diff --git "a/bc5cdr/data/training/CDR_TrainingSet.PubTator.txt" "b/bc5cdr/data/training/CDR_TrainingSet.PubTator.txt"
new file mode 100644--- /dev/null
+++ "b/bc5cdr/data/training/CDR_TrainingSet.PubTator.txt"
@@ -0,0 +1,11923 @@
+227508|t|Naloxone reverses the antihypertensive effect of clonidine.
+227508|a|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.
+227508	0	8	Naloxone	Chemical	D009270
+227508	49	58	clonidine	Chemical	D003000
+227508	93	105	hypertensive	Disease	D006973
+227508	181	190	clonidine	Chemical	D003000
+227508	244	252	nalozone	Chemical	-1
+227508	274	285	hypotensive	Disease	D007022
+227508	306	322	alpha-methyldopa	Chemical	D008750
+227508	354	362	naloxone	Chemical	D009270
+227508	364	372	Naloxone	Chemical	D009270
+227508	469	481	hypertensive	Disease	D006973
+227508	487	496	clonidine	Chemical	D003000
+227508	563	576	[3H]-naloxone	Chemical	-1
+227508	589	597	naloxone	Chemical	D009270
+227508	637	646	clonidine	Chemical	D003000
+227508	671	695	[3H]-dihydroergocryptine	Chemical	-1
+227508	750	762	hypertensive	Disease	D006973
+227508	865	873	naloxone	Chemical	D009270
+227508	878	887	clonidine	Chemical	D003000
+227508	1026	1035	clonidine	Chemical	D003000
+227508	1039	1055	alpha-methyldopa	Chemical	D008750
+227508	CID	D008750	D007022
+
+354896|t|Lidocaine-induced cardiac asystole.
+354896|a|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.
+354896	0	9	Lidocaine	Chemical	D008012
+354896	18	34	cardiac asystole	Disease	D006323
+354896	90	99	lidocaine	Chemical	D008012
+354896	142	152	depression	Disease	D003866
+354896	331	347	bradyarrhythmias	Disease	D001919
+354896	409	418	lidocaine	Chemical	D008012
+354896	CID	D008012	D006323
+
+435349|t|Suxamethonium infusion rate and observed fasciculations. A dose-response study.
+435349|a|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.
+435349	0	13	Suxamethonium	Chemical	D013390
+435349	41	55	fasciculations	Disease	D005207
+435349	80	102	Suxamethonium chloride	Chemical	D013390
+435349	104	107	Sch	Chemical	D013390
+435349	265	272	tetanic	Disease	D013746
+435349	312	315	Sch	Chemical	D013390
+435349	395	409	Fasciculations	Disease	D005207
+435349	483	496	fasciculation	Disease	D005207
+435349	523	536	fasciculation	Disease	D005207
+435349	538	544	twitch	Disease	D013746
+435349	561	568	tetanus	Disease	D013746
+435349	627	641	Fasciculations	Disease	D005207
+435349	673	686	fasciculation	Disease	D005207
+435349	746	759	fasciculation	Disease	D005207
+435349	CID	D013390	D005207
+
+603022|t|Galanthamine hydrobromide, a longer acting anticholinesterase drug, in the treatment of the central effects of scopolamine (Hyoscine).
+603022|a|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.
+603022	0	25	Galanthamine hydrobromide	Chemical	D005702
+603022	111	122	scopolamine	Chemical	D012601
+603022	124	132	Hyoscine	Chemical	D012601
+603022	135	160	Galanthamine hydrobromide	Chemical	D005702
+603022	292	303	scopolamine	Chemical	D012601
+603022	305	313	hyoscine	Chemical	D012601
+603022	315	325	overdosage	Disease	D062787
+603022	352	365	physostigmine	Chemical	D010830
+603022	500	511	scopolamine	Chemical	D012601
+603022	CID	D012601	D062787
+
+1378968|t|Effects of uninephrectomy and high protein feeding on lithium-induced chronic renal failure in rats.
+1378968|a|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)
+1378968	54	61	lithium	Chemical	D008094
+1378968	70	91	chronic renal failure	Disease	D007676
+1378968	111	118	lithium	Chemical	D008094
+1378968	127	138	nephropathy	Disease	D007674
+1378968	309	322	renal failure	Disease	D051437
+1378968	362	369	lithium	Chemical	D008094
+1378968	520	527	lithium	Chemical	D008094
+1378968	581	588	lithium	Chemical	D008094
+1378968	608	615	lithium	Chemical	D008094
+1378968	632	639	lithium	Chemical	D008094
+1378968	820	827	lithium	Chemical	D008094
+1378968	853	860	lithium	Chemical	D008094
+1378968	941	943	Li	Chemical	D008094
+1378968	955	962	Lithium	Chemical	D008094
+1378968	975	986	proteinuria	Disease	D011507
+1378968	1000	1012	hypertension	Disease	D006973
+1378968	1027	1045	glomerulosclerosis	Disease	D005921
+1378968	1087	1100	renal failure	Disease	D051437
+1378968	1156	1166	creatinine	Chemical	D003404
+1378968	1177	1184	lithium	Chemical	D008094
+1378968	1333	1335	Li	Chemical	D008094
+1378968	1379	1381	Li	Chemical	D008094
+1378968	1390	1401	nephropathy	Disease	D007674
+1378968	1466	1477	proteinuria	Disease	D011507
+1378968	1500	1512	hypertension	Disease	D006973
+1378968	1531	1552	chronic renal failure	Disease	D007676
+1378968	CID	D008094	D006973
+1378968	CID	D008094	D011507
+1378968	CID	D008094	D007676
+
+1420741|t|Treatment of Crohn's disease with fusidic acid: an antibiotic with immunosuppressive properties similar to cyclosporin.
+1420741|a|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.
+1420741	13	28	Crohn's disease	Disease	D003424
+1420741	34	46	fusidic acid	Chemical	D005672
+1420741	107	118	cyclosporin	Chemical	D016572
+1420741	217	228	cyclosporin	Chemical	D016572
+1420741	292	307	Crohn's disease	Disease	D003424
+1420741	391	403	fusidic acid	Chemical	D005672
+1420741	467	482	Crohn's disease	Disease	D003424
+1420741	507	519	Fusidic acid	Chemical	D005672
+1420741	743	755	fusidic acid	Chemical	D005672
+1420741	910	916	nausea	Disease	D009325
+1420741	1205	1217	fusidic acid	Chemical	D005672
+1420741	1263	1278	Crohn's disease	Disease	D003424
+1420741	1402	1414	fusidic acid	Chemical	D005672
+1420741	1440	1466	inflammatory bowel disease	Disease	D015212
+1420741	CID	D005672	D009325
+
+1601297|t|Electrocardiographic evidence of myocardial injury in psychiatrically hospitalized cocaine abusers.
+1601297|a|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.
+1601297	33	50	myocardial injury	Disease	D009202
+1601297	83	90	cocaine	Chemical	D003042
+1601297	135	142	cocaine	Chemical	D003042
+1601297	194	207	schizophrenic	Disease	D012559
+1601297	232	239	cocaine	Chemical	D003042
+1601297	305	322	myocardial injury	Disease	D009202
+1601297	334	355	myocardial infarction	Disease	D009203
+1601297	357	365	ischemia	Disease	D007511
+1601297	371	390	bundle branch block	Disease	D002037
+1601297	CID	D003042	D009203
+1601297	CID	D003042	D002037
+
+1967484|t|Sulpiride-induced tardive dystonia.
+1967484|a|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.
+1967484	0	9	Sulpiride	Chemical	D013469
+1967484	18	34	tardive dystonia	Disease	D004421
+1967484	36	45	Sulpiride	Chemical	D013469
+1967484	107	121	antidepressant	Chemical	D000928
+1967484	204	213	sulpiride	Chemical	D013469
+1967484	222	240	tardive dyskinesia	Disease	D004409
+1967484	245	257	parkinsonism	Disease	D010302
+1967484	355	363	dystonia	Disease	D004421
+1967484	395	404	sulpiride	Chemical	D013469
+1967484	456	465	sulpiride	Chemical	D013469
+1967484	474	490	tardive dystonia	Disease	D004421
+1967484	CID	D013469	D004421
+
+2234245|t|Ocular and auditory toxicity in hemodialyzed patients receiving desferrioxamine.
+2234245|a|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.
+2234245	0	28	Ocular and auditory toxicity	Disease	D014786|D006311	Ocular toxicity|auditory toxicity
+2234245	64	79	desferrioxamine	Chemical	D003676
+2234245	151	166	desferrioxamine	Chemical	D003676
+2234245	250	270	audiovisual toxicity	Disease	D014786|D006311
+2234245	314	341	visual or auditory toxicity	Disease	D014786|D006311	visual toxicity|auditory toxicity
+2234245	457	472	Visual toxicity	Disease	D014786
+2234245	534	548	dyschromatopsy	Disease	-1
+2234245	576	599	a loss of visual acuity	Disease	D014786
+2234245	604	631	pigmentary retinal deposits	Disease	D012164
+2234245	633	650	Auditory toxicity	Disease	D006311
+2234245	697	724	neurosensorial hearing loss	Disease	D006319
+2234245	766	781	Desferrioxamine	Chemical	D003676
+2234245	911	923	hearing loss	Disease	D034381
+2234245	970	978	toxicity	Disease	D064420
+2234245	1030	1045	desferrioxamine	Chemical	D003676
+2234245	1097	1106	aluminium	Chemical	-1
+2234245	1144	1164	audiovisual toxicity	Disease	D014786|D006311
+2234245	1234	1249	desferrioxamine	Chemical	D003676
+2234245	CID	D003676	D012164
+2234245	CID	D003676	D014786
+2234245	CID	D003676	D006319
+
+2385256|t|Myasthenia gravis presenting as weakness after magnesium administration.
+2385256|a|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.
+2385256	0	17	Myasthenia gravis	Disease	D009157
+2385256	47	56	magnesium	Chemical	D008274
+2385256	119	140	neuromuscular disease	Disease	D009468
+2385256	162	174	quadriplegic	Disease	D011782
+2385256	192	201	magnesium	Chemical	D008274
+2385256	221	233	preeclampsia	Disease	D011225
+2385256	245	254	magnesium	Chemical	D008274
+2385256	321	330	magnesium	Chemical	D008274
+2385256	525	560	postsynaptic neuromuscular blockade	Disease	D009468
+2385256	691	704	acetylcholine	Chemical	D000109
+2385256	761	770	paralysis	Disease	D010243
+2385256	777	786	magnesium	Chemical	D008274
+2385256	844	861	myasthenia gravis	Disease	D009157
+2385256	1024	1033	magnesium	Chemical	D008274
+2385256	1078	1116	disorder of neuromuscular transmission	Disease	D020511
+2385256	CID	D008274	D009157
+
+2505783|t|Chloroacetaldehyde and its contribution to urotoxicity during treatment with cyclophosphamide or ifosfamide. An experimental study/short communication.
+2505783|a|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.
+2505783	0	18	Chloroacetaldehyde	Chemical	C004656
+2505783	77	93	cyclophosphamide	Chemical	D003520
+2505783	97	107	ifosfamide	Chemical	D007069
+2505783	192	210	chloroacetaldehyde	Chemical	C004656
+2505783	212	215	CAA	Chemical	C004656
+2505783	349	352	CAA	Chemical	C004656
+2505783	375	395	hemorrhagic cystitis	Disease	D006470|D003556	hemorrhagic|cystitis
+2505783	423	426	CAA	Chemical	C004656
+2505783	476	490	bladder damage	Disease	D001745
+2505783	534	537	CAA	Chemical	C004656
+2505783	614	619	mesna	Chemical	D015080
+2505783	CID	C004656	D003556
+2505783	CID	C004656	D006470
+
+2515254|t|Source of pain and primitive dysfunction in migraine: an identical site?
+2515254|a|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.
+2515254	10	14	pain	Disease	D010146
+2515254	44	52	migraine	Disease	D008881
+2515254	87	95	migraine	Disease	D008881
+2515254	156	169	nitroglycerin	Chemical	D005996
+2515254	255	263	migraine	Disease	D008881
+2515254	288	301	nitroglycerin	Chemical	D005996
+2515254	386	394	migraine	Disease	D008881
+2515254	461	474	nitroglycerin	Chemical	D005996
+2515254	557	565	migraine	Disease	D008881
+2515254	589	597	migraine	Disease	D008881
+2515254	617	630	nitroglycerin	Chemical	D005996
+2515254	693	697	pain	Disease	D010146
+2515254	790	798	migraine	Disease	D008881
+2515254	851	859	migraine	Disease	D008881
+2515254	CID	D005996	D008881
+
+2572625|t|Clotiazepam-induced acute hepatitis.
+2572625|a|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.
+2572625	0	11	Clotiazepam	Chemical	C084599
+2572625	26	35	hepatitis	Disease	D056486
+2572625	89	98	hepatitis	Disease	D056486
+2572625	104	137	extensive hepatocellular necrosis	Disease	D047508
+2572625	185	196	clotiazepam	Chemical	C084599
+2572625	200	215	thienodiazepine	Chemical	C013295
+2572625	228	239	Clotiazepam	Chemical	C084599
+2572625	314	329	benzodiazepines	Chemical	D001569
+2572625	353	364	clotiazepam	Chemical	C084599
+2572625	432	441	hepatitis	Disease	D056486
+2572625	471	482	clotiazepam	Chemical	C084599
+2572625	500	509	hepatitis	Disease	D056486
+2572625	546	560	hepatotoxicity	Disease	D056486
+2572625	569	580	clotiazepam	Chemical	C084599
+2572625	593	608	benzodiazepines	Chemical	D001569
+2572625	CID	C084599	D056486
+
+2632720|t|Arterial hypertension as a complication of prolonged ketoconazole treatment.
+2632720|a|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.
+2632720	9	21	hypertension	Disease	D006973
+2632720	53	65	ketoconazole	Chemical	D007654
+2632720	101	119	Cushing's syndrome	Disease	D003480
+2632720	154	166	ketoconazole	Chemical	D007654
+2632720	187	199	hypertension	Disease	D006973
+2632720	246	254	cortisol	Chemical	D006854
+2632720	290	302	ketoconazole	Chemical	D007654
+2632720	366	378	hypertension	Disease	D006973
+2632720	467	486	deoxycorticosterone	Chemical	D003900
+2632720	491	507	11-deoxycortisol	Chemical	D003350
+2632720	572	591	deoxycorticosterone	Chemical	D003900
+2632720	596	612	11-deoxycortisol	Chemical	D003350
+2632720	628	639	aldosterone	Chemical	D000450
+2632720	770	782	ketoconazole	Chemical	D007654
+2632720	847	859	hypertension	Disease	D006973
+2632720	CID	D007654	D006973
+
+2670794|t|Effects of an inhibitor of angiotensin converting enzyme (Captopril) on pulmonary and renal insufficiency due to intravascular coagulation in the rat.
+2670794|a|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.
+2670794	27	38	angiotensin	Chemical	D000809
+2670794	58	67	Captopril	Chemical	D002216
+2670794	72	105	pulmonary and renal insufficiency	Disease	D011665|D051437	pulmonary insufficiency|renal insufficiency
+2670794	113	138	intravascular coagulation	Disease	D004211
+2670794	164	189	intravascular coagulation	Disease	D004211
+2670794	250	265	tranexamic acid	Chemical	D014148
+2670794	267	271	AMCA	Chemical	D014148
+2670794	298	331	pulmonary and renal insufficiency	Disease	D011665|D051437	pulmonary insufficiency|renal insufficiency
+2670794	364	370	trauma	Disease	D014947
+2670794	374	380	sepsis	Disease	D018805
+2670794	402	411	Captopril	Chemical	D002216
+2670794	439	450	angiotensin	Chemical	D000809
+2670794	489	522	pulmonary and renal insufficiency	Disease	D011665|D051437	pulmonary insufficiency|renal insufficiency
+2670794	705	714	Captopril	Chemical	D002216
+2670794	763	775	Renal damage	Disease	D007674
+2670794	813	817	urea	Chemical	D014508
+2670794	856	865	Captopril	Chemical	D002216
+2670794	975	979	AMCA	Chemical	D014148
+2670794	1023	1032	Captopril	Chemical	D002216
+2670794	1138	1153	Angiotension II	Chemical	D000804
+2670794	1173	1185	prostacyclin	Chemical	D011464
+2670794	1215	1225	bradykinin	Chemical	D001920
+2670794	1228	1237	Captopril	Chemical	D002216
+2670794	1504	1517	kidney damage	Disease	D007674
+2670794	CID	D014148	D004211
+
+2696505|t|A randomized comparison of labetalol and nitroprusside for induced hypotension.
+2696505|a|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.
+2696505	27	36	labetalol	Chemical	D007741
+2696505	41	54	nitroprusside	Chemical	D009599
+2696505	67	78	hypotension	Disease	D007022
+2696505	103	112	labetalol	Chemical	D007741
+2696505	121	132	hypotension	Disease	D007022
+2696505	137	150	nitroprusside	Chemical	D009599
+2696505	159	170	hypotension	Disease	D007022
+2696505	350	392	reductions in mean arterial blood pressure	Disease	D007022
+2696505	491	532	increase in heart rate and cardiac output	Disease	D016534
+2696505	542	554	hypertension	Disease	D006973
+2696505	611	624	nitroprusside	Chemical	D009599
+2696505	626	635	Labetalol	Chemical	D007741
+2696505	707	710	PO2	Chemical	C093415
+2696505	759	768	labetalol	Chemical	D007741
+2696505	792	805	nitroprusside	Chemical	D009599
+2696505	CID	D009599	D007022
+2696505	CID	D009599	D016534
+2696505	CID	D007741	D007022
+
+2924746|t|Chronic carbamazepine treatment in the rat: efficacy, toxicity, and effect on plasma and tissue folate concentrations.
+2924746|a|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.
+2924746	8	21	carbamazepine	Chemical	D002220
+2924746	54	62	toxicity	Disease	D064420
+2924746	96	102	folate	Chemical	D005492
+2924746	119	125	Folate	Chemical	D005492
+2924746	206	219	Carbamazepine	Chemical	D002220
+2924746	221	224	CBZ	Chemical	D002220
+2924746	354	357	CBZ	Chemical	D002220
+2924746	371	377	folate	Chemical	D005492
+2924746	463	479	propylene glycol	Chemical	D019946
+2924746	565	573	seizures	Disease	D012640
+2924746	588	599	weight gain	Disease	D015430
+2924746	601	609	Seizures	Disease	D012640
+2924746	621	644	hexafluorodiethyl ether	Chemical	D005481
+2924746	646	650	HFDE	Chemical	D005481
+2924746	716	719	CBZ	Chemical	D002220
+2924746	725	733	seizures	Disease	D012640
+2924746	796	799	CBZ	Chemical	D002220
+2924746	894	898	HFDE	Chemical	D005481
+2924746	907	915	seizures	Disease	D012640
+2924746	955	966	weight gain	Disease	D015430
+2924746	998	1001	CBZ	Chemical	D002220
+2924746	1134	1137	CBZ	Chemical	D002220
+2924746	1172	1178	folate	Chemical	D005492
+2924746	1223	1229	folate	Chemical	D005492
+2924746	CID	D005481	D012640
+
+2951327|t|Inhibition of sympathoadrenal activity by atrial natriuretic factor in dogs.
+2951327|a|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)
+2951327	132	138	sodium	Chemical	D012964
+2951327	225	239	norepinephrine	Chemical	D009638
+2951327	244	255	epinephrine	Chemical	D004837
+2951327	588	599	tachycardia	Disease	D013610
+2951327	627	641	norepinephrine	Chemical	D009638
+2951327	734	745	hypotension	Disease	D007022
+2951327	757	768	hydralazine	Chemical	D006830
+2951327	772	785	nitroglycerin	Chemical	D005996
+2951327	807	818	epinephrine	Chemical	D004837
+2951327	CID	D005996	D007022
+2951327	CID	D006830	D007022
+
+3192036|t|Death from chemotherapy in gestational trophoblastic disease.
+3192036|a|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)
+3192036	0	5	Death	Disease	D003643
+3192036	27	60	gestational trophoblastic disease	Disease	D031901
+3192036	175	190	choriocarcinoma	Disease	D002822
+3192036	399	408	Etoposide	Chemical	D005047
+3192036	417	429	Methotrexate	Chemical	D008727
+3192036	431	447	Cyclophosphamide	Chemical	D003520
+3192036	449	460	Actomycin-D	Chemical	D003609
+3192036	466	475	Cisplatin	Chemical	D002945
+3192036	534	546	Methotrexate	Chemical	D008727
+3192036	548	557	Etoposide	Chemical	D005047
+3192036	562	578	Cyclophosphamide	Chemical	D003520
+3192036	701	722	pulmonary obstruction	Disease	D011655
+3192036	854	859	tumor	Disease	D009369
+3192036	860	868	necrosis	Disease	D009336
+3192036	961	966	tumor	Disease	D009369
+3192036	1009	1014	tumor	Disease	D009369
+3192036	1107	1112	tumor	Disease	D009369
+3192036	1224	1232	embolism	Disease	D004617
+3192036	1273	1281	necrosis	Disease	D009336
+3192036	1335	1347	pelvic tumor	Disease	D010386
+3192036	CID	D005047	D011655
+3192036	CID	D008727	D011655
+3192036	CID	D003520	D011655
+
+3409645|t|Sexual dysfunction among patients with arthritis.
+3409645|a|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.
+3409645	0	18	Sexual dysfunction	Disease	D012735
+3409645	39	48	arthritis	Disease	D001168
+3409645	70	79	arthritis	Disease	D001168
+3409645	84	102	sexual dysfunction	Disease	D012735
+3409645	144	164	rheumatoid arthritis	Disease	D001172
+3409645	166	180	osteoarthritis	Disease	D010003
+3409645	185	204	spondyloarthropathy	Disease	D025242
+3409645	286	300	depressed mood	Disease	D003866
+3409645	378	397	Sexual dysfunctions	Disease	D012735
+3409645	515	524	Impotence	Disease	D007172
+3409645	642	654	methotrexate	Chemical	D008727
+3409645	656	670	Depressed mood	Disease	D003866
+3409645	768	777	impotence	Disease	D007172
+3409645	853	862	arthritis	Disease	D001168
+3409645	887	905	sexual dysfunction	Disease	D012735
+3409645	CID	D008727	D007172
+
+3412544|t|Does paracetamol cause urothelial cancer or renal papillary necrosis?
+3412544|a|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.
+3412544	5	16	paracetamol	Chemical	D000082
+3412544	23	40	urothelial cancer	Disease	D014523
+3412544	44	68	renal papillary necrosis	Disease	D007681
+3412544	93	117	renal papillary necrosis	Disease	D007681
+3412544	121	166	cancer of the renal pelvis, ureter or bladder	Disease	D007680|D014516|D001749	cancer of the renal pelvis|cancer of the ureter|cancer of the bladder
+3412544	205	215	phenacetin	Chemical	D010615
+3412544	219	230	paracetamol	Chemical	D000082
+3412544	327	351	renal papillary necrosis	Disease	D007681
+3412544	399	409	phenacetin	Chemical	D010615
+3412544	445	483	cancer of the renal pelvis and bladder	Disease	D007680|D001749	cancer of the renal pelvis|cancer of the bladder
+3412544	496	511	ureteric cancer	Disease	D014516
+3412544	580	591	paracetamol	Chemical	D000082
+3412544	608	632	renal papillary necrosis	Disease	D007681
+3412544	649	656	cancers	Disease	D009369
+3412544	712	732	cancer of the ureter	Disease	D014516
+3412544	CID	D010615	D007681
+3412544	CID	D010615	D001749
+3412544	CID	D010615	D007680
+
+3425586|t|Dapsone-associated Heinz body hemolytic anemia in a Cambodian woman with hemoglobin E trait.
+3425586|a|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.
+3425586	0	7	Dapsone	Chemical	D003622
+3425586	30	46	hemolytic anemia	Disease	D000743
+3425586	144	151	leprosy	Disease	D007918
+3425586	175	191	hemolytic anemia	Disease	D000743
+3425586	215	222	dapsone	Chemical	D003622
+3425586	272	281	hemolysis	Disease	D006461
+3425586	374	385	glutathione	Chemical	D005978
+3425586	387	390	GSH	Chemical	D005978
+3425586	407	410	GSH	Chemical	D005978
+3425586	426	443	pentose phosphate	Chemical	D010428
+3425586	466	473	dapsone	Chemical	D003622
+3425586	580	587	dapsone	Chemical	D003622
+3425586	638	641	GSH	Chemical	D005978
+3425586	654	657	GSH	Chemical	D005978
+3425586	685	702	pentose phosphate	Chemical	D010428
+3425586	729	736	dapsone	Chemical	D003622
+3425586	897	904	dapsone	Chemical	D003622
+3425586	920	936	hemolytic anemia	Disease	D000743
+3425586	1116	1125	infection	Disease	D007239
+3425586	CID	D003622	D000743
+
+3437726|t|Severe complications of antianginal drug therapy in a patient identified as a poor metabolizer of metoprolol, propafenone, diltiazem, and sparteine.
+3437726|a|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.
+3437726	98	108	metoprolol	Chemical	D008790
+3437726	110	121	propafenone	Chemical	D011405
+3437726	123	132	diltiazem	Chemical	D004110
+3437726	138	147	sparteine	Chemical	D013034
+3437726	186	209	coronary artery disease	Disease	D003324
+3437726	237	242	shock	Disease	D012769
+3437726	253	261	AV block	Disease	D054537
+3437726	270	281	hypotension	Disease	D007022
+3437726	287	321	impairment of ventricular function	Disease	D018754
+3437726	384	394	metoprolol	Chemical	D008790
+3437726	480	489	diltiazem	Chemical	D004110
+3437726	609	619	metoprolol	Chemical	D008790
+3437726	650	659	diltiazem	Chemical	D004110
+3437726	822	832	metoprolol	Chemical	D008790
+3437726	834	843	diltiazem	Chemical	D004110
+3437726	845	856	propafenone	Chemical	D011405
+3437726	908	917	sparteine	Chemical	D013034
+3437726	938	950	debrisoquine	Chemical	D003647
+3437726	951	960	sparteine	Chemical	D013034
+3437726	1208	1217	sparteine	Chemical	D013034
+3437726	1218	1230	debrisoquine	Chemical	D003647
+3437726	1328	1350	adverse drug reactions	Disease	D064420
+3437726	CID	D004110	D007022
+3437726	CID	D004110	D018754
+3437726	CID	D008790	D018754
+3437726	CID	D008790	D007022
+3437726	CID	D004110	D054537
+3437726	CID	D008790	D054537
+
+3693336|t|Triazolam-induced brief episodes of secondary mania in a depressed patient.
+3693336|a|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.
+3693336	0	9	Triazolam	Chemical	D014229
+3693336	46	51	mania	Disease	D001714
+3693336	57	66	depressed	Disease	D003866
+3693336	91	100	triazolam	Chemical	D014229
+3693336	138	143	mania	Disease	D001714
+3693336	149	158	depressed	Disease	D003866
+3693336	186	209	organic mental disorder	Disease	D019965
+3693336	211	219	delirium	Disease	D003693
+3693336	239	244	Manic	Disease	D001714
+3693336	302	311	triazolam	Chemical	D014229
+3693336	346	354	triazolo	Chemical	D014229
+3693336	CID	D014229	D001714
+
+3780846|t|On the mechanisms of the development of tolerance to the muscular rigidity produced by morphine in rats.
+3780846|a|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.
+3780846	57	74	muscular rigidity	Disease	D009127
+3780846	87	95	morphine	Chemical	D009020
+3780846	141	158	muscular rigidity	Disease	D009127
+3780846	171	179	morphine	Chemical	D009020
+3780846	249	257	morphine	Chemical	D009020
+3780846	294	302	rigidity	Disease	D009127
+3780846	383	391	morphine	Chemical	D009020
+3780846	505	513	rigidity	Disease	D009127
+3780846	537	545	morphine	Chemical	D009020
+3780846	608	616	akinetic	Disease	D018476
+3780846	675	683	rigidity	Disease	D009127
+3780846	760	768	akinetic	Disease	D018476
+3780846	772	784	hyperkinetic	Disease	D006948
+3780846	863	871	rigidity	Disease	D009127
+3780846	976	987	haloperidol	Chemical	D006220
+3780846	1116	1124	rigidity	Disease	D009127
+3780846	1164	1175	Haloperidol	Chemical	D006220
+3780846	1189	1197	rigidity	Disease	D009127
+3780846	1326	1334	rigidity	Disease	D009127
+3780846	1379	1387	morphine	Chemical	D009020
+3780846	1584	1592	rigidity	Disease	D009127
+3780846	CID	D006220	D009127
+3780846	CID	D009020	D009127
+3780846	CID	D009020	D006948
+3780846	CID	D009020	D018476
+
+3800626|t|Compression neuropathy of the radial nerve due to pentazocine-induced fibrous myopathy.
+3800626|a|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.
+3800626	0	42	Compression neuropathy of the radial nerve	Disease	D009408|D020425	Compression neuropathy|neuropathy of the radial nerve
+3800626	50	61	pentazocine	Chemical	D010423
+3800626	70	86	fibrous myopathy	Disease	D005355|D009135
+3800626	88	104	Fibrous myopathy	Disease	D005355|D009135
+3800626	153	164	pentazocine	Chemical	D010423
+3800626	185	207	compression neuropathy	Disease	D009408
+3800626	243	254	pentazocine	Chemical	D010423
+3800626	263	271	myopathy	Disease	D009135
+3800626	345	356	pentazocine	Chemical	D010423
+3800626	365	381	fibrous myopathy	Disease	D005355|D009135
+3800626	620	636	fibrous myopathy	Disease	D005355|D009135
+3800626	CID	D010423	D005355
+3800626	CID	D010423	D009135
+3800626	CID	D010423	D020425
+3800626	CID	D010423	D009408
+
+3827439|t|Recurrent reversible acute renal failure from amphotericin.
+3827439|a|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.
+3827439	21	40	acute renal failure	Disease	D058186
+3827439	46	58	amphotericin	Chemical	D000666
+3827439	87	96	cirrhosis	Disease	D005355
+3827439	114	128	sporotrichosis	Disease	D013174
+3827439	139	158	acute renal failure	Disease	D058186
+3827439	203	217	amphotericin B	Chemical	D000666
+3827439	268	281	renal failure	Disease	D051437
+3827439	370	387	renal dysfunction	Disease	D007674
+3827439	405	417	amphotericin	Chemical	D000666
+3827439	536	555	acute renal failure	Disease	D058186
+3827439	CID	D000666	D058186
+
+3997294|t|Pneumonitis with pleural and pericardial effusion and neuropathy during amiodarone therapy.
+3997294|a|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.
+3997294	17	49	pleural and pericardial effusion	Disease	D010996|D010490	pleural effusion|pericardial effusion
+3997294	54	64	neuropathy	Disease	D009422
+3997294	72	82	amiodarone	Chemical	D000638
+3997294	107	125	sinuatrial disease	Disease	D002318
+3997294	167	177	amiodarone	Chemical	D000638
+3997294	262	295	supraventricular tachyarrhythmias	Disease	D013617
+3997294	310	321	pneumonitis	Disease	D011014
+3997294	323	356	pleural and pericardial effusions	Disease	D010996|D010490	pleural effusions|pericardial effusions
+3997294	378	403	proximal motor neuropathy	Disease	D009468
+3997294	462	472	amiodarone	Chemical	D000638
+3997294	492	504	prednisolone	Chemical	D011239
+3997294	593	603	amiodarone	Chemical	D000638
+3997294	604	615	pneumonitis	Disease	D011014
+3997294	641	651	amiodarone	Chemical	D000638
+3997294	678	685	steroid	Chemical	D013256
+3997294	CID	D000638	D010490
+3997294	CID	D000638	D009468
+3997294	CID	D000638	D010996
+3997294	CID	D000638	D011014
+
+4071154|t|Indomethacin-induced renal insufficiency: recurrence on rechallenge.
+4071154|a|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.
+4071154	0	12	Indomethacin	Chemical	D007213
+4071154	21	40	renal insufficiency	Disease	D051437
+4071154	111	124	renal failure	Disease	D051437
+4071154	130	142	hyperkalemia	Disease	D006947
+4071154	161	170	cirrhosis	Disease	D005355
+4071154	172	179	ascites	Disease	D001201
+4071154	185	198	cor pulmonale	Disease	D011660
+4071154	205	217	indomethacin	Chemical	D007213
+4071154	328	340	indomethacin	Chemical	D007213
+4071154	379	387	oliguria	Disease	D009846
+4071154	444	458	prostaglandins	Chemical	D011453
+4071154	657	676	acute renal failure	Disease	D058186
+4071154	CID	D007213	D006947
+4071154	CID	D007213	D009846
+4071154	CID	D007213	D058186
+4071154	CID	D007213	D005355
+4071154	CID	D007213	D001201
+4071154	CID	D007213	D011660
+
+6103707|t|Comparison of the subjective effects and plasma concentrations following oral and i.m. administration of flunitrazepam in volunteers.
+6103707|a|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.
+6103707	105	118	flunitrazepam	Chemical	D005445
+6103707	134	147	Flunitrazepam	Chemical	D005445
+6103707	638	647	Dizziness	Disease	D004244
+6103707	718	722	pain	Disease	D010146
+6103707	744	757	flunitrazepam	Chemical	D005445
+6103707	CID	D005445	D004244
+6103707	CID	D005445	D010146
+
+6229975|t|Changes in heart size during long-term timolol treatment after myocardial infarction.
+6229975|a|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.
+6229975	39	46	timolol	Chemical	D013999
+6229975	63	84	myocardial infarction	Disease	D009203
+6229975	110	117	timolol	Chemical	D013999
+6229975	148	169	myocardial infarction	Disease	D009203
+6229975	254	261	timolol	Chemical	D013999
+6229975	308	315	timolol	Chemical	D013999
+6229975	484	491	timolol	Chemical	D013999
+6229975	500	511	bradycardia	Disease	D001919
+6229975	569	576	timolol	Chemical	D013999
+6229975	694	706	cardiomegaly	Disease	D006332
+6229975	772	782	infarction	Disease	D007238
+6229975	856	863	timolol	Chemical	D013999
+6229975	CID	D013999	D006332
+
+6286738|t|Vitamin D3 toxicity in dairy cows.
+6286738|a|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.
+6286738	0	10	Vitamin D3	Chemical	D002762
+6286738	11	19	toxicity	Disease	D064420
+6286738	61	71	vitamin D3	Chemical	D002762
+6286738	95	105	vitamin D3	Chemical	D002762
+6286738	138	151	hypercalcemia	Disease	D006934
+6286738	153	170	hyperphosphatemia	Disease	D054559
+6286738	195	205	vitamin D3	Chemical	D002762
+6286738	300	307	Calcium	Chemical	D002118
+6286738	373	383	vitamin D3	Chemical	D002762
+6286738	492	502	vitamin D3	Chemical	D002762
+6286738	519	529	milk fever	Disease	D010319
+6286738	621	631	milk fever	Disease	D010319
+6286738	661	671	vitamin D3	Chemical	D002762
+6286738	672	680	toxicity	Disease	D064420
+6286738	791	801	vitamin D3	Chemical	D002762
+6286738	802	810	toxicity	Disease	D064420
+6286738	927	935	toxicity	Disease	D064420
+6286738	939	949	vitamin D3	Chemical	D002762
+6286738	1020	1030	vitamin D3	Chemical	D002762
+6286738	1044	1054	milk fever	Disease	D010319
+6286738	1077	1087	milk fever	Disease	D010319
+6286738	1107	1117	vitamin D3	Chemical	D002762
+6286738	1156	1166	milk fever	Disease	D010319
+6286738	CID	D002762	D006934
+6286738	CID	D002762	D054559
+
+6287825|t|Diseases of peripheral nerves as seen in the Nigerian African.
+6287825|a|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.
+6287825	0	29	Diseases of peripheral nerves	Disease	D010523
+6287825	108	132	peripheral nerve disease	Disease	D010523
+6287825	305	329	Sensori-motor neuropathy	Disease	D010523
+6287825	368	392	Guillain-Barr   syndrome	Disease	D020275
+6287825	477	493	motor neuropathy	Disease	D010523
+6287825	495	516	Peripheral neuropathy	Disease	D010523
+6287825	524	546	nutritional deficiency	Disease	D044342
+6287825	550	558	thiamine	Chemical	D013831
+6287825	563	573	riboflavin	Chemical	D012256
+6287825	629	653	sensori-motor neuropathy	Disease	D010523
+6287825	655	672	Diabetes mellitus	Disease	D003920
+6287825	696	716	autonomic neuropathy	Disease	D009422
+6287825	718	727	Isoniazid	Chemical	D007538
+6287825	772	782	neuropathy	Disease	D009422
+6287825	784	792	Migraine	Disease	D008881
+6287825	828	846	cranial neuropathy	Disease	D003389
+6287825	856	868	malignancies	Disease	D009369
+6287825	1030	1040	neuropathy	Disease	D009422
+6287825	1078	1105	connective tissue disorders	Disease	D003240
+6287825	1198	1210	neuropathies	Disease	D009422
+6287825	CID	D012256	D010523
+6287825	CID	D013831	D010523
+6287825	CID	D007538	D010523
+
+6386793|t|A double-blind study of the efficacy and safety of dothiepin hydrochloride in the treatment of major depressive disorder.
+6386793|a|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.
+6386793	51	74	dothiepin hydrochloride	Chemical	D004308
+6386793	101	120	depressive disorder	Disease	D003866
+6386793	173	182	dothiepin	Chemical	D004308
+6386793	187	200	amitriptyline	Chemical	D000639
+6386793	249	258	depressed	Disease	D003866
+6386793	272	281	Dothiepin	Chemical	D004308
+6386793	286	299	amitriptyline	Chemical	D000639
+6386793	354	372	depressive illness	Disease	D003866
+6386793	495	509	blurred vision	Disease	D014786
+6386793	511	520	dry mouth	Disease	D014987
+6386793	566	575	dothiepin	Chemical	D004308
+6386793	586	599	amitriptyline	Chemical	D000639
+6386793	601	610	Dothiepin	Chemical	D004308
+6386793	732	741	Dothiepin	Chemical	D004308
+6386793	776	790	antidepressant	Chemical	D000928
+6386793	836	849	amitriptyline	Chemical	D000639
+6386793	870	879	depressed	Disease	D003866
+6386793	CID	D000639	D014786
+6386793	CID	D000639	D014987
+
+6387529|t|Behavioral effects of diazepam and propranolol in patients with panic disorder and agoraphobia.
+6387529|a|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.
+6387529	22	30	diazepam	Chemical	D003975
+6387529	35	46	propranolol	Chemical	D011433
+6387529	64	78	panic disorder	Disease	D016584
+6387529	83	94	agoraphobia	Disease	D000379
+6387529	125	133	diazepam	Chemical	D003975
+6387529	204	215	propranolol	Chemical	D011433
+6387529	329	344	panic disorders	Disease	D016584
+6387529	349	360	agoraphobia	Disease	D000379
+6387529	442	472	impaired immediate free recall	Disease	D008569
+6387529	506	514	diazepam	Chemical	D003975
+6387529	520	531	propranolol	Chemical	D011433
+6387529	533	570	Delayed free recall was also impaired	Disease	D008569
+6387529	634	645	propranolol	Chemical	D011433
+6387529	651	659	diazepam	Chemical	D003975
+6387529	693	701	diazepam	Chemical	D003975
+6387529	707	718	propranolol	Chemical	D011433
+6387529	973	994	behavioral impairment	Disease	D001523
+6387529	CID	D011433	D008569
+6387529	CID	D003975	D008569
+
+6692345|t|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.
+6692345|a|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.
+6692345	10	17	aspirin	Chemical	D001241
+6692345	21	66	N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide	Chemical	D005200
+6692345	176	183	aspirin	Chemical	D001241
+6692345	189	234	N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide	Chemical	D005200
+6692345	236	241	FANFT	Chemical	D005200
+6692345	286	291	FANFT	Chemical	D005200
+6692345	300	318	bladder carcinomas	Disease	D001749
+6692345	350	368	forestomach tumors	Disease	D013274
+6692345	449	454	FANFT	Chemical	D005200
+6692345	481	488	aspirin	Chemical	D001241
+6692345	534	541	aspirin	Chemical	D001241
+6692345	589	594	FANFT	Chemical	D005200
+6692345	627	632	FANFT	Chemical	D005200
+6692345	707	714	aspirin	Chemical	D001241
+6692345	814	821	aspirin	Chemical	D001241
+6692345	841	846	FANFT	Chemical	D005200
+6692345	1007	1012	FANFT	Chemical	D005200
+6692345	1013	1027	carcinogenesis	Disease	D063646
+6692345	1069	1076	aspirin	Chemical	D001241
+6692345	1089	1094	FANFT	Chemical	D005200
+6692345	1273	1280	aspirin	Chemical	D001241
+6692345	CID	D005200	D001749
+6692345	CID	D005200	D013274
+
+6773726|t|Provocation of postural hypotension by nitroglycerin in diabetic autonomic neuropathy?
+6773726|a|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.
+6773726	24	35	hypotension	Disease	D007022
+6773726	39	52	nitroglycerin	Chemical	D005996
+6773726	56	85	diabetic autonomic neuropathy	Disease	D003929
+6773726	101	114	nitroglycerin	Chemical	D005996
+6773726	195	203	diabetic	Disease	D003920
+6773726	221	241	autonomic neuropathy	Disease	D009422
+6773726	249	257	diabetic	Disease	D003920
+6773726	272	292	autonomic neuropathy	Disease	D009422
+6773726	404	417	nitroglycerin	Chemical	D005996
+6773726	449	457	diabetic	Disease	D003920
+6773726	475	495	autonomic neuropathy	Disease	D009422
+6773726	603	611	diabetic	Disease	D003920
+6773726	626	646	autonomic neuropathy	Disease	D009422
+6773726	745	753	diabetic	Disease	D003920
+6773726	788	808	autonomic neuropathy	Disease	D009422
+6773726	CID	D005996	D007022
+
+6888657|t|Characterization of estrogen-induced adenohypophyseal tumors in the Fischer 344 rat.
+6888657|a|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.
+6888657	20	28	estrogen	Chemical	D004967
+6888657	37	60	adenohypophyseal tumors	Disease	D010911
+6888657	85	101	Pituitary tumors	Disease	D010911
+6888657	161	179	diethylstilbestrol	Chemical	D004054
+6888657	181	184	DES	Chemical	D004054
+6888657	272	275	DES	Chemical	D004054
+6888657	308	311	DES	Chemical	D004054
+6888657	761	772	acriflavine	Chemical	D000167
+6888657	835	838	DES	Chemical	D004054
+6888657	1141	1144	DES	Chemical	D004054
+6888657	1172	1175	DES	Chemical	D004054
+6888657	1452	1455	DES	Chemical	D004054
+6888657	1596	1599	DES	Chemical	D004054
+6888657	1608	1613	tumor	Disease	D009369
+6888657	CID	D004054	D010911
+
+7265370|t|Triamterene nephrolithiasis complicating dyazide therapy.
+7265370|a|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.
+7265370	0	11	Triamterene	Chemical	D014223
+7265370	12	27	nephrolithiasis	Disease	D053040
+7265370	41	48	dyazide	Chemical	C020743
+7265370	68	79	triamterene	Chemical	D014223
+7265370	80	95	nephrolithiasis	Disease	D053040
+7265370	134	165	hydrochlorothiazide-triamterene	Chemical	C020743
+7265370	178	190	hypertension	Disease	D006973
+7265370	250	261	triamterene	Chemical	D014223
+7265370	286	301	uric acid salts	Chemical	D014527|D012492
+7265370	321	332	triamterene	Chemical	D014223
+7265370	333	348	nephrolithiasis	Disease	D053040
+7265370	CID	D014223	D053040
+
+7423039|t|Metabolic involvement in adriamycin cardiotoxicity.
+7423039|a|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.
+7423039	25	35	adriamycin	Chemical	D004317
+7423039	36	50	cardiotoxicity	Disease	D066126
+7423039	56	67	cardiotoxic	Disease	D066126
+7423039	79	89	adriamycin	Chemical	D004317
+7423039	163	173	Adriamycin	Chemical	D004317
+7423039	393	411	phosphorylcreatine	Chemical	D010725
+7423039	449	459	adriamycin	Chemical	D004317
+7423039	554	571	phophorylcreatine	Chemical	D010725
+7423039	642	650	creatine	Chemical	D003401
+7423039	687	696	adenosine	Chemical	D000241
+7423039	752	755	ATP	Chemical	D000255
+7423039	830	833	ATP	Chemical	D000255
+7423039	847	857	adriamycin	Chemical	D004317
+7423039	889	898	adenosine	Chemical	D000241
+7423039	CID	D004317	D066126
+
+7444978|t|Age-dependent sensitivity of the rat to neurotoxic effects of streptomycin.
+7444978|a|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.
+7444978	40	50	neurotoxic	Disease	D020258
+7444978	62	74	streptomycin	Chemical	D013307
+7444978	76	88	Streptomycin	Chemical	D013307
+7444978	313	331	Abnormal movements	Disease	D004409
+7444978	336	344	deafness	Disease	D003638
+7444978	588	600	streptomycin	Chemical	D013307
+7444978	659	670	dyskinesias	Disease	D004409
+7444978	CID	D013307	D004409
+7444978	CID	D013307	D003638
+
+7834920|t|Crescentic fibrillary glomerulonephritis associated with intermittent rifampin therapy for pulmonary tuberculosis.
+7834920|a|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.
+7834920	22	40	glomerulonephritis	Disease	D005921
+7834920	70	78	rifampin	Chemical	D012293
+7834920	91	113	pulmonary tuberculosis	Disease	D014397
+7834920	194	212	glomerulonephritis	Disease	D005921
+7834920	239	247	rifampin	Chemical	D012293
+7834920	359	367	rifampin	Chemical	D012293
+7834920	372	381	isoniazid	Chemical	D007538
+7834920	386	408	pulmonary tuberculosis	Disease	D014397
+7834920	462	475	renal failure	Disease	D051437
+7834920	545	563	glomerulonephritis	Disease	D005921
+7834920	709	727	glomerulonephritis	Disease	D005921
+7834920	829	847	glomerulonephritis	Disease	D005921
+7834920	877	895	glomerulonephritis	Disease	D005921
+7834920	922	930	rifampin	Chemical	D012293
+7834920	CID	D012293	D005921
+7834920	CID	D012293	D051437
+
+7881871|t|Time course of lipid peroxidation in puromycin aminonucleoside-induced nephropathy.
+7881871|a|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.
+7881871	37	62	puromycin aminonucleoside	Chemical	D011692
+7881871	71	82	nephropathy	Disease	D007674
+7881871	93	99	oxygen	Chemical	D010100
+7881871	158	183	puromycin aminonucleoside	Chemical	D011692
+7881871	185	188	PAN	Chemical	D011692
+7881871	198	209	nephropathy	Disease	D007674
+7881871	256	267	proteinuria	Disease	D011507
+7881871	340	351	proteinuria	Disease	D011507
+7881871	428	453	puromycin aminonucleoside	Chemical	D011692
+7881871	456	459	PAN	Chemical	D011692
+7881871	816	835	thiobarbituric acid	Chemical	C029684
+7881871	857	868	Proteinuria	Disease	D011507
+7881871	1105	1123	proteinuric injury	Disease	D011507
+7881871	1127	1130	PAN	Chemical	D011692
+7881871	1131	1142	nephropathy	Disease	D007674
+7881871	CID	D011692	D007674
+7881871	CID	D011692	D011507
+
+7930386|t|Clomipramine-induced sleep disturbance does not impair its prolactin-releasing action.
+7930386|a|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.
+7930386	0	12	Clomipramine	Chemical	D002997
+7930386	21	38	sleep disturbance	Disease	D012893
+7930386	143	160	sleep disturbance	Disease	D012893
+7930386	173	185	clomipramine	Chemical	D002997
+7930386	497	509	clomipramine	Chemical	D002997
+7930386	927	939	clomipramine	Chemical	D002997
+7930386	1292	1309	sleep disturbance	Disease	D012893
+7930386	1548	1560	clomipramine	Chemical	D002997
+7930386	CID	D002997	D012893
+
+7988234|t|Angioedema following the intravenous administration of metoprolol.
+7988234|a|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.
+7988234	0	10	Angioedema	Disease	D000799
+7988234	55	65	metoprolol	Chemical	D008790
+7988234	129	144	pulmonary edema	Disease	D011654
+7988234	158	168	chest pain	Disease	D002637
+7988234	221	244	coronary artery disease	Disease	D003324
+7988234	259	281	myocardial infarctions	Disease	D009203
+7988234	283	295	hypertension	Disease	D006973
+7988234	301	318	diabetes mellitus	Disease	D003920
+7988234	333	343	angioedema	Disease	D000799
+7988234	357	367	lisinopril	Chemical	D017706
+7988234	426	437	angiotensin	Chemical	D000809
+7988234	605	615	metoprolol	Chemical	D008790
+7988234	647	657	angioedema	Disease	D000799
+7988234	663	673	angioedema	Disease	D000799
+7988234	714	722	steroids	Chemical	D013256
+7988234	727	742	diphenhydramine	Chemical	D004155
+7988234	CID	D008790	D000799
+7988234	CID	D017706	D000799
+
+8073369|t|Effect of coniine on the developing chick embryo.
+8073369|a|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.
+8073369	10	17	coniine	Chemical	C007112
+8073369	50	57	Coniine	Chemical	C007112
+8073369	191	205	arthrogryposis	Disease	D001176
+8073369	263	270	coniine	Chemical	C007112
+8073369	293	307	arthrogryposis	Disease	D001176
+8073369	436	443	coniine	Chemical	C007112
+8073369	448	456	nicotine	Chemical	D009538
+8073369	500	507	coniine	Chemical	C007112
+8073369	512	520	nicotine	Chemical	D009538
+8073369	645	657	deformations	Disease	D009140
+8073369	722	730	nicotine	Chemical	D009538
+8073369	787	794	coniine	Chemical	C007112
+8073369	820	832	deformations	Disease	D009140
+8073369	848	855	coniine	Chemical	C007112
+8073369	860	868	nicotine	Chemical	D009538
+8073369	882	932	excessive flexion or extension of one or more toes	Disease	D009140
+8073369	1080	1098	cranial hemorrhage	Disease	D002543
+8073369	1115	1123	nicotine	Chemical	D009538
+8073369	1226	1233	coniine	Chemical	C007112
+8073369	1238	1246	nicotine	Chemical	D009538
+8073369	1369	1376	coniine	Chemical	C007112
+8073369	1469	1477	nicotine	Chemical	D009538
+8073369	1591	1598	coniine	Chemical	C007112
+8073369	1607	1621	arthrogryposis	Disease	D001176
+8073369	CID	D009538	D001176
+8073369	CID	C007112	D001176
+8073369	CID	D009538	D002543
+
+8302922|t|Epidural blood flow during prostaglandin E1 or trimethaphan induced hypotension.
+8302922|a|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.
+8302922	27	43	prostaglandin E1	Chemical	D000527
+8302922	47	59	trimethaphan	Chemical	D014294
+8302922	68	79	hypotension	Disease	D007022
+8302922	107	123	prostaglandin E1	Chemical	D000527
+8302922	125	129	PGE1	Chemical	D000527
+8302922	134	146	trimethaphan	Chemical	D014294
+8302922	148	151	TMP	Chemical	D014294
+8302922	161	172	hypotension	Disease	D007022
+8302922	342	352	isoflurane	Chemical	D007530
+8302922	413	417	PGE1	Chemical	D000527
+8302922	464	467	TMP	Chemical	D014294
+8302922	636	647	hypotensive	Disease	D007022
+8302922	731	735	PGE1	Chemical	D000527
+8302922	739	742	TMP	Chemical	D014294
+8302922	867	878	hypotension	Disease	D007022
+8302922	886	890	PGE1	Chemical	D000527
+8302922	1024	1028	PGE1	Chemical	D000527
+8302922	1053	1056	TMP	Chemical	D014294
+8302922	1128	1131	TMP	Chemical	D014294
+8302922	1291	1295	PGE1	Chemical	D000527
+8302922	1317	1320	TMP	Chemical	D014294
+8302922	1325	1336	hypotensive	Disease	D007022
+8302922	1375	1378	TMP	Chemical	D014294
+8302922	CID	D014294	D007022
+8302922	CID	D000527	D007022
+
+8410052|t|Immunohistochemical studies with antibodies to neurofilament proteins on axonal damage in experimental focal lesions in rat.
+8410052|a|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.
+8410052	73	86	axonal damage	Disease	D001480
+8410052	285	298	axonal injury	Disease	D001480
+8410052	349	369	injury in the cortex	Disease	D001480
+8410052	398	405	lactate	Chemical	D019344
+8410052	456	500	Infarcts in substantia nigra pars reticulata	Disease	D002544
+8410052	526	537	pilocarpine	Chemical	D010862
+8410052	546	564	status epilepticus	Disease	D013226
+8410052	904	917	axonal damage	Disease	D001480
+8410052	942	951	traumatic	Disease	D014947
+8410052	CID	D010862	D013226
+8410052	CID	D010862	D002544
+8410052	CID	D010862	D001480
+
+8423889|t|Increase of Parkinson disability after fluoxetine medication.
+8423889|a|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.
+8423889	12	32	Parkinson disability	Disease	D009069
+8423889	39	49	fluoxetine	Chemical	D005473
+8423889	62	72	Depression	Disease	D003866
+8423889	104	123	Parkinson's disease	Disease	D010300
+8423889	159	175	motor disability	Disease	D009069
+8423889	198	228	idiopathic Parkinson's disease	Disease	D010300
+8423889	251	265	antidepressant	Chemical	D000928
+8423889	266	276	fluoxetine	Chemical	D005473
+8423889	319	327	dopamine	Chemical	D004298
+8423889	353	363	fluoxetine	Chemical	D005473
+8423889	367	386	Parkinson's disease	Disease	D010300
+8423889	CID	D005473	D009069
+
+8682684|t|Acetaminophen-induced hypotension.
+8682684|a|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.
+8682684	0	13	Acetaminophen	Chemical	D000082
+8682684	22	33	hypotension	Disease	D007022
+8682684	71	84	acetaminophen	Chemical	D000082
+8682684	177	190	acetaminophen	Chemical	D000082
+8682684	202	227	cardiovascular toxicities	Disease	D002318
+8682684	250	263	acetaminophen	Chemical	D000082
+8682684	309	320	anaphylaxis	Disease	D000707
+8682684	332	343	hypotension	Disease	D007022
+8682684	398	412	critically ill	Disease	D016638
+8682684	452	463	hypotension	Disease	D007022
+8682684	511	524	acetaminophen	Chemical	D000082
+8682684	544	562	allergic reactions	Disease	D004342
+8682684	599	610	hypotensive	Disease	D007022
+8682684	737	750	acetaminophen	Chemical	D000082
+8682684	768	779	hypotension	Disease	D007022
+8682684	CID	D000082	D007022
+
+9625142|t|Acute hepatitis, autoimmune hemolytic anemia, and erythroblastocytopenia induced by ceftriaxone.
+9625142|a|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.
+9625142	6	15	hepatitis	Disease	D056486
+9625142	17	44	autoimmune hemolytic anemia	Disease	D000744
+9625142	50	72	erythroblastocytopenia	Disease	-1
+9625142	84	95	ceftriaxone	Chemical	D002443
+9625142	130	139	hepatitis	Disease	D056486
+9625142	169	180	ceftriaxone	Chemical	D002443
+9625142	262	273	beta lactam	Chemical	D047090
+9625142	324	333	bilirubin	Chemical	D001663
+9625142	390	417	autoimmune hemolytic anemia	Disease	D000744
+9625142	422	444	erythroblastocytopenia	Disease	-1
+9625142	474	482	steroids	Chemical	D013256
+9625142	626	637	beta lactam	Chemical	D047090
+9625142	CID	D002443	D000744
+9625142	CID	D002443	D056486
+
+9766615|t|Adverse effects of the atypical antipsychotics. Collaborative Working Group on Clinical Trial Evaluations.
+9766615|a|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.
+9766615	568	591	extrapyramidal symptoms	Disease	D001480
+9766615	593	596	EPS	Disease	D001480
+9766615	599	617	tardive dyskinesia	Disease	D004409
+9766615	709	732	orthostatic hypotension	Disease	D007024
+9766615	781	799	sexual dysfunction	Disease	D012735
+9766615	805	816	weight gain	Disease	D015430
+9766615	865	868	EPS	Disease	D001480
+9766615	972	983	weight gain	Disease	D015430
+9766615	985	1003	sexual dysfunction	Disease	D012735
+9766615	1030	1037	seizure	Disease	D012640
+9766615	1059	1068	clozapine	Chemical	D003024
+9766615	1075	1090	agranulocytosis	Disease	D000380
+9766615	1092	1101	clozapine	Chemical	D003024
+9766615	CID	D003024	D000380
+
+10193204|t|Effects of tetrandrine and fangchinoline on experimental thrombosis in mice and human platelet aggregation.
+10193204|a|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.
+10193204	11	22	tetrandrine	Chemical	C009438
+10193204	27	40	fangchinoline	Chemical	C060802
+10193204	57	67	thrombosis	Disease	D013927
+10193204	86	106	platelet aggregation	Disease	D001791
+10193204	108	119	Tetrandrine	Chemical	C009438
+10193204	121	124	TET	Chemical	C009438
+10193204	130	143	fangchinoline	Chemical	C060802
+10193204	145	148	FAN	Chemical	C060802
+10193204	195	216	bisbenzylisoquinoline	Chemical	D044182
+10193204	291	294	TET	Chemical	C009438
+10193204	299	302	FAN	Chemical	C060802
+10193204	323	333	thrombosis	Disease	D013927
+10193204	359	370	epinephrine	Chemical	D004837
+10193204	372	374	EP	Chemical	D004837
+10193204	389	409	platelet aggregation	Disease	D001791
+10193204	414	431	blood coagulation	Disease	D001778
+10193204	503	506	TET	Chemical	C009438
+10193204	511	514	FAN	Chemical	C060802
+10193204	548	558	thrombosis	Disease	D013927
+10193204	595	615	acetylsalicylic acid	Chemical	D001241
+10193204	617	620	ASA	Chemical	D001241
+10193204	706	727	platelet aggregations	Disease	D001791
+10193204	767	770	TET	Chemical	C009438
+10193204	775	778	FAN	Chemical	C060802
+10193204	841	844	TET	Chemical	C009438
+10193204	849	852	FAN	Chemical	C060802
+10193204	1082	1085	TET	Chemical	C009438
+10193204	1090	1093	FAN	Chemical	C060802
+10193204	CID	D004837	D013927
+
+10526274|t|Gemcitabine plus vinorelbine in nonsmall cell lung carcinoma patients age 70 years or older or patients who cannot receive cisplatin. Oncopaz Cooperative Group.
+10526274|a|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.
+10526274	0	11	Gemcitabine	Chemical	C056507
+10526274	17	28	vinorelbine	Chemical	C030852
+10526274	32	60	nonsmall cell lung carcinoma	Disease	D002289
+10526274	123	132	cisplatin	Chemical	D002945
+10526274	200	228	nonsmall cell lung carcinoma	Disease	D002289
+10526274	230	235	NSCLC	Disease	D002289
+10526274	319	327	toxicity	Disease	D064420
+10526274	426	437	vinorelbine	Chemical	C030852
+10526274	439	442	VNB	Chemical	C030852
+10526274	447	458	gemcitabine	Chemical	C056507
+10526274	460	463	GEM	Chemical	C056507
+10526274	539	547	toxicity	Disease	D064420
+10526274	635	643	toxicity	Disease	D064420
+10526274	666	669	GEM	Chemical	C056507
+10526274	674	677	VNB	Chemical	C030852
+10526274	712	717	NSCLC	Disease	D002289
+10526274	767	776	cisplatin	Chemical	D002945
+10526274	835	840	NSCLC	Disease	D002289
+10526274	963	972	cisplatin	Chemical	D002945
+10526274	1019	1027	toxicity	Disease	D064420
+10526274	1056	1059	VNB	Chemical	C030852
+10526274	1078	1081	GEM	Chemical	C056507
+10526274	1795	1803	Toxicity	Disease	D064420
+10526274	1873	1884	neutropenia	Disease	D009503
+10526274	1916	1932	thrombocytopenia	Disease	D013921
+10526274	1966	1979	neurotoxicity	Disease	D020258
+10526274	2008	2019	neutropenia	Disease	D009503
+10526274	2033	2039	sepsis	Disease	D018805
+10526274	2095	2106	neutropenia	Disease	D009503
+10526274	2236	2239	GEM	Chemical	C056507
+10526274	2244	2247	VNB	Chemical	C030852
+10526274	2365	2381	myelosuppression	Disease	D001855
+10526274	2558	2566	toxicity	Disease	D064420
+10526274	2613	2618	NSCLC	Disease	D002289
+10526274	CID	C056507	D013921
+10526274	CID	C030852	D013921
+10526274	CID	C056507	D020258
+10526274	CID	C030852	D009503
+10526274	CID	C056507	D009503
+10526274	CID	C030852	D020258
+
+10669626|t|Warfarin-induced artery calcification is accelerated by growth and vitamin D.
+10669626|a|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.
+10669626	0	8	Warfarin	Chemical	D014859
+10669626	17	37	artery calcification	Disease	D061205
+10669626	67	76	vitamin D	Chemical	D014807
+10669626	126	135	vitamin D	Chemical	D014807
+10669626	168	188	artery calcification	Disease	D061205
+10669626	223	231	Warfarin	Chemical	D014859
+10669626	288	301	calcification	Disease	D002114
+10669626	476	496	artery calcification	Disease	D061205
+10669626	500	508	Warfarin	Chemical	D014859
+10669626	550	558	Warfarin	Chemical	D014859
+10669626	580	607	calcification of the artery	Disease	D061205
+10669626	658	671	calcification	Disease	D002114
+10669626	708	728	artery calcification	Disease	D061205
+10669626	796	804	Warfarin	Chemical	D014859
+10669626	864	872	Warfarin	Chemical	D014859
+10669626	881	901	artery calcification	Disease	D061205
+10669626	1112	1120	Warfarin	Chemical	D014859
+10669626	1144	1171	calcification of the artery	Disease	D061205
+10669626	1223	1243	artery calcification	Disease	D061205
+10669626	1345	1365	artery calcification	Disease	D061205
+10669626	1475	1484	phosphate	Chemical	D010710
+10669626	1507	1527	artery calcification	Disease	D061205
+10669626	1561	1570	phosphate	Chemical	D010710
+10669626	1658	1666	Warfarin	Chemical	D014859
+10669626	1675	1695	artery calcification	Disease	D061205
+10669626	1836	1844	Warfarin	Chemical	D014859
+10669626	1853	1873	artery calcification	Disease	D061205
+10669626	1907	1916	phosphate	Chemical	D010710
+10669626	1993	2002	vitamin D	Chemical	D014807
+10669626	2007	2015	Warfarin	Chemical	D014859
+10669626	2019	2039	artery calcification	Disease	D061205
+10669626	2055	2064	vitamin D	Chemical	D014807
+10669626	2084	2111	calcification of the artery	Disease	D061205
+10669626	2165	2174	vitamin K	Chemical	D014812
+10669626	2186	2194	Warfarin	Chemical	D014859
+10669626	2219	2246	calcification of the artery	Disease	D061205
+10669626	2420	2428	Warfarin	Chemical	D014859
+10669626	2481	2494	calcification	Disease	D002114
+10669626	2511	2520	vitamin D	Chemical	D014807
+10669626	2600	2609	vitamin D	Chemical	D014807
+10669626	2618	2638	artery calcification	Disease	D061205
+10669626	2657	2666	vitamin D	Chemical	D014807
+10669626	2698	2705	calcium	Chemical	D002118
+10669626	2727	2736	vitamin D	Chemical	D014807
+10669626	2748	2768	artery calcification	Disease	D061205
+10669626	2797	2804	calcium	Chemical	D002118
+10669626	2814	2822	Warfarin	Chemical	D014859
+10669626	2873	2880	calcium	Chemical	D002118
+10669626	2893	2902	vitamin D	Chemical	D014807
+10669626	2924	2932	Warfarin	Chemical	D014859
+10669626	2937	2946	vitamin D	Chemical	D014807
+10669626	2997	3005	Warfarin	Chemical	D014859
+10669626	3055	3068	calcification	Disease	D002114
+10669626	3136	3156	artery calcification	Disease	D061205
+10669626	3178	3187	vitamin D	Chemical	D014807
+10669626	3193	3201	Warfarin	Chemical	D014859
+10669626	3281	3299	gamma-carboxylated	Chemical	D015055
+10669626	3347	3369	gamma-carboxyglutamate	Chemical	D015055
+10669626	3447	3460	calcification	Disease	D002114
+10669626	3518	3531	calcification	Disease	D002114
+10669626	CID	D014859	D061205
+
+11379838|t|Antidepressant-induced mania in bipolar patients: identification of risk factors.
+11379838|a|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.
+11379838	0	14	Antidepressant	Chemical	D000928
+11379838	23	28	mania	Disease	D001714
+11379838	32	39	bipolar	Disease	D001714
+11379838	140	145	mania	Disease	D001714
+11379838	162	177	antidepressants	Chemical	D000928
+11379838	260	278	bipolar depression	Disease	D001714
+11379838	344	360	bipolar disorder	Disease	D001714
+11379838	543	548	manic	Disease	D001714
+11379838	552	561	hypomanic	Disease	D001714
+11379838	658	674	DSM-IV bipolar I	Disease	D001714
+11379838	679	689	bipolar II	Disease	D001714
+11379838	711	716	manic	Disease	D001714
+11379838	735	749	antidepressant	Chemical	D000928
+11379838	794	808	antidepressant	Chemical	D000928
+11379838	849	878	serotonin reuptake inhibitors	Chemical	D017367
+11379838	880	885	SSRIs	Chemical	D017367
+11379838	923	930	lithium	Chemical	D008094
+11379838	1131	1140	hypomania	Disease	D001714
+11379838	1144	1149	mania	Disease	D001714
+11379838	1244	1249	SSRIs	Chemical	D017367
+11379838	1283	1288	manic	Disease	D001714
+11379838	1327	1336	hypomanic	Disease	D001714
+11379838	1368	1377	bipolar I	Disease	D001714
+11379838	1382	1392	bipolar II	Disease	D001714
+11379838	1663	1670	lithium	Chemical	D008094
+11379838	1717	1724	lithium	Chemical	D008094
+11379838	1770	1775	manic	Disease	D001714
+11379838	2060	2074	antidepressant	Chemical	D000928
+11379838	2101	2108	lithium	Chemical	D008094
+11379838	CID	D000928	D001714
+11379838	CID	D017367	D001714
+
+11419773|t|Caffeine-induced cardiac arrhythmia: an unrecognised danger of healthfood products.
+11419773|a|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.
+11419773	0	8	Caffeine	Chemical	D002110
+11419773	17	35	cardiac arrhythmia	Disease	D001145
+11419773	134	155	mitral valve prolapse	Disease	D008945
+11419773	182	206	ventricular fibrillation	Disease	D014693
+11419773	298	306	caffeine	Chemical	D002110
+11419773	CID	D002110	D014693
+
+11581460|t|Bladder retention of urine as a result of continuous intravenous infusion of fentanyl: 2 case reports.
+11581460|a|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.
+11581460	8	26	retention of urine	Disease	D016055
+11581460	77	85	fentanyl	Chemical	D005283
+11581460	177	181	pain	Disease	D010146
+11581460	347	355	Fentanyl	Chemical	D005283
+11581460	499	507	fentanyl	Chemical	D005283
+11581460	531	550	chest wall rigidity	Disease	D009127
+11581460	552	563	hypotension	Disease	D007022
+11581460	565	587	respiratory depression	Disease	D012131
+11581460	593	604	bradycardia	Disease	D001919
+11581460	623	648	urinary bladder retention	Disease	D001745
+11581460	701	715	hydronephrosis	Disease	D006869
+11581460	754	762	fentanyl	Chemical	D005283
+11581460	CID	D005283	D012131
+11581460	CID	D005283	D007022
+11581460	CID	D005283	D001745
+11581460	CID	D005283	D001919
+11581460	CID	D005283	D016055
+
+11706060|t|Combined antiretroviral therapy causes cardiomyopathy and elevates plasma lactate in transgenic AIDS mice.
+11706060|a|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.
+11706060	39	53	cardiomyopathy	Disease	D009202
+11706060	74	81	lactate	Chemical	D019344
+11706060	96	100	AIDS	Disease	D000163
+11706060	169	183	cardiomyopathy	Disease	D009202
+11706060	185	187	CM	Disease	D009202
+11706060	212	219	lactate	Chemical	D019344
+11706060	221	223	LA	Chemical	D019344
+11706060	228	232	AIDS	Disease	D000163
+11706060	255	280	mitochondrial dysfunction	Disease	D028361
+11706060	369	373	AIDS	Disease	D000163
+11706060	479	489	zidovudine	Chemical	D015215
+11706060	491	501	lamivudine	Chemical	D019259
+11706060	507	516	indinavir	Chemical	D019469
+11706060	678	680	CM	Disease	D009202
+11706060	757	764	calcium	Chemical	D002118
+11706060	811	813	LA	Chemical	D019344
+11706060	1124	1126	LA	Chemical	D019344
+11706060	1490	1492	CM	Disease	D009202
+11706060	1507	1509	LA	Chemical	D019344
+11706060	1513	1517	AIDS	Disease	D000163
+11706060	CID	D019469	D009202
+11706060	CID	D019259	D009202
+11706060	CID	D015215	D009202
+
+11752354|t|Oral contraceptives and the risk of myocardial infarction.
+11752354|a|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.
+11752354	0	19	Oral contraceptives	Chemical	D003276
+11752354	36	57	myocardial infarction	Disease	D009203
+11752354	105	124	oral contraceptives	Chemical	D003276
+11752354	141	162	myocardial infarction	Disease	D009203
+11752354	268	279	progestagen	Chemical	D011372
+11752354	316	327	desogestrel	Chemical	D017135
+11752354	331	340	gestodene	Chemical	C033273
+11752354	371	385	levonorgestrel	Chemical	D016912
+11752354	387	406	oral contraceptives	Chemical	D003276
+11752354	420	428	estrogen	Chemical	D004967
+11752354	633	654	myocardial infarction	Disease	D009203
+11752354	717	738	myocardial infarction	Disease	D009203
+11752354	859	877	oral-contraceptive	Chemical	D003276
+11752354	1077	1098	myocardial infarction	Disease	D009203
+11752354	1141	1159	oral contraceptive	Chemical	D003276
+11752354	1358	1377	oral contraceptives	Chemical	D003276
+11752354	1469	1488	oral contraceptives	Chemical	D003276
+11752354	1511	1530	oral contraceptives	Chemical	D003276
+11752354	1747	1768	myocardial infarction	Disease	D009203
+11752354	1822	1841	oral contraceptives	Chemical	D003276
+11752354	1899	1918	oral contraceptives	Chemical	D003276
+11752354	2023	2042	oral contraceptives	Chemical	D003276
+11752354	2056	2077	myocardial infarction	Disease	D009203
+11752354	2111	2130	oral contraceptives	Chemical	D003276
+11752354	CID	D003276	D009203
+
+12369736|t|Effects of 5-HT1B receptor ligands microinjected into the accumbal shell or core on the cocaine-induced locomotor hyperactivity in rats.
+12369736|a|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.
+12369736	88	95	cocaine	Chemical	D003042
+12369736	104	127	locomotor hyperactivity	Disease	D009069
+12369736	308	331	locomotor hyperactivity	Disease	D009069
+12369736	343	350	cocaine	Chemical	D003042
+12369736	488	496	GR 55562	Chemical	C103477
+12369736	536	544	CP 93129	Chemical	C065046
+12369736	618	626	GR 55562	Chemical	C103477
+12369736	651	659	CP 93129	Chemical	C065046
+12369736	731	738	cocaine	Chemical	D003042
+12369736	806	814	GR 55562	Chemical	C103477
+12369736	881	888	cocaine	Chemical	D003042
+12369736	946	969	locomotor hyperactivity	Disease	D009069
+12369736	1042	1050	GR 55562	Chemical	C103477
+12369736	1141	1148	cocaine	Chemical	D003042
+12369736	1150	1158	CP 93129	Chemical	C065046
+12369736	1215	1222	cocaine	Chemical	D003042
+12369736	1375	1383	GR 55562	Chemical	C103477
+12369736	1428	1435	cocaine	Chemical	D003042
+12369736	1444	1459	hyperlocomotion	Disease	D009069
+12369736	1656	1664	GR 55562	Chemical	C103477
+12369736	1679	1687	CP 93129	Chemical	C065046
+12369736	CID	D003042	D009069
+12369736	CID	C065046	D009069
+
+12639165|t|Ticlopidine-induced cholestatic hepatitis.
+12639165|a|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.
+12639165	0	11	Ticlopidine	Chemical	D013988
+12639165	20	41	cholestatic hepatitis	Disease	D002779|D056486	cholestatic|hepatitis
+12639165	75	86	ticlopidine	Chemical	D013988
+12639165	95	116	cholestatic hepatitis	Disease	D002779|D056486	cholestatic|hepatitis
+12639165	275	296	cholestatic hepatitis	Disease	D002779|D056486	cholestatic|hepatitis
+12639165	313	324	ticlopidine	Chemical	D013988
+12639165	474	485	ticlopidine	Chemical	D013988
+12639165	570	591	Cholestatic hepatitis	Disease	D002779|D056486	Cholestatic|hepatitis
+12639165	641	652	ticlopidine	Chemical	D013988
+12639165	745	753	jaundice	Disease	D007565
+12639165	779	790	ticlopidine	Chemical	D013988
+12639165	849	870	cholestatic hepatitis	Disease	D002779|D056486	cholestatic|hepatitis
+12639165	922	931	Hepatitis	Disease	D056486
+12639165	1181	1192	ticlopidine	Chemical	D013988
+12639165	1217	1228	ticlopidine	Chemical	D013988
+12639165	1237	1248	cholestasis	Disease	D002779
+12639165	1310	1324	hepatotoxicity	Disease	D056486
+12639165	1399	1420	Cholestatic hepatitis	Disease	D002779|D056486	Cholestatic|hepatitis
+12639165	1449	1460	ticlopidine	Chemical	D013988
+12639165	1671	1682	ticlopidine	Chemical	D013988
+12639165	1733	1744	clopidogrel	Chemical	C055162
+12639165	CID	D013988	D007565
+12639165	CID	D013988	D002779
+12639165	CID	D013988	D056486
+
+12653683|t|Epithelial sodium channel (ENaC) subunit mRNA and protein expression in rats with puromycin aminonucleoside-induced nephrotic syndrome.
+12653683|a|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.
+12653683	11	17	sodium	Chemical	D012964
+12653683	82	107	puromycin aminonucleoside	Chemical	D011692
+12653683	116	134	nephrotic syndrome	Disease	D009404
+12653683	152	170	nephrotic syndrome	Disease	D009404
+12653683	180	186	sodium	Chemical	D012964
+12653683	387	393	sodium	Chemical	D012964
+12653683	422	428	sodium	Chemical	D012964
+12653683	509	534	puromycin aminonucleoside	Chemical	D011692
+12653683	536	539	PAN	Chemical	D011692
+12653683	549	567	nephrotic syndrome	Disease	D009404
+12653683	597	603	sodium	Chemical	D012964
+12653683	622	633	aldosterone	Chemical	D000450
+12653683	652	663	proteinuria	Disease	D011507
+12653683	742	745	PAN	Chemical	D011692
+12653683	972	978	sodium	Chemical	D012964
+12653683	1011	1022	proteinuria	Disease	D011507
+12653683	1071	1077	Sodium	Chemical	D012964
+12653683	1122	1125	PAN	Chemical	D011692
+12653683	1231	1237	sodium	Chemical	D012964
+12653683	1388	1399	aldosterone	Chemical	D000450
+12653683	1448	1454	sodium	Chemical	D012964
+12653683	1568	1571	PAN	Chemical	D011692
+12653683	1580	1586	sodium	Chemical	D012964
+12653683	1723	1726	PAN	Chemical	D011692
+12653683	1735	1753	nephrotic syndrome	Disease	D009404
+12653683	1808	1819	aldosterone	Chemical	D000450
+12653683	CID	D011692	D011507
+12653683	CID	D011692	D009404
+
+14659530|t|NO-induced migraine attack: strong increase in plasma calcitonin gene-related peptide (CGRP) concentration and negative correlation with platelet serotonin release.
+14659530|a|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.
+14659530	0	2	NO	Chemical	D009569
+14659530	11	19	migraine	Disease	D008881
+14659530	54	85	calcitonin gene-related peptide	Chemical	D015740
+14659530	87	91	CGRP	Chemical	D015740
+14659530	146	155	serotonin	Chemical	D012701
+14659530	235	266	calcitonin gene-related peptide	Chemical	D015740
+14659530	268	272	CGRP	Chemical	D015740
+14659530	301	310	serotonin	Chemical	D012701
+14659530	312	331	5-hydroxytriptamine	Chemical	D012701
+14659530	333	337	5-HT	Chemical	D012701
+14659530	368	376	headache	Disease	D006261
+14659530	401	409	migraine	Disease	D008881
+14659530	429	442	nitroglycerin	Chemical	D005996
+14659530	459	485	migraineurs (without aura)	Disease	D020326
+14659530	543	556	nitroglycerin	Chemical	D005996
+14659530	670	683	nitroglycerin	Chemical	D005996
+14659530	743	751	migraine	Disease	D008881
+14659530	825	833	migraine	Disease	D008881
+14659530	896	900	CGRP	Chemical	D015740
+14659530	959	967	migraine	Disease	D008881
+14659530	1027	1035	migraine	Disease	D008881
+14659530	1118	1126	migraine	Disease	D008881
+14659530	1127	1135	headache	Disease	D006261
+14659530	1173	1177	CGRP	Chemical	D015740
+14659530	1227	1235	headache	Disease	D006261
+14659530	1264	1272	migraine	Disease	D008881
+14659530	1287	1291	CGRP	Chemical	D015740
+14659530	1344	1348	5-HT	Chemical	D012701
+14659530	1406	1414	migraine	Disease	D008881
+14659530	1432	1441	serotonin	Chemical	D012701
+14659530	1489	1502	nitroglycerin	Chemical	D005996
+14659530	1523	1531	migraine	Disease	D008881
+14659530	1594	1602	migraine	Disease	D008881
+14659530	1647	1651	CGRP	Chemical	D015740
+14659530	1711	1719	migraine	Disease	D008881
+14659530	1720	1728	headache	Disease	D006261
+14659530	1768	1772	CGRP	Chemical	D015740
+14659530	1777	1785	migraine	Disease	D008881
+14659530	1800	1809	serotonin	Chemical	D012701
+14659530	1850	1858	migraine	Disease	D008881
+14659530	1887	1895	headache	Disease	D006261
+14659530	1916	1920	CGRP	Chemical	D015740
+14659530	CID	D005996	D020326
+14659530	CID	D009569	D020326
+
+15804801|t|Coronary aneurysm after implantation of a paclitaxel-eluting stent.
+15804801|a|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.
+15804801	0	17	Coronary aneurysm	Disease	D003323
+15804801	42	52	paclitaxel	Chemical	D017239
+15804801	81	98	coronary aneurysm	Disease	D003323
+15804801	290	298	aneurysm	Disease	D000783
+15804801	341	351	thrombosis	Disease	D013927
+15804801	355	369	vessel rupture	Disease	-1
+15804801	416	433	coronary aneurysm	Disease	D003323
+15804801	490	500	paclitaxel	Chemical	D017239
+15804801	553	561	aneurysm	Disease	D000783
+15804801	734	742	aneurysm	Disease	D000783
+15804801	CID	D017239	D003323
+
+16160878|t|Behavioral effects of urotensin-II centrally administered in mice.
+16160878|a|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.
+16160878	22	34	urotensin-II	Chemical	D014579
+16160878	67	79	Urotensin-II	Chemical	D014579
+16160878	81	85	U-II	Chemical	D014579
+16160878	197	201	U-II	Chemical	D014579
+16160878	209	221	hypertension	Disease	D006973
+16160878	226	237	bradycardia	Disease	D001919
+16160878	348	352	U-II	Chemical	D014579
+16160878	453	457	U-II	Chemical	D014579
+16160878	551	555	U-II	Chemical	D014579
+16160878	1031	1035	U-II	Chemical	D014579
+16160878	1276	1280	U-II	Chemical	D014579
+16160878	1329	1340	apomorphine	Chemical	D001058
+16160878	1349	1364	penile erection	Disease	D010409
+16160878	1414	1428	corticosterone	Chemical	D003345
+16160878	1513	1517	U-II	Chemical	D014579
+16160878	1630	1634	U-II	Chemical	D014579
+16160878	1670	1691	psychiatric disorders	Disease	D001523
+16160878	CID	D001058	D010409
+
+16274958|t|Recurrent dysphonia and acitretin.
+16274958|a|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.
+16274958	10	19	dysphonia	Disease	D055154
+16274958	24	33	acitretin	Chemical	D017255
+16274958	80	89	dysphonia	Disease	D055154
+16274958	115	124	acitretin	Chemical	D017255
+16274958	199	208	acitretin	Chemical	D017255
+16274958	271	280	acitretin	Chemical	D017255
+16274958	289	298	dysphonia	Disease	D055154
+16274958	CID	D017255	D055154
+
+16330766|t|Pharmacological modulation of pain-related brain activity during normal and central sensitization states in humans.
+16330766|a|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.
+16330766	30	34	pain	Disease	D010146
+16330766	259	263	pain	Disease	D010146
+16330766	300	313	tissue injury	Disease	D017695
+16330766	315	337	secondary hyperalgesia	Disease	D006930
+16330766	340	362	Secondary hyperalgesia	Disease	D006930
+16330766	400	423	neurogenic hyperalgesia	Disease	D006930
+16330766	441	457	neuropathic pain	Disease	D009437
+16330766	542	554	hyperalgesia	Disease	D006930
+16330766	679	689	gabapentin	Chemical	C040029
+16330766	711	727	neuropathic pain	Disease	D009437
+16330766	917	927	gabapentin	Chemical	C040029
+16330766	1034	1043	capsaicin	Chemical	D002211
+16330766	1052	1074	secondary hyperalgesia	Disease	D006930
+16330766	1088	1098	gabapentin	Chemical	C040029
+16330766	1166	1176	gabapentin	Chemical	C040029
+16330766	1303	1313	gabapentin	Chemical	C040029
+16330766	1396	1406	gabapentin	Chemical	C040029
+16330766	1666	1676	gabapentin	Chemical	C040029
+16330766	1846	1856	gabapentin	Chemical	C040029
+16330766	CID	D002211	D006930
+
+16574712|t|MDMA polydrug users show process-specific central executive impairments coupled with impaired social and emotional judgement processes.
+16574712|a|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.
+16574712	0	4	MDMA	Chemical	D018817
+16574712	85	134	impaired social and emotional judgement processes	Disease	D003072
+16574712	160	175	memory deficits	Disease	D008569
+16574712	207	211	MDMA	Chemical	D018817
+16574712	213	246	3,4-methylenedioxymethamphetamine	Chemical	D018817
+16574712	248	255	ecstasy	Chemical	D018817
+16574712	306	310	MDMA	Chemical	D018817
+16574712	501	508	ecstasy	Chemical	D018817
+16574712	535	542	ecstasy	Chemical	D018817
+16574712	865	869	MDMA	Chemical	D018817
+16574712	894	898	MDMA	Chemical	D018817
+16574712	1246	1253	ecstasy	Chemical	D018817
+16574712	CID	D018817	D003072
+
+17111419|t|Severe citrate toxicity complicating volunteer apheresis platelet donation.
