': 'Chemical', 'start': 780, 'end': 790, 'mesh': 'D011241'}, {'text': 'beclomethasone', 'type': 'Chemical', 'start': 803, 'end': 817, 'mesh': 'D001507'}, {'text': 'hoarseness', 'type': 'Disease', 'start': 854, 'end': 864, 'mesh': 'D006685'}, {'text': 'candidiasis', 'type': 'Disease', 'start': 868, 'end': 879, 'mesh': 'D002177'}]"
+1213,3533179,Cyclophosphamide cardiotoxicity: an analysis of dosing as a risk factor.,"Patients who undergo bone marrow transplantation are generally immunosuppressed with a dose of cyclophosphamide (CYA) which is usually calculated based on the patient's weight. At these high doses of CYA, serious cardiotoxicity may occur, but definitive risk factors for the development of such cardiotoxicity have not been described. Since chemotherapeutic agent toxicity generally correlates with dose per body surface area, we retrospectively calculated the dose of CYA in patients transplanted at our institution to determine whether the incidence of CYA cardiotoxicity correlated with the dose per body surface area. Eighty patients who were to receive CYA 50 mg/kg/d for four days as preparation for marrow grafting underwent a total of 84 transplants for aplastic anemia, Wiskott-Aldrich syndrome, or severe combined immunodeficiency syndrome. Fourteen of 84 (17%) patients had symptoms and signs consistent with CYA cardiotoxicity within ten days of receiving 1 to 4 doses of CYA. Six of the 14 patients died with congestive heart failure. The dose of CYA per body surface area was calculated for all patients and the patients were divided into two groups based on daily CYA dose: Group 1, CYA less than or equal to 1.55 g/m2/d; Group 2, CYA greater than 1.55 g/m2/d. Cardiotoxicity that was thought to be related to CYA occurred in 1/32 (3%) of patients in Group 1 and in 13/52 (25%) patients in Group 2 (P less than 0.025). Congestive heart failure caused or contributed to death in 0/32 patients in Group 1 v 6/52 (12%) of patients in Group 2 (P less than 0.25). There was no difference in the rate of engraftment of evaluable patients in the two groups (P greater than 0.5). We conclude that the CYA cardiotoxicity correlates with CYA dosage as calculated by body surface area, and that patients with aplastic anemia and immunodeficiencies can be effectively prepared for bone marrow grafting at a CYA dose of 1.55 g/m2/d for four days with a lower incidence of cardiotoxicity than patients whose CYA dosage is calculated based on weight. This study reaffirms the principle that drug toxicity correlates with dose per body surface area.","[{'text': 'Cyclophosphamide', 'type': 'Chemical', 'start': 0, 'end': 16, 'mesh': 'D003520'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 17, 'end': 31, 'mesh': 'D066126'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 168, 'end': 184, 'mesh': 'D003520'}, {'text': 'CYA', 'type': 'Chemical', 'start': 186, 'end': 189, 'mesh': 'D003520'}, {'text': 'CYA', 'type': 'Chemical', 'start': 273, 'end': 276, 'mesh': 'D003520'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 286, 'end': 300, 'mesh': 'D066126'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 368, 'end': 382, 'mesh': 'D066126'}, {'text': 'toxicity', 'type': 'Disease', 'start': 437, 'end': 445, 'mesh': 'D064420'}, {'text': 'CYA', 'type': 'Chemical', 'start': 542, 'end': 545, 'mesh': 'D003520'}, {'text': 'CYA', 'type': 'Chemical', 'start': 628, 'end': 631, 'mesh': 'D003520'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 632, 'end': 646, 'mesh': 'D066126'}, {'text': 'CYA', 'type': 'Chemical', 'start': 731, 'end': 734, 'mesh': 'D003520'}, {'text': 'aplastic anemia', 'type': 'Disease', 'start': 835, 'end': 850, 'mesh': 'D000741'}, {'text': 'Wiskott-Aldrich syndrome', 'type': 'Disease', 'start': 852, 'end': 876, 'mesh': 'D014923'}, {'text': 'severe combined immunodeficiency syndrome', 'type': 'Disease', 'start': 881, 'end': 922, 'mesh': 'D016511'}, {'text': 'CYA', 'type': 'Chemical', 'start': 993, 'end': 996, 'mesh': 'D003520'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 997, 'end': 1011, 'mesh': 'D066126'}, {'text': 'CYA', 'type': 'Chemical', 'start': 1057, 'end': 1060, 'mesh': 'D003520'}, {'text': 'congestive heart failure', 'type': 'Disease', 'start': 1095, 'end': 1119, 'mesh': 'D006333'}, {'text': 'CYA', 'type': 'Chemical', 'start': 1133, 'end': 1136, 'mesh': 'D003520'}, {'text': 'CYA', 'type': 'Chemical', 'start': 1252, 'end': 1255, 'mesh': 'D003520'}, {'text': 'CYA', 'type': 'Chemical', 'start': 1271, 'end': 1274, 'mesh': 'D003520'}, {'text': 'CYA', 'type': 'Chemical', 'start': 1319, 'end': 1322, 'mesh': 'D003520'}, {'text': 'Cardiotoxicity', 'type': 'Disease', 'start': 1349, 'end': 1363, 'mesh': 'D066126'}, {'text': 'CYA', 'type': 'Chemical', 'start': 1398, 'end': 1401, 'mesh': 'D003520'}, {'text': 'Congestive heart failure', 'type': 'Disease', 'start': 1507, 'end': 1531, 'mesh': 'D006333'}, {'text': 'CYA', 'type': 'Chemical', 'start': 1781, 'end': 1784, 'mesh': 'D003520'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1785, 'end': 1799, 'mesh': 'D066126'}, {'text': 'CYA', 'type': 'Chemical', 'start': 1816, 'end': 1819, 'mesh': 'D003520'}, {'text': 'aplastic anemia', 'type': 'Disease', 'start': 1886, 'end': 1901, 'mesh': 'D000741'}, {'text': 'immunodeficiencies', 'type': 'Disease', 'start': 1906, 'end': 1924, 'mesh': 'D007153'}, {'text': 'CYA', 'type': 'Chemical', 'start': 1983, 'end': 1986, 'mesh': 'D003520'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 2047, 'end': 2061, 'mesh': 'D066126'}, {'text': 'CYA', 'type': 'Chemical', 'start': 2082, 'end': 2085, 'mesh': 'D003520'}, {'text': 'toxicity', 'type': 'Disease', 'start': 2169, 'end': 2177, 'mesh': 'D064420'}]"
+1214,3538855,Studies of risk factors for aminoglycoside nephrotoxicity.,"The epidemiology of aminoglycoside-induced nephrotoxicity is not fully understood. Experimental studies in healthy human volunteers indicate aminoglycosides cause proximal tubular damage in most patients, but rarely, if ever, cause glomerular or tubular dysfunction. Clinical trials of aminoglycosides in seriously ill patients indicate that the relative risk for developing acute renal failure during therapy ranges from 8 to 10 and that the attributable risk is 70% to 80%. Further analysis of these data suggests that the duration of therapy, plasma aminoglycoside levels, liver disease, advanced age, high initial estimated creatinine clearance and, possibly, female gender all increase the risk for nephrotoxicity. Other causes of acute renal failure, such as shock, appear to have an additive effect. Predictive models have been developed from these analyses that should be useful for identifying patients at high risk. These models may also be useful in developing insights into the pathophysiology of aminoglycoside-induced nephrotoxicity.","[{'text': 'aminoglycoside', 'type': 'Chemical', 'start': 28, 'end': 42, 'mesh': 'D000617'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 43, 'end': 57, 'mesh': 'D007674'}, {'text': 'aminoglycoside', 'type': 'Chemical', 'start': 79, 'end': 93, 'mesh': 'D000617'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 102, 'end': 116, 'mesh': 'D007674'}, {'text': 'aminoglycosides', 'type': 'Chemical', 'start': 200, 'end': 215, 'mesh': 'D000617'}, {'text': 'glomerular or tubular dysfunction', 'type': 'Disease', 'start': 291, 'end': 324, 'mesh': 'D007674'}, {'text': 'aminoglycosides', 'type': 'Chemical', 'start': 345, 'end': 360, 'mesh': 'D000617'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 434, 'end': 453, 'mesh': 'D058186'}, {'text': 'aminoglycoside', 'type': 'Chemical', 'start': 612, 'end': 626, 'mesh': 'D000617'}, {'text': 'liver disease', 'type': 'Disease', 'start': 635, 'end': 648, 'mesh': 'D008107'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 687, 'end': 697, 'mesh': 'D003404'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 763, 'end': 777, 'mesh': 'D007674'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 795, 'end': 814, 'mesh': 'D058186'}, {'text': 'shock', 'type': 'Disease', 'start': 824, 'end': 829, 'mesh': 'D012769'}, {'text': 'aminoglycoside', 'type': 'Chemical', 'start': 1068, 'end': 1082, 'mesh': 'D000617'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1091, 'end': 1105, 'mesh': 'D007674'}]"
+1215,3685052,Flurothyl seizure thresholds in mice treated neonatally with a single injection of monosodium glutamate (MSG): evaluation of experimental parameters in flurothyl seizure testing.,"Monosodium glutamate (MSG) administration to neonatal rodents produces convulsions and results in numerous biochemical and behavioral deficits. These studies were undertaken to determine if neonatal administration of MSG produced permanent alterations in seizure susceptibility, since previous investigations were inconclusive. A flurothyl ether seizure screening technique was used to evaluate seizure susceptibility in adult mice that received neonatal injections of MSG (4 mg/g and 1 mg/g). MSG treatment resulted in significant reductions in whole brain weight but did not alter seizure threshold. A naloxone (5 mg/kg) challenge was also ineffective in altering the seizure thresholds of either control of MSG-treated mice. Flurothyl ether produced hypothermia which was correlated with the duration of flurothyl exposure; however, the relationship of hypothermia to seizure induction was unclear. Flurothyl seizure testing proved to be a rapid and reliable technique with which to evaluate seizure susceptibility.","[{'text': 'Flurothyl', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D005481'}, {'text': 'seizure', 'type': 'Disease', 'start': 10, 'end': 17, 'mesh': 'D012640'}, {'text': 'monosodium glutamate', 'type': 'Chemical', 'start': 83, 'end': 103, 'mesh': 'D012970'}, {'text': 'MSG', 'type': 'Chemical', 'start': 105, 'end': 108, 'mesh': 'D012970'}, {'text': 'flurothyl', 'type': 'Chemical', 'start': 152, 'end': 161, 'mesh': 'D005481'}, {'text': 'seizure', 'type': 'Disease', 'start': 162, 'end': 169, 'mesh': 'D012640'}, {'text': 'Monosodium glutamate', 'type': 'Chemical', 'start': 179, 'end': 199, 'mesh': 'D012970'}, {'text': 'MSG', 'type': 'Chemical', 'start': 201, 'end': 204, 'mesh': 'D012970'}, {'text': 'convulsions', 'type': 'Disease', 'start': 250, 'end': 261, 'mesh': 'D012640'}, {'text': 'MSG', 'type': 'Chemical', 'start': 396, 'end': 399, 'mesh': 'D012970'}, {'text': 'seizure', 'type': 'Disease', 'start': 434, 'end': 441, 'mesh': 'D012640'}, {'text': 'flurothyl', 'type': 'Chemical', 'start': 509, 'end': 518, 'mesh': 'D005481'}, {'text': 'ether', 'type': 'Chemical', 'start': 519, 'end': 524, 'mesh': 'D004986'}, {'text': 'seizure', 'type': 'Disease', 'start': 525, 'end': 532, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 574, 'end': 581, 'mesh': 'D012640'}, {'text': 'MSG', 'type': 'Chemical', 'start': 648, 'end': 651, 'mesh': 'D012970'}, {'text': 'MSG', 'type': 'Chemical', 'start': 673, 'end': 676, 'mesh': 'D012970'}, {'text': 'seizure', 'type': 'Disease', 'start': 762, 'end': 769, 'mesh': 'D012640'}, {'text': 'naloxone', 'type': 'Chemical', 'start': 783, 'end': 791, 'mesh': 'D009270'}, {'text': 'seizure', 'type': 'Disease', 'start': 849, 'end': 856, 'mesh': 'D012640'}, {'text': 'MSG', 'type': 'Chemical', 'start': 889, 'end': 892, 'mesh': 'D012970'}, {'text': 'Flurothyl', 'type': 'Chemical', 'start': 907, 'end': 916, 'mesh': 'D005481'}, {'text': 'ether', 'type': 'Chemical', 'start': 917, 'end': 922, 'mesh': 'D004986'}, {'text': 'hypothermia', 'type': 'Disease', 'start': 932, 'end': 943, 'mesh': 'D007035'}, {'text': 'flurothyl', 'type': 'Chemical', 'start': 986, 'end': 995, 'mesh': 'D005481'}, {'text': 'hypothermia', 'type': 'Disease', 'start': 1035, 'end': 1046, 'mesh': 'D007035'}, {'text': 'seizure', 'type': 'Disease', 'start': 1050, 'end': 1057, 'mesh': 'D012640'}, {'text': 'Flurothyl', 'type': 'Chemical', 'start': 1081, 'end': 1090, 'mesh': 'D005481'}, {'text': 'seizure', 'type': 'Disease', 'start': 1091, 'end': 1098, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 1174, 'end': 1181, 'mesh': 'D012640'}]"
+1216,3708328,Susceptibility to seizures produced by pilocarpine in rats after microinjection of isoniazid or gamma-vinyl-GABA into the substantia nigra.,"Pilocarpine, given intraperitoneally to rats, reproduces the neuropathological sequelae of temporal lobe epilepsy and provides a relevant animal model for studying mechanisms of buildup of convulsive activity and pathways operative in the generalization and propagation of seizures within the forebrain. In the present study, the effects of manipulating the activity of the gamma-aminobutyric acid (GABA)-mediated synaptic inhibition within the substantia nigra on seizures produced by pilocarpine in rats, were investigated. In animals pretreated with microinjections of isoniazid, 150 micrograms, an inhibitor of activity of the GABA-synthesizing enzyme, L-glutamic acid decarboxylase, into the substantia nigra pars reticulata (SNR), bilaterally, non-convulsant doses of pilocarpine, 100 and 200 mg/kg, resulted in severe motor limbic seizures and status epilepticus. Electroencephalographic and behavioral monitoring revealed a profound reduction of the threshold for pilocarpine-induced convulsions. Morphological analysis of frontal forebrain sections with light microscopy revealed seizure-related damage to the hippocampal formation, thalamus, amygdala, olfactory cortex, substantia nigra and neocortex, which is typically observed with pilocarpine in doses exceeding 350 mg/kg. Bilateral intrastriatal injections of isoniazid did not augment seizures produced by pilocarpine, 200 mg/kg. Application of an irreversible inhibitor of GABA transaminase, gamma-vinyl-GABA (D,L-4-amino-hex-5-enoic acid), 5 micrograms, into the SNR, bilaterally, suppressed the appearance of electrographic and behavioral seizures produced by pilocarpine, 380 mg/kg. This treatment was also sufficient to protect animals from the occurrence of brain damage. Microinjections of gamma-vinyl-GABA, 5 micrograms, into the dorsal striatum, bilaterally, failed to prevent the development of convulsions produced by pilocarpine, 380 mg/kg. The results demonstrate that the threshold for pilocarpine-induced seizures in rats is subjected to the regulation of the GABA-mediated synaptic inhibition within the substantia nigra.","[{'text': 'seizures', 'type': 'Disease', 'start': 18, 'end': 26, 'mesh': 'D012640'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 39, 'end': 50, 'mesh': 'D010862'}, {'text': 'isoniazid', 'type': 'Chemical', 'start': 83, 'end': 92, 'mesh': 'D007538'}, {'text': 'gamma-vinyl-GABA', 'type': 'Chemical', 'start': 96, 'end': 112, 'mesh': 'D020888'}, {'text': 'Pilocarpine', 'type': 'Chemical', 'start': 140, 'end': 151, 'mesh': 'D010862'}, {'text': 'temporal lobe epilepsy', 'type': 'Disease', 'start': 231, 'end': 253, 'mesh': 'D004833'}, {'text': 'convulsive', 'type': 'Disease', 'start': 329, 'end': 339, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 413, 'end': 421, 'mesh': 'D012640'}, {'text': 'gamma-aminobutyric acid', 'type': 'Chemical', 'start': 514, 'end': 537, 'mesh': 'D005680'}, {'text': 'GABA', 'type': 'Chemical', 'start': 539, 'end': 543, 'mesh': 'D005680'}, {'text': 'seizures', 'type': 'Disease', 'start': 605, 'end': 613, 'mesh': 'D012640'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 626, 'end': 637, 'mesh': 'D010862'}, {'text': 'isoniazid', 'type': 'Chemical', 'start': 712, 'end': 721, 'mesh': 'D007538'}, {'text': 'GABA', 'type': 'Chemical', 'start': 771, 'end': 775, 'mesh': 'D005680'}, {'text': 'L-glutamic acid', 'type': 'Chemical', 'start': 797, 'end': 812, 'mesh': 'D018698'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 914, 'end': 925, 'mesh': 'D010862'}, {'text': 'seizures', 'type': 'Disease', 'start': 978, 'end': 986, 'mesh': 'D012640'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 991, 'end': 1009, 'mesh': 'D013226'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1112, 'end': 1123, 'mesh': 'D010862'}, {'text': 'convulsions', 'type': 'Disease', 'start': 1132, 'end': 1143, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 1229, 'end': 1236, 'mesh': 'D012640'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1385, 'end': 1396, 'mesh': 'D010862'}, {'text': 'isoniazid', 'type': 'Chemical', 'start': 1465, 'end': 1474, 'mesh': 'D007538'}, {'text': 'seizures', 'type': 'Disease', 'start': 1491, 'end': 1499, 'mesh': 'D012640'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1512, 'end': 1523, 'mesh': 'D010862'}, {'text': 'GABA', 'type': 'Chemical', 'start': 1580, 'end': 1584, 'mesh': 'D005680'}, {'text': 'gamma-vinyl-GABA', 'type': 'Chemical', 'start': 1599, 'end': 1615, 'mesh': 'D020888'}, {'text': 'D,L-4-amino-hex-5-enoic acid', 'type': 'Chemical', 'start': 1617, 'end': 1645, 'mesh': 'D020888'}, {'text': 'seizures', 'type': 'Disease', 'start': 1748, 'end': 1756, 'mesh': 'D012640'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1769, 'end': 1780, 'mesh': 'D010862'}, {'text': 'brain damage', 'type': 'Disease', 'start': 1870, 'end': 1882, 'mesh': 'D001930'}, {'text': 'gamma-vinyl-GABA', 'type': 'Chemical', 'start': 1903, 'end': 1919, 'mesh': 'D020888'}, {'text': 'convulsions', 'type': 'Disease', 'start': 2011, 'end': 2022, 'mesh': 'D012640'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 2035, 'end': 2046, 'mesh': 'D010862'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 2106, 'end': 2117, 'mesh': 'D010862'}, {'text': 'seizures', 'type': 'Disease', 'start': 2126, 'end': 2134, 'mesh': 'D012640'}, {'text': 'GABA', 'type': 'Chemical', 'start': 2181, 'end': 2185, 'mesh': 'D005680'}]"
+1217,3746148,Non-invasive detection of coronary artery disease by body surface electrocardiographic mapping after dipyridamole infusion.,"Electrocardiographic changes after dipyridamole infusion (0.568 mg/kg/4 min) were studied in 41 patients with coronary artery disease and compared with those after submaximal treadmill exercise by use of the body surface mapping technique. Patients were divided into three groups; 19 patients without myocardial infarction (non-MI group), 14 with anterior infarction (ANT-MI) and eight with inferior infarction (INF-MI). Eighty-seven unipolar electrocardiograms (ECGs) distributed over the entire thoracic surface were simultaneously recorded. After dipyridamole, ischemic ST-segment depression (0.05 mV or more) was observed in 84% of the non-MI group, 29% of the ANT-MI group, 63% of the INF-MI group and 61% of the total population. Exercise-induced ST depression was observed in 84% of the non-MI group, 43% of the ANT-MI group, 38% of the INF-MI group and 61% of the total. For individual patients, there were no obvious differences between the body surface distribution of ST depression in both tests. The increase in pressure rate product after dipyridamole was significantly less than that during the treadmill exercise. The data suggest that the dipyridamole-induced myocardial ischemia is caused by the inhomogenous distribution of myocardial blood flow. We conclude that the dipyridamole ECG test is as useful as the exercise ECG test for the assessment of coronary artery disease.","[{'text': 'coronary artery disease', 'type': 'Disease', 'start': 26, 'end': 49, 'mesh': 'D003324'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 101, 'end': 113, 'mesh': 'D004176'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 159, 'end': 171, 'mesh': 'D004176'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 234, 'end': 257, 'mesh': 'D003324'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 425, 'end': 446, 'mesh': 'D009203'}, {'text': 'MI', 'type': 'Disease', 'start': 452, 'end': 454, 'mesh': 'D009203'}, {'text': 'anterior infarction', 'type': 'Disease', 'start': 471, 'end': 490, 'mesh': 'D056988'}, {'text': 'ANT-MI', 'type': 'Disease', 'start': 492, 'end': 498, 'mesh': 'D056988'}, {'text': 'inferior infarction', 'type': 'Disease', 'start': 515, 'end': 534, 'mesh': 'D056989'}, {'text': 'INF-MI', 'type': 'Disease', 'start': 536, 'end': 542, 'mesh': 'D056989'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 674, 'end': 686, 'mesh': 'D004176'}, {'text': 'ischemic', 'type': 'Disease', 'start': 688, 'end': 696, 'mesh': 'D007511'}, {'text': 'depression', 'type': 'Disease', 'start': 708, 'end': 718, 'mesh': 'D003866'}, {'text': 'MI', 'type': 'Disease', 'start': 768, 'end': 770, 'mesh': 'D009203'}, {'text': 'ANT-MI', 'type': 'Disease', 'start': 789, 'end': 795, 'mesh': 'D056988'}, {'text': 'INF-MI', 'type': 'Disease', 'start': 814, 'end': 820, 'mesh': 'D056989'}, {'text': 'depression', 'type': 'Disease', 'start': 880, 'end': 890, 'mesh': 'D003866'}, {'text': 'MI', 'type': 'Disease', 'start': 922, 'end': 924, 'mesh': 'D009203'}, {'text': 'ANT-MI', 'type': 'Disease', 'start': 943, 'end': 949, 'mesh': 'D056988'}, {'text': 'INF-MI', 'type': 'Disease', 'start': 968, 'end': 974, 'mesh': 'D056989'}, {'text': 'depression', 'type': 'Disease', 'start': 1106, 'end': 1116, 'mesh': 'D003866'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 1176, 'end': 1188, 'mesh': 'D004176'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 1279, 'end': 1291, 'mesh': 'D004176'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 1300, 'end': 1319, 'mesh': 'D017202'}, {'text': 'dipyridamole', 'type': 'Chemical', 'start': 1410, 'end': 1422, 'mesh': 'D004176'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 1492, 'end': 1515, 'mesh': 'D003324'}]"
+1218,3798047,Bradycardia after high-dose intravenous methylprednisolone therapy.,"In 5 consecutive patients with rheumatoid arthritis who received intravenous high-dose methylprednisolone (MP) therapy (1 g daily for 2 or 3 consecutive days), a decline in pulse rate was observed, most pronounced on day 4. In one of the 5 patients the bradycardia was associated with complaints of substernal pressure. Reversal to normal heart rate was found on day 7. Electrocardiographic registrations showed sinus bradycardia in all cases. No significant changes in plasma concentrations of electrolytes were found. Careful observation of patients receiving high-dose MP is recommended. High-dose MP may be contraindicated in patients with known heart disease.","[{'text': 'Bradycardia', 'type': 'Disease', 'start': 0, 'end': 11, 'mesh': 'D001919'}, {'text': 'methylprednisolone', 'type': 'Chemical', 'start': 40, 'end': 58, 'mesh': 'D008775'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 99, 'end': 119, 'mesh': 'D001172'}, {'text': 'methylprednisolone', 'type': 'Chemical', 'start': 155, 'end': 173, 'mesh': 'D008775'}, {'text': 'MP', 'type': 'Chemical', 'start': 175, 'end': 177, 'mesh': 'D008775'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 321, 'end': 332, 'mesh': 'D001919'}, {'text': 'sinus bradycardia', 'type': 'Disease', 'start': 480, 'end': 497, 'mesh': 'D012804'}, {'text': 'MP', 'type': 'Chemical', 'start': 640, 'end': 642, 'mesh': 'D008775'}, {'text': 'MP', 'type': 'Chemical', 'start': 669, 'end': 671, 'mesh': 'D008775'}, {'text': 'heart disease', 'type': 'Disease', 'start': 718, 'end': 731, 'mesh': 'D006331'}]"
+1219,3812624,Two cases of downbeat nystagmus and oscillopsia associated with carbamazepine.,"Downbeat nystagmus is often associated with structural lesions at the craniocervical junction, but has occasionally been reported as a manifestation of metabolic imbalance or drug intoxication. We recorded the eye movements of two patients with reversible downbeat nystagmus related to carbamazepine therapy. The nystagmus of both patients resolved after reduction of the serum carbamazepine levels. Neuroradiologic investigations including magnetic resonance imaging scans in both patients showed no evidence of intracranial abnormality. In patients with downbeat nystagmus who are taking anticonvulsant medications, consideration should be given to reduction in dose before further investigation is undertaken.","[{'text': 'downbeat nystagmus', 'type': 'Disease', 'start': 13, 'end': 31, 'mesh': 'D009759'}, {'text': 'oscillopsia', 'type': 'Disease', 'start': 36, 'end': 47, 'mesh': 'D015835'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 64, 'end': 77, 'mesh': 'D002220'}, {'text': 'Downbeat nystagmus', 'type': 'Disease', 'start': 79, 'end': 97, 'mesh': 'D009759'}, {'text': 'downbeat nystagmus', 'type': 'Disease', 'start': 335, 'end': 353, 'mesh': 'D009759'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 365, 'end': 378, 'mesh': 'D002220'}, {'text': 'nystagmus', 'type': 'Disease', 'start': 392, 'end': 401, 'mesh': 'D009759'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 457, 'end': 470, 'mesh': 'D002220'}, {'text': 'downbeat nystagmus', 'type': 'Disease', 'start': 635, 'end': 653, 'mesh': 'D009759'}]"
+1220,3831029,Improvement by denopamine (TA-064) of pentobarbital-induced cardiac failure in the dog heart-lung preparation.,"The efficacy of denopamine, an orally active beta 1-adrenoceptor agonist, in improving cardiac failure was assessed in dog heart-lung preparations. Cardiac functions depressed by pentobarbital (118 +/- 28 mg; mean value +/- SD) such that cardiac output and maximum rate of rise of left ventricular pressure (LV dP/dt max) had been reduced by about 35% and 26% of the respective controls were improved by denopamine (10-300 micrograms) in a dose-dependent manner. With 100 micrograms denopamine, almost complete restoration of cardiac performance was attained, associated with a slight increase in heart rate. No arrhythmias were induced by these doses of denopamine. The results warrant clinical trials of denopamine in the treatment of cardiac failure.","[{'text': 'denopamine', 'type': 'Chemical', 'start': 15, 'end': 25, 'mesh': 'C037293'}, {'text': 'TA-064', 'type': 'Chemical', 'start': 27, 'end': 33, 'mesh': 'C037293'}, {'text': 'pentobarbital', 'type': 'Chemical', 'start': 38, 'end': 51, 'mesh': 'D010424'}, {'text': 'cardiac failure', 'type': 'Disease', 'start': 60, 'end': 75, 'mesh': 'D006333'}, {'text': 'denopamine', 'type': 'Chemical', 'start': 127, 'end': 137, 'mesh': 'C037293'}, {'text': 'cardiac failure', 'type': 'Disease', 'start': 198, 'end': 213, 'mesh': 'D006333'}, {'text': 'pentobarbital', 'type': 'Chemical', 'start': 290, 'end': 303, 'mesh': 'D010424'}, {'text': 'denopamine', 'type': 'Chemical', 'start': 515, 'end': 525, 'mesh': 'C037293'}, {'text': 'denopamine', 'type': 'Chemical', 'start': 594, 'end': 604, 'mesh': 'C037293'}, {'text': 'arrhythmias', 'type': 'Disease', 'start': 723, 'end': 734, 'mesh': 'D001145'}, {'text': 'denopamine', 'type': 'Chemical', 'start': 766, 'end': 776, 'mesh': 'C037293'}, {'text': 'denopamine', 'type': 'Chemical', 'start': 817, 'end': 827, 'mesh': 'C037293'}, {'text': 'cardiac failure', 'type': 'Disease', 'start': 848, 'end': 863, 'mesh': 'D006333'}]"
+1221,3832950,Clonazepam monotherapy for epilepsy in childhood.,"Sixty patients (age-range one month to 14 years) with other types of epilepsy than infantile spasms were treated with clonazepam. Disappearance of seizures and normalization of abnormal EEG with disappearance of seizures were recognized in 77% and 50%, respectively. Seizures disappeared in 71% of the patients with generalized seizures and 89% of partial seizures. Improvement of abnormal EEG was noticed in 76% of diffuse paroxysms and in 67% of focal paroxysms. In excellent cases, mean effective dosages were 0.086 +/- 0.021 mg/kg/day in infants and 0.057 +/- 0.022 mg/kg/day in schoolchildren, this difference was statistically significant (p less than 0.005). The incidence of side effects such as drowsiness and ataxia was only 5%.","[{'text': 'Clonazepam', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D002998'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 27, 'end': 35, 'mesh': 'D004827'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 119, 'end': 127, 'mesh': 'D004827'}, {'text': 'infantile spasms', 'type': 'Disease', 'start': 133, 'end': 149, 'mesh': 'D013036'}, {'text': 'clonazepam', 'type': 'Chemical', 'start': 168, 'end': 178, 'mesh': 'D002998'}, {'text': 'seizures', 'type': 'Disease', 'start': 197, 'end': 205, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 262, 'end': 270, 'mesh': 'D012640'}, {'text': 'Seizures', 'type': 'Disease', 'start': 317, 'end': 325, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 378, 'end': 386, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 406, 'end': 414, 'mesh': 'D012640'}, {'text': 'drowsiness', 'type': 'Disease', 'start': 754, 'end': 764, 'mesh': 'D006970'}, {'text': 'ataxia', 'type': 'Disease', 'start': 769, 'end': 775, 'mesh': 'D001259'}]"
+1222,3833372,Postmarketing study of timolol-hydrochlorothiazide antihypertensive therapy.,"A postmarketing surveillance study was conducted to determine the safety and efficacy of a fixed-ratio combination containing 10 mg of timolol maleate and 25 mg of hydrochlorothiazide, administered twice daily for one month to hypertensive patients. Data on 9,037 patients were collected by 1,455 participating physicians. Mean systolic blood pressure decreased 25 mmHg and mean diastolic blood pressure declined 15 mmHg after one month of timolol-hydrochlorothiazide therapy (P less than 0.01, both comparisons). Age, race, and sex appeared to have no influence on the decrease in blood pressure. The antihypertensive effect of the drug was greater in patients with more severe hypertension. Overall, 1,453 patients experienced a total of 2,658 adverse events, the most common being fatigue, dizziness, and weakness. Treatment in 590 patients was discontinued because of adverse events.","[{'text': 'timolol', 'type': 'Chemical', 'start': 23, 'end': 30, 'mesh': 'D013999'}, {'text': 'hydrochlorothiazide', 'type': 'Chemical', 'start': 31, 'end': 50, 'mesh': 'D006852'}, {'text': 'timolol maleate', 'type': 'Chemical', 'start': 212, 'end': 227, 'mesh': 'D013999'}, {'text': 'hydrochlorothiazide', 'type': 'Chemical', 'start': 241, 'end': 260, 'mesh': 'D006852'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 304, 'end': 316, 'mesh': 'D006973'}, {'text': 'timolol', 'type': 'Chemical', 'start': 517, 'end': 524, 'mesh': 'D013999'}, {'text': 'hydrochlorothiazide', 'type': 'Chemical', 'start': 525, 'end': 544, 'mesh': 'D006852'}, {'text': 'hypertension', 'type': 'Disease', 'start': 756, 'end': 768, 'mesh': 'D006973'}, {'text': 'fatigue', 'type': 'Disease', 'start': 861, 'end': 868, 'mesh': 'D005221'}, {'text': 'dizziness', 'type': 'Disease', 'start': 870, 'end': 879, 'mesh': 'D004244'}, {'text': 'weakness', 'type': 'Disease', 'start': 885, 'end': 893, 'mesh': 'D018908'}]"
+1223,3864191,Salicylate nephropathy in the Gunn rat: potential role of prostaglandins.,"We examined the potential role of prostaglandins in the development of analgesic nephropathy in the Gunn strain of rat. The homozygous Gunn rats have unconjugated hyperbilirubinemia due to the absence of glucuronyl transferase, leading to marked bilirubin deposition in renal medulla and papilla. These rats are also highly susceptible to develop papillary necrosis with analgesic administration. We used homozygous (jj) and phenotypically normal heterozygous (jJ) animals. Four groups of rats (n = 7) were studied: jj and jJ rats treated either with aspirin 300 mg/kg every other day or sham-treated. After one week, slices of cortex, outer and inner medulla from one kidney were incubated in buffer and prostaglandin synthesis was determined by radioimmunoassay. The other kidney was examined histologically. A marked corticomedullary gradient of prostaglandin synthesis was observed in all groups. PGE2 synthesis was significantly higher in outer medulla, but not cortex or inner medulla, of jj (38 +/- 6 ng/mg prot) than jJ rats (15 +/- 3) (p less than 0.01). Aspirin treatment reduced PGE2 synthesis in all regions, but outer medullary PGE2 remained higher in jj (18 +/- 3) than jJ rats (9 +/- 2) (p less than 0.05). PGF2 alpha was also significantly higher in the outer medulla of jj rats with and without aspirin administration (p less than 0.05). The changes in renal prostaglandin synthesis were accompanied by evidence of renal damage in aspirin-treated jj but not jJ rats as evidenced by: increased incidence and severity of hematuria (p less than 0.01); increased serum creatinine (p less than 0.05); and increase in outer medullary histopathologic lesions (p less than 0.005 compared to either sham-treated jj or aspirin-treated jJ). These results suggest that enhanced prostaglandin synthesis contributes to maintenance of renal function and morphological integrity, and that inhibition of prostaglandin synthesis may lead to pathological renal medullary lesions and deterioration of renal function.","[{'text': 'Salicylate', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D012459'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 11, 'end': 22, 'mesh': 'D007674'}, {'text': 'prostaglandins', 'type': 'Chemical', 'start': 58, 'end': 72, 'mesh': 'D011453'}, {'text': 'prostaglandins', 'type': 'Chemical', 'start': 108, 'end': 122, 'mesh': 'D011453'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 155, 'end': 166, 'mesh': 'D007674'}, {'text': 'hyperbilirubinemia', 'type': 'Disease', 'start': 237, 'end': 255, 'mesh': 'D006932'}, {'text': 'glucuronyl', 'type': 'Chemical', 'start': 278, 'end': 288, 'mesh': '-1'}, {'text': 'bilirubin', 'type': 'Chemical', 'start': 320, 'end': 329, 'mesh': 'D001663'}, {'text': 'papillary necrosis', 'type': 'Disease', 'start': 421, 'end': 439, 'mesh': 'D007681'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 625, 'end': 632, 'mesh': 'D001241'}, {'text': 'prostaglandin', 'type': 'Chemical', 'start': 779, 'end': 792, 'mesh': 'D011453'}, {'text': 'prostaglandin', 'type': 'Chemical', 'start': 923, 'end': 936, 'mesh': 'D011453'}, {'text': 'PGE2', 'type': 'Chemical', 'start': 975, 'end': 979, 'mesh': 'D015232'}, {'text': 'Aspirin', 'type': 'Chemical', 'start': 1138, 'end': 1145, 'mesh': 'D001241'}, {'text': 'PGE2', 'type': 'Chemical', 'start': 1164, 'end': 1168, 'mesh': 'D015232'}, {'text': 'PGE2', 'type': 'Chemical', 'start': 1215, 'end': 1219, 'mesh': 'D015232'}, {'text': 'PGF2 alpha', 'type': 'Chemical', 'start': 1296, 'end': 1306, 'mesh': 'D015237'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1386, 'end': 1393, 'mesh': 'D001241'}, {'text': 'prostaglandin', 'type': 'Chemical', 'start': 1450, 'end': 1463, 'mesh': 'D011453'}, {'text': 'renal damage', 'type': 'Disease', 'start': 1506, 'end': 1518, 'mesh': 'D007674'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1522, 'end': 1529, 'mesh': 'D001241'}, {'text': 'hematuria', 'type': 'Disease', 'start': 1610, 'end': 1619, 'mesh': 'D006417'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1656, 'end': 1666, 'mesh': 'D003404'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1800, 'end': 1807, 'mesh': 'D001241'}, {'text': 'prostaglandin', 'type': 'Chemical', 'start': 1857, 'end': 1870, 'mesh': 'D011453'}, {'text': 'prostaglandin', 'type': 'Chemical', 'start': 1978, 'end': 1991, 'mesh': 'D011453'}, {'text': 'pathological renal medullary lesions', 'type': 'Disease', 'start': 2014, 'end': 2050, 'mesh': 'D058186'}, {'text': 'deterioration of renal function', 'type': 'Disease', 'start': 2055, 'end': 2086, 'mesh': 'D007674'}]"
+1224,3895875,Prophylactic lidocaine in the early phase of suspected myocardial infarction.,"Four hundred two patients with suspected myocardial infarction seen within 6 hours of the onset of symptoms entered a double-blind randomized trial of lidocaine vs placebo. During the 1 hour after administration of the drug the incidence of ventricular fibrillation or sustained ventricular tachycardia among the 204 patients with acute myocardial infarction was low, 1.5%. Lidocaine, given in a 300 mg dose intramuscularly followed by 100 mg intravenously, did not prevent sustained ventricular tachycardia, although there was a significant reduction in the number of patients with warning arrhythmias between 15 and 45 minutes after the administration of lidocaine (p less than 0.05). The average plasma lidocaine level 10 minutes after administration for patients without a myocardial infarction was significantly higher than that for patients with an acute infarction. The mean plasma lidocaine level of patients on beta-blocking agents was no different from that in patients not on beta blocking agents. During the 1-hour study period, the incidence of central nervous system side effects was significantly greater in the lidocaine group, hypotension occurred in 11 patients, nine of whom had received lidocaine, and four patients died from asystole, three of whom had had lidocaine. We cannot advocate the administration of lidocaine prophylactically in the early hours of suspected myocardial infarction.","[{'text': 'lidocaine', 'type': 'Chemical', 'start': 13, 'end': 22, 'mesh': 'D008012'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 55, 'end': 76, 'mesh': 'D009203'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 119, 'end': 140, 'mesh': 'D009203'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 229, 'end': 238, 'mesh': 'D008012'}, {'text': 'ventricular fibrillation', 'type': 'Disease', 'start': 319, 'end': 343, 'mesh': 'D014693'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 357, 'end': 380, 'mesh': 'D017180'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 415, 'end': 436, 'mesh': 'D009203'}, {'text': 'Lidocaine', 'type': 'Chemical', 'start': 452, 'end': 461, 'mesh': 'D008012'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 562, 'end': 585, 'mesh': 'D017180'}, {'text': 'arrhythmias', 'type': 'Disease', 'start': 669, 'end': 680, 'mesh': 'D001145'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 735, 'end': 744, 'mesh': 'D008012'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 784, 'end': 793, 'mesh': 'D008012'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 855, 'end': 876, 'mesh': 'D009203'}, {'text': 'infarction', 'type': 'Disease', 'start': 939, 'end': 949, 'mesh': 'D007238'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 967, 'end': 976, 'mesh': 'D008012'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 1205, 'end': 1214, 'mesh': 'D008012'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1222, 'end': 1233, 'mesh': 'D007022'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 1285, 'end': 1294, 'mesh': 'D008012'}, {'text': 'asystole', 'type': 'Disease', 'start': 1324, 'end': 1332, 'mesh': 'D006323'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 1356, 'end': 1365, 'mesh': 'D008012'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 1408, 'end': 1417, 'mesh': 'D008012'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 1467, 'end': 1488, 'mesh': 'D009203'}]"
+1225,3925479,Evidence for a cholinergic role in haloperidol-induced catalepsy.,"Experiments in mice tested previous evidence that activation of cholinergic systems promotes catalepsy and that cholinergic mechanisms need to be intact for full expression of neuroleptic-induced catalepsy. Large doses of the cholinomimetic, pilocarpine, could induce catalepsy when peripheral cholinergic receptors were blocked. Low doses of pilocarpine caused a pronounced enhancement of the catalepsy that was induced by the dopaminergic blocker, haloperidol. A muscarinic receptor blocker, atropine, disrupted haloperidol-induced catalepsy. Intracranial injection of an acetylcholine-synthesis inhibitor, hemicholinium, prevented the catalepsy that is usually induced by haloperidol. These findings suggest the hypothesis that the catalepsy that is produced by neuroleptics such as haloperidol is actually mediated by intrinsic central cholinergic systems. Alternatively, activation of central cholinergic systems could promote catalepsy by suppression of dopaminergic systems.","[{'text': 'haloperidol', 'type': 'Chemical', 'start': 35, 'end': 46, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 55, 'end': 64, 'mesh': 'D002375'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 159, 'end': 168, 'mesh': 'D002375'}, {'text': 'neuroleptic', 'type': 'Chemical', 'start': 242, 'end': 253, 'mesh': 'D014150'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 262, 'end': 271, 'mesh': 'D002375'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 308, 'end': 319, 'mesh': 'D010862'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 334, 'end': 343, 'mesh': 'D002375'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 409, 'end': 420, 'mesh': 'D010862'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 460, 'end': 469, 'mesh': 'D002375'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 516, 'end': 527, 'mesh': 'D006220'}, {'text': 'atropine', 'type': 'Chemical', 'start': 560, 'end': 568, 'mesh': 'D001285'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 580, 'end': 591, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 600, 'end': 609, 'mesh': 'D002375'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 640, 'end': 653, 'mesh': 'D000109'}, {'text': 'hemicholinium', 'type': 'Chemical', 'start': 675, 'end': 688, 'mesh': 'D006426'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 704, 'end': 713, 'mesh': 'D002375'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 741, 'end': 752, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 801, 'end': 810, 'mesh': 'D002375'}, {'text': 'neuroleptics', 'type': 'Chemical', 'start': 831, 'end': 843, 'mesh': 'D014150'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 852, 'end': 863, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 998, 'end': 1007, 'mesh': 'D002375'}]"
+1226,3975902,Cardiovascular dysfunction and hypersensitivity to sodium pentobarbital induced by chronic barium chloride ingestion.,"Barium-supplemented Long-Evans hooded rats were characterized by a persistent hypertension that was evident after 1 month of barium (100 micrograms/ml mineral fortified water) treatment. Analysis of in vivo myocardial excitability, contractility, and metabolic characteristics at 16 months revealed other significant barium-induced disturbances within the cardiovascular system. The most distinctive aspect of the barium effect was a demonstrated hypersensitivity of the cardiovascular system to sodium pentobarbital. Under barbiturate anesthesia, virtually all of the myocardial contractile indices were depressed significantly in barium-exposed rats relative to the corresponding control-fed rats. The lack of a similar response to ketamine and xylazine anesthesia revealed that the cardiovascular actions of sodium pentobarbital in barium-treated rats were linked specifically to this anesthetic, and were not representative of a generalized anesthetic response. Other myocardial pathophysiologic and metabolic changes induced by barium were manifest, irrespective of the anesthetic employed. The contractile element shortening velocity of the cardiac muscle fibers was significantly slower in both groups of barium-treated rats relative to the control groups, irrespective of the anesthetic regimen. Similarly, significant disturbances in myocardial energy metabolism were detected in the barium-exposed rats which were consistent with the reduced contractile element shortening velocity. In addition, the excitability of the cardiac conduction system was depressed preferentially in the atrioventricular nodal region of hearts from barium-exposed rats. Overall, the altered cardiac contractility and excitability characteristics, the myocardial metabolic disturbances, and the hypersensitivity of the cardiovascular system to sodium pentobarbital suggest the existence of a heretofore undescribed cardiomyopathic disorder induced by chronic barium exposure. These experimental findings represent the first indication that life-long barium ingestion may have significant adverse effects on the mammalian cardiovascular system.","[{'text': 'Cardiovascular dysfunction', 'type': 'Disease', 'start': 0, 'end': 26, 'mesh': 'D002318'}, {'text': 'hypersensitivity', 'type': 'Disease', 'start': 31, 'end': 47, 'mesh': 'D004342'}, {'text': 'sodium pentobarbital', 'type': 'Chemical', 'start': 51, 'end': 71, 'mesh': 'D010424'}, {'text': 'barium chloride', 'type': 'Chemical', 'start': 91, 'end': 106, 'mesh': 'C024986'}, {'text': 'Barium', 'type': 'Chemical', 'start': 118, 'end': 124, 'mesh': 'D001464'}, {'text': 'hypertension', 'type': 'Disease', 'start': 196, 'end': 208, 'mesh': 'D006973'}, {'text': 'barium', 'type': 'Chemical', 'start': 243, 'end': 249, 'mesh': 'D001464'}, {'text': 'barium', 'type': 'Chemical', 'start': 435, 'end': 441, 'mesh': 'D001464'}, {'text': 'disturbances within the cardiovascular system', 'type': 'Disease', 'start': 450, 'end': 495, 'mesh': 'D002318'}, {'text': 'barium', 'type': 'Chemical', 'start': 532, 'end': 538, 'mesh': 'D001464'}, {'text': 'hypersensitivity', 'type': 'Disease', 'start': 565, 'end': 581, 'mesh': 'D004342'}, {'text': 'sodium pentobarbital', 'type': 'Chemical', 'start': 614, 'end': 634, 'mesh': 'D010424'}, {'text': 'barbiturate', 'type': 'Chemical', 'start': 642, 'end': 653, 'mesh': 'C032232'}, {'text': 'barium', 'type': 'Chemical', 'start': 750, 'end': 756, 'mesh': 'D001464'}, {'text': 'ketamine', 'type': 'Chemical', 'start': 852, 'end': 860, 'mesh': 'D007649'}, {'text': 'xylazine', 'type': 'Chemical', 'start': 865, 'end': 873, 'mesh': 'D014991'}, {'text': 'sodium pentobarbital', 'type': 'Chemical', 'start': 929, 'end': 949, 'mesh': 'D010424'}, {'text': 'barium', 'type': 'Chemical', 'start': 953, 'end': 959, 'mesh': 'D001464'}, {'text': 'barium', 'type': 'Chemical', 'start': 1151, 'end': 1157, 'mesh': 'D001464'}, {'text': 'barium', 'type': 'Chemical', 'start': 1330, 'end': 1336, 'mesh': 'D001464'}, {'text': 'barium', 'type': 'Chemical', 'start': 1511, 'end': 1517, 'mesh': 'D001464'}, {'text': 'barium', 'type': 'Chemical', 'start': 1755, 'end': 1761, 'mesh': 'D001464'}, {'text': 'metabolic disturbances', 'type': 'Disease', 'start': 1868, 'end': 1890, 'mesh': 'D008659'}, {'text': 'hypersensitivity', 'type': 'Disease', 'start': 1900, 'end': 1916, 'mesh': 'D004342'}, {'text': 'sodium pentobarbital', 'type': 'Chemical', 'start': 1949, 'end': 1969, 'mesh': 'D010424'}, {'text': 'cardiomyopathic disorder', 'type': 'Disease', 'start': 2020, 'end': 2044, 'mesh': 'D009202'}, {'text': 'barium', 'type': 'Chemical', 'start': 2064, 'end': 2070, 'mesh': 'D001464'}, {'text': 'barium', 'type': 'Chemical', 'start': 2155, 'end': 2161, 'mesh': 'D001464'}]"
+1227,3987172,Propranolol antagonism of phenylpropanolamine-induced hypertension.,"Phenylpropanolamine (PPA) overdose can cause severe hypertension, intracerebral hemorrhage, and death. We studied the efficacy and safety of propranolol in the treatment of PPA-induced hypertension. Subjects received propranolol either by mouth for 48 hours before PPA or as a rapid intravenous infusion after PPA. PPA, 75 mg alone, increased blood pressure (31 +/- 14 mm Hg systolic, 20 +/- 5 mm Hg diastolic), and propranolol pretreatment antagonized this increase (12 +/- 10 mm Hg systolic, 10 +/- 7 mm Hg diastolic). Intravenous propranolol after PPA also decreased blood pressure. Left ventricular function (assessed by echocardiography) showed that PPA increased the stroke volume 30% (from 62.5 +/- 20.9 to 80.8 +/- 22.4 ml), the ejection fraction 9% (from 64% +/- 10% to 70% +/- 7%), and cardiac output 14% (from 3.6 +/- 0.6 to 4.1 +/- 1.0 L/min). Intravenous propranolol reversed these effects. Systemic vascular resistance was increased by PPA 28% (from 1710 +/- 200 to 2190 +/- 700 dyne X sec/cm5) and was further increased by propranolol 22% (to 2660 +/- 1200 dyne X sec/cm5). We conclude that PPA increases blood pressure by increasing systemic vascular resistance and cardiac output, and that propranolol antagonizes this increase by reversing the effect of PPA on cardiac output. That propranolol antagonizes the pressor effect of PPA is in contrast to the interaction in which propranolol enhances the pressor effect of norepinephrine. This is probably because PPA has less beta 2 activity than does norepinephrine.","[{'text': 'Propranolol', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D011433'}, {'text': 'phenylpropanolamine', 'type': 'Chemical', 'start': 26, 'end': 45, 'mesh': 'D010665'}, {'text': 'hypertension', 'type': 'Disease', 'start': 54, 'end': 66, 'mesh': 'D006973'}, {'text': 'Phenylpropanolamine', 'type': 'Chemical', 'start': 68, 'end': 87, 'mesh': 'D010665'}, {'text': 'PPA', 'type': 'Chemical', 'start': 89, 'end': 92, 'mesh': 'D010665'}, {'text': 'overdose', 'type': 'Disease', 'start': 94, 'end': 102, 'mesh': 'D062787'}, {'text': 'hypertension', 'type': 'Disease', 'start': 120, 'end': 132, 'mesh': 'D006973'}, {'text': 'intracerebral hemorrhage', 'type': 'Disease', 'start': 134, 'end': 158, 'mesh': 'D002543'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 209, 'end': 220, 'mesh': 'D011433'}, {'text': 'PPA', 'type': 'Chemical', 'start': 241, 'end': 244, 'mesh': 'D010665'}, {'text': 'hypertension', 'type': 'Disease', 'start': 253, 'end': 265, 'mesh': 'D006973'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 285, 'end': 296, 'mesh': 'D011433'}, {'text': 'PPA', 'type': 'Chemical', 'start': 333, 'end': 336, 'mesh': 'D010665'}, {'text': 'PPA', 'type': 'Chemical', 'start': 378, 'end': 381, 'mesh': 'D010665'}, {'text': 'PPA', 'type': 'Chemical', 'start': 383, 'end': 386, 'mesh': 'D010665'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 484, 'end': 495, 'mesh': 'D011433'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 601, 'end': 612, 'mesh': 'D011433'}, {'text': 'PPA', 'type': 'Chemical', 'start': 619, 'end': 622, 'mesh': 'D010665'}, {'text': 'PPA', 'type': 'Chemical', 'start': 723, 'end': 726, 'mesh': 'D010665'}, {'text': 'stroke', 'type': 'Disease', 'start': 741, 'end': 747, 'mesh': 'D020521'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 936, 'end': 947, 'mesh': 'D011433'}, {'text': 'PPA', 'type': 'Chemical', 'start': 1018, 'end': 1021, 'mesh': 'D010665'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 1106, 'end': 1117, 'mesh': 'D011433'}, {'text': 'PPA', 'type': 'Chemical', 'start': 1174, 'end': 1177, 'mesh': 'D010665'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 1275, 'end': 1286, 'mesh': 'D011433'}, {'text': 'PPA', 'type': 'Chemical', 'start': 1340, 'end': 1343, 'mesh': 'D010665'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 1368, 'end': 1379, 'mesh': 'D011433'}, {'text': 'PPA', 'type': 'Chemical', 'start': 1414, 'end': 1417, 'mesh': 'D010665'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 1461, 'end': 1472, 'mesh': 'D011433'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 1504, 'end': 1518, 'mesh': 'D009638'}, {'text': 'PPA', 'type': 'Chemical', 'start': 1545, 'end': 1548, 'mesh': 'D010665'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 1584, 'end': 1598, 'mesh': 'D009638'}]"
+1228,3990093,Mesangial function and glomerular sclerosis in rats with aminonucleoside nephrosis.,"The possible relationship between mesangial dysfunction and development of glomerular sclerosis was studied in the puromycin aminonucleoside (PAN) model. Five male Wistar rats received repeated subcutaneous PAN injections; five controls received saline only. After 4 weeks the PAN rats were severely proteinuric (190 +/- 80 mg/24 hr), and all rats were given colloidal carbon (CC) intravenously. At 5 months glomerular sclerosis was found in 7.6 +/- 3.4% of the glomeruli of PAN rats; glomeruli of the controls were normal. Glomeruli of PAN rats contained significantly more CC than glomeruli of controls. Glomeruli with sclerosis contained significantly more CC than non-sclerotic glomeruli in the same kidneys. CC was preferentially localized within the sclerotic areas of the affected glomeruli. Since mesangial CC clearance from the mesangium did not change during chronic PAN treatment, we conclude that this preferential CC localization within the lesions is caused by an increased CC uptake shortly after injection in apparent vulnerable areas where sclerosis will develop subsequently. Cluster analysis showed a random distribution of lesions in the PAN glomeruli in concordance with the random localization of mesangial areas with dysfunction in this model. Similar to the remnant kidney model in PAN nephrosis the development of glomerular sclerosis may be related to ""mesangial overloading.""","[{'text': 'glomerular sclerosis', 'type': 'Disease', 'start': 23, 'end': 43, 'mesh': 'D007674'}, {'text': 'aminonucleoside', 'type': 'Chemical', 'start': 57, 'end': 72, 'mesh': 'D011692'}, {'text': 'nephrosis', 'type': 'Disease', 'start': 73, 'end': 82, 'mesh': 'D009401'}, {'text': 'mesangial dysfunction', 'type': 'Disease', 'start': 118, 'end': 139, 'mesh': 'D007674'}, {'text': 'glomerular sclerosis', 'type': 'Disease', 'start': 159, 'end': 179, 'mesh': 'D007674'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 199, 'end': 224, 'mesh': 'D011692'}, {'text': 'PAN', 'type': 'Chemical', 'start': 226, 'end': 229, 'mesh': 'D011692'}, {'text': 'PAN', 'type': 'Chemical', 'start': 291, 'end': 294, 'mesh': 'D011692'}, {'text': 'PAN', 'type': 'Chemical', 'start': 361, 'end': 364, 'mesh': 'D011692'}, {'text': 'proteinuric', 'type': 'Disease', 'start': 384, 'end': 395, 'mesh': 'D011507'}, {'text': 'carbon', 'type': 'Chemical', 'start': 453, 'end': 459, 'mesh': 'D002244'}, {'text': 'glomerular sclerosis', 'type': 'Disease', 'start': 492, 'end': 512, 'mesh': 'D007674'}, {'text': 'PAN', 'type': 'Chemical', 'start': 559, 'end': 562, 'mesh': 'D011692'}, {'text': 'PAN', 'type': 'Chemical', 'start': 621, 'end': 624, 'mesh': 'D011692'}, {'text': 'sclerosis', 'type': 'Disease', 'start': 705, 'end': 714, 'mesh': 'D012598'}, {'text': 'PAN', 'type': 'Chemical', 'start': 961, 'end': 964, 'mesh': 'D011692'}, {'text': 'sclerosis', 'type': 'Disease', 'start': 1141, 'end': 1150, 'mesh': 'D012598'}, {'text': 'PAN', 'type': 'Chemical', 'start': 1242, 'end': 1245, 'mesh': 'D011692'}, {'text': 'PAN', 'type': 'Chemical', 'start': 1390, 'end': 1393, 'mesh': 'D011692'}, {'text': 'nephrosis', 'type': 'Disease', 'start': 1394, 'end': 1403, 'mesh': 'D009401'}, {'text': 'glomerular sclerosis', 'type': 'Disease', 'start': 1423, 'end': 1443, 'mesh': 'D007674'}]"
+1229,4010471,Relationship between nicotine-induced seizures and hippocampal nicotinic receptors.,"A controversy has existed for several years concerning the physiological relevance of the nicotinic receptor measured by alpha-bungarotoxin binding. Using mice derived from a classical F2 and backcross genetic design, a relationship between nicotine-induced seizures and alpha-bungarotoxin nicotinic receptor concentration was found. Mice sensitive to the convulsant effects of nicotine had greater alpha-bungarotoxin binding in the hippocampus than seizure insensitive mice. The binding sites from seizure sensitive and resistant mice were equally affected by treatment with dithiothreitol, trypsin or heat. Thus it appears that the difference between seizure sensitive and insensitive animals may be due to a difference in hippocampal nicotinic receptor concentration as measured with alpha-bungarotoxin binding.","[{'text': 'nicotine', 'type': 'Chemical', 'start': 21, 'end': 29, 'mesh': 'D009538'}, {'text': 'seizures', 'type': 'Disease', 'start': 38, 'end': 46, 'mesh': 'D012640'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 325, 'end': 333, 'mesh': 'D009538'}, {'text': 'seizures', 'type': 'Disease', 'start': 342, 'end': 350, 'mesh': 'D012640'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 462, 'end': 470, 'mesh': 'D009538'}, {'text': 'seizure', 'type': 'Disease', 'start': 534, 'end': 541, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 583, 'end': 590, 'mesh': 'D012640'}, {'text': 'dithiothreitol', 'type': 'Chemical', 'start': 660, 'end': 674, 'mesh': 'D004229'}, {'text': 'seizure', 'type': 'Disease', 'start': 737, 'end': 744, 'mesh': 'D012640'}]"
+1230,4082192,The role of p-aminophenol in acetaminophen-induced nephrotoxicity: effect of bis(p-nitrophenyl) phosphate on acetaminophen and p-aminophenol nephrotoxicity and metabolism in Fischer 344 rats.,"Acetaminophen (APAP) produces proximal tubular necrosis in Fischer 344 (F344) rats. Recently, p-aminophenol (PAP), a known potent nephrotoxicant, was identified as a metabolite of APAP in F344 rats. The purpose of this study was to determine if PAP formation is a requisite step in APAP-induced nephrotoxicity. Therefore, the effect of bis(p-nitrophenyl) phosphate (BNPP), an acylamidase inhibitor, on APAP and PAP nephrotoxicity and metabolism was determined. BNPP (1 to 8 mM) reduced APAP deacetylation and covalent binding in F344 renal cortical homogenates in a concentration-dependent manner. Pretreatment of animals with BNPP prior to APAP or PAP administration resulted in marked reduction of APAP (900 mg/kg) nephrotoxicity but not PAP nephrotoxicity. This result was not due to altered disposition of either APAP or acetylated metabolites in plasma or renal cortical and hepatic tissue. Rather, BNPP pretreatment reduced the fraction of APAP excreted as PAP by 64 and 75% after APAP doses of 750 and 900 mg/kg. BNPP did not alter the excretion of APAP or any of its non-deacetylated metabolites nor did BNPP alter excretion of PAP or its metabolites after PAP doses of 150 and 300 mg/kg. Therefore, the BNPP-induced reduction in APAP-induced nephrotoxicity appears to be due to inhibition of APAP deacetylation. It is concluded that PAP formation, in vivo, accounts, at least in part, for APAP-induced renal tubular necrosis.","[{'text': 'p-aminophenol', 'type': 'Chemical', 'start': 12, 'end': 25, 'mesh': 'C026729'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 29, 'end': 42, 'mesh': 'D000082'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 51, 'end': 65, 'mesh': 'D007674'}, {'text': 'bis(p-nitrophenyl) phosphate', 'type': 'Chemical', 'start': 77, 'end': 105, 'mesh': 'C002887'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 109, 'end': 122, 'mesh': 'D000082'}, {'text': 'p-aminophenol', 'type': 'Chemical', 'start': 127, 'end': 140, 'mesh': 'C026729'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 141, 'end': 155, 'mesh': 'D007674'}, {'text': 'Acetaminophen', 'type': 'Chemical', 'start': 192, 'end': 205, 'mesh': 'D000082'}, {'text': 'APAP', 'type': 'Chemical', 'start': 207, 'end': 211, 'mesh': 'D000082'}, {'text': 'tubular necrosis', 'type': 'Disease', 'start': 231, 'end': 247, 'mesh': 'D007683'}, {'text': 'p-aminophenol', 'type': 'Chemical', 'start': 286, 'end': 299, 'mesh': 'C026729'}, {'text': 'PAP', 'type': 'Chemical', 'start': 301, 'end': 304, 'mesh': 'C026729'}, {'text': 'APAP', 'type': 'Chemical', 'start': 372, 'end': 376, 'mesh': 'D000082'}, {'text': 'PAP', 'type': 'Chemical', 'start': 437, 'end': 440, 'mesh': 'C026729'}, {'text': 'APAP', 'type': 'Chemical', 'start': 474, 'end': 478, 'mesh': 'D000082'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 487, 'end': 501, 'mesh': 'D007674'}, {'text': 'bis(p-nitrophenyl) phosphate', 'type': 'Chemical', 'start': 528, 'end': 556, 'mesh': 'C002887'}, {'text': 'BNPP', 'type': 'Chemical', 'start': 558, 'end': 562, 'mesh': 'C002887'}, {'text': 'APAP', 'type': 'Chemical', 'start': 594, 'end': 598, 'mesh': 'D000082'}, {'text': 'PAP', 'type': 'Chemical', 'start': 603, 'end': 606, 'mesh': 'C026729'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 607, 'end': 621, 'mesh': 'D007674'}, {'text': 'BNPP', 'type': 'Chemical', 'start': 653, 'end': 657, 'mesh': 'C002887'}, {'text': 'APAP', 'type': 'Chemical', 'start': 678, 'end': 682, 'mesh': 'D000082'}, {'text': 'BNPP', 'type': 'Chemical', 'start': 819, 'end': 823, 'mesh': 'C002887'}, {'text': 'APAP', 'type': 'Chemical', 'start': 833, 'end': 837, 'mesh': 'D000082'}, {'text': 'PAP', 'type': 'Chemical', 'start': 841, 'end': 844, 'mesh': 'C026729'}, {'text': 'APAP', 'type': 'Chemical', 'start': 892, 'end': 896, 'mesh': 'D000082'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 909, 'end': 923, 'mesh': 'D007674'}, {'text': 'PAP', 'type': 'Chemical', 'start': 932, 'end': 935, 'mesh': 'C026729'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 936, 'end': 950, 'mesh': 'D007674'}, {'text': 'APAP', 'type': 'Chemical', 'start': 1009, 'end': 1013, 'mesh': 'D000082'}, {'text': 'BNPP', 'type': 'Chemical', 'start': 1096, 'end': 1100, 'mesh': 'C002887'}, {'text': 'APAP', 'type': 'Chemical', 'start': 1138, 'end': 1142, 'mesh': 'D000082'}, {'text': 'PAP', 'type': 'Chemical', 'start': 1155, 'end': 1158, 'mesh': 'C026729'}, {'text': 'APAP', 'type': 'Chemical', 'start': 1179, 'end': 1183, 'mesh': 'D000082'}, {'text': 'BNPP', 'type': 'Chemical', 'start': 1212, 'end': 1216, 'mesh': 'C002887'}, {'text': 'APAP', 'type': 'Chemical', 'start': 1248, 'end': 1252, 'mesh': 'D000082'}, {'text': 'BNPP', 'type': 'Chemical', 'start': 1304, 'end': 1308, 'mesh': 'C002887'}, {'text': 'PAP', 'type': 'Chemical', 'start': 1328, 'end': 1331, 'mesh': 'C026729'}, {'text': 'PAP', 'type': 'Chemical', 'start': 1357, 'end': 1360, 'mesh': 'C026729'}, {'text': 'BNPP', 'type': 'Chemical', 'start': 1404, 'end': 1408, 'mesh': 'C002887'}, {'text': 'APAP', 'type': 'Chemical', 'start': 1430, 'end': 1434, 'mesh': 'D000082'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1443, 'end': 1457, 'mesh': 'D007674'}, {'text': 'APAP', 'type': 'Chemical', 'start': 1493, 'end': 1497, 'mesh': 'D000082'}, {'text': 'PAP', 'type': 'Chemical', 'start': 1534, 'end': 1537, 'mesh': 'C026729'}, {'text': 'APAP', 'type': 'Chemical', 'start': 1590, 'end': 1594, 'mesh': 'D000082'}, {'text': 'renal tubular necrosis', 'type': 'Disease', 'start': 1603, 'end': 1625, 'mesh': 'D007683'}]"
+1231,4082466,Morphine-induced seizures in newborn infants.,Two neonates suffered from generalized seizures during the course of intravenous morphine sulfate for post-operative analgesia. They received morphine in doses of 32 micrograms/kg/hr and 40 micrograms/kg/hr larger than a group of 10 neonates who received 6-24 micrograms/kg/hr and had no seizures. Plasma concentrations of morphine in these neonates was excessive (60 and 90 mg/ml). Other known reasons for seizures were ruled out and the convulsions stopped a few hours after cessation of morphine and did not reoccur in the subsequent 8 months. It is suggested that post-operative intravenous morphine should not exceed 20 micrograms/kg/ml in neonates.,"[{'text': 'Morphine', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D009020'}, {'text': 'seizures', 'type': 'Disease', 'start': 17, 'end': 25, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 85, 'end': 93, 'mesh': 'D012640'}, {'text': 'morphine sulfate', 'type': 'Chemical', 'start': 127, 'end': 143, 'mesh': 'D009020'}, {'text': 'morphine', 'type': 'Chemical', 'start': 188, 'end': 196, 'mesh': 'D009020'}, {'text': 'seizures', 'type': 'Disease', 'start': 334, 'end': 342, 'mesh': 'D012640'}, {'text': 'morphine', 'type': 'Chemical', 'start': 369, 'end': 377, 'mesh': 'D009020'}, {'text': 'seizures', 'type': 'Disease', 'start': 453, 'end': 461, 'mesh': 'D012640'}, {'text': 'convulsions', 'type': 'Disease', 'start': 485, 'end': 496, 'mesh': 'D012640'}, {'text': 'morphine', 'type': 'Chemical', 'start': 536, 'end': 544, 'mesh': 'D009020'}, {'text': 'morphine', 'type': 'Chemical', 'start': 641, 'end': 649, 'mesh': 'D009020'}]"
+1232,4631913,Effect of vincristine sulfate on Pseudomonas infections in monkeys.,"In rhesus monkeys, intravenous challenge with 0.6 x 10(10) to 2.2 x 10(10)Pseudomonas aeruginosa organisms caused acute illness of 4 to 5 days' duration with spontaneous recovery in 13 of 15 monkeys; blood cultures became negative 3 to 17 days after challenge. Leukocytosis was observed in all monkeys. Intravenous or intratracheal inoculation of 2.0 to 2.5 mg of vincristine sulfate was followed by leukopenia in 4 to 5 days. Intravenous inoculation of 4.2 x 10(10) to 7.8 x 10(10) pyocin type 6 Pseudomonas organisms in monkeys given vincristine sulfate 4 days previously resulted in fatal infection in 11 of 14 monkeys, whereas none of four receiving Pseudomonas alone died. These studies suggest that an antimetabolite-induced leukopenia predisposes to severe Pseudomonas sepsis and that such monkeys may serve as a biological model for study of comparative efficacy of antimicrobial agents.","[{'text': 'vincristine sulfate', 'type': 'Chemical', 'start': 10, 'end': 29, 'mesh': 'D014750'}, {'text': 'Pseudomonas infections', 'type': 'Disease', 'start': 33, 'end': 55, 'mesh': 'D011552'}, {'text': 'Leukocytosis', 'type': 'Disease', 'start': 329, 'end': 341, 'mesh': 'D007964'}, {'text': 'vincristine sulfate', 'type': 'Chemical', 'start': 432, 'end': 451, 'mesh': 'D014750'}, {'text': 'leukopenia', 'type': 'Disease', 'start': 468, 'end': 478, 'mesh': 'D007970'}, {'text': 'vincristine sulfate', 'type': 'Chemical', 'start': 604, 'end': 623, 'mesh': 'D014750'}, {'text': 'infection', 'type': 'Disease', 'start': 660, 'end': 669, 'mesh': 'D007239'}, {'text': 'leukopenia', 'type': 'Disease', 'start': 799, 'end': 809, 'mesh': 'D007970'}, {'text': 'sepsis', 'type': 'Disease', 'start': 844, 'end': 850, 'mesh': 'D018805'}]"
+1233,6106951,Central excitatory actions of flurazepam.,"Toxic actions of flurazepam (FZP) were studied in cats, mice and rats. High doses caused an apparent central excitation, most clearly seen as clonic convulsions, superimposed on general depression. Following a lethal dose, death was always associated with convulsions. Comparing the relative sensitivity to central depression and excitation revealed that rats were least likely to have convulsions at doses that did not first cause loss of consciousness, while cats most clearly showed marked central excitatory actions. Signs of FZP toxocity in cats included excessive salivation, extreme apprehensive behavior, retching, muscle tremors and convulsions. An interaction between FZP and pentylenetetrazol (PTZ) was shown by pretreating mice with FZP before PTZ challenge. As a function of dose, FZP first protected against convulsions and death. At higher doses, however, convulsions again emerged. These doses of FZP were lower than those that would alone cause convulsions. These results may be relevant to the use of FZP in clinical situations in which there is increased neural excitability, such as epilepsy or sedative-hypnotic drug withdrawal.","[{'text': 'flurazepam', 'type': 'Chemical', 'start': 30, 'end': 40, 'mesh': 'D005479'}, {'text': 'flurazepam', 'type': 'Chemical', 'start': 59, 'end': 69, 'mesh': 'D005479'}, {'text': 'FZP', 'type': 'Chemical', 'start': 71, 'end': 74, 'mesh': 'D005479'}, {'text': 'convulsions', 'type': 'Disease', 'start': 191, 'end': 202, 'mesh': 'D012640'}, {'text': 'depression', 'type': 'Disease', 'start': 228, 'end': 238, 'mesh': 'D003866'}, {'text': 'convulsions', 'type': 'Disease', 'start': 298, 'end': 309, 'mesh': 'D012640'}, {'text': 'depression', 'type': 'Disease', 'start': 357, 'end': 367, 'mesh': 'D003866'}, {'text': 'convulsions', 'type': 'Disease', 'start': 428, 'end': 439, 'mesh': 'D012640'}, {'text': 'loss of consciousness', 'type': 'Disease', 'start': 474, 'end': 495, 'mesh': 'D014474'}, {'text': 'FZP', 'type': 'Chemical', 'start': 572, 'end': 575, 'mesh': 'D005479'}, {'text': 'toxocity', 'type': 'Disease', 'start': 576, 'end': 584, 'mesh': 'D064420'}, {'text': 'salivation', 'type': 'Disease', 'start': 612, 'end': 622, 'mesh': 'D012798'}, {'text': 'muscle tremors', 'type': 'Disease', 'start': 665, 'end': 679, 'mesh': 'D014202'}, {'text': 'convulsions', 'type': 'Disease', 'start': 684, 'end': 695, 'mesh': 'D012640'}, {'text': 'FZP', 'type': 'Chemical', 'start': 720, 'end': 723, 'mesh': 'D005479'}, {'text': 'pentylenetetrazol', 'type': 'Chemical', 'start': 728, 'end': 745, 'mesh': 'D010433'}, {'text': 'PTZ', 'type': 'Chemical', 'start': 747, 'end': 750, 'mesh': 'D010433'}, {'text': 'FZP', 'type': 'Chemical', 'start': 787, 'end': 790, 'mesh': 'D005479'}, {'text': 'PTZ', 'type': 'Chemical', 'start': 798, 'end': 801, 'mesh': 'D010433'}, {'text': 'FZP', 'type': 'Chemical', 'start': 836, 'end': 839, 'mesh': 'D005479'}, {'text': 'convulsions', 'type': 'Disease', 'start': 864, 'end': 875, 'mesh': 'D012640'}, {'text': 'convulsions', 'type': 'Disease', 'start': 913, 'end': 924, 'mesh': 'D012640'}, {'text': 'FZP', 'type': 'Chemical', 'start': 955, 'end': 958, 'mesh': 'D005479'}, {'text': 'convulsions', 'type': 'Disease', 'start': 1004, 'end': 1015, 'mesh': 'D012640'}, {'text': 'FZP', 'type': 'Chemical', 'start': 1061, 'end': 1064, 'mesh': 'D005479'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 1145, 'end': 1153, 'mesh': 'D004827'}]"
+1234,6299641,Evidence for cardiac beta 2-adrenoceptors in man.,"We compared the effects of single doses of 50 mg atenolol (cardioselective), 40 mg propranolol (nonselective), and placebo on both exercise- and isoproterenol-induced tachycardia in two experiments involving nine normal subjects. Maximal exercise heart rate was reduced from 187 +/- 4(SEM) after placebo to 146 +/- 7 bpm after atenolol and 138 +/- 6 bpm after propranolol, but there were no differences between the drugs. The effects on isoproterenol tachycardia were determined before and after atropine (0.04 mg/kg IV). Isoproterenol sensitivity was determined as the intravenous dose that increased heart rate by 25 bpm (CD25) and this was increased from 1.8 +/- 0.3 micrograms after placebo to 38.9 +/- 8.3 micrograms after propranolol and 8.3 +/- 1.7 micrograms after atenolol. The difference in the effects of the two was significant. After atropine the CD25 was unchanged after placebo (2.3 +/- 0.3 micrograms) and atenolol (7.7 +/- 1.3 micrograms); it was reduced after propranolol (24.8 +/- 5.0 micrograms), but remained different from atenolol. This change with propranolol sensitivity was calculated as the apparent Ka, this was unchanged by atropine (11.7 +/- 2.1 and 10.1 +/- 2.5 ml/ng). These data are consistent with the hypothesis that exercise-induced tachycardia results largely from beta 1-receptor activation that is blocked by both cardioselective and nonselective drugs, whereas isoproterenol activates both beta 1- and beta 2-receptors so that after cardioselective blockade there remains a beta 2-component that can be blocked with a nonselective drug. While there appear to be beta 2-receptors in the human heart, their physiologic or pathologic roles remain to be defined.","[{'text': 'atenolol', 'type': 'Chemical', 'start': 99, 'end': 107, 'mesh': 'D001262'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 133, 'end': 144, 'mesh': 'D011433'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 195, 'end': 208, 'mesh': 'D007545'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 217, 'end': 228, 'mesh': 'D013610'}, {'text': 'atenolol', 'type': 'Chemical', 'start': 377, 'end': 385, 'mesh': 'D001262'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 410, 'end': 421, 'mesh': 'D011433'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 487, 'end': 500, 'mesh': 'D007545'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 501, 'end': 512, 'mesh': 'D013610'}, {'text': 'atropine', 'type': 'Chemical', 'start': 546, 'end': 554, 'mesh': 'D001285'}, {'text': 'Isoproterenol', 'type': 'Chemical', 'start': 572, 'end': 585, 'mesh': 'D007545'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 778, 'end': 789, 'mesh': 'D011433'}, {'text': 'atenolol', 'type': 'Chemical', 'start': 823, 'end': 831, 'mesh': 'D001262'}, {'text': 'atropine', 'type': 'Chemical', 'start': 897, 'end': 905, 'mesh': 'D001285'}, {'text': 'atenolol', 'type': 'Chemical', 'start': 972, 'end': 980, 'mesh': 'D001262'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 1028, 'end': 1039, 'mesh': 'D011433'}, {'text': 'atenolol', 'type': 'Chemical', 'start': 1095, 'end': 1103, 'mesh': 'D001262'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 1122, 'end': 1133, 'mesh': 'D011433'}, {'text': 'atropine', 'type': 'Chemical', 'start': 1203, 'end': 1211, 'mesh': 'D001285'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 1319, 'end': 1330, 'mesh': 'D013610'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1451, 'end': 1464, 'mesh': 'D007545'}]"
+1235,6305660,Hormones and risk of breast cancer.,"This paper reports the results of a study of 50 menopausal women receiving hormonal replacement therapy. The majority (29) had surgical menopause; their mean age was 45.7 years. It was hypothesized that progestins could equilibrate the effects of the estrogenic stimulation on the mammary and endometrial target tissues of women on hormonal replacement therapy. The treatment schedule consisted of conjugated estrogens (Premarin) 1.25 mg/day for 21 days and Medroxyprogesterone acetate 10 mg/day for 10 days in each month. The mean treatment period was 18 months. During the follow-up period, attention was paid to breast modifications as evidenced by symptomatology, physical examination, and plate thermography. Mastodynia was reported by 21 patients, and physical examination revealed a light increase in breast firmness in 12 women and a moderate increase in breast nodularity in 2 women. Themography confirmed the existence of an excessive breast stimulation in 1 women who complained of moderate mastodynia and in 5 of the 7 women who complained of severe mastodynia. Normalization was obtained by halving the estrogen dose. These results suggest that hormonal replacement therapy can be safely prescribed if the following criteria are satisfied: 1) preliminary evaluation of patients from a clinical, metabolic, cytologic, and mammographic perspective; 2) cyclic treatment schedule, with a progestative phase of 10 days; and 3) periodic complete follow-up, with accurate thermographic evaluation of the breast target tissues.","[{'text': 'breast cancer', 'type': 'Disease', 'start': 21, 'end': 34, 'mesh': 'D001943'}, {'text': 'progestins', 'type': 'Chemical', 'start': 239, 'end': 249, 'mesh': 'D011372'}, {'text': 'conjugated estrogens', 'type': 'Chemical', 'start': 434, 'end': 454, 'mesh': 'D004966'}, {'text': 'Premarin', 'type': 'Chemical', 'start': 456, 'end': 464, 'mesh': 'D004966'}, {'text': 'Medroxyprogesterone acetate', 'type': 'Chemical', 'start': 494, 'end': 521, 'mesh': 'D017258'}, {'text': 'Mastodynia', 'type': 'Disease', 'start': 750, 'end': 760, 'mesh': 'D059373'}, {'text': 'mastodynia', 'type': 'Disease', 'start': 1038, 'end': 1048, 'mesh': 'D059373'}, {'text': 'mastodynia', 'type': 'Disease', 'start': 1098, 'end': 1108, 'mesh': 'D059373'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 1152, 'end': 1160, 'mesh': 'D004967'}]"
+1236,6310832,"Early infections in kidney, heart, and liver transplant recipients on cyclosporine.","Eighty-one renal, seventeen heart, and twenty-four liver transplant patients were followed for infection. Seventeen renal patients received azathioprine (Aza) and prednisone as part of a randomized trial of immunosuppression with 21 cyclosporine-and-prednisone-treated renal transplant patients. All others received cyclosporine and prednisone. The randomized Aza patients had more overall infections (P less than 0.05) and more nonviral infections (P less than 0.02) than the randomized cyclosporine patients. Heart and liver patients had more infections than cyclosporine renal patients but fewer infections than the Aza renal patients. There were no infectious deaths in renal transplant patients on cyclosporine or Aza, but infection played a major role in 3 out of 6 cardiac transplant deaths and in 8 out of 9 liver transplant deaths. Renal patients on cyclosporine had the fewest bacteremias. Analysis of site of infection showed a preponderance of abdominal infections in liver patients, intrathoracic infections in heart patients, and urinary tract infections in renal patients. Pulmonary infections were less common in cyclosporine-treated renal patients than in Aza-treated patients (P less than 0.05). Aza patients had significantly more staphylococcal infections than all other transplant groups (P less than 0.005), and systemic fungal infections occurred only in the liver transplant group. Cytomegalovirus (CMV) shedding or serological rises in antibody titer, or both occurred in 78% of cyclosporine patients and 76% of Aza patients. Of the cyclosporine patients, 15% had symptoms related to CMV infection. Serological evidence for Epstein Barr Virus infection was found in 20% of 65 cyclosporine patients studied. Three had associated symptoms, and one developed a lymphoma.","[{'text': 'infections', 'type': 'Disease', 'start': 6, 'end': 16, 'mesh': 'D007239'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 70, 'end': 82, 'mesh': 'D016572'}, {'text': 'infection', 'type': 'Disease', 'start': 179, 'end': 188, 'mesh': 'D007239'}, {'text': 'azathioprine', 'type': 'Chemical', 'start': 224, 'end': 236, 'mesh': 'D001379'}, {'text': 'Aza', 'type': 'Chemical', 'start': 238, 'end': 241, 'mesh': 'D001379'}, {'text': 'prednisone', 'type': 'Chemical', 'start': 247, 'end': 257, 'mesh': 'D011241'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 317, 'end': 329, 'mesh': 'D016572'}, {'text': 'prednisone', 'type': 'Chemical', 'start': 334, 'end': 344, 'mesh': 'D011241'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 400, 'end': 412, 'mesh': 'D016572'}, {'text': 'prednisone', 'type': 'Chemical', 'start': 417, 'end': 427, 'mesh': 'D011241'}, {'text': 'Aza', 'type': 'Chemical', 'start': 444, 'end': 447, 'mesh': 'D001379'}, {'text': 'infections', 'type': 'Disease', 'start': 474, 'end': 484, 'mesh': 'D007239'}, {'text': 'infections', 'type': 'Disease', 'start': 522, 'end': 532, 'mesh': 'D007239'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 572, 'end': 584, 'mesh': 'D016572'}, {'text': 'infections', 'type': 'Disease', 'start': 629, 'end': 639, 'mesh': 'D007239'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 645, 'end': 657, 'mesh': 'D016572'}, {'text': 'infections', 'type': 'Disease', 'start': 683, 'end': 693, 'mesh': 'D007239'}, {'text': 'Aza', 'type': 'Chemical', 'start': 703, 'end': 706, 'mesh': 'D001379'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 787, 'end': 799, 'mesh': 'D016572'}, {'text': 'Aza', 'type': 'Chemical', 'start': 803, 'end': 806, 'mesh': 'D001379'}, {'text': 'infection', 'type': 'Disease', 'start': 812, 'end': 821, 'mesh': 'D007239'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 943, 'end': 955, 'mesh': 'D016572'}, {'text': 'bacteremias', 'type': 'Disease', 'start': 971, 'end': 982, 'mesh': 'D016470'}, {'text': 'infection', 'type': 'Disease', 'start': 1004, 'end': 1013, 'mesh': 'D007239'}, {'text': 'abdominal infections', 'type': 'Disease', 'start': 1040, 'end': 1060, 'mesh': 'D059413'}, {'text': 'infections', 'type': 'Disease', 'start': 1094, 'end': 1104, 'mesh': 'D007239'}, {'text': 'urinary tract infections', 'type': 'Disease', 'start': 1128, 'end': 1152, 'mesh': 'D014552'}, {'text': 'infections', 'type': 'Disease', 'start': 1182, 'end': 1192, 'mesh': 'D007239'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 1213, 'end': 1225, 'mesh': 'D016572'}, {'text': 'Aza', 'type': 'Chemical', 'start': 1257, 'end': 1260, 'mesh': 'D001379'}, {'text': 'Aza', 'type': 'Chemical', 'start': 1298, 'end': 1301, 'mesh': 'D001379'}, {'text': 'staphylococcal infections', 'type': 'Disease', 'start': 1334, 'end': 1359, 'mesh': 'D013203'}, {'text': 'fungal infections', 'type': 'Disease', 'start': 1427, 'end': 1444, 'mesh': 'D009181'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 1588, 'end': 1600, 'mesh': 'D016572'}, {'text': 'Aza', 'type': 'Chemical', 'start': 1621, 'end': 1624, 'mesh': 'D001379'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 1642, 'end': 1654, 'mesh': 'D016572'}, {'text': 'CMV infection', 'type': 'Disease', 'start': 1693, 'end': 1706, 'mesh': 'D003586'}, {'text': 'Epstein Barr Virus infection', 'type': 'Disease', 'start': 1733, 'end': 1761, 'mesh': 'D020031'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 1785, 'end': 1797, 'mesh': 'D016572'}, {'text': 'lymphoma', 'type': 'Disease', 'start': 1867, 'end': 1875, 'mesh': 'D008223'}]"
+1237,6316193,"Structure-activity and dose-effect relationships of the antagonism of picrotoxin-induced seizures by cholecystokinin, fragments and analogues of cholecystokinin in mice.","Intraperitoneal administration of cholecystokinin octapeptide sulphate ester (CCK-8-SE) and nonsulphated cholecystokinin octapeptide (CCK-8-NS) enhanced the latency of seizures induced by picrotoxin in mice. Experiments with N- and C-terminal fragments revealed that the C-terminal tetrapeptide (CCK-5-8) was the active centre of the CCK octapeptide molecule. The analogues CCK-8-SE and CCK-8-NS (dose range 0.2-6.4 mumol/kg) and caerulein dose range 0.1-0.8 mumol/kg) showed bell-shaped dose-effect curves, with the greatest maximum inhibition for CCK-8-NS. The peptide CCK-5-8 had weak anticonvulsant activity in comparison to the octapeptides, 3.2 mumol/kg and larger doses of the reference drug, diazepam, totally prevented picrotoxin-induced seizures and mortality. The maximum effect of the peptides tested was less than that of diazepam. Experiments with analogues and derivatives of CCK-5-8 demonstrated that the effectiveness of the beta-alanyl derivatives of CCK-5-8 were enhanced and that they were equipotent with CCK-8-SE. Of the CCK-2-8 analogues, Ser(SO3H)7-Ac-CCK-2-8-SE and Thr(SO3H)7-Ac-CCK-2-8-SE and Hyp(SO3H)-Ac-CCK-2-8-SE were slightly more active than CCK-8-SE.","[{'text': 'picrotoxin', 'type': 'Chemical', 'start': 70, 'end': 80, 'mesh': 'D010852'}, {'text': 'seizures', 'type': 'Disease', 'start': 89, 'end': 97, 'mesh': 'D012640'}, {'text': 'cholecystokinin', 'type': 'Chemical', 'start': 101, 'end': 116, 'mesh': 'D002766'}, {'text': 'cholecystokinin', 'type': 'Chemical', 'start': 145, 'end': 160, 'mesh': 'D002766'}, {'text': 'cholecystokinin octapeptide', 'type': 'Chemical', 'start': 204, 'end': 231, 'mesh': 'D012844'}, {'text': 'CCK-8', 'type': 'Chemical', 'start': 248, 'end': 253, 'mesh': 'D012844'}, {'text': 'cholecystokinin octapeptide', 'type': 'Chemical', 'start': 275, 'end': 302, 'mesh': 'D012844'}, {'text': 'CCK-8', 'type': 'Chemical', 'start': 304, 'end': 309, 'mesh': 'D012844'}, {'text': 'seizures', 'type': 'Disease', 'start': 338, 'end': 346, 'mesh': 'D012640'}, {'text': 'picrotoxin', 'type': 'Chemical', 'start': 358, 'end': 368, 'mesh': 'D010852'}, {'text': 'CCK-8', 'type': 'Chemical', 'start': 544, 'end': 549, 'mesh': 'D012844'}, {'text': 'CCK-8', 'type': 'Chemical', 'start': 557, 'end': 562, 'mesh': 'D012844'}, {'text': 'caerulein', 'type': 'Chemical', 'start': 600, 'end': 609, 'mesh': 'D002108'}, {'text': 'CCK-8', 'type': 'Chemical', 'start': 719, 'end': 724, 'mesh': 'D012844'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 870, 'end': 878, 'mesh': 'D003975'}, {'text': 'picrotoxin', 'type': 'Chemical', 'start': 898, 'end': 908, 'mesh': 'D010852'}, {'text': 'seizures', 'type': 'Disease', 'start': 917, 'end': 925, 'mesh': 'D012640'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 1005, 'end': 1013, 'mesh': 'D003975'}, {'text': 'CCK-8', 'type': 'Chemical', 'start': 1196, 'end': 1201, 'mesh': 'D012844'}, {'text': 'CCK-8', 'type': 'Chemical', 'start': 1345, 'end': 1350, 'mesh': 'D012844'}]"
+1238,6321816,Vasopressin as a possible contributor to hypertension.,"The role of vasopressin as a pressor agent to the hypertensive process was examined. Vasopressin plays a major role in the pathogenesis of DOCA-salt hypertension, since the elevation of blood pressure was not substantial in the rats with lithium-treated diabetes insipidus after DOCA-salt treatment. Administration of DDAVP which has antidiuretic action but minimal vasopressor effect failed to increase blood pressure to the levels observed after administration of AVP. Furthermore, the pressor action of vasopressin appears to be important in the development of this model of hypertension, since the enhanced pressor responsiveness to the hormone was observed in the initial stage of hypertension. Increased secretion of vasopressin from neurohypophysis also promotes the function of the hormone as a pathogenetic factor in hypertension. An unproportional release of vasopressin compared to plasma osmolality may be induced by the absence of an adjusting control of angiotensin II forming and receptor binding capacity for sodium balance in the brain. However, the role of vasopressin remains to be determined in human essential hypertension.","[{'text': 'Vasopressin', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D014667'}, {'text': 'hypertension', 'type': 'Disease', 'start': 41, 'end': 53, 'mesh': 'D006973'}, {'text': 'vasopressin', 'type': 'Chemical', 'start': 67, 'end': 78, 'mesh': 'D014667'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 105, 'end': 117, 'mesh': 'D006973'}, {'text': 'Vasopressin', 'type': 'Chemical', 'start': 140, 'end': 151, 'mesh': 'D014667'}, {'text': 'DOCA', 'type': 'Chemical', 'start': 194, 'end': 198, 'mesh': 'D003900'}, {'text': 'hypertension', 'type': 'Disease', 'start': 204, 'end': 216, 'mesh': 'D006973'}, {'text': 'lithium', 'type': 'Chemical', 'start': 293, 'end': 300, 'mesh': 'D008094'}, {'text': 'diabetes insipidus', 'type': 'Disease', 'start': 309, 'end': 327, 'mesh': 'D003919'}, {'text': 'DOCA', 'type': 'Chemical', 'start': 334, 'end': 338, 'mesh': 'D003900'}, {'text': 'DDAVP', 'type': 'Chemical', 'start': 373, 'end': 378, 'mesh': 'D003894'}, {'text': 'vasopressin', 'type': 'Chemical', 'start': 561, 'end': 572, 'mesh': 'D014667'}, {'text': 'hypertension', 'type': 'Disease', 'start': 633, 'end': 645, 'mesh': 'D006973'}, {'text': 'hypertension', 'type': 'Disease', 'start': 741, 'end': 753, 'mesh': 'D006973'}, {'text': 'vasopressin', 'type': 'Chemical', 'start': 778, 'end': 789, 'mesh': 'D014667'}, {'text': 'hypertension', 'type': 'Disease', 'start': 881, 'end': 893, 'mesh': 'D006973'}, {'text': 'vasopressin', 'type': 'Chemical', 'start': 924, 'end': 935, 'mesh': 'D014667'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 1023, 'end': 1034, 'mesh': 'D000809'}, {'text': 'sodium', 'type': 'Chemical', 'start': 1080, 'end': 1086, 'mesh': 'D012964'}, {'text': 'vasopressin', 'type': 'Chemical', 'start': 1130, 'end': 1141, 'mesh': 'D014667'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1186, 'end': 1198, 'mesh': 'D006973'}]"
+1239,6453500,Toxic hepatitis induced by disulfiram in a non-alcoholic.,A reversible toxic liver damage was observed in a non-alcoholic woman treated with disulfiram. The causative relationship was proven by challenge.,"[{'text': 'Toxic hepatitis', 'type': 'Disease', 'start': 0, 'end': 15, 'mesh': 'D056486'}, {'text': 'disulfiram', 'type': 'Chemical', 'start': 27, 'end': 37, 'mesh': 'D004221'}, {'text': 'toxic liver damage', 'type': 'Disease', 'start': 71, 'end': 89, 'mesh': 'D056486'}, {'text': 'disulfiram', 'type': 'Chemical', 'start': 141, 'end': 151, 'mesh': 'D004221'}]"
+1240,6517710,Atrial thrombosis involving the heart of F-344 rats ingesting quinacrine hydrochloride.,"Quinacrine hydrochloride is toxic for the heart of F-344 rats. Rats treated with 500 ppm quinacrine hydrochloride in the diet all developed a high incidence of left atrial thrombosis. The lesion was associated with cardiac hypertrophy and dilatation and focal myocardial degeneration. Rats died from cardiac hypertrophy with severe acute and chronic congestion of the lungs, liver, and other organs. Seventy percent of rats given 250 ppm quinacrine hydrochloride and 1,000 ppm sodium nitrite simultaneously in the diet had thrombosis of the atria of the heart, while untreated control rats in this laboratory did not have atrial thrombosis. Sodium nitrite in combination with quinacrine hydrochloride appeared to have no additional effect.","[{'text': 'Atrial thrombosis', 'type': 'Disease', 'start': 0, 'end': 17, 'mesh': 'D003328'}, {'text': 'quinacrine hydrochloride', 'type': 'Chemical', 'start': 62, 'end': 86, 'mesh': 'D011796'}, {'text': 'Quinacrine hydrochloride', 'type': 'Chemical', 'start': 88, 'end': 112, 'mesh': 'D011796'}, {'text': 'quinacrine hydrochloride', 'type': 'Chemical', 'start': 177, 'end': 201, 'mesh': 'D011796'}, {'text': 'atrial thrombosis', 'type': 'Disease', 'start': 253, 'end': 270, 'mesh': 'D003328'}, {'text': 'cardiac hypertrophy', 'type': 'Disease', 'start': 303, 'end': 322, 'mesh': 'D006332'}, {'text': 'myocardial degeneration', 'type': 'Disease', 'start': 348, 'end': 371, 'mesh': 'D009202'}, {'text': 'cardiac hypertrophy', 'type': 'Disease', 'start': 388, 'end': 407, 'mesh': 'D006332'}, {'text': 'quinacrine hydrochloride', 'type': 'Chemical', 'start': 526, 'end': 550, 'mesh': 'D011796'}, {'text': 'sodium nitrite', 'type': 'Chemical', 'start': 565, 'end': 579, 'mesh': 'D012977'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 611, 'end': 621, 'mesh': 'D013927'}, {'text': 'atrial thrombosis', 'type': 'Disease', 'start': 710, 'end': 727, 'mesh': 'D003328'}, {'text': 'Sodium nitrite', 'type': 'Chemical', 'start': 729, 'end': 743, 'mesh': 'D012977'}, {'text': 'quinacrine hydrochloride', 'type': 'Chemical', 'start': 764, 'end': 788, 'mesh': 'D011796'}]"
+1241,6529939,Alternating sinus rhythm and intermittent sinoatrial block induced by propranolol.,"Alternating sinus rhythm and intermittent sinoatrial (S-A) block was observed in a 57-year-old woman, under treatment for angina with 80 mg propranolol daily. The electrocardiogram showed alternation of long and short P-P intervals and occasional pauses. These pauses were always preceded by the short P-P intervals and were usually followed by one or two P-P intervals of 0.92-0.95 s representing the basic sinus cycle. Following these basic sinus cycles, alternating rhythm started with the longer P-P interval. The long P-P intervals ranged between 1.04-1.12 s and the short P-P intervals between 0.80-0.84 s, respectively. The duration of the pauses were equal or almost equal to one short plus one long P-P interval or to twice the basic sinus cycle. In one recording a short period of regular sinus rhythm with intermittent 2/1 S-A block was observed. This short period of sinus rhythm was interrupted by sudden prolongation of the P-P interval starting the alternative rhythm. There were small changes in the shape of the P waves and P-R intervals. S-A conduction through two pathways, the first with 2/1 block the second having 0.12-0.14 s longer conduction time and with occasional 2/1 block was proposed for the explanation of the alternating P-P interval and other electrocardiographic features seen. Atropine 1 mg given intravenously resulted in shortening of all P-P intervals without changing the rhythm. The abnormal rhythm disappeared with the withdrawal of propranolol and when the drug was restarted a 2/1 S-A block was seen. This was accepted as evidence for propranolol being the cause of this conduction disorder.","[{'text': 'Alternating sinus rhythm', 'type': 'Disease', 'start': 0, 'end': 24, 'mesh': 'D001146'}, {'text': 'sinoatrial block', 'type': 'Disease', 'start': 42, 'end': 58, 'mesh': 'D012848'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 70, 'end': 81, 'mesh': 'D011433'}, {'text': 'Alternating sinus rhythm', 'type': 'Disease', 'start': 83, 'end': 107, 'mesh': 'D001146'}, {'text': 'sinoatrial (S-A) block', 'type': 'Disease', 'start': 125, 'end': 147, 'mesh': 'D012848'}, {'text': 'angina', 'type': 'Disease', 'start': 205, 'end': 211, 'mesh': 'D000787'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 223, 'end': 234, 'mesh': 'D011433'}, {'text': 'alternating rhythm', 'type': 'Disease', 'start': 540, 'end': 558, 'mesh': 'D001146'}, {'text': 'S-A block', 'type': 'Disease', 'start': 917, 'end': 926, 'mesh': 'D012848'}, {'text': 'Atropine', 'type': 'Chemical', 'start': 1395, 'end': 1403, 'mesh': 'D001285'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 1557, 'end': 1568, 'mesh': 'D011433'}, {'text': 'S-A block', 'type': 'Disease', 'start': 1607, 'end': 1616, 'mesh': 'D012848'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 1661, 'end': 1672, 'mesh': 'D011433'}, {'text': 'conduction disorder', 'type': 'Disease', 'start': 1697, 'end': 1716, 'mesh': 'D019955'}]"
+1242,6585590,"Antitumor effect, cardiotoxicity, and nephrotoxicity of doxorubicin in the IgM solid immunocytoma-bearing LOU/M/WSL rat.","Antitumor activity, cardiotoxicity, and nephrotoxicity induced by doxorubicin were studied in LOU/M/WSL inbred rats each bearing a transplantable solid IgM immunocytoma. Animals with a tumor (diameter, 15.8 +/- 3.3 mm) were treated with iv injections of doxorubicin on 5 consecutive days, followed by 1 weekly injection for 7 weeks (dose range, 0.015-4.0 mg/kg body wt). Tumor regression was observed with 0.5 mg doxorubicin/kg. Complete disappearance of the tumor was induced with 1.0 mg doxorubicin/kg. Histologic evidence of cardiotoxicity scored as grade III was only observed at a dose of 1.0 mg doxorubicin/kg. Light microscopic evidence of renal damage was seen above a dose of 0.5 mg doxorubicin/kg, which resulted in albuminuria and very low serum albumin levels. In the group that received 1.0 mg doxorubicin/kg, the serum albumin level decreased from 33.6 +/- 4.1 to 1.5 +/- 0.5 g/liter. Ascites and hydrothorax were observed simultaneously. The same experiments were performed with non-tumor-bearing rats, in which no major differences were observed. In conclusion, antitumor activity, cardiotoxicity, and nephrotoxicity were studied simultaneously in the same LOU/M/WSL rat. Albuminuria due to renal damage led to extremely low serum albumin levels, so ascites and hydrothorax were not necessarily a consequence of the observed cardiomyopathy.","[{'text': 'cardiotoxicity', 'type': 'Disease', 'start': 18, 'end': 32, 'mesh': 'D066126'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 38, 'end': 52, 'mesh': 'D007674'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 56, 'end': 67, 'mesh': 'D004317'}, {'text': 'immunocytoma', 'type': 'Disease', 'start': 85, 'end': 97, 'mesh': '-1'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 141, 'end': 155, 'mesh': 'D066126'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 161, 'end': 175, 'mesh': 'D007674'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 187, 'end': 198, 'mesh': 'D004317'}, {'text': 'immunocytoma', 'type': 'Disease', 'start': 277, 'end': 289, 'mesh': '-1'}, {'text': 'tumor', 'type': 'Disease', 'start': 306, 'end': 311, 'mesh': 'D009369'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 375, 'end': 386, 'mesh': 'D004317'}, {'text': 'Tumor', 'type': 'Disease', 'start': 492, 'end': 497, 'mesh': 'D009369'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 534, 'end': 545, 'mesh': 'D004317'}, {'text': 'tumor', 'type': 'Disease', 'start': 580, 'end': 585, 'mesh': 'D009369'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 610, 'end': 621, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 649, 'end': 663, 'mesh': 'D066126'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 722, 'end': 733, 'mesh': 'D004317'}, {'text': 'renal damage', 'type': 'Disease', 'start': 768, 'end': 780, 'mesh': 'D007674'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 813, 'end': 824, 'mesh': 'D004317'}, {'text': 'albuminuria', 'type': 'Disease', 'start': 847, 'end': 858, 'mesh': 'D000419'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 928, 'end': 939, 'mesh': 'D004317'}, {'text': 'Ascites', 'type': 'Disease', 'start': 1020, 'end': 1027, 'mesh': 'D001201'}, {'text': 'hydrothorax', 'type': 'Disease', 'start': 1032, 'end': 1043, 'mesh': 'D006876'}, {'text': 'tumor', 'type': 'Disease', 'start': 1119, 'end': 1124, 'mesh': 'D009369'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1219, 'end': 1233, 'mesh': 'D066126'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1239, 'end': 1253, 'mesh': 'D007674'}, {'text': 'Albuminuria', 'type': 'Disease', 'start': 1309, 'end': 1320, 'mesh': 'D000419'}, {'text': 'renal damage', 'type': 'Disease', 'start': 1328, 'end': 1340, 'mesh': 'D007674'}, {'text': 'ascites', 'type': 'Disease', 'start': 1387, 'end': 1394, 'mesh': 'D001201'}, {'text': 'hydrothorax', 'type': 'Disease', 'start': 1399, 'end': 1410, 'mesh': 'D006876'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 1462, 'end': 1476, 'mesh': 'D009202'}]"
+1243,6615679,Intraoperative bradycardia and hypotension associated with timolol and pilocarpine eye drops.,"A 69-yr-old man, who was concurrently being treated with pilocarpine nitrate and timolol maleate eye drops, developed a bradycardia and became hypotensive during halothane anaesthesia. Both timolol and pilocarpine were subsequently identified in a 24-h collection of urine. Timolol (but not pilocarpine) was detected in a sample of plasma removed during surgery; the plasma concentration of timolol (2.6 ng ml-1) was consistent with partial beta-adrenoceptor blockade. It is postulated that this action may have been enhanced during halothane anaesthesia with resultant bradycardia and hypotension. Pilocarpine may have had a contributory effect.","[{'text': 'bradycardia', 'type': 'Disease', 'start': 15, 'end': 26, 'mesh': 'D001919'}, {'text': 'hypotension', 'type': 'Disease', 'start': 31, 'end': 42, 'mesh': 'D007022'}, {'text': 'timolol', 'type': 'Chemical', 'start': 59, 'end': 66, 'mesh': 'D013999'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 71, 'end': 82, 'mesh': 'D010862'}, {'text': 'pilocarpine nitrate', 'type': 'Chemical', 'start': 151, 'end': 170, 'mesh': 'D010862'}, {'text': 'timolol maleate', 'type': 'Chemical', 'start': 175, 'end': 190, 'mesh': 'D013999'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 214, 'end': 225, 'mesh': 'D001919'}, {'text': 'hypotensive', 'type': 'Disease', 'start': 237, 'end': 248, 'mesh': 'D007022'}, {'text': 'halothane', 'type': 'Chemical', 'start': 256, 'end': 265, 'mesh': 'D006221'}, {'text': 'timolol', 'type': 'Chemical', 'start': 284, 'end': 291, 'mesh': 'D013999'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 296, 'end': 307, 'mesh': 'D010862'}, {'text': 'Timolol', 'type': 'Chemical', 'start': 368, 'end': 375, 'mesh': 'D013999'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 385, 'end': 396, 'mesh': 'D010862'}, {'text': 'timolol', 'type': 'Chemical', 'start': 485, 'end': 492, 'mesh': 'D013999'}, {'text': 'halothane', 'type': 'Chemical', 'start': 627, 'end': 636, 'mesh': 'D006221'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 664, 'end': 675, 'mesh': 'D001919'}, {'text': 'hypotension', 'type': 'Disease', 'start': 680, 'end': 691, 'mesh': 'D007022'}, {'text': 'Pilocarpine', 'type': 'Chemical', 'start': 693, 'end': 704, 'mesh': 'D010862'}]"
+1244,6627074,Succinylcholine apnoea: attempted reversal with anticholinesterases.,"Anticholinesterases were administered in an attempt to antagonize prolonged neuromuscular blockade following the administration of succinylcholine in a patient later found to be homozygous for atypical plasma cholinesterase. Edrophonium 10 mg, given 74 min after succinylcholine, when train-of-four stimulation was characteristic of phase II block, produced partial antagonism which was not sustained. Repeated doses of edrophonium to 70 mg and neostigmine to 2.5 mg did not antagonize or augment the block. Spontaneous respiration recommenced 200 min after succinylcholine administration. It is concluded that anticholinesterases are only partially effective in restoring neuromuscular function in succinylcholine apnoea despite muscle twitch activity typical of phase II block.","[{'text': 'Succinylcholine', 'type': 'Chemical', 'start': 0, 'end': 15, 'mesh': 'D013390'}, {'text': 'apnoea', 'type': 'Disease', 'start': 16, 'end': 22, 'mesh': 'D001049'}, {'text': 'neuromuscular blockade', 'type': 'Disease', 'start': 145, 'end': 167, 'mesh': 'D020879'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 200, 'end': 215, 'mesh': 'D013390'}, {'text': 'Edrophonium', 'type': 'Chemical', 'start': 294, 'end': 305, 'mesh': 'D004491'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 332, 'end': 347, 'mesh': 'D013390'}, {'text': 'edrophonium', 'type': 'Chemical', 'start': 489, 'end': 500, 'mesh': 'D004491'}, {'text': 'neostigmine', 'type': 'Chemical', 'start': 514, 'end': 525, 'mesh': 'D009388'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 627, 'end': 642, 'mesh': 'D013390'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 768, 'end': 783, 'mesh': 'D013390'}, {'text': 'apnoea', 'type': 'Disease', 'start': 784, 'end': 790, 'mesh': 'D001049'}]"
+1245,6631522,Effect of doxorubicin on [omega-I-131]heptadecanoic acid myocardial scintigraphy and echocardiography in dogs.,"The effects of serial treatment with doxorubicin on dynamic myocardial scintigraphy with [omega-I-131]heptadecanoic acid (I-131 HA), and on global left-ventricular function determined echocardiographically, were studied in a group of nine mongrel dogs. Total extractable myocardial lipid was compared postmortem between a group of control dogs and doxorubicin-treated dogs. A significant and then progressive fall in global LV function was observed at a cumulative doxorubicin dose of 4 mg/kg. A significant increase in the myocardial t1/2 of the I-131 HA was observed only at a higher cumulative dose, 10 mg/kg. No significant alteration in total extractable myocardial lipids was observed between control dogs and those treated with doxorubicin. Our findings suggest that the changes leading to an alteration of myocardial dynamic imaging with I-131 HA are not the initiating factor in doxorubicin cardiotoxicity.","[{'text': 'doxorubicin', 'type': 'Chemical', 'start': 10, 'end': 21, 'mesh': 'D004317'}, {'text': '[omega-I-131]heptadecanoic acid', 'type': 'Chemical', 'start': 25, 'end': 56, 'mesh': 'C013102'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 148, 'end': 159, 'mesh': 'D004317'}, {'text': '[omega-I-131]heptadecanoic acid', 'type': 'Chemical', 'start': 200, 'end': 231, 'mesh': 'C013102'}, {'text': 'I-131 HA', 'type': 'Chemical', 'start': 233, 'end': 241, 'mesh': 'C013102'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 459, 'end': 470, 'mesh': 'D004317'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 576, 'end': 587, 'mesh': 'D004317'}, {'text': 'I-131 HA', 'type': 'Chemical', 'start': 658, 'end': 666, 'mesh': 'C013102'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 846, 'end': 857, 'mesh': 'D004317'}, {'text': 'I-131 HA', 'type': 'Chemical', 'start': 957, 'end': 965, 'mesh': 'C013102'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 999, 'end': 1010, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1011, 'end': 1025, 'mesh': 'D066126'}]"
+1246,6673474,Hemodynamics and myocardial metabolism under deliberate hypotension. An experimental study in dogs.,"Coronary blood flow, cardiac work and metabolism were studied in dogs under sodium nitroprusside (SNP) and trimetaphan (TMP) deliberate hypotension (20% and 40% mean pressure decrease from baseline). Regarding the effects of drug-induced hypotension on coronary blood flow, aortic and coronary sinus metabolic data (pH, pO2, pCO2) we could confirm that nitroprusside hypotension could be safely used to 30% mean blood pressure decrease from control, trimetaphan hypotension to 20% mean blood pressure decrease. Cardiac work was significantly reduced during SNP hypotension. Myocardial O2 consumption and O2 availability were directly dependent on the coronary perfusion. Careful invasive monitoring of the blood pressure, blood gases and of the ECG ST-T segment is mandatory.","[{'text': 'hypotension', 'type': 'Disease', 'start': 56, 'end': 67, 'mesh': 'D007022'}, {'text': 'sodium nitroprusside', 'type': 'Chemical', 'start': 176, 'end': 196, 'mesh': 'D009599'}, {'text': 'SNP', 'type': 'Chemical', 'start': 198, 'end': 201, 'mesh': 'D009599'}, {'text': 'trimetaphan', 'type': 'Chemical', 'start': 207, 'end': 218, 'mesh': 'D014294'}, {'text': 'TMP', 'type': 'Chemical', 'start': 220, 'end': 223, 'mesh': 'D014294'}, {'text': 'hypotension', 'type': 'Disease', 'start': 236, 'end': 247, 'mesh': 'D007022'}, {'text': 'hypotension', 'type': 'Disease', 'start': 338, 'end': 349, 'mesh': 'D007022'}, {'text': 'nitroprusside', 'type': 'Chemical', 'start': 453, 'end': 466, 'mesh': 'D009599'}, {'text': 'hypotension', 'type': 'Disease', 'start': 467, 'end': 478, 'mesh': 'D007022'}, {'text': 'trimetaphan', 'type': 'Chemical', 'start': 550, 'end': 561, 'mesh': 'D014294'}, {'text': 'hypotension', 'type': 'Disease', 'start': 562, 'end': 573, 'mesh': 'D007022'}, {'text': 'SNP', 'type': 'Chemical', 'start': 657, 'end': 660, 'mesh': 'D009599'}, {'text': 'hypotension', 'type': 'Disease', 'start': 661, 'end': 672, 'mesh': 'D007022'}, {'text': 'O2', 'type': 'Chemical', 'start': 685, 'end': 687, 'mesh': 'D010100'}, {'text': 'O2', 'type': 'Chemical', 'start': 704, 'end': 706, 'mesh': 'D010100'}]"
+1247,6687006,Evidence for a selective brain noradrenergic involvement in the locomotor stimulant effects of amphetamine in the rat.,"Male rats received the noradrenaline neurotoxin DSP4 (50 mg/kg) 7 days prior to injection of D-amphetamine (10 or 40 mumol/kg i.p.). The hyperactivity induced by D-amphetamine (10 mumol/kg) was significantly reduced by DSP4 pretreatment. However, the increased rearings and the amphetamine-induced stereotypies were not blocked by pretreatment with DSP4. The reduction of amphetamine hyperactivity induced by DSP4 was blocked by pretreatment with the noradrenaline-uptake blocking agent, desipramine, which prevents the neurotoxic action of DSP4. The present results suggest a selective involvement of central noradrenergic neurones in the locomotor stimulant effect of amphetamine in the rat.","[{'text': 'amphetamine', 'type': 'Chemical', 'start': 95, 'end': 106, 'mesh': 'D000661'}, {'text': 'noradrenaline', 'type': 'Chemical', 'start': 142, 'end': 155, 'mesh': 'D009638'}, {'text': 'DSP4', 'type': 'Chemical', 'start': 167, 'end': 171, 'mesh': 'C012102'}, {'text': 'D-amphetamine', 'type': 'Chemical', 'start': 212, 'end': 225, 'mesh': 'D003913'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 256, 'end': 269, 'mesh': 'D006948'}, {'text': 'D-amphetamine', 'type': 'Chemical', 'start': 281, 'end': 294, 'mesh': 'D003913'}, {'text': 'DSP4', 'type': 'Chemical', 'start': 338, 'end': 342, 'mesh': 'C012102'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 397, 'end': 408, 'mesh': 'D000661'}, {'text': 'stereotypies', 'type': 'Disease', 'start': 417, 'end': 429, 'mesh': 'D019956'}, {'text': 'DSP4', 'type': 'Chemical', 'start': 468, 'end': 472, 'mesh': 'C012102'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 491, 'end': 502, 'mesh': 'D000661'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 503, 'end': 516, 'mesh': 'D006948'}, {'text': 'DSP4', 'type': 'Chemical', 'start': 528, 'end': 532, 'mesh': 'C012102'}, {'text': 'noradrenaline', 'type': 'Chemical', 'start': 570, 'end': 583, 'mesh': 'D009638'}, {'text': 'desipramine', 'type': 'Chemical', 'start': 607, 'end': 618, 'mesh': 'D003891'}, {'text': 'neurotoxic', 'type': 'Disease', 'start': 639, 'end': 649, 'mesh': 'D020258'}, {'text': 'DSP4', 'type': 'Chemical', 'start': 660, 'end': 664, 'mesh': 'C012102'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 789, 'end': 800, 'mesh': 'D000661'}]"
+1248,6695685,Accelerated junctional rhythms during oral verapamil therapy.,"This study examined the frequency of atrioventricular (AV) dissociation and accelerated junctional rhythms in 59 patients receiving oral verapamil. Accelerated junctional rhythms and AV dissociation were frequent in patients with supraventricular tachyarrhythmias, particularly AV nodal reentry. Verapamil administration to these patients led to an asymptomatic increase in activity of these junctional pacemakers. In patients with various chest pain syndromes, verapamil neither increased the frequency of junctional rhythms nor suppressed their role as escape rhythms under physiologically appropriate circumstances.","[{'text': 'Accelerated junctional rhythms', 'type': 'Disease', 'start': 0, 'end': 30, 'mesh': 'D001145'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 43, 'end': 52, 'mesh': 'D014700'}, {'text': 'accelerated junctional rhythms', 'type': 'Disease', 'start': 138, 'end': 168, 'mesh': 'D001145'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 199, 'end': 208, 'mesh': 'D014700'}, {'text': 'Accelerated junctional rhythms', 'type': 'Disease', 'start': 210, 'end': 240, 'mesh': 'D001145'}, {'text': 'supraventricular tachyarrhythmias', 'type': 'Disease', 'start': 292, 'end': 325, 'mesh': 'D013617'}, {'text': 'Verapamil', 'type': 'Chemical', 'start': 358, 'end': 367, 'mesh': 'D014700'}, {'text': 'chest pain', 'type': 'Disease', 'start': 502, 'end': 512, 'mesh': 'D002637'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 524, 'end': 533, 'mesh': 'D014700'}]"
+1249,6806735,"Treatment of ovarian cancer with a combination of cis-platinum, adriamycin, cyclophosphamide and hexamethylmelamine.","During the last 2 1/2 years, 38 patients with ovarian cancer were treated with a combination of cisplatinum (CPDD), 50 mg/m2, adriamycin, 30 mg/m2, cyclophosphamide, 300 mg/m2, on day 1; and hexamethylmelamine (HMM), 6 mg/kg daily, for 14 days. Each course was repeated monthly. 2 patients had stage II, 14 stage III and 22 stage IV disease. 14 of the 38 patients were previously treated with chemotherapy, 1 with radiation, 6 with both chemotherapy and radiation, and 17 did not have any treatment before CPDD combination. 31 of the 38 cases (81.5%) demonstrated objective responses lasting for 2 months or more. These responses were partial in 19 and complete in 12 cases. Hematologic toxicity was moderate and with reversible anemia developing in 71% of patients. Gastrointestinal side effects from CPDD were universal. HMM gastrointestinal toxicity necessitated discontinuation of the drug in 5 patients. Severe nephrotoxicity was observed in 2 patients but was reversible. There were no drug-related deaths.","[{'text': 'ovarian cancer', 'type': 'Disease', 'start': 13, 'end': 27, 'mesh': 'D010051'}, {'text': 'cis-platinum', 'type': 'Chemical', 'start': 50, 'end': 62, 'mesh': 'D002945'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 64, 'end': 74, 'mesh': 'D004317'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 76, 'end': 92, 'mesh': 'D003520'}, {'text': 'hexamethylmelamine', 'type': 'Chemical', 'start': 97, 'end': 115, 'mesh': 'D006585'}, {'text': 'ovarian cancer', 'type': 'Disease', 'start': 163, 'end': 177, 'mesh': 'D010051'}, {'text': 'cisplatinum', 'type': 'Chemical', 'start': 213, 'end': 224, 'mesh': 'D002945'}, {'text': 'CPDD', 'type': 'Chemical', 'start': 226, 'end': 230, 'mesh': 'C034868'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 243, 'end': 253, 'mesh': 'D004317'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 265, 'end': 281, 'mesh': 'D003520'}, {'text': 'hexamethylmelamine', 'type': 'Chemical', 'start': 308, 'end': 326, 'mesh': 'D006585'}, {'text': 'HMM', 'type': 'Chemical', 'start': 328, 'end': 331, 'mesh': 'D006585'}, {'text': 'CPDD', 'type': 'Chemical', 'start': 623, 'end': 627, 'mesh': 'C034868'}, {'text': 'Hematologic toxicity', 'type': 'Disease', 'start': 792, 'end': 812, 'mesh': 'D006402'}, {'text': 'anemia', 'type': 'Disease', 'start': 846, 'end': 852, 'mesh': 'D000740'}, {'text': 'CPDD', 'type': 'Chemical', 'start': 919, 'end': 923, 'mesh': 'C034868'}, {'text': 'HMM', 'type': 'Chemical', 'start': 940, 'end': 943, 'mesh': 'D006585'}, {'text': 'gastrointestinal toxicity', 'type': 'Disease', 'start': 944, 'end': 969, 'mesh': 'D005767'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1033, 'end': 1047, 'mesh': 'D007674'}]"
+1250,6884395,Nontraumatic dissecting aneurysm of the basilar artery.,"A case of nontraumatic dissecting aneurysm of the basilar artery in association with hypertension, smoke, and oral contraceptives is reported in a young female patient with a locked-in syndrome.","[{'text': 'dissecting aneurysm', 'type': 'Disease', 'start': 13, 'end': 32, 'mesh': 'D000784'}, {'text': 'dissecting aneurysm', 'type': 'Disease', 'start': 79, 'end': 98, 'mesh': 'D000784'}, {'text': 'hypertension', 'type': 'Disease', 'start': 141, 'end': 153, 'mesh': 'D006973'}, {'text': 'oral contraceptives', 'type': 'Chemical', 'start': 166, 'end': 185, 'mesh': 'D003276'}, {'text': 'locked-in syndrome', 'type': 'Disease', 'start': 231, 'end': 249, 'mesh': 'D011782'}]"
+1251,6893265,Propylthiouracil-induced hepatic damage.,"Two cases of propylthiouracil-induced liver damage have been observed. The first case is of an acute type of damage, proven by rechallenge; the second presents a clinical and histologic picture resembling chronic active hepatitis, with spontaneous remission.","[{'text': 'Propylthiouracil', 'type': 'Chemical', 'start': 0, 'end': 16, 'mesh': 'D011441'}, {'text': 'hepatic damage', 'type': 'Disease', 'start': 25, 'end': 39, 'mesh': 'D056486'}, {'text': 'propylthiouracil', 'type': 'Chemical', 'start': 54, 'end': 70, 'mesh': 'D011441'}, {'text': 'liver damage', 'type': 'Disease', 'start': 79, 'end': 91, 'mesh': 'D056486'}, {'text': 'chronic active hepatitis', 'type': 'Disease', 'start': 246, 'end': 270, 'mesh': 'D006521'}]"
+1252,6985297,Studies on the bradycardia induced by bepridil.,"Bepridil, a novel active compound for prophylactic treatment of anginal attacks, induced persistent bradycardia and a non-specific anti-tachycardial effect, the mechanisms of which were investigated in vitro and in vivo. In vitro perfusion of bepridil in the life-support medium for isolated sino-atrial tissue from rabbit heart, caused a reduction in action potential (AP) spike frequency (recorded by KCl microelectrodes) starting at doses of 5 X 10(-6) M. This effect was dose-dependent up to concentrations of 5 X 10(-5) M, whereupon blockade of sinus activity set in. Bepridil at a dose of 5 X 10(-6) M, induced a concomitant reduction in AP amplitude (falling from 71 +/- 8 mV to 47 +/- 6 mV), maximum systolic depolarization velocity (phase 0) which fell from 1.85 +/- 0.35 V/s to 0.84 +/- 0.28 V/s, together with maximum diastolic depolarization velocity (phase 4) which fell from 38 +/- 3 mV/s to 24 +/- 5 mV/s. In vivo injection of bepridil at a dose of 5 mg/kg (i.v.) into 6 anaesthetized dogs which had undergone ablation of all the extrinsic cardiac afferent nerve supply, together with a bilateral medullo-adrenalectomy, caused a marked reduction in heart rate which fell from 98.7 +/- 4.2 beats/min to 76 +/- 5.3 beats/min sustained for more than 45 min. It is concluded that bepridil reduces heart rate by acting directly on the sinus node. This effect, which results in a flattening of the phase 0 and phase 4 slope, together with a longer AP duration, may be due to an increase in the time constants of slow inward ionic currents (already demonstrated elsewhere), but also to an increased time constant for deactivation of the outward potassium current (Ip).","[{'text': 'bradycardia', 'type': 'Disease', 'start': 15, 'end': 26, 'mesh': 'D001919'}, {'text': 'bepridil', 'type': 'Chemical', 'start': 38, 'end': 46, 'mesh': 'D015764'}, {'text': 'Bepridil', 'type': 'Chemical', 'start': 48, 'end': 56, 'mesh': 'D015764'}, {'text': 'anginal attacks', 'type': 'Disease', 'start': 112, 'end': 127, 'mesh': 'D000787'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 148, 'end': 159, 'mesh': 'D001919'}, {'text': 'tachycardial', 'type': 'Disease', 'start': 184, 'end': 196, 'mesh': 'D013610'}, {'text': 'bepridil', 'type': 'Chemical', 'start': 291, 'end': 299, 'mesh': 'D015764'}, {'text': 'KCl', 'type': 'Chemical', 'start': 451, 'end': 454, 'mesh': 'D011189'}, {'text': 'Bepridil', 'type': 'Chemical', 'start': 621, 'end': 629, 'mesh': 'D015764'}, {'text': 'bepridil', 'type': 'Chemical', 'start': 990, 'end': 998, 'mesh': 'D015764'}, {'text': 'bepridil', 'type': 'Chemical', 'start': 1339, 'end': 1347, 'mesh': 'D015764'}, {'text': 'potassium', 'type': 'Chemical', 'start': 1701, 'end': 1710, 'mesh': 'D011188'}]"
+1253,6985498,Hepatitis and renal tubular acidosis after anesthesia with methoxyflurane.,A 69-year-old man operated for acute cholecystitis under methoxyflurane anesthesia developed postoperatively a hepatic insufficiency syndrome and renal tubular acidosis. Massive bleeding appeared during surgery which lasted for six hours. Postoperative evolution under supportive therapy was favourable. Complete recovery was confirmed by repeated controls performed over a period of one year after surgery.,"[{'text': 'Hepatitis', 'type': 'Disease', 'start': 0, 'end': 9, 'mesh': 'D056486'}, {'text': 'renal tubular acidosis', 'type': 'Disease', 'start': 14, 'end': 36, 'mesh': 'D000141'}, {'text': 'methoxyflurane', 'type': 'Chemical', 'start': 59, 'end': 73, 'mesh': 'D008733'}, {'text': 'acute cholecystitis', 'type': 'Disease', 'start': 106, 'end': 125, 'mesh': 'D041881'}, {'text': 'methoxyflurane', 'type': 'Chemical', 'start': 132, 'end': 146, 'mesh': 'D008733'}, {'text': 'hepatic insufficiency syndrome', 'type': 'Disease', 'start': 186, 'end': 216, 'mesh': 'D048550'}, {'text': 'renal tubular acidosis', 'type': 'Disease', 'start': 221, 'end': 243, 'mesh': 'D000141'}, {'text': 'bleeding', 'type': 'Disease', 'start': 253, 'end': 261, 'mesh': 'D006470'}]"
