6794356|t|Tricuspid valve regurgitation and lithium carbonate toxicity in a newborn infant.
6794356|a|A newborn with massive tricuspid regurgitation, atrial flutter, congestive heart failure, and a high serum lithium level is described. This is the first patient to initially manifest tricuspid regurgitation and atrial flutter, and the 11th described patient with cardiac disease among infants exposed to lithium compounds in the first trimester of pregnancy. Sixty-three percent of these infants had tricuspid valve involvement. Lithium carbonate may be a factor in the increasing incidence of congenital heart disease when taken during early pregnancy. It also causes neurologic depression, cyanosis, and cardiac arrhythmia when consumed prior to delivery.
6794356	0	29	Tricuspid valve regurgitation	Disease	D014262
6794356	34	51	lithium carbonate	Chemical	D016651
6794356	52	60	toxicity	Disease	D064420
6794356	105	128	tricuspid regurgitation	Disease	D014262
6794356	130	144	atrial flutter	Disease	D001282
6794356	146	170	congestive heart failure	Disease	D006333
6794356	189	196	lithium	Chemical	D008094
6794356	265	288	tricuspid regurgitation	Disease	D014262
6794356	293	307	atrial flutter	Disease	D001282
6794356	345	360	cardiac disease	Disease	D006331
6794356	386	393	lithium	Chemical	D008094
6794356	511	528	Lithium carbonate	Chemical	D016651
6794356	576	600	congenital heart disease	Disease	D006331
6794356	651	672	neurologic depression	Disease	D003866
6794356	674	682	cyanosis	Disease	D003490
6794356	688	706	cardiac arrhythmia	Disease	D001145
6794356	CID	D016651	D003490
6794356	CID	D016651	D001145
6794356	CID	D016651	D003866

6504332|t|Phenobarbital-induced dyskinesia in a neurologically-impaired child.
6504332|a|A 2-year-old child with known neurologic impairment developed a dyskinesia soon after starting phenobarbital therapy for seizures. Known causes of movement disorders were eliminated after evaluation. On repeat challenge with phenobarbital, the dyskinesia recurred. Phenobarbital should be added to the list of anticonvulsant drugs that can cause movement disorders.
6504332	0	13	Phenobarbital	Chemical	D010634
6504332	22	32	dyskinesia	Disease	D004409
6504332	38	61	neurologically-impaired	Disease	D009422
6504332	99	120	neurologic impairment	Disease	D009422
6504332	133	143	dyskinesia	Disease	D004409
6504332	164	177	phenobarbital	Chemical	D010634
6504332	190	198	seizures	Disease	D012640
6504332	216	234	movement disorders	Disease	D009069
6504332	294	307	phenobarbital	Chemical	D010634
6504332	313	323	dyskinesia	Disease	D004409
6504332	334	347	Phenobarbital	Chemical	D010634
6504332	415	433	movement disorders	Disease	D009069
6504332	CID	D010634	D004409

6436733|t|Acute changes of blood ammonia may predict short-term adverse effects of valproic acid.
6436733|a|Valproic acid (VPA) was given to 24 epileptic patients who were already being treated with other antiepileptic drugs. A standardized loading dose of VPA was administered, and venous blood was sampled at 0, 1, 2, 3, and 4 hours. Ammonia (NH3) was higher in patients who, during continuous therapy, complained of drowsiness (7 patients) than in those who were symptom-free (17 patients), although VPA plasma levels were similar in both groups. By measuring VPA-induced changes of blood NH3 content, it may be possible to identify patients at higher risk of obtundation when VPA is given chronically.
6436733	23	30	ammonia	Chemical	D000641
6436733	73	86	valproic acid	Chemical	D014635
6436733	88	101	Valproic acid	Chemical	D014635
6436733	103	106	VPA	Chemical	D014635
6436733	124	133	epileptic	Disease	D004827
6436733	237	240	VPA	Chemical	D014635
6436733	316	323	Ammonia	Chemical	D000641
6436733	325	328	NH3	Chemical	D000641
6436733	399	409	drowsiness	Disease	D006970
6436733	483	486	VPA	Chemical	D014635
6436733	543	546	VPA	Chemical	D014635
6436733	572	575	NH3	Chemical	D000641
6436733	660	663	VPA	Chemical	D014635
6436733	CID	D014635	D006970
6436733	CID	D000641	D006970

6293644|t|Effects of calcitonin on rat extrapyramidal motor system: behavioral and biochemical data.
6293644|a|The effects of i.v.c. injection of human and salmon calcitonin on biochemical and behavioral parameters related to the extrapyramidal motor system, were investigated in male rats. Calcitonin injection resulted in a potentiation of haloperidol-induced catalepsy and a partial prevention of apomorphine-induced hyperactivity. Moreover calcitonin induced a significant decrease in nigral GAD activity but no change in striatal DA and DOPAC concentration or GAD activity. The results are discussed in view of a primary action of calcitonin on the striatonigral GABAergic pathway mediating the DA-related behavioral messages of striatal origin.
6293644	322	333	haloperidol	Chemical	D006220
6293644	342	351	catalepsy	Disease	D002375
6293644	380	391	apomorphine	Chemical	D001058
6293644	400	413	hyperactivity	Disease	D006948
6293644	515	517	DA	Chemical	D004298
6293644	522	527	DOPAC	Chemical	D015102
6293644	680	682	DA	Chemical	D004298
6293644	CID	D006220	D002375
6293644	CID	D001058	D006948

6203632|t|Development of isoproterenol-induced cardiac hypertrophy.
6203632|a|The development of cardiac hypertrophy was studied in adult female Wistar rats following daily subcutaneous injections of isoproterenol (ISO) (0.3 mg/kg body weight). A time course was established for the change in tissue mass, RNA and DNA content, as well as hydroxyproline content. Heart weight increased 44% after 8 days of treatment with a half time of 3.4 days. Ventricular RNA content was elevated 26% after 24 h of a single injection and reached a maximal level following 8 days of therapy. The half time for RNA accumulation was 2.0 days. The total content of hydroxyproline remained stable during the first 2 days of treatment but increased 46% after 4 days of therapy. Ventricular DNA content was unchanged during the early stage (1-4 days) of hypertrophic growth but increased to a new steady-state level 19% above the controls after 8 days of treatment. Intraventricular pressures and coronary flow measures were similar for control and experimental animals following 4 days of developed hypertrophy. However, dP/dt in the ISO-treated hearts was slightly but significantly (P less than 0.05) elevated. These data indicate that the adaptive response to ISO shows an early hypertrophic phase (1-4 days) characterized by a substantial increase in RNA content and cardiac mass in the absence of changes in DNA. However, prolonged stimulation (8-12 days) appears to represent a complex integration of both cellular hypertrophy and hyperplasia within the heart.
6203632	15	28	isoproterenol	Chemical	D007545
6203632	37	56	cardiac hypertrophy	Disease	D006332
6203632	77	96	cardiac hypertrophy	Disease	D006332
6203632	180	193	isoproterenol	Chemical	D007545
6203632	195	198	ISO	Chemical	D007545
6203632	318	332	hydroxyproline	Chemical	D006909
6203632	626	640	hydroxyproline	Chemical	D006909
6203632	812	824	hypertrophic	Disease	D006984
6203632	1058	1069	hypertrophy	Disease	D006984
6203632	1093	1096	ISO	Chemical	D007545
6203632	1222	1225	ISO	Chemical	D007545
6203632	1241	1253	hypertrophic	Disease	D006984
6203632	1480	1491	hypertrophy	Disease	D006984
6203632	1496	1507	hyperplasia	Disease	D006965
6203632	CID	D007545	D006332
6203632	CID	D007545	D006965

3131282|t|Co-carcinogenic effect of retinyl acetate on forestomach carcinogenesis of male F344 rats induced with butylated hydroxyanisole.
3131282|a|The potential modifying effect of retinyl acetate (RA) on butylated hydroxyanisole (BHA)-induced rat forestomach tumorigenesis was examined. Male F344 rats, 5 weeks of age, were maintained on diet containing 1% or 2% BHA by weight and simultaneously on drinking water supplemented with RA at various concentrations (w/v) for 52 weeks. In groups given 2% BHA, although marked hyperplastic changes of the forestomach epithelium were observed in all animals, co-administration of 0.25% RA significantly (P less than 0.05) increased the incidence of forestomach tumors (squamous cell papilloma and carcinoma) to 60% (9/15, 2 rats with carcinoma) from 15% (3/20, one rat with carcinoma) in the group given RA-free water. In rats given 1% BHA, RA co-administered at a dose of 0.05, 0.1, 0.2 or 0.25% showed a dose-dependent enhancing effect on the development of the BHA-induced epithelial hyperplasia. Tumors, all papillomas, were induced in 3 rats (17%) with 0.25% RA and in one rat (10%) with 0.05% RA co-administration. RA alone did not induce hyperplastic changes in the forestomach. These findings indicate that RA acted as a co-carcinogen in the BHA forestomach carcinogenesis of the rat.
3131282	3	15	carcinogenic	Disease	D063646
3131282	26	41	retinyl acetate	Chemical	C009166
3131282	45	71	forestomach carcinogenesis	Disease	D013274
3131282	103	127	butylated hydroxyanisole	Chemical	D002083
3131282	163	178	retinyl acetate	Chemical	C009166
3131282	180	182	RA	Chemical	C009166
3131282	187	211	butylated hydroxyanisole	Chemical	D002083
3131282	213	216	BHA	Chemical	D002083
3131282	230	255	forestomach tumorigenesis	Disease	D013274
3131282	346	349	BHA	Chemical	D002083
3131282	415	417	RA	Chemical	C009166
3131282	483	486	BHA	Chemical	D002083
3131282	612	614	RA	Chemical	C009166
3131282	675	693	forestomach tumors	Disease	D013274
3131282	695	718	squamous cell papilloma	Disease	D010212
3131282	723	732	carcinoma	Disease	D002277
3131282	760	769	carcinoma	Disease	D002277
3131282	800	809	carcinoma	Disease	D002277
3131282	830	832	RA	Chemical	C009166
3131282	862	865	BHA	Chemical	D002083
3131282	867	869	RA	Chemical	C009166
3131282	990	993	BHA	Chemical	D002083
3131282	1002	1024	epithelial hyperplasia	Disease	D017573
3131282	1026	1032	Tumors	Disease	D009369
3131282	1038	1048	papillomas	Disease	D010212
3131282	1090	1092	RA	Chemical	C009166
3131282	1125	1127	RA	Chemical	C009166
3131282	1147	1149	RA	Chemical	C009166
3131282	1241	1243	RA	Chemical	C009166
3131282	1276	1279	BHA	Chemical	D002083
3131282	1280	1306	forestomach carcinogenesis	Disease	D013274
3131282	CID	D002083	D013274

3115150|t|Ketanserin pretreatment reverses alfentanil-induced muscle rigidity.
3115150|a|Systemic pretreatment with ketanserin, a relatively specific type-2 serotonin receptor antagonist, significantly attenuated the muscle rigidity produced in rats by the potent short-acting opiate agonist alfentanil. Following placement of subcutaneous electrodes in each animal's left gastrocnemius muscle, rigidity was assessed by analyzing root-mean-square electromyographic activity. Intraperitoneal ketanserin administration at doses of 0.63 and 2.5 mg/kg prevented the alfentanil-induced increase in electromyographic activity compared with animals pretreated with saline. Chlordiazepoxide at doses up to 10 mg/kg failed to significantly influence the rigidity produced by alfentanil. Despite the absence of rigidity, animals that received ketanserin (greater than 0.31 mg/kg i.p.) followed by alfentanil were motionless, flaccid, and less responsive to external stimuli than were animals receiving alfentanil alone. Rats that received ketanserin and alfentanil exhibited less rearing and exploratory behavior at the end of the 60-min recording period than did animals that received ketanserin alone. These results, in combination with previous work, suggest that muscle rigidity, a clinically relevant side-effect of parenteral narcotic administration, may be partly mediated via serotonergic pathways. Pretreatment with type-2 serotonin antagonists may be clinically useful in attenuating opiate-induced rigidity, although further studies will be necessary to assess the interaction of possibly enhanced CNS, cardiovascular, and respiratory depression.
3115150	0	10	Ketanserin	Chemical	D007650
3115150	33	43	alfentanil	Chemical	D015760
3115150	52	67	muscle rigidity	Disease	D009127
3115150	96	106	ketanserin	Chemical	D007650
3115150	137	146	serotonin	Chemical	D012701
3115150	197	212	muscle rigidity	Disease	D009127
3115150	272	282	alfentanil	Chemical	D015760
3115150	375	383	rigidity	Disease	D009127
3115150	471	481	ketanserin	Chemical	D007650
3115150	542	552	alfentanil	Chemical	D015760
3115150	646	662	Chlordiazepoxide	Chemical	D002707
3115150	725	733	rigidity	Disease	D009127
3115150	746	756	alfentanil	Chemical	D015760
3115150	781	789	rigidity	Disease	D009127
3115150	813	823	ketanserin	Chemical	D007650
3115150	867	877	alfentanil	Chemical	D015760
3115150	972	982	alfentanil	Chemical	D015760
3115150	1009	1019	ketanserin	Chemical	D007650
3115150	1024	1034	alfentanil	Chemical	D015760
3115150	1156	1166	ketanserin	Chemical	D007650
3115150	1237	1252	muscle rigidity	Disease	D009127
3115150	1402	1411	serotonin	Chemical	D012701
3115150	1479	1487	rigidity	Disease	D009127
3115150	1584	1626	cardiovascular, and respiratory depression	Disease	D002318|D012131	cardiovascular depression|respiratory depression
3115150	CID	D015760	D009127

2917114|t|Glycopyrronium requirements for antagonism of the muscarinic side effects of edrophonium.
2917114|a|We have compared, in 60 adult patients, the cardiovascular effects of glycopyrronium 5 micrograms kg-1 and 10 micrograms kg-1 given either simultaneously or 1 min before edrophonium 1 mg kg-1. Significant differences between the four groups were detected (P less than 0.001). Both groups receiving 10 micrograms kg-1 showed increases in heart rate of up to 30 beat min-1 (95% confidence limits 28-32 beat min-1). Use of glycopyrronium 5 micrograms kg-1 provided greater cardiovascular stability and, given 1 min before the edrophonium, was sufficient to minimize early, edrophonium-induced bradycardias. This low dose of glycopyrronium provided good control of oropharyngeal secretions.
2917114	0	14	Glycopyrronium	Chemical	D006024
2917114	77	88	edrophonium	Chemical	D004491
2917114	160	174	glycopyrronium	Chemical	D006024
2917114	260	271	edrophonium	Chemical	D004491
2917114	510	524	glycopyrronium	Chemical	D006024
2917114	613	624	edrophonium	Chemical	D004491
2917114	660	671	edrophonium	Chemical	D004491
2917114	680	692	bradycardias	Disease	D001919
2917114	711	725	glycopyrronium	Chemical	D006024
2917114	CID	D004491	D001919

2564649|t|Involvement of locus coeruleus and noradrenergic neurotransmission in fentanyl-induced muscular rigidity in the rat.
2564649|a|Whereas muscular rigidity is a well-known side effect that is associated with high-dose fentanyl anesthesia, a paucity of information exists with regard to its underlying mechanism(s). We investigated in this study the possible engagement of locus coeruleus of the pons in this phenomenon, using male Sprague-Dawley rats anesthetized with ketamine. Under proper control of respiration, body temperature and end-tidal CO2, intravenous administration of fentanyl (50 or 100 micrograms/kg) consistently promoted an increase in electromyographic activity recorded from the gastrocnemius and abdominal rectus muscles. Such an induced muscular rigidity by the narcotic agent was significantly antagonized or even reduced by prior electrolytic lesions of the locus coeruleus or pretreatment with the alpha-adrenoceptor blocker, prazosin. Microinjection of fentanyl (2.5 micrograms/50 nl) directly into this pontine nucleus, on the other hand, elicited discernible electromyographic excitation. It is speculated that the induction of muscular rigidity by fentanyl may involve the coerulospinal noradrenergic fibers to the spinal motoneurons.
2564649	70	78	fentanyl	Chemical	D005283
2564649	87	104	muscular rigidity	Disease	D009127
2564649	125	142	muscular rigidity	Disease	D009127
2564649	205	213	fentanyl	Chemical	D005283
2564649	456	464	ketamine	Chemical	D007649
2564649	534	537	CO2	Chemical	D002245
2564649	569	577	fentanyl	Chemical	D005283
2564649	746	763	muscular rigidity	Disease	D009127
2564649	938	946	prazosin	Chemical	D011224
2564649	966	974	fentanyl	Chemical	D005283
2564649	1143	1160	muscular rigidity	Disease	D009127
2564649	1164	1172	fentanyl	Chemical	D005283
2564649	CID	D005283	D009127

2339463|t|Cerebral sinus thrombosis as a potential hazard of antifibrinolytic treatment in menorrhagia.
2339463|a|We describe a 42-year-old woman who developed superior sagittal and left transverse sinus thrombosis associated with prolonged epsilon-aminocaproic acid therapy for menorrhagia. This antifibrinolytic agent has been used in women with menorrhagia to promote clotting and reduce blood loss. Although increased risk of thromboembolic disease has been reported during treatment with epsilon-aminocaproic acid, cerebral sinus thrombosis has not been previously described. Careful use of epsilon-aminocaproic acid therapy is recommended.
2339463	0	25	Cerebral sinus thrombosis	Disease	D012851
2339463	81	92	menorrhagia	Disease	D008595
2339463	149	194	sagittal and left transverse sinus thrombosis	Disease	D020225|D020227	sagittal sinus thrombosis|left transverse sinus thrombosis
2339463	221	246	epsilon-aminocaproic acid	Chemical	D015119
2339463	259	270	menorrhagia	Disease	D008595
2339463	328	339	menorrhagia	Disease	D008595
2339463	371	381	blood loss	Disease	D006473
2339463	410	432	thromboembolic disease	Disease	D013923
2339463	473	498	epsilon-aminocaproic acid	Chemical	D015119
2339463	500	525	cerebral sinus thrombosis	Disease	D012851
2339463	576	601	epsilon-aminocaproic acid	Chemical	D015119
2339463	CID	D015119	D020225

1545575|t|Hemorrhagic cystitis complicating bone marrow transplantation.
1545575|a|Hemorrhagic cystitis is a potentially serious complication of high-dose cyclophosphamide therapy administered before bone marrow transplantation. As standard practice at our institution, patients who are scheduled to receive a bone marrow transplant are treated prophylactically with forced hydration and bladder irrigation. In an attempt to obviate the inconvenience of bladder irrigation, we conducted a feasibility trial of uroprophylaxis with mesna, which neutralizes the hepatic metabolite of cyclophosphamide that causes hemorrhagic cystitis. Of 97 patients who received standard prophylaxis, 4 had symptomatic hemorrhagic cystitis. In contrast, two of four consecutive patients who received mesna uroprophylaxis before allogeneic bone marrow transplantation had severe hemorrhagic cystitis for at least 2 weeks. Because of this suboptimal result, we resumed the use of bladder irrigation and forced hydration to minimize the risk of hemorrhagic cystitis.
1545575	0	20	Hemorrhagic cystitis	Disease	D006470|D003556	Hemorrhagic|cystitis
1545575	63	83	Hemorrhagic cystitis	Disease	D006470|D003556	Hemorrhagic|cystitis
1545575	135	151	cyclophosphamide	Chemical	D003520
1545575	510	515	mesna	Chemical	D015080
1545575	561	577	cyclophosphamide	Chemical	D003520
1545575	590	610	hemorrhagic cystitis	Disease	D006470|D003556	hemorrhagic|cystitis
1545575	680	700	hemorrhagic cystitis	Disease	D006470|D003556	hemorrhagic|cystitis
1545575	761	766	mesna	Chemical	D015080
1545575	839	859	hemorrhagic cystitis	Disease	D006470|D003556	hemorrhagic|cystitis
1545575	1003	1023	hemorrhagic cystitis	Disease	D006470|D003556	hemorrhagic|cystitis
1545575	CID	D003520	D006470
1545575	CID	D003520	D003556

1286498|t|Reversal of central benzodiazepine effects by flumazenil after intravenous conscious sedation with diazepam and opioids: report of a double-blind multicenter study. The Flumazenil in Intravenous Conscious Sedation with Diazepam Multicenter Study Group II.
1286498|a|The efficacy and safety of a new benzodiazepine antagonist, flumazenil, were assessed in a double-blind multicenter study. Flumazenil (mean dose, 0.76 mg) or placebo (mean dose, 8.9 ml) was administered intravenously to 130 and 67 patients, respectively, who had been given diazepam in conjunction with an opioid (fentanyl, meperidine, or morphine) for the induction and maintenance of intravenous conscious sedation for diagnostic or therapeutic surgical procedures. The group assessable for efficacy comprised 122 patients treated with flumazenil and 64 patients given placebo. After 5 minutes, 80/115 (70%) flumazenil-treated patients, compared with 21/63 (33%) placebo-treated patients, were completely awake and alert, as indicated by a score of 5 on the Observer's Assessment of Alertness/Sedation Scale. Ninety-five percent of patients in each group who attained a score of 5 at the 5-minute assessment showed no loss of alertness throughout the 180-minute assessment period. Flumazenil-treated patients also performed significantly better on the Finger-to-Nose Test and the recall of pictures shown at the 5-minute assessment. Flumazenil was well tolerated, with no serious adverse effects reported. Thirty-nine (30%) of flumazenil-treated patients, compared with 17 (25%) of placebo-treated patients had one or more drug-related adverse experiences. The most common adverse effects were nausea and vomiting in the flumazenil group and nausea and injection-site pain in the placebo group. Flumazenil was found to promptly reverse sedation induced by diazepam in the presence of opioids.
1286498	20	34	benzodiazepine	Chemical	D001569
1286498	46	56	flumazenil	Chemical	D005442
1286498	99	107	diazepam	Chemical	D003975
1286498	169	179	Flumazenil	Chemical	D005442
1286498	219	227	Diazepam	Chemical	D003975
1286498	289	303	benzodiazepine	Chemical	D001569
1286498	316	326	flumazenil	Chemical	D005442
1286498	379	389	Flumazenil	Chemical	D005442
1286498	530	538	diazepam	Chemical	D003975
1286498	570	578	fentanyl	Chemical	D005283
1286498	580	590	meperidine	Chemical	D008614
1286498	595	603	morphine	Chemical	D009020
1286498	794	804	flumazenil	Chemical	D005442
1286498	866	876	flumazenil	Chemical	D005442
1286498	1239	1249	Flumazenil	Chemical	D005442
1286498	1391	1401	Flumazenil	Chemical	D005442
1286498	1485	1495	flumazenil	Chemical	D005442
1286498	1652	1658	nausea	Disease	D009325
1286498	1663	1671	vomiting	Disease	D014839
1286498	1679	1689	flumazenil	Chemical	D005442
1286498	1700	1706	nausea	Disease	D009325
1286498	1726	1730	pain	Disease	D010146
1286498	1753	1763	Flumazenil	Chemical	D005442
1286498	1814	1822	diazepam	Chemical	D003975
1286498	CID	D005442	D009325
1286498	CID	D005442	D014839

839274|t|Hepatic adenomas and focal nodular hyperplasia of the liver in young women on oral contraceptives: case reports.
839274|a|Two cases of hepatic adenoma and one of focal nodular hyperplasia presumably associated with the use of oral contraceptives, are reported. Special reference is made to their clinical presentation, which may be totally asymptomatic. Liver-function tests are of little diagnostic value, but valuable information may be obtained from both liver scanning and hepatic angiography. Histologic differences and clinical similarities between hepatic adenoma and focal nodular hyperplasia of the liver are discussed.
839274	8	16	adenomas	Disease	D000236
839274	21	46	focal nodular hyperplasia	Disease	D020518
839274	78	97	oral contraceptives	Chemical	D003276
839274	134	141	adenoma	Disease	D000236
839274	153	178	focal nodular hyperplasia	Disease	D020518
839274	217	236	oral contraceptives	Chemical	D003276
839274	554	561	adenoma	Disease	D000236
839274	566	591	focal nodular hyperplasia	Disease	D020518
839274	CID	D003276	D020518
839274	CID	D003276	D000236

591536|t|Arterial thromboembolism in patients receiving systemic heparin therapy: a complication associated with heparin-induced thrombocytopenia.
591536|a|Arterial thromboembolism is a recognized complication of systemic heparin therapy. Characteristic of the entity is arterial occlusion by platelet-fibrin thrombi with distal ischemia occurring four to twenty days after the initiation of heparin therapy, preceded by profound thrombocytopenia with platelet counts in the range of 30,000 to 40,000 per cubic millimeter. The clinically apparent occlusion may be preceded by gastrointestinal and musculoskeletal symptoms that appear to be ischemic in origin, and might serve to warn the clinician of these complications. Previous reports of these phenomena as well as recent studies of the effect of heparin are reviewed. The common factor relating thromboembolism and thrombocytopenia is heparin-induced platelet aggregation. Appropriate treatment consists of discontinuation of heparin, and anticoagulation with sodium warfarin if necessary. Vascular procedures are performed as indicated.
591536	9	24	thromboembolism	Disease	D013923
591536	56	63	heparin	Chemical	D006493
591536	104	111	heparin	Chemical	D006493
591536	120	136	thrombocytopenia	Disease	D013921
591536	147	162	thromboembolism	Disease	D013923
591536	204	211	heparin	Chemical	D006493
591536	253	271	arterial occlusion	Disease	D001157
591536	291	298	thrombi	Disease	D013927
591536	311	319	ischemia	Disease	D007511
591536	374	381	heparin	Chemical	D006493
591536	412	428	thrombocytopenia	Disease	D013921
591536	558	603	gastrointestinal and musculoskeletal symptoms	Disease	D005767|D009140	gastrointestinal symptoms|musculoskeletal symptoms
591536	622	630	ischemic	Disease	D007511
591536	783	790	heparin	Chemical	D006493
591536	832	847	thromboembolism	Disease	D013923
591536	852	868	thrombocytopenia	Disease	D013921
591536	872	879	heparin	Chemical	D006493
591536	888	908	platelet aggregation	Disease	D001791
591536	963	970	heparin	Chemical	D006493
591536	997	1012	sodium warfarin	Chemical	D014859
591536	CID	D006493	D001157
591536	CID	D006493	D013921

20735774|t|Long-term prognosis for transplant-free survivors of paracetamol-induced acute liver failure.
20735774|a|BACKGROUND: The prognosis for transplant-free survivors of paracetamol-induced acute liver failure remains unknown. AIM: To examine whether paracetamol-induced acute liver failure increases long-term mortality. METHODS: We followed up all transplant-free survivors of paracetamol-induced acute liver injury, hospitalized in a Danish national referral centre during 1984-2004. We compared age-specific mortality rates from 1 year post-discharge through 2008 between those in whom the liver injury led to an acute liver failure and those in whom it did not. RESULTS: We included 641 patients. On average, age-specific mortality rates were slightly higher for the 101 patients whose paracetamol-induced liver injury had caused an acute liver failure (adjusted mortality rate ratio = 1.70, 95% CI 1.02-2.85), but the association was age-dependent, and no survivors of acute liver failure died of liver disease, whereas suicides were frequent in both groups. These observations speak against long-term effects of acute liver failure. More likely, the elevated mortality rate ratio resulted from incomplete adjustment for the greater prevalence of substance abuse among survivors of acute liver failure. CONCLUSIONS: Paracetamol-induced acute liver failure did not affect long-term mortality. Clinical follow-up may be justified by the cause of the liver failure, but not by the liver failure itself.
20735774	53	64	paracetamol	Chemical	D000082
20735774	73	92	acute liver failure	Disease	D017114
20735774	153	164	paracetamol	Chemical	D000082
20735774	173	192	acute liver failure	Disease	D017114
20735774	234	245	paracetamol	Chemical	D000082
20735774	254	273	acute liver failure	Disease	D017114
20735774	362	373	paracetamol	Chemical	D000082
20735774	382	400	acute liver injury	Disease	D056486
20735774	577	589	liver injury	Disease	D056486
20735774	600	619	acute liver failure	Disease	D017114
20735774	774	785	paracetamol	Chemical	D000082
20735774	794	806	liver injury	Disease	D056486
20735774	821	840	acute liver failure	Disease	D017114
20735774	958	977	acute liver failure	Disease	D017114
20735774	986	999	liver disease	Disease	D008107
20735774	1102	1121	acute liver failure	Disease	D017114
20735774	1236	1251	substance abuse	Disease	D019966
20735774	1271	1290	acute liver failure	Disease	D017114
20735774	1305	1316	Paracetamol	Chemical	D000082
20735774	1325	1344	acute liver failure	Disease	D017114
20735774	1437	1450	liver failure	Disease	D017093
20735774	1467	1480	liver failure	Disease	D017093
20735774	CID	D000082	D017114

20705401|t|Serotonin 6 receptor gene is associated with methamphetamine-induced psychosis in a Japanese population.
20705401|a|BACKGROUND: Altered serotonergic neural transmission is hypothesized to be a susceptibility factor for psychotic disorders such as schizophrenia. The serotonin 6 (5-HT6) receptor is therapeutically targeted by several second generation antipsychotics, such as clozapine and olanzapine, and d-amphetamine-induced hyperactivity in rats is corrected with the use of a selective 5-HT6 receptor antagonist. In addition, the disrupted prepulse inhibition induced by d-amphetamine or phencyclidine was restored by 5-HT6 receptor antagonist in an animal study using rats. These animal models were considered to reflect the positive symptoms of schizophrenia, and the above evidence suggests that altered 5-HT6 receptors are involved in the pathophysiology of psychotic disorders. The symptoms of methamphetamine (METH)-induced psychosis are similar to those of paranoid type schizophrenia. Therefore, we conducted an analysis of the association of the 5-HT6 gene (HTR6) with METH-induced psychosis. METHOD: Using five tagging SNPs (rs6693503, rs1805054, rs4912138, rs3790757 and rs9659997), we conducted a genetic association analysis of case-control samples (197 METH-induced psychosis patients and 337 controls) in the Japanese population. The age and sex of the control subjects did not differ from those of the methamphetamine dependence patients. RESULTS: rs6693503 was associated with METH-induced psychosis patients in the allele/genotype-wise analysis. Moreover, this association remained significant after Bonferroni correction. In the haplotype-wise analysis, we detected an association between two markers (rs6693503 and rs1805054) and three markers (rs6693503, rs1805054 and rs4912138) in HTR6 and METH-induced psychosis patients, respectively. CONCLUSION: HTR6 may play an important role in the pathophysiology of METH-induced psychosis in the Japanese population.
20705401	0	9	Serotonin	Chemical	D012701
20705401	45	60	methamphetamine	Chemical	D008694
20705401	69	78	psychosis	Disease	D011605
20705401	208	227	psychotic disorders	Disease	D011605
20705401	236	249	schizophrenia	Disease	D012559
20705401	255	264	serotonin	Chemical	D012701
20705401	268	272	5-HT	Chemical	D012701
20705401	365	374	clozapine	Chemical	D003024
20705401	379	389	olanzapine	Chemical	C076029
20705401	395	408	d-amphetamine	Chemical	D003913
20705401	417	430	hyperactivity	Disease	D006948
20705401	480	484	5-HT	Chemical	D012701
20705401	565	578	d-amphetamine	Chemical	D003913
20705401	582	595	phencyclidine	Chemical	D010622
20705401	612	616	5-HT	Chemical	D012701
20705401	741	754	schizophrenia	Disease	D012559
20705401	801	805	5-HT	Chemical	D012701
20705401	856	875	psychotic disorders	Disease	D011605
20705401	893	908	methamphetamine	Chemical	D008694
20705401	910	914	METH	Chemical	D008694
20705401	924	933	psychosis	Disease	D011605
20705401	958	985	paranoid type schizophrenia	Disease	D012563
20705401	1049	1053	5-HT	Chemical	D012701
20705401	1072	1076	METH	Chemical	D008694
20705401	1085	1094	psychosis	Disease	D011605
20705401	1261	1265	METH	Chemical	D008694
20705401	1274	1283	psychosis	Disease	D011605
20705401	1412	1427	methamphetamine	Chemical	D008694
20705401	1488	1492	METH	Chemical	D008694
20705401	1501	1510	psychosis	Disease	D011605
20705401	1807	1811	METH	Chemical	D008694
20705401	1820	1829	psychosis	Disease	D011605
20705401	1924	1928	METH	Chemical	D008694
20705401	1937	1946	psychosis	Disease	D011605
20705401	CID	D008694	D011605

19105845|t|Effect of increasing intraperitoneal infusion rates on bupropion hydrochloride-induced seizures in mice.
19105845|a|BACKGROUND: It is not known if there is a relationship between input rate and incidence of bupropion-induced seizures. This is important, since different controlled release formulations of bupropion release the active drug at different rates. METHODS: We investigated the effect of varying the intraperitoneal infusion rates of bupropion HCl 120 mg/kg, a known convulsive dose 50 (CD50), on the incidence and severity of bupropion-induced convulsions in the Swiss albino mice. A total of 69 mice, approximately 7 weeks of age, and weighing 21.0 to 29.1 g were randomly assigned to bupropion HCl 120 mg/kg treatment by intraperitoneal (IP) administration in 7 groups (9 to 10 animals per group). Bupropion HCl was infused through a surgically implanted IP dosing catheter with infusions in each group of 0 min, 15 min, 30 min, 60 min, 90 min, 120 min, and 240 min. The number, time of onset, duration and the intensity of the convulsions or absence of convulsions were recorded. RESULTS: The results showed that IP administration of bupropion HCl 120 mg/kg by bolus injection induced convulsions in 6 out of 10 mice (60% of convulsing mice) in group 1. Logistic regression analysis revealed that infusion time was significant (p = 0.0004; odds ratio = 0.974) and increasing the IP infusion time of bupropion HCl 120 mg/kg was associated with a 91% reduced odds of convulsions at infusion times of 15 to 90 min compared to bolus injection. Further increase in infusion time resulted in further reduction in the odds of convulsions to 99.8% reduction at 240 min. CONCLUSION: In conclusion, the demonstration of an inverse relationship between infusion time of a fixed and convulsive dose of bupropion and the risk of convulsions in a prospective study is novel.
19105845	55	78	bupropion hydrochloride	Chemical	D016642
19105845	87	95	seizures	Disease	D012640
19105845	196	205	bupropion	Chemical	D016642
19105845	214	222	seizures	Disease	D012640
19105845	294	303	bupropion	Chemical	D016642
19105845	433	446	bupropion HCl	Chemical	D016642
19105845	466	476	convulsive	Disease	D012640
19105845	526	535	bupropion	Chemical	D016642
19105845	544	555	convulsions	Disease	D012640
19105845	686	699	bupropion HCl	Chemical	D016642
19105845	800	813	Bupropion HCl	Chemical	D016642
19105845	1030	1041	convulsions	Disease	D012640
19105845	1056	1067	convulsions	Disease	D012640
19105845	1137	1150	bupropion HCl	Chemical	D016642
19105845	1188	1199	convulsions	Disease	D012640
19105845	1402	1415	bupropion HCl	Chemical	D016642
19105845	1468	1479	convulsions	Disease	D012640
19105845	1622	1633	convulsions	Disease	D012640
19105845	1774	1784	convulsive	Disease	D012640
19105845	1793	1802	bupropion	Chemical	D016642
19105845	1819	1830	convulsions	Disease	D012640
19105845	CID	D016642	D012640

18657397|t|Detailed spectral profile analysis of penicillin-induced epileptiform activity in anesthetized rats.
18657397|a|Penicillin model is a widely used experimental model for epilepsy research. In the present study we aimed to portray a detailed spectral analysis of penicillin-induced epileptiform activity in comparison with basal brain activity in anesthetized Wistar rats. Male Wistar rats were anesthetized with i.p. urethane and connected to an electrocorticogram setup. After a short period of basal activity recording, epileptic focus was induced by injecting 400IU/2 microl penicillin-G potassium into the left lateral ventricle while the cortical activity was continuously recorded. Basal activity, latent period and the penicillin-induced epileptiform activity periods were then analyzed using both conventional methods and spectral analysis. Spectral analyses were conducted by dividing the whole spectrum into different frequency bands including delta, theta (slow and fast), alpha-sigma, beta (1 and 2) and gamma (1 and 2) bands. Our results show that the most affected frequency bands were delta, theta, beta-2 and gamma-2 bands during the epileptiform activity and there were marked differences in terms of spectral densities between three investigated episodes (basal activity, latent period and epileptiform activity). Our results may help to analyze novel data obtained using similar experimental models and the simple analysis method described here can be used in similar studies to investigate the basic neuronal mechanism of this or other types of experimental epilepsies.
18657397	38	48	penicillin	Chemical	D010406
18657397	57	78	epileptiform activity	Disease	D004827
18657397	101	111	Penicillin	Chemical	D010406
18657397	158	166	epilepsy	Disease	D004827
18657397	250	260	penicillin	Chemical	D010406
18657397	269	290	epileptiform activity	Disease	D004827
18657397	405	413	urethane	Chemical	D014520
18657397	510	519	epileptic	Disease	D004827
18657397	566	588	penicillin-G potassium	Chemical	D010400
18657397	714	724	penicillin	Chemical	D010406
18657397	733	754	epileptiform activity	Disease	D004827
18657397	1138	1159	epileptiform activity	Disease	D004827
18657397	1296	1317	epileptiform activity	Disease	D004827
18657397	1566	1576	epilepsies	Disease	D004827
18657397	CID	D010400	D004827

18363626|t|High dose dexmedetomidine as the sole sedative for pediatric MRI.
18363626|a|OBJECTIVE: This large-scale retrospective review evaluates the sedation profile of dexmedetomidine. AIM: To determine the hemodynamic responses, efficacy and adverse events associated with the use of high dose dexmedetomidine as the sole sedative for magnetic resonance imaging (MRI) studies. BACKGROUND: Dexmedetomidine has been used at our institution since 2005 to provide sedation for pediatric radiological imaging studies. Over time, an effective protocol utilizing high dose dexmedetomidine as the sole sedative agent has evolved. METHODS/MATERIALS: As part of the ongoing Quality Assurance process, data on all sedations are reviewed monthly and protocols modified as needed. Data were analyzed from all 747 consecutive patients who received dexmedetomidine for MRI sedation from April 2005 to April 2007. RESULTS: Since 2005, the 10-min loading dose of our dexmedetomidine protocol increased from 2 to 3 microg.kg(-1), and the infusion rate increased from 1 to 1.5 to 2 microg.kg(-1).h(-1). The current sedation protocol progressively increased the rate of successful sedation (able to complete the imaging study) when using dexmedetomidine alone from 91.8% to 97.6% (P = 0.009), reducing the requirement for adjuvant pentobarbital in the event of sedation failure with dexmedetomidine alone and decreased the mean recovery time by 10 min (P < 0.001). Although dexmedetomidine sedation was associated with a 16% incidence of bradycardia, all concomitant mean arterial blood pressures were within 20% of age-adjusted normal range and oxygen saturations were 95% or higher. CONCLUSION: Dexmedetomidine in high doses provides adequate sedation for pediatric MRI studies. While use of high dose dexmedetomidine is associated with decreases in heart rate and blood pressure outside the established 'awake' norms, this deviation is generally within 20% of norms, and is not associated with adverse sequelae. Dexmedetomidine is useful as the sole sedative for pediatric MRI.
18363626	10	25	dexmedetomidine	Chemical	D020927
18363626	149	164	dexmedetomidine	Chemical	D020927
18363626	276	291	dexmedetomidine	Chemical	D020927
18363626	371	386	Dexmedetomidine	Chemical	D020927
18363626	548	563	dexmedetomidine	Chemical	D020927
18363626	816	831	dexmedetomidine	Chemical	D020927
18363626	932	947	dexmedetomidine	Chemical	D020927
18363626	1200	1215	dexmedetomidine	Chemical	D020927
18363626	1293	1306	pentobarbital	Chemical	D010424
18363626	1345	1360	dexmedetomidine	Chemical	D020927
18363626	1436	1451	dexmedetomidine	Chemical	D020927
18363626	1500	1511	bradycardia	Disease	D001919
18363626	1608	1614	oxygen	Chemical	D010100
18363626	1659	1674	Dexmedetomidine	Chemical	D020927
18363626	1766	1781	dexmedetomidine	Chemical	D020927
18363626	1977	1992	Dexmedetomidine	Chemical	D020927
18363626	CID	D020927	D001919

16192988|t|Methamphetamine causes alterations in the MAP kinase-related pathways in the brains of mice that display increased aggressiveness.
16192988|a|Aggressive behaviors have been reported in patients who suffer from some psychiatric disorders, and are common in methamphetamine (METH) abusers. Herein, we report that multiple (but not single) injections of METH significantly increased aggressiveness in male CD-1 mice. This increase in aggressiveness was not secondary to METH-induced hyperactivity. Analysis of protein expression using antibody microarrays and Western blotting revealed differential changes in MAP kinase-related pathways after multiple and single METH injections. There were statistically significant (p<0.05) decreases in MEK1, Erk2p, GSK3alpha, 14-3-3e, and MEK7 in the striata of mice after multiple injections of METH. MEK1 was significantly decreased also after a single injection of METH, but to a much lesser degree than after multiple injections of METH. In the frontal cortex, there was a statistically significant decrease in GSK3alpha after multiple (but not single) injections of METH. These findings suggest that alterations in MAP kinase-related pathways in the prefronto-striatal circuitries might be involved in the manifestation of aggressive behaviors in mice.
16192988	0	15	Methamphetamine	Chemical	D008694
16192988	115	129	aggressiveness	Disease	D001523
16192988	131	151	Aggressive behaviors	Disease	D001523
16192988	204	225	psychiatric disorders	Disease	D001523
16192988	245	260	methamphetamine	Chemical	D008694
16192988	262	266	METH	Chemical	D008694
16192988	340	344	METH	Chemical	D008694
16192988	369	383	aggressiveness	Disease	D001523
16192988	420	434	aggressiveness	Disease	D001523
16192988	456	460	METH	Chemical	D008694
16192988	469	482	hyperactivity	Disease	D006948
16192988	650	654	METH	Chemical	D008694
16192988	820	824	METH	Chemical	D008694
16192988	892	896	METH	Chemical	D008694
16192988	960	964	METH	Chemical	D008694
16192988	1095	1099	METH	Chemical	D008694
16192988	1252	1272	aggressive behaviors	Disease	D001523
16192988	CID	D008694	D001523

16157917|t|Lamotrigine associated with exacerbation or de novo myoclonus in idiopathic generalized epilepsies.
16157917|a|Five patients with idiopathic generalized epilepsies (IGE) treated with lamotrigine (LTG) experienced exacerbation or de novo appearance of myoclonic jerks (MJ). In three patients, LTG exacerbated MJ in a dose-dependent manner with early aggravation during titration. MJ disappeared when LTG dose was decreased by 25 to 50%. In two patients, LTG exacerbated MJ in a delayed but more severe manner, with myoclonic status that only ceased after LTG withdrawal.
16157917	0	11	Lamotrigine	Chemical	C047781
16157917	52	61	myoclonus	Disease	D009207
16157917	65	98	idiopathic generalized epilepsies	Disease	C562694
16157917	119	152	idiopathic generalized epilepsies	Disease	C562694
16157917	154	157	IGE	Disease	C562694
16157917	172	183	lamotrigine	Chemical	C047781
16157917	185	188	LTG	Chemical	C047781
16157917	240	255	myoclonic jerks	Disease	D009207
16157917	257	259	MJ	Disease	D009207
16157917	281	284	LTG	Chemical	C047781
16157917	297	299	MJ	Disease	D009207
16157917	368	370	MJ	Disease	D009207
16157917	388	391	LTG	Chemical	C047781
16157917	442	445	LTG	Chemical	C047781
16157917	458	460	MJ	Disease	D009207
16157917	503	519	myoclonic status	Disease	D009207
16157917	543	546	LTG	Chemical	C047781
16157917	CID	C047781	D009207

16116131|t|rTMS of supplementary motor area modulates therapy-induced dyskinesias in Parkinson disease.
16116131|a|The neural mechanisms and circuitry involved in levodopa-induced dyskinesia are unclear. Using repetitive transcranial magnetic stimulation (rTMS) over the supplementary motor area (SMA) in a group of patients with advanced Parkinson disease, the authors investigated whether modulation of SMA excitability may result in a modification of a dyskinetic state induced by continuous apomorphine infusion. rTMS at 1 Hz was observed to markedly reduce drug-induced dyskinesias, whereas 5-Hz rTMS induced a slight but not significant increase.
16116131	59	70	dyskinesias	Disease	D004409
16116131	74	91	Parkinson disease	Disease	D010300
16116131	141	149	levodopa	Chemical	D007980
16116131	158	168	dyskinesia	Disease	D004409
16116131	317	334	Parkinson disease	Disease	D010300
16116131	434	444	dyskinetic	Disease	D004409
16116131	473	484	apomorphine	Chemical	D001058
16116131	540	564	drug-induced dyskinesias	Disease	D004409
16116131	CID	D007980	D004409

15930398|t|Assessment of the onset and persistence of amnesia during procedural sedation with propofol.
15930398|a|OBJECTIVES: To assess patients' ability to repeat and recall words presented to them while undergoing procedural sedation with propofol, and correlate their recall with their level of awareness as measured by bispectral index (BIS) monitoring. METHODS: This was a prospective, single-intervention study of consenting adult patients undergoing procedural sedation with propofol between December 28, 2002, and October 31, 2003. BIS monitoring was initiated starting 3 minutes before the procedure and continuing until the patient had regained baseline mental status. At 1-minute intervals during the procedural sedation, until the patient regained baseline mental status at the end of the procedure, a word from a standardized list was read aloud, and the patient was asked to immediately repeat the word to the investigator. The BIS score at the time the word was read and the patient's ability to repeat the word were recorded. After the procedure, the patient was asked to state all of the words from the list that he or she could recall, and to identify the last word recalled from prior to the start of the procedure and the first word recalled from after the procedure was completed. RESULTS: Seventy-five consenting patients were enrolled; one patient was excluded from data analysis for a protocol violation. No serious adverse events were noted during the procedural sedations. The mean (+/-standard deviation) time of data collection was 16.4 minutes (+/-7.1; range 5 to 34 minutes). The mean initial (preprocedure) BIS score was 97.1 (+/-2.3; range 92 to 99). The mean lowest BIS score occurring during these procedural sedations was 66.9 (+/-14.4; range 33 to 91). The mean lowest BIS score corresponding to the ability of the patient to immediately repeat words read from the list was 77.1 (95% CI = 74.3 to 80.0). The mean highest BIS score corresponding to the inability to repeat words was 81.5 (95% CI = 78.1 to 84.8). The mean BIS score corresponding to the last word recalled from prior to the initiation of the sedation was 96.7 (+/-2.4; range 84 to 98). The mean BIS score corresponding to the first word recalled after the procedure was completed was 91.2 (95% CI = 88.1 to 94.3). All patients recalled at least one word that had been read to them during the protocol. The mean lowest BIS score for any recalled word was 91.5 (+/-11.1; range 79 to 98), and no words were recalled when the corresponding BIS score was less than 90. CONCLUSIONS: There is a range of BIS scores during which sedated patients are able to repeat words read to them but are not able to subsequently recall these words. Furthermore, patients had no recall of words repeated prior to procedural sedation in BIS ranges associated with recall after procedural sedation, suggestive of retrograde amnesia.
15930398	43	50	amnesia	Disease	D000647
15930398	83	91	propofol	Chemical	D015742
15930398	220	228	propofol	Chemical	D015742
15930398	461	469	propofol	Chemical	D015742
15930398	1967	1992	inability to repeat words	Disease	D000647
15930398	2870	2888	retrograde amnesia	Disease	D000648
15930398	CID	D015742	D000647

15867025|t|Assessment of perinatal hepatitis B and rubella prevention in New Hampshire delivery hospitals.
15867025|a|OBJECTIVE: To evaluate current performance on recommended perinatal hepatitis B and rubella prevention practices in New Hampshire. METHODS: Data were extracted from 2021 paired mother-infant records for the year 2000 birth cohort in New Hampshire's 25 delivery hospitals. Assessment was done on the following: prenatal screening for hepatitis B and rubella, administration of the hepatitis B vaccine birth dose to all infants, administration of hepatitis B immune globulin to infants who were born to hepatitis B surface antigen-positive mothers, rubella immunity, and administration of in-hospital postpartum rubella vaccine to rubella nonimmune women. RESULTS: Prenatal screening rates for hepatitis B (98.8%) and rubella (99.4%) were high. Hepatitis B vaccine birth dose was administered to 76.2% of all infants. All infants who were born to hepatitis B surface antigen-positive mothers also received hepatitis B immune globulin. Multivariate logistic regression showed that the month of delivery and infant birth weight were independent predictors of hepatitis B vaccination. The proportion of infants who were vaccinated in January and February 2000 (48.5% and 67.5%, respectively) was less than any other months, whereas the proportion who were vaccinated in December 2000 (88.2%) was the highest. Women who were born between 1971 and 1975 had the highest rate of rubella nonimmunity (9.5%). In-hospital postpartum rubella vaccine administration was documented for 75.6% of nonimmune women. CONCLUSION: This study documents good compliance in New Hampshire's birthing hospitals with national guidelines for perinatal hepatitis B and rubella prevention and highlights potential areas for improvement.
15867025	24	35	hepatitis B	Disease	D006509
15867025	40	47	rubella	Disease	D012409
15867025	164	175	hepatitis B	Disease	D006509
15867025	180	187	rubella	Disease	D012409
15867025	429	440	hepatitis B	Disease	D006509
15867025	445	452	rubella	Disease	D012409
15867025	476	487	hepatitis B	Disease	D006509
15867025	541	552	hepatitis B	Disease	D006509
15867025	597	624	hepatitis B surface antigen	Chemical	D006514
15867025	643	650	rubella	Disease	D012409
15867025	706	713	rubella	Disease	D012409
15867025	725	732	rubella	Disease	D012409
15867025	788	799	hepatitis B	Disease	D006509
15867025	812	819	rubella	Disease	D012409
15867025	839	850	Hepatitis B	Disease	D006509
15867025	941	968	hepatitis B surface antigen	Chemical	D006514
15867025	1000	1011	hepatitis B	Disease	D006509
15867025	1151	1162	hepatitis B	Disease	D006509
15867025	1466	1473	rubella	Disease	D012409
15867025	1517	1524	rubella	Disease	D012409
15867025	1719	1730	hepatitis B	Disease	D006509
15867025	1735	1742	rubella	Disease	D012409
15867025	CID	D006514	D006509

14975762|t|Expression of p300 protects cardiac myocytes from apoptosis in vivo.
14975762|a|Doxorubicin is an anti-tumor agent that represses cardiac-specific gene expression and induces myocardial cell apoptosis. Doxorubicin depletes cardiac p300, a transcriptional coactivator that is required for the maintenance of the differentiated phenotype of cardiac myocytes. However, the role of p300 in protection against doxorubicin-induced apoptosis is unknown. Transgenic mice overexpressing p300 in the heart and wild-type mice were subjected to doxorubicin treatment. Compared with wild-type mice, transgenic mice exhibited higher survival rate as well as more preserved left ventricular function and cardiac expression of alpha-sarcomeric actin. Doxorubicin induced myocardial cell apoptosis in wild-type mice but not in transgenic mice. Expression of p300 increased the cardiac level of bcl-2 and mdm-2, but not that of p53 or other members of the bcl-2 family. These findings demonstrate that overexpression of p300 protects cardiac myocytes from doxorubicin-induced apoptosis and reduces the extent of acute heart failure in adult mice in vivo.
14975762	69	80	Doxorubicin	Chemical	D004317
14975762	92	97	tumor	Disease	D009369
14975762	191	202	Doxorubicin	Chemical	D004317
14975762	394	405	doxorubicin	Chemical	D004317
14975762	522	533	doxorubicin	Chemical	D004317
14975762	724	735	Doxorubicin	Chemical	D004317
14975762	1027	1038	doxorubicin	Chemical	D004317
14975762	1089	1102	heart failure	Disease	D006333
14975762	CID	D004317	D006333

14736955|t|Mitochondrial DNA and its respiratory chain products are defective in doxorubicin nephrosis.
14736955|a|BACKGROUND: Doxorubicin induces a self-perpetuating nephropathy characterized by early glomerular and late-onset tubular lesions in rats. We investigated the potential role of mitochondrial injury in the onset of these lesions. METHODS: Rats were treated with intravenous doxorubicin (1 mg kg(-1) week(-1)) for 7 weeks and were sacrificed either 1 week ('short-term') or 30 weeks ('long-term') following the last dose. Additional rats received a single dose either 6 days or 2 h prior to euthanasia. All rats were killed at 48 weeks of age. Glomerular and tubular injury was monitored and correlated to the activity or expression of respiratory chain components. Finally, we quantified both nuclear and mitochondrial DNA (mtDNA) as well as superoxide production and the 4834 base pair 'common' mtDNA deletion. RESULTS: The 'long-term' group had significant glomerular and tubular lesions, depressed activities of mtDNA-encoded NADH dehydrogenase and cytochrome-c oxidase (COX) and increased citrate synthase activity. In addition, expression of the mtDNA-encoded COX subunit I was reduced and mtDNA levels were decreased. In 'short-term' rats, there were fewer tubular lesions, but similar numbers of glomerular lesions activity. Among all animals, glomerular and tubular injury were inversely correlated with mtDNA levels, mtDNA-encoded respiratory chain activities and with the expression of the mtDNA-encoded respiratory chain subunit COX-I. Injury was positively correlated with superoxide production and the activities of nucleus-encoded mitochondrial or cytoplasmic enzymes. Kidneys from the 'long-term' group showed more mtDNA deletions than in 'short-term' animals and these were not observed in the other groups. CONCLUSIONS: These results suggest an important role for quantitative and qualitative mtDNA alterations through the reduction of mtDNA-encoded respiratory chain function and induction of superoxide in doxorubicin-induced renal lesions.
14736955	70	81	doxorubicin	Chemical	D004317
14736955	82	91	nephrosis	Disease	D009401
14736955	105	116	Doxorubicin	Chemical	D004317
14736955	145	156	nephropathy	Disease	D007674
14736955	180	221	glomerular and late-onset tubular lesions	Disease	D007674
14736955	269	289	mitochondrial injury	Disease	D028361
14736955	365	376	doxorubicin	Chemical	D004317
14736955	634	663	Glomerular and tubular injury	Disease	D007674
14736955	833	843	superoxide	Chemical	D013481
14736955	950	980	glomerular and tubular lesions	Disease	D007674
14736955	1084	1091	citrate	Chemical	C102006
14736955	1254	1269	tubular lesions	Disease	D007674
14736955	1294	1312	glomerular lesions	Disease	D007674
14736955	1342	1371	glomerular and tubular injury	Disease	D007674
14736955	1576	1586	superoxide	Chemical	D013481
14736955	2002	2012	superoxide	Chemical	D013481
14736955	2016	2027	doxorubicin	Chemical	D004317
14736955	2036	2049	renal lesions	Disease	D007674
14736955	CID	D004317	D009401

11573852|t|Amphotericin B-induced seizures in a patient with AIDS.
11573852|a|OBJECTIVE: To report a case of multiple episodes of seizure activity in an AIDS patent following amphotericin B infusion. CASE SUMMARY: A 46-year-old African-American man experienced recurrent grand mal seizures during intravenous infusion of amphotericin B, then petit mal seizures as the infusion was stopped and the drug concentrations decreased with time. The patients concurrent medications included didanosine, hydroxyzine, promethazine, hydrocortisone, and prochlorperazine. Despite administration of phenytoin and lorazepam, the seizures persisted and occurred only during amphotercin B administration. DISCUSSION: AIDS and cryptococcal meningitis, both of which the patient had, can potentially cause seizures. The patient had a history of alcohol abuse; alcohol intake as well as withdrawal can also cause seizures. Didanosine also has a potential for inducing seizures. However, these other potential causes of seizure were ruled out. The time course of events suggested that amphotericin B was the cause of the seizures in this AIDS patient. CONCLUSIONS: Amphotericin B seems to be the probable cause of the seizures. To date, only three cases of seizures associated with amphotericin B have been reported in the literature, but healthcare providers should be aware of the potential for this rare adverse effect.
11573852	0	14	Amphotericin B	Chemical	D000666
11573852	23	31	seizures	Disease	D012640
11573852	50	54	AIDS	Disease	D000163
11573852	108	115	seizure	Disease	D012640
11573852	131	135	AIDS	Disease	D000163
11573852	153	167	amphotericin B	Chemical	D000666
11573852	249	267	grand mal seizures	Disease	D004830
11573852	299	313	amphotericin B	Chemical	D000666
11573852	330	338	seizures	Disease	D012640
11573852	461	471	didanosine	Chemical	D016049
11573852	473	484	hydroxyzine	Chemical	D006919
11573852	486	498	promethazine	Chemical	D011398
11573852	500	514	hydrocortisone	Chemical	D006854
11573852	520	536	prochlorperazine	Chemical	D011346
11573852	564	573	phenytoin	Chemical	D010672
11573852	578	587	lorazepam	Chemical	D008140
11573852	593	601	seizures	Disease	D012640
11573852	637	650	amphotercin B	Chemical	D000666
11573852	679	683	AIDS	Disease	D000163
11573852	688	711	cryptococcal meningitis	Disease	D016919
11573852	766	774	seizures	Disease	D012640
11573852	805	818	alcohol abuse	Disease	D000437
11573852	820	827	alcohol	Chemical	D000431
11573852	872	880	seizures	Disease	D012640
11573852	882	892	Didanosine	Chemical	D016049
11573852	927	935	seizures	Disease	D012640
11573852	978	985	seizure	Disease	D012640
11573852	1043	1057	amphotericin B	Chemical	D000666
11573852	1079	1087	seizures	Disease	D012640
11573852	1096	1100	AIDS	Disease	D000163
11573852	1123	1137	Amphotericin B	Chemical	D000666
11573852	1176	1184	seizures	Disease	D012640
11573852	1215	1223	seizures	Disease	D012640
11573852	1240	1254	amphotericin B	Chemical	D000666
11573852	CID	D000666	D012640

9875685|t|Therapeutic drug monitoring of tobramycin: once-daily versus twice-daily dosage schedules.
9875685|a|OBJECTIVE: To evaluate the effect of dosage regimen (once-daily vs. twice-daily) of tobramicyn on steady-state serum concentrations and toxicity. MATERIALS AND METHODS: Patients undergoing treatment with i.v. tobramycin (4 mg/kg/day) were randomised to two groups. Group OD (n = 22) received a once-daily dose of tobramycin and group TD (n = 21) received the same dose divided into two doses daily. Tobramycin serum concentrations (peak and trough) were measured by enzyme multiplied immunoassay. The renal and auditory functions of the patients were monitored before, during and immediately after treatment. RESULTS: The two groups were comparable with respect to sex, age, body weight and renal function. No statistically significant differences were found in mean daily dose, duration of treatment, or cumulative dose. Trough concentrations were < 2 g/ml in the two groups (100%). Peak concentrations were > 6 microg/ml in 100% of the OD group and in 67% of the TD group (P< 0.01). Mean peak concentrations were markedly different: 11.00+/-2.89 microg/ml in OD vs. 6.53+/-1.45 microg/ml in TD (P< 0.01). The pharmacokinetics parameters were: Ke, (0.15+/-0.03/h in OD vs. 0.24+/-0.06/h in TD), t1/2, (4.95+/-1.41 h in OD vs. 3.07+/-0.71 h in TD), Vd (0.35+/-0.11 l/kg in OD vs. 0.33+/-0.09 l/kg in TD), Cl (0.86+/-0.29 ml/min/kg in OD vs. 1.28+/-0.33 ml/min/kg in TD). Increased serum creatinine was observed in 73% of patients in OD versus 57% of patients in TD, without evidence of nephrotoxicity. In TD group, three patients developed decreased auditory function, of which one presented with an auditory loss of -30 dB, whereas in the OD group only one patient presented decreased auditory function. CONCLUSION: This small study suggests that a once-daily dosing regimen of tobramycin is at least as effective as and is no more and possibly less toxic than the twice-daily regimen. Using a single-dose therapy, peak concentration determination is not necessary, only trough samples should be monitored to ensure levels below 2 microg/ml.
9875685	31	41	tobramycin	Chemical	D014031
9875685	175	185	tobramicyn	Chemical	D014031
9875685	227	235	toxicity	Disease	D064420
9875685	300	310	tobramycin	Chemical	D014031
9875685	404	414	tobramycin	Chemical	D014031
9875685	490	500	Tobramycin	Chemical	D014031
9875685	1478	1488	creatinine	Chemical	D003404
9875685	1577	1591	nephrotoxicity	Disease	D007674
9875685	1631	1658	decreased auditory function	Disease	D034381
9875685	1691	1704	auditory loss	Disease	D034381
9875685	1767	1794	decreased auditory function	Disease	D034381
9875685	1870	1880	tobramycin	Chemical	D014031
9875685	CID	D014031	D034381

9848575|t|Chronic effects of a novel synthetic anthracycline derivative (SM-5887) on normal heart and doxorubicin-induced cardiomyopathy in beagle dogs.
9848575|a|This study was designed to investigate the chronic cardiotoxic potential of SM-5887 and a possible deteriorating effect of SM-5887 on low-grade cardiotoxicity pre-induced by doxorubicin in beagle dogs. In the chronic treatment, beagle dogs of each sex were given intravenously once every 3 weeks, either a sublethal dose of doxorubicin (1.5 mg/kg) or SM-5887 (2.5 mg/kg). The experiment was terminated 3 weeks after the ninth dosing. Animals which received over six courses of doxorubicin demonstrated the electrocardiogram (ECG) changes, decrease of blood pressure and high-grade histopathological cardiomyopathy, while animals which were terminally sacrificed after the SM-5887 administration did not show any changes in ECG, blood pressure and histopathological examinations. To examine a possibly deteriorating cardiotoxic effect of SM-5887, low-grade cardiomyopathy was induced in dogs by four courses of doxorubicin (1.5 mg/kg). Nine weeks after pre-treatment, dogs were given four courses of either doxorubicin (1.5 mg/kg) or SM-5887 (2.5 mg/kg) once every 3 weeks. The low-grade cardiotoxic changes were enhanced by the additional doxorubicin treatment. On the contrary, the SM-5887 treatment did not progress the grade of cardiomyopathy. In conclusion, SM-5887 does not have any potential of chronic cardiotoxicity and deteriorating effect on doxorubicin-induced cardiotoxicity in dogs.
9848575	37	50	anthracycline	Chemical	D018943
9848575	63	70	SM-5887	Chemical	C055866
9848575	92	103	doxorubicin	Chemical	D004317
9848575	112	126	cardiomyopathy	Disease	D009202
9848575	194	205	cardiotoxic	Disease	D066126
9848575	219	226	SM-5887	Chemical	C055866
9848575	266	273	SM-5887	Chemical	C055866
9848575	287	301	cardiotoxicity	Disease	D066126
9848575	317	328	doxorubicin	Chemical	D004317
9848575	467	478	doxorubicin	Chemical	D004317
9848575	494	501	SM-5887	Chemical	C055866
9848575	620	631	doxorubicin	Chemical	D004317
9848575	742	756	cardiomyopathy	Disease	D009202
9848575	815	822	SM-5887	Chemical	C055866
9848575	958	969	cardiotoxic	Disease	D066126
9848575	980	987	SM-5887	Chemical	C055866
9848575	999	1013	cardiomyopathy	Disease	D009202
9848575	1053	1064	doxorubicin	Chemical	D004317
9848575	1149	1160	doxorubicin	Chemical	D004317
9848575	1176	1183	SM-5887	Chemical	C055866
9848575	1230	1241	cardiotoxic	Disease	D066126
9848575	1282	1293	doxorubicin	Chemical	D004317
9848575	1326	1333	SM-5887	Chemical	C055866
9848575	1374	1388	cardiomyopathy	Disease	D009202
9848575	1405	1412	SM-5887	Chemical	C055866
9848575	1452	1466	cardiotoxicity	Disease	D066126
9848575	1495	1506	doxorubicin	Chemical	D004317
9848575	1515	1529	cardiotoxicity	Disease	D066126
9848575	CID	D004317	D009202

9321531|t|Posteroventral medial pallidotomy in advanced Parkinson's disease.
9321531|a|BACKGROUND: Posteroventral medial pallidotomy sometimes produces striking improvement in patients with advanced Parkinson's disease, but the studies to date have involved small numbers of patients and short-term follow-up. METHODS: Forty patients with Parkinson's disease underwent serial, detailed assessments both after drug withdrawal ("off" period) and while taking their optimal medical regimens ("on" period). All patients were examined preoperatively and 39 were examined at six months; 27 of the patients were also examined at one year, and 11 at two years. RESULTS: The percent improvements at six months were as follows: off-period score for overall motor function, 28 percent (95 percent confidence interval, 19 to 38 percent), with most of the improvement in the contralateral limbs; off-period score for activities of daily living, 29 percent (95 percent confidence interval, 19 to 39 percent); on-period score for contralateral dyskinesias, 82 percent (95 percent confidence interval, 72 to 91 percent); and on-period score for ipsilateral dyskinesias, 44 percent (95 percent confidence interval, 29 to 59 percent). The improvements in dyskinesias and the total scores for off-period parkinsonism, contralateral bradykinesia, and rigidity were sustained in the 11 patients examined at two years. The improvement in ipsilateral dyskinesias was lost after one year, and the improvements in postural stability and gait lasted only three to six months. Approximately half the patients who had been dependent on assistance in activities of daily living in the off period before surgery became independent after surgery. The complications of surgery were generally well tolerated, and there were no significant changes in the use of medication. CONCLUSIONS: In late-stage Parkinson's disease, pallidotomy significantly reduces levodopa-induced dyskinesias and off-period disability. Much of the benefit is sustained at two years, although some improvements, such as those on the ipsilateral side and in axial symptoms, wane within the first year. The on-period symptoms that are resistant to dopaminergic therapy do not respond to pallidotomy.
9321531	46	65	Parkinson's disease	Disease	D010300
9321531	179	198	Parkinson's disease	Disease	D010300
9321531	319	338	Parkinson's disease	Disease	D010300
9321531	1009	1020	dyskinesias	Disease	D004409
9321531	1121	1132	dyskinesias	Disease	D004409
9321531	1217	1228	dyskinesias	Disease	D004409
9321531	1265	1277	parkinsonism	Disease	D010300
9321531	1293	1305	bradykinesia	Disease	D018476
9321531	1311	1319	rigidity	Disease	D009127
9321531	1408	1419	dyskinesias	Disease	D004409
9321531	1847	1866	Parkinson's disease	Disease	D010300
9321531	1902	1910	levodopa	Chemical	D007980
9321531	1919	1930	dyskinesias	Disease	D004409
9321531	CID	D007980	D004409

9305828|t|Neuropeptide-Y immunoreactivity in the pilocarpine model of temporal lobe epilepsy.
9305828|a|Neuropeptide-Y (NPY) is expressed by granule cells and mossy fibres of the hippocampal dentate gyrus during experimental temporal lobe epilepsy (TLE). This expression may represent an endogenous damping mechanism since NPY has been shown to block seizure-like events following high-frequency stimulation in hippocampal slices. The pilocarpine (PILO) model of epilepsy is characterized by an acute period of status epilepticus followed by spontaneous recurrent seizures and related brain damage. We report peroxidase-antiperoxidase immunostaining for NPY in several brain regions in this model. PILO-injected animals exhibited NPY immunoreactivity in the region of the mossy fibre terminals, in the dentate gyrus inner molecular layer and, in a few cases, within presumed granule cells. NPY immunoreactivity was also dramatically changed in the entorhinal cortex, amygdala and sensorimotor areas. In addition, PILO injected animals exhibited a reduction in the number of NPY-immunoreactive interneurons compared with controls. The results demonstrate that changes in NPY expression, including expression in the granule cells and mossy fibres and the loss of vulnerable NPY neurons, are present in the PILO model of TLE. However, the significance of this changed synthesis of NPY remains to be determined.
9305828	39	50	pilocarpine	Chemical	D010862
9305828	60	82	temporal lobe epilepsy	Disease	D004833
9305828	205	227	temporal lobe epilepsy	Disease	D004833
9305828	229	232	TLE	Disease	D004833
9305828	331	338	seizure	Disease	D012640
9305828	415	426	pilocarpine	Chemical	D010862
9305828	428	432	PILO	Chemical	D010862
9305828	443	451	epilepsy	Disease	D004827
9305828	491	509	status epilepticus	Disease	D013226
9305828	544	552	seizures	Disease	D012640
9305828	565	577	brain damage	Disease	D001930
9305828	678	682	PILO	Chemical	D010862
9305828	993	997	PILO	Chemical	D010862
9305828	1284	1288	PILO	Chemical	D010862
9305828	1298	1301	TLE	Disease	D004833
9305828	CID	D010862	D004833

9041081|t|Effect of myopic excimer laser photorefractive keratectomy on the electrophysiologic function of the retina and optic nerve.
9041081|a|PURPOSE: To assess by electrophysiologic testing the effect of photorefractive keratectomy (PRK) on the retina and optic nerve. SETTING: Eye Clinic, S. Salvatore Hospital, L'Aquila University, Italy. METHODS: Standard pattern electroretinograms (P-ERGs) and standard pattern visual evoked potentials (P-VEPs) were done in 25 eyes of 25 patients who had myopic PRK for an attempted correction between 5.00 and 15.00 diopters (D) (mean 8.00 D). Testing was done preoperatively and 3, 6, 12, and 18 months postoperatively. The contralateral eyes served as controls. During the follow-up, 3 patients (12%) developed steroid-induced elevated intraocular pressure (IOP) that resolved after corticosteroid therapy was discontinued. RESULTS: No statistically significant differences were seen between treated and control eyes nor between treated eyes preoperatively and postoperatively. CONCLUSION: Myopic excimer laser PRK did not seem to affect the posterior segment. The transient steroid-induced IOP rise did not seem to cause functional impairment.
9041081	737	744	steroid	Chemical	D013256
9041081	753	782	elevated intraocular pressure	Disease	D009798
9041081	809	823	corticosteroid	Chemical	D000305
9041081	1101	1108	steroid	Chemical	D013256
9041081	1117	1125	IOP rise	Disease	D009798
9041081	CID	D000305	D009798

8305357|t|Liposomal daunorubicin in advanced Kaposi's sarcoma: a phase II study.
8305357|a|We report a non-randomized Phase II clinical trial to assess the efficacy and safety of liposomal daunorubicin (DaunoXome) in the treatment of AIDS related Kaposi's sarcoma. Eleven homosexual men with advanced Kaposi's sarcoma were entered in the trial. Changes in size, colour and associated oedema of selected 'target' lesions were measured. Clinical, biochemical and haematological toxicities were assessed. Ten subjects were evaluated. A partial response was achieved in four, of whom two subsequently relapsed. Stabilization of Kaposi's sarcoma occurred in the remaining six, maintained until the end of the trial period in four. The drug was generally well tolerated, with few mild symptoms of toxicity. The main problem encountered was haematological toxicity, with three subjects experiencing severe neutropenia (neutrophil count < 0.5 x 10(9)/l). There was no evidence of cardiotoxicity. In this small patient sample, liposomal daunorubicin was an effective and well tolerated agent in the treatment of Kaposi's sarcoma.
8305357	10	22	daunorubicin	Chemical	D003630
8305357	35	51	Kaposi's sarcoma	Disease	D012514
8305357	169	181	daunorubicin	Chemical	D003630
8305357	214	218	AIDS	Disease	D000163
8305357	227	243	Kaposi's sarcoma	Disease	D012514
8305357	281	297	Kaposi's sarcoma	Disease	D012514
8305357	364	370	oedema	Disease	D004487
8305357	456	466	toxicities	Disease	D064420
8305357	604	620	Kaposi's sarcoma	Disease	D012514
8305357	771	779	toxicity	Disease	D064420
8305357	829	837	toxicity	Disease	D064420
8305357	879	890	neutropenia	Disease	D009503
8305357	952	966	cardiotoxicity	Disease	D066126
8305357	1008	1020	daunorubicin	Chemical	D003630
8305357	1083	1099	Kaposi's sarcoma	Disease	D012514
8305357	CID	D003630	D009503

8012887|t|Failure of ancrod in the treatment of heparin-induced arterial thrombosis.
8012887|a|The morbidity and mortality associated with heparin-induced thrombosis remain high despite numerous empirical therapies. Ancrod has been used successfully for prophylaxis against development of thrombosis in patients with heparin induced platelet aggregation who require brief reexposure to heparin, but its success in patients who have developed the thrombosis syndrome is not well defined. The authors present a case of failure of ancrod treatment in a patient with heparin-induced thrombosis.
8012887	38	45	heparin	Chemical	D006493
8012887	63	73	thrombosis	Disease	D013927
8012887	119	126	heparin	Chemical	D006493
8012887	135	145	thrombosis	Disease	D013927
8012887	269	279	thrombosis	Disease	D013927
8012887	297	304	heparin	Chemical	D006493
8012887	313	333	platelet aggregation	Disease	D001791
8012887	366	373	heparin	Chemical	D006493
8012887	426	436	thrombosis	Disease	D013927
8012887	543	550	heparin	Chemical	D006493
8012887	559	569	thrombosis	Disease	D013927
8012887	CID	D006493	D013927

7651879|t|Seizure after flumazenil administration in a pediatric patient.
7651879|a|Flumazenil is a benzodiazepine receptor antagonist used to reverse sedation and respiratory depression induced by benzodiazepines. Seizures and cardiac arrhythmias have complicated its use in adult patients. Overdose patients who have coingested tricyclic antidepressants have a higher risk of these complications. Little information exists concerning adverse effects of flumazenil in children. We report the occurrence of a generalized tonic-clonic seizure in a pediatric patient following the administration of flumazenil.
7651879	0	7	Seizure	Disease	D012640
7651879	14	24	flumazenil	Chemical	D005442
7651879	64	74	Flumazenil	Chemical	D005442
7651879	80	94	benzodiazepine	Chemical	D001569
7651879	144	166	respiratory depression	Disease	D012131
7651879	178	193	benzodiazepines	Chemical	D001569
7651879	195	203	Seizures	Disease	D012640
7651879	208	227	cardiac arrhythmias	Disease	D001145
7651879	272	280	Overdose	Disease	D062787
7651879	435	445	flumazenil	Chemical	D005442
7651879	501	521	tonic-clonic seizure	Disease	D012640
7651879	577	587	flumazenil	Chemical	D005442
7651879	CID	D005442	D012640

3015327|t|Remodelling of nerve structure in experimental isoniazid neuropathy in the rat.
3015327|a|The neuropathy caused by a single dose of isoniazid in rats was studied with a computer-assisted morphometric method. Scatter diagrams of the g ratio (quotient fibre diameter/axon diameter) define regenerating fibres as a distinct population, distinguishable from the surviving fibres by reduced sheath thickness and reduced axon calibre. There was also evidence of a subtle direct toxic effect on the entire fibre population, causing axon shrinkage masked by readjustment of the myelin sheath.
3015327	47	56	isoniazid	Chemical	D007538
3015327	57	67	neuropathy	Disease	D009422
3015327	84	94	neuropathy	Disease	D009422
3015327	122	131	isoniazid	Chemical	D007538
3015327	CID	D007538	D009422

2980315|t|Selective injection of iopentol, iohexol and metrizoate into the left coronary artery of the dog. Induction of ventricular fibrillation and decrease of aortic pressure.
2980315|a|In twenty beagle dogs selective injections were made into the left coronary artery with iopentol, iohexol and metrizoate in doses of 4 ml, 8 ml and 16 ml. Thirty-six iopentol injections, 35 iohexol injections and 37 metrizoate injections were made. Frequencies of ventricular fibrillation were significantly lower (p less than 0.05) after iopentol (0%) and iohexol (3%) than after metrizoate (22%). Iopentol and iohexol also produced significantly less decrease in aortic blood pressure than metrizoate at the different doses.
2980315	23	31	iopentol	Chemical	C053571
2980315	33	40	iohexol	Chemical	D007472
2980315	45	55	metrizoate	Chemical	D008794
2980315	111	135	ventricular fibrillation	Disease	D014693
2980315	257	265	iopentol	Chemical	C053571
2980315	267	274	iohexol	Chemical	D007472
2980315	279	289	metrizoate	Chemical	D008794
2980315	335	343	iopentol	Chemical	C053571
2980315	359	366	iohexol	Chemical	D007472
2980315	385	395	metrizoate	Chemical	D008794
2980315	433	457	ventricular fibrillation	Disease	D014693
2980315	508	516	iopentol	Chemical	C053571
2980315	526	533	iohexol	Chemical	D007472
2980315	550	560	metrizoate	Chemical	D008794
2980315	568	576	Iopentol	Chemical	C053571
2980315	581	588	iohexol	Chemical	D007472
2980315	661	671	metrizoate	Chemical	D008794
2980315	CID	D008794	D014693

2819587|t|Magnetic resonance imaging of cerebral venous thrombosis secondary to "low-dose" birth control pills.
2819587|a|The clinical and radiographic features of cerebral deep venous thrombosis in a 21-year-old white woman are presented. This nulliparous patient presented with relatively mild clinical symptoms and progressing mental status changes. The only known risk factor was "low-dose" oral contraceptive pills. The magnetic resonance image (MRI) showed increased signal intensity from the internal cerebral veins, vein of Galen, and straight sinus. The diagnosis was confirmed by arterial angiography.
2819587	39	56	venous thrombosis	Disease	D020246
2819587	153	175	deep venous thrombosis	Disease	D020246
2819587	375	393	oral contraceptive	Chemical	D003276
2819587	CID	D003276	D020246

1564236|t|Relation of perfusion defects observed with myocardial contrast echocardiography to the severity of coronary stenosis: correlation with thallium-201 single-photon emission tomography.
1564236|a|It has been previously shown that myocardial contrast echocardiography is a valuable technique for delineating regions of myocardial underperfusion secondary to coronary occlusion and to critical coronary stenoses in the presence of hyperemic stimulation. The aim of this study was to determine whether myocardial contrast echocardiography performed with a stable solution of sonicated albumin could detect regions of myocardial underperfusion resulting from various degrees of coronary stenosis. The perfusion defect produced in 16 open chest dogs was compared with the anatomic area at risk measured by the postmortem dual-perfusion technique and with thallium-201 single-photon emission tomography (SPECT). During a transient (20-s) coronary occlusion, a perfusion defect was observed with contrast echocardiography in 14 of the 15 dogs in which the occlusion was produced. The perfusion defect correlated significantly with the anatomic area at risk (r = 0.74; p less than 0.002). During dipyridamole-induced hyperemia, 12 of the 16 dogs with a partial coronary stenosis had a visible area of hypoperfusion by contrast echocardiography. The four dogs without a perfusion defect had a stenosis that resulted in a mild (0% to 50%) reduction in dipyridamole-induced hyperemia. The size of the perfusion defect during stenosis correlated significantly with the anatomic area at risk (r = 0.61; p = 0.02). Thallium-201 SPECT demonstrated a perfusion defect in all 14 dogs analyzed during dipyridamole-induced hyperemia; the size of the perfusion defect correlated with the anatomic area at risk (r = 0.58; p less than 0.03) and with the perfusion defect by contrast echocardiography (r = 0.58; p less than 0.03). Thus, myocardial contrast echocardiography can be used to visualize and quantitate the amount of jeopardized myocardium during moderate to severe degrees of coronary stenosis. The results obtained show a correlation with the anatomic area at risk similar to that obtained with thallium-201 SPECT.
1564236	100	117	coronary stenosis	Disease	D023921
1564236	136	144	thallium	Chemical	D013793
1564236	345	363	coronary occlusion	Disease	D054059
1564236	380	397	coronary stenoses	Disease	D023921
1564236	417	426	hyperemic	Disease	D006940
1564236	662	679	coronary stenosis	Disease	D023921
1564236	838	846	thallium	Chemical	D013793
1564236	920	938	coronary occlusion	Disease	D054059
1564236	1176	1188	dipyridamole	Chemical	D004176
1564236	1197	1206	hyperemia	Disease	D006940
1564236	1241	1258	coronary stenosis	Disease	D023921
1564236	1430	1442	dipyridamole	Chemical	D004176
1564236	1451	1460	hyperemia	Disease	D006940
1564236	1589	1597	Thallium	Chemical	D013793
1564236	1671	1683	dipyridamole	Chemical	D004176
1564236	1692	1701	hyperemia	Disease	D006940
1564236	2053	2070	coronary stenosis	Disease	D023921
1564236	2173	2181	thallium	Chemical	D013793
1564236	CID	D004176	D006940

1300436|t|Potential deleterious effect of furosemide in radiocontrast nephropathy.
1300436|a|The purpose of the study was to determine the efficacy of furosemide in addition to intravenous fluids in the prevention of radiocontrast nephropathy. 18 patients, referred to a radiocontrast study, considered at risk because of preexisting renal insufficiency, were enrolled in a prospective, randomized, controlled trial, performed at the secondary care center of a 1,100-bed private university hospital. In addition to fluids, the treatment group received furosemide (mean dose 110 mg) intravenously 30 min prior to the injection of contrast material. The control group received fluids (mean 3 liters). Radiological studies were mostly angiographies performed with both ionic and non-ionic contrast material, at an average dose of 245 ml. Renal function significantly deteriorated in the group pretreated with furosemide (p < 0.005 by ANOVA), with a rise in serum creatinine from 145 +/- 13 to 182 +/- 16 mumol/l at 24 h, while no change occurred in the control group (from 141 +/- 6 to 142 +/- 7 mumol/l). Renal failure was associated with weight loss in the furosemide-treated group. Furosemide may be deleterious in the prevention of radiocontrast nephropathy.
1300436	32	42	furosemide	Chemical	D005665
1300436	60	71	nephropathy	Disease	D007674
1300436	131	141	furosemide	Chemical	D005665
1300436	211	222	nephropathy	Disease	D007674
1300436	314	333	renal insufficiency	Disease	D051437
1300436	532	542	furosemide	Chemical	D005665
1300436	815	856	Renal function significantly deteriorated	Disease	D058186
1300436	886	896	furosemide	Chemical	D005665
1300436	940	950	creatinine	Chemical	D003404
1300436	1083	1096	Renal failure	Disease	D051437
1300436	1117	1128	weight loss	Disease	D015431
1300436	1136	1146	furosemide	Chemical	D005665
1300436	1162	1172	Furosemide	Chemical	D005665
1300436	1227	1238	nephropathy	Disease	D007674
1300436	CID	D005665	D058186

1141447|t|The renal pathology in a case of lithium-induced diabetes insipidus.
1141447|a|A case of lithium-induced diabetes insipidus is reported. At necropsy microscopy shoed unique and extensive damage to cells lining the distal nephron. It is suggested that these changes represent a specific toxic effect of lithium, reported here for the first time in man.
1141447	33	40	lithium	Chemical	D008094
1141447	49	67	diabetes insipidus	Disease	D003919
1141447	79	86	lithium	Chemical	D008094
1141447	95	113	diabetes insipidus	Disease	D003919
1141447	292	299	lithium	Chemical	D008094
1141447	CID	D008094	D003919

188339|t|Etiologic factors in the pathogenesis of liver tumors associated with oral contraceptives.
188339|a|Within the last several years, previously rare liver tumors have been seen in young women using oral contraceptive steroids. The Registry for Liver Tumors Associated with Oral Contraceptives at the University of California, Irvine, has clearly identified 27 cases. The recent literature contains 44 case reports. Common to these 71 cases has been a histopathologic diagnosis of focal nodular hyperplasia, adenoma, hamartoma, and hepatoma. Significant statistical etiologic factors include prolonged uninterrupted usage of oral contraceptive steroids. Eight deaths and liver rupture in 18 patients attest to the seriousness of this new potentially lethal adverse phenomenon.
188339	41	53	liver tumors	Disease	D008113
188339	70	89	oral contraceptives	Chemical	D003276
188339	138	150	liver tumors	Disease	D008113
188339	187	205	oral contraceptive	Chemical	D003276
188339	206	214	steroids	Chemical	D013256
188339	233	245	Liver Tumors	Disease	D008113
188339	262	281	Oral Contraceptives	Chemical	D003276
188339	469	494	focal nodular hyperplasia	Disease	D020518
188339	496	503	adenoma	Disease	D000236
188339	505	514	hamartoma	Disease	D006222
188339	520	528	hepatoma	Disease	D006528
188339	613	631	oral contraceptive	Chemical	D003276
188339	632	640	steroids	Chemical	D013256
188339	665	672	rupture	Disease	D012421
188339	CID	D003276	D008113

19135948|t|Graft-versus-host disease prophylaxis with everolimus and tacrolimus is associated with a high incidence of sinusoidal obstruction syndrome and microangiopathy: results of the EVTAC trial.
19135948|a|A calcineurin inhibitor combined with methotrexate is the standard prophylaxis for graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Everolimus, a derivative of sirolimus, seems to mediate antileukemia effects. We report on a combination of everolimus and tacrolimus in 24 patients (median age, 62 years) with either myelodysplastic syndrome (MDS; n = 17) or acute myeloid leukemia (AML; n = 7) undergoing intensive conditioning followed by HSCT from related (n = 4) or unrelated (n = 20) donors. All patients engrafted, and only 1 patient experienced grade IV mucositis. Nine patients (37%) developed acute grade II-IV GVHD, and 11 of 17 evaluable patients (64%) developed chronic extensive GVHD. Transplantation-associated microangiopathy (TMA) occurred in 7 patients (29%), with 2 cases of acute renal failure. The study was terminated prematurely because an additional 6 patients (25%) developed sinusoidal obstruction syndrome (SOS), which was fatal in 2 cases. With a median follow-up of 26 months, the 2-year overall survival rate was 47%. Although this new combination appears to be effective as a prophylactic regimen for acute GVHD, the incidence of TMA and SOS is considerably higher than seen with other regimens.
19135948	0	25	Graft-versus-host disease	Disease	D006086
19135948	43	53	everolimus	Chemical	C107135
19135948	58	68	tacrolimus	Chemical	D016559
19135948	108	139	sinusoidal obstruction syndrome	Disease	D006504
19135948	144	159	microangiopathy	Disease	D014652
19135948	227	239	methotrexate	Chemical	D008727
19135948	272	297	graft-versus-host disease	Disease	D006086
19135948	299	303	GVHD	Disease	D006086
19135948	370	380	Everolimus	Chemical	C107135
19135948	398	407	sirolimus	Chemical	D020123
19135948	478	488	everolimus	Chemical	C107135
19135948	493	503	tacrolimus	Chemical	D016559
19135948	554	578	myelodysplastic syndrome	Disease	D009190
19135948	580	583	MDS	Disease	D009190
19135948	596	618	acute myeloid leukemia	Disease	D015470
19135948	620	623	AML	Disease	D015470
19135948	798	807	mucositis	Disease	D052016
19135948	857	861	GVHD	Disease	D006086
19135948	929	933	GVHD	Disease	D006086
19135948	935	977	Transplantation-associated microangiopathy	Disease	D014652
19135948	979	982	TMA	Disease	D014652
19135948	1030	1049	acute renal failure	Disease	D058186
19135948	1137	1168	sinusoidal obstruction syndrome	Disease	D006504
19135948	1170	1173	SOS	Disease	D006504
19135948	1374	1378	GVHD	Disease	D006086
19135948	1397	1400	TMA	Disease	D014652
19135948	1405	1408	SOS	Disease	D006504
19135948	CID	D016559	D006504
19135948	CID	D016559	D014652
19135948	CID	C107135	D006504
19135948	CID	C107135	D058186
19135948	CID	D016559	D058186
19135948	CID	C107135	D014652

14704468|t|Effect of some convulsants on the protective activity of loreclezole and its combinations with valproate or clonazepam in amygdala-kindled rats.
14704468|a|Loreclezole (5 mg/kg) exerted a significant protective action in amygdala-kindled rats, reducing both seizure and afterdischarge durations. The combinations of loreclezole (2.5 mg/kg) with valproate, clonazepam, or carbamazepine (applied at their subprotective doses) also exhibited antiseizure effect in this test. However, only two first combinations occurred to be of pharmacodynamic nature. Among several chemoconvulsants, bicuculline, N-methyl-D-aspartic acid and BAY k-8644 (the opener of L-type calcium channels) reversed the protective activity of loreclezole alone and its combination with valproate. On the other hand, bicuculline, aminophylline and BAY k-8644 inhibited the anticonvulsive action of loreclezole combined with clonazepam. The results support the hypothesis that the protective activity of loreclezole and its combinations with other antiepileptics may involve potentiation of GABAergic neurotransmission and blockade of L-type of calcium channels.
14704468	57	68	loreclezole	Chemical	C066440
14704468	95	104	valproate	Chemical	D014635
14704468	108	118	clonazepam	Chemical	D002998
14704468	145	156	Loreclezole	Chemical	C066440
14704468	247	254	seizure	Disease	D012640
14704468	305	316	loreclezole	Chemical	C066440
14704468	334	343	valproate	Chemical	D014635
14704468	345	355	clonazepam	Chemical	D002998
14704468	360	373	carbamazepine	Chemical	D002220
14704468	572	583	bicuculline	Chemical	D001640
14704468	585	609	N-methyl-D-aspartic acid	Chemical	D016202
14704468	614	624	BAY k-8644	Chemical	D001498
14704468	647	654	calcium	Chemical	D002118
14704468	701	712	loreclezole	Chemical	C066440
14704468	744	753	valproate	Chemical	D014635
14704468	774	785	bicuculline	Chemical	D001640
14704468	787	800	aminophylline	Chemical	D000628
14704468	805	815	BAY k-8644	Chemical	D001498
14704468	855	866	loreclezole	Chemical	C066440
14704468	881	891	clonazepam	Chemical	D002998
14704468	960	971	loreclezole	Chemical	C066440
14704468	1101	1108	calcium	Chemical	D002118
14704468	CID	D001640	D012640
14704468	CID	D000628	D012640
14704468	CID	D001498	D012640

12549952|t|Acute liver failure with concurrent bupropion and carbimazole therapy.
12549952|a|OBJECTIVE: To report a case of fatal liver failure possibly associated with concurrent use of bupropion and carbimazole. CASE SUMMARY: A 41-year-old Chinese man with a history of hyperthyroidism had been treated with carbimazole and propranolol for the past 5 years. He received a 10-day course of bupropion as an aid for smoking cessation 10 weeks prior to presentation. He developed acute liver failure with rapid deterioration of renal function. Liver biopsy showed evidence of nonspecific drug-induced acute liver injury. His condition was further complicated by sepsis and coagulopathy. Death resulted 19 days after the onset of symptoms. The likelihood that bupropion induced hepatotoxicity in our patient was possible, based on the Naranjo probability scale. DISCUSSION: Although there is increasing evidence of hepatotoxicity induced by bupropion, this is the first case of fatality that could have resulted from acute liver failure in a patient receiving bupropion while on concomitant treatment with carbimazole. CONCLUSIONS: Clinicians should be aware of the possibility of acute liver insult induced by bupropion given concurrently with other hepatotoxic drugs.
12549952	0	19	Acute liver failure	Disease	D017114
12549952	36	45	bupropion	Chemical	D016642
12549952	50	61	carbimazole	Chemical	D002231
12549952	108	121	liver failure	Disease	D017093
12549952	165	174	bupropion	Chemical	D016642
12549952	179	190	carbimazole	Chemical	D002231
12549952	250	265	hyperthyroidism	Disease	D006980
12549952	288	299	carbimazole	Chemical	D002231
12549952	304	315	propranolol	Chemical	D011433
12549952	369	378	bupropion	Chemical	D016642
12549952	456	475	acute liver failure	Disease	D017114
12549952	564	595	drug-induced acute liver injury	Disease	D056486
12549952	638	644	sepsis	Disease	D018805
12549952	649	661	coagulopathy	Disease	D001778
12549952	735	744	bupropion	Chemical	D016642
12549952	753	767	hepatotoxicity	Disease	D056486
12549952	890	904	hepatotoxicity	Disease	D056486
12549952	916	925	bupropion	Chemical	D016642
12549952	992	1011	acute liver failure	Disease	D017114
12549952	1035	1044	bupropion	Chemical	D016642
12549952	1081	1092	carbimazole	Chemical	D002231
12549952	1156	1174	acute liver insult	Disease	D017114
12549952	1186	1195	bupropion	Chemical	D016642
12549952	1226	1237	hepatotoxic	Disease	D056486
12549952	CID	D016642	D056486
12549952	CID	D002231	D056486
12549952	CID	D002231	D017114
12549952	CID	D016642	D017114

19370593|t|Long term hormone therapy for perimenopausal and postmenopausal women.
19370593|a|BACKGROUND: Hormone therapy (HT) is widely used for controlling menopausal symptoms and has also been used for the management and prevention of cardiovascular disease, osteoporosis and dementia in older women. This is an updated version of the original Cochrane review first published in 2005. OBJECTIVES: To assess the effect of long-term HT on mortality, cardiovascular outcomes, cancer, gallbladder disease, cognition, fractures and quality of life. SEARCH STRATEGY: We searched the following databases to November 2007: Trials Register of the Cochrane Menstrual Disorders and Subfertility Group, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Biological Abstracts. Also relevant non-indexed journals and conference abstracts. SELECTION CRITERIA: Randomised double-blind trials of HT versus placebo, taken for at least one year by perimenopausal or postmenopausal women. HT included oestrogens, with or without progestogens, via oral, transdermal, subcutaneous or transnasal routes. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. MAIN RESULTS: Nineteen trials involving 41,904 women were included. In relatively healthy women, combined continuous HT significantly increased the risk of venous thrombo-embolism or coronary event (after one year's use), stroke (after three years), breast cancer and gallbladder disease. Long-term oestrogen-only HT significantly increased the risk of venous thrombo-embolism, stroke and gallbladder disease (after one to two years, three years and seven years' use respectively), but did not significantly increase the risk of breast cancer. The only statistically significant benefits of HT were a decreased incidence of fractures and (for combined HT) colon cancer, with long-term use. Among women aged over 65 who were relatively healthy (i.e. generally fit, without overt disease) and taking continuous combined HT, there was a statistically significant increase in the incidence of dementia. Among women with cardiovascular disease, long-term use of combined continuous HT significantly increased the risk of venous thrombo-embolism.One trial analysed subgroups of 2839 relatively healthy 50 to 59 year old women taking combined continuous HT and 1637 taking oestrogen-only HT, versus similar-sized placebo groups. The only significantly increased risk reported was for venous thrombo-embolism in women taking combined continuous HT: their absolute risk remained low, at less than 1/500. However, this study was not powered to detect differences between groups of younger women. AUTHORS' CONCLUSIONS: HT is not indicated for the routine management of chronic disease. We need more evidence on the safety of HT for menopausal symptom control, though short-term use appears to be relatively safe for healthy younger women.
19370593	215	237	cardiovascular disease	Disease	D002318
19370593	239	251	osteoporosis	Disease	D010024
19370593	256	264	dementia	Disease	D003704
19370593	453	459	cancer	Disease	D009369
19370593	461	480	gallbladder disease	Disease	D005705
19370593	493	502	fractures	Disease	D050723
19370593	627	646	Menstrual Disorders	Disease	D008599
19370593	975	985	oestrogens	Chemical	D004967
19370593	1003	1015	progestogens	Chemical	D011374
19370593	1330	1353	venous thrombo-embolism	Disease	D054556
19370593	1396	1402	stroke	Disease	D020521
19370593	1424	1437	breast cancer	Disease	D001943
19370593	1442	1461	gallbladder disease	Disease	D005705
19370593	1473	1482	oestrogen	Chemical	D004967
19370593	1527	1550	venous thrombo-embolism	Disease	D054556
19370593	1552	1558	stroke	Disease	D020521
19370593	1563	1582	gallbladder disease	Disease	D005705
19370593	1703	1716	breast cancer	Disease	D001943
19370593	1798	1807	fractures	Disease	D050723
19370593	1830	1842	colon cancer	Disease	D003110
19370593	2063	2071	dementia	Disease	D003704
19370593	2090	2112	cardiovascular disease	Disease	D002318
19370593	2190	2213	venous thrombo-embolism	Disease	D054556
19370593	2340	2349	oestrogen	Chemical	D004967
19370593	2451	2474	venous thrombo-embolism	Disease	D054556
19370593	CID	D011374	D054556
19370593	CID	D004967	D005705
19370593	CID	D004967	D020521
19370593	CID	D004967	D054556
19370593	CID	D004967	D003704
19370593	CID	D011374	D003704

17019386|t|Passage of mannitol into the brain around gliomas: a potential cause of rebound phenomenon. A study on 21 patients.
17019386|a|AIM: Widespread use of mannitol to reduce brain edema and lower elevated ICP in brain tumor patients continues to be afflicted by the so-called rebound phenomenon. Leakage of mannitol into the brain parenchyma through an altered BBB and secondary reversal of osmotic gradient is considered the major cause of rebound . This has only been demonstrated experimentally in animals. As a contribution to this issue we decided to research the possible passage of mannitol into the brain after administration to 21 brain tumor patients. METHODS: Mannitol (18% solution; 1 g/kg) was administered as a bolus to patients (ten had malignant glioma, seven brain metastases and four meningioma) about 30 minutes before craniotomy. During resection, a sample of the surrounding edematous white matter was taken at the same time as a 10 ml venous blood sample. Mannitol concentrations were measured in plasma and white matter by a modified version of the enzyme assay of Blonquist et al. RESULTS: In most glioma patients, mannitol concentrations in white matter were 2 to 6 times higher than in plasma (mean 3.5 times). In meningioma and metastases patients plasma concentrations of mannitol were higher than white matter concentrations except in three cases with infiltration by neoplastic cells. CONCLUSIONS: The results of our study show that even after a single bolus, mannitol may leak through the altered BBB near gliomas, reversing the initial plasma-to-blood osmotic gradient, aggravating peritumoral edema and promoting rebound of ICP.
17019386	11	19	mannitol	Chemical	D008353
17019386	42	49	gliomas	Disease	D005910
17019386	139	147	mannitol	Chemical	D008353
17019386	158	169	brain edema	Disease	D001929
17019386	180	192	elevated ICP	Disease	D019586
17019386	196	207	brain tumor	Disease	D001932
17019386	291	299	mannitol	Chemical	D008353
17019386	573	581	mannitol	Chemical	D008353
17019386	624	635	brain tumor	Disease	D001932
17019386	655	663	Mannitol	Chemical	D008353
17019386	736	752	malignant glioma	Disease	D005910
17019386	766	776	metastases	Disease	D009362
17019386	786	796	meningioma	Disease	D008579
17019386	880	889	edematous	Disease	D004487
17019386	962	970	Mannitol	Chemical	D008353
17019386	1106	1112	glioma	Disease	D005910
17019386	1123	1131	mannitol	Chemical	D008353
17019386	1224	1234	meningioma	Disease	D008579
17019386	1239	1249	metastases	Disease	D009362
17019386	1284	1292	mannitol	Chemical	D008353
17019386	1474	1482	mannitol	Chemical	D008353
17019386	1521	1528	gliomas	Disease	D005910
17019386	1610	1615	edema	Disease	D004487
17019386	CID	D008353	D019586

12452237|t|Can lidocaine reduce succinylcholine induced postoperative myalgia?
12452237|a|This study was undertaken to determine the effect of lidocaine pretreatment on reduction of succinylcholine-induced myalgia in patients undergoing general anesthesia for gynecological surgery. One hundred and thirty-five patients were assigned to one of three groups in a prospective, double blind, randomized manner. Group PS, the control group, received normal saline and succinylcholine 1.5 mg x kg(-1); Group LS, lidocaine 1.5 mg x kg(-1) and succinylcholine 1.5 mg x kg(-1); Group PR, normal saline and rocuronium 0.6 mg x kg(-1). Morphine 0.1 mg x kg(-1) iv was given for premedication and all patients were monitored with a noninvasive blood pressure monitor, ECG and pulse oximetry. Anesthesia was induced with 5 mg.kg(-1) thiopental iv. followed by succinylcholine (Group PS, LS) or rocuronium (Group PR) for tracheal intubation. Following administration of these agents, the presence, and degree of fasciculation were assessed visually on a four point scale by one investigator who was blinded to the drug administered. The blood pressure and heart rate of each patient were monitored on nine occasions. Twenty-four hours later, any myalgia experienced was assessed according to a structured questionaire and graded by a four point scale by one investigator blinded to the intraoperative management. The results indicate that muscle fasciculation was not found in Group PR while the patients in Group LS had a lower incidence of muscle fasciculation than those in Group PS (p < 0.001). At 24 h, the incidence of myalgia was higher in Group PS than in Group LS and PR (p < 0.05). A correlation was not found between the incidence of myalgia and the occurrence of muscle fasciculation. The changes in systolic and diastolic blood pressure and heart rate were not significant among the three groups. In conclusion, where succinylcholine is used, lidocaine is proven to be the useful pretreatment agent for the reduction of postoperative myalgia.
12452237	4	13	lidocaine	Chemical	D008012
12452237	21	36	succinylcholine	Chemical	D013390
12452237	45	66	postoperative myalgia	Disease	D010149
12452237	121	130	lidocaine	Chemical	D008012
12452237	160	175	succinylcholine	Chemical	D013390
12452237	184	191	myalgia	Disease	D063806
12452237	442	457	succinylcholine	Chemical	D013390
12452237	485	494	lidocaine	Chemical	D008012
12452237	515	530	succinylcholine	Chemical	D013390
12452237	576	586	rocuronium	Chemical	C061870
12452237	604	612	Morphine	Chemical	D009020
12452237	799	809	thiopental	Chemical	D013874
12452237	826	841	succinylcholine	Chemical	D013390
12452237	860	870	rocuronium	Chemical	C061870
12452237	977	990	fasciculation	Disease	D005207
12452237	1211	1218	myalgia	Disease	D063806
12452237	1404	1424	muscle fasciculation	Disease	D005207
12452237	1507	1527	muscle fasciculation	Disease	D005207
12452237	1590	1597	myalgia	Disease	D063806
12452237	1710	1717	myalgia	Disease	D063806
12452237	1740	1760	muscle fasciculation	Disease	D005207
12452237	1896	1911	succinylcholine	Chemical	D013390
12452237	1921	1930	lidocaine	Chemical	D008012
12452237	1998	2019	postoperative myalgia	Disease	D010149
12452237	CID	D013390	D005207
12452237	CID	D013390	D010149

9564988|t|Open-label assessment of levofloxacin for the treatment of acute bacterial sinusitis in adults.
9564988|a|PURPOSE: To evaluate the efficacy and safety of levofloxacin (500 mg orally once daily for 10 to 14 days) in treating adult outpatients with acute bacterial sinusitis. PATIENTS AND METHODS: A total of 329 patients enrolled in the study at 24 centers. All patients had a pre-therapy Gram's stain and culture of sinus exudate obtained by antral puncture or nasal endoscopy. Clinical response was assessed on the basis of signs and symptoms and sinus radiograph or computed tomography results. Microbiologic cure rates were determined on the basis of presumed plus documented eradication of the pre-therapy pathogen(s). RESULTS: The most common pathogens were Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus, and Moraxella catarrhalis. Of 300 clinically evaluable patients, 175 (58%) were cured and 90 (30%) were improved at the post-therapy evaluation, resulting in a clinical success rate of 88%. Thirty-five patients (12%) clinically failed treatment. The microbiologic eradication rate (presumed plus documented) among 138 microbiologically evaluable patients was 92%. Microbiologic eradication rates (presumed plus documented) of the most common pathogens ranged from 93% (M. catarrhalis) to 100% (S. pneumoniae) at the post-therapy visit. All but one of the 265 patients who were cured or improved at post-therapy returned for a long-term follow-up visit; 243 (92%) remained well 4 to 6 weeks after therapy; and 21 (8%) had a relapse of symptoms. Adverse events considered to be related to levofloxacin administration were reported by 29 patients (9%). The most common drug-related adverse events were diarrhea, flatulence, and nausea; most adverse events were mild to moderate in severity. CONCLUSION: The results of this study indicate that levofloxacin 500 mg once daily is an effective and safe treatment for acute bacterial sinusitis.
9564988	25	37	levofloxacin	Chemical	D064704
9564988	75	84	sinusitis	Disease	D012852
9564988	144	156	levofloxacin	Chemical	D064704
9564988	253	262	sinusitis	Disease	D012852
9564988	1613	1625	levofloxacin	Chemical	D064704
9564988	1725	1733	diarrhea	Disease	D003967
9564988	1735	1745	flatulence	Disease	D005414
9564988	1751	1757	nausea	Disease	D009325
9564988	1866	1878	levofloxacin	Chemical	D064704
9564988	1952	1961	sinusitis	Disease	D012852
9564988	CID	D064704	D005414
9564988	CID	D064704	D003967
9564988	CID	D064704	D009325

7596955|t|Clinical evaluation on combined administration of oral prostacyclin analogue beraprost and phosphodiesterase inhibitor cilostazol.
7596955|a|Among various oral antiplatelets, a combination of a novel prostacyclin analogue beraprost (BPT) and a potent phosphodiesterase inhibitor cilostazol (CLZ) may result in untoward clinical effects due to possible synergistic elevation of intracellular cAMP (cyclic adenosine 3',5'-monophosphate). Thereby, a clinical study of the combined administration of the two agents was attempted. Twelve healthy volunteers were assigned to take BPT/CLZ in the following schedule; BPT: 40 micrograms at day 1 and 120 micrograms t.i.d. from day 7 to 14, CLZ: 200 mg t.i.d. from day 3 to 14. At various time intervals, physical examination and blood collection for ex vivo platelet aggregation and determination of intraplatelet cAMP were performed. Throughout the observation period, no significant alteration in vital signs was observed. Seven out of 12 subjects experienced headache of a short duration accompanying facial flush in one and nausea in one, especially after ingestion of CLZ. All of these symptoms, probably caused by the vasodilating effect of the two agents, were of mild degree and no special treatment was required. Intraplatelet cAMP content was gradually but significantly increased to 9.84 +/- 4.59 pmol per 10(9) platelets at day 14 in comparison with the initial value (6.87 +/- 2.25 pmol). The platelet aggregability was significantly suppressed at various time intervals but no additive or synergistic inhibitory effect by the combined administration was noted. In conclusion, the combined administration of BPT/CLZ is safe at doses used in the study, though the beneficial clinical effect of the combined administration has yet to be elucidated.
7596955	55	67	prostacyclin	Chemical	D011464
7596955	77	86	beraprost	Chemical	C048081
7596955	119	129	cilostazol	Chemical	C045645
7596955	190	202	prostacyclin	Chemical	D011464
7596955	212	221	beraprost	Chemical	C048081
7596955	223	226	BPT	Chemical	C048081
7596955	269	279	cilostazol	Chemical	C045645
7596955	281	284	CLZ	Chemical	C045645
7596955	381	385	cAMP	Chemical	D000242
7596955	387	423	cyclic adenosine 3',5'-monophosphate	Chemical	D000242
7596955	564	567	BPT	Chemical	C048081
7596955	568	571	CLZ	Chemical	C045645
7596955	599	602	BPT	Chemical	C048081
7596955	671	674	CLZ	Chemical	C045645
7596955	789	809	platelet aggregation	Disease	D001791
7596955	845	849	cAMP	Chemical	D000242
7596955	993	1001	headache	Disease	D006261
7596955	1035	1047	facial flush	Disease	D005483
7596955	1059	1065	nausea	Disease	D009325
7596955	1104	1107	CLZ	Chemical	C045645
7596955	1267	1271	cAMP	Chemical	D000242
7596955	1652	1655	BPT	Chemical	C048081
7596955	1656	1659	CLZ	Chemical	C045645
7596955	CID	C045645	D005483
7596955	CID	C045645	D009325
7596955	CID	C048081	D006261
7596955	CID	C048081	D005483
7596955	CID	C045645	D006261
7596955	CID	C048081	D009325