+17111419|a|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.
+17111419	7	14	citrate	Chemical	C102006
+17111419	15	23	toxicity	Disease	D064420
+17111419	103	110	citrate	Chemical	C102006
+17111419	111	119	toxicity	Disease	D064420
+17111419	287	299	hypertension	Disease	D006973
+17111419	301	315	hyperlipidemia	Disease	D006949
+17111419	321	331	depression	Disease	D003866
+17111419	363	373	bumetanide	Chemical	D002034
+17111419	375	386	pravastatin	Chemical	D017035
+17111419	392	402	paroxetine	Chemical	D017374
+17111419	587	593	tetany	Disease	D013746
+17111419	632	649	calcium gluconate	Chemical	D002125
+17111419	669	688	muscle contractions	Disease	C536214
+17111419	794	801	calcium	Chemical	D002118
+17111419	815	829	sodium citrate	Chemical	C102006
+17111419	878	890	hypocalcemia	Disease	D006996
+17111419	950	960	bumetanide	Chemical	D002034
+17111419	966	979	loop diuretic	Chemical	D049994
+17111419	1007	1019	hypocalcemia	Disease	D006996
+17111419	1114	1126	hypocalcemia	Disease	D006996
+17111419	1182	1189	citrate	Chemical	C102006
+17111419	1190	1198	toxicity	Disease	D064420
+17111419	1246	1253	calcium	Chemical	D002118
+17111419	CID	C102006	D006996
+
+17175308|t|Proteinuria after conversion to sirolimus in renal transplant recipients.
+17175308|a|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.
+17175308	0	11	Proteinuria	Disease	D011507
+17175308	32	41	sirolimus	Chemical	D020123
+17175308	74	83	Sirolimus	Chemical	D020123
+17175308	85	88	SRL	Chemical	D020123
+17175308	147	158	proteinuria	Disease	D011507
+17175308	197	206	sirolimus	Chemical	D020123
+17175308	371	382	proteinuria	Disease	D011507
+17175308	389	392	SRL	Chemical	D020123
+17175308	460	463	SRL	Chemical	D020123
+17175308	494	523	chronic allograft nephropathy	Disease	D051436
+17175308	525	528	CAN	Disease	D007674
+17175308	539	548	neoplasia	Disease	D009369
+17175308	558	574	Kaposi's sarcoma	Disease	D012514
+17175308	581	593	skin cancers	Disease	D012878
+17175308	599	616	intestinal tumors	Disease	D007414
+17175308	622	641	renal cell carsinom	Disease	D002292
+17175308	655	666	nephropathy	Disease	D007674
+17175308	676	679	SRL	Chemical	D020123
+17175308	775	778	SRL	Chemical	D020123
+17175308	819	830	Proteinuria	Disease	D011507
+17175308	981	992	proteinuria	Disease	D011507
+17175308	1030	1041	proteinuria	Disease	D011507
+17175308	1062	1073	proteinuria	Disease	D011507
+17175308	1224	1235	proteinuria	Disease	D011507
+17175308	1243	1252	nephrotic	Disease	D009404
+17175308	1335	1371	membranoproliferative glomerulopathy	Disease	D015433
+17175308	1376	1398	interstitial nephritis	Disease	D009395
+17175308	1462	1472	creatinine	Chemical	D003404
+17175308	1536	1539	SRL	Chemical	D020123
+17175308	1685	1688	CAN	Disease	D007674
+17175308	1693	1709	Kaposi's sarcoma	Disease	D012514
+17175308	1863	1873	creatinine	Chemical	D003404
+17175308	1957	1968	proteinuria	Disease	D011507
+17175308	1997	2000	SRL	Chemical	D020123
+17175308	2134	2137	CAN	Disease	D007674
+17175308	2142	2153	proteinuria	Disease	D011507
+17175308	2209	2212	SRL	Chemical	D020123
+17175308	CID	D020123	D011507
+
+17244258|t|In vitro characterization of parasympathetic and sympathetic responses in cyclophosphamide-induced cystitis in the rat.
+17244258|a|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.
+17244258	74	90	cyclophosphamide	Chemical	D003520
+17244258	99	107	cystitis	Disease	D003556
+17244258	123	139	cyclophosphamide	Chemical	D003520
+17244258	148	156	cystitis	Disease	D003556
+17244258	323	331	cystitis	Disease	D003556
+17244258	417	433	cyclophosphamide	Chemical	D003520
+17244258	614	622	atropine	Chemical	D001285
+17244258	830	876	alpha,beta-methylene adenosine-5'-triphosphate	Chemical	C002630
+17244258	878	894	alpha,beta-meATP	Chemical	C002630
+17244258	987	995	atropine	Chemical	D001285
+17244258	997	1033	4-diphenylacetoxy-N-methylpiperidine	Chemical	C042375
+17244258	1035	1041	4-DAMP	Chemical	C042375
+17244258	1073	1086	methoctramine	Chemical	C054938
+17244258	1110	1121	pirenzepine	Chemical	D010890
+17244258	1278	1284	4-DAMP	Chemical	C042375
+17244258	1349	1362	methoctramine	Chemical	C054938
+17244258	1367	1378	pirenzepine	Chemical	D010890
+17244258	1542	1553	pirenzepine	Chemical	D010890
+17244258	1558	1564	4-DAMP	Chemical	C042375
+17244258	1666	1679	methoctramine	Chemical	C054938
+17244258	1780	1789	carbachol	Chemical	D002217
+17244258	1794	1797	ATP	Chemical	D000255
+17244258	1874	1883	potassium	Chemical	D011188
+17244258	1894	1906	isoprenaline	Chemical	D007545
+17244258	1969	1977	cystitis	Disease	D003556
+17244258	CID	D003520	D003556
+
+18020536|t|Associations between use of benzodiazepines or related drugs and health, physical abilities and cognitive function: a non-randomised clinical study in the elderly.
+18020536|a|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.
+18020536	28	43	benzodiazepines	Chemical	D001569
+18020536	219	234	benzodiazepines	Chemical	D001569
+18020536	253	257	BZDs	Chemical	D001569
+18020536	583	587	BZDs	Chemical	D001569
+18020536	907	911	BZDs	Chemical	D001569
+18020536	1205	1213	oxazepam	Chemical	D010076
+18020536	1215	1224	temazepam	Chemical	D013693
+18020536	1229	1238	zopiclone	Chemical	C515050
+18020536	1347	1351	BZDs	Chemical	D001569
+18020536	1568	1576	dementia	Disease	D003704
+18020536	1638	1642	BZDs	Chemical	D001569
+18020536	1731	1735	BZDs	Chemical	D001569
+18020536	1760	1769	dizziness	Disease	D004244
+18020536	1771	1789	inability to sleep	Disease	D007319
+18020536	1817	1826	tiredness	Disease	D005221
+18020536	1896	1915	depressive symptoms	Disease	D003866
+18020536	1971	1975	BZDs	Chemical	D001569
+18020536	2141	2150	temazepam	Chemical	D013693
+18020536	CID	D001569	D005221
+18020536	CID	D001569	D003866
+18020536	CID	D001569	D007319
+18020536	CID	D001569	D004244
+
+18023325|t|Acute vocal fold palsy after acute disulfiram intoxication.
+18023325|a|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.
+18023325	6	22	vocal fold palsy	Disease	D014826
+18023325	35	45	disulfiram	Chemical	D004221
+18023325	66	87	peripheral neuropathy	Disease	D010523
+18023325	100	110	disulfiram	Chemical	D004221
+18023325	111	119	overdose	Disease	D062787
+18023325	173	189	vocal fold palsy	Disease	D014826
+18023325	256	269	quadriparesis	Disease	D011782
+18023325	283	287	pain	Disease	D010146
+18023325	289	301	sensory loss	Disease	C580162
+18023325	307	318	paresthesia	Disease	D010292
+18023325	398	408	disulfiram	Chemical	D004221
+18023325	425	432	ALCOHOL	Chemical	D000431
+18023325	621	627	ataxia	Disease	D001259
+18023325	632	641	giddiness	Disease	D004244
+18023325	655	665	hoarseness	Disease	D006685
+18023325	834	848	polyneuropathy	Disease	D011115
+18023325	1126	1131	palsy	Disease	D010243
+18023325	1215	1229	polyneuropathy	Disease	D011115
+18023325	1250	1260	disulfiram	Chemical	D004221
+18023325	CID	D004221	D010292
+18023325	CID	D004221	D011782
+18023325	CID	D004221	D010146
+18023325	CID	D004221	D010523
+18023325	CID	D004221	D001259
+18023325	CID	D004221	D014826
+
+18208574|t|Higher optical density of an antigen assay predicts thrombosis in patients with heparin-induced thrombocytopenia.
+18208574|a|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.
+18208574	52	62	thrombosis	Disease	D013927
+18208574	80	87	heparin	Chemical	D006493
+18208574	96	112	thrombocytopenia	Disease	D013921
+18208574	192	199	heparin	Chemical	D006493
+18208574	208	224	thrombocytopenia	Disease	D013921
+18208574	226	229	HIT	Disease	D013921
+18208574	250	260	thrombosis	Disease	D013927
+18208574	327	334	heparin	Chemical	D006493
+18208574	430	446	thrombocytopenia	Disease	D013921
+18208574	482	489	heparin	Chemical	D006493
+18208574	606	613	heparin	Chemical	D006493
+18208574	664	667	HIT	Disease	D013921
+18208574	681	691	thrombosis	Disease	D013927
+18208574	725	728	HIT	Disease	D013921
+18208574	737	747	thrombosis	Disease	D013927
+18208574	771	774	HIT	Disease	D013921
+18208574	794	804	thrombosis	Disease	D013927
+18208574	860	870	thrombosis	Disease	D013927
+18208574	945	948	HIT	Disease	D013921
+18208574	963	973	thrombosis	Disease	D013927
+18208574	998	1001	HIT	Disease	D013921
+18208574	1061	1071	thrombosis	Disease	D013927
+18208574	1116	1119	HIT	Disease	D013921
+18208574	1149	1159	thrombosis	Disease	D013927
+18208574	1219	1222	HIT	Disease	D013921
+18208574	1252	1262	thrombosis	Disease	D013927
+18208574	1386	1389	HIT	Disease	D013921
+18208574	1444	1454	thrombosis	Disease	D013927
+18208574	1598	1608	thrombosis	Disease	D013927
+18208574	1632	1642	thrombotic	Disease	D013927
+18208574	1754	1764	thrombosis	Disease	D013927
+18208574	1791	1794	HIT	Disease	D013921
+18208574	CID	D006493	D013927
+18208574	CID	D006493	D013921
+
+18343374|t|Central retinal vein occlusion associated with clomiphene-induced ovulation.
+18343374|a|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.
+18343374	8	30	retinal vein occlusion	Disease	D012170
+18343374	47	57	clomiphene	Chemical	D002996
+18343374	116	138	retinal vein occlusion	Disease	D012170
+18343374	155	173	clomiphene citrate	Chemical	D002996
+18343374	175	177	CC	Chemical	D002996
+18343374	305	316	infertility	Disease	D007247
+18343374	328	342	blurred vision	Disease	D014786
+18343374	390	392	CC	Chemical	D002996
+18343374	435	457	retinal vein occlusion	Disease	D012170
+18343374	489	491	CC	Chemical	D002996
+18343374	550	572	retinal vein occlusion	Disease	D012170
+18343374	596	598	CC	Chemical	D002996
+18343374	634	648	thromboembolic	Disease	D013923
+18343374	666	668	CC	Chemical	D002996
+18343374	737	755	visual disturbance	Disease	D014786
+18343374	762	764	CC	Chemical	D002996
+18343374	847	869	retinal vein occlusion	Disease	D012170
+18343374	891	893	CC	Chemical	D002996
+18343374	934	945	infertility	Disease	D007247
+18343374	960	962	CC	Chemical	D002996
+18343374	CID	D002996	D012170
+18343374	CID	D002996	D014786
+
+18417364|t|Nicotine-induced nystagmus correlates with midpontine activation.
+18417364|a|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.
+18417364	0	8	Nicotine	Chemical	D009538
+18417364	17	26	nystagmus	Disease	D009759
+18417364	88	96	nicotine	Chemical	D009538
+18417364	105	114	nystagmus	Disease	D009759
+18417364	116	119	NIN	Disease	D009759
+18417364	210	213	NIN	Disease	D009759
+18417364	259	267	nicotine	Chemical	D009538
+18417364	401	404	NIN	Disease	D009759
+18417364	427	433	oxygen	Chemical	D010100
+18417364	525	528	NIN	Disease	D009759
+18417364	CID	D009538	D009759
+
+18442015|t|Protective effect of verapamil on gastric hemorrhagic ulcers in severe atherosclerotic rats.
+18442015|a|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.
+18442015	21	30	verapamil	Chemical	D014700
+18442015	34	53	gastric hemorrhagic	Disease	D006471
+18442015	54	60	ulcers	Disease	D014456
+18442015	71	86	atherosclerotic	Disease	D050197
+18442015	133	151	gastric hemorrhage	Disease	D006471
+18442015	187	202	atherosclerotic	Disease	D050197
+18442015	308	317	histamine	Chemical	D006632
+18442015	412	430	gastric hemorrhage	Disease	D006471
+18442015	435	440	ulcer	Disease	D014456
+18442015	454	469	atherosclerosis	Disease	D050197
+18442015	501	511	vitamin D2	Chemical	D004872
+18442015	516	527	cholesterol	Chemical	D002784
+18442015	568	577	verapamil	Chemical	D014700
+18442015	586	591	ulcer	Disease	D014456
+18442015	723	733	vitamin D2	Chemical	D004872
+18442015	738	749	cholesterol	Chemical	D002784
+18442015	760	775	atherosclerosis	Disease	D050197
+18442015	980	989	histamine	Chemical	D006632
+18442015	1033	1040	luminal	Chemical	D010634
+18442015	1064	1069	ulcer	Disease	D014456
+18442015	1102	1117	atherosclerotic	Disease	D050197
+18442015	1144	1151	calcium	Chemical	D002118
+18442015	1159	1170	cholesterol	Chemical	D002784
+18442015	1230	1245	atherosclerotic	Disease	D050197
+18442015	1267	1273	ulcers	Disease	D014456
+18442015	1361	1370	histamine	Chemical	D006632
+18442015	1399	1406	luminal	Chemical	D010634
+18442015	1496	1505	histamine	Chemical	D006632
+18442015	1509	1527	gastric hemorrhage	Disease	D006471
+18442015	1535	1540	ulcer	Disease	D014456
+18442015	1560	1575	atherosclerotic	Disease	D050197
+18442015	1587	1598	hemorrhagic	Disease	D006471
+18442015	1599	1604	ulcer	Disease	D014456
+18442015	1696	1705	verapamil	Chemical	D014700
+18442015	1707	1722	Atherosclerosis	Disease	D050197
+18442015	1737	1756	gastric hemorrhagic	Disease	D006471
+18442015	1757	1762	ulcer	Disease	D014456
+18442015	1827	1836	histamine	Chemical	D006632
+18442015	1905	1914	verapamil	Chemical	D014700
+18442015	CID	D004872	D006471
+18442015	CID	D004872	D050197
+18442015	CID	D002784	D006471
+18442015	CID	D002784	D014456
+18442015	CID	D002784	D050197
+18442015	CID	D004872	D014456
+
+18619688|t|Adriamycin-induced autophagic cardiomyocyte death plays a pathogenic role in a rat model of heart failure.
+18619688|a|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.
+18619688	0	10	Adriamycin	Chemical	D004317
+18619688	44	49	death	Disease	D003643
+18619688	92	105	heart failure	Disease	D006333
+18619688	145	158	heart failure	Disease	D006333
+18619688	170	180	adriamycin	Chemical	D004317
+18619688	315	328	heart failure	Disease	D006333
+18619688	340	350	adriamycin	Chemical	D004317
+18619688	406	419	heart failure	Disease	D006333
+18619688	430	445	3-methyladenine	Chemical	C025946
+18619688	447	450	3MA	Chemical	C025946
+18619688	501	514	heart failure	Disease	D006333
+18619688	540	550	adriamycin	Chemical	D004317
+18619688	660	670	adriamycin	Chemical	D004317
+18619688	692	695	3MA	Chemical	C025946
+18619688	701	711	adriamycin	Chemical	D004317
+18619688	842	843	K	Chemical	D011188
+18619688	1146	1149	3MA	Chemical	C025946
+18619688	1237	1247	adriamycin	Chemical	D004317
+18619688	1298	1301	3MA	Chemical	C025946
+18619688	1355	1365	adriamycin	Chemical	D004317
+18619688	1477	1482	death	Disease	D003643
+18619688	1530	1543	heart failure	Disease	D006333
+18619688	1563	1573	adriamycin	Chemical	D004317
+18619688	1634	1647	heart failure	Disease	D006333
+18619688	1658	1668	adriamycin	Chemical	D004317
+18619688	CID	D004317	D006333
+
+19308880|t|Confusion, a rather serious adverse drug reaction with valproic acid: a review of the French Pharmacovigilance database.
+19308880|a|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.
+19308880	0	9	Confusion	Disease	D003221
+19308880	55	68	valproic acid	Chemical	D014635
+19308880	135	144	Confusion	Disease	D003221
+19308880	198	211	valproic acid	Chemical	D014635
+19308880	513	522	confusion	Disease	D003221
+19308880	548	561	valproic acid	Chemical	D014635
+19308880	585	594	confusion	Disease	D003221
+19308880	614	627	valproic acid	Chemical	D014635
+19308880	652	661	Confusion	Disease	D003221
+19308880	715	728	valproic acid	Chemical	D014635
+19308880	978	987	confusion	Disease	D003221
+19308880	993	1006	valproic acid	Chemical	D014635
+19308880	CID	D014635	D003221
+
+19631624|t|Learning and memory deficits in ecstasy users and their neural correlates during a face-learning task.
+19631624|a|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.
+19631624	0	28	Learning and memory deficits	Disease	D007859|D008569	Learning deficits|memory deficits
+19631624	32	39	ecstasy	Chemical	D018817
+19631624	139	146	ecstasy	Chemical	D018817
+19631624	161	195	impairments in learning and memory	Disease	D007859|D008569	impairments in learning|impairments in memory
+19631624	251	258	ecstasy	Chemical	D018817
+19631624	616	623	ecstasy	Chemical	D018817
+19631624	693	701	cannabis	Chemical	D002188
+19631624	713	720	ecstasy	Chemical	D018817
+19631624	782	790	cannabis	Chemical	D002188
+19631624	854	885	Deficits in learning and memory	Disease	D007859|D008569	Deficits in learning|Deficits in memory
+19631624	903	916	hyperactivity	Disease	D006948
+19631624	952	960	cannabis	Chemical	D002188
+19631624	995	1002	Ecstasy	Chemical	D018817
+19631624	1087	1095	cannabis	Chemical	D002188
+19631624	1179	1186	ecstasy	Chemical	D018817
+19631624	1196	1209	hyperactivity	Disease	D006948
+19631624	1330	1337	Ecstasy	Chemical	D018817
+19631624	1471	1478	ecstasy	Chemical	D018817
+19631624	1483	1491	cannabis	Chemical	D002188
+19631624	1665	1672	ecstasy	Chemical	D018817
+19631624	1733	1741	cannabis	Chemical	D002188
+19631624	1753	1760	ecstasy	Chemical	D018817
+19631624	1861	1871	neurotoxic	Disease	D020258
+19631624	1883	1890	ecstasy	Chemical	D018817
+19631624	CID	D018817	D008569
+19631624	CID	D018817	D007859
+
+20003049|t|Prolonged elevation of plasma argatroban in a cardiac transplant patient with a suspected history of heparin-induced thrombocytopenia with thrombosis.
+20003049|a|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.
+20003049	30	40	argatroban	Chemical	C031942
+20003049	101	108	heparin	Chemical	D006493
+20003049	117	133	thrombocytopenia	Disease	D013921
+20003049	139	149	thrombosis	Disease	D013927
+20003049	277	284	heparin	Chemical	D006493
+20003049	293	309	thrombocytopenia	Disease	D013921
+20003049	311	314	HIT	Disease	D013921
+20003049	319	322	HIT	Disease	D013921
+20003049	328	338	thrombosis	Disease	D013927
+20003049	340	344	HITT	Disease	D013921|D013927
+20003049	426	440	critically ill	Disease	D016638
+20003049	477	481	HITT	Disease	D013921|D013927
+20003049	499	509	argatroban	Chemical	C031942
+20003049	789	830	intraoperative and postoperative bleeding	Disease	D016063|D019106	intraoperative bleeding|postoperative bleeding
+20003049	933	943	argatroban	Chemical	C031942
+20003049	1054	1064	argatroban	Chemical	C031942
+20003049	1144	1154	argatroban	Chemical	C031942
+20003049	1274	1292	hepatic impairment	Disease	D008107
+20003049	1331	1341	argatroban	Chemical	C031942
+20003049	1468	1478	argatroban	Chemical	C031942
+20003049	1526	1538	coagulopathy	Disease	D001778
+20003049	1776	1786	argatroban	Chemical	C031942
+20003049	1836	1848	coagulopathy	Disease	D001778
+20003049	CID	C031942	D016063
+20003049	CID	C031942	D019106
+
+20196116|t|Antituberculosis therapy-induced acute liver failure: magnitude, profile, prognosis, and predictors of outcome.
+20196116|a|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.
+20196116	0	16	Antituberculosis	Chemical	D000995
+20196116	33	52	acute liver failure	Disease	D017114
+20196116	112	128	Antituberculosis	Chemical	D000995
+20196116	154	173	acute liver failure	Disease	D017114
+20196116	179	182	ALF	Disease	D017114
+20196116	214	217	ALF	Disease	D017114
+20196116	260	263	ALF	Disease	D017114
+20196116	390	393	ALF	Disease	D017114
+20196116	447	450	ALF	Disease	D017114
+20196116	566	591	hepatitis virus infection	Disease	D006525
+20196116	679	691	tuberculosis	Disease	D014376
+20196116	697	700	ALF	Disease	D017114
+20196116	826	833	icterus	Disease	D007565
+20196116	834	848	encephalopathy	Disease	D001927
+20196116	913	916	ALF	Disease	D017114
+20196116	964	978	encephalopathy	Disease	D001927
+20196116	983	997	cerebral edema	Disease	D001929
+20196116	1062	1084	Gastrointestinal bleed	Disease	D006471
+20196116	1086	1094	seizures	Disease	D012640
+20196116	1096	1105	infection	Disease	D007239
+20196116	1111	1130	acute renal failure	Disease	D058186
+20196116	1242	1253	hepatitis E	Disease	D016751
+20196116	1290	1293	ALF	Disease	D017114
+20196116	1299	1302	ALF	Disease	D017114
+20196116	1446	1449	ALF	Disease	D017114
+20196116	1620	1629	bilirubin	Chemical	D001663
+20196116	1718	1732	encephalopathy	Disease	D001927
+20196116	1766	1769	ALF	Disease	D017114
+20196116	1790	1793	ALF	Disease	D017114
+20196116	CID	D000995	D017114
+
+20470218|t|Central nervous system complications during treatment of acute lymphoblastic leukemia in a single pediatric institution.
+20470218|a|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.
+20470218	0	36	Central nervous system complications	Disease	D002493
+20470218	57	85	acute lymphoblastic leukemia	Disease	D054198
+20470218	121	163	Central nervous system (CNS) complications	Disease	D002493
+20470218	194	222	acute lymphoblastic leukemia	Disease	D054198
+20470218	224	227	ALL	Disease	D054198
+20470218	432	458	neurological complications	Disease	D002493
+20470218	466	469	ALL	Disease	D054198
+20470218	618	639	leukemic infiltration	Disease	D017254
+20470218	670	691	peripheral neuropathy	Disease	D010523
+20470218	704	718	encephalopathy	Disease	D001927
+20470218	733	755	neurocognitive defects	Disease	D002493
+20470218	894	897	ALL	Disease	D054198
+20470218	967	986	leukoencephalopathy	Disease	D056784
+20470218	1006	1012	stroke	Disease	D020521
+20470218	1022	1044	temporal lobe epilepsy	Disease	D004833
+20470218	1064	1076	methotrexate	Chemical	D008727
+20470218	1077	1085	toxicity	Disease	D064420
+20470218	1107	1151	inappropriate antidiuretic hormone secretion	Disease	D007177
+20470218	1260	1263	ALL	Disease	D054198
+20470218	CID	D008727	D002493
+
+20722491|t|Safety of capecitabine: a review.
+20722491|a|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.
+20722491	10	22	capecitabine	Chemical	C110904
+20722491	59	76	Fluoropyrimidines	Chemical	-1
+20722491	92	106	5-fluorouracil	Chemical	D005472
+20722491	108	112	5-FU	Chemical	D005472
+20722491	169	175	tumors	Disease	D009369
+20722491	187	231	colorectal, breast and head and neck cancers	Disease	D015179|D001943|D006258	colorectal cancers|breast cancers|head and neck cancers
+20722491	333	345	capecitabine	Chemical	C110904
+20722491	467	479	capecitabine	Chemical	C110904
+20722491	539	563	renal and kidney disease	Disease	D007674
+20722491	615	627	capecitabine	Chemical	C110904
+20722491	663	675	Capecitabine	Chemical	C110904
+20722491	698	702	5-FU	Chemical	D005472
+20722491	913	998	colorectal, breast, pancreaticobiliary, gastric, renal cell and head and neck cancers	Disease	D015179|D001943|D010190|D013274|D002292|D006258	colorectal cancers|breast cancers|pancreaticobiliary cancers|gastric cancers|renal cell cancers|head and neck cancers
+20722491	1044	1056	capecitabine	Chemical	C110904
+20722491	1061	1069	diarrhea	Disease	D003967
+20722491	1071	1077	nausea	Disease	D009325
+20722491	1079	1087	vomiting	Disease	D014839
+20722491	1089	1099	stomatitis	Disease	D013280
+20722491	1104	1122	hand-foot syndrome	Disease	D060831
+20722491	1124	1136	Capecitabine	Chemical	C110904
+20722491	1230	1260	hepatic and renal dysfunctions	Disease	D008107|D007674	hepatic dysfunctions|renal dysfunctions
+20722491	CID	C110904	D060831
+20722491	CID	C110904	D013280
+20722491	CID	C110904	D014839
+20722491	CID	C110904	D003967
+20722491	CID	C110904	D009325
+
+20882060|t|Effects of pallidal neurotensin on haloperidol-induced parkinsonian catalepsy: behavioral and electrophysiological studies.
+20882060|a|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.
+20882060	20	31	neurotensin	Chemical	D009496
+20882060	35	46	haloperidol	Chemical	D006220
+20882060	55	77	parkinsonian catalepsy	Disease	D002375
+20882060	348	359	neurotensin	Chemical	D009496
+20882060	470	481	neurotensin	Chemical	D009496
+20882060	485	496	haloperidol	Chemical	D006220
+20882060	505	526	parkinsonian symptoms	Disease	D010302
+20882060	665	676	neurotensin	Chemical	D009496
+20882060	711	722	haloperidol	Chemical	D006220
+20882060	731	753	parkinsonian catalepsy	Disease	D002375
+20882060	825	836	neurotensin	Chemical	D009496
+20882060	904	915	haloperidol	Chemical	D006220
+20882060	936	974	neurotensin type-1 receptor antagonist	Chemical	C079087
+20882060	975	982	SR48692	Chemical	C079087
+20882060	1059	1070	neurotensin	Chemical	D009496
+20882060	1107	1118	neurotensin	Chemical	D009496
+20882060	1148	1159	neurotensin	Chemical	D009496
+20882060	CID	D006220	D002375
+
+26094|t|Antihypertensive drugs and depression: a reappraisal.
+26094|a|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.
+26094	27	37	depression	Disease	D003866
+26094	79	91	hypertensive	Disease	D006973
+26094	129	141	hypertensive	Disease	D006973
+26094	287	297	depression	Disease	D003866
+26094	355	367	hypertensive	Disease	D006973
+26094	375	387	Hypertensive	Disease	D006973
+26094	402	413	psychiatric	Disease	D001523
+26094	451	461	depression	Disease	D003866
+26094	542	553	depressions	Disease	D003866
+26094	567	578	methyl dopa	Chemical	D008750
+26094	601	612	psychiatric	Disease	D001523
+26094	CID	D008750	D003866
+
+322550|t|Pulmonary shunt and cardiovascular responses to CPAP during nitroprusside-induced hypotension.
+322550|a|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.
+322550	60	73	nitroprusside	Chemical	D009599
+322550	82	93	hypotension	Disease	D007022
+322550	255	275	sodium nitroprusside	Chemical	D009599
+322550	352	365	nitroprusside	Chemical	D009599
+322550	381	384	H2O	Chemical	D014867
+322550	564	567	H2O	Chemical	D014867
+322550	580	593	nitroprusside	Chemical	D009599
+322550	622	657	decrease in arterial blood pressure	Disease	D007022
+322550	701	725	decreased cardiac output	Disease	D002303
+322550	737	750	Nitroprusside	Chemical	D009599
+322550	770	806	decreases in arterial blood pressure	Disease	D007022
+322550	921	924	H2O	Chemical	D014867
+322550	937	950	nitroprusside	Chemical	D009599
+322550	1026	1029	H2O	Chemical	D014867
+322550	1122	1135	nitroprusside	Chemical	D009599
+322550	1258	1271	nitroprusside	Chemical	D009599
+322550	1378	1381	H2O	Chemical	D014867
+322550	1423	1478	decreases in arterial blood pressure and cardiac output	Disease	D007022|D002303	decreases in arterial blood pressure|decreases in cardiac output
+322550	CID	D009599	D007022
+
+869641|t|Mediation of enhanced reflex vagal bradycardia by L-dopa via central dopamine formation in dogs.
+869641|a|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.
+869641	35	46	bradycardia	Disease	D001919
+869641	50	56	L-dopa	Chemical	D007980
+869641	69	77	dopamine	Chemical	D004298
+869641	97	103	L-Dopa	Chemical	D007980
+869641	209	215	MK-486	Chemical	D002230
+869641	247	250	MAO	Chemical	D008995
+869641	287	298	bradycardia	Disease	D001919
+869641	318	332	norepinephrine	Chemical	D009638
+869641	363	369	L-dopa	Chemical	D007980
+869641	371	401	DL-Threo-dihydroxyphenylserine	Chemical	D015103
+869641	469	483	norepinephrine	Chemical	D009638
+869641	485	491	FLA-63	Chemical	D005406
+869641	495	503	dopamine	Chemical	D004298
+869641	559	570	hypotension	Disease	D007022
+869641	572	583	bradycardia	Disease	D001919
+869641	614	620	L-dopa	Chemical	D007980
+869641	622	630	Pimozide	Chemical	D010868
+869641	661	667	L-dopa	Chemical	D007980
+869641	884	898	norepinephrine	Chemical	D009638
+869641	909	915	L-dopa	Chemical	D007980
+869641	929	940	bradycardia	Disease	D001919
+869641	951	965	norepinephrine	Chemical	D009638
+869641	1023	1028	5-HTP	Chemical	D006916
+869641	1109	1120	bradycardia	Disease	D001919
+869641	1124	1138	norepinephrine	Chemical	D009638
+869641	1161	1167	L-dopa	Chemical	D007980
+869641	1184	1195	bradycardia	Disease	D001919
+869641	1286	1294	dopamine	Chemical	D004298
+869641	1307	1321	norepinephrine	Chemical	D009638
+869641	CID	D009638	D001919
+
+1749407|t|Cocaine-induced myocardial infarction: clinical observations and pathogenetic considerations.
+1749407|a|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.
+1749407	0	7	Cocaine	Chemical	D003042
+1749407	16	37	myocardial infarction	Disease	D009203
+1749407	188	195	cocaine	Chemical	D003042
+1749407	210	237	acute myocardial infarction	Disease	D009203
+1749407	312	339	acute myocardial infarction	Disease	D009203
+1749407	382	388	oxygen	Chemical	D010100
+1749407	412	419	cocaine	Chemical	D003042
+1749407	503	530	atherosclerotic obstruction	Disease	D050197
+1749407	532	550	coronary occlusion	Disease	D054059
+1749407	565	570	spasm	Disease	D013035
+1749407	572	580	thrombus	Disease	D013927
+1749407	606	611	spasm	Disease	D013035
+1749407	680	687	cocaine	Chemical	D003042
+1749407	814	819	spasm	Disease	D013035
+1749407	1004	1014	infarction	Disease	D007238
+1749407	1149	1156	cocaine	Chemical	D003042
+1749407	1438	1448	thrombotic	Disease	D013927
+1749407	1459	1466	cocaine	Chemical	D003042
+1749407	CID	D003042	D009203
+
+1786266|t|Rabbit syndrome, antidepressant use, and cerebral perfusion SPECT scan findings.
+1786266|a|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.
+1786266	0	15	Rabbit syndrome	Disease	D001480
+1786266	17	31	antidepressant	Chemical	D000928
+1786266	85	100	rabbit syndrome	Disease	D001480
+1786266	226	236	imipramine	Chemical	D007099
+1786266	325	340	antidepressants	Chemical	D000928
+1786266	391	424	decreased basal ganglia perfusion	Disease	D001480
+1786266	435	452	movement disorder	Disease	D009069
+1786266	508	523	rabbit syndrome	Disease	D001480
+1786266	CID	D007099	D001480
+
+1835291|t|Acute bronchodilating effects of ipratropium bromide and theophylline in chronic obstructive pulmonary disease.
+1835291|a|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.
+1835291	33	52	ipratropium bromide	Chemical	D009241
+1835291	57	69	theophylline	Chemical	D013806
+1835291	73	110	chronic obstructive pulmonary disease	Disease	D029424
+1835291	159	178	ipratropium bromide	Chemical	D009241
+1835291	220	232	theophylline	Chemical	D013806
+1835291	400	437	chronic obstructive pulmonary disease	Disease	D029424
+1835291	643	654	ipratropium	Chemical	D009241
+1835291	690	702	theophylline	Chemical	D013806
+1835291	781	792	ipratropium	Chemical	D009241
+1835291	804	816	theophylline	Chemical	D013806
+1835291	865	876	ipratropium	Chemical	D009241
+1835291	896	908	theophylline	Chemical	D013806
+1835291	964	976	theophylline	Chemical	D013806
+1835291	997	1040	cardiovascular and gastrointestinal systems	Disease	D002318|D005767	cardiovascular systems|gastrointestinal systems
+1835291	1066	1077	ipratropium	Chemical	D009241
+1835291	1120	1132	theophylline	Chemical	D013806
+1835291	1150	1177	chronic airflow obstruction	Disease	D029424
+1835291	CID	D013806	D002318
+1835291	CID	D013806	D005767
+
+1919871|t|Irreversible damage to the medullary interstitium in experimental analgesic nephropathy in F344 rats.
+1919871|a|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.
+1919871	76	87	nephropathy	Disease	D007674
+1919871	102	126	Renal papillary necrosis	Disease	D007681
+1919871	128	131	RPN	Disease	D007681
+1919871	232	239	aspirin	Chemical	D001241
+1919871	244	255	paracetamol	Chemical	D000082
+1919871	1248	1251	RPN	Disease	D007681
+1919871	CID	D000082	D007681
+1919871	CID	D001241	D007681
+
+1987816|t|Less frequent lithium administration and lower urine volume.
+1987816|a|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.
+1987816	14	21	lithium	Chemical	D008094
+1987816	153	160	lithium	Chemical	D008094
+1987816	327	334	lithium	Chemical	D008094
+1987816	439	446	lithium	Chemical	D008094
+1987816	454	464	creatinine	Chemical	D003404
+1987816	547	554	lithium	Chemical	D008094
+1987816	631	638	lithium	Chemical	D008094
+1987816	668	675	lithium	Chemical	D008094
+1987816	713	723	creatinine	Chemical	D003404
+1987816	786	793	lithium	Chemical	D008094
+1987816	846	853	Lithium	Chemical	D008094
+1987816	862	870	polyuria	Disease	D011141
+1987816	CID	D008094	D011141
+
+2054792|t|Effect of adriamycin combined with whole body hyperthermia on tumor and normal tissues.
+2054792|a|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.
+2054792	10	20	adriamycin	Chemical	D004317
+2054792	46	58	hyperthermia	Disease	D005334
+2054792	62	67	tumor	Disease	D009369
+2054792	111	121	Adriamycin	Chemical	D004317
+2054792	168	178	toxicities	Disease	D064420
+2054792	193	205	hyperthermia	Disease	D005334
+2054792	283	288	tumor	Disease	D009369
+2054792	329	339	toxicities	Disease	D064420
+2054792	347	357	leukopenia	Disease	D007970
+2054792	362	378	thrombocytopenia	Disease	D013921
+2054792	403	413	toxicities	Disease	D064420
+2054792	421	449	myocardial and kidney injury	Disease	D006331|D007674	myocardial injury|kidney injury
+2054792	545	557	hyperthermia	Disease	D005334
+2054792	600	610	Adriamycin	Chemical	D004317
+2054792	883	908	cardiac and renal lesions	Disease	D006331|D007674	cardiac lesions|renal lesions
+2054792	961	973	hyperthermia	Disease	D005334
+2054792	983	993	Adriamycin	Chemical	D004317
+2054792	1035	1043	toxicity	Disease	D064420
+2054792	CID	D004317	D006331
+
+2304736|t|Prazosin-induced stress incontinence.
+2304736|a|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.
+2304736	0	8	Prazosin	Chemical	D011224
+2304736	17	36	stress incontinence	Disease	D014550
+2304736	56	75	stress incontinence	Disease	D014550
+2304736	83	91	prazosin	Chemical	D011224
+2304736	139	147	Prazosin	Chemical	D011224
+2304736	480	488	prazosin	Chemical	D011224
+2304736	525	534	verapamil	Chemical	D014700
+2304736	540	552	incontinence	Disease	D014549
+2304736	784	803	stress incontinence	Disease	D014550
+2304736	817	825	prazosin	Chemical	D011224
+2304736	916	928	incontinence	Disease	D014549
+2304736	CID	D011224	D014550
+
+2312209|t|Myocardial infarction following sublingual administration of isosorbide dinitrate.
+2312209|a|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.
+2312209	0	21	Myocardial infarction	Disease	D009203
+2312209	61	81	isosorbide dinitrate	Chemical	D007548
+2312209	116	124	necrosis	Disease	D009336
+2312209	146	167	myocardial infarction	Disease	D009203
+2312209	221	241	isosorbide dinitrate	Chemical	D007548
+2312209	343	348	spasm	Disease	D013035
+2312209	353	364	hypotension	Disease	D007022
+2312209	374	393	myocardial ischemia	Disease	D017202
+2312209	430	456	coronary arterial stenosis	Disease	D023921
+2312209	483	511	acute coronary insufficiency	Disease	D054058
+2312209	CID	D007548	D009203
+
+2549018|t|Fluoxetine-induced akathisia: clinical and theoretical implications.
+2549018|a|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.
+2549018	0	10	Fluoxetine	Chemical	D005473
+2549018	19	28	akathisia	Disease	D017109
+2549018	93	103	fluoxetine	Chemical	D005473
+2549018	125	154	obsessive compulsive disorder	Disease	D009771
+2549018	158	174	major depression	Disease	D003865
+2549018	185	194	akathisia	Disease	D017109
+2549018	208	218	fluoxetine	Chemical	D005473
+2549018	325	332	anxiety	Disease	D001008
+2549018	390	399	akathisia	Disease	D017109
+2549018	456	465	akathisia	Disease	D017109
+2549018	508	518	fluoxetine	Chemical	D005473
+2549018	527	536	akathisia	Disease	D017109
+2549018	579	588	Akathisia	Disease	D017109
+2549018	628	638	fluoxetine	Chemical	D005473
+2549018	717	728	propranolol	Chemical	D011433
+2549018	780	790	fluoxetine	Chemical	D005473
+2549018	799	808	akathisia	Disease	D017109
+2549018	929	939	fluoxetine	Chemical	D005473
+2549018	948	957	akathisia	Disease	D017109
+2549018	972	986	antidepressant	Chemical	D000928
+2549018	CID	D005473	D017109
+
+2611118|t|Chronic active hepatitis associated with diclofenac sodium therapy.
+2611118|a|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.
+2611118	0	24	Chronic active hepatitis	Disease	D006521
+2611118	41	58	diclofenac sodium	Chemical	D004008
+2611118	68	85	Diclofenac sodium	Chemical	D004008
+2611118	87	95	Voltarol	Chemical	D004008
+2611118	171	188	phenylacetic acid	Chemical	C025136
+2611118	238	269	abnormalities of liver function	Disease	D056486
+2611118	316	325	hepatitis	Disease	D056486
+2611118	337	347	diclofenac	Chemical	D004008
+2611118	381	405	chronic active hepatitis	Disease	D006521
+2611118	436	453	diclofenac sodium	Chemical	D004008
+2611118	CID	D004008	D056486
+
+2673163|t|Stroke associated with cocaine use.
+2673163|a|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.
+2673163	0	6	Stroke	Disease	D020521
+2673163	23	30	cocaine	Chemical	D003042
+2673163	71	78	cocaine	Chemical	D003042
+2673163	98	104	stroke	Disease	D020521
+2673163	239	245	Stroke	Disease	D020521
+2673163	255	262	cocaine	Chemical	D003042
+2673163	333	355	Intracranial aneurysms	Disease	D002532
+2673163	359	386	arteriovenous malformations	Disease	D001165
+2673163	461	480	cerebral vasculitis	Disease	D020293
+2673163	510	529	Cerebral infarction	Disease	D002544
+2673163	561	585	intracerebral hemorrhage	Disease	D002543
+2673163	603	626	subarachnoid hemorrhage	Disease	D013345
+2673163	695	701	stroke	Disease	D020521
+2673163	713	720	cocaine	Chemical	D003042
+2673163	744	751	cocaine	Chemical	D003042
+2673163	763	769	stroke	Disease	D020521
+2673163	808	814	stroke	Disease	D020521
+2673163	839	846	cocaine	Chemical	D003042
+2673163	867	873	stroke	Disease	D020521
+2673163	880	887	cocaine	Chemical	D003042
+2673163	922	944	intracranial aneurysms	Disease	D002532
+2673163	949	976	arteriovenous malformations	Disease	D001165
+2673163	989	996	cocaine	Chemical	D003042
+2673163	1008	1014	stroke	Disease	D020521
+2673163	1033	1056	intracranial hemorrhage	Disease	D020300
+2673163	1073	1092	cerebral infarction	Disease	D002544
+2673163	CID	D003042	D002543
+2673163	CID	D003042	D013345
+2673163	CID	D003042	D002544
+
+3107448|t|Glyburide-induced hepatitis.
+3107448|a|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.
+3107448	0	9	Glyburide	Chemical	D005905
+3107448	18	27	hepatitis	Disease	D056486
+3107448	42	56	hepatotoxicity	Disease	D056486
+3107448	116	129	sulfonylureas	Chemical	D013453
+3107448	135	144	glyburide	Chemical	D005905
+3107448	166	178	sulfonylurea	Chemical	D013453
+3107448	206	220	hepatotoxicity	Disease	D056486
+3107448	246	271	type II diabetes mellitus	Disease	D003924
+3107448	285	314	acute hepatitis-like syndrome	Disease	D056486
+3107448	340	349	glyburide	Chemical	D005905
+3107448	394	409	viral infection	Disease	D014777
+3107448	481	503	drug-induced hepatitis	Disease	D056486
+3107448	552	561	glyburide	Chemical	D005905
+3107448	627	636	Glyburide	Chemical	D005905
+3107448	652	680	acute hepatitis-like illness	Disease	D056486
+3107448	CID	D005905	D056486
+
+3341566|t|Systolic pressure variation is greater during hemorrhage than during sodium nitroprusside-induced hypotension in ventilated dogs.
+3341566|a|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.
+3341566	46	56	hemorrhage	Disease	D006470
+3341566	69	89	sodium nitroprusside	Chemical	D009599
+3341566	98	109	hypotension	Disease	D007022
+3341566	349	360	hypotension	Disease	D007022
+3341566	436	446	hemorrhage	Disease	D006470
+3341566	448	451	HEM	Disease	D006470
+3341566	489	509	sodium nitroprusside	Chemical	D009599
+3341566	511	514	SNP	Chemical	D009599
+3341566	531	534	HEM	Disease	D006470
+3341566	543	554	hypotension	Disease	D007022
+3341566	664	667	SNP	Chemical	D009599
+3341566	924	935	hypotension	Disease	D007022
+3341566	966	969	HEM	Disease	D006470
+3341566	1016	1019	SNP	Chemical	D009599
+3341566	1176	1179	HEM	Disease	D006470
+3341566	1184	1187	SNP	Chemical	D009599
+3341566	1217	1228	hypotension	Disease	D007022
+3341566	1334	1345	hypotensive	Disease	D007022
+3341566	1439	1450	hypovolemia	Disease	D020896
+3341566	1474	1485	hypotension	Disease	D007022
+3341566	CID	D009599	D007022
+
+3564823|t|Drug-induced arterial spasm relieved by lidocaine. Case report.
+3564823|a|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.
+3564823	22	27	spasm	Disease	D013035
+3564823	40	49	lidocaine	Chemical	D008012
+3564823	123	139	sodium pentothal	Chemical	D013874
+3564823	178	196	cerebral ischaemia	Disease	D002545
+3564823	206	215	vasospasm	Disease	D020301
+3564823	232	240	gangrene	Disease	D005734
+3564823	346	355	lidocaine	Chemical	D008012
+3564823	442	451	vasospasm	Disease	D020301
+3564823	CID	D013874	D013035
+
+3676049|t|Cerebral blood flow and metabolism during isoflurane-induced hypotension in patients subjected to surgery for cerebral aneurysms.
+3676049|a|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.
+3676049	42	52	isoflurane	Chemical	D007530
+3676049	61	72	hypotension	Disease	D007022
+3676049	110	128	cerebral aneurysms	Disease	D002532
+3676049	182	188	oxygen	Chemical	D010100
+3676049	210	220	isoflurane	Chemical	D007530
+3676049	229	240	hypotension	Disease	D007022
+3676049	298	315	cerebral aneurysm	Disease	D002532
+3676049	371	395	subarachnoid haemorrhage	Disease	D013345
+3676049	460	465	xenon	Chemical	D014978
+3676049	519	529	isoflurane	Chemical	D007530
+3676049	563	576	nitrous oxide	Chemical	D009609
+3676049	580	586	oxygen	Chemical	D010100
+3676049	734	745	hypotension	Disease	D007022
+3676049	776	778	Hg	Chemical	D008628
+3676049	817	827	isoflurane	Chemical	D007530
+3676049	1025	1033	aneurysm	Disease	D000783
+3676049	1038	1048	isoflurane	Chemical	D007530
+3676049	1174	1185	hypotensive	Disease	D007022
+3676049	1273	1284	hypotension	Disease	D007022
+3676049	CID	D007530	D007022
+
+3719553|t|Allergic reaction to 5-fluorouracil infusion.
+3719553|a|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.
+3719553	0	17	Allergic reaction	Disease	D004342
+3719553	21	35	5-fluorouracil	Chemical	D005472
+3719553	49	66	allergic reaction	Disease	D004342
+3719553	81	100	angioneurotic edema	Disease	D000799
+3719553	134	148	5-fluorouracil	Chemical	D005472
+3719553	186	214	carcinoma of the oral cavity	Disease	D009062
+3719553	216	225	cirrhosis	Disease	D005355
+3719553	231	240	cisplatin	Chemical	D002945
+3719553	249	272	impaired renal function	Disease	D007674
+3719553	367	382	diphenhydramine	Chemical	D004155
+3719553	387	397	prednisone	Chemical	D011241
+3719553	451	468	allergic reaction	Disease	D004342
+3719553	CID	D005472	D000799
+
+4008111|t|Amiodarone-induced sinoatrial block.
+4008111|a|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.
+4008111	0	10	Amiodarone	Chemical	D000638
+4008111	19	35	sinoatrial block	Disease	D012848
+4008111	49	65	sinoatrial block	Disease	D012848
+4008111	81	91	amiodarone	Chemical	D000638
+4008111	132	154	primary cardiomyopathy	Disease	D009202
+4008111	156	186	Wolff-Parkinson-White syndrome	Disease	D014927
+4008111	191	219	supraventricular tachycardia	Disease	D013617
+4008111	248	258	amiodarone	Chemical	D000638
+4008111	296	312	sinoatrial block	Disease	D012848
+4008111	349	366	sinus bradycardia	Disease	D012804
+4008111	CID	D000638	D012848
+
+6133211|t|Possible teratogenicity of sulphasalazine.
+6133211|a|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.
+6133211	27	41	sulphasalazine	Chemical	D012460
+6133211	83	109	inflammatory bowel disease	Disease	D015212
+6133211	138	152	sulphasalazine	Chemical	D012460
+6133211	200	220	congenital anomalies	Disease	D000013
+6133211	265	283	ulcerative colitis	Disease	D003093
+6133211	313	337	coarctation of the aorta	Disease	D001017
+6133211	344	369	ventricular septal defect	Disease	D006345
+6133211	409	424	Crohn's disease	Disease	D003424
+6133211	463	496	Potter-type IIa polycystic kidney	Disease	D007690
+6133211	503	533	rudimentary left uterine cornu	Disease	-1
+6133211	581	596	Potter's facies	Disease	-1
+6133211	598	615	hypoplastic lungs	Disease	-1
+6133211	617	643	absent kidneys and ureters	Disease	-1
+6133211	649	668	talipes equinovarus	Disease	D003025
+6133211	724	738	sulphasalazine	Chemical	D012460
+6133211	CID	D012460	D003025
+6133211	CID	D012460	D001017
+6133211	CID	D012460	D006345
+6133211	CID	D012460	D007690
+
+6503301|t|Veno-occlusive liver disease after dacarbazine therapy (DTIC) for melanoma.
+6503301|a|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.
+6503301	0	28	Veno-occlusive liver disease	Disease	D006504
+6503301	35	46	dacarbazine	Chemical	D003606
+6503301	56	60	DTIC	Chemical	D003606
+6503301	66	74	melanoma	Disease	D008545
+6503301	86	121	veno-occlusive disease of the liver	Disease	D006504
+6503301	147	158	dacarbazine	Chemical	D003606
+6503301	160	164	DTIC	Chemical	D003606
+6503301	178	186	melanoma	Disease	D008545
+6503301	267	272	death	Disease	D003643
+6503301	331	348	venous congestion	Disease	D006940
+6503301	404	414	thrombosis	Disease	D013927
+6503301	CID	D003606	D006504
+
+6727060|t|A case of tardive dyskinesia caused by metoclopramide.
+6727060|a|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.
+6727060	10	28	tardive dyskinesia	Disease	D004409
+6727060	39	53	metoclopramide	Chemical	D008787
+6727060	55	85	Abnormal involuntary movements	Disease	D004409
+6727060	178	192	metoclopramide	Chemical	D008787
+6727060	197	222	gastrointestinal disorder	Disease	D005767
+6727060	343	357	metoclopramide	Chemical	D008787
+6727060	395	413	abnormal movements	Disease	D004409
+6727060	507	525	tardive dyskinesia	Disease	D004409
+6727060	CID	D008787	D004409
+
+7083920|t|Further observations on the electrophysiologic effects of oral amiodarone therapy.
+7083920|a|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.
+7083920	63	73	amiodarone	Chemical	D000638
+7083920	119	137	intra-Hisian block	Disease	D006327
+7083920	154	164	amiodarone	Chemical	D000638
+7083920	179	197	atrial tachycardia	Disease	D013617
+7083920	225	266	intraventricular conduction abnormalities	Disease	D006345
+7083920	300	318	atrial tachycardia	Disease	D013617
+7083920	441	451	amiodarone	Chemical	D000638
+7083920	500	514	atrial flutter	Disease	D001282
+7083920	559	569	Amiodarone	Chemical	D000638
+7083920	CID	D000638	D006327
+
+7269015|t|Busulfan-induced hemorrhagic cystitis.
+7269015|a|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.
+7269015	0	8	Busulfan	Chemical	D002066
+7269015	17	37	hemorrhagic cystitis	Disease	D006470|D003556	hemorrhagic|cystitis
+7269015	51	59	busulfan	Chemical	D002066
+7269015	68	87	hemorrhage cystitis	Disease	D006470|D003556	hemorrhage|cystitis
+7269015	219	227	busulfan	Chemical	D002066
+7269015	228	236	cystitis	Disease	D003556
+7269015	260	276	cyclophosphamide	Chemical	D003520
+7269015	285	293	cystitis	Disease	D003556
+7269015	375	383	busulfan	Chemical	D002066
+7269015	414	423	carcinoma	Disease	D002277
+7269015	CID	D002066	D003556
+7269015	CID	D002066	D006470
+
+7352670|t|Rebound hypertensive after sodium nitroprusside prevented by saralasin in rats.
+7352670|a|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.
+7352670	8	20	hypertensive	Disease	D006973
+7352670	27	47	sodium nitroprusside	Chemical	D009599
+7352670	61	70	saralasin	Chemical	D012504
+7352670	103	114	angiotensin	Chemical	D000809
+7352670	166	175	halothane	Chemical	D006221
+7352670	191	211	sodium nitroprusside	Chemical	D009599
+7352670	213	216	SNP	Chemical	D009599
+7352670	226	237	hypotension	Disease	D007022
+7352670	275	284	halothane	Chemical	D006221
+7352670	330	333	SNP	Chemical	D009599
+7352670	504	513	saralasin	Chemical	D012504
+7352670	542	556	angiotensin II	Chemical	D000804
+7352670	609	612	SNP	Chemical	D009599
+7352670	735	738	SNP	Chemical	D009599
+7352670	795	821	increase in blood pressure	Disease	D006973
+7352670	846	855	saralasin	Chemical	D012504
+7352670	919	922	SNP	Chemical	D009599
+7352670	1016	1025	saralasin	Chemical	D012504
+7352670	1078	1087	halothane	Chemical	D006221
+7352670	1146	1149	SNP	Chemical	D009599
+7352670	1172	1175	SNP	Chemical	D009599
+7352670	1231	1240	saralasin	Chemical	D012504
+7352670	1292	1303	angiotensin	Chemical	D000809
+7352670	1340	1351	hypotensive	Disease	D007022
+7352670	1363	1372	halothane	Chemical	D006221
+7352670	1377	1380	SNP	Chemical	D009599
+7352670	CID	D009599	D007022
+7352670	CID	D006221	D007022
+
+7504976|t|Toxic hepatitis induced by antithyroid drugs: four cases including one with cross-reactivity between carbimazole and benzylthiouracil.
+7504976|a|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.
+7504976	0	15	Toxic hepatitis	Disease	D056486
+7504976	101	112	carbimazole	Chemical	D002231
+7504976	117	133	benzylthiouracil	Chemical	C019269
+7504976	199	222	hepatic adverse effects	Disease	D056486
+7504976	329	344	hyperthyroidism	Disease	D006980
+7504976	464	479	toxic hepatitis	Disease	D056486
+7504976	569	590	cholestatic hepatitis	Disease	D002779|D056486	cholestatic|hepatitis
+7504976	602	613	carbimazole	Chemical	D002231
+7504976	615	628	N  omercazole	Chemical	D002231
+7504976	655	666	cholestatic	Disease	D002779
+7504976	682	691	hepatitis	Disease	D056486
+7504976	702	713	carbimazole	Chemical	D002231
+7504976	778	787	hepatitis	Disease	D056486
+7504976	809	825	Benzylthiouracil	Chemical	C019269
+7504976	827	835	Basd  ne	Chemical	C019269
+7504976	850	861	carbimazole	Chemical	D002231
+7504976	886	895	hepatitis	Disease	D056486
+7504976	1098	1109	neutropenia	Disease	D009503
+7504976	1123	1138	Toxic hepatitis	Disease	D056486
+7504976	1340	1354	hepatotoxicity	Disease	D056486
+7504976	CID	D002231	D056486
+7504976	CID	D002231	D002779
+
+7628595|t|Study of the role of vitamin B12 and folinic acid supplementation in preventing hematologic toxicity of zidovudine.
+7628595|a|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.
+7628595	21	32	vitamin B12	Chemical	D014805
+7628595	37	49	folinic acid	Chemical	D002955
+7628595	92	100	toxicity	Disease	D064420
+7628595	104	114	zidovudine	Chemical	D015215
+7628595	186	197	vitamin B12	Chemical	D014805
+7628595	202	214	folinic acid	Chemical	D002955
+7628595	245	255	zidovudine	Chemical	D015215
+7628595	257	260	ZDV	Chemical	D015215
+7628595	270	293	bone marrow suppression	Disease	D001855
+7628595	308	351	human immunodeficiency virus (HIV)-infected	Disease	D015658
+7628595	427	430	ZDV	Chemical	D015215
+7628595	493	505	folinic acid	Chemical	D002955
+7628595	538	549	vitamin B12	Chemical	D014805
+7628595	665	670	death	Disease	D003643
+7628595	842	853	vitamin B12	Chemical	D014805
+7628595	858	864	folate	Chemical	D005492
+7628595	1117	1125	toxicity	Disease	D064420
+7628595	1287	1298	vitamin B12	Chemical	D014805
+7628595	1302	1308	folate	Chemical	D005492
+7628595	1335	1351	myelosuppression	Disease	D001855
+7628595	1353	1364	Vitamin B12	Chemical	D014805
+7628595	1369	1381	folinic acid	Chemical	D002955
+7628595	1401	1404	ZDV	Chemical	D015215
+7628595	1460	1463	ZDV	Chemical	D015215
+7628595	1472	1485	myelotoxicity	Disease	D001855
+7628595	CID	D015215	D001855
+
+7858459|t|Acute confusion induced by a high-dose infusion of 5-fluorouracil and folinic acid.
+7858459|a|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.
+7858459	6	15	confusion	Disease	D003221
+7858459	51	65	5-fluorouracil	Chemical	D005472
+7858459	70	82	folinic acid	Chemical	D002955
+7858459	158	169	cisplatinum	Chemical	D002945
+7858459	171	180	etoposide	Chemical	D005047
+7858459	192	206	5-fluorouracil	Chemical	D005472
+7858459	234	246	folinic acid	Chemical	D002955
+7858459	265	287	gastric adenocarcinoma	Disease	D013274
+7858459	338	347	confusion	Disease	D003221
+7858459	349	363	disorientation	Disease	D003221
+7858459	368	380	irritability	Disease	D001523
+7858459	410	414	coma	Disease	D003128
+7858459	484	498	5-fluorouracil	Chemical	D005472
+7858459	503	515	folinic acid	Chemical	D002955
+7858459	591	605	5-fluorouracil	Chemical	D005472
+7858459	610	622	folinic acid	Chemical	D002955
+7858459	670	682	folinic acid	Chemical	D002955
+7858459	734	747	neurotoxicity	Disease	D020258
+7858459	765	779	5-fluorouracil	Chemical	D005472
+7858459	822	836	5-fluorouracil	Chemical	D005472
+7858459	837	850	neurotoxicity	Disease	D020258
+7858459	891	904	fluoroacetate	Chemical	D005463
+7858459	909	922	fluorocitrate	Chemical	C007744
+7858459	924	932	thiamine	Chemical	D013831
+7858459	948	961	dihydrouracil	Chemical	C007419
+7858459	998	1012	5-fluorouracil	Chemical	D005472
+7858459	1013	1025	folinic acid	Chemical	D002955
+7858459	1093	1100	cancers	Disease	D009369
+7858459	CID	D002955	D003221
+7858459	CID	D005472	D003128
+7858459	CID	D005472	D003221
+7858459	CID	D002955	D003128
+
+7862923|t|Effect of switching carbamazepine to oxcarbazepine on the plasma levels of neuroleptics. A case report.
+7862923|a|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.
+7862923	20	33	carbamazepine	Chemical	D002220
+7862923	37	50	oxcarbazepine	Chemical	C036006
+7862923	104	117	Carbamazepine	Chemical	D002220
+7862923	155	168	oxcarbazepine	Chemical	C036006
+7862923	198	211	schizophrenic	Disease	D012559
+7862923	215	232	organic psychotic	Disease	D019965
+7862923	262	273	haloperidol	Chemical	D006220
+7862923	275	289	chlorpromazine	Chemical	D002746
+7862923	293	302	clozapine	Chemical	D003024
+7862923	431	454	extrapyramidal symptoms	Disease	D001480
+7862923	615	628	carbamazepine	Chemical	D002220
+7862923	629	642	oxcarbazepine	Chemical	C036006
+7862923	CID	D006220	D001480
+7862923	CID	D002746	D001480
+7862923	CID	D003024	D001480
+7862923	CID	C036006	D001480
+
+7919560|t|Erythema multiforme and hypersensitivity myocarditis caused by ampicillin.
+7919560|a|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.
+7919560	0	19	Erythema multiforme	Disease	D004892
+7919560	24	52	hypersensitivity myocarditis	Disease	D009205
+7919560	63	73	ampicillin	Chemical	D000667
+7919560	106	125	erythema multiforme	Disease	D004892
+7919560	130	158	hypersensitivity myocarditis	Disease	D009205
+7919560	169	179	ampicillin	Chemical	D000667
+7919560	230	240	ampicillin	Chemical	D000667
+7919560	245	255	gentamicin	Chemical	D005839
+7919560	277	287	septicemia	Disease	D018805
+7919560	324	343	erythema multiforme	Disease	D004892
+7919560	348	372	congestive heart failure	Disease	D006333
+7919560	383	394	myocarditis	Disease	D009205
+7919560	434	452	methylprednisolone	Chemical	D008775
+7919560	525	535	ampicillin	Chemical	D000667
+7919560	573	583	infections	Disease	D007239
+7919560	592	611	erythema multiforme	Disease	D004892
+7919560	616	627	myocarditis	Disease	D009205
+7919560	646	676	drug-induced allergic reaction	Disease	D004342
+7919560	714	724	ampicillin	Chemical	D000667
+7919560	778	788	ampicillin	Chemical	D000667
+7919560	803	831	Hypersensitivity myocarditis	Disease	D009205
+7919560	873	880	allergy	Disease	D004342
+7919560	884	895	penicillins	Chemical	D010406
+7919560	CID	D000667	D004892
+7919560	CID	D000667	D004342
+7919560	CID	D000667	D009205
+
+8092427|t|Immediate allergic reactions to amoxicillin.
+8092427|a|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.
+8092427	10	28	allergic reactions	Disease	D004342
+8092427	32	43	amoxicillin	Chemical	D000658
+8092427	86	104	allergic reactions	Disease	D004342
+8092427	108	119	beta-lactam	Chemical	D047090
+8092427	306	314	allergic	Disease	D004342
+8092427	318	329	beta-lactam	Chemical	D047090
+8092427	366	374	allergic	Disease	D004342
+8092427	388	399	amoxicillin	Chemical	D000658
+8092427	401	403	AX	Chemical	D000658
+8092427	439	449	penicillin	Chemical	D010406
+8092427	494	525	benzylpenicilloyl-poly-L-lysine	Chemical	-1
+8092427	527	534	BPO-PLL	Chemical	-1
+8092427	537	555	benzylpenicilloate	Chemical	-1
+8092427	557	573	benzylpenicillin	Chemical	D010400
+8092427	575	577	PG	Chemical	D010400
+8092427	580	590	ampicillin	Chemical	D000667
+8092427	592	595	AMP	Chemical	D000667
+8092427	602	604	AX	Chemical	D000658
+8092427	615	622	BPO-PLL	Chemical	-1
+8092427	627	629	AX	Chemical	D000658
+8092427	677	680	BPO	Chemical	-1
+8092427	778	780	PG	Chemical	D010400
+8092427	799	801	AX	Chemical	D000658
+8092427	845	853	allergic	Disease	D004342
+8092427	857	868	beta-lactam	Chemical	D047090
+8092427	928	930	AX	Chemical	D000658
+8092427	931	938	allergy	Disease	D004342
+8092427	962	964	PG	Chemical	D010400
+8092427	966	977	Anaphylaxis	Disease	D000707
+8092427	1035	1044	urticaria	Disease	D014581
+8092427	1052	1062	angioedema	Disease	D000799
+8092427	1108	1111	BPO	Chemical	-1
+8092427	1150	1153	MDM	Disease	D007645
+8092427	1177	1179	PG	Chemical	D010400
+8092427	1197	1199	AX	Chemical	D000658
+8092427	1258	1260	AX	Chemical	D000658
+8092427	1289	1292	BPO	Chemical	-1
+8092427	1349	1351	AX	Chemical	D000658
+8092427	1369	1372	BPO	Chemical	-1
+8092427	1395	1397	AX	Chemical	D000658
+8092427	1474	1491	allergic reaction	Disease	D004342
+8092427	1495	1497	AX	Chemical	D000658
+8092427	1549	1551	AX	Chemical	D000658
+8092427	1567	1569	PG	Chemical	D010400
+8092427	1642	1644	AX	Chemical	D000658
+8092427	1645	1653	allergic	Disease	D004342
+8092427	1682	1684	PG	Chemical	D010400
+8092427	1763	1765	AX	Chemical	D000658
+8092427	CID	D000658	D000707
+8092427	CID	D000658	D004342
+8092427	CID	D000658	D000799
+
+8638206|t|Persistent paralysis after prolonged use of atracurium in the absence of corticosteroids.
+8638206|a|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.
+8638206	11	20	paralysis	Disease	D010243
+8638206	44	54	atracurium	Chemical	D001279
+8638206	222	231	paralysis	Disease	D010243
+8638206	330	348	vecuronium bromide	Chemical	D014673
+8638206	408	427	Atracurium besylate	Chemical	D001279
+8638206	444	464	benzylisoquinolinium	Chemical	-1
+8638206	574	583	paralysis	Disease	D010243
+8638206	646	656	atracurium	Chemical	D001279
+8638206	665	674	paralysis	Disease	D010243
+8638206	CID	D001279	D010243
+8638206	CID	D014673	D010243
+
+8669433|t|Habitual use of acetaminophen as a risk factor for chronic renal failure: a comparison with phenacetin.
+8669433|a|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.
+8669433	16	29	acetaminophen	Chemical	D000082
+8669433	51	72	chronic renal failure	Disease	D007676
+8669433	92	102	phenacetin	Chemical	D010615
+8669433	192	202	phenacetin	Chemical	D010615
+8669433	241	262	chronic renal failure	Disease	D007676
+8669433	267	290	end-stage renal disease	Disease	D007676
+8669433	292	296	ESRD	Disease	D007676
+8669433	385	395	phenacetin	Chemical	D010615
+8669433	592	605	acetaminophen	Chemical	D000082
+8669433	630	651	chronic renal failure	Disease	D007676
+8669433	656	660	ESRD	Disease	D007676
+8669433	739	749	phenacetin	Chemical	D010615
+8669433	754	767	acetaminophen	Chemical	D000082
+8669433	800	804	ESRD	Disease	D007676
+8669433	945	956	nephrotoxic	Disease	D007674
+8669433	1036	1049	acetaminophen	Chemical	D000082
+8669433	1167	1180	acetaminophen	Chemical	D000082
+8669433	1268	1278	phenacetin	Chemical	D010615
+8669433	1352	1365	acetaminophen	Chemical	D000082
+8669433	1394	1398	ESRD	Disease	D007676
+8669433	CID	D010615	D007676
+
+8690168|t|Reduction of heparan sulphate-associated anionic sites in the glomerular basement membrane of rats with streptozotocin-induced diabetic nephropathy.
+8690168|a|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.
+8690168	13	29	heparan sulphate	Chemical	D006497
+8690168	104	118	streptozotocin	Chemical	D013311
+8690168	127	147	diabetic nephropathy	Disease	D003928
+8690168	149	165	Heparan sulphate	Chemical	D006497
+8690168	276	284	diabetes	Disease	D003920
+8690168	288	302	streptozotocin	Chemical	D013311
+8690168	372	387	cuprolinic blue	Chemical	C015445
+8690168	496	512	heparan sulphate	Chemical	D006497
+8690168	532	547	cuprolinic blue	Chemical	C015445
+8690168	577	594	glycosaminoglycan	Chemical	D006025
+8690168	778	786	diabetic	Disease	D003920
+8690168	1116	1124	diabetic	Disease	D003920
+8690168	1158	1166	Diabetic	Disease	D003920
+8690168	1196	1207	albuminuria	Disease	D000419
+8690168	1358	1374	heparan sulphate	Chemical	D006497
+8690168	1792	1806	streptozotocin	Chemical	D013311
+8690168	1807	1815	diabetic	Disease	D003920
+8690168	1876	1892	heparan sulphate	Chemical	D006497
+8690168	CID	D013311	D003928
+
+8739323|t|Effect of some anticancer drugs and combined chemotherapy on renal toxicity.
+8739323|a|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.
+8739323	61	75	renal toxicity	Disease	D007674
+8739323	81	92	nephrotoxic	Disease	D007674
+8739323	128	143	nitrogranulogen	Chemical	D008466
+8739323	145	147	NG	Chemical	D008466
+8739323	150	162	methotrexate	Chemical	D008727
+8739323	164	167	MTX	Chemical	D008727
+8739323	170	184	5-fluorouracil	Chemical	D005472
+8739323	186	190	5-FU	Chemical	D005472
+8739323	196	212	cyclophosphamide	Chemical	D003520
+8739323	214	216	CY	Chemical	D003520
+8739323	256	259	MTX	Chemical	D008727
+8739323	262	266	5-FU	Chemical	D005472
+8739323	269	271	CY	Chemical	D003520
+8739323	351	361	creatinine	Chemical	D003404
+8739323	448	458	creatinine	Chemical	D003404
+8739323	538	541	MTX	Chemical	D008727
+8739323	607	617	creatinine	Chemical	D003404
+8739323	675	685	creatinine	Chemical	D003404
+8739323	756	758	NG	Chemical	D008466
+8739323	760	764	5-FU	Chemical	D005472
+8739323	769	771	CY	Chemical	D003520
+8739323	820	830	creatinine	Chemical	D003404
+8739323	864	874	creatinine	Chemical	D003404
+8739323	1051	1061	creatinine	Chemical	D003404
+8739323	1087	1097	creatinine	Chemical	D003404
+8739323	1165	1167	CY	Chemical	D003520
+8739323	1175	1195	hemorrhagic cystitis	Disease	D006470|D003556	hemorrhagic|cystitis
+8739323	1270	1274	5-FU	Chemical	D005472
+8739323	1279	1282	MTX	Chemical	D008727
+8739323	1353	1356	MTX	Chemical	D008727
+8739323	1358	1360	CY	Chemical	D003520
+8739323	1365	1367	NG	Chemical	D008466
+8739323	1409	1413	5-FU	Chemical	D005472
+8739323	1442	1445	MTX	Chemical	D008727
+8739323	1448	1452	5-FU	Chemical	D005472
+8739323	1455	1457	CY	Chemical	D003520
+8739323	1506	1520	nephrotoxicity	Disease	D007674
+8739323	1524	1527	MTX	Chemical	D008727
+8739323	1530	1534	5-FU	Chemical	D005472
+8739323	1537	1539	CY	Chemical	D003520
+8739323	CID	D003520	D006470
+8739323	CID	D003520	D003556
+
+8752018|t|Lithium-associated cognitive and functional deficits reduced by a switch to divalproex sodium: a case series.
+8752018|a|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.
+8752018	0	7	Lithium	Chemical	D008094
+8752018	19	52	cognitive and functional deficits	Disease	D003072
+8752018	76	93	divalproex sodium	Chemical	D014635
+8752018	122	129	Lithium	Chemical	D008094
+8752018	204	220	bipolar disorder	Disease	D001714
+8752018	312	319	lithium	Chemical	D008094
+8752018	329	337	polyuria	Disease	D011141
+8752018	342	348	tremor	Disease	D014202
+8752018	362	369	lithium	Chemical	D008094
+8752018	391	409	cognitive deficits	Disease	D003072
+8752018	411	429	loss of creativity	Disease	D003072
+8752018	435	457	functional impairments	Disease	D003072
+8752018	530	537	bipolar	Disease	D001714
+8752018	552	559	lithium	Chemical	D008094
+8752018	563	580	divalproex sodium	Chemical	D014635
+8752018	599	635	cognitive and functional impairments	Disease	D003072
+8752018	724	731	lithium	Chemical	D008094
+8752018	765	782	divalproex sodium	Chemical	D014635
+8752018	821	866	cognitive, motivational, or creative deficits	Disease	D003072
+8752018	881	888	lithium	Chemical	D008094
+8752018	896	903	bipolar	Disease	D001714
+8752018	954	971	divalproex sodium	Chemical	D014635
+8752018	1002	1009	lithium	Chemical	D008094
+8752018	1013	1020	bipolar	Disease	D001714
+8752018	1043	1061	cognitive deficits	Disease	D003072
+8752018	1063	1081	loss of creativity	Disease	D003072
+8752018	1087	1109	functional impairments	Disease	D003072
+8752018	CID	D008094	D003072
+
+9390208|t|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.
+9390208|a|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.
+9390208	43	56	breast cancer	Disease	D001943
+9390208	60	72	mitoxantrone	Chemical	D008942
+9390208	118	122	5-FU	Chemical	D005472
+9390208	127	137	leucovorin	Chemical	D002955
+9390208	139	142	MFL	Chemical	C085788
+9390208	195	203	toxicity	Disease	D064420
+9390208	237	250	breast cancer	Disease	D001943
+9390208	324	336	mitoxantrone	Chemical	D008942
+9390208	348	362	5-fluorouracil	Chemical	D005472
+9390208	364	368	5-FU	Chemical	D005472
+9390208	374	384	leucovorin	Chemical	D002955
+9390208	386	397	MFL regimen	Chemical	C085788
+9390208	568	581	breast cancer	Disease	D001943
+9390208	585	597	mitoxantrone	Chemical	D008942
+9390208	645	649	5-FU	Chemical	D005472
+9390208	677	687	leucovorin	Chemical	D002955
+9390208	909	922	anthracycline	Chemical	D018943
+9390208	1044	1055	MFL regimen	Chemical	C085788
+9390208	1104	1116	mitoxantrone	Chemical	D008942
+9390208	1492	1502	toxicities	Disease	D064420
+9390208	1508	1522	cardiotoxicity	Disease	D066126
+9390208	1527	1537	leukopenia	Disease	D007970
+9390208	1625	1633	toxicity	Disease	D064420
+9390208	1639	1650	MFL regimen	Chemical	C085788
+9390208	1705	1713	toxicity	Disease	D064420
+9390208	1771	1784	breast cancer	Disease	D001943
+9390208	1847	1870	impaired heart function	Disease	D006331
+9390208	CID	C085788	D006331
+9390208	CID	C085788	D007970
+
+9406968|t|Upregulation of the expression of vasopressin gene in the paraventricular and supraoptic nuclei of the lithium-induced diabetes insipidus rat.
+9406968|a|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.
+9406968	34	45	vasopressin	Chemical	D014667
+9406968	103	110	lithium	Chemical	D008094
+9406968	119	137	diabetes insipidus	Disease	D003919
+9406968	161	181	arginine vasopressin	Chemical	D001127
+9406968	183	186	AVP	Chemical	D001127
+9406968	280	287	lithium	Chemical	D008094
+9406968	289	291	Li	Chemical	D008094
+9406968	301	309	polyuria	Disease	D011141
+9406968	429	433	LiCl	Chemical	D018021
+9406968	476	484	polyuria	Disease	D011141
+9406968	490	492	Li	Chemical	D008094
+9406968	587	593	sodium	Chemical	D012964
+9406968	652	654	Li	Chemical	D008094
+9406968	725	728	AVP	Chemical	D001127
+9406968	748	751	AVP	Chemical	D001127
+9406968	812	814	Li	Chemical	D008094
+9406968	879	890	dehydration	Disease	D003681
+9406968	983	986	AVP	Chemical	D001127
+9406968	1011	1014	AVP	Chemical	D001127
+9406968	1061	1063	Li	Chemical	D008094
+9406968	1072	1090	diabetes insipidus	Disease	D003919
+9406968	CID	D018021	D011141
+
+9587734|t|Suxamethonium-induced cardiac arrest and death following 5 days of immobilization.
+9587734|a|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.
+9587734	0	13	Suxamethonium	Chemical	D013390
+9587734	22	36	cardiac arrest	Disease	D006323
+9587734	41	46	death	Disease	D003643
+9587734	122	136	cardiac arrest	Disease	D006323
+9587734	152	157	death	Disease	D003643
+9587734	173	186	hyperkalaemia	Disease	D006947
+9587734	208	221	suxamethonium	Chemical	D013390
+9587734	300	310	meningitis	Disease	D008581
+9587734	420	433	suxamethonium	Chemical	D013390
+9587734	435	446	bradycardia	Disease	D001919
+9587734	451	465	cardiac arrest	Disease	D006323
+9587734	552	561	potassium	Chemical	D011188
+9587734	764	777	hyperkalaemia	Disease	D006947
+9587734	810	823	suxamethonium	Chemical	D013390
+9587734	851	856	death	Disease	D003643
+9587734	871	887	hypersensitivity	Disease	D004342
+9587734	891	904	suxamethonium	Chemical	D013390
+9587734	CID	D013390	D004342
+9587734	CID	D013390	D006323
+9587734	CID	D013390	D006947
+9587734	CID	D013390	D001919
+
+9698967|t|An unusual toxic reaction to axillary block by mepivacaine with adrenaline.
+9698967|a|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.
+9698967	47	58	mepivacaine	Chemical	D008619
+9698967	64	74	adrenaline	Chemical	D004837
+9698967	79	105	increase in blood pressure	Disease	D006973
+9698967	122	141	atrial fibrillation	Disease	D001281
+9698967	143	152	agitation	Disease	D011595
+9698967	154	177	incomprehensible shouts	Disease	D019954
+9698967	182	203	loss of consciousness	Disease	D014474
+9698967	343	354	mepivacaine	Chemical	D008619
+9698967	373	383	adrenaline	Chemical	D004837
+9698967	412	435	Dupuytren's contracture	Disease	D004387
+9698967	473	482	labetalol	Chemical	D007741
+9698967	484	494	metoprolol	Chemical	D008790
+9698967	499	508	midazolam	Chemical	D008874
+9698967	655	674	atrial fibrillation	Disease	D001281
+9698967	872	883	mepivacaine	Chemical	D008619
+9698967	889	899	adrenaline	Chemical	D004837
+9698967	CID	D004837	D001281
+9698967	CID	D008619	D001281
+9698967	CID	D008619	D006973
+9698967	CID	D004837	D006973
+
+9855119|t|Clinical and histopathologic examination of renal allografts treated with tacrolimus (FK506) for at least one year.
+9855119|a|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.
+9855119	74	84	tacrolimus	Chemical	D016559
+9855119	86	91	FK506	Chemical	D016559
+9855119	235	245	tacrolimus	Chemical	D016559
+9855119	247	252	FK506	Chemical	D016559
+9855119	804	819	IgA nephropathy	Disease	D005922
+9855119	873	878	FK506	Chemical	D016559
+9855119	879	890	nephropathy	Disease	D007674
+9855119	914	919	FK506	Chemical	D016559
+9855119	920	931	nephropathy	Disease	D007674
+9855119	1029	1034	FK506	Chemical	D016559
+9855119	1035	1046	nephropathy	Disease	D007674
+9855119	1070	1075	FK506	Chemical	D016559
+9855119	1076	1087	nephropathy	Disease	D007674
+9855119	1225	1259	focal segmental glomerulosclerosis	Disease	D005923
+9855119	1297	1318	interstitial fibrosis	Disease	D005355
+9855119	1344	1354	creatinine	Chemical	D003404
+9855119	1399	1404	FK506	Chemical	D016559
+9855119	1405	1416	nephropathy	Disease	D007674
+9855119	1524	1529	FK506	Chemical	D016559
+9855119	1530	1541	nephropathy	Disease	D007674
+9855119	1610	1615	FK506	Chemical	D016559
+9855119	1616	1627	nephropathy	Disease	D007674
+9855119	1762	1767	FK506	Chemical	D016559
+9855119	1768	1779	nephropathy	Disease	D007674
+9855119	CID	D016559	D005923
+
+9869257|t|Memory facilitation and stimulation of endogenous nerve growth factor synthesis by the acetylcholine releaser PG-9.
+9869257|a|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.
+9869257	87	100	acetylcholine	Chemical	D000109
+9869257	110	114	PG-9	Chemical	C087567
+9869257	131	135	PG-9	Chemical	C087567
+9869257	137	178	3alpha-tropyl 2-(p-bromophenyl)propionate	Chemical	C087567
+9869257	185	198	acetylcholine	Chemical	D000109
+9869257	322	326	PG-9	Chemical	C087567
+9869257	407	414	amnesia	Disease	D000647
+9869257	469	480	scopolamine	Chemical	D012601
+9869257	513	525	S-(-)-ET-126	Chemical	C098725
+9869257	564	568	PG-9	Chemical	C087567
+9869257	648	655	amnesia	Disease	D000647
+9869257	743	747	PG-9	Chemical	C087567
+9869257	923	927	PG-9	Chemical	C087567
+9869257	1069	1073	PG-9	Chemical	C087567
+9869257	1194	1198	PG-9	Chemical	C087567
+9869257	1242	1246	PG-9	Chemical	C087567
+9869257	1371	1375	PG-9	Chemical	C087567
+9869257	CID	C098725	D000647
+9869257	CID	D012601	D000647
+
+10342929|t|Angioedema due to ACE inhibitors: common and inadequately diagnosed.
+10342929|a|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.
+10342929	0	10	Angioedema	Disease	D000799
+10342929	18	32	ACE inhibitors	Chemical	D000806
+10342929	96	106	angioedema	Disease	D000799
+10342929	114	159	angiotensin-converting enzyme (ACE) inhibitor	Chemical	D000806
+10342929	CID	D000806	D000799
+
+10457883|t|Recurarization in the recovery room.
+10457883|a|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.
+10457883	112	122	atracurium	Chemical	D001279
+10457883	217	235	respiratory arrest	Disease	D012131
+10457883	248	260	desaturation	Disease	D001049
+10457883	265	276	bradycardia	Disease	D001919
+10457883	353	375	neuromuscular blockade	Disease	D020879
+10457883	CID	D001279	D012131
+10457883	CID	D001279	D001919
+10457883	CID	D001279	D001049
+
+10739826|t|Recurrent use of newer oral contraceptives and the risk of venous thromboembolism.
+10739826|a|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.
+10739826	23	42	oral contraceptives	Chemical	D003276
+10739826	59	81	venous thromboembolism	Disease	D054556
+10739826	137	159	venous thromboembolism	Disease	D054556
+10739826	161	164	VTE	Disease	D054556
+10739826	188	207	oral contraceptives	Chemical	D003276
+10739826	209	211	OC	Chemical	D003276
+10739826	253	255	OC	Chemical	D003276
+10739826	388	391	VTE	Disease	D054556
+10739826	502	505	VTE	Disease	D054556
+10739826	718	721	VTE	Disease	D054556
+10739826	759	761	OC	Chemical	D003276
+10739826	1081	1084	VTE	Disease	D054556
+10739826	1283	1285	OC	Chemical	D003276
+10739826	CID	D003276	D054556
+
+10791295|t|Development of apomorphine-induced aggressive behavior: comparison of adult male and female Wistar rats.
+10791295|a|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.