+1254,7018927,Pituitary response to luteinizing hormone-releasing hormone during haloperidol-induced hyperprolactinemia.,"The effects of a 6-hour infusion with haloperidol on serum prolactin and luteinizing hormone (LH) levels was studied in a group of male subjects. Five hours after starting the infusions, a study of the pituitary responses to LH-releasing hormone (LH-RH) was carried out. Control patients received infusions of 0.9% NaCl solution. During the course of haloperidol infusions, significant hyperprolactinemia was found, together with an abolished pituitary response to LH-RH, as compared with responses of control subjects.","[{'text': 'haloperidol', 'type': 'Chemical', 'start': 67, 'end': 78, 'mesh': 'D006220'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 87, 'end': 105, 'mesh': 'D006966'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 145, 'end': 156, 'mesh': 'D006220'}, {'text': 'NaCl', 'type': 'Chemical', 'start': 422, 'end': 426, 'mesh': 'D012965'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 458, 'end': 469, 'mesh': 'D006220'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 493, 'end': 511, 'mesh': 'D006966'}]"
+1255,7121659,Antirifampicin antibodies in acute rifampicin-associated renal failure.,"5 patients with acute renal failure (3 with thrombopenia and hemolysis) induced by the reintroduction of rifampicin are described. No correlation was found between the severity of clinical manifestations and the total dose taken by the patients. In all but 1 patient, antirifampicin antibodies were detected. Antibodies suggested to be of the IgM class were detected in all 3 patients with hematological disorders. The pattern of non-specific acute tubular necrosis found in the 2 biopsied patients, indistinguishable from that of ischemic origin, raised the possibility of a vascular-mediated damage. In 3 patients, the possibility of a triggering immunoallergic mechanism is discussed.","[{'text': 'rifampicin', 'type': 'Chemical', 'start': 35, 'end': 45, 'mesh': 'D012293'}, {'text': 'renal failure', 'type': 'Disease', 'start': 57, 'end': 70, 'mesh': 'D051437'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 88, 'end': 107, 'mesh': 'D058186'}, {'text': 'thrombopenia', 'type': 'Disease', 'start': 116, 'end': 128, 'mesh': 'D013921'}, {'text': 'hemolysis', 'type': 'Disease', 'start': 133, 'end': 142, 'mesh': 'D006461'}, {'text': 'rifampicin', 'type': 'Chemical', 'start': 177, 'end': 187, 'mesh': 'D012293'}, {'text': 'hematological disorders', 'type': 'Disease', 'start': 462, 'end': 485, 'mesh': 'D006402'}, {'text': 'acute tubular necrosis', 'type': 'Disease', 'start': 515, 'end': 537, 'mesh': 'D007683'}]"
+1256,7147232,Cardiovascular effects of hypotension induced by adenosine triphosphate and sodium nitroprusside on dogs with denervated hearts.,"Adenosine triphosphate (ATP) and sodium nitroprusside (SNP) are administered to patients to induce and control hypotension during anesthesia. SNP is authorized for clinical use in USA and UK, and ATP is clinically used in other countries such as Japan. We investigated how these two drugs act on the cardiovascular systems of 20 dogs whose hearts had been denervated by a procedure we had devised. ATP (10 dogs) or SNP (10 dogs) was administered to reduce mean arterial pressure by 30% to 70% of control. Before, during and after induced hypotension, we measured major cardiovascular parameters. Hypotension induced by ATP was accompanied by significant decreases in mean pulmonary arterial pressure (p less than 0.001), central venous pressure (p less than 0.001), left ventricular end-diastolic pressure (p less than 0.001), total peripheral resistance (p less than 0.001), rate pressure product (p less than 0.001), total body oxygen consumption (p less than 0.05), and heart rate (p less than 0.001); all these variables returned normal within 30 min after ATP was stopped. Cardiac output did not change. During hypotension produced by SNP similar decreases were observed in mean pulmonary arterial pressure (p less than 0.01), central venous pressure (p less than 0.001), left ventricular end-diastolic pressure (p less than 0.01), total peripheral resistance (p less than 0.001), rate pressure product (p less than 0.001), and oxygen content difference between arterial and mixed venous blood (p less than 0.05), while heart rate (p less than 0.001) and cardiac output (p less than 0.05) were increased. Recoveries of heart rate and left ventricular end-diastolic pressure were not shown within 60 min after SNP had been stopped. Both ATP and SNP should act on the pacemaker tissue of the heart.","[{'text': 'hypotension', 'type': 'Disease', 'start': 26, 'end': 37, 'mesh': 'D007022'}, {'text': 'adenosine triphosphate', 'type': 'Chemical', 'start': 49, 'end': 71, 'mesh': 'D000255'}, {'text': 'sodium nitroprusside', 'type': 'Chemical', 'start': 76, 'end': 96, 'mesh': 'D009599'}, {'text': 'Adenosine triphosphate', 'type': 'Chemical', 'start': 129, 'end': 151, 'mesh': 'D000255'}, {'text': 'ATP', 'type': 'Chemical', 'start': 153, 'end': 156, 'mesh': 'D000255'}, {'text': 'sodium nitroprusside', 'type': 'Chemical', 'start': 162, 'end': 182, 'mesh': 'D009599'}, {'text': 'SNP', 'type': 'Chemical', 'start': 184, 'end': 187, 'mesh': 'D009599'}, {'text': 'hypotension', 'type': 'Disease', 'start': 240, 'end': 251, 'mesh': 'D007022'}, {'text': 'SNP', 'type': 'Chemical', 'start': 271, 'end': 274, 'mesh': 'D009599'}, {'text': 'ATP', 'type': 'Chemical', 'start': 325, 'end': 328, 'mesh': 'D000255'}, {'text': 'ATP', 'type': 'Chemical', 'start': 527, 'end': 530, 'mesh': 'D000255'}, {'text': 'SNP', 'type': 'Chemical', 'start': 544, 'end': 547, 'mesh': 'D009599'}, {'text': 'hypotension', 'type': 'Disease', 'start': 667, 'end': 678, 'mesh': 'D007022'}, {'text': 'Hypotension', 'type': 'Disease', 'start': 725, 'end': 736, 'mesh': 'D007022'}, {'text': 'ATP', 'type': 'Chemical', 'start': 748, 'end': 751, 'mesh': 'D000255'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 1059, 'end': 1065, 'mesh': 'D010100'}, {'text': 'ATP', 'type': 'Chemical', 'start': 1190, 'end': 1193, 'mesh': 'D000255'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1245, 'end': 1256, 'mesh': 'D007022'}, {'text': 'SNP', 'type': 'Chemical', 'start': 1269, 'end': 1272, 'mesh': 'D009599'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 1562, 'end': 1568, 'mesh': 'D010100'}, {'text': 'SNP', 'type': 'Chemical', 'start': 1843, 'end': 1846, 'mesh': 'D009599'}, {'text': 'ATP', 'type': 'Chemical', 'start': 1870, 'end': 1873, 'mesh': 'D000255'}, {'text': 'SNP', 'type': 'Chemical', 'start': 1878, 'end': 1881, 'mesh': 'D009599'}]"
+1257,7173007,"Comparative study: Endografine (diatrizoate), Vasurix polyvidone (acetrizoate), Dimer-X (iocarmate) and Hexabrix (ioxaglate) in hysterosalpingography.","Side effects of hysterosalpingography with Dimer-X, Hexabrix, Vasurix polyvidone and Endografine in 142 consecutive patients, receiving one of the four tested media were evaluated from replies to postal questionnaires. The Dimer-X group had a higher incidence of nausea and dizziness. The Endografine group had a higher incidence of abdominal pain. These differences occur especially in the age groups under 30 years. Hexabrix and Vasurix polyvidone are considered the best contrast media for hysterosalpingography and perhaps because of its low toxicity Hexabrix should be preferred.","[{'text': 'Endografine', 'type': 'Chemical', 'start': 19, 'end': 30, 'mesh': 'C006753'}, {'text': 'diatrizoate', 'type': 'Chemical', 'start': 32, 'end': 43, 'mesh': 'D003973'}, {'text': 'Vasurix polyvidone', 'type': 'Chemical', 'start': 46, 'end': 64, 'mesh': 'D000100'}, {'text': 'acetrizoate', 'type': 'Chemical', 'start': 66, 'end': 77, 'mesh': 'D000100'}, {'text': 'Dimer-X', 'type': 'Chemical', 'start': 80, 'end': 87, 'mesh': 'C025504'}, {'text': 'iocarmate', 'type': 'Chemical', 'start': 89, 'end': 98, 'mesh': 'C025504'}, {'text': 'Hexabrix', 'type': 'Chemical', 'start': 104, 'end': 112, 'mesh': 'D007485'}, {'text': 'ioxaglate', 'type': 'Chemical', 'start': 114, 'end': 123, 'mesh': 'D007485'}, {'text': 'Dimer-X', 'type': 'Chemical', 'start': 194, 'end': 201, 'mesh': 'C025504'}, {'text': 'Hexabrix', 'type': 'Chemical', 'start': 203, 'end': 211, 'mesh': 'D007485'}, {'text': 'Vasurix polyvidone', 'type': 'Chemical', 'start': 213, 'end': 231, 'mesh': 'D000100'}, {'text': 'Endografine', 'type': 'Chemical', 'start': 236, 'end': 247, 'mesh': 'C006753'}, {'text': 'Dimer-X', 'type': 'Chemical', 'start': 374, 'end': 381, 'mesh': 'C025504'}, {'text': 'nausea', 'type': 'Disease', 'start': 414, 'end': 420, 'mesh': 'D009325'}, {'text': 'dizziness', 'type': 'Disease', 'start': 425, 'end': 434, 'mesh': 'D004244'}, {'text': 'Endografine', 'type': 'Chemical', 'start': 440, 'end': 451, 'mesh': 'C006753'}, {'text': 'abdominal pain', 'type': 'Disease', 'start': 484, 'end': 498, 'mesh': 'D015746'}, {'text': 'Hexabrix', 'type': 'Chemical', 'start': 569, 'end': 577, 'mesh': 'D007485'}, {'text': 'Vasurix polyvidone', 'type': 'Chemical', 'start': 582, 'end': 600, 'mesh': 'D000100'}, {'text': 'contrast media', 'type': 'Chemical', 'start': 625, 'end': 639, 'mesh': 'D003287'}, {'text': 'toxicity', 'type': 'Disease', 'start': 697, 'end': 705, 'mesh': 'D064420'}, {'text': 'Hexabrix', 'type': 'Chemical', 'start': 706, 'end': 714, 'mesh': 'D007485'}]"
+1258,7176945,Post-suxamethonium pains in Nigerian surgical patients.,"Contrary to an earlier report by Coxon, scoline pain occurs in African negroes. Its incidence was determined in a prospective study involving a total of 100 Nigerian patients (50 out-patients and 50 in-patients). About 62% of the out-patients developed scoline pain as compared with about 26% among the in-patients. The abolition of muscle fasciculations (by 0.075mg/kg dose of Fazadinium) did not influence the occurrence of scoline pain. Neither the type of induction agent (Althesin or Thiopentone) nor the salt preparation of suxamethonium used (chloride or bromide), affected the incidence of scoline pain.","[{'text': 'suxamethonium', 'type': 'Chemical', 'start': 5, 'end': 18, 'mesh': 'D013390'}, {'text': 'pains', 'type': 'Disease', 'start': 19, 'end': 24, 'mesh': 'D010146'}, {'text': 'scoline', 'type': 'Chemical', 'start': 96, 'end': 103, 'mesh': 'D013390'}, {'text': 'pain', 'type': 'Disease', 'start': 104, 'end': 108, 'mesh': 'D010146'}, {'text': 'scoline', 'type': 'Chemical', 'start': 309, 'end': 316, 'mesh': 'D013390'}, {'text': 'pain', 'type': 'Disease', 'start': 317, 'end': 321, 'mesh': 'D010146'}, {'text': 'fasciculations', 'type': 'Disease', 'start': 396, 'end': 410, 'mesh': 'D005207'}, {'text': 'Fazadinium', 'type': 'Chemical', 'start': 434, 'end': 444, 'mesh': 'C084773'}, {'text': 'scoline', 'type': 'Chemical', 'start': 482, 'end': 489, 'mesh': 'D013390'}, {'text': 'pain', 'type': 'Disease', 'start': 490, 'end': 494, 'mesh': 'D010146'}, {'text': 'Althesin', 'type': 'Chemical', 'start': 533, 'end': 541, 'mesh': 'D000530'}, {'text': 'Thiopentone', 'type': 'Chemical', 'start': 545, 'end': 556, 'mesh': 'D013874'}, {'text': 'suxamethonium', 'type': 'Chemical', 'start': 586, 'end': 599, 'mesh': 'D013390'}, {'text': 'chloride', 'type': 'Chemical', 'start': 606, 'end': 614, 'mesh': 'D002712'}, {'text': 'bromide', 'type': 'Chemical', 'start': 618, 'end': 625, 'mesh': 'D001965'}, {'text': 'scoline', 'type': 'Chemical', 'start': 654, 'end': 661, 'mesh': 'D013390'}, {'text': 'pain', 'type': 'Disease', 'start': 662, 'end': 666, 'mesh': 'D010146'}]"
+1259,7315949,Medial changes in arterial spasm induced by L-norepinephrine.,"In normal rats, the media of small arteries (0.4--0.2 mm in diameter) previously was shown to contain intracellular vacuoles, identified ultrastructurally as herniations of one smooth muscle cell into another. The hypothesis that intense vasoconstriction would increase the number of such vacuoles has been tested. In the media of the saphenous artery and its distal branch, vasoconstriction induced by L-norepinephrine produced many cell-to-cell hernias within 15 minutes. At 1 day their number was reduced to about 1/10 of the original number. By 7 days the vessel was almost restored to normal. Triple stimulation over 1 day induced more severe changes in the media. These findings suggest that smooth muscle cells are susceptible to damage in the course of their specific function. The experimental data are discussed in relation to medial changes observed in other instances of arterial spasm. Endothelial changes that developed in the same experimental model were described in a previous paper.","[{'text': 'spasm', 'type': 'Disease', 'start': 27, 'end': 32, 'mesh': 'D013035'}, {'text': 'L-norepinephrine', 'type': 'Chemical', 'start': 44, 'end': 60, 'mesh': 'D009638'}, {'text': 'L-norepinephrine', 'type': 'Chemical', 'start': 465, 'end': 481, 'mesh': 'D009638'}, {'text': 'hernias', 'type': 'Disease', 'start': 509, 'end': 516, 'mesh': 'D006547'}, {'text': 'spasm', 'type': 'Disease', 'start': 954, 'end': 959, 'mesh': 'D013035'}]"
+1260,7369302,Abnormalities of the pupil and visual-evoked potential in quinine amblyopia.,"Total blindness with a transient tonic pupillary response, denervation supersensitivity, and abnormal visual-evoked potentials developed in a 54-year-old man after the use of quinine sulfate for leg cramps. He later recovered normal visual acuity. A transient tonic pupillary response, denervation supersensitivity, and abnormal visual-evoked potentials in quinine toxicity, to our knowledge, have not been previously reported.","[{'text': 'quinine', 'type': 'Chemical', 'start': 58, 'end': 65, 'mesh': 'D011803'}, {'text': 'amblyopia', 'type': 'Disease', 'start': 66, 'end': 75, 'mesh': 'D000550'}, {'text': 'blindness', 'type': 'Disease', 'start': 83, 'end': 92, 'mesh': 'D001766'}, {'text': 'tonic pupillary', 'type': 'Disease', 'start': 110, 'end': 125, 'mesh': 'D015845'}, {'text': 'quinine sulfate', 'type': 'Chemical', 'start': 252, 'end': 267, 'mesh': 'D011803'}, {'text': 'leg cramps', 'type': 'Disease', 'start': 272, 'end': 282, 'mesh': 'D009120'}, {'text': 'tonic pupillary', 'type': 'Disease', 'start': 337, 'end': 352, 'mesh': 'D015845'}, {'text': 'quinine', 'type': 'Chemical', 'start': 434, 'end': 441, 'mesh': 'D011803'}, {'text': 'toxicity', 'type': 'Disease', 'start': 442, 'end': 450, 'mesh': 'D064420'}]"
+1261,7378868,Suxamethonium-induced jaw stiffness and myalgia associated with atypical cholinesterase: case report.,"An 11-year-old boy was given halothane, nitrous oxide and oxygen, pancuronium 0.4 mg and suxamethonium 100 mg for induction of anaesthesia. In response to this a marked jaw stiffness occurred which lasted for two minutes and the anaesthesia were terminated. Four hours of apnoea ensued and he suffered generalized severe myalgia lasting for one week. He was found to have atypical plasma cholinesterase with a dibucaine number of 12, indicating homozygocity. This was verified by study of the family. The case shows that prolonged jaw rigidity and myalgia may occur after suxamethonium in patients with atypical cholinesterase despite pretreatment with pancuronium.","[{'text': 'Suxamethonium', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'D013390'}, {'text': 'jaw stiffness', 'type': 'Disease', 'start': 22, 'end': 35, 'mesh': 'D014313'}, {'text': 'myalgia', 'type': 'Disease', 'start': 40, 'end': 47, 'mesh': 'D063806'}, {'text': 'halothane', 'type': 'Chemical', 'start': 131, 'end': 140, 'mesh': 'D006221'}, {'text': 'nitrous oxide', 'type': 'Chemical', 'start': 142, 'end': 155, 'mesh': 'D009609'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 160, 'end': 166, 'mesh': 'D010100'}, {'text': 'pancuronium', 'type': 'Chemical', 'start': 168, 'end': 179, 'mesh': 'D010197'}, {'text': 'suxamethonium', 'type': 'Chemical', 'start': 191, 'end': 204, 'mesh': 'D013390'}, {'text': 'jaw stiffness', 'type': 'Disease', 'start': 271, 'end': 284, 'mesh': 'D014313'}, {'text': 'apnoea', 'type': 'Disease', 'start': 374, 'end': 380, 'mesh': 'D001049'}, {'text': 'myalgia', 'type': 'Disease', 'start': 423, 'end': 430, 'mesh': 'D063806'}, {'text': 'dibucaine', 'type': 'Chemical', 'start': 512, 'end': 521, 'mesh': 'D003992'}, {'text': 'prolonged jaw rigidity', 'type': 'Disease', 'start': 623, 'end': 645, 'mesh': 'D014313'}, {'text': 'myalgia', 'type': 'Disease', 'start': 650, 'end': 657, 'mesh': 'D063806'}, {'text': 'suxamethonium', 'type': 'Chemical', 'start': 674, 'end': 687, 'mesh': 'D013390'}, {'text': 'pancuronium', 'type': 'Chemical', 'start': 755, 'end': 766, 'mesh': 'D010197'}]"
+1262,7411769,Indomethacin-induced hyperkalemia in three patients with gouty arthritis.,"We describe three patients in whom severe, life-threatening hyperkalemia and renal insufficiency developed after treatment of acute gouty arthritis with indomethacin. This complication may result from an inhibition of prostaglandin synthesis and consequent hyporeninemic hypoaidosteronism. Careful attention to renal function and potassium balance in patients receiving indomethacin or other nonsteroidal anti-inflammatory agents, particularly in those patients with diabetes mellitus or preexisting renal disease, will help prevent this potentially serious complication.","[{'text': 'Indomethacin', 'type': 'Chemical', 'start': 0, 'end': 12, 'mesh': 'D007213'}, {'text': 'hyperkalemia', 'type': 'Disease', 'start': 21, 'end': 33, 'mesh': 'D006947'}, {'text': 'gouty arthritis', 'type': 'Disease', 'start': 57, 'end': 72, 'mesh': 'D015210'}, {'text': 'hyperkalemia', 'type': 'Disease', 'start': 134, 'end': 146, 'mesh': 'D006947'}, {'text': 'renal insufficiency', 'type': 'Disease', 'start': 151, 'end': 170, 'mesh': 'D051437'}, {'text': 'gouty arthritis', 'type': 'Disease', 'start': 206, 'end': 221, 'mesh': 'D015210'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 227, 'end': 239, 'mesh': 'D007213'}, {'text': 'prostaglandin', 'type': 'Chemical', 'start': 292, 'end': 305, 'mesh': 'D011453'}, {'text': 'hyporeninemic hypoaidosteronism', 'type': 'Disease', 'start': 331, 'end': 362, 'mesh': 'D006994'}, {'text': 'potassium', 'type': 'Chemical', 'start': 404, 'end': 413, 'mesh': 'D011188'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 444, 'end': 456, 'mesh': 'D007213'}, {'text': 'diabetes mellitus', 'type': 'Disease', 'start': 541, 'end': 558, 'mesh': 'D003920'}, {'text': 'renal disease', 'type': 'Disease', 'start': 574, 'end': 587, 'mesh': 'D007674'}]"
+1263,7457821,Etomidate: a foreshortened clinical trial.,"A clinical evaluation of etomidate for outpatient cystoscopy was embarked upon. Unpremedicated patients were given fentanyl 1 microgram/kg followed by etomidate 0.3 mg/kg. Anaesthesia was maintained with intermittent etomidate in 2-4 mg doses. Patients were interviewed personally later the same day, and by questionnaire three to four weeks later. The trial was discontinued after 20 cases because of an unacceptable incidence of side effects. Venous pain occurred in 68% of patients and 50% had redness, pain or swelling related to the injection site, in some cases lasting up to three weeks after anaesthesia. Skeletal movements occurred in 50% of patients; 30% experienced respiratory upset, one sufficiently severe to necessitate abandoning the technique. Nausea and vomiting occurred in 40% and 25% had disturbing emergence psychoses.","[{'text': 'Etomidate', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D005045'}, {'text': 'etomidate', 'type': 'Chemical', 'start': 68, 'end': 77, 'mesh': 'D005045'}, {'text': 'fentanyl', 'type': 'Chemical', 'start': 158, 'end': 166, 'mesh': 'D005283'}, {'text': 'etomidate', 'type': 'Chemical', 'start': 194, 'end': 203, 'mesh': 'D005045'}, {'text': 'etomidate', 'type': 'Chemical', 'start': 260, 'end': 269, 'mesh': 'D005045'}, {'text': 'pain', 'type': 'Disease', 'start': 495, 'end': 499, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 549, 'end': 553, 'mesh': 'D010146'}, {'text': 'swelling', 'type': 'Disease', 'start': 557, 'end': 565, 'mesh': 'D004487'}, {'text': 'respiratory upset', 'type': 'Disease', 'start': 720, 'end': 737, 'mesh': 'D012140'}, {'text': 'Nausea', 'type': 'Disease', 'start': 804, 'end': 810, 'mesh': 'D009325'}, {'text': 'vomiting', 'type': 'Disease', 'start': 815, 'end': 823, 'mesh': 'D014839'}, {'text': 'psychoses', 'type': 'Disease', 'start': 873, 'end': 882, 'mesh': 'D011605'}]"
+1264,7477981,Levodopa-induced dyskinesias are improved by fluoxetine.,"We evaluated the severity of motor disability and dyskinesias in seven levodopa-responsive patients with Parkinson's disease after an acute challenge with the mixed dopamine agonist, apomorphine, before and after the administration of fluoxetine (20 mg twice per day) for 11 +/- 1 days. After fluoxetine treatment, there was a significant 47% improvement (p < 0.05) of apomorphine-induced dyskinesias without modification of parkinsonian motor disability. The dyskinesias were reduced predominantly in the lower limbs during the onset and disappearance of dystonic dyskinesias (onset- and end-of-dose dyskinesias) and in the upper limbs during choreic mid-dose dyskinesias. The results suggest that increased brain serotoninergic transmission with fluoxetine may reduce levodopa- or dopamine agonist-induced dyskinesias without aggravating parkinsonian motor disability.","[{'text': 'Levodopa', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 17, 'end': 28, 'mesh': 'D004409'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 45, 'end': 55, 'mesh': 'D005473'}, {'text': 'motor disability', 'type': 'Disease', 'start': 86, 'end': 102, 'mesh': 'D009069'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 107, 'end': 118, 'mesh': 'D004409'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 128, 'end': 136, 'mesh': 'D007980'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 162, 'end': 181, 'mesh': 'D010300'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 222, 'end': 230, 'mesh': 'D004298'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 240, 'end': 251, 'mesh': 'D001058'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 292, 'end': 302, 'mesh': 'D005473'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 350, 'end': 360, 'mesh': 'D005473'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 426, 'end': 437, 'mesh': 'D001058'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 446, 'end': 457, 'mesh': 'D004409'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 482, 'end': 494, 'mesh': 'D010300'}, {'text': 'motor disability', 'type': 'Disease', 'start': 495, 'end': 511, 'mesh': 'D009069'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 517, 'end': 528, 'mesh': 'D004409'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 658, 'end': 669, 'mesh': 'D004409'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 805, 'end': 815, 'mesh': 'D005473'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 827, 'end': 835, 'mesh': 'D007980'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 840, 'end': 848, 'mesh': 'D004298'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 865, 'end': 876, 'mesh': 'D004409'}, {'text': 'parkinsonian', 'type': 'Disease', 'start': 897, 'end': 909, 'mesh': 'D010300'}, {'text': 'motor disability', 'type': 'Disease', 'start': 910, 'end': 926, 'mesh': 'D009069'}]"
+1265,7479194,"A large population-based follow-up study of trimethoprim-sulfamethoxazole, trimethoprim, and cephalexin for uncommon serious drug toxicity.","We conducted a population-based 45-day follow-up study of 232,390 people who were prescribed trimethoprim-sulfamethoxazole (TMP-SMZ), 266,951 prescribed trimethoprim alone, and 196,397 prescribed cephalexin, to estimate the risk of serious liver, blood, skin, and renal disorders resulting in referral or hospitalization associated with these drugs. The results were based on information recorded on office computers by selected general practitioners in the United Kingdom, together with a review of clinical records. The risk of clinically important idiopathic liver disease was similar for persons prescribed TMP-SMZ (5.2/100,000) and those prescribed trimethoprim alone (3.8/100,000). The risk for those prescribed cephalexin was somewhat lower (2.0/100,000). Only five patients experienced blood disorders, one of whom was exposed to TMP-SMZ; of seven with erythema multiforme and Stevens-Johnson syndrome, four were exposed to TMP-SMZ. The one case of toxic epidermal necrolysis occurred in a patient who took cephalexin. Finally, only five cases of acute parenchymal renal disease occurred, none likely to be caused by a study drug. We conclude that the risk of the serious diseases studied is small for the three agents, and compares reasonably with the risk for many other antibiotics.","[{'text': 'trimethoprim-sulfamethoxazole', 'type': 'Chemical', 'start': 44, 'end': 73, 'mesh': 'D015662'}, {'text': 'trimethoprim', 'type': 'Chemical', 'start': 75, 'end': 87, 'mesh': 'D014295'}, {'text': 'cephalexin', 'type': 'Chemical', 'start': 93, 'end': 103, 'mesh': 'D002506'}, {'text': 'drug toxicity', 'type': 'Disease', 'start': 125, 'end': 138, 'mesh': 'D064420'}, {'text': 'trimethoprim-sulfamethoxazole', 'type': 'Chemical', 'start': 233, 'end': 262, 'mesh': 'D015662'}, {'text': 'TMP-SMZ', 'type': 'Chemical', 'start': 264, 'end': 271, 'mesh': 'D015662'}, {'text': 'trimethoprim', 'type': 'Chemical', 'start': 293, 'end': 305, 'mesh': 'D014295'}, {'text': 'cephalexin', 'type': 'Chemical', 'start': 336, 'end': 346, 'mesh': 'D002506'}, {'text': 'liver disease', 'type': 'Disease', 'start': 702, 'end': 715, 'mesh': 'D008107'}, {'text': 'TMP-SMZ', 'type': 'Chemical', 'start': 751, 'end': 758, 'mesh': 'D015662'}, {'text': 'trimethoprim', 'type': 'Chemical', 'start': 794, 'end': 806, 'mesh': 'D014295'}, {'text': 'cephalexin', 'type': 'Chemical', 'start': 858, 'end': 868, 'mesh': 'D002506'}, {'text': 'TMP-SMZ', 'type': 'Chemical', 'start': 978, 'end': 985, 'mesh': 'D015662'}, {'text': 'erythema multiforme', 'type': 'Disease', 'start': 1001, 'end': 1020, 'mesh': 'D004892'}, {'text': 'Stevens-Johnson syndrome', 'type': 'Disease', 'start': 1025, 'end': 1049, 'mesh': 'D013262'}, {'text': 'TMP-SMZ', 'type': 'Chemical', 'start': 1072, 'end': 1079, 'mesh': 'D015662'}, {'text': 'toxic epidermal necrolysis', 'type': 'Disease', 'start': 1097, 'end': 1123, 'mesh': 'D013262'}, {'text': 'cephalexin', 'type': 'Chemical', 'start': 1155, 'end': 1165, 'mesh': 'D002506'}, {'text': 'renal disease', 'type': 'Disease', 'start': 1213, 'end': 1226, 'mesh': 'D007674'}]"
+1266,7492040,Clinical safety of lidocaine in patients with cocaine-associated myocardial infarction.,"STUDY OBJECTIVE: To evaluate the safety of lidocaine in the setting of cocaine-induced myocardial infarction (MI). DESIGN: A retrospective, multicenter study. SETTING: Twenty-nine university, university-affiliated, or community hospitals during a 6-year period (total of 117 cumulative hospital-years). PARTICIPANTS: Patients with cocaine-associated MI who received lidocaine in the emergency department. RESULTS: Of 29 patients who received lidocaine in the setting of cocaine-associated MI, no patient died; exhibited bradydysrhythmias, ventricular tachycardia, or ventricular fibrillation; or experienced seizures after administration of lidocaine (95% confidence interval, 0% to 11%). CONCLUSION: Despite theoretical concerns that lidocaine may enhance cocaine toxicity, the use of lidocaine in patients with cocaine-associated MI was not associated with significant cardiovascular or central nervous system toxicity.","[{'text': 'lidocaine', 'type': 'Chemical', 'start': 19, 'end': 28, 'mesh': 'D008012'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 46, 'end': 53, 'mesh': 'D003042'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 65, 'end': 86, 'mesh': 'D009203'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 131, 'end': 140, 'mesh': 'D008012'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 159, 'end': 166, 'mesh': 'D003042'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 175, 'end': 196, 'mesh': 'D009203'}, {'text': 'MI', 'type': 'Disease', 'start': 198, 'end': 200, 'mesh': 'D009203'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 419, 'end': 426, 'mesh': 'D003042'}, {'text': 'MI', 'type': 'Disease', 'start': 438, 'end': 440, 'mesh': 'D009203'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 454, 'end': 463, 'mesh': 'D008012'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 530, 'end': 539, 'mesh': 'D008012'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 558, 'end': 565, 'mesh': 'D003042'}, {'text': 'MI', 'type': 'Disease', 'start': 577, 'end': 579, 'mesh': 'D009203'}, {'text': 'bradydysrhythmias', 'type': 'Disease', 'start': 608, 'end': 625, 'mesh': 'D001919'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 627, 'end': 650, 'mesh': 'D017180'}, {'text': 'ventricular fibrillation', 'type': 'Disease', 'start': 655, 'end': 679, 'mesh': 'D014693'}, {'text': 'seizures', 'type': 'Disease', 'start': 696, 'end': 704, 'mesh': 'D012640'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 729, 'end': 738, 'mesh': 'D008012'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 823, 'end': 832, 'mesh': 'D008012'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 845, 'end': 852, 'mesh': 'D003042'}, {'text': 'toxicity', 'type': 'Disease', 'start': 853, 'end': 861, 'mesh': 'D064420'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 874, 'end': 883, 'mesh': 'D008012'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 901, 'end': 908, 'mesh': 'D003042'}, {'text': 'MI', 'type': 'Disease', 'start': 920, 'end': 922, 'mesh': 'D009203'}]"
+1267,7644931,Paclitaxel 3-hour infusion given alone and combined with carboplatin: preliminary results of dose-escalation trials.,"Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) by 3-hour infusion was combined with carboplatin in a phase I/II study directed to patients with non-small cell lung cancer. Carboplatin was given at a fixed target area under the concentration-time curve of 6.0 by the Calvert formula, whereas paclitaxel was escalated in patient cohorts from 150 mg/m2 (dose level I) to 175, 200, 225, and 250 mg/m2. The 225 mg/m2 level was expanded for the phase II study since the highest level achieved (250 mg/m2) required modification because of nonhematologic toxicities (arthralgia and sensory neuropathy). Therapeutic effects were noted at all dose levels, with objective responses in 17 (two complete and 15 partial regressions) of 41 previously untreated patients. Toxicities were compared with a cohort of patients in a phase I trial of paclitaxel alone at identical dose levels. Carboplatin did not appear to add to the hematologic toxicities observed, and the paclitaxel/carboplatin combination could be dosed every 3 weeks.","[{'text': 'Paclitaxel', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D017239'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 57, 'end': 68, 'mesh': 'D016190'}, {'text': 'Paclitaxel', 'type': 'Chemical', 'start': 117, 'end': 127, 'mesh': 'D017239'}, {'text': 'Taxol', 'type': 'Chemical', 'start': 129, 'end': 134, 'mesh': 'D017239'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 218, 'end': 229, 'mesh': 'D016190'}, {'text': 'non-small cell lung cancer', 'type': 'Disease', 'start': 278, 'end': 304, 'mesh': 'D002289'}, {'text': 'Carboplatin', 'type': 'Chemical', 'start': 306, 'end': 317, 'mesh': 'D016190'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 425, 'end': 435, 'mesh': 'D017239'}, {'text': 'toxicities', 'type': 'Disease', 'start': 681, 'end': 691, 'mesh': 'D064420'}, {'text': 'arthralgia', 'type': 'Disease', 'start': 693, 'end': 703, 'mesh': 'D018771'}, {'text': 'sensory neuropathy', 'type': 'Disease', 'start': 708, 'end': 726, 'mesh': 'D012678'}, {'text': 'Toxicities', 'type': 'Disease', 'start': 890, 'end': 900, 'mesh': 'D064420'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 963, 'end': 973, 'mesh': 'D017239'}, {'text': 'Carboplatin', 'type': 'Chemical', 'start': 1006, 'end': 1017, 'mesh': 'D016190'}, {'text': 'hematologic toxicities', 'type': 'Disease', 'start': 1047, 'end': 1069, 'mesh': 'D006402'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 1088, 'end': 1098, 'mesh': 'D017239'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 1099, 'end': 1110, 'mesh': 'D016190'}]"
+1268,7661171,The dose-dependent effect of misoprostol on indomethacin-induced renal dysfunction in well compensated cirrhosis.,"Misoprostol (200 micrograms) has been shown to acutely counteract the indomethacin-induced renal dysfunction in well compensated cirrhotic patients. The aim of this study was to determine if the prophylactic value of misoprostol was dose-dependent. Parameters of renal hemodynamics and tubular sodium and water handling were assessed by clearance techniques in 26 well compensated cirrhotic patients before and after an oral combination of 50 mg of indomethacin and various doses of misoprostol. The 200-micrograms dose was able to totally abolish the deleterious renal effects of indomethacin, whereas the 800-micrograms dose resulted in significant worsening of renal hemodynamics and sodium retention. These changes were maximal in the hour immediately after medications and slowly returned toward base-line levels thereafter. These results suggest that the renal protective effects of misoprostol is dose-dependent. However, until this apparent ability of 200 micrograms of misoprostol to prevent the adverse effects of indomethacin on renal function is confirmed with chronic frequent dosing, it would be prudent to avoid nonsteroidal anti-inflammatory therapy in patients with cirrhosis.","[{'text': 'misoprostol', 'type': 'Chemical', 'start': 29, 'end': 40, 'mesh': 'D016595'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 44, 'end': 56, 'mesh': 'D007213'}, {'text': 'renal dysfunction', 'type': 'Disease', 'start': 65, 'end': 82, 'mesh': 'D007674'}, {'text': 'cirrhosis', 'type': 'Disease', 'start': 103, 'end': 112, 'mesh': 'D005355'}, {'text': 'Misoprostol', 'type': 'Chemical', 'start': 114, 'end': 125, 'mesh': 'D016595'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 184, 'end': 196, 'mesh': 'D007213'}, {'text': 'renal dysfunction', 'type': 'Disease', 'start': 205, 'end': 222, 'mesh': 'D007674'}, {'text': 'cirrhotic', 'type': 'Disease', 'start': 243, 'end': 252, 'mesh': 'D005355'}, {'text': 'misoprostol', 'type': 'Chemical', 'start': 331, 'end': 342, 'mesh': 'D016595'}, {'text': 'sodium', 'type': 'Chemical', 'start': 408, 'end': 414, 'mesh': 'D012964'}, {'text': 'cirrhotic', 'type': 'Disease', 'start': 495, 'end': 504, 'mesh': 'D005355'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 563, 'end': 575, 'mesh': 'D007213'}, {'text': 'misoprostol', 'type': 'Chemical', 'start': 597, 'end': 608, 'mesh': 'D016595'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 695, 'end': 707, 'mesh': 'D007213'}, {'text': 'sodium', 'type': 'Chemical', 'start': 801, 'end': 807, 'mesh': 'D012964'}, {'text': 'misoprostol', 'type': 'Chemical', 'start': 1003, 'end': 1014, 'mesh': 'D016595'}, {'text': 'misoprostol', 'type': 'Chemical', 'start': 1092, 'end': 1103, 'mesh': 'D016595'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 1138, 'end': 1150, 'mesh': 'D007213'}, {'text': 'cirrhosis', 'type': 'Disease', 'start': 1297, 'end': 1306, 'mesh': 'D005355'}]"
+1269,7671401,Increased frequency and severity of angio-oedema related to long-term therapy with angiotensin-converting enzyme inhibitor in two patients.,"Adverse reactions to drugs are well recognized as a cause of acute or chronic urticaria, and angio-oedema. Angiotensin-converting enzyme (ACE) inhibitors, used to treat hypertension and congestive heart failure, were introduced in Europe in the middle of the eighties, and the use of these drugs has increased progressively. Soon after the introduction of ACE inhibitors, acute bouts of angio-oedema were reported in association with the use of these drugs. We wish to draw attention to the possibility of adverse reactions to ACE inhibitors after long-term use and in patients with pre-existing angio-oedema.","[{'text': 'angio-oedema', 'type': 'Disease', 'start': 36, 'end': 48, 'mesh': 'D000799'}, {'text': 'angiotensin-converting enzyme inhibitor', 'type': 'Chemical', 'start': 83, 'end': 122, 'mesh': 'D000806'}, {'text': 'urticaria', 'type': 'Disease', 'start': 218, 'end': 227, 'mesh': 'D014581'}, {'text': 'angio-oedema', 'type': 'Disease', 'start': 233, 'end': 245, 'mesh': 'D000799'}, {'text': 'Angiotensin-converting enzyme (ACE) inhibitors', 'type': 'Chemical', 'start': 247, 'end': 293, 'mesh': 'D000806'}, {'text': 'hypertension', 'type': 'Disease', 'start': 309, 'end': 321, 'mesh': 'D006973'}, {'text': 'congestive heart failure', 'type': 'Disease', 'start': 326, 'end': 350, 'mesh': 'D006333'}, {'text': 'ACE inhibitors', 'type': 'Chemical', 'start': 496, 'end': 510, 'mesh': 'D000806'}, {'text': 'angio-oedema', 'type': 'Disease', 'start': 527, 'end': 539, 'mesh': 'D000799'}, {'text': 'ACE inhibitors', 'type': 'Chemical', 'start': 667, 'end': 681, 'mesh': 'D000806'}, {'text': 'angio-oedema', 'type': 'Disease', 'start': 736, 'end': 748, 'mesh': 'D000799'}]"
+1270,7727612,Myoclonus associated with lorazepam therapy in very-low-birth-weight infants.,"Lorazepam is being used with increasing frequency as a sedative in the newborn and the young infant. Concern has been raised with regard to the safety of lorazepam in this age group, especially in very-low-birth-weight (VLBW; < 1,500 g) infants. Three young infants, all of birth weight < 1,500 g, experienced myoclonus following the intravenous administration of lorazepam. The potential neurotoxic effects of the drug (and its vehicle) in this population are discussed. Injectable lorazepam should be used with caution in VLBW infants.","[{'text': 'Myoclonus', 'type': 'Disease', 'start': 0, 'end': 9, 'mesh': 'D009207'}, {'text': 'lorazepam', 'type': 'Chemical', 'start': 26, 'end': 35, 'mesh': 'D008140'}, {'text': 'Lorazepam', 'type': 'Chemical', 'start': 78, 'end': 87, 'mesh': 'D008140'}, {'text': 'lorazepam', 'type': 'Chemical', 'start': 232, 'end': 241, 'mesh': 'D008140'}, {'text': 'myoclonus', 'type': 'Disease', 'start': 388, 'end': 397, 'mesh': 'D009207'}, {'text': 'lorazepam', 'type': 'Chemical', 'start': 442, 'end': 451, 'mesh': 'D008140'}, {'text': 'neurotoxic', 'type': 'Disease', 'start': 467, 'end': 477, 'mesh': 'D020258'}, {'text': 'lorazepam', 'type': 'Chemical', 'start': 561, 'end': 570, 'mesh': 'D008140'}]"
+1271,7739955,Transvenous right ventricular pacing during cardiopulmonary resuscitation of pediatric patients with acute cardiomyopathy.,"We describe the cardiopulmonary resuscitation efforts on five patients who presented in acute circulatory failure from myocardial dysfunction. Three patients had acute viral myocarditis, one had a carbamazepine-induced acute eosinophilic myocarditis, and one had cardiac hemosiderosis resulting in acute cardiogenic shock. All patients were continuously monitored with central venous and arterial catheters in addition to routine noninvasive monitoring. An introducer sheath, a pacemaker, and sterile pacing wires were made readily available for the patients, should the need arise to terminate resistant cardiac dysrhythmias. All patients developed cardiocirculatory arrest associated with extreme hypotension and dysrhythmias within the first 48 hours of their admission to the pediatric intensive care unit (PICU). Right ventricular pacemaker wires were inserted in all of them during cardiopulmonary resuscitation (CPR). In four patients, cardiac pacing was used, resulting in a temporary captured rhythm and restoration of their cardiac output. These patients had a second event of cardiac arrest, resulting in death, within 10 to 60 minutes. In one patient, cardiac pacing was not used, because he converted to normal sinus rhythm by electrical defibrillation within three minutes of initiating CPR. We conclude that cardiac pacing during resuscitative efforts in pediatric patients suffering from acute myocardial dysfunction may not have long-term value in and of itself; however, if temporary hemodynamic stability is achieved by this procedure, it may provide additional time needed to institute other therapeutic modalities.","[{'text': 'cardiomyopathy', 'type': 'Disease', 'start': 107, 'end': 121, 'mesh': 'D009202'}, {'text': 'circulatory failure', 'type': 'Disease', 'start': 217, 'end': 236, 'mesh': 'D012769'}, {'text': 'myocardial dysfunction', 'type': 'Disease', 'start': 242, 'end': 264, 'mesh': 'D009202'}, {'text': 'myocarditis', 'type': 'Disease', 'start': 297, 'end': 308, 'mesh': 'D009205'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 320, 'end': 333, 'mesh': 'D002220'}, {'text': 'cardiogenic shock', 'type': 'Disease', 'start': 427, 'end': 444, 'mesh': 'D012770'}, {'text': 'dysrhythmias', 'type': 'Disease', 'start': 736, 'end': 748, 'mesh': 'D001145'}, {'text': 'hypotension', 'type': 'Disease', 'start': 822, 'end': 833, 'mesh': 'D007022'}, {'text': 'dysrhythmias', 'type': 'Disease', 'start': 838, 'end': 850, 'mesh': 'D001145'}, {'text': 'cardiac arrest', 'type': 'Disease', 'start': 1210, 'end': 1224, 'mesh': 'D006323'}, {'text': 'myocardial dysfunction', 'type': 'Disease', 'start': 1533, 'end': 1555, 'mesh': 'D009202'}]"
+1272,7931490,"Efficacy and safety of granisetron, a selective 5-hydroxytryptamine-3 receptor antagonist, in the prevention of nausea and vomiting induced by high-dose cisplatin.","PURPOSE: To assess the antiemetic effects and safety profile of four different doses of granisetron (Kytril; SmithKline Beecham Pharmaceuticals, Philadelphia, PA) when administered as a single intravenous (IV) dose for prophylaxis of cisplatin-induced nausea and vomiting. PATIENTS AND METHODS: One hundred eighty-four chemotherapy-naive patients receiving high-dose cisplatin (81 to 120 mg/m2) were randomized to receive one of four granisetron doses (5, 10, 20, or 40 micrograms/kg) administered before chemotherapy. Patients were observed on an inpatient basis for 18 to 24 hours, and vital signs, nausea, vomiting, retching, and appetite were assessed. Safety analyses included incidence of adverse experiences and laboratory parameter changes. RESULTS: After granisetron doses of 5, 10, 20, and 40 micrograms/kg, a major response (< or = two vomiting or retching episodes, and no antiemetic rescue) was recorded in 23%, 57%, 58%, and 60% of patients, respectively, and a complete response (no vomiting or retching, and no antiemetic rescue) in 18%, 41%, 40%, and 47% of patients, respectively. There was a statistically longer time to first episode of nausea (P = .0015) and vomiting (P = .0001), and fewer patients were administered additional antiemetic medication in the 10-micrograms/kg dosing groups than in the 5-micrograms/kg dosing group. As granisetron dose increased, appetite return increased (P = .040). Headache was the most frequently reported adverse event (20%). CONCLUSION: A single 10-, 20-, or 40-micrograms/kg dose of granisetron was effective in controlling vomiting in 57% to 60% of patients who received cisplatin at doses greater than 81 mg/m2 and totally prevented vomiting in 40% to 47% of patients. There were no statistically significant differences in efficacy between the 10-micrograms/kg dose and the 20- and 40-micrograms/kg doses. Granisetron was well tolerated at all doses.","[{'text': 'granisetron', 'type': 'Chemical', 'start': 23, 'end': 34, 'mesh': 'D017829'}, {'text': '5-hydroxytryptamine', 'type': 'Chemical', 'start': 48, 'end': 67, 'mesh': 'D012701'}, {'text': 'nausea', 'type': 'Disease', 'start': 112, 'end': 118, 'mesh': 'D009325'}, {'text': 'vomiting', 'type': 'Disease', 'start': 123, 'end': 131, 'mesh': 'D014839'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 153, 'end': 162, 'mesh': 'D002945'}, {'text': 'granisetron', 'type': 'Chemical', 'start': 252, 'end': 263, 'mesh': 'D017829'}, {'text': 'Kytril', 'type': 'Chemical', 'start': 265, 'end': 271, 'mesh': 'D017829'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 398, 'end': 407, 'mesh': 'D002945'}, {'text': 'nausea', 'type': 'Disease', 'start': 416, 'end': 422, 'mesh': 'D009325'}, {'text': 'vomiting', 'type': 'Disease', 'start': 427, 'end': 435, 'mesh': 'D014839'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 531, 'end': 540, 'mesh': 'D002945'}, {'text': 'granisetron', 'type': 'Chemical', 'start': 598, 'end': 609, 'mesh': 'D017829'}, {'text': 'nausea', 'type': 'Disease', 'start': 765, 'end': 771, 'mesh': 'D009325'}, {'text': 'vomiting', 'type': 'Disease', 'start': 773, 'end': 781, 'mesh': 'D014839'}, {'text': 'granisetron', 'type': 'Chemical', 'start': 928, 'end': 939, 'mesh': 'D017829'}, {'text': 'vomiting', 'type': 'Disease', 'start': 1011, 'end': 1019, 'mesh': 'D014839'}, {'text': 'vomiting', 'type': 'Disease', 'start': 1162, 'end': 1170, 'mesh': 'D014839'}, {'text': 'nausea', 'type': 'Disease', 'start': 1321, 'end': 1327, 'mesh': 'D009325'}, {'text': 'vomiting', 'type': 'Disease', 'start': 1344, 'end': 1352, 'mesh': 'D014839'}, {'text': 'granisetron', 'type': 'Chemical', 'start': 1519, 'end': 1530, 'mesh': 'D017829'}, {'text': 'Headache', 'type': 'Disease', 'start': 1585, 'end': 1593, 'mesh': 'D006261'}, {'text': 'granisetron', 'type': 'Chemical', 'start': 1707, 'end': 1718, 'mesh': 'D017829'}, {'text': 'vomiting', 'type': 'Disease', 'start': 1748, 'end': 1756, 'mesh': 'D014839'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 1796, 'end': 1805, 'mesh': 'D002945'}, {'text': 'vomiting', 'type': 'Disease', 'start': 1859, 'end': 1867, 'mesh': 'D014839'}, {'text': 'Granisetron', 'type': 'Chemical', 'start': 2033, 'end': 2044, 'mesh': 'D017829'}]"
+1273,7949506,Adverse interaction between clonidine and verapamil.,"OBJECTIVE: To report two cases of a possible adverse interaction between clonidine and verapamil resulting in atrioventricular (AV) block in both patients and severe hypotension in one patient. CASE SUMMARIES: A 54-year-old woman with hyperaldosteronism was treated with verapamil 480 mg/d and spironolactone 100 mg/d. After the addition of a minimal dose of clonidine (0.15 mg bid), she developed complete AV block and severe hypotension, which resolved upon cessation of all medications. A 65-year-old woman was treated with extended-release verapamil 240 mg/d. After the addition of clonidine 0.15 mg bid she developed complete AV block, which resolved after all therapy was stopped. DISCUSSION: An adverse interaction between clonidine and verapamil has not been reported previously. We describe two such cases and discuss the various mechanisms that might cause such an interaction. Clinicians should be acquainted with this possibly fatal interaction between two commonly used antihypertensive drugs. CONCLUSIONS: Caution is recommended in combining clonidine and verapamil therapy, even in patients who do not have sinus or AV node dysfunction. The two drugs may act synergistically on both the AV node and the peripheral circulation.","[{'text': 'clonidine', 'type': 'Chemical', 'start': 28, 'end': 37, 'mesh': 'D003000'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 42, 'end': 51, 'mesh': 'D014700'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 126, 'end': 135, 'mesh': 'D003000'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 140, 'end': 149, 'mesh': 'D014700'}, {'text': 'atrioventricular (AV) block', 'type': 'Disease', 'start': 163, 'end': 190, 'mesh': 'D054537'}, {'text': 'hypotension', 'type': 'Disease', 'start': 219, 'end': 230, 'mesh': 'D007022'}, {'text': 'hyperaldosteronism', 'type': 'Disease', 'start': 288, 'end': 306, 'mesh': 'D006929'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 324, 'end': 333, 'mesh': 'D014700'}, {'text': 'spironolactone', 'type': 'Chemical', 'start': 347, 'end': 361, 'mesh': 'D013148'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 412, 'end': 421, 'mesh': 'D003000'}, {'text': 'AV block', 'type': 'Disease', 'start': 460, 'end': 468, 'mesh': 'D054537'}, {'text': 'hypotension', 'type': 'Disease', 'start': 480, 'end': 491, 'mesh': 'D007022'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 597, 'end': 606, 'mesh': 'D014700'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 639, 'end': 648, 'mesh': 'D003000'}, {'text': 'AV block', 'type': 'Disease', 'start': 684, 'end': 692, 'mesh': 'D054537'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 783, 'end': 792, 'mesh': 'D003000'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 797, 'end': 806, 'mesh': 'D014700'}, {'text': 'clonidine', 'type': 'Chemical', 'start': 1109, 'end': 1118, 'mesh': 'D003000'}, {'text': 'verapamil', 'type': 'Chemical', 'start': 1123, 'end': 1132, 'mesh': 'D014700'}]"
+1274,7967231,"Pharmacological studies on a new dihydrothienopyridine calcium antagonist, S-312-d. 5th communication: anticonvulsant effects in mice.","S-312, S-312-d, but not S-312-l, L-type calcium channel antagonists, showed anticonvulsant effects on the audiogenic tonic convulsions in DBA/2 mice; and their ED50 values were 18.4 (12.8-27.1) mg/kg, p.o. and 15.0 (10.2-23.7) mg/kg, p.o., respectively, while that of flunarizine was 34.0 (26.0-44.8) mg/kg, p.o. Although moderate anticonvulsant effects of S-312-d in higher doses were observed against the clonic convulsions induced by pentylenetetrazole (85 mg/kg, s.c.) or bemegride (40 mg/kg, s.c.), no effects were observed in convulsions induced by N-methyl-D-aspartate, picrotoxin, or electroshock in Slc:ddY mice. S-312-d may be useful in the therapy of certain types of human epilepsy.","[{'text': 'dihydrothienopyridine calcium', 'type': 'Chemical', 'start': 33, 'end': 62, 'mesh': '-1'}, {'text': 'S-312-d', 'type': 'Chemical', 'start': 75, 'end': 82, 'mesh': 'C059447'}, {'text': 'S-312', 'type': 'Chemical', 'start': 135, 'end': 140, 'mesh': 'C059447'}, {'text': 'S-312-d', 'type': 'Chemical', 'start': 142, 'end': 149, 'mesh': 'C059447'}, {'text': 'S-312-l', 'type': 'Chemical', 'start': 159, 'end': 166, 'mesh': '-1'}, {'text': 'calcium', 'type': 'Chemical', 'start': 175, 'end': 182, 'mesh': 'D002118'}, {'text': 'audiogenic tonic convulsions', 'type': 'Disease', 'start': 241, 'end': 269, 'mesh': 'D020195'}, {'text': 'flunarizine', 'type': 'Chemical', 'start': 403, 'end': 414, 'mesh': 'D005444'}, {'text': 'S-312-d', 'type': 'Chemical', 'start': 492, 'end': 499, 'mesh': 'C059447'}, {'text': 'convulsions', 'type': 'Disease', 'start': 549, 'end': 560, 'mesh': 'D012640'}, {'text': 'pentylenetetrazole', 'type': 'Chemical', 'start': 572, 'end': 590, 'mesh': 'D010433'}, {'text': 'bemegride', 'type': 'Chemical', 'start': 611, 'end': 620, 'mesh': 'D001534'}, {'text': 'convulsions', 'type': 'Disease', 'start': 667, 'end': 678, 'mesh': 'D012640'}, {'text': 'N-methyl-D-aspartate', 'type': 'Chemical', 'start': 690, 'end': 710, 'mesh': 'D016202'}, {'text': 'picrotoxin', 'type': 'Chemical', 'start': 712, 'end': 722, 'mesh': 'D010852'}, {'text': 'S-312-d', 'type': 'Chemical', 'start': 757, 'end': 764, 'mesh': 'C059447'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 820, 'end': 828, 'mesh': 'D004827'}]"
+1275,8096565,Transmural myocardial infarction with sumatriptan.,"For sumatriptan, tightness in the chest caused by an unknown mechanism has been reported in 3-5% of users. We describe a 47-year-old woman with an acute myocardial infarction after administration of sumatriptan 6 mg subcutaneously for cluster headache. The patient had no history of underlying ischaemic heart disease or Prinzmetal's angina. She recovered without complications.","[{'text': 'myocardial infarction', 'type': 'Disease', 'start': 11, 'end': 32, 'mesh': 'D009203'}, {'text': 'sumatriptan', 'type': 'Chemical', 'start': 38, 'end': 49, 'mesh': 'D018170'}, {'text': 'sumatriptan', 'type': 'Chemical', 'start': 55, 'end': 66, 'mesh': 'D018170'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 204, 'end': 225, 'mesh': 'D009203'}, {'text': 'sumatriptan', 'type': 'Chemical', 'start': 250, 'end': 261, 'mesh': 'D018170'}, {'text': 'cluster headache', 'type': 'Disease', 'start': 286, 'end': 302, 'mesh': 'D003027'}, {'text': 'ischaemic heart disease', 'type': 'Disease', 'start': 345, 'end': 368, 'mesh': 'D017202'}, {'text': ""Prinzmetal's angina"", 'type': 'Disease', 'start': 372, 'end': 391, 'mesh': 'D000788'}]"
+1276,8135424,Flumazenil induces seizures and death in mixed cocaine-diazepam intoxications.,"STUDY HYPOTHESIS: Administration of the benzodiazepine antagonist flumazenil may unmask seizures in mixed cocaine-benzodiazepine intoxication. DESIGN: Male Sprague-Dawley rats received 100 mg/kg cocaine IP alone, 5 mg/kg diazepam alone, or a combination of diazepam and cocaine. Three minutes later, groups were challenged with vehicle or flumazenil 5 or 10 mg/kg IP. Animal behavior, seizures (time to and incidence), death (time to and incidence), and cortical EEG tracings were recorded. INTERVENTIONS: Administration of flumazenil to animals after they had received a combination dose of cocaine and diazepam. RESULTS: In group 1, animals received cocaine followed by vehicle. This resulted in 100% developing seizures and death. Group 2 received diazepam alone followed by vehicle. Animals became somnolent and none died. Group 3 received diazepam followed by 5 mg/kg flumazenil. Animals became somnolent after diazepam and then active after flumazenil administration. In group 4, a combination of cocaine and diazepam was administered simultaneously. This resulted in no overt or EEG-detectable seizures and a 50% incidence of death. Group 5 received a similar combination of cocaine and diazepam, followed later by 5 mg/kg flumazenil. This resulted in an increased incidence of seizures, 90% (P < .01), and death, 100% (P < or = .01), compared with group 4. Group 6 received cocaine and diazepam followed by 10 mg/kg flumazenil. This also resulted in an increased incidence of seizures, 90% (P < or = .01), and death, 90% (P < or = .05), compared with group 4. CONCLUSION: Flumazenil can unmask seizures and increase the incidence of death in a model of combined cocaine-diazepam intoxications.","[{'text': 'Flumazenil', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D005442'}, {'text': 'seizures', 'type': 'Disease', 'start': 19, 'end': 27, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 47, 'end': 54, 'mesh': 'D003042'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 55, 'end': 63, 'mesh': 'D003975'}, {'text': 'benzodiazepine', 'type': 'Chemical', 'start': 119, 'end': 133, 'mesh': 'D001569'}, {'text': 'flumazenil', 'type': 'Chemical', 'start': 145, 'end': 155, 'mesh': 'D005442'}, {'text': 'seizures', 'type': 'Disease', 'start': 167, 'end': 175, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 185, 'end': 192, 'mesh': 'D003042'}, {'text': 'benzodiazepine', 'type': 'Chemical', 'start': 193, 'end': 207, 'mesh': 'D001569'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 274, 'end': 281, 'mesh': 'D003042'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 300, 'end': 308, 'mesh': 'D003975'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 336, 'end': 344, 'mesh': 'D003975'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 349, 'end': 356, 'mesh': 'D003042'}, {'text': 'flumazenil', 'type': 'Chemical', 'start': 418, 'end': 428, 'mesh': 'D005442'}, {'text': 'seizures', 'type': 'Disease', 'start': 464, 'end': 472, 'mesh': 'D012640'}, {'text': 'flumazenil', 'type': 'Chemical', 'start': 603, 'end': 613, 'mesh': 'D005442'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 671, 'end': 678, 'mesh': 'D003042'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 683, 'end': 691, 'mesh': 'D003975'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 731, 'end': 738, 'mesh': 'D003042'}, {'text': 'seizures', 'type': 'Disease', 'start': 793, 'end': 801, 'mesh': 'D012640'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 830, 'end': 838, 'mesh': 'D003975'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 923, 'end': 931, 'mesh': 'D003975'}, {'text': 'flumazenil', 'type': 'Chemical', 'start': 952, 'end': 962, 'mesh': 'D005442'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 995, 'end': 1003, 'mesh': 'D003975'}, {'text': 'flumazenil', 'type': 'Chemical', 'start': 1026, 'end': 1036, 'mesh': 'D005442'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1082, 'end': 1089, 'mesh': 'D003042'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 1094, 'end': 1102, 'mesh': 'D003975'}, {'text': 'seizures', 'type': 'Disease', 'start': 1180, 'end': 1188, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1261, 'end': 1268, 'mesh': 'D003042'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 1273, 'end': 1281, 'mesh': 'D003975'}, {'text': 'flumazenil', 'type': 'Chemical', 'start': 1309, 'end': 1319, 'mesh': 'D005442'}, {'text': 'seizures', 'type': 'Disease', 'start': 1364, 'end': 1372, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1461, 'end': 1468, 'mesh': 'D003042'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 1473, 'end': 1481, 'mesh': 'D003975'}, {'text': 'flumazenil', 'type': 'Chemical', 'start': 1503, 'end': 1513, 'mesh': 'D005442'}, {'text': 'seizures', 'type': 'Disease', 'start': 1563, 'end': 1571, 'mesh': 'D012640'}, {'text': 'Flumazenil', 'type': 'Chemical', 'start': 1659, 'end': 1669, 'mesh': 'D005442'}, {'text': 'seizures', 'type': 'Disease', 'start': 1681, 'end': 1689, 'mesh': 'D012640'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1749, 'end': 1756, 'mesh': 'D003042'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 1757, 'end': 1765, 'mesh': 'D003975'}]"
+1277,8160791,Mechanisms for protective effects of free radical scavengers on gentamicin-mediated nephropathy in rats.,"Studies were performed to examine the mechanisms for the protective effects of free radical scavengers on gentamicin (GM)-mediated nephropathy. Administration of GM at 40 mg/kg sc for 13 days to rats induced a significant reduction in renal blood flow (RBF) and inulin clearance (CIn) as well as marked tubular damage. A significant reduction in urinary guanosine 3',5'-cyclic monophosphate (cGMP) excretion and a significant increase in renal cortical renin and endothelin-1 contents were also observed in GM-mediated nephropathy. Superoxide dismutase (SOD) or dimethylthiourea (DMTU) significantly lessened the GM-induced decrement in CIn. The SOD-induced increase in glomerular filtration rate was associated with a marked improvement in RBF, an increase in urinary cGMP excretion, and a decrease in renal renin and endothelin-1 content. SOD did not attenuate the tubular damage. In contrast, DMTU significantly reduced the tubular damage and lipid peroxidation, but it did not affect renal hemodynamics and vasoactive substances. Neither SOD nor DMTU affected the renal cortical GM content in GM-treated rats. These results suggest that 1) both SOD and DMTU have protective effects on GM-mediated nephropathy, 2) the mechanisms for the protective effects differ for SOD and DMTU, and 3) superoxide anions play a critical role in GM-induced renal vasoconstriction.","[{'text': 'gentamicin', 'type': 'Chemical', 'start': 64, 'end': 74, 'mesh': 'D005839'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 84, 'end': 95, 'mesh': 'D007674'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 211, 'end': 221, 'mesh': 'D005839'}, {'text': 'GM', 'type': 'Chemical', 'start': 223, 'end': 225, 'mesh': 'D005839'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 236, 'end': 247, 'mesh': 'D007674'}, {'text': 'GM', 'type': 'Chemical', 'start': 267, 'end': 269, 'mesh': 'D005839'}, {'text': 'tubular damage', 'type': 'Disease', 'start': 408, 'end': 422, 'mesh': 'D007674'}, {'text': ""guanosine 3',5'-cyclic monophosphate"", 'type': 'Chemical', 'start': 459, 'end': 495, 'mesh': 'D006152'}, {'text': 'cGMP', 'type': 'Chemical', 'start': 497, 'end': 501, 'mesh': 'D006152'}, {'text': 'GM', 'type': 'Chemical', 'start': 612, 'end': 614, 'mesh': 'D005839'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 624, 'end': 635, 'mesh': 'D007674'}, {'text': 'Superoxide', 'type': 'Chemical', 'start': 637, 'end': 647, 'mesh': 'D013481'}, {'text': 'dimethylthiourea', 'type': 'Chemical', 'start': 667, 'end': 683, 'mesh': 'C038983'}, {'text': 'DMTU', 'type': 'Chemical', 'start': 685, 'end': 689, 'mesh': 'C038983'}, {'text': 'GM', 'type': 'Chemical', 'start': 718, 'end': 720, 'mesh': 'D005839'}, {'text': 'cGMP', 'type': 'Chemical', 'start': 874, 'end': 878, 'mesh': 'D006152'}, {'text': 'tubular damage', 'type': 'Disease', 'start': 972, 'end': 986, 'mesh': 'D007674'}, {'text': 'DMTU', 'type': 'Chemical', 'start': 1001, 'end': 1005, 'mesh': 'C038983'}, {'text': 'tubular damage', 'type': 'Disease', 'start': 1032, 'end': 1046, 'mesh': 'D007674'}, {'text': 'DMTU', 'type': 'Chemical', 'start': 1155, 'end': 1159, 'mesh': 'C038983'}, {'text': 'GM', 'type': 'Chemical', 'start': 1188, 'end': 1190, 'mesh': 'D005839'}, {'text': 'GM', 'type': 'Chemical', 'start': 1202, 'end': 1204, 'mesh': 'D005839'}, {'text': 'DMTU', 'type': 'Chemical', 'start': 1262, 'end': 1266, 'mesh': 'C038983'}, {'text': 'GM', 'type': 'Chemical', 'start': 1294, 'end': 1296, 'mesh': 'D005839'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1306, 'end': 1317, 'mesh': 'D007674'}, {'text': 'DMTU', 'type': 'Chemical', 'start': 1383, 'end': 1387, 'mesh': 'C038983'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 1396, 'end': 1406, 'mesh': 'D013481'}, {'text': 'GM', 'type': 'Chemical', 'start': 1438, 'end': 1440, 'mesh': 'D005839'}]"
+1278,8184922,Assessment of cardiomyocyte DNA synthesis during hypertrophy in adult mice.,"The ability of cardiomyocytes to synthesize DNA in response to experimentally induced cardiac hypertrophy was assessed in adult mice. Isoproterenol delivered by osmotic minipump implantation in adult C3Heb/FeJ mice resulted in a 46% increase in heart weight and a 19.3% increase in cardiomyocyte area. No DNA synthesis, as assessed by autoradiographic analysis of isolated cardiomyocytes, was observed in control or hypertrophic hearts. A survey of 15 independent inbred strains of mice revealed that ventricular cardiomyocyte nuclear number ranged from 3 to 13% mononucleate, suggesting that cardiomyocyte terminal differentiation is influenced directly or indirectly by genetic background. To determine whether the capacity for reactive DNA synthesis was also subject to genetic regulation, cardiac hypertrophy was induced in the strains of mice comprising the extremes of the nuclear number survey. These data indicate that adult mouse atrial and ventricular cardiomyocytes do not synthesize DNA in response to isoproterenol-induced cardiac hypertrophy.","[{'text': 'hypertrophy', 'type': 'Disease', 'start': 49, 'end': 60, 'mesh': 'D006984'}, {'text': 'cardiac hypertrophy', 'type': 'Disease', 'start': 162, 'end': 181, 'mesh': 'D006332'}, {'text': 'Isoproterenol', 'type': 'Chemical', 'start': 210, 'end': 223, 'mesh': 'D007545'}, {'text': 'hypertrophic hearts', 'type': 'Disease', 'start': 492, 'end': 511, 'mesh': 'D006332'}, {'text': 'cardiac hypertrophy', 'type': 'Disease', 'start': 869, 'end': 888, 'mesh': 'D006332'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1090, 'end': 1103, 'mesh': 'D007545'}, {'text': 'cardiac hypertrophy', 'type': 'Disease', 'start': 1112, 'end': 1131, 'mesh': 'D006332'}]"
+1279,8188982,Central cardiovascular effects of AVP and ANP in normotensive and spontaneously hypertensive rats.,"The purpose of the present study was to compare influence of central arginine vasopressin (AVP) and of atrial natriuretic peptide (ANP) on control of arterial blood pressure (MAP) and heart rate (HR) in normotensive (WKY) and spontaneously hypertensive (SHR) rats. Three series of experiments were performed on 30 WKY and 30 SHR, chronically instrumented with guide tubes in the lateral ventricle (LV) and arterial and venous catheters. MAP and HR were monitored before and after i.v. injections of either vehicle or 1, 10 and 50 ng of AVP and 25, 125 and 500 ng of ANP. Sensitivity of cardiac component of baroreflex (CCB), expressed as a slope of the regression line was determined from relationships between systolic arterial pressure (SAP) and HR period (HRp) during phenylephrine (Phe)-induced hypertension and sodium nitroprusside (SN)-induced hypotension. CCB was measured before and after administration of either vehicle, AVP, ANP, or both peptides together. Increases of MAP occurred after LV administration of 1, 10 and 50 ng of AVP in WKY and of 10 and 50 ng in SHR. ANP did not cause significant changes in MAP in both strains as compared to vehicle, but it abolished AVP-induced MAP increase in WKY and SHR. CCB was reduced in WKY and SHR after LV administration of AVP during SN-induced hypotension. In SHR but not in WKY administration of ANP, AVP and ANP + AVP decreased CCB during Phe-induced MAP elevation. The results indicate that centrally applied AVP and ANP exert differential effects on blood pressure and baroreflex control of heart rate in WKY and SHR and suggest interaction of these two peptides in blood pressure regulation at the level of central nervous system.","[{'text': 'AVP', 'type': 'Chemical', 'start': 34, 'end': 37, 'mesh': 'D001127'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 80, 'end': 92, 'mesh': 'D006973'}, {'text': 'arginine vasopressin', 'type': 'Chemical', 'start': 168, 'end': 188, 'mesh': 'D001127'}, {'text': 'AVP', 'type': 'Chemical', 'start': 190, 'end': 193, 'mesh': 'D001127'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 339, 'end': 351, 'mesh': 'D006973'}, {'text': 'AVP', 'type': 'Chemical', 'start': 635, 'end': 638, 'mesh': 'D001127'}, {'text': 'phenylephrine', 'type': 'Chemical', 'start': 870, 'end': 883, 'mesh': 'D010656'}, {'text': 'Phe', 'type': 'Chemical', 'start': 885, 'end': 888, 'mesh': 'D010656'}, {'text': 'hypertension', 'type': 'Disease', 'start': 898, 'end': 910, 'mesh': 'D006973'}, {'text': 'sodium nitroprusside', 'type': 'Chemical', 'start': 915, 'end': 935, 'mesh': 'D009599'}, {'text': 'SN', 'type': 'Chemical', 'start': 937, 'end': 939, 'mesh': 'D009599'}, {'text': 'hypotension', 'type': 'Disease', 'start': 949, 'end': 960, 'mesh': 'D007022'}, {'text': 'AVP', 'type': 'Chemical', 'start': 1030, 'end': 1033, 'mesh': 'D001127'}, {'text': 'AVP', 'type': 'Chemical', 'start': 1139, 'end': 1142, 'mesh': 'D001127'}, {'text': 'AVP', 'type': 'Chemical', 'start': 1280, 'end': 1283, 'mesh': 'D001127'}, {'text': 'AVP', 'type': 'Chemical', 'start': 1379, 'end': 1382, 'mesh': 'D001127'}, {'text': 'SN', 'type': 'Chemical', 'start': 1390, 'end': 1392, 'mesh': 'D009599'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1401, 'end': 1412, 'mesh': 'D007022'}, {'text': 'AVP', 'type': 'Chemical', 'start': 1459, 'end': 1462, 'mesh': 'D001127'}, {'text': 'AVP', 'type': 'Chemical', 'start': 1473, 'end': 1476, 'mesh': 'D001127'}, {'text': 'Phe', 'type': 'Chemical', 'start': 1498, 'end': 1501, 'mesh': 'D010656'}, {'text': 'AVP', 'type': 'Chemical', 'start': 1569, 'end': 1572, 'mesh': 'D001127'}]"
+1280,8308951,Cutaneous exposure to warfarin-like anticoagulant causing an intracerebral hemorrhage: a case report.,"A case of intercerebral hematoma due to warfarin-induced coagulopathy is presented. The 39-year-old woman had spread a warfarin-type rat poison around her house weekly using her bare hands, with no washing post application. Percutaneous absorption of warfarin causing coagulopathy, reported three times in the past, is a significant risk if protective measures, such as gloves, are not used. An adverse drug interaction with piroxicam, which she took occasionally, may have exacerbated the coagulopathy.","[{'text': 'warfarin', 'type': 'Chemical', 'start': 22, 'end': 30, 'mesh': 'D014859'}, {'text': 'intracerebral hemorrhage', 'type': 'Disease', 'start': 61, 'end': 85, 'mesh': 'D002543'}, {'text': 'hematoma', 'type': 'Disease', 'start': 126, 'end': 134, 'mesh': 'D006406'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 142, 'end': 150, 'mesh': 'D014859'}, {'text': 'coagulopathy', 'type': 'Disease', 'start': 159, 'end': 171, 'mesh': 'D001778'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 221, 'end': 229, 'mesh': 'D014859'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 353, 'end': 361, 'mesh': 'D014859'}, {'text': 'coagulopathy', 'type': 'Disease', 'start': 370, 'end': 382, 'mesh': 'D001778'}, {'text': 'piroxicam', 'type': 'Chemical', 'start': 527, 'end': 536, 'mesh': 'D010894'}, {'text': 'coagulopathy', 'type': 'Disease', 'start': 592, 'end': 604, 'mesh': 'D001778'}]"
+1281,8312343,Pediatric heart transplantation without chronic maintenance steroids.,"From 1986 to February 1993, 40 children aged 2 months to 18 years (average age 10.4 +/- 5.8 years) underwent heart transplantation. Indications for transplantation were idiopathic cardiomyopathy (52%), congenital heart disease (35%) with and without prior repair (71% and 29%, respectively), hypertrophic cardiomyopathy (5%), valvular heart disease (3%), and doxorubicin cardiomyopathy (5%). Patients were managed with cyclosporine and azathioprine. No prophylaxis with antilymphocyte globulin was used. Steroids were given to 39% of patients for refractory rejection, but weaning was always attempted and generally successful (64%). Five patients (14%) received maintenance steroids. Four patients died in the perioperative period and one died 4 months later. There have been no deaths related to rejection or infection. Average follow-up was 36 +/- 19 months (range 1 to 65 months). Cumulative survival is 88% at 5 years. In patients less than 7 years of age, rejection was monitored noninvasively. In the first postoperative month, 89% of patients were treated for rejection. Freedom from serious infections was 83% at 1 month and 65% at 1 year. Cytomegalovirus infections were treated successfully with ganciclovir in 11 patients. No impairment of growth was observed in children who underwent transplantation compared with a control population. Twenty-one patients (60%) have undergone annual catheterizations and no sign of graft atherosclerosis has been observed. Seizures occurred in five patients (14%) and hypertension was treated in 10 patients (28%). No patient was disabled and no lymphoproliferative disorder was observed.(ABSTRACT TRUNCATED AT 250 WORDS)","[{'text': 'steroids', 'type': 'Chemical', 'start': 60, 'end': 68, 'mesh': 'D013256'}, {'text': 'idiopathic cardiomyopathy', 'type': 'Disease', 'start': 239, 'end': 264, 'mesh': 'D002311'}, {'text': 'congenital heart disease', 'type': 'Disease', 'start': 272, 'end': 296, 'mesh': 'D006331'}, {'text': 'hypertrophic cardiomyopathy', 'type': 'Disease', 'start': 362, 'end': 389, 'mesh': 'D002312'}, {'text': 'valvular heart disease', 'type': 'Disease', 'start': 396, 'end': 418, 'mesh': 'D006349'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 429, 'end': 440, 'mesh': 'D004317'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 441, 'end': 455, 'mesh': 'D009202'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 489, 'end': 501, 'mesh': 'D016572'}, {'text': 'azathioprine', 'type': 'Chemical', 'start': 506, 'end': 518, 'mesh': 'D001379'}, {'text': 'Steroids', 'type': 'Chemical', 'start': 574, 'end': 582, 'mesh': 'D013256'}, {'text': 'steroids', 'type': 'Chemical', 'start': 745, 'end': 753, 'mesh': 'D013256'}, {'text': 'infection', 'type': 'Disease', 'start': 881, 'end': 890, 'mesh': 'D007239'}, {'text': 'infections', 'type': 'Disease', 'start': 1170, 'end': 1180, 'mesh': 'D007239'}, {'text': 'Cytomegalovirus infections', 'type': 'Disease', 'start': 1219, 'end': 1245, 'mesh': 'D003586'}, {'text': 'ganciclovir', 'type': 'Chemical', 'start': 1277, 'end': 1288, 'mesh': 'D015774'}, {'text': 'atherosclerosis', 'type': 'Disease', 'start': 1506, 'end': 1521, 'mesh': 'D050197'}, {'text': 'Seizures', 'type': 'Disease', 'start': 1541, 'end': 1549, 'mesh': 'D012640'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1586, 'end': 1598, 'mesh': 'D006973'}, {'text': 'lymphoproliferative disorder', 'type': 'Disease', 'start': 1664, 'end': 1692, 'mesh': 'D008232'}]"
+1282,8312983,Delirium during fluoxetine treatment. A case report.,"The correlation between high serum tricyclic antidepressant concentrations and central nervous system side effects has been well established. Only a few reports exist, however, on the relationship between the serum concentrations of selective serotonin reuptake inhibitors (SSRIs) and their toxic effects. In some cases, a high serum concentration of citalopram (> 600 nmol/L) in elderly patients has been associated with increased somnolence and movement difficulties. Widespread cognitive disorders, such as delirium, have not been previously linked with high blood levels of SSRIs. In this report, we describe a patient with acute hyperkinetic delirium connected with a high serum total fluoxetine (fluoxetine plus desmethylfluoxetine) concentration.","[{'text': 'Delirium', 'type': 'Disease', 'start': 0, 'end': 8, 'mesh': 'D003693'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 16, 'end': 26, 'mesh': 'D005473'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 296, 'end': 305, 'mesh': 'D012701'}, {'text': 'citalopram', 'type': 'Chemical', 'start': 404, 'end': 414, 'mesh': 'D015283'}, {'text': 'somnolence', 'type': 'Disease', 'start': 485, 'end': 495, 'mesh': 'D006970'}, {'text': 'movement difficulties', 'type': 'Disease', 'start': 500, 'end': 521, 'mesh': 'D020820'}, {'text': 'cognitive disorders', 'type': 'Disease', 'start': 534, 'end': 553, 'mesh': 'D003072'}, {'text': 'delirium', 'type': 'Disease', 'start': 563, 'end': 571, 'mesh': 'D003693'}, {'text': 'hyperkinetic', 'type': 'Disease', 'start': 687, 'end': 699, 'mesh': 'D006948'}, {'text': 'delirium', 'type': 'Disease', 'start': 700, 'end': 708, 'mesh': 'D003693'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 743, 'end': 753, 'mesh': 'D005473'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 755, 'end': 765, 'mesh': 'D005473'}, {'text': 'desmethylfluoxetine', 'type': 'Chemical', 'start': 771, 'end': 790, 'mesh': 'C036139'}]"
+1283,8318674,Pulmonary edema and shock after high-dose aracytine-C for lymphoma; possible role of TNF-alpha and PAF.,"Four out of 23 consecutive patients treated with high-dose Ara-C for lymphomas in our institution developed a strikingly similar syndrome during the perfusion. It was characterized by the onset of fever, diarrhea, shock, pulmonary edema, acute renal failure, metabolic acidosis, weight gain and leukocytosis. Thorough bacteriological screening failed to provide evidence of infection. Sequential biological assays of IL-1, IL-2, TNF and PAF were performed during Ara-C infusion to ten patients, including the four who developed the syndrome. TNF and PAF activity was found in the serum of respectively two and four of the cases, but not in the six controls. As TNF and PAF are thought to be involved in the development of septic shock and adult respiratory distress syndrome, we hypothesize that high-dose Ara-C may be associated with cytokine release.","[{'text': 'Pulmonary edema', 'type': 'Disease', 'start': 0, 'end': 15, 'mesh': 'D011654'}, {'text': 'shock', 'type': 'Disease', 'start': 20, 'end': 25, 'mesh': 'D012769'}, {'text': 'aracytine-C', 'type': 'Chemical', 'start': 42, 'end': 53, 'mesh': 'D003561'}, {'text': 'lymphoma', 'type': 'Disease', 'start': 58, 'end': 66, 'mesh': 'D008223'}, {'text': 'Ara-C', 'type': 'Chemical', 'start': 163, 'end': 168, 'mesh': 'D003561'}, {'text': 'lymphomas', 'type': 'Disease', 'start': 173, 'end': 182, 'mesh': 'D008223'}, {'text': 'fever', 'type': 'Disease', 'start': 301, 'end': 306, 'mesh': 'D005334'}, {'text': 'diarrhea', 'type': 'Disease', 'start': 308, 'end': 316, 'mesh': 'D003967'}, {'text': 'shock', 'type': 'Disease', 'start': 318, 'end': 323, 'mesh': 'D012769'}, {'text': 'pulmonary edema', 'type': 'Disease', 'start': 325, 'end': 340, 'mesh': 'D011654'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 342, 'end': 361, 'mesh': 'D058186'}, {'text': 'metabolic acidosis', 'type': 'Disease', 'start': 363, 'end': 381, 'mesh': 'D000138'}, {'text': 'weight gain', 'type': 'Disease', 'start': 383, 'end': 394, 'mesh': 'D015430'}, {'text': 'leukocytosis', 'type': 'Disease', 'start': 399, 'end': 411, 'mesh': 'D007964'}, {'text': 'infection', 'type': 'Disease', 'start': 478, 'end': 487, 'mesh': 'D007239'}, {'text': 'Ara-C', 'type': 'Chemical', 'start': 567, 'end': 572, 'mesh': 'D003561'}, {'text': 'shock', 'type': 'Disease', 'start': 833, 'end': 838, 'mesh': 'D012769'}, {'text': 'adult respiratory distress syndrome', 'type': 'Disease', 'start': 843, 'end': 878, 'mesh': 'D012128'}, {'text': 'Ara-C', 'type': 'Chemical', 'start': 910, 'end': 915, 'mesh': 'D003561'}]"
+1284,8392553,Protective effect of clentiazem against epinephrine-induced cardiac injury in rats.,"We investigated the effects of clentiazem, a 1,5-benzothiazepine calcium antagonist, on epinephrine-induced cardiomyopathy in rats. With 2-week chronic epinephrine infusion, 16 of 30 rats died within 4 days, and severe ischemic lesions and fibrosis of the left ventricles were observed. In epinephrine-treated rats, left atrial and left ventricular papillary muscle contractile responses to isoproterenol were reduced, but responses to calcium were normal or enhanced compared to controls. Left ventricular alpha and beta adrenoceptor densities were also reduced compared to controls. Treatment with clentiazem prevented epinephrine-induced death (P < .05), and attenuated the ventricular ischemic lesions and fibrosis, in a dose-dependent manner. Left atrial and left ventricular papillary muscle contractile responses to isoproterenol were reduced compared to controls in groups treated with clentiazem alone, but combined with epinephrine, clentiazem restored left atrial responses and enhanced left ventricular papillary responses to isoproterenol. On the other hand clentiazem did not prevent epinephrine-induced down-regulation of alpha and beta adrenoceptors. Interestingly, clentiazem, infused alone, resulted in decreased adrenergic receptor densities in the left ventricle. Clentiazem also did not prevent the enhanced responses to calcium seen in the epinephrine-treated animals, although the high dose of clentiazem partially attenuated the maximal response to calcium compared to epinephrine-treated animals. In conclusion, clentiazem attenuated epinephrine-induced cardiac injury, possibly through its effect on the adrenergic pathway.","[{'text': 'clentiazem', 'type': 'Chemical', 'start': 21, 'end': 31, 'mesh': 'C056595'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 40, 'end': 51, 'mesh': 'D004837'}, {'text': 'cardiac injury', 'type': 'Disease', 'start': 60, 'end': 74, 'mesh': 'D006331'}, {'text': 'clentiazem', 'type': 'Chemical', 'start': 115, 'end': 125, 'mesh': 'C056595'}, {'text': '1,5-benzothiazepine', 'type': 'Chemical', 'start': 129, 'end': 148, 'mesh': 'C106746'}, {'text': 'calcium', 'type': 'Chemical', 'start': 149, 'end': 156, 'mesh': 'D002118'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 172, 'end': 183, 'mesh': 'D004837'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 192, 'end': 206, 'mesh': 'D009202'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 236, 'end': 247, 'mesh': 'D004837'}, {'text': 'ischemic lesions', 'type': 'Disease', 'start': 303, 'end': 319, 'mesh': 'D007511'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 324, 'end': 332, 'mesh': 'D005355'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 374, 'end': 385, 'mesh': 'D004837'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 475, 'end': 488, 'mesh': 'D007545'}, {'text': 'calcium', 'type': 'Chemical', 'start': 520, 'end': 527, 'mesh': 'D002118'}, {'text': 'clentiazem', 'type': 'Chemical', 'start': 684, 'end': 694, 'mesh': 'C056595'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 705, 'end': 716, 'mesh': 'D004837'}, {'text': 'ischemic lesions', 'type': 'Disease', 'start': 773, 'end': 789, 'mesh': 'D007511'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 794, 'end': 802, 'mesh': 'D005355'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 907, 'end': 920, 'mesh': 'D007545'}, {'text': 'clentiazem', 'type': 'Chemical', 'start': 978, 'end': 988, 'mesh': 'C056595'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 1014, 'end': 1025, 'mesh': 'D004837'}, {'text': 'clentiazem', 'type': 'Chemical', 'start': 1027, 'end': 1037, 'mesh': 'C056595'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1122, 'end': 1135, 'mesh': 'D007545'}, {'text': 'clentiazem', 'type': 'Chemical', 'start': 1155, 'end': 1165, 'mesh': 'C056595'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 1182, 'end': 1193, 'mesh': 'D004837'}, {'text': 'clentiazem', 'type': 'Chemical', 'start': 1266, 'end': 1276, 'mesh': 'C056595'}, {'text': 'Clentiazem', 'type': 'Chemical', 'start': 1368, 'end': 1378, 'mesh': 'C056595'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1426, 'end': 1433, 'mesh': 'D002118'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 1446, 'end': 1457, 'mesh': 'D004837'}, {'text': 'clentiazem', 'type': 'Chemical', 'start': 1501, 'end': 1511, 'mesh': 'C056595'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1557, 'end': 1564, 'mesh': 'D002118'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 1577, 'end': 1588, 'mesh': 'D004837'}, {'text': 'clentiazem', 'type': 'Chemical', 'start': 1621, 'end': 1631, 'mesh': 'C056595'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 1643, 'end': 1654, 'mesh': 'D004837'}, {'text': 'cardiac injury', 'type': 'Disease', 'start': 1663, 'end': 1677, 'mesh': 'D006331'}]"
+1285,8511251,Cocaine induced myocardial ischemia.,We report a case of myocardial ischemia induced by cocaine. The ischemia probably induced by coronary artery spasm was reversed by nitroglycerin and calcium blocking agents.,"[{'text': 'Cocaine', 'type': 'Chemical', 'start': 0, 'end': 7, 'mesh': 'D003042'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 16, 'end': 35, 'mesh': 'D017202'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 57, 'end': 76, 'mesh': 'D017202'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 88, 'end': 95, 'mesh': 'D003042'}, {'text': 'ischemia', 'type': 'Disease', 'start': 101, 'end': 109, 'mesh': 'D007511'}, {'text': 'coronary artery spasm', 'type': 'Disease', 'start': 130, 'end': 151, 'mesh': 'D003329'}, {'text': 'nitroglycerin', 'type': 'Chemical', 'start': 168, 'end': 181, 'mesh': 'D005996'}, {'text': 'calcium', 'type': 'Chemical', 'start': 186, 'end': 193, 'mesh': 'D002118'}]"
+1286,8603459,Doxorubicin-induced cardiotoxicity monitored by ECG in freely moving mice. A new model to test potential protectors.,"In laboratory animals, histology is most commonly used to study doxorubicin-induced cardiotoxicity. However, for monitoring during treatment, large numbers of animals are needed. Recently we developed a new method to measure ECG values in freely moving mice by telemetry. With this model we investigated the effect of chronic doxorubicin administration on the ECG of freely moving BALB/c mice and the efficacy of ICRF-187 as a protective agent. The ST interval significantly widened from 15.0 +/- 1.5 to 56.8 +/- 11.8 ms in week 10 (7 weekly doses of 4 mg/kg doxorubicin given i.v. plus 3 weeks of observation). The ECG of the control animals did not change during the entire study. After sacrifice the hearts of doxorubicin-treated animals were enlarged and the atria were hypertrophic. As this schedule exerted more toxicity than needed to investigate protective agents, the protection of ICRF-187 was determined using a dose schedule with lower general toxicity (6 weekly doses of 4 mg/kg doxorubicin given i.v. plus 2 weeks of observation). On this schedule, the animals' hearts appeared normal after sacrifice and ICRF-187 (50 mg/kg given i.p. 1 h before doxorubicin) provided almost full protection. These data were confirmed by histology. The results indicate that this new model is very sensitive and enables monitoring of the development of cardiotoxicity with time. These findings result in a model that allows the testing of protectors against doxorubicin-induced cardiotoxicity as demonstrated by the protection provided by ICRF-187.","[{'text': 'Doxorubicin', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 20, 'end': 34, 'mesh': 'D066126'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 181, 'end': 192, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 201, 'end': 215, 'mesh': 'D066126'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 443, 'end': 454, 'mesh': 'D004317'}, {'text': 'ICRF-187', 'type': 'Chemical', 'start': 530, 'end': 538, 'mesh': 'D064730'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 676, 'end': 687, 'mesh': 'D004317'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 830, 'end': 841, 'mesh': 'D004317'}, {'text': 'hypertrophic', 'type': 'Disease', 'start': 891, 'end': 903, 'mesh': 'D006984'}, {'text': 'toxicity', 'type': 'Disease', 'start': 935, 'end': 943, 'mesh': 'D064420'}, {'text': 'ICRF-187', 'type': 'Chemical', 'start': 1008, 'end': 1016, 'mesh': 'D064730'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1073, 'end': 1081, 'mesh': 'D064420'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1109, 'end': 1120, 'mesh': 'D004317'}, {'text': 'ICRF-187', 'type': 'Chemical', 'start': 1236, 'end': 1244, 'mesh': 'D064730'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1277, 'end': 1288, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1467, 'end': 1481, 'mesh': 'D066126'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1572, 'end': 1583, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1592, 'end': 1606, 'mesh': 'D066126'}, {'text': 'ICRF-187', 'type': 'Chemical', 'start': 1653, 'end': 1661, 'mesh': 'D064730'}]"
+1287,8659767,Epinephrine dysrhythmogenicity is not enhanced by subtoxic bupivacaine in dogs.,"Since bupivacaine and epinephrine may both precipitate dysrhythmias, circulating bupivacaine during regional anesthesia could potentiate dysrhythmogenic effects of epinephrine. We therefore examined whether bupivacaine alters the dysrhythmogenicity of subsequent administration of epinephrine in conscious, healthy dogs and in anesthetized dogs with myocardial infarction. Forty-one conscious dogs received 10 micrograms.kg-1.min-1 epinephrine. Seventeen animals responded with ventricular tachycardia (VT) within 3 min. After 3 h, these responders randomly received 1 or 2 mg/kg bupivacaine or saline over 5 min, followed by 10 micrograms.kg-1.min-1 epinephrine. In the bupivacaine groups, epinephrine caused fewer prodysrhythmic effects than without bupivacaine. VT appeared in fewer dogs and at a later time, and there were more sinoatrial beats and less ectopies. Epinephrine shortened QT less after bupivacaine than in control animals. One day after experimental myocardial infarction, six additional halothane-anesthetized dogs received 4 micrograms.kg-1.min-1 epinephrine until VT appeared. After 45 min, 1 mg/kg bupivacaine was injected over 5 min, again followed by 4 micrograms.kg-1.min-1 epinephrine. In these dogs, the prodysrhythmic response to epinephrine was also mitigated by preceding bupivacaine. Bupivacaine antagonizes epinephrine dysrhythmogenicity in conscious dogs susceptible to VT and in anesthetized dogs with spontaneous postinfarct dysrhythmias. There is no evidence that systemic subtoxic bupivacaine administration enhances the dysrhythmogenicity of subsequent epinephrine.","[{'text': 'Epinephrine', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D004837'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 59, 'end': 70, 'mesh': 'D002045'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 86, 'end': 97, 'mesh': 'D002045'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 102, 'end': 113, 'mesh': 'D004837'}, {'text': 'dysrhythmias', 'type': 'Disease', 'start': 135, 'end': 147, 'mesh': 'D001145'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 161, 'end': 172, 'mesh': 'D002045'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 244, 'end': 255, 'mesh': 'D004837'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 287, 'end': 298, 'mesh': 'D002045'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 361, 'end': 372, 'mesh': 'D004837'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 430, 'end': 451, 'mesh': 'D009203'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 512, 'end': 523, 'mesh': 'D004837'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 558, 'end': 581, 'mesh': 'D017180'}, {'text': 'VT', 'type': 'Disease', 'start': 583, 'end': 585, 'mesh': 'D017180'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 660, 'end': 671, 'mesh': 'D002045'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 731, 'end': 742, 'mesh': 'D004837'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 751, 'end': 762, 'mesh': 'D002045'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 771, 'end': 782, 'mesh': 'D004837'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 832, 'end': 843, 'mesh': 'D002045'}, {'text': 'VT', 'type': 'Disease', 'start': 845, 'end': 847, 'mesh': 'D017180'}, {'text': 'Epinephrine', 'type': 'Chemical', 'start': 948, 'end': 959, 'mesh': 'D004837'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 984, 'end': 995, 'mesh': 'D002045'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 1048, 'end': 1069, 'mesh': 'D009203'}, {'text': 'halothane', 'type': 'Chemical', 'start': 1086, 'end': 1095, 'mesh': 'D006221'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 1147, 'end': 1158, 'mesh': 'D004837'}, {'text': 'VT', 'type': 'Disease', 'start': 1165, 'end': 1167, 'mesh': 'D017180'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 1200, 'end': 1211, 'mesh': 'D002045'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 1279, 'end': 1290, 'mesh': 'D004837'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 1338, 'end': 1349, 'mesh': 'D004837'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 1382, 'end': 1393, 'mesh': 'D002045'}, {'text': 'Bupivacaine', 'type': 'Chemical', 'start': 1395, 'end': 1406, 'mesh': 'D002045'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 1419, 'end': 1430, 'mesh': 'D004837'}, {'text': 'VT', 'type': 'Disease', 'start': 1483, 'end': 1485, 'mesh': 'D017180'}, {'text': 'dysrhythmias', 'type': 'Disease', 'start': 1540, 'end': 1552, 'mesh': 'D001145'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 1598, 'end': 1609, 'mesh': 'D002045'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 1671, 'end': 1682, 'mesh': 'D004837'}]"
+1288,8667442,"Milk-alkali syndrome induced by 1,25(OH)2D in a patient with hypoparathyroidism.","Milk-alkali syndrome was first described 70 years ago in the context of the treatment of peptic ulcer disease with large amounts of calcium and alkali. Although with current ulcer therapy (H-2 blockers, omeprazole, and sucralfate), the frequency of milk-alkali syndrome has decreased significantly, the classic triad of hypercalcemia, alkalosis, and renal impairment remains the hallmark of the syndrome. Milk-alkali syndrome can present serious and occasionally life-threatening illness unless diagnosed and treated appropriately. This article presents a patient with hypoparathyroidism who was treated with calcium carbonate and calcitriol resulting in two admissions to the hospital for milk-alkali syndrome. The patient was successfully treated with intravenous pamidronate on his first admission and with hydrocortisone on the second. This illustrates intravenous pamidronate as a valuable therapeutic tool when milk-alkali syndrome presents as hypercalcemic emergency.","[{'text': 'Milk-alkali syndrome', 'type': 'Disease', 'start': 0, 'end': 20, 'mesh': 'D006934'}, {'text': '1,25(OH)2D', 'type': 'Chemical', 'start': 32, 'end': 42, 'mesh': 'D002117'}, {'text': 'hypoparathyroidism', 'type': 'Disease', 'start': 61, 'end': 79, 'mesh': 'D007011'}, {'text': 'Milk-alkali syndrome', 'type': 'Disease', 'start': 81, 'end': 101, 'mesh': 'D006934'}, {'text': 'peptic ulcer disease', 'type': 'Disease', 'start': 170, 'end': 190, 'mesh': 'D010437'}, {'text': 'calcium', 'type': 'Chemical', 'start': 213, 'end': 220, 'mesh': 'D002118'}, {'text': 'alkali', 'type': 'Chemical', 'start': 225, 'end': 231, 'mesh': 'D000468'}, {'text': 'ulcer', 'type': 'Disease', 'start': 255, 'end': 260, 'mesh': 'D014456'}, {'text': 'omeprazole', 'type': 'Chemical', 'start': 284, 'end': 294, 'mesh': 'D009853'}, {'text': 'sucralfate', 'type': 'Chemical', 'start': 300, 'end': 310, 'mesh': 'D013392'}, {'text': 'milk-alkali syndrome', 'type': 'Disease', 'start': 330, 'end': 350, 'mesh': 'D006934'}, {'text': 'hypercalcemia', 'type': 'Disease', 'start': 401, 'end': 414, 'mesh': 'D006934'}, {'text': 'alkalosis', 'type': 'Disease', 'start': 416, 'end': 425, 'mesh': 'D000471'}, {'text': 'renal impairment', 'type': 'Disease', 'start': 431, 'end': 447, 'mesh': 'D051437'}, {'text': 'Milk-alkali syndrome', 'type': 'Disease', 'start': 486, 'end': 506, 'mesh': 'D006934'}, {'text': 'hypoparathyroidism', 'type': 'Disease', 'start': 650, 'end': 668, 'mesh': 'D007011'}, {'text': 'calcium carbonate', 'type': 'Chemical', 'start': 690, 'end': 707, 'mesh': 'D002119'}, {'text': 'calcitriol', 'type': 'Chemical', 'start': 712, 'end': 722, 'mesh': 'D002117'}, {'text': 'milk-alkali syndrome', 'type': 'Disease', 'start': 771, 'end': 791, 'mesh': 'D006934'}, {'text': 'pamidronate', 'type': 'Chemical', 'start': 847, 'end': 858, 'mesh': 'C019248'}, {'text': 'hydrocortisone', 'type': 'Chemical', 'start': 891, 'end': 905, 'mesh': 'D006854'}, {'text': 'pamidronate', 'type': 'Chemical', 'start': 950, 'end': 961, 'mesh': 'C019248'}, {'text': 'milk-alkali syndrome', 'type': 'Disease', 'start': 998, 'end': 1018, 'mesh': 'D006934'}, {'text': 'hypercalcemic emergency', 'type': 'Disease', 'start': 1031, 'end': 1054, 'mesh': 'D006934'}]"
+1289,8748050,Encephalopathy during amitriptyline therapy: are neuroleptic malignant syndrome and serotonin syndrome spectrum disorders?,"This report describes a case of encephalopathy developed in the course of amitriptyline therapy, during a remission of unipolar depression. This patient could have been diagnosed as having either neuroleptic malignant syndrome (NMS) or serotonin syndrome (SS). The major determinant of the symptoms may have been dopamine/serotonin imbalance in the central nervous system. The NMS-like encephalopathy that develops in association with the use of antidepressants indicates that NMS and SS are spectrum disorders induced by drugs with both antidopaminergic and serotonergic effects.","[{'text': 'Encephalopathy', 'type': 'Disease', 'start': 0, 'end': 14, 'mesh': 'D001927'}, {'text': 'amitriptyline', 'type': 'Chemical', 'start': 22, 'end': 35, 'mesh': 'D000639'}, {'text': 'neuroleptic malignant syndrome', 'type': 'Disease', 'start': 49, 'end': 79, 'mesh': 'D009459'}, {'text': 'serotonin syndrome', 'type': 'Disease', 'start': 84, 'end': 102, 'mesh': 'D020230'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 155, 'end': 169, 'mesh': 'D001927'}, {'text': 'amitriptyline', 'type': 'Chemical', 'start': 197, 'end': 210, 'mesh': 'D000639'}, {'text': 'unipolar depression', 'type': 'Disease', 'start': 242, 'end': 261, 'mesh': 'D003866'}, {'text': 'neuroleptic malignant syndrome', 'type': 'Disease', 'start': 319, 'end': 349, 'mesh': 'D009459'}, {'text': 'NMS', 'type': 'Disease', 'start': 351, 'end': 354, 'mesh': 'D009459'}, {'text': 'serotonin syndrome', 'type': 'Disease', 'start': 359, 'end': 377, 'mesh': 'D020230'}, {'text': 'SS', 'type': 'Disease', 'start': 379, 'end': 381, 'mesh': 'D020230'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 436, 'end': 444, 'mesh': 'D004298'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 445, 'end': 454, 'mesh': 'D012701'}, {'text': 'NMS', 'type': 'Disease', 'start': 500, 'end': 503, 'mesh': 'D009459'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 509, 'end': 523, 'mesh': 'D001927'}, {'text': 'NMS', 'type': 'Disease', 'start': 600, 'end': 603, 'mesh': 'D009459'}, {'text': 'SS', 'type': 'Disease', 'start': 608, 'end': 610, 'mesh': 'D020230'}]"
+1290,8755612,Genetic separation of tumor growth and hemorrhagic phenotypes in an estrogen-induced tumor.,"Chronic administration of estrogen to the Fischer 344 (F344) rat induces growth of large, hemorrhagic pituitary tumors. Ten weeks of diethylstilbestrol (DES) treatment caused female F344 rat pituitaries to grow to an average of 109.2 +/- 6.3 mg (mean +/- SE) versus 11.3 +/- 1.4 mg for untreated rats, and to become highly hemorrhagic. The same DES treatment produced no significant growth (8.9 +/- 0.5 mg for treated females versus 8.7 +/- 1.1 for untreated females) or morphological changes in Brown Norway (BN) rat pituitaries. An F1 hybrid of F344 and BN exhibited significant pituitary growth after 10 weeks of DES treatment with an average mass of 26.3 +/- 0.7 mg compared with 8.6 +/- 0.9 mg for untreated rats. Surprisingly, the F1 hybrid tumors were not hemorrhagic and had hemoglobin content and outward appearance identical to that of BN. Expression of both growth and morphological changes is due to multiple genes. However, while DES-induced pituitary growth exhibited quantitative, additive inheritance, the hemorrhagic phenotype exhibited recessive, epistatic inheritance. Only 5 of the 160 F2 pituitaries exhibited the hemorrhagic phenotype; 36 of the 160 F2 pituitaries were in the F344 range of mass, but 31 of these were not hemorrhagic, indicating that the hemorrhagic phenotype is not merely a consequence of extensive growth. The hemorrhagic F2 pituitaries were all among the most massive, indicating that some of the genes regulate both phenotypes.","[{'text': 'tumor', 'type': 'Disease', 'start': 22, 'end': 27, 'mesh': 'D009369'}, {'text': 'hemorrhagic', 'type': 'Disease', 'start': 39, 'end': 50, 'mesh': 'D006470'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 68, 'end': 76, 'mesh': 'D004967'}, {'text': 'tumor', 'type': 'Disease', 'start': 85, 'end': 90, 'mesh': 'D009369'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 118, 'end': 126, 'mesh': 'D004967'}, {'text': 'hemorrhagic', 'type': 'Disease', 'start': 182, 'end': 193, 'mesh': 'D006470'}, {'text': 'pituitary tumors', 'type': 'Disease', 'start': 194, 'end': 210, 'mesh': 'D010911'}, {'text': 'diethylstilbestrol', 'type': 'Chemical', 'start': 225, 'end': 243, 'mesh': 'D004054'}, {'text': 'DES', 'type': 'Chemical', 'start': 245, 'end': 248, 'mesh': 'D004054'}, {'text': 'hemorrhagic', 'type': 'Disease', 'start': 415, 'end': 426, 'mesh': 'D006470'}, {'text': 'DES', 'type': 'Chemical', 'start': 437, 'end': 440, 'mesh': 'D004054'}, {'text': 'DES', 'type': 'Chemical', 'start': 708, 'end': 711, 'mesh': 'D004054'}, {'text': 'tumors', 'type': 'Disease', 'start': 839, 'end': 845, 'mesh': 'D009369'}, {'text': 'hemorrhagic', 'type': 'Disease', 'start': 855, 'end': 866, 'mesh': 'D006470'}, {'text': 'DES', 'type': 'Chemical', 'start': 1035, 'end': 1038, 'mesh': 'D004054'}, {'text': 'hemorrhagic', 'type': 'Disease', 'start': 1114, 'end': 1125, 'mesh': 'D006470'}, {'text': 'hemorrhagic', 'type': 'Disease', 'start': 1227, 'end': 1238, 'mesh': 'D006470'}, {'text': 'hemorrhagic', 'type': 'Disease', 'start': 1336, 'end': 1347, 'mesh': 'D006470'}, {'text': 'hemorrhagic', 'type': 'Disease', 'start': 1369, 'end': 1380, 'mesh': 'D006470'}, {'text': 'hemorrhagic', 'type': 'Disease', 'start': 1444, 'end': 1455, 'mesh': 'D006470'}]"
+1291,8808730,Increased expression of neuronal nitric oxide synthase in bladder afferent pathways following chronic bladder irritation.,"Immunocytochemical techniques were used to examine alterations in the expression of neuronal nitric oxide synthase (NOS) in bladder pathways following acute and chronic irritation of the urinary tract of the rat. Chemical cystitis was induced by cyclophosphamide (CYP) which is metabolized to acrolein, an irritant eliminated in the urine. Injection of CYP (n = 10, 75 mg/kg, i.p.) 2 hours prior to perfusion (acute treatment) of the animals increased Fos-immunoreactivity (IR) in neurons in the dorsal commissure, dorsal horn, and autonomic regions of spinal segments (L1-L2 and L6-S1) which receive afferent inputs from the bladder, urethra, and ureter. Fos-IR in the spinal cord was not changed in rats receiving chronic CYP treatment (n = 15, 75 mg/kg, i.p., every 3rd day for 2 weeks). In control animals and in animals treated acutely with CYP, only small numbers of NOS-IR cells (0.5-0.7 cell profiles/sections) were detected in the L6-S1 dorsal root ganglia (DRG). Chronic CYP administration significantly (P < or = .002) increased bladder weight by 60% and increased (7- to 11-fold) the numbers of NOS-immunoreactive (IR) afferent neurons in the L6-S1 DRG. A small increase (1.5-fold) also occurred in the L1 DRG, but no change was detected in the L2 and L5 DRG. Bladder afferent cells in the L6-S1 DRG labeled by Fluorogold (40 microliters) injected into the bladder wall did not exhibit NOS-IR in control animals; however, following chronic CYP administration, a significant percentage of bladder afferent neurons were NOS-IR: L6 (19.8 +/- 4.6%) and S1 (25.3 +/- 2.9%). These results indicate that neuronal gene expression in visceral sensory pathways can be upregulated by chemical irritation of afferent receptors in the urinary tract and/or that pathological changes in the urinary tract can initiate chemical signals that alter the chemical properties of visceral afferent neurons.","[{'text': 'nitric oxide', 'type': 'Chemical', 'start': 33, 'end': 45, 'mesh': 'D009569'}, {'text': 'bladder irritation', 'type': 'Disease', 'start': 102, 'end': 120, 'mesh': 'D001745'}, {'text': 'nitric oxide', 'type': 'Chemical', 'start': 215, 'end': 227, 'mesh': 'D009569'}, {'text': 'irritation of the urinary tract', 'type': 'Disease', 'start': 291, 'end': 322, 'mesh': 'D014570'}, {'text': 'cystitis', 'type': 'Disease', 'start': 344, 'end': 352, 'mesh': 'D003556'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 368, 'end': 384, 'mesh': 'D003520'}, {'text': 'CYP', 'type': 'Chemical', 'start': 386, 'end': 389, 'mesh': 'D003520'}, {'text': 'acrolein', 'type': 'Chemical', 'start': 415, 'end': 423, 'mesh': 'D000171'}, {'text': 'CYP', 'type': 'Chemical', 'start': 475, 'end': 478, 'mesh': 'D003520'}, {'text': 'CYP', 'type': 'Chemical', 'start': 846, 'end': 849, 'mesh': 'D003520'}, {'text': 'CYP', 'type': 'Chemical', 'start': 968, 'end': 971, 'mesh': 'D003520'}, {'text': 'CYP', 'type': 'Chemical', 'start': 1103, 'end': 1106, 'mesh': 'D003520'}, {'text': 'CYP', 'type': 'Chemical', 'start': 1574, 'end': 1577, 'mesh': 'D003520'}]"
+1292,8819482,"Effects of a new calcium antagonist, CD-832, on isoproterenol-induced myocardial ischemia in dogs with partial coronary stenosis.","Effects of CD-832 on isoproterenol (ISO)-induced myocardial ischemia were studied in dogs with partial coronary stenosis of the left circumflex coronary artery and findings were compared with those for nifedipine or diltiazem. In the presence of coronary artery stenosis, 3-min periods of intracoronary ISO infusion (10 ng/kg/min) increased heart rate and maximal rate of left ventricular pressure rise, which resulted in a decrease in percentage segmental shortening and ST-segment elevation of the epicardial electrocardiogram. After the control ISO infusion with stenosis was performed, equihypotensive doses of CD-832 (3 and 10 micrograms/kg/min, n = 7), nifedipine (1 and 3 micrograms/kg/min, n = 9) or diltiazem (10 and 30 micrograms/kg/min, n = 7) were infused 5 min before and during the second and third ISO infusion. Both CD-832 and diltiazem, but not nifedipine, significantly reduced the increase in heart rate induced by ISO infusion. In contrast to nifedipine, CD-832 (10 micrograms/kg/min) prevented the decrease in percentage segmental shortening from 32 +/- 12% to 115 +/- 26% of the control value (P < .01) and ST-segment elevation from 5.6 +/- 1.0 mV to 1.6 +/- 1.3 mV (P < .01) at 3 min after ISO infusion with stenosis. Diltiazem (30 micrograms/kg/min) also prevented the decrease in percentage segmental shortening from 34 +/- 14% to 63 +/- 18% of the control value (P < .05) and ST-segment elevation from 4.7 +/- 0.7 mV to 2.1 +/- 0.7 mV (P < .01) at 3 min after ISO infusion with stenosis. These data show that CD-832 improves myocardial ischemia during ISO infusion with stenosis and suggest that the negative chronotropic property of CD-832 plays a major role in the beneficial effects of CD-832.","[{'text': 'calcium', 'type': 'Chemical', 'start': 17, 'end': 24, 'mesh': 'D002118'}, {'text': 'CD-832', 'type': 'Chemical', 'start': 37, 'end': 43, 'mesh': 'C082828'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 48, 'end': 61, 'mesh': 'D007545'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 70, 'end': 89, 'mesh': 'D017202'}, {'text': 'coronary stenosis', 'type': 'Disease', 'start': 111, 'end': 128, 'mesh': 'D023921'}, {'text': 'CD-832', 'type': 'Chemical', 'start': 141, 'end': 147, 'mesh': 'C082828'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 151, 'end': 164, 'mesh': 'D007545'}, {'text': 'ISO', 'type': 'Chemical', 'start': 166, 'end': 169, 'mesh': 'D007545'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 179, 'end': 198, 'mesh': 'D017202'}, {'text': 'coronary stenosis', 'type': 'Disease', 'start': 233, 'end': 250, 'mesh': 'D023921'}, {'text': 'nifedipine', 'type': 'Chemical', 'start': 332, 'end': 342, 'mesh': 'D009543'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 346, 'end': 355, 'mesh': 'D004110'}, {'text': 'coronary artery stenosis', 'type': 'Disease', 'start': 376, 'end': 400, 'mesh': 'D023921'}, {'text': 'ISO', 'type': 'Chemical', 'start': 433, 'end': 436, 'mesh': 'D007545'}, {'text': 'ISO', 'type': 'Chemical', 'start': 678, 'end': 681, 'mesh': 'D007545'}, {'text': 'stenosis', 'type': 'Disease', 'start': 696, 'end': 704, 'mesh': 'D003251'}, {'text': 'CD-832', 'type': 'Chemical', 'start': 745, 'end': 751, 'mesh': 'C082828'}, {'text': 'nifedipine', 'type': 'Chemical', 'start': 789, 'end': 799, 'mesh': 'D009543'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 838, 'end': 847, 'mesh': 'D004110'}, {'text': 'ISO', 'type': 'Chemical', 'start': 943, 'end': 946, 'mesh': 'D007545'}, {'text': 'CD-832', 'type': 'Chemical', 'start': 962, 'end': 968, 'mesh': 'C082828'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 973, 'end': 982, 'mesh': 'D004110'}, {'text': 'nifedipine', 'type': 'Chemical', 'start': 992, 'end': 1002, 'mesh': 'D009543'}, {'text': 'ISO', 'type': 'Chemical', 'start': 1064, 'end': 1067, 'mesh': 'D007545'}, {'text': 'nifedipine', 'type': 'Chemical', 'start': 1093, 'end': 1103, 'mesh': 'D009543'}, {'text': 'CD-832', 'type': 'Chemical', 'start': 1105, 'end': 1111, 'mesh': 'C082828'}, {'text': 'ISO', 'type': 'Chemical', 'start': 1343, 'end': 1346, 'mesh': 'D007545'}, {'text': 'stenosis', 'type': 'Disease', 'start': 1361, 'end': 1369, 'mesh': 'D003251'}, {'text': 'Diltiazem', 'type': 'Chemical', 'start': 1371, 'end': 1380, 'mesh': 'D004110'}, {'text': 'ISO', 'type': 'Chemical', 'start': 1616, 'end': 1619, 'mesh': 'D007545'}, {'text': 'stenosis', 'type': 'Disease', 'start': 1634, 'end': 1642, 'mesh': 'D003251'}, {'text': 'CD-832', 'type': 'Chemical', 'start': 1665, 'end': 1671, 'mesh': 'C082828'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 1681, 'end': 1700, 'mesh': 'D017202'}, {'text': 'ISO', 'type': 'Chemical', 'start': 1708, 'end': 1711, 'mesh': 'D007545'}, {'text': 'stenosis', 'type': 'Disease', 'start': 1726, 'end': 1734, 'mesh': 'D003251'}, {'text': 'CD-832', 'type': 'Chemical', 'start': 1790, 'end': 1796, 'mesh': 'C082828'}, {'text': 'CD-832', 'type': 'Chemical', 'start': 1845, 'end': 1851, 'mesh': 'C082828'}]"
+1293,8825380,The effect of recombinant human insulin-like growth factor-I on chronic puromycin aminonucleoside nephropathy in rats.,"We recently demonstrated that recombinant hGH exacerbates renal functional and structural injury in chronic puromycin aminonucleoside (PAN) nephropathy, an experimental model of glomerular disease. Therefore, we examined whether recombinant human (rh) IGF-I is a safer alternative for the treatment of growth failure in rats with chronic PAN nephropathy. The glomerulopathy was induced by seven serial injections of PAN over 12 wk. Experimental animals (n = 6) received rhIGF-I, 400 micrograms/d, whereas control rats (n = 6) received the vehicle. rhIGF-I improved weight gain by 14% (p < 0.05), without altering hematocrit or blood pressure in rats with renal disease. Urinary protein excretion was unaltered by rhIGF-I treatment in rats with chronic PAN nephropathy. After 12 wk, the inulin clearance was higher in rhIGF-I-treated rats, 0.48 +/- 0.08 versus 0.24 +/- 0.06 mL/min/100 g of body weight in untreated PAN nephropathy animals, p < 0.05. The improvement in GFR was not associated with enhanced glomerular hypertrophy or increased segmental glomerulosclerosis, tubulointerstitial injury, or renal cortical malondialdehyde content. In rats with PAN nephropathy, administration of rhIGF-I increased IGF-I and GH receptor gene expression, without altering the steady state level of IGF-I receptor mRNA. In normal rats with intact kidneys, rhIGF-I administration (n = 4) did not alter weight gain, blood pressure, proteinuria, GFR, glomerular planar area, renal cortical malondialdehyde content, or glomerular or tubulointerstitial damage, compared with untreated animals (n = 4). rhIGF-I treatment reduced the steady state renal IGF-I mRNA level but did not modify gene expression of the IGF-I or GH receptors. We conclude that: 1) administration of rhIGF-I improves growth and GFR in rats with chronic PAN nephropathy and 2) unlike rhGH, long-term use of rhIGF-I does not worsen renal functional and structural injury in this disease model.","[{'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 72, 'end': 97, 'mesh': 'D011692'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 98, 'end': 109, 'mesh': 'D007674'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 227, 'end': 252, 'mesh': 'D011692'}, {'text': 'PAN', 'type': 'Chemical', 'start': 254, 'end': 257, 'mesh': 'D011692'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 259, 'end': 270, 'mesh': 'D007674'}, {'text': 'glomerular disease', 'type': 'Disease', 'start': 297, 'end': 315, 'mesh': 'D007674'}, {'text': 'growth failure', 'type': 'Disease', 'start': 421, 'end': 435, 'mesh': 'D006130'}, {'text': 'PAN', 'type': 'Chemical', 'start': 457, 'end': 460, 'mesh': 'D011692'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 461, 'end': 472, 'mesh': 'D007674'}, {'text': 'glomerulopathy', 'type': 'Disease', 'start': 478, 'end': 492, 'mesh': 'D007674'}, {'text': 'PAN', 'type': 'Chemical', 'start': 535, 'end': 538, 'mesh': 'D011692'}, {'text': 'renal disease', 'type': 'Disease', 'start': 774, 'end': 787, 'mesh': 'D007674'}, {'text': 'PAN', 'type': 'Chemical', 'start': 871, 'end': 874, 'mesh': 'D011692'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 875, 'end': 886, 'mesh': 'D007674'}, {'text': 'PAN', 'type': 'Chemical', 'start': 1034, 'end': 1037, 'mesh': 'D011692'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1038, 'end': 1049, 'mesh': 'D007674'}, {'text': 'glomerular hypertrophy', 'type': 'Disease', 'start': 1125, 'end': 1147, 'mesh': 'D007674'}, {'text': 'glomerulosclerosis', 'type': 'Disease', 'start': 1171, 'end': 1189, 'mesh': 'D005921'}, {'text': 'tubulointerstitial injury', 'type': 'Disease', 'start': 1191, 'end': 1216, 'mesh': '-1'}, {'text': 'malondialdehyde', 'type': 'Chemical', 'start': 1236, 'end': 1251, 'mesh': 'D008315'}, {'text': 'PAN', 'type': 'Chemical', 'start': 1274, 'end': 1277, 'mesh': 'D011692'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1278, 'end': 1289, 'mesh': 'D007674'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1540, 'end': 1551, 'mesh': 'D011507'}, {'text': 'malondialdehyde', 'type': 'Chemical', 'start': 1597, 'end': 1612, 'mesh': 'D008315'}, {'text': 'tubulointerstitial damage', 'type': 'Disease', 'start': 1639, 'end': 1664, 'mesh': 'D007674'}, {'text': 'PAN', 'type': 'Chemical', 'start': 1930, 'end': 1933, 'mesh': 'D011692'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1934, 'end': 1945, 'mesh': 'D007674'}]"
+1294,8829135,Nefiracetam (DM-9384) reverses apomorphine-induced amnesia of a passive avoidance response: delayed emergence of the memory retention effects.,"Nefiracetam is a novel pyrrolidone derivative which attenuates scopolamine-induced learning and post-training consolidation deficits. Given that apomorphine inhibits passive avoidance retention when given during training or in a defined 10-12h post-training period, we evaluated the ability of nefiracetam to attenuate amnesia induced by dopaminergic agonism. A step-down passive avoidance paradigm was employed and nefiracetam (3 mg/kg) and apomorphine (0.5 mg/kg) were given alone or in combination during training and at the 10-12h post-training period of consolidation. Co-administration of nefiracetam and apomorphine during training or 10h thereafter produced no significant anti-amnesic effect. However, administration of nefiracetam during training completely reversed the amnesia induced by apomorphine at the 10h post-training time and the converse was also true. These effects were not mediated by a dopaminergic mechanism as nefiracetam, at millimolar concentrations, failed to displace either [3H]SCH 23390 or [3H]spiperone binding from D1 or D2 dopamine receptor subtypes, respectively. It is suggested that nefiracetam augments molecular processes in the early stages of events which ultimately lead to consolidation of memory.","[{'text': 'Nefiracetam', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'C058876'}, {'text': 'DM-9384', 'type': 'Chemical', 'start': 13, 'end': 20, 'mesh': 'C058876'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 31, 'end': 42, 'mesh': 'D001058'}, {'text': 'amnesia', 'type': 'Disease', 'start': 51, 'end': 58, 'mesh': 'D000647'}, {'text': 'Nefiracetam', 'type': 'Chemical', 'start': 143, 'end': 154, 'mesh': 'C058876'}, {'text': 'pyrrolidone', 'type': 'Chemical', 'start': 166, 'end': 177, 'mesh': 'D011760'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 206, 'end': 217, 'mesh': 'D012601'}, {'text': 'learning and post-training consolidation deficits', 'type': 'Disease', 'start': 226, 'end': 275, 'mesh': 'D007859'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 288, 'end': 299, 'mesh': 'D001058'}, {'text': 'nefiracetam', 'type': 'Chemical', 'start': 437, 'end': 448, 'mesh': 'C058876'}, {'text': 'amnesia', 'type': 'Disease', 'start': 462, 'end': 469, 'mesh': 'D000647'}, {'text': 'nefiracetam', 'type': 'Chemical', 'start': 559, 'end': 570, 'mesh': 'C058876'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 585, 'end': 596, 'mesh': 'D001058'}, {'text': 'nefiracetam', 'type': 'Chemical', 'start': 738, 'end': 749, 'mesh': 'C058876'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 754, 'end': 765, 'mesh': 'D001058'}, {'text': 'nefiracetam', 'type': 'Chemical', 'start': 872, 'end': 883, 'mesh': 'C058876'}, {'text': 'amnesia', 'type': 'Disease', 'start': 924, 'end': 931, 'mesh': 'D000647'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 943, 'end': 954, 'mesh': 'D001058'}, {'text': 'nefiracetam', 'type': 'Chemical', 'start': 1080, 'end': 1091, 'mesh': 'C058876'}, {'text': 'SCH 23390', 'type': 'Chemical', 'start': 1153, 'end': 1162, 'mesh': 'C534628'}, {'text': 'spiperone', 'type': 'Chemical', 'start': 1170, 'end': 1179, 'mesh': 'D013134'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1202, 'end': 1210, 'mesh': 'D004298'}, {'text': 'nefiracetam', 'type': 'Chemical', 'start': 1265, 'end': 1276, 'mesh': 'C058876'}]"