17965424|t|Gastrointestinal tolerability of etoricoxib in rheumatoid arthritis patients: results of the etoricoxib vs diclofenac sodium gastrointestinal tolerability and effectiveness trial (EDGE-II).
17965424|a|OBJECTIVE: A randomised, double-blind study to compare the gastrointestinal (GI) tolerability, safety and efficacy of etoricoxib and diclofenac in patients with rheumatoid arthritis (RA). PATIENTS AND METHODS: A total of 4086 patients (mean age 60.8 years) diagnosed with RA were enrolled and received etoricoxib 90 mg daily (n = 2032) or diclofenac 75 mg twice daily (n = 2054). Use of gastroprotective agents and low-dose aspirin was allowed. The prespecified primary end point consisted of the cumulative rate of patient discontinuations due to clinical and laboratory GI adverse experiences (AEs). General safety was also assessed, including adjudicated thrombotic cardiovascular event data. Efficacy was evaluated using the Patient Global Assessment of Disease Status (PGADS; 0-4 point scale). RESULTS: Mean (SD; maximum) duration of treatment was 19.3 (10.3; 32.9) and 19.1 (10.4; 33.1) months in the etoricoxib and diclofenac groups, respectively. The cumulative discontinuation rate due to GI AEs was significantly lower with etoricoxib than diclofenac (5.2 vs 8.5 events per 100 patient-years, respectively; hazard ratio 0.62 (95% CI: 0.47, 0.81; p<or=0.001)). The incidence of discontinuations for hypertension-related and oedema-related AEs were significantly higher with etoricoxib (2.5% and 1.1% respectively) compared with diclofenac (1.5% and 0.4% respectively; p<0.001 for hypertension and p<0.01 for oedema). Etoricoxib and diclofenac treatment resulted in similar efficacy (PGADS mean changes from baseline -0.62 vs -0.58, respectively). CONCLUSIONS: Etoricoxib 90 mg demonstrated a significantly lower risk for discontinuing treatment due to GI AEs compared with diclofenac 150 mg. Discontinuations from renovascular AEs, although less common than discontinuations from GI AEs, were significantly higher with etoricoxib.
17965424	33	43	etoricoxib	Chemical	C422649
17965424	47	67	rheumatoid arthritis	Disease	D001172
17965424	93	103	etoricoxib	Chemical	C422649
17965424	107	124	diclofenac sodium	Chemical	D004008
17965424	308	318	etoricoxib	Chemical	C422649
17965424	323	333	diclofenac	Chemical	D004008
17965424	351	371	rheumatoid arthritis	Disease	D001172
17965424	373	375	RA	Disease	D001172
17965424	462	464	RA	Disease	D001172
17965424	492	502	etoricoxib	Chemical	C422649
17965424	529	539	diclofenac	Chemical	D004008
17965424	614	621	aspirin	Chemical	D001241
17965424	848	873	thrombotic cardiovascular	Disease	D002318
17965424	1097	1107	etoricoxib	Chemical	C422649
17965424	1112	1122	diclofenac	Chemical	D004008
17965424	1188	1194	GI AEs	Disease	D005767
17965424	1224	1234	etoricoxib	Chemical	C422649
17965424	1240	1250	diclofenac	Chemical	D004008
17965424	1398	1410	hypertension	Disease	D006973
17965424	1423	1429	oedema	Disease	D004487
17965424	1473	1483	etoricoxib	Chemical	C422649
17965424	1527	1537	diclofenac	Chemical	D004008
17965424	1579	1591	hypertension	Disease	D006973
17965424	1607	1613	oedema	Disease	D004487
17965424	1616	1626	Etoricoxib	Chemical	C422649
17965424	1631	1641	diclofenac	Chemical	D004008
17965424	1759	1769	Etoricoxib	Chemical	C422649
17965424	1851	1857	GI AEs	Disease	D005767
17965424	1872	1882	diclofenac	Chemical	D004008
17965424	1979	1985	GI AEs	Disease	D005767
17965424	2018	2028	etoricoxib	Chemical	C422649
17965424	CID	C422649	D004487
17965424	CID	D004008	D005767
17965424	CID	C422649	D006973

17042884|t|Placebo-level incidence of extrapyramidal symptoms (EPS) with quetiapine in controlled studies of patients with bipolar mania.
17042884|a|OBJECTIVES: To evaluate extrapyramidal symptoms (EPS), including akathisia, with quetiapine in patients with bipolar mania. METHODS: Data were analyzed from four similarly designed, randomized, double-blind, 3- to 12-week studies. Two studies evaluated quetiapine monotherapy (up to 800 mg/day) (n = 209) versus placebo (n = 198), with lithium or haloperidol monotherapy as respective active controls. Two studies evaluated quetiapine (up to 800 mg/day) in combination with a mood stabilizer (lithium or divalproex, QTP + Li/DVP) (n = 196) compared to placebo and mood stabilizer (PBO + Li/DVP) (n = 203). Extrapyramidal symptoms were evaluated using the Simpson-Angus Scale (SAS), the Barnes Akathisia Rating Scale (BARS), adverse event reports and anticholinergic drug usage. RESULTS: The incidence of EPS-related adverse events, including akathisia, was no different with quetiapine monotherapy (12.9%) than with placebo (13.1%). Similarly, EPS-related adverse events with QTP + Li/DVP (21.4%) were no different than with PBO + Li/DVP (19.2%). Adverse events related to EPS occurred in 59.6% of patients treated with haloperidol (n = 99) monotherapy, whereas 26.5% of patients treated with lithium (n = 98) monotherapy experienced adverse events related to EPS. The incidence of akathisia was low and similar with quetiapine monotherapy (3.3%) and placebo (6.1%), and with QTP + Li/DVP (3.6%) and PBO + Li/DVP (4.9%). Lithium was associated with a significantly higher incidence (p < 0.05) of tremor (18.4%) than quetiapine (5.6%); cerebellar tremor, which is a known adverse effect of lithium, may have contributed to the elevated rate of tremor in patients receiving lithium therapy. Haloperidol induced a significantly higher incidence (p < 0.001) of akathisia (33.3% versus 5.9%), tremor (30.3% versus 7.8%), and extrapyramidal syndrome (35.4% versus 5.9%) than quetiapine. No significant differences were observed between quetiapine and placebo on SAS and BARS scores. Anticholinergic use was low and similar with quetiapine or placebo. CONCLUSIONS: In bipolar mania, the incidence of EPS, including akathisia, with quetiapine therapy is similar to that with placebo.
17042884	27	50	extrapyramidal symptoms	Disease	D001480
17042884	52	55	EPS	Disease	D001480
17042884	62	72	quetiapine	Chemical	C069541
17042884	112	125	bipolar mania	Disease	D001714
17042884	151	174	extrapyramidal symptoms	Disease	D001480
17042884	176	179	EPS	Disease	D001480
17042884	192	201	akathisia	Disease	D017109
17042884	208	218	quetiapine	Chemical	C069541
17042884	236	249	bipolar mania	Disease	D001714
17042884	380	390	quetiapine	Chemical	C069541
17042884	463	470	lithium	Chemical	D008094
17042884	474	485	haloperidol	Chemical	D006220
17042884	551	561	quetiapine	Chemical	C069541
17042884	620	627	lithium	Chemical	D008094
17042884	631	641	divalproex	Chemical	D014635
17042884	643	646	QTP	Chemical	C069541
17042884	649	651	Li	Chemical	D008094
17042884	652	655	DVP	Chemical	D014635
17042884	714	716	Li	Chemical	D008094
17042884	717	720	DVP	Chemical	D014635
17042884	733	756	Extrapyramidal symptoms	Disease	D001480
17042884	931	934	EPS	Disease	D001480
17042884	969	978	akathisia	Disease	D017109
17042884	1002	1012	quetiapine	Chemical	C069541
17042884	1071	1074	EPS	Disease	D001480
17042884	1103	1106	QTP	Chemical	C069541
17042884	1109	1111	Li	Chemical	D008094
17042884	1112	1115	DVP	Chemical	D014635
17042884	1158	1160	Li	Chemical	D008094
17042884	1161	1164	DVP	Chemical	D014635
17042884	1200	1203	EPS	Disease	D001480
17042884	1247	1258	haloperidol	Chemical	D006220
17042884	1320	1327	lithium	Chemical	D008094
17042884	1387	1390	EPS	Disease	D001480
17042884	1409	1418	akathisia	Disease	D017109
17042884	1444	1454	quetiapine	Chemical	C069541
17042884	1503	1506	QTP	Chemical	C069541
17042884	1509	1511	Li	Chemical	D008094
17042884	1512	1515	DVP	Chemical	D014635
17042884	1533	1535	Li	Chemical	D008094
17042884	1536	1539	DVP	Chemical	D014635
17042884	1548	1555	Lithium	Chemical	D008094
17042884	1623	1629	tremor	Disease	D014202
17042884	1643	1653	quetiapine	Chemical	C069541
17042884	1673	1679	tremor	Disease	D014202
17042884	1716	1723	lithium	Chemical	D008094
17042884	1770	1776	tremor	Disease	D014202
17042884	1799	1806	lithium	Chemical	D008094
17042884	1816	1827	Haloperidol	Chemical	D006220
17042884	1884	1893	akathisia	Disease	D017109
17042884	1915	1921	tremor	Disease	D014202
17042884	1947	1970	extrapyramidal syndrome	Disease	D001480
17042884	1996	2006	quetiapine	Chemical	C069541
17042884	2057	2067	quetiapine	Chemical	C069541
17042884	2149	2159	quetiapine	Chemical	C069541
17042884	2188	2201	bipolar mania	Disease	D001714
17042884	2220	2223	EPS	Disease	D001480
17042884	2235	2244	akathisia	Disease	D017109
17042884	2251	2261	quetiapine	Chemical	C069541
17042884	CID	D006220	D001480
17042884	CID	D006220	D014202
17042884	CID	D008094	D001480
17042884	CID	D008094	D014202
17042884	CID	D006220	D017109

8586822|t|Contribution of the sympathetic nervous system to salt-sensitivity in lifetime captopril-treated spontaneously hypertensive rats.
8586822|a|OBJECTIVE: To test the hypothesis that, in lifetime captopril-treated spontaneously hypertensive rats (SHR), the sympathetic nervous system contributes importantly to the hypertensive effect of dietary sodium chloride supplementation. METHODS: Male SHR (aged 6 weeks) that had been treated from conception onward with either captopril or vehicle remained on a basal sodium chloride diet or were fed a high sodium chloride diet. After 2 weeks, the rats were subjected to ganglionic blockade and 2 days later, an infusion of clonidine. RESULTS: Lifetime captopril treatment significantly lowered mean arterial pressure in both groups. Intravenous infusion of the ganglionic blocker hexamethonium resulted in a rapid decline in MAP that eliminated the dietary sodium chloride-induced increase in MAP in both groups. Infusion of the central nervous system alpha2-adrenergic receptor agonist clonidine also resulted in a greater reduction in MAP in both groups of SHR that were fed the high (compared with the basal) sodium chloride diet. CONCLUSIONS: In both lifetime captopril-treated and control SHR, the sympathetic nervous system contributes to the pressor effects of a high sodium chloride diet.
8586822	79	88	captopril	Chemical	D002216
8586822	111	123	hypertensive	Disease	D006973
8586822	182	191	captopril	Chemical	D002216
8586822	214	226	hypertensive	Disease	D006973
8586822	301	313	hypertensive	Disease	D006973
8586822	324	347	dietary sodium chloride	Chemical	D017673
8586822	455	464	captopril	Chemical	D002216
8586822	496	511	sodium chloride	Chemical	D012965
8586822	536	551	sodium chloride	Chemical	D012965
8586822	653	662	clonidine	Chemical	D003000
8586822	682	691	captopril	Chemical	D002216
8586822	810	823	hexamethonium	Chemical	D018738
8586822	879	902	dietary sodium chloride	Chemical	D017673
8586822	911	926	increase in MAP	Disease	D006973
8586822	982	1016	alpha2-adrenergic receptor agonist	Chemical	D058647
8586822	1017	1026	clonidine	Chemical	D003000
8586822	1142	1157	sodium chloride	Chemical	D012965
8586822	1194	1203	captopril	Chemical	D002216
8586822	1305	1320	sodium chloride	Chemical	D012965
8586822	CID	D017673	D006973

3961813|t|Dose-related beneficial and adverse effects of dietary corticosterone on organophosphorus-induced delayed neuropathy in chickens.
3961813|a|Tri-ortho-tolyl phosphate (TOTP), 360 mg/kg, po, and 0,0'-diisopropyl phosphorofluoridate (DFP), 1 mg/kg sc, were administered to adult White Leghorn chickens 24 hr after they were placed on diets containing 0 to 300 ppm corticosterone. Supplemented diets were continued until clinical signs and lesions of delayed neuropathy appeared. Although low concentrations (less than or equal to 50 ppm) of corticosterone had beneficial effects on TOTP-induced neuropathy, greater than or equal to 200 ppm exacerbated clinical signs in chickens given either TOTP or DFP. Neurotoxic esterase activities 24 hr after TOTP or DFP were less than 20% of values measured in chickens not given organophosphorous compounds. Chickens given 200 ppm corticosterone without TOTP or DFP had significantly elevated activity of plasma cholinesterase and significantly inhibited activity of liver carboxylesterase. Degenerating myelinated fibers were also evident in distal levels of the peripheral nerves of chickens given TOTP or DFP.
3961813	55	69	corticosterone	Chemical	D003345
3961813	73	89	organophosphorus	Chemical	D010755
3961813	106	116	neuropathy	Disease	D009422
3961813	130	155	Tri-ortho-tolyl phosphate	Chemical	C025541
3961813	157	161	TOTP	Chemical	C025541
3961813	183	219	0,0'-diisopropyl phosphorofluoridate	Chemical	D007531
3961813	221	224	DFP	Chemical	D007531
3961813	351	365	corticosterone	Chemical	D003345
3961813	445	455	neuropathy	Disease	D009422
3961813	528	542	corticosterone	Chemical	D003345
3961813	569	573	TOTP	Chemical	C025541
3961813	582	592	neuropathy	Disease	D009422
3961813	679	683	TOTP	Chemical	C025541
3961813	687	690	DFP	Chemical	D007531
3961813	692	702	Neurotoxic	Disease	D020258
3961813	735	739	TOTP	Chemical	C025541
3961813	743	746	DFP	Chemical	D007531
3961813	807	824	organophosphorous	Chemical	D010755
3961813	859	873	corticosterone	Chemical	D003345
3961813	882	886	TOTP	Chemical	C025541
3961813	890	893	DFP	Chemical	D007531
3961813	1019	1049	Degenerating myelinated fibers	Disease	D009410
3961813	1128	1132	TOTP	Chemical	C025541
3961813	1136	1139	DFP	Chemical	D007531
3961813	CID	D007531	D009410
3961813	CID	D007531	D009422
3961813	CID	C025541	D009410
3961813	CID	C025541	D009422

20973483|t|In vivo characterization of a dual adenosine A2A/A1 receptor antagonist in animal models of Parkinson's disease.
20973483|a|The in vivo characterization of a dual adenosine A(2A)/A(1) receptor antagonist in several animal models of Parkinson's disease is described. Discovery and scale-up syntheses of compound 1 are described in detail, highlighting optimization steps that increased the overall yield of 1 from 10.0% to 30.5%. Compound 1 is a potent A(2A)/A(1) receptor antagonist in vitro (A(2A) K(i) = 4.1 nM; A(1) K(i) = 17.0 nM) that has excellent activity, after oral administration, across a number of animal models of Parkinson's disease including mouse and rat models of haloperidol-induced catalepsy, mouse model of reserpine-induced akinesia, rat 6-hydroxydopamine (6-OHDA) lesion model of drug-induced rotation, and MPTP-treated non-human primate model.
20973483	35	71	adenosine A2A/A1 receptor antagonist	Chemical	D058915
20973483	92	111	Parkinson's disease	Disease	D010300
20973483	152	192	adenosine A(2A)/A(1) receptor antagonist	Chemical	D058915
20973483	221	240	Parkinson's disease	Disease	D010300
20973483	616	635	Parkinson's disease	Disease	D010300
20973483	670	681	haloperidol	Chemical	D006220
20973483	690	699	catalepsy	Disease	D002375
20973483	716	725	reserpine	Chemical	D012110
20973483	734	742	akinesia	Disease	D004409
20973483	748	765	6-hydroxydopamine	Chemical	D016627
20973483	767	773	6-OHDA	Chemical	D016627
20973483	818	822	MPTP	Chemical	D015632
20973483	CID	D012110	D004409
20973483	CID	D006220	D002375

17511042|t|An extremely rare case of delusional parasitosis in a chronic hepatitis C patient during pegylated interferon alpha-2b and ribavirin treatment.
17511042|a|During treatment of chronic hepatitis C patients with interferon and ribavirin, a lot of side effects are described. Twenty-three percent to 44% of patients develop depression. A minority of patients evolve to psychosis. To the best of our knowledge, no cases of psychogenic parasitosis occurring during interferon therapy have been described in the literature. We present a 49-year-old woman who developed a delusional parasitosis during treatment with pegylated interferon alpha-2b weekly and ribavirin. She complained of seeing parasites and the larvae of fleas in her stools. This could not be confirmed by any technical examination. All the complaints disappeared after stopping pegylated interferon alpha-2b and reappeared after restarting it. She had a complete sustained viral response.
17511042	26	48	delusional parasitosis	Disease	D063726
17511042	54	73	chronic hepatitis C	Disease	D019698
17511042	89	118	pegylated interferon alpha-2b	Chemical	C417083
17511042	123	132	ribavirin	Chemical	D012254
17511042	164	183	chronic hepatitis C	Disease	D019698
17511042	213	222	ribavirin	Chemical	D012254
17511042	309	319	depression	Disease	D003866
17511042	354	363	psychosis	Disease	D011605
17511042	407	430	psychogenic parasitosis	Disease	D063726
17511042	553	575	delusional parasitosis	Disease	D063726
17511042	598	627	pegylated interferon alpha-2b	Chemical	C417083
17511042	639	648	ribavirin	Chemical	D012254
17511042	828	857	pegylated interferon alpha-2b	Chemical	C417083
17511042	CID	C417083	D063726
17511042	CID	D012254	D063726

16720068|t|Possible neuroleptic malignant syndrome related to concomitant treatment with paroxetine and alprazolam.
16720068|a|A 74-year-old man with depressive symptoms was admitted to a psychiatric hospital due to insomnia, loss of appetite, exhaustion, and agitation. Medical treatment was initiated at a daily dose of 20 mg paroxetine and 1.2 mg alprazolam. On the 10th day of paroxetine and alprazolam treatment, the patient exhibited marked psychomotor retardation, disorientation, and severe muscle rigidity with tremors. The patient had a fever (38.2 degrees C), fluctuating blood pressure (between 165/90 and 130/70 mg mm Hg), and severe extrapyramidal symptoms. Laboratory tests showed an elevation of creatine phosphokinase (2218 IU/L), aspartate aminotransferase (134 IU/L), alanine aminotransferase (78 IU/L), and BUN (27.9 mg/ml) levels. The patient received bromocriptine and diazepam to treat his symptoms. 7 days later, the fever disappeared and the patient's serum CPK levels were normalized (175 IU/L). This patient presented with symptoms of neuroleptic malignant syndrome (NMS), thus demonstrating that NMS-like symptoms can occur after combined paroxetine and alprazolam treatment. The adverse drug reaction score obtained by the Naranjo algorithm was 6 in our case, indicating a probable relationship between the patient's NMS-like adverse symptoms and the combined treatment used in this case. The involvement of physiologic and environmental aspects specific to this patient was suspected. Several risk factors for NMS should be noted in elderly depressive patients whose symptoms often include dehydration, agitation, malnutrition, and exhaustion. Careful therapeutic intervention is necessary in cases involving elderly patients who suffer from depression.
16720068	9	39	neuroleptic malignant syndrome	Disease	D009459
16720068	78	88	paroxetine	Chemical	D017374
16720068	93	103	alprazolam	Chemical	D000525
16720068	128	147	depressive symptoms	Disease	D003866
16720068	166	177	psychiatric	Disease	D001523
16720068	194	202	insomnia	Disease	D007319
16720068	204	220	loss of appetite	Disease	D001068
16720068	238	247	agitation	Disease	D011595
16720068	306	316	paroxetine	Chemical	D017374
16720068	328	338	alprazolam	Chemical	D000525
16720068	359	369	paroxetine	Chemical	D017374
16720068	374	384	alprazolam	Chemical	D000525
16720068	425	448	psychomotor retardation	Disease	D011596
16720068	477	492	muscle rigidity	Disease	D009127
16720068	498	505	tremors	Disease	D014202
16720068	525	530	fever	Disease	D005334
16720068	625	648	extrapyramidal symptoms	Disease	D001480
16720068	690	698	creatine	Chemical	D003401
16720068	726	735	aspartate	Chemical	D001224
16720068	765	772	alanine	Chemical	D000409
16720068	851	864	bromocriptine	Chemical	D001971
16720068	869	877	diazepam	Chemical	D003975
16720068	919	924	fever	Disease	D005334
16720068	1040	1070	neuroleptic malignant syndrome	Disease	D009459
16720068	1072	1075	NMS	Disease	D009459
16720068	1102	1105	NMS	Disease	D009459
16720068	1145	1155	paroxetine	Chemical	D017374
16720068	1160	1170	alprazolam	Chemical	D000525
16720068	1324	1327	NMS	Disease	D009459
16720068	1518	1521	NMS	Disease	D009459
16720068	1549	1559	depressive	Disease	D003866
16720068	1598	1609	dehydration	Disease	D003681
16720068	1611	1620	agitation	Disease	D011595
16720068	1622	1634	malnutrition	Disease	D044342
16720068	1750	1760	depression	Disease	D003866
16720068	CID	D000525	D009459
16720068	CID	D017374	D009459

16596970|t|Pilocarpine seizures cause age-dependent impairment in auditory location discrimination.
16596970|a|Children who have status epilepticus have continuous or rapidly repeating seizures that may be life-threatening and may cause life-long changes in brain and behavior. The extent to which status epilepticus causes deficits in auditory discrimination is unknown. A naturalistic auditory location discrimination method was used to evaluate this question using an animal model of status epilepticus. Male Sprague-Dawley rats were injected with saline on postnatal day (P) 20, or a convulsant dose of pilocarpine on P20 or P45. Pilocarpine on either day induced status epilepticus; status epilepticus at P45 resulted in CA3 cell loss and spontaneous seizures, whereas P20 rats had no cell loss or spontaneous seizures. Mature rats were trained with sound-source location and sound-silence discriminations. Control (saline P20) rats acquired both discriminations immediately. In status epilepticus (P20) rats, acquisition of the sound-source location discrimination was moderately impaired. Status epilepticus (P45) rats failed to acquire either sound-source location or sound-silence discriminations. Status epilepticus in rat causes an age-dependent, long-term impairment in auditory discrimination. This impairment may explain one cause of impaired auditory location discrimination in humans.
16596970	0	11	Pilocarpine	Chemical	D010862
16596970	12	20	seizures	Disease	D012640
16596970	41	87	impairment in auditory location discrimination	Disease	D001308
16596970	107	125	status epilepticus	Disease	D013226
16596970	163	171	seizures	Disease	D012640
16596970	276	294	status epilepticus	Disease	D013226
16596970	302	337	deficits in auditory discrimination	Disease	D001308
16596970	465	483	status epilepticus	Disease	D013226
16596970	585	596	pilocarpine	Chemical	D010862
16596970	612	623	Pilocarpine	Chemical	D010862
16596970	646	664	status epilepticus	Disease	D013226
16596970	666	684	status epilepticus	Disease	D013226
16596970	734	742	seizures	Disease	D012640
16596970	793	801	seizures	Disease	D012640
16596970	962	980	status epilepticus	Disease	D013226
16596970	1074	1092	Status epilepticus	Disease	D013226
16596970	1185	1203	Status epilepticus	Disease	D013226
16596970	1246	1283	impairment in auditory discrimination	Disease	D001308
16596970	1326	1367	impaired auditory location discrimination	Disease	D001308
16596970	CID	D010862	D013226
16596970	CID	D010862	D001308

16586083|t|Cardiovascular risk with cyclooxygenase inhibitors: general problem with substance specific differences?
16586083|a|Randomised clinical trials and observational studies have shown an increased risk of myocardial infarction, stroke, hypertension and heart failure during treatment with cyclooxygenase inhibitors. Adverse cardiovascular effects occurred mainly, but not exclusively, in patients with concomitant risk factors. Cyclooxygenase inhibitors cause complex changes in renal, vascular and cardiac prostanoid profiles thereby increasing vascular resistance and fluid retention. The incidence of cardiovascular adverse events tends to increase with the daily dose and total exposure time. A comparison of individual selective and unselective cyclooxygenase inhibitors suggests substance-specific differences, which may depend on differences in pharmacokinetic parameters or inhibitory potency and may be contributed by prostaglandin-independent effects. Diagnostic markers such as N-terminal pro brain natriuretic peptide (NT-proBNP) or high-sensitive C-reactive protein might help in the early identification of patients at risk, thus avoiding the occurrence of serious cardiovascular toxicity.
16586083	25	50	cyclooxygenase inhibitors	Chemical	D016861
16586083	190	211	myocardial infarction	Disease	D009203
16586083	213	219	stroke	Disease	D020521
16586083	221	233	hypertension	Disease	D006973
16586083	238	251	heart failure	Disease	D006333
16586083	274	299	cyclooxygenase inhibitors	Chemical	D016861
16586083	413	438	Cyclooxygenase inhibitors	Chemical	D016861
16586083	735	760	cyclooxygenase inhibitors	Chemical	D016861
16586083	912	925	prostaglandin	Chemical	D011453
16586083	974	1014	N-terminal pro brain natriuretic peptide	Chemical	C109794
16586083	1016	1025	NT-proBNP	Chemical	C109794
16586083	1164	1187	cardiovascular toxicity	Disease	D002318
16586083	CID	D016861	D006973
16586083	CID	D016861	D020521
16586083	CID	D016861	D009203
16586083	CID	D016861	D006333

10539815|t|Predictors of decreased renal function in patients with heart failure during angiotensin-converting enzyme inhibitor therapy: results from the studies of left ventricular dysfunction (SOLVD)
10539815|a|BACKGROUND: Although angiotensin-converting enzyme inhibitor therapy reduces mortality rates in patients with congestive heart failure (CHF), it may also cause decreased renal function. Little information is available to predict which patients are at highest risk for this complication. OBJECTIVE: To quantify specific clinical predictors of reduction in renal function in patients with CHF who are prescribed angiotensin-converting enzyme inhibitor therapy. METHOD: We analyzed data from the Studies of Left Ventricular Dysfunction (SOLVD), a randomized, double-blind, placebo-controlled trial of enalapril for the treatment of CHF. There were 3379 patients randomly assigned to enalapril with a median follow-up of 974 days and 3379 patients randomly assigned to placebo with a mean follow-up of 967 days. Decreased renal function was defined as a rise in serum creatinine >/=0.5 mg/dL (44 micromol/L) from baseline. We used time-to-event analysis to identify potential predictors of decrease in renal function including age, baseline ejection fraction, baseline creatinine, low systolic blood pressure (<100 mm Hg), history of hypertension, diabetes, and use of antiplatelet, diuretic, and beta-blocker therapy. RESULTS: Patients randomly assigned to enalapril had a 33% greater likelihood of decreased renal function than controls (P =.003). By multivariate analysis, in both the placebo and enalapril groups older age, diuretic therapy, and diabetes were associated with decreased renal function, whereas beta-blocker therapy and higher ejection fraction were renoprotective. Older age was associated with a greater risk of developing decreased renal function in both groups, but significantly more so in the enalapril group (enalapril: risk ratio [RR] 1.42 per 10 years, 95% confidence interval [CI] 1.32-1.52 with enalapril; placebo: RR 1.18, 95% CI 1.12-1.25). Diuretic therapy was likewise associated with a greater risk of decreased renal function in the enalapril group (RR 1.89, 95% CI 1.70-2.08) than in the placebo group (RR 1.35, 95% CI 1.09-1.66). Conversely, enalapril had a relative renoprotective effect (RR 1.33, 95% CI 1.13-1.53) compared with placebo (RR 1.96, 95% CI 1.57-2.44) in patients with diabetes. A lower risk of renal impairment was seen in both groups with beta-blocker therapy (RR 0.70, 95% CI 0.57-0.85) and higher baseline ejection fraction (RR 0.93 per 5% increment, 95% CI 0.91-0. 96). CONCLUSIONS: Enalapril use caused a 33% increase in the risk of decreased renal function in patients with CHF. Diuretic use and advanced age increased this risk. Diabetes was associated with an increased risk of renal impairment in all patients with CHF, but this risk was reduced in the enalapril group compared with the placebo group. beta-Blocker therapy and higher ejection fraction were renoprotective in all patients regardless of therapy.
10539815	14	38	decreased renal function	Disease	D051437
10539815	56	69	heart failure	Disease	D006333
10539815	77	88	angiotensin	Chemical	D000809
10539815	154	182	left ventricular dysfunction	Disease	D018487
10539815	212	223	angiotensin	Chemical	D000809
10539815	301	325	congestive heart failure	Disease	D006333
10539815	327	330	CHF	Disease	D006333
10539815	351	375	decreased renal function	Disease	D051437
10539815	533	560	reduction in renal function	Disease	D051437
10539815	578	581	CHF	Disease	D006333
10539815	601	612	angiotensin	Chemical	D000809
10539815	695	723	Left Ventricular Dysfunction	Disease	D018487
10539815	789	798	enalapril	Chemical	D004656
10539815	820	823	CHF	Disease	D006333
10539815	871	880	enalapril	Chemical	D004656
10539815	999	1023	Decreased renal function	Disease	D051437
10539815	1055	1065	creatinine	Chemical	D003404
10539815	1256	1266	creatinine	Chemical	D003404
10539815	1321	1333	hypertension	Disease	D006973
10539815	1335	1343	diabetes	Disease	D003920
10539815	1370	1378	diuretic	Chemical	D004232
10539815	1445	1454	enalapril	Chemical	D004656
10539815	1487	1511	decreased renal function	Disease	D051437
10539815	1587	1596	enalapril	Chemical	D004656
10539815	1615	1623	diuretic	Chemical	D004232
10539815	1637	1645	diabetes	Disease	D003920
10539815	1667	1691	decreased renal function	Disease	D051437
10539815	1831	1855	decreased renal function	Disease	D051437
10539815	1905	1914	enalapril	Chemical	D004656
10539815	1922	1931	enalapril	Chemical	D004656
10539815	2012	2021	enalapril	Chemical	D004656
10539815	2060	2068	Diuretic	Chemical	D004232
10539815	2124	2148	decreased renal function	Disease	D051437
10539815	2156	2165	enalapril	Chemical	D004656
10539815	2267	2276	enalapril	Chemical	D004656
10539815	2409	2417	diabetes	Disease	D003920
10539815	2435	2451	renal impairment	Disease	D051437
10539815	2628	2637	Enalapril	Chemical	D004656
10539815	2679	2703	decreased renal function	Disease	D051437
10539815	2721	2724	CHF	Disease	D006333
10539815	2726	2734	Diuretic	Chemical	D004232
10539815	2777	2785	Diabetes	Disease	D003920
10539815	2827	2843	renal impairment	Disease	D051437
10539815	2865	2868	CHF	Disease	D006333
10539815	2903	2912	enalapril	Chemical	D004656
10539815	CID	D004656	D051437
10539815	CID	D004232	D051437

9022662|t|Pemoline induced acute choreoathetosis: case report and review of the literature.
9022662|a|BACKGROUND: Pemoline is an oxazolidine derivative that is structurally different from amphetamines and used in the treatment of attention deficit disorder. Pemoline has not been commonly associated in the literature as a cause of acute movement disorders. The following case describes two children acutely poisoned with pemoline who experienced profound choreoathetosis. CASE REPORT: Two, 3-year-old male, identical twin siblings presented to the emergency department after found playing with a an empty bottle of pemoline originally containing 59 tablets. The children had a medical history significant for attention deficit disorder previously treated with methylphenidate without success. This was their first day of pemoline therapy. The choreoathetoid movements began 45 min to 1 h after ingestion. The children gave no history of prior movement disorders and there was no family history of movement disorders. The children received gastrointestinal decontamination and high doses of intravenous benzodiazepines in an attempt to control the choreoathetoid movements. Despite treatment, the children continued to have choreoathetosis for approximately 24 hours. Forty-eight hours after admission, the children appeared to be at their baseline and were discharged home. CONCLUSION: Pemoline associated movement disorder has been rarely reported in the acute toxicology literature. The possibility of choreoathetoid movements should be considered in patients presenting after pemoline overdose.
9022662	0	8	Pemoline	Chemical	D010389
9022662	23	38	choreoathetosis	Disease	D002819|D001264
9022662	94	102	Pemoline	Chemical	D010389
9022662	109	120	oxazolidine	Chemical	C064210
9022662	168	180	amphetamines	Chemical	D000662
9022662	210	236	attention deficit disorder	Disease	D001289
9022662	238	246	Pemoline	Chemical	D010389
9022662	318	336	movement disorders	Disease	D009069
9022662	402	410	pemoline	Chemical	D010389
9022662	436	451	choreoathetosis	Disease	D002819|D001264
9022662	596	604	pemoline	Chemical	D010389
9022662	690	716	attention deficit disorder	Disease	D001289
9022662	741	756	methylphenidate	Chemical	D008774
9022662	802	810	pemoline	Chemical	D010389
9022662	824	838	choreoathetoid	Disease	D002819|D001264
9022662	924	942	movement disorders	Disease	D009069
9022662	978	996	movement disorders	Disease	D009069
9022662	1083	1098	benzodiazepines	Chemical	D001569
9022662	1128	1142	choreoathetoid	Disease	D002819|D001264
9022662	1204	1219	choreoathetosis	Disease	D002819|D001264
9022662	1367	1375	Pemoline	Chemical	D010389
9022662	1387	1404	movement disorder	Disease	D009069
9022662	1485	1499	choreoathetoid	Disease	D002819|D001264
9022662	1560	1568	pemoline	Chemical	D010389
9022662	1569	1577	overdose	Disease	D062787
9022662	CID	D010389	D062787
9022662	CID	D010389	D001264
9022662	CID	D010389	D002819

8677458|t|Continuous subcutaneous administration of mesna to prevent ifosfamide-induced hemorrhagic cystitis.
8677458|a|Hemorrhagic cystitis is a major potential toxicity of ifosfamide that can be prevented by administering mesna along with the cytotoxic agent. Mesna is generally administered by the intravenous route, although experience with oral delivery of the drug has increased. The continuous subcutaneous administration of mesna has the advantage of not requiring intravenous access. In addition, subcutaneous delivery of the neutralizing agent will not be associated with the risk of inadequate urinary mesna concentrations, such as in a patient taking oral mesna who experiences severe ifosfamide-induced emesis and is unable to absorb the drug. Limited clinical experience with continuous subcutaneous mesna administration suggests it is a safe, practical, and economic method of drug delivery that permits ifosfamide to be administered successfully in the outpatient setting.
8677458	42	47	mesna	Chemical	D015080
8677458	59	69	ifosfamide	Chemical	D007069
8677458	78	98	hemorrhagic cystitis	Disease	D006470|D003556	hemorrhagic|cystitis
8677458	100	120	Hemorrhagic cystitis	Disease	D006470|D003556	Hemorrhagic|cystitis
8677458	142	150	toxicity	Disease	D064420
8677458	154	164	ifosfamide	Chemical	D007069
8677458	204	209	mesna	Chemical	D015080
8677458	242	247	Mesna	Chemical	D015080
8677458	412	417	mesna	Chemical	D015080
8677458	593	598	mesna	Chemical	D015080
8677458	648	653	mesna	Chemical	D015080
8677458	677	687	ifosfamide	Chemical	D007069
8677458	696	702	emesis	Disease	D014839
8677458	794	799	mesna	Chemical	D015080
8677458	899	909	ifosfamide	Chemical	D007069
8677458	CID	D007069	D003556
8677458	CID	D015080	D006470
8677458	CID	D015080	D003556
8677458	CID	D007069	D006470

6323692|t|Modification of drug action by hyperammonemia.
6323692|a|Pretreatment with ammonium acetate (NH4Ac) (6 mmol/kg s.c.) approximately doubled the time morphine-treated mice remained on a hot surface and similarly increased muscular incoordination by diazepam, but NH4Ac treatment alone had no effect. Thus, hyperammonemia is capable of altering drug action and must be considered along with impaired drug metabolism in enhanced drug responses associated with liver disease. Experiments in vitro showed that acetylcholine-induced catecholamine release from bovine adrenal medulla is depressed as much as 50% by 0.3 mM NH4Ac and KCl-induced contractions of guinea-pig ileum were inhibited 20% by 5 mM NH4Ac. Addition of excess calcium reversed the depression in both tissues, but calcium-independent catecholamine release by acetaldehyde was not blocked by NH4Ac. These results suggested that ammonia blocks calcium channels. Parallels in the actions of NH4Ac and the calcium channel blocker verapamil support this concept. Both verapamil (10 mg/kg i.p.) and NH4Ac pretreatment enhanced morphine analgesia- and diazepam-induced muscular incoordination and antagonized amphetamine-induced motor activity, and neither verapamil nor NH4Ac affected the convulsant action of metrazol. The data suggest that hyperammonemia exerts a calcium channel blocking action which enhances the effects of central nervous system depressants and certain opioid analgesics.
6323692	31	45	hyperammonemia	Disease	D022124
6323692	65	81	ammonium acetate	Chemical	C018824
6323692	83	88	NH4Ac	Chemical	C018824
6323692	138	146	morphine	Chemical	D009020
6323692	219	233	incoordination	Disease	D001259
6323692	237	245	diazepam	Chemical	D003975
6323692	251	256	NH4Ac	Chemical	C018824
6323692	294	308	hyperammonemia	Disease	D022124
6323692	446	459	liver disease	Disease	D008107
6323692	494	507	acetylcholine	Chemical	D000109
6323692	516	529	catecholamine	Chemical	D002395
6323692	604	609	NH4Ac	Chemical	C018824
6323692	614	617	KCl	Chemical	D011189
6323692	686	691	NH4Ac	Chemical	C018824
6323692	712	719	calcium	Chemical	D002118
6323692	733	743	depression	Disease	D003866
6323692	765	772	calcium	Chemical	D002118
6323692	785	798	catecholamine	Chemical	D002395
6323692	810	822	acetaldehyde	Chemical	D000079
6323692	842	847	NH4Ac	Chemical	C018824
6323692	878	885	ammonia	Chemical	D000641
6323692	893	900	calcium	Chemical	D002118
6323692	939	944	NH4Ac	Chemical	C018824
6323692	953	960	calcium	Chemical	D002118
6323692	977	986	verapamil	Chemical	D014700
6323692	1014	1023	verapamil	Chemical	D014700
6323692	1044	1049	NH4Ac	Chemical	C018824
6323692	1072	1080	morphine	Chemical	D009020
6323692	1081	1090	analgesia	Disease	D000699
6323692	1096	1104	diazepam	Chemical	D003975
6323692	1122	1136	incoordination	Disease	D001259
6323692	1153	1164	amphetamine	Chemical	D000661
6323692	1201	1210	verapamil	Chemical	D014700
6323692	1215	1220	NH4Ac	Chemical	C018824
6323692	1255	1263	metrazol	Chemical	D010433
6323692	1287	1301	hyperammonemia	Disease	D022124
6323692	1311	1318	calcium	Chemical	D002118
6323692	CID	D003975	D001259
6323692	CID	C018824	D001259

20195852|t|Risk of nephropathy after consumption of nonionic contrast media by children undergoing cardiac angiography: a prospective study.
20195852|a|Despite increasing reports on nonionic contrast media-induced nephropathy (CIN) in hospitalized adult patients during cardiac procedures, the studies in pediatrics are limited, with even less focus on possible predisposing factors and preventive measures for patients undergoing cardiac angiography. This prospective study determined the incidence of CIN for two nonionic contrast media (CM), iopromide and iohexol, among 80 patients younger than 18 years and compared the rates for this complication in relation to the type and dosage of CM and the presence of cyanosis. The 80 patients in the study consecutively received either iopromide (group A, n = 40) or iohexol (group B, n = 40). Serum sodium (Na), potassium (K), and creatinine (Cr) were measured 24 h before angiography as baseline values, then measured again at 12-, 24-, and 48-h intervals after CM use. Urine samples for Na and Cr also were checked at the same intervals. Risk of renal failure, Injury to the kidney, Failure of kidney function, Loss of kidney function, and End-stage renal damage (RIFLE criteria) were used to define CIN and its incidence in the study population. Accordingly, among the 15 CIN patients (18.75%), 7.5% of the patients in group A had increased risk and 3.75% had renal injury, whereas 5% of group B had increased risk and 2.5% had renal injury. Whereas 33.3% of the patients with CIN were among those who received the proper dosage of CM, the percentage increased to 66.6% among those who received larger doses, with a significant difference in the incidence of CIN related to the different dosages of CM (p = 0.014). Among the 15 patients with CIN, 6 had cyanotic congenital heart diseases, but the incidence did not differ significantly from that for the noncyanotic patients (p = 0.243). Although clinically silent, CIN is not rare in pediatrics. The incidence depends on dosage but not on the type of consumed nonionic CM, nor on the presence of cyanosis, and although CIN usually is reversible, more concern is needed for the prevention of such a complication in children.
20195852	8	19	nephropathy	Disease	D007674
20195852	50	64	contrast media	Chemical	D003287
20195852	169	183	contrast media	Chemical	D003287
20195852	192	203	nephropathy	Disease	D007674
20195852	205	208	CIN	Disease	D007674
20195852	481	484	CIN	Disease	D007674
20195852	502	516	contrast media	Chemical	D003287
20195852	518	520	CM	Chemical	D003287
20195852	523	532	iopromide	Chemical	C038192
20195852	537	544	iohexol	Chemical	D007472
20195852	669	671	CM	Chemical	D003287
20195852	692	700	cyanosis	Disease	D003490
20195852	761	770	iopromide	Chemical	C038192
20195852	792	799	iohexol	Chemical	D007472
20195852	825	831	sodium	Chemical	D012964
20195852	833	835	Na	Chemical	D012964
20195852	838	847	potassium	Chemical	D011188
20195852	849	850	K	Chemical	D011188
20195852	857	867	creatinine	Chemical	D003404
20195852	869	871	Cr	Chemical	D003404
20195852	989	991	CM	Chemical	D003287
20195852	1015	1017	Na	Chemical	D012964
20195852	1022	1024	Cr	Chemical	D003404
20195852	1074	1087	renal failure	Disease	D051437
20195852	1089	1109	Injury to the kidney	Disease	D058186
20195852	1111	1137	Failure of kidney function	Disease	D051437
20195852	1139	1162	Loss of kidney function	Disease	D051437
20195852	1178	1190	renal damage	Disease	D007674
20195852	1228	1231	CIN	Disease	D007674
20195852	1301	1304	CIN	Disease	D007674
20195852	1389	1401	renal injury	Disease	D058186
20195852	1457	1469	renal injury	Disease	D058186
20195852	1506	1509	CIN	Disease	D007674
20195852	1561	1563	CM	Chemical	D003287
20195852	1688	1691	CIN	Disease	D007674
20195852	1728	1730	CM	Chemical	D003287
20195852	1771	1774	CIN	Disease	D007674
20195852	1791	1816	congenital heart diseases	Disease	D006331
20195852	1945	1948	CIN	Disease	D007674
20195852	2049	2051	CM	Chemical	D003287
20195852	2076	2084	cyanosis	Disease	D003490
20195852	2099	2102	CIN	Disease	D007674
20195852	CID	D003287	D007674
20195852	CID	C038192	D007674
20195852	CID	D007472	D007674

18997632|t|A case of ventricular tachycardia related to caffeine pretreatment.
18997632|a|Suboptimal seizure duration is commonly encountered in electroconvulsive therapy practice, especially in older patients with higher seizure thresholds. Intravenous caffeine is commonly used to improve seizure duration and quality in such patients and is generally well tolerated aside from occasional reports of relatively benign ventricular ectopy. We describe a patient with no previous history of cardiac disease or arrhythmia who developed sustained bigeminy and 2 brief runs of ventricular tachycardia after caffeine administration. Although intravenous caffeine is generally well tolerated, the clinician should be aware of the potential for unpredictable and serious ventricular arrhythmias.
18997632	10	33	ventricular tachycardia	Disease	D017180
18997632	45	53	caffeine	Chemical	D002110
18997632	79	86	seizure	Disease	D012640
18997632	200	207	seizure	Disease	D012640
18997632	232	240	caffeine	Chemical	D002110
18997632	269	276	seizure	Disease	D012640
18997632	398	416	ventricular ectopy	Disease	D018879
18997632	468	483	cardiac disease	Disease	D006331
18997632	487	497	arrhythmia	Disease	D001145
18997632	551	574	ventricular tachycardia	Disease	D017180
18997632	581	589	caffeine	Chemical	D002110
18997632	627	635	caffeine	Chemical	D002110
18997632	742	765	ventricular arrhythmias	Disease	D001145
18997632	CID	D002110	D012640
18997632	CID	D002110	D017180
18997632	CID	D002110	D018879

15565293|t|Optical coherence tomography can measure axonal loss in patients with ethambutol-induced optic neuropathy.
15565293|a|PURPOSE: To map and identify the pattern, in vivo, of axonal degeneration in ethambutol-induced optic neuropathy using optical coherence tomography (OCT). Ethambutol is an antimycobacterial agent often used to treat tuberculosis. A serious complication of ethambutol is an optic neuropathy that impairs visual acuity, contrast sensitivity, and color vision. However, early on, when the toxic optic neuropathy is mild and partly reversible, the funduscopic findings are often subtle and easy to miss. METHODS: Three subjects with a history of ethambutol (EMB)-induced optic neuropathy of short-, intermediate-, and long-term visual deficits were administered a full neuro-ophthalmologic examination including visual acuity, color vision, contrast sensitivity, and fundus examination. In addition, OCT (OCT 3000, Humphrey-Zeiss, Dublin, CA) was performed on both eyes of each subject using the retinal nerve fiber layer (RNFL) analysis protocol. OCT interpolates data from 100 points around the optic nerve to effectively map out the RNFL. RESULTS: The results were compared to the calculated average RNFL of normal eyes accumulated from four prior studies using OCT, n=661. In all subjects with history of EMB-induced optic neuropathy, there was a mean loss of 72% nerve fiber layer thickness in the temporal quadrant (patient A, with eventual recovery of visual acuity and fields, 58% loss; patient B, with intermediate visual deficits, 68% loss; patient C, with chronic visual deficits, 90% loss), with an average mean optic nerve thickness of 26+/-16 microm. There was a combined mean loss of 46% of fibers from the superior, inferior, and nasal quadrants in the (six) eyes of all three subjects (mean average thickness of 55+/-29 microm). In both sets (four) of eyes of the subjects with persistent visual deficits (patients B and C), there was an average loss of 79% of nerve fiber thickness in the temporal quadrant. CONCLUSIONS: The OCT results in these patients with EMB-induced optic neuropathy show considerable loss especially of the temporal fibers. This is consistent with prior histopathological studies that show predominant loss of parvo-cellular axons (or small-caliber axons) within the papillo-macular bundle in toxic or hereditary optic neuropathies. OCT can be a valuable tool in the quantitative analysis of optic neuropathies. Additionally, in terms of management of EMB-induced optic neuropathy, it is important to properly manage ethambutol dosing in patients with renal impairment and to achieve proper transition to a maintenance dose once an appropriate loading dose has been reached.
15565293	70	80	ethambutol	Chemical	D004977
15565293	89	105	optic neuropathy	Disease	D009901
15565293	161	180	axonal degeneration	Disease	D009410
15565293	184	194	ethambutol	Chemical	D004977
15565293	203	219	optic neuropathy	Disease	D009901
15565293	262	272	Ethambutol	Chemical	D004977
15565293	323	335	tuberculosis	Disease	D014376
15565293	363	373	ethambutol	Chemical	D004977
15565293	380	396	optic neuropathy	Disease	D009901
15565293	499	515	optic neuropathy	Disease	D009901
15565293	649	659	ethambutol	Chemical	D004977
15565293	661	664	EMB	Chemical	D004977
15565293	674	690	optic neuropathy	Disease	D009901
15565293	731	746	visual deficits	Disease	D014786
15565293	1312	1315	EMB	Chemical	D004977
15565293	1324	1340	optic neuropathy	Disease	D009901
15565293	1527	1542	visual deficits	Disease	D014786
15565293	1578	1593	visual deficits	Disease	D014786
15565293	1909	1924	visual deficits	Disease	D014786
15565293	2081	2084	EMB	Chemical	D004977
15565293	2093	2109	optic neuropathy	Disease	D009901
15565293	2357	2375	optic neuropathies	Disease	D009901
15565293	2436	2454	optic neuropathies	Disease	D009901
15565293	2496	2499	EMB	Chemical	D004977
15565293	2508	2524	optic neuropathy	Disease	D009901
15565293	2561	2571	ethambutol	Chemical	D004977
15565293	2596	2612	renal impairment	Disease	D051437
15565293	CID	D004977	D014786
15565293	CID	D004977	D009901

15266215|t|Effects of the cyclooxygenase-2 specific inhibitor valdecoxib versus nonsteroidal antiinflammatory agents and placebo on cardiovascular thrombotic events in patients with arthritis.
15266215|a|There have been concerns that the risk of cardiovascular thrombotic events may be higher with cyclooxygenase (COX)-2-specific inhibitors than nonselective nonsteroidal antiinflammatory drugs (NSAIDs). We evaluated cardiovascular event data for valdecoxib, a new COX-2-specific inhibitor in approximately 8000 patients with osteoarthritis and rheumatoid arthritis treated with this agent in randomized clinical trials. The incidence of cardiovascular thrombotic events (cardiac, cerebrovascular and peripheral vascular, or arterial thrombotic) was determined by analyzing pooled valdecoxib (10-80 mg daily), nonselective NSAID (diclofenac 75 mg bid, ibuprofen 800 mg tid, or naproxen 500 mg bid) and placebo data from 10 randomized osteoarthritis and rheumatoid arthritis trials that were 6-52 weeks in duration. The incidence rates of events were determined in all patients (n = 7934) and in users of low-dose (< or =325 mg daily) aspirin (n = 1051) and nonusers of aspirin (n = 6883). Crude and exposure-adjusted incidences of thrombotic events were similar for valdecoxib, NSAIDs, and placebo. The risk of serious thrombotic events was also similar for each valdecoxib dose. Thrombotic risk was consistently higher for users of aspirin users than nonusers of aspirin (placebo, 1.4% vs. 0%; valdecoxib, 1.7% vs. 0.2%; NSAIDs, 1.9% vs. 0.5%). The rates of events in users of aspirin were similar for all 3 treatment groups and across valdecoxib doses. Short- and intermediate-term treatment with therapeutic (10 or 20 mg daily) and supratherapeutic (40 or 80 mg daily) valdecoxib doses was not associated with an increased incidence of thrombotic events relative to nonselective NSAIDs or placebo in osteoarthritis and rheumatoid arthritis patients in controlled clinical trials.
15266215	51	61	valdecoxib	Chemical	C406224
15266215	136	146	thrombotic	Disease	D013927
15266215	171	180	arthritis	Disease	D001168
15266215	239	249	thrombotic	Disease	D013927
15266215	426	436	valdecoxib	Chemical	C406224
15266215	505	519	osteoarthritis	Disease	D010003
15266215	524	544	rheumatoid arthritis	Disease	D001172
15266215	632	642	thrombotic	Disease	D013927
15266215	713	723	thrombotic	Disease	D013927
15266215	760	770	valdecoxib	Chemical	C406224
15266215	809	819	diclofenac	Chemical	D004008
15266215	831	840	ibuprofen	Chemical	D007052
15266215	856	864	naproxen	Chemical	D009288
15266215	913	927	osteoarthritis	Disease	D010003
15266215	932	952	rheumatoid arthritis	Disease	D001172
15266215	1113	1120	aspirin	Chemical	D001241
15266215	1148	1155	aspirin	Chemical	D001241
15266215	1210	1220	thrombotic	Disease	D013927
15266215	1245	1255	valdecoxib	Chemical	C406224
15266215	1298	1308	thrombotic	Disease	D013927
15266215	1342	1352	valdecoxib	Chemical	C406224
15266215	1359	1369	Thrombotic	Disease	D013927
15266215	1412	1419	aspirin	Chemical	D001241
15266215	1443	1450	aspirin	Chemical	D001241
15266215	1474	1484	valdecoxib	Chemical	C406224
15266215	1557	1564	aspirin	Chemical	D001241
15266215	1616	1626	valdecoxib	Chemical	C406224
15266215	1751	1761	valdecoxib	Chemical	C406224
15266215	1818	1828	thrombotic	Disease	D013927
15266215	1882	1896	osteoarthritis	Disease	D010003
15266215	1901	1921	rheumatoid arthritis	Disease	D001172
15266215	CID	D001241	D013927

14742097|t|A randomized, placebo-controlled, crossover study of ephedrine for SSRI-induced female sexual dysfunction.
14742097|a|The objective of this study was to determine whether ephedrine, an alpha- and beta-adrenergic agonist previously shown to enhance genital blood flow in women, has beneficial effects in reversing antidepressant-induced sexual dysfunction. Nineteen sexually dysfunctional women receiving either fluoxetine, sertraline, or paroxetine participated in an eight-week, double-blind, placebo-controlled, cross-over study of the effects of ephedrine (50 mg) on self-report measures of sexual desire, arousal, orgasm, and sexual satisfaction. Although there were significant improvements relative to baseline in sexual desire and orgasm intensity/pleasure on 50 mg ephedrine 1-hr prior to sexual activity, significant improvements in these measures, as well as in sexual arousal and orgasmic ability also were noted with placebo. These findings highlight the importance of conducting placebo-controlled trials for this condition.
14742097	53	62	ephedrine	Chemical	D004809
14742097	87	105	sexual dysfunction	Disease	D020018
14742097	160	169	ephedrine	Chemical	D004809
14742097	325	343	sexual dysfunction	Disease	D020018
14742097	354	376	sexually dysfunctional	Disease	D020018
14742097	400	410	fluoxetine	Chemical	D005473
14742097	412	422	sertraline	Chemical	D020280
14742097	427	437	paroxetine	Chemical	D017374
14742097	538	547	ephedrine	Chemical	D004809
14742097	762	771	ephedrine	Chemical	D004809
14742097	CID	D005473	D020018
14742097	CID	D017374	D020018
14742097	CID	D020280	D020018

11890511|t|Erectile dysfunction occurs following substantia nigra lesions in the rat.
11890511|a|Erectile function was assessed 6 weeks following uni- and bilateral injections of 6-hydroxydopamine in the substantia nigra nucleus of the brain. Behavioral apomorphine-induced penile erections were reduced (5/8) and increased (3/8) in uni- and bilateral lesioned animals. Intracavernous pressures, following electrical stimulation of the cavernous nerve, decreased in lesioned animals. Lesions of the substantia nigra were confirmed by histology. Concentration of dopamine and its metabolites were decreased in the striatum of substantia nigra lesioned rats. Lesions of the substantia nigra are therefore associated with erectile dysfunction in rats and may serve as a model to study erectile dysfunction in Parkinson's disease.
11890511	0	20	Erectile dysfunction	Disease	D007172
11890511	157	174	6-hydroxydopamine	Chemical	D016627
11890511	232	243	apomorphine	Chemical	D001058
11890511	540	548	dopamine	Chemical	D004298
11890511	697	717	erectile dysfunction	Disease	D007172
11890511	760	780	erectile dysfunction	Disease	D007172
11890511	784	803	Parkinson's disease	Disease	D010300
11890511	CID	D016627	D007172

9270571|t|Potential therapeutic use of the selective dopamine D1 receptor agonist, A-86929: an acute study in parkinsonian levodopa-primed monkeys.
9270571|a|The clinical utility of dopamine (DA) D1 receptor agonists in the treatment of Parkinson's disease (PD) is still unclear. The therapeutic use of selective DA D1 receptor agonists such as SKF-82958 (6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzaze pine hydrobromide) and A-77636 ([1R, 3S] 3-[1'-admantyl]-1-aminomethyl-3,4-dihydro-5,6-dihydroxy-1H-2-benzo pyran hydrochloride) seems limited because of their duration of action, which is too short for SKF-82958 (< 1 hr) and too long for A-77636 (> 20 hr, leading to behavioral tolerance). We therefore conducted the present acute dose-response study in four 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-exposed cynomolgus monkeys primed to exhibit levodopa-induced dyskinesias to evaluate the locomotor and dyskinetic effects on challenge with four doses (from 0.03 to 1.0 mg/kg) of A-86929 ([-]-[5aR,11bS]-4,5,5a,6,7,11b-hexahydro-2-propyl-3-thia-5-+ ++azacyclopent-1- ena[c]phenathrene-9-10-diol), a selective and full DA D1-like receptor agonist with an intermediate duration of action. Levodopa and the DA D2-like receptor agonist, LY-171555 ([4aR-trans]-4,4a,5,6,7,8,8a,9-o-dihydro-5n-propyl-2H-pyrazo lo-3-4-quinoline hydrochloride) were also used for comparison. Acute administration of A-86929 was as efficacious in alleviating MPTP-induced parkinsonism as levodopa and LY-171555, but was less likely to reproduce the levodopa-induced dyskinesias in these animals than with either LY-171555 or subsequent challenge of levodopa. Selective stimulation of the DA D1 receptor may provide better integration of neural inputs transmitted to the internal segment of the globus pallidus (referred to as the basal ganglia output) compared with levodopa and selective DA D2 receptor agonist. Potent DA D1 receptor agents with an intermediate duration of efficacy such as A-86929 (approximately 4 hr at higher doses tested) are potential therapeutic tools in PD and merit further attention.
9270571	43	51	dopamine	Chemical	D004298
9270571	73	80	A-86929	Chemical	C095427
9270571	100	112	parkinsonian	Disease	D020734
9270571	113	121	levodopa	Chemical	D007980
9270571	162	170	dopamine	Chemical	D004298
9270571	172	174	DA	Chemical	D004298
9270571	217	236	Parkinson's disease	Disease	D010300
9270571	238	240	PD	Disease	D010300
9270571	293	295	DA	Chemical	D004298
9270571	325	334	SKF-82958	Chemical	C071262
9270571	336	425	6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzaze pine hydrobromide	Chemical	C071262
9270571	431	438	A-77636	Chemical	C079415
9270571	440	535	[1R, 3S] 3-[1'-admantyl]-1-aminomethyl-3,4-dihydro-5,6-dihydroxy-1H-2-benzo pyran hydrochloride	Chemical	C079415
9270571	611	620	SKF-82958	Chemical	C071262
9270571	647	654	A-77636	Chemical	C079415
9270571	768	812	1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine	Chemical	D015632
9270571	814	818	MPTP	Chemical	D015632
9270571	865	873	levodopa	Chemical	D007980
9270571	882	893	dyskinesias	Disease	D004409
9270571	924	934	dyskinetic	Disease	D004409
9270571	1000	1007	A-86929	Chemical	C095427
9270571	1009	1114	[-]-[5aR,11bS]-4,5,5a,6,7,11b-hexahydro-2-propyl-3-thia-5-+ ++azacyclopent-1- ena[c]phenathrene-9-10-diol	Chemical	C095427
9270571	1138	1140	DA	Chemical	D004298
9270571	1207	1215	Levodopa	Chemical	D007980
9270571	1224	1226	DA	Chemical	D004298
9270571	1253	1262	LY-171555	Chemical	C416545
9270571	1264	1354	[4aR-trans]-4,4a,5,6,7,8,8a,9-o-dihydro-5n-propyl-2H-pyrazo lo-3-4-quinoline hydrochloride	Chemical	C416545
9270571	1411	1418	A-86929	Chemical	C095427
9270571	1453	1457	MPTP	Chemical	D015632
9270571	1466	1478	parkinsonism	Disease	D020734
9270571	1482	1490	levodopa	Chemical	D007980
9270571	1495	1504	LY-171555	Chemical	C416545
9270571	1543	1551	levodopa	Chemical	D007980
9270571	1560	1571	dyskinesias	Disease	D004409
9270571	1606	1615	LY-171555	Chemical	C416545
9270571	1643	1651	levodopa	Chemical	D007980
9270571	1682	1684	DA	Chemical	D004298
9270571	1860	1868	levodopa	Chemical	D007980
9270571	1883	1885	DA	Chemical	D004298
9270571	1914	1916	DA	Chemical	D004298
9270571	1986	1993	A-86929	Chemical	C095427
9270571	2073	2075	PD	Disease	D010300
9270571	CID	D007980	D004409
9270571	CID	D015632	D020734

7189975|t|Deaths from local anesthetic-induced convulsions in mice.
7189975|a|Median convulsant (CD50) and median lethal (LD50) doses of three representative local anesthetics were determined in adult mice to evaluate the threat to life of local anesthetic-induced convulsions. The CD50 and LD50, respectively, were 57.7 and 58.7 mg/kg for bupivacaine, 111.0 and 133.1 mg/kg for lidocaine, and 243.4 and 266.5 mg/kg for chloroprocaine. When given intraperitoneally, bupivacaine thus was only about twice as toxic as lidocaine and four times as toxic as chloroprocaine. Convulsions always preceded death, except after precipitous cardiopulmonary arrest from extreme doses. A CD50 dose of local anesthetic (causing convulsions in 50% of mice) was fatal in 90% of bupivacaine-induced seizures, in 57% of the chloroprocaine group, and in 6% of the lidocaine group. The narrow gap between convulsant and lethal doses of local anesthetics indicates that untreated convulsions present much more of a threat to life than heretofore appreciated.
7189975	37	48	convulsions	Disease	D012640
7189975	245	256	convulsions	Disease	D012640
7189975	320	331	bupivacaine	Chemical	D002045
7189975	359	368	lidocaine	Chemical	D008012
7189975	400	414	chloroprocaine	Chemical	C004616
7189975	446	457	bupivacaine	Chemical	D002045
7189975	496	505	lidocaine	Chemical	D008012
7189975	533	547	chloroprocaine	Chemical	C004616
7189975	549	560	Convulsions	Disease	D012640
7189975	609	631	cardiopulmonary arrest	Disease	D006323
7189975	693	704	convulsions	Disease	D012640
7189975	741	752	bupivacaine	Chemical	D002045
7189975	761	769	seizures	Disease	D012640
7189975	785	799	chloroprocaine	Chemical	C004616
7189975	824	833	lidocaine	Chemical	D008012
7189975	938	949	convulsions	Disease	D012640
7189975	CID	D008012	D012640
7189975	CID	C004616	D012640
7189975	CID	D002045	D012640

6415512|t|Myoclonic, atonic, and absence seizures following institution of carbamazepine therapy in children.
6415512|a|Five children, aged 3 to 11 years, treated with carbamazepine for epilepsy, had an acute aberrant reaction characterized by the onset of myoclonic, atypical absence and/or atonic (minor motor) seizures within a few days. When the carbamazepine was discontinued, two of the children returned to their former state very quickly, two had the minor motor seizures resolve in 3 and 6 months, and one had the seizures persist. The child in whom the seizures persisted was later found to have ceroid lipofuscinosis. The other children are doing well on other anticonvulsants.
6415512	0	39	Myoclonic, atonic, and absence seizures	Disease	D004831|D004832	Myoclonic seizures|absence seizures
6415512	65	78	carbamazepine	Chemical	D002220
6415512	148	161	carbamazepine	Chemical	D002220
6415512	166	174	epilepsy	Disease	D004827
6415512	237	301	myoclonic, atypical absence and/or atonic (minor motor) seizures	Disease	D004831|D004832	myoclonic seizures|atypical absence seizures
6415512	330	343	carbamazepine	Chemical	D002220
6415512	451	459	seizures	Disease	D012640
6415512	503	511	seizures	Disease	D012640
6415512	543	551	seizures	Disease	D012640
6415512	586	607	ceroid lipofuscinosis	Disease	D009472
6415512	CID	D002220	D004832
6415512	CID	D002220	D004831

1928887|t|Naloxone reversal of hypotension due to captopril overdose.
1928887|a|The hemodynamic effects of captopril and other angiotensin-converting enzyme inhibitors may be mediated by the endogenous opioid system. The opioid antagonist naloxone has been shown to block or reverse the hypotensive actions of captopril. We report a case of an intentional captopril overdose, manifested by marked hypotension, that resolved promptly with the administration of naloxone. To our knowledge, this is the first reported case of captopril-induced hypotension treated with naloxone. Our experience demonstrates a possible role of naloxone in the reversal of hypotension resulting from captopril.
1928887	0	8	Naloxone	Chemical	D009270
1928887	21	32	hypotension	Disease	D007022
1928887	40	49	captopril	Chemical	D002216
1928887	50	58	overdose	Disease	D062787
1928887	87	96	captopril	Chemical	D002216
1928887	107	147	angiotensin-converting enzyme inhibitors	Chemical	D000806
1928887	219	227	naloxone	Chemical	D009270
1928887	267	278	hypotensive	Disease	D007022
1928887	290	299	captopril	Chemical	D002216
1928887	336	345	captopril	Chemical	D002216
1928887	346	354	overdose	Disease	D062787
1928887	377	388	hypotension	Disease	D007022
1928887	440	448	naloxone	Chemical	D009270
1928887	503	512	captopril	Chemical	D002216
1928887	521	532	hypotension	Disease	D007022
1928887	546	554	naloxone	Chemical	D009270
1928887	603	611	naloxone	Chemical	D009270
1928887	631	642	hypotension	Disease	D007022
1928887	658	667	captopril	Chemical	D002216
1928887	CID	D000806	D007022
1928887	CID	D000806	D062787

1728915|t|Carbamazepine-induced cardiac dysfunction. Characterization of two distinct clinical syndromes.
1728915|a|A patient with sinus bradycardia and atrioventricular block, induced by carbamazepine, prompted an extensive literature review of all previously reported cases. From the analysis of these cases, two distinct forms of carbamazepine-associated cardiac dysfunction emerged. One patient group developed sinus tachycardias in the setting of a massive carbamazepine overdose. The second group consisted almost exclusively of elderly women who developed potentially life-threatening bradyarrhythmias or atrioventricular conduction delay, associated with either therapeutic or modestly elevated carbamazepine serum levels. Because carbamazepine is widely used in the treatment of many neurologic and psychiatric conditions, the recognition of the latter syndrome has important implications for the use of this drug in elderly patients.
1728915	0	13	Carbamazepine	Chemical	D002220
1728915	22	41	cardiac dysfunction	Disease	D006331
1728915	117	128	bradycardia	Disease	D001919
1728915	133	155	atrioventricular block	Disease	D054537
1728915	168	181	carbamazepine	Chemical	D002220
1728915	313	326	carbamazepine	Chemical	D002220
1728915	338	357	cardiac dysfunction	Disease	D006331
1728915	395	413	sinus tachycardias	Disease	D013616
1728915	442	455	carbamazepine	Chemical	D002220
1728915	456	464	overdose	Disease	D062787
1728915	572	588	bradyarrhythmias	Disease	D001919
1728915	592	625	atrioventricular conduction delay	Disease	D054537
1728915	683	696	carbamazepine	Chemical	D002220
1728915	719	732	carbamazepine	Chemical	D002220
1728915	788	799	psychiatric	Disease	D001523
1728915	CID	D002220	D054537
1728915	CID	D002220	D001919
1728915	CID	D002220	D013616

20558148|t|Glutamatergic neurotransmission mediated by NMDA receptors in the inferior colliculus can modulate haloperidol-induced catalepsy.
20558148|a|The inferior colliculus (IC) is primarily involved in the processing of auditory information, but it is distinguished from other auditory nuclei in the brainstem by its connections with structures of the motor system. Functional evidence relating the IC to motor behavior derives from experiments showing that activation of the IC by electrical stimulation or excitatory amino acid microinjection causes freezing, escape-like behavior, and immobility. However, the nature of this immobility is still unclear. The present study examined the influence of excitatory amino acid-mediated mechanisms in the IC on the catalepsy induced by the dopamine receptor blocker haloperidol administered systemically (1 or 0.5 mg/kg) in rats. Haloperidol-induced catalepsy was challenged with prior intracollicular microinjections of glutamate NMDA receptor antagonists, MK-801 (15 or 30 mmol/0.5 microl) and AP7 (10 or 20 nmol/0.5 microl), or of the NMDA receptor agonist N-methyl-d-aspartate (NMDA, 20 or 30 nmol/0.5 microl). The results showed that intracollicular microinjection of MK-801 and AP7 previous to systemic injections of haloperidol significantly attenuated the catalepsy, as indicated by a reduced latency to step down from a horizontal bar. Accordingly, intracollicular microinjection of NMDA increased the latency to step down the bar. These findings suggest that glutamate-mediated mechanisms in the neural circuits at the IC level influence haloperidol-induced catalepsy and participate in the regulation of motor activity.
20558148	44	48	NMDA	Chemical	D016202
20558148	99	110	haloperidol	Chemical	D006220
20558148	119	128	catalepsy	Disease	D002375
20558148	501	511	amino acid	Chemical	D000596
20558148	694	704	amino acid	Chemical	D000596
20558148	742	751	catalepsy	Disease	D002375
20558148	767	775	dopamine	Chemical	D004298
20558148	793	804	haloperidol	Chemical	D006220
20558148	857	868	Haloperidol	Chemical	D006220
20558148	877	886	catalepsy	Disease	D002375
20558148	948	957	glutamate	Chemical	D018698
20558148	958	962	NMDA	Chemical	D016202
20558148	985	991	MK-801	Chemical	D016291
20558148	1023	1026	AP7	Chemical	C031231
20558148	1065	1069	NMDA	Chemical	D016202
20558148	1087	1107	N-methyl-d-aspartate	Chemical	D016202
20558148	1109	1113	NMDA	Chemical	D016202
20558148	1200	1206	MK-801	Chemical	D016291
20558148	1211	1214	AP7	Chemical	C031231
20558148	1250	1261	haloperidol	Chemical	D006220
20558148	1291	1300	catalepsy	Disease	D002375
20558148	1419	1423	NMDA	Chemical	D016202
20558148	1496	1505	glutamate	Chemical	D018698
20558148	1575	1586	haloperidol	Chemical	D006220
20558148	1595	1604	catalepsy	Disease	D002375
20558148	CID	D006220	D002375

19940105|t|Metabotropic glutamate 7 receptor subtype modulates motor symptoms in rodent models of Parkinson's disease.
19940105|a|Metabotropic glutamate (mGlu) receptors modulate synaptic transmission in the central nervous system and represent promising therapeutic targets for symptomatic treatment of Parkinson's disease (PD). Among the eight mGlu receptor subtypes, mGlu7 receptor is prominently expressed in the basal ganglia, but its role in restoring motor function in animal models of PD is not known. The effects of N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride (AMN082), the first selective allosteric activator of mGlu7 receptors, were thus tested in different rodent models of PD. Here, we show that oral (5 mg/kg) or intrastriatal administration (0.1 and 0.5 nmol) of AMN082 reverses haloperidol-induced catalepsy in rats. AMN082 (2.5 and 5 mg/kg) reduces apomorphine-induced rotations in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats. In a more complex task commonly used to evaluate major akinetic symptoms of PD patients, 5 mg/kg AMN082 reverses the increased reaction time to respond to a cue of bilateral 6-OHDA-lesioned rats. In addition, AMN082 reduces the duration of haloperidol-induced catalepsy in a mGlu7 receptor-dependent manner in wild-type but not mGlu7 receptor knockout mice. Higher doses of AMN082 (10 and 20 mg/kg p.o.) have no effect on the same models of PD. Overall these findings suggest that mGlu7 receptor activation can reverse motor dysfunction associated with reduced dopamine activity. Selective ligands of mGlu7 receptor subtypes may thus be considered as promising compounds for the development of antiparkinsonian therapeutic strategies.
19940105	13	22	glutamate	Chemical	D018698
19940105	87	106	Parkinson's disease	Disease	D010300
19940105	121	130	glutamate	Chemical	D018698
19940105	282	301	Parkinson's disease	Disease	D010300
19940105	303	305	PD	Disease	D010300
19940105	471	473	PD	Disease	D010300
19940105	503	554	N,N'-dibenzhydrylethane-1,2-diamine dihydrochloride	Chemical	C507346
19940105	556	562	AMN082	Chemical	C507346
19940105	673	675	PD	Disease	D010300
19940105	765	771	AMN082	Chemical	C507346
19940105	781	792	haloperidol	Chemical	D006220
19940105	801	810	catalepsy	Disease	D002375
19940105	820	826	AMN082	Chemical	C507346
19940105	853	864	apomorphine	Chemical	D001058
19940105	897	914	6-hydroxydopamine	Chemical	D016627
19940105	916	922	6-OHDA	Chemical	D016627
19940105	994	1002	akinetic	Disease	D018476
19940105	1015	1017	PD	Disease	D010300
19940105	1036	1042	AMN082	Chemical	C507346
19940105	1113	1119	6-OHDA	Chemical	D016627
19940105	1148	1154	AMN082	Chemical	C507346
19940105	1179	1190	haloperidol	Chemical	D006220
19940105	1199	1208	catalepsy	Disease	D002375
19940105	1313	1319	AMN082	Chemical	C507346
19940105	1380	1382	PD	Disease	D010300
19940105	1500	1508	dopamine	Chemical	D004298
19940105	CID	D006220	D002375

19923525|t|Nimodipine prevents memory impairment caused by nitroglycerin-induced hypotension in adult mice.
19923525|a|BACKGROUND: Hypotension and a resultant decrease in cerebral blood flow have been implicated in the development of cognitive dysfunction. We tested the hypothesis that nimodipine (NIMO) administered at the onset of nitroglycerin (NTG)-induced hypotension would preserve long-term associative memory. METHODS: The passive avoidance (PA) paradigm was used to assess memory retention. For PA training, latencies (seconds) were recorded for entry from a suspended platform into a Plexiglas tube where a shock was automatically delivered. Latencies were recorded 48 h later for a testing trial. Ninety-six Swiss-Webster mice (30-35 g, 6-8 wk), were randomized into 6 groups 1) saline (control), 2) NTG immediately after learning, 3) NTG 3 h after learning, 4) NTG and NIMO, 5) vehicle, and 6) NIMO alone. The extent of hypotension and changes in brain tissue oxygenation (PbtO(2)) and in cerebral blood flow were studied in a separate group of animals. RESULTS: All groups exhibited similar training latencies (17.0 +/- 4.6 s). Mice subjected to hypotensive episodes showed a significant decrease in latency time (178 +/- 156 s) compared with those injected with saline, NTG + NIMO, or delayed NTG (580 +/- 81 s, 557 +/- 67 s, and 493 +/- 146 s, respectively). A Kruskal-Wallis 1-way analysis of variance indicated a significant difference among the 4 treatment groups (H = 15.34; P < 0.001). In a separate group of mice not subjected to behavioral studies, the same dose of NTG (n = 3) and NTG + NIMO (n = 3) caused mean arterial blood pressure to decrease from 85.9 +/- 3.8 mm Hg sem to 31.6 +/- 0.8 mm Hg sem and from 86.2 +/- 3.7 mm Hg sem to 32.6 +/- 0.2 mm Hg sem, respectively. Mean arterial blood pressure in mice treated with NIMO alone decreased from 88.1 +/- 3.8 mm Hg to 80.0 +/- 2.9 mm Hg. The intergroup difference was statistically significant (P < 0.05). PbtO(2) decreased from 51.7 +/- 4.5 mm Hg sem to 33.8 +/- 5.2 mm Hg sem in the NTG group and from 38.6 +/- 6.1 mm Hg sem to 25.4 +/- 2.0 mm Hg sem in the NTG + NIMO groups, respectively. There were no significant differences among groups. CONCLUSION: In a PA retention paradigm, the injection of NTG immediately after learning produced a significant impairment of long-term associative memory in mice, whereas delayed induced hypotension had no effect. NIMO attenuated the disruption in consolidation of long-term memory caused by NTG but did not improve latency in the absence of hypotension. The observed effect of NIMO may have been attributable to the preservation of calcium homeostasis during hypotension, because there were no differences in the PbtO(2) indices among groups.
19923525	0	10	Nimodipine	Chemical	D009553
19923525	20	37	memory impairment	Disease	D008569
19923525	48	61	nitroglycerin	Chemical	D005996
19923525	70	81	hypotension	Disease	D007022
19923525	109	120	Hypotension	Disease	D007022
19923525	212	233	cognitive dysfunction	Disease	D003072
19923525	265	275	nimodipine	Chemical	D009553
19923525	277	281	NIMO	Chemical	D009553
19923525	312	325	nitroglycerin	Chemical	D005996
19923525	327	330	NTG	Chemical	D005996
19923525	340	351	hypotension	Disease	D007022
19923525	790	793	NTG	Chemical	D005996
19923525	825	828	NTG	Chemical	D005996
19923525	852	855	NTG	Chemical	D005996
19923525	860	864	NIMO	Chemical	D009553
19923525	885	889	NIMO	Chemical	D009553
19923525	911	922	hypotension	Disease	D007022
19923525	1138	1149	hypotensive	Disease	D007022
19923525	1263	1266	NTG	Chemical	D005996
19923525	1269	1273	NIMO	Chemical	D009553
19923525	1286	1289	NTG	Chemical	D005996
19923525	1567	1570	NTG	Chemical	D005996
19923525	1583	1586	NTG	Chemical	D005996
19923525	1589	1593	NIMO	Chemical	D009553
19923525	1827	1831	NIMO	Chemical	D009553
19923525	2042	2045	NTG	Chemical	D005996
19923525	2117	2120	NTG	Chemical	D005996
19923525	2123	2127	NIMO	Chemical	D009553
19923525	2259	2262	NTG	Chemical	D005996
19923525	2389	2400	hypotension	Disease	D007022
19923525	2416	2420	NIMO	Chemical	D009553
19923525	2494	2497	NTG	Chemical	D005996
19923525	2544	2555	hypotension	Disease	D007022
19923525	2580	2584	NIMO	Chemical	D009553
19923525	2635	2642	calcium	Chemical	D002118
19923525	2662	2673	hypotension	Disease	D007022
19923525	CID	D005996	D008569
19923525	CID	D005996	D007022

19058474|t|Fatal haemopericardium and gastrointestinal haemorrhage due to possible interaction of cranberry juice with warfarin.
19058474|a|We report a case of fatal internal haemorrhage in an elderly man who consumed only cranberry juice for two weeks while maintaining his usual dosage of warfarin. We propose that naturally occurring compounds such as flavonoids, which are present in fruit juices, may increase the potency of warfarin by competing for the enzymes that normally inactivate warfarin. While traditionally regarded as foodstuffs, consumption of fruit juices should be considered when patients develop adverse drug reactions.
19058474	6	22	haemopericardium	Disease	D010490
19058474	27	55	gastrointestinal haemorrhage	Disease	D006471
19058474	108	116	warfarin	Chemical	D014859
19058474	153	164	haemorrhage	Disease	D006470
19058474	269	277	warfarin	Chemical	D014859
19058474	333	343	flavonoids	Chemical	D005419
19058474	408	416	warfarin	Chemical	D014859
19058474	471	479	warfarin	Chemical	D014859
19058474	CID	D005419	D006471
19058474	CID	D014859	D006471

18808529|t|Isoproterenol induces primary loss of dystrophin in rat hearts: correlation with myocardial injury.
18808529|a|The mechanism of isoproterenol-induced myocardial damage is unknown, but a mismatch of oxygen supply vs. demand following coronary hypotension and myocardial hyperactivity is the best explanation for the complex morphological alterations observed. Severe alterations in the structural integrity of the sarcolemma of cardiomyocytes have been demonstrated to be caused by isoproterenol. Taking into account that the sarcolemmal integrity is stabilized by the dystrophin-glycoprotein complex (DGC) that connects actin and laminin in contractile machinery and extracellular matrix and by integrins, this study tests the hypothesis that isoproterenol affects sarcolemmal stability through changes in the DGC and integrins. We found different sensitivity of the DGC and integrin to isoproterenol subcutaneous administration. Immunofluorescent staining revealed that dystrophin is the most sensitive among the structures connecting the actin in the cardiomyocyte cytoskeleton and the extracellular matrix. The sarcomeric actin dissolution occurred after the reduction or loss of dystrophin. Subsequently, after lysis of myofilaments, gamma-sarcoglycan, beta-dystroglycan, beta1-integrin, and laminin alpha-2 expressions were reduced followed by their breakdown, as epiphenomena of the myocytolytic process. In conclusion, administration of isoproterenol to rats results in primary loss of dystrophin, the most sensitive among the structural proteins that form the DGC that connects the extracellular matrix and the cytoskeleton in cardiomyocyte. These changes, related to ischaemic injury, explain the severe alterations in the structural integrity of the sarcolemma of cardiomyocytes and hence severe and irreversible injury induced by isoproterenol.
18808529	0	13	Isoproterenol	Chemical	D007545
18808529	81	98	myocardial injury	Disease	D009202
18808529	117	130	isoproterenol	Chemical	D007545
18808529	139	156	myocardial damage	Disease	D009202
18808529	187	193	oxygen	Chemical	D010100
18808529	231	242	hypotension	Disease	D007022
18808529	247	271	myocardial hyperactivity	Disease	D009202
18808529	470	483	isoproterenol	Chemical	D007545
18808529	732	745	isoproterenol	Chemical	D007545
18808529	876	889	isoproterenol	Chemical	D007545
18808529	1433	1446	isoproterenol	Chemical	D007545
18808529	1665	1681	ischaemic injury	Disease	D007511
18808529	1830	1843	isoproterenol	Chemical	D007545
18808529	CID	D007545	D009202
18808529	CID	D007545	D007511

18674790|t|High fat diet-fed obese rats are highly sensitive to doxorubicin-induced cardiotoxicity.
18674790|a|Often, chemotherapy by doxorubicin (Adriamycin) is limited due to life threatening cardiotoxicity in patients during and posttherapy. Recently, we have shown that moderate diet restriction remarkably protects against doxorubicin-induced cardiotoxicity. This cardioprotection is accompanied by decreased cardiac oxidative stress and triglycerides and increased cardiac fatty-acid oxidation, ATP synthesis, and upregulated JAK/STAT3 pathway. In the current study, we investigated whether a physiological intervention by feeding 40% high fat diet (HFD), which induces obesity in male Sprague-Dawley rats (250-275 g), sensitizes to doxorubicin-induced cardiotoxicity. A LD(10) dose (8 mg doxorubicin/kg, ip) administered on day 43 of the HFD feeding regimen led to higher cardiotoxicity, cardiac dysfunction, lipid peroxidation, and 80% mortality in the obese (OB) rats in the absence of any significant renal or hepatic toxicity. Doxorubicin toxicokinetics studies revealed no change in accumulation of doxorubicin and doxorubicinol (toxic metabolite) in the normal diet-fed (ND) and OB hearts. Mechanistic studies revealed that OB rats are sensitized due to: (1) higher oxyradical stress leading to upregulation of uncoupling proteins 2 and 3, (2) downregulation of cardiac peroxisome proliferators activated receptor-alpha, (3) decreased plasma adiponectin levels, (4) decreased cardiac fatty-acid oxidation (666.9+/-14.0 nmol/min/g heart in ND versus 400.2+/-11.8 nmol/min/g heart in OB), (5) decreased mitochondrial AMP-alpha2 protein kinase, and (6) 86% drop in cardiac ATP levels accompanied by decreased ATP/ADP ratio after doxorubicin administration. Decreased cardiac erythropoietin and increased SOCS3 further downregulated the cardioprotective JAK/STAT3 pathway. In conclusion, HFD-induced obese rats are highly sensitized to doxorubicin-induced cardiotoxicity by substantially downregulating cardiac mitochondrial ATP generation, increasing oxidative stress and downregulating the JAK/STAT3 pathway.
18674790	5	8	fat	Chemical	D004041
18674790	18	23	obese	Disease	D009765
18674790	53	64	doxorubicin	Chemical	D004317
18674790	73	87	cardiotoxicity	Disease	D066126
18674790	112	123	doxorubicin	Chemical	D004317
18674790	125	135	Adriamycin	Chemical	D004317
18674790	172	186	cardiotoxicity	Disease	D066126
18674790	306	317	doxorubicin	Chemical	D004317
18674790	326	340	cardiotoxicity	Disease	D066126
18674790	421	434	triglycerides	Chemical	D014280
18674790	479	482	ATP	Chemical	D000255
18674790	624	627	fat	Chemical	D004041
18674790	654	661	obesity	Disease	D009765
18674790	717	728	doxorubicin	Chemical	D004317
18674790	737	751	cardiotoxicity	Disease	D066126
18674790	773	784	doxorubicin	Chemical	D004317
18674790	857	871	cardiotoxicity	Disease	D066126
18674790	873	892	cardiac dysfunction	Disease	D006331
18674790	939	944	obese	Disease	D009765
18674790	946	948	OB	Disease	D009765
18674790	989	1014	renal or hepatic toxicity	Disease	D007674|D056486	renal toxicity|hepatic toxicity
18674790	1016	1027	Doxorubicin	Chemical	D004317
18674790	1089	1100	doxorubicin	Chemical	D004317
18674790	1105	1118	doxorubicinol	Chemical	C010013
18674790	1170	1172	OB	Disease	D009765
18674790	1215	1217	OB	Disease	D009765
18674790	1573	1575	OB	Disease	D009765
18674790	1606	1609	AMP	Chemical	D000249
18674790	1661	1664	ATP	Chemical	D000255
18674790	1697	1700	ATP	Chemical	D000255
18674790	1701	1704	ADP	Chemical	D000244
18674790	1717	1728	doxorubicin	Chemical	D004317
18674790	1887	1892	obese	Disease	D009765
18674790	1923	1934	doxorubicin	Chemical	D004317
18674790	1943	1957	cardiotoxicity	Disease	D066126
18674790	2012	2015	ATP	Chemical	D000255
18674790	CID	D004041	D009765
18674790	CID	D004317	D006331

18441470|t|Complete atrioventricular block secondary to lithium therapy.
18441470|a|Sinus node dysfunction has been reported most frequently among the adverse cardiovascular effects of lithium. In the present case, complete atrioventricular (AV) block with syncopal attacks developed secondary to lithium therapy, necessitating permanent pacemaker implantation. Serum lithium levels remained under or within the therapeutic range during the syncopal attacks. Lithium should be used with extreme caution, especially in patients with mild disturbance of AV conduction.
18441470	9	31	atrioventricular block	Disease	D054537
18441470	45	52	lithium	Chemical	D008094
18441470	62	84	Sinus node dysfunction	Disease	D012804
18441470	163	170	lithium	Chemical	D008094
18441470	202	229	atrioventricular (AV) block	Disease	D054537
18441470	235	251	syncopal attacks	Disease	D013575
18441470	275	282	lithium	Chemical	D008094
18441470	346	353	lithium	Chemical	D008094
18441470	419	435	syncopal attacks	Disease	D013575
18441470	437	444	Lithium	Chemical	D008094
18441470	CID	D008094	D012804
18441470	CID	D008094	D054537

17366349|t|Neuroleptic malignant syndrome induced by ziprasidone on the second day of treatment.
17366349|a|Neuroleptic malignant syndrome (NMS) is the rarest and most serious of the neuroleptic-induced movement disorders. We describe a case of neuroleptic malignant syndrome (NMS) associated with the use of ziprasidone. Although conventional neuroleptics are more frequently associated with NMS, atypical antipsychotic drugs like ziprasidone may also be a cause. The patient is a 24-year-old male with a history of schizophrenia who developed signs and symptoms of NMS after 2 days of treatment with an 80-mg/day dose of orally administrated ziprasidone. This case is the earliest (second day of treatment) NMS due to ziprasidone reported in the literature.
17366349	0	30	Neuroleptic malignant syndrome	Disease	D009459
17366349	42	53	ziprasidone	Chemical	C092292
17366349	86	116	Neuroleptic malignant syndrome	Disease	D009459
17366349	118	121	NMS	Disease	D009459
17366349	181	199	movement disorders	Disease	D009069
17366349	223	253	neuroleptic malignant syndrome	Disease	D009459
17366349	255	258	NMS	Disease	D009459
17366349	287	298	ziprasidone	Chemical	C092292
17366349	371	374	NMS	Disease	D009459
17366349	410	421	ziprasidone	Chemical	C092292
17366349	495	508	schizophrenia	Disease	D012559
17366349	545	548	NMS	Disease	D009459
17366349	622	633	ziprasidone	Chemical	C092292
17366349	687	690	NMS	Disease	D009459
17366349	698	709	ziprasidone	Chemical	C092292
17366349	CID	C092292	D009459

16584858|t|Role of mangiferin on biochemical alterations and antioxidant status in isoproterenol-induced myocardial infarction in rats.
16584858|a|The current study dealt with the protective role of mangiferin, a polyphenol from Mangifera indica Linn. (Anacardiaceae), on isoproterenol (ISPH)-induced myocardial infarction (MI) in rats through its antioxidative mechanism. Subcutaneous injection of ISPH (200 mg/kg body weight in 1 ml saline) to rats for 2 consecutive days caused myocardial damage in rat heart, which was determined by the increased activity of serum lactate dehydrogenase (LDH) and creatine phosphokinase isoenzymes (CK-MB), increased uric acid level and reduced plasma iron binding capacity. The protective role of mangiferin was analyzed by triphenyl tetrazolium chloride (TTC) test used for macroscopic enzyme mapping assay of the ischemic myocardium. The heart tissue antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione transferase and glutathione reductase activities, non-enzymic antioxidants such as cerruloplasmin, Vitamin C, Vitamin E and glutathione levels were altered in MI rats. Upon pretreatment with mangiferin (100 mg/kg body weight suspended in 2 ml of dimethyl sulphoxide) given intraperitoneally for 28 days to MI rats protected the above-mentioned parameters to fall from the normal levels. Activities of heart tissue enzymic antioxidants and serum non-enzymic antioxidants levels rose significantly upon mangiferin administration as compared to ISPH-induced MI rats. From the present study it is concluded that mangiferin exerts a beneficial effect against ISPH-induced MI due to its antioxidant potential, which regulated the tissues defense system against cardiac damage.
16584858	8	18	mangiferin	Chemical	C013592
16584858	72	85	isoproterenol	Chemical	D007545
16584858	94	115	myocardial infarction	Disease	D009203
16584858	177	187	mangiferin	Chemical	C013592
16584858	191	201	polyphenol	Chemical	D059808
16584858	250	263	isoproterenol	Chemical	D007545
16584858	265	269	ISPH	Chemical	D007545
16584858	279	300	myocardial infarction	Disease	D009203
16584858	302	304	MI	Disease	D009203
16584858	377	381	ISPH	Chemical	D007545
16584858	459	476	myocardial damage	Disease	D009202
16584858	547	554	lactate	Chemical	D019344
16584858	579	587	creatine	Chemical	D003401
16584858	632	641	uric acid	Chemical	D014527
16584858	667	671	iron	Chemical	D007501
16584858	713	723	mangiferin	Chemical	C013592
16584858	740	770	triphenyl tetrazolium chloride	Chemical	C009591
16584858	772	775	TTC	Chemical	C009591
16584858	831	850	ischemic myocardium	Disease	D017202
16584858	897	907	superoxide	Chemical	D013481
16584858	929	940	glutathione	Chemical	D005978
16584858	953	964	glutathione	Chemical	D005978
16584858	981	992	glutathione	Chemical	D005978
16584858	1064	1073	Vitamin C	Chemical	D001205
16584858	1075	1084	Vitamin E	Chemical	D014810
16584858	1089	1100	glutathione	Chemical	D005978
16584858	1124	1126	MI	Disease	D009203
16584858	1156	1166	mangiferin	Chemical	C013592
16584858	1211	1230	dimethyl sulphoxide	Chemical	D004121
16584858	1271	1273	MI	Disease	D009203
16584858	1466	1476	mangiferin	Chemical	C013592
16584858	1507	1511	ISPH	Chemical	D007545
16584858	1520	1522	MI	Disease	D009203
16584858	1573	1583	mangiferin	Chemical	C013592
16584858	1619	1623	ISPH	Chemical	D007545
16584858	1632	1634	MI	Disease	D009203
16584858	1720	1734	cardiac damage	Disease	D006331
16584858	CID	D007545	D009203

16563323|t|Remifentanil pretreatment reduces myoclonus after etomidate.
16563323|a|STUDY OBJECTIVE: The aim of the study was to compare the effect of pretreatment with remifentanil 1 microg/kg and the effect of gender on the incidence of myoclonus after anesthesia induction with etomidate. DESIGN: This was a randomized, double-blind study. SETTING: The study was conducted at a university hospital. PATIENTS: Sixty patients were pretreated in a randomized double-blinded fashion with remifentanil 1 microg/kg or placebo. Two minutes after remifentanil or placebo injection, etomidate 0.3 mg/kg was given. MEASUREMENTS: Myoclonus was recorded with a scale of 0 to 3. The grade of sedation (none, mild, moderate, severe), nausea, pruritus, and apnea were recorded after injection of both drugs. MAIN RESULTS: The incidence of myoclonus was significantly lower in the remifentanil group (6.7%) than in the placebo group (70%) (P < 0.001). None of the patients experienced sedation, apnea, nausea, or pruritus after injection of both drugs. In the placebo group, male patients were associated with significantly increased incidence of myoclonus after etomidate administration. CONCLUSION: Pretreatment with remifentanil 1 microg/kg reduced myoclonus after etomidate induction without side effects such as sedation, apnea, nausea, or pruritus. Men experience increased incidence of myoclonus than women after etomidate administration.
16563323	0	12	Remifentanil	Chemical	C071741
16563323	34	43	myoclonus	Disease	D009207
16563323	50	59	etomidate	Chemical	D005045
16563323	146	158	remifentanil	Chemical	C071741
16563323	216	225	myoclonus	Disease	D009207
16563323	258	267	etomidate	Chemical	D005045
16563323	464	476	remifentanil	Chemical	C071741
16563323	519	531	remifentanil	Chemical	C071741
16563323	554	563	etomidate	Chemical	D005045
16563323	599	608	Myoclonus	Disease	D009207
16563323	700	706	nausea	Disease	D009325
16563323	708	716	pruritus	Disease	D011537
16563323	722	727	apnea	Disease	D001049
16563323	804	813	myoclonus	Disease	D009207
16563323	845	857	remifentanil	Chemical	C071741
16563323	959	964	apnea	Disease	D001049
16563323	966	972	nausea	Disease	D009325
16563323	977	985	pruritus	Disease	D011537
16563323	1111	1120	myoclonus	Disease	D009207
16563323	1127	1136	etomidate	Chemical	D005045
16563323	1183	1195	remifentanil	Chemical	C071741
16563323	1216	1225	myoclonus	Disease	D009207
16563323	1232	1241	etomidate	Chemical	D005045
16563323	1291	1296	apnea	Disease	D001049
16563323	1298	1304	nausea	Disease	D009325
16563323	1309	1317	pruritus	Disease	D011537
16563323	1357	1366	myoclonus	Disease	D009207
16563323	1384	1393	etomidate	Chemical	D005045
16563323	CID	D005045	D009207

16428827|t|Daidzein activates choline acetyltransferase from MC-IXC cells and improves drug-induced amnesia.
16428827|a|The choline acetyltransferase (ChAT) activator, which enhances cholinergic transmission via an augmentation of the enzymatic production of acetylcholine (ACh), is an important factor in the treatment of Alzheimer's disease (AD). Methanolic extracts from Pueraria thunbergiana exhibited an activation effect (46%) on ChAT in vitro. Via the sequential isolation of Pueraria thunbergiana, the active component was ultimately identified as daidzein (4',7-dihydroxy-isoflavone). In order to investigate the effects of daidzein from Pueraria thunbergiana on scopolamine-induced impairments of learning and memory, we conducted a series of in vivo tests. Administration of daidzein (4.5 mg/kg body weight) to mice was shown significantly to reverse scopolamine-induced amnesia, according to the results of a Y-maze test. Injections of scopolamine into mice resulted in impaired performance on Y-maze tests (a 37% decreases in alternation behavior). By way of contrast, mice treated with daidzein prior to the scopolamine injections were noticeably protected from this performance impairment (an approximately 12%-21% decrease in alternation behavior). These results indicate that daidzein might play a role in acetylcholine biosynthesis as a ChAT activator, and that it also ameliorates scopolamine-induced amnesia.
16428827	0	8	Daidzein	Chemical	C004742
16428827	19	26	choline	Chemical	D002794
16428827	89	96	amnesia	Disease	D000647
16428827	102	109	choline	Chemical	D002794
16428827	237	250	acetylcholine	Chemical	D000109
16428827	252	255	ACh	Chemical	D000109
16428827	301	320	Alzheimer's disease	Disease	D000544
16428827	322	324	AD	Disease	D000544
16428827	534	542	daidzein	Chemical	C004742
16428827	544	569	4',7-dihydroxy-isoflavone	Chemical	C004742
16428827	611	619	daidzein	Chemical	C004742
16428827	650	661	scopolamine	Chemical	D012601
16428827	670	704	impairments of learning and memory	Disease	D007859|D008569	impairments of learning|impairments of memory
16428827	764	772	daidzein	Chemical	C004742
16428827	840	851	scopolamine	Chemical	D012601
16428827	860	867	amnesia	Disease	D000647
16428827	926	937	scopolamine	Chemical	D012601
16428827	1078	1086	daidzein	Chemical	C004742
16428827	1100	1111	scopolamine	Chemical	D012601
16428827	1271	1279	daidzein	Chemical	C004742
16428827	1301	1314	acetylcholine	Chemical	D000109
16428827	1378	1389	scopolamine	Chemical	D012601
16428827	1398	1405	amnesia	Disease	D000647
16428827	CID	D012601	D000647

15985056|t|Possible azithromycin-associated hiccups.
15985056|a|OBJECTIVE: To report a case of persistent hiccups associated by azithromycin therapy. CASE SUMMARY: A 76-year-old man presented with persistent hiccups after beginning azithromycin for the treatment of pharyngitis. Hiccups were persistent and exhausting. Discontinuation of azithromycin and therapy with baclofen finally resolved hiccups. No organic cause of hiccups was identified despite extensive investigation. DISCUSSION: Pharmacotherapeutic agents have been uncommonly associated with hiccups. Corticosteroids (dexamethasone and methylprednisolone), benzodiazepines (midazolam) and general anaesthesia have been the specific agents mentioned most frequently in the literature as being associated with the development of hiccups. Few cases of drug-induced hiccups have been reported related to macrolide antimicrobials. Using the Naranjo adverse effect reaction probability scale this event could be classified as possible (score 5 points), mostly because of the close temporal sequence, previous reports on this reaction with other macrolides and the absence of any alternative explanation for hiccups. Our hypothesis is that a vagal mechanism mediated by azithromycin could be the pathogenesis of hiccups in our patient. CONCLUSIONS: Diagnosis of drug-induced hiccups is difficult and often achieved only by a process of elimination. However, macrolide antimicrobials have been reported to be associated with hiccups and vagal mechanism could explain the development of this side-effect.
15985056	9	21	azithromycin	Chemical	D017963
15985056	33	40	hiccups	Disease	D006606
15985056	84	91	hiccups	Disease	D006606
15985056	106	118	azithromycin	Chemical	D017963
15985056	186	193	hiccups	Disease	D006606
15985056	210	222	azithromycin	Chemical	D017963
15985056	244	255	pharyngitis	Disease	D010612
15985056	257	264	Hiccups	Disease	D006606
15985056	316	328	azithromycin	Chemical	D017963
15985056	346	354	baclofen	Chemical	D001418
15985056	372	379	hiccups	Disease	D006606
15985056	401	408	hiccups	Disease	D006606
15985056	533	540	hiccups	Disease	D006606
15985056	559	572	dexamethasone	Chemical	D003907
15985056	577	595	methylprednisolone	Chemical	D008775
15985056	598	613	benzodiazepines	Chemical	D001569
15985056	615	624	midazolam	Chemical	D008874
15985056	768	775	hiccups	Disease	D006606
15985056	803	810	hiccups	Disease	D006606
15985056	841	850	macrolide	Chemical	D018942
15985056	1080	1090	macrolides	Chemical	D018942
15985056	1142	1149	hiccups	Disease	D006606
15985056	1204	1216	azithromycin	Chemical	D017963
15985056	1246	1253	hiccups	Disease	D006606
15985056	1309	1316	hiccups	Disease	D006606
15985056	1392	1401	macrolide	Chemical	D018942
15985056	1458	1465	hiccups	Disease	D006606
15985056	CID	D017963	D006606
15985056	CID	D001418	D006606

15276120|t|Time trends in warfarin-associated hemorrhage.
15276120|a|The annual incidence of warfarin-related bleeding at Brigham and Women's Hospital increased from 0.97/1,000 patient admissions in the first time period (January 1995 to October 1998) to 1.19/1,000 patient admissions in the second time period (November 1998 to August 2002) of this study. The proportion of patients with major and intracranial bleeding increased from 20.2% and 1.9%, respectively, in the first time period, to 33.3% and 7.8%, respectively, in the second.
15276120	15	23	warfarin	Chemical	D014859
15276120	35	45	hemorrhage	Disease	D006470
15276120	71	79	warfarin	Chemical	D014859
15276120	88	96	bleeding	Disease	D006470
15276120	377	398	intracranial bleeding	Disease	D020300
15276120	CID	D014859	D020300
15276120	CID	D014859	D006470

11271907|t|Fatal haemorrhagic myocarditis secondary to cyclophosphamide therapy.
11271907|a|Haemorrhagic myocarditis is a rare but important complication of cyclophosphamide therapy. Echocardiographic identification of the disorder can be made. We believe that the ultrasound features of this disorder have not been previously reported.
11271907	6	30	haemorrhagic myocarditis	Disease	D006470|D009205	haemorrhagic|myocarditis
11271907	44	60	cyclophosphamide	Chemical	D003520
11271907	70	94	Haemorrhagic myocarditis	Disease	D006470|D009205	Haemorrhagic|myocarditis
11271907	135	151	cyclophosphamide	Chemical	D003520
11271907	CID	D003520	D009205
11271907	CID	D003520	D006470

10524660|t|Glyceryl trinitrate induces attacks of migraine without aura in sufferers of migraine with aura.
10524660|a|Migraine with aura and migraine without aura have the same pain phase, thus indicating that migraine with aura and migraine without aura share a common pathway of nociception. In recent years, increasing evidence has suggested that the messenger molecule nitric oxide (NO) is involved in pain mechanisms of migraine without aura. In order to clarify whether the same is true for migraine with aura, in the present study we examined the headache response to intravenous infusion of glyceryl trinitrate (GTN) (0.5 microg/kg/min for 20 min) in 12 sufferers of migraine with aura. The specific aim was to elucidate whether an aura and/or an attack of migraine without aura could be induced. Fourteen healthy subjects served as controls. Aura symptoms were not elicited in any subject. Headache was more severe in migraineurs than in the controls during and immediately after GTN infusion (p=0.037) as well as during the following 11 h (p = 0.008). In the controls, the GTN-induced headache gradually disappeared, whereas in migraineurs peak headache intensity occurred at a mean time of 240 min post-infusion. At this time the induced headache in 6 of 12 migraineurs fulfilled the diagnostic criteria for migraine without aura of the International Headache Society. The results therefore suggest that NO is involved in the pain mechanisms of migraine with aura. Since cortical spreading depression has been shown to liberate NO in animals, this finding may help our understanding of the coupling between cortical spreading depression and headache in migraine with aura.
10524660	0	19	Glyceryl trinitrate	Chemical	D005996
10524660	39	60	migraine without aura	Disease	D020326
10524660	77	95	migraine with aura	Disease	D020325
10524660	97	115	Migraine with aura	Disease	D020325
10524660	120	141	migraine without aura	Disease	D020326
10524660	156	160	pain	Disease	D010146
10524660	189	207	migraine with aura	Disease	D020325
10524660	212	233	migraine without aura	Disease	D020326
10524660	352	364	nitric oxide	Chemical	D009569
10524660	366	368	NO	Chemical	D009569
10524660	385	389	pain	Disease	D010146
10524660	404	425	migraine without aura	Disease	D020326
10524660	476	494	migraine with aura	Disease	D020325
10524660	533	541	headache	Disease	D006261
10524660	578	597	glyceryl trinitrate	Chemical	D005996
10524660	599	602	GTN	Chemical	D005996
10524660	654	672	migraine with aura	Disease	D020325
10524660	744	765	migraine without aura	Disease	D020326
10524660	878	886	Headache	Disease	D006261
10524660	906	917	migraineurs	Disease	D008881
10524660	968	971	GTN	Chemical	D005996
10524660	1062	1065	GTN	Chemical	D005996
10524660	1074	1082	headache	Disease	D006261
10524660	1117	1128	migraineurs	Disease	D008881
10524660	1134	1142	headache	Disease	D006261
10524660	1228	1236	headache	Disease	D006261
10524660	1248	1259	migraineurs	Disease	D008881
10524660	1298	1319	migraine without aura	Disease	D020326
10524660	1341	1349	Headache	Disease	D006261
10524660	1394	1396	NO	Chemical	D009569
10524660	1416	1420	pain	Disease	D010146
10524660	1435	1453	migraine with aura	Disease	D020325
10524660	1480	1490	depression	Disease	D003866
10524660	1518	1520	NO	Chemical	D009569
10524660	1616	1626	depression	Disease	D003866
10524660	1631	1639	headache	Disease	D006261
10524660	1643	1661	migraine with aura	Disease	D020325
10524660	CID	D009569	D020326
10524660	CID	D005996	D020326

9799166|t|Stroke and cocaine or amphetamine use.
9799166|a|The association of cocaine and amphetamine use with hemorrhagic and ischemic stroke is based almost solely on data from case series. The limited number of epidemiologic studies of stroke and use of cocaine and/or amphetamine have been done in settings that serve mostly the poor and/or minorities. This case-control study was conducted in the defined population comprising members of Kaiser Permanente of Northern and Southern California. We attempted to identify all incident strokes in women ages 15-44 years during a 3-year period using hospital admission and discharge records, emergency department logs, and payment requests for out-of-plan hospitalizations. We selected controls, matched on age and facility of usual care, at random from healthy members of the health plan. We obtained information in face-to-face interviews. There were 347 confirmed stroke cases and 1,021 controls. The univariate matched odds ratio for stroke in women who admitted to using cocaine and/or amphetamine was 8.5 (95% confidence interval = 3.6-20.0). After further adjustment for potential confounders, the odds ratio in women who reported using cocaine and/or amphetamine was 7.0 (95% confidence interval = 2.8-17.9). The use of cocaine and/or amphetamine is a strong risk factor for stroke in this socioeconomically heterogeneous, insured urban population.
9799166	0	6	Stroke	Disease	D020521
9799166	11	18	cocaine	Chemical	D003042
9799166	22	33	amphetamine	Chemical	D000661
9799166	58	65	cocaine	Chemical	D003042
9799166	70	81	amphetamine	Chemical	D000661
9799166	107	115	ischemic	Disease	D007511
9799166	116	122	stroke	Disease	D020521
9799166	219	225	stroke	Disease	D020521
9799166	237	244	cocaine	Chemical	D003042
9799166	252	263	amphetamine	Chemical	D000661
9799166	516	523	strokes	Disease	D020521
9799166	896	902	stroke	Disease	D020521
9799166	967	973	stroke	Disease	D020521
9799166	1005	1012	cocaine	Chemical	D003042
9799166	1020	1031	amphetamine	Chemical	D000661
9799166	1173	1180	cocaine	Chemical	D003042
9799166	1188	1199	amphetamine	Chemical	D000661
9799166	1257	1264	cocaine	Chemical	D003042
9799166	1272	1283	amphetamine	Chemical	D000661
9799166	1312	1318	stroke	Disease	D020521
9799166	CID	D003042	D020521
9799166	CID	D000661	D020521