+10791295	15	26	apomorphine	Chemical	D001058
+10791295	35	54	aggressive behavior	Disease	D010554
+10791295	124	135	apomorphine	Chemical	D001058
+10791295	172	191	aggressive behavior	Disease	D010554
+10791295	323	334	apomorphine	Chemical	D001058
+10791295	378	397	aggressive behavior	Disease	D010554
+10791295	441	455	aggressiveness	Disease	D010554
+10791295	567	581	aggressiveness	Disease	D010554
+10791295	684	695	apomorphine	Chemical	D001058
+10791295	704	723	aggressive behavior	Disease	D010554
+10791295	CID	D001058	D010554
+
+11147747|t|Serotonergic antidepressants and urinary incontinence.
+11147747|a|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.
+11147747	0	28	Serotonergic antidepressants	Chemical	D018490
+11147747	33	53	urinary incontinence	Disease	D014549
+11147747	64	92	serotonergic antidepressants	Chemical	D018490
+11147747	145	165	urinary incontinence	Disease	D014549
+11147747	325	337	incontinence	Disease	D014549
+11147747	351	362	venlafaxine	Chemical	C047426
+11147747	438	450	incontinence	Disease	D014549
+11147747	478	487	serotonin	Chemical	D012701
+11147747	508	518	paroxetine	Chemical	D017374
+11147747	523	533	sertraline	Chemical	D020280
+11147747	588	599	venlafaxine	Chemical	C047426
+11147747	651	668	lithium carbonate	Chemical	D016651
+11147747	732	744	incontinence	Disease	D014549
+11147747	774	786	incontinence	Disease	D014549
+11147747	800	828	serotonergic antidepressants	Chemical	D018490
+11147747	CID	D016651	D014549
+11147747	CID	D020280	D014549
+11147747	CID	D018490	D014549
+11147747	CID	D017374	D014549
+11147747	CID	C047426	D014549
+
+11198499|t|Hypotension following the initiation of tizanidine in a patient treated with an angiotensin converting enzyme inhibitor for chronic hypertension.
+11198499|a|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.
+11198499	0	11	Hypotension	Disease	D007022
+11198499	40	50	tizanidine	Chemical	C023754
+11198499	80	91	angiotensin	Chemical	D000809
+11198499	132	144	hypertension	Disease	D006973
+11198499	256	266	spasticity	Disease	D009128
+11198499	278	317	disorders of the central nervous system	Disease	D002493
+11198499	351	361	spasticity	Disease	D009128
+11198499	457	468	angiotensin	Chemical	D000809
+11198499	539	550	hypotension	Disease	D007022
+11198499	671	681	lisinopril	Chemical	D017706
+11198499	686	697	angiotensin	Chemical	D000809
+11198499	738	750	hypertension	Disease	D006973
+11198499	765	776	hypotension	Disease	D007022
+11198499	803	813	tizanidine	Chemical	C023754
+11198499	856	866	spasticity	Disease	D009128
+11198499	896	906	tizanidine	Chemical	C023754
+11198499	1005	1017	hypertension	Disease	D006973
+11198499	1021	1031	spasticity	Disease	D009128
+11198499	CID	C023754	D007022
+11198499	CID	D017706	D007022
+
+11391224|t|Peritubular capillary basement membrane reduplication in allografts and native kidney disease: a clinicopathologic study of 278 consecutive renal specimens.
+11391224|a|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.
+11391224	79	93	kidney disease	Disease	D007674
+11391224	207	232	transplant glomerulopathy	Disease	D007674
+11391224	234	236	TG	Disease	D007674
+11391224	607	609	TG	Disease	D007674
+11391224	667	685	glomerulonephritis	Disease	D005921
+11391224	687	716	chronic allograft nephropathy	Disease	D051436
+11391224	807	823	glomerulopathies	Disease	D007674
+11391224	844	870	thrombotic microangiopathy	Disease	D057049
+11391224	872	894	malignant hypertension	Disease	D006974
+11391224	902	924	interstitial nephritis	Disease	D009395
+11391224	930	952	acute tubular necrosis	Disease	D007683
+11391224	998	1000	TG	Disease	D007674
+11391224	1043	1045	TG	Disease	D007674
+11391224	1123	1145	malignant hypertension	Disease	D006974
+11391224	1147	1173	thrombotic microangiopathy	Disease	D057049
+11391224	1175	1190	lupus nephritis	Disease	D008181
+11391224	1192	1218	Henoch-Schonlein nephritis	Disease	D011695
+11391224	1231	1249	glomerulonephritis	Disease	D005921
+11391224	1255	1262	cocaine	Chemical	D003042
+11391224	1271	1290	acute renal failure	Disease	D058186
+11391224	1324	1326	TG	Disease	D007674
+11391224	1343	1356	renal failure	Disease	D051437
+11391224	1372	1383	proteinuria	Disease	D011507
+11391224	1548	1550	TG	Disease	D007674
+11391224	1631	1633	TG	Disease	D007674
+11391224	1681	1696	kidney diseases	Disease	D007674
+11391224	1750	1752	TG	Disease	D007674
+11391224	1779	1797	endothelial injury	Disease	D014947
+11391224	1809	1827	immunologic injury	Disease	D007154
+11391224	CID	D003042	D058186
+
+11426838|t|Conformationally restricted analogs of BD1008 and an antisense oligodeoxynucleotide targeting sigma1 receptors produce anti-cocaine effects in mice.
+11426838|a|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.
+11426838	39	45	BD1008	Chemical	C085527
+11426838	63	83	oligodeoxynucleotide	Chemical	D009838
+11426838	124	131	cocaine	Chemical	D003042
+11426838	149	156	Cocaine	Chemical	D003042
+11426838	378	384	BD1018	Chemical	-1
+11426838	386	450	3S-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane	Chemical	-1
+11426838	453	459	BD1063	Chemical	C093337
+11426838	461	511	1-[2-(3,4-dichlorophenyl)ethyl]-4-methylpiperazine	Chemical	C093337
+11426838	518	523	LR132	Chemical	-1
+11426838	819	827	dopamine	Chemical	D004298
+11426838	837	841	GABA	Chemical	D005680
+11426838	849	853	NMDA	Chemical	D016202
+11426838	915	921	BD1018	Chemical	-1
+11426838	923	929	BD1063	Chemical	C093337
+11426838	934	939	LR132	Chemical	-1
+11426838	965	972	cocaine	Chemical	D003042
+11426838	981	992	convulsions	Disease	D012640
+11426838	1038	1043	LR132	Chemical	-1
+11426838	1054	1061	cocaine	Chemical	D003042
+11426838	1234	1253	di-o-tolylguanidine	Chemical	C050232
+11426838	1255	1258	DTG	Chemical	C050232
+11426838	1297	1303	BD1031	Chemical	-1
+11426838	1305	1369	3R-1-[2-(3,4-dichlorophenyl)ethyl]-1,4-diazabicyclo[4.3.0]nonane	Chemical	-1
+11426838	1400	1408	toxicity	Disease	D064420
+11426838	1412	1419	cocaine	Chemical	D003042
+11426838	1495	1501	BD1018	Chemical	-1
+11426838	1503	1509	BD1063	Chemical	C093337
+11426838	1514	1519	LR132	Chemical	-1
+11426838	1582	1589	cocaine	Chemical	D003042
+11426838	1640	1647	cocaine	Chemical	D003042
+11426838	1730	1750	oligodeoxynucleotide	Chemical	D009838
+11426838	1822	1832	convulsive	Disease	D012640
+11426838	1870	1877	cocaine	Chemical	D003042
+11426838	1991	1998	cocaine	Chemical	D003042
+11426838	CID	D003042	D012640
+
+11569530|t|Pharmacokinetic/pharmacodynamic assessment of the effects of E4031, cisapride, terfenadine and terodiline on monophasic action potential duration in dog.
+11569530|a|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.
+11569530	61	66	E4031	Chemical	C063968
+11569530	68	77	cisapride	Chemical	D020117
+11569530	79	90	terfenadine	Chemical	D016593
+11569530	95	105	terodiline	Chemical	C010637
+11569530	157	176	Torsades de pointes	Disease	D016171
+11569530	178	181	TDP	Disease	D016171
+11569530	206	229	ventricular tachycardia	Disease	D017180
+11569530	320	323	TDP	Disease	D016171
+11569530	407	418	terfenadine	Chemical	D016593
+11569530	423	433	terodiline	Chemical	C010637
+11569530	475	478	TDP	Disease	D016171
+11569530	592	595	TDP	Disease	D016171
+11569530	615	626	terfenadine	Chemical	D016593
+11569530	628	638	terodiline	Chemical	C010637
+11569530	640	649	cisapride	Chemical	D020117
+11569530	654	659	E4031	Chemical	C063968
+11569530	1142	1153	terfenadine	Chemical	D016593
+11569530	1164	1174	terodiline	Chemical	C010637
+11569530	1184	1193	cisapride	Chemical	D020117
+11569530	1206	1211	E4031	Chemical	C063968
+11569530	1324	1327	TDP	Disease	D016171
+11569530	1343	1354	terfenadine	Chemical	D016593
+11569530	1356	1366	terodiline	Chemical	C010637
+11569530	1368	1377	cisapride	Chemical	D020117
+11569530	1619	1622	TDP	Disease	D016171
+11569530	CID	D016593	D016171
+11569530	CID	D020117	D016171
+11569530	CID	C010637	D016171
+
+11587867|t|Fatal myeloencephalopathy due to accidental intrathecal vincristin administration: a report of two cases.
+11587867|a|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.
+11587867	6	25	myeloencephalopathy	Disease	D001927
+11587867	56	66	vincristin	Chemical	D014750
+11587867	161	172	vincristine	Chemical	D014750
+11587867	222	250	acute lymphoblastic leucemia	Disease	D054198
+11587867	278	300	lymphoblastic lymphoma	Disease	D054198
+11587867	378	389	vincristine	Chemical	D014750
+11587867	447	490	opistothonus, sensory and motor dysfunction	Disease	D020258|D020258|D020258	opistothonus dysfunction|sensory dysfunction|motor dysfunction
+11587867	505	514	paralysis	Disease	D010243
+11587867	608	640	degeneration of myelin and axons	Disease	D003711|D009410	degeneration of myelin|degeneration of axons
+11587867	652	679	pseudocystic transformation	Disease	-1
+11587867	700	711	vincristine	Chemical	D014750
+11587867	970	981	vincristine	Chemical	D014750
+11587867	CID	D014750	D020258
+11587867	CID	D014750	D009410
+11587867	CID	D014750	D003711
+
+11679859|t|Intravenous administration of prochlorperazine by 15-minute infusion versus 2-minute bolus does not affect the incidence of akathisia: a prospective, randomized, controlled trial.
+11679859|a|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.
+11679859	30	46	prochlorperazine	Chemical	D011346
+11679859	124	133	akathisia	Disease	D017109
+11679859	230	239	akathisia	Disease	D017109
+11679859	276	292	prochlorperazine	Chemical	D011346
+11679859	514	530	prochlorperazine	Chemical	D011346
+11679859	535	543	headache	Disease	D006261
+11679859	545	551	nausea	Disease	D009325
+11679859	556	564	vomiting	Disease	D014839
+11679859	649	665	prochlorperazine	Chemical	D011346
+11679859	942	951	akathisia	Disease	D017109
+11679859	1061	1070	agitation	Disease	D011595
+11679859	1120	1129	akathisia	Disease	D017109
+11679859	1199	1208	akathisia	Disease	D017109
+11679859	1240	1248	headache	Disease	D006261
+11679859	1253	1259	nausea	Disease	D009325
+11679859	1487	1495	headache	Disease	D006261
+11679859	1516	1522	nausea	Disease	D009325
+11679859	1562	1571	akathisia	Disease	D017109
+11679859	1803	1811	headache	Disease	D006261
+11679859	1950	1956	nausea	Disease	D009325
+11679859	2040	2049	akathisia	Disease	D017109
+11679859	2055	2071	prochlorperazine	Chemical	D011346
+11679859	2201	2217	prochlorperazine	Chemical	D011346
+11679859	2238	2246	headache	Disease	D006261
+11679859	2251	2257	nausea	Disease	D009325
+11679859	CID	D011346	D017109
+
+12041669|t|Antithymocyte globulin in the treatment of D-penicillamine-induced aplastic anemia.
+12041669|a|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.
+12041669	0	22	Antithymocyte globulin	Chemical	D000961
+12041669	43	58	D-penicillamine	Chemical	D010396
+12041669	67	82	aplastic anemia	Disease	D000741
+12041669	107	129	antithymocyte globulin	Chemical	D000961
+12041669	142	157	aplastic anemia	Disease	D000741
+12041669	165	180	D-penicillamine	Chemical	D010396
+12041669	432	454	antithymocyte globulin	Chemical	D000961
+12041669	487	502	D-penicillamine	Chemical	D010396
+12041669	511	526	aplastic anemia	Disease	D000741
+12041669	CID	D010396	D000741
+
+12198388|t|The relationship between hippocampal acetylcholine release and cholinergic convulsant sensitivity in withdrawal seizure-prone and withdrawal seizure-resistant selected mouse lines.
+12198388|a|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.
+12198388	37	50	acetylcholine	Chemical	D000109
+12198388	112	119	seizure	Disease	D012640
+12198388	141	148	seizure	Disease	D012640
+12198388	402	409	alcohol	Chemical	D000431
+12198388	506	513	alcohol	Chemical	D000431
+12198388	571	578	ethanol	Chemical	D000431
+12198388	660	667	alcohol	Chemical	D000431
+12198388	686	693	Seizure	Disease	D012640
+12198388	758	766	nicotine	Chemical	D009538
+12198388	768	777	carbachol	Chemical	D002217
+12198388	782	793	neostigmine	Chemical	D009388
+12198388	854	860	tremor	Disease	D014202
+12198388	967	976	potassium	Chemical	D011188
+12198388	988	1001	acetylcholine	Chemical	D000109
+12198388	1003	1006	ACh	Chemical	D000109
+12198388	1054	1063	Potassium	Chemical	D011188
+12198388	1136	1139	ACh	Chemical	D000109
+12198388	1194	1205	convulsions	Disease	D012640
+12198388	1239	1249	convulsion	Disease	D012640
+12198388	1271	1279	nicotine	Chemical	D009538
+12198388	1281	1290	carbachol	Chemical	D002217
+12198388	1296	1307	neostigmine	Chemical	D009388
+12198388	1434	1437	ACh	Chemical	D000109
+12198388	1449	1452	KCl	Chemical	C522374
+12198388	1463	1466	ACh	Chemical	D000109
+12198388	1533	1536	ACh	Chemical	D000109
+12198388	1574	1577	KCl	Chemical	C522374
+12198388	1637	1640	ACh	Chemical	D000109
+12198388	1690	1701	convulsions	Disease	D012640
+12198388	1717	1720	ACh	Chemical	D000109
+12198388	1941	1952	convulsants	Disease	D012640
+12198388	1976	1983	ethanol	Chemical	D000431
+12198388	2044	2051	alcohol	Chemical	D000431
+12198388	2129	2140	convulsants	Disease	D012640
+12198388	CID	D009388	D012640
+12198388	CID	D009538	D012640
+12198388	CID	D002217	D012640
+
+12574103|t|Prenatal dexamethasone programs hypertension and renal injury in the rat.
+12574103|a|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.
+12574103	9	22	dexamethasone	Chemical	D003907
+12574103	32	44	hypertension	Disease	D006973
+12574103	49	61	renal injury	Disease	D007674
+12574103	238	251	dexamethasone	Chemical	D003907
+12574103	277	303	increase in blood pressure	Disease	D006973
+12574103	308	320	renal injury	Disease	D007674
+12574103	411	424	dexamethasone	Chemical	D003907
+12574103	558	571	dexamethasone	Chemical	D003907
+12574103	610	640	reduction in glomerular number	Disease	D007674
+12574103	862	875	dexamethasone	Chemical	D003907
+12574103	1025	1038	dexamethasone	Chemical	D003907
+12574103	1100	1124	elevated blood pressures	Disease	D006973
+12574103	1177	1207	reduction in glomerular number	Disease	D007674
+12574103	1226	1239	dexamethasone	Chemical	D003907
+12574103	1295	1313	glomerulosclerosis	Disease	D005921
+12574103	1364	1377	dexamethasone	Chemical	D003907
+12574103	1399	1429	reduction in glomerular number	Disease	D007674
+12574103	1431	1449	glomerulosclerosis	Disease	D005921
+12574103	1455	1467	hypertension	Disease	D006973
+12574103	1523	1535	Hypertension	Disease	D006973
+12574103	1636	1666	reduction in glomerular number	Disease	D007674
+12574103	1686	1716	reduction in glomerular number	Disease	D007674
+12574103	1762	1774	hypertension	Disease	D006973
+12574103	CID	D003907	D007674
+12574103	CID	D003907	D006973
+
+12615818|t|The risk of venous thromboembolism in women prescribed cyproterone acetate in combination with ethinyl estradiol: a nested cohort analysis and case-control study.
+12615818|a|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.
+12615818	12	34	venous thromboembolism	Disease	D054556
+12615818	55	74	cyproterone acetate	Chemical	D017373
+12615818	95	112	ethinyl estradiol	Chemical	D004997
+12615818	175	194	Cyproterone acetate	Chemical	D017373
+12615818	209	226	ethinyl estradiol	Chemical	D004997
+12615818	228	231	CPA	Chemical	D017373
+12615818	232	234	EE	Chemical	D004997
+12615818	290	294	acne	Disease	D000152
+12615818	299	308	hirsutism	Disease	D006628
+12615818	344	369	polycystic ovary syndrome	Disease	D011085
+12615818	371	375	PCOS	Disease	D011085
+12615818	434	456	venous thromboembolism	Disease	D054556
+12615818	458	461	VTE	Disease	D054556
+12615818	479	482	CPA	Chemical	D017373
+12615818	483	485	EE	Chemical	D004997
+12615818	522	541	oral contraceptives	Chemical	D003276
+12615818	816	820	acne	Disease	D000152
+12615818	822	831	hirsutism	Disease	D006628
+12615818	835	839	PCOS	Disease	D011085
+12615818	864	867	VTE	Disease	D054556
+12615818	884	887	CPA	Chemical	D017373
+12615818	888	890	EE	Chemical	D004997
+12615818	943	946	CPA	Chemical	D017373
+12615818	947	949	EE	Chemical	D004997
+12615818	1244	1247	CPA	Chemical	D017373
+12615818	1248	1250	EE	Chemical	D004997
+12615818	1392	1395	VTE	Disease	D054556
+12615818	1423	1426	CPA	Chemical	D017373
+12615818	1427	1429	EE	Chemical	D004997
+12615818	1444	1448	acne	Disease	D000152
+12615818	1450	1459	hirsutism	Disease	D006628
+12615818	1463	1467	PCOS	Disease	D011085
+12615818	CID	D017373	D054556
+12615818	CID	D004997	D054556
+
+12789195|t|Pseudoacromegaly induced by the long-term use of minoxidil.
+12789195|a|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.
+12789195	0	16	Pseudoacromegaly	Disease	D004194
+12789195	49	58	minoxidil	Chemical	D008914
+12789195	60	70	Acromegaly	Disease	D000172
+12789195	77	95	endocrine disorder	Disease	D004700
+12789195	270	281	hypertrophy	Disease	D006984
+12789195	356	377	cutis verticis gyrata	Disease	C535610
+12789195	379	395	Pseudoacromegaly	Disease	D004194
+12789195	571	587	pseudoacromegaly	Disease	D004194
+12789195	628	637	minoxidil	Chemical	D008914
+12789195	698	714	pseudoacromegaly	Disease	D004194
+12789195	735	744	minoxidil	Chemical	D008914
+12789195	CID	D008914	D000172
+
+12820454|t|Combined androgen blockade-induced anemia in prostate cancer patients without bone involvement.
+12820454|a|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.
+12820454	35	41	anemia	Disease	D000740
+12820454	45	60	prostate cancer	Disease	D011471
+12820454	186	192	anemia	Disease	D000740
+12820454	196	211	prostate cancer	Disease	D011471
+12820454	307	331	prostatic adenocarcinoma	Disease	D000230
+12820454	445	463	leuprolide acetate	Chemical	D016729
+12820454	465	471	LHRH-A	Chemical	D016729
+12820454	525	534	flutamide	Chemical	D005485
+12820454	572	578	anemia	Disease	D000740
+12820454	708	720	Testosterone	Chemical	D013739
+12820454	1193	1199	anemia	Disease	D000740
+12820454	1292	1298	anemia	Disease	D000740
+12820454	1377	1383	anemia	Disease	D000740
+12820454	1473	1479	anemia	Disease	D000740
+12820454	1554	1560	anemia	Disease	D000740
+12820454	1730	1736	anemia	Disease	D000740
+12820454	1740	1755	prostate cancer	Disease	D011471
+12820454	1963	1969	anemia	Disease	D000740
+12820454	2160	2166	anemia	Disease	D000740
+12820454	2186	2201	prostate cancer	Disease	D011471
+12820454	CID	D016729	D000740
+12820454	CID	D005485	D000740
+
+14657095|t|Reversible dilated cardiomyopathy related to amphotericin B therapy.
+14657095|a|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.
+14657095	11	33	dilated cardiomyopathy	Disease	D002311
+14657095	45	59	amphotericin B	Chemical	D000666
+14657095	105	127	dilated cardiomyopathy	Disease	D002311
+14657095	152	165	heart failure	Disease	D006333
+14657095	197	211	amphotericin B	Chemical	D000666
+14657095	213	216	AmB	Chemical	D000666
+14657095	235	253	coccidioidomycosis	Disease	D003047
+14657095	295	308	heart failure	Disease	D006333
+14657095	324	336	posaconazole	Chemical	C101425
+14657095	357	360	AmB	Chemical	D000666
+14657095	427	435	toxicity	Disease	D064420
+14657095	439	442	AmB	Chemical	D000666
+14657095	CID	D000666	D006333
+14657095	CID	D000666	D002311
+
+14765563|t|Risks of the consumption of beverages containing quinine.
+14765563|a|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.
+14765563	49	56	quinine	Chemical	D011803
+14765563	133	153	nocturnal leg cramps	Disease	D020922
+14765563	190	197	quinine	Chemical	D011803
+14765563	331	338	quinine	Chemical	D011803
+14765563	351	377	neurological complications	Disease	D002493
+14765563	389	398	confusion	Disease	D003221
+14765563	423	431	seizures	Disease	D012640
+14765563	437	441	coma	Disease	D003128
+14765563	523	530	quinine	Chemical	D011803
+14765563	CID	D011803	D003221
+14765563	CID	D011803	D003128
+14765563	CID	D011803	D012640
+
+15036754|t|Organophosphate-induced convulsions and prevention of neuropathological damages.
+15036754|a|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.
+15036754	0	15	Organophosphate	Chemical	D010755
+15036754	24	35	convulsions	Disease	D012640
+15036754	54	79	neuropathological damages	Disease	D004194
+15036754	86	102	organophosphorus	Chemical	D010755
+15036754	104	106	OP	Chemical	D010755
+15036754	121	147	diisopropylfluorophosphate	Chemical	D007531
+15036754	149	152	DFP	Chemical	D007531
+15036754	155	160	sarin	Chemical	D012524
+15036754	165	170	soman	Chemical	D012999
+15036754	272	280	toxicity	Disease	D064420
+15036754	284	287	OPs	Chemical	D010755
+15036754	395	408	acetylcholine	Chemical	D000109
+15036754	410	413	ACh	Chemical	D000109
+15036754	516	519	DFP	Chemical	D007531
+15036754	635	657	pralidoxime-2-chloride	Chemical	D011220
+15036754	659	663	2PAM	Chemical	D011220
+15036754	697	705	diazepam	Chemical	D003975
+15036754	727	736	adenosine	Chemical	D000241
+15036754	754	780	N(6)-cyclopentyl adenosine	Chemical	C048599
+15036754	782	785	CPA	Chemical	C048599
+15036754	803	807	NMDA	Chemical	D016202
+15036754	828	847	dizocilpine maleate	Chemical	D016291
+15036754	935	951	atropine sulfate	Chemical	D001285
+15036754	1023	1026	DFP	Chemical	D007531
+15036754	1054	1070	atropine sulfate	Chemical	D001285
+15036754	1133	1136	DFP	Chemical	D007531
+15036754	1210	1213	DFP	Chemical	D007531
+15036754	1247	1250	DFP	Chemical	D007531
+15036754	1251	1259	atropine	Chemical	D001285
+15036754	1282	1284	OP	Chemical	D010755
+15036754	1293	1301	toxicity	Disease	D064420
+15036754	1314	1317	CPA	Chemical	C048599
+15036754	1319	1327	diazepam	Chemical	D003975
+15036754	1331	1335	2PAM	Chemical	D011220
+15036754	1364	1367	DFP	Chemical	D007531
+15036754	1368	1376	atropine	Chemical	D001285
+15036754	1462	1471	poisoning	Disease	D011041
+15036754	1473	1481	Atropine	Chemical	D001285
+15036754	1482	1487	MK801	Chemical	D016291
+15036754	1536	1539	DFP	Chemical	D007531
+15036754	1540	1548	toxicity	Disease	D064420
+15036754	1565	1568	CPA	Chemical	C048599
+15036754	1570	1578	diazepam	Chemical	D003975
+15036754	1583	1587	2PAM	Chemical	D011220
+15036754	1608	1616	atropine	Chemical	D001285
+15036754	1662	1671	poisoning	Disease	D011041
+15036754	1693	1701	toxicity	Disease	D064420
+15036754	1705	1708	DFP	Chemical	D007531
+15036754	CID	D007531	D012640
+
+15145918|t|Differential modulation by estrogen of alpha2-adrenergic and I1-imidazoline receptor-mediated hypotension in female rats.
+15145918|a|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.
+15145918	27	35	estrogen	Chemical	D004967
+15145918	64	75	imidazoline	Chemical	D048288
+15145918	94	105	hypotension	Disease	D007022
+15145918	150	158	estrogen	Chemical	D004967
+15145918	184	195	hypotensive	Disease	D007022
+15145918	206	215	clonidine	Chemical	D003000
+15145918	394	402	estrogen	Chemical	D004967
+15145918	514	525	rilmenidine	Chemical	C032302
+15145918	545	561	alpha-methyldopa	Chemical	D008750
+15145918	822	830	estrogen	Chemical	D004967
+15145918	1207	1218	rilmenidine	Chemical	C032302
+15145918	1222	1238	alpha-methyldopa	Chemical	D008750
+15145918	1256	1267	hypotension	Disease	D007022
+15145918	1402	1418	alpha-methyldopa	Chemical	D008750
+15145918	1451	1462	hypotensive	Disease	D007022
+15145918	1475	1491	alpha-methyldopa	Chemical	D008750
+15145918	1521	1532	rilmenidine	Chemical	C032302
+15145918	1533	1544	hypotension	Disease	D007022
+15145918	1559	1575	alpha-methyldopa	Chemical	D008750
+15145918	1576	1587	hypotension	Disease	D007022
+15145918	1650	1678	a reduced locomotor activity	Disease	D001523
+15145918	1702	1718	17beta-estradiol	Chemical	D004958
+15145918	1826	1842	alpha-methyldopa	Chemical	D008750
+15145918	1896	1904	estrogen	Chemical	D004967
+15145918	1956	1967	hypotension	Disease	D007022
+15145918	2026	2042	alpha-methyldopa	Chemical	D008750
+15145918	2043	2051	estrogen	Chemical	D004967
+15145918	CID	C032302	D007022
+15145918	CID	D008750	D007022
+
+15233872|t|Cardioprotective effect of tincture of Crataegus on isoproterenol-induced myocardial infarction in rats.
+15233872|a|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.
+15233872	27	48	tincture of Crataegus	Chemical	C007145
+15233872	52	65	isoproterenol	Chemical	D007545
+15233872	74	95	myocardial infarction	Disease	D009203
+15233872	105	126	Tincture of Crataegus	Chemical	C007145
+15233872	128	131	TCR	Chemical	C007145
+15233872	137	181	alcoholic extract of the berries of hawthorn	Chemical	C007145
+15233872	183	202	Crataegus oxycantha	Chemical	C007145
+15233872	316	319	TCR	Chemical	C007145
+15233872	346	367	myocardial infarction	Disease	D009203
+15233872	393	396	TCR	Chemical	C007145
+15233872	552	565	isoproterenol	Chemical	D007545
+15233872	635	638	TCR	Chemical	C007145
+15233872	653	666	isoproterenol	Chemical	D007545
+15233872	746	749	ADP	Chemical	D000244
+15233872	761	767	oxygen	Chemical	D010100
+15233872	807	810	TCR	Chemical	C007145
+15233872	861	874	isoproterenol	Chemical	D007545
+15233872	929	932	TCR	Chemical	C007145
+15233872	983	996	isoproterenol	Chemical	D007545
+15233872	CID	D007545	D009203
+
+15458908|t|Safety and adverse effects associated with raloxifene: multiple outcomes of raloxifene evaluation.
+15458908|a|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
+15458908	43	53	raloxifene	Chemical	D020849
+15458908	76	86	raloxifene	Chemical	D020849
+15458908	135	145	raloxifene	Chemical	D020849
+15458908	201	209	estrogen	Chemical	D004967
+15458908	221	230	tamoxifen	Chemical	D013629
+15458908	266	276	Raloxifene	Chemical	D020849
+15458908	377	389	osteoporosis	Disease	D010024
+15458908	423	433	raloxifene	Chemical	D020849
+15458908	484	506	venous thromboembolism	Disease	D054556
+15458908	508	517	cataracts	Disease	D002386
+15458908	519	538	gallbladder disease	Disease	D005705
+15458908	544	577	endometrial hyperplasia or cancer	Disease	D004714|D016889	endometrial hyperplasia|endometrial cancer
+15458908	626	636	raloxifene	Chemical	D020849
+15458908	679	701	venous thromboembolism	Disease	D054556
+15458908	938	948	raloxifene	Chemical	D020849
+15458908	1088	1098	Raloxifene	Chemical	D020849
+15458908	1125	1134	cataracts	Disease	D002386
+15458908	1161	1180	gallbladder disease	Disease	D005705
+15458908	1207	1230	endometrial hyperplasia	Disease	D004714
+15458908	1260	1278	endometrial cancer	Disease	D016889
+15458908	1317	1327	Raloxifene	Chemical	D020849
+15458908	1370	1392	venous thromboembolism	Disease	D054556
+15458908	1430	1439	cataracts	Disease	D002386
+15458908	1441	1460	gallbladder disease	Disease	D005705
+15458908	1462	1485	endometrial hyperplasia	Disease	D004714
+15458908	1490	1508	endometrial cancer	Disease	D016889
+15458908	CID	D020849	D054556
+
+15737522|t|Ceftriaxone-associated biliary pseudolithiasis in paediatric surgical patients.
+15737522|a|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.
+15737522	0	11	Ceftriaxone	Chemical	D002443
+15737522	23	46	biliary pseudolithiasis	Disease	D001660
+15737522	102	113	ceftriaxone	Chemical	D002443
+15737522	123	138	pseudolithiasis	Disease	D001660
+15737522	228	251	gallbladder dysfunction	Disease	D005705
+15737522	309	324	pseudolithiasis	Disease	D001660
+15737522	409	424	pseudolithiasis	Disease	D001660
+15737522	467	478	ceftriaxone	Chemical	D002443
+15737522	572	583	ceftriaxone	Chemical	D002443
+15737522	721	736	pseudolithiasis	Disease	D001660
+15737522	884	899	pseudolithiasis	Disease	D001660
+15737522	963	978	pseudolithiasis	Disease	D001660
+15737522	CID	D002443	D001660
+
+16005948|t|Evaluation of the anticocaine monoclonal antibody GNC92H2 as an immunotherapy for cocaine overdose.
+16005948|a|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.
+16005948	50	57	GNC92H2	Chemical	-1
+16005948	82	98	cocaine overdose	Disease	D062787
+16005948	119	126	cocaine	Chemical	D003042
+16005948	179	195	cocaine overdose	Disease	D062787
+16005948	418	425	GNC92H2	Chemical	-1
+16005948	456	472	cocaine overdose	Disease	D062787
+16005948	603	610	cocaine	Chemical	D003042
+16005948	615	622	GNC92H2	Chemical	-1
+16005948	663	670	GNC92H2	Chemical	-1
+16005948	729	736	cocaine	Chemical	D003042
+16005948	772	779	cocaine	Chemical	D003042
+16005948	780	788	toxicity	Disease	D064420
+16005948	826	833	GNC92H2	Chemical	-1
+16005948	897	905	seizures	Disease	D012640
+16005948	920	925	death	Disease	D003643
+16005948	947	954	GNC92H2	Chemical	-1
+16005948	965	970	death	Disease	D003643
+16005948	981	988	cocaine	Chemical	D003042
+16005948	1047	1054	GNC92H2	Chemical	-1
+16005948	1085	1101	cocaine overdose	Disease	D062787
+16005948	CID	D003042	D012640
+
+16167916|t|The effects of short-term raloxifene therapy on fibrinolysis markers: TAFI, tPA, and PAI-1.
+16167916|a|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.
+16167916	26	36	raloxifene	Chemical	D020849
+16167916	332	342	raloxifene	Chemical	D020849
+16167916	430	440	osteopenia	Disease	D001851
+16167916	444	456	osteoporosis	Disease	D010024
+16167916	548	572	raloxifene hydrochloride	Chemical	D020849
+16167916	590	597	calcium	Chemical	D002118
+16167916	658	665	calcium	Chemical	D002118
+16167916	977	987	raloxifene	Chemical	D020849
+16167916	1289	1299	amenorrhea	Disease	D000568
+16167916	1372	1394	venous thromboembolism	Disease	D054556
+16167916	1402	1412	raloxifene	Chemical	D020849
+16167916	CID	D020849	D054556
+
+16403073|t|Ketoconazole induced torsades de pointes without concomitant use of QT interval-prolonging drug.
+16403073|a|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.
+16403073	0	12	Ketoconazole	Chemical	D007654
+16403073	21	40	torsades de pointes	Disease	D016171
+16403073	97	109	Ketoconazole	Chemical	D007654
+16403073	223	246	coronary artery disease	Disease	D003324
+16403073	272	293	prolonged QT interval	Disease	D008133
+16403073	298	317	torsades de pointes	Disease	D016171
+16403073	319	322	TdP	Disease	D016171
+16403073	337	349	ketoconazole	Chemical	D007654
+16403073	367	383	fungal infection	Disease	D009181
+16403073	439	451	ketoconazole	Chemical	D007654
+16403073	614	626	ketoconazole	Chemical	D007654
+16403073	668	671	TdP	Disease	D016171
+16403073	703	715	ketoconazole	Chemical	D007654
+16403073	775	791	long QT syndrome	Disease	D008133
+16403073	CID	D007654	D016171
+16403073	CID	D007654	D008133
+
+16755009|t|Pharmacological evidence for the potential of Daucus carota in the management of cognitive dysfunctions.
+16755009|a|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.
+16755009	81	103	cognitive dysfunctions	Disease	D003072
+16755009	221	232	cholesterol	Chemical	D002784
+16755009	297	327	extract of Daucus carota seeds	Chemical	D010936
+16755009	329	332	DCE	Chemical	D010936
+16755009	582	590	Diazepam	Chemical	D003975
+16755009	593	604	scopolamine	Chemical	D012601
+16755009	625	632	amnesia	Disease	D000647
+16755009	680	683	DCE	Chemical	D010936
+16755009	822	825	DCE	Chemical	D010936
+16755009	1061	1064	DCE	Chemical	D010936
+16755009	1078	1085	amnesia	Disease	D000647
+16755009	1097	1108	scopolamine	Chemical	D012601
+16755009	1131	1139	diazepam	Chemical	D003975
+16755009	1157	1178	Daucus carota extract	Chemical	D010936
+16755009	1268	1279	cholesterol	Chemical	D002784
+16755009	1379	1382	DCE	Chemical	D010936
+16755009	1489	1500	cholesterol	Chemical	D002784
+16755009	1588	1591	DCE	Chemical	D010936
+16755009	1604	1607	DCE	Chemical	D010936
+16755009	1662	1684	cognitive dysfunctions	Disease	D003072
+16755009	1771	1782	cholesterol	Chemical	D002784
+16755009	CID	D003975	D000647
+16755009	CID	D012601	D000647
+
+16904497|t|Cauda equina syndrome after epidural steroid injection: a case report.
+16904497|a|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.
+16904497	0	21	Cauda equina syndrome	Disease	D011128
+16904497	37	44	steroid	Chemical	D013256
+16904497	128	141	radiculopathy	Disease	D011843
+16904497	173	180	steroid	Chemical	D013256
+16904497	244	265	Cauda equina syndrome	Disease	D011128
+16904497	347	368	cauda equina syndrome	Disease	D011128
+16904497	410	423	triamcinolone	Chemical	D014221
+16904497	428	439	bupivacaine	Chemical	D002045
+16904497	485	512	low back and right leg pain	Disease	D017116|D010146	low back pain|pain
+16904497	540	547	steroid	Chemical	D013256
+16904497	808	819	bupivacaine	Chemical	D002045
+16904497	824	847	triamcinolone diacetate	Chemical	C030262
+16904497	975	983	numbness	Disease	D006987
+16904497	988	1012	lower extremity weakness	Disease	D020335
+16904497	1049	1066	loss of sensation	Disease	D006987
+16904497	1538	1545	steroid	Chemical	D013256
+16904497	1616	1640	neurologic deterioration	Disease	D009422
+16904497	1656	1663	steroid	Chemical	D013256
+16904497	CID	C030262	D011128
+16904497	CID	D002045	D011128
+
+16938416|t|High-dose testosterone is associated with atherosclerosis in postmenopausal women.
+16938416|a|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.
+16938416	10	22	testosterone	Chemical	D013739
+16938416	42	57	atherosclerosis	Disease	D050197
+16938416	151	166	atherosclerosis	Disease	D050197
+16938416	373	381	estrogen	Chemical	D004967
+16938416	382	394	testosterone	Chemical	D013739
+16938416	404	438	estradiol- and testosterone esters	Chemical	C032109
+16938416	451	466	atherosclerosis	Disease	D050197
+16938416	475	490	atherosclerosis	Disease	D050197
+16938416	617	632	atherosclerosis	Disease	D050197
+16938416	815	830	atherosclerosis	Disease	D050197
+16938416	906	921	atherosclerosis	Disease	D050197
+16938416	1119	1127	diabetes	Disease	D003920
+16938416	1129	1140	cholesterol	Chemical	D002784
+16938416	1176	1183	alcohol	Chemical	D000431
+16938416	1295	1307	testosterone	Chemical	D013739
+16938416	1337	1352	atherosclerosis	Disease	D050197
+16938416	CID	D013739	D050197
+
+17147461|t|Sirolimus-associated proteinuria and renal dysfunction.
+17147461|a|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.
+17147461	0	9	Sirolimus	Chemical	D020123
+17147461	21	32	proteinuria	Disease	D011507
+17147461	37	54	renal dysfunction	Disease	D007674
+17147461	56	65	Sirolimus	Chemical	D020123
+17147461	206	215	rapamycin	Chemical	D020123
+17147461	232	241	Sirolimus	Chemical	D020123
+17147461	356	367	nephropathy	Disease	D007674
+17147461	396	414	glomerulonephritis	Disease	D005921
+17147461	416	428	autoimmunity	Disease	D001327
+17147461	430	451	cystic renal diseases	Disease	D052177
+17147461	456	468	renal cancer	Disease	D007680
+17147461	501	510	sirolimus	Chemical	D020123
+17147461	629	640	nephrotoxic	Disease	D007674
+17147461	714	723	sirolimus	Chemical	D020123
+17147461	743	754	proteinuria	Disease	D011507
+17147461	759	782	acute renal dysfunction	Disease	D058186
+17147461	844	864	chronic renal damage	Disease	D051436
+17147461	884	893	sirolimus	Chemical	D020123
+17147461	905	916	proteinuria	Disease	D011507
+17147461	1075	1084	sirolimus	Chemical	D020123
+17147461	1206	1229	acute renal dysfunction	Disease	D058186
+17147461	1246	1255	sirolimus	Chemical	D020123
+17147461	1522	1531	sirolimus	Chemical	D020123
+17147461	1558	1567	sirolimus	Chemical	D020123
+17147461	1624	1635	proteinuria	Disease	D011507
+17147461	1663	1674	angiotensin	Chemical	D000809
+17147461	1707	1721	angiotensin II	Chemical	D000804
+17147461	1743	1754	proteinuria	Disease	D011507
+17147461	1848	1857	sirolimus	Chemical	D020123
+17147461	CID	D020123	D007674
+17147461	CID	D020123	D011507
+
+17241784|t|Progressive myopathy with up-regulation of MHC-I associated with statin therapy.
+17241784|a|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.
+17241784	12	20	myopathy	Disease	D009135
+17241784	65	71	statin	Chemical	D019821
+17241784	81	88	Statins	Chemical	D019821
+17241784	113	121	myopathy	Disease	D009135
+17241784	126	138	hyperCKaemia	Disease	-1
+17241784	233	240	statins	Chemical	D019821
+17241784	254	262	myopathy	Disease	D009135
+17241784	391	399	necrosis	Disease	D009336
+17241784	534	542	necrotic	Disease	D009336
+17241784	617	629	prednisolone	Chemical	D011239
+17241784	634	646	methotrexate	Chemical	D008727
+17241784	711	718	statins	Chemical	D019821
+17241784	751	759	myopathy	Disease	D009135
+17241784	868	876	myopathy	Disease	D009135
+17241784	923	930	statins	Chemical	D019821
+17241784	CID	D019821	D009336
+17241784	CID	D019821	D009135
+
+17261653|t|Direct inhibition of cardiac hyperpolarization-activated cyclic nucleotide-gated pacemaker channels by clonidine.
+17261653|a|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.
+17261653	57	74	cyclic nucleotide	Chemical	D009712
+17261653	103	112	clonidine	Chemical	D003000
+17261653	215	237	cardiovascular disease	Disease	D002318
+17261653	249	259	arrhythmia	Disease	D001145
+17261653	261	283	coronary heart disease	Disease	D003327
+17261653	297	310	heart failure	Disease	D006333
+17261653	435	444	clonidine	Chemical	D003000
+17261653	538	547	clonidine	Chemical	D003000
+17261653	586	595	clonidine	Chemical	D003000
+17261653	855	864	clonidine	Chemical	D003000
+17261653	875	884	clonidine	Chemical	D003000
+17261653	957	966	Clonidine	Chemical	D003000
+17261653	975	986	bradycardia	Disease	D001919
+17261653	1134	1143	clonidine	Chemical	D003000
+17261653	1247	1256	Clonidine	Chemical	D003000
+17261653	1399	1416	cyclic nucleotide	Chemical	D009712
+17261653	1513	1522	clonidine	Chemical	D003000
+17261653	1791	1800	clonidine	Chemical	D003000
+17261653	1839	1848	clonidine	Chemical	D003000
+17261653	CID	D003000	D001919
+
+17343925|t|Influence of smoking on developing cochlea. Does smoking during pregnancy affect the amplitudes of transient evoked otoacoustic emissions in newborns?
+17343925|a|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.
+17343925	13	20	smoking	Chemical	D012906
+17343925	49	56	smoking	Chemical	D012906
+17343925	179	186	smoking	Chemical	D012906
+17343925	242	249	smoking	Chemical	D012906
+17343925	326	333	smoking	Chemical	D012906
+17343925	370	382	hearing loss	Disease	D034381
+17343925	463	470	smoking	Chemical	D012906
+17343925	612	630	hearing impairment	Disease	D034381
+17343925	703	710	smoking	Chemical	D012906
+17343925	1331	1361	decreases of TEOAEs amplitudes	Disease	-1
+17343925	1551	1558	smoking	Chemical	D012906
+17343925	1800	1807	smoking	Chemical	D012906
+17343925	CID	D012906	D034381
+
+17400887|t|Neuroinflammation and behavioral abnormalities after neonatal terbutaline treatment in rats: implications for autism.
+17400887|a|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.
+17400887	0	17	Neuroinflammation	Disease	D020078
+17400887	22	46	behavioral abnormalities	Disease	D001523
+17400887	62	73	terbutaline	Chemical	D013726
+17400887	110	116	autism	Disease	D001321
+17400887	118	124	Autism	Disease	D001321
+17400887	130	157	neurodevelopmental disorder	Disease	D002658
+17400887	196	239	deficits in communication and social skills	Disease	D003147
+17400887	244	264	repetitive behaviors	Disease	D001523
+17400887	386	392	autism	Disease	D001321
+17400887	394	405	Terbutaline	Chemical	D013726
+17400887	451	464	preterm labor	Disease	D007752
+17400887	517	523	autism	Disease	D001321
+17400887	570	581	terbutaline	Chemical	D013726
+17400887	702	713	terbutaline	Chemical	D013726
+17400887	886	897	terbutaline	Chemical	D013726
+17400887	1103	1114	terbutaline	Chemical	D013726
+17400887	1173	1184	terbutaline	Chemical	D013726
+17400887	1545	1569	behavioral abnormalities	Disease	D001523
+17400887	1601	1607	autism	Disease	D001321
+17400887	1712	1737	autism spectrum disorders	Disease	D002659
+17400887	CID	D013726	D001321
+
+17612891|t|Acute myocarditis associated with clozapine.
+17612891|a|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.
+17612891	6	17	myocarditis	Disease	D009205
+17612891	34	43	clozapine	Chemical	D003024
+17612891	72	83	myocarditis	Disease	D009205
+17612891	120	129	clozapine	Chemical	D003024
+17612891	298	307	clozapine	Chemical	D003024
+17612891	346	359	schizophrenia	Disease	D012559
+17612891	388	399	myocarditis	Disease	D009205
+17612891	422	431	clozapine	Chemical	D003024
+17612891	539	548	clozapine	Chemical	D003024
+17612891	630	644	antidepressant	Chemical	D000928
+17612891	698	709	Myocarditis	Disease	D009205
+17612891	780	789	clozapine	Chemical	D003024
+17612891	861	870	clozapine	Chemical	D003024
+17612891	923	932	psychosis	Disease	D011618
+17612891	1138	1147	clozapine	Chemical	D003024
+17612891	CID	D003024	D009205
+17612891	CID	D000928	D009205
+
+18081909|t|Encephalopathy induced by levetiracetam added to valproate.
+18081909|a|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.
+18081909	0	14	Encephalopathy	Disease	D001927
+18081909	26	39	levetiracetam	Chemical	C026098
+18081909	49	58	valproate	Chemical	D014635
+18081909	108	121	levetiracetam	Chemical	C026098
+18081909	123	126	LEV	Chemical	C026098
+18081909	136	150	encephalopathy	Disease	D001927
+18081909	195	214	idiopathic epilepsy	Disease	C562694
+18081909	232	240	seizures	Disease	D012640
+18081909	258	261	LEV	Chemical	C026098
+18081909	281	290	valproate	Chemical	D014635
+18081909	292	295	VPA	Chemical	D014635
+18081909	333	354	tonic-clonic seizures	Disease	D004830
+18081909	439	498	impaired word fluency, psychomotor speed and working memory	Disease	D008569
+18081909	693	696	LEV	Chemical	C026098
+18081909	747	754	seizure	Disease	D012640
+18081909	CID	C026098	D008569
+18081909	CID	D014635	D008569
+18081909	CID	D014635	D001927
+18081909	CID	C026098	D001927
+18081909	CID	C026098	D004830
+18081909	CID	D014635	D004830
+
+18083142|t|Norepinephrine signaling through beta-adrenergic receptors is critical for expression of cocaine-induced anxiety.
+18083142|a|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.
+18083142	0	14	Norepinephrine	Chemical	D009638
+18083142	89	96	cocaine	Chemical	D003042
+18083142	105	112	anxiety	Disease	D001008
+18083142	126	133	Cocaine	Chemical	D003042
+18083142	250	257	cocaine	Chemical	D003042
+18083142	385	392	cocaine	Chemical	D003042
+18083142	402	409	anxiety	Disease	D001008
+18083142	467	475	dopamine	Chemical	D004298
+18083142	529	543	norepinephrine	Chemical	D009638
+18083142	545	547	NE	Chemical	D009638
+18083142	640	647	cocaine	Chemical	D003042
+18083142	656	663	anxiety	Disease	D001008
+18083142	688	695	cocaine	Chemical	D003042
+18083142	723	730	anxiety	Disease	D001008
+18083142	942	949	cocaine	Chemical	D003042
+18083142	951	958	Cocaine	Chemical	D003042
+18083142	967	974	anxiety	Disease	D001008
+18083142	1039	1049	disulfiram	Chemical	D004221
+18083142	1053	1061	dopamine	Chemical	D004298
+18083142	1222	1233	propranolol	Chemical	D011433
+18083142	1242	1249	cocaine	Chemical	D003042
+18083142	1258	1265	anxiety	Disease	D001008
+18083142	1350	1358	prazosin	Chemical	D011224
+18083142	1387	1396	yohimbine	Chemical	D015016
+18083142	1523	1530	cocaine	Chemical	D003042
+18083142	1539	1546	anxiety	Disease	D001008
+18083142	CID	D003042	D001008
+
+18182964|t|Clonidine for attention-deficit/hyperactivity disorder: II. ECG changes and adverse events analysis.
+18182964|a|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.
+18182964	0	9	Clonidine	Chemical	D003000
+18182964	14	54	attention-deficit/hyperactivity disorder	Disease	D001289
+18182964	154	163	clonidine	Chemical	D003000
+18182964	183	198	methylphenidate	Chemical	D008774
+18182964	216	256	attention-deficit/hyperactivity disorder	Disease	D001289
+18182964	258	262	ADHD	Disease	D001289
+18182964	337	341	ADHD	Disease	D001289
+18182964	368	377	clonidine	Chemical	D003000
+18182964	388	403	methylphenidate	Chemical	D008774
+18182964	414	423	clonidine	Chemical	D003000
+18182964	428	443	methylphenidate	Chemical	D008774
+18182964	525	534	clonidine	Chemical	D003000
+18182964	553	568	methylphenidate	Chemical	D008774
+18182964	757	768	bradycardia	Disease	D001919
+18182964	794	803	clonidine	Chemical	D003000
+18182964	841	850	clonidine	Chemical	D003000
+18182964	1036	1045	clonidine	Chemical	D003000
+18182964	1050	1065	methylphenidate	Chemical	D008774
+18182964	1167	1176	clonidine	Chemical	D003000
+18182964	1272	1282	Drowsiness	Disease	D006970
+18182964	1297	1306	clonidine	Chemical	D003000
+18182964	1361	1370	Clonidine	Chemical	D003000
+18182964	1391	1406	methylphenidate	Chemical	D008774
+18182964	1453	1457	ADHD	Disease	D001289
+18182964	1482	1491	clonidine	Chemical	D003000
+18182964	1511	1522	bradycardia	Disease	D001919
+18182964	1580	1590	drowsiness	Disease	D006970
+18182964	CID	D003000	D001919
+
+18217897|t|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.
+18217897|a|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.
+18217897	0	11	Thalidomide	Chemical	D013792
+18217897	81	102	non-Hodgkin lymphomas	Disease	D008228
+18217897	128	134	Cancer	Disease	D009369
+18217897	139	147	Leukemia	Disease	D007938
+18217897	157	168	Thalidomide	Chemical	D013792
+18217897	228	244	multiple myeloma	Disease	D009101
+18217897	246	266	mantle cell lymphoma	Disease	D020522
+18217897	271	297	lymphoplasmacytic lymphoma	Disease	D008223
+18217897	352	358	tumour	Disease	D009369
+18217897	516	525	lymphomas	Disease	D008223
+18217897	535	546	thalidomide	Chemical	D013792
+18217897	971	987	myelosuppression	Disease	D001855
+18217897	989	996	fatigue	Disease	D005221
+18217897	998	1008	somnolence	Disease	D006970
+18217897	1009	1023	depressed mood	Disease	D003866
+18217897	1025	1035	neuropathy	Disease	D009422
+18217897	1040	1047	dyspnea	Disease	D004417
+18217897	1087	1101	thromboembolic	Disease	D013923
+18217897	1187	1198	thalidomide	Chemical	D013792
+18217897	1211	1220	lymphomas	Disease	D008223
+18217897	1325	1337	lenalidomide	Chemical	C467567
+18217897	CID	D013792	D013923
+
+18996674|t|Intracavernous epinephrine: a minimally invasive treatment for priapism in the emergency department.
+18996674|a|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.
+18996674	15	26	epinephrine	Chemical	D004837
+18996674	63	71	priapism	Disease	D011317
+18996674	101	109	Priapism	Disease	D011317
+18996674	223	230	cocaine	Chemical	D003042
+18996674	324	332	priapism	Disease	D011317
+18996674	339	346	cocaine	Chemical	D003042
+18996674	504	515	epinephrine	Chemical	D004837
+18996674	CID	D003042	D011317
+
+19058010|t|Effect of green tea and vitamin E combination in isoproterenol induced myocardial infarction in rats.
+19058010|a|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.
+19058010	10	19	green tea	Chemical	D010936
+19058010	24	33	vitamin E	Chemical	D014810
+19058010	49	62	isoproterenol	Chemical	D007545
+19058010	71	92	myocardial infarction	Disease	D009203
+19058010	169	178	green tea	Chemical	D010936
+19058010	183	192	vitamin E	Chemical	D014810
+19058010	319	332	isoproterenol	Chemical	D007545
+19058010	334	337	ISO	Chemical	D007545
+19058010	347	368	myocardial infarction	Disease	D009203
+19058010	415	418	ISO	Chemical	D007545
+19058010	573	575	Ca	Chemical	D002118
+19058010	682	684	Na	Chemical	D012964
+19058010	687	688	K	Chemical	D011188
+19058010	701	703	Mg	Chemical	D008274
+19058010	739	748	green tea	Chemical	D010936
+19058010	775	784	vitamin E	Chemical	D014810
+19058010	860	863	ISO	Chemical	D007545
+19058010	988	990	Ca	Chemical	D002118
+19058010	1072	1074	Na	Chemical	D012964
+19058010	1076	1077	K	Chemical	D011188
+19058010	1090	1092	Mg	Chemical	D008274
+19058010	1121	1124	ISO	Chemical	D007545
+19058010	1143	1152	green tea	Chemical	D010936
+19058010	1156	1165	vitamin E	Chemical	D014810
+19058010	1249	1258	green tea	Chemical	D010936
+19058010	1263	1272	vitamin E	Chemical	D014810
+19058010	1280	1283	ISO	Chemical	D007545
+19058010	1292	1313	myocardial infarction	Disease	D009203
+19058010	CID	D007545	D009203
+
+19581773|t|Development of ocular myasthenia during pegylated interferon and ribavirin treatment for chronic hepatitis C.
+19581773|a|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.
+19581773	15	32	ocular myasthenia	Disease	D009157
+19581773	40	60	pegylated interferon	Chemical	C417083
+19581773	65	74	ribavirin	Chemical	D012254
+19581773	89	108	chronic hepatitis C	Disease	D019698
+19581773	148	156	diplopia	Disease	D004172
+19581773	192	227	pegylated interferon (IFN) alpha-2b	Chemical	C417083
+19581773	232	241	ribavirin	Chemical	D012254
+19581773	246	265	chronic hepatitis C	Disease	D019698
+19581773	267	270	CHC	Disease	D019698
+19581773	308	337	ptosis on the right upper lid	Disease	D001763
+19581773	342	371	restricted right eye movement	Disease	D015835
+19581773	500	513	acetylcholine	Chemical	D000109
+19581773	746	768	pegylated IFN alpha-2b	Chemical	C417083
+19581773	773	782	ribavirin	Chemical	D012254
+19581773	788	805	ocular myasthenia	Disease	D009157
+19581773	845	867	pegylated IFN alpha-2b	Chemical	C417083
+19581773	872	881	ribavirin	Chemical	D012254
+19581773	886	889	CHC	Disease	D019698
+19581773	997	1000	IFN	Chemical	C417083
+19581773	CID	D012254	D009157
+19581773	CID	C417083	D001763
+19581773	CID	D012254	D001763
+19581773	CID	C417083	D015835
+19581773	CID	C417083	D009157
+19581773	CID	D012254	D015835
+
+19759529|t|The glycine transporter-1 inhibitor SSR103800 displays a selective and specific antipsychotic-like profile in normal and transgenic mice.
+19759529|a|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.
+19759529	4	11	glycine	Chemical	D005998
+19759529	36	45	SSR103800	Chemical	-1
+19759529	138	151	Schizophrenia	Disease	D012559
+19759529	202	210	dopamine	Chemical	D004298
+19759529	279	288	glutamate	Chemical	D018698
+19759529	289	309	N-methyl-D-aspartate	Chemical	D016202
+19759529	311	315	NMDA	Chemical	D016202
+19759529	334	347	schizophrenic	Disease	D012559
+19759529	448	452	NMDA	Chemical	D016202
+19759529	667	671	NMDA	Chemical	D016202
+19759529	697	704	glycine	Chemical	D005998
+19759529	746	755	SSR103800	Chemical	-1
+19759529	782	786	NMDA	Chemical	D016202
+19759529	823	830	glycine	Chemical	D005998
+19759529	853	857	NMDA	Chemical	D016202
+19759529	972	981	SSR103800	Chemical	-1
+19759529	1020	1033	hyperactivity	Disease	D006948
+19759529	1072	1083	amphetamine	Chemical	D000661
+19759529	1088	1094	MK-801	Chemical	D016291
+19759529	1120	1124	NMDA	Chemical	D016202
+19759529	1172	1181	SSR103800	Chemical	-1
+19759529	1209	1222	hyperactivity	Disease	D006948
+19759529	1254	1258	NMDA	Chemical	D016202
+19759529	1280	1286	MK-801	Chemical	D016291
+19759529	1322	1335	hyperactivity	Disease	D006948
+19759529	1339	1343	NMDA	Chemical	D016202
+19759529	1375	1384	SSR103800	Chemical	-1
+19759529	1402	1415	hyperactivity	Disease	D006948
+19759529	1427	1438	amphetamine	Chemical	D000661
+19759529	1464	1472	dopamine	Chemical	D004298
+19759529	1559	1570	haloperidol	Chemical	D006220
+19759529	1586	1596	olanzapine	Chemical	C076029
+19759529	1598	1607	clozapine	Chemical	D003024
+19759529	1612	1624	aripiprazole	Chemical	C094645
+19759529	1679	1692	hyperactivity	Disease	D006948
+19759529	1724	1733	SSR103800	Chemical	-1
+19759529	1750	1759	catalepsy	Disease	D002375
+19759529	1863	1872	SSR103800	Chemical	-1
+19759529	CID	C094645	D002375
+19759529	CID	D006220	D002375
+19759529	CID	C076029	D002375
+19759529	CID	D016291	D006948
+19759529	CID	D000661	D006948
+19759529	CID	D003024	D002375
+
+19957053|t|Phenylephrine but not ephedrine reduces frontal lobe oxygenation following anesthesia-induced hypotension.
+19957053|a|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.
+19957053	0	13	Phenylephrine	Chemical	D010656
+19957053	22	31	ephedrine	Chemical	D004809
+19957053	32	64	reduces frontal lobe oxygenation	Disease	D002534
+19957053	94	105	hypotension	Disease	D007022
+19957053	177	188	hypotension	Disease	D007022
+19957053	216	229	phenylephrine	Chemical	D010656
+19957053	234	243	ephedrine	Chemical	D004809
+19957053	312	323	hypotension	Disease	D007022
+19957053	371	379	fentanyl	Chemical	D005283
+19957053	401	409	propofol	Chemical	D015742
+19957053	448	461	phenylephrine	Chemical	D010656
+19957053	499	508	ephedrine	Chemical	D004809
+19957053	583	589	stroke	Disease	D020521
+19957053	730	763	a decrease in MAP, HR, SV, and CO	Disease	D007022|D002303	a decrease in MAP|a decrease in CO
+19957053	831	844	phenylephrine	Chemical	D010656
+19957053	1085	1094	ephedrine	Chemical	D004809
+19957053	1276	1289	phenylephrine	Chemical	D010656
+19957053	1301	1312	hypotension	Disease	D007022
+19957053	1375	1384	ephedrine	Chemical	D004809
+19957053	CID	D005283	D007022
+19957053	CID	D005283	D002303
+19957053	CID	D015742	D007022
+19957053	CID	D015742	D002303
+19957053	CID	D010656	D002534
+
+20619828|t|A novel, multiple symptom model of obsessive-compulsive-like behaviors in animals.
+20619828|a|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.
+20619828	35	70	obsessive-compulsive-like behaviors	Disease	D009771
+20619828	120	149	obsessive-compulsive disorder	Disease	D009771
+20619828	151	154	OCD	Disease	D009771
+20619828	260	267	anxiety	Disease	D001008
+20619828	319	322	OCD	Disease	D009771
+20619828	394	408	antidepressant	Chemical	D000928
+20619828	409	421	clomipramine	Chemical	D002997
+20619828	514	526	Clomipramine	Chemical	D002997
+20619828	631	638	anxiety	Disease	D001008
+20619828	680	704	behavioral inflexibility	Disease	-1
+20619828	797	814	memory impairment	Disease	D008569
+20619828	843	851	hoarding	Disease	D060845
+20619828	857	884	corticostriatal dysfunction	Disease	-1
+20619828	886	894	Dopamine	Chemical	D004298
+20619828	947	956	serotonin	Chemical	D012701
+20619828	969	978	serotonin	Chemical	D012701
+20619828	1123	1126	OCD	Disease	D009771
+20619828	1271	1274	OCD	Disease	D009771
+20619828	1296	1299	OCD	Disease	D009771
+20619828	1499	1520	psychiatric disorders	Disease	D001523
+20619828	CID	D002997	D008569
+20619828	CID	D002997	D001008
+20619828	CID	D002997	D060845
+
+891050|t|Late recovery of renal function in a woman with the hemolytic uremic syndrome.
+891050|a|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.
+891050	52	77	hemolytic uremic syndrome	Disease	D006463
+891050	105	130	hemolytic uremic syndrome	Disease	D006463
+891050	132	135	HUS	Disease	D006463
+891050	155	174	oral contraceptives	Chemical	D003276
+891050	197	204	heparin	Chemical	D006493
+891050	206	218	dipyridamole	Chemical	D004176
+891050	343	349	anuria	Disease	D001002
+891050	425	428	HUS	Disease	D006463
+891050	498	506	oliguria	Disease	D009846
+891050	593	596	HUS	Disease	D006463
+891050	704	716	hypertension	Disease	D006973
+891050	721	754	microangiopathic hemolytic anemia	Disease	D000743
+891050	CID	D003276	D006463
+
+983936|t|Effects of acetylsalicylic acid, dipyridamole, and hydrocortisone on epinephrine-induced myocardial injury in dogs.
+983936|a|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.
+983936	11	31	acetylsalicylic acid	Chemical	D001241
+983936	33	45	dipyridamole	Chemical	D004176
+983936	51	65	hydrocortisone	Chemical	D006854
+983936	69	80	epinephrine	Chemical	D004837
+983936	89	106	myocardial injury	Disease	D009202
+983936	159	176	myocardial injury	Disease	D009202
+983936	178	189	epinephrine	Chemical	D004837
+983936	321	342	myocardial infarction	Disease	D009203
+983936	357	368	epinephrine	Chemical	D004837
+983936	423	435	radiocalcium	Chemical	D002132
+983936	723	730	calcium	Chemical	D002118
+983936	827	843	calcium chloride	Chemical	D002122
+983936	870	877	calcium	Chemical	D002118
+983936	929	936	calcium	Chemical	D002118
+983936	984	996	radiocalcium	Chemical	D002132
+983936	1061	1081	acetylsalicylic acid	Chemical	D001241
+983936	1085	1097	dipyridamole	Chemical	D004176
+983936	1106	1120	hydrocortisone	Chemical	D006854
+983936	1138	1149	epinephrine	Chemical	D004837
+983936	1255	1262	calcium	Chemical	D002118
+983936	1543	1563	Acetylsalicylic acid	Chemical	D001241
+983936	1565	1577	dipyridamole	Chemical	D004176
+983936	1583	1597	hydrocortisone	Chemical	D006854
+983936	CID	D004837	D009202
+
+1428568|t|Changes in depressive status associated with topical beta-blockers.
+1428568|a|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.
+1428568	11	21	depressive	Disease	D003866
+1428568	68	78	Depression	Disease	D003866
+1428568	83	101	sexual dysfunction	Disease	D012735
+1428568	270	277	timolol	Chemical	D013999
+1428568	309	318	betaxolol	Chemical	D015784
+1428568	354	366	glaucomatous	Disease	D005901
+1428568	401	408	timolol	Chemical	D013999
+1428568	434	444	depression	Disease	D003866
+1428568	543	553	depression	Disease	D003866
+1428568	700	707	timolol	Chemical	D013999
+1428568	735	745	depression	Disease	D003866
+1428568	856	865	betaxolol	Chemical	D015784
+1428568	885	895	depression	Disease	D003866
+1428568	909	916	timolol	Chemical	D013999
+1428568	CID	D013999	D003866
+
+1720453|t|Long-term follow-up of ifosfamide renal toxicity in children treated for malignant mesenchymal tumors: an International Society of Pediatric Oncology report.
+1720453|a|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.
+1720453	23	33	ifosfamide	Chemical	D007069
+1720453	34	48	renal toxicity	Disease	D007674
+1720453	73	101	malignant mesenchymal tumors	Disease	C535700
+1720453	197	225	malignant mesenchymal tumors	Disease	C535700
+1720453	279	289	ifosfamide	Chemical	D007069
+1720453	357	384	Malignant Mesenchymal Tumor	Disease	C535700
+1720453	509	519	ifosfamide	Chemical	D007069
+1720453	541	582	ifosfamide, vincristine, and dactinomycin	Chemical	C064227
+1720453	584	587	IVA	Chemical	C064227
+1720453	617	626	cisplatin	Chemical	D002945
+1720453	743	748	tumor	Disease	D009369
+1720453	855	865	glucosuria	Disease	D006030
+1720453	867	878	proteinuria	Disease	D011507
+1720453	880	893	aminoaciduria	Disease	D000608
+1720453	919	929	creatinine	Chemical	D003404
+1720453	941	950	phosphate	Chemical	D010710
+1720453	1097	1116	renal abnormalities	Disease	D007674
+1720453	1264	1272	toxicity	Disease	D064420
+1720453	1286	1304	Fanconi's syndrome	Disease	D005198
+1720453	1306	1310	TDFS	Disease	D005198
+1720453	1404	1413	phosphate	Chemical	D010710
+1720453	1503	1511	toxicity	Disease	D064420
+1720453	1573	1583	ifosfamide	Chemical	D007069
+1720453	1666	1671	tumor	Disease	D009369
+1720453	1768	1778	ifosfamide	Chemical	D007069
+1720453	1799	1817	mesenchymal tumors	Disease	C535700
+1720453	CID	D007069	D005198
+1720453	CID	D007069	D007674
+
+1833784|t|Evidence for an involvement of D1 and D2 dopamine receptors in mediating nicotine-induced hyperactivity in rats.
+1833784|a|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.
+1833784	41	49	dopamine	Chemical	D004298
+1833784	73	81	nicotine	Chemical	D009538
+1833784	90	103	hyperactivity	Disease	D006948
+1833784	247	255	nicotine	Chemical	D009538
+1833784	391	399	nicotine	Chemical	D009538
+1833784	447	455	dopamine	Chemical	D004298
+1833784	479	487	nicotine	Chemical	D009538
+1833784	583	591	dopamine	Chemical	D004298
+1833784	636	644	nicotine	Chemical	D009538
+1833784	733	741	Nicotine	Chemical	D009538
+1833784	775	805	increase in locomotor activity	Disease	D006948
+1833784	989	997	nicotine	Chemical	D009538
+1833784	1046	1058	mecamylamine	Chemical	D008464
+1833784	1103	1116	hexamethonium	Chemical	D018738
+1833784	1200	1208	Nicotine	Chemical	D009538
+1833784	1217	1230	hyperactivity	Disease	D006948
+1833784	1274	1283	SCH 23390	Chemical	C534628
+1833784	1313	1323	raclopride	Chemical	D020891
+1833784	1349	1361	fluphenazine	Chemical	D005476
+1833784	1396	1400	PHNO	Chemical	-1
+1833784	1410	1418	nicotine	Chemical	D009538
+1833784	1427	1440	hyperactivity	Disease	D006948
+1833784	1465	1474	SKF 38393	Chemical	D015647
+1833784	1522	1530	nicotine	Chemical	D009538
+1833784	1562	1575	hyperactivity	Disease	D006948
+1833784	1665	1673	nicotine	Chemical	D009538
+1833784	1778	1786	dopamine	Chemical	D004298
+1833784	CID	D009538	D006948
+
+1867351|t|Neuropsychiatric side effects after the use of mefloquine.
+1867351|a|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.
+1867351	47	57	mefloquine	Chemical	D015767
+1867351	143	153	mefloquine	Chemical	D015767
+1867351	185	193	seizures	Disease	D012640
+1867351	201	210	psychoses	Disease	D011605
+1867351	212	228	anxiety neurosis	Disease	D001008
+1867351	240	273	disturbances of sleep-wake rhythm	Disease	D012893
+1867351	483	493	mefloquine	Chemical	D015767
+1867351	719	729	mefloquine	Chemical	D015767
+1867351	815	822	malaria	Disease	D008288
+1867351	854	864	mefloquine	Chemical	D015767
+1867351	CID	D015767	D012893
+1867351	CID	D015767	D011605
+1867351	CID	D015767	D001008
+1867351	CID	D015767	D012640
+
+2070391|t|Reduction in injection pain using buffered lidocaine as a local anesthetic before cardiac catheterization.
+2070391|a|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.
+2070391	23	27	pain	Disease	D010146
+2070391	43	52	lidocaine	Chemical	D008012
+2070391	144	148	pain	Disease	D010146
+2070391	182	191	lidocaine	Chemical	D008012
+2070391	310	319	lidocaine	Chemical	D008012
+2070391	360	364	pain	Disease	D010146
+2070391	526	530	pain	Disease	D010146
+2070391	556	565	lidocaine	Chemical	D008012
+2070391	599	608	lidocaine	Chemical	D008012
+2070391	648	652	pain	Disease	D010146
+2070391	672	681	lidocaine	Chemical	D008012
+2070391	739	748	lidocaine	Chemical	D008012
+2070391	820	829	lidocaine	Chemical	D008012
+2070391	942	946	pain	Disease	D010146
+2070391	CID	D008012	D010146
+
+2266990|t|Randomized, double-blind trial of mazindol in Duchenne dystrophy.
+2266990|a|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.
+2266990	34	42	mazindol	Chemical	D008454
+2266990	46	64	Duchenne dystrophy	Disease	D020388
+2266990	141	149	weakness	Disease	D018908
+2266990	153	171	Duchenne dystrophy	Disease	D020388
+2266990	217	225	mazindol	Chemical	D008454
+2266990	290	308	Duchenne dystrophy	Disease	D020388
+2266990	449	457	mazindol	Chemical	D008454
+2266990	605	613	weakness	Disease	D018908
+2266990	635	643	Mazindol	Chemical	D008454
+2266990	725	733	mazindol	Chemical	D008454
+2266990	743	761	decreased appetite	Disease	D001068
+2266990	769	778	dry mouth	Disease	D014987
+2266990	815	840	gastrointestinal symptoms	Disease	D012817
+2266990	848	856	mazindol	Chemical	D008454
+2266990	910	918	mazindol	Chemical	D008454
+2266990	1054	1062	mazindol	Chemical	D008454
+2266990	1112	1120	mazindol	Chemical	D008454
+2266990	1251	1259	Mazindol	Chemical	D008454
+2266990	1294	1302	weakness	Disease	D018908
+2266990	1306	1324	Duchenne dystrophy	Disease	D020388
+2266990	CID	D008454	D012817
+2266990	CID	D008454	D014987
+2266990	CID	D008454	D001068
+
+2348231|t|Pentoxifylline (Trental) does not inhibit dipyridamole-induced coronary hyperemia: implications for dipyridamole-thallium-201 myocardial imaging.
+2348231|a|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.
+2348231	0	14	Pentoxifylline	Chemical	D010431
+2348231	16	23	Trental	Chemical	D010431
+2348231	42	54	dipyridamole	Chemical	D004176
+2348231	72	81	hyperemia	Disease	D006940
+2348231	100	112	dipyridamole	Chemical	D004176
+2348231	113	121	thallium	Chemical	D013793
+2348231	146	158	Dipyridamole	Chemical	D004176
+2348231	159	167	thallium	Chemical	D013793
+2348231	241	268	peripheral vascular disease	Disease	D016491
+2348231	304	318	pentoxifylline	Chemical	D010431
+2348231	320	327	Trental	Chemical	D010431
+2348231	332	346	methylxanthine	Chemical	C008514
+2348231	376	401	intermittent claudication	Disease	D007383
+2348231	411	425	pentoxifylline	Chemical	D010431
+2348231	435	447	dipyridamole	Chemical	D004176
+2348231	465	474	hyperemia	Disease	D006940
+2348231	486	501	methylxanthines	Chemical	C008514
+2348231	510	522	theophylline	Chemical	D013806
+2348231	554	566	dipyridamole	Chemical	D004176
+2348231	567	575	thallium	Chemical	D013793
+2348231	648	660	dipyridamole	Chemical	D004176
+2348231	730	744	pentoxifylline	Chemical	D010431
+2348231	775	787	theophylline	Chemical	D013806
+2348231	898	910	Dipyridamole	Chemical	D004176
+2348231	993	1007	pentoxifylline	Chemical	D010431
+2348231	1045	1059	pentoxifylline	Chemical	D010431
+2348231	1088	1100	dipyridamole	Chemical	D004176
+2348231	1109	1118	hyperemia	Disease	D006940
+2348231	1181	1193	theophylline	Chemical	D013806
+2348231	1231	1246	pentoxyifylline	Chemical	D010431
+2348231	1264	1276	dipyridamole	Chemical	D004176
+2348231	1294	1303	hyperemia	Disease	D006940
+2348231	CID	D004176	D006940
+2348231	CID	D010431	D007383
+
+2355241|t|Cause of death among patients with Parkinson's disease: a rare mortality due to cerebral haemorrhage.
+2355241|a|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.
+2355241	9	14	death	Disease	D003643
+2355241	35	54	Parkinson's disease	Disease	D010300
+2355241	80	100	cerebral haemorrhage	Disease	D002543
+2355241	112	117	death	Disease	D003643
+2355241	145	165	cerebral haemorrhage	Disease	D002543
+2355241	215	234	Parkinson's disease	Disease	D010300
+2355241	355	360	death	Disease	D003643
+2355241	366	375	pneumonia	Disease	D011014
+2355241	380	390	bronchitis	Disease	D001991
+2355241	410	419	neoplasms	Disease	D009369
+2355241	429	443	heart diseases	Disease	D006331
+2355241	452	471	cerebral infarction	Disease	D002544
+2355241	483	494	septicaemia	Disease	D018805
+2355241	503	523	Cerebral haemorrhage	Disease	D002543
+2355241	560	565	death	Disease	D003643
+2355241	595	601	deaths	Disease	D003643
+2355241	666	671	death	Disease	D003643
+2355241	740	760	cerebral haemorrhage	Disease	D002543
+2355241	775	780	death	Disease	D003643
+2355241	798	817	Parkinson's disease	Disease	D010300
+2355241	834	845	hypotensive	Disease	D007022
+2355241	856	864	levodopa	Chemical	D007980
+2355241	871	882	hypotensive	Disease	D007022
+2355241	908	921	noradrenaline	Chemical	D009638
+2355241	936	948	parkinsonian	Disease	D010300
+2355241	CID	D007980	D007022
+
+2445283|t|Tolerance and antiviral effect of ribavirin in patients with Argentine hemorrhagic fever.
+2445283|a|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.
+2445283	34	43	ribavirin	Chemical	D012254
+2445283	61	88	Argentine hemorrhagic fever	Disease	D006478
+2445283	124	133	ribavirin	Chemical	D012254
+2445283	165	192	Argentine hemorrhagic fever	Disease	D006478
+2445283	194	197	AHF	Disease	D006478
+2445283	251	260	ribavirin	Chemical	D012254
+2445283	293	300	viremia	Disease	D014766
+2445283	365	370	death	Disease	D003643
+2445283	397	403	anemia	Disease	D000740
+2445283	479	488	ribavirin	Chemical	D012254
+2445283	534	537	AHF	Disease	D006478
+2445283	548	554	anemia	Disease	D000740
+2445283	651	660	ribavirin	Chemical	D012254
+2445283	688	691	AHF	Disease	D006478
+2445283	CID	D012254	D000740
+
+2950248|t|Dipyridamole-induced myocardial ischemia.
+2950248|a|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.
+2950248	0	12	Dipyridamole	Chemical	D004176
+2950248	21	40	myocardial ischemia	Disease	D017202
+2950248	42	48	Angina	Disease	D000787
+2950248	129	141	dipyridamole	Chemical	D004176
+2950248	305	317	dipyridamole	Chemical	D004176
+2950248	336	348	dipyridamole	Chemical	D004176
+2950248	357	376	myocardial ischemia	Disease	D017202
+2950248	435	458	coronary artery disease	Disease	D003324
+2950248	597	609	dipyridamole	Chemical	D004176
+2950248	618	626	ischemia	Disease	D007511
+2950248	CID	D004176	D000787
+
+3015567|t|Inhibition of immunoreactive corticotropin-releasing factor secretion into the hypophysial-portal circulation by delayed glucocorticoid feedback.
+3015567|a|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.
+3015567	146	159	Nitroprusside	Chemical	D009599
+3015567	168	179	hypotension	Disease	D007022
+3015567	390	410	arginine vasopressin	Chemical	D001127
+3015567	415	423	oxytocin	Chemical	D010121
+3015567	540	554	corticosterone	Chemical	D003345
+3015567	567	575	urethane	Chemical	D014520
+3015567	699	719	arginine vasopressin	Chemical	D001127
+3015567	724	732	oxytocin	Chemical	D010121
+3015567	740	754	corticosterone	Chemical	D003345
+3015567	833	847	corticosterone	Chemical	D003345
+3015567	890	904	corticosterone	Chemical	D003345
+3015567	979	992	nitroprusside	Chemical	D009599
+3015567	1001	1012	hypotension	Disease	D007022
+3015567	1048	1062	corticosterone	Chemical	D003345
+3015567	CID	D009599	D007022
+
+3031535|t|Noradrenergic involvement in catalepsy induced by delta 9-tetrahydrocannabinol.
+3031535|a|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.
+3031535	29	38	catalepsy	Disease	D002375
+3031535	50	78	delta 9-tetrahydrocannabinol	Chemical	D013759
+3031535	175	203	delta 9-tetrahydrocannabinol	Chemical	D013759
+3031535	205	208	THC	Chemical	D013759
+3031535	243	260	6-hydroxydopamine	Chemical	D016627
+3031535	262	268	6-OHDA	Chemical	D016627
+3031535	278	289	desipramine	Chemical	D003891
+3031535	294	300	6-OHDA	Chemical	D016627
+3031535	392	395	THC	Chemical	D013759
+3031535	443	449	6-OHDA	Chemical	D016627
+3031535	527	538	desipramine	Chemical	D003891
+3031535	543	549	6-OHDA	Chemical	D016627
+3031535	628	639	haloperidol	Chemical	D006220
+3031535	687	698	desipramine	Chemical	D003891
+3031535	703	709	6-OHDA	Chemical	D016627
+3031535	739	745	6-OHDA	Chemical	D016627
+3031535	891	900	catalepsy	Disease	D002375
+3031535	912	915	THC	Chemical	D013759
+3031535	963	972	catalepsy	Disease	D002375
+3031535	984	995	haloperidol	Chemical	D006220
+3031535	CID	D006220	D002375
+3031535	CID	D013759	D002375
+
+3125768|t|Intracranial pressure increases during alfentanil-induced rigidity.
+3125768|a|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.
+3125768	39	49	alfentanil	Chemical	D015760
+3125768	58	66	rigidity	Disease	D009127
+3125768	116	126	alfentanil	Chemical	D015760
+3125768	135	143	rigidity	Disease	D009127
+3125768	235	244	halothane	Chemical	D006221
+3125768	385	394	halothane	Chemical	D006221
+3125768	416	426	alfentanil	Chemical	D015760
+3125768	477	486	halothane	Chemical	D006221
+3125768	531	547	somatic rigidity	Disease	D009127
+3125768	700	708	rigidity	Disease	D009127
+3125768	728	738	metocurine	Chemical	C032943
+3125768	817	827	alfentanil	Chemical	D015760
+3125768	861	869	rigidity	Disease	D009127
+3125768	895	905	alfentanil	Chemical	D015760
+3125768	CID	D015760	D009127
+
+3187073|t|Adverse cardiac effects during induction chemotherapy treatment with cis-platin and 5-fluorouracil.
+3187073|a|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.
+3187073	69	79	cis-platin	Chemical	D002945
+3187073	84	98	5-fluorouracil	Chemical	D005472
+3187073	136	159	head and neck carcinoma	Disease	D006258
+3187073	164	184	esophageal carcinoma	Disease	D004938
+3187073	304	314	cis-platin	Chemical	D002945
+3187073	337	341	5-FU	Chemical	D005472
+3187073	727	749	cardiovascular disease	Disease	D002318
+3187073	957	971	cardiotoxicity	Disease	D066126
+3187073	1013	1035	cardiovascular disease	Disease	D002318
+3187073	1116	1130	cardiotoxicity	Disease	D066126
+3187073	1136	1146	chest pain	Disease	D002637
+3187073	1170	1189	atrial fibrillation	Disease	D001281
+3187073	1212	1236	ventricular fibrillation	Disease	D014693
+3187073	1256	1268	sudden death	Disease	D003645
+3187073	1314	1318	5-FU	Chemical	D005472
+3187073	1412	1422	chest pain	Disease	D002637
+3187073	1426	1441	tachyarrhythmia	Disease	D013610
+3187073	CID	D002945	D002318
+3187073	CID	D005472	D014693
+3187073	CID	D005472	D002637
+3187073	CID	D005472	D001281
+3187073	CID	D002945	D001281
+3187073	CID	D005472	D002318
+3187073	CID	D002945	D014693
+3187073	CID	D002945	D002637
+
+3371379|t|Verapamil-induced carbamazepine neurotoxicity. A report of two cases.
+3371379|a|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).
+3371379	0	9	Verapamil	Chemical	D014700
+3371379	18	31	carbamazepine	Chemical	D002220
+3371379	32	45	neurotoxicity	Disease	D020258
+3371379	97	110	carbamazepine	Chemical	D002220
+3371379	111	124	neurotoxicity	Disease	D020258
+3371379	155	164	verapamil	Chemical	D014700
+3371379	219	226	calcium	Chemical	D002118
+3371379	249	258	verapamil	Chemical	D014700
+3371379	279	292	carbamazepine	Chemical	D002220
+3371379	372	385	carbamazepine	Chemical	D002220
+3371379	417	430	carbamazepine	Chemical	D002220
+3371379	CID	D014700	D020258
+3371379	CID	D002220	D020258
+
+3503576|t|Serial studies of auditory neurotoxicity in patients receiving deferoxamine therapy.
+3503576|a|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.