+1295,8957205,Human corticotropin-releasing hormone and thyrotropin-releasing hormone modulate the hypercapnic ventilatory response in humans.,"Human corticotropin-releasing hormone (hCRH) and thyrotropin-releasing hormone (TRH) are known to stimulate ventilation after i.v. administration in humans. In a placebo-controlled, single-blind study we aimed to clarify if both peptides act by altering central chemosensitivity. Two subsequent CO2-rebreathing tests were performed in healthy young volunteers. During the first test 0.9% NaCl was given i.v.; during the second test 200 micrograms of hCRH (n = 12) or 400 micrograms of TRH (n = 6) was administered i.v. Nine subjects received 0.9% NaCl i.v. during both rebreathing manoeuvres. The CO2-response curves for the two tests were compared within the same subject. In the hCRH group a marked parallel shift of the CO2-response curve to the left was observed after hCRH (P < 0.01). The same effect occurred following TRH but was less striking (P = 0.05). hCRH and TRH caused a reduction in the CO2 threshold. The CO2-response curves in the control group were nearly identical. The results indicate an additive effect of both releasing hormones on the hypercapnic ventilatory response in humans, presumably independent of central chemosensitivity.","[{'text': 'corticotropin', 'type': 'Chemical', 'start': 6, 'end': 19, 'mesh': 'D000324'}, {'text': 'thyrotropin', 'type': 'Chemical', 'start': 42, 'end': 53, 'mesh': 'D013972'}, {'text': 'hypercapnic', 'type': 'Disease', 'start': 85, 'end': 96, 'mesh': 'D006935'}, {'text': 'corticotropin', 'type': 'Chemical', 'start': 135, 'end': 148, 'mesh': 'D000324'}, {'text': 'thyrotropin', 'type': 'Chemical', 'start': 178, 'end': 189, 'mesh': 'D013972'}, {'text': 'CO2', 'type': 'Chemical', 'start': 424, 'end': 427, 'mesh': 'D002245'}, {'text': 'NaCl', 'type': 'Chemical', 'start': 517, 'end': 521, 'mesh': 'D012965'}, {'text': 'NaCl', 'type': 'Chemical', 'start': 676, 'end': 680, 'mesh': 'D012965'}, {'text': 'CO2', 'type': 'Chemical', 'start': 726, 'end': 729, 'mesh': 'D002245'}, {'text': 'CO2', 'type': 'Chemical', 'start': 852, 'end': 855, 'mesh': 'D002245'}, {'text': 'CO2', 'type': 'Chemical', 'start': 1031, 'end': 1034, 'mesh': 'D002245'}, {'text': 'CO2', 'type': 'Chemical', 'start': 1050, 'end': 1053, 'mesh': 'D002245'}, {'text': 'hypercapnic', 'type': 'Disease', 'start': 1188, 'end': 1199, 'mesh': 'D006935'}]"
+1296,8985298,Lamivudine is effective in suppressing hepatitis B virus DNA in Chinese hepatitis B surface antigen carriers: a placebo-controlled trial.,"Lamivudine is a novel 2',3'-dideoxy cytosine analogue that has potent inhibitory effects on hepatitis B virus replication in vitro and in vivo. We performed a single-blind, placebo-controlled study to assess its effectiveness and safety in Chinese hepatitis B surface antigen (HBsAg) carriers. Forty-two Chinese HBsAg carriers were randomized to receive placebo (6 patients) or lamivudine orally in dosages of 25 mg, 100 mg, or 300 mg daily (12 patients for each dosage). The drug was given for 4 weeks. The patients were closely monitored clinically, biochemically, and serologically up to 4 weeks after drug treatment. All 36 patients receiving lamivudine had a decrease in hepatitis B virus (HBV) DNA values of >90% (P < .001 compared with placebo). Although 25 mg of lamivudine was slightly less effective than 100 mg (P = .011) and 300 mg (P = .005), it still induced 94% suppression of HBV DNA after the fourth week of therapy. HBV DNA values returned to pretreatment levels within 4 weeks of cessation of therapy. There was no change in the hepatitis B e antigen status or in aminotransferase levels. No serious adverse events were observed. In conclusion, a 4-week course of lamivudine was safe and effective in suppression of HBV DNA in Chinese HBsAg carriers. The suppression was >90% but reversible. Studies with long-term lamivudine administration should be performed to determine if prolonged suppression of HBV DNA can be achieved.","[{'text': 'Lamivudine', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D019259'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 39, 'end': 50, 'mesh': 'D006509'}, {'text': 'hepatitis B surface antigen', 'type': 'Chemical', 'start': 72, 'end': 99, 'mesh': 'D006514'}, {'text': 'Lamivudine', 'type': 'Chemical', 'start': 138, 'end': 148, 'mesh': 'D019259'}, {'text': ""2',3'-dideoxy cytosine"", 'type': 'Chemical', 'start': 160, 'end': 182, 'mesh': 'D019259'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 230, 'end': 241, 'mesh': 'D006509'}, {'text': 'hepatitis B surface antigen', 'type': 'Chemical', 'start': 386, 'end': 413, 'mesh': 'D006514'}, {'text': 'HBsAg', 'type': 'Chemical', 'start': 415, 'end': 420, 'mesh': 'D006514'}, {'text': 'HBsAg', 'type': 'Chemical', 'start': 450, 'end': 455, 'mesh': 'D006514'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 516, 'end': 526, 'mesh': 'D019259'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 785, 'end': 795, 'mesh': 'D019259'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 814, 'end': 825, 'mesh': 'D006509'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 909, 'end': 919, 'mesh': 'D019259'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 1186, 'end': 1197, 'mesh': 'D006509'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 1321, 'end': 1331, 'mesh': 'D019259'}, {'text': 'HBsAg', 'type': 'Chemical', 'start': 1392, 'end': 1397, 'mesh': 'D006514'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 1472, 'end': 1482, 'mesh': 'D019259'}]"
+1297,8996419,Population-based study of risk of venous thromboembolism associated with various oral contraceptives.,"BACKGROUND: Four studies published since December, 1995, reported that the incidence of venous thromboembolism (VTE) was higher in women who used oral contraceptives (OCs) containing the third-generation progestagens gestodene or desogestrel than in users of OCs containing second-generation progestagens. However, confounding and bias in the design of these studies may have affected the findings. The aim of our study was to re-examine the association between risk of VTE and OC use with a different study design and analysis to avoid some of the bias and confounding of the earlier studies. METHODS: We used computer records of patients from 143 general practices in the UK. The study was based on the medical records of about 540,000 women born between 1941 and 1981. All women who had a recorded diagnosis of deep-vein thrombosis, venous thrombosis not otherwise specified, or pulmonary embolus during the study period, and who had been treated with an anticoagulant were identified as potential cases of VTE. We did a cohort analysis to estimate and compare incidence of VTE in users of the main OC preparations, and a nested case-control study to calculate the odds ratios of VTE associated with use of different types of OC, after adjustment for potential confounding factors. In the case-control study, we matched cases to controls by exact year of birth, practice, and current use of OCs. We used a multiple logistic regression model that included body-mass index, number of cycles, change in type of OC prescribed within 3 months of the event, previous pregnancy, and concurrent disease. FINDINGS: 85 women met the inclusion criteria for VTE, two of whom were users of progestagen-only OCs. Of the 83 cases of VTE associated with use of combined OCs, 43 were recorded as deep-vein thrombosis, 35 as pulmonary thrombosis, and five as venous thrombosis not otherwise specified. The crude rate of VTE per 10,000 woman-years was 4.10 in current users of any OC, 3.10 in users of second-generation OCs, and 4.96 in users of third-generation preparations. After adjustment for age, the rate ratio of VTE in users of third-generation relative to second-generation OCs was 1.68 (95% CI 1.04-2.75). Logistic regression showed no significant difference in the risk of VTE between users of third-generation and second-generation OCs. Among users of third-generation progestagens, the risk of VTE was higher in users of desogestrel with 20 g ethinyloestradiol than in users of gestodene or desogestrel with 30 g ethinyloestradiol. With all second-generation OCs as the reference, the odds ratios for VTE were 3.49 (1.21-10.12) for desogestrel plus 20 g ethinyloestradiol and 1.18 (0.66-2.17) for the other third-generation progestagens. INTERPRETATION: The previously reported increase in odds ratio associated with third-generation OCs when compared with second-generation products is likely to have been the result of residual confounding by age. The increased odds ratio associated with products containing 20 micrograms ethinyloestradiol and desogestrel compared with the 30 micrograms product is biologically implausible, and is likely to be the result of preferential prescribing and, thus, confounding.","[{'text': 'venous thromboembolism', 'type': 'Disease', 'start': 34, 'end': 56, 'mesh': 'D054556'}, {'text': 'oral contraceptives', 'type': 'Chemical', 'start': 81, 'end': 100, 'mesh': 'D003276'}, {'text': 'venous thromboembolism', 'type': 'Disease', 'start': 190, 'end': 212, 'mesh': 'D054556'}, {'text': 'VTE', 'type': 'Disease', 'start': 214, 'end': 217, 'mesh': 'D054556'}, {'text': 'oral contraceptives', 'type': 'Chemical', 'start': 248, 'end': 267, 'mesh': 'D003276'}, {'text': 'OCs', 'type': 'Chemical', 'start': 269, 'end': 272, 'mesh': 'D003276'}, {'text': 'progestagens', 'type': 'Chemical', 'start': 306, 'end': 318, 'mesh': 'D011374'}, {'text': 'gestodene', 'type': 'Chemical', 'start': 319, 'end': 328, 'mesh': 'C033273'}, {'text': 'desogestrel', 'type': 'Chemical', 'start': 332, 'end': 343, 'mesh': 'D017135'}, {'text': 'OCs', 'type': 'Chemical', 'start': 361, 'end': 364, 'mesh': 'D003276'}, {'text': 'progestagens', 'type': 'Chemical', 'start': 394, 'end': 406, 'mesh': 'D011374'}, {'text': 'VTE', 'type': 'Disease', 'start': 572, 'end': 575, 'mesh': 'D054556'}, {'text': 'OC', 'type': 'Chemical', 'start': 580, 'end': 582, 'mesh': 'D003276'}, {'text': 'deep-vein thrombosis', 'type': 'Disease', 'start': 916, 'end': 936, 'mesh': 'D020246'}, {'text': 'venous thrombosis', 'type': 'Disease', 'start': 938, 'end': 955, 'mesh': 'D020246'}, {'text': 'VTE', 'type': 'Disease', 'start': 1112, 'end': 1115, 'mesh': 'D054556'}, {'text': 'VTE', 'type': 'Disease', 'start': 1179, 'end': 1182, 'mesh': 'D054556'}, {'text': 'OC', 'type': 'Chemical', 'start': 1204, 'end': 1206, 'mesh': 'D003276'}, {'text': 'VTE', 'type': 'Disease', 'start': 1285, 'end': 1288, 'mesh': 'D054556'}, {'text': 'OC', 'type': 'Chemical', 'start': 1331, 'end': 1333, 'mesh': 'D003276'}, {'text': 'OCs', 'type': 'Chemical', 'start': 1496, 'end': 1499, 'mesh': 'D003276'}, {'text': 'OC', 'type': 'Chemical', 'start': 1613, 'end': 1615, 'mesh': 'D003276'}, {'text': 'VTE', 'type': 'Disease', 'start': 1751, 'end': 1754, 'mesh': 'D054556'}, {'text': 'progestagen', 'type': 'Chemical', 'start': 1782, 'end': 1793, 'mesh': 'D011372'}, {'text': 'OCs', 'type': 'Chemical', 'start': 1799, 'end': 1802, 'mesh': 'D003276'}, {'text': 'VTE', 'type': 'Disease', 'start': 1823, 'end': 1826, 'mesh': 'D054556'}, {'text': 'OCs', 'type': 'Chemical', 'start': 1859, 'end': 1862, 'mesh': 'D003276'}, {'text': 'deep-vein thrombosis', 'type': 'Disease', 'start': 1884, 'end': 1904, 'mesh': 'D020246'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 1922, 'end': 1932, 'mesh': 'D013927'}, {'text': 'venous thrombosis', 'type': 'Disease', 'start': 1946, 'end': 1963, 'mesh': 'D020246'}, {'text': 'VTE', 'type': 'Disease', 'start': 2007, 'end': 2010, 'mesh': 'D054556'}, {'text': 'OC', 'type': 'Chemical', 'start': 2067, 'end': 2069, 'mesh': 'D003276'}, {'text': 'OCs', 'type': 'Chemical', 'start': 2106, 'end': 2109, 'mesh': 'D003276'}, {'text': 'VTE', 'type': 'Disease', 'start': 2207, 'end': 2210, 'mesh': 'D054556'}, {'text': 'OCs', 'type': 'Chemical', 'start': 2270, 'end': 2273, 'mesh': 'D003276'}, {'text': 'VTE', 'type': 'Disease', 'start': 2371, 'end': 2374, 'mesh': 'D054556'}, {'text': 'OCs', 'type': 'Chemical', 'start': 2431, 'end': 2434, 'mesh': 'D003276'}, {'text': 'progestagens', 'type': 'Chemical', 'start': 2468, 'end': 2480, 'mesh': 'D011374'}, {'text': 'VTE', 'type': 'Disease', 'start': 2494, 'end': 2497, 'mesh': 'D054556'}, {'text': 'desogestrel', 'type': 'Chemical', 'start': 2521, 'end': 2532, 'mesh': 'D017135'}, {'text': 'ethinyloestradiol', 'type': 'Chemical', 'start': 2543, 'end': 2560, 'mesh': 'D004997'}, {'text': 'gestodene', 'type': 'Chemical', 'start': 2578, 'end': 2587, 'mesh': 'C033273'}, {'text': 'desogestrel', 'type': 'Chemical', 'start': 2591, 'end': 2602, 'mesh': 'D017135'}, {'text': 'ethinyloestradiol', 'type': 'Chemical', 'start': 2613, 'end': 2630, 'mesh': 'D004997'}, {'text': 'OCs', 'type': 'Chemical', 'start': 2659, 'end': 2662, 'mesh': 'D003276'}, {'text': 'VTE', 'type': 'Disease', 'start': 2701, 'end': 2704, 'mesh': 'D054556'}, {'text': 'desogestrel', 'type': 'Chemical', 'start': 2732, 'end': 2743, 'mesh': 'D017135'}, {'text': 'ethinyloestradiol', 'type': 'Chemical', 'start': 2754, 'end': 2771, 'mesh': 'D004997'}, {'text': 'progestagens', 'type': 'Chemical', 'start': 2824, 'end': 2836, 'mesh': 'D011374'}, {'text': 'OCs', 'type': 'Chemical', 'start': 2934, 'end': 2937, 'mesh': 'D003276'}, {'text': 'ethinyloestradiol', 'type': 'Chemical', 'start': 3125, 'end': 3142, 'mesh': 'D004997'}, {'text': 'desogestrel', 'type': 'Chemical', 'start': 3147, 'end': 3158, 'mesh': 'D017135'}]"
+1298,9061777,MK-801 augments pilocarpine-induced electrographic seizure but protects against brain damage in rats.,"1. The authors examined the anticonvulsant effects of MK-801 on the pilocarpine-induced seizure model. Intraperitoneal injection of pilocarpine (400 mg/kg) induced tonic and clonic seizure. Scopolamine (10 mg/kg) and pentobarbital (5 mg/kg) prevented development of pilocarpine-induced behavioral seizure but MK-801 (0.5 mg/kg) did not. 2. An electrical seizure measured with hippocampal EEG appeared in the pilocarpine-treated group. Scopolamine and pentobarbital blocked the pilocarpine-induced electrographic seizure, MK-801 treatment augmented the electrographic seizure induced by pilocarpine. 3. Brain damage was assessed by examining the hippocampus microscopically. Pilocarpine produced neuronal death in the hippocampus, which showed pyknotic changes. Pentobarbital, scopolamine and MK-801 protected the brain damage by pilocarpine, though in the MK-801-treated group, the pyramidal cells of hippocampus appeared darker than normal. In all treatments, granule cells of the dentate gyrus were not affected. 4. These results indicate that status epilepticus induced by pilocarpine is initiated by cholinergic overstimulation and propagated by glutamatergic transmission, the elevation of which may cause brain damage through an excitatory NMDA receptor-mediated mechanism.","[{'text': 'MK-801', 'type': 'Chemical', 'start': 0, 'end': 6, 'mesh': 'D016291'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 16, 'end': 27, 'mesh': 'D010862'}, {'text': 'seizure', 'type': 'Disease', 'start': 51, 'end': 58, 'mesh': 'D012640'}, {'text': 'brain damage', 'type': 'Disease', 'start': 80, 'end': 92, 'mesh': 'D001930'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 156, 'end': 162, 'mesh': 'D016291'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 170, 'end': 181, 'mesh': 'D010862'}, {'text': 'seizure', 'type': 'Disease', 'start': 190, 'end': 197, 'mesh': 'D012640'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 234, 'end': 245, 'mesh': 'D010862'}, {'text': 'tonic and clonic seizure', 'type': 'Disease', 'start': 266, 'end': 290, 'mesh': 'D012640'}, {'text': 'Scopolamine', 'type': 'Chemical', 'start': 292, 'end': 303, 'mesh': 'D012601'}, {'text': 'pentobarbital', 'type': 'Chemical', 'start': 319, 'end': 332, 'mesh': 'D010424'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 368, 'end': 379, 'mesh': 'D010862'}, {'text': 'seizure', 'type': 'Disease', 'start': 399, 'end': 406, 'mesh': 'D012640'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 411, 'end': 417, 'mesh': 'D016291'}, {'text': 'seizure', 'type': 'Disease', 'start': 456, 'end': 463, 'mesh': 'D012640'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 510, 'end': 521, 'mesh': 'D010862'}, {'text': 'Scopolamine', 'type': 'Chemical', 'start': 537, 'end': 548, 'mesh': 'D012601'}, {'text': 'pentobarbital', 'type': 'Chemical', 'start': 553, 'end': 566, 'mesh': 'D010424'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 579, 'end': 590, 'mesh': 'D010862'}, {'text': 'seizure', 'type': 'Disease', 'start': 614, 'end': 621, 'mesh': 'D012640'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 623, 'end': 629, 'mesh': 'D016291'}, {'text': 'seizure', 'type': 'Disease', 'start': 669, 'end': 676, 'mesh': 'D012640'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 688, 'end': 699, 'mesh': 'D010862'}, {'text': 'Brain damage', 'type': 'Disease', 'start': 704, 'end': 716, 'mesh': 'D001930'}, {'text': 'Pilocarpine', 'type': 'Chemical', 'start': 776, 'end': 787, 'mesh': 'D010862'}, {'text': 'neuronal death', 'type': 'Disease', 'start': 797, 'end': 811, 'mesh': 'D009410'}, {'text': 'Pentobarbital', 'type': 'Chemical', 'start': 863, 'end': 876, 'mesh': 'D010424'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 878, 'end': 889, 'mesh': 'D012601'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 894, 'end': 900, 'mesh': 'D016291'}, {'text': 'brain damage', 'type': 'Disease', 'start': 915, 'end': 927, 'mesh': 'D001930'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 931, 'end': 942, 'mesh': 'D010862'}, {'text': 'MK-801', 'type': 'Chemical', 'start': 958, 'end': 964, 'mesh': 'D016291'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 1148, 'end': 1166, 'mesh': 'D013226'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1178, 'end': 1189, 'mesh': 'D010862'}, {'text': 'brain damage', 'type': 'Disease', 'start': 1313, 'end': 1325, 'mesh': 'D001930'}, {'text': 'NMDA', 'type': 'Chemical', 'start': 1348, 'end': 1352, 'mesh': 'D016202'}]"
+1299,9071336,"Paclitaxel, 5-fluorouracil, and folinic acid in metastatic breast cancer: BRE-26, a phase II trial.","5-Fluorouracil plus folinic acid and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) are effective salvage therapies for metastatic breast cancer patients. Paclitaxel and 5-fluorouracil have additive cytotoxicity in MCF-7 cell lines. We performed a phase II trial of paclitaxel 175 mg/m2 over 3 hours on day I followed by folinic acid 300 mg over 1 hour before 5-fluorouracil 350 mg/m2 on days 1 to 3 every 28 days (TFL) in women with metastatic breast cancer. Analysis is reported on 37 patients with a minimum of 6 months follow-up who received a total of 192 cycles of TFL: nine cycles (5%) were associated with grade 3/4 neutropenia requiring hospitalization; seven (4%) cycles in two patients required granulocyte colony-stimulating factor due to neutropenia; no patient required platelet transfusions. Grade 3/4 nonhematologic toxicities were uncommon. Among the 34 patients evaluable for response, there were three complete responses (9%) and 18 partial responses (53%) for an overall response rate of 62%. Of the 19 evaluable patients with prior doxorubicin exposure, 11 (58%) responded compared with nine of 15 (60%) without prior doxorubicin. Plasma paclitaxel concentrations were measured at the completion of paclitaxel infusion and at 24 hours in 19 patients. TFL is an active, well-tolerated regimen in metastatic breast cancer.","[{'text': 'Paclitaxel', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D017239'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 12, 'end': 26, 'mesh': 'D005472'}, {'text': 'folinic acid', 'type': 'Chemical', 'start': 32, 'end': 44, 'mesh': 'D002955'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 59, 'end': 72, 'mesh': 'D001943'}, {'text': '5-Fluorouracil', 'type': 'Chemical', 'start': 100, 'end': 114, 'mesh': 'D005472'}, {'text': 'folinic acid', 'type': 'Chemical', 'start': 120, 'end': 132, 'mesh': 'D002955'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 137, 'end': 147, 'mesh': 'D017239'}, {'text': 'Taxol', 'type': 'Chemical', 'start': 149, 'end': 154, 'mesh': 'D017239'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 248, 'end': 261, 'mesh': 'D001943'}, {'text': 'Paclitaxel', 'type': 'Chemical', 'start': 272, 'end': 282, 'mesh': 'D017239'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 287, 'end': 301, 'mesh': 'D005472'}, {'text': 'cytotoxicity', 'type': 'Disease', 'start': 316, 'end': 328, 'mesh': 'D064420'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 383, 'end': 393, 'mesh': 'D017239'}, {'text': 'folinic acid', 'type': 'Chemical', 'start': 438, 'end': 450, 'mesh': 'D002955'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 477, 'end': 491, 'mesh': 'D005472'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 562, 'end': 575, 'mesh': 'D001943'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 741, 'end': 752, 'mesh': 'D009503'}, {'text': 'granulocyte colony-stimulating factor', 'type': 'Chemical', 'start': 823, 'end': 860, 'mesh': 'D016179'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 868, 'end': 879, 'mesh': 'D009503'}, {'text': 'toxicities', 'type': 'Disease', 'start': 949, 'end': 959, 'mesh': 'D064420'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1170, 'end': 1181, 'mesh': 'D004317'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1256, 'end': 1267, 'mesh': 'D004317'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 1276, 'end': 1286, 'mesh': 'D017239'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 1337, 'end': 1347, 'mesh': 'D017239'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 1444, 'end': 1457, 'mesh': 'D001943'}]"
+1300,9125676,"Efficacy and proarrhythmia with the use of d,l-sotalol for sustained ventricular tachyarrhythmias.","This study prospectively evaluated the clinical efficacy, the incidence of torsades de pointes, and the presumable risk factors for torsades de pointes in patients treated with d,l-sotalol for sustained ventricular tachyarrhythmias. Eighty-one consecutive patients (54 with coronary artery disease, and 20 with dilated cardiomyopathy) with inducible sustained ventricular tachycardia or ventricular fibrillation received oral d,l-sotalol to prevent induction of the ventricular tachyarrhythmia. During oral loading with d,l-sotalol, continuous electrocardiographic (ECG) monitoring was performed. Those patients in whom d,l-sotalol prevented induction of ventricular tachycardia or ventricular fibrillation were discharged with the drug and followed up on an outpatient basis for 21 +/- 18 months. Induction of the ventricular tachyarrhythmia was prevented by oral d,l-sotalol in 35 (43%) patients; the ventricular tachyarrhythmia remained inducible in 40 (49%) patients; and two (2.5%) patients did not tolerate even 40 mg of d,l-sotalol once daily. Four (5%) patients had from torsades de pointes during the initial oral treatment with d,l-sotalol. Neither ECG [sinus-cycle length (SCL), QT or QTc interval, or U wave] nor clinical parameters identified patients at risk for torsades de pointes. However, the oral dose of d,l-sotalol was significantly lower in patients with torsades de pointes (200 +/- 46 vs. 328 +/- 53 mg/day; p = 0.0017). Risk factors associated with the development of torsades de pointes were the appearance of an U wave (p = 0.049), female gender (p = 0.015), and significant dose-corrected changes of SCL, QT interval, and QTc interval (p < 0.05). During follow-up, seven (20%) patients had a nonfatal ventricular tachycardia recurrence, and two (6%) patients died suddenly. One female patient with stable cardiac disease had recurrent torsades de pointes after 2 years of successful treatment with d,l-sotalol. Torsades de pointes occurred early during treatment even with low doses of oral d,l-sotalol. Pronounced changes in the surface ECG (cycle length, QT, and QTc) in relation to the dose of oral d,l-sotalol might identify a subgroup of patients with an increased risk for torsades de pointes. Other ECG parameters before the application of d,l-sotalol did not identify patients at increased risk for torsades de pointes. Recurrence rates of ventricular tachyarrhythmias are high despite complete suppression of the arrhythmia during programmed stimulation. Therefore programmed electrical stimulation in the case of d,l-sotalol seems to be of limited prognostic value.","[{'text': 'proarrhythmia', 'type': 'Disease', 'start': 13, 'end': 26, 'mesh': '-1'}, {'text': 'd,l-sotalol', 'type': 'Chemical', 'start': 43, 'end': 54, 'mesh': 'D013015'}, {'text': 'ventricular tachyarrhythmias', 'type': 'Disease', 'start': 69, 'end': 97, 'mesh': 'D017180'}, {'text': 'torsades de pointes', 'type': 'Disease', 'start': 174, 'end': 193, 'mesh': 'D016171'}, {'text': 'torsades de pointes', 'type': 'Disease', 'start': 231, 'end': 250, 'mesh': 'D016171'}, {'text': 'd,l-sotalol', 'type': 'Chemical', 'start': 276, 'end': 287, 'mesh': 'D013015'}, {'text': 'ventricular tachyarrhythmias', 'type': 'Disease', 'start': 302, 'end': 330, 'mesh': 'D017180'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 373, 'end': 396, 'mesh': 'D003324'}, {'text': 'dilated cardiomyopathy', 'type': 'Disease', 'start': 410, 'end': 432, 'mesh': 'D002311'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 459, 'end': 482, 'mesh': 'D017180'}, {'text': 'ventricular fibrillation', 'type': 'Disease', 'start': 486, 'end': 510, 'mesh': 'D014693'}, {'text': 'd,l-sotalol', 'type': 'Chemical', 'start': 525, 'end': 536, 'mesh': 'D013015'}, {'text': 'ventricular tachyarrhythmia', 'type': 'Disease', 'start': 565, 'end': 592, 'mesh': 'D017180'}, {'text': 'd,l-sotalol', 'type': 'Chemical', 'start': 619, 'end': 630, 'mesh': 'D013015'}, {'text': 'd,l-sotalol', 'type': 'Chemical', 'start': 719, 'end': 730, 'mesh': 'D013015'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 754, 'end': 777, 'mesh': 'D017180'}, {'text': 'ventricular fibrillation', 'type': 'Disease', 'start': 781, 'end': 805, 'mesh': 'D014693'}, {'text': 'ventricular tachyarrhythmia', 'type': 'Disease', 'start': 914, 'end': 941, 'mesh': 'D017180'}, {'text': 'd,l-sotalol', 'type': 'Chemical', 'start': 964, 'end': 975, 'mesh': 'D013015'}, {'text': 'ventricular tachyarrhythmia', 'type': 'Disease', 'start': 1002, 'end': 1029, 'mesh': 'D017180'}, {'text': 'd,l-sotalol', 'type': 'Chemical', 'start': 1126, 'end': 1137, 'mesh': 'D013015'}, {'text': 'torsades de pointes', 'type': 'Disease', 'start': 1178, 'end': 1197, 'mesh': 'D016171'}, {'text': 'd,l-sotalol', 'type': 'Chemical', 'start': 1237, 'end': 1248, 'mesh': 'D013015'}, {'text': 'torsades de pointes', 'type': 'Disease', 'start': 1376, 'end': 1395, 'mesh': 'D016171'}, {'text': 'd,l-sotalol', 'type': 'Chemical', 'start': 1423, 'end': 1434, 'mesh': 'D013015'}, {'text': 'torsades de pointes', 'type': 'Disease', 'start': 1476, 'end': 1495, 'mesh': 'D016171'}, {'text': 'torsades de pointes', 'type': 'Disease', 'start': 1592, 'end': 1611, 'mesh': 'D016171'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 1828, 'end': 1851, 'mesh': 'D017180'}, {'text': 'cardiac disease', 'type': 'Disease', 'start': 1932, 'end': 1947, 'mesh': 'D006331'}, {'text': 'torsades de pointes', 'type': 'Disease', 'start': 1962, 'end': 1981, 'mesh': 'D016171'}, {'text': 'd,l-sotalol', 'type': 'Chemical', 'start': 2025, 'end': 2036, 'mesh': 'D013015'}, {'text': 'Torsades de pointes', 'type': 'Disease', 'start': 2038, 'end': 2057, 'mesh': 'D016171'}, {'text': 'd,l-sotalol', 'type': 'Chemical', 'start': 2118, 'end': 2129, 'mesh': 'D013015'}, {'text': 'd,l-sotalol', 'type': 'Chemical', 'start': 2229, 'end': 2240, 'mesh': 'D013015'}, {'text': 'torsades de pointes', 'type': 'Disease', 'start': 2306, 'end': 2325, 'mesh': 'D016171'}, {'text': 'd,l-sotalol', 'type': 'Chemical', 'start': 2374, 'end': 2385, 'mesh': 'D013015'}, {'text': 'torsades de pointes', 'type': 'Disease', 'start': 2434, 'end': 2453, 'mesh': 'D016171'}, {'text': 'ventricular tachyarrhythmias', 'type': 'Disease', 'start': 2475, 'end': 2503, 'mesh': 'D017180'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 2549, 'end': 2559, 'mesh': 'D001145'}, {'text': 'd,l-sotalol', 'type': 'Chemical', 'start': 2650, 'end': 2661, 'mesh': 'D013015'}]"
+1301,9128918,Chronic hyperprolactinemia and changes in dopamine neurons.,"The tuberoinfundibular dopaminergic (TIDA) system is known to inhibit prolactin (PRL) secretion. In young animals this system responds to acute elevations in serum PRL by increasing its activity. However, this responsiveness is lost in aging rats with chronically high serum PRL levels. The purpose of this study was to induce hyperprolactinemia in rats for extended periods of time and examine its effects on dopaminergic systems in the brain. Hyperprolactinemia was induced by treatment with haloperidol, a dopamine receptor antagonist, and Palkovits' microdissection technique in combination with high-performance liquid chromatography was used to measure neurotransmitter concentrations in several areas of the brain. After 6 months of hyperprolactinemia, dopamine (DA) concentrations in the median eminence (ME) increased by 84% over the control group. Nine months of hyperprolactinemia produced a 50% increase in DA concentrations in the ME over the control group. However, DA response was lost if a 9-month long haloperidol-induced hyperprolactinemia was followed by a 1 1/2 month-long extremely high increase in serum PRL levels produced by implantation of MMQ cells under the kidney capsule. There was no change in the levels of DA, norepinephrine (NE), serotonin (5-HT), or their metabolites in the arcuate nucleus (AN), medial preoptic area (MPA), caudate putamen (CP), substantia nigra (SN), and zona incerta (ZI), except for a decrease in 5-hydroxyindoleacetic acid (5-HIAA) in the AN after 6-months of hyperprolactinemia and an increase in DA concentrations in the AN after 9-months of hyperprolactinemia. These results demonstrate that hyperprolactinemia specifically affects TIDA neurons and these effects vary, depending on the duration and intensity of hyperprolactinemia. The age-related decrease in hypothalamic dopamine function may be associated with increases in PRL secretion.","[{'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 8, 'end': 26, 'mesh': 'D006966'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 42, 'end': 50, 'mesh': 'D004298'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 387, 'end': 405, 'mesh': 'D006966'}, {'text': 'Hyperprolactinemia', 'type': 'Disease', 'start': 505, 'end': 523, 'mesh': 'D006966'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 554, 'end': 565, 'mesh': 'D006220'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 569, 'end': 577, 'mesh': 'D004298'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 800, 'end': 818, 'mesh': 'D006966'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 820, 'end': 828, 'mesh': 'D004298'}, {'text': 'DA', 'type': 'Chemical', 'start': 830, 'end': 832, 'mesh': 'D004298'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 933, 'end': 951, 'mesh': 'D006966'}, {'text': 'DA', 'type': 'Chemical', 'start': 979, 'end': 981, 'mesh': 'D004298'}, {'text': 'DA', 'type': 'Chemical', 'start': 1040, 'end': 1042, 'mesh': 'D004298'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1079, 'end': 1090, 'mesh': 'D006220'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 1099, 'end': 1117, 'mesh': 'D006966'}, {'text': 'DA', 'type': 'Chemical', 'start': 1298, 'end': 1300, 'mesh': 'D004298'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 1302, 'end': 1316, 'mesh': 'D009638'}, {'text': 'NE', 'type': 'Chemical', 'start': 1318, 'end': 1320, 'mesh': 'D009638'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 1323, 'end': 1332, 'mesh': 'D012701'}, {'text': '5-HT', 'type': 'Chemical', 'start': 1334, 'end': 1338, 'mesh': 'D012701'}, {'text': '5-hydroxyindoleacetic acid', 'type': 'Chemical', 'start': 1512, 'end': 1538, 'mesh': 'D006897'}, {'text': '5-HIAA', 'type': 'Chemical', 'start': 1540, 'end': 1546, 'mesh': 'D006897'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 1576, 'end': 1594, 'mesh': 'D006966'}, {'text': 'DA', 'type': 'Chemical', 'start': 1614, 'end': 1616, 'mesh': 'D004298'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 1660, 'end': 1678, 'mesh': 'D006966'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 1711, 'end': 1729, 'mesh': 'D006966'}, {'text': 'hyperprolactinemia', 'type': 'Disease', 'start': 1831, 'end': 1849, 'mesh': 'D006966'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1892, 'end': 1900, 'mesh': 'D004298'}]"
+1302,9132810,Treatment-related disseminated necrotizing leukoencephalopathy with characteristic contrast enhancement of the white matter.,"This report describes unique contrast enhancement of the white matter on T1-weighted magnetic resonance images of two patients with disseminated necrotizing leukoencephalopathy, which developed from acute lymphoblastic leukemia treated with high-dose methotrexate. In both patients, the enhancement was more pronounced near the base of the brain than at the vertex. Necropsy of the first case revealed loss of myelination and necrosis of the white matter. Possible mechanisms causing such a leukoencephalopathy are discussed.","[{'text': 'leukoencephalopathy', 'type': 'Disease', 'start': 43, 'end': 62, 'mesh': 'D056784'}, {'text': 'leukoencephalopathy', 'type': 'Disease', 'start': 282, 'end': 301, 'mesh': 'D056784'}, {'text': 'acute lymphoblastic leukemia', 'type': 'Disease', 'start': 324, 'end': 352, 'mesh': 'D054198'}, {'text': 'methotrexate', 'type': 'Chemical', 'start': 376, 'end': 388, 'mesh': 'D008727'}, {'text': 'loss of myelination', 'type': 'Disease', 'start': 527, 'end': 546, 'mesh': 'D003711'}, {'text': 'necrosis', 'type': 'Disease', 'start': 551, 'end': 559, 'mesh': 'D009336'}, {'text': 'leukoencephalopathy', 'type': 'Disease', 'start': 616, 'end': 635, 'mesh': 'D056784'}]"
+1303,9158667,Thrombotic complications in acute promyelocytic leukemia during all-trans-retinoic acid therapy.,"A case of acute renal failure, due to occlusion of renal vessels in a patient with acute promyelocytic leukemia (APL) treated with all-trans-retinoic acid (ATRA) and tranexamic acid has been described recently. We report a case of acute renal failure in an APL patient treated with ATRA alone. This case further supports the concern about thromboembolic complications associated with ATRA therapy in APL patients. The patients, a 43-year-old man, presented all the signs and symptoms of APL and was included in a treatment protocol with ATRA. After 10 days of treatment, he developed acute renal failure that was completely reversible after complete remission of APL was achieved and therapy discontinued. We conclude that ATRA is a valid therapeutic choice for patients with APL, although the procoagulant tendency is not completely corrected. Thrombotic events, however, could be avoided by using low-dose heparin.","[{'text': 'Thrombotic', 'type': 'Disease', 'start': 0, 'end': 10, 'mesh': 'D013927'}, {'text': 'acute promyelocytic leukemia', 'type': 'Disease', 'start': 28, 'end': 56, 'mesh': 'D015473'}, {'text': 'all-trans-retinoic acid', 'type': 'Chemical', 'start': 64, 'end': 87, 'mesh': 'D014212'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 107, 'end': 126, 'mesh': 'D058186'}, {'text': 'occlusion of renal vessels', 'type': 'Disease', 'start': 135, 'end': 161, 'mesh': '-1'}, {'text': 'acute promyelocytic leukemia', 'type': 'Disease', 'start': 180, 'end': 208, 'mesh': 'D015473'}, {'text': 'APL', 'type': 'Disease', 'start': 210, 'end': 213, 'mesh': 'D015473'}, {'text': 'all-trans-retinoic acid', 'type': 'Chemical', 'start': 228, 'end': 251, 'mesh': 'D014212'}, {'text': 'ATRA', 'type': 'Chemical', 'start': 253, 'end': 257, 'mesh': 'D014212'}, {'text': 'tranexamic acid', 'type': 'Chemical', 'start': 263, 'end': 278, 'mesh': 'D014148'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 328, 'end': 347, 'mesh': 'D058186'}, {'text': 'APL', 'type': 'Disease', 'start': 354, 'end': 357, 'mesh': 'D015473'}, {'text': 'ATRA', 'type': 'Chemical', 'start': 379, 'end': 383, 'mesh': 'D014212'}, {'text': 'thromboembolic', 'type': 'Disease', 'start': 436, 'end': 450, 'mesh': 'D013923'}, {'text': 'ATRA', 'type': 'Chemical', 'start': 481, 'end': 485, 'mesh': 'D014212'}, {'text': 'APL', 'type': 'Disease', 'start': 497, 'end': 500, 'mesh': 'D015473'}, {'text': 'APL', 'type': 'Disease', 'start': 584, 'end': 587, 'mesh': 'D015473'}, {'text': 'ATRA', 'type': 'Chemical', 'start': 634, 'end': 638, 'mesh': 'D014212'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 681, 'end': 700, 'mesh': 'D058186'}, {'text': 'APL', 'type': 'Disease', 'start': 760, 'end': 763, 'mesh': 'D015473'}, {'text': 'ATRA', 'type': 'Chemical', 'start': 820, 'end': 824, 'mesh': 'D014212'}, {'text': 'APL', 'type': 'Disease', 'start': 873, 'end': 876, 'mesh': 'D015473'}, {'text': 'Thrombotic', 'type': 'Disease', 'start': 942, 'end': 952, 'mesh': 'D013927'}, {'text': 'heparin', 'type': 'Chemical', 'start': 1005, 'end': 1012, 'mesh': 'D006493'}]"
+1304,9197951,Pupillary changes associated with the development of stimulant-induced mania: a case report.,"A 30-year-old cocaine-dependent man who was a subject in a study evaluating the anticraving efficacy of the stimulant medication diethylpropion (DEP) became manic during his second week on the study drug. Pupillometric changes while on DEP, especially changes in the total power of pupillary oscillation, were dramatically different than those observed in the eight other study subjects who did not become manic. The large changes in total power of pupillary oscillation occurred a few days before the patient became fully manic. Such medication-associated changes in the total power of pupillary oscillation might be of utility in identifying persons at risk for manic-like adverse effects during the medical use of psychomotor stimulants or sympathomimetic agents.","[{'text': 'mania', 'type': 'Disease', 'start': 71, 'end': 76, 'mesh': 'D001714'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 107, 'end': 114, 'mesh': 'D003042'}, {'text': 'diethylpropion', 'type': 'Chemical', 'start': 222, 'end': 236, 'mesh': 'D004053'}, {'text': 'DEP', 'type': 'Chemical', 'start': 238, 'end': 241, 'mesh': 'D004053'}, {'text': 'manic', 'type': 'Disease', 'start': 250, 'end': 255, 'mesh': 'D001714'}, {'text': 'DEP', 'type': 'Chemical', 'start': 329, 'end': 332, 'mesh': 'D004053'}, {'text': 'pupillary oscillation', 'type': 'Disease', 'start': 375, 'end': 396, 'mesh': 'D011681'}, {'text': 'manic', 'type': 'Disease', 'start': 499, 'end': 504, 'mesh': 'D001714'}, {'text': 'pupillary oscillation', 'type': 'Disease', 'start': 542, 'end': 563, 'mesh': 'D011681'}, {'text': 'manic', 'type': 'Disease', 'start': 616, 'end': 621, 'mesh': 'D001714'}, {'text': 'pupillary oscillation', 'type': 'Disease', 'start': 680, 'end': 701, 'mesh': 'D011681'}, {'text': 'manic', 'type': 'Disease', 'start': 757, 'end': 762, 'mesh': 'D001714'}]"
+1305,9272404,The negative mucosal potential: separating central and peripheral effects of NSAIDs in man.,"OBJECTIVE: We wanted to test whether assessment of both a central pain-related signal (chemo-somatosensory evoked potential, CSSEP) and a concomitantly recorded peripheral signal (negative mucosal potential, NMP) allows for separation of central and peripheral effects of NSAIDs. For this purpose, experimental conditions were created in which NSAIDs had previously been observed to produce effects on phasic and tonic pain by either central or peripheral mechanisms. METHODS: According to a double-blind, randomised, controlled, threefold cross-over design, 18 healthy subjects (11 males, 7 females; mean age 26 years) received either placebo, 400 mg ibuprofen, or 800 mg ibuprofen. Phasic pain was applied by means of short pulses of CO2 to the nasal mucosa (stimulus duration 500 ms, interval approximately 60 s), and tonic pain was induced in the nasal cavity by means of dry air of controlled temperature, humidity and flow rate (22 degrees C, 0% relative humidity, 145 ml.s-1). Both CSSEPs as central and NMPs as peripheral correlates of pain were obtained in response to the CO2 stimuli. Additionally, the subjects rated the intensity of both phasic and tonic pain by means of visual analogue scales. RESULTS: As described earlier, administration of ibuprofen was followed by a decrease in tonic pain but-relative to placebo-an increase in correlates of phasic pain, indicating a specific effect of ibuprofen on the interaction between the pain stimuli under these special experimental conditions. Based on the similar behaviour of CSSEP and NMP, it was concluded that the pharmacological process underlying this phenomenon was localised in the periphery. By means of the simultaneous recording of interrelated peripheral and central electrophysiologic correlates of nociception, it was possible to separate central and peripheral effects of an NSAID. The major advantage of this pain model is the possibility of obtaining peripheral pain-related activity directly using a non-invasive technique in humans.","[{'text': 'pain', 'type': 'Disease', 'start': 158, 'end': 162, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 511, 'end': 515, 'mesh': 'D010146'}, {'text': 'ibuprofen', 'type': 'Chemical', 'start': 744, 'end': 753, 'mesh': 'D007052'}, {'text': 'ibuprofen', 'type': 'Chemical', 'start': 765, 'end': 774, 'mesh': 'D007052'}, {'text': 'pain', 'type': 'Disease', 'start': 783, 'end': 787, 'mesh': 'D010146'}, {'text': 'CO2', 'type': 'Chemical', 'start': 828, 'end': 831, 'mesh': 'D002245'}, {'text': 'pain', 'type': 'Disease', 'start': 919, 'end': 923, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 1136, 'end': 1140, 'mesh': 'D010146'}, {'text': 'CO2', 'type': 'Chemical', 'start': 1174, 'end': 1177, 'mesh': 'D002245'}, {'text': 'pain', 'type': 'Disease', 'start': 1259, 'end': 1263, 'mesh': 'D010146'}, {'text': 'ibuprofen', 'type': 'Chemical', 'start': 1349, 'end': 1358, 'mesh': 'D007052'}, {'text': 'pain', 'type': 'Disease', 'start': 1395, 'end': 1399, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 1460, 'end': 1464, 'mesh': 'D010146'}, {'text': 'ibuprofen', 'type': 'Chemical', 'start': 1498, 'end': 1507, 'mesh': 'D007052'}, {'text': 'pain', 'type': 'Disease', 'start': 1539, 'end': 1543, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 1979, 'end': 1983, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 2033, 'end': 2037, 'mesh': 'D010146'}]"
+1306,9323412,Acute severe depression following peri-operative ondansetron.,"A 41-year-old woman with a strong history of postoperative nausea and vomiting presented for abdominal hysterectomy 3 months after a previous anaesthetic where ondansetron prophylaxis had been used. She had developed a severe acute major depression disorder almost immediately thereafter, possibly related to the use of a serotonin antagonist. Nine years before she had experienced a self-limited puerperal depressive episode. Anaesthesia with a propofol infusion and avoidance of serotonin antagonists provided a nausea-free postoperative course without exacerbation of the depression disorder.","[{'text': 'depression', 'type': 'Disease', 'start': 13, 'end': 23, 'mesh': 'D003866'}, {'text': 'ondansetron', 'type': 'Chemical', 'start': 49, 'end': 60, 'mesh': 'D017294'}, {'text': 'postoperative nausea and vomiting', 'type': 'Disease', 'start': 107, 'end': 140, 'mesh': 'D020250'}, {'text': 'ondansetron', 'type': 'Chemical', 'start': 222, 'end': 233, 'mesh': 'D017294'}, {'text': 'major depression disorder', 'type': 'Disease', 'start': 294, 'end': 319, 'mesh': 'D003865'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 384, 'end': 393, 'mesh': 'D012701'}, {'text': 'depressive episode', 'type': 'Disease', 'start': 469, 'end': 487, 'mesh': 'D003866'}, {'text': 'propofol', 'type': 'Chemical', 'start': 508, 'end': 516, 'mesh': 'D015742'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 543, 'end': 552, 'mesh': 'D012701'}, {'text': 'nausea', 'type': 'Disease', 'start': 576, 'end': 582, 'mesh': 'D009325'}, {'text': 'depression disorder', 'type': 'Disease', 'start': 637, 'end': 656, 'mesh': 'D003866'}]"
+1307,9382023,Hypertensive response during dobutamine stress echocardiography.,"Among 3,129 dobutamine stress echocardiographic studies, a hypertensive response, defined as systolic blood pressure (BP) > or = 220 mm Hg and/or diastolic BP > or = 110 mm Hg, occurred in 30 patients (1%). Patients with this response more often had a history of hypertension and had higher resting systolic and diastolic BP before dobutamine infusion.","[{'text': 'Hypertensive', 'type': 'Disease', 'start': 0, 'end': 12, 'mesh': 'D006973'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 29, 'end': 39, 'mesh': 'D004280'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 77, 'end': 87, 'mesh': 'D004280'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 124, 'end': 136, 'mesh': 'D006973'}, {'text': 'hypertension', 'type': 'Disease', 'start': 328, 'end': 340, 'mesh': 'D006973'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 397, 'end': 407, 'mesh': 'D004280'}]"
+1308,9428298,Continuously nebulized albuterol in severe exacerbations of asthma in adults: a case-controlled study.,"A retrospective, case-controlled analysis comparing patients admitted to a medical intensive care unit with severe exacerbations of asthma who received continuously nebulized albuterol (CNA) versus intermittent albuterol (INA) treatments is reported. Forty matched pairs of patients with asthma are compared. CNA was administered for a mean of 11 +/- 10 hr. The incidence of cardiac dysrhythmias was similar between groups. Symptomatic hypokalemia did not occur. CNA patients had higher heart rates during treatment, which may reflect severity of illness. The incidence of intubation was similar. We conclude that CNA and INA demonstrated similar profiles with regard to safety, morbidity, and mortality.","[{'text': 'albuterol', 'type': 'Chemical', 'start': 23, 'end': 32, 'mesh': 'D000420'}, {'text': 'asthma', 'type': 'Disease', 'start': 60, 'end': 66, 'mesh': 'D001249'}, {'text': 'asthma', 'type': 'Disease', 'start': 235, 'end': 241, 'mesh': 'D001249'}, {'text': 'albuterol', 'type': 'Chemical', 'start': 278, 'end': 287, 'mesh': 'D000420'}, {'text': 'albuterol', 'type': 'Chemical', 'start': 314, 'end': 323, 'mesh': 'D000420'}, {'text': 'asthma', 'type': 'Disease', 'start': 391, 'end': 397, 'mesh': 'D001249'}, {'text': 'cardiac dysrhythmias', 'type': 'Disease', 'start': 478, 'end': 498, 'mesh': 'D001145'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 539, 'end': 550, 'mesh': 'D007008'}]"
+1309,9538487,Hyperosmolar nonketotic coma precipitated by lithium-induced nephrogenic diabetes insipidus.,"A 45-year-old man, with a 10-year history of manic depression treated with lithium, was admitted with hyperosmolar, nonketotic coma. He gave a five-year history of polyuria and polydipsia, during which time urinalysis had been negative for glucose. After recovery from hyperglycaemia, he remained polyuric despite normal blood glucose concentrations; water deprivation testing indicated nephrogenic diabetes insipidus, likely to be lithium-induced. We hypothesize that when this man developed type 2 diabetes, chronic polyuria due to nephrogenic diabetes insipidus was sufficient to precipitate hyperosmolar dehydration.","[{'text': 'Hyperosmolar nonketotic coma', 'type': 'Disease', 'start': 0, 'end': 28, 'mesh': 'D006944'}, {'text': 'lithium', 'type': 'Chemical', 'start': 45, 'end': 52, 'mesh': 'D008094'}, {'text': 'nephrogenic diabetes insipidus', 'type': 'Disease', 'start': 61, 'end': 91, 'mesh': 'D018500'}, {'text': 'manic depression', 'type': 'Disease', 'start': 138, 'end': 154, 'mesh': 'D001714'}, {'text': 'lithium', 'type': 'Chemical', 'start': 168, 'end': 175, 'mesh': 'D008094'}, {'text': 'hyperosmolar, nonketotic coma', 'type': 'Disease', 'start': 195, 'end': 224, 'mesh': 'D006944'}, {'text': 'polyuria', 'type': 'Disease', 'start': 257, 'end': 265, 'mesh': 'D011141'}, {'text': 'polydipsia', 'type': 'Disease', 'start': 270, 'end': 280, 'mesh': 'D059606'}, {'text': 'glucose', 'type': 'Chemical', 'start': 333, 'end': 340, 'mesh': 'D005947'}, {'text': 'hyperglycaemia', 'type': 'Disease', 'start': 362, 'end': 376, 'mesh': '-1'}, {'text': 'polyuric', 'type': 'Disease', 'start': 390, 'end': 398, 'mesh': 'D011141'}, {'text': 'glucose', 'type': 'Chemical', 'start': 420, 'end': 427, 'mesh': 'D005947'}, {'text': 'nephrogenic diabetes insipidus', 'type': 'Disease', 'start': 480, 'end': 510, 'mesh': 'D018500'}, {'text': 'lithium', 'type': 'Chemical', 'start': 525, 'end': 532, 'mesh': 'D008094'}, {'text': 'type 2 diabetes', 'type': 'Disease', 'start': 586, 'end': 601, 'mesh': 'D003924'}, {'text': 'polyuria', 'type': 'Disease', 'start': 611, 'end': 619, 'mesh': 'D011141'}, {'text': 'nephrogenic diabetes insipidus', 'type': 'Disease', 'start': 627, 'end': 657, 'mesh': 'D018500'}, {'text': 'dehydration', 'type': 'Disease', 'start': 701, 'end': 712, 'mesh': 'D003681'}]"
+1310,9570197,Effects of the intracoronary infusion of cocaine on left ventricular systolic and diastolic function in humans.,"BACKGROUND: In dogs, a large amount of intravenous cocaine causes a profound deterioration of left ventricular (LV) systolic function and an increase in LV end-diastolic pressure. This study was done to assess the influence of a high intracoronary cocaine concentration on LV systolic and diastolic function in humans. METHODS AND RESULTS: In 20 patients (14 men and 6 women aged 39 to 72 years) referred for cardiac catheterization for the evaluation of chest pain, we measured heart rate, systemic arterial pressure, LV pressure and its first derivative (dP/dt), and LV volumes and ejection fraction before and during the final 2 to 3 minutes of a 15-minute intracoronary infusion of saline (n=10, control subjects) or cocaine hydrochloride 1 mg/min (n=10). No variable changed with saline. With cocaine, the drug concentration in blood obtained from the coronary sinus was 3.0+/-0.4 (mean+/-SD) mg/L, similar in magnitude to the blood cocaine concentration reported in abusers dying of cocaine intoxication. Cocaine induced no significant change in heart rate, LV dP/dt (positive or negative), or LV end-diastolic volume, but it caused an increase in systolic and mean arterial pressures, LV end-diastolic pressure, and LV end-systolic volume, as well as a decrease in LV ejection fraction. CONCLUSIONS: In humans, the intracoronary infusion of cocaine sufficient in amount to achieve a high drug concentration in coronary sinus blood causes a deterioration of LV systolic and diastolic performance.","[{'text': 'cocaine', 'type': 'Chemical', 'start': 41, 'end': 48, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 163, 'end': 170, 'mesh': 'D003042'}, {'text': 'deterioration of left ventricular (LV) systolic function', 'type': 'Disease', 'start': 189, 'end': 245, 'mesh': 'D018487'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 360, 'end': 367, 'mesh': 'D003042'}, {'text': 'chest pain', 'type': 'Disease', 'start': 567, 'end': 577, 'mesh': 'D002637'}, {'text': 'cocaine hydrochloride', 'type': 'Chemical', 'start': 833, 'end': 854, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 910, 'end': 917, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1050, 'end': 1057, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1101, 'end': 1108, 'mesh': 'D003042'}, {'text': 'Cocaine', 'type': 'Chemical', 'start': 1123, 'end': 1130, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1460, 'end': 1467, 'mesh': 'D003042'}, {'text': 'deterioration of LV systolic and diastolic performance', 'type': 'Disease', 'start': 1559, 'end': 1613, 'mesh': 'D018487'}]"
+1311,9646784,"Heparin-induced thrombocytopenia, paradoxical thromboembolism, and other side effects of heparin therapy.","Although several new anticoagulant drugs are in development, heparin remains the drug of choice for most anticoagulation needs. The clinical effects of heparin are meritorious, but side effects do exist. Important untoward effects of heparin therapy including heparin-induced thrombocytopenia, heparin-associated osteoporosis, eosinophilia, skin reactions, allergic reactions other than thrombocytopenia and alopecia will be discussed in this article.","[{'text': 'Heparin', 'type': 'Chemical', 'start': 0, 'end': 7, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 16, 'end': 32, 'mesh': 'D013921'}, {'text': 'thromboembolism', 'type': 'Disease', 'start': 46, 'end': 61, 'mesh': 'D013923'}, {'text': 'heparin', 'type': 'Chemical', 'start': 89, 'end': 96, 'mesh': 'D006493'}, {'text': 'heparin', 'type': 'Chemical', 'start': 167, 'end': 174, 'mesh': 'D006493'}, {'text': 'heparin', 'type': 'Chemical', 'start': 258, 'end': 265, 'mesh': 'D006493'}, {'text': 'heparin', 'type': 'Chemical', 'start': 340, 'end': 347, 'mesh': 'D006493'}, {'text': 'heparin', 'type': 'Chemical', 'start': 366, 'end': 373, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 382, 'end': 398, 'mesh': 'D013921'}, {'text': 'heparin', 'type': 'Chemical', 'start': 400, 'end': 407, 'mesh': 'D006493'}, {'text': 'osteoporosis', 'type': 'Disease', 'start': 419, 'end': 431, 'mesh': 'D010024'}, {'text': 'eosinophilia', 'type': 'Disease', 'start': 433, 'end': 445, 'mesh': 'D004802'}, {'text': 'skin reactions', 'type': 'Disease', 'start': 447, 'end': 461, 'mesh': 'D012871'}, {'text': 'allergic reactions', 'type': 'Disease', 'start': 463, 'end': 481, 'mesh': 'D004342'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 493, 'end': 509, 'mesh': 'D013921'}, {'text': 'alopecia', 'type': 'Disease', 'start': 514, 'end': 522, 'mesh': 'D000505'}]"
+1312,9725303,Nonopaque crystal deposition causing ureteric obstruction in patients with HIV undergoing indinavir therapy.,"OBJECTIVE: We describe the unique CT features of ureteric calculi in six HIV-infected patients receiving indinavir, the most commonly used HIV protease inhibitor, which is associated with an increased incidence of urolithiasis. CONCLUSION: Ureteric obstruction caused by precipitated indinavir crystals may be difficult to diagnose with unenhanced CT. The calculi are not opaque, and secondary signs of obstruction may be absent or minimal and should be sought carefully. Images may need to be obtained using i.v. contrast material to enable diagnosis of ureteric stones or obstruction in patients with HIV infection who receive indinavir therapy.","[{'text': 'ureteric obstruction', 'type': 'Disease', 'start': 37, 'end': 57, 'mesh': 'D014517'}, {'text': 'indinavir', 'type': 'Chemical', 'start': 90, 'end': 99, 'mesh': 'D019469'}, {'text': 'ureteric calculi', 'type': 'Disease', 'start': 158, 'end': 174, 'mesh': 'D014514'}, {'text': 'HIV-infected', 'type': 'Disease', 'start': 182, 'end': 194, 'mesh': 'D015658'}, {'text': 'indinavir', 'type': 'Chemical', 'start': 214, 'end': 223, 'mesh': 'D019469'}, {'text': 'urolithiasis', 'type': 'Disease', 'start': 323, 'end': 335, 'mesh': 'D052878'}, {'text': 'Ureteric obstruction', 'type': 'Disease', 'start': 349, 'end': 369, 'mesh': 'D014517'}, {'text': 'indinavir', 'type': 'Chemical', 'start': 393, 'end': 402, 'mesh': 'D019469'}, {'text': 'HIV infection', 'type': 'Disease', 'start': 712, 'end': 725, 'mesh': 'D015658'}, {'text': 'indinavir', 'type': 'Chemical', 'start': 738, 'end': 747, 'mesh': 'D019469'}]"
+1313,9759693,Ischemic colitis and sumatriptan use.,"Sumatriptan succinate, a serotonin-1 (5-hydroxytryptamine-1) receptor agonist, is an antimigraine drug that is reported to act by selectively constricting intracranial arteries. Recently, vasopressor responses that are distinct from the cranial circulation have been demonstrated to occur in the systemic, pulmonary, and coronary circulations. Cases have been published of coronary vasospasm, myocardial ischemia, and myocardial infarction occurring after sumatriptan use. We report on the development of 8 serious cases of ischemic colitis in patients with migraine treated with sumatriptan.","[{'text': 'Ischemic colitis', 'type': 'Disease', 'start': 0, 'end': 16, 'mesh': 'D017091'}, {'text': 'sumatriptan', 'type': 'Chemical', 'start': 21, 'end': 32, 'mesh': 'D018170'}, {'text': 'Sumatriptan succinate', 'type': 'Chemical', 'start': 38, 'end': 59, 'mesh': 'D018170'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 63, 'end': 72, 'mesh': 'D012701'}, {'text': '5-hydroxytryptamine', 'type': 'Chemical', 'start': 76, 'end': 95, 'mesh': 'D012701'}, {'text': 'coronary vasospasm', 'type': 'Disease', 'start': 411, 'end': 429, 'mesh': 'D003329'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 431, 'end': 450, 'mesh': 'D017202'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 456, 'end': 477, 'mesh': 'D009203'}, {'text': 'sumatriptan', 'type': 'Chemical', 'start': 494, 'end': 505, 'mesh': 'D018170'}, {'text': 'ischemic colitis', 'type': 'Disease', 'start': 562, 'end': 578, 'mesh': 'D017091'}, {'text': 'migraine', 'type': 'Disease', 'start': 596, 'end': 604, 'mesh': 'D008881'}, {'text': 'sumatriptan', 'type': 'Chemical', 'start': 618, 'end': 629, 'mesh': 'D018170'}]"
+1314,9782254,Pallidotomy with the gamma knife: a positive experience.,"51 patients with medically refractory Parkinson's disease underwent stereotactic posteromedial pallidotomy between August 1993 and February 1997 for treatment of bradykinesia, rigidity, and L-DOPA-induced dyskinesias. In 29 patients, the pallidotomies were performed with the Leksell Gamma Knife and in 22 they were performed with the standard radiofrequency (RF) method. Clinical assessment as well as blinded ratings of Unified Parkinson's Disease Rating Scale (UPDRS) scores were carried out pre- and postoperatively. Mean follow-up time is 20.6 months (range 6-48) and all except 4 patients have been followed more than one year. 85 percent of patients with dyskinesias were relieved of symptoms, regardless of whether the pallidotomies were performed with the Gamma Knife or radiofrequency methods. About 2/3 of the patients in both Gamma Knife and radiofrequency groups showed improvements in bradykinesia and rigidity, although when considered as a group neither the Gamma Knife nor the radiofrequency group showed statistically significant improvements in UPDRS scores. One patient in the Gamma Knife group (3.4%) developed a homonymous hemianopsia 9 months following treatment and 5 patients (27.7%) in the radiofrequency group became transiently confused postoperatively. No other complications were seen. Gamma Knife pallidotomy is as effective as radiofrequency pallidotomy in controlling certain of the symptoms of Parkinson's disease. It may be the only practical technique available in certain patients, such as those who take anticoagulants, have bleeding diatheses or serious systemic medical illnesses. It is a viable option for other patients as well.","[{'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 95, 'end': 114, 'mesh': 'D010300'}, {'text': 'bradykinesia', 'type': 'Disease', 'start': 219, 'end': 231, 'mesh': 'D018476'}, {'text': 'rigidity', 'type': 'Disease', 'start': 233, 'end': 241, 'mesh': 'D009127'}, {'text': 'L-DOPA', 'type': 'Chemical', 'start': 247, 'end': 253, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 262, 'end': 273, 'mesh': 'D004409'}, {'text': ""Parkinson's Disease"", 'type': 'Disease', 'start': 487, 'end': 506, 'mesh': 'D010300'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 719, 'end': 730, 'mesh': 'D004409'}, {'text': 'bradykinesia', 'type': 'Disease', 'start': 956, 'end': 968, 'mesh': 'D018476'}, {'text': 'rigidity', 'type': 'Disease', 'start': 973, 'end': 981, 'mesh': 'D009127'}, {'text': 'homonymous hemianopsia', 'type': 'Disease', 'start': 1191, 'end': 1213, 'mesh': 'D006423'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 1485, 'end': 1504, 'mesh': 'D010300'}, {'text': 'bleeding', 'type': 'Disease', 'start': 1620, 'end': 1628, 'mesh': 'D006470'}]"
+1315,9831002,Neuroleptic malignant syndrome and methylphenidate.,"A 1-year-old female presented with neuroleptic malignant syndrome probably caused by methylphenidate. She had defects in the supratentorial brain including the basal ganglia and the striatum (multicystic encephalomalacia) due to severe perinatal hypoxic-ischemic encephalopathy, which was considered to be a possible predisposing factor causing neuroleptic malignant syndrome. A dopaminergic blockade mechanism generally is accepted as the pathogenesis of this syndrome. However, methylphenidate is a dopamine agonist via the inhibition of uptake of dopamine, and therefore dopaminergic systems in the brainstem (mainly the midbrain) and the spinal cord were unlikely to participate in the onset of this syndrome. A relative gamma-aminobutyric acid-ergic deficiency might occur because diazepam, a gamma-aminobutyric acid-mimetic agent, was strikingly effective. This is the first reported patient with neuroleptic malignant syndrome probably caused by methylphenidate.","[{'text': 'Neuroleptic malignant syndrome', 'type': 'Disease', 'start': 0, 'end': 30, 'mesh': 'D009459'}, {'text': 'methylphenidate', 'type': 'Chemical', 'start': 35, 'end': 50, 'mesh': 'D008774'}, {'text': 'neuroleptic malignant syndrome', 'type': 'Disease', 'start': 87, 'end': 117, 'mesh': 'D009459'}, {'text': 'methylphenidate', 'type': 'Chemical', 'start': 137, 'end': 152, 'mesh': 'D008774'}, {'text': 'multicystic encephalomalacia', 'type': 'Disease', 'start': 244, 'end': 272, 'mesh': 'D004678'}, {'text': 'hypoxic-ischemic encephalopathy', 'type': 'Disease', 'start': 298, 'end': 329, 'mesh': 'D020925'}, {'text': 'neuroleptic malignant syndrome', 'type': 'Disease', 'start': 397, 'end': 427, 'mesh': 'D009459'}, {'text': 'methylphenidate', 'type': 'Chemical', 'start': 532, 'end': 547, 'mesh': 'D008774'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 553, 'end': 561, 'mesh': 'D004298'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 602, 'end': 610, 'mesh': 'D004298'}, {'text': 'gamma-aminobutyric acid', 'type': 'Chemical', 'start': 777, 'end': 800, 'mesh': 'D005680'}, {'text': 'diazepam', 'type': 'Chemical', 'start': 838, 'end': 846, 'mesh': 'D003975'}, {'text': 'gamma-aminobutyric acid', 'type': 'Chemical', 'start': 850, 'end': 873, 'mesh': 'D005680'}, {'text': 'neuroleptic malignant syndrome', 'type': 'Disease', 'start': 955, 'end': 985, 'mesh': 'D009459'}, {'text': 'methylphenidate', 'type': 'Chemical', 'start': 1005, 'end': 1020, 'mesh': 'D008774'}]"
+1316,9869655,Differential effects of 17alpha-ethinylestradiol on the neutral and acidic pathways of bile salt synthesis in the rat.,"Effects of 17alpha-ethinylestradiol (EE) on the neutral and acidic biosynthetic pathways of bile salt (BS) synthesis were evaluated in rats with an intact enterohepatic circulation and in rats with long-term bile diversion to induce BS synthesis. For this purpose, bile salt pool composition, synthesis of individual BS in vivo, hepatic activities, and expression levels of cholesterol 7alpha-hydroxylase (CYP7A), and sterol 27-hydroxylase (CYP27), as well as of other enzymes involved in BS synthesis, were analyzed in rats treated with EE (5 mg/kg, 3 days) or its vehicle. BS pool size was decreased by 27% but total BS synthesis was not affected by EE in intact rats. Synthesis of cholate was reduced by 68% in EE-treated rats, while that of chenodeoxycholate was increased by 60%. The recently identified Delta22-isomer of beta-muricholate contributed for 5.4% and 18.3 % (P < 0.01) to the pool in control and EE-treated rats, respectively, but could not be detected in bile after exhaustion of the pool. A clear reduction of BS synthesis was found in bile-diverted rats treated with EE, yet biliary BS composition was only minimally affected. Activity of CYP7A was decreased by EE in both intact and bile-diverted rats, whereas the activity of the CYP27 was not affected. Hepatic mRNA levels of CYP7A were significantly reduced by EE in bile-diverted rats only; CYP27 mRNA levels were not affected by EE. In addition, mRNA levels of sterol 12alpha-hydroxylase and lithocholate 6beta-hydroxylase were increased by bile diversion and suppressed by EE. This study shows that 17alpha-ethinylestradiol (EE)-induced intrahepatic cholestasis in rats is associated with selective inhibition of the neutral pathway of bile salt (BS) synthesis. Simultaneous impairment of other enzymes in the BS biosynthetic pathways may contribute to overall effects of EE on BS synthesis.","[{'text': '17alpha-ethinylestradiol', 'type': 'Chemical', 'start': 24, 'end': 48, 'mesh': 'D004997'}, {'text': 'bile salt', 'type': 'Chemical', 'start': 87, 'end': 96, 'mesh': 'D001647'}, {'text': '17alpha-ethinylestradiol', 'type': 'Chemical', 'start': 130, 'end': 154, 'mesh': 'D004997'}, {'text': 'EE', 'type': 'Chemical', 'start': 156, 'end': 158, 'mesh': 'D004997'}, {'text': 'bile salt', 'type': 'Chemical', 'start': 211, 'end': 220, 'mesh': 'D001647'}, {'text': 'BS', 'type': 'Chemical', 'start': 222, 'end': 224, 'mesh': 'D001647'}, {'text': 'BS', 'type': 'Chemical', 'start': 352, 'end': 354, 'mesh': 'D001647'}, {'text': 'bile salt', 'type': 'Chemical', 'start': 384, 'end': 393, 'mesh': 'D001647'}, {'text': 'BS', 'type': 'Chemical', 'start': 436, 'end': 438, 'mesh': 'D001647'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 493, 'end': 504, 'mesh': 'D002784'}, {'text': 'sterol', 'type': 'Chemical', 'start': 537, 'end': 543, 'mesh': 'D013261'}, {'text': 'BS', 'type': 'Chemical', 'start': 608, 'end': 610, 'mesh': 'D001647'}, {'text': 'EE', 'type': 'Chemical', 'start': 657, 'end': 659, 'mesh': 'D004997'}, {'text': 'BS', 'type': 'Chemical', 'start': 694, 'end': 696, 'mesh': 'D001647'}, {'text': 'BS', 'type': 'Chemical', 'start': 738, 'end': 740, 'mesh': 'D001647'}, {'text': 'EE', 'type': 'Chemical', 'start': 771, 'end': 773, 'mesh': 'D004997'}, {'text': 'cholate', 'type': 'Chemical', 'start': 803, 'end': 810, 'mesh': 'D020355'}, {'text': 'EE', 'type': 'Chemical', 'start': 833, 'end': 835, 'mesh': 'D004997'}, {'text': 'chenodeoxycholate', 'type': 'Chemical', 'start': 864, 'end': 881, 'mesh': 'D002635'}, {'text': 'EE', 'type': 'Chemical', 'start': 1033, 'end': 1035, 'mesh': 'D004997'}, {'text': 'BS', 'type': 'Chemical', 'start': 1149, 'end': 1151, 'mesh': 'D001647'}, {'text': 'EE', 'type': 'Chemical', 'start': 1207, 'end': 1209, 'mesh': 'D004997'}, {'text': 'BS', 'type': 'Chemical', 'start': 1223, 'end': 1225, 'mesh': 'D001647'}, {'text': 'EE', 'type': 'Chemical', 'start': 1302, 'end': 1304, 'mesh': 'D004997'}, {'text': 'EE', 'type': 'Chemical', 'start': 1455, 'end': 1457, 'mesh': 'D004997'}, {'text': 'EE', 'type': 'Chemical', 'start': 1525, 'end': 1527, 'mesh': 'D004997'}, {'text': 'sterol', 'type': 'Chemical', 'start': 1557, 'end': 1563, 'mesh': 'D013261'}, {'text': 'EE', 'type': 'Chemical', 'start': 1670, 'end': 1672, 'mesh': 'D004997'}, {'text': '17alpha-ethinylestradiol', 'type': 'Chemical', 'start': 1696, 'end': 1720, 'mesh': 'D004997'}, {'text': 'EE', 'type': 'Chemical', 'start': 1722, 'end': 1724, 'mesh': 'D004997'}, {'text': 'intrahepatic cholestasis', 'type': 'Disease', 'start': 1734, 'end': 1758, 'mesh': 'D002780'}, {'text': 'bile salt', 'type': 'Chemical', 'start': 1833, 'end': 1842, 'mesh': 'D001647'}, {'text': 'BS', 'type': 'Chemical', 'start': 1844, 'end': 1846, 'mesh': 'D001647'}, {'text': 'BS', 'type': 'Chemical', 'start': 1907, 'end': 1909, 'mesh': 'D001647'}, {'text': 'EE', 'type': 'Chemical', 'start': 1969, 'end': 1971, 'mesh': 'D004997'}, {'text': 'BS', 'type': 'Chemical', 'start': 1975, 'end': 1977, 'mesh': 'D001647'}]"
+1317,9881641,Glibenclamide-sensitive hypotension produced by helodermin assessed in the rat.,"The effects of helodermin, a basic 35-amino acid peptide isolated from the venom of a lizard salivary gland, on arterial blood pressure and heart rate were examined in the rat, focusing on the possibility that activation of ATP sensitive K+ (K(ATP)) channels is involved in the responses. The results were also compared with those of vasoactive intestinal polypeptide (VIP). Helodermin produced hypotension in a dose-dependent manner with approximately similar potency and duration to VIP. Hypotension induced by both peptides was significantly attenuated by glibenclamide, which abolished a levcromakalim-produced decrease in arterial blood pressure. Oxyhemoglobin did not affect helodermin-induced hypotension, whereas it shortened the duration of acetylcholine (ACh)-produced hypotension. These findings suggest that helodermin-produced hypotension is partly attributable to the activation of glibenclamide-sensitive K+ channels (K(ATP) channels), which presumably exist on arterial smooth muscle cells. EDRF (endothelium-derived relaxing factor)/nitric oxide does not seem to play an important role in the peptide-produced hypotension.","[{'text': 'Glibenclamide', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'D005905'}, {'text': 'hypotension', 'type': 'Disease', 'start': 24, 'end': 35, 'mesh': 'D007022'}, {'text': 'helodermin', 'type': 'Chemical', 'start': 48, 'end': 58, 'mesh': 'C040442'}, {'text': 'helodermin', 'type': 'Chemical', 'start': 95, 'end': 105, 'mesh': 'C040442'}, {'text': 'amino acid', 'type': 'Chemical', 'start': 118, 'end': 128, 'mesh': 'D000596'}, {'text': 'ATP', 'type': 'Chemical', 'start': 304, 'end': 307, 'mesh': 'D000255'}, {'text': 'K', 'type': 'Chemical', 'start': 318, 'end': 319, 'mesh': 'D011188'}, {'text': 'K', 'type': 'Chemical', 'start': 322, 'end': 323, 'mesh': 'D011188'}, {'text': 'ATP', 'type': 'Chemical', 'start': 324, 'end': 327, 'mesh': 'D000255'}, {'text': 'Helodermin', 'type': 'Chemical', 'start': 455, 'end': 465, 'mesh': 'C040442'}, {'text': 'hypotension', 'type': 'Disease', 'start': 475, 'end': 486, 'mesh': 'D007022'}, {'text': 'Hypotension', 'type': 'Disease', 'start': 570, 'end': 581, 'mesh': 'D007022'}, {'text': 'glibenclamide', 'type': 'Chemical', 'start': 639, 'end': 652, 'mesh': 'D005905'}, {'text': 'levcromakalim', 'type': 'Chemical', 'start': 672, 'end': 685, 'mesh': 'D019806'}, {'text': 'helodermin', 'type': 'Chemical', 'start': 761, 'end': 771, 'mesh': 'C040442'}, {'text': 'hypotension', 'type': 'Disease', 'start': 780, 'end': 791, 'mesh': 'D007022'}, {'text': 'acetylcholine', 'type': 'Chemical', 'start': 830, 'end': 843, 'mesh': 'D000109'}, {'text': 'ACh', 'type': 'Chemical', 'start': 845, 'end': 848, 'mesh': 'D000109'}, {'text': 'hypotension', 'type': 'Disease', 'start': 859, 'end': 870, 'mesh': 'D007022'}, {'text': 'helodermin', 'type': 'Chemical', 'start': 900, 'end': 910, 'mesh': 'C040442'}, {'text': 'hypotension', 'type': 'Disease', 'start': 920, 'end': 931, 'mesh': 'D007022'}, {'text': 'glibenclamide', 'type': 'Chemical', 'start': 976, 'end': 989, 'mesh': 'D005905'}, {'text': 'K', 'type': 'Chemical', 'start': 1000, 'end': 1001, 'mesh': 'D011188'}, {'text': 'K', 'type': 'Chemical', 'start': 1013, 'end': 1014, 'mesh': 'D011188'}, {'text': 'ATP', 'type': 'Chemical', 'start': 1015, 'end': 1018, 'mesh': 'D000255'}, {'text': 'nitric oxide', 'type': 'Chemical', 'start': 1130, 'end': 1142, 'mesh': 'D009569'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1207, 'end': 1218, 'mesh': 'D007022'}]"
+1318,9889429,Long-term efficacy and adverse event of nifedipine sustained-release tablets for cyclosporin A-induced hypertension in patients with psoriasis.,"Thirteen psoriatic patients with hypertension during the course of cyclosporin A therapy were treated for 25 months with a calcium channel blocker, sustained-release nifedipine, to study the clinical antihypertensive effects and adverse events during treatment with both drugs. Seven of the 13 patients had exhibited a subclinical hypertensive state before cyclosporin A therapy. Both systolic and diastolic blood pressures of these 13 patients were decreased significantly after 4 weeks of nifedipine therapy, and blood pressure was maintained within the normal range thereafter for 25 months. The adverse events during combined therapy with cyclosporin A and nifedipine included an increase in blood urea nitrogen levels in 9 of the 13 patients and development of gingival hyperplasia in 2 of the 13 patients. Our findings indicate that sustained-release nifedipine is useful for hypertensive psoriatic patients under long-term treatment with cyclosporin A, but that these patients should be monitored for gingival hyperplasia.","[{'text': 'nifedipine', 'type': 'Chemical', 'start': 40, 'end': 50, 'mesh': 'D009543'}, {'text': 'cyclosporin A', 'type': 'Chemical', 'start': 81, 'end': 94, 'mesh': 'D016572'}, {'text': 'hypertension', 'type': 'Disease', 'start': 103, 'end': 115, 'mesh': 'D006973'}, {'text': 'psoriasis', 'type': 'Disease', 'start': 133, 'end': 142, 'mesh': 'D011565'}, {'text': 'psoriatic', 'type': 'Disease', 'start': 153, 'end': 162, 'mesh': 'D011565'}, {'text': 'hypertension', 'type': 'Disease', 'start': 177, 'end': 189, 'mesh': 'D006973'}, {'text': 'cyclosporin A', 'type': 'Chemical', 'start': 211, 'end': 224, 'mesh': 'D016572'}, {'text': 'calcium', 'type': 'Chemical', 'start': 267, 'end': 274, 'mesh': 'D002118'}, {'text': 'nifedipine', 'type': 'Chemical', 'start': 310, 'end': 320, 'mesh': 'D009543'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 475, 'end': 487, 'mesh': 'D006973'}, {'text': 'cyclosporin A', 'type': 'Chemical', 'start': 501, 'end': 514, 'mesh': 'D016572'}, {'text': 'nifedipine', 'type': 'Chemical', 'start': 635, 'end': 645, 'mesh': 'D009543'}, {'text': 'cyclosporin A', 'type': 'Chemical', 'start': 787, 'end': 800, 'mesh': 'D016572'}, {'text': 'nifedipine', 'type': 'Chemical', 'start': 805, 'end': 815, 'mesh': 'D009543'}, {'text': 'blood urea nitrogen', 'type': 'Chemical', 'start': 840, 'end': 859, 'mesh': 'D001806'}, {'text': 'gingival hyperplasia', 'type': 'Disease', 'start': 910, 'end': 930, 'mesh': 'D005885'}, {'text': 'nifedipine', 'type': 'Chemical', 'start': 1001, 'end': 1011, 'mesh': 'D009543'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 1026, 'end': 1038, 'mesh': 'D006973'}, {'text': 'psoriatic', 'type': 'Disease', 'start': 1039, 'end': 1048, 'mesh': 'D011565'}, {'text': 'cyclosporin A', 'type': 'Chemical', 'start': 1089, 'end': 1102, 'mesh': 'D016572'}, {'text': 'gingival hyperplasia', 'type': 'Disease', 'start': 1152, 'end': 1172, 'mesh': 'D005885'}]"
+1319,10087562,Torsade de pointes ventricular tachycardia during low dose intermittent dobutamine treatment in a patient with dilated cardiomyopathy and congestive heart failure.,"The authors describe the case of a 56-year-old woman with chronic, severe heart failure secondary to dilated cardiomyopathy and absence of significant ventricular arrhythmias who developed QT prolongation and torsade de pointes ventricular tachycardia during one cycle of intermittent low dose (2.5 mcg/kg per min) dobutamine. This report of torsade de pointes ventricular tachycardia during intermittent dobutamine supports the hypothesis that unpredictable fatal arrhythmias may occur even with low doses and in patients with no history of significant rhythm disturbances. The mechanisms of proarrhythmic effects of Dubutamine are discussed.","[{'text': 'Torsade de pointes', 'type': 'Disease', 'start': 0, 'end': 18, 'mesh': 'D016171'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 19, 'end': 42, 'mesh': 'D017180'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 72, 'end': 82, 'mesh': 'D004280'}, {'text': 'dilated cardiomyopathy', 'type': 'Disease', 'start': 111, 'end': 133, 'mesh': 'D002311'}, {'text': 'congestive heart failure', 'type': 'Disease', 'start': 138, 'end': 162, 'mesh': 'D006333'}, {'text': 'heart failure', 'type': 'Disease', 'start': 238, 'end': 251, 'mesh': 'D006333'}, {'text': 'dilated cardiomyopathy', 'type': 'Disease', 'start': 265, 'end': 287, 'mesh': 'D002311'}, {'text': 'ventricular arrhythmias', 'type': 'Disease', 'start': 315, 'end': 338, 'mesh': 'D001145'}, {'text': 'QT prolongation', 'type': 'Disease', 'start': 353, 'end': 368, 'mesh': 'D008133'}, {'text': 'torsade de pointes', 'type': 'Disease', 'start': 373, 'end': 391, 'mesh': 'D016171'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 392, 'end': 415, 'mesh': 'D017180'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 479, 'end': 489, 'mesh': 'D004280'}, {'text': 'torsade de pointes', 'type': 'Disease', 'start': 506, 'end': 524, 'mesh': 'D016171'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 525, 'end': 548, 'mesh': 'D017180'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 569, 'end': 579, 'mesh': 'D004280'}, {'text': 'arrhythmias', 'type': 'Disease', 'start': 629, 'end': 640, 'mesh': 'D001145'}, {'text': 'Dubutamine', 'type': 'Chemical', 'start': 782, 'end': 792, 'mesh': 'D004280'}]"
+1320,10219427,Positive skin tests in late reactions to radiographic contrast media.,"In the last few years delayed reactions several hours after the injection of radiographic and contrast materials (PRC) have been described with increasing frequency. The authors report two observations on patients with delayed reactions in whom intradermoreactions (IDR) and patch tests to a series of ionic and non ionic PRC were studied. After angiography by the venous route in patient n degree 1 a biphasic reaction with an immediate reaction (dyspnea, loss of consciousness) and delayed macro-papular rash appeared, whilst patient n degree 2 developed a generalised sensation of heat, persistent pain at the site of injection immediately and a generalised macro-papular reaction after 24 hours. The skin tests revealed positive delayed reactions of 24 hours and 48 hours by IDR and patch tests to only some PRC with common chains in their structures. The positive skin tests are in favour of immunological reactions and may help in diagnosis of allergy in the patients.","[{'text': 'contrast media', 'type': 'Chemical', 'start': 54, 'end': 68, 'mesh': 'D003287'}, {'text': 'contrast materials', 'type': 'Chemical', 'start': 164, 'end': 182, 'mesh': 'D003287'}, {'text': 'PRC', 'type': 'Chemical', 'start': 184, 'end': 187, 'mesh': 'D003287'}, {'text': 'PRC', 'type': 'Chemical', 'start': 392, 'end': 395, 'mesh': 'D003287'}, {'text': 'dyspnea', 'type': 'Disease', 'start': 518, 'end': 525, 'mesh': 'D004417'}, {'text': 'loss of consciousness', 'type': 'Disease', 'start': 527, 'end': 548, 'mesh': 'D014474'}, {'text': 'macro-papular rash', 'type': 'Disease', 'start': 562, 'end': 580, 'mesh': 'D003875'}, {'text': 'pain', 'type': 'Disease', 'start': 671, 'end': 675, 'mesh': 'D010146'}, {'text': 'PRC', 'type': 'Chemical', 'start': 882, 'end': 885, 'mesh': 'D003287'}, {'text': 'allergy', 'type': 'Disease', 'start': 1020, 'end': 1027, 'mesh': 'D004342'}]"
+1321,10327032,Risk of transient hyperammonemic encephalopathy in cancer patients who received continuous infusion of 5-fluorouracil with the complication of dehydration and infection.,"From 1986 to 1998, 29 cancer patients who had 32 episodes of transient hyperammonemic encephalopathy related to continuous infusion of 5-fluorouracil (5-FU) were identified. None of the patients had decompensated liver disease. Onset of hyperammonemic encephalopathy varied from 0.5 to 5 days (mean: 2.6 +/- 1.3 days) after the initiation of chemotherapy. Plasma ammonium level ranged from 248 to 2387 microg% (mean: 626 +/- 431 microg%). Among the 32 episodes, 26 (81%) had various degrees of azotemia, 18 (56%) occurred during bacterial infections and 14 (44%) without infection occurred during periods of dehydration. Higher plasma ammonium levels and more rapid onset of hyperammonemia were seen in 18 patients with bacterial infections (p=0.003 and 0.0006, respectively) and in nine patients receiving high daily doses (2600 or 1800 mg/m2) of 5-FU (p=0.0001 and < 0.0001, respectively). In 25 out of 32 episodes (78%), plasma ammonium levels and mental status returned to normal within 2 days after adequate management. In conclusion, hyperammonemic encephalopathy can occur in patients receiving continuous infusion of 5-FU. Azotemia, body fluid insufficiency and bacterial infections were frequently found in these patients. It is therefore important to recognize this condition in patients receiving continuous infusion of 5-FU.","[{'text': 'cancer', 'type': 'Disease', 'start': 51, 'end': 57, 'mesh': 'D009369'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 103, 'end': 117, 'mesh': 'D005472'}, {'text': 'dehydration', 'type': 'Disease', 'start': 143, 'end': 154, 'mesh': 'D003681'}, {'text': 'infection', 'type': 'Disease', 'start': 159, 'end': 168, 'mesh': 'D007239'}, {'text': 'cancer', 'type': 'Disease', 'start': 192, 'end': 198, 'mesh': 'D009369'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 305, 'end': 319, 'mesh': 'D005472'}, {'text': '5-FU', 'type': 'Chemical', 'start': 321, 'end': 325, 'mesh': 'D005472'}, {'text': 'liver disease', 'type': 'Disease', 'start': 383, 'end': 396, 'mesh': 'D008107'}, {'text': 'ammonium', 'type': 'Chemical', 'start': 533, 'end': 541, 'mesh': 'D000644'}, {'text': 'azotemia', 'type': 'Disease', 'start': 664, 'end': 672, 'mesh': 'D053099'}, {'text': 'bacterial infections', 'type': 'Disease', 'start': 699, 'end': 719, 'mesh': 'D001424'}, {'text': 'infection', 'type': 'Disease', 'start': 741, 'end': 750, 'mesh': 'D007239'}, {'text': 'dehydration', 'type': 'Disease', 'start': 778, 'end': 789, 'mesh': 'D003681'}, {'text': 'ammonium', 'type': 'Chemical', 'start': 805, 'end': 813, 'mesh': 'D000644'}, {'text': 'hyperammonemia', 'type': 'Disease', 'start': 845, 'end': 859, 'mesh': 'D022124'}, {'text': 'bacterial infections', 'type': 'Disease', 'start': 890, 'end': 910, 'mesh': 'D001424'}, {'text': '5-FU', 'type': 'Chemical', 'start': 1018, 'end': 1022, 'mesh': 'D005472'}, {'text': 'ammonium', 'type': 'Chemical', 'start': 1101, 'end': 1109, 'mesh': 'D000644'}, {'text': '5-FU', 'type': 'Chemical', 'start': 1295, 'end': 1299, 'mesh': 'D005472'}, {'text': 'Azotemia', 'type': 'Disease', 'start': 1301, 'end': 1309, 'mesh': 'D053099'}, {'text': 'bacterial infections', 'type': 'Disease', 'start': 1340, 'end': 1360, 'mesh': 'D001424'}, {'text': '5-FU', 'type': 'Chemical', 'start': 1501, 'end': 1505, 'mesh': 'D005472'}]"
+1322,10390729,The effects of quinine and 4-aminopyridine on conditioned place preference and changes in motor activity induced by morphine in rats.,"1. The effects of two unselective potassium (K(+)-) channel blockers, quinine (12.5, 25 and 50 mg/kg) and 4-aminopyridine (1 and 2 mg/kg), on conditioned place preference and biphasic changes in motor activity induced by morphine (10 mg/kg) were tested in Wistar rats. Quinine is known to block voltage-, calcium- and ATP-sensitive K(+)-channels while 4-aminopyridine is known to block voltage-sensitive K(+)-channels. 2. In the counterbalanced method, quinine attenuated morphine-induced place preference, whereas 4-aminopyridine was ineffective. In the motor activity test measured with an Animex-activity meter neither of the K(+)-channel blockers affected morphine-induced hypoactivity, but both K(+)-channel blockers prevented morphine-induced secondary hyperactivity. 3. These results suggest the involvement of quinine-sensitive but not 4-aminopyridine-sensitive K(+)-channels in morphine reward. It is also suggested that the blockade of K(+)-channels sensitive to these blockers is not sufficient to prevent morphine-induced hypoactivity whereas morphine-induced hyperactivity seems to be connected to both quinine- and 4-aminopyridine-sensitive K(+)-channels.","[{'text': 'quinine', 'type': 'Chemical', 'start': 15, 'end': 22, 'mesh': 'D011803'}, {'text': '4-aminopyridine', 'type': 'Chemical', 'start': 27, 'end': 42, 'mesh': 'D015761'}, {'text': 'morphine', 'type': 'Chemical', 'start': 116, 'end': 124, 'mesh': 'D009020'}, {'text': 'potassium', 'type': 'Chemical', 'start': 168, 'end': 177, 'mesh': 'D011188'}, {'text': 'K', 'type': 'Chemical', 'start': 179, 'end': 180, 'mesh': 'D011188'}, {'text': 'quinine', 'type': 'Chemical', 'start': 204, 'end': 211, 'mesh': 'D011803'}, {'text': '4-aminopyridine', 'type': 'Chemical', 'start': 240, 'end': 255, 'mesh': 'D015761'}, {'text': 'morphine', 'type': 'Chemical', 'start': 355, 'end': 363, 'mesh': 'D009020'}, {'text': 'Quinine', 'type': 'Chemical', 'start': 403, 'end': 410, 'mesh': 'D011803'}, {'text': 'calcium', 'type': 'Chemical', 'start': 439, 'end': 446, 'mesh': 'D002118'}, {'text': 'ATP', 'type': 'Chemical', 'start': 452, 'end': 455, 'mesh': 'D000255'}, {'text': 'K', 'type': 'Chemical', 'start': 466, 'end': 467, 'mesh': 'D011188'}, {'text': '4-aminopyridine', 'type': 'Chemical', 'start': 486, 'end': 501, 'mesh': 'D015761'}, {'text': 'K', 'type': 'Chemical', 'start': 538, 'end': 539, 'mesh': 'D011188'}, {'text': 'quinine', 'type': 'Chemical', 'start': 587, 'end': 594, 'mesh': 'D011803'}, {'text': 'morphine', 'type': 'Chemical', 'start': 606, 'end': 614, 'mesh': 'D009020'}, {'text': '4-aminopyridine', 'type': 'Chemical', 'start': 649, 'end': 664, 'mesh': 'D015761'}, {'text': 'K', 'type': 'Chemical', 'start': 763, 'end': 764, 'mesh': 'D011188'}, {'text': 'morphine', 'type': 'Chemical', 'start': 794, 'end': 802, 'mesh': 'D009020'}, {'text': 'hypoactivity', 'type': 'Disease', 'start': 811, 'end': 823, 'mesh': 'D009069'}, {'text': 'K', 'type': 'Chemical', 'start': 834, 'end': 835, 'mesh': 'D011188'}, {'text': 'morphine', 'type': 'Chemical', 'start': 866, 'end': 874, 'mesh': 'D009020'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 893, 'end': 906, 'mesh': 'D006948'}, {'text': 'quinine', 'type': 'Chemical', 'start': 952, 'end': 959, 'mesh': 'D011803'}, {'text': '4-aminopyridine', 'type': 'Chemical', 'start': 978, 'end': 993, 'mesh': 'D015761'}, {'text': 'K', 'type': 'Chemical', 'start': 1004, 'end': 1005, 'mesh': 'D011188'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1021, 'end': 1029, 'mesh': 'D009020'}, {'text': 'K', 'type': 'Chemical', 'start': 1080, 'end': 1081, 'mesh': 'D011188'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1151, 'end': 1159, 'mesh': 'D009020'}, {'text': 'hypoactivity', 'type': 'Disease', 'start': 1168, 'end': 1180, 'mesh': 'D009069'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1189, 'end': 1197, 'mesh': 'D009020'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 1206, 'end': 1219, 'mesh': 'D006948'}, {'text': 'quinine', 'type': 'Chemical', 'start': 1250, 'end': 1257, 'mesh': 'D011803'}, {'text': '4-aminopyridine', 'type': 'Chemical', 'start': 1263, 'end': 1278, 'mesh': 'D015761'}, {'text': 'K', 'type': 'Chemical', 'start': 1289, 'end': 1290, 'mesh': 'D011188'}]"
+1323,10401555,Nociceptin/orphanin FQ and nocistatin on learning and memory impairment induced by scopolamine in mice.,"1. Nociceptin, also known as orphanin FQ, is an endogenous ligand for the orphan opioid receptor-like receptor 1 (ORL1) and involves in various functions in the central nervous system (CNS). On the other hand, nocistatin is recently isolated from the same precursor as nociceptin and blocks nociceptin-induced allodynia and hyperalgesia. 2. Although ORL1 receptors which display a high degree of sequence homology with classical opioid receptors are abundant in the hippocampus, little is known regarding their role in learning and memory. 3. The present study was designed to investigate whether nociceptin/orphanin FQ and nocistatin could modulate impairment of learning and memory induced by scopolamine, a muscarinic cholinergic receptor antagonist, using spontaneous alternation of Y-maze and step-down type passive avoidance tasks in mice. 4. While nocistatin (0.5-5.0 nmol mouse-1, i.c.v.) administered 30 min before spontaneous alternation performance or the training session of the passive avoidance task, had no effect on spontaneous alternation or passive avoidance behaviours, a lower per cent alternation and shorter median step-down latency in the retention test were obtained in nociceptin (1.5 and/or 5.0 nmol mouse-1, i.c.v.)-treated normal mice. 5. Administration of nocistatin (1.5 and/or 5.0 nmol mouse-1, i.c.v.) 30 min before spontaneous alternation performance or the training session of the passive avoidance task, attenuated the scopolamine-induced impairment of spontaneous alternation and passive avoidance behaviours. 6. These results indicated that nocistatin, a new biologically active peptide, ameliorates impairments of spontaneous alternation and passive avoidance induced by scopolamine, and suggested that these peptides play opposite roles in learning and memory.","[{'text': 'Nociceptin', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'C096012'}, {'text': 'orphanin FQ', 'type': 'Chemical', 'start': 11, 'end': 22, 'mesh': 'C096012'}, {'text': 'nocistatin', 'type': 'Chemical', 'start': 27, 'end': 37, 'mesh': 'C111148'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 83, 'end': 94, 'mesh': 'D012601'}, {'text': 'Nociceptin', 'type': 'Chemical', 'start': 107, 'end': 117, 'mesh': 'C096012'}, {'text': 'orphanin FQ', 'type': 'Chemical', 'start': 133, 'end': 144, 'mesh': 'C096012'}, {'text': 'nocistatin', 'type': 'Chemical', 'start': 314, 'end': 324, 'mesh': 'C111148'}, {'text': 'nociceptin', 'type': 'Chemical', 'start': 373, 'end': 383, 'mesh': 'C096012'}, {'text': 'nociceptin', 'type': 'Chemical', 'start': 395, 'end': 405, 'mesh': 'C096012'}, {'text': 'allodynia', 'type': 'Disease', 'start': 414, 'end': 423, 'mesh': 'D006930'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 428, 'end': 440, 'mesh': 'D006930'}, {'text': 'nociceptin', 'type': 'Chemical', 'start': 701, 'end': 711, 'mesh': 'C096012'}, {'text': 'orphanin FQ', 'type': 'Chemical', 'start': 712, 'end': 723, 'mesh': 'C096012'}, {'text': 'nocistatin', 'type': 'Chemical', 'start': 728, 'end': 738, 'mesh': 'C111148'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 799, 'end': 810, 'mesh': 'D012601'}, {'text': 'nocistatin', 'type': 'Chemical', 'start': 959, 'end': 969, 'mesh': 'C111148'}, {'text': 'nociceptin', 'type': 'Chemical', 'start': 1298, 'end': 1308, 'mesh': 'C096012'}, {'text': 'nocistatin', 'type': 'Chemical', 'start': 1389, 'end': 1399, 'mesh': 'C111148'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 1558, 'end': 1569, 'mesh': 'D012601'}, {'text': 'nocistatin', 'type': 'Chemical', 'start': 1682, 'end': 1692, 'mesh': 'C111148'}, {'text': 'scopolamine', 'type': 'Chemical', 'start': 1813, 'end': 1824, 'mesh': 'D012601'}]"
+1324,10427794,Meloxicam-induced liver toxicity.,"We report the case of a female patient with rheumatoid arthritis who developed acute cytolytic hepatitis due to meloxicam. Recently introduced in Belgium, meloxicam is the first nonsteroidal antiinflammatory drug with selective action on the inducible form of cyclooxygenase 2. The acute cytolytic hepatitis occurred rapidly after meloxicam administration and was associated with the development of antinuclear antibodies suggesting a hypersensitivity mechanism. This first case of meloxicam related liver toxicity demonstrates the potential of this drug to induce hepatic damage.","[{'text': 'Meloxicam', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'C065757'}, {'text': 'liver toxicity', 'type': 'Disease', 'start': 18, 'end': 32, 'mesh': 'D056486'}, {'text': 'rheumatoid arthritis', 'type': 'Disease', 'start': 78, 'end': 98, 'mesh': 'D001172'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 129, 'end': 138, 'mesh': 'D056486'}, {'text': 'meloxicam', 'type': 'Chemical', 'start': 146, 'end': 155, 'mesh': 'C065757'}, {'text': 'meloxicam', 'type': 'Chemical', 'start': 189, 'end': 198, 'mesh': 'C065757'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 332, 'end': 341, 'mesh': 'D056486'}, {'text': 'meloxicam', 'type': 'Chemical', 'start': 365, 'end': 374, 'mesh': 'C065757'}, {'text': 'hypersensitivity', 'type': 'Disease', 'start': 469, 'end': 485, 'mesh': 'D004342'}, {'text': 'meloxicam', 'type': 'Chemical', 'start': 516, 'end': 525, 'mesh': 'C065757'}, {'text': 'liver toxicity', 'type': 'Disease', 'start': 534, 'end': 548, 'mesh': 'D056486'}, {'text': 'hepatic damage', 'type': 'Disease', 'start': 599, 'end': 613, 'mesh': 'D056486'}]"
+1325,10462057,Induction of apoptosis by remoxipride metabolites in HL60 and CD34+/CD19- human bone marrow progenitor cells: potential relevance to remoxipride-induced aplastic anemia.,"The antipsychotic agent, remoxipride [(S)-(-)-3-bromo-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2,6-dimethoxybenz amide] has been associated with acquired aplastic anemia. We have examined the ability of remoxipride, three pyrrolidine ring metabolites and five aromatic ring metabolites of the parent compound to induce apoptosis in HL60 cells and human bone marrow progenitor (HBMP) cells. Cells were treated for 0-24 h with each compound (0-200 microM). Apoptosis was assessed by fluorescence microscopy in Hoechst 33342- and propidium iodide stained cell samples. Results were confirmed by determination of internucleosomal DNA fragmentation using gel electrophoresis for HL60 cell samples and terminal deoxynucleotidyl transferase assay in HBMP cells. The catechol and hydroquinone metabolites, NCQ436 and NCQ344, induced apoptosis in HL60 and HBMP cells in a time- and concentration dependent manner, while the phenols, NCR181, FLA873, and FLA797, and the derivatives formed by oxidation of the pyrrolidine ring, FLA838, NCM001, and NCL118, had no effect. No necrosis was observed in cells treated with NCQ436 but NCQ344 had a biphasic effect in both cell types, inducing apoptosis at lower concentrations and necrosis at higher concentrations. These data show that the catechol and hydroquinone metabolites of remoxipride have direct toxic effects in HL60 and HBMP cells, leading to apoptosis, while the phenol metabolites were inactive. Similarly, benzene-derived catechol and hydroquinone, but not phenol, induce apoptosis in HBMP cells [Moran et al., Mol. Pharmacol., 50 (1996) 610-615]. We propose that remoxipride and benzene may induce aplastic anemia via production of similar reactive metabolites and that the ability of NCQ436 and NCQ344 to induce apoptosis in HBMP cells may contribute to the mechanism underlying acquired aplastic anemia that has been associated with remoxipride.","[{'text': 'remoxipride', 'type': 'Chemical', 'start': 26, 'end': 37, 'mesh': 'D017330'}, {'text': 'remoxipride', 'type': 'Chemical', 'start': 133, 'end': 144, 'mesh': 'D017330'}, {'text': 'aplastic anemia', 'type': 'Disease', 'start': 153, 'end': 168, 'mesh': 'D000741'}, {'text': 'remoxipride', 'type': 'Chemical', 'start': 195, 'end': 206, 'mesh': 'D017330'}, {'text': '(S)-(-)-3-bromo-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2,6-dimethoxybenz amide', 'type': 'Chemical', 'start': 208, 'end': 282, 'mesh': 'D017330'}, {'text': 'aplastic anemia', 'type': 'Disease', 'start': 318, 'end': 333, 'mesh': 'D000741'}, {'text': 'remoxipride', 'type': 'Chemical', 'start': 367, 'end': 378, 'mesh': 'D017330'}, {'text': 'pyrrolidine', 'type': 'Chemical', 'start': 386, 'end': 397, 'mesh': 'C032519'}, {'text': 'Hoechst 33342', 'type': 'Chemical', 'start': 672, 'end': 685, 'mesh': 'C017807'}, {'text': 'propidium iodide', 'type': 'Chemical', 'start': 691, 'end': 707, 'mesh': 'D011419'}, {'text': 'catechol', 'type': 'Chemical', 'start': 923, 'end': 931, 'mesh': 'C034221'}, {'text': 'hydroquinone', 'type': 'Chemical', 'start': 936, 'end': 948, 'mesh': 'C031927'}, {'text': 'NCQ436', 'type': 'Chemical', 'start': 962, 'end': 968, 'mesh': 'C084325'}, {'text': 'NCQ344', 'type': 'Chemical', 'start': 973, 'end': 979, 'mesh': 'C112341'}, {'text': 'phenols', 'type': 'Chemical', 'start': 1079, 'end': 1086, 'mesh': 'D010636'}, {'text': 'FLA797', 'type': 'Chemical', 'start': 1108, 'end': 1114, 'mesh': 'C050313'}, {'text': 'pyrrolidine', 'type': 'Chemical', 'start': 1163, 'end': 1174, 'mesh': 'C032519'}, {'text': 'necrosis', 'type': 'Disease', 'start': 1227, 'end': 1235, 'mesh': 'D009336'}, {'text': 'NCQ436', 'type': 'Chemical', 'start': 1271, 'end': 1277, 'mesh': 'C084325'}, {'text': 'NCQ344', 'type': 'Chemical', 'start': 1282, 'end': 1288, 'mesh': 'C112341'}, {'text': 'necrosis', 'type': 'Disease', 'start': 1378, 'end': 1386, 'mesh': 'D009336'}, {'text': 'catechol', 'type': 'Chemical', 'start': 1438, 'end': 1446, 'mesh': 'C034221'}, {'text': 'hydroquinone', 'type': 'Chemical', 'start': 1451, 'end': 1463, 'mesh': 'C031927'}, {'text': 'remoxipride', 'type': 'Chemical', 'start': 1479, 'end': 1490, 'mesh': 'D017330'}, {'text': 'phenol', 'type': 'Chemical', 'start': 1573, 'end': 1579, 'mesh': 'D019800'}, {'text': 'benzene', 'type': 'Chemical', 'start': 1618, 'end': 1625, 'mesh': 'D001554'}, {'text': 'catechol', 'type': 'Chemical', 'start': 1634, 'end': 1642, 'mesh': 'C034221'}, {'text': 'hydroquinone', 'type': 'Chemical', 'start': 1647, 'end': 1659, 'mesh': 'C031927'}, {'text': 'phenol', 'type': 'Chemical', 'start': 1669, 'end': 1675, 'mesh': 'D019800'}, {'text': 'remoxipride', 'type': 'Chemical', 'start': 1776, 'end': 1787, 'mesh': 'D017330'}, {'text': 'benzene', 'type': 'Chemical', 'start': 1792, 'end': 1799, 'mesh': 'D001554'}, {'text': 'aplastic anemia', 'type': 'Disease', 'start': 1811, 'end': 1826, 'mesh': 'D000741'}, {'text': 'NCQ436', 'type': 'Chemical', 'start': 1898, 'end': 1904, 'mesh': 'C084325'}, {'text': 'NCQ344', 'type': 'Chemical', 'start': 1909, 'end': 1915, 'mesh': 'C112341'}, {'text': 'aplastic anemia', 'type': 'Disease', 'start': 2002, 'end': 2017, 'mesh': 'D000741'}, {'text': 'remoxipride', 'type': 'Chemical', 'start': 2048, 'end': 2059, 'mesh': 'D017330'}]"
+1326,10510854,"Synthesis and preliminary pharmacological investigations of 1-(1,2-dihydro-2-acenaphthylenyl)piperazine derivatives as potential atypical antipsychotic agents in mice.","In research towards the development of new atypical antipsychotic agents, one strategy is that the dopaminergic system can be modulated through manipulation of the serotonergic system. The synthesis and preliminary pharmacological evaluation of a series of potential atypical antipsychotic agents based on the structure of 1-(1,2-dihydro-2-acenaphthylenyl)piperazine (7) is described. Compound 7e, 5-{2-[4-(1,2-dihydro-2-acenaphthylenyl)piperazinyl]ethyl}-2,3-dihy dro-1H- indol-2-one, from this series showed significant affinities at the 5-HT1A and 5-HT2A receptors and moderate affinity at the D2 receptor. 7e exhibits a high reversal of catalepsy induced by haloperidol indicating its atypical antipsychotic nature.","[{'text': '1-(1,2-dihydro-2-acenaphthylenyl)piperazine', 'type': 'Chemical', 'start': 60, 'end': 103, 'mesh': '-1'}, {'text': '1-(1,2-dihydro-2-acenaphthylenyl)piperazine', 'type': 'Chemical', 'start': 491, 'end': 534, 'mesh': '-1'}, {'text': '5-{2-[4-(1,2-dihydro-2-acenaphthylenyl)piperazinyl]ethyl}-2,3-dihy dro-1H- indol-2-one', 'type': 'Chemical', 'start': 566, 'end': 652, 'mesh': '-1'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 809, 'end': 818, 'mesh': 'D002375'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 830, 'end': 841, 'mesh': 'D006220'}]"
+1327,10672628,Sub-chronic inhibition of nitric-oxide synthesis modifies haloperidol-induced catalepsy and the number of NADPH-diaphorase neurons in mice.,"RATIONALE: NG-nitro-L-arginine (L-NOARG), an inhibitor of nitric-oxide synthase (NOS), induces catalepsy in mice. This effect undergoes rapid tolerance, showing a significant decrease after 2 days of sub-chronic L-NOARG treatment. Nitric oxide (NO) has been shown to influence dopaminergic neurotransmission in the striatum. Neuroleptic drugs such as haloperidol, which block dopamine receptors, also cause catalepsy in rodents. OBJECTIVES: To investigate the effects of subchronic L-NOARG treatment in haloperidol-induced catalepsy and the number of NOS neurons in areas related to motor control. METHODS: Male albino Swiss mice were treated sub-chronically (twice a day for 4 days) with L-NOARG (40 mg/kg i.p.) or haloperidol (1 mg/kg i.p.). Catalepsy was evaluated at the beginning and the end of the treatments. Reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry was also employed to visualize NOS as an index of enzyme expression in mice brain regions related to motor control. RESULTS: L-NOARG sub-chronic administration produced tolerance of L-NOARG and of haloperidol-induced catalepsy. It also induced an increase in the number of NADPH-d-positive cells in the dorsal part of the caudate and accumbens nuclei compared with haloperidol and in the pedunculopontine tegmental nucleus compared with saline. In contrast, there was a decrease in NADPH-d neuron number in the substantia nigra, pars compacta in both haloperidol-treated and L-NOARG-treated animals. CONCLUSIONS: The results give further support to the hypothesis that NO plays a role in motor behavior control and suggest that it may take part in the synaptic changes produced by antipsychotic treatment.","[{'text': 'nitric-oxide', 'type': 'Chemical', 'start': 26, 'end': 38, 'mesh': 'D009569'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 58, 'end': 69, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 78, 'end': 87, 'mesh': 'D002375'}, {'text': 'NADPH', 'type': 'Chemical', 'start': 106, 'end': 111, 'mesh': 'D009249'}, {'text': 'NG-nitro-L-arginine', 'type': 'Chemical', 'start': 151, 'end': 170, 'mesh': 'D019335'}, {'text': 'L-NOARG', 'type': 'Chemical', 'start': 172, 'end': 179, 'mesh': 'D019335'}, {'text': 'nitric-oxide', 'type': 'Chemical', 'start': 198, 'end': 210, 'mesh': 'D009569'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 235, 'end': 244, 'mesh': 'D002375'}, {'text': 'L-NOARG', 'type': 'Chemical', 'start': 352, 'end': 359, 'mesh': 'D019335'}, {'text': 'Nitric oxide', 'type': 'Chemical', 'start': 371, 'end': 383, 'mesh': 'D009569'}, {'text': 'NO', 'type': 'Chemical', 'start': 385, 'end': 387, 'mesh': 'D009569'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 491, 'end': 502, 'mesh': 'D006220'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 516, 'end': 524, 'mesh': 'D004298'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 547, 'end': 556, 'mesh': 'D002375'}, {'text': 'L-NOARG', 'type': 'Chemical', 'start': 622, 'end': 629, 'mesh': 'D019335'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 643, 'end': 654, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 663, 'end': 672, 'mesh': 'D002375'}, {'text': 'L-NOARG', 'type': 'Chemical', 'start': 829, 'end': 836, 'mesh': 'D019335'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 856, 'end': 867, 'mesh': 'D006220'}, {'text': 'Catalepsy', 'type': 'Disease', 'start': 884, 'end': 893, 'mesh': 'D002375'}, {'text': 'nicotinamide adenine dinucleotide phosphate', 'type': 'Chemical', 'start': 964, 'end': 1007, 'mesh': 'D009249'}, {'text': 'NADPH', 'type': 'Chemical', 'start': 1020, 'end': 1025, 'mesh': 'D009249'}, {'text': 'L-NOARG', 'type': 'Chemical', 'start': 1169, 'end': 1176, 'mesh': 'D019335'}, {'text': 'L-NOARG', 'type': 'Chemical', 'start': 1226, 'end': 1233, 'mesh': 'D019335'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1241, 'end': 1252, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 1261, 'end': 1270, 'mesh': 'D002375'}, {'text': 'NADPH', 'type': 'Chemical', 'start': 1317, 'end': 1322, 'mesh': 'D009249'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1409, 'end': 1420, 'mesh': 'D006220'}, {'text': 'NADPH', 'type': 'Chemical', 'start': 1526, 'end': 1531, 'mesh': 'D009249'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1595, 'end': 1606, 'mesh': 'D006220'}, {'text': 'L-NOARG', 'type': 'Chemical', 'start': 1619, 'end': 1626, 'mesh': 'D019335'}, {'text': 'NO', 'type': 'Chemical', 'start': 1713, 'end': 1715, 'mesh': 'D009569'}]"
+1328,10677406,Prolonged left ventricular dysfunction occurs in patients with coronary artery disease after both dobutamine and exercise induced myocardial ischaemia.,"OBJECTIVE: To determine whether pharmacological stress leads to prolonged but reversible left ventricular dysfunction in patients with coronary artery disease, similar to that seen after exercise. DESIGN: A randomised crossover study of recovery time of systolic and diastolic left ventricular function after exercise and dobutamine induced ischaemia. SUBJECTS: 10 patients with stable angina, angiographically proven coronary artery disease, and normal left ventricular function. INTERVENTIONS: Treadmill exercise and dobutamine stress were performed on different days. Quantitative assessment of systolic and diastolic left ventricular function was performed using transthoracic echocardiography at baseline and at regular intervals after each test. RESULTS: Both forms of stress led to prolonged but reversible systolic and diastolic dysfunction. There was no difference in the maximum double product (p = 0.53) or ST depression (p = 0.63) with either form of stress. After exercise, ejection fraction was reduced at 15 and 30 minutes compared with baseline (mean (SEM), -5.6 (1.5)%, p < 0.05; and -6.1 (2.2)%, p < 0. 01), and at 30 and 45 minutes after dobutamine (-10.8 (1.8)% and -5. 5 (1.8)%, both p < 0.01). Regional analysis showed a reduction in the worst affected segment 15 and 30 minutes after exercise (-27.9 (7.2)% and -28.6 (5.7)%, both p < 0.01), and at 30 minutes after dobutamine (-32 (5.3)%, p < 0.01). The isovolumic relaxation period was prolonged 45 minutes after each form of stress (p < 0.05). CONCLUSIONS: In patients with coronary artery disease, dobutamine induced ischaemia results in prolonged reversible left ventricular dysfunction, presumed to be myocardial stunning, similar to that seen after exercise. Dobutamine induced ischaemia could therefore be used to study the pathophysiology of this phenomenon further in patients with coronary artery disease.","[{'text': 'left ventricular dysfunction', 'type': 'Disease', 'start': 10, 'end': 38, 'mesh': 'D018487'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 63, 'end': 86, 'mesh': 'D003324'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 98, 'end': 108, 'mesh': 'D004280'}, {'text': 'myocardial ischaemia', 'type': 'Disease', 'start': 130, 'end': 150, 'mesh': 'D017202'}, {'text': 'left ventricular dysfunction', 'type': 'Disease', 'start': 241, 'end': 269, 'mesh': 'D018487'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 287, 'end': 310, 'mesh': 'D003324'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 474, 'end': 484, 'mesh': 'D004280'}, {'text': 'ischaemia', 'type': 'Disease', 'start': 493, 'end': 502, 'mesh': 'D007511'}, {'text': 'stable angina', 'type': 'Disease', 'start': 531, 'end': 544, 'mesh': 'D060050'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 570, 'end': 593, 'mesh': 'D003324'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 671, 'end': 681, 'mesh': 'D004280'}, {'text': 'depression', 'type': 'Disease', 'start': 1073, 'end': 1083, 'mesh': 'D003866'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 1309, 'end': 1319, 'mesh': 'D004280'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 1540, 'end': 1550, 'mesh': 'D004280'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 1701, 'end': 1724, 'mesh': 'D003324'}, {'text': 'dobutamine', 'type': 'Chemical', 'start': 1726, 'end': 1736, 'mesh': 'D004280'}, {'text': 'ischaemia', 'type': 'Disease', 'start': 1745, 'end': 1754, 'mesh': 'D007511'}, {'text': 'left ventricular dysfunction', 'type': 'Disease', 'start': 1787, 'end': 1815, 'mesh': 'D018487'}, {'text': 'myocardial stunning', 'type': 'Disease', 'start': 1832, 'end': 1851, 'mesh': 'D017682'}, {'text': 'Dobutamine', 'type': 'Chemical', 'start': 1890, 'end': 1900, 'mesh': 'D004280'}, {'text': 'ischaemia', 'type': 'Disease', 'start': 1909, 'end': 1918, 'mesh': 'D007511'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 2016, 'end': 2039, 'mesh': 'D003324'}]"
+1329,10713017,Anorexigens and pulmonary hypertension in the United States: results from the surveillance of North American pulmonary hypertension.,"BACKGROUND: The use of appetite suppressants in Europe has been associated with the development of primary pulmonary hypertension (PPH). Recently, fenfluramine appetite suppressants became widely used in the United States but were withdrawn in September 1997 because of concerns over adverse effects. MATERIALS AND METHODS: We conducted a prospective surveillance study on patients diagnosed with pulmonary hypertension at 12 large referral centers in North America. Data collected on patients seen from September 1, 1996, to December 31, 1997, included the cause of the pulmonary hypertension and its severity. Patients with no identifiable cause of pulmonary hypertension were classed as PPH. A history of drug exposure also was taken with special attention on the use of antidepressants, anorexigens, and amphetamines. RESULTS: Five hundred seventy-nine patients were studied, 205 with PPH and 374 with pulmonary hypertension from other causes (secondary pulmonary hypertension [SPH]). The use of anorexigens was common in both groups. However, of the medications surveyed, only the fenfluramines had a significant preferential association with PPH as compared with SPH (adjusted odds ratio for use > 6 months, 7.5; 95% confidence interval, 1.7 to 32.4). The association was stronger with longer duration of use when compared to shorter duration of use and was more pronounced in recent users than in remote users. An unexpectedly high (11.4%) number of patients with SPH had used anorexigens. CONCLUSION: The magnitude of the association with PPH, the increase of association with increasing duration of use, and the specificity for fenfluramines are consistent with previous studies indicating that fenfluramines are causally related to PPH. The high prevalence of anorexigen use in patients with SPH also raises the possibility that these drugs precipitate pulmonary hypertension in patients with underlying conditions associated with SPH.","[{'text': 'pulmonary hypertension', 'type': 'Disease', 'start': 16, 'end': 38, 'mesh': 'D006976'}, {'text': 'pulmonary hypertension', 'type': 'Disease', 'start': 109, 'end': 131, 'mesh': 'D006976'}, {'text': 'primary pulmonary hypertension', 'type': 'Disease', 'start': 232, 'end': 262, 'mesh': 'D006976'}, {'text': 'PPH', 'type': 'Disease', 'start': 264, 'end': 267, 'mesh': 'D006976'}, {'text': 'fenfluramine', 'type': 'Chemical', 'start': 280, 'end': 292, 'mesh': 'D005277'}, {'text': 'pulmonary hypertension', 'type': 'Disease', 'start': 530, 'end': 552, 'mesh': 'D006976'}, {'text': 'pulmonary hypertension', 'type': 'Disease', 'start': 704, 'end': 726, 'mesh': 'D006976'}, {'text': 'pulmonary hypertension', 'type': 'Disease', 'start': 784, 'end': 806, 'mesh': 'D006976'}, {'text': 'PPH', 'type': 'Disease', 'start': 823, 'end': 826, 'mesh': 'D006976'}, {'text': 'amphetamines', 'type': 'Chemical', 'start': 941, 'end': 953, 'mesh': 'D000662'}, {'text': 'PPH', 'type': 'Disease', 'start': 1022, 'end': 1025, 'mesh': 'D006976'}, {'text': 'pulmonary hypertension', 'type': 'Disease', 'start': 1039, 'end': 1061, 'mesh': 'D006976'}, {'text': 'pulmonary hypertension', 'type': 'Disease', 'start': 1091, 'end': 1113, 'mesh': 'D006976'}, {'text': 'fenfluramines', 'type': 'Chemical', 'start': 1219, 'end': 1232, 'mesh': 'D005277'}, {'text': 'PPH', 'type': 'Disease', 'start': 1281, 'end': 1284, 'mesh': 'D006976'}, {'text': 'PPH', 'type': 'Disease', 'start': 1680, 'end': 1683, 'mesh': 'D006976'}, {'text': 'fenfluramines', 'type': 'Chemical', 'start': 1770, 'end': 1783, 'mesh': 'D005277'}, {'text': 'fenfluramines', 'type': 'Chemical', 'start': 1837, 'end': 1850, 'mesh': 'D005277'}, {'text': 'PPH', 'type': 'Disease', 'start': 1875, 'end': 1878, 'mesh': 'D006976'}, {'text': 'pulmonary hypertension', 'type': 'Disease', 'start': 1996, 'end': 2018, 'mesh': 'D006976'}]"
+1330,10726030,Clinical aspects of heparin-induced thrombocytopenia and thrombosis and other side effects of heparin therapy.,"Heparin, first used to prevent the clotting of blood in vitro, has been clinically used to treat thrombosis for more than 50 years. Although several new anticoagulant drugs are in development, heparin remains the anticoagulant of choice to treat acute thrombotic episodes. The clinical effects of heparin are meritorious, but side effects do exist. Bleeding is the primary untoward effect of heparin. Major bleeding is of primary concern in patients receiving heparin therapy. However, additional important untoward effects of heparin therapy include heparin-induced thrombocytopenia, heparin-associated osteoporosis, eosinophilia, skin reactions, allergic reactions other than thrombocytopenia, alopecia, transaminasemia, hyperkalemia, hypoaldosteronism, and priapism. These side effects are relatively rare in a given individual, but given the extremely widespread use of heparin, some are quite common, particularly HITT and osteoporosis. Although reasonable incidences of many of these side effects can be ""softly"" deduced from current reports dealing with unfractionated heparin, at present the incidences of these side effects with newer low molecular weight heparins appear to be much less common. However, only longer experience will more clearly define the incidence of each side effect with low molecular weight preparations.","[{'text': 'heparin', 'type': 'Chemical', 'start': 20, 'end': 27, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 36, 'end': 52, 'mesh': 'D013921'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 57, 'end': 67, 'mesh': 'D013927'}, {'text': 'heparin', 'type': 'Chemical', 'start': 94, 'end': 101, 'mesh': 'D006493'}, {'text': 'Heparin', 'type': 'Chemical', 'start': 111, 'end': 118, 'mesh': 'D006493'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 208, 'end': 218, 'mesh': 'D013927'}, {'text': 'heparin', 'type': 'Chemical', 'start': 304, 'end': 311, 'mesh': 'D006493'}, {'text': 'thrombotic', 'type': 'Disease', 'start': 363, 'end': 373, 'mesh': 'D013927'}, {'text': 'heparin', 'type': 'Chemical', 'start': 408, 'end': 415, 'mesh': 'D006493'}, {'text': 'Bleeding', 'type': 'Disease', 'start': 460, 'end': 468, 'mesh': 'D006470'}, {'text': 'heparin', 'type': 'Chemical', 'start': 503, 'end': 510, 'mesh': 'D006493'}, {'text': 'bleeding', 'type': 'Disease', 'start': 518, 'end': 526, 'mesh': 'D006470'}, {'text': 'heparin', 'type': 'Chemical', 'start': 571, 'end': 578, 'mesh': 'D006493'}, {'text': 'heparin', 'type': 'Chemical', 'start': 638, 'end': 645, 'mesh': 'D006493'}, {'text': 'heparin', 'type': 'Chemical', 'start': 662, 'end': 669, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 678, 'end': 694, 'mesh': 'D013921'}, {'text': 'heparin', 'type': 'Chemical', 'start': 696, 'end': 703, 'mesh': 'D006493'}, {'text': 'osteoporosis', 'type': 'Disease', 'start': 715, 'end': 727, 'mesh': 'D010024'}, {'text': 'eosinophilia', 'type': 'Disease', 'start': 729, 'end': 741, 'mesh': 'D004802'}, {'text': 'skin reactions', 'type': 'Disease', 'start': 743, 'end': 757, 'mesh': 'D012871'}, {'text': 'allergic reactions', 'type': 'Disease', 'start': 759, 'end': 777, 'mesh': 'D004342'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 789, 'end': 805, 'mesh': 'D013921'}, {'text': 'alopecia', 'type': 'Disease', 'start': 807, 'end': 815, 'mesh': 'D000505'}, {'text': 'hyperkalemia', 'type': 'Disease', 'start': 834, 'end': 846, 'mesh': 'D006947'}, {'text': 'hypoaldosteronism', 'type': 'Disease', 'start': 848, 'end': 865, 'mesh': 'D006994'}, {'text': 'priapism', 'type': 'Disease', 'start': 871, 'end': 879, 'mesh': 'D011317'}, {'text': 'heparin', 'type': 'Chemical', 'start': 985, 'end': 992, 'mesh': 'D006493'}, {'text': 'HITT', 'type': 'Disease', 'start': 1030, 'end': 1034, 'mesh': 'D013921|D013927'}, {'text': 'osteoporosis', 'type': 'Disease', 'start': 1039, 'end': 1051, 'mesh': 'D010024'}, {'text': 'heparin', 'type': 'Chemical', 'start': 1187, 'end': 1194, 'mesh': 'D006493'}, {'text': 'heparins', 'type': 'Chemical', 'start': 1276, 'end': 1284, 'mesh': 'D006493'}]"