9672273|t|Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study.
9672273|a|BACKGROUND: Tamoxifen is a candidate chemopreventive agent in breast cancer, although the drug may be associated with the development of endometrial cancer. Therefore we did a trial in hysterectomised women of tamoxifen as a chemopreventive. METHODS: In October, 1992, we started a double-blind placebo-controlled, randomised trial of tamoxifen in women (mainly in Italy) who did not have breast cancer and who had had a hysterectomy. Women were randomised to receive tamoxifen 20 mg per day or placebo, both orally for 5 years. The original plan was to follow the intervention phase by 5 years' follow-up. In June, 1997, the trialists and the data-monitoring committee decided to end recruitment primarily because of the number of women dropping out of the study. Recruitment ended on July 11, 1997, and the study will continue as planned. The primary endpoints are the occurrence of and deaths from breast cancer. This preliminary interim analysis is based on intention-to-treat. FINDINGS: 5408 women were randomised; participating women have a median follow-up of 46 months for major endpoints. 41 cases of breast cancer occurred so far; there have been no deaths from breast cancer. There is no difference in breast-cancer frequency between the placebo (22 cases) and tamoxifen (19) arms. There is a statistically significant reduction of breast cancer among women receiving tamoxifen who also used hormone-replacement therapy during the trial: among 390 women on such therapy and allocated to placebo, we found eight cases of breast cancer compared with one case among 362 women allocated to tamoxifen. Compared with the placebo group, there was a significantly increased risk of vascular events and hypertriglyceridaemia among women on tamoxifen. INTERPRETATION: Although this preliminary analysis has low power, in this cohort of women at low-to-normal risk of breast cancer, the postulated protective effects of tamoxifen are not yet apparent. Women using hormone-replacement therapy appear to have benefited from use of tamoxifen. There were no deaths from breast cancer recorded in women in the study. It is essential to continue follow-up to quantify the long-term risks and benefits of tamoxifen therapy.
9672273	14	27	breast cancer	Disease	D001943
9672273	33	42	tamoxifen	Chemical	D013629
9672273	136	145	Tamoxifen	Chemical	D013629
9672273	176	185	Tamoxifen	Chemical	D013629
9672273	226	239	breast cancer	Disease	D001943
9672273	301	319	endometrial cancer	Disease	D016889
9672273	374	383	tamoxifen	Chemical	D013629
9672273	499	508	tamoxifen	Chemical	D013629
9672273	553	566	breast cancer	Disease	D001943
9672273	632	641	tamoxifen	Chemical	D013629
9672273	1065	1078	breast cancer	Disease	D001943
9672273	1274	1287	breast cancer	Disease	D001943
9672273	1336	1349	breast cancer	Disease	D001943
9672273	1377	1390	breast-cancer	Disease	D001943
9672273	1436	1445	tamoxifen	Chemical	D013629
9672273	1507	1520	breast cancer	Disease	D001943
9672273	1543	1552	tamoxifen	Chemical	D013629
9672273	1695	1708	breast cancer	Disease	D001943
9672273	1761	1770	tamoxifen	Chemical	D013629
9672273	1849	1864	vascular events	Disease	D014652
9672273	1869	1890	hypertriglyceridaemia	Disease	D015228
9672273	1906	1915	tamoxifen	Chemical	D013629
9672273	2032	2045	breast cancer	Disease	D001943
9672273	2084	2093	tamoxifen	Chemical	D013629
9672273	2193	2202	tamoxifen	Chemical	D013629
9672273	2230	2243	breast cancer	Disease	D001943
9672273	2362	2371	tamoxifen	Chemical	D013629
9672273	CID	D013629	D014652
9672273	CID	D013629	D015228

8854309|t|A measure of pupillary oscillation as a marker of cocaine-induced paranoia.
8854309|a|Cocaine-induced paranoia (CIP) remains an important drug-induced model of idiopathic paranoia for which no psychophysiologic marker has yet emerged. Measures of pupillary oscillation were able to significantly distinguish a group of abstinent crack cocaine abusers endorsing past CIP (n = 32) from another group of crack addicts who denied past CIP (n = 29).
8854309	13	34	pupillary oscillation	Disease	D011681
8854309	50	57	cocaine	Chemical	D003042
8854309	66	74	paranoia	Disease	D010259
8854309	76	83	Cocaine	Chemical	D003042
8854309	92	100	paranoia	Disease	D010259
8854309	102	105	CIP	Disease	D010259
8854309	161	169	paranoia	Disease	D010259
8854309	237	258	pupillary oscillation	Disease	D011681
8854309	319	332	crack cocaine	Chemical	D016578
8854309	356	359	CIP	Disease	D010259
8854309	391	396	crack	Chemical	D016578
8854309	421	424	CIP	Disease	D010259
8854309	CID	D003042	D011681
8854309	CID	D003042	D010259

8473723|t|Seizures induced by combined levomepromazine-fluvoxamine treatment.
8473723|a|We report a case of combined levomepromazine-fluvoxamine treatment-induced seizures. It seems that combined treatment of fluvoxamine with phenothiazines may possess proconvulsive activity.
8473723	0	8	Seizures	Disease	D012640
8473723	29	44	levomepromazine	Chemical	D008728
8473723	45	56	fluvoxamine	Chemical	D016666
8473723	97	112	levomepromazine	Chemical	D008728
8473723	113	124	fluvoxamine	Chemical	D016666
8473723	143	151	seizures	Disease	D012640
8473723	189	200	fluvoxamine	Chemical	D016666
8473723	206	220	phenothiazines	Chemical	D010640
8473723	CID	D016666	D012640
8473723	CID	D008728	D012640

6674249|t|Why may epsilon-aminocaproic acid (EACA) induce myopathy in man? Report of a case and literature review.
6674249|a|A case of necrotizing myopathy due to a short epsilon-aminocaproic acid (EACA) treatment in a 72 year-old patient with subarachnoid haemorrhage (SAH) is described. Pathogenetic hypotheses are discussed.
6674249	8	33	epsilon-aminocaproic acid	Chemical	D015119
6674249	35	39	EACA	Chemical	D015119
6674249	48	56	myopathy	Disease	D009135
6674249	115	135	necrotizing myopathy	Disease	D009336|D009135	necrotizing|myopathy
6674249	151	176	epsilon-aminocaproic acid	Chemical	D015119
6674249	178	182	EACA	Chemical	D015119
6674249	224	248	subarachnoid haemorrhage	Disease	D013345
6674249	250	253	SAH	Disease	D013345
6674249	CID	D015119	D009336
6674249	CID	D015119	D009135

6150641|t|Comparison of the effectiveness of ranitidine and cimetidine in inhibiting acid secretion in patients with gastric hypersecretory states.
6150641|a|The H2-histamine receptor antagonists ranitidine and cimetidine were compared for their abilities to control gastric acid hypersecretion on a short- and long-term basis in 22 patients with gastric acid hypersecretory states. Nineteen patients had Zollinger-Ellison syndrome, one patient had systemic mastocytosis, and two patients had idiopathic hypersecretion. The rates of onset of the action of cimetidine and ranitidine were the same. The actions of both drugs were increased by anticholinergic agents, and there was a close correlation between the daily maintenance dose of each drug needed to control acid secretion. However, ranitidine was threefold more potent than cimetidine both in acute inhibition studies and in the median maintenance dose needed (1.2 g per day for ranitidine and 3.6 g per day for cimetidine). Sixty percent of the males developed breast changes or impotence while taking cimetidine and in all cases these changes disappeared when cimetidine was replaced by ranitidine. Treatment with high doses of cimetidine (one to 60 months; median, 11 months) or ranitidine (two to 31 months; median, 14 months) was not associated with hepatic or hematologic toxicity or alterations of serum gastrin concentrations, but ranitidine therapy was associated with a significantly lower serum creatinine level than seen with cimetidine therapy. The results show that both drugs can adequately inhibit acid secretion in patients with gastric hypersecretory states. Both are safe at high doses, but ranitidine is threefold more potent and does not cause the antiandrogen side effects frequently seen with high doses of cimetidine.
6150641	35	45	ranitidine	Chemical	D011899
6150641	50	60	cimetidine	Chemical	D002927
6150641	145	154	histamine	Chemical	D006632
6150641	176	186	ranitidine	Chemical	D011899
6150641	191	201	cimetidine	Chemical	D002927
6150641	385	411	Zollinger-Ellison syndrome	Disease	D015043
6150641	429	450	systemic mastocytosis	Disease	D034721
6150641	536	546	cimetidine	Chemical	D002927
6150641	551	561	ranitidine	Chemical	D011899
6150641	770	780	ranitidine	Chemical	D011899
6150641	812	822	cimetidine	Chemical	D002927
6150641	917	927	ranitidine	Chemical	D011899
6150641	950	960	cimetidine	Chemical	D002927
6150641	1018	1027	impotence	Disease	D007172
6150641	1041	1051	cimetidine	Chemical	D002927
6150641	1100	1110	cimetidine	Chemical	D002927
6150641	1127	1137	ranitidine	Chemical	D011899
6150641	1168	1178	cimetidine	Chemical	D002927
6150641	1220	1230	ranitidine	Chemical	D011899
6150641	1293	1324	hepatic or hematologic toxicity	Disease	D056486|D006402	hepatic toxicity|hematologic toxicity
6150641	1377	1387	ranitidine	Chemical	D011899
6150641	1444	1454	creatinine	Chemical	D003404
6150641	1476	1486	cimetidine	Chemical	D002927
6150641	1648	1658	ranitidine	Chemical	D011899
6150641	1768	1778	cimetidine	Chemical	D002927
6150641	CID	D002927	D007172

3670965|t|A catch in the Reye.
3670965|a|Twenty-six cases of Reye syndrome from The Children's Hospital, Camperdown, Australia, occurring between 1973 and 1982 were reviewed. Of these, 20 cases met the US Public Health Service Centers for Disease Control criteria for the diagnosis of Reye syndrome. Aspirin or salicylate ingestion had occurred in only one of the 20 cases (5%), and paracetamol (acetaminophen) had been administered in only six of the cases (30%). Pathologic confirmation of the diagnosis of Reye syndrome was accomplished in 90% of the cases. The incidence of Reye syndrome in New South Wales, Australia, is estimated from this study to be approximately nine cases per 1 million children compared with recent US data of ten to 20 cases per 1 million children and three to seven cases per 1 million children in Great Britain. The mortality for these Reye syndrome cases in Australia was 45% as compared with a 32% case-fatality rate in the United States. In Australia, the pediatric usage of aspirin has been extremely low for the past 25 years (less than 1% of total dosage units sold), with paracetamol (acetaminophen) dominating the pediatric analgesic and antipyretic market. Reye syndrome may be disappearing from Australia despite a total lack of association with salicylates or aspirin ingestion, since there were no cases found at The Children's Hospital in 1983, 1984, or 1985.
3670965	15	19	Reye	Disease	D012202
3670965	41	54	Reye syndrome	Disease	D012202
3670965	265	278	Reye syndrome	Disease	D012202
3670965	280	287	Aspirin	Chemical	D001241
3670965	291	301	salicylate	Chemical	D012459
3670965	363	374	paracetamol	Chemical	D000082
3670965	376	389	acetaminophen	Chemical	D000082
3670965	489	502	Reye syndrome	Disease	D012202
3670965	558	571	Reye syndrome	Disease	D012202
3670965	847	860	Reye syndrome	Disease	D012202
3670965	989	996	aspirin	Chemical	D001241
3670965	1090	1101	paracetamol	Chemical	D000082
3670965	1103	1116	acetaminophen	Chemical	D000082
3670965	1177	1190	Reye syndrome	Disease	D012202
3670965	1267	1278	salicylates	Chemical	D012459
3670965	1282	1289	aspirin	Chemical	D001241
3670965	CID	D001241	D012202

3300918|t|St. Anthony's fire, then and now: a case report and historical review.
3300918|a|A rare case of morbid vasospasm, together with striking angiographic findings, is described secondary to the ingestion of methysergide by a 48-year-old woman. A brief review of the literature on similar cases is presented. A discussion of the history of ergot includes its original discovery, the epidemics of gangrene that it has caused through the ages and its past and present role in the management of migraine headache. Despite the advent of calcium channel blockers and beta-adrenergic antagonists, ergot preparations continue to play a major role in migraine therapy, so that the danger of St. Anthony's fire persists.
3300918	0	18	St. Anthony's fire	Disease	D004881
3300918	93	102	vasospasm	Disease	D014652
3300918	193	205	methysergide	Chemical	D008784
3300918	325	330	ergot	Chemical	D004876
3300918	381	389	gangrene	Disease	D005734
3300918	477	494	migraine headache	Disease	D008881
3300918	518	525	calcium	Chemical	D002118
3300918	576	581	ergot	Chemical	D004876
3300918	628	636	migraine	Disease	D008881
3300918	668	686	St. Anthony's fire	Disease	D004881
3300918	CID	D004876	D008881
3300918	CID	D008784	D014652

2826064|t|Beta-2-adrenoceptor-mediated hypokalemia and its abolishment by oxprenolol.
2826064|a|The time course and concentration-effect relationship of terbutaline-induced hypokalemia was studied, using computer-aided pharmacokinetic-dynamic modeling. Subsequently we investigated the efficacy of oxprenolol in antagonizing such hypokalemia, together with the pharmacokinetic interaction between both drugs. Six healthy subjects were given a 0.5 mg subcutaneous dose of terbutaline on two occasions: 1 hour after oral administration of a placebo and 1 hour after 80 mg oxprenolol orally. In the 7-hour period after terbutaline administration, plasma samples were taken for determination of plasma potassium levels and drug concentrations. The sigmoid Emax model offered a good description of the relation between terbutaline concentrations and potassium effects. Oxprenolol caused decreases of 65% and 56% of terbutaline volume of distribution and clearance, respectively, and an increase of 130% of its AUC. In spite of higher terbutaline concentrations after oxprenolol pretreatment, the hypokalemia was almost completely antagonized by the beta 2-blocking action.
2826064	29	40	hypokalemia	Disease	D007008
2826064	64	74	oxprenolol	Chemical	D010096
2826064	133	144	terbutaline	Chemical	D013726
2826064	153	164	hypokalemia	Disease	D007008
2826064	278	288	oxprenolol	Chemical	D010096
2826064	310	321	hypokalemia	Disease	D007008
2826064	451	462	terbutaline	Chemical	D013726
2826064	550	560	oxprenolol	Chemical	D010096
2826064	596	607	terbutaline	Chemical	D013726
2826064	678	687	potassium	Chemical	D011188
2826064	794	805	terbutaline	Chemical	D013726
2826064	825	834	potassium	Chemical	D011188
2826064	844	854	Oxprenolol	Chemical	D010096
2826064	890	901	terbutaline	Chemical	D013726
2826064	1009	1020	terbutaline	Chemical	D013726
2826064	1042	1052	oxprenolol	Chemical	D010096
2826064	1071	1082	hypokalemia	Disease	D007008
2826064	CID	D013726	D007008

2422478|t|Midline B3 serotonin nerves in rat medulla are involved in hypotensive effect of methyldopa.
2422478|a|Previous experiments in this laboratory have shown that microinjection of methyldopa onto the ventrolateral cells of the B3 serotonin neurons in the medulla elicits a hypotensive response mediated by a projection descending into the spinal cord. The present experiments were designed to investigate the role of the midline cells of the B3 serotonin neurons in the medulla, coinciding with the raphe magnus. In spontaneously hypertensive, stroke-prone rats, microinjection of methyldopa into the area of the midline B3 serotonin cell group in the ventral medulla caused a potent hypotension of 30-40 mm Hg, which was maximal 2-3 h after administration and was abolished by the serotonin neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) injected intracerebroventricularly. However, intraspinal injection of 5,7-DHT to produce a more selective lesion of only descending serotonin projections in the spinal cord did not affect this hypotension. Further, 5,7-DHT lesion of serotonin nerves travelling in the median forebrain bundle, one of the main ascending pathways from the B3 serotonin cells, did not affect the fall in blood pressure associated with a midline B3 serotonin methyldopa injection. It is concluded therefore that, unlike the ventrolateral B3 cells which mediate a methyldopa-induced hypotension via descending projections, the midline serotonin B3 cells in the medulla contribute to the hypotensive action of methyldopa, either by way of an ascending projection which does not pass through the median forebrain bundle, or through a projection restricted to the caudal brainstem.
2422478	11	20	serotonin	Chemical	D012701
2422478	59	70	hypotensive	Disease	D007022
2422478	81	91	methyldopa	Chemical	D008750
2422478	167	177	methyldopa	Chemical	D008750
2422478	217	226	serotonin	Chemical	D012701
2422478	260	271	hypotensive	Disease	D007022
2422478	432	441	serotonin	Chemical	D012701
2422478	517	529	hypertensive	Disease	D006973
2422478	531	537	stroke	Disease	D020521
2422478	568	578	methyldopa	Chemical	D008750
2422478	611	620	serotonin	Chemical	D012701
2422478	671	682	hypotension	Disease	D007022
2422478	769	778	serotonin	Chemical	D012701
2422478	790	813	5,7-dihydroxytryptamine	Chemical	D015116
2422478	815	822	5,7-DHT	Chemical	D015116
2422478	894	901	5,7-DHT	Chemical	D015116
2422478	956	965	serotonin	Chemical	D012701
2422478	1017	1028	hypotension	Disease	D007022
2422478	1039	1046	5,7-DHT	Chemical	D015116
2422478	1057	1066	serotonin	Chemical	D012701
2422478	1164	1173	serotonin	Chemical	D012701
2422478	1252	1261	serotonin	Chemical	D012701
2422478	1262	1272	methyldopa	Chemical	D008750
2422478	1366	1376	methyldopa	Chemical	D008750
2422478	1385	1396	hypotension	Disease	D007022
2422478	1437	1446	serotonin	Chemical	D012701
2422478	1489	1500	hypotensive	Disease	D007022
2422478	1511	1521	methyldopa	Chemical	D008750
2422478	CID	D008750	D007022

1535072|t|Yohimbine treatment of sexual side effects induced by serotonin reuptake blockers.
1535072|a|BACKGROUND: Preclinical and clinical studies suggest that yohimbine facilitates sexual behavior and may be helpful in the treatment of male impotence. A single case report suggests that yohimbine may be used to treat the sexual side effects of clomipramine. This study evaluated yohimbine as a treatment for the sexual side effects caused by serotonin reuptake blockers. METHOD: Six patients with either obsessive compulsive disorder, trichotillomania, anxiety, or affective disorders who suffered sexual side effects after treatment with serotonin reuptake blockers were given yohimbine on a p.r.n. basis in an open clinical trial. Various doses of yohimbine were used to determine the ideal dose for each patient. RESULTS: Five of the six patients experienced improved sexual functioning after taking yohimbine. One patient who failed to comply with yohimbine treatment had no therapeutic effects. Side effects of yohimbine included excessive sweating, increased anxiety, and a wound-up feeling in some patients. CONCLUSION: The results of this study indicate that yohimbine may be an effective treatment for the sexual side effects caused by serotonin reuptake blockers. Future controlled studies are needed to further investigate the effectiveness and safety of yohimbine for this indication.
1535072	0	9	Yohimbine	Chemical	D015016
1535072	23	42	sexual side effects	Disease	D020018
1535072	54	63	serotonin	Chemical	D012701
1535072	141	150	yohimbine	Chemical	D015016
1535072	218	232	male impotence	Disease	D007172
1535072	269	278	yohimbine	Chemical	D015016
1535072	304	323	sexual side effects	Disease	D020018
1535072	327	339	clomipramine	Chemical	D002997
1535072	362	371	yohimbine	Chemical	D015016
1535072	395	414	sexual side effects	Disease	D020018
1535072	425	434	serotonin	Chemical	D012701
1535072	487	516	obsessive compulsive disorder	Disease	D009771
1535072	518	534	trichotillomania	Disease	D014256
1535072	536	543	anxiety	Disease	D001008
1535072	548	567	affective disorders	Disease	D019964
1535072	581	600	sexual side effects	Disease	D020018
1535072	622	631	serotonin	Chemical	D012701
1535072	661	670	yohimbine	Chemical	D015016
1535072	733	742	yohimbine	Chemical	D015016
1535072	886	895	yohimbine	Chemical	D015016
1535072	935	944	yohimbine	Chemical	D015016
1535072	999	1008	yohimbine	Chemical	D015016
1535072	1048	1055	anxiety	Disease	D001008
1535072	1150	1159	yohimbine	Chemical	D015016
1535072	1198	1217	sexual side effects	Disease	D020018
1535072	1228	1237	serotonin	Chemical	D012701
1535072	1349	1358	yohimbine	Chemical	D015016
1535072	CID	D002997	D020018

1504402|t|Hypersensitivity immune reaction as a mechanism for dilevalol-associated hepatitis.
1504402|a|OBJECTIVE: To assess lymphocyte reactivity to dilevalol and to serum containing putative ex vivo dilevalol antigens or metabolites in a case of dilevalol-induced liver injury. PATIENT: A 58-year-old woman with a clinical diagnosis of dilevalol-induced liver injury. METHODS: Peripheral blood mononuclear cells collected from the patient were cultured in the presence of a solution of dilevalol and also with sera collected from a volunteer before and after dilevalol intake. A similar protocol was performed with lymphocytes from a healthy subject. RESULTS: No lymphocyte proliferation was observed either in the patient or in the healthy volunteer in the presence of dilevalol solutions. A significant proliferative response to serum collected after dilevalol intake was observed in the case of the patient compared with the proliferative response to the serum collected before the drug intake. No reactivity was found when lymphocytes from the healthy subject were tested under similar conditions. CONCLUSIONS: The methodology used allowed the detection of lymphocyte sensitization to sera containing ex vivo-prepared dilevalol antigens, suggesting the involvement of an immunologic mechanism in dilevalol-induced liver injury.
1504402	0	16	Hypersensitivity	Disease	D004342
1504402	52	61	dilevalol	Chemical	D007741
1504402	73	82	hepatitis	Disease	D056486
1504402	130	139	dilevalol	Chemical	D007741
1504402	181	190	dilevalol	Chemical	D007741
1504402	228	237	dilevalol	Chemical	D007741
1504402	246	258	liver injury	Disease	D056486
1504402	318	327	dilevalol	Chemical	D007741
1504402	336	348	liver injury	Disease	D056486
1504402	468	477	dilevalol	Chemical	D007741
1504402	541	550	dilevalol	Chemical	D007741
1504402	752	761	dilevalol	Chemical	D007741
1504402	835	844	dilevalol	Chemical	D007741
1504402	1204	1213	dilevalol	Chemical	D007741
1504402	1282	1291	dilevalol	Chemical	D007741
1504402	1300	1312	liver injury	Disease	D056486
1504402	CID	D007741	D056486
1504402	CID	D007741	D004342

19917396|t|Reversible myocardial hypertrophy induced by tacrolimus in a pediatric heart transplant recipient: case report.
19917396|a|Tacrolimus is a potent immunosuppressant that is frequently used in organ transplantation. However, adverse effects include cardiac toxicity. Herein we describe transient myocardial hypertrophy induced by tacrolimus after heart transplantation. The hypertrophy caused no clinical symptoms but was noted because of elevation of plasma brain natriuretic peptide concentration and confirmed at echocardiography. Initially, allograft rejection was feared; however, myocardial biopsy samples revealed only interstitial edema and mild myocardial hypertrophy; neither cellular nor humoral rejection was detected. The blood tacrolimus concentration was higher than usual at that time; thus, tacrolimus dosage was reduced. Myocardial hypertrophy completely resolved upon reducing the target concentration of tacrolimus and did not recur, as confirmed at echocardiography and myocardial biopsy. Thus, we conclude that tacrolimus induces reversible myocardial hypertrophy. In patients receiving tacrolimus therapy, blood concentration should be carefully controlled and extreme attention paid to cardiac involvement.
19917396	11	33	myocardial hypertrophy	Disease	D006332
19917396	45	55	tacrolimus	Chemical	D016559
19917396	112	122	Tacrolimus	Chemical	D016559
19917396	236	252	cardiac toxicity	Disease	D066126
19917396	283	305	myocardial hypertrophy	Disease	D006332
19917396	317	327	tacrolimus	Chemical	D016559
19917396	361	372	hypertrophy	Disease	D006984
19917396	626	631	edema	Disease	D004487
19917396	641	663	myocardial hypertrophy	Disease	D006332
19917396	728	738	tacrolimus	Chemical	D016559
19917396	795	805	tacrolimus	Chemical	D016559
19917396	826	848	Myocardial hypertrophy	Disease	D006332
19917396	911	921	tacrolimus	Chemical	D016559
19917396	1020	1030	tacrolimus	Chemical	D016559
19917396	1050	1072	myocardial hypertrophy	Disease	D006332
19917396	1096	1106	tacrolimus	Chemical	D016559
19917396	CID	D016559	D006332

19234905|t|Comparison of unilateral pallidotomy and subthalamotomy findings in advanced idiopathic Parkinson's disease.
19234905|a|A prospective, randomized, double-blind pilot study to compare the results of stereotactic unilateral pallidotomy and subthalamotomy in advanced idiopathic Parkinson's disease (PD) refractory to medical treatment was designed. Ten consecutive patients (mean age, 58.4 +/- 6.8 years; 7 men, 3 women) with similar characteristics at the duration of disease (mean disease time, 8.4 +/- 3.5 years), disabling motor fluctuations (Hoehn _ Yahr stage 3-5 in off-drug phases) and levodopa-induced dyskinesias were selected. All patients had bilateral symptoms and their levodopa equivalent dosing were analysed. Six patients were operated on in the globus pallidus interna (GPi) and four in the subthalamic nucleus (STN). Clinical evaluation included the use of the Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn_Yahr score and Schwab England activities of daily living (ADL) score in 'on'- and 'off'-drug conditions before surgery and 6 months after surgery. There was statistically significant improvement in all contralateral major parkinsonian motor signs in all patients followed for 6 months. Levodopa equivalent daily intake was significantly reduced in the STN group. Changes in UPDRS, Hoehn _ Yahr and Schwab England ADL scores were similar in both groups. Cognitive functions were unchanged in both groups. Complications were observed in two patients: one had a left homonymous hemianopsia after pallidotomy and another one developed left hemiballistic movements 3 days after subthalamotomy which partly improved within 1 month with Valproate 1000 mg/day. The findings of this study suggest that lesions of the unilateral STN and GPi are equally effective treatment for patients with advanced PD refractory to medical treatment.
19234905	77	107	idiopathic Parkinson's disease	Disease	D010300
19234905	254	284	idiopathic Parkinson's disease	Disease	D010300
19234905	286	288	PD	Disease	D010300
19234905	581	589	levodopa	Chemical	D007980
19234905	598	609	dyskinesias	Disease	D004409
19234905	671	679	levodopa	Chemical	D007980
19234905	875	894	Parkinson's Disease	Disease	D010300
19234905	1145	1157	parkinsonian	Disease	D010300
19234905	1209	1217	Levodopa	Chemical	D007980
19234905	1487	1509	homonymous hemianopsia	Disease	D006423
19234905	1653	1662	Valproate	Chemical	D014635
19234905	1813	1815	PD	Disease	D010300
19234905	CID	D007980	D004409

18541230|t|Protective effects of antithrombin on puromycin aminonucleoside nephrosis in rats.
18541230|a|We investigated the effects of antithrombin, a plasma inhibitor of coagulation factors, in rats with puromycin aminonucleoside-induced nephrosis, which is an experimental model of human nephrotic syndrome. Antithrombin (50 or 500 IU/kg/i.v.) was administered to rats once a day for 10 days immediately after the injection of puromycin aminonucleoside (50 mg/kg/i.v.). Treatment with antithrombin attenuated the puromycin aminonucleoside-induced hematological abnormalities. Puromycin aminonucleoside-induced renal dysfunction and hyperlipidemia were also suppressed. Histopathological examination revealed severe renal damage such as proteinaceous casts in tubuli and tubular expansion in the kidney of control rats, while an improvement of the damage was seen in antithrombin-treated rats. In addition, antithrombin treatment markedly suppressed puromycin aminonucleoside-induced apoptosis of renal tubular epithelial cells. Furthermore, puromycin aminonucleoside-induced increases in renal cytokine content were also decreased. These findings suggest that thrombin plays an important role in the pathogenesis of puromycin aminonucleoside-induced nephrotic syndrome. Treatment with antithrombin may be clinically effective in patients with nephrotic syndrome.
18541230	38	63	puromycin aminonucleoside	Chemical	D011692
18541230	64	73	nephrosis	Disease	D009401
18541230	184	209	puromycin aminonucleoside	Chemical	D011692
18541230	218	227	nephrosis	Disease	D009401
18541230	269	287	nephrotic syndrome	Disease	D009404
18541230	408	433	puromycin aminonucleoside	Chemical	D011692
18541230	494	519	puromycin aminonucleoside	Chemical	D011692
18541230	528	555	hematological abnormalities	Disease	D006402
18541230	557	582	Puromycin aminonucleoside	Chemical	D011692
18541230	591	608	renal dysfunction	Disease	D007674
18541230	613	627	hyperlipidemia	Disease	D006949
18541230	696	708	renal damage	Disease	D007674
18541230	930	955	puromycin aminonucleoside	Chemical	D011692
18541230	1022	1047	puromycin aminonucleoside	Chemical	D011692
18541230	1197	1222	puromycin aminonucleoside	Chemical	D011692
18541230	1231	1249	nephrotic syndrome	Disease	D009404
18541230	1324	1342	nephrotic syndrome	Disease	D009404
18541230	CID	D011692	D009401

18177388|t|Reverse or inverted left ventricular apical ballooning syndrome (reverse Takotsubo cardiomyopathy) in a young woman in the setting of amphetamine use.
18177388|a|Transient left ventricular apical ballooning syndrome was first described in Japan as "Takotsubo cardiomyopathy." This syndrome has been identified in many other countries. Many variations of this syndrome have been recently described in the literature. One of the rarest is the reverse type of this syndrome, with hyperdynamic apex and complete akinesia of the base (as opposed to the classic apical ballooning). In this article, we report an interesting case of a young woman who presented with this rare type of reverse apical ballooning syndrome occurring after amphetamine use. This report is followed by review of the literature.
18177388	20	63	left ventricular apical ballooning syndrome	Disease	D054549
18177388	73	97	Takotsubo cardiomyopathy	Disease	D054549
18177388	134	145	amphetamine	Chemical	D000661
18177388	161	204	left ventricular apical ballooning syndrome	Disease	D054549
18177388	238	262	Takotsubo cardiomyopathy	Disease	D054549
18177388	497	505	akinesia	Disease	D004409
18177388	545	562	apical ballooning	Disease	D054549
18177388	674	700	apical ballooning syndrome	Disease	D054549
18177388	717	728	amphetamine	Chemical	D000661
18177388	CID	D000661	D054549

17490864|t|Attenuated disruption of prepulse inhibition by dopaminergic stimulation after maternal deprivation and adolescent corticosterone treatment in rats.
17490864|a|The development of schizophrenia may include an early neurodevelopmental stress component which increases vulnerability to later stressful life events, in combination leading to overt disease. We investigated the effect of an early stress, in the form of maternal deprivation, combined with a later stress, simulated by chronic periadolescent corticosterone treatment, on behaviour in rats. Acute treatment with apomorphine caused disruption of prepulse inhibition (PPI) in controls and in rats that had undergone either maternal deprivation or corticosterone treatment, but was surprisingly absent in rats that had undergone the combined early and late stress. Amphetamine treatment significantly disrupted PPI in both non-deprived groups, but was absent in both maternally deprived groups. The serotonin-1A receptor agonist, 8-OH-DPAT, induced a significant disruption of PPI in all groups. Amphetamine-induced locomotor hyperactivity was similar in all groups. These results show an inhibitory interaction of early stress, caused by maternal deprivation, combined with 'adolescent' stress, simulated by corticosterone treatment, on dopaminergic regulation of PPI. The altered effects of apomorphine and amphetamine could indicate differential changes in dopamine receptor signalling leading to functional desensitisation, or altered modulation of sensory gating in the nucleus accumbens by limbic structures such as the hippocampus.
17490864	115	129	corticosterone	Chemical	D003345
17490864	168	181	schizophrenia	Disease	D012559
17490864	492	506	corticosterone	Chemical	D003345
17490864	561	572	apomorphine	Chemical	D001058
17490864	694	708	corticosterone	Chemical	D003345
17490864	811	822	Amphetamine	Chemical	D000661
17490864	945	954	serotonin	Chemical	D012701
17490864	976	985	8-OH-DPAT	Chemical	D017371
17490864	1042	1053	Amphetamine	Chemical	D000661
17490864	1062	1085	locomotor hyperactivity	Disease	D006948
17490864	1255	1269	corticosterone	Chemical	D003345
17490864	1339	1350	apomorphine	Chemical	D001058
17490864	1355	1366	amphetamine	Chemical	D000661
17490864	1406	1414	dopamine	Chemical	D004298
17490864	CID	D000661	D006948

17490790|t|Peripheral iron dextran induced degeneration of dopaminergic neurons in rat substantia nigra.
17490790|a|Iron accumulation is considered to be involved in the pathogenesis of Parkinson's disease. To demonstrate the relationship between peripheral iron overload and dopaminergic neuron loss in rat substantia nigra (SN), in the present study we used fast cyclic voltammetry, tyrosine hydroxylase (TH) immunohistochemistry, Perls' iron staining, and high performance liquid chromatography-electrochemical detection to study the degeneration of dopaminergic neurons and increased iron content in the SN of iron dextran overloaded animals. The findings showed that peripheral iron dextran overload increased the iron staining positive cells and reduced the number of TH-immunoreactive neurons in the SN. As a result, dopamine release and content, as well as its metabolites contents were decreased in caudate putamen. Even more dramatic changes were found in chronic overload group. These results suggest that peripheral iron dextran can increase the iron level in the SN, where excessive iron causes the degeneration of dopaminergic neurons. The chronic iron overload may be more destructive to dopaminergic neurons than the acute iron overload.
17490790	11	23	iron dextran	Chemical	D007505
17490790	32	68	degeneration of dopaminergic neurons	Disease	D009410
17490790	94	98	Iron	Chemical	D007501
17490790	164	183	Parkinson's disease	Disease	D010300
17490790	236	240	iron	Chemical	D007501
17490790	363	371	tyrosine	Chemical	D014443
17490790	418	422	iron	Chemical	D007501
17490790	515	551	degeneration of dopaminergic neurons	Disease	D009410
17490790	566	570	iron	Chemical	D007501
17490790	592	604	iron dextran	Chemical	D007505
17490790	661	673	iron dextran	Chemical	D007505
17490790	697	701	iron	Chemical	D007501
17490790	802	810	dopamine	Chemical	D004298
17490790	1006	1018	iron dextran	Chemical	D007505
17490790	1036	1040	iron	Chemical	D007501
17490790	1074	1078	iron	Chemical	D007501
17490790	1090	1126	degeneration of dopaminergic neurons	Disease	D009410
17490790	1140	1144	iron	Chemical	D007501
17490790	1217	1221	iron	Chemical	D007501
17490790	CID	D007505	D009410

16047871|t|Warfarin-induced leukocytoclastic vasculitis.
16047871|a|Skin reactions associated with oral coumarin-derived anticoagulants are an uncommon occurrence. Leukocytoclastic vasculitis (LV) is primarily a cutaneous small vessel vasculitis, though systemic involvement may be encountered. We report 4 patients with late-onset LV probably due to warfarin. All 4 patients presented with skin eruptions that developed after receiving warfarin for several years. The results of skin lesion biopsies were available in 3 patients, confirming LV Cutaneous lesions resolved in all patients after warfarin was discontinued. In 2 of the 4 patients, rechallenge with warfarin led to recurrence of the lesions. LV may be a late-onset adverse reaction associated with warfarin therapy.
16047871	0	8	Warfarin	Chemical	D014859
16047871	17	44	leukocytoclastic vasculitis	Disease	C535509
16047871	82	90	coumarin	Chemical	C030123
16047871	142	169	Leukocytoclastic vasculitis	Disease	C535509
16047871	171	173	LV	Disease	C535509
16047871	190	223	cutaneous small vessel vasculitis	Disease	C565222
16047871	310	312	LV	Disease	C535509
16047871	329	337	warfarin	Chemical	D014859
16047871	369	383	skin eruptions	Disease	D012871
16047871	415	423	warfarin	Chemical	D014859
16047871	458	469	skin lesion	Disease	D012871
16047871	520	540	LV Cutaneous lesions	Disease	D018366
16047871	572	580	warfarin	Chemical	D014859
16047871	640	648	warfarin	Chemical	D014859
16047871	683	685	LV	Disease	C535509
16047871	739	747	warfarin	Chemical	D014859
16047871	CID	D014859	D018366

15673851|t|The activation of spinal N-methyl-D-aspartate receptors may contribute to degeneration of spinal motor neurons induced by neuraxial morphine after a noninjurious interval of spinal cord ischemia.
15673851|a|We investigated the relationship between the degeneration of spinal motor neurons and activation of N-methyl-d-aspartate (NMDA) receptors after neuraxial morphine following a noninjurious interval of aortic occlusion in rats. Spinal cord ischemia was induced by aortic occlusion for 6 min with a balloon catheter. In a microdialysis study, 10 muL of saline (group C; n = 8) or 30 mug of morphine (group M; n = 8) was injected intrathecally (IT) 0.5 h after reflow, and 30 mug of morphine (group SM; n = 8) or 10 muL of saline (group SC; n = 8) was injected IT 0.5 h after sham operation. Microdialysis samples were collected preischemia, before IT injection, and at 2, 4, 8, 24, and 48 h of reperfusion (after IT injection). Second, we investigated the effect of IT MK-801 (30 mug) on the histopathologic changes in the spinal cord after morphine-induced spastic paraparesis. After IT morphine, the cerebrospinal fluid (CSF) glutamate concentration was increased in group M relative to both baseline and group C (P < 0.05). This increase persisted for 8 hrs. IT MK-801 significantly reduced the number of dark-stained alpha-motoneurons after morphine-induced spastic paraparesis compared with the saline group. These data indicate that IT morphine induces spastic paraparesis with a concomitant increase in CSF glutamate, which is involved in NMDA receptor activation. We suggest that opioids may be neurotoxic in the setting of spinal cord ischemia via NMDA receptor activation.
15673851	25	45	N-methyl-D-aspartate	Chemical	D016202
15673851	132	140	morphine	Chemical	D009020
15673851	174	194	spinal cord ischemia	Disease	D020760
15673851	296	316	N-methyl-d-aspartate	Chemical	D016202
15673851	318	322	NMDA	Chemical	D016202
15673851	350	358	morphine	Chemical	D009020
15673851	396	412	aortic occlusion	Disease	D001157
15673851	422	442	Spinal cord ischemia	Disease	D020760
15673851	458	474	aortic occlusion	Disease	D001157
15673851	583	591	morphine	Chemical	D009020
15673851	675	683	morphine	Chemical	D009020
15673851	962	968	MK-801	Chemical	D016291
15673851	1034	1042	morphine	Chemical	D009020
15673851	1051	1070	spastic paraparesis	Disease	D020336
15673851	1081	1089	morphine	Chemical	D009020
15673851	1121	1130	glutamate	Chemical	D018698
15673851	1258	1264	MK-801	Chemical	D016291
15673851	1338	1346	morphine	Chemical	D009020
15673851	1355	1374	spastic paraparesis	Disease	D020336
15673851	1435	1443	morphine	Chemical	D009020
15673851	1452	1471	spastic paraparesis	Disease	D020336
15673851	1507	1516	glutamate	Chemical	D018698
15673851	1539	1543	NMDA	Chemical	D016202
15673851	1596	1606	neurotoxic	Disease	D020258
15673851	1625	1645	spinal cord ischemia	Disease	D020760
15673851	1650	1654	NMDA	Chemical	D016202
15673851	CID	D009020	D020336

12481039|t|Reduced sodium channel density, altered voltage dependence of inactivation, and increased susceptibility to seizures in mice lacking sodium channel beta 2-subunits.
12481039|a|Sodium channel beta-subunits modulate channel gating, assembly, and cell surface expression in heterologous cell systems. We generated beta2(-/-) mice to investigate the role of beta2 in control of sodium channel density, localization, and function in neurons in vivo. Measurements of [(3)H]saxitoxin (STX) binding showed a significant reduction in the level of plasma membrane sodium channels in beta2(-/-) neurons. The loss of beta2 resulted in negative shifts in the voltage dependence of inactivation as well as significant decreases in sodium current density in acutely dissociated hippocampal neurons. The integral of the compound action potential in optic nerve was significantly reduced, and the threshold for action potential generation was increased, indicating a reduction in the level of functional plasma membrane sodium channels. In contrast, the conduction velocity, the number and size of axons in the optic nerve, and the specific localization of Na(v)1.6 channels in the nodes of Ranvier were unchanged. beta2(-/-) mice displayed increased susceptibility to seizures, as indicated by reduced latency and threshold for pilocarpine-induced seizures, but seemed normal in other neurological tests. Our observations show that beta2-subunits play an important role in the regulation of sodium channel density and function in neurons in vivo and are required for normal action potential generation and control of excitability.
12481039	8	14	sodium	Chemical	D012964
12481039	108	116	seizures	Disease	D012640
12481039	133	139	sodium	Chemical	D012964
12481039	165	171	Sodium	Chemical	D012964
12481039	363	369	sodium	Chemical	D012964
12481039	456	465	saxitoxin	Chemical	D012530
12481039	467	470	STX	Chemical	D012530
12481039	543	549	sodium	Chemical	D012964
12481039	706	712	sodium	Chemical	D012964
12481039	992	998	sodium	Chemical	D012964
12481039	1129	1131	Na	Chemical	D012964
12481039	1241	1249	seizures	Disease	D012640
12481039	1301	1312	pilocarpine	Chemical	D010862
12481039	1321	1329	seizures	Disease	D012640
12481039	1464	1470	sodium	Chemical	D012964
12481039	CID	D010862	D012640

11185967|t|Screening for stimulant use in adult emergency department seizure patients.
11185967|a|OBJECTIVE: The objective of this study was to determine the prevalence of positive plasma drug screening for cocaine or amphetamine in adult emergency department seizure patients. METHODS: This prospective study evaluated consecutive eligible seizure patients who had a plasma sample collected as part of their clinical evaluation. Plasma was tested for amphetamine and the cocaine metabolite benzoylecgonine using enzyme-mediated immunoassay methodology. Plasma samples with benzoylecgonine greater than 150 ng/mL or an amphetamine greater than 500 ng/mL were defined as positive. Patient demographics, history of underlying drug or alcohol-related seizure disorder, estimated time from seizure to sample collection, history or suspicion of cocaine or amphetamine abuse, results of clinical urine testing for drugs of abuse, and assay results were recorded without patient identifiers. RESULTS: Fourteen of 248 (5.6%, 95% CI 2.7%-8.5%) plasma samples were positive by immunoassay testing for benzoylecgonine and no samples (0%, 95% CI 0-1.2%) were positive for amphetamine. Positive test results were more common in patient visits where there was a history or suspicion of cocaine or amphetamine abuse (p < 0.0005). CONCLUSIONS: During this study period, routine plasma screening for cocaine and amphetamines in adult seizure patients had a low yield. As a result, routine plasma screening would yield few cases of stimulant drug in which there was neither a history nor suspicion of drug abuse in this population.
11185967	58	65	seizure	Disease	D012640
11185967	185	192	cocaine	Chemical	D003042
11185967	196	207	amphetamine	Chemical	D000661
11185967	238	245	seizure	Disease	D012640
11185967	319	326	seizure	Disease	D012640
11185967	430	441	amphetamine	Chemical	D000661
11185967	450	457	cocaine	Chemical	D003042
11185967	469	484	benzoylecgonine	Chemical	C005618
11185967	552	567	benzoylecgonine	Chemical	C005618
11185967	597	608	amphetamine	Chemical	D000661
11185967	710	717	alcohol	Chemical	D000431
11185967	726	733	seizure	Disease	D012640
11185967	764	771	seizure	Disease	D012640
11185967	818	846	cocaine or amphetamine abuse	Disease	D019970|D019969	cocaine abuse|amphetamine abuse
11185967	1069	1084	benzoylecgonine	Chemical	C005618
11185967	1138	1149	amphetamine	Chemical	D000661
11185967	1250	1278	cocaine or amphetamine abuse	Disease	D019970|D019969	cocaine abuse|amphetamine abuse
11185967	1361	1368	cocaine	Chemical	D003042
11185967	1373	1385	amphetamines	Chemical	D000662
11185967	1395	1402	seizure	Disease	D012640
11185967	1561	1571	drug abuse	Disease	D019966
11185967	CID	C005618	D012640

11099450|t|Evidence of functional somatotopy in GPi from results of pallidotomy.
11099450|a|The objective of this study was to explore the functional anatomy of the globus pallidus internus (GPi) by studying the effects of unilateral pallidotomy on parkinsonian 'off' signs and levodopa-induced dyskinesias (LID). We found significant positive correlations between the preoperative levodopa responsiveness of motor signs and the levodopa responsiveness of scores in timed tests (Core Assessment Program for Intracerebral Transplantations) in the contralateral limbs and the improvement in these scores after surgery, whereas there was no correlation with the improvement in LID. We also found a highly significant correlation (P: < 0.0001, r = 0.8) between the volume of the ventral lesion in the GPi and the improvement in LID in the contralateral limbs, whereas there was no correlation between the ventral volume and the improvement in parkinsonian 'off' signs. The volumes of the total lesion cylinder and the dorsal lesion did not correlate with the outcome of either dyskinesias or parkinsonian 'off' signs. The differential predictive value of levodopa responsiveness for the outcome of parkinsonian 'off' signs and LID and the different correlations of ventral lesion volume with dyskinesias and parkinsonian 'off' signs indicate that different anatomical or pathophysiological substrates may be responsible for the generation of parkinsonian 'off' signs and dyskinesias. Whereas cells in a wider area of the GPi may be implicated in parkinsonism, the ventral GPi seems to be crucial for the manifestation of LID. We suggest that our observations are additional proof of the functional somatotopy of the systems within the GPi that mediate parkinsonism and dyskinesias, especially along the dorsoventral trajectory used in pallidotomy. The outcome of pallidotomy in which the lesion involves the ventral and dorsal GPi could be the net effect of alteration in the activity of pathways which mediate different symptoms, and hence could be variable.
11099450	227	239	parkinsonian	Disease	D010300
11099450	256	264	levodopa	Chemical	D007980
11099450	273	284	dyskinesias	Disease	D004409
11099450	286	289	LID	Disease	D004409
11099450	360	368	levodopa	Chemical	D007980
11099450	407	415	levodopa	Chemical	D007980
11099450	652	655	LID	Disease	D004409
11099450	802	805	LID	Disease	D004409
11099450	917	929	parkinsonian	Disease	D010300
11099450	1051	1062	dyskinesias	Disease	D004409
11099450	1066	1078	parkinsonian	Disease	D010300
11099450	1129	1137	levodopa	Chemical	D007980
11099450	1172	1184	parkinsonian	Disease	D010300
11099450	1201	1204	LID	Disease	D004409
11099450	1266	1277	dyskinesias	Disease	D004409
11099450	1282	1294	parkinsonian	Disease	D010300
11099450	1416	1428	parkinsonian	Disease	D010300
11099450	1445	1456	dyskinesias	Disease	D004409
11099450	1520	1532	parkinsonism	Disease	D010300
11099450	1595	1598	LID	Disease	D004409
11099450	1726	1738	parkinsonism	Disease	D010300
11099450	1743	1754	dyskinesias	Disease	D004409
11099450	CID	D007980	D004409

11027904|t|Pain responses in methadone-maintained opioid abusers.
11027904|a|Providing pain management for known opioid abusers is a challenging clinical task, in part because little is known about their pain experience and analgesic requirements. This study was designed to describe pain tolerance and analgesic response in a sample of opioid addicts stabilized in methadone-maintenance (MM) treatment (n = 60) in comparison to matched nondependent control subjects (n = 60). By using a placebo-controlled, two-way factorial design, tolerance to cold-pressor (CP) pain was examined, both before and after oral administration of therapeutic doses of common opioid (hydromorphone 2 mg) and nonsteroidal anti-inflammatory (ketorolac 10 mg) analgesic agents. Results showed that MM individuals were significantly less tolerant of CP pain than control subjects, replicating previous work. Analgesic effects were significant neither for medication nor group. These data indicate that MM opioid abusers represent a pain-intolerant subset of clinical patients. Their complaints of pain should be evaluated seriously and managed aggressively.
11027904	0	4	Pain	Disease	D010146
11027904	18	27	methadone	Chemical	D008691
11027904	65	69	pain	Disease	D010146
11027904	182	186	pain	Disease	D010146
11027904	262	266	pain	Disease	D010146
11027904	315	329	opioid addicts	Disease	D009293
11027904	344	353	methadone	Chemical	D008691
11027904	543	547	pain	Disease	D010146
11027904	643	656	hydromorphone	Chemical	D004091
11027904	699	708	ketorolac	Chemical	D020910
11027904	808	812	pain	Disease	D010146
11027904	987	1002	pain-intolerant	Disease	D006930
11027904	1052	1056	pain	Disease	D010146
11027904	CID	D008691	D006930

10193809|t|Urine N-acetyl-beta-D-glucosaminidase--a marker of tubular damage?
10193809|a|BACKGROUND: Although an indicator of renal tubular dysfunction, an increased urinary N-acetyl-beta-D-glucosaminidase (NAG) activity might reflect increased lysosomal activity in renal tubular cells. METHODS: Puromycin aminonucleoside (PAN) was administered to Sprague Dawley rats to induce proteinuria. Total protein, albumin, NAG activity and protein electrophoretic pattern were assessed in daily urine samples for 33 days. The morphological appearance of the kidneys was examined on days three, four, six, eight and thirty three and the NAG isoenzyme patterns on days zero, four, eight and thirty three. RESULTS: Following intravenous PAN urine volume and urine NAG activity increased significantly by day two, but returned to normal by day four. After day four all treated animals exhibited a marked rise in urine albumin, total protein excretion and NAG activity. Electrophoresis showed a generalised increase in middle and high molecular weight urine proteins from day four onwards. Protein droplets first appeared prominent in tubular cells on day four. Peak urine NAG activity and a change in NAG isoenzyme pattern coincided with both the peak proteinuria and the reduction in intracellular protein and NAG droplets (day six onwards). CONCLUSIONS: This animal model demonstrates that an increase in lysosomal turnover and hence urine NAG activity, occurs when increased protein is presented to the tubular cells. Urine NAG activity is thus a measure of altered function in the renal tubules and not simply an indicator of damage.
10193809	104	129	renal tubular dysfunction	Disease	D005198
10193809	275	300	Puromycin aminonucleoside	Chemical	D011692
10193809	302	305	PAN	Chemical	D011692
10193809	357	368	proteinuria	Disease	D011507
10193809	705	708	PAN	Chemical	D011692
10193809	1219	1230	proteinuria	Disease	D011507
10193809	CID	D011692	D011507

9214597|t|Over expression of vascular endothelial growth factor and its receptor during the development of estrogen-induced rat pituitary tumors may mediate estrogen-initiated tumor angiogenesis.
9214597|a|Estrogens, which have been associated with several types of human and animal cancers, can induce tumor angiogenesis in the pituitary of Fischer 344 rats. The mechanistic details of tumor angiogenesis induction, during estrogen carcinogenesis, are still unknown. To elucidate the role of estrogen in the regulation of tumor angiogenesis in the pituitary of female rats, the density of blood vessels was analysed using factor VIII related antigen (FVIIIRAg) immunohistochemistry and the expression of vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) was examined by Western blot and immunohistochemical analysis. The expression of VEGF receptor (VEGFR-2/Flk-1/KDR) was also examined by immunohistochemistry. The results demonstrated that 17beta-estradiol (E2) induces neovascularization, as well as the growth and enlargement of blood vessels after 7 days of exposure. The high tumor angiogenic potential was associated with an elevated VEGF/VPF protein expression in the E2 exposed pituitary of ovariectomized (OVEX) rats. VEGF/VPF and FVIIIRAg immunohistochemistry and endothelial specific lectin (UEA1) binding studies, indicate that the elevation of VEGF protein expression initially occurred in both blood vessels and non-endothelial cells. After 15 days of E2 exposure, VEGF/VPF protein expression, in the non-endothelial cell population, sharply declined and was restricted to the blood vessels. The function of non-endothelial-derived VEGF is not clear. Furthermore, immunohistochemical studies demonstrated that VEGFR-2 (flk-1/KDR), expression was elevated significantly in the endothelial cells of microblood vessels after 7 days of E2 exposure. These findings suggest that over expression of VEGF and its receptor (VEGFR-2) may play an important role in the initial step of the regulation of estrogen induced tumor angiogenesis in the rat pituitary.
9214597	97	105	estrogen	Chemical	D004967
9214597	118	134	pituitary tumors	Disease	D010911
9214597	147	155	estrogen	Chemical	D004967
9214597	166	171	tumor	Disease	D009369
9214597	186	195	Estrogens	Chemical	D004967
9214597	263	270	cancers	Disease	D009369
9214597	283	288	tumor	Disease	D009369
9214597	367	372	tumor	Disease	D009369
9214597	404	412	estrogen	Chemical	D004967
9214597	413	427	carcinogenesis	Disease	D063646
9214597	473	481	estrogen	Chemical	D004967
9214597	503	508	tumor	Disease	D009369
9214597	948	964	17beta-estradiol	Chemical	D004958
9214597	966	968	E2	Chemical	D004958
9214597	1088	1093	tumor	Disease	D009369
9214597	1182	1184	E2	Chemical	D004958
9214597	1473	1475	E2	Chemical	D004958
9214597	1853	1855	E2	Chemical	D004958
9214597	2013	2021	estrogen	Chemical	D004967
9214597	2030	2035	tumor	Disease	D009369
9214597	CID	D004958	D010911

7604176|t|Pravastatin-associated myopathy. Report of a case.
7604176|a|A case of acute inflammatory myopathy associated with the use of pravastatin, a new hydrophilic 3-hydroxy-3 methylglutaril coenzyme A reductase inhibitor, is reported. The patient, a 69-year-old man was affected by non-insulin-dependent diabetes mellitus and hypertension. He assumed pravastatin (20 mg/day) because of hypercholesterolemia. He was admitted with acute myopathy of the lower limbs which resolved in a few days after pravastatin discontinuation. A previously unknown hypothyroidism, probably due to chronic autoimmune thyroiditis, was evidenced. Muscle biopsy (left gastrocnemius) revealed a perimysial and endomysial inflammatory infiltrate with a prevalence of CD4+ lymphocytes. While lovastatin and simvastatin have been associated with toxic myopathy, pravastatin-associated myopathy could represent a distinct, inflammatory entity.
7604176	0	11	Pravastatin	Chemical	D017035
7604176	23	31	myopathy	Disease	D009135
7604176	67	88	inflammatory myopathy	Disease	D009220
7604176	116	127	pravastatin	Chemical	D017035
7604176	266	305	non-insulin-dependent diabetes mellitus	Disease	D003924
7604176	310	322	hypertension	Disease	D006973
7604176	335	346	pravastatin	Chemical	D017035
7604176	370	390	hypercholesterolemia	Disease	D006937
7604176	419	427	myopathy	Disease	D009135
7604176	482	493	pravastatin	Chemical	D017035
7604176	532	546	hypothyroidism	Disease	D007037
7604176	572	594	autoimmune thyroiditis	Disease	D013967
7604176	752	762	lovastatin	Chemical	D008148
7604176	767	778	simvastatin	Chemical	D019821
7604176	811	819	myopathy	Disease	D009135
7604176	821	832	pravastatin	Chemical	D017035
7604176	844	852	myopathy	Disease	D009135
7604176	CID	D017035	D009220

7282516|t|Dose-effect and structure-function relationships in doxorubicin cardiomyopathy.
7282516|a|The cardiomyopathy (CM) produced by the anticancer drug doxorubicin (DXR) (Adriamycin) provides a unique opportunity to analyze dose-effect and structure-function relationships during development of myocardial disease. We measured the degree of morphologic damage by ultrastructural examination of endomyocardial biopsy and the degree of performance abnormally by right heart catheterization in patients receiving DXR. Morphologic damage was variable but was proportional to the total cumulative DXR dose between 100 and 600 mg/m2. Performance abnormalities correlated weakly with dose, exhibited a curvilinear relationship, and had a "threshold" for expression. Catheterization abnormalities correlated well with morphologic damage (r = 0.57 to 0.78) in a subgroup of patients in whom exercise hemodynamics were measured, and this relationship also exhibited a curvilinear, threshold configuration. In DXR-CM myocardial damage is proportional to the degree of cytotoxic insult (DXR dose) while myocardial function is preserved until a critical dose or degree of damage is reached, after which myocardial performance deteriorates rapidly.
7282516	52	63	doxorubicin	Chemical	D004317
7282516	64	78	cardiomyopathy	Disease	D009202
7282516	84	98	cardiomyopathy	Disease	D009202
7282516	100	102	CM	Disease	D009202
7282516	136	147	doxorubicin	Chemical	D004317
7282516	149	152	DXR	Chemical	D004317
7282516	155	165	Adriamycin	Chemical	D004317
7282516	279	297	myocardial disease	Disease	D009202
7282516	494	497	DXR	Chemical	D004317
7282516	576	579	DXR	Chemical	D004317
7282516	983	986	DXR	Chemical	D004317
7282516	987	989	CM	Disease	D009202
7282516	990	1007	myocardial damage	Disease	D009202
7282516	1059	1062	DXR	Chemical	D004317
7282516	CID	D004317	D009202

7072798|t|Fatal aplastic anemia following topical administration of ophthalmic chloramphenicol.
7072798|a|A 73-year-old woman died of aplastic anemia less than two months after undergoing cataract extraction and beginning topical therapy with chloramphenicol. The first signs of pancytopenia began within one month of the surgery. The pattern of the aplastic anemia was associated with an idiosyncratic response to chloramphenicol. This was the second report of fatal aplastic anemia after topical treatment with chloramphenicol for ocular conditions, although two cases of reversible bone marrow hypoplasia have also been reported. Any other suspected cases of ocular toxicity associated with topically applied chloramphenicol should be reported to the National Registry of Drug-Induced Ocular Side Effects, Oregon Health Sciences University, Portland, OR 97201.
7072798	6	21	aplastic anemia	Disease	D000741
7072798	69	84	chloramphenicol	Chemical	D002701
7072798	114	129	aplastic anemia	Disease	D000741
7072798	168	176	cataract	Disease	D002386
7072798	223	238	chloramphenicol	Chemical	D002701
7072798	259	271	pancytopenia	Disease	D010198
7072798	330	345	aplastic anemia	Disease	D000741
7072798	395	410	chloramphenicol	Chemical	D002701
7072798	448	463	aplastic anemia	Disease	D000741
7072798	493	508	chloramphenicol	Chemical	D002701
7072798	565	587	bone marrow hypoplasia	Disease	D001855
7072798	642	657	ocular toxicity	Disease	D005128
7072798	692	707	chloramphenicol	Chemical	D002701
7072798	CID	D002701	D000741

3769769|t|Bradycardia due to trihexyphenidyl hydrochloride.
3769769|a|A chronic schizophrenic patient was treated with an anticholinergic drug, trihexyphenidyl hydrochloride. The patient developed, paradoxically, sinus bradycardia. The reaction was specific to trihexyphenidyl and not to other anticholinergic drugs. This antidyskinetic drug is widely used in clinical psychiatric practice and physicians should be aware of this side effect.
3769769	0	11	Bradycardia	Disease	D001919
3769769	19	48	trihexyphenidyl hydrochloride	Chemical	D014282
3769769	60	73	schizophrenic	Disease	D012559
3769769	124	153	trihexyphenidyl hydrochloride	Chemical	D014282
3769769	199	210	bradycardia	Disease	D001919
3769769	241	256	trihexyphenidyl	Chemical	D014282
3769769	349	360	psychiatric	Disease	D001523
3769769	CID	D014282	D001919

3708922|t|Experimental cyclosporine nephrotoxicity: risk of concomitant chemotherapy.
3708922|a|The role of cyclosporine (CSA) alone or in combination with various chemotherapeutics in the development of renal toxicity was evaluated in rats. Administration of 20 mg/kg/day CSA for 4 weeks caused renal functional and structural changes similar to those reported in man. The combined administration of CSA and various chemotherapeutic drugs with a nephrotoxic potential, such as gentamicin (at therapeutic doses), amphothericin B and ketoconazole, which are frequently used in immunosuppressed patients, did not aggravate the CSA induced toxicity in the rat model. Gentamicin at toxic doses, however, increased CSA nephrotoxicity. Thus, the nephrotoxicity induced by CSA has a different pathogenetic mechanism.
3708922	13	25	cyclosporine	Chemical	D016572
3708922	26	40	nephrotoxicity	Disease	D007674
3708922	88	100	cyclosporine	Chemical	D016572
3708922	102	105	CSA	Chemical	D016572
3708922	184	198	renal toxicity	Disease	D007674
3708922	253	256	CSA	Chemical	D016572
3708922	381	384	CSA	Chemical	D016572
3708922	427	438	nephrotoxic	Disease	D007674
3708922	458	468	gentamicin	Chemical	D005839
3708922	493	508	amphothericin B	Chemical	D000666
3708922	513	525	ketoconazole	Chemical	D007654
3708922	605	608	CSA	Chemical	D016572
3708922	617	625	toxicity	Disease	D064420
3708922	644	654	Gentamicin	Chemical	D005839
3708922	690	693	CSA	Chemical	D016572
3708922	694	708	nephrotoxicity	Disease	D007674
3708922	720	734	nephrotoxicity	Disease	D007674
3708922	746	749	CSA	Chemical	D016572
3708922	CID	D016572	D007674

3220106|t|Receptor mechanisms of nicotine-induced locomotor hyperactivity in chronic nicotine-treated rats.
3220106|a|Rats were pretreated with saline or nicotine (1.5 mg/kg per day) by subcutaneously implanting each animal with an Alzet osmotic mini-pump which continuously released saline or nicotine for 1, 5 and 14 days. At the end of each pretreatment period, animals were used for (i) determining their locomotor response to acutely injected nicotine (0.2 mg/kg, s.c.) and (ii) measuring the density of L-[3H]nicotine and [3H]spiperone binding sites in the striatum. We observed no changes in nicotine-induced locomotor response, striatal L-[3H]nicotine and [3H]spiperone binding in the animals pretreated with nicotine for 1 day. In rats which were pretreated with nicotine for 5 days, there was a significant increase in the nicotine-stimulated locomotor response which was associated with an increase in the number of L-[3H]nicotine binding sites and also with an elevated dopamine (DA) level in the striatum. The number of striatal [3H]spiperone binding sites was not affected. In animals pretreated with nicotine for 14 days, the nicotine-induced locomotor response remained to be potentiated. However, this response was correlated with an elevated number of striatal [3H]spiperone binding sites, whereas the number of striatal L-[3H]nicotine binding sites and the striatal DA level were normal. These results suggest that chronic nicotine-treated rats develop locomotor hyperactivity in response to nicotine initially due to increases of both the density of nicotinic receptors and DA concentration, followed by inducing DA receptor supersensitivity in the striatum.
3220106	23	31	nicotine	Chemical	D009538
3220106	40	63	locomotor hyperactivity	Disease	D006948
3220106	75	83	nicotine	Chemical	D009538
3220106	134	142	nicotine	Chemical	D009538
3220106	274	282	nicotine	Chemical	D009538
3220106	428	436	nicotine	Chemical	D009538
3220106	495	503	nicotine	Chemical	D009538
3220106	512	521	spiperone	Chemical	D013134
3220106	579	587	nicotine	Chemical	D009538
3220106	631	639	nicotine	Chemical	D009538
3220106	648	657	spiperone	Chemical	D013134
3220106	697	705	nicotine	Chemical	D009538
3220106	752	760	nicotine	Chemical	D009538
3220106	813	821	nicotine	Chemical	D009538
3220106	913	921	nicotine	Chemical	D009538
3220106	962	970	dopamine	Chemical	D004298
3220106	972	974	DA	Chemical	D004298
3220106	1026	1035	spiperone	Chemical	D013134
3220106	1095	1103	nicotine	Chemical	D009538
3220106	1121	1129	nicotine	Chemical	D009538
3220106	1263	1272	spiperone	Chemical	D013134
3220106	1325	1333	nicotine	Chemical	D009538
3220106	1365	1367	DA	Chemical	D004298
3220106	1422	1430	nicotine	Chemical	D009538
3220106	1452	1475	locomotor hyperactivity	Disease	D006948
3220106	1491	1499	nicotine	Chemical	D009538
3220106	1574	1576	DA	Chemical	D004298
3220106	1613	1615	DA	Chemical	D004298
3220106	CID	D009538	D006948

2722224|t|Hydrocortisone-induced hypertension in humans: pressor responsiveness and sympathetic function.
2722224|a|Oral hydrocortisone increases blood pressure and enhances pressor responsiveness in normal human subjects. We studied the effects of 1 week of oral hydrocortisone (200 mg/day) on blood pressure, cardiac output, total peripheral resistance, forearm vascular resistance, and norepinephrine spillover to plasma in eight healthy male volunteers. Although diastolic blood pressure remained unchanged, systolic blood pressure increased from 119 to 135 mm Hg (SED +/- 3.4, p less than 0.01), associated with an increased cardiac output (5.85-7.73 l/min, SED +/- 0.46, p less than 0.01). Total peripheral vascular resistance fell from 15.1 to 12.2 mm Hg/l/min (SED +/- 1.03, p less than 0.05). Resting forearm vascular resistance remained unchanged, but the reflex response to the cold pressor test was accentuated, the rise in resistance increasing from 10.5 mm Hg/ml/100 ml/min (R units) before treatment to 32.6 R units after treatment (SED +/- 6.4, p less than 0.025). The rise in forearm vascular resistance accompanying intra-arterial norepinephrine (25, 50, and 100 ng/min) was also significantly greater after hydrocortisone, increasing from an average of 14.9 +/- 2.4 R units before treatment to 35.1 +/- 5.5 R units after hydrocortisone (SED +/- 6.0, p less than 0.05). A shift to the left in the dose-response relation and fall in threshold suggested increased sensitivity to norepinephrine after treatment. Measurement of resting norepinephrine spillover rate to plasma and norepinephrine uptake indicated that overall resting sympathetic nervous system activity was not increased. The rise in resting blood pressure with hydrocortisone is associated with an increased cardiac output (presumably due to increased blood volume).(ABSTRACT TRUNCATED AT 250 WORDS)
2722224	0	14	Hydrocortisone	Chemical	D006854
2722224	23	35	hypertension	Disease	D006973
2722224	101	115	hydrocortisone	Chemical	D006854
2722224	244	258	hydrocortisone	Chemical	D006854
2722224	369	383	norepinephrine	Chemical	D009638
2722224	600	624	increased cardiac output	Disease	D016534
2722224	1129	1143	norepinephrine	Chemical	D009638
2722224	1206	1220	hydrocortisone	Chemical	D006854
2722224	1320	1334	hydrocortisone	Chemical	D006854
2722224	1475	1489	norepinephrine	Chemical	D009638
2722224	1530	1544	norepinephrine	Chemical	D009638
2722224	1574	1588	norepinephrine	Chemical	D009638
2722224	1686	1716	rise in resting blood pressure	Disease	D006973
2722224	1722	1736	hydrocortisone	Chemical	D006854
2722224	1759	1783	increased cardiac output	Disease	D016534
2722224	CID	D006854	D006973

1636026|t|Effects of suprofen on the isolated perfused rat kidney.
1636026|a|Although suprofen has been associated with the development of acute renal failure in greater than 100 subjects, the mechanism of damage remains unclear. The direct nephrotoxic effects of a single dose of 15 mg of suprofen were compared in the recirculating isolated rat kidney perfused with cell-free buffer with or without the addition of 5 mg/dL of uric acid. There were no significant differences in renal sodium excretion, oxygen consumption, or urinary flow rates in kidneys perfused with suprofen compared with the drug-free control groups. In contrast, a significant decline in glomerular filtration rate was found after the introduction of suprofen to the kidney perfused with uric acid; no changes were found with suprofen in the absence of uric acid. A significant decrease in the baseline excretion rate of uric acid was found in rats given suprofen, compared with drug-free controls. However, the fractional excretion of uric acid was unchanged between the groups over the experimental period. In summary, suprofen causes acute declines in renal function, most likely by directly altering the intrarenal distribution of uric acid.
1636026	11	19	suprofen	Chemical	D013496
1636026	66	74	suprofen	Chemical	D013496
1636026	119	138	acute renal failure	Disease	D058186
1636026	221	232	nephrotoxic	Disease	D007674
1636026	270	278	suprofen	Chemical	D013496
1636026	408	417	uric acid	Chemical	D014527
1636026	466	472	sodium	Chemical	D012964
1636026	484	490	oxygen	Chemical	D010100
1636026	551	559	suprofen	Chemical	D013496
1636026	705	713	suprofen	Chemical	D013496
1636026	742	751	uric acid	Chemical	D014527
1636026	780	788	suprofen	Chemical	D013496
1636026	807	816	uric acid	Chemical	D014527
1636026	875	884	uric acid	Chemical	D014527
1636026	909	917	suprofen	Chemical	D013496
1636026	990	999	uric acid	Chemical	D014527
1636026	1075	1083	suprofen	Chemical	D013496
1636026	1091	1123	acute declines in renal function	Disease	D058186
1636026	1189	1198	uric acid	Chemical	D014527
1636026	CID	D013496	D058186

1610717|t|Cocaine-induced brainstem seizures and behavior.
1610717|a|A variety of abnormal sensory/motor behaviors associated with electrical discharges recorded from the bilateral brainstem were induced in adult WKY rats by mechanical (electrode implants) and DC electrical current stimulations and by acute and chronic administration of cocaine. The electrode implant implicated one side or the other of the reticular system of the brainstem but subjects were not incapacitated by the stimulations. Cocaine (40 mg/kg) was injected subcutaneously for an acute experiment and subsequent 20 mg/kg doses twice daily for 3 days in a chronic study. Cocaine generated more abnormal behaviors in the brainstem perturbation group, especially the electrically perturbated subjects. The abnormal behaviors were yawning, retrocollis, hyperactivity, hypersensitivity, "beating drum" behavior, squealing, head bobbing, circling, sniffing, abnormal posturing, and facial twitching. Shifts in the power frequency spectra of the discharge patterns were noted between quiet and pacing behavioral states. Hypersensitivity to various auditory, tactile, and visual stimulation was present and shifts in the brainstem ambient power spectral frequency occurred in response to tactile stimulation. These findings suggest that the brainstem generates and propagates pathological discharges that can be elicited by mechanical and DC electrical perturbation. Cocaine was found to activate the discharge system and thus induce abnormal behaviors that are generated at the discharge site and at distant sites to which the discharge propagates. Cognitive functions may also be involved since dopaminergic and serotonergic cellular elements at the brainstem level are also implicated.
1610717	0	7	Cocaine	Chemical	D003042
1610717	26	34	seizures	Disease	D012640
1610717	319	326	cocaine	Chemical	D003042
1610717	481	488	Cocaine	Chemical	D003042
1610717	625	632	Cocaine	Chemical	D003042
1610717	804	817	hyperactivity	Disease	D006948
1610717	819	835	hypersensitivity	Disease	D004342
1610717	1068	1084	Hypersensitivity	Disease	D004342
1610717	1414	1421	Cocaine	Chemical	D003042
1610717	CID	D003042	D012640

873132|t|Increased sulfation and decreased 7alpha-hydroxylation of deoxycholic acid in ethinyl estradiol-induced cholestasis in rats.
873132|a|Deoxycholic acid conjugation, transport capacity, and metabolism were compared in control and ethinyl estradiol-treated rats. Control rats were found to have a lower capacity to transport deoxycholic acid than taurodeoxycholic acid, and both were decreased by ethinyl estradiol treatment. During [24-14C]sodium deoxycholate infusion, [14C]biliary bile acid secretion increased, but bile flow did not change significantly in either control or ethinyl estradiol-treated rats. Ethinyl estradiol-treated animals excreted significantly less 14C as taurocholic acid than did control animals, consistent with an impairment of 7alpha-hydroxylation of taurodeoxycholic acid. Ethinyl estradiol treatment did not impair conjugation of deoxycholic acid, but did result in an increase in sulfation of taurodeoxycholic acid from 1.5% in controls to nearly 4.0% (P less than 0.01). These results are consistent with the hypothesis that the rat has a poorer tolerance for deoxycholic acid than do certain other species. Furthermore, the rat converts deoxycholic acid, a poor choleretic, to taurocholic acid, a good choleretic. When this conversion is impaired with ethinyl estradiol treatment, sulfation may be an important alternate pathway for excretion of this potentially harmful bile acid.
873132	58	74	deoxycholic acid	Chemical	D003840
873132	78	95	ethinyl estradiol	Chemical	D004997
873132	104	115	cholestasis	Disease	D002779
873132	125	141	Deoxycholic acid	Chemical	D003840
873132	219	236	ethinyl estradiol	Chemical	D004997
873132	313	329	deoxycholic acid	Chemical	D003840
873132	335	356	taurodeoxycholic acid	Chemical	D013657
873132	385	402	ethinyl estradiol	Chemical	D004997
873132	429	448	sodium deoxycholate	Chemical	D003840
873132	472	481	bile acid	Chemical	D001647
873132	567	584	ethinyl estradiol	Chemical	D004997
873132	599	616	Ethinyl estradiol	Chemical	D004997
873132	668	684	taurocholic acid	Chemical	D013656
873132	768	789	taurodeoxycholic acid	Chemical	D013657
873132	791	808	Ethinyl estradiol	Chemical	D004997
873132	849	865	deoxycholic acid	Chemical	D003840
873132	913	934	taurodeoxycholic acid	Chemical	D013657
873132	1081	1097	deoxycholic acid	Chemical	D003840
873132	1159	1175	deoxycholic acid	Chemical	D003840
873132	1199	1215	taurocholic acid	Chemical	D013656
873132	1274	1291	ethinyl estradiol	Chemical	D004997
873132	1393	1402	bile acid	Chemical	D001647
873132	CID	D004997	D002779

783197|t|Effects of ouabain on myocardial oxygen supply and demand in patients with chronic coronary artery disease. A hemodynamic, volumetric, and metabolic study in patients without heart failure.
783197|a|The effects of digitalis glycosides on myocardial oxygen supply and demand are of particular interest in the presence of obstructive coronary artery disease, but have not been measured previously in man. We assessed the effects of ouabain (0.015 mg/kg body weight) on hemodynamic, volumetric, and metabolic parameters in 11 patients with severe chronic coronary artery disease without clinical congestive heart failure. Because the protocol was long and involved interventions which might affect the determinations, we also studied in nine patients using an identical protocol except that ouabain administration was omitted. Left ventricular end-diastolic pressure and left ventricular end-diastolic volume fell in each patient given ouabain, even though they were initially elevated in only two patients. Left ventricular end-diastolic pressure fell from 11.5+/-1.4 (mean+/-SE) to 5.6+/-0.9 mm Hg (P less than 0.001) and left ventricular end-diastolic volume fell from 100+/-17 to 82+/-12 ml/m2 (P less than 0.01) 1 h after ouabain infusion was completed. The maximum velocity of contractile element shortening increased from 1.68+/-0.11 ml/s to 2.18+/-0.21 muscle-lengths/s (P less than 0.05) and is consistent with an increase in contractility. No significant change in these parameters occurred in the control patients. No significant change in myocardial oxygen consumption occurred after ouabain administration but this may be related to a greater decrease in mean arterial pressure in the ouabain patients than in the control patients. We conclude that in patients with chronic coronary artery disease who are not in clinical congestive heart failure left ventricular end-diastolic volume falls after ouabain administration even when it is initially normal. Though this fall would be associated with a decrease in wall tension, and, therefore, of myocardial oxygen consumption, it may not be of sufficient magnitude to prevent a net increase in myocardial oxygen consumption. Nevertheless, compensatory mechanisms prevent a deterioration of resting myocardial metabolism.
783197	11	18	ouabain	Chemical	D010042
783197	33	39	oxygen	Chemical	D010100
783197	83	106	coronary artery disease	Disease	D003324
783197	175	188	heart failure	Disease	D006333
783197	205	225	digitalis glycosides	Chemical	D004071
783197	240	246	oxygen	Chemical	D010100
783197	323	346	coronary artery disease	Disease	D003324
783197	421	428	ouabain	Chemical	D010042
783197	543	566	coronary artery disease	Disease	D003324
783197	584	608	congestive heart failure	Disease	D006333
783197	779	786	ouabain	Chemical	D010042
783197	924	931	ouabain	Chemical	D010042
783197	1215	1222	ouabain	Chemical	D010042
783197	1550	1556	oxygen	Chemical	D010100
783197	1584	1591	ouabain	Chemical	D010042
783197	1686	1693	ouabain	Chemical	D010042
783197	1775	1798	coronary artery disease	Disease	D003324
783197	1823	1847	congestive heart failure	Disease	D006333
783197	1848	1891	left ventricular end-diastolic volume falls	Disease	D002303
783197	1898	1905	ouabain	Chemical	D010042
783197	2055	2061	oxygen	Chemical	D010100
783197	2153	2159	oxygen	Chemical	D010100
783197	CID	D010042	D002303

9545159|t|Prolongation of the QT interval related to cisapride-diltiazem interaction.
9545159|a|Cisapride, a cytochrome P450 3A4 (CYP3A4) substrate, is widely prescribed for the treatment of gastrointestinal motility disorders. Prolongation of QT interval, torsades de pointes, and sudden cardiac death have been reported after concomitant administration with erythromycin or azole antifungal agents, but not with other CYP3A4 inhibitors. A possible drug interaction occurred in a 45-year-old woman who was taking cisapride for gastroesophageal reflux disorder and diltiazem, an agent that has inhibitory effect on CYP3A4, for hypertension. The patient was in near syncope and had QT-interval prolongation. After discontinuing cisapride, the QT interval returned to normal and symptoms did not recur. We suggest that caution be taken when cisapride is prescribed with any potent inhibitor of CYP3A4, including diltiazem.
9545159	0	31	Prolongation of the QT interval	Disease	D008133
9545159	43	52	cisapride	Chemical	D020117
9545159	53	62	diltiazem	Chemical	D004110
9545159	76	85	Cisapride	Chemical	D020117
9545159	171	206	gastrointestinal motility disorders	Disease	D015835
9545159	208	235	Prolongation of QT interval	Disease	D008133
9545159	237	256	torsades de pointes	Disease	D016171
9545159	262	282	sudden cardiac death	Disease	D016757
9545159	340	352	erythromycin	Chemical	D004917
9545159	356	361	azole	Chemical	D001393
9545159	494	503	cisapride	Chemical	D020117
9545159	508	540	gastroesophageal reflux disorder	Disease	D005764
9545159	545	554	diltiazem	Chemical	D004110
9545159	607	619	hypertension	Disease	D006973
9545159	645	652	syncope	Disease	D013575
9545159	661	685	QT-interval prolongation	Disease	D008133
9545159	707	716	cisapride	Chemical	D020117
9545159	819	828	cisapride	Chemical	D020117
9545159	890	899	diltiazem	Chemical	D004110
9545159	CID	D001393	D016757
9545159	CID	D001393	D008133
9545159	CID	D004110	D008133
9545159	CID	D001393	D016171
9545159	CID	D020117	D016757
9545159	CID	D004917	D016171
9545159	CID	D004917	D008133
9545159	CID	D020117	D008133
9545159	CID	D020117	D016171
9545159	CID	D004917	D016757

8643973|t|Paclitaxel combined with carboplatin in the first-line treatment of advanced ovarian cancer.
8643973|a|In a phase I study to determine the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given as a 3-hour infusion in combination with carboplatin administered every 21 days to women with advanced ovarian cancer, paclitaxel doses were escalated as follows: level 1, 135 mg/m2; level 2, 160 mg/m2; level 3, 185 mg/m2; and level 4,210 mg/m2. The fixed dose of carboplatin at levels 1 through 4 was given to achieve an area under the concentration-time curve (AUC) of 5 using the Calvert formula. In levels 5 and 6 the carboplatin dose was targeted at AUCs of 6 and 7.5, respectively, combined with a fixed paclitaxel dose of 185 mg/m2. To date, 30 previously untreated patients, all with a good performance status (Eastern Cooperative Oncology Group 0 to 2) have been entered into this ongoing study. The dose-limiting toxicity of the combination was myelosuppression (leukopenia, granulocytopenia, and thrombocytopenia). Neurotoxicity was largely moderate. So far, 14 patients are evaluable for response; of these, eight (57%) showed objective (complete or partial) response and disease stabilized in six patients. No patient had disease progression. We conclude that the combination of paclitaxel 185 mg/m2 administered as a 3-hour infusion followed immediately by a 1-hour infusion of carboplatin at an AUC of 6 can be administered safely in a 21-day schedule in the outpatient setting. The recommended dose for phase III studies is paclitaxel 185 mg/m2 and carboplatin AUC 6.
8643973	0	10	Paclitaxel	Chemical	D017239
8643973	25	36	carboplatin	Chemical	D016190
8643973	77	91	ovarian cancer	Disease	D010051
8643973	155	165	paclitaxel	Chemical	D017239
8643973	167	172	Taxol	Chemical	D017239
8643973	266	277	carboplatin	Chemical	D016190
8643973	328	342	ovarian cancer	Disease	D010051
8643973	344	354	paclitaxel	Chemical	D017239
8643973	489	500	carboplatin	Chemical	D016190
8643973	647	658	carboplatin	Chemical	D016190
8643973	735	745	paclitaxel	Chemical	D017239
8643973	948	956	toxicity	Disease	D064420
8643973	980	996	myelosuppression	Disease	D001855
8643973	998	1008	leukopenia	Disease	D007970
8643973	1010	1026	granulocytopenia	Disease	D000380
8643973	1032	1048	thrombocytopenia	Disease	D013921
8643973	1051	1064	Neurotoxicity	Disease	D020258
8643973	1317	1327	paclitaxel	Chemical	D017239
8643973	1417	1428	carboplatin	Chemical	D016190
8643973	1565	1575	paclitaxel	Chemical	D017239
8643973	1590	1601	carboplatin	Chemical	D016190
8643973	CID	D017239	D013921
8643973	CID	D017239	D000380
8643973	CID	D016190	D000380
8643973	CID	D017239	D007970
8643973	CID	D016190	D007970
8643973	CID	D016190	D013921
8643973	CID	D016190	D020258
8643973	CID	D017239	D020258

10743694|t|Treatment of tacrolimus-related adverse effects by conversion to cyclosporine in liver transplant recipients.
10743694|a|When tacrolimus side effects persist despite dose reduction, conversion to cyclosporine-based immunosuppression (CyA) is necessary. We characterized tacrolimus side effects that warranted discontinuation of the drug, and outcomes after conversion. Of 388 liver recipients who received tacrolimus as primary immunosuppression, 70 required conversion to CyA. We recorded indication for conversion, whether conversion was early or late after transplantation, tacrolimus dose and trough blood level at conversion, and incidence of rejection after conversion. Conversion was early in 29 patients (41.4%) and late in 41 (58.6%). Indications for early conversion were neurotoxicity (20), (insulin-dependent) diabetes mellitus (IDDM) (5), nephrotoxicity (3), gastrointestinal (GI) toxicity (6), and cardiomyopathy (1), and for late conversion were neurotoxicity (15), IDDM (12), nephrotoxicity (3), GI toxicity (5), hepatotoxicity (6), post-transplant lmphoproliferate disease (PTLD) (2), cardiomyopathy (1), hemolytic anemia (1), and pruritus (1). All early-conversion patients showed improvement/resolution of symptoms. Among late-conversion patients, 37 (90.2%) had improvement/resolution; in 4 (9.8%), adverse effects persisted. The overall rejection rate was 30%. Sixty-two patients (88.6%) are alive with functioning grafts 686 +/- 362 days (range, 154-1433 days) after conversion. When tacrolimus side effects are unresponsive to dose reduction, conversion to CyA can be accomplished safely, with no increased risk of rejection and excellent long-term outcome.
10743694	13	23	tacrolimus	Chemical	D016559
10743694	65	77	cyclosporine	Chemical	D016572
10743694	115	125	tacrolimus	Chemical	D016559
10743694	185	197	cyclosporine	Chemical	D016572
10743694	259	269	tacrolimus	Chemical	D016559
10743694	395	405	tacrolimus	Chemical	D016559
10743694	566	576	tacrolimus	Chemical	D016559
10743694	771	784	neurotoxicity	Disease	D020258
10743694	791	828	(insulin-dependent) diabetes mellitus	Disease	D003922
10743694	830	834	IDDM	Disease	D003922
10743694	841	855	nephrotoxicity	Disease	D007674
10743694	861	891	gastrointestinal (GI) toxicity	Disease	D005767
10743694	901	915	cardiomyopathy	Disease	D009202
10743694	950	963	neurotoxicity	Disease	D020258
10743694	970	974	IDDM	Disease	D003922
10743694	981	995	nephrotoxicity	Disease	D007674
10743694	1001	1012	GI toxicity	Disease	D005767
10743694	1018	1032	hepatotoxicity	Disease	D056486
10743694	1038	1078	post-transplant lmphoproliferate disease	Disease	D008232
10743694	1080	1084	PTLD	Disease	D008232
10743694	1091	1105	cardiomyopathy	Disease	D009202
10743694	1111	1127	hemolytic anemia	Disease	D000743
10743694	1137	1145	pruritus	Disease	D011537
10743694	1495	1505	tacrolimus	Chemical	D016559
10743694	CID	D016559	D000743
10743694	CID	D016559	D003922
10743694	CID	D016559	D011537
10743694	CID	D016559	D008232
10743694	CID	D016559	D009202
10743694	CID	D016559	D020258
10743694	CID	D016559	D005767
10743694	CID	D016559	D056486
10743694	CID	D016559	D007674

3535719|t|Relative efficacy and toxicity of netilmicin and tobramycin in oncology patients.
3535719|a|We prospectively compared the efficacy and safety of netilmicin sulfate or tobramycin sulfate in conjunction with piperacillin sodium in 118 immunocompromised patients with presumed severe infections. The two treatment regimens were equally efficacious. Nephrotoxicity occurred in a similar proportion in patients treated with netilmicin and tobramycin (17% vs 11%). Ototoxicity occurred in four (9.5%) of 42 netilmicin and piperacillin and in 12 (22%) of 54 tobramycin and piperacillin-treated patients. Of those evaluated with posttherapy audiograms, three of four netilmicin and piperacillin-treated patients had auditory thresholds return to baseline compared with one of nine tobramycin and piperacillin-treated patients. The number of greater than or equal to 15-dB increases in auditory threshold as a proportion of total greater than or equal to 15-dB changes (increases and decreases) was significantly lower in netilmicin and piperacillin- vs tobramycin and piperacillin-treated patients (18 of 78 vs 67 of 115). We conclude that aminoglycoside-associated ototoxicity was less severe and more often reversible with netilmicin than with tobramycin.
3535719	22	30	toxicity	Disease	D064420
3535719	34	44	netilmicin	Chemical	D009428
3535719	49	59	tobramycin	Chemical	D014031
3535719	135	153	netilmicin sulfate	Chemical	D009428
3535719	157	175	tobramycin sulfate	Chemical	D014031
3535719	196	215	piperacillin sodium	Chemical	D010878
3535719	271	281	infections	Disease	D007239
3535719	336	350	Nephrotoxicity	Disease	D007674
3535719	409	419	netilmicin	Chemical	D009428
3535719	424	434	tobramycin	Chemical	D014031
3535719	449	460	Ototoxicity	Disease	D006311
3535719	491	501	netilmicin	Chemical	D009428
3535719	506	518	piperacillin	Chemical	D010878
3535719	541	551	tobramycin	Chemical	D014031
3535719	556	568	piperacillin	Chemical	D010878
3535719	649	659	netilmicin	Chemical	D009428
3535719	664	676	piperacillin	Chemical	D010878
3535719	763	773	tobramycin	Chemical	D014031
3535719	778	790	piperacillin	Chemical	D010878
3535719	1003	1013	netilmicin	Chemical	D009428
3535719	1018	1030	piperacillin	Chemical	D010878
3535719	1035	1045	tobramycin	Chemical	D014031
3535719	1050	1062	piperacillin	Chemical	D010878
3535719	1122	1136	aminoglycoside	Chemical	D000617
3535719	1148	1159	ototoxicity	Disease	D006311
3535719	1207	1217	netilmicin	Chemical	D009428
3535719	1228	1238	tobramycin	Chemical	D014031
3535719	CID	D014031	D006311
3535719	CID	D009428	D006311
3535719	CID	D009428	D007674
3535719	CID	D010878	D006311
3535719	CID	D010878	D007674
3535719	CID	D014031	D007674

6433367|t|Effect of prostaglandin synthetase inhibitors on experimentally induced convulsions in rats.
6433367|a|To investigate the relationship of prostaglandins (PGs) to seizure induction, the effects of six PG synthetase inhibitors on convulsions induced by flurothyl, picrotoxin, pentetrazol (PTZ), electroshock or bicuculline were evaluated. Ibuprofen, sulindac, mefenamic acid, and low dose meclofenamic acid increased the latency-to-onset in the flurothyl and/or PTZ models; the electroshock, picrotoxin and bicuculline models were not significantly affected by any of the pretreatment agents. These results suggest that PGs are involved in the mechanism(s) underlying fluorthyl- and PTZ-induced convulsions, but not picrotoxin-, electroshock-, or bicuculline-induced convulsions.
6433367	10	23	prostaglandin	Chemical	D011453
6433367	72	83	convulsions	Disease	D012640
6433367	128	142	prostaglandins	Chemical	D011453
6433367	144	147	PGs	Chemical	D011453
6433367	152	159	seizure	Disease	D012640
6433367	218	229	convulsions	Disease	D012640
6433367	241	250	flurothyl	Chemical	D005481
6433367	252	262	picrotoxin	Chemical	D010852
6433367	264	275	pentetrazol	Chemical	D010433
6433367	277	280	PTZ	Chemical	D010433
6433367	299	310	bicuculline	Chemical	D001640
6433367	327	336	Ibuprofen	Chemical	D007052
6433367	338	346	sulindac	Chemical	D013467
6433367	348	362	mefenamic acid	Chemical	D008528
6433367	377	394	meclofenamic acid	Chemical	D008469
6433367	433	442	flurothyl	Chemical	D005481
6433367	450	453	PTZ	Chemical	D010433
6433367	480	490	picrotoxin	Chemical	D010852
6433367	495	506	bicuculline	Chemical	D001640
6433367	608	611	PGs	Chemical	D011453
6433367	656	665	fluorthyl	Chemical	D005481
6433367	671	674	PTZ	Chemical	D010433
6433367	683	694	convulsions	Disease	D012640
6433367	704	714	picrotoxin	Chemical	D010852
6433367	735	746	bicuculline	Chemical	D001640
6433367	755	766	convulsions	Disease	D012640
6433367	CID	D005481	D012640
6433367	CID	D001640	D012640
6433367	CID	D010433	D012640
6433367	CID	D010852	D012640

17285209|t|Angiotensin-converting enzyme (ACE) inhibitor-associated angioedema of the stomach and small intestine: a case report.
17285209|a|This is a case report on a 45-year old African-American female with newly diagnosed hypertension, who was started on a combination pill of amlodipine/benazapril 10/5 mg. The very next day, she presented at the emergency room (ER) with abdominal pain, nausea and vomiting. Physical exam, complete metabolic panel, and hemogram were in the normal range. She was discharged from the ER after a few hours of treatment with fluid and analgesics. However, she returned to the ER the next day with the same complaints. This time the physical exam was significant for a distended abdomen with dullness to percussion. CT scan of the abdomen revealed markedly thickened antrum of the stomach, duodenum and jejunum, along with fluid in the abdominal and pelvic cavity. Angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema was suspected, and anti-hypertensive medications were discontinued. Her symptoms improved within the next 24 hours, and repeat CT after 72 hours revealed marked improvement in stomach and small bowel thickening and resolution of ascites. The recognition of angiotensin-converting enzyme (ACE) and angiotensin receptor blocker (ARB) intestinal angioedema constitutes a challenge to primary care physicians, internists, emergency room personal and surgeons.
17285209	57	67	angioedema	Disease	D000799
17285209	203	215	hypertension	Disease	D006973
17285209	258	268	amlodipine	Chemical	D017311
17285209	269	279	benazapril	Chemical	C044946
17285209	354	368	abdominal pain	Disease	D015746
17285209	370	376	nausea	Disease	D009325
17285209	381	389	vomiting	Disease	D014839
17285209	932	942	angioedema	Disease	D000799
17285209	967	979	hypertensive	Disease	D006973
17285209	1172	1179	ascites	Disease	D001201
17285209	1200	1211	angiotensin	Chemical	D000809
17285209	1240	1251	angiotensin	Chemical	D000809
17285209	1275	1296	intestinal angioedema	Disease	D007410|D000799	intestinal|angioedema
17285209	CID	C044946	D000799
17285209	CID	D017311	D000799
17285209	CID	C044946	D007410
17285209	CID	D017311	D007410

15858223|t|Valproic acid I: time course of lipid peroxidation biomarkers, liver toxicity, and valproic acid metabolite levels in rats.
15858223|a|A single dose of valproic acid (VPA), which is a widely used antiepileptic drug, is associated with oxidative stress in rats, as recently demonstrated by elevated levels of 15-F(2t)-isoprostane (15-F(2t)-IsoP). To determine whether there was a temporal relationship between VPA-associated oxidative stress and hepatotoxicity, adult male Sprague-Dawley rats were treated ip with VPA (500 mg/kg) or 0.9% saline (vehicle) once daily for 2, 4, 7, 10, or 14 days. Oxidative stress was assessed by determining plasma and liver levels of 15-F(2t)-IsoP, lipid hydroperoxides (LPO), and thiobarbituric acid reactive substances (TBARs). Plasma and liver 15-F(2t)-IsoP were elevated and reached a plateau after day 2 of VPA treatment compared to control. Liver LPO levels were not elevated until day 7 of treatment (1.8-fold versus control, p < 0.05). Liver and plasma TBARs were not increased until 14 days (2-fold vs. control, p < 0.05). Liver toxicity was evaluated based on serum levels of alpha-glutathione S-transferase (alpha-GST) and by histology. Serum alpha-GST levels were significantly elevated by day 4, which corresponded to hepatotoxicity as shown by the increasing incidence of inflammation of the liver capsule, necrosis, and steatosis throughout the study. The liver levels of beta-oxidation metabolites of VPA were decreased by day 14, while the levels of 4-ene-VPA and (E)-2,4-diene-VPA were not elevated throughout the study. Overall, these findings indicate that VPA treatment results in oxidative stress, as measured by levels of 15-F(2t)-IsoP, which precedes the onset of necrosis, steatosis, and elevated levels of serum alpha-GST.
15858223	0	13	Valproic acid	Chemical	D014635
15858223	63	77	liver toxicity	Disease	D056486
15858223	83	96	valproic acid	Chemical	D014635
15858223	141	154	valproic acid	Chemical	D014635
15858223	156	159	VPA	Chemical	D014635
15858223	297	317	15-F(2t)-isoprostane	Chemical	C075750
15858223	319	332	15-F(2t)-IsoP	Chemical	C075750
15858223	398	401	VPA	Chemical	D014635
15858223	434	448	hepatotoxicity	Disease	D056486
15858223	502	505	VPA	Chemical	D014635
15858223	655	668	15-F(2t)-IsoP	Chemical	C075750
15858223	670	690	lipid hydroperoxides	Chemical	D008054
15858223	692	695	LPO	Chemical	D008054
15858223	702	741	thiobarbituric acid reactive substances	Chemical	D017392
15858223	743	748	TBARs	Chemical	D017392
15858223	768	781	15-F(2t)-IsoP	Chemical	C075750
15858223	833	836	VPA	Chemical	D014635
15858223	874	877	LPO	Chemical	D008054
15858223	982	987	TBARs	Chemical	D017392
15858223	1053	1067	Liver toxicity	Disease	D056486
15858223	1113	1124	glutathione	Chemical	D005978
15858223	1252	1266	hepatotoxicity	Disease	D056486
15858223	1307	1319	inflammation	Disease	D007249
15858223	1342	1350	necrosis	Disease	D009336
15858223	1356	1365	steatosis	Disease	D005234
15858223	1438	1441	VPA	Chemical	D014635
15858223	1488	1497	4-ene-VPA	Chemical	C045022
15858223	1506	1519	2,4-diene-VPA	Chemical	C556631
15858223	1598	1601	VPA	Chemical	D014635
15858223	1666	1679	15-F(2t)-IsoP	Chemical	C075750
15858223	1709	1717	necrosis	Disease	D009336
15858223	1719	1728	steatosis	Disease	D005234
15858223	CID	D017392	D056486
15858223	CID	D014635	D005234
15858223	CID	D014635	D009336
15858223	CID	C075750	D056486
15858223	CID	D014635	D056486
15858223	CID	D008054	D056486

15811908|t|Pheochromocytoma unmasked by amisulpride and tiapride.
15811908|a|OBJECTIVE: To describe the unmasking of pheochromocytoma in a patient treated with amisulpride and tiapride. CASE SUMMARY: A 42-year-old white man developed acute hypertension with severe headache and vomiting 2 hours after the first doses of amisulpride 100 mg and tiapride 100 mg. Both drugs were immediately discontinued, and the patient recovered after subsequent nicardipine and verapamil treatment. Abdominal ultrasound showed an adrenal mass, and postoperative histologic examination confirmed the diagnosis of pheochromocytoma. DISCUSSION: Drug-induced symptoms of pheochromocytoma are often associated with the use of substituted benzamide drugs, but the underlying mechanism is unknown. In our case, use of the Naranjo probability scale indicated a possible relationship between the hypertensive crisis and amisulpride and tiapride therapy. CONCLUSIONS: As of March 24, 2005, this is the first reported case of amisulpride- and tiapride-induced hypertensive crisis in a patient with pheochromocytoma. Physicians and other healthcare professionals should be aware of this potential adverse effect of tiapride and amisulpride.
15811908	0	16	Pheochromocytoma	Disease	D010673
15811908	29	40	amisulpride	Chemical	C012052
15811908	45	53	tiapride	Chemical	D063325
15811908	95	111	pheochromocytoma	Disease	D010673
15811908	138	149	amisulpride	Chemical	C012052
15811908	154	162	tiapride	Chemical	D063325
15811908	218	230	hypertension	Disease	D006973
15811908	243	251	headache	Disease	D006261
15811908	256	264	vomiting	Disease	D014839
15811908	298	309	amisulpride	Chemical	C012052
15811908	321	329	tiapride	Chemical	D063325
15811908	423	434	nicardipine	Chemical	D009529
15811908	439	448	verapamil	Chemical	D014700
15811908	573	589	pheochromocytoma	Disease	D010673
15811908	628	644	pheochromocytoma	Disease	D010673
15811908	694	703	benzamide	Chemical	C037689
15811908	848	860	hypertensive	Disease	D006973
15811908	872	883	amisulpride	Chemical	C012052
15811908	888	896	tiapride	Chemical	D063325
15811908	976	987	amisulpride	Chemical	C012052
15811908	993	1001	tiapride	Chemical	D063325
15811908	1010	1022	hypertensive	Disease	D006973
15811908	1048	1064	pheochromocytoma	Disease	D010673
15811908	1164	1172	tiapride	Chemical	D063325
15811908	1177	1188	amisulpride	Chemical	C012052
15811908	CID	C012052	D006973
15811908	CID	C012052	D014839
15811908	CID	C012052	D006261
15811908	CID	D063325	D014839
15811908	CID	D063325	D006261
15811908	CID	D063325	D006973

15764424|t|Quantitative drug levels in stimulant psychosis: relationship to symptom severity, catecholamines and hyperkinesia.
15764424|a|To examine the relationship between quantitative stimulant drug levels, catecholamines, and psychotic symptoms, nineteen patients in a psychiatric emergency service with a diagnosis of amphetamine- or cocaine-induced psychosis were interviewed, and plasma and urine were collected for quantitative assays of stimulant drug and catecholamine metabolite levels. Methamphetamine or amphetamine levels were related to several psychopathology scores and the global hyperkinesia rating. HVA levels were related to global hyperkinesia but not to psychopathology ratings. Although many other factors such as sensitization may play a role, intensity of stimulant-induced psychotic symptoms and stereotypies appears to be at least in part dose-related.
15764424	38	47	psychosis	Disease	D011605
15764424	83	97	catecholamines	Chemical	D002395
15764424	102	114	hyperkinesia	Disease	D006948
15764424	188	202	catecholamines	Chemical	D002395
15764424	208	226	psychotic symptoms	Disease	D011605
15764424	251	262	psychiatric	Disease	D001523
15764424	301	312	amphetamine	Chemical	D000661
15764424	317	324	cocaine	Chemical	D003042
15764424	333	342	psychosis	Disease	D011605
15764424	443	456	catecholamine	Chemical	D002395
15764424	476	491	Methamphetamine	Chemical	D008694
15764424	495	506	amphetamine	Chemical	D000661
15764424	576	588	hyperkinesia	Disease	D006948
15764424	631	643	hyperkinesia	Disease	D006948
15764424	778	796	psychotic symptoms	Disease	D011605
15764424	801	813	stereotypies	Disease	D019956
15764424	CID	D000661	D006948
15764424	CID	D003042	D006948
15764424	CID	D008694	D011605
15764424	CID	D003042	D011605
15764424	CID	D008694	D006948
15764424	CID	D000661	D011605

12101159|t|Delayed asystolic cardiac arrest after diltiazem overdose; resuscitation with high dose intravenous calcium.
12101159|a|A 51 year old man took a mixed overdose including 1.8-3.6 g of diltiazem, paracetamol, aspirin, isosorbide nitrate, and alcohol. He initially presented to hospital after six hours with mild hypotension and was treated with activated charcoal and intravenous fluids. Eighteen hours after the overdose he had two generalised tonic-clonic seizures. The patient remained unresponsive with junctional bradycardia, unrecordable blood pressure, and then became asystolic. He was resuscitated with high dose (13.5 g) intravenous calcium and adrenaline (epinephrine). He required inotropic support and temporary pacing over the next 48 hours. This case suggests there is a role for aggressive high dose intravenous calcium therapy in severe diltiazem overdose, particularly with the onset of asystole. It should be considered early in cases of cardiac arrest after diltiazem overdose. The case also highlights the problems with delayed toxicity when whole bowel irrigation is not administered.
12101159	8	17	asystolic	Disease	D006323
12101159	18	32	cardiac arrest	Disease	D006323
12101159	39	48	diltiazem	Chemical	D004110
12101159	49	57	overdose	Disease	D062787
12101159	100	107	calcium	Chemical	D002118
12101159	140	148	overdose	Disease	D062787
12101159	172	181	diltiazem	Chemical	D004110
12101159	183	194	paracetamol	Chemical	D000082
12101159	196	203	aspirin	Chemical	D001241
12101159	205	215	isosorbide	Chemical	D007547
12101159	216	223	nitrate	Chemical	D009566
12101159	229	236	alcohol	Chemical	D000431
12101159	299	310	hypotension	Disease	D007022
12101159	400	408	overdose	Disease	D062787
12101159	432	453	tonic-clonic seizures	Disease	D004830
12101159	505	516	bradycardia	Disease	D001919
12101159	563	572	asystolic	Disease	D006323
12101159	630	637	calcium	Chemical	D002118
12101159	642	652	adrenaline	Chemical	D004837
12101159	654	665	epinephrine	Chemical	D004837
12101159	815	822	calcium	Chemical	D002118
12101159	841	850	diltiazem	Chemical	D004110
12101159	851	859	overdose	Disease	D062787
12101159	892	900	asystole	Disease	D006323
12101159	944	958	cardiac arrest	Disease	D006323
12101159	965	974	diltiazem	Chemical	D004110
12101159	975	983	overdose	Disease	D062787
12101159	1036	1044	toxicity	Disease	D064420
12101159	CID	D004110	D062787
12101159	CID	D004110	D007022
12101159	CID	D004110	D006323
12101159	CID	D004110	D001919

6699841|t|Renal papillary necrosis due to naproxen.
6699841|a|A 31-year-old man with rheumatoid arthritis, who had previously been treated with sulindac, fenoprofen calcium, high dose salicylates and gold salts, developed renal papillary necrosis (RPN) 4 months after institution of naproxen therapy. No other factor predisposing to RPN could be discovered. Sulindac was substituted for naproxen and no further adverse renal effects occurred over the next 12 months. We review previous reports linking RPN to antiinflammatory drug use and discuss possible advantages of sulindac in patients who have experienced renal toxicity from other antiinflammatory agents.
6699841	0	24	Renal papillary necrosis	Disease	D007681
6699841	32	40	naproxen	Chemical	D009288
6699841	65	85	rheumatoid arthritis	Disease	D001172
6699841	124	132	sulindac	Chemical	D013467
6699841	134	152	fenoprofen calcium	Chemical	D005279
6699841	164	175	salicylates	Chemical	D012459
6699841	180	184	gold	Chemical	D006046
6699841	202	226	renal papillary necrosis	Disease	D007681
6699841	228	231	RPN	Disease	D007681
6699841	263	271	naproxen	Chemical	D009288
6699841	313	316	RPN	Disease	D007681
6699841	338	346	Sulindac	Chemical	D013467
6699841	367	375	naproxen	Chemical	D009288
6699841	482	485	RPN	Disease	D007681
6699841	550	558	sulindac	Chemical	D013467
6699841	592	606	renal toxicity	Disease	D007674
6699841	CID	D009288	D007681