+3503576	18	40	auditory neurotoxicity	Disease	D006311
+3503576	63	75	deferoxamine	Chemical	D003676
+3503576	85	118	Visual and auditory neurotoxicity	Disease	D014786|D006311	Visual neurotoxicity|auditory neurotoxicity
+3503576	193	199	anemia	Disease	D000740
+3503576	219	223	iron	Chemical	D007501
+3503576	266	278	deferoxamine	Chemical	D003676
+3503576	326	415	abnormal audiograms with deficits mostly in the high frequency range of 4,000 to 8,000 Hz	Disease	D006316
+3503576	480	492	deferoxamine	Chemical	D003676
+3503576	796	816	permanent disability	Disease	D003638
+3503576	871	883	deferoxamine	Chemical	D003676
+3503576	1048	1068	auditory abnormality	Disease	D006311
+3503576	1117	1125	toxicity	Disease	D064420
+3503576	1257	1269	deferoxamine	Chemical	D003676
+3503576	1354	1366	deferoxamine	Chemical	D003676
+3503576	1386	1397	ototoxicity	Disease	D006311
+3503576	1504	1516	deferoxamine	Chemical	D003676
+3503576	1604	1612	toxicity	Disease	D064420
+3503576	1780	1792	deferoxamine	Chemical	D003676
+3503576	1865	1877	hearing loss	Disease	D034381
+3503576	2195	2215	auditory dysfunction	Disease	D006311
+3503576	CID	D003676	D006316
+3503576	CID	D003676	D014786
+
+3560095|t|Flurbiprofen in the treatment of juvenile rheumatoid arthritis.
+3560095|a|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.
+3560095	0	12	Flurbiprofen	Chemical	D005480
+3560095	33	62	juvenile rheumatoid arthritis	Disease	D001171
+3560095	90	119	juvenile rheumatoid arthritis	Disease	D001171
+3560095	143	155	flurbiprofen	Chemical	D005480
+3560095	249	258	arthritis	Disease	D001168
+3560095	336	349	tender joints	Disease	-1
+3560095	367	375	swelling	Disease	D004487
+3560095	380	390	tenderness	Disease	-1
+3560095	434	451	morning stiffness	Disease	-1
+3560095	537	555	fecal occult blood	Disease	-1
+3560095	615	645	gastrointestinal (GI) bleeding	Disease	D006471
+3560095	732	740	headache	Disease	D006261
+3560095	745	759	abdominal pain	Disease	D015746
+3560095	CID	D005480	D006261
+3560095	CID	D005480	D006471
+3560095	CID	D005480	D015746
+
+3714122|t|The correlation between neurotoxic esterase inhibition and mipafox-induced neuropathic damage in rats.
+3714122|a|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.
+3714122	24	34	neurotoxic	Disease	D020258
+3714122	59	66	mipafox	Chemical	C005238
+3714122	75	93	neuropathic damage	Disease	D009422
+3714122	127	145	neuropathic damage	Disease	D009422
+3714122	164	174	neurotoxic	Disease	D020258
+3714122	187	197	neuropathy	Disease	D009422
+3714122	258	265	Mipafox	Chemical	C005238
+3714122	267	310	N, N'-diisopropylphosphorodiamidofluoridate	Chemical	C005238
+3714122	315	325	neurotoxic	Disease	D020258
+3714122	326	341	organophosphate	Chemical	D010755
+3714122	459	466	Mipafox	Chemical	C005238
+3714122	548	559	cord damage	Disease	D013118
+3714122	939	946	Mipafox	Chemical	C005238
+3714122	1114	1125	cord damage	Disease	D013118
+3714122	1265	1272	Mipafox	Chemical	C005238
+3714122	1294	1312	neuropathic damage	Disease	D009422
+3714122	CID	C005238	D013118
+
+3828020|t|Cerebral infarction with a single oral dose of phenylpropanolamine.
+3828020|a|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.
+3828020	0	19	Cerebral infarction	Disease	D002544
+3828020	47	66	phenylpropanolamine	Chemical	D010665
+3828020	68	87	Phenylpropanolamine	Chemical	D010665
+3828020	89	92	PPA	Chemical	D010665
+3828020	155	166	amphetamine	Chemical	D000661
+3828020	309	317	seizures	Disease	D012640
+3828020	319	343	intracerebral hemorrhage	Disease	D002543
+3828020	345	370	neuropsychiatric symptoms	Disease	D001523
+3828020	391	410	cerebral infarction	Disease	D002544
+3828020	463	482	cerebral infarction	Disease	D002544
+3828020	518	521	PPA	Chemical	D010665
+3828020	CID	D010665	D001523
+3828020	CID	D010665	D012640
+3828020	CID	D010665	D002544
+3828020	CID	D010665	D002543
+
+4812392|t|Treatment of psoriasis with azathioprine.
+4812392|a|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.
+4812392	13	22	psoriasis	Disease	D011565
+4812392	28	40	azathioprine	Chemical	D001379
+4812392	42	54	Azathioprine	Chemical	D001379
+4812392	125	134	psoriasis	Disease	D011565
+4812392	259	270	cholestasis	Disease	D002779
+4812392	304	312	fibrosis	Disease	D005355
+4812392	406	418	azathioprine	Chemical	D001379
+4812392	459	471	liver damage	Disease	D056486
+4812392	CID	D001379	D005355
+4812392	CID	D001379	D002779
+
+6518066|t|Maternal lithium and neonatal Ebstein's anomaly: evaluation with cross-sectional echocardiography.
+6518066|a|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.
+6518066	9	16	lithium	Chemical	D008094
+6518066	30	47	Ebstein's anomaly	Disease	D004437
+6518066	189	196	lithium	Chemical	D008094
+6518066	230	247	Ebstein's anomaly	Disease	D004437
+6518066	390	407	Ebstein's anomaly	Disease	D004437
+6518066	476	483	lithium	Chemical	D008094
+6518066	583	590	lithium	Chemical	D008094
+6518066	599	620	cardiac malformations	Disease	D006331
+6518066	CID	D008094	D004437
+
+6534871|t|Effects of training on the extent of experimental myocardial infarction in aging rats.
+6534871|a|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.
+6534871	50	71	myocardial infarction	Disease	D009203
+6534871	130	143	isoproterenol	Chemical	D007545
+6534871	152	173	myocardial infarction	Disease	D009203
+6534871	343	351	infarcts	Disease	D007238
+6534871	458	472	isoproterenols	Chemical	D007545
+6534871	738	759	myocardial infarction	Disease	D009203
+6534871	CID	D007545	D009203
+
+6538499|t|Effect of polyethylene glycol 400 on adriamycin toxicity in mice.
+6538499|a|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.
+6538499	10	33	polyethylene glycol 400	Chemical	D011092
+6538499	37	47	adriamycin	Chemical	D004317
+6538499	48	56	toxicity	Disease	D064420
+6538499	111	134	polyethylene glycol 400	Chemical	D011092
+6538499	136	143	PEG 400	Chemical	D011092
+6538499	204	214	adriamycin	Chemical	D004317
+6538499	216	219	ADR	Chemical	D004317
+6538499	244	251	PEG 400	Chemical	D011092
+6538499	317	320	ADR	Chemical	D004317
+6538499	410	413	ADR	Chemical	D004317
+6538499	422	455	cardiac morphological alterations	Disease	D009202
+6538499	493	496	ADR	Chemical	D004317
+6538499	519	533	L1210 leukemia	Disease	D007939
+6538499	541	562	Ehrlich ascites tumor	Disease	D002286
+6538499	CID	D004317	D009202
+
+6747681|t|Intra-arterial BCNU chemotherapy for treatment of malignant gliomas of the central nervous system.
+6747681|a|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.
+6747681	15	19	BCNU	Chemical	D002330
+6747681	50	67	malignant gliomas	Disease	D005910
+6747681	142	146	BCNU	Chemical	D002330
+6747681	148	185	1,3-bis-(2-chloroethyl)-1-nitrosourea	Chemical	D002330
+6747681	310	327	malignant gliomas	Disease	D005910
+6747681	367	371	BCNU	Chemical	D002330
+6747681	634	646	astrocytomas	Disease	D001254
+6747681	691	696	tumor	Disease	D009369
+6747681	808	813	tumor	Disease	D009369
+6747681	835	840	edema	Disease	D004487
+6747681	1220	1232	astrocytomas	Disease	D001254
+6747681	1334	1338	BCNU	Chemical	D002330
+6747681	1545	1549	BCNU	Chemical	D002330
+6747681	1611	1625	loss of vision	Disease	D014786
+6747681	1641	1659	retinal vasculitis	Disease	D031300
+6747681	1678	1689	visual loss	Disease	D014786
+6747681	1731	1738	ethanol	Chemical	D000431
+6747681	CID	D002330	D031300
+
+6861444|t|Blood pressure response to chronic low-dose intrarenal noradrenaline infusion in conscious rats.
+6861444|a|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.
+6861444	55	68	noradrenaline	Chemical	D009638
+6861444	97	112	Sodium chloride	Chemical	D012965
+6861444	132	145	noradrenaline	Chemical	D009638
+6861444	346	359	noradrenaline	Chemical	D009638
+6861444	367	379	hypertension	Disease	D006973
+6861444	486	499	noradrenaline	Chemical	D009638
+6861444	521	534	noradrenaline	Chemical	D009638
+6861444	576	589	noradrenaline	Chemical	D009638
+6861444	653	666	noradrenaline	Chemical	D009638
+6861444	702	714	hypertension	Disease	D006973
+6861444	740	753	noradrenaline	Chemical	D009638
+6861444	818	831	noradrenaline	Chemical	D009638
+6861444	CID	D009638	D006973
+
+7053303|t|Age and renal clearance of cimetidine.
+7053303|a|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.
+7053303	27	37	cimetidine	Chemical	D002927
+7053303	83	93	cimetidine	Chemical	D002927
+7053303	195	205	cimetidine	Chemical	D002927
+7053303	253	263	creatinine	Chemical	D003404
+7053303	265	275	Cimetidine	Chemical	D002927
+7053303	351	361	cimetidine	Chemical	D002927
+7053303	395	405	cimetidine	Chemical	D002927
+7053303	456	466	cimetidine	Chemical	D002927
+7053303	480	490	creatinine	Chemical	D003404
+7053303	565	575	cimetidine	Chemical	D002927
+7053303	665	675	cimetidine	Chemical	D002927
+7053303	706	716	cimetidine	Chemical	D002927
+7053303	768	776	dementia	Disease	D003704
+7053303	793	803	cimetidine	Chemical	D002927
+7053303	896	919	liver or kidney disease	Disease	D008107|D007674	liver disease|kidney disease
+7053303	928	938	cimetidine	Chemical	D002927
+7053303	982	992	cimetidine	Chemical	D002927
+7053303	1027	1035	dementia	Disease	D003704
+7053303	CID	D002927	D003704
+
+7088431|t|Development of clear cell adenocarcinoma in DES-exposed offspring under observation.
+7088431|a|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.
+7088431	15	40	clear cell adenocarcinoma	Disease	D018262
+7088431	44	47	DES	Chemical	D004054
+7088431	98	137	clear cell adenocarcinoma of the vagina	Disease	D018262|D014625	clear cell adenocarcinoma|adenocarcinoma of the vagina
+7088431	195	213	diethylstilbestrol	Chemical	D004054
+7088431	287	296	carcinoma	Disease	D002277
+7088431	445	454	carcinoma	Disease	D002277
+7088431	CID	D004054	D014625
+7088431	CID	D004054	D018262
+
+7248170|t|Phenobarbitone-induced enlargement of the liver in the rat: its relationship to carbon tetrachloride-induced cirrhosis.
+7248170|a|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.
+7248170	0	14	Phenobarbitone	Chemical	D010634
+7248170	23	47	enlargement of the liver	Disease	D006529
+7248170	80	100	carbon tetrachloride	Chemical	D002251
+7248170	109	118	cirrhosis	Disease	D005355
+7248170	140	162	cirrhosis of the liver	Disease	D008103
+7248170	236	243	ascites	Disease	D001201
+7248170	299	311	splenomegaly	Disease	D013163
+7248170	345	352	atrophy	Disease	D001284
+7248170	405	425	carbon tetrachloride	Chemical	D002251
+7248170	456	470	phenobarbitone	Chemical	D010634
+7248170	556	576	carbon tetrachloride	Chemical	D002251
+7248170	596	610	phenobarbitone	Chemical	D010634
+7248170	619	643	enlargement of the liver	Disease	D006529
+7248170	699	703	CCl4	Chemical	D002251
+7248170	775	789	phenobarbitone	Chemical	D010634
+7248170	985	1005	carbon tetrachloride	Chemical	D002251
+7248170	1027	1041	phenobarbitone	Chemical	D010634
+7248170	CID	D010634	D008103
+7248170	CID	D002251	D008103
+7248170	CID	D010634	D006529
+
+7453952|t|Attenuation of the lithium-induced diabetes-insipidus-like syndrome by amiloride in rats.
+7453952|a|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.
+7453952	19	26	lithium	Chemical	D008094
+7453952	35	67	diabetes-insipidus-like syndrome	Disease	D003919
+7453952	71	80	amiloride	Chemical	D000584
+7453952	104	113	amiloride	Chemical	D000584
+7453952	117	124	lithium	Chemical	D008094
+7453952	133	143	polydipsia	Disease	D059606
+7453952	148	156	polyuria	Disease	D011141
+7453952	168	175	lithium	Chemical	D008094
+7453952	299	303	LiCl	Chemical	D018021
+7453952	305	314	Amiloride	Chemical	D000584
+7453952	453	462	amiloride	Chemical	D000584
+7453952	496	503	lithium	Chemical	D008094
+7453952	623	630	lithium	Chemical	D008094
+7453952	715	722	lithium	Chemical	D008094
+7453952	818	825	lithium	Chemical	D008094
+7453952	834	866	diabetes-insipidus-like syndrome	Disease	D003919
+7453952	870	879	amiloride	Chemical	D000584
+7453952	936	943	lithium	Chemical	D008094
+7453952	1038	1047	potassium	Chemical	D011188
+7453952	1082	1091	amiloride	Chemical	D000584
+7453952	1110	1117	lithium	Chemical	D008094
+7453952	1150	1160	polydipsia	Disease	D059606
+7453952	1165	1173	polyuria	Disease	D011141
+7453952	1217	1226	amiloride	Chemical	D000584
+7453952	1268	1275	lithium	Chemical	D008094
+7453952	CID	D008094	D003919
+
+7802851|t|Safety and side-effects of alprazolam. Controlled study in agoraphobia with panic disorder.
+7802851|a|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.
+7802851	27	37	alprazolam	Chemical	D000525
+7802851	59	70	agoraphobia	Disease	D000379
+7802851	76	90	panic disorder	Disease	D016584
+7802851	126	141	benzodiazepines	Chemical	D001569
+7802851	219	229	alprazolam	Chemical	D000525
+7802851	245	259	panic disorder	Disease	D016584
+7802851	265	276	agoraphobia	Disease	D000379
+7802851	433	447	panic disorder	Disease	D016584
+7802851	453	464	agoraphobia	Disease	D000379
+7802851	484	494	alprazolam	Chemical	D000525
+7802851	667	677	alprazolam	Chemical	D000525
+7802851	731	741	alprazolam	Chemical	D000525
+7802851	799	809	depression	Disease	D003866
+7802851	811	819	enuresis	Disease	D004775
+7802851	839	849	aggression	Disease	D001523
+7802851	897	909	irritability	Disease	D001523
+7802851	911	926	impaired memory	Disease	D008569
+7802851	928	939	weight loss	Disease	D015431
+7802851	944	950	ataxia	Disease	D001259
+7802851	1091	1101	Alprazolam	Chemical	D000525
+7802851	CID	D000525	D001259
+7802851	CID	D000525	D008569
+7802851	CID	D000525	D004775
+7802851	CID	D000525	D003866
+7802851	CID	D000525	D015431
+
+8319760|t|Dup 753 prevents the development of puromycin aminonucleoside-induced nephrosis.
+8319760|a|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.
+8319760	0	7	Dup 753	Chemical	D019808
+8319760	36	61	puromycin aminonucleoside	Chemical	D011692
+8319760	70	79	nephrosis	Disease	D009401
+8319760	99	118	nephrotic syndromes	Disease	D009404
+8319760	127	138	proteinuria	Disease	D011507
+8319760	140	155	hypoalbuminemia	Disease	D034141
+8319760	157	177	hypercholesterolemia	Disease	D006937
+8319760	194	213	blood nitrogen urea	Chemical	D001806
+8319760	247	272	puromycin aminonucleoside	Chemical	D011692
+8319760	322	329	Dup 753	Chemical	D019808
+8319760	331	339	losartan	Chemical	D019808
+8319760	350	364	angiotensin II	Chemical	D000804
+8319760	477	488	angiotensin	Chemical	D000809
+8319760	518	543	puromycin aminonucleoside	Chemical	D011692
+8319760	552	561	nephrosis	Disease	D009401
+8319760	CID	D011692	D006937
+8319760	CID	D011692	D011507
+8319760	CID	D011692	D009404
+8319760	CID	D011692	D034141
+
+8386779|t|Sodium bicarbonate alleviates penile pain induced by intracavernous injections for erectile dysfunction.
+8386779|a|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.
+8386779	0	18	Sodium bicarbonate	Chemical	D017693
+8386779	30	41	penile pain	Disease	D004414
+8386779	83	103	erectile dysfunction	Disease	D007172
+8386779	140	151	penile pain	Disease	D004414
+8386779	300	311	penile pain	Disease	D004414
+8386779	380	398	sodium bicarbonate	Chemical	D017693
+8386779	502	511	impotence	Disease	D007172
+8386779	564	574	papaverine	Chemical	D010208
+8386779	592	604	phentolamine	Chemical	D010646
+8386779	624	640	prostaglandin E1	Chemical	D000527
+8386779	693	711	sodium bicarbonate	Chemical	D017693
+8386779	752	770	sodium bicarbonate	Chemical	D017693
+8386779	818	829	penile pain	Disease	D004414
+8386779	898	916	sodium bicarbonate	Chemical	D017693
+8386779	931	942	penile pain	Disease	D004414
+8386779	981	992	penile pain	Disease	D004414
+8386779	CID	D010646	D004414
+8386779	CID	D000527	D004414
+
+8421099|t|Prospective study of the long-term effects of somatostatin analog (octreotide) on gallbladder function and gallstone formation in Chinese acromegalic patients.
+8421099|a|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.
+8421099	67	77	octreotide	Chemical	D015282
+8421099	107	116	gallstone	Disease	D042882
+8421099	138	149	acromegalic	Disease	D000172
+8421099	280	290	acromegaly	Disease	D000172
+8421099	344	354	octreotide	Chemical	D015282
+8421099	451	461	octreotide	Chemical	D015282
+8421099	500	510	gallstones	Disease	D042882
+8421099	528	547	acute cholecystitis	Disease	D041881
+8421099	759	768	depressed	Disease	D003866
+8421099	809	819	octreotide	Chemical	D015282
+8421099	843	853	gallstones	Disease	D042882
+8421099	986	996	gallstones	Disease	D042882
+8421099	1141	1150	depressed	Disease	D003866
+8421099	1327	1337	gallstones	Disease	D042882
+8421099	1343	1356	cholecystitis	Disease	D002764
+8421099	1364	1374	octreotide	Chemical	D015282
+8421099	1394	1405	acromegalic	Disease	D000172
+8421099	1510	1520	octreotide	Chemical	D015282
+8421099	1532	1543	acromegalic	Disease	D000172
+8421099	CID	D015282	D041881
+8421099	CID	D015282	D042882
+
+8649546|t|Improvement of levodopa-induced dyskinesia by propranolol in Parkinson's disease.
+8649546|a|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.
+8649546	15	23	levodopa	Chemical	D007980
+8649546	32	42	dyskinesia	Disease	D004409
+8649546	46	57	propranolol	Chemical	D011433
+8649546	61	80	Parkinson's disease	Disease	D010300
+8649546	112	131	Parkinson's disease	Disease	D010300
+8649546	133	135	PD	Disease	D010300
+8649546	161	171	dyskinesia	Disease	D004409
+8649546	190	201	propranolol	Chemical	D011433
+8649546	304	314	dyskinesia	Disease	D004409
+8649546	341	353	parkinsonian	Disease	D010300
+8649546	354	370	motor disability	Disease	D009069
+8649546	394	404	dyskinesia	Disease	D004409
+8649546	440	448	dystonia	Disease	D004421
+8649546	540	548	levodopa	Chemical	D007980
+8649546	579	589	dyskinesia	Disease	D004409
+8649546	593	595	PD	Disease	D010300
+8649546	CID	D007980	D004409
+
+8919272|t|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.
+8919272|a|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.
+8919272	26	40	encephalopathy	Disease	D001927
+8919272	96	105	valproate	Chemical	D014635
+8919272	259	275	sodium valproate	Chemical	D014635
+8919272	391	413	neurological disorders	Disease	D009422
+8919272	425	442	cerebellum damage	Disease	D002526
+8919272	445	454	valproate	Chemical	D014635
+8919272	455	469	encephalopathy	Disease	D001927
+8919272	837	845	necrosis	Disease	D009336
+8919272	1136	1143	luminal	Chemical	D010634
+8919272	1281	1289	necrotic	Disease	D009336
+8919272	1871	1878	luminal	Chemical	D010634
+8919272	1988	2002	hepatic damage	Disease	D056486
+8919272	2011	2025	hyperammonemia	Disease	D022124
+8919272	2051	2060	valproate	Chemical	D014635
+8919272	2061	2075	encephalopathy	Disease	D001927
+8919272	CID	D014635	D001927
+
+9199746|t|Macula toxicity after intravitreal amikacin.
+9199746|a|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.
+9199746	7	15	toxicity	Disease	D064420
+9199746	35	43	amikacin	Chemical	D000583
+9199746	79	94	aminoglycosides	Chemical	D000617
+9199746	143	158	endophthalmitis	Disease	D009877
+9199746	168	178	infarction	Disease	D007238
+9199746	251	259	amikacin	Chemical	D000583
+9199746	260	276	retinal toxicity	Disease	D012164
+9199746	302	310	amikacin	Chemical	D000583
+9199746	315	325	vancomycin	Chemical	D014640
+9199746	347	376	streptococcal endophthalmitis	Disease	D013290
+9199746	387	402	Endophthalmitis	Disease	D009877
+9199746	478	489	fluorescein	Chemical	D019793
+9199746	542	556	telangiectasis	Disease	D013684
+9199746	633	649	retinal toxicity	Disease	D012164
+9199746	662	671	ischaemia	Disease	D007511
+9199746	712	728	retinal toxicity	Disease	D012164
+9199746	CID	D000583	D007511
+9199746	CID	D000583	D012164
+
+9249847|t|Iatrogenically induced intractable atrioventricular reentrant tachycardia after verapamil and catheter ablation in a patient with Wolff-Parkinson-White syndrome and idiopathic dilated cardiomyopathy.
+9249847|a|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.
+9249847	35	73	atrioventricular reentrant tachycardia	Disease	D013611
+9249847	80	89	verapamil	Chemical	D014700
+9249847	130	160	Wolff-Parkinson-White syndrome	Disease	D014927
+9249847	165	198	idiopathic dilated cardiomyopathy	Disease	D002311
+9249847	218	230	WPW syndrome	Disease	D014927
+9249847	235	268	idiopathic dilated cardiomyopathy	Disease	D002311
+9249847	282	320	atrioventricular reentrant tachycardia	Disease	D013611
+9249847	322	326	AVRT	Disease	D013611
+9249847	423	432	verapamil	Chemical	D014700
+9249847	534	538	AVRT	Disease	D013611
+9249847	CID	D014700	D013611
+
+9284778|t|Epidemic of liver disease caused by hydrochlorofluorocarbons used as ozone-sparing substitutes of chlorofluorocarbons.
+9284778|a|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.
+9284778	12	25	liver disease	Disease	D008107
+9284778	36	60	hydrochlorofluorocarbons	Chemical	-1
+9284778	69	74	ozone	Chemical	D010126
+9284778	98	117	chlorofluorocarbons	Chemical	D017402
+9284778	131	155	Hydrochlorofluorocarbons	Chemical	-1
+9284778	157	162	HCFCs	Chemical	-1
+9284778	217	222	ozone	Chemical	D010126
+9284778	233	252	chlorofluorocarbons	Chemical	D017402
+9284778	254	258	CFCs	Chemical	D017402
+9284778	307	321	hepatotoxicity	Disease	D056486
+9284778	381	394	liver disease	Disease	D008107
+9284778	479	513	1,1-dichloro-2,2,2-trifluoroethane	Chemical	C067411
+9284778	515	523	HCFC 123	Chemical	C067411
+9284778	529	563	1-chloro-1,2,2,2-tetrafluoroethane	Chemical	C072959
+9284778	565	573	HCFC 124	Chemical	C072959
+9284778	685	723	1-bromo-1-chloro-2,2,2-trifluoroethane	Chemical	D006221
+9284778	725	734	halothane	Chemical	D006221
+9284778	753	768	trifluoroacetyl	Chemical	D014269
+9284778	825	839	hepatotoxicity	Disease	D056486
+9284778	843	852	halothane	Chemical	D006221
+9284778	879	896	HCFCs 123 and 124	Chemical	C067411|C072959	HCFCs 123|HCFCs 124
+9284778	919	932	liver disease	Disease	D008107
+9284778	1043	1058	trifluoroacetyl	Chemical	D014269
+9284778	1335	1343	necrosis	Disease	D009336
+9284778	1481	1489	necrosis	Disease	D009336
+9284778	1492	1507	Trifluoroacetyl	Chemical	D014269
+9284778	1633	1652	halothane hepatitis	Disease	C562477
+9284778	1760	1777	HCFCs 123 and 124	Chemical	C067411|C072959	HCFCs 123|HCFCs 124
+9284778	1800	1812	liver injury	Disease	D056486
+9284778	1894	1908	hepatotoxicity	Disease	D056486
+9284778	1964	1979	trifluoroacetyl	Chemical	D014269
+9284778	CID	C072959	D008107
+9284778	CID	C067411	D008107
+
+9522143|t|The effect of different anaesthetic agents in hearing loss following spinal anaesthesia.
+9522143|a|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.
+9522143	46	58	hearing loss	Disease	D034381
+9522143	102	114	hearing loss	Disease	D034381
+9522143	265	291	sensorineural hearing loss	Disease	D006319
+9522143	336	348	hearing loss	Disease	D034381
+9522143	408	420	hearing loss	Disease	D034381
+9522143	494	504	prilocaine	Chemical	D011318
+9522143	537	548	bupivacaine	Chemical	D002045
+9522143	570	580	prilocaine	Chemical	D011318
+9522143	609	621	hearing loss	Disease	D034381
+9522143	654	665	bupivacaine	Chemical	D002045
+9522143	704	716	hearing loss	Disease	D034381
+9522143	762	772	prilocaine	Chemical	D011318
+9522143	789	800	bupivacaine	Chemical	D002045
+9522143	848	860	hearing loss	Disease	D034381
+9522143	CID	D011318	D034381
+9522143	CID	D002045	D034381
+
+9522152|t|A transient neurological deficit following intrathecal injection of 1% hyperbaric bupivacaine for unilateral spinal anaesthesia.
+9522152|a|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.
+9522152	12	32	neurological deficit	Disease	D009461
+9522152	82	93	bupivacaine	Chemical	D002045
+9522152	161	181	neurological deficit	Disease	D009461
+9522152	259	270	bupivacaine	Chemical	D002045
+9522152	512	538	loss of pinprick sensation	Disease	D012678
+9522152	1135	1155	neurological deficit	Disease	D009461
+9522152	CID	D002045	D012678
+
+9672936|t|Pethidine-associated seizure in a healthy adolescent receiving pethidine for postoperative pain control.
+9672936|a|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.
+9672936	0	9	Pethidine	Chemical	D008614
+9672936	21	28	seizure	Disease	D012640
+9672936	63	72	pethidine	Chemical	D008614
+9672936	77	95	postoperative pain	Disease	D010149
+9672936	172	181	pethidine	Chemical	D008614
+9672936	246	264	postoperative pain	Disease	D010149
+9672936	339	346	seizure	Disease	D012640
+9672936	360	369	pethidine	Chemical	D008614
+9672936	374	386	norpethidine	Chemical	C002752
+9672936	522	530	toxicity	Disease	D064420
+9672936	592	601	pethidine	Chemical	D008614
+9672936	652	661	pethidine	Chemical	D008614
+9672936	666	678	norpethidine	Chemical	C002752
+9672936	699	708	pethidine	Chemical	D008614
+9672936	CID	D008614	D012640
+
+9721172|t|Drug-associated acute-onset vanishing bile duct and Stevens-Johnson syndromes in a child.
+9721172|a|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.
+9721172	28	47	vanishing bile duct	Disease	D001649
+9721172	52	77	Stevens-Johnson syndromes	Disease	D013262
+9721172	96	115	vanishing bile duct	Disease	D001649
+9721172	172	183	cholestasis	Disease	D002779
+9721172	313	337	Stevens-Johnson syndrome	Disease	D013262
+9721172	383	399	hypersensitivity	Disease	D004342
+9721172	449	458	infection	Disease	D007239
+9721172	612	640	vanishing bile duct syndrome	Disease	D001649
+9721172	655	679	Stevens-Johnson syndrome	Disease	D013262
+9721172	730	739	ibuprofen	Chemical	D007052
+9721172	766	786	ursodeoxycholic acid	Chemical	D014580
+9721172	788	798	prednisone	Chemical	D011241
+9721172	809	819	tacrolimus	Chemical	D016559
+9721172	825	844	cholestatic disease	Disease	D002779
+9721172	867	876	cirrhosis	Disease	D005355
+9721172	961	989	vanishing bile duct syndrome	Disease	D001649
+9721172	1083	1107	Stevens-Johnson syndrome	Disease	D013262
+9721172	1112	1140	vanishing bile duct syndrome	Disease	D001649
+9721172	CID	D007052	D013262
+9721172	CID	D007052	D002779
+
+9727773|t|High incidence of primary pulmonary hypertension associated with appetite suppressants in Belgium.
+9727773|a|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.
+9727773	18	48	primary pulmonary hypertension	Disease	D006976
+9727773	65	86	appetite suppressants	Chemical	D001067
+9727773	99	129	Primary pulmonary hypertension	Disease	D006976
+9727773	221	241	appetite suppressant	Chemical	D001067
+9727773	376	397	appetite suppressants	Chemical	D001067
+9727773	425	455	primary pulmonary hypertension	Disease	D006976
+9727773	546	567	appetite-suppressants	Chemical	D001067
+9727773	692	713	appetite suppressants	Chemical	D001067
+9727773	722	735	fenfluramines	Chemical	D005277
+9727773	866	887	appetite suppressants	Chemical	D001067
+9727773	920	950	primary pulmonary hypertension	Disease	D006976
+9727773	986	1007	appetite suppressants	Chemical	D001067
+9727773	1046	1067	appetite suppressants	Chemical	D001067
+9727773	1228	1249	appetite suppressants	Chemical	D001067
+9727773	1293	1323	primary pulmonary hypertension	Disease	D006976
+9727773	1335	1356	appetite suppressants	Chemical	D001067
+9727773	CID	D005277	D006976
+9727773	CID	D001067	D006976
+
+9754849|t|Choreoathetoid movements associated with rapid adjustment to methadone.
+9754849|a|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.
+9754849	0	24	Choreoathetoid movements	Disease	D002819
+9754849	61	70	methadone	Chemical	D008691
+9754849	72	98	Choreatiform hyperkinesias	Disease	D002819|D006948	Choreatiform|hyperkinesias
+9754849	126	148	movement abnormalities	Disease	D020820
+9754849	175	182	cocaine	Chemical	D003042
+9754849	238	262	choreoathetoid movements	Disease	D002819
+9754849	352	361	methadone	Chemical	D008691
+9754849	397	404	heroine	Chemical	D003932
+9754849	409	416	cocaine	Chemical	D003042
+9754849	CID	D008691	D002819
+9754849	CID	D003042	D006948
+9754849	CID	D003042	D002819
+
+10365197|t|Cocaine-induced mood disorder: prevalence rates and psychiatric symptoms in an outpatient cocaine-dependent sample.
+10365197|a|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.
+10365197	0	7	Cocaine	Chemical	D003042
+10365197	16	29	mood disorder	Disease	D019964
+10365197	52	63	psychiatric	Disease	D001523
+10365197	90	97	cocaine	Chemical	D003042
+10365197	232	246	mood disorders	Disease	D019964
+10365197	252	259	cocaine	Chemical	D003042
+10365197	287	294	cocaine	Chemical	D003042
+10365197	303	316	mood disorder	Disease	D019964
+10365197	318	322	CIMD	Disease	D019970
+10365197	331	345	mood disorders	Disease	D019964
+10365197	353	366	mood disorder	Disease	D019964
+10365197	396	407	psychiatric	Disease	D001523
+10365197	442	446	CIMD	Disease	D019970
+10365197	508	512	CIMD	Disease	D019970
+10365197	561	581	depressive disorders	Disease	D003866
+10365197	597	601	CIMD	Disease	D019970
+10365197	675	688	mood disorder	Disease	D019964
+10365197	759	763	CIMD	Disease	D019970
+10365197	CID	D003042	D019964
+
+10704919|t|Hemolysis of human erythrocytes induced by tamoxifen is related to disruption of membrane structure.
+10704919|a|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.
+10704919	0	9	Hemolysis	Disease	D006461
+10704919	43	52	tamoxifen	Chemical	D013629
+10704919	101	110	Tamoxifen	Chemical	D013629
+10704919	112	115	TAM	Chemical	D013629
+10704919	188	201	breast cancer	Disease	D001943
+10704919	263	279	hemolytic anemia	Disease	D000743
+10704919	316	319	TAM	Chemical	D013629
+10704919	404	407	TAM	Chemical	D013629
+10704919	416	432	hemolytic anemia	Disease	D000743
+10704919	506	509	TAM	Chemical	D013629
+10704919	518	527	hemolysis	Disease	D006461
+10704919	593	602	hemolysis	Disease	D006461
+10704919	657	660	TAM	Chemical	D013629
+10704919	675	684	hemolysis	Disease	D006461
+10704919	758	761	TAM	Chemical	D013629
+10704919	827	836	hemolytic	Disease	D006461
+10704919	847	850	TAM	Chemical	D013629
+10704919	889	905	alpha-tocopherol	Chemical	D024502
+10704919	907	914	alpha-T	Chemical	D024502
+10704919	920	944	alpha-tocopherol acetate	Chemical	D024502
+10704919	946	955	alpha-TAc	Chemical	D024502
+10704919	981	989	hydroxyl	Chemical	D017665
+10704919	1007	1010	TAM	Chemical	D013629
+10704919	1019	1028	hemolysis	Disease	D006461
+10704919	1115	1121	oxygen	Chemical	D010100
+10704919	1192	1195	TAM	Chemical	D013629
+10704919	1204	1213	hemolysis	Disease	D006461
+10704919	1249	1252	TAM	Chemical	D013629
+10704919	1312	1316	AAPH	Chemical	C046728
+10704919	1334	1337	TAM	Chemical	D013629
+10704919	1369	1378	Hemolysis	Disease	D006461
+10704919	1389	1392	TAM	Chemical	D013629
+10704919	1428	1429	K	Chemical	D011188
+10704919	1500	1509	hemolysis	Disease	D006461
+10704919	1574	1577	TAM	Chemical	D013629
+10704919	1699	1706	alpha-T	Chemical	D024502
+10704919	1710	1719	alpha-TAc	Chemical	D024502
+10704919	1760	1763	TAM	Chemical	D013629
+10704919	1843	1852	hemolysis	Disease	D006461
+10704919	1856	1867	tocopherols	Chemical	D024505
+10704919	1894	1897	TAM	Chemical	D013629
+10704919	2025	2028	TAM	Chemical	D013629
+10704919	2037	2046	hemolysis	Disease	D006461
+10704919	2339	2342	TAM	Chemical	D013629
+10704919	2357	2373	hemolytic anemia	Disease	D000743
+10704919	2514	2517	TAM	Chemical	D013629
+10704919	CID	D013629	D006461
+10704919	CID	D013629	D000743
+
+10706004|t|Changes of sodium and ATP affinities of the cardiac (Na,K)-ATPase during and after nitric oxide deficient hypertension.
+10706004|a|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.
+10706004	11	17	sodium	Chemical	D012964
+10706004	22	25	ATP	Chemical	D000255
+10706004	53	55	Na	Chemical	D012964
+10706004	56	57	K	Chemical	D011188
+10706004	83	95	nitric oxide	Chemical	D009569
+10706004	106	118	hypertension	Disease	D006973
+10706004	150	152	NO	Chemical	D009569
+10706004	224	226	NO	Chemical	D009569
+10706004	255	267	hypertension	Disease	D006973
+10706004	290	302	hypertension	Disease	D006973
+10706004	331	337	sodium	Chemical	D012964
+10706004	457	459	Na	Chemical	D012964
+10706004	498	500	Na	Chemical	D012964
+10706004	501	502	K	Chemical	D011188
+10706004	514	516	NO	Chemical	D009569
+10706004	527	539	hypertension	Disease	D006973
+10706004	559	561	NO	Chemical	D009569
+10706004	600	634	N(G)-nitro-L-arginine methyl ester	Chemical	D019331
+10706004	636	642	L-NAME	Chemical	D019331
+10706004	693	699	L-NAME	Chemical	D019331
+10706004	853	855	Na	Chemical	D012964
+10706004	856	857	K	Chemical	D011188
+10706004	885	888	ATP	Chemical	D000255
+10706004	940	942	NO	Chemical	D009569
+10706004	982	984	Na	Chemical	D012964
+10706004	1028	1029	K	Chemical	D011188
+10706004	1030	1032	Na	Chemical	D012964
+10706004	1106	1108	Na	Chemical	D012964
+10706004	1126	1128	NO	Chemical	D009569
+10706004	1165	1177	hypertension	Disease	D006973
+10706004	1196	1198	Na	Chemical	D012964
+10706004	1199	1200	K	Chemical	D011188
+10706004	1250	1253	ATP	Chemical	D000255
+10706004	1310	1313	ATP	Chemical	D000255
+10706004	1319	1320	K	Chemical	D011188
+10706004	1321	1323	Na	Chemical	D012964
+10706004	1335	1337	Na	Chemical	D012964
+10706004	1380	1382	NO	Chemical	D009569
+10706004	1413	1425	hypertension	Disease	D006973
+10706004	1441	1450	depressed	Disease	D003866
+10706004	1451	1453	Na	Chemical	D012964
+10706004	1517	1519	Na	Chemical	D012964
+10706004	1548	1550	Na	Chemical	D012964
+10706004	1551	1552	K	Chemical	D011188
+10706004	1631	1633	Na	Chemical	D012964
+10706004	1705	1707	Na	Chemical	D012964
+10706004	1708	1709	K	Chemical	D011188
+10706004	CID	D009569	D006973
+
+10721819|t|Effects of long-term pretreatment with isoproterenol on bromocriptine-induced tachycardia in conscious rats.
+10721819|a|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.
+10721819	39	52	isoproterenol	Chemical	D007545
+10721819	56	69	bromocriptine	Chemical	D001971
+10721819	78	89	tachycardia	Disease	D013610
+10721819	132	145	bromocriptine	Chemical	D001971
+10721819	154	165	tachycardia	Disease	D013610
+10721819	231	239	dopamine	Chemical	D004298
+10721819	289	302	isoproterenol	Chemical	D007545
+10721819	492	505	isoproterenol	Chemical	D007545
+10721819	520	533	bromocriptine	Chemical	D001971
+10721819	542	553	tachycardia	Disease	D013610
+10721819	573	586	Isoproterenol	Chemical	D007545
+10721819	619	638	cardiac hypertrophy	Disease	D006332
+10721819	726	739	bromocriptine	Chemical	D001971
+10721819	776	787	hypotension	Disease	D007022
+10721819	792	803	tachycardia	Disease	D013610
+10721819	805	818	Bromocriptine	Chemical	D001971
+10721819	827	838	hypotension	Disease	D007022
+10721819	857	870	isoproterenol	Chemical	D007545
+10721819	891	902	tachycardia	Disease	D013610
+10721819	931	942	bradycardia	Disease	D001919
+10721819	986	997	domperidone	Chemical	D004294
+10721819	1069	1082	isoproterenol	Chemical	D007545
+10721819	1142	1155	isoproterenol	Chemical	D007545
+10721819	1177	1190	isoproterenol	Chemical	D007545
+10721819	1335	1348	isoproterenol	Chemical	D007545
+10721819	1472	1485	isoproterenol	Chemical	D007545
+10721819	1531	1544	bromocriptine	Chemical	D001971
+10721819	1553	1564	tachycardia	Disease	D013610
+10721819	1568	1579	bradycardia	Disease	D001919
+10721819	1788	1799	tachycardia	Disease	D013610
+10721819	1803	1816	bromocriptine	Chemical	D001971
+10721819	1856	1867	bradycardia	Disease	D001919
+10721819	1898	1906	dopamine	Chemical	D004298
+10721819	CID	D007545	D001919
+10721819	CID	D004294	D001919
+10721819	CID	D001971	D007022
+10721819	CID	D007545	D006332
+10721819	CID	D001971	D013610
+
+10737864|t|A developmental analysis of clonidine's effects on cardiac rate and ultrasound production in infant rats.
+10737864|a|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.
+10737864	28	37	clonidine	Chemical	D003000
+10737864	269	278	clonidine	Chemical	D003000
+10737864	341	350	clonidine	Chemical	D003000
+10737864	539	548	clonidine	Chemical	D003000
+10737864	584	595	bradycardia	Disease	D001919
+10737864	618	627	clonidine	Chemical	D003000
+10737864	772	781	clonidine	Chemical	D003000
+10737864	1038	1047	clonidine	Chemical	D003000
+10737864	1056	1067	bradycardia	Disease	D001919
+10737864	1231	1240	clonidine	Chemical	D003000
+10737864	CID	D003000	D001919
+
+10743446|t|Differential effects of systemically administered ketamine and lidocaine on dynamic and static hyperalgesia induced by intradermal capsaicin in humans.
+10743446|a|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.
+10743446	50	58	ketamine	Chemical	D007649
+10743446	63	72	lidocaine	Chemical	D008012
+10743446	95	107	hyperalgesia	Disease	D006930
+10743446	131	140	capsaicin	Chemical	D002211
+10743446	210	218	ketamine	Chemical	D007649
+10743446	223	232	lidocaine	Chemical	D008012
+10743446	259	263	pain	Disease	D010146
+10743446	293	305	hyperalgesia	Disease	D006930
+10743446	317	326	capsaicin	Chemical	D002211
+10743446	443	452	Capsaicin	Chemical	D002211
+10743446	548	556	ketamine	Chemical	D007649
+10743446	638	647	lidocaine	Chemical	D008012
+10743446	723	732	capsaicin	Chemical	D002211
+10743446	775	779	pain	Disease	D010146
+10743446	781	785	pain	Disease	D010146
+10743446	876	888	hyperalgesia	Disease	D006930
+10743446	890	898	Ketamine	Chemical	D007649
+10743446	957	969	hyperalgesia	Disease	D006930
+10743446	1021	1025	pain	Disease	D010146
+10743446	1027	1036	Lidocaine	Chemical	D008012
+10743446	1073	1085	hyperalgesia	Disease	D006930
+10743446	1147	1151	pain	Disease	D010146
+10743446	1180	1184	pain	Disease	D010146
+10743446	1214	1222	ketamine	Chemical	D007649
+10743446	1227	1236	lidocaine	Chemical	D008012
+10743446	1259	1271	hyperalgesia	Disease	D006930
+10743446	1302	1314	hyperalgesia	Disease	D006930
+10743446	CID	D002211	D006930
+10743446	CID	D002211	D010146
+
+11007689|t|Cyclosporine and tacrolimus-associated thrombotic microangiopathy.
+11007689|a|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.
+11007689	0	12	Cyclosporine	Chemical	D016572
+11007689	17	27	tacrolimus	Chemical	D016559
+11007689	39	65	thrombotic microangiopathy	Disease	D057049
+11007689	86	112	thrombotic microangiopathy	Disease	D057049
+11007689	114	117	TMA	Disease	D057049
+11007689	146	158	cyclosporine	Chemical	D016572
+11007689	242	254	cyclosporine	Chemical	D016572
+11007689	584	594	tacrolimus	Chemical	D016559
+11007689	689	701	cyclosporine	Chemical	D016572
+11007689	729	739	tacrolimus	Chemical	D016559
+11007689	810	822	cyclosporine	Chemical	D016572
+11007689	831	834	TMA	Disease	D057049
+11007689	876	886	tacrolimus	Chemical	D016559
+11007689	913	923	tacrolimus	Chemical	D016559
+11007689	935	938	TMA	Disease	D057049
+11007689	1030	1033	TMA	Disease	D057049
+11007689	1070	1082	cyclosporine	Chemical	D016572
+11007689	1087	1097	tacrolimus	Chemical	D016559
+11007689	1186	1198	cyclosporine	Chemical	D016572
+11007689	1207	1210	TMA	Disease	D057049
+11007689	1247	1259	cyclosporine	Chemical	D016572
+11007689	1356	1366	tacrolimus	Chemical	D016559
+11007689	1439	1442	TMA	Disease	D057049
+11007689	1522	1534	cyclosporine	Chemical	D016572
+11007689	1538	1548	tacrolimus	Chemical	D016559
+11007689	1631	1634	TMA	Disease	D057049
+11007689	CID	D016572	D057049
+11007689	CID	D016559	D057049
+
+11256525|t|Repeated transient anuria following losartan administration in a patient with a solitary kidney.
+11256525|a|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.
+11256525	19	25	anuria	Disease	D001002
+11256525	36	44	losartan	Chemical	D019808
+11256525	133	145	hypertensive	Disease	D006973
+11256525	177	204	chronic renal insufficiency	Disease	D051436
+11256525	245	251	anuria	Disease	D001002
+11256525	258	266	losartan	Chemical	D019808
+11256525	309	330	myocardial infarction	Disease	D009203
+11256525	336	351	pulmonary edema	Disease	D011654
+11256525	401	421	systolic dysfunction	Disease	D006331
+11256525	422	430	losartan	Chemical	D019808
+11256525	488	496	losartan	Chemical	D019808
+11256525	518	524	anuria	Disease	D001002
+11256525	569	579	furosemide	Chemical	D005665
+11256525	584	589	amine	Chemical	D000588
+11256525	628	636	losartan	Chemical	D019808
+11256525	746	752	anuria	Disease	D001002
+11256525	842	853	hypotension	Disease	D007022
+11256525	910	931	renal artery stenosis	Disease	D012078
+11256525	950	971	renal artery stenosis	Disease	D012078
+11256525	986	999	heart failure	Disease	D006333
+11256525	1076	1087	angiotensin	Chemical	D000809
+11256525	1125	1139	angiotensin II	Chemical	D000804
+11256525	1161	1169	losartan	Chemical	D019808
+11256525	1284	1298	angiotensin II	Chemical	D000804
+11256525	1319	1327	losartan	Chemical	D019808
+11256525	1388	1408	renovascular disease	Disease	D014652
+11256525	CID	D019808	D001002
+
+11334364|t|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.
+11334364|a|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.
+11334364	58	66	necrotic	Disease	D009336
+11334364	86	99	acetaminophen	Chemical	D000082
+11334364	108	122	nephrotoxicity	Disease	D007674
+11334364	124	134	amiodarone	Chemical	D000638
+11334364	143	156	lung toxicity	Disease	D008171
+11334364	161	172	doxorubicin	Chemical	D004317
+11334364	181	195	cardiotoxicity	Disease	D066126
+11334364	207	248	IH636 grape seed proanthocyanidin extract	Chemical	C511402
+11334364	250	268	Grape seed extract	Chemical	C511402
+11334364	293	310	proanthocyanidins	Chemical	D044945
+11334364	477	518	IH636 grape seed proanthocyanidin extract	Chemical	C511402
+11334364	520	524	GSPE	Chemical	C511402
+11334364	537	550	acetaminophen	Chemical	D000082
+11334364	552	555	AAP	Chemical	D000082
+11334364	565	579	nephrotoxicity	Disease	D007674
+11334364	581	591	amiodarone	Chemical	D000638
+11334364	593	596	AMI	Chemical	D000638
+11334364	606	619	lung toxicity	Disease	D008171
+11334364	625	636	doxorubicin	Chemical	D004317
+11334364	638	641	DOX	Chemical	D004317
+11334364	651	665	cardiotoxicity	Disease	D066126
+11334364	746	750	GSPE	Chemical	C511402
+11334364	773	777	GSPE	Chemical	C511402
+11334364	852	856	GSPE	Chemical	C511402
+11334364	930	933	AAP	Chemical	D000082
+11334364	955	958	AMI	Chemical	D000638
+11334364	988	991	DOX	Chemical	D004317
+11334364	1303	1307	GSPE	Chemical	C511402
+11334364	1329	1332	AAP	Chemical	D000082
+11334364	1334	1337	AMI	Chemical	D000638
+11334364	1342	1345	DOX	Chemical	D004317
+11334364	1576	1589	tissue damage	Disease	D017695
+11334364	1675	1679	GSPE	Chemical	C511402
+11334364	1714	1718	GSPE	Chemical	C511402
+11334364	1955	1958	AAP	Chemical	D000082
+11334364	1960	1963	AMI	Chemical	D000638
+11334364	1968	1971	DOX	Chemical	D004317
+11334364	2011	2019	necrosis	Disease	D009336
+11334364	2083	2087	GSPE	Chemical	C511402
+11334364	2095	2098	AAP	Chemical	D000082
+11334364	2100	2103	AMI	Chemical	D000638
+11334364	2108	2111	DOX	Chemical	D004317
+11334364	2208	2212	GSPE	Chemical	C511402
+11334364	2500	2503	AMI	Chemical	D000638
+11334364	2599	2603	GSPE	Chemical	C511402
+11334364	CID	D000638	D009336
+11334364	CID	D004317	D009336
+11334364	CID	D000082	D009336
+11334364	CID	D000082	D007674
+11334364	CID	D000638	D008171
+11334364	CID	D004317	D066126
+
+11642480|t|Palpebral twitching in a depressed adolescent on citalopram.
+11642480|a|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.
+11642480	0	19	Palpebral twitching	Disease	D004409
+11642480	25	34	depressed	Disease	D003866
+11642480	49	59	citalopram	Chemical	D015283
+11642480	158	174	major depression	Disease	D003865
+11642480	225	235	citalopram	Chemical	D015283
+11642480	262	278	major depression	Disease	D003865
+11642480	293	312	palpebral twitching	Disease	D004409
+11642480	388	398	citalopram	Chemical	D015283
+11642480	CID	D015283	D004409
+
+12063090|t|Metamizol potentiates morphine antinociception but not constipation after chronic treatment.
+12063090|a|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.
+12063090	0	9	Metamizol	Chemical	D004177
+12063090	22	30	morphine	Chemical	D009020
+12063090	55	67	constipation	Disease	D003248
+12063090	137	149	constipating	Disease	D003248
+12063090	195	203	morphine	Chemical	D009020
+12063090	226	235	metamizol	Chemical	D004177
+12063090	400	404	pain	Disease	D010146
+12063090	450	458	charcoal	Chemical	D002606
+12063090	545	553	morphine	Chemical	D009020
+12063090	559	568	metamizol	Chemical	D004177
+12063090	819	827	morphine	Chemical	D009020
+12063090	1095	1103	naloxone	Chemical	D009270
+12063090	1230	1238	morphine	Chemical	D009020
+12063090	1393	1405	constipating	Disease	D003248
+12063090	1488	1496	morphine	Chemical	D009020
+12063090	1550	1559	metamizol	Chemical	D004177
+12063090	1579	1587	morphine	Chemical	D009020
+12063090	1596	1608	constipation	Disease	D003248
+12063090	1664	1672	morphine	Chemical	D009020
+12063090	1677	1686	metamizol	Chemical	D004177
+12063090	1786	1798	chronic pain	Disease	D059350
+12063090	CID	D009020	D003248
+
+12084448|t|Ifosfamide encephalopathy presenting with asterixis.
+12084448|a|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.
+12084448	0	10	Ifosfamide	Chemical	D007069
+12084448	11	25	encephalopathy	Disease	D001927
+12084448	42	51	asterixis	Disease	D020820
+12084448	99	109	ifosfamide	Chemical	D007069
+12084448	111	114	IFX	Chemical	D007069
+12084448	280	289	myoclonus	Disease	D009207
+12084448	347	357	ifosfamide	Chemical	D007069
+12084448	362	374	plasmacytoma	Disease	D010954
+12084448	562	593	structural lesions of the brain	Disease	D001927
+12084448	598	621	metabolic abnormalities	Disease	D008659
+12084448	757	771	encephalopathy	Disease	D001927
+12084448	795	805	ifosfamide	Chemical	D007069
+12084448	843	852	asterixis	Disease	D020820
+12084448	916	925	asterixis	Disease	D020820
+12084448	945	955	ifosfamide	Chemical	D007069
+12084448	1099	1108	myoclonus	Disease	D009207
+12084448	1139	1142	IFX	Chemical	D007069
+12084448	CID	D007069	D009207
+12084448	CID	D007069	D001927
+
+12684739|t|Sub-chronic low dose gamma-vinyl GABA (vigabatrin) inhibits cocaine-induced increases in nucleus accumbens dopamine.
+12684739|a|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.
+12684739	21	37	gamma-vinyl GABA	Chemical	D020888
+12684739	39	49	vigabatrin	Chemical	D020888
+12684739	60	67	cocaine	Chemical	D003042
+12684739	107	115	dopamine	Chemical	D004298
+12684739	128	144	gamma-Vinyl GABA	Chemical	D020888
+12684739	146	149	GVG	Chemical	D020888
+12684739	173	177	GABA	Chemical	D005680
+12684739	287	291	GABA	Chemical	D005680
+12684739	359	374	substance abuse	Disease	D019966
+12684739	401	421	visual field defects	Disease	D005128
+12684739	423	426	VFD	Disease	D005128
+12684739	522	525	GVG	Chemical	D020888
+12684739	529	536	cocaine	Chemical	D003042
+12684739	583	591	dopamine	Chemical	D004298
+12684739	593	595	DA	Chemical	D004298
+12684739	896	899	GVG	Chemical	D020888
+12684739	933	940	cocaine	Chemical	D003042
+12684739	1054	1057	GVG	Chemical	D020888
+12684739	1100	1107	cocaine	Chemical	D003042
+12684739	1129	1137	dopamine	Chemical	D004298
+12684739	CID	D020888	D005128
+
+12716030|t|Amount of bleeding and hematoma size in the collagenase-induced intracerebral hemorrhage rat model.
+12716030|a|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.
+12716030	10	18	bleeding	Disease	D006470
+12716030	23	31	hematoma	Disease	D006406
+12716030	64	88	intracerebral hemorrhage	Disease	D002543
+12716030	123	147	intracerebral hemorrhage	Disease	D002543
+12716030	149	152	ICH	Disease	D002543
+12716030	174	180	stroke	Disease	D020521
+12716030	298	301	ICH	Disease	D002543
+12716030	325	328	ICH	Disease	D002543
+12716030	347	350	ICH	Disease	D002543
+12716030	444	452	bleeding	Disease	D006470
+12716030	575	583	hematoma	Disease	D006406
+12716030	614	622	hematoma	Disease	D006406
+12716030	670	678	hematoma	Disease	D006406
+12716030	736	739	ICH	Disease	D002543
+12716030	758	761	ICH	Disease	D002543
+12716030	802	809	heparin	Chemical	D006493
+12716030	823	831	hematoma	Disease	D006406
+12716030	874	877	ICH	Disease	D002543
+12716030	894	902	bleeding	Disease	D006470
+12716030	977	980	ICH	Disease	D002543
+12716030	1022	1025	ICH	Disease	D002543
+12716030	1117	1120	ICH	Disease	D002543
+12716030	CID	D006493	D006406
+
+12757899|t|Estradiol reduces seizure-induced hippocampal injury in ovariectomized female but not in male rats.
+12757899|a|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.
+12757899	0	9	Estradiol	Chemical	D004958
+12757899	18	25	seizure	Disease	D012640
+12757899	34	52	hippocampal injury	Disease	D001930
+12757899	143	161	hippocampal injury	Disease	D001930
+12757899	173	184	kainic acid	Chemical	D007608
+12757899	193	211	status epilepticus	Disease	D013226
+12757899	213	215	SE	Disease	D013226
+12757899	245	261	17beta-estradiol	Chemical	D004958
+12757899	320	327	lithium	Chemical	D008094
+12757899	328	339	pilocarpine	Chemical	D010862
+12757899	348	350	SE	Disease	D013226
+12757899	393	409	17beta-estradiol	Chemical	D004958
+12757899	470	472	SE	Disease	D013226
+12757899	561	567	silver	Chemical	D012834
+12757899	635	637	SE	Disease	D013226
+12757899	639	655	17beta-Estradiol	Chemical	D004958
+12757899	748	764	17beta-Estradiol	Chemical	D004958
+12757899	861	870	estradiol	Chemical	D004958
+12757899	948	957	estradiol	Chemical	D004958
+12757899	961	968	seizure	Disease	D012640
+12757899	CID	D008094	D013226
+12757899	CID	D008094	D001930
+12757899	CID	D010862	D013226
+12757899	CID	D010862	D001930
+
+12905102|t|Delirium during clozapine treatment: incidence and associated risk factors.
+12905102|a|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.
+12905102	0	8	Delirium	Disease	D003693
+12905102	16	25	clozapine	Chemical	D003024
+12905102	119	127	delirium	Disease	D003693
+12905102	135	144	clozapine	Chemical	D003024
+12905102	255	266	psychiatric	Disease	D001523
+12905102	291	300	clozapine	Chemical	D003024
+12905102	378	386	delirium	Disease	D003693
+12905102	568	577	clozapine	Chemical	D003024
+12905102	688	696	Delirium	Disease	D003693
+12905102	1043	1052	clozapine	Chemical	D003024
+12905102	1109	1117	Delirium	Disease	D003693
+12905102	1139	1148	clozapine	Chemical	D003024
+12905102	1243	1251	Delirium	Disease	D003693
+12905102	CID	D003024	D003693
+
+14513889|t|Ketoconazole-induced neurologic sequelae.
+14513889|a|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.
+14513889	0	12	Ketoconazole	Chemical	D007654
+14513889	21	40	neurologic sequelae	Disease	D009422
+14513889	71	94	weakness of extremities	Disease	D018908
+14513889	96	110	legs paralysis	Disease	D010243
+14513889	112	122	dysarthria	Disease	D004401
+14513889	127	133	tremor	Disease	D014202
+14513889	164	176	ketoconazole	Chemical	D007654
+14513889	296	308	ketoconazole	Chemical	D007654
+14513889	540	562	adverse drug reactions	Disease	D064420
+14513889	CID	D007654	D004401
+14513889	CID	D007654	D018908
+14513889	CID	D007654	D014202
+14513889	CID	D007654	D010243
+
+15009014|t|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.
+15009014|a|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.
+15009014	154	175	vascular dysfunctions	Disease	D002561
+15009014	179	195	cluster headache	Disease	D003027
+15009014	197	213	Cluster headache	Disease	D003027
+15009014	286	320	intracranial vascular disturbances	Disease	D002561
+15009014	723	732	Capsaicin	Chemical	D002211
+15009014	785	827	increases in dural and cortical blood flow	Disease	D006940
+15009014	917	939	hexamethonium chloride	Chemical	D018738
+15009014	963	992	increases in dural blood flow	Disease	D006940
+15009014	1046	1054	atropine	Chemical	D001285
+15009014	1399	1412	acetylcholine	Chemical	D000109
+15009014	1500	1516	cluster headache	Disease	D003027
+15009014	CID	D002211	D002561
+15009014	CID	D002211	D006940
+
+15120741|t|Recurrent excitation in the dentate gyrus of a murine model of temporal lobe epilepsy.
+15120741|a|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.
+15120741	63	85	temporal lobe epilepsy	Disease	D004833
+15120741	113	124	pilocarpine	Chemical	D010862
+15120741	142	160	status epilepticus	Disease	D013226
+15120741	162	164	SE	Disease	D013226
+15120741	210	218	seizures	Disease	D012640
+15120741	479	490	pilocarpine	Chemical	D010862
+15120741	522	524	Mg	Chemical	D008274
+15120741	560	571	bicuculline	Chemical	D001640
+15120741	746	757	pilocarpine	Chemical	D010862
+15120741	795	797	SE	Disease	D013226
+15120741	802	804	SE	Disease	D013226
+15120741	1006	1015	glutamate	Chemical	D018698
+15120741	1044	1053	glutamate	Chemical	D018698
+15120741	1208	1210	SE	Disease	D013226
+15120741	1282	1284	SE	Disease	D013226
+15120741	1375	1382	seizure	Disease	D012640
+15120741	1451	1473	temporal lobe epilepsy	Disease	D004833
+15120741	CID	D010862	D013226
+15120741	CID	D010862	D012640
+
+15275829|t|The alpha3 and beta4 nicotinic acetylcholine receptor subunits are necessary for nicotine-induced seizures and hypolocomotion in mice.
+15275829|a|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.
+15275829	31	44	acetylcholine	Chemical	D000109
+15275829	81	89	nicotine	Chemical	D009538
+15275829	98	106	seizures	Disease	D012640
+15275829	111	125	hypolocomotion	Disease	D006948
+15275829	146	154	nicotine	Chemical	D009538
+15275829	168	181	acetylcholine	Chemical	D000109
+15275829	294	301	tremors	Disease	D014202
+15275829	306	314	seizures	Disease	D012640
+15275829	319	324	death	Disease	D003643
+15275829	563	571	nicotine	Chemical	D009538
+15275829	580	588	seizures	Disease	D012640
+15275829	593	607	hypolocomotion	Disease	D006948
+15275829	734	742	nicotine	Chemical	D009538
+15275829	860	868	nicotine	Chemical	D009538
+15275829	877	885	seizures	Disease	D012640
+15275829	1218	1226	nicotine	Chemical	D009538
+15275829	1235	1243	seizures	Disease	D012640
+15275829	1459	1467	nicotine	Chemical	D009538
+15275829	1476	1484	seizures	Disease	D012640
+15275829	1489	1503	hypolocomotion	Disease	D006948
+15275829	CID	D009538	D012640
+
+15602202|t|Recurrent acute interstitial nephritis induced by azithromycin.
+15602202|a|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.
+15602202	16	38	interstitial nephritis	Disease	D009395
+15602202	50	62	azithromycin	Chemical	D017963
+15602202	111	123	azithromycin	Chemical	D017963
+15602202	139	161	interstitial nephritis	Disease	D009395
+15602202	366	388	interstitial nephritis	Disease	D009395
+15602202	458	470	renal injury	Disease	D007674
+15602202	CID	D017963	D009395
+
+16181582|t|Valproate-induced encephalopathy.
+16181582|a|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.
+16181582	0	9	Valproate	Chemical	D014635
+16181582	18	32	encephalopathy	Disease	D001927
+16181582	34	43	Valproate	Chemical	D014635
+16181582	52	66	encephalopathy	Disease	D001927
+16181582	124	133	epileptic	Disease	D004827
+16181582	280	294	hyperammonemia	Disease	D022124
+16181582	392	401	valproate	Chemical	D014635
+16181582	410	424	encephalopathy	Disease	D001927
+16181582	CID	D014635	D001927
+
+16298782|t|Nitro-L-arginine methyl ester: a potential protector against gentamicin ototoxicity.
+16298782|a|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.
+16298782	0	29	Nitro-L-arginine methyl ester	Chemical	D019331
+16298782	61	71	gentamicin	Chemical	D005839
+16298782	72	83	ototoxicity	Disease	D006311
+16298782	89	101	nitric oxide	Chemical	D009569
+16298782	103	105	NO	Chemical	D009569
+16298782	117	146	nitro-L-arginine methyl ester	Chemical	D019331
+16298782	148	154	L-NAME	Chemical	D019331
+16298782	192	219	high-frequency hearing loss	Disease	D006316
+16298782	230	240	gentamicin	Chemical	D005839
+16298782	289	303	Aminoglycoside	Chemical	D000617
+16298782	386	397	ototoxicity	Disease	D006311
+16298782	440	448	ototoxic	Disease	D006311
+16298782	486	488	NO	Chemical	D009569
+16298782	519	521	NO	Chemical	D009569
+16298782	555	569	aminoglycoside	Chemical	D000617
+16298782	578	604	sensorineural hearing loss	Disease	D006319
+16298782	681	691	gentamicin	Chemical	D005839
+16298782	741	747	L-NAME	Chemical	D019331
+16298782	846	858	hearing loss	Disease	D034381
+16298782	925	931	L-NAME	Chemical	D019331
+16298782	940	950	gentamicin	Chemical	D005839
+16298782	959	971	hearing loss	Disease	D034381
+16298782	CID	D005839	D034381
+
+16428221|t|Cerebral vasculitis following oral methylphenidate intake in an adult: a case report.
+16428221|a|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.
+16428221	0	19	Cerebral vasculitis	Disease	D020293
+16428221	35	50	methylphenidate	Chemical	D008774
+16428221	86	101	Methylphenidate	Chemical	D008774
+16428221	146	157	amphetamine	Chemical	D000661
+16428221	159	178	Cerebral vasculitis	Disease	D020293
+16428221	195	212	amphetamine abuse	Disease	D019969
+16428221	251	267	ischaemic stroke	Disease	D002544
+16428221	292	307	methylphenidate	Chemical	D008774
+16428221	392	407	methylphenidate	Chemical	D008774
+16428221	415	428	hyperactivity	Disease	D006948
+16428221	456	473	ischaemic strokes	Disease	D002544
+16428221	500	519	cerebral vasculitis	Disease	D020293
+16428221	558	575	ischaemic strokes	Disease	D002544
+16428221	668	683	methylphenidate	Chemical	D008774
+16428221	693	703	vasculitis	Disease	D014657
+16428221	781	796	methylphenidate	Chemical	D008774
+16428221	916	931	methylphenidate	Chemical	D008774
+16428221	CID	D008774	D020293
+
+16858720|t|Cerebral haemorrhage induced by warfarin - the influence of drug-drug interactions.
+16858720|a|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.
+16858720	0	20	Cerebral haemorrhage	Disease	D002543
+16858720	32	40	warfarin	Chemical	D014859
+16858720	151	159	warfarin	Chemical	D014859
+16858720	168	189	cerebral haemorrhages	Disease	D002543
+16858720	197	205	warfarin	Chemical	D014859
+16858720	210	218	warfarin	Chemical	D014859
+16858720	335	355	cerebral haemorrhage	Disease	D002543
+16858720	485	493	warfarin	Chemical	D014859
+16858720	498	506	warfarin	Chemical	D014859
+16858720	547	567	cerebral haemorrhage	Disease	D002543
+16858720	685	705	cerebral haemorrhage	Disease	D002543
+16858720	744	752	warfarin	Chemical	D014859
+16858720	903	911	warfarin	Chemical	D014859
+16858720	935	943	warfarin	Chemical	D014859
+16858720	991	1002	haemorrhage	Disease	D006470
+16858720	1022	1030	warfarin	Chemical	D014859
+16858720	1068	1076	bleeding	Disease	D006470
+16858720	1143	1151	Warfarin	Chemical	D014859
+16858720	1160	1181	cerebral haemorrhages	Disease	D002543
+16858720	1280	1288	warfarin	Chemical	D014859
+16858720	1335	1343	warfarin	Chemical	D014859
+16858720	1352	1373	cerebral haemorrhages	Disease	D002543
+16858720	1480	1488	warfarin	Chemical	D014859
+16858720	CID	D014859	D002543
+
+17466854|t|Side effects of postoperative administration of methylprednisolone and gentamicin into the posterior sub-Tenon's space.
+17466854|a|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.
+17466854	48	66	methylprednisolone	Chemical	D008775
+17466854	71	81	gentamicin	Chemical	D005839
+17466854	218	236	methylprednisolone	Chemical	D008775
+17466854	241	251	gentamicin	Chemical	D005839
+17466854	311	319	cataract	Disease	D002386
+17466854	561	571	lignocaine	Chemical	D008012
+17466854	639	657	methylprednisolone	Chemical	D008775
+17466854	678	688	gentamicin	Chemical	D005839
+17466854	887	903	nausea, vomiting	Disease	D020250
+17466854	909	917	headache	Disease	D006261
+17466854	1041	1070	postoperative emetic symptoms	Disease	D020250
+17466854	1072	1080	headache	Disease	D006261
+17466854	1167	1185	methylprednisolone	Chemical	D008775
+17466854	1190	1200	gentamicin	Chemical	D005839
+17466854	1294	1310	nausea, vomiting	Disease	D020250
+17466854	1316	1324	headache	Disease	D006261
+17466854	CID	D005839	D006261
+17466854	CID	D008775	D020250
+17466854	CID	D008775	D006261
+17466854	CID	D005839	D020250
+
+17562951|t|Cardiac Angiography in Renally Impaired Patients (CARE) study: a randomized double-blind trial of contrast-induced nephropathy in patients with chronic kidney disease.
+17562951|a|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.
+17562951	115	126	nephropathy	Disease	D007674
+17562951	144	166	chronic kidney disease	Disease	D051436
+17562951	256	271	contrast medium	Chemical	D003287
+17562951	272	281	iopamidol	Chemical	D007479
+17562951	314	329	contrast medium	Chemical	D003287
+17562951	330	339	iodixanol	Chemical	C044834
+17562951	459	468	iopamidol	Chemical	D007479
+17562951	473	482	iodixanol	Chemical	C044834
+17562951	500	522	chronic kidney disease	Disease	D051436
+17562951	659	669	creatinine	Chemical	D003404
+17562951	1104	1121	diabetes mellitus	Disease	D003920
+17562951	1130	1146	N-acetylcysteine	Chemical	D000111
+17562951	1315	1324	iopamidol	Chemical	D007479
+17562951	1361	1370	iodixanol	Chemical	C044834
+17562951	1484	1492	diabetes	Disease	D003920
+17562951	1559	1568	iopamidol	Chemical	D007479
+17562951	1604	1613	iodixanol	Chemical	C044834
+17562951	1755	1764	iopamidol	Chemical	D007479
+17562951	1854	1862	diabetes	Disease	D003920
+17562951	1967	1978	nephropathy	Disease	D007674
+17562951	2085	2094	iopamidol	Chemical	D007479
+17562951	2098	2107	iodixanol	Chemical	C044834
+17562951	2147	2164	diabetes mellitus	Disease	D003920
+17562951	CID	C044834	D007674
+17562951	CID	D003287	D007674
+17562951	CID	D007479	D007674
+
+17600377|t|A novel compound, maltolyl p-coumarate, attenuates cognitive deficits and shows neuroprotective effects in vitro and in vivo dementia models.
+17600377|a|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.
+17600377	18	38	maltolyl p-coumarate	Chemical	C524754
+17600377	51	69	cognitive deficits	Disease	D003072
+17600377	125	133	dementia	Disease	D003704
+17600377	260	280	maltolyl p-coumarate	Chemical	C524754
+17600377	306	312	maltol	Chemical	C008316
+17600377	317	332	p-coumaric acid	Chemical	C032171
+17600377	380	400	maltolyl p-coumarate	Chemical	C524754
+17600377	415	432	cognitive decline	Disease	D003072
+17600377	436	447	scopolamine	Chemical	D012601
+17600377	469	495	amyloid beta peptide(1-42)	Chemical	C544092
+17600377	510	530	Maltolyl p-coumarate	Chemical	C524754
+17600377	554	572	cognitive deficits	Disease	D003072
+17600377	691	717	amyloid beta peptide(1-42)	Chemical	C544092
+17600377	780	800	maltolyl p-coumarate	Chemical	C524754
+17600377	858	878	maltolyl p-coumarate	Chemical	C524754
+17600377	898	924	amyloid beta peptide(1-42)	Chemical	C544092
+17600377	926	935	glutamate	Chemical	D018698
+17600377	939	943	H2O2	Chemical	D006861
+17600377	959	979	maltolyl p-coumarate	Chemical	C524754
+17600377	1186	1206	maltolyl p-coumarate	Chemical	C524754
+17600377	1252	1271	Alzheimer's disease	Disease	D000544
+17600377	1309	1323	neuronal death	Disease	D009410
+17600377	1340	1369	decline of cognitive function	Disease	D003072
+17600377	CID	D012601	D003072
+
+17639754|t|Interaction between warfarin and levofloxacin: case series.
+17639754|a|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.
+17639754	20	28	warfarin	Chemical	D014859
+17639754	33	45	levofloxacin	Chemical	D064704
+17639754	60	68	Warfarin	Chemical	D014859
+17639754	159	171	Levofloxacin	Chemical	D064704
+17639754	175	190	fluoroquinolone	Chemical	D024841
+17639754	438	446	warfarin	Chemical	D014859
+17639754	451	463	levofloxacin	Chemical	D064704
+17639754	506	518	levofloxacin	Chemical	D064704
+17639754	578	586	warfarin	Chemical	D014859
+17639754	617	625	bleeding	Disease	D006470
+17639754	696	704	warfarin	Chemical	D014859
+17639754	709	721	levofloxacin	Chemical	D064704
+17639754	813	825	levofloxacin	Chemical	D064704
+17639754	845	853	warfarin	Chemical	D014859
+17639754	CID	D014859	D006470
+17639754	CID	D064704	D006470
+
+17854040|t|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.
+17854040|a|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.
+17854040	26	36	lamivudine	Chemical	D019259
+17854040	59	61	na	Chemical	D012964
+17854040	66	98	hepatitis B virus (HBV) infected	Disease	D006509
+17854040	125	141	HIV co-infection	Disease	D015658
+17854040	186	209	HBV and HIV co-infected	Disease	D006509|D015658	HBV infected|HIV infected
+17854040	279	289	lamivudine	Chemical	D019259
+17854040	300	311	hepatitis B	Disease	D006509
+17854040	344	354	lamivudine	Chemical	D019259
+17854040	355	357	na	Chemical	D012964
+17854040	392	439	human immunodeficiency virus (HIV) co-infection	Disease	D015658
+17854040	479	489	lamivudine	Chemical	D019259
+17854040	490	492	na	Chemical	D012964
+17854040	497	509	HBV infected	Disease	D006509
+17854040	535	551	HIV co-infection	Disease	D015658
+17854040	577	594	HBV mono-infected	Disease	D006509
+17854040	611	630	HBV-HIV co-infected	Disease	D006509|D015658	HBV infected|HIV infected
+17854040	702	707	HBsAg	Chemical	D006514
+17854040	735	740	HBsAg	Chemical	D006514
+17854040	762	767	HBsAg	Chemical	D006514
+17854040	1031	1039	tyrosine	Chemical	D014443
+17854040	1040	1050	methionine	Chemical	D008715
+17854040	1051	1060	aspartate	Chemical	D001224
+17854040	1061	1070	aspartate	Chemical	D001224
+17854040	1261	1271	lamivudine	Chemical	D019259
+17854040	1337	1348	hepatitis B	Disease	D006509
+17854040	1371	1390	HBV-HIV co-infected	Disease	D006509|D015658	HBV infected|HIV infected
+17854040	1472	1482	lamivudine	Chemical	D019259
+17854040	1512	1514	na	Chemical	D012964
+17854040	1519	1538	HBV-HIV co-infected	Disease	D006509|D015658	HBV infected|HIV infected
+17854040	1838	1848	lamivudine	Chemical	D019259
+17854040	2031	2050	HBV-HIV co-infected	Disease	D006509|D015658	HBV infected|HIV infected
+17854040	CID	D006514	D006509
+
+18221780|t|Sex differences in NMDA antagonist enhancement of morphine antihyperalgesia in a capsaicin model of persistent pain: comparisons to two models of acute pain.
+18221780|a|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.
+18221780	19	23	NMDA	Chemical	D016202
+18221780	50	58	morphine	Chemical	D009020
+18221780	81	90	capsaicin	Chemical	D002211
+18221780	111	115	pain	Disease	D010146
+18221780	146	156	acute pain	Disease	D059787
+18221780	161	171	acute pain	Disease	D059787
+18221780	180	200	N-methyl-D-aspartate	Chemical	D016202
+18221780	202	206	NMDA	Chemical	D016202
+18221780	259	267	morphine	Chemical	D009020
+18221780	390	394	pain	Disease	D010146
+18221780	435	445	acute pain	Disease	D059787
+18221780	595	607	hyperalgesia	Disease	D006930
+18221780	641	650	capsaicin	Chemical	D002211
+18221780	854	864	acute pain	Disease	D059787
+18221780	959	963	NMDA	Chemical	D016202
+18221780	975	991	dextromethorphan	Chemical	D003915
+18221780	1057	1065	morphine	Chemical	D009020
+18221780	1209	1217	morphine	Chemical	D009020
+18221780	1237	1253	dextromethorphan	Chemical	D003915
+18221780	1296	1306	acute pain	Disease	D059787
+18221780	1441	1445	NMDA	Chemical	D016202
+18221780	1462	1470	morphine	Chemical	D009020
+18221780	1487	1491	pain	Disease	D010146
+18221780	1547	1557	acute pain	Disease	D059787
+18221780	CID	D002211	D006930
+
+18261172|t|Development of proteinuria after switch to sirolimus-based immunosuppression in long-term cardiac transplant patients.
+18261172|a|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.
+18261172	15	26	proteinuria	Disease	D011507
+18261172	43	52	sirolimus	Chemical	D020123
+18261172	161	178	renal dysfunction	Disease	D007674
+18261172	252	260	sirolmus	Chemical	D020123
+18261172	262	265	Srl	Chemical	D020123
+18261172	273	284	nephrotoxic	Disease	D007674
+18261172	303	314	proteinuria	Disease	D011507
+18261172	331	334	Srl	Chemical	D020123
+18261172	431	442	proteinuria	Disease	D011507
+18261172	459	462	Srl	Chemical	D020123
+18261172	547	559	cyclosporine	Chemical	D016572
+18261172	563	566	Srl	Chemical	D020123
+18261172	605	626	mycophenolate mofetil	Chemical	C063008
+18261172	631	639	steroids	Chemical	D013256
+18261172	842	853	proteinuria	Disease	D011507
+18261172	916	929	ACE inhibitor	Chemical	D000806
+18261172	934	963	angiotensin-releasing blocker	Chemical	D057911
+18261172	965	968	ARB	Chemical	D057911
+18261172	986	997	proteinuria	Disease	D011507
+18261172	1028	1039	proteinuria	Disease	D011507
+18261172	1145	1156	proteinuria	Disease	D011507
+18261172	1254	1265	proteinuria	Disease	D011507
+18261172	1325	1328	Srl	Chemical	D020123
+18261172	1400	1403	Srl	Chemical	D020123
+18261172	1424	1428	ACEi	Chemical	D000806
+18261172	1429	1432	ARB	Chemical	D057911
+18261172	1468	1479	proteinuria	Disease	D011507
+18261172	1494	1511	renal dysfunction	Disease	D007674
+18261172	CID	D020123	D011507
+
+18329269|t|Synthesis of N-pyrimidinyl-2-phenoxyacetamides as adenosine A2A receptor antagonists.
+18329269|a|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.
+18329269	13	46	N-pyrimidinyl-2-phenoxyacetamides	Chemical	D010642
+18329269	50	59	adenosine	Chemical	D000241
+18329269	98	130	N-pyrimidinyl-2-phenoxyacetamide	Chemical	D010642
+18329269	131	140	adenosine	Chemical	D000241
+18329269	320	331	haloperidol	Chemical	D006220
+18329269	340	349	catalepsy	Disease	D002375
+18329269	360	379	Parkinson's disease	Disease	D010300
+18329269	CID	D006220	D002375
+
+18410508|t|Methamphetamine-induced neurotoxicity and microglial activation are not mediated by fractalkine receptor signaling.
+18410508|a|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.
+18410508	0	15	Methamphetamine	Chemical	D008694
+18410508	24	37	neurotoxicity	Disease	D020258
+18410508	116	131	Methamphetamine	Chemical	D008694
+18410508	133	137	METH	Chemical	D008694
+18410508	147	155	dopamine	Chemical	D004298
+18410508	157	159	DA	Chemical	D004298
+18410508	466	470	MPTP	Chemical	D015632
+18410508	479	496	neurodegeneration	Disease	D009422
+18410508	500	502	DA	Chemical	D004298
+18410508	524	534	CNS damage	Disease	D009422
+18410508	545	549	METH	Chemical	D008694
+18410508	554	558	MPTP	Chemical	D015632
+18410508	587	589	DA	Chemical	D004298
+18410508	625	638	neurotoxicity	Disease	D020258
+18410508	688	692	METH	Chemical	D008694
+18410508	701	714	neurotoxicity	Disease	D020258
+18410508	883	887	METH	Chemical	D008694
+18410508	914	927	neurotoxicity	Disease	D020258
+18410508	929	933	METH	Chemical	D008694
+18410508	943	945	DA	Chemical	D004298
+18410508	1124	1128	METH	Chemical	D008694
+18410508	1302	1306	METH	Chemical	D008694
+18410508	1498	1502	METH	Chemical	D008694
+18410508	1575	1579	METH	Chemical	D008694
+18410508	1580	1593	neurotoxicity	Disease	D020258
+18410508	1688	1692	METH	Chemical	D008694
+18410508	CID	D008694	D009422
+18410508	CID	D015632	D009422
+
+18503483|t|Recovery of tacrolimus-associated brachial neuritis after conversion to everolimus in a pediatric renal transplant recipient--case report and review of the literature.
+18503483|a|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.
+18503483	12	22	tacrolimus	Chemical	D016559
+18503483	34	51	brachial neuritis	Disease	D020968
+18503483	72	82	everolimus	Chemical	C107135
+18503483	168	171	TAC	Chemical	D016559
+18503483	273	286	Neurotoxicity	Disease	D020258
+18503483	349	363	encephalopathy	Disease	D001927
+18503483	365	374	headaches	Disease	D006261
+18503483	376	384	seizures	Disease	D012640
+18503483	389	410	neurological deficits	Disease	D009461
+18503483	617	625	myelitis	Disease	D009187
+18503483	636	653	brachial plexitis	Disease	D020968
+18503483	699	702	TAC	Chemical	D016559
+18503483	760	778	methylprednisolone	Chemical	D008775
+18503483	855	858	TAC	Chemical	D016559
+18503483	916	926	everolimus	Chemical	C107135
+18503483	CID	D016559	D020968
+
+18560792|t|Valvular heart disease in patients with Parkinson's disease treated with pergolide. Course following treatment modifications.
+18560792|a|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.
+18560792	0	22	Valvular heart disease	Disease	D006349
+18560792	40	59	Parkinson's disease	Disease	D010300
+18560792	73	82	pergolide	Chemical	D010479
+18560792	126	154	Valvular heart abnormalities	Disease	D006349
+18560792	191	210	Parkinson's disease	Disease	D010300
+18560792	212	214	PD	Disease	D010300
+18560792	229	238	pergolide	Chemical	D010479
+18560792	455	481	valvular heart abnormality	Disease	D006349
+18560792	573	575	PD	Disease	D010300
+18560792	617	626	pergolide	Chemical	D010479
+18560792	724	726	PD	Disease	D010300
+18560792	838	847	pergolide	Chemical	D010479
+18560792	915	917	PD	Disease	D010300
+18560792	997	1017	aortic regurgitation	Disease	D001022
+18560792	1049	1069	mitral regurgitation	Disease	D008944
+18560792	1119	1121	PD	Disease	D010300
+18560792	1298	1307	pergolide	Chemical	D010479
+18560792	1365	1374	pergolide	Chemical	D010479
+18560792	1417	1439	valvular regurgitation	Disease	D006349
+18560792	1467	1476	pergolide	Chemical	D010479
+18560792	1534	1547	heart failure	Disease	D006333
+18560792	1549	1558	Pergolide	Chemical	D010479
+18560792	1596	1618	valvular heart disease	Disease	D006349
+18560792	1741	1754	heart failure	Disease	D006333
+18560792	1857	1876	valve regurgitation	Disease	D006349
+18560792	1880	1882	PD	Disease	D010300
+18560792	1905	1914	pergolide	Chemical	D010479
+18560792	2012	2020	dopamine	Chemical	D004298
+18560792	CID	D010479	D001022
+18560792	CID	D010479	D008944
+
+18726058|t|Adverse effects of topical papaverine on auditory nerve function.