+1331,10764869,A case of bilateral optic neuropathy in a patient on tacrolimus (FK506) therapy after liver transplantation.,"PURPOSE: To report a case of bilateral optic neuropathy in a patient receiving tacrolimus (FK 506, Prograf; Fujisawa USA, Inc, Deerfield, Illinois) for immunosuppression after orthotropic liver transplantation. METHOD: Case report. In a 58-year-old man receiving tacrolimus after orthotropic liver transplantation, serial neuro-ophthalmologic examinations and laboratory studies were performed. RESULTS: The patient had episodic deterioration of vision in both eyes, with clinical features resembling ischemic optic neuropathies. Deterioration of vision occurred despite discontinuation of the tacrolimus. CONCLUSION: Tacrolimus and other immunosuppressive agents may be associated with optic nerve toxicity.","[{'text': 'optic neuropathy', 'type': 'Disease', 'start': 20, 'end': 36, 'mesh': 'D009901'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 53, 'end': 63, 'mesh': 'D016559'}, {'text': 'FK506', 'type': 'Chemical', 'start': 65, 'end': 70, 'mesh': 'D016559'}, {'text': 'optic neuropathy', 'type': 'Disease', 'start': 148, 'end': 164, 'mesh': 'D009901'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 188, 'end': 198, 'mesh': 'D016559'}, {'text': 'FK 506', 'type': 'Chemical', 'start': 200, 'end': 206, 'mesh': 'D016559'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 372, 'end': 382, 'mesh': 'D016559'}, {'text': 'ischemic optic neuropathies', 'type': 'Disease', 'start': 610, 'end': 637, 'mesh': 'D018917'}, {'text': 'Deterioration of vision', 'type': 'Disease', 'start': 639, 'end': 662, 'mesh': 'D015354'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 703, 'end': 713, 'mesh': 'D016559'}, {'text': 'Tacrolimus', 'type': 'Chemical', 'start': 727, 'end': 737, 'mesh': 'D016559'}, {'text': 'optic nerve toxicity', 'type': 'Disease', 'start': 796, 'end': 816, 'mesh': 'D009901'}]"
+1332,10770468,"Hypercalcemia, arrhythmia, and mood stabilizers.","Recent findings in a bipolar patient receiving maintenance lithium therapy who developed hypercalcemia and severe bradyarrhythmia prompted the authors to conduct a retrospective study of bipolar patients with lithium-associated hypercalcemia. A printout of all cases of hypercalcemia that presented during a 1-year period was generated. After eliminating spurious hypercalcemias or those associated with intravenous fluids, the authors identified 18 non-lithium-treated patients with hypercalcemias related to malignancies and other medical conditions (group A) and 12 patients with lithium-associated hypercalcemia (group B). Patients in group B were not comparable to those in group A, as the latter were medically compromised and were receiving multiple pharmacotherapies. Thus, two control groups were generated: group C1, which included age- and sex-comparable lithium-treated bipolar normocalcemic patients, and group C2, which included bipolar normocalcemic patients treated with anticonvulsant mood stabilizers. The electrocardiographic (ECG) findings for patients in group B were compared with those of patients in groups C1 and C2. It was found that these groups did not differ in their overall frequency of ECG abnormalities; however, there were significant differences in the frequency of conduction defects. Patients with hypercalcemia resulting from medical diseases and bipolar patients with lithium-associated hypercalcemia had significantly higher frequencies of conduction defects. Patients in group A had significant mortality at 2-year follow-up (28%), in contrast to zero mortality in the other three groups. The clinical implications of these findings are discussed.","[{'text': 'Hypercalcemia', 'type': 'Disease', 'start': 0, 'end': 13, 'mesh': 'D006934'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 15, 'end': 25, 'mesh': 'D001145'}, {'text': 'bipolar', 'type': 'Disease', 'start': 70, 'end': 77, 'mesh': 'D001714'}, {'text': 'lithium', 'type': 'Chemical', 'start': 108, 'end': 115, 'mesh': 'D008094'}, {'text': 'hypercalcemia', 'type': 'Disease', 'start': 138, 'end': 151, 'mesh': 'D006934'}, {'text': 'bradyarrhythmia', 'type': 'Disease', 'start': 163, 'end': 178, 'mesh': 'D001919'}, {'text': 'bipolar', 'type': 'Disease', 'start': 236, 'end': 243, 'mesh': 'D001714'}, {'text': 'lithium', 'type': 'Chemical', 'start': 258, 'end': 265, 'mesh': 'D008094'}, {'text': 'hypercalcemia', 'type': 'Disease', 'start': 277, 'end': 290, 'mesh': 'D006934'}, {'text': 'hypercalcemia', 'type': 'Disease', 'start': 319, 'end': 332, 'mesh': 'D006934'}, {'text': 'hypercalcemias', 'type': 'Disease', 'start': 413, 'end': 427, 'mesh': 'D006934'}, {'text': 'lithium', 'type': 'Chemical', 'start': 503, 'end': 510, 'mesh': 'D008094'}, {'text': 'hypercalcemias', 'type': 'Disease', 'start': 533, 'end': 547, 'mesh': 'D006934'}, {'text': 'malignancies', 'type': 'Disease', 'start': 559, 'end': 571, 'mesh': 'D009369'}, {'text': 'lithium', 'type': 'Chemical', 'start': 632, 'end': 639, 'mesh': 'D008094'}, {'text': 'hypercalcemia', 'type': 'Disease', 'start': 651, 'end': 664, 'mesh': 'D006934'}, {'text': 'lithium', 'type': 'Chemical', 'start': 915, 'end': 922, 'mesh': 'D008094'}, {'text': 'bipolar', 'type': 'Disease', 'start': 931, 'end': 938, 'mesh': 'D001714'}, {'text': 'bipolar', 'type': 'Disease', 'start': 992, 'end': 999, 'mesh': 'D001714'}, {'text': 'hypercalcemia', 'type': 'Disease', 'start': 1384, 'end': 1397, 'mesh': 'D006934'}, {'text': 'bipolar', 'type': 'Disease', 'start': 1434, 'end': 1441, 'mesh': 'D001714'}, {'text': 'lithium', 'type': 'Chemical', 'start': 1456, 'end': 1463, 'mesh': 'D008094'}, {'text': 'hypercalcemia', 'type': 'Disease', 'start': 1475, 'end': 1488, 'mesh': 'D006934'}]"
+1333,10933650,Attenuation of nephrotoxicity by a novel lipid nanosphere (NS-718) incorporating amphotericin B.,"NS-718, a lipid nanosphere incorporating amphotericin B, is effective against pathogenic fungi and has low toxicity. We compared the toxicity of NS-718 with that of Fungizone (amphotericin B-sodium deoxycholate; D-AmB) in vitro using renal cell cultures and in vivo by biochemical analysis, histopathological study of the kidney and pharmacokinetic study of amphotericin B following intravenous infusion of the formulation in rats. Incubation with NS-718 resulted in significantly less damage of cultured human renal proximal tubular epithelial cells compared with D-AmB. Serum blood urea and creatinine concentrations increased significantly in rats given an iv infusion of D-AmB 3 mg/kg but not in those given the same dose of NS-718. Histopathological examination of the kidney showed tubular necrosis in D-AmB-treated rats but no change in NS-718-treated rats. Amphotericin B concentrations in the kidney in NS-718-treated rats were higher than those in D-AmB-treated rats. Our in vitro and in vivo results suggest that incorporation of amphotericin B into lipid nanospheres of NS-718 attenuates the nephrotoxicity of amphotericin B.","[{'text': 'nephrotoxicity', 'type': 'Disease', 'start': 15, 'end': 29, 'mesh': 'D007674'}, {'text': 'amphotericin B', 'type': 'Chemical', 'start': 81, 'end': 95, 'mesh': 'D000666'}, {'text': 'amphotericin B', 'type': 'Chemical', 'start': 138, 'end': 152, 'mesh': 'D000666'}, {'text': 'toxicity', 'type': 'Disease', 'start': 204, 'end': 212, 'mesh': 'D064420'}, {'text': 'toxicity', 'type': 'Disease', 'start': 230, 'end': 238, 'mesh': 'D064420'}, {'text': 'Fungizone', 'type': 'Chemical', 'start': 262, 'end': 271, 'mesh': 'D000666'}, {'text': 'amphotericin B-sodium deoxycholate', 'type': 'Chemical', 'start': 273, 'end': 307, 'mesh': 'C059765'}, {'text': 'D-AmB', 'type': 'Chemical', 'start': 309, 'end': 314, 'mesh': 'C059765'}, {'text': 'amphotericin B', 'type': 'Chemical', 'start': 455, 'end': 469, 'mesh': 'D000666'}, {'text': 'D-AmB', 'type': 'Chemical', 'start': 662, 'end': 667, 'mesh': 'C059765'}, {'text': 'urea', 'type': 'Chemical', 'start': 681, 'end': 685, 'mesh': 'D014508'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 690, 'end': 700, 'mesh': 'D003404'}, {'text': 'D-AmB', 'type': 'Chemical', 'start': 772, 'end': 777, 'mesh': 'C059765'}, {'text': 'tubular necrosis', 'type': 'Disease', 'start': 885, 'end': 901, 'mesh': 'D007683'}, {'text': 'D-AmB', 'type': 'Chemical', 'start': 905, 'end': 910, 'mesh': 'C059765'}, {'text': 'Amphotericin B', 'type': 'Chemical', 'start': 962, 'end': 976, 'mesh': 'D000666'}, {'text': 'D-AmB', 'type': 'Chemical', 'start': 1055, 'end': 1060, 'mesh': 'C059765'}, {'text': 'amphotericin B', 'type': 'Chemical', 'start': 1138, 'end': 1152, 'mesh': 'D000666'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1201, 'end': 1215, 'mesh': 'D007674'}, {'text': 'amphotericin B', 'type': 'Chemical', 'start': 1219, 'end': 1233, 'mesh': 'D000666'}]"
+1334,10939760,Patterns of sulfadiazine acute nephrotoxicity.,"Sulfadiazine acute nephrotoxicity is reviving specially because of its use in toxoplasmosis in HIV-positive patients. We report 4 cases, one of them in a previously healthy person. Under treatment with sulfadiazine they developed oliguria, abdominal pain, renal failure and showed multiple radiolucent renal calculi in echography. All patients recovered their previous normal renal function after adequate hydration and alcalinization. A nephrostomy tube had to be placed in one of the patients for ureteral lithiasis in a single functional kidney. None of them needed dialysis or a renal biopsy because of a typical benign course. Treatment with sulfadiazine requires exquisite control of renal function, an increase in water ingestion and possibly the alcalinization of the urine. We communicate a case in a previously healthy person, a fact not found in the recent literature. Probably many more cases are not detected. We think that a prospective study would be useful.","[{'text': 'sulfadiazine', 'type': 'Chemical', 'start': 12, 'end': 24, 'mesh': 'D013411'}, {'text': 'acute nephrotoxicity', 'type': 'Disease', 'start': 25, 'end': 45, 'mesh': 'D058186'}, {'text': 'Sulfadiazine', 'type': 'Chemical', 'start': 47, 'end': 59, 'mesh': 'D013411'}, {'text': 'acute nephrotoxicity', 'type': 'Disease', 'start': 60, 'end': 80, 'mesh': 'D058186'}, {'text': 'toxoplasmosis', 'type': 'Disease', 'start': 125, 'end': 138, 'mesh': 'D014123'}, {'text': 'sulfadiazine', 'type': 'Chemical', 'start': 249, 'end': 261, 'mesh': 'D013411'}, {'text': 'oliguria', 'type': 'Disease', 'start': 277, 'end': 285, 'mesh': 'D009846'}, {'text': 'abdominal pain', 'type': 'Disease', 'start': 287, 'end': 301, 'mesh': 'D015746'}, {'text': 'renal failure', 'type': 'Disease', 'start': 303, 'end': 316, 'mesh': 'D051437'}, {'text': 'renal calculi', 'type': 'Disease', 'start': 349, 'end': 362, 'mesh': 'D007669'}, {'text': 'ureteral lithiasis', 'type': 'Disease', 'start': 546, 'end': 564, 'mesh': 'D052878'}, {'text': 'sulfadiazine', 'type': 'Chemical', 'start': 694, 'end': 706, 'mesh': 'D013411'}]"
+1335,10960401,Downbeat nystagmus associated with intravenous patient-controlled administration of morphine.,"IMPLICATIONS: This case documents a patient who developed dizziness with downbeating nystagmus while receiving a relatively large dose of IV patient-controlled analgesia morphine. Although there have been case reports of epidural morphine with these symptoms and signs, this has not been previously documented with IV or patient-controlled analgesia morphine.","[{'text': 'Downbeat nystagmus', 'type': 'Disease', 'start': 0, 'end': 18, 'mesh': 'D009759'}, {'text': 'morphine', 'type': 'Chemical', 'start': 84, 'end': 92, 'mesh': 'D009020'}, {'text': 'dizziness', 'type': 'Disease', 'start': 152, 'end': 161, 'mesh': 'D004244'}, {'text': 'downbeating nystagmus', 'type': 'Disease', 'start': 167, 'end': 188, 'mesh': 'D009759'}, {'text': 'morphine', 'type': 'Chemical', 'start': 264, 'end': 272, 'mesh': 'D009020'}, {'text': 'morphine', 'type': 'Chemical', 'start': 324, 'end': 332, 'mesh': 'D009020'}, {'text': 'morphine', 'type': 'Chemical', 'start': 444, 'end': 452, 'mesh': 'D009020'}]"
+1336,10975596,Hemodynamic and antiadrenergic effects of dronedarone and amiodarone in animals with a healed myocardial infarction.,"The hemodynamic and antiadrenergic effects of dronedarone, a noniodinated compound structurally related to amiodarone, were compared with those of amiodarone after prolonged oral administration, both at rest and during sympathetic stimulation in conscious dogs with a healed myocardial infarction. All dogs (n = 6) randomly received orally dronedarone (10 and 30 mg/kg), amiodarone (10 and 30 mg/kg), and placebo twice daily for 7 days, with a 3-week washout between consecutive treatments. Heart rate (HR), mean arterial pressure (MBP), positive rate of increase of left ventricular pressure (+LVdP/dt), echocardiographically assessed left ventricular ejection fraction (LVEF), and fractional shortening (FS), as well as chronotropic response to isoproterenol and exercise-induced sympathetic stimulation were evaluated under baseline and posttreatment conditions. Resting values of LVEF, FS, +LVdP/dt, and MBP remained unchanged whatever the drug and the dosing regimen, whereas resting HR was significantly and dose-dependently lowered after dronedarone and to a lesser extent after amiodarone. Both dronedarone and amiodarone significantly reduced the exercise-induced tachycardia and, at the highest dose, decreased the isoproterenol-induced tachycardia. Thus, dronedarone and amiodarone displayed a similar level of antiadrenergic effect and did not impair the resting left ventricular function. Consequently, dronedarone might be particularly suitable for the treatment and prevention of various clinical arrhythmias, without compromising the left ventricular function.","[{'text': 'dronedarone', 'type': 'Chemical', 'start': 42, 'end': 53, 'mesh': 'C118667'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 58, 'end': 68, 'mesh': 'D000638'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 94, 'end': 115, 'mesh': 'D009203'}, {'text': 'dronedarone', 'type': 'Chemical', 'start': 163, 'end': 174, 'mesh': 'C118667'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 224, 'end': 234, 'mesh': 'D000638'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 264, 'end': 274, 'mesh': 'D000638'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 392, 'end': 413, 'mesh': 'D009203'}, {'text': 'dronedarone', 'type': 'Chemical', 'start': 457, 'end': 468, 'mesh': 'C118667'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 488, 'end': 498, 'mesh': 'D000638'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 864, 'end': 877, 'mesh': 'D007545'}, {'text': 'dronedarone', 'type': 'Chemical', 'start': 1162, 'end': 1173, 'mesh': 'C118667'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 1203, 'end': 1213, 'mesh': 'D000638'}, {'text': 'dronedarone', 'type': 'Chemical', 'start': 1220, 'end': 1231, 'mesh': 'C118667'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 1236, 'end': 1246, 'mesh': 'D000638'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 1290, 'end': 1301, 'mesh': 'D013610'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 1342, 'end': 1355, 'mesh': 'D007545'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 1364, 'end': 1375, 'mesh': 'D013610'}, {'text': 'dronedarone', 'type': 'Chemical', 'start': 1383, 'end': 1394, 'mesh': 'C118667'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 1399, 'end': 1409, 'mesh': 'D000638'}, {'text': 'dronedarone', 'type': 'Chemical', 'start': 1533, 'end': 1544, 'mesh': 'C118667'}, {'text': 'arrhythmias', 'type': 'Disease', 'start': 1629, 'end': 1640, 'mesh': 'D001145'}]"
+1337,10985896,Phase 2 trial of liposomal doxorubicin (40 mg/m(2)) in platinum/paclitaxel-refractory ovarian and fallopian tube cancers and primary carcinoma of the peritoneum.,"BACKGROUND: Several studies have demonstrated liposomal doxorubicin (Doxil) to be an active antineoplastic agent in platinum-resistant ovarian cancer, with dose limiting toxicity of the standard dosing regimen (50 mg/m(2) q 4 weeks) being severe erythrodysesthesia (""hand-foot syndrome"") and stomatitis. We wished to develop a more tolerable liposomal doxorubicin treatment regimen and document its level of activity in a well-defined patient population with platinum/paclitaxel-refractory disease. METHODS AND MATERIALS: Patients with ovarian or fallopian tube cancers or primary peritoneal carcinoma with platinum/paclitaxel-refractory disease (stable or progressive disease following treatment with these agents or previous objective response <3 months in duration) were treated with liposomal doxorubicin at a dose of 40 mg/m(2) q 4 weeks. RESULTS: A total of 49 patients (median age: 60; range 41-81) entered this phase 2 trial. The median number of prior regimens was 2 (range: 1-6). Six (12%) and 4 (8%) patients experienced grade 2 hand-foot syndrome and stomatitis, respectively (no episodes of grade 3). One patient developed grade 3 diarrhea requiring hospitalization for hydration. Six (12%) individuals required dose reductions. The median number of courses of liposomal doxorubicin administered on this protocol was 2 (range: 1-12). Four of 44 patients (9%) evaluable for response exhibited objective and subjective evidence of an antineoplastic effect of therapy. CONCLUSION: This modified liposomal doxorubicin regimen results in less toxicity (stomatitis, hand-foot syndrome) than the standard FDA-approved dose schedule. Definite, although limited, antineoplastic activity is observed in patients with well-defined platinum- and paclitaxel-refractory ovarian cancer.","[{'text': 'doxorubicin', 'type': 'Chemical', 'start': 27, 'end': 38, 'mesh': 'D004317'}, {'text': 'platinum', 'type': 'Chemical', 'start': 55, 'end': 63, 'mesh': 'D010984'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 64, 'end': 74, 'mesh': 'D017239'}, {'text': 'carcinoma of the peritoneum', 'type': 'Disease', 'start': 133, 'end': 160, 'mesh': 'D010534'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 218, 'end': 229, 'mesh': 'D004317'}, {'text': 'Doxil', 'type': 'Chemical', 'start': 231, 'end': 236, 'mesh': 'D004317'}, {'text': 'platinum', 'type': 'Chemical', 'start': 278, 'end': 286, 'mesh': 'D010984'}, {'text': 'ovarian cancer', 'type': 'Disease', 'start': 297, 'end': 311, 'mesh': 'D010051'}, {'text': 'toxicity', 'type': 'Disease', 'start': 332, 'end': 340, 'mesh': 'D064420'}, {'text': 'erythrodysesthesia', 'type': 'Disease', 'start': 408, 'end': 426, 'mesh': 'D060831'}, {'text': 'hand-foot syndrome', 'type': 'Disease', 'start': 429, 'end': 447, 'mesh': 'D060831'}, {'text': 'stomatitis', 'type': 'Disease', 'start': 454, 'end': 464, 'mesh': 'D013280'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 514, 'end': 525, 'mesh': 'D004317'}, {'text': 'platinum', 'type': 'Chemical', 'start': 621, 'end': 629, 'mesh': 'D010984'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 630, 'end': 640, 'mesh': 'D017239'}, {'text': 'peritoneal carcinoma', 'type': 'Disease', 'start': 743, 'end': 763, 'mesh': 'D010534'}, {'text': 'platinum', 'type': 'Chemical', 'start': 769, 'end': 777, 'mesh': 'D010984'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 778, 'end': 788, 'mesh': 'D017239'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 959, 'end': 970, 'mesh': 'D004317'}, {'text': 'hand-foot syndrome', 'type': 'Disease', 'start': 1202, 'end': 1220, 'mesh': 'D060831'}, {'text': 'stomatitis', 'type': 'Disease', 'start': 1225, 'end': 1235, 'mesh': 'D013280'}, {'text': 'diarrhea', 'type': 'Disease', 'start': 1306, 'end': 1314, 'mesh': 'D003967'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1446, 'end': 1457, 'mesh': 'D004317'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1677, 'end': 1688, 'mesh': 'D004317'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1713, 'end': 1721, 'mesh': 'D064420'}, {'text': 'stomatitis', 'type': 'Disease', 'start': 1723, 'end': 1733, 'mesh': 'D013280'}, {'text': 'hand-foot syndrome', 'type': 'Disease', 'start': 1735, 'end': 1753, 'mesh': 'D060831'}, {'text': 'platinum', 'type': 'Chemical', 'start': 1895, 'end': 1903, 'mesh': 'D010984'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 1909, 'end': 1919, 'mesh': 'D017239'}, {'text': 'ovarian cancer', 'type': 'Disease', 'start': 1931, 'end': 1945, 'mesh': 'D010051'}]"
+1338,10986547,"Efficacy of olanzapine in acute bipolar mania: a double-blind, placebo-controlled study. The Olanzipine HGGW Study Group.","BACKGROUND: We compared the efficacy and safety of olanzapine vs placebo for the treatment of acute bipolar mania. METHODS: Four-week, randomized, double-blind, parallel study. A total of 115 patients with a DSM-IV diagnosis of bipolar disorder, manic or mixed, were randomized to olanzapine, 5 to 20 mg/d (n = 55), or placebo (n = 60). The primary efficacy measure was the Young-Mania Rating Scale (Y-MRS) total score. Response and euthymia were defined, a priori, as at least a 50% improvement from baseline to end point and as a score of no less than 12 at end point in the Y-MRS total score, respectively. Safety was assessed using adverse events, Extrapyramidal Symptom (EPS) rating scales, laboratory values, electrocardiograms, vital signs, and weight change. RESULTS: Olanzapine-treated patients demonstrated a statistically significant greater mean (+/- SD) improvement in Y-MRS total score than placebo-treated patients (-14.8 +/- 12.5 and -8.1 +/- 12.7, respectively; P<.001), which was evident at the first postbaseline observation 1 week after randomization and was maintained throughout the study (last observation carried forward). Olanzapine-treated patients demonstrated a higher rate of response (65% vs 43%, respectively; P =.02) and euthymia (61% vs 36%, respectively; P =. 01) than placebo-treated patients. There were no statistically significant differences in EPSs between groups. However, olanzapine-treated patients had a statistically significant greater mean (+/- SD) weight gain than placebo-treated patients (2.1 +/- 2.8 vs 0.45 +/- 2.3 kg, respectively) and also experienced more treatment-emergent somnolence (21 patients [38.2%] vs 5 [8.3% ], respectively). CONCLUSION: Olanzapine demonstrated greater efficacy than placebo in the treatment of acute bipolar mania and was generally well tolerated.","[{'text': 'olanzapine', 'type': 'Chemical', 'start': 12, 'end': 22, 'mesh': 'C076029'}, {'text': 'bipolar mania', 'type': 'Disease', 'start': 32, 'end': 45, 'mesh': 'D001714'}, {'text': 'Olanzipine', 'type': 'Chemical', 'start': 93, 'end': 103, 'mesh': 'C076029'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 173, 'end': 183, 'mesh': 'C076029'}, {'text': 'bipolar mania', 'type': 'Disease', 'start': 222, 'end': 235, 'mesh': 'D001714'}, {'text': 'bipolar disorder', 'type': 'Disease', 'start': 350, 'end': 366, 'mesh': 'D001714'}, {'text': 'manic', 'type': 'Disease', 'start': 368, 'end': 373, 'mesh': 'D001714'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 403, 'end': 413, 'mesh': 'C076029'}, {'text': 'Mania', 'type': 'Disease', 'start': 502, 'end': 507, 'mesh': 'D001714'}, {'text': 'Extrapyramidal Symptom', 'type': 'Disease', 'start': 774, 'end': 796, 'mesh': 'D001480'}, {'text': 'EPS', 'type': 'Disease', 'start': 798, 'end': 801, 'mesh': 'D001480'}, {'text': 'Olanzapine', 'type': 'Chemical', 'start': 898, 'end': 908, 'mesh': 'C076029'}, {'text': 'Olanzapine', 'type': 'Chemical', 'start': 1269, 'end': 1279, 'mesh': 'C076029'}, {'text': 'EPSs', 'type': 'Disease', 'start': 1506, 'end': 1510, 'mesh': 'D001480'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 1536, 'end': 1546, 'mesh': 'C076029'}, {'text': 'weight gain', 'type': 'Disease', 'start': 1618, 'end': 1629, 'mesh': 'D015430'}, {'text': 'somnolence', 'type': 'Disease', 'start': 1752, 'end': 1762, 'mesh': 'D006970'}, {'text': 'Olanzapine', 'type': 'Chemical', 'start': 1825, 'end': 1835, 'mesh': 'C076029'}, {'text': 'bipolar mania', 'type': 'Disease', 'start': 1905, 'end': 1918, 'mesh': 'D001714'}]"
+1339,11026989,The effect of pupil dilation with tropicamide on vision and driving simulator performance.,"PURPOSE: To assess the effect of pupil dilation on vision and driving ability. METHODS: A series of tests on various parameters of visual function and driving simulator performance were performed on 12 healthy drivers, before and after pupil dilation using guttae tropicamide 1%. A driving simulator (Transport Research Laboratory) was used to measure reaction time (RT), speed maintenance and steering accuracy. Tests of basic visual function included high- and low-contrast visual acuity (HCVA and LCVA), Pelli-Robson contrast threshold (CT) and Goldmann perimetry (FIELDS). Useful Field of View (UFOV--a test of visual attention) was also undertaken. The mean differences in the pre- and post-dilatation measurements were tested for statistical significance at the 95% level using one-tail paired t-tests. RESULTS: Pupillary dilation resulted in a statistically significant deterioration in CT and HCVA only. Five of 12 drivers also exhibited deterioration in LCVA, CT and RT. Little evidence emerged for deterioration in FIELDS and UFOV. Also, 7 of 12 drivers appeared to adjust their driving behaviour by reducing their speed on the driving simulator, leading to improved steering accuracy. CONCLUSIONS: Pupillary dilation may lead to a decrease in vision and daylight driving performance in young people. A larger study, including a broader spectrum of subjects, is warranted before guidelines can be recommended.","[{'text': 'pupil dilation', 'type': 'Disease', 'start': 14, 'end': 28, 'mesh': 'D015878'}, {'text': 'tropicamide', 'type': 'Chemical', 'start': 34, 'end': 45, 'mesh': 'D014331'}, {'text': 'pupil dilation', 'type': 'Disease', 'start': 124, 'end': 138, 'mesh': 'D015878'}, {'text': 'pupil dilation', 'type': 'Disease', 'start': 327, 'end': 341, 'mesh': 'D015878'}, {'text': 'tropicamide', 'type': 'Chemical', 'start': 355, 'end': 366, 'mesh': 'D014331'}, {'text': 'Pupillary dilation', 'type': 'Disease', 'start': 909, 'end': 927, 'mesh': 'D015878'}, {'text': 'Pupillary dilation', 'type': 'Disease', 'start': 1300, 'end': 1318, 'mesh': 'D015878'}]"
+1340,11105626,A case of isotretinoin embryopathy with bilateral anotia and Taussig-Bing malformation.,We report a newborn infant with multiple congenital anomalies (anotia and Taussig-Bing malformation) due to exposure to isotretinoin within the first trimester. In this paper we aim to draw to the fact that caution is needed when prescribing vitamin A-containing drugs to women of childbearing years.,"[{'text': 'isotretinoin embryopathy', 'type': 'Disease', 'start': 10, 'end': 34, 'mesh': 'C535670'}, {'text': 'anotia', 'type': 'Disease', 'start': 50, 'end': 56, 'mesh': 'D065817'}, {'text': 'Taussig-Bing malformation', 'type': 'Disease', 'start': 61, 'end': 86, 'mesh': 'D004310'}, {'text': 'anotia', 'type': 'Disease', 'start': 151, 'end': 157, 'mesh': 'D065817'}, {'text': 'Taussig-Bing malformation', 'type': 'Disease', 'start': 162, 'end': 187, 'mesh': 'D004310'}, {'text': 'isotretinoin', 'type': 'Chemical', 'start': 208, 'end': 220, 'mesh': 'D015474'}, {'text': 'vitamin A', 'type': 'Chemical', 'start': 330, 'end': 339, 'mesh': 'D014801'}]"
+1341,11135381,"Effect of methoxamine on maximum urethral pressure in women with genuine stress incontinence: a placebo-controlled, double-blind crossover study.","The aim of the study was to evaluate the potential role for a selective alpha1-adrenoceptor agonist in the treatment of urinary stress incontinence. A randomised, double-blind, placebo-controlled, crossover study design was employed. Half log incremental doses of intravenous methoxamine or placebo (saline) were administered to a group of women with genuine stress incontinence while measuring maximum urethral pressure (MUP), blood pressure, heart rate, and symptomatic side effects. Methoxamine evoked non-significant increases in MUP and diastolic blood pressure but caused a significant rise in systolic blood pressure and significant fall in heart rate at maximum dosage. Systemic side effects including piloerection, headache, and cold extremities were experienced in all subjects. The results indicate that the clinical usefulness of direct, peripherally acting sub-type-selective alpha1-adrenoceptor agonists in the medical treatment of stress incontinence may be limited by associated piloerection and cardiovascular side effects.","[{'text': 'methoxamine', 'type': 'Chemical', 'start': 10, 'end': 21, 'mesh': 'D008729'}, {'text': 'stress incontinence', 'type': 'Disease', 'start': 73, 'end': 92, 'mesh': 'D014550'}, {'text': 'urinary stress incontinence', 'type': 'Disease', 'start': 266, 'end': 293, 'mesh': 'D014550'}, {'text': 'methoxamine', 'type': 'Chemical', 'start': 422, 'end': 433, 'mesh': 'D008729'}, {'text': 'stress incontinence', 'type': 'Disease', 'start': 505, 'end': 524, 'mesh': 'D014550'}, {'text': 'Methoxamine', 'type': 'Chemical', 'start': 632, 'end': 643, 'mesh': 'D008729'}, {'text': 'a significant rise in systolic blood pressure', 'type': 'Disease', 'start': 724, 'end': 769, 'mesh': 'D006973'}, {'text': 'headache', 'type': 'Disease', 'start': 870, 'end': 878, 'mesh': 'D006261'}, {'text': 'stress incontinence', 'type': 'Disease', 'start': 1092, 'end': 1111, 'mesh': 'D014550'}]"
+1342,11176729,Toleration of high doses of angiotensin-converting enzyme inhibitors in patients with chronic heart failure: results from the ATLAS trial. The Assessment of Treatment with Lisinopril and Survival.,"BACKGROUND: Treatment with angiotensin-converting enzyme (ACE) inhibitors reduces mortality and morbidity in patients with chronic heart failure (CHF), but most affected patients are not receiving these agents or are being treated with doses lower than those found to be efficacious in trials, primarily because of concerns about the safety and tolerability of these agents, especially at the recommended doses. The present study examines the safety and tolerability of high- compared with low-dose lisinopril in CHF. METHODS: The Assessment of Lisinopril and Survival study was a multicenter, randomized, double-blind trial in which patients with or without previous ACE inhibitor treatment were stabilized receiving medium-dose lisinopril (12.5 or 15.0 mg once daily [OD]) for 2 to 4 weeks and then randomized to high- (35.0 or 32.5 mg OD) or low-dose (5.0 or 2.5 mg OD) groups. Patients with New York Heart Association classes II to IV CHF and left ventricular ejection fractions of no greater than 0.30 (n = 3164) were randomized and followed up for a median of 46 months. We examined the occurrence of adverse events and the need for discontinuation and dose reduction during treatment, with a focus on hypotension and renal dysfunction. RESULTS: Of 405 patients not previously receiving an ACE inhibitor, doses in only 4.2% could not be titrated to the medium doses required for randomization because of symptoms possibly related to hypotension (2.0%) or because of renal dysfunction or hyperkalemia (2.3%). Doses in more than 90% of randomized patients in the high- and low-dose groups were titrated to their assigned target, and the mean doses of blinded medication in both groups remained similar throughout the study. Withdrawals occurred in 27.1% of the high- and 30.7% of the low-dose groups. Subgroups presumed to be at higher risk for ACE inhibitor intolerance (blood pressure, <120 mm Hg; creatinine, > or =132.6 micromol/L [> or =1.5 mg/dL]; age, > or =70 years; and patients with diabetes) generally tolerated the high-dose strategy. CONCLUSIONS: These findings demonstrate that ACE inhibitor therapy in most patients with CHF can be successfully titrated to and maintained at high doses, and that more aggressive use of these agents is warranted.","[{'text': 'angiotensin-converting enzyme inhibitors', 'type': 'Chemical', 'start': 28, 'end': 68, 'mesh': 'D000806'}, {'text': 'heart failure', 'type': 'Disease', 'start': 94, 'end': 107, 'mesh': 'D006333'}, {'text': 'Lisinopril', 'type': 'Chemical', 'start': 172, 'end': 182, 'mesh': 'D017706'}, {'text': 'angiotensin-converting enzyme (ACE) inhibitors', 'type': 'Chemical', 'start': 224, 'end': 270, 'mesh': 'D000806'}, {'text': 'heart failure', 'type': 'Disease', 'start': 328, 'end': 341, 'mesh': 'D006333'}, {'text': 'CHF', 'type': 'Disease', 'start': 343, 'end': 346, 'mesh': 'D006333'}, {'text': 'lisinopril', 'type': 'Chemical', 'start': 696, 'end': 706, 'mesh': 'D017706'}, {'text': 'CHF', 'type': 'Disease', 'start': 710, 'end': 713, 'mesh': 'D006333'}, {'text': 'Lisinopril', 'type': 'Chemical', 'start': 742, 'end': 752, 'mesh': 'D017706'}, {'text': 'ACE inhibitor', 'type': 'Chemical', 'start': 865, 'end': 878, 'mesh': 'D000806'}, {'text': 'lisinopril', 'type': 'Chemical', 'start': 927, 'end': 937, 'mesh': 'D017706'}, {'text': 'CHF', 'type': 'Disease', 'start': 1136, 'end': 1139, 'mesh': 'D006333'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1405, 'end': 1416, 'mesh': 'D007022'}, {'text': 'renal dysfunction', 'type': 'Disease', 'start': 1421, 'end': 1438, 'mesh': 'D007674'}, {'text': 'ACE inhibitor', 'type': 'Chemical', 'start': 1493, 'end': 1506, 'mesh': 'D000806'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1636, 'end': 1647, 'mesh': 'D007022'}, {'text': 'renal dysfunction', 'type': 'Disease', 'start': 1669, 'end': 1686, 'mesh': 'D007674'}, {'text': 'hyperkalemia', 'type': 'Disease', 'start': 1690, 'end': 1702, 'mesh': 'D006947'}, {'text': 'ACE inhibitor', 'type': 'Chemical', 'start': 2046, 'end': 2059, 'mesh': 'D000806'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 2101, 'end': 2111, 'mesh': 'D003404'}, {'text': 'diabetes', 'type': 'Disease', 'start': 2194, 'end': 2202, 'mesh': 'D003920'}, {'text': 'ACE inhibitor', 'type': 'Chemical', 'start': 2293, 'end': 2306, 'mesh': 'D000806'}, {'text': 'CHF', 'type': 'Disease', 'start': 2337, 'end': 2340, 'mesh': 'D006333'}]"
+1343,11229942,"Cocaine, ethanol, and cocaethylene cardiotoxity in an animal model of cocaine and ethanol abuse.","OBJECTIVES: Simultaneous abuse of cocaine and ethanol affects 12 million Americans annually. In combination, these substances are substantially more toxic than either drug alone. Their combined cardiac toxicity may be due to independent effects of each drug; however, they may also be due to cocaethylene (CE), a cocaine metabolite formed only in the presence of ethanol. The purpose of this study was to delineate the role of CE in the combined cardiotoxicity of cocaine and ethanol in a model simulating their abuse. METHODS: Twenty-three dogs were randomized to receive either 1) three intravenous (IV) boluses of cocaine 7.5 mg/kg with ethanol (1 g/kg) as an IV infusion (C+E, n = 8), 2) three cocaine boluses only (C, n = 6), 3) ethanol infusion only (E, n = 5), or 4) placebo boluses and infusion (n = 4). Hemodynamic measurements, electrocardiograms, and serum drug concentrations were obtained at baseline, and then at fixed time intervals after each drug was administered. RESULTS: Two of eight dogs in the C+E group experienced cardiovascular collapse. The most dramatic hemodynamic changes occurred after each cocaine bolus in the C+E and C only groups; however, persistent hemodynamic changes occurred in the C+E group. Peak CE levels were associated with a 45% (SD +/- 22%, 95% CI = 22% to 69%) decrease in cardiac output (p < 0.05), a 56% (SD +/- 23%, 95% CI = 32% to 80%) decrease in dP/dt(max) (p <.006), and a 23% (SD +/- 15%, 95% CI = 7% to 49%) decrease in SVO(2) (p < 0.025). Ventricular arrhythmias were primarily observed in the C+E group, in which four of eight dogs experienced ventricular tachycardia. CONCLUSIONS: Cocaine and ethanol in combination were more toxic than either substance alone. Co-administration resulted in prolonged cardiac toxicity and was dysrhythmogenic. Peak serum cocaethylene concentrations were associated with prolonged myocardial depression.","[{'text': 'Cocaine', 'type': 'Chemical', 'start': 0, 'end': 7, 'mesh': 'D003042'}, {'text': 'ethanol', 'type': 'Chemical', 'start': 9, 'end': 16, 'mesh': 'D000431'}, {'text': 'cocaethylene', 'type': 'Chemical', 'start': 22, 'end': 34, 'mesh': 'C066444'}, {'text': 'cardiotoxity', 'type': 'Disease', 'start': 35, 'end': 47, 'mesh': 'D066126'}, {'text': 'cardiac toxicity', 'type': 'Disease', 'start': 291, 'end': 307, 'mesh': 'D066126'}, {'text': 'cocaethylene', 'type': 'Chemical', 'start': 389, 'end': 401, 'mesh': 'C066444'}, {'text': 'CE', 'type': 'Chemical', 'start': 403, 'end': 405, 'mesh': 'C066444'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 410, 'end': 417, 'mesh': 'D003042'}, {'text': 'ethanol', 'type': 'Chemical', 'start': 460, 'end': 467, 'mesh': 'D000431'}, {'text': 'CE', 'type': 'Chemical', 'start': 524, 'end': 526, 'mesh': 'C066444'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 543, 'end': 557, 'mesh': 'D066126'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 561, 'end': 568, 'mesh': 'D003042'}, {'text': 'ethanol', 'type': 'Chemical', 'start': 573, 'end': 580, 'mesh': 'D000431'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 714, 'end': 721, 'mesh': 'D003042'}, {'text': 'ethanol', 'type': 'Chemical', 'start': 737, 'end': 744, 'mesh': 'D000431'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 795, 'end': 802, 'mesh': 'D003042'}, {'text': 'ethanol', 'type': 'Chemical', 'start': 831, 'end': 838, 'mesh': 'D000431'}, {'text': 'cardiovascular collapse', 'type': 'Disease', 'start': 1135, 'end': 1158, 'mesh': '-1'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1218, 'end': 1225, 'mesh': 'D003042'}, {'text': 'CE', 'type': 'Chemical', 'start': 1334, 'end': 1336, 'mesh': 'C066444'}, {'text': 'decrease in cardiac output', 'type': 'Disease', 'start': 1405, 'end': 1431, 'mesh': 'D002303'}, {'text': 'Ventricular arrhythmias', 'type': 'Disease', 'start': 1593, 'end': 1616, 'mesh': 'D001145'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 1699, 'end': 1722, 'mesh': 'D017180'}, {'text': 'Cocaine', 'type': 'Chemical', 'start': 1737, 'end': 1744, 'mesh': 'D003042'}, {'text': 'ethanol', 'type': 'Chemical', 'start': 1749, 'end': 1756, 'mesh': 'D000431'}, {'text': 'cardiac toxicity', 'type': 'Disease', 'start': 1857, 'end': 1873, 'mesh': 'D066126'}, {'text': 'cocaethylene', 'type': 'Chemical', 'start': 1910, 'end': 1922, 'mesh': 'C066444'}, {'text': 'myocardial depression', 'type': 'Disease', 'start': 1969, 'end': 1990, 'mesh': 'D009202'}]"
+1344,11299446,Worsening of Parkinsonism after the use of veralipride for treatment of menopause: case report.,"We describe a female patient with stable Parkinson's disease who has shown a marked worsening of her motor functions following therapy of menopause related symptoms with veralipride, as well as the improvement of her symptoms back to baseline after discontinuation of the drug. We emphasize the anti-dopaminergic effect of veralipride.","[{'text': 'Parkinsonism', 'type': 'Disease', 'start': 13, 'end': 25, 'mesh': 'D010302'}, {'text': 'veralipride', 'type': 'Chemical', 'start': 43, 'end': 54, 'mesh': 'C027429'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 137, 'end': 156, 'mesh': 'D010302'}, {'text': 'veralipride', 'type': 'Chemical', 'start': 266, 'end': 277, 'mesh': 'C027429'}, {'text': 'veralipride', 'type': 'Chemical', 'start': 419, 'end': 430, 'mesh': 'C027429'}]"
+1345,11366874,Viracept and irregular heartbeat warning.,"A group of doctors in Boston warn that the protease inhibitor Viracept may cause an irregular heart beat, known as bradycardia, in people with HIV. Bradycardia occurred in a 45-year-old male patient who was Viracept in combination with other anti-HIV drugs. The symptoms ceased after switching to another drug combination.","[{'text': 'Viracept', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D019888'}, {'text': 'irregular heartbeat', 'type': 'Disease', 'start': 13, 'end': 32, 'mesh': 'D001145'}, {'text': 'Viracept', 'type': 'Chemical', 'start': 104, 'end': 112, 'mesh': 'D019888'}, {'text': 'irregular heart beat', 'type': 'Disease', 'start': 126, 'end': 146, 'mesh': 'D001145'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 157, 'end': 168, 'mesh': 'D001919'}, {'text': 'Bradycardia', 'type': 'Disease', 'start': 190, 'end': 201, 'mesh': 'D001919'}, {'text': 'Viracept', 'type': 'Chemical', 'start': 249, 'end': 257, 'mesh': 'D019888'}]"
+1346,11380496,Frequency of appearance of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) in Graves' disease patients treated with propylthiouracil and the relationship between MPO-ANCA and clinical manifestations.,"OBJECTIVE: Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-positive vasculitis has been reported in patients with Graves' disease who were treated with propylthiouracil (PTU). The appearance of MPO-ANCA in these cases was suspected of being related to PTU because the titres of MPO-ANCA decreased when PTU was stopped. Nevertheless, there have been no studies on the temporal relationship between the appearance of MPO-ANCA and vasculitis during PTU therapy, or on the incidence of MPO-ANCA in untreated Graves' disease patients. Therefore, we sought to address these parameters in patients with Graves' disease. PATIENTS: We investigated 102 untreated patients with hyperthyroidism due to Graves' disease for the presence of MPO-ANCA, and for the development vasculitis after starting PTU therapy. Twenty-nine of them were later excluded because of adverse effects of PTU or because the observation period was less than 3 months. The remaining 73 patients (55 women and 18 men), all of whom were examined for more than 3 months, were adopted as the subjects of the investigation. The median observation period was 23.6 months (range: 3-37 months). MEASUREMENTS: MPO-ANCA was measured at intervals of 2-6 months. RESULTS: Before treatment, the MPO-ANCA titres of all 102 untreated Graves' disease patients were within the reference range (below 10 U/ml). Three (4.1%) of the 73 patients were positive for MPO-ANCA at 13, 16 and 17 months, respectively, after the start of PTU therapy. In two of them, the MPO-ANCA titres transiently increased to 12.8 and 15.0 U/ml, respectively, despite continued PTU therapy, but no vasculitic disorders developed. In the third patient, the MPO-ANCA titre increased to 204 U/ml and she developed a higher fever, oral ulcers and polyarthralgia, but the symptoms resolved 2 weeks after stopping PTU therapy, and the MPO-ANCA titre decreased to 20.7 U/ml by 4 months after discontinuing PTU. CONCLUSIONS: PTU therapy may be related to the appearance of MPO-ANCA, but MPO-ANCA does not appear to be closely related to vasculitis.","[{'text': ""Graves' disease"", 'type': 'Disease', 'start': 93, 'end': 108, 'mesh': 'D006111'}, {'text': 'propylthiouracil', 'type': 'Chemical', 'start': 131, 'end': 147, 'mesh': 'D011441'}, {'text': 'vasculitis', 'type': 'Disease', 'start': 298, 'end': 308, 'mesh': 'D014657'}, {'text': ""Graves' disease"", 'type': 'Disease', 'start': 344, 'end': 359, 'mesh': 'D006111'}, {'text': 'propylthiouracil', 'type': 'Chemical', 'start': 382, 'end': 398, 'mesh': 'D011441'}, {'text': 'PTU', 'type': 'Chemical', 'start': 400, 'end': 403, 'mesh': 'D011441'}, {'text': 'PTU', 'type': 'Chemical', 'start': 482, 'end': 485, 'mesh': 'D011441'}, {'text': 'PTU', 'type': 'Chemical', 'start': 532, 'end': 535, 'mesh': 'D011441'}, {'text': 'vasculitis', 'type': 'Disease', 'start': 658, 'end': 668, 'mesh': 'D014657'}, {'text': 'PTU', 'type': 'Chemical', 'start': 676, 'end': 679, 'mesh': 'D011441'}, {'text': ""Graves' disease"", 'type': 'Disease', 'start': 734, 'end': 749, 'mesh': 'D006111'}, {'text': ""Graves' disease"", 'type': 'Disease', 'start': 826, 'end': 841, 'mesh': 'D006111'}, {'text': 'hyperthyroidism', 'type': 'Disease', 'start': 897, 'end': 912, 'mesh': 'D006980'}, {'text': ""Graves' disease"", 'type': 'Disease', 'start': 920, 'end': 935, 'mesh': 'D006111'}, {'text': 'vasculitis', 'type': 'Disease', 'start': 990, 'end': 1000, 'mesh': 'D014657'}, {'text': 'PTU', 'type': 'Chemical', 'start': 1016, 'end': 1019, 'mesh': 'D011441'}, {'text': 'PTU', 'type': 'Chemical', 'start': 1099, 'end': 1102, 'mesh': 'D011441'}, {'text': ""Graves' disease"", 'type': 'Disease', 'start': 1511, 'end': 1526, 'mesh': 'D006111'}, {'text': 'PTU', 'type': 'Chemical', 'start': 1702, 'end': 1705, 'mesh': 'D011441'}, {'text': 'PTU', 'type': 'Chemical', 'start': 1828, 'end': 1831, 'mesh': 'D011441'}, {'text': 'vasculitic disorders', 'type': 'Disease', 'start': 1848, 'end': 1868, 'mesh': 'D014652'}, {'text': 'fever', 'type': 'Disease', 'start': 1970, 'end': 1975, 'mesh': 'D005334'}, {'text': 'oral ulcers', 'type': 'Disease', 'start': 1977, 'end': 1988, 'mesh': 'D019226'}, {'text': 'polyarthralgia', 'type': 'Disease', 'start': 1993, 'end': 2007, 'mesh': 'D018771'}, {'text': 'PTU', 'type': 'Chemical', 'start': 2058, 'end': 2061, 'mesh': 'D011441'}, {'text': 'PTU', 'type': 'Chemical', 'start': 2149, 'end': 2152, 'mesh': 'D011441'}, {'text': 'PTU', 'type': 'Chemical', 'start': 2167, 'end': 2170, 'mesh': 'D011441'}, {'text': 'vasculitis', 'type': 'Disease', 'start': 2279, 'end': 2289, 'mesh': 'D014657'}]"
+1347,11385188,Prevalence of heart disease in asymptomatic chronic cocaine users.,"To determine the prevalence of heart disease in outpatient young asymptomatic chronic cocaine users, 35 cocaine users and 32 age-matched controls underwent resting and exercise electrocardiography (ECG) and Doppler echocardiography. Findings consistent with coronary artery disease were detected in 12 (34%) patients and 3 (9%) controls (p = 0.01). Decreased left ventricular systolic function was demonstrated in 5 (14%) patients, but in none of the controls (p = 0.055). Finally, resting and peak exercise abnormal left ventricular filling was detected in 38 and 35% of patients as compared to 19 and 9% of controls, respectively (p = 0.11 and 0.02, respectively). We conclude that coronary artery or myocardial disease is common (38%) in young asymptomatic chronic cocaine users. Therefore, screening ECG and echocardiography may be warranted in these patients.","[{'text': 'heart disease', 'type': 'Disease', 'start': 14, 'end': 27, 'mesh': 'D006331'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 52, 'end': 59, 'mesh': 'D003042'}, {'text': 'heart disease', 'type': 'Disease', 'start': 98, 'end': 111, 'mesh': 'D006331'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 153, 'end': 160, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 171, 'end': 178, 'mesh': 'D003042'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 325, 'end': 348, 'mesh': 'D003324'}, {'text': 'abnormal left ventricular filling', 'type': 'Disease', 'start': 575, 'end': 608, 'mesh': 'D018487'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 835, 'end': 842, 'mesh': 'D003042'}]"
+1348,11395263,Cardioprotective effects of Picrorrhiza kurroa against isoproterenol-induced myocardial stress in rats.,The cardioprotective effect of the ethanol extract of Picrorrhiza kurroa rhizomes and roots (PK) on isoproterenol-induced myocardial infarction in rats with respect to lipid metabolism in serum and heart tissue has been investigated. Oral pre-treatment with PK (80 mg kg(-1) day(-1) for 15 days) significantly prevented the isoproterenol-induced myocardial infarction and maintained the rats at near normal status.,"[{'text': 'isoproterenol', 'type': 'Chemical', 'start': 55, 'end': 68, 'mesh': 'D007545'}, {'text': 'ethanol', 'type': 'Chemical', 'start': 139, 'end': 146, 'mesh': 'D000431'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 204, 'end': 217, 'mesh': 'D007545'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 226, 'end': 247, 'mesh': 'D009203'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 428, 'end': 441, 'mesh': 'D007545'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 450, 'end': 471, 'mesh': 'D009203'}]"
+1349,11401944,Phase 2 early afterdepolarization as a trigger of polymorphic ventricular tachycardia in acquired long-QT syndrome : direct evidence from intracellular recordings in the intact left ventricular wall.,"BACKGROUND: This study examined the role of phase 2 early afterdepolarization (EAD) in producing a trigger to initiate torsade de pointes (TdP) with QT prolongation induced by dl-sotalol and azimilide. The contribution of transmural dispersion of repolarization (TDR) to transmural propagation of EAD and the maintenance of TdP was also evaluated. METHODS AND RESULTS: Transmembrane action potentials from epicardium, midmyocardium, and endocardium were recorded simultaneously, together with a transmural ECG, in arterially perfused canine and rabbit left ventricular preparations. dl-Sotalol preferentially prolonged action potential duration (APD) in M cells dose-dependently (1 to 100 micromol/L), leading to QT prolongation and an increase in TDR. Azimilide, however, significantly prolonged APD and QT interval at concentrations from 0.1 to 10 micromol/L but shortened them at 30 micromol/L. Unlike dl-sotalol, azimilide (>3 micromol/L) increased epicardial APD markedly, causing a diminished TDR. Although both dl-sotalol and azimilide rarely induced EADs in canine left ventricles, they produced frequent EADs in rabbits, in which more pronounced QT prolongation was seen. An increase in TDR by dl-sotalol facilitated transmural propagation of EADs that initiated multiple episodes of spontaneous TdP in 3 of 6 rabbit left ventricles. Of note, although azimilide (3 to 10 micromol/L) increased APD more than dl-sotalol, its EADs often failed to propagate transmurally, probably because of a diminished TDR. CONCLUSIONS: This study provides the first direct evidence from intracellular action potential recordings that phase 2 EAD can be generated from intact ventricular wall and produce a trigger to initiate the onset of TdP under QT prolongation.","[{'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 62, 'end': 85, 'mesh': 'D017180'}, {'text': 'long-QT syndrome', 'type': 'Disease', 'start': 98, 'end': 114, 'mesh': 'D008133'}, {'text': 'torsade de pointes', 'type': 'Disease', 'start': 319, 'end': 337, 'mesh': 'D016171'}, {'text': 'TdP', 'type': 'Disease', 'start': 339, 'end': 342, 'mesh': 'D016171'}, {'text': 'QT prolongation', 'type': 'Disease', 'start': 349, 'end': 364, 'mesh': 'D008133'}, {'text': 'sotalol', 'type': 'Chemical', 'start': 379, 'end': 386, 'mesh': 'D013015'}, {'text': 'azimilide', 'type': 'Chemical', 'start': 391, 'end': 400, 'mesh': 'C086123'}, {'text': 'TdP', 'type': 'Disease', 'start': 524, 'end': 527, 'mesh': 'D016171'}, {'text': 'Sotalol', 'type': 'Chemical', 'start': 786, 'end': 793, 'mesh': 'D013015'}, {'text': 'QT prolongation', 'type': 'Disease', 'start': 913, 'end': 928, 'mesh': 'D008133'}, {'text': 'Azimilide', 'type': 'Chemical', 'start': 953, 'end': 962, 'mesh': 'C086123'}, {'text': 'sotalol', 'type': 'Chemical', 'start': 1108, 'end': 1115, 'mesh': 'D013015'}, {'text': 'azimilide', 'type': 'Chemical', 'start': 1117, 'end': 1126, 'mesh': 'C086123'}, {'text': 'sotalol', 'type': 'Chemical', 'start': 1221, 'end': 1228, 'mesh': 'D013015'}, {'text': 'azimilide', 'type': 'Chemical', 'start': 1233, 'end': 1242, 'mesh': 'C086123'}, {'text': 'QT prolongation', 'type': 'Disease', 'start': 1355, 'end': 1370, 'mesh': 'D008133'}, {'text': 'sotalol', 'type': 'Chemical', 'start': 1406, 'end': 1413, 'mesh': 'D013015'}, {'text': 'TdP', 'type': 'Disease', 'start': 1505, 'end': 1508, 'mesh': 'D016171'}, {'text': 'azimilide', 'type': 'Chemical', 'start': 1561, 'end': 1570, 'mesh': 'C086123'}, {'text': 'sotalol', 'type': 'Chemical', 'start': 1619, 'end': 1626, 'mesh': 'D013015'}, {'text': 'TdP', 'type': 'Disease', 'start': 1931, 'end': 1934, 'mesh': 'D016171'}, {'text': 'QT prolongation', 'type': 'Disease', 'start': 1941, 'end': 1956, 'mesh': 'D008133'}]"
+1350,11425091,Prenatal cocaine exposure and cranial sonographic findings in preterm infants.,PURPOSE: Prenatal cocaine exposure has been linked with subependymal hemorrhage and the formation of cysts that are detectable on cranial sonography in neonates born at term. We sought to determine if prenatal cocaine exposure increases the incidence of subependymal cysts in preterm infants. METHODS: We retrospectively reviewed the medical records and cranial sonograms obtained during a 1-year period on 122 premature (< 36 weeks of gestation) infants. Infants were categorized into 1 of 2 groups: those exposed to cocaine and those not exposed to cocaine. Infants were assigned to the cocaine-exposed group if there was a maternal history of cocaine abuse during pregnancy or if maternal or neonatal urine toxicology results were positive at the time of delivery. RESULTS: Five of the 122 infants were excluded from the study because of insufficient medical and drug histories. The incidence of subependymal cysts in the 117 remaining infants was 14% (16 of 117). The incidence of subependymal cysts in infants exposed to cocaine prenatally was 44% (8 of 18) compared with 8% (8 of 99) in the unexposed group (p < 0.01). CONCLUSIONS: We found an increased incidence of subependymal cyst formation in preterm infants who were exposed to cocaine prenatally. This result is consistent with results of similar studies in term infants.,"[{'text': 'cocaine', 'type': 'Chemical', 'start': 9, 'end': 16, 'mesh': 'D003042'}, {'text': 'preterm infants', 'type': 'Disease', 'start': 62, 'end': 77, 'mesh': 'D007235'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 97, 'end': 104, 'mesh': 'D003042'}, {'text': 'hemorrhage', 'type': 'Disease', 'start': 148, 'end': 158, 'mesh': 'D006470'}, {'text': 'cysts', 'type': 'Disease', 'start': 180, 'end': 185, 'mesh': 'D003560'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 289, 'end': 296, 'mesh': 'D003042'}, {'text': 'preterm infants', 'type': 'Disease', 'start': 355, 'end': 370, 'mesh': 'D007235'}, {'text': 'premature (< 36 weeks of gestation) infants', 'type': 'Disease', 'start': 490, 'end': 533, 'mesh': 'D007235'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 597, 'end': 604, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 630, 'end': 637, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 668, 'end': 675, 'mesh': 'D003042'}, {'text': 'cocaine abuse', 'type': 'Disease', 'start': 725, 'end': 738, 'mesh': 'D019970'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1105, 'end': 1112, 'mesh': 'D003042'}, {'text': 'preterm infants', 'type': 'Disease', 'start': 1283, 'end': 1298, 'mesh': 'D007235'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1319, 'end': 1326, 'mesh': 'D003042'}]"
+1351,11439380,Thalidomide neuropathy in patients treated for metastatic prostate cancer.,"We prospectively evaluated thalidomide-induced neuropathy using electrodiagnostic studies. Sixty-seven men with metastatic androgen-independent prostate cancer in an open-label trial of oral thalidomide underwent neurologic examinations and nerve conduction studies (NCS) prior to and at 3-month intervals during treatment. NCS included recording of sensory nerve action potentials (SNAPs) from median, radial, ulnar, and sural nerves. SNAP amplitudes for each nerve were expressed as the percentage of its baseline, and the mean of the four was termed the SNAP index. A 40% decline in the SNAP index was considered clinically significant. Thalidomide was discontinued in 55 patients for lack of therapeutic response. Of 67 patients initially enrolled, 24 remained on thalidomide for 3 months, 8 remained at 6 months, and 3 remained at 9 months. Six patients developed neuropathy. Clinical symptoms and a decline in the SNAP index occurred concurrently. Older age and cumulative dose were possible contributing factors. Neuropathy may thus be a common complication of thalidomide in older patients. The SNAP index can be used to monitor peripheral neuropathy, but not for early detection.","[{'text': 'Thalidomide', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D013792'}, {'text': 'neuropathy', 'type': 'Disease', 'start': 12, 'end': 22, 'mesh': 'D009422'}, {'text': 'prostate cancer', 'type': 'Disease', 'start': 58, 'end': 73, 'mesh': 'D011471'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 102, 'end': 113, 'mesh': 'D013792'}, {'text': 'neuropathy', 'type': 'Disease', 'start': 122, 'end': 132, 'mesh': 'D009422'}, {'text': 'androgen', 'type': 'Chemical', 'start': 198, 'end': 206, 'mesh': 'D000728'}, {'text': 'prostate cancer', 'type': 'Disease', 'start': 219, 'end': 234, 'mesh': 'D011471'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 266, 'end': 277, 'mesh': 'D013792'}, {'text': 'Thalidomide', 'type': 'Chemical', 'start': 715, 'end': 726, 'mesh': 'D013792'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 843, 'end': 854, 'mesh': 'D013792'}, {'text': 'neuropathy', 'type': 'Disease', 'start': 944, 'end': 954, 'mesh': 'D009422'}, {'text': 'Neuropathy', 'type': 'Disease', 'start': 1095, 'end': 1105, 'mesh': 'D009422'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 1143, 'end': 1154, 'mesh': 'D013792'}, {'text': 'peripheral neuropathy', 'type': 'Disease', 'start': 1212, 'end': 1233, 'mesh': 'D010523'}]"
+1352,11474137,Overexpression of copper/zinc-superoxide dismutase protects from kanamycin-induced hearing loss.,"The participation of reactive oxygen species in aminoglycoside-induced ototoxicity has been deduced from observations that aminoglycoside-iron complexes catalyze the formation of superoxide radicals in vitro and that antioxidants attenuate ototoxicity in vivo. We therefore hypothesized that overexpression of Cu/Zn-superoxide dismutase (h-SOD1) should protect transgenic mice from ototoxicity. Immunocytochemistry confirmed expression of h-SOD1 in inner ear tissues of transgenic C57BL/6-TgN[SOD1]3Cje mice. Transgenic and nontransgenic littermates received kanamycin (400 mg/kg body weight/day) for 10 days beginning on day 10 after birth. Auditory thresholds were tested by evoked auditory brain stem responses at 1 month after birth. In nontransgenic animals, the threshold in the kanamycin-treated group was 45-50 dB higher than in saline-injected controls. In the transgenic group, kanamycin increased the threshold by only 15 dB over the respective controls. The effects were similar at 12 and 24 kHz. The protection by overexpression of superoxide dismutase supports the hypothesis that oxidant stress plays a significant role in aminoglycoside-induced ototoxicity. The results also suggest transgenic animals as suitable models to investigate the underlying mechanisms and possible strategies for prevention.","[{'text': 'copper', 'type': 'Chemical', 'start': 18, 'end': 24, 'mesh': 'D003300'}, {'text': 'zinc', 'type': 'Chemical', 'start': 25, 'end': 29, 'mesh': 'D015032'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 30, 'end': 40, 'mesh': 'D013481'}, {'text': 'kanamycin', 'type': 'Chemical', 'start': 65, 'end': 74, 'mesh': 'D007612'}, {'text': 'hearing loss', 'type': 'Disease', 'start': 83, 'end': 95, 'mesh': 'D034381'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 127, 'end': 133, 'mesh': 'D010100'}, {'text': 'aminoglycoside', 'type': 'Chemical', 'start': 145, 'end': 159, 'mesh': 'D000617'}, {'text': 'ototoxicity', 'type': 'Disease', 'start': 168, 'end': 179, 'mesh': 'D006311'}, {'text': 'aminoglycoside', 'type': 'Chemical', 'start': 220, 'end': 234, 'mesh': 'D000617'}, {'text': 'iron', 'type': 'Chemical', 'start': 235, 'end': 239, 'mesh': 'D007501'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 276, 'end': 286, 'mesh': 'D013481'}, {'text': 'ototoxicity', 'type': 'Disease', 'start': 337, 'end': 348, 'mesh': 'D006311'}, {'text': 'Cu', 'type': 'Chemical', 'start': 407, 'end': 409, 'mesh': 'D003300'}, {'text': 'Zn', 'type': 'Chemical', 'start': 410, 'end': 412, 'mesh': 'D015032'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 413, 'end': 423, 'mesh': 'D013481'}, {'text': 'ototoxicity', 'type': 'Disease', 'start': 479, 'end': 490, 'mesh': 'D006311'}, {'text': 'kanamycin', 'type': 'Chemical', 'start': 656, 'end': 665, 'mesh': 'D007612'}, {'text': 'kanamycin', 'type': 'Chemical', 'start': 882, 'end': 891, 'mesh': 'D007612'}, {'text': 'kanamycin', 'type': 'Chemical', 'start': 985, 'end': 994, 'mesh': 'D007612'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 1142, 'end': 1152, 'mesh': 'D013481'}, {'text': 'aminoglycoside', 'type': 'Chemical', 'start': 1235, 'end': 1249, 'mesh': 'D000617'}, {'text': 'ototoxicity', 'type': 'Disease', 'start': 1258, 'end': 1269, 'mesh': 'D006311'}]"
+1353,11708428,Prednisone induces anxiety and glial cerebral changes in rats.,"OBJECTIVE: To assess whether prednisone (PDN) produces anxiety and/or cerebral glial changes in rats. METHODS: Male Wistar rats were studied and 3 groups were formed (8 rats per group). The moderate-dose group received 5 mg/kg/day PDN released from a subcutaneous implant. In the high-dose group, implants containing PDN equivalent to 60 mg/kg/day were applied. In the control group implants contained no PDN. Anxiety was assessed using an open field and elevated plus-maze devices. The number of cells and cytoplasmic transformation of astrocytes and microglia cells were assessed by immunohistochemical analyses. RESULTS: Anxiety was documented in both groups of PDN treated rats compared with controls. The magnitude of transformation of the microglia assessed by the number of intersections was significantly higher in the PDN groups than in controls in the prefrontal cortex (moderate-dose, 24.1; high-dose, 23.6; controls 18.7; p < 0.01) and striatum (moderate-dose 25.6; high-dose 26.3; controls 18.9; p < 0.01), but not in hippocampus. The number of stained microglia cells was significantly higher in the PDN treated groups in the prefrontal cortex than in controls (moderate-dose, 29.1; high-dose, 28.4; control, 17.7 cells per field; p < 0.01). Stained microglia cells were significantly more numerous striatum and hippocampus in the high-dose group compared to controls. CONCLUSION: Subacute exposure to PDN induced anxiety and reactivity of microglia. The relevance of these features for patients using PDN remains to be elucidated.","[{'text': 'Prednisone', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D011241'}, {'text': 'anxiety', 'type': 'Disease', 'start': 19, 'end': 26, 'mesh': 'D001008'}, {'text': 'prednisone', 'type': 'Chemical', 'start': 92, 'end': 102, 'mesh': 'D011241'}, {'text': 'PDN', 'type': 'Chemical', 'start': 104, 'end': 107, 'mesh': 'D011241'}, {'text': 'anxiety', 'type': 'Disease', 'start': 118, 'end': 125, 'mesh': 'D001008'}, {'text': 'PDN', 'type': 'Chemical', 'start': 294, 'end': 297, 'mesh': 'D011241'}, {'text': 'PDN', 'type': 'Chemical', 'start': 380, 'end': 383, 'mesh': 'D011241'}, {'text': 'PDN', 'type': 'Chemical', 'start': 468, 'end': 471, 'mesh': 'D011241'}, {'text': 'Anxiety', 'type': 'Disease', 'start': 473, 'end': 480, 'mesh': 'D001008'}, {'text': 'Anxiety', 'type': 'Disease', 'start': 687, 'end': 694, 'mesh': 'D001008'}, {'text': 'PDN', 'type': 'Chemical', 'start': 728, 'end': 731, 'mesh': 'D011241'}, {'text': 'PDN', 'type': 'Chemical', 'start': 890, 'end': 893, 'mesh': 'D011241'}, {'text': 'PDN', 'type': 'Chemical', 'start': 1177, 'end': 1180, 'mesh': 'D011241'}, {'text': 'PDN', 'type': 'Chemical', 'start': 1479, 'end': 1482, 'mesh': 'D011241'}, {'text': 'anxiety', 'type': 'Disease', 'start': 1491, 'end': 1498, 'mesh': 'D001008'}, {'text': 'PDN', 'type': 'Chemical', 'start': 1579, 'end': 1582, 'mesh': 'D011241'}]"
+1354,11745287,Phase II study of carboplatin and liposomal doxorubicin in patients with recurrent squamous cell carcinoma of the cervix.,"BACKGROUND: The activity of the combination of carboplatin and liposomal doxorubicin was tested in a Phase II study of patients with recurrent cervical carcinoma. METHODS: The combination of carboplatin (area under the concentration curve [AUC], 5) and liposomal doxorubicin (Doxil; starting dose, 40 mg/m(2)) was administered intravenously every 28 days to 37 patients with recurrent squamous cell cervical carcinoma to determine antitumor activity and toxicity profile. RESULTS: Twenty-nine patients were assessable for response, and 35 patients were assessable for toxicity. The overall response rate was 38%, the median time to response was 10 weeks, the median duration of response was 26 weeks, and the median survival was 37 weeks. The main toxic effect was myelosuppression, with Grade 3 and 4 neutropenia in 16 patients, anemia in 12 patients, thrombocytopenia in 11 patients, and neutropenic fever in 3 patients. Four patients had five infusion-related reactions during the infusion of liposomal doxorubicin, leading to treatment discontinuation in three patients. Grade > or = 2 nonhematologic toxicity included nausea in 17 patients, emesis in 14 patients, fatigue in 9 patients, mucositis and/or stomatitis in 8 patients, constipation in 6 patients, weight loss in 5 patients, hand-foot syndrome in 2 patients, and skin reactions in 3 patients. CONCLUSIONS: The combination of carboplatin and liposomal doxorubicin has modest activity in patients with recurrent cervical carcinoma.","[{'text': 'carboplatin', 'type': 'Chemical', 'start': 18, 'end': 29, 'mesh': 'D016190'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 44, 'end': 55, 'mesh': 'D004317'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 169, 'end': 180, 'mesh': 'D016190'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 195, 'end': 206, 'mesh': 'D004317'}, {'text': 'cervical carcinoma', 'type': 'Disease', 'start': 265, 'end': 283, 'mesh': 'D002583'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 313, 'end': 324, 'mesh': 'D016190'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 385, 'end': 396, 'mesh': 'D004317'}, {'text': 'Doxil', 'type': 'Chemical', 'start': 398, 'end': 403, 'mesh': 'D004317'}, {'text': 'toxicity', 'type': 'Disease', 'start': 576, 'end': 584, 'mesh': 'D064420'}, {'text': 'toxicity', 'type': 'Disease', 'start': 690, 'end': 698, 'mesh': 'D064420'}, {'text': 'myelosuppression', 'type': 'Disease', 'start': 887, 'end': 903, 'mesh': 'D001855'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 924, 'end': 935, 'mesh': 'D009503'}, {'text': 'anemia', 'type': 'Disease', 'start': 952, 'end': 958, 'mesh': 'D000740'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 975, 'end': 991, 'mesh': 'D013921'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1128, 'end': 1139, 'mesh': 'D004317'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1227, 'end': 1235, 'mesh': 'D064420'}, {'text': 'nausea', 'type': 'Disease', 'start': 1245, 'end': 1251, 'mesh': 'D009325'}, {'text': 'emesis', 'type': 'Disease', 'start': 1268, 'end': 1274, 'mesh': 'D014839'}, {'text': 'fatigue', 'type': 'Disease', 'start': 1291, 'end': 1298, 'mesh': 'D005221'}, {'text': 'mucositis', 'type': 'Disease', 'start': 1314, 'end': 1323, 'mesh': 'D052016'}, {'text': 'stomatitis', 'type': 'Disease', 'start': 1331, 'end': 1341, 'mesh': 'D013280'}, {'text': 'constipation', 'type': 'Disease', 'start': 1357, 'end': 1369, 'mesh': 'D003248'}, {'text': 'weight loss', 'type': 'Disease', 'start': 1385, 'end': 1396, 'mesh': 'D015431'}, {'text': 'hand-foot syndrome', 'type': 'Disease', 'start': 1412, 'end': 1430, 'mesh': 'D060831'}, {'text': 'skin reactions', 'type': 'Disease', 'start': 1450, 'end': 1464, 'mesh': 'D012871'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 1512, 'end': 1523, 'mesh': 'D016190'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1538, 'end': 1549, 'mesh': 'D004317'}, {'text': 'cervical carcinoma', 'type': 'Disease', 'start': 1597, 'end': 1615, 'mesh': 'D002583'}]"
+1355,11799346,Antimicrobial-induced mania (antibiomania): a review of spontaneous reports.,"The authors reviewed reported cases of antibiotic-induced manic episodes by means of a MEDLINE and PsychLit search for reports of antibiotic-induced mania. Unpublished reports were requested from the World Health Organization (WHO) and the Food and Drug Administration (FDA). Twenty-one reports of antimicrobial-induced mania were found in the literature. There were 6 cases implicating clarithromycin, 13 implicating isoniazid, and 1 case each implicating erythromycin and amoxicillin. The WHO reported 82 cases. Of these, clarithromycin was implicated in 23 (27.6%) cases, ciprofloxacin in 12 (14.4%) cases, and ofloxacin in 10 (12%) cases. Cotrimoxazole, metronidazole, and erythromycin were involved in 15 reported manic episodes. Cases reported by the FDA showed clarithromycin and ciprofloxacin to be the most frequently associated with the development of mania. Statistical analysis of the data would not have demonstrated a significant statistical correlative risk and was therefore not undertaken. Patients have an increased risk of developing mania while being treated with antimicrobials. Although this is not a statistically significant risk, physicians must be aware of the effect and reversibility. Further research clearly is required to determine the incidence of antimicrobial-induced mania, the relative risk factors of developing an antimicrobial-induced manic episode among various demographic populations, and the incidence of patients who continue to have persistent affective disorders once the initial episode, which occurs while the patient is taking antibiotics, subsides. The authors elected to name this syndrome ""antibiomania.""","[{'text': 'mania', 'type': 'Disease', 'start': 22, 'end': 27, 'mesh': 'D001714'}, {'text': 'antibiomania', 'type': 'Disease', 'start': 29, 'end': 41, 'mesh': 'D001714'}, {'text': 'manic', 'type': 'Disease', 'start': 135, 'end': 140, 'mesh': 'D001714'}, {'text': 'mania', 'type': 'Disease', 'start': 226, 'end': 231, 'mesh': 'D001714'}, {'text': 'mania', 'type': 'Disease', 'start': 397, 'end': 402, 'mesh': 'D001714'}, {'text': 'clarithromycin', 'type': 'Chemical', 'start': 464, 'end': 478, 'mesh': 'D017291'}, {'text': 'isoniazid', 'type': 'Chemical', 'start': 495, 'end': 504, 'mesh': 'D007538'}, {'text': 'erythromycin', 'type': 'Chemical', 'start': 534, 'end': 546, 'mesh': 'D004917'}, {'text': 'amoxicillin', 'type': 'Chemical', 'start': 551, 'end': 562, 'mesh': 'D000658'}, {'text': 'clarithromycin', 'type': 'Chemical', 'start': 601, 'end': 615, 'mesh': 'D017291'}, {'text': 'ciprofloxacin', 'type': 'Chemical', 'start': 652, 'end': 665, 'mesh': 'D002939'}, {'text': 'ofloxacin', 'type': 'Chemical', 'start': 691, 'end': 700, 'mesh': 'D015242'}, {'text': 'Cotrimoxazole', 'type': 'Chemical', 'start': 720, 'end': 733, 'mesh': 'D015662'}, {'text': 'metronidazole', 'type': 'Chemical', 'start': 735, 'end': 748, 'mesh': 'D008795'}, {'text': 'erythromycin', 'type': 'Chemical', 'start': 754, 'end': 766, 'mesh': 'D004917'}, {'text': 'manic', 'type': 'Disease', 'start': 796, 'end': 801, 'mesh': 'D001714'}, {'text': 'clarithromycin', 'type': 'Chemical', 'start': 845, 'end': 859, 'mesh': 'D017291'}, {'text': 'ciprofloxacin', 'type': 'Chemical', 'start': 864, 'end': 877, 'mesh': 'D002939'}, {'text': 'mania', 'type': 'Disease', 'start': 939, 'end': 944, 'mesh': 'D001714'}, {'text': 'mania', 'type': 'Disease', 'start': 1130, 'end': 1135, 'mesh': 'D001714'}, {'text': 'mania', 'type': 'Disease', 'start': 1379, 'end': 1384, 'mesh': 'D001714'}, {'text': 'manic', 'type': 'Disease', 'start': 1451, 'end': 1456, 'mesh': 'D001714'}, {'text': 'antibiomania', 'type': 'Disease', 'start': 1719, 'end': 1731, 'mesh': 'D001714'}]"
+1356,11835460,Levodopa-induced ocular dyskinesias in Parkinson's disease.,"Levodopa-induced ocular dyskinesias are very uncommon. Usually they occur simultaneously with limb peak-dose choreatic dyskinesias. We report on a patient with leftward and upward deviations of gaze during the peak effect of levodopa, and hypothesize that a severe dopaminergic denervation in the caudate nucleus is needed for the appearance of these levodopa-induce ocular dyskinesias.","[{'text': 'Levodopa', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D007980'}, {'text': 'ocular dyskinesias', 'type': 'Disease', 'start': 17, 'end': 35, 'mesh': 'D015835'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 39, 'end': 58, 'mesh': 'D010300'}, {'text': 'Levodopa', 'type': 'Chemical', 'start': 60, 'end': 68, 'mesh': 'D007980'}, {'text': 'ocular dyskinesias', 'type': 'Disease', 'start': 77, 'end': 95, 'mesh': 'D015835'}, {'text': 'choreatic dyskinesias', 'type': 'Disease', 'start': 169, 'end': 190, 'mesh': 'D002819'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 285, 'end': 293, 'mesh': 'D007980'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 411, 'end': 419, 'mesh': 'D007980'}, {'text': 'ocular dyskinesias', 'type': 'Disease', 'start': 427, 'end': 445, 'mesh': 'D015835'}]"
+1357,11915580,"A comparison of glyceryl trinitrate with diclofenac for the treatment of primary dysmenorrhea: an open, randomized, cross-over trial.","Primary dysmenorrhea is a syndrome characterized by painful uterine contractility caused by a hypersecretion of endometrial prostaglandins; non-steroidal anti-inflammatory drugs are the first choice for its treatment. However, in vivo and in vitro studies have demonstrated that myometrial cells are also targets of the relaxant effects of nitric oxide (NO). The aim of the present study was to determine the efficacy of glyceryl trinitrate (GTN), an NO donor, in the resolution of primary dysmenorrhea in comparison with diclofenac (DCF). A total of 24 patients with the diagnosis of severe primary dysmenorrhea were studied during two consecutive menstrual cycles. In an open, cross-over, controlled design, patients were randomized to receive either DCF per os or GTN patches the first days of menses, when menstrual cramps became unendurable. In the subsequent cycle the other treatment was used. Patients received up to 3 doses/day of 50 mg DCF or 2.5 mg/24 h transdermal GTN for the first 3 days of the cycle, according to their needs. The participants recorded menstrual symptoms and possible side-effects at different times (0, 30, 60, 120 minutes) after the first dose of medication on the first day of the cycle, with both drugs. The difference in pain intensity score (DPI) was the main outcome variable. Both treatments significantly reduced DPI by the 30th minute (GTN, -12.8 +/- 17.9; DCF, -18.9 +/- 16.6). However, DCF continued to be effective in reducing pelvic pain for two hours, whereas GTN scores remained more or less stable after 30 min and significantly higher than those for DFC (after one hour: GTN, -12.8 +/- 17.9; DFC, -18.9 +/- 16.6 and after two hours: GTN, -23.7 +/- 20.5; DFC, -59.7 +/- 17.9, p = 0.0001). Low back pain was also relieved by both drugs. Headache was significantly increased by GTN but not by DCF. Eight patients stopped using GTN because headache--attributed to its use--became intolerable. These findings indicate that GTN has a reduced efficacy and tolerability by comparison with DCF in the treatment of primary dysmenorrhea.","[{'text': 'glyceryl trinitrate', 'type': 'Chemical', 'start': 16, 'end': 35, 'mesh': 'D005996'}, {'text': 'diclofenac', 'type': 'Chemical', 'start': 41, 'end': 51, 'mesh': 'D004008'}, {'text': 'dysmenorrhea', 'type': 'Disease', 'start': 81, 'end': 93, 'mesh': 'D004412'}, {'text': 'dysmenorrhea', 'type': 'Disease', 'start': 142, 'end': 154, 'mesh': 'D004412'}, {'text': 'prostaglandins', 'type': 'Chemical', 'start': 258, 'end': 272, 'mesh': 'D011453'}, {'text': 'nitric oxide', 'type': 'Chemical', 'start': 474, 'end': 486, 'mesh': 'D009569'}, {'text': 'NO', 'type': 'Chemical', 'start': 488, 'end': 490, 'mesh': 'D009569'}, {'text': 'glyceryl trinitrate', 'type': 'Chemical', 'start': 555, 'end': 574, 'mesh': 'D005996'}, {'text': 'GTN', 'type': 'Chemical', 'start': 576, 'end': 579, 'mesh': 'D005996'}, {'text': 'NO', 'type': 'Chemical', 'start': 585, 'end': 587, 'mesh': 'D009569'}, {'text': 'dysmenorrhea', 'type': 'Disease', 'start': 624, 'end': 636, 'mesh': 'D004412'}, {'text': 'diclofenac', 'type': 'Chemical', 'start': 656, 'end': 666, 'mesh': 'D004008'}, {'text': 'DCF', 'type': 'Chemical', 'start': 668, 'end': 671, 'mesh': 'D004008'}, {'text': 'dysmenorrhea', 'type': 'Disease', 'start': 734, 'end': 746, 'mesh': 'D004412'}, {'text': 'DCF', 'type': 'Chemical', 'start': 887, 'end': 890, 'mesh': 'D004008'}, {'text': 'GTN', 'type': 'Chemical', 'start': 901, 'end': 904, 'mesh': 'D005996'}, {'text': 'DCF', 'type': 'Chemical', 'start': 1080, 'end': 1083, 'mesh': 'D004008'}, {'text': 'GTN', 'type': 'Chemical', 'start': 1111, 'end': 1114, 'mesh': 'D005996'}, {'text': 'pain', 'type': 'Disease', 'start': 1392, 'end': 1396, 'mesh': 'D010146'}, {'text': 'GTN', 'type': 'Chemical', 'start': 1512, 'end': 1515, 'mesh': 'D005996'}, {'text': 'DCF', 'type': 'Chemical', 'start': 1533, 'end': 1536, 'mesh': 'D004008'}, {'text': 'DCF', 'type': 'Chemical', 'start': 1564, 'end': 1567, 'mesh': 'D004008'}, {'text': 'pelvic pain', 'type': 'Disease', 'start': 1606, 'end': 1617, 'mesh': 'D017699'}, {'text': 'GTN', 'type': 'Chemical', 'start': 1641, 'end': 1644, 'mesh': 'D005996'}, {'text': 'GTN', 'type': 'Chemical', 'start': 1755, 'end': 1758, 'mesh': 'D005996'}, {'text': 'GTN', 'type': 'Chemical', 'start': 1817, 'end': 1820, 'mesh': 'D005996'}, {'text': 'Low back pain', 'type': 'Disease', 'start': 1872, 'end': 1885, 'mesh': 'D017116'}, {'text': 'Headache', 'type': 'Disease', 'start': 1919, 'end': 1927, 'mesh': 'D006261'}, {'text': 'GTN', 'type': 'Chemical', 'start': 1959, 'end': 1962, 'mesh': 'D005996'}, {'text': 'DCF', 'type': 'Chemical', 'start': 1974, 'end': 1977, 'mesh': 'D004008'}, {'text': 'GTN', 'type': 'Chemical', 'start': 2008, 'end': 2011, 'mesh': 'D005996'}, {'text': 'headache', 'type': 'Disease', 'start': 2020, 'end': 2028, 'mesh': 'D006261'}, {'text': 'GTN', 'type': 'Chemical', 'start': 2102, 'end': 2105, 'mesh': 'D005996'}, {'text': 'DCF', 'type': 'Chemical', 'start': 2165, 'end': 2168, 'mesh': 'D004008'}, {'text': 'dysmenorrhea', 'type': 'Disease', 'start': 2197, 'end': 2209, 'mesh': 'D004412'}]"
+1358,11936424,"Temocapril, a long-acting non-SH group angiotensin converting enzyme inhibitor, modulates glomerular injury in chronic puromycin aminonucleoside nephrosis.","The purpose of the present study was to determine whether chronic administration of temocapril, a long-acting non-SH group angiotensin converting enzyme (ACE) inhibitor, reduced proteinuria, inhibited glomerular hypertrophy and prevented glomerulosclerosis in chronic puromycin aminonucleoside (PAN) - induced nephrotic rats. Nephrosis was induced by injection of PAN (15mg/100g body weight) in male Sprague-Dawley (SD) rats. Four groups were used, i) the PAN group (14), ii) PAN/temocapril (13), iii) temocapril (14) and iv) untreated controls (15). Temocapril (8 mg/kg/day) was administered to the rats which were killed at weeks 4, 14 or 20. At each time point, systolic blood pressure (BP), urinary protein excretion and renal histopathological findings were evaluated, and morphometric image analysis was done. Systolic BP in the PAN group was significantly high at 4, 14 and 20 weeks, but was normal in the PAN/temocapril group. Urinary protein excretion in the PAN group increased significantly, peaking at 8 days, then decreased at 4 weeks, but rose again significantly at 14 and 20 weeks. Temocapril did not attenuate proteinuria at 8 days, but it did markedly lower it from weeks 4 to 20. The glomerulosclerosis index (GSI) was 6.21 % at 4 weeks and respectively 25.35 % and 30.49 % at 14 and 20 weeks in the PAN group. There was a significant correlation between urinary protein excretion and GSI (r = 0.808, p < 0.0001). The ratio of glomerular tuft area to the area of Bowman's capsules (GT/BC) in the PAN group was significantly increased, but it was significantly lower in the PAN/temocapril group. It appears that temocapril was effective in retarding renal progression and protected renal function in PAN neprotic rats.","[{'text': 'Temocapril', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'C055603'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 39, 'end': 50, 'mesh': 'D000809'}, {'text': 'glomerular injury', 'type': 'Disease', 'start': 90, 'end': 107, 'mesh': 'D007674'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 119, 'end': 144, 'mesh': 'D011692'}, {'text': 'nephrosis', 'type': 'Disease', 'start': 145, 'end': 154, 'mesh': 'D009401'}, {'text': 'temocapril', 'type': 'Chemical', 'start': 240, 'end': 250, 'mesh': 'C055603'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 279, 'end': 290, 'mesh': 'D000809'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 334, 'end': 345, 'mesh': 'D011507'}, {'text': 'hypertrophy', 'type': 'Disease', 'start': 368, 'end': 379, 'mesh': 'D006984'}, {'text': 'glomerulosclerosis', 'type': 'Disease', 'start': 394, 'end': 412, 'mesh': 'D005921'}, {'text': 'puromycin aminonucleoside', 'type': 'Chemical', 'start': 424, 'end': 449, 'mesh': 'D011692'}, {'text': 'PAN', 'type': 'Chemical', 'start': 451, 'end': 454, 'mesh': 'D011692'}, {'text': 'nephrotic', 'type': 'Disease', 'start': 466, 'end': 475, 'mesh': 'D009404'}, {'text': 'Nephrosis', 'type': 'Disease', 'start': 482, 'end': 491, 'mesh': 'D009401'}, {'text': 'PAN', 'type': 'Chemical', 'start': 520, 'end': 523, 'mesh': 'D011692'}, {'text': 'PAN', 'type': 'Chemical', 'start': 612, 'end': 615, 'mesh': 'D011692'}, {'text': 'PAN', 'type': 'Chemical', 'start': 632, 'end': 635, 'mesh': 'D011692'}, {'text': 'temocapril', 'type': 'Chemical', 'start': 636, 'end': 646, 'mesh': 'C055603'}, {'text': 'temocapril', 'type': 'Chemical', 'start': 658, 'end': 668, 'mesh': 'C055603'}, {'text': 'Temocapril', 'type': 'Chemical', 'start': 707, 'end': 717, 'mesh': 'C055603'}, {'text': 'PAN', 'type': 'Chemical', 'start': 991, 'end': 994, 'mesh': 'D011692'}, {'text': 'PAN', 'type': 'Chemical', 'start': 1069, 'end': 1072, 'mesh': 'D011692'}, {'text': 'temocapril', 'type': 'Chemical', 'start': 1073, 'end': 1083, 'mesh': 'C055603'}, {'text': 'PAN', 'type': 'Chemical', 'start': 1124, 'end': 1127, 'mesh': 'D011692'}, {'text': 'Temocapril', 'type': 'Chemical', 'start': 1254, 'end': 1264, 'mesh': 'C055603'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1283, 'end': 1294, 'mesh': 'D011507'}, {'text': 'glomerulosclerosis', 'type': 'Disease', 'start': 1359, 'end': 1377, 'mesh': 'D005921'}, {'text': 'PAN', 'type': 'Chemical', 'start': 1475, 'end': 1478, 'mesh': 'D011692'}, {'text': 'PAN', 'type': 'Chemical', 'start': 1671, 'end': 1674, 'mesh': 'D011692'}, {'text': 'PAN', 'type': 'Chemical', 'start': 1748, 'end': 1751, 'mesh': 'D011692'}, {'text': 'temocapril', 'type': 'Chemical', 'start': 1752, 'end': 1762, 'mesh': 'C055603'}, {'text': 'temocapril', 'type': 'Chemical', 'start': 1786, 'end': 1796, 'mesh': 'C055603'}, {'text': 'PAN', 'type': 'Chemical', 'start': 1874, 'end': 1877, 'mesh': 'D011692'}, {'text': 'neprotic', 'type': 'Disease', 'start': 1878, 'end': 1886, 'mesh': 'D009401'}]"
+1359,11988250,Pulmonary hypertension after ibuprofen prophylaxis in very preterm infants.,We report three cases of severe hypoxaemia after ibuprofen administration during a randomised controlled trial of prophylactic treatment of patent ductus arteriosus with ibuprofen in premature infants born at less than 28 weeks of gestation. Echocardiography showed severely decreased pulmonary blood flow. Hypoxaemia resolved quickly on inhaled nitric oxide therapy. We suggest that investigators involved in similar trials pay close attention to pulmonary pressure if hypoxaemia occurs after prophylactic administration of ibuprofen.,"[{'text': 'Pulmonary hypertension', 'type': 'Disease', 'start': 0, 'end': 22, 'mesh': 'D006976'}, {'text': 'ibuprofen', 'type': 'Chemical', 'start': 29, 'end': 38, 'mesh': 'D007052'}, {'text': 'hypoxaemia', 'type': 'Disease', 'start': 108, 'end': 118, 'mesh': 'D000860'}, {'text': 'ibuprofen', 'type': 'Chemical', 'start': 125, 'end': 134, 'mesh': 'D007052'}, {'text': 'patent ductus arteriosus', 'type': 'Disease', 'start': 216, 'end': 240, 'mesh': 'D004374'}, {'text': 'ibuprofen', 'type': 'Chemical', 'start': 246, 'end': 255, 'mesh': 'D007052'}, {'text': 'Hypoxaemia', 'type': 'Disease', 'start': 383, 'end': 393, 'mesh': 'D000860'}, {'text': 'nitric oxide', 'type': 'Chemical', 'start': 422, 'end': 434, 'mesh': 'D009569'}, {'text': 'hypoxaemia', 'type': 'Disease', 'start': 546, 'end': 556, 'mesh': 'D000860'}, {'text': 'ibuprofen', 'type': 'Chemical', 'start': 601, 'end': 610, 'mesh': 'D007052'}]"
+1360,12051122,Hyponatremia and syndrome of inappropriate anti-diuretic hormone reported with the use of Vincristine: an over-representation of Asians?,"PURPOSE: This retrospective study used a pharmaceutical company's global safety database to determine the reporting rate of hyponatremia and/or syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) among vincristine-treated patients and to explore the possibility of at-risk population subgroups. METHOD: We searched the Eli Lilly and Company's computerized adverse event database for all reported cases of hyponatremia and/or SIADH as of 1 November 1999 that had been reported during the use of vincristine. RESULTS: A total of 76 cases of hyponatremia and/or SIADH associated with vincristine use were identified. The overall reporting rate was estimated to be 1.3/100,000 treated patients. The average age of patients was 35.6 +/- 28.3 years, and 62% were males. Approximately 75% of the patients were receiving treatment for leukemia or lymphoma. Among the 39 reports that included information on race, the racial distribution was: 1 Black, 3 Caucasian, and 35 Asian. CONCLUSION: Our data suggest that Asian patients may be at increased risk of hyponatremia and/or SIADH associated with vincristine use. Although the overall reported rate of SIADH associated with vincristine is very low, physicians caring for Asian oncology patients should be aware of this potential serious but reversible adverse event.","[{'text': 'Hyponatremia', 'type': 'Disease', 'start': 0, 'end': 12, 'mesh': 'D007010'}, {'text': 'syndrome of inappropriate anti-diuretic hormone', 'type': 'Disease', 'start': 17, 'end': 64, 'mesh': 'D007177'}, {'text': 'Vincristine', 'type': 'Chemical', 'start': 90, 'end': 101, 'mesh': 'D014750'}, {'text': 'hyponatremia', 'type': 'Disease', 'start': 261, 'end': 273, 'mesh': 'D007010'}, {'text': 'syndrome of inappropriate secretion of anti-diuretic hormone', 'type': 'Disease', 'start': 281, 'end': 341, 'mesh': 'D007177'}, {'text': 'SIADH', 'type': 'Disease', 'start': 343, 'end': 348, 'mesh': 'D007177'}, {'text': 'vincristine', 'type': 'Chemical', 'start': 356, 'end': 367, 'mesh': 'D014750'}, {'text': 'hyponatremia', 'type': 'Disease', 'start': 559, 'end': 571, 'mesh': 'D007010'}, {'text': 'SIADH', 'type': 'Disease', 'start': 579, 'end': 584, 'mesh': 'D007177'}, {'text': 'vincristine', 'type': 'Chemical', 'start': 648, 'end': 659, 'mesh': 'D014750'}, {'text': 'hyponatremia', 'type': 'Disease', 'start': 693, 'end': 705, 'mesh': 'D007010'}, {'text': 'SIADH', 'type': 'Disease', 'start': 713, 'end': 718, 'mesh': 'D007177'}, {'text': 'vincristine', 'type': 'Chemical', 'start': 735, 'end': 746, 'mesh': 'D014750'}, {'text': 'leukemia', 'type': 'Disease', 'start': 981, 'end': 989, 'mesh': 'D007938'}, {'text': 'lymphoma', 'type': 'Disease', 'start': 993, 'end': 1001, 'mesh': 'D008223'}, {'text': 'hyponatremia', 'type': 'Disease', 'start': 1201, 'end': 1213, 'mesh': 'D007010'}, {'text': 'SIADH', 'type': 'Disease', 'start': 1221, 'end': 1226, 'mesh': 'D007177'}, {'text': 'vincristine', 'type': 'Chemical', 'start': 1243, 'end': 1254, 'mesh': 'D014750'}, {'text': 'SIADH', 'type': 'Disease', 'start': 1298, 'end': 1303, 'mesh': 'D007177'}, {'text': 'vincristine', 'type': 'Chemical', 'start': 1320, 'end': 1331, 'mesh': 'D014750'}]"
+1361,12059909,Delayed toxicity of cyclophosphamide on the bladder of DBA/2 and C57BL/6 female mouse.,"The present study describes the delayed development of a severe bladder pathology in a susceptible strain of mice (DBA/2) but not in a resistant strain (C57BL/6) when both were treated with a single 300 mg/kg dose of cyclophosphamide (CY). Inbred DBA/2 and C57BL/6 female mice were injected with CY, and the effect of the drug on the bladder was assessed during 100 days by light microscopy using different staining procedures, and after 30 days by conventional electron microscopy. Early CY toxicity caused a typical haemorrhagic cystitis in both strains that was completely repaired in about 7-10 days. After 30 days of CY injection ulcerous and non-ulcerous forms of chronic cystitis appeared in 86% of DBA/2 mice but only in 4% of C57BL/6 mice. Delayed cystitis was characterized by infiltration and transepithelial passage into the lumen of inflammatory cells and by frequent exfoliation of the urothelium. Mast cells appeared in the connective and muscular layers of the bladder at a much higher number in DBA/2 mice than in C57BL/6 mice or untreated controls. Electron microscopy disclosed the absence of the typical discoidal vesicles normally present in the cytoplasm of surface cells. Instead, numerous abnormal vesicles containing one or several dark granules were observed in the cytoplasm of cells from all the epithelial layers. Delayed cystitis still persisted in DBA/2 mice 100 days after treatment. These results indicate that delayed toxicity of CY in female DBA/2 mice causes a bladder pathology that is not observed in C57BL/6 mice. This pathology resembles interstitial cystitis in humans and could perhaps be used as an animal model for studies on the disease.","[{'text': 'toxicity', 'type': 'Disease', 'start': 8, 'end': 16, 'mesh': 'D064420'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 20, 'end': 36, 'mesh': 'D003520'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 304, 'end': 320, 'mesh': 'D003520'}, {'text': 'CY', 'type': 'Chemical', 'start': 322, 'end': 324, 'mesh': 'D003520'}, {'text': 'CY', 'type': 'Chemical', 'start': 383, 'end': 385, 'mesh': 'D003520'}, {'text': 'CY', 'type': 'Chemical', 'start': 576, 'end': 578, 'mesh': 'D003520'}, {'text': 'toxicity', 'type': 'Disease', 'start': 579, 'end': 587, 'mesh': 'D064420'}, {'text': 'haemorrhagic', 'type': 'Disease', 'start': 605, 'end': 617, 'mesh': 'D006470'}, {'text': 'cystitis', 'type': 'Disease', 'start': 618, 'end': 626, 'mesh': 'D003556'}, {'text': 'CY', 'type': 'Chemical', 'start': 709, 'end': 711, 'mesh': 'D003520'}, {'text': 'cystitis', 'type': 'Disease', 'start': 765, 'end': 773, 'mesh': 'D003556'}, {'text': 'cystitis', 'type': 'Disease', 'start': 844, 'end': 852, 'mesh': 'D003556'}, {'text': 'cystitis', 'type': 'Disease', 'start': 1438, 'end': 1446, 'mesh': 'D003556'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1539, 'end': 1547, 'mesh': 'D064420'}, {'text': 'CY', 'type': 'Chemical', 'start': 1551, 'end': 1553, 'mesh': 'D003520'}, {'text': 'interstitial cystitis', 'type': 'Disease', 'start': 1665, 'end': 1686, 'mesh': 'D018856'}]"
+1362,12119460,High-dose 5-fluorouracil / folinic acid in combination with three-weekly mitomycin C in the treatment of advanced gastric cancer. A phase II study.,"BACKGROUND: The 24-hour continuous infusion of 5-fluorouracil (5-FU) and folinic acid (FA) as part of several new multidrug chemotherapy regimens in advanced gastric cancer (AGC) has shown to be effective, with low toxicity. In a previous phase II study with 3-weekly bolus 5-FU, FA and mitomycin C (MMC) we found a low toxicity rate and response rates comparable to those of regimens such as ELF, FAM or FAMTX, and a promising median overall survival. In order to improve this MMC-dependent schedule we initiated a phase II study with high-dose 5-FU/FA and 3-weekly bolus MMC. PATIENTS AND METHODS: From February, 1998 to September, 2000 we recruited 33 patients with AGC to receive weekly 24-hour 5-FU 2,600 mg/m(2) preceded by 2-hour FA 500 mg/m(2) for 6 weeks, followed by a 2-week rest period. Bolus MMC 10 mg/m(2) was added in 3-weekly intervals. Treatment given on an outpatient basis, using portable pump systems, was repeated on day 57. Patients' characteristics were: male/female ratio 20/13; median age 57 (27-75) years; median WHO status 1 (0-2). 18 patients had a primary AGC, and 15 showed a relapsed AGC. Median follow-up was 11.8 months (range of those surviving: 2.7-11.8 months). RESULTS: 32 patients were evaluable for response - complete remission 9.1% (n = 3), partial remission 45.5% (n = 15), no change 27.3% (n = 9), progressive disease 15.1% (n = 5). Median overall survival time was 10.2 months [95% confidence interval (CI): 8.7-11.6], and median progression-free survival time was 7.6 months (95% CI: 4.4-10.9). The worst toxicities (%) observed were (CTC-NCI 1/2/3): leukopenia 45.5/18.2/6.1, thrombocytopenia 33.3/9.1/6.1, vomitus 24.2/9.1/0, diarrhea 36.4/6.1/3.0, stomatitis 18.2/9.1/0, hand-foot syndrome 12.1/0/0. Two patients developed hemolytic-uremic syndrome (HUS). CONCLUSIONS: High-dose 5-FU/FA/MMC is an effective and well-tolerated outpatient regimen for AGC (objective response rate 54.6%). It may serve as an alternative to cisplatin-containing regimens; however, it has to be considered that possibly HUS may occur.","[{'text': '5-fluorouracil', 'type': 'Chemical', 'start': 10, 'end': 24, 'mesh': 'D005472'}, {'text': 'folinic acid', 'type': 'Chemical', 'start': 27, 'end': 39, 'mesh': 'D002955'}, {'text': 'mitomycin C', 'type': 'Chemical', 'start': 73, 'end': 84, 'mesh': 'D016685'}, {'text': 'gastric cancer', 'type': 'Disease', 'start': 114, 'end': 128, 'mesh': 'D013274'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 195, 'end': 209, 'mesh': 'D005472'}, {'text': '5-FU', 'type': 'Chemical', 'start': 211, 'end': 215, 'mesh': 'D005472'}, {'text': 'folinic acid', 'type': 'Chemical', 'start': 221, 'end': 233, 'mesh': 'D002955'}, {'text': 'FA', 'type': 'Chemical', 'start': 235, 'end': 237, 'mesh': 'D002955'}, {'text': 'gastric cancer', 'type': 'Disease', 'start': 306, 'end': 320, 'mesh': 'D013274'}, {'text': 'AGC', 'type': 'Disease', 'start': 322, 'end': 325, 'mesh': 'D013274'}, {'text': 'toxicity', 'type': 'Disease', 'start': 363, 'end': 371, 'mesh': 'D064420'}, {'text': '5-FU', 'type': 'Chemical', 'start': 422, 'end': 426, 'mesh': 'D005472'}, {'text': 'FA', 'type': 'Chemical', 'start': 428, 'end': 430, 'mesh': 'D002955'}, {'text': 'mitomycin C', 'type': 'Chemical', 'start': 435, 'end': 446, 'mesh': 'D016685'}, {'text': 'MMC', 'type': 'Chemical', 'start': 448, 'end': 451, 'mesh': 'D016685'}, {'text': 'toxicity', 'type': 'Disease', 'start': 468, 'end': 476, 'mesh': 'D064420'}, {'text': 'MMC', 'type': 'Chemical', 'start': 626, 'end': 629, 'mesh': 'D016685'}, {'text': '5-FU', 'type': 'Chemical', 'start': 694, 'end': 698, 'mesh': 'D005472'}, {'text': 'FA', 'type': 'Chemical', 'start': 699, 'end': 701, 'mesh': 'D002955'}, {'text': 'MMC', 'type': 'Chemical', 'start': 721, 'end': 724, 'mesh': 'D016685'}, {'text': 'AGC', 'type': 'Disease', 'start': 817, 'end': 820, 'mesh': 'D013274'}, {'text': '5-FU', 'type': 'Chemical', 'start': 847, 'end': 851, 'mesh': 'D005472'}, {'text': 'FA', 'type': 'Chemical', 'start': 885, 'end': 887, 'mesh': 'D002955'}, {'text': 'MMC', 'type': 'Chemical', 'start': 953, 'end': 956, 'mesh': 'D016685'}, {'text': 'AGC', 'type': 'Disease', 'start': 1233, 'end': 1236, 'mesh': 'D013274'}, {'text': 'AGC', 'type': 'Disease', 'start': 1263, 'end': 1266, 'mesh': 'D013274'}, {'text': 'toxicities', 'type': 'Disease', 'start': 1698, 'end': 1708, 'mesh': 'D064420'}, {'text': 'leukopenia', 'type': 'Disease', 'start': 1744, 'end': 1754, 'mesh': 'D007970'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 1770, 'end': 1786, 'mesh': 'D013921'}, {'text': 'vomitus', 'type': 'Disease', 'start': 1801, 'end': 1808, 'mesh': 'D014839'}, {'text': 'diarrhea', 'type': 'Disease', 'start': 1821, 'end': 1829, 'mesh': 'D003967'}, {'text': 'stomatitis', 'type': 'Disease', 'start': 1844, 'end': 1854, 'mesh': 'D013280'}, {'text': 'hand-foot syndrome', 'type': 'Disease', 'start': 1867, 'end': 1885, 'mesh': 'D060831'}, {'text': 'hemolytic-uremic syndrome', 'type': 'Disease', 'start': 1919, 'end': 1944, 'mesh': 'D006463'}, {'text': 'HUS', 'type': 'Disease', 'start': 1946, 'end': 1949, 'mesh': 'D006463'}, {'text': '5-FU', 'type': 'Chemical', 'start': 1975, 'end': 1979, 'mesh': 'D005472'}, {'text': 'FA', 'type': 'Chemical', 'start': 1980, 'end': 1982, 'mesh': 'D002955'}, {'text': 'MMC', 'type': 'Chemical', 'start': 1983, 'end': 1986, 'mesh': 'D016685'}, {'text': 'AGC', 'type': 'Disease', 'start': 2045, 'end': 2048, 'mesh': 'D013274'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 2116, 'end': 2125, 'mesh': 'D002945'}, {'text': 'HUS', 'type': 'Disease', 'start': 2194, 'end': 2197, 'mesh': 'D006463'}]"
+1363,12165618,Persistent sterile leukocyturia is associated with impaired renal function in human immunodeficiency virus type 1-infected children treated with indinavir.,"BACKGROUND: Prolonged administration of indinavir is associated with the occurrence of a variety of renal complications in adults. These well-documented side effects have restricted the use of this potent protease inhibitor in children. DESIGN: A prospective study to monitor indinavir-related nephrotoxicity in a cohort of 30 human immunodeficiency virus type 1-infected children treated with indinavir. METHODS: Urinary pH, albumin, creatinine, the presence of erythrocytes, leukocytes, bacteria and crystals, and culture were analyzed every 3 months for 96 weeks. Serum creatinine levels were routinely determined at the same time points. Steady-state pharmacokinetics of indinavir were done at week 4 after the initiation of indinavir. RESULTS: The cumulative incidence of persistent sterile leukocyturia (> or =75 cells/ micro L in at least 2 consecutive visits) after 96 weeks was 53%. Persistent sterile leukocyturia was frequently associated with a mild increase in the urine albumin/creatinine ratio and by microscopic hematuria. The cumulative incidence of serum creatinine levels >50% above normal was 33% after 96 weeks. Children with persistent sterile leukocyturia more frequently had serum creatinine levels of 50% above normal than those children without persistent sterile leukocyturia. In children younger than 5.6 years, persistent sterile leukocyturia was significantly more frequent than in older children. A higher cumulative incidence of persistent leukocyturia was found in children with an area under the curve >19 mg/L x h or a peak serum level of indinavir >12 mg/L. In 4 children, indinavir was discontinued because of nephrotoxicity. Subsequently, the serum creatinine levels decreased, the urine albumin/creatinine ratios returned to zero, and the leukocyturia disappeared within 3 months. CONCLUSIONS: Children treated with indinavir have a high cumulative incidence of persistent sterile leukocyturia. Children with persistent sterile leukocyturia more frequently had an increase in serum creatinine levels of >50% above normal. Younger children have an additional risk for renal complications. The impairment of the renal function in these children occurred in the absence of clinical symptoms of nephrolithiasis. Indinavir-associated nephrotoxicity must be monitored closely, especially in children with risk factors such as persistent sterile leukocyturia, age <5.6 years, an area under the curve of indinavir >19 mg/L x h, and a C(max) >12 mg/L.","[{'text': 'leukocyturia', 'type': 'Disease', 'start': 19, 'end': 31, 'mesh': '-1'}, {'text': 'impaired renal function', 'type': 'Disease', 'start': 51, 'end': 74, 'mesh': 'D007674'}, {'text': 'human immunodeficiency virus type 1-infected', 'type': 'Disease', 'start': 78, 'end': 122, 'mesh': 'D015658'}, {'text': 'indinavir', 'type': 'Chemical', 'start': 145, 'end': 154, 'mesh': 'D019469'}, {'text': 'indinavir', 'type': 'Chemical', 'start': 196, 'end': 205, 'mesh': 'D019469'}, {'text': 'indinavir', 'type': 'Chemical', 'start': 432, 'end': 441, 'mesh': 'D019469'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 450, 'end': 464, 'mesh': 'D007674'}, {'text': 'human immunodeficiency virus type 1-infected', 'type': 'Disease', 'start': 483, 'end': 527, 'mesh': 'D015658'}, {'text': 'indinavir', 'type': 'Chemical', 'start': 550, 'end': 559, 'mesh': 'D019469'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 591, 'end': 601, 'mesh': 'D003404'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 729, 'end': 739, 'mesh': 'D003404'}, {'text': 'indinavir', 'type': 'Chemical', 'start': 831, 'end': 840, 'mesh': 'D019469'}, {'text': 'indinavir', 'type': 'Chemical', 'start': 885, 'end': 894, 'mesh': 'D019469'}, {'text': 'leukocyturia', 'type': 'Disease', 'start': 952, 'end': 964, 'mesh': '-1'}, {'text': 'leukocyturia', 'type': 'Disease', 'start': 1067, 'end': 1079, 'mesh': '-1'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1148, 'end': 1158, 'mesh': 'D003404'}, {'text': 'hematuria', 'type': 'Disease', 'start': 1184, 'end': 1193, 'mesh': 'D006417'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1229, 'end': 1239, 'mesh': 'D003404'}, {'text': 'leukocyturia', 'type': 'Disease', 'start': 1322, 'end': 1334, 'mesh': '-1'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1361, 'end': 1371, 'mesh': 'D003404'}, {'text': 'leukocyturia', 'type': 'Disease', 'start': 1446, 'end': 1458, 'mesh': '-1'}, {'text': 'leukocyturia', 'type': 'Disease', 'start': 1515, 'end': 1527, 'mesh': '-1'}, {'text': 'leukocyturia', 'type': 'Disease', 'start': 1628, 'end': 1640, 'mesh': '-1'}, {'text': 'indinavir', 'type': 'Chemical', 'start': 1730, 'end': 1739, 'mesh': 'D019469'}, {'text': 'indinavir', 'type': 'Chemical', 'start': 1765, 'end': 1774, 'mesh': 'D019469'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1803, 'end': 1817, 'mesh': 'D007674'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1843, 'end': 1853, 'mesh': 'D003404'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1890, 'end': 1900, 'mesh': 'D003404'}, {'text': 'leukocyturia', 'type': 'Disease', 'start': 1934, 'end': 1946, 'mesh': '-1'}, {'text': 'indinavir', 'type': 'Chemical', 'start': 2011, 'end': 2020, 'mesh': 'D019469'}, {'text': 'leukocyturia', 'type': 'Disease', 'start': 2076, 'end': 2088, 'mesh': '-1'}, {'text': 'leukocyturia', 'type': 'Disease', 'start': 2123, 'end': 2135, 'mesh': '-1'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 2177, 'end': 2187, 'mesh': 'D003404'}, {'text': 'impairment of the renal function', 'type': 'Disease', 'start': 2287, 'end': 2319, 'mesh': 'D007674'}, {'text': 'nephrolithiasis', 'type': 'Disease', 'start': 2386, 'end': 2401, 'mesh': 'D053040'}, {'text': 'Indinavir', 'type': 'Chemical', 'start': 2403, 'end': 2412, 'mesh': 'D019469'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 2424, 'end': 2438, 'mesh': 'D007674'}, {'text': 'leukocyturia', 'type': 'Disease', 'start': 2534, 'end': 2546, 'mesh': '-1'}, {'text': 'indinavir', 'type': 'Chemical', 'start': 2591, 'end': 2600, 'mesh': 'D019469'}]"
+1364,12359538,Utility of troponin I in patients with cocaine-associated chest pain.,"Baseline electrocardiogram abnormalities and market elevations not associated with myocardial necrosis make accurate diagnosis of myocardial infarction (MI) difficult in patients with cocaine-associated chest pain. Troponin sampling may offer greater diagnostic utility in these patients. OBJECTIVE: To assess outcomes based on troponin positivity in patients with cocaine chest pain admitted for exclusion of MI. METHODS: Outcomes were examined in patients admitted for possible MI after cocaine use. All patients underwent a rapid rule-in protocol that included serial sampling of creatine kinase (CK), CK-MB, and cardiac troponin I (cTnI) over eight hours. Outcomes included CK-MB MI (CK-MB >or= 8 ng/mL with a relative index [(CK-MB x 100)/total CK] >or= 4, cardiac death, and significant coronary disease (>or=50%). RESULTS: Of the 246 admitted patients, 34 (14%) met CK-MB criteria for MI and 38 (16%) had cTnI elevations. Angiography was performed in 29 of 38 patients who were cTnI-positive, with significant disease present in 25 (86%). Three of the four patients without significant disease who had cTnI elevations met CK-MB criteria for MI, and the other had a peak CK-MB level of 13 ng/mL. Sensitivities, specificities, and positive and negative likelihood ratios for predicting cardiac death or significant disease were high for both CK-MB MI and cTnI and were not significantly different. CONCLUSIONS: Most patients with cTnI elevations meet CK-MB criteria for MI, as well as have a high incidence of underlying significant disease. Troponin appears to have an equivalent diagnostic accuracy compared with CK-MB for diagnosing necrosis in patients with cocaine-associated chest pain and suspected MI.","[{'text': 'cocaine', 'type': 'Chemical', 'start': 39, 'end': 46, 'mesh': 'D003042'}, {'text': 'chest pain', 'type': 'Disease', 'start': 58, 'end': 68, 'mesh': 'D002637'}, {'text': 'myocardial necrosis', 'type': 'Disease', 'start': 153, 'end': 172, 'mesh': 'D009202'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 200, 'end': 221, 'mesh': 'D009203'}, {'text': 'MI', 'type': 'Disease', 'start': 223, 'end': 225, 'mesh': 'D009203'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 254, 'end': 261, 'mesh': 'D003042'}, {'text': 'chest pain', 'type': 'Disease', 'start': 273, 'end': 283, 'mesh': 'D002637'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 435, 'end': 442, 'mesh': 'D003042'}, {'text': 'chest pain', 'type': 'Disease', 'start': 443, 'end': 453, 'mesh': 'D002637'}, {'text': 'MI', 'type': 'Disease', 'start': 480, 'end': 482, 'mesh': 'D009203'}, {'text': 'MI', 'type': 'Disease', 'start': 550, 'end': 552, 'mesh': 'D009203'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 559, 'end': 566, 'mesh': 'D003042'}, {'text': 'creatine', 'type': 'Chemical', 'start': 653, 'end': 661, 'mesh': 'D003401'}, {'text': 'MI', 'type': 'Disease', 'start': 754, 'end': 756, 'mesh': 'D009203'}, {'text': 'cardiac death', 'type': 'Disease', 'start': 832, 'end': 845, 'mesh': 'D003643'}, {'text': 'coronary disease', 'type': 'Disease', 'start': 863, 'end': 879, 'mesh': 'D003327'}, {'text': 'MI', 'type': 'Disease', 'start': 962, 'end': 964, 'mesh': 'D009203'}, {'text': 'MI', 'type': 'Disease', 'start': 1218, 'end': 1220, 'mesh': 'D009203'}, {'text': 'cardiac death', 'type': 'Disease', 'start': 1361, 'end': 1374, 'mesh': 'D003643'}, {'text': 'MI', 'type': 'Disease', 'start': 1423, 'end': 1425, 'mesh': 'D009203'}, {'text': 'MI', 'type': 'Disease', 'start': 1545, 'end': 1547, 'mesh': 'D009203'}, {'text': 'necrosis', 'type': 'Disease', 'start': 1711, 'end': 1719, 'mesh': 'D009336'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1737, 'end': 1744, 'mesh': 'D003042'}, {'text': 'chest pain', 'type': 'Disease', 'start': 1756, 'end': 1766, 'mesh': 'D002637'}, {'text': 'MI', 'type': 'Disease', 'start': 1781, 'end': 1783, 'mesh': 'D009203'}]"
+1365,12372954,Acute interstitial nephritis due to nicergoline (Sermion).,"We report a case of acute interstitial nephritis (AIN) due to nicergoline (Sermion). A 50-year-old patient admitted to our hospital for fever and acute renal failure. Before admission, he had been taking nicergoline and bendazac lysine due to retinal vein occlusion at ophthalmologic department. Thereafter, he experienced intermittent fever and skin rash. On admission, clinical symptoms (i.e. arthralgia and fever) and laboratory findings (i.e. eosinophilia and renal failure) suggested AIN, and which was confirmed by pathologic findings on renal biopsy. A lymphocyte transformation test demonstrated a positive result against nicergoline. Treatment was consisted of withdrawal of nicergoline and intravenous methylprednisolone, and his renal function was completely recovered. To our knowledge, this is the first report of nicergoline-associated AIN.","[{'text': 'interstitial nephritis', 'type': 'Disease', 'start': 6, 'end': 28, 'mesh': 'D009395'}, {'text': 'nicergoline', 'type': 'Chemical', 'start': 36, 'end': 47, 'mesh': 'D009530'}, {'text': 'Sermion', 'type': 'Chemical', 'start': 49, 'end': 56, 'mesh': 'D009530'}, {'text': 'interstitial nephritis', 'type': 'Disease', 'start': 85, 'end': 107, 'mesh': 'D009395'}, {'text': 'AIN', 'type': 'Disease', 'start': 109, 'end': 112, 'mesh': 'D009395'}, {'text': 'nicergoline', 'type': 'Chemical', 'start': 121, 'end': 132, 'mesh': 'D009530'}, {'text': 'Sermion', 'type': 'Chemical', 'start': 134, 'end': 141, 'mesh': 'D009530'}, {'text': 'fever', 'type': 'Disease', 'start': 195, 'end': 200, 'mesh': 'D005334'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 205, 'end': 224, 'mesh': 'D058186'}, {'text': 'nicergoline', 'type': 'Chemical', 'start': 263, 'end': 274, 'mesh': 'D009530'}, {'text': 'bendazac lysine', 'type': 'Chemical', 'start': 279, 'end': 294, 'mesh': 'C036067'}, {'text': 'retinal vein occlusion', 'type': 'Disease', 'start': 302, 'end': 324, 'mesh': 'D012170'}, {'text': 'fever', 'type': 'Disease', 'start': 395, 'end': 400, 'mesh': 'D005334'}, {'text': 'skin rash', 'type': 'Disease', 'start': 405, 'end': 414, 'mesh': 'D005076'}, {'text': 'arthralgia', 'type': 'Disease', 'start': 454, 'end': 464, 'mesh': 'D018771'}, {'text': 'fever', 'type': 'Disease', 'start': 469, 'end': 474, 'mesh': 'D005334'}, {'text': 'eosinophilia', 'type': 'Disease', 'start': 506, 'end': 518, 'mesh': 'D004802'}, {'text': 'renal failure', 'type': 'Disease', 'start': 523, 'end': 536, 'mesh': 'D051437'}, {'text': 'AIN', 'type': 'Disease', 'start': 548, 'end': 551, 'mesh': 'D009395'}, {'text': 'nicergoline', 'type': 'Chemical', 'start': 689, 'end': 700, 'mesh': 'D009530'}, {'text': 'nicergoline', 'type': 'Chemical', 'start': 743, 'end': 754, 'mesh': 'D009530'}, {'text': 'methylprednisolone', 'type': 'Chemical', 'start': 771, 'end': 789, 'mesh': 'D008775'}, {'text': 'nicergoline', 'type': 'Chemical', 'start': 886, 'end': 897, 'mesh': 'D009530'}, {'text': 'AIN', 'type': 'Disease', 'start': 909, 'end': 912, 'mesh': 'D009395'}]"
+1366,12452552,Neuroleptic malignant syndrome complicated by massive intestinal bleeding in a patient with chronic renal failure.,"A patient with chronic renal failure (CRF) developed neuroleptic malignant syndrome (NMS) after administration of risperidone and levomepromazine. In addition to the typical symptoms of NMS, massive intestinal bleeding was observed during the episode. This report suggests that NMS in a patient with CRF may be complicated by intestinal bleeding and needs special caution for this complication.","[{'text': 'Neuroleptic malignant syndrome', 'type': 'Disease', 'start': 0, 'end': 30, 'mesh': 'D009459'}, {'text': 'bleeding', 'type': 'Disease', 'start': 65, 'end': 73, 'mesh': 'D006470'}, {'text': 'chronic renal failure', 'type': 'Disease', 'start': 92, 'end': 113, 'mesh': 'D007676'}, {'text': 'chronic renal failure', 'type': 'Disease', 'start': 130, 'end': 151, 'mesh': 'D007676'}, {'text': 'CRF', 'type': 'Disease', 'start': 153, 'end': 156, 'mesh': 'D007676'}, {'text': 'neuroleptic malignant syndrome', 'type': 'Disease', 'start': 168, 'end': 198, 'mesh': 'D009459'}, {'text': 'NMS', 'type': 'Disease', 'start': 200, 'end': 203, 'mesh': 'D009459'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 229, 'end': 240, 'mesh': 'D018967'}, {'text': 'levomepromazine', 'type': 'Chemical', 'start': 245, 'end': 260, 'mesh': 'D008728'}, {'text': 'NMS', 'type': 'Disease', 'start': 301, 'end': 304, 'mesh': 'D009459'}, {'text': 'bleeding', 'type': 'Disease', 'start': 325, 'end': 333, 'mesh': 'D006470'}, {'text': 'NMS', 'type': 'Disease', 'start': 393, 'end': 396, 'mesh': 'D009459'}, {'text': 'CRF', 'type': 'Disease', 'start': 415, 'end': 418, 'mesh': 'D007676'}, {'text': 'bleeding', 'type': 'Disease', 'start': 452, 'end': 460, 'mesh': 'D006470'}]"
+1367,12487093,Blood brain barrier in right- and left-pawed female rats assessed by a new staining method.,"The asymmetrical breakdown of the blood-brain barrier (BBB) was studied in female rats. Paw preference was assessed by a food reaching test. Adrenaline-induced hypertension was used to destroy the BBB, which was evaluated using triphenyltetrazolium (TTC) staining of the brain slices just after giving adrenaline for 30 s. In normal rats, the whole brain sections exhibited complete staining with TTC. After adrenaline infusion for 30 s, there were large unstained areas in the left brain in right-pawed animals, and vice versa in left-pawed animals. Similar results were obtained in seizure-induced breakdown of BBB. These results were explained by an asymmetric cerebral blood flow depending upon the paw preference in rats. It was suggested that this new method and the results are consistent with contralateral motor control that may be important in determining the dominant cerebral hemisphere in animals.","[{'text': 'Adrenaline', 'type': 'Chemical', 'start': 233, 'end': 243, 'mesh': 'D004837'}, {'text': 'hypertension', 'type': 'Disease', 'start': 252, 'end': 264, 'mesh': 'D006973'}, {'text': 'triphenyltetrazolium', 'type': 'Chemical', 'start': 320, 'end': 340, 'mesh': 'C009591'}, {'text': 'TTC', 'type': 'Chemical', 'start': 342, 'end': 345, 'mesh': 'C009591'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 394, 'end': 404, 'mesh': 'D004837'}, {'text': 'TTC', 'type': 'Chemical', 'start': 489, 'end': 492, 'mesh': 'C009591'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 500, 'end': 510, 'mesh': 'D004837'}, {'text': 'seizure', 'type': 'Disease', 'start': 676, 'end': 683, 'mesh': 'D012640'}]"
+1368,12498738,Carvedilol protects against doxorubicin-induced mitochondrial cardiomyopathy.,"Several cytopathic mechanisms have been suggested to mediate the dose-limiting cumulative and irreversible cardiomyopathy caused by doxorubicin. Recent evidence indicates that oxidative stress and mitochondrial dysfunction are key factors in the pathogenic process. The objective of this investigation was to test the hypothesis that carvedilol, a nonselective beta-adrenergic receptor antagonist with potent antioxidant properties, protects against the cardiac and hepatic mitochondrial bioenergetic dysfunction associated with subchronic doxorubicin toxicity. Heart and liver mitochondria were isolated from rats treated for 7 weeks with doxorubicin (2 mg/kg sc/week), carvedilol (1 mg/kg ip/week), or the combination of the two drugs. Heart mitochondria isolated from doxorubicin-treated rats exhibited depressed rates for state 3 respiration (336 +/- 26 versus 425 +/- 53 natom O/min/mg protein) and a lower respiratory control ratio (RCR) (4.3 +/- 0.6 versus 5.8 +/- 0.4) compared with cardiac mitochondria isolated from saline-treated rats. Mitochondrial calcium-loading capacity and the activity of NADH-dehydrogenase were also suppressed in cardiac mitochondria from doxorubicin-treated rats. Doxorubicin treatment also caused a decrease in RCR for liver mitochondria (3.9 +/- 0.9 versus 5.6 +/- 0.7 for control rats) and inhibition of hepatic cytochrome oxidase activity. Coadministration of carvedilol decreased the extent of cellular vacuolization in cardiac myocytes and prevented the inhibitory effect of doxorubicin on mitochondrial respiration in both heart and liver. Carvedilol also prevented the decrease in mitochondrial Ca(2+) loading capacity and the inhibition of the respiratory complexes of heart mitochondria caused by doxorubicin. Carvedilol by itself did not affect any of the parameters measured for heart or liver mitochondria. It is concluded that this protection by carvedilol against both the structural and functional cardiac tissue damage may afford significant clinical advantage in minimizing the dose-limiting mitochondrial dysfunction and cardiomyopathy that accompanies long-term doxorubicin therapy in cancer patients.","[{'text': 'Carvedilol', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'C043211'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 28, 'end': 39, 'mesh': 'D004317'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 62, 'end': 76, 'mesh': 'D009202'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 185, 'end': 199, 'mesh': 'D009202'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 210, 'end': 221, 'mesh': 'D004317'}, {'text': 'mitochondrial dysfunction', 'type': 'Disease', 'start': 275, 'end': 300, 'mesh': 'D028361'}, {'text': 'carvedilol', 'type': 'Chemical', 'start': 412, 'end': 422, 'mesh': 'C043211'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 618, 'end': 629, 'mesh': 'D004317'}, {'text': 'toxicity', 'type': 'Disease', 'start': 630, 'end': 638, 'mesh': 'D064420'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 718, 'end': 729, 'mesh': 'D004317'}, {'text': 'carvedilol', 'type': 'Chemical', 'start': 749, 'end': 759, 'mesh': 'C043211'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 849, 'end': 860, 'mesh': 'D004317'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1139, 'end': 1146, 'mesh': 'D002118'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1253, 'end': 1264, 'mesh': 'D004317'}, {'text': 'Doxorubicin', 'type': 'Chemical', 'start': 1279, 'end': 1290, 'mesh': 'D004317'}, {'text': 'carvedilol', 'type': 'Chemical', 'start': 1479, 'end': 1489, 'mesh': 'C043211'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1596, 'end': 1607, 'mesh': 'D004317'}, {'text': 'Carvedilol', 'type': 'Chemical', 'start': 1662, 'end': 1672, 'mesh': 'C043211'}, {'text': 'Ca', 'type': 'Chemical', 'start': 1718, 'end': 1720, 'mesh': 'D002118'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 1822, 'end': 1833, 'mesh': 'D004317'}, {'text': 'Carvedilol', 'type': 'Chemical', 'start': 1835, 'end': 1845, 'mesh': 'C043211'}, {'text': 'carvedilol', 'type': 'Chemical', 'start': 1975, 'end': 1985, 'mesh': 'C043211'}, {'text': 'mitochondrial dysfunction', 'type': 'Disease', 'start': 2125, 'end': 2150, 'mesh': 'D028361'}, {'text': 'cardiomyopathy', 'type': 'Disease', 'start': 2155, 'end': 2169, 'mesh': 'D009202'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 2197, 'end': 2208, 'mesh': 'D004317'}, {'text': 'cancer', 'type': 'Disease', 'start': 2220, 'end': 2226, 'mesh': 'D009369'}]"