6127992|t|Adverse interaction between beta-adrenergic blocking drugs and verapamil--report of three cases.
6127992|a|Three patients with ischaemic heart disease developed profound cardiac failure, hypotension and bradycardia during combined therapy with verapamil and beta-adrenergic blocking drugs. This clinical picture resolved completely with cessation of the combined therapy. Baseline left ventricular function, assessed by cardiac catheterisation or nuclear angiography, was normal in two patients and only mildly reduced in the other. Simultaneously administration of beta-adrenergic blocking drugs and verapamil may result in profound adverse interactions and should only be administered with great caution.
6127992	28	58	beta-adrenergic blocking drugs	Chemical	D000319
6127992	63	72	verapamil	Chemical	D014700
6127992	117	140	ischaemic heart disease	Disease	D017202
6127992	160	175	cardiac failure	Disease	D006333
6127992	177	188	hypotension	Disease	D007022
6127992	193	204	bradycardia	Disease	D001919
6127992	234	243	verapamil	Chemical	D014700
6127992	248	278	beta-adrenergic blocking drugs	Chemical	D000319
6127992	556	586	beta-adrenergic blocking drugs	Chemical	D000319
6127992	591	600	verapamil	Chemical	D014700
6127992	CID	D014700	D007022
6127992	CID	D000319	D006333
6127992	CID	D014700	D001919
6127992	CID	D014700	D006333
6127992	CID	D000319	D007022
6127992	CID	D000319	D001919

6115999|t|Adverse reactions to bendrofluazide and propranolol for the treatment of mild hypertension. Report of Medical Research Council Working Party on Mild to Moderate Hypertension.
6115999|a|Participants in the Medical Research Council treatment trial for mild hypertension are randomly allocated to one of four treatment groups: bendrofluazide, propranolol, or a placebo for either of these drugs. The trial is single-blind. 23 582 patient-years of observation have been completed so far, 10 684 on active drugs and 12 898 on placebos. The results show an association between bendrofluazide treatment and impotence, and impotence also occurred more frequently in patients taking propranolol than in those taking placebos. Other adverse reactions significantly linked with active drugs include impaired glucose tolerance in men and women and gout in men, associated with bendrofluazide treatment, and Raynaud's phenomenon and dyspnoea in men and women taking propranolol. No corneal disease is known to have occurred in the propranolol group. Mean serum potassium level fell, and urea and uric acid levels rose, in men and women taking bendrofluazide. In the propranolol group, serum potassium and uric acid levels rose in both sexes, but the urea level rose significantly in women only.
6115999	21	35	bendrofluazide	Chemical	D001539
6115999	40	51	propranolol	Chemical	D011433
6115999	78	90	hypertension	Disease	D006973
6115999	161	173	Hypertension	Disease	D006973
6115999	245	257	hypertension	Disease	D006973
6115999	314	328	bendrofluazide	Chemical	D001539
6115999	330	341	propranolol	Chemical	D011433
6115999	561	575	bendrofluazide	Chemical	D001539
6115999	590	599	impotence	Disease	D007172
6115999	605	614	impotence	Disease	D007172
6115999	664	675	propranolol	Chemical	D011433
6115999	778	804	impaired glucose tolerance	Disease	D018149
6115999	826	830	gout	Disease	D006073
6115999	855	869	bendrofluazide	Chemical	D001539
6115999	885	905	Raynaud's phenomenon	Disease	D011928
6115999	910	918	dyspnoea	Disease	D004417
6115999	943	954	propranolol	Chemical	D011433
6115999	959	974	corneal disease	Disease	D003316
6115999	1008	1019	propranolol	Chemical	D011433
6115999	1038	1047	potassium	Chemical	D011188
6115999	1064	1068	urea	Chemical	D014508
6115999	1073	1082	uric acid	Chemical	D014527
6115999	1120	1134	bendrofluazide	Chemical	D001539
6115999	1143	1154	propranolol	Chemical	D011433
6115999	1168	1177	potassium	Chemical	D011188
6115999	1182	1191	uric acid	Chemical	D014527
6115999	1227	1231	urea	Chemical	D014508
6115999	CID	D001539	D007172
6115999	CID	D011433	D011928
6115999	CID	D001539	D018149
6115999	CID	D001539	D006073
6115999	CID	D011433	D007172
6115999	CID	D011433	D004417

18086064|t|Dexmedetomidine and cardiac protection for non-cardiac surgery: a meta-analysis of randomised controlled trials.
18086064|a|We conducted a systematic review of the effects of dexmedetomidine on cardiac outcomes following non-cardiac surgery. We included prospective, randomised peri-operative studies of dexmedetomidine that reported mortality, cardiac morbidity or adverse drug events. A PubMed Central and EMBASE search was conducted up to July 2007. The reference lists of identified papers were examined for further trials. Of 425 studies identified, 20 were included in the meta-analysis (840 patients). Dexmedetomidine was associated with a trend towards improved cardiac outcomes; all-cause mortality (OR 0.27, 95% CI 0.01-7.13, p = 0.44), non-fatal myocardial infarction (OR 0.26, 95% CI 0.04-1.60, p = 0.14), and myocardial ischaemia (OR 0.65, 95% CI 0.26-1.63, p = 0.36). Peri-operative hypotension (26%, OR 3.80, 95% CI 1.91-7.54, p = 0.0001) and bradycardia (17%, OR 5.45, 95% CI 2.98-9.95, p < 0.00001) were significantly increased. An anticholinergic did not reduce the incidence of bradycardia (p = 0.43). A randomised placebo-controlled trial of dexmedetomidine is warranted.
18086064	0	15	Dexmedetomidine	Chemical	D020927
18086064	164	179	dexmedetomidine	Chemical	D020927
18086064	293	308	dexmedetomidine	Chemical	D020927
18086064	598	613	Dexmedetomidine	Chemical	D020927
18086064	746	767	myocardial infarction	Disease	D009203
18086064	811	831	myocardial ischaemia	Disease	D017202
18086064	886	897	hypotension	Disease	D007022
18086064	947	958	bradycardia	Disease	D001919
18086064	1086	1097	bradycardia	Disease	D001919
18086064	1151	1166	dexmedetomidine	Chemical	D020927
18086064	CID	D020927	D001919
18086064	CID	D020927	D007022

12739036|t|Differential diagnosis of high serum creatine kinase levels in systemic lupus erythematosus.
12739036|a|We report the clinical and bioptic findings for a 57-year-old woman with severe chloroquine-induced myopathy. Since 1989, she had been suffering from systemic lupus erythematosus (SLE) with renal involvement and undergone periods of treatment with azathioprine and cyclophosphamide. Additional therapy with chloroquine (CQ) was started because of arthralgia. At the same time, slightly increased creatine kinase (CK) levels were noted. Myositis was suspected, and the patient was treated with steroids. The CK increase persisted, however, and she developed progressive muscular weakness and muscular atrophy. Routine controls revealed markedly elevated CK levels of 1,700 U/l. The neurological and electrophysiological findings were not typical of myositis. Thus, muscle biopsy of the deltoid muscle was performed in order to exclude polymyositis or toxic myopathy. As it revealed chloroquine-induced myopathy, medication was stopped. Discriminating between primary SLE-induced affection of the musculoskeletal system and drug-induced side effects is important for appropriate treatment of SLE patients.
12739036	37	45	creatine	Chemical	D003401
12739036	63	91	systemic lupus erythematosus	Disease	D008180
12739036	173	184	chloroquine	Chemical	D002738
12739036	193	201	myopathy	Disease	D009135
12739036	243	271	systemic lupus erythematosus	Disease	D008180
12739036	273	276	SLE	Disease	D008180
12739036	283	300	renal involvement	Disease	D007674
12739036	341	353	azathioprine	Chemical	D001379
12739036	358	374	cyclophosphamide	Chemical	D003520
12739036	400	411	chloroquine	Chemical	D002738
12739036	413	415	CQ	Chemical	D002738
12739036	440	450	arthralgia	Disease	D018771
12739036	489	497	creatine	Chemical	D003401
12739036	529	537	Myositis	Disease	D009220
12739036	586	594	steroids	Chemical	D013256
12739036	662	679	muscular weakness	Disease	D018908
12739036	684	700	muscular atrophy	Disease	D009133
12739036	841	849	myositis	Disease	D009220
12739036	927	939	polymyositis	Disease	D017285
12739036	949	957	myopathy	Disease	D009135
12739036	974	985	chloroquine	Chemical	D002738
12739036	994	1002	myopathy	Disease	D009135
12739036	1059	1062	SLE	Disease	D008180
12739036	1071	1110	affection of the musculoskeletal system	Disease	D009140
12739036	1183	1186	SLE	Disease	D008180
12739036	CID	D002738	D018908
12739036	CID	D002738	D009133

12093990|t|Intravenous ribavirin treatment for severe adenovirus disease in immunocompromised children.
12093990|a|BACKGROUND: Adenovirus is an important cause of morbidity and mortality in the immunocompromised host. The incidence of severe adenovirus disease in pediatrics is increasing in association with growing numbers of immunocompromised children, where case fatality rates as high as 50% to 80% have been reported. There are no approved antiviral agents with proven efficacy for the treatment of severe adenovirus disease, nor are there any prospective randomized, controlled trials of potentially useful anti-adenovirus therapies. Apparent clinical success in the treatment of severe adenovirus disease is limited to a few case reports and small series. Experience is greatest with intravenous ribavirin and cidofovir. Ribavirin, a guanosine analogue, has broad antiviral activity against both RNA and DNA viruses, including documented activity against adenovirus in vitro. Ribavirin is licensed in aerosol form for the treatment of respiratory syncytial virus infection, and orally in combination with interferon to treat hepatitis C. Intravenous ribavirin is the treatment of choice for infection with hemorrhagic fever viruses. The most common adverse effect of intravenous ribavirin is reversible mild anemia. The use of cidofovir in severe adenovirus infection has been limited by adverse effects, the most significant of which is nephrotoxicity. OBJECTIVE: We report our experience with intravenous ribavirin therapy for severe adenovirus disease in a series of immunocompromised children and review the literature. DESIGN/METHODS: We retrospectively reviewed the medical records of 5 children treated with intravenous ribavirin for documented severe adenovirus disease. Two patients developed adenovirus hemorrhagic cystitis after cardiac and bone marrow transplants, respectively. The bone marrow transplant patient also received intravenous cidofovir for progressive disseminated disease. An additional 3 children developed adenovirus pneumonia; 2 were neonates, 1 of whom had partial DiGeorge syndrome. The remaining infant had recently undergone a cardiac transplant. Intravenous ribavirin was administered on a compassionate-use protocol. RESULTS: Complete clinical recovery followed later by viral clearance was observed in 2 children: the cardiac transplant recipient with adenovirus hemorrhagic cystitis and the immunocompetent neonate with adenovirus pneumonia. The remaining 3 children died of adenovirus disease. Intravenous ribavirin therapy was well tolerated. Use of cidofovir in 1 child was associated with progressive renal failure and neutropenia. DISCUSSION: Our series of patients is representative of the spectrum of immunocompromised children at greatest risk for severe adenovirus disease, namely solid-organ and bone marrow transplant recipients, neonates, and children with immunodeficiency. Although intravenous ribavirin was not effective for all children with severe adenovirus disease in this series or in the literature, therapy is unlikely to be of benefit if begun late in the course of the infection. Early identification, eg by polymerase chain reaction of those patients at risk of disseminated adenovirus disease may permit earlier antiviral treatment and better evaluation of therapeutic response. CONCLUSIONS: Two of 5 children with severe adenovirus disease treated with intravenous ribavirin recovered. The availability of newer rapid diagnostic techniques, such as polymerase chain reaction, may make earlier, more effective treatment of adenovirus infection possible. Given the seriousness and increasing prevalence of adenovirus disease in certain hosts, especially children, a large, multicenter clinical trial of potentially useful anti-adenoviral therapies, such as intravenous ribavirin, is clearly required to demonstrate the most effective and least toxic therapy.
12093990	12	21	ribavirin	Chemical	D012254
12093990	43	61	adenovirus disease	Disease	D000257
12093990	220	238	adenovirus disease	Disease	D000257
12093990	490	508	adenovirus disease	Disease	D000257
12093990	672	690	adenovirus disease	Disease	D000257
12093990	782	791	ribavirin	Chemical	D012254
12093990	796	805	cidofovir	Chemical	C059262
12093990	807	816	Ribavirin	Chemical	D012254
12093990	820	829	guanosine	Chemical	D006151
12093990	962	971	Ribavirin	Chemical	D012254
12093990	1021	1058	respiratory syncytial virus infection	Disease	D018357
12093990	1111	1122	hepatitis C	Disease	D006526
12093990	1136	1145	ribavirin	Chemical	D012254
12093990	1177	1217	infection with hemorrhagic fever viruses	Disease	D006482
12093990	1265	1274	ribavirin	Chemical	D012254
12093990	1294	1300	anemia	Disease	D000740
12093990	1313	1322	cidofovir	Chemical	C059262
12093990	1333	1353	adenovirus infection	Disease	D000257
12093990	1424	1438	nephrotoxicity	Disease	D007674
12093990	1493	1502	ribavirin	Chemical	D012254
12093990	1522	1540	adenovirus disease	Disease	D000257
12093990	1713	1722	ribavirin	Chemical	D012254
12093990	1745	1763	adenovirus disease	Disease	D000257
12093990	1799	1819	hemorrhagic cystitis	Disease	D006470|D003556	hemorrhagic|cystitis
12093990	1938	1947	cidofovir	Chemical	C059262
12093990	2021	2041	adenovirus pneumonia	Disease	D000257|D011024	adenovirus|pneumonia
12093990	2082	2099	DiGeorge syndrome	Disease	D004062
12093990	2179	2188	ribavirin	Chemical	D012254
12093990	2386	2406	hemorrhagic cystitis	Disease	D006470|D003556	hemorrhagic|cystitis
12093990	2444	2464	adenovirus pneumonia	Disease	D000257|D011024	adenovirus|pneumonia
12093990	2499	2517	adenovirus disease	Disease	D000257
12093990	2531	2540	ribavirin	Chemical	D012254
12093990	2576	2585	cidofovir	Chemical	C059262
12093990	2617	2642	progressive renal failure	Disease	D058186
12093990	2647	2658	neutropenia	Disease	D009503
12093990	2787	2805	adenovirus disease	Disease	D000257
12093990	2893	2909	immunodeficiency	Disease	D007153
12093990	2932	2941	ribavirin	Chemical	D012254
12093990	2989	3007	adenovirus disease	Disease	D000257
12093990	3117	3126	infection	Disease	D007239
12093990	3224	3242	adenovirus disease	Disease	D000257
12093990	3372	3390	adenovirus disease	Disease	D000257
12093990	3416	3425	ribavirin	Chemical	D012254
12093990	3573	3593	adenovirus infection	Disease	D000257
12093990	3655	3673	adenovirus disease	Disease	D000257
12093990	3818	3827	ribavirin	Chemical	D012254
12093990	CID	C059262	D058186
12093990	CID	C059262	D009503

3962737|t|Hepatotoxicity of amiodarone.
3962737|a|Amiodarone has proved very effective in the treatment of otherwise resistant cardiac tachyarrhythmias. The use of amiodarone has, however, been limited due to its serious side-effects. A patient with cholestatic hepatitis due to amiodarone treatment is presented below and a review of the hepatotoxicity of amiodarone is given. It is concluded that solid evidence exists of hepatic injury due to amiodarone treatment, including steatosis, alterations resembling alcoholic hepatitis, cholestatic hepatitis and micronodular cirrhosis of the liver. Patients receiving amiodarone should be regularly screened with respect to hepatic enzyme levels. Therapy should be discontinued on the suspicion of cholestatic injury or hepatomegaly.
3962737	0	14	Hepatotoxicity	Disease	D056486
3962737	18	28	amiodarone	Chemical	D000638
3962737	30	40	Amiodarone	Chemical	D000638
3962737	115	131	tachyarrhythmias	Disease	D013610
3962737	144	154	amiodarone	Chemical	D000638
3962737	230	251	cholestatic hepatitis	Disease	D002779|D056486	cholestatic|hepatitis
3962737	259	269	amiodarone	Chemical	D000638
3962737	319	333	hepatotoxicity	Disease	D056486
3962737	337	347	amiodarone	Chemical	D000638
3962737	404	418	hepatic injury	Disease	D056486
3962737	426	436	amiodarone	Chemical	D000638
3962737	458	467	steatosis	Disease	D005234
3962737	492	511	alcoholic hepatitis	Disease	D006519
3962737	513	534	cholestatic hepatitis	Disease	D002779|D056486	cholestatic|hepatitis
3962737	552	574	cirrhosis of the liver	Disease	D008103
3962737	595	605	amiodarone	Chemical	D000638
3962737	725	743	cholestatic injury	Disease	D002779
3962737	747	759	hepatomegaly	Disease	D006529
3962737	CID	D000638	D002779
3962737	CID	D000638	D056486
3962737	CID	D000638	D008103
3962737	CID	D000638	D005234

2716967|t|Catalepsy induced by combinations of ketamine and morphine: potentiation, antagonism, tolerance and cross-tolerance in the rat.
2716967|a|Previous studies demonstrated that both ketamine and morphine induced analgesia and catalepsy in the rat. Pre-treatment with ketamine produced cross-tolerance to morphine, whereas pretreatment with morphine did not induce cross-tolerance to ketamine but rather augmented the cataleptic response; this augmentation was attributed to residual morphine in the brain. The present studies explored the duration of the loss of righting reflex induced by sub-effective doses of ketamine and morphine, administered simultaneously. There was mutual potentiation between sub-effective doses of ketamine and morphine, but sub-effective doses of ketamine partly antagonized fully-effective doses of morphine. Latency to the loss of righting reflex, rigidity and behavior on recovery, reflected the relative predominance of ketamine or morphine in each combination. Naloxone inhibited the induced cataleptic effects. The degree and time course of development of tolerance to daily administration of sub-effective dose combinations of ketamine and morphine were similar. Rats, tolerant to ketamine-dominant combinations, were cross-tolerant to both drugs, while those tolerant to morphine-dominant combinations were cross-tolerant to morphine but showed either no cross-tolerance or an augmented response to ketamine. While the mutual potentiation, antagonism and tolerance suggest common mechanisms for the induced catalepsy, differences in latency, rigidity and behavior, asymmetry of cross-tolerance and a widely-different ID50 for naloxone would argue against an action at a single opioid site.
2716967	0	9	Catalepsy	Disease	D002375
2716967	37	45	ketamine	Chemical	D007649
2716967	50	58	morphine	Chemical	D009020
2716967	168	176	ketamine	Chemical	D007649
2716967	181	189	morphine	Chemical	D009020
2716967	198	207	analgesia	Disease	D000699
2716967	212	221	catalepsy	Disease	D002375
2716967	253	261	ketamine	Chemical	D007649
2716967	290	298	morphine	Chemical	D009020
2716967	326	334	morphine	Chemical	D009020
2716967	369	377	ketamine	Chemical	D007649
2716967	403	413	cataleptic	Disease	D002375
2716967	469	477	morphine	Chemical	D009020
2716967	599	607	ketamine	Chemical	D007649
2716967	612	620	morphine	Chemical	D009020
2716967	712	720	ketamine	Chemical	D007649
2716967	725	733	morphine	Chemical	D009020
2716967	762	770	ketamine	Chemical	D007649
2716967	815	823	morphine	Chemical	D009020
2716967	865	873	rigidity	Disease	D009127
2716967	939	947	ketamine	Chemical	D007649
2716967	951	959	morphine	Chemical	D009020
2716967	981	989	Naloxone	Chemical	D009270
2716967	1012	1022	cataleptic	Disease	D002375
2716967	1149	1157	ketamine	Chemical	D007649
2716967	1162	1170	morphine	Chemical	D009020
2716967	1203	1211	ketamine	Chemical	D007649
2716967	1294	1302	morphine	Chemical	D009020
2716967	1348	1356	morphine	Chemical	D009020
2716967	1422	1430	ketamine	Chemical	D007649
2716967	1530	1539	catalepsy	Disease	D002375
2716967	1565	1573	rigidity	Disease	D009127
2716967	1649	1657	naloxone	Chemical	D009270
2716967	CID	D009020	D002375
2716967	CID	D007649	D002375

19642243|t|Acute renal failure in patients with AIDS on tenofovir while receiving prolonged vancomycin course for osteomyelitis.
19642243|a|Renal failure developed after a prolonged course of vancomycin therapy in 2 patients who were receiving tenofovir disoproxil fumarate as part of an antiretroviral regimen. Tenofovir has been implicated in the development of Fanconi syndrome and renal insufficiency because of its effects on the proximal renal tubule. Vancomycin nephrotoxicity is infrequent but may result from coadministration with a nephrotoxic agent. Clinicians should be aware that tenofovir may raise the risk of renal failure during prolonged administration of vancomycin.
19642243	0	19	Acute renal failure	Disease	D058186
19642243	37	41	AIDS	Disease	D000163
19642243	45	54	tenofovir	Chemical	C096918
19642243	81	91	vancomycin	Chemical	D014640
19642243	103	116	osteomyelitis	Disease	D010019
19642243	118	131	Renal failure	Disease	D051437
19642243	170	180	vancomycin	Chemical	D014640
19642243	222	251	tenofovir disoproxil fumarate	Chemical	C418563
19642243	290	299	Tenofovir	Chemical	C096918
19642243	342	358	Fanconi syndrome	Disease	D005198
19642243	363	382	renal insufficiency	Disease	D051437
19642243	436	446	Vancomycin	Chemical	D014640
19642243	447	461	nephrotoxicity	Disease	D007674
19642243	520	531	nephrotoxic	Disease	D007674
19642243	571	580	tenofovir	Chemical	C096918
19642243	603	616	renal failure	Disease	D051437
19642243	652	662	vancomycin	Chemical	D014640
19642243	CID	D014640	D058186
19642243	CID	C418563	D058186

17682013|t|Delayed leukoencephalopathy with stroke-like presentation in chemotherapy recipients.
17682013|a|BACKGROUND: A transient leukoencephalopathy mimicking cerebrovascular accident has been described as a complication of chemotherapy, most commonly in recipients of intrathecal methotrexate for childhood leukaemia. Recently published neuroimaging data suggest a common pathophysiology associated with a variety of chemotherapy agents and modes of administration. METHODS: We reviewed the medical literature for single reports and case series of patients presenting with stroke-like episodes while receiving systemic or intrathecal chemotherapy. We only included studies providing detailed neuroimaging data. Patients with cerebrovascular accidents were excluded. RESULTS: We identified 27 reports of toxic leukoencephalopathy in patients treated with methotrexate (intrathecal, systemic), 5-fluorouracil and its derivative carmofur, and capecitabine. Diffusion weighted imaging (DWI) of all patients revealed well demarcated hyperintense lesions within the subcortical white matter of the cerebral hemispheres and the corpus callosum, corresponding to areas of decreased proton diffusion on apparent diffusion coefficient (ADC) maps (available in 21/27 patients). Lesions exceeded the confines of adjacent vascular territories. Complete resolution of symptoms within 1-4 days was accompanied by normalisation of ADC abnormalities. However, fluid attenuated inversion recovery (FLAIR) sequences frequently revealed persistent white matter abnormalities. CONCLUSIONS: Several pathophysiological models of delayed leukoencephalopathy after exposure to intrathecal or systemic chemotherapy have been proposed. DWI findings in this cohort are indicative of cytotoxic oedema within cerebral white matter and lend support to an at least partially reversible metabolic derangement as the basis for this syndrome.
17682013	8	27	leukoencephalopathy	Disease	D056784
17682013	33	39	stroke	Disease	D020521
17682013	110	129	leukoencephalopathy	Disease	D056784
17682013	140	164	cerebrovascular accident	Disease	D002544
17682013	262	274	methotrexate	Chemical	D008727
17682013	289	298	leukaemia	Disease	D007938
17682013	555	561	stroke	Disease	D020521
17682013	707	732	cerebrovascular accidents	Disease	D002544
17682013	791	810	leukoencephalopathy	Disease	D056784
17682013	836	848	methotrexate	Chemical	D008727
17682013	874	888	5-fluorouracil	Chemical	D005472
17682013	908	916	carmofur	Chemical	C017367
17682013	922	934	capecitabine	Chemical	C110904
17682013	1023	1066	lesions within the subcortical white matter	Disease	D056784
17682013	1510	1536	white matter abnormalities	Disease	D056784
17682013	1596	1615	leukoencephalopathy	Disease	D056784
17682013	1737	1782	cytotoxic oedema within cerebral white matter	Disease	D001929
17682013	CID	D008727	D056784
17682013	CID	C017367	D056784
17682013	CID	D005472	D056784
17682013	CID	C110904	D056784

16725121|t|Down-regulation of norepinephrine transporter function induced by chronic administration of desipramine linking to the alteration of sensitivity of local-anesthetics-induced convulsions and the counteraction by co-administration with local anesthetics.
16725121|a|Alterations of norepinephrine transporter (NET) function by chronic inhibition of NET in relation to sensitization to seizures induce by cocaine and local anesthetics were studied in mice. Daily administration of desipramine, an inhibitor of the NET, for 5 days decreased [(3)H]norepinephrine uptake in the P2 fractions of hippocampus but not cortex, striatum or amygdalae. Co-administration of lidocaine, bupivacaine or tricaine with desipramine reversed this effect. Daily treatment of cocaine increased [(3)H]norepinephrine uptake into the hippocampus. Daily administration of desipramine increased the incidence of appearance of lidocaine-induced convulsions and decreased that of cocaine-induced convulsions. Co-administration of lidocaine with desipramine reversed the changes of convulsive activity of lidocaine and cocaine induced by repeated administration of desipramine. These results suggest that down-regulation of hippocampal NET induced by chronic administration of desipramine may be relevant to desipramine-induced sensitization of lidocaine convulsions. Inhibition of Na(+) channels by local anesthetics may regulate desipramine-induced down-regulation of NET function. Repeated administration of cocaine induces up-regulation of hippocampal NET function. Desipramine-induced sensitization of lidocaine seizures may have a mechanism distinct from kindling resulting from repeated administration of cocaine.
16725121	19	33	norepinephrine	Chemical	D009638
16725121	92	103	desipramine	Chemical	D003891
16725121	174	185	convulsions	Disease	D012640
16725121	268	282	norepinephrine	Chemical	D009638
16725121	371	379	seizures	Disease	D012640
16725121	390	397	cocaine	Chemical	D003042
16725121	466	477	desipramine	Chemical	D003891
16725121	531	545	norepinephrine	Chemical	D009638
16725121	648	657	lidocaine	Chemical	D008012
16725121	659	670	bupivacaine	Chemical	D002045
16725121	674	682	tricaine	Chemical	C003636
16725121	688	699	desipramine	Chemical	D003891
16725121	741	748	cocaine	Chemical	D003042
16725121	765	779	norepinephrine	Chemical	D009638
16725121	833	844	desipramine	Chemical	D003891
16725121	886	895	lidocaine	Chemical	D008012
16725121	904	915	convulsions	Disease	D012640
16725121	938	945	cocaine	Chemical	D003042
16725121	954	965	convulsions	Disease	D012640
16725121	988	997	lidocaine	Chemical	D008012
16725121	1003	1014	desipramine	Chemical	D003891
16725121	1039	1049	convulsive	Disease	D012640
16725121	1062	1071	lidocaine	Chemical	D008012
16725121	1076	1083	cocaine	Chemical	D003042
16725121	1122	1133	desipramine	Chemical	D003891
16725121	1234	1245	desipramine	Chemical	D003891
16725121	1265	1276	desipramine	Chemical	D003891
16725121	1302	1311	lidocaine	Chemical	D008012
16725121	1312	1323	convulsions	Disease	D012640
16725121	1339	1341	Na	Chemical	D012964
16725121	1388	1399	desipramine	Chemical	D003891
16725121	1468	1475	cocaine	Chemical	D003042
16725121	1527	1538	Desipramine	Chemical	D003891
16725121	1564	1573	lidocaine	Chemical	D008012
16725121	1574	1582	seizures	Disease	D012640
16725121	1669	1676	cocaine	Chemical	D003042
16725121	CID	D003042	D012640
16725121	CID	D008012	D012640

16629641|t|Definition and management of anemia in patients infected with hepatitis C virus.
16629641|a|Chronic infection with hepatitis C virus (HCV) can progress to cirrhosis, hepatocellular carcinoma, and end-stage liver disease. The current best treatment for HCV infection is combination therapy with pegylated interferon and ribavirin. Although this regimen produces sustained virologic responses (SVRs) in approximately 50% of patients, it can be associated with a potentially dose-limiting hemolytic anemia. Hemoglobin concentrations decrease mainly as a result of ribavirin-induced hemolysis, and this anemia can be problematic in patients with HCV infection, especially those who have comorbid renal or cardiovascular disorders. In general, anemia can increase the risk of morbidity and mortality, and may have negative effects on cerebral function and quality of life. Although ribavirin-associated anemia can be reversed by dose reduction or discontinuation, this approach compromises outcomes by significantly decreasing SVR rates. Recombinant human erythropoietin has been used to manage ribavirin-associated anemia but has other potential disadvantages. Viramidine, a liver-targeting prodrug of ribavirin, has the potential to maintain the virologic efficacy of ribavirin while decreasing the risk of hemolytic anemia in patients with chronic hepatitis C.
16629641	29	35	anemia	Disease	D000740
16629641	48	79	infected with hepatitis C virus	Disease	D006526
16629641	81	121	Chronic infection with hepatitis C virus	Disease	D019698
16629641	144	153	cirrhosis	Disease	D005355
16629641	155	179	hepatocellular carcinoma	Disease	D006528
16629641	185	208	end-stage liver disease	Disease	D058625
16629641	241	254	HCV infection	Disease	D006526
16629641	293	303	interferon	Chemical	D007372
16629641	308	317	ribavirin	Chemical	D012254
16629641	475	491	hemolytic anemia	Disease	D000743
16629641	550	559	ribavirin	Chemical	D012254
16629641	568	577	hemolysis	Disease	D006461
16629641	588	594	anemia	Disease	D000740
16629641	631	644	HCV infection	Disease	D006526
16629641	681	714	renal or cardiovascular disorders	Disease	D007674|D002318	renal disorders|cardiovascular disorders
16629641	728	734	anemia	Disease	D000740
16629641	866	875	ribavirin	Chemical	D012254
16629641	887	893	anemia	Disease	D000740
16629641	1079	1088	ribavirin	Chemical	D012254
16629641	1100	1106	anemia	Disease	D000740
16629641	1146	1156	Viramidine	Chemical	C026956
16629641	1187	1196	ribavirin	Chemical	D012254
16629641	1254	1263	ribavirin	Chemical	D012254
16629641	1293	1309	hemolytic anemia	Disease	D000743
16629641	1327	1346	chronic hepatitis C	Disease	D019698
16629641	CID	D012254	D000743
16629641	CID	D007372	D000743

16006300|t|Calcium carbonate toxicity: the updated milk-alkali syndrome; report of 3 cases and review of the literature.
16006300|a|OBJECTIVE: To describe 3 patients with calcium carbonate-induced hypercalcemia and gain insights into the cause and management of the milk-alkali syndrome. METHODS: We report the clinical and laboratory data in 3 patients who presented with severe hypercalcemia (corrected serum calcium > or = 14 mg/dL) and review the pertinent literature on milk-alkali syndrome. RESULTS: The 3 patients had acute renal insufficiency, relative metabolic alkalosis, and low parathyroid hormone (PTH), PTH-related peptide, and 1,25-dihydroxyvitamin D concentrations. No malignant lesion was found. Treatment included aggressive hydration and varied amounts of furosemide. The 2 patients with the higher serum calcium concentrations received pamidronate intravenously (60 and 30 mg, respectively), which caused severe hypocalcemia. Of the 3 patients, 2 were ingesting acceptable doses of elemental calcium (1 g and 2 g daily, respectively) in the form of calcium carbonate. In addition to our highlighted cases, we review the history, classification, pathophysiologic features, and treatment of milk-alkali syndrome and summarize the cases reported from early 1995 to November 2003. CONCLUSION: Milk-alkali syndrome may be a common cause of unexplained hypercalcemia and can be precipitated by small amounts of orally ingested calcium carbonate in susceptible persons. Treatment with hydration, furosemide, and discontinuation of the calcium and vitamin D source is adequate. Pamidronate treatment is associated with considerable risk for hypocalcemia, even in cases of initially severe hypercalcemia.
16006300	0	17	Calcium carbonate	Chemical	D002119
16006300	18	26	toxicity	Disease	D064420
16006300	40	60	milk-alkali syndrome	Disease	D006934
16006300	149	166	calcium carbonate	Chemical	D002119
16006300	175	188	hypercalcemia	Disease	D006934
16006300	244	264	milk-alkali syndrome	Disease	D006934
16006300	358	371	hypercalcemia	Disease	D006934
16006300	389	396	calcium	Chemical	D002118
16006300	453	473	milk-alkali syndrome	Disease	D006934
16006300	503	528	acute renal insufficiency	Disease	D058186
16006300	539	558	metabolic alkalosis	Disease	D000471
16006300	620	643	1,25-dihydroxyvitamin D	Chemical	C097949
16006300	753	763	furosemide	Chemical	D005665
16006300	802	809	calcium	Chemical	D002118
16006300	834	845	pamidronate	Chemical	C019248
16006300	910	922	hypocalcemia	Disease	D006996
16006300	990	997	calcium	Chemical	D002118
16006300	1047	1064	calcium carbonate	Chemical	D002119
16006300	1187	1207	milk-alkali syndrome	Disease	D006934
16006300	1287	1307	Milk-alkali syndrome	Disease	D006934
16006300	1345	1358	hypercalcemia	Disease	D006934
16006300	1419	1436	calcium carbonate	Chemical	D002119
16006300	1487	1497	furosemide	Chemical	D005665
16006300	1526	1533	calcium	Chemical	D002118
16006300	1538	1547	vitamin D	Chemical	D014807
16006300	1568	1579	Pamidronate	Chemical	C019248
16006300	1631	1643	hypocalcemia	Disease	D006996
16006300	1679	1692	hypercalcemia	Disease	D006934
16006300	CID	C019248	D006996
16006300	CID	D002119	D006934

11705128|t|Management strategies for ribavirin-induced hemolytic anemia in the treatment of hepatitis C: clinical and economic implications.
11705128|a|OBJECTIVES: Recently published studies have demonstrated increased efficacy and cost-effectiveness of combination therapy with interferon and alpha-2b/ribavirin compared with interferon-alpha monotherapy in the treatment of chronic hepatitis C (CHC). Combination therapy is associated with a clinically important adverse effect: ribavirin-induced hemolytic anemia (RIHA). The objective of this study was to evaluate the direct health-care costs and management of RIHA during treatment of CHC in a clinical trial setting. METHODS: A systematic literature review was conducted to synthesize information on the incidence and management of RIHA. Decision-analytic techniques were used to estimate the cost of treating RIHA. Uncertainty was evaluated using sensitivity analyses. RESULTS: RIHA, defined as a reduction in hemoglobin to less than 100 g/L, occurs in approximately 7% to 9% of patients treated with combination therapy. The standard of care for management of RIHA is reduction or discontinuation of the ribavirin dosage. We estimated the direct cost of treating clinically significant RIHA to be  170 per patient receiving combination therapy per 48-week treatment course (range  68- 692). The results of the one-way sensitivity analyses ranged from  57 to  317. In comparison, the cost of 48 weeks of combination therapy is  16,459. CONCLUSIONS: The direct cost of treating clinically significant RIHA is 1% ( 170/ 16,459) of drug treatment costs. Questions remain about the optimal dose of ribavirin and the incidence of RIHA in a real-world population. Despite these uncertainties, this initial evaluation of the direct cost of treating RIHA provides an estimate of the cost and management implications of this clinically important adverse effect.
11705128	26	35	ribavirin	Chemical	D012254
11705128	44	60	hemolytic anemia	Disease	D000743
11705128	81	92	hepatitis C	Disease	D006526
11705128	281	290	ribavirin	Chemical	D012254
11705128	305	321	interferon-alpha	Chemical	D016898
11705128	354	373	chronic hepatitis C	Disease	D019698
11705128	375	378	CHC	Disease	D019698
11705128	459	468	ribavirin	Chemical	D012254
11705128	477	493	hemolytic anemia	Disease	D000743
11705128	495	499	RIHA	Disease	D000743
11705128	593	597	RIHA	Disease	D000743
11705128	618	621	CHC	Disease	D019698
11705128	766	770	RIHA	Disease	D000743
11705128	844	848	RIHA	Disease	D000743
11705128	913	917	RIHA	Disease	D000743
11705128	1096	1100	RIHA	Disease	D000743
11705128	1140	1149	ribavirin	Chemical	D012254
11705128	1222	1226	RIHA	Disease	D000743
11705128	1535	1539	RIHA	Disease	D000743
11705128	1629	1638	ribavirin	Chemical	D012254
11705128	1660	1664	RIHA	Disease	D000743
11705128	1777	1781	RIHA	Disease	D000743
11705128	CID	D012254	D000743
11705128	CID	D016898	D000743

6540303|t|Effects of amine pretreatment on ketamine catatonia in pinealectomized or hypophysectomized animals.
6540303|a|The present studies were designed to clarify the role of catecholamines and pineal idolamines on ketamine-induced catatonia in the intact, pinealectomized or hypophysectomized chick and rat. In the pinealectomized chick, pretreatment with dopamine increased the duration of catatonia (DOC) after ketamine, but pretreatment with norepinephrine did not. The pineal indolamines exhibited mixed actions. Serotonin and N-acetyl serotonin which augmented ketamine DOC, did not do so in the absence of the pineal gland, whereas melatonin potentiated the ketamine DOC in both the intact and pinealectomized chick. Ketamine was more potent in the hypophysectomized chick and the circadian rhythm noted in the intact chick was absent; furthermore, melatonin did not augment the ketamine DOC whereas dopamine continued to do so. This study did not demonstrate a species difference regarding the role of the amines on the pineal in spite of the immature blood-brain barrier in the young chick and the intact barrier in the rat. In addition, these data indicate a direct role of the pituitary in the augmentation of ketamine DOC induced by melatonin. Furthermore, dopamine appeared to act on systems more closely involved with the induction of ketamine catatonia rather than directly on the pituitary.
6540303	11	16	amine	Chemical	D000588
6540303	33	41	ketamine	Chemical	D007649
6540303	42	51	catatonia	Disease	D002389
6540303	158	172	catecholamines	Chemical	D002395
6540303	198	206	ketamine	Chemical	D007649
6540303	215	224	catatonia	Disease	D002389
6540303	340	348	dopamine	Chemical	D004298
6540303	375	384	catatonia	Disease	D002389
6540303	397	405	ketamine	Chemical	D007649
6540303	429	443	norepinephrine	Chemical	D009638
6540303	501	510	Serotonin	Chemical	D012701
6540303	515	533	N-acetyl serotonin	Chemical	C006389
6540303	550	558	ketamine	Chemical	D007649
6540303	622	631	melatonin	Chemical	D008550
6540303	648	656	ketamine	Chemical	D007649
6540303	707	715	Ketamine	Chemical	D007649
6540303	839	848	melatonin	Chemical	D008550
6540303	869	877	ketamine	Chemical	D007649
6540303	890	898	dopamine	Chemical	D004298
6540303	997	1003	amines	Chemical	D000588
6540303	1204	1212	ketamine	Chemical	D007649
6540303	1228	1237	melatonin	Chemical	D008550
6540303	1252	1260	dopamine	Chemical	D004298
6540303	1332	1340	ketamine	Chemical	D007649
6540303	1341	1350	catatonia	Disease	D002389
6540303	CID	D008550	D002389
6540303	CID	D012701	D002389
6540303	CID	D004298	D002389
6540303	CID	D007649	D002389

3057041|t|Multicenter, double-blind, multiple-dose, parallel-groups efficacy and safety trial of azelastine, chlorpheniramine, and placebo in the treatment of spring allergic rhinitis.
3057041|a|Azelastine, a novel antiallergic medication, was compared with chlorpheniramine maleate and placebo for efficacy and safety in the treatment of spring allergic rhinitis in a multicenter, double-blind, multiple-dose, parallel-groups study. One hundred fifty-five subjects participated. Subjects ranged in age from 18 to 60 years of age and had at least a 2-year history of spring allergic rhinitis, confirmed by positive skin test to spring aeroallergens. Medications were given four times daily; the azelastine groups received 0.5, 1.0, or 2.0 mg in the morning and evening with placebo in the early and late afternoon; the chlorpheniramine group received 4.0 mg four times daily. Daily subject symptom cards were completed during a screening period to assess pretreatment symptoms and during a 4-week treatment period while subjects received study medications. Individual symptoms, total symptoms, and major symptoms were compared to determine efficacy of medication. Elicited, volunteered, and observed adverse experiences were recorded for each subject and compared among groups. Vital signs, body weights, serum chemistry values, complete blood cell counts, urine studies, and electrocardiograms were obtained for each subject and compared among groups. Symptoms relief in the group receiving the highest concentration of azelastine (2.0 mg twice daily) was statistically greater than in the placebo group during all weeks of the study. Lower doses of azelastine were statistically more effective than placebo only during portions of the first 3 weeks of the study. In contrast, although the chlorpheniramine group did have fewer symptoms than the placebo group during the study, the difference never reached statistical significance during any week of the study. There were no serious side effects in any of the treatment groups. Drowsiness and altered taste perception were increased significantly over placebo only in the high-dose azelastine group. Azelastine appears to be a safe, efficacious medication for seasonal allergic rhinitis.
3057041	87	97	azelastine	Chemical	C020976
3057041	99	115	chlorpheniramine	Chemical	D002744
3057041	149	173	spring allergic rhinitis	Disease	D006255
3057041	175	185	Azelastine	Chemical	C020976
3057041	238	262	chlorpheniramine maleate	Chemical	D002744
3057041	319	343	spring allergic rhinitis	Disease	D006255
3057041	547	571	spring allergic rhinitis	Disease	D006255
3057041	675	685	azelastine	Chemical	C020976
3057041	799	815	chlorpheniramine	Chemical	D002744
3057041	1501	1511	azelastine	Chemical	C020976
3057041	1631	1641	azelastine	Chemical	C020976
3057041	1771	1787	chlorpheniramine	Chemical	D002744
3057041	2010	2020	Drowsiness	Disease	D006970
3057041	2025	2049	altered taste perception	Disease	D013651
3057041	2114	2124	azelastine	Chemical	C020976
3057041	2132	2142	Azelastine	Chemical	C020976
3057041	2192	2218	seasonal allergic rhinitis	Disease	D006255
3057041	CID	C020976	D006970
3057041	CID	C020976	D013651

625456|t|Obsolete but dangerous antacid preparations.
625456|a|One case of acute hypercalcaemia and two of recurrent nephrolithiasis are reported in patients who had regularly consumed large amounts of calcium carbon-ate-sodium bicarbonate powders for more than 20 years. The powders had been obtained from pharmacists unknown to the patients' medical practitioners. It is suggested that these preparations were responsible for the patient's problems, and that such powders should no longer be freely obtainable.
625456	63	77	hypercalcaemia	Disease	D006934
625456	99	114	nephrolithiasis	Disease	D053040
625456	184	202	calcium carbon-ate	Chemical	D002119
625456	203	221	sodium bicarbonate	Chemical	D017693
625456	CID	D002119	D006934
625456	CID	D017693	D053040
625456	CID	D017693	D006934
625456	CID	D002119	D053040

7910951|t|Prolonged paralysis due to nondepolarizing neuromuscular blocking agents and corticosteroids.
7910951|a|The long-term use of nondepolarizing neuromuscular blocking agents (ND-NMBA) has recently been implicated as a cause of prolonged muscle weakness, although the site of the lesion and the predisposing factors have been unclear. We report 3 patients (age 37-52 years) with acute respiratory insufficiency who developed prolonged weakness following the discontinuation of ND-NMBAs. Two patients also received intravenous corticosteroids. Renal function was normal but hepatic function was impaired in all patients, and all had acidosis. Electrophysiologic studies revealed low amplitude compound motor action potentials, normal sensory studies, and fibrillations. Repetitive stimulation at 2 Hz showed a decremental response in 2 patients. The serum vecuronium level measured in 1 patient 14 days after the drug had been discontinued was 172 ng/mL. A muscle biopsy in this patient showed loss of thick, myosin filaments. The weakness in these patients is due to pathology at both the neuromuscular junction (most likely due to ND-NMBA) and muscle (most likely due to corticosteroids). Hepatic dysfunction and acidosis are contributing risk factors.
7910951	10	19	paralysis	Disease	D010243
7910951	27	72	nondepolarizing neuromuscular blocking agents	Chemical	D003473
7910951	77	92	corticosteroids	Chemical	D000305
7910951	115	160	nondepolarizing neuromuscular blocking agents	Chemical	D003473
7910951	162	169	ND-NMBA	Chemical	D003473
7910951	224	239	muscle weakness	Disease	D018908
7910951	371	396	respiratory insufficiency	Disease	D012131
7910951	421	429	weakness	Disease	D018908
7910951	463	471	ND-NMBAs	Chemical	D003473
7910951	512	527	corticosteroids	Chemical	D000305
7910951	618	626	acidosis	Disease	D000138
7910951	841	851	vecuronium	Chemical	D014673
7910951	979	1010	loss of thick, myosin filaments	Disease	D009135
7910951	1016	1024	weakness	Disease	D018908
7910951	1053	1097	pathology at both the neuromuscular junction	Disease	D009468
7910951	1118	1125	ND-NMBA	Chemical	D003473
7910951	1158	1173	corticosteroids	Chemical	D000305
7910951	1176	1195	Hepatic dysfunction	Disease	D008107
7910951	1200	1208	acidosis	Disease	D000138
7910951	CID	D003473	D018908
7910951	CID	D000305	D009135
7910951	CID	D003473	D009468

7752389|t|Prostaglandin E2-induced bladder hyperactivity in normal, conscious rats: involvement of tachykinins?
7752389|a|In normal conscious rats investigated by continuous cystometry, intravesically instilled prostaglandin (PG) E2 facilitated micturition and increased basal intravesical pressure. The effect was attenuated by both the NK1 receptor selective antagonist RP 67,580 and the NK2 receptor selective antagonist SR 48,968, given intra-arterially, suggesting that it was mediated by stimulation of both NK1 and NK2 receptors. Intra-arterially given PGE2 produced a distinct increase in bladder pressure before initiating a micturition reflex, indicating that the PG had a direct contractant effect on the detrusor smooth muscle. The effect of intra-arterial PGE2 could not be blocked by intra-arterial RP 67,580 or SR 48,968, which opens the possibility that the micturition reflex elicited by intra-arterial PGE2 was mediated by pathways other than the reflex initiated when the PG was given intravesically. The present results thus suggest that intra-arterial PGE2, given near the bladder, may initiate micturition in the normal rat chiefly by directly contracting the smooth muscle of the detrusor. However, when given intravesically, PGE2 may stimulate micturition by releasing tachykinins from nerves in and/or immediately below the urothelium. These tachykinins, in turn, initiate a micturition reflex by stimulating NK1 and NK2 receptors. Prostanoids may, via release of tachykinins, contribute to both urge and bladder hyperactivity seen in inflammatory conditions of the lower urinary tract.
7752389	0	16	Prostaglandin E2	Chemical	D015232
7752389	25	46	bladder hyperactivity	Disease	D053201
7752389	89	100	tachykinins	Chemical	D015320
7752389	191	212	prostaglandin (PG) E2	Chemical	D015232
7752389	352	361	RP 67,580	Chemical	C071693
7752389	404	413	SR 48,968	Chemical	C073839
7752389	540	544	PGE2	Chemical	D015232
7752389	654	656	PG	Chemical	D011453
7752389	749	753	PGE2	Chemical	D015232
7752389	793	802	RP 67,580	Chemical	C071693
7752389	806	815	SR 48,968	Chemical	C073839
7752389	900	904	PGE2	Chemical	D015232
7752389	971	973	PG	Chemical	D011453
7752389	1053	1057	PGE2	Chemical	D015232
7752389	1229	1233	PGE2	Chemical	D015232
7752389	1273	1284	tachykinins	Chemical	D015320
7752389	1347	1358	tachykinins	Chemical	D015320
7752389	1437	1448	Prostanoids	Chemical	D011453
7752389	1469	1480	tachykinins	Chemical	D015320
7752389	1510	1531	bladder hyperactivity	Disease	D053201
7752389	CID	D015232	D053201

6942642|t|Thiazide diuretics, hypokalemia and cardiac arrhythmias.
6942642|a|Thiazide diuretics are widely accepted as the cornerstone of antihypertensive treatment programs. Hypokalemia is a commonly encountered metabolic consequence of chronic thiazide therapy. We treated 38 patients (22 low renin, 16 normal renin) with moderate diastolic hypertension with hydrochlorothiazide (HCTC) administered on a twice daily schedule. Initial dose was 50 mg and the dose was increased at monthly intervals to 100 mg, 150 mg and 200 mg daily until blood pressure normalized. The serum K during the control period was 4.5 +/- 0.2 mEq/l an on 50, 100, 150 and 200 mg HCTZ daily 3.9 +/- 0.3, 3.4 +/- 0.2, 2.9 +/- 0.2, and 2.4 +/- 0.3 mEq/l, respectively. Corresponding figures for whole body K were 4107 +/- 208, 3722 +/- 319, 3628 +/- 257, 3551 +/- 336, and 3269 +/- 380 mEq, respectively. In 13 patients we observed the effects of HCTZ therapy (100 mg daily) on the occurrence of PVC's during rest as well as during static and dynamic exercise. During rest we observed 0.6 +/- 0.08 PVC beats/min +/- SEM and during static and dynamic exercise 0.6 +/- 0.06 and 0.8 +/- 0.15, respectively. Corresponding figures during HCTZ therapy 100 mg daily were 1.4 +/- 0.1, 3.6 +/- 0.7 and 5.7 4/- 0.8, respectively. The occurrence of PVC's correlated significantly with the fall in serum K+ observed r = 0.72, p less than 0.001. In conclusion we found that thiazide diuretics cause hypokalemia and depletion of body potassium. The more profound hypokalemia, the greater the propensity for the occurrence of PVC's.
6942642	0	8	Thiazide	Chemical	D049971
6942642	20	31	hypokalemia	Disease	D007008
6942642	36	55	cardiac arrhythmias	Disease	D001145
6942642	57	65	Thiazide	Chemical	D049971
6942642	155	166	Hypokalemia	Disease	D007008
6942642	226	234	thiazide	Chemical	D049971
6942642	313	335	diastolic hypertension	Disease	C563897
6942642	341	360	hydrochlorothiazide	Chemical	D006852
6942642	362	366	HCTC	Chemical	D006852
6942642	557	558	K	Chemical	D011188
6942642	637	641	HCTZ	Chemical	D006852
6942642	761	762	K	Chemical	D011188
6942642	902	906	HCTZ	Chemical	D006852
6942642	1188	1192	HCTZ	Chemical	D006852
6942642	1347	1348	K	Chemical	D011188
6942642	1416	1424	thiazide	Chemical	D049971
6942642	1441	1452	hypokalemia	Disease	D007008
6942642	1475	1484	potassium	Chemical	D011188
6942642	1504	1515	hypokalemia	Disease	D007008
6942642	CID	D006852	D007008
6942642	CID	D006852	D001145

3732088|t|Diuretics, potassium and arrhythmias in hypertensive coronary disease.
3732088|a|It has been proposed that modest changes in plasma potassium can alter the tendency towards cardiac arrhythmias. If this were so, patients with coronary artery disease might be especially susceptible. Thus, myocardial electrical excitability was measured in patients with mild essential hypertension and known coronary artery disease after 8 weeks of treatment with a potassium-conserving diuretic (amiloride) and a similar period on a potassium-losing diuretic (chlorthalidone) in a randomised study. Plasma potassium concentrations were on average 1 mmol/L lower during the chlorthalidone phase compared to amiloride therapy. Blood pressure and volume states as assessed by bodyweight, plasma renin and noradrenaline (norepinephrine) concentrations were similar on the 2 regimens. Compared to amiloride treatment, the chlorthalidone phase was associated with an increased frequency of ventricular ectopic beats (24-hour Holter monitoring) and a higher Lown grading, increased upslope and duration of the monophasic action potential, prolonged ventricular effective refractory period, and increased electrical instability during programmed ventricular stimulation. The above results indicate that because potassium-losing diuretic therapy can increase myocardial electrical excitability in patients with ischaemic heart disease, even minor falls in plasma potassium concentrations are probably best avoided in such patients.
3732088	11	20	potassium	Chemical	D011188
3732088	25	36	arrhythmias	Disease	D001145
3732088	40	52	hypertensive	Disease	D006973
3732088	53	69	coronary disease	Disease	D003327
3732088	122	131	potassium	Chemical	D011188
3732088	163	182	cardiac arrhythmias	Disease	D001145
3732088	215	238	coronary artery disease	Disease	D003324
3732088	358	370	hypertension	Disease	D006973
3732088	381	404	coronary artery disease	Disease	D003324
3732088	439	448	potassium	Chemical	D011188
3732088	470	479	amiloride	Chemical	D000584
3732088	507	516	potassium	Chemical	D011188
3732088	534	548	chlorthalidone	Chemical	D002752
3732088	580	589	potassium	Chemical	D011188
3732088	647	661	chlorthalidone	Chemical	D002752
3732088	680	689	amiloride	Chemical	D000584
3732088	776	789	noradrenaline	Chemical	D009638
3732088	791	805	norepinephrine	Chemical	D009638
3732088	866	875	amiloride	Chemical	D000584
3732088	891	905	chlorthalidone	Chemical	D002752
3732088	958	983	ventricular ectopic beats	Disease	D018879
3732088	1277	1286	potassium	Chemical	D011188
3732088	1376	1399	ischaemic heart disease	Disease	D017202
3732088	1428	1437	potassium	Chemical	D011188
3732088	CID	D002752	D018879

2893236|t|GABA involvement in naloxone induced reversal of respiratory paralysis produced by thiopental.
2893236|a|No agent is yet available to reverse respiratory paralysis produced by CNS depressants, such as general anesthetics. In this study naloxone reversed respiratory paralysis induced by thiopental in rats. 25 mg/kg, i.v. thiopental produced anesthesia without altering respiratory rate, increased GABA, decreased glutamate, and had no effect on aspartate or glycine levels compared to controls in rat cortex and brain stem. Pretreatment of rats with thiosemicarbazide for 30 minutes abolished the anesthetic action as well as the respiratory depressant action of thiopental. 50 mg/kg, i.v. thiopental produced respiratory arrest with further increase in GABA and decrease in glutamate again in cortex and brain stem without affecting any of the amino acids studied in four regions of rat brain. Naloxone (2.5 mg/kg, i.v.) reversed respiratory paralysis, glutamate and GABA levels to control values in brain stem and cortex with no changes in caudate or cerebellum. These data suggest naloxone reverses respiratory paralysis produced by thiopental and involves GABA in its action.
2893236	0	4	GABA	Chemical	D005680
2893236	20	28	naloxone	Chemical	D009270
2893236	49	70	respiratory paralysis	Disease	D012133
2893236	83	93	thiopental	Chemical	D013874
2893236	132	153	respiratory paralysis	Disease	D012133
2893236	226	234	naloxone	Chemical	D009270
2893236	244	265	respiratory paralysis	Disease	D012133
2893236	277	287	thiopental	Chemical	D013874
2893236	312	322	thiopental	Chemical	D013874
2893236	388	392	GABA	Chemical	D005680
2893236	404	413	glutamate	Chemical	D018698
2893236	436	445	aspartate	Chemical	D001224
2893236	449	456	glycine	Chemical	D005998
2893236	541	558	thiosemicarbazide	Chemical	C005151
2893236	654	664	thiopental	Chemical	D013874
2893236	681	691	thiopental	Chemical	D013874
2893236	701	719	respiratory arrest	Disease	D012131
2893236	745	749	GABA	Chemical	D005680
2893236	766	775	glutamate	Chemical	D018698
2893236	836	847	amino acids	Chemical	D000596
2893236	886	894	Naloxone	Chemical	D009270
2893236	922	943	respiratory paralysis	Disease	D012133
2893236	945	954	glutamate	Chemical	D018698
2893236	959	963	GABA	Chemical	D005680
2893236	1075	1083	naloxone	Chemical	D009270
2893236	1093	1114	respiratory paralysis	Disease	D012133
2893236	1127	1137	thiopental	Chemical	D013874
2893236	1151	1155	GABA	Chemical	D005680
2893236	CID	D013874	D012133

2533791|t|National project on the prevention of mother-to-infant infection by hepatitis B virus in Japan.
2533791|a|In Japan, a nationwide prevention program against mother-to-infant infection by hepatitis B virus (HBV) started in 1985. This program consists of double screenings of pregnant women and prophylactic treatment to the infants born to both hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) positive mothers. These infants are treated with two injections of hepatitis B immune globulin (HBIG) and at least three injections of plasma derived hepatitis B vaccine. We sent questionnaires about the numbers of each procedure or examination during nine months of investigation period to each local government in 1986 and 1987. 93.4% pregnant women had the chance to be examined for HBsAg, and the positive rate was 1.4 to 1.5%. The HBeAg positive rate in HBsAg positive was 23 to 26%. The HBsAg positive rate in neonates and in infants before two months were 3% and 2% respectively. Some problems may arise, because 27 to 30% of infants need the fourth vaccination in some restricted areas.
2533791	55	85	infection by hepatitis B virus	Disease	D006509
2533791	163	193	infection by hepatitis B virus	Disease	D006509
2533791	333	360	hepatitis B surface antigen	Chemical	D006514
2533791	362	367	HBsAg	Chemical	D006514
2533791	373	394	hepatitis B e antigen	Chemical	D006513
2533791	396	401	HBeAg	Chemical	D006513
2533791	470	481	hepatitis B	Disease	D006509
2533791	553	572	hepatitis B vaccine	Chemical	D017325
2533791	789	794	HBsAg	Chemical	D006514
2533791	839	844	HBeAg	Chemical	D006513
2533791	862	867	HBsAg	Chemical	D006514
2533791	896	901	HBsAg	Chemical	D006514
2533791	CID	D006513	D006509
2533791	CID	D006514	D006509

2322844|t|Nociceptive effects induced by intrathecal administration of prostaglandin D2, E2, or F2 alpha to conscious mice.
2322844|a|The effects of intrathecal administration of prostaglandins on pain responses in conscious mice were evaluated by using hot plate and acetic acid writhing tests. Prostaglandin D2 (0.5-3 ng/mouse) had a hyperalgesic action on the response to a hot plate during a 3-60 min period after injection. Prostaglandin E2 showed a hyperalgesic effect at doses of 1 pg to 10 ng/mouse, but the effect lasted shorter (3-30 min) than that of prostaglandin D2. Similar results were obtained by acetic acid writhing tests. The hyperalgesic effect of prostaglandin D2 was blocked by simultaneous injection of a substance P antagonist (greater than or equal to 100 ng) but not by AH6809, a prostanoid EP1-receptor antagonist. Conversely, prostaglandin E2-induced hyperalgesia was blocked by AH6809 (greater than or equal to 500 ng) but not by the substance P antagonist. Prostaglandin F2 alpha had little effect on pain responses. These results demonstrate that both prostaglandin D2 and prostaglandin E2 exert hyperalgesia in the spinal cord, but in different ways.
2322844	61	94	prostaglandin D2, E2, or F2 alpha	Chemical	D015230|D015232|D015237	prostaglandin D2|prostaglandin E2|prostaglandin F2 alpha
2322844	159	173	prostaglandins	Chemical	D011453
2322844	177	181	pain	Disease	D010146
2322844	248	259	acetic acid	Chemical	D019342
2322844	276	292	Prostaglandin D2	Chemical	D015230
2322844	316	328	hyperalgesic	Disease	D006930
2322844	409	425	Prostaglandin E2	Chemical	D015232
2322844	435	447	hyperalgesic	Disease	D006930
2322844	469	471	pg	Chemical	D011453
2322844	542	558	prostaglandin D2	Chemical	D015230
2322844	593	604	acetic acid	Chemical	D019342
2322844	625	637	hyperalgesic	Disease	D006930
2322844	648	664	prostaglandin D2	Chemical	D015230
2322844	776	782	AH6809	Chemical	C053876
2322844	834	850	prostaglandin E2	Chemical	D015232
2322844	859	871	hyperalgesia	Disease	D006930
2322844	887	893	AH6809	Chemical	C053876
2322844	967	989	Prostaglandin F2 alpha	Chemical	D015237
2322844	1011	1015	pain	Disease	D010146
2322844	1063	1079	prostaglandin D2	Chemical	D015230
2322844	1084	1100	prostaglandin E2	Chemical	D015232
2322844	1107	1119	hyperalgesia	Disease	D006930
2322844	CID	D015232	D006930
2322844	CID	D015230	D006930

20552622|t|Swallowing-induced atrial tachyarrhythmia triggered by salbutamol: case report and review of the literature.
20552622|a|CASE: A 49-year-old patient experienced chest discomfort while swallowing. On electrocardiogram, episodes of atrial tachyarrhythmia were recorded immediately after swallowing; 24-hour Holter monitoring recorded several events. The arrhythmia resolved after therapy with atenolol, but recurred a year later. The patient noticed that before these episodes he had been using an inhalator of salbutamol. After stopping the beta-agonist, and after a week with the atenolol, the arrhythmia disappeared. DISCUSSION: Swallowing-induced atrial tachyarrhythmia (SIAT) is a rare phenomenon. Fewer than 50 cases of SIAT have been described in the literature. This article summarizes all the cases published, creating a comprehensive review of the current knowledge and approach to SIAT. It discusses demographics, clinical characteristics and types of arrhythmia, postulated mechanisms of SIAT, and different treatment possibilities such as medications, surgery, and radiofrequency catheter ablation (RFCA). CONCLUSION: Salbutamol is presented here as a possible trigger for SIAT. Although it is difficult to define causality in a case report, it is logical to think that a beta-agonist like salbutamol (known to induce tachycardia) may be the trigger of adrenergic reflexes originating in the esophagus while swallowing and that a beta-blocker such as atenolol (that blocks the adrenergic activity) may relieve it.
20552622	19	41	atrial tachyarrhythmia	Disease	D013617
20552622	55	65	salbutamol	Chemical	D000420
20552622	218	240	atrial tachyarrhythmia	Disease	D013617
20552622	340	350	arrhythmia	Disease	D001145
20552622	379	387	atenolol	Chemical	D001262
20552622	497	507	salbutamol	Chemical	D000420
20552622	568	576	atenolol	Chemical	D001262
20552622	582	592	arrhythmia	Disease	D001145
20552622	637	659	atrial tachyarrhythmia	Disease	D013617
20552622	661	665	SIAT	Disease	D013617
20552622	712	716	SIAT	Disease	D013617
20552622	878	882	SIAT	Disease	D013617
20552622	949	959	arrhythmia	Disease	D001145
20552622	986	990	SIAT	Disease	D013617
20552622	1117	1127	Salbutamol	Chemical	D000420
20552622	1172	1176	SIAT	Disease	D013617
20552622	1289	1299	salbutamol	Chemical	D000420
20552622	1317	1328	tachycardia	Disease	D013610
20552622	1450	1458	atenolol	Chemical	D001262
20552622	CID	D000420	D013617

20510337|t|Coenzyme Q10 treatment ameliorates acute cisplatin nephrotoxicity in mice.
20510337|a|The nephroprotective effect of coenzyme Q10 was investigated in mice with acute renal injury induced by a single i.p. injection of cisplatin (5 mg/kg). Coenzyme Q10 treatment (10 mg/kg/day, i.p.) was applied for 6 consecutive days, starting 1 day before cisplatin administration. Coenzyme Q10 significantly reduced blood urea nitrogen and serum creatinine levels which were increased by cisplatin. Coenzyme Q10 significantly compensated deficits in the antioxidant defense mechanisms (reduced glutathione level and superoxide dismutase activity), suppressed lipid peroxidation, decreased the elevations of tumor necrosis factor-alpha, nitric oxide and platinum ion concentration, and attenuated the reductions of selenium and zinc ions in renal tissue resulted from cisplatin administration. Also, histopathological renal tissue damage mediated by cisplatin was ameliorated by coenzyme Q10 treatment. Immunohistochemical analysis revealed that coenzyme Q10 significantly decreased the cisplatin-induced overexpression of inducible nitric oxide synthase, nuclear factor-kappaB, caspase-3 and p53 in renal tissue. It was concluded that coenzyme Q10 represents a potential therapeutic option to protect against acute cisplatin nephrotoxicity commonly encountered in clinical practice.
20510337	0	12	Coenzyme Q10	Chemical	C024989
20510337	41	50	cisplatin	Chemical	D002945
20510337	51	65	nephrotoxicity	Disease	D007674
20510337	106	118	coenzyme Q10	Chemical	C024989
20510337	149	167	acute renal injury	Disease	D058186
20510337	206	215	cisplatin	Chemical	D002945
20510337	227	239	Coenzyme Q10	Chemical	C024989
20510337	329	338	cisplatin	Chemical	D002945
20510337	355	367	Coenzyme Q10	Chemical	C024989
20510337	390	409	blood urea nitrogen	Chemical	D001806
20510337	420	430	creatinine	Chemical	D003404
20510337	462	471	cisplatin	Chemical	D002945
20510337	473	485	Coenzyme Q10	Chemical	C024989
20510337	560	579	reduced glutathione	Chemical	D005978
20510337	590	600	superoxide	Chemical	D013481
20510337	681	686	tumor	Disease	D009369
20510337	687	695	necrosis	Disease	D009336
20510337	710	722	nitric oxide	Chemical	D009569
20510337	727	735	platinum	Chemical	D010984
20510337	788	796	selenium	Chemical	D012643
20510337	801	805	zinc	Chemical	D015032
20510337	841	850	cisplatin	Chemical	D002945
20510337	891	910	renal tissue damage	Disease	D007674
20510337	923	932	cisplatin	Chemical	D002945
20510337	952	964	coenzyme Q10	Chemical	C024989
20510337	1019	1031	coenzyme Q10	Chemical	C024989
20510337	1060	1069	cisplatin	Chemical	D002945
20510337	1106	1118	nitric oxide	Chemical	D009569
20510337	1209	1221	coenzyme Q10	Chemical	C024989
20510337	1289	1298	cisplatin	Chemical	D002945
20510337	1299	1313	nephrotoxicity	Disease	D007674
20510337	CID	D002945	D058186

20164825|t|Metformin prevents experimental gentamicin-induced nephropathy by a mitochondria-dependent pathway.
20164825|a|The antidiabetic drug metformin can diminish apoptosis induced by oxidative stress in endothelial cells and prevent vascular dysfunction even in nondiabetic patients. Here we tested whether it has a beneficial effect in a rat model of gentamicin toxicity. Mitochondrial analysis, respiration intensity, levels of reactive oxygen species, permeability transition, and cytochrome c release were assessed 3 and 6 days after gentamicin administration. Metformin treatment fully blocked gentamicin-mediated acute renal failure. This was accompanied by a lower activity of N-acetyl-beta-D-glucosaminidase, together with a decrease of lipid peroxidation and increase of antioxidant systems. Metformin also protected the kidney from histological damage 6 days after gentamicin administration. These in vivo markers of kidney dysfunction and their correction by metformin were complemented by in vitro studies of mitochondrial function. We found that gentamicin treatment depleted respiratory components (cytochrome c, NADH), probably due to the opening of mitochondrial transition pores. These injuries, partly mediated by a rise in reactive oxygen species from the electron transfer chain, were significantly decreased by metformin. Thus, our study suggests that pleiotropic effects of metformin can lessen gentamicin nephrotoxicity and improve mitochondrial homeostasis.
20164825	0	9	Metformin	Chemical	D008687
20164825	32	42	gentamicin	Chemical	D005839
20164825	51	62	nephropathy	Disease	D007674
20164825	122	131	metformin	Chemical	D008687
20164825	216	236	vascular dysfunction	Disease	D014652
20164825	335	345	gentamicin	Chemical	D005839
20164825	346	354	toxicity	Disease	D064420
20164825	422	428	oxygen	Chemical	D010100
20164825	521	531	gentamicin	Chemical	D005839
20164825	548	557	Metformin	Chemical	D008687
20164825	582	592	gentamicin	Chemical	D005839
20164825	602	621	acute renal failure	Disease	D058186
20164825	784	793	Metformin	Chemical	D008687
20164825	858	868	gentamicin	Chemical	D005839
20164825	910	928	kidney dysfunction	Disease	D007674
20164825	953	962	metformin	Chemical	D008687
20164825	1042	1052	gentamicin	Chemical	D005839
20164825	1234	1240	oxygen	Chemical	D010100
20164825	1315	1324	metformin	Chemical	D008687
20164825	1379	1388	metformin	Chemical	D008687
20164825	1400	1410	gentamicin	Chemical	D005839
20164825	1411	1425	nephrotoxicity	Disease	D007674
20164825	CID	D005839	D058186

20042557|t|Sedation depth during spinal anesthesia and the development of postoperative delirium in elderly patients undergoing hip fracture repair.
20042557|a|OBJECTIVE: To determine whether limiting intraoperative sedation depth during spinal anesthesia for hip fracture repair in elderly patients can decrease the prevalence of postoperative delirium. PATIENTS AND METHODS: We performed a double-blind, randomized controlled trial at an academic medical center of elderly patients (>or=65 years) without preoperative delirium or severe dementia who underwent hip fracture repair under spinal anesthesia with propofol sedation. Sedation depth was titrated using processed electroencephalography with the bispectral index (BIS), and patients were randomized to receive either deep (BIS, approximately 50) or light (BIS, >or=80) sedation. Postoperative delirium was assessed as defined by Diagnostic and Statistical Manual of Mental Disorders (Third Edition Revised) criteria using the Confusion Assessment Method beginning at any time from the second day after surgery. RESULTS: From April 2, 2005, through October 30, 2008, a total of 114 patients were randomized. The prevalence of postoperative delirium was significantly lower in the light sedation group (11/57 [19%] vs 23/57 [40%] in the deep sedation group; P=.02), indicating that 1 incident of delirium will be prevented for every 4.7 patients treated with light sedation. The mean +/- SD number of days of delirium during hospitalization was lower in the light sedation group than in the deep sedation group (0.5+/-1.5 days vs 1.4+/-4.0 days; P=.01). CONCLUSION: The use of light propofol sedation decreased the prevalence of postoperative delirium by 50% compared with deep sedation. Limiting depth of sedation during spinal anesthesia is a simple, safe, and cost-effective intervention for preventing postoperative delirium in elderly patients that could be widely and readily adopted.
20042557	63	85	postoperative delirium	Disease	D011183|D003693	postoperative delirium|delirium
20042557	117	129	hip fracture	Disease	D006620
20042557	238	250	hip fracture	Disease	D006620
20042557	309	331	postoperative delirium	Disease	D011183|D003693	postoperative delirium|delirium
20042557	498	506	delirium	Disease	D003693
20042557	517	525	dementia	Disease	D003704
20042557	540	552	hip fracture	Disease	D006620
20042557	589	597	propofol	Chemical	D015742
20042557	817	839	Postoperative delirium	Disease	D011183|D003693	Postoperative delirium|delirium
20042557	904	920	Mental Disorders	Disease	D001523
20042557	1163	1185	postoperative delirium	Disease	D011183|D003693	postoperative delirium|delirium
20042557	1332	1340	delirium	Disease	D003693
20042557	1445	1453	delirium	Disease	D003693
20042557	1619	1627	propofol	Chemical	D015742
20042557	1665	1687	postoperative delirium	Disease	D011183|D003693	postoperative delirium|delirium
20042557	1842	1864	postoperative delirium	Disease	D011183|D003693	postoperative delirium|delirium
20042557	CID	D015742	D003693
20042557	CID	D015742	D011183

19944333|t|Sorafenib-induced acute myocardial infarction due to coronary artery spasm.
19944333|a|A 65-year-old man with advanced renal cell carcinoma was admitted due to continuing chest pain at rest. Two weeks before his admission, sorafenib had been started. He was diagnosed with non-ST-elevation myocardial infarction by laboratory data and electrocardiogram. Enhanced heart magnetic resonance imaging also showed subendocardial infarction. However, there was no stenosis in coronary arteries on angiography. Coronary artery spasm was induced by a provocative test. Cessation of sorafenib and administration of Ca-channel blocker and nitrates ameliorated his symptoms, but relapse occurred after resumption of sorafenib. Addition of oral nicorandil reduced his symptoms and maintained stable angina status. We report the first case of sorafenib-induced coronary artery spasm. Sorafenib is a multikinase inhibitor that targets signaling pathways necessary for cellular proliferation and survival. On the other hand, the Rho/ROCK pathway has an important role in the pathogenesis of coronary artery spasm. Our report may show an adverse effect on the Rho/ROCK pathway by sorafenib use.
19944333	0	9	Sorafenib	Chemical	C471405
19944333	24	45	myocardial infarction	Disease	D009203
19944333	53	74	coronary artery spasm	Disease	D003329
19944333	108	128	renal cell carcinoma	Disease	D002292
19944333	160	170	chest pain	Disease	D002637
19944333	212	221	sorafenib	Chemical	C471405
19944333	279	300	myocardial infarction	Disease	D009203
19944333	397	422	subendocardial infarction	Disease	D009203
19944333	492	513	Coronary artery spasm	Disease	D003329
19944333	562	571	sorafenib	Chemical	C471405
19944333	594	596	Ca	Chemical	D002118
19944333	617	625	nitrates	Chemical	D009566
19944333	693	702	sorafenib	Chemical	C471405
19944333	721	731	nicorandil	Chemical	D020108
19944333	768	781	stable angina	Disease	D060050
19944333	818	827	sorafenib	Chemical	C471405
19944333	836	857	coronary artery spasm	Disease	D003329
19944333	859	868	Sorafenib	Chemical	C471405
19944333	1064	1085	coronary artery spasm	Disease	D003329
19944333	1152	1161	sorafenib	Chemical	C471405
19944333	CID	C471405	D003329

17975693|t|Anxiogenic potential of ciprofloxacin and norfloxacin in rats.
17975693|a|INTRODUCTION: The possible anxiogenic effects of fluoroquinolones, namely ciprofloxacin and norfloxacin, were investigated in adult Charles Foster albino rats of either sex, weighing 150-200 g. METHODS: The drugs were given orally, in doses of 50 mg/kg for five consecutive days and the experiments were performed on the fifth day. The tests included open-field exploratory behaviour, elevated plus maze and elevated zero maze, social interaction and novelty-suppressed feeding latency behaviour. RESULTS: The results indicate that ciprofloxacin- and norfloxacin-treated rats showed anxious behaviour in comparison to control rats in all the parameters studied. However, ciprofloxacin- and norfloxacin-treated rats did not differ significantly from each other in various behavioural parameters. CONCLUSION: The present experimental findings substantiate the clinically observed anxiogenic potential of ciprofloxacin and norfloxacin.
17975693	24	37	ciprofloxacin	Chemical	D002939
17975693	42	53	norfloxacin	Chemical	D009643
17975693	112	128	fluoroquinolones	Chemical	D024841
17975693	137	150	ciprofloxacin	Chemical	D002939
17975693	155	166	norfloxacin	Chemical	D009643
17975693	595	608	ciprofloxacin	Chemical	D002939
17975693	614	625	norfloxacin	Chemical	D009643
17975693	646	663	anxious behaviour	Disease	D001008
17975693	734	747	ciprofloxacin	Chemical	D002939
17975693	753	764	norfloxacin	Chemical	D009643
17975693	965	978	ciprofloxacin	Chemical	D002939
17975693	983	994	norfloxacin	Chemical	D009643
17975693	CID	D009643	D001008
17975693	CID	D002939	D001008

17943461|t|Myocardial Fas ligand expression increases susceptibility to AZT-induced cardiomyopathy.
17943461|a|BACKGROUND: Dilated cardiomyopathy (DCM) and myocarditis occur in many HIV-infected individuals, resulting in symptomatic heart failure in up to 5% of patients. Highly active antiretroviral therapy (HAART) has significantly reduced morbidity and mortality of acquired immunodeficiency syndrome (AIDS), but has resulted in an increase in cardiac and skeletal myopathies. METHODS AND RESULTS: In order to investigate whether the HAART component zidovudine (3'-azido-2',3'-deoxythymidine; AZT) triggers the Fas-dependent cell-death pathway and cause cytoskeletal disruption in a murine model of DCM, 8-week-old transgenic (expressing Fas ligand in the myocardium: FasL Tg) and non-transgenic (NTg) mice received water ad libitum containing different concentrations of AZT (0, 0.07, 0.2, and 0.7 mg/ml). After 6 weeks, cardiac function was assessed by echocardiography and morphology was assessed by histopathologic and immunohistochemical methods. NTg and untreated FasL Tg mice showed little or no change in cardiac structure or function. In contrast, AZT-treated FasL Tg mice developed cardiac dilation and depressed cardiac function in a dose-dependent manner, with concomitant inflammatory infiltration of both ventricles. These changes were associated with an increased sarcolemmal expression of Fas and FasL, as well as increased activation of caspase 3, translocation of calpain 1 to the sarcolemma and sarcomere, and increased numbers of cells undergoing apoptosis. These were associated with changes in dystrophin and cardiac troponin I localization, as well as loss of sarcolemmal integrity. CONCLUSIONS: The expression of Fas ligand in the myocardium, as identified in HIV-positive patients, might increase the susceptibility to HAART-induced cardiomyopathy due to activation of apoptotic pathways, resulting in cardiac dilation and dysfunction.
17943461	61	64	AZT	Chemical	D015215
17943461	73	87	cardiomyopathy	Disease	D009202
17943461	101	123	Dilated cardiomyopathy	Disease	D002311
17943461	125	128	DCM	Disease	D002311
17943461	134	145	myocarditis	Disease	D009205
17943461	160	172	HIV-infected	Disease	D015658
17943461	211	224	heart failure	Disease	D006333
17943461	348	382	acquired immunodeficiency syndrome	Disease	D000163
17943461	384	388	AIDS	Disease	D000163
17943461	426	457	cardiac and skeletal myopathies	Disease	C538496
17943461	532	542	zidovudine	Chemical	D015215
17943461	544	573	3'-azido-2',3'-deoxythymidine	Chemical	D015215
17943461	575	578	AZT	Chemical	D015215
17943461	681	684	DCM	Disease	D002311
17943461	854	857	AZT	Chemical	D015215
17943461	1139	1142	AZT	Chemical	D015215
17943461	1174	1190	cardiac dilation	Disease	D002311
17943461	1840	1854	cardiomyopathy	Disease	D009202
17943461	1909	1941	cardiac dilation and dysfunction	Disease	D002311|D006331	cardiac dilation|cardiac dysfunction
17943461	CID	D015215	D002311
17943461	CID	D015215	D009202

17074608|t|Valproate-induced chorea and encephalopathy in atypical nonketotic hyperglycinemia.
17074608|a|Nonketotic hyperglycinemia is a disorder of amino acid metabolism in which a defect in the glycine cleavage system leads to an accumulation of glycine in the brain and other body compartments. In the classical form it presents as neonatal apnea, intractable seizures, and hypotonia, followed by significant psychomotor retardation. An important subset of children with nonketotic hyperglycinemia are atypical variants who present in a heterogeneous manner. This report describes a patient with mild language delay and mental retardation, who was found to have nonketotic hyperglycinemia following her presentation with acute encephalopathy and chorea shortly after initiation of valproate therapy.
17074608	0	9	Valproate	Chemical	D014635
17074608	18	24	chorea	Disease	D002819
17074608	29	43	encephalopathy	Disease	D001927
17074608	56	82	nonketotic hyperglycinemia	Disease	D020158
17074608	84	110	Nonketotic hyperglycinemia	Disease	D020158
17074608	116	149	disorder of amino acid metabolism	Disease	D000592
17074608	175	182	glycine	Chemical	D005998
17074608	227	234	glycine	Chemical	D005998
17074608	323	328	apnea	Disease	D001049
17074608	342	350	seizures	Disease	D012640
17074608	356	365	hypotonia	Disease	D009123
17074608	391	414	psychomotor retardation	Disease	D011596
17074608	453	479	nonketotic hyperglycinemia	Disease	D020158
17074608	583	597	language delay	Disease	D007805
17074608	602	620	mental retardation	Disease	D008607
17074608	644	670	nonketotic hyperglycinemia	Disease	D020158
17074608	709	723	encephalopathy	Disease	D001927
17074608	728	734	chorea	Disease	D002819
17074608	763	772	valproate	Chemical	D014635
17074608	CID	D014635	D002819
17074608	CID	D014635	D001927

16364460|t|Microinjection of ritanserin into the CA1 region of hippocampus improves scopolamine-induced amnesia in adult male rats.
16364460|a|The effect of ritanserin (5-HT2 antagonist) on scopolamine (muscarinic cholinergic antagonist)-induced amnesia in Morris water maze (MWM) was investigated. Rats were divided into eight groups and bilaterally cannulated into CA1 region of the hippocampus. One week later, they received repeatedly vehicles (saline, DMSO, saline+DMSO), scopolamine (2 microg/0.5 microl saline/side; 30 min before training), ritanserin (2, 4 and 8 microg/0.5 microl DMSO/side; 20 min before training) and scopolamine (2 microg/0.5 microl; 30 min before ritanserin injection)+ritanserin (4 microg/0.5 microl DMSO) through cannulae each day. Animals were tested for four consecutive days (4 trial/day) in MWM during which the position of hidden platform was unchanged. In the fifth day, the platform was elevated above the water surface in another position to evaluate the function of motor, motivational and visual systems. The results showed a significant increase in escape latencies and traveled distances to find platform in scopolamine-treated group as compared to saline group. Ritanserin-treated rats (4 microg/0.5 microl/side) showed a significant decrease in the mentioned parameters as compared to DMSO-treated group. However, scopolamine and ritanserin co-administration resulted in a significant decrease in escape latencies and traveled distances as compared to the scopolamine-treated rats. Our findings show that microinjection of ritanserin into the CA1 region of the hippocampus improves the scopolamine-induced amnesia.
16364460	18	28	ritanserin	Chemical	D016713
16364460	73	84	scopolamine	Chemical	D012601
16364460	93	100	amnesia	Disease	D000647
16364460	135	145	ritanserin	Chemical	D016713
16364460	168	179	scopolamine	Chemical	D012601
16364460	224	231	amnesia	Disease	D000647
16364460	435	439	DMSO	Chemical	D004121
16364460	448	452	DMSO	Chemical	D004121
16364460	455	466	scopolamine	Chemical	D012601
16364460	526	536	ritanserin	Chemical	D016713
16364460	567	571	DMSO	Chemical	D004121
16364460	606	617	scopolamine	Chemical	D012601
16364460	654	664	ritanserin	Chemical	D016713
16364460	676	686	ritanserin	Chemical	D016713
16364460	708	712	DMSO	Chemical	D004121
16364460	1129	1140	scopolamine	Chemical	D012601
16364460	1184	1194	Ritanserin	Chemical	D016713
16364460	1308	1312	DMSO	Chemical	D004121
16364460	1337	1348	scopolamine	Chemical	D012601
16364460	1353	1363	ritanserin	Chemical	D016713
16364460	1479	1490	scopolamine	Chemical	D012601
16364460	1546	1556	ritanserin	Chemical	D016713
16364460	1609	1620	scopolamine	Chemical	D012601
16364460	1629	1636	amnesia	Disease	D000647
16364460	CID	D012601	D000647

15579441|t|Hypoxia in renal disease with proteinuria and/or glomerular hypertension.
15579441|a|Despite the increasing need to identify and quantify tissue oxygenation at the cellular level, relatively few methods have been available. In this study, we developed a new hypoxia-responsive reporter vector using a hypoxia-responsive element of the 5' vascular endothelial growth factor untranslated region and generated a novel hypoxia-sensing transgenic rat. We then applied this animal model to the detection of tubulointerstitial hypoxia in the diseased kidney. With this model, we were able to identify diffuse cortical hypoxia in the puromycin aminonucleoside-induced nephrotic syndrome and focal and segmental hypoxia in the remnant kidney model. Expression of the hypoxia-responsive transgene increased throughout the observation period, reaching 2.2-fold at 2 weeks in the puromycin aminonucleoside model and 2.6-fold at 4 weeks in the remnant kidney model, whereas that of vascular endothelial growth factor showed a mild decrease, reflecting distinct behaviors of the two genes. The degree of hypoxia showed a positive correlation with microscopic tubulointerstitial injury in both models. Finally, we identified the localization of proliferating cell nuclear antigen-positive, ED-1-positive, and terminal dUTP nick-end labeled-positive cells in the hypoxic cortical area in the remnant kidney model. We propose here a possible pathological tie between chronic tubulointerstitial hypoxia and progressive glomerular diseases.
15579441	0	7	Hypoxia	Disease	D000860
15579441	11	24	renal disease	Disease	D007674
15579441	30	41	proteinuria	Disease	D011507
15579441	60	72	hypertension	Disease	D006973
15579441	247	254	hypoxia	Disease	D000860
15579441	290	297	hypoxia	Disease	D000860
15579441	404	411	hypoxia	Disease	D000860
15579441	509	516	hypoxia	Disease	D000860
15579441	524	539	diseased kidney	Disease	D007674
15579441	600	607	hypoxia	Disease	D000860
15579441	615	640	puromycin aminonucleoside	Chemical	D011692
15579441	649	667	nephrotic syndrome	Disease	D009404
15579441	692	699	hypoxia	Disease	D000860
15579441	747	754	hypoxia	Disease	D000860
15579441	857	882	puromycin aminonucleoside	Chemical	D011692
15579441	1079	1086	hypoxia	Disease	D000860
15579441	1134	1159	tubulointerstitial injury	Disease	-1
15579441	1336	1343	hypoxic	Disease	D000860
15579441	1466	1473	hypoxia	Disease	D000860
15579441	1490	1509	glomerular diseases	Disease	D007674
15579441	CID	D011692	D000860
15579441	CID	D011692	D009404

15517007|t|Consensus statement concerning cardiotoxicity occurring during haematopoietic stem cell transplantation in the treatment of autoimmune diseases, with special reference to systemic sclerosis and multiple sclerosis.
15517007|a|Autologous haematopoietic stem cell transplantation is now a feasible and effective treatment for selected patients with severe autoimmune diseases. Worldwide, over 650 patients have been transplanted in the context of phase I and II clinical trials. The results are encouraging enough to begin randomised phase III trials. However, as predicted, significant transplant-related morbidity and mortality have been observed. This is primarily due to complications related to either the stage of the disease at transplant or due to infections. The number of deaths related to cardiac toxicity is low. However, caution is required when cyclophosphamide or anthracyclines such as mitoxantrone are used in patients with a possible underlying heart damage, for example, systemic sclerosis patients. In November 2002, a meeting was held in Florence, bringing together a number of experts in various fields, including rheumatology, cardiology, neurology, pharmacology and transplantation medicine. The object of the meeting was to analyse existing data, both published or available, in the European Group for Blood and Marrow Transplantation autoimmune disease database, and to propose a safe approach to such patients. A full cardiological assessment before and during the transplant emerged as the major recommendation.
15517007	31	45	cardiotoxicity	Disease	D066126
15517007	124	143	autoimmune diseases	Disease	D001327
15517007	171	189	systemic sclerosis	Disease	D012595
15517007	194	212	multiple sclerosis	Disease	D009103
15517007	342	361	autoimmune diseases	Disease	D001327
15517007	742	752	infections	Disease	D007239
15517007	786	802	cardiac toxicity	Disease	D066126
15517007	845	861	cyclophosphamide	Chemical	D003520
15517007	865	879	anthracyclines	Chemical	D018943
15517007	888	900	mitoxantrone	Chemical	D008942
15517007	949	961	heart damage	Disease	D006331
15517007	976	994	systemic sclerosis	Disease	D012595
15517007	1346	1364	autoimmune disease	Disease	D001327
15517007	CID	D008942	D006331
15517007	CID	D003520	D006331

12180796|t|Immunohistochemical study on inducible type of nitric oxide (iNOS), basic fibroblast growth factor (bFGF) and tumor growth factor-beta1 (TGF-beta1) in arteritis induced in rats by fenoldopam and theophylline, vasodilators.
12180796|a|Arteritis induced in rats by vasodilators, fenoldopam and theophylline, was examined immunohistochemically for expressions of inducible type of nitric oxide synthase (iNOS), basic fibroblast growth factor (bFGF) and tumor growth factor-beta1 (TGF-beta1). Rats were administered fenoldopam for 24 hours by intravenous infusion with or without following repeated daily oral administrations of theophylline. Irrespective of theophylline administration, iNOS antigens were remarkably abundant in ED-1-positive cells on day 5 and 8 post-fenoldopam-infusion (DPI); bFGF antigens were remarkably abundant in ED-1-positive cells on 1 and 3 DPI; TGF-beta1 antigens were observed in ED-1-positive cells on and after 5 DPI. These results suggest that the peak expression of iNOS antigen was followed by that of bFGF antigen, and bFGF may have a suppressive effect on iNOS expression in these rat arteritis models. On the other hand, TGF-beta1 was not considered to have a suppressive effect on iNOS expression in these models.
12180796	47	59	nitric oxide	Chemical	D009569
12180796	110	115	tumor	Disease	D009369
12180796	151	160	arteritis	Disease	D001167
12180796	180	190	fenoldopam	Chemical	D018818
12180796	195	207	theophylline	Chemical	D013806
12180796	223	232	Arteritis	Disease	D001167
12180796	266	276	fenoldopam	Chemical	D018818
12180796	281	293	theophylline	Chemical	D013806
12180796	367	379	nitric oxide	Chemical	D009569
12180796	439	444	tumor	Disease	D009369
12180796	501	511	fenoldopam	Chemical	D018818
12180796	614	626	theophylline	Chemical	D013806
12180796	644	656	theophylline	Chemical	D013806
12180796	755	765	fenoldopam	Chemical	D018818
12180796	1108	1117	arteritis	Disease	D001167
12180796	CID	D018818	D001167
12180796	CID	D013806	D001167

12109865|t|Low-molecular-weight heparin for the treatment of patients with mechanical heart valves.
12109865|a|BACKGROUND: The interruption of oral anticoagulant (OAC) administration is sometimes indicated in patients with mechanical heart valves, mainly before noncardiac surgery, non-surgical interventions, and pregnancy. Unfractionated heparin (UH) is currently the substitute for selected patients. Low-molecular-weight heparin (LMWH) offers theoretical advantages over UH, but is not currently considered in clinical guidelines as an alternative to UH in patients with prosthetic valves. HYPOTHESIS: The aim of the present study was to review the data accumulated so far on the use of LMWH in this patient population and to discuss its applicability in common practice. METHODS: For this paper, the current medical literature on LMWH in patients with mechanical heart valves was extensively reviewed. RESULTS: There were eight series and six case reports. None of the studies was randomized, and only one was prospective. Data to establish the thromboembolic risk were incomplete. After excluding case reports, the following groups were constructed: (a) short-term administration, after valve insertion (n = 212); (b) short-term, perioperative (noncardiac)/periprocedural (n = 114); (c) long-term, due to intolerance to OAC (n = 16); (d) long-term, in pregnancy (n = 10). The incidence rate of thromboembolism was 0.9% for all the studies and 0.5, 0, 20, and 0% in groups a, b, c, and d, respectively; for hemorrhage, the overall rate was 3.4% (3.8, 2.6, 10, and 0% for the respective groups). CONCLUSIONS: In patients with mechanical heart valves, short-term LMWH therapy compares favorably with UH. Data on mid- and long-term LMWH administration in these patients are sparse. Further randomized studies are needed to confirm the safety and precise indications for the use of LMWH in patients with mechanical heart valves.
12109865	0	28	Low-molecular-weight heparin	Chemical	D006495
12109865	303	325	Unfractionated heparin	Chemical	D006493
12109865	327	329	UH	Chemical	D006493
12109865	382	410	Low-molecular-weight heparin	Chemical	D006495
12109865	412	416	LMWH	Chemical	D006495
12109865	453	455	UH	Chemical	D006493
12109865	533	535	UH	Chemical	D006493
12109865	669	673	LMWH	Chemical	D006495
12109865	813	817	LMWH	Chemical	D006495
12109865	1028	1042	thromboembolic	Disease	D013923
12109865	1378	1393	thromboembolism	Disease	D013923
12109865	1490	1500	hemorrhage	Disease	D006470
12109865	1644	1648	LMWH	Chemical	D006495
12109865	1681	1683	UH	Chemical	D006493
12109865	1712	1716	LMWH	Chemical	D006495
12109865	1861	1865	LMWH	Chemical	D006495
12109865	CID	D006495	D006470
12109865	CID	D006495	D013923

12042105|t|Topiramate-induced nephrolithiasis.
12042105|a|Topiramate is a recently developed antiepileptic medication that is becoming more widely prescribed because of its efficacy in treating refractory seizures. Urologists should be aware that this medication can cause metabolic acidosis in patients secondary to inhibition of carbonic anhydrase. In addition, a distal tubular acidification defect may result, thus impairing the normal compensatory drop in urine pH. These factors can lead to the development of calcium phosphate nephrolithiasis. We report the first two cases of topiramate-induced nephrolithiasis in the urologic literature.
12042105	0	10	Topiramate	Chemical	C052342
12042105	19	34	nephrolithiasis	Disease	D053040
12042105	36	46	Topiramate	Chemical	C052342
12042105	172	191	refractory seizures	Disease	D004827
12042105	251	269	metabolic acidosis	Disease	D000138
12042105	494	511	calcium phosphate	Chemical	C020243
12042105	512	527	nephrolithiasis	Disease	D053040
12042105	562	572	topiramate	Chemical	C052342
12042105	581	596	nephrolithiasis	Disease	D053040
12042105	CID	C052342	D053040

11868798|t|Spironolactone: is it a novel drug for the prevention of amphotericin B-related hypokalemia in cancer patients?
11868798|a|OBJECTIVE: Nephrotoxicity is the major adverse effect of amphotericin B (AmB), often limiting administration of full dosage. Selective distal tubular epithelial toxicity seems to be responsible for the profound potassium wasting that is a major clinical side effect of treatment with AmB. Potassium depletion also potentiates the tubular toxicity of AmB. This study was designed to assess the ability of spironolactone to reduce potassium requirements and to prevent hypokalemia in neutropenic patients on AmB treatment. METHODS: In this study 26 patients with various hematological disorders were randomized to receive either intravenous AmB alone or AmB and oral spironolactone 100 mg twice daily when developing a proven or suspected fungal infection. RESULTS: Patients receiving concomitant AmB and spironolactone had significantly higher plasma potassium levels than those receiving AmB alone (P = 0.0027). Those patients receiving AmB and spironolactone required significantly less potassium supplementation to maintain their plasma potassium within the normal range (P = 0.022). Moreover, urinary potassium losses were significantly less in patients receiving AmB and spironolactone than those receiving AmB alone (P = 0.040). CONCLUSION: This study showed that spironolactone can reduce potassium requirements and prevent hypokalemia by reducing urinary potassium loss in neutropenic patients on AmB treatment.
11868798	0	14	Spironolactone	Chemical	D013148
11868798	57	71	amphotericin B	Chemical	D000666
11868798	80	91	hypokalemia	Disease	D007008
11868798	95	101	cancer	Disease	D009369
11868798	123	137	Nephrotoxicity	Disease	D007674
11868798	169	183	amphotericin B	Chemical	D000666
11868798	185	188	AmB	Chemical	D000666
11868798	273	281	toxicity	Disease	D064420
11868798	323	332	potassium	Chemical	D011188
11868798	396	399	AmB	Chemical	D000666
11868798	401	410	Potassium	Chemical	D011188
11868798	450	458	toxicity	Disease	D064420
11868798	462	465	AmB	Chemical	D000666
11868798	516	530	spironolactone	Chemical	D013148
11868798	541	550	potassium	Chemical	D011188
11868798	579	590	hypokalemia	Disease	D007008
11868798	594	605	neutropenic	Disease	D009503
11868798	618	621	AmB	Chemical	D000666
11868798	681	704	hematological disorders	Disease	D006402
11868798	751	754	AmB	Chemical	D000666
11868798	764	767	AmB	Chemical	D000666
11868798	777	791	spironolactone	Chemical	D013148
11868798	849	865	fungal infection	Disease	D009181
11868798	907	910	AmB	Chemical	D000666
11868798	915	929	spironolactone	Chemical	D013148
11868798	962	971	potassium	Chemical	D011188
11868798	1000	1003	AmB	Chemical	D000666
11868798	1049	1052	AmB	Chemical	D000666
11868798	1057	1071	spironolactone	Chemical	D013148
11868798	1100	1109	potassium	Chemical	D011188
11868798	1151	1160	potassium	Chemical	D011188
11868798	1216	1225	potassium	Chemical	D011188
11868798	1279	1282	AmB	Chemical	D000666
11868798	1287	1301	spironolactone	Chemical	D013148
11868798	1323	1326	AmB	Chemical	D000666
11868798	1381	1395	spironolactone	Chemical	D013148
11868798	1407	1416	potassium	Chemical	D011188
11868798	1442	1453	hypokalemia	Disease	D007008
11868798	1474	1483	potassium	Chemical	D011188
11868798	1492	1503	neutropenic	Disease	D009503
11868798	1516	1519	AmB	Chemical	D000666
11868798	CID	D000666	D007008

11860278|t|Dopamine D2 receptor signaling controls neuronal cell death induced by muscarinic and glutamatergic drugs.
11860278|a|Dopamine (DA), through D1/D2 receptor-mediated signaling, plays a major role in the control of epileptic seizures arising in the limbic system. Excitotoxicity leading to neuronal cell death in the affected areas is a major consequence of seizures at the cellular level. In this respect, little is known about the role of DA receptors in the occurrence of epilepsy-induced neuronal cell death. Here we analyze the occurrence of seizures and neurotoxicity in D2R -/- mice treated with the cholinergic agonist pilocarpine. We compared these results with those previously obtained with kainic acid (KA), a potent glutamate agonist. Importantly, D2R -/- mice develop seizures at doses of both drugs that are not epileptogenic for WT littermates and show greater neurotoxicity. However, pilocarpine-induced seizures result in a more widespread neuronal death in both WT and D2R -/- brains in comparison to KA. Thus, the absence of D2R lowers the threshold for seizures induced by both glutamate and acetylcholine. Moreover, the dopaminergic control of epilepsy-induced neurodegeneration seems to be mediated by distinct interactions of D2R signaling with these two neurotransmitters.
11860278	0	8	Dopamine	Chemical	D004298
11860278	107	115	Dopamine	Chemical	D004298
11860278	117	119	DA	Chemical	D004298
11860278	202	220	epileptic seizures	Disease	D004827
11860278	251	265	Excitotoxicity	Disease	-1
11860278	345	353	seizures	Disease	D012640
11860278	428	430	DA	Chemical	D004298
11860278	462	470	epilepsy	Disease	D004827
11860278	534	542	seizures	Disease	D012640
11860278	547	560	neurotoxicity	Disease	D020258
11860278	614	625	pilocarpine	Chemical	D010862
11860278	689	700	kainic acid	Chemical	D007608
11860278	702	704	KA	Chemical	D007608
11860278	716	725	glutamate	Chemical	D018698
11860278	769	777	seizures	Disease	D012640
11860278	864	877	neurotoxicity	Disease	D020258
11860278	888	899	pilocarpine	Chemical	D010862
11860278	908	916	seizures	Disease	D012640
11860278	1007	1009	KA	Chemical	D007608
11860278	1061	1069	seizures	Disease	D012640
11860278	1086	1095	glutamate	Chemical	D018698
11860278	1100	1113	acetylcholine	Chemical	D000109
11860278	1153	1161	epilepsy	Disease	D004827
11860278	1170	1187	neurodegeneration	Disease	D019636
11860278	CID	D010862	D012640
11860278	CID	D007608	D012640

11838826|t|Treatment of risperidone-induced hyperprolactinemia with a dopamine agonist in children.
11838826|a|BACKGROUND: Risperidone, a potent antagonist of both serotonergic (5HT2A) and dopaminergic D2 receptors is associated with hyperprolactinemia in adults and children. Chronically elevated prolactin levels in children with prolactinomas may be associated with arrested growth and development resulting in either delayed puberty or short stature. These possibilities stress the importance of developing a safe and effective approach to drug-induced hyperprolactinemia in youth. We report the successful treatment of risperidone-induced hyperprolactinemia with cabergoline in youth. METHODS: We undertook a retrospective case review of four children with risperidone-induced hyperprolactinemia treated with cabergoline. RESULTS: Four males (age 6-11 years) with Diagnostic and Statistical Manual of Mental Disorders (fourth edition) bipolar disorder or psychoses, with risperidone-induced elevations in serum prolactin levels (57.5-129 ng/mL, normal 5-15 ng/mL), were treated with cabergoline (mean dose 2.13 +/- 0.09 mg/week). When serum prolactin levels normalized in all four subjects (mean 11.2 +/- 10.9 ng/mL), the cabergoline dose was reduced to 1 mg/week in three of four subjects. The mean duration of therapy with cabergoline was 523.5 +/- 129.7 days, and the mean duration of therapy with risperidone was 788.5 +/- 162.5 days. Cabergoline was well tolerated without adverse effects. CONCLUSIONS: Cabergoline may be useful for the treatment of risperidone-induced hyperprolactinemia in youth; however, further research is needed.
11838826	13	24	risperidone	Chemical	D018967
11838826	33	51	hyperprolactinemia	Disease	D006966
11838826	59	67	dopamine	Chemical	D004298
11838826	101	112	Risperidone	Chemical	D018967
11838826	212	230	hyperprolactinemia	Disease	D006966
11838826	310	323	prolactinomas	Disease	D015175
11838826	399	414	delayed puberty	Disease	D011628
11838826	535	553	hyperprolactinemia	Disease	D006966
11838826	602	613	risperidone	Chemical	D018967
11838826	622	640	hyperprolactinemia	Disease	D006966
11838826	646	657	cabergoline	Chemical	C047047
11838826	740	751	risperidone	Chemical	D018967
11838826	760	778	hyperprolactinemia	Disease	D006966
11838826	792	803	cabergoline	Chemical	C047047
11838826	884	900	Mental Disorders	Disease	D001523
11838826	918	934	bipolar disorder	Disease	D001714
11838826	938	947	psychoses	Disease	D011605
11838826	954	965	risperidone	Chemical	D018967
11838826	1066	1077	cabergoline	Chemical	C047047
11838826	1205	1216	cabergoline	Chemical	C047047
11838826	1308	1319	cabergoline	Chemical	C047047
11838826	1384	1395	risperidone	Chemical	D018967
11838826	1422	1433	Cabergoline	Chemical	C047047
11838826	1491	1502	Cabergoline	Chemical	C047047
11838826	1538	1549	risperidone	Chemical	D018967
11838826	1558	1576	hyperprolactinemia	Disease	D006966
11838826	CID	D018967	D006966

11467664|t|Cholestatic jaundice associated with the use of metformin.
11467664|a|We report a patient who developed cholestatic jaundice shortly after initiation of treatment with metformin hydrochloride. Ultrasound of the liver and abdominal CT were normal. An ERCP showed normal biliary anatomy. A percutaneous liver biopsy was obtained showing marked cholestasis, with portal edema, ductular proliferation, and acute inflammation. Metformin hydrochloride was discontinued, and the patient's jaundice resolved slowly over a period of several months. Given the onset of his jaundice 2 wk after the initiation of metformin, we believe that this case represents an example of metformin-associated hepatotoxicity, the first such case reported.
11467664	0	20	Cholestatic jaundice	Disease	D041781
11467664	48	57	metformin	Chemical	D008687
11467664	93	113	cholestatic jaundice	Disease	D041781
11467664	157	180	metformin hydrochloride	Chemical	D008687
11467664	331	342	cholestasis	Disease	D002779
11467664	356	361	edema	Disease	D004487
11467664	397	409	inflammation	Disease	D007249
11467664	411	434	Metformin hydrochloride	Chemical	D008687
11467664	471	479	jaundice	Disease	D007565
11467664	552	560	jaundice	Disease	D007565
11467664	590	599	metformin	Chemical	D008687
11467664	652	661	metformin	Chemical	D008687
11467664	673	687	hepatotoxicity	Disease	D056486
11467664	CID	D008687	D041781
11467664	CID	D008687	D002779

11077455|t|Electro-oculography, electroretinography, visual evoked potentials, and multifocal electroretinography in patients with vigabatrin-attributed visual field constriction.
11077455|a|PURPOSE: Symptomatic visual field constriction thought to be associated with vigabatrin has been reported. The current study investigated the visual fields and visual electrophysiology of eight patients with known vigabatrin-attributed visual field loss, three of whom were reported previously. Six of the patients were no longer receiving vigabatrin. METHODS: The central and peripheral fields were examined with the Humphrey Visual Field Analyzer. Full visual electrophysiology, including flash electroretinography (ERG), pattern electroretinography, multifocal ERG using the VERIS system, electro-oculography, and flash and pattern visual evoked potentials, was undertaken. RESULTS: Seven patients showed marked visual field constriction with some sparing of the temporal visual field. The eighth exhibited concentric constriction. Most electrophysiological responses were usually just within normal limits; two patients had subnormal Arden electro-oculography indices; and one patient showed an abnormally delayed photopic b wave. However, five patients showed delayed 30-Hz flicker b waves, and seven patients showed delayed oscillatory potentials. Multifocal ERG showed abnormalities that sometimes correlated with the visual field appearance and confirmed that the deficit occurs at the retinal level. CONCLUSION: Marked visual field constriction appears to be associated with vigabatrin therapy. The field defects and some electrophysiological abnormalities persist when vigabatrin therapy is withdrawn.
11077455	120	130	vigabatrin	Chemical	D020888
11077455	142	167	visual field constriction	Disease	D014786
11077455	190	215	visual field constriction	Disease	D014786
11077455	246	256	vigabatrin	Chemical	D020888
11077455	383	393	vigabatrin	Chemical	D020888
11077455	405	422	visual field loss	Disease	D014786
11077455	509	519	vigabatrin	Chemical	D020888
11077455	884	909	visual field constriction	Disease	D014786
11077455	1497	1522	visual field constriction	Disease	D014786
11077455	1553	1563	vigabatrin	Chemical	D020888
11077455	1648	1658	vigabatrin	Chemical	D020888
11077455	CID	D020888	D014786