+18726058|a|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.
+18726058	27	37	papaverine	Chemical	D010208
+18726058	78	102	Papaverine hydrochloride	Chemical	D010208
+18726058	149	158	vasospasm	Disease	D020301
+18726058	210	235	cranial nerve dysfunction	Disease	D003389
+18726058	283	293	papaverine	Chemical	D010208
+18726058	567	577	papaverine	Chemical	D010208
+18726058	582	591	vasospasm	Disease	D020301
+18726058	601	611	papaverine	Chemical	D010208
+18726058	662	671	vasospasm	Disease	D020301
+18726058	713	723	papaverine	Chemical	D010208
+18726058	1017	1027	papaverine	Chemical	D010208
+18726058	1115	1125	papaverine	Chemical	D010208
+18726058	1267	1277	papaverine	Chemical	D010208
+18726058	1426	1452	sensorineural hearing loss	Disease	D006319
+18726058	1505	1515	papaverine	Chemical	D010208
+18726058	1565	1575	papaverine	Chemical	D010208
+18726058	1597	1606	vasospasm	Disease	D020301
+18726058	1838	1881	adverse effect on the proximal eighth nerve	Disease	D000160
+18726058	1918	1940	cranial nerve deficits	Disease	D003389
+18726058	1946	1956	papaverine	Chemical	D010208
+18726058	CID	D010208	D000160
+18726058	CID	D010208	D006319
+
+18754075|t|Massive proteinuria and acute renal failure after oral bisphosphonate (alendronate) administration in a patient with focal segmental glomerulosclerosis.
+18754075|a|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.
+18754075	8	19	proteinuria	Disease	D011507
+18754075	24	43	acute renal failure	Disease	D058186
+18754075	55	69	bisphosphonate	Chemical	D004164
+18754075	71	82	alendronate	Chemical	D019386
+18754075	117	151	focal segmental glomerulosclerosis	Disease	D005923
+18754075	185	203	nephrotic syndrome	Disease	D009404
+18754075	211	245	focal segmental glomerulosclerosis	Disease	D005923
+18754075	279	286	steroid	Chemical	D013256
+18754075	389	403	bisphosphonate	Chemical	D004164
+18754075	405	423	alendronate sodium	Chemical	D019386
+18754075	513	532	acute renal failure	Disease	D058186
+18754075	563	574	alendronate	Chemical	D019386
+18754075	684	694	creatinine	Chemical	D003404
+18754075	860	875	bisphosphonates	Chemical	D004164
+18754075	890	901	proteinuria	Disease	D011507
+18754075	906	925	acute renal failure	Disease	D058186
+18754075	CID	D019386	D058186
+18754075	CID	D019386	D011507
+
+18768591|t|Serum- and glucocorticoid-inducible kinase 1 in doxorubicin-induced nephrotic syndrome.
+18768591|a|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.
+18768591	48	59	doxorubicin	Chemical	D004317
+18768591	68	86	nephrotic syndrome	Disease	D009404
+18768591	88	99	Doxorubicin	Chemical	D004317
+18768591	108	119	nephropathy	Disease	D007674
+18768591	140	146	sodium	Chemical	D012964
+18768591	172	188	volume retention	Disease	D016055
+18768591	199	207	fibrosis	Disease	D005355
+18768591	213	224	aldosterone	Chemical	D000450
+18768591	361	369	fibrosis	Disease	D005355
+18768591	484	500	volume retention	Disease	D016055
+18768591	505	513	fibrosis	Disease	D005355
+18768591	521	539	nephrotic syndrome	Disease	D009404
+18768591	554	565	doxorubicin	Chemical	D004317
+18768591	706	717	Doxorubicin	Chemical	D004317
+18768591	746	757	proteinuria	Disease	D011507
+18768591	852	870	nephrotic syndrome	Disease	D009404
+18768591	876	883	ascites	Disease	D001201
+18768591	885	894	lipidemia	Disease	D006949
+18768591	900	915	hypoalbuminemia	Disease	D034141
+18768591	942	953	aldosterone	Chemical	D000450
+18768591	974	983	nephrotic	Disease	D009404
+18768591	1088	1094	sodium	Chemical	D012964
+18768591	1282	1293	weight gain	Disease	D015430
+18768591	1392	1410	nephrotic syndrome	Disease	D009404
+18768591	1418	1422	urea	Chemical	D014508
+18768591	1521	1527	uremia	Disease	D014511
+18768591	1674	1690	volume retention	Disease	D016055
+18768591	1729	1737	fibrosis	Disease	D005355
+18768591	1758	1776	nephrotic syndrome	Disease	D009404
+18768591	CID	D004317	D001201
+18768591	CID	D004317	D006949
+18768591	CID	D004317	D011507
+18768591	CID	D004317	D009404
+18768591	CID	D004317	D034141
+
+19299179|t|Severe and long lasting cholestasis after high-dose co-trimoxazole treatment for Pneumocystis pneumonia in HIV-infected patients--a report of two cases.
+19299179|a|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.
+19299179	24	35	cholestasis	Disease	D002779
+19299179	52	66	co-trimoxazole	Chemical	D015662
+19299179	81	103	Pneumocystis pneumonia	Disease	D011020
+19299179	107	119	HIV-infected	Disease	D015658
+19299179	153	175	Pneumocystis pneumonia	Disease	D011020
+19299179	177	180	PCP	Disease	D011020
+19299179	192	215	opportunistic infection	Disease	D009894
+19299179	219	231	HIV-infected	Disease	D015658
+19299179	285	299	co-trimoxazole	Chemical	D015662
+19299179	413	425	HIV-infected	Disease	D015658
+19299179	456	480	intrahepatic cholestasis	Disease	D002780
+19299179	519	532	liver abscess	Disease	D008100
+19299179	571	585	co-trimoxazole	Chemical	D015662
+19299179	600	603	PCP	Disease	D011020
+19299179	717	731	co-trimoxazole	Chemical	D015662
+19299179	CID	D015662	D002780
+
+19356053|t|Clinically significant proteinuria following the administration of sirolimus to renal transplant recipients.
+19356053|a|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.
+19356053	23	34	proteinuria	Disease	D011507
+19356053	67	76	sirolimus	Chemical	D020123
+19356053	121	130	Sirolimus	Chemical	D020123
+19356053	214	228	nephrotoxicity	Disease	D007674
+19356053	348	359	proteinuria	Disease	D011507
+19356053	383	392	sirolimus	Chemical	D020123
+19356053	457	468	proteinuria	Disease	D011507
+19356053	485	494	sirolimus	Chemical	D020123
+19356053	576	585	sirolimus	Chemical	D020123
+19356053	598	609	proteinuria	Disease	D011507
+19356053	621	630	sirolimus	Chemical	D020123
+19356053	666	677	proteinuria	Disease	D011507
+19356053	845	854	sirolimus	Chemical	D020123
+19356053	943	954	proteinuria	Disease	D011507
+19356053	1046	1056	creatinine	Chemical	D003404
+19356053	1089	1100	proteinuria	Disease	D011507
+19356053	1175	1184	sirolimus	Chemical	D020123
+19356053	1247	1258	proteinuria	Disease	D011507
+19356053	1354	1365	proteinuria	Disease	D011507
+19356053	1530	1539	sirolimus	Chemical	D020123
+19356053	1563	1572	nephrotic	Disease	D009404
+19356053	1579	1590	proteinuria	Disease	D011507
+19356053	1592	1603	Proteinuria	Disease	D011507
+19356053	1634	1643	sirolimus	Chemical	D020123
+19356053	1748	1757	sirolimus	Chemical	D020123
+19356053	1805	1816	proteinuria	Disease	D011507
+19356053	1831	1840	Sirolimus	Chemical	D020123
+19356053	1876	1887	proteinuria	Disease	D011507
+19356053	1946	1957	Proteinuria	Disease	D011507
+19356053	1998	2007	sirolimus	Chemical	D020123
+19356053	CID	D020123	D011507
+
+19729346|t|Comparative cognitive and subjective side effects of immediate-release oxycodone in healthy middle-aged and older adults.
+19729346|a|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.
+19729346	71	80	oxycodone	Chemical	D010098
+19729346	238	247	oxycodone	Chemical	D010098
+19729346	377	381	pain	Disease	D010146
+19729346	495	504	oxycodone	Chemical	D010098
+19729346	514	523	oxycodone	Chemical	D010098
+19729346	738	815	declines in simple and sustained attention, working memory, and verbal memory	Disease	D003072|D008569	declines in simple and sustained attention|declines in working memory, and verbal memory
+19729346	1210	1222	chronic pain	Disease	D059350
+19729346	1316	1325	oxycodone	Chemical	D010098
+19729346	1496	1505	oxycodone	Chemical	D010098
+19729346	CID	D010098	D008569
+19729346	CID	D010098	D003072
+
+20080983|t|Normalizing effects of modafinil on sleep in chronic cocaine users.
+20080983|a|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.
+20080983	23	32	modafinil	Chemical	C048833
+20080983	53	60	cocaine	Chemical	D003042
+20080983	157	166	modafinil	Chemical	C048833
+20080983	180	198	daytime sleepiness	Disease	D012893
+20080983	210	217	cocaine	Chemical	D003042
+20080983	240	247	cocaine	Chemical	D003042
+20080983	305	314	modafinil	Chemical	C048833
+20080983	919	926	cocaine	Chemical	D003042
+20080983	1029	1038	modafinil	Chemical	C048833
+20080983	1111	1118	cocaine	Chemical	D003042
+20080983	1157	1166	modafinil	Chemical	C048833
+20080983	1389	1396	cocaine	Chemical	D003042
+20080983	1465	1474	modafinil	Chemical	C048833
+20080983	1478	1485	cocaine	Chemical	D003042
+20080983	1510	1519	Modafinil	Chemical	C048833
+20080983	1669	1687	daytime sleepiness	Disease	D012893
+20080983	1716	1725	modafinil	Chemical	C048833
+20080983	1797	1815	daytime sleepiness	Disease	D012893
+20080983	1829	1836	cocaine	Chemical	D003042
+20080983	1894	1901	cocaine	Chemical	D003042
+20080983	CID	D003042	D012893
+
+20520283|t|Efficacy and safety of asenapine in a placebo- and haloperidol-controlled trial in patients with acute exacerbation of schizophrenia.
+20520283|a|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.
+20520283	23	32	asenapine	Chemical	C522667
+20520283	51	62	haloperidol	Chemical	D006220
+20520283	119	132	schizophrenia	Disease	D012559
+20520283	134	143	Asenapine	Chemical	C522667
+20520283	226	239	schizophrenia	Disease	D012559
+20520283	246	251	manic	Disease	D001714
+20520283	286	304	bipolar I disorder	Disease	D001714
+20520283	321	330	psychotic	Disease	D011618
+20520283	397	410	schizophrenia	Disease	D012559
+20520283	463	472	asenapine	Chemical	C522667
+20520283	500	509	asenapine	Chemical	C522667
+20520283	536	547	haloperidol	Chemical	D006220
+20520283	761	770	asenapine	Chemical	C522667
+20520283	795	806	haloperidol	Chemical	D006220
+20520283	950	959	asenapine	Chemical	C522667
+20520283	1015	1026	haloperidol	Chemical	D006220
+20520283	1194	1203	asenapine	Chemical	C522667
+20520283	1423	1432	asenapine	Chemical	C522667
+20520283	1453	1464	haloperidol	Chemical	D006220
+20520283	1500	1523	Extrapyramidal symptoms	Disease	D001480
+20520283	1585	1594	asenapine	Chemical	C522667
+20520283	1615	1626	haloperidol	Chemical	D006220
+20520283	1810	1819	asenapine	Chemical	C522667
+20520283	1824	1835	haloperidol	Chemical	D006220
+20520283	1884	1907	extrapyramidal symptoms	Disease	D001480
+20520283	CID	D006220	D001480
+20520283	CID	C522667	D001480
+
+20588063|t|Permeability, ultrastructural changes, and distribution of novel proteins in the glomerular barrier in early puromycin aminonucleoside nephrosis.
+20588063|a|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.
+20588063	109	134	puromycin aminonucleoside	Chemical	D011692
+20588063	135	144	nephrosis	Disease	D009401
+20588063	219	230	proteinuria	Disease	D011507
+20588063	245	270	puromycin aminonucleoside	Chemical	D011692
+20588063	271	280	nephrosis	Disease	D009401
+20588063	816	827	proteinuria	Disease	D011507
+20588063	1036	1047	proteinuria	Disease	D011507
+20588063	1357	1368	proteinuria	Disease	D011507
+20588063	CID	D011692	D011507
+20588063	CID	D011692	D009401
+
+19820426|t|Twin preterm neonates with cardiac toxicity related to lopinavir/ritonavir therapy.
+19820426|a|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.
+19820426	27	43	cardiac toxicity	Disease	D066126
+19820426	55	74	lopinavir/ritonavir	Chemical	C558899
+19820426	176	214	human immunodeficiency virus infection	Disease	D015658
+19820426	252	263	heart block	Disease	D006327
+19820426	268	290	dilated cardiomyopathy	Disease	D002311
+19820426	302	321	lopinavir/ritonavir	Chemical	C558899
+19820426	403	414	bradycardia	Disease	D001919
+19820426	451	470	lopinavir/ritonavir	Chemical	C558899
+19820426	CID	C558899	D002311
+19820426	CID	C558899	D006327
+19820426	CID	C558899	D001919
+
+1616457|t|Learning of rats under amnesia caused by pentobarbital.
+1616457|a|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.
+1616457	23	30	amnesia	Disease	D000647
+1616457	41	54	pentobarbital	Chemical	D010424
+1616457	122	129	amnesia	Disease	D000647
+1616457	142	155	pentobarbital	Chemical	D010424
+1616457	322	335	pentobarbital	Chemical	D010424
+1616457	492	511	memory dissociation	Disease	D008569
+1616457	602	615	pentobarbital	Chemical	D010424
+1616457	718	731	pentobarbital	Chemical	D010424
+1616457	CID	D010424	D000647
+
+567256|t|Angiosarcoma of the liver associated with diethylstilbestrol.
+567256|a|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.
+567256	0	25	Angiosarcoma of the liver	Disease	D006394|D008113	Angiosarcoma|Angiosarcoma of the liver
+567256	42	60	diethylstilbestrol	Chemical	D004054
+567256	62	87	Angiosarcoma of the liver	Disease	D006394|D008113	Angiosarcoma|Angiosarcoma of the liver
+567256	165	192	adenocarcinoma of the liver	Disease	D000230|D008113	adenocarcinoma|adenocarcinoma of the liver
+567256	198	216	diethylstilbestrol	Chemical	D004054
+567256	231	243	Angiosarcoma	Disease	D006394
+567256	323	344	intraarterial lesions	Disease	D014652
+567256	381	387	tumors	Disease	D009369
+567256	CID	D004054	D008113
+567256	CID	D004054	D006394
+
+17439425|t|Role of xanthine oxidase in dexamethasone-induced hypertension in rats.
+17439425|a|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.
+17439425	8	16	xanthine	Chemical	D019820
+17439425	28	41	dexamethasone	Chemical	D003907
+17439425	50	62	hypertension	Disease	D006973
+17439425	98	110	hypertension	Disease	D006973
+17439425	115	117	HT	Disease	D006973
+17439425	149	161	nitric oxide	Chemical	D009569
+17439425	205	213	xanthine	Chemical	D019820
+17439425	297	310	dexamethasone	Chemical	D003907
+17439425	319	331	hypertension	Disease	D006973
+17439425	333	336	dex	Chemical	D003907
+17439425	337	339	HT	Disease	D006973
+17439425	435	448	dexamethasone	Chemical	D003907
+17439425	450	453	dex	Chemical	D003907
+17439425	456	467	allopurinol	Chemical	D000493
+17439425	485	496	allopurinol	Chemical	D000493
+17439425	502	505	dex	Chemical	D003907
+17439425	664	669	urate	Chemical	D014527
+17439425	698	701	Dex	Chemical	D003907
+17439425	702	715	increased SBP	Disease	D006973
+17439425	758	802	decreased thymus (P < 0.001) and bodyweights	Disease	D015431
+17439425	816	827	Allopurinol	Chemical	D000493
+17439425	844	849	urate	Chemical	D014527
+17439425	954	957	dex	Chemical	D003907
+17439425	988	999	Allopurinol	Chemical	D000493
+17439425	1016	1019	dex	Chemical	D003907
+17439425	1020	1022	HT	Disease	D006973
+17439425	1071	1082	allopurinol	Chemical	D000493
+17439425	1138	1150	hypertension	Disease	D006973
+17439425	1211	1213	HT	Disease	D006973
+17439425	CID	D003907	D015431
+17439425	CID	D003907	D006973
+
+9351491|t|Extrapyramidal side effects with risperidone and haloperidol at comparable D2 receptor occupancy levels.
+9351491|a|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.
+9351491	33	44	risperidone	Chemical	D018967
+9351491	49	60	haloperidol	Chemical	D006220
+9351491	105	116	Risperidone	Chemical	D018967
+9351491	164	172	dopamine	Chemical	D004298
+9351491	180	195	serotonin 5-HT2	Chemical	D044348
+9351491	252	263	risperidone	Chemical	D018967
+9351491	331	349	psychotic symptoms	Disease	D011618
+9351491	486	497	risperidone	Chemical	D018967
+9351491	703	714	risperidone	Chemical	D018967
+9351491	727	738	haloperidol	Chemical	D006220
+9351491	753	764	risperidone	Chemical	D018967
+9351491	769	780	haloperidol	Chemical	D006220
+9351491	946	957	haloperidol	Chemical	D006220
+9351491	961	972	risperidone	Chemical	D018967
+9351491	974	999	Drug-induced parkinsonism	Disease	D010302
+9351491	1038	1049	risperidone	Chemical	D018967
+9351491	1060	1071	haloperidol	Chemical	D006220
+9351491	1205	1216	risperidone	Chemical	D018967
+9351491	CID	D018967	D010302
+9351491	CID	D006220	D010302
+
+18752389|t|Simvastatin-ezetimibe-induced hepatic failure necessitating liver transplantation.
+18752389|a|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.
+18752389	0	21	Simvastatin-ezetimibe	Chemical	C492458
+18752389	30	45	hepatic failure	Disease	D017093
+18752389	224	230	statin	Chemical	D019821
+18752389	250	261	hepatotoxic	Disease	D056486
+18752389	305	314	ezetimibe	Chemical	C108606
+18752389	340	361	simvastatin-ezetimibe	Chemical	C492458
+18752389	418	443	fulminant hepatic failure	Disease	D017114
+18752389	511	522	simvastatin	Chemical	D019821
+18752389	536	569	simvastatin 10 mg-ezetimibe 40 mg	Chemical	C492458
+18752389	626	637	simvastatin	Chemical	D019821
+18752389	694	708	hepatotoxicity	Disease	D056486
+18752389	814	834	Simvastatinezetimibe	Chemical	C492458
+18752389	839	851	escitalopram	Chemical	D015283
+18752389	878	888	depression	Disease	D003866
+18752389	939	953	hepatotoxicity	Disease	D056486
+18752389	1099	1112	drug toxicity	Disease	D064420
+18752389	1314	1323	Ezetimibe	Chemical	C108606
+18752389	1363	1382	uridine diphosphate	Chemical	D014530
+18752389	1487	1511	simvastatin hydroxy acid	Chemical	C532833
+18752389	1536	1547	simvastatin	Chemical	D019821
+18752389	1572	1586	hepatotoxicity	Disease	D056486
+18752389	1639	1660	simvastatin-ezetimibe	Chemical	C492458
+18752389	1669	1682	liver failure	Disease	D017093
+18752389	1762	1782	simvastatinezetimibe	Chemical	C492458
+18752389	1791	1805	hepatotoxicity	Disease	D056486
+18752389	1823	1834	simvastatin	Chemical	D019821
+18752389	1847	1856	ezetimibe	Chemical	C108606
+18752389	1924	1938	hepatotoxicity	Disease	D056486
+18752389	1944	1965	simvastatin-ezetimibe	Chemical	C492458
+18752389	CID	C492458	D056486
+18752389	CID	C492458	D017114
+
+20098969|t|Oral manifestations of "meth mouth": a case report.
+20098969|a|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.
+20098969	24	34	meth mouth	Disease	-1
+20098969	140	150	meth mouth	Disease	-1
+20098969	226	241	Methamphetamine	Chemical	D008694
+20098969	369	389	cardiac dysrhythmias	Disease	D001145
+20098969	391	403	hypertension	Disease	D006973
+20098969	405	419	hallucinations	Disease	D006212
+20098969	425	441	violent behavior	Disease	D001523
+20098969	467	482	methamphetamine	Chemical	D008694
+20098969	519	529	xerostomia	Disease	D014987
+20098969	539	545	caries	Disease	D003731
+20098969	548	558	meth mouth	Disease	-1
+20098969	576	586	tooth wear	Disease	D057085
+20098969	626	641	methamphetamine	Chemical	D008694
+20098969	732	736	pain	Disease	D010146
+20098969	738	748	bad breath	Disease	D012120
+20098969	903	918	carious lesions	Disease	D003731
+20098969	990	1005	methamphetamine	Chemical	D008694
+20098969	1055	1071	carious episodes	Disease	D003731
+20098969	1229	1239	meth mouth	Disease	-1
+20098969	1510	1520	meth mouth	Disease	-1
+20098969	1613	1629	methamphetamines	Chemical	D008694
+20098969	CID	D008694	D003731
+
+9653867|t|Thyroxine abuse: an unusual case of thyrotoxicosis in pregnancy.
+9653867|a|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.
+9653867	0	9	Thyroxine	Chemical	D013974
+9653867	36	50	thyrotoxicosis	Disease	D013971
+9653867	65	81	Eating disorders	Disease	D001068
+9653867	126	136	drug abuse	Disease	D019966
+9653867	381	397	eating disorders	Disease	D001068
+9653867	583	599	eating disorders	Disease	D001068
+9653867	637	651	thyrotoxicosis	Disease	D013971
+9653867	669	678	thyroxine	Chemical	D013974
+9653867	CID	D013974	D013971
+
+17608141|t|Attenuation of methamphetamine-induced nigrostriatal dopaminergic neurotoxicity in mice by lipopolysaccharide pretreatment.
+17608141|a|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.
+17608141	15	30	methamphetamine	Chemical	D008694
+17608141	66	79	neurotoxicity	Disease	D020258
+17608141	91	109	lipopolysaccharide	Chemical	D008070
+17608141	185	200	methamphetamine	Chemical	D008694
+17608141	209	237	dopaminergic terminal damage	Disease	D009422
+17608141	279	297	lipopolysaccharide	Chemical	D008070
+17608141	371	386	methamphetamine	Chemical	D008694
+17608141	409	417	dopamine	Chemical	D004298
+17608141	418	431	neurotoxicity	Disease	D020258
+17608141	433	451	Lipopolysaccharide	Chemical	D008070
+17608141	510	525	methamphetamine	Chemical	D008694
+17608141	535	547	hyperthermia	Disease	D005334
+17608141	580	598	lipopolysaccharide	Chemical	D008070
+17608141	619	634	methamphetamine	Chemical	D008694
+17608141	652	660	dopamine	Chemical	D004298
+17608141	665	695	3,4-dihydroxyphenylacetic acid	Chemical	D015102
+17608141	772	790	lipopolysaccharide	Chemical	D008070
+17608141	847	862	methamphetamine	Chemical	D008694
+17608141	879	894	methamphetamine	Chemical	D008694
+17608141	912	920	dopamine	Chemical	D004298
+17608141	925	955	3,4-dihydroxyphenylacetic acid	Chemical	D015102
+17608141	1006	1024	lipopolysaccharide	Chemical	D008070
+17608141	1065	1080	methamphetamine	Chemical	D008694
+17608141	1099	1107	dopamine	Chemical	D004298
+17608141	1112	1142	3,4-dihydroxyphenylacetic acid	Chemical	D015102
+17608141	1212	1230	lipopolysaccharide	Chemical	D008070
+17608141	1306	1321	methamphetamine	Chemical	D008694
+17608141	1372	1390	lipopolysaccharide	Chemical	D008070
+17608141	1445	1460	methamphetamine	Chemical	D008694
+17608141	1483	1491	dopamine	Chemical	D004298
+17608141	1492	1505	neurotoxicity	Disease	D020258
+17608141	CID	D008694	D005334
+
+2559236|t|Effect of converting enzyme inhibition on the course of adriamycin-induced nephropathy.
+2559236|a|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)
+2559236	56	66	adriamycin	Chemical	D004317
+2559236	75	86	nephropathy	Disease	D007674
+2559236	140	149	enalapril	Chemical	D004656
+2559236	202	212	adriamycin	Chemical	D004317
+2559236	213	222	nephrosis	Disease	D009401
+2559236	257	267	adriamycin	Chemical	D004317
+2559236	325	336	albuminuria	Disease	D000419
+2559236	452	461	enalapril	Chemical	D004656
+2559236	562	571	enalapril	Chemical	D004656
+2559236	768	779	albuminuria	Disease	D000419
+2559236	942	951	enalapril	Chemical	D004656
+2559236	970	982	renal injury	Disease	D007674
+2559236	986	996	adriamycin	Chemical	D004317
+2559236	997	1006	nephrosis	Disease	D009401
+2559236	1016	1025	enalapril	Chemical	D004656
+2559236	1076	1087	albuminuria	Disease	D000419
+2559236	1234	1243	Enalapril	Chemical	D004656
+2559236	1471	1491	glomerular sclerosis	Disease	D007674
+2559236	CID	D004317	D000419
+2559236	CID	D004317	D009401
+
+21029050|t|Butyrylcholinesterase gene mutations in patients with prolonged apnea after succinylcholine for electroconvulsive therapy.
+21029050|a|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.
+21029050	64	69	apnea	Disease	D001049
+21029050	76	91	succinylcholine	Chemical	D013390
+21029050	201	216	succinylcholine	Chemical	D013390
+21029050	600	615	succinylcholine	Chemical	D013390
+21029050	847	852	apnea	Disease	D001049
+21029050	960	965	apnea	Disease	D001049
+21029050	1138	1143	apnea	Disease	D001049
+21029050	1391	1406	succinylcholine	Chemical	D013390
+21029050	1500	1505	apnea	Disease	D001049
+21029050	CID	D013390	D001049
+
+10901305|t|Ketamine sedation for the reduction of children's fractures in the emergency department.
+10901305|a|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.
+10901305	0	8	Ketamine	Chemical	D007649
+10901305	50	59	fractures	Disease	D050723
+10901305	160	168	ketamine	Chemical	D007649
+10901305	322	330	ketamine	Chemical	D007649
+10901305	375	384	fractures	Disease	D050723
+10901305	578	586	fracture	Disease	D050723
+10901305	590	601	dislocation	Disease	D004204
+10901305	643	649	trauma	Disease	D014947
+10901305	687	709	Ketamine hydrochloride	Chemical	D007649
+10901305	1102	1106	pain	Disease	D010146
+10901305	1242	1246	Pain	Disease	D010146
+10901305	1324	1332	ketamine	Chemical	D007649
+10901305	1356	1364	fracture	Disease	D050723
+10901305	1368	1379	dislocation	Disease	D004204
+10901305	1686	1690	Pain	Disease	D010146
+10901305	1762	1766	pain	Disease	D010146
+10901305	1774	1782	fracture	Disease	D050723
+10901305	1803	1811	fracture	Disease	D050723
+10901305	2204	2210	nausea	Disease	D009325
+10901305	2232	2238	emesis	Disease	D014839
+10901305	2276	2282	nausea	Disease	D009325
+10901305	2285	2295	clumsiness	Disease	D001259
+10901305	2308	2324	ataxic movements	Disease	D001259
+10901305	2347	2365	dysphoric reaction	Disease	-1
+10901305	2435	2449	hallucinations	Disease	D006212
+10901305	2478	2486	Ketamine	Chemical	D007649
+10901305	2598	2607	fractures	Disease	D050723
+10901305	2656	2664	Ketamine	Chemical	D007649
+10901305	CID	D007649	D009325
+10901305	CID	D007649	D014839
+10901305	CID	D007649	D001259
+
+19037603|t|Prophylactic use of lamivudine with chronic immunosuppressive therapy for rheumatologic disorders.
+19037603|a|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.
+19037603	20	30	lamivudine	Chemical	D019259
+19037603	74	97	rheumatologic disorders	Disease	D012216
+19037603	223	233	lamivudine	Chemical	D019259
+19037603	237	270	hepatitis B virus surface antigen	Chemical	D006514
+19037603	272	278	HBs Ag	Chemical	D006514
+19037603	303	324	rheumatologic disease	Disease	D012216
+19037603	361	367	HBs Ag	Chemical	D006514
+19037603	391	413	rheumatologic diseases	Disease	D012216
+19037603	467	477	lamivudine	Chemical	D019259
+19037603	542	553	hepatitis B	Disease	D006509
+19037603	888	898	Lamivudine	Chemical	D019259
+19037603	1279	1302	abnormal liver function	Disease	D056486
+19037603	1584	1594	Lamivudine	Chemical	D019259
+19037603	1680	1690	lamivudine	Chemical	D019259
+19037603	CID	D006514	D006509
+
+20084309|t|Safety of transesophageal echocardiography in adults: study in a multidisciplinary hospital.
+20084309|a|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.
+20084309	303	312	Midazolan	Chemical	D008874
+20084309	314	316	MZ	Chemical	D008874
+20084309	322	332	Flumazenil	Chemical	D005442
+20084309	334	336	FL	Chemical	D005442
+20084309	469	471	MZ	Chemical	D008874
+20084309	595	597	MZ	Chemical	D008874
+20084309	726	732	stroke	Disease	D020521
+20084309	734	748	myocardiopathy	Disease	D009202
+20084309	750	752	MP	Disease	D009202
+20084309	777	797	mitral regurgitation	Disease	D008944
+20084309	799	801	MR	Disease	D008944
+20084309	811	813	MZ	Chemical	D008874
+20084309	911	913	MZ	Chemical	D008874
+20084309	918	920	FL	Chemical	D005442
+20084309	1096	1103	hypoxia	Disease	D000860
+20084309	1191	1198	hypoxia	Disease	D000860
+20084309	1212	1230	airway obstruction	Disease	D000402
+20084309	1273	1280	hypoxia	Disease	D000860
+20084309	1291	1293	MZ	Chemical	D008874
+20084309	1309	1320	hypotension	Disease	D007022
+20084309	1409	1411	MR	Disease	D008944
+20084309	1413	1415	MP	Disease	D009202
+20084309	1443	1445	MZ	Chemical	D008874
+20084309	1526	1528	MP	Disease	D009202
+20084309	1562	1564	MR	Disease	D008944
+20084309	CID	D008874	D000860
+
+8231633|t|Effects of calcium channel blockers on bupivacaine-induced toxicity.
+8231633|a|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.
+8231633	11	18	calcium	Chemical	D002118
+8231633	39	50	bupivacaine	Chemical	D002045
+8231633	59	67	toxicity	Disease	D064420
+8231633	131	138	calcium	Chemical	D002118
+8231633	159	170	bupivacaine	Chemical	D002045
+8231633	185	193	toxicity	Disease	D064420
+8231633	224	231	calcium	Chemical	D002118
+8231633	250	259	diltiazem	Chemical	D004110
+8231633	261	270	verapamil	Chemical	D014700
+8231633	275	283	bepridil	Chemical	D015764
+8231633	510	521	bupivacaine	Chemical	D002045
+8231633	722	729	calcium	Chemical	D002118
+8231633	775	786	bupivacaine	Chemical	D002045
+8231633	822	829	calcium	Chemical	D002118
+8231633	887	898	bupivacaine	Chemical	D002045
+8231633	907	918	convulsions	Disease	D012640
+8231633	957	965	bepridil	Chemical	D015764
+8231633	CID	D002045	D012640
+
+10091617|t|Selegiline-induced postural hypotension in Parkinson's disease: a longitudinal study on the effects of drug withdrawal.
+10091617|a|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.
+10091617	0	10	Selegiline	Chemical	D012642
+10091617	19	39	postural hypotension	Disease	D007024
+10091617	43	62	Parkinson's disease	Disease	D010300
+10091617	151	170	Parkinson's Disease	Disease	D010300
+10091617	247	266	Parkinson's disease	Disease	D010300
+10091617	268	270	PD	Disease	D010300
+10091617	300	310	selegiline	Chemical	D012642
+10091617	323	329	L-dopa	Chemical	D007980
+10091617	357	363	L-dopa	Chemical	D007980
+10091617	408	418	selegiline	Chemical	D012642
+10091617	423	429	L-dopa	Chemical	D007980
+10091617	460	492	systolic orthostatic hypotension	Disease	D007024
+10091617	530	540	selegiline	Chemical	D012642
+10091617	816	826	selegiline	Chemical	D012642
+10091617	916	939	orthostatic hypotension	Disease	D007024
+10091617	1035	1037	PD	Disease	D010300
+10091617	1057	1067	selegiline	Chemical	D012642
+10091617	1128	1160	systolic orthostatic hypotension	Disease	D007024
+10091617	1191	1193	PD	Disease	D010300
+10091617	1206	1216	selegiline	Chemical	D012642
+10091617	1303	1326	orthostatic hypotension	Disease	D007024
+10091617	1351	1374	Orthostatic hypotension	Disease	D007024
+10091617	1418	1428	selegiline	Chemical	D012642
+10091617	1502	1512	selegiline	Chemical	D012642
+10091617	1532	1589	reduced the supine systolic and diastolic blood pressures	Disease	D007024
+10091617	1712	1722	selegiline	Chemical	D012642
+10091617	1743	1749	L-dopa	Chemical	D007980
+10091617	1779	1802	orthostatic hypotension	Disease	D007024
+10091617	1932	1943	amphetamine	Chemical	D000661
+10091617	1948	1962	metamphetamine	Chemical	D008694
+10091617	CID	D012642	D007024
+
+19269743|t|Explicit episodic memory for sensory-discriminative components of capsaicin-induced pain: immediate and delayed ratings.
+19269743|a|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.
+19269743	66	75	capsaicin	Chemical	D002211
+19269743	84	88	pain	Disease	D010146
+19269743	121	125	Pain	Disease	D010146
+19269743	161	165	pain	Disease	D010146
+19269743	210	214	pain	Disease	D010146
+19269743	320	324	pain	Disease	D010146
+19269743	367	371	pain	Disease	D010146
+19269743	459	468	capsaicin	Chemical	D002211
+19269743	611	615	Pain	Disease	D010146
+19269743	801	806	pains	Disease	D010146
+19269743	823	832	Capsaicin	Chemical	D002211
+19269743	962	966	pain	Disease	D010146
+19269743	1055	1059	pain	Disease	D010146
+19269743	1090	1099	capsaicin	Chemical	D002211
+19269743	1224	1228	Pain	Disease	D010146
+19269743	1618	1622	pain	Disease	D010146
+19269743	CID	D002211	D010146
+
+3070035|t|Reversibility of captopril-induced renal insufficiency after prolonged use in an unusual case of renovascular hypertension.
+3070035|a|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.
+3070035	17	26	captopril	Chemical	D002216
+3070035	35	54	renal insufficiency	Disease	D051437
+3070035	97	122	renovascular hypertension	Disease	D006978
+3070035	151	163	hypertension	Disease	D006973
+3070035	230	268	sudden deterioration of renal function	Disease	D058186
+3070035	294	303	captopril	Chemical	D002216
+3070035	384	393	captopril	Chemical	D002216
+3070035	497	506	captopril	Chemical	D002216
+3070035	515	528	renal failure	Disease	D051437
+3070035	CID	D002216	D058186
+
+1147734|t|Liver disease caused by propylthiouracil.
+1147734|a|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.
+1147734	0	13	Liver disease	Disease	D008107
+1147734	24	40	propylthiouracil	Chemical	D011441
+1147734	155	192	chronic active (aggressive) hepatitis	Disease	D006521
+1147734	225	241	propylthiouracil	Chemical	D011441
+1147734	337	350	liver disease	Disease	D008107
+1147734	CID	D011441	D006521
+
+12202650|t|Capsaicin-induced muscle pain alters the excitability of the human jaw-stretch reflex.
+12202650|a|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.
+12202650	0	9	Capsaicin	Chemical	D002211
+12202650	18	29	muscle pain	Disease	D063806
+12202650	118	145	temporomandibular disorders	Disease	D013705
+12202650	198	209	muscle pain	Disease	D063806
+12202650	311	329	nociceptive muscle	Disease	D063806
+12202650	506	515	Capsaicin	Chemical	D002211
+12202650	577	581	pain	Disease	D010146
+12202650	784	788	pain	Disease	D010146
+12202650	1022	1026	pain	Disease	D010146
+12202650	1064	1078	painful muscle	Disease	D063806
+12202650	1139	1150	muscle pain	Disease	D063806
+12202650	CID	D002211	D010146
+
+18951540|t|Repetitive transcranial magnetic stimulation for levodopa-induced dyskinesias in Parkinson's disease.
+18951540|a|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.
+18951540	49	57	levodopa	Chemical	D007980
+18951540	66	77	dyskinesias	Disease	D004409
+18951540	81	100	Parkinson's disease	Disease	D010300
+18951540	287	298	dyskinesias	Disease	D004409
+18951540	316	335	Parkinson's disease	Disease	D010300
+18951540	337	339	PD	Disease	D010300
+18951540	360	362	PD	Disease	D010300
+18951540	377	388	dyskinesias	Disease	D004409
+18951540	744	754	dyskinesia	Disease	D004409
+18951540	845	855	dyskinesia	Disease	D004409
+18951540	926	934	dystonia	Disease	D004421
+18951540	1032	1042	dyskinesia	Disease	D004409
+18951540	1243	1245	PD	Disease	D010300
+18951540	1405	1416	dyskinesias	Disease	D004409
+18951540	1420	1422	PD	Disease	D010300
+18951540	CID	D007980	D004409
+
+19657887|t|Disulfiram-like syndrome after hydrogen cyanamide professional skin exposure: two case reports in France.
+19657887|a|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.
+19657887	0	10	Disulfiram	Chemical	D004221
+19657887	31	49	hydrogen cyanamide	Chemical	D003484
+19657887	106	124	Hydrogen cyanamide	Chemical	D003484
+19657887	300	308	aldehyde	Chemical	D000079
+19657887	338	350	acetaldehyde	Chemical	D000079
+19657887	371	378	alcohol	Chemical	D000431
+19657887	441	451	disulfiram	Chemical	D004221
+19657887	501	519	hydrogen cyanamide	Chemical	D003484
+19657887	572	578	Dormex	Chemical	D003484
+19657887	595	613	hydrogen cyanamide	Chemical	D003484
+19657887	668	675	alcohol	Chemical	D000431
+19657887	734	741	alcohol	Chemical	D000431
+19657887	769	789	flushing of the face	Disease	D005483
+19657887	791	802	tachycardia	Disease	D013610
+19657887	808	815	dyspnea	Disease	D004417
+19657887	974	980	Dormex	Chemical	D003484
+19657887	1022	1032	disulfiram	Chemical	D004221
+19657887	1052	1060	flushing	Disease	D005483
+19657887	1062	1073	tachycardia	Disease	D013610
+19657887	1079	1099	arterial hypotension	Disease	D007022
+19657887	1268	1275	alcohol	Chemical	D000431
+19657887	1334	1340	Dormex	Chemical	D003484
+19657887	CID	D000431	D007022
+19657887	CID	D000431	D005483
+19657887	CID	D003484	D007022
+19657887	CID	D000431	D004417
+19657887	CID	D003484	D013610
+19657887	CID	D003484	D004417
+19657887	CID	D000431	D013610
+19657887	CID	D003484	D005483
+
+9660111|t|Repeated trimipramine induces dopamine D2/D3 and alpha1-adrenergic up-regulation.
+9660111|a|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.
+9660111	9	21	trimipramine	Chemical	D014299
+9660111	30	38	dopamine	Chemical	D004298
+9660111	82	94	Trimipramine	Chemical	D014299
+9660111	96	99	TRI	Chemical	D014299
+9660111	125	139	antidepressant	Chemical	D000928
+9660111	175	185	imipramine	Chemical	D007099
+9660111	223	236	noradrenaline	Chemical	D009638
+9660111	241	260	5-hydroxytryptamine	Chemical	D012701
+9660111	335	349	antidepressant	Chemical	D000928
+9660111	430	433	TRI	Chemical	D014299
+9660111	580	595	antidepressants	Chemical	D000928
+9660111	597	600	TRI	Chemical	D014299
+9660111	717	720	TRI	Chemical	D014299
+9660111	758	767	reserpine	Chemical	D012110
+9660111	768	779	hypothermia	Disease	D007035
+9660111	816	835	5-hydroxytryptophan	Chemical	D006916
+9660111	859	862	TRI	Chemical	D014299
+9660111	912	925	hyperactivity	Disease	D006948
+9660111	937	950	d-amphetamine	Chemical	D003913
+9660111	952	962	quinpirole	Chemical	D019257
+9660111	1005	1013	dopamine	Chemical	D004298
+9660111	1062	1075	d-amphetamine	Chemical	D003913
+9660111	1079	1090	apomorphine	Chemical	D001058
+9660111	1114	1117	TRI	Chemical	D014299
+9660111	1168	1181	phenylephrine	Chemical	D010656
+9660111	1266	1280	aggressiveness	Disease	D010554
+9660111	1291	1300	clonidine	Chemical	D003000
+9660111	1425	1440	antidepressants	Chemical	D000928
+9660111	1461	1464	TRI	Chemical	D014299
+9660111	1520	1528	dopamine	Chemical	D004298
+9660111	1752	1767	antidepressants	Chemical	D000928
+9660111	1805	1819	antidepressant	Chemical	D000928
+9660111	CID	D003913	D006948
+9660111	CID	D012110	D007035
+9660111	CID	D014299	D006948
+9660111	CID	D019257	D006948
+
+11431197|t|Ranitidine-induced acute interstitial nephritis in a cadaveric renal allograft.
+11431197|a|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.
+11431197	0	10	Ranitidine	Chemical	D011899
+11431197	25	47	interstitial nephritis	Disease	D009395
+11431197	80	90	Ranitidine	Chemical	D011899
+11431197	226	248	interstitial nephritis	Disease	D009395
+11431197	345	355	ranitidine	Chemical	D011899
+11431197	370	392	interstitial nephritis	Disease	D009395
+11431197	CID	D011899	D009395
+
+7449470|t|Late, late doxorubicin cardiotoxicity.
+7449470|a|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.
+7449470	11	22	doxorubicin	Chemical	D004317
+7449470	23	37	cardiotoxicity	Disease	D066126
+7449470	39	55	Cardiac toxicity	Disease	D066126
+7449470	104	114	adriamycin	Chemical	D004317
+7449470	144	158	Cardiomyopathy	Disease	D009202
+7449470	321	335	cardiomyopathy	Disease	D009202
+7449470	424	438	cardiotoxicity	Disease	D066126
+7449470	CID	D004317	D009202
+
+8170551|t|Acetazolamide-induced nephrolithiasis: implications for treatment of neuromuscular disorders.
+8170551|a|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.
+8170551	0	13	Acetazolamide	Chemical	D000086
+8170551	22	37	nephrolithiasis	Disease	D053040
+8170551	69	92	neuromuscular disorders	Disease	D009468
+8170551	134	149	nephrolithiasis	Disease	D053040
+8170551	246	255	paralysis	Disease	D010243
+8170551	260	268	myotonia	Disease	D009222
+8170551	288	301	acetazolamide	Chemical	D000086
+8170551	318	331	renal calculi	Disease	D007669
+8170551	383	397	renal calculus	Disease	D007669
+8170551	444	452	calculus	Disease	D002137
+8170551	545	560	Nephrolithiasis	Disease	D053040
+8170551	582	595	acetazolamide	Chemical	D000086
+8170551	CID	D000086	D007669
+
+2476560|t|Is the treatment of scabies hazardous?
+2476560|a|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.
+2476560	20	27	scabies	Disease	D012532
+2476560	53	60	scabies	Disease	D012532
+2476560	122	129	lindane	Chemical	D001556
+2476560	131	157	gamma benzene hexachloride	Chemical	D001556
+2476560	184	191	Lindane	Chemical	D001556
+2476560	361	368	lindane	Chemical	D001556
+2476560	376	411	toxic to the central nervous system	Disease	D002493
+2476560	439	455	aplastic anaemia	Disease	D000741
+2476560	481	488	lindane	Chemical	D001556
+2476560	767	775	toxicity	Disease	D064420
+2476560	CID	D001556	D000741
+2476560	CID	D001556	D002493
+
+19803309|t|Anaesthetists' nightmare: masseter spasm after induction in an undiagnosed case of myotonia congenita.
+19803309|a|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.
+19803309	26	40	masseter spasm	Disease	D014313
+19803309	83	101	myotonia congenita	Disease	D009224
+19803309	136	154	myotonia congenita	Disease	D009224
+19803309	236	250	masseter spasm	Disease	D014313
+19803309	292	305	suxamethonium	Chemical	D013390
+19803309	CID	D013390	D014313
+
+18821488|t|Toxicity in rhesus monkeys following administration of the 8-aminoquinoline 8-[(4-amino-l-methylbutyl)amino]- 5-(l-hexyloxy)-6-methoxy-4-methylquinoline (WR242511).
+18821488|a|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.
+18821488	0	8	Toxicity	Disease	D064420
+18821488	59	75	8-aminoquinoline	Chemical	C080436
+18821488	76	152	8-[(4-amino-l-methylbutyl)amino]- 5-(l-hexyloxy)-6-methoxy-4-methylquinoline	Chemical	C068820
+18821488	154	162	WR242511	Chemical	C068820
+18821488	258	266	toxicity	Disease	D064420
+18821488	332	341	poisoning	Disease	D011041
+18821488	462	478	8-aminoquinoline	Chemical	C080436
+18821488	479	487	WR242511	Chemical	C068820
+18821488	664	672	WR242511	Chemical	C068820
+18821488	809	817	WR242511	Chemical	C068820
+18821488	939	947	WR242511	Chemical	C068820
+18821488	976	993	methemoglobinemia	Disease	D008708
+18821488	1133	1147	hemoglobinuria	Disease	D006456
+18821488	1200	1208	WR242511	Chemical	C068820
+18821488	1306	1319	Myoglobinuria	Disease	D009212
+18821488	1428	1453	liver and kidney toxicity	Disease	D056486|D007674	liver toxicity|kidney toxicity
+18821488	1579	1587	toxicity	Disease	D064420
+18821488	1610	1618	WR242511	Chemical	C068820
+18821488	1666	1675	poisoning	Disease	D011041
+18821488	1793	1801	toxicity	Disease	D064420
+18821488	CID	C068820	D007674
+18821488	CID	C068820	D056486
+18821488	CID	C068820	D006456
+18821488	CID	C068820	D009212
+
+8372922|t|Neuroplasticity of the adult primate auditory cortex following cochlear hearing loss.
+8372922|a|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.
+8372922	72	84	hearing loss	Disease	D034381
+8372922	422	434	hearing loss	Disease	D034381
+8372922	709	718	kanamycin	Chemical	D007612
+8372922	723	733	furosemide	Chemical	D005665
+8372922	1238	1250	hearing loss	Disease	D034381
+8372922	CID	D005665	D034381
+8372922	CID	D007612	D034381
+
+9195768|t|The site of common side effects of sumatriptan.
+9195768|a|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.
+9195768	35	46	sumatriptan	Chemical	D018170
+9195768	48	67	Atypical sensations	Disease	D010292
+9195768	102	113	sumatriptan	Chemical	D018170
+9195768	278	308	tingling or burning sensations	Disease	D010292
+9195768	346	353	sunburn	Disease	D013471
+9195768	CID	D018170	D010292
+
+15338796|t|Tremor side effects of salbutamol, quantified by a laser pointer technique.
+15338796|a|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.
+15338796	0	6	Tremor	Disease	D014202
+15338796	23	33	salbutamol	Chemical	D000420
+15338796	96	102	tremor	Disease	D014202
+15338796	119	129	salbutamol	Chemical	D000420
+15338796	406	412	Tremor	Disease	D014202
+15338796	496	502	tremor	Disease	D014202
+15338796	523	547	obstructive lung disease	Disease	D008173
+15338796	592	602	salbutamol	Chemical	D000420
+15338796	879	885	tremor	Disease	D014202
+15338796	1008	1014	tremor	Disease	D014202
+15338796	1072	1078	tremor	Disease	D014202
+15338796	1128	1134	tremor	Disease	D014202
+15338796	1270	1276	Tremor	Disease	D014202
+15338796	1344	1354	Salbutamol	Chemical	D000420
+15338796	1379	1385	tremor	Disease	D014202
+15338796	1571	1577	tremor	Disease	D014202
+15338796	1619	1625	tremor	Disease	D014202
+15338796	1736	1742	tremor	Disease	D014202
+15338796	1774	1780	tremor	Disease	D014202
+15338796	1933	1939	tremor	Disease	D014202
+15338796	CID	D000420	D014202
+
+12627929|t|Increased frequency of venous thromboembolism with the combination of docetaxel and thalidomide in patients with metastatic androgen-independent prostate cancer.
+12627929|a|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.
+12627929	23	45	venous thromboembolism	Disease	D054556
+12627929	70	79	docetaxel	Chemical	C067311
+12627929	84	95	thalidomide	Chemical	D013792
+12627929	145	160	prostate cancer	Disease	D011471
+12627929	208	230	venous thromboembolism	Disease	D054556
+12627929	232	235	VTE	Disease	D054556
+12627929	284	299	prostate cancer	Disease	D011471
+12627929	322	331	docetaxel	Chemical	C067311
+12627929	361	372	thalidomide	Chemical	D013792
+12627929	578	593	prostate cancer	Disease	D011471
+12627929	650	659	docetaxel	Chemical	C067311
+12627929	761	772	thalidomide	Chemical	D013792
+12627929	808	817	docetaxel	Chemical	C067311
+12627929	896	904	toxicity	Disease	D064420
+12627929	993	1002	docetaxel	Chemical	C067311
+12627929	1019	1022	VTE	Disease	D054556
+12627929	1068	1077	docetaxel	Chemical	C067311
+12627929	1083	1094	thalidomide	Chemical	D013792
+12627929	1105	1108	VTE	Disease	D054556
+12627929	1148	1159	thalidomide	Chemical	D013792
+12627929	1163	1172	docetaxel	Chemical	C067311
+12627929	1193	1208	prostate cancer	Disease	D011471
+12627929	1250	1253	VTE	Disease	D054556
+12627929	1325	1336	thalidomide	Chemical	D013792
+12627929	CID	D013792	D054556
+12627929	CID	C067311	D054556
+
+6634932|t|Sublingual absorption of the quaternary ammonium antiarrhythmic agent, UM-272.
+6634932|a|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.
+6634932	29	48	quaternary ammonium	Chemical	D000644
+6634932	71	77	UM-272	Chemical	C002616
+6634932	79	85	UM-272	Chemical	C002616
+6634932	87	110	N,N-dimethylpropranolol	Chemical	C002616
+6634932	191	198	ouabain	Chemical	D010042
+6634932	207	231	ventricular tachycardias	Disease	D017180
+6634932	322	328	UM-272	Chemical	C002616
+6634932	339	362	ventricular tachycardia	Disease	D017180
+6634932	CID	D010042	D017180
+
+18791946|t|Severe thrombocytopenia and haemolytic anaemia associated with ciprofloxacin: a case report with fatal outcome.
+18791946|a|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.
+18791946	7	23	thrombocytopenia	Disease	D013921
+18791946	28	46	haemolytic anaemia	Disease	D000743
+18791946	63	76	ciprofloxacin	Chemical	D002939
+18791946	206	219	ciprofloxacin	Chemical	D002939
+18791946	263	277	abdominal pain	Disease	D015746
+18791946	282	290	jaundice	Disease	D007565
+18791946	326	339	ciprofloxacin	Chemical	D002939
+18791946	357	380	urinary tract infection	Disease	D014552
+18791946	444	460	thrombocytopenia	Disease	D013921
+18791946	465	475	haemolysis	Disease	D006461
+18791946	513	522	petechiae	Disease	D011693
+18791946	527	534	purpura	Disease	D011693
+18791946	758	770	haemorrhages	Disease	D006470
+18791946	784	806	bone marrow depression	Disease	D001855
+18791946	822	829	thrombi	Disease	D013927
+18791946	842	859	microangiopathies	Disease	D014652
+18791946	983	996	ciprofloxacin	Chemical	D002939
+18791946	1030	1046	thrombocytopenia	Disease	D013921
+18791946	1051	1069	haemolytic anaemia	Disease	D000743
+18791946	CID	D002939	D011693
+18791946	CID	D002939	D007565
+18791946	CID	D002939	D013921
+18791946	CID	D002939	D000743
+18791946	CID	D002939	D015746
+
+17344566|t|Simvastatin-induced bilateral leg compartment syndrome and myonecrosis associated with hypothyroidism.
+17344566|a|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.
+17344566	0	11	Simvastatin	Chemical	D019821
+17344566	34	54	compartment syndrome	Disease	D003161
+17344566	59	70	myonecrosis	Disease	D009135
+17344566	87	101	hypothyroidism	Disease	D007037
+17344566	117	128	hypothyroid	Disease	D007037
+17344566	141	150	thyroxine	Chemical	D013974
+17344566	155	166	simvastatin	Chemical	D019821
+17344566	196	216	compartment syndrome	Disease	D003161
+17344566	221	232	myonecrosis	Disease	D009135
+17344566	336	347	simvastatin	Chemical	D019821
+17344566	480	493	arteriopathic	Disease	D014652
+17344566	CID	D019821	D003161
+
+9293063|t|Bile duct hamartoma occurring in association with long-term treatment with danazol.
+9293063|a|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.
+9293063	0	19	Bile duct hamartoma	Disease	D001650|D006222	Bile duct hamartoma|hamartoma
+9293063	75	82	danazol	Chemical	D003613
+9293063	104	123	bile duct hamartoma	Disease	D001650|D006222	bile duct hamartoma|hamartoma
+9293063	179	186	danazol	Chemical	D003613
+9293063	333	343	liver mass	Disease	D008107
+9293063	CID	D003613	D001650
+9293063	CID	D003613	D006222
+
+1728522|t|Granulomatous hepatitis due to combination of amoxicillin and clavulanic acid.
+1728522|a|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.
+1728522	0	23	Granulomatous hepatitis	Disease	D006099|D056486	Granulomatous|hepatitis
+1728522	31	77	combination of amoxicillin and clavulanic acid	Chemical	D019980
+1728522	116	143	amoxicillin-clavulanic acid	Chemical	D019980
+1728522	152	161	hepatitis	Disease	D056486
+1728522	187	197	granulomas	Disease	D006099
+1728522	244	256	liver injury	Disease	D056486
+1728522	318	338	cholestatic syndrome	Disease	D002779
+1728522	359	369	granulomas	Disease	D006099
+1728522	374	386	eosinophilia	Disease	D004802
+1728522	425	435	penicillin	Chemical	D010406
+1728522	452	463	amoxicillin	Chemical	D000658
+1728522	517	528	amoxicillin	Chemical	D000658
+1728522	581	596	clavulanic acid	Chemical	D019818
+1728522	CID	D019980	D056486
+1728522	CID	D019980	D006099
+1728522	CID	D019980	D002779
+
+10807237|t|Intracranial aneurysms and cocaine abuse: analysis of prognostic indicators.
+10807237|a|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.
+10807237	0	22	Intracranial aneurysms	Disease	D002532
+10807237	27	40	cocaine abuse	Disease	D019970
+10807237	103	126	subarachnoid hemorrhage	Disease	D013345
+10807237	143	156	cocaine abuse	Disease	D019970
+10807237	387	394	cocaine	Chemical	D003042
+10807237	403	412	aneurysms	Disease	D000783
+10807237	480	498	ruptured aneurysms	Disease	D017542
+10807237	517	530	cocaine abuse	Disease	D019970
+10807237	610	633	subarachnoid hemorrhage	Disease	D013345
+10807237	647	655	aneurysm	Disease	D000783
+10807237	673	681	aneurysm	Disease	D000783
+10807237	903	912	aneurysms	Disease	D000783
+10807237	977	986	aneurysms	Disease	D000783
+10807237	1281	1288	cocaine	Chemical	D003042
+10807237	1297	1306	aneurysms	Disease	D000783
+10807237	1320	1327	Cocaine	Chemical	D003042
+10807237	1344	1362	aneurysmal rupture	Disease	D017542
+10807237	1414	1423	aneurysms	Disease	D000783
+10807237	CID	D003042	D017542
+
+12536034|t|Anti-epileptic drugs-induced de novo absence seizures.
+12536034|a|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.
+12536034	5	14	epileptic	Disease	D004827
+12536034	37	53	absence seizures	Disease	D004832
+12536034	103	119	absence epilepsy	Disease	D004832
+12536034	144	157	carbamazepine	Chemical	D002220
+12536034	162	172	vigabatrin	Chemical	D020888
+12536034	246	261	absence seizure	Disease	D004832
+12536034	354	377	gamma-aminobutyric acid	Chemical	D005680
+12536034	483	499	absence epilepsy	Disease	D004832
+12536034	530	545	absence seizure	Disease	D004832
+12536034	752	767	absence seizure	Disease	D004832
+12536034	869	876	seizure	Disease	D012640
+12536034	898	905	seizure	Disease	D012640
+12536034	1002	1018	absence epilepsy	Disease	D004832
+12536034	1091	1099	epilepsy	Disease	D004827
+12536034	1125	1141	absence seizures	Disease	D004832
+12536034	CID	D020888	D004832
+12536034	CID	D002220	D004832
+
+7234705|t|Procainamide-induced polymorphous ventricular tachycardia.
+7234705|a|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.
+7234705	0	12	Procainamide	Chemical	D011342
+7234705	34	57	ventricular tachycardia	Disease	D017180
+7234705	74	86	procainamide	Chemical	D011342
+7234705	108	131	ventricular tachycardia	Disease	D017180
+7234705	178	201	ventricular tachycardia	Disease	D017180
+7234705	264	276	procainamide	Chemical	D011342
+7234705	308	331	ventricular tachycardia	Disease	D017180
+7234705	366	378	procainamide	Chemical	D011342
+7234705	428	462	premature ventricular contractions	Disease	D018879
+7234705	466	480	atrial flutter	Disease	D001282
+7234705	501	517	Q-T prolongation	Disease	D008133
+7234705	532	539	syncope	Disease	D013575
+7234705	560	583	ventricular tachycardia	Disease	D017180
+7234705	607	617	arrhythmia	Disease	D001145
+7234705	698	708	arrhythmia	Disease	D001145
+7234705	731	741	arrhythmia	Disease	D001145
+7234705	772	796	ventricular fibrillation	Disease	D014693
+7234705	921	933	procainamide	Chemical	D011342
+7234705	956	979	ventricular tachycardia	Disease	D017180
+7234705	1032	1044	procainamide	Chemical	D011342
+7234705	1069	1091	prolonged Q-T syndrome	Disease	D008133
+7234705	1110	1133	ventricular tachycardia	Disease	D017180
+7234705	CID	D011342	D017180
+
+8955532|t|Role of activation of bradykinin B2 receptors in disruption of the blood-brain barrier during acute hypertension.
+8955532|a|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.
+8955532	22	32	bradykinin	Chemical	D001920
+8955532	100	112	hypertension	Disease	D006973
+8955532	200	212	hypertension	Disease	D006973
+8955532	301	311	bradykinin	Chemical	D001920
+8955532	391	403	hypertension	Disease	D006973
+8955532	497	504	dextran	Chemical	D003911
+8955532	523	536	phenylephrine	Chemical	D010656
+8955532	551	563	hypertension	Disease	D006973
+8955532	597	604	Hoe-140	Chemical	C065679
+8955532	619	632	Phenylephrine	Chemical	D010656
+8955532	720	727	dextran	Chemical	D003911
+8955532	846	858	hypertension	Disease	D006973
+8955532	902	912	bradykinin	Chemical	D001920
+8955532	CID	D010656	D006973
+
+2578334|t|5-azacytidine potentiates initiation induced by carcinogens in rat liver.
+2578334|a|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.
+2578334	0	13	5-azacytidine	Chemical	D001374
+2578334	26	59	initiation induced by carcinogens	Disease	D011230
+2578334	172	206	initiation of carcinogenic process	Disease	D011230
+2578334	208	221	5-azacytidine	Chemical	D001374
+2578334	223	228	5-AzC	Chemical	D001374
+2578334	364	379	benzo[a]-pyrene	Chemical	D001564
+2578334	393	415	N-methyl-N-nitrosourea	Chemical	D008770
+2578334	431	452	1,2-dimethylhydrazine	Chemical	D019813
+2578334	454	461	1,2-DMH	Chemical	D019813
+2578334	658	679	2-acetylaminofluorene	Chemical	D015073
+2578334	714	718	CCl4	Chemical	D002251
+2578334	801	806	5-AzC	Chemical	D001374
+2578334	911	916	5-AzC	Chemical	D001374
+2578334	1028	1051	[3H]-5-azadeoxycytidine	Chemical	C014347
+2578334	1091	1098	1,2-DMH	Chemical	D019813
+2578334	1134	1142	cytosine	Chemical	D003596
+2578334	1226	1231	5-AzC	Chemical	D001374
+2578334	1298	1303	5-AzC	Chemical	D001374
+2578334	CID	D015073	D011230
+2578334	CID	D001564	D011230
+2578334	CID	D002251	D011230
+2578334	CID	D001374	D011230
+2578334	CID	D019813	D011230
+2578334	CID	D008770	D011230
+
+11532387|t|Withdrawal-emergent rabbit syndrome during dose reduction of risperidone.
+11532387|a|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.
+11532387	0	35	Withdrawal-emergent rabbit syndrome	Disease	D013375|D001480	Withdrawal syndrome|emergent rabbit syndrome
+11532387	61	72	risperidone	Chemical	D018967
+11532387	74	89	Rabbit syndrome	Disease	D001480
+11532387	91	93	RS	Disease	D001480
+11532387	202	224	withdrawal-emergent RS	Disease	D013375|D001480	withdrawal RS|emergent RS
+11532387	295	297	RS	Disease	D001480
+11532387	323	334	risperidone	Chemical	D018967
+11532387	378	393	trihexyphenidyl	Chemical	D014282
+11532387	447	469	withdrawal-emergent RS	Disease	D013375|D001480	withdrawal RS|emergent RS
+11532387	546	557	risperidone	Chemical	D018967
+11532387	561	570	serotonin	Chemical	D012701
+11532387	571	579	dopamine	Chemical	D004298
+11532387	641	650	serotonin	Chemical	D012701
+11532387	680	682	RS	Disease	D001480
+11532387	CID	D018967	D001480
+11532387	CID	D018967	D013375
+
+3173179|t|Verapamil withdrawal as a possible cause of myocardial infarction in a hypertensive woman with a normal coronary angiogram.
+3173179|a|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.
+3173179	0	9	Verapamil	Chemical	D014700
+3173179	44	65	myocardial infarction	Disease	D009203
+3173179	71	83	hypertensive	Disease	D006973
+3173179	124	133	Verapamil	Chemical	D014700
+3173179	266	276	depression	Disease	D003866
+3173179	408	429	myocardial infarction	Disease	D009203
+3173179	465	474	captopril	Chemical	D002216
+3173179	497	506	verapamil	Chemical	D014700
+3173179	554	566	hypertension	Disease	D006973
+3173179	603	612	verapamil	Chemical	D014700
+3173179	694	708	catecholamines	Chemical	D002395
+3173179	CID	D014700	D009203
+
+3856631|t|Remission induction of meningeal leukemia with high-dose intravenous methotrexate.
+3856631|a|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.
+3856631	23	41	meningeal leukemia	Disease	D008577
+3856631	69	81	methotrexate	Chemical	D008727
+3856631	104	132	acute lymphoblastic leukemia	Disease	D054198
+3856631	147	164	meningeal disease	Disease	D002493
+3856631	207	219	methotrexate	Chemical	D008727
+3856631	274	286	methotrexate	Chemical	D008727
+3856631	375	387	methotrexate	Chemical	D008727
+3856631	518	528	Leucovorin	Chemical	D002955
+3856631	717	729	methotrexate	Chemical	D008727
+3856631	814	826	methotrexate	Chemical	D008727
+3856631	1053	1063	toxicities	Disease	D064420
+3856631	1114	1123	bilirubin	Chemical	D001663
+3856631	1136	1147	neutropenia	Disease	D009503
+3856631	1153	1162	mucositis	Disease	D052016
+3856631	1186	1194	seizures	Disease	D012640
+3856631	1199	1220	transient hemiparesis	Disease	D010291
+3856631	1269	1281	methotrexate	Chemical	D008727
+3856631	1366	1394	acute lymphoblastic leukemia	Disease	D054198
+3856631	CID	D008727	D010291
+3856631	CID	D008727	D009503
+3856631	CID	D008727	D012640
+3856631	CID	D008727	D052016
+
+2522601|t|Hypersensitivity to carbamazepine presenting with a leukemoid reaction, eosinophilia, erythroderma, and renal failure.
+2522601|a|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.
+2522601	0	16	Hypersensitivity	Disease	D004342
+2522601	20	33	carbamazepine	Chemical	D002220
+2522601	52	70	leukemoid reaction	Disease	D007955
+2522601	72	84	eosinophilia	Disease	D004802
+2522601	86	98	erythroderma	Disease	D003873
+2522601	104	117	renal failure	Disease	D051437
+2522601	147	163	hypersensitivity	Disease	D004342
+2522601	167	180	carbamazepine	Chemical	D002220
+2522601	208	220	erythroderma	Disease	D003873
+2522601	231	249	leukemoid reaction	Disease	D007955
+2522601	251	263	eosinophilia	Disease	D004802
+2522601	265	277	hyponatremia	Disease	D007010
+2522601	283	296	renal failure	Disease	D051437
+2522601	354	367	carbamazepine	Chemical	D002220
+2522601	CID	D002220	D051437
+2522601	CID	D002220	D003873
+2522601	CID	D002220	D007955
+2522601	CID	D002220	D004342
+2522601	CID	D002220	D007010
+
+8741744|t|The interpeduncular nucleus regulates nicotine's effects on free-field activity.
+8741744|a|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.
+8741744	38	46	nicotine	Chemical	D009538
+8741744	112	123	kainic acid	Chemical	D007608
+8741744	301	323	locomotor hypoactivity	Disease	D009069
+8741744	334	342	nicotine	Chemical	D009538
+8741744	398	406	nicotine	Chemical	D009538
+8741744	415	428	hyperactivity	Disease	D006948
+8741744	535	542	choline	Chemical	D002794
+8741744	616	624	tyrosine	Chemical	D014443
+8741744	750	760	depression	Disease	D003866
+8741744	CID	D009538	D006948
+
+17491223|t|Assessment of a new non-invasive index of cardiac performance for detection of dobutamine-induced myocardial ischemia.
+17491223|a|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.
+17491223	79	89	dobutamine	Chemical	D004280
+17491223	98	117	myocardial ischemia	Disease	D017202
+17491223	191	201	dobutamine	Chemical	D004280
+17491223	210	229	myocardial ischemia	Disease	D017202
+17491223	429	439	dobutamine	Chemical	D004280
+17491223	448	467	myocardial ischemia	Disease	D017202
+17491223	475	490	Tc99m-Sestamibi	Chemical	D017256
+17491223	606	614	ischemia	Disease	D007511
+17491223	674	683	Sestamibi	Chemical	D017256
+17491223	690	700	dobutamine	Chemical	D004280
+17491223	799	809	dobutamine	Chemical	D004280
+17491223	876	884	ischemia	Disease	D007511
+17491223	953	963	dobutamine	Chemical	D004280
+17491223	1562	1581	myocardial ischemia	Disease	D017202
+17491223	CID	D004280	D017202
+
+18004067|t|Acute liver failure in two patients with regular alcohol consumption ingesting paracetamol at therapeutic dosage.
+18004067|a|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.
+18004067	0	19	Acute liver failure	Disease	D017114
+18004067	49	56	alcohol	Chemical	D000431
+18004067	79	90	paracetamol	Chemical	D000082
+18004067	147	154	alcohol	Chemical	D000431
+18004067	177	191	hepatotoxicity	Disease	D056486
+18004067	229	240	paracetamol	Chemical	D000082
+18004067	242	255	acetaminophen	Chemical	D000082
+18004067	345	352	alcohol	Chemical	D000431
+18004067	371	384	liver failure	Disease	D017093
+18004067	436	443	alcohol	Chemical	D000431
+18004067	485	496	paracetamol	Chemical	D000082
+18004067	504	515	paracetamol	Chemical	D000082
+18004067	635	649	hepatotoxicity	Disease	D056486
+18004067	696	707	paracetamol	Chemical	D000082
+18004067	794	801	alcohol	Chemical	D000431
+18004067	803	816	liver failure	Disease	D017093
+18004067	886	897	paracetamol	Chemical	D000082
+18004067	1029	1040	paracetamol	Chemical	D000082
+18004067	CID	D000082	D056486
+18004067	CID	D000082	D017093
+
+12443032|t|Cocaine related chest pain: are we seeing the tip of an iceberg?
+12443032|a|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.
+12443032	0	7	Cocaine	Chemical	D003042
+12443032	16	26	chest pain	Disease	D002637
+12443032	89	96	cocaine	Chemical	D003042
+12443032	206	213	cocaine	Chemical	D003042
+12443032	250	257	cocaine	Chemical	D003042
+12443032	269	279	chest pain	Disease	D002637
+12443032	361	371	chest pain	Disease	D002637
+12443032	419	429	chest pain	Disease	D002637
+12443032	441	448	cocaine	Chemical	D003042
+12443032	563	570	cocaine	Chemical	D003042
+12443032	CID	D003042	D002637
+
+17615423|t|Severe rhabdomyolysis and acute renal failure secondary to concomitant use of simvastatin, amiodarone, and atazanavir.
+17615423|a|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.
+17615423	7	21	rhabdomyolysis	Disease	D012206
+17615423	26	45	acute renal failure	Disease	D058186
+17615423	78	89	simvastatin	Chemical	D019821
+17615423	91	101	amiodarone	Chemical	D000638
+17615423	107	117	atazanavir	Chemical	C413408
+17615423	179	190	simvastatin	Chemical	D019821
+17615423	192	202	amiodarone	Chemical	D000638
+17615423	208	218	atazanavir	Chemical	C413408
+17615423	232	246	rhabdomyolysis	Disease	D012206
+17615423	251	270	acute renal failure	Disease	D058186
+17615423	324	352	human immunodeficiency virus	Disease	D015658
+17615423	354	373	atrial fibrillation	Disease	D001281
+17615423	375	398	coronary artery disease	Disease	D003324
+17615423	404	418	hyperlipidemia	Disease	D006949
+17615423	446	450	pain	Disease	D010146
+17615423	452	459	fatigue	Disease	D005221
+17615423	524	535	simvastatin	Chemical	D019821
+17615423	576	586	amiodarone	Chemical	D000638
+17615423	683	693	atazanavir	Chemical	C413408
+17615423	783	791	creatine	Chemical	D003401
+17615423	809	828	blood urea nitrogen	Chemical	D001806
+17615423	840	850	creatinine	Chemical	D003404
+17615423	861	870	aspartate	Chemical	D001224
+17615423	901	908	alanine	Chemical	D000409
+17615423	927	938	Simvastatin	Chemical	D019821
+17615423	940	950	amiodarone	Chemical	D000638
+17615423	970	998	human immunodeficiency virus	Disease	D015658
+17615423	1151	1159	creatine	Chemical	D003401
+17615423	1195	1205	creatinine	Chemical	D003404
+17615423	1354	1368	rhabdomyolysis	Disease	D012206
+17615423	1432	1443	simvastatin	Chemical	D019821
+17615423	1456	1467	Simvastatin	Chemical	D019821
+17615423	1494	1504	Amiodarone	Chemical	D000638
+17615423	1509	1519	atazanavir	Chemical	C413408
+17615423	1598	1605	statins	Chemical	D019821
+17615423	1736	1743	statins	Chemical	D019821
+17615423	1767	1778	pravastatin	Chemical	D017035
+17615423	1780	1791	fluvastatin	Chemical	C065180
+17615423	1797	1809	rosuvastatin	Chemical	C422923
+17615423	1854	1866	atorvastatin	Chemical	C065179
+17615423	1898	1909	simvastatin	Chemical	D019821
+17615423	1914	1924	lovastatin	Chemical	D008148
+17615423	CID	D000638	D058186
+17615423	CID	C413408	D058186
+17615423	CID	D019821	D012206
+17615423	CID	D019821	D058186
+17615423	CID	D000638	D012206
+17615423	CID	C413408	D012206
+
+8558192|t|Phase II trial of vinorelbine in metastatic squamous cell esophageal carcinoma. European Organization for Research and Treatment of Cancer Gastrointestinal Treat Cancer Cooperative Group.
+8558192|a|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.
+8558192	18	29	vinorelbine	Chemical	C030852
+8558192	44	78	squamous cell esophageal carcinoma	Disease	C562729
+8558192	132	138	Cancer	Disease	D009369
+8558192	162	168	Cancer	Disease	D009369
+8558192	248	259	vinorelbine	Chemical	C030852
+8558192	261	264	VNB	Chemical	C030852
+8558192	311	345	squamous cell esophageal carcinoma	Disease	C562729
+8558192	557	566	cisplatin	Chemical	D002945
+8558192	606	614	toxicity	Disease	D064420
+8558192	629	632	VNB	Chemical	C030852
+8558192	1189	1192	VNB	Chemical	C030852
+8558192	1261	1269	toxicity	Disease	D064420
+8558192	1317	1333	granulocytopenia	Disease	D000380
+8558192	1378	1387	infection	Disease	D007239
+8558192	1430	1436	deaths	Disease	D003643
+8558192	1481	1505	peripheral neurotoxicity	Disease	D010523
+8558192	1573	1576	VNB	Chemical	C030852
+8558192	1610	1644	esophageal squamous cell carcinoma	Disease	C562729
+8558192	1692	1700	toxicity	Disease	D064420
+8558192	1724	1727	VNB	Chemical	C030852
+8558192	CID	C030852	D000380
+8558192	CID	C030852	D010523
+
+11135224|t|Paclitaxel, cisplatin, and gemcitabine combination chemotherapy within a multidisciplinary therapeutic approach in metastatic nonsmall cell lung carcinoma.
+11135224|a|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.
+11135224	0	10	Paclitaxel	Chemical	D017239
+11135224	12	21	cisplatin	Chemical	D002945
+11135224	27	38	gemcitabine	Chemical	C056507
+11135224	126	154	nonsmall cell lung carcinoma	Disease	D002289
+11135224	168	177	Cisplatin	Chemical	D002945
+11135224	259	287	nonsmall cell lung carcinoma	Disease	D002289
+11135224	289	294	NSCLC	Disease	D002289
+11135224	501	509	toxicity	Disease	D064420
+11135224	515	525	paclitaxel	Chemical	D017239
+11135224	527	536	cisplatin	Chemical	D002945
+11135224	542	553	gemcitabine	Chemical	C056507
+11135224	586	591	NSCLC	Disease	D002289
+11135224	659	664	NSCLC	Disease	D002289
+11135224	768	778	paclitaxel	Chemical	D017239
+11135224	834	843	cisplatin	Chemical	D002945
+11135224	903	914	gemcitabine	Chemical	C056507
+11135224	1182	1190	toxicity	Disease	D064420
+11135224	1296	1304	toxicity	Disease	D064420
+11135224	1651	1661	paclitaxel	Chemical	D017239
+11135224	1687	1696	cisplatin	Chemical	D002945
+11135224	1727	1738	gemcitabine	Chemical	C056507
+11135224	1784	1795	neutropenia	Disease	D009503
+11135224	1800	1816	thrombocytopenia	Disease	D013921
+11135224	1904	1909	death	Disease	D003643
+11135224	1926	1936	toxicities	Disease	D064420
+11135224	2119	2129	paclitaxel	Chemical	D017239
+11135224	2131	2140	cisplatin	Chemical	D002945
+11135224	2146	2157	gemcitabine	Chemical	C056507
+11135224	2214	2219	NSCLC	Disease	D002289
+11135224	2273	2282	cisplatin	Chemical	D002945
+11135224	CID	D002945	D009503
+11135224	CID	D017239	D013921
+11135224	CID	C056507	D009503
+11135224	CID	D017239	D009503
+11135224	CID	C056507	D013921
+11135224	CID	D002945	D013921
+
+8590259|t|Evaluation of adverse reactions of aponidine hydrochloride ophthalmic solution.
+8590259|a|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.
+8590259	35	58	aponidine hydrochloride	Chemical	C016986
+8590259	132	145	apraclonidine	Chemical	C016986
+8590259	204	217	apraclonidine	Chemical	C016986
+8590259	521	539	ocular hypotensive	Disease	D015814
+8590259	583	596	apraclonidine	Chemical	C016986
+8590259	741	754	apraclonidine	Chemical	C016986
+8590259	756	792	Decreases in systolic blood pressure	Disease	D007022
+8590259	946	968	Conjunctival blanching	Disease	D003229
+8590259	973	982	mydriasis	Disease	D015878
+8590259	1221	1230	entropion	Disease	D004774
+8590259	1242	1258	corneal abrasion	Disease	D003316
+8590259	CID	C016986	D015814
+8590259	CID	C016986	D015878
+8590259	CID	C016986	D004774
+8590259	CID	C016986	D003316
+8590259	CID	C016986	D003229
+
+2096243|t|Carmofur-induced organic mental disorders.
+2096243|a|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.
+2096243	0	8	Carmofur	Chemical	C017367
+2096243	17	41	organic mental disorders	Disease	D019965
+2096243	43	66	Organic mental disorder	Disease	D019965
+2096243	148	156	carmofur	Chemical	C017367
+2096243	165	184	leukoencephalopathy	Disease	D056784
+2096243	292	320	organic personality syndrome	Disease	D010554
+2096243	396	417	frontal lobe syndrome	Disease	D001927
+2096243	608	616	carmofur	Chemical	C017367
+2096243	625	644	leukoencephalopathy	Disease	D056784
+2096243	670	698	organic personality syndrome	Disease	D010554
+2096243	750	787	structural damage to the frontal lobe	Disease	D001927
+2096243	CID	C017367	D056784
+2096243	CID	C017367	D019965
+
+6209318|t|International mexiletine and placebo antiarrhythmic coronary trial: I. Report on arrhythmia and other findings. Impact Research Group.
+6209318|a|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.
+6209318	14	24	mexiletine	Chemical	D008801
+6209318	81	91	arrhythmia	Disease	D001145
+6209318	195	205	mexiletine	Chemical	D008801
+6209318	207	225	Mexitil-Perlongets	Chemical	D008801
+6209318	313	334	myocardial infarction	Disease	D009203
+6209318	767	777	mexiletine	Chemical	D008801
+6209318	942	952	mexiletine	Chemical	D008801
+6209318	1096	1102	deaths	Disease	D003643
+6209318	1110	1120	mexiletine	Chemical	D008801
+6209318	1328	1334	tremor	Disease	D014202
+6209318	1339	1364	gastrointestinal problems	Disease	D012817
+6209318	1392	1402	mexiletine	Chemical	D008801
+6209318	CID	D008801	D014202
+6209318	CID	D008801	D012817
+
+3615541|t|Regional localization of the antagonism of amphetamine-induced hyperactivity by intracerebral calcitonin injections.
+3615541|a|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.
+3615541	43	54	amphetamine	Chemical	D000661
+3615541	63	76	hyperactivity	Disease	D006948
+3615541	94	104	calcitonin	Chemical	D002116
+3615541	117	127	Calcitonin	Chemical	D002116
+3615541	193	203	calcitonin	Chemical	D002116
+3615541	313	324	amphetamine	Chemical	D000661
+3615541	456	466	calcitonin	Chemical	D002116
+3615541	557	567	calcitonin	Chemical	D002116
+3615541	687	697	calcitonin	Chemical	D002116
+3615541	865	875	calcitonin	Chemical	D002116
+3615541	890	901	amphetamine	Chemical	D000661
+3615541	CID	D000661	D006948
+
+8953972|t|Fatal intracranial bleeding associated with prehospital use of epinephrine.
+8953972|a|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.
+8953972	6	27	intracranial bleeding	Disease	D013345
+8953972	63	74	epinephrine	Chemical	D004837
+8953972	171	188	allergic reaction	Disease	D004342
+8953972	202	217	pulmonary edema	Disease	D011654
+8953972	223	231	wheezing	Disease	D012135
+8953972	253	273	respiratory distress	Disease	D012128
+8953972	275	279	rash	Disease	D005076
+8953972	376	387	epinephrine	Chemical	D004837
+8953972	409	423	cardiac arrest	Disease	D006323
+8953972	434	457	subarachnoid hemorrhage	Disease	D013345
+8953972	468	479	Epinephrine	Chemical	D004837
+8953972	501	515	cardiac arrest	Disease	D006323
+8953972	591	608	allergic reaction	Disease	D004342
+8953972	620	632	hypertension	Disease	D006973
+8953972	CID	D004837	D013345
+8953972	CID	D004837	D006323
+
+3782049|t|A case of massive rhabdomyolysis following molindone administration.
+3782049|a|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.
+3782049	18	32	rhabdomyolysis	Disease	D012206
+3782049	43	52	molindone	Chemical	D008972
+3782049	69	83	Rhabdomyolysis	Disease	D012206
+3782049	122	133	psychiatric	Disease	D001523
+3782049	255	269	rhabdomyolysis	Disease	D012206
+3782049	299	312	schizophrenic	Disease	D012559
+3782049	355	369	rhabdomyolysis	Disease	D012206
+3782049	385	404	acute renal failure	Disease	D058186
+3782049	415	424	molindone	Chemical	D008972
+3782049	466	475	molindone	Chemical	D008972
+3782049	CID	D008972	D012206
+3782049	CID	D008972	D058186
+
+9100294|t|Cardiovascular alterations in rat fetuses exposed to calcium channel blockers.
+9100294|a|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.
+9100294	0	26	Cardiovascular alterations	Disease	D018376
+9100294	53	60	calcium	Chemical	D002118
+9100294	138	145	calcium	Chemical	D002118
+9100294	163	173	Ro 40-5967	Chemical	D020748
+9100294	183	209	cardiovascular alterations	Disease	D018376
+9100294	335	342	calcium	Chemical	D002118
+9100294	378	406	cardiovascular malformations	Disease	D018376
+9100294	465	472	calcium	Chemical	D002118
+9100294	514	524	nifedipine	Chemical	D009543
+9100294	526	535	diltiazem	Chemical	D004110
+9100294	541	550	verapamil	Chemical	D014700
+9100294	623	630	calcium	Chemical	D002118
+9100294	745	773	cardiovascular malformations	Disease	D018376
+9100294	794	822	cardiovascular malformations	Disease	D018376
+9100294	871	878	calcium	Chemical	D002118
+9100294	955	964	verapamil	Chemical	D014700
+9100294	969	979	nifedipine	Chemical	D009543
+9100294	1092	1102	Ro 40-5967	Chemical	D020748
+9100294	1107	1116	verapamil	Chemical	D014700
+9100294	CID	D014700	D018376
+9100294	CID	D009543	D018376
+9100294	CID	D020748	D018376
+
+19889778|t|Differential impact of immune escape mutations G145R and P120T on the replication of lamivudine-resistant hepatitis B virus e antigen-positive and -negative strains.
+19889778|a|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.