+1369,12523489,Cocaine-induced hyperactivity is more influenced by adenosine receptor agonists than amphetamine-induced hyperactivity.,"The influence of adenosine receptor agonists and antagonists on cocaine-and amphetamine-induced hyperactivity was examined in mice. All adenosine receptor agonists significantly decreased the locomotor activity in mice, and the effects were dose-dependent. It seems that adenosine A1 and A2 receptors might be involved in this reaction. Moreover, all adenosine receptor agonists: 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680), A2A receptor agonist, N6-cyclopentyladenosine (CPA), A1 receptor agonist, and 5'-N-ethylcarboxamidoadenosine (NECA), A2/A1 receptor agonist significantly and dose-dependently decreased cocaine-induced locomotor activity. CPA reduced cocaine action at the doses which, given alone, did not influence motility, while CGS 21680 and NECA decreased the action of cocaine at the doses which, given alone, decreased locomotor activity in animals. These results suggest the involvement of both adenosine receptors in the action of cocaine although agonists of A1 receptors seem to have stronger influence on it. The selective blockade of A2 adenosine receptor by DMPX (3,7-dimethyl-1-propargylxanthine) significantly enhanced cocaine-induced locomotor activity of animals. Caffeine had similar action but the effect was not significant. CPT (8-cyclopentyltheophylline)--A1 receptor antagonist, did not show any influence in this test. Similarly, all adenosine receptor agonists decreased amphetamine-induced hyperactivity, but at the higher doses than those which were active in cocaine-induced hyperactivity. The selective blockade of A2 adenosine receptors (DMPX) and non-selective blockade of adenosine receptors (caffeine) significantly increased the action of amphetamine in the locomotor activity test. Our results have shown that all adenosine receptor agonists (A1 and A2) reduce cocaine- and amphetamine-induced locomotor activity and indicate that cocaine-induced hyperactivity is more influenced by adenosine receptor agonists (particularly A1 receptors) than amphetamine-induced hyperactivity.","[{'text': 'Cocaine', 'type': 'Chemical', 'start': 0, 'end': 7, 'mesh': 'D003042'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 16, 'end': 29, 'mesh': 'D006948'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 52, 'end': 61, 'mesh': 'D000241'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 85, 'end': 96, 'mesh': 'D000661'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 105, 'end': 118, 'mesh': 'D006948'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 137, 'end': 146, 'mesh': 'D000241'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 184, 'end': 191, 'mesh': 'D003042'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 196, 'end': 207, 'mesh': 'D000661'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 216, 'end': 229, 'mesh': 'D006948'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 256, 'end': 265, 'mesh': 'D000241'}, {'text': 'decreased the locomotor activity', 'type': 'Disease', 'start': 298, 'end': 330, 'mesh': 'D004409'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 391, 'end': 400, 'mesh': 'D000241'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 471, 'end': 480, 'mesh': 'D000241'}, {'text': ""2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine"", 'type': 'Chemical', 'start': 500, 'end': 565, 'mesh': 'C061282'}, {'text': 'CGS 21680', 'type': 'Chemical', 'start': 567, 'end': 576, 'mesh': 'C061282'}, {'text': 'N6-cyclopentyladenosine', 'type': 'Chemical', 'start': 601, 'end': 624, 'mesh': 'C048599'}, {'text': 'CPA', 'type': 'Chemical', 'start': 626, 'end': 629, 'mesh': 'C048599'}, {'text': ""5'-N-ethylcarboxamidoadenosine"", 'type': 'Chemical', 'start': 657, 'end': 687, 'mesh': 'D019830'}, {'text': 'NECA', 'type': 'Chemical', 'start': 689, 'end': 693, 'mesh': 'D019830'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 764, 'end': 771, 'mesh': 'D003042'}, {'text': 'CPA', 'type': 'Chemical', 'start': 800, 'end': 803, 'mesh': 'C048599'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 812, 'end': 819, 'mesh': 'D003042'}, {'text': 'CGS 21680', 'type': 'Chemical', 'start': 894, 'end': 903, 'mesh': 'C061282'}, {'text': 'NECA', 'type': 'Chemical', 'start': 908, 'end': 912, 'mesh': 'D019830'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 937, 'end': 944, 'mesh': 'D003042'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 1065, 'end': 1074, 'mesh': 'D000241'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1102, 'end': 1109, 'mesh': 'D003042'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 1212, 'end': 1221, 'mesh': 'D000241'}, {'text': 'DMPX', 'type': 'Chemical', 'start': 1234, 'end': 1238, 'mesh': 'C057837'}, {'text': '3,7-dimethyl-1-propargylxanthine', 'type': 'Chemical', 'start': 1240, 'end': 1272, 'mesh': 'C057837'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1297, 'end': 1304, 'mesh': 'D003042'}, {'text': 'Caffeine', 'type': 'Chemical', 'start': 1344, 'end': 1352, 'mesh': 'D002110'}, {'text': 'CPT', 'type': 'Chemical', 'start': 1408, 'end': 1411, 'mesh': 'C053907'}, {'text': '8-cyclopentyltheophylline', 'type': 'Chemical', 'start': 1413, 'end': 1438, 'mesh': 'C053907'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 1521, 'end': 1530, 'mesh': 'D000241'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1559, 'end': 1570, 'mesh': 'D000661'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 1579, 'end': 1592, 'mesh': 'D006948'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1650, 'end': 1657, 'mesh': 'D003042'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 1666, 'end': 1679, 'mesh': 'D006948'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 1710, 'end': 1719, 'mesh': 'D000241'}, {'text': 'DMPX', 'type': 'Chemical', 'start': 1731, 'end': 1735, 'mesh': 'C057837'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 1767, 'end': 1776, 'mesh': 'D000241'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1788, 'end': 1796, 'mesh': 'D002110'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1836, 'end': 1847, 'mesh': 'D000661'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 1912, 'end': 1921, 'mesh': 'D000241'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1959, 'end': 1966, 'mesh': 'D003042'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 1972, 'end': 1983, 'mesh': 'D000661'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 2029, 'end': 2036, 'mesh': 'D003042'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 2045, 'end': 2058, 'mesh': 'D006948'}, {'text': 'adenosine', 'type': 'Chemical', 'start': 2081, 'end': 2090, 'mesh': 'D000241'}, {'text': 'amphetamine', 'type': 'Chemical', 'start': 2142, 'end': 2153, 'mesh': 'D000661'}, {'text': 'hyperactivity', 'type': 'Disease', 'start': 2162, 'end': 2175, 'mesh': 'D006948'}]"
+1370,12535818,Amiodarone and the risk of bradyarrhythmia requiring permanent pacemaker in elderly patients with atrial fibrillation and prior myocardial infarction.,"OBJECTIVES: The aim of this study was to determine whether the use of amiodarone in patients with atrial fibrillation (AF) increases the risk of bradyarrhythmia requiring a permanent pacemaker. BACKGROUND: Reports of severe bradyarrhythmia during amiodarone therapy are infrequent and limited to studies assessing the therapy's use in the management of patients with ventricular arrhythmias. METHODS: A study cohort of 8,770 patients age > or =65 years with a new diagnosis of AF was identified from a provincewide database of Quebec residents with a myocardial infarction (MI) between 1991 and 1999. Using a nested case-control design, 477 cases of bradyarrhythmia requiring a permanent pacemaker were matched (1:4) to 1,908 controls. Multivariable logistic regression was used to estimate the odds ratio (OR) of pacemaker insertion associated with amiodarone use, controlling for baseline risk factors and exposure to sotalol, Class I antiarrhythmic agents, beta-blockers, calcium channel blockers, and digoxin. RESULTS: amiodarone use was associated with an increased risk of pacemaker insertion (OR: 2.14, 95% confidence interval [CI]: 1.30 to 3.54). This effect was modified by gender, with a greater risk in women versus men (OR: 3.86, 95% CI: 1.70 to 8.75 vs. OR: 1.52, 95% CI: 0.80 to 2.89). Digoxin was the only other medication associated with an increased risk of pacemaker insertion (OR: 1.78, 95% CI: 1.37 to 2.31). CONCLUSIONS: This study suggests that the use of amiodarone in elderly patients with AF and a previous MI increases the risk of bradyarrhythmia requiring a permanent pacemaker. The finding of an augmented risk of pacemaker insertion in elderly women receiving amiodarone requires further investigation.","[{'text': 'Amiodarone', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D000638'}, {'text': 'bradyarrhythmia', 'type': 'Disease', 'start': 27, 'end': 42, 'mesh': 'D001919'}, {'text': 'atrial fibrillation', 'type': 'Disease', 'start': 98, 'end': 117, 'mesh': 'D001281'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 128, 'end': 149, 'mesh': 'D009203'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 221, 'end': 231, 'mesh': 'D000638'}, {'text': 'atrial fibrillation', 'type': 'Disease', 'start': 249, 'end': 268, 'mesh': 'D001281'}, {'text': 'AF', 'type': 'Disease', 'start': 270, 'end': 272, 'mesh': 'D001281'}, {'text': 'bradyarrhythmia', 'type': 'Disease', 'start': 296, 'end': 311, 'mesh': 'D001919'}, {'text': 'bradyarrhythmia', 'type': 'Disease', 'start': 375, 'end': 390, 'mesh': 'D001919'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 398, 'end': 408, 'mesh': 'D000638'}, {'text': 'ventricular arrhythmias', 'type': 'Disease', 'start': 518, 'end': 541, 'mesh': 'D001145'}, {'text': 'AF', 'type': 'Disease', 'start': 628, 'end': 630, 'mesh': 'D001281'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 702, 'end': 723, 'mesh': 'D009203'}, {'text': 'MI', 'type': 'Disease', 'start': 725, 'end': 727, 'mesh': 'D009203'}, {'text': 'bradyarrhythmia', 'type': 'Disease', 'start': 801, 'end': 816, 'mesh': 'D001919'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 1001, 'end': 1011, 'mesh': 'D000638'}, {'text': 'sotalol', 'type': 'Chemical', 'start': 1071, 'end': 1078, 'mesh': 'D013015'}, {'text': 'calcium', 'type': 'Chemical', 'start': 1126, 'end': 1133, 'mesh': 'D002118'}, {'text': 'digoxin', 'type': 'Chemical', 'start': 1156, 'end': 1163, 'mesh': 'D004077'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 1174, 'end': 1184, 'mesh': 'D000638'}, {'text': 'Digoxin', 'type': 'Chemical', 'start': 1451, 'end': 1458, 'mesh': 'D004077'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 1629, 'end': 1639, 'mesh': 'D000638'}, {'text': 'AF', 'type': 'Disease', 'start': 1665, 'end': 1667, 'mesh': 'D001281'}, {'text': 'MI', 'type': 'Disease', 'start': 1683, 'end': 1685, 'mesh': 'D009203'}, {'text': 'bradyarrhythmia', 'type': 'Disease', 'start': 1708, 'end': 1723, 'mesh': 'D001919'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 1840, 'end': 1850, 'mesh': 'D000638'}]"
+1371,12559315,Indomethacin-induced morphologic changes in the rat urinary bladder epithelium.,"OBJECTIVES: To evaluate the morphologic changes in rat urothelium induced by indomethacin. Nonsteroidal anti-inflammatory drug-induced cystitis is a poorly recognized and under-reported condition. In addition to tiaprofenic acid, indomethacin has been reported to be associated with this condition. METHODS: Three groups were established: a control group (n = 10), a high-dose group (n = 10), treated with one intraperitoneal injection of indomethacin 20 mg/kg, and a therapeutic dose group (n = 10) in which oral indomethacin was administered 3.25 mg/kg body weight daily for 3 weeks. The animals were then killed and the bladders removed for light and electron microscopic studies. RESULTS: The light microscopic findings showed some focal epithelial degeneration that was more prominent in the high-dose group. When compared with the control group, both indomethacin groups revealed statistically increased numbers of mast cells in the mucosa (P <0.0001) and penetration of lanthanum nitrate through intercellular areas of the epithelium. Furthermore, the difference in mast cell counts between the high and therapeutic dose groups was also statistically significant (P <0.0001). CONCLUSIONS: Indomethacin resulted in histopathologic findings typical of interstitial cystitis, such as leaky bladder epithelium and mucosal mastocytosis. The true incidence of nonsteroidal anti-inflammatory drug-induced cystitis in humans must be clarified by prospective clinical trials.","[{'text': 'Indomethacin', 'type': 'Chemical', 'start': 0, 'end': 12, 'mesh': 'D007213'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 157, 'end': 169, 'mesh': 'D007213'}, {'text': 'cystitis', 'type': 'Disease', 'start': 215, 'end': 223, 'mesh': 'D003556'}, {'text': 'tiaprofenic acid', 'type': 'Chemical', 'start': 292, 'end': 308, 'mesh': 'C021270'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 310, 'end': 322, 'mesh': 'D007213'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 519, 'end': 531, 'mesh': 'D007213'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 594, 'end': 606, 'mesh': 'D007213'}, {'text': 'indomethacin', 'type': 'Chemical', 'start': 937, 'end': 949, 'mesh': 'D007213'}, {'text': 'lanthanum nitrate', 'type': 'Chemical', 'start': 1057, 'end': 1074, 'mesh': 'C016534'}, {'text': 'Indomethacin', 'type': 'Chemical', 'start': 1276, 'end': 1288, 'mesh': 'D007213'}, {'text': 'interstitial cystitis', 'type': 'Disease', 'start': 1337, 'end': 1358, 'mesh': 'D018856'}, {'text': 'mastocytosis', 'type': 'Disease', 'start': 1405, 'end': 1417, 'mesh': 'D008415'}, {'text': 'cystitis', 'type': 'Disease', 'start': 1485, 'end': 1493, 'mesh': 'D003556'}]"
+1372,12644816,An open-label phase II study of low-dose thalidomide in androgen-independent prostate cancer.,"The antiangiogenic effects of thalidomide have been assessed in clinical trials in patients with various solid and haematological malignancies. Thalidomide blocks the activity of angiogenic agents including bFGF, VEGF and IL-6. We undertook an open-label study using thalidomide 100 mg once daily for up to 6 months in 20 men with androgen-independent prostate cancer. The mean time of study was 109 days (median 107, range 4-184 days). Patients underwent regular measurement of prostate-specific antigen (PSA), urea and electrolytes, serum bFGF and VEGF. Three men (15%) showed a decline in serum PSA of at least 50%, sustained throughout treatment. Of 16 men treated for at least 2 months, six (37.5%) showed a fall in absolute PSA by a median of 48%. Increasing levels of serum bFGF and VEGF were associated with progressive disease; five of six men who demonstrated a fall in PSA also showed a decline in bFGF and VEGF levels, and three of four men with a rising PSA showed an increase in both growth factors. Adverse effects included constipation, morning drowsiness, dizziness and rash, and resulted in withdrawal from the study by three men. Evidence of peripheral sensory neuropathy was found in nine of 13 men before treatment. In the seven men who completed six months on thalidomide, subclinical evidence of peripheral neuropathy was found in four before treatment, but in all seven at repeat testing. The findings indicate that thalidomide may be an option for patients who have failed other forms of therapy, provided close follow-up is maintained for development of peripheral neuropathy.","[{'text': 'thalidomide', 'type': 'Chemical', 'start': 41, 'end': 52, 'mesh': 'D013792'}, {'text': 'androgen', 'type': 'Chemical', 'start': 56, 'end': 64, 'mesh': 'D000728'}, {'text': 'prostate cancer', 'type': 'Disease', 'start': 77, 'end': 92, 'mesh': 'D011471'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 124, 'end': 135, 'mesh': 'D013792'}, {'text': 'haematological malignancies', 'type': 'Disease', 'start': 209, 'end': 236, 'mesh': 'D019337'}, {'text': 'Thalidomide', 'type': 'Chemical', 'start': 238, 'end': 249, 'mesh': 'D013792'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 361, 'end': 372, 'mesh': 'D013792'}, {'text': 'androgen', 'type': 'Chemical', 'start': 425, 'end': 433, 'mesh': 'D000728'}, {'text': 'prostate cancer', 'type': 'Disease', 'start': 446, 'end': 461, 'mesh': 'D011471'}, {'text': 'urea', 'type': 'Chemical', 'start': 606, 'end': 610, 'mesh': 'D014508'}, {'text': 'constipation', 'type': 'Disease', 'start': 1133, 'end': 1145, 'mesh': 'D003248'}, {'text': 'drowsiness', 'type': 'Disease', 'start': 1155, 'end': 1165, 'mesh': 'D006970'}, {'text': 'dizziness', 'type': 'Disease', 'start': 1167, 'end': 1176, 'mesh': 'D004244'}, {'text': 'rash', 'type': 'Disease', 'start': 1181, 'end': 1185, 'mesh': 'D005076'}, {'text': 'peripheral sensory neuropathy', 'type': 'Disease', 'start': 1255, 'end': 1284, 'mesh': 'D010523'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 1376, 'end': 1387, 'mesh': 'D013792'}, {'text': 'peripheral neuropathy', 'type': 'Disease', 'start': 1413, 'end': 1434, 'mesh': 'D010523'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 1534, 'end': 1545, 'mesh': 'D013792'}, {'text': 'peripheral neuropathy', 'type': 'Disease', 'start': 1674, 'end': 1695, 'mesh': 'D010523'}]"
+1373,12677626,Central nervous system toxicity following the administration of levobupivacaine for lumbar plexus block: A report of two cases.,"BACKGROUND AND OBJECTIVES: Central nervous system and cardiac toxicity following the administration of local anesthetics is a recognized complication of regional anesthesia. Levobupivacaine, the pure S(-) enantiomer of bupivacaine, was developed to improve the cardiac safety profile of bupivacaine. We describe 2 cases of grand mal seizures following accidental intravascular injection of levobupivacaine. CASE REPORT: Two patients presenting for elective orthopedic surgery of the lower limb underwent blockade of the lumbar plexus via the posterior approach. Immediately after the administration of levobupivacaine 0.5% with epinephrine 2.5 microgram/mL, the patients developed grand mal seizures, despite negative aspiration for blood and no clinical signs of intravenous epinephrine administration. The seizures were successfully treated with sodium thiopental in addition to succinylcholine in 1 patient. Neither patient developed signs of cardiovascular toxicity. Both patients were treated preoperatively with beta-adrenergic antagonist medications, which may have masked the cardiovascular signs of the unintentional intravascular administration of levobupivacaine with epinephrine. CONCLUSIONS: Although levobupivacaine may have a safer cardiac toxicity profile than racemic bupivacaine, if adequate amounts of levobupivacaine reach the circulation, it will result in convulsions. Plasma concentrations sufficient to result in central nervous system toxicity did not produce manifestations of cardiac toxicity in these 2 patients.","[{'text': 'Central nervous system toxicity', 'type': 'Disease', 'start': 0, 'end': 31, 'mesh': 'D020258'}, {'text': 'levobupivacaine', 'type': 'Chemical', 'start': 64, 'end': 79, 'mesh': 'C476513'}, {'text': 'Levobupivacaine', 'type': 'Chemical', 'start': 302, 'end': 317, 'mesh': 'C476513'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 347, 'end': 358, 'mesh': 'D002045'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 415, 'end': 426, 'mesh': 'D002045'}, {'text': 'grand mal seizures', 'type': 'Disease', 'start': 451, 'end': 469, 'mesh': 'D004830'}, {'text': 'levobupivacaine', 'type': 'Chemical', 'start': 518, 'end': 533, 'mesh': 'C476513'}, {'text': 'levobupivacaine', 'type': 'Chemical', 'start': 730, 'end': 745, 'mesh': 'C476513'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 756, 'end': 767, 'mesh': 'D004837'}, {'text': 'grand mal seizures', 'type': 'Disease', 'start': 809, 'end': 827, 'mesh': 'D004830'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 904, 'end': 915, 'mesh': 'D004837'}, {'text': 'seizures', 'type': 'Disease', 'start': 936, 'end': 944, 'mesh': 'D012640'}, {'text': 'sodium thiopental', 'type': 'Chemical', 'start': 976, 'end': 993, 'mesh': 'D013874'}, {'text': 'succinylcholine', 'type': 'Chemical', 'start': 1009, 'end': 1024, 'mesh': 'D013390'}, {'text': 'cardiovascular toxicity', 'type': 'Disease', 'start': 1074, 'end': 1097, 'mesh': 'D002318'}, {'text': 'levobupivacaine', 'type': 'Chemical', 'start': 1286, 'end': 1301, 'mesh': 'C476513'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 1307, 'end': 1318, 'mesh': 'D004837'}, {'text': 'levobupivacaine', 'type': 'Chemical', 'start': 1342, 'end': 1357, 'mesh': 'C476513'}, {'text': 'cardiac toxicity', 'type': 'Disease', 'start': 1375, 'end': 1391, 'mesh': 'D066126'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 1413, 'end': 1424, 'mesh': 'D002045'}, {'text': 'levobupivacaine', 'type': 'Chemical', 'start': 1449, 'end': 1464, 'mesh': 'C476513'}, {'text': 'convulsions', 'type': 'Disease', 'start': 1506, 'end': 1517, 'mesh': 'D012640'}, {'text': 'central nervous system toxicity', 'type': 'Disease', 'start': 1565, 'end': 1596, 'mesh': 'D020258'}, {'text': 'cardiac toxicity', 'type': 'Disease', 'start': 1631, 'end': 1647, 'mesh': 'D066126'}]"
+1374,12699527,Anaesthetic complications associated with myotonia congenita: case study and comparison with other myotonic disorders.,"Myotonia congenita (MC) is caused by a defect in the skeletal muscle chloride channel function, which may cause sustained membrane depolarisation. We describe a previously healthy 32-year-old woman who developed a life-threatening muscle spasm and secondary ventilation difficulties following a preoperative injection of suxamethonium. The muscle spasms disappeared spontaneously and the surgery proceeded without further problems. When subsequently questioned, she reported minor symptoms suggesting a myotonic condition. Myotonia was found on clinical examination and EMG. The diagnosis MC was confirmed genetically. Neither the patient nor the anaesthetist were aware of the diagnosis before this potentially lethal complication occurred. We give a brief overview of ion channel disorders including malignant hyperthermia and their anaesthetic considerations.","[{'text': 'myotonia congenita', 'type': 'Disease', 'start': 42, 'end': 60, 'mesh': 'D009224'}, {'text': 'myotonic disorders', 'type': 'Disease', 'start': 99, 'end': 117, 'mesh': 'D020967'}, {'text': 'Myotonia congenita', 'type': 'Disease', 'start': 119, 'end': 137, 'mesh': 'D009224'}, {'text': 'MC', 'type': 'Disease', 'start': 139, 'end': 141, 'mesh': 'D009224'}, {'text': 'chloride', 'type': 'Chemical', 'start': 188, 'end': 196, 'mesh': 'D002712'}, {'text': 'sustained membrane depolarisation', 'type': 'Disease', 'start': 231, 'end': 264, 'mesh': '-1'}, {'text': 'muscle spasm', 'type': 'Disease', 'start': 350, 'end': 362, 'mesh': 'D013035'}, {'text': 'suxamethonium', 'type': 'Chemical', 'start': 440, 'end': 453, 'mesh': 'D013390'}, {'text': 'muscle spasms', 'type': 'Disease', 'start': 459, 'end': 472, 'mesh': 'D013035'}, {'text': 'myotonic condition', 'type': 'Disease', 'start': 622, 'end': 640, 'mesh': 'D020967'}, {'text': 'Myotonia', 'type': 'Disease', 'start': 642, 'end': 650, 'mesh': 'D009222'}, {'text': 'MC', 'type': 'Disease', 'start': 708, 'end': 710, 'mesh': 'D009224'}, {'text': 'ion channel disorders', 'type': 'Disease', 'start': 889, 'end': 910, 'mesh': '-1'}, {'text': 'malignant hyperthermia', 'type': 'Disease', 'start': 921, 'end': 943, 'mesh': 'D008305'}]"
+1375,12752472,Respiratory pattern in a rat model of epilepsy.,"PURPOSE: Apnea is known to occur during seizures, but systematic studies of ictal respiratory changes in adults are few. Data regarding respiratory pattern defects during interictal periods also are scarce. Here we sought to generate information with regard to the interictal period in animals with pilocarpine-induced epilepsy. METHODS: Twelve rats (six chronically epileptic animals and six controls) were anesthetized, given tracheotomies, and subjected to hyperventilation or hypoventilation conditions. Breathing movements caused changes in thoracic volume and forced air to flow tidally through a pneumotachograph. This flow was measured by using a differential pressure transducer, passed through a polygraph, and from this to a computer with custom software that derived ventilation (VE), tidal volume (VT), inspiratory time (TI), expiratory time (TE), breathing frequency (f), and mean inspiratory flow (VT/TI) on a breath-by-breath basis. RESULTS: The hyperventilation maneuver caused a decrease in spontaneous ventilation in pilocarpine-treated and control rats. Although VE had a similar decrease in both groups, in the epileptic group, the decrease in VE was due to a significant (p < 0.05) increase in TE peak in relation to that of the control animals. The hypoventilation maneuver led to an increase in the arterial Paco2, followed by an increase in VE. In the epileptic group, the increase in VE was mediated by a significant (p < 0.05) decrease in TE peak compared with the control group. Systemic application of KCN, to evaluate the effects of peripheral chemoreception activation on ventilation, led to a similar increase in VE for both groups. CONCLUSIONS: The data indicate that pilocarpine-treated animals have an altered ability to react to (or compensate for) blood gas changes with changes in ventilation and suggest that it is centrally determined. We speculate on the possible relation of the current findings on treating different epilepsy-associated conditions.","[{'text': 'epilepsy', 'type': 'Disease', 'start': 38, 'end': 46, 'mesh': 'D004827'}, {'text': 'Apnea', 'type': 'Disease', 'start': 57, 'end': 62, 'mesh': 'D001049'}, {'text': 'seizures', 'type': 'Disease', 'start': 88, 'end': 96, 'mesh': 'D012640'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 347, 'end': 358, 'mesh': 'D010862'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 367, 'end': 375, 'mesh': 'D004827'}, {'text': 'epileptic', 'type': 'Disease', 'start': 415, 'end': 424, 'mesh': 'D004827'}, {'text': 'hyperventilation', 'type': 'Disease', 'start': 508, 'end': 524, 'mesh': 'D006985'}, {'text': 'hyperventilation', 'type': 'Disease', 'start': 1010, 'end': 1026, 'mesh': 'D006985'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1084, 'end': 1095, 'mesh': 'D010862'}, {'text': 'epileptic', 'type': 'Disease', 'start': 1180, 'end': 1189, 'mesh': 'D004827'}, {'text': 'epileptic', 'type': 'Disease', 'start': 1425, 'end': 1434, 'mesh': 'D004827'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1749, 'end': 1760, 'mesh': 'D010862'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 2008, 'end': 2016, 'mesh': 'D004827'}]"
+1376,12828076,Increased serum soluble Fas in patients with acute liver failure due to paracetamol overdose.,"BACKGROUND/AIMS: Experimental studies have suggested that apoptosis via the Fas/Fas Ligand signaling system may play an important role in the development of acute liver failure. The aim of the study was to investigate the soluble form of Fas in patients with acute liver failure. METHODOLOGY: Serum levels of sFas (soluble Fas) were measured by ELISA in 24 patients with acute liver failure and 10 normal control subjects. Serum levels of tumor necrosis factor-alpha and interferon-gamma were also determined by ELISA. RESULTS: Serum sFas was significantly increased in patients with acute liver failure (median, 26.8 U/mL; range, 6.9-52.7 U/mL) compared to the normal controls (median, 8.6 U/mL; range, 6.5-12.0 U/mL, P < 0.0001). Levels were significantly greater in patients with acute liver failure due to paracetamol overdose (median, 28.7 U/mL; range, 12.8-52.7 U/mL, n = 17) than those due to non-A to E hepatitis (median, 12.5 U/mL; range, 6.9-46.0 U/mL, n = 7, P < 0.01). There was no relationship of sFas to eventual outcome in the patients. A significant correlation was observed between serum sFas levels and aspartate aminotransferase (r = 0.613, P < 0.01). CONCLUSIONS: The increased concentration of sFas in serum of patients with acute liver failure may reflect activation of Fas-mediated apoptosis in the liver and this together with increased tumor necrosis factor-alpha may be an important factor in liver cell loss.","[{'text': 'acute liver failure', 'type': 'Disease', 'start': 45, 'end': 64, 'mesh': 'D017114'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 72, 'end': 83, 'mesh': 'D000082'}, {'text': 'overdose', 'type': 'Disease', 'start': 84, 'end': 92, 'mesh': 'D062787'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 251, 'end': 270, 'mesh': 'D017114'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 353, 'end': 372, 'mesh': 'D017114'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 465, 'end': 484, 'mesh': 'D017114'}, {'text': 'tumor', 'type': 'Disease', 'start': 533, 'end': 538, 'mesh': 'D009369'}, {'text': 'necrosis', 'type': 'Disease', 'start': 539, 'end': 547, 'mesh': 'D009336'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 678, 'end': 697, 'mesh': 'D017114'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 877, 'end': 896, 'mesh': 'D017114'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 904, 'end': 915, 'mesh': 'D000082'}, {'text': 'overdose', 'type': 'Disease', 'start': 916, 'end': 924, 'mesh': 'D062787'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 1005, 'end': 1014, 'mesh': 'D056486'}, {'text': 'aspartate', 'type': 'Chemical', 'start': 1215, 'end': 1224, 'mesh': 'D001224'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 1340, 'end': 1359, 'mesh': 'D017114'}, {'text': 'tumor', 'type': 'Disease', 'start': 1455, 'end': 1460, 'mesh': 'D009369'}, {'text': 'necrosis', 'type': 'Disease', 'start': 1461, 'end': 1469, 'mesh': 'D009336'}]"
+1377,12865514,Bilateral subthalamic nucleus stimulation for Parkinson's disease.,"High frequency stimulation of the subthalamic nucleus (STN) is known to ameliorate the signs and symptoms of advanced Parkinson's disease. AIM: We studied the effect of high frequency STN stimulation in 23 patients. METHOD: Twenty-three patients suffering from severe Parkinson's disease (Stages III-V on Hoehn and Yahr scale) and, particularly bradykinesia, rigidity, and levodopa-induced dyskinesias underwent bilateral implantation of electrodes in the STN. Preoperative and postoperative assessments of these patients at 1, 3, 6 and 12 months follow-up, in ""on"" and ""off"" drug conditions, was carried out using Unified Parkinson's Disease Rating Scale, Hoehn and Yahr staging, England activities of daily living score and video recordings. RESULTS: After one year of electrical stimulation of the STN, the patients' scores for activities of daily living and motor examination scores (Unified Parkinson's Disease Rating Scale parts II and III) off medication improved by 62% and 61% respectively (p<0.0005). The subscores for the akinesia, rigidity, tremor and gait also improved. (p<0.0005). The average levodopa dose decreased from 813 mg to 359 mg. The cognitive functions remained unchanged. Two patients developed device-related complications and two patients experienced abnormal weight gain. CONCLUSION: Bilateral subthalamic nucleus stimulation is an effective treatment for advanced Parkinson's disease. It reduces the severity of ""off"" phase symptoms, improves the axial symptoms and reduces levodopa requirements. The reduction in the levodopa dose is useful in controlling drug-induced dyskinesias.","[{'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 46, 'end': 65, 'mesh': 'D010300'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 185, 'end': 204, 'mesh': 'D010300'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 335, 'end': 354, 'mesh': 'D010300'}, {'text': 'bradykinesia', 'type': 'Disease', 'start': 412, 'end': 424, 'mesh': 'D018476'}, {'text': 'rigidity', 'type': 'Disease', 'start': 426, 'end': 434, 'mesh': 'D009127'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 440, 'end': 448, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 457, 'end': 468, 'mesh': 'D004409'}, {'text': ""Parkinson's Disease"", 'type': 'Disease', 'start': 690, 'end': 709, 'mesh': 'D010300'}, {'text': ""Parkinson's Disease"", 'type': 'Disease', 'start': 963, 'end': 982, 'mesh': 'D010300'}, {'text': 'akinesia', 'type': 'Disease', 'start': 1100, 'end': 1108, 'mesh': 'D004409'}, {'text': 'rigidity', 'type': 'Disease', 'start': 1110, 'end': 1118, 'mesh': 'D009127'}, {'text': 'tremor', 'type': 'Disease', 'start': 1120, 'end': 1126, 'mesh': 'D014202'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1175, 'end': 1183, 'mesh': 'D007980'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 1462, 'end': 1481, 'mesh': 'D010300'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1572, 'end': 1580, 'mesh': 'D007980'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1616, 'end': 1624, 'mesh': 'D007980'}, {'text': 'drug-induced dyskinesias', 'type': 'Disease', 'start': 1655, 'end': 1679, 'mesh': 'D004409'}]"
+1378,12912689,Ocular motility changes after subtenon carboplatin chemotherapy for retinoblastoma.,"BACKGROUND: Focal subtenon carboplatin injections have recently been used as a presumably toxicity-free adjunct to systemic chemotherapy for intraocular retinoblastoma. OBJECTIVE: To report our clinical experience with abnormal ocular motility in patients treated with subtenon carboplatin chemotherapy. METHODS: We noted abnormal ocular motility in 10 consecutive patients with retinoblastoma who had received subtenon carboplatin. During ocular manipulation under general anesthesia, we assessed their eyes by forced duction testing, comparing ocular motility after tumor control with ocular motility at diagnosis. Eyes subsequently enucleated because of treatment failure (n = 4) were examined histologically. RESULTS: Limitation of ocular motility was detected in all 12 eyes of 10 patients treated for intraocular retinoblastoma with 1 to 6 injections of subtenon carboplatin as part of multimodality therapy. Histopathological examination revealed many lipophages in the periorbital fat surrounding the optic nerve in 1 eye, indicative of phagocytosis of previously existing fat cells and suggesting prior fat necrosis. The enucleations were technically difficult and hazardous for globe rupture because of extensive orbital soft tissue adhesions. CONCLUSIONS: Subtenon carboplatin chemotherapy is associated with significant fibrosis of orbital soft tissues, leading to mechanical restriction of eye movements and making subsequent enucleation difficult. Subtenon carboplatin is not free of toxicity, and its use is best restricted to specific indications.","[{'text': 'carboplatin', 'type': 'Chemical', 'start': 39, 'end': 50, 'mesh': 'D016190'}, {'text': 'retinoblastoma', 'type': 'Disease', 'start': 68, 'end': 82, 'mesh': 'D012175'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 111, 'end': 122, 'mesh': 'D016190'}, {'text': 'toxicity', 'type': 'Disease', 'start': 174, 'end': 182, 'mesh': 'D064420'}, {'text': 'retinoblastoma', 'type': 'Disease', 'start': 237, 'end': 251, 'mesh': 'D012175'}, {'text': 'abnormal ocular motility', 'type': 'Disease', 'start': 303, 'end': 327, 'mesh': 'D015835'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 362, 'end': 373, 'mesh': 'D016190'}, {'text': 'abnormal ocular motility', 'type': 'Disease', 'start': 406, 'end': 430, 'mesh': 'D015835'}, {'text': 'retinoblastoma', 'type': 'Disease', 'start': 463, 'end': 477, 'mesh': 'D012175'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 504, 'end': 515, 'mesh': 'D016190'}, {'text': 'tumor', 'type': 'Disease', 'start': 652, 'end': 657, 'mesh': 'D009369'}, {'text': 'retinoblastoma', 'type': 'Disease', 'start': 903, 'end': 917, 'mesh': 'D012175'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 953, 'end': 964, 'mesh': 'D016190'}, {'text': 'necrosis', 'type': 'Disease', 'start': 1200, 'end': 1208, 'mesh': 'D009336'}, {'text': 'rupture', 'type': 'Disease', 'start': 1278, 'end': 1285, 'mesh': 'D012421'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 1360, 'end': 1371, 'mesh': 'D016190'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 1416, 'end': 1424, 'mesh': 'D005355'}, {'text': 'carboplatin', 'type': 'Chemical', 'start': 1555, 'end': 1566, 'mesh': 'D016190'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1582, 'end': 1590, 'mesh': 'D064420'}]"
+1379,12948256,Ethambutol and optic neuropathy.,"PURPOSE: To demonstrate the association between ethambutol and optic neuropathy. METHOD: Thirteen patients who developed optic neuropathy after being treated with ethambutol for tuberculosis of the lung or lymph node at Siriraj Hospital between 1997 and 2001 were retrospectively reviewed. The clinical characteristics and initial and final visual acuity were analyzed to determine visual outcome. RESULTS: All patients had optic neuropathy between 1 to 6 months (mean = 2.9 months) after starting ethambutol therapy at a dosage ranging from 13 to 20 mg/kg/day (mean = 17 mg/kg/day). Seven (54%) of the 13 patients experienced visual recovery after stopping the drug. Of 6 patients with irreversible visual impairment, 4 patients had diabetes mellitus, glaucoma and a history of heavy smoking. CONCLUSION: Early recognition of optic neuropathy should be considered in patients with ethambutol therapy. A low dose and prompt discontinuation of the drug is recommended particularly in individuals with diabetes mellitus, glaucoma or who are heavy smokers.","[{'text': 'Ethambutol', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D004977'}, {'text': 'optic neuropathy', 'type': 'Disease', 'start': 15, 'end': 31, 'mesh': 'D009901'}, {'text': 'ethambutol', 'type': 'Chemical', 'start': 81, 'end': 91, 'mesh': 'D004977'}, {'text': 'optic neuropathy', 'type': 'Disease', 'start': 96, 'end': 112, 'mesh': 'D009901'}, {'text': 'optic neuropathy', 'type': 'Disease', 'start': 154, 'end': 170, 'mesh': 'D009901'}, {'text': 'ethambutol', 'type': 'Chemical', 'start': 196, 'end': 206, 'mesh': 'D004977'}, {'text': 'optic neuropathy', 'type': 'Disease', 'start': 457, 'end': 473, 'mesh': 'D009901'}, {'text': 'ethambutol', 'type': 'Chemical', 'start': 531, 'end': 541, 'mesh': 'D004977'}, {'text': 'visual impairment', 'type': 'Disease', 'start': 733, 'end': 750, 'mesh': 'D014786'}, {'text': 'diabetes mellitus', 'type': 'Disease', 'start': 767, 'end': 784, 'mesh': 'D003920'}, {'text': 'glaucoma', 'type': 'Disease', 'start': 786, 'end': 794, 'mesh': 'D005901'}, {'text': 'optic neuropathy', 'type': 'Disease', 'start': 860, 'end': 876, 'mesh': 'D009901'}, {'text': 'ethambutol', 'type': 'Chemical', 'start': 915, 'end': 925, 'mesh': 'D004977'}, {'text': 'diabetes mellitus', 'type': 'Disease', 'start': 1033, 'end': 1050, 'mesh': 'D003920'}, {'text': 'glaucoma', 'type': 'Disease', 'start': 1052, 'end': 1060, 'mesh': 'D005901'}]"
+1380,12950111,Treatment of compensatory gustatory hyperhidrosis with topical glycopyrrolate.,"Gustatory hyperhidrosis is facial sweating usually associated with the eating of hot spicy food or even smelling this food. Current options of treatment include oral anticholinergic drugs, the topical application of anticholinergics or aluminum chloride, and the injection of botulinum toxin. Thirteen patients have been treated to date with 1.5% or 2% topical glycopyrrolate. All patients had gustatory hyperhidrosis, which interfered with their social activities, after transthroacic endoscopic sympathectomy, and which was associated with compensatory focal hyperhidrosis. After applying topical glycopyrrolate, the subjective effect was excellent (no sweating after eating hot spicy food) in 10 patients (77%), and fair (clearly reduced sweating) in 3 patients (23%). All had reported incidents of being very embarrassed whilst eating hot spicy foods. Adverse effects included a mildly dry mouth and a sore throat in 2 patients (2% glycopyrrolate), a light headache in 1 patient (1.5% glycopyrrolate). The topical application of a glycopyrrolate pad appeared to be safe, efficacious, well tolerated, and a convenient method of treatment for moderate to severe symptoms of gustatory hyperhidrosis in post transthoracic endoscopic sympathectomy or sympathicotomy patients, with few side effects.","[{'text': 'gustatory hyperhidrosis', 'type': 'Disease', 'start': 26, 'end': 49, 'mesh': 'D013547'}, {'text': 'glycopyrrolate', 'type': 'Chemical', 'start': 63, 'end': 77, 'mesh': 'D006024'}, {'text': 'Gustatory hyperhidrosis', 'type': 'Disease', 'start': 79, 'end': 102, 'mesh': 'D013547'}, {'text': 'sweating', 'type': 'Disease', 'start': 113, 'end': 121, 'mesh': 'D013547'}, {'text': 'aluminum chloride', 'type': 'Chemical', 'start': 315, 'end': 332, 'mesh': 'C010845'}, {'text': 'glycopyrrolate', 'type': 'Chemical', 'start': 440, 'end': 454, 'mesh': 'D006024'}, {'text': 'gustatory hyperhidrosis', 'type': 'Disease', 'start': 473, 'end': 496, 'mesh': 'D013547'}, {'text': 'hyperhidrosis', 'type': 'Disease', 'start': 640, 'end': 653, 'mesh': 'D006945'}, {'text': 'glycopyrrolate', 'type': 'Chemical', 'start': 678, 'end': 692, 'mesh': 'D006024'}, {'text': 'sweating', 'type': 'Disease', 'start': 734, 'end': 742, 'mesh': 'D013547'}, {'text': 'sweating', 'type': 'Disease', 'start': 820, 'end': 828, 'mesh': 'D013547'}, {'text': 'dry mouth', 'type': 'Disease', 'start': 969, 'end': 978, 'mesh': 'D014987'}, {'text': 'sore throat', 'type': 'Disease', 'start': 985, 'end': 996, 'mesh': 'D010612'}, {'text': 'glycopyrrolate', 'type': 'Chemical', 'start': 1015, 'end': 1029, 'mesh': 'D006024'}, {'text': 'headache', 'type': 'Disease', 'start': 1040, 'end': 1048, 'mesh': 'D006261'}, {'text': 'glycopyrrolate', 'type': 'Chemical', 'start': 1068, 'end': 1082, 'mesh': 'D006024'}, {'text': 'glycopyrrolate', 'type': 'Chemical', 'start': 1114, 'end': 1128, 'mesh': 'D006024'}, {'text': 'gustatory hyperhidrosis', 'type': 'Disease', 'start': 1255, 'end': 1278, 'mesh': 'D013547'}]"
+1381,14616590,Pharmacological characteristics and side effects of a new galenic formulation of propofol without soyabean oil.,"We compared the pharmacokinetics, pharmacodynamics and safety profile of a new galenic formulation of propofol (AM149 1%), which does not contain soyabean oil, with a standard formulation of propofol (Disoprivan 1%). In a randomised, double-blind, cross-over study, 30 healthy volunteers received a single intravenous bolus injection of 2.5 mg.kg-1 propofol. Plasma propofol levels were measured for 48 h following drug administration and evaluated according to a three-compartment model. The pharmacodynamic parameters assessed included induction and emergence times, respiratory and cardiovascular effects, and pain on injection. Patients were monitored for side effects over 48 h. Owing to a high incidence of thrombophlebitis, the study was terminated prematurely and only the data of the two parallel treatment groups (15 patients in each group) were analysed. Plasma concentrations did not differ significantly between the two formulations. Anaesthesia induction and emergence times, respiratory and cardiovascular variables showed no significant differences between the two treatment groups. Pain on injection (80 vs. 20%, p < 0.01) and thrombophlebitis (93.3 vs. 6.6%, p < 0.001) occurred more frequently with AM149 than with Disoprivan. Although both formulations had similar pharmacokinetic and pharmacodynamic profiles the new formulation is not suitable for clinical use due to the high incidence of thrombophlebitis produced.","[{'text': 'propofol', 'type': 'Chemical', 'start': 81, 'end': 89, 'mesh': 'D015742'}, {'text': 'propofol', 'type': 'Chemical', 'start': 214, 'end': 222, 'mesh': 'D015742'}, {'text': 'propofol', 'type': 'Chemical', 'start': 303, 'end': 311, 'mesh': 'D015742'}, {'text': 'Disoprivan', 'type': 'Chemical', 'start': 313, 'end': 323, 'mesh': 'D015742'}, {'text': 'propofol', 'type': 'Chemical', 'start': 461, 'end': 469, 'mesh': 'D015742'}, {'text': 'propofol', 'type': 'Chemical', 'start': 478, 'end': 486, 'mesh': 'D015742'}, {'text': 'pain', 'type': 'Disease', 'start': 725, 'end': 729, 'mesh': 'D010146'}, {'text': 'thrombophlebitis', 'type': 'Disease', 'start': 825, 'end': 841, 'mesh': 'D013924'}, {'text': 'Pain', 'type': 'Disease', 'start': 1211, 'end': 1215, 'mesh': 'D010146'}, {'text': 'thrombophlebitis', 'type': 'Disease', 'start': 1256, 'end': 1272, 'mesh': 'D013924'}, {'text': 'Disoprivan', 'type': 'Chemical', 'start': 1346, 'end': 1356, 'mesh': 'D015742'}, {'text': 'thrombophlebitis', 'type': 'Disease', 'start': 1524, 'end': 1540, 'mesh': 'D013924'}]"
+1382,14748761,Vinorelbine-related cardiac events: a meta-analysis of randomized clinical trials.,"Several cases of cardiac adverse reactions related to vinorelbine (VNR) have been reported in the literature. In order to quantify the incidence of these cardiac events, we performed a meta-analysis of clinical trials comparing VNR with other chemotherapeutic agents in the treatment of various malignancies. Randomized clinical trials comparing VNR with other drugs in the treatment of cancer were searched in Medline, Embase, Evidence-based Medicine Reviews databases and the Cochrane library from 1987 to 2002. Outcomes of interest were severe cardiac events, toxic deaths and cardiac event-related deaths reported in each publication. We found 19 trials, involving 2441 patients treated by VNR and 2050 control patients. The incidence of cardiac events with VNR was 1.19% [95% confidence interval (CI) (0.75; 1.67)]. There was no difference in the risk of cardiac events between VNR and other drugs [odds ratio: 0.92, 95% CI (0.54; 1.55)]. The risk of VNR cardiac events was similar to vindesine (VDS) and other cardiotoxic drugs [fluorouracil, anthracyclines, gemcitabine (GEM) em leader ]. Even if it did not reach statistical significance because of a few number of cases, the risk was lower in trials excluding patients with cardiac history, and seemed to be higher in trials including patients with pre-existing cardiac diseases. Vinorelbine-related cardiac events concern about 1% of treated patients in clinical trials. However, the risk associated with VNR seems to be similar to that of other chemotherapeutic agents in the same indications.","[{'text': 'Vinorelbine', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'C030852'}, {'text': 'vinorelbine', 'type': 'Chemical', 'start': 137, 'end': 148, 'mesh': 'C030852'}, {'text': 'VNR', 'type': 'Chemical', 'start': 150, 'end': 153, 'mesh': 'C030852'}, {'text': 'VNR', 'type': 'Chemical', 'start': 311, 'end': 314, 'mesh': 'C030852'}, {'text': 'malignancies', 'type': 'Disease', 'start': 378, 'end': 390, 'mesh': 'D009369'}, {'text': 'VNR', 'type': 'Chemical', 'start': 429, 'end': 432, 'mesh': 'C030852'}, {'text': 'cancer', 'type': 'Disease', 'start': 470, 'end': 476, 'mesh': 'D009369'}, {'text': 'VNR', 'type': 'Chemical', 'start': 777, 'end': 780, 'mesh': 'C030852'}, {'text': 'VNR', 'type': 'Chemical', 'start': 845, 'end': 848, 'mesh': 'C030852'}, {'text': 'VNR', 'type': 'Chemical', 'start': 966, 'end': 969, 'mesh': 'C030852'}, {'text': 'VNR', 'type': 'Chemical', 'start': 1039, 'end': 1042, 'mesh': 'C030852'}, {'text': 'vindesine', 'type': 'Chemical', 'start': 1073, 'end': 1082, 'mesh': 'D014751'}, {'text': 'VDS', 'type': 'Chemical', 'start': 1084, 'end': 1087, 'mesh': 'D014751'}, {'text': 'cardiotoxic', 'type': 'Disease', 'start': 1099, 'end': 1110, 'mesh': 'D066126'}, {'text': 'fluorouracil', 'type': 'Chemical', 'start': 1118, 'end': 1130, 'mesh': 'D005472'}, {'text': 'anthracyclines', 'type': 'Chemical', 'start': 1132, 'end': 1146, 'mesh': 'D018943'}, {'text': 'gemcitabine', 'type': 'Chemical', 'start': 1148, 'end': 1159, 'mesh': 'C056507'}, {'text': 'GEM', 'type': 'Chemical', 'start': 1161, 'end': 1164, 'mesh': 'C056507'}, {'text': 'cardiac diseases', 'type': 'Disease', 'start': 1404, 'end': 1420, 'mesh': 'D006331'}, {'text': 'Vinorelbine', 'type': 'Chemical', 'start': 1422, 'end': 1433, 'mesh': 'C030852'}, {'text': 'VNR', 'type': 'Chemical', 'start': 1548, 'end': 1551, 'mesh': 'C030852'}]"
+1383,15018178,MRI findings of hypoxic cortical laminar necrosis in a child with hemolytic anemia crisis.,"We present magnetic resonance imaging findings of a 5-year-old girl who had a rapidly installing hemolytic anemia crisis induced by trimethoprim-sulfomethoxazole, resulting in cerebral anoxia leading to permanent damage. Magnetic Resonance imaging revealed cortical laminar necrosis in arterial border zones in both cerebral hemispheres, ischemic changes in subcortical white matter of left cerebral hemisphere, and in the left putamen. Although cortical laminar necrosis is a classic entity in adulthood related to conditions of energy depletions, there are few reports available in children. A wide review of the literature is also presented.","[{'text': 'necrosis', 'type': 'Disease', 'start': 41, 'end': 49, 'mesh': 'D009336'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 66, 'end': 82, 'mesh': 'D000743'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 188, 'end': 204, 'mesh': 'D000743'}, {'text': 'trimethoprim-sulfomethoxazole', 'type': 'Chemical', 'start': 223, 'end': 252, 'mesh': 'D015662'}, {'text': 'cerebral anoxia', 'type': 'Disease', 'start': 267, 'end': 282, 'mesh': 'D002534'}, {'text': 'necrosis', 'type': 'Disease', 'start': 365, 'end': 373, 'mesh': 'D009336'}, {'text': 'necrosis', 'type': 'Disease', 'start': 554, 'end': 562, 'mesh': 'D009336'}]"
+1384,15094729,The natural history of Vigabatrin associated visual field defects in patients electing to continue their medication.,"PURPOSE: To determine the natural history of visual field defects in a group of patients known to have Vigabatrin-associated changes who elected to continue the medication because of good seizure control. METHODS: All patients taking Vigabatrin alone or in combination with other antiepileptic drugs for at least 5 years (range 5-12 years) were entered into a visual surveillance programme. Patients were followed up at 6-monthly intervals for not less than 18 months (range 18-43 months). In all, 16 patients with unequivocal defects continued the medication. Following already published methodology (Eye 2002; 16;567-571) monocular mean radial degrees (MRDs) to the I/4e isopter on Goldmann perimetry was calculated for the right eye at the time of discovery of a visual field defect and again after not less than 18 months follow-up. RESULTS: Mean right eye MRD at presentation was 36.98 degrees (range 22.25-51.0), compared to 38.40 degrees (range 22.5-49.75) after follow-up; P=0.338 unpaired t-test. Only one patient demonstrated a deterioration in visual field during the study period and discontinued treatment. CONCLUSION: Established visual field defects presumed to be due to Vigabatrin therapy did not usually progress in spite of continuing use of the medication. These data give support to the hypothesis that the pathogenesis of Vigabatrin-associated visual field defects may be an idiosyncratic adverse drug reaction rather than dose-dependent toxicity.","[{'text': 'Vigabatrin', 'type': 'Chemical', 'start': 23, 'end': 33, 'mesh': 'D020888'}, {'text': 'visual field defects', 'type': 'Disease', 'start': 45, 'end': 65, 'mesh': 'D014786'}, {'text': 'visual field defects', 'type': 'Disease', 'start': 162, 'end': 182, 'mesh': 'D014786'}, {'text': 'Vigabatrin', 'type': 'Chemical', 'start': 220, 'end': 230, 'mesh': 'D020888'}, {'text': 'seizure', 'type': 'Disease', 'start': 305, 'end': 312, 'mesh': 'D012640'}, {'text': 'Vigabatrin', 'type': 'Chemical', 'start': 351, 'end': 361, 'mesh': 'D020888'}, {'text': 'visual field defect', 'type': 'Disease', 'start': 883, 'end': 902, 'mesh': 'D014786'}, {'text': 'deterioration in visual field', 'type': 'Disease', 'start': 1155, 'end': 1184, 'mesh': 'D014786'}, {'text': 'visual field defects', 'type': 'Disease', 'start': 1261, 'end': 1281, 'mesh': 'D014786'}, {'text': 'Vigabatrin', 'type': 'Chemical', 'start': 1304, 'end': 1314, 'mesh': 'D020888'}, {'text': 'Vigabatrin', 'type': 'Chemical', 'start': 1461, 'end': 1471, 'mesh': 'D020888'}, {'text': 'visual field defects', 'type': 'Disease', 'start': 1483, 'end': 1503, 'mesh': 'D014786'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1577, 'end': 1585, 'mesh': 'D064420'}]"
+1385,15096374,Induction of rosaceiform dermatitis during treatment of facial inflammatory dermatoses with tacrolimus ointment.,"BACKGROUND: Tacrolimus ointment is increasingly used for anti-inflammatory treatment of sensitive areas such as the face, and recent observations indicate that the treatment is effective in steroid-aggravated rosacea and perioral dermatitis. We report on rosaceiform dermatitis as a complication of treatment with tacrolimus ointment. OBSERVATIONS: Six adult patients with inflammatory facial dermatoses were treated with tacrolimus ointment because of the ineffectiveness of standard treatments. Within 2 to 3 weeks of initially effective and well-tolerated treatment, 3 patients with a history of rosacea and 1 with a history of acne experienced sudden worsening with pustular rosaceiform lesions. Biopsy revealed an abundance of Demodex mites in 2 of these patients. In 1 patient with eyelid eczema, rosaceiform periocular dermatitis gradually appeared after 3 weeks of treatment. In 1 patient with atopic dermatitis, telangiectatic and papular rosacea insidiously appeared after 5 months of treatment. CONCLUSIONS: Our observations suggest that the spectrum of rosaceiform dermatitis as a complication of treatment with tacrolimus ointment is heterogeneous. A variety of factors, such as vasoactive properties of tacrolimus, proliferation of Demodex due to local immunosuppression, and the occlusive properties of the ointment, may be involved in the observed phenomena. Future studies are needed to identify individual risk factors.","[{'text': 'dermatitis', 'type': 'Disease', 'start': 25, 'end': 35, 'mesh': 'D003872'}, {'text': 'facial inflammatory dermatoses', 'type': 'Disease', 'start': 56, 'end': 86, 'mesh': 'D005148'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 92, 'end': 102, 'mesh': 'D016559'}, {'text': 'Tacrolimus', 'type': 'Chemical', 'start': 125, 'end': 135, 'mesh': 'D016559'}, {'text': 'steroid', 'type': 'Chemical', 'start': 303, 'end': 310, 'mesh': 'D013256'}, {'text': 'rosacea', 'type': 'Disease', 'start': 322, 'end': 329, 'mesh': 'D012393'}, {'text': 'perioral dermatitis', 'type': 'Disease', 'start': 334, 'end': 353, 'mesh': 'D019557'}, {'text': 'dermatitis', 'type': 'Disease', 'start': 380, 'end': 390, 'mesh': 'D003872'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 427, 'end': 437, 'mesh': 'D016559'}, {'text': 'inflammatory facial dermatoses', 'type': 'Disease', 'start': 486, 'end': 516, 'mesh': 'D005148'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 535, 'end': 545, 'mesh': 'D016559'}, {'text': 'rosacea', 'type': 'Disease', 'start': 712, 'end': 719, 'mesh': 'D012393'}, {'text': 'acne', 'type': 'Disease', 'start': 744, 'end': 748, 'mesh': 'D000152'}, {'text': 'eczema', 'type': 'Disease', 'start': 908, 'end': 914, 'mesh': 'D004485'}, {'text': 'periocular dermatitis', 'type': 'Disease', 'start': 928, 'end': 949, 'mesh': 'D019557'}, {'text': 'atopic dermatitis', 'type': 'Disease', 'start': 1015, 'end': 1032, 'mesh': 'D003876'}, {'text': 'papular rosacea', 'type': 'Disease', 'start': 1053, 'end': 1068, 'mesh': 'D012393'}, {'text': 'dermatitis', 'type': 'Disease', 'start': 1190, 'end': 1200, 'mesh': 'D003872'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 1237, 'end': 1247, 'mesh': 'D016559'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 1330, 'end': 1340, 'mesh': 'D016559'}]"
+1386,15229250,Structural abnormalities in the brains of human subjects who use methamphetamine.,"We visualize, for the first time, the profile of structural deficits in the human brain associated with chronic methamphetamine (MA) abuse. Studies of human subjects who have used MA chronically have revealed deficits in dopaminergic and serotonergic systems and cerebral metabolic abnormalities. Using magnetic resonance imaging (MRI) and new computational brain-mapping techniques, we determined the pattern of structural brain alterations associated with chronic MA abuse in human subjects and related these deficits to cognitive impairment. We used high-resolution MRI and surface-based computational image analyses to map regional abnormalities in the cortex, hippocampus, white matter, and ventricles in 22 human subjects who used MA and 21 age-matched, healthy controls. Cortical maps revealed severe gray-matter deficits in the cingulate, limbic, and paralimbic cortices of MA abusers (averaging 11.3% below control; p < 0.05). On average, MA abusers had 7.8% smaller hippocampal volumes than control subjects (p < 0.01; left, p = 0.01; right, p < 0.05) and significant white-matter hypertrophy (7.0%; p < 0.01). Hippocampal deficits were mapped and correlated with memory performance on a word-recall test (p < 0.05). MRI-based maps suggest that chronic methamphetamine abuse causes a selective pattern of cerebral deterioration that contributes to impaired memory performance. MA may selectively damage the medial temporal lobe and, consistent with metabolic studies, the cingulate-limbic cortex, inducing neuroadaptation, neuropil reduction, or cell death. Prominent white-matter hypertrophy may result from altered myelination and adaptive glial changes, including gliosis secondary to neuronal damage. These brain substrates may help account for the symptoms of MA abuse, providing therapeutic targets for drug-induced brain injury.","[{'text': 'methamphetamine', 'type': 'Chemical', 'start': 65, 'end': 80, 'mesh': 'D008694'}, {'text': 'structural deficits in the human brain', 'type': 'Disease', 'start': 131, 'end': 169, 'mesh': 'D001930'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 194, 'end': 209, 'mesh': 'D008694'}, {'text': 'MA', 'type': 'Chemical', 'start': 211, 'end': 213, 'mesh': 'D008694'}, {'text': 'MA', 'type': 'Chemical', 'start': 262, 'end': 264, 'mesh': 'D008694'}, {'text': 'metabolic abnormalities', 'type': 'Disease', 'start': 354, 'end': 377, 'mesh': 'D008659'}, {'text': 'MA', 'type': 'Chemical', 'start': 548, 'end': 550, 'mesh': 'D008694'}, {'text': 'cognitive impairment', 'type': 'Disease', 'start': 605, 'end': 625, 'mesh': 'D003072'}, {'text': 'abnormalities in the cortex, hippocampus, white matter, and ventricles', 'type': 'Disease', 'start': 718, 'end': 788, 'mesh': 'D001930'}, {'text': 'MA', 'type': 'Chemical', 'start': 819, 'end': 821, 'mesh': 'D008694'}, {'text': 'MA', 'type': 'Chemical', 'start': 964, 'end': 966, 'mesh': 'D008694'}, {'text': 'MA', 'type': 'Chemical', 'start': 1030, 'end': 1032, 'mesh': 'D008694'}, {'text': 'hypertrophy', 'type': 'Disease', 'start': 1173, 'end': 1184, 'mesh': 'D006984'}, {'text': 'methamphetamine', 'type': 'Chemical', 'start': 1345, 'end': 1360, 'mesh': 'D008694'}, {'text': 'impaired memory performance', 'type': 'Disease', 'start': 1440, 'end': 1467, 'mesh': 'D008569'}, {'text': 'MA', 'type': 'Chemical', 'start': 1469, 'end': 1471, 'mesh': 'D008694'}, {'text': 'hypertrophy', 'type': 'Disease', 'start': 1673, 'end': 1684, 'mesh': 'D006984'}, {'text': 'gliosis', 'type': 'Disease', 'start': 1759, 'end': 1766, 'mesh': 'D005911'}, {'text': 'neuronal damage', 'type': 'Disease', 'start': 1780, 'end': 1795, 'mesh': 'D009422'}, {'text': 'MA', 'type': 'Chemical', 'start': 1857, 'end': 1859, 'mesh': 'D008694'}, {'text': 'brain injury', 'type': 'Disease', 'start': 1914, 'end': 1926, 'mesh': 'D001930'}]"
+1387,15265979,Disruption of hepatic lipid homeostasis in mice after amiodarone treatment is associated with peroxisome proliferator-activated receptor-alpha target gene activation.,"Amiodarone, an efficacious and widely used antiarrhythmic agent, has been reported to cause hepatotoxicity in some patients. To gain insight into the mechanism of this unwanted effect, mice were administered various doses of amiodarone and examined for changes in hepatic histology and gene regulation. Amiodarone induced hepatomegaly, hepatocyte microvesicular lipid accumulation, and a significant decrease in serum triglycerides and glucose. Northern blot analysis of hepatic RNA revealed a dose-dependent increase in the expression of a number of genes critical for fatty acid oxidation, lipoprotein assembly, and lipid transport. Many of these genes are regulated by the peroxisome proliferator-activated receptor-alpha (PPARalpha), a ligand-activated nuclear hormone receptor transcription factor. The absence of induction of these genes as well as hepatomegaly in PPARalpha knockout [PPARalpha-/-] mice indicated that the effects of amiodarone were dependent upon the presence of a functional PPARalpha gene. Compared to wild-type mice, treatment of PPARalpha-/- mice with amiodarone resulted in an increased rate and extent of total body weight loss. The inability of amiodarone to directly activate either human or mouse PPARalpha transiently expressed in human HepG2 hepatoma cells indicates that the effects of amiodarone on the function of this receptor were indirect. Based upon these results, we conclude that amiodarone disrupts hepatic lipid homeostasis and that the increased expression of PPARalpha target genes is secondary to this toxic effect. These results provide important new mechanistic information regarding the hepatotoxic effects of amiodarone and indicate that PPARalpha protects against amiodarone-induced hepatotoxicity.","[{'text': 'amiodarone', 'type': 'Chemical', 'start': 54, 'end': 64, 'mesh': 'D000638'}, {'text': 'Amiodarone', 'type': 'Chemical', 'start': 167, 'end': 177, 'mesh': 'D000638'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 259, 'end': 273, 'mesh': 'D056486'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 392, 'end': 402, 'mesh': 'D000638'}, {'text': 'Amiodarone', 'type': 'Chemical', 'start': 470, 'end': 480, 'mesh': 'D000638'}, {'text': 'hepatomegaly', 'type': 'Disease', 'start': 489, 'end': 501, 'mesh': 'D006529'}, {'text': 'triglycerides', 'type': 'Chemical', 'start': 585, 'end': 598, 'mesh': 'D014280'}, {'text': 'glucose', 'type': 'Chemical', 'start': 603, 'end': 610, 'mesh': 'D005947'}, {'text': 'fatty acid', 'type': 'Chemical', 'start': 737, 'end': 747, 'mesh': 'D005227'}, {'text': 'hepatomegaly', 'type': 'Disease', 'start': 1022, 'end': 1034, 'mesh': 'D006529'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 1107, 'end': 1117, 'mesh': 'D000638'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 1247, 'end': 1257, 'mesh': 'D000638'}, {'text': 'weight loss', 'type': 'Disease', 'start': 1313, 'end': 1324, 'mesh': 'D015431'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 1343, 'end': 1353, 'mesh': 'D000638'}, {'text': 'hepatoma', 'type': 'Disease', 'start': 1444, 'end': 1452, 'mesh': 'D006528'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 1489, 'end': 1499, 'mesh': 'D000638'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 1591, 'end': 1601, 'mesh': 'D000638'}, {'text': 'hepatotoxic', 'type': 'Disease', 'start': 1806, 'end': 1817, 'mesh': 'D056486'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 1829, 'end': 1839, 'mesh': 'D000638'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 1885, 'end': 1895, 'mesh': 'D000638'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 1904, 'end': 1918, 'mesh': 'D056486'}]"
+1388,15276093,Safety and compliance with once-daily niacin extended-release/lovastatin as initial therapy in the Impact of Medical Subspecialty on Patient Compliance to Treatment (IMPACT) study.,"Niacin extended-release/lovastatin is a new combination product approved for treatment of primary hypercholesterolemia and mixed dyslipidemia. This open-labeled, multicenter study evaluated the safety of bedtime niacin extended-release/lovastatin when dosed as initial therapy and patient compliance to treatment in various clinical practice settings. A total of 4,499 patients with dyslipidemia requiring drug intervention was enrolled at 1,081 sites. Patients were treated with 1 tablet (500 mg of niacin extended-release/20 mg of lovastatin) once nightly for 4 weeks and then 2 tablets for 8 weeks. Patients also received dietary counseling, educational materials, and reminders to call a toll-free number that provided further education about dyslipidemia and niacin extended-release/lovastatin. Primary end points were study compliance, increases in liver transaminases to >3 times the upper limit of normal, and clinical myopathy. Final study status was available for 4,217 patients (94%). Compliance to niacin extended-release/lovastatin was 77%, with 3,245 patients completing the study. Patients in the southeast and those enrolled by endocrinologists had the lowest compliance and highest adverse event rates. Flushing was the most common adverse event, reported by 18% of patients and leading to discontinuation by 6%. Incidence of increased aspartate aminotransferase and/or alanine aminotransferase >3 times the upper limit of normal was <0.3%. An increase of creatine phosphokinase to >5 times the upper limit of normal occurred in 0.24% of patients, and no cases of drug-induced myopathy were observed. Niacin extended-release/lovastatin 1,000/40 mg, dosed as initial therapy, was associated with good compliance and safety and had very low incidences of increased liver and muscle enzymes.","[{'text': 'niacin extended-release/lovastatin', 'type': 'Chemical', 'start': 38, 'end': 72, 'mesh': 'C451780'}, {'text': 'Niacin extended-release/lovastatin', 'type': 'Chemical', 'start': 181, 'end': 215, 'mesh': 'C451780'}, {'text': 'hypercholesterolemia', 'type': 'Disease', 'start': 279, 'end': 299, 'mesh': 'D006937'}, {'text': 'dyslipidemia', 'type': 'Disease', 'start': 310, 'end': 322, 'mesh': 'D050171'}, {'text': 'niacin extended-release/lovastatin', 'type': 'Chemical', 'start': 393, 'end': 427, 'mesh': 'C451780'}, {'text': 'dyslipidemia', 'type': 'Disease', 'start': 564, 'end': 576, 'mesh': 'D050171'}, {'text': 'niacin', 'type': 'Chemical', 'start': 681, 'end': 687, 'mesh': 'D009525'}, {'text': 'lovastatin', 'type': 'Chemical', 'start': 714, 'end': 724, 'mesh': 'D008148'}, {'text': 'dyslipidemia', 'type': 'Disease', 'start': 928, 'end': 940, 'mesh': 'D050171'}, {'text': 'niacin extended-release/lovastatin', 'type': 'Chemical', 'start': 945, 'end': 979, 'mesh': 'C451780'}, {'text': 'myopathy', 'type': 'Disease', 'start': 1108, 'end': 1116, 'mesh': 'D009135'}, {'text': 'niacin extended-release/lovastatin', 'type': 'Chemical', 'start': 1191, 'end': 1225, 'mesh': 'C451780'}, {'text': 'Flushing', 'type': 'Disease', 'start': 1401, 'end': 1409, 'mesh': 'D005483'}, {'text': 'aspartate', 'type': 'Chemical', 'start': 1534, 'end': 1543, 'mesh': 'D001224'}, {'text': 'alanine', 'type': 'Chemical', 'start': 1568, 'end': 1575, 'mesh': 'D000409'}, {'text': 'creatine', 'type': 'Chemical', 'start': 1654, 'end': 1662, 'mesh': 'D003401'}, {'text': 'myopathy', 'type': 'Disease', 'start': 1775, 'end': 1783, 'mesh': 'D009135'}, {'text': 'Niacin extended-release/lovastatin', 'type': 'Chemical', 'start': 1799, 'end': 1833, 'mesh': 'C451780'}]"
+1389,15282950,Protective effect of Terminalia chebula against experimental myocardial injury induced by isoproterenol.,"Cardioprotective effect of ethanolic extract of Terminalia chebula fruits (500 mg/kg body wt) was examined in isoproterenol (200 mg/kg body wt) induced myocardial damage in rats. In isoproterenol administered rats, the level of lipid peroxides increased significantly in the serum and heart. A significant decrease was observed in the activity of the myocardial marker enzymes with a concomitant increase in their activity in serum. Histopathological examination was carried out to confirm the myocardial necrosis. T. chebula extract pretreatment was found to ameliorate the effect of isoproterenol on lipid peroxide formation and retained the activities of the diagnostic marker enzymes.","[{'text': 'Terminalia chebula', 'type': 'Chemical', 'start': 21, 'end': 39, 'mesh': 'D010936'}, {'text': 'myocardial injury', 'type': 'Disease', 'start': 61, 'end': 78, 'mesh': 'D009202'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 90, 'end': 103, 'mesh': 'D007545'}, {'text': 'ethanolic extract of Terminalia chebula fruits', 'type': 'Chemical', 'start': 132, 'end': 178, 'mesh': 'D010936'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 215, 'end': 228, 'mesh': 'D007545'}, {'text': 'myocardial damage', 'type': 'Disease', 'start': 257, 'end': 274, 'mesh': 'D009202'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 287, 'end': 300, 'mesh': 'D007545'}, {'text': 'peroxides', 'type': 'Chemical', 'start': 339, 'end': 348, 'mesh': 'D010545'}, {'text': 'necrosis', 'type': 'Disease', 'start': 610, 'end': 618, 'mesh': 'D009336'}, {'text': 'T. chebula extract', 'type': 'Chemical', 'start': 620, 'end': 638, 'mesh': 'D010936'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 690, 'end': 703, 'mesh': 'D007545'}, {'text': 'peroxide', 'type': 'Chemical', 'start': 713, 'end': 721, 'mesh': 'D010545'}]"
+1390,15321332,A case of postoperative anxiety due to low dose droperidol used with patient-controlled analgesia.,"A multiparous woman in good psychological health underwent urgent caesarean section in labour. Postoperatively, she was given a patient-controlled analgesia device delivering boluses of diamorphine 0.5 mg and droperidol 0.025 mg. Whilst using the device she gradually became anxious, the feeling worsening after each bolus. The diagnosis of droperidol-induced psychological disturbance was not made straight away although on subsequent close questioning the patient gave a very clear history. After she had received a total of only 0.9 mg droperidol, a syringe containing diamorphine only was substituted and her unease resolved completely. We feel that, although the dramatic extrapyramidal side effects of dopaminergic antiemetics are well known, more subtle manifestations may easily be overlooked.","[{'text': 'anxiety', 'type': 'Disease', 'start': 24, 'end': 31, 'mesh': 'D001008'}, {'text': 'droperidol', 'type': 'Chemical', 'start': 48, 'end': 58, 'mesh': 'D004329'}, {'text': 'diamorphine', 'type': 'Chemical', 'start': 285, 'end': 296, 'mesh': 'D003932'}, {'text': 'droperidol', 'type': 'Chemical', 'start': 308, 'end': 318, 'mesh': 'D004329'}, {'text': 'droperidol', 'type': 'Chemical', 'start': 440, 'end': 450, 'mesh': 'D004329'}, {'text': 'psychological disturbance', 'type': 'Disease', 'start': 459, 'end': 484, 'mesh': 'D001008'}, {'text': 'droperidol', 'type': 'Chemical', 'start': 638, 'end': 648, 'mesh': 'D004329'}, {'text': 'diamorphine', 'type': 'Chemical', 'start': 671, 'end': 682, 'mesh': 'D003932'}]"
+1391,15366550,Accurate patient history contributes to differentiating diabetes insipidus: a case study.,"This case study highlights the important contribution of nursing in obtaining an accurate health history. The case discussed herein initially appeared to be neurogenic diabetes insipidus (DI) secondary to a traumatic brain injury. The nursing staff, by reviewing the patient's health history with his family, discovered a history of polydipsia and long-standing lithium use. Lithium is implicated in drug-induced nephrogenic DI, and because the patient had not received lithium since being admitted to the hospital, his treatment changed to focus on nephrogenic DI. By combining information from the patient history, the physical examination, and radiologic and laboratory studies, the critical care team demonstrated that the patient had been self-treating his lithium-induced nephrogenic DI and developed neurogenic DI secondary to brain trauma. Thus successful treatment required that nephrogenic and neurogenic DI be treated concomitantly.","[{'text': 'diabetes insipidus', 'type': 'Disease', 'start': 56, 'end': 74, 'mesh': 'D003919'}, {'text': 'neurogenic diabetes insipidus', 'type': 'Disease', 'start': 247, 'end': 276, 'mesh': 'D018500'}, {'text': 'DI', 'type': 'Disease', 'start': 278, 'end': 280, 'mesh': 'D003919'}, {'text': 'traumatic brain injury', 'type': 'Disease', 'start': 297, 'end': 319, 'mesh': 'D001930'}, {'text': 'polydipsia', 'type': 'Disease', 'start': 423, 'end': 433, 'mesh': 'D059606'}, {'text': 'lithium', 'type': 'Chemical', 'start': 452, 'end': 459, 'mesh': 'D008094'}, {'text': 'Lithium', 'type': 'Chemical', 'start': 465, 'end': 472, 'mesh': 'D008094'}, {'text': 'nephrogenic DI', 'type': 'Disease', 'start': 503, 'end': 517, 'mesh': 'D018500'}, {'text': 'lithium', 'type': 'Chemical', 'start': 560, 'end': 567, 'mesh': 'D008094'}, {'text': 'nephrogenic DI', 'type': 'Disease', 'start': 640, 'end': 654, 'mesh': 'D018500'}, {'text': 'lithium', 'type': 'Chemical', 'start': 852, 'end': 859, 'mesh': 'D008094'}, {'text': 'nephrogenic DI', 'type': 'Disease', 'start': 868, 'end': 882, 'mesh': 'D018500'}, {'text': 'neurogenic DI', 'type': 'Disease', 'start': 897, 'end': 910, 'mesh': 'D018500'}, {'text': 'brain trauma', 'type': 'Disease', 'start': 924, 'end': 936, 'mesh': 'D001930'}, {'text': 'neurogenic DI', 'type': 'Disease', 'start': 994, 'end': 1007, 'mesh': 'D018500'}]"
+1392,15482540,Factors contributing to ribavirin-induced anemia.,"BACKGROUND AND AIM: Interferon and ribavirin combination therapy for chronic hepatitis C produces hemolytic anemia. This study was conducted to identify the factors contributing to ribavirin-induced anemia. METHODS: Eighty-eight patients with chronic hepatitis C who received interferon-alpha-2b at a dose of 6 MU administered intramuscularly for 24 weeks in combination with ribavirin administered orally at a dose of 600 mg or 800 mg participated in the study. A hemoglobin concentration of <10 g/dL was defined as ribavirin-induced anemia. RESULTS: Ribavirin-induced anemia occurred in 18 (20.5%) patients during treatment. A 2 g/dL decrease in hemoglobin concentrations in patients with anemia was observed at week 2 after the start of treatment. The hemoglobin concentration in patients with > or =2 g/dL decrease at week 2 was observed to be significantly lower even after week 2 than in patients with <2 g/dL decrease (P < 0.01). A significant relationship was observed between the rate of reduction of hemoglobin concentrations at week 2 and the severity of anemia (P < 0.01). Such factors as sex (female), age (> or =60 years old), and the ribavirin dose by body weight (12 mg/kg or more) were significant by univariate analysis. CONCLUSIONS: Careful administration is necessary in patients > or =60 years old, in female patients, and in patients receiving a ribavirin dose of 12 mg/kg or more. Patients who experience a fall in hemoglobin concentrations of 2 g/dL or more at week 2 after the start of treatment should be monitored with particular care.","[{'text': 'ribavirin', 'type': 'Chemical', 'start': 24, 'end': 33, 'mesh': 'D012254'}, {'text': 'anemia', 'type': 'Disease', 'start': 42, 'end': 48, 'mesh': 'D000740'}, {'text': 'Interferon', 'type': 'Chemical', 'start': 70, 'end': 80, 'mesh': 'D016898'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 85, 'end': 94, 'mesh': 'D012254'}, {'text': 'chronic hepatitis C', 'type': 'Disease', 'start': 119, 'end': 138, 'mesh': 'D019698'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 148, 'end': 164, 'mesh': 'D000743'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 231, 'end': 240, 'mesh': 'D012254'}, {'text': 'anemia', 'type': 'Disease', 'start': 249, 'end': 255, 'mesh': 'D000740'}, {'text': 'chronic hepatitis C', 'type': 'Disease', 'start': 293, 'end': 312, 'mesh': 'D019698'}, {'text': 'interferon-alpha-2b', 'type': 'Chemical', 'start': 326, 'end': 345, 'mesh': 'D016898'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 426, 'end': 435, 'mesh': 'D012254'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 567, 'end': 576, 'mesh': 'D012254'}, {'text': 'anemia', 'type': 'Disease', 'start': 585, 'end': 591, 'mesh': 'D000740'}, {'text': 'Ribavirin', 'type': 'Chemical', 'start': 602, 'end': 611, 'mesh': 'D012254'}, {'text': 'anemia', 'type': 'Disease', 'start': 620, 'end': 626, 'mesh': 'D000740'}, {'text': 'anemia', 'type': 'Disease', 'start': 741, 'end': 747, 'mesh': 'D000740'}, {'text': 'anemia', 'type': 'Disease', 'start': 1116, 'end': 1122, 'mesh': 'D000740'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 1199, 'end': 1208, 'mesh': 'D012254'}, {'text': 'ribavirin', 'type': 'Chemical', 'start': 1418, 'end': 1427, 'mesh': 'D012254'}]"
+1393,15605432,Oxidative damage precedes nitrative damage in adriamycin-induced cardiac mitochondrial injury.,"The purpose of the present study was to determine if elevated reactive oxygen (ROS)/nitrogen species (RNS) reported to be present in adriamycin (ADR)-induced cardiotoxicity actually resulted in cardiomyocyte oxidative/nitrative damage, and to quantitatively determine the time course and subcellular localization of these postulated damage products using an in vivo approach. B6C3 mice were treated with a single dose of 20 mg/kg ADR. Ultrastructural damage and levels of 4-hydroxy-2-nonenal (4HNE)-protein adducts and 3-nitrotyrosine (3NT) were analyzed. Quantitative ultrastructural damage using computerized image techniques showed cardiomyocyte injury as early as 3 hours, with mitochondria being the most extensively and progressively injured subcellular organelle. Analysis of 4HNE protein adducts by immunogold electron microscopy showed appearance of 4HNE protein adducts in mitochondria as early as 3 hours, with a peak at 6 hours and subsequent decline at 24 hours. 3NT levels were significantly increased in all subcellular compartments at 6 hours and subsequently declined at 24 hours. Our data showed ADR induced 4HNE-protein adducts in mitochondria at the same time point as when mitochondrial injury initially appeared. These results document for the first time in vivo that mitochondrial oxidative damage precedes nitrative damage. The progressive nature of mitochondrial injury suggests that mitochondria, not other subcellular organelles, are the major site of intracellular injury.","[{'text': 'adriamycin', 'type': 'Chemical', 'start': 46, 'end': 56, 'mesh': 'D004317'}, {'text': 'mitochondrial injury', 'type': 'Disease', 'start': 73, 'end': 93, 'mesh': 'D028361'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 166, 'end': 172, 'mesh': 'D010100'}, {'text': 'nitrogen', 'type': 'Chemical', 'start': 179, 'end': 187, 'mesh': 'D009584'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 228, 'end': 238, 'mesh': 'D004317'}, {'text': 'ADR', 'type': 'Chemical', 'start': 240, 'end': 243, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 253, 'end': 267, 'mesh': 'D066126'}, {'text': 'ADR', 'type': 'Chemical', 'start': 525, 'end': 528, 'mesh': 'D004317'}, {'text': '4-hydroxy-2-nonenal', 'type': 'Chemical', 'start': 567, 'end': 586, 'mesh': 'C027576'}, {'text': '4HNE', 'type': 'Chemical', 'start': 588, 'end': 592, 'mesh': 'C027576'}, {'text': '3-nitrotyrosine', 'type': 'Chemical', 'start': 614, 'end': 629, 'mesh': 'C002744'}, {'text': '3NT', 'type': 'Chemical', 'start': 631, 'end': 634, 'mesh': 'C002744'}, {'text': '4HNE', 'type': 'Chemical', 'start': 878, 'end': 882, 'mesh': 'C027576'}, {'text': '4HNE', 'type': 'Chemical', 'start': 954, 'end': 958, 'mesh': 'C027576'}, {'text': '3NT', 'type': 'Chemical', 'start': 1071, 'end': 1074, 'mesh': 'C002744'}, {'text': 'ADR', 'type': 'Chemical', 'start': 1209, 'end': 1212, 'mesh': 'D004317'}, {'text': '4HNE', 'type': 'Chemical', 'start': 1221, 'end': 1225, 'mesh': 'C027576'}, {'text': 'mitochondrial injury', 'type': 'Disease', 'start': 1289, 'end': 1309, 'mesh': 'D028361'}, {'text': 'mitochondrial oxidative damage', 'type': 'Disease', 'start': 1385, 'end': 1415, 'mesh': 'D028361'}, {'text': 'mitochondrial injury', 'type': 'Disease', 'start': 1469, 'end': 1489, 'mesh': 'D028361'}]"
+1394,15609701,Sotalol-induced coronary spasm in a patient with dilated cardiomyopathy associated with sustained ventricular tachycardia.,"A 54-year-old man with severe left ventricular dysfunction due to dilated cardiomyopathy was referred to our hospital for symptomatic incessant sustained ventricular tachycardia (VT). After the administration of nifekalant hydrochloride, sustained VT was terminated. An alternate class III agent, sotalol, was also effective for the prevention of VT. However, one month after switching over nifekalant to sotalol, a short duration of ST elevation was documented in ECG monitoring at almost the same time for three consecutive days. ST elevation with chest discomfort disappeared since he began taking long-acting diltiazem. Coronary vasospasm may be induced by the non-selective beta-blocking properties of sotalol.","[{'text': 'Sotalol', 'type': 'Chemical', 'start': 0, 'end': 7, 'mesh': 'D013015'}, {'text': 'coronary spasm', 'type': 'Disease', 'start': 16, 'end': 30, 'mesh': 'D003329'}, {'text': 'dilated cardiomyopathy', 'type': 'Disease', 'start': 49, 'end': 71, 'mesh': 'D002311'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 98, 'end': 121, 'mesh': 'D017180'}, {'text': 'ventricular dysfunction', 'type': 'Disease', 'start': 158, 'end': 181, 'mesh': 'D018754'}, {'text': 'dilated cardiomyopathy', 'type': 'Disease', 'start': 189, 'end': 211, 'mesh': 'D002311'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 277, 'end': 300, 'mesh': 'D017180'}, {'text': 'VT', 'type': 'Disease', 'start': 302, 'end': 304, 'mesh': 'D017180'}, {'text': 'nifekalant hydrochloride', 'type': 'Chemical', 'start': 335, 'end': 359, 'mesh': 'C076259'}, {'text': 'VT', 'type': 'Disease', 'start': 371, 'end': 373, 'mesh': 'D017180'}, {'text': 'sotalol', 'type': 'Chemical', 'start': 420, 'end': 427, 'mesh': 'D013015'}, {'text': 'VT', 'type': 'Disease', 'start': 470, 'end': 472, 'mesh': 'D017180'}, {'text': 'nifekalant', 'type': 'Chemical', 'start': 514, 'end': 524, 'mesh': 'C076259'}, {'text': 'sotalol', 'type': 'Chemical', 'start': 528, 'end': 535, 'mesh': 'D013015'}, {'text': 'diltiazem', 'type': 'Chemical', 'start': 736, 'end': 745, 'mesh': 'D004110'}, {'text': 'Coronary vasospasm', 'type': 'Disease', 'start': 747, 'end': 765, 'mesh': 'D003329'}, {'text': 'sotalol', 'type': 'Chemical', 'start': 830, 'end': 837, 'mesh': 'D013015'}]"
+1395,15614572,"Effects of the antidepressant trazodone, a 5-HT 2A/2C receptor antagonist, on dopamine-dependent behaviors in rats.","RATIONALE: 5-Hydroxytryptamine, via stimulation of 5-HT 2C receptors, exerts a tonic inhibitory influence on dopaminergic neurotransmission, whereas activation of 5-HT 2A receptors enhances stimulated DAergic neurotransmission. The antidepressant trazodone is a 5-HT 2A/2C receptor antagonist. OBJECTIVES: To evaluate the effect of trazodone treatment on behaviors dependent on the functional status of the nigrostriatal DAergic system. METHODS: The effect of pretreatment with trazodone on dexamphetamine- and apomorphine-induced oral stereotypies, on catalepsy induced by haloperidol and apomorphine (0.05 mg/kg, i.p.), on ergometrine-induced wet dog shake (WDS) behavior and fluoxetine-induced penile erections was studied in rats. We also investigated whether trazodone induces catalepsy in rats. RESULTS: Trazodone at 2.5-20 mg/kg i.p. did not induce catalepsy, and did not antagonize apomorphine (1.5 and 3 mg/kg) stereotypy and apomorphine (0.05 mg/kg)-induced catalepsy. However, pretreatment with 5, 10 and 20 mg/kg i.p. trazodone enhanced dexamphetamine stereotypy, and antagonized haloperidol catalepsy, ergometrine-induced WDS behavior and fluoxetine-induced penile erections. Trazodone at 30, 40 and 50 mg/kg i.p. induced catalepsy and antagonized apomorphine and dexamphetamine stereotypies. CONCLUSIONS: Our results indicate that trazodone at 2.5-20 mg/kg does not block pre- and postsynaptic striatal D2 DA receptors, while at 30, 40 and 50 mg/kg it blocks postsynaptic striatal D2 DA receptors. Furthermore, at 5, 10 and 20 mg/kg, trazodone blocks 5-HT 2A and 5-HT 2C receptors. We suggest that trazodone (5, 10 and 20 mg/kg), by blocking the 5-HT 2C receptors, releases the nigrostriatal DAergic neurons from tonic inhibition caused by 5-HT, and thereby potentiates dexamphetamine stereotypy and antagonizes haloperidol catalepsy.","[{'text': 'trazodone', 'type': 'Chemical', 'start': 30, 'end': 39, 'mesh': 'D014196'}, {'text': '5-HT', 'type': 'Chemical', 'start': 43, 'end': 47, 'mesh': 'D012701'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 78, 'end': 86, 'mesh': 'D004298'}, {'text': '5-Hydroxytryptamine', 'type': 'Chemical', 'start': 127, 'end': 146, 'mesh': 'D012701'}, {'text': '5-HT', 'type': 'Chemical', 'start': 167, 'end': 171, 'mesh': 'D012701'}, {'text': '5-HT', 'type': 'Chemical', 'start': 279, 'end': 283, 'mesh': 'D012701'}, {'text': 'trazodone', 'type': 'Chemical', 'start': 363, 'end': 372, 'mesh': 'D014196'}, {'text': '5-HT', 'type': 'Chemical', 'start': 378, 'end': 382, 'mesh': 'D012701'}, {'text': 'trazodone', 'type': 'Chemical', 'start': 448, 'end': 457, 'mesh': 'D014196'}, {'text': 'trazodone', 'type': 'Chemical', 'start': 594, 'end': 603, 'mesh': 'D014196'}, {'text': 'dexamphetamine', 'type': 'Chemical', 'start': 607, 'end': 621, 'mesh': 'D003913'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 627, 'end': 638, 'mesh': 'D001058'}, {'text': 'oral stereotypies', 'type': 'Disease', 'start': 647, 'end': 664, 'mesh': 'D009062'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 669, 'end': 678, 'mesh': 'D002375'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 690, 'end': 701, 'mesh': 'D006220'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 706, 'end': 717, 'mesh': 'D001058'}, {'text': 'ergometrine', 'type': 'Chemical', 'start': 741, 'end': 752, 'mesh': 'D004874'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 794, 'end': 804, 'mesh': 'D005473'}, {'text': 'trazodone', 'type': 'Chemical', 'start': 880, 'end': 889, 'mesh': 'D014196'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 898, 'end': 907, 'mesh': 'D002375'}, {'text': 'Trazodone', 'type': 'Chemical', 'start': 926, 'end': 935, 'mesh': 'D014196'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 972, 'end': 981, 'mesh': 'D002375'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 1006, 'end': 1017, 'mesh': 'D001058'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 1051, 'end': 1062, 'mesh': 'D001058'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 1084, 'end': 1093, 'mesh': 'D002375'}, {'text': 'trazodone', 'type': 'Chemical', 'start': 1146, 'end': 1155, 'mesh': 'D014196'}, {'text': 'dexamphetamine', 'type': 'Chemical', 'start': 1165, 'end': 1179, 'mesh': 'D003913'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1208, 'end': 1219, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 1220, 'end': 1229, 'mesh': 'D002375'}, {'text': 'ergometrine', 'type': 'Chemical', 'start': 1231, 'end': 1242, 'mesh': 'D004874'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 1268, 'end': 1278, 'mesh': 'D005473'}, {'text': 'Trazodone', 'type': 'Chemical', 'start': 1305, 'end': 1314, 'mesh': 'D014196'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 1351, 'end': 1360, 'mesh': 'D002375'}, {'text': 'apomorphine', 'type': 'Chemical', 'start': 1377, 'end': 1388, 'mesh': 'D001058'}, {'text': 'dexamphetamine', 'type': 'Chemical', 'start': 1393, 'end': 1407, 'mesh': 'D003913'}, {'text': 'trazodone', 'type': 'Chemical', 'start': 1461, 'end': 1470, 'mesh': 'D014196'}, {'text': 'trazodone', 'type': 'Chemical', 'start': 1664, 'end': 1673, 'mesh': 'D014196'}, {'text': '5-HT', 'type': 'Chemical', 'start': 1681, 'end': 1685, 'mesh': 'D012701'}, {'text': '5-HT', 'type': 'Chemical', 'start': 1693, 'end': 1697, 'mesh': 'D012701'}, {'text': 'trazodone', 'type': 'Chemical', 'start': 1728, 'end': 1737, 'mesh': 'D014196'}, {'text': '5-HT', 'type': 'Chemical', 'start': 1776, 'end': 1780, 'mesh': 'D012701'}, {'text': '5-HT', 'type': 'Chemical', 'start': 1870, 'end': 1874, 'mesh': 'D012701'}, {'text': 'dexamphetamine', 'type': 'Chemical', 'start': 1900, 'end': 1914, 'mesh': 'D003913'}, {'text': 'haloperidol', 'type': 'Chemical', 'start': 1942, 'end': 1953, 'mesh': 'D006220'}, {'text': 'catalepsy', 'type': 'Disease', 'start': 1954, 'end': 1963, 'mesh': 'D002375'}]"
+1396,15625689,Swallowing abnormalities and dyskinesia in Parkinson's disease.,"Gastrointestinal abnormalities in Parkinson's disease (PD) have been known for almost two centuries, but many aspects concerning their pathophysiology have not been completely clarified. The aim of this study was to characterize the oropharyngeal dynamics in PD patients with and without levodopa-induced dyskinesia. Fifteen dyskinetic, 12 nondyskinetic patients, and a control group were included. Patients were asked about dysphagia and evaluated with the Unified Parkinson's Disease Rating Scale Parts II and III and the Hoehn and Yahr scale. Deglutition was assessed using modified barium swallow with videofluoroscopy. Nondyskinetic patients, but not the dyskinetic ones, showed less oropharyngeal swallowing efficiency (OPSE) for liquid food than controls (Dunnett, P = 0.02). Dyskinetic patients tended to have a greater OPSE than nondyskinetic (Dunnett, P = 0.06). Patients who were using a higher dose of levodopa had a greater OPSE and a trend toward a smaller oral transit time (Pearson's correlation, P = 0.01 and 0.08, respectively). Neither the report of dysphagia nor any of the PD severity parameters correlated to the videofluoroscopic variables. In the current study, dyskinetic patients performed better in swallowing function, which could be explained on the basis of a greater levodopa dose. Our results suggest a role for levodopa in the oral phase of deglutition and confirm that dysphagia is not a good predictor of deglutition alterations in PD.","[{'text': 'Swallowing abnormalities', 'type': 'Disease', 'start': 0, 'end': 24, 'mesh': 'D020447'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 29, 'end': 39, 'mesh': 'D004409'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 43, 'end': 62, 'mesh': 'D010300'}, {'text': 'Gastrointestinal abnormalities', 'type': 'Disease', 'start': 64, 'end': 94, 'mesh': 'D005767'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 98, 'end': 117, 'mesh': 'D010300'}, {'text': 'PD', 'type': 'Disease', 'start': 119, 'end': 121, 'mesh': 'D010300'}, {'text': 'PD', 'type': 'Disease', 'start': 323, 'end': 325, 'mesh': 'D010300'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 352, 'end': 360, 'mesh': 'D007980'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 369, 'end': 379, 'mesh': 'D004409'}, {'text': 'dyskinetic', 'type': 'Disease', 'start': 389, 'end': 399, 'mesh': 'D004409'}, {'text': 'dysphagia', 'type': 'Disease', 'start': 489, 'end': 498, 'mesh': 'D003680'}, {'text': ""Parkinson's Disease"", 'type': 'Disease', 'start': 530, 'end': 549, 'mesh': 'D010300'}, {'text': 'barium', 'type': 'Chemical', 'start': 650, 'end': 656, 'mesh': 'D001464'}, {'text': 'dyskinetic', 'type': 'Disease', 'start': 724, 'end': 734, 'mesh': 'D004409'}, {'text': 'Dyskinetic', 'type': 'Disease', 'start': 847, 'end': 857, 'mesh': 'D004409'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 978, 'end': 986, 'mesh': 'D007980'}, {'text': 'dysphagia', 'type': 'Disease', 'start': 1133, 'end': 1142, 'mesh': 'D003680'}, {'text': 'PD', 'type': 'Disease', 'start': 1158, 'end': 1160, 'mesh': 'D010300'}, {'text': 'dyskinetic', 'type': 'Disease', 'start': 1250, 'end': 1260, 'mesh': 'D004409'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1362, 'end': 1370, 'mesh': 'D007980'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1408, 'end': 1416, 'mesh': 'D007980'}, {'text': 'dysphagia', 'type': 'Disease', 'start': 1467, 'end': 1476, 'mesh': 'D003680'}, {'text': 'PD', 'type': 'Disease', 'start': 1531, 'end': 1533, 'mesh': 'D010300'}]"
+1397,15627798,Inhibition of nuclear factor-kappaB activation attenuates tubulointerstitial nephritis induced by gentamicin.,"BACKGROUND: Animals treated with gentamicin can show residual areas of interstitial fibrosis in the renal cortex. This study investigated the expression of nuclear factor-kappaB (NF-kappaB), mitogen-activated protein (MAP) kinases and macrophages in the renal cortex and structural and functional renal changes of rats treated with gentamicin or gentamicin + pyrrolidine dithiocarbamate (PDTC), an NF-kappaB inhibitor. METHODS: 38 female Wistar rats were injected with gentamicin, 40 mg/kg, twice a day for 9 days, 38 with gentamicin + PDTC, and 28 with 0.15 M NaCl solution. The animals were killed 5 and 30 days after these injections and the kidneys were removed for histological and immunohistochemical studies. The results of the immunohistochemical studies were scored according to the extent of staining. The fractional interstitial area was determined by morphometry. RESULTS: Gentamicin-treated rats presented a transitory increase in plasma creatinine levels. Increased ED-1, MAP kinases and NF-kappaB staining were also observed in the renal cortex from all gentamicin-treated rats compared to control (p < 0.05). The animals killed on day 30 also presented fibrosis in the renal cortex despite the recovery of renal function. Treatment with PDTC reduced the functional and structural changes induced by gentamicin. CONCLUSIONS: These data show that inhibition of NF-kappaB activation attenuates tubulointerstitial nephritis induced by gentamicin.","[{'text': 'tubulointerstitial nephritis', 'type': 'Disease', 'start': 58, 'end': 86, 'mesh': 'D009395'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 98, 'end': 108, 'mesh': 'D005839'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 143, 'end': 153, 'mesh': 'D005839'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 194, 'end': 202, 'mesh': 'D005355'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 442, 'end': 452, 'mesh': 'D005839'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 456, 'end': 466, 'mesh': 'D005839'}, {'text': 'pyrrolidine dithiocarbamate', 'type': 'Chemical', 'start': 469, 'end': 496, 'mesh': 'C020972'}, {'text': 'PDTC', 'type': 'Chemical', 'start': 498, 'end': 502, 'mesh': 'C020972'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 579, 'end': 589, 'mesh': 'D005839'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 633, 'end': 643, 'mesh': 'D005839'}, {'text': 'PDTC', 'type': 'Chemical', 'start': 646, 'end': 650, 'mesh': 'C020972'}, {'text': 'NaCl', 'type': 'Chemical', 'start': 671, 'end': 675, 'mesh': 'D012965'}, {'text': 'Gentamicin', 'type': 'Chemical', 'start': 995, 'end': 1005, 'mesh': 'D005839'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1061, 'end': 1071, 'mesh': 'D003404'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 1179, 'end': 1189, 'mesh': 'D005839'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 1279, 'end': 1287, 'mesh': 'D005355'}, {'text': 'PDTC', 'type': 'Chemical', 'start': 1363, 'end': 1367, 'mesh': 'C020972'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 1425, 'end': 1435, 'mesh': 'D005839'}, {'text': 'tubulointerstitial nephritis', 'type': 'Disease', 'start': 1517, 'end': 1545, 'mesh': 'D009395'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 1557, 'end': 1567, 'mesh': 'D005839'}]"
+1398,15630069,Glucose metabolism in patients with schizophrenia treated with atypical antipsychotic agents: a frequently sampled intravenous glucose tolerance test and minimal model analysis.,"BACKGROUND: While the incidence of new-onset diabetes mellitus may be increasing in patients with schizophrenia treated with certain atypical antipsychotic agents, it remains unclear whether atypical agents are directly affecting glucose metabolism or simply increasing known risk factors for diabetes. OBJECTIVE: To study the 2 drugs most clearly implicated (clozapine and olanzapine) and risperidone using a frequently sampled intravenous glucose tolerance test. DESIGN: A cross-sectional design in stable, treated patients with schizophrenia evaluated using a frequently sampled intravenous glucose tolerance test and the Bergman minimal model analysis. SETTING: Subjects were recruited from an urban community mental health clinic and were studied at a general clinical research center. Patients Fifty subjects signed informed consent and 41 underwent the frequently sampled intravenous glucose tolerance test. Thirty-six nonobese subjects with schizophrenia or schizoaffective disorder, matched by body mass index and treated with either clozapine, olanzapine, or risperidone, were included in the analysis. MAIN OUTCOME MEASURES: Fasting plasma glucose and fasting serum insulin levels, insulin sensitivity index, homeostasis model assessment of insulin resistance, and glucose effectiveness. RESULTS: The mean +/- SD duration of treatment with the identified atypical antipsychotic agent was 68.3 +/- 28.9 months (clozapine), 29.5 +/- 17.5 months (olanzapine), and 40.9 +/- 33.7 (risperidone). Fasting serum insulin concentrations differed among groups (F(33) = 3.35; P = .047) (clozapine>olanzapine>risperidone) with significant differences between clozapine and risperidone (t(33) = 2.32; P = .03) and olanzapine and risperidone (t(33) = 2.15; P = .04). There was a significant difference in insulin sensitivity index among groups (F(33) = 10.66; P<.001) (clozapine<olanzapine<risperidone), with subjects who received clozapine and olanzapine exhibiting significant insulin resistance compared with subjects who were treated with risperidone (clozapine vs risperidone, t(33) = -4.29; P<.001; olanzapine vs risperidone, t(33) = -3.62; P = .001 [P<.001]). The homeostasis model assessment of insulin resistance also differed significantly among groups (F(33) = 4.92; P = .01) (clozapine>olanzapine>risperidone) (clozapine vs risperidone, t(33) = 2.94; P = .006; olanzapine vs risperidone, t(33) = 2.42; P = .02). There was a significant difference among groups in glucose effectiveness (F(30) = 4.18; P = .02) (clozapine<olanzapine<risperidone) with significant differences between clozapine and risperidone (t(30) = -2.59; P = .02) and olanzapine and risperidone (t(30) = -2.34, P = .03). CONCLUSIONS: Both nonobese clozapine- and olanzapine-treated groups displayed significant insulin resistance and impairment of glucose effectiveness compared with risperidone-treated subjects. Patients taking clozapine and olanzapine must be examined for insulin resistance and its consequences.","[{'text': 'Glucose', 'type': 'Chemical', 'start': 0, 'end': 7, 'mesh': 'D005947'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 36, 'end': 49, 'mesh': 'D012559'}, {'text': 'glucose', 'type': 'Chemical', 'start': 127, 'end': 134, 'mesh': 'D005947'}, {'text': 'diabetes mellitus', 'type': 'Disease', 'start': 223, 'end': 240, 'mesh': 'D003920'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 276, 'end': 289, 'mesh': 'D012559'}, {'text': 'glucose', 'type': 'Chemical', 'start': 408, 'end': 415, 'mesh': 'D005947'}, {'text': 'diabetes', 'type': 'Disease', 'start': 471, 'end': 479, 'mesh': 'D003920'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 538, 'end': 547, 'mesh': 'D003024'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 552, 'end': 562, 'mesh': 'C076029'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 568, 'end': 579, 'mesh': 'D018967'}, {'text': 'glucose', 'type': 'Chemical', 'start': 619, 'end': 626, 'mesh': 'D005947'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 709, 'end': 722, 'mesh': 'D012559'}, {'text': 'glucose', 'type': 'Chemical', 'start': 772, 'end': 779, 'mesh': 'D005947'}, {'text': 'glucose', 'type': 'Chemical', 'start': 1069, 'end': 1076, 'mesh': 'D005947'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 1127, 'end': 1140, 'mesh': 'D012559'}, {'text': 'schizoaffective disorder', 'type': 'Disease', 'start': 1144, 'end': 1168, 'mesh': 'D011618'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 1221, 'end': 1230, 'mesh': 'D003024'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 1232, 'end': 1242, 'mesh': 'C076029'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 1247, 'end': 1258, 'mesh': 'D018967'}, {'text': 'glucose', 'type': 'Chemical', 'start': 1329, 'end': 1336, 'mesh': 'D005947'}, {'text': 'insulin sensitivity', 'type': 'Disease', 'start': 1371, 'end': 1390, 'mesh': 'D007333'}, {'text': 'insulin resistance', 'type': 'Disease', 'start': 1430, 'end': 1448, 'mesh': 'D007333'}, {'text': 'glucose', 'type': 'Chemical', 'start': 1454, 'end': 1461, 'mesh': 'D005947'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 1599, 'end': 1608, 'mesh': 'D003024'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 1633, 'end': 1643, 'mesh': 'C076029'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 1665, 'end': 1676, 'mesh': 'D018967'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 1764, 'end': 1773, 'mesh': 'D003024'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 1774, 'end': 1784, 'mesh': 'C076029'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 1785, 'end': 1796, 'mesh': 'D018967'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 1835, 'end': 1844, 'mesh': 'D003024'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 1849, 'end': 1860, 'mesh': 'D018967'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 1889, 'end': 1899, 'mesh': 'C076029'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 1904, 'end': 1915, 'mesh': 'D018967'}, {'text': 'insulin sensitivity', 'type': 'Disease', 'start': 1979, 'end': 1998, 'mesh': 'D007333'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 2043, 'end': 2052, 'mesh': 'D003024'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 2053, 'end': 2063, 'mesh': 'C076029'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 2064, 'end': 2075, 'mesh': 'D018967'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 2105, 'end': 2114, 'mesh': 'D003024'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 2119, 'end': 2129, 'mesh': 'C076029'}, {'text': 'insulin resistance', 'type': 'Disease', 'start': 2153, 'end': 2171, 'mesh': 'D007333'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 2217, 'end': 2228, 'mesh': 'D018967'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 2230, 'end': 2239, 'mesh': 'D003024'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 2243, 'end': 2254, 'mesh': 'D018967'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 2279, 'end': 2289, 'mesh': 'C076029'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 2293, 'end': 2304, 'mesh': 'D018967'}, {'text': 'insulin resistance', 'type': 'Disease', 'start': 2377, 'end': 2395, 'mesh': 'D007333'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 2462, 'end': 2471, 'mesh': 'D003024'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 2472, 'end': 2482, 'mesh': 'C076029'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 2483, 'end': 2494, 'mesh': 'D018967'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 2497, 'end': 2506, 'mesh': 'D003024'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 2510, 'end': 2521, 'mesh': 'D018967'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 2547, 'end': 2557, 'mesh': 'C076029'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 2561, 'end': 2572, 'mesh': 'D018967'}, {'text': 'glucose', 'type': 'Chemical', 'start': 2649, 'end': 2656, 'mesh': 'D005947'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 2696, 'end': 2705, 'mesh': 'D003024'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 2706, 'end': 2716, 'mesh': 'C076029'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 2717, 'end': 2728, 'mesh': 'D018967'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 2767, 'end': 2776, 'mesh': 'D003024'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 2781, 'end': 2792, 'mesh': 'D018967'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 2822, 'end': 2832, 'mesh': 'C076029'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 2837, 'end': 2848, 'mesh': 'D018967'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 2902, 'end': 2911, 'mesh': 'D003024'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 2917, 'end': 2927, 'mesh': 'C076029'}, {'text': 'insulin resistance', 'type': 'Disease', 'start': 2965, 'end': 2983, 'mesh': 'D007333'}, {'text': 'glucose', 'type': 'Chemical', 'start': 3002, 'end': 3009, 'mesh': 'D005947'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 3038, 'end': 3049, 'mesh': 'D018967'}, {'text': 'clozapine', 'type': 'Chemical', 'start': 3084, 'end': 3093, 'mesh': 'D003024'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 3098, 'end': 3108, 'mesh': 'C076029'}, {'text': 'insulin resistance', 'type': 'Disease', 'start': 3130, 'end': 3148, 'mesh': 'D007333'}]"
+1399,15815446,Focal cerebral ischemia in rats: effect of phenylephrine-induced hypertension during reperfusion.,"After 180 min of temporary middle cerebral artery occlusion in spontaneously hypertensive rats, the effect of phenylephrine-induced hypertension on ischemic brain injury and blood-brain barrier permeability was determined. Blood pressure was manipulated by one of the following schedules during 120 min of reperfusion: Control, normotensive reperfusion; 90/hypertension (90/HTN), blood pressure was increased by 35 mm Hg during the initial 90 min of reperfusion only; 15/hypertension (15/HTN), normotensive reperfusion for 30 min followed by 15 min of hypertension and 75 min of normotension. Part A, for eight rats in each group brain injury was evaluated by staining tissue using 2,3,5-triphenyltetrazolium chloride and edema was evaluated by microgravimetry. Part B, for eight different rats in each group blood-brain barrier permeability was evaluated by measuring the amount and extent of extravasation of Evans Blue dye. Brain injury (percentage of the ischemic hemisphere) was less in the 15/HTN group (16 +/- 6, mean +/- SD) versus the 90/HTN group (30 +/- 6), which was in turn less than the control group (42 +/- 5). Specific gravity was greater in the 15/HTN group (1.043 +/- 0.002) versus the 90/HTN (1.036 +/- 0.003) and control (1.037 +/- 0.003) groups. Evans Blue (mug g-1 of brain tissue) was greater in the 90/HTN group (24.4 +/- 6.0) versus the control group (12.3 +/- 4.1), which was in turn greater than the 15/HTN group (7.3 +/- 3.2). This study supports a hypothesis that during reperfusion, a short interval of hypertension decreases brain injury and edema; and that sustained hypertension increases the risk of vasogenic edema.","[{'text': 'cerebral ischemia', 'type': 'Disease', 'start': 6, 'end': 23, 'mesh': 'D002545'}, {'text': 'phenylephrine', 'type': 'Chemical', 'start': 43, 'end': 56, 'mesh': 'D010656'}, {'text': 'hypertension', 'type': 'Disease', 'start': 65, 'end': 77, 'mesh': 'D006973'}, {'text': 'middle cerebral artery occlusion', 'type': 'Disease', 'start': 125, 'end': 157, 'mesh': 'D020244'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 175, 'end': 187, 'mesh': 'D006973'}, {'text': 'phenylephrine', 'type': 'Chemical', 'start': 208, 'end': 221, 'mesh': 'D010656'}, {'text': 'hypertension', 'type': 'Disease', 'start': 230, 'end': 242, 'mesh': 'D006973'}, {'text': 'ischemic brain injury', 'type': 'Disease', 'start': 246, 'end': 267, 'mesh': 'D001930'}, {'text': 'hypertension', 'type': 'Disease', 'start': 455, 'end': 467, 'mesh': 'D006973'}, {'text': 'HTN', 'type': 'Disease', 'start': 472, 'end': 475, 'mesh': 'D006973'}, {'text': 'hypertension', 'type': 'Disease', 'start': 569, 'end': 581, 'mesh': 'D006973'}, {'text': 'HTN', 'type': 'Disease', 'start': 586, 'end': 589, 'mesh': 'D006973'}, {'text': 'hypertension', 'type': 'Disease', 'start': 650, 'end': 662, 'mesh': 'D006973'}, {'text': 'brain injury', 'type': 'Disease', 'start': 728, 'end': 740, 'mesh': 'D001930'}, {'text': '2,3,5-triphenyltetrazolium chloride', 'type': 'Chemical', 'start': 780, 'end': 815, 'mesh': 'C009591'}, {'text': 'edema', 'type': 'Disease', 'start': 820, 'end': 825, 'mesh': 'D004487'}, {'text': 'Brain injury', 'type': 'Disease', 'start': 1025, 'end': 1037, 'mesh': 'D001930'}, {'text': 'ischemic hemisphere', 'type': 'Disease', 'start': 1057, 'end': 1076, 'mesh': 'D002545'}, {'text': 'HTN', 'type': 'Disease', 'start': 1097, 'end': 1100, 'mesh': 'D006973'}, {'text': 'HTN', 'type': 'Disease', 'start': 1145, 'end': 1148, 'mesh': 'D006973'}, {'text': 'HTN', 'type': 'Disease', 'start': 1264, 'end': 1267, 'mesh': 'D006973'}, {'text': 'HTN', 'type': 'Disease', 'start': 1306, 'end': 1309, 'mesh': 'D006973'}, {'text': 'Evans Blue', 'type': 'Chemical', 'start': 1366, 'end': 1376, 'mesh': 'D005070'}, {'text': 'HTN', 'type': 'Disease', 'start': 1425, 'end': 1428, 'mesh': 'D006973'}, {'text': 'HTN', 'type': 'Disease', 'start': 1529, 'end': 1532, 'mesh': 'D006973'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1632, 'end': 1644, 'mesh': 'D006973'}, {'text': 'brain injury', 'type': 'Disease', 'start': 1655, 'end': 1667, 'mesh': 'D001930'}, {'text': 'edema', 'type': 'Disease', 'start': 1672, 'end': 1677, 'mesh': 'D004487'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1698, 'end': 1710, 'mesh': 'D006973'}, {'text': 'vasogenic edema', 'type': 'Disease', 'start': 1733, 'end': 1748, 'mesh': 'D001929'}]"
+1400,15817013,People aged over 75 in atrial fibrillation on warfarin: the rate of major hemorrhage and stroke in more than 500 patient-years of follow-up.,"OBJECTIVES: To determine the incidence of major hemorrhage and stroke in people aged 76 and older with atrial fibrillation on adjusted-dose warfarin who had been recently been admitted to hospital. DESIGN: A retrospective observational cohort study. SETTING: A major healthcare network involving four tertiary hospitals. PARTICIPANTS: Two hundred thirty-five patients aged 76 and older admitted to a major healthcare network between July 1, 2001, and June 30, 2002, with atrial fibrillation on warfarin were enrolled. MEASUREMENTS: Information regarding major bleeding episodes, strokes, and warfarin use was obtained from patients, relatives, primary physicians, and medical records. RESULTS: Two hundred twenty-eight patients (42% men) with a mean age of 81.1 (range 76-94) were included in the analysis. Total follow-up on warfarin was 530 years (mean 28 months). There were 53 major hemorrhages, for an annual rate of 10.0%, including 24 (45.3%) life-threatening and five (9.4%) fatal bleeds. The annual stroke rate after initiation of warfarin was 2.6%. CONCLUSION: The rate of major hemorrhage was high in this old, frail group, but excluding fatalities, resulted in no long-term sequelae, and the stroke rate on warfarin was low, demonstrating how effective warfarin treatment is.","[{'text': 'atrial fibrillation', 'type': 'Disease', 'start': 23, 'end': 42, 'mesh': 'D001281'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 46, 'end': 54, 'mesh': 'D014859'}, {'text': 'hemorrhage', 'type': 'Disease', 'start': 74, 'end': 84, 'mesh': 'D006470'}, {'text': 'stroke', 'type': 'Disease', 'start': 89, 'end': 95, 'mesh': 'D020521'}, {'text': 'hemorrhage', 'type': 'Disease', 'start': 189, 'end': 199, 'mesh': 'D006470'}, {'text': 'stroke', 'type': 'Disease', 'start': 204, 'end': 210, 'mesh': 'D020521'}, {'text': 'atrial fibrillation', 'type': 'Disease', 'start': 244, 'end': 263, 'mesh': 'D001281'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 281, 'end': 289, 'mesh': 'D014859'}, {'text': 'atrial fibrillation', 'type': 'Disease', 'start': 612, 'end': 631, 'mesh': 'D001281'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 635, 'end': 643, 'mesh': 'D014859'}, {'text': 'bleeding', 'type': 'Disease', 'start': 701, 'end': 709, 'mesh': 'D006470'}, {'text': 'strokes', 'type': 'Disease', 'start': 720, 'end': 727, 'mesh': 'D020521'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 733, 'end': 741, 'mesh': 'D014859'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 967, 'end': 975, 'mesh': 'D014859'}, {'text': 'hemorrhages', 'type': 'Disease', 'start': 1028, 'end': 1039, 'mesh': 'D006470'}, {'text': 'stroke', 'type': 'Disease', 'start': 1149, 'end': 1155, 'mesh': 'D020521'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 1181, 'end': 1189, 'mesh': 'D014859'}, {'text': 'hemorrhage', 'type': 'Disease', 'start': 1230, 'end': 1240, 'mesh': 'D006470'}, {'text': 'stroke', 'type': 'Disease', 'start': 1345, 'end': 1351, 'mesh': 'D020521'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 1360, 'end': 1368, 'mesh': 'D014859'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 1406, 'end': 1414, 'mesh': 'D014859'}]"
+1401,15859361,Safety of celecoxib in patients with adverse skin reactions to acetaminophen (paracetamol) and nimesulide associated or not with common non-steroidal anti-inflammatory drugs.,"BACKGROUND: Acetaminophen (paracetamol--P) and Nimesulide (N) are widely used analgesic-antipyretic/anti-inflammatory drugs. The rate of adverse hypersensitivity reactions to these agents is generally low. On the contrary non-steroidal anti-inflammatory drugs (NSAIDs) are commonly involved in such reactions. Celecoxib (CE) is a novel drug, with high selectivity and affinity for COX-2 enzyme. OBJECTIVE: We evaluated the tolerability of CE in a group of patients with documented history of adverse cutaneous reactions to P and N associated or not to classic NSAIDs. METHODS: We studied 9 patients with hypersensitivity to P and N with or without associated reactions to classic NSAIDs. The diagnosis of P and N-induced skin reactions was based in vivo challenge. The placebo was blindly administered at the beginning of each challenge. After three days, a cumulative dosage of 200 mg of CE in refracted doses were given. After 2-3 days, a single dose of 200 mg was administered. All patients were observed for 6 hours after each challenge, and controlled again after 24 hours to exclude delayed reactions. The challenge was considered positive if one or more of the following appeared: erythema, rush or urticaria-angioedema. RESULTS: No reaction was observed with placebo and eight patients (88.8%) tolerated CE. Only one patient developed a moderate angioedema of the lips. CONCLUSION: Only one hypersensitivity reaction to CE was documented among 9 P and N-highly NSAIDs intolerant patients. Thus, we conclude that CE is a reasonably safe alternative to be used in subjects who do not tolerate P and N.","[{'text': 'celecoxib', 'type': 'Chemical', 'start': 10, 'end': 19, 'mesh': 'C105934'}, {'text': 'skin reactions', 'type': 'Disease', 'start': 45, 'end': 59, 'mesh': 'D003875'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 63, 'end': 76, 'mesh': 'D000082'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 78, 'end': 89, 'mesh': 'D000082'}, {'text': 'nimesulide', 'type': 'Chemical', 'start': 95, 'end': 105, 'mesh': 'C012655'}, {'text': 'Acetaminophen', 'type': 'Chemical', 'start': 187, 'end': 200, 'mesh': 'D000082'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 202, 'end': 213, 'mesh': 'D000082'}, {'text': 'P', 'type': 'Chemical', 'start': 215, 'end': 216, 'mesh': 'D000082'}, {'text': 'Nimesulide', 'type': 'Chemical', 'start': 222, 'end': 232, 'mesh': 'C012655'}, {'text': 'N', 'type': 'Chemical', 'start': 234, 'end': 235, 'mesh': 'C012655'}, {'text': 'hypersensitivity', 'type': 'Disease', 'start': 320, 'end': 336, 'mesh': 'D004342'}, {'text': 'Celecoxib', 'type': 'Chemical', 'start': 485, 'end': 494, 'mesh': 'C105934'}, {'text': 'CE', 'type': 'Chemical', 'start': 496, 'end': 498, 'mesh': 'C105934'}, {'text': 'CE', 'type': 'Chemical', 'start': 614, 'end': 616, 'mesh': 'C105934'}, {'text': 'cutaneous reactions', 'type': 'Disease', 'start': 675, 'end': 694, 'mesh': 'D003875'}, {'text': 'P', 'type': 'Chemical', 'start': 698, 'end': 699, 'mesh': 'D000082'}, {'text': 'N', 'type': 'Chemical', 'start': 704, 'end': 705, 'mesh': 'C012655'}, {'text': 'hypersensitivity', 'type': 'Disease', 'start': 779, 'end': 795, 'mesh': 'D004342'}, {'text': 'P', 'type': 'Chemical', 'start': 799, 'end': 800, 'mesh': 'D000082'}, {'text': 'N', 'type': 'Chemical', 'start': 805, 'end': 806, 'mesh': 'C012655'}, {'text': 'P', 'type': 'Chemical', 'start': 880, 'end': 881, 'mesh': 'D000082'}, {'text': 'N', 'type': 'Chemical', 'start': 886, 'end': 887, 'mesh': 'C012655'}, {'text': 'skin reactions', 'type': 'Disease', 'start': 896, 'end': 910, 'mesh': 'D003875'}, {'text': 'CE', 'type': 'Chemical', 'start': 1064, 'end': 1066, 'mesh': 'C105934'}, {'text': 'erythema', 'type': 'Disease', 'start': 1363, 'end': 1371, 'mesh': 'D004890'}, {'text': 'urticaria', 'type': 'Disease', 'start': 1381, 'end': 1390, 'mesh': 'D014581'}, {'text': 'angioedema', 'type': 'Disease', 'start': 1391, 'end': 1401, 'mesh': 'D000799'}, {'text': 'CE', 'type': 'Chemical', 'start': 1487, 'end': 1489, 'mesh': 'C105934'}, {'text': 'angioedema', 'type': 'Disease', 'start': 1529, 'end': 1539, 'mesh': 'D000799'}, {'text': 'hypersensitivity', 'type': 'Disease', 'start': 1574, 'end': 1590, 'mesh': 'D004342'}, {'text': 'CE', 'type': 'Chemical', 'start': 1603, 'end': 1605, 'mesh': 'C105934'}, {'text': 'P', 'type': 'Chemical', 'start': 1629, 'end': 1630, 'mesh': 'D000082'}, {'text': 'N', 'type': 'Chemical', 'start': 1635, 'end': 1636, 'mesh': 'C012655'}, {'text': 'CE', 'type': 'Chemical', 'start': 1695, 'end': 1697, 'mesh': 'C105934'}, {'text': 'P', 'type': 'Chemical', 'start': 1774, 'end': 1775, 'mesh': 'D000082'}, {'text': 'N', 'type': 'Chemical', 'start': 1780, 'end': 1781, 'mesh': 'C012655'}]"