11063349|t|Conversion to rapamycin immunosuppression in renal transplant recipients: report of an initial experience.
11063349|a|BACKGROUND: The aim of this study is to evaluate the effects of RAPA conversion in patients undergoing cyclosporine (CsA) or tacrolimus (Tac) toxicity. METHODS: Twenty renal transplant recipients were switched to fixed dose rapamycin (RAPA) (5 mg/day) 0 to 204 months posttransplant. Drug monitoring was not initially used to adjust doses. The indications for switch were chronic CsA or Tac nephrotoxicity (12), acute CsA or Tac toxicity (3), severe facial dysmorphism (2), posttransplant lymphoproliferative disorder (PTLD) in remission (2), and hepatotoxicity in 1. Follow-up is 7 to 24 months. RESULTS: In the 12 patients switched because of chronic nephrotoxicity there was a significant decrease in serum creatinine [233+/-34 to 210+/-56 micromol/liter (P<0.05) at 6 months]. Facial dysmorphism improved in two patients. No relapse of PTLD was observed. Five patients developed pneumonia (two Pneumocystis carinii pneumonia, one infectious mononucleosis with polyclonal PTLD lung infiltrate) and two had bronchiolitis obliterans. There were no deaths. RAPA was discontinued in four patients, because of pneumonia in two, PTLD in one, and oral aphtous ulcers in one. RAPA levels were high (>15 ng/ml) in 7 of 13 (54%) patients. CONCLUSIONS: RAPA conversion provides adequate immunosuppression to enable CsA withdrawal. However, when converting patients to RAPA drug levels should be monitored to avoid over-immunosuppression and adequate antiviral and Pneumocystis carinii pneumonia prophylaxis should be given.
11063349	14	23	rapamycin	Chemical	D020123
11063349	171	175	RAPA	Chemical	D020123
11063349	210	222	cyclosporine	Chemical	D016572
11063349	224	227	CsA	Chemical	D016572
11063349	232	242	tacrolimus	Chemical	D016559
11063349	244	247	Tac	Chemical	D016559
11063349	249	257	toxicity	Disease	D064420
11063349	331	340	rapamycin	Chemical	D020123
11063349	342	346	RAPA	Chemical	D020123
11063349	487	490	CsA	Chemical	D016572
11063349	494	497	Tac	Chemical	D016559
11063349	498	512	nephrotoxicity	Disease	D007674
11063349	525	528	CsA	Chemical	D016572
11063349	532	535	Tac	Chemical	D016559
11063349	536	544	toxicity	Disease	D064420
11063349	557	575	facial dysmorphism	Disease	-1
11063349	581	624	posttransplant lymphoproliferative disorder	Disease	D008232
11063349	626	630	PTLD	Disease	D008232
11063349	654	668	hepatotoxicity	Disease	D056486
11063349	760	774	nephrotoxicity	Disease	D007674
11063349	817	827	creatinine	Chemical	D003404
11063349	888	906	Facial dysmorphism	Disease	-1
11063349	947	951	PTLD	Disease	D008232
11063349	990	999	pneumonia	Disease	D011014
11063349	1005	1035	Pneumocystis carinii pneumonia	Disease	D011020
11063349	1041	1065	infectious mononucleosis	Disease	D007244
11063349	1082	1086	PTLD	Disease	D008232
11063349	1116	1140	bronchiolitis obliterans	Disease	D001989
11063349	1164	1168	RAPA	Chemical	D020123
11063349	1215	1224	pneumonia	Disease	D011014
11063349	1233	1237	PTLD	Disease	D008232
11063349	1255	1269	aphtous ulcers	Disease	D013281
11063349	1278	1282	RAPA	Chemical	D020123
11063349	1352	1356	RAPA	Chemical	D020123
11063349	1414	1417	CsA	Chemical	D016572
11063349	1467	1471	RAPA	Chemical	D020123
11063349	1563	1593	Pneumocystis carinii pneumonia	Disease	D011020
11063349	CID	D016559	D007674
11063349	CID	D016572	D007674

10091616|t|Worsening of levodopa-induced dyskinesias by motor and mental tasks.
10091616|a|Ten patients who had Parkinson's disease with disabling dyskinesia were included in this study to evaluate the role of mental (mental calculation) and motor (flexion/extension of right fingers, flexion/extension of left fingers, flexion/extension of the neck, speaking aloud) tasks on the worsening of peak-dose dyskinesia following administration of an effective single dose of apomorphine. Compared with the score at rest (1.3+/-0.3), a significant aggravation of the dyskinesia score was observed during speaking aloud (5.2+/-1.1, p<0.05), movements of right (4.5+/-1.0, p<0.05) and left (3.7+/-0.8, p<0.05) fingers, movements of the neck (5.1+/-1.0, p<0.05), and mental calculation (3.1+/-1.0, p<0.05). These results suggest that activation tasks such as "speaking aloud" could be used for objective assessment of dyskinesia severity.
10091616	13	21	levodopa	Chemical	D007980
10091616	30	41	dyskinesias	Disease	D004409
10091616	90	109	Parkinson's disease	Disease	D010300
10091616	125	135	dyskinesia	Disease	D004409
10091616	381	391	dyskinesia	Disease	D004409
10091616	448	459	apomorphine	Chemical	D001058
10091616	539	549	dyskinesia	Disease	D004409
10091616	887	897	dyskinesia	Disease	D004409
10091616	CID	D001058	D004409
10091616	CID	D007980	D004409

9952311|t|Structural and functional impairment of mitochondria in adriamycin-induced cardiomyopathy in mice: suppression of cytochrome c oxidase II gene expression.
9952311|a|The use of adriamycin (ADR) in cancer chemotherapy has been limited due to its cumulative cardiovascular toxicity. Earlier observations that ADR interacts with mitochondrial cytochrome c oxidase (COX) and suppresses its enzyme activity led us to investigate ADR's action on the cardiovascular functions and heart mitochondrial morphology in Balb-c mice i.p. treated with ADR for several weeks. At various times during treatment, the animals were assessed for cardiovascular functions by electrocardiography and for heart tissue damage by electron microscopy. In parallel, total RNA was extracted from samples of dissected heart and analyzed by Northern blot hybridization to determine the steady-state level of three RNA transcripts encoded by the COXII, COXIII, and COXIV genes. Similarly, samples obtained from the liver of the same animals were analyzed for comparative studies. Our results indicated that 1) treatment of mice with ADR caused cardiovascular arrhythmias characterized by bradycardia, extension of ventricular depolarization time (tQRS), and failure of QRS at high concentrations (10-14 mg/kg body weight cumulative dose); 2) the heart mitochondria underwent swelling, fusion, dissolution, and/or disruption of mitochondrial cristae after several weeks of treatment. Such abnormalities were not observed in the mitochondria of liver tissue; and 3) among the three genes of COX enzyme examined, only COXII gene expression was suppressed by ADR treatment, mainly after 8 weeks in both heart and liver. Knowing that heart mitochondria represent almost 40% of heart muscle by weight, we conclude that the deteriorating effects of ADR on cardiovascular function involve mitochondrial structural and functional impairment.
9952311	0	52	Structural and functional impairment of mitochondria	Disease	D028361
9952311	56	66	adriamycin	Chemical	D004317
9952311	75	89	cardiomyopathy	Disease	D009202
9952311	166	176	adriamycin	Chemical	D004317
9952311	178	181	ADR	Chemical	D004317
9952311	186	192	cancer	Disease	D009369
9952311	245	268	cardiovascular toxicity	Disease	D002318
9952311	296	299	ADR	Chemical	D004317
9952311	413	416	ADR	Chemical	D004317
9952311	526	529	ADR	Chemical	D004317
9952311	1090	1093	ADR	Chemical	D004317
9952311	1101	1127	cardiovascular arrhythmias	Disease	D001145
9952311	1145	1156	bradycardia	Disease	D001919
9952311	1332	1340	swelling	Disease	D004487
9952311	1612	1615	ADR	Chemical	D004317
9952311	1799	1802	ADR	Chemical	D004317
9952311	1838	1888	mitochondrial structural and functional impairment	Disease	D028361
9952311	CID	D004317	D028361
9952311	CID	D004317	D001919

9915601|t|Enhanced bradycardia induced by beta-adrenoceptor antagonists in rats pretreated with isoniazid.
9915601|a|High doses of isoniazid increase hypotension induced by vasodilators and change the accompanying reflex tachycardia to bradycardia, an interaction attributed to decreased synthesis of brain gamma-aminobutyric acid (GABA). In the present study, the possible enhancement by isoniazid of bradycardia induced by beta-adrenoceptor antagonists was determined in rats anaesthetised with chloralose-urethane. Isoniazid significantly increased bradycardia after propranolol, pindolol, labetalol and atenolol, as well as after clonidine, but not after hexamethonium or carbachol. Enhancement was not observed in rats pretreated with methylatropine or previously vagotomised. These results are compatible with interference by isoniazid with GABAergic inhibition of cardiac parasympathetic tone. Such interference could be exerted centrally, possibly at the nucleus ambiguus, or peripherally at the sinus node.
9915601	9	20	bradycardia	Disease	D001919
9915601	86	95	isoniazid	Chemical	D007538
9915601	111	120	isoniazid	Chemical	D007538
9915601	130	141	hypotension	Disease	D007022
9915601	201	212	tachycardia	Disease	D013610
9915601	216	227	bradycardia	Disease	D001919
9915601	287	310	gamma-aminobutyric acid	Chemical	D005680
9915601	312	316	GABA	Chemical	D005680
9915601	369	378	isoniazid	Chemical	D007538
9915601	382	393	bradycardia	Disease	D001919
9915601	477	487	chloralose	Chemical	D002698
9915601	488	496	urethane	Chemical	D014520
9915601	498	507	Isoniazid	Chemical	D007538
9915601	532	543	bradycardia	Disease	D001919
9915601	550	561	propranolol	Chemical	D011433
9915601	563	571	pindolol	Chemical	D010869
9915601	573	582	labetalol	Chemical	D007741
9915601	587	595	atenolol	Chemical	D001262
9915601	614	623	clonidine	Chemical	D003000
9915601	639	652	hexamethonium	Chemical	D018738
9915601	656	665	carbachol	Chemical	D002217
9915601	720	734	methylatropine	Chemical	C006649
9915601	812	821	isoniazid	Chemical	D007538
9915601	CID	D007538	D001919
9915601	CID	D007538	D007022

9758264|t|Epileptogenic activity of folic acid after drug induces SLE (folic acid and epilepsy)
9758264|a|OBJECTIVE: To study the effect of folic acid-containing multivitamin supplementation in epileptic women before and during pregnancy in order to determine the rate of structural birth defects and epilepsy-related side effects. STUDY DESIGN: First a randomised trial, later periconception care including in total 12225 females. RESULTS: Of 60 epileptic women with periconceptional folic acid (0.8 mg)-containing multivitamin supplementation, no one developed epilepsy-related side effects during the periconception period. One epileptic woman delivered a newborn with cleft lip and palate. Another patient exhibited with a cluster of seizures after the periconception period using another multivitamin. This 22-year-old epileptic woman was treated continuously by carbamazepine and a folic acid (1 mg)-containing multivitamin from the 20th week of gestation. She developed status epilepticus and later symptoms of systemic lupus erythematodes. Her pregnancy ended with stillbirth. CONCLUSIONS: The epileptic pregnant patient's autoimmune disease (probably drug-induced lupus) could damage the blood-brain barrier, therefore the therapeutic dose (> or =1 mg) of folic acid triggered a cluster of seizures. Physiological dose (<1 mg) of folic acid both in healthy and 60 epileptic women, all without any autoimmune disease, did not increase the risk for epileptic seizures.
9758264	26	36	folic acid	Chemical	D005492
9758264	56	59	SLE	Disease	D008180
9758264	61	71	folic acid	Chemical	D005492
9758264	76	84	epilepsy	Disease	D004827
9758264	120	130	folic acid	Chemical	D005492
9758264	174	183	epileptic	Disease	D004827
9758264	263	276	birth defects	Disease	D000014
9758264	281	289	epilepsy	Disease	D004827
9758264	427	436	epileptic	Disease	D004827
9758264	465	475	folic acid	Chemical	D005492
9758264	543	551	epilepsy	Disease	D004827
9758264	611	620	epileptic	Disease	D004827
9758264	652	672	cleft lip and palate	Disease	D002971|D002972	cleft lip|cleft palate
9758264	718	726	seizures	Disease	D012640
9758264	804	813	epileptic	Disease	D004827
9758264	848	861	carbamazepine	Chemical	D002220
9758264	868	878	folic acid	Chemical	D005492
9758264	957	975	status epilepticus	Disease	D013226
9758264	998	1026	systemic lupus erythematodes	Disease	D008180
9758264	1053	1063	stillbirth	Disease	D050497
9758264	1082	1091	epileptic	Disease	D004827
9758264	1111	1129	autoimmune disease	Disease	D001327
9758264	1153	1158	lupus	Disease	D008180
9758264	1245	1255	folic acid	Chemical	D005492
9758264	1279	1287	seizures	Disease	D012640
9758264	1319	1329	folic acid	Chemical	D005492
9758264	1353	1362	epileptic	Disease	D004827
9758264	1386	1404	autoimmune disease	Disease	D001327
9758264	1436	1454	epileptic seizures	Disease	D004827
9758264	CID	D005492	D012640
9758264	CID	D005492	D008180

9669632|t|Effects of cisapride on symptoms and postcibal small-bowel motor function in patients with irritable bowel syndrome.
9669632|a|BACKGROUND: Irritable bowel syndrome is a common cause of abdominal pain and discomfort and may be related to disordered gastrointestinal motility. Our aim was to assess the effects of long-term treatment with a prokinetic agent, cisapride, on postprandial jejunal motility and symptoms in the irritable bowel syndrome (IBS). METHODS: Thirty-eight patients with IBS (constipation-predominant, n = 17; diarrhoea-predominant, n = 21) underwent 24-h ambulatory jejunal manometry before and after 12 week's treatment [cisapride, 5 mg three times daily (n = 19) or placebo (n = 19)]. RESULTS: In diarrhoea-predominant patients significant differences in contraction characteristics were observed between the cisapride and placebo groups. In cisapride-treated diarrhoea-predominant patients the mean contraction amplitude was higher (29.3 +/- 3.2 versus 24.9 +/- 2.6 mm Hg, cisapride versus placebo (P < 0.001); pretreatment, 25.7 +/- 6.0 mm Hg), the mean contraction duration longer (3.4 +/- 0.2 versus 3.0 +/- 0.2 sec, cisapride versus placebo (P < 0.001); pretreatment, 3.1 +/- 0.5 sec), and the mean contraction frequency lower (2.0 +/- 0.2 versus 2.5 +/- 0.4 cont./min, cisapride versus placebo (P < 0.001); pretreatment, 2.5 +/- 1.1 cont./min] than patients treated with placebo. No significant differences in jejunal motility were found in the constipation-predominant IBS group. Symptoms were assessed by using a visual analogue scale before and after treatment. Symptom scores relating to the severity of constipation were lower in cisapride-treated constipation-predominant IBS patients [score, 54 +/- 5 versus 67 +/- 14 mm, cisapride versus placebo (P < 0.05); pretreatment, 62 +/- 19 mm]. Diarrhoea-predominant IBS patients had a higher pain score after cisapride therapy [score, 55 +/- 15 versus 34 +/- 12 mm, cisapride versus placebo (P < 0.05); pretreatment, 67 +/- 19 mm]. CONCLUSION: Cisapride affects jejunal contraction characteristics and some symptoms in IBS.
9669632	11	20	cisapride	Chemical	D020117
9669632	91	115	irritable bowel syndrome	Disease	D043183
9669632	129	153	Irritable bowel syndrome	Disease	D043183
9669632	175	189	abdominal pain	Disease	D015746
9669632	227	263	disordered gastrointestinal motility	Disease	D005767
9669632	347	356	cisapride	Chemical	D020117
9669632	411	435	irritable bowel syndrome	Disease	D043183
9669632	437	440	IBS	Disease	D043183
9669632	479	482	IBS	Disease	D043183
9669632	484	496	constipation	Disease	D003248
9669632	518	527	diarrhoea	Disease	D003967
9669632	631	640	cisapride	Chemical	D020117
9669632	708	717	diarrhoea	Disease	D003967
9669632	820	829	cisapride	Chemical	D020117
9669632	853	862	cisapride	Chemical	D020117
9669632	871	880	diarrhoea	Disease	D003967
9669632	985	994	cisapride	Chemical	D020117
9669632	1132	1141	cisapride	Chemical	D020117
9669632	1286	1295	cisapride	Chemical	D020117
9669632	1462	1474	constipation	Disease	D003248
9669632	1487	1490	IBS	Disease	D043183
9669632	1625	1637	constipation	Disease	D003248
9669632	1652	1661	cisapride	Chemical	D020117
9669632	1670	1682	constipation	Disease	D003248
9669632	1695	1698	IBS	Disease	D043183
9669632	1746	1755	cisapride	Chemical	D020117
9669632	1812	1821	Diarrhoea	Disease	D003967
9669632	1834	1837	IBS	Disease	D043183
9669632	1860	1864	pain	Disease	D010146
9669632	1877	1886	cisapride	Chemical	D020117
9669632	1934	1943	cisapride	Chemical	D020117
9669632	2012	2021	Cisapride	Chemical	D020117
9669632	2087	2090	IBS	Disease	D043183
9669632	CID	D020117	D015746

9326871|t|Clarithromycin-induced ventricular tachycardia.
9326871|a|Clarithromycin is a relatively new macrolide antibiotic that offers twice-daily dosing. It differs from erythromycin only in the methylation of the hydroxyl group at position 6. Although the side-effect profile of erythromycin is established, including gastroenteritis and interactions with other drugs subject to hepatic mixed-function oxidase metabolism, experience with the newer macrolides is still being recorded. Cardiotoxicity has been demonstrated after both intravenous and oral administration of erythromycin but has never been reported with the newer macrolides. We report a case of ventricular dysrhythmias that occurred after six therapeutic doses of clarithromycin. The dysrhythmias resolved after discontinuation of the drug.
9326871	0	14	Clarithromycin	Chemical	D017291
9326871	23	46	ventricular tachycardia	Disease	D017180
9326871	48	62	Clarithromycin	Chemical	D017291
9326871	83	92	macrolide	Chemical	D018942
9326871	152	164	erythromycin	Chemical	D004917
9326871	262	274	erythromycin	Chemical	D004917
9326871	301	316	gastroenteritis	Disease	D005759
9326871	431	441	macrolides	Chemical	D018942
9326871	467	481	Cardiotoxicity	Disease	D066126
9326871	554	566	erythromycin	Chemical	D004917
9326871	610	620	macrolides	Chemical	D018942
9326871	642	666	ventricular dysrhythmias	Disease	D001145
9326871	712	726	clarithromycin	Chemical	D017291
9326871	732	744	dysrhythmias	Disease	D001145
9326871	CID	D004917	D005759
9326871	CID	D017291	D017180

9226773|t|Persistent nephrogenic diabetes insipidus following lithium therapy.
9226773|a|We report the case of a patient who developed severe hypernatraemic dehydration following a head injury. Ten years previously he had been diagnosed to have lithium-induced nephrogenic diabetes insipidus, and lithium therapy had been discontinued. He remained thirsty and polyuric despite cessation of lithium and investigations on admission showed him to have normal osmoregulated thirst and vasopressin secretion, with clear evidence of nephrogenic diabetes insipidus. Lithium induced nephrogenic diabetes insipidus is considered to be reversible on cessation of therapy but polyuria persisted in this patient for ten years after lithium was stopped. We discuss the possible renal mechanisms and the implications for management of patients with lithium-induced nephrogenic diabetes insipidus.
9226773	11	41	nephrogenic diabetes insipidus	Disease	D018500
9226773	52	59	lithium	Chemical	D008094
9226773	137	148	dehydration	Disease	D003681
9226773	161	172	head injury	Disease	D006259
9226773	225	232	lithium	Chemical	D008094
9226773	241	271	nephrogenic diabetes insipidus	Disease	D018500
9226773	277	284	lithium	Chemical	D008094
9226773	340	348	polyuric	Disease	D011141
9226773	370	377	lithium	Chemical	D008094
9226773	461	472	vasopressin	Chemical	D014667
9226773	507	537	nephrogenic diabetes insipidus	Disease	D018500
9226773	539	546	Lithium	Chemical	D008094
9226773	555	585	nephrogenic diabetes insipidus	Disease	D018500
9226773	645	653	polyuria	Disease	D011141
9226773	700	707	lithium	Chemical	D008094
9226773	815	822	lithium	Chemical	D008094
9226773	831	861	nephrogenic diabetes insipidus	Disease	D018500
9226773	CID	D008094	D018500
9226773	CID	D008094	D011141

8600333|t|Late cardiotoxicity after treatment for a malignant bone tumor.
8600333|a|Cardiac function was assessed in long-term survivors of malignant bone tumors who were treated according to Rosen's T5 or T10 protocol, both including doxorubicin. Thirty-one patients, age 10-45 years (median age 17.8 years) were evaluated 2.3-14.1 years (median 8.9 years) following completion of treatment. Cumulative doses of doxorubicin were 225-550 mg/m2 (median dose 360). The evaluation consisted of a history, physical examination, electrocardiogram (ECG), signal averaged ECG, 24-hour ambulatory ECG, echocardiography and radionuclide angiography. Eighteen of 31 (58%) patients showed cardiac toxicity, defined as having one or more of the following abnormalities: late potentials, complex ventricular arrhythmias, left ventricular dilation, decreased shortening fraction, or decreased ejection fraction. The incidence of cardiac abnormalities increased with length of follow-up (P< or = .05). No correlation could be demonstrated between cumulative dose of doxorubicin and cardiac status, except for heart rate variability. When adjusted to body surface area, the left ventricular posterior wall thickness (LVPW index) was decreased in all patients. The incidence of doxorubicin-induced cardiotoxicity is high and increases with follow-up, irrespective of cumulative dose. Life-long cardiac follow-up in these patients is warranted. The results of our study suggest that heart rate variability and LVPW index could be sensitive indicators for cardiotoxicity.
8600333	5	19	cardiotoxicity	Disease	D066126
8600333	52	62	bone tumor	Disease	D001859
8600333	130	141	bone tumors	Disease	D001859
8600333	172	198	Rosen's T5 or T10 protocol	Chemical	C053519
8600333	215	226	doxorubicin	Chemical	D004317
8600333	393	404	doxorubicin	Chemical	D004317
8600333	658	674	cardiac toxicity	Disease	D066126
8600333	763	786	ventricular arrhythmias	Disease	D001145
8600333	793	813	ventricular dilation	Disease	D002311
8600333	895	916	cardiac abnormalities	Disease	D006331
8600333	1031	1042	doxorubicin	Chemical	D004317
8600333	1241	1252	doxorubicin	Chemical	D004317
8600333	1261	1275	cardiotoxicity	Disease	D066126
8600333	1517	1531	cardiotoxicity	Disease	D066126
8600333	CID	D004317	D006331

8514073|t|Venous complications of midazolam versus diazepam.
8514073|a|Although some studies have suggested fewer venous complications are associated with midazolam than with diazepam for endoscopic procedures, this variable has not been well documented. We prospectively evaluated the incidence of venous complications after intravenous injection of diazepam or midazolam in 122 consecutive patients undergoing colonoscopy and esophagogastroduodenoscopy. Overall, venous complications were more frequent with diazepam (22 of 62 patients) than with midazolam (4 of 60 patients) (p < 0.001). A palpable venous cord was present in 23% (14 of 62) of patients in the diazepam group, compared with 2% (1 of 60 patients) in the midazolam group (p < 0.002). Pain at the injection site occurred in 35% (22 of 62) of patients in the diazepam group compared with 7% (4 of 60 patients) in the midazolam group (p < 0.001). Swelling and warmth at the injection site were not significantly different between the two groups. Smoking, nonsteroidal anti-inflammatory drug use, intravenous catheter site, dwell time of the needle, alcohol use, and pain during the injection had no effect on the incidence of venous complications.
8514073	0	20	Venous complications	Disease	D014652
8514073	24	33	midazolam	Chemical	D008874
8514073	41	49	diazepam	Chemical	D003975
8514073	94	114	venous complications	Disease	D014652
8514073	135	144	midazolam	Chemical	D008874
8514073	155	163	diazepam	Chemical	D003975
8514073	279	299	venous complications	Disease	D014652
8514073	331	339	diazepam	Chemical	D003975
8514073	343	352	midazolam	Chemical	D008874
8514073	445	465	venous complications	Disease	D014652
8514073	490	498	diazepam	Chemical	D003975
8514073	529	538	midazolam	Chemical	D008874
8514073	643	651	diazepam	Chemical	D003975
8514073	702	711	midazolam	Chemical	D008874
8514073	731	735	Pain	Disease	D010146
8514073	804	812	diazepam	Chemical	D003975
8514073	862	871	midazolam	Chemical	D008874
8514073	891	899	Swelling	Disease	D004487
8514073	1093	1100	alcohol	Chemical	D000431
8514073	1110	1114	pain	Disease	D010146
8514073	1170	1190	venous complications	Disease	D014652
8514073	CID	D003975	D014652
8514073	CID	D008874	D014652

8492347|t|Tetany and rhabdomyolysis due to surreptitious furosemide--importance of magnesium supplementation.
8492347|a|Diuretics may induce hypokalemia, hypocalcemia and hypomagnesemia. While severe hypokalemia may cause muscle weakness, severe hypomagnesemia is associated with muscle spasms and tetany which cannot be corrected by potassium and calcium supplementation alone (1,2). Surreptitious diuretic ingestion has been described, mainly in women who are concerned that they are obese or edematous. Symptomatic hypokalemia has been reported in such patients (3-7) and in one case hypocalcemia was observed (8), but the effects of magnesium depletion were not noted in these patients.
8492347	0	6	Tetany	Disease	D013746
8492347	11	25	rhabdomyolysis	Disease	D012206
8492347	47	57	furosemide	Chemical	D005665
8492347	73	82	magnesium	Chemical	D008274
8492347	121	132	hypokalemia	Disease	D007008
8492347	134	146	hypocalcemia	Disease	D006996
8492347	151	165	hypomagnesemia	Disease	C537153
8492347	180	191	hypokalemia	Disease	D007008
8492347	202	217	muscle weakness	Disease	D018908
8492347	226	240	hypomagnesemia	Disease	C537153
8492347	260	273	muscle spasms	Disease	D013035
8492347	278	284	tetany	Disease	D013746
8492347	314	323	potassium	Chemical	D011188
8492347	328	335	calcium	Chemical	D002118
8492347	466	471	obese	Disease	D009765
8492347	475	484	edematous	Disease	D004487
8492347	498	509	hypokalemia	Disease	D007008
8492347	567	579	hypocalcemia	Disease	D006996
8492347	617	626	magnesium	Chemical	D008274
8492347	CID	D005665	D012206
8492347	CID	D005665	D013746

8410199|t|Loss of glutamate decarboxylase mRNA-containing neurons in the rat dentate gyrus following pilocarpine-induced seizures.
8410199|a|In situ hybridization methods were used to determine if glutamic acid decarboxylase (GAD) mRNA-containing neurons within the hilus of the dentate gyrus are vulnerable to seizure-induced damage in a model of chronic seizures. Sprague-Dawley rats were injected intraperitoneally with pilocarpine, and the hippocampal formation was studied histologically at 1, 2, 4, and 8 week intervals after pilocarpine-induced seizures. In situ hybridization histochemistry, using a digoxigenin-labeled GAD cRNA probe, demonstrated a substantial decrease in the number of GAD mRNA-containing neurons in the hilus of the dentate gyrus in the pilocarpine-treated rats as compared to controls at all time intervals. Additional neuronanatomical studies, including cresyl violet staining, neuronal degeneration methods, and histochemical localization of glial fibrillary acidic protein, suggested that the decrease in the number of GAD mRNA-containing neurons was related to neuronal loss rather than to a decrease in GAD mRNA levels. The loss of GAD mRNA-containing neurons in the hilus contrasted with the relative preservation of labeled putative basket cells along the inner margin of the granule cell layer. Quantitative analyses of labeled neurons in three regions of the dentate gyrus in the 1 and 2 week groups showed statistically significant decreases in the mean number of GAD mRNA-containing neurons in the hilus of both groups of experimental animals. No significant differences were found in the molecular layer or the granule cell layer, which included labeled neurons along the lower margin of the granule cell layer. The results indicate that, in this model, a subpopulation of GAD mRNA-containing neurons within the dentate gyrus is selectively vulnerable to seizure-induced damage. Such differential vulnerability appears to be another indication of the heterogeneity of GABA neurons.
8410199	8	17	glutamate	Chemical	D018698
8410199	91	102	pilocarpine	Chemical	D010862
8410199	111	119	seizures	Disease	D012640
8410199	177	190	glutamic acid	Chemical	D018698
8410199	291	298	seizure	Disease	D012640
8410199	336	344	seizures	Disease	D012640
8410199	403	414	pilocarpine	Chemical	D010862
8410199	512	523	pilocarpine	Chemical	D010862
8410199	532	540	seizures	Disease	D012640
8410199	588	599	digoxigenin	Chemical	D004076
8410199	746	757	pilocarpine	Chemical	D010862
8410199	865	878	cresyl violet	Chemical	C028911
8410199	889	910	neuronal degeneration	Disease	D009410
8410199	1075	1088	neuronal loss	Disease	D009410
8410199	1877	1884	seizure	Disease	D012640
8410199	1990	1994	GABA	Chemical	D005680
8410199	CID	D010862	D012640
8410199	CID	D010862	D009410

7791169|t|Protective effect of misoprostol on indomethacin induced renal dysfunction in elderly patients.
7791169|a|OBJECTIVE: To evaluate the possible protective effects of misoprostol on renal function in hospitalized elderly patients treated with indomethacin. METHODS: Forty-five hospitalized elderly patients (> 65 years old) who required therapy with nonsteroidal antiinflammatory drugs (NSAID) were randomly assigned to receive either indomethacin, 150 mg/day (Group A), or indomethacin 150 mg/day plus misoprostol at 0.6 mg/day (Group B). Laboratory variables of renal function [serum creatinine, blood urea nitrogen (BUN) and electrolytes] were evaluated before initiation of therapy and every 2 days, until termination of the study (a period of at least 6 days). Response to treatment was estimated by the visual analog scale for severity of pain. RESULTS: Forty-two patients completed the study, 22 in Group A and 20 in Group B. BUN and creatinine increased by > 50% of baseline levels in 54 and 45% of Group A patients, respectively, compared to only 20 and 10% of Group B patients (p < 0.05). Potassium (K) increment of 0.6 mEq/l or more was observed in 50% of Group A, but in only 15% of Group B patients (p < 0.05). The mean increments in BUN, creatinine, and K were reduced by 63, 80, and 42%, respectively, in Group B patients compared to Group A. Response to treatment did not differ significantly between the 2 groups. CONCLUSION: Hospitalized elderly patients are at risk for developing indomethacin related renal dysfunction. Addition of misoprostol can minimize this renal impairment without affecting pain control.
7791169	21	32	misoprostol	Chemical	D016595
7791169	36	48	indomethacin	Chemical	D007213
7791169	57	74	renal dysfunction	Disease	D007674
7791169	154	165	misoprostol	Chemical	D016595
7791169	230	242	indomethacin	Chemical	D007213
7791169	422	434	indomethacin	Chemical	D007213
7791169	461	473	indomethacin	Chemical	D007213
7791169	490	501	misoprostol	Chemical	D016595
7791169	573	583	creatinine	Chemical	D003404
7791169	585	604	blood urea nitrogen	Chemical	D001806
7791169	606	609	BUN	Chemical	D001806
7791169	832	836	pain	Disease	D010146
7791169	920	923	BUN	Chemical	D001806
7791169	928	938	creatinine	Chemical	D003404
7791169	1086	1095	Potassium	Chemical	D011188
7791169	1097	1098	K	Chemical	D011188
7791169	1234	1237	BUN	Chemical	D001806
7791169	1239	1249	creatinine	Chemical	D003404
7791169	1255	1256	K	Chemical	D011188
7791169	1487	1499	indomethacin	Chemical	D007213
7791169	1508	1525	renal dysfunction	Disease	D007674
7791169	1539	1550	misoprostol	Chemical	D016595
7791169	1569	1585	renal impairment	Disease	D007674
7791169	1604	1608	pain	Disease	D010146
7791169	CID	D007213	D007674

6728084|t|Nephrotoxic effects of aminoglycoside treatment on renal protein reabsorption and accumulation.
6728084|a|To quantify the effects of gentamicin, kanamycin and netilmicin on renal protein reabsorption and accumulation, these drugs were administered to rats intraperitoneally (30 mg/kg/day) for 7, 14 or 21 days. Scanning electron microscopy of the glomerular endothelia, urinary measurements of sodium, potassium, endogenous lysozyme, N-acetyl-beta-D-glucosaminidase (NAG) as well as clearance and accumulation experiments after i.v. administration of egg-white lysozyme and measurements of inulin clearance (GFR) were done in each treatment group. Gentamicin administration decreased diameter, density and shape of endothelial fenestrae. Kanamycin and netilmicin appeared to have no effect at the dose used. All three aminoglycosides decreased GFR and increased urinary excretion of sodium and potassium. While gentamicin and kanamycin decreased the percentage reabsorption and accumulation of lysozyme after i.v. administration of egg-white lysozyme netilmicin had no effect. Daily excretion of total protein, endogenous lysozyme and NAG increased only after treatment with kanamycin and gentamicin. Thus, aminoglycosides may act as nephrotoxicants at glomerular and/or tubular level inducing impairment of renal reabsorption and accumulation of proteins.
6728084	0	11	Nephrotoxic	Disease	D007674
6728084	23	37	aminoglycoside	Chemical	D000617
6728084	123	133	gentamicin	Chemical	D005839
6728084	135	144	kanamycin	Chemical	D007612
6728084	149	159	netilmicin	Chemical	D009428
6728084	384	390	sodium	Chemical	D012964
6728084	392	401	potassium	Chemical	D011188
6728084	638	648	Gentamicin	Chemical	D005839
6728084	728	737	Kanamycin	Chemical	D007612
6728084	742	752	netilmicin	Chemical	D009428
6728084	808	823	aminoglycosides	Chemical	D000617
6728084	873	879	sodium	Chemical	D012964
6728084	884	893	potassium	Chemical	D011188
6728084	901	911	gentamicin	Chemical	D005839
6728084	916	925	kanamycin	Chemical	D007612
6728084	1041	1051	netilmicin	Chemical	D009428
6728084	1165	1174	kanamycin	Chemical	D007612
6728084	1179	1189	gentamicin	Chemical	D005839
6728084	1197	1212	aminoglycosides	Chemical	D000617
6728084	1284	1316	impairment of renal reabsorption	Disease	D007674
6728084	CID	D007612	D007674
6728084	CID	D005839	D007674

6111982|t|Pharmacology of GYKI-41 099 (chlorpropanol, Tobanum) a new potent beta-adrenergic antagonist.
6111982|a|The compound GYKI-41 099, as a beta-adrenergic antagonist, is 3-8 times more potent than propranolol in vitro and in vivo. Its antiarrhythmic effectiveness surpasses that of propranolol and pindolol inhibiting the ouabain arrhythmia in dogs and cats. GYKI-41 900 has a negligible cardiodepressant activity; it is not cardioselective. The compound shows a rapid and long lasting effect. There was a prolonged elimination of the radioactivity after the injection of 14C-41 099 to rats and dogs. The half life of the unlabeled substance in humans was more than 10 hours.
6111982	16	27	GYKI-41 099	Chemical	C025725
6111982	29	42	chlorpropanol	Chemical	C025725
6111982	44	51	Tobanum	Chemical	C025725
6111982	107	118	GYKI-41 099	Chemical	C025725
6111982	183	194	propranolol	Chemical	D011433
6111982	268	279	propranolol	Chemical	D011433
6111982	284	292	pindolol	Chemical	D010869
6111982	308	315	ouabain	Chemical	D010042
6111982	316	326	arrhythmia	Disease	D001145
6111982	345	356	GYKI-41 900	Chemical	-1
6111982	558	568	14C-41 099	Chemical	-1
6111982	CID	D010042	D001145

3123611|t|Chorea associated with oral contraception.
3123611|a|Three patients developed chorea while receiving oral contraceptives. Two were young patients whose chorea developed long after treatment had been started and disappeared soon after it had been discontinued. The third patient had acute amphetamine-induced chorea after prolonged oral contraception. Prolonged administration of female sex hormones is a possible cause of chorea in women who have not previously had chorea or rheumatic fever.
3123611	0	6	Chorea	Disease	D002819
3123611	23	41	oral contraception	Chemical	D003276
3123611	68	74	chorea	Disease	D002819
3123611	91	110	oral contraceptives	Chemical	D003276
3123611	142	148	chorea	Disease	D002819
3123611	278	289	amphetamine	Chemical	D000661
3123611	298	304	chorea	Disease	D002819
3123611	321	339	oral contraception	Chemical	D003276
3123611	412	418	chorea	Disease	D002819
3123611	456	462	chorea	Disease	D002819
3123611	466	481	rheumatic fever	Disease	D012213
3123611	CID	D003276	D002819
3123611	CID	D000661	D002819

761833|t|Reversal of ammonia coma in rats by L-dopa: a peripheral effect.
761833|a|Ammonia coma was produced in rats within 10 to 15 minutes of an intraperitonealinjection of 1.7 mmol NH4CL. This coma was prevented with 1.68 mmol L-dopa given by gastric intubation 15 minutes before the ammonium salt injection. The effect of L-dopa was correlated with a decrease in blood and brain ammonia, an increase in brain dopamine, and an increase in renal excretion of ammonia and urea. Intraventricular infusion of dopamine sufficient to raise the brain dopamine to the same extent did not prevent the ammonia coma nor affect the blood and brain ammonia concentrations. Bilateral nephrectomy eliminated the beneficial effect of L-dopa on blood and brain ammonia and the ammonia coma was not prevented. Thus, the reduction in blood and brain ammonia and the prevention of ammonia coma after L-dopa, can be accounted for by the peripheral effect of dopamine on renal function rather than its central action. These results provide a reasonable explanation for the beneficial effects observed in some encephalopathic patients receiving L-dopa.
761833	12	19	ammonia	Chemical	D000641
761833	20	24	coma	Disease	D003128
761833	36	42	L-dopa	Chemical	D007980
761833	65	72	Ammonia	Chemical	D000641
761833	73	77	coma	Disease	D003128
761833	166	171	NH4CL	Chemical	D000643
761833	178	182	coma	Disease	D003128
761833	212	218	L-dopa	Chemical	D007980
761833	269	282	ammonium salt	Chemical	D064751
761833	308	314	L-dopa	Chemical	D007980
761833	365	372	ammonia	Chemical	D000641
761833	395	403	dopamine	Chemical	D004298
761833	443	450	ammonia	Chemical	D000641
761833	455	459	urea	Chemical	D014508
761833	490	498	dopamine	Chemical	D004298
761833	529	537	dopamine	Chemical	D004298
761833	577	584	ammonia	Chemical	D000641
761833	585	589	coma	Disease	D003128
761833	621	628	ammonia	Chemical	D000641
761833	703	709	L-dopa	Chemical	D007980
761833	729	736	ammonia	Chemical	D000641
761833	745	752	ammonia	Chemical	D000641
761833	753	757	coma	Disease	D003128
761833	816	823	ammonia	Chemical	D000641
761833	846	853	ammonia	Chemical	D000641
761833	854	858	coma	Disease	D003128
761833	865	871	L-dopa	Chemical	D007980
761833	922	930	dopamine	Chemical	D004298
761833	1072	1087	encephalopathic	Disease	D001927
761833	1107	1113	L-dopa	Chemical	D007980
761833	CID	D000643	D003128

18589141|t|Heparin-induced thrombocytopenia after liver transplantation.
18589141|a|BACKGROUND: Unfractionated heparin sodium (UFH) or low-molecular weight heparin (LMWH) is used in anticoagulant protocols at several institutions to prevent thrombosis after liver transplantation. Heparin-induced thrombocytopenia (HIT) is an adverse immune-mediated reaction to heparin, resulting in platelet count decreases of more than 50%. The frequencies of HIT after liver transplantation and platelet factor 4/heparin-reactive antibody (HIT antibody) positivity in liver transplantation patients, however, are unknown. PATIENTS AND METHODS: The 32 men and 20 women underwent living donor liver transplantation. We started LMWH (25 IU/kg/h) on postoperative day (POD) 1, switching to UFH (5000 U/d) on POD 2 or 3. The dose of UFH was changed according to the activated clotting time level. HIT antibody levels were measured the day before surgery and on POD 7 and 14. Platelet count was measured daily for 3 weeks. RESULTS: The average platelet counts preoperatively, and on POD 7, 14, and 21 were 65, 88, 149, and 169 x 10(9)/L, respectively. Two patients developed hepatic artery thrombosis on POD 11 and 19, respectively, although they were HIT antibody-negative and their platelet counts were stable. In 2 other patients, the platelet count decreased suddenly from 107 x 10(9)/L on POD 4 to 65 x 10(9)/L on POD 6 and from 76 x 10(9)/L on POD 7 to 33 x 10(9)/L on POD 9, respectively. The heparin-induced platelet aggregation test was negative in these patients. The percentage of HIT antibody-positive patients was 0.5% preoperatively, 5.6% on POD 7, and 5.6% on POD 14. None of the subjects/patients developed UFH-related HIT. CONCLUSIONS: In our series, the occurrence of HIT after liver transplantation was uncommon.
18589141	0	7	Heparin	Chemical	D006493
18589141	16	32	thrombocytopenia	Disease	D013921
18589141	74	103	Unfractionated heparin sodium	Chemical	D006493
18589141	105	108	UFH	Chemical	D006493
18589141	113	141	low-molecular weight heparin	Chemical	D006495
18589141	219	229	thrombosis	Disease	D013927
18589141	259	266	Heparin	Chemical	D006493
18589141	275	291	thrombocytopenia	Disease	D013921
18589141	293	296	HIT	Disease	D013921
18589141	340	347	heparin	Chemical	D006493
18589141	424	427	HIT	Disease	D013921
18589141	478	485	heparin	Chemical	D006493
18589141	505	508	HIT	Disease	D013921
18589141	751	754	UFH	Chemical	D006493
18589141	793	796	UFH	Chemical	D006493
18589141	857	860	HIT	Disease	D013921
18589141	1149	1159	thrombosis	Disease	D013927
18589141	1211	1214	HIT	Disease	D013921
18589141	1459	1466	heparin	Chemical	D006493
18589141	1475	1495	platelet aggregation	Disease	D001791
18589141	1551	1554	HIT	Disease	D013921
18589141	1682	1685	UFH	Chemical	D006493
18589141	1694	1697	HIT	Disease	D013921
18589141	1745	1748	HIT	Disease	D013921
18589141	CID	D006493	D013921

16418614|t|PTU-associated vasculitis in a girl with Turner Syndrome and Graves' disease.
16418614|a|Palpable purpura is a concerning clinical finding in pediatric patients and can have many causes, including infectious and autoimmune processes. A rare cause, drug-induced vasculitis, may result from the production of antineutrophil cytoplasmic antibodies (ANCAs) in response to a medication. We report a girl with Turner syndrome and Graves' disease who presented with palpable purpuric lesions. The diagnosis of propylthiouracil (PTU)-associated vasculitis was made by observation of consistent clinical features, the detection of elevated ANA and ANCA in the blood, and the observed clinical resolution of symptoms following withdrawal of PTU. Subsequent treatment of persistent hyperthyroidism with radioablation did not result in an exacerbation of the vasculitis, a complication described in prior case reports.
16418614	0	3	PTU	Chemical	D011441
16418614	15	25	vasculitis	Disease	D014657
16418614	41	56	Turner Syndrome	Disease	D014424
16418614	61	76	Graves' disease	Disease	D006111
16418614	87	94	purpura	Disease	D011693
16418614	250	260	vasculitis	Disease	D014657
16418614	393	408	Turner syndrome	Disease	D014424
16418614	413	428	Graves' disease	Disease	D006111
16418614	457	473	purpuric lesions	Disease	D011693
16418614	492	508	propylthiouracil	Chemical	D011441
16418614	510	513	PTU	Chemical	D011441
16418614	526	536	vasculitis	Disease	D014657
16418614	720	723	PTU	Chemical	D011441
16418614	760	775	hyperthyroidism	Disease	D006980
16418614	836	846	vasculitis	Disease	D014657
16418614	CID	D011441	D014657

15893386|t|Succinylcholine-induced masseter muscle rigidity during bronchoscopic removal of a tracheal foreign body.
15893386|a|Masseter muscle rigidity during general anesthesia is considered an early warning sign of a possible episode of malignant hyperthermia. The decision whether to continue or discontinue the procedure depends on the urgency of the surgery and severity of masseter muscle rigidity. Here, we describe a case of severe masseter muscle rigidity (jaw of steel) after succinylcholine (Sch) administration during general anesthetic management for rigid bronchoscopic removal of a tracheal foreign body. Anesthesia was continued uneventfully with propofol infusion while all facilities were available to detect and treat malignant hyperthermia.
15893386	0	15	Succinylcholine	Chemical	D013390
15893386	24	48	masseter muscle rigidity	Disease	D014313
15893386	106	130	Masseter muscle rigidity	Disease	D014313
15893386	218	240	malignant hyperthermia	Disease	D008305
15893386	358	382	masseter muscle rigidity	Disease	D014313
15893386	419	443	masseter muscle rigidity	Disease	D014313
15893386	445	457	jaw of steel	Disease	D014313
15893386	465	480	succinylcholine	Chemical	D013390
15893386	482	485	Sch	Chemical	D013390
15893386	642	650	propofol	Chemical	D015742
15893386	716	738	malignant hyperthermia	Disease	D008305
15893386	CID	D013390	D014313

15814210|t|Minor neurological dysfunction, cognitive development, and somatic development at the age of 3 to 7 years after dexamethasone treatment in very-low birth-weight infants.
15814210|a|The objective of this study was to assess minor neurological dysfunction, cognitive development, and somatic development after dexamethasone therapy in very-low-birthweight infants. Thirty-three children after dexamethasone treatment were matched to 33 children without dexamethasone treatment. Data were assessed at the age of 3-7 years. Dexamethasone was started between the 7th and the 28th day of life over 7 days with a total dose of 2.35 mg/kg/day. Exclusion criteria were asphyxia, malformations, major surgical interventions, small for gestational age, intraventricular haemorrhage grades III and IV, periventricular leukomalacia, and severe psychomotor retardation. Each child was examined by a neuropediatrician for minor neurological dysfunctions and tested by a psychologist for cognitive development with a Kaufman Assessment Battery for Children and a Draw-a-Man Test. There were no differences in demographic data, growth, and socio-economic status between the two groups. Fine motor skills and gross motor function were significantly better in the control group (p<0.01). In the Draw-a-Man Test, the control group showed better results (p<0.001). There were no differences in development of speech, social development, and the Kaufman Assessment Battery for Children. After dexamethasone treatment, children showed a higher rate of minor neurological dysfunctions. Neurological development was affected even without neurological diagnosis. Further long-term follow-up studies will be necessary to fully evaluate the impact of dexamethasone on neurological and cognitive development.
15814210	6	30	neurological dysfunction	Disease	D009422
15814210	112	125	dexamethasone	Chemical	D003907
15814210	218	242	neurological dysfunction	Disease	D009422
15814210	297	310	dexamethasone	Chemical	D003907
15814210	380	393	dexamethasone	Chemical	D003907
15814210	440	453	dexamethasone	Chemical	D003907
15814210	509	522	Dexamethasone	Chemical	D003907
15814210	649	657	asphyxia	Disease	D001237
15814210	659	672	malformations	Disease	D000014
15814210	748	759	haemorrhage	Disease	D006470
15814210	779	807	periventricular leukomalacia	Disease	D007969
15814210	820	843	psychomotor retardation	Disease	D011596
15814210	902	927	neurological dysfunctions	Disease	D009422
15814210	1460	1473	dexamethasone	Chemical	D003907
15814210	1524	1549	neurological dysfunctions	Disease	D009422
15814210	1712	1725	dexamethasone	Chemical	D003907
15814210	CID	D003907	D009422

11912119|t|Force overflow and levodopa-induced dyskinesias in Parkinson's disease.
11912119|a|We assessed force coordination of the hand in Parkinson's disease and its relationship to motor complications of levodopa therapy, particularly to levodopa-induced dyskinesias (LID). We studied two groups of Parkinson's disease patients with (Parkinson's disease + LID, n = 23) and without levodopa-induced dyskinesias (Parkinson's disease - LID, n = 10), and age-matched healthy controls. The motor score of the Unified Parkinson's Disease Rating Scale, a dyskinesia score and force in a grip-lift paradigm were assessed ON and OFF levodopa. A pathological increase of forces was seen in ON-state in Parkinson's disease + LID only. In Parkinson's disease + LID, the force involved in pressing down the object before lifting was significantly increased by levodopa (by 61%, P < 0.05). An overshooting of peak grip force by 51% (P < 0.05) and of static grip force by 45% (P < 0.01) was observed in the ON- compared with the OFF-drug condition. In contrast, no excessive force was found in Parkinson's disease - LID. Peak grip force in ON-state was 140% (P < 0.05) higher in Parkinson's disease + LID than in Parkinson's disease - LID, while static grip force was increased by 138% (P < 0.01) between groups. Severity of peak-dose dyskinesias was strongly correlated with grip force in ON-state (r = 0.79 with peak force, P < 0.01). No correlation was observed between forces and the motor score as well as with the daily dose of dopaminergic medication. Force excess was only observed in patients with LID and motor fluctuations. A close relationship was seen between the overshooting of forces and dyskinesias in the ON-drug condition. We postulate that both LID and grip force excess share common pathophysiological mechanisms related to motor fluctuations.
11912119	19	27	levodopa	Chemical	D007980
11912119	36	47	dyskinesias	Disease	D004409
11912119	51	70	Parkinson's disease	Disease	D010300
11912119	118	137	Parkinson's disease	Disease	D010300
11912119	185	193	levodopa	Chemical	D007980
11912119	219	227	levodopa	Chemical	D007980
11912119	236	247	dyskinesias	Disease	D004409
11912119	249	252	LID	Disease	D004409
11912119	280	299	Parkinson's disease	Disease	D010300
11912119	315	334	Parkinson's disease	Disease	D010300
11912119	337	340	LID	Disease	D004409
11912119	362	370	levodopa	Chemical	D007980
11912119	379	390	dyskinesias	Disease	D004409
11912119	392	411	Parkinson's disease	Disease	D010300
11912119	414	417	LID	Disease	D004409
11912119	493	512	Parkinson's Disease	Disease	D010300
11912119	529	539	dyskinesia	Disease	D004409
11912119	605	613	levodopa	Chemical	D007980
11912119	673	692	Parkinson's disease	Disease	D010300
11912119	695	698	LID	Disease	D004409
11912119	708	727	Parkinson's disease	Disease	D010300
11912119	730	733	LID	Disease	D004409
11912119	828	836	levodopa	Chemical	D007980
11912119	1060	1079	Parkinson's disease	Disease	D010300
11912119	1082	1085	LID	Disease	D004409
11912119	1145	1164	Parkinson's disease	Disease	D010300
11912119	1167	1170	LID	Disease	D004409
11912119	1179	1198	Parkinson's disease	Disease	D010300
11912119	1201	1204	LID	Disease	D004409
11912119	1301	1312	dyskinesias	Disease	D004409
11912119	1573	1576	LID	Disease	D004409
11912119	1670	1681	dyskinesias	Disease	D004409
11912119	1731	1734	LID	Disease	D004409
11912119	CID	D007980	D004409

9105126|t|Postinfarction ventricular septal defect associated with long-term steroid therapy.
9105126|a|Two cases of postinfarction ventricular septal rupture in patients on long-term steroid therapy are presented and the favourable outcome in both cases described. A possible association between steroid therapy and subsequent postinfarction septal rupture is discussed.
9105126	15	40	ventricular septal defect	Disease	D018658
9105126	67	74	steroid	Chemical	D013256
9105126	112	138	ventricular septal rupture	Disease	D018658
9105126	164	171	steroid	Chemical	D013256
9105126	277	284	steroid	Chemical	D013256
9105126	323	337	septal rupture	Disease	D018658
9105126	CID	D013256	D018658

8599504|t|Angioedema associated with droperidol administration.
8599504|a|Angioedema, also known as angioneurotic edema or Quincke's disease, is a well-demarcated, localized edema involving the subcutaneous tissues that may cause upper-airway obstruction. We report the case of a previously healthy 19-year-old man with no known drug allergies in whom angioedema with significant tongue swelling and protrusion developed within 10 minutes of the administration of a single IV dose of droperidol.
8599504	0	10	Angioedema	Disease	D000799
8599504	27	37	droperidol	Chemical	D004329
8599504	54	64	Angioedema	Disease	D000799
8599504	80	99	angioneurotic edema	Disease	D000799
8599504	103	120	Quincke's disease	Disease	D000799
8599504	154	159	edema	Disease	D004487
8599504	210	234	upper-airway obstruction	Disease	D000402
8599504	309	323	drug allergies	Disease	D004342
8599504	332	342	angioedema	Disease	D000799
8599504	360	375	tongue swelling	Disease	D014060|D004487	tongue swelling|swelling
8599504	464	474	droperidol	Chemical	D004329
8599504	CID	D004329	D000799

8546130|t|Clarithromycin-associated visual hallucinations in a patient with chronic renal failure on continuous ambulatory peritoneal dialysis.
8546130|a|Visual hallucinations are a rare event in chronic renal failure and not related to uremia per se. Unreported in the literature is visual hallucinations occurring in association with the new macrolide antibiotic, clarithromycin. We describe such a case in a patient with end-stage renal disease (ESRD) maintained on continuous ambulatory peritoneal dialysis (CAPD). The combination of a relatively high dose of clarithromycin in face of chronic renal failure in a functionally anephric patient, with underlying aluminum intoxication, may have facilitated the appearance of this neurotoxic side effect. It is important to understand the pharmacokinetics of medications in face of chronic renal failure, the possibility of drug interactions, and how these factors should help guide medication therapy in the ESRD patient.
8546130	0	14	Clarithromycin	Chemical	D017291
8546130	26	47	visual hallucinations	Disease	D006212
8546130	66	87	chronic renal failure	Disease	D007676
8546130	134	155	Visual hallucinations	Disease	D006212
8546130	176	197	chronic renal failure	Disease	D007676
8546130	217	223	uremia	Disease	D014511
8546130	264	285	visual hallucinations	Disease	D006212
8546130	324	333	macrolide	Chemical	D018942
8546130	346	360	clarithromycin	Chemical	D017291
8546130	404	427	end-stage renal disease	Disease	D007676
8546130	429	433	ESRD	Disease	D007676
8546130	544	558	clarithromycin	Chemical	D017291
8546130	570	591	chronic renal failure	Disease	D007676
8546130	644	652	aluminum	Chemical	D000535
8546130	711	721	neurotoxic	Disease	D020258
8546130	812	833	chronic renal failure	Disease	D007676
8546130	939	943	ESRD	Disease	D007676
8546130	CID	D017291	D006212

7724492|t|Acute renal toxicity of doxorubicin (adriamycin)-loaded cyanoacrylate nanoparticles.
7724492|a|Acute doxorubicin-loaded nanoparticle (DXNP) renal toxicity was explored in both normal rats and rats with experimental glomerulonephritis. In normal rats, 2/6 rats given free doxorubicin (DX) (5 mg/kg) died within one week, whereas all control animals and all rats having received free NP or DXNP survived. A 3 times higher proteinuria appeared in animals treated with DXNP than in those treated with DX. Free NP did not provoke any proteinuria. Two hr post-injection, DXNP was 2.7 times more concentrated in kidneys than free DX (p < 0.025). In rats with immune experimental glomerulonephritis, 5/6 rats given DX died within 7 days, in contrast to animals treated by DXNP, NP, or untreated, which all survived. Proteinuria appeared in all series, but was 2-5 times more intense (p > 0.001) and prolonged after doxorubicin treatment (400-700 mg/day), without significant difference between DXNP and DX. Rats treated by unloaded NP behaved as controls. These results demonstrate that, in these experimental conditions, DXNP killed less animals than free DX, despite of an enhanced renal toxicity of the former. Both effects (better survival and nephrosis) are most probably related to an enhanced capture of DXNP by cells of the mononuclear phagocyte system, including mesangial cells.
7724492	6	20	renal toxicity	Disease	D007674
7724492	24	35	doxorubicin	Chemical	D004317
7724492	37	47	adriamycin	Chemical	D004317
7724492	56	69	cyanoacrylate	Chemical	D003487
7724492	91	102	doxorubicin	Chemical	D004317
7724492	130	144	renal toxicity	Disease	D007674
7724492	205	223	glomerulonephritis	Disease	D005921
7724492	261	272	doxorubicin	Chemical	D004317
7724492	274	276	DX	Chemical	D004317
7724492	410	421	proteinuria	Disease	D011507
7724492	487	489	DX	Chemical	D004317
7724492	519	530	proteinuria	Disease	D011507
7724492	613	615	DX	Chemical	D004317
7724492	662	680	glomerulonephritis	Disease	D005921
7724492	697	699	DX	Chemical	D004317
7724492	798	809	Proteinuria	Disease	D011507
7724492	897	908	doxorubicin	Chemical	D004317
7724492	985	987	DX	Chemical	D004317
7724492	1139	1141	DX	Chemical	D004317
7724492	1166	1180	renal toxicity	Disease	D007674
7724492	1230	1239	nephrosis	Disease	D009401
7724492	CID	D004317	D011507

7619765|t|Etoposide-related myocardial infarction.
7619765|a|The occurrence of a myocardial infarction is reported after chemotherapy containing etoposide, in a man with no risk factors for coronary heart disease. Possible causal mechanisms are discussed.
7619765	0	9	Etoposide	Chemical	D005047
7619765	18	39	myocardial infarction	Disease	D009203
7619765	61	82	myocardial infarction	Disease	D009203
7619765	125	134	etoposide	Chemical	D005047
7619765	170	192	coronary heart disease	Disease	D003327
7619765	CID	D005047	D009203

7416947|t|Subjective assessment of sexual dysfunction of patients on long-term administration of digoxin.
7416947|a|Various data suggest that male patients who have received digoxin on a longterm basis have increased levels of serum estrogen and decreased levels of plasma testosterone and luteinizing hormone (LH). This study was undertaken to investigate the links between the long-term administration of digoxin therapy and sexual behavior, and the effect of digoxin on plasma levels of estradiol, testosterone, and LH. The patients of the study and control group (without digoxin) were of similar cardiac functional capacity and age (25-40 years) and were randomly selected from the rheumatic heart disease patients. A subjective assessment of sexual behavior in the study and control groups was carried out, using parameters such as sexual desire, sexual excitement, and frequency of sexual relations. Personal interviews and a questionnaire were also used for the evaluation of sexual behavior. The findings support the reports concerning digoxin effect on plasma estradiol, testosterone, and LH. The differences in the means were significant. Tests used to evaluate the changes in sexual behavior showed a significant decrease in sexual desire, sexual excitement phase (erection), and frequency of sexual relations in the study group.
7416947	25	43	sexual dysfunction	Disease	D020018
7416947	87	94	digoxin	Chemical	D004077
7416947	154	161	digoxin	Chemical	D004077
7416947	213	221	estrogen	Chemical	D004967
7416947	253	265	testosterone	Chemical	D013739
7416947	387	394	digoxin	Chemical	D004077
7416947	442	449	digoxin	Chemical	D004077
7416947	470	479	estradiol	Chemical	D004958
7416947	481	493	testosterone	Chemical	D013739
7416947	556	563	digoxin	Chemical	D004077
7416947	667	690	rheumatic heart disease	Disease	D012214
7416947	1025	1032	digoxin	Chemical	D004077
7416947	1050	1059	estradiol	Chemical	D004958
7416947	1061	1073	testosterone	Chemical	D013739
7416947	1205	1230	decrease in sexual desire	Disease	D020018
7416947	CID	D004077	D020018

7263204|t|Fatal aplastic anemia due to indomethacin--lymphocyte transformation tests in vitro.
7263204|a|Although indomethacin has been implicated as a possible cause of aplastic anemia on the basis of a few clinical observations, its role has not been definitely established. A case of fatal aplastic anemia is described in which no drugs other than allopurinol and indomethacin were given. Indomethacin was first given four weeks prior to the onset of symptoms. A positive lymphocyte transformation test with indomethacin in vitro further substantiates the potential role of this drug in causing aplastic anemia in a susceptible patient. Fortunately, this seems to be a very rare complication.
7263204	6	21	aplastic anemia	Disease	D000741
7263204	29	41	indomethacin	Chemical	D007213
7263204	94	106	indomethacin	Chemical	D007213
7263204	150	165	aplastic anemia	Disease	D000741
7263204	273	288	aplastic anemia	Disease	D000741
7263204	331	342	allopurinol	Chemical	D000493
7263204	347	359	indomethacin	Chemical	D007213
7263204	372	384	Indomethacin	Chemical	D007213
7263204	491	503	indomethacin	Chemical	D007213
7263204	578	593	aplastic anemia	Disease	D000741
7263204	CID	D007213	D000741

7066357|t|Plasma and urinary lipids and lipoproteins during the development of nephrotic syndrome induced in the rat by puromycin aminonucleoside.
7066357|a|This study was undertaken to ascertain whether the alterations of plasma lipoproteins found in nephrotic syndrome induced by puromycin aminonucleoside were due to nephrotic syndrome per se, or, at least in part, to the aminonucleoside. The purpose of the present study was to investigate the changes in plasma and urinary lipoproteins during the administration of puromycin aminonucleoside (20 mg/kg for 7 days) and the subsequent development of nephrotic syndrome. Since massive albuminuria occurred after 6 days of treatment, the time-course study was divided into two stages: pre-nephrotic stage (day 1-5) and nephrotic stage (day 6-11). In pre-nephrotic stage the plasma level of fatty acids, triacylglycerol and VLDL decreased while that of phospholipid, cholesteryl esters and HDL remained constant. Plasma apolipoprotein A-I tended to increase (40% increase at day 5). At the beginning of nephrotic stage (day 6) the concentration of plasma albumin dropped to a very low level, while that of apolipoprotein A-I increased abruptly (4-fold increase) and continued to rise, although less steeply, in the following days. The plasma concentration of HDL followed the same pattern. Plasma VLDL and LDL increased at a later stage (day 9). Plasma apolipoprotein A-I was found not only in HDL (1.063-1.210 g/ml) but also in the LDL density class (1.025-1.050 g/ml). In the pre-nephrotic stage lipoproteinuria was negligible, while in the early nephrotic stage the urinary loss of plasma lipoproteins consisted mainly of HDL. These observations indicate that puromycin aminonucleoside alters plasma lipoproteins by lowering VLDL and increasing HDL. It is likely that the early and striking increase of plasma HDL found in nephrotic rats is related to a direct effect of the drug on HDL metabolism.
7066357	69	87	nephrotic syndrome	Disease	D009404
7066357	110	135	puromycin aminonucleoside	Chemical	D011692
7066357	232	250	nephrotic syndrome	Disease	D009404
7066357	262	287	puromycin aminonucleoside	Chemical	D011692
7066357	300	318	nephrotic syndrome	Disease	D009404
7066357	356	371	aminonucleoside	Chemical	D011692
7066357	501	526	puromycin aminonucleoside	Chemical	D011692
7066357	583	601	nephrotic syndrome	Disease	D009404
7066357	617	628	albuminuria	Disease	D000419
7066357	720	729	nephrotic	Disease	D009404
7066357	750	759	nephrotic	Disease	D009404
7066357	785	794	nephrotic	Disease	D009404
7066357	821	832	fatty acids	Chemical	D005227
7066357	834	849	triacylglycerol	Chemical	D014280
7066357	897	915	cholesteryl esters	Chemical	D002788
7066357	1033	1042	nephrotic	Disease	D009404
7066357	1512	1521	nephrotic	Disease	D009404
7066357	1579	1588	nephrotic	Disease	D009404
7066357	1693	1718	puromycin aminonucleoside	Chemical	D011692
7066357	1856	1865	nephrotic	Disease	D009404
7066357	CID	D011692	D009404

7007443|t|Circulating lysosomal enzymes and acute hepatic necrosis.
7007443|a|The activities of the lysosomal enzymes acid and neutral protease, N-acetylglucosaminidase, and acid phosphatase were measured in the serum of patients with fulminant hepatic failure. Acid protease (cathepsin D) activity was increased about tenfold in patients who died and nearly fourfold in those who survived fulminant hepatic failure after paracetamol overdose, whereas activities were increased equally in patients with fulminant hepatic failure due to viral hepatitis whether or not they survived. A correlation was found between serum acid protease activity and prothrombin time, and the increase in cathepsin D activity was sustained over several days compared with aspartate aminotransferase, which showed a sharp early peak and then a fall. Circulating lysosomal proteases can damage other organs, and measurement of their activity may therefore be of added value in assessing prognosis in this condition.
7007443	34	56	acute hepatic necrosis	Disease	D017114
7007443	215	240	fulminant hepatic failure	Disease	D017114
7007443	370	395	fulminant hepatic failure	Disease	D017114
7007443	402	413	paracetamol	Chemical	D000082
7007443	414	422	overdose	Disease	D062787
7007443	483	508	fulminant hepatic failure	Disease	D017114
7007443	516	531	viral hepatitis	Disease	D006525
7007443	732	741	aspartate	Chemical	D001224
7007443	CID	D000082	D017114

3762968|t|Transketolase abnormality in tolazamide-induced Wernicke's encephalopathy.
3762968|a|We studied a thiamine-dependent enzyme, transketolase, from fibroblasts of a diabetic patient who developed Wernicke's encephalopathy when treated with tolazamide, in order to delineate if this patient also had transketolase abnormality [high Km for thiamine pyrophosphate (TPP)], as previously reported in postalcoholic Wernicke-Korsakoff syndrome. In addition to this patient, we also studied this enzyme from three diabetic kindreds without any history of Wernicke's encephalopathy and from four normal controls. We found that the above-mentioned patient and one of the diabetic kindreds with no history of Wernicke's encephalopathy had abnormal transketolase as determined by its Km for TPP. These data suggest a similarity between postalcoholic Wernicke-Korsakoff syndrome and the patient with tolazamide-induced Wernicke's encephalopathy from the standpoint of transketolase abnormality.
3762968	29	39	tolazamide	Chemical	D014042
3762968	48	73	Wernicke's encephalopathy	Disease	D014899
3762968	88	96	thiamine	Chemical	D013831
3762968	152	160	diabetic	Disease	D003920
3762968	183	208	Wernicke's encephalopathy	Disease	D014899
3762968	227	237	tolazamide	Chemical	D014042
3762968	325	347	thiamine pyrophosphate	Chemical	D013835
3762968	349	352	TPP	Chemical	D013835
3762968	396	423	Wernicke-Korsakoff syndrome	Disease	D020915
3762968	493	501	diabetic	Disease	D003920
3762968	534	559	Wernicke's encephalopathy	Disease	D014899
3762968	648	656	diabetic	Disease	D003920
3762968	685	710	Wernicke's encephalopathy	Disease	D014899
3762968	766	769	TPP	Chemical	D013835
3762968	825	852	Wernicke-Korsakoff syndrome	Disease	D020915
3762968	874	884	tolazamide	Chemical	D014042
3762968	893	918	Wernicke's encephalopathy	Disease	D014899
3762968	CID	D014042	D014899

3413271|t|Mechanisms of myocardial ischemia induced by epinephrine: comparison with exercise-induced ischemia.
3413271|a|The role of epinephrine in eliciting myocardial ischemia was examined in patients with coronary artery disease. Objective signs of ischemia and factors increasing myocardial oxygen consumption were compared during epinephrine infusion and supine bicycle exercise. Both epinephrine and exercise produced myocardial ischemia as evidenced by ST segment depression and angina. However, the mechanisms of myocardial ischemia induced by epinephrine were significantly different from those of exercise. Exercise-induced myocardial ischemia was marked predominantly by increased heart rate and rate-pressure product with a minor contribution of end-diastolic volume, while epinephrine-induced ischemia was characterized by a marked increase in contractility and a less pronounced increase in heart rate and rate-pressure product. These findings indicate that ischemia produced by epinephrine, as may occur during states of emotional distress, has a mechanism distinct from that due to physical exertion.
3413271	14	33	myocardial ischemia	Disease	D017202
3413271	45	56	epinephrine	Chemical	D004837
3413271	91	99	ischemia	Disease	D007511
3413271	113	124	epinephrine	Chemical	D004837
3413271	138	157	myocardial ischemia	Disease	D017202
3413271	188	211	coronary artery disease	Disease	D003324
3413271	232	240	ischemia	Disease	D007511
3413271	275	281	oxygen	Chemical	D010100
3413271	315	326	epinephrine	Chemical	D004837
3413271	370	381	epinephrine	Chemical	D004837
3413271	404	423	myocardial ischemia	Disease	D017202
3413271	451	461	depression	Disease	D003866
3413271	466	472	angina	Disease	D000787
3413271	501	520	myocardial ischemia	Disease	D017202
3413271	532	543	epinephrine	Chemical	D004837
3413271	614	633	myocardial ischemia	Disease	D017202
3413271	766	777	epinephrine	Chemical	D004837
3413271	786	794	ischemia	Disease	D007511
3413271	952	960	ischemia	Disease	D007511
3413271	973	984	epinephrine	Chemical	D004837
3413271	CID	D004837	D017202

3088349|t|Transient contralateral rotation following unilateral substantia nigra lesion reflects susceptibility of the nigrostriatal system to exhaustion by amphetamine.
3088349|a|Following unilateral 6-OHDA induced SN lesion, a transient period of contralateral rotation has been reported to precede the predominant ipsilateral circling. In order to clarify the nature of this initial contralateral rotation we examined the effect of the duration of recovery period after the lesion, on amphetamine-induced rotational behavior. Three days post lesion, most rats circled predominantly contralaterally to the lesion. Such contralateral rotation may result from either degeneration-induced breakdown of the DA pool, or lesion-induced increase of DA turnover in the spared neurons. A substantial degree of contralateral preference was still evident when amphetamine was administered for the first time 24 days after lesioning, indicating involvement of spared cells in the contralateral rotation. However, regardless of the duration of recovery (and irrespective of either lesion volume, amphetamine dose, or post-lesion motor exercise), amphetamine-induced rotation tended to become gradually more ipsilateral as the observation session progressed, and all rats circled ipsilaterally to the lesion in response to further amphetamine injections. These findings suggest that amphetamine has an irreversible effect on the post-lesion DA pool contributing to contralateral rotation.
3088349	10	32	contralateral rotation	Disease	D009069
3088349	54	77	substantia nigra lesion	Disease	-1
3088349	147	158	amphetamine	Chemical	D000661
3088349	181	187	6-OHDA	Chemical	D016627
3088349	196	205	SN lesion	Disease	-1
3088349	229	251	contralateral rotation	Disease	D009069
3088349	297	317	ipsilateral circling	Disease	D009069
3088349	366	388	contralateral rotation	Disease	D009069
3088349	468	479	amphetamine	Chemical	D000661
3088349	488	507	rotational behavior	Disease	D009069
3088349	601	623	contralateral rotation	Disease	D009069
3088349	831	842	amphetamine	Chemical	D000661
3088349	950	972	contralateral rotation	Disease	D009069
3088349	1065	1076	amphetamine	Chemical	D000661
3088349	1115	1126	amphetamine	Chemical	D000661
3088349	1135	1143	rotation	Disease	D009069
3088349	1299	1310	amphetamine	Chemical	D000661
3088349	1351	1362	amphetamine	Chemical	D000661
3088349	1433	1455	contralateral rotation	Disease	D009069
3088349	CID	D000661	D009069

3001299|t|Thyroid function and urine-concentrating ability during lithium treatment.
3001299|a|It has been suggested that adenylate cyclase inhibition may be important in the development of both nephrogenic diabetes insipidus and hypothyroidism during lithium treatment. We measured serum thyroxine and urine-concentrating ability (Umax) in response to desmopressin (DDAVP) in 85 patients receiving lithium. Hypothyroidism developed in eight patients while they were taking lithium. Impaired Umax was found in both euthyroid and hypothyroid patients while some hypothyroid patients concentrated their urine well. It is concluded that the dominant mechanisms by which lithium exerts these two effects are different.
3001299	56	63	lithium	Chemical	D008094
3001299	175	205	nephrogenic diabetes insipidus	Disease	D018500
3001299	210	224	hypothyroidism	Disease	D007037
3001299	232	239	lithium	Chemical	D008094
3001299	269	278	thyroxine	Chemical	D013974
3001299	379	386	lithium	Chemical	D008094
3001299	388	402	Hypothyroidism	Disease	D007037
3001299	454	461	lithium	Chemical	D008094
3001299	509	520	hypothyroid	Disease	D007037
3001299	541	552	hypothyroid	Disease	D007037
3001299	647	654	lithium	Chemical	D008094
3001299	CID	D008094	D007037

2004015|t|Sensitivity of erythroid progenitor colonies to erythropoietin in azidothymidine treated immunodeficient mice.
2004015|a|The anaemia induced by 3'-azido-3'dideoxythymidine (AZT) is poorly understood. We have used a murine model of AIDS, infection of female C57BL/6 mice with LP-BM5 murine leukaemia (MuLV) virus, to determine if AZT-induced anaemia is due, in part, to decreased responsiveness of erythropoietic precursors (BFU-e) to erythropoietin (EPO). Mice in the early stage of LP-BM5 MuLV disease were given AZT in their drinking water at 1.0 and 2.5 mg/ml. AZT produced anaemia in both groups, in a dose-dependent fashion. Despite the anaemia, the number of splenic and bone marrow BFU-e in AZT treated mice increased up to five-fold over levels observed in infected untreated animals after 15 d of treatment. Colony formation by splenic and bone marrow BFUe was stimulated at lower concentrations of EPO in mice receiving AZT for 15 d than for infected, untreated mice. By day 30, sensitivity of both splenic and bone marrow BFU-e of treated animals returned to that observed from cells of infected untreated animals. The mean plasma levels of EPO observed in AZT treated mice were appropriate for the degree of anaemia observed when compared with phenylhydrazine (PHZ) treated mice. The numbers of BFU-e and the percentage of bone marrow erythroblasts observed were comparable in AZT and PHZ treated mice with similar degrees of anaemia. However, reticulocytosis was inappropriate for the degree of anaemia observed in AZT treated infected mice. AZT-induced peripheral anaemia in the face of increased numbers of BFU-e and increased levels of plasma EPO suggest a lesion in terminal differentiation.
2004015	66	80	azidothymidine	Chemical	D015215
2004015	89	104	immunodeficient	Disease	C565469
2004015	115	122	anaemia	Disease	D000740
2004015	134	161	3'-azido-3'dideoxythymidine	Chemical	D015215
2004015	163	166	AZT	Chemical	D015215
2004015	221	225	AIDS	Disease	D000163
2004015	227	236	infection	Disease	D007239
2004015	279	288	leukaemia	Disease	D007938
2004015	319	322	AZT	Chemical	D015215
2004015	331	338	anaemia	Disease	D000740
2004015	504	507	AZT	Chemical	D015215
2004015	554	557	AZT	Chemical	D015215
2004015	567	574	anaemia	Disease	D000740
2004015	632	639	anaemia	Disease	D000740
2004015	688	691	AZT	Chemical	D015215
2004015	920	923	AZT	Chemical	D015215
2004015	1158	1161	AZT	Chemical	D015215
2004015	1210	1217	anaemia	Disease	D000740
2004015	1246	1261	phenylhydrazine	Chemical	C030299
2004015	1263	1266	PHZ	Chemical	C030299
2004015	1379	1382	AZT	Chemical	D015215
2004015	1387	1390	PHZ	Chemical	C030299
2004015	1428	1435	anaemia	Disease	D000740
2004015	1446	1461	reticulocytosis	Disease	D045262
2004015	1498	1505	anaemia	Disease	D000740
2004015	1518	1521	AZT	Chemical	D015215
2004015	1545	1548	AZT	Chemical	D015215
2004015	1568	1575	anaemia	Disease	D000740
2004015	CID	D015215	D000740

1732442|t|Detection of abnormal cardiac adrenergic neuron activity in adriamycin-induced cardiomyopathy with iodine-125-metaiodobenzylguanidine.
1732442|a|Radiolabeled metaiodobenzylguanidine (MIBG), an analog of norepinephrine (NE), serves as an index of adrenergic neuron integrity and function. Using a rat model of adriamycin-induced cardiomyopathy, we tested the hypothesis that abnormal cardiac adrenergic neuron activity may appear and be exacerbated dose-dependently in adriamycin cardiomyopathy. The degree of vacuolar degeneration of myocardial cells was analyzed in relation to the duration of adriamycin treatment (2 mg/kg, once a week). There were no abnormalities or only isolated degeneration in the 1- or 2-wk treatment groups, isolated or scattered degeneration in half of the 3-wk group, frequent scattered degeneration in the 4-wk group, scattered or focal degeneration in the 5-wk group, and extensive degeneration in the 8-wk group. Myocardial accumulation of [125I]MIBG 4 hr after intravenous injection did not differ between the controls and the groups treated 3 wk or less. However, the 4-wk group had a slightly lower accumulation in the right ventricular wall (82% of the control) and significantly lower accumulation in the left ventricular wall (about 66% of the control: p less than 0.05). In the 5-wk group, MIBG accumulation in the right and left ventricular wall was 35% and 27% of that in controls, respectively (p less than 0.001). In the 8-wk group, MIBG accumulation in the right and left ventricular wall was 18% and 14% of that in controls, respectively (p less than 0.001). Thus, MIBG accumulation in the myocardium decreased in an adriamycin dose-dependent manner. The appearance of impaired cardiac adrenergic neuron activity in the presence of slight myocardial impairment (scattered or focal vacuolar degeneration) indicates that MIBG scintigraphy may be a useful method for detection of adriamycin-induced cardiomyopathy.
1732442	60	70	adriamycin	Chemical	D004317
1732442	79	93	cardiomyopathy	Disease	D009202
1732442	99	133	iodine-125-metaiodobenzylguanidine	Chemical	D019797
1732442	135	171	Radiolabeled metaiodobenzylguanidine	Chemical	D019797
1732442	173	177	MIBG	Chemical	D019797
1732442	193	207	norepinephrine	Chemical	D009638
1732442	209	211	NE	Chemical	D009638
1732442	299	309	adriamycin	Chemical	D004317
1732442	318	332	cardiomyopathy	Disease	D009202
1732442	458	468	adriamycin	Chemical	D004317
1732442	469	483	cardiomyopathy	Disease	D009202
1732442	499	540	vacuolar degeneration of myocardial cells	Disease	C536522
1732442	585	595	adriamycin	Chemical	D004317
1732442	967	971	MIBG	Chemical	D019797
1732442	1318	1322	MIBG	Chemical	D019797
1732442	1465	1469	MIBG	Chemical	D019797
1732442	1599	1603	MIBG	Chemical	D019797
1732442	1651	1661	adriamycin	Chemical	D004317
1732442	1773	1794	myocardial impairment	Disease	D009202
1732442	1815	1836	vacuolar degeneration	Disease	C536522
1732442	1853	1857	MIBG	Chemical	D019797
1732442	1911	1921	adriamycin	Chemical	D004317
1732442	1930	1944	cardiomyopathy	Disease	D009202
1732442	CID	D004317	D009202

1423339|t|Amnestic syndrome associated with propranolol toxicity: a case report.
1423339|a|An elderly woman developed an Alzheimer-like subacute dementia as a result of propranolol toxicity. Analysis of the manifestations showed that severe impairment of memory accounted for virtually all of the abnormalities. There is evidence that cerebral reactions to drug toxicity can exhibit patterns that suggest highly selective involvement of functional subdivisions of the brain.
1423339	0	17	Amnestic syndrome	Disease	D000647
1423339	34	45	propranolol	Chemical	D011433
1423339	46	54	toxicity	Disease	D064420
1423339	101	110	Alzheimer	Disease	D000544
1423339	125	133	dementia	Disease	D003704
1423339	149	160	propranolol	Chemical	D011433
1423339	161	169	toxicity	Disease	D064420
1423339	342	350	toxicity	Disease	D064420
1423339	CID	D011433	D000647

921394|t|Biphasic response of the SA node of the dog heart in vivo to selective administration of ketamine.
921394|a|Effect of ketamine on the SA node of the dog heart was studied in vivo using a selective perfusion technique of the SA node artery. Injections of ketamine in doses from 100 microgram to 3 mg into the artery produced a depression of the SA nodal activity by a direct action. This depression was followed by the sudden appearance of a stimulatory phase. Bilateral vagotomy and sympathectomy or prior administration of a ganglion blocker failed to inhibit the occurrence of the ketamine-induced tachycardia, while it was completely abolished in the reserpinized dogs or by a prior injection of a beta-blocking agent into the SA node artery. This may indicate that an activation of the peripheral adrenergic mechanism plays an important role in the induction of the excitatory effect of ketamine injected in the SA node artery.
921394	89	97	ketamine	Chemical	D007649
921394	109	117	ketamine	Chemical	D007649
921394	245	253	ketamine	Chemical	D007649
921394	317	327	depression	Disease	D003866
921394	378	388	depression	Disease	D003866
921394	574	582	ketamine	Chemical	D007649
921394	591	602	tachycardia	Disease	D013610
921394	882	890	ketamine	Chemical	D007649
921394	CID	D007649	D013610

871943|t|The use of serum cholinesterase in succinylcholine apnoea.
871943|a|Fifteen patients demonstrating unexpected prolonged apnoea lasting several hours after succinylcholine have been treated by a new preparation of human serum cholinesterase. Adequate spontaneous respiration was re-established in an average period of ten minutes after the injection. In 12 patients biochemical genetic examinations confirmed the presence of an atypical serum cholinesterase. In three patients none of the usual variants were found. It is therefore supposed that other unknown variants of serum cholinesterase exist which cannot hydrolyze succinylcholine. The use of serum cholinesterase in succinylcholine apnoea provided considerable relief to both patient and anaesthetist.
871943	35	50	succinylcholine	Chemical	D013390
871943	51	57	apnoea	Disease	D001049
871943	111	117	apnoea	Disease	D001049
871943	146	161	succinylcholine	Chemical	D013390
871943	612	627	succinylcholine	Chemical	D013390
871943	664	679	succinylcholine	Chemical	D013390
871943	680	686	apnoea	Disease	D001049
871943	CID	D013390	D001049

1355091|t|Orthostatic hypotension occurs following alpha 2-adrenoceptor blockade in chronic prazosin-pretreated conscious spontaneously hypertensive rats.
1355091|a|1. Studies were performed to evaluate whether chronic prazosin treatment alters the alpha 2-adrenoceptor function for orthostatic control of arterial blood pressure in conscious spontaneously hypertensive rats (SHR). 2. Conscious SHR (male 300-350 g) were subjected to 90 degrees head-up tilts for 60 s following acute administration of prazosin (0.1 mg kg-1 i.p.) or rauwolscine (3 mg kg-1 i.v.). Orthostatic hypotension was determined by the average decrease (%) in mean arterial pressure (MAP femoral) over the 60-s tilt period. The basal MAP of conscious SHR was reduced to a similar extent by prazosin (-23%(-)-26% MAP) and rauwolscine (-16%(-)-33% MAP). However, the head-up tilt induced orthostatic hypotension in the SHR treated with prazosin (-16% MAP, n = 6), but not in the SHR treated with rauwolscine (less than +2% MAP, n = 6). 3. Conscious SHR were treated for 4 days with prazosin at 2 mg kg-1 day-1 i.p. for chronic alpha 1-adrenoceptor blockade. MAP in conscious SHR after chronic prazosin treatment was 14% lower than in the untreated SHR (n = 8). Head-up tilts in these rats did not produce orthostatic hypotension when performed either prior to or after acute dosing of prazosin (0.1 mg kg-1 i.p.). Conversely, administration of rauwolscine (3 mg kg-1 i.v.) in chronic prazosin treated SHR decreased the basal MAP by 12-31% (n = 4), and subsequent tilts induced further drops of MAP by 19-23% in these rats. 4. The pressor responses and bradycardia to the alpha 1-agonist cirazoline (0.6 and 2 micrograms kg-1 i.v.), the alpha 2-agonist Abbott-53693 (1 and 3 micrograms kg-1 i.v.), and noradrenaline (0.1 and 1.0 micrograms kg-1 i.v.) were determined in conscious SHR with and without chronic prazosin pretreatment. Both the pressor and bradycardia effects of cirazoline were abolished in chronic prazosin treated SHR (n = 4) as compared to the untreated SHR (n = 4). On the other hand, the pressor effects of Abbott-53693 were similar in both groups of SHR, but the accompanying bradycardia was greater in SHR with chronic prazosin treatment than without such treatment. Furthermore, the bradycardia that accompanied the noradrenaline-induced pressor effect in SHR was similar with and without chronic prazosin treatment despite a 47-71% reduction of the pressor effect in chronic alpha 1-receptor blocked SHR.(ABSTRACT TRUNCATED AT 400 WORDS)
1355091	0	23	Orthostatic hypotension	Disease	D007024
1355091	82	90	prazosin	Chemical	D011224
1355091	126	138	hypertensive	Disease	D006973
1355091	199	207	prazosin	Chemical	D011224
1355091	337	349	hypertensive	Disease	D006973
1355091	482	490	prazosin	Chemical	D011224
1355091	513	524	rauwolscine	Chemical	D015016
1355091	543	566	Orthostatic hypotension	Disease	D007024
1355091	743	751	prazosin	Chemical	D011224
1355091	774	785	rauwolscine	Chemical	D015016
1355091	839	862	orthostatic hypotension	Disease	D007024
1355091	887	895	prazosin	Chemical	D011224
1355091	947	958	rauwolscine	Chemical	D015016
1355091	1033	1041	prazosin	Chemical	D011224
1355091	1144	1152	prazosin	Chemical	D011224
1355091	1256	1279	orthostatic hypotension	Disease	D007024
1355091	1336	1344	prazosin	Chemical	D011224
1355091	1395	1406	rauwolscine	Chemical	D015016
1355091	1435	1443	prazosin	Chemical	D011224
1355091	1603	1614	bradycardia	Disease	D001919
1355091	1638	1648	cirazoline	Chemical	C014282
1355091	1703	1715	Abbott-53693	Chemical	C056299
1355091	1752	1765	noradrenaline	Chemical	D009638
1355091	1859	1867	prazosin	Chemical	D011224
1355091	1903	1914	bradycardia	Disease	D001919
1355091	1926	1936	cirazoline	Chemical	C014282
1355091	1963	1971	prazosin	Chemical	D011224
1355091	2076	2088	Abbott-53693	Chemical	C056299
1355091	2146	2157	bradycardia	Disease	D001919
1355091	2190	2198	prazosin	Chemical	D011224
1355091	2255	2266	bradycardia	Disease	D001919
1355091	2288	2301	noradrenaline	Chemical	D009638
1355091	2369	2377	prazosin	Chemical	D011224
1355091	CID	D009638	D001919
1355091	CID	D011224	D007024
1355091	CID	C014282	D001919
1355091	CID	C056299	D006973
1355091	CID	D009638	D006973
1355091	CID	C056299	D001919
1355091	CID	C014282	D006973

8638876|t|Coexistence of cerebral venous sinus and internal carotid artery thrombosis associated with exogenous sex hormones. A case report.
8638876|a|A forty-six year-old premenopausal woman developed headache, nausea and vomiting, left hemiparesis and seizure two days after parenteral use of progesterone and estradiol. Diabetes mellitus (DM) was found during admission. Computed tomography showed a hemorrhagic infarct in the right frontal lobe and increased density in the superior sagittal sinus (SSS). Left carotid angiography found occlusion of the left internal carotid artery (ICA). Right carotid angiograms failed to show the SSS and inferior sagittal sinus, suggestive of venous sinus thrombosis. Coexistence of the cerebral artery and the venous sinus occlusion has been described infrequently. In this case, the authors postulate that the use of estradiol and progesterone and the underlying DM increased vascular thrombogenicity, which provided a common denominator for thrombosis of both the ICA and the venous sinus.
8638876	15	75	cerebral venous sinus and internal carotid artery thrombosis	Disease	D012851|D002341	cerebral venous sinus thrombosis|internal carotid artery thrombosis
8638876	182	190	headache	Disease	D006261
8638876	192	198	nausea	Disease	D009325
8638876	203	211	vomiting	Disease	D014839
8638876	218	229	hemiparesis	Disease	D010291
8638876	234	241	seizure	Disease	D012640
8638876	275	287	progesterone	Chemical	D011374
8638876	292	301	estradiol	Chemical	D004958
8638876	303	320	Diabetes mellitus	Disease	D003920
8638876	322	324	DM	Disease	D003920
8638876	383	402	hemorrhagic infarct	Disease	D002543|D002544	hemorrhagic|infarct
8638876	520	565	occlusion of the left internal carotid artery	Disease	D001157
8638876	664	687	venous sinus thrombosis	Disease	D012851
8638876	708	754	cerebral artery and the venous sinus occlusion	Disease	D002544|-1	cerebral artery occlusion|the venous sinus occlusion
8638876	840	849	estradiol	Chemical	D004958
8638876	854	866	progesterone	Chemical	D011374
8638876	886	888	DM	Disease	D003920
8638876	965	1012	thrombosis of both the ICA and the venous sinus	Disease	D002341|D012851	thrombosis of the ICA|thrombosis of the venous sinus
8638876	CID	D004958	D002341
8638876	CID	D004958	D002544
8638876	CID	D011374	D002543
8638876	CID	D011374	D012851
8638876	CID	D004958	D012851
8638876	CID	D011374	D002544
8638876	CID	D004958	D002543
8638876	CID	D011374	D002341

1628552|t|Chloroquine related complete heart block with blindness: case report.
1628552|a|A 27-year old African woman with history of regular chloroquine ingestion presented with progressive deterioration of vision, easy fatiguability, dyspnoea, dizziness progressing to syncopal attacks. Ophthalmological assessment revealed features of chloroquine retinopathy, cardiac assessment revealed features of heart failure and a complete heart block with right bundle branch block pattern. The heart block was treated by pacemaker insertion and the heart failure resolved spontaneously following chloroquine discontinuation. She however remains blind.
1628552	0	11	Chloroquine	Chemical	D002738
1628552	29	40	heart block	Disease	D006327
1628552	46	55	blindness	Disease	D001766
1628552	122	133	chloroquine	Chemical	D002738
1628552	171	194	deterioration of vision	Disease	D015354
1628552	201	214	fatiguability	Disease	D005221
1628552	216	224	dyspnoea	Disease	D004417
1628552	226	235	dizziness	Disease	D004244
1628552	251	267	syncopal attacks	Disease	D013575
1628552	318	329	chloroquine	Chemical	D002738
1628552	330	341	retinopathy	Disease	D012164
1628552	383	396	heart failure	Disease	D006333
1628552	412	423	heart block	Disease	D006327
1628552	429	454	right bundle branch block	Disease	D002037
1628552	468	479	heart block	Disease	D006327
1628552	523	536	heart failure	Disease	D006333
1628552	570	581	chloroquine	Chemical	D002738
1628552	619	624	blind	Disease	D001766
1628552	CID	D002738	D005221
1628552	CID	D002738	D006333
1628552	CID	D002738	D004417
1628552	CID	D002738	D013575
1628552	CID	D002738	D002037
1628552	CID	D002738	D001766
1628552	CID	D002738	D012164
1628552	CID	D002738	D004244

11524350|t|Systemic toxicity and resuscitation in bupivacaine-, levobupivacaine-, or ropivacaine-infused rats.
11524350|a|We compared the systemic toxicity of bupivacaine, levobupivacaine, and ropivacaine in anesthetized rats. We also compared the ability to resuscitate rats after lethal doses of these local anesthetics. Bupivacaine, levobupivacaine, or ropivacaine was infused at a rate of 2 mg. kg(-1). min(-1) while electrocardiogram, electroencephalogram, and arterial pressure were continuously monitored. When asystole was recorded, drug infusion was stopped and a resuscitation sequence was begun. Epinephrine 0.01 mg/kg was administered at 1-min intervals while external cardiac compressions were applied. Resuscitation was considered successful when a systolic arterial pressure > or =100 mm Hg was achieved within 5 min. The cumulative doses of levobupivacaine and ropivacaine that produced seizures were similar and were larger than those of bupivacaine. The cumulative doses of levobupivacaine that produced dysrhythmias and asystole were smaller than the corresponding doses of ropivacaine, but they were larger than those of bupivacaine. The number of successful resuscitations did not differ among groups. However, a smaller dose of epinephrine was required in the Ropivacaine group than in the other groups. We conclude that the systemic toxicity of levobupivacaine is intermediate between that of ropivacaine and bupivacaine when administered at the same rate and that ropivacaine-induced cardiac arrest appears to be more susceptible to treatment than that induced by bupivacaine or levobupivacaine.
11524350	9	17	toxicity	Disease	D064420
11524350	39	50	bupivacaine	Chemical	D002045
11524350	53	68	levobupivacaine	Chemical	C476513
11524350	74	85	ropivacaine	Chemical	C037663
11524350	125	133	toxicity	Disease	D064420
11524350	137	148	bupivacaine	Chemical	D002045
11524350	150	165	levobupivacaine	Chemical	C476513
11524350	171	182	ropivacaine	Chemical	C037663
11524350	301	312	Bupivacaine	Chemical	D002045
11524350	314	329	levobupivacaine	Chemical	C476513
11524350	334	345	ropivacaine	Chemical	C037663
11524350	496	504	asystole	Disease	D006323
11524350	585	596	Epinephrine	Chemical	D004837
11524350	835	850	levobupivacaine	Chemical	C476513
11524350	855	866	ropivacaine	Chemical	C037663
11524350	881	889	seizures	Disease	D012640
11524350	933	944	bupivacaine	Chemical	D002045
11524350	970	985	levobupivacaine	Chemical	C476513
11524350	1000	1012	dysrhythmias	Disease	D001145
11524350	1017	1025	asystole	Disease	D006323
11524350	1071	1082	ropivacaine	Chemical	C037663
11524350	1119	1130	bupivacaine	Chemical	D002045
11524350	1228	1239	epinephrine	Chemical	D004837
11524350	1260	1271	Ropivacaine	Chemical	C037663
11524350	1334	1342	toxicity	Disease	D064420
11524350	1346	1361	levobupivacaine	Chemical	C476513
11524350	1394	1405	ropivacaine	Chemical	C037663
11524350	1410	1421	bupivacaine	Chemical	D002045
11524350	1466	1477	ropivacaine	Chemical	C037663
11524350	1486	1500	cardiac arrest	Disease	D006323
11524350	1566	1577	bupivacaine	Chemical	D002045
11524350	1581	1596	levobupivacaine	Chemical	C476513
11524350	CID	C476513	D001145
11524350	CID	C037663	D012640
11524350	CID	C037663	D006323
11524350	CID	C476513	D012640
11524350	CID	C037663	D001145
11524350	CID	C476513	D006323

10027919|t|22-oxacalcitriol suppresses secondary hyperparathyroidism without inducing low bone turnover in dogs with renal failure.
10027919|a|BACKGROUND: Calcitriol therapy suppresses serum levels of parathyroid hormone (PTH) in patients with renal failure but has several drawbacks, including hypercalcemia and/or marked suppression of bone turnover, which may lead to adynamic bone disease. A new vitamin D analogue, 22-oxacalcitriol (OCT), has been shown to have promising characteristics. This study was undertaken to determine the effects of OCT on serum PTH levels and bone turnover in states of normal or impaired renal function. METHODS: Sixty dogs were either nephrectomized (Nx, N = 38) or sham-operated (Sham, N = 22). The animals received supplemental phosphate to enhance PTH secretion. Fourteen weeks after the start of phosphate supplementation, half of the Nx and Sham dogs received doses of OCT (three times per week); the other half were given vehicle for 60 weeks. Thereafter, the treatment modalities for a subset of animals were crossed over for an additional eight months. Biochemical and hormonal indices of calcium and bone metabolism were measured throughout the study, and bone biopsies were done at baseline, 60 weeks after OCT or vehicle treatment, and at the end of the crossover period. RESULTS: In Nx dogs, OCT significantly decreased serum PTH levels soon after the induction of renal insufficiency. In long-standing secondary hyperparathyroidism, OCT (0.03 microg/kg) stabilized serum PTH levels during the first months. Serum PTH levels rose thereafter, but the rise was less pronounced compared with baseline than the rise seen in Nx control. These effects were accompanied by episodes of hypercalcemia and hyperphosphatemia. In animals with normal renal function, OCT induced a transient decrease in serum PTH levels at a dose of 0.1 microg/kg, which was not sustained with lowering of the doses. In Nx dogs, OCT reversed abnormal bone formation, such as woven osteoid and fibrosis, but did not significantly alter the level of bone turnover. In addition, OCT improved mineralization lag time, (that is, the rate at which osteoid mineralizes) in both Nx and Sham dogs. CONCLUSIONS: These results indicate that even though OCT does not completely prevent the occurrence of hypercalcemia in experimental dogs with renal insufficiency, it may be of use in the management of secondary hyperparathyroidism because it does not induce low bone turnover and, therefore, does not increase the risk of adynamic bone disease.
10027919	0	16	22-oxacalcitriol	Chemical	C051883
10027919	28	57	secondary hyperparathyroidism	Disease	D006962
10027919	75	92	low bone turnover	Disease	D001851
10027919	106	119	renal failure	Disease	D051437
10027919	133	143	Calcitriol	Chemical	D002117
10027919	222	235	renal failure	Disease	D051437
10027919	273	286	hypercalcemia	Disease	D006934
10027919	301	329	suppression of bone turnover	Disease	D001851
10027919	349	370	adynamic bone disease	Disease	D001851
10027919	378	387	vitamin D	Chemical	D014807
10027919	398	414	22-oxacalcitriol	Chemical	C051883
10027919	416	419	OCT	Chemical	C051883
10027919	526	529	OCT	Chemical	C051883
10027919	591	614	impaired renal function	Disease	D007674
10027919	743	752	phosphate	Chemical	D010710
10027919	813	822	phosphate	Chemical	D010710
10027919	887	890	OCT	Chemical	C051883
10027919	1110	1117	calcium	Chemical	D002118
10027919	1230	1233	OCT	Chemical	C051883
10027919	1317	1320	OCT	Chemical	C051883
10027919	1390	1409	renal insufficiency	Disease	D051437
10027919	1428	1457	secondary hyperparathyroidism	Disease	D006962
10027919	1459	1462	OCT	Chemical	C051883
10027919	1703	1716	hypercalcemia	Disease	D006934
10027919	1721	1738	hyperphosphatemia	Disease	D054559
10027919	1779	1782	OCT	Chemical	C051883
10027919	1924	1927	OCT	Chemical	C051883
10027919	1970	1983	woven osteoid	Disease	-1
10027919	1988	1996	fibrosis	Disease	D005355
10027919	2071	2074	OCT	Chemical	C051883
10027919	2237	2240	OCT	Chemical	C051883
10027919	2287	2300	hypercalcemia	Disease	D006934
10027919	2327	2346	renal insufficiency	Disease	D051437
10027919	2386	2415	secondary hyperparathyroidism	Disease	D006962
10027919	2443	2460	low bone turnover	Disease	D001851
10027919	2507	2528	adynamic bone disease	Disease	D001851
10027919	CID	C051883	D006934
10027919	CID	C051883	D054559
10027919	CID	D002117	D001851
10027919	CID	D002117	D006934

8643966|t|Chemotherapy of advanced inoperable non-small cell lung cancer with paclitaxel: a phase II trial.
8643966|a|Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has demonstrated significant antineoplastic activity against different tumor types, notably ovarian and breast carcinoma. Two phase II trials of 24-hour paclitaxel infusions in chemotherapy-naive patients with stage IIIB or IV non-small cell lung cancer (NSCLC) reported response rates of 21% and 24%. Leukopenia was dose limiting: as many as 62.5% of patients experienced grade 4 leukopenia. We investigated the efficacy and toxicity of a 3-hour paclitaxel infusion in a phase II trial in patients with inoperable stage IIIB or IV NSCLC. The 58 patients treated (41 men and 17 women) had a median age of 59 years (age range, 25 to 75) and a performance status of 0 through 2. Most patients (72.4%) had stage IV NSCLC. Paclitaxel 225 mg/m2 was infused over 3 hours every 3 weeks with standard prophylactic premedication. Of 50 patients evaluable for response, 12 (24%) had partial remission, 26 (52%) had no change, and 12 had disease progression (24%). Hematologic toxicities were mild: only one patient (2%) developed grade 3 or 4 neutropenia, while 29% had grade 1 or 2. Grade 1 or 2 polyneuropathy affected 56% of patients while only one (2%) experienced severe polyneuropathy. Similarly, grade 1 or 2 myalgia/arthralgia was observed in 63.2% of patients, but only 14.3% experienced grade 3 or 4. Nausea and vomiting were infrequent, with 14% of patients experiencing grade 1 or 2 and only 2% experiencing grade 3 or 4. Paclitaxel is thus an active single agent in this patient population, with a 3-hour infusion proving comparably effective to a 24-hour infusion and superior in terms of the incidence of hematologic and nonhematologic toxicity. Further phase II studies with paclitaxel combined with other drugs active against NSCLC are indicated, and phase III studies comparing paclitaxel with standard chemotherapy remain to be completed.
8643966	36	62	non-small cell lung cancer	Disease	D002289
8643966	68	78	paclitaxel	Chemical	D017239
8643966	98	108	Paclitaxel	Chemical	D017239
8643966	110	115	Taxol	Chemical	D017239
8643966	233	238	tumor	Disease	D009369
8643966	254	282	ovarian and breast carcinoma	Disease	D010051|D001943	ovarian carcinoma|breast carcinoma
8643966	315	325	paclitaxel	Chemical	D017239
8643966	389	415	non-small cell lung cancer	Disease	D002289
8643966	417	422	NSCLC	Disease	D002289
8643966	464	474	Leukopenia	Disease	D007970
8643966	543	553	leukopenia	Disease	D007970
8643966	588	596	toxicity	Disease	D064420
8643966	609	619	paclitaxel	Chemical	D017239
8643966	694	699	NSCLC	Disease	D002289
8643966	874	879	NSCLC	Disease	D002289
8643966	881	891	Paclitaxel	Chemical	D017239
8643966	1128	1138	toxicities	Disease	D064420
8643966	1195	1206	neutropenia	Disease	D009503
8643966	1249	1263	polyneuropathy	Disease	D011115
8643966	1328	1342	polyneuropathy	Disease	D011115
8643966	1368	1375	myalgia	Disease	D063806
8643966	1376	1386	arthralgia	Disease	D018771
8643966	1463	1469	Nausea	Disease	D009325
8643966	1474	1482	vomiting	Disease	D014839
8643966	1586	1596	Paclitaxel	Chemical	D017239
8643966	1803	1811	toxicity	Disease	D064420
8643966	1843	1853	paclitaxel	Chemical	D017239
8643966	1895	1900	NSCLC	Disease	D002289
8643966	1948	1958	paclitaxel	Chemical	D017239
8643966	CID	D017239	D009325
8643966	CID	D017239	D014839
8643966	CID	D017239	D018771
8643966	CID	D017239	D011115
8643966	CID	D017239	D009503
8643966	CID	D017239	D063806

6695415|t|Cerebral hemorrhage associated with phenylpropanolamine in combination with caffeine.
6695415|a|Phenylpropanolamine (PPA) is a drug that has been associated with serious side effects including stroke. It is often combined with caffeine in diet preparations and "look-alike" pills. In order to determine if PPA/caffeine can lead to stroke in normotensive and/or hypertensive rats, we administered the combination in six times the allowed human dose calculated on a per weight basis for the rats two times per day for five days. Subarachnoid and cerebral hemorrhage was noted in 18% of the hypertensive rats. A single PPA/caffeine administration (same dose) lead to acute hypertension in both the normotensive and hypertensive animals. These results suggest that PPA/caffeine can lead to cerebral hemorrhage in previously hypertensive animals when administered in greater than the allowed dosage. An acute elevation in blood pressure may be a contributing factor.
6695415	0	19	Cerebral hemorrhage	Disease	D002543
6695415	36	55	phenylpropanolamine	Chemical	D010665
6695415	76	84	caffeine	Chemical	D002110
6695415	86	105	Phenylpropanolamine	Chemical	D010665
6695415	107	110	PPA	Chemical	D010665
6695415	183	189	stroke	Disease	D020521
6695415	217	225	caffeine	Chemical	D002110
6695415	296	299	PPA	Chemical	D010665
6695415	300	308	caffeine	Chemical	D002110
6695415	321	327	stroke	Disease	D020521
6695415	351	363	hypertensive	Disease	D006973
6695415	517	553	Subarachnoid and cerebral hemorrhage	Disease	D013345|D002543	Subarachnoid hemorrhage|cerebral hemorrhage
6695415	578	590	hypertensive	Disease	D006973
6695415	606	609	PPA	Chemical	D010665
6695415	610	618	caffeine	Chemical	D002110
6695415	660	672	hypertension	Disease	D006973
6695415	702	714	hypertensive	Disease	D006973
6695415	751	754	PPA	Chemical	D010665
6695415	755	763	caffeine	Chemical	D002110
6695415	776	795	cerebral hemorrhage	Disease	D002543
6695415	810	822	hypertensive	Disease	D006973
6695415	CID	D002110	D006973
6695415	CID	D002110	D013345
6695415	CID	D010665	D013345
6695415	CID	D002110	D002543
6695415	CID	D010665	D006973
6695415	CID	D010665	D002543
6695415	CID	D010665	D020521

6637851|t|Long-term efficacy and toxicity of high-dose amiodarone therapy for ventricular tachycardia or ventricular fibrillation.
6637851|a|Amiodarone was administered to 154 patients who had sustained, symptomatic ventricular tachycardia (VT) (n = 118) or a cardiac arrest (n = 36) and who were refractory to conventional antiarrhythmic drugs. The loading dose was 800 mg/day for 6 weeks and the maintenance dose was 600 mg/day. Sixty-nine percent of patients continued treatment with amiodarone and had no recurrence of symptomatic VT or ventricular fibrillation (VF) over a follow-up of 6 to 52 months (mean +/- standard deviation 14.2 +/- 8.2). Six percent of the patients had a nonfatal recurrence of VT and were successfully managed by continuing amiodarone at a higher dose or by the addition of a conventional antiarrhythmic drug. One or more adverse drug reactions occurred in 51% of patients. Adverse effects forced a reduction in the dose of amiodarone in 41% and discontinuation of amiodarone in 10% of patients. The most common symptomatic adverse reactions were tremor or ataxia (35%), nausea and anorexia (8%), visual halos or blurring (6%), thyroid function abnormalities (6%) and pulmonary interstitial infiltrates (5%). Although large-dose amiodarone is highly effective in the long-term treatment of VT or VF refractory to conventional antiarrhythmic drugs, it causes significant toxicity in approximately 50% of patients. However, when the dose is adjusted based on clinical response or the development of adverse effects, 75% of patients with VT or VF can be successfully managed with amiodarone.
6637851	23	31	toxicity	Disease	D064420
6637851	45	55	amiodarone	Chemical	D000638
6637851	68	91	ventricular tachycardia	Disease	D017180
6637851	95	119	ventricular fibrillation	Disease	D014693
6637851	121	131	Amiodarone	Chemical	D000638
6637851	196	219	ventricular tachycardia	Disease	D017180
6637851	221	223	VT	Disease	D017180
6637851	240	254	cardiac arrest	Disease	D006323
6637851	467	477	amiodarone	Chemical	D000638
6637851	515	517	VT	Disease	D017180
6637851	521	545	ventricular fibrillation	Disease	D014693
6637851	547	549	VF	Disease	D014693
6637851	687	689	VT	Disease	D017180
6637851	734	744	amiodarone	Chemical	D000638
6637851	934	944	amiodarone	Chemical	D000638
6637851	975	985	amiodarone	Chemical	D000638
6637851	1057	1063	tremor	Disease	D014202
6637851	1067	1073	ataxia	Disease	D001259
6637851	1081	1087	nausea	Disease	D009325
6637851	1092	1100	anorexia	Disease	D000855
6637851	1107	1131	visual halos or blurring	Disease	D014786
6637851	1138	1168	thyroid function abnormalities	Disease	D013959
6637851	1178	1212	pulmonary interstitial infiltrates	Disease	-1
6637851	1239	1249	amiodarone	Chemical	D000638
6637851	1300	1302	VT	Disease	D017180
6637851	1306	1308	VF	Disease	D014693
6637851	1380	1388	toxicity	Disease	D064420
6637851	1545	1547	VT	Disease	D017180
6637851	1551	1553	VF	Disease	D014693
6637851	1587	1597	amiodarone	Chemical	D000638
6637851	CID	D000638	D001259
6637851	CID	D000638	D000855
6637851	CID	D000638	D009325
6637851	CID	D000638	D013959
6637851	CID	D000638	D014786