+19889778	85	95	lamivudine	Chemical	D019259
+19889778	106	133	hepatitis B virus e antigen	Chemical	D006513
+19889778	196	207	hepatitis B	Disease	D006509
+19889778	774	784	lamivudine	Chemical	D019259
+19889778	786	789	LAM	Chemical	D019259
+19889778	798	803	HBeAg	Chemical	D006513
+19889778	876	879	LAM	Chemical	D019259
+19889778	941	946	HBeAg	Chemical	D006513
+19889778	963	968	HBeAg	Chemical	D006513
+19889778	1083	1088	HBsAg	Chemical	D006514
+19889778	1154	1157	LAM	Chemical	D019259
+19889778	1319	1324	HBsAg	Chemical	D006514
+19889778	1374	1377	LAM	Chemical	D019259
+19889778	1435	1440	HBeAg	Chemical	D006513
+19889778	1474	1477	LAM	Chemical	D019259
+19889778	1606	1609	LAM	Chemical	D019259
+19889778	1636	1646	nucleotide	Chemical	D009711
+19889778	1657	1665	adefovir	Chemical	C053001
+19889778	1670	1679	tenofovir	Chemical	C096918
+19889778	CID	D006514	D006509
+19889778	CID	D006513	D006509
+
+15278670|t|The effects of sevoflurane on lidocaine-induced convulsions.
+15278670|a|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.
+15278670	15	26	sevoflurane	Chemical	C009250
+15278670	30	39	lidocaine	Chemical	D008012
+15278670	48	59	convulsions	Disease	D012640
+15278670	78	89	sevoflurane	Chemical	C009250
+15278670	93	102	lidocaine	Chemical	D008012
+15278670	111	122	convulsions	Disease	D012640
+15278670	148	158	convulsive	Disease	D012640
+15278670	215	224	lidocaine	Chemical	D008012
+15278670	345	356	sevoflurane	Chemical	C009250
+15278670	427	438	sevoflurane	Chemical	C009250
+15278670	481	492	sevoflurane	Chemical	C009250
+15278670	566	576	convulsive	Disease	D012640
+15278670	595	606	sevoflurane	Chemical	C009250
+15278670	611	620	enflurane	Chemical	D004737
+15278670	698	709	sevoflurane	Chemical	C009250
+15278670	713	722	enflurane	Chemical	D004737
+15278670	767	778	convulsions	Disease	D012640
+15278670	811	822	sevoflurane	Chemical	C009250
+15278670	845	854	enflurane	Chemical	D004737
+15278670	908	917	lidocaine	Chemical	D008012
+15278670	991	997	Apamin	Chemical	D001030
+15278670	1022	1029	calcium	Chemical	D002118
+15278670	1040	1049	potassium	Chemical	D011188
+15278670	1134	1145	sevoflurane	Chemical	C009250
+15278670	1206	1212	Apamin	Chemical	D001030
+15278670	1252	1262	convulsive	Disease	D012640
+15278670	1379	1390	sevoflurane	Chemical	C009250
+15278670	1403	1413	convulsive	Disease	D012640
+15278670	1424	1433	lidocaine	Chemical	D008012
+15278670	1434	1442	toxicity	Disease	D064420
+15278670	1484	1494	depression	Disease	D003866
+15278670	CID	D008012	D012640
+
+17042910|t|Anti-oxidant effects of atorvastatin in dexamethasone-induced hypertension in the rat.
+17042910|a|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.
+17042910	24	36	atorvastatin	Chemical	C065179
+17042910	40	53	dexamethasone	Chemical	D003907
+17042910	62	74	hypertension	Disease	D006973
+17042910	90	103	Dexamethasone	Chemical	D003907
+17042910	105	108	Dex	Chemical	D003907
+17042910	118	130	hypertension	Disease	D006973
+17042910	191	203	nitric oxide	Chemical	D009569
+17042910	205	207	NO	Chemical	D009569
+17042910	234	244	superoxide	Chemical	D013481
+17042910	246	249	O2-	Chemical	D013481
+17042910	263	275	Atorvastatin	Chemical	C065179
+17042910	277	280	Ato	Chemical	C065179
+17042910	405	407	NO	Chemical	D009569
+17042910	420	423	O2-	Chemical	D013481
+17042910	455	467	hypertension	Disease	D006973
+17042910	539	542	Ato	Chemical	C065179
+17042910	569	571	NO	Chemical	D009569
+17042910	623	626	O2-	Chemical	D013481
+17042910	732	735	Ato	Chemical	C065179
+17042910	799	812	Dexamethasone	Chemical	D003907
+17042910	880	883	Ato	Chemical	C065179
+17042910	1069	1082	acetylcholine	Chemical	D000109
+17042910	1110	1123	phenylephrine	Chemical	D010656
+17042910	1295	1298	Dex	Chemical	D003907
+17042910	1412	1415	Ato	Chemical	C065179
+17042910	1418	1421	Dex	Chemical	D003907
+17042910	1586	1589	Dex	Chemical	D003907
+17042910	1686	1689	Dex	Chemical	D003907
+17042910	1692	1695	Ato	Chemical	C065179
+17042910	1714	1717	Dex	Chemical	D003907
+17042910	1777	1787	superoxide	Chemical	D013481
+17042910	1816	1819	Dex	Chemical	D003907
+17042910	1822	1825	Ato	Chemical	C065179
+17042910	1869	1872	Dex	Chemical	D003907
+17042910	1911	1914	Ato	Chemical	C065179
+17042910	1954	1964	superoxide	Chemical	D013481
+17042910	1995	1998	Dex	Chemical	D003907
+17042910	CID	D003907	D006973
+
+11897407|t|99mTc-glucarate for detection of isoproterenol-induced myocardial infarction in rats.
+11897407|a|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.
+11897407	0	15	99mTc-glucarate	Chemical	C067171
+11897407	33	46	isoproterenol	Chemical	D007545
+11897407	55	76	myocardial infarction	Disease	D009203
+11897407	86	93	Infarct	Disease	D007238
+11897407	174	195	myocardial infarction	Disease	D009203
+11897407	230	240	infarction	Disease	D007238
+11897407	316	329	isoproterenol	Chemical	D007545
+11897407	337	344	infarct	Disease	D007238
+11897407	379	392	glucaric acid	Chemical	D005937
+11897407	452	467	99mTc-glucarate	Chemical	C067171
+11897407	560	573	isoproterenol	Chemical	D007545
+11897407	588	609	myocardial infarction	Disease	D009203
+11897407	672	679	infarct	Disease	D007238
+11897407	691	704	isoproterenol	Chemical	D007545
+11897407	822	837	99mTc-glucarate	Chemical	C067171
+11897407	1196	1214	cardiac infarction	Disease	D009203
+11897407	CID	D007545	D009203
+
+9812111|t|A randomized, placebo-controlled dose-comparison trial of haloperidol for psychosis and disruptive behaviors in Alzheimer's disease.
+9812111|a|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.
+9812111	58	69	haloperidol	Chemical	D006220
+9812111	74	83	psychosis	Disease	D011618
+9812111	88	108	disruptive behaviors	Disease	D019958
+9812111	112	131	Alzheimer's disease	Disease	D000544
+9812111	228	239	haloperidol	Chemical	D006220
+9812111	272	281	psychosis	Disease	D011618
+9812111	286	306	disruptive behaviors	Disease	D019958
+9812111	324	343	Alzheimer's disease	Disease	D000544
+9812111	434	445	haloperidol	Chemical	D006220
+9812111	479	490	haloperidol	Chemical	D006220
+9812111	558	577	Alzheimer's disease	Disease	D000544
+9812111	683	694	haloperidol	Chemical	D006220
+9812111	797	808	haloperidol	Chemical	D006220
+9812111	876	887	haloperidol	Chemical	D006220
+9812111	934	945	haloperidol	Chemical	D006220
+9812111	1007	1016	psychosis	Disease	D011618
+9812111	1031	1052	psychomotor agitation	Disease	D011595
+9812111	1286	1306	extrapyramidal signs	Disease	D001480
+9812111	1472	1483	haloperidol	Chemical	D006220
+9812111	1627	1638	haloperidol	Chemical	D006220
+9812111	1712	1732	extrapyramidal signs	Disease	D001480
+9812111	1858	1869	haloperidol	Chemical	D006220
+9812111	1915	1934	Alzheimer's disease	Disease	D000544
+9812111	1949	1958	psychosis	Disease	D011618
+9812111	1963	1983	disruptive behaviors	Disease	D019958
+9812111	CID	D006220	D001480
+
+15572383|t|Individual differences in renal ACE activity in healthy rats predict susceptibility to adriamycin-induced renal damage.
+15572383|a|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.
+15572383	87	97	adriamycin	Chemical	D004317
+15572383	106	118	renal damage	Disease	D007674
+15572383	155	166	angiotensin	Chemical	D000809
+15572383	488	500	renal damage	Disease	D007674
+15572383	534	544	adriamycin	Chemical	D004317
+15572383	583	594	Hip-His-Leu	Chemical	C010980
+15572383	716	727	proteinuria	Disease	D011507
+15572383	743	753	adriamycin	Chemical	D004317
+15572383	824	835	Proteinuria	Disease	D011507
+15572383	955	965	adriamycin	Chemical	D004317
+15572383	975	984	nephrotic	Disease	D009404
+15572383	991	1002	proteinuria	Disease	D011507
+15572383	1004	1029	renal interstitial damage	Disease	D007674
+15572383	1039	1063	focal glomerulosclerosis	Disease	D005923
+15572383	1132	1143	proteinuria	Disease	D011507
+15572383	1150	1160	adriamycin	Chemical	D004317
+15572383	1483	1507	focal glomerulosclerosis	Disease	D005923
+15572383	1675	1685	adriamycin	Chemical	D004317
+15572383	1694	1706	renal damage	Disease	D007674
+15572383	1845	1857	renal damage	Disease	D007674
+15572383	CID	D004317	D011507
+
+7420681|t|Clinical nephrotoxicity of tobramycin and gentamicin. A prospective study.
+7420681|a|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.
+7420681	9	23	nephrotoxicity	Disease	D007674
+7420681	27	37	tobramycin	Chemical	D014031
+7420681	42	52	gentamicin	Chemical	D005839
+7420681	125	139	aminoglycoside	Chemical	D000617
+7420681	162	180	Gentamicin sulfate	Chemical	D005839
+7420681	185	203	tobramycin sulfate	Chemical	D014031
+7420681	228	239	ototoxicity	Disease	D006311
+7420681	244	258	nephrotoxicity	Disease	D007674
+7420681	405	423	gentamicin sulfate	Chemical	D005839
+7420681	427	445	tobramycin sulfate	Chemical	D014031
+7420681	528	542	aminoglycoside	Chemical	D000617
+7420681	551	564	renal failure	Disease	D051437
+7420681	669	682	renal failure	Disease	D051437
+7420681	728	738	tobramycin	Chemical	D014031
+7420681	784	794	gentamicin	Chemical	D005839
+7420681	816	829	renal failure	Disease	D051437
+7420681	837	847	gentamicin	Chemical	D005839
+7420681	868	881	renal failure	Disease	D051437
+7420681	920	930	tobramycin	Chemical	D014031
+7420681	CID	D005839	D051437
+7420681	CID	D014031	D051437
+
+12907309|t|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.
+12907309|a|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.
+12907309	26	30	MPEP	Chemical	C121465
+12907309	66	81	methamphetamine	Chemical	D008694
+12907309	103	116	neurotoxicity	Disease	D020258
+12907309	150	158	dopamine	Chemical	D004298
+12907309	185	197	hyperthermia	Disease	D005334
+12907309	269	278	glutamate	Chemical	D018698
+12907309	322	337	methamphetamine	Chemical	D008694
+12907309	372	387	Methamphetamine	Chemical	D008694
+12907309	450	458	dopamine	Chemical	D004298
+12907309	577	611	2-methyl-6-(phenylethynyl)pyridine	Chemical	C121465
+12907309	613	617	MPEP	Chemical	C121465
+12907309	685	700	methamphetamine	Chemical	D008694
+12907309	740	755	methamphetamine	Chemical	D008694
+12907309	774	778	MPEP	Chemical	C121465
+12907309	834	842	dopamine	Chemical	D004298
+12907309	877	885	dopamine	Chemical	D004298
+12907309	915	930	methamphetamine	Chemical	D008694
+12907309	980	991	veratridine	Chemical	D014701
+12907309	1046	1061	methamphetamine	Chemical	D008694
+12907309	1084	1096	hyperthermia	Disease	D005334
+12907309	1133	1137	MPEP	Chemical	C121465
+12907309	1229	1237	dopamine	Chemical	D004298
+12907309	1381	1385	MPEP	Chemical	C121465
+12907309	1428	1443	methamphetamine	Chemical	D008694
+12907309	1452	1460	toxicity	Disease	D064420
+12907309	1490	1494	MPEP	Chemical	C121465
+12907309	1539	1554	methamphetamine	Chemical	D008694
+12907309	1563	1571	dopamine	Chemical	D004298
+12907309	1663	1675	hyperthermia	Disease	D005334
+12907309	CID	D008694	D005334
+
+16680561|t|Pharmacokinetics of desipramine HCl when administered with cinacalcet HCl.
+16680561|a|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.
+16680561	20	35	desipramine HCl	Chemical	D003891
+16680561	59	73	cinacalcet HCl	Chemical	C476217
+16680561	122	132	cinacalcet	Chemical	C476217
+16680561	251	261	cinacalcet	Chemical	C476217
+16680561	288	299	desipramine	Chemical	D003891
+16680561	518	529	desipramine	Chemical	D003891
+16680561	609	619	cinacalcet	Chemical	C476217
+16680561	771	782	desipramine	Chemical	D003891
+16680561	813	824	desipramine	Chemical	D003891
+16680561	878	888	cinacalcet	Chemical	C476217
+16680561	907	918	desipramine	Chemical	D003891
+16680561	935	946	desipramine	Chemical	D003891
+16680561	971	981	cinacalcet	Chemical	C476217
+16680561	1115	1126	desipramine	Chemical	D003891
+16680561	1153	1164	desipramine	Chemical	D003891
+16680561	1170	1180	cinacalcet	Chemical	C476217
+16680561	1226	1232	nausea	Disease	D009325
+16680561	1237	1245	headache	Disease	D006261
+16680561	1299	1310	desipramine	Chemical	D003891
+16680561	1314	1324	cinacalcet	Chemical	C476217
+16680561	1367	1377	cinacalcet	Chemical	C476217
+16680561	1469	1479	cinacalcet	Chemical	C476217
+16680561	CID	D003891	D009325
+16680561	CID	C476217	D006261
+16680561	CID	D003891	D006261
+16680561	CID	C476217	D009325
+
+17532790|t|Proteomic analysis of striatal proteins in the rat model of L-DOPA-induced dyskinesia.
+17532790|a|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.
+17532790	60	66	L-DOPA	Chemical	D007980
+17532790	75	85	dyskinesia	Disease	D004409
+17532790	87	93	L-DOPA	Chemical	D007980
+17532790	102	112	dyskinesia	Disease	D004409
+17532790	114	117	LID	Disease	D004409
+17532790	166	185	Parkinson's disease	Disease	D010300
+17532790	187	189	PD	Disease	D010300
+17532790	233	239	L-DOPA	Chemical	D007980
+17532790	314	317	LID	Disease	D004409
+17532790	541	558	6-hydroxydopamine	Chemical	D016627
+17532790	579	581	PD	Disease	D010300
+17532790	603	609	L-DOPA	Chemical	D007980
+17532790	613	626	bromocriptine	Chemical	D001971
+17532790	726	732	L-DOPA	Chemical	D007980
+17532790	798	801	LID	Disease	D004409
+17532790	1124	1127	LID	Disease	D004409
+17532790	1562	1565	LID	Disease	D004409
+17532790	CID	D007980	D004409
+
+7582165|t|Pseudo-allergic reactions to corticosteroids: diagnosis and alternatives.
+7582165|a|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.
+7582165	7	25	allergic reactions	Disease	D004342
+7582165	29	44	corticosteroids	Chemical	D000305
+7582165	111	124	paramethasone	Chemical	D010248
+7582165	139	152	dexamethasone	Chemical	D003907
+7582165	244	253	urticaria	Disease	D014581
+7582165	277	291	conjunctivitis	Disease	D003231
+7582165	577	592	corticosteroids	Chemical	D000305
+7582165	672	685	paramethasone	Chemical	D010248
+7582165	973	988	corticosteroids	Chemical	D000305
+7582165	1055	1068	paramethasone	Chemical	D010248
+7582165	1149	1162	paramethasone	Chemical	D010248
+7582165	1177	1193	hypersensitivity	Disease	D004342
+7582165	1387	1394	allergy	Disease	D004342
+7582165	1405	1418	paramethasone	Chemical	D010248
+7582165	CID	D010248	D014581
+7582165	CID	D003907	D003231
+7582165	CID	D003907	D014581
+7582165	CID	D010248	D003231
+
+16787750|t|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.
+16787750|a|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.
+16787750	0	13	Valproic acid	Chemical	D014635
+16787750	22	36	encephalopathy	Disease	D001927
+16787750	109	112	VPA	Chemical	D014635
+16787750	149	162	Valproic acid	Chemical	D014635
+16787750	164	167	VPA	Chemical	D014635
+16787750	317	329	pancreatitis	Disease	D010195
+16787750	331	354	bone marrow suppression	Disease	D001855
+16787750	356	359	VPA	Chemical	D014635
+16787750	368	382	hepatotoxicity	Disease	D056486
+16787750	387	390	VPA	Chemical	D014635
+16787750	399	413	encephalopathy	Disease	D001927
+16787750	436	439	VPA	Chemical	D014635
+16787750	448	462	encephalopathy	Disease	D001927
+16787750	467	489	impaired consciousness	Disease	D003244
+16787750	542	549	seizure	Disease	D012640
+16787750	577	591	hyperammonemia	Disease	D022124
+16787750	640	643	VPA	Chemical	D014635
+16787750	661	675	encephalopathy	Disease	D001927
+16787750	764	767	VPA	Chemical	D014635
+16787750	779	793	encephalopathy	Disease	D001927
+16787750	CID	D014635	D001855
+16787750	CID	D014635	D010195
+16787750	CID	D014635	D001927
+16787750	CID	D014635	D056486
+16787750	CID	D014635	D003244
+
+3173180|t|Haemolytic-uraemic syndrome after treatment with metronidazole.
+3173180|a|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.
+3173180	0	27	Haemolytic-uraemic syndrome	Disease	D006463
+3173180	49	62	metronidazole	Chemical	D008795
+3173180	141	168	haemolytic-uraemic syndrome	Disease	D006463
+3173180	190	203	metronidazole	Chemical	D008795
+3173180	361	374	metronidazole	Chemical	D008795
+3173180	399	426	haemolytic-uraemic syndrome	Disease	D006463
+3173180	575	602	haemolytic-uraemic syndrome	Disease	D006463
+3173180	635	648	metronidazole	Chemical	D008795
+3173180	681	708	haemolytic-uraemic syndrome	Disease	D006463
+3173180	CID	D008795	D006463
+
+8996652|t|Risk factors of sensorineural hearing loss in preterm infants.
+8996652|a|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.
+8996652	16	42	sensorineural hearing loss	Disease	D006319
+8996652	208	234	sensorineural hearing loss	Disease	D006319
+8996652	275	287	hearing loss	Disease	D034381
+8996652	455	467	hearing loss	Disease	D034381
+8996652	520	531	Ototoxicity	Disease	D006311
+8996652	612	620	ototoxic	Disease	D006311
+8996652	641	656	aminoglycosides	Chemical	D000617
+8996652	661	671	furosemide	Chemical	D005665
+8996652	793	805	hearing loss	Disease	D034381
+8996652	CID	D000617	D006319
+8996652	CID	D005665	D006319
+
+84204|t|Pharmacokinetic and clinical studies in patients with cimetidine-associated mental confusion.
+84204|a|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.
+84204	54	64	cimetidine	Chemical	D002927
+84204	83	92	confusion	Disease	D003221
+84204	106	116	cimetidine	Chemical	D002927
+84204	135	144	confusion	Disease	D003221
+84204	370	380	cimetidine	Chemical	D002927
+84204	445	472	renal and liver dysfunction	Disease	D051437|D008107	renal dysfunction|liver dysfunction
+84204	504	514	cimetidine	Chemical	D002927
+84204	730	740	cimetidine	Chemical	D002927
+84204	786	796	cimetidine	Chemical	D002927
+84204	901	910	histamine	Chemical	D006632
+84204	1024	1033	confusion	Disease	D003221
+84204	1061	1090	renal and hepatic dysfunction	Disease	D051437|D008107	renal dysfunction|hepatic dysfunction
+84204	1161	1171	cimetidine	Chemical	D002927
+84204	CID	D002927	D003221
+
+9862868|t|Different lobular distributions of altered hepatocyte tight junctions in rat models of intrahepatic and extrahepatic cholestasis.
+9862868|a|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.
+9862868	87	128	intrahepatic and extrahepatic cholestasis	Disease	D002780|D001651	intrahepatic cholestasis|extrahepatic cholestasis
+9862868	321	332	cholestasis	Disease	D002779
+9862868	678	702	intrahepatic cholestasis	Disease	D002780
+9862868	706	723	ethinyl estradiol	Chemical	D004997
+9862868	725	727	EE	Chemical	D004997
+9862868	743	767	extrahepatic cholestasis	Disease	D001651
+9862868	1356	1358	EE	Chemical	D004997
+9862868	1682	1684	EE	Chemical	D004997
+9862868	CID	D004997	D002780
+
+15515654|t|Long term audiological evaluation of beta-thalassemic patients.
+15515654|a|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.
+15515654	37	53	beta-thalassemic	Disease	D017086
+15515654	167	179	hearing loss	Disease	D034381
+15515654	214	230	beta-thalassemia	Disease	D017086
+15515654	479	494	desferrioxamine	Chemical	D003676
+15515654	496	499	DFO	Chemical	D003676
+15515654	804	830	sensorineural hearing loss	Disease	D006319
+15515654	832	836	SNHL	Disease	D006319
+15515654	874	882	ototoxic	Disease	D006311
+15515654	902	905	DFO	Chemical	D003676
+15515654	957	961	SNHL	Disease	D006319
+15515654	1125	1129	SNHL	Disease	D006319
+15515654	1148	1151	DFO	Chemical	D003676
+15515654	1346	1349	DFO	Chemical	D003676
+15515654	1392	1410	hearing impairment	Disease	D034381
+15515654	1463	1474	thalassemic	Disease	D013789
+15515654	1597	1615	hearing impairment	Disease	D034381
+15515654	CID	D003676	D006319
+
+2024540|t|Design and analysis of the HYPREN-trial: safety of enalapril and prazosin in the initial treatment phase of patients with congestive heart failure.
+2024540|a|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.
+2024540	51	60	enalapril	Chemical	D004656
+2024540	65	73	prazosin	Chemical	D011224
+2024540	122	146	congestive heart failure	Disease	D006333
+2024540	174	220	angiotensin converting enzyme (ACE) inhibitors	Chemical	D000806
+2024540	268	292	congestive heart failure	Disease	D006333
+2024540	310	321	hypotension	Disease	D007022
+2024540	426	439	ACE inhibitor	Chemical	D000806
+2024540	440	449	enalapril	Chemical	D004656
+2024540	477	485	prazosin	Chemical	D011224
+2024540	572	583	hypotension	Disease	D007022
+2024540	643	652	enalapril	Chemical	D004656
+2024540	660	668	prazosin	Chemical	D011224
+2024540	790	799	enalapril	Chemical	D004656
+2024540	872	883	hypotension	Disease	D007022
+2024540	922	930	prazosin	Chemical	D011224
+2024540	1001	1010	enalapril	Chemical	D004656
+2024540	1110	1119	enalapril	Chemical	D004656
+2024540	CID	D000806	D007022
+2024540	CID	D011224	D007022
+
+12090760|t|Antagonism between interleukin 3 and erythropoietin in mice with azidothymidine-induced anemia and in bone marrow endothelial cells.
+12090760|a|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.
+12090760	65	79	azidothymidine	Chemical	D015215
+12090760	88	94	anemia	Disease	D000740
+12090760	133	147	Azidothymidine	Chemical	D015215
+12090760	149	152	AZT	Chemical	D015215
+12090760	162	168	anemia	Disease	D000740
+12090760	472	475	AZT	Chemical	D015215
+12090760	924	933	thymidine	Chemical	D013936
+12090760	1187	1196	thymidine	Chemical	D013936
+12090760	CID	D015215	D000740
+
+7516729|t|Interactive effects of variations in [Na]o and [Ca]o on rat atrial spontaneous frequency.
+7516729|a|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)
+7516729	38	40	Na	Chemical	D012964
+7516729	48	50	Ca	Chemical	D002118
+7516729	149	151	Na	Chemical	D012964
+7516729	156	158	Ca	Chemical	D002118
+7516729	161	163	Na	Chemical	D012964
+7516729	171	173	Ca	Chemical	D002118
+7516729	250	259	verapamil	Chemical	D014700
+7516729	422	424	Na	Chemical	D012964
+7516729	437	439	Ca	Chemical	D002118
+7516729	484	486	Na	Chemical	D012964
+7516729	543	545	Na	Chemical	D012964
+7516729	562	564	Ca	Chemical	D002118
+7516729	616	618	Na	Chemical	D012964
+7516729	647	649	Ca	Chemical	D002118
+7516729	684	686	Na	Chemical	D012964
+7516729	735	737	Ca	Chemical	D002118
+7516729	805	807	Ca	Chemical	D002118
+7516729	920	931	bradycardia	Disease	D001919
+7516729	943	952	verapamil	Chemical	D014700
+7516729	1031	1033	Na	Chemical	D012964
+7516729	1038	1040	Ca	Chemical	D002118
+7516729	1082	1091	verapamil	Chemical	D014700
+7516729	1236	1245	verapamil	Chemical	D014700
+7516729	1438	1440	Na	Chemical	D012964
+7516729	1452	1454	Ca	Chemical	D002118
+7516729	1534	1543	verapamil	Chemical	D014700
+7516729	CID	D014700	D001919
+
+2802551|t|Sodium status influences chronic amphotericin B nephrotoxicity in rats.
+2802551|a|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.
+2802551	0	6	Sodium	Chemical	D012964
+2802551	33	47	amphotericin B	Chemical	D000666
+2802551	48	62	nephrotoxicity	Disease	D007674
+2802551	76	87	nephrotoxic	Disease	D007674
+2802551	101	115	amphotericin B	Chemical	D000666
+2802551	262	276	amphotericin B	Chemical	D000666
+2802551	287	297	creatinine	Chemical	D003404
+2802551	394	404	creatinine	Chemical	D003404
+2802551	493	503	creatinine	Chemical	D003404
+2802551	593	599	sodium	Chemical	D012964
+2802551	779	793	amphotericin B	Chemical	D000666
+2802551	922	936	amphotericin B	Chemical	D000666
+2802551	1204	1214	creatinine	Chemical	D003404
+2802551	1235	1249	amphotericin B	Chemical	D000666
+2802551	1277	1291	amphotericin B	Chemical	D000666
+2802551	1357	1363	sodium	Chemical	D012964
+2802551	CID	D000666	D007674
+
+19346865|t|Reversible inferior colliculus lesion in metronidazole-induced encephalopathy: magnetic resonance findings on diffusion-weighted and fluid attenuated inversion recovery imaging.
+19346865|a|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.
+19346865	11	37	inferior colliculus lesion	Disease	D001927
+19346865	41	54	metronidazole	Chemical	D008795
+19346865	63	77	encephalopathy	Disease	D001927
+19346865	219	246	inferior colliculus lesions	Disease	D001927
+19346865	250	263	metronidazole	Chemical	D008795
+19346865	272	286	encephalopathy	Disease	D001927
+19346865	511	524	metronidazole	Chemical	D008795
+19346865	533	547	encephalopathy	Disease	D001927
+19346865	595	608	metronidazole	Chemical	D008795
+19346865	678	687	infection	Disease	D007239
+19346865	999	1012	metronidazole	Chemical	D008795
+19346865	1869	1884	callosal lesion	Disease	D001927
+19346865	1920	1947	inferior colliculus lesions	Disease	D001927
+19346865	1994	2007	metronidazole	Chemical	D008795
+19346865	2016	2030	encephalopathy	Disease	D001927
+19346865	CID	D008795	D001927
+
+2334618|t|Comparison of the respiratory effects of i.v. infusions of morphine and regional analgesia by extradural block.
+2334618|a|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.
+2334618	59	67	morphine	Chemical	D009020
+2334618	155	161	apnoea	Disease	D001049
+2334618	237	245	morphine	Chemical	D009020
+2334618	331	342	bupivacaine	Chemical	D002045
+2334618	458	472	carbon dioxide	Chemical	D002245
+2334618	617	666	obstructive (P less than 0.05) and central apnoea	Disease	D020181|D020182	obstructive (P less than 0.05) apnoea|central apnoea
+2334618	733	741	morphine	Chemical	D009020
+2334618	789	805	tachyarrhythmias	Disease	D013610
+2334618	829	854	ventricular ectopic beats	Disease	D018879
+2334618	881	889	morphine	Chemical	D009020
+2334618	CID	D009020	D020182
+2334618	CID	D009020	D020181
+2334618	CID	D009020	D018879
+
+8864707|t|Magnetic resonance volumetry of the cerebellum in epileptic patients after phenytoin overdosages.
+8864707|a|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.
+8864707	50	59	epileptic	Disease	D004827
+8864707	75	84	phenytoin	Chemical	D010672
+8864707	85	96	overdosages	Disease	D062787
+8864707	161	170	phenytoin	Chemical	D010672
+8864707	186	204	cerebellar atrophy	Disease	D002526
+8864707	979	986	seizure	Disease	D012640
+8864707	1010	1019	phenytoin	Chemical	D010672
+8864707	1119	1128	phenytoin	Chemical	D010672
+8864707	1222	1231	phenytoin	Chemical	D010672
+8864707	1232	1242	overdosage	Disease	D062787
+8864707	1274	1292	cerebellar atrophy	Disease	D002526
+8864707	1317	1326	phenytoin	Chemical	D010672
+8864707	1360	1378	cerebellar atrophy	Disease	D002526
+8864707	1509	1529	cerebellar disorders	Disease	D002526
+8864707	CID	D010672	D062787
+
+12589964|t|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.
+12589964|a|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.
+12589964	60	77	myocardial damage	Disease	D009202
+12589964	81	92	doxorubicin	Chemical	D004317
+12589964	101	115	cardiomyopathy	Disease	D009202
+12589964	310	332	myocardial cell injury	Disease	D009202
+12589964	409	426	myocardial damage	Disease	D009202
+12589964	445	456	doxorubicin	Chemical	D004317
+12589964	458	461	DOX	Chemical	D004317
+12589964	471	485	cardiomyopathy	Disease	D009202
+12589964	573	590	cardiac disorders	Disease	D006331
+12589964	720	723	DOX	Chemical	D004317
+12589964	1125	1128	DOX	Chemical	D004317
+12589964	1227	1230	DOX	Chemical	D004317
+12589964	1268	1271	DOX	Chemical	D004317
+12589964	1323	1326	DOX	Chemical	D004317
+12589964	1360	1368	toxicity	Disease	D064420
+12589964	1526	1529	DOX	Chemical	D004317
+12589964	1650	1653	DOX	Chemical	D004317
+12589964	1723	1731	fibrosis	Disease	D005355
+12589964	1878	1886	fibrosis	Disease	D005355
+12589964	1928	1931	DOX	Chemical	D004317
+12589964	2111	2114	DOX	Chemical	D004317
+12589964	2185	2188	DOX	Chemical	D004317
+12589964	2289	2292	DOX	Chemical	D004317
+12589964	2693	2708	ischemic injury	Disease	D017202
+12589964	2715	2718	DOX	Chemical	D004317
+12589964	2771	2788	myocardial damage	Disease	D009202
+12589964	2930	2933	DOX	Chemical	D004317
+12589964	3064	3067	DOX	Chemical	D004317
+12589964	3221	3235	cardiotoxicity	Disease	D066126
+12589964	CID	D004317	D009202
+
+11263551|t|Calcineurin-inhibitor induced pain syndrome (CIPS): a severe disabling complication after organ transplantation.
+11263551|a|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.
+11263551	30	34	pain	Disease	D010146
+11263551	45	49	CIPS	Disease	-1
+11263551	118	122	pain	Disease	D010146
+11263551	272	276	pain	Disease	D010146
+11263551	304	308	pain	Disease	D010146
+11263551	491	509	bone marrow oedema	Disease	D001855|D004487	bone marrow|oedema
+11263551	532	536	Pain	Disease	D010146
+11263551	586	590	pain	Disease	D010146
+11263551	597	625	reflex sympathetic dystrophy	Disease	D012019
+11263551	627	641	polyneuropathy	Disease	D011115
+11263551	643	661	Morton's neuralgia	Disease	D009437
+11263551	663	667	gout	Disease	D006073
+11263551	669	681	osteoporosis	Disease	D010024
+11263551	683	701	avascular necrosis	Disease	D010020
+11263551	703	728	intermittent claudication	Disease	D007383
+11263551	742	758	foot deformities	Disease	D005530
+11263551	760	776	stress fractures	Disease	D015775
+11263551	782	801	hyperparathyroidism	Disease	D006961
+11263551	820	832	cyclosporine	Chemical	D016572
+11263551	837	847	tacrolimus	Chemical	D016559
+11263551	888	895	calcium	Chemical	D002118
+11263551	930	934	pain	Disease	D010146
+11263551	970	974	Pain	Disease	D010146
+11263551	985	989	CIPS	Disease	-1
+11263551	1027	1039	cyclosporine	Chemical	D016572
+11263551	1043	1053	tacrolimus	Chemical	D016559
+11263551	1270	1274	CIPS	Disease	-1
+11263551	CID	D016559	D010146
+11263551	CID	D016559	D004487
+11263551	CID	D016559	D001855
+11263551	CID	D016572	D001855
+11263551	CID	D016572	D004487
+11263551	CID	D016572	D010146
+
+10520387|t|The haemodynamic effects of propofol in combination with ephedrine in elderly patients (ASA groups 3 and 4).
+10520387|a|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.
+10520387	28	36	propofol	Chemical	D015742
+10520387	57	66	ephedrine	Chemical	D004809
+10520387	166	174	propofol	Chemical	D015742
+10520387	289	298	ephedrine	Chemical	D004809
+10520387	302	310	propofol	Chemical	D015742
+10520387	334	345	hypotensive	Disease	D007022
+10520387	410	419	ephedrine	Chemical	D004809
+10520387	433	441	propofol	Chemical	D015742
+10520387	559	568	ephedrine	Chemical	D004809
+10520387	572	580	propofol	Chemical	D015742
+10520387	632	643	hypotensive	Disease	D007022
+10520387	656	664	propofol	Chemical	D015742
+10520387	714	725	tachycardia	Disease	D013610
+10520387	753	762	ephedrine	Chemical	D004809
+10520387	783	791	propofol	Chemical	D015742
+10520387	912	923	tachycardia	Disease	D013610
+10520387	933	952	myocardial ischemia	Disease	D017202
+10520387	1019	1028	ephedrine	Chemical	D004809
+10520387	1029	1037	propofol	Chemical	D015742
+10520387	CID	D015742	D007022
+10520387	CID	D015742	D013610
+10520387	CID	D004809	D013610
+
+230316|t|Neurotoxicity of halogenated hydroxyquinolines: clinical analysis of cases reported outside Japan.
+230316|a|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.
+230316	0	13	Neurotoxicity	Disease	D020258
+230316	17	46	halogenated hydroxyquinolines	Chemical	D006912
+230316	149	159	neurotoxic	Disease	D020258
+230316	173	202	halogenated hydroxyquinolines	Chemical	D006912
+230316	354	364	clioquinol	Chemical	D007464
+230316	420	430	clioquinol	Chemical	D007464
+230316	520	544	neurological disturbance	Disease	D009422
+230316	578	592	encephalopathy	Disease	D001927
+230316	644	654	clioquinol	Chemical	D007464
+230316	750	763	optic atrophy	Disease	D009896
+230316	835	845	clioquinol	Chemical	D007464
+230316	863	891	acrodermatitis enteropathica	Disease	C538178
+230316	934	944	myelopathy	Disease	D013118
+230316	946	964	visual disturbance	Disease	D014786
+230316	970	991	peripheral neuropathy	Disease	D010523
+230316	1036	1046	myelopathy	Disease	D013118
+230316	1050	1071	peripheral neuropathy	Disease	D010523
+230316	1180	1194	encephalopathy	Disease	D001927
+230316	1334	1356	myelo-optic neuropathy	Disease	D013118|D009901	myelo neuropathy|optic neuropathy
+230316	CID	D007464	D001927
+230316	CID	D007464	D014786
+230316	CID	D007464	D010523
+230316	CID	D007464	D009896
+230316	CID	D007464	D013118
+
+11807648|t|Epileptic seizures following cortical application of fibrin sealants containing tranexamic acid in rats.
+11807648|a|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.
+11807648	0	18	Epileptic seizures	Disease	D004827
+11807648	80	95	tranexamic acid	Chemical	D014148
+11807648	356	371	tranexamic acid	Chemical	D014148
+11807648	373	378	tAMCA	Chemical	D014148
+11807648	440	445	tAMCA	Chemical	D014148
+11807648	470	488	epileptic seizures	Disease	D004827
+11807648	517	522	tAMCA	Chemical	D014148
+11807648	535	545	convulsive	Disease	D012640
+11807648	643	648	tAMCA	Chemical	D014148
+11807648	916	921	tAMCA	Chemical	D014148
+11807648	990	1000	convulsive	Disease	D012640
+11807648	1033	1041	seizures	Disease	D012640
+11807648	1085	1090	tAMCA	Chemical	D014148
+11807648	1123	1128	tAMCA	Chemical	D014148
+11807648	1136	1156	generalized seizures	Disease	D012640
+11807648	1216	1221	tAMCA	Chemical	D014148
+11807648	1280	1290	convulsive	Disease	D012640
+11807648	1410	1425	Tranexamic acid	Chemical	D014148
+11807648	1438	1448	convulsive	Disease	D012640
+11807648	1494	1499	tAMCA	Chemical	D014148
+11807648	CID	D014148	D012640
+
+14596845|t|A diet promoting sugar dependency causes behavioral cross-sensitization to a low dose of amphetamine.
+14596845|a|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.
+14596845	17	33	sugar dependency	Disease	D019966
+14596845	41	71	behavioral cross-sensitization	Disease	D006948
+14596845	89	100	amphetamine	Chemical	D000661
+14596845	272	287	drug dependency	Disease	D019966
+14596845	383	413	behavioral cross-sensitization	Disease	D006948
+14596845	431	442	amphetamine	Chemical	D000661
+14596845	599	606	sucrose	Chemical	D013395
+14596845	954	965	amphetamine	Chemical	D000661
+14596845	1019	1026	sucrose	Chemical	D013395
+14596845	1041	1052	hyperactive	Disease	D006948
+14596845	1068	1079	amphetamine	Chemical	D000661
+14596845	1130	1137	sucrose	Chemical	D013395
+14596845	1159	1170	amphetamine	Chemical	D000661
+14596845	1206	1217	amphetamine	Chemical	D000661
+14596845	1250	1261	amphetamine	Chemical	D000661
+14596845	1277	1284	sucrose	Chemical	D013395
+14596845	1521	1532	amphetamine	Chemical	D000661
+14596845	1578	1586	dopamine	Chemical	D004298
+14596845	CID	D013395	D006948
+14596845	CID	D000661	D006948
+
+6666578|t|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.
+6666578|a|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.
+6666578	0	15	D-penicillamine	Chemical	D010396
+6666578	24	34	angiopathy	Disease	D001018
+6666578	68	83	D-penicillamine	Chemical	D010396
+6666578	212	227	D-penicillamine	Chemical	D010396
+6666578	229	234	D-pen	Chemical	D010396
+6666578	659	664	D-pen	Chemical	D010396
+6666578	1103	1108	D-pen	Chemical	D010396
+6666578	1236	1247	hyaluronate	Chemical	D006820
+6666578	1298	1303	D-pen	Chemical	D010396
+6666578	1561	1566	D-pen	Chemical	D010396
+6666578	1654	1659	D-pen	Chemical	D010396
+6666578	CID	D010396	D001018
+
+11279304|t|Brain natriuretic peptide is a predictor of anthracycline-induced cardiotoxicity.
+11279304|a|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.
+11279304	44	57	anthracycline	Chemical	D018943
+11279304	66	80	cardiotoxicity	Disease	D066126
+11279304	82	96	Anthracyclines	Chemical	D018943
+11279304	172	186	cardiotoxicity	Disease	D066126
+11279304	192	206	cardiotoxicity	Disease	D066126
+11279304	223	236	anthracycline	Chemical	D018943
+11279304	337	356	cardiac dysfunction	Disease	D006331
+11279304	495	508	anthracycline	Chemical	D018943
+11279304	517	531	cardiotoxicity	Disease	D066126
+11279304	549	563	acute leukemia	Disease	D015470
+11279304	579	591	daunorubicin	Chemical	D003630
+11279304	593	596	DNR	Chemical	D003630
+11279304	641	655	acute leukemia	Disease	D015470
+11279304	676	679	DNR	Chemical	D003630
+11279304	928	952	congestive heart failure	Disease	D006333
+11279304	1042	1055	heart failure	Disease	D006333
+11279304	1169	1182	heart failure	Disease	D006333
+11279304	1275	1288	heart failure	Disease	D006333
+11279304	1382	1395	heart failure	Disease	D006333
+11279304	1402	1405	DNR	Chemical	D003630
+11279304	1536	1549	heart failure	Disease	D006333
+11279304	1647	1660	anthracycline	Chemical	D018943
+11279304	1669	1683	cardiotoxicity	Disease	D066126
+11279304	CID	D003630	D006333
+
+19884587|t|Antibacterial medication use during pregnancy and risk of birth defects: National Birth Defects Prevention Study.
+19884587|a|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.
+19884587	58	71	birth defects	Disease	D000014
+19884587	82	95	Birth Defects	Disease	D000014
+19884587	200	213	birth defects	Disease	D000014
+19884587	372	385	birth defects	Disease	D000014
+19884587	401	413	birth defect	Disease	D000014
+19884587	772	785	birth defects	Disease	D000014
+19884587	926	938	Sulfonamides	Chemical	D013449
+19884587	960	971	anencephaly	Disease	D000757
+19884587	1038	1069	hypoplastic left heart syndrome	Disease	D018636
+19884587	1100	1124	coarctation of the aorta	Disease	D001017
+19884587	1155	1170	choanal atresia	Disease	D002754
+19884587	1202	1228	transverse limb deficiency	Disease	D017880
+19884587	1263	1283	diaphragmatic hernia	Disease	D006548
+19884587	1314	1329	Nitrofurantoins	Chemical	D009582
+19884587	1351	1363	anophthalmia	Disease	D000853
+19884587	1367	1381	microphthalmos	Disease	D008850
+19884587	1413	1444	hypoplastic left heart syndrome	Disease	D018636
+19884587	1475	1496	atrial septal defects	Disease	D006344
+19884587	1531	1540	cleft lip	Disease	D002971
+19884587	1546	1558	cleft palate	Disease	D002972
+19884587	1650	1663	erythromycins	Chemical	D004917
+19884587	1677	1688	penicillins	Chemical	D010406
+19884587	1701	1715	cephalosporins	Chemical	D002511
+19884587	1732	1742	quinolones	Chemical	D015363
+19884587	1782	1793	penicillins	Chemical	D010406
+19884587	1795	1808	erythromycins	Chemical	D004917
+19884587	1814	1828	cephalosporins	Chemical	D002511
+19884587	1902	1915	birth defects	Disease	D000014
+19884587	1917	1929	Sulfonamides	Chemical	D013449
+19884587	1934	1949	nitrofurantoins	Chemical	D009582
+19884587	1979	1992	birth defects	Disease	D000014
+19884587	CID	D013449	D006548
+19884587	CID	D013449	D018636
+19884587	CID	D013449	D017880
+19884587	CID	D009582	D006344
+19884587	CID	D009582	D018636
+19884587	CID	D009582	D002972
+19884587	CID	D009582	D000853
+19884587	CID	D013449	D001017
+19884587	CID	D013449	D000014
+19884587	CID	D013449	D002754
+19884587	CID	D009582	D008850
+19884587	CID	D009582	D002971
+19884587	CID	D013449	D000757
+19884587	CID	D009582	D000014
+
+3970039|t|Incidence of neoplasms in patients with rheumatoid arthritis exposed to different treatment regimens.
+3970039|a|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.
+3970039	13	22	neoplasms	Disease	D009369
+3970039	40	60	rheumatoid arthritis	Disease	D001172
+3970039	203	223	rheumatoid arthritis	Disease	D001172
+3970039	253	269	cyclophosphamide	Chemical	D003520
+3970039	274	286	chlorambucil	Chemical	D002699
+3970039	288	305	alkylating agents	Chemical	D000477
+3970039	308	320	azathioprine	Chemical	D001379
+3970039	322	328	purine	Chemical	D011687
+3970039	344	356	methotrexate	Chemical	D008727
+3970039	358	368	folic acid	Chemical	D005492
+3970039	447	456	synovitis	Disease	D013585
+3970039	827	844	alkylating agents	Chemical	D000477
+3970039	886	915	acute nonlymphocytic leukemia	Disease	D015470
+3970039	926	943	alkylating agents	Chemical	D000477
+3970039	948	960	azathioprine	Chemical	D001379
+3970039	1000	1022	non-Hodgkin's lymphoma	Disease	D008228
+3970039	1024	1040	Cyclophosphamide	Chemical	D003520
+3970039	1071	1095	carcinoma of the bladder	Disease	D001749|D002277	carcinoma of the bladder|carcinoma
+3970039	1156	1176	rheumatoid arthritis	Disease	D001172
+3970039	1190	1202	azathioprine	Chemical	D001379
+3970039	1207	1223	cyclophosphamide	Chemical	D003520
+3970039	1264	1271	cancers	Disease	D009369
+3970039	1329	1339	malignancy	Disease	D009369
+3970039	1343	1363	rheumatoid arthritis	Disease	D001172
+3970039	1484	1501	alkylating agents	Chemical	D000477
+3970039	1523	1543	rheumatoid arthritis	Disease	D001172
+3970039	CID	D000477	D015470
+3970039	CID	D003520	D001749
+3970039	CID	D000477	D008228
+3970039	CID	D001379	D008228
+3970039	CID	D003520	D002277
+
+424937|t|Patterns of hepatic injury induced by methyldopa.
+424937|a|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.
+424937	12	26	hepatic injury	Disease	D056486
+424937	38	48	methyldopa	Chemical	D008750
+424937	71	84	liver disease	Disease	D008107
+424937	96	106	methyldopa	Chemical	D008750
+424937	334	342	Jaundice	Disease	D007565
+424937	355	367	hepatomegaly	Disease	D006529
+424937	410	418	anorexia	Disease	D000855
+424937	420	426	nausea	Disease	D009325
+424937	431	439	vomiting	Disease	D014839
+424937	467	481	abdominal pain	Disease	D015746
+424937	584	592	necrosis	Disease	D009336
+424937	643	657	hepatic injury	Disease	D056486
+424937	693	705	fatty change	Disease	D005234
+424937	731	739	necrosis	Disease	D009336
+424937	743	767	massive hepatic necrosis	Disease	D047508
+424937	809	824	acute hepatitis	Disease	D017114
+424937	828	852	chronic active hepatitis	Disease	D006521
+424937	869	880	cholestasis	Disease	D002779
+424937	1025	1040	hepatic failure	Disease	D017093
+424937	1075	1085	methyldopa	Chemical	D008750
+424937	1228	1247	fulminant hepatitis	Disease	D017114
+424937	1323	1333	methyldopa	Chemical	D008750
+424937	1342	1351	hepatitis	Disease	D056486
+424937	1426	1436	methyldopa	Chemical	D008750
+424937	1441	1460	hepatic dysfunction	Disease	D008107
+424937	1495	1504	hepatitis	Disease	D056486
+424937	CID	D008750	D009336
+424937	CID	D008750	D006529
+424937	CID	D008750	D009325
+424937	CID	D008750	D005234
+424937	CID	D008750	D014839
+424937	CID	D008750	D002779
+424937	CID	D008750	D015746
+424937	CID	D008750	D007565
+424937	CID	D008750	D056486
+424937	CID	D008750	D000855
+
+8643971|t|A phase I/II study of paclitaxel plus cisplatin as first-line therapy for head and neck cancers: preliminary results.
+8643971|a|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.
+8643971	22	32	paclitaxel	Chemical	D017239
+8643971	38	47	cisplatin	Chemical	D002945
+8643971	74	95	head and neck cancers	Disease	D006258
+8643971	156	180	head and neck carcinomas	Disease	D006258
+8643971	323	333	paclitaxel	Chemical	D017239
+8643971	335	340	Taxol	Chemical	D017239
+8643971	433	453	head and neck cancer	Disease	D006258
+8643971	463	473	paclitaxel	Chemical	D017239
+8643971	474	483	cisplatin	Chemical	D002945
+8643971	582	596	ovarian cancer	Disease	D010051
+8643971	669	677	toxicity	Disease	D064420
+8643971	692	702	paclitaxel	Chemical	D017239
+8643971	734	743	cisplatin	Chemical	D002945
+8643971	850	873	head and neck carcinoma	Disease	D006258
+8643971	981	986	tumor	Disease	D009369
+8643971	1172	1180	toxicity	Disease	D064420
+8643971	1305	1315	paclitaxel	Chemical	D017239
+8643971	1376	1385	cisplatin	Chemical	D002945
+8643971	1437	1447	paclitaxel	Chemical	D017239
+8643971	1527	1535	toxicity	Disease	D064420
+8643971	1684	1694	paclitaxel	Chemical	D017239
+8643971	2223	2231	Alopecia	Disease	D000505
+8643971	2233	2245	paresthesias	Disease	D010292
+8643971	2251	2262	arthralgias	Disease	D018771
+8643971	2263	2271	myalgias	Disease	D063806
+8643971	2332	2339	myalgia	Disease	D063806
+8643971	2399	2407	toxicity	Disease	D064420
+8643971	2423	2433	Paclitaxel	Chemical	D017239
+8643971	2434	2443	cisplatin	Chemical	D002945
+8643971	2507	2527	head and neck cancer	Disease	D006258
+8643971	2615	2625	paclitaxel	Chemical	D017239
+8643971	CID	D002945	D000505
+8643971	CID	D017239	D010292
+8643971	CID	D017239	D000505
+8643971	CID	D002945	D018771
+8643971	CID	D017239	D018771
+8643971	CID	D002945	D010292
+
+2224762|t|A phase I study of 4'-0-tetrahydropyranyladriamycin. Clinical pharmacology and pharmacokinetics.
+2224762|a|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.
+2224762	19	51	4'-0-tetrahydropyranyladriamycin	Chemical	C027260
+2224762	139	171	4'-0-tetrahydropyranyladriamycin	Chemical	C027260
+2224762	173	184	Pirarubicin	Chemical	C027260
+2224762	253	259	tumors	Disease	D009369
+2224762	367	399	renal and/or hepatic dysfunction	Disease	D007674|D008107	renal dysfunction|hepatic dysfunction
+2224762	622	638	granulocytopenia	Disease	D000380
+2224762	724	740	thrombocytopenia	Disease	D013921
+2224762	742	748	anemia	Disease	D000740
+2224762	750	756	nausea	Disease	D009325
+2224762	763	771	alopecia	Disease	D000505
+2224762	773	782	phlebitis	Disease	D010689
+2224762	788	797	mucositis	Disease	D052016
+2224762	799	815	Myelosuppression	Disease	D001855
+2224762	842	861	hepatic dysfunction	Disease	D008107
+2224762	912	923	Pirarubicin	Chemical	C027260
+2224762	1207	1219	Adriamycinol	Chemical	C010013
+2224762	1221	1232	doxorubicin	Chemical	D004317
+2224762	1234	1247	adriamycinone	Chemical	C010012
+2224762	1253	1282	tetrahydropyranyladriamycinol	Chemical	C027260
+2224762	1341	1352	doxorubicin	Chemical	D004317
+2224762	1430	1441	Pirarubicin	Chemical	C027260
+2224762	1517	1529	mesothelioma	Disease	D008654
+2224762	1531	1545	leiomyosarcoma	Disease	D007890
+2224762	1551	1571	basal cell carcinoma	Disease	D002280
+2224762	CID	D004317	D010689
+2224762	CID	D004317	D000380
+2224762	CID	D004317	D052016
+2224762	CID	D004317	D000505
+2224762	CID	D004317	D013921
+2224762	CID	D004317	D000740
+2224762	CID	D004317	D009325
+
+2440413|t|Differential effects of gamma-hexachlorocyclohexane (lindane) on pharmacologically-induced seizures.
+2440413|a|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.
+2440413	24	51	gamma-hexachlorocyclohexane	Chemical	D001556
+2440413	53	60	lindane	Chemical	D001556
+2440413	91	99	seizures	Disease	D012640
+2440413	101	128	Gamma-hexachlorocyclohexane	Chemical	D001556
+2440413	130	139	gamma-HCH	Chemical	D001556
+2440413	183	190	lindane	Chemical	D001556
+2440413	219	226	seizure	Disease	D012640
+2440413	257	260	PTZ	Chemical	D010433
+2440413	284	293	gamma-HCH	Chemical	D001556
+2440413	331	334	PTZ	Chemical	D010433
+2440413	343	351	seizures	Disease	D012640
+2440413	375	384	gamma-HCH	Chemical	D001556
+2440413	457	464	seizure	Disease	D012640
+2440413	560	569	gamma-HCH	Chemical	D001556
+2440413	608	617	gamma-HCH	Chemical	D001556
+2440413	635	642	seizure	Disease	D012640
+2440413	722	731	gamma-HCH	Chemical	D001556
+2440413	770	777	Seizure	Disease	D012640
+2440413	794	797	PTZ	Chemical	D010433
+2440413	802	812	picrotoxin	Chemical	D010852
+2440413	814	817	PTX	Chemical	D010852
+2440413	857	864	seizure	Disease	D012640
+2440413	881	905	3-mercaptopropionic acid	Chemical	D015097
+2440413	907	910	MPA	Chemical	D015097
+2440413	913	924	bicuculline	Chemical	D001640
+2440413	926	929	BCC	Chemical	D001640
+2440413	932	986	methyl 6,7-dimethoxy-4-ethyl-B-carboline-3-carboxylate	Chemical	C034818
+2440413	988	992	DMCM	Chemical	C034818
+2440413	998	1008	strychnine	Chemical	D013331
+2440413	1010	1013	STR	Chemical	D013331
+2440413	1057	1066	gamma-HCH	Chemical	D001556
+2440413	1068	1085	pentylenetetrazol	Chemical	D010433
+2440413	1090	1100	picrotoxin	Chemical	D010852
+2440413	1123	1130	3H-TBOB	Chemical	C046308
+2440413	1220	1223	MPA	Chemical	D015097
+2440413	1225	1228	BCC	Chemical	D001640
+2440413	1230	1234	DMCM	Chemical	C034818
+2440413	1240	1243	STR	Chemical	D013331
+2440413	1268	1275	3H-TBOB	Chemical	C046308
+2440413	1277	1306	t-butyl bicyclo-orthobenzoate	Chemical	C046308
+2440413	1420	1427	seizure	Disease	D012640
+2440413	1448	1451	PTZ	Chemical	D010433
+2440413	1456	1459	PTX	Chemical	D010852
+2440413	1471	1480	gamma-HCH	Chemical	D001556
+2440413	1519	1526	seizure	Disease	D012640
+2440413	1629	1636	seizure	Disease	D012640
+2440413	1657	1666	gamma-HCH	Chemical	D001556
+2440413	1678	1682	GABA	Chemical	D005680
+2440413	CID	C034818	D012640
+2440413	CID	D001640	D012640
+2440413	CID	D010433	D012640
+2440413	CID	D013331	D012640
+2440413	CID	D010852	D012640
+2440413	CID	D015097	D012640
+
+12483326|t|Severe ocular and orbital toxicity after intracarotid injection of carboplatin for recurrent glioblastomas.
+12483326|a|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.
+12483326	7	34	ocular and orbital toxicity	Disease	D005128|D009916	ocular toxicity|orbital toxicity
+12483326	67	78	carboplatin	Chemical	D016190
+12483326	93	106	glioblastomas	Disease	D005909
+12483326	120	132	Glioblastoma	Disease	D005909
+12483326	138	153	malignant tumor	Disease	D009369
+12483326	393	405	glioblastoma	Disease	D005909
+12483326	505	516	carboplatin	Chemical	D016190
+12483326	558	567	cisplatin	Chemical	D002945
+12483326	575	602	ocular and orbital toxicity	Disease	D005128|D009916	ocular toxicity|orbital toxicity
+12483326	660	687	ocular and orbital toxicity	Disease	D005128|D009916	ocular toxicity|orbital toxicity
+12483326	720	731	carboplatin	Chemical	D016190
+12483326	827	838	carboplatin	Chemical	D016190
+12483326	853	866	glioblastomas	Disease	D005909
+12483326	911	961	pain and visual disturbance in the ipsilateral eye	Disease	D058447|D014786	pain in the ipsilateral eye|visual disturbance in the ipsilateral eye
+12483326	1035	1046	carboplatin	Chemical	D016190
+12483326	1047	1055	toxicity	Disease	D064420
+12483326	1146	1154	glycerin	Chemical	D005990
+12483326	1271	1279	glaucoma	Disease	D005901
+12483326	1294	1305	ocular pain	Disease	D058447
+12483326	1329	1340	papilledema	Disease	D010211
+12483326	1355	1373	retinal detachment	Disease	D012163
+12483326	1429	1450	chorioretinal atrophy	Disease	C566236
+12483326	1456	1469	optic atrophy	Disease	D009896
+12483326	1574	1585	carboplatin	Chemical	D016190
+12483326	1632	1647	ocular toxicity	Disease	D005128
+12483326	CID	D016190	D009896
+12483326	CID	D016190	D010211
+12483326	CID	D016190	D012163
+12483326	CID	D016190	D058447
+12483326	CID	D016190	D014786
+12483326	CID	D016190	D009916
+
+1664218|t|Phase II study of the amsacrine analogue CI-921 (NSC 343499) in non-small cell lung cancer.
+1664218|a|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.
+1664218	22	31	amsacrine	Chemical	D000677
+1664218	41	47	CI-921	Chemical	C042315
+1664218	49	59	NSC 343499	Chemical	C042315
+1664218	64	90	non-small cell lung cancer	Disease	D002289
+1664218	92	98	CI-921	Chemical	C042315
+1664218	100	110	NSC 343499	Chemical	C042315
+1664218	112	202	9-[[2-methoxy-4-[(methylsulphonyl)amino]phenyl]amino] -N,5-dimethyl- 4-acridinecarboxamide	Chemical	C042315
+1664218	346	372	non-small cell lung cancer	Disease	D002289
+1664218	374	379	NSCLC	Disease	D002289
+1664218	663	681	squamous carcinoma	Disease	D002294
+1664218	688	702	adenocarcinoma	Disease	D000230
+1664218	729	756	bronchio-alveolar carcinoma	Disease	D002282
+1664218	776	802	undifferentiated carcinoma	Disease	D002277
+1664218	808	819	Neutropenia	Disease	D009503
+1664218	878	888	infections	Disease	D007239
+1664218	923	931	seizures	Disease	D012640
+1664218	976	982	nausea	Disease	D009325
+1664218	987	995	vomiting	Disease	D014839
+1664218	1024	1033	phlebitis	Disease	D010689
+1664218	1077	1100	squamous cell carcinoma	Disease	D002294
+1664218	1181	1187	tumour	Disease	D009369
+1664218	CID	C042315	D007239
+1664218	CID	C042315	D012640
+1664218	CID	C042315	D009503
+1664218	CID	C042315	D009325
+1664218	CID	C042315	D010689
+1664218	CID	C042315	D014839
+
+18809400|t|Alpha-lipoic acid prevents mitochondrial damage and neurotoxicity in experimental chemotherapy neuropathy.
+18809400|a|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.
+18809400	0	17	Alpha-lipoic acid	Chemical	D008063
+18809400	27	47	mitochondrial damage	Disease	D028361
+18809400	52	65	neurotoxicity	Disease	D020258
+18809400	95	105	neuropathy	Disease	D009422
+18809400	133	150	alpha-lipoic acid	Chemical	D008063
+18809400	199	212	neurotoxicity	Disease	D020258
+18809400	217	237	mitochondrial damage	Disease	D028361
+18809400	263	294	toxic neurodegenerative cascade	Disease	D009410
+18809400	330	347	alpha-lipoic acid	Chemical	D008063
+18809400	433	454	peripheral neuropathy	Disease	D010523
+18809400	574	584	paclitaxel	Chemical	D017239
+18809400	589	598	cisplatin	Chemical	D002945
+18809400	713	730	alpha-lipoic acid	Chemical	D008063
+18809400	745	758	axonal damage	Disease	D001480
+18809400	872	889	alpha-lipoic acid	Chemical	D008063
+18809400	925	934	cisplatin	Chemical	D002945
+18809400	939	949	paclitaxel	Chemical	D017239
+18809400	962	986	mitochondrial impairment	Disease	D028361
+18809400	1068	1085	Alpha-lipoic acid	Chemical	D008063
+18809400	1146	1159	neurotoxicity	Disease	D020258
+18809400	1195	1217	mitochondrial toxicity	Disease	D028361
+18809400	1351	1373	mitochondrial toxicity	Disease	D028361
+18809400	1407	1417	paclitaxel	Chemical	D017239
+18809400	1422	1431	cisplatin	Chemical	D002945
+18809400	1440	1453	neurotoxicity	Disease	D020258
+18809400	1455	1472	Alpha-lipoic acid	Chemical	D008063
+18809400	1637	1654	alpha-lipoic acid	Chemical	D008063
+18809400	1691	1716	peripheral nerve toxicity	Disease	D010523
+18809400	CID	D017239	D009410
+18809400	CID	D002945	D009410
+18809400	CID	D002945	D010523
+18809400	CID	D017239	D010523
+
+17020434|t|Optimising stroke prevention in non-valvular atrial fibrillation.
+17020434|a|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.
+17020434	11	17	stroke	Disease	D020521
+17020434	45	64	atrial fibrillation	Disease	D001281
+17020434	66	85	Atrial fibrillation	Disease	D001281
+17020434	230	238	warfarin	Chemical	D014859
+17020434	259	265	stroke	Disease	D020521
+17020434	283	290	aspirin	Chemical	D001241
+17020434	354	362	warfarin	Chemical	D014859
+17020434	378	385	aspirin	Chemical	D001241
+17020434	400	407	strokes	Disease	D020521
+17020434	448	460	Ximelagatran	Chemical	C426686
+17020434	529	538	vitamin K	Chemical	D014812
+17020434	577	591	embolic events	Disease	D004617
+17020434	636	659	abnormal liver function	Disease	D056486
+17020434	681	700	Atrial Fibrillation	Disease	D001281
+17020434	701	712	Clopidogrel	Chemical	C055162
+17020434	724	734	Irbesartan	Chemical	C081309
+17020434	798	806	warfarin	Chemical	D014859
+17020434	840	851	clopidogrel	Chemical	C055162
+17020434	857	864	aspirin	Chemical	D001241
+17020434	887	901	embolic events	Disease	D004617
+17020434	903	914	Idraparinux	Chemical	C479958
+17020434	975	994	atrial fibrillation	Disease	D001281
+17020434	996	1007	Angiotensin	Chemical	D000809
+17020434	1041	1055	angiotensin II	Chemical	D000804
+17020434	1096	1115	atrial fibrillation	Disease	D001281
+17020434	1124	1143	cardiac remodelling	Disease	D020257
+17020434	1178	1185	statins	Chemical	D019821
+17020434	CID	C426686	D056486
+
+3865016|t|Interaction of cyclosporin A with antineoplastic agents.
+3865016|a|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.
+3865016	15	28	cyclosporin A	Chemical	D016572
+3865016	81	90	etoposide	Chemical	D005047
+3865016	95	108	cyclosporin A	Chemical	D016572
+3865016	140	168	acute T-lymphocytic leukemia	Disease	D054218
+3865016	215	224	etoposide	Chemical	D005047
+3865016	229	242	cyclosporin A	Chemical	D016572
+3865016	290	311	leukemic infiltration	Disease	D017254
+3865016	367	376	confusion	Disease	D003221
+3865016	393	411	hyperbilirubinemia	Disease	D006932
+3865016	493	501	toxicity	Disease	D064420
+3865016	604	617	cyclosporin A	Chemical	D016572
+3865016	CID	D016572	D003221
+3865016	CID	D005047	D006932
+3865016	CID	D005047	D003221
+3865016	CID	D016572	D006932
+
+3629586|t|The hematologic effects of cefonicid and cefazedone in the dog: a potential model of cephalosporin hematotoxicity in man.
+3629586|a|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.
+3629586	27	36	cefonicid	Chemical	D015790
+3629586	41	51	cefazedone	Chemical	C021341
+3629586	85	98	cephalosporin	Chemical	D002511
+3629586	99	113	hematotoxicity	Disease	D006402
+3629586	122	135	Cephalosporin	Chemical	D002511
+3629586	167	191	hematologic disturbances	Disease	D006402
+3629586	338	354	blood dyscrasias	Disease	D006402
+3629586	388	396	toxicity	Disease	D064420
+3629586	440	449	cefonicid	Chemical	D015790
+3629586	453	463	cefazedone	Chemical	C021341
+3629586	516	522	anemia	Disease	D000740
+3629586	524	535	neutropenia	Disease	D009503
+3629586	541	557	thrombocytopenia	Disease	D013921
+3629586	607	613	anemia	Disease	D000740
+3629586	647	657	cytopenias	Disease	D006402
+3629586	724	733	cefonicid	Chemical	D015790
+3629586	751	761	cefazedone	Chemical	C021341
+3629586	773	783	cytopenias	Disease	D006402
+3629586	1036	1049	cephalosporin	Chemical	D002511
+3629586	1055	1075	hematologic syndrome	Disease	D006402
+3629586	1112	1121	cefonicid	Chemical	D015790
+3629586	1131	1141	cefazedone	Chemical	C021341
+3629586	1406	1415	hemolytic	Disease	D006461
+3629586	1530	1539	cytopenia	Disease	D006402
+3629586	1594	1603	cefonicid	Chemical	D015790
+3629586	1607	1617	cefazedone	Chemical	C021341
+3629586	1637	1651	hematotoxicity	Disease	D006402
+3629586	1667	1680	cephalosporin	Chemical	D002511
+3629586	1689	1705	blood dyscrasias	Disease	D006402
+3629586	CID	C021341	D009503
+3629586	CID	D015790	D013921
+3629586	CID	D015790	D000740
+3629586	CID	C021341	D013921
+3629586	CID	D015790	D009503
+3629586	CID	C021341	D000740
+
+150790|t|A pyridoxine-dependent behavioral disorder unmasked by isoniazid.
+150790|a|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.
+150790	2	12	pyridoxine	Chemical	D011736
+150790	23	42	behavioral disorder	Disease	D002653
+150790	55	64	isoniazid	Chemical	D007538
+150790	88	112	behavioral deterioration	Disease	D002653
+150790	119	131	hyperkinesis	Disease	D006948
+150790	133	145	irritability	Disease	D001523
+150790	151	172	sleeping difficulties	Disease	D012893
+150790	213	222	isoniazid	Chemical	D007538
+150790	269	293	pyridoxine hydrochloride	Chemical	D011736
+150790	350	359	isoniazid	Chemical	D007538
+150790	431	441	pyridoxine	Chemical	D011736
+150790	472	483	niacinamide	Chemical	D009536
+150790	504	514	pyridoxine	Chemical	D011736
+150790	539	549	pyridoxine	Chemical	D011736
+150790	584	596	hyperkinesis	Disease	D006948
+150790	611	620	pyridoxal	Chemical	D011730
+150790	719	729	kynurenine	Chemical	D007737
+150790	741	751	tryptophan	Chemical	D014364
+150790	848	858	pyridoxine	Chemical	D011736
+150790	CID	D007538	D006948
+150790	CID	D007538	D002653
+
+10579464|t|A selective dopamine D4 receptor antagonist, NRA0160: a preclinical neuropharmacological profile.
+10579464|a|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.
+10579464	12	20	dopamine	Chemical	D004298
+10579464	45	52	NRA0160	Chemical	C121249
+10579464	98	105	NRA0160	Chemical	C121249
+10579464	107	212	5 - [2- ( 4- ( 3 - fluorobenzylidene) piperidin-1-yl) ethyl] - 4 -(4-fluorophenyl) thiazole-2-carboxamide	Chemical	C121249
+10579464	251	259	dopamine	Chemical	D004298
+10579464	344	351	NRA0160	Chemical	C121249
+10579464	390	398	dopamine	Chemical	D004298
+10579464	444	452	dopamine	Chemical	D004298
+10579464	467	474	NRA0160	Chemical	C121249
+10579464	520	528	dopamine	Chemical	D004298
+10579464	557	566	serotonin	Chemical	D012701
+10579464	568	572	5-HT	Chemical	D012701
+10579464	639	646	NRA0160	Chemical	C121249
+10579464	651	660	clozapine	Chemical	D003024
+10579464	683	696	hyperactivity	Disease	D006948
+10579464	708	723	methamphetamine	Chemical	D008694
+10579464	725	728	MAP	Chemical	D008694
+10579464	739	746	NRA0160	Chemical	C121249
+10579464	751	760	clozapine	Chemical	D003024
+10579464	773	776	MAP	Chemical	D008694
+10579464	901	908	NRA0160	Chemical	C121249
+10579464	913	922	clozapine	Chemical	D003024
+10579464	945	954	catalepsy	Disease	D002375
+10579464	1048	1055	NRA0160	Chemical	C121249
+10579464	1060	1069	clozapine	Chemical	D003024
+10579464	1157	1168	apomorphine	Chemical	D001058
+10579464	1170	1177	NRA0160	Chemical	C121249
+10579464	1182	1191	clozapine	Chemical	D003024
+10579464	1220	1233	phencyclidine	Chemical	D010622
+10579464	1235	1238	PCP	Chemical	D010622
+10579464	1333	1340	NRA0160	Chemical	C121249
+10579464	CID	D008694	D006948
+10579464	CID	D003024	D002375
+10579464	CID	C121249	D002375
+
+3496378|t|Prolonged cholestasis after troleandomycin-induced acute hepatitis.
+3496378|a|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.
+3496378	10	21	cholestasis	Disease	D002779
+3496378	28	42	troleandomycin	Chemical	D014217
+3496378	57	66	hepatitis	Disease	D056486
+3496378	108	122	troleandomycin	Chemical	D014217
+3496378	131	140	hepatitis	Disease	D056486
+3496378	177	188	cholestasis	Disease	D002779
+3496378	190	198	Jaundice	Disease	D007565
+3496378	232	246	troleandomycin	Chemical	D014217
+3496378	282	299	hypereosinophilia	Disease	D004802
+3496378	301	309	Jaundice	Disease	D007565
+3496378	378	389	cholestasis	Disease	D002779
+3496378	400	408	pruritus	Disease	D011537
+3496378	499	507	pruritus	Disease	D011537
+3496378	602	611	hepatitis	Disease	D056486
+3496378	658	669	cholestasis	Disease	D002779
+3496378	681	695	troleandomycin	Chemical	D014217
+3496378	710	719	hepatitis	Disease	D056486
+3496378	CID	D014217	D002779
+3496378	CID	D014217	D007565
+3496378	CID	D014217	D004802
+3496378	CID	D014217	D011537
+3496378	CID	D014217	D056486
+
+3076126|t|HMG CoA reductase inhibitors. Current clinical experience.
+3076126|a|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.
+3076126	59	69	Lovastatin	Chemical	D008148
+3076126	74	85	simvastatin	Chemical	D019821
+3076126	217	227	lovastatin	Chemical	D008148
+3076126	328	339	simvastatin	Chemical	D019821
+3076126	422	432	Lovastatin	Chemical	D008148
+3076126	564	575	cholesterol	Chemical	D002784
+3076126	599	610	cholesterol	Chemical	D002784
+3076126	663	674	cholesterol	Chemical	D002784
+3076126	1254	1262	creatine	Chemical	D003401
+3076126	1315	1323	Myopathy	Disease	D009135
+3076126	1355	1368	myoglobinuria	Disease	D009212
+3076126	1400	1413	renal failure	Disease	D051437
+3076126	1445	1455	lovastatin	Chemical	D008148
+3076126	1507	1518	cyclosporin	Chemical	D016572
+3076126	1520	1531	gemfibrozil	Chemical	D015248
+3076126	1535	1541	niacin	Chemical	D009525
+3076126	1543	1553	Lovastatin	Chemical	D008148
+3076126	1558	1569	simvastatin	Chemical	D019821
+3076126	1653	1664	cholesterol	Chemical	D002784
+3076126	1778	1799	hypercholesterolaemia	Disease	D006937
+3076126	CID	D015248	D009135
+3076126	CID	D016572	D009135
+3076126	CID	D008148	D051437
+3076126	CID	D009525	D009135
+3076126	CID	D008148	D009212
+
+2894766|t|Sulfasalazine-induced lupus erythematosus.
+2894766|a|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.
+2894766	0	13	Sulfasalazine	Chemical	D012460
+2894766	22	41	lupus erythematosus	Disease	D008180
+2894766	43	54	Pneumonitis	Disease	D011014
+2894766	66	83	pleural effusions	Disease	D010996
+2894766	115	132	cardiac tamponade	Disease	D002305
+2894766	222	235	sulfasalazine	Chemical	D012460
+2894766	256	274	ulcerative colitis	Disease	D003093
+2894766	299	312	sulfasalazine	Chemical	D012460
+2894766	467	480	sulfasalazine	Chemical	D012460
+2894766	489	494	lupus	Disease	D008180
+2894766	518	527	serositis	Disease	D012700
+2894766	619	632	sulfasalazine	Chemical	D012460
+2894766	656	682	inflammatory bowel disease	Disease	D015212
+2894766	715	728	sulfasalazine	Chemical	D012460
+2894766	737	751	lupus syndrome	Disease	D008180
+2894766	CID	D012460	D010996
+2894766	CID	D012460	D011014
+2894766	CID	D012460	D008180
+2894766	CID	D012460	D002305
+
+1549199|t|Optimization of levodopa therapy.
+1549199|a|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.
+1549199	16	24	levodopa	Chemical	D007980
+1549199	85	93	levodopa	Chemical	D007980
+1549199	240	249	carbidopa	Chemical	D002230
+1549199	250	258	levodopa	Chemical	D007980
+1549199	306	314	toxicity	Disease	D064420
+1549199	627	635	dopamine	Chemical	D004298
+1549199	685	711	gastrointestinal disorders	Disease	D005767
+1549199	713	736	orthostatic hypotension	Disease	D007024
+1549199	738	746	levodopa	Chemical	D007980
+1549199	755	764	psychosis	Disease	D011618
+1549199	766	784	sleep disturbances	Disease	D012893
+1549199	788	799	parasomnias	Disease	D020447
+1549199	917	936	Parkinson's disease	Disease	D010300
+1549199	CID	D007980	D020447
+1549199	CID	D007980	D005767
+1549199	CID	D007980	D007024
+
+88336|t|Alpha and beta coma in drug intoxication uncomplicated by cerebral hypoxia.
+88336|a|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.
+88336	15	19	coma	Disease	D003128
+88336	58	74	cerebral hypoxia	Disease	D002534
+88336	108	116	comatose	Disease	D003128
+88336	120	129	stuporous	Disease	D053608
+88336	231	246	chlormethiazole	Chemical	D002719
+88336	251	258	alcohol	Chemical	D000431
+88336	259	278	withdrawal symptoms	Disease	D013375
+88336	304	312	overdose	Disease	D062787
+88336	316	326	nitrazepam	Chemical	D009567
+88336	345	355	nitrazepam	Chemical	D009567
+88336	356	364	overdose	Disease	D062787
+88336	387	402	chlormethiazole	Chemical	D002719
+88336	452	456	coma	Disease	D003128
+88336	589	604	chlormethiazole	Chemical	D002719
+88336	725	746	neurological sequelae	Disease	D009422
+88336	876	886	depression	Disease	D003866
+88336	1064	1068	coma	Disease	D003128
+88336	1209	1219	hypoxaemia	Disease	D000860
+88336	CID	D002719	D003128
+88336	CID	D009567	D003128
+88336	CID	D002719	D053608
+88336	CID	D009567	D062787
+
+18544179|t|Omitting fentanyl reduces nausea and vomiting, without increasing pain, after sevoflurane for day surgery.
+18544179|a|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.
+18544179	9	17	fentanyl	Chemical	D005283
+18544179	26	32	nausea	Disease	D009325
+18544179	37	45	vomiting	Disease	D014839
+18544179	66	70	pain	Disease	D010146
+18544179	78	89	sevoflurane	Chemical	C009250
+18544179	201	212	sevoflurane	Chemical	C009250
+18544179	214	247	postoperative nausea and vomiting	Disease	D020250
+18544179	267	275	Fentanyl	Chemical	D005283
+18544179	447	480	postoperative nausea and vomiting	Disease	D020250
+18544179	485	489	pain	Disease	D010146
+18544179	514	525	sevoflurane	Chemical	C009250
+18544179	643	651	fentanyl	Chemical	D005283
+18544179	682	695	dexamethasone	Chemical	D003907
+18544179	711	719	fentanyl	Chemical	D005283
+18544179	742	750	fentanyl	Chemical	D005283
+18544179	791	824	postoperative nausea and vomiting	Disease	D020250
+18544179	858	866	vomiting	Disease	D014839
+18544179	893	899	nausea	Disease	D009325
+18544179	941	949	fentanyl	Chemical	D005283
+18544179	954	962	fentanyl	Chemical	D005283
+18544179	963	976	dexamethasone	Chemical	D003907
+18544179	1085	1098	Dexamethasone	Chemical	D003907
+18544179	1157	1190	postoperative nausea and vomiting	Disease	D020250
+18544179	1210	1218	fentanyl	Chemical	D005283
+18544179	1304	1337	postoperative nausea and vomiting	Disease	D020250
+18544179	1342	1348	nausea	Disease	D009325
+18544179	1447	1453	nausea	Disease	D009325
+18544179	1515	1519	Pain	Disease	D010146
+18544179	1591	1599	fentanyl	Chemical	D005283
+18544179	1601	1609	Fentanyl	Chemical	D005283
+18544179	1662	1673	sevoflurane	Chemical	C009250
+18544179	1703	1725	respiratory depression	Disease	D012131
+18544179	1727	1738	hypotension	Disease	D007022
+18544179	1743	1754	bradycardia	Disease	D001919
+18544179	1771	1779	fentanyl	Chemical	D005283
+18544179	1792	1825	postoperative nausea and vomiting	Disease	D020250
+18544179	1852	1870	postoperative pain	Disease	D010149
+18544179	1990	2001	sevoflurane	Chemical	C009250
+18544179	CID	D005283	D007022
+18544179	CID	D005283	D012131
+18544179	CID	D005283	D020250
+18544179	CID	D005283	D001919
+
+18186898|t|Renal Fanconi syndrome and myopathy after liver transplantation: drug-related mitochondrial cytopathy?
+18186898|a|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.
+18186898	0	22	Renal Fanconi syndrome	Disease	D005198
+18186898	27	35	myopathy	Disease	D009135
+18186898	78	101	mitochondrial cytopathy	Disease	C540770
+18186898	444	460	Wilson's disease	Disease	D006527
+18186898	462	472	Tacrolimus	Chemical	D016559
+18186898	474	477	MMF	Chemical	-1
+18186898	483	491	steroids	Chemical	D013256
+18186898	525	535	Lamivudine	Chemical	D019259
+18186898	565	586	hepatitis B infection	Disease	D006509
+18186898	654	676	renal Fanconi syndrome	Disease	D005198
+18186898	689	707	metabolic acidosis	Disease	D000138
+18186898	709	725	hypophosphatemia	Disease	D017674
+18186898	727	737	glycosuria	Disease	D006029
+18186898	743	756	aminoaciduria	Disease	D000608
+18186898	767	777	tacrolimus	Chemical	D016559
+18186898	838	846	acidosis	Disease	D000138
+18186898	867	876	sirolimus	Chemical	D020123
+18186898	878	886	acidosis	Disease	D000138
+18186898	934	949	muscle weakness	Disease	D018908
+18186898	986	1002	Fanconi syndrome	Disease	D005198
+18186898	1015	1023	myopathy	Disease	D009135
+18186898	1061	1084	mitochondrial disorders	Disease	D028361
+18186898	1149	1168	tubular dysfunction	Disease	D005198
+18186898	1173	1181	myopathy	Disease	D009135
+18186898	1205	1230	mitochondrial dysfunction	Disease	D028361
+18186898	1253	1263	tacrolimus	Chemical	D016559
+18186898	1281	1291	lamivudine	Chemical	D019259
+18186898	CID	D016559	D005198
+18186898	CID	D016559	D009135
+18186898	CID	D019259	D009135
+18186898	CID	D019259	D005198
+
+16867021|t|Antipsychotic-like profile of thioperamide, a selective H3-receptor antagonist in mice.
+16867021|a|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.
+16867021	30	42	thioperamide	Chemical	C052075
+16867021	195	208	schizophrenia	Disease	D012559
+16867021	264	273	histamine	Chemical	D006632
+16867021	319	328	catalepsy	Disease	D002375
+16867021	330	341	apomorphine	Chemical	D001058
+16867021	372	383	amphetamine	Chemical	D000661
+16867021	422	431	Catalepsy	Disease	D002375
+16867021	447	458	haloperidol	Chemical	D006220
+16867021	481	492	apomorphine	Chemical	D001058
+16867021	514	525	amphetamine	Chemical	D000661
+16867021	622	647	(R)-alpha-methylhistamine	Chemical	C069357
+16867021	649	653	RAMH	Chemical	C069357
+16867021	677	689	thioperamide	Chemical	C052075
+16867021	691	694	THP	Chemical	C052075
+16867021	734	743	catalepsy	Disease	D002375
+16867021	763	766	THP	Chemical	C052075
+16867021	810	821	haloperidol	Chemical	D006220
+16867021	867	876	catalepsy	Disease	D002375
+16867021	922	926	RAMH	Chemical	C069357
+16867021	968	971	THP	Chemical	C052075
+16867021	989	993	RAMH	Chemical	C069357
+16867021	1089	1092	THP	Chemical	C052075
+16867021	1154	1165	amphetamine	Chemical	D000661
+16867021	1174	1187	hyperactivity	Disease	D006948
+16867021	1189	1192	THP	Chemical	C052075
+16867021	1309	1313	RAMH	Chemical	C069357
+16867021	1372	1375	THP	Chemical	C052075
+16867021	1424	1435	apomorphine	Chemical	D001058
+16867021	1472	1475	THP	Chemical	C052075
+16867021	1530	1534	RAMH	Chemical	C069357
+16867021	1536	1539	THP	Chemical	C052075
+16867021	1596	1607	haloperidol	Chemical	D006220
+16867021	1616	1625	catalepsy	Disease	D002375
+16867021	1636	1647	amphetamine	Chemical	D000661
+16867021	1656	1669	hyperactivity	Disease	D006948
+16867021	1683	1694	apomorphine	Chemical	D001058
+16867021	1737	1740	THP	Chemical	C052075
+16867021	1758	1762	RAMH	Chemical	C069357
+16867021	1793	1802	histamine	Chemical	D006632
+16867021	1915	1928	schizophrenia	Disease	D012559
+16867021	CID	D000661	D006948
+16867021	CID	D006220	D002375
+16867021	CID	C052075	D002375
+
+14976857|t|Transient platypnea-orthodeoxia-like syndrome induced by propafenone overdose in a young woman with Ebstein's anomaly.