+1402,15882284,Case-control study of regular analgesic and nonsteroidal anti-inflammatory use and end-stage renal disease.,"BACKGROUND: Studies on the association between the long-term use of aspirin and other analgesic and nonsteroidal anti-inflammatory drugs (NSAIDs) and end-stage renal disease (ESRD) have given conflicting results. In order to examine this association, a case-control study with incident cases of ESRD was carried out. METHODS: The cases were all patients entering the local dialysis program because of ESRD in the study area between June 1, 1995 and November 30, 1997. They were classified according to the underlying disease, which had presumably led them to ESRD. Controls were patients admitted to the same hospitals from where the cases arose, also matched by age and sex. Odds ratios were calculated using a conditional logistic model, including potential confounding factors, both for the whole study population and for the various underlying diseases. RESULTS: Five hundred and eighty-three cases and 1190 controls were included in the analysis. Long-term use of any analgesic was associated with an overall odds ratio of 1.22 (95% CI, 0.89-1.66). For specific groups of drugs, the risks were 1.56 (1.05-2.30) for aspirin, 1.03 (0.60-1.76) for pyrazolones, 0.80 (0.39-1.63) for paracetamol, and 0.94 (0.57-1.56) for nonaspirin NSAIDs. The risk of ESRD associated with aspirin was related to the cumulated dose and duration of use, and it was particularly high among the subset of patients with vascular nephropathy as underlying disease [2.35 (1.17-4.72)]. CONCLUSION: Our data indicate that long-term use of nonaspirin analgesic drugs and NSAIDs is not associated with an increased risk of ESRD. However, the chronic use of aspirin may increase the risk of ESRD.","[{'text': 'end-stage renal disease', 'type': 'Disease', 'start': 83, 'end': 106, 'mesh': 'D007676'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 176, 'end': 183, 'mesh': 'D001241'}, {'text': 'end-stage renal disease', 'type': 'Disease', 'start': 258, 'end': 281, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 283, 'end': 287, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 403, 'end': 407, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 509, 'end': 513, 'mesh': 'D007676'}, {'text': 'ESRD', 'type': 'Disease', 'start': 667, 'end': 671, 'mesh': 'D007676'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1228, 'end': 1235, 'mesh': 'D001241'}, {'text': 'pyrazolones', 'type': 'Chemical', 'start': 1258, 'end': 1269, 'mesh': 'D047069'}, {'text': 'paracetamol', 'type': 'Chemical', 'start': 1292, 'end': 1303, 'mesh': 'D000082'}, {'text': 'ESRD', 'type': 'Disease', 'start': 1361, 'end': 1365, 'mesh': 'D007676'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1382, 'end': 1389, 'mesh': 'D001241'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1517, 'end': 1528, 'mesh': 'D007674'}, {'text': 'ESRD', 'type': 'Disease', 'start': 1705, 'end': 1709, 'mesh': 'D007676'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1739, 'end': 1746, 'mesh': 'D001241'}, {'text': 'ESRD', 'type': 'Disease', 'start': 1772, 'end': 1776, 'mesh': 'D007676'}]"
+1403,15953230,Two cases of amisulpride overdose: a cause for prolonged QT syndrome.,"Two cases of deliberate self-poisoning with 5 g and 3.6 g of amisulpride, respectively, are reported. In both cases, QT prolongation and hypocalcaemia were noted. The QT prolongation appeared to respond to administration of i.v. calcium gluconate.","[{'text': 'amisulpride', 'type': 'Chemical', 'start': 13, 'end': 24, 'mesh': 'C012052'}, {'text': 'overdose', 'type': 'Disease', 'start': 25, 'end': 33, 'mesh': 'D062787'}, {'text': 'prolonged QT syndrome', 'type': 'Disease', 'start': 47, 'end': 68, 'mesh': 'D008133'}, {'text': 'poisoning', 'type': 'Disease', 'start': 99, 'end': 108, 'mesh': 'D011041'}, {'text': 'amisulpride', 'type': 'Chemical', 'start': 131, 'end': 142, 'mesh': 'C012052'}, {'text': 'QT prolongation', 'type': 'Disease', 'start': 187, 'end': 202, 'mesh': 'D008133'}, {'text': 'hypocalcaemia', 'type': 'Disease', 'start': 207, 'end': 220, 'mesh': 'D006996'}, {'text': 'QT prolongation', 'type': 'Disease', 'start': 237, 'end': 252, 'mesh': 'D008133'}, {'text': 'calcium gluconate', 'type': 'Chemical', 'start': 299, 'end': 316, 'mesh': 'D002125'}]"
+1404,15987266,Growth-associated protein 43 expression in hippocampal molecular layer of chronic epileptic rats treated with cycloheximide.,"PURPOSE: GAP43 has been thought to be linked with mossy fiber sprouting (MFS) in various experimental models of epilepsy. To investigate how GAP43 expression (GAP43-ir) correlates with MFS, we assessed the intensity (densitometry) and extension (width) of GAP43-ir in the inner molecular layer of the dentate gyrus (IML) of rats subject to status epilepticus induced by pilocarpine (Pilo), previously injected or not with cycloheximide (CHX), which has been shown to inhibit MFS. METHODS: CHX was injected before the Pilo injection in adult Wistar rats. The Pilo group was injected with the same drugs, except for CHX. Animals were killed between 30 and 60 days later, and brain sections were processed for GAP43 immunohistochemistry. RESULTS: Densitometry showed no significant difference regarding GAP43-ir in the IML between Pilo, CHX+Pilo, and control groups. However, the results of the width of the GAP43-ir band in the IML showed that CHX+Pilo and control animals had a significantly larger band (p = 0.03) as compared with that in the Pilo group. CONCLUSIONS: Our current finding that animals in the CHX+Pilo group have a GAP43-ir band in the IML, similar to that of controls, reinforces prior data on the blockade of MFS in these animals. The change in GAP43-ir present in Pilo-treated animals was a thinning of the band to a very narrow layer just above the granule cell layer that is likely to be associated with the loss of hilar cell projections that express GAP-43.","[{'text': 'epileptic', 'type': 'Disease', 'start': 82, 'end': 91, 'mesh': 'D004827'}, {'text': 'cycloheximide', 'type': 'Chemical', 'start': 110, 'end': 123, 'mesh': 'D003513'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 237, 'end': 245, 'mesh': 'D004827'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 465, 'end': 483, 'mesh': 'D013226'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 495, 'end': 506, 'mesh': 'D010862'}, {'text': 'Pilo', 'type': 'Chemical', 'start': 508, 'end': 512, 'mesh': 'D010862'}, {'text': 'cycloheximide', 'type': 'Chemical', 'start': 547, 'end': 560, 'mesh': 'D003513'}, {'text': 'CHX', 'type': 'Chemical', 'start': 562, 'end': 565, 'mesh': 'D003513'}, {'text': 'CHX', 'type': 'Chemical', 'start': 614, 'end': 617, 'mesh': 'D003513'}, {'text': 'Pilo', 'type': 'Chemical', 'start': 642, 'end': 646, 'mesh': 'D010862'}, {'text': 'Pilo', 'type': 'Chemical', 'start': 683, 'end': 687, 'mesh': 'D010862'}, {'text': 'CHX', 'type': 'Chemical', 'start': 739, 'end': 742, 'mesh': 'D003513'}, {'text': 'Pilo', 'type': 'Chemical', 'start': 953, 'end': 957, 'mesh': 'D010862'}, {'text': 'CHX', 'type': 'Chemical', 'start': 959, 'end': 962, 'mesh': 'D003513'}, {'text': 'Pilo', 'type': 'Chemical', 'start': 963, 'end': 967, 'mesh': 'D010862'}, {'text': 'CHX', 'type': 'Chemical', 'start': 1067, 'end': 1070, 'mesh': 'D003513'}, {'text': 'Pilo', 'type': 'Chemical', 'start': 1071, 'end': 1075, 'mesh': 'D010862'}, {'text': 'Pilo', 'type': 'Chemical', 'start': 1168, 'end': 1172, 'mesh': 'D010862'}, {'text': 'CHX', 'type': 'Chemical', 'start': 1233, 'end': 1236, 'mesh': 'D003513'}, {'text': 'Pilo', 'type': 'Chemical', 'start': 1237, 'end': 1241, 'mesh': 'D010862'}, {'text': 'Pilo', 'type': 'Chemical', 'start': 1407, 'end': 1411, 'mesh': 'D010862'}]"
+1405,15991002,Nicotine antagonizes caffeine- but not pentylenetetrazole-induced anxiogenic effect in mice.,"RATIONALE: Nicotine and caffeine are widely consumed licit psychoactive drugs worldwide. Epidemiological studies showed that they were generally used concurrently. Although some studies in experimental animals indicate clear pharmacological interactions between them, no studies have shown a specific interaction on anxiety responses. OBJECTIVES: The present study investigates the effects of nicotine on anxiety induced by caffeine and another anxiogenic drug, pentylenetetrazole, in mice. The elevated plus-maze (EPM) test was used to evaluate the effects of drugs on anxiety. METHODS: Adult male Swiss Webster mice (25-32 g) were given nicotine (0.05-0.25 mg/kg s.c.) or saline 10 min before caffeine (70 mg/kg i.p.) or pentylenetetrazole (15 and 30 mg/kg i.p.) injections. After 15 min, mice were evaluated for their open- and closed-arm time and entries on the EPM for a 10-min session. Locomotor activity was recorded for individual groups by using the same treatment protocol with the EPM test. RESULTS: Nicotine (0.05-0.25 mg/kg) itself did not produce any significant effect in the EPM test, whereas caffeine (70 mg/kg) and pentylenetetrazole (30 mg/kg) produced an anxiogenic effect, apparent with decreases in open-arm time and entry. Nicotine (0.25 mg/kg) pretreatment blocked the caffeine- but not pentylenetetrazole-induced anxiety. Administration of each drug and their combinations did not produce any effect on locomotor activity. CONCLUSIONS: Our results suggest that the antagonistic effect of nicotine on caffeine-induced anxiety is specific to caffeine, instead of a non-specific anxiolytic effect. Thus, it may extend the current findings on the interaction between nicotine and caffeine.","[{'text': 'Nicotine', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D009538'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 21, 'end': 29, 'mesh': 'D002110'}, {'text': 'pentylenetetrazole', 'type': 'Chemical', 'start': 39, 'end': 57, 'mesh': 'D010433'}, {'text': 'Nicotine', 'type': 'Chemical', 'start': 104, 'end': 112, 'mesh': 'D009538'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 117, 'end': 125, 'mesh': 'D002110'}, {'text': 'anxiety', 'type': 'Disease', 'start': 409, 'end': 416, 'mesh': 'D001008'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 486, 'end': 494, 'mesh': 'D009538'}, {'text': 'anxiety', 'type': 'Disease', 'start': 498, 'end': 505, 'mesh': 'D001008'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 517, 'end': 525, 'mesh': 'D002110'}, {'text': 'pentylenetetrazole', 'type': 'Chemical', 'start': 555, 'end': 573, 'mesh': 'D010433'}, {'text': 'anxiety', 'type': 'Disease', 'start': 663, 'end': 670, 'mesh': 'D001008'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 732, 'end': 740, 'mesh': 'D009538'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 788, 'end': 796, 'mesh': 'D002110'}, {'text': 'pentylenetetrazole', 'type': 'Chemical', 'start': 816, 'end': 834, 'mesh': 'D010433'}, {'text': 'Nicotine', 'type': 'Chemical', 'start': 1104, 'end': 1112, 'mesh': 'D009538'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1202, 'end': 1210, 'mesh': 'D002110'}, {'text': 'pentylenetetrazole', 'type': 'Chemical', 'start': 1226, 'end': 1244, 'mesh': 'D010433'}, {'text': 'Nicotine', 'type': 'Chemical', 'start': 1339, 'end': 1347, 'mesh': 'D009538'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1386, 'end': 1394, 'mesh': 'D002110'}, {'text': 'pentylenetetrazole', 'type': 'Chemical', 'start': 1404, 'end': 1422, 'mesh': 'D010433'}, {'text': 'anxiety', 'type': 'Disease', 'start': 1431, 'end': 1438, 'mesh': 'D001008'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 1606, 'end': 1614, 'mesh': 'D009538'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1618, 'end': 1626, 'mesh': 'D002110'}, {'text': 'anxiety', 'type': 'Disease', 'start': 1635, 'end': 1642, 'mesh': 'D001008'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1658, 'end': 1666, 'mesh': 'D002110'}, {'text': 'nicotine', 'type': 'Chemical', 'start': 1781, 'end': 1789, 'mesh': 'D009538'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1794, 'end': 1802, 'mesh': 'D002110'}]"
+1406,16034922,Long term hormone therapy for perimenopausal and postmenopausal women.,"BACKGROUND: Hormone therapy (HT) is widely used for controlling menopausal symptoms. It has also been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women but the evidence supporting its use for these indications is largely observational. OBJECTIVES: To assess the effect of long-term HT on mortality, heart disease, venous thromboembolism, stroke, transient ischaemic attacks, breast cancer, colorectal cancer, ovarian cancer, endometrial cancer, gallbladder disease, cognitive function, dementia, fractures and quality of life. SEARCH STRATEGY: We searched the following databases up to November 2004: the Cochrane Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Biological Abstracts. Relevant non-indexed journals and conference abstracts were also searched. SELECTION CRITERIA: Randomised double-blind trials of HT (oestrogens with or without progestogens) versus placebo, taken for at least one year by perimenopausal or postmenopausal women. DATA COLLECTION AND ANALYSIS: Fifteen RCTs were included. Trials were assessed for quality and two review authors extracted data independently. They calculated risk ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. Clinical heterogeneity precluded meta-analysis for most outcomes. MAIN RESULTS: All the statistically significant results were derived from the two biggest trials. In relatively healthy women, combined continuous HT significantly increased the risk of venous thromboembolism or coronary event (after one year's use), stroke (after 3 years), breast cancer (after 5 years) and gallbladder disease. Long-term oestrogen-only HT also significantly increased the risk of stroke and gallbladder disease. Overall, the only statistically significant benefits of HT were a decreased incidence of fractures and colon cancer with long-term use. Among relatively healthy women over 65 years 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 thromboembolism. No trials focussed specifically on younger women. However, 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 thromboembolism in women taking combined continuous HT; their absolute risk remained very low. 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.","[{'text': 'menopausal symptoms', 'type': 'Disease', 'start': 135, 'end': 154, 'mesh': 'D008594'}, {'text': 'cardiovascular disease', 'type': 'Disease', 'start': 215, 'end': 237, 'mesh': 'D002318'}, {'text': 'osteoporosis', 'type': 'Disease', 'start': 239, 'end': 251, 'mesh': 'D010024'}, {'text': 'dementia', 'type': 'Disease', 'start': 256, 'end': 264, 'mesh': 'D003704'}, {'text': 'heart disease', 'type': 'Disease', 'start': 427, 'end': 440, 'mesh': 'D006331'}, {'text': 'venous thromboembolism', 'type': 'Disease', 'start': 442, 'end': 464, 'mesh': 'D054556'}, {'text': 'stroke', 'type': 'Disease', 'start': 466, 'end': 472, 'mesh': 'D020521'}, {'text': 'transient ischaemic attacks', 'type': 'Disease', 'start': 474, 'end': 501, 'mesh': 'D002546'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 503, 'end': 516, 'mesh': 'D001943'}, {'text': 'colorectal cancer', 'type': 'Disease', 'start': 518, 'end': 535, 'mesh': 'D015179'}, {'text': 'ovarian cancer', 'type': 'Disease', 'start': 537, 'end': 551, 'mesh': 'D010051'}, {'text': 'endometrial cancer', 'type': 'Disease', 'start': 553, 'end': 571, 'mesh': 'D016889'}, {'text': 'gallbladder disease', 'type': 'Disease', 'start': 573, 'end': 592, 'mesh': 'D005705'}, {'text': 'dementia', 'type': 'Disease', 'start': 614, 'end': 622, 'mesh': 'D003704'}, {'text': 'fractures', 'type': 'Disease', 'start': 624, 'end': 633, 'mesh': 'D050723'}, {'text': 'oestrogens', 'type': 'Chemical', 'start': 1032, 'end': 1042, 'mesh': 'D004967'}, {'text': 'progestogens', 'type': 'Chemical', 'start': 1059, 'end': 1071, 'mesh': 'D011374'}, {'text': 'venous thromboembolism', 'type': 'Disease', 'start': 1664, 'end': 1686, 'mesh': 'D054556'}, {'text': 'stroke', 'type': 'Disease', 'start': 1729, 'end': 1735, 'mesh': 'D020521'}, {'text': 'breast cancer', 'type': 'Disease', 'start': 1753, 'end': 1766, 'mesh': 'D001943'}, {'text': 'gallbladder disease', 'type': 'Disease', 'start': 1787, 'end': 1806, 'mesh': 'D005705'}, {'text': 'oestrogen', 'type': 'Chemical', 'start': 1818, 'end': 1827, 'mesh': 'D004967'}, {'text': 'stroke', 'type': 'Disease', 'start': 1877, 'end': 1883, 'mesh': 'D020521'}, {'text': 'gallbladder disease', 'type': 'Disease', 'start': 1888, 'end': 1907, 'mesh': 'D005705'}, {'text': 'fractures', 'type': 'Disease', 'start': 1998, 'end': 2007, 'mesh': 'D050723'}, {'text': 'colon cancer', 'type': 'Disease', 'start': 2012, 'end': 2024, 'mesh': 'D003110'}, {'text': 'dementia', 'type': 'Disease', 'start': 2188, 'end': 2196, 'mesh': 'D003704'}, {'text': 'cardiovascular disease', 'type': 'Disease', 'start': 2215, 'end': 2237, 'mesh': 'D002318'}, {'text': 'venous thromboembolism', 'type': 'Disease', 'start': 2315, 'end': 2337, 'mesh': 'D054556'}, {'text': 'oestrogen', 'type': 'Chemical', 'start': 2524, 'end': 2533, 'mesh': 'D004967'}, {'text': 'venous thromboembolism', 'type': 'Disease', 'start': 2635, 'end': 2657, 'mesh': 'D054556'}, {'text': 'chronic disease', 'type': 'Disease', 'start': 2809, 'end': 2824, 'mesh': 'D002908'}]"
+1407,16083708,Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period.,"BACKGROUND & AIMS: Progress in the understanding of susceptibility factors to drug-induced liver injury (DILI) and outcome predictability are hampered by the lack of systematic programs to detect bona fide cases. METHODS: A cooperative network was created in 1994 in Spain to identify all suspicions of DILI following a prospective structured report form. The liver damage was characterized according to hepatocellular, cholestatic, and mixed laboratory criteria and to histologic criteria when available. Further evaluation of causality assessment was centrally performed. RESULTS: Since April 1994 to August 2004, 461 out of 570 submitted cases, involving 505 drugs, were deemed to be related to DILI. The antiinfective group of drugs was the more frequently incriminated, amoxicillin-clavulanate accounting for the 12.8% of the whole series. The hepatocellular pattern of damage was the most common (58%), was inversely correlated with age (P < .0001), and had the worst outcome (Cox regression, P < .034). Indeed, the incidence of liver transplantation and death in this group was 11.7% if patients had jaundice at presentation, whereas the corresponding figure was 3.8% in nonjaundiced patients (P < .04). Factors associated with the development of fulminant hepatic failure were female sex (OR = 25; 95% CI: 4.1-151; P < .0001), hepatocellular damage (OR = 7.9; 95% CI: 1.6-37; P < .009), and higher baseline plasma bilirubin value (OR = 1.15; 95% CI: 1.09-1.22; P < .0001). CONCLUSIONS: Patients with drug-induced hepatocellular jaundice have 11.7% chance of progressing to death or transplantation. Amoxicillin-clavulanate stands out as the most common drug related to DILI.","[{'text': 'Drug-induced liver injury', 'type': 'Disease', 'start': 0, 'end': 25, 'mesh': 'D056486'}, {'text': 'drug-induced liver injury', 'type': 'Disease', 'start': 192, 'end': 217, 'mesh': 'D056486'}, {'text': 'DILI', 'type': 'Disease', 'start': 219, 'end': 223, 'mesh': 'D056486'}, {'text': 'DILI', 'type': 'Disease', 'start': 417, 'end': 421, 'mesh': 'D056486'}, {'text': 'liver damage', 'type': 'Disease', 'start': 474, 'end': 486, 'mesh': 'D056486'}, {'text': 'cholestatic', 'type': 'Disease', 'start': 534, 'end': 545, 'mesh': 'D002779'}, {'text': 'DILI', 'type': 'Disease', 'start': 812, 'end': 816, 'mesh': 'D056486'}, {'text': 'amoxicillin-clavulanate', 'type': 'Chemical', 'start': 889, 'end': 912, 'mesh': 'D019980'}, {'text': 'jaundice', 'type': 'Disease', 'start': 1221, 'end': 1229, 'mesh': 'D007565'}, {'text': 'fulminant hepatic failure', 'type': 'Disease', 'start': 1368, 'end': 1393, 'mesh': 'D017114'}, {'text': 'bilirubin', 'type': 'Chemical', 'start': 1536, 'end': 1545, 'mesh': 'D001663'}, {'text': 'jaundice', 'type': 'Disease', 'start': 1650, 'end': 1658, 'mesh': 'D007565'}, {'text': 'Amoxicillin-clavulanate', 'type': 'Chemical', 'start': 1721, 'end': 1744, 'mesh': 'D019980'}, {'text': 'DILI', 'type': 'Disease', 'start': 1791, 'end': 1795, 'mesh': 'D056486'}]"
+1408,16092435,Morphological evaluation of the effect of d-ribose on adriamycin-evoked cardiotoxicity in rats.,The influence of d-ribose on adriamycin-induced myocardiopathy in rats was studied. Adriamycin in the cumulative dose of 25 mg/kg evoked fully developed cardiac toxicity. D-ribose in the multiple doses of 200 mg/kg did not influence ADR cardiotoxicity.,"[{'text': 'd-ribose', 'type': 'Chemical', 'start': 42, 'end': 50, 'mesh': 'D012266'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 54, 'end': 64, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 72, 'end': 86, 'mesh': 'D066126'}, {'text': 'd-ribose', 'type': 'Chemical', 'start': 113, 'end': 121, 'mesh': 'D012266'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 125, 'end': 135, 'mesh': 'D004317'}, {'text': 'myocardiopathy', 'type': 'Disease', 'start': 144, 'end': 158, 'mesh': 'D009202'}, {'text': 'Adriamycin', 'type': 'Chemical', 'start': 180, 'end': 190, 'mesh': 'D004317'}, {'text': 'cardiac toxicity', 'type': 'Disease', 'start': 249, 'end': 265, 'mesh': 'D066126'}, {'text': 'D-ribose', 'type': 'Chemical', 'start': 267, 'end': 275, 'mesh': 'D012266'}, {'text': 'ADR', 'type': 'Chemical', 'start': 329, 'end': 332, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 333, 'end': 347, 'mesh': 'D066126'}]"
+1409,16112787,In vivo evidences suggesting the role of oxidative stress in pathogenesis of vancomycin-induced nephrotoxicity: protection by erdosteine.,"The aims of this study were to examine vancomycin (VCM)-induced oxidative stress that promotes production of reactive oxygen species (ROS) and to investigate the role of erdosteine, an expectorant agent, which has also antioxidant properties, on kidney tissue against the possible VCM-induced renal impairment in rats. Rats were divided into three groups: sham, VCM and VCM plus erdosteine. VCM was administrated intraperitoneally (i.p.) with 200mgkg(-1) twice daily for 7 days. Erdosteine was administered orally. VCM administration to control rats significantly increased renal malondialdehyde (MDA) and urinary N-acetyl-beta-d-glucosaminidase (NAG, a marker of renal tubular injury) excretion but decreased superoxide dismutase (SOD) and catalase (CAT) activities. Erdosteine administration with VCM injections caused significantly decreased renal MDA and urinary NAG excretion, and increased SOD activity, but not CAT activity in renal tissue when compared with VCM alone. Erdosteine showed histopathological protection against VCM-induced nephrotoxicity. There were a significant dilatation of tubular lumens, extensive epithelial cell vacuolization, atrophy, desquamation, and necrosis in VCM-treated rats more than those of the control and the erdosteine groups. Erdosteine caused a marked reduction in the extent of tubular damage. It is concluded that oxidative tubular damage plays an important role in the VCM-induced nephrotoxicity and the modulation of oxidative stress with erdosteine reduces the VCM-induced kidney damage both at the biochemical and histological levels.","[{'text': 'vancomycin', 'type': 'Chemical', 'start': 77, 'end': 87, 'mesh': 'D014640'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 96, 'end': 110, 'mesh': 'D007674'}, {'text': 'erdosteine', 'type': 'Chemical', 'start': 126, 'end': 136, 'mesh': 'C048498'}, {'text': 'vancomycin', 'type': 'Chemical', 'start': 177, 'end': 187, 'mesh': 'D014640'}, {'text': 'VCM', 'type': 'Chemical', 'start': 189, 'end': 192, 'mesh': 'D014640'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 256, 'end': 262, 'mesh': 'D010100'}, {'text': 'erdosteine', 'type': 'Chemical', 'start': 308, 'end': 318, 'mesh': 'C048498'}, {'text': 'VCM', 'type': 'Chemical', 'start': 419, 'end': 422, 'mesh': 'D014640'}, {'text': 'renal impairment', 'type': 'Disease', 'start': 431, 'end': 447, 'mesh': 'D007674'}, {'text': 'VCM', 'type': 'Chemical', 'start': 500, 'end': 503, 'mesh': 'D014640'}, {'text': 'VCM', 'type': 'Chemical', 'start': 508, 'end': 511, 'mesh': 'D014640'}, {'text': 'erdosteine', 'type': 'Chemical', 'start': 517, 'end': 527, 'mesh': 'C048498'}, {'text': 'VCM', 'type': 'Chemical', 'start': 529, 'end': 532, 'mesh': 'D014640'}, {'text': 'Erdosteine', 'type': 'Chemical', 'start': 617, 'end': 627, 'mesh': 'C048498'}, {'text': 'VCM', 'type': 'Chemical', 'start': 653, 'end': 656, 'mesh': 'D014640'}, {'text': 'malondialdehyde', 'type': 'Chemical', 'start': 718, 'end': 733, 'mesh': 'D008315'}, {'text': 'MDA', 'type': 'Chemical', 'start': 735, 'end': 738, 'mesh': 'D008315'}, {'text': 'renal tubular injury', 'type': 'Disease', 'start': 802, 'end': 822, 'mesh': 'D007674'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 848, 'end': 858, 'mesh': 'D013481'}, {'text': 'Erdosteine', 'type': 'Chemical', 'start': 906, 'end': 916, 'mesh': 'C048498'}, {'text': 'VCM', 'type': 'Chemical', 'start': 937, 'end': 940, 'mesh': 'D014640'}, {'text': 'MDA', 'type': 'Chemical', 'start': 989, 'end': 992, 'mesh': 'D008315'}, {'text': 'VCM', 'type': 'Chemical', 'start': 1104, 'end': 1107, 'mesh': 'D014640'}, {'text': 'Erdosteine', 'type': 'Chemical', 'start': 1115, 'end': 1125, 'mesh': 'C048498'}, {'text': 'VCM', 'type': 'Chemical', 'start': 1170, 'end': 1173, 'mesh': 'D014640'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1182, 'end': 1196, 'mesh': 'D007674'}, {'text': 'atrophy', 'type': 'Disease', 'start': 1294, 'end': 1301, 'mesh': 'D001284'}, {'text': 'desquamation', 'type': 'Disease', 'start': 1303, 'end': 1315, 'mesh': '-1'}, {'text': 'necrosis', 'type': 'Disease', 'start': 1321, 'end': 1329, 'mesh': 'D009336'}, {'text': 'VCM', 'type': 'Chemical', 'start': 1333, 'end': 1336, 'mesh': 'D014640'}, {'text': 'erdosteine', 'type': 'Chemical', 'start': 1389, 'end': 1399, 'mesh': 'C048498'}, {'text': 'Erdosteine', 'type': 'Chemical', 'start': 1408, 'end': 1418, 'mesh': 'C048498'}, {'text': 'VCM', 'type': 'Chemical', 'start': 1555, 'end': 1558, 'mesh': 'D014640'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 1567, 'end': 1581, 'mesh': 'D007674'}, {'text': 'erdosteine', 'type': 'Chemical', 'start': 1626, 'end': 1636, 'mesh': 'C048498'}, {'text': 'VCM', 'type': 'Chemical', 'start': 1649, 'end': 1652, 'mesh': 'D014640'}, {'text': 'kidney damage', 'type': 'Disease', 'start': 1661, 'end': 1674, 'mesh': 'D007674'}]"
+1410,16309808,Does domperidone potentiate mirtazapine-associated restless legs syndrome?,"There is now evidence to suggest a central role for the dopaminergic system in restless legs syndrome (RLS). For example, the symptoms of RLS can be dramatically improved by levodopa and dopamine agonists, whereas central dopamine D2 receptor antagonists can induce or aggravate RLS symptoms. To our knowledge, there is no previous report regarding whether domperidone, a peripheral dopamine D2 receptor antagonist, can also induce or aggravate symptoms of RLS. Mirtazapine, the first noradrenergic and specific serotonergic antidepressant (NaSSA), has been associated with RLS in several recent publications. The authors report here a depressed patient comorbid with postprandial dyspepsia who developed RLS after mirtazapine had been added to his domperidone therapy. Our patient started to have symptoms of RLS only after he had been treated with mirtazapine, and his RLS symptoms resolved completely upon discontinuation of his mirtazapine. Such a temporal relationship between the use of mirtazapine and the symptoms of RLS in our patient did not support a potentiating effect of domperione on mirtazapine-associated RLS. However, physicians should be aware of the possibility that mirtazapine can be associated with RLS in some individuals, especially those receiving concomitant dopamine D2 receptor antagonists.","[{'text': 'domperidone', 'type': 'Chemical', 'start': 5, 'end': 16, 'mesh': 'D004294'}, {'text': 'mirtazapine', 'type': 'Chemical', 'start': 28, 'end': 39, 'mesh': 'C035133'}, {'text': 'restless legs syndrome', 'type': 'Disease', 'start': 51, 'end': 73, 'mesh': 'D012148'}, {'text': 'restless legs syndrome', 'type': 'Disease', 'start': 154, 'end': 176, 'mesh': 'D012148'}, {'text': 'RLS', 'type': 'Disease', 'start': 178, 'end': 181, 'mesh': 'D012148'}, {'text': 'RLS', 'type': 'Disease', 'start': 213, 'end': 216, 'mesh': 'D012148'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 249, 'end': 257, 'mesh': 'D007980'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 262, 'end': 270, 'mesh': 'D004298'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 297, 'end': 305, 'mesh': 'D004298'}, {'text': 'RLS', 'type': 'Disease', 'start': 354, 'end': 357, 'mesh': 'D012148'}, {'text': 'domperidone', 'type': 'Chemical', 'start': 432, 'end': 443, 'mesh': 'D004294'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 458, 'end': 466, 'mesh': 'D004298'}, {'text': 'RLS', 'type': 'Disease', 'start': 532, 'end': 535, 'mesh': 'D012148'}, {'text': 'Mirtazapine', 'type': 'Chemical', 'start': 537, 'end': 548, 'mesh': 'C035133'}, {'text': 'RLS', 'type': 'Disease', 'start': 649, 'end': 652, 'mesh': 'D012148'}, {'text': 'postprandial dyspepsia', 'type': 'Disease', 'start': 743, 'end': 765, 'mesh': 'D004415'}, {'text': 'RLS', 'type': 'Disease', 'start': 780, 'end': 783, 'mesh': 'D012148'}, {'text': 'mirtazapine', 'type': 'Chemical', 'start': 790, 'end': 801, 'mesh': 'C035133'}, {'text': 'domperidone', 'type': 'Chemical', 'start': 824, 'end': 835, 'mesh': 'D004294'}, {'text': 'RLS', 'type': 'Disease', 'start': 885, 'end': 888, 'mesh': 'D012148'}, {'text': 'mirtazapine', 'type': 'Chemical', 'start': 925, 'end': 936, 'mesh': 'C035133'}, {'text': 'RLS', 'type': 'Disease', 'start': 946, 'end': 949, 'mesh': 'D012148'}, {'text': 'mirtazapine', 'type': 'Chemical', 'start': 1007, 'end': 1018, 'mesh': 'C035133'}, {'text': 'mirtazapine', 'type': 'Chemical', 'start': 1068, 'end': 1079, 'mesh': 'C035133'}, {'text': 'RLS', 'type': 'Disease', 'start': 1100, 'end': 1103, 'mesh': 'D012148'}, {'text': 'domperione', 'type': 'Chemical', 'start': 1160, 'end': 1170, 'mesh': 'D004294'}, {'text': 'mirtazapine', 'type': 'Chemical', 'start': 1174, 'end': 1185, 'mesh': 'C035133'}, {'text': 'RLS', 'type': 'Disease', 'start': 1197, 'end': 1200, 'mesh': 'D012148'}, {'text': 'mirtazapine', 'type': 'Chemical', 'start': 1262, 'end': 1273, 'mesh': 'C035133'}, {'text': 'RLS', 'type': 'Disease', 'start': 1297, 'end': 1300, 'mesh': 'D012148'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1361, 'end': 1369, 'mesh': 'D004298'}]"
+1411,16323982,Antiandrogenic therapy can cause coronary arterial disease.,"AIM: To study the change of lipid metabolism by antiandrogen therapy in patients with prostate cancer. MATERIALS AND METHODS: We studied with a 2.5 years follow-up the changes in plasma cholesterols (C), triglycerides (TG), lipoproteins (LP), and apolipoproteins (Apo) B-100, A-I, and A-II pro fi les in 24 patients of mean age 60 years with low risk prostate cancer (stage: T1cN0M0, Gleason score: 2-5) during treatment with cyproterone acetate (CPA) without surgical management or radiation therapy. RESULTS: Significant decreases of HDL-C, Apo A-I and Apo A-II and an increase of triglyceride levels in VLDL were induced by CPA. After a period of 2.5 years on CPA treatment, four patients out of twenty-four were found to be affected by coronary heart disease. CONCLUSIONS: Ischaemic coronary arteriosclerosis with an incidence rate of 16.6% as caused by prolonged CPA therapy is mediated through changes in HDL cholesterol, Apo A-I and Apo A-II pro fi les, other than the well-known hyperglyceridemic effect caused by estrogen.","[{'text': 'coronary arterial disease', 'type': 'Disease', 'start': 33, 'end': 58, 'mesh': 'D003324'}, {'text': 'prostate cancer', 'type': 'Disease', 'start': 146, 'end': 161, 'mesh': 'D011471'}, {'text': 'cholesterols', 'type': 'Chemical', 'start': 246, 'end': 258, 'mesh': 'D002784'}, {'text': 'C', 'type': 'Chemical', 'start': 260, 'end': 261, 'mesh': 'D002784'}, {'text': 'triglycerides', 'type': 'Chemical', 'start': 264, 'end': 277, 'mesh': 'D014280'}, {'text': 'TG', 'type': 'Chemical', 'start': 279, 'end': 281, 'mesh': 'D014280'}, {'text': 'prostate cancer', 'type': 'Disease', 'start': 411, 'end': 426, 'mesh': 'D011471'}, {'text': 'cyproterone acetate', 'type': 'Chemical', 'start': 486, 'end': 505, 'mesh': 'D017373'}, {'text': 'CPA', 'type': 'Chemical', 'start': 507, 'end': 510, 'mesh': 'D017373'}, {'text': 'triglyceride', 'type': 'Chemical', 'start': 643, 'end': 655, 'mesh': 'D014280'}, {'text': 'CPA', 'type': 'Chemical', 'start': 687, 'end': 690, 'mesh': 'D017373'}, {'text': 'CPA', 'type': 'Chemical', 'start': 723, 'end': 726, 'mesh': 'D017373'}, {'text': 'coronary heart disease', 'type': 'Disease', 'start': 800, 'end': 822, 'mesh': 'D003327'}, {'text': 'coronary arteriosclerosis', 'type': 'Disease', 'start': 847, 'end': 872, 'mesh': 'D003324'}, {'text': 'CPA', 'type': 'Chemical', 'start': 928, 'end': 931, 'mesh': 'D017373'}, {'text': 'cholesterol', 'type': 'Chemical', 'start': 975, 'end': 986, 'mesh': 'D002784'}, {'text': 'hyperglyceridemic effect', 'type': 'Disease', 'start': 1047, 'end': 1071, 'mesh': 'D050171'}, {'text': 'estrogen', 'type': 'Chemical', 'start': 1082, 'end': 1090, 'mesh': 'D004967'}]"
+1412,16369751,5-Fluorouracil cardiotoxicity induced by alpha-fluoro-beta-alanine.,"Cardiotoxicity is a rare complication occurring during 5-fluorouracil (5-FU) treatment for malignancies. We herein report the case of a 70-year-old man with 5-FU-induced cardiotoxicity, in whom a high serum level of alpha-fluoro-beta-alanine (FBAL) was observed. The patient, who had unresectable colon cancer metastases to the liver and lung, was referred to us for chemotherapy from an affiliated hospital; he had no cardiac history. After admission, the patient received a continuous intravenous infusion of 5-FU (1000 mg/day), during which precordial pain with right bundle branch block occurred concomitantly with a high serum FBAL concentration of 1955 ng/ml. Both the precordial pain and the electrocardiographic changes disappeared spontaneously after the discontinuation of 5-FU. As the precordial pain in this patient was considered to have been due to 5-FU-induced cardiotoxicity, the administration of 5-FU was abandoned. Instead, oral administration of S-1 (a derivative of 5-FU), at 200 mg/day twice a week, was instituted, because S-1 has a strong inhibitory effect on dihydropyrimidine dehydrogenase, which catalyzes the degradative of 5-FU into FBAL. The serum FBAL concentration subsequently decreased to 352 ng/ml, the same as the value measured on the first day of S-1 administration. Thereafter, no cardiac symptoms were observed. The patient achieved a partial response 6 months after the initiation of the S-1 treatment. The experience of this case, together with a review of the literature, suggests that FBAL is related to 5-FU-induced cardiotoxicity. S-1 may be administered safely to patients with 5-FU-induced cardiotoxicity.","[{'text': '5-Fluorouracil', 'type': 'Chemical', 'start': 0, 'end': 14, 'mesh': 'D005472'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 15, 'end': 29, 'mesh': 'D066126'}, {'text': 'alpha-fluoro-beta-alanine', 'type': 'Chemical', 'start': 41, 'end': 66, 'mesh': 'C032348'}, {'text': 'Cardiotoxicity', 'type': 'Disease', 'start': 68, 'end': 82, 'mesh': 'D066126'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 123, 'end': 137, 'mesh': 'D005472'}, {'text': '5-FU', 'type': 'Chemical', 'start': 139, 'end': 143, 'mesh': 'D005472'}, {'text': 'malignancies', 'type': 'Disease', 'start': 159, 'end': 171, 'mesh': 'D009369'}, {'text': '5-FU', 'type': 'Chemical', 'start': 225, 'end': 229, 'mesh': 'D005472'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 238, 'end': 252, 'mesh': 'D066126'}, {'text': 'alpha-fluoro-beta-alanine', 'type': 'Chemical', 'start': 284, 'end': 309, 'mesh': 'C032348'}, {'text': 'FBAL', 'type': 'Chemical', 'start': 311, 'end': 315, 'mesh': 'C032348'}, {'text': 'colon cancer', 'type': 'Disease', 'start': 365, 'end': 377, 'mesh': 'D003110'}, {'text': '5-FU', 'type': 'Chemical', 'start': 579, 'end': 583, 'mesh': 'D005472'}, {'text': 'precordial pain', 'type': 'Disease', 'start': 612, 'end': 627, 'mesh': 'D002637'}, {'text': 'right bundle branch block', 'type': 'Disease', 'start': 633, 'end': 658, 'mesh': 'D002037'}, {'text': 'FBAL', 'type': 'Chemical', 'start': 700, 'end': 704, 'mesh': 'C032348'}, {'text': 'precordial pain', 'type': 'Disease', 'start': 743, 'end': 758, 'mesh': 'D002637'}, {'text': '5-FU', 'type': 'Chemical', 'start': 851, 'end': 855, 'mesh': 'D005472'}, {'text': 'precordial pain', 'type': 'Disease', 'start': 864, 'end': 879, 'mesh': 'D002637'}, {'text': '5-FU', 'type': 'Chemical', 'start': 931, 'end': 935, 'mesh': 'D005472'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 944, 'end': 958, 'mesh': 'D066126'}, {'text': '5-FU', 'type': 'Chemical', 'start': 982, 'end': 986, 'mesh': 'D005472'}, {'text': '5-FU', 'type': 'Chemical', 'start': 1055, 'end': 1059, 'mesh': 'D005472'}, {'text': 'dihydropyrimidine', 'type': 'Chemical', 'start': 1152, 'end': 1169, 'mesh': 'C020047'}, {'text': '5-FU', 'type': 'Chemical', 'start': 1220, 'end': 1224, 'mesh': 'D005472'}, {'text': 'FBAL', 'type': 'Chemical', 'start': 1230, 'end': 1234, 'mesh': 'C032348'}, {'text': 'FBAL', 'type': 'Chemical', 'start': 1246, 'end': 1250, 'mesh': 'C032348'}, {'text': 'cardiac symptoms', 'type': 'Disease', 'start': 1388, 'end': 1404, 'mesh': 'D009461'}, {'text': 'FBAL', 'type': 'Chemical', 'start': 1597, 'end': 1601, 'mesh': 'C032348'}, {'text': '5-FU', 'type': 'Chemical', 'start': 1616, 'end': 1620, 'mesh': 'D005472'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1629, 'end': 1643, 'mesh': 'D066126'}, {'text': '5-FU', 'type': 'Chemical', 'start': 1693, 'end': 1697, 'mesh': 'D005472'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 1706, 'end': 1720, 'mesh': 'D066126'}]"
+1413,16565833,The influence of the time interval between monoHER and doxorubicin administration on the protection against doxorubicin-induced cardiotoxicity in mice.,"PURPOSE: Despite its well-known cardiotoxicity, the anthracyclin doxorubicin (DOX) continues to be an effective and widely used chemotherapeutic agent. DOX-induced cardiac damage presumably results from the formation of free radicals by DOX. Reactive oxygen species particularly affect the cardiac myocytes because these cells seem to have a relatively poor antioxidant defense system. The semisynthetic flavonoid monohydroxyethylrutoside (monoHER) showed cardioprotection against DOX-induced cardiotoxicity through its radical scavenging and iron chelating properties. Because of the relatively short final half-life of monoHER (about 30 min), it is expected that the time interval between monoHER and DOX might be of influence on the cardioprotective effect of monoHER. Therefore, the aim of the present study was to investigate this possible effect. METHODS: Six groups of 6 BALB/c mice were treated with saline, DOX alone or DOX (4 mg/kg i.v.) preceded by monoHER (500 mg/kg i.p.) with an interval of 10, 30, 60 or 120 min. After a 6-week treatment period and additional observation for 2 weeks, the mice were sacrificed. Their cardiac tissues were processed for light microscopy, after which cardiomyocyte damage was evaluated according to Billingham (in Cancer Treat Rep 62(6):865-872, 1978). Microscopic evaluation revealed that treatment with DOX alone induced significant cardiac damage in comparison to the saline control group (P<0.001). RESULTS: The number of damaged cardiomyocytes was 9.6-fold (95% CI 4.4-21.0) higher in mice treated with DOX alone than that in animals of the control group. The ratio of aberrant cardiomyocytes in mice treated with DOX preceded by monoHER and those in mice treated with saline ranged from 1.6 to 2.8 (mean 2.2, 95% CI 1.2-4.1, P=0.019). The mean protective effect by adding monoHER before DOX led to a significant 4.4-fold reduction (P<0.001, 95% CI 2.3-8.2) of abnormal cardiomyocytes. This protective effect did not depend on the time interval between monoHER and DOX administration (P=0.345). CONCLUSION: The results indicate that in an outpatient clinical setting monoHER may be administered shortly before DOX.","[{'text': 'monoHER', 'type': 'Chemical', 'start': 43, 'end': 50, 'mesh': 'C522803'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 55, 'end': 66, 'mesh': 'D004317'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 108, 'end': 119, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 128, 'end': 142, 'mesh': 'D066126'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 184, 'end': 198, 'mesh': 'D066126'}, {'text': 'doxorubicin', 'type': 'Chemical', 'start': 217, 'end': 228, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 230, 'end': 233, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 304, 'end': 307, 'mesh': 'D004317'}, {'text': 'cardiac damage', 'type': 'Disease', 'start': 316, 'end': 330, 'mesh': 'D006331'}, {'text': 'DOX', 'type': 'Chemical', 'start': 389, 'end': 392, 'mesh': 'D004317'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 403, 'end': 409, 'mesh': 'D010100'}, {'text': 'flavonoid', 'type': 'Chemical', 'start': 556, 'end': 565, 'mesh': 'D005419'}, {'text': 'monohydroxyethylrutoside', 'type': 'Chemical', 'start': 566, 'end': 590, 'mesh': 'C522803'}, {'text': 'monoHER', 'type': 'Chemical', 'start': 592, 'end': 599, 'mesh': 'C522803'}, {'text': 'DOX', 'type': 'Chemical', 'start': 633, 'end': 636, 'mesh': 'D004317'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 645, 'end': 659, 'mesh': 'D066126'}, {'text': 'iron', 'type': 'Chemical', 'start': 695, 'end': 699, 'mesh': 'D007501'}, {'text': 'monoHER', 'type': 'Chemical', 'start': 773, 'end': 780, 'mesh': 'C522803'}, {'text': 'monoHER', 'type': 'Chemical', 'start': 843, 'end': 850, 'mesh': 'C522803'}, {'text': 'DOX', 'type': 'Chemical', 'start': 855, 'end': 858, 'mesh': 'D004317'}, {'text': 'monoHER', 'type': 'Chemical', 'start': 915, 'end': 922, 'mesh': 'C522803'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1068, 'end': 1071, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1081, 'end': 1084, 'mesh': 'D004317'}, {'text': 'monoHER', 'type': 'Chemical', 'start': 1112, 'end': 1119, 'mesh': 'C522803'}, {'text': 'cardiomyocyte damage', 'type': 'Disease', 'start': 1349, 'end': 1369, 'mesh': 'D009202'}, {'text': 'Cancer', 'type': 'Disease', 'start': 1412, 'end': 1418, 'mesh': 'D009369'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1503, 'end': 1506, 'mesh': 'D004317'}, {'text': 'cardiac damage', 'type': 'Disease', 'start': 1533, 'end': 1547, 'mesh': 'D006331'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1706, 'end': 1709, 'mesh': 'D004317'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1817, 'end': 1820, 'mesh': 'D004317'}, {'text': 'monoHER', 'type': 'Chemical', 'start': 1833, 'end': 1840, 'mesh': 'C522803'}, {'text': 'monoHER', 'type': 'Chemical', 'start': 1976, 'end': 1983, 'mesh': 'C522803'}, {'text': 'DOX', 'type': 'Chemical', 'start': 1991, 'end': 1994, 'mesh': 'D004317'}, {'text': 'monoHER', 'type': 'Chemical', 'start': 2156, 'end': 2163, 'mesh': 'C522803'}, {'text': 'DOX', 'type': 'Chemical', 'start': 2168, 'end': 2171, 'mesh': 'D004317'}, {'text': 'monoHER', 'type': 'Chemical', 'start': 2270, 'end': 2277, 'mesh': 'C522803'}, {'text': 'DOX', 'type': 'Chemical', 'start': 2313, 'end': 2316, 'mesh': 'D004317'}]"
+1414,16723784,Clinical evaluation of adverse effects during bepridil administration for atrial fibrillation and flutter.,"BACKGROUND: Bepridil hydrochloride (Bpd) has attracted attention as an effective drug for atrial fibrillation (AF) and atrial flutter (AFL). However, serious adverse effects, including torsade de pointes (Tdp), have been reported. METHODS AND RESULTS: Adverse effects of Bpd requiring discontinuation of treatment were evaluated. Bpd was administered to 459 patients (361 males, 63+/-12 years old) comprising 378 AF and 81 AFL cases. Mean left ventricular ejection fraction and atrial dimension (LAD) were 66+/-11% and 40+/-6 mm, respectively. Adverse effects were observed in 19 patients (4%) during an average follow-up of 20 months. There was marked QT prolongation greater than 0.55 s in 13 patients, bradycardia less than 40 beats/min in 6 patients, dizziness and general fatigue in 1 patient each. In 4 of 13 patients with QT prolongation, Tdp occurred. The major triggering factors of Tdp were hypokalemia and sudden decrease in heart rate. There were no differences in the clinical backgrounds of the patients with and without Tdp other than LAD and age, which were larger and older in the patients with Tdp. CONCLUSION: Careful observation of serum potassium concentration and the ECG should always be done during Bpd administration, particularly in elderly patients.","[{'text': 'bepridil', 'type': 'Chemical', 'start': 46, 'end': 54, 'mesh': 'D015764'}, {'text': 'Bepridil hydrochloride', 'type': 'Chemical', 'start': 119, 'end': 141, 'mesh': 'D015764'}, {'text': 'Bpd', 'type': 'Chemical', 'start': 143, 'end': 146, 'mesh': 'D015764'}, {'text': 'atrial fibrillation', 'type': 'Disease', 'start': 197, 'end': 216, 'mesh': 'D001281'}, {'text': 'AF', 'type': 'Disease', 'start': 218, 'end': 220, 'mesh': 'D001281'}, {'text': 'atrial flutter', 'type': 'Disease', 'start': 226, 'end': 240, 'mesh': 'D001282'}, {'text': 'AFL', 'type': 'Disease', 'start': 242, 'end': 245, 'mesh': 'D001282'}, {'text': 'torsade de pointes', 'type': 'Disease', 'start': 292, 'end': 310, 'mesh': 'D016171'}, {'text': 'Tdp', 'type': 'Disease', 'start': 312, 'end': 315, 'mesh': 'D016171'}, {'text': 'Bpd', 'type': 'Chemical', 'start': 378, 'end': 381, 'mesh': 'D015764'}, {'text': 'Bpd', 'type': 'Chemical', 'start': 437, 'end': 440, 'mesh': 'D015764'}, {'text': 'AF', 'type': 'Disease', 'start': 520, 'end': 522, 'mesh': 'D001281'}, {'text': 'AFL', 'type': 'Disease', 'start': 530, 'end': 533, 'mesh': 'D001282'}, {'text': 'QT prolongation', 'type': 'Disease', 'start': 760, 'end': 775, 'mesh': 'D008133'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 812, 'end': 823, 'mesh': 'D001919'}, {'text': 'dizziness', 'type': 'Disease', 'start': 862, 'end': 871, 'mesh': 'D004244'}, {'text': 'fatigue', 'type': 'Disease', 'start': 884, 'end': 891, 'mesh': 'D005221'}, {'text': 'QT prolongation', 'type': 'Disease', 'start': 936, 'end': 951, 'mesh': 'D008133'}, {'text': 'Tdp', 'type': 'Disease', 'start': 953, 'end': 956, 'mesh': 'D016171'}, {'text': 'Tdp', 'type': 'Disease', 'start': 999, 'end': 1002, 'mesh': 'D016171'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 1008, 'end': 1019, 'mesh': 'D007008'}, {'text': 'Tdp', 'type': 'Disease', 'start': 1142, 'end': 1145, 'mesh': 'D016171'}, {'text': 'Tdp', 'type': 'Disease', 'start': 1219, 'end': 1222, 'mesh': 'D016171'}, {'text': 'potassium', 'type': 'Chemical', 'start': 1265, 'end': 1274, 'mesh': 'D011188'}, {'text': 'Bpd', 'type': 'Chemical', 'start': 1330, 'end': 1333, 'mesh': 'D015764'}]"
+1415,16731636,Enhanced isoproterenol-induced cardiac hypertrophy in transgenic rats with low brain angiotensinogen.,"We have previously shown that a permanent deficiency in the brain renin-angiotensin system (RAS) may increase the sensitivity of the baroreflex control of heart rate. In this study we aimed at studying the involvement of the brain RAS in the cardiac reactivity to the beta-adrenoceptor (beta-AR) agonist isoproterenol (Iso). Transgenic rats with low brain angiotensinogen (TGR) were used. In isolated hearts, Iso induced a significantly greater increase in left ventricular (LV) pressure and maximal contraction (+dP/dt(max)) in the TGR than in the Sprague-Dawley (SD) rats. LV hypertrophy induced by Iso treatment was significantly higher in TGR than in SD rats (in g LV wt/100 g body wt, 0.28 +/- 0.004 vs. 0.24 +/- 0.004, respectively). The greater LV hypertrophy in TGR rats was associated with more pronounced downregulation of beta-AR and upregulation of LV beta-AR kinase-1 mRNA levels compared with those in SD rats. The decrease in the heart rate (HR) induced by the beta-AR antagonist metoprolol in conscious rats was significantly attenuated in TGR compared with SD rats (-9.9 +/- 1.7% vs. -18.1 +/- 1.5%), whereas the effect of parasympathetic blockade by atropine on HR was similar in both strains. These results indicate that TGR are more sensitive to beta-AR agonist-induced cardiac inotropic response and hypertrophy, possibly due to chronically low sympathetic outflow directed to the heart.","[{'text': 'isoproterenol', 'type': 'Chemical', 'start': 9, 'end': 22, 'mesh': 'D007545'}, {'text': 'cardiac hypertrophy', 'type': 'Disease', 'start': 31, 'end': 50, 'mesh': 'D006332'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 174, 'end': 185, 'mesh': 'D000804'}, {'text': 'isoproterenol', 'type': 'Chemical', 'start': 406, 'end': 419, 'mesh': 'D007545'}, {'text': 'Iso', 'type': 'Chemical', 'start': 421, 'end': 424, 'mesh': 'D007545'}, {'text': 'Iso', 'type': 'Chemical', 'start': 511, 'end': 514, 'mesh': 'D007545'}, {'text': 'LV hypertrophy', 'type': 'Disease', 'start': 677, 'end': 691, 'mesh': 'D006332'}, {'text': 'Iso', 'type': 'Chemical', 'start': 703, 'end': 706, 'mesh': 'D007545'}, {'text': 'LV hypertrophy', 'type': 'Disease', 'start': 854, 'end': 868, 'mesh': 'D006332'}, {'text': 'metoprolol', 'type': 'Chemical', 'start': 1097, 'end': 1107, 'mesh': 'D008790'}, {'text': 'atropine', 'type': 'Chemical', 'start': 1270, 'end': 1278, 'mesh': 'D001285'}, {'text': 'cardiac inotropic', 'type': 'Disease', 'start': 1392, 'end': 1409, 'mesh': 'D006331'}, {'text': 'hypertrophy', 'type': 'Disease', 'start': 1423, 'end': 1434, 'mesh': 'D006984'}]"
+1416,16801510,Drug-induced long QT syndrome in injection drug users receiving methadone: high frequency in hospitalized patients and risk factors.,"BACKGROUND: Drug-induced long QT syndrome is a serious adverse drug reaction. Methadone prolongs the QT interval in vitro in a dose-dependent manner. In the inpatient setting, the frequency of QT interval prolongation with methadone treatment, its dose dependence, and the importance of cofactors such as drug-drug interactions remain unknown. METHODS: We performed a systematic, retrospective study comparing active or former intravenous drug users receiving methadone and those not receiving methadone among all patients hospitalized over a 5-year period in a tertiary care hospital. A total of 167 patients receiving methadone fulfilled the inclusion criteria and were compared with a control group of 80 injection drug users not receiving methadone. In addition to methadone dose, 15 demographic, biological, and pharmacological variables were considered as potential risk factors for QT prolongation. RESULTS: Among 167 methadone maintenance patients, the prevalence of QTc prolongation to 0.50 second((1/2)) or longer was 16.2% compared with 0% in 80 control subjects. Six patients (3.6%) in the methadone group presented torsades de pointes. QTc length was weakly but significantly associated with methadone daily dose (Spearman rank correlation coefficient, 0.20; P<.01). Multivariate regression analysis allowed attribution of 31.8% of QTc variability to methadone dose, cytochrome P-450 3A4 drug-drug interactions, hypokalemia, and altered liver function. CONCLUSIONS: QT interval prolongation in methadone maintenance patients hospitalized in a tertiary care center is a frequent finding. Methadone dose, presence of cytochrome P-450 3A4 inhibitors, potassium level, and liver function contribute to QT prolongation. Long QT syndrome can occur with low doses of methadone.","[{'text': 'long QT syndrome', 'type': 'Disease', 'start': 13, 'end': 29, 'mesh': 'D008133'}, {'text': 'methadone', 'type': 'Chemical', 'start': 64, 'end': 73, 'mesh': 'D008691'}, {'text': 'long QT syndrome', 'type': 'Disease', 'start': 158, 'end': 174, 'mesh': 'D008133'}, {'text': 'Methadone', 'type': 'Chemical', 'start': 211, 'end': 220, 'mesh': 'D008691'}, {'text': 'QT interval prolongation', 'type': 'Disease', 'start': 326, 'end': 350, 'mesh': 'D008133'}, {'text': 'methadone', 'type': 'Chemical', 'start': 356, 'end': 365, 'mesh': 'D008691'}, {'text': 'methadone', 'type': 'Chemical', 'start': 593, 'end': 602, 'mesh': 'D008691'}, {'text': 'methadone', 'type': 'Chemical', 'start': 627, 'end': 636, 'mesh': 'D008691'}, {'text': 'methadone', 'type': 'Chemical', 'start': 753, 'end': 762, 'mesh': 'D008691'}, {'text': 'methadone', 'type': 'Chemical', 'start': 876, 'end': 885, 'mesh': 'D008691'}, {'text': 'methadone', 'type': 'Chemical', 'start': 902, 'end': 911, 'mesh': 'D008691'}, {'text': 'QT prolongation', 'type': 'Disease', 'start': 1022, 'end': 1037, 'mesh': 'D008133'}, {'text': 'methadone', 'type': 'Chemical', 'start': 1058, 'end': 1067, 'mesh': 'D008691'}, {'text': 'methadone', 'type': 'Chemical', 'start': 1235, 'end': 1244, 'mesh': 'D008691'}, {'text': 'torsades de pointes', 'type': 'Disease', 'start': 1261, 'end': 1280, 'mesh': 'D016171'}, {'text': 'methadone', 'type': 'Chemical', 'start': 1338, 'end': 1347, 'mesh': 'D008691'}, {'text': 'methadone', 'type': 'Chemical', 'start': 1497, 'end': 1506, 'mesh': 'D008691'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 1558, 'end': 1569, 'mesh': 'D007008'}, {'text': 'QT interval prolongation', 'type': 'Disease', 'start': 1612, 'end': 1636, 'mesh': 'D008133'}, {'text': 'methadone', 'type': 'Chemical', 'start': 1640, 'end': 1649, 'mesh': 'D008691'}, {'text': 'Methadone', 'type': 'Chemical', 'start': 1733, 'end': 1742, 'mesh': 'D008691'}, {'text': 'potassium', 'type': 'Chemical', 'start': 1794, 'end': 1803, 'mesh': 'D011188'}, {'text': 'QT prolongation', 'type': 'Disease', 'start': 1844, 'end': 1859, 'mesh': 'D008133'}, {'text': 'Long QT syndrome', 'type': 'Disease', 'start': 1861, 'end': 1877, 'mesh': 'D008133'}, {'text': 'methadone', 'type': 'Chemical', 'start': 1906, 'end': 1915, 'mesh': 'D008691'}]"
+1417,16810074,Mechanisms of hypertension induced by nitric oxide (NO) deficiency: focus on venous function.,"Loss of endothelial cell-derived nitric oxide (NO) in hypertension is a hallmark of arterial dysfunction. Experimental hypertension created by the removal of NO, however, involves mechanisms in addition to decreased arterial vasodilator activity. These include augmented endothelin-1 (ET-1) release, increased sympathetic nervous system activity, and elevated tissue oxidative stress. We hypothesized that increased venous smooth muscle (venomotor) tone plays a role in Nomega-nitro-L-arginine (LNNA) hypertension through these mechanisms. Rats were treated with the NO synthase inhibitor LNNA (0.5 g/L in drinking water) for 2 weeks. Mean arterial pressure of conscious rats was 119 +/- 2 mm Hg in control and 194 +/- 5 mm Hg in LNNA rats (P<0.05). Carotid arteries and vena cava were removed for measurement of isometric contraction. Maximal contraction to norepinephrine was modestly reduced in arteries from LNNA compared with control rats whereas the maximum contraction to ET-1 was significantly reduced (54% control). Maximum contraction of vena cava to norepinephrine (37% control) also was reduced but no change in response to ET-1 was observed. Mean circulatory filling pressure, an in vivo measure of venomotor tone, was not elevated in LNNA hypertension at 1 or 2 weeks after LNNA. The superoxide scavenger tempol (30, 100, and 300 micromol kg(-1), IV) did not change arterial pressure in control rats but caused a dose-dependent decrease in LNNA rats (-18 +/- 8, -26 +/- 15, and -54 +/- 11 mm Hg). Similarly, ganglionic blockade with hexamethonium caused a significantly greater fall in LNNA hypertensive rats (76 +/- 9 mm Hg) compared with control rats (35 +/- 10 mm Hg). Carotid arteries, vena cava, and sympathetic ganglia from LNNA rats had higher basal levels of superoxide compared with those from control rats. These data suggest that while NO deficiency increases oxidative stress and sympathetic activity in both arterial and venous vessels, the impact on veins does not make a major contribution to this form of hypertension.","[{'text': 'hypertension', 'type': 'Disease', 'start': 14, 'end': 26, 'mesh': 'D006973'}, {'text': 'nitric oxide', 'type': 'Chemical', 'start': 38, 'end': 50, 'mesh': 'D009569'}, {'text': 'NO', 'type': 'Chemical', 'start': 52, 'end': 54, 'mesh': 'D009569'}, {'text': 'nitric oxide', 'type': 'Chemical', 'start': 127, 'end': 139, 'mesh': 'D009569'}, {'text': 'NO', 'type': 'Chemical', 'start': 141, 'end': 143, 'mesh': 'D009569'}, {'text': 'hypertension', 'type': 'Disease', 'start': 148, 'end': 160, 'mesh': 'D006973'}, {'text': 'arterial dysfunction', 'type': 'Disease', 'start': 178, 'end': 198, 'mesh': 'D018754'}, {'text': 'hypertension', 'type': 'Disease', 'start': 213, 'end': 225, 'mesh': 'D006973'}, {'text': 'NO', 'type': 'Chemical', 'start': 252, 'end': 254, 'mesh': 'D009569'}, {'text': 'Nomega-nitro-L-arginine', 'type': 'Chemical', 'start': 564, 'end': 587, 'mesh': 'D019335'}, {'text': 'LNNA', 'type': 'Chemical', 'start': 589, 'end': 593, 'mesh': 'D019335'}, {'text': 'hypertension', 'type': 'Disease', 'start': 595, 'end': 607, 'mesh': 'D006973'}, {'text': 'NO', 'type': 'Chemical', 'start': 661, 'end': 663, 'mesh': 'D009569'}, {'text': 'LNNA', 'type': 'Chemical', 'start': 683, 'end': 687, 'mesh': 'D019335'}, {'text': 'LNNA', 'type': 'Chemical', 'start': 824, 'end': 828, 'mesh': 'D019335'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 953, 'end': 967, 'mesh': 'D009638'}, {'text': 'LNNA', 'type': 'Chemical', 'start': 1006, 'end': 1010, 'mesh': 'D019335'}, {'text': 'norepinephrine', 'type': 'Chemical', 'start': 1155, 'end': 1169, 'mesh': 'D009638'}, {'text': 'LNNA', 'type': 'Chemical', 'start': 1342, 'end': 1346, 'mesh': 'D019335'}, {'text': 'hypertension', 'type': 'Disease', 'start': 1347, 'end': 1359, 'mesh': 'D006973'}, {'text': 'LNNA', 'type': 'Chemical', 'start': 1382, 'end': 1386, 'mesh': 'D019335'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 1392, 'end': 1402, 'mesh': 'D013481'}, {'text': 'tempol', 'type': 'Chemical', 'start': 1413, 'end': 1419, 'mesh': 'C001803'}, {'text': 'LNNA', 'type': 'Chemical', 'start': 1548, 'end': 1552, 'mesh': 'D019335'}, {'text': 'hexamethonium', 'type': 'Chemical', 'start': 1641, 'end': 1654, 'mesh': 'D018738'}, {'text': 'LNNA', 'type': 'Chemical', 'start': 1694, 'end': 1698, 'mesh': 'D019335'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 1699, 'end': 1711, 'mesh': 'D006973'}, {'text': 'LNNA', 'type': 'Chemical', 'start': 1838, 'end': 1842, 'mesh': 'D019335'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 1875, 'end': 1885, 'mesh': 'D013481'}, {'text': 'NO', 'type': 'Chemical', 'start': 1955, 'end': 1957, 'mesh': 'D009569'}, {'text': 'hypertension', 'type': 'Disease', 'start': 2129, 'end': 2141, 'mesh': 'D006973'}]"
+1418,16867246,Association of DRD2 polymorphisms and chlorpromazine-induced extrapyramidal syndrome in Chinese schizophrenic patients.,"AIM: Extrapyramidal syndrome (EPS) is most commonly affected by typical antipsychotic drugs that have a high affinity with the D2 receptor. Recently, many research groups have reported on the positive relationship between the genetic variations in the DRD2 gene and the therapeutic response in schizophrenia patients as a result of the role of variations in the receptor in modulating receptor expression. In this study, we evaluate the role DRD2 plays in chlorpromazine-induced EPS in schizophrenic patients. METHODS: We identified seven SNP(single nucleotide polymorphism) (-141Cins>del, TaqIB, TaqID, Ser311Cys, rs6275, rs6277 and TaqIA) in the DRD2 gene in 146 schizophrenic inpatients (59 with EPS and 87 without EPS according to the Simpson-Angus Scale) treated with chlorpromazine after 8 weeks. The alleles of all loci were determined by PCR (polymerase chain reaction). RESULTS: Polymorphisms TaqID, Ser311Cys and rs6277 were not polymorphic in the population recruited in the present study. No statistical significance was found in the allele distribution of -141Cins>del, TaqIB, rs6275 and TaqIA or in the estimated haplotypes (constituted by TaqIB, rs6275 and TaqIA) in linkage disequilibrium between the two groups. CONCLUSION: Our results did not lend strong support to the view that the genetic variation of the DRD2 gene plays a major role in the individually variable adverse effect induced by chlorpromazine, at least in Chinese patients with schizophrenia. Our results confirmed a previous study on the relationship between DRD2 and EPS in Caucasians.","[{'text': 'chlorpromazine', 'type': 'Chemical', 'start': 38, 'end': 52, 'mesh': 'D002746'}, {'text': 'extrapyramidal syndrome', 'type': 'Disease', 'start': 61, 'end': 84, 'mesh': 'D001480'}, {'text': 'schizophrenic', 'type': 'Disease', 'start': 96, 'end': 109, 'mesh': 'D012559'}, {'text': 'Extrapyramidal syndrome', 'type': 'Disease', 'start': 125, 'end': 148, 'mesh': 'D001480'}, {'text': 'EPS', 'type': 'Disease', 'start': 150, 'end': 153, 'mesh': 'D001480'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 414, 'end': 427, 'mesh': 'D012559'}, {'text': 'chlorpromazine', 'type': 'Chemical', 'start': 576, 'end': 590, 'mesh': 'D002746'}, {'text': 'EPS', 'type': 'Disease', 'start': 599, 'end': 602, 'mesh': 'D001480'}, {'text': 'schizophrenic', 'type': 'Disease', 'start': 606, 'end': 619, 'mesh': 'D012559'}, {'text': 'schizophrenic', 'type': 'Disease', 'start': 785, 'end': 798, 'mesh': 'D012559'}, {'text': 'EPS', 'type': 'Disease', 'start': 819, 'end': 822, 'mesh': 'D001480'}, {'text': 'EPS', 'type': 'Disease', 'start': 838, 'end': 841, 'mesh': 'D001480'}, {'text': 'chlorpromazine', 'type': 'Chemical', 'start': 893, 'end': 907, 'mesh': 'D002746'}, {'text': 'chlorpromazine', 'type': 'Chemical', 'start': 1531, 'end': 1545, 'mesh': 'D002746'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 1581, 'end': 1594, 'mesh': 'D012559'}, {'text': 'EPS', 'type': 'Disease', 'start': 1672, 'end': 1675, 'mesh': 'D001480'}]"
+1419,16876986,Physical training decreases susceptibility to subsequent pilocarpine-induced seizures in the rat.,"Regular motor activity has many benefits for mental and physical condition but its implications for epilepsy are still controversial. In order to elucidate this problem, we have studied the effect of long-term physical activity on susceptibility to subsequent seizures. Male Wistar rats were subjected to repeated training sessions in a treadmill and swimming pool. Thereafter, seizures were induced by pilocarpine injections in trained and non-trained control groups. During the acute period of status epilepticus, we measured: (1) the latency of the first motor sign, (2) the intensity of seizures, (3) the time when it occurred within the 6-h observation period, and (4) the time when the acute period ended. All these behavioral parameters showed statistically significant changes suggesting that regular physical exercises decrease susceptibility to subsequently induced seizures and ameliorate the course of experimentally induced status epilepticus.","[{'text': 'pilocarpine', 'type': 'Chemical', 'start': 57, 'end': 68, 'mesh': 'D010862'}, {'text': 'seizures', 'type': 'Disease', 'start': 77, 'end': 85, 'mesh': 'D012640'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 198, 'end': 206, 'mesh': 'D004827'}, {'text': 'seizures', 'type': 'Disease', 'start': 358, 'end': 366, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 476, 'end': 484, 'mesh': 'D012640'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 501, 'end': 512, 'mesh': 'D010862'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 594, 'end': 612, 'mesh': 'D013226'}, {'text': 'seizures', 'type': 'Disease', 'start': 689, 'end': 697, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 974, 'end': 982, 'mesh': 'D012640'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 1035, 'end': 1053, 'mesh': 'D013226'}]"
+1420,16880771,Tonic dopaminergic stimulation impairs associative learning in healthy subjects.,"Endogenous dopamine plays a central role in salience coding during associative learning. Administration of the dopamine precursor levodopa enhances learning in healthy subjects and stroke patients. Because levodopa increases both phasic and tonic dopaminergic neurotransmission, the critical mechanism mediating the enhancement of learning is unresolved. We here probed how selective tonic dopaminergic stimulation affects associative learning. Forty healthy subjects were trained in a novel vocabulary of 45 concrete nouns over the course of 5 consecutive training days in a prospective, randomized, double-blind, placebo-controlled design. Subjects received the tonically stimulating dopamine-receptor agonist pergolide (0.1 mg) vs placebo 120 min before training on each training day. The dopamine agonist significantly impaired novel word learning compared to placebo. This learning decrement persisted up to the last follow-up 4 weeks post-training. Subjects treated with pergolide also showed restricted emotional responses compared to the PLACEBO group. The extent of 'flattened' affect with pergolide was related to the degree of learning inhibition. These findings suggest that tonic occupation of dopamine receptors impairs learning by competition with phasic dopamine signals. Thus, phasic signaling seems to be the critical mechanism by which dopamine enhances associative learning in healthy subjects and stroke patients.","[{'text': 'impairs associative learning', 'type': 'Disease', 'start': 31, 'end': 59, 'mesh': 'D007859'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 92, 'end': 100, 'mesh': 'D004298'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 192, 'end': 200, 'mesh': 'D004298'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 211, 'end': 219, 'mesh': 'D007980'}, {'text': 'stroke', 'type': 'Disease', 'start': 262, 'end': 268, 'mesh': 'D020521'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 287, 'end': 295, 'mesh': 'D007980'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 767, 'end': 775, 'mesh': 'D004298'}, {'text': 'pergolide', 'type': 'Chemical', 'start': 793, 'end': 802, 'mesh': 'D010479'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 873, 'end': 881, 'mesh': 'D004298'}, {'text': 'impaired novel word learning', 'type': 'Disease', 'start': 904, 'end': 932, 'mesh': 'D007859'}, {'text': 'pergolide', 'type': 'Chemical', 'start': 1058, 'end': 1067, 'mesh': 'D010479'}, {'text': 'pergolide', 'type': 'Chemical', 'start': 1180, 'end': 1189, 'mesh': 'D010479'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1288, 'end': 1296, 'mesh': 'D004298'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1351, 'end': 1359, 'mesh': 'D004298'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 1436, 'end': 1444, 'mesh': 'D004298'}, {'text': 'stroke', 'type': 'Disease', 'start': 1499, 'end': 1505, 'mesh': 'D020521'}]"
+1421,16906379,Minocycline-induced vasculitis fulfilling the criteria of polyarteritis nodosa.,"A 47-year-old man who had been taking minocycline for palmoplantar pustulosis developed fever, myalgias, polyneuropathy, and testicular pain, with elevated C-reactive protein (CRP). Neither myeloperoxidase- nor proteinase-3-antineutrophil cytoplasmic antibody was positive. These manifestations met the American College of Rheumatology 1990 criteria for the classification of polyarteritis nodosa. Stopping minocycline led to amelioration of symptoms and normalization of CRP level. To our knowledge, this is the second case of minocycline-induced vasculitis satisfying the criteria. Differential diagnosis for drug-induced disease is invaluable even for patients with classical polyarteritis nodosa.","[{'text': 'Minocycline', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D008911'}, {'text': 'vasculitis', 'type': 'Disease', 'start': 20, 'end': 30, 'mesh': 'D014657'}, {'text': 'polyarteritis nodosa', 'type': 'Disease', 'start': 58, 'end': 78, 'mesh': 'D010488'}, {'text': 'minocycline', 'type': 'Chemical', 'start': 118, 'end': 129, 'mesh': 'D008911'}, {'text': 'palmoplantar pustulosis', 'type': 'Disease', 'start': 134, 'end': 157, 'mesh': 'D011565'}, {'text': 'fever', 'type': 'Disease', 'start': 168, 'end': 173, 'mesh': 'D005334'}, {'text': 'myalgias', 'type': 'Disease', 'start': 175, 'end': 183, 'mesh': 'D063806'}, {'text': 'polyneuropathy', 'type': 'Disease', 'start': 185, 'end': 199, 'mesh': 'D011115'}, {'text': 'testicular pain', 'type': 'Disease', 'start': 205, 'end': 220, 'mesh': 'D013733'}, {'text': 'polyarteritis nodosa', 'type': 'Disease', 'start': 456, 'end': 476, 'mesh': 'D010488'}, {'text': 'minocycline', 'type': 'Chemical', 'start': 487, 'end': 498, 'mesh': 'D008911'}, {'text': 'minocycline', 'type': 'Chemical', 'start': 608, 'end': 619, 'mesh': 'D008911'}, {'text': 'vasculitis', 'type': 'Disease', 'start': 628, 'end': 638, 'mesh': 'D014657'}, {'text': 'polyarteritis nodosa', 'type': 'Disease', 'start': 759, 'end': 779, 'mesh': 'D010488'}]"
+1422,16911931,Intramuscular hepatitis B immune globulin combined with lamivudine in prevention of hepatitis B recurrence after liver transplantation.,"BACKGROUND: Combined hepatitis B immune globulin (HBIg) and lamivudine in prophylaxis of the recurrence of hepatitis B after liver transplantation has significantly improved the survival of HBsAg positive patients. This study was undertaken to evaluate the outcomes of liver transplantation for patients with hepatitis B virus (HBV). METHODS: A retrospective chart analysis and a review of the organ transplant database identified 51 patients (43 men and 8 women) transplanted for benign HBV-related cirrhotic diseases between June 2002 and December 2004 who had survived more than 3 months. HBIg was administered intravenously during the first week and intramuscularly thereafter. RESULTS: At a median follow-up of 14.1 months, the overall recurrence rate in the 51 patients was 3.9% (2/51). The overall patient survival was 88.3%, and 82.4% after 1 and 2 years, respectively. A daily oral dose of 100 mg lamivudine for 2 weeks before transplantation for 10 patients enabled 57.1% (4/7) and 62.5% (5/8) of HBV-DNA and HBeAg positive patients respectively to convert to be negative. Intramuscular HBIg was well tolerated in all patients. CONCLUSION: Lamivudine combined with intramuscular HBIg can effectively prevent allograft from the recurrence of HBV after liver transplantation.","[{'text': 'hepatitis B', 'type': 'Disease', 'start': 14, 'end': 25, 'mesh': 'D006509'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 56, 'end': 66, 'mesh': 'D019259'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 84, 'end': 95, 'mesh': 'D006509'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 157, 'end': 168, 'mesh': 'D006509'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 196, 'end': 206, 'mesh': 'D019259'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 243, 'end': 254, 'mesh': 'D006509'}, {'text': 'HBsAg', 'type': 'Chemical', 'start': 326, 'end': 331, 'mesh': 'D006514'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 445, 'end': 456, 'mesh': 'D006509'}, {'text': 'cirrhotic diseases', 'type': 'Disease', 'start': 636, 'end': 654, 'mesh': 'D008103'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 1042, 'end': 1052, 'mesh': 'D019259'}, {'text': 'HBeAg', 'type': 'Chemical', 'start': 1155, 'end': 1160, 'mesh': 'D006513'}, {'text': 'Lamivudine', 'type': 'Chemical', 'start': 1286, 'end': 1296, 'mesh': 'D019259'}]"
+1423,16920333,Anticonvulsant effect of eslicarbazepine acetate (BIA 2-093) on seizures induced by microperfusion of picrotoxin in the hippocampus of freely moving rats.,"Eslicarbazepine acetate (BIA 2-093, S-(-)-10-acetoxy-10,11-dihydro-5H-dibenzo/b,f/azepine-5-carboxamide) is a novel antiepileptic drug, now in Phase III clinical trials, designed with the aim of improving efficacy and safety in comparison with the structurally related drugs carbamazepine (CBZ) and oxcarbazepine (OXC). We have studied the effects of oral treatment with eslicarbazepine acetate on a whole-animal model in which partial seizures can be elicited repeatedly on different days without changes in threshold or seizure patterns. In the animals treated with threshold doses of picrotoxin, the average number of seizures was 2.3+/-1.2, and average seizure duration was 39.5+/-8.4s. Pre-treatment with a dose of 30 mg/kg 2h before picrotoxin microperfusion prevented seizures in the 75% of the rats. Lower doses (3 and 10mg/kg) did not suppress seizures, however, after administration of 10mg/kg, significant reductions in seizures duration (24.3+/-6.8s) and seizure number (1.6+/-0.34) were found. No adverse effects of eslicarbazepine acetate were observed in the behavioral/EEG patterns studied, including sleep/wakefulness cycle, at the doses studied.","[{'text': 'eslicarbazepine acetate', 'type': 'Chemical', 'start': 25, 'end': 48, 'mesh': 'C416835'}, {'text': 'BIA 2-093', 'type': 'Chemical', 'start': 50, 'end': 59, 'mesh': 'C416835'}, {'text': 'seizures', 'type': 'Disease', 'start': 64, 'end': 72, 'mesh': 'D012640'}, {'text': 'picrotoxin', 'type': 'Chemical', 'start': 102, 'end': 112, 'mesh': 'D010852'}, {'text': 'Eslicarbazepine acetate', 'type': 'Chemical', 'start': 155, 'end': 178, 'mesh': 'C416835'}, {'text': 'BIA 2-093', 'type': 'Chemical', 'start': 180, 'end': 189, 'mesh': 'C416835'}, {'text': 'S-(-)-10-acetoxy-10,11-dihydro-5H-dibenzo/b,f/azepine-5-carboxamide', 'type': 'Chemical', 'start': 191, 'end': 258, 'mesh': 'C416835'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 430, 'end': 443, 'mesh': 'D002220'}, {'text': 'CBZ', 'type': 'Chemical', 'start': 445, 'end': 448, 'mesh': 'D002220'}, {'text': 'oxcarbazepine', 'type': 'Chemical', 'start': 454, 'end': 467, 'mesh': 'C036006'}, {'text': 'OXC', 'type': 'Chemical', 'start': 469, 'end': 472, 'mesh': 'C036006'}, {'text': 'eslicarbazepine acetate', 'type': 'Chemical', 'start': 526, 'end': 549, 'mesh': 'C416835'}, {'text': 'seizures', 'type': 'Disease', 'start': 591, 'end': 599, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 677, 'end': 684, 'mesh': 'D012640'}, {'text': 'picrotoxin', 'type': 'Chemical', 'start': 742, 'end': 752, 'mesh': 'D010852'}, {'text': 'seizures', 'type': 'Disease', 'start': 776, 'end': 784, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 812, 'end': 819, 'mesh': 'D012640'}, {'text': 'picrotoxin', 'type': 'Chemical', 'start': 894, 'end': 904, 'mesh': 'D010852'}, {'text': 'seizures', 'type': 'Disease', 'start': 930, 'end': 938, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 1008, 'end': 1016, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 1086, 'end': 1094, 'mesh': 'D012640'}, {'text': 'seizure', 'type': 'Disease', 'start': 1122, 'end': 1129, 'mesh': 'D012640'}, {'text': 'eslicarbazepine acetate', 'type': 'Chemical', 'start': 1184, 'end': 1207, 'mesh': 'C416835'}]"
+1424,17028363,Acute renal failure associated with prolonged intake of slimming pills containing anthraquinones.,"Chinese herbal medicine preparations are widely available and often regarded by the public as natural and safe remedies for a variety of medical conditions. Nephropathy caused by Chinese herbs has previously been reported, usually involving the use of aristolochic acids. We report a 23-year-old woman who developed acute renal failure following prolonged use of a proprietary Chinese herbal slimming pill that contained anthraquinone derivatives, extracted from Rhizoma Rhei (rhubarb). The renal injury was probably aggravated by the concomitant intake of a non-steroidal anti-inflammatory drug, diclofenac. Renal pathology was that of hypocellular interstitial fibrosis. Spontaneous renal recovery occurred upon cessation of the slimming pills, but mild interstitial fibrosis and tubular atrophy was still evident histologically 4 months later. Although a causal relationship between the use of an anthraquinone-containing herbal agent and renal injury remains to be proven, phytotherapy-associated interstitial nephropathy should be considered in patients who present with unexplained renal failure.","[{'text': 'Acute renal failure', 'type': 'Disease', 'start': 0, 'end': 19, 'mesh': 'D058186'}, {'text': 'anthraquinones', 'type': 'Chemical', 'start': 82, 'end': 96, 'mesh': 'D000880'}, {'text': 'Chinese herbal', 'type': 'Chemical', 'start': 98, 'end': 112, 'mesh': 'D004365'}, {'text': 'Nephropathy', 'type': 'Disease', 'start': 255, 'end': 266, 'mesh': 'D007674'}, {'text': 'Chinese herbs', 'type': 'Chemical', 'start': 277, 'end': 290, 'mesh': 'D004365'}, {'text': 'aristolochic acids', 'type': 'Chemical', 'start': 350, 'end': 368, 'mesh': 'D034341'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 414, 'end': 433, 'mesh': 'D058186'}, {'text': 'Chinese herbal', 'type': 'Chemical', 'start': 475, 'end': 489, 'mesh': 'D004365'}, {'text': 'anthraquinone', 'type': 'Chemical', 'start': 519, 'end': 532, 'mesh': 'D000880'}, {'text': 'renal injury', 'type': 'Disease', 'start': 589, 'end': 601, 'mesh': 'D058186'}, {'text': 'diclofenac', 'type': 'Chemical', 'start': 695, 'end': 705, 'mesh': 'D004008'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 761, 'end': 769, 'mesh': 'D005355'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 867, 'end': 875, 'mesh': 'D005355'}, {'text': 'atrophy', 'type': 'Disease', 'start': 888, 'end': 895, 'mesh': 'D001284'}, {'text': 'anthraquinone', 'type': 'Chemical', 'start': 998, 'end': 1011, 'mesh': 'D000880'}, {'text': 'renal injury', 'type': 'Disease', 'start': 1040, 'end': 1052, 'mesh': 'D058186'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1112, 'end': 1123, 'mesh': 'D007674'}, {'text': 'renal failure', 'type': 'Disease', 'start': 1186, 'end': 1199, 'mesh': 'D051437'}]"
+1425,17035713,Chloroacetaldehyde as a sulfhydryl reagent: the role of critical thiol groups in ifosfamide nephropathy.,"Chloroacetaldehyde (CAA) is a metabolite of the alkylating agent ifosfamide (IFO) and putatively responsible for renal damage following anti-tumor therapy with IFO. Depletion of sulfhydryl (SH) groups has been reported from cell culture, animal and clinical studies. In this work the effect of CAA on human proximal tubule cells in primary culture (hRPTEC) was investigated. Toxicity of CAA was determined by protein content, cell number, LDH release, trypan blue exclusion assay and caspase-3 activity. Free thiols were measured by the method of Ellman. CAA reduced hRPTEC cell number and protein, induced a loss in free intracellular thiols and an increase in necrosis markers. CAA but not acrolein inhibited the cysteine proteases caspase-3, caspase-8 and cathepsin B. Caspase activation by cisplatin was inhibited by CAA. In cells stained with fluorescent dyes targeting lysosomes, CAA induced an increase in lysosomal size and lysosomal leakage. The effects of CAA on cysteine protease activities and thiols could be reproduced in cell lysate. Acidification, which slowed the reaction of CAA with thiol donors, could also attenuate effects of CAA on necrosis markers, thiol depletion and cysteine protease inhibition in living cells. Thus, CAA directly reacts with cellular protein and non-protein thiols, mediating its toxicity on hRPTEC. This effect can be reduced by acidification. Therefore, urinary acidification could be an option to prevent IFO nephropathy in patients.","[{'text': 'Chloroacetaldehyde', 'type': 'Chemical', 'start': 0, 'end': 18, 'mesh': 'C004656'}, {'text': 'sulfhydryl', 'type': 'Chemical', 'start': 24, 'end': 34, 'mesh': '-1'}, {'text': 'thiol', 'type': 'Chemical', 'start': 65, 'end': 70, 'mesh': 'D013438'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 81, 'end': 91, 'mesh': 'D007069'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 92, 'end': 103, 'mesh': 'D007674'}, {'text': 'Chloroacetaldehyde', 'type': 'Chemical', 'start': 105, 'end': 123, 'mesh': 'C004656'}, {'text': 'CAA', 'type': 'Chemical', 'start': 125, 'end': 128, 'mesh': 'C004656'}, {'text': 'ifosfamide', 'type': 'Chemical', 'start': 170, 'end': 180, 'mesh': 'D007069'}, {'text': 'IFO', 'type': 'Chemical', 'start': 182, 'end': 185, 'mesh': 'D007069'}, {'text': 'renal damage', 'type': 'Disease', 'start': 218, 'end': 230, 'mesh': 'D007674'}, {'text': 'tumor', 'type': 'Disease', 'start': 246, 'end': 251, 'mesh': 'D009369'}, {'text': 'IFO', 'type': 'Chemical', 'start': 265, 'end': 268, 'mesh': 'D007069'}, {'text': 'sulfhydryl', 'type': 'Chemical', 'start': 283, 'end': 293, 'mesh': '-1'}, {'text': 'SH', 'type': 'Chemical', 'start': 295, 'end': 297, 'mesh': '-1'}, {'text': 'CAA', 'type': 'Chemical', 'start': 399, 'end': 402, 'mesh': 'C004656'}, {'text': 'Toxicity', 'type': 'Disease', 'start': 480, 'end': 488, 'mesh': 'D064420'}, {'text': 'CAA', 'type': 'Chemical', 'start': 492, 'end': 495, 'mesh': 'C004656'}, {'text': 'trypan blue', 'type': 'Chemical', 'start': 557, 'end': 568, 'mesh': 'D014343'}, {'text': 'thiols', 'type': 'Chemical', 'start': 614, 'end': 620, 'mesh': 'D013438'}, {'text': 'CAA', 'type': 'Chemical', 'start': 660, 'end': 663, 'mesh': 'C004656'}, {'text': 'thiols', 'type': 'Chemical', 'start': 741, 'end': 747, 'mesh': 'D013438'}, {'text': 'necrosis', 'type': 'Disease', 'start': 767, 'end': 775, 'mesh': 'D009336'}, {'text': 'CAA', 'type': 'Chemical', 'start': 785, 'end': 788, 'mesh': 'C004656'}, {'text': 'acrolein', 'type': 'Chemical', 'start': 797, 'end': 805, 'mesh': 'D000171'}, {'text': 'cysteine', 'type': 'Chemical', 'start': 820, 'end': 828, 'mesh': 'D003545'}, {'text': 'cisplatin', 'type': 'Chemical', 'start': 899, 'end': 908, 'mesh': 'D002945'}, {'text': 'CAA', 'type': 'Chemical', 'start': 926, 'end': 929, 'mesh': 'C004656'}, {'text': 'CAA', 'type': 'Chemical', 'start': 991, 'end': 994, 'mesh': 'C004656'}, {'text': 'CAA', 'type': 'Chemical', 'start': 1071, 'end': 1074, 'mesh': 'C004656'}, {'text': 'cysteine', 'type': 'Chemical', 'start': 1078, 'end': 1086, 'mesh': 'D003545'}, {'text': 'thiols', 'type': 'Chemical', 'start': 1111, 'end': 1117, 'mesh': 'D013438'}, {'text': 'CAA', 'type': 'Chemical', 'start': 1198, 'end': 1201, 'mesh': 'C004656'}, {'text': 'thiol', 'type': 'Chemical', 'start': 1207, 'end': 1212, 'mesh': 'D013438'}, {'text': 'CAA', 'type': 'Chemical', 'start': 1253, 'end': 1256, 'mesh': 'C004656'}, {'text': 'necrosis', 'type': 'Disease', 'start': 1260, 'end': 1268, 'mesh': 'D009336'}, {'text': 'thiol', 'type': 'Chemical', 'start': 1278, 'end': 1283, 'mesh': 'D013438'}, {'text': 'cysteine', 'type': 'Chemical', 'start': 1298, 'end': 1306, 'mesh': 'D003545'}, {'text': 'CAA', 'type': 'Chemical', 'start': 1350, 'end': 1353, 'mesh': 'C004656'}, {'text': 'thiols', 'type': 'Chemical', 'start': 1408, 'end': 1414, 'mesh': 'D013438'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1430, 'end': 1438, 'mesh': 'D064420'}, {'text': 'IFO', 'type': 'Chemical', 'start': 1558, 'end': 1561, 'mesh': 'D007069'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1562, 'end': 1573, 'mesh': 'D007674'}]"
+1426,17042797,Stereological methods reveal the robust size and stability of ectopic hilar granule cells after pilocarpine-induced status epilepticus in the adult rat.,"Following status epilepticus in the rat, dentate granule cell neurogenesis increases greatly, and many of the new neurons appear to develop ectopically, in the hilar region of the hippocampal formation. It has been suggested that the ectopic hilar granule cells could contribute to the spontaneous seizures that ultimately develop after status epilepticus. However, the population has never been quantified, so it is unclear whether it is substantial enough to have a strong influence on epileptogenesis. To quantify this population, the total number of ectopic hilar granule cells was estimated using unbiased stereology at different times after pilocarpine-induced status epilepticus. The number of hilar neurons immunoreactive for Prox-1, a granule-cell-specific marker, was estimated using the optical fractionator method. The results indicate that the size of the hilar ectopic granule cell population after status epilepticus is substantial, and stable over time. Interestingly, the size of the population appears to be correlated with the frequency of behavioral seizures, because animals with more ectopic granule cells in the hilus have more frequent behavioral seizures. The hilar ectopic granule cell population does not appear to vary systematically across the septotemporal axis, although it is associated with an increase in volume of the hilus. The results provide new insight into the potential role of ectopic hilar granule cells in the pilocarpine model of temporal lobe epilepsy.","[{'text': 'pilocarpine', 'type': 'Chemical', 'start': 96, 'end': 107, 'mesh': 'D010862'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 116, 'end': 134, 'mesh': 'D013226'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 163, 'end': 181, 'mesh': 'D013226'}, {'text': 'seizures', 'type': 'Disease', 'start': 451, 'end': 459, 'mesh': 'D012640'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 490, 'end': 508, 'mesh': 'D013226'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 800, 'end': 811, 'mesh': 'D010862'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 820, 'end': 838, 'mesh': 'D013226'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 1066, 'end': 1084, 'mesh': 'D013226'}, {'text': 'seizures', 'type': 'Disease', 'start': 1223, 'end': 1231, 'mesh': 'D012640'}, {'text': 'seizures', 'type': 'Disease', 'start': 1324, 'end': 1332, 'mesh': 'D012640'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1607, 'end': 1618, 'mesh': 'D010862'}, {'text': 'temporal lobe epilepsy', 'type': 'Disease', 'start': 1628, 'end': 1650, 'mesh': 'D004833'}]"
+1427,17069550,"A prospective, open-label trial of galantamine in autistic disorder.","OBJECTIVE: Post-mortem studies have reported abnormalities of the cholinergic system in autism. The purpose of this study was to assess the use of galantamine, an acetylcholinesterase inhibitor and nicotinic receptor modulator, in the treatment of interfering behaviors in children with autism. METHODS: Thirteen medication-free children with autism (mean age, 8.8 +/- 3.5 years) participated in a 12-week, open-label trial of galantamine. Patients were rated monthly by parents on the Aberrant Behavior Checklist (ABC) and the Conners' Parent Rating Scale-Revised, and by a physician using the Children's Psychiatric Rating Scale and the Clinical Global Impressions scale. RESULTS: Patients showed a significant reduction in parent-rated irritability and social withdrawal on the ABC as well as significant improvements in emotional lability and inattention on the Conners' Parent Rating Scale--Revised. Similarly, clinician ratings showed reductions in the anger subscale of the Children's Psychiatric Rating Scale. Eight of 13 participants were rated as responders on the basis of their improvement scores on the Clinical Global Impressions scale. Overall, galantamine was well-tolerated, with no significant adverse effects apart from headaches in one patient. CONCLUSION: In this open trial, galantamine was well-tolerated and appeared to be beneficial for the treatment of interfering behaviors in children with autism, particularly aggression, behavioral dyscontrol, and inattention. Further controlled trials are warranted.","[{'text': 'galantamine', 'type': 'Chemical', 'start': 35, 'end': 46, 'mesh': 'D005702'}, {'text': 'autistic disorder', 'type': 'Disease', 'start': 50, 'end': 67, 'mesh': 'D001321'}, {'text': 'autism', 'type': 'Disease', 'start': 157, 'end': 163, 'mesh': 'D001321'}, {'text': 'galantamine', 'type': 'Chemical', 'start': 216, 'end': 227, 'mesh': 'D005702'}, {'text': 'autism', 'type': 'Disease', 'start': 356, 'end': 362, 'mesh': 'D001321'}, {'text': 'autism', 'type': 'Disease', 'start': 412, 'end': 418, 'mesh': 'D001321'}, {'text': 'galantamine', 'type': 'Chemical', 'start': 496, 'end': 507, 'mesh': 'D005702'}, {'text': 'irritability', 'type': 'Disease', 'start': 808, 'end': 820, 'mesh': 'D001523'}, {'text': 'galantamine', 'type': 'Chemical', 'start': 1229, 'end': 1240, 'mesh': 'D005702'}, {'text': 'headaches', 'type': 'Disease', 'start': 1308, 'end': 1317, 'mesh': 'D006261'}, {'text': 'galantamine', 'type': 'Chemical', 'start': 1366, 'end': 1377, 'mesh': 'D005702'}, {'text': 'autism', 'type': 'Disease', 'start': 1487, 'end': 1493, 'mesh': 'D001321'}, {'text': 'aggression', 'type': 'Disease', 'start': 1508, 'end': 1518, 'mesh': 'D001523'}, {'text': 'behavioral dyscontrol', 'type': 'Disease', 'start': 1520, 'end': 1541, 'mesh': 'D002653'}, {'text': 'inattention', 'type': 'Disease', 'start': 1547, 'end': 1558, 'mesh': 'D019958'}]"
+1428,17151160,Randomized comparison of olanzapine versus risperidone for the treatment of first-episode schizophrenia: 4-month outcomes.,"OBJECTIVE: The authors compared 4-month treatment outcomes for olanzapine versus risperidone in patients with first-episode schizophrenia spectrum disorders. METHOD: One hundred twelve subjects (70% male; mean age=23.3 years [SD = 5.1]) with first-episode schizophrenia (75%), schizophreniform disorder (17%), or schizoaffective disorder (8%) were randomly assigned to treatment with olanzapine (2.5-20 mg/day) or risperidone (1-6 mg/day). RESULTS: Response rates did not significantly differ between olanzapine (43.7%, 95% CI=28.8%-58.6%) and risperidone (54.3%, 95% CI=39.9%-68.7%). Among those responding to treatment, more subjects in the olanzapine group (40.9%, 95% CI=16.8%-65.0%) than in the risperidone group (18.9%, 95% CI=0%-39.2%) had subsequent ratings not meeting response criteria. Negative symptom outcomes and measures of parkinsonism and akathisia did not differ between medications. Extrapyramidal symptom severity scores were 1.4 (95% CI=1.2-1.6) with risperidone and 1.2 (95% CI=1.0-1.4) with olanzapine. Significantly more weight gain occurred with olanzapine than with risperidone: the increase in weight at 4 months relative to baseline weight was 17.3% (95% CI=14.2%-20.5%) with olanzapine and 11.3% (95% CI=8.4%-14.3%) with risperidone. Body mass index at baseline and at 4 months was 24.3 (95% CI=22.8-25.7) versus 28.2 (95% CI=26.7-29.7) with olanzapine and 23.9 (95% CI=22.5-25.3) versus 26.7 (95% CI=25.2-28.2) with risperidone. CONCLUSIONS: Clinical outcomes with risperidone were equal to those with olanzapine, and response may be more stable. Olanzapine may have an advantage for motor side effects. Both medications caused substantial rapid weight gain, but weight gain was greater with olanzapine.","[{'text': 'olanzapine', 'type': 'Chemical', 'start': 25, 'end': 35, 'mesh': 'C076029'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 43, 'end': 54, 'mesh': 'D018967'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 90, 'end': 103, 'mesh': 'D012559'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 186, 'end': 196, 'mesh': 'C076029'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 204, 'end': 215, 'mesh': 'D018967'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 247, 'end': 260, 'mesh': 'D012559'}, {'text': 'schizophrenia', 'type': 'Disease', 'start': 379, 'end': 392, 'mesh': 'D012559'}, {'text': 'schizophreniform disorder', 'type': 'Disease', 'start': 400, 'end': 425, 'mesh': 'D011618'}, {'text': 'schizoaffective disorder', 'type': 'Disease', 'start': 436, 'end': 460, 'mesh': 'D011618'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 507, 'end': 517, 'mesh': 'C076029'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 537, 'end': 548, 'mesh': 'D018967'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 624, 'end': 634, 'mesh': 'C076029'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 667, 'end': 678, 'mesh': 'D018967'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 766, 'end': 776, 'mesh': 'C076029'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 823, 'end': 834, 'mesh': 'D018967'}, {'text': 'parkinsonism', 'type': 'Disease', 'start': 962, 'end': 974, 'mesh': 'D010302'}, {'text': 'akathisia', 'type': 'Disease', 'start': 979, 'end': 988, 'mesh': 'D017109'}, {'text': 'Extrapyramidal symptom', 'type': 'Disease', 'start': 1025, 'end': 1047, 'mesh': 'D001480'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 1095, 'end': 1106, 'mesh': 'D018967'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 1137, 'end': 1147, 'mesh': 'C076029'}, {'text': 'weight gain', 'type': 'Disease', 'start': 1168, 'end': 1179, 'mesh': 'D015430'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 1194, 'end': 1204, 'mesh': 'C076029'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 1215, 'end': 1226, 'mesh': 'D018967'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 1327, 'end': 1337, 'mesh': 'C076029'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 1373, 'end': 1384, 'mesh': 'D018967'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 1494, 'end': 1504, 'mesh': 'C076029'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 1569, 'end': 1580, 'mesh': 'D018967'}, {'text': 'risperidone', 'type': 'Chemical', 'start': 1618, 'end': 1629, 'mesh': 'D018967'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 1655, 'end': 1665, 'mesh': 'C076029'}, {'text': 'Olanzapine', 'type': 'Chemical', 'start': 1700, 'end': 1710, 'mesh': 'C076029'}, {'text': 'weight gain', 'type': 'Disease', 'start': 1799, 'end': 1810, 'mesh': 'D015430'}, {'text': 'weight gain', 'type': 'Disease', 'start': 1816, 'end': 1827, 'mesh': 'D015430'}, {'text': 'olanzapine', 'type': 'Chemical', 'start': 1845, 'end': 1855, 'mesh': 'C076029'}]"
+1429,17159032,Early paracentral visual field loss in patients taking hydroxychloroquine.,"OBJECTIVE: To review the natural history and ocular and systemic adverse effects of patients taking hydroxychloroquine sulfate who attended an ophthalmic screening program. DESIGN: Retrospective study. RESULTS: Records of 262 patients who were taking hydroxychloroquine and screened in the Department of Ophthalmology were reviewed. Of the 262 patients, 14 (18%) of 76 who had stopped treatment at the time of the study experienced documented adverse effects. Systemic adverse effects occurred in 8 patients (10.5%) and ocular adverse effects, in 5 (6.5%). Thirty-five patients (13.4%) had visual field abnormalities, which were attributed to hydroxychloroquine treatment in 4 patients (1.5%). Three of the 4 patients were taking less than 6.5 mg/kg per day and all patients had normal renal and liver function test results. CONCLUSIONS: The current study used a protocol of visual acuity and color vision assessment, funduscopy, and Humphrey 10-2 visual field testing and shows that visual field defects appeared before any corresponding changes in any other tested clinical parameters; the defects were reproducible and the test parameters were reliable. Patients taking hydroxychloroquine can demonstrate a toxic reaction in the retina despite the absence of known risk factors. Screening, including Humphrey 10-2 visual field assessment, is recommended 2 years after the initial baseline and yearly thereafter.","[{'text': 'visual field loss', 'type': 'Disease', 'start': 18, 'end': 35, 'mesh': 'D014786'}, {'text': 'hydroxychloroquine', 'type': 'Chemical', 'start': 55, 'end': 73, 'mesh': 'D006886'}, {'text': 'hydroxychloroquine sulfate', 'type': 'Chemical', 'start': 175, 'end': 201, 'mesh': 'D006886'}, {'text': 'hydroxychloroquine', 'type': 'Chemical', 'start': 326, 'end': 344, 'mesh': 'D006886'}, {'text': 'visual field abnormalities', 'type': 'Disease', 'start': 665, 'end': 691, 'mesh': 'D014786'}, {'text': 'hydroxychloroquine', 'type': 'Chemical', 'start': 718, 'end': 736, 'mesh': 'D006886'}, {'text': 'visual field defects', 'type': 'Disease', 'start': 1059, 'end': 1079, 'mesh': 'D014786'}, {'text': 'hydroxychloroquine', 'type': 'Chemical', 'start': 1248, 'end': 1266, 'mesh': 'D006886'}]"
+1430,17223814,Peri-operative atrioventricular block as a result of chemotherapy with epirubicin and paclitaxel.,"A 47-year-old woman presented for mastectomy and immediate latissimus dorsi flap reconstruction having been diagnosed with carcinoma of the breast 6 months previously. In the preceding months she had received neo-adjuvant chemotherapy with epirubicin, paclitaxel (Taxol) and cyclophosphamide. This had been apparently uncomplicated and she had maintained a remarkably high level of physical activity. She was found to be bradycardic at pre-operative assessment but had no cardiac symptoms. Second degree Mobitz type II atrioventricular block was diagnosed on electrocardiogram, and temporary transvenous ventricular pacing instituted in the peri-operative period. We discuss how evidence-based guidelines would not have been helpful in this case, and how chemotherapy can exhibit substantial cardiotoxicity that may develop over many years. We suggest that patients who have received chemotherapy at any time should have a pre-operative electrocardiogram even if they are asymptomatic.","[{'text': 'atrioventricular block', 'type': 'Disease', 'start': 15, 'end': 37, 'mesh': 'D054537'}, {'text': 'epirubicin', 'type': 'Chemical', 'start': 71, 'end': 81, 'mesh': 'D015251'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 86, 'end': 96, 'mesh': 'D017239'}, {'text': 'carcinoma of the breast', 'type': 'Disease', 'start': 221, 'end': 244, 'mesh': 'D001943'}, {'text': 'epirubicin', 'type': 'Chemical', 'start': 338, 'end': 348, 'mesh': 'D015251'}, {'text': 'paclitaxel', 'type': 'Chemical', 'start': 350, 'end': 360, 'mesh': 'D017239'}, {'text': 'Taxol', 'type': 'Chemical', 'start': 362, 'end': 367, 'mesh': 'D017239'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 373, 'end': 389, 'mesh': 'D003520'}, {'text': 'bradycardic', 'type': 'Disease', 'start': 519, 'end': 530, 'mesh': 'D001919'}, {'text': 'atrioventricular block', 'type': 'Disease', 'start': 617, 'end': 639, 'mesh': 'D054537'}, {'text': 'cardiotoxicity', 'type': 'Disease', 'start': 890, 'end': 904, 'mesh': 'D066126'}]"
+1431,17255138,Risks and benefits of COX-2 inhibitors vs non-selective NSAIDs: does their cardiovascular risk exceed their gastrointestinal benefit? A retrospective cohort study.,"OBJECTIVES: The risk of acute myocardial infarction (AMI) with COX-2 inhibitors may offset their gastrointestinal (GI) benefit compared with non-selective (NS) non-steroidal anti-inflammatory drugs (NSAIDs). We aimed to compare the risks of hospitalization for AMI and GI bleeding among elderly patients using COX-2 inhibitors, NS-NSAIDs and acetaminophen. METHODS: We conducted a retrospective cohort study using administrative data of patients > or =65 years of age who filled a prescription for NSAID or acetaminophen during 1999-2002. Outcomes were compared using Cox regression models with time-dependent exposures. RESULTS: Person-years of exposure among non-users of aspirin were: 75,761 to acetaminophen, 42,671 to rofecoxib 65,860 to celecoxib, and 37,495 to NS-NSAIDs. Among users of aspirin, they were: 14,671 to rofecoxib, 22,875 to celecoxib, 9,832 to NS-NSAIDs and 38,048 to acetaminophen. Among non-users of aspirin, the adjusted hazard ratios (95% confidence interval) of hospitalization for AMI/GI vs the acetaminophen (with no aspirin) group were: rofecoxib 1.27 (1.13, 1.42), celecoxib 0.93 (0.83, 1.03), naproxen 1.59 (1.31, 1.93), diclofenac 1.17 (0.99, 1.38) and ibuprofen 1.05 (0.74, 1.51). Among users of aspirin, they were: rofecoxib 1.73 (1.52, 1.98), celecoxib 1.34 (1.19, 1.52), ibuprofen 1.51 (0.95, 2.41), diclofenac 1.69 (1.35, 2.10), naproxen 1.35 (0.97, 1.88) and acetaminophen 1.29 (1.17, 1.42). CONCLUSION: Among non-users of aspirin, naproxen seemed to carry the highest risk for AMI/GI bleeding. The AMI/GI toxicity of celecoxib was similar to that of acetaminophen and seemed to be better than those of rofecoxib and NS-NSAIDs. Among users of aspirin, both celecoxib and naproxen seemed to be the least toxic.","[{'text': 'COX-2 inhibitors', 'type': 'Chemical', 'start': 22, 'end': 38, 'mesh': 'D052246'}, {'text': 'acute myocardial infarction', 'type': 'Disease', 'start': 188, 'end': 215, 'mesh': 'D009203'}, {'text': 'AMI', 'type': 'Disease', 'start': 217, 'end': 220, 'mesh': 'D009203'}, {'text': 'COX-2 inhibitors', 'type': 'Chemical', 'start': 227, 'end': 243, 'mesh': 'D052246'}, {'text': 'non-steroidal anti-inflammatory drugs', 'type': 'Chemical', 'start': 324, 'end': 361, 'mesh': 'D000894'}, {'text': 'AMI', 'type': 'Disease', 'start': 425, 'end': 428, 'mesh': 'D009203'}, {'text': 'GI bleeding', 'type': 'Disease', 'start': 433, 'end': 444, 'mesh': 'D006471'}, {'text': 'COX-2 inhibitors', 'type': 'Chemical', 'start': 474, 'end': 490, 'mesh': 'D052246'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 506, 'end': 519, 'mesh': 'D000082'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 671, 'end': 684, 'mesh': 'D000082'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 838, 'end': 845, 'mesh': 'D001241'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 862, 'end': 875, 'mesh': 'D000082'}, {'text': 'rofecoxib', 'type': 'Chemical', 'start': 887, 'end': 896, 'mesh': 'C116926'}, {'text': 'celecoxib', 'type': 'Chemical', 'start': 907, 'end': 916, 'mesh': 'C105934'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 958, 'end': 965, 'mesh': 'D001241'}, {'text': 'rofecoxib', 'type': 'Chemical', 'start': 988, 'end': 997, 'mesh': 'C116926'}, {'text': 'celecoxib', 'type': 'Chemical', 'start': 1009, 'end': 1018, 'mesh': 'C105934'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 1053, 'end': 1066, 'mesh': 'D000082'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1087, 'end': 1094, 'mesh': 'D001241'}, {'text': 'AMI', 'type': 'Disease', 'start': 1172, 'end': 1175, 'mesh': 'D009203'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 1186, 'end': 1199, 'mesh': 'D000082'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1209, 'end': 1216, 'mesh': 'D001241'}, {'text': 'rofecoxib', 'type': 'Chemical', 'start': 1230, 'end': 1239, 'mesh': 'C116926'}, {'text': 'celecoxib', 'type': 'Chemical', 'start': 1259, 'end': 1268, 'mesh': 'C105934'}, {'text': 'naproxen', 'type': 'Chemical', 'start': 1288, 'end': 1296, 'mesh': 'D009288'}, {'text': 'diclofenac', 'type': 'Chemical', 'start': 1316, 'end': 1326, 'mesh': 'D004008'}, {'text': 'ibuprofen', 'type': 'Chemical', 'start': 1349, 'end': 1358, 'mesh': 'D007052'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1393, 'end': 1400, 'mesh': 'D001241'}, {'text': 'rofecoxib', 'type': 'Chemical', 'start': 1413, 'end': 1422, 'mesh': 'C116926'}, {'text': 'celecoxib', 'type': 'Chemical', 'start': 1442, 'end': 1451, 'mesh': 'C105934'}, {'text': 'ibuprofen', 'type': 'Chemical', 'start': 1471, 'end': 1480, 'mesh': 'D007052'}, {'text': 'diclofenac', 'type': 'Chemical', 'start': 1500, 'end': 1510, 'mesh': 'D004008'}, {'text': 'naproxen', 'type': 'Chemical', 'start': 1530, 'end': 1538, 'mesh': 'D009288'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 1561, 'end': 1574, 'mesh': 'D000082'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1625, 'end': 1632, 'mesh': 'D001241'}, {'text': 'naproxen', 'type': 'Chemical', 'start': 1634, 'end': 1642, 'mesh': 'D009288'}, {'text': 'AMI', 'type': 'Disease', 'start': 1680, 'end': 1683, 'mesh': 'D009203'}, {'text': 'GI bleeding', 'type': 'Disease', 'start': 1684, 'end': 1695, 'mesh': 'D006471'}, {'text': 'AMI', 'type': 'Disease', 'start': 1701, 'end': 1704, 'mesh': 'D009203'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1708, 'end': 1716, 'mesh': 'D064420'}, {'text': 'celecoxib', 'type': 'Chemical', 'start': 1720, 'end': 1729, 'mesh': 'C105934'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 1753, 'end': 1766, 'mesh': 'D000082'}, {'text': 'rofecoxib', 'type': 'Chemical', 'start': 1805, 'end': 1814, 'mesh': 'C116926'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1845, 'end': 1852, 'mesh': 'D001241'}, {'text': 'celecoxib', 'type': 'Chemical', 'start': 1859, 'end': 1868, 'mesh': 'C105934'}, {'text': 'naproxen', 'type': 'Chemical', 'start': 1873, 'end': 1881, 'mesh': 'D009288'}]"
+1432,17297207,Quinine-induced arrhythmia in a patient with severe malaria.,"It was reported that there was a case of severe malaria patient with jaundice who presented with arrhythmia (premature ventricular contraction) while getting quinine infusion was reported. A man, 25 years old, was admitted to hospital with high fever, chill, vomiting, jaundice. The patient was fully conscious, blood pressure 120/80 mmHg, pulse rate 100 x/minute, regular. On admission, laboratory examination showed Plasmodium falciparum (++++), total bilirubin 8.25 mg/dL, conjugated bilirubin 4.36 mg/dL, unconjugated bilirubin 3.89 mg/dL, potassium 3.52 meq/L Patient was diagnosed as severe malaria with jaundice and got quinine infusion in dextrose 5% 500 mg/8 hour. On the second day the patient had vomitus, diarrhea, tinnitus, loss of hearing. After 30 hours of quinine infusion the patient felt palpitation and electrocardiography (ECG) recording showed premature ventricular contraction (PVC) > 5 x/minute, trigemini, constant type--sinoatrial block, positive U wave. He was treated with lidocaine 50 mg intravenously followed by infusion 1500 mg in dextrose 5%/24 hour and potassium aspartate tablet. Quinine infusion was discontinued and changed with sulfate quinine tablets. Three hours later the patient felt better, the frequency of PVC reduced to 4 - 5 x/minute and on the third day ECG was normal, potassium level was 3.34 meq/L. He was discharged on 7th day in good condition. Quinine, like quinidine, is a chincona alkaloid that has anti-arrhythmic property, although it also pro-arrhythmic that can cause various arrhythmias, including severe arrhythmia such as multiple PVC. Administration of parenteral quinine must be done carefully and with good observation because of its pro-arrhythmic effect, especially in older patients who have heart diseases or patients with electrolyte disorder (hypokalemia) which frequently occurs due to vomiting and or diarrhea in malaria cases.","[{'text': 'Quinine', 'type': 'Chemical', 'start': 0, 'end': 7, 'mesh': 'D011803'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 16, 'end': 26, 'mesh': 'D001145'}, {'text': 'severe malaria', 'type': 'Disease', 'start': 45, 'end': 59, 'mesh': 'D016778'}, {'text': 'severe malaria', 'type': 'Disease', 'start': 102, 'end': 116, 'mesh': 'D016778'}, {'text': 'jaundice', 'type': 'Disease', 'start': 130, 'end': 138, 'mesh': 'D007565'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 158, 'end': 168, 'mesh': 'D001145'}, {'text': 'premature ventricular contraction', 'type': 'Disease', 'start': 170, 'end': 203, 'mesh': 'D018879'}, {'text': 'quinine', 'type': 'Chemical', 'start': 219, 'end': 226, 'mesh': 'D011803'}, {'text': 'fever', 'type': 'Disease', 'start': 306, 'end': 311, 'mesh': 'D005334'}, {'text': 'chill', 'type': 'Disease', 'start': 313, 'end': 318, 'mesh': 'D023341'}, {'text': 'vomiting', 'type': 'Disease', 'start': 320, 'end': 328, 'mesh': 'D014839'}, {'text': 'jaundice', 'type': 'Disease', 'start': 330, 'end': 338, 'mesh': 'D007565'}, {'text': 'bilirubin', 'type': 'Chemical', 'start': 515, 'end': 524, 'mesh': 'D001663'}, {'text': 'bilirubin', 'type': 'Chemical', 'start': 548, 'end': 557, 'mesh': 'D001663'}, {'text': 'bilirubin', 'type': 'Chemical', 'start': 583, 'end': 592, 'mesh': 'D001663'}, {'text': 'potassium', 'type': 'Chemical', 'start': 605, 'end': 614, 'mesh': 'D011188'}, {'text': 'severe malaria', 'type': 'Disease', 'start': 651, 'end': 665, 'mesh': 'D016778'}, {'text': 'jaundice', 'type': 'Disease', 'start': 671, 'end': 679, 'mesh': 'D007565'}, {'text': 'quinine', 'type': 'Chemical', 'start': 688, 'end': 695, 'mesh': 'D011803'}, {'text': 'dextrose', 'type': 'Chemical', 'start': 708, 'end': 716, 'mesh': 'D005947'}, {'text': 'vomitus', 'type': 'Disease', 'start': 769, 'end': 776, 'mesh': 'D014839'}, {'text': 'diarrhea', 'type': 'Disease', 'start': 778, 'end': 786, 'mesh': 'D003967'}, {'text': 'tinnitus', 'type': 'Disease', 'start': 788, 'end': 796, 'mesh': 'D014012'}, {'text': 'loss of hearing', 'type': 'Disease', 'start': 798, 'end': 813, 'mesh': 'D034381'}, {'text': 'quinine', 'type': 'Chemical', 'start': 833, 'end': 840, 'mesh': 'D011803'}, {'text': 'palpitation', 'type': 'Disease', 'start': 867, 'end': 878, 'mesh': '-1'}, {'text': 'premature ventricular contraction', 'type': 'Disease', 'start': 926, 'end': 959, 'mesh': 'D018879'}, {'text': 'PVC', 'type': 'Disease', 'start': 961, 'end': 964, 'mesh': 'D018879'}, {'text': 'sinoatrial block', 'type': 'Disease', 'start': 1006, 'end': 1022, 'mesh': 'D012848'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 1061, 'end': 1070, 'mesh': 'D008012'}, {'text': 'dextrose', 'type': 'Chemical', 'start': 1123, 'end': 1131, 'mesh': 'D005947'}, {'text': 'potassium aspartate', 'type': 'Chemical', 'start': 1147, 'end': 1166, 'mesh': 'D001224'}, {'text': 'Quinine', 'type': 'Chemical', 'start': 1175, 'end': 1182, 'mesh': 'D011803'}, {'text': 'quinine', 'type': 'Chemical', 'start': 1234, 'end': 1241, 'mesh': 'D011803'}, {'text': 'PVC', 'type': 'Disease', 'start': 1311, 'end': 1314, 'mesh': 'D018879'}, {'text': 'potassium', 'type': 'Chemical', 'start': 1378, 'end': 1387, 'mesh': 'D011188'}, {'text': 'Quinine', 'type': 'Chemical', 'start': 1458, 'end': 1465, 'mesh': 'D011803'}, {'text': 'quinidine', 'type': 'Chemical', 'start': 1472, 'end': 1481, 'mesh': 'D011802'}, {'text': 'arrhythmic', 'type': 'Disease', 'start': 1520, 'end': 1530, 'mesh': 'D001145'}, {'text': 'arrhythmic', 'type': 'Disease', 'start': 1562, 'end': 1572, 'mesh': 'D001145'}, {'text': 'arrhythmias', 'type': 'Disease', 'start': 1596, 'end': 1607, 'mesh': 'D001145'}, {'text': 'arrhythmia', 'type': 'Disease', 'start': 1626, 'end': 1636, 'mesh': 'D001145'}, {'text': 'PVC', 'type': 'Disease', 'start': 1654, 'end': 1657, 'mesh': 'D018879'}, {'text': 'quinine', 'type': 'Chemical', 'start': 1688, 'end': 1695, 'mesh': 'D011803'}, {'text': 'arrhythmic', 'type': 'Disease', 'start': 1764, 'end': 1774, 'mesh': 'D001145'}, {'text': 'heart diseases', 'type': 'Disease', 'start': 1821, 'end': 1835, 'mesh': 'D006331'}, {'text': 'electrolyte disorder', 'type': 'Disease', 'start': 1853, 'end': 1873, 'mesh': 'D014883'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 1875, 'end': 1886, 'mesh': 'D007008'}, {'text': 'vomiting', 'type': 'Disease', 'start': 1919, 'end': 1927, 'mesh': 'D014839'}, {'text': 'diarrhea', 'type': 'Disease', 'start': 1935, 'end': 1943, 'mesh': 'D003967'}, {'text': 'malaria', 'type': 'Disease', 'start': 1947, 'end': 1954, 'mesh': 'D008288'}]"
+1433,17346443,"Penicillamine-related lichenoid dermatitis and utility of zinc acetate in a Wilson disease patient with hepatic presentation, anxiety and SPECT abnormalities.","Wilson's disease is an autosomal recessive disorder of hepatic copper metabolism with consequent copper accumulation and toxicity in many tissues and consequent hepatic, neurologic and psychiatric disorders. We report a case of Wilson's disease with chronic liver disease; moreover, in our patient, presenting also with high levels of state anxiety without depression, 99mTc-ECD-SPECT showed cortical hypoperfusion in frontal lobes, more marked on the left frontal lobe. During the follow-up of our patient, penicillamine was interrupted after the appearance of a lichenoid dermatitis, and zinc acetate permitted to continue the successful treatment of the patient without side-effects. In our case the therapy with zinc acetate represented an effective treatment for a Wilson's disease patient in which penicillamine-related side effects appeared. The safety of the zinc acetate allowed us to avoid other potentially toxic chelating drugs; this observation is in line with the growing evidence on the efficacy of the drug in the treatment of Wilson's disease. Since most of Wilson's disease penicillamine-treated patients do not seem to develop this skin lesion, it could be conceivable that a specific genetic factor is involved in drug response. Further studies are needed for a better clarification of Wilson's disease therapy, and in particular to differentiate specific therapies for different Wilson's disease phenotypes.","[{'text': 'Penicillamine', 'type': 'Chemical', 'start': 0, 'end': 13, 'mesh': 'D010396'}, {'text': 'lichenoid dermatitis', 'type': 'Disease', 'start': 22, 'end': 42, 'mesh': 'D017512'}, {'text': 'zinc acetate', 'type': 'Chemical', 'start': 58, 'end': 70, 'mesh': 'D019345'}, {'text': 'Wilson disease', 'type': 'Disease', 'start': 76, 'end': 90, 'mesh': 'D006527'}, {'text': 'anxiety', 'type': 'Disease', 'start': 126, 'end': 133, 'mesh': 'D001008'}, {'text': ""Wilson's disease"", 'type': 'Disease', 'start': 159, 'end': 175, 'mesh': 'D006527'}, {'text': 'copper', 'type': 'Chemical', 'start': 222, 'end': 228, 'mesh': 'D003300'}, {'text': 'copper', 'type': 'Chemical', 'start': 256, 'end': 262, 'mesh': 'D003300'}, {'text': 'toxicity', 'type': 'Disease', 'start': 280, 'end': 288, 'mesh': 'D064420'}, {'text': ""Wilson's disease"", 'type': 'Disease', 'start': 387, 'end': 403, 'mesh': 'D006527'}, {'text': 'chronic liver disease', 'type': 'Disease', 'start': 409, 'end': 430, 'mesh': 'D008107'}, {'text': 'anxiety', 'type': 'Disease', 'start': 500, 'end': 507, 'mesh': 'D001008'}, {'text': 'depression', 'type': 'Disease', 'start': 516, 'end': 526, 'mesh': 'D003866'}, {'text': 'penicillamine', 'type': 'Chemical', 'start': 667, 'end': 680, 'mesh': 'D010396'}, {'text': 'lichenoid dermatitis', 'type': 'Disease', 'start': 723, 'end': 743, 'mesh': 'D017512'}, {'text': 'zinc acetate', 'type': 'Chemical', 'start': 749, 'end': 761, 'mesh': 'D019345'}, {'text': 'zinc acetate', 'type': 'Chemical', 'start': 875, 'end': 887, 'mesh': 'D019345'}, {'text': ""Wilson's disease"", 'type': 'Disease', 'start': 929, 'end': 945, 'mesh': 'D006527'}, {'text': 'penicillamine', 'type': 'Chemical', 'start': 963, 'end': 976, 'mesh': 'D010396'}, {'text': 'zinc acetate', 'type': 'Chemical', 'start': 1026, 'end': 1038, 'mesh': 'D019345'}, {'text': ""Wilson's disease"", 'type': 'Disease', 'start': 1202, 'end': 1218, 'mesh': 'D006527'}, {'text': ""Wilson's disease"", 'type': 'Disease', 'start': 1234, 'end': 1250, 'mesh': 'D006527'}, {'text': 'penicillamine', 'type': 'Chemical', 'start': 1251, 'end': 1264, 'mesh': 'D010396'}, {'text': 'skin lesion', 'type': 'Disease', 'start': 1310, 'end': 1321, 'mesh': 'D012871'}, {'text': ""Wilson's disease"", 'type': 'Disease', 'start': 1465, 'end': 1481, 'mesh': 'D006527'}, {'text': ""Wilson's disease"", 'type': 'Disease', 'start': 1559, 'end': 1575, 'mesh': 'D006527'}]"