8800187|t|Effect of calcium chloride and 4-aminopyridine therapy on desipramine toxicity in rats.
8800187|a|BACKGROUND: Hypotension is a major contributor to mortality in tricyclic antidepressant overdose. Recent data suggest that tricyclic antidepressants inhibit calcium influx in some tissues. This study addressed the potential role of calcium channel blockade in tricyclic antidepressant-induced hypotension. METHODS: Two interventions were studied that have been shown previously to improve blood pressure with calcium channel blocker overdose. CaCl2 and 4-aminopyridine. Anesthetized rats received the tricyclic antidepressant desipramine IP to produce hypotension, QRS prolongation, and bradycardia. Fifteen min later, animals received CaCl2, NaHCO3, or saline. In a second experiment, rats received tricyclic antidepressant desipramine IP followed in 15 min by 4-aminopyridine or saline. RESULTS: NaHCO3 briefly (5 min) reversed hypotension and QRS prolongation. CaCl2 and 4-aminopyridine failed to improve blood pressure. The incidence of ventricular arrhythmias (p = 0.004) and seizures (p = 0.03) in the CaCl2 group was higher than the other groups. CONCLUSION: The administration of CaCl2 or 4-aminopyridine did not reverse tricyclic antidepressant-induced hypotension in rats. CaCl2 therapy may possibly worsen both cardiovascular and central nervous system toxicity. These findings do not support a role for calcium channel inhibition in the pathogenesis of tricyclic antidepressant-induced hypotension.
8800187	10	26	calcium chloride	Chemical	D002122
8800187	31	46	4-aminopyridine	Chemical	D015761
8800187	58	69	desipramine	Chemical	D003891
8800187	70	78	toxicity	Disease	D064420
8800187	100	111	Hypotension	Disease	D007022
8800187	176	184	overdose	Disease	D062787
8800187	245	252	calcium	Chemical	D002118
8800187	320	327	calcium	Chemical	D002118
8800187	381	392	hypotension	Disease	D007022
8800187	497	504	calcium	Chemical	D002118
8800187	521	529	overdose	Disease	D062787
8800187	531	536	CaCl2	Chemical	D002122
8800187	541	556	4-aminopyridine	Chemical	D015761
8800187	614	625	desipramine	Chemical	D003891
8800187	640	651	hypotension	Disease	D007022
8800187	675	686	bradycardia	Disease	D001919
8800187	724	729	CaCl2	Chemical	D002122
8800187	731	737	NaHCO3	Chemical	D017693
8800187	813	824	desipramine	Chemical	D003891
8800187	850	865	4-aminopyridine	Chemical	D015761
8800187	886	892	NaHCO3	Chemical	D017693
8800187	918	929	hypotension	Disease	D007022
8800187	952	957	CaCl2	Chemical	D002122
8800187	962	977	4-aminopyridine	Chemical	D015761
8800187	1029	1052	ventricular arrhythmias	Disease	D001145
8800187	1069	1077	seizures	Disease	D012640
8800187	1096	1101	CaCl2	Chemical	D002122
8800187	1176	1181	CaCl2	Chemical	D002122
8800187	1185	1200	4-aminopyridine	Chemical	D015761
8800187	1250	1261	hypotension	Disease	D007022
8800187	1271	1276	CaCl2	Chemical	D002122
8800187	1310	1360	cardiovascular and central nervous system toxicity	Disease	D002318|D002493	cardiovascular toxicity|central nervous system toxicity
8800187	1403	1410	calcium	Chemical	D002118
8800187	1486	1497	hypotension	Disease	D007022
8800187	CID	D003891	D007022
8800187	CID	D003891	D001145
8800187	CID	D003891	D001919
8800187	CID	D002122	D001145

7707116|t|Phase I trial of 13-cis-retinoic acid in children with neuroblastoma following bone marrow transplantation.
7707116|a|PURPOSE: Treatment of neuroblastoma cell lines with 13-cis-retinoic acid (cis-RA) can cause sustained inhibition of proliferation. Since cis-RA has demonstrated clinical responses in neuroblastoma patients, it may be effective in preventing relapse after cytotoxic therapy. This phase I trial was designed to determine the maximal-tolerated dosage (MTD), toxicities, and pharmacokinetics of cis-RA administered on an intermittent schedule in children with neuroblastoma following bone marrow transplantation (BMT). PATIENTS AND METHODS: Fifty-one assessable patients, 2 to 12 years of age, were treated with oral cis-RA administered in two equally divided doses daily for 2 weeks, followed by a 2-week rest period, for up to 12 courses. The dose was escalated from 100 to 200 mg/m2/d until dose-limiting toxicity (DLT) was observed. A single intrapatient dose escalation was permitted. RESULTS: The MTD of cis-RA was 160 mg/m2/d. Dose-limiting toxicities in six of nine patients at 200 mg/m2/d included hypercalcemia (n = 3), rash (n = 2), and anemia/thrombocytopenia/emesis/rash (n = 1). All toxicities resolved after cis-RA was discontinued. Three complete responses were observed in marrow metastases. Serum levels of 7.4 +/- 3.0 mumol/L (peak) and 4.0 +/- 2.8 mumol/L (trough) at the MTD were maintained during 14 days of therapy. The DLT correlated with serum levels > or = 10 mumol/L. CONCLUSION: The MTD of cis-RA given on this intermittent schedule was 160 mg/m2/d. Serum levels known to be effective against neuroblastoma in vitro were achieved at this dose. The DLT included hypercalcemia, and may be predicted by serum cis-RA levels. Monitoring of serum calcium and cis-RA levels is indicated in future trials.
7707116	17	37	13-cis-retinoic acid	Chemical	D015474
7707116	55	68	neuroblastoma	Disease	D009447
7707116	130	143	neuroblastoma	Disease	D009447
7707116	160	180	13-cis-retinoic acid	Chemical	D015474
7707116	182	188	cis-RA	Chemical	D015474
7707116	245	251	cis-RA	Chemical	D015474
7707116	291	304	neuroblastoma	Disease	D009447
7707116	463	473	toxicities	Disease	D064420
7707116	499	505	cis-RA	Chemical	D015474
7707116	564	577	neuroblastoma	Disease	D009447
7707116	721	727	cis-RA	Chemical	D015474
7707116	912	920	toxicity	Disease	D064420
7707116	1014	1020	cis-RA	Chemical	D015474
7707116	1052	1062	toxicities	Disease	D064420
7707116	1111	1124	hypercalcemia	Disease	D006934
7707116	1134	1138	rash	Disease	D005076
7707116	1152	1158	anemia	Disease	D000740
7707116	1159	1175	thrombocytopenia	Disease	D013921
7707116	1176	1182	emesis	Disease	D014839
7707116	1183	1187	rash	Disease	D005076
7707116	1201	1211	toxicities	Disease	D064420
7707116	1227	1233	cis-RA	Chemical	D015474
7707116	1301	1311	metastases	Disease	D009362
7707116	1522	1528	cis-RA	Chemical	D015474
7707116	1625	1638	neuroblastoma	Disease	D009447
7707116	1693	1706	hypercalcemia	Disease	D006934
7707116	1738	1744	cis-RA	Chemical	D015474
7707116	1773	1780	calcium	Chemical	D002118
7707116	1785	1791	cis-RA	Chemical	D015474
7707116	CID	D015474	D013921
7707116	CID	D015474	D005076
7707116	CID	D015474	D000740
7707116	CID	D015474	D006934
7707116	CID	D015474	D014839

6892185|t|Effect of calcium chloride on gross behavioural changes produced by carbachol and eserine in cats.
6892185|a|The effect of calcium chloride injected into the cerebral ventricles of group-housed unanaesthetized cats upon vocalization (rage, hissing and snarling), fighting (attack with paws and claws, defense with paws and claws and biting), mydriasis, tremor and clonic-tonic convulsions produced by carbachol and eserine injected similarly was investigated. Calcium chloride depressed or almost completely abolished the vocalization and fighting due to carbachol and eserine. On the other hand, mydriasis, tremor and clonic-tonic convulsions evoked by carbachol and eserine were not significantly changed by calcium chloride. It is apparent that calcium chloride can "dissociate" vocalization and fighting from autonomic and motor phenomena such as mydriasis, tremor and clonic-tonic convulsions caused by carbachol and eserine. Calcium chloride inhibited the vocalization and fighting produced by carbachol and eserine most probably by a nonspecific stabilizing action on central muscarinic cholinoceptive sites. These results further support the view that calcium ions in excess have an atropine-like action also in the central nervous system.
6892185	10	26	calcium chloride	Chemical	D002122
6892185	68	77	carbachol	Chemical	D002217
6892185	82	89	eserine	Chemical	D010830
6892185	113	129	calcium chloride	Chemical	D002122
6892185	332	341	mydriasis	Disease	D015878
6892185	343	349	tremor	Disease	D014202
6892185	354	378	clonic-tonic convulsions	Disease	D004830
6892185	391	400	carbachol	Chemical	D002217
6892185	405	412	eserine	Chemical	D010830
6892185	450	466	Calcium chloride	Chemical	D002122
6892185	545	554	carbachol	Chemical	D002217
6892185	559	566	eserine	Chemical	D010830
6892185	587	596	mydriasis	Disease	D015878
6892185	598	604	tremor	Disease	D014202
6892185	609	633	clonic-tonic convulsions	Disease	D004830
6892185	644	653	carbachol	Chemical	D002217
6892185	658	665	eserine	Chemical	D010830
6892185	700	716	calcium chloride	Chemical	D002122
6892185	738	754	calcium chloride	Chemical	D002122
6892185	841	850	mydriasis	Disease	D015878
6892185	852	858	tremor	Disease	D014202
6892185	863	887	clonic-tonic convulsions	Disease	D004830
6892185	898	907	carbachol	Chemical	D002217
6892185	912	919	eserine	Chemical	D010830
6892185	921	937	Calcium chloride	Chemical	D002122
6892185	990	999	carbachol	Chemical	D002217
6892185	1004	1011	eserine	Chemical	D010830
6892185	1150	1157	calcium	Chemical	D002118
6892185	1181	1189	atropine	Chemical	D001285
6892185	CID	D002217	D015878
6892185	CID	D010830	D015878
6892185	CID	D010830	D014202
6892185	CID	D002217	D014202
6892185	CID	D010830	D004830
6892185	CID	D002217	D004830

6216862|t|Multiple side effects of penicillamine therapy in one patient with rheumatoid arthritis.
6216862|a|Skin rashes, proteinuria, systemic lupus erythematosus, polymyositis and myasthenia gravis have all been recorded as complications of penicillamine therapy in patients with rheumatoid arthritis. A patient who had developed all 5 is now described. The skin lesion resembled elastosis perforans serpiginosa, which has been reported as a rare side effect in patients with Wilson's disease but not in patients with rheumatoid arthritis treated with penicillamine.
6216862	25	38	penicillamine	Chemical	D010396
6216862	67	87	rheumatoid arthritis	Disease	D001172
6216862	89	100	Skin rashes	Disease	D005076
6216862	102	113	proteinuria	Disease	D011507
6216862	115	143	systemic lupus erythematosus	Disease	D008180
6216862	145	157	polymyositis	Disease	D017285
6216862	162	179	myasthenia gravis	Disease	D009157
6216862	223	236	penicillamine	Chemical	D010396
6216862	262	282	rheumatoid arthritis	Disease	D001172
6216862	340	351	skin lesion	Disease	D012871
6216862	362	393	elastosis perforans serpiginosa	Disease	C536202
6216862	458	474	Wilson's disease	Disease	D006527
6216862	500	520	rheumatoid arthritis	Disease	D001172
6216862	534	547	penicillamine	Chemical	D010396
6216862	CID	D010396	D009157
6216862	CID	D010396	D011507
6216862	CID	D010396	D005076
6216862	CID	D010396	D017285
6216862	CID	D010396	D008180

2004|t|Electrocardiographic changes and cardiac arrhythmias in patients receiving psychotropic drugs.
2004|a|Eight patients had cardiac manifestations that were life-threatening in five while taking psychotropic drugs, either phenothiazines or tricyclic antidepressants. Although most patients were receiving several drugs, Mellaril (thioridazine) appeared to be responsible for five cases of ventricular tachycardia, one of which was fatal in a 35 year old woman. Supraventricular tachycardia developed in one patient receiving Thorazine (chlorpromazine). Aventyl (nortriptyline) and Elavil (amitriptyline) each produced left bundle branch block in a 73 year old woman. Electrocardiographic T and U wave abnormalities were present in most patients. The ventricular arrhythmias responded to intravenous administration of lidocaine and to direct current electric shock; ventricular pacing was required in some instances and intravenous administration of propranolol combined with ventricular pacing in one. The tachyarrhythmias generally subsided within 48 hours after administration of the drugs was stopped. Five of the eight patients were 50 years of age or younger; only one clearly had antecedent heart disease. Major cardiac arrhythmias are a potential hazard in patients without heart disease who are receiving customary therapeutic doses of psychotropic drugs. A prospective clinical trial is suggested to quantify the risk of cardiac complications to patients receiving phenothiazines or tricyclic antidepressant drugs.
2004	33	52	cardiac arrhythmias	Disease	D001145
2004	212	226	phenothiazines	Chemical	D010640
2004	310	318	Mellaril	Chemical	D013881
2004	320	332	thioridazine	Chemical	D013881
2004	379	402	ventricular tachycardia	Disease	D017180
2004	451	479	Supraventricular tachycardia	Disease	D013617
2004	515	524	Thorazine	Chemical	D002746
2004	526	540	chlorpromazine	Chemical	D002746
2004	543	550	Aventyl	Chemical	D009661
2004	552	565	nortriptyline	Chemical	D009661
2004	571	577	Elavil	Chemical	D000639
2004	579	592	amitriptyline	Chemical	D000639
2004	608	632	left bundle branch block	Disease	D002037
2004	740	763	ventricular arrhythmias	Disease	D001145
2004	807	816	lidocaine	Chemical	D008012
2004	939	950	propranolol	Chemical	D011433
2004	996	1012	tachyarrhythmias	Disease	D013610
2004	1187	1200	heart disease	Disease	D006331
2004	1208	1227	cardiac arrhythmias	Disease	D001145
2004	1271	1284	heart disease	Disease	D006331
2004	1420	1441	cardiac complications	Disease	D005117
2004	1464	1478	phenothiazines	Chemical	D010640
2004	CID	D013881	D013617
2004	CID	D009661	D002037
2004	CID	D013881	D017180
2004	CID	D000639	D002037

6118280|t|Serotonergic drugs, benzodiazepines and baclofen block muscimol-induced myoclonic jerks in a strain of mice.
6118280|a|In male Swiss mice, muscimol produced myoclonic jerks. A 3 mg/kg (i.p.) dose induced this response in all of the mice tested and the peak response of 73 jerks per min was observed between 27 and 45 min. Increasing the brain serotonin levels by the administration of 5-hydroxytryptophan (80-160 mg/kg) in combination with a peripheral decarboxylase inhibitor resulted in an inhibition of the muscimol effect. However, in a similar experiment l-dopa (80-160 mg/kg) was without effect. In doses of 3-10 mg/kg, the serotonin receptor agonist MK-212 caused a dose-dependent blockade of the response of muscimol. Of the benzodiazepines, clonazepam (0.1-0.3 mg/kg) was found to be several fold more potent than diazepam (0.3-3 mg/kg) in blocking the myoclonic jerks. While (-)-baclofen (1-3 mg/kg) proved to be an effective antagonist of muscimol, its (+)-isomer (5-20 mg/kg) lacked this property. Considering the fact that 5-HTP and the benzodiazepines have been found to be beneficial in the management of clinical myoclonus, the muscimol-induced myoclonus seems to be a satisfactory animal model that may prove useful for the development of new drug treatments for this condition. Our present study indicated the possible value of MK-212 and (-)-baclofen in the management of clinical myoclonus.
6118280	20	35	benzodiazepines	Chemical	D001569
6118280	40	48	baclofen	Chemical	D001418
6118280	55	63	muscimol	Chemical	D009118
6118280	72	87	myoclonic jerks	Disease	D009207
6118280	129	137	muscimol	Chemical	D009118
6118280	147	162	myoclonic jerks	Disease	D009207
6118280	333	342	serotonin	Chemical	D012701
6118280	375	394	5-hydroxytryptophan	Chemical	D006916
6118280	500	508	muscimol	Chemical	D009118
6118280	550	556	l-dopa	Chemical	D007980
6118280	620	629	serotonin	Chemical	D012701
6118280	647	653	MK-212	Chemical	C014896
6118280	706	714	muscimol	Chemical	D009118
6118280	723	738	benzodiazepines	Chemical	D001569
6118280	740	750	clonazepam	Chemical	D002998
6118280	813	821	diazepam	Chemical	D003975
6118280	852	867	myoclonic jerks	Disease	D009207
6118280	879	887	baclofen	Chemical	D001418
6118280	940	948	muscimol	Chemical	D009118
6118280	1026	1031	5-HTP	Chemical	D006916
6118280	1040	1055	benzodiazepines	Chemical	D001569
6118280	1119	1128	myoclonus	Disease	D009207
6118280	1134	1142	muscimol	Chemical	D009118
6118280	1151	1160	myoclonus	Disease	D009207
6118280	1336	1342	MK-212	Chemical	C014896
6118280	1351	1359	baclofen	Chemical	D001418
6118280	1390	1399	myoclonus	Disease	D009207
6118280	CID	D009118	D009207

3703509|t|Hyperglycemic acidotic coma and death in Kearns-Sayre syndrome.
3703509|a|This paper presents the clinical and metabolic findings in two young boys with long-standing Kearns-Sayre syndrome. Following short exposure to oral prednisone, both boys developed lethargy, increasing somnolence, polydipsia, polyphagia, and polyuria. Both presented in the emergency room with profound coma, hypotension, severe hyperglycemia, and acidosis. Nonketotic lactic acidosis was present in one and ketosis without a known serum lactate level was present in the other. Respiratory failure rapidly ensued and both patients expired in spite of efforts at resuscitation. We believe these two cases represent a newly described and catastrophic metabolic-endocrine failure in the Kearns-Sayre syndrome.
3703509	0	27	Hyperglycemic acidotic coma	Disease	D006943|D000140|D003128	Hyperglycemic|acidotic|coma
3703509	41	62	Kearns-Sayre syndrome	Disease	D007625
3703509	157	178	Kearns-Sayre syndrome	Disease	D007625
3703509	213	223	prednisone	Chemical	D011241
3703509	245	253	lethargy	Disease	D053609
3703509	266	276	somnolence	Disease	D006970
3703509	278	288	polydipsia	Disease	D059606
3703509	290	300	polyphagia	Disease	D006963
3703509	306	314	polyuria	Disease	D011141
3703509	367	371	coma	Disease	D003128
3703509	373	384	hypotension	Disease	D007022
3703509	393	406	hyperglycemia	Disease	D006943
3703509	412	420	acidosis	Disease	D000138
3703509	433	448	lactic acidosis	Disease	D000140
3703509	472	479	ketosis	Disease	D007662
3703509	502	509	lactate	Chemical	D019344
3703509	542	561	Respiratory failure	Disease	D012131
3703509	713	740	metabolic-endocrine failure	Disease	-1
3703509	748	769	Kearns-Sayre syndrome	Disease	D007625
3703509	CID	D011241	D007662
3703509	CID	D011241	D007022
3703509	CID	D011241	D003128
3703509	CID	D011241	D000140
3703509	CID	D011241	D006943

20683499|t|Effects of active constituents of Crocus sativus L., crocin on streptozocin-induced model of sporadic Alzheimer's disease in male rats.
20683499|a|BACKGROUND: The involvement of water-soluble carotenoids, crocins, as the main and active components of Crocus sativus L. extract in learning and memory processes has been proposed. In the present study, the effect of crocins on sporadic Alzheimer's disease induced by intracerebroventricular (icv) streptozocin (STZ) in male rats was investigated. METHODS: Male adult Wistar rats (n = 90 and 260-290 g) were divided into 1, control; 2 and 3, crocins (15 and 30 mg/kg); 4, STZ; 5 and 6, STZ + crocins (15 and 30 mg/kg) groups. In Alzheimer's disease groups, rats were injected with STZ-icv bilaterally (3 mg/kg) in first day and 3 days later, a similar STZ-icv application was repeated. In STZ + crocin animal groups, crocin was applied in doses of 15 and 30 mg/kg, i.p., one day pre-surgery and continued for three weeks. Prescription of crocin in each dose was repeated once for two days. However, the learning and memory performance was assessed using passive avoidance paradigm, and for spatial cognition evaluation, Y-maze task was used. RESULTS: It was found out that crocin (30 mg/kg)-treated STZ-injected rats show higher correct choices and lower errors in Y-maze than vehicle-treated STZ-injected rats. In addition, crocin in the mentioned dose could significantly attenuated learning and memory impairment in treated STZ-injected group in passive avoidance test. CONCLUSION: Therefore, these results demonstrate the effectiveness of crocin (30 mg/kg) in antagonizing the cognitive deficits caused by STZ-icv in rats and its potential in the treatment of neurodegenerative diseases such as Alzheimer's disease.
20683499	53	59	crocin	Chemical	C029036
20683499	63	75	streptozocin	Chemical	D013311
20683499	102	121	Alzheimer's disease	Disease	D000544
20683499	181	192	carotenoids	Chemical	D002338
20683499	194	201	crocins	Chemical	C029036
20683499	354	361	crocins	Chemical	C029036
20683499	374	393	Alzheimer's disease	Disease	D000544
20683499	435	447	streptozocin	Chemical	D013311
20683499	449	452	STZ	Chemical	D013311
20683499	579	586	crocins	Chemical	C029036
20683499	609	612	STZ	Chemical	D013311
20683499	623	626	STZ	Chemical	D013311
20683499	629	636	crocins	Chemical	C029036
20683499	666	685	Alzheimer's disease	Disease	D000544
20683499	718	721	STZ	Chemical	D013311
20683499	789	792	STZ	Chemical	D013311
20683499	826	829	STZ	Chemical	D013311
20683499	832	838	crocin	Chemical	C029036
20683499	854	860	crocin	Chemical	C029036
20683499	975	981	crocin	Chemical	C029036
20683499	1210	1216	crocin	Chemical	C029036
20683499	1236	1239	STZ	Chemical	D013311
20683499	1330	1333	STZ	Chemical	D013311
20683499	1362	1368	crocin	Chemical	C029036
20683499	1422	1452	learning and memory impairment	Disease	D007859|D008569	learning impairment|memory impairment
20683499	1464	1467	STZ	Chemical	D013311
20683499	1580	1586	crocin	Chemical	C029036
20683499	1618	1636	cognitive deficits	Disease	D003072
20683499	1647	1650	STZ	Chemical	D013311
20683499	1701	1727	neurodegenerative diseases	Disease	D019636
20683499	1736	1755	Alzheimer's disease	Disease	D000544
20683499	CID	D013311	D003072
20683499	CID	D013311	D000544

20466178|t|Rosaceiform dermatitis associated with topical tacrolimus treatment.
20466178|a|We describe herein 3 patients who developed rosacea-like dermatitis eruptions while using 0.03% or 0.1% tacrolimus ointment for facial dermatitis. Skin biopsy specimens showed telangiectasia and noncaseating epithelioid granulomatous tissue formation in the papillary to mid dermis. Continuous topical use of immunomodulators such as tacrolimus or pimecrolimus should be regarded as a potential cause of rosaceiform dermatitis, although many cases have not been reported.
20466178	12	22	dermatitis	Disease	D003872
20466178	47	57	tacrolimus	Chemical	D016559
20466178	113	120	rosacea	Disease	D012393
20466178	126	136	dermatitis	Disease	D003872
20466178	137	146	eruptions	Disease	D003875
20466178	173	183	tacrolimus	Chemical	D016559
20466178	197	214	facial dermatitis	Disease	D005148
20466178	245	259	telangiectasia	Disease	D013684
20466178	403	413	tacrolimus	Chemical	D016559
20466178	417	429	pimecrolimus	Chemical	C117268
20466178	485	495	dermatitis	Disease	D003872
20466178	CID	C117268	D003872
20466178	CID	C117268	D003875
20466178	CID	C117268	D013684

19944736|t|A novel animal model to evaluate the ability of a drug delivery system to promote the passage through the BBB.
19944736|a|The purpose of this investigation was to explore the potentiality of a novel animal model to be used for the in vivo evaluation of the ability of a drug delivery system to promote the passage through the blood-brain barrier (BBB) and/or to improve the brain localization of a bioactive compound. A Tween 80-coated poly-L-lactid acid nanoparticles was used as a model of colloidal drug delivery system, able to trespass the BBB. Tacrine, administered in LiCl pre-treated rats, induces electrocorticographic seizures and delayed hippocampal damage. The toxic effects of tacrine-loaded poly-L-lactid acid nanoparticles (5mg/kg), a saline solution of tacrine (5mg/kg) and an empty colloidal nanoparticle suspension were compared following i.p. administration in LiCl-pre-treated Wistar rats. All the animals treated with tacrine-loaded nanoparticles showed an earlier outcome of CNS adverse symptoms, i.e. epileptic onset, with respect to those animals treated with the free compound (10 min vs. 22 min respectively). In addition, tacrine-loaded nanoparticles administration induced damage of neuronal cells in CA1 field of the hippocampus in all treated animals, while the saline solution of tacrine only in 60% of animals. Empty nanoparticles provided similar results to control (saline-treated) group of animals. In conclusion, the evaluation of time-to-onset of symptoms and the severity of neurodegenerative processes induced by the tacrine-lithium model of epilepsy in the rat, could be used to evaluate preliminarily the capability of a drug delivery system to trespass (or not) the BBB in vivo.
19944736	425	443	poly-L-lactid acid	Chemical	-1
19944736	539	546	Tacrine	Chemical	D013619
19944736	564	568	LiCl	Chemical	D018021
19944736	617	625	seizures	Disease	D012640
19944736	638	656	hippocampal damage	Disease	D001930
19944736	679	686	tacrine	Chemical	D013619
19944736	694	712	poly-L-lactid acid	Chemical	-1
19944736	758	765	tacrine	Chemical	D013619
19944736	869	873	LiCl	Chemical	D018021
19944736	928	935	tacrine	Chemical	D013619
19944736	1013	1022	epileptic	Disease	D004827
19944736	1138	1145	tacrine	Chemical	D013619
19944736	1190	1214	damage of neuronal cells	Disease	D001930
19944736	1300	1307	tacrine	Chemical	D013619
19944736	1545	1552	tacrine	Chemical	D013619
19944736	1553	1560	lithium	Chemical	D008094
19944736	1570	1578	epilepsy	Disease	D004827
19944736	CID	D018021	D001930
19944736	CID	D013619	D001930
19944736	CID	D018021	D012640
19944736	CID	D013619	D012640

19721134|t|The antiarrhythmic effect and possible ionic mechanisms of pilocarpine on animal models.
19721134|a|This study was designed to evaluate the effects of pilocarpine and explore the underlying ionic mechanism, using both aconitine-induced rat and ouabain-induced guinea pig arrhythmia models. Confocal microscopy was used to measure intracellular free-calcium concentrations ([Ca(2+)](i)) in isolated myocytes. The current data showed that pilocarpine significantly delayed onset of arrhythmias, decreased the time course of ventricular tachycardia and fibrillation, reduced arrhythmia score, and increased the survival time of arrhythmic rats and guinea pigs. [Ca(2+)](i) overload induced by aconitine or ouabain was reduced in isolated myocytes pretreated with pilocarpine. Moreover, M(3)-muscarinic acetylcholine receptor (mAChR) antagonist 4-DAMP (4-diphenylacetoxy-N-methylpiperidine-methiodide) partially abolished the beneficial effects of pilocarpine. These data suggest that pilocarpine produced antiarrhythmic actions on arrhythmic rat and guinea pig models induced by aconitine or ouabain via stimulating the cardiac M(3)-mAChR. The mechanism may be related to the improvement of Ca(2+) handling.
19721134	59	70	pilocarpine	Chemical	D010862
19721134	140	151	pilocarpine	Chemical	D010862
19721134	207	216	aconitine	Chemical	D000157
19721134	233	240	ouabain	Chemical	D010042
19721134	260	270	arrhythmia	Disease	D001145
19721134	338	345	calcium	Chemical	D002118
19721134	363	365	Ca	Chemical	D002118
19721134	426	437	pilocarpine	Chemical	D010862
19721134	469	480	arrhythmias	Disease	D001145
19721134	511	551	ventricular tachycardia and fibrillation	Disease	D017180|D014693	ventricular tachycardia|ventricular fibrillation
19721134	561	571	arrhythmia	Disease	D001145
19721134	614	624	arrhythmic	Disease	D001145
19721134	648	650	Ca	Chemical	D002118
19721134	679	688	aconitine	Chemical	D000157
19721134	692	699	ouabain	Chemical	D010042
19721134	749	760	pilocarpine	Chemical	D010862
19721134	788	801	acetylcholine	Chemical	D000109
19721134	830	836	4-DAMP	Chemical	C042375
19721134	838	885	4-diphenylacetoxy-N-methylpiperidine-methiodide	Chemical	C042375
19721134	933	944	pilocarpine	Chemical	D010862
19721134	970	981	pilocarpine	Chemical	D010862
19721134	1017	1027	arrhythmic	Disease	D001145
19721134	1065	1074	aconitine	Chemical	D000157
19721134	1078	1085	ouabain	Chemical	D010042
19721134	1177	1179	Ca	Chemical	D002118
19721134	CID	D010042	D001145
19721134	CID	D000157	D001145

17786501|t|Disulfiram-induced transient optic and peripheral neuropathy: a case report.
17786501|a|AIM: To report a case of optic and peripheral neuropathy after chronic use of disulfiram for alcohol dependence management. MATERIALS AND METHODS: A case report. RESULTS: A 57-year-old male presented with gradual loss of vision in both eyes with intermittent headaches for 2 months. He also complained of paraesthesia with numbness in both feet. His vision was 6/15 and 2/60 in the right and left eyes, respectively. Fundoscopy revealed bilaterally swollen optic nerve heads. Visual field testing confirmed bilateral central-caecal scotomata. He had been taking disulfiram for alcohol dependence for the preceding 3 years. Disulfiram discontinuation lead to an immediate symptomatic improvement. CONCLUSION: Physicians initiating long-term disulfiram therapy should be aware of these adverse effects. They should recommend annual ophthalmic reviews with visual field testing. Patients should be reassured with respect to the reversibility of these adverse effects.
17786501	0	10	Disulfiram	Chemical	D004221
17786501	29	60	optic and peripheral neuropathy	Disease	D009901|D010523	optic neuropathy|peripheral neuropathy
17786501	102	133	optic and peripheral neuropathy	Disease	D009901|D010523	optic neuropathy|peripheral neuropathy
17786501	155	165	disulfiram	Chemical	D004221
17786501	170	188	alcohol dependence	Disease	D000437
17786501	290	304	loss of vision	Disease	D014786
17786501	336	345	headaches	Disease	D006261
17786501	382	394	paraesthesia	Disease	D010292
17786501	400	408	numbness	Disease	D006987
17786501	609	618	scotomata	Disease	D012607
17786501	639	649	disulfiram	Chemical	D004221
17786501	654	672	alcohol dependence	Disease	D000437
17786501	700	710	Disulfiram	Chemical	D004221
17786501	817	827	disulfiram	Chemical	D004221
17786501	CID	D004221	D010292
17786501	CID	D004221	D009901
17786501	CID	D004221	D012607

16960342|t|Sustained clinical improvement of a patient with decompensated hepatitis B virus-related cirrhosis after treatment with lamivudine monotherapy.
16960342|a|Hepatitis B virus (HBV) infection, which causes liver cirrhosis and hepatocellular carcinoma, remains a major health problem in Asian countries. Recent development of vaccine for prevention is reported to be successful in reducing the size of chronically infected carriers, although the standard medical therapies have not been established up to now. In this report, we encountered a patient with decompensated HBV-related cirrhosis who exhibited the dramatic improvements after antiviral therapy. The patient was a 50-year-old woman. Previous conventional medical treatments were not effective for this patient, thus this patient had been referred to our hospital. However, the administration of lamivudine, a reverse transcriptase inhibitor, for 23 months dramatically improved her liver severity. During this period, no drug resistant mutant HBV emerged, and the serum HBV-DNA level was continuously suppressed. These virological responses were also maintained even after the antiviral therapy was discontinued. Moreover, both hepatitis B surface antigen and e antigen were observed to have disappeared in this patient. The administration of lamivudine to patients with HBV-related cirrhosis, like our present case, should be considered as an initial medical therapeutic option, especially in countries where liver transplantation is not reliably available.
16960342	63	74	hepatitis B	Disease	D006509
16960342	89	98	cirrhosis	Disease	D005355
16960342	120	130	lamivudine	Chemical	D019259
16960342	144	177	Hepatitis B virus (HBV) infection	Disease	D006509
16960342	192	207	liver cirrhosis	Disease	D008103
16960342	212	236	hepatocellular carcinoma	Disease	D006528
16960342	567	576	cirrhosis	Disease	D005355
16960342	841	851	lamivudine	Chemical	D019259
16960342	1174	1215	hepatitis B surface antigen and e antigen	Chemical	D006514|D006513	hepatitis B surface antigen|hepatitis B e antigen
16960342	1289	1299	lamivudine	Chemical	D019259
16960342	1329	1338	cirrhosis	Disease	D005355
16960342	CID	D006514	D006509
16960342	CID	D006513	D006509

11226639|t|Dual effects of melatonin on barbiturate-induced narcosis in rats.
11226639|a|Melatonin affects the circadian sleep/wake cycle, but it is not clear whether it may influence drug-induced narcosis. Sodium thiopenthal was administered intraperitoneally into male rats pre-treated with melatonin (0.05, 0.5, 5 and 50 mg/kg). Melatonin pre-treatment affected in a dual manner barbiturate narcosis, however, no dose-effect correlation was found. In particular, low doses reduced the latency to and prolonged the duration of barbiturate narcosis. In contrast, the highest dose of melatonin (50 mg/kg) caused a paradoxical increase in the latency and produced a sustained reduction of the duration of narcosis, and a reduction in mortality rate. Melatonin 0.5 and 5 mg/kg influenced the duration but not the latency of ketamine- or diazepam-induced narcosis. Thus, the dual action of melatonin on pharmacological narcosis seems to be specific for the barbiturate mechanism of action.
11226639	16	25	melatonin	Chemical	D008550
11226639	29	40	barbiturate	Chemical	C032232
11226639	49	57	narcosis	Disease	D053608
11226639	67	76	Melatonin	Chemical	D008550
11226639	175	183	narcosis	Disease	D053608
11226639	185	203	Sodium thiopenthal	Chemical	D013874
11226639	271	280	melatonin	Chemical	D008550
11226639	310	319	Melatonin	Chemical	D008550
11226639	360	371	barbiturate	Chemical	C032232
11226639	372	380	narcosis	Disease	D053608
11226639	507	518	barbiturate	Chemical	C032232
11226639	519	527	narcosis	Disease	D053608
11226639	562	571	melatonin	Chemical	D008550
11226639	682	690	narcosis	Disease	D053608
11226639	727	736	Melatonin	Chemical	D008550
11226639	800	808	ketamine	Chemical	D007649
11226639	813	821	diazepam	Chemical	D003975
11226639	830	838	narcosis	Disease	D053608
11226639	865	874	melatonin	Chemical	D008550
11226639	894	902	narcosis	Disease	D053608
11226639	932	943	barbiturate	Chemical	C032232
11226639	CID	D013874	D053608
11226639	CID	D008550	D053608
11226639	CID	D003975	D053608
11226639	CID	D007649	D053608

9228650|t|Effects of NIK-247 on cholinesterase and scopolamine-induced amnesia.
9228650|a|The effects of NIK-247 on cholinesterase, scopolamine-induced amnesia and spontaneous movement were examined and compared with those of the well-known cholinesterase inhibitors tacrine and E-2020. NIK-247, tacrine and E-2020 all strongly inhibited acetylcholinesterase (AChE) in human red blood cells (IC50s = 1.0 x 10(-6), 2.9 x 10(-7) and 3.7 x 10(-8) M, respectively). In addition, NIK-247 and tacrine, but not E-2020, strongly inhibited butyrylcholinestrase (BuChE) in human serum. All three drugs produced mixed inhibition of AChE activity. Moreover, the inhibitory effect of NIK-247 on AChE was reversible. All compounds at 0.1-1 mg/kg p.o. significantly improved the amnesia induced by scopolamine (0.5 mg/kg s.c.) in rats performing a passive avoidance task. The three compounds at 1 and 3 mg/kg p.o. did not significantly decrease spontaneous movement by rats. These findings suggest that NIK-247 at a low dose (0.1-1 mg/kg p.o.) improves scopolamine-induced amnesia but does not affect spontaneous movement. The findings suggest that NIK-247 may be a useful drug for the treatment of Alzheimer's disease.
9228650	11	18	NIK-247	Chemical	C049860
9228650	41	52	scopolamine	Chemical	D012601
9228650	61	68	amnesia	Disease	D000647
9228650	85	92	NIK-247	Chemical	C049860
9228650	112	123	scopolamine	Chemical	D012601
9228650	132	139	amnesia	Disease	D000647
9228650	247	254	tacrine	Chemical	D013619
9228650	259	265	E-2020	Chemical	C076946
9228650	267	274	NIK-247	Chemical	C049860
9228650	276	283	tacrine	Chemical	D013619
9228650	288	294	E-2020	Chemical	C076946
9228650	455	462	NIK-247	Chemical	C049860
9228650	467	474	tacrine	Chemical	D013619
9228650	484	490	E-2020	Chemical	C076946
9228650	651	658	NIK-247	Chemical	C049860
9228650	744	751	amnesia	Disease	D000647
9228650	763	774	scopolamine	Chemical	D012601
9228650	968	975	NIK-247	Chemical	C049860
9228650	1018	1029	scopolamine	Chemical	D012601
9228650	1038	1045	amnesia	Disease	D000647
9228650	1114	1121	NIK-247	Chemical	C049860
9228650	1164	1183	Alzheimer's disease	Disease	D000544
9228650	CID	C076946	D000647
9228650	CID	C049860	D000647
9228650	CID	D013619	D000647
9228650	CID	D012601	D000647

8766220|t|Nightmares and hallucinations after long-term intake of tramadol combined with antidepressants.
8766220|a|Tramadol is a weak opioid with effects on adrenergic and serotonergic neurotransmission that is used to treat cancer pain and chronic non malignant pain. This drug was initiated in association with paroxetine and dosulepine hydrochloride in a tetraparetic patient with chronic pain. Fifty-six days after initiation of the treatment the patient presented hallucinations that only stopped after the withdrawal of psycho-active drugs and tramadol. The case report questions the long term use of pain killers combined with psycho-active drugs in chronic non malignant pain, especially if pain is under control.
8766220	15	29	hallucinations	Disease	D006212
8766220	56	64	tramadol	Chemical	D014147
8766220	96	104	Tramadol	Chemical	D014147
8766220	206	212	cancer	Disease	D009369
8766220	213	217	pain	Disease	D010146
8766220	244	248	pain	Disease	D010146
8766220	294	304	paroxetine	Chemical	D017374
8766220	309	333	dosulepine hydrochloride	Chemical	D004308
8766220	339	351	tetraparetic	Disease	-1
8766220	365	377	chronic pain	Disease	D059350
8766220	450	464	hallucinations	Disease	D006212
8766220	531	539	tramadol	Chemical	D014147
8766220	588	592	pain	Disease	D010146
8766220	660	664	pain	Disease	D010146
8766220	680	684	pain	Disease	D010146
8766220	CID	D017374	D006212
8766220	CID	D014147	D006212
8766220	CID	D004308	D006212

8441146|t|Apparent cure of rheumatoid arthritis by bone marrow transplantation.
8441146|a|We describe the induction of sustained remissions and possible cure of severe erosive rheumatoid arthritis (RA) by bone marrow transplantation (BMT) in 2 patients. BMT was used to treat severe aplastic anemia which was caused by gold in one case and D-penicillamine in the other. In the 8 and 6 years since the transplants (representing 8 and 4 years since cessation of all immunosuppressive therapy, respectively), the RA in each case has been completely quiescent. Although short term remission of severe RA following BMT has been reported, these are the first cases for which prolonged followup has been available. This experience raises the question of the role of BMT itself as a therapeutic option for patients with uncontrolled destructive synovitis.
8441146	17	37	rheumatoid arthritis	Disease	D001172
8441146	156	176	rheumatoid arthritis	Disease	D001172
8441146	178	180	RA	Disease	D001172
8441146	263	278	aplastic anemia	Disease	D000741
8441146	299	303	gold	Chemical	D006046
8441146	320	335	D-penicillamine	Chemical	D010396
8441146	490	492	RA	Disease	D001172
8441146	577	579	RA	Disease	D001172
8441146	817	826	synovitis	Disease	D013585
8441146	CID	D006046	D000741
8441146	CID	D010396	D000741

3653576|t|Urinary enzymes and protein patterns as indicators of injury to different regions of the kidney.
3653576|a|Acute experimental models of renal damage to the proximal tubular, glomerular, and papillary regions of the rat were produced by administration of hexachloro-1:3-butadiene (HCBD), puromycin aminonucleoside (PAN), and 2-bromoethylamine (BEA), respectively. Several routine indicators of nephrotoxicity, the enzymes alkaline phosphatase and N-acetyl-beta-glucosaminidase, and the molecular weight of protein excretion were determined on urine samples. Tubular damage produced by HCBD or BEA was discriminated both quantitatively and qualitatively from glomerular damage produced by PAN. The latter was characterized by a pronounced increase in protein excretion, especially proteins with molecular weight greater than 40,000 Da. In contrast, protein excretion in tubular damage was raised only slightly and characterized by excretion of proteins of a wide range of molecular weights. Proximal tubular damage caused by HCBD and papillary damage caused by BEA were distinguished both by conventional urinalysis (volume and specific gravity) and by measurement of the two urinary enzymes. Alkaline phosphatase and glucose were markedly and transiently elevated in proximal tubular damage and N-acetyl-beta-glucosaminidase showed a sustained elevation in papillary damage. It is concluded that both selective urinary enzymes and the molecular weight pattern of urinary proteins can be used to provide diagnostic information about the possible site of renal damage.
3653576	54	95	injury to different regions of the kidney	Disease	D007674
3653576	97	138	Acute experimental models of renal damage	Disease	D058186
3653576	244	268	hexachloro-1:3-butadiene	Chemical	C001335
3653576	270	274	HCBD	Chemical	C001335
3653576	277	302	puromycin aminonucleoside	Chemical	D011692
3653576	304	307	PAN	Chemical	D011692
3653576	314	331	2-bromoethylamine	Chemical	C004504
3653576	333	336	BEA	Chemical	C004504
3653576	383	397	nephrotoxicity	Disease	D007674
3653576	495	512	protein excretion	Disease	D011507
3653576	574	578	HCBD	Chemical	C001335
3653576	582	585	BEA	Chemical	C004504
3653576	647	664	glomerular damage	Disease	D007674
3653576	677	680	PAN	Chemical	D011692
3653576	739	756	protein excretion	Disease	D011507
3653576	837	854	protein excretion	Disease	D011507
3653576	919	940	excretion of proteins	Disease	D011507
3653576	1013	1017	HCBD	Chemical	C001335
3653576	1049	1052	BEA	Chemical	C004504
3653576	1206	1213	glucose	Chemical	D005947
3653576	1542	1554	renal damage	Disease	D007674
3653576	CID	D011692	D058186
3653576	CID	D011692	D011507
3653576	CID	C004504	D058186
3653576	CID	C001335	D058186

2750819|t|Neuromuscular blockade with magnesium sulfate and nifedipine.
2750819|a|A patient who received tocolysis with nifedipine developed neuromuscular blockade after 500 mg of magnesium sulfate was administered. This reaction demonstrates that nifedipine can seriously potentiate the toxicity of magnesium. Caution should be exercised when these two tocolytics are combined.
2750819	0	22	Neuromuscular blockade	Disease	D020879
2750819	28	45	magnesium sulfate	Chemical	D008278
2750819	50	60	nifedipine	Chemical	D009543
2750819	100	110	nifedipine	Chemical	D009543
2750819	121	143	neuromuscular blockade	Disease	D020879
2750819	160	177	magnesium sulfate	Chemical	D008278
2750819	228	238	nifedipine	Chemical	D009543
2750819	268	276	toxicity	Disease	D064420
2750819	280	289	magnesium	Chemical	D008274
2750819	CID	D008278	D020879
2750819	CID	D009543	D020879

1899352|t|Ifosfamide continuous infusion without mesna. A phase I trial of a 14-day cycle.
1899352|a|Twenty patients received 27 courses of ifosfamide administered as a 24-hour continuous infusion for 14 days without Mesna. The goal of the study was to deliver a dose rate and total cumulative dose of ifosfamide that would be comparable to standard bolus or short-term infusions administered with Mesna. Dose escalations proceeded from 200 to 300, 400, 450, 500, and 550 mg/m2/d. Four patients developed transient microscopic hematuria at 400, 450, and 500 mg/m2/d. There were no instances of macroscopic hematuria. At 550 mg/m2/d, three patients experienced nonurologic toxicity; confusion (1), nausea (1), and Grade 2 leukopenia (1). The recommended dose of 500 mg/m2/d delivers a total dose of 7 g/m2 per cycle, which is comparable to that delivered in clinical practice for bolus or short-term infusion. Because few patients received multiple courses over time, the cumulative effects are indeterminate in the present trial. The frequency and predictability of hematuria are not precise, and at least daily monitoring by urine Hematest is essential, adding Mesna to the infusate in patients with persistent hematuria. The protracted infusion schedule for ifosfamide permits convenient outpatient administration without Mesna and reduces the drug cost of clinical usage of this agent by up to  890 per cycle. Clinical activity was demonstrated in a single patient, but a comparative trial of standard bolus schedules with the protracted infusion schedule will be necessary to determine if the clinical effectiveness of the drug is maintained.
1899352	0	10	Ifosfamide	Chemical	D007069
1899352	39	44	mesna	Chemical	D015080
1899352	120	130	ifosfamide	Chemical	D007069
1899352	197	202	Mesna	Chemical	D015080
1899352	282	292	ifosfamide	Chemical	D007069
1899352	378	383	Mesna	Chemical	D015080
1899352	507	516	hematuria	Disease	D006417
1899352	586	595	hematuria	Disease	D006417
1899352	652	660	toxicity	Disease	D064420
1899352	662	671	confusion	Disease	D003221
1899352	677	683	nausea	Disease	D009325
1899352	701	711	leukopenia	Disease	D007970
1899352	1046	1055	hematuria	Disease	D006417
1899352	1142	1147	Mesna	Chemical	D015080
1899352	1192	1201	hematuria	Disease	D006417
1899352	1240	1250	ifosfamide	Chemical	D007069
1899352	1304	1309	Mesna	Chemical	D015080
1899352	CID	D007069	D006417
1899352	CID	D007069	D007970
1899352	CID	D007069	D003221
1899352	CID	D007069	D009325

18161408|t|Myocardial infarction in pregnancy associated with clomiphene citrate for ovulation induction: a case report.
18161408|a|BACKGROUND: Clomiphene citrate (CC) is commonly prescribed for ovulation induction. It is considered safe, with minimal side effects. Thromboembolism is a rare but life-threatening complication that has been reported after ovulation induction with CC. Spontaneous coronary thrombosis or thromboembolism with subsequent clot lysis has been suggested as one of the most common causes of myocardial infarction (MI) during pregnancy, with a subsequently normal coronary angiogram. CASE: A 33-year-old woman with a 5-week gestation had recently received CC for ovulation induction and presented with chest pain. An electrocardiogram showed a lateral and anterior wall myocardial infarction. Cardiac enzymes showed a peak rise in troponin I to 9.10 ng/mL. An initial exercise stress test was normal. At the time of admission, the patient was at high risk of radiation injury to the fetus, so a coronary angiogram was postponed until the second trimester. It showed normal coronary vessels. CONCLUSION: This appears to be the first reported case documenting a possible association between CC and myocardial infarction. Thrombosis might be a rare but hazardous complication of CC. Given this life-threatening complication, appropriate prophylactic measures should be used in high-risk woman undergoing ovarian stimulation.
18161408	0	21	Myocardial infarction	Disease	D009203
18161408	51	69	clomiphene citrate	Chemical	D002996
18161408	122	140	Clomiphene citrate	Chemical	D002996
18161408	142	144	CC	Chemical	D002996
18161408	244	259	Thromboembolism	Disease	D013923
18161408	358	360	CC	Chemical	D002996
18161408	374	393	coronary thrombosis	Disease	D003328
18161408	397	412	thromboembolism	Disease	D013923
18161408	495	516	myocardial infarction	Disease	D009203
18161408	518	520	MI	Disease	D009203
18161408	659	661	CC	Chemical	D002996
18161408	705	715	chest pain	Disease	D002637
18161408	773	794	myocardial infarction	Disease	D009203
18161408	962	978	radiation injury	Disease	D011832
18161408	1192	1194	CC	Chemical	D002996
18161408	1199	1220	myocardial infarction	Disease	D009203
18161408	1222	1232	Thrombosis	Disease	D013927
18161408	1279	1281	CC	Chemical	D002996
18161408	CID	D002996	D009203
18161408	CID	D002996	D013923

17574447|t|Hepatonecrosis and cholangitis related to long-term phenobarbital therapy: an autopsy report of two patients.
17574447|a|Phenobarbital (PB) has a reputation for safety, and it is commonly believed that PB-related increases in serum aminotransferase levels do not indicate or predict the development of significant chronic liver disease. Here we report of two adult patients with a long history of epilepsy treated with PB who died suddenly: one as consequence of cardiac arrest, the other of acute bronchopneumonia. At autopsy, analysis of liver parenchyma revealed rich portal inflammatory infiltrate, which consisted of mixed eosinophil and monocyte cells, associated with several foci of necrosis surrounded by a hard ring of non-specific granulomatous tissue. Inflammatory reactions of internal and external hepatic biliary ducts were also seen. Our findings illustrate that PB may be associated with chronic liver damage, which may lead to more serious and deleterious consequences. For this reason, each clinician should recognize this entity in the differential diagnosis of PB-related asymptomatic chronic hepatic enzyme dysfunction.
17574447	0	14	Hepatonecrosis	Disease	-1
17574447	19	30	cholangitis	Disease	D002761
17574447	52	65	phenobarbital	Chemical	D010634
17574447	110	123	Phenobarbital	Chemical	D010634
17574447	125	127	PB	Chemical	D010634
17574447	191	193	PB	Chemical	D010634
17574447	311	324	liver disease	Disease	D008107
17574447	386	394	epilepsy	Disease	D004827
17574447	408	410	PB	Chemical	D010634
17574447	452	466	cardiac arrest	Disease	D006323
17574447	487	503	bronchopneumonia	Disease	D001996
17574447	680	688	necrosis	Disease	D009336
17574447	868	870	PB	Chemical	D010634
17574447	902	914	liver damage	Disease	D008107
17574447	1071	1073	PB	Chemical	D010634
17574447	1095	1129	chronic hepatic enzyme dysfunction	Disease	D056487
17574447	CID	D010634	D002761
17574447	CID	D010634	D008107

16710500|t|Ethambutol-associated optic neuropathy.
16710500|a|INTRODUCTION: Ethambutol is used in the treatment of tuberculosis, which is still prevalent in Southeast Asia, and can be associated with permanent visual loss. We report 3 cases which presented with bitemporal hemianopia. CLINICAL PICTURE: Three patients with ethambutol-associated toxic optic neuropathy are described. All 3 patients had loss of central visual acuity, colour vision (Ishihara) and visual field. The visual field loss had a bitemporal flavour, suggesting involvement of the optic chiasm. TREATMENT: Despite stopping ethambutol on diagnosis, visual function continued to deteriorate for a few months. Subsequent improvement was mild in 2 cases. In the third case, visual acuity and colour vision normalised but the optic discs were pale. OUTCOME: All 3 patients had some permanent loss of visual function. CONCLUSIONS: Ethambutol usage is associated with permanent visual loss and should be avoided if possible or used with caution and proper ophthalmological follow-up. The author postulates that in cases of ethambutol associated chiasmopathy, ethambutol may initially affect the optic nerves and subsequently progress to involve the optic chiasm.
16710500	0	10	Ethambutol	Chemical	D004977
16710500	22	38	optic neuropathy	Disease	D009901
16710500	54	64	Ethambutol	Chemical	D004977
16710500	93	105	tuberculosis	Disease	D014376
16710500	188	199	visual loss	Disease	D014786
16710500	240	261	bitemporal hemianopia	Disease	D006423
16710500	301	311	ethambutol	Chemical	D004977
16710500	329	345	optic neuropathy	Disease	D009901
16710500	380	452	loss of central visual acuity, colour vision (Ishihara) and visual field	Disease	D014786
16710500	458	475	visual field loss	Disease	D014786
16710500	574	584	ethambutol	Chemical	D004977
16710500	838	861	loss of visual function	Disease	D014786
16710500	876	886	Ethambutol	Chemical	D004977
16710500	922	933	visual loss	Disease	D014786
16710500	1067	1077	ethambutol	Chemical	D004977
16710500	1103	1113	ethambutol	Chemical	D004977
16710500	CID	D004977	D009901
16710500	CID	D004977	D014786

11694026|t|Tolerability of nimesulide and paracetamol in patients with NSAID-induced urticaria/angioedema.
11694026|a|Previous studies evaluated the tolerance of nimesulide and paracetamol in subjects with cutaneous, respiratory and anaphylactoid reactions induced by nonsteroidal anti-inflammatory drugs (NSAIDs). In this study we investigated tolerability and reliability of nimesulide and paracetamol in a very large number of patients with an exclusive well-documented history of NSAID-induced urticaria/angioedema. Furthermore, we evaluated whether some factors have the potential to increase the risk of reaction to paracetamol and nimesulide. A single-placebo-controlled oral challenge procedure with nimesulide or paracetamol was applied to 829 patients with a history of NSAID-induced urticaria/angioedema. A total of 75/829 (9.4%) patients experienced reactions to nimesulide or paracetamol. Of the 715 patients tested with nimesulide 62 (8.6%) showed a positive test, while of 114 subjects submitted to the challenge with paracetamol, 13 (9.6%) did not tolerate this drug. Furthermore, 18.28% of patients with a history of chronic urticaria and 11.8% of subjects with an history of NSAID-induced urticaria/angioedema or angioedema alone (with or without chronic urticaria) resulted to be intolerant to alternative drugs. Taken together, our results confirm the good tolerability of nimesulide and paracetamol in patients who experienced urticaria/angioedema caused by NSAIDs. However, the risk of reaction to these alternative study drugs is statistically increased by a history of chronic urticaria and, above all, by a history of NSAID-induced angioedema.
11694026	16	26	nimesulide	Chemical	C012655
11694026	31	42	paracetamol	Chemical	D000082
11694026	60	65	NSAID	Chemical	D000894
11694026	74	83	urticaria	Disease	D014581
11694026	84	94	angioedema	Disease	D000799
11694026	140	150	nimesulide	Chemical	C012655
11694026	155	166	paracetamol	Chemical	D000082
11694026	246	282	nonsteroidal anti-inflammatory drugs	Chemical	D000894
11694026	284	290	NSAIDs	Chemical	D000894
11694026	355	365	nimesulide	Chemical	C012655
11694026	370	381	paracetamol	Chemical	D000082
11694026	462	467	NSAID	Chemical	D000894
11694026	476	485	urticaria	Disease	D014581
11694026	486	496	angioedema	Disease	D000799
11694026	600	611	paracetamol	Chemical	D000082
11694026	616	626	nimesulide	Chemical	C012655
11694026	686	696	nimesulide	Chemical	C012655
11694026	700	711	paracetamol	Chemical	D000082
11694026	758	763	NSAID	Chemical	D000894
11694026	772	781	urticaria	Disease	D014581
11694026	782	792	angioedema	Disease	D000799
11694026	853	863	nimesulide	Chemical	C012655
11694026	867	878	paracetamol	Chemical	D000082
11694026	912	922	nimesulide	Chemical	C012655
11694026	1011	1022	paracetamol	Chemical	D000082
11694026	1120	1129	urticaria	Disease	D014581
11694026	1171	1176	NSAID	Chemical	D000894
11694026	1185	1194	urticaria	Disease	D014581
11694026	1195	1205	angioedema	Disease	D000799
11694026	1209	1219	angioedema	Disease	D000799
11694026	1251	1260	urticaria	Disease	D014581
11694026	1371	1381	nimesulide	Chemical	C012655
11694026	1386	1397	paracetamol	Chemical	D000082
11694026	1426	1435	urticaria	Disease	D014581
11694026	1436	1446	angioedema	Disease	D000799
11694026	1457	1463	NSAIDs	Chemical	D000894
11694026	1579	1588	urticaria	Disease	D014581
11694026	1621	1626	NSAID	Chemical	D000894
11694026	1635	1645	angioedema	Disease	D000799
11694026	CID	C012655	D000799
11694026	CID	D000082	D000799
11694026	CID	D000894	D000799

11282081|t|Effects of verapamil on atrial fibrillation and its electrophysiological determinants in dogs.
11282081|a|BACKGROUND: Atrial tachycardia-induced remodeling promotes the occurrence and maintenance of atrial fibrillation (AF) and decreases L-type Ca(2+) current. There is also a clinical suggestion that acute L-type Ca(2) channel blockade can promote AF, consistent with an AF promoting effect of Ca(2+) channel inhibition. METHODS: To evaluate the potential mechanisms of AF promotion by Ca(2+) channel blockers, we administered verapamil to morphine-chloralose anesthetized dogs. Diltiazem was used as a comparison drug and autonomic blockade with atropine and nadolol was applied in some experiments. Epicardial mapping with 240 epicardial electrodes was used to evaluate activation during AF. RESULTS: Verapamil caused AF promotion in six dogs, increasing mean duration of AF induced by burst pacing, from 8+/-4 s (mean+/-S.E.) to 95+/-39 s (P<0.01 vs. control) at a loading dose of 0.1 mg/kg and 228+/-101 s (P<0.0005 vs. control) at a dose of 0.2 mg/kg. Underlying electrophysiological mechanisms were studied in detail in five additional dogs under control conditions and in the presence of the higher dose of verapamil. In these experiments, verapamil shortened mean effective refractory period (ERP) from 122+/-5 to 114+/-4 ms (P<0.02) at a cycle length of 300 ms, decreased ERP heterogeneity (from 15+/-1 to 10+/-1%, P<0.05), heterogeneously accelerated atrial conduction and decreased the cycle length of AF (94+/-4 to 84+/-3 ms, P<0.005). Diltiazem did not affect ERP, AF cycle length or AF duration, but produced conduction acceleration similar to that caused by verapamil (n=5). In the presence of autonomic blockade, verapamil failed to promote AF and increased, rather than decreasing, refractoriness. Neither verapamil nor diltiazem affected atrial conduction in the presence of autonomic blockade. Epicardial mapping suggested that verapamil promoted AF by increasing the number of simultaneous wavefronts reflected by separate zones of reactivation in each cycle. CONCLUSIONS: Verapamil promotes AF in normal dogs by promoting multiple circuit reentry, an effect dependent on intact autonomic tone and not shared by diltiazem.
11282081	11	20	verapamil	Chemical	D014700
11282081	24	43	atrial fibrillation	Disease	D001281
11282081	107	125	Atrial tachycardia	Disease	D013617
11282081	188	207	atrial fibrillation	Disease	D001281
11282081	209	211	AF	Disease	D001281
11282081	234	236	Ca	Chemical	D002118
11282081	304	306	Ca	Chemical	D002118
11282081	339	341	AF	Disease	D001281
11282081	362	364	AF	Disease	D001281
11282081	385	387	Ca	Chemical	D002118
11282081	461	463	AF	Disease	D001281
11282081	477	479	Ca	Chemical	D002118
11282081	518	527	verapamil	Chemical	D014700
11282081	531	539	morphine	Chemical	D009020
11282081	540	550	chloralose	Chemical	D002698
11282081	570	579	Diltiazem	Chemical	D004110
11282081	638	646	atropine	Chemical	D001285
11282081	651	658	nadolol	Chemical	D009248
11282081	781	783	AF	Disease	D001281
11282081	794	803	Verapamil	Chemical	D014700
11282081	811	813	AF	Disease	D001281
11282081	865	867	AF	Disease	D001281
11282081	1205	1214	verapamil	Chemical	D014700
11282081	1238	1247	verapamil	Chemical	D014700
11282081	1504	1506	AF	Disease	D001281
11282081	1539	1548	Diltiazem	Chemical	D004110
11282081	1569	1571	AF	Disease	D001281
11282081	1588	1590	AF	Disease	D001281
11282081	1664	1673	verapamil	Chemical	D014700
11282081	1720	1729	verapamil	Chemical	D014700
11282081	1748	1750	AF	Disease	D001281
11282081	1814	1823	verapamil	Chemical	D014700
11282081	1828	1837	diltiazem	Chemical	D004110
11282081	1938	1947	verapamil	Chemical	D014700
11282081	1957	1959	AF	Disease	D001281
11282081	2084	2093	Verapamil	Chemical	D014700
11282081	2103	2105	AF	Disease	D001281
11282081	2223	2232	diltiazem	Chemical	D004110
11282081	CID	D014700	D001281

10074612|t|Hypotension, bradycardia, and asystole after high-dose intravenous methylprednisolone in a monitored patient.
10074612|a|We report a case of hypotension, bradycardia, and asystole after intravenous administration of high-dose methylprednisolone in a 73-year-old patient who underwent electrocardiographic (ECG) monitoring throughout the episode. There was a history of ischemic cardiac disease 9 years earlier. The patient was admitted with a pulmonary-renal syndrome with hemoptysis, rapidly progressive renal failure, and hypoxemia that required mechanical ventilation in the intensive care unit. After receiving advanced cardiopulmonary resuscitation, the patient recovered cardiac rhythm. The ECG showed a junctional rhythm without ventricular arrhythmia. This study reviews the current proposed mechanisms of sudden death after a high dose of intravenous methylprednisolone (IVMP). These mechanisms are not well understood because, in most cases, the patients were not monitored at the moment of the event. Rapid infusion and underlying cardiac disease were important risk factors in the case reported here, and the authors discount ventricular arrhythmia as the main mechanism.
10074612	0	11	Hypotension	Disease	D007022
10074612	13	24	bradycardia	Disease	D001919
10074612	30	38	asystole	Disease	D006323
10074612	67	85	methylprednisolone	Chemical	D008775
10074612	130	141	hypotension	Disease	D007022
10074612	143	154	bradycardia	Disease	D001919
10074612	160	168	asystole	Disease	D006323
10074612	215	233	methylprednisolone	Chemical	D008775
10074612	358	366	ischemic	Disease	D007511
10074612	367	382	cardiac disease	Disease	D006331
10074612	432	456	pulmonary-renal syndrome	Disease	C538458
10074612	462	472	hemoptysis	Disease	D006469
10074612	494	507	renal failure	Disease	D051437
10074612	513	522	hypoxemia	Disease	D000860
10074612	725	747	ventricular arrhythmia	Disease	D001145
10074612	803	815	sudden death	Disease	D003645
10074612	849	867	methylprednisolone	Chemical	D008775
10074612	869	873	IVMP	Chemical	D008775
10074612	1031	1046	cardiac disease	Disease	D006331
10074612	1127	1149	ventricular arrhythmia	Disease	D001145
10074612	CID	D008775	D001919
10074612	CID	D008775	D006323
10074612	CID	D008775	D007022

9209318|t|Lifetime treatment of mice with azidothymidine (AZT) produces myelodysplasia.
9209318|a|AZT has induced a macrocytic anemia in AIDS patients on long term AZT therapy. It is generally assumed that DNA elongation is stopped by the insertion of AZT into the chain in place of thymidine thus preventing the phosphate hydroxyl linkages and therefore suppresses hemopoietic progenitor cell proliferation in an early stage of differentiation. CBA/Ca male mice started on AZT 0.75 mg/ml H2O at 84 days of age and kept on it for 687 days when dosage reduced to 0.5 mg/ml H2O for a group, another group removed from AZT to see recovery, and third group remained on 0.75 mg. At 687 days mice that had been on 0.75 mg had average platelet counts of 2.5 x 10(6). Histological examination on 9 of 10 mice with such thrombocytopenia showed changes compatible with myelodysplastic syndrome (MDS). A variety of histological patterns was observed. There were two cases of hypocellular myelodysplasia, two cases of hypersegmented myelodysplastic granulocytosis, two cases of hypercellular marrow with abnormal megakaryocytes with bizarre nuclei, one case of megakaryocytic myelosis associated with a hyperplastic marrow, dysmyelopoiesis and a hypocellular marrow and two cases of myelodysplasia with dyserythropoiesis, hemosiderosis and a hypocellular marrow. Above mentioned AZT incorporation may have induced an ineffective hemopoiesis in the primitive hemopoietic progenitor cells, which is known to be seen commonly in the myelodysplastic syndrome.
9209318	32	46	azidothymidine	Chemical	D015215
9209318	48	51	AZT	Chemical	D015215
9209318	62	76	myelodysplasia	Disease	D009190
9209318	78	81	AZT	Chemical	D015215
9209318	96	113	macrocytic anemia	Disease	D000748
9209318	117	121	AIDS	Disease	D000163
9209318	144	147	AZT	Chemical	D015215
9209318	232	235	AZT	Chemical	D015215
9209318	263	272	thymidine	Chemical	D013936
9209318	293	302	phosphate	Chemical	D010710
9209318	454	457	AZT	Chemical	D015215
9209318	596	599	AZT	Chemical	D015215
9209318	791	807	thrombocytopenia	Disease	D013921
9209318	839	863	myelodysplastic syndrome	Disease	D009190
9209318	865	868	MDS	Disease	D009190
9209318	957	971	myelodysplasia	Disease	D009190
9209318	1001	1016	myelodysplastic	Disease	D009190
9209318	1171	1190	hyperplastic marrow	Disease	D001855
9209318	1192	1207	dysmyelopoiesis	Disease	D009190
9209318	1214	1233	hypocellular marrow	Disease	D001855
9209318	1251	1265	myelodysplasia	Disease	D009190
9209318	1271	1288	dyserythropoiesis	Disease	-1
9209318	1290	1303	hemosiderosis	Disease	D006486
9209318	1310	1329	hypocellular marrow	Disease	D001855
9209318	1347	1350	AZT	Chemical	D015215
9209318	1498	1522	myelodysplastic syndrome	Disease	D009190
9209318	CID	D015215	D013921
9209318	CID	D015215	D000748
9209318	CID	D015215	D009190

8742498|t|Influence of diet free of NAD-precursors on acetaminophen hepatotoxicity in mice.
8742498|a|Recently, we demonstrated the hepatoprotective effects of nicotinic acid amide, a selective inhibitor of poly(ADP-ribose) polymerase (PARP; EC 2.4.2.30) on mice suffering from acetaminophen (AAP)-hepatitis, suggesting that the AAP-induced liver injury involves a step which depends on adenoribosylation. The present study investigates the effects of a diet free of precursors of NAD, the substrate on which PARP acts, in female NMRI mice with AAP hepatitis and evaluates the influence of simultaneous ethanol consumption in these animals. Liver injuries were quantified as serum activities of glutamate-oxaloacetate transaminase (GOT) and glutamate-pyruvate transaminase (GPT). While AAP caused a 117-fold elevation of serum transaminase activities in mice kept on a standard laboratory diet, which was significantly exacerbated by ethanol and inhibited by nicotinic acid amide (NAA), adverse effects were noted in animals fed a diet free of precursors of NAD. In these animals, only minor increases of serum transaminase activities were measured in the presence of AAP, and unlike the exacerbation caused by ethanol in mice on a standard diet, the liver damage was inhibited by 50% by ethanol. A further 64% reduction of hepatitis was observed, when NAA was given to ethanol/AAP-mice. Our results provide evidence that the AAP-induced hepatitis and its exacerbation by ethanol can either be reduced by end-product inhibition of PARP by NAA or by dietary depletion of the enzyme's substrate NAD. We see the main application of NAA as for the combinational use in pharmaceutical preparations of acetaminophen in order to avoid hepatic damage in patients treated with this widely used analgesic.
8742498	26	29	NAD	Chemical	D009243
8742498	44	57	acetaminophen	Chemical	D000082
8742498	58	72	hepatotoxicity	Disease	D056486
8742498	140	160	nicotinic acid amide	Chemical	D009536
8742498	187	203	poly(ADP-ribose)	Chemical	D011064
8742498	258	271	acetaminophen	Chemical	D000082
8742498	273	276	AAP	Chemical	D000082
8742498	278	287	hepatitis	Disease	D056486
8742498	309	312	AAP	Chemical	D000082
8742498	321	333	liver injury	Disease	D056486
8742498	461	464	NAD	Chemical	D009243
8742498	525	528	AAP	Chemical	D000082
8742498	529	538	hepatitis	Disease	D056486
8742498	583	590	ethanol	Chemical	D000431
8742498	621	635	Liver injuries	Disease	D056486
8742498	675	684	glutamate	Chemical	D018698
8742498	685	697	oxaloacetate	Chemical	D062907
8742498	721	730	glutamate	Chemical	D018698
8742498	731	739	pyruvate	Chemical	D019289
8742498	766	769	AAP	Chemical	D000082
8742498	914	921	ethanol	Chemical	D000431
8742498	939	959	nicotinic acid amide	Chemical	D009536
8742498	961	964	NAA	Chemical	D009536
8742498	1038	1041	NAD	Chemical	D009243
8742498	1148	1151	AAP	Chemical	D000082
8742498	1191	1198	ethanol	Chemical	D000431
8742498	1231	1243	liver damage	Disease	D056486
8742498	1268	1275	ethanol	Chemical	D000431
8742498	1304	1313	hepatitis	Disease	D056486
8742498	1333	1336	NAA	Chemical	D009536
8742498	1350	1357	ethanol	Chemical	D000431
8742498	1358	1361	AAP	Chemical	D000082
8742498	1406	1409	AAP	Chemical	D000082
8742498	1418	1427	hepatitis	Disease	D056486
8742498	1452	1459	ethanol	Chemical	D000431
8742498	1519	1522	NAA	Chemical	D009536
8742498	1573	1576	NAD	Chemical	D009243
8742498	1609	1612	NAA	Chemical	D009536
8742498	1676	1689	acetaminophen	Chemical	D000082
8742498	1708	1722	hepatic damage	Disease	D056486
8742498	CID	D000082	D056486
8742498	CID	D000431	D056486

2435991|t|Antiarrhythmic plasma concentrations of cibenzoline on canine ventricular arrhythmias.
2435991|a|Using two-stage coronary ligation-, digitalis-, and adrenaline-induced canine ventricular arrhythmias, antiarrhythmic effects of cibenzoline were examined and the minimum effective plasma concentration for each arrhythmia model was determined. Cibenzoline suppressed all the arrhythmias, and the minimum effective plasma concentrations for arrhythmias induced by 24-h coronary ligation, 48-h coronary ligation, digitalis, and adrenaline were 1.9 +/- 0.9 (by 8 mg/kg i.v.), 1.6 +/- 0.5 (by 8 mg/kg i.v.), 0.6 +/- 0.2 (by 2 mg/kg i.v.), and 3.5 +/- 1.3 (by 5 mg/kg i.v.) micrograms/ml, respectively (mean +/- SDM, n = 6-7). The concentration for adrenaline-induced arrhythmia was significantly higher than those for the other types of arrhythmias. This pharmacological profile is similar to those of mexiletine and tocainide, and all three drugs have central nervous system (CNS) stimulant action. Because cibenzoline had only weak hypotensive and sinus node depressive effects and was found to be orally active when given to coronary ligation arrhythmia dogs, its clinical usefulness is expected.
2435991	40	51	cibenzoline	Chemical	C032151
2435991	62	85	ventricular arrhythmias	Disease	D001145
2435991	123	132	digitalis	Chemical	D004071
2435991	139	149	adrenaline	Chemical	D004837
2435991	165	188	ventricular arrhythmias	Disease	D001145
2435991	216	227	cibenzoline	Chemical	C032151
2435991	298	308	arrhythmia	Disease	D001145
2435991	331	342	Cibenzoline	Chemical	C032151
2435991	362	373	arrhythmias	Disease	D001145
2435991	427	438	arrhythmias	Disease	D001145
2435991	498	507	digitalis	Chemical	D004071
2435991	513	523	adrenaline	Chemical	D004837
2435991	731	741	adrenaline	Chemical	D004837
2435991	750	760	arrhythmia	Disease	D001145
2435991	820	831	arrhythmias	Disease	D001145
2435991	885	895	mexiletine	Chemical	D008801
2435991	900	909	tocainide	Chemical	D016677
2435991	991	1002	cibenzoline	Chemical	C032151
2435991	1017	1028	hypotensive	Disease	D007022
2435991	1044	1054	depressive	Disease	D003866
2435991	1129	1139	arrhythmia	Disease	D001145
2435991	CID	D004837	D001145
2435991	CID	D004071	D001145

950631|t|Immunopathology of penicillamine-induced glomerular disease.
950631|a|Four patients with rheumatoid arthritis developed heavy proteinuria after five to 12 months of treatment with D-penicillamine. Light microscopy of renal biopsy samples showed minimal glomerular capillary wall thickening and mesangial matrix increase, or no departure from normal. Electron microscopy, however, revealed subepithelial electron-dense deposits, fusion of epithelial cell foot processes, and evidence of mesangial cell hyperactivity. Immunofluorescence microscopy demonstrated granular capillary wall deposits of IgG and C3. The findings were similar to those in early membranous glomerulonephritis, differences being observed however in the results of staining for the early-acting complement components C1q and C4. It is tentatively concluded that complement was activated by the classical pathway.
950631	19	32	penicillamine	Chemical	D010396
950631	41	59	glomerular disease	Disease	D007674
950631	80	100	rheumatoid arthritis	Disease	D001172
950631	117	128	proteinuria	Disease	D011507
950631	171	186	D-penicillamine	Chemical	D010396
950631	642	671	membranous glomerulonephritis	Disease	D015433
950631	CID	D010396	D007674
950631	CID	D010396	D011507

663266|t|Ventricular fibrillation from diatrizoate with and without chelating agents.
663266|a|The toxicity of Renografin 76% was compared with that of Hypaque 76% by selective injection of each into the right coronary artery of dogs. Renografin contains the chelating agents sodium citrate and disodium edetate, while Hypaque contains calcium disodium edetate and no sodium citrate. Ventricular fibrillation occurred significantly more often with Renografin, suggesting that chelating agents contribute to toxicity in coronary angiography.
663266	0	24	Ventricular fibrillation	Disease	D014693
663266	30	41	diatrizoate	Chemical	D003973
663266	81	89	toxicity	Disease	D064420
663266	93	107	Renografin 76%	Chemical	C027278
663266	134	145	Hypaque 76%	Chemical	C027278
663266	217	227	Renografin	Chemical	D003974
663266	258	272	sodium citrate	Chemical	C102006
663266	277	293	disodium edetate	Chemical	D004492
663266	301	308	Hypaque	Chemical	D003973
663266	318	342	calcium disodium edetate	Chemical	D004492
663266	350	364	sodium citrate	Chemical	C102006
663266	366	390	Ventricular fibrillation	Disease	D014693
663266	430	440	Renografin	Chemical	D003974
663266	489	497	toxicity	Disease	D064420
663266	CID	C027278	D014693
663266	CID	C102006	D014693
663266	CID	D004492	D014693

19319147|t|Rapid reversal of anticoagulation reduces hemorrhage volume in a mouse model of warfarin-associated intracerebral hemorrhage.
19319147|a|Warfarin-associated intracerebral hemorrhage (W-ICH) is a severe type of stroke. There is no consensus on the optimal treatment for W-ICH. Using a mouse model, we tested whether the rapid reversal of anticoagulation using human prothrombin complex concentrate (PCC) can reduce hemorrhagic blood volume. Male CD-1 mice were treated with warfarin (2 mg/kg over 24 h), resulting in a mean (+/-s.d.) International Normalized Ratio of 3.5+/-0.9. First, we showed that an intravenous administration of human PCC rapidly reversed anticoagulation in mice. Second, a stereotactic injection of collagenase was administered to induce hemorrhage in the right striatum. Forty-five minutes later, the animals were randomly treated with PCC (100 U/kg) or saline i.v. (n=12 per group). Twenty-four hours after hemorrhage induction, hemorrhagic blood volume was quantified using a photometric hemoglobin assay. The mean hemorrhagic blood volume was reduced in PCC-treated animals (6.5+/-3.1 microL) compared with saline controls (15.3+/-11.2 microL, P=0.015). In the saline group, 45% of the mice developed large hematomas (i.e., >15 microL). In contrast, such extensive lesions were never found in the PCC group. We provide experimental data suggesting PCC to be an effective acute treatment for W-ICH in terms of reducing hemorrhagic blood volume. Future studies are needed to assess the therapeutic potential emerging from our finding for human W-ICH.
19319147	42	52	hemorrhage	Disease	D006470
19319147	80	88	warfarin	Chemical	D014859
19319147	100	124	intracerebral hemorrhage	Disease	D002543
19319147	126	134	Warfarin	Chemical	D014859
19319147	146	170	intracerebral hemorrhage	Disease	D002543
19319147	174	177	ICH	Disease	D002543
19319147	199	205	stroke	Disease	D020521
19319147	260	263	ICH	Disease	D002543
19319147	354	385	prothrombin complex concentrate	Chemical	C025667
19319147	387	390	PCC	Chemical	C025667
19319147	462	470	warfarin	Chemical	D014859
19319147	628	631	PCC	Chemical	C025667
19319147	749	759	hemorrhage	Disease	D006470
19319147	848	851	PCC	Chemical	C025667
19319147	920	930	hemorrhage	Disease	D006470
19319147	1069	1072	PCC	Chemical	C025667
19319147	1222	1231	hematomas	Disease	D006406
19319147	1312	1315	PCC	Chemical	C025667
19319147	1363	1366	PCC	Chemical	C025667
19319147	1408	1411	ICH	Disease	D002543
19319147	1559	1562	ICH	Disease	D002543
19319147	CID	D014859	D002543

16634859|t|Impact of alcohol exposure after pregnancy recognition on ultrasonographic fetal growth measures.
16634859|a|BACKGROUND: More than 3 decades after Jones and Smith (1973) reported on the devastation caused by alcohol exposure on fetal development, the rates of heavy drinking during pregnancy remain relatively unchanged. Early identification of fetal alcohol exposure and maternal abstinence led to better infant outcomes. This study examined the utility of biometry for detecting alcohol-related fetal growth impairment. METHODS: We obtained fetal ultrasound measures from routine ultrasound examinations for 167 pregnant hazardous drinkers who were enrolled in a brief alcohol intervention study. The fetal measures for women who quit after learning of their pregnancies were compared with measures for women who continued some drinking throughout the course of their pregnancies. Because intensity of alcohol consumption is associated with poorer fetal outcomes, separate analyses were conducted for the heavy (average of >or=5 drinks per drinking day) alcohol consumers. Fetal measures from the heavy-exposed fetuses were also compared with measures from a nondrinking group that was representative of normal, uncomplicated pregnancies from our clinics. Analyses of covariance were used to determine whether there were differences between groups after controlling for influences of gestational age and drug abuse. RESULTS: Nearly half of the pregnant drinkers abstained after learning of their pregnancies. When women reportedly quit drinking early in their pregnancies, fetal growth measures were not significantly different from a non-alcohol-exposed group, regardless of prior drinking patterns. Any alcohol consumption postpregnancy recognition among the heavy drinkers resulted in reduced cerebellar growth as well as decreased cranial to body growth in comparison with women who either quit drinking or who were nondrinkers. Amphetamine abuse was predictive of larger cranial to body growth ratios. CONCLUSIONS: Alterations in fetal biometric measurements were observed among the heavy drinkers only when they continued drinking after becoming aware of their pregnancies. Although the reliance on self-reported drinking is a limitation in this study, these findings support the benefits of early abstinence and the potential for ultrasound examinations in the detection of fetal alcohol effects.
16634859	10	17	alcohol	Chemical	D000431
16634859	197	204	alcohol	Chemical	D000431
16634859	340	347	alcohol	Chemical	D000431
16634859	470	477	alcohol	Chemical	D000431
16634859	492	509	growth impairment	Disease	D006130
16634859	660	667	alcohol	Chemical	D000431
16634859	893	900	alcohol	Chemical	D000431
16634859	1045	1052	alcohol	Chemical	D000431
16634859	1395	1405	drug abuse	Disease	D019966
16634859	1630	1637	alcohol	Chemical	D000431
16634859	1696	1703	alcohol	Chemical	D000431
16634859	1779	1804	reduced cerebellar growth	Disease	D006130
16634859	1816	1848	decreased cranial to body growth	Disease	D006130
16634859	1924	1935	Amphetamine	Chemical	D000661
16634859	2378	2385	alcohol	Chemical	D000431
16634859	CID	D000431	D006130
16634859	CID	D000661	D006130

16471092|t|Urinary symptoms and quality of life changes in Thai women with overactive bladder after tolterodine treatment.
16471092|a|OBJECTIVES: To study the urinary symptoms and quality of life changes in Thai women with overactive bladder (OAB) after tolterodine treatment. MATERIAL AND METHOD: Thirty women (aged 30-77 years) diagnosed as having OAB at the Gynecology Clinic, King Chulalongkorn Memorial Hospital from January to April 2004 were included in the present study. Tolterodine 2 mg, twice daily was given. After 8 weeks treatment, changes in micturition diary variables and tolerability were determined. Short form 36 (SF36) questionaires (Thai version) were given before and after 8 weeks of treatment. RESULTS: At 8 weeks, all micturition per day decreased from 16. 7 +/- 5. 3 to 6. 7 +/- 2.4 times per day. The number of nocturia episodes decreased from 5.4 +/- 4.2 to 1.1 +/- 1.0 times per night. The most common side effect was dry month in 5 cases (16.7%) with 2 cases reporting a moderate degree and 1 case with severe degree. Only one case (3.3%) withdrew from the present study due to a severe dry mouth. The SF-36 scores changed significantly in the domains of physical functioning, role function emotional, social function and mental heath. CONCLUSION: Tolterodine was well tolerated and its effects improved the quality of life in Thai women with OAB.
16471092	64	82	overactive bladder	Disease	D053201
16471092	89	100	tolterodine	Chemical	C099041
16471092	201	219	overactive bladder	Disease	D053201
16471092	221	224	OAB	Disease	D053201
16471092	232	243	tolterodine	Chemical	C099041
16471092	328	331	OAB	Disease	D053201
16471092	458	469	Tolterodine	Chemical	C099041
16471092	817	825	nocturia	Disease	D053158
16471092	926	935	dry month	Disease	D014987
16471092	1096	1105	dry mouth	Disease	D014987
16471092	1257	1268	Tolterodine	Chemical	C099041
16471092	1352	1355	OAB	Disease	D053201
16471092	CID	C099041	D014987

16174948|t|Absence of acute cerebral vasoconstriction after cocaine-associated subarachnoid hemorrhage.
16174948|a|INTRODUCTION: Cocaine use has been associated with neurovascular complications, including arterial vasoconstriction and vasculitis. However, there are few studies of angiographic effects of cocaine on human cerebral arteries. Information on these effects could be obtained from angiograms of patients with cocaine-associated subarachnoid hemorrhage (SAH) who underwent angiography shortly after cocaine use. METHODS: We screened patients with SAH retrospectively and identified those with positive urine toxicology for cocaine or its metabolites. Quantitative arterial diameter measurements from angiograms of these patients were compared to measurements from control patients with SAH who were matched for factors known to influence arterial diameter. Qualitative comparisons of small artery changes also were made. RESULTS: Thirteen patients with positive cocaine toxicology were compared to 26 controls. There were no significant differences between groups in the mean diameters of the intradural internal carotid, sphenoidal segment of the middle cerebral, precommunicating segment of the anterior cerebral, or basilar arteries (p greater than 0.05 for all comparisons, unpaired t-tests). There also were no significant differences between groups when expressing diameters as the sum of the precommunicating segment of the anterior cerebral + sphenoidal segment of the middle cerebral + supraclinoid internal carotid artery + basilar artery divided by the diameter of the petrous internal carotid artery (p greater than 0.05, unpaired t-tests). Qualitative assessments showed two arterial irregularities in the distal vasculature in each group. CONCLUSION: No quantitative evidence for narrowing of large cerebral arteries or qualitative angiographic evidence for distal narrowing or vasculitis could be found in patients who underwent angiography after aneurysmal SAH associated with cocaine use.
16174948	49	56	cocaine	Chemical	D003042
16174948	68	91	subarachnoid hemorrhage	Disease	D013345
16174948	107	114	Cocaine	Chemical	D003042
16174948	144	171	neurovascular complications	Disease	D013901
16174948	213	223	vasculitis	Disease	D014657
16174948	283	290	cocaine	Chemical	D003042
16174948	399	406	cocaine	Chemical	D003042
16174948	418	441	subarachnoid hemorrhage	Disease	D013345
16174948	443	446	SAH	Disease	D013345
16174948	488	495	cocaine	Chemical	D003042
16174948	536	539	SAH	Disease	D013345
16174948	612	619	cocaine	Chemical	D003042
16174948	775	778	SAH	Disease	D013345
16174948	951	958	cocaine	Chemical	D003042
16174948	1881	1891	vasculitis	Disease	D014657
16174948	1951	1961	aneurysmal	Disease	D017542
16174948	1962	1965	SAH	Disease	D013345
16174948	1982	1989	cocaine	Chemical	D003042
16174948	CID	D003042	D017542
16174948	CID	D003042	D013345

15042318|t|Atrial fibrillation following chemotherapy for stage IIIE diffuse large B-cell gastric lymphoma in a patient with myotonic dystrophy (Steinert's disease).
15042318|a|The authors describe the unusual association between diffuse B-cell gastric lymphoma and myotonic dystrophy, the most common form of adult muscular dystrophy, and sudden atrial fibrillation following one cycle of doxorubicin-based chemotherapy in the same patient. Atrial fibrillation or other cardiac arrhythmias are unusual complications in patients treated with chemotherapy. The cardiac toxicity intrinsically associated with the aggressive chemotherapy employed could function as a triggering factor for the arrhythmia in the predisposed myocardium of this patient.
15042318	0	19	Atrial fibrillation	Disease	D001281
15042318	79	95	gastric lymphoma	Disease	C535648
15042318	114	132	myotonic dystrophy	Disease	D009223
15042318	134	152	Steinert's disease	Disease	D009223
15042318	223	239	gastric lymphoma	Disease	C535648
15042318	244	262	myotonic dystrophy	Disease	D009223
15042318	294	312	muscular dystrophy	Disease	D009136
15042318	325	344	atrial fibrillation	Disease	D001281
15042318	368	379	doxorubicin	Chemical	D004317
15042318	420	439	Atrial fibrillation	Disease	D001281
15042318	449	468	cardiac arrhythmias	Disease	D001145
15042318	538	554	cardiac toxicity	Disease	D066126
15042318	668	678	arrhythmia	Disease	D001145
15042318	CID	D004317	D001281

12448656|t|A phase II study of thalidomide in advanced metastatic renal cell carcinoma.
12448656|a|OBJECTIVES: To evaluate the toxicity and activity of thalidomide in patients with advanced metastatic renal cell cancer and to measure changes of one angiogenic factor, vascular endothelial growth factor (VEGF)165, with therapy. PATIENTS AND METHODS: 29 patients were enrolled on a study of thalidomide using an intra-patient dose escalation schedule. Patients began thalidomide at 400 mg/d and escalated as tolerated to 1200 mg/d by day 54. Fifty-nine per cent of patients had had previous therapy with IL-2 and 52% were performance status 2 or 3. Systemic plasma VEGF165 levels were measured by dual monoclonal ELISA in 8 patients. RESULTS: 24 patients were evaluable for response with one partial response of 11 months duration of a patient with hepatic and pulmonary metastases (4%), one minor response, and 2 patients stable for over 6 months. Somnolence and constipation were prominent toxicities and most patients could not tolerate the 1200 mg/day dose level. Systemic plasma VEGF165 levels did not change with therapy. CONCLUSION: These results are consistent with a low level of activity of thalidomide in renal cell carcinoma. Administration of doses over 800 mg/day was difficult to achieve in this patient population, however lower doses were practical. The dose-response relationship, if any, of thalidomide for renal cell carcinoma is unclear.
12448656	20	31	thalidomide	Chemical	D013792
12448656	55	75	renal cell carcinoma	Disease	D002292
12448656	105	113	toxicity	Disease	D064420
12448656	130	141	thalidomide	Chemical	D013792
12448656	179	196	renal cell cancer	Disease	D002292
12448656	368	379	thalidomide	Chemical	D013792
12448656	444	455	thalidomide	Chemical	D013792
12448656	848	858	metastases	Disease	D009362
12448656	926	936	Somnolence	Disease	D006970
12448656	941	953	constipation	Disease	D003248
12448656	969	979	toxicities	Disease	D064420
12448656	1178	1189	thalidomide	Chemical	D013792
12448656	1193	1213	renal cell carcinoma	Disease	D002292
12448656	1387	1398	thalidomide	Chemical	D013792
12448656	1403	1423	renal cell carcinoma	Disease	D002292
12448656	CID	D013792	D003248
12448656	CID	D013792	D006970

12231232|t|The striatum as a target for anti-rigor effects of an antagonist of mGluR1, but not an agonist of group II metabotropic glutamate receptors.
12231232|a|The aim of the present study was to find out whether the metabotropic receptor 1 (mGluR1) and group II mGluRs, localized in the striatum, are involved in antiparkinsonian-like effects in rats. Haloperidol (1 mg/kg ip) induced parkinsonian-like muscle rigidity, measured as an increased resistance of a rat's hind foot to passive flexion and extension at the ankle joint. (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA; 0.5-15 microg/0.5 microl), a potent and selective mGluR1 antagonist, or (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC; 7.5-15 microg/0.5 microl), a selective group II agonist, was injected bilaterally into the striatum of haloperidol-treated animals. AIDA in doses of 7.5-15 microg/0.5 microl diminished the haloperidol-induced muscle rigidity. In contrast, 2R,4R-APDC injections were ineffective. The present results may suggest that the blockade of striatal mGluR1, but not the stimulation of group II mGluRs, may ameliorate parkinsonian muscle rigidity.
12231232	120	129	glutamate	Chemical	D018698
12231232	334	345	Haloperidol	Chemical	D006220
12231232	367	379	parkinsonian	Disease	D010300
12231232	385	400	muscle rigidity	Disease	D009127
12231232	512	551	(RS)-1-aminoindan-1,5-dicarboxylic acid	Chemical	C095756
12231232	553	557	AIDA	Chemical	C095756
12231232	631	675	(2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate	Chemical	C097299
12231232	677	687	2R,4R-APDC	Chemical	C097299
12231232	792	803	haloperidol	Chemical	D006220
12231232	821	825	AIDA	Chemical	C095756
12231232	878	889	haloperidol	Chemical	D006220
12231232	898	913	muscle rigidity	Disease	D009127
12231232	928	938	2R,4R-APDC	Chemical	C097299
12231232	1097	1109	parkinsonian	Disease	D010300
12231232	1110	1125	muscle rigidity	Disease	D009127
12231232	CID	D006220	D009127

11847945|t|Acute cholestatic hepatitis after exposure to isoflurane.
11847945|a|OBJECTIVE: To report a case of acute cholestatic hepatitis following exposure to the inhalational anesthetic isoflurane. CASE SUMMARY: A 70-year-old healthy woman from Iraq developed acute cholestatic hepatitis 3 weeks following repair of the right rotator cuff under general anesthesia. There was no evidence for viral, autoimmune, or metabolic causes of hepatitis. No other medications were involved except for dipyrone for analgesia. The alanine aminotransferase was elevated to a peak concentration of 1533 U/L and the serum bilirubin reached a peak of 17.0 mg/dL. There was slow improvement over 4 months. Accidental reexposure by the patient to dipyrone was uneventful. DISCUSSION: The clinical and histologic picture of this case resembles halothane hepatitis, which has a significant mortality rate. CONCLUSIONS: Isoflurane, a common anesthetic agent, can cause severe cholestatic hepatitis.
11847945	6	27	cholestatic hepatitis	Disease	D002779|D056486	cholestatic|hepatitis
11847945	46	56	isoflurane	Chemical	D007530
11847945	95	116	cholestatic hepatitis	Disease	D002779|D056486	cholestatic|hepatitis
11847945	167	177	isoflurane	Chemical	D007530
11847945	247	268	cholestatic hepatitis	Disease	D002779|D056486	cholestatic|hepatitis
11847945	414	423	hepatitis	Disease	D056486
11847945	471	479	dipyrone	Chemical	D004177
11847945	484	493	analgesia	Disease	D000699
11847945	499	506	alanine	Chemical	D000409
11847945	587	596	bilirubin	Chemical	D001663
11847945	709	717	dipyrone	Chemical	D004177
11847945	805	824	halothane hepatitis	Disease	C562477
11847945	879	889	Isoflurane	Chemical	D007530
11847945	935	956	cholestatic hepatitis	Disease	D002779|D056486	cholestatic|hepatitis
11847945	CID	D007530	D056486
11847945	CID	D007530	D002779

11284996|t|Calcitonin gene-related peptide levels during nitric oxide-induced headache in patients with chronic tension-type headache.
11284996|a|It has been proposed that nitric oxide (NO) induced headache in primary headaches may be associated with release of calcitonin gene-related peptide (CGRP). In the present study we aimed to investigate plasma levels of CGRP during headache induced by the NO donor glyceryl trinitrate (GTN) in 16 patients with chronic tension-type headache and 16 healthy controls. The subjects were randomly allocated to receive 0.5 microg/kg/min GTN or placebo over 20 min on two headache-free days. Blood samples were collected at baseline, 10, 20 and 60 min after start of infusion. Both patients and controls developed significantly stronger immediate headache on the GTN day than on the placebo day and the headache was significantly more pronounced in patients than in controls. There was no difference between the area under the CGRP curve (AUCCGRP) on GTN vs. placebo day in either patients (P=0.65) or controls (P=0.48). The AUCCGRP recorded on the GTN day did not differ between patients and controls (P=0.36). Both in patients and controls, CGRP levels changed significantly over time, on both the GTN and placebo days (P < 0.05). The present study indicates that NO-induced immediate headache is not associated with release of CGRP.
11284996	46	58	nitric oxide	Chemical	D009569
11284996	67	75	headache	Disease	D006261
11284996	101	122	tension-type headache	Disease	D018781
11284996	150	162	nitric oxide	Chemical	D009569
11284996	164	166	NO	Chemical	D009569
11284996	176	184	headache	Disease	D006261
11284996	188	205	primary headaches	Disease	D051270
11284996	354	362	headache	Disease	D006261
11284996	378	380	NO	Chemical	D009569
11284996	387	406	glyceryl trinitrate	Chemical	D005996
11284996	408	411	GTN	Chemical	D005996
11284996	441	462	tension-type headache	Disease	D018781
11284996	554	557	GTN	Chemical	D005996
11284996	588	596	headache	Disease	D006261
11284996	763	771	headache	Disease	D006261
11284996	779	782	GTN	Chemical	D005996
11284996	819	827	headache	Disease	D006261
11284996	967	970	GTN	Chemical	D005996
11284996	1065	1068	GTN	Chemical	D005996
11284996	1216	1219	GTN	Chemical	D005996
11284996	1282	1284	NO	Chemical	D009569
11284996	1303	1311	headache	Disease	D006261
11284996	CID	D005996	D006261
11284996	CID	D009569	D006261

11078231|t|Myocardial ischemia due to coronary artery spasm during dobutamine stress echocardiography.
11078231|a|Dobutamine stress echocardiography (DSE) is a useful and safe provocation test for myocardial ischemia. Until now, the test has been focused only on the organic lesion in the coronary artery, and positive DSE has indicated the presence of significant fixed coronary artery stenosis. The aim of the present study is to examine whether myocardial ischemia due to coronary spasm is induced by dobutamine. We performed DSE on 51 patients with coronary spastic angina but without significant fixed coronary artery stenosis. All patients had anginal attacks at rest with ST elevation on the electrocardiogram (variant angina). Coronary spasm was induced by intracoronary injection of acetylcholine, and no fixed coronary artery stenosis was documented on angiograms in all patients. DSE was performed with intravenous dobutamine infusion with an incremental doses of 5, 10, 20, 30, and 40 microg/kg/min every 5 minutes. Of the 51 patients, 7 patients showed asynergy with ST elevation. All 7 patients (13.7%) had chest pain during asynergy, and both chest pain and electrocardiographic changes were preceded by asynergy. These findings indicate that dobutamine can provoke coronary spasm in some patients with coronary spastic angina. When DSE is performed to evaluate coronary artery disease, not only fixed coronary stenosis, but also coronary spasm should be considered as a genesis of asynergy.
11078231	0	19	Myocardial ischemia	Disease	D017202
11078231	27	48	coronary artery spasm	Disease	D003329
11078231	56	66	dobutamine	Chemical	D004280
11078231	92	102	Dobutamine	Chemical	D004280
11078231	175	194	myocardial ischemia	Disease	D017202
11078231	349	373	coronary artery stenosis	Disease	D023921
11078231	426	445	myocardial ischemia	Disease	D017202
11078231	453	467	coronary spasm	Disease	D003329
11078231	482	492	dobutamine	Chemical	D004280
11078231	531	554	coronary spastic angina	Disease	D000788
11078231	585	609	coronary artery stenosis	Disease	D023921
11078231	628	635	anginal	Disease	D000787
11078231	696	710	variant angina	Disease	D000788
11078231	770	783	acetylcholine	Chemical	D000109
11078231	798	822	coronary artery stenosis	Disease	D023921
11078231	904	914	dobutamine	Chemical	D004280
11078231	1099	1109	chest pain	Disease	D002637
11078231	1136	1146	chest pain	Disease	D002637
11078231	1236	1246	dobutamine	Chemical	D004280
11078231	1259	1273	coronary spasm	Disease	D003329
11078231	1296	1319	coronary spastic angina	Disease	D000788
11078231	1355	1378	coronary artery disease	Disease	D003324
11078231	1395	1412	coronary stenosis	Disease	D023921
11078231	1423	1437	coronary spasm	Disease	D003329
11078231	CID	D004280	D000788
11078231	CID	D004280	D003329

10523326|t|Nitric oxide synthase expression in the course of lead-induced hypertension.
10523326|a|We recently showed elevated reactive oxygen species (ROS), reduced urinary excretion of NO metabolites (NOx), and increased NO sequestration as nitrotyrosine in various tissues in rats with lead-induced hypertension. This study was designed to discern whether the reduction in urinary NOx in lead-induced hypertension is, in part, due to depressed NO synthase (NOS) expression. Male Sprague-Dawley rats were randomly assigned to a lead-treated group (given lead acetate, 100 ppm, in drinking water and regular rat chow), a group given lead and vitamin E-fortified chow, or a normal control group given either regular food and water or vitamin E-fortified food for 12 weeks. Tail blood pressure, urinary NOx excretion, plasma malondialdehyde (MDA), and endothelial and inducible NOS (eNOS and iNOS) isotypes in the aorta and kidney were measured. The lead-treated group exhibited a rise in blood pressure and plasma MDA concentration, a fall in urinary NOx excretion, and a paradoxical rise in vascular and renal tissue eNOS and iNOS expression. Vitamin E supplementation ameliorated hypertension, lowered plasma MDA concentration, and raised urinary NOx excretion while significantly lowering vascular, but not renal, tissue eNOS and iNOS expression. Vitamin E supplementation had no effect on either blood pressure, plasma MDA, or NOS expression in the control group. The study also revealed significant inhibition of NOS enzymatic activity by lead in cell-free preparations. In conclusion, lead-induced hypertension in this model was associated with a compensatory upregulation of renal and vascular eNOS and iNOS expression. This is, in part, due to ROS-mediated NO inactivation, lead-associated inhibition of NOS activity, and perhaps stimulatory actions of increased shear stress associated with hypertension.
10523326	0	12	Nitric oxide	Chemical	D009569
10523326	50	54	lead	Chemical	D007854
10523326	63	75	hypertension	Disease	D006973
10523326	114	120	oxygen	Chemical	D010100
10523326	165	167	NO	Chemical	D009569
10523326	201	203	NO	Chemical	D009569
10523326	221	234	nitrotyrosine	Chemical	C002744
10523326	267	271	lead	Chemical	D007854
10523326	280	292	hypertension	Disease	D006973
10523326	369	373	lead	Chemical	D007854
10523326	382	394	hypertension	Disease	D006973
10523326	425	427	NO	Chemical	D009569
10523326	508	512	lead	Chemical	D007854
10523326	534	546	lead acetate	Chemical	C008261
10523326	612	616	lead	Chemical	D007854
10523326	621	630	vitamin E	Chemical	D014810
10523326	712	721	vitamin E	Chemical	D014810
10523326	802	817	malondialdehyde	Chemical	D008315
10523326	819	822	MDA	Chemical	D008315
10523326	927	931	lead	Chemical	D007854
10523326	992	995	MDA	Chemical	D008315
10523326	1122	1131	Vitamin E	Chemical	D014810
10523326	1160	1172	hypertension	Disease	D006973
10523326	1189	1192	MDA	Chemical	D008315
10523326	1328	1337	Vitamin E	Chemical	D014810
10523326	1401	1404	MDA	Chemical	D008315
10523326	1522	1526	lead	Chemical	D007854
10523326	1569	1573	lead	Chemical	D007854
10523326	1582	1594	hypertension	Disease	D006973
10523326	1743	1745	NO	Chemical	D009569
10523326	1760	1764	lead	Chemical	D007854
10523326	1878	1890	hypertension	Disease	D006973
10523326	CID	D007854	D006973

9867728|t|Risk for valvular heart disease among users of fenfluramine and dexfenfluramine who underwent echocardiography before use of medication.
9867728|a|BACKGROUND: Because uncontrolled echocardiographic surveys suggested that up to 30% to 38% of users of fenfluramine and dexfenfluramine had valvular disease, these drugs were withdrawn from the market. OBJECTIVE: To determine the risk for new or worsening valvular abnormalities among users of fenfluramine or dexfenfluramine who underwent echocardiography before they began to take these medications. DESIGN: Cohort study. SETTING: Academic primary care practices. PATIENTS: 46 patients who used fenfluramine or dexfenfluramine for 14 days or more and had echocardiograms obtained before therapy. MEASUREMENTS: Follow-up echocardiography. The primary outcome was new or worsening valvulopathy, defined as progression of either aortic or mitral regurgitation by at least one degree of severity and disease that met U.S. Food and Drug Administration criteria (at least mild aortic regurgitation or moderate mitral regurgitation). RESULTS: Two patients (4.3% [95% CI, 0.6% to 14.8%]) receiving fenfluramine-phentermine developed valvular heart disease. One had baseline bicuspid aortic valve and mild aortic regurgitation that progressed to moderate regurgitation. The second patient developed new moderate aortic insufficiency. CONCLUSION: Users of diet medications are at risk for valvular heart disease. However, the incidence may be lower than that reported previously.
9867728	9	31	valvular heart disease	Disease	D006349
9867728	47	59	fenfluramine	Chemical	D005277
9867728	64	79	dexfenfluramine	Chemical	D020372
9867728	240	252	fenfluramine	Chemical	D005277
9867728	257	272	dexfenfluramine	Chemical	D020372
9867728	277	293	valvular disease	Disease	D006349
9867728	393	415	valvular abnormalities	Disease	D006349
9867728	431	443	fenfluramine	Chemical	D005277
9867728	447	462	dexfenfluramine	Chemical	D020372
9867728	634	646	fenfluramine	Chemical	D005277
9867728	650	665	dexfenfluramine	Chemical	D020372
9867728	818	830	valvulopathy	Disease	D006349
9867728	865	895	aortic or mitral regurgitation	Disease	D001022|D008944	aortic regurgitation|mitral regurgitation
9867728	1010	1030	aortic regurgitation	Disease	D001022
9867728	1043	1063	mitral regurgitation	Disease	D008944
9867728	1129	1141	fenfluramine	Chemical	D005277
9867728	1142	1153	phentermine	Chemical	D010645
9867728	1164	1186	valvular heart disease	Disease	D006349
9867728	1205	1226	bicuspid aortic valve	Disease	C562388
9867728	1236	1256	aortic regurgitation	Disease	D001022
9867728	1342	1362	aortic insufficiency	Disease	D001022
9867728	1418	1440	valvular heart disease	Disease	D006349
9867728	CID	D005277	D001022
9867728	CID	D010645	D001022

9636837|t|Carboplatin toxic effects on the peripheral nervous system of the rat.
9636837|a|BACKGROUND: The most striking of carboplatin's advantages (CBDCA) over cisplatin (CDDP) is its markedly reduced rate of neurotoxic effects. However, the use of CBDCA higher-intensity schedules and the association with other neurotoxic drugs in polychemotherapy may cause some concern about its safety with respect to peripheral nervous system damage. MATERIALS AND METHODS: Two different schedules of CBDCA administration (10 mg/kg and 15 mg/kg i.p. twice a week for nine times) were evaluated in Wistar rats. Neurotoxicity was assessed for behavioral (tail-flick test), neurophysiological (nerve conduction velocity in the tail nerve), morphological, morphometrical and analytical effects. RESULTS: CBDCA administration induced dose-dependent peripheral neurotoxicity. Pain perception and nerve conduction velocity in the tail were significantly impaired, particularly after the high-dose treatment. The dorsal root ganglia sensory neurons and, to a lesser extent, satellite cells showed the same changes as those induced by CDDP, mainly affecting the nucleus and nucleolus of ganglionic sensory neurons. Moreover, significant amounts of platinum were detected in the dorsal root ganglia and kidney after CBDCA treatment. CONCLUSIONS: CBDCA is neurotoxic in our model, and the type of pathological changes it induces are so closely similar to those caused by CDDP that it is probable that neurotoxicity is induced in the two drugs by the same mechanism. This model can be used alone or in combination with other drugs to explore the effect of CBDCA on the peripheral nervous system.
9636837	0	11	Carboplatin	Chemical	D016190
9636837	104	115	carboplatin	Chemical	D016190
9636837	130	135	CBDCA	Chemical	D016190
9636837	142	151	cisplatin	Chemical	D002945
9636837	153	157	CDDP	Chemical	D002945
9636837	191	201	neurotoxic	Disease	D020258
9636837	231	236	CBDCA	Chemical	D016190
9636837	295	305	neurotoxic	Disease	D020258
9636837	388	420	peripheral nervous system damage	Disease	D010523
9636837	472	477	CBDCA	Chemical	D016190
9636837	581	594	Neurotoxicity	Disease	D020258
9636837	771	776	CBDCA	Chemical	D016190
9636837	815	839	peripheral neurotoxicity	Disease	D010523
9636837	841	845	Pain	Disease	D010146
9636837	1097	1101	CDDP	Chemical	D002945
9636837	1210	1218	platinum	Chemical	D010984
9636837	1277	1282	CBDCA	Chemical	D016190
9636837	1307	1312	CBDCA	Chemical	D016190
9636837	1316	1326	neurotoxic	Disease	D020258
9636837	1431	1435	CDDP	Chemical	D002945
9636837	1461	1474	neurotoxicity	Disease	D020258
9636837	1615	1620	CBDCA	Chemical	D016190
9636837	CID	D002945	D010523
9636837	CID	D016190	D010523