+14976857|a|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.
+14976857	10	45	platypnea-orthodeoxia-like syndrome	Disease	-1
+14976857	57	68	propafenone	Chemical	D011405
+14976857	69	77	overdose	Disease	D062787
+14976857	100	117	Ebstein's anomaly	Disease	D004437
+14976857	189	206	Ebstein's anomaly	Disease	D004437
+14976857	245	266	platypnea-orthodeoxia	Disease	-1
+14976857	352	359	hypoxia	Disease	D000860
+14976857	364	372	cyanosis	Disease	D003490
+14976857	400	420	patent foramen ovale	Disease	D054092
+14976857	520	531	propafenone	Chemical	D011405
+14976857	532	540	overdose	Disease	D062787
+14976857	559	584	biventricular dysfunction	Disease	D018754
+14976857	628	639	hypotension	Disease	D007022
+14976857	CID	D011405	D018754
+14976857	CID	D011405	D000860
+14976857	CID	D011405	D003490
+
+11745184|t|A Phase II trial of cisplatin plus WR-2721 (amifostine) for metastatic breast carcinoma: an Eastern Cooperative Oncology Group Study (E8188).
+11745184|a|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.
+11745184	20	29	cisplatin	Chemical	D002945
+11745184	35	42	WR-2721	Chemical	D004999
+11745184	44	54	amifostine	Chemical	D004999
+11745184	71	87	breast carcinoma	Disease	D001943
+11745184	154	163	Cisplatin	Chemical	D002945
+11745184	254	270	breast carcinoma	Disease	D001943
+11745184	348	357	cisplatin	Chemical	D002945
+11745184	446	455	cisplatin	Chemical	D002945
+11745184	475	485	toxicities	Disease	D064420
+11745184	502	511	cisplatin	Chemical	D002945
+11745184	519	533	nephrotoxicity	Disease	D007674
+11745184	535	546	ototoxicity	Disease	D006311
+11745184	552	565	neurotoxicity	Disease	D020258
+11745184	607	623	breast carcinoma	Disease	D001943
+11745184	625	632	WR-2721	Chemical	D004999
+11745184	636	646	amifostine	Chemical	D004999
+11745184	730	740	Amifostine	Chemical	D004999
+11745184	816	833	alkylating agents	Chemical	D000477
+11745184	838	847	cisplatin	Chemical	D002945
+11745184	925	934	cisplatin	Chemical	D002945
+11745184	939	949	amifostine	Chemical	D004999
+11745184	1000	1009	cisplatin	Chemical	D002945
+11745184	1018	1032	nephrotoxicity	Disease	D007674
+11745184	1034	1045	ototoxicity	Disease	D006311
+11745184	1051	1061	neuropathy	Disease	D009422
+11745184	1124	1133	cisplatin	Chemical	D002945
+11745184	1139	1149	amifostine	Chemical	D004999
+11745184	1204	1220	breast carcinoma	Disease	D001943
+11745184	1329	1339	amifostine	Chemical	D004999
+11745184	1406	1416	amifostine	Chemical	D004999
+11745184	1427	1436	cisplatin	Chemical	D002945
+11745184	1507	1515	mannitol	Chemical	D008353
+11745184	1550	1559	cisplatin	Chemical	D002945
+11745184	1940	1959	Neurologic toxicity	Disease	D020258
+11745184	2026	2036	toxicities	Disease	D064420
+11745184	2122	2131	cisplatin	Chemical	D002945
+11745184	2136	2146	amifostine	Chemical	D004999
+11745184	2216	2221	tumor	Disease	D009369
+11745184	2252	2260	toxicity	Disease	D064420
+11745184	2313	2323	amifostine	Chemical	D004999
+11745184	2327	2336	cisplatin	Chemical	D002945
+11745184	CID	D002945	D009422
+11745184	CID	D002945	D006311
+11745184	CID	D002945	D007674
+
+3985451|t|Warfarin-induced iliopsoas hemorrhage with subsequent femoral nerve palsy.
+3985451|a|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.
+3985451	0	8	Warfarin	Chemical	D014859
+3985451	27	37	hemorrhage	Disease	D006470
+3985451	54	73	femoral nerve palsy	Disease	D020428
+3985451	127	135	warfarin	Chemical	D014859
+3985451	166	177	muscle tear	Disease	D009135
+3985451	203	207	pain	Disease	D010146
+3985451	222	233	contracture	Disease	D003286
+3985451	295	303	hematoma	Disease	D006406
+3985451	316	332	nerve entrapment	Disease	D009408
+3985451	349	368	femoral nerve palsy	Disease	D020428
+3985451	373	409	partial loss of quadriceps functions	Disease	D009135
+3985451	433	452	femoral nerve palsy	Disease	D020428
+3985451	488	496	warfarin	Chemical	D014859
+3985451	505	526	peripheral neuropathy	Disease	D010523
+3985451	558	562	pain	Disease	D010146
+3985451	606	634	motor and sensory impairment	Disease	D015417
+3985451	648	659	contracture	Disease	D003286
+3985451	CID	D014859	D020428
+3985451	CID	D014859	D009408
+3985451	CID	D014859	D009135
+3985451	CID	D014859	D006406
+
+3750012|t|Myasthenia gravis caused by penicillamine and chloroquine therapy for rheumatoid arthritis.
+3750012|a|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.
+3750012	0	17	Myasthenia gravis	Disease	D009157
+3750012	28	41	penicillamine	Chemical	D010396
+3750012	46	57	chloroquine	Chemical	D002738
+3750012	70	90	rheumatoid arthritis	Disease	D001172
+3750012	163	180	myasthenia gravis	Disease	D009157
+3750012	187	200	penicillamine	Chemical	D010396
+3750012	205	216	chloroquine	Chemical	D002738
+3750012	229	249	rheumatoid arthritis	Disease	D001172
+3750012	260	273	acetylcholine	Chemical	D000109
+3750012	CID	D002738	D009157
+3750012	CID	D010396	D009157
+
+1130930|t|Nephrotoxicity of combined cephalothin-gentamicin regimen.
+1130930|a|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.
+1130930	0	14	Nephrotoxicity	Disease	D007674
+1130930	27	38	cephalothin	Chemical	D002512
+1130930	39	49	gentamicin	Chemical	D005839
+1130930	82	104	acute tubular necrosis	Disease	D007683
+1130930	140	162	oliguric renal failure	Disease	D009846|D051437	oliguric|renal failure
+1130930	207	225	cephalothin sodium	Chemical	D002512
+1130930	230	248	gentamicin sulfate	Chemical	D005839
+1130930	352	366	nephrotoxicity	Disease	D007674
+1130930	474	493	renal insufficiency	Disease	D051437
+1130930	CID	D005839	D007683
+1130930	CID	D002512	D007683
+1130930	CID	D005839	D009846
+1130930	CID	D002512	D009846
+
+19356307|t|Components of lemon essential oil attenuate dementia induced by scopolamine.
+19356307|a|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.
+19356307	44	52	dementia	Disease	D003704
+19356307	64	75	scopolamine	Chemical	D012601
+19356307	86	94	dementia	Disease	D003704
+19356307	106	116	s-limonene	Chemical	C008281
+19356307	121	139	s-perillyl alcohol	Chemical	C032208
+19356307	295	310	memory impaired	Disease	D008569
+19356307	314	325	scopolamine	Chemical	D012601
+19356307	336	354	s-perillyl alcohol	Chemical	C032208
+19356307	368	397	deficit of associative memory	Disease	D008569
+19356307	568	576	dopamine	Chemical	D004298
+19356307	606	617	scopolamine	Chemical	D012601
+19356307	726	736	s-limonene	Chemical	C008281
+19356307	740	758	s-perillyl alcohol	Chemical	C032208
+19356307	801	812	scopolamine	Chemical	D012601
+19356307	CID	D012601	D008569
+
+15957009|t|The selective 5-HT6 receptor antagonist Ro4368554 restores memory performance in cholinergic and serotonergic models of memory deficiency in the rat.
+15957009|a|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.
+15957009	40	49	Ro4368554	Chemical	C507242
+15957009	120	137	memory deficiency	Disease	D008569
+15957009	165	174	serotonin	Chemical	D012701
+15957009	183	187	5-HT	Chemical	D012701
+15957009	353	366	acetylcholine	Chemical	D000109
+15957009	368	371	ACh	Chemical	D000109
+15957009	461	465	5-HT	Chemical	D012701
+15957009	480	489	Ro4368554	Chemical	C507242
+15957009	491	545	3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole	Chemical	C507242
+15957009	605	616	scopolamine	Chemical	D012601
+15957009	652	662	tryptophan	Chemical	D014364
+15957009	664	667	TRP	Chemical	D014364
+15957009	780	791	metrifonate	Chemical	D014236
+15957009	909	920	metrifonate	Chemical	D014236
+15957009	985	994	Ro4368554	Chemical	C507242
+15957009	1015	1024	Ro4368554	Chemical	C507242
+15957009	1072	1083	metrifonate	Chemical	D014236
+15957009	1124	1139	memory deficits	Disease	D008569
+15957009	1151	1162	scopolamine	Chemical	D012601
+15957009	1167	1170	TRP	Chemical	D014364
+15957009	1256	1265	Ro4368554	Chemical	C507242
+15957009	1361	1375	memory deficit	Disease	D008569
+15957009	1465	1474	Ro4368554	Chemical	C507242
+15957009	1496	1500	5-HT	Chemical	D012701
+15957009	CID	D012601	D008569
+
+15899738|t|Lone atrial fibrillation associated with creatine monohydrate supplementation.
+15899738|a|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.
+15899738	5	24	atrial fibrillation	Disease	D001281
+15899738	41	49	creatine	Chemical	D003401
+15899738	79	98	Atrial fibrillation	Disease	D001281
+15899738	136	149	heart disease	Disease	D006331
+15899738	179	189	arrhythmia	Disease	D001145
+15899738	272	289	Thyroid disorders	Disease	D013959
+15899738	326	352	acute alcohol intoxication	Disease	D000435
+15899738	467	486	atrial fibrillation	Disease	D001281
+15899738	575	584	fractures	Disease	D050723
+15899738	639	648	magnesium	Chemical	D008274
+15899738	654	663	potassium	Chemical	D011188
+15899738	734	741	alcohol	Chemical	D000431
+15899738	856	864	creatine	Chemical	D003401
+15899738	968	975	heparin	Chemical	D006493
+15899738	999	1008	diltiazem	Chemical	D004110
+15899738	1042	1052	amiodarone	Chemical	D000638
+15899738	1141	1151	metoprolol	Chemical	D008790
+15899738	1156	1163	aspirin	Chemical	D001241
+15899738	1258	1266	creatine	Chemical	D003401
+15899738	1360	1368	creatine	Chemical	D003401
+15899738	1491	1499	creatine	Chemical	D003401
+15899738	1522	1532	arrhythmia	Disease	D001145
+15899738	CID	D003401	D001281
+
+15863244|t|Comparison of developmental toxicity of selective and non-selective cyclooxygenase-2 inhibitors in CRL:(WI)WUBR Wistar rats--DFU and piroxicam study.
+15863244|a|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.
+15863244	28	36	toxicity	Disease	D064420
+15863244	125	128	DFU	Chemical	C106876
+15863244	133	142	piroxicam	Chemical	D010894
+15863244	268	276	toxicity	Disease	D064420
+15863244	409	417	toxicity	Disease	D064420
+15863244	440	449	piroxicam	Chemical	D010894
+15863244	466	469	DFU	Chemical	C106876
+15863244	471	545	5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanon	Chemical	C106876
+15863244	716	725	piroxicam	Chemical	D010894
+15863244	757	760	DFU	Chemical	C106876
+15863244	919	968	ventricular septal (VSD) and midline (MD) defects	Disease	D006345|D009436	ventricular septal (VSD) defects|midline (MD) defects
+15863244	1010	1019	piroxicam	Chemical	D010894
+15863244	1119	1127	toxicity	Disease	D064420
+15863244	1129	1160	intrauterine growth retardation	Disease	D005317
+15863244	1166	1210	increase of external and skeletal variations	Disease	D009139
+15863244	1263	1272	piroxicam	Chemical	D010894
+15863244	1325	1328	DFU	Chemical	C106876
+15863244	1343	1351	toxicity	Disease	D064420
+15863244	1443	1452	piroxicam	Chemical	D010894
+15863244	1457	1460	DFU	Chemical	C106876
+15863244	1771	1774	DFU	Chemical	C106876
+15863244	1776	1785	piroxicam	Chemical	D010894
+15863244	1899	1937	ventricular septal and midline defects	Disease	D006345|D009436	ventricular septal defects|midline defects
+15863244	CID	D010894	D005317
+15863244	CID	D010894	D009139
+15863244	CID	C106876	D005317
+
+12921865|t|Protective efficacy of neuroactive steroids against cocaine kindled-seizures in mice.
+12921865|a|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.
+12921865	35	43	steroids	Chemical	D013256
+12921865	52	59	cocaine	Chemical	D003042
+12921865	68	76	seizures	Disease	D012640
+12921865	98	106	steroids	Chemical	D013256
+12921865	177	215	neurological and psychiatric disorders	Disease	D009422|D001523	neurological disorders|psychiatric disorders
+12921865	247	255	seizures	Disease	D012640
+12921865	315	330	drug dependence	Disease	D019966
+12921865	447	454	steroid	Chemical	D013256
+12921865	484	507	gamma-aminobutyric acid	Chemical	D005680
+12921865	509	513	GABA	Chemical	D005680
+12921865	592	599	cocaine	Chemical	D003042
+12921865	623	630	cocaine	Chemical	D003042
+12921865	647	654	seizure	Disease	D012640
+12921865	666	682	Allopregnanolone	Chemical	D011280
+12921865	684	720	3alpha-hydroxy-5alpha-pregnan-20-one	Chemical	D011280
+12921865	723	735	pregnanolone	Chemical	D011280
+12921865	737	772	3alpha-hydroxy-5beta-pregnan-20-one	Chemical	D011280
+12921865	778	788	ganaxolone	Chemical	C105051
+12921865	816	832	allopregnanolone	Chemical	D011280
+12921865	833	882	3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one	Chemical	C105051
+12921865	1011	1018	cocaine	Chemical	D003042
+12921865	1027	1035	seizures	Disease	D012640
+12921865	1073	1081	seizures	Disease	D012640
+12921865	1131	1138	cocaine	Chemical	D003042
+12921865	1173	1177	GABA	Chemical	D005680
+12921865	1229	1237	seizures	Disease	D012640
+12921865	1252	1268	allopregnanolone	Chemical	D011280
+12921865	1273	1283	ganaxolone	Chemical	C105051
+12921865	1323	1339	Allopregnanolone	Chemical	D011280
+12921865	1344	1356	pregnanolone	Chemical	D011280
+12921865	1366	1376	ganaxolone	Chemical	C105051
+12921865	1487	1495	steroids	Chemical	D013256
+12921865	1547	1554	cocaine	Chemical	D003042
+12921865	CID	D003042	D012640
+
+12584269|t|Kidney function and morphology after short-term combination therapy with cyclosporine A, tacrolimus and sirolimus in the rat.
+12584269|a|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.
+12584269	73	87	cyclosporine A	Chemical	D016572
+12584269	89	99	tacrolimus	Chemical	D016559
+12584269	104	113	sirolimus	Chemical	D020123
+12584269	138	147	Sirolimus	Chemical	D020123
+12584269	149	152	SRL	Chemical	D020123
+12584269	237	248	nephrotoxic	Disease	D007674
+12584269	254	257	SRL	Chemical	D020123
+12584269	305	316	nephrotoxic	Disease	D007674
+12584269	405	408	SRL	Chemical	D020123
+12584269	480	491	nephrotoxic	Disease	D007674
+12584269	676	690	cyclosporine A	Chemical	D016572
+12584269	692	695	CsA	Chemical	D016572
+12584269	698	708	tacrolimus	Chemical	D016559
+12584269	710	715	FK506	Chemical	D016559
+12584269	720	723	SRL	Chemical	D020123
+12584269	805	808	CsA	Chemical	D016572
+12584269	838	843	FK506	Chemical	D016559
+12584269	876	879	SRL	Chemical	D020123
+12584269	1302	1310	fibrosis	Disease	D005355
+12584269	1324	1332	fibrosis	Disease	D005355
+12584269	1435	1443	fibrosis	Disease	D005355
+12584269	1492	1495	CsA	Chemical	D016572
+12584269	1497	1502	FK506	Chemical	D016559
+12584269	1507	1510	SRL	Chemical	D020123
+12584269	1586	1589	CsA	Chemical	D016572
+12584269	1615	1620	FK506	Chemical	D016559
+12584269	1624	1627	SRL	Chemical	D020123
+12584269	1690	1695	FK506	Chemical	D016559
+12584269	1701	1704	SRL	Chemical	D020123
+12584269	1904	1907	CsA	Chemical	D016572
+12584269	1913	1916	SRL	Chemical	D020123
+12584269	1989	1997	fibrosis	Disease	D005355
+12584269	2111	2116	FK506	Chemical	D016559
+12584269	2122	2125	SRL	Chemical	D020123
+12584269	2180	2188	fibrosis	Disease	D005355
+12584269	2279	2290	nephrotoxic	Disease	D007674
+12584269	2301	2304	CsA	Chemical	D016572
+12584269	2310	2313	SRL	Chemical	D020123
+12584269	2323	2328	FK506	Chemical	D016559
+12584269	2334	2337	SRL	Chemical	D020123
+12584269	CID	D016572	D007674
+12584269	CID	D016559	D007674
+12584269	CID	D020123	D007674
+
+10406016|t|Effect of fucoidan treatment on collagenase-induced intracerebral hemorrhage in rats.
+10406016|a|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.
+10406016	10	18	fucoidan	Chemical	C007789
+10406016	52	76	intracerebral hemorrhage	Disease	D002543
+10406016	143	155	brain damage	Disease	D001925
+10406016	166	181	ischemic stroke	Disease	D002544
+10406016	183	207	Intracerebral hemorrhage	Disease	D002543
+10406016	232	244	inflammation	Disease	D007249
+10406016	250	265	ischemic stroke	Disease	D002544
+10406016	305	313	fucoidan	Chemical	C007789
+10406016	362	374	brain damage	Disease	D001925
+10406016	394	418	intracerebral hemorrhage	Disease	D002543
+10406016	548	556	fucoidan	Chemical	C007789
+10406016	593	601	hematoma	Disease	D006406
+10406016	757	765	Fucoidan	Chemical	C007789
+10406016	801	824	impaired blood clotting	Disease	D020141
+10406016	829	841	hemodilution	Disease	D020141
+10406016	854	863	hematomas	Disease	D006406
+10406016	889	901	inflammation	Disease	D007249
+10406016	925	933	hematoma	Disease	D006406
+10406016	1047	1057	hemorrhage	Disease	D006470
+10406016	1123	1141	white matter edema	Disease	D001929
+10406016	1155	1168	neuronal loss	Disease	D009410
+10406016	1201	1209	hematoma	Disease	D006406
+10406016	1346	1370	intracerebral hemorrhage	Disease	D002543
+10406016	CID	C007789	D020141
+10406016	CID	C007789	D001929
+
+3403780|t|Paracetamol-associated coma, metabolic acidosis, renal and hepatic failure.
+3403780|a|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.
+3403780	0	11	Paracetamol	Chemical	D000082
+3403780	23	27	coma	Disease	D003128
+3403780	29	47	metabolic acidosis	Disease	D000138
+3403780	49	74	renal and hepatic failure	Disease	D058186|D017093	renal failure|hepatic failure
+3403780	86	104	metabolic acidosis	Disease	D000138
+3403780	106	145	acute renal failure and hepatic failure	Disease	D058186|D017114	acute renal failure|acute hepatic failure
+3403780	156	167	paracetamol	Chemical	D000082
+3403780	CID	D000082	D000138
+3403780	CID	D000082	D017114
+3403780	CID	D000082	D058186
+
+3101906|t|Hepatic reactions associated with ketoconazole in the United Kingdom.
+3101906|a|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.
+3101906	34	46	ketoconazole	Chemical	D007654
+3101906	70	82	Ketoconazole	Chemical	D007654
+3101906	219	233	hepatotoxicity	Disease	D056486
+3101906	275	281	deaths	Disease	D003643
+3101906	383	389	deaths	Disease	D003643
+3101906	621	635	hepatotoxicity	Disease	D056486
+3101906	718	726	jaundice	Disease	D007565
+3101906	878	899	hepatocellular injury	Disease	D056486
+3101906	1037	1048	cholestasis	Disease	D002779
+3101906	1157	1161	rash	Disease	D005076
+3101906	1166	1178	eosinophilia	Disease	D004802
+3101906	1190	1199	Hepatitis	Disease	D056486
+3101906	1364	1370	deaths	Disease	D003643
+3101906	1396	1408	ketoconazole	Chemical	D007654
+3101906	1466	1474	jaundice	Disease	D007565
+3101906	1497	1506	hepatitis	Disease	D056486
+3101906	1581	1590	hepatitis	Disease	D056486
+3101906	1634	1646	ketoconazole	Chemical	D007654
+3101906	1675	1689	hepatic injury	Disease	D056486
+3101906	CID	D007654	D007565
+3101906	CID	D007654	D002779
+3101906	CID	D007654	D056486
+
+9088814|t|Combined effects of prolonged prostaglandin E1-induced hypotension and haemodilution on human hepatic function.
+9088814|a|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.
+9088814	30	46	prostaglandin E1	Chemical	D000527
+9088814	55	66	hypotension	Disease	D007022
+9088814	71	84	haemodilution	Disease	D020141
+9088814	142	158	prostaglandin E1	Chemical	D000527
+9088814	160	164	PGE1	Chemical	D000527
+9088814	174	185	hypotension	Disease	D007022
+9088814	190	203	haemodilution	Disease	D020141
+9088814	392	403	hypotension	Disease	D007022
+9088814	440	453	haemodilution	Disease	D020141
+9088814	509	520	hypotension	Disease	D007022
+9088814	525	538	haemodilution	Disease	D020141
+9088814	540	553	Haemodilution	Disease	D020141
+9088814	672	679	dextran	Chemical	D003911
+9088814	746	757	hypotension	Disease	D007022
+9088814	793	797	PGE1	Chemical	D000527
+9088814	919	932	aceto-acetate	Chemical	C016635
+9088814	933	950	3-hydroxybutyrate	Chemical	D020155
+9088814	1206	1217	hypotension	Disease	D007022
+9088814	1301	1310	bilirubin	Chemical	D001663
+9088814	1430	1434	PGE1	Chemical	D000527
+9088814	1443	1454	hypotension	Disease	D007022
+9088814	1468	1481	haemodilution	Disease	D020141
+9088814	1494	1524	impairment of hepatic function	Disease	D008107
+9088814	CID	D000527	D007022
+9088814	CID	D000527	D008107
+
+20880751|t|Levodopa-induced dyskinesias in patients with Parkinson's disease: filling the bench-to-bedside gap.
+20880751|a|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.
+20880751	0	8	Levodopa	Chemical	D007980
+20880751	17	28	dyskinesias	Disease	D004409
+20880751	46	65	Parkinson's disease	Disease	D010300
+20880751	101	109	Levodopa	Chemical	D007980
+20880751	158	177	Parkinson's disease	Disease	D010300
+20880751	214	222	dopamine	Chemical	D004298
+20880751	285	296	dyskinesias	Disease	D004409
+20880751	436	444	levodopa	Chemical	D007980
+20880751	453	464	dyskinesias	Disease	D004409
+20880751	551	570	Parkinson's disease	Disease	D010300
+20880751	721	741	dyskinetic movements	Disease	D004409
+20880751	891	899	dopamine	Chemical	D004298
+20880751	947	956	glutamate	Chemical	D018698
+20880751	1040	1048	levodopa	Chemical	D007980
+20880751	1057	1068	dyskinesias	Disease	D004409
+20880751	CID	D007980	D004409
+
+20080419|t|Prevention of seizures and reorganization of hippocampal functions by transplantation of bone marrow cells in the acute phase of experimental epilepsy.
+20080419|a|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.
+20080419	14	22	seizures	Disease	D012640
+20080419	142	150	epilepsy	Disease	D004827
+20080419	263	271	epilepsy	Disease	D004827
+20080419	283	294	pilocarpine	Chemical	D010862
+20080419	430	448	status epilepticus	Disease	D013226
+20080419	450	452	SE	Disease	D013226
+20080419	455	485	Spontaneous recurrent seizures	Disease	-1
+20080419	487	490	SRS	Disease	-1
+20080419	522	529	seizure	Disease	D012640
+20080419	584	593	epileptic	Disease	D004827
+20080419	618	621	SRS	Disease	-1
+20080419	655	664	epileptic	Disease	D004827
+20080419	677	685	seizures	Disease	D012640
+20080419	858	867	epileptic	Disease	D004827
+20080419	880	888	seizures	Disease	D012640
+20080419	946	955	epileptic	Disease	D004827
+20080419	1197	1206	epileptic	Disease	D004827
+20080419	1296	1305	epileptic	Disease	D004827
+20080419	1386	1394	seizures	Disease	D012640
+20080419	1403	1416	neuronal loss	Disease	D009410
+20080419	CID	D010862	D004827
+20080419	CID	D010862	D013226
+
+19445921|t|Cardioprotective effect of salvianolic acid A on isoproterenol-induced myocardial infarction in rats.
+19445921|a|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.
+19445921	27	45	salvianolic acid A	Chemical	C066201
+19445921	49	62	isoproterenol	Chemical	D007545
+19445921	71	92	myocardial infarction	Disease	D009203
+19445921	179	197	salvianolic acid A	Chemical	C066201
+19445921	201	214	isoproterenol	Chemical	D007545
+19445921	223	244	myocardial infarction	Disease	D009203
+19445921	556	569	Isoproterenol	Chemical	D007545
+19445921	629	636	lactate	Chemical	D019344
+19445921	652	661	aspartate	Chemical	D001224
+19445921	676	684	creatine	Chemical	D003401
+19445921	696	711	malondialdehyde	Chemical	D008315
+19445921	759	769	superoxide	Chemical	D013481
+19445921	794	805	glutathione	Chemical	D005978
+19445921	1073	1096	respiratory dysfunction	Disease	D012131
+19445921	1154	1157	ADP	Chemical	D000244
+19445921	1176	1189	isoproterenol	Chemical	D007545
+19445921	1222	1240	salvianolic acid A	Chemical	C066201
+19445921	1289	1302	isoproterenol	Chemical	D007545
+19445921	1311	1330	cardiac dysfunction	Disease	D006331
+19445921	1335	1352	myocardial injury	Disease	D009202
+19445921	1425	1443	salvianolic acid A	Chemical	C066201
+19445921	1452	1465	isoproterenol	Chemical	D007545
+19445921	1474	1491	myocardial damage	Disease	D009202
+19445921	1586	1604	salvianolic acid A	Chemical	C066201
+19445921	1681	1694	isoproterenol	Chemical	D007545
+19445921	1703	1724	myocardial infarction	Disease	D009203
+19445921	CID	D007545	D009203
+
+18439803|t|Acute effects of N-(2-propylpentanoyl)urea on hippocampal amino acid neurotransmitters in pilocarpine-induced seizure in rats.
+18439803|a|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.
+18439803	17	42	N-(2-propylpentanoyl)urea	Chemical	C108761
+18439803	58	68	amino acid	Chemical	D000596
+18439803	90	101	pilocarpine	Chemical	D010862
+18439803	110	117	seizure	Disease	D012640
+18439803	245	255	amino acid	Chemical	D000596
+18439803	275	284	glutamate	Chemical	D018698
+18439803	286	295	aspartate	Chemical	D001224
+18439803	297	304	glycine	Chemical	D005998
+18439803	309	313	GABA	Chemical	D005680
+18439803	318	343	N-(2-propylpentanoyl)urea	Chemical	C108761
+18439803	345	348	VPU	Chemical	C108761
+18439803	388	401	valproic acid	Chemical	D014635
+18439803	403	406	VPA	Chemical	D014635
+18439803	409	412	VPU	Chemical	C108761
+18439803	434	437	VPA	Chemical	D014635
+18439803	524	535	pilocarpine	Chemical	D010862
+18439803	544	551	seizure	Disease	D012640
+18439803	588	591	VPA	Chemical	D014635
+18439803	684	695	pilocarpine	Chemical	D010862
+18439803	742	751	glutamate	Chemical	D018698
+18439803	756	765	aspartate	Chemical	D001224
+18439803	825	832	glycine	Chemical	D005998
+18439803	837	841	GABA	Chemical	D005680
+18439803	868	871	VPU	Chemical	C108761
+18439803	894	897	VPA	Chemical	D014635
+18439803	939	950	pilocarpine	Chemical	D010862
+18439803	985	994	glutamate	Chemical	D018698
+18439803	999	1008	aspartate	Chemical	D001224
+18439803	1095	1099	GABA	Chemical	D005680
+18439803	1104	1111	glycine	Chemical	D005998
+18439803	1149	1158	glutamate	Chemical	D018698
+18439803	1163	1172	aspartate	Chemical	D001224
+18439803	1206	1209	VPU	Chemical	C108761
+18439803	1214	1217	VPA	Chemical	D014635
+18439803	1252	1263	pilocarpine	Chemical	D010862
+18439803	1272	1279	seizure	Disease	D012640
+18439803	1329	1339	amino acid	Chemical	D000596
+18439803	1422	1431	glutamate	Chemical	D018698
+18439803	1436	1445	aspartate	Chemical	D001224
+18439803	1463	1466	VPA	Chemical	D014635
+18439803	1485	1488	VPU	Chemical	C108761
+18439803	1514	1525	pilocarpine	Chemical	D010862
+18439803	1547	1556	glutamate	Chemical	D018698
+18439803	1561	1570	aspartate	Chemical	D001224
+18439803	1648	1659	pilocarpine	Chemical	D010862
+18439803	1668	1675	seizure	Disease	D012640
+18439803	CID	D010862	D012640
+
+17919553|t|Acute hepatitis attack after exposure to telithromycin.
+17919553|a|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.
+17919553	6	15	hepatitis	Disease	D056486
+17919553	41	54	telithromycin	Chemical	C106791
+17919553	92	106	hepatotoxicity	Disease	D056486
+17919553	170	184	hepatic injury	Disease	D056486
+17919553	214	236	adverse drug reactions	Disease	D064420
+17919553	475	483	jaundice	Disease	D007565
+17919553	494	500	nausea	Disease	D009325
+17919553	506	514	vomiting	Disease	D014839
+17919553	539	552	telithromycin	Chemical	C106791
+17919553	577	610	upper respiratory tract infection	Disease	D012141
+17919553	669	676	alanine	Chemical	D000409
+17919553	732	741	aspartate	Chemical	D001224
+17919553	904	913	bilirubin	Chemical	D001663
+17919553	950	959	bilirubin	Chemical	D001663
+17919553	1037	1044	alcohol	Chemical	D000431
+17919553	1130	1139	hepatitis	Disease	D056486
+17919553	1180	1193	telithromycin	Chemical	C106791
+17919553	1252	1265	Telithromycin	Chemical	C106791
+17919553	1449	1468	hepatic dysfunction	Disease	D008107
+17919553	1507	1528	adverse drug reaction	Disease	D064420
+17919553	1548	1561	telithromycin	Chemical	C106791
+17919553	1594	1603	hepatitis	Disease	D056486
+17919553	1670	1685	toxic hepatitis	Disease	D056486
+17919553	1701	1710	hepatitis	Disease	D056486
+17919553	1830	1843	telithromycin	Chemical	C106791
+17919553	1904	1913	hepatitis	Disease	D056486
+17919553	1961	1974	telithromycin	Chemical	C106791
+17919553	CID	C106791	D056486
+
+15632880|t|Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure.
+15632880|a|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.
+15632880	0	14	Spironolactone	Chemical	D013148
+15632880	23	42	renal insufficiency	Disease	D051437
+15632880	47	59	hyperkalemia	Disease	D006947
+15632880	77	90	heart failure	Disease	D006333
+15632880	165	179	spironolactone	Chemical	D013148
+15632880	183	196	heart failure	Disease	D006333
+15632880	229	241	hyperkalemia	Disease	D006947
+15632880	251	270	renal insufficiency	Disease	D051437
+15632880	300	313	heart failure	Disease	D006333
+15632880	349	363	spironolactone	Chemical	D013148
+15632880	535	547	hyperkalemia	Disease	D006947
+15632880	552	571	renal insufficiency	Disease	D051437
+15632880	575	588	heart failure	Disease	D006333
+15632880	611	625	spironolactone	Chemical	D013148
+15632880	673	686	heart failure	Disease	D006333
+15632880	709	723	spironolactone	Chemical	D013148
+15632880	784	796	hyperkalemia	Disease	D006947
+15632880	798	799	K	Chemical	D011188
+15632880	818	837	renal insufficiency	Disease	D051437
+15632880	839	841	Cr	Chemical	D002857
+15632880	1110	1124	spironolactone	Chemical	D013148
+15632880	1132	1144	hyperkalemia	Disease	D006947
+15632880	1157	1170	renal failure	Disease	D051437
+15632880	1204	1216	hyperkalemia	Disease	D006947
+15632880	1252	1260	diabetes	Disease	D003920
+15632880	1288	1297	potassium	Chemical	D011188
+15632880	1324	1333	potassium	Chemical	D011188
+15632880	1454	1473	renal insufficiency	Disease	D051437
+15632880	1531	1541	creatinine	Chemical	D003404
+15632880	1624	1632	thiazide	Chemical	D049971
+15632880	1671	1685	Spironolactone	Chemical	D013148
+15632880	1694	1706	hyperkalemia	Disease	D006947
+15632880	1711	1730	renal insufficiency	Disease	D051437
+15632880	CID	D013148	D006947
+15632880	CID	D013148	D051437
+
+11773892|t|End-stage renal disease (ESRD) after orthotopic liver transplantation (OLTX) using calcineurin-based immunotherapy: risk of development and treatment.
+11773892|a|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.
+11773892	0	23	End-stage renal disease	Disease	D007676
+11773892	25	29	ESRD	Disease	D007676
+11773892	190	202	cyclosporine	Chemical	D016572
+11773892	207	217	tacrolimus	Chemical	D016559
+11773892	239	250	nephrotoxic	Disease	D007674
+11773892	436	459	end-stage renal disease	Disease	D007676
+11773892	461	465	ESRD	Disease	D007676
+11773892	533	537	ESRD	Disease	D007676
+11773892	542	563	chronic renal failure	Disease	D007676
+11773892	565	568	CRF	Disease	D007676
+11773892	851	854	CRF	Disease	D007676
+11773892	858	862	ESRD	Disease	D007676
+11773892	871	874	CRF	Disease	D007676
+11773892	892	902	creatinine	Chemical	D003404
+11773892	925	929	ESRD	Disease	D007676
+11773892	1051	1055	ESRD	Disease	D007676
+11773892	1092	1096	ESRD	Disease	D007676
+11773892	1155	1172	renal dysfunction	Disease	D007674
+11773892	1184	1187	CRF	Disease	D007676
+11773892	1197	1201	ESRD	Disease	D007676
+11773892	1241	1244	CRF	Disease	D007676
+11773892	1249	1253	ESRD	Disease	D007676
+11773892	1293	1303	creatinine	Chemical	D003404
+11773892	1350	1370	hepatorenal syndrome	Disease	D006530
+11773892	1480	1490	creatinine	Chemical	D003404
+11773892	1627	1637	creatinine	Chemical	D003404
+11773892	1762	1765	CRF	Disease	D007676
+11773892	1769	1773	ESRD	Disease	D007676
+11773892	1965	1969	ESRD	Disease	D007676
+11773892	2047	2051	ESRD	Disease	D007676
+11773892	2089	2093	ESRD	Disease	D007676
+11773892	2182	2186	ESRD	Disease	D007676
+11773892	2297	2300	CRF	Disease	D007676
+11773892	2305	2309	ESRD	Disease	D007676
+11773892	2345	2349	ESRD	Disease	D007676
+11773892	2450	2454	ESRD	Disease	D007676
+11773892	2499	2509	creatinine	Chemical	D003404
+11773892	2538	2558	hepatorenal syndrome	Disease	D006530
+11773892	2590	2600	creatinine	Chemical	D003404
+11773892	2675	2678	CRF	Disease	D007676
+11773892	2682	2686	ESRD	Disease	D007676
+11773892	CID	D016559	D007674
+11773892	CID	D016572	D007674
+
+10835440|t|Effect of intravenous nimodipine on blood pressure and outcome after acute stroke.
+10835440|a|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.
+10835440	22	32	nimodipine	Chemical	D009553
+10835440	69	81	acute stroke	Disease	D020521
+10835440	123	133	Nimodipine	Chemical	D009553
+10835440	148	154	Stroke	Disease	D020521
+10835440	198	208	nimodipine	Chemical	D009553
+10835440	217	244	reduction in blood pressure	Disease	D007022
+10835440	280	292	acute stroke	Disease	D020521
+10835440	451	463	BP reduction	Disease	D007022
+10835440	512	527	ischemic stroke	Disease	D002544
+10835440	621	631	nimodipine	Chemical	D009553
+10835440	663	673	nimodipine	Chemical	D009553
+10835440	931	941	Nimodipine	Chemical	D009553
+10835440	992	1016	reduction in systolic BP	Disease	D007022
+10835440	1169	1182	DBP reduction	Disease	D007022
+10835440	1296	1309	DBP reduction	Disease	D007022
+10835440	1422	1427	death	Disease	D003643
+10835440	1512	1517	death	Disease	D003643
+10835440	1829	1839	nimodipine	Chemical	D009553
+10835440	1846	1858	acute stroke	Disease	D020521
+10835440	1873	1883	nimodipine	Chemical	D009553
+10835440	1988	1998	nimodipine	Chemical	D009553
+10835440	CID	D009553	D007022
+
+9523805|t|Transient neurologic symptoms after spinal anesthesia: a lower incidence with prilocaine and bupivacaine than with lidocaine.
+9523805|a|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.
+9523805	0	29	Transient neurologic symptoms	Disease	D009422
+9523805	78	88	prilocaine	Chemical	D011318
+9523805	93	104	bupivacaine	Chemical	D002045
+9523805	115	124	lidocaine	Chemical	D008012
+9523805	168	197	transient neurologic symptoms	Disease	D009422
+9523805	199	203	TNSs	Disease	D009422
+9523805	223	232	lidocaine	Chemical	D008012
+9523805	275	286	bupivacaine	Chemical	D002045
+9523805	365	374	lidocaine	Chemical	D008012
+9523805	432	442	Prilocaine	Chemical	D011318
+9523805	517	526	lidocaine	Chemical	D008012
+9523805	594	604	prilocaine	Chemical	D011318
+9523805	610	619	lidocaine	Chemical	D008012
+9523805	624	635	bupivacaine	Chemical	D002045
+9523805	692	696	TNSs	Disease	D009422
+9523805	920	929	lidocaine	Chemical	D008012
+9523805	938	945	glucose	Chemical	D005947
+9523805	950	960	prilocaine	Chemical	D011318
+9523805	969	976	glucose	Chemical	D005947
+9523805	986	997	bupivacaine	Chemical	D002045
+9523805	1006	1013	glucose	Chemical	D005947
+9523805	1277	1281	TNSs	Disease	D009422
+9523805	1414	1423	lidocaine	Chemical	D008012
+9523805	1436	1440	TNSs	Disease	D009422
+9523805	1469	1479	prilocaine	Chemical	D011318
+9523805	1535	1546	bupivacaine	Chemical	D002045
+9523805	1551	1555	TNSs	Disease	D009422
+9523805	1606	1615	lidocaine	Chemical	D008012
+9523805	1620	1630	prilocaine	Chemical	D011318
+9523805	1703	1714	bupivacaine	Chemical	D002045
+9523805	1771	1781	Prilocaine	Chemical	D011318
+9523805	1803	1812	lidocaine	Chemical	D008012
+9523805	1912	1916	TNSs	Disease	D009422
+9523805	CID	D008012	D009422
+9523805	CID	D011318	D009422
+
+9245658|t|The role of nicotine in smoking-related cardiovascular disease.
+9245658|a|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.
+9245658	12	20	nicotine	Chemical	D009538
+9245658	40	62	cardiovascular disease	Disease	D002318
+9245658	64	72	Nicotine	Chemical	D009538
+9245658	150	172	cardiovascular disease	Disease	D002318
+9245658	227	235	nicotine	Chemical	D009538
+9245658	270	285	atherosclerosis	Disease	D050197
+9245658	388	396	nicotine	Chemical	D009538
+9245658	524	532	nicotine	Chemical	D009538
+9245658	631	646	carbon monoxide	Chemical	D002248
+9245658	648	656	Nicotine	Chemical	D009538
+9245658	684	694	thrombosis	Disease	D013927
+9245658	771	779	nicotine	Chemical	D009538
+9245658	820	828	nicotine	Chemical	D009538
+9245658	947	955	nicotine	Chemical	D009538
+9245658	995	1003	nicotine	Chemical	D009538
+9245658	CID	D009538	D002318
+9245658	CID	D009538	D050197
+
+9034419|t|Seizure resulting from a venlafaxine overdose.
+9034419|a|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.
+9034419	0	7	Seizure	Disease	D012640
+9034419	25	36	venlafaxine	Chemical	C047426
+9034419	37	45	overdose	Disease	D062787
+9034419	78	89	venlafaxine	Chemical	C047426
+9034419	90	98	overdose	Disease	D062787
+9034419	139	155	major depression	Disease	D003865
+9034419	164	172	overdose	Disease	D062787
+9034419	176	187	venlafaxine	Chemical	C047426
+9034419	246	257	venlafaxine	Chemical	C047426
+9034419	321	328	seizure	Disease	D012640
+9034419	383	394	venlafaxine	Chemical	C047426
+9034419	513	524	venlafaxine	Chemical	C047426
+9034419	525	533	overdose	Disease	D062787
+9034419	565	572	seizure	Disease	D012640
+9034419	636	647	venlafaxine	Chemical	C047426
+9034419	753	764	venlafaxine	Chemical	C047426
+9034419	765	773	overdose	Disease	D062787
+9034419	833	840	seizure	Disease	D012640
+9034419	CID	C047426	D012640
+9034419	CID	C047426	D062787
+
+8829025|t|Effect of nifedipine on renal function in liver transplant recipients receiving tacrolimus.
+8829025|a|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.
+8829025	10	20	nifedipine	Chemical	D009543
+8829025	80	90	tacrolimus	Chemical	D016559
+8829025	106	116	nifedipine	Chemical	D009543
+8829025	185	195	tacrolimus	Chemical	D016559
+8829025	282	292	tacrolimus	Chemical	D016559
+8829025	353	365	hypertensive	Disease	D006973
+8829025	394	404	nifedipine	Chemical	D009543
+8829025	470	480	nifedipine	Chemical	D009543
+8829025	548	558	Nifedipine	Chemical	D009543
+8829025	646	656	creatinine	Chemical	D003404
+8829025	716	726	nifedipine	Chemical	D009543
+8829025	743	757	nephrotoxicity	Disease	D007674
+8829025	774	784	tacrolimus	Chemical	D016559
+8829025	877	889	hypertension	Disease	D006973
+8829025	CID	D016559	D006973
+
+8437969|t|Sinus arrest associated with continuous-infusion cimetidine.
+8437969|a|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.
+8437969	0	12	Sinus arrest	Disease	D054138
+8437969	49	59	cimetidine	Chemical	D002927
+8437969	121	131	cimetidine	Chemical	D002927
+8437969	183	199	bradyarrhythmias	Disease	D001919
+8437969	224	232	leukemia	Disease	D007938
+8437969	251	266	cardiac disease	Disease	D006331
+8437969	315	327	sinus arrest	Disease	D054138
+8437969	364	374	cimetidine	Chemical	D002927
+8437969	391	402	arrhythmias	Disease	D001145
+8437969	430	440	cimetidine	Chemical	D002927
+8437969	513	523	ranitidine	Chemical	D011899
+8437969	570	582	sinus arrest	Disease	D054138
+8437969	619	629	cimetidine	Chemical	D002927
+8437969	CID	D002927	D054138
+8437969	CID	D002927	D001919
+
+7890216|t|Composition of gall bladder stones associated with octreotide: response to oral ursodeoxycholic acid.
+7890216|a|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.
+7890216	15	34	gall bladder stones	Disease	D042882
+7890216	51	61	octreotide	Chemical	D015282
+7890216	80	100	ursodeoxycholic acid	Chemical	D014580
+7890216	102	112	Octreotide	Chemical	D015282
+7890216	141	151	acromegaly	Disease	D000172
+7890216	161	180	gall bladder stones	Disease	D042882
+7890216	377	387	octreotide	Chemical	D015282
+7890216	396	407	acromegalic	Disease	D000172
+7890216	422	433	gall stones	Disease	D042882
+7890216	456	467	gall stones	Disease	D042882
+7890216	555	566	cholesterol	Chemical	D002784
+7890216	773	784	cholesterol	Chemical	D002784
+7890216	958	969	cholesterol	Chemical	D002784
+7890216	1050	1061	cholesterol	Chemical	D002784
+7890216	1151	1162	cholesterol	Chemical	D002784
+7890216	1244	1264	ursodeoxycholic acid	Chemical	D014580
+7890216	1266	1270	UDCA	Chemical	D014580
+7890216	1337	1341	UDCA	Chemical	D014580
+7890216	1490	1500	gall stone	Disease	D042882
+7890216	1548	1559	cholesterol	Chemical	D002784
+7890216	1634	1644	gall stone	Disease	D042882
+7890216	1694	1704	octreotide	Chemical	D015282
+7890216	1713	1724	gall stones	Disease	D042882
+7890216	1760	1771	cholesterol	Chemical	D002784
+7890216	1814	1832	gall stone disease	Disease	D042882
+7890216	1905	1916	gall stones	Disease	D042882
+7890216	1928	1935	calcium	Chemical	D002118
+7890216	CID	D015282	D042882
+
+7468724|t|Cardiovascular complications associated with terbutaline treatment for preterm labor.
+7468724|a|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.
+7468724	0	28	Cardiovascular complications	Disease	D002318
+7468724	45	56	terbutaline	Chemical	D013726
+7468724	71	84	preterm labor	Disease	D007752
+7468724	93	121	cardiovascular complications	Disease	D002318
+7468724	169	180	terbutaline	Chemical	D013726
+7468724	185	198	preterm labor	Disease	D007752
+7468724	CID	D013726	D002318
+
+7199841|t|Neurologic effects of subarachnoid administration of 2-chloroprocaine-CE, bupivacaine, and low pH normal saline in dogs.
+7199841|a|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.
+7199841	53	72	2-chloroprocaine-CE	Chemical	C004616
+7199841	74	85	bupivacaine	Chemical	D002045
+7199841	248	267	2-chloroprocaine-CE	Chemical	C004616
+7199841	377	390	neurotoxicity	Disease	D020258
+7199841	502	513	bupivacaine	Chemical	D002045
+7199841	524	543	2-chloroprocaine-CE	Chemical	C004616
+7199841	679	698	2-chloroprocaine-CE	Chemical	C004616
+7199841	731	740	paralysis	Disease	D010243
+7199841	776	787	bupivacaine	Chemical	D002045
+7199841	862	871	paralysis	Disease	D010243
+7199841	925	944	2-chloroprocaine-CE	Chemical	C004616
+7199841	956	972	subpial necrosis	Disease	D013118
+7199841	1074	1085	bupivacaine	Chemical	D002045
+7199841	CID	C004616	D010243
+7199841	CID	C004616	D013118
+
+6640832|t|Early adjuvant adriamycin in superficial bladder carcinoma.
+6640832|a|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.
+6640832	15	25	adriamycin	Chemical	D004317
+6640832	41	58	bladder carcinoma	Disease	D001749|D002277	bladder carcinoma|carcinoma
+6640832	145	169	carcinoma of the bladder	Disease	D001749|D002277	carcinoma of the bladder|carcinoma
+6640832	171	181	Adriamycin	Chemical	D004317
+6640832	285	299	bladder tumors	Disease	D001749
+6640832	561	569	cystitis	Disease	D003556
+6640832	1048	1054	tumors	Disease	D009369
+6640832	1187	1192	tumor	Disease	D009369
+6640832	1419	1429	Adriamycin	Chemical	D004317
+6640832	CID	D004317	D003556
+
+3560096|t|Hyperkalemia associated with sulindac therapy.
+3560096|a|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.
+3560096	0	12	Hyperkalemia	Disease	D006947
+3560096	29	37	sulindac	Chemical	D013467
+3560096	47	59	Hyperkalemia	Disease	D006947
+3560096	163	175	indomethacin	Chemical	D007213
+3560096	244	252	sulindac	Chemical	D013467
+3560096	299	311	prostacyclin	Chemical	D011464
+3560096	354	366	hyperkalemia	Disease	D006947
+3560096	429	437	sulindac	Chemical	D013467
+3560096	482	491	potassium	Chemical	D011188
+3560096	538	546	sulindac	Chemical	D013467
+3560096	594	603	potassium	Chemical	D011188
+3560096	713	721	sulindac	Chemical	D013467
+3560096	726	738	hyperkalemia	Disease	D006947
+3560096	792	800	sulindac	Chemical	D013467
+3560096	CID	D007213	D006947
+3560096	CID	D013467	D006947
+
+3358181|t|Ventricular tachyarrhythmias during cesarean section after ritodrine therapy: interaction with anesthetics.
+3358181|a|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.
+3358181	0	28	Ventricular tachyarrhythmias	Disease	D014693
+3358181	59	68	ritodrine	Chemical	D012312
+3358181	154	163	ritodrine	Chemical	D012312
+3358181	168	181	preterm labor	Disease	D007752
+3358181	248	257	ritodrine	Chemical	D012312
+3358181	354	382	cardiovascular complications	Disease	D002318
+3358181	422	431	ritodrine	Chemical	D012312
+3358181	505	514	potassium	Chemical	D011188
+3358181	662	671	ephedrine	Chemical	D004809
+3358181	805	818	phenylephrine	Chemical	D010656
+3358181	828	839	hypotensive	Disease	D007022
+3358181	854	865	tachycardia	Disease	D013610
+3358181	CID	D012312	D014693
+
+2887062|t|Immunohistochemical, electron microscopic and morphometric studies of estrogen-induced rat prolactinomas after bromocriptine treatment.
+2887062|a|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.
+2887062	70	78	estrogen	Chemical	D004967
+2887062	91	104	prolactinomas	Disease	D015175
+2887062	111	124	bromocriptine	Chemical	D001971
+2887062	162	175	bromocriptine	Chemical	D001971
+2887062	179	191	prolactinoma	Disease	D015175
+2887062	288	296	estrogen	Chemical	D004967
+2887062	309	321	prolactinoma	Disease	D015175
+2887062	359	372	bromocriptine	Chemical	D001971
+2887062	613	625	prolactinoma	Disease	D015175
+2887062	866	879	bromocriptine	Chemical	D001971
+2887062	1095	1107	prolactinoma	Disease	D015175
+2887062	1409	1421	prolactinoma	Disease	D015175
+2887062	1524	1537	bromocriptine	Chemical	D001971
+2887062	1555	1562	adenoma	Disease	D000236
+2887062	1770	1783	bromocriptine	Chemical	D001971
+2887062	CID	D004967	D015175
+
+2425813|t|On two paradoxical side-effects of prednisolone in rats, ribosomal RNA biosyntheses, and a mechanism of action.
+2425813|a|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.
+2425813	35	47	prednisolone	Chemical	D011239
+2425813	112	129	Liver enlargement	Disease	D006529
+2425813	134	148	muscle wastage	Disease	D009133
+2425813	218	230	prednisolone	Chemical	D011239
+2425813	670	682	prednisolone	Chemical	D011239
+2425813	CID	D011239	D006529
+2425813	CID	D011239	D009133
+
+2375138|t|Possible intramuscular midazolam-associated cardiorespiratory arrest and death.
+2375138|a|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.
+2375138	23	32	midazolam	Chemical	D008874
+2375138	44	68	cardiorespiratory arrest	Disease	D006323
+2375138	73	78	death	Disease	D003643
+2375138	80	103	Midazolam hydrochloride	Chemical	D008874
+2375138	265	306	respiratory and cardiovascular depression	Disease	D012140|D002318	respiratory depression|cardiovascular depression
+2375138	358	382	cardiorespiratory arrest	Disease	D006323
+2375138	387	392	death	Disease	D003643
+2375138	441	450	midazolam	Chemical	D008874
+2375138	474	483	midazolam	Chemical	D008874
+2375138	CID	D008874	D012140
+2375138	CID	D008874	D006323
+
+2265898|t|Serial epilepsy caused by levodopa/carbidopa administration in two patients on hemodialysis.
+2265898|a|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.
+2265898	7	15	epilepsy	Disease	D004827
+2265898	26	44	levodopa/carbidopa	Chemical	C009265
+2265898	170	191	chronic renal failure	Disease	D007676
+2265898	294	312	carbidopa/levodopa	Chemical	C009265
+2265898	352	364	hallucinosis	Disease	D001523
+2265898	379	387	seizures	Disease	D012640
+2265898	550	560	vitamin B6	Chemical	D025101
+2265898	CID	C009265	D004827
+
+2071257|t|Effect of L-alpha-glyceryl-phosphorylcholine on amnesia caused by scopolamine.
+2071257|a|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.
+2071257	10	44	L-alpha-glyceryl-phosphorylcholine	Chemical	D005997
+2071257	48	55	amnesia	Disease	D000647
+2071257	66	77	scopolamine	Chemical	D012601
+2071257	136	169	L-alpha-glycerylphosphorylcholine	Chemical	D005997
+2071257	171	182	L-alpha-GFC	Chemical	D005997
+2071257	187	204	memory impairment	Disease	D008569
+2071257	216	227	scopolamine	Chemical	D012601
+2071257	373	384	L-alpha-GFC	Chemical	D005997
+2071257	434	445	scopolamine	Chemical	D012601
+2071257	638	672	impairment of attention and memory	Disease	D008569
+2071257	684	695	scopolamine	Chemical	D012601
+2071257	CID	D012601	D008569
+
+1592014|t|Seizures induced by the cocaine metabolite benzoylecgonine in rats.
+1592014|a|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.
+1592014	0	8	Seizures	Disease	D012640
+1592014	24	31	cocaine	Chemical	D003042
+1592014	43	58	benzoylecgonine	Chemical	C005618
+1592014	92	99	cocaine	Chemical	D003042
+1592014	170	178	seizures	Disease	D012640
+1592014	183	190	strokes	Disease	D020521
+1592014	272	279	cocaine	Chemical	D003042
+1592014	389	396	cocaine	Chemical	D003042
+1592014	398	413	benzoylecgonine	Chemical	C005618
+1592014	415	417	BE	Chemical	C005618
+1592014	429	437	seizures	Disease	D012640
+1592014	498	505	cocaine	Chemical	D003042
+1592014	509	511	BE	Chemical	C005618
+1592014	634	641	seizure	Disease	D012640
+1592014	695	703	seizures	Disease	D012640
+1592014	705	707	BE	Chemical	C005618
+1592014	716	724	seizures	Disease	D012640
+1592014	832	839	cocaine	Chemical	D003042
+1592014	849	856	cocaine	Chemical	D003042
+1592014	865	873	seizures	Disease	D012640
+1592014	947	952	death	Disease	D003643
+1592014	971	973	BE	Chemical	C005618
+1592014	1047	1052	death	Disease	D003643
+1592014	1170	1177	seizure	Disease	D012640
+1592014	1190	1192	BE	Chemical	C005618
+1592014	1225	1233	seizures	Disease	D012640
+1592014	1281	1288	cocaine	Chemical	D003042
+1592014	1314	1322	seizures	Disease	D012640
+1592014	1341	1348	cocaine	Chemical	D003042
+1592014	1354	1356	BE	Chemical	C005618
+1592014	1365	1373	seizures	Disease	D012640
+1592014	1438	1445	cocaine	Chemical	D003042
+1592014	1454	1462	seizures	Disease	D012640
+1592014	1498	1505	cocaine	Chemical	D003042
+1592014	1518	1520	BE	Chemical	C005618
+1592014	CID	D003042	D012640
+1592014	CID	C005618	D012640
+
+1436384|t|Protection against amphetamine-induced neurotoxicity toward striatal dopamine neurons in rodents by LY274614, an excitatory amino acid antagonist.
+1436384|a|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.
+1436384	19	30	amphetamine	Chemical	D000661
+1436384	39	52	neurotoxicity	Disease	D020258
+1436384	69	77	dopamine	Chemical	D004298
+1436384	100	108	LY274614	Chemical	C070935
+1436384	124	134	amino acid	Chemical	D000596
+1436384	147	155	LY274614	Chemical	C070935
+1436384	157	235	3SR,4aRS,6SR,8aRS-6-[phosphonomethyl]decahydr oisoquinoline-3- carboxylic acid	Chemical	C070935
+1436384	286	306	N-methyl-D-aspartate	Chemical	D016202
+1436384	308	312	NMDA	Chemical	D016202
+1436384	325	334	glutamate	Chemical	D018698
+1436384	403	411	dopamine	Chemical	D004298
+1436384	431	442	amphetamine	Chemical	D000661
+1436384	446	455	iprindole	Chemical	D007488
+1436384	523	534	amphetamine	Chemical	D000661
+1436384	578	587	iprindole	Chemical	D007488
+1436384	625	633	dopamine	Chemical	D004298
+1436384	692	700	dopamine	Chemical	D004298
+1436384	736	747	dizocilpine	Chemical	D016291
+1436384	749	755	MK-801	Chemical	D016291
+1436384	789	793	NMDA	Chemical	D016202
+1436384	811	819	LY274614	Chemical	C070935
+1436384	849	853	NMDA	Chemical	D016202
+1436384	891	899	LY274614	Chemical	C070935
+1436384	975	983	LY274614	Chemical	C070935
+1436384	1031	1039	dopamine	Chemical	D004298
+1436384	1093	1104	amphetamine	Chemical	D000661
+1436384	1139	1150	amphetamine	Chemical	D000661
+1436384	1165	1173	dopamine	Chemical	D004298
+1436384	1216	1224	LY274614	Chemical	C070935
+1436384	1258	1269	amphetamine	Chemical	D000661
+1436384	1271	1279	LY274614	Chemical	C070935
+1436384	1354	1365	amphetamine	Chemical	D000661
+1436384	1394	1402	dopamine	Chemical	D004298
+1436384	1457	1472	methamphetamine	Chemical	D008694
+1436384	1530	1538	LY274614	Chemical	C070935
+1436384	1582	1592	neurotoxic	Disease	D020258
+1436384	1603	1614	amphetamine	Chemical	D000661
+1436384	1658	1666	dopamine	Chemical	D004298
+1436384	1684	1688	NMDA	Chemical	D016202
+1436384	1708	1716	LY274614	Chemical	C070935
+1436384	1723	1727	NMDA	Chemical	D016202
+1436384	CID	D000661	D020258
+
+1085609|t|Neonatal pyridoxine responsive convulsions due to isoniazid therapy.
+1085609|a|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.
+1085609	9	19	pyridoxine	Chemical	D011736
+1085609	31	42	convulsions	Disease	D012640
+1085609	50	59	isoniazid	Chemical	D007538
+1085609	92	101	isoniazid	Chemical	D007538
+1085609	156	168	tuberculosis	Disease	D014376
+1085609	198	209	clonic fits	Disease	D012640
+1085609	276	280	fits	Disease	D012640
+1085609	334	344	pyridoxine	Chemical	D011736
+1085609	373	383	pyridoxine	Chemical	D011736
+1085609	408	417	isoniazid	Chemical	D007538
+1085609	CID	D007538	D012640
+
+809711|t|Reversal by phenylephrine of the beneficial effects of intravenous nitroglycerin in patients with acute myocardial infarction.
+809711|a|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.
+809711	12	25	phenylephrine	Chemical	D010656
+809711	67	80	nitroglycerin	Chemical	D005996
+809711	98	125	acute myocardial infarction	Disease	D009203
+809711	127	140	Nitroglycerin	Chemical	D005996
+809711	194	221	acute myocardial infarction	Disease	D009203
+809711	279	292	nitroglycerin	Chemical	D005996
+809711	301	312	hypotension	Disease	D007022
+809711	374	387	nitroglycerin	Chemical	D005996
+809711	392	405	phenylephrine	Chemical	D010656
+809711	450	472	myocardial infarctions	Disease	D009203
+809711	494	507	nitroglycerin	Chemical	D005996
+809711	832	845	nitroglycerin	Chemical	D005996
+809711	870	883	phenylephrine	Chemical	D010656
+809711	1176	1189	phenylephrine	Chemical	D010656
+809711	1193	1206	nitroglycerin	Chemical	D005996
+809711	1259	1286	acute myocardial infarction	Disease	D009203
+809711	CID	D005996	D007022
+
+20621845|t|Elevation of ADAM10, ADAM17, MMP-2 and MMP-9 expression with media degeneration features CaCl2-induced thoracic aortic aneurysm in a rat model.
+20621845|a|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.
+20621845	89	94	CaCl2	Chemical	D002122
+20621845	103	127	thoracic aortic aneurysm	Disease	D017545
+20621845	205	229	thoracic aortic aneurysm	Disease	D017545
+20621845	231	234	TAA	Disease	D017545
+20621845	239	255	calcium chloride	Chemical	D002122
+20621845	257	264	CaCl(2)	Chemical	D002122
+20621845	274	289	arterial injury	Disease	D014652
+20621845	447	450	TAA	Disease	D017545
+20621845	534	541	CaCl(2)	Chemical	D002122
+20621845	560	564	NaCl	Chemical	D012965
+20621845	611	618	CaCl(2)	Chemical	D002122
+20621845	628	635	CaCl(2)	Chemical	D002122
+20621845	657	661	NaCl	Chemical	D012965
+20621845	925	932	CaCl(2)	Chemical	D002122
+20621845	946	953	CaCl(2)	Chemical	D002122
+20621845	966	970	NaCl	Chemical	D012965
+20621845	1167	1174	CaCl(2)	Chemical	D002122
+20621845	1257	1264	CaCl(2)	Chemical	D002122
+20621845	1324	1331	CaCl(2)	Chemical	D002122
+20621845	1369	1373	NaCl	Chemical	D012965
+20621845	1533	1540	CaCl(2)	Chemical	D002122
+20621845	1682	1685	TAA	Disease	D017545
+20621845	1708	1715	CaCl(2)	Chemical	D002122
+20621845	CID	D002122	D017545
+
+19843802|t|When drugs disappear from the patient: elimination of intravenous medication by hemodiafiltration.
+19843802|a|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.
+19843802	170	189	right heart failure	Disease	D006333
+19843802	297	311	catecholamines	Chemical	D002395
+19843802	430	441	epinephrine	Chemical	D004837
+19843802	494	506	hypertensive	Disease	D006973
+19843802	672	685	catecholamine	Chemical	D002395
+19843802	CID	D004837	D006973
+
+19473225|t|Long-term glutamate supplementation failed to protect against peripheral neurotoxicity of paclitaxel.
+19473225|a|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.
+19473225	10	19	glutamate	Chemical	D018698
+19473225	62	86	peripheral neurotoxicity	Disease	D010523
+19473225	90	100	paclitaxel	Chemical	D017239
+19473225	108	129	peripheral neuropathy	Disease	D010523
+19473225	191	201	paclitaxel	Chemical	D017239
+19473225	203	206	PAC	Chemical	D017239
+19473225	218	227	glutamate	Chemical	D018698
+19473225	252	262	amino acid	Chemical	D000596
+19473225	263	272	glutamine	Chemical	D018698
+19473225	300	303	PAC	Chemical	D017239
+19473225	304	317	neurotoxicity	Disease	D020258
+19473225	366	375	glutamate	Chemical	D018698
+19473225	407	410	PAC	Chemical	D017239
+19473225	419	440	peripheral neuropathy	Disease	D010523
+19473225	544	558	ovarian cancer	Disease	D010051
+19473225	629	632	PAC	Chemical	D017239
+19473225	681	690	glutamate	Chemical	D018698
+19473225	1032	1045	neurotoxicity	Disease	D020258
+19473225	1201	1205	pain	Disease	D010146
+19473225	1409	1418	glutamate	Chemical	D018698
+19473225	1482	1506	peripheral neurotoxicity	Disease	D010523
+19473225	1510	1513	PAC	Chemical	D017239
+19473225	CID	D017239	D010523
+
+19387625|t|Attentional modulation of perceived pain intensity in capsaicin-induced secondary hyperalgesia.
+19387625|a|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.
+19387625	36	40	pain	Disease	D010146
+19387625	54	63	capsaicin	Chemical	D002211
+19387625	82	94	hyperalgesia	Disease	D006930
+19387625	106	110	pain	Disease	D010146
+19387625	182	186	pain	Disease	D010146
+19387625	234	243	capsaicin	Chemical	D002211
+19387625	262	274	hyperalgesia	Disease	D006930
+19387625	304	308	pain	Disease	D010146
+19387625	332	344	hyperalgesia	Disease	D006930
+19387625	531	543	hyperalgesia	Disease	D006930
+19387625	571	580	capsaicin	Chemical	D002211
+19387625	656	665	capsaicin	Chemical	D002211
+19387625	716	725	capsaicin	Chemical	D002211
+19387625	744	756	hyperalgesia	Disease	D006930
+19387625	795	799	pain	Disease	D010146
+19387625	CID	D002211	D006930
+
+19211690|t|Testosterone-dependent hypertension and upregulation of intrarenal angiotensinogen in Dahl salt-sensitive rats.
+19211690|a|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.
+19211690	0	12	Testosterone	Chemical	D013739	
+19211690	23	35	hypertension	Disease	D006973	
+19211690	91	95	salt	Chemical	D017673	
+19211690	140	144	salt	Chemical	D017673	
+19211690	199	203	salt	Chemical	D017673	
+19211690	230	234	salt	Chemical	D017673	
+19211690	320	331	angiotensin	Chemical	D000809	
+19211690	638	650	testosterone	Chemical	D013739	
+19211690	688	700	renal injury	Disease	D007674	
+19211690	711	715	salt	Chemical	D017673	
+19211690	1190	1210	glomerular sclerosis	Disease	D007674	
+19211690	1265	1277	Testosterone	Chemical	D013739	
+19211690	1325	1337	renal injury	Disease	D007674	
+19211690	1406	1418	Testosterone	Chemical	D013739	
+19211690	1453	1465	hypertension	Disease	D006973	
+19211690	1470	1482	renal injury	Disease	D007674	
+19211690	1564	1575	angiotensin	Chemical	D000809	
+19211690	CID	D017673	D007674
+
+18703024|t|Prenatal protein deprivation alters dopamine-mediated behaviors and dopaminergic and glutamatergic receptor binding.
+18703024|a|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.
+18703024	36	44	dopamine	Chemical	D004298
+18703024	215	228	schizophrenia	Disease	D012559
+18703024	390	403	schizophrenia	Disease	D012559
+18703024	509	520	apomorphine	Chemical	D001058
+18703024	560	571	amphetamine	Chemical	D000661
+18703024	652	663	haloperidol	Chemical	D006220
+18703024	672	681	catalepsy	Disease	D002375
+18703024	685	691	MK-801	Chemical	D016291
+18703024	783	784	H	Chemical	D006859
+18703024	785	791	MK-801	Chemical	D016291
+18703024	896	897	H	Chemical	D006859
+18703024	898	909	haloperidol	Chemical	D006220
+18703024	932	940	dopamine	Chemical	D004298
+18703024	1101	1102	H	Chemical	D006859
+18703024	1103	1109	MK-801	Chemical	D016291
+18703024	1205	1227	nutritional deficiency	Disease	D044342
+18703024	1246	1259	schizophrenia	Disease	D012559
+18703024	CID	D006220	D002375
+
+18631865|t|mToR inhibitors-induced proteinuria: mechanisms, significance, and management.
+18631865|a|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.
+18631865	24	35	proteinuria	Disease	D011507
+18631865	199	208	rapamycin	Chemical	D020123
+18631865	239	248	sirolimus	Chemical	D020123
+18631865	286	315	chronic allograft nephropathy	Disease	D051436
+18631865	325	336	proteinuria	Disease	D011507
+18631865	473	484	proteinuria	Disease	D011507
+18631865	496	505	sirolimus	Chemical	D020123
+18631865	600	611	proteinuria	Disease	D011507
+18631865	637	646	sirolimus	Chemical	D020123
+18631865	709	718	sirolimus	Chemical	D020123
+18631865	764	782	glomerulosclerosis	Disease	D005921
+18631865	987	998	proteinuria	Disease	D011507
+18631865	CID	D020123	D011507
+
+18162529|t|Hypothalamic prolactin receptor messenger ribonucleic acid levels, prolactin signaling, and hyperprolactinemic inhibition of pulsatile luteinizing hormone secretion are dependent on estradiol.
+18162529|a|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.
+18162529	42	58	ribonucleic acid	Chemical	D012313
+18162529	92	110	hyperprolactinemic	Disease	D006966
+18162529	182	191	estradiol	Chemical	D004958
+18162529	193	211	Hyperprolactinemia	Disease	D006966
+18162529	385	403	hyperprolactinemia	Disease	D006966
+18162529	507	515	estrogen	Chemical	D004967
+18162529	542	560	hyperprolactinemia	Disease	D006966
+18162529	576	584	dopamine	Chemical	D004298
+18162529	596	605	sulpiride	Chemical	D013469
+18162529	722	731	estradiol	Chemical	D004958
+18162529	733	742	Sulpiride	Chemical	D013469
+18162529	777	784	steroid	Chemical	D013256
+18162529	864	873	Estradiol	Chemical	D004958
+18162529	1032	1040	estrogen	Chemical	D004967
+18162529	1124	1133	estradiol	Chemical	D004958
+18162529	1343	1352	sulpiride	Chemical	D013469
+18162529	1357	1366	estradiol	Chemical	D004958
+18162529	1368	1377	Sulpiride	Chemical	D013469
+18162529	1562	1571	Estradiol	Chemical	D004958
+18162529	1629	1638	estradiol	Chemical	D004958
+18162529	1768	1786	hyperprolactinemia	Disease	D006966
+18162529	1792	1799	steroid	Chemical	D013256
+18162529	1849	1858	estradiol	Chemical	D004958
+18162529	CID	D013469	D006966
+
+17879945|t|Estrogen prevents cholesteryl ester accumulation in macrophages induced by the HIV protease inhibitor ritonavir.
+17879945|a|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.
+17879945	18	35	cholesteryl ester	Chemical	D002788
+17879945	102	111	ritonavir	Chemical	D019438
+17879945	224	233	ritonavir	Chemical	D019438
+17879945	307	332	premature atherosclerosis	Disease	D050197
+17879945	371	380	ritonavir	Chemical	D019438
+17879945	401	423	atherosclerotic lesion	Disease	D050197
+17879945	542	551	ritonavir	Chemical	D019438
+17879945	577	594	cholesteryl ester	Chemical	D002788
+17879945	712	723	cholesterol	Chemical	D002784
+17879945	792	801	ritonavir	Chemical	D019438
+17879945	1026	1042	17beta-estradiol	Chemical	D004958	
+17879945	1044	1046	E2	Chemical	D004958
+17879945	1056	1068	progesterone	Chemical	D011374
+17879945	1087	1094	ethanol	Chemical	D000431
+17879945	1135	1144	ritonavir	Chemical	D019438
+17879945	1267	1269	E2	Chemical	D004958
+17879945	1300	1318	cholesteryl esters	Chemical	D002788
+17879945	1344	1353	ritonavir	Chemical	D019438
+17879945	1365	1374	Ritonavir	Chemical	D019438
+17879945	1487	1496	ritonavir	Chemical	D019438
+17879945	1662	1664	E2	Chemical	D004958
+17879945	1728	1730	E2	Chemical	D004958
+17879945	1860	1862	E2	Chemical	D004958
+17879945	1983	2000	cholesteryl ester	Chemical	D002788
+17879945	2024	2033	ritonavir	Chemical	D019438
+17879945	CID	D019438	D050197
+
+17437408|t|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.
+17437408|a|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.
+17437408	90	97	seizure	Disease	D012640
+17437408	861	870	phenytoin	Chemical	D010672
+17437408	1987	1998	pilocarpine	Chemical	D010862
+17437408	2007	2015	seizures	Disease	D012640
+17437408	2104	2117	phenobarbital	Chemical	D010634
+17437408	2150	2160	tariquidar	Chemical	C402343
+17437408	2457	2476	injury to the brain	Disease	D001927
+17437408	2784	2792	seizures	Disease	D012640
+17437408	CID	D010862	D012640
+
+17242861|t|Use of chromosome substitution strains to identify seizure susceptibility loci in mice.
+17242861|a|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.
+17242861	51	58	seizure	Disease	D012640
+17242861	88	95	Seizure	Disease	D012640
+17242861	394	401	seizure	Disease	D012640
+17242861	445	456	pilocarpine	Chemical	D010862
+17242861	465	473	seizures	Disease	D012640
+17242861	486	508	temporal lobe epilepsy	Disease	D004833
+17242861	584	591	seizure	Disease	D012640
+17242861	730	741	pilocarpine	Chemical	D010862
+17242861	750	758	seizures	Disease	D012640
+17242861	858	869	pilocarpine	Chemical	D010862
+17242861	878	886	seizures	Disease	D012640
+17242861	990	998	seizures	Disease	D012640
+17242861	1265	1272	seizure	Disease	D012640
+17242861	1431	1453	temporal lobe epilepsy	Disease	D004833
+17242861	CID	D010862	D004833
+
+16337777|t|Investigation of mitochondrial involvement in the experimental model of epilepsy induced by pilocarpine.
+16337777|a|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.
+16337777	72	80	epilepsy	Disease	D004827
+16337777	92	103	pilocarpine	Chemical	D010862
+16337777	105	132	Mitochondrial abnormalities	Disease	D028361
+16337777	238	243	death	Disease	D003643
+16337777	537	555	status epilepticus	Disease	D013226
+16337777	741	752	pilocarpine	Chemical	D010862
+16337777	762	784	temporal lobe epilepsy	Disease	D004833
+16337777	1231	1258	mitochondrial abnormalities	Disease	D028361
+16337777	CID	D010862	D004833
+
+15859940|t|Causes of acute thrombotic microangiopathy in patients receiving kidney transplantation.
+15859940|a|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%).
+15859940	16	42	thrombotic microangiopathy	Disease	D057049
+15859940	101	127	Thrombotic microangiopathy	Disease	D057049
+15859940	227	253	thrombotic microangiopathy	Disease	D057049
+15859940	279	304	hemolytic uremic syndrome	Disease	D006463
+15859940	342	368	thrombotic microangiopathy	Disease	D057049
+15859940	502	528	thrombotic microangiopathy	Disease	D057049
+15859940	824	850	thrombotic microangiopathy	Disease	D057049
+15859940	1095	1107	cyclosporine	Chemical	D016572
+15859940	1142	1154	cyclosporine	Chemical	D016572
+15859940	1159	1169	tacrolimus	Chemical	D016559
+15859940	1202	1228	thrombotic microangiopathy	Disease	D057049
+15859940	1243	1268	antiphospholipid syndrome	Disease	D016736
+15859940	1287	1315	systemic lupus erythematosus	Disease	D008180
+15859940	1376	1401	hemolytic uremic syndrome	Disease	D006463
+15859940	1467	1492	hemolytic uremic syndrome	Disease	D006463
+15859940	1529	1541	cyclosporine	Chemical	D016572
+15859940	1543	1553	tacrolimus	Chemical	D016559
+15859940	1555	1563	toxicity	Disease	D064420
+15859940	1660	1686	thrombotic microangiopathy	Disease	D057049
+15859940	1725	1737	cyclosporine	Chemical	D016572
+15859940	1778	1804	thrombotic microangiopathy	Disease	D057049
+15859940	CID	D016572	D057049
+
+15188772|t|Severe reversible left ventricular systolic and diastolic dysfunction due to accidental iatrogenic epinephrine overdose.
+15188772|a|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.
+15188772	18	69	left ventricular systolic and diastolic dysfunction	Disease	D018487
+15188772	99	110	epinephrine	Chemical	D004837
+15188772	111	119	overdose	Disease	D062787
+15188772	121	134	Catecholamine	Chemical	D002395
+15188772	143	157	cardiomyopathy	Disease	D009202
+15188772	194	208	catecholamines	Chemical	D002395
+15188772	291	313	myocardial dysfunction	Disease	D009202
+15188772	338	346	overdose	Disease	D062787
+15188772	436	447	epinephrine	Chemical	D004837
+15188772	458	477	myocardial stunning	Disease	D017682
+15188772	563	614	left ventricular systolic and diastolic dysfunction	Disease	D018487
+15188772	666	685	myocardial necrosis	Disease	D009202
+15188772	CID	D004837	D017682
+
+15130900|t|Urinary bladder cancer in Wegener's granulomatosis: risks and relation to cyclophosphamide.
+15130900|a|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.
+15130900	0	22	Urinary bladder cancer	Disease	D001749
+15130900	26	50	Wegener's granulomatosis	Disease	D014890
+15130900	74	90	cyclophosphamide	Chemical	D003520
+15130900	142	156	bladder cancer	Disease	D001749
+15130900	178	194	cyclophosphamide	Chemical	D003520
+15130900	213	237	Wegener's granulomatosis	Disease	D014890
+15130900	342	366	Wegener's granulomatosis	Disease	D014890
+15130900	426	432	Cancer	Disease	D009369
+15130900	486	500	bladder cancer	Disease	D001749
+15130900	623	639	cyclophosphamide	Chemical	D003520
+15130900	644	658	bladder cancer	Disease	D001749
+15130900	738	752	bladder cancer	Disease	D001749
+15130900	759	783	Wegener's granulomatosis	Disease	D014890
+15130900	829	843	bladder cancer	Disease	D001749
+15130900	872	896	Wegener's granulomatosis	Disease	D014890
+15130900	959	975	cyclophosphamide	Chemical	D003520
+15130900	1066	1080	bladder cancer	Disease	D001749
+15130900	1117	1133	cyclophosphamide	Chemical	D003520
+15130900	1325	1339	bladder cancer	Disease	D001749
+15130900	1394	1418	Wegener's granulomatosis	Disease	D014890
+15130900	1437	1451	bladder cancer	Disease	D001749
+15130900	1532	1556	Wegener's granulomatosis	Disease	D014890
+15130900	1628	1644	cyclophosphamide	Chemical	D003520
+15130900	1661	1675	bladder cancer	Disease	D001749
+15130900	1784	1808	Wegener's granulomatosis	Disease	D014890
+15130900	CID	D003520	D001749
+
+12707296|t|L-arginine transport in humans with cortisol-induced hypertension.
+12707296|a|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.
+12707296	0	10	L-arginine	Chemical	D001120
+12707296	36	44	cortisol	Chemical	D006854
+12707296	53	65	hypertension	Disease	D006973
+12707296	79	89	L-arginine	Chemical	D001120
+12707296	90	102	nitric oxide	Chemical	D009569
+12707296	127	135	cortisol	Chemical	D006854
+12707296	144	156	hypertension	Disease	D006973
+12707296	198	208	L-arginine	Chemical	D001120
+12707296	281	303	Hydrocortisone acetate	Chemical	C021650
+12707296	570	580	L-arginine	Chemical	D001120
+12707296	637	647	L-arginine	Chemical	D001120
+12707296	696	711	[3H]-l-arginine	Chemical	D001120
+12707296	763	778	[3H]-L-arginine	Chemical	D001120
+12707296	823	838	[3H]-L-arginine	Chemical	D001120
+12707296	969	979	L-arginine	Chemical	D001120
+12707296	999	1007	cortisol	Chemical	D006854
+12707296	1185	1195	L-arginine	Chemical	D001120
+12707296	1327	1337	l-arginine	Chemical	D001120
+12707296	1375	1385	L-arginine	Chemical	D001120
+12707296	1534	1542	cortisol	Chemical	D006854
+12707296	1563	1573	L-arginine	Chemical	D001120
+12707296	1611	1619	cortisol	Chemical	D006854
+12707296	1648	1656	cortisol	Chemical	D006854
+12707296	1665	1692	increases in blood pressure	Disease	D006973
+12707296	1738	1748	l-arginine	Chemical	D001120
+12707296	CID	C021650	D006973
+
+12695819|t|MR imaging with quantitative diffusion mapping of tacrolimus-induced neurotoxicity in organ transplant patients.
+12695819|a|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.
+12695819	50	60	tacrolimus	Chemical	D016559
+12695819	69	82	neurotoxicity	Disease	D020258
+12695819	293	303	tacrolimus	Chemical	D016559
+12695819	424	434	tacrolimus	Chemical	D016559
+12695819	449	473	neurologic complications	Disease	D009422
+12695819	741	767	white matter abnormalities	Disease	D056784
+12695819	782	802	putaminal hemorrhage	Disease	D020146
+12695819	886	912	white matter abnormalities	Disease	D056784
+12695819	1153	1178	cortical laminar necrosis	Disease	D001927
+12695819	1266	1276	tacrolimus	Chemical	D016559
+12695819	1285	1298	neurotoxicity	Disease	D020258
+12695819	CID	D016559	D056784
+
+12596116|t|Octreotide-induced hypoxemia and pulmonary hypertension in premature neonates.
+12596116|a|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.
+12596116	0	10	Octreotide	Chemical	D015282
+12596116	19	28	hypoxemia	Disease	D000860
+12596116	33	55	pulmonary hypertension	Disease	D006976
+12596116	152	159	fistula	Disease	D005402
+12596116	173	198	necrotizing enterocolitis	Disease	D020345
+12596116	200	222	Pulmonary hypertension	Disease	D006976
+12596116	282	292	octreotide	Chemical	D015282
+12596116	323	330	fistula	Disease	D005402
+12596116	CID	D015282	D006976
+
+11875660|t|Sequential observations of exencephaly and subsequent morphological changes by mouse exo utero development system: analysis of the mechanism of transformation from exencephaly to anencephaly.
+11875660|a|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.
+11875660	27	38	exencephaly	Disease	D009436
+11875660	164	175	exencephaly	Disease	D009436
+11875660	179	190	anencephaly	Disease	D000757
+11875660	192	203	Anencephaly	Disease	D000757
+11875660	239	250	exencephaly	Disease	D009436
+11875660	543	554	exencephaly	Disease	D009436
+11875660	566	579	5-azacytidine	Chemical	D001374
+11875660	751	762	exencephaly	Disease	D009436
+11875660	766	777	anencephaly	Disease	D000757
+11875660	807	819	exencephalic	Disease	D009436
+11875660	953	964	exencephaly	Disease	D009436
+11875660	990	1002	exencephalic	Disease	D009436
+11875660	1089	1101	exencephalic	Disease	D009436
+11875660	1157	1168	anencephaly	Disease	D000757
+11875660	1223	1235	exencephalic	Disease	D009436
+11875660	1305	1316	exencephaly	Disease	D009436
+11875660	1336	1348	hemorrhaging	Disease	D006470
+11875660	1413	1425	exencephalic	Disease	D009436
+11875660	1480	1492	exencephalic	Disease	D009436
+11875660	1612	1624	exencephalic	Disease	D009436
+11875660	1677	1689	exencephalic	Disease	D009436
+11875660	1779	1798	circulatory failure	Disease	D012769
+11875660	1806	1818	hemorrhaging	Disease	D006470
+11875660	1843	1855	exencephalic	Disease	D009436
+11875660	1939	1950	exencephaly	Disease	D009436
+11875660	1954	1965	anencephaly	Disease	D000757
+11875660	CID	D001374	D000757
+
+11166519|t|Acute cocaine-induced seizures: differential sensitivity of six inbred mouse strains.