+1434,17351238,A dramatic drop in blood pressure following prehospital GTN administration.,"A male in his sixties with no history of cardiac chest pain awoke with chest pain following an afternoon sleep. The patient did not self medicate. The patient's observations were within normal limits, he was administered oxygen via a face mask and glyceryl trinitrate (GTN). Several minutes after the GTN the patient experienced a sudden drop in blood pressure and heart rate, this was rectified by atropine sulphate and a fluid challenge. There was no further deterioration in the patient's condition during transport to hospital. There are very few documented case like this in the prehospital scientific literature. The cause appears to be the Bezold-Jarish reflex, stimulation of the ventricular walls which in turn decreases sympathetic outflow from the vasomotor centre. Prehospital care providers who are managing any patient with a syncopal episode that fails to recover within a reasonable time frame should consider the Bezold-Jarisch reflex as the cause and manage the patient accordingly.","[{'text': 'drop in blood pressure', 'type': 'Disease', 'start': 11, 'end': 33, 'mesh': 'D007022'}, {'text': 'GTN', 'type': 'Chemical', 'start': 56, 'end': 59, 'mesh': 'D005996'}, {'text': 'chest pain', 'type': 'Disease', 'start': 125, 'end': 135, 'mesh': 'D002637'}, {'text': 'chest pain', 'type': 'Disease', 'start': 147, 'end': 157, 'mesh': 'D002637'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 297, 'end': 303, 'mesh': 'D010100'}, {'text': 'glyceryl trinitrate', 'type': 'Chemical', 'start': 324, 'end': 343, 'mesh': 'D005996'}, {'text': 'GTN', 'type': 'Chemical', 'start': 345, 'end': 348, 'mesh': 'D005996'}, {'text': 'GTN', 'type': 'Chemical', 'start': 377, 'end': 380, 'mesh': 'D005996'}, {'text': 'drop in blood pressure', 'type': 'Disease', 'start': 414, 'end': 436, 'mesh': 'D007022'}, {'text': 'atropine sulphate', 'type': 'Chemical', 'start': 475, 'end': 492, 'mesh': 'D001285'}, {'text': 'syncopal episode', 'type': 'Disease', 'start': 916, 'end': 932, 'mesh': 'D013575'}]"
+1435,17356399,Acute encephalopathy and cerebral vasospasm after multiagent chemotherapy including PEG-asparaginase and intrathecal cytarabine for the treatment of acute lymphoblastic leukemia.,"A 7-year-old girl with an unusual reaction to induction chemotherapy for precursor B-cell acute lymphoblastic leukemia (ALL) is described. The patient developed acute encephalopathy evidenced by behavioral changes, aphasia, incontinence, visual hallucinations, and right-sided weakness with diffuse cerebral vasospasm on magnetic resonance angiography after the administration of intrathecal cytarabine. Vincristine, dexamethasone, and polyethylene glycol-asparaginase were also administered before the episode as part of induction therapy. Neurologic status returned to baseline within 10 days of the acute event, and magnetic resonance angiography findings returned to normal 4 months later.","[{'text': 'Acute encephalopathy', 'type': 'Disease', 'start': 0, 'end': 20, 'mesh': 'D020803'}, {'text': 'cerebral vasospasm', 'type': 'Disease', 'start': 25, 'end': 43, 'mesh': 'D020301'}, {'text': 'PEG-asparaginase', 'type': 'Chemical', 'start': 84, 'end': 100, 'mesh': 'C042705'}, {'text': 'cytarabine', 'type': 'Chemical', 'start': 117, 'end': 127, 'mesh': 'D003561'}, {'text': 'acute lymphoblastic leukemia', 'type': 'Disease', 'start': 149, 'end': 177, 'mesh': 'D054198'}, {'text': 'acute lymphoblastic leukemia', 'type': 'Disease', 'start': 269, 'end': 297, 'mesh': 'D054198'}, {'text': 'ALL', 'type': 'Disease', 'start': 299, 'end': 302, 'mesh': 'D054198'}, {'text': 'acute encephalopathy', 'type': 'Disease', 'start': 340, 'end': 360, 'mesh': 'D020803'}, {'text': 'aphasia', 'type': 'Disease', 'start': 394, 'end': 401, 'mesh': 'D001037'}, {'text': 'incontinence', 'type': 'Disease', 'start': 403, 'end': 415, 'mesh': 'D014549'}, {'text': 'visual hallucinations', 'type': 'Disease', 'start': 417, 'end': 438, 'mesh': 'D006212'}, {'text': 'weakness', 'type': 'Disease', 'start': 456, 'end': 464, 'mesh': 'D018908'}, {'text': 'cerebral vasospasm', 'type': 'Disease', 'start': 478, 'end': 496, 'mesh': 'D020301'}, {'text': 'cytarabine', 'type': 'Chemical', 'start': 571, 'end': 581, 'mesh': 'D003561'}, {'text': 'Vincristine', 'type': 'Chemical', 'start': 583, 'end': 594, 'mesh': 'D014750'}, {'text': 'dexamethasone', 'type': 'Chemical', 'start': 596, 'end': 609, 'mesh': 'D003907'}, {'text': 'polyethylene glycol-asparaginase', 'type': 'Chemical', 'start': 615, 'end': 647, 'mesh': 'C042705'}]"
+1436,17379047,"Comparison of valsartan/hydrochlorothiazide combination therapy at doses up to 320/25 mg versus monotherapy: a double-blind, placebo-controlled study followed by long-term combination therapy in hypertensive adults.","BACKGROUND: One third of patients treated for hypertension attain adequate blood pressure (BP) control, and multidrug regimens are often required. Given the lifelong nature of hypertension, there is a need to evaluate the long-term efficacy and tolerability of higher doses of combination anti-hypertensive therapies. OBJECTIVE: This study investigated the efficacy and tolerability of valsartan (VAL) or hydrochlorothiazide (HCTZ)-monotherapy and higher-dose combinations in patients with essential hypertension. METHODS: The first part of this study was an 8-week, multicenter, randomized, double-blind, placebo controlled, parallel-group trial. Patients with essential hypertension (mean sitting diastolic BP [MSDBP], > or =95 mm Hg and <110 mm Hg) were randomized to 1 of 8 treatment groups: VAL 160 or 320 mg; HCTZ 12.5 or 25 mg; VAL/HCTZ 160/12.5, 320/12.5, or 320/25 mg; or placebo. Mean changes in MSDBP and mean sitting systolic BP (MSSBP) were analyzed at the 8-week core study end point. VAL/HCTZ 320/12.5 and 320/25 mg were further investigated in a 54-week, open-label extension. Response was defined as MSDBP <90 mm Hg or a > or =10 mm Hg decrease compared to baseline. Control was defined as MSDBP <90 mm Hg compared with baseline. Tolerability was assessed by monitoring adverse events at randomization and all subsequent study visits and regular evaluation of hematology and blood chemistry. RESULTS: A total of 1346 patients were randomized into the 8-week core study (734 men, 612 women; 924 white, 291 black, 23 Asian, 108 other; mean age, 52.7 years; mean weight, 92.6 kg). All active treatments were associated with significantly reduced MSSBP and MSDBP during the core 8-week study, with each monotherapy significantly contributing to the overall effect of combination therapy (VAL and HCTZ, P < 0.001). Each combination was associated with significantly greater reductions in MSSBP and MSDBP compared with the monotherapies and placebo (all, P < 0.001). The mean reduction in MSSBP/MSDBP with VAL/HCTZ 320/25 mg was 24.7/16.6 mm Hg, compared with 5.9/7.0 mm Hg with placebo. The reduction in MSSBP was significantly greater with VAL/HCTZ 320/25 mg compared with VAL/HCTZ 160/12.5 mg (P < 0.002). Rates of response and BP control were significantly higher in the groups that received combination treatment compared with those that received monotherapy. The incidence of hypokalemia was lower with VAL/HCTZ combinations (1.8%-6.1%) than with HCTZ monotherapies (7.1%-13.3%). The majority of adverse events in the core study were of mild to moderate severity. The efficacy and tolerability of VAL/HCTZ combinations were maintained during the extension (797 patients). CONCLUSIONS: In this study population, combination therapies with VAL/HCTZ were associated with significantly greater BP reductions compared with either monotherapy, were well tolerated, and were associated with less hypokalemia than HCTZ alone.","[{'text': 'valsartan', 'type': 'Chemical', 'start': 14, 'end': 23, 'mesh': 'C081489'}, {'text': 'hydrochlorothiazide', 'type': 'Chemical', 'start': 24, 'end': 43, 'mesh': 'D006852'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 195, 'end': 207, 'mesh': 'D006973'}, {'text': 'hypertension', 'type': 'Disease', 'start': 262, 'end': 274, 'mesh': 'D006973'}, {'text': 'hypertension', 'type': 'Disease', 'start': 392, 'end': 404, 'mesh': 'D006973'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 510, 'end': 522, 'mesh': 'D006973'}, {'text': 'valsartan', 'type': 'Chemical', 'start': 602, 'end': 611, 'mesh': 'C081489'}, {'text': 'VAL', 'type': 'Chemical', 'start': 613, 'end': 616, 'mesh': 'C081489'}, {'text': 'hydrochlorothiazide', 'type': 'Chemical', 'start': 621, 'end': 640, 'mesh': 'D006852'}, {'text': 'HCTZ', 'type': 'Chemical', 'start': 642, 'end': 646, 'mesh': 'D006852'}, {'text': 'essential hypertension', 'type': 'Disease', 'start': 706, 'end': 728, 'mesh': 'C562386'}, {'text': 'essential hypertension', 'type': 'Disease', 'start': 878, 'end': 900, 'mesh': 'C562386'}, {'text': 'VAL', 'type': 'Chemical', 'start': 1012, 'end': 1015, 'mesh': 'C081489'}, {'text': 'HCTZ', 'type': 'Chemical', 'start': 1031, 'end': 1035, 'mesh': 'D006852'}, {'text': 'VAL', 'type': 'Chemical', 'start': 1051, 'end': 1054, 'mesh': 'C081489'}, {'text': 'HCTZ', 'type': 'Chemical', 'start': 1055, 'end': 1059, 'mesh': 'D006852'}, {'text': 'VAL', 'type': 'Chemical', 'start': 1215, 'end': 1218, 'mesh': 'C081489'}, {'text': 'HCTZ', 'type': 'Chemical', 'start': 1219, 'end': 1223, 'mesh': 'D006852'}, {'text': 'VAL', 'type': 'Chemical', 'start': 2017, 'end': 2020, 'mesh': 'C081489'}, {'text': 'HCTZ', 'type': 'Chemical', 'start': 2025, 'end': 2029, 'mesh': 'D006852'}, {'text': 'VAL', 'type': 'Chemical', 'start': 2233, 'end': 2236, 'mesh': 'C081489'}, {'text': 'HCTZ', 'type': 'Chemical', 'start': 2237, 'end': 2241, 'mesh': 'D006852'}, {'text': 'VAL', 'type': 'Chemical', 'start': 2369, 'end': 2372, 'mesh': 'C081489'}, {'text': 'HCTZ', 'type': 'Chemical', 'start': 2373, 'end': 2377, 'mesh': 'D006852'}, {'text': 'VAL', 'type': 'Chemical', 'start': 2402, 'end': 2405, 'mesh': 'C081489'}, {'text': 'HCTZ', 'type': 'Chemical', 'start': 2406, 'end': 2410, 'mesh': 'D006852'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 2609, 'end': 2620, 'mesh': 'D007008'}, {'text': 'VAL', 'type': 'Chemical', 'start': 2636, 'end': 2639, 'mesh': 'C081489'}, {'text': 'HCTZ', 'type': 'Chemical', 'start': 2640, 'end': 2644, 'mesh': 'D006852'}, {'text': 'HCTZ', 'type': 'Chemical', 'start': 2680, 'end': 2684, 'mesh': 'D006852'}, {'text': 'VAL', 'type': 'Chemical', 'start': 2830, 'end': 2833, 'mesh': 'C081489'}, {'text': 'HCTZ', 'type': 'Chemical', 'start': 2834, 'end': 2838, 'mesh': 'D006852'}, {'text': 'VAL', 'type': 'Chemical', 'start': 2971, 'end': 2974, 'mesh': 'C081489'}, {'text': 'HCTZ', 'type': 'Chemical', 'start': 2975, 'end': 2979, 'mesh': 'D006852'}, {'text': 'hypokalemia', 'type': 'Disease', 'start': 3122, 'end': 3133, 'mesh': 'D007008'}, {'text': 'HCTZ', 'type': 'Chemical', 'start': 3139, 'end': 3143, 'mesh': 'D006852'}]"
+1437,17384765,"Succimer chelation improves learning, attention, and arousal regulation in lead-exposed rats but produces lasting cognitive impairment in the absence of lead exposure.","BACKGROUND: There is growing pressure for clinicians to prescribe chelation therapy at only slightly elevated blood lead levels. However, very few studies have evaluated whether chelation improves cognitive outcomes in Pb-exposed children, or whether these agents have adverse effects that may affect brain development in the absence of Pb exposure. OBJECTIVES: The present study was designed to answer these questions, using a rodent model of early childhood Pb exposure and treatment with succimer, a widely used chelating agent for the treatment of Pb poisoning. RESULTS: Pb exposure produced lasting impairments in learning, attention, inhibitory control, and arousal regulation, paralleling the areas of dysfunction seen in Pb-exposed children. Succimer treatment of the Pb-exposed rats significantly improved learning, attention, and arousal regulation, although the efficacy of the treatment varied as a function of the Pb exposure level and the specific functional deficit. In contrast, succimer treatment of rats not previously exposed to Pb produced lasting and pervasive cognitive and affective dysfunction comparable in magnitude to that produced by the higher Pb exposure regimen. CONCLUSIONS: These are the first data, to our knowledge, to show that treatment with any chelating agent can alleviate cognitive deficits due to Pb exposure. These findings suggest that it may be possible to identify a succimer treatment protocol that improves cognitive outcomes in Pb-exposed children. However, they also suggest that succimer treatment should be strongly discouraged for children who do not have elevated tissue levels of Pb or other heavy metals.","[{'text': 'Succimer', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D004113'}, {'text': 'lead', 'type': 'Chemical', 'start': 75, 'end': 79, 'mesh': 'D007854'}, {'text': 'cognitive impairment', 'type': 'Disease', 'start': 114, 'end': 134, 'mesh': 'D003072'}, {'text': 'lead', 'type': 'Chemical', 'start': 153, 'end': 157, 'mesh': 'D007854'}, {'text': 'lead', 'type': 'Chemical', 'start': 284, 'end': 288, 'mesh': 'D007854'}, {'text': 'Pb', 'type': 'Chemical', 'start': 387, 'end': 389, 'mesh': 'D007854'}, {'text': 'Pb', 'type': 'Chemical', 'start': 505, 'end': 507, 'mesh': 'D007854'}, {'text': 'Pb', 'type': 'Chemical', 'start': 628, 'end': 630, 'mesh': 'D007854'}, {'text': 'succimer', 'type': 'Chemical', 'start': 659, 'end': 667, 'mesh': 'D004113'}, {'text': 'Pb poisoning', 'type': 'Disease', 'start': 720, 'end': 732, 'mesh': 'D007855'}, {'text': 'Pb', 'type': 'Chemical', 'start': 743, 'end': 745, 'mesh': 'D007854'}, {'text': 'Pb', 'type': 'Chemical', 'start': 897, 'end': 899, 'mesh': 'D007854'}, {'text': 'Succimer', 'type': 'Chemical', 'start': 918, 'end': 926, 'mesh': 'D004113'}, {'text': 'Pb', 'type': 'Chemical', 'start': 944, 'end': 946, 'mesh': 'D007854'}, {'text': 'Pb', 'type': 'Chemical', 'start': 1095, 'end': 1097, 'mesh': 'D007854'}, {'text': 'succimer', 'type': 'Chemical', 'start': 1163, 'end': 1171, 'mesh': 'D004113'}, {'text': 'Pb', 'type': 'Chemical', 'start': 1216, 'end': 1218, 'mesh': 'D007854'}, {'text': 'Pb', 'type': 'Chemical', 'start': 1341, 'end': 1343, 'mesh': 'D007854'}, {'text': 'cognitive deficits', 'type': 'Disease', 'start': 1481, 'end': 1499, 'mesh': 'D003072'}, {'text': 'Pb', 'type': 'Chemical', 'start': 1507, 'end': 1509, 'mesh': 'D007854'}, {'text': 'succimer', 'type': 'Chemical', 'start': 1581, 'end': 1589, 'mesh': 'D004113'}, {'text': 'Pb', 'type': 'Chemical', 'start': 1645, 'end': 1647, 'mesh': 'D007854'}, {'text': 'succimer', 'type': 'Chemical', 'start': 1698, 'end': 1706, 'mesh': 'D004113'}, {'text': 'Pb', 'type': 'Chemical', 'start': 1803, 'end': 1805, 'mesh': 'D007854'}]"
+1438,17445520,Caffeine challenge test in panic disorder and depression with panic attacks.,"Our aim was to observe if patients with panic disorder (PD) and patients with major depression with panic attacks (MDP) (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) respond in a similar way to the induction of panic attacks by an oral caffeine challenge test. We randomly selected 29 patients with PD, 27 with MDP, 25 with major depression without panic attacks (MD), and 28 healthy volunteers. The patients had no psychotropic drug for at least a 4-week period. In a randomized double-blind experiment performed in 2 occasions 7 days apart, 480 mg caffeine and a caffeine-free (placebo) solution were administered in a coffee form and anxiety scales were applied before and after each test. A total of 58.6% (n = 17) of patients with PD, 44.4% (n = 12) of patients with MDP, 12.0% (n = 3) of patients with MD, and 7.1% (n= 2) of control subjects had a panic attack after the 480-mg caffeine challenge test (chi(2)(3) = 16.22, P = .001). The patients with PD and MDP were more sensitive to caffeine than were patients with MD and healthy volunteers. No panic attack was observed after the caffeine-free solution intake. The patients with MD had a lower heart rate response to the test than all the other groups (2-way analysis of variance, group by time interaction with Greenhouse-Geisser correction: F(3,762) = 2.85, P = .026). Our data suggest that there is an association between panic attacks, no matter if associated with PD or MDP, and hyperreactivity to an oral caffeine challenge test.","[{'text': 'Caffeine', 'type': 'Chemical', 'start': 0, 'end': 8, 'mesh': 'D002110'}, {'text': 'panic disorder', 'type': 'Disease', 'start': 27, 'end': 41, 'mesh': 'D016584'}, {'text': 'depression', 'type': 'Disease', 'start': 46, 'end': 56, 'mesh': 'D003866'}, {'text': 'panic attacks', 'type': 'Disease', 'start': 62, 'end': 75, 'mesh': 'D016584'}, {'text': 'panic disorder', 'type': 'Disease', 'start': 117, 'end': 131, 'mesh': 'D016584'}, {'text': 'PD', 'type': 'Disease', 'start': 133, 'end': 135, 'mesh': 'D016584'}, {'text': 'major depression', 'type': 'Disease', 'start': 155, 'end': 171, 'mesh': 'D003865'}, {'text': 'panic attacks', 'type': 'Disease', 'start': 177, 'end': 190, 'mesh': 'D016584'}, {'text': 'MDP', 'type': 'Disease', 'start': 192, 'end': 195, 'mesh': 'D003865|D016584'}, {'text': 'Mental Disorders', 'type': 'Disease', 'start': 235, 'end': 251, 'mesh': 'D001523'}, {'text': 'panic attacks', 'type': 'Disease', 'start': 323, 'end': 336, 'mesh': 'D016584'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 348, 'end': 356, 'mesh': 'D002110'}, {'text': 'PD', 'type': 'Disease', 'start': 411, 'end': 413, 'mesh': 'D016584'}, {'text': 'MDP', 'type': 'Disease', 'start': 423, 'end': 426, 'mesh': 'D003865|D016584'}, {'text': 'major depression', 'type': 'Disease', 'start': 436, 'end': 452, 'mesh': 'D003865'}, {'text': 'panic attacks', 'type': 'Disease', 'start': 461, 'end': 474, 'mesh': 'D016584'}, {'text': 'MD', 'type': 'Disease', 'start': 476, 'end': 478, 'mesh': 'D003865'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 662, 'end': 670, 'mesh': 'D002110'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 677, 'end': 685, 'mesh': 'D002110'}, {'text': 'anxiety', 'type': 'Disease', 'start': 749, 'end': 756, 'mesh': 'D001008'}, {'text': 'PD', 'type': 'Disease', 'start': 848, 'end': 850, 'mesh': 'D016584'}, {'text': 'MDP', 'type': 'Disease', 'start': 884, 'end': 887, 'mesh': 'D003865|D016584'}, {'text': 'MD', 'type': 'Disease', 'start': 920, 'end': 922, 'mesh': 'D003865'}, {'text': 'panic attack', 'type': 'Disease', 'start': 966, 'end': 978, 'mesh': 'D016584'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 996, 'end': 1004, 'mesh': 'D002110'}, {'text': 'PD', 'type': 'Disease', 'start': 1069, 'end': 1071, 'mesh': 'D016584'}, {'text': 'MDP', 'type': 'Disease', 'start': 1076, 'end': 1079, 'mesh': 'D003865|D016584'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1103, 'end': 1111, 'mesh': 'D002110'}, {'text': 'MD', 'type': 'Disease', 'start': 1136, 'end': 1138, 'mesh': 'D003865'}, {'text': 'panic attack', 'type': 'Disease', 'start': 1166, 'end': 1178, 'mesh': 'D016584'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1202, 'end': 1210, 'mesh': 'D002110'}, {'text': 'MD', 'type': 'Disease', 'start': 1251, 'end': 1253, 'mesh': 'D003865'}, {'text': 'panic attacks', 'type': 'Disease', 'start': 1497, 'end': 1510, 'mesh': 'D016584'}, {'text': 'PD', 'type': 'Disease', 'start': 1541, 'end': 1543, 'mesh': 'D016584'}, {'text': 'MDP', 'type': 'Disease', 'start': 1547, 'end': 1550, 'mesh': 'D003865|D016584'}, {'text': 'caffeine', 'type': 'Chemical', 'start': 1583, 'end': 1591, 'mesh': 'D002110'}]"
+1439,17484470,Mitral annuloplasty as a ventricular restoration method for the failing left ventricle: a pilot study.,"BACKGROUND AND AIM OF THE STUDY: Undersized mitral annuloplasty (MAP) is effective in patients with dilated cardiomyopathy and functional mitral regurgitation (MR) since, as well as addressing the MR, the MAP may also reshape the dilated left ventricular (LV) base. However, the direct benefits of this possible reshaping on LV function in the absence of underlying MR remain incompletely understood. The study aim was to identify these benefits in a canine model of acute heart failure. METHODS: Six dogs underwent MAP with a prosthetic band on the posterior mitral annulus, using four mattress sutures. The sutures were passed individually through four tourniquets and exteriorized untied via the left atriotomy. Sonomicrometry crystals were implanted around the mitral annulus and left ventricle to measure geometry and regional function. Acute heart failure was induced by propranolol and volume loading after weaning from cardiopulmonary bypass; an absence of MR was confirmed by echocardiography. MAP was accomplished by cinching the tourniquets. Data were acquired at baseline, after induction of acute heart failure, and after MAP. RESULTS: MAP decreased mitral annular dimensions in both commissure-commissure and septal-lateral directions. Concomitantly, the diastolic diameter of the LV base and LV sphericity decreased (i.e., improved) from 37.4 +/- 9.3 to 35.9 +/- 10 mm (p = 0.063), and from 67.9 +/- 18.6% to 65.3 +/- 18.9% (p = 0.016), respectively. Decreases were evident in both LV end-diastolic pressure (from 17 +/- 7 to 15 +/- 6 mmHg, p = 0.0480 and Tau (from 48 +/- 8 to 45 +/- 8 ms, p <0.01), while fractional shortening at the LV base increased from 7.7 +/- 4.5% to 9.4 +/- 4.5% (p = 0.045). After MAP, increases were identified in both cardiac output (from 1.54 +/- 0.57 to 1.65 +/- 0.57 1/min) and Emax (from 1.86 +/- 0.9 to 2.41 +/- 1.31 mmHg/ml). CONCLUSION: The data acquired suggest that isolated MAP may have certain benefits on LV dimension/function in acute heart failure, even in the absence of MR. However, further investigations are warranted in a model of chronic heart failure.","[{'text': 'failing left ventricle', 'type': 'Disease', 'start': 64, 'end': 86, 'mesh': 'D006333'}, {'text': 'dilated cardiomyopathy', 'type': 'Disease', 'start': 203, 'end': 225, 'mesh': 'D002311'}, {'text': 'mitral regurgitation', 'type': 'Disease', 'start': 241, 'end': 261, 'mesh': 'D008944'}, {'text': 'MR', 'type': 'Disease', 'start': 263, 'end': 265, 'mesh': 'D008944'}, {'text': 'MR', 'type': 'Disease', 'start': 300, 'end': 302, 'mesh': 'D008944'}, {'text': 'MR', 'type': 'Disease', 'start': 469, 'end': 471, 'mesh': 'D008944'}, {'text': 'heart failure', 'type': 'Disease', 'start': 576, 'end': 589, 'mesh': 'D006333'}, {'text': 'heart failure', 'type': 'Disease', 'start': 951, 'end': 964, 'mesh': 'D006333'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 980, 'end': 991, 'mesh': 'D011433'}, {'text': 'MR', 'type': 'Disease', 'start': 1068, 'end': 1070, 'mesh': 'D008944'}, {'text': 'heart failure', 'type': 'Disease', 'start': 1213, 'end': 1226, 'mesh': 'D006333'}, {'text': 'heart failure', 'type': 'Disease', 'start': 2094, 'end': 2107, 'mesh': 'D006333'}, {'text': 'MR', 'type': 'Disease', 'start': 2132, 'end': 2134, 'mesh': 'D008944'}, {'text': 'heart failure', 'type': 'Disease', 'start': 2204, 'end': 2217, 'mesh': 'D006333'}]"
+1440,17496739,Piperacillin/tazobactam-induced seizure rapidly reversed by high flux hemodialysis in a patient on peritoneal dialysis.,"Despite popular use of piperacillin, the dire neurotoxicity associated with piperacillin still goes unrecognized, leading to a delay in appropriate management. We report a 57-year-old woman with end-stage renal disease receiving continuous ambulatory peritoneal dialysis (CAPD), who developed slurred speech, tremor, bizarre behavior, progressive mental confusion, and 2 episodes of generalized tonic-clonic seizure (GTCS) after 5 doses of piperacillin/tazobactam (2 g/250 mg) were given for bronchiectasis with secondary infection. The laboratory data revealed normal plasma electrolyte and ammonia levels but leukocytosis. Neurologic examinations showed dysarthria and bilateral Babinski sign. Computed tomography of brain and electroencephalogram were unremarkable. Despite the use of antiepileptic agents, another GTCS episode recurred after the sixth dose of piperacillin/tazobactam. Brain magnetic resonance imaging did not demonstrate acute infarction and organic brain lesions. Initiation of high-flux hemodialysis rapidly reversed the neurologic symptoms within 4 hours. Piperacillin-induced encephalopathy should be considered in any uremic patients with unexplained neurological manifestations. CAPD is inefficient in removing piperacillin, whereas hemodialysis can rapidly terminate the piperacillin-induced encephalopathy.","[{'text': 'Piperacillin/tazobactam', 'type': 'Chemical', 'start': 0, 'end': 23, 'mesh': 'C085143'}, {'text': 'seizure', 'type': 'Disease', 'start': 32, 'end': 39, 'mesh': 'D012640'}, {'text': 'piperacillin', 'type': 'Chemical', 'start': 143, 'end': 155, 'mesh': 'D010878'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 166, 'end': 179, 'mesh': 'D020258'}, {'text': 'piperacillin', 'type': 'Chemical', 'start': 196, 'end': 208, 'mesh': 'D010878'}, {'text': 'end-stage renal disease', 'type': 'Disease', 'start': 315, 'end': 338, 'mesh': 'D007676'}, {'text': 'tremor', 'type': 'Disease', 'start': 429, 'end': 435, 'mesh': 'D014202'}, {'text': 'confusion', 'type': 'Disease', 'start': 474, 'end': 483, 'mesh': 'D003221'}, {'text': 'tonic-clonic seizure', 'type': 'Disease', 'start': 515, 'end': 535, 'mesh': 'D004830'}, {'text': 'GTCS', 'type': 'Disease', 'start': 537, 'end': 541, 'mesh': 'D004830'}, {'text': 'piperacillin/tazobactam', 'type': 'Chemical', 'start': 560, 'end': 583, 'mesh': 'C085143'}, {'text': 'bronchiectasis', 'type': 'Disease', 'start': 612, 'end': 626, 'mesh': 'D001987'}, {'text': 'secondary infection', 'type': 'Disease', 'start': 632, 'end': 651, 'mesh': 'D060085'}, {'text': 'ammonia', 'type': 'Chemical', 'start': 712, 'end': 719, 'mesh': 'D000641'}, {'text': 'leukocytosis', 'type': 'Disease', 'start': 731, 'end': 743, 'mesh': 'D007964'}, {'text': 'dysarthria', 'type': 'Disease', 'start': 776, 'end': 786, 'mesh': 'D004401'}, {'text': 'GTCS', 'type': 'Disease', 'start': 938, 'end': 942, 'mesh': 'D004830'}, {'text': 'piperacillin/tazobactam', 'type': 'Chemical', 'start': 984, 'end': 1007, 'mesh': 'C085143'}, {'text': 'infarction', 'type': 'Disease', 'start': 1068, 'end': 1078, 'mesh': 'D007238'}, {'text': 'organic brain lesions', 'type': 'Disease', 'start': 1083, 'end': 1104, 'mesh': '-1'}, {'text': 'Piperacillin', 'type': 'Chemical', 'start': 1200, 'end': 1212, 'mesh': 'D010878'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 1221, 'end': 1235, 'mesh': 'D001927'}, {'text': 'uremic', 'type': 'Disease', 'start': 1264, 'end': 1270, 'mesh': 'D006463'}, {'text': 'piperacillin', 'type': 'Chemical', 'start': 1358, 'end': 1370, 'mesh': 'D010878'}, {'text': 'piperacillin', 'type': 'Chemical', 'start': 1419, 'end': 1431, 'mesh': 'D010878'}, {'text': 'encephalopathy', 'type': 'Disease', 'start': 1440, 'end': 1454, 'mesh': 'D001927'}]"
+1441,17543491,Frequency of transient ipsilateral vocal cord paralysis in patients undergoing carotid endarterectomy under local anesthesia.,"BACKGROUND: Especially because of improvements in clinical neurologic monitoring, carotid endarterectomy done under local anesthesia has become the technique of choice in several centers. Temporary ipsilateral vocal nerve palsies due to local anesthetics have been described, however. Such complications are most important in situations where there is a pre-existing contralateral paralysis. We therefore examined the effect of local anesthesia on vocal cord function to better understand its possible consequences. METHODS: This prospective study included 28 patients undergoing carotid endarterectomy under local anesthesia. Vocal cord function was evaluated before, during, and after surgery (postoperative day 1) using flexible laryngoscopy. Anesthesia was performed by injecting 20 to 40 mL of a mixture of long-acting (ropivacaine) and short-acting (prilocaine) anesthetic. RESULTS: All patients had normal vocal cord function preoperatively. Twelve patients (43%) were found to have intraoperative ipsilateral vocal cord paralysis. It resolved in all cases < or =24 hours. There were no significant differences in operating time or volume or frequency of anesthetic administration in patients with temporary vocal cord paralysis compared with those without. CONCLUSION: Local anesthesia led to temporary ipsilateral vocal cord paralysis in almost half of these patients. Because pre-existing paralysis is of a relevant frequency (up to 3%), a preoperative evaluation of vocal cord function before carotid endarterectomy under local anesthesia is recommended to avoid intraoperative bilateral paralysis. In patients with preoperative contralateral vocal cord paralysis, surgery under general anesthesia should be considered.","[{'text': 'vocal cord paralysis', 'type': 'Disease', 'start': 35, 'end': 55, 'mesh': 'D014826'}, {'text': 'vocal nerve palsies', 'type': 'Disease', 'start': 336, 'end': 355, 'mesh': 'D014826'}, {'text': 'paralysis', 'type': 'Disease', 'start': 507, 'end': 516, 'mesh': 'D010243'}, {'text': 'ropivacaine', 'type': 'Chemical', 'start': 951, 'end': 962, 'mesh': 'C037663'}, {'text': 'prilocaine', 'type': 'Chemical', 'start': 982, 'end': 992, 'mesh': 'D011318'}, {'text': 'vocal cord paralysis', 'type': 'Disease', 'start': 1143, 'end': 1163, 'mesh': 'D014826'}, {'text': 'vocal cord paralysis', 'type': 'Disease', 'start': 1341, 'end': 1361, 'mesh': 'D014826'}, {'text': 'vocal cord paralysis', 'type': 'Disease', 'start': 1449, 'end': 1469, 'mesh': 'D014826'}, {'text': 'paralysis', 'type': 'Disease', 'start': 1525, 'end': 1534, 'mesh': 'D010243'}, {'text': 'paralysis', 'type': 'Disease', 'start': 1725, 'end': 1734, 'mesh': 'D010243'}, {'text': 'vocal cord paralysis', 'type': 'Disease', 'start': 1780, 'end': 1800, 'mesh': 'D014826'}]"
+1442,17572393,Neuroprotective effects of melatonin upon the offspring cerebellar cortex in the rat model of BCNU-induced cortical dysplasia.,"Cortical dysplasia is a malformation characterized by defects in proliferation, migration and maturation. This study was designed to evaluate the alterations in offspring rat cerebellum induced by maternal exposure to carmustine-[1,3-bis (2-chloroethyl)-1-nitrosoure] (BCNU) and to investigate the effects of exogenous melatonin upon cerebellar BCNU-induced cortical dysplasia, using histological and biochemical analyses. Pregnant Wistar rats were assigned to five groups: intact-control, saline-control, melatonin-treated, BCNU-exposed and BCNU-exposed plus melatonin. Rats were exposed to BCNU on embryonic day 15 and melatonin was given until delivery. Immuno/histochemistry and electron microscopy were carried out on the offspring cerebellum, and levels of malondialdehyde and superoxide dismutase were determined. Histopathologically, typical findings were observed in the cerebella from the control groups, but the findings consistent with early embryonic development were noted in BCNU-exposed cortical dysplasia group. There was a marked increase in the number of TUNEL positive cells and nestin positive cells in BCNU-exposed group, but a decreased immunoreactivity to glial fibrillary acidic protein, synaptophysin and transforming growth factor beta1 was observed, indicating a delayed maturation, and melatonin significantly reversed these changes. Malondialdehyde level in BCNU-exposed group was higher than those in control groups and melatonin decreased malondialdehyde levels in BCNU group (P<0.01), while there were no significant differences in the superoxide dismutase levels between these groups. These data suggest that exposure of animals to BCNU during pregnancy leads to delayed maturation of offspring cerebellum and melatonin protects the cerebellum against the effects of BCNU.","[{'text': 'melatonin', 'type': 'Chemical', 'start': 27, 'end': 36, 'mesh': 'D008550'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 94, 'end': 98, 'mesh': 'D002330'}, {'text': 'cortical dysplasia', 'type': 'Disease', 'start': 107, 'end': 125, 'mesh': 'D054220'}, {'text': 'Cortical dysplasia', 'type': 'Disease', 'start': 127, 'end': 145, 'mesh': 'D054220'}, {'text': 'carmustine', 'type': 'Chemical', 'start': 345, 'end': 355, 'mesh': 'D002330'}, {'text': '1,3-bis (2-chloroethyl)-1-nitrosoure', 'type': 'Chemical', 'start': 357, 'end': 393, 'mesh': 'D002330'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 396, 'end': 400, 'mesh': 'D002330'}, {'text': 'melatonin', 'type': 'Chemical', 'start': 446, 'end': 455, 'mesh': 'D008550'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 472, 'end': 476, 'mesh': 'D002330'}, {'text': 'cortical dysplasia', 'type': 'Disease', 'start': 485, 'end': 503, 'mesh': 'D054220'}, {'text': 'melatonin', 'type': 'Chemical', 'start': 633, 'end': 642, 'mesh': 'D008550'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 652, 'end': 656, 'mesh': 'D002330'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 669, 'end': 673, 'mesh': 'D002330'}, {'text': 'melatonin', 'type': 'Chemical', 'start': 687, 'end': 696, 'mesh': 'D008550'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 719, 'end': 723, 'mesh': 'D002330'}, {'text': 'melatonin', 'type': 'Chemical', 'start': 748, 'end': 757, 'mesh': 'D008550'}, {'text': 'malondialdehyde', 'type': 'Chemical', 'start': 890, 'end': 905, 'mesh': 'D008315'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 910, 'end': 920, 'mesh': 'D013481'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 1117, 'end': 1121, 'mesh': 'D002330'}, {'text': 'cortical dysplasia', 'type': 'Disease', 'start': 1130, 'end': 1148, 'mesh': 'D054220'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 1251, 'end': 1255, 'mesh': 'D002330'}, {'text': 'melatonin', 'type': 'Chemical', 'start': 1442, 'end': 1451, 'mesh': 'D008550'}, {'text': 'Malondialdehyde', 'type': 'Chemical', 'start': 1490, 'end': 1505, 'mesh': 'D008315'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 1515, 'end': 1519, 'mesh': 'D002330'}, {'text': 'melatonin', 'type': 'Chemical', 'start': 1578, 'end': 1587, 'mesh': 'D008550'}, {'text': 'malondialdehyde', 'type': 'Chemical', 'start': 1598, 'end': 1613, 'mesh': 'D008315'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 1624, 'end': 1628, 'mesh': 'D002330'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 1696, 'end': 1706, 'mesh': 'D013481'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 1793, 'end': 1797, 'mesh': 'D002330'}, {'text': 'melatonin', 'type': 'Chemical', 'start': 1871, 'end': 1880, 'mesh': 'D008550'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 1928, 'end': 1932, 'mesh': 'D002330'}]"
+1443,17828434,Myo-inositol-1-phosphate (MIP) synthase inhibition: in-vivo study in rats.,Lithium and valproate are the prototypic mood stabilizers and have diverse structures and targets. Both drugs influence inositol metabolism. Lithium inhibits IMPase and valproate inhibits MIP synthase. This study shows that MIP synthase inhibition does not replicate or augment the effects of lithium in the inositol sensitive pilocarpine-induced seizures model. This lack of effects may stem from the low contribution of de-novo synthesis to cellular inositol supply or to the inhibition of the de-novo synthesis by lithium itself.,"[{'text': 'Myo-inositol-1-phosphate', 'type': 'Chemical', 'start': 0, 'end': 24, 'mesh': 'C002647'}, {'text': 'MIP', 'type': 'Chemical', 'start': 26, 'end': 29, 'mesh': 'C002647'}, {'text': 'Lithium', 'type': 'Chemical', 'start': 75, 'end': 82, 'mesh': 'D008094'}, {'text': 'valproate', 'type': 'Chemical', 'start': 87, 'end': 96, 'mesh': 'D014635'}, {'text': 'inositol', 'type': 'Chemical', 'start': 195, 'end': 203, 'mesh': 'D007294'}, {'text': 'Lithium', 'type': 'Chemical', 'start': 216, 'end': 223, 'mesh': 'D008094'}, {'text': 'valproate', 'type': 'Chemical', 'start': 244, 'end': 253, 'mesh': 'D014635'}, {'text': 'MIP', 'type': 'Chemical', 'start': 263, 'end': 266, 'mesh': 'C002647'}, {'text': 'MIP', 'type': 'Chemical', 'start': 299, 'end': 302, 'mesh': 'C002647'}, {'text': 'lithium', 'type': 'Chemical', 'start': 368, 'end': 375, 'mesh': 'D008094'}, {'text': 'inositol', 'type': 'Chemical', 'start': 383, 'end': 391, 'mesh': 'D007294'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 402, 'end': 413, 'mesh': 'D010862'}, {'text': 'seizures', 'type': 'Disease', 'start': 422, 'end': 430, 'mesh': 'D012640'}, {'text': 'inositol', 'type': 'Chemical', 'start': 527, 'end': 535, 'mesh': 'D007294'}, {'text': 'lithium', 'type': 'Chemical', 'start': 592, 'end': 599, 'mesh': 'D008094'}]"
+1444,17879100,Non-steroidal anti-inflammatory drugs-associated acute interstitial nephritis with granular tubular basement membrane deposits.,"Acute tubulo-interstitial nephritis (ATIN) is an important cause of acute renal failure resulting from a variety of insults, including immune complex-mediated tubulo-interstitial injury, but drugs such as non-steroidal anti-inflammatory drugs (NSAIDs) are a far more frequent cause. Overall, as an entity, ATIN remains under-diagnosed, as symptoms resolve spontaneously if the medication is stopped. We report on a 14-year-old boy who developed acute renal failure 2 weeks after aortic valve surgery. He was put on aspirin following surgery and took ibuprofen for fever for nearly a week prior to presentation. He then presented to the emergency department feeling quite ill and was found to have a blood urea nitrogen (BUN) concentration of of 147 mg/dl, creatinine of 15.3 mg/dl and serum potassium of 8.7 mEq/l. Dialysis was immediately initiated. A kidney biopsy showed inflammatory infiltrate consistent with ATIN. However, in the tubular basement membrane (TBM), very intense granular deposits of polyclonal IgG and C3 were noted. He needed dialysis for 2 weeks and was treated successfully with steroids for 6 months. His renal recovery and disappearance of proteinuria took a year. In conclusion, this is a first report of NSAIDs-associated ATIN, showing deposits of granular immune complex present only in the TBM and not in the glomeruli.","[{'text': 'interstitial nephritis', 'type': 'Disease', 'start': 55, 'end': 77, 'mesh': 'D009395'}, {'text': 'Acute tubulo-interstitial nephritis', 'type': 'Disease', 'start': 128, 'end': 163, 'mesh': 'C564356'}, {'text': 'ATIN', 'type': 'Disease', 'start': 165, 'end': 169, 'mesh': 'C564356'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 196, 'end': 215, 'mesh': 'D058186'}, {'text': 'tubulo-interstitial injury', 'type': 'Disease', 'start': 287, 'end': 313, 'mesh': 'D009395'}, {'text': 'ATIN', 'type': 'Disease', 'start': 434, 'end': 438, 'mesh': 'C564356'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 573, 'end': 592, 'mesh': 'D058186'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 643, 'end': 650, 'mesh': 'D001241'}, {'text': 'ibuprofen', 'type': 'Chemical', 'start': 678, 'end': 687, 'mesh': 'D007052'}, {'text': 'fever', 'type': 'Disease', 'start': 692, 'end': 697, 'mesh': 'D005334'}, {'text': 'blood urea nitrogen', 'type': 'Chemical', 'start': 827, 'end': 846, 'mesh': 'D001806'}, {'text': 'BUN', 'type': 'Chemical', 'start': 848, 'end': 851, 'mesh': 'D001806'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 884, 'end': 894, 'mesh': 'D003404'}, {'text': 'potassium', 'type': 'Chemical', 'start': 919, 'end': 928, 'mesh': 'D011188'}, {'text': 'ATIN', 'type': 'Disease', 'start': 1042, 'end': 1046, 'mesh': 'C564356'}, {'text': 'steroids', 'type': 'Chemical', 'start': 1230, 'end': 1238, 'mesh': 'D013256'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1293, 'end': 1304, 'mesh': 'D011507'}, {'text': 'ATIN', 'type': 'Disease', 'start': 1377, 'end': 1381, 'mesh': 'C564356'}]"
+1445,17879217,Rifampicin-associated segmental necrotizing glomerulonephritis in staphylococcal endocarditis.,"Segmental necrotising glomerulonephritis has been reported as complication of rifampicin therapy in patients receiving treatment for tuberculosis. Changing epidemiology of infections such as infective endocarditis (IE) has led to an increase in the use of rifampicin for Staphylococcal infections. We describe a case of a patient with Staphylococcal IE who developed acute renal failure secondary to a segmental necrotising glomerulonephritis while being treated with rifampicin, and review the literature regarding this complication of rifampicin therapy.","[{'text': 'Rifampicin', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D012293'}, {'text': 'glomerulonephritis', 'type': 'Disease', 'start': 44, 'end': 62, 'mesh': 'D005921'}, {'text': 'glomerulonephritis', 'type': 'Disease', 'start': 117, 'end': 135, 'mesh': 'D005921'}, {'text': 'rifampicin', 'type': 'Chemical', 'start': 173, 'end': 183, 'mesh': 'D012293'}, {'text': 'tuberculosis', 'type': 'Disease', 'start': 228, 'end': 240, 'mesh': 'D014376'}, {'text': 'infections', 'type': 'Disease', 'start': 267, 'end': 277, 'mesh': 'D007239'}, {'text': 'infective endocarditis', 'type': 'Disease', 'start': 286, 'end': 308, 'mesh': 'D004696'}, {'text': 'IE', 'type': 'Disease', 'start': 310, 'end': 312, 'mesh': 'D004696'}, {'text': 'rifampicin', 'type': 'Chemical', 'start': 351, 'end': 361, 'mesh': 'D012293'}, {'text': 'Staphylococcal infections', 'type': 'Disease', 'start': 366, 'end': 391, 'mesh': 'D013203'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 462, 'end': 481, 'mesh': 'D058186'}, {'text': 'glomerulonephritis', 'type': 'Disease', 'start': 519, 'end': 537, 'mesh': 'D005921'}, {'text': 'rifampicin', 'type': 'Chemical', 'start': 563, 'end': 573, 'mesh': 'D012293'}, {'text': 'rifampicin', 'type': 'Chemical', 'start': 632, 'end': 642, 'mesh': 'D012293'}]"
+1446,17954033,Rate of YMDD motif mutants in lamivudine-untreated Iranian patients with chronic hepatitis B virus infection.,"BACKGROUND: Lamivudine is used for the treatment of chronic hepatitis B patients. Recent studies show that the YMDD motif mutants (resistant hepatitis B virus) occur as natural genome variability in lamivudine-untreated chronic hepatitis B patients. In this study we aimed to determine the rate of YMDD motif mutants in lamivudine-untreated chronic hepatitis B patients in Iran. PATIENTS AND METHODS: A total of 77 chronic hepatitis B patients who had not been treated with lamivudine were included in the study. Serum samples from patients were tested by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for detection of YMDD motif mutants. All patients were also tested for liver enzymes, anti-HCV, HBeAg, and anti-HBe. RESULTS: Of the 77 patients enrolled in the study, 73% were male and 27% were female. Mean ALT and AST levels were 124.4+/-73.4 and 103.1+/-81 IU/l, respectively. HBeAg was positive in 40% and anti-HBe in 60% of the patients. Anti-HCV was negative in all of them. YMDD motif mutants were not detected in any of the patients despite the liver enzyme levels and the presence of HBeAg or anti-HBe. CONCLUSION: Although the natural occurrence of YMDD motif mutants in lamivudine-untreated patients with chronic hepatitis B has been reported, these mutants were not detected in Iranian lamivudine-untreated chronic hepatitis B patients.","[{'text': 'lamivudine', 'type': 'Chemical', 'start': 30, 'end': 40, 'mesh': 'D019259'}, {'text': 'chronic hepatitis B virus infection', 'type': 'Disease', 'start': 73, 'end': 108, 'mesh': 'D019694'}, {'text': 'Lamivudine', 'type': 'Chemical', 'start': 122, 'end': 132, 'mesh': 'D019259'}, {'text': 'chronic hepatitis B', 'type': 'Disease', 'start': 162, 'end': 181, 'mesh': 'D019694'}, {'text': 'hepatitis B', 'type': 'Disease', 'start': 251, 'end': 262, 'mesh': 'D006509'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 309, 'end': 319, 'mesh': 'D019259'}, {'text': 'chronic hepatitis B', 'type': 'Disease', 'start': 330, 'end': 349, 'mesh': 'D019694'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 430, 'end': 440, 'mesh': 'D019259'}, {'text': 'chronic hepatitis B', 'type': 'Disease', 'start': 451, 'end': 470, 'mesh': 'D019694'}, {'text': 'chronic hepatitis B', 'type': 'Disease', 'start': 525, 'end': 544, 'mesh': 'D019694'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 584, 'end': 594, 'mesh': 'D019259'}, {'text': 'HBeAg', 'type': 'Chemical', 'start': 840, 'end': 845, 'mesh': 'D006513'}, {'text': 'HBeAg', 'type': 'Chemical', 'start': 1024, 'end': 1029, 'mesh': 'D006513'}, {'text': 'HBeAg', 'type': 'Chemical', 'start': 1237, 'end': 1242, 'mesh': 'D006513'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 1325, 'end': 1335, 'mesh': 'D019259'}, {'text': 'chronic hepatitis B', 'type': 'Disease', 'start': 1360, 'end': 1379, 'mesh': 'D019694'}, {'text': 'lamivudine', 'type': 'Chemical', 'start': 1442, 'end': 1452, 'mesh': 'D019259'}, {'text': 'chronic hepatitis B', 'type': 'Disease', 'start': 1463, 'end': 1482, 'mesh': 'D019694'}]"
+1447,18025637,Branch retinal vein occlusion and fluoxetine.,"A case of branch retinal vein occlusion associated with fluoxetine-induced secondary hypertension is described. Although an infrequent complication of selective serotonin reuptake inhibitor therapy, it is important that ophthalmologists are aware that these agents can cause hypertension because this class of drugs is widely prescribed.","[{'text': 'retinal vein occlusion', 'type': 'Disease', 'start': 7, 'end': 29, 'mesh': 'D012170'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 34, 'end': 44, 'mesh': 'D005473'}, {'text': 'retinal vein occlusion', 'type': 'Disease', 'start': 63, 'end': 85, 'mesh': 'D012170'}, {'text': 'fluoxetine', 'type': 'Chemical', 'start': 102, 'end': 112, 'mesh': 'D005473'}, {'text': 'hypertension', 'type': 'Disease', 'start': 131, 'end': 143, 'mesh': 'D006973'}, {'text': 'serotonin', 'type': 'Chemical', 'start': 207, 'end': 216, 'mesh': 'D012701'}, {'text': 'hypertension', 'type': 'Disease', 'start': 321, 'end': 333, 'mesh': 'D006973'}]"
+1448,18165598,"The differential effects of bupivacaine and lidocaine on prostaglandin E2 release, cyclooxygenase gene expression and pain in a clinical pain model.","BACKGROUND: In addition to blocking nociceptive input from surgical sites, long-acting local anesthetics might directly modulate inflammation. In the present study, we describe the proinflammatory effects of bupivacaine on local prostaglandin E2 (PGE2) production and cyclooxygenase (COX) gene expression that increases postoperative pain in human subjects. METHODS: Subjects (n = 114) undergoing extraction of impacted third molars received either 2% lidocaine or 0.5% bupivacaine before surgery and either rofecoxib 50 mg or placebo orally 90 min before surgery and for the following 48 h. Oral mucosal biopsies were taken before surgery and 48 h after surgery. After extraction, a microdialysis probe was placed at the surgical site for PGE2 and thromboxane B2 (TXB2) measurements. RESULTS: The bupivacaine/rofecoxib group reported significantly less pain, as assessed by a visual analog scale, compared with the other three treatment groups over the first 4 h. However, the bupivacaine/placebo group reported significantly more pain at 24 h and PGE2 levels during the first 4 h were significantly higher than the other three treatment groups. Moreover, bupivacaine significantly increased COX-2 gene expression at 48 h as compared with the lidocaine/placebo group. Thromboxane levels were not significantly affected by any of the treatments, indicating that the effects seen were attributable to inhibition of COX-2, but not COX-1. CONCLUSIONS: These results suggest that bupivacaine stimulates COX-2 gene expression after tissue injury, which is associated with higher PGE2 production and pain after the local anesthetic effect dissipates.","[{'text': 'bupivacaine', 'type': 'Chemical', 'start': 28, 'end': 39, 'mesh': 'D002045'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 44, 'end': 53, 'mesh': 'D008012'}, {'text': 'prostaglandin E2', 'type': 'Chemical', 'start': 57, 'end': 73, 'mesh': 'D015232'}, {'text': 'pain', 'type': 'Disease', 'start': 118, 'end': 122, 'mesh': 'D010146'}, {'text': 'pain', 'type': 'Disease', 'start': 137, 'end': 141, 'mesh': 'D010146'}, {'text': 'inflammation', 'type': 'Disease', 'start': 278, 'end': 290, 'mesh': 'D007249'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 357, 'end': 368, 'mesh': 'D002045'}, {'text': 'prostaglandin E2', 'type': 'Chemical', 'start': 378, 'end': 394, 'mesh': 'D015232'}, {'text': 'PGE2', 'type': 'Chemical', 'start': 396, 'end': 400, 'mesh': 'D015232'}, {'text': 'postoperative pain', 'type': 'Disease', 'start': 469, 'end': 487, 'mesh': 'D010149'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 601, 'end': 610, 'mesh': 'D008012'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 619, 'end': 630, 'mesh': 'D002045'}, {'text': 'rofecoxib', 'type': 'Chemical', 'start': 657, 'end': 666, 'mesh': 'C116926'}, {'text': 'PGE2', 'type': 'Chemical', 'start': 889, 'end': 893, 'mesh': 'D015232'}, {'text': 'thromboxane B2', 'type': 'Chemical', 'start': 898, 'end': 912, 'mesh': 'D013929'}, {'text': 'TXB2', 'type': 'Chemical', 'start': 914, 'end': 918, 'mesh': 'D013929'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 947, 'end': 958, 'mesh': 'D002045'}, {'text': 'rofecoxib', 'type': 'Chemical', 'start': 959, 'end': 968, 'mesh': 'C116926'}, {'text': 'pain', 'type': 'Disease', 'start': 1003, 'end': 1007, 'mesh': 'D010146'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 1127, 'end': 1138, 'mesh': 'D002045'}, {'text': 'pain', 'type': 'Disease', 'start': 1181, 'end': 1185, 'mesh': 'D010146'}, {'text': 'PGE2', 'type': 'Chemical', 'start': 1198, 'end': 1202, 'mesh': 'D015232'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 1306, 'end': 1317, 'mesh': 'D002045'}, {'text': 'lidocaine', 'type': 'Chemical', 'start': 1393, 'end': 1402, 'mesh': 'D008012'}, {'text': 'Thromboxane', 'type': 'Chemical', 'start': 1418, 'end': 1429, 'mesh': 'D013931'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 1625, 'end': 1636, 'mesh': 'D002045'}, {'text': 'tissue injury', 'type': 'Disease', 'start': 1676, 'end': 1689, 'mesh': 'D017695'}, {'text': 'PGE2', 'type': 'Chemical', 'start': 1723, 'end': 1727, 'mesh': 'D015232'}, {'text': 'pain', 'type': 'Disease', 'start': 1743, 'end': 1747, 'mesh': 'D010146'}]"
+1449,18189308,p75NTR expression in rat urinary bladder sensory neurons and spinal cord with cyclophosphamide-induced cystitis.,"A role for nerve growth factor (NGF) in contributing to increased voiding frequency and altered sensation from the urinary bladder has been suggested. Previous studies have examined the expression and regulation of tyrosine kinase receptors (Trks) in micturition reflexes with urinary bladder inflammation. The present studies examine the expression and regulation of another receptor known to bind NGF, p75(NTR), after various durations of bladder inflammation induced by cyclophosphamide (CYP). CYP-induced cystitis increased (P < or = 0.001) p75(NTR) expression in the superficial lateral and medial dorsal horn in L1-L2 and L6-S1 spinal segments. The number of p75(NTR)-immunoreactive (-IR) cells in the lumbosacral dorsal root ganglia (DRG) also increased (P < or = 0.05) with CYP-induced cystitis (acute, intermediate, and chronic). Quantitative, real-time polymerase chain reaction also demonstrated significant increases (P < or = 0.01) in p75(NTR) mRNA in DRG with intermediate and chronic CYP-induced cystitis. Retrograde dye-tracing techniques with Fastblue were used to identify presumptive bladder afferent cells in the lumbosacral DRG. In bladder afferent cells in DRG, p75(NTR)-IR was also increased (P < or = 0.01) with cystitis. In addition to increases in p75(NTR)-IR in DRG cell bodies, increases (P < or = 0.001) in pericellular (encircling DRG cells) p75(NTR)-IR in DRG also increased. Confocal analyses demonstrated that pericellular p75(NTR)-IR was not colocalized with the glial marker, glial fibrillary acidic protein (GFAP). These studies demonstrate that p75(NTR) expression in micturition reflexes is present constitutively and modified by bladder inflammation. The functional significance of p75(NTR) expression in micturition reflexes remains to be determined.","[{'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 78, 'end': 94, 'mesh': 'D003520'}, {'text': 'cystitis', 'type': 'Disease', 'start': 103, 'end': 111, 'mesh': 'D003556'}, {'text': 'tyrosine', 'type': 'Chemical', 'start': 328, 'end': 336, 'mesh': 'D014443'}, {'text': 'urinary bladder inflammation', 'type': 'Disease', 'start': 390, 'end': 418, 'mesh': 'D003556'}, {'text': 'bladder inflammation', 'type': 'Disease', 'start': 554, 'end': 574, 'mesh': 'D003556'}, {'text': 'cyclophosphamide', 'type': 'Chemical', 'start': 586, 'end': 602, 'mesh': 'D003520'}, {'text': 'CYP', 'type': 'Chemical', 'start': 604, 'end': 607, 'mesh': 'D003520'}, {'text': 'CYP', 'type': 'Chemical', 'start': 610, 'end': 613, 'mesh': 'D003520'}, {'text': 'cystitis', 'type': 'Disease', 'start': 622, 'end': 630, 'mesh': 'D003556'}, {'text': 'CYP', 'type': 'Chemical', 'start': 895, 'end': 898, 'mesh': 'D003520'}, {'text': 'cystitis', 'type': 'Disease', 'start': 907, 'end': 915, 'mesh': 'D003556'}, {'text': 'CYP', 'type': 'Chemical', 'start': 1112, 'end': 1115, 'mesh': 'D003520'}, {'text': 'cystitis', 'type': 'Disease', 'start': 1124, 'end': 1132, 'mesh': 'D003556'}, {'text': 'cystitis', 'type': 'Disease', 'start': 1349, 'end': 1357, 'mesh': 'D003556'}, {'text': 'bladder inflammation', 'type': 'Disease', 'start': 1781, 'end': 1801, 'mesh': 'D003556'}]"
+1450,18340638,Azathioprine-induced suicidal erythrocyte death.,"BACKGROUND: Azathioprine is widely used as an immunosuppressive drug. The side effects of azathioprine include anemia, which has been attributed to bone marrow suppression. Alternatively, anemia could result from accelerated suicidal erythrocyte death or eryptosis, which is characterized by exposure of phosphatidylserine (PS) at the erythrocyte surface and by cell shrinkage. METHODS: The present experiments explored whether azathioprine influences eryptosis. According to annexin V binding, erythrocytes from patients indeed showed a significant increase of PS exposure within 1 week of treatment with azathioprine. In a second series, cytosolic Ca2+ activity (Fluo3 fluorescence), cell volume (forward scatter), and PS-exposure (annexin V binding) were determined by FACS analysis in erythrocytes from healthy volunteers. RESULTS: Exposure to azathioprine (> or =2 microg/mL) for 48 hours increased cytosolic Ca2+ activity and annexin V binding and decreased forward scatter. The effect of azathioprine on both annexin V binding and forward scatter was significantly blunted in the nominal absence of extracellular Ca2+. CONCLUSIONS: Azathioprine triggers suicidal erythrocyte death, an effect presumably contributing to azathioprine-induced anemia.","[{'text': 'Azathioprine', 'type': 'Chemical', 'start': 0, 'end': 12, 'mesh': 'D001379'}, {'text': 'Azathioprine', 'type': 'Chemical', 'start': 61, 'end': 73, 'mesh': 'D001379'}, {'text': 'azathioprine', 'type': 'Chemical', 'start': 139, 'end': 151, 'mesh': 'D001379'}, {'text': 'anemia', 'type': 'Disease', 'start': 160, 'end': 166, 'mesh': 'D000740'}, {'text': 'anemia', 'type': 'Disease', 'start': 237, 'end': 243, 'mesh': 'D000740'}, {'text': 'phosphatidylserine', 'type': 'Chemical', 'start': 353, 'end': 371, 'mesh': 'D010718'}, {'text': 'PS', 'type': 'Chemical', 'start': 373, 'end': 375, 'mesh': 'D010718'}, {'text': 'azathioprine', 'type': 'Chemical', 'start': 477, 'end': 489, 'mesh': 'D001379'}, {'text': 'PS', 'type': 'Chemical', 'start': 611, 'end': 613, 'mesh': 'D010718'}, {'text': 'azathioprine', 'type': 'Chemical', 'start': 655, 'end': 667, 'mesh': 'D001379'}, {'text': 'Ca', 'type': 'Chemical', 'start': 699, 'end': 701, 'mesh': 'D002118'}, {'text': 'Fluo3', 'type': 'Chemical', 'start': 714, 'end': 719, 'mesh': 'C059715'}, {'text': 'PS', 'type': 'Chemical', 'start': 770, 'end': 772, 'mesh': 'D010718'}, {'text': 'azathioprine', 'type': 'Chemical', 'start': 897, 'end': 909, 'mesh': 'D001379'}, {'text': 'Ca', 'type': 'Chemical', 'start': 963, 'end': 965, 'mesh': 'D002118'}, {'text': 'azathioprine', 'type': 'Chemical', 'start': 1044, 'end': 1056, 'mesh': 'D001379'}, {'text': 'Ca', 'type': 'Chemical', 'start': 1169, 'end': 1171, 'mesh': 'D002118'}, {'text': 'Azathioprine', 'type': 'Chemical', 'start': 1188, 'end': 1200, 'mesh': 'D001379'}, {'text': 'azathioprine', 'type': 'Chemical', 'start': 1275, 'end': 1287, 'mesh': 'D001379'}, {'text': 'anemia', 'type': 'Disease', 'start': 1296, 'end': 1302, 'mesh': 'D000740'}]"
+1451,18399341,Clinical comparison of cardiorespiratory effects during unilateral and conventional spinal anaesthesia.,"BACKGROUND: Spinal anaesthesia is widely employed in clinical practice but has the main drawback of post-spinal block hypotension. Efforts must therefore continue to be made to obviate this setback OBJECTIVE: To evaluate the cardiovascular and respiratory changes during unilateral and conventional spinal anaesthesia. METHODS: With ethical approval, we studied 74 American Society of Anesthesiologists (ASA), physical status class 1 and 2 patients scheduled for elective unilateral lower limb surgery. Patients were randomly allocated into one of two groups: lateral and conventional spinal anaesthesia groups. In the lateral position with operative side down, patients recived 10 mg (2mls) of 0.5% hyperbaric bupivacaine through a 25-gauge spinal needle. Patients in the unilateral group were maintained in the lateral position for 15 minutes following spinal injection while those in the conventional group were turned supine immediately after injection. Blood pressure, heart rate, respiratory rate and oxygen saturation were monitored over 1 hour. RESULTS: Three patients (8.1%) in the unilateral group and 5 (13.5%) in the conventional group developed hypotension, P= 0.71. Four (10.8%) patients in the conventional group and 1 (2.7%) in the unilateral group, P= 0.17 required epinephrine infusion to treat hypotension. Patients in the conventional group had statistically significant greater fall in the systolic blood pressures at 15, 30 and 45 minutes when compared to the baseline (P= 0.003, 0.001 and 0.004). The mean respiratory rate and oxygen saturations in the two groups were similar. CONCLUSION: Compared to conventional spinal anaesthesia, unilateral spinal anaesthesia was associated with fewer cardiovascular perturbations. Also, the type of spinal block instituted affected neither the respiratory rate nor the arterial oxygen saturation.","[{'text': 'hypotension', 'type': 'Disease', 'start': 222, 'end': 233, 'mesh': 'D007022'}, {'text': 'bupivacaine', 'type': 'Chemical', 'start': 815, 'end': 826, 'mesh': 'D002045'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 1111, 'end': 1117, 'mesh': 'D010100'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1262, 'end': 1273, 'mesh': 'D007022'}, {'text': 'epinephrine', 'type': 'Chemical', 'start': 1387, 'end': 1398, 'mesh': 'D004837'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1417, 'end': 1428, 'mesh': 'D007022'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 1654, 'end': 1660, 'mesh': 'D010100'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 1945, 'end': 1951, 'mesh': 'D010100'}]"
+1452,18422462,Spectrum of adverse events after generic HAART in southern Indian HIV-infected patients.,"To determine the incidence of clinically significant adverse events after long-term, fixed-dose, generic highly active antiretroviral therapy (HAART) use among HIV-infected individuals in South India, we examined the experiences of 3154 HIV-infected individuals who received a minimum of 3 months of generic HAART between February 1996 and December 2006 at a tertiary HIV care referral center in South India. The most common regimens were 3TC + d4T + nevirapine (NVP) (54.8%), zidovudine (AZT) + 3TC + NVP (14.5%), 3TC + d4T + efavirenz (EFV) (20.1%), and AZT + 3TC + EFV (5.4%). The most common adverse events and median CD4 at time of event were rash (15.2%; CD4, 285 cells/microL) and peripheral neuropathy (9.0% and 348 cells/microL). Clinically significant anemia (hemoglobin <7 g/dL) was observed in 5.4% of patients (CD4, 165 cells/microL) and hepatitis (clinical jaundice with alanine aminotransferase > 5 times upper limits of normal) in 3.5% of patients (CD4, 260 cells/microL). Women were significantly more likely to experience lactic acidosis, while men were significantly more likely to experience immune reconstitution syndrome (p < 0.05). Among the patients with 1 year of follow-up, NVP therapy was significantly associated with developing rash and d4T therapy with developing peripheral neuropathy (p < 0.05). Anemia and hepatitis often occur within 12 weeks of initiating generic HAART. Frequent and early monitoring for these toxicities is warranted in developing countries where generic HAART is increasingly available.","[{'text': 'HIV-infected', 'type': 'Disease', 'start': 66, 'end': 78, 'mesh': 'D015658'}, {'text': 'HIV-infected', 'type': 'Disease', 'start': 249, 'end': 261, 'mesh': 'D015658'}, {'text': 'HIV-infected', 'type': 'Disease', 'start': 326, 'end': 338, 'mesh': 'D015658'}, {'text': '3TC', 'type': 'Chemical', 'start': 528, 'end': 531, 'mesh': 'D019259'}, {'text': 'd4T', 'type': 'Chemical', 'start': 534, 'end': 537, 'mesh': 'D018119'}, {'text': 'nevirapine', 'type': 'Chemical', 'start': 540, 'end': 550, 'mesh': 'D019829'}, {'text': 'NVP', 'type': 'Chemical', 'start': 552, 'end': 555, 'mesh': 'D019829'}, {'text': 'zidovudine', 'type': 'Chemical', 'start': 566, 'end': 576, 'mesh': 'D015215'}, {'text': 'AZT', 'type': 'Chemical', 'start': 578, 'end': 581, 'mesh': 'D015215'}, {'text': '3TC', 'type': 'Chemical', 'start': 585, 'end': 588, 'mesh': 'D019259'}, {'text': 'NVP', 'type': 'Chemical', 'start': 591, 'end': 594, 'mesh': 'D019829'}, {'text': '3TC', 'type': 'Chemical', 'start': 604, 'end': 607, 'mesh': 'D019259'}, {'text': 'd4T', 'type': 'Chemical', 'start': 610, 'end': 613, 'mesh': 'D018119'}, {'text': 'efavirenz', 'type': 'Chemical', 'start': 616, 'end': 625, 'mesh': 'C098320'}, {'text': 'EFV', 'type': 'Chemical', 'start': 627, 'end': 630, 'mesh': 'C098320'}, {'text': 'AZT', 'type': 'Chemical', 'start': 645, 'end': 648, 'mesh': 'D015215'}, {'text': '3TC', 'type': 'Chemical', 'start': 651, 'end': 654, 'mesh': 'D019259'}, {'text': 'EFV', 'type': 'Chemical', 'start': 657, 'end': 660, 'mesh': 'C098320'}, {'text': 'rash', 'type': 'Disease', 'start': 737, 'end': 741, 'mesh': 'D005076'}, {'text': 'peripheral neuropathy', 'type': 'Disease', 'start': 777, 'end': 798, 'mesh': 'D010523'}, {'text': 'anemia', 'type': 'Disease', 'start': 851, 'end': 857, 'mesh': 'D000740'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 940, 'end': 949, 'mesh': 'D056486'}, {'text': 'jaundice', 'type': 'Disease', 'start': 960, 'end': 968, 'mesh': 'D007565'}, {'text': 'alanine', 'type': 'Chemical', 'start': 974, 'end': 981, 'mesh': 'D000409'}, {'text': 'lactic acidosis', 'type': 'Disease', 'start': 1129, 'end': 1144, 'mesh': 'D000140'}, {'text': 'immune reconstitution syndrome', 'type': 'Disease', 'start': 1201, 'end': 1231, 'mesh': 'D054019'}, {'text': 'NVP', 'type': 'Chemical', 'start': 1289, 'end': 1292, 'mesh': 'D019829'}, {'text': 'rash', 'type': 'Disease', 'start': 1346, 'end': 1350, 'mesh': 'D005076'}, {'text': 'd4T', 'type': 'Chemical', 'start': 1355, 'end': 1358, 'mesh': 'D018119'}, {'text': 'peripheral neuropathy', 'type': 'Disease', 'start': 1383, 'end': 1404, 'mesh': 'D010523'}, {'text': 'Anemia', 'type': 'Disease', 'start': 1417, 'end': 1423, 'mesh': 'D000740'}, {'text': 'hepatitis', 'type': 'Disease', 'start': 1428, 'end': 1437, 'mesh': 'D056486'}, {'text': 'toxicities', 'type': 'Disease', 'start': 1535, 'end': 1545, 'mesh': 'D064420'}]"
+1453,18450790,Thalidomide and sensory neurotoxicity: a neurophysiological study.,"BACKGROUND: Recent studies confirmed a high incidence of sensory axonal neuropathy in patients treated with different doses of thalidomide. The study's aims were to measure variations in sural nerve sensory action potential (SAP) amplitude in patients with refractory cutaneous lupus erythematosus (CLE) treated with thalidomide and use these findings to identify the neurotoxic potential of thalidomide and the recovery capacity of sensory fibres after discontinuation of treatment. PATIENTS AND METHODS: Clinical and electrophysiological data in 12 female patients with CLE during treatment with thalidomide and up to 47 months after discontinuation of treatment were analysed. Sural nerve SAP amplitude reduction > or =40% was the criteria for discontinuing therapy. RESULTS: During treatment, 11 patients showed a reduction in sural nerve SAP amplitude compared to baseline values (9 with a reduction > or =50% and 2 <50%). One patient showed no changes in SAP amplitude. Five patients complained of paresthesias and leg cramps. After thalidomide treatment, sural SAP amplitude recovered in 3 patients. At detection of reduction in sural nerve SAP amplitude, the median thalidomide cumulative dose was 21.4 g. The threshold neurotoxic dosage is lower than previously reported. CONCLUSIONS: Sural nerve SAP amplitude reduction is a reliable and sensitive marker of degeneration and recovery of sensory fibres. This electrophysiological parameter provides information about subclinical neurotoxic potential of thalidomide but is not helpful in predicting the appearance of sensory symptoms.","[{'text': 'Thalidomide', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D013792'}, {'text': 'sensory neurotoxicity', 'type': 'Disease', 'start': 16, 'end': 37, 'mesh': 'D010523'}, {'text': 'sensory axonal neuropathy', 'type': 'Disease', 'start': 124, 'end': 149, 'mesh': 'D010523'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 194, 'end': 205, 'mesh': 'D013792'}, {'text': 'cutaneous lupus erythematosus', 'type': 'Disease', 'start': 335, 'end': 364, 'mesh': 'D008178'}, {'text': 'CLE', 'type': 'Disease', 'start': 366, 'end': 369, 'mesh': 'D008178'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 384, 'end': 395, 'mesh': 'D013792'}, {'text': 'neurotoxic', 'type': 'Disease', 'start': 435, 'end': 445, 'mesh': 'D020258'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 459, 'end': 470, 'mesh': 'D013792'}, {'text': 'CLE', 'type': 'Disease', 'start': 639, 'end': 642, 'mesh': 'D008178'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 665, 'end': 676, 'mesh': 'D013792'}, {'text': 'paresthesias', 'type': 'Disease', 'start': 1071, 'end': 1083, 'mesh': 'D010292'}, {'text': 'cramps', 'type': 'Disease', 'start': 1092, 'end': 1098, 'mesh': 'D009120'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 1106, 'end': 1117, 'mesh': 'D013792'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 1241, 'end': 1252, 'mesh': 'D013792'}, {'text': 'neurotoxic', 'type': 'Disease', 'start': 1295, 'end': 1305, 'mesh': 'D020258'}, {'text': 'neurotoxic', 'type': 'Disease', 'start': 1555, 'end': 1565, 'mesh': 'D020258'}, {'text': 'thalidomide', 'type': 'Chemical', 'start': 1579, 'end': 1590, 'mesh': 'D013792'}]"
+1454,18801087,Amiodarone-related pulmonary mass and unique membranous glomerulonephritis in a patient with valvular heart disease: Diagnostic pitfall and new findings.,"Amiodarone is an anti-arrhythmic drug for life-threatening tachycardia, but various adverse effects have been reported. Reported herein is an autopsy case of valvular heart disease, in a patient who developed a lung mass (1.5 cm in diameter) and proteinuria (2.76 g/day) after treatment with amiodarone for a long time. The lung mass was highly suspected to be lung cancer on CT and positron emission tomography, but histologically the lesion was composed of lymphoplasmacytic infiltrates in alveolar walls and intra-alveolar accumulation of foamy macrophages containing characteristic myelinoid bodies, indicating that it was an amiodarone-related lesion. In addition, the lung tissue had unevenly distributed hemosiderin deposition, and abnormally tortuous capillaries were seen in the mass and in heavily hemosiderotic lung portions outside the mass. In the kidneys, glomeruli had membrane spikes, prominent swelling of podocytes and subepithelial deposits, which were sometimes large and hump-like. Autoimmune diseases, viral hepatitis, malignant neoplasms or other diseases with a known relationship to membranous glomerulonephritis were not found. The present case highlights the possibility that differential diagnosis between an amiodarone-related pulmonary lesion and a neoplasm can be very difficult radiologically, and suggests that membranous glomerulonephritis might be another possible complication of amiodarone treatment.","[{'text': 'Amiodarone', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D000638'}, {'text': 'pulmonary mass', 'type': 'Disease', 'start': 19, 'end': 33, 'mesh': 'D055370'}, {'text': 'membranous glomerulonephritis', 'type': 'Disease', 'start': 45, 'end': 74, 'mesh': 'D015433'}, {'text': 'valvular heart disease', 'type': 'Disease', 'start': 93, 'end': 115, 'mesh': 'D006349'}, {'text': 'Amiodarone', 'type': 'Chemical', 'start': 154, 'end': 164, 'mesh': 'D000638'}, {'text': 'arrhythmic', 'type': 'Disease', 'start': 176, 'end': 186, 'mesh': 'D001145'}, {'text': 'tachycardia', 'type': 'Disease', 'start': 213, 'end': 224, 'mesh': 'D013610'}, {'text': 'valvular heart disease', 'type': 'Disease', 'start': 312, 'end': 334, 'mesh': 'D006349'}, {'text': 'lung mass', 'type': 'Disease', 'start': 365, 'end': 374, 'mesh': 'D055370'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 400, 'end': 411, 'mesh': 'D011507'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 446, 'end': 456, 'mesh': 'D000638'}, {'text': 'lung mass', 'type': 'Disease', 'start': 478, 'end': 487, 'mesh': 'D055370'}, {'text': 'lung cancer', 'type': 'Disease', 'start': 515, 'end': 526, 'mesh': 'D008175'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 784, 'end': 794, 'mesh': 'D000638'}, {'text': 'hemosiderin', 'type': 'Disease', 'start': 865, 'end': 876, 'mesh': 'D006486'}, {'text': 'hemosiderotic', 'type': 'Disease', 'start': 962, 'end': 975, 'mesh': 'D006486'}, {'text': 'Autoimmune diseases', 'type': 'Disease', 'start': 1157, 'end': 1176, 'mesh': 'D001327'}, {'text': 'viral hepatitis', 'type': 'Disease', 'start': 1178, 'end': 1193, 'mesh': 'D006525'}, {'text': 'neoplasms', 'type': 'Disease', 'start': 1205, 'end': 1214, 'mesh': 'D009369'}, {'text': 'membranous glomerulonephritis', 'type': 'Disease', 'start': 1262, 'end': 1291, 'mesh': 'D015433'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 1391, 'end': 1401, 'mesh': 'D000638'}, {'text': 'pulmonary lesion', 'type': 'Disease', 'start': 1410, 'end': 1426, 'mesh': 'D055370'}, {'text': 'neoplasm', 'type': 'Disease', 'start': 1433, 'end': 1441, 'mesh': 'D009369'}, {'text': 'membranous glomerulonephritis', 'type': 'Disease', 'start': 1498, 'end': 1527, 'mesh': 'D015433'}, {'text': 'amiodarone', 'type': 'Chemical', 'start': 1570, 'end': 1580, 'mesh': 'D000638'}]"
+1455,18945509,Risk of coronary artery disease associated with initial sulphonylurea treatment of patients with type 2 diabetes: a matched case-control study.,"AIMS: This study sought to assess the risk of developing coronary artery disease (CAD) associated with initial treatment of type 2 diabetes with different sulphonylureas. METHODS: In type 2 diabetic patients, cases who developed CAD were compared retrospectively with controls that did not. The 20-year risk of CAD at diagnosis of diabetes, using the UKPDS risk engine, was used to match cases with controls. RESULTS: The 76 cases of CAD were compared with 152 controls. The hazard of developing CAD (95% CI) associated with initial treatment increased by 2.4-fold (1.3-4.3, P=0.004) with glibenclamide; 2-fold (0.9-4.6, P=0.099) with glipizide; 2.9-fold (1.6-5.1, P=0.000) with either, and was unchanged with metformin. The hazard decreased 0.3-fold (0.7-1.7, P=0.385) with glimepiride, 0.4-fold (0.7-1.3, P=0.192) with gliclazide, and 0.4-fold (0.7-1.1, P=0.09) with either. CONCLUSIONS: Initiating treatment of type 2 diabetes with glibenclamide or glipizide is associated with increased risk of CAD in comparison to gliclazide or glimepiride. If confirmed, this may be important because most Indian patients receive the cheaper older sulphonylureas, and present guidelines do not distinguish between individual agents.","[{'text': 'coronary artery disease', 'type': 'Disease', 'start': 8, 'end': 31, 'mesh': 'D003324'}, {'text': 'sulphonylurea', 'type': 'Chemical', 'start': 56, 'end': 69, 'mesh': '-1'}, {'text': 'type 2 diabetes', 'type': 'Disease', 'start': 97, 'end': 112, 'mesh': 'D003924'}, {'text': 'coronary artery disease', 'type': 'Disease', 'start': 201, 'end': 224, 'mesh': 'D003324'}, {'text': 'CAD', 'type': 'Disease', 'start': 226, 'end': 229, 'mesh': 'D003324'}, {'text': 'type 2 diabetes', 'type': 'Disease', 'start': 268, 'end': 283, 'mesh': 'D003924'}, {'text': 'sulphonylureas', 'type': 'Chemical', 'start': 299, 'end': 313, 'mesh': '-1'}, {'text': 'type 2 diabetic', 'type': 'Disease', 'start': 327, 'end': 342, 'mesh': 'D003924'}, {'text': 'CAD', 'type': 'Disease', 'start': 373, 'end': 376, 'mesh': 'D003324'}, {'text': 'CAD', 'type': 'Disease', 'start': 455, 'end': 458, 'mesh': 'D003324'}, {'text': 'diabetes', 'type': 'Disease', 'start': 475, 'end': 483, 'mesh': 'D003920'}, {'text': 'CAD', 'type': 'Disease', 'start': 578, 'end': 581, 'mesh': 'D003324'}, {'text': 'CAD', 'type': 'Disease', 'start': 640, 'end': 643, 'mesh': 'D003324'}, {'text': 'glibenclamide', 'type': 'Chemical', 'start': 733, 'end': 746, 'mesh': 'D005905'}, {'text': 'glipizide', 'type': 'Chemical', 'start': 779, 'end': 788, 'mesh': 'D005913'}, {'text': 'metformin', 'type': 'Chemical', 'start': 854, 'end': 863, 'mesh': 'D008687'}, {'text': 'glimepiride', 'type': 'Chemical', 'start': 919, 'end': 930, 'mesh': 'C057619'}, {'text': 'gliclazide', 'type': 'Chemical', 'start': 965, 'end': 975, 'mesh': 'D005907'}, {'text': 'type 2 diabetes', 'type': 'Disease', 'start': 1058, 'end': 1073, 'mesh': 'D003924'}, {'text': 'glibenclamide', 'type': 'Chemical', 'start': 1079, 'end': 1092, 'mesh': 'D005905'}, {'text': 'glipizide', 'type': 'Chemical', 'start': 1096, 'end': 1105, 'mesh': 'D005913'}, {'text': 'CAD', 'type': 'Disease', 'start': 1143, 'end': 1146, 'mesh': 'D003324'}, {'text': 'gliclazide', 'type': 'Chemical', 'start': 1164, 'end': 1174, 'mesh': 'D005907'}, {'text': 'glimepiride', 'type': 'Chemical', 'start': 1178, 'end': 1189, 'mesh': 'C057619'}, {'text': 'sulphonylureas', 'type': 'Chemical', 'start': 1282, 'end': 1296, 'mesh': '-1'}]"
+1456,18987260,Reduced progression of adriamycin nephropathy in spontaneously hypertensive rats treated by losartan.,"BACKGROUND: The aim of the study was to investigate the antihypertensive effects of angiotensin II type-1 receptor blocker, losartan, and its potential in slowing down renal disease progression in spontaneously hypertensive rats (SHR) with adriamycin (ADR) nephropathy. METHODS: Six-month-old female SHR were randomly selected in six groups. Two control groups (SH(6), SH(12)) received vehicle. Groups ADR(6), ADR+LOS(6) and ADR(12), and ADR+LOS(12) received ADR (2 mg/kg/b.w. i.v.) twice in a 3-week interval. Group ADR+LOS(6) received losartan (10 mg/kg/b.w./day by gavages) for 6 weeks and group ADR+LOS(12) for 12 weeks after second injection of ADR. Animals were killed after 6 or 12 weeks, respectively. Haemodynamic measurements were performed on anaesthetized animals, blood and urine samples were taken for biochemical analysis and the left kidney was processed for morphological studies. RESULTS: Short-term losartan treatment, besides antihypertensive effect, improved glomerular filtration rate and ameliorated glomerulosclerosis resulting in decreased proteinuria. Prolonged treatment with losartan showed further reduction of glomerulosclerosis associated with reduced progression of tubular atrophy and interstitial fibrosis, thus preventing heavy proteinuria and chronic renal failure. Losartan reduced uraemia and increased urea clearance in advanced ADR nephropathy in SHR. Histological examination showed that losartan could prevent tubular atrophy, interstitial infiltration and fibrosis in ADR nephropathy. CONCLUSION: Losartan reduces the rate of progression of ADR-induced focal segmental glomerulosclerosis to end-stage renal disease in SHR.","[{'text': 'adriamycin', 'type': 'Chemical', 'start': 23, 'end': 33, 'mesh': 'D004317'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 34, 'end': 45, 'mesh': 'D007674'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 63, 'end': 75, 'mesh': 'D006973'}, {'text': 'losartan', 'type': 'Chemical', 'start': 92, 'end': 100, 'mesh': 'D019808'}, {'text': 'angiotensin II', 'type': 'Chemical', 'start': 186, 'end': 200, 'mesh': 'D000804'}, {'text': 'losartan', 'type': 'Chemical', 'start': 226, 'end': 234, 'mesh': 'D019808'}, {'text': 'renal disease', 'type': 'Disease', 'start': 270, 'end': 283, 'mesh': 'D007674'}, {'text': 'hypertensive', 'type': 'Disease', 'start': 313, 'end': 325, 'mesh': 'D006973'}, {'text': 'adriamycin', 'type': 'Chemical', 'start': 342, 'end': 352, 'mesh': 'D004317'}, {'text': 'ADR', 'type': 'Chemical', 'start': 354, 'end': 357, 'mesh': 'D004317'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 359, 'end': 370, 'mesh': 'D007674'}, {'text': 'ADR', 'type': 'Chemical', 'start': 504, 'end': 507, 'mesh': 'D004317'}, {'text': 'ADR', 'type': 'Chemical', 'start': 512, 'end': 515, 'mesh': 'D004317'}, {'text': 'LOS', 'type': 'Chemical', 'start': 516, 'end': 519, 'mesh': 'D019808'}, {'text': 'ADR', 'type': 'Chemical', 'start': 527, 'end': 530, 'mesh': 'D004317'}, {'text': 'ADR', 'type': 'Chemical', 'start': 540, 'end': 543, 'mesh': 'D004317'}, {'text': 'LOS', 'type': 'Chemical', 'start': 544, 'end': 547, 'mesh': 'D019808'}, {'text': 'ADR', 'type': 'Chemical', 'start': 561, 'end': 564, 'mesh': 'D004317'}, {'text': 'ADR', 'type': 'Chemical', 'start': 619, 'end': 622, 'mesh': 'D004317'}, {'text': 'LOS', 'type': 'Chemical', 'start': 623, 'end': 626, 'mesh': 'D019808'}, {'text': 'losartan', 'type': 'Chemical', 'start': 639, 'end': 647, 'mesh': 'D019808'}, {'text': 'ADR', 'type': 'Chemical', 'start': 701, 'end': 704, 'mesh': 'D004317'}, {'text': 'LOS', 'type': 'Chemical', 'start': 705, 'end': 708, 'mesh': 'D019808'}, {'text': 'ADR', 'type': 'Chemical', 'start': 752, 'end': 755, 'mesh': 'D004317'}, {'text': 'losartan', 'type': 'Chemical', 'start': 1020, 'end': 1028, 'mesh': 'D019808'}, {'text': 'glomerulosclerosis', 'type': 'Disease', 'start': 1125, 'end': 1143, 'mesh': 'D005921'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1167, 'end': 1178, 'mesh': 'D011507'}, {'text': 'losartan', 'type': 'Chemical', 'start': 1205, 'end': 1213, 'mesh': 'D019808'}, {'text': 'glomerulosclerosis', 'type': 'Disease', 'start': 1242, 'end': 1260, 'mesh': 'D005921'}, {'text': 'atrophy', 'type': 'Disease', 'start': 1308, 'end': 1315, 'mesh': 'D001284'}, {'text': 'interstitial fibrosis', 'type': 'Disease', 'start': 1320, 'end': 1341, 'mesh': 'D005355'}, {'text': 'proteinuria', 'type': 'Disease', 'start': 1365, 'end': 1376, 'mesh': 'D011507'}, {'text': 'chronic renal failure', 'type': 'Disease', 'start': 1381, 'end': 1402, 'mesh': 'D007676'}, {'text': 'Losartan', 'type': 'Chemical', 'start': 1404, 'end': 1412, 'mesh': 'D019808'}, {'text': 'uraemia', 'type': 'Disease', 'start': 1421, 'end': 1428, 'mesh': 'D014511'}, {'text': 'urea', 'type': 'Chemical', 'start': 1443, 'end': 1447, 'mesh': 'D014508'}, {'text': 'ADR', 'type': 'Chemical', 'start': 1470, 'end': 1473, 'mesh': 'D004317'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1474, 'end': 1485, 'mesh': 'D007674'}, {'text': 'losartan', 'type': 'Chemical', 'start': 1531, 'end': 1539, 'mesh': 'D019808'}, {'text': 'atrophy', 'type': 'Disease', 'start': 1562, 'end': 1569, 'mesh': 'D001284'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 1601, 'end': 1609, 'mesh': 'D005355'}, {'text': 'ADR', 'type': 'Chemical', 'start': 1613, 'end': 1616, 'mesh': 'D004317'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1617, 'end': 1628, 'mesh': 'D007674'}, {'text': 'Losartan', 'type': 'Chemical', 'start': 1642, 'end': 1650, 'mesh': 'D019808'}, {'text': 'ADR', 'type': 'Chemical', 'start': 1686, 'end': 1689, 'mesh': 'D004317'}, {'text': 'focal segmental glomerulosclerosis', 'type': 'Disease', 'start': 1698, 'end': 1732, 'mesh': 'D005923'}, {'text': 'end-stage renal disease', 'type': 'Disease', 'start': 1736, 'end': 1759, 'mesh': 'D007676'}]"
+1457,19020118,The risks of aprotinin and tranexamic acid in cardiac surgery: a one-year follow-up of 1188 consecutive patients.,"BACKGROUND: Our aim was to investigate postoperative complications and mortality after administration of aprotinin compared to tranexamic acid in an unselected, consecutive cohort. METHODS: Perioperative data from consecutive cardiac surgery patients were prospectively collected between September 2005 and June 2006 in a university-affiliated clinic (n = 1188). During the first 5 mo, 596 patients received aprotinin (Group A); in the next 5 mo, 592 patients were treated with tranexamic acid (Group T). Except for antifibrinolytic therapy, the anesthetic and surgical protocols remained unchanged. RESULTS: The pre- and intraoperative variables were comparable between the treatment groups. Postoperatively, a significantly higher incidence of seizures was found in Group T (4.6% vs 1.2%, P < 0.001). This difference was also significant in the primary valve surgery and the high risk surgery subgroups (7.9% vs 1.2%, P = 0.003; 7.3% vs 2.4%, P = 0.035, respectively). Persistent atrial fibrillation (7.9% vs 2.3%, P = 0.020) and renal failure (9.7% vs 1.7%, P = 0.002) were also more common in Group T, in the primary valve surgery subgroup. On the contrary, among primary coronary artery bypass surgery patients, there were more acute myocardial infarctions and renal dysfunction in Group A (5.8% vs 2.0%, P = 0.027; 22.5% vs 15.2%, P = 0.036, respectively). The 1-yr mortality was significantly higher after aprotinin treatment in the high risk surgery group (17.7% vs 9.8%, P = 0.034). CONCLUSION: Both antifibrinolytic drugs bear the risk of adverse outcome depending on the type of cardiac surgery. Administration of aprotinin should be avoided in coronary artery bypass graft and high risk patients, whereas administration of tranexamic acid is not recommended in valve surgery.","[{'text': 'tranexamic acid', 'type': 'Chemical', 'start': 27, 'end': 42, 'mesh': 'D014148'}, {'text': 'tranexamic acid', 'type': 'Chemical', 'start': 241, 'end': 256, 'mesh': 'D014148'}, {'text': 'tranexamic acid', 'type': 'Chemical', 'start': 592, 'end': 607, 'mesh': 'D014148'}, {'text': 'seizures', 'type': 'Disease', 'start': 860, 'end': 868, 'mesh': 'D012640'}, {'text': 'renal failure', 'type': 'Disease', 'start': 1146, 'end': 1159, 'mesh': 'D051437'}, {'text': 'myocardial infarctions', 'type': 'Disease', 'start': 1353, 'end': 1375, 'mesh': 'D009203'}, {'text': 'renal dysfunction', 'type': 'Disease', 'start': 1380, 'end': 1397, 'mesh': 'D007674'}, {'text': 'tranexamic acid', 'type': 'Chemical', 'start': 1849, 'end': 1864, 'mesh': 'D014148'}]"
+1458,19108278,The biological properties of the optical isomers of propranolol and their effects on cardiac arrhythmias.,"1. The optical isomers of propranolol have been compared for their beta-blocking and antiarrhythmic activities.2. In blocking the positive inotropic and chronotropic responses to isoprenaline, (+)-propranolol had less than one hundredth the potency of (-)-propranolol. At dose levels of (+)-propranolol which attenuated the responses to isoprenaline, there was a significant prolongation of the PR interval of the electrocardiogram.3. The metabolic responses to isoprenaline in dogs (an increase in circulating glucose, lactate and free fatty acids) were all blocked by (-)-propranolol. (+)-Propranolol had no effect on fatty acid mobilization but significantly reduced the increments in both lactate and glucose.4. Both isomers of propranolol possessed similar depressant potency on isolated atrial muscle taken from guinea-pigs.5. The isomers of propranolol exhibited similar local anaesthetic potencies on an isolated frog nerve preparation at a level approximately three times that of procaine. The racemic compound was significantly less potent than either isomer.6. Both isomers of propranolol were capable of preventing adrenaline-induced cardiac arrhythmias in cats anaesthetized with halothane, but the mean dose of (-)-propranolol was 0.09+/-0.02 mg/kg whereas that of (+)-propranolol was 4.2+/-1.2 mg/kg. At the effective dose level of (+)-propranolol there was a significant prolongation of the PR interval of the electrocardiogram. Blockade of arrhythmias with both isomers was surmountable by increasing the dose of adrenaline.7. Both isomers of propranolol were also capable of reversing ventricular tachycardia caused by ouabain in anaesthetized cats and dogs. The dose of (-)-propranolol was significantly smaller than that of (+)-propranolol in both species but much higher than that required to produce evidence of beta-blockade.8. The implications of these results are discussed.","[{'text': 'propranolol', 'type': 'Chemical', 'start': 52, 'end': 63, 'mesh': 'D011433'}, {'text': 'cardiac arrhythmias', 'type': 'Disease', 'start': 85, 'end': 104, 'mesh': 'D001145'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 132, 'end': 143, 'mesh': 'D011433'}, {'text': 'isoprenaline', 'type': 'Chemical', 'start': 285, 'end': 297, 'mesh': 'D007545'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 303, 'end': 314, 'mesh': 'D011433'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 362, 'end': 373, 'mesh': 'D011433'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 397, 'end': 408, 'mesh': 'D011433'}, {'text': 'isoprenaline', 'type': 'Chemical', 'start': 443, 'end': 455, 'mesh': 'D007545'}, {'text': 'isoprenaline', 'type': 'Chemical', 'start': 568, 'end': 580, 'mesh': 'D007545'}, {'text': 'glucose', 'type': 'Chemical', 'start': 617, 'end': 624, 'mesh': 'D005947'}, {'text': 'lactate', 'type': 'Chemical', 'start': 626, 'end': 633, 'mesh': 'D019344'}, {'text': 'fatty acids', 'type': 'Chemical', 'start': 643, 'end': 654, 'mesh': 'D005227'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 680, 'end': 691, 'mesh': 'D011433'}, {'text': 'Propranolol', 'type': 'Chemical', 'start': 697, 'end': 708, 'mesh': 'D011433'}, {'text': 'fatty acid', 'type': 'Chemical', 'start': 726, 'end': 736, 'mesh': 'D005227'}, {'text': 'lactate', 'type': 'Chemical', 'start': 799, 'end': 806, 'mesh': 'D019344'}, {'text': 'glucose', 'type': 'Chemical', 'start': 811, 'end': 818, 'mesh': 'D005947'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 838, 'end': 849, 'mesh': 'D011433'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 954, 'end': 965, 'mesh': 'D011433'}, {'text': 'procaine', 'type': 'Chemical', 'start': 1095, 'end': 1103, 'mesh': 'D011343'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 1194, 'end': 1205, 'mesh': 'D011433'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 1233, 'end': 1243, 'mesh': 'D004837'}, {'text': 'cardiac arrhythmias', 'type': 'Disease', 'start': 1252, 'end': 1271, 'mesh': 'D001145'}, {'text': 'halothane', 'type': 'Chemical', 'start': 1299, 'end': 1308, 'mesh': 'D006221'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 1335, 'end': 1346, 'mesh': 'D011433'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 1389, 'end': 1400, 'mesh': 'D011433'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 1457, 'end': 1468, 'mesh': 'D011433'}, {'text': 'arrhythmias', 'type': 'Disease', 'start': 1563, 'end': 1574, 'mesh': 'D001145'}, {'text': 'adrenaline', 'type': 'Chemical', 'start': 1636, 'end': 1646, 'mesh': 'D004837'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 1666, 'end': 1677, 'mesh': 'D011433'}, {'text': 'ventricular tachycardia', 'type': 'Disease', 'start': 1709, 'end': 1732, 'mesh': 'D017180'}, {'text': 'ouabain', 'type': 'Chemical', 'start': 1743, 'end': 1750, 'mesh': 'D010042'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 1799, 'end': 1810, 'mesh': 'D011433'}, {'text': 'propranolol', 'type': 'Chemical', 'start': 1854, 'end': 1865, 'mesh': 'D011433'}]"
+1459,19139825,Topotecan in combination with radiotherapy in unresectable glioblastoma: a phase 2 study.,"Improving glioblastoma multiforme (GBM) treatment with radio-chemotherapy remains a challenge. Topotecan is an attractive option as it exhibits growth inhibition of human glioma as well as brain penetration. The present study assessed the combination of radiotherapy (60 Gy/30 fractions/40 days) and topotecan (0.9 mg/m(2)/day on days 1-5 on weeks 1, 3 and 5) in 50 adults with histologically proven and untreated GBM. The incidence of non-hematological toxicities was low and grade 3-4 hematological toxicities were reported in 20 patients (mainly lymphopenia and neutropenia). Partial response and stabilization rates were 2% and 32%, respectively, with an overall time to progression of 12 weeks. One-year overall survival (OS) rate was 42%, with a median OS of 40 weeks. Topotecan in combination with radiotherapy was well tolerated. However, while response and stabilization concerned one-third of the patients, the study did not show increased benefits in terms of survival in patients with unresectable GBM.","[{'text': 'Topotecan', 'type': 'Chemical', 'start': 0, 'end': 9, 'mesh': 'D019772'}, {'text': 'glioblastoma', 'type': 'Disease', 'start': 59, 'end': 71, 'mesh': 'D005909'}, {'text': 'glioblastoma multiforme', 'type': 'Disease', 'start': 100, 'end': 123, 'mesh': 'D005909'}, {'text': 'GBM', 'type': 'Disease', 'start': 125, 'end': 128, 'mesh': 'D005909'}, {'text': 'Topotecan', 'type': 'Chemical', 'start': 185, 'end': 194, 'mesh': 'D019772'}, {'text': 'glioma', 'type': 'Disease', 'start': 261, 'end': 267, 'mesh': 'D005910'}, {'text': 'topotecan', 'type': 'Chemical', 'start': 390, 'end': 399, 'mesh': 'D019772'}, {'text': 'GBM', 'type': 'Disease', 'start': 504, 'end': 507, 'mesh': 'D005909'}, {'text': 'toxicities', 'type': 'Disease', 'start': 544, 'end': 554, 'mesh': 'D064420'}, {'text': 'toxicities', 'type': 'Disease', 'start': 591, 'end': 601, 'mesh': 'D064420'}, {'text': 'lymphopenia', 'type': 'Disease', 'start': 639, 'end': 650, 'mesh': 'D008231'}, {'text': 'neutropenia', 'type': 'Disease', 'start': 655, 'end': 666, 'mesh': 'D009503'}, {'text': 'Topotecan', 'type': 'Chemical', 'start': 865, 'end': 874, 'mesh': 'D019772'}, {'text': 'GBM', 'type': 'Disease', 'start': 1100, 'end': 1103, 'mesh': 'D005909'}]"
+1460,19154241,Long-term lithium therapy leading to hyperparathyroidism: a case report.,"PURPOSE: This paper reviews the effect of chronic lithium therapy on serum calcium level and parathyroid glands, its pathogenesis, and treatment options. We examined the case of a lithium-treated patient who had recurrent hypercalcemia to better understand the disease process. CONCLUSION: Primary hyperparathyroidism is a rare but potentially life-threatening side effect of long-term lithium therapy. Careful patient selection and long-term follow-up can reduce morbidity. PRACTICAL IMPLICATIONS: As much as 15% of lithium-treated patients become hypercalcemic. By routinely monitoring serum calcium levels, healthcare providers can improve the quality of life of this patient group.","[{'text': 'lithium', 'type': 'Chemical', 'start': 10, 'end': 17, 'mesh': 'D008094'}, {'text': 'hyperparathyroidism', 'type': 'Disease', 'start': 37, 'end': 56, 'mesh': 'D006961'}, {'text': 'lithium', 'type': 'Chemical', 'start': 123, 'end': 130, 'mesh': 'D008094'}, {'text': 'calcium', 'type': 'Chemical', 'start': 148, 'end': 155, 'mesh': 'D002118'}, {'text': 'lithium', 'type': 'Chemical', 'start': 253, 'end': 260, 'mesh': 'D008094'}, {'text': 'hypercalcemia', 'type': 'Disease', 'start': 295, 'end': 308, 'mesh': 'D006934'}, {'text': 'Primary hyperparathyroidism', 'type': 'Disease', 'start': 363, 'end': 390, 'mesh': 'D049950'}, {'text': 'lithium', 'type': 'Chemical', 'start': 459, 'end': 466, 'mesh': 'D008094'}, {'text': 'lithium', 'type': 'Chemical', 'start': 590, 'end': 597, 'mesh': 'D008094'}, {'text': 'hypercalcemic', 'type': 'Disease', 'start': 622, 'end': 635, 'mesh': 'D006934'}, {'text': 'calcium', 'type': 'Chemical', 'start': 667, 'end': 674, 'mesh': 'D002118'}]"
+1461,19178808,Comparison of laryngeal mask with endotracheal tube for anesthesia in endoscopic sinus surgery.,"BACKGROUND: The purpose of this study was to compare surgical conditions, including the amount of intraoperative bleeding as well as intraoperative blood pressure, during functional endoscopic sinus surgery (FESS) using flexible reinforced laryngeal mask airway (FRLMA) versus endotracheal tube (ETT) in maintaining controlled hypotension anesthesia induced by propofol-remifentanil total i.v. anesthesia (TIVA). METHODS: Sixty normotensive American Society of Anesthesiologists I-II adult patients undergoing FESS under controlled hypotension anesthesia caused by propofol-remifentanil-TIVA were randomly assigned into two groups: group I, FRLMA; group II, ETT. Hemorrhage was measured and the visibility of the operative field was evaluated according to a six-point scale. RESULTS: Controlled hypotension was achieved within a shorter period using laryngeal mask using lower rates of remifentanil infusion and lower total dose of remifentanil. CONCLUSION: In summary, our results indicate that airway management using FRLMA during controlled hypotension anesthesia provided better surgical conditions in terms of quality of operative field and blood loss and allowed for convenient induced hypotension with low doses of remifentanil during TIVA in patients undergoing FESS.","[{'text': 'bleeding', 'type': 'Disease', 'start': 209, 'end': 217, 'mesh': 'D006470'}, {'text': 'hypotension', 'type': 'Disease', 'start': 423, 'end': 434, 'mesh': 'D007022'}, {'text': 'propofol', 'type': 'Chemical', 'start': 457, 'end': 465, 'mesh': 'D015742'}, {'text': 'remifentanil', 'type': 'Chemical', 'start': 466, 'end': 478, 'mesh': 'C071741'}, {'text': 'hypotension', 'type': 'Disease', 'start': 628, 'end': 639, 'mesh': 'D007022'}, {'text': 'propofol', 'type': 'Chemical', 'start': 661, 'end': 669, 'mesh': 'D015742'}, {'text': 'remifentanil', 'type': 'Chemical', 'start': 670, 'end': 682, 'mesh': 'C071741'}, {'text': 'Hemorrhage', 'type': 'Disease', 'start': 759, 'end': 769, 'mesh': 'D006470'}, {'text': 'hypotension', 'type': 'Disease', 'start': 891, 'end': 902, 'mesh': 'D007022'}, {'text': 'remifentanil', 'type': 'Chemical', 'start': 982, 'end': 994, 'mesh': 'C071741'}, {'text': 'remifentanil', 'type': 'Chemical', 'start': 1028, 'end': 1040, 'mesh': 'C071741'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1140, 'end': 1151, 'mesh': 'D007022'}, {'text': 'hypotension', 'type': 'Disease', 'start': 1288, 'end': 1299, 'mesh': 'D007022'}, {'text': 'remifentanil', 'type': 'Chemical', 'start': 1318, 'end': 1330, 'mesh': 'C071741'}]"
+1462,19184102,Nonalcoholic fatty liver disease during valproate therapy.,"Valproic acid (VPA) is effective for the treatment of many types of epilepsy, but its use can be associated with an increase in body weight. We report a case of nonalcoholic fatty liver disease (NAFLD) arising in a child who developed obesity during VPA treatment. Laboratory data revealed hyperinsulinemia with insulin resistance. After the withdrawal of VPA therapy, our patient showed a significant weight loss, a decrease of body mass index, and normalization of metabolic and endocrine parameters; moreover, ultrasound measurements showed a complete normalization. The present case suggests that obesity, hyperinsulinemia, insulin resistance, and long-term treatment with VPA may be all associated with the development of NAFLD; this side effect is reversible after VPA withdrawal.","[{'text': 'Nonalcoholic fatty liver disease', 'type': 'Disease', 'start': 0, 'end': 32, 'mesh': 'D065626'}, {'text': 'valproate', 'type': 'Chemical', 'start': 40, 'end': 49, 'mesh': 'D014635'}, {'text': 'Valproic acid', 'type': 'Chemical', 'start': 59, 'end': 72, 'mesh': 'D014635'}, {'text': 'VPA', 'type': 'Chemical', 'start': 74, 'end': 77, 'mesh': 'D014635'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 127, 'end': 135, 'mesh': 'D004827'}, {'text': 'nonalcoholic fatty liver disease', 'type': 'Disease', 'start': 220, 'end': 252, 'mesh': 'D065626'}, {'text': 'NAFLD', 'type': 'Disease', 'start': 254, 'end': 259, 'mesh': 'D065626'}, {'text': 'obesity', 'type': 'Disease', 'start': 294, 'end': 301, 'mesh': 'D009765'}, {'text': 'VPA', 'type': 'Chemical', 'start': 309, 'end': 312, 'mesh': 'D014635'}, {'text': 'hyperinsulinemia', 'type': 'Disease', 'start': 349, 'end': 365, 'mesh': 'D006946'}, {'text': 'insulin resistance', 'type': 'Disease', 'start': 371, 'end': 389, 'mesh': 'D007333'}, {'text': 'VPA', 'type': 'Chemical', 'start': 415, 'end': 418, 'mesh': 'D014635'}, {'text': 'weight loss', 'type': 'Disease', 'start': 461, 'end': 472, 'mesh': 'D015431'}, {'text': 'obesity', 'type': 'Disease', 'start': 660, 'end': 667, 'mesh': 'D009765'}, {'text': 'hyperinsulinemia', 'type': 'Disease', 'start': 669, 'end': 685, 'mesh': 'D006946'}, {'text': 'insulin resistance', 'type': 'Disease', 'start': 687, 'end': 705, 'mesh': 'D007333'}, {'text': 'VPA', 'type': 'Chemical', 'start': 736, 'end': 739, 'mesh': 'D014635'}, {'text': 'NAFLD', 'type': 'Disease', 'start': 786, 'end': 791, 'mesh': 'D065626'}, {'text': 'VPA', 'type': 'Chemical', 'start': 830, 'end': 833, 'mesh': 'D014635'}]"
+1463,19263707,Carbimazole induced ANCA positive vasculitis.,"Anti-thyroid drugs, like carbimazole and propylthiouracil (PTU) are commonly prescribed for the treatment of hyperthyroidism. One should be aware of the side effects of antithyroid medications. Antineutrophil cytoplasmic antibody (ANCA)--associated vasculitis is a potentially life-threatening adverse effect of antithyroidmedications. We report a patient with Graves' disease who developed ANCA positive carbimazole induced vasculitis. The episode was characterized by a vasculitic skin rash associated with large joint arthritis, pyrexia and parotiditis but no renal or pulmonary involvement. He was referred to us for neurological evaluation because he had difficulty in getting up from squatting position and was suspected to have myositis. Carbimazole and methimazole have a lower incidence of reported ANCA positive side effects than PUT. To the best of our knowledge this is the first ANCA positive carbimazole induced vasculitis case reported from India.","[{'text': 'Carbimazole', 'type': 'Chemical', 'start': 0, 'end': 11, 'mesh': 'D002231'}, {'text': 'ANCA positive vasculitis', 'type': 'Disease', 'start': 20, 'end': 44, 'mesh': 'D056648'}, {'text': 'Anti-thyroid drugs', 'type': 'Chemical', 'start': 46, 'end': 64, 'mesh': 'D013956'}, {'text': 'carbimazole', 'type': 'Chemical', 'start': 71, 'end': 82, 'mesh': 'D002231'}, {'text': 'propylthiouracil', 'type': 'Chemical', 'start': 87, 'end': 103, 'mesh': 'D011441'}, {'text': 'PTU', 'type': 'Chemical', 'start': 105, 'end': 108, 'mesh': 'D011441'}, {'text': 'hyperthyroidism', 'type': 'Disease', 'start': 155, 'end': 170, 'mesh': 'D006980'}, {'text': 'antithyroid medications', 'type': 'Chemical', 'start': 215, 'end': 238, 'mesh': 'D013956'}, {'text': 'Antineutrophil cytoplasmic antibody (ANCA)--associated vasculitis', 'type': 'Disease', 'start': 240, 'end': 305, 'mesh': 'D056648'}, {'text': 'antithyroidmedications', 'type': 'Chemical', 'start': 358, 'end': 380, 'mesh': 'D013956'}, {'text': ""Graves' disease"", 'type': 'Disease', 'start': 407, 'end': 422, 'mesh': 'D006111'}, {'text': 'carbimazole', 'type': 'Chemical', 'start': 451, 'end': 462, 'mesh': 'D002231'}, {'text': 'vasculitis', 'type': 'Disease', 'start': 471, 'end': 481, 'mesh': 'D014657'}, {'text': 'vasculitic', 'type': 'Disease', 'start': 518, 'end': 528, 'mesh': 'D014657'}, {'text': 'skin rash', 'type': 'Disease', 'start': 529, 'end': 538, 'mesh': 'D005076'}, {'text': 'arthritis', 'type': 'Disease', 'start': 567, 'end': 576, 'mesh': 'D001168'}, {'text': 'pyrexia', 'type': 'Disease', 'start': 578, 'end': 585, 'mesh': 'D005334'}, {'text': 'parotiditis', 'type': 'Disease', 'start': 590, 'end': 601, 'mesh': 'D010309'}, {'text': 'myositis', 'type': 'Disease', 'start': 781, 'end': 789, 'mesh': 'D009220'}, {'text': 'Carbimazole', 'type': 'Chemical', 'start': 791, 'end': 802, 'mesh': 'D002231'}, {'text': 'methimazole', 'type': 'Chemical', 'start': 807, 'end': 818, 'mesh': 'D008713'}, {'text': 'carbimazole', 'type': 'Chemical', 'start': 952, 'end': 963, 'mesh': 'D002231'}, {'text': 'vasculitis', 'type': 'Disease', 'start': 972, 'end': 982, 'mesh': 'D014657'}]"
+1464,19293073,Aspirin for the primary prevention of cardiovascular events: an update of the evidence for the U.S. Preventive Services Task Force.,"BACKGROUND: Coronary heart disease and cerebrovascular disease are leading causes of death in the United States. In 2002, the U.S. Preventive Services Task Force (USPSTF) strongly recommended that clinicians discuss aspirin with adults who are at increased risk for coronary heart disease. PURPOSE: To determine the benefits and harms of taking aspirin for the primary prevention of myocardial infarctions, strokes, and death. DATA SOURCES: MEDLINE and Cochrane Library (search dates, 1 January 2001 to 28 August 2008), recent systematic reviews, reference lists of retrieved articles, and suggestions from experts. STUDY SELECTION: English-language randomized, controlled trials (RCTs); case-control studies; meta-analyses; and systematic reviews of aspirin versus control for the primary prevention of cardiovascular disease (CVD) were selected to answer the following questions: Does aspirin decrease coronary heart events, strokes, death from coronary heart events or stroke, or all-cause mortality in adults without known CVD? Does aspirin increase gastrointestinal bleeding or hemorrhagic strokes? DATA EXTRACTION: All studies were reviewed, abstracted, and rated for quality by using predefined USPSTF criteria. DATA SYNTHESIS: New evidence from 1 good-quality RCT, 1 good-quality meta-analysis, and 2 fair-quality subanalyses of RCTs demonstrates that aspirin use reduces the number of CVD events in patients without known CVD. Men in these studies experienced fewer myocardial infarctions and women experienced fewer ischemic strokes. Aspirin does not seem to affect CVD mortality or all-cause mortality in either men or women. The use of aspirin for primary prevention increases the risk for major bleeding events, primarily gastrointestinal bleeding events, in both men and women. Men have an increased risk for hemorrhagic strokes with aspirin use. A new RCT and meta-analysis suggest that the risk for hemorrhagic strokes in women is not statistically significantly increased. LIMITATIONS: New evidence on aspirin for the primary prevention of CVD is limited. The dose of aspirin used in the RCTs varied, which prevented the estimation of the most appropriate dose for primary prevention. Several of the RCTs were conducted within populations of health professionals, which potentially limits generalizability. CONCLUSION: Aspirin reduces the risk for myocardial infarction in men and strokes in women. Aspirin use increases the risk for serious bleeding events.","[{'text': 'Aspirin', 'type': 'Chemical', 'start': 0, 'end': 7, 'mesh': 'D001241'}, {'text': 'Coronary heart disease', 'type': 'Disease', 'start': 144, 'end': 166, 'mesh': 'D003327'}, {'text': 'cerebrovascular disease', 'type': 'Disease', 'start': 171, 'end': 194, 'mesh': 'D002561'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 348, 'end': 355, 'mesh': 'D001241'}, {'text': 'coronary heart disease', 'type': 'Disease', 'start': 398, 'end': 420, 'mesh': 'D003327'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 477, 'end': 484, 'mesh': 'D001241'}, {'text': 'myocardial infarctions', 'type': 'Disease', 'start': 515, 'end': 537, 'mesh': 'D009203'}, {'text': 'strokes', 'type': 'Disease', 'start': 539, 'end': 546, 'mesh': 'D020521'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 883, 'end': 890, 'mesh': 'D001241'}, {'text': 'cardiovascular disease', 'type': 'Disease', 'start': 936, 'end': 958, 'mesh': 'D002318'}, {'text': 'CVD', 'type': 'Disease', 'start': 960, 'end': 963, 'mesh': 'D002318'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1019, 'end': 1026, 'mesh': 'D001241'}, {'text': 'strokes', 'type': 'Disease', 'start': 1059, 'end': 1066, 'mesh': 'D020521'}, {'text': 'stroke', 'type': 'Disease', 'start': 1104, 'end': 1110, 'mesh': 'D020521'}, {'text': 'CVD', 'type': 'Disease', 'start': 1159, 'end': 1162, 'mesh': 'D002318'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1169, 'end': 1176, 'mesh': 'D001241'}, {'text': 'gastrointestinal bleeding', 'type': 'Disease', 'start': 1186, 'end': 1211, 'mesh': 'D006471'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1492, 'end': 1499, 'mesh': 'D001241'}, {'text': 'CVD', 'type': 'Disease', 'start': 1526, 'end': 1529, 'mesh': 'D002318'}, {'text': 'CVD', 'type': 'Disease', 'start': 1563, 'end': 1566, 'mesh': 'D002318'}, {'text': 'myocardial infarctions', 'type': 'Disease', 'start': 1607, 'end': 1629, 'mesh': 'D009203'}, {'text': 'strokes', 'type': 'Disease', 'start': 1667, 'end': 1674, 'mesh': 'D020521'}, {'text': 'Aspirin', 'type': 'Chemical', 'start': 1676, 'end': 1683, 'mesh': 'D001241'}, {'text': 'CVD', 'type': 'Disease', 'start': 1708, 'end': 1711, 'mesh': 'D002318'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1780, 'end': 1787, 'mesh': 'D001241'}, {'text': 'bleeding', 'type': 'Disease', 'start': 1840, 'end': 1848, 'mesh': 'D006470'}, {'text': 'gastrointestinal bleeding', 'type': 'Disease', 'start': 1867, 'end': 1892, 'mesh': 'D006471'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 1980, 'end': 1987, 'mesh': 'D001241'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 2151, 'end': 2158, 'mesh': 'D001241'}, {'text': 'CVD', 'type': 'Disease', 'start': 2189, 'end': 2192, 'mesh': 'D002318'}, {'text': 'aspirin', 'type': 'Chemical', 'start': 2217, 'end': 2224, 'mesh': 'D001241'}, {'text': 'Aspirin', 'type': 'Chemical', 'start': 2468, 'end': 2475, 'mesh': 'D001241'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 2497, 'end': 2518, 'mesh': 'D009203'}, {'text': 'strokes', 'type': 'Disease', 'start': 2530, 'end': 2537, 'mesh': 'D020521'}, {'text': 'Aspirin', 'type': 'Chemical', 'start': 2548, 'end': 2555, 'mesh': 'D001241'}, {'text': 'bleeding', 'type': 'Disease', 'start': 2591, 'end': 2599, 'mesh': 'D006470'}]"
+1465,19338378,Reducing harm associated with anticoagulation: practical considerations of argatroban therapy in heparin-induced thrombocytopenia.,"Argatroban is a hepatically metabolized, direct thrombin inhibitor used for prophylaxis or treatment of thrombosis in heparin-induced thrombocytopenia (HIT) and for patients with or at risk of HIT undergoing percutaneous coronary intervention (PCI). The objective of this review is to summarize practical considerations of argatroban therapy in HIT. The US FDA-recommended argatroban dose in HIT is 2 microg/kg/min (reduced in patients with hepatic impairment and in paediatric patients), adjusted to achieve activated partial thromboplastin times (aPTTs) 1.5-3 times baseline (not >100 seconds). Contemporary experiences indicate that reduced doses are also needed in patients with conditions associated with hepatic hypoperfusion, e.g. heart failure, yet are unnecessary for renal dysfunction, adult age, sex, race/ethnicity or obesity. Argatroban 0.5-1.2 microg/kg/min typically supports therapeutic aPTTs. The FDA-recommended dose during PCI is 25 microg/kg/min (350 microg/kg initial bolus), adjusted to achieve activated clotting times (ACTs) of 300-450 sec. For PCI, argatroban has not been investigated in hepatically impaired patients; dose adjustment is unnecessary for adult age, sex, race/ethnicity or obesity, and lesser doses may be adequate with concurrent glycoprotein IIb/IIIa inhibition. Argatroban prolongs the International Normalized Ratio, and published approaches for monitoring the argatroban-to-warfarin transition should be followed. Major bleeding with argatroban is 0-10% in the non-interventional setting and 0-5.8% periprocedurally. Argatroban has no specific antidote, and if excessive anticoagulation occurs, argatroban infusion should be stopped or reduced. Improved familiarity of healthcare professionals with argatroban therapy in HIT, including in special populations and during PCI, may facilitate reduction of harm associated with HIT (e.g. fewer thromboses) or its treatment (e.g. fewer argatroban medication errors).","[{'text': 'argatroban', 'type': 'Chemical', 'start': 75, 'end': 85, 'mesh': 'C031942'}, {'text': 'heparin', 'type': 'Chemical', 'start': 97, 'end': 104, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 113, 'end': 129, 'mesh': 'D013921'}, {'text': 'Argatroban', 'type': 'Chemical', 'start': 131, 'end': 141, 'mesh': 'C031942'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 235, 'end': 245, 'mesh': 'D013927'}, {'text': 'heparin', 'type': 'Chemical', 'start': 249, 'end': 256, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 265, 'end': 281, 'mesh': 'D013921'}, {'text': 'HIT', 'type': 'Disease', 'start': 283, 'end': 286, 'mesh': 'D013921'}, {'text': 'HIT', 'type': 'Disease', 'start': 324, 'end': 327, 'mesh': 'D013921'}, {'text': 'argatroban', 'type': 'Chemical', 'start': 454, 'end': 464, 'mesh': 'C031942'}, {'text': 'HIT', 'type': 'Disease', 'start': 476, 'end': 479, 'mesh': 'D013921'}, {'text': 'argatroban', 'type': 'Chemical', 'start': 504, 'end': 514, 'mesh': 'C031942'}, {'text': 'HIT', 'type': 'Disease', 'start': 523, 'end': 526, 'mesh': 'D013921'}, {'text': 'hepatic impairment', 'type': 'Disease', 'start': 572, 'end': 590, 'mesh': 'D008107'}, {'text': 'heart failure', 'type': 'Disease', 'start': 869, 'end': 882, 'mesh': 'D006333'}, {'text': 'renal dysfunction', 'type': 'Disease', 'start': 908, 'end': 925, 'mesh': 'D007674'}, {'text': 'obesity', 'type': 'Disease', 'start': 961, 'end': 968, 'mesh': 'D009765'}, {'text': 'Argatroban', 'type': 'Chemical', 'start': 970, 'end': 980, 'mesh': 'C031942'}, {'text': 'argatroban', 'type': 'Chemical', 'start': 1205, 'end': 1215, 'mesh': 'C031942'}, {'text': 'obesity', 'type': 'Disease', 'start': 1345, 'end': 1352, 'mesh': 'D009765'}, {'text': 'Argatroban', 'type': 'Chemical', 'start': 1437, 'end': 1447, 'mesh': 'C031942'}, {'text': 'argatroban', 'type': 'Chemical', 'start': 1537, 'end': 1547, 'mesh': 'C031942'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 1551, 'end': 1559, 'mesh': 'D014859'}, {'text': 'bleeding', 'type': 'Disease', 'start': 1597, 'end': 1605, 'mesh': 'D006470'}, {'text': 'argatroban', 'type': 'Chemical', 'start': 1611, 'end': 1621, 'mesh': 'C031942'}, {'text': 'Argatroban', 'type': 'Chemical', 'start': 1694, 'end': 1704, 'mesh': 'C031942'}, {'text': 'argatroban', 'type': 'Chemical', 'start': 1772, 'end': 1782, 'mesh': 'C031942'}, {'text': 'argatroban', 'type': 'Chemical', 'start': 1876, 'end': 1886, 'mesh': 'C031942'}, {'text': 'HIT', 'type': 'Disease', 'start': 1898, 'end': 1901, 'mesh': 'D013921'}, {'text': 'HIT', 'type': 'Disease', 'start': 2001, 'end': 2004, 'mesh': 'D013921'}, {'text': 'argatroban', 'type': 'Chemical', 'start': 2058, 'end': 2068, 'mesh': 'C031942'}]"
+1466,19392810,Rhabdomyolysis and brain ischemic stroke in a heroin-dependent male under methadone maintenance therapy.,"OBJECTIVE: There are several complications associated with heroin abuse, some of which are life-threatening. Methadone may aggravate this problem. METHOD: A clinical case description. RESULTS: A 33-year-old man presented with rhabdomyolysis and cerebral ischemic stroke after intravenous heroin. He had used heroin since age 20, and had used 150 mg methadone daily for 6 months. He was found unconsciousness at home and was sent to our hospital. In the ER, his opiate level was 4497 ng/ml. In the ICU, we found rhabdomyolysis, acute renal failure and acute respiratory failure. After transfer to an internal ward, we noted aphasia and weakness of his left limbs. After MRI, we found cerebral ischemic infarction. CONCLUSION: Those using methadone and heroin simultaneously may increase risk of rhabdomyolysis and ischemic stroke. Patients under methadone maintenance therapy should be warned regarding these serious adverse events. Hypotheses of heroin-related rhabdomyolysis and stroke in heroin abusers are discussed.","[{'text': 'Rhabdomyolysis', 'type': 'Disease', 'start': 0, 'end': 14, 'mesh': 'D012206'}, {'text': 'ischemic stroke', 'type': 'Disease', 'start': 25, 'end': 40, 'mesh': 'D002544'}, {'text': 'heroin', 'type': 'Chemical', 'start': 46, 'end': 52, 'mesh': 'D003932'}, {'text': 'methadone', 'type': 'Chemical', 'start': 74, 'end': 83, 'mesh': 'D008691'}, {'text': 'heroin abuse', 'type': 'Disease', 'start': 164, 'end': 176, 'mesh': 'D006556'}, {'text': 'Methadone', 'type': 'Chemical', 'start': 214, 'end': 223, 'mesh': 'D008691'}, {'text': 'rhabdomyolysis', 'type': 'Disease', 'start': 331, 'end': 345, 'mesh': 'D012206'}, {'text': 'ischemic stroke', 'type': 'Disease', 'start': 359, 'end': 374, 'mesh': 'D002544'}, {'text': 'heroin', 'type': 'Chemical', 'start': 393, 'end': 399, 'mesh': 'D003932'}, {'text': 'heroin', 'type': 'Chemical', 'start': 413, 'end': 419, 'mesh': 'D003932'}, {'text': 'methadone', 'type': 'Chemical', 'start': 454, 'end': 463, 'mesh': 'D008691'}, {'text': 'unconsciousness', 'type': 'Disease', 'start': 497, 'end': 512, 'mesh': 'D014474'}, {'text': 'rhabdomyolysis', 'type': 'Disease', 'start': 616, 'end': 630, 'mesh': 'D012206'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 632, 'end': 651, 'mesh': 'D058186'}, {'text': 'respiratory failure', 'type': 'Disease', 'start': 662, 'end': 681, 'mesh': 'D012131'}, {'text': 'aphasia', 'type': 'Disease', 'start': 728, 'end': 735, 'mesh': 'D001037'}, {'text': 'weakness', 'type': 'Disease', 'start': 740, 'end': 748, 'mesh': 'D018908'}, {'text': 'cerebral ischemic infarction', 'type': 'Disease', 'start': 788, 'end': 816, 'mesh': 'D002544'}, {'text': 'methadone', 'type': 'Chemical', 'start': 842, 'end': 851, 'mesh': 'D008691'}, {'text': 'heroin', 'type': 'Chemical', 'start': 856, 'end': 862, 'mesh': 'D003932'}, {'text': 'rhabdomyolysis', 'type': 'Disease', 'start': 899, 'end': 913, 'mesh': 'D012206'}, {'text': 'ischemic stroke', 'type': 'Disease', 'start': 918, 'end': 933, 'mesh': 'D002544'}, {'text': 'methadone', 'type': 'Chemical', 'start': 950, 'end': 959, 'mesh': 'D008691'}, {'text': 'heroin', 'type': 'Chemical', 'start': 1051, 'end': 1057, 'mesh': 'D003932'}, {'text': 'rhabdomyolysis', 'type': 'Disease', 'start': 1066, 'end': 1080, 'mesh': 'D012206'}, {'text': 'stroke', 'type': 'Disease', 'start': 1085, 'end': 1091, 'mesh': 'D020521'}, {'text': 'heroin', 'type': 'Chemical', 'start': 1095, 'end': 1101, 'mesh': 'D003932'}]"
+1467,19419794,Increased vulnerability to 6-hydroxydopamine lesion and reduced development of dyskinesias in mice lacking CB1 cannabinoid receptors.,"Motor impairment, dopamine (DA) neuronal activity and proenkephalin (PENK) gene expression in the caudate-putamen (CPu) were measured in 6-OHDA-lesioned and treated (L-DOPA+benserazide) CB1 KO and WT mice. A lesion induced by 6-OHDA produced more severe motor deterioration in CB1 KO mice accompanied by more loss of DA neurons and increased PENK gene expression in the CPu. Oxidative/nitrosative and neuroinflammatory parameters were estimated in the CPu and cingulate cortex (Cg). CB1 KO mice exhibited higher MDA levels and iNOS protein expression in the CPu and Cg compared to WT mice. Treatment with L-DOPA+benserazide (12 weeks) resulted in less severe dyskinesias in CB1 KO than in WT mice. The results revealed that the lack of cannabinoid CB1 receptors increased the severity of motor impairment and DA lesion, and reduced L-DOPA-induced dyskinesias. These results suggest that activation of CB1 receptors offers neuroprotection against dopaminergic lesion and the development of L-DOPA-induced dyskinesias.","[{'text': '6-hydroxydopamine', 'type': 'Chemical', 'start': 27, 'end': 44, 'mesh': 'D016627'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 79, 'end': 90, 'mesh': 'D004409'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 152, 'end': 160, 'mesh': 'D004298'}, {'text': 'DA', 'type': 'Chemical', 'start': 162, 'end': 164, 'mesh': 'D004298'}, {'text': 'proenkephalin', 'type': 'Chemical', 'start': 188, 'end': 201, 'mesh': 'C029992'}, {'text': 'PENK', 'type': 'Chemical', 'start': 203, 'end': 207, 'mesh': 'C029992'}, {'text': '6-OHDA', 'type': 'Chemical', 'start': 271, 'end': 277, 'mesh': 'D016627'}, {'text': 'L-DOPA+benserazide', 'type': 'Chemical', 'start': 300, 'end': 318, 'mesh': 'C005177'}, {'text': '6-OHDA', 'type': 'Chemical', 'start': 360, 'end': 366, 'mesh': 'D016627'}, {'text': 'DA', 'type': 'Chemical', 'start': 451, 'end': 453, 'mesh': 'D004298'}, {'text': 'PENK', 'type': 'Chemical', 'start': 476, 'end': 480, 'mesh': 'C029992'}, {'text': 'MDA', 'type': 'Chemical', 'start': 646, 'end': 649, 'mesh': 'D008315'}, {'text': 'L-DOPA+benserazide', 'type': 'Chemical', 'start': 739, 'end': 757, 'mesh': 'C005177'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 793, 'end': 804, 'mesh': 'D004409'}, {'text': 'DA', 'type': 'Chemical', 'start': 943, 'end': 945, 'mesh': 'D004298'}, {'text': 'L-DOPA', 'type': 'Chemical', 'start': 966, 'end': 972, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 981, 'end': 992, 'mesh': 'D004409'}, {'text': 'L-DOPA', 'type': 'Chemical', 'start': 1123, 'end': 1129, 'mesh': 'D007980'}, {'text': 'dyskinesias', 'type': 'Disease', 'start': 1138, 'end': 1149, 'mesh': 'D004409'}]"