9579567|t|Iatrogenic risks of endometrial carcinoma after treatment for breast cancer in a large French case-control study. F  d  ration Nationale des Centres de Lutte Contre le Cancer (FNCLCC).
9579567|a|Since tamoxifen is widely used in breast cancer treatment and has been proposed for the prevention of breast cancer, its endometrial iatrogenic effects must be carefully examined. We have investigated the association between endometrial cancer and tamoxifen use or other treatments in women treated for breast cancer in a case-control study. Cases of endometrial cancer diagnosed after breast cancer (n = 135) and 467 controls matched for age, year of diagnosis of breast cancer and hospital and survival time with an intact uterus were included. Women who had received tamoxifen were significantly more likely to have endometrial cancer diagnosed than those who had not (crude relative risk = 4.9, p = 0.0001). Univariate and adjusted analyses showed that the risk increased with the length of treatment (p = 0.0001) or the cumulative dose of tamoxifen received (p = 0.0001), irrespective of the daily dose. Women who had undergone pelvic radiotherapy also had a higher risk (crude relative risk = 7.8, p = 0.0001). After adjusting for confounding factors, the risk was higher for tamoxifen users (p = 0.0012), treatment for more than 3 years (all p < 0.03) and pelvic radiotherapy (p = 0.012). Women who had endometrial cancer and had received tamoxifen had more advanced disease and poorer prognosis than those with endometrial cancer who had not received this treatment. Our results suggest a causal role of tamoxifen in endometrial cancer, particularly when used as currently proposed for breast cancer prevention. Pelvic radiotherapy may be an additional iatrogenic factor for women with breast cancer. Endometrial cancers diagnosed in women treated with tamoxifen have poorer prognosis. Women who receive tamoxifen for breast cancer should be offered gynaecological surveillance during and after treatment. A long-term evaluation of the risk-benefit ratio of tamoxifen as a preventive treatment for breast cancer is clearly warranted.
9579567	20	41	endometrial carcinoma	Disease	D016889
9579567	62	75	breast cancer	Disease	D001943
9579567	191	200	tamoxifen	Chemical	D013629
9579567	219	232	breast cancer	Disease	D001943
9579567	287	300	breast cancer	Disease	D001943
9579567	410	428	endometrial cancer	Disease	D016889
9579567	433	442	tamoxifen	Chemical	D013629
9579567	488	501	breast cancer	Disease	D001943
9579567	536	554	endometrial cancer	Disease	D016889
9579567	571	584	breast cancer	Disease	D001943
9579567	650	663	breast cancer	Disease	D001943
9579567	755	764	tamoxifen	Chemical	D013629
9579567	804	822	endometrial cancer	Disease	D016889
9579567	1029	1038	tamoxifen	Chemical	D013629
9579567	1267	1276	tamoxifen	Chemical	D013629
9579567	1395	1413	endometrial cancer	Disease	D016889
9579567	1431	1440	tamoxifen	Chemical	D013629
9579567	1450	1466	advanced disease	Disease	D020178
9579567	1504	1522	endometrial cancer	Disease	D016889
9579567	1597	1606	tamoxifen	Chemical	D013629
9579567	1610	1628	endometrial cancer	Disease	D016889
9579567	1679	1692	breast cancer	Disease	D001943
9579567	1779	1792	breast cancer	Disease	D001943
9579567	1794	1813	Endometrial cancers	Disease	D016889
9579567	1846	1855	tamoxifen	Chemical	D013629
9579567	1897	1906	tamoxifen	Chemical	D013629
9579567	1911	1924	breast cancer	Disease	D001943
9579567	2051	2060	tamoxifen	Chemical	D013629
9579567	2091	2104	breast cancer	Disease	D001943
9579567	CID	D013629	D016889

9205462|t|Granulosa cell tumor of the ovary associated with antecedent tamoxifen use.
9205462|a|BACKGROUND: Increased attention has been focused recently on the estrogenic effects of tamoxifen. Review of the literature reveals an association between tamoxifen use and gynecologic tumors. CASE: A 52-year-old postmenopausal woman was treated with tamoxifen for stage II estrogen receptor-positive breast carcinoma. Her aspartate transaminase and alanine transaminase levels increase markedly after 6 months of tamoxifen use. After an additional 17 months of elevated serum transaminases, the patient was found to have a stage Ic granulosa cell tumor of the ovary. CONCLUSION: Patients with tamoxifen-induced liver dysfunction may be at increased risk for granulosa cell tumors because of alterations in tamoxifen metabolism.
9205462	0	33	Granulosa cell tumor of the ovary	Disease	C537296
9205462	61	70	tamoxifen	Chemical	D013629
9205462	163	172	tamoxifen	Chemical	D013629
9205462	230	239	tamoxifen	Chemical	D013629
9205462	260	266	tumors	Disease	D009369
9205462	326	335	tamoxifen	Chemical	D013629
9205462	349	357	estrogen	Chemical	D004967
9205462	376	392	breast carcinoma	Disease	D001943
9205462	398	407	aspartate	Chemical	D001224
9205462	425	432	alanine	Chemical	D000409
9205462	489	498	tamoxifen	Chemical	D013629
9205462	608	641	granulosa cell tumor of the ovary	Disease	C537296
9205462	669	678	tamoxifen	Chemical	D013629
9205462	687	704	liver dysfunction	Disease	D017093
9205462	734	755	granulosa cell tumors	Disease	D006106
9205462	782	791	tamoxifen	Chemical	D013629
9205462	CID	D013629	D017093
9205462	CID	D013629	C537296

9098464|t|A murine model of adenomyosis: the effects of hyperprolactinemia induced by fluoxetine hydrochloride, a selective serotonin reuptake inhibitor, on adenomyosis induction in Wistar albino rats.
9098464|a|OBJECTIVE: The aim of this study was to investigate whether fluoxetine given to castrated and noncastrated rats caused hyperprolactinemia and its effects with respect to adenomyosis. DESIGN: Fluoxetine, a serotonin reuptake inhibitor, was given to Wistar Albino rats for 98 days to produce hyperprolactinemia. The drug was given to two groups consisting of castrated and noncastrated rats and compared to two groups of castrated and noncastrated controls. Prolactin levels were measured and the uteri of the rats were removed for histopathological analysis at the end of 98 days. SETTING: Marmara University School of Medicine, Department of Histology and Embryology, Zeynep Kamil Women and Children's Hospital. MAIN OUTCOME MEASURES: Serum prolactin levels, uterine histopathology. RESULTS: The prolactin levels of castrated and noncastrated groups treated with fluoxetine were statistically significantly higher when compared to their respective control groups. Histological studies revealed 11 cases of adenomyosis, all within the noncastrated group receiving fluoxetine. CONCLUSION: It was suggested that high serum prolactin levels cause degeneration of myometrial cells in the presence of ovarian steroids that results in a myometrial invasion by endometrial stroma. This invasion eventually progresses to adenomyosis.
9098464	18	29	adenomyosis	Disease	D062788
9098464	46	64	hyperprolactinemia	Disease	D006966
9098464	76	100	fluoxetine hydrochloride	Chemical	D005473
9098464	114	123	serotonin	Chemical	D012701
9098464	147	158	adenomyosis	Disease	D062788
9098464	252	262	fluoxetine	Chemical	D005473
9098464	311	329	hyperprolactinemia	Disease	D006966
9098464	362	373	adenomyosis	Disease	D062788
9098464	383	393	Fluoxetine	Chemical	D005473
9098464	397	406	serotonin	Chemical	D012701
9098464	482	500	hyperprolactinemia	Disease	D006966
9098464	1055	1065	fluoxetine	Chemical	D005473
9098464	1198	1209	adenomyosis	Disease	D062788
9098464	1255	1265	fluoxetine	Chemical	D005473
9098464	1395	1403	steroids	Chemical	D013256
9098464	1504	1515	adenomyosis	Disease	D062788
9098464	CID	D005473	D006966
9098464	CID	D005473	D062788

8424298|t|Effects of deliberate hypotension induced by labetalol with isoflurane on neuropsychological function.
8424298|a|The effect of deliberate hypotension on brain function measured by neuropsychological tests was studied in 41 adult patients. Twenty-four patients were anaesthetized for middle-ear surgery with deliberate hypotension induced by labetalol with isoflurane (hypotensive group). Seventeen patients without hypotension served as a control group. The mean arterial pressure was 77 +/- 2 mmHg (10.3 +/- 0.3 kPa) before hypotension and 50 +/- 0 mmHg (6.7 +/- 0.0 kPa) during hypotension in the hypotensive group, and 86 +/- 2 mmHg (11.5 +/- 0.3 kPa) during anaesthesia in the control group. The following psychological tests were performed: four subtests of the Wechsler Adult Intelligence Scale (similarities, digit span, vocabulary and digit symbol), Trail-Making tests A and B, Zung tests (self-rating anxiety scale and self-rating depression scale) and two-part memory test battery with immediate and delayed recall. The tests were performed preoperatively and 2 days postoperatively. There were no statistically significant differences between the groups in any of the tests in the changes from preoperative value to postoperative value. The results indicate that hypotension induced by labetalol with isoflurane has no significant harmful effects on mental functions compared to normotensive anaesthesia.
8424298	22	33	hypotension	Disease	D007022
8424298	45	54	labetalol	Chemical	D007741
8424298	60	70	isoflurane	Chemical	D007530
8424298	128	139	hypotension	Disease	D007022
8424298	308	319	hypotension	Disease	D007022
8424298	331	340	labetalol	Chemical	D007741
8424298	346	356	isoflurane	Chemical	D007530
8424298	358	369	hypotensive	Disease	D007022
8424298	405	416	hypotension	Disease	D007022
8424298	515	526	hypotension	Disease	D007022
8424298	570	581	hypotension	Disease	D007022
8424298	589	600	hypotensive	Disease	D007022
8424298	900	907	anxiety	Disease	D001008
8424298	930	940	depression	Disease	D003866
8424298	1264	1275	hypotension	Disease	D007022
8424298	1287	1296	labetalol	Chemical	D007741
8424298	1302	1312	isoflurane	Chemical	D007530
8424298	CID	D007741	D007022
8424298	CID	D007530	D007022

7880714|t|Auditory disturbance associated with interscalene brachial plexus block.
7880714|a|We performed an audiometric study in 20 patients who underwent surgery of the shoulder region under an interscalene brachial plexus block (IBPB). Bupivacaine 0.75% with adrenaline was given followed by a 24-hr continuous infusion of 0.25% bupivacaine. Three audiometric threshold measurements (0.25-18 kHz) were made: the first before IBPB, the second 2-6 h after surgery and the third on the first day after operation. In four patients hearing impairment on the side of the block was demonstrated after operation, in three measurements on the day of surgery and in one on the following day. The frequencies at which the impairment occurred varied between patients; in one only low frequencies (0.25-0.5 kHz) were involved. The maximum change in threshold was 35 dB at 6 kHz measured at the end of the continuous infusion of bupivacaine. This patient had hearing threshold changes (15-20 dB) at 6-10 kHz on the opposite side also. IBPB may cause transient auditory dysfunction in the ipsilateral ear, possibly via an effect on sympathetic innervation.
7880714	219	230	Bupivacaine	Chemical	D002045
7880714	242	252	adrenaline	Chemical	D004837
7880714	312	323	bupivacaine	Chemical	D002045
7880714	510	528	hearing impairment	Disease	D034381
7880714	898	909	bupivacaine	Chemical	D002045
7880714	1029	1049	auditory dysfunction	Disease	D006311
7880714	CID	D002045	D034381
7880714	CID	D004837	D034381

7102237|t|Midazolam compared with thiopentone as an induction agent.
7102237|a|In patients premedicated with scopolamine + morphine (+5 mg nitrazepam the evening before surgery), the sleep-inducing effect of midazolam 0.15 mg/kg i.v. was clearly slower in onset than that of thiopentone 4.67 mg/kg i.v. Somewhat fewer cardiovascular and local sequelae were found in the midazolam group, but, although apnoea occurred less often in the midazolam group it lasted longer. On the whole, the differences between midazolam and thiopentone had no apparent clinical consequences. Midazolam is a new alternative agent for induction in combination anaesthesia.
7102237	0	9	Midazolam	Chemical	D008874
7102237	24	35	thiopentone	Chemical	D013874
7102237	89	100	scopolamine	Chemical	D012601
7102237	103	111	morphine	Chemical	D009020
7102237	119	129	nitrazepam	Chemical	D009567
7102237	188	197	midazolam	Chemical	D008874
7102237	255	266	thiopentone	Chemical	D013874
7102237	350	359	midazolam	Chemical	D008874
7102237	381	387	apnoea	Disease	D001049
7102237	415	424	midazolam	Chemical	D008874
7102237	487	496	midazolam	Chemical	D008874
7102237	501	512	thiopentone	Chemical	D013874
7102237	552	561	Midazolam	Chemical	D008874
7102237	CID	D008874	D001049
7102237	CID	D013874	D001049

6769133|t|Cardiotoxic and possible leukemogenic effects of adriamycin in nonhuman primates.
6769133|a|10 monkeys (macaques) received adriamycin by monthly intravenous injections at 12 mg/m2 (1 mg/kg). 8 of the 10 monkeys developed congestive heart failure at an average cumulative adriamycin dose (310 mg/m2) well below that considered the safe upper limit (550 mg/m2) in man. Histologically, the myocardial lesions resembled those found in human anthracycline-induced cardiomyopathy. 1 of the 10 monkeys developed acute myeloblastic leukemia after receiving 324 mg/m2 of adriamycin; the 10th monkey is alive and well 26 months after the last dose of drug. Our results suggest that adriamycin is a more potent cardiotoxin in monkeys than in man, and that leukemia may be a consequence of prolonged treatment with this drug.
6769133	0	11	Cardiotoxic	Disease	D066126
6769133	49	59	adriamycin	Chemical	D004317
6769133	113	123	adriamycin	Chemical	D004317
6769133	211	235	congestive heart failure	Disease	D006333
6769133	261	271	adriamycin	Chemical	D004317
6769133	377	395	myocardial lesions	Disease	D001768
6769133	427	440	anthracycline	Chemical	D018943
6769133	449	463	cardiomyopathy	Disease	D009202
6769133	495	522	acute myeloblastic leukemia	Disease	D015470
6769133	552	562	adriamycin	Chemical	D004317
6769133	662	672	adriamycin	Chemical	D004317
6769133	735	743	leukemia	Disease	D007938
6769133	CID	D004317	D006333
6769133	CID	D004317	D015470

6292680|t|Doxorubicin cardiomyopathy in children with left-sided Wilms tumor.
6292680|a|Two children with Wilms tumor of the left kidney experienced severe anthracycline cardiomyopathy after irradiation to the tumor bed and conventional dosage of doxorubicin. The cardiomyopathy is attributed 1) to the fact that radiation fields for left Wilms tumor include the lower portion of the heart and 2) to the interaction of doxorubicin and irradiation on cardiac muscle. It is recommended that doxorubicin dosage be sharply restricted in children with Wilms tumor of the left kidney who receive postoperative irradiation.
6292680	0	11	Doxorubicin	Chemical	D004317
6292680	12	26	cardiomyopathy	Disease	D009202
6292680	55	66	Wilms tumor	Disease	D009396
6292680	86	97	Wilms tumor	Disease	D009396
6292680	136	149	anthracycline	Chemical	D018943
6292680	150	164	cardiomyopathy	Disease	D009202
6292680	190	195	tumor	Disease	D009369
6292680	227	238	doxorubicin	Chemical	D004317
6292680	244	258	cardiomyopathy	Disease	D009202
6292680	319	330	Wilms tumor	Disease	D009396
6292680	399	410	doxorubicin	Chemical	D004317
6292680	469	480	doxorubicin	Chemical	D004317
6292680	527	538	Wilms tumor	Disease	D009396
6292680	CID	D004317	D009202

3969369|t|Promotional effects of testosterone and dietary fat on prostate carcinogenesis in genetically susceptible rats.
3969369|a|Germfree (GF) Lobund strain Wistar (LW) rats, fed vegetable diet L-485, have developed prostate adenocarcinomas spontaneously (10% incidence) at average age 34 months. Conventional LW rats, implanted with testosterone at age 4 months, developed a higher incidence of prostate cancer after an average interval of 14 months: 24% had developed gross tumors, and 40% when it included microscopic tumors. Preliminary results indicate that testosterone-treated LW rats that were fed the same diet, which was supplemented with corn oil up to 20% fat, developed prostate cancer after intervals of 6-12 months. Aged GF Sprague-Dawley (SD) rats have not developed prostate cancer spontaneously. Conventional SD rats fed diet L-485 and treated with testosterone developed only prostatitis. Experimental designs should consider genetic susceptibility as a basic prerequisite for studies on experimental prostate cancer.
3969369	23	35	testosterone	Chemical	D013739
3969369	64	78	carcinogenesis	Disease	D063646
3969369	199	223	prostate adenocarcinomas	Disease	D011471
3969369	317	329	testosterone	Chemical	D013739
3969369	379	394	prostate cancer	Disease	D011471
3969369	459	465	tumors	Disease	D009369
3969369	504	510	tumors	Disease	D009369
3969369	546	558	testosterone	Chemical	D013739
3969369	666	681	prostate cancer	Disease	D011471
3969369	766	781	prostate cancer	Disease	D011471
3969369	850	862	testosterone	Chemical	D013739
3969369	878	889	prostatitis	Disease	D011472
3969369	1003	1018	prostate cancer	Disease	D011471
3969369	CID	D013739	D011471
3969369	CID	D013739	D011472

3108839|t|Mitomycin C associated hemolytic uremic syndrome.
3108839|a|Mitomycin C associated Hemolytic Uremic Syndrome (HUS) is a potentially fatal but uncommon condition that is not yet widely recognised. It consists of microangiopathic hemolytic anemia, thrombocytopenia and progressive renal failure associated with mitomycin C treatment and affects about 10% of patients treated with this agent. The renal failure usually develops about 8-10 mth after start of mitomycin C treatment and the mortality is approximately 60% from renal failure or pulmonary edema. Renal lesions are similar to those seen in idiopathic HUS and include arteriolar fibrin thrombi, expanded subendothelial zones in glomerular capillary walls, ischemic wrinkling of glomerular basement membranes and mesangiolysis. The mechanism of action is postulated as mitomycin C-induced endothelial cell damage. We describe the clinical course and pathological findings in a 65 yr-old man with gastric adenocarcinoma who developed renal failure and thrombocytopenia while on treatment with mitomycin C and died in pulmonary edema.
3108839	0	11	Mitomycin C	Chemical	D016685
3108839	23	48	hemolytic uremic syndrome	Disease	D006463
3108839	50	61	Mitomycin C	Chemical	D016685
3108839	73	98	Hemolytic Uremic Syndrome	Disease	D006463
3108839	100	103	HUS	Disease	D006463
3108839	218	234	hemolytic anemia	Disease	D000743
3108839	236	252	thrombocytopenia	Disease	D013921
3108839	269	282	renal failure	Disease	D051437
3108839	299	310	mitomycin C	Chemical	D016685
3108839	384	397	renal failure	Disease	D051437
3108839	445	456	mitomycin C	Chemical	D016685
3108839	511	524	renal failure	Disease	D051437
3108839	528	543	pulmonary edema	Disease	D011654
3108839	545	558	Renal lesions	Disease	D051437
3108839	599	602	HUS	Disease	D006463
3108839	633	640	thrombi	Disease	D013927
3108839	703	711	ischemic	Disease	D007511
3108839	815	826	mitomycin C	Chemical	D016685
3108839	942	964	gastric adenocarcinoma	Disease	D013274
3108839	979	992	renal failure	Disease	D051437
3108839	997	1013	thrombocytopenia	Disease	D013921
3108839	1038	1049	mitomycin C	Chemical	D016685
3108839	1062	1077	pulmonary edema	Disease	D011654
3108839	CID	D016685	D051437
3108839	CID	D016685	D006463

2466960|t|Continuous ambulatory ECG monitoring during fluorouracil therapy: a prospective study.
2466960|a|Although there have been anecdotal reports of cardiac toxicity associated with fluorouracil (5-FU) therapy, this phenomenon has not been studied in a systematic fashion. We prospectively performed continuous ambulatory ECG monitoring on 25 patients undergoing 5-FU infusion for treatment of solid tumors in order to assess the incidence of ischemic ST changes. Patients were monitored for 23 +/- 4 hours before 5-FU infusion, and 98 +/- 9 hours during 5-FU infusion. Anginal episodes were rare: only one patient had angina (during 5-FU infusion). However, asymptomatic ST changes (greater than or equal to 1 mm ST deviation) were common: six of 25 patients (24%) had ST changes before 5-FU infusion v 17 (68%) during 5-FU infusion (P less than .002). The incidence of ischemic episodes per patient per hour was 0.05 +/- 0.02 prior to 5-FU infusion v 0.13 +/- 0.03 during 5-FU infusion (P less than .001); the duration of ECG changes was 0.6 +/- 0.3 minutes per patient per hour before 5-FU v 1.9 +/- 0.5 minutes per patient per hour during 5-FU (P less than .01). ECG changes were more common among patients with known coronary artery disease. There were two cases of sudden death, both of which occurred at the end of the chemotherapy course. We conclude that 5-FU infusion is associated with a significant increase in silent ST segment deviation suggestive of ischemia, particularly among patients with coronary artery disease. The mechanism and clinical significance of these ECG changes remain to be determined.
2466960	44	56	fluorouracil	Chemical	D005472
2466960	133	149	cardiac toxicity	Disease	D066126
2466960	166	178	fluorouracil	Chemical	D005472
2466960	180	184	5-FU	Chemical	D005472
2466960	347	351	5-FU	Chemical	D005472
2466960	384	390	tumors	Disease	D009369
2466960	427	435	ischemic	Disease	D007511
2466960	498	502	5-FU	Chemical	D005472
2466960	539	543	5-FU	Chemical	D005472
2466960	554	561	Anginal	Disease	D000787
2466960	603	609	angina	Disease	D000787
2466960	618	622	5-FU	Chemical	D005472
2466960	772	776	5-FU	Chemical	D005472
2466960	804	808	5-FU	Chemical	D005472
2466960	855	863	ischemic	Disease	D007511
2466960	921	925	5-FU	Chemical	D005472
2466960	958	962	5-FU	Chemical	D005472
2466960	1072	1076	5-FU	Chemical	D005472
2466960	1127	1131	5-FU	Chemical	D005472
2466960	1206	1229	coronary artery disease	Disease	D003324
2466960	1255	1267	sudden death	Disease	D003645
2466960	1348	1352	5-FU	Chemical	D005472
2466960	1449	1457	ischemia	Disease	D007511
2466960	1492	1515	coronary artery disease	Disease	D003324
2466960	CID	D005472	D000787
2466960	CID	D005472	D007511

2320800|t|Lethal anuria complicating high dose ifosfamide chemotherapy in a breast cancer patient with an impaired renal function.
2320800|a|A sixty-year-old woman with advanced breast cancer, previously treated with cisplatin, developed an irreversible lethal renal failure with anuria, the day after 5 g/m2 bolus ifosfamide. Postrenal failure was excluded by echography. A prerenal component could have contributed to renal failure because of a transient hypotension, due to an increasing ascitis, occurring just before anuria. However, correction of the hemodynamic parameters did not improve renal function. Ifosfamide is a known nephrotoxic drug with demonstrated tubulopathies. We strongly suspect that this lethal anuria was mainly due to ifosfamide, occurring in a patient having received previous cisplatin chemotherapy and with poor kidney perfusion due to transient hypotension. We recommend careful use of ifosfamide in patients pretreated with nephrotoxic chemotherapy and inadequate renal perfusion.
2320800	7	13	anuria	Disease	D001002
2320800	37	47	ifosfamide	Chemical	D007069
2320800	66	79	breast cancer	Disease	D001943
2320800	96	119	impaired renal function	Disease	D007674
2320800	158	171	breast cancer	Disease	D001943
2320800	197	206	cisplatin	Chemical	D002945
2320800	241	254	renal failure	Disease	D051437
2320800	260	266	anuria	Disease	D001002
2320800	295	305	ifosfamide	Chemical	D007069
2320800	307	324	Postrenal failure	Disease	D007674
2320800	400	413	renal failure	Disease	D051437
2320800	437	448	hypotension	Disease	D007022
2320800	502	508	anuria	Disease	D001002
2320800	592	602	Ifosfamide	Chemical	D007069
2320800	614	625	nephrotoxic	Disease	D007674
2320800	649	662	tubulopathies	Disease	D007674
2320800	701	707	anuria	Disease	D001002
2320800	726	736	ifosfamide	Chemical	D007069
2320800	786	795	cisplatin	Chemical	D002945
2320800	857	868	hypotension	Disease	D007022
2320800	898	908	ifosfamide	Chemical	D007069
2320800	937	948	nephrotoxic	Disease	D007674
2320800	CID	D007069	D007674
2320800	CID	D007069	D001002

2220369|t|Central vein thrombosis and topical dipivalyl epinephrine.
2220369|a|A report is given on an 83-year-old female who acquired central vein thrombosis in her seeing eye one day after having started topical medication with dipivalyl epinephrine for advanced glaucoma discovered in the other eye. From present knowledge about the effects of adrenergic eye drops on ocular blood circulation, it is difficult to suggest an association between the two events, which may be coincidental only.
2220369	8	23	vein thrombosis	Disease	D020246
2220369	36	57	dipivalyl epinephrine	Chemical	C015173
2220369	123	138	vein thrombosis	Disease	D020246
2220369	210	231	dipivalyl epinephrine	Chemical	C015173
2220369	245	253	glaucoma	Disease	D005901
2220369	CID	C015173	D020246

326460|t|Amelioration of bendrofluazide-induced hypokalemia by timolol.
326460|a|The beta adrenergic blocking drug, timolol, tended to correct the hypokalemia of short-term bendrofluazide treatment in 6 healthy male subjects and although the effect was small it was significant. Timolol also reduced the rise in plasma aldosterone and urine potassium excretion following bendrofluazide and increased the urine sodium/potassium ratio. There was no evidence of a shift of potassium from the intracellular to the extracellular space.
326460	16	30	bendrofluazide	Chemical	D001539
326460	39	50	hypokalemia	Disease	D007008
326460	54	61	timolol	Chemical	D013999
326460	98	105	timolol	Chemical	D013999
326460	129	140	hypokalemia	Disease	D007008
326460	155	169	bendrofluazide	Chemical	D001539
326460	261	268	Timolol	Chemical	D013999
326460	301	312	aldosterone	Chemical	D000450
326460	323	332	potassium	Chemical	D011188
326460	353	367	bendrofluazide	Chemical	D001539
326460	392	398	sodium	Chemical	D012964
326460	399	408	potassium	Chemical	D011188
326460	452	461	potassium	Chemical	D011188
326460	CID	D001539	D007008

20331935|t|A cross-sectional evaluation of the effect of risperidone and selective serotonin reuptake inhibitors on bone mineral density in boys.
20331935|a|OBJECTIVE: The aim of the present study was to investigate the effect of risperidone-induced hyperprolactinemia on trabecular bone mineral density (BMD) in children and adolescents. METHOD: Medically healthy 7- to 17-year-old males chronically treated, in a naturalistic setting, with risperidone were recruited for this cross-sectional study through child psychiatry outpatient clinics between November 2005 and June 2007. Anthropometric measurements and laboratory testing were conducted. The clinical diagnoses were based on chart review, and developmental and treatment history was obtained from the medical record. Volumetric BMD of the ultradistal radius was measured using peripheral quantitative computed tomography, and areal BMD of the lumbar spine was estimated using dual-energy x-ray absorptiometry. RESULTS: Hyperprolactinemia was present in 49% of 83 boys (n = 41) treated with risperidone for a mean of 2.9 years. Serum testosterone concentration increased with pubertal status but was not affected by hyperprolactinemia. As expected, bone mineral content and BMD increased with sexual maturity. After adjusting for the stage of sexual development and height and BMI z scores, serum prolactin was negatively associated with trabecular volumetric BMD at the ultradistal radius (P < .03). Controlling for relevant covariates, we also found treatment with selective serotonin reuptake inhibitors (SSRIs) to be associated with lower trabecular BMD at the radius (P = .03) and BMD z score at the lumbar spine (P < .05). These findings became more marked when the analysis was restricted to non-Hispanic white patients. Of 13 documented fractures, 3 occurred after risperidone and SSRIs were started, and none occurred in patients with hyperprolactinemia. CONCLUSIONS: This is the first study to link risperidone-induced hyperprolactinemia and SSRI treatment to lower BMD in children and adolescents. Future research should evaluate the longitudinal course of this adverse event to determine its temporal stability and whether a higher fracture rate ensues.
20331935	46	57	risperidone	Chemical	D018967
20331935	72	81	serotonin	Chemical	D012701
20331935	208	219	risperidone	Chemical	D018967
20331935	228	246	hyperprolactinemia	Disease	D006966
20331935	420	431	risperidone	Chemical	D018967
20331935	957	975	Hyperprolactinemia	Disease	D006966
20331935	1028	1039	risperidone	Chemical	D018967
20331935	1071	1083	testosterone	Chemical	D013739
20331935	1153	1171	hyperprolactinemia	Disease	D006966
20331935	1514	1523	serotonin	Chemical	D012701
20331935	1782	1791	fractures	Disease	D050723
20331935	1810	1821	risperidone	Chemical	D018967
20331935	1881	1899	hyperprolactinemia	Disease	D006966
20331935	1946	1957	risperidone	Chemical	D018967
20331935	1966	1984	hyperprolactinemia	Disease	D006966
20331935	CID	D018967	D006966

19707748|t|Seizures associated with levofloxacin: case presentation and literature review.
19707748|a|PURPOSE: We present a case of a patient who developed seizures shortly after initiating treatment with levofloxacin and to discuss the potential drug-drug interactions related to the inhibition of cytochrome P450 (CYP) 1A2 in this case, as well as in other cases, of levofloxacin-induced seizures. METHODS: Several biomedical databases were searched including MEDLINE, Cochrane and Ovid. The main search terms utilized were case report and levofloxacin. The search was limited to studies published in English. RESULTS: Six cases of levofloxacin-induced seizures have been reported in the literature. Drug-drug interactions related to the inhibition of CYP1A2 by levofloxacin are likely involved in the clinical outcome of these cases. CONCLUSIONS: Clinicians are exhorted to pay close attention when initiating levofloxacin therapy in patients taking medications with epileptogenic properties that are CYP1A2 substrates.
19707748	0	8	Seizures	Disease	D012640
19707748	25	37	levofloxacin	Chemical	D064704
19707748	134	142	seizures	Disease	D012640
19707748	183	195	levofloxacin	Chemical	D064704
19707748	347	359	levofloxacin	Chemical	D064704
19707748	368	376	seizures	Disease	D012640
19707748	520	532	levofloxacin	Chemical	D064704
19707748	612	624	levofloxacin	Chemical	D064704
19707748	633	641	seizures	Disease	D012640
19707748	742	754	levofloxacin	Chemical	D064704
19707748	891	903	levofloxacin	Chemical	D064704
19707748	CID	D064704	D012640

19692487|t|Mice lacking mPGES-1 are resistant to lithium-induced polyuria.
19692487|a|Cyclooxygenase-2 activity is required for the development of lithium-induced polyuria. However, the involvement of a specific, terminal prostaglandin (PG) isomerase has not been evaluated. The present study was undertaken to assess lithium-induced polyuria in mice deficient in microsomal prostaglandin E synthase-1 (mPGES-1). A 2-wk administration of LiCl (4 mmol.kg(-1).day(-1) ip) in mPGES-1 +/+ mice led to a marked polyuria with hyposmotic urine. This was associated with elevated renal mPGES-1 protein expression and increased urine PGE(2) excretion. In contrast, mPGES-1 -/- mice were largely resistant to lithium-induced polyuria and a urine concentrating defect, accompanied by nearly complete blockade of high urine PGE(2) and cAMP output. Immunoblotting, immunohistochemistry, and quantitative (q) RT-PCR consistently detected a significant decrease in aquaporin-2 (AQP2) protein expression in both the renal cortex and medulla of lithium-treated +/+ mice. This decrease was significantly attenuated in the -/- mice. qRT-PCR detected similar patterns of changes in AQP2 mRNA in the medulla but not in the cortex. Similarly, the total protein abundance of the Na-K-2Cl cotransporter (NKCC2) in the medulla but not in the cortex of the +/+ mice was significantly reduced by lithium treatment. In contrast, the dowregulation of renal medullary NKCC2 expression was significantly attenuated in the -/- mice. We conclude that mPGES-1-derived PGE(2) mediates lithium-induced polyuria likely via inhibition of AQP2 and NKCC2 expression.
19692487	38	45	lithium	Chemical	D008094
19692487	54	62	polyuria	Disease	D011141
19692487	125	132	lithium	Chemical	D008094
19692487	141	149	polyuria	Disease	D011141
19692487	200	213	prostaglandin	Chemical	D011453
19692487	215	217	PG	Chemical	D011453
19692487	296	303	lithium	Chemical	D008094
19692487	312	320	polyuria	Disease	D011141
19692487	353	368	prostaglandin E	Chemical	D011458
19692487	416	420	LiCl	Chemical	D018021
19692487	484	492	polyuria	Disease	D011141
19692487	603	609	PGE(2)	Chemical	D015232
19692487	677	684	lithium	Chemical	D008094
19692487	693	701	polyuria	Disease	D011141
19692487	790	796	PGE(2)	Chemical	D015232
19692487	1006	1013	lithium	Chemical	D008094
19692487	1234	1236	Na	Chemical	D012964
19692487	1237	1238	K	Chemical	D011188
19692487	1240	1242	Cl	Chemical	D002713
19692487	1347	1354	lithium	Chemical	D008094
19692487	1512	1518	PGE(2)	Chemical	D015232
19692487	1528	1535	lithium	Chemical	D008094
19692487	1544	1552	polyuria	Disease	D011141
19692487	CID	D018021	D011141

19289093|t|Identification of a simple and sensitive microplate method for the detection of oversulfated chondroitin sulfate in heparin products.
19289093|a|Heparin is a commonly implemented anticoagulant used to treat critically ill patients. Recently, a number of commercial lots of heparin products were found to be contaminated with an oversulfated chondroitin sulfate (OSCS) derivative that could elicit a hypotensive response in pigs following a single high-dose infusion. Using both contaminated heparin products and the synthetically produced derivative, we showed that the OSCS produces dose-dependent hypotension in pigs. The no observed effect level (NOEL) for this contaminant appears to be approximately 1mg/kg, corresponding to a contamination level of approximately 3%. We also demonstrated that OSCS can be identified in heparin products using a simple, inexpensive, commercially available heparin enzyme immunoassay (EIA) kit that has a limit of detection of approximately 0.1%, well below the NOEL. This kit may provide a useful method to test heparin products for contamination with oversulfated GAG derivatives.
19289093	93	112	chondroitin sulfate	Chemical	D002809
19289093	116	123	heparin	Chemical	D006493
19289093	134	141	Heparin	Chemical	D006493
19289093	262	269	heparin	Chemical	D006493
19289093	330	349	chondroitin sulfate	Chemical	D002809
19289093	388	399	hypotensive	Disease	D007022
19289093	480	487	heparin	Chemical	D006493
19289093	588	599	hypotension	Disease	D007022
19289093	814	821	heparin	Chemical	D006493
19289093	883	890	heparin	Chemical	D006493
19289093	1039	1046	heparin	Chemical	D006493
19289093	CID	D002809	D007022

18627295|t|Doxorubicin cardiomyopathy-induced inflammation and apoptosis are attenuated by gene deletion of the kinin B1 receptor.
18627295|a|Clinical use of the anthracycline doxorubicin (DOX) is limited by its cardiotoxic effects, which are attributed to the induction of apoptosis. To elucidate the possible role of the kinin B1 receptor (B1R) during the development of DOX cardiomyopathy, we studied B1R knockout mice (B1R(-/-)) by investigating cardiac inflammation and apoptosis after induction of DOX-induced cardiomyopathy. DOX control mice showed cardiac dysfunction measured by pressure-volume loops in vivo. This was associated with a reduced activation state of AKT, as well as an increased bax/bcl2 ratio in Western blots, indicating cardiac apoptosis. Furthermore, mRNA levels of the proinflammatory cytokine interleukin 6 were increased in the cardiac tissue. In DOX B1R(-/-) mice, cardiac dysfunction was improved compared to DOX control mice, which was associated with normalization of the bax/bcl-2 ratio and interleukin 6, as well as AKT activation state. These findings suggest that B1R is detrimental in DOX cardiomyopathy in that it mediates the inflammatory response and apoptosis. These insights might have useful implications for future studies utilizing B1R antagonists for treatment of human DOX cardiomyopathy.
18627295	0	11	Doxorubicin	Chemical	D004317
18627295	12	26	cardiomyopathy	Disease	D009202
18627295	35	47	inflammation	Disease	D007249
18627295	140	153	anthracycline	Chemical	D018943
18627295	154	165	doxorubicin	Chemical	D004317
18627295	167	170	DOX	Chemical	D004317
18627295	190	201	cardiotoxic	Disease	D066126
18627295	351	354	DOX	Chemical	D004317
18627295	355	369	cardiomyopathy	Disease	D009202
18627295	436	448	inflammation	Disease	D007249
18627295	482	485	DOX	Chemical	D004317
18627295	494	508	cardiomyopathy	Disease	D009202
18627295	510	513	DOX	Chemical	D004317
18627295	534	553	cardiac dysfunction	Disease	D006331
18627295	725	742	cardiac apoptosis	Disease	D006331
18627295	856	859	DOX	Chemical	D004317
18627295	875	894	cardiac dysfunction	Disease	D006331
18627295	920	923	DOX	Chemical	D004317
18627295	1103	1106	DOX	Chemical	D004317
18627295	1107	1121	cardiomyopathy	Disease	D009202
18627295	1297	1300	DOX	Chemical	D004317
18627295	1301	1315	cardiomyopathy	Disease	D009202
18627295	CID	D004317	D009202

18405372|t|Hepatotoxicity associated with sulfasalazine in inflammatory arthritis: A case series from a local surveillance of serious adverse events.
18405372|a|BACKGROUND: Spontaneous reporting systems for adverse drug reactions (ADRs) are handicapped by under-reporting and limited detail on individual cases. We report an investigation from a local surveillance for serious adverse drug reactions associated with disease modifying anti-rheumatic drugs that was triggered by the occurrence of liver failure in two of our patients. METHODS: Serious ADR reports have been solicited from local clinicians by regular postcards over the past seven years. Patients', who had hepatotoxicity on sulfasalazine and met a definition of a serious ADR, were identified. Two clinicians reviewed structured case reports and assessed causality by consensus and by using a causality assessment instrument. The likely frequency of hepatotoxicity with sulfasalazine was estimated by making a series of conservative assumptions. RESULTS: Ten cases were identified: eight occurred during surveillance. Eight patients were hospitalised, two in hepatic failure - one died after a liver transplant. All but one event occurred within 6 weeks of treatment. Seven patients had a skin rash, three eosinophilia and one interstitial nephritis. Five patients were of Black British of African or Caribbean descent. Liver enzymes showed a hepatocellular pattern in four cases and a mixed pattern in six. Drug-related hepatotoxicity was judged probable or highly probable in 8 patients. The likely frequency of serious hepatotoxicity with sulfasalazine was estimated at 0.4% of treated patients. CONCLUSION: Serious hepatotoxicity associated with sulfasalazine appears to be under-appreciated and intensive monitoring and vigilance in the first 6 weeks of treatment is especially important.
18405372	0	14	Hepatotoxicity	Disease	D056486
18405372	31	44	sulfasalazine	Chemical	D012460
18405372	61	70	arthritis	Disease	D001168
18405372	473	486	liver failure	Disease	D017093
18405372	649	663	hepatotoxicity	Disease	D056486
18405372	667	680	sulfasalazine	Chemical	D012460
18405372	893	907	hepatotoxicity	Disease	D056486
18405372	913	926	sulfasalazine	Chemical	D012460
18405372	1102	1117	hepatic failure	Disease	D017093
18405372	1232	1241	skin rash	Disease	D005076
18405372	1249	1261	eosinophilia	Disease	D004802
18405372	1270	1292	interstitial nephritis	Disease	D009395
18405372	1464	1478	hepatotoxicity	Disease	D056486
18405372	1565	1579	hepatotoxicity	Disease	D056486
18405372	1585	1598	sulfasalazine	Chemical	D012460
18405372	1662	1676	hepatotoxicity	Disease	D056486
18405372	1693	1706	sulfasalazine	Chemical	D012460
18405372	CID	D012460	D056486

18356633|t|An evaluation of amikacin nephrotoxicity in the hematology/oncology population.
18356633|a|Amikacin is an aminoglycoside commonly used to provide empirical double gram-negative treatment for febrile neutropenia and other suspected infections. Strategies of extended-interval and conventional dosing have been utilized extensively in the general medical population; however, data are lacking to support a dosing strategy in the hematology/oncology population. To evaluate amikacin-associated nephrotoxicity in an adult hematology/oncology population, a prospective, randomized, open-label trial was conducted at a university-affiliated medical center. Forty patients with a diagnosis consistent with a hematologic/oncologic disorder that required treatment with an aminoglycoside were randomized to either conventional or extended-interval amikacin. The occurrence of nephrotoxicity by means of an increase in serum creatinine and evaluation of efficacy via amikacin serum concentrations with respective pathogens were assessed. The occurrence of nephrotoxicity was similar between the conventional and extended-interval groups, at 10% and 5%, respectively (P = 1.00). Six patients in the conventional group had a positive culture, compared with none in the extended-interval group (P = 0.002). The occurrence of nephrotoxicity was similar between the two dosing regimens, but the distribution of risk factors was variable between the two groups. Efficacy could not be assessed.
18356633	17	25	amikacin	Chemical	D000583
18356633	26	40	nephrotoxicity	Disease	D007674
18356633	80	88	Amikacin	Chemical	D000583
18356633	95	109	aminoglycoside	Chemical	D000617
18356633	180	199	febrile neutropenia	Disease	D009503
18356633	220	230	infections	Disease	D007239
18356633	460	468	amikacin	Chemical	D000583
18356633	480	494	nephrotoxicity	Disease	D007674
18356633	690	720	hematologic/oncologic disorder	Disease	D006402|D009369	hematologic disorder|oncologic disorder
18356633	753	767	aminoglycoside	Chemical	D000617
18356633	828	836	amikacin	Chemical	D000583
18356633	856	870	nephrotoxicity	Disease	D007674
18356633	904	914	creatinine	Chemical	D003404
18356633	946	954	amikacin	Chemical	D000583
18356633	1035	1049	nephrotoxicity	Disease	D007674
18356633	1301	1315	nephrotoxicity	Disease	D007674
18356633	CID	D000583	D007674

16574713|t|Memory function and serotonin transporter promoter gene polymorphism in ecstasy (MDMA) users.
16574713|a|Although 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) has been shown to damage brain serotonin (5-HT) neurons in animals and possibly humans, little is known about the long-term consequences of MDMA-induced 5-HT neurotoxic lesions on functions in which 5-HT is involved, such as cognitive function. Because 5-HT transporters play a key element in the regulation of synaptic 5-HT transmission it may be important to control for the potential covariance effect of a polymorphism in the 5-HT transporter promoter gene region (5-HTTLPR) when studying the effects of MDMA as well as cognitive functioning. The aim of the study was to investigate the effects of moderate and heavy MDMA use on cognitive function, as well as the effects of long-term abstention from MDMA, in subjects genotyped for 5-HTTLPR. A second aim of the study was to determine whether these effects differ for females and males. Fifteen moderate MDMA users (<55 lifetime tablets), 22 heavy MDMA+ users (>55 lifetime tablets), 16 ex-MDMA+ users (last tablet > 1 year ago) and 13 controls were compared on a battery of neuropsychological tests. DNA from peripheral nuclear blood cells was genotyped for 5-HTTLPR using standard polymerase chain reaction methods.A significant group effect was observed only on memory function tasks (p = 0.04) but not on reaction times (p = 0.61) or attention/executive functioning (p = 0.59). Heavy and ex-MDMA+ users performed significantly poorer on memory tasks than controls. In contrast, no evidence of memory impairment was observed in moderate MDMA users. No significant effect of 5-HTTLPR or gender was observed. While the use of MDMA in quantities that may be considered "moderate" is not associated with impaired memory functioning, heavy use of MDMA use may lead to long lasting memory impairments. No effect of 5-HTTLPR or gender on memory function or MDMA use was observed.
16574713	20	29	serotonin	Chemical	D012701
16574713	72	79	ecstasy	Chemical	D018817
16574713	81	85	MDMA	Chemical	D018817
16574713	103	136	3,4-methylenedioxymethamphetamine	Chemical	D018817
16574713	138	142	MDMA	Chemical	D018817
16574713	146	153	ecstasy	Chemical	D018817
16574713	186	195	serotonin	Chemical	D012701
16574713	197	201	5-HT	Chemical	D012701
16574713	295	299	MDMA	Chemical	D018817
16574713	308	312	5-HT	Chemical	D012701
16574713	313	331	neurotoxic lesions	Disease	D020258
16574713	354	358	5-HT	Chemical	D012701
16574713	408	412	5-HT	Chemical	D012701
16574713	475	479	5-HT	Chemical	D012701
16574713	585	589	5-HT	Chemical	D012701
16574713	663	667	MDMA	Chemical	D018817
16574713	776	780	MDMA	Chemical	D018817
16574713	860	864	MDMA	Chemical	D018817
16574713	1014	1018	MDMA	Chemical	D018817
16574713	1058	1062	MDMA	Chemical	D018817
16574713	1100	1104	MDMA	Chemical	D018817
16574713	1505	1509	MDMA	Chemical	D018817
16574713	1607	1624	memory impairment	Disease	D008569
16574713	1650	1654	MDMA	Chemical	D018817
16574713	1737	1741	MDMA	Chemical	D018817
16574713	1813	1840	impaired memory functioning	Disease	D008569
16574713	1855	1859	MDMA	Chemical	D018817
16574713	1889	1907	memory impairments	Disease	D008569
16574713	1963	1967	MDMA	Chemical	D018817
16574713	CID	D018817	D008569

15638391|t|Aging process of epithelial cells of the rat prostate lateral lobe in experimental hyperprolactinemia induced by haloperidol.
15638391|a|The aim of the study was to examine the influence of hyperprolactinemia, induced by haloperidol (HAL) on age related morphology and function changes of epithelial cells in rat prostate lateral lobe. The study was performed on sexually mature male rats. Serum concentrations of prolactin (PRL) and testosterone (T) were measured. Tissue sections were evaluated with light and electron microscopy. Immunohistochemical reactions for Anti-Proliferating Cell Nuclear Antigen (PCNA) were performed. In rats of the experimental group, the mean concentration of: PRL was more than twice higher, whereas T concentration was almost twice lower than that in the control group. Light microscopy visualized the following: hypertrophy and epithelium hyperplasia of the glandular ducts, associated with increased PCNA expression. Electron microscopy revealed changes in columnar epithelial cells, concerning organelles, engaged in protein synthesis and secretion.
15638391	83	101	hyperprolactinemia	Disease	D006966
15638391	113	124	haloperidol	Chemical	D006220
15638391	179	197	hyperprolactinemia	Disease	D006966
15638391	210	221	haloperidol	Chemical	D006220
15638391	223	226	HAL	Chemical	D006220
15638391	414	417	PRL	Chemical	D011388
15638391	423	435	testosterone	Chemical	D013739
15638391	437	438	T	Chemical	D013739
15638391	681	684	PRL	Chemical	D011388
15638391	721	722	T	Chemical	D013739
15638391	835	846	hypertrophy	Disease	D006984
15638391	862	873	hyperplasia	Disease	D006965
15638391	CID	D006220	D006966

15531665|t|Does supplemental vitamin C increase cardiovascular disease risk in women with diabetes?
15531665|a|BACKGROUND: Vitamin C acts as a potent antioxidant; however, it can also be a prooxidant and glycate protein under certain circumstances in vitro. These observations led us to hypothesize that a high intake of vitamin C in diabetic persons might promote atherosclerosis. OBJECTIVE: The objective was to examine the relation between vitamin C intake and mortality from cardiovascular disease. DESIGN: We studied the relation between vitamin C intake and mortality from total cardiovascular disease (n = 281), coronary artery disease (n = 175), and stroke (n = 57) in 1923 postmenopausal women who reported being diabetic at baseline. Diet was assessed with a food-frequency questionnaire at baseline, and subjects initially free of coronary artery disease were prospectively followed for 15 y. RESULTS: After adjustment for cardiovascular disease risk factors, type of diabetes medication used, duration of diabetes, and intakes of folate, vitamin E, and beta-carotene, the adjusted relative risks of total cardiovascular disease mortality were 1.0, 0.97, 1.11, 1.47, and 1.84 (P for trend < 0.01) across quintiles of total vitamin C intake from food and supplements. Adjusted relative risks of coronary artery disease were 1.0, 0.81, 0.99, 1.26, and 1.91 (P for trend = 0.01) and of stroke were 1.0, 0.52, 1.23, 2.22, and 2.57 (P for trend < 0.01). When dietary and supplemental vitamin C were analyzed separately, only supplemental vitamin C showed a positive association with mortality endpoints. Vitamin C intake was unrelated to mortality from cardiovascular disease in the nondiabetic subjects at baseline. CONCLUSION: A high vitamin C intake from supplements is associated with an increased risk of cardiovascular disease mortality in postmenopausal women with diabetes.
15531665	18	27	vitamin C	Chemical	D001205
15531665	37	59	cardiovascular disease	Disease	D002318
15531665	79	87	diabetes	Disease	D003920
15531665	101	110	Vitamin C	Chemical	D001205
15531665	299	308	vitamin C	Chemical	D001205
15531665	312	320	diabetic	Disease	D003920
15531665	343	358	atherosclerosis	Disease	D050197
15531665	421	430	vitamin C	Chemical	D001205
15531665	457	479	cardiovascular disease	Disease	D002318
15531665	521	530	vitamin C	Chemical	D001205
15531665	563	585	cardiovascular disease	Disease	D002318
15531665	597	620	coronary artery disease	Disease	D003324
15531665	636	642	stroke	Disease	D020521
15531665	700	708	diabetic	Disease	D003920
15531665	820	843	coronary artery disease	Disease	D003324
15531665	912	934	cardiovascular disease	Disease	D002318
15531665	957	965	diabetes	Disease	D003920
15531665	995	1003	diabetes	Disease	D003920
15531665	1020	1026	folate	Chemical	D005492
15531665	1028	1037	vitamin E	Chemical	D014810
15531665	1043	1056	beta-carotene	Chemical	D019207
15531665	1095	1117	cardiovascular disease	Disease	D002318
15531665	1212	1221	vitamin C	Chemical	D001205
15531665	1283	1306	coronary artery disease	Disease	D003324
15531665	1372	1378	stroke	Disease	D020521
15531665	1468	1477	vitamin C	Chemical	D001205
15531665	1522	1531	vitamin C	Chemical	D001205
15531665	1588	1597	Vitamin C	Chemical	D001205
15531665	1637	1659	cardiovascular disease	Disease	D002318
15531665	1720	1729	vitamin C	Chemical	D001205
15531665	1794	1816	cardiovascular disease	Disease	D002318
15531665	1856	1864	diabetes	Disease	D003920
15531665	CID	D001205	D002318

12851669|t|Absolute and attributable risk of venous thromboembolism in women on combined cyproterone acetate and ethinylestradiol.
12851669|a|OBJECTIVE: To achieve absolute risk estimates of venous thromboembolism (VTE) among women on cyproterone acetate plus ethinylestradiol (CPA/EE), and among women on combined oral contraceptives (COCs). METHODS: From the Danish National Register of Patients (NRP), 1996 to 1998, the records of 1.1 million Danish women, ages 15 to 44 years, were searched for evidence of VTE. COC use was ascertained through mailed questionnaires. Sales statistics of COCs and CPA/EE were provided through Danish Drug Statistics. RESULTS: During the time frame of the study, 330 women were found to have had VTE while on COCs. Of these women, 67 were on levonorgestrel-containing COCs. Eleven were on CPA/EE. The corresponding absolute risk of VTE was 3.4 (range, 3.1-3.8) per 10 000 women years among the women on COCs, 4.2 (range, 3.2-5.2) per 10 000 women years among women on levonorgestrel-containing COCs, and 3.1 (range, 1.3-4.9) per 10 000 women years among the women on CPA/EE. CONCLUSION: Our results suggest the absolute risk of VTE among Danish women on COCs is similar to that among women taking CPA/EE.
12851669	34	56	venous thromboembolism	Disease	D054556
12851669	78	97	cyproterone acetate	Chemical	D017373
12851669	102	118	ethinylestradiol	Chemical	D004997
12851669	169	191	venous thromboembolism	Disease	D054556
12851669	193	196	VTE	Disease	D054556
12851669	213	232	cyproterone acetate	Chemical	D017373
12851669	238	254	ethinylestradiol	Chemical	D004997
12851669	256	259	CPA	Chemical	D017373
12851669	260	262	EE	Chemical	D004997
12851669	284	312	combined oral contraceptives	Chemical	D003277
12851669	314	318	COCs	Chemical	D003277
12851669	489	492	VTE	Disease	D054556
12851669	494	497	COC	Chemical	D003277
12851669	569	573	COCs	Chemical	D003277
12851669	578	581	CPA	Chemical	D017373
12851669	582	584	EE	Chemical	D004997
12851669	709	712	VTE	Disease	D054556
12851669	722	726	COCs	Chemical	D003277
12851669	755	769	levonorgestrel	Chemical	D016912
12851669	781	785	COCs	Chemical	D003277
12851669	802	805	CPA	Chemical	D017373
12851669	806	808	EE	Chemical	D004997
12851669	845	848	VTE	Disease	D054556
12851669	916	920	COCs	Chemical	D003277
12851669	981	995	levonorgestrel	Chemical	D016912
12851669	1007	1011	COCs	Chemical	D003277
12851669	1080	1083	CPA	Chemical	D017373
12851669	1084	1086	EE	Chemical	D004997
12851669	1141	1144	VTE	Disease	D054556
12851669	1167	1171	COCs	Chemical	D003277
12851669	1210	1213	CPA	Chemical	D017373
12851669	1214	1216	EE	Chemical	D004997
12851669	CID	D003277	D054556

12842176|t|Effect of lindane on hepatic and brain cytochrome P450s and influence of P450 modulation in lindane induced neurotoxicity.
12842176|a|Oral administration of lindane (2.5, 5, 10 and 15 mg/kg, body weight) for 5 days was found to produce a dose-dependent increase in the activity of P450 dependent 7-ethoxyresorufin-O-deethylase (EROD), 7-pentoxyresorufin-O-dealkylase (PROD) and N-nitrosodimethylamine demethylase (NDMA-d) in rat brain and liver. A significant increase in the hepatic and brain P450 monooxygenases was also observed when the duration of exposure of low dose (2.5 mg/kg) of lindane was increased from 5 days to 15 or 21 days. As observed with different doses, the magnitude of induction in the activity of P450 monooxygenases was several fold higher in liver microsomes when compared with the brain. Western blotting studies have indicated that the increase in the P450 enzymes could be due to the increase in the expression of P450 1A1/1A2, 2B1/2B2 and 2E1 isoenzymes. In vitro studies using organic inhibitors specific for individual P450 isoenzymes and antibody inhibition experiments have further demonstrated that the increase in the activity of PROD, EROD and NDMA-d are due to the increase in the levels of P450 2B1/2B2, 1A1/1A2 and 2E1 isoenzymes, respectively. Induction studies have further shown that while pretreatment of 3-methylcholanthrene (MC), an inducer of P4501A1/1A2, did not produce any significant effect in the incidence of lindane induced convulsions, pretreatment with phenobarbital (PB), an inducer of P450 2B1/2B2 or ethanol, an inducer of P450 2E1 catalysed reactions, significantly increased the incidence of lindane induced convulsions. Similarly, when the P450-mediated metabolism of lindane was blocked by cobalt chloride incidence of convulsions was increased in animals treated with lindane indicating that lindane per se or its metabolites formed by PB or ethanol inducible P450 isoenzymes are involved in its neurobehavioral toxicity.
12842176	10	17	lindane	Chemical	D001556
12842176	92	99	lindane	Chemical	D001556
12842176	108	121	neurotoxicity	Disease	D020258
12842176	146	153	lindane	Chemical	D001556
12842176	367	389	N-nitrosodimethylamine	Chemical	D004128
12842176	403	407	NDMA	Chemical	D004128
12842176	578	585	lindane	Chemical	D001556
12842176	1170	1174	NDMA	Chemical	D004128
12842176	1338	1358	3-methylcholanthrene	Chemical	D008748
12842176	1360	1362	MC	Chemical	D008748
12842176	1451	1458	lindane	Chemical	D001556
12842176	1467	1478	convulsions	Disease	D012640
12842176	1498	1511	phenobarbital	Chemical	D010634
12842176	1548	1555	ethanol	Chemical	D000431
12842176	1642	1649	lindane	Chemical	D001556
12842176	1658	1669	convulsions	Disease	D012640
12842176	1719	1726	lindane	Chemical	D001556
12842176	1742	1757	cobalt chloride	Chemical	C018021
12842176	1771	1782	convulsions	Disease	D012640
12842176	1821	1828	lindane	Chemical	D001556
12842176	1845	1852	lindane	Chemical	D001556
12842176	1895	1902	ethanol	Chemical	D000431
12842176	1965	1973	toxicity	Disease	D064420
12842176	CID	D001556	D012640

12745515|t|Seizure associated with sleep deprivation and sustained-release bupropion.
12745515|a|This case report describes a generalized seizure associated with sustained-release bupropion use and sleep deprivation. The subject, a 31-year-old female smoker, was participating in a clinical trial evaluating an investigational medication for smoking cessation that used sustained-release bupropion as an active control. After 5 weeks of bupropion use, the subject experienced a generalized tonic clonic seizure after staying up nearly all night packing and moving to a new residence. The patient had no other risk factors for seizures. We suggest that sleep deprivation may add to the risk of bupropion-associated seizures.
12745515	0	7	Seizure	Disease	D012640
12745515	24	41	sleep deprivation	Disease	D012892
12745515	64	73	bupropion	Chemical	D016642
12745515	116	123	seizure	Disease	D012640
12745515	158	167	bupropion	Chemical	D016642
12745515	176	193	sleep deprivation	Disease	D012892
12745515	366	375	bupropion	Chemical	D016642
12745515	415	424	bupropion	Chemical	D016642
12745515	481	488	seizure	Disease	D012640
12745515	604	612	seizures	Disease	D012640
12745515	630	647	sleep deprivation	Disease	D012892
12745515	671	680	bupropion	Chemical	D016642
12745515	692	700	seizures	Disease	D012640
12745515	CID	D016642	D012640

12571256|t|Nephrotoxic effects in high-risk patients undergoing angiography.
12571256|a|BACKGROUND: The use of iodinated contrast medium can result in nephropathy. Whether iso-osmolar contrast medium is less nephrotoxic than low-osmolar contrast medium in high-risk patients is uncertain. METHODS: We conducted a randomized, double-blind, prospective, multicenter study comparing the nephrotoxic effects of an iso-osmolar, dimeric, nonionic contrast medium, iodixanol, with those of a low-osmolar, nonionic, monomeric contrast medium, iohexol. The study involved 129 patients with diabetes with serum creatinine concentrations of 1.5 to 3.5 mg per deciliter who underwent coronary or aortofemoral angiography. The primary end point was the peak increase from base line in the creatinine concentration during the three days after angiography. Other end points were an increase in the creatinine concentration of 0.5 mg per deciliter or more, an increase of 1.0 mg per deciliter or more, and a change in the creatinine concentration from day 0 to day 7. RESULTS: The creatinine concentration increased significantly less in patients who received iodixanol. From day 0 to day 3, the mean peak increase in creatinine was 0.13 mg per deciliter in the iodixanol group and 0.55 mg per deciliter in the iohexol group (P=0.001; the increase with iodixanol minus the increase with iohexol, -0.42 mg per deciliter [95 percent confidence interval, -0.73 to -0.22]). Two of the 64 patients in the iodixanol group (3 percent) had an increase in the creatinine concentration of 0.5 mg per deciliter or more, as compared with 17 of the 65 patients in the iohexol group (26 percent) (P=0.002; odds ratio for such an increase in the iodixanol group, 0.09 [95 percent confidence interval, 0.02 to 0.41]). No patient receiving iodixanol had an increase of 1.0 mg per deciliter or more, but 10 patients in the iohexol group (15 percent) did. The mean change in the creatinine concentration from day 0 to day 7 was 0.07 mg per deciliter in the iodixanol group and 0.24 mg per deciliter in the iohexol group (P=0.003; value in the iodixanol group minus the value in the iohexol group, -0.17 mg per deciliter [95 percent confidence interval, -0.34 to -0.07]). CONCLUSIONS: Nephropathy induced by contrast medium may be less likely to develop in high-risk patients when iodixanol is used rather than a low-osmolar, nonionic contrast medium.
12571256	0	11	Nephrotoxic	Disease	D007674
12571256	129	140	nephropathy	Disease	D007674
12571256	186	197	nephrotoxic	Disease	D007674
12571256	362	373	nephrotoxic	Disease	D007674
12571256	436	445	iodixanol	Chemical	C044834
12571256	513	520	iohexol	Chemical	D007472
12571256	559	567	diabetes	Disease	D003920
12571256	579	589	creatinine	Chemical	D003404
12571256	754	764	creatinine	Chemical	D003404
12571256	861	871	creatinine	Chemical	D003404
12571256	984	994	creatinine	Chemical	D003404
12571256	1043	1053	creatinine	Chemical	D003404
12571256	1122	1131	iodixanol	Chemical	C044834
12571256	1180	1190	creatinine	Chemical	D003404
12571256	1224	1233	iodixanol	Chemical	C044834
12571256	1273	1280	iohexol	Chemical	D007472
12571256	1315	1324	iodixanol	Chemical	C044834
12571256	1349	1356	iohexol	Chemical	D007472
12571256	1462	1471	iodixanol	Chemical	C044834
12571256	1513	1523	creatinine	Chemical	D003404
12571256	1617	1624	iohexol	Chemical	D007472
12571256	1693	1702	iodixanol	Chemical	C044834
12571256	1785	1794	iodixanol	Chemical	C044834
12571256	1867	1874	iohexol	Chemical	D007472
12571256	1922	1932	creatinine	Chemical	D003404
12571256	2000	2009	iodixanol	Chemical	C044834
12571256	2049	2056	iohexol	Chemical	D007472
12571256	2086	2095	iodixanol	Chemical	C044834
12571256	2125	2132	iohexol	Chemical	D007472
12571256	2227	2238	Nephropathy	Disease	D007674
12571256	2323	2332	iodixanol	Chemical	C044834
12571256	CID	D007472	D007674

9514561|t|Experimental cranial pain elicited by capsaicin: a PET study.
9514561|a|Using a positron emission tomography (PET) study it was shown recently that in migraine without aura certain areas in the brain stem were activated during the headache state, but not in the headache free interval. It was suggested that this brain stem activation is inherent to the migraine attack itself and represents the so called 'migraine generator'. To test this hypothesis we performed an experimental pain study in seven healthy volunteers, using the same positioning in the PET scanner as in the migraine patients. A small amount of capsaicin was administered subcutaneously in the right forehead to evoke a burning painful sensation in the first division of the trigeminal nerve. Increases of regional cerebral blood flow (rCBF) were found bilaterally in the insula, in the anterior cingulate cortex, the cavernous sinus and the cerebellum. Using the same stereotactic space limits as in the above mentioned migraine study no brain stem activation was found in the acute pain state compared to the pain free state. The increase of activation in the region of the cavernous sinus however, suggests that this structure is more likely to be involved in trigeminal transmitted pain as such, rather than in a specific type of headache as was suggested for cluster headache.
9514561	21	25	pain	Disease	D010146
9514561	38	47	capsaicin	Chemical	D002211
9514561	141	149	migraine	Disease	D008881
9514561	221	229	headache	Disease	D006261
9514561	252	260	headache	Disease	D006261
9514561	344	352	migraine	Disease	D008881
9514561	397	405	migraine	Disease	D008881
9514561	471	475	pain	Disease	D010146
9514561	567	575	migraine	Disease	D008881
9514561	604	613	capsaicin	Chemical	D002211
9514561	687	694	painful	Disease	D010146
9514561	980	988	migraine	Disease	D008881
9514561	1043	1047	pain	Disease	D010146
9514561	1070	1074	pain	Disease	D010146
9514561	1245	1249	pain	Disease	D010146
9514561	1293	1301	headache	Disease	D006261
9514561	1323	1339	cluster headache	Disease	D003027
9514561	CID	D002211	D010146

9165568|t|Neuroleptic malignant syndrome with risperidone.
9165568|a|Neuroleptic malignant syndrome is thought to be a result of dopamine D2 receptor blockade in the striatum of the basal ganglia. Risperidone, a benzisoxazole derivative antipsychotic, has high serotonin 5-HT2 receptor blockade and dose-related D2 receptor blockade. The high ratio is believed to impart the low frequency of extrapyramidal symptoms with risperidone at low dosages. With this low frequency of extrapyramidal symptoms, it was thought the frequency of neuroleptic malignant syndrome might also be lowered. A 73-year-old woman developed neuroleptic malignant syndrome after monotherapy with risperidone. The syndrome reversed after discontinuing risperidone and starting treatment with dantrolene and bromocriptine. It appears that the protection from extrapyramidal side effects observed with risperidone does not ensure protection from neuroleptic malignant syndrome.
9165568	0	30	Neuroleptic malignant syndrome	Disease	D009459
9165568	36	47	risperidone	Chemical	D018967
9165568	49	79	Neuroleptic malignant syndrome	Disease	D009459
9165568	109	117	dopamine	Chemical	D004298
9165568	177	188	Risperidone	Chemical	D018967
9165568	192	205	benzisoxazole	Chemical	C441200
9165568	241	250	serotonin	Chemical	D012701
9165568	372	395	extrapyramidal symptoms	Disease	D001480
9165568	401	412	risperidone	Chemical	D018967
9165568	456	479	extrapyramidal symptoms	Disease	D001480
9165568	513	543	neuroleptic malignant syndrome	Disease	D009459
9165568	597	627	neuroleptic malignant syndrome	Disease	D009459
9165568	651	662	risperidone	Chemical	D018967
9165568	706	717	risperidone	Chemical	D018967
9165568	746	756	dantrolene	Chemical	D003620
9165568	761	774	bromocriptine	Chemical	D001971
9165568	854	865	risperidone	Chemical	D018967
9165568	898	928	neuroleptic malignant syndrome	Disease	D009459
9165568	CID	D018967	D009459

9154656|t|Hepatic and extrahepatic angiotensinogen gene expression in rats with acute nephrotic syndrome.
9154656|a|Plasma concentration and urine excretion of the renin-angiotensin system proteins are altered in rats with nephrotic syndrome (NS). In this work the messenger ribonucleic acid (mRNA) levels of angiotensinogen (Ao) were analyzed with the slot-blot hybridization technique in liver and other extrahepatic tissues: kidney, heart, brain, and adrenal gland from control, nephrotic, and pair-fed (PF) rats. NS was induced by a single injection of puromycin amino-nucleoside (PAN). Although a great urinary excretion and half-normal plasma levels of Ao were observed on day 6 after PAN injection, when NS was clearly established, hepatic Ao mRNA levels did not change. Furthermore, the Ao mRNA levels did not change in any of the extrahepatic tissues studied on day 6, nor did its hepatic levels at days 1, 3, 5, or 7 after PAN injection. These data suggest that the hepatic and extrahepatic Ao mRNA levels are unaltered during the development of the acute NS induced by PAN.
9154656	76	94	nephrotic syndrome	Disease	D009404
9154656	150	161	angiotensin	Chemical	D000809
9154656	203	221	nephrotic syndrome	Disease	D009404
9154656	223	225	NS	Disease	D009404
9154656	462	471	nephrotic	Disease	D009404
9154656	497	499	NS	Disease	D009404
9154656	537	563	puromycin amino-nucleoside	Chemical	D011692
9154656	565	568	PAN	Chemical	D011692
9154656	671	674	PAN	Chemical	D011692
9154656	691	693	NS	Disease	D009404
9154656	913	916	PAN	Chemical	D011692
9154656	1046	1048	NS	Disease	D009404
9154656	1060	1063	PAN	Chemical	D011692
9154656	CID	D011692	D009404

8911359|t|Cyclophosphamide associated bladder cancer--a highly aggressive disease: analysis of 12 cases.
8911359|a|PURPOSE: We gained knowledge of the etiology, treatment and prevention of cyclophosphamide associated urothelial cancer. MATERIALS AND METHODS: The medical records of 6 men and 6 women (mean age 55 years) with cyclophosphamide associated bladder cancer were reviewed. RESULTS: All tumors were grade 3 or 4 transitional cell carcinoma. Of the 5 patients initially treated with endoscopic resection alone only 1 is alive without disease. Of the 6 patients who underwent early cystectomy 4 were alive at 24 to 111 months. The remaining patient with extensive cancer underwent partial cystectomy for palliation and died 3 months later. CONCLUSIONS: Cyclophosphamide associated bladder tumor is an aggressive disease. However, long-term survival is possible when radical cystectomy is performed for bladder tumors with any sign of invasion and for recurrent high grade disease, even when noninvasive.
8911359	0	16	Cyclophosphamide	Chemical	D003520
8911359	28	42	bladder cancer	Disease	D001749
8911359	169	185	cyclophosphamide	Chemical	D003520
8911359	197	214	urothelial cancer	Disease	D014523
8911359	305	321	cyclophosphamide	Chemical	D003520
8911359	333	347	bladder cancer	Disease	D001749
8911359	376	382	tumors	Disease	D009369
8911359	419	428	carcinoma	Disease	D002277
8911359	651	657	cancer	Disease	D009369
8911359	740	756	Cyclophosphamide	Chemical	D003520
8911359	768	781	bladder tumor	Disease	D001749
8911359	889	903	bladder tumors	Disease	D001749
8911359	CID	D003520	D001749

8686832|t|Leg and back pain after spinal anaesthesia involving hyperbaric 5% lignocaine.
8686832|a|Fifty-four patients, aged 27-90 years, who were given lignocaine 5% in 6.8% glucose solution for spinal anaesthesia were studied. Thirteen of these patients experienced pain in the legs and/or back after recovery from anaesthesia. The patients affected were younger (p < 0.05) and the site of the dural puncture was higher (p < 0.01) than those individuals without pain. Five of the 13 patients (38%) with pain and seven of the 41 patients (17%) without pain admitted to a high alcohol intake, which might be a contributing factor. Leg and/or back pain is associated with the intrathecal use of hyperbaric 5% lignocaine.
8686832	0	17	Leg and back pain	Disease	D001416
8686832	67	77	lignocaine	Chemical	D008012
8686832	133	143	lignocaine	Chemical	D008012
8686832	155	162	glucose	Chemical	D005947
8686832	248	276	pain in the legs and/or back	Disease	D001416
8686832	444	448	pain	Disease	D010146
8686832	485	489	pain	Disease	D010146
8686832	533	537	pain	Disease	D010146
8686832	557	564	alcohol	Chemical	D000431
8686832	611	631	Leg and/or back pain	Disease	D001416
8686832	688	698	lignocaine	Chemical	D008012
8686832	CID	D008012	D001416

8607407|t|Acute blood pressure elevations with caffeine in men with borderline systemic hypertension.
8607407|a|Whether the vasoconstrictive actions of caffeine are enhanced in hypertensive persons has not been demonstrated. Thus, caffeine (3.3 mg/kg) versus placebo was tested in 48 healthy men (aged 20 to 35 years) selected after screening on 2 separate occasions. Borderline hypertensive men (n = 24) were selected with screening systolic blood pressure (BP) of 140 to 160 mm Hg and/or diastolic BP 90 to 99 mm Hg. Low-risk controls (n = 24) reported no parental history of hypertension and had screening BP < 130/85 mm Hg. Participants were then tested on 2 occasions after 12-hour abstinence from caffeine in each of 2 protocols; this required a total of 4 laboratory visits. Caffeine-induced changes in diastolic BP were 2 to 3 times larger in borderline subjects than in controls (+8.4 vs +3.8 mm Hg, p < 0.0001), and were attributable to larger changes in impedance-derived measures of systemic vascular resistance (+135 vs +45 dynes.s.cm-5, p < 0.004). These findings were consistent and reached significance in both protocols. The percentage of borderline subjects in whom diastolic BP changes exceeded the median control response was 96%. Consequently, whereas all participants exhibited normotensive levels during the resting predrug baseline, 33% of borderline subjects achieved hypertensive BP levels after caffeine ingestion. Thus, in borderline hypertensive men, exaggerated responses to caffeine were: selective for diastolic BP, consistent with greater vasoconstriction, replicated in 2 protocols, and representative of nearly all borderline hypertensives. We suspect that the potential for caffeine to stabilize high resistance states in susceptible persons suggests that its use may facilitate their disease progression, as well as hinder accurate diagnosis and treatment.
8607407	37	45	caffeine	Chemical	D002110
8607407	78	90	hypertension	Disease	D006973
8607407	132	140	caffeine	Chemical	D002110
8607407	157	169	hypertensive	Disease	D006973
8607407	211	219	caffeine	Chemical	D002110
8607407	359	371	hypertensive	Disease	D006973
8607407	558	570	hypertension	Disease	D006973
8607407	683	691	caffeine	Chemical	D002110
8607407	762	770	Caffeine	Chemical	D002110
8607407	1373	1385	hypertensive	Disease	D006973
8607407	1402	1410	caffeine	Chemical	D002110
8607407	1442	1454	hypertensive	Disease	D006973
8607407	1485	1493	caffeine	Chemical	D002110
8607407	1641	1654	hypertensives	Disease	D006973
8607407	1690	1698	caffeine	Chemical	D002110
8607407	CID	D002110	D006973

8111719|t|Hallucinations and ifosfamide-induced neurotoxicity.
8111719|a|BACKGROUND: Hallucinations as a symptom of central neurotoxicity are a known but poorly described side effect of ifosfamide. Most cases of ifosfamide-induced hallucinations have been reported with other mental status changes. METHODS: The authors interviewed six persons with ifosfamide-induced hallucinations in the presence of a clear sensorium. All patients were receiving high-dose ifosfamide as part of their bone marrow transplant procedure. RESULTS: Hallucinations occurred only when the patient's eyes were closed and, in all but one case, were reported as disturbing or frightening. Underreporting of these hallucinations by patients is likely. CONCLUSIONS: Hallucinations may be the sole or first manifestation of neurotoxicity. The incidence may be dose and infusion-time related. The clinician should be alerted for possible ifosfamide-induced hallucinations, which may occur without other signs of neurotoxicity. "Eyes-closed" hallucinatory experiences appear to be an unusual feature of this presentation. Patients anxious about this experience respond well to support and education about this occurrence. Optimal pharmacologic management of disturbed patients is unclear. If agitation becomes marked, high-potency neuroleptics (i.e., haloperidol) may be effective.
8111719	0	14	Hallucinations	Disease	D006212
8111719	19	29	ifosfamide	Chemical	D007069
8111719	38	51	neurotoxicity	Disease	D020258
8111719	65	79	Hallucinations	Disease	D006212
8111719	104	117	neurotoxicity	Disease	D020258
8111719	166	176	ifosfamide	Chemical	D007069
8111719	192	202	ifosfamide	Chemical	D007069
8111719	211	225	hallucinations	Disease	D006212
8111719	329	339	ifosfamide	Chemical	D007069
8111719	348	362	hallucinations	Disease	D006212
8111719	439	449	ifosfamide	Chemical	D007069
8111719	510	524	Hallucinations	Disease	D006212
8111719	669	683	hallucinations	Disease	D006212
8111719	720	734	Hallucinations	Disease	D006212
8111719	777	790	neurotoxicity	Disease	D020258
8111719	890	900	ifosfamide	Chemical	D007069
8111719	909	923	hallucinations	Disease	D006212
8111719	964	977	neurotoxicity	Disease	D020258
8111719	993	1006	hallucinatory	Disease	D006212
8111719	1243	1252	agitation	Disease	D011595
8111719	1302	1313	haloperidol	Chemical	D006220
8111719	CID	D007069	D006212

7059267|t|Chlorpropamide-induced optic neuropathy.
7059267|a|A 65-year-old woman with adult-onset diabetes treated with chlorpropamide (Diabenese) had a toxic optic neuropathy that resolved with discontinuation of chlorpropamide therapy. Visual loss occurs in diabetics for a variety of reasons, and accurate diagnosis is necessary to institute appropriate therapy. The possibility of a drug-induced optic neuropathy should be considered in the differential diagnosis of visual loss in diabetics.
7059267	0	14	Chlorpropamide	Chemical	D002747
7059267	23	39	optic neuropathy	Disease	D009901
7059267	66	86	adult-onset diabetes	Disease	D003924
7059267	100	114	chlorpropamide	Chemical	D002747
7059267	116	125	Diabenese	Chemical	D002747
7059267	133	155	toxic optic neuropathy	Disease	D009901
7059267	194	208	chlorpropamide	Chemical	D002747
7059267	218	229	Visual loss	Disease	D014786
7059267	240	249	diabetics	Disease	D003920
7059267	380	396	optic neuropathy	Disease	D009901
7059267	451	462	visual loss	Disease	D014786
7059267	466	475	diabetics	Disease	D003920
7059267	CID	D002747	D009901

6381653|t|Levodopa-induced dyskinesia and thalamotomy.
6381653|a|Levodopa-induced dyskinesia of the limbs in thirteen cases of Parkinsonism, which was choreic, ballistic or dystonic in type, was alleviated almost completely by stereotaxic surgery using a microelectrode technique for the ventralis oralis anterior and posterior nuclei of the thalamus, but much less by the ventralis intermedius nucleus. Control of levodopa-induced dyskinesias by thalamic lesions in the course of routine treatment of Parkinsonism is discussed.
6381653	0	8	Levodopa	Chemical	D007980
6381653	17	27	dyskinesia	Disease	D004409
6381653	45	53	Levodopa	Chemical	D007980
6381653	62	72	dyskinesia	Disease	D004409
6381653	107	119	Parkinsonism	Disease	D010302
6381653	153	161	dystonic	Disease	D020821
6381653	395	403	levodopa	Chemical	D007980
6381653	412	423	dyskinesias	Disease	D004409
6381653	427	443	thalamic lesions	Disease	D013786
6381653	482	494	Parkinsonism	Disease	D010302
6381653	CID	D007980	D004409

3950060|t|Factors associated with nephrotoxicity and clinical outcome in patients receiving amikacin.
3950060|a|Data from 60 patients treated with amikacin were analyzed for factors associated with nephrotoxicity. In 42 of these patients, data were examined for factors associated with clinical outcome. Variables evaluated included patient weight, age, sex, serum creatinine level, creatinine clearance, duration of therapy, total dose, mean daily dose, organism minimum inhibitory concentration (MIC), mean peak levels, mean trough levels, mean area under the serum concentration-time curve (AUC), total AUC, mean AUC greater than MIC, total AUC greater than MIC, mean Schumacher's intensity factor (IF), total IF, In (mean maximum concentration [Cmax]/MIC). Model-dependent pharmacokinetic parameters were calculated by computer based on a one-compartment model. When the parameters were examined individually, duration of therapy and total AUC correlated significantly (P less than .05) with nephrotoxicity. In contrast, a stepwise discriminant function analysis identified only duration of therapy (P less than .001) as an important factor. Based on this model and on Bayes' theorem, the predictive accuracy of identifying "nephrotoxic" patients increased from 0.17 to 0.39. When examined individually, mean IF, MIC, total dose, mean daily dose, and ln (mean Cmax/MIC) correlated significantly (P less than .05) with cure. In contrast, a simultaneous multivariable analysis identified IF, MIC, and total dose according to one model and ln (mean Cmax/MIC) according to a second statistical model of parameters selected to have the greatest prospective value. Based on Bayes' theorem and the first model, the predictive accuracy of identifying patients not cured increased from 0.19 to 0.83. For the second model, the predictive accuracy increased from 0.19 to 0.50.(ABSTRACT TRUNCATED AT 250 WORDS)
3950060	24	38	nephrotoxicity	Disease	D007674
3950060	82	90	amikacin	Chemical	D000583
3950060	127	135	amikacin	Chemical	D000583
3950060	178	192	nephrotoxicity	Disease	D007674
3950060	345	355	creatinine	Chemical	D003404
3950060	363	373	creatinine	Chemical	D003404
3950060	976	990	nephrotoxicity	Disease	D007674
3950060	1209	1220	nephrotoxic	Disease	D007674
3950060	CID	D000583	D007674

3311455|t|Cardiac transplantation: improved quality of survival with a modified immunosuppressive protocol.
3311455|a|The effects on renal function on two different immunosuppressive protocols were evaluated retrospectively in two subsequent groups of heart transplant recipients. In group I, cyclosporine was given before the procedure at a loading dose of 17.5 mg/kg and then continued after the procedure to keep a whole blood level about 1000 ng/ml. In group II, cyclosporine was started only after the procedure at a lower dosage and was complemented by azathioprine, which was used for the first postoperative week. Group II showed a better perioperative renal function as determined by serum blood urea nitrogen and serum creatinine levels. Group II also showed a significant decrease of chronic nephrotoxicity secondary to long-term therapy with cyclosporine. Despite this improvement in late renal function, group II still shows a slow rise in serum creatinine. We think that even these lower dosages of cyclosporine can cause chronic nephrotoxicity and that further modification of the immunosuppressive regimen is required to completely abolish this toxic side effect.
3311455	273	285	cyclosporine	Chemical	D016572
3311455	447	459	cyclosporine	Chemical	D016572
3311455	539	551	azathioprine	Chemical	D001379
3311455	685	698	urea nitrogen	Chemical	D001806
3311455	709	719	creatinine	Chemical	D003404
3311455	783	797	nephrotoxicity	Disease	D007674
3311455	834	846	cyclosporine	Chemical	D016572
3311455	939	949	creatinine	Chemical	D003404
3311455	993	1005	cyclosporine	Chemical	D016572
3311455	1024	1038	nephrotoxicity	Disease	D007674
3311455	CID	D016572	D007674

2051906|t|Reversible cholestasis with bile duct injury following azathioprine therapy. A case report.
2051906|a|A 67-year-old patient, with primary polymyositis and without previous evidence of liver disease, developed clinical and biochemical features of severe cholestasis 3 months after initiation of azathioprine therapy. Liver biopsy showed cholestasis with both cytological and architectural alterations of interlobular bile ducts. Azathioprine withdrawal resulted after 7 weeks in the resolution of clinical and biochemical abnormalities. It is believed that this is the first reported case of reversible azathioprine-induced cholestasis associated with histological evidence of bile duct injury.
2051906	11	22	cholestasis	Disease	D002779
2051906	28	44	bile duct injury	Disease	D002779
2051906	55	67	azathioprine	Chemical	D001379
2051906	128	140	polymyositis	Disease	D017285
2051906	174	187	liver disease	Disease	D008107
2051906	243	254	cholestasis	Disease	D002779
2051906	284	296	azathioprine	Chemical	D001379
2051906	326	337	cholestasis	Disease	D002779
2051906	418	430	Azathioprine	Chemical	D001379
2051906	592	604	azathioprine	Chemical	D001379
2051906	613	624	cholestasis	Disease	D002779
2051906	666	682	bile duct injury	Disease	D002779
2051906	CID	D001379	D002779

2021202|t|Renal function and hemodynamics during prolonged isoflurane-induced hypotension in humans.
2021202|a|The effect of isoflurane-induced hypotension on glomerular function and renal blood flow was investigated in 20 human subjects. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by inulin and para-aminohippurate (PAH) clearance, respectively. Anesthesia was maintained with fentanyl, nitrous oxide, oxygen, and isoflurane. Hypotension was induced for 236.9 +/- 15.1 min by increasing the isoflurane inspired concentration to maintain a mean arterial pressure of 59.8 +/- 0.4 mmHg. GFR and ERPF decreased with the induction of anesthesia but not significantly more during hypotension. Postoperatively, ERPF returned to preoperative values, whereas GFR was higher than preoperative values. Renal vascular resistance increased during anesthesia but decreased when hypotension was induced, allowing the maintenance of renal blood flow. We conclude that renal compensatory mechanisms are preserved during isoflurane-induced hypotension and that renal function and hemodynamics quickly return to normal when normotension is resumed.
2021202	49	59	isoflurane	Chemical	D007530
2021202	68	79	hypotension	Disease	D007022
2021202	105	115	isoflurane	Chemical	D007530
2021202	124	135	hypotension	Disease	D007022
2021202	319	338	para-aminohippurate	Chemical	D010130
2021202	340	343	PAH	Chemical	D010130
2021202	401	409	fentanyl	Chemical	D005283
2021202	411	424	nitrous oxide	Chemical	D009609
2021202	426	432	oxygen	Chemical	D010100
2021202	438	448	isoflurane	Chemical	D007530
2021202	450	461	Hypotension	Disease	D007022
2021202	515	525	isoflurane	Chemical	D007530
2021202	698	709	hypotension	Disease	D007022
2021202	888	899	hypotension	Disease	D007022
2021202	1027	1037	isoflurane	Chemical	D007530
2021202	1046	1057	hypotension	Disease	D007022
2021202	CID	D007530	D007022

1848636|t|Debrisoquine phenotype and the pharmacokinetics and beta-2 receptor pharmacodynamics of metoprolol and its enantiomers.
1848636|a|The metabolism of the cardioselective beta-blocker metoprolol is under genetic control of the debrisoquine/sparteine type. The two metabolic phenotypes, extensive (EM) and poor metabolizers (PM), show different stereoselective metabolism, resulting in apparently higher beta-1 adrenoceptor antagonistic potency of racemic metoprolol in EMs. We investigated if the latter also applies to the beta-2 adrenoceptor antagonism by metoprolol. The drug effect studied was the antagonism by metoprolol of terbutaline-induced hypokalemia. By using pharmacokinetic pharmacodynamic modeling the pharmacodynamics of racemic metoprolol and the active S-isomer, were quantitated in EMs and PMs in terms of IC50 values, representing metoprolol plasma concentrations resulting in half-maximum receptor occupancy. Six EMs received 0.5 mg of terbutaline s.c. on two different occasions: 1) 1 hr after administration of a placebo and 2) 1 hr after 150 mg of metoprolol p.o. Five PMs were studied according to the same protocol, except for a higher terbutaline dose (0.75 mg) on day 2. Blood samples for the analysis of plasma potassium, terbutaline, metoprolol (racemic, R- and S-isomer), and alpha-hydroxymetoprolol concentrations were taken at regular time intervals, during 8 hr after metoprolol. In PMs, metoprolol increased the terbutaline area under the plasma concentration vs. time curve (+67%). Higher metoprolol/alpha-hydroxymetoprolol ratios in PMs were predictive for higher R-/S-isomer ratios of unchanged drug. There was a difference in metoprolol potency with higher racemic metoprolol IC50 values in PMs (72 +/- 7 ng.ml-1) than EMs (42 +/- 8 ng.ml-1, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)
1848636	0	12	Debrisoquine	Chemical	D003647
1848636	88	98	metoprolol	Chemical	D008790
1848636	171	181	metoprolol	Chemical	D008790
1848636	214	226	debrisoquine	Chemical	D003647
1848636	227	236	sparteine	Chemical	D013034
1848636	442	452	metoprolol	Chemical	D008790
1848636	545	555	metoprolol	Chemical	D008790
1848636	603	613	metoprolol	Chemical	D008790
1848636	617	628	terbutaline	Chemical	D013726
1848636	637	648	hypokalemia	Disease	D007008
1848636	732	742	metoprolol	Chemical	D008790
1848636	838	848	metoprolol	Chemical	D008790
1848636	944	955	terbutaline	Chemical	D013726
1848636	1059	1069	metoprolol	Chemical	D008790
1848636	1149	1160	terbutaline	Chemical	D013726
1848636	1227	1236	potassium	Chemical	D011188
1848636	1238	1249	terbutaline	Chemical	D013726
1848636	1251	1261	metoprolol	Chemical	D008790
1848636	1294	1317	alpha-hydroxymetoprolol	Chemical	C029504
1848636	1389	1399	metoprolol	Chemical	D008790
1848636	1409	1419	metoprolol	Chemical	D008790
1848636	1434	1445	terbutaline	Chemical	D013726
1848636	1512	1522	metoprolol	Chemical	D008790
1848636	1523	1546	alpha-hydroxymetoprolol	Chemical	C029504
1848636	1652	1662	metoprolol	Chemical	D008790
1848636	1691	1701	metoprolol	Chemical	D008790
1848636	CID	D013726	D007008

1445986|t|Cefotetan-induced immune hemolytic anemia.
1445986|a|Immune hemolytic anemia due to a drug-adsorption mechanism has been described primarily in patients receiving penicillins and first-generation cephalosporins. We describe a patient who developed anemia while receiving intravenous cefotetan. Cefotetan-dependent antibodies were detected in the patient's serum and in an eluate prepared from his red blood cells. The eluate also reacted weakly with red blood cells in the absence of cefotetan, suggesting the concomitant formation of warm-reactive autoantibodies. These observations, in conjunction with clinical and laboratory evidence of extravascular hemolysis, are consistent with drug-induced hemolytic anemia, possibly involving both drug-adsorption and autoantibody formation mechanisms. This case emphasizes the need for increased awareness of hemolytic reactions to all cephalosporins.
1445986	0	9	Cefotetan	Chemical	D015313
1445986	25	41	hemolytic anemia	Disease	D000743
1445986	50	66	hemolytic anemia	Disease	D000743
1445986	153	164	penicillins	Chemical	D010406
1445986	186	200	cephalosporins	Chemical	D002511
1445986	238	244	anemia	Disease	D000740
1445986	273	282	cefotetan	Chemical	D015313
1445986	284	293	Cefotetan	Chemical	D015313
1445986	474	483	cefotetan	Chemical	D015313
1445986	645	654	hemolysis	Disease	D006461
1445986	689	705	hemolytic anemia	Disease	D000743
1445986	870	884	cephalosporins	Chemical	D002511
1445986	CID	D015313	D000743

982002|t|Acute renal failure subsequent to the administration of rifampicin. A follow-up study of cases reported earlier.
982002|a|A clinical presentation is made of a 2-3 year follow-up of six cases of acute renal failure that have been reported earlier. The patients had developed transient renal failure after the intermittent administration of rifampicin. The stage of olig-anuria lasted for 1-3 weeks, and five of the patients were treated by hemodialysis. Two of the patients died due to unrelated causes during the follow-up period. The four patients re-examined were clinically cured. Pathologic findings by light microscopy and immunofluorescence at biopsy were scarce. Nothing abnormal was seen by electron microscopy in two of the cases studied. Renal function was normal. In three cases the excretion at 131I-hippuran renography was slightly slowed. Although in the acute stage the renal lesions histologically appeared toxic, evidence suggestive of an immunological mechanism cannot be excluded.
982002	0	19	Acute renal failure	Disease	D058186
982002	56	66	rifampicin	Chemical	D012293
982002	185	204	acute renal failure	Disease	D058186
982002	275	288	renal failure	Disease	D051437
982002	330	340	rifampicin	Chemical	D012293
982002	360	366	anuria	Disease	D001002
982002	876	889	renal lesions	Disease	D007674
982002	CID	D012293	D058186

343678|t|Type B hepatitis after needle-stick exposure: prevention with hepatitis B immune globulin. Final report of the Veterans Administration Cooperative Study.
343678|a|Hepatitis B immune globulin (HBIG) and immune serum globulin (ISG) were examined in a randomized, double-blind trial to assess their relative efficacies in preventing type B hepatitis after needle-stick exposure to hepatitis B surface antigen (HBsAG)-positive donors. Clinical hepatitis developed in 1.4% of HBIG and in 5.9% of ISG recipients (P = 0.016), and seroconversion (anti-HBs) occurred in 5.6% and 20.7% of them respectively (P less than 0.001). Mild and transient side-effects were noted in 3.0% of ISG and in 3.2% of HBIG recipients. Available donor sera were examined for DNA polymerase (DNAP) and e antigen and antibody (HBeAg; anti-HBE). Both DNAP and HBeAg showed a highly statistically significant correlation with the infectivity of HBsAg-positive donors. Hepatitis B immune globulin remained significantly superior to ISG in preventing type B hepatitis even when the analysis was confined to these two high-risk subgroups. The efficacy of ISG in preventing type B hepatitis cannot be ascertained because a true placebo group was not included.
343678	0	16	Type B hepatitis	Disease	D006509
343678	62	73	hepatitis B	Disease	D006509
343678	154	165	Hepatitis B	Disease	D006509
343678	321	337	type B hepatitis	Disease	D006509
343678	369	396	hepatitis B surface antigen	Chemical	D006514
343678	398	403	HBsAG	Chemical	D006514
343678	431	440	hepatitis	Disease	D056486
343678	788	793	HBeAg	Chemical	D006513
343678	820	825	HBeAg	Chemical	D006513
343678	904	909	HBsAg	Chemical	D006514
343678	927	938	Hepatitis B	Disease	D006509
343678	1008	1024	type B hepatitis	Disease	D006509
343678	1129	1145	type B hepatitis	Disease	D006509
343678	CID	D006513	D006509

8888541|t|Serotonin syndrome from venlafaxine-tranylcypromine interaction.
8888541|a|Excessive stimulation of serotonin 5HT1A receptors causes a syndrome of serotonin excess that consists of shivering, muscle rigidity, salivation, confusion, agitation and hyperthermia. The most common cause of this syndrome is an interaction between a monoamine oxidase inhibitor (MAOI) and a specific serotonin reuptake inhibitor. Venlafaxine is a new antidepressant agent that inhibits the reuptake of serotonin and norepinephrine. We report a venlafaxine-MAOI interaction that resulted in the serotonin syndrome in a 23-y-old male who was taking tranylcypromine for depression. He had been well until the morning of presentation when he took 1/2 tab of venlafaxine. Within 2 h he became confused with jerking movements of his extremities, tremors and rigidity. He was brought directly to a hospital where he was found to be agitated and confused with shivering, myoclonic jerks, rigidity, salivation and diaphoresis. His pupils were 7 mm and sluggishly reactive to light. Vital signs were: blood pressure 120/67 mm Hg, heart rate 127/min, respiratory rate 28/min, and temperature 97 F. After 180 mg of diazepam i.v. he remained tremulous with muscle rigidity and clenched jaws. He was intubated for airway protection and because of hypoventilation, and was paralyzed to control muscle rigidity. His subsequent course was remarkable for non-immune thrombocytopenia which resolved. The patient's maximal temperature was 101.2 F and his CPK remained < 500 units/L with no other evidence of rhabdomyolysis. His mental status normalized and he was transferred to a psychiatry ward. This patient survived without sequelae due to the aggressive sedation and neuromuscular paralysis.
8888541	0	18	Serotonin syndrome	Disease	D020230
8888541	24	35	venlafaxine	Chemical	C047426
8888541	36	51	tranylcypromine	Chemical	D014191
8888541	90	99	serotonin	Chemical	D012701
8888541	137	146	serotonin	Chemical	D012701
8888541	182	197	muscle rigidity	Disease	D009127
8888541	199	209	salivation	Disease	D012798
8888541	211	220	confusion	Disease	D003221
8888541	222	231	agitation	Disease	D011595
8888541	236	248	hyperthermia	Disease	D005334
8888541	367	376	serotonin	Chemical	D012701
8888541	397	408	Venlafaxine	Chemical	C047426
8888541	469	478	serotonin	Chemical	D012701
8888541	483	497	norepinephrine	Chemical	D009638
8888541	511	522	venlafaxine	Chemical	C047426
8888541	561	579	serotonin syndrome	Disease	D020230
8888541	614	629	tranylcypromine	Chemical	D014191
8888541	634	644	depression	Disease	D003866
8888541	721	732	venlafaxine	Chemical	C047426
8888541	807	814	tremors	Disease	D014202
8888541	819	827	rigidity	Disease	D009127
8888541	930	945	myoclonic jerks	Disease	D009207
8888541	947	955	rigidity	Disease	D009127
8888541	957	967	salivation	Disease	D012798
8888541	1170	1178	diazepam	Chemical	D003975
8888541	1211	1226	muscle rigidity	Disease	D009127
8888541	1300	1315	hypoventilation	Disease	D007040
8888541	1325	1334	paralyzed	Disease	D010243
8888541	1346	1361	muscle rigidity	Disease	D009127
8888541	1415	1431	thrombocytopenia	Disease	D013921
8888541	1555	1569	rhabdomyolysis	Disease	D012206
8888541	1733	1742	paralysis	Disease	D010243
8888541	CID	C047426	D005334
8888541	CID	C047426	D013921
8888541	CID	C047426	D020230
8888541	CID	D014191	D005334
8888541	CID	D014191	D009207
8888541	CID	C047426	D009127
8888541	CID	C047426	D009207
8888541	CID	C047426	D003221
8888541	CID	C047426	D014202
8888541	CID	D014191	D014202
8888541	CID	D014191	D020230
8888541	CID	C047426	D012798
8888541	CID	D014191	D003221
8888541	CID	D014191	D013921
8888541	CID	D014191	D012798
8888541	CID	D014191	D009127

8106150|t|Effect of nondopaminergic drugs on L-dopa-induced dyskinesias in MPTP-treated monkeys.
8106150|a|A group of four monkeys was rendered parkinsonian with the toxin MPTP. They were then treated chronically with L-DOPA/benserazide 50/12.5 mg/kg given orally daily for 2 months. This dose produced a striking antiparkinsonian effect, but all animals manifested dyskinesia. A series of agents acting primarily on neurotransmitters other than dopamine were then tested in combination with L-DOPA to see if the dyskinetic movements would be modified. Several drugs, including clonidine, physostigmine, methysergide, 5-MDOT, propranolol, and MK-801, markedly reduced the dyskinetic movements but at the cost of a return of parkinsonian symptomatology. However, yohimbine and meperidine reduced predominantly the dyskinetic movements. Baclofen was also useful in one monkey against a more dystonic form of dyskinesia. Atropine converted the dystonic movements into chorea.
8106150	35	41	L-dopa	Chemical	D007980
8106150	50	61	dyskinesias	Disease	D004409
8106150	65	69	MPTP	Chemical	D015632
8106150	124	136	parkinsonian	Disease	D020734
8106150	152	156	MPTP	Chemical	D015632
8106150	198	216	L-DOPA/benserazide	Chemical	C005177
8106150	346	356	dyskinesia	Disease	D004409
8106150	426	434	dopamine	Chemical	D004298
8106150	472	478	L-DOPA	Chemical	D007980
8106150	493	503	dyskinetic	Disease	D004409
8106150	558	567	clonidine	Chemical	D003000
8106150	569	582	physostigmine	Chemical	D010830
8106150	584	596	methysergide	Chemical	D008784
8106150	598	604	5-MDOT	Chemical	-1
8106150	606	617	propranolol	Chemical	D011433
8106150	623	629	MK-801	Chemical	D016291
8106150	652	662	dyskinetic	Disease	D004409
8106150	704	716	parkinsonian	Disease	D020734
8106150	742	751	yohimbine	Chemical	D015016
8106150	756	766	meperidine	Chemical	D008614
8106150	793	803	dyskinetic	Disease	D004409
8106150	815	823	Baclofen	Chemical	D001418
8106150	869	877	dystonic	Disease	D020821
8106150	886	896	dyskinesia	Disease	D004409
8106150	898	906	Atropine	Chemical	D001285
8106150	921	929	dystonic	Disease	D020821
8106150	945	951	chorea	Disease	D002819
8106150	CID	C005177	D004409
8106150	CID	D015632	D020734

21418164|t|CCNU (lomustine) toxicity in dogs: a retrospective study (2002-07).
21418164|a|OBJECTIVE: To describe the incidence of haematological, renal, hepatic and gastrointestinal toxicities in tumour-bearing dogs receiving 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). DESIGN: The medical records of 206 dogs that were treated with CCNU at the Melbourne Veterinary Specialist Centre between February 2002 and December 2007 were retrospectively evaluated. RESULTS: Of the 206 dogs treated with CCNU, 185 met the inclusion criteria for at least one class of toxicity. CCNU was used most commonly in the treatment of lymphoma, mast cell tumour, brain tumour, histiocytic tumours and epitheliotropic lymphoma. Throughout treatment, 56.9% of dogs experienced neutropenia, 34.2% experienced anaemia and 14.2% experienced thrombocytopenia. Gastrointestinal toxicosis was detected in 37.8% of dogs, the most common sign of which was vomiting (24.3%). Potential renal toxicity and elevated alanine transaminase (ALT) concentration were reported in 12.2% and 48.8% of dogs, respectively. The incidence of hepatic failure was 1.2%. CONCLUSIONS: CCNU-associated toxicity in dogs is common, but is usually not life threatening.
21418164	0	4	CCNU	Chemical	D008130
21418164	6	15	lomustine	Chemical	D008130
21418164	17	25	toxicity	Disease	D064420
21418164	108	170	haematological, renal, hepatic and gastrointestinal toxicities	Disease	D006402|D007674|D056486|D005767	haematological toxicities|renal toxicities|hepatic toxicities|gastrointestinal toxicities
21418164	204	248	1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea	Chemical	D008130
21418164	250	254	CCNU	Chemical	D008130
21418164	320	324	CCNU	Chemical	D008130
21418164	481	485	CCNU	Chemical	D008130
21418164	544	552	toxicity	Disease	D064420
21418164	554	558	CCNU	Chemical	D008130
21418164	602	610	lymphoma	Disease	D008223
21418164	612	628	mast cell tumour	Disease	D034801
21418164	630	642	brain tumour	Disease	D001932
21418164	644	663	histiocytic tumours	Disease	D015620
21418164	668	692	epitheliotropic lymphoma	Disease	D008223
21418164	742	753	neutropenia	Disease	D009503
21418164	773	780	anaemia	Disease	D000740
21418164	803	819	thrombocytopenia	Disease	D013921
21418164	821	847	Gastrointestinal toxicosis	Disease	D005767
21418164	913	921	vomiting	Disease	D014839
21418164	947	955	toxicity	Disease	D064420
21418164	969	976	alanine	Chemical	D000409
21418164	1083	1098	hepatic failure	Disease	D017093
21418164	1122	1126	CCNU	Chemical	D008130
21418164	1138	1146	toxicity	Disease	D064420
21418164	CID	D008130	D005767
21418164	CID	D008130	D017093
21418164	CID	D008130	D013921
21418164	CID	D008130	D007674
21418164	CID	D008130	D000740
21418164	CID	D008130	D009503
21418164	CID	D008130	D014839

9121607|t|Neuroactive steroids protect against pilocarpine- and kainic acid-induced limbic seizures and status epilepticus in mice.
9121607|a|Several structurally related metabolites of progesterone (3 alpha-hydroxy pregnane-20-ones) and deoxycorticosterone (3 alpha-hydroxy pregnane-21-diol-20-ones) and their 3 beta-epimers were evaluated for protective activity against pilocarpine-, kainic acid- and N-methyl-D-aspartate (NMDA)-induced seizures in mice. Steroids with the 3-hydroxy group in the alpha-position and 5-H in the alpha- or beta-configurations were highly effective in protecting against pilocarpine (416 mg/kg, s.c.)-induced limbic motor seizures and status epilepticus (ED50 values, 7.0-18.7 mg/kg, i.p.). The corresponding epimers with the 3-hydroxy group in the beta-position were also effective but less potent (ED50 values, 33.8-63.5, i.p.). Although the neuroactive steroids were considerably less potent than the benzodiazepine clonazepam in protecting against pilocarpine seizures, steroids with the 5 alpha,3 alpha-configuration had comparable or higher protective index values (TD50 for motor impairment divided by ED50 for seizure protection) than clonazepam, indicating that some neuroactive steroids may have lower relative toxicity. Steroids with the 5 alpha,3 alpha- or 5 beta,3 alpha-configurations also produced a dose-dependent delay in the onset of limbic seizures induced by kainic acid (32 mg/kg, s.c.), but did not completely protect against the seizures. However, when a second dose of the steroid was administered 1 hr after the first dose, complete protection from the kainic acid-induced limbic seizures and status epilepticus was obtained. The steroids also caused a dose-dependent delay in NMDA (257 mg/kg, s.c.)-induced lethality, but did not completely protect against NMDA seizures or lethality. We conclude that neuroactive steroids are highly effective in protecting against pilocarpine- and kainic acid-induced seizures and status epilepticus in mice, and may be of utility in the treatment of some forms of status epilepticus in humans.
9121607	12	20	steroids	Chemical	D013256
9121607	37	48	pilocarpine	Chemical	D010862
9121607	54	65	kainic acid	Chemical	D007608
9121607	81	89	seizures	Disease	D012640
9121607	94	112	status epilepticus	Disease	D013226
9121607	166	178	progesterone	Chemical	D011374
9121607	180	212	3 alpha-hydroxy pregnane-20-ones	Chemical	D011374
9121607	218	237	deoxycorticosterone	Chemical	D003900
9121607	239	279	3 alpha-hydroxy pregnane-21-diol-20-ones	Chemical	D003900
9121607	353	364	pilocarpine	Chemical	D010862
9121607	367	378	kainic acid	Chemical	D007608
9121607	384	404	N-methyl-D-aspartate	Chemical	D016202
9121607	406	410	NMDA	Chemical	D016202
9121607	420	428	seizures	Disease	D012640
9121607	438	446	Steroids	Chemical	D013256
9121607	583	594	pilocarpine	Chemical	D010862
9121607	634	642	seizures	Disease	D012640
9121607	647	665	status epilepticus	Disease	D013226
9121607	868	876	steroids	Chemical	D013256
9121607	916	930	benzodiazepine	Chemical	D001569
9121607	931	941	clonazepam	Chemical	D002998
9121607	964	975	pilocarpine	Chemical	D010862
9121607	976	984	seizures	Disease	D012640
9121607	986	994	steroids	Chemical	D013256
9121607	1130	1137	seizure	Disease	D012640
9121607	1155	1165	clonazepam	Chemical	D002998
9121607	1200	1208	steroids	Chemical	D013256
9121607	1233	1241	toxicity	Disease	D064420
9121607	1243	1251	Steroids	Chemical	D013256
9121607	1371	1379	seizures	Disease	D012640
9121607	1391	1402	kainic acid	Chemical	D007608
9121607	1464	1472	seizures	Disease	D012640
9121607	1509	1516	steroid	Chemical	D013256
9121607	1590	1601	kainic acid	Chemical	D007608
9121607	1617	1625	seizures	Disease	D012640
9121607	1630	1648	status epilepticus	Disease	D013226
9121607	1667	1675	steroids	Chemical	D013256
9121607	1714	1718	NMDA	Chemical	D016202
9121607	1795	1799	NMDA	Chemical	D016202
9121607	1800	1808	seizures	Disease	D012640
9121607	1852	1860	steroids	Chemical	D013256
9121607	1904	1915	pilocarpine	Chemical	D010862
9121607	1921	1932	kainic acid	Chemical	D007608
9121607	1941	1949	seizures	Disease	D012640
9121607	1954	1972	status epilepticus	Disease	D013226
9121607	2038	2056	status epilepticus	Disease	D013226
9121607	CID	D010862	D013226
9121607	CID	D007608	D013226
9121607	CID	D010862	D012640
9121607	CID	D007608	D012640