+11166519|a|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.
+11166519	6	13	cocaine	Chemical	D003042
+11166519	22	30	seizures	Disease	D012640
+11166519	182	190	seizures	Disease	D012640
+11166519	224	231	cocaine	Chemical	D003042
+11166519	233	240	Cocaine	Chemical	D003042
+11166519	337	344	Seizure	Disease	D012640
+11166519	431	438	seizure	Disease	D012640
+11166519	471	478	seizure	Disease	D012640
+11166519	837	844	cocaine	Chemical	D003042
+11166519	1039	1046	cocaine	Chemical	D003042
+11166519	1055	1063	seizures	Disease	D012640
+11166519	CID	D003042	D012640
+
+8701950|t|Microangiopathic hemolytic anemia complicating FK506 (tacrolimus) therapy.
+8701950|a|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.
+8701950	0	33	Microangiopathic hemolytic anemia	Disease	D000743
+8701950	47	52	FK506	Chemical	D016559
+8701950	54	64	tacrolimus	Chemical	D016559
+8701950	101	134	microangiopathic hemolytic anemia	Disease	D000743
+8701950	136	140	MAHA	Disease	D000743
+8701950	176	181	FK506	Chemical	D016559
+8701950	183	193	tacrolimus	Chemical	D016559
+8701950	238	243	FK506	Chemical	D016559
+8701950	313	328	corticosteroids	Chemical	D000305
+8701950	330	337	aspirin	Chemical	D001241
+8701950	343	355	dipyridamole	Chemical	D004176
+8701950	377	381	MAHA	Disease	D000743
+8701950	417	422	FK506	Chemical	D016559
+8701950	450	454	MAHA	Disease	D000743
+8701950	456	461	FK506	Chemical	D016559
+8701950	473	477	MAHA	Disease	D000743
+8701950	604	609	FK506	Chemical	D016559
+8701950	644	657	cyclosporin A	Chemical	D016572
+8701950	659	662	CyA	Chemical	D016572
+8701950	716	720	MAHA	Disease	D000743
+8701950	CID	D016559	D000743
+
+7292072|t|Variant ventricular tachycardia in desipramine toxicity.
+7292072|a|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.
+7292072	8	31	ventricular tachycardia	Disease	D017180
+7292072	35	46	desipramine	Chemical	D003891
+7292072	47	55	toxicity	Disease	D064420
+7292072	85	108	ventricular tachycardia	Disease	D017180
+7292072	120	131	desipramine	Chemical	D003891
+7292072	132	140	toxicity	Disease	D064420
+7292072	166	176	arrhythmia	Disease	D001145
+7292072	410	433	ventricular tachycardia	Disease	D017180
+7292072	492	515	ventricular tachycardia	Disease	D017180
+7292072	CID	D003891	D017180
+
+4027862|t|Desipramine-induced delirium at "subtherapeutic" concentrations: a case report.
+4027862|a|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.
+4027862	0	11	Desipramine	Chemical	D003891
+4027862	20	28	delirium	Disease	D003693
+4027862	121	132	Desipramine	Chemical	D003891
+4027862	145	153	delirium	Disease	D003693
+4027862	212	220	Delirium	Disease	D003693
+4027862	370	385	antidepressants	Chemical	D000928
+4027862	CID	D003891	D003693
+
+2484011|t|Mouse strain-dependent effect of amantadine on motility and brain biogenic amines.
+2484011|a|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.
+2484011	33	43	amantadine	Chemical	D000547
+2484011	75	81	amines	Chemical	D000588
+2484011	97	121	amantadine hydrochloride	Chemical	D000547
+2484011	246	252	amines	Chemical	D000588
+2484011	415	425	Amantadine	Chemical	D000547
+2484011	502	512	amantadine	Chemical	D000547
+2484011	513	522	depressed	Disease	D003866
+2484011	629	639	amantadine	Chemical	D000547
+2484011	952	962	amantadine	Chemical	D000547
+2484011	994	1004	amantadine	Chemical	D000547
+2484011	1147	1170	suppression of motility	Disease	D011596
+2484011	1196	1206	amantadine	Chemical	D000547
+2484011	1233	1241	dopamine	Chemical	D004298
+2484011	1278	1308	3,4-dihydroxyphenylacetic acid	Chemical	D015102
+2484011	1374	1389	normetanephrine	Chemical	D009647
+2484011	1441	1451	amantadine	Chemical	D000547
+2484011	1521	1531	amantadine	Chemical	D000547
+2484011	1749	1759	amantadine	Chemical	D000547
+2484011	1803	1809	amines	Chemical	D000588
+2484011	1864	1877	catecholamine	Chemical	D002395
+2484011	1976	1990	norepinephrine	Chemical	D009638
+2484011	2015	2036	behavioral depression	Disease	D011596
+2484011	2047	2057	amantadine	Chemical	D000547
+2484011	CID	D000547	D011596
+
+2396046|t|No enhancement by phenobarbital of the hepatocarcinogenicity of a choline-devoid diet in the rat.
+2396046|a|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.
+2396046	18	31	phenobarbital	Chemical	D010634
+2396046	66	73	choline	Chemical	D002794
+2396046	155	168	phenobarbital	Chemical	D010634
+2396046	174	181	choline	Chemical	D002794
+2396046	329	336	choline	Chemical	D002794
+2396046	347	354	choline	Chemical	D002794
+2396046	399	412	phenobarbital	Chemical	D010634
+2396046	450	475	hepatocellular carcinomas	Disease	D006528
+2396046	508	515	choline	Chemical	D002794
+2396046	574	598	hepatocellular carcinoma	Disease	D006528
+2396046	650	663	phenobarbital	Chemical	D010634
+2396046	711	736	hepatocellular carcinomas	Disease	D006528
+2396046	790	797	choline	Chemical	D002794
+2396046	844	857	phenobarbital	Chemical	D010634
+2396046	869	876	choline	Chemical	D002794
+2396046	961	968	choline	Chemical	D002794
+2396046	984	997	phenobarbital	Chemical	D010634
+2396046	CID	D002794	D006528
+
+2008831|t|Effect of direct intracoronary administration of methylergonovine in patients with and without variant angina.
+2008831|a|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.
+2008831	49	65	methylergonovine	Chemical	D008755
+2008831	95	109	variant angina	Disease	D000788
+2008831	158	174	methylergonovine	Chemical	D008755
+2008831	208	222	variant angina	Disease	D000788
+2008831	253	263	chest pain	Disease	D002637
+2008831	286	301	angina pectoris	Disease	D000787
+2008831	319	335	Methylergonovine	Chemical	D008755
+2008831	439	453	variant angina	Disease	D000788
+2008831	455	469	coronary spasm	Disease	D003329
+2008831	599	604	spasm	Disease	D013035
+2008831	877	882	spasm	Disease	D013035
+2008831	967	983	methylergonovine	Chemical	D008755
+2008831	1012	1026	variant angina	Disease	D000788
+2008831	CID	D008755	D003329
+
+1732369|t|Dobutamine stress echocardiography: a sensitive indicator of diminished myocardial function in asymptomatic doxorubicin-treated long-term survivors of childhood cancer.
+1732369|a|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)
+1732369	0	10	Dobutamine	Chemical	D004280
+1732369	108	119	doxorubicin	Chemical	D004317
+1732369	161	167	cancer	Disease	D009369
+1732369	169	180	Doxorubicin	Chemical	D004317
+1732369	264	278	cardiomyopathy	Disease	D009202
+1732369	345	359	cardiac damage	Disease	D006331
+1732369	367	378	doxorubicin	Chemical	D004317
+1732369	415	425	dobutamine	Chemical	D004280
+1732369	498	504	cancer	Disease	D009369
+1732369	518	529	doxorubicin	Chemical	D004317
+1732369	739	750	doxorubicin	Chemical	D004317
+1732369	856	866	dobutamine	Chemical	D004280
+1732369	1048	1058	Dobutamine	Chemical	D004280
+1732369	1382	1393	doxorubicin	Chemical	D004317
+1732369	1497	1507	dobutamine	Chemical	D004280
+1732369	1596	1607	doxorubicin	Chemical	D004317
+1732369	1790	1800	dobutamine	Chemical	D004280
+1732369	1818	1829	doxorubicin	Chemical	D004317
+1732369	CID	D004317	D009202
+
+234669|t|Effects of aminophylline on the threshold for initiating ventricular fibrillation during respiratory failure.
+234669|a|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.
+234669	11	24	aminophylline	Chemical	D000628
+234669	57	81	ventricular fibrillation	Disease	D014693
+234669	89	108	respiratory failure	Disease	D012131
+234669	110	129	Cardiac arrhythmias	Disease	D001145
+234669	180	199	respiratory failure	Disease	D012131
+234669	269	289	cardiac disturbances	Disease	D006331
+234669	307	326	respiratory failure	Disease	D012131
+234669	377	390	aminophylline	Chemical	D000628
+234669	398	422	ventricular fibrillation	Disease	D014693
+234669	479	498	respiratory failure	Disease	D012131
+234669	549	573	ventricular fibrillation	Disease	D014693
+234669	761	774	aminophylline	Chemical	D000628
+234669	780	804	ventricular fibrillation	Disease	D014693
+234669	895	901	oxygen	Chemical	D010100
+234669	903	906	PO2	Chemical	C093415
+234669	912	926	carbon dioxide	Chemical	D002245
+234669	928	931	CO2	Chemical	D002245
+234669	970	989	respiratory failure	Disease	D012131
+234669	1006	1021	hypoventilation	Disease	D007040
+234669	1095	1108	aminophylline	Chemical	D000628
+234669	1149	1173	ventricular fibrillation	Disease	D014693
+234669	1318	1341	ventricular arrhythmias	Disease	D001145
+234669	1345	1364	respiratory failure	Disease	D012131
+234669	1401	1414	aminophylline	Chemical	D000628
+234669	CID	D000628	D014693
+
+16740173|t|Case report: acute unintentional carbachol intoxication.
+16740173|a|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.
+16740173	33	42	carbachol	Chemical	D002217
+16740173	90	99	carbachol	Chemical	D002217
+16740173	212	221	poisoning	Disease	D011041
+16740173	341	360	Alzheimer's disease	Disease	D000544
+16740173	442	456	carbamylcholin	Chemical	D002217
+16740173	468	477	carbachol	Chemical	D002217
+16740173	497	506	carbachol	Chemical	D002217
+16740173	587	596	Carbachol	Chemical	D002217
+16740173	775	781	nausea	Disease	D009325
+16740173	796	807	hypotension	Disease	D007022
+16740173	832	843	Bradycardia	Disease	D001919
+16740173	870	878	asystole	Disease	D006323
+16740173	956	966	adrenaline	Chemical	D004837
+16740173	968	979	epinephrine	Chemical	D004837
+16740173	982	990	atropine	Chemical	D001285
+16740173	995	1005	furosemide	Chemical	D005665
+16740173	1138	1151	hyperhidrosis	Disease	D006945
+16740173	1153	1168	hypersalivation	Disease	D012798
+16740173	1170	1183	bronchorrhoea	Disease	-1
+16740173	1196	1202	miosis	Disease	D015877
+16740173	1241	1271	atrio-ventricular dissociation	Disease	D006327
+16740173	1287	1295	atropine	Chemical	D001285
+16740173	1324	1334	adrenaline	Chemical	D004837
+16740173	1339	1347	dopamine	Chemical	D004298
+16740173	1423	1431	dyspnoea	Disease	D004417
+16740173	1436	1448	bronchospasm	Disease	D001986
+16740173	1476	1501	Respiratory insufficiency	Disease	D012131
+16740173	1526	1553	Proteus mirabilis infection	Disease	D011512
+16740173	1738	1751	heart failure	Disease	D006333
+16740173	1825	1834	carbachol	Chemical	D002217
+16740173	2208	2217	carbachol	Chemical	D002217
+16740173	2271	2280	carbachol	Chemical	D002217
+16740173	2495	2523	acute cardiovascular failure	Disease	D002318
+16740173	CID	D002217	D009325
+16740173	CID	D002217	D001919
+16740173	CID	D002217	D006323
+16740173	CID	D002217	D006333
+16740173	CID	D002217	D007022
+16740173	CID	D002217	D015877
+16740173	CID	D002217	D006945
+16740173	CID	D002217	D012798
+
+12464714|t|Crossover comparison of efficacy and preference for rizatriptan 10 mg versus ergotamine/caffeine in migraine.
+12464714|a|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%).
+12464714	52	63	rizatriptan	Chemical	C093622
+12464714	77	87	ergotamine	Chemical	D004878
+12464714	88	96	caffeine	Chemical	D002110
+12464714	100	108	migraine	Disease	D008881
+12464714	110	121	Rizatriptan	Chemical	C093622
+12464714	137	141	5-HT	Chemical	D012701
+12464714	245	253	migraine	Disease	D008881
+12464714	342	353	rizatriptan	Chemical	C093622
+12464714	372	382	ergotamine	Chemical	D004878
+12464714	388	396	caffeine	Chemical	D002110
+12464714	446	454	migraine	Disease	D008881
+12464714	560	571	rizatriptan	Chemical	C093622
+12464714	575	585	ergotamine	Chemical	D004878
+12464714	586	594	caffeine	Chemical	D002110
+12464714	646	654	headache	Disease	D006261
+12464714	739	750	rizatriptan	Chemical	C093622
+12464714	787	797	ergotamine	Chemical	D004878
+12464714	798	806	caffeine	Chemical	D002110
+12464714	841	845	pain	Disease	D010146
+12464714	879	890	rizatriptan	Chemical	C093622
+12464714	928	932	pain	Disease	D010146
+12464714	948	959	rizatriptan	Chemical	C093622
+12464714	994	1004	ergotamine	Chemical	D004878
+12464714	1005	1013	caffeine	Chemical	D002110
+12464714	1032	1043	rizatriptan	Chemical	C093622
+12464714	1084	1092	Headache	Disease	D006261
+12464714	1121	1132	rizatriptan	Chemical	C093622
+12464714	1147	1157	ergotamine	Chemical	D004878
+12464714	1158	1166	caffeine	Chemical	D002110
+12464714	1190	1201	rizatriptan	Chemical	C093622
+12464714	1220	1230	ergotamine	Chemical	D004878
+12464714	1231	1239	caffeine	Chemical	D002110
+12464714	1295	1306	rizatriptan	Chemical	C093622
+12464714	1312	1316	pain	Disease	D010146
+12464714	1429	1439	ergotamine	Chemical	D004878
+12464714	1440	1448	caffeine	Chemical	D002110
+12464714	1467	1478	Rizatriptan	Chemical	C093622
+12464714	1500	1510	ergotamine	Chemical	D004878
+12464714	1511	1519	caffeine	Chemical	D002110
+12464714	1559	1565	nausea	Disease	D009325
+12464714	1567	1575	vomiting	Disease	D014839
+12464714	1577	1588	phonophobia	Disease	D012001
+12464714	1592	1603	photophobia	Disease	D020795
+12464714	1767	1778	rizatriptan	Chemical	C093622
+12464714	1820	1830	ergotamine	Chemical	D004878
+12464714	1831	1839	caffeine	Chemical	D002110
+12464714	1898	1909	rizatriptan	Chemical	C093622
+12464714	1925	1935	ergotamine	Chemical	D004878
+12464714	1936	1944	caffeine	Chemical	D002110
+12464714	2062	2073	rizatriptan	Chemical	C093622
+12464714	2078	2088	ergotamine	Chemical	D004878
+12464714	2089	2097	caffeine	Chemical	D002110
+12464714	2118	2127	dizziness	Disease	D004244
+12464714	2144	2150	nausea	Disease	D009325
+12464714	2170	2180	somnolence	Disease	D006970
+12464714	CID	C093622	D009325
+12464714	CID	C093622	D004244
+
+6203452|t|Thrombotic microangiopathy and renal failure associated with antineoplastic chemotherapy.
+6203452|a|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.
+6203452	0	26	Thrombotic microangiopathy	Disease	D057049
+6203452	31	44	renal failure	Disease	D051437
+6203452	109	118	carcinoma	Disease	D002277
+6203452	129	155	thrombotic microangiopathy	Disease	D057049
+6203452	174	193	renal insufficiency	Disease	D051437
+6203452	195	228	microangiopathic hemolytic anemia	Disease	D000743
+6203452	242	258	thrombocytopenia	Disease	D013921
+6203452	281	290	cisplatin	Chemical	D002945
+6203452	292	301	bleomycin	Chemical	D001761
+6203452	309	323	vinca alkaloid	Chemical	D014748
+6203452	341	376	thrombotic thrombocytopenic purpura	Disease	D011697
+6203452	388	413	hemolytic-uremic syndrome	Disease	D006463
+6203452	537	562	intravascular coagulation	Disease	D004211
+6203452	656	661	tumor	Disease	D009369
+6203452	687	692	tumor	Disease	D009369
+6203452	728	754	thrombotic microangiopathy	Disease	D057049
+6203452	939	952	renal failure	Disease	D051437
+6203452	972	981	cisplatin	Chemical	D002945
+6203452	982	996	nephrotoxicity	Disease	D007674
+6203452	1005	1011	anemia	Disease	D000740
+6203452	1016	1032	thrombocytopenia	Disease	D013921
+6203452	1049	1072	bone marrow suppression	Disease	D001855
+6203452	CID	D001761	D011697
+6203452	CID	D014748	D006463
+6203452	CID	D002945	D007674
+6203452	CID	D014748	D007674
+6203452	CID	D002945	D011697
+6203452	CID	D001761	D006463
+6203452	CID	D014748	D011697
+6203452	CID	D002945	D006463
+6203452	CID	D001761	D007674
+
+20528871|t|Salvage therapy with nelarabine, etoposide, and cyclophosphamide in relapsed/refractory paediatric T-cell lymphoblastic leukaemia and lymphoma.
+20528871|a|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.
+20528871	21	31	nelarabine	Chemical	C104457
+20528871	33	42	etoposide	Chemical	D005047
+20528871	48	64	cyclophosphamide	Chemical	D003520
+20528871	99	142	T-cell lymphoblastic leukaemia and lymphoma	Disease	D015458|D016399	T-cell lymphoblastic leukaemia|T-cell lymphoblastic lymphoma
+20528871	168	178	nelarabine	Chemical	C104457
+20528871	180	184	AraG	Chemical	C104457
+20528871	198	207	etoposide	Chemical	D005047
+20528871	209	211	VP	Chemical	D005047
+20528871	217	233	cyclophosphamide	Chemical	D003520
+20528871	235	238	CPM	Chemical	D003520
+20528871	356	384	T-cell leukaemia or lymphoma	Disease	D015458|D016399	T-cell leukaemia|T-cell lymphoma
+20528871	435	439	AraG	Chemical	C104457
+20528871	481	491	neuropathy	Disease	D009422
+20528871	496	516	musculoskeletal pain	Disease	D059352
+20528871	518	541	Haematological toxicity	Disease	D006402
+20528871	579	583	AraG	Chemical	C104457
+20528871	827	831	AraG	Chemical	C104457
+20528871	832	834	VP	Chemical	D005047
+20528871	835	838	CPM	Chemical	D003520
+20528871	885	889	AraG	Chemical	C104457
+20528871	927	936	etoposide	Chemical	D005047
+20528871	941	957	cyclophosphamide	Chemical	D003520
+20528871	968	989	neurological toxicity	Disease	D009422
+20528871	CID	C104457	D009422
+20528871	CID	C104457	D006402
+20528871	CID	C104457	D059352
+
+11672959|t|The 3-week sulphasalazine syndrome strikes again.
+11672959|a|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.
+11672959	11	25	sulphasalazine	Chemical	D012460
+11672959	98	108	dermatitis	Disease	D003872
+11672959	110	115	fever	Disease	D005334
+11672959	117	132	lymphadenopathy	Disease	D008206
+11672959	137	146	hepatitis	Disease	D056486
+11672959	194	208	sulphasalazine	Chemical	D012460
+11672959	227	247	rheumatoid arthritis	Disease	D001172
+11672959	333	346	lymphadenitis	Disease	D008199
+11672959	473	494	adverse drug reaction	Disease	D064420
+11672959	519	541	drug-induced hepatitis	Disease	D056486
+11672959	634	646	autoimmunity	Disease	D001327
+11672959	668	687	multi-organ failure	Disease	D009102
+11672959	692	698	sepsis	Disease	D018805
+11672959	833	864	massive hepatocellular necrosis	Disease	D047508
+11672959	889	900	myocarditis	Disease	D009205
+11672959	934	943	nephritis	Disease	D009393
+11672959	958	978	bone marrow necrosis	Disease	D001855
+11672959	1000	1010	malignancy	Disease	D009369
+11672959	1137	1151	sulphasalazine	Chemical	D012460
+11672959	1215	1229	sulphasalazine	Chemical	D012460
+11672959	CID	D012460	D005334
+11672959	CID	D012460	D009205
+11672959	CID	D012460	D008206
+11672959	CID	D012460	D018805
+11672959	CID	D012460	D009393
+11672959	CID	D012460	D003872
+11672959	CID	D012460	D056486
+
+11928786|t|Bupropion (Zyban) toxicity.
+11928786|a|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.
+11928786	0	9	Bupropion	Chemical	D016642
+11928786	11	16	Zyban	Chemical	D016642
+11928786	18	26	toxicity	Disease	D064420
+11928786	28	37	Bupropion	Chemical	D016642
+11928786	54	68	antidepressant	Chemical	D000928
+11928786	93	104	amphetamine	Chemical	D000661
+11928786	106	111	Zyban	Chemical	D016642
+11928786	148	171	bupropion hydrochloride	Chemical	D016642
+11928786	287	295	overdose	Disease	D062787
+11928786	398	406	toxicity	Disease	D064420
+11928786	433	444	tachycardia	Disease	D013610
+11928786	458	472	hallucinations	Disease	D006212
+11928786	477	488	convulsions	Disease	D012640
+11928786	520	539	cardiac arrhythmias	Disease	D001145
+11928786	596	610	cardiac arrest	Disease	D006323
+11928786	818	827	bupropion	Chemical	D016642
+11928786	839	847	seizures	Disease	D012640
+11928786	866	874	diazepam	Chemical	D003975
+11928786	893	904	tachycardia	Disease	D013610
+11928786	935	944	adenosine	Chemical	D000241
+11928786	946	951	Zyban	Chemical	D016642
+11928786	971	1011	neurological and cardiovascular toxicity	Disease	D020258|D002318	neurological toxicity|cardiovascular toxicity
+11928786	1015	1023	overdose	Disease	D062787
+11928786	CID	D016642	D013610
+11928786	CID	D016642	D012640
+11928786	CID	D016642	D006212
+11928786	CID	D016642	D001145
+11928786	CID	D016642	D006323
+
+7977601|t|Survey of complications of indocyanine green angiography in Japan.
+7977601|a|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.
+7977601	27	44	indocyanine green	Chemical	D007208
+7977601	103	120	indocyanine green	Chemical	D007208
+7977601	213	230	indocyanine green	Chemical	D007208
+7977601	360	377	indocyanine green	Chemical	D007208
+7977601	476	493	indocyanine green	Chemical	D007208
+7977601	618	635	indocyanine green	Chemical	D007208
+7977601	821	838	indocyanine green	Chemical	D007208
+7977601	1008	1014	nausea	Disease	D009325
+7977601	1016	1025	exanthema	Disease	D005076
+7977601	1027	1037	urtication	Disease	D014581
+7977601	1039	1048	itchiness	Disease	D011537
+7977601	1137	1141	pain	Disease	D010146
+7977601	1198	1209	hypotension	Disease	D007022
+7977601	1219	1230	hypotensive	Disease	D007022
+7977601	1263	1268	shock	Disease	D012769
+7977601	1333	1350	indocyanine green	Chemical	D007208
+7977601	1411	1429	fluorescein sodium	Chemical	D019793
+7977601	1445	1462	indocyanine green	Chemical	D007208
+7977601	1476	1487	fluorescein	Chemical	D019793
+7977601	CID	D007208	D012769
+7977601	CID	D007208	D010146
+7977601	CID	D007208	D007022
+7977601	CID	D007208	D011537
+7977601	CID	D007208	D009325
+7977601	CID	D007208	D005076
+7977601	CID	D007208	D014581
+
+19300402|t|Bradykinin receptors antagonists and nitric oxide synthase inhibitors in vincristine and streptozotocin induced hyperalgesia in chemotherapy and diabetic neuropathy rat model.
+19300402|a|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.
+19300402	0	10	Bradykinin	Chemical	D001920
+19300402	37	49	nitric oxide	Chemical	D009569
+19300402	73	84	vincristine	Chemical	D014750
+19300402	89	103	streptozotocin	Chemical	D013311
+19300402	112	124	hyperalgesia	Disease	D006930
+19300402	145	164	diabetic neuropathy	Disease	D003929
+19300402	244	246	NO	Chemical	D009569
+19300402	327	329	NO	Chemical	D009569
+19300402	409	411	NO	Chemical	D009569
+19300402	549	559	bradykinin	Chemical	D001920
+19300402	561	568	HOE 140	Chemical	C065679
+19300402	588	605	des Arg10 HOE 140	Chemical	C078665
+19300402	648	724	diabetic (streptozotocin-induced) and toxic (vincristine-induced) neuropathy	Disease	D003929|D010523	diabetic (streptozotocin-induced) neuropathy|toxic (vincristine-induced) neuropathy
+19300402	767	771	pain	Disease	D010146
+19300402	969	979	bradykinin	Chemical	D001920
+19300402	1004	1006	NO	Chemical	D009569
+19300402	1033	1035	NO	Chemical	D009569
+19300402	1062	1083	diabetic hyperalgesia	Disease	D006930
+19300402	1190	1197	HOE 140	Chemical	C065679
+19300402	1202	1219	des Arg10 HOE 140	Chemical	C078665
+19300402	1271	1273	NO	Chemical	D009569
+19300402	1296	1298	NO	Chemical	D009569
+19300402	1330	1340	bradykinin	Chemical	D001920
+19300402	1357	1369	hyperalgesia	Disease	D006930
+19300402	1382	1393	vincristine	Chemical	D014750
+19300402	1475	1482	HOE 140	Chemical	C065679
+19300402	1486	1502	des-Arg10HOE 140	Chemical	C078665
+19300402	1506	1522	toxic neuropathy	Disease	D010523
+19300402	1654	1683	diabetic and toxic neuropathy	Disease	D003929|D010523	diabetic neuropathy|toxic neuropathy
+19300402	1688	1702	streptozotocin	Chemical	D013311
+19300402	1711	1723	hyperalgesia	Disease	D006930
+19300402	1735	1737	NO	Chemical	D009569
+19300402	1790	1800	bradykinin	Chemical	D001920
+19300402	1813	1824	vincristine	Chemical	D014750
+19300402	1833	1845	hyperalgesia	Disease	D006930
+19300402	1846	1856	bradykinin	Chemical	D001920
+19300402	1885	1887	NO	Chemical	D009569
+19300402	1962	1972	bradykinin	Chemical	D001920
+19300402	1998	2000	NO	Chemical	D009569
+19300402	2056	2072	neuropathic pain	Disease	D009437
+19300402	CID	D013311	D003929
+19300402	CID	D013311	D006930
+19300402	CID	D014750	D010523
+19300402	CID	D014750	D006930
+
+15325671|t|Cardiac toxicity observed in association with high-dose cyclophosphamide-based chemotherapy for metastatic breast cancer.
+15325671|a|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.
+15325671	0	16	Cardiac toxicity	Disease	D066126
+15325671	56	72	cyclophosphamide	Chemical	D003520
+15325671	107	120	breast cancer	Disease	D001943
+15325671	136	152	Cyclophosphamide	Chemical	D003520
+15325671	289	297	toxicity	Disease	D064420
+15325671	301	315	cardiomyopathy	Disease	D009202
+15325671	343	353	paclitaxel	Chemical	D017239
+15325671	355	364	melphalan	Chemical	D008558
+15325671	379	395	cyclophosphamide	Chemical	D003520
+15325671	397	405	thiotepa	Chemical	D013852
+15325671	411	422	carboplatin	Chemical	D016190
+15325671	493	506	breast cancer	Disease	D001943
+15325671	583	596	breast cancer	Disease	D001943
+15325671	623	639	cyclophosphamide	Chemical	D003520
+15325671	746	770	congestive heart failure	Disease	D006333
+15325671	772	775	CHF	Disease	D006333
+15325671	881	893	hypertension	Disease	D006973
+15325671	927	944	diabetes mellitus	Disease	D003920
+15325671	959	973	anthracyclines	Chemical	D018943
+15325671	1080	1083	CHF	Disease	D006333
+15325671	1105	1121	cyclophosphamide	Chemical	D003520
+15325671	1204	1220	cyclophosphamide	Chemical	D003520
+15325671	1229	1245	cardiac toxicity	Disease	D066126
+15325671	1347	1350	CHF	Disease	D006333
+15325671	1430	1433	CHF	Disease	D006333
+15325671	1683	1699	cyclophosphamide	Chemical	D003520
+15325671	1716	1719	CHF	Disease	D006333
+15325671	CID	D003520	D006333
+
+9746003|t|Inappropriate use of carbamazepine and vigabatrin in typical absence seizures.
+9746003|a|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.
+9746003	21	34	carbamazepine	Chemical	D002220
+9746003	39	49	vigabatrin	Chemical	D020888
+9746003	61	77	absence seizures	Disease	D004832
+9746003	79	92	Carbamazepine	Chemical	D002220
+9746003	97	107	vigabatrin	Chemical	D020888
+9746003	139	155	absence seizures	Disease	D004832
+9746003	271	284	carbamazepine	Chemical	D002220
+9746003	324	334	Vigabatrin	Chemical	D020888
+9746003	445	458	carbamazepine	Chemical	D002220
+9746003	486	501	myoclonic jerks	Disease	D009207
+9746003	535	548	carbamazepine	Chemical	D002220
+9746003	595	605	vigabatrin	Chemical	D020888
+9746003	694	710	sodium valproate	Chemical	D014635
+9746003	712	723	lamotrigine	Chemical	C047781
+9746003	728	740	ethosuximide	Chemical	D005013
+9746003	CID	D002220	D004832
+9746003	CID	D002220	D009207
+9746003	CID	D020888	D004832
+
+1992636|t|Hemolytic anemia associated with the use of omeprazole.
+1992636|a|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.
+1992636	0	16	Hemolytic anemia	Disease	D000743
+1992636	44	54	omeprazole	Chemical	D009853
+1992636	56	66	Omeprazole	Chemical	D009853
+1992636	238	258	peptic ulcer disease	Disease	D010437
+1992636	260	278	reflux esophagitis	Disease	D005764
+1992636	288	314	Zollinger-Ellison syndrome	Disease	D015043
+1992636	350	360	omeprazole	Chemical	D009853
+1992636	538	548	omeprazole	Chemical	D009853
+1992636	550	566	hemolytic anemia	Disease	D000743
+1992636	600	608	lethargy	Disease	D053609
+1992636	614	633	shortness of breath	Disease	D004417
+1992636	669	679	omeprazole	Chemical	D009853
+1992636	854	863	bilirubin	Chemical	D001663
+1992636	892	902	omeprazole	Chemical	D009853
+1992636	987	997	omeprazole	Chemical	D009853
+1992636	1019	1035	hemolytic anemia	Disease	D000743
+1992636	CID	D009853	D004417
+1992636	CID	D009853	D000743
+1992636	CID	D009853	D053609
+
+8387218|t|The use and toxicity of didanosine (ddI) in HIV antibody-positive individuals intolerant to zidovudine (AZT)
+8387218|a|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.
+8387218	12	20	toxicity	Disease	D064420
+8387218	24	34	didanosine	Chemical	D016049
+8387218	36	39	ddI	Chemical	D016049
+8387218	44	65	HIV antibody-positive	Disease	D015658
+8387218	92	102	zidovudine	Chemical	D015215
+8387218	104	107	AZT	Chemical	D015215
+8387218	158	168	zidovudine	Chemical	D015215
+8387218	170	173	AZT	Chemical	D015215
+8387218	184	194	didanosine	Chemical	D016049
+8387218	196	199	ddI	Chemical	D016049
+8387218	394	418	opportunistic infections	Disease	D009894
+8387218	457	461	AIDS	Disease	D000163
+8387218	547	551	AIDS	Disease	D000163
+8387218	1022	1032	didanosine	Chemical	D016049
+8387218	1078	1087	diarrhoea	Disease	D003967
+8387218	1147	1168	Peripheral neuropathy	Disease	D010523
+8387218	1197	1209	pancreatitis	Disease	D010195
+8387218	1277	1291	abdominal pain	Disease	D015746
+8387218	1318	1342	glucose tolerance curves	Disease	D018149
+8387218	1361	1369	diabetes	Disease	D003920
+8387218	1451	1461	didanosine	Chemical	D016049
+8387218	CID	D016049	D018149
+8387218	CID	D016049	D010523
+8387218	CID	D016049	D003967
+8387218	CID	D016049	D010195
+
+20698227|t|Can angiogenesis be a target of treatment for ribavirin associated hemolytic anemia?
+20698227|a|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.
+20698227	46	55	ribavirin	Chemical	D012254
+20698227	67	83	hemolytic anemia	Disease	D000743
+20698227	111	120	ribavirin	Chemical	D012254
+20698227	208	217	sunitinib	Chemical	C473478
+20698227	222	231	sorafenib	Chemical	C471405
+20698227	263	272	hemolysis	Disease	D006461
+20698227	458	464	anemia	Disease	D000740
+20698227	493	536	chronically infected with hepatitis C virus	Disease	D019698
+20698227	553	582	pegylated interferon alpha 2a	Chemical	C100416
+20698227	587	596	ribavirin	Chemical	D012254
+20698227	1024	1044	pegylated interferon	Chemical	C417083
+20698227	1049	1058	ribavirin	Chemical	D012254
+20698227	1279	1288	ribavirin	Chemical	D012254
+20698227	1297	1303	anemia	Disease	D000740
+20698227	1321	1332	hepatitis C	Disease	D019698
+20698227	1489	1498	ribavirin	Chemical	D012254
+20698227	CID	C471405	D006461
+20698227	CID	C473478	D006461
+
+20477932|t|Cocaine causes memory and learning impairments in rats: involvement of nuclear factor kappa B and oxidative stress, and prevention by topiramate.
+20477932|a|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.
+20477932	0	7	Cocaine	Chemical	D003042
+20477932	15	46	memory and learning impairments	Disease	D008569|D007859	memory impairments|learning impairments
+20477932	134	144	topiramate	Chemical	C052342
+20477932	191	198	cocaine	Chemical	D003042
+20477932	199	207	toxicity	Disease	D064420
+20477932	312	319	cocaine	Chemical	D003042
+20477932	494	502	toxicity	Disease	D064420
+20477932	585	597	nitric oxide	Chemical	D009569
+20477932	677	687	topiramate	Chemical	C052342
+20477932	723	740	cocaine addiction	Disease	D019970
+20477932	785	792	cocaine	Chemical	D003042
+20477932	874	881	cocaine	Chemical	D003042
+20477932	907	910	GSH	Chemical	D005978
+20477932	929	940	glutathione	Chemical	D005978
+20477932	1087	1094	cocaine	Chemical	D003042
+20477932	1313	1324	glutathione	Chemical	D005978
+20477932	1479	1486	cocaine	Chemical	D003042
+20477932	1488	1498	Topiramate	Chemical	C052342
+20477932	CID	D003042	D007859
+20477932	CID	D003042	D008569
+
+9495837|t|Antinociceptive and antiamnesic properties of the presynaptic cholinergic amplifier PG-9.
+9495837|a|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.
+9495837	84	88	PG-9	Chemical	C087567
+9495837	120	162	3 alpha-tropyl 2-(p-bromophenyl)propionate	Chemical	C087567
+9495837	170	174	PG-9	Chemical	C087567
+9495837	401	405	PG-9	Chemical	C087567
+9495837	518	522	PG-9	Chemical	C087567
+9495837	578	586	atropine	Chemical	D001285
+9495837	617	628	pirenzepine	Chemical	D010890
+9495837	633	644	dicyclomine	Chemical	D004025
+9495837	653	666	acetylcholine	Chemical	D000109
+9495837	676	691	hemicholinium-3	Chemical	D006426
+9495837	726	734	naloxone	Chemical	D009270
+9495837	740	764	gamma-aminobutyric acidB	Chemical	D005680
+9495837	776	821	3-aminopropyl-diethoxy-methyl-phosphinic acid	Chemical	C066430
+9495837	838	863	R-(alpha)-methylhistamine	Chemical	C069357
+9495837	883	893	quinpirole	Chemical	D019257
+9495837	899	919	5-hydroxytryptamine4	Chemical	D012701
+9495837	931	997	2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester	Chemical	C072790
+9495837	1017	1037	5-hydroxytryptamin1A	Chemical	D012701
+9495837	1049	1105	1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine	Chemical	C058895
+9495837	1147	1156	reserpine	Chemical	D012110
+9495837	1211	1215	PG-9	Chemical	C087567
+9495837	1320	1324	PG-9	Chemical	C087567
+9495837	1366	1373	amnesia	Disease	D000647
+9495837	1385	1396	scopolamine	Chemical	D012601
+9495837	1418	1429	dicyclomine	Chemical	D004025
+9495837	1511	1515	PG-9	Chemical	C087567
+9495837	1820	1827	amnesic	Disease	D000647
+9495837	1852	1856	PG-9	Chemical	C087567
+9495837	1880	1893	acetylcholine	Chemical	D000109
+9495837	1973	1977	PG-9	Chemical	C087567
+9495837	CID	D012601	D000647
+9495837	CID	D004025	D000647
+
+1468485|t|Hyperbaric oxygen therapy for control of intractable cyclophosphamide-induced hemorrhagic cystitis.
+1468485|a|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.
+1468485	11	17	oxygen	Chemical	D010100
+1468485	53	69	cyclophosphamide	Chemical	D003520
+1468485	78	98	hemorrhagic cystitis	Disease	D006470|D003556	hemorrhagic|cystitis
+1468485	132	152	hemorrhagic cystitis	Disease	D006470|D003556	hemorrhagic|cystitis
+1468485	160	176	cyclophosphamide	Chemical	D003520
+1468485	189	213	Wegener's granulomatosis	Disease	D014890
+1468485	314	336	prostaglandin F2 alpha	Chemical	D015237
+1468485	364	374	hemorrhage	Disease	D006470
+1468485	400	406	oxygen	Chemical	D010100
+1468485	484	492	bleeding	Disease	D006470
+1468485	568	577	hematuria	Disease	D006417
+1468485	726	742	cyclophosphamide	Chemical	D003520
+1468485	751	771	hemorrhagic cystitis	Disease	D006470|D003556	hemorrhagic|cystitis
+1468485	CID	D003520	D006417
+1468485	CID	D003520	D003556
+1468485	CID	D003520	D006470
+
+1009330|t|Further studies on effects of irrigation solutions on rat bladders.
+1009330|a|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.
+1009330	226	242	p-choloroaniline	Chemical	C004658
+1009330	274	299	chlorhexidine-digluconate	Chemical	C010882
+1009330	319	327	cystitis	Disease	D003556
+1009330	350	359	kanamycin	Chemical	D007612
+1009330	360	368	colistin	Chemical	D003091
+1009330	373	388	povidone-iodine	Chemical	D011206
+1009330	430	438	cystitis	Disease	D003556
+1009330	495	506	Picloxydine	Chemical	C005253
+1009330	565	573	cystitis	Disease	D003556
+1009330	CID	C010882	D003556
+1009330	CID	D003091	D003556
+1009330	CID	D007612	D003556
+1009330	CID	D011206	D003556
+
+347884|t|Clinical experiences in an open and a double-blind trial.
+347884|a|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.
+347884	101	112	bromperidol	Chemical	C006820
+347884	201	212	haloperidol	Chemical	D006220
+347884	665	700	extrapyramidal concomitant symptoms	Disease	D001480
+347884	929	940	haloperidol	Chemical	D006220
+347884	1012	1082	psychotic syndromes belonging predominantly to the schizophrenia group	Disease	D019967
+347884	1174	1185	bromperidol	Chemical	C006820
+347884	CID	D006220	D001480
+347884	CID	C006820	D001480
+
+20667451|t|Curcumin ameliorates cognitive dysfunction and oxidative damage in phenobarbitone and carbamazepine administered rats.
+20667451|a|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.
+20667451	0	8	Curcumin	Chemical	D003474
+20667451	21	42	cognitive dysfunction	Disease	D003072
+20667451	67	81	phenobarbitone	Chemical	D010634
+20667451	86	99	carbamazepine	Chemical	D002220
+20667451	144	158	phenobarbitone	Chemical	D010634
+20667451	163	176	carbamazepine	Chemical	D002220
+20667451	201	221	cognitive impairment	Disease	D003072
+20667451	336	356	cognitive impairment	Disease	D003072
+20667451	381	389	Curcumin	Chemical	D003474
+20667451	546	554	curcumin	Chemical	D003474
+20667451	573	587	phenobarbitone	Chemical	D010634
+20667451	593	606	carbamazepine	Chemical	D002220
+20667451	615	635	cognitive impairment	Disease	D003072
+20667451	698	706	curcumin	Chemical	D003474
+20667451	712	726	phenobarbitone	Chemical	D010634
+20667451	731	744	carbamazepine	Chemical	D002220
+20667451	963	977	phenobarbitone	Chemical	D010634
+20667451	982	995	carbamazepine	Chemical	D002220
+20667451	1009	1024	malondialdehyde	Chemical	D008315
+20667451	1037	1048	glutathione	Chemical	D005978
+20667451	1094	1108	phenobarbitone	Chemical	D010634
+20667451	1113	1126	carbamazepine	Chemical	D002220
+20667451	1159	1192	impairment of learning and memory	Disease	D003072
+20667451	1247	1255	curcumin	Chemical	D003474
+20667451	1285	1305	cognitive impairment	Disease	D003072
+20667451	1389	1397	Curcumin	Chemical	D003474
+20667451	1493	1507	phenobarbitone	Chemical	D010634
+20667451	1519	1532	carbamazepine	Chemical	D002220
+20667451	1558	1566	curcumin	Chemical	D003474
+20667451	1607	1643	deterioration of cognitive functions	Disease	D003072
+20667451	1686	1700	phenobarbitone	Chemical	D010634
+20667451	1705	1718	carbamazepine	Chemical	D002220
+20667451	1804	1812	curcumin	Chemical	D003474
+20667451	1877	1891	phenobarbitone	Chemical	D010634
+20667451	1896	1909	carbamazepine	Chemical	D002220
+20667451	1932	1952	cognitive impairment	Disease	D003072
+20667451	CID	D010634	D003072
+20667451	CID	D002220	D003072
+
+19767176|t|Pyrrolidine dithiocarbamate protects the piriform cortex in the pilocarpine status epilepticus model.
+19767176|a|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.
+19767176	0	27	Pyrrolidine dithiocarbamate	Chemical	C020972
+19767176	64	75	pilocarpine	Chemical	D010862
+19767176	76	94	status epilepticus	Disease	D013226
+19767176	102	129	Pyrrolidine dithiocarbamate	Chemical	C020972
+19767176	131	135	PDTC	Chemical	C020972
+19767176	272	278	oxygen	Chemical	D010100
+19767176	353	368	neuronal damage	Disease	D009410
+19767176	467	471	PDTC	Chemical	C020972
+19767176	475	493	status epilepticus	Disease	D013226
+19767176	592	603	pilocarpine	Chemical	D010862
+19767176	636	640	PDTC	Chemical	C020972
+19767176	662	680	status epilepticus	Disease	D013226
+19767176	760	764	PDTC	Chemical	C020972
+19767176	828	846	status epilepticus	Disease	D013226
+19767176	895	913	status epilepticus	Disease	D013226
+19767176	932	947	neuronal damage	Disease	D009410
+19767176	1030	1034	PDTC	Chemical	C020972
+19767176	1219	1223	PDTC	Chemical	C020972
+19767176	1247	1265	status epilepticus	Disease	D013226
+19767176	1322	1326	PDTC	Chemical	C020972
+19767176	1390	1403	neuronal loss	Disease	D009410
+19767176	1463	1469	oxygen	Chemical	D010100
+19767176	1535	1542	seizure	Disease	D012640
+19767176	1554	1569	neuronal damage	Disease	D009410
+19767176	1731	1735	PDTC	Chemical	C020972
+19767176	CID	D010862	D013226
+19767176	CID	D010862	D009410
+
+16330293|t|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.
+16330293|a|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.
+16330293	20	28	nicotine	Chemical	D009538
+16330293	59	67	nicotine	Chemical	D009538
+16330293	178	186	Nicotine	Chemical	D009538
+16330293	231	239	nicotine	Chemical	D009538
+16330293	274	282	nicotine	Chemical	D009538
+16330293	313	321	nicotine	Chemical	D009538
+16330293	505	513	nicotine	Chemical	D009538
+16330293	531	539	nicotine	Chemical	D009538
+16330293	680	693	heart disease	Disease	D006331
+16330293	695	707	hypertension	Disease	D006973
+16330293	745	762	diabetes mellitus	Disease	D003920
+16330293	824	832	nicotine	Chemical	D009538
+16330293	849	857	nicotine	Chemical	D009538
+16330293	1460	1468	nicotine	Chemical	D009538
+16330293	1481	1489	nicotine	Chemical	D009538
+16330293	1541	1549	nicotine	Chemical	D009538
+16330293	2051	2057	nausea	Disease	D009325
+16330293	2098	2105	hiccups	Disease	D006606
+16330293	2148	2156	headache	Disease	D006261
+16330293	2545	2553	nicotine	Chemical	D009538
+16330293	2571	2579	nicotine	Chemical	D009538
+16330293	CID	D009538	D009325
+16330293	CID	D009538	D006261
+16330293	CID	D009538	D006606
+
+14568327|t|Development of levodopa-induced dyskinesias in parkinsonian monkeys may depend upon rate of symptom onset and/or duration of symptoms.
+14568327|a|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.
+14568327	15	23	levodopa	Chemical	D007980
+14568327	32	43	dyskinesias	Disease	D004409
+14568327	47	59	parkinsonian	Disease	D010300
+14568327	135	143	Levodopa	Chemical	D007980
+14568327	152	163	dyskinesias	Disease	D004409
+14568327	165	169	LIDs	Disease	D004409
+14568327	227	246	Parkinson's disease	Disease	D010300
+14568327	248	250	PD	Disease	D010300
+14568327	417	421	LIDs	Disease	D004409
+14568327	469	473	MPTP	Chemical	D015632
+14568327	482	494	parkinsonism	Disease	D010302
+14568327	623	631	levodopa	Chemical	D007980
+14568327	678	682	LIDs	Disease	D004409
+14568327	716	720	MPTP	Chemical	D015632
+14568327	801	809	levodopa	Chemical	D007980
+14568327	828	838	dyskinesia	Disease	D004409
+14568327	871	879	levodopa	Chemical	D007980
+14568327	932	936	MPTP	Chemical	D015632
+14568327	1024	1032	levodopa	Chemical	D007980
+14568327	1075	1079	LIDs	Disease	D004409
+14568327	1087	1097	dyskinesia	Disease	D004409
+14568327	1143	1151	levodopa	Chemical	D007980
+14568327	1224	1232	levodopa	Chemical	D007980
+14568327	1363	1367	LIDs	Disease	D004409
+14568327	1453	1461	levodopa	Chemical	D007980
+14568327	1548	1552	LIDs	Disease	D004409
+14568327	CID	D007980	D004409
+14568327	CID	D015632	D010302
+
+11250767|t|Propylthiouracil-induced perinuclear-staining antineutrophil cytoplasmic autoantibody-positive vasculitis in conjunction with pericarditis.
+11250767|a|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.
+11250767	0	16	Propylthiouracil	Chemical	D011441
+11250767	95	105	vasculitis	Disease	D014657
+11250767	126	138	pericarditis	Disease	D010493
+11250767	173	189	propylthiouracil	Chemical	D011441
+11250767	198	208	vasculitis	Disease	D014657
+11250767	226	238	pericarditis	Disease	D010493
+11250767	298	313	hyperthyroidism	Disease	D006980
+11250767	327	343	propylthiouracil	Chemical	D011441
+11250767	366	378	pericarditis	Disease	D010493
+11250767	380	385	fever	Disease	D005334
+11250767	391	409	glomerulonephritis	Disease	D005921
+11250767	548	563	Graves' disease	Disease	D006111
+11250767	570	585	febrile illness	Disease	D005334
+11250767	602	614	pericarditis	Disease	D010493
+11250767	795	811	Propylthiouracil	Chemical	D011441
+11250767	880	890	prednisone	Chemical	D011241
+11250767	972	984	pericarditis	Disease	D010493
+11250767	1012	1022	vasculitis	Disease	D014657
+11250767	1039	1057	propylthio- uracil	Chemical	D011441
+11250767	1079	1091	Pericarditis	Disease	D010493
+11250767	1141	1151	vasculitis	Disease	D014657
+11250767	1168	1186	propylthio- uracil	Chemical	D011441
+11250767	CID	D011441	D005334
+11250767	CID	D011441	D010493
+11250767	CID	D011441	D005921
+
+11206082|t|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.
+11206082|a|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.
+11206082	59	73	beta-carboline	Chemical	C036150
+11206082	82	90	seizures	Disease	D012640
+11206082	169	173	GABA	Chemical	D005680
+11206082	301	309	seizures	Disease	D012640
+11206082	348	383	methyl beta-carboline-3-carboxylate	Chemical	C036150
+11206082	385	393	beta-CCM	Chemical	C036150
+11206082	422	426	GABA	Chemical	D005680
+11206082	439	453	benzodiazepine	Chemical	D001569
+11206082	571	575	GABA	Chemical	D005680
+11206082	601	609	diazepam	Chemical	D003975
+11206082	663	671	diazepam	Chemical	D003975
+11206082	728	738	picrotoxin	Chemical	D010852
+11206082	744	761	pentylenetetrazol	Chemical	D010433
+11206082	770	778	seizures	Disease	D012640
+11206082	888	896	beta-CCM	Chemical	C036150
+11206082	916	924	diazepam	Chemical	D003975
+11206082	926	936	picrotoxin	Chemical	D010852
+11206082	942	959	pentylenetetrazol	Chemical	D010433
+11206082	1058	1062	GABA	Chemical	D005680
+11206082	CID	D010852	D012640
+11206082	CID	D010433	D012640
+11206082	CID	C036150	D012640
+
+11027905|t|Analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized, controlled, double-blind, crossover, double-dose study.
+11027905|a|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.
+11027905	32	40	ketamine	Chemical	D007649
+11027905	44	50	cancer	Disease	D009369
+11027905	63	71	morphine	Chemical	D009020
+11027905	151	155	Pain	Disease	D010146
+11027905	174	182	morphine	Chemical	D009020
+11027905	253	273	N-methyl-D-aspartate	Chemical	D016202
+11027905	275	279	NMDA	Chemical	D016202
+11027905	302	310	ketamine	Chemical	D007649
+11027905	372	376	pain	Disease	D010146
+11027905	396	412	neuropathic pain	Disease	D009437
+11027905	451	459	ketamine	Chemical	D007649
+11027905	503	509	cancer	Disease	D009369
+11027905	525	529	pain	Disease	D010146
+11027905	548	556	morphine	Chemical	D009020
+11027905	618	622	Pain	Disease	D010146
+11027905	663	669	nausea	Disease	D009325
+11027905	674	682	vomiting	Disease	D014839
+11027905	696	705	confusion	Disease	D003221
+11027905	711	720	dry mouth	Disease	D014987
+11027905	991	999	Ketamine	Chemical	D007649
+11027905	1052	1056	pain	Disease	D010146
+11027905	1178	1192	Hallucinations	Disease	D006212
+11027905	1345	1353	diazepam	Chemical	D003975
+11027905	1449	1457	ketamine	Chemical	D007649
+11027905	1499	1507	ketamine	Chemical	D007649
+11027905	1612	1620	ketamine	Chemical	D007649
+11027905	1622	1630	Ketamine	Chemical	D007649
+11027905	1643	1651	morphine	Chemical	D009020
+11027905	1675	1679	pain	Disease	D010146
+11027905	1699	1715	neuropathic pain	Disease	D009437
+11027905	1892	1900	ketamine	Chemical	D007649
+11027905	CID	D007649	D006212
+
+9334596|t|Endocrine screening in 1,022 men with erectile dysfunction: clinical significance and cost-effective strategy.
+9334596|a|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.
+9334596	38	58	erectile dysfunction	Disease	D007172
+9334596	153	165	testosterone	Chemical	D013739
+9334596	232	252	erectile dysfunction	Disease	D007172
+9334596	535	547	Testosterone	Chemical	D013739
+9334596	630	642	testosterone	Chemical	D013739
+9334596	695	712	low sexual desire	Disease	D020018
+9334596	714	726	gynecomastia	Disease	D006177
+9334596	730	742	testosterone	Chemical	D013739
+9334596	921	941	erectile dysfunction	Disease	D007172
+9334596	1063	1080	low sexual desire	Disease	D020018
+9334596	1099	1111	gynecomastia	Disease	D006177
+9334596	1144	1166	testosterone heptylate	Chemical	C004648
+9334596	1203	1215	hypogonadism	Disease	D007006
+9334596	1220	1233	bromocriptine	Chemical	D001971
+9334596	1238	1256	hyperprolactinemia	Disease	D006966
+9334596	1267	1279	Testosterone	Chemical	D013739
+9334596	1396	1408	testosterone	Chemical	D013739
+9334596	1483	1499	pituitary tumors	Disease	D010911
+9334596	1522	1534	testosterone	Chemical	D013739
+9334596	1572	1584	testosterone	Chemical	D013739
+9334596	1625	1649	hypothalamic dysfunction	Disease	D007027
+9334596	1741	1761	erectile dysfunction	Disease	D007172
+9334596	1937	1949	testosterone	Chemical	D013739
+9334596	1967	1984	low sexual desire	Disease	D020018
+9334596	2062	2074	testosterone	Chemical	D013739
+9334596	2233	2245	prolactinoma	Disease	D015175
+9334596	2400	2413	prolactinomas	Disease	D015175
+9334596	2428	2441	Bromocriptine	Chemical	D001971
+9334596	2598	2610	Testosterone	Chemical	D013739
+9334596	2732	2744	testosterone	Chemical	D013739
+9334596	2767	2787	erectile dysfunction	Disease	D007172
+9334596	2962	2978	pituitary tumors	Disease	D010911
+9334596	3021	3033	testosterone	Chemical	D013739
+9334596	3065	3082	low sexual desire	Disease	D020018
+9334596	3221	3238	low sexual desire	Disease	D020018
+9334596	3240	3252	gynecomastia	Disease	D006177
+9334596	3260	3272	testosterone	Chemical	D013739
+9334596	CID	D013739	D020018
+
+8595686|t|Thiopentone pretreatment for propofol injection pain in ambulatory patients.
+8595686|a|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.
+8595686	0	11	Thiopentone	Chemical	D013874
+8595686	29	37	propofol	Chemical	D015742
+8595686	48	52	pain	Disease	D010146
+8595686	101	109	propofol	Chemical	D015742
+8595686	120	124	pain	Disease	D010146
+8595686	307	315	propofol	Chemical	D015742
+8595686	381	390	lidocaine	Chemical	D008012
+8595686	420	431	thiopentone	Chemical	D013874
+8595686	538	546	propofol	Chemical	D015742
+8595686	620	641	Loss of consciousness	Disease	D014474
+8595686	983	987	pain	Disease	D010146
+8595686	1257	1265	propofol	Chemical	D015742
+8595686	1302	1311	lidocaine	Chemical	D008012
+8595686	1350	1358	propofol	Chemical	D015742
+8595686	1369	1373	pain	Disease	D010146
+8595686	1405	1416	thiopentone	Chemical	D013874
+8595686	CID	D015742	D010146
+
+6466532|t|Comparison of i.v. glycopyrrolate and atropine in the prevention of bradycardia and arrhythmias following repeated doses of suxamethonium in children.
+6466532|a|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.
+6466532	19	33	glycopyrrolate	Chemical	D006024
+6466532	38	46	atropine	Chemical	D001285
+6466532	68	79	bradycardia	Disease	D001919
+6466532	84	95	arrhythmias	Disease	D001145
+6466532	124	137	suxamethonium	Chemical	D013390
+6466532	190	204	glycopyrrolate	Chemical	D006024
+6466532	234	242	atropine	Chemical	D001285
+6466532	334	344	arrhythmia	Disease	D001145
+6466532	349	360	bradycardia	Disease	D001919
+6466532	389	402	suxamethonium	Chemical	D013390
+6466532	502	516	glycopyrrolate	Chemical	D006024
+6466532	521	529	atropine	Chemical	D001285
+6466532	546	557	bradycardia	Disease	D001919
+6466532	680	691	Bradycardia	Disease	D001919
+6466532	854	868	glycopyrrolate	Chemical	D006024
+6466532	891	899	atropine	Chemical	D001285
+6466532	1024	1037	suxamethonium	Chemical	D013390
+6466532	CID	D013390	D001919
+
+6308277|t|Reduction in caffeine toxicity by acetaminophen.
+6308277|a|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.
+6308277	13	21	caffeine	Chemical	D002110
+6308277	22	30	toxicity	Disease	D064420
+6308277	34	47	acetaminophen	Chemical	D000082
+6308277	138	161	sodium acetylsalicylate	Chemical	-1
+6308277	163	171	caffeine	Chemical	D002110
+6308277	177	190	acetaminophen	Chemical	D000082
+6308277	274	282	caffeine	Chemical	D002110
+6308277	377	385	caffeine	Chemical	D002110
+6308277	460	473	acetaminophen	Chemical	D000082
+6308277	509	517	toxicity	Disease	D064420
+6308277	521	529	caffeine	Chemical	D002110
+6308277	588	601	acetaminophen	Chemical	D000082
+6308277	667	675	caffeine	Chemical	D002110
+6308277	721	732	convulsions	Disease	D012640
+6308277	784	797	acetaminophen	Chemical	D000082
+6308277	845	853	seizures	Disease	D012640
+6308277	882	890	caffeine	Chemical	D002110
+6308277	945	953	seizures	Disease	D012640
+6308277	977	985	caffeine	Chemical	D002110
+6308277	1015	1028	acetaminophen	Chemical	D000082
+6308277	1048	1056	caffeine	Chemical	D002110
+6308277	1058	1071	acetaminophen	Chemical	D000082
+6308277	1109	1117	seizures	Disease	D012640
+6308277	1191	1208	pentylenetetrezol	Chemical	D010433
+6308277	1286	1299	Acetaminophen	Chemical	D000082
+6308277	1374	1383	adenosine	Chemical	D000241
+6308277	1389	1392	ATP	Chemical	D000255
+6308277	1455	1468	acetaminophen	Chemical	D000082
+6308277	1496	1504	caffeine	Chemical	D002110
+6308277	CID	D002110	D012640
+6308277	CID	D010433	D012640
+
+2870085|t|Flestolol: an ultra-short-acting beta-adrenergic blocking agent.
+2870085|a|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.
+2870085	0	9	Flestolol	Chemical	C047847
+2870085	65	74	Flestolol	Chemical	C047847
+2870085	76	84	ACC-9089	Chemical	C047847
+2870085	217	226	Flestolol	Chemical	C047847
+2870085	446	455	flestolol	Chemical	C047847
+2870085	555	564	Flestolol	Chemical	C047847
+2870085	686	695	flestolol	Chemical	C047847
+2870085	726	735	Flestolol	Chemical	C047847
+2870085	777	790	isoproterenol	Chemical	D007545
+2870085	799	810	tachycardia	Disease	D013610
+2870085	858	867	flestolol	Chemical	C047847
+2870085	951	960	flestolol	Chemical	C047847
+2870085	1071	1080	Flestolol	Chemical	C047847
+2870085	1129	1161	supraventricular tachyarrhythmia	Disease	D013617
+2870085	1180	1195	unstable angina	Disease	D000789
+2870085	1197	1206	flestolol	Chemical	C047847
+2870085	1266	1276	chest pain	Disease	D002637
+2870085	1299	1308	flestolol	Chemical	C047847
+2870085	1396	1405	flestolol	Chemical	C047847
+2870085	CID	D007545	D013610
+
+1639466|t|Adverse effect of the calcium channel blocker nitrendipine on nephrosclerosis in rats with renovascular hypertension.
+1639466|a|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)
+1639466	22	29	calcium	Chemical	D002118
+1639466	46	58	nitrendipine	Chemical	D009568
+1639466	62	77	nephrosclerosis	Disease	D009400
+1639466	91	116	renovascular hypertension	Disease	D006978
+1639466	160	167	calcium	Chemical	D002118
+1639466	184	196	nitrendipine	Chemical	D009568
+1639466	204	215	angiotensin	Chemical	D000809
+1639466	244	253	enalapril	Chemical	D004656
+1639466	273	284	albuminuria	Disease	D000419
+1639466	392	417	renovascular hypertension	Disease	D006978
+1639466	465	477	hypertensive	Disease	D006973
+1639466	551	563	hypertensive	Disease	D006973
+1639466	582	591	enalapril	Chemical	D004656
+1639466	612	624	nitrendipine	Chemical	D009568
+1639466	936	945	Enalapril	Chemical	D004656
+1639466	954	966	nitrendipine	Chemical	D009568
+1639466	1157	1175	glomerulosclerosis	Disease	D005921
+1639466	1197	1206	enalapril	Chemical	D004656
+1639466	1238	1250	nitrendipine	Chemical	D009568
+1639466	1265	1276	albuminuria	Disease	D000419
+1639466	1372	1384	hypertensive	Disease	D006973
+1639466	1408	1426	glomerulosclerosis	Disease	D005921
+1639466	1468	1480	nitrendipine	Chemical	D009568
+1639466	1513	1525	hypertensive	Disease	D006973
+1639466	1619	1631	nitrendipine	Chemical	D009568
+1639466	1690	1699	enalapril	Chemical	D004656
+1639466	1759	1771	hypertensive	Disease	D006973
+1639466	CID	D009568	D000419
+1639466	CID	D009568	D009400
+
+1527456|t|Treatment of tinnitus by intratympanic instillation of lignocaine (lidocaine) 2 per cent through ventilation tubes.
+1527456|a|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.
+1527456	13	21	tinnitus	Disease	D014012
+1527456	55	65	lignocaine	Chemical	D008012
+1527456	67	76	lidocaine	Chemical	D008012
+1527456	116	146	Idiopathic subjective tinnitus	Disease	D014012
+1527456	148	151	IST	Disease	D014012
+1527456	248	251	IST	Disease	D014012
+1527456	285	295	lignocaine	Chemical	D008012
+1527456	297	306	lidocaine	Chemical	D008012
+1527456	409	417	tinnitus	Disease	D014012
+1527456	511	519	tinnitus	Disease	D014012
+1527456	600	608	tinnitus	Disease	D014012
+1527456	834	841	vertigo	Disease	D014717
+1527456	846	854	vomiting	Disease	D014839
+1527456	923	931	tinnitus	Disease	D014012
+1527456	CID	D008012	D014717
+1527456	CID	D008012	D014839
+
+220563|t|Perhexiline maleate and peripheral neuropathy.
+220563|a|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.
+220563	0	19	Perhexiline maleate	Chemical	C023470
+220563	24	45	peripheral neuropathy	Disease	D010523
+220563	47	68	Peripheral neuropathy	Disease	D010523
+220563	118	137	perhexiline maleate	Chemical	C023470
+220563	248	263	angina pectoris	Disease	D000787
+220563	407	429	demyelinating disorder	Disease	D003711
+220563	625	635	neuropathy	Disease	D009422
+220563	CID	C023470	D003711
+220563	CID	C023470	D010523
+
+137340|t|Effect of humoral modulators of morphine-induced increase in locomotor activity of mice.
+137340|a|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.
+137340	32	40	morphine	Chemical	D009020
+137340	49	79	increase in locomotor activity	Disease	D006948
+137340	129	137	morphine	Chemical	D009020
+137340	146	176	increase in locomotor activity	Disease	D006948
+137340	245	253	morphine	Chemical	D009020
+137340	276	306	increase in locomotor activity	Disease	D006948
+137340	320	328	morphine	Chemical	D009020
+137340	337	350	hyperactivity	Disease	D006948
+137340	370	381	scopolamine	Chemical	D012601
+137340	400	413	physostigmine	Chemical	D010830
+137340	433	448	methscopolamine	Chemical	D019832
+137340	453	464	neostigmine	Chemical	D009388
+137340	535	548	hyperactivity	Disease	D006948
+137340	561	569	morphine	Chemical	D009020
+137340	597	617	alpha-methyltyrosine	Chemical	D019805
+137340	661	669	tyrosine	Chemical	D014443
+137340	742	750	morphine	Chemical	D009020
+137340	789	810	p-chlorophenylalamine	Chemical	D010134
+137340	842	851	serotonin	Chemical	D012701
+137340	898	911	hyperactivity	Disease	D006948
+137340	972	980	morphine	Chemical	D009020
+137340	1012	1026	catecholamines	Chemical	D002395
+137340	1121	1129	morphine	Chemical	D009020
+137340	1163	1176	acetylcholine	Chemical	D000109
+137340	1300	1308	morphine	Chemical	D009020
+137340	1414	1422	morphine	Chemical	D009020
+137340	CID	D012601	D006948
+137340	CID	D009020	D006948
+
+9931093|t|Mechanisms of FK 506-induced hypertension in the rat.
+9931093|a|-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.
+9931093	14	20	FK 506	Chemical	D016559
+9931093	29	41	hypertension	Disease	D006973
+9931093	55	65	Tacrolimus	Chemical	D016559
+9931093	67	73	FK 506	Chemical	D016559
+9931093	145	151	FK 506	Chemical	D016559
+9931093	182	194	hypertension	Disease	D006973
+9931093	199	213	nephrotoxicity	Disease	D007674
+9931093	244	250	FK 506	Chemical	D016559
+9931093	259	271	hypertension	Disease	D006973
+9931093	307	313	FK 506	Chemical	D016559
+9931093	446	458	nitric oxide	Chemical	D009569
+9931093	657	666	FR 139317	Chemical	C079574
+9931093	670	676	FK 506	Chemical	D016559
+9931093	685	697	hypertension	Disease	D006973
+9931093	719	725	FK 506	Chemical	D016559
+9931093	1011	1017	FK 506	Chemical	D016559
+9931093	1134	1143	FR 139317	Chemical	C079574
+9931093	1173	1179	FK 506	Chemical	D016559
+9931093	1188	1200	hypertension	Disease	D006973
+9931093	1238	1244	FK 506	Chemical	D016559
+9931093	1335	1337	NO	Chemical	D009569
+9931093	CID	D016559	D006973
+
+20633755|t|Suxamethonium induced prolonged apnea in a patient receiving electroconvulsive therapy.
+20633755|a|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.
+20633755	0	13	Suxamethonium	Chemical	D013390
+20633755	32	37	apnea	Disease	D001049
+20633755	88	101	Suxamethonium	Chemical	D013390
+20633755	119	124	apnea	Disease	D001049
+20633755	193	222	organophosphorus (OP) poisons	Chemical	D009943
+20633755	274	283	depressed	Disease	D003866
+20633755	348	353	apnea	Disease	D001049
+20633755	423	434	OP compound	Chemical	D009943
+20633755	CID	D009943	D001049
+20633755	CID	D013390	D001049
+
+20067456|t|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.
+20067456|a|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.
+20067456	30	39	bupropion	Chemical	D016642
+20067456	48	66	sexual dysfunction	Disease	D012735
+20067456	80	118	selective serotonin reuptake inhibitor	Chemical	D017367
+20067456	238	247	bupropion	Chemical	D016642
+20067456	279	297	sexual dysfunction	Disease	D012735
+20067456	299	301	SD	Disease	D012735
+20067456	316	354	selective serotonin reuptake inhibitor	Chemical	D017367
+20067456	356	360	SSRI	Chemical	D017367
+20067456	366	368	SD	Disease	D012735
+20067456	396	401	SSRIs	Chemical	D017367
+20067456	569	573	SSRI	Chemical	D017367
+20067456	609	618	bupropion	Chemical	D016642
+20067456	904	924	Erectile Dysfunction	Disease	D007172
+20067456	1180	1189	bupropion	Chemical	D016642
+20067456	1276	1285	bupropion	Chemical	D016642
+20067456	1491	1500	bupropion	Chemical	D016642
+20067456	1597	1606	bupropion	Chemical	D016642
+20067456	1814	1816	SD	Disease	D012735
+20067456	1826	1830	SSRI	Chemical	D017367
+20067456	1858	1867	Bupropion	Chemical	D016642
+20067456	1903	1905	SD	Disease	D012735
+20067456	1917	1922	SSRIs	Chemical	D017367
+20067456	1998	2007	bupropion	Chemical	D016642
+20067456	CID	D017367	D007172
+
+18464113|t|Lamivudine for the prevention of hepatitis B virus reactivation in hepatitis-B surface antigen (HBSAG) seropositive cancer patients undergoing cytotoxic chemotherapy.
+18464113|a|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.
+18464113	0	10	Lamivudine	Chemical	D019259
+18464113	33	44	hepatitis B	Disease	D006509
+18464113	67	94	hepatitis-B surface antigen	Chemical	D006514
+18464113	96	101	HBSAG	Chemical	D006514
+18464113	116	122	cancer	Disease	D009369
+18464113	167	178	Hepatitis B	Disease	D006509
+18464113	229	242	liver disease	Disease	D008107
+18464113	254	260	Cancer	Disease	D009369
+18464113	316	336	hepatic complication	Disease	D008107
+18464113	458	464	cancer	Disease	D009369
+18464113	493	519	hematological malignancies	Disease	D019337
+18464113	533	546	HBV infection	Disease	D006509
+18464113	576	586	lamivudine	Chemical	D019259
+18464113	666	676	lamivudine	Chemical	D019259
+18464113	724	734	lamivudine	Chemical	D019259
+18464113	890	899	lamivudin	Chemical	D019259
+18464113	957	967	lamivudine	Chemical	D019259
+18464113	1078	1088	lamivudine	Chemical	D019259
+18464113	1254	1263	hepatitis	Disease	D056486
+18464113	1311	1320	hepatitis	Disease	D056486
+18464113	1342	1352	lamivudine	Chemical	D019259
+18464113	1366	1375	hepatitis	Disease	D056486
+18464113	1512	1519	alanine	Chemical	D000409
+18464113	1593	1603	lamivudine	Chemical	D019259
+18464113	1667	1677	lamivudine	Chemical	D019259
+18464113	1761	1767	cancer	Disease	D009369
+18464113	1882	1892	nucleoside	Chemical	D009705
+18464113	1896	1906	nucleotide	Chemical	D009711
+18464113	CID	D006514	D006509
+
+18308784|t|Ginsenoside Rg1 restores the impairment of learning induced by chronic morphine administration in rats.
+18308784|a|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.
+18308784	0	15	Ginsenoside Rg1	Chemical	C035054
+18308784	29	51	impairment of learning	Disease	D007859
+18308784	71	79	morphine	Chemical	D009020
+18308784	104	107	Rg1	Chemical	C035054
+18308784	114	125	ginsenoside	Chemical	D036145
+18308784	181	200	learning impairment	Disease	D007859
+18308784	242	245	Rg1	Chemical	C035054
+18308784	329	337	morphine	Chemical	D009020
+18308784	394	397	Rg1	Chemical	C035054
+18308784	401	420	learning impairment	Disease	D007859
+18308784	432	440	morphine	Chemical	D009020
+18308784	547	555	morphine	Chemical	D009020
+18308784	617	620	Rg1	Chemical	C035054
+18308784	701	709	morphine	Chemical	D009020
+18308784	841	849	Morphine	Chemical	D009020
+18308784	850	853	Rg1	Chemical	C035054
+18308784	1051	1054	Rg1	Chemical	C035054
+18308784	1109	1117	morphine	Chemical	D009020
+18308784	1220	1223	Rg1	Chemical	C035054
+18308784	1278	1286	morphine	Chemical	D009020
+18308784	1345	1353	morphine	Chemical	D009020
+18308784	1354	1357	Rg1	Chemical	C035054
+18308784	1411	1431	N-methyl-D-aspartate	Chemical	D016202
+18308784	1433	1437	NMDA	Chemical	D016202
+18308784	1459	1464	MK801	Chemical	D016291
+18308784	1483	1486	Rg1	Chemical	C035054
+18308784	1562	1570	morphine	Chemical	D009020
+18308784	1602	1610	morphine	Chemical	D009020
+18308784	1641	1645	NMDA	Chemical	D016202
+18308784	CID	D009020	D007859
+
+17931375|t|A study on the effect of the duration of subcutaneous heparin injection on bruising and pain.
+17931375|a|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.
+17931375	54	61	heparin	Chemical	D006493
+17931375	75	83	bruising	Disease	D003288
+17931375	88	92	pain	Disease	D010146
+17931375	175	183	bruising	Disease	D003288
+17931375	188	192	pain	Disease	D010146
+17931375	255	262	heparin	Chemical	D006493
+17931375	314	322	bruising	Disease	D003288
+17931375	327	331	pain	Disease	D010146
+17931375	372	379	heparin	Chemical	D006493
+17931375	474	482	bruising	Disease	D003288
+17931375	487	491	pain	Disease	D010146
+17931375	673	680	heparin	Chemical	D006493
+17931375	699	706	Heparin	Chemical	D006493
+17931375	858	866	bruising	Disease	D003288
+17931375	926	934	bruising	Disease	D003288
+17931375	942	949	heparin	Chemical	D006493
+17931375	1075	1079	pain	Disease	D010146
+17931375	1128	1132	pain	Disease	D010146
+17931375	1271	1279	bruising	Disease	D003288
+17931375	1416	1424	bruising	Disease	D003288
+17931375	1465	1469	Pain	Disease	D010146
+17931375	1484	1488	pain	Disease	D010146
+17931375	1669	1677	bruising	Disease	D003288
+17931375	1682	1686	pain	Disease	D010146
+17931375	1732	1739	heparin	Chemical	D006493
+17931375	1855	1862	heparin	Chemical	D006493
+17931375	CID	D006493	D010146
+17931375	CID	D006493	D003288
+
+15649445|t|Acute reserpine and subchronic haloperidol treatments change synaptosomal brain glutamate uptake and elicit orofacial dyskinesia in rats.
+15649445|a|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.
+15649445	6	15	reserpine	Chemical	D012110
+15649445	31	42	haloperidol	Chemical	D006220
+15649445	80	89	glutamate	Chemical	D018698
+15649445	108	128	orofacial dyskinesia	Disease	D004409
+15649445	138	147	Reserpine	Chemical	D012110
+15649445	153	164	haloperidol	Chemical	D006220
+15649445	173	193	orofacial dyskinesia	Disease	D004409
+15649445	224	242	tardive dyskinesia	Disease	D004409
+15649445	244	246	TD	Disease	D004409
+15649445	378	398	orofacial dyskinesia	Disease	D004409
+15649445	408	417	reserpine	Chemical	D012110
+15649445	433	444	haloperidol	Chemical	D006220
+15649445	469	478	Reserpine	Chemical	D012110
+15649445	670	681	Haloperidol	Chemical	D006220
+15649445	925	934	glutamate	Chemical	D018698
+15649445	993	1002	glutamate	Chemical	D018698
+15649445	1072	1081	reserpine	Chemical	D012110
+15649445	1086	1097	haloperidol	Chemical	D006220
+15649445	1151	1160	glutamate	Chemical	D018698
+15649445	1227	1247	orofacial diskinesia	Disease	D004409
+15649445	1294	1303	glutamate	Chemical	D018698
+15649445	CID	D006220	D004409
+15649445	CID	D012110	D004409
+
+14698717|t|Acute psychosis due to treatment with phenytoin in a nonepileptic patient.
+14698717|a|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.
+14698717	0	15	Acute psychosis	Disease	D011605
+14698717	38	47	phenytoin	Chemical	D010672
+14698717	94	103	psychosis	Disease	D011605
+14698717	197	206	epileptic	Disease	D004827
+14698717	302	311	psychosis	Disease	D011605
+14698717	322	331	phenytoin	Chemical	D010672
+14698717	346	366	trigeminal neuralgia	Disease	D014277
+14698717	409	427	psychotic symptoms	Disease	D011605
+14698717	449	458	phenytoin	Chemical	D010672
+14698717	477	486	epileptic	Disease	D004827
+14698717	549	557	seizures	Disease	D012640
+14698717	CID	D010672	D011605
+
+12617329|t|The effect of treatment with gum Arabic on gentamicin nephrotoxicity in rats: a preliminary study.
+12617329|a|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.
+12617329	29	39	gum Arabic	Chemical	D006170
+12617329	43	53	gentamicin	Chemical	D005839
+12617329	54	68	nephrotoxicity	Disease	D007674
+12617329	168	178	gum Arabic	Chemical	D006170
+12617329	182	201	acute renal failure	Disease	D058186
+12617329	213	223	gentamicin	Chemical	D005839
+12617329	225	227	GM	Chemical	D005839
+12617329	229	243	nephrotoxicity	Disease	D007674
+12617329	340	350	gum Arabic	Chemical	D006170
+12617329	395	405	gum Arabic	Chemical	D006170
+12617329	438	448	gum Arabic	Chemical	D006170
+12617329	468	470	GM	Chemical	D005839
+12617329	552	566	Nephrotoxicity	Disease	D007674
+12617329	615	625	creatinine	Chemical	D003404
+12617329	630	634	urea	Chemical	D014508
+12617329	661	672	glutathione	Chemical	D005978
+12617329	674	677	GSH	Chemical	D005978
+12617329	812	822	gum Arabic	Chemical	D006170
+12617329	827	829	GM	Chemical	D005839
+12617329	854	864	creatinine	Chemical	D003404
+12617329	869	873	urea	Chemical	D014508
+12617329	986	988	GM	Chemical	D005839
+12617329	1022	1025	GSH	Chemical	D005978
+12617329	1072	1074	GM	Chemical	D005839
+12617329	1086	1088	GM	Chemical	D005839
+12617329	1106	1122	tubular necrosis	Disease	D007683
+12617329	1173	1175	GM	Chemical	D005839
+12617329	1190	1200	gum Arabic	Chemical	D006170
+12617329	1221	1223	GM	Chemical	D005839
+12617329	1265	1275	gum Arabic	Chemical	D006170
+12617329	1375	1377	GM	Chemical	D005839
+12617329	1378	1392	nephrotoxicity	Disease	D007674
+12617329	1493	1514	chronic renal failure	Disease	D007676
+12617329	CID	D005839	D058186
+12617329	CID	D006170	D058186
+
+12523465|t|Visual hallucinations associated with zonisamide.
+12523465|a|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.
+12523465	0	21	Visual hallucinations	Disease	D006212
+12523465	38	48	zonisamide	Chemical	C022189
+12523465	50	60	Zonisamide	Chemical	C022189
+12523465	131	139	seizures	Disease	D012640
+12523465	150	171	visual hallucinations	Disease	D006212
+12523465	282	303	visual hallucinations	Disease	D006212
+12523465	336	346	zonisamide	Chemical	C022189
+12523465	434	442	epilepsy	Disease	D004827
+12523465	524	545	visual hallucinations	Disease	D006212
+12523465	681	702	visual hallucinations	Disease	D006212
+12523465	808	818	zonisamide	Chemical	C022189
+12523465	1082	1092	zonisamide	Chemical	C022189
+12523465	CID	C022189	D006212
+
+11961407|t|GLEPP1 receptor tyrosine phosphatase (Ptpro) in rat PAN nephrosis. A marker of acute podocyte injury.
+11961407|a|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.
+11961407	16	24	tyrosine	Chemical	D014443
+11961407	52	55	PAN	Chemical	D011692
+11961407	56	65	nephrosis	Disease	D009401
+11961407	183	191	tyrosine	Chemical	D014443
+11961407	451	468	glomerular injury	Disease	D007674
+11961407	646	671	Puromycin aminonucleoside	Chemical	D011692
+11961407	672	681	nephrosis	Disease	D009401
+11961407	733	758	puromycin aminonucleoside	Chemical	D011692
+11961407	760	763	PAN	Chemical	D011692
+11961407	849	852	PAN	Chemical	D011692
+11961407	904	915	proteinuria	Disease	D011507
+11961407	993	1004	proteinuria	Disease	D011507
+11961407	1021	1039	glomerulosclerosis	Disease	D005921
+11961407	1790	1793	PAN	Chemical	D011692
+11961407	CID	D011692	D011507
+11961407	CID	D011692	D009401
+
+9401499|t|Ticlopidine-induced aplastic anemia: report of three Chinese patients and review of the literature.
+9401499|a|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.
+9401499	0	11	Ticlopidine	Chemical	D013988
+9401499	20	35	aplastic anemia	Disease	D000741
+9401499	143	154	ticlopidine	Chemical	D013988
+9401499	163	178	aplastic anemia	Disease	D000741
+9401499	558	573	Agranulocytosis	Disease	D000380
+9401499	614	625	ticlopidine	Chemical	D013988
+9401499	799	822	bone marrow suppression	Disease	D001855
+9401499	838	849	ticlopidine	Chemical	D013988
+9401499	858	873	aplastic anemia	Disease	D000741
+9401499	994	1001	calcium	Chemical	D002118
+9401499	CID	D013988	D000741
+9401499	CID	D013988	D000380
+
+2273650|t|Facilitation of memory retrieval by pre-test morphine and its state dependency in the step-through type passive avoidance learning test in mice.
+2273650|a|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.
+2273650	45	53	morphine	Chemical	D009020
+2273650	145	152	Amnesia	Disease	D000647
+2273650	165	176	scopolamine	Chemical	D012601
+2273650	181	194	cycloheximide	Chemical	D003513
+2273650	212	220	morphine	Chemical	D009020
+2273650	281	289	morphine	Chemical	D009020
+2273650	356	364	naloxone	Chemical	D009270
+2273650	412	423	scopolamine	Chemical	D012601
+2273650	447	458	scopolamine	Chemical	D012601
+2273650	467	474	amnesia	Disease	D000647
+2273650	512	525	cycloheximide	Chemical	D003513
+2273650	548	561	cycloheximide	Chemical	D003513
+2273650	570	577	amnesia	Disease	D000647
+2273650	655	663	morphine	Chemical	D009020
+2273650	694	702	morphine	Chemical	D009020
+2273650	CID	D012601	D000647
+2273650	CID	D003513	D000647
+
+10683478|t|Test conditions influence the response to a drug challenge in rodents.
+10683478|a|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.
+10683478	296	307	Apomorphine	Chemical	D001058
+10683478	324	340	dopamine agonist	Chemical	D018491
+10683478	417	428	hypothermia	Disease	D007035
+10683478	465	473	dopamine	Chemical	D004298
+10683478	583	594	apomorphine	Chemical	D001058
+10683478	699	710	apomorphine	Chemical	D001058
+10683478	719	732	hyperactivity	Disease	D006948
+10683478	879	890	apomorphine	Chemical	D001058
+10683478	912	923	hypothermia	Disease	D007035
+10683478	934	945	apomorphine	Chemical	D001058
+10683478	1236	1247	apomorphine	Chemical	D001058
+10683478	1316	1324	Dopamine	Chemical	D004298
+10683478	1342	1347	DOPAC	Chemical	D015102
+10683478	1348	1350	DA	Chemical	D018491
+10683478	1355	1358	HVA	Chemical	D006719
+10683478	1359	1361	DA	Chemical	D018491
+10683478	1490	1501	apomorphine	Chemical	D001058
+10683478	1533	1541	dopamine	Chemical	D004298
+10683478	CID	D001058	D007035
+10683478	CID	D001058	D006948
+