+1468,19447152,Animal model of mania induced by ouabain: Evidence of oxidative stress in submitochondrial particles of the rat brain.,"The intracerebroventricular (ICV) administration of ouabain (a Na(+)/K(+)-ATPase inhibitor) in rats has been suggested to mimic some symptoms of human bipolar mania. Clinical studies have shown that bipolar disorder may be related to mitochondrial dysfunction. Herein, we investigated the behavioral and biochemical effects induced by the ICV administration of ouabain in rats. To achieve this aim, the effects of ouabain injection immediately after and 7 days following a single ICV administration (at concentrations of 10(-2) and 10(-3)M) on locomotion was measured using the open-field test. Additionally, thiobarbituric acid reactive substances (TBARSs) and superoxide production were measured in submitochondrial particles of the prefrontal cortex, hippocampus, striatum and amygdala. Our findings demonstrated that ouabain at 10(-2) and 10(-3)M induced hyperlocomotion in rats, and this response remained up to 7 days following a single ICV injection. In addition, we observed that the persistent increase in the rat spontaneous locomotion is associated with increased TBARS levels and superoxide generation in submitochondrial particles in the prefrontal cortex, striatum and amygdala. In conclusion, ouabain-induced mania-like behavior may provide a useful animal model to test the hypothesis of the involvement of oxidative stress in bipolar disorder.","[{'text': 'mania', 'type': 'Disease', 'start': 16, 'end': 21, 'mesh': 'D001714'}, {'text': 'ouabain', 'type': 'Chemical', 'start': 33, 'end': 40, 'mesh': 'D010042'}, {'text': 'ouabain', 'type': 'Chemical', 'start': 171, 'end': 178, 'mesh': 'D010042'}, {'text': 'Na', 'type': 'Chemical', 'start': 182, 'end': 184, 'mesh': 'D012964'}, {'text': 'K', 'type': 'Chemical', 'start': 188, 'end': 189, 'mesh': 'D011188'}, {'text': 'bipolar mania', 'type': 'Disease', 'start': 270, 'end': 283, 'mesh': 'D001714'}, {'text': 'bipolar disorder', 'type': 'Disease', 'start': 318, 'end': 334, 'mesh': 'D001714'}, {'text': 'mitochondrial dysfunction', 'type': 'Disease', 'start': 353, 'end': 378, 'mesh': 'D028361'}, {'text': 'ouabain', 'type': 'Chemical', 'start': 480, 'end': 487, 'mesh': 'D010042'}, {'text': 'ouabain', 'type': 'Chemical', 'start': 533, 'end': 540, 'mesh': 'D010042'}, {'text': 'thiobarbituric acid', 'type': 'Chemical', 'start': 728, 'end': 747, 'mesh': 'C029684'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 781, 'end': 791, 'mesh': 'D013481'}, {'text': 'ouabain', 'type': 'Chemical', 'start': 940, 'end': 947, 'mesh': 'D010042'}, {'text': 'hyperlocomotion', 'type': 'Disease', 'start': 978, 'end': 993, 'mesh': 'D009069'}, {'text': 'superoxide', 'type': 'Chemical', 'start': 1211, 'end': 1221, 'mesh': 'D013481'}, {'text': 'ouabain', 'type': 'Chemical', 'start': 1327, 'end': 1334, 'mesh': 'D010042'}, {'text': 'mania', 'type': 'Disease', 'start': 1343, 'end': 1348, 'mesh': 'D001714'}, {'text': 'bipolar disorder', 'type': 'Disease', 'start': 1462, 'end': 1478, 'mesh': 'D001714'}]"
+1469,19515070,Intraoperative dialysis during liver transplantation with citrate dialysate.,"Liver transplantation for acutely ill patients with fulminant liver failure carries high intraoperative and immediate postoperative risks. These are increased with the presence of concomitant acute kidney injury (AKI) and intraoperative dialysis is sometimes required to allow the transplant to proceed. The derangements in the procoagulant and anticoagulant pathways during fulminant liver failure can lead to difficulties with anticoagulation during dialysis, especially when continued in the operating room. Systemic anticoagulation is unsafe and regional citrate anticoagulation in the absence of a functional liver carries the risk of citrate toxicity. Citrate dialysate, a new dialysate with citric acid can be used for anticoagulation in patients who cannot tolerate heparin or regional citrate. We report a case of a 40-year-old female with acetaminophen-induced fulminant liver failure with associated AKI who underwent intraoperative dialytic support during liver transplantation anticoagulated with citrate dialysate during the entire procedure. The patient tolerated the procedure well without any signs of citrate toxicity and maintained adequate anticoagulation for patency of the dialysis circuit. Citrate dialysate is a safe alternative for intradialytic support of liver transplantation in fulminant liver failure.","[{'text': 'citrate', 'type': 'Chemical', 'start': 58, 'end': 65, 'mesh': 'D019343'}, {'text': 'fulminant liver failure', 'type': 'Disease', 'start': 129, 'end': 152, 'mesh': 'D017114'}, {'text': 'acute kidney injury', 'type': 'Disease', 'start': 269, 'end': 288, 'mesh': 'D058186'}, {'text': 'AKI', 'type': 'Disease', 'start': 290, 'end': 293, 'mesh': 'D058186'}, {'text': 'fulminant liver failure', 'type': 'Disease', 'start': 452, 'end': 475, 'mesh': 'D017114'}, {'text': 'citrate', 'type': 'Chemical', 'start': 636, 'end': 643, 'mesh': 'D019343'}, {'text': 'citrate', 'type': 'Chemical', 'start': 717, 'end': 724, 'mesh': 'D019343'}, {'text': 'toxicity', 'type': 'Disease', 'start': 725, 'end': 733, 'mesh': 'D064420'}, {'text': 'Citrate', 'type': 'Chemical', 'start': 735, 'end': 742, 'mesh': 'D019343'}, {'text': 'citric acid', 'type': 'Chemical', 'start': 775, 'end': 786, 'mesh': 'D019343'}, {'text': 'heparin', 'type': 'Chemical', 'start': 851, 'end': 858, 'mesh': 'D006493'}, {'text': 'citrate', 'type': 'Chemical', 'start': 871, 'end': 878, 'mesh': 'D019343'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 926, 'end': 939, 'mesh': 'D000082'}, {'text': 'fulminant liver failure', 'type': 'Disease', 'start': 948, 'end': 971, 'mesh': 'D017114'}, {'text': 'AKI', 'type': 'Disease', 'start': 988, 'end': 991, 'mesh': 'D058186'}, {'text': 'citrate', 'type': 'Chemical', 'start': 1087, 'end': 1094, 'mesh': 'D019343'}, {'text': 'citrate', 'type': 'Chemical', 'start': 1196, 'end': 1203, 'mesh': 'D019343'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1204, 'end': 1212, 'mesh': 'D064420'}, {'text': 'Citrate', 'type': 'Chemical', 'start': 1290, 'end': 1297, 'mesh': 'D019343'}, {'text': 'fulminant liver failure', 'type': 'Disease', 'start': 1384, 'end': 1407, 'mesh': 'D017114'}]"
+1470,19531695,Delirium in a patient with toxic flecainide plasma concentrations: the role of a pharmacokinetic drug interaction with paroxetine.,"OBJECTIVE: To describe a case of flecainide-induced delirium associated with a pharmacokinetic drug interaction with paroxetine. CASE SUMMARY: A 69-year-old white female presented to the emergency department with a history of confusion and paranoia over the past several days. On admission the patient was taking carvedilol 12 mg twice daily, warfarin 2 mg/day, folic acid 1 mg/day, levothyroxine 100 microg/day, pantoprazole 40 mg/day, paroxetine 40 mg/day, and flecainide 100 mg twice daily. Flecainide had been started 2 weeks prior for atrial fibrillation. Laboratory test findings on admission were notable only for a flecainide plasma concentration of 1360 microg/L (reference range 200-1000). A metabolic drug interaction between flecainide and paroxetine, which the patient had been taking for more than 5 years, was considered. Paroxetine was discontinued and the dose of flecainide was reduced to 50 mg twice daily. Her delirium resolved 3 days later. DISCUSSION: Flecainide and pharmacologically similar agents that interact with sodium channels may cause delirium in susceptible patients. A MEDLINE search (1966-January 2009) revealed one in vivo pharmacokinetic study on the interaction between flecainide, a CYP2D6 substrate, and paroxetine, a CYP2D6 inhibitor, as well as 3 case reports of flecainide-induced delirium. According to the Naranjo probability scale, flecainide was the probable cause of the patient's delirium; the Horn Drug Interaction Probability Scale indicates a possible pharmacokinetic drug interaction between flecainide and paroxetine. CONCLUSIONS: Supratherapeutic flecainide plasma concentrations may cause delirium. Because toxicity may occur when flecainide is prescribed with paroxetine and other potent CYP2D6 inhibitors, flecainide plasma concentrations should be monitored closely with commencement of CYP2D6 inhibitors.","[{'text': 'Delirium', 'type': 'Disease', 'start': 0, 'end': 8, 'mesh': 'D003693'}, {'text': 'flecainide', 'type': 'Chemical', 'start': 33, 'end': 43, 'mesh': 'D005424'}, {'text': 'paroxetine', 'type': 'Chemical', 'start': 119, 'end': 129, 'mesh': 'D017374'}, {'text': 'flecainide', 'type': 'Chemical', 'start': 164, 'end': 174, 'mesh': 'D005424'}, {'text': 'delirium', 'type': 'Disease', 'start': 183, 'end': 191, 'mesh': 'D003693'}, {'text': 'paroxetine', 'type': 'Chemical', 'start': 248, 'end': 258, 'mesh': 'D017374'}, {'text': 'confusion', 'type': 'Disease', 'start': 357, 'end': 366, 'mesh': 'D003221'}, {'text': 'paranoia', 'type': 'Disease', 'start': 371, 'end': 379, 'mesh': 'D010259'}, {'text': 'carvedilol', 'type': 'Chemical', 'start': 444, 'end': 454, 'mesh': 'C043211'}, {'text': 'warfarin', 'type': 'Chemical', 'start': 474, 'end': 482, 'mesh': 'D014859'}, {'text': 'folic acid', 'type': 'Chemical', 'start': 493, 'end': 503, 'mesh': 'D005492'}, {'text': 'levothyroxine', 'type': 'Chemical', 'start': 514, 'end': 527, 'mesh': 'D013974'}, {'text': 'pantoprazole', 'type': 'Chemical', 'start': 544, 'end': 556, 'mesh': 'C064276'}, {'text': 'paroxetine', 'type': 'Chemical', 'start': 568, 'end': 578, 'mesh': 'D017374'}, {'text': 'flecainide', 'type': 'Chemical', 'start': 594, 'end': 604, 'mesh': 'D005424'}, {'text': 'Flecainide', 'type': 'Chemical', 'start': 625, 'end': 635, 'mesh': 'D005424'}, {'text': 'atrial fibrillation', 'type': 'Disease', 'start': 671, 'end': 690, 'mesh': 'D001281'}, {'text': 'flecainide', 'type': 'Chemical', 'start': 754, 'end': 764, 'mesh': 'D005424'}, {'text': 'flecainide', 'type': 'Chemical', 'start': 868, 'end': 878, 'mesh': 'D005424'}, {'text': 'paroxetine', 'type': 'Chemical', 'start': 883, 'end': 893, 'mesh': 'D017374'}, {'text': 'Paroxetine', 'type': 'Chemical', 'start': 968, 'end': 978, 'mesh': 'D017374'}, {'text': 'flecainide', 'type': 'Chemical', 'start': 1012, 'end': 1022, 'mesh': 'D005424'}, {'text': 'delirium', 'type': 'Disease', 'start': 1061, 'end': 1069, 'mesh': 'D003693'}, {'text': 'Flecainide', 'type': 'Chemical', 'start': 1105, 'end': 1115, 'mesh': 'D005424'}, {'text': 'sodium', 'type': 'Chemical', 'start': 1172, 'end': 1178, 'mesh': 'D012964'}, {'text': 'delirium', 'type': 'Disease', 'start': 1198, 'end': 1206, 'mesh': 'D003693'}, {'text': 'flecainide', 'type': 'Chemical', 'start': 1339, 'end': 1349, 'mesh': 'D005424'}, {'text': 'paroxetine', 'type': 'Chemical', 'start': 1375, 'end': 1385, 'mesh': 'D017374'}, {'text': 'flecainide', 'type': 'Chemical', 'start': 1436, 'end': 1446, 'mesh': 'D005424'}, {'text': 'delirium', 'type': 'Disease', 'start': 1455, 'end': 1463, 'mesh': 'D003693'}, {'text': 'flecainide', 'type': 'Chemical', 'start': 1509, 'end': 1519, 'mesh': 'D005424'}, {'text': 'delirium', 'type': 'Disease', 'start': 1560, 'end': 1568, 'mesh': 'D003693'}, {'text': 'flecainide', 'type': 'Chemical', 'start': 1676, 'end': 1686, 'mesh': 'D005424'}, {'text': 'paroxetine', 'type': 'Chemical', 'start': 1691, 'end': 1701, 'mesh': 'D017374'}, {'text': 'flecainide', 'type': 'Chemical', 'start': 1733, 'end': 1743, 'mesh': 'D005424'}, {'text': 'delirium', 'type': 'Disease', 'start': 1776, 'end': 1784, 'mesh': 'D003693'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1794, 'end': 1802, 'mesh': 'D064420'}, {'text': 'flecainide', 'type': 'Chemical', 'start': 1818, 'end': 1828, 'mesh': 'D005424'}, {'text': 'paroxetine', 'type': 'Chemical', 'start': 1848, 'end': 1858, 'mesh': 'D017374'}, {'text': 'flecainide', 'type': 'Chemical', 'start': 1895, 'end': 1905, 'mesh': 'D005424'}]"
+1471,19549709,Efficacy of everolimus (RAD001) in patients with advanced NSCLC previously treated with chemotherapy alone or with chemotherapy and EGFR inhibitors.,"BACKGROUND: Treatment options are scarce in pretreated advanced non-small-cell lung cancer (NSCLC) patients. RAD001, an oral inhibitor of the mammalian target of rapamycin (mTOR), has shown phase I efficacy in NSCLC. METHODS: Stage IIIb or IV NSCLC patients, with two or fewer prior chemotherapy regimens, one platinum based (stratum 1) or both chemotherapy and epidermal growth factor receptor tyrosine kinase inhibitors (stratum 2), received RAD001 10 mg/day until progression or unacceptable toxicity. Primary objective was overall response rate (ORR). Analyses of markers associated with the mTOR pathway were carried out on archival tumor from a subgroup using immunohistochemistry (IHC) and direct mutation sequencing. RESULTS: Eighty-five patients were enrolled, 42 in stratum 1 and 43 in stratum. ORR was 4.7% (7.1% stratum 1; 2.3% stratum 2). Overall disease control rate was 47.1%. Median progression-free survivals (PFSs) were 2.6 (stratum 1) and 2.7 months (stratum 2). Common > or =grade 3 events were fatigue, dyspnea, stomatitis, anemia, and thrombocytopenia. Pneumonitis, probably or possibly related, mainly grade 1/2, occurred in 25%. Cox regression analysis of IHC scores found that only phospho AKT (pAKT) was a significant independent predictor of worse PFS. CONCLUSIONS: RAD001 10 mg/day was well tolerated, showing modest clinical activity in pretreated NSCLC. Evaluation of RAD001 plus standard therapy for metastatic NSCLC continues.","[{'text': 'everolimus', 'type': 'Chemical', 'start': 12, 'end': 22, 'mesh': 'C107135'}, {'text': 'RAD001', 'type': 'Chemical', 'start': 24, 'end': 30, 'mesh': 'C107135'}, {'text': 'NSCLC', 'type': 'Disease', 'start': 58, 'end': 63, 'mesh': 'D002289'}, {'text': 'non-small-cell lung cancer', 'type': 'Disease', 'start': 213, 'end': 239, 'mesh': 'D002289'}, {'text': 'NSCLC', 'type': 'Disease', 'start': 241, 'end': 246, 'mesh': 'D002289'}, {'text': 'RAD001', 'type': 'Chemical', 'start': 258, 'end': 264, 'mesh': 'C107135'}, {'text': 'rapamycin', 'type': 'Chemical', 'start': 311, 'end': 320, 'mesh': 'D020123'}, {'text': 'NSCLC', 'type': 'Disease', 'start': 359, 'end': 364, 'mesh': 'D002289'}, {'text': 'NSCLC', 'type': 'Disease', 'start': 392, 'end': 397, 'mesh': 'D002289'}, {'text': 'platinum', 'type': 'Chemical', 'start': 459, 'end': 467, 'mesh': 'D010984'}, {'text': 'tyrosine', 'type': 'Chemical', 'start': 544, 'end': 552, 'mesh': 'D014443'}, {'text': 'RAD001', 'type': 'Chemical', 'start': 593, 'end': 599, 'mesh': 'C107135'}, {'text': 'toxicity', 'type': 'Disease', 'start': 644, 'end': 652, 'mesh': 'D064420'}, {'text': 'tumor', 'type': 'Disease', 'start': 787, 'end': 792, 'mesh': 'D009369'}, {'text': 'fatigue', 'type': 'Disease', 'start': 1164, 'end': 1171, 'mesh': 'D005221'}, {'text': 'dyspnea', 'type': 'Disease', 'start': 1173, 'end': 1180, 'mesh': 'D004417'}, {'text': 'stomatitis', 'type': 'Disease', 'start': 1182, 'end': 1192, 'mesh': 'D013280'}, {'text': 'anemia', 'type': 'Disease', 'start': 1194, 'end': 1200, 'mesh': 'D000740'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 1206, 'end': 1222, 'mesh': 'D013921'}, {'text': 'Pneumonitis', 'type': 'Disease', 'start': 1224, 'end': 1235, 'mesh': 'D011014'}, {'text': 'RAD001', 'type': 'Chemical', 'start': 1442, 'end': 1448, 'mesh': 'C107135'}, {'text': 'NSCLC', 'type': 'Disease', 'start': 1526, 'end': 1531, 'mesh': 'D002289'}, {'text': 'RAD001', 'type': 'Chemical', 'start': 1547, 'end': 1553, 'mesh': 'C107135'}, {'text': 'NSCLC', 'type': 'Disease', 'start': 1591, 'end': 1596, 'mesh': 'D002289'}]"
+1472,19553912,Posttransplant anemia: the role of sirolimus.,"Posttransplant anemia is a common problem that may hinder patients' quality of life. It occurs in 12 to 76% of patients, and is most common in the immediate posttransplant period. A variety of factors have been identified that increase the risk of posttransplant anemia, of which the level of renal function is most important. Sirolimus, a mammalian target of rapamycin inhibitor, has been implicated as playing a special role in posttransplant anemia. This review considers anemia associated with sirolimus, including its presentation, mechanisms, and management.","[{'text': 'anemia', 'type': 'Disease', 'start': 15, 'end': 21, 'mesh': 'D000740'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 35, 'end': 44, 'mesh': 'D020123'}, {'text': 'anemia', 'type': 'Disease', 'start': 61, 'end': 67, 'mesh': 'D000740'}, {'text': 'anemia', 'type': 'Disease', 'start': 309, 'end': 315, 'mesh': 'D000740'}, {'text': 'Sirolimus', 'type': 'Chemical', 'start': 373, 'end': 382, 'mesh': 'D020123'}, {'text': 'rapamycin', 'type': 'Chemical', 'start': 406, 'end': 415, 'mesh': 'D020123'}, {'text': 'anemia', 'type': 'Disease', 'start': 491, 'end': 497, 'mesh': 'D000740'}, {'text': 'anemia', 'type': 'Disease', 'start': 521, 'end': 527, 'mesh': 'D000740'}, {'text': 'sirolimus', 'type': 'Chemical', 'start': 544, 'end': 553, 'mesh': 'D020123'}]"
+1473,19655282,Coronary computerized tomography angiography for rapid discharge of low-risk patients with cocaine-associated chest pain.,"BACKGROUND: Most patients presenting to emergency departments (EDs) with cocaine-associated chest pain are admitted for at least 12 hours and receive a ""rule out acute coronary syndrome"" protocol, often with noninvasive testing prior to discharge. In patients without cocaine use, coronary computerized tomography angiography (CTA) has been shown to be useful for identifying a group of patients at low risk for cardiac events who can be safely discharged. It is unclear whether a coronary CTA strategy would be efficacious in cocaine-associated chest pain, as coronary vasospasm may account for some of the ischemia. We studied whether a negative coronary CTA in patients with cocaine-associated chest pain could identify a subset safe for discharge. METHODS: We prospectively evaluated the safety of coronary CTA for low-risk patients who presented to the ED with cocaineassociated chest pain (self-reported or positive urine test). Consecutive patients received either immediate coronary CTA in the ED (without serial markers) or underwent coronary CTA after a brief observation period with serial cardiac marker measurements. Patients with negative coronary CTA (maximal stenosis less than 50%) were discharged. The main outcome was 30-day cardiovascular death or myocardial infarction. RESULTS: A total of 59 patients with cocaine-associated chest pain were evaluated. Patients had a mean age of 45.6 +/- 6.6 yrs and were 86% black, 66% male. Seventy-nine percent had a normal or nonspecific ECG and 85% had a TIMI score <2. Twenty patients received coronary CTA immediately in the ED, 18 of whom were discharged following CTA (90%). Thirty-nine received coronary CTA after a brief observation period, with 37 discharged home following CTA (95%). Six patients had coronary stenosis >or=50%. During the 30-day follow-up period, no patients died of a cardiovascular event (0%; 95% CI, 0-6.1%) and no patient sustained a nonfatal myocardial infarction (0%; 95% CI, 0-6.1%). CONCLUSIONS: Although cocaine-associated myocardial ischemia can result from coronary vasoconstriction, patients with cocaine associated chest pain, a non-ischemic ECG, and a TIMI risk score <2 may be safely discharged from the ED after a negative coronary CTA with a low risk of 30-day adverse events.","[{'text': 'cocaine', 'type': 'Chemical', 'start': 91, 'end': 98, 'mesh': 'D003042'}, {'text': 'chest pain', 'type': 'Disease', 'start': 110, 'end': 120, 'mesh': 'D002637'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 195, 'end': 202, 'mesh': 'D003042'}, {'text': 'chest pain', 'type': 'Disease', 'start': 214, 'end': 224, 'mesh': 'D002637'}, {'text': 'acute coronary syndrome', 'type': 'Disease', 'start': 284, 'end': 307, 'mesh': 'D054058'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 390, 'end': 397, 'mesh': 'D003042'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 649, 'end': 656, 'mesh': 'D003042'}, {'text': 'chest pain', 'type': 'Disease', 'start': 668, 'end': 678, 'mesh': 'D002637'}, {'text': 'coronary vasospasm', 'type': 'Disease', 'start': 683, 'end': 701, 'mesh': 'D003329'}, {'text': 'ischemia', 'type': 'Disease', 'start': 730, 'end': 738, 'mesh': 'D007511'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 800, 'end': 807, 'mesh': 'D003042'}, {'text': 'chest pain', 'type': 'Disease', 'start': 819, 'end': 829, 'mesh': 'D002637'}, {'text': 'chest pain', 'type': 'Disease', 'start': 1006, 'end': 1016, 'mesh': 'D002637'}, {'text': 'stenosis', 'type': 'Disease', 'start': 1297, 'end': 1305, 'mesh': 'D003251'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 1390, 'end': 1411, 'mesh': 'D009203'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1450, 'end': 1457, 'mesh': 'D003042'}, {'text': 'chest pain', 'type': 'Disease', 'start': 1469, 'end': 1479, 'mesh': 'D002637'}, {'text': 'coronary stenosis', 'type': 'Disease', 'start': 1891, 'end': 1908, 'mesh': 'D023921'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 2054, 'end': 2075, 'mesh': 'D009203'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 2120, 'end': 2127, 'mesh': 'D003042'}, {'text': 'myocardial ischemia', 'type': 'Disease', 'start': 2139, 'end': 2158, 'mesh': 'D017202'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 2216, 'end': 2223, 'mesh': 'D003042'}, {'text': 'chest pain', 'type': 'Disease', 'start': 2235, 'end': 2245, 'mesh': 'D002637'}, {'text': 'ischemic', 'type': 'Disease', 'start': 2253, 'end': 2261, 'mesh': 'D007511'}]"
+1474,19715529,Late fulminant posterior reversible encephalopathy syndrome after liver transplant.,"OBJECTIVES: Posterior leukoencephalopathy due to calcineurin-inhibitor-related neurotoxicity is a rare but severe complication that results from treatment with immunosuppressive agents (primarily those administered after a liver or kidney transplant). The pathophysiologic mechanisms of that disorder remain unknown. CASE: We report the case of a 46-year-old woman who received a liver transplant in our center as treatment for alcoholic cirrhosis and in whom either a fulminant course of posterior leukoencephalopathy or posterior reversible encephalopathy syndrome developed 110 days after transplant. After an initially uneventful course after the transplant, the patient rapidly fell into deep coma. RESULTS: Cerebral MRI scan showed typical signs of enhancement in the pontine and posterior regions. Switching the immunosuppressive regimen from tacrolimus to cyclosporine did not improve the clinical situation. The termination of treatment with any calcineurin inhibitor resulted in a complete resolution of that complication. CONCLUSIONS: Posterior reversible encephalopathy syndrome after liver transplant is rare. We recommend a complete cessation of any calcineurin inhibitor rather than a dose reduction.","[{'text': 'posterior reversible encephalopathy syndrome', 'type': 'Disease', 'start': 15, 'end': 59, 'mesh': 'D054038'}, {'text': 'Posterior leukoencephalopathy', 'type': 'Disease', 'start': 96, 'end': 125, 'mesh': 'D054038'}, {'text': 'neurotoxicity', 'type': 'Disease', 'start': 163, 'end': 176, 'mesh': 'D020258'}, {'text': 'alcoholic cirrhosis', 'type': 'Disease', 'start': 512, 'end': 531, 'mesh': 'D008104'}, {'text': 'posterior leukoencephalopathy', 'type': 'Disease', 'start': 573, 'end': 602, 'mesh': 'D054038'}, {'text': 'posterior reversible encephalopathy syndrome', 'type': 'Disease', 'start': 606, 'end': 650, 'mesh': 'D054038'}, {'text': 'tacrolimus', 'type': 'Chemical', 'start': 934, 'end': 944, 'mesh': 'D016559'}, {'text': 'cyclosporine', 'type': 'Chemical', 'start': 948, 'end': 960, 'mesh': 'D016572'}, {'text': 'Posterior reversible encephalopathy syndrome', 'type': 'Disease', 'start': 1130, 'end': 1174, 'mesh': 'D054038'}]"
+1475,19728177,Prolonged hypothermia as a bridge to recovery for cerebral edema and intracranial hypertension associated with fulminant hepatic failure.,"BACKGROUND: To review evidence-based treatment options in patients with cerebral edema complicating fulminant hepatic failure (FHF) and discuss the potential applications of hypothermia. METHOD: Case-based observations from a medical intensive care unit (MICU) in a tertiary care facility in a 27-year-old female with FHF from acetaminophen and resultant cerebral edema. RESULTS: Our patient was admitted to the MICU after being found unresponsive with presumed toxicity from acetaminophen which was ingested over a 2-day period. The patient had depressed of mental status lasting at least 24 h prior to admission. Initial evaluation confirmed FHF from acetaminophen and cerebral edema. The patient was treated with hyperosmolar therapy, hyperventilation, sedation, and chemical paralysis. Her intracranial pressure remained elevated despite maximal medical therapy. We then initiated therapeutic hypothermia which was continued for 5 days. At re-warming, patient had resolution of her cerebral edema and intracranial hypertension. At discharge, she had complete recovery of neurological and hepatic functions. CONCLUSION: In patients with FHF and cerebral edema from acetaminophen overdose, prolonged therapeutic hypothermia could potentially be used as a life saving therapy and a bridge to hepatic and neurological recovery. A clinical trial of hypothermia in patients with this condition is warranted.","[{'text': 'hypothermia', 'type': 'Disease', 'start': 10, 'end': 21, 'mesh': 'D007035'}, {'text': 'cerebral edema', 'type': 'Disease', 'start': 50, 'end': 64, 'mesh': 'D001929'}, {'text': 'intracranial hypertension', 'type': 'Disease', 'start': 69, 'end': 94, 'mesh': 'D019586'}, {'text': 'fulminant hepatic failure', 'type': 'Disease', 'start': 111, 'end': 136, 'mesh': 'D017114'}, {'text': 'cerebral edema', 'type': 'Disease', 'start': 210, 'end': 224, 'mesh': 'D001929'}, {'text': 'fulminant hepatic failure', 'type': 'Disease', 'start': 238, 'end': 263, 'mesh': 'D017114'}, {'text': 'FHF', 'type': 'Disease', 'start': 265, 'end': 268, 'mesh': 'D017114'}, {'text': 'hypothermia', 'type': 'Disease', 'start': 312, 'end': 323, 'mesh': 'D007035'}, {'text': 'FHF', 'type': 'Disease', 'start': 456, 'end': 459, 'mesh': 'D017114'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 465, 'end': 478, 'mesh': 'D000082'}, {'text': 'cerebral edema', 'type': 'Disease', 'start': 493, 'end': 507, 'mesh': 'D001929'}, {'text': 'toxicity', 'type': 'Disease', 'start': 600, 'end': 608, 'mesh': 'D064420'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 614, 'end': 627, 'mesh': 'D000082'}, {'text': 'FHF', 'type': 'Disease', 'start': 782, 'end': 785, 'mesh': 'D017114'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 791, 'end': 804, 'mesh': 'D000082'}, {'text': 'cerebral edema', 'type': 'Disease', 'start': 809, 'end': 823, 'mesh': 'D001929'}, {'text': 'hyperventilation', 'type': 'Disease', 'start': 876, 'end': 892, 'mesh': 'D006985'}, {'text': 'paralysis', 'type': 'Disease', 'start': 917, 'end': 926, 'mesh': 'D010243'}, {'text': 'hypothermia', 'type': 'Disease', 'start': 1035, 'end': 1046, 'mesh': 'D007035'}, {'text': 'cerebral edema', 'type': 'Disease', 'start': 1124, 'end': 1138, 'mesh': 'D001929'}, {'text': 'intracranial hypertension', 'type': 'Disease', 'start': 1143, 'end': 1168, 'mesh': 'D019586'}, {'text': 'FHF', 'type': 'Disease', 'start': 1278, 'end': 1281, 'mesh': 'D017114'}, {'text': 'cerebral edema', 'type': 'Disease', 'start': 1286, 'end': 1300, 'mesh': 'D001929'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 1306, 'end': 1319, 'mesh': 'D000082'}, {'text': 'overdose', 'type': 'Disease', 'start': 1320, 'end': 1328, 'mesh': 'D062787'}, {'text': 'hypothermia', 'type': 'Disease', 'start': 1352, 'end': 1363, 'mesh': 'D007035'}, {'text': 'hypothermia', 'type': 'Disease', 'start': 1486, 'end': 1497, 'mesh': 'D007035'}]"
+1476,19815465,Binasal visual field defects are not specific to vigabatrin.,"This study investigated the visual defects associated with the antiepileptic drug vigabatrin (VGB). Two hundred four people with epilepsy were grouped on the basis of antiepileptic drug therapy (current, previous, or no exposure to VGB). Groups were matched with respect to age, gender, and seizure frequency. All patients underwent objective assessment of electrophysiological function (wide-field multifocal electroretinography) and conventional visual field testing (static perimetry). Bilateral visual field constriction was observed in 59% of patients currently taking VGB, 43% of patients who previously took VGB, and 24% of patients with no exposure to VGB. Assessment of retinal function revealed abnormal responses in 48% of current VGB users and 22% of prior VGB users, but in none of the patients without previous exposure to VGB. Bilateral visual field abnormalities are common in the treated epilepsy population, irrespective of drug history. Assessment by conventional static perimetry may neither be sufficiently sensitive nor specific to reliably identify retinal toxicity associated with VGB.","[{'text': 'Binasal visual field defects', 'type': 'Disease', 'start': 0, 'end': 28, 'mesh': 'D014786'}, {'text': 'vigabatrin', 'type': 'Chemical', 'start': 49, 'end': 59, 'mesh': 'D020888'}, {'text': 'visual defects', 'type': 'Disease', 'start': 89, 'end': 103, 'mesh': 'D014786'}, {'text': 'vigabatrin', 'type': 'Chemical', 'start': 143, 'end': 153, 'mesh': 'D020888'}, {'text': 'VGB', 'type': 'Chemical', 'start': 155, 'end': 158, 'mesh': 'D020888'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 190, 'end': 198, 'mesh': 'D004827'}, {'text': 'VGB', 'type': 'Chemical', 'start': 293, 'end': 296, 'mesh': 'D020888'}, {'text': 'seizure', 'type': 'Disease', 'start': 352, 'end': 359, 'mesh': 'D012640'}, {'text': 'VGB', 'type': 'Chemical', 'start': 635, 'end': 638, 'mesh': 'D020888'}, {'text': 'VGB', 'type': 'Chemical', 'start': 676, 'end': 679, 'mesh': 'D020888'}, {'text': 'VGB', 'type': 'Chemical', 'start': 721, 'end': 724, 'mesh': 'D020888'}, {'text': 'VGB', 'type': 'Chemical', 'start': 803, 'end': 806, 'mesh': 'D020888'}, {'text': 'VGB', 'type': 'Chemical', 'start': 830, 'end': 833, 'mesh': 'D020888'}, {'text': 'VGB', 'type': 'Chemical', 'start': 898, 'end': 901, 'mesh': 'D020888'}, {'text': 'Bilateral visual field abnormalities', 'type': 'Disease', 'start': 903, 'end': 939, 'mesh': 'D014786'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 966, 'end': 974, 'mesh': 'D004827'}, {'text': 'retinal toxicity', 'type': 'Disease', 'start': 1133, 'end': 1149, 'mesh': 'D012164'}, {'text': 'VGB', 'type': 'Chemical', 'start': 1166, 'end': 1169, 'mesh': 'D020888'}]"
+1477,19841052,Smoking of crack cocaine as a risk factor for HIV infection among people who use injection drugs.,"BACKGROUND: Little is known about the possible role that smoking crack cocaine has on the incidence of HIV infection. Given the increasing use of crack cocaine, we sought to examine whether use of this illicit drug has become a risk factor for HIV infection. METHODS: We included data from people participating in the Vancouver Injection Drug Users Study who reported injecting illicit drugs at least once in the month before enrolment, lived in the greater Vancouver area, were HIV-negative at enrolment and completed at least 1 follow-up study visit. To determine whether the risk of HIV seroconversion among daily smokers of crack cocaine changed over time, we used Cox proportional hazards regression and divided the study into 3 periods: May 1, 1996-Nov. 30, 1999 (period 1), Dec. 1, 1999-Nov. 30, 2002 (period 2), and Dec. 1, 2002-Dec. 30, 2005 (period 3). RESULTS: Overall, 1048 eligible injection drug users were included in our study. Of these, 137 acquired HIV infection during follow-up. The mean proportion of participants who reported daily smoking of crack cocaine increased from 11.6% in period 1 to 39.7% in period 3. After adjusting for potential confounders, we found that the risk of HIV seroconversion among participants who were daily smokers of crack cocaine increased over time (period 1: hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.57-1.85; period 2: HR 1.68, 95% CI 1.01-2.80; and period 3: HR 2.74, 95% CI 1.06-7.11). INTERPRETATION: Smoking of crack cocaine was found to be an independent risk factor for HIV seroconversion among people who were injection drug users. This finding points to the urgent need for evidence-based public health initiatives targeted at people who smoke crack cocaine.","[{'text': 'crack cocaine', 'type': 'Chemical', 'start': 11, 'end': 24, 'mesh': 'D016578'}, {'text': 'HIV infection', 'type': 'Disease', 'start': 46, 'end': 59, 'mesh': 'D015658'}, {'text': 'crack cocaine', 'type': 'Chemical', 'start': 163, 'end': 176, 'mesh': 'D016578'}, {'text': 'HIV infection', 'type': 'Disease', 'start': 201, 'end': 214, 'mesh': 'D015658'}, {'text': 'crack cocaine', 'type': 'Chemical', 'start': 244, 'end': 257, 'mesh': 'D016578'}, {'text': 'HIV infection', 'type': 'Disease', 'start': 342, 'end': 355, 'mesh': 'D015658'}, {'text': 'HIV seroconversion', 'type': 'Disease', 'start': 684, 'end': 702, 'mesh': 'D006679'}, {'text': 'crack cocaine', 'type': 'Chemical', 'start': 726, 'end': 739, 'mesh': 'D016578'}, {'text': 'HIV infection', 'type': 'Disease', 'start': 1065, 'end': 1078, 'mesh': 'D015658'}, {'text': 'crack cocaine', 'type': 'Chemical', 'start': 1163, 'end': 1176, 'mesh': 'D016578'}, {'text': 'HIV seroconversion', 'type': 'Disease', 'start': 1301, 'end': 1319, 'mesh': 'D006679'}, {'text': 'crack cocaine', 'type': 'Chemical', 'start': 1365, 'end': 1378, 'mesh': 'D016578'}, {'text': 'crack cocaine', 'type': 'Chemical', 'start': 1580, 'end': 1593, 'mesh': 'D016578'}, {'text': 'HIV seroconversion', 'type': 'Disease', 'start': 1641, 'end': 1659, 'mesh': 'D006679'}, {'text': 'crack cocaine', 'type': 'Chemical', 'start': 1817, 'end': 1830, 'mesh': 'D016578'}]"
+1478,19914299,Fluoxetine improves the memory deficits caused by the chemotherapy agent 5-fluorouracil.,"Cancer patients who have been treated with systemic adjuvant chemotherapy have described experiencing deteriorations in cognition. A widely used chemotherapeutic agent, 5-fluorouracil (5-FU), readily crosses the blood-brain barrier and so could have a direct effect on brain function. In particular this anti mitotic drug could reduce cell proliferation in the neurogenic regions of the adult brain. In contrast reports indicate that hippocampal dependent neurogenesis and cognition are enhanced by the SSRI antidepressant Fluoxetine. In this investigation the behavioural effects of chronic (two week) treatment with 5-FU and (three weeks) with Fluoxetine either separately or in combination with 5-FU were tested on adult Lister hooded rats. Behavioural effects were tested using a context dependent conditioned emotional response test (CER) which showed that animals treated with 5-FU had a significant reduction in freezing time compared to controls. A separate group of animals was tested using a hippocampal dependent spatial working memory test, the object location recognition test (OLR). Animals treated only with 5-FU showed significant deficits in their ability to carry out the OLR task but co administration of Fluoxetine improved their performance. 5-FU chemotherapy caused a significant reduction in the number of proliferating cells in the sub granular zone of the dentate gyrus compared to controls. This reduction was eliminated when Fluoxetine was co administered with 5-FU. Fluoxetine on its own had no effect on proliferating cell number or behaviour. These findings suggest that 5-FU can negatively affect both cell proliferation and hippocampal dependent working memory and that these deficits can be reversed by the simultaneous administration of the antidepressant Fluoxetine.","[{'text': 'Fluoxetine', 'type': 'Chemical', 'start': 0, 'end': 10, 'mesh': 'D005473'}, {'text': 'memory deficits', 'type': 'Disease', 'start': 24, 'end': 39, 'mesh': 'D008569'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 73, 'end': 87, 'mesh': 'D005472'}, {'text': 'Cancer', 'type': 'Disease', 'start': 89, 'end': 95, 'mesh': 'D009369'}, {'text': '5-fluorouracil', 'type': 'Chemical', 'start': 258, 'end': 272, 'mesh': 'D005472'}, {'text': '5-FU', 'type': 'Chemical', 'start': 274, 'end': 278, 'mesh': 'D005472'}, {'text': 'SSRI', 'type': 'Chemical', 'start': 592, 'end': 596, 'mesh': 'D017367'}, {'text': 'Fluoxetine', 'type': 'Chemical', 'start': 612, 'end': 622, 'mesh': 'D005473'}, {'text': '5-FU', 'type': 'Chemical', 'start': 707, 'end': 711, 'mesh': 'D005472'}, {'text': 'Fluoxetine', 'type': 'Chemical', 'start': 735, 'end': 745, 'mesh': 'D005473'}, {'text': '5-FU', 'type': 'Chemical', 'start': 787, 'end': 791, 'mesh': 'D005472'}, {'text': '5-FU', 'type': 'Chemical', 'start': 972, 'end': 976, 'mesh': 'D005472'}, {'text': '5-FU', 'type': 'Chemical', 'start': 1212, 'end': 1216, 'mesh': 'D005472'}, {'text': 'Fluoxetine', 'type': 'Chemical', 'start': 1313, 'end': 1323, 'mesh': 'D005473'}, {'text': '5-FU', 'type': 'Chemical', 'start': 1352, 'end': 1356, 'mesh': 'D005472'}, {'text': 'Fluoxetine', 'type': 'Chemical', 'start': 1541, 'end': 1551, 'mesh': 'D005473'}, {'text': '5-FU', 'type': 'Chemical', 'start': 1577, 'end': 1581, 'mesh': 'D005472'}, {'text': 'Fluoxetine', 'type': 'Chemical', 'start': 1583, 'end': 1593, 'mesh': 'D005473'}, {'text': '5-FU', 'type': 'Chemical', 'start': 1690, 'end': 1694, 'mesh': 'D005472'}, {'text': 'Fluoxetine', 'type': 'Chemical', 'start': 1879, 'end': 1889, 'mesh': 'D005473'}]"
+1479,19920070,Liver-specific ablation of integrin-linked kinase in mice results in enhanced and prolonged cell proliferation and hepatomegaly after phenobarbital administration.,"We have recently demonstrated that disruption of extracellular matrix (ECM)/integrin signaling via elimination of integrin-linked kinase (ILK) in hepatocytes interferes with signals leading to termination of liver regeneration. This study investigates the role of ILK in liver enlargement induced by phenobarbital (PB). Wild-type (WT) and ILK:liver-/- mice were given PB (0.1% in drinking water) for 10 days. Livers were harvested on 2, 5, and 10 days during PB administration. In the hepatocyte-specific ILK/liver-/- mice, the liver:body weight ratio was more than double as compared to 0 h at day 2 (2.5 times), while at days 5 and 10, it was enlarged three times. In the WT mice, the increase was as expected from previous literature (1.8 times) and seems to have leveled off after day 2. There were slightly increased proliferating cell nuclear antigen-positive cells in the ILK/liver-/- animals at day 2 as compared to WT after PB administration. In the WT animals, the proliferative response had come back to normal by days 5 and 10. Hepatocytes of the ILK/liver-/- mice continued to proliferate up until day 10. ILK/liver-/- mice also showed increased expression of key genes involved in hepatocyte proliferation at different time points during PB administration. In summary, ECM proteins communicate with the signaling machinery of dividing cells via ILK to regulate hepatocyte proliferation and termination of the proliferative response. Lack of ILK in the hepatocytes imparts prolonged proliferative response not only to stimuli related to liver regeneration but also to xenobiotic chemical mitogens, such as PB.","[{'text': 'hepatomegaly', 'type': 'Disease', 'start': 115, 'end': 127, 'mesh': 'D006529'}, {'text': 'phenobarbital', 'type': 'Chemical', 'start': 134, 'end': 147, 'mesh': 'D010634'}, {'text': 'phenobarbital', 'type': 'Chemical', 'start': 464, 'end': 477, 'mesh': 'D010634'}, {'text': 'PB', 'type': 'Chemical', 'start': 479, 'end': 481, 'mesh': 'D010634'}, {'text': 'PB', 'type': 'Chemical', 'start': 532, 'end': 534, 'mesh': 'D010634'}, {'text': 'PB', 'type': 'Chemical', 'start': 623, 'end': 625, 'mesh': 'D010634'}, {'text': 'PB', 'type': 'Chemical', 'start': 1097, 'end': 1099, 'mesh': 'D010634'}, {'text': 'PB', 'type': 'Chemical', 'start': 1416, 'end': 1418, 'mesh': 'D010634'}, {'text': 'PB', 'type': 'Chemical', 'start': 1783, 'end': 1785, 'mesh': 'D010634'}]"
+1480,19967075,"Decreased Expression of Na/K-ATPase, NHE3, NBC1, AQP1 and OAT in Gentamicin-induced Nephropathy.","The present study was aimed to determine whether there is an altered regulation of tubular transporters in gentamicin-induced nephropathy. Sprague-Dawley male rats (200~250 g) were subcutaneously injected with gentamicin (100 mg/kg per day) for 7 days, and the expression of tubular transporters was determined by immunoblotting and immunohistochemistry. The mRNA and protein expression of OAT was also determined. Gentamicin-treated rats exhibited significantly decreased creatinine clearance along with increased plasma creatinine levels. Accordingly, the fractional excretion of sodium increased. Urine volume was increased, while urine osmolality and free water reabsorption were decreased. Immunoblotting and immunohistochemistry revealed decreased expression of Na(+)/K(+)-ATPase, NHE3, NBC1, and AQP1 in the kidney of gentamicin-treated rats. The expression of OAT1 and OAT3 was also decreased. Gentamicin-induced nephropathy may at least in part be causally related with a decreased expression of Na(+)/K(+)-ATPase, NHE3, NBC1, AQP1 and OAT.","[{'text': 'Na', 'type': 'Chemical', 'start': 24, 'end': 26, 'mesh': 'D012964'}, {'text': 'K', 'type': 'Chemical', 'start': 27, 'end': 28, 'mesh': 'D011188'}, {'text': 'Gentamicin', 'type': 'Chemical', 'start': 65, 'end': 75, 'mesh': 'D005839'}, {'text': 'Nephropathy', 'type': 'Disease', 'start': 84, 'end': 95, 'mesh': 'D007674'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 204, 'end': 214, 'mesh': 'D005839'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 223, 'end': 234, 'mesh': 'D007674'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 307, 'end': 317, 'mesh': 'D005839'}, {'text': 'Gentamicin', 'type': 'Chemical', 'start': 512, 'end': 522, 'mesh': 'D005839'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 570, 'end': 580, 'mesh': 'D003404'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 619, 'end': 629, 'mesh': 'D003404'}, {'text': 'sodium', 'type': 'Chemical', 'start': 679, 'end': 685, 'mesh': 'D012964'}, {'text': 'Na', 'type': 'Chemical', 'start': 865, 'end': 867, 'mesh': 'D012964'}, {'text': 'K', 'type': 'Chemical', 'start': 871, 'end': 872, 'mesh': 'D011188'}, {'text': 'gentamicin', 'type': 'Chemical', 'start': 922, 'end': 932, 'mesh': 'D005839'}, {'text': 'Gentamicin', 'type': 'Chemical', 'start': 999, 'end': 1009, 'mesh': 'D005839'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1018, 'end': 1029, 'mesh': 'D007674'}, {'text': 'Na', 'type': 'Chemical', 'start': 1102, 'end': 1104, 'mesh': 'D012964'}, {'text': 'K', 'type': 'Chemical', 'start': 1108, 'end': 1109, 'mesh': 'D011188'}]"
+1481,20024739,Longitudinal association of alcohol use with HIV disease progression and psychological health of women with HIV.,"We evaluated the association of alcohol consumption and depression, and their effects on HIV disease progression among women with HIV. The study included 871 women with HIV who were recruited from 1993-1995 in four US cities. The participants had physical examination, medical record extraction, and venipuncture, CD4+T-cell counts determination, measurement of depression symptoms (using the self-report Center for Epidemiological Studies-Depression Scale), and alcohol use assessment at enrollment, and semiannually until March 2000. Multilevel random coefficient ordinal models as well as multilevel models with joint responses were used in the analysis. There was no significant association between level of alcohol use and CD4+ T-cell counts. When participants were stratified by antiretroviral therapy (ART) use, the association between alcohol and CD4+ T-cell did not reach statistical significance. The association between alcohol consumption and depression was significant (p<0.001). Depression had a significant negative effect on CD4+ T-cell counts over time regardless of ART use. Our findings suggest that alcohol consumption has a direct association with depression. Moreover, depression is associated with HIV disease progression. Our findings have implications for the provision of alcohol use interventions and psychological resources to improve the health of women with HIV.","[{'text': 'alcohol', 'type': 'Chemical', 'start': 28, 'end': 35, 'mesh': 'D000431'}, {'text': 'HIV disease', 'type': 'Disease', 'start': 45, 'end': 56, 'mesh': 'D015658'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 145, 'end': 152, 'mesh': 'D000431'}, {'text': 'depression', 'type': 'Disease', 'start': 169, 'end': 179, 'mesh': 'D003866'}, {'text': 'HIV disease', 'type': 'Disease', 'start': 202, 'end': 213, 'mesh': 'D015658'}, {'text': 'depression', 'type': 'Disease', 'start': 475, 'end': 485, 'mesh': 'D003866'}, {'text': 'Depression', 'type': 'Disease', 'start': 553, 'end': 563, 'mesh': 'D003866'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 576, 'end': 583, 'mesh': 'D000431'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 825, 'end': 832, 'mesh': 'D000431'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 956, 'end': 963, 'mesh': 'D000431'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 1044, 'end': 1051, 'mesh': 'D000431'}, {'text': 'depression', 'type': 'Disease', 'start': 1068, 'end': 1078, 'mesh': 'D003866'}, {'text': 'Depression', 'type': 'Disease', 'start': 1106, 'end': 1116, 'mesh': 'D003866'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 1232, 'end': 1239, 'mesh': 'D000431'}, {'text': 'depression', 'type': 'Disease', 'start': 1282, 'end': 1292, 'mesh': 'D003866'}, {'text': 'depression', 'type': 'Disease', 'start': 1304, 'end': 1314, 'mesh': 'D003866'}, {'text': 'HIV disease', 'type': 'Disease', 'start': 1334, 'end': 1345, 'mesh': 'D015658'}, {'text': 'alcohol', 'type': 'Chemical', 'start': 1411, 'end': 1418, 'mesh': 'D000431'}]"
+1482,20034406,Chemokine CCL2 and its receptor CCR2 are increased in the hippocampus following pilocarpine-induced status epilepticus.,"BACKGROUND: Neuroinflammation occurs after seizures and is implicated in epileptogenesis. CCR2 is a chemokine receptor for CCL2 and their interaction mediates monocyte infiltration in the neuroinflammatory cascade triggered in different brain pathologies. In this work CCR2 and CCL2 expression were examined following status epilepticus (SE) induced by pilocarpine injection. METHODS: SE was induced by pilocarpine injection. Control rats were injected with saline instead of pilocarpine. Five days after SE, CCR2 staining in neurons and glial cells was examined using imunohistochemical analyses. The number of CCR2 positive cells was determined using stereology probes in the hippocampus. CCL2 expression in the hippocampus was examined by molecular assay. RESULTS: Increased CCR2 was observed in the hippocampus after SE. Seizures also resulted in alterations to the cell types expressing CCR2. Increased numbers of neurons that expressed CCR2 was observed following SE. Microglial cells were more closely apposed to the CCR2-labeled cells in SE rats. In addition, rats that experienced SE exhibited CCR2-labeling in populations of hypertrophied astrocytes, especially in CA1 and dentate gyrus. These CCR2+ astroctytes were not observed in control rats. Examination of CCL2 expression showed that it was elevated in the hippocampus following SE. CONCLUSION: The data show that CCR2 and CCL2 are up-regulated in the hippocampus after pilocarpine-induced SE. Seizures also result in changes to CCR2 receptor expression in neurons and astrocytes. These changes might be involved in detrimental neuroplasticity and neuroinflammatory changes that occur following seizures.","[{'text': 'pilocarpine', 'type': 'Chemical', 'start': 80, 'end': 91, 'mesh': 'D010862'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 100, 'end': 118, 'mesh': 'D013226'}, {'text': 'Neuroinflammation', 'type': 'Disease', 'start': 132, 'end': 149, 'mesh': 'D007249'}, {'text': 'seizures', 'type': 'Disease', 'start': 163, 'end': 171, 'mesh': 'D012640'}, {'text': 'neuroinflammatory', 'type': 'Disease', 'start': 308, 'end': 325, 'mesh': 'D007249'}, {'text': 'status epilepticus', 'type': 'Disease', 'start': 438, 'end': 456, 'mesh': 'D013226'}, {'text': 'SE', 'type': 'Disease', 'start': 458, 'end': 460, 'mesh': 'D013226'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 473, 'end': 484, 'mesh': 'D010862'}, {'text': 'SE', 'type': 'Disease', 'start': 505, 'end': 507, 'mesh': 'D013226'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 523, 'end': 534, 'mesh': 'D010862'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 596, 'end': 607, 'mesh': 'D010862'}, {'text': 'SE', 'type': 'Disease', 'start': 625, 'end': 627, 'mesh': 'D013226'}, {'text': 'SE', 'type': 'Disease', 'start': 941, 'end': 943, 'mesh': 'D013226'}, {'text': 'Seizures', 'type': 'Disease', 'start': 945, 'end': 953, 'mesh': 'D012640'}, {'text': 'SE', 'type': 'Disease', 'start': 1090, 'end': 1092, 'mesh': 'D013226'}, {'text': 'SE', 'type': 'Disease', 'start': 1166, 'end': 1168, 'mesh': 'D013226'}, {'text': 'SE', 'type': 'Disease', 'start': 1210, 'end': 1212, 'mesh': 'D013226'}, {'text': 'hypertrophied', 'type': 'Disease', 'start': 1255, 'end': 1268, 'mesh': 'D006984'}, {'text': 'SE', 'type': 'Disease', 'start': 1465, 'end': 1467, 'mesh': 'D013226'}, {'text': 'pilocarpine', 'type': 'Chemical', 'start': 1556, 'end': 1567, 'mesh': 'D010862'}, {'text': 'SE', 'type': 'Disease', 'start': 1576, 'end': 1578, 'mesh': 'D013226'}, {'text': 'Seizures', 'type': 'Disease', 'start': 1580, 'end': 1588, 'mesh': 'D012640'}, {'text': 'neuroinflammatory', 'type': 'Disease', 'start': 1734, 'end': 1751, 'mesh': 'D007249'}, {'text': 'seizures', 'type': 'Disease', 'start': 1781, 'end': 1789, 'mesh': 'D012640'}]"
+1483,20046642,Metallothionein induction reduces caspase-3 activity and TNFalpha levels with preservation of cognitive function and intact hippocampal neurons in carmustine-treated rats.,"Hippocampal integrity is essential for cognitive functions. On the other hand, induction of metallothionein (MT) by ZnSO(4) and its role in neuroprotection has been documented. The present study aimed to explore the effect of MT induction on carmustine (BCNU)-induced hippocampal cognitive dysfunction in rats. A total of 60 male Wistar albino rats were randomly divided into four groups (15/group): The control group injected with single doses of normal saline (i.c.v) followed 24 h later by BCNU solvent (i.v). The second group administered ZnSO(4) (0.1 micromol/10 microl normal saline, i.c.v, once) then BCNU solvent (i.v) after 24 h. Third group received BCNU (20 mg/kg, i.v, once) 24 h after injection with normal saline (i.c.v). Fourth group received a single dose of ZnSO(4) (0.1 micromol/10 microl normal saline, i.c.v) then BCNU (20 mg/kg, i.v, once) after 24 h. The obtained data revealed that BCNU administration resulted in deterioration of learning and short-term memory (STM), as measured by using radial arm water maze, accompanied with decreased hippocampal glutathione reductase (GR) activity and reduced glutathione (GSH) content. Also, BCNU administration increased serum tumor necrosis factor-alpha (TNFalpha), hippocampal MT and malondialdehyde (MDA) contents as well as caspase-3 activity in addition to histological alterations. ZnSO(4) pretreatment counteracted BCNU-induced inhibition of GR and depletion of GSH and resulted in significant reduction in the levels of MDA and TNFalpha as well as the activity of caspase-3. The histological features were improved in hippocampus of rats treated with ZnSO(4) + BCNU compared to only BCNU-treated animals. In conclusion, MT induction halts BCNU-induced hippocampal toxicity as it prevented GR inhibition and GSH depletion and counteracted the increased levels of TNFalpha, MDA and caspase-3 activity with subsequent preservation of cognition.","[{'text': 'Metallothionein', 'type': 'Chemical', 'start': 0, 'end': 15, 'mesh': 'D008668'}, {'text': 'carmustine', 'type': 'Chemical', 'start': 147, 'end': 157, 'mesh': 'D002330'}, {'text': 'metallothionein', 'type': 'Chemical', 'start': 264, 'end': 279, 'mesh': 'D008668'}, {'text': 'MT', 'type': 'Chemical', 'start': 281, 'end': 283, 'mesh': 'D008668'}, {'text': 'ZnSO(4)', 'type': 'Chemical', 'start': 288, 'end': 295, 'mesh': 'D019287'}, {'text': 'MT', 'type': 'Chemical', 'start': 398, 'end': 400, 'mesh': 'D008668'}, {'text': 'carmustine', 'type': 'Chemical', 'start': 414, 'end': 424, 'mesh': 'D002330'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 426, 'end': 430, 'mesh': 'D002330'}, {'text': 'cognitive dysfunction', 'type': 'Disease', 'start': 452, 'end': 473, 'mesh': 'D003072'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 665, 'end': 669, 'mesh': 'D002330'}, {'text': 'ZnSO(4)', 'type': 'Chemical', 'start': 715, 'end': 722, 'mesh': 'D019287'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 780, 'end': 784, 'mesh': 'D002330'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 832, 'end': 836, 'mesh': 'D002330'}, {'text': 'ZnSO(4)', 'type': 'Chemical', 'start': 947, 'end': 954, 'mesh': 'D019287'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 1006, 'end': 1010, 'mesh': 'D002330'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 1077, 'end': 1081, 'mesh': 'D002330'}, {'text': 'glutathione', 'type': 'Chemical', 'start': 1247, 'end': 1258, 'mesh': 'D005978'}, {'text': 'glutathione', 'type': 'Chemical', 'start': 1295, 'end': 1306, 'mesh': 'D005978'}, {'text': 'GSH', 'type': 'Chemical', 'start': 1308, 'end': 1311, 'mesh': 'D005978'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 1328, 'end': 1332, 'mesh': 'D002330'}, {'text': 'tumor', 'type': 'Disease', 'start': 1364, 'end': 1369, 'mesh': 'D009369'}, {'text': 'necrosis', 'type': 'Disease', 'start': 1370, 'end': 1378, 'mesh': 'D009336'}, {'text': 'MT', 'type': 'Chemical', 'start': 1416, 'end': 1418, 'mesh': 'D008668'}, {'text': 'malondialdehyde', 'type': 'Chemical', 'start': 1423, 'end': 1438, 'mesh': 'D008315'}, {'text': 'MDA', 'type': 'Chemical', 'start': 1440, 'end': 1443, 'mesh': 'D008315'}, {'text': 'ZnSO(4)', 'type': 'Chemical', 'start': 1525, 'end': 1532, 'mesh': 'D019287'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 1559, 'end': 1563, 'mesh': 'D002330'}, {'text': 'GSH', 'type': 'Chemical', 'start': 1606, 'end': 1609, 'mesh': 'D005978'}, {'text': 'MDA', 'type': 'Chemical', 'start': 1665, 'end': 1668, 'mesh': 'D008315'}, {'text': 'ZnSO(4)', 'type': 'Chemical', 'start': 1796, 'end': 1803, 'mesh': 'D019287'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 1806, 'end': 1810, 'mesh': 'D002330'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 1828, 'end': 1832, 'mesh': 'D002330'}, {'text': 'MT', 'type': 'Chemical', 'start': 1865, 'end': 1867, 'mesh': 'D008668'}, {'text': 'BCNU', 'type': 'Chemical', 'start': 1884, 'end': 1888, 'mesh': 'D002330'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1909, 'end': 1917, 'mesh': 'D064420'}, {'text': 'GSH', 'type': 'Chemical', 'start': 1952, 'end': 1955, 'mesh': 'D005978'}, {'text': 'MDA', 'type': 'Chemical', 'start': 2017, 'end': 2020, 'mesh': 'D008315'}]"
+1484,20129423,"Fatal carbamazepine induced fulminant eosinophilic (hypersensitivity) myocarditis: emphasis on anatomical and histological characteristics, mechanisms and genetics of drug hypersensitivity and differential diagnosis.","The most severe adverse reactions to carbamazepine have been observed in the haemopoietic system, the liver and the cardiovascular system. A frequently fatal, although exceptionally rare side effect of carbamazepine is necrotizing eosinophilic (hypersensitivity) myocarditis. We report a case of hypersensitivity myocarditis secondary to administration of carbamazepine. Acute hypersensitivity myocarditis was not suspected clinically, and the diagnosis was made post-mortem. Histology revealed diffuse infiltration of the myocardium by eosinophils and lymphocytes with myocyte damage. Clinically, death was due to cardiogenic shock. To best of our knowledge this is the second case of fatal carbamazepine induced myocarditis reported in English literature.","[{'text': 'carbamazepine', 'type': 'Chemical', 'start': 6, 'end': 19, 'mesh': 'D002220'}, {'text': 'fulminant eosinophilic', 'type': 'Disease', 'start': 28, 'end': 50, 'mesh': 'D004802'}, {'text': 'hypersensitivity', 'type': 'Disease', 'start': 52, 'end': 68, 'mesh': 'D004342'}, {'text': 'myocarditis', 'type': 'Disease', 'start': 70, 'end': 81, 'mesh': 'D009205'}, {'text': 'drug hypersensitivity', 'type': 'Disease', 'start': 167, 'end': 188, 'mesh': 'D004342'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 254, 'end': 267, 'mesh': 'D002220'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 419, 'end': 432, 'mesh': 'D002220'}, {'text': 'hypersensitivity', 'type': 'Disease', 'start': 462, 'end': 478, 'mesh': 'D004342'}, {'text': 'myocarditis', 'type': 'Disease', 'start': 480, 'end': 491, 'mesh': 'D009205'}, {'text': 'hypersensitivity', 'type': 'Disease', 'start': 513, 'end': 529, 'mesh': 'D004342'}, {'text': 'myocarditis', 'type': 'Disease', 'start': 530, 'end': 541, 'mesh': 'D009205'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 573, 'end': 586, 'mesh': 'D002220'}, {'text': 'hypersensitivity', 'type': 'Disease', 'start': 594, 'end': 610, 'mesh': 'D004342'}, {'text': 'myocarditis', 'type': 'Disease', 'start': 611, 'end': 622, 'mesh': 'D009205'}, {'text': 'cardiogenic shock', 'type': 'Disease', 'start': 832, 'end': 849, 'mesh': 'D012770'}, {'text': 'carbamazepine', 'type': 'Chemical', 'start': 909, 'end': 922, 'mesh': 'D002220'}, {'text': 'myocarditis', 'type': 'Disease', 'start': 931, 'end': 942, 'mesh': 'D009205'}]"
+1485,20169779,Neuropsychiatric behaviors in the MPTP marmoset model of Parkinson's disease.,"OBJECTIVES: Neuropsychiatric symptoms are increasingly recognised as a significant problem in patients with Parkinson's disease (PD). These symptoms may be due to 'sensitisation' following repeated levodopa treatment or a direct effect of dopamine on the disease state. The levodopa-treated MPTP-lesioned marmoset was used as a model of neuropsychiatric symptoms in PD patients. Here we compare the time course of levodopa-induced motor fluctuations and neuropsychiatric-like behaviors to determine the relationship between duration of treatment and onset of symptoms. METHODS: Marmosets were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (2.0 mg/kg s.c.) for five days, resulting in stable parkinsonism. Levodopa (15 mg/kg and benserazide, 3.75 mg/kg) p.o. b.i.d, was administered for 30 days. Animals were evaluated for parkinsonian disability, dyskinesia and on-time (motor fluctuations) and neuropsychiatric-like behaviors on Day 0 (prior to levodopa) and on Days 1, 7, 13, 27 and 30 of treatment using post hoc DVD analysis by a trained rater, blind to the treatment day. RESULTS: The neuropsychiatric-like behavior rating scale demonstrated high interrater reliability between three trained raters of differing professional backgrounds. As anticipated, animals exhibited a progressive increase in levodopa-induced motor fluctuations, dyskinesia and wearing-off, that correlated with the duration of levodopa therapy. In contrast, levodopa-induced neuropsychiatric-like behaviors were present on Day 1 of levodopa treatment and their severity did not correlate with duration of treatment. CONCLUSIONS: The data suggest that neuropsychiatric disorders in PD are more likely an interaction between levodopa and the disease state than a consequence of sensitisation to repeated dopaminergic therapy.","[{'text': 'MPTP', 'type': 'Chemical', 'start': 34, 'end': 38, 'mesh': 'D015632'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 57, 'end': 76, 'mesh': 'D010302'}, {'text': ""Parkinson's disease"", 'type': 'Disease', 'start': 186, 'end': 205, 'mesh': 'D010302'}, {'text': 'PD', 'type': 'Disease', 'start': 207, 'end': 209, 'mesh': 'D010302'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 276, 'end': 284, 'mesh': 'D007980'}, {'text': 'dopamine', 'type': 'Chemical', 'start': 317, 'end': 325, 'mesh': 'D004298'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 352, 'end': 360, 'mesh': 'D007980'}, {'text': 'MPTP', 'type': 'Chemical', 'start': 369, 'end': 373, 'mesh': 'D015632'}, {'text': 'neuropsychiatric symptoms', 'type': 'Disease', 'start': 415, 'end': 440, 'mesh': 'D001523'}, {'text': 'PD', 'type': 'Disease', 'start': 444, 'end': 446, 'mesh': 'D010302'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 492, 'end': 500, 'mesh': 'D007980'}, {'text': 'neuropsychiatric-like behaviors', 'type': 'Disease', 'start': 532, 'end': 563, 'mesh': 'D001523'}, {'text': '1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine', 'type': 'Chemical', 'start': 684, 'end': 728, 'mesh': 'D015632'}, {'text': 'parkinsonism', 'type': 'Disease', 'start': 781, 'end': 793, 'mesh': 'D010302'}, {'text': 'Levodopa', 'type': 'Chemical', 'start': 795, 'end': 803, 'mesh': 'D007980'}, {'text': 'benserazide', 'type': 'Chemical', 'start': 818, 'end': 829, 'mesh': 'D001545'}, {'text': 'parkinsonian disability', 'type': 'Disease', 'start': 912, 'end': 935, 'mesh': 'D020734'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 937, 'end': 947, 'mesh': 'D004409'}, {'text': 'neuropsychiatric-like behaviors', 'type': 'Disease', 'start': 985, 'end': 1016, 'mesh': 'D001523'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1036, 'end': 1044, 'mesh': 'D007980'}, {'text': 'neuropsychiatric-like behavior', 'type': 'Disease', 'start': 1180, 'end': 1210, 'mesh': 'D001523'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1393, 'end': 1401, 'mesh': 'D007980'}, {'text': 'dyskinesia', 'type': 'Disease', 'start': 1430, 'end': 1440, 'mesh': 'D004409'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1495, 'end': 1503, 'mesh': 'D007980'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1526, 'end': 1534, 'mesh': 'D007980'}, {'text': 'neuropsychiatric-like behaviors', 'type': 'Disease', 'start': 1543, 'end': 1574, 'mesh': 'D001523'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1600, 'end': 1608, 'mesh': 'D007980'}, {'text': 'neuropsychiatric disorders', 'type': 'Disease', 'start': 1719, 'end': 1745, 'mesh': 'D001523'}, {'text': 'PD', 'type': 'Disease', 'start': 1749, 'end': 1751, 'mesh': 'D010302'}, {'text': 'levodopa', 'type': 'Chemical', 'start': 1791, 'end': 1799, 'mesh': 'D007980'}]"
+1486,20192893,Contrast medium nephrotoxicity after renal artery and coronary angioplasty.,"BACKGROUND: Renal dysfunction induced by iodinated contrast medium (CM) administration can minimize the benefit of the interventional procedure in patients undergoing renal angioplasty (PTRA). PURPOSE: To compare the susceptibility to nephrotoxic effect of CM in patients undergoing PTRA with that of patients submitted to percutaneous coronary intervention (PCI). MATERIAL AND METHODS: A total of 33 patients successfully treated with PTRA (PTRA group, mean age 70+/-12 years, 23 female, basal creatinine 1.46+/-0.79, range 0.7-4.9 mg/dl) were compared with 33 patients undergoing successful PCI (PCI group), matched for basal creatinine (1.44+/-0.6, range 0.7-3.4 mg/dl), gender, and age. In both groups postprocedural (48 h) serum creatinine was measured. RESULTS: Postprocedural creatinine level decreased nonsignificantly in the PTRA group (1.46+/-0.8 vs. 1.34+/-0.5 mg/dl, P=NS) and increased significantly in the PCI group (1.44+/-0.6 vs. 1.57+/-0.7 mg/dl, P<0.02). Changes in serum creatinine after intervention (after-before) were significantly different between the PTRA and PCI groups (-0.12+/-0.5 vs. 0.13+/-0.3, P=0.014). This difference was not related to either a different clinical risk profile or to the volume of CM administered. CONCLUSION: In this preliminary study patients submitted to PTRA showed a lower susceptibility to renal damage induced by CM administration than PCI patients. The effectiveness of PTRA on renal function seems to be barely influenced by CM toxicity.","[{'text': 'Contrast medium', 'type': 'Chemical', 'start': 0, 'end': 15, 'mesh': 'D003287'}, {'text': 'nephrotoxicity', 'type': 'Disease', 'start': 16, 'end': 30, 'mesh': 'D007674'}, {'text': 'Renal dysfunction', 'type': 'Disease', 'start': 88, 'end': 105, 'mesh': 'D007674'}, {'text': 'contrast medium', 'type': 'Chemical', 'start': 127, 'end': 142, 'mesh': 'D003287'}, {'text': 'CM', 'type': 'Chemical', 'start': 144, 'end': 146, 'mesh': 'D003287'}, {'text': 'nephrotoxic', 'type': 'Disease', 'start': 311, 'end': 322, 'mesh': 'D007674'}, {'text': 'CM', 'type': 'Chemical', 'start': 333, 'end': 335, 'mesh': 'D003287'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 571, 'end': 581, 'mesh': 'D003404'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 704, 'end': 714, 'mesh': 'D003404'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 810, 'end': 820, 'mesh': 'D003404'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 859, 'end': 869, 'mesh': 'D003404'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 1066, 'end': 1076, 'mesh': 'D003404'}, {'text': 'CM', 'type': 'Chemical', 'start': 1307, 'end': 1309, 'mesh': 'D003287'}, {'text': 'renal damage', 'type': 'Disease', 'start': 1422, 'end': 1434, 'mesh': 'D007674'}, {'text': 'CM', 'type': 'Chemical', 'start': 1446, 'end': 1448, 'mesh': 'D003287'}, {'text': 'CM', 'type': 'Chemical', 'start': 1560, 'end': 1562, 'mesh': 'D003287'}, {'text': 'toxicity', 'type': 'Disease', 'start': 1563, 'end': 1571, 'mesh': 'D064420'}]"
+1487,20408947,Medical and psychiatric outcomes for patients transplanted for acetaminophen-induced acute liver failure: a case-control study.,"BACKGROUND: Acetaminophen-induced hepatotoxicity is the most common cause of acute liver failure (ALF) in the UK. Patients often consume the drug with suicidal intent or with a background of substance dependence. AIMS AND METHODS: We compared the severity of pretransplant illness, psychiatric co-morbidity, medical and psychosocial outcomes of all patients who had undergone liver transplantation (LT) emergently between 1999-2004 for acetaminophen-induced ALF (n=36) with age- and sex-matched patients undergoing emergent LT for non-acetaminophen-induced ALF (n=35) and elective LT for chronic liver disease (CLD, n=34). RESULTS: Acetaminophen-induced ALF patients undergoing LT had a greater severity of pre-LT illness reflected by higher Acute Physiology and Chronic Health Evaluation II scores and requirement for organ support compared with the other two groups. Twenty (56%) acetaminophen-induced ALF patients had a formal psychiatric diagnosis before LT (non-acetaminophen-induced ALF=0/35, CLD=2/34; P<0.01 for all) and nine (25%) had a previous suicide attempt. During follow-up (median 5 years), there were no significant differences in rejection (acute and chronic), graft failure or survival between the groups (acetaminophen-induced ALF 1 year 87%, 5 years 75%; non-acetaminophen-induced ALF 88%, 78%; CLD 93%, 82%: P>0.6 log rank). Two acetaminophen-induced ALF patients reattempted suicide post-LT (one died 8 years post-LT). CONCLUSIONS: Despite a high prevalence of psychiatric disturbance, outcomes for patients transplanted emergently for acetaminophen-induced ALF were comparable to those transplanted for non-acetaminophen-induced ALF and electively for CLD. Multidisciplinary approaches with long-term psychiatric follow-up may contribute to low post-transplant suicide rates seen and low rates of graft loss because of non-compliance.","[{'text': 'acetaminophen', 'type': 'Chemical', 'start': 63, 'end': 76, 'mesh': 'D000082'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 85, 'end': 104, 'mesh': 'D017114'}, {'text': 'Acetaminophen', 'type': 'Chemical', 'start': 140, 'end': 153, 'mesh': 'D000082'}, {'text': 'hepatotoxicity', 'type': 'Disease', 'start': 162, 'end': 176, 'mesh': 'D056486'}, {'text': 'acute liver failure', 'type': 'Disease', 'start': 205, 'end': 224, 'mesh': 'D017114'}, {'text': 'ALF', 'type': 'Disease', 'start': 226, 'end': 229, 'mesh': 'D017114'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 564, 'end': 577, 'mesh': 'D000082'}, {'text': 'ALF', 'type': 'Disease', 'start': 586, 'end': 589, 'mesh': 'D017114'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 663, 'end': 676, 'mesh': 'D000082'}, {'text': 'ALF', 'type': 'Disease', 'start': 685, 'end': 688, 'mesh': 'D017114'}, {'text': 'chronic liver disease', 'type': 'Disease', 'start': 716, 'end': 737, 'mesh': 'D008107'}, {'text': 'CLD', 'type': 'Disease', 'start': 739, 'end': 742, 'mesh': 'D008107'}, {'text': 'Acetaminophen', 'type': 'Chemical', 'start': 760, 'end': 773, 'mesh': 'D000082'}, {'text': 'ALF', 'type': 'Disease', 'start': 782, 'end': 785, 'mesh': 'D017114'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 1010, 'end': 1023, 'mesh': 'D000082'}, {'text': 'ALF', 'type': 'Disease', 'start': 1032, 'end': 1035, 'mesh': 'D017114'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 1095, 'end': 1108, 'mesh': 'D000082'}, {'text': 'ALF', 'type': 'Disease', 'start': 1117, 'end': 1120, 'mesh': 'D017114'}, {'text': 'CLD', 'type': 'Disease', 'start': 1127, 'end': 1130, 'mesh': 'D008107'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 1353, 'end': 1366, 'mesh': 'D000082'}, {'text': 'ALF', 'type': 'Disease', 'start': 1375, 'end': 1378, 'mesh': 'D017114'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 1408, 'end': 1421, 'mesh': 'D000082'}, {'text': 'ALF', 'type': 'Disease', 'start': 1430, 'end': 1433, 'mesh': 'D017114'}, {'text': 'CLD', 'type': 'Disease', 'start': 1444, 'end': 1447, 'mesh': 'D008107'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 1479, 'end': 1492, 'mesh': 'D000082'}, {'text': 'ALF', 'type': 'Disease', 'start': 1501, 'end': 1504, 'mesh': 'D017114'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 1687, 'end': 1700, 'mesh': 'D000082'}, {'text': 'ALF', 'type': 'Disease', 'start': 1709, 'end': 1712, 'mesh': 'D017114'}, {'text': 'acetaminophen', 'type': 'Chemical', 'start': 1759, 'end': 1772, 'mesh': 'D000082'}, {'text': 'ALF', 'type': 'Disease', 'start': 1781, 'end': 1784, 'mesh': 'D017114'}, {'text': 'CLD', 'type': 'Disease', 'start': 1804, 'end': 1807, 'mesh': 'D008107'}]"
+1488,20447294,"Studies of synergy between morphine and a novel sodium channel blocker, CNSB002, in rat models of inflammatory and neuropathic pain.","OBJECTIVE: This study determined the antihyperalgesic effect of CNSB002, a sodium channel blocker with antioxidant properties given alone and in combinations with morphine in rat models of inflammatory and neuropathic pain. DESIGN: Dose response curves for nonsedating doses of morphine and CNSB002 given intraperitoneally alone and together in combinations were constructed for antihyperalgesic effect using paw withdrawal from noxious heat in two rat pain models: carrageenan-induced paw inflammation and streptozotocin (STZ)-induced diabetic neuropathy. RESULTS: The maximum nonsedating doses were: morphine, 3.2 mg/kg; CNSB002 10.0 mg/kg; 5.0 mg/kg CNSB002 with morphine 3.2 mg/kg in combination. The doses calculated to cause 50% reversal of hyperalgesia (ED50) were 7.54 (1.81) and 4.83 (1.54) in the carrageenan model and 44.18 (1.37) and 9.14 (1.24) in the STZ-induced neuropathy model for CNSB002 and morphine, respectively (mg/kg; mean, SEM). These values were greater than the maximum nonsedating doses. The ED50 values for morphine when given in combination with CNSB002 (5 mg/kg) were less than the maximum nonsedating dose: 0.56 (1.55) in the carrageenan model and 1.37 (1.23) in the neuropathy model (mg/kg; mean, SEM). The antinociception after morphine (3.2 mg/kg) was increased by co-administration with CNSB002 from 28.0 and 31.7% to 114.6 and 56.9% reversal of hyperalgesia in the inflammatory and neuropathic models, respectively (P < 0.01; one-way analysis of variance-significantly greater than either drug given alone). CONCLUSIONS: The maximum antihyperalgesic effect achievable with nonsedating doses of morphine may be increased significantly when the drug is used in combination with CNSB002.","[{'text': 'morphine', 'type': 'Chemical', 'start': 27, 'end': 35, 'mesh': 'D009020'}, {'text': 'sodium', 'type': 'Chemical', 'start': 48, 'end': 54, 'mesh': 'D012964'}, {'text': 'CNSB002', 'type': 'Chemical', 'start': 72, 'end': 79, 'mesh': 'C401121'}, {'text': 'neuropathic pain', 'type': 'Disease', 'start': 115, 'end': 131, 'mesh': 'D009437'}, {'text': 'CNSB002', 'type': 'Chemical', 'start': 197, 'end': 204, 'mesh': 'C401121'}, {'text': 'sodium', 'type': 'Chemical', 'start': 208, 'end': 214, 'mesh': 'D012964'}, {'text': 'morphine', 'type': 'Chemical', 'start': 296, 'end': 304, 'mesh': 'D009020'}, {'text': 'neuropathic pain', 'type': 'Disease', 'start': 339, 'end': 355, 'mesh': 'D009437'}, {'text': 'morphine', 'type': 'Chemical', 'start': 411, 'end': 419, 'mesh': 'D009020'}, {'text': 'CNSB002', 'type': 'Chemical', 'start': 424, 'end': 431, 'mesh': 'C401121'}, {'text': 'pain', 'type': 'Disease', 'start': 586, 'end': 590, 'mesh': 'D010146'}, {'text': 'carrageenan', 'type': 'Chemical', 'start': 599, 'end': 610, 'mesh': 'D002351'}, {'text': 'inflammation', 'type': 'Disease', 'start': 623, 'end': 635, 'mesh': 'D007249'}, {'text': 'streptozotocin', 'type': 'Chemical', 'start': 640, 'end': 654, 'mesh': 'D013311'}, {'text': 'STZ', 'type': 'Chemical', 'start': 656, 'end': 659, 'mesh': 'D013311'}, {'text': 'diabetic neuropathy', 'type': 'Disease', 'start': 669, 'end': 688, 'mesh': 'D003929'}, {'text': 'morphine', 'type': 'Chemical', 'start': 735, 'end': 743, 'mesh': 'D009020'}, {'text': 'CNSB002', 'type': 'Chemical', 'start': 756, 'end': 763, 'mesh': 'C401121'}, {'text': 'CNSB002', 'type': 'Chemical', 'start': 786, 'end': 793, 'mesh': 'C401121'}, {'text': 'morphine', 'type': 'Chemical', 'start': 799, 'end': 807, 'mesh': 'D009020'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 880, 'end': 892, 'mesh': 'D006930'}, {'text': 'carrageenan', 'type': 'Chemical', 'start': 940, 'end': 951, 'mesh': 'D002351'}, {'text': 'STZ', 'type': 'Chemical', 'start': 998, 'end': 1001, 'mesh': 'D013311'}, {'text': 'neuropathy', 'type': 'Disease', 'start': 1010, 'end': 1020, 'mesh': 'D009422'}, {'text': 'CNSB002', 'type': 'Chemical', 'start': 1031, 'end': 1038, 'mesh': 'C401121'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1043, 'end': 1051, 'mesh': 'D009020'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1168, 'end': 1176, 'mesh': 'D009020'}, {'text': 'CNSB002', 'type': 'Chemical', 'start': 1208, 'end': 1215, 'mesh': 'C401121'}, {'text': 'carrageenan', 'type': 'Chemical', 'start': 1290, 'end': 1301, 'mesh': 'D002351'}, {'text': 'neuropathy', 'type': 'Disease', 'start': 1331, 'end': 1341, 'mesh': 'D009422'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1394, 'end': 1402, 'mesh': 'D009020'}, {'text': 'CNSB002', 'type': 'Chemical', 'start': 1455, 'end': 1462, 'mesh': 'C401121'}, {'text': 'hyperalgesia', 'type': 'Disease', 'start': 1514, 'end': 1526, 'mesh': 'D006930'}, {'text': 'neuropathic', 'type': 'Disease', 'start': 1551, 'end': 1562, 'mesh': 'D009422'}, {'text': 'morphine', 'type': 'Chemical', 'start': 1763, 'end': 1771, 'mesh': 'D009020'}, {'text': 'CNSB002', 'type': 'Chemical', 'start': 1845, 'end': 1852, 'mesh': 'C401121'}]"
+1489,20495512,Heparin-induced thrombocytopenia: a practical review.,"Heparin-induced thrombocytopenia (HIT) remains under-recognized despite its potentially devastating outcomes. It begins when heparin exposure stimulates the formation of heparin-platelet factor 4 antibodies, which in turn triggers the release of procoagulant platelet particles. Thrombosis and thrombocytopenia that follow comprise the 2 hallmark traits of HIT, with the former largely responsible for significant vascular complications. The prevalence of HIT varies among several subgroups, with greater incidence in surgical as compared with medical populations. HIT must be acknowledged for its intense predilection for thrombosis and suspected whenever thrombosis occurs after heparin exposure. Early recognition that incorporates the clinical and serologic clues is paramount to timely institution of treatment, as its delay may result in catastrophic outcomes. The treatment of HIT mandates an immediate cessation of all heparin exposure and the institution of an antithrombotic therapy, most commonly using a direct thrombin inhibitor. Current ""diagnostic"" tests, which primarily include functional and antigenic assays, have more of a confirmatory than diagnostic role in the management of HIT. Special attention must be paid to cardiac patients who are often exposed to heparin multiple times during their course of treatment. Direct thrombin inhibitors are appropriate, evidence-based alternatives to heparin in patients with a history of HIT, who need to undergo percutaneous coronary intervention. As heparin remains one of the most frequently used medications today with potential for HIT with every heparin exposure, a close vigilance of platelet counts must be practiced whenever heparin is initiated.","[{'text': 'Heparin', 'type': 'Chemical', 'start': 0, 'end': 7, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 16, 'end': 32, 'mesh': 'D013921'}, {'text': 'Heparin', 'type': 'Chemical', 'start': 54, 'end': 61, 'mesh': 'D006493'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 70, 'end': 86, 'mesh': 'D013921'}, {'text': 'HIT', 'type': 'Disease', 'start': 88, 'end': 91, 'mesh': 'D013921'}, {'text': 'heparin', 'type': 'Chemical', 'start': 179, 'end': 186, 'mesh': 'D006493'}, {'text': 'heparin', 'type': 'Chemical', 'start': 224, 'end': 231, 'mesh': 'D006493'}, {'text': 'Thrombosis', 'type': 'Disease', 'start': 333, 'end': 343, 'mesh': 'D013927'}, {'text': 'thrombocytopenia', 'type': 'Disease', 'start': 348, 'end': 364, 'mesh': 'D013921'}, {'text': 'HIT', 'type': 'Disease', 'start': 411, 'end': 414, 'mesh': 'D013921'}, {'text': 'HIT', 'type': 'Disease', 'start': 510, 'end': 513, 'mesh': 'D013921'}, {'text': 'HIT', 'type': 'Disease', 'start': 619, 'end': 622, 'mesh': 'D013921'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 677, 'end': 687, 'mesh': 'D013927'}, {'text': 'thrombosis', 'type': 'Disease', 'start': 711, 'end': 721, 'mesh': 'D013927'}, {'text': 'heparin', 'type': 'Chemical', 'start': 735, 'end': 742, 'mesh': 'D006493'}, {'text': 'HIT', 'type': 'Disease', 'start': 938, 'end': 941, 'mesh': 'D013921'}, {'text': 'heparin', 'type': 'Chemical', 'start': 981, 'end': 988, 'mesh': 'D006493'}, {'text': 'direct thrombin inhibitor', 'type': 'Chemical', 'start': 1070, 'end': 1095, 'mesh': 'D000991'}, {'text': 'HIT', 'type': 'Disease', 'start': 1252, 'end': 1255, 'mesh': 'D013921'}, {'text': 'heparin', 'type': 'Chemical', 'start': 1333, 'end': 1340, 'mesh': 'D006493'}, {'text': 'Direct thrombin inhibitors', 'type': 'Chemical', 'start': 1390, 'end': 1416, 'mesh': 'D000991'}, {'text': 'heparin', 'type': 'Chemical', 'start': 1465, 'end': 1472, 'mesh': 'D006493'}, {'text': 'HIT', 'type': 'Disease', 'start': 1503, 'end': 1506, 'mesh': 'D013921'}, {'text': 'heparin', 'type': 'Chemical', 'start': 1567, 'end': 1574, 'mesh': 'D006493'}, {'text': 'HIT', 'type': 'Disease', 'start': 1652, 'end': 1655, 'mesh': 'D013921'}, {'text': 'heparin', 'type': 'Chemical', 'start': 1667, 'end': 1674, 'mesh': 'D006493'}, {'text': 'heparin', 'type': 'Chemical', 'start': 1749, 'end': 1756, 'mesh': 'D006493'}]"
+1490,20513036,Abductor paralysis after botox injection for adductor spasmodic dysphonia.,"OBJECTIVES/HYPOTHESIS: Botulinum toxin (Botox) injections into the thyroarytenoid muscles are the current standard of care for adductor spasmodic dysphonia (ADSD). Reported adverse effects include a period of breathiness, throat pain, and difficulty with swallowing liquids. Here we report multiple cases of bilateral abductor paralysis following Botox injections for ADSD, a complication previously unreported. STUDY DESIGN: Retrospective case series. METHODS: Patients that received Botox injections for spasmodic dysphonia between January 2000 and October 2009 were evaluated. Patients with ADSD were identified. The number of treatments received and adverse effects were noted. For patients with bilateral abductor paralysis, age, sex, paralytic Botox dose, prior Botox dose, and course following paralysis were noted. RESULTS: From a database of 452 patients receiving Botox, 352 patients had been diagnosed with ADSD. Of these 352 patients, eight patients suffered bilateral abductor paralysis, and two suffered this complication twice. All affected patients were females over the age of 50 years. Most patients had received treatments prior to abductor paralysis and continued receiving after paralysis. Seven patients recovered after a brief period of activity restrictions, and one underwent a tracheotomy. The incidence of abductor paralysis after Botox injection for ADSD was 0.34%. CONCLUSIONS: Bilateral abductor paralysis is a rare complication of Botox injections for ADSD, causing difficulty with breathing upon exertion. The likely mechanism of paralysis is diffusion of Botox around the muscular process of the arytenoid to the posterior cricoarytenoid muscles. The paralysis is temporary, and watchful waiting with restriction of activity is the recommended management.","[{'text': 'paralysis', 'type': 'Disease', 'start': 9, 'end': 18, 'mesh': 'D010243'}, {'text': 'botox', 'type': 'Chemical', 'start': 25, 'end': 30, 'mesh': 'C542870'}, {'text': 'adductor spasmodic dysphonia', 'type': 'Disease', 'start': 45, 'end': 73, 'mesh': 'D014826'}, {'text': 'Botox', 'type': 'Chemical', 'start': 115, 'end': 120, 'mesh': 'C542870'}, {'text': 'adductor spasmodic dysphonia', 'type': 'Disease', 'start': 202, 'end': 230, 'mesh': 'D014826'}, {'text': 'ADSD', 'type': 'Disease', 'start': 232, 'end': 236, 'mesh': 'D014826'}, {'text': 'throat pain', 'type': 'Disease', 'start': 297, 'end': 308, 'mesh': 'D010612'}, {'text': 'paralysis', 'type': 'Disease', 'start': 402, 'end': 411, 'mesh': 'D010243'}, {'text': 'Botox', 'type': 'Chemical', 'start': 422, 'end': 427, 'mesh': 'C542870'}, {'text': 'ADSD', 'type': 'Disease', 'start': 443, 'end': 447, 'mesh': 'D014826'}, {'text': 'Botox', 'type': 'Chemical', 'start': 560, 'end': 565, 'mesh': 'C542870'}, {'text': 'spasmodic dysphonia', 'type': 'Disease', 'start': 581, 'end': 600, 'mesh': 'D055154'}, {'text': 'ADSD', 'type': 'Disease', 'start': 669, 'end': 673, 'mesh': 'D014826'}, {'text': 'paralysis', 'type': 'Disease', 'start': 794, 'end': 803, 'mesh': 'D010243'}, {'text': 'Botox', 'type': 'Chemical', 'start': 825, 'end': 830, 'mesh': 'C542870'}, {'text': 'Botox', 'type': 'Chemical', 'start': 843, 'end': 848, 'mesh': 'C542870'}, {'text': 'paralysis', 'type': 'Disease', 'start': 876, 'end': 885, 'mesh': 'D010243'}, {'text': 'Botox', 'type': 'Chemical', 'start': 949, 'end': 954, 'mesh': 'C542870'}, {'text': 'ADSD', 'type': 'Disease', 'start': 993, 'end': 997, 'mesh': 'D014826'}, {'text': 'paralysis', 'type': 'Disease', 'start': 1065, 'end': 1074, 'mesh': 'D010243'}, {'text': 'paralysis', 'type': 'Disease', 'start': 1235, 'end': 1244, 'mesh': 'D010243'}, {'text': 'paralysis', 'type': 'Disease', 'start': 1275, 'end': 1284, 'mesh': 'D010243'}, {'text': 'paralysis', 'type': 'Disease', 'start': 1417, 'end': 1426, 'mesh': 'D010243'}, {'text': 'Botox', 'type': 'Chemical', 'start': 1433, 'end': 1438, 'mesh': 'C542870'}, {'text': 'ADSD', 'type': 'Disease', 'start': 1453, 'end': 1457, 'mesh': 'D014826'}, {'text': 'paralysis', 'type': 'Disease', 'start': 1501, 'end': 1510, 'mesh': 'D010243'}, {'text': 'Botox', 'type': 'Chemical', 'start': 1537, 'end': 1542, 'mesh': 'C542870'}, {'text': 'ADSD', 'type': 'Disease', 'start': 1558, 'end': 1562, 'mesh': 'D014826'}, {'text': 'paralysis', 'type': 'Disease', 'start': 1637, 'end': 1646, 'mesh': 'D010243'}, {'text': 'Botox', 'type': 'Chemical', 'start': 1663, 'end': 1668, 'mesh': 'C542870'}, {'text': 'paralysis', 'type': 'Disease', 'start': 1759, 'end': 1768, 'mesh': 'D010243'}]"
+1491,20566328,Mitochondrial impairment contributes to cocaine-induced cardiac dysfunction: Prevention by the targeted antioxidant MitoQ.,"The goal of this study was to assess mitochondrial function and ROS production in an experimental model of cocaine-induced cardiac dysfunction. We hypothesized that cocaine abuse may lead to altered mitochondrial function that in turn may cause left ventricular dysfunction. Seven days of cocaine administration to rats led to an increased oxygen consumption detected in cardiac fibers, specifically through complex I and complex III. ROS levels were increased, specifically in interfibrillar mitochondria. In parallel there was a decrease in ATP synthesis, whereas no difference was observed in subsarcolemmal mitochondria. This uncoupling effect on oxidative phosphorylation was not detectable after short-term exposure to cocaine, suggesting that these mitochondrial abnormalities were a late rather than a primary event in the pathological response to cocaine. MitoQ, a mitochondrial-targeted antioxidant, was shown to completely prevent these mitochondrial abnormalities as well as cardiac dysfunction characterized here by a diastolic dysfunction studied with a conductance catheter to obtain pressure-volume data. Taken together, these results extend previous studies and demonstrate that cocaine-induced cardiac dysfunction may be due to a mitochondrial defect.","[{'text': 'Mitochondrial impairment', 'type': 'Disease', 'start': 0, 'end': 24, 'mesh': 'D028361'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 40, 'end': 47, 'mesh': 'D003042'}, {'text': 'cardiac dysfunction', 'type': 'Disease', 'start': 56, 'end': 75, 'mesh': 'D006331'}, {'text': 'MitoQ', 'type': 'Chemical', 'start': 116, 'end': 121, 'mesh': 'C476756'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 230, 'end': 237, 'mesh': 'D003042'}, {'text': 'cardiac dysfunction', 'type': 'Disease', 'start': 246, 'end': 265, 'mesh': 'D006331'}, {'text': 'cocaine abuse', 'type': 'Disease', 'start': 288, 'end': 301, 'mesh': 'D019970'}, {'text': 'left ventricular dysfunction', 'type': 'Disease', 'start': 368, 'end': 396, 'mesh': 'D018487'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 412, 'end': 419, 'mesh': 'D003042'}, {'text': 'oxygen', 'type': 'Chemical', 'start': 463, 'end': 469, 'mesh': 'D010100'}, {'text': 'ATP', 'type': 'Chemical', 'start': 666, 'end': 669, 'mesh': 'D000255'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 848, 'end': 855, 'mesh': 'D003042'}, {'text': 'mitochondrial abnormalities', 'type': 'Disease', 'start': 879, 'end': 906, 'mesh': 'D028361'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 979, 'end': 986, 'mesh': 'D003042'}, {'text': 'MitoQ', 'type': 'Chemical', 'start': 988, 'end': 993, 'mesh': 'C476756'}, {'text': 'mitochondrial abnormalities', 'type': 'Disease', 'start': 1071, 'end': 1098, 'mesh': 'D028361'}, {'text': 'cardiac dysfunction', 'type': 'Disease', 'start': 1110, 'end': 1129, 'mesh': 'D006331'}, {'text': 'diastolic dysfunction', 'type': 'Disease', 'start': 1154, 'end': 1175, 'mesh': '-1'}, {'text': 'cocaine', 'type': 'Chemical', 'start': 1319, 'end': 1326, 'mesh': 'D003042'}, {'text': 'cardiac dysfunction', 'type': 'Disease', 'start': 1335, 'end': 1354, 'mesh': 'D006331'}, {'text': 'mitochondrial defect', 'type': 'Disease', 'start': 1371, 'end': 1391, 'mesh': 'D028361'}]"
+1492,20589632,Trimethoprim-induced immune hemolytic anemia in a pediatric oncology patient presenting as an acute hemolytic transfusion reaction.,"A 10-year-old male with acute leukemia presented with post-chemotherapy anemia. During red cell transfusion, he developed hemoglobinuria. Transfusion reaction workup was negative. Drug-induced immune hemolytic anemia was suspected because of positive direct antiglobulin test, negative eluate, and microspherocytes on smear pre- and post-transfusion. Drug studies using the indirect antiglobulin test were strongly positive with trimethoprim and trimethoprim-sulfamethoxazole but negative with sulfamethoxazole. The patient recovered after discontinuing the drug, with no recurrence in 2 years. Other causes of anemia should be considered in patients with worse-than-expected anemia after chemotherapy. Furthermore, hemolysis during transfusion is not always a transfusion reaction.","[{'text': 'Trimethoprim', 'type': 'Chemical', 'start': 0, 'end': 12, 'mesh': 'D014295'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 28, 'end': 44, 'mesh': 'D000743'}, {'text': 'acute leukemia', 'type': 'Disease', 'start': 156, 'end': 170, 'mesh': 'D015470'}, {'text': 'anemia', 'type': 'Disease', 'start': 204, 'end': 210, 'mesh': 'D000740'}, {'text': 'hemoglobinuria', 'type': 'Disease', 'start': 254, 'end': 268, 'mesh': 'D006456'}, {'text': 'hemolytic anemia', 'type': 'Disease', 'start': 332, 'end': 348, 'mesh': 'D000743'}, {'text': 'trimethoprim', 'type': 'Chemical', 'start': 561, 'end': 573, 'mesh': 'D014295'}, {'text': 'trimethoprim-sulfamethoxazole', 'type': 'Chemical', 'start': 578, 'end': 607, 'mesh': 'D015662'}, {'text': 'sulfamethoxazole', 'type': 'Chemical', 'start': 626, 'end': 642, 'mesh': 'D013420'}, {'text': 'anemia', 'type': 'Disease', 'start': 743, 'end': 749, 'mesh': 'D000740'}, {'text': 'anemia', 'type': 'Disease', 'start': 808, 'end': 814, 'mesh': 'D000740'}, {'text': 'hemolysis', 'type': 'Disease', 'start': 848, 'end': 857, 'mesh': 'D006461'}]"
+1493,20682692,Blockade of endothelial-mesenchymal transition by a Smad3 inhibitor delays the early development of streptozotocin-induced diabetic nephropathy.,"OBJECTIVE: A multicenter, controlled trial showed that early blockade of the renin-angiotensin system in patients with type 1 diabetes and normoalbuminuria did not retard the progression of nephropathy, suggesting that other mechanism(s) are involved in the pathogenesis of early diabetic nephropathy (diabetic nephropathy). We have previously demonstrated that endothelial-mesenchymal-transition (EndoMT) contributes to the early development of renal interstitial fibrosis independently of microalbuminuria in mice with streptozotocin (STZ)-induced diabetes. In the present study, we hypothesized that blocking EndoMT reduces the early development of diabetic nephropathy. RESEARCH DESIGN AND METHODS: EndoMT was induced in a mouse pancreatic microvascular endothelial cell line (MMEC) in the presence of advanced glycation end products (AGEs) and in the endothelial lineage-traceble mouse line Tie2-Cre;Loxp-EGFP by administration of AGEs, with nonglycated mouse albumin serving as a control. Phosphorylated Smad3 was detected by immunoprecipitation/Western blotting and confocal microscopy. Blocking studies using receptor for AGE siRNA and a specific inhibitor of Smad3 (SIS3) were performed in MMECs and in STZ-induced diabetic nephropathy in Tie2-Cre;Loxp-EGFP mice. RESULTS: Confocal microscopy and real-time PCR demonstrated that AGEs induced EndoMT in MMECs and in Tie2-Cre;Loxp-EGFP mice. Immunoprecipitation/Western blotting showed that Smad3 was activated by AGEs but was inhibited by SIS3 in MMECs and in STZ-induced diabetic nephropathy. Confocal microscopy and real-time PCR further demonstrated that SIS3 abrogated EndoMT, reduced renal fibrosis, and retarded progression of nephropathy. CONCLUSIONS: EndoMT is a novel pathway leading to early development of diabetic nephropathy. Blockade of EndoMT by SIS3 may provide a new strategy to retard the progression of diabetic nephropathy and other diabetes complications.","[{'text': 'streptozotocin', 'type': 'Chemical', 'start': 100, 'end': 114, 'mesh': 'D013311'}, {'text': 'diabetic nephropathy', 'type': 'Disease', 'start': 123, 'end': 143, 'mesh': 'D003928'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 228, 'end': 239, 'mesh': 'D000804'}, {'text': 'type 1 diabetes', 'type': 'Disease', 'start': 264, 'end': 279, 'mesh': 'D003922'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 335, 'end': 346, 'mesh': 'D007674'}, {'text': 'diabetic nephropathy', 'type': 'Disease', 'start': 425, 'end': 445, 'mesh': 'D003928'}, {'text': 'diabetic nephropathy', 'type': 'Disease', 'start': 447, 'end': 467, 'mesh': 'D003928'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 610, 'end': 618, 'mesh': 'D005355'}, {'text': 'streptozotocin', 'type': 'Chemical', 'start': 666, 'end': 680, 'mesh': 'D013311'}, {'text': 'STZ', 'type': 'Chemical', 'start': 682, 'end': 685, 'mesh': 'D013311'}, {'text': 'diabetes', 'type': 'Disease', 'start': 695, 'end': 703, 'mesh': 'D003920'}, {'text': 'diabetic nephropathy', 'type': 'Disease', 'start': 797, 'end': 817, 'mesh': 'D003928'}, {'text': 'STZ', 'type': 'Chemical', 'start': 1357, 'end': 1360, 'mesh': 'D013311'}, {'text': 'diabetic nephropathy', 'type': 'Disease', 'start': 1369, 'end': 1389, 'mesh': 'D003928'}, {'text': 'STZ', 'type': 'Chemical', 'start': 1663, 'end': 1666, 'mesh': 'D013311'}, {'text': 'diabetic nephropathy', 'type': 'Disease', 'start': 1675, 'end': 1695, 'mesh': 'D003928'}, {'text': 'fibrosis', 'type': 'Disease', 'start': 1798, 'end': 1806, 'mesh': 'D005355'}, {'text': 'nephropathy', 'type': 'Disease', 'start': 1836, 'end': 1847, 'mesh': 'D007674'}, {'text': 'diabetic nephropathy', 'type': 'Disease', 'start': 1920, 'end': 1940, 'mesh': 'D003928'}, {'text': 'diabetic nephropathy', 'type': 'Disease', 'start': 2025, 'end': 2045, 'mesh': 'D003928'}, {'text': 'diabetes complications', 'type': 'Disease', 'start': 2056, 'end': 2078, 'mesh': 'D048909'}]"
+1494,20828385,Cytostatic and anti-angiogenic effects of temsirolimus in refractory mantle cell lymphoma.,"Mantle cell lymphoma (MCL) is a rare and aggressive type of B-cell non-Hodgkin's lymphoma. Patients become progressively refractory to conventional chemotherapy, and their prognosis is poor. However, a 38% remission rate has been recently reported in refractory MCL treated with temsirolimus, a mTOR inhibitor.Here we had the opportunity to study a case of refractory MCL who had tumor regression two months after temsirolimus treatment, and a progression-free survival of 10 months. In this case, lymph node biopsies were performed before and six months after temsirolimus therapy. Comparison of the two biopsies showed that temsirolimus inhibited tumor cell proliferation through cell cycle arrest, but did not induce any change in the number of apoptotic tumor cells. Apart from this cytostatic effect, temsirolimus had an antiangiogenic effect with decrease of tumor microvessel density and of VEGF expression. Moreover, numerous patchy, well-limited fibrotic areas, compatible with post-necrotic tissue repair, were found after 6-month temsirolimus therapy. Thus, temsirolimus reduced tumor burden through associated cytostatic and anti-angiogenic effects.This dual effect of temsirolimus on tumor tissue could contribute to its recently reported efficiency in refractory MCL resistant to conventional chemotherapy.","[{'text': 'temsirolimus', 'type': 'Chemical', 'start': 42, 'end': 54, 'mesh': 'C401859'}, {'text': 'mantle cell lymphoma', 'type': 'Disease', 'start': 69, 'end': 89, 'mesh': 'D020522'}, {'text': 'Mantle cell lymphoma', 'type': 'Disease', 'start': 91, 'end': 111, 'mesh': 'D020522'}, {'text': 'MCL', 'type': 'Disease', 'start': 113, 'end': 116, 'mesh': 'D020522'}, {'text': ""B-cell non-Hodgkin's lymphoma"", 'type': 'Disease', 'start': 151, 'end': 180, 'mesh': 'D008228'}, {'text': 'MCL', 'type': 'Disease', 'start': 353, 'end': 356, 'mesh': 'D020522'}, {'text': 'temsirolimus', 'type': 'Chemical', 'start': 370, 'end': 382, 'mesh': 'C401859'}, {'text': 'MCL', 'type': 'Disease', 'start': 459, 'end': 462, 'mesh': 'D020522'}, {'text': 'tumor', 'type': 'Disease', 'start': 471, 'end': 476, 'mesh': 'D009369'}, {'text': 'temsirolimus', 'type': 'Chemical', 'start': 505, 'end': 517, 'mesh': 'C401859'}, {'text': 'temsirolimus', 'type': 'Chemical', 'start': 652, 'end': 664, 'mesh': 'C401859'}, {'text': 'temsirolimus', 'type': 'Chemical', 'start': 717, 'end': 729, 'mesh': 'C401859'}, {'text': 'tumor', 'type': 'Disease', 'start': 740, 'end': 745, 'mesh': 'D009369'}, {'text': 'tumor', 'type': 'Disease', 'start': 849, 'end': 854, 'mesh': 'D009369'}, {'text': 'temsirolimus', 'type': 'Chemical', 'start': 897, 'end': 909, 'mesh': 'C401859'}, {'text': 'tumor', 'type': 'Disease', 'start': 956, 'end': 961, 'mesh': 'D009369'}, {'text': 'necrotic', 'type': 'Disease', 'start': 1083, 'end': 1091, 'mesh': 'D009336'}, {'text': 'temsirolimus', 'type': 'Chemical', 'start': 1132, 'end': 1144, 'mesh': 'C401859'}, {'text': 'temsirolimus', 'type': 'Chemical', 'start': 1160, 'end': 1172, 'mesh': 'C401859'}, {'text': 'tumor', 'type': 'Disease', 'start': 1181, 'end': 1186, 'mesh': 'D009369'}, {'text': 'temsirolimus', 'type': 'Chemical', 'start': 1272, 'end': 1284, 'mesh': 'C401859'}, {'text': 'tumor', 'type': 'Disease', 'start': 1288, 'end': 1293, 'mesh': 'D009369'}, {'text': 'MCL', 'type': 'Disease', 'start': 1368, 'end': 1371, 'mesh': 'D020522'}]"
+1495,20859899,Syncope caused by hyperkalemia during use of a combined therapy with the angiotensin-converting enzyme inhibitor and spironolactone.,"A 76 year-old woman with a history of coronary artery bypass grafting and prior myocardial infarction was transferred to the emergency room with loss of consciousness due to marked bradycardia caused by hyperkalemia. The concentration of serum potassium was high, and normal sinus rhythm was restored after correction of the serum potassium level. The cause of hyperkalemia was considered to be several doses of spiranolactone, an aldosterone antagonist, in addition to the long-term intake of ramipril, an ACE inhibitor. This case is a good example of electrolyte imbalance causing acute life-threatening cardiac events. Clinicians should be alert to the possibility of hyperkalemia, especially in elderly patients using ACE/ARB in combination with potassium sparing agents and who have mild renal disturbance.","[{'text': 'Syncope', 'type': 'Disease', 'start': 0, 'end': 7, 'mesh': 'D013575'}, {'text': 'hyperkalemia', 'type': 'Disease', 'start': 18, 'end': 30, 'mesh': 'D006947'}, {'text': 'angiotensin', 'type': 'Chemical', 'start': 73, 'end': 84, 'mesh': 'D000809'}, {'text': 'spironolactone', 'type': 'Chemical', 'start': 117, 'end': 131, 'mesh': 'D013148'}, {'text': 'myocardial infarction', 'type': 'Disease', 'start': 213, 'end': 234, 'mesh': 'D009203'}, {'text': 'loss of consciousness', 'type': 'Disease', 'start': 278, 'end': 299, 'mesh': 'D014474'}, {'text': 'bradycardia', 'type': 'Disease', 'start': 314, 'end': 325, 'mesh': 'D001919'}, {'text': 'hyperkalemia', 'type': 'Disease', 'start': 336, 'end': 348, 'mesh': 'D006947'}, {'text': 'potassium', 'type': 'Chemical', 'start': 377, 'end': 386, 'mesh': 'D011188'}, {'text': 'potassium', 'type': 'Chemical', 'start': 464, 'end': 473, 'mesh': 'D011188'}, {'text': 'hyperkalemia', 'type': 'Disease', 'start': 494, 'end': 506, 'mesh': 'D006947'}, {'text': 'spiranolactone', 'type': 'Chemical', 'start': 545, 'end': 559, 'mesh': 'D013148'}, {'text': 'aldosterone', 'type': 'Chemical', 'start': 564, 'end': 575, 'mesh': 'D000450'}, {'text': 'ramipril', 'type': 'Chemical', 'start': 627, 'end': 635, 'mesh': 'D017257'}, {'text': 'hyperkalemia', 'type': 'Disease', 'start': 804, 'end': 816, 'mesh': 'D006947'}, {'text': 'potassium', 'type': 'Chemical', 'start': 883, 'end': 892, 'mesh': 'D011188'}, {'text': 'renal disturbance', 'type': 'Disease', 'start': 926, 'end': 943, 'mesh': 'D007674'}]"
+1496,20927253,Diffuse skeletal pain after administration of alendronate.,"BACKGROUND: Osteoporosis is caused by bone resorption in excess of bone formation, and bisphosphonates, are used to inhibit bone resorption. Alendronate, a biphosphonate, is effective for both the treatment and prevention of osteoporosis in postmenopausal women. Side effects are relatively few and prominently gastrointestinal. Musculoskeletal pain may be an important side effect in these patients. We presented a patient admitted to our out-patient clinic with diffuse skeletal pain after three consecutive administration of alendronate. CONCLUSION: We conclude that patients with osteoporosis can report pain, and bisphosphonate-related pain should also be considered before ascribing this complaint to osteoporosis.","[{'text': 'pain', 'type': 'Disease', 'start': 17, 'end': 21, 'mesh': 'D010146'}, {'text': 'alendronate', 'type': 'Chemical', 'start': 46, 'end': 57, 'mesh': 'D019386'}, {'text': 'Osteoporosis', 'type': 'Disease', 'start': 71, 'end': 83, 'mesh': 'D010024'}, {'text': 'bisphosphonates', 'type': 'Chemical', 'start': 146, 'end': 161, 'mesh': 'D004164'}, {'text': 'Alendronate', 'type': 'Chemical', 'start': 200, 'end': 211, 'mesh': 'D019386'}, {'text': 'biphosphonate', 'type': 'Chemical', 'start': 215, 'end': 228, 'mesh': '-1'}, {'text': 'osteoporosis', 'type': 'Disease', 'start': 284, 'end': 296, 'mesh': 'D010024'}, {'text': 'Musculoskeletal pain', 'type': 'Disease', 'start': 388, 'end': 408, 'mesh': 'D059352'}, {'text': 'pain', 'type': 'Disease', 'start': 540, 'end': 544, 'mesh': 'D010146'}, {'text': 'alendronate', 'type': 'Chemical', 'start': 587, 'end': 598, 'mesh': 'D019386'}, {'text': 'osteoporosis', 'type': 'Disease', 'start': 643, 'end': 655, 'mesh': 'D010024'}, {'text': 'pain', 'type': 'Disease', 'start': 667, 'end': 671, 'mesh': 'D010146'}, {'text': 'bisphosphonate', 'type': 'Chemical', 'start': 677, 'end': 691, 'mesh': 'D004164'}, {'text': 'pain', 'type': 'Disease', 'start': 700, 'end': 704, 'mesh': 'D010146'}, {'text': 'osteoporosis', 'type': 'Disease', 'start': 766, 'end': 778, 'mesh': 'D010024'}]"
+1497,20959502,Cerebrospinal fluid penetration of high-dose daptomycin in suspected Staphylococcus aureus meningitis.,"OBJECTIVE: To report a case of methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia with suspected MSSA meningitis treated with high-dose daptomycin assessed with concurrent serum and cerebrospinal fluid (CSF) concentrations. CASE SUMMARY: A 54-year-old male presented to the emergency department with generalized weakness and presumed health-care-associated pneumonia shown on chest radiograph. Treatment was empirically initiated with vancomycin, levofloxacin, and piperacillin/tazobactam. Blood cultures revealed S. aureus susceptible to oxacillin. Empiric antibiotic treatment was narrowed to nafcillin on day 4. On day 8, the patient developed acute renal failure (serum creatinine 1.9 mg/dL, increased from 1.2 mg/dL the previous day and 0.8 mg/dL on admission). The patient's Glasgow Coma Score was 3, with normal findings shown on computed tomography scan of the head 72 hours following an episode of cardiac arrest on day 10. The patient experienced relapsing MSSA bacteremia on day 9, increasing the suspicion for a central nervous system (CNS) infection. Nafcillin was discontinued and daptomycin 9 mg/kg daily was initiated for suspected meningitis and was continued until the patient's death on day 16. Daptomycin serum and CSF trough concentrations were 11.21 ug/mL and 0.52 ug/mL, respectively, prior to the third dose. Lumbar puncture results were inconclusive and no further blood cultures were positive for MSSA. Creatine kinase levels were normal prior to daptomycin therapy and were not reassessed. DISCUSSION: Daptomycin was initiated in our patient secondary to possible nafcillin-induced acute interstitial nephritis and relapsing bacteremia. At a dose of 9 mg/kg, resultant penetration of 5% was higher than in previous reports, more consistent with inflamed meninges. CONCLUSIONS: High-dose daptomycin may be an alternative option for MSSA bacteremia with or without a CNS source in patients who have failed or cannot tolerate standard therapy. Further clinical evaluation in patients with confirmed meningitis is warranted.","[{'text': 'daptomycin', 'type': 'Chemical', 'start': 45, 'end': 55, 'mesh': 'D017576'}, {'text': 'meningitis', 'type': 'Disease', 'start': 91, 'end': 101, 'mesh': 'D008581'}, {'text': 'methicillin', 'type': 'Chemical', 'start': 134, 'end': 145, 'mesh': 'D008712'}, {'text': 'bacteremia', 'type': 'Disease', 'start': 185, 'end': 195, 'mesh': 'D016470'}, {'text': 'meningitis', 'type': 'Disease', 'start': 216, 'end': 226, 'mesh': 'D008581'}, {'text': 'daptomycin', 'type': 'Chemical', 'start': 250, 'end': 260, 'mesh': 'D017576'}, {'text': 'weakness', 'type': 'Disease', 'start': 426, 'end': 434, 'mesh': 'D018908'}, {'text': 'pneumonia', 'type': 'Disease', 'start': 471, 'end': 480, 'mesh': 'D011014'}, {'text': 'vancomycin', 'type': 'Chemical', 'start': 549, 'end': 559, 'mesh': 'D014640'}, {'text': 'levofloxacin', 'type': 'Chemical', 'start': 561, 'end': 573, 'mesh': 'D064704'}, {'text': 'piperacillin', 'type': 'Chemical', 'start': 579, 'end': 591, 'mesh': 'D010878'}, {'text': 'tazobactam', 'type': 'Chemical', 'start': 592, 'end': 602, 'mesh': 'C043265'}, {'text': 'oxacillin', 'type': 'Chemical', 'start': 653, 'end': 662, 'mesh': 'D010068'}, {'text': 'nafcillin', 'type': 'Chemical', 'start': 709, 'end': 718, 'mesh': 'D009254'}, {'text': 'acute renal failure', 'type': 'Disease', 'start': 761, 'end': 780, 'mesh': 'D058186'}, {'text': 'creatinine', 'type': 'Chemical', 'start': 788, 'end': 798, 'mesh': 'D003404'}, {'text': 'cardiac arrest', 'type': 'Disease', 'start': 1021, 'end': 1035, 'mesh': 'D006323'}, {'text': 'bacteremia', 'type': 'Disease', 'start': 1086, 'end': 1096, 'mesh': 'D016470'}, {'text': 'infection', 'type': 'Disease', 'start': 1167, 'end': 1176, 'mesh': 'D007239'}, {'text': 'Nafcillin', 'type': 'Chemical', 'start': 1178, 'end': 1187, 'mesh': 'D009254'}, {'text': 'daptomycin', 'type': 'Chemical', 'start': 1209, 'end': 1219, 'mesh': 'D017576'}, {'text': 'meningitis', 'type': 'Disease', 'start': 1262, 'end': 1272, 'mesh': 'D008581'}, {'text': 'Daptomycin', 'type': 'Chemical', 'start': 1328, 'end': 1338, 'mesh': 'D017576'}, {'text': 'Creatine', 'type': 'Chemical', 'start': 1543, 'end': 1551, 'mesh': 'D003401'}, {'text': 'daptomycin', 'type': 'Chemical', 'start': 1587, 'end': 1597, 'mesh': 'D017576'}, {'text': 'Daptomycin', 'type': 'Chemical', 'start': 1643, 'end': 1653, 'mesh': 'D017576'}, {'text': 'nafcillin', 'type': 'Chemical', 'start': 1705, 'end': 1714, 'mesh': 'D009254'}, {'text': 'interstitial nephritis', 'type': 'Disease', 'start': 1729, 'end': 1751, 'mesh': 'D009395'}, {'text': 'bacteremia', 'type': 'Disease', 'start': 1766, 'end': 1776, 'mesh': 'D016470'}, {'text': 'daptomycin', 'type': 'Chemical', 'start': 1928, 'end': 1938, 'mesh': 'D017576'}, {'text': 'bacteremia', 'type': 'Disease', 'start': 1977, 'end': 1987, 'mesh': 'D016470'}, {'text': 'meningitis', 'type': 'Disease', 'start': 2137, 'end': 2147, 'mesh': 'D008581'}]"
+1498,21195121,The role of nitric oxide in convulsions induced by lindane in rats.,"Lindane is an organochloride pesticide and scabicide. It evokes convulsions mainly trough the blockage of GABA(A) receptors. Nitric oxide (NO), gaseous neurotransmitter, has contradictor role in epileptogenesis due to opposite effects of L-arginine, precursor of NO syntheses (NOS), and L-NAME (NOS inhibitor) observed in different epilepsy models. The aim of the current study was to determine the effects of NO on the behavioral and EEG characteristics of lindane-induced epilepsy in male Wistar albino rats. The administration of L-arginine (600, 800 and 1000 mg/kg, i.p.) in dose-dependent manner significantly increased convulsion incidence and severity and shortened latency time to first convulsion elicited by lower lindane dose (4 mg/kg, i.p.). On the contrary, pretreatment with L-NAME (500, 700 and 900 mg/kg, i.p.) decreased convulsion incidence and severity and prolonged latency time to convulsion following injection with a convulsive dose of lindane (8 mg/kg, i.p.). EEG analyses showed increase of number and duration of ictal periods in EEG of rats receiving l-arginine prior to lindane and decrease of this number in rats pretreated with L-NAME. These results support the conclusion that NO plays a role of endogenous convulsant in rat model of lindane seizures.","[{'text': 'nitric oxide', 'type': 'Chemical', 'start': 12, 'end': 24, 'mesh': 'D009569'}, {'text': 'convulsions', 'type': 'Disease', 'start': 28, 'end': 39, 'mesh': 'D012640'}, {'text': 'lindane', 'type': 'Chemical', 'start': 51, 'end': 58, 'mesh': 'D001556'}, {'text': 'Lindane', 'type': 'Chemical', 'start': 68, 'end': 75, 'mesh': 'D001556'}, {'text': 'convulsions', 'type': 'Disease', 'start': 132, 'end': 143, 'mesh': 'D012640'}, {'text': 'GABA', 'type': 'Chemical', 'start': 174, 'end': 178, 'mesh': 'D005680'}, {'text': 'Nitric oxide', 'type': 'Chemical', 'start': 193, 'end': 205, 'mesh': 'D009569'}, {'text': 'NO', 'type': 'Chemical', 'start': 207, 'end': 209, 'mesh': 'D009569'}, {'text': 'L-arginine', 'type': 'Chemical', 'start': 306, 'end': 316, 'mesh': 'D001120'}, {'text': 'NO', 'type': 'Chemical', 'start': 331, 'end': 333, 'mesh': 'D009569'}, {'text': 'L-NAME', 'type': 'Chemical', 'start': 355, 'end': 361, 'mesh': 'D019331'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 400, 'end': 408, 'mesh': 'D004827'}, {'text': 'NO', 'type': 'Chemical', 'start': 478, 'end': 480, 'mesh': 'D009569'}, {'text': 'lindane', 'type': 'Chemical', 'start': 526, 'end': 533, 'mesh': 'D001556'}, {'text': 'epilepsy', 'type': 'Disease', 'start': 542, 'end': 550, 'mesh': 'D004827'}, {'text': 'L-arginine', 'type': 'Chemical', 'start': 601, 'end': 611, 'mesh': 'D001120'}, {'text': 'convulsion', 'type': 'Disease', 'start': 693, 'end': 703, 'mesh': 'D012640'}, {'text': 'convulsion', 'type': 'Disease', 'start': 763, 'end': 773, 'mesh': 'D012640'}, {'text': 'lindane', 'type': 'Chemical', 'start': 792, 'end': 799, 'mesh': 'D001556'}, {'text': 'L-NAME', 'type': 'Chemical', 'start': 857, 'end': 863, 'mesh': 'D019331'}, {'text': 'convulsion', 'type': 'Disease', 'start': 905, 'end': 915, 'mesh': 'D012640'}, {'text': 'convulsion', 'type': 'Disease', 'start': 969, 'end': 979, 'mesh': 'D012640'}, {'text': 'convulsive', 'type': 'Disease', 'start': 1007, 'end': 1017, 'mesh': 'D012640'}, {'text': 'lindane', 'type': 'Chemical', 'start': 1026, 'end': 1033, 'mesh': 'D001556'}, {'text': 'l-arginine', 'type': 'Chemical', 'start': 1145, 'end': 1155, 'mesh': 'D001120'}, {'text': 'lindane', 'type': 'Chemical', 'start': 1165, 'end': 1172, 'mesh': 'D001556'}, {'text': 'L-NAME', 'type': 'Chemical', 'start': 1225, 'end': 1231, 'mesh': 'D019331'}, {'text': 'NO', 'type': 'Chemical', 'start': 1275, 'end': 1277, 'mesh': 'D009569'}, {'text': 'lindane', 'type': 'Chemical', 'start': 1332, 'end': 1339, 'mesh': 'D001556'}, {'text': 'seizures', 'type': 'Disease', 'start': 1340, 'end': 1348, 'mesh': 'D012640'}]"
+1499,24055495,Long-term oral galactose treatment prevents cognitive deficits in male Wistar rats treated intracerebroventricularly with streptozotocin.,"Basic and clinical research has demonstrated that dementia of sporadic Alzheimer's disease (sAD) type is associated with dysfunction of the insulin-receptor (IR) system followed by decreased glucose transport via glucose transporter GLUT4 and decreased glucose metabolism in brain cells. An alternative source of energy is d-galactose (the C-4-epimer of d-glucose) which is transported into the brain by insulin-independent GLUT3 transporter where it might be metabolized to glucose via the Leloir pathway. Exclusively parenteral daily injections of galactose induce memory deterioration in rodents and are used to generate animal aging model, but the effects of oral galactose treatment on cognitive functions have never been tested. We have investigated the effects of continuous daily oral galactose (200 mg/kg/day) treatment on cognitive deficits in streptozotocin-induced (STZ-icv) rat model of sAD, tested by Morris Water Maze and Passive Avoidance test, respectively. One month of oral galactose treatment initiated immediately after the STZ-icv administration, successfully prevented development of the STZ-icv-induced cognitive deficits. Beneficial effect of oral galactose was independent of the rat age and of the galactose dose ranging from 100 to 300 mg/kg/day. Additionally, oral galactose administration led to the appearance of galactose in the blood. The increase of galactose concentration in the cerebrospinal fluid was several times lower after oral than after parenteral administration of the same galactose dose. Oral galactose exposure might have beneficial effects on learning and memory ability and could be worth investigating for improvement of cognitive deficits associated with glucose hypometabolism in AD.","[{'text': 'galactose', 'type': 'Chemical', 'start': 15, 'end': 24, 'mesh': 'D005690'}, {'text': 'cognitive deficits', 'type': 'Disease', 'start': 44, 'end': 62, 'mesh': 'D003072'}, {'text': 'streptozotocin', 'type': 'Chemical', 'start': 122, 'end': 136, 'mesh': 'D013311'}, {'text': 'dementia', 'type': 'Disease', 'start': 188, 'end': 196, 'mesh': 'D003704'}, {'text': ""Alzheimer's disease"", 'type': 'Disease', 'start': 209, 'end': 228, 'mesh': 'D000544'}, {'text': 'glucose', 'type': 'Chemical', 'start': 329, 'end': 336, 'mesh': 'D005947'}, {'text': 'glucose', 'type': 'Chemical', 'start': 351, 'end': 358, 'mesh': 'D005947'}, {'text': 'glucose', 'type': 'Chemical', 'start': 391, 'end': 398, 'mesh': 'D005947'}, {'text': 'd-galactose', 'type': 'Chemical', 'start': 461, 'end': 472, 'mesh': 'D005690'}, {'text': 'd-glucose', 'type': 'Chemical', 'start': 492, 'end': 501, 'mesh': 'D005947'}, {'text': 'glucose', 'type': 'Chemical', 'start': 613, 'end': 620, 'mesh': 'D005947'}, {'text': 'galactose', 'type': 'Chemical', 'start': 688, 'end': 697, 'mesh': 'D005690'}, {'text': 'memory deterioration', 'type': 'Disease', 'start': 705, 'end': 725, 'mesh': 'D008569'}, {'text': 'galactose', 'type': 'Chemical', 'start': 806, 'end': 815, 'mesh': 'D005690'}, {'text': 'galactose', 'type': 'Chemical', 'start': 931, 'end': 940, 'mesh': 'D005690'}, {'text': 'cognitive deficits', 'type': 'Disease', 'start': 970, 'end': 988, 'mesh': 'D003072'}, {'text': 'streptozotocin', 'type': 'Chemical', 'start': 992, 'end': 1006, 'mesh': 'D013311'}, {'text': 'STZ', 'type': 'Chemical', 'start': 1016, 'end': 1019, 'mesh': 'D013311'}, {'text': 'galactose', 'type': 'Chemical', 'start': 1131, 'end': 1140, 'mesh': 'D005690'}, {'text': 'STZ', 'type': 'Chemical', 'start': 1183, 'end': 1186, 'mesh': 'D013311'}, {'text': 'STZ', 'type': 'Chemical', 'start': 1249, 'end': 1252, 'mesh': 'D013311'}, {'text': 'cognitive deficits', 'type': 'Disease', 'start': 1265, 'end': 1283, 'mesh': 'D003072'}, {'text': 'galactose', 'type': 'Chemical', 'start': 1311, 'end': 1320, 'mesh': 'D005690'}, {'text': 'galactose', 'type': 'Chemical', 'start': 1363, 'end': 1372, 'mesh': 'D005690'}, {'text': 'galactose', 'type': 'Chemical', 'start': 1432, 'end': 1441, 'mesh': 'D005690'}, {'text': 'galactose', 'type': 'Chemical', 'start': 1482, 'end': 1491, 'mesh': 'D005690'}, {'text': 'galactose', 'type': 'Chemical', 'start': 1522, 'end': 1531, 'mesh': 'D005690'}, {'text': 'galactose', 'type': 'Chemical', 'start': 1657, 'end': 1666, 'mesh': 'D005690'}, {'text': 'galactose', 'type': 'Chemical', 'start': 1678, 'end': 1687, 'mesh': 'D005690'}, {'text': 'cognitive deficits', 'type': 'Disease', 'start': 1810, 'end': 1828, 'mesh': 'D003072'}, {'text': 'glucose hypometabolism', 'type': 'Disease', 'start': 1845, 'end': 1867, 'mesh': 'D018149'}, {'text': 'AD', 'type': 'Disease', 'start': 1871, 'end': 1873, 'mesh': 'D000544'}]"