7905523|t|The safety and efficacy of combination N-butyl-deoxynojirimycin (SC-48334) and zidovudine in patients with HIV-1 infection and 200-500 CD4 cells/mm3.
7905523|a|We conducted a double-blind, randomized phase II study to evaluate the safety and activity of combination therapy with N-butyl-deoxynojirimycin (SC-48334) (an alpha-glucosidase I inhibitor) and zidovudine versus zidovudine alone. Patients with 200 to 500 CD4 cells/mm3 who tolerated < or = 12 weeks of prior zidovudine therapy received SC-48334 (1000 mg every 8 h) and zidovudine (100 mg every 8 h) or zidovudine and placebo. Sixty patients received combination therapy and 58, zidovudine and placebo. Twenty-three patients (38%) and 15 (26%), in the combination and zidovudine groups, respectively, discontinued therapy (p = 0.15). The mean SC-48334 steady-state trough level (4.04 +/- 0.99 micrograms/ml) was below the in vitro inhibitory concentration for human immunodeficiency virus (HIV). The mean increase in CD4 cells at week 4 was 73.8 cells/mm3 and 52.4 cells/mm3 for the combination and zidovudine groups, respectively (p > 0.36). For patients with prior zidovudine therapy, the mean change in CD4 cells in the combination and zidovudine groups was 63.7 cells/mm3 and 4.9 cells/mm3 at week 8 and 6.8 cells/mm3 and -45.1 cells/mm3 at week 16, respectively. The number of patients with suppression of HIV p24 antigenemia in the combination and zidovudine groups was six (40%) and two (11%) at week 4 (p = 0.10) and five (45%) and two (14%) at week 24 (p = 0.08), respectively. Diarrhea, flatulence, abdominal pain, and weight loss were common for combination recipients.(ABSTRACT TRUNCATED AT 250 WORDS)
7905523	39	63	N-butyl-deoxynojirimycin	Chemical	C059896
7905523	65	73	SC-48334	Chemical	C059896
7905523	79	89	zidovudine	Chemical	D015215
7905523	107	122	HIV-1 infection	Disease	D015658
7905523	269	293	N-butyl-deoxynojirimycin	Chemical	C059896
7905523	295	303	SC-48334	Chemical	C059896
7905523	344	354	zidovudine	Chemical	D015215
7905523	362	372	zidovudine	Chemical	D015215
7905523	458	468	zidovudine	Chemical	D015215
7905523	486	494	SC-48334	Chemical	C059896
7905523	519	529	zidovudine	Chemical	D015215
7905523	552	562	zidovudine	Chemical	D015215
7905523	628	638	zidovudine	Chemical	D015215
7905523	717	727	zidovudine	Chemical	D015215
7905523	792	800	SC-48334	Chemical	C059896
7905523	915	931	immunodeficiency	Disease	D007153
7905523	1048	1058	zidovudine	Chemical	D015215
7905523	1116	1126	zidovudine	Chemical	D015215
7905523	1188	1198	zidovudine	Chemical	D015215
7905523	1403	1413	zidovudine	Chemical	D015215
7905523	1536	1544	Diarrhea	Disease	D003967
7905523	1546	1556	flatulence	Disease	D005414
7905523	1558	1572	abdominal pain	Disease	D015746
7905523	1578	1589	weight loss	Disease	D015431
7905523	CID	C059896	D005414
7905523	CID	D015215	D015431
7905523	CID	D015215	D005414
7905523	CID	C059896	D015746
7905523	CID	C059896	D003967
7905523	CID	D015215	D015746
7905523	CID	D015215	D003967
7905523	CID	C059896	D015431

3431591|t|Recent preclinical and clinical studies with the thymidylate synthase inhibitor N10-propargyl-5,8-dideazafolic acid (CB 3717).
3431591|a|CB 3717, N10-propargyl-5,8-dideazafolic acid, is a tight-binding inhibitor of thymidylate synthase (TS) whose cytotoxicity is mediated solely through the inhibition of this enzyme. Recent preclinical studies have focused on the intracellular formation of CB 3717 polyglutamates. Following a 12-hour exposure of L1210 cells to 50 microM [3H]CB 3717, 30% of the extractable radioactivity could be accounted for as CB 3717 tetra- and pentaglutamate, as determined by high-pressure liquid chromatography (HPLC) analyses. As inhibitors of isolated L1210 TS, CB 3717 di-, tri-, tetra- and pentaglutamate are 26-, 87-, 119- and 114-fold more potent than CB 3717, respectively, and their formation may, therefore, be an important determinant of CB 3717 cytotoxicity. In early clinical studies with CB 3717, activity has been seen in breast cancer, ovarian cancer, hepatoma, and mesothelioma. Toxicities included hepatotoxicity, malaise, and dose-limiting nephrotoxicity. This latter effect is thought to be due to drug precipitation within the renal tubule as a result of the poor solubility of CB 3717 under acidic conditions. In an attempt to overcome this problem, a clinical trial of CB 3717 administered with alkaline diuresis is under way. Preliminary results at 400 and 500 mg/m2 suggest that a reduction in nephrotoxicity may have been achieved with only 1 instance of renal toxicity in 10 patients. Hepatotoxicity and malaise are again the most frequent side effects. Evidence of antitumor activity has been seen in 3 patients. Pharmacokinetic investigations have shown that alkaline diuresis does not alter CB 3717 plasma levels or urinary excretion and that satisfactory urinary alkalinization can be readily achieved.
3431591	80	115	N10-propargyl-5,8-dideazafolic acid	Chemical	C031662
3431591	117	124	CB 3717	Chemical	C031662
3431591	127	134	CB 3717	Chemical	C031662
3431591	136	171	N10-propargyl-5,8-dideazafolic acid	Chemical	C031662
3431591	237	249	cytotoxicity	Disease	D064420
3431591	382	389	CB 3717	Chemical	C031662
3431591	467	474	CB 3717	Chemical	C031662
3431591	539	546	CB 3717	Chemical	C031662
3431591	774	781	CB 3717	Chemical	C031662
3431591	864	871	CB 3717	Chemical	C031662
3431591	872	884	cytotoxicity	Disease	D064420
3431591	917	924	CB 3717	Chemical	C031662
3431591	952	965	breast cancer	Disease	D001943
3431591	967	981	ovarian cancer	Disease	D010051
3431591	983	991	hepatoma	Disease	D006528
3431591	997	1009	mesothelioma	Disease	D008654
3431591	1011	1021	Toxicities	Disease	D064420
3431591	1031	1045	hepatotoxicity	Disease	D056486
3431591	1047	1054	malaise	Disease	D005221
3431591	1074	1088	nephrotoxicity	Disease	D007674
3431591	1214	1221	CB 3717	Chemical	C031662
3431591	1307	1314	CB 3717	Chemical	C031662
3431591	1434	1448	nephrotoxicity	Disease	D007674
3431591	1496	1510	renal toxicity	Disease	D007674
3431591	1527	1541	Hepatotoxicity	Disease	D056486
3431591	1546	1553	malaise	Disease	D005221
3431591	1736	1743	CB 3717	Chemical	C031662
3431591	CID	C031662	D056486
3431591	CID	C031662	D007674
3431591	CID	C031662	D005221

33969|t|Ethopropazine and benztropine in neuroleptic-induced parkinsonism.
33969|a|In a 12-week controlled study ethopropazine was compared to benztropine in the treatment of parkinsonism induced by fluphenazine enanthate in 60 schizophrenic outpatients. Ethopropazine and benztropine were found to be equally effective in controlling parkinsonian symptoms and were as efficacious as procyclidine, their previous antiparkinsonian drug. However, benztropine treated patients had a significant increase in tardive dyskinesia compared to their condition during procyclindine treatment, and significantly more anxiety and depression than ethopropazine treated patients. This suggests that benztropine is not the anticholinergic drug of choice in the treatment of neuroleptic-induced parkinsonian symptoms, because of its more toxic central and peripheral atropinic effect.
33969	0	13	Ethopropazine	Chemical	C084820
33969	18	29	benztropine	Chemical	D001590
33969	53	65	parkinsonism	Disease	D010302
33969	97	110	ethopropazine	Chemical	C084820
33969	127	138	benztropine	Chemical	D001590
33969	159	171	parkinsonism	Disease	D010302
33969	183	205	fluphenazine enanthate	Chemical	C017610
33969	212	225	schizophrenic	Disease	D012559
33969	239	252	Ethopropazine	Chemical	C084820
33969	257	268	benztropine	Chemical	D001590
33969	319	340	parkinsonian symptoms	Disease	D010302
33969	368	380	procyclidine	Chemical	D011352
33969	429	440	benztropine	Chemical	D001590
33969	488	506	tardive dyskinesia	Disease	D004409
33969	542	555	procyclindine	Chemical	D011352
33969	590	597	anxiety	Disease	D001008
33969	602	612	depression	Disease	D003866
33969	618	631	ethopropazine	Chemical	C084820
33969	669	680	benztropine	Chemical	D001590
33969	763	784	parkinsonian symptoms	Disease	D010302
33969	CID	D001590	D001008
33969	CID	D001590	D003866
33969	CID	D001590	D004409
33969	CID	C017610	D010302

16844102|t|Effect of alpha-tocopherol and deferoxamine on methamphetamine-induced neurotoxicity.
16844102|a|Methamphetamine (MA)-induced dopaminergic neurotoxicity is believed to be associated with the increased formation of free radicals. This study examined the effect of alpha-tocopherol (alpha-TC), a scavenger of reactive oxygen species, and deferoxamine (DFO), an iron chelator, on the MA-induced neurotoxicity. Male rats were treated with MA (10 mg/kg, every 2 h for four injections). The rat received either alpha-TC (20 mg/kg) intraperitoneally for 3 days and 30 min prior to MA administration or DFO (50 mg/kg) subcutaneously 30 min before MA administration. The concentrations of dopamine (DA), serotonin and their metabolites decreased significantly after MA administration, which was inhibited by the alpha-TC and DFO pretreatment. alpha-TC and DFO attenuated the MA-induced hyperthermia as well as the alterations in the locomotor activity. The level of lipid peroxidation was higher and the reduced glutathione concentration was lower in the MA-treated rats. These changes were significantly attenuated by alpha-TC and DFO. This suggests that alpha-TC and DFO ameliorate the MA-induced neuronal damage by decreasing the level of oxidative stress.
16844102	10	26	alpha-tocopherol	Chemical	D024502
16844102	31	43	deferoxamine	Chemical	D003676
16844102	47	62	methamphetamine	Chemical	D008694
16844102	71	84	neurotoxicity	Disease	D020258
16844102	86	101	Methamphetamine	Chemical	D008694
16844102	103	105	MA	Chemical	D008694
16844102	128	141	neurotoxicity	Disease	D020258
16844102	252	268	alpha-tocopherol	Chemical	D024502
16844102	270	278	alpha-TC	Chemical	D024502
16844102	305	311	oxygen	Chemical	D010100
16844102	325	337	deferoxamine	Chemical	D003676
16844102	339	342	DFO	Chemical	D003676
16844102	348	352	iron	Chemical	D007501
16844102	370	372	MA	Chemical	D008694
16844102	381	394	neurotoxicity	Disease	D020258
16844102	424	426	MA	Chemical	D008694
16844102	494	502	alpha-TC	Chemical	D024502
16844102	563	565	MA	Chemical	D008694
16844102	584	587	DFO	Chemical	D003676
16844102	628	630	MA	Chemical	D008694
16844102	669	677	dopamine	Chemical	D004298
16844102	679	681	DA	Chemical	D004298
16844102	684	693	serotonin	Chemical	D012701
16844102	746	748	MA	Chemical	D008694
16844102	792	800	alpha-TC	Chemical	D024502
16844102	805	808	DFO	Chemical	D003676
16844102	823	831	alpha-TC	Chemical	D024502
16844102	836	839	DFO	Chemical	D003676
16844102	855	857	MA	Chemical	D008694
16844102	866	878	hyperthermia	Disease	D005334
16844102	992	1003	glutathione	Chemical	D005978
16844102	1035	1037	MA	Chemical	D008694
16844102	1099	1107	alpha-TC	Chemical	D024502
16844102	1112	1115	DFO	Chemical	D003676
16844102	1136	1144	alpha-TC	Chemical	D024502
16844102	1149	1152	DFO	Chemical	D003676
16844102	1168	1170	MA	Chemical	D008694
16844102	1179	1194	neuronal damage	Disease	D009422
16844102	CID	D008694	D009422
16844102	CID	D008694	D005334

14633084|t|Use of dexamethasone with mesna for the prevention of ifosfamide-induced hemorrhagic cystitis.
14633084|a|AIM: Hemorrhagic cystitis (HC) is a limiting side-effect of chemotherapy with ifosfamide (IFS). In the study presented here, we investigated the use of dexamethasone in combination with mesna for the prevention of IFS-induced HC. METHODS: Male Wistar rats (150-200 g; 6 rats per group) were treated with saline or mesna 5 min (i.p.) before and 2 and 6 h after (v.o.) administration of IFS. One, two or three doses of mesna were replaced with dexamethasone alone or with dexamethasone plus mesna. Cystitis was evaluated 24 h after its induction by the changes in bladder wet weight and by macroscopic and microscopic analysis. RESULTS: The replacement of the last dose or the last two doses of mesna with dexamethasone reduced the increase in bladder wet weight induced by IFS by 84.79% and 89.13%, respectively. In addition, it almost abolished the macroscopic and microscopic alterations induced by IFS. Moreover, the addition of dexamethasone to the last two doses of mesna was more efficient than three doses of mesna alone when evaluated microscopically. CONCLUSION: Dexamethasone in combination with mesna was efficient in blocking IFS-induced HC. However, the replacement of last two doses of mesna with saline or all of the mesna doses with dexamethasone did not prevent HC.
14633084	7	20	dexamethasone	Chemical	D003907
14633084	26	31	mesna	Chemical	D015080
14633084	54	64	ifosfamide	Chemical	D007069
14633084	73	93	hemorrhagic cystitis	Disease	D006470|D003556	hemorrhagic|cystitis
14633084	100	120	Hemorrhagic cystitis	Disease	D006470|D003556	Hemorrhagic|cystitis
14633084	122	124	HC	Disease	D006470|D003556
14633084	173	183	ifosfamide	Chemical	D007069
14633084	185	188	IFS	Chemical	D007069
14633084	247	260	dexamethasone	Chemical	D003907
14633084	281	286	mesna	Chemical	D015080
14633084	309	312	IFS	Chemical	D007069
14633084	321	323	HC	Disease	D006470|D003556
14633084	409	414	mesna	Chemical	D015080
14633084	480	483	IFS	Chemical	D007069
14633084	512	517	mesna	Chemical	D015080
14633084	537	550	dexamethasone	Chemical	D003907
14633084	565	578	dexamethasone	Chemical	D003907
14633084	584	589	mesna	Chemical	D015080
14633084	591	599	Cystitis	Disease	D003556
14633084	788	793	mesna	Chemical	D015080
14633084	799	812	dexamethasone	Chemical	D003907
14633084	867	870	IFS	Chemical	D007069
14633084	995	998	IFS	Chemical	D007069
14633084	1026	1039	dexamethasone	Chemical	D003907
14633084	1065	1070	mesna	Chemical	D015080
14633084	1110	1115	mesna	Chemical	D015080
14633084	1166	1179	Dexamethasone	Chemical	D003907
14633084	1200	1205	mesna	Chemical	D015080
14633084	1232	1235	IFS	Chemical	D007069
14633084	1244	1246	HC	Disease	D006470|D003556
14633084	1294	1299	mesna	Chemical	D015080
14633084	1326	1331	mesna	Chemical	D015080
14633084	1343	1356	dexamethasone	Chemical	D003907
14633084	1373	1375	HC	Disease	D006470|D003556
14633084	CID	D007069	D006470
14633084	CID	D007069	D003556

11999899|t|Behavioral effects of MK-801 on reserpine-treated mice.
11999899|a|The effects of dizocilpine (MK-801), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, were studied on dopamine-related behaviors induced by reserpine treatments. This study focuses on behavioral syndromes that may used as models for Parkinson's disease, or tardive dyskinesia, and its response after glutamatergic blockage. Reserpine (1 mg/kg), administered once every other day for 4 days, produced increases in orofacial dyskinesia, tongue protrusion and vacuous chewing in mice, which are signs indicative of tardive dyskinesia. Reserpine also produced tremor and catalepsy, which are signs suggestive of Parkinson's disease. MK-801 (0.1 mg/kg), administered 30 min before the observation test, prevented the vacuous chewing movements, tongue protrusions and catalepsy induced by reserpine. However, MK-801 injection produced a significant increase of tremor in reserpine-treated mice. Reserpine (1 mg/kg), administered 90 min before the test and followed by apomophine injection (0.1 mg/kg) 5 min before the test, did not produce oral dyskinesia in mice. On the other hand, reserpine induced increases in tremor and catalepsy compared to control mice. MK-801 (0.1 mg/kg) administration attenuated the catalepsy and tremor induced by reserpine. Pretreatment with reserpine (1 mg/kg) 24 h before the observation test produced increases in vacuous chewing movements and tongue protrusion, as well as increases in tremor and catalepsy, whereas MK-801 (0.1 mg/kg) injection 90 min before the test reversed the effects of reserpine. These results show that reserpine produces different and abnormal movements, which are related to dose and schedule employed and can be considered as parkinsonian-like and tardive dsykinesia signs. The glutamatergic blockage produced by NMDA can restore these signs, such as vacuous chewing movements, tongue protrusions, catalepsy and tremor according to the employed model.
11999899	22	28	MK-801	Chemical	D016291
11999899	32	41	reserpine	Chemical	D012110
11999899	71	82	dizocilpine	Chemical	D016291
11999899	84	90	MK-801	Chemical	D016291
11999899	110	130	N-methyl-D-aspartate	Chemical	D016202
11999899	132	136	NMDA	Chemical	D016202
11999899	175	183	dopamine	Chemical	D004298
11999899	213	222	reserpine	Chemical	D012110
11999899	306	325	Parkinson's disease	Disease	D010300
11999899	330	348	tardive dyskinesia	Disease	D004409
11999899	397	406	Reserpine	Chemical	D012110
11999899	486	506	orofacial dyskinesia	Disease	D009069
11999899	585	603	tardive dyskinesia	Disease	D004409
11999899	605	614	Reserpine	Chemical	D012110
11999899	629	635	tremor	Disease	D014202
11999899	640	649	catalepsy	Disease	D002375
11999899	681	700	Parkinson's disease	Disease	D010300
11999899	702	708	MK-801	Chemical	D016291
11999899	835	844	catalepsy	Disease	D002375
11999899	856	865	reserpine	Chemical	D012110
11999899	876	882	MK-801	Chemical	D016291
11999899	928	934	tremor	Disease	D014202
11999899	938	947	reserpine	Chemical	D012110
11999899	962	971	Reserpine	Chemical	D012110
11999899	1035	1045	apomophine	Chemical	D001058
11999899	1107	1122	oral dyskinesia	Disease	D009069
11999899	1151	1160	reserpine	Chemical	D012110
11999899	1182	1188	tremor	Disease	D014202
11999899	1193	1202	catalepsy	Disease	D002375
11999899	1229	1235	MK-801	Chemical	D016291
11999899	1278	1287	catalepsy	Disease	D002375
11999899	1292	1298	tremor	Disease	D014202
11999899	1310	1319	reserpine	Chemical	D012110
11999899	1339	1348	reserpine	Chemical	D012110
11999899	1487	1493	tremor	Disease	D014202
11999899	1498	1507	catalepsy	Disease	D002375
11999899	1517	1523	MK-801	Chemical	D016291
11999899	1593	1602	reserpine	Chemical	D012110
11999899	1628	1637	reserpine	Chemical	D012110
11999899	1661	1679	abnormal movements	Disease	D004409
11999899	1754	1766	parkinsonian	Disease	D010300
11999899	1776	1794	tardive dsykinesia	Disease	D004409
11999899	1841	1845	NMDA	Chemical	D016202
11999899	1926	1935	catalepsy	Disease	D002375
11999899	1940	1946	tremor	Disease	D014202
11999899	CID	D012110	D014202
11999899	CID	D012110	D004409
11999899	CID	D012110	D002375

9431903|t|Effect of glyceryl trinitrate on the sphincter of Oddi spasm evoked by prostigmine-morphine administration.
9431903|a|OBJECTIVE: In this study the effect of glyceryl trinitrate on the prostigmine-morphine-induced sphincter of Oddi spasm was evaluated in nine female patients with sphincter of Oddi dyskinesia. METHOD: Sphincter of Oddi spasm was induced by prostigmine-morphine administration (0.5 mg prostigmine intramuscularly and 10 mg morphine subcutaneously) and visualized by quantitative hepatobiliary scintigraphy. The entire procedure was repeated during glyceryl trinitrate infusion (Nitrolingual 1 microg/kg/min for 120 min). RESULTS: Prostigmine-morphine provocation caused significant increases in the time to peak activity (Tmax) over the hepatic hilum (HH: 34.33 +/- 5.05 vs. 22.77 +/- 3.26) and the common bile duct (CBD: 60.44 +/- 5.99 vs. 40.0 +/- 2.88) and in the half-time of excretion (T1/2) over the liver parenchyma (LP: 120.04 +/- 16.01 vs. 27.37 +/- 2.19), HH (117.61 +/- 14.71 vs. 31.85 +/- 3.99) and CBD (158.11 +/- 9.18 vs. 40.1 +/- 6.24), indicating a complete spasm at the level of the sphincter of Oddi. Glyceryl trinitrate infusion completely normalized the prostigmine-morphine-induced alterations in these quantitative parameters (TmaX over the LP: 11.33 +/- 1.13; over the HH: 18.88 +/- 1.48; and over the CBD: 36.22 +/- 1.92; and T1/2 over the LP: 28.21 +/- 1.83; over the HH: 33.42 +/- 3.10; and over the CBD: 41.66 +/- 6.33), suggesting an effective sphincter-relaxing effect of glyceryl trinitrate. CONCLUSION: These results provide the first evidence of the effectiveness of glyceryl trinitrate on the morphine-induced sphincter of Oddi spasm in humans. Since glyceryl trinitrate is able to overcome even the drastic effect of morphine, it might be of relevance in the treatment of sphincter of Oddi dyskinesia.
9431903	10	29	glyceryl trinitrate	Chemical	D005996
9431903	37	60	sphincter of Oddi spasm	Disease	D046628|D013035	sphincter of Oddi spasm|spasm
9431903	71	82	prostigmine	Chemical	D009388
9431903	83	91	morphine	Chemical	D009020
9431903	147	166	glyceryl trinitrate	Chemical	D005996
9431903	174	185	prostigmine	Chemical	D009388
9431903	186	194	morphine	Chemical	D009020
9431903	203	226	sphincter of Oddi spasm	Disease	D046628|D013035	sphincter of Oddi spasm|spasm
9431903	270	298	sphincter of Oddi dyskinesia	Disease	D046628
9431903	308	331	Sphincter of Oddi spasm	Disease	D046628|D013035	Sphincter of Oddi spasm|spasm
9431903	347	358	prostigmine	Chemical	D009388
9431903	359	367	morphine	Chemical	D009020
9431903	391	402	prostigmine	Chemical	D009388
9431903	429	437	morphine	Chemical	D009020
9431903	554	573	glyceryl trinitrate	Chemical	D005996
9431903	584	596	Nitrolingual	Chemical	D005996
9431903	636	647	Prostigmine	Chemical	D009388
9431903	648	656	morphine	Chemical	D009020
9431903	1080	1085	spasm	Disease	D013035
9431903	1125	1144	Glyceryl trinitrate	Chemical	D005996
9431903	1180	1191	prostigmine	Chemical	D009388
9431903	1192	1200	morphine	Chemical	D009020
9431903	1507	1526	glyceryl trinitrate	Chemical	D005996
9431903	1605	1624	glyceryl trinitrate	Chemical	D005996
9431903	1632	1640	morphine	Chemical	D009020
9431903	1649	1672	sphincter of Oddi spasm	Disease	D046628|D013035	sphincter of Oddi spasm|spasm
9431903	1690	1709	glyceryl trinitrate	Chemical	D005996
9431903	1757	1765	morphine	Chemical	D009020
9431903	1812	1840	sphincter of Oddi dyskinesia	Disease	D046628
9431903	CID	D009020	D046628
9431903	CID	D009388	D013035
9431903	CID	D009020	D013035
9431903	CID	D009388	D046628

8665051|t|Effects of acute steroid administration on ventilatory and peripheral muscles in rats.
8665051|a|Occasional case reports have shown that acute myopathy may occur in patients treated with massive doses of corticosteroids. The mechanism of this myopathy is poorly understood. Therefore, 60 male rats were randomly assigned to receive daily injection of saline (C), methylprednisolone (M), or triamcinolone (T) 80 mg/kg/d for 5 d. Nutritional intake, measured daily in 15 animals, showed a significant reduction of food intake in the steroid-treated groups (-50 and -79% in M and T, respectively). This was associated with a similar loss in body weight. In the 45 remaining animals, diaphragm contractility and histopathologic features of several muscles were studied. Weights of respiratory and peripheral muscles were similarly decreased after steroid treatment. Maximal twitches of the diaphragm were lower in the C group (653 +/- 174 g/cm(2)) than in the M group (837 +/- 171 g/cm(2); p < 0.05) and the T group (765 +/- 145 g/cm(2), NS). Half-relaxation time was prolonged in both steroid groups, and time to peak tension was longer with M, whereas tetanic tensions were similar. Steroid treatment also induced a leftward shift of the force-frequency curve at 25 and 50 Hz when compared with saline treatment (p < 0.05). ATPase staining of the diaphragm, scalenus medius, and gastrocnemius showed type IIb fiber atrophy in the steroid groups and also diaphragmatic type IIa atrophy with T, whereas histologic examinations revealed a normal muscular pattern with absence of necrosis. Finally, a pair-fed (PF) study, performed in 18 rats (C, T, and PF), showed that muscle atrophy was considerably less pronounced in PF animals than in T-treated animals. We conclude that (1) short-term treatment with massive doses of steroids induced severe respiratory and limb muscle wasting; (2) both types of steroids induced predominantly type IIb atrophy, resulting in the expected alterations in diaphragm contractile properties; (3) neither steroid caused muscle necrosis; (4) type IIb atrophy was not caused by acute nutritional deprivation alone.
8665051	17	24	steroid	Chemical	D013256
8665051	133	141	myopathy	Disease	D009135
8665051	194	209	corticosteroids	Chemical	D000305
8665051	233	241	myopathy	Disease	D009135
8665051	353	371	methylprednisolone	Chemical	D008775
8665051	373	374	M	Chemical	D008775
8665051	380	393	triamcinolone	Chemical	D014221
8665051	395	396	T	Chemical	D014221
8665051	489	513	reduction of food intake	Disease	D000855
8665051	521	528	steroid	Chemical	D013256
8665051	561	562	M	Chemical	D008775
8665051	567	568	T	Chemical	D014221
8665051	620	639	loss in body weight	Disease	D015431
8665051	833	840	steroid	Chemical	D013256
8665051	946	947	M	Chemical	D008775
8665051	994	995	T	Chemical	D014221
8665051	1072	1079	steroid	Chemical	D013256
8665051	1129	1130	M	Chemical	D008775
8665051	1140	1147	tetanic	Disease	D013746
8665051	1171	1178	Steroid	Chemical	D013256
8665051	1403	1410	atrophy	Disease	D009133
8665051	1418	1425	steroid	Chemical	D013256
8665051	1465	1472	atrophy	Disease	D009133
8665051	1478	1479	T	Chemical	D014221
8665051	1564	1572	necrosis	Disease	D009336
8665051	1631	1632	T	Chemical	D014221
8665051	1655	1669	muscle atrophy	Disease	D009133
8665051	1725	1726	T	Chemical	D014221
8665051	1808	1816	steroids	Chemical	D013256
8665051	1887	1895	steroids	Chemical	D013256
8665051	1927	1934	atrophy	Disease	D001284
8665051	2023	2030	steroid	Chemical	D013256
8665051	2045	2053	necrosis	Disease	D009336
8665051	2068	2075	atrophy	Disease	D009133
8665051	CID	D014221	D015431
8665051	CID	D008775	D015431
8665051	CID	D014221	D009133
8665051	CID	D008775	D009133
8665051	CID	D008775	D000855
8665051	CID	D014221	D000855

7785794|t|Refractory cardiogenic shock and complete heart block after verapamil SR and metoprolol treatment. A case report.
7785794|a|A seventy-eight-year-old woman presented with complete heart block and refractory hypotension two days after a therapeutic dose of sustained-release verapamil with concomitant use of metoprolol. The patient continued to remain hypotensive with complete heart block, even with multiple uses of intravenous atropine as well as high doses of pressor agents such as dopamine and dobutamine. However, shortly after the use of intravenous calcium chloride, the refractory hypotension and complete heart block resolved.
7785794	11	28	cardiogenic shock	Disease	D012770
7785794	42	53	heart block	Disease	D006327
7785794	60	69	verapamil	Chemical	D014700
7785794	77	87	metoprolol	Chemical	D008790
7785794	169	180	heart block	Disease	D006327
7785794	196	207	hypotension	Disease	D007022
7785794	263	272	verapamil	Chemical	D014700
7785794	297	307	metoprolol	Chemical	D008790
7785794	341	352	hypotensive	Disease	D007022
7785794	367	378	heart block	Disease	D006327
7785794	419	427	atropine	Chemical	D001285
7785794	476	484	dopamine	Chemical	D004298
7785794	489	499	dobutamine	Chemical	D004280
7785794	547	563	calcium chloride	Chemical	D002122
7785794	580	591	hypotension	Disease	D007022
7785794	605	616	heart block	Disease	D006327
7785794	CID	D008790	D007022
7785794	CID	D014700	D006327
7785794	CID	D014700	D007022
7785794	CID	D008790	D006327

8958188|t|A phase I clinical study of the antipurine antifolate lometrexol (DDATHF) given with oral folic acid.
8958188|a|Lometrexol is an antifolate which inhibits glycinamide ribonucleotide formyltransferase (GARFT), an enzyme essential for de novo purine synthesis. Extensive experimental and limited clinical data have shown that lometrexol has activity against tumours which are refractory to other drugs, notably methotrexate. However, the initial clinical development of lometrexol was curtailed because of severe and cumulative antiproliferative toxicities. Preclinical murine studies demonstrated that the toxicity of lometrexol can be prevented by low dose folic acid administration, i.e. for 7 days prior to and 7 days following a single bolus dose. This observation prompted a Phase I clinical study of lometrexol given with folic acid supplementation which has confirmed that the toxicity of lometrexol can be markedly reduced by folic acid supplementation. Thrombocytopenia and mucositis were the major toxicities. There was no clear relationship between clinical toxicity and the extent of plasma folate elevation. Associated studies demonstrated that lometrexol plasma pharmacokinetics were not altered by folic acid administration indicating that supplementation is unlikely to reduce toxicity by enhancing lometrexol plasma clearance. The work described in this report has identified for the first time a clinically acceptable schedule for the administration of a GARFT inhibitor. This information will facilitate the future evaluation of this class of compounds in cancer therapy.
8958188	32	42	antipurine	Chemical	D000983
8958188	54	64	lometrexol	Chemical	C045894
8958188	66	72	DDATHF	Chemical	C045894
8958188	90	100	folic acid	Chemical	D005492
8958188	102	112	Lometrexol	Chemical	C045894
8958188	145	171	glycinamide ribonucleotide	Chemical	C402896
8958188	231	237	purine	Chemical	D011687
8958188	314	324	lometrexol	Chemical	C045894
8958188	346	353	tumours	Disease	D009369
8958188	399	411	methotrexate	Chemical	D008727
8958188	458	468	lometrexol	Chemical	C045894
8958188	534	544	toxicities	Disease	D064420
8958188	595	603	toxicity	Disease	D064420
8958188	607	617	lometrexol	Chemical	C045894
8958188	647	657	folic acid	Chemical	D005492
8958188	795	805	lometrexol	Chemical	C045894
8958188	817	827	folic acid	Chemical	D005492
8958188	873	881	toxicity	Disease	D064420
8958188	885	895	lometrexol	Chemical	C045894
8958188	923	933	folic acid	Chemical	D005492
8958188	951	967	Thrombocytopenia	Disease	D013921
8958188	972	981	mucositis	Disease	D052016
8958188	997	1007	toxicities	Disease	D064420
8958188	1058	1066	toxicity	Disease	D064420
8958188	1092	1098	folate	Chemical	D005492
8958188	1147	1157	lometrexol	Chemical	C045894
8958188	1202	1212	folic acid	Chemical	D005492
8958188	1282	1290	toxicity	Disease	D064420
8958188	1304	1314	lometrexol	Chemical	C045894
8958188	1564	1570	cancer	Disease	D009369
8958188	CID	C045894	D052016
8958188	CID	C045894	D013921

2557556|t|Involvement of the mu-opiate receptor in peripheral analgesia.
2557556|a|The intradermal injection of mu (morphine, Tyr-D-Ala-Gly-NMe-Phe-Gly-ol and morphiceptin), kappa (trans-3,4-dichloro-N-methyl-N[2-(1-pyrrolidinyl) cyclohexyl]benzeneactemide) and delta ([D-Pen2.5]-enkephalin and [D-Ser2]-[Leu]enkephalin-Thr) selective opioid-agonists, by themselves, did not significantly affect the mechanical nociceptive threshold in the hindpaw of the rat. Intradermal injection of mu, but not delta or kappa opioid-agonists, however, produced dose-dependent inhibition of prostaglandin E2-induced hyperalgesia. The analgesic effect of the mu-agonist morphine was dose-dependently antagonized by naloxone and prevented by co-injection of pertussis toxin. Morphine did not, however, alter the hyperalgesia induced by 8-bromo cyclic adenosine monophosphate. We conclude that the analgesic action of opioids on the peripheral terminals of primary afferents is via a binding site with characteristics of the mu-opioid receptor and that this action is mediated by inhibition of the cyclic adenosine monophosphate second messenger system.
2557556	52	61	analgesia	Disease	D000699
2557556	96	104	morphine	Chemical	D009020
2557556	106	134	Tyr-D-Ala-Gly-NMe-Phe-Gly-ol	Chemical	D020875
2557556	139	151	morphiceptin	Chemical	C028889
2557556	161	236	trans-3,4-dichloro-N-methyl-N[2-(1-pyrrolidinyl) cyclohexyl]benzeneactemide	Chemical	D019900
2557556	249	270	[D-Pen2.5]-enkephalin	Chemical	D020881
2557556	275	303	[D-Ser2]-[Leu]enkephalin-Thr	Chemical	C034318
2557556	556	572	prostaglandin E2	Chemical	D015232
2557556	581	593	hyperalgesia	Disease	D006930
2557556	634	642	morphine	Chemical	D009020
2557556	679	687	naloxone	Chemical	D009270
2557556	738	746	Morphine	Chemical	D009020
2557556	775	787	hyperalgesia	Disease	D006930
2557556	799	837	8-bromo cyclic adenosine monophosphate	Chemical	D015124
2557556	1060	1090	cyclic adenosine monophosphate	Chemical	D000242
2557556	CID	D015124	D006930
2557556	CID	D015232	D006930

15580403|t|Adequate timing of ribavirin reduction in patients with hemolysis during combination therapy of interferon and ribavirin for chronic hepatitis C.
15580403|a|BACKGROUND: Hemolytic anemia is one of the major adverse events of the combination therapy of interferon and ribavirin. Because of ribavirin-related hemolytic anemia, dose reduction is a common event in this therapy. In this clinical retrospective cohort study we have examined the suitable timing of ribavirin reduction in patients with hemolysis during combination therapy. METHODS: Thirty-seven of 160 patients who had HCV-genotype 1b, had high virus load, and received 24-week combination therapy developed anemia with hemoglobin level <10 g/dl or anemia-related signs during therapy. After that, these 37 patients were reduced one tablet of ribavirin (200 mg) per day. After reduction of ribavirin, 27 of 37 patients could continue combination therapy for a total of 24 weeks (group A). However, 10 of 37 patients with reduction of ribavirin could not continue combination therapy because their <8.5 g/dl hemoglobin values decreased to or anemia-related severe side effects occurred (group B). We assessed the final efficacy and safety after reduction of ribavirin in groups A and B. RESULTS: A sustained virological response (SVR) was 29.6% (8/27) in group A and 10% (1/10) in group B, respectively. A 34.4% (12/27) of SVR + biological response in group A was higher than 10% (1/10) in group B ( P = 0.051), with slight significance. With respect to hemoglobin level at the time of ribavirin reduction, a rate of continuation of therapy in patients with > or =10 g/dl hemoglobin was higher than that in patients with <10 g/dl ( P = 0.036). CONCLUSIONS: Reduction of ribavirin at hemoglobin level > or =10 g/dl is suitable in terms of efficacy and side effects.
15580403	19	28	ribavirin	Chemical	D012254
15580403	56	65	hemolysis	Disease	D006461
15580403	96	106	interferon	Chemical	D007372
15580403	111	120	ribavirin	Chemical	D012254
15580403	125	144	chronic hepatitis C	Disease	D019698
15580403	158	174	Hemolytic anemia	Disease	D000743
15580403	240	250	interferon	Chemical	D007372
15580403	255	264	ribavirin	Chemical	D012254
15580403	277	286	ribavirin	Chemical	D012254
15580403	295	311	hemolytic anemia	Disease	D000743
15580403	447	456	ribavirin	Chemical	D012254
15580403	484	493	hemolysis	Disease	D006461
15580403	657	663	anemia	Disease	D000740
15580403	698	704	anemia	Disease	D000740
15580403	792	801	ribavirin	Chemical	D012254
15580403	839	848	ribavirin	Chemical	D012254
15580403	983	992	ribavirin	Chemical	D012254
15580403	1090	1096	anemia	Disease	D000740
15580403	1206	1215	ribavirin	Chemical	D012254
15580403	1534	1543	ribavirin	Chemical	D012254
15580403	1718	1727	ribavirin	Chemical	D012254
15580403	CID	D007372	D000743
15580403	CID	D012254	D000743

15075188|t|Increased expression and apical targeting of renal ENaC subunits in puromycin aminonucleoside-induced nephrotic syndrome in rats.
15075188|a|Nephrotic syndrome is often accompanied by sodium retention and generalized edema. However, the molecular basis for the decreased renal sodium excretion remains undefined. We hypothesized that epithelial Na channel (ENaC) subunit dysregulation may be responsible for the increased sodium retention. An experimental group of rats was treated with puromycin aminonucleoside (PAN; 180 mg/kg iv), whereas the control group received only vehicle. After 7 days, PAN treatment induced significant proteinuria, hypoalbuminemia, decreased urinary sodium excretion, and extensive ascites. The protein abundance of alpha-ENaC and beta-ENaC was increased in the inner stripe of the outer medulla (ISOM) and in the inner medulla (IM) but was not altered in the cortex. gamma-ENaC abundance was increased in the cortex, ISOM, and IM. Immunoperoxidase brightfield- and laser-scanning confocal fluorescence microscopy demonstrated increased targeting of alpha-ENaC, beta-ENaC, and gamma-ENaC subunits to the apical plasma membrane in the distal convoluted tubule (DCT2), connecting tubule, and cortical and medullary collecting duct segments. Immunoelectron microscopy further revealed an increased labeling of alpha-ENaC in the apical plasma membrane of cortical collecting duct principal cells of PAN-treated rats, indicating enhanced apical targeting of alpha-ENaC subunits. In contrast, the protein abundances of Na(+)/H(+) exchanger type 3 (NHE3), Na(+)-K(+)-2Cl(-) cotransporter (BSC-1), and thiazide-sensitive Na(+)-Cl(-) cotransporter (TSC) were decreased. Moreover, the abundance of the alpha(1)-subunit of the Na-K-ATPase was decreased in the cortex and ISOM, but it remained unchanged in the IM. In conclusion, the increased or sustained expression of ENaC subunits combined with increased apical targeting in the DCT2, connecting tubule, and collecting duct are likely to play a role in the sodium retention associated with PAN-induced nephrotic syndrome. The decreased abundance of NHE3, BSC-1, TSC, and Na-K-ATPase may play a compensatory role to promote sodium excretion.
15075188	68	93	puromycin aminonucleoside	Chemical	D011692
15075188	102	120	nephrotic syndrome	Disease	D009404
15075188	130	148	Nephrotic syndrome	Disease	D009404
15075188	173	179	sodium	Chemical	D012964
15075188	206	211	edema	Disease	D004487
15075188	266	272	sodium	Chemical	D012964
15075188	334	336	Na	Chemical	D012964
15075188	411	417	sodium	Chemical	D012964
15075188	476	501	puromycin aminonucleoside	Chemical	D011692
15075188	503	506	PAN	Chemical	D011692
15075188	586	589	PAN	Chemical	D011692
15075188	620	631	proteinuria	Disease	D011507
15075188	633	648	hypoalbuminemia	Disease	D034141
15075188	668	674	sodium	Chemical	D012964
15075188	700	707	ascites	Disease	D001201
15075188	1413	1416	PAN	Chemical	D011692
15075188	1531	1533	Na	Chemical	D012964
15075188	1537	1538	H	Chemical	D006859
15075188	1567	1569	Na	Chemical	D012964
15075188	1573	1574	K	Chemical	D011188
15075188	1579	1581	Cl	Chemical	D002713
15075188	1612	1620	thiazide	Chemical	D049971
15075188	1631	1633	Na	Chemical	D012964
15075188	1637	1639	Cl	Chemical	D002713
15075188	1734	1736	Na	Chemical	D012964
15075188	1737	1738	K	Chemical	D011188
15075188	2017	2023	sodium	Chemical	D012964
15075188	2050	2053	PAN	Chemical	D011692
15075188	2062	2080	nephrotic syndrome	Disease	D009404
15075188	2131	2133	Na	Chemical	D012964
15075188	2134	2135	K	Chemical	D011188
15075188	2183	2189	sodium	Chemical	D012964
15075188	CID	D011692	D001201
15075188	CID	D011692	D009404
15075188	CID	D011692	D011507
15075188	CID	D011692	D034141

14745746|t|Does hormone therapy for the treatment of breast cancer have a detrimental effect on memory and cognition? A pilot study.
14745746|a|This pilot study examines whether hormone therapy for breast cancer affects cognition. Patients participating in a randomised trial of anastrozole, tamoxifen alone or combined (ATAC) (n=94) and a group of women without breast cancer (n=35) completed a battery of neuropsychological measures. Compared with the control group, the patients were impaired on a processing speed task (p=0.032) and on a measure of immediate verbal memory (p=0.026) after controlling for the use of hormone replacement therapy in both groups. Patient group performance was not significantly related to length of treatment or measures of psychological morbidity. The results showed specific impairments in processing speed and verbal memory in women receiving hormonal therapy for the treatment of breast cancer. Verbal memory may be especially sensitive to changes in oestrogen levels, a finding commonly reported in studies of hormone replacement therapy in healthy women. In view of the increased use of hormone therapies in an adjuvant and preventative setting their impact on cognitive functioning should be investigated more thoroughly.
14745746	42	55	breast cancer	Disease	D001943
14745746	63	105	detrimental effect on memory and cognition	Disease	D008569|D003072	detrimental effect on memory|detrimental effect on cognition
14745746	176	189	breast cancer	Disease	D001943
14745746	257	268	anastrozole	Chemical	C090450
14745746	270	279	tamoxifen	Chemical	D013629
14745746	341	354	breast cancer	Disease	D001943
14745746	896	909	breast cancer	Disease	D001943
14745746	967	976	oestrogen	Chemical	D004967
14745746	CID	D013629	D008569
14745746	CID	C090450	D008569
14745746	CID	C090450	D003072
14745746	CID	D013629	D003072

11208990|t|Association of nitric oxide production and apoptosis in a model of experimental nephropathy.
11208990|a|BACKGROUND: In recent studies increased amounts of nitric oxide (NO) and apoptosis have been implicated in various pathological conditions in the kidney. We have studied the role of NO and its association with apoptosis in an experimental model of nephrotic syndrome induced by a single injection of adriamycin (ADR). METHODS: The alteration in the NO pathway was assessed by measuring nitrite levels in serum/urine and by evaluating the changes in vascular reactivity of the isolated perfused rat kidney (IPRK) system. Rats were stratified into control groups and ADR-induced nephropathy groups. These two groups were then divided into: group 1, animals receiving saline; and group 2, animals receiving aminoguanidine (AG) which is a specific inhibitor of inducible-NO synthase. On day 21, rats were sacrificed after obtaining material for biochemical analysis. RESULTS: Histopathological examination of the kidneys of rats treated with ADR revealed focal areas of mesangial proliferation and mild tubulointerstitial inflammation. They also had significantly higher levels of proteinuria compared with control and treatment groups (P < 0.05). Urine nitrite levels were significantly increased in the ADR-nephropathy group (P < 0.05). In the IPRK phenylephrine and acetylcholine related responses were significantly impaired in the ADR-nephropathy group. Apoptosis was not detected in controls. However, in the ADR-nephropathy group, numerous apoptotic cells were identified in the tubulointerstitial areas. Double staining revealed numerous interstitial apoptotic cells to stain for ED1, a marker for monocytes/macrophages. Treatment with AG prevented the impairment of renal vascular bed responses and reduced both urine nitrite levels and apoptosis to control levels. CONCLUSION: We suggest that interactions between NO and apoptosis are important in the pathogenesis of the ADR-induced nephrosis.
11208990	15	27	nitric oxide	Chemical	D009569
11208990	80	91	nephropathy	Disease	D007674
11208990	144	156	nitric oxide	Chemical	D009569
11208990	158	160	NO	Chemical	D009569
11208990	275	277	NO	Chemical	D009569
11208990	341	359	nephrotic syndrome	Disease	D009404
11208990	393	403	adriamycin	Chemical	D004317
11208990	405	408	ADR	Chemical	D004317
11208990	442	444	NO	Chemical	D009569
11208990	479	486	nitrite	Chemical	D009573
11208990	658	661	ADR	Chemical	D004317
11208990	670	681	nephropathy	Disease	D007674
11208990	797	811	aminoguanidine	Chemical	C004479
11208990	813	815	AG	Chemical	C004479
11208990	860	862	NO	Chemical	D009569
11208990	1031	1034	ADR	Chemical	D004317
11208990	1059	1082	mesangial proliferation	Disease	C537346
11208990	1092	1123	tubulointerstitial inflammation	Disease	D009395
11208990	1170	1181	proteinuria	Disease	D011507
11208990	1243	1250	nitrite	Chemical	D009573
11208990	1294	1297	ADR	Chemical	D004317
11208990	1298	1309	nephropathy	Disease	D007674
11208990	1340	1353	phenylephrine	Chemical	D010656
11208990	1358	1371	acetylcholine	Chemical	D000109
11208990	1425	1428	ADR	Chemical	D004317
11208990	1429	1440	nephropathy	Disease	D007674
11208990	1504	1507	ADR	Chemical	D004317
11208990	1508	1519	nephropathy	Disease	D007674
11208990	1733	1735	AG	Chemical	C004479
11208990	1816	1823	nitrite	Chemical	D009573
11208990	1913	1915	NO	Chemical	D009569
11208990	1971	1974	ADR	Chemical	D004317
11208990	1983	1992	nephrosis	Disease	D009401
11208990	CID	D004317	D011507
11208990	CID	D004317	D009404

9201797|t|The attenuating effect of carteolol hydrochloride, a beta-adrenoceptor antagonist, on neuroleptic-induced catalepsy in rats.
9201797|a|It is known that beta-adrenoceptor antagonists are effective in the treatment of akathisia, one of the extrapyramidal side effects that occur during neuroleptic treatment. Neuroleptic-induced catalepsy, a model of neuroleptic-induced extrapyramidal side effects, was considered suitable as a model for predicting neuroleptic-induced akathisia in humans, although neuroleptic-induced catalepsy was not considered a specific test for neuroleptic-induced akathisia. Therefore, the effects of carteolol, a beta-adrenoceptor antagonist, on haloperidol-induced catalepsy in rats were behaviorally studied and compared with those of propranolol and biperiden, a muscarinic receptor antagonist. Carteolol, as well as propranolol and biperiden, inhibited the haloperidol-induced catalepsy. The inhibitory effect of carteolol was almost comparable to that of propranolol, but was weaker than that of biperiden. Carteolol did not evoke postsynaptic dopamine receptor-stimulating behavioral signs such as stereotypy and hyperlocomotion in rats. Carteolol did not antagonize the inhibitory effects of haloperidol on apomorphine-induced stereotypy and locomotor activity in rats. In addition, carteolol did not evoke 5-HT1A receptor-stimulating behavioral signs such as flat body posture and forepaw treading and did not inhibit 5-hydroxytryptophan-induced head twitch in rats. Finally, carteolol did not inhibit physostigmine-induced lethality in rats. These results strongly suggest that carteolol improves haloperidol-induced catalepsy via its beta-adrenoceptor antagonistic activity and is expected to be effective in the treatment of akathisia without attenuating neuroleptic-induced antipsychotic effects due to its postsynaptic dopamine receptor antagonistic activity.
9201797	26	49	carteolol hydrochloride	Chemical	D002354
9201797	106	115	catalepsy	Disease	D002375
9201797	206	215	akathisia	Disease	D017109
9201797	317	326	catalepsy	Disease	D002375
9201797	458	467	akathisia	Disease	D017109
9201797	508	517	catalepsy	Disease	D002375
9201797	577	586	akathisia	Disease	D017109
9201797	614	623	carteolol	Chemical	D002354
9201797	660	671	haloperidol	Chemical	D006220
9201797	680	689	catalepsy	Disease	D002375
9201797	751	762	propranolol	Chemical	D011433
9201797	767	776	biperiden	Chemical	D001712
9201797	812	821	Carteolol	Chemical	D002354
9201797	834	845	propranolol	Chemical	D011433
9201797	850	859	biperiden	Chemical	D001712
9201797	875	886	haloperidol	Chemical	D006220
9201797	895	904	catalepsy	Disease	D002375
9201797	931	940	carteolol	Chemical	D002354
9201797	974	985	propranolol	Chemical	D011433
9201797	1015	1024	biperiden	Chemical	D001712
9201797	1026	1035	Carteolol	Chemical	D002354
9201797	1063	1071	dopamine	Chemical	D004298
9201797	1133	1148	hyperlocomotion	Disease	D009069
9201797	1158	1167	Carteolol	Chemical	D002354
9201797	1213	1224	haloperidol	Chemical	D006220
9201797	1228	1239	apomorphine	Chemical	D001058
9201797	1304	1313	carteolol	Chemical	D002354
9201797	1440	1459	5-hydroxytryptophan	Chemical	D006916
9201797	1498	1507	carteolol	Chemical	D002354
9201797	1524	1537	physostigmine	Chemical	D010830
9201797	1601	1610	carteolol	Chemical	D002354
9201797	1620	1631	haloperidol	Chemical	D006220
9201797	1640	1649	catalepsy	Disease	D002375
9201797	1750	1759	akathisia	Disease	D017109
9201797	1846	1854	dopamine	Chemical	D004298
9201797	CID	D006220	D002375

8267029|t|Penicillamine-induced rapidly progressive glomerulonephritis in a patient with rheumatoid arthritis.
8267029|a|A 67-year-old woman with rheumatoid arthritis presented rapidly progressive glomerulonephritis (RPGN) after 5 months of D-penicillamine (250 mg/day) treatment. Light microscopy study showed severe glomerulonephritis with crescent formation in 60% of the glomeruli and infiltration of inflammatory cells in the wall of an arteriole. Immunofluorescence revealed scanty granular IgG, IgA and C3 deposits along the capillary walls and mesangium. The patient was treated with steroid pulse, plasmapheresis, cyclophosphamide and antiplatelet agents. A complete recovery of renal function was achieved in a few weeks. This new case of RPGN in the course of D-penicillamine treatment emphasizes the need for frequent monitoring of renal function and evaluation of urinary sediment and proteinuria in these patients. The prompt discontinuation of D-penicillamine and vigorous treatment measures could allow for a good prognosis as in this case.
8267029	0	13	Penicillamine	Chemical	D010396
8267029	42	60	glomerulonephritis	Disease	D005921
8267029	79	99	rheumatoid arthritis	Disease	D001172
8267029	126	146	rheumatoid arthritis	Disease	D001172
8267029	177	195	glomerulonephritis	Disease	D005921
8267029	197	201	RPGN	Disease	D005921
8267029	221	236	D-penicillamine	Chemical	D010396
8267029	298	316	glomerulonephritis	Disease	D005921
8267029	572	579	steroid	Chemical	D013256
8267029	603	619	cyclophosphamide	Chemical	D003520
8267029	624	643	antiplatelet agents	Chemical	D010975
8267029	729	733	RPGN	Disease	D005921
8267029	751	766	D-penicillamine	Chemical	D010396
8267029	878	889	proteinuria	Disease	D011507
8267029	939	954	D-penicillamine	Chemical	D010396
8267029	CID	D010396	D005921

2528969|t|Nature, time course and dose dependence of zidovudine-related side effects: results from the Multicenter Canadian Azidothymidine Trial.
2528969|a|To characterize the nature, time course and dose dependency of zidovudine-related side effects, we undertook a multicenter, prospective, dose-range finding study. Our study group consisted of 74 HIV-positive homosexual men belonging to groups II B, III and IV C2 from the Centers for Disease Control (CDC) classification of HIV disease. Following a 3-week observation period, volunteers were treated with zidovudine 600 mg/day for 18 weeks, 900 mg/day for 9 weeks and 1200 mg/day for 9 weeks, followed by a washout period of 6 weeks after which they were re-started on 1200 mg/day or the highest tolerated dose at 8-hourly intervals. Subjects were randomly assigned to 4-hourly or 8-hourly regimens within CDC groups while taking 600 and 1200 mg/day. Clinical and laboratory evaluations were performed at 3-week intervals. Symptomatic adverse effects were present in 96% of subjects, most commonly nausea (64%), fatigue (55%) and headache (49%). These were generally self-limited, reappearing briefly at each dose increment. A decrease in hemoglobin occurred shortly after initiation of therapy. This was not dose dependent and reversed rapidly upon discontinuation of treatment. A red blood cell count decrease, a mean cell volume increase and a granulocyte count decrease developed early in a dose-independent fashion, reverting at least partially during the washout phase. The decrease in reticulocyte count was dose related between 600 and 900 mg/day with no further change when the dose was escalated to 1200 mg/day. Bone marrow changes occurred rapidly as demonstrated by megaloblastosis in 95% of 65 specimens at week 18.(ABSTRACT TRUNCATED AT 250 WORDS)
2528969	43	53	zidovudine	Chemical	D015215
2528969	114	128	Azidothymidine	Chemical	D015215
2528969	199	209	zidovudine	Chemical	D015215
2528969	460	471	HIV disease	Disease	D015658
2528969	541	551	zidovudine	Chemical	D015215
2528969	1034	1040	nausea	Disease	D009325
2528969	1048	1055	fatigue	Disease	D005221
2528969	1066	1074	headache	Disease	D006261
2528969	1714	1729	megaloblastosis	Disease	-1
2528969	CID	D015215	D009325
2528969	CID	D015215	D005221
2528969	CID	D015215	D006261

384871|t|Bilateral optic neuropathy due to combined ethambutol and isoniazid treatment.
384871|a|The case of a 40-year-old patient who underwent an unsuccessful cadaver kidney transplantation and was treated with ethambutol and isoniazid is reported. A bilateral retrobulbar neuropathy with an unusual central bitemporal hemianopic scotoma was found. Ethambutol was stopped and only small improvement of the visual acuity followed. Isoniazid was discontinued later, followed by a dramatic improvement in the visual acuity. The hazards of optic nerve toxicity due to ethambutol are known. We emphasize the potential danger in the use of ethambutol and isoniazid.
384871	0	26	Bilateral optic neuropathy	Disease	D009901
384871	43	53	ethambutol	Chemical	D004977
384871	58	67	isoniazid	Chemical	D007538
384871	195	205	ethambutol	Chemical	D004977
384871	210	219	isoniazid	Chemical	D007538
384871	235	267	bilateral retrobulbar neuropathy	Disease	D009901
384871	314	321	scotoma	Disease	D012607
384871	333	343	Ethambutol	Chemical	D004977
384871	414	423	Isoniazid	Chemical	D007538
384871	532	540	toxicity	Disease	D064420
384871	548	558	ethambutol	Chemical	D004977
384871	618	628	ethambutol	Chemical	D004977
384871	633	642	isoniazid	Chemical	D007538
384871	CID	D007538	D012607
384871	CID	D004977	D009901
384871	CID	D007538	D009901
384871	CID	D004977	D012607

133615|t|Progestational agents and blood coagulation. VII. Thromboembolic and other complications of oral contraceptive therapy in relationship to pretreatment levels of blood coagulation factors: summary report of a ten-year study.
133615|a|During a ten-year period, 348 women were studied for a total of 5,877 patient months in four separate studies relating oral contraceptives to changes in hematologic parameters. Significant increases in certain factors of the blood coagulation and fibrinolysin systems (factors I,II,VII,VIII,IX, and X and plasminogen) were observed in the treated groups. Severe complications developed in four patients. All four had an abnormal blood coagulation profile, suggesting "hypercoagulability" before initiation of therapy. Some of these findings represented the most extreme abnormalities seen in the entire group of patients; some increased further during therapy. One of these patients developed a myocardial infarction before receiving any medication, shortly after the base-line values were obtained. One patient developed retinopathy 19 months after she began therapy, and another developed thrombophlebitis after 27 months of therapy. The fourth patient developed thrombophlebitis 14 days after initiation of contraceptive therapy. All four patients were of the A or AB blood group. Previous studies suggested the possiblility of increased propensity for thromboembolic episodes in patients possessing the A antigen. It appears from these data that hematologic work-ups may be useful in women who are about to start long-term oral contraceptive therapy.
133615	26	43	blood coagulation	Disease	D001778
133615	50	64	Thromboembolic	Disease	D013923
133615	92	110	oral contraceptive	Chemical	D003276
133615	161	178	blood coagulation	Disease	D001778
133615	343	362	oral contraceptives	Chemical	D003276
133615	449	466	blood coagulation	Disease	D001778
133615	653	670	blood coagulation	Disease	D001778
133615	692	710	hypercoagulability	Disease	D019851
133615	919	940	myocardial infarction	Disease	D009203
133615	1046	1057	retinopathy	Disease	D012164
133615	1115	1131	thrombophlebitis	Disease	D013924
133615	1189	1205	thrombophlebitis	Disease	D013924
133615	1380	1403	thromboembolic episodes	Disease	D013923
133615	1551	1569	oral contraceptive	Chemical	D003276
133615	CID	D003276	D001778
133615	CID	D003276	D012164
133615	CID	D003276	D013924
133615	CID	D003276	D009203

17263743|t|Cardiac arrest in a child with cerebral palsy undergoing sevoflurane induction of anesthesia after preoperative clonidine.
17263743|a|Clonidine is a frequently administered alpha2-adrenergic agonist which can decrease heart rate and blood pressure. We present a case of a 5-year-old child with cerebral palsy and seizure disorder, receiving clonidine for restlessness, who presented for placement of a baclofen pump. Without the knowledge of the medical personnel, the patient's mother administered three doses of clonidine during the evening before and morning of surgery to reduce anxiety. During induction of anesthesia, the patient developed bradycardia and hypotension requiring cardiac resuscitation. There are no previous reports of clonidine-associated cardiac arrest in a child undergoing induction of anesthesia.
17263743	0	14	Cardiac arrest	Disease	D006323
17263743	31	45	cerebral palsy	Disease	D002547
17263743	57	68	sevoflurane	Chemical	C009250
17263743	112	121	clonidine	Chemical	D003000
17263743	123	132	Clonidine	Chemical	D003000
17263743	283	297	cerebral palsy	Disease	D002547
17263743	302	318	seizure disorder	Disease	D004827
17263743	330	339	clonidine	Chemical	D003000
17263743	344	356	restlessness	Disease	D011595
17263743	391	399	baclofen	Chemical	D001418
17263743	503	512	clonidine	Chemical	D003000
17263743	572	579	anxiety	Disease	D001008
17263743	635	646	bradycardia	Disease	D001919
17263743	651	662	hypotension	Disease	D007022
17263743	729	738	clonidine	Chemical	D003000
17263743	750	764	cardiac arrest	Disease	D006323
17263743	CID	D003000	D007022
17263743	CID	D003000	D001919
17263743	CID	D003000	D006323

17241657|t|Effects of UMB24 and (+/-)-SM 21, putative sigma2-preferring antagonists, on behavioral toxic and stimulant effects of cocaine in mice.
17241657|a|Earlier studies have demonstrated that antagonism of sigma1 receptors attenuates the convulsive, lethal, locomotor stimulatory and rewarding actions of cocaine in mice. In contrast, the contribution of sigma2 receptors is unclear because experimental tools to selectively target this subtype are unavailable. To begin addressing this need, we characterized UMB24 (1-(2-phenethyl)-4-(2-pyridyl)-piperazine) and (+/-)-SM 21 (3alpha-tropanyl-2-(4-chorophenoxy)butyrate) in receptor binding and behavioral studies. Receptor binding studies confirmed that UMB24 and (+/-)-SM 21 display preferential affinity for sigma2 over sigma1 receptors. In behavioral studies, pretreatment of Swiss Webster mice with UMB24 or (+/-)-SM 21 significantly attenuated cocaine-induced convulsions and locomotor activity, but not lethality. When administered alone, (+/-)-SM 21 produced no significant effects compared to control injections of saline, but UMB24 had locomotor depressant actions. Together, the data suggest that sigma2 receptor antagonists have the potential to attenuate some of the behavioral effects of cocaine, and further development of more selective, high affinity ligands are warranted.
17241657	11	16	UMB24	Chemical	C519696
17241657	27	32	SM 21	Chemical	C107044
17241657	119	126	cocaine	Chemical	D003042
17241657	221	231	convulsive	Disease	D012640
17241657	288	295	cocaine	Chemical	D003042
17241657	493	498	UMB24	Chemical	C519696
17241657	500	540	1-(2-phenethyl)-4-(2-pyridyl)-piperazine	Chemical	C519696
17241657	552	557	SM 21	Chemical	C107044
17241657	559	601	3alpha-tropanyl-2-(4-chorophenoxy)butyrate	Chemical	C107044
17241657	687	692	UMB24	Chemical	C519696
17241657	703	708	SM 21	Chemical	C107044
17241657	836	841	UMB24	Chemical	C519696
17241657	851	856	SM 21	Chemical	C107044
17241657	882	889	cocaine	Chemical	D003042
17241657	898	909	convulsions	Disease	D012640
17241657	984	989	SM 21	Chemical	C107044
17241657	1068	1073	UMB24	Chemical	C519696
17241657	1234	1241	cocaine	Chemical	D003042
17241657	CID	D003042	D012640

14982270|t|Methimazole-induced cholestatic jaundice.
14982270|a|Methimazole is a widely used and generally well-tolerated antithyroid agent. A 43-year-old woman had severe jaundice and itching 1 month after receiving methimazole (10 mg tid) and propranolol (20 mg tid) for treatment of hyperthyroidism. The patient continued treatment for another 4 days after the appearance of jaundice until she finished both medications. When seen at the emergency department 2 weeks later, she still had severe icterus, pruritus, and hyperbilirubinemia, formed mainly of the conjugated fraction. Methimazole-induced cholestasis was diagnosed, and propranolol therapy was resumed. Over the following 9 days, the symptoms improved and plasma bilirubin levels were normal after 12 weeks without methimazole. In rare cases within the first few weeks of therapy, this drug can cause severe and reversible cholestatic jaundice. Physicians and patients should be aware of this adverse effect so that, upon occurrence, they can discontinue methimazole therapy and avoid unnecessary invasive procedures.
14982270	0	11	Methimazole	Chemical	D008713
14982270	20	40	cholestatic jaundice	Disease	D041781
14982270	42	53	Methimazole	Chemical	D008713
14982270	150	158	jaundice	Disease	D007565
14982270	163	170	itching	Disease	D011537
14982270	195	206	methimazole	Chemical	D008713
14982270	223	234	propranolol	Chemical	D011433
14982270	264	279	hyperthyroidism	Disease	D006980
14982270	356	364	jaundice	Disease	D007565
14982270	476	483	icterus	Disease	D007565
14982270	485	493	pruritus	Disease	D011537
14982270	499	517	hyperbilirubinemia	Disease	D006932
14982270	561	572	Methimazole	Chemical	D008713
14982270	581	592	cholestasis	Disease	D002779
14982270	612	623	propranolol	Chemical	D011433
14982270	705	714	bilirubin	Chemical	D001663
14982270	757	768	methimazole	Chemical	D008713
14982270	865	885	cholestatic jaundice	Disease	D041781
14982270	997	1008	methimazole	Chemical	D008713
14982270	CID	D008713	D006932
14982270	CID	D008713	D041781
14982270	CID	D008713	D011537

12911170|t|Ciprofloxacin-induced acute interstitial nephritis and autoimmune hemolytic anemia.
12911170|a|Ciprofloxacin has been associated with several side effects including interstitial nephritis and hemolytic anemia. The combination of both side effects is extremely rare. In this report, we describe a case of ciprofloxacin-induced interstitial nephritis and autoimmune hemolytic anemia. Hemolytic anemia improved after stopping the drug and initiation of steroid therapy. Unfortunately, acute interstitial nephritis was irreversible and the patient developed end-stage renal disease.
12911170	0	13	Ciprofloxacin	Chemical	D002939
12911170	28	50	interstitial nephritis	Disease	D009395
12911170	55	82	autoimmune hemolytic anemia	Disease	D000744
12911170	84	97	Ciprofloxacin	Chemical	D002939
12911170	154	176	interstitial nephritis	Disease	D009395
12911170	181	197	hemolytic anemia	Disease	D000743
12911170	293	306	ciprofloxacin	Chemical	D002939
12911170	315	337	interstitial nephritis	Disease	D009395
12911170	342	369	autoimmune hemolytic anemia	Disease	D000744
12911170	371	387	Hemolytic anemia	Disease	D000743
12911170	439	446	steroid	Chemical	D013256
12911170	477	499	interstitial nephritis	Disease	D009395
12911170	543	566	end-stage renal disease	Disease	D007676
12911170	CID	D002939	D000743
12911170	CID	D002939	D007676
12911170	CID	D002939	D009395

11195262|t|Contribution of sodium valproate to the syndrome of inappropriate secretion of antidiuretic hormone.
11195262|a|We report the case of a 62-year-old man who was administered sodium valproate (VPA) and who subsequently developed the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). He had been taking VPA for treatment of idiopathic generalized tonic-clonic convulsions since he was 56 years old. After substituting VPA with zonisamide, the serum sodium level returned to normal. We consider this episode of SIADH to be the result of a combination of factors including a weakness of the central nervous system and the long-term administration of VPA.
11195262	16	32	sodium valproate	Chemical	D014635
11195262	40	99	syndrome of inappropriate secretion of antidiuretic hormone	Disease	D007177
11195262	162	178	sodium valproate	Chemical	D014635
11195262	180	183	VPA	Chemical	D014635
11195262	220	279	syndrome of inappropriate secretion of antidiuretic hormone	Disease	D007177
11195262	281	286	SIADH	Disease	D007177
11195262	308	311	VPA	Chemical	D014635
11195262	352	376	tonic-clonic convulsions	Disease	D004830
11195262	423	426	VPA	Chemical	D014635
11195262	432	442	zonisamide	Chemical	C022189
11195262	454	460	sodium	Chemical	D012964
11195262	515	520	SIADH	Disease	D007177
11195262	578	616	weakness of the central nervous system	Disease	D002493
11195262	653	656	VPA	Chemical	D014635
11195262	CID	D014635	D007177

10728962|t|Vasopressin in the treatment of milrinone-induced hypotension in severe heart failure.
10728962|a|The use of phosphodiesterase inhibitors such as milrinone in the treatment of severe heart failure is frequently restricted because they cause vasodilation and hypotension. In patients with decompensated heart failure with hypotension after treatment with milrinone, low doses of vasopressin restored blood pressure without inhibiting the inotropic effect of milrinone.
10728962	0	11	Vasopressin	Chemical	D014667
10728962	32	41	milrinone	Chemical	D020105
10728962	50	61	hypotension	Disease	D007022
10728962	72	85	heart failure	Disease	D006333
10728962	135	144	milrinone	Chemical	D020105
10728962	172	185	heart failure	Disease	D006333
10728962	247	258	hypotension	Disease	D007022
10728962	291	304	heart failure	Disease	D006333
10728962	310	321	hypotension	Disease	D007022
10728962	343	352	milrinone	Chemical	D020105
10728962	367	378	vasopressin	Chemical	D014667
10728962	446	455	milrinone	Chemical	D020105
10728962	CID	D014667	D007022
10728962	CID	D020105	D007022

7647582|t|Halogenated anesthetics form liver adducts and antigens that cross-react with halothane-induced antibodies.
7647582|a|Two halogenated anesthetics, enflurane and isoflurane, have been associated with an allergic-type hepatic injury both alone and following previous exposure to halothane. Halothane hepatitis appears to involve an aberrant immune response. An antibody response to a protein-bound biotransformation product (trifluoroacetyl adduct) has been detected on halothane hepatitis patients. This study was performed to determine cross-reactivity between enflurane and isoflurane with the hypersensitivity induced by halothane. The subcellular and lobular production of hepatic neoantigens recognized by halothane-induced antibodies following enflurane and isoflurane, and the biochemical nature of these neoantigens was investigated in two animal models. Enflurane administration resulted in neoantigens detected in both the microsomal and cytosolic fraction of liver homogenates and in the centrilobular region of the liver. In the same liver, biochemical analysis detected fluorinated liver adducts that were up to 20-fold greater in guinea pigs than in rats. This supports and extends previous evidence for a mechanism by which enflurane and/or isoflurane could produce a hypersensitivity condition similar to that of halothane hepatitis either alone or subsequent to halothane administration. The guinea pig would appear to be a useful model for further investigations of the immunological response to these antigens.
7647582	78	87	halothane	Chemical	D006221
7647582	137	146	enflurane	Chemical	D004737
7647582	151	161	isoflurane	Chemical	D007530
7647582	206	220	hepatic injury	Disease	D056486
7647582	267	276	halothane	Chemical	D006221
7647582	278	287	Halothane	Chemical	D006221
7647582	288	297	hepatitis	Disease	D056486
7647582	413	428	trifluoroacetyl	Chemical	D014269
7647582	458	467	halothane	Chemical	D006221
7647582	468	477	hepatitis	Disease	D056486
7647582	551	560	enflurane	Chemical	D004737
7647582	565	575	isoflurane	Chemical	D007530
7647582	585	601	hypersensitivity	Disease	D004342
7647582	613	622	halothane	Chemical	D006221
7647582	700	709	halothane	Chemical	D006221
7647582	739	748	enflurane	Chemical	D004737
7647582	753	763	isoflurane	Chemical	D007530
7647582	852	861	Enflurane	Chemical	D004737
7647582	1228	1237	enflurane	Chemical	D004737
7647582	1245	1255	isoflurane	Chemical	D007530
7647582	1272	1288	hypersensitivity	Disease	D004342
7647582	1318	1327	halothane	Chemical	D006221
7647582	1328	1337	hepatitis	Disease	D056486
7647582	1368	1377	halothane	Chemical	D006221
7647582	CID	D007530	D056486
7647582	CID	D004737	D056486
7647582	CID	D006221	D056486

4090988|t|Induction by paracetamol of bladder and liver tumours in the rat. Effects on hepatocyte fine structure.
4090988|a|Groups of male and female inbred Leeds strain rats were fed diets containing either 0.5% or 1.0% paracetamol by weight for up to 18 months. At the 1.0% dosage level, 20% of rats of both sexes developed neoplastic nodules of the liver, a statistically significant incidence. These rats also showed gross enlargement of their livers and an increase in foci of cellular alteration, the latter also being observed in the low dosage male rats. Papillomas of the transitional epithelium of the bladder developed in all paracetamol-treated groups, and three rats bore bladder carcinomas. However, significant yields of bladder tumours were only obtained from low dosage females and high dosage males. Additionally, 20 to 25% of paracetamol-treated rats developed hyperplasia of the bladder epithelium, which was not coincident with the presence of bladder calculi. A low yield of tumours at various other sites also arose following paracetamol feeding. An electron microscope study of the livers of paracetamol-treated rats revealed ultrastructural changes in the hepatocytes that resemble those that result from exposure to a variety of known hepatocarcinogens.
4090988	13	24	paracetamol	Chemical	D000082
4090988	28	53	bladder and liver tumours	Disease	D001749|D008113	bladder tumours|liver tumours
4090988	201	212	paracetamol	Chemical	D000082
4090988	543	553	Papillomas	Disease	D010212
4090988	617	628	paracetamol	Chemical	D000082
4090988	665	683	bladder carcinomas	Disease	D001749
4090988	716	731	bladder tumours	Disease	D001749
4090988	825	836	paracetamol	Chemical	D000082
4090988	860	871	hyperplasia	Disease	D006965
4090988	945	960	bladder calculi	Disease	D001744
4090988	977	984	tumours	Disease	D009369
4090988	1029	1040	paracetamol	Chemical	D000082
4090988	1096	1107	paracetamol	Chemical	D000082
4090988	1241	1258	hepatocarcinogens	Disease	D008113
4090988	CID	D000082	D006965
4090988	CID	D000082	D001749
4090988	CID	D000082	D008113

4038130|t|Rat extraocular muscle regeneration. Repair of local anesthetic-induced damage.
4038130|a|Local anesthetics that are commonly used in ophthalmic surgery (0.75% bupivacaine hydrochloride, 2.0% mepivacaine hydrochloride, and 2.0% lidocaine hydrochloride plus 1:100,000 epinephrine) were injected into the retrobulbar area of rat eyes. Controls were injected with physiological saline. All three anesthetics produced massive degeneration of the extraocular muscles. Muscle degeneration is followed by regeneration of the damaged muscle fibers. In addition to muscle damage, severe damage was also seen in harderian glands, especially after exposure to mepivacaine and lidocaine plus epinephrine. With these findings in rats, it is hypothesized that the temporary diplopia sometimes seen in patients after ophthalmic surgery might be due to anesthetic-induced damage to the extraocular muscles.
4038130	150	175	bupivacaine hydrochloride	Chemical	D002045
4038130	182	207	mepivacaine hydrochloride	Chemical	D008619
4038130	218	241	lidocaine hydrochloride	Chemical	D008012
4038130	257	268	epinephrine	Chemical	D004837
4038130	453	472	Muscle degeneration	Disease	D009135
4038130	546	559	muscle damage	Disease	D009135
4038130	639	650	mepivacaine	Chemical	D008619
4038130	655	664	lidocaine	Chemical	D008012
4038130	670	681	epinephrine	Chemical	D004837
4038130	750	758	diplopia	Disease	D004172
4038130	CID	D008012	D009135
4038130	CID	D008619	D009135
4038130	CID	D002045	D009135

2907585|t|Reversal of neuroleptic-induced catalepsy by novel aryl-piperazine anxiolytic drugs.
2907585|a|The novel anxiolytic drug, buspirone, reverses catalepsy induced by haloperidol. A series of aryl-piperazine analogues of buspirone and other 5-hydroxytryptaminergic agonists were tested for their ability to reverse haloperidol induced catalepsy. Those drugs with strong affinity for 5-hydroxytryptamine1a receptors were able to reverse catalepsy. Drugs with affinity for other 5-HT receptors or weak affinity were ineffective. However, inhibition of postsynaptic 5-HT receptors neither inhibited nor potentiated reversal of catalepsy and leaves open the question as to the site or mechanism for this effect.
2907585	32	41	catalepsy	Disease	D002375
2907585	51	66	aryl-piperazine	Chemical	-1
2907585	112	121	buspirone	Chemical	D002065
2907585	132	141	catalepsy	Disease	D002375
2907585	153	164	haloperidol	Chemical	D006220
2907585	178	193	aryl-piperazine	Chemical	-1
2907585	207	216	buspirone	Chemical	D002065
2907585	227	259	5-hydroxytryptaminergic agonists	Chemical	D058825
2907585	301	312	haloperidol	Chemical	D006220
2907585	321	330	catalepsy	Disease	D002375
2907585	369	388	5-hydroxytryptamine	Chemical	D012701
2907585	422	431	catalepsy	Disease	D002375
2907585	463	467	5-HT	Chemical	D012701
2907585	549	553	5-HT	Chemical	D012701
2907585	610	619	catalepsy	Disease	D002375
2907585	CID	D006220	D002375

2894433|t|Diazepam facilitates reflex bradycardia in conscious rats.
2894433|a|The effects of diazepam on cardiovascular function were assessed in conscious rats. Intravenous administration of diazepam (1-30 mg kg-1) produced a dose-dependent decrease in both the mean arterial pressure and the heart rate. Also, reflex bradycardia was produced in rats by intravenous infusion of adrenaline (1.25-2.5 micrograms kg-1). Intravenous pretreatment of the rats with diazepam, although causing no change in the adrenaline-induced pressor effect, did enhance the adrenaline-induced reflex bradycardia. However, the diazepam enhancement of adrenaline-induced reflex bradycardia was antagonized by pretreatment of rats with an intravenous dose of picrotoxin (an agent blocks chloride channels by binding to sites associated with the benzodiazepine-GABA-chloride channel macromolecular complex). The data indicate that diazepam acts through the benzodiazepine-GABA-chloride channel macromolecular complex within the central nervous system to facilitate reflex bradycardia mediated through baroreceptor reflexes in response to an acute increase in arterial pressure.
2894433	0	8	Diazepam	Chemical	D003975
2894433	28	39	bradycardia	Disease	D001919
2894433	74	82	diazepam	Chemical	D003975
2894433	173	181	diazepam	Chemical	D003975
2894433	300	311	bradycardia	Disease	D001919
2894433	360	370	adrenaline	Chemical	D004837
2894433	441	449	diazepam	Chemical	D003975
2894433	485	495	adrenaline	Chemical	D004837
2894433	536	546	adrenaline	Chemical	D004837
2894433	562	573	bradycardia	Disease	D001919
2894433	588	596	diazepam	Chemical	D003975
2894433	612	622	adrenaline	Chemical	D004837
2894433	638	649	bradycardia	Disease	D001919
2894433	718	728	picrotoxin	Chemical	D010852
2894433	746	754	chloride	Chemical	D002712
2894433	804	818	benzodiazepine	Chemical	D001569
2894433	819	823	GABA	Chemical	D005680
2894433	824	832	chloride	Chemical	D002712
2894433	889	897	diazepam	Chemical	D003975
2894433	915	929	benzodiazepine	Chemical	D001569
2894433	930	934	GABA	Chemical	D005680
2894433	935	943	chloride	Chemical	D002712
2894433	1030	1041	bradycardia	Disease	D001919
2894433	CID	D004837	D001919
2894433	CID	D003975	D001919

2790457|t|Chronic carbamazepine inhibits the development of local anesthetic seizures kindled by cocaine and lidocaine.
2790457|a|The effects of carbamazepine (CBZ) treatment on local anesthetic-kindled seizures and lethality were evaluated in different stages of the kindling process and under different methods of CBZ administration. Chronic oral CBZ inhibited the development of both lidocaine- and cocaine-induced seizures, but had little effect on the fully developed local anesthetic seizures. Chronic CBZ also decreased the incidence of seizure-related mortality in the cocaine-injected rats. Acute CBZ over a range of doses (15-50 mg/kg) had no effect on completed lidocaine-kindled or acute cocaine-induced seizures. Repeated i.p. injection of CBZ (15 mg/kg) also was without effect on the development of lidocaine- or cocaine-kindled seizures. The differential effects of CBZ depending upon stage of seizure development suggest that distinct mechanisms underlie the development versus maintenance of local anesthetic-kindled seizures. The effectiveness of chronic but not repeated, intermittent injections of CBZ suggests that different biochemical consequences result from the different treatment regimens. The possible utility of chronic CBZ in preventing the development of toxic side effects in human cocaine users is suggested by these data, but remains to be directly evaluated.
2790457	8	21	carbamazepine	Chemical	D002220
2790457	67	75	seizures	Disease	D012640
2790457	87	94	cocaine	Chemical	D003042
2790457	99	108	lidocaine	Chemical	D008012
2790457	125	138	carbamazepine	Chemical	D002220
2790457	140	143	CBZ	Chemical	D002220
2790457	183	191	seizures	Disease	D012640
2790457	296	299	CBZ	Chemical	D002220
2790457	329	332	CBZ	Chemical	D002220
2790457	367	376	lidocaine	Chemical	D008012
2790457	382	389	cocaine	Chemical	D003042
2790457	398	406	seizures	Disease	D012640
2790457	470	478	seizures	Disease	D012640
2790457	488	491	CBZ	Chemical	D002220
2790457	524	531	seizure	Disease	D012640
2790457	557	564	cocaine	Chemical	D003042
2790457	586	589	CBZ	Chemical	D002220
2790457	653	662	lidocaine	Chemical	D008012
2790457	680	687	cocaine	Chemical	D003042
2790457	696	704	seizures	Disease	D012640
2790457	733	736	CBZ	Chemical	D002220
2790457	794	803	lidocaine	Chemical	D008012
2790457	808	815	cocaine	Chemical	D003042
2790457	824	832	seizures	Disease	D012640
2790457	862	865	CBZ	Chemical	D002220
2790457	890	897	seizure	Disease	D012640
2790457	1015	1023	seizures	Disease	D012640
2790457	1099	1102	CBZ	Chemical	D002220
2790457	1230	1233	CBZ	Chemical	D002220
2790457	1295	1302	cocaine	Chemical	D003042
2790457	CID	D008012	D012640
2790457	CID	D003042	D012640

2334179|t|D-penicillamine in the treatment of localized scleroderma.
2334179|a|Localized scleroderma has no recognized internal organ involvement but may be disfiguring and disabling when the cutaneous lesions are extensive or affect children. There is no accepted or proven treatment for localized scleroderma. Case reports of 11 patients with severe, extensive localized scleroderma who were treated with D-penicillamine are summarized in this article. This drug was judged to have a favorable effect on the disease course in 7 (64%) of 11 patients. Improvement began within 3 to 6 months and consisted of cessation of active cutaneous lesions in all 7 patients, skin softening in 5, and more normal growth of the affected limb in 2 of 3 children. Joint stiffness and contractures also improved. The dose of D-penicillamine associated with a favorable response was as low as 2 to 5 mg/kg per day given over a period ranging from 15 to 53 months. D-Penicillamine caused nephrotic syndrome in 1 patient and milder reversible proteinuria in 3 other patients; none developed renal insufficiency. These data suggest that D-penicillamine may be effective in severe cases of localized scleroderma.
2334179	0	15	D-penicillamine	Chemical	D010396
2334179	36	57	localized scleroderma	Disease	D012594
2334179	59	80	Localized scleroderma	Disease	D012594
2334179	269	290	localized scleroderma	Disease	D012594
2334179	343	364	localized scleroderma	Disease	D012594
2334179	387	402	D-penicillamine	Chemical	D010396
2334179	750	762	contractures	Disease	D003286
2334179	790	805	D-penicillamine	Chemical	D010396
2334179	928	943	D-Penicillamine	Chemical	D010396
2334179	951	969	nephrotic syndrome	Disease	D009404
2334179	1005	1016	proteinuria	Disease	D011507
2334179	1053	1072	renal insufficiency	Disease	D051437
2334179	1098	1113	D-penicillamine	Chemical	D010396
2334179	1150	1171	localized scleroderma	Disease	D012594
2334179	CID	D010396	D009404
2334179	CID	D010396	D011507

1969772|t|Preservation of renal blood flow during hypotension induced with fenoldopam in dogs.
1969772|a|The introduction of drugs that could induce hypotension with different pharmacological actions would be advantageous because side effects unique to a specific drug could be minimized by selecting appropriate therapy. Specific dopamine-1, (DA1) and dopamine-2 (DA2) receptor agonists are now under clinical investigation. Fenoldopam mesylate is a specific DA1 receptor agonist that lowers blood pressure by vasodilatation. The hypothesis that fenoldopam could be used to induce hypotension and preserve blood flow to the kidney was tested. Systemic aortic blood pressure and renal blood flow were measured continuously with a carotid arterial catheter and an electromagnetic flow probe respectively, in order to compare the cardiovascular and renal vascular effects of fenoldopam and sodium nitroprusside in ten dogs under halothane general anaesthesia. Mean arterial pressure was decreased 30 +/- 8 per cent from control with infusion of fenoldopam (3.4 +/- 2.0 micrograms.kg-1.min-1) and 34 +/- 4 per cent with infusion of sodium nitroprusside (5.9 micrograms.kg-1.min-1) (NS). Renal blood flow (RBF) increased during fenoldopam-induced hypotension 11 +/- 7 per cent and decreased 21 +/- 8 per cent during sodium nitroprusside-induced hypotension (P less than 0.01). Sodium nitroprusside is a non-selective arteriolar and venous vasodilator that can produce redistribution of blood flow away from the kidney during induced hypotension. Fenoldopam is a selective dopamine-1 (DA1) receptor agonist that causes vasodilatation to the kidney and other organs with DA1 receptors and preserves blood flow to the kidney during induced hypotension.
1969772	40	51	hypotension	Disease	D007022
1969772	65	75	fenoldopam	Chemical	D018818
1969772	129	140	hypotension	Disease	D007022
1969772	311	319	dopamine	Chemical	D004298
1969772	324	326	DA	Chemical	D004298
1969772	333	341	dopamine	Chemical	D004298
1969772	345	347	DA	Chemical	D004298
1969772	406	425	Fenoldopam mesylate	Chemical	D018818
1969772	527	537	fenoldopam	Chemical	D018818
1969772	562	573	hypotension	Disease	D007022
1969772	853	863	fenoldopam	Chemical	D018818
1969772	868	874	sodium	Chemical	D012964
1969772	875	888	nitroprusside	Chemical	D009599
1969772	907	916	halothane	Chemical	D006221
1969772	1023	1033	fenoldopam	Chemical	D018818
1969772	1109	1115	sodium	Chemical	D012964
1969772	1116	1129	nitroprusside	Chemical	D009599
1969772	1204	1214	fenoldopam	Chemical	D018818
1969772	1223	1234	hypotension	Disease	D007022
1969772	1292	1298	sodium	Chemical	D012964
1969772	1299	1312	nitroprusside	Chemical	D009599
1969772	1321	1332	hypotension	Disease	D007022
1969772	1360	1373	nitroprusside	Chemical	D009599
1969772	1509	1520	hypotension	Disease	D007022
1969772	1548	1556	dopamine	Chemical	D004298
1969772	1713	1724	hypotension	Disease	D007022
1969772	CID	D018818	D007022
1969772	CID	D009599	D007022
1969772	CID	D006221	D007022

1700207|t|Antiarrhythmic effects of optical isomers of cibenzoline on canine ventricular arrhythmias.
1700207|a|Antiarrhythmic effects of (+)-cibenzoline and (-)-cibenzoline were examined using two canine ventricular arrhythmia models. Digitalis arrhythmia, which is suppressed by Na channel blockers, was induced by intermittent intravenous (i.v.) injection of ouabain in pentobarbital-anesthetized dogs. Adrenaline arrhythmia, which is suppressed by Ca channel blockers, was induced by adrenaline infusion in halothane-anesthetized dogs. Ten and 5 mg/kg i.v. (+)-cibenzoline suppressed digitalis- and adrenaline-induced arrhythmias, respectively. The minimum effective plasma concentrations of (+)-cibenzoline for digitalis- and adrenaline-induced arrhythmias were 1.4 +/- 0.4 and 2.0 +/- 0.6 micrograms/ml, respectively (mean +/- SD, n = 6). A lower dose of 1 mg/kg i.v. of (-)-cibenzoline suppressed the digitalis-induced arrhythmia, whereas 5 mg/kg i.v. was needed to suppress adrenaline-induced arrhythmias. The minimum effective plasma concentrations of (-)-cibenzoline for digitalis- and adrenaline-induced arrhythmia were 0.06 +/- 0.04 and 0.7 +/- 0.1 micrograms/ml, respectively (mean +/- SD, n = 6). The stronger antiarrhythmic effect of (-)-cibenzoline indicates that (-)-isomer may have an effect nearly 5-20 times stronger in suppressing Na channels, but effects of both drugs on Ca channels may be almost equipotent.
1700207	45	56	cibenzoline	Chemical	C032151
1700207	67	90	ventricular arrhythmias	Disease	D001145
1700207	122	133	cibenzoline	Chemical	C032151
1700207	142	153	cibenzoline	Chemical	C032151
1700207	185	207	ventricular arrhythmia	Disease	D001145
1700207	216	225	Digitalis	Chemical	D004070
1700207	226	236	arrhythmia	Disease	D001145
1700207	261	263	Na	Chemical	D012964
1700207	342	349	ouabain	Chemical	D010042
1700207	353	366	pentobarbital	Chemical	D010424
1700207	386	407	Adrenaline arrhythmia	Disease	D001145
1700207	432	434	Ca	Chemical	D002118
1700207	468	478	adrenaline	Chemical	D004837
1700207	491	500	halothane	Chemical	D006221
1700207	545	556	cibenzoline	Chemical	C032151
1700207	568	577	digitalis	Chemical	D004070
1700207	583	593	adrenaline	Chemical	D004837
1700207	602	613	arrhythmias	Disease	D001145
1700207	680	691	cibenzoline	Chemical	C032151
1700207	696	705	digitalis	Chemical	D004070
1700207	711	721	adrenaline	Chemical	D004837
1700207	730	741	arrhythmias	Disease	D001145
1700207	861	872	cibenzoline	Chemical	C032151
1700207	888	897	digitalis	Chemical	D004070
1700207	906	916	arrhythmia	Disease	D001145
1700207	962	972	adrenaline	Chemical	D004837
1700207	981	992	arrhythmias	Disease	D001145
1700207	1045	1056	cibenzoline	Chemical	C032151
1700207	1061	1070	digitalis	Chemical	D004070
1700207	1076	1086	adrenaline	Chemical	D004837
1700207	1095	1105	arrhythmia	Disease	D001145
1700207	1233	1244	cibenzoline	Chemical	C032151
1700207	1332	1334	Na	Chemical	D012964
1700207	1374	1376	Ca	Chemical	D002118
1700207	CID	D004837	D001145
1700207	CID	D010042	D001145

19761039|t|Effect of Hibiscus rosa sinensis on reserpine-induced neurobehavioral and biochemical alterations in rats.
19761039|a|Effect of methanolic extract of Hibiscus rosa sinensis (100-300 mg/kg) was studied on reserpine-induced orofacial dyskinesia and neurochemical alterations. The rats were treated with intraperitoneal reserpine (1 mg/kg, ip) for 3 days every other day. On day 5, vacuous chewing movements and tongue protrusions were counted for 5 min. Reserpine treated rats significantly developed vacuous chewing movements and tongue protrusions however, coadministration of Hibiscus rosa sinensis roots extract (100, 200 and 300 mg/kg, per orally) attenuated the effects. Biochemical analysis of brain revealed that the reserpine treatment significantly increased lipid peroxidation and decreased levels of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GSH), an index of oxidative stress process. Coadministration of extract significantly reduced the lipid peroxidation and reversed the decrease in brain SOD, CAT and GSH levels. The results of the present study suggested that Hibiscus rosa sinensis had a protective role against reserpine-induced orofacial dyskinesia and oxidative stress.
19761039	10	32	Hibiscus rosa sinensis	Chemical	D010936
19761039	36	45	reserpine	Chemical	D012110
19761039	139	161	Hibiscus rosa sinensis	Chemical	D010936
19761039	193	202	reserpine	Chemical	D012110
19761039	221	231	dyskinesia	Disease	D004409
19761039	306	315	reserpine	Chemical	D012110
19761039	441	450	Reserpine	Chemical	D012110
19761039	566	588	Hibiscus rosa sinensis	Chemical	D010936
19761039	712	721	reserpine	Chemical	D012110
19761039	799	809	superoxide	Chemical	D013481
19761039	846	857	glutathione	Chemical	D005978
19761039	1094	1116	Hibiscus rosa sinensis	Chemical	D010936
19761039	1147	1156	reserpine	Chemical	D012110
19761039	1175	1185	dyskinesia	Disease	D004409
19761039	CID	D012110	D004409

11704023|t|Comparison of aqueous and gellan ophthalmic timolol with placebo on the 24-hour heart rate response in patients on treatment for glaucoma.
11704023|a|PURPOSE: Topical beta-blocker treatment is routine therapy in the management of patients with glaucoma. Therapy results in systemic absorption, however, the degree of reduction of resting and peak heart rate has not been quantified. DESIGN: This trial evaluated the effect of placebo, 0.5% aqueous timolol (timolol solution) and a 0.5% timolol suspension that forms a gel on application to the conjunctiva (timolol gellan) on the 24-hour heart rate in patients currently being treated for glaucoma to quantify the reduction in mean heart rate. METHODS: Forty-three Caucasian patients with primary open-angle glaucoma or ocular hypertension with a mean (+/-SD) age of 63 (+/-8) years were randomized and crossed over in a double-masked manner to 14 days of treatment with placebo (morning and evening in both eyes), timolol solution (morning and evening in both eyes), or timolol gellan (morning in both eyes with placebo in the evening). On the 13th day of each period, heart rate was recorded continuously during a typical, ambulant 24-hour period. RESULTS: Both timolol solution and timolol gellan reduced the mean 24-hour heart rate compared with placebo (P < or = .001), and this reduction was most pronounced during the daytime (-7.5% change in mean heart rate, -5.7 beats/min). Timolol gellan showed a numerically but not significantly smaller reduction in 24-hour heart rate, compared with timolol solution. During the night, the mean 12-hour heart rate on placebo and timolol gellan were both significantly less than on timolol solution; the difference between solution and gellan treatments was statistically significant (P = .01). CONCLUSIONS: Both timolol solution and timolol gellan decrease the mean 24-hour heart rate compared with placebo. This response was most pronounced during the active daytime period. These data quantify the modest bradycardia associated with ophthalmic beta-blocker therapy in a typical patient population on therapy for glaucoma. Although exercise performance was not assessed in this trial, reductions of this magnitude should not have substantial clinical consequences.
11704023	44	51	timolol	Chemical	D013999
11704023	129	137	glaucoma	Disease	D005901
11704023	233	241	glaucoma	Disease	D005901
11704023	437	444	timolol	Chemical	D013999
11704023	446	453	timolol	Chemical	D013999
11704023	475	482	timolol	Chemical	D013999
11704023	546	553	timolol	Chemical	D013999
11704023	628	636	glaucoma	Disease	D005901
11704023	736	755	open-angle glaucoma	Disease	D005902
11704023	759	778	ocular hypertension	Disease	D009798
11704023	954	961	timolol	Chemical	D013999
11704023	1010	1017	timolol	Chemical	D013999
11704023	1203	1210	timolol	Chemical	D013999
11704023	1224	1231	timolol	Chemical	D013999
11704023	1423	1430	Timolol	Chemical	D013999
11704023	1536	1543	timolol	Chemical	D013999
11704023	1615	1622	timolol	Chemical	D013999
11704023	1667	1674	timolol	Chemical	D013999
11704023	1798	1805	timolol	Chemical	D013999
11704023	1819	1826	timolol	Chemical	D013999
11704023	1993	2004	bradycardia	Disease	D001919
11704023	2100	2108	glaucoma	Disease	D005901
11704023	CID	D013999	D001919

19300240|t|5 flourouracil-induced apical ballooning syndrome: a case report.
19300240|a|The apical ballooning syndrome (ABS) is a recently described stress-mediated acute cardiac syndrome characterized by transient wall-motion abnormalities involving the apex and midventricle with hyperkinesis of the basal left ventricular (LV) segments without obstructive epicardial coronary disease. Cardiotoxicity is not an uncommon adverse effect of chemotherapeutic agents. However, there are no reports of ABS secondary to chemotherapeutic agents. We describe the case of a woman who developed the syndrome after chemotherapy for metastatic cancer. A 79-year-old woman presented with typical ischemic chest pain, elevated cardiac enzymes with significant ST-segment abnormalities on her electrocardiogram. She underwent recent chemotherapy with fluorouracil for metastatic colorectal cancer. Echocardiography revealed a wall-motion abnormality involving the apical and periapical segments which appeared akinetic. Coronary angiography revealed no obstructive coronary lesions. The patient was stabilized with medical therapy. Four weeks later she remained completely asymptomatic. Echocardiogram revealed a normal ejection fraction and a resolution of the apical akinesis. Pathogenetic mechanisms of cardiac complications in cancer patients undergoing chemotherapy include coronary vasospasm, endothelial damage and consequent thrombus formation. In our patient, both supraphysiologic levels of plasma catecholamines and stress related neuropeptides caused by cancer diagnosis as well as chemotherapy may have contributed the development of ABS.
19300240	0	14	5 flourouracil	Chemical	D005472
19300240	23	49	apical ballooning syndrome	Disease	D054549
19300240	70	96	apical ballooning syndrome	Disease	D054549
19300240	98	101	ABS	Disease	D054549
19300240	143	165	acute cardiac syndrome	Disease	D006331
19300240	260	272	hyperkinesis	Disease	D006948
19300240	337	364	epicardial coronary disease	Disease	D003327
19300240	366	380	Cardiotoxicity	Disease	D066126
19300240	476	479	ABS	Disease	D054549
19300240	611	617	cancer	Disease	D009369
19300240	662	670	ischemic	Disease	D007511
19300240	671	681	chest pain	Disease	D002637
19300240	815	827	fluorouracil	Chemical	D005472
19300240	843	860	colorectal cancer	Disease	D015179
19300240	974	982	akinetic	Disease	D018476
19300240	1233	1241	akinesis	Disease	D018476
19300240	1270	1291	cardiac complications	Disease	D005117
19300240	1295	1301	cancer	Disease	D009369
19300240	1343	1361	coronary vasospasm	Disease	D003329
19300240	1397	1405	thrombus	Disease	D013927
19300240	1472	1486	catecholamines	Chemical	D002395
19300240	1530	1536	cancer	Disease	D009369
19300240	1611	1614	ABS	Disease	D054549
19300240	CID	D005472	D054549
19300240	CID	D005472	D002637

18006530|t|Reduction of pain during induction with target-controlled propofol and remifentanil.
18006530|a|BACKGROUND: Pain on injection of propofol is unpleasant. We hypothesized that propofol infusion pain might be prevented by infusing remifentanil before starting the propofol infusion in a clinical setting where target-controlled infusions (TCI) of both drugs were used. A prospective, randomized, double-blind, placebo-controlled trial was performed to determine the effect-site concentration (Ce) of remifentanil to prevent the pain without producing complications. METHODS: A total of 128 patients undergoing general surgery were randomly allocated to receive normal saline (control) or remifentanil to a target Ce of 2 ng ml(-1) (R2), 4 ng ml(-1) (R4), or 6 ng ml(-1) (R6) administered via TCI. After the target Ce was achieved, the infusion of propofol was started. Remifentanil-related complications were assessed during the remifentanil infusion, and pain caused by propofol was evaluated using a four-point scale during the propofol infusion. RESULTS: The incidence of pain was significantly lower in Groups R4 and R6 than in the control and R2 groups (12/32 and 6/31 vs 26/31 and 25/32, respectively, P<0.001). Pain was less severe in Groups R4 and R6 than in the control and R2 groups (P<0.001). However, both incidence and severity of pain were not different between Groups R4 and R6. No significant complications were observed during the study. CONCLUSIONS: During induction of anaesthesia with TCI of propofol and remifentanil, a significant reduction in propofol infusion pain was achieved without significant complications by prior administration of remifentanil at a target Ce of 4 ng ml(-1).
18006530	13	17	pain	Disease	D010146
18006530	58	66	propofol	Chemical	D015742
18006530	71	83	remifentanil	Chemical	C071741
18006530	97	101	Pain	Disease	D010146
18006530	118	126	propofol	Chemical	D015742
18006530	163	171	propofol	Chemical	D015742
18006530	181	185	pain	Disease	D010146
18006530	217	229	remifentanil	Chemical	C071741
18006530	250	258	propofol	Chemical	D015742
18006530	486	498	remifentanil	Chemical	C071741
18006530	514	518	pain	Disease	D010146
18006530	674	686	remifentanil	Chemical	C071741
18006530	833	841	propofol	Chemical	D015742
18006530	855	867	Remifentanil	Chemical	C071741
18006530	915	927	remifentanil	Chemical	C071741
18006530	942	946	pain	Disease	D010146
18006530	957	965	propofol	Chemical	D015742
18006530	1016	1024	propofol	Chemical	D015742
18006530	1061	1065	pain	Disease	D010146
18006530	1204	1208	Pain	Disease	D010146
18006530	1330	1334	pain	Disease	D010146
18006530	1498	1506	propofol	Chemical	D015742
18006530	1511	1523	remifentanil	Chemical	C071741
18006530	1552	1560	propofol	Chemical	D015742
18006530	1570	1574	pain	Disease	D010146
18006530	1649	1661	remifentanil	Chemical	C071741
18006530	CID	D015742	D010146

17702969|t|Prenatal exposure to fluoxetine induces fetal pulmonary hypertension in the rat.
17702969|a|RATIONALE: Fluoxetine is a selective serotonin reuptake inhibitor antidepressant widely used by pregnant women. Epidemiological data suggest that fluoxetine exposure prenatally increases the prevalence of persistent pulmonary hypertension syndrome of the newborn. The mechanism responsible for this effect is unclear and paradoxical, considering the current evidence of a pulmonary hypertension protective fluoxetine effect in adult rodents. OBJECTIVES: To evaluate the fluoxetine effect on fetal rat pulmonary vascular smooth muscle mechanical properties and cell proliferation rate. METHODS: Pregnant rats were treated with fluoxetine (10 mg/kg) from Day 11 through Day 21 of gestation. MEASUREMENTS AND MAIN RESULTS: Fetuses were delivered by cesarean section. As compared with controls, fluoxetine exposure resulted in fetal pulmonary hypertension as evidenced by an increase in the weight ratio of the right ventricle to the left ventricle plus septum (P = 0.02) and by an increase in pulmonary arterial medial thickness (P < 0.01). Postnatal mortality was increased among experimental animals, and arterial oxygen saturation was 96 +/- 1% in 1-day-old control animals and significantly lower (P < 0.01) in fluoxetine-exposed pups (79 +/- 2%). In vitro, fluoxetine induced pulmonary arterial muscle contraction in fetal, but not adult, animals (P < 0.01) and reduced serotonin-induced contraction at both ages (P < 0.01). After in utero exposure to a low fluoxetine concentration the pulmonary arterial smooth muscle cell proliferation rate was significantly increased in fetal, but not adult, cells (P < 0.01). CONCLUSIONS: In contrast to the adult, fluoxetine exposure in utero induces pulmonary hypertension in the fetal rat as a result of a developmentally regulated increase in pulmonary vascular smooth muscle proliferation.
17702969	21	31	fluoxetine	Chemical	D005473
17702969	40	68	fetal pulmonary hypertension	Disease	D005315|D006976	fetal pulmonary hypertension|pulmonary hypertension
17702969	92	102	Fluoxetine	Chemical	D005473
17702969	118	127	serotonin	Chemical	D012701
17702969	227	237	fluoxetine	Chemical	D005473
17702969	297	328	pulmonary hypertension syndrome	Disease	D006976
17702969	453	475	pulmonary hypertension	Disease	D006976
17702969	487	497	fluoxetine	Chemical	D005473
17702969	551	561	fluoxetine	Chemical	D005473
17702969	707	717	fluoxetine	Chemical	D005473
17702969	872	882	fluoxetine	Chemical	D005473
17702969	904	932	fetal pulmonary hypertension	Disease	D005315|D006976	fetal pulmonary hypertension|pulmonary hypertension
17702969	1194	1200	oxygen	Chemical	D010100
17702969	1293	1303	fluoxetine	Chemical	D005473
17702969	1340	1350	fluoxetine	Chemical	D005473
17702969	1453	1462	serotonin	Chemical	D012701
17702969	1541	1551	fluoxetine	Chemical	D005473
17702969	1737	1747	fluoxetine	Chemical	D005473
17702969	1774	1796	pulmonary hypertension	Disease	D006976
17702969	CID	D005473	D005315
17702969	CID	D005473	D006976

17344330|t|Syncope and QT prolongation among patients treated with methadone for heroin dependence in the city of Copenhagen.
17344330|a|BACKGROUND: Methadone is prescribed to heroin addicts to decrease illicit opioid use. Prolongation of the QT interval in the ECG of patients with torsade de pointes (TdP) has been reported in methadone users. As heroin addicts sometimes faint while using illicit drugs, doctors might attribute too many episodes of syncope to illicit drug use and thereby underestimate the incidence of TdP in this special population, and the high mortality in this population may, in part, be caused by the proarrhythmic effect of methadone. METHODS: In this cross-sectional study interview, ECGs and blood samples were collected in a population of adult heroin addicts treated with methadone or buprenorphine on a daily basis. Of the patients at the Drug Addiction Service in the municipal of Copenhagen, 450 (approximately 52%) were included. The QT interval was estimated from 12 lead ECGs. All participants were interviewed about any experience of syncope. The association between opioid dose and QT, and methadone dose and reporting of syncope was assessed using multivariate linear regression and logistic regression, respectively. RESULTS: Methadone dose was associated with longer QT interval of 0.140 ms/mg (p = 0.002). No association between buprenorphine and QTc was found. Among the subjects treated with methadone, 28% men and 32% women had prolonged QTc interval. None of the subjects treated with buprenorphine had QTc interval >0.440 s((1/2)). A 50 mg higher methadone dose was associated with a 1.2 (95% CI 1.1 to 1.4) times higher odds for syncope. CONCLUSIONS: Methadone is associated with QT prolongation and higher reporting of syncope in a population of heroin addicts.
17344330	0	7	Syncope	Disease	D013575
17344330	12	27	QT prolongation	Disease	D008133
17344330	56	65	methadone	Chemical	D008691
17344330	70	76	heroin	Chemical	D003932
17344330	127	136	Methadone	Chemical	D008691
17344330	154	160	heroin	Chemical	D003932
17344330	261	279	torsade de pointes	Disease	D016171
17344330	281	284	TdP	Disease	D016171
17344330	307	316	methadone	Chemical	D008691
17344330	327	333	heroin	Chemical	D003932
17344330	430	437	syncope	Disease	D013575
17344330	501	504	TdP	Disease	D016171
17344330	630	639	methadone	Chemical	D008691
17344330	754	760	heroin	Chemical	D003932
17344330	782	791	methadone	Chemical	D008691
17344330	795	808	buprenorphine	Chemical	D002047
17344330	1051	1058	syncope	Disease	D013575
17344330	1108	1117	methadone	Chemical	D008691
17344330	1140	1147	syncope	Disease	D013575
17344330	1246	1255	Methadone	Chemical	D008691
17344330	1351	1364	buprenorphine	Chemical	D002047
17344330	1416	1425	methadone	Chemical	D008691
17344330	1453	1475	prolonged QTc interval	Disease	D008133
17344330	1511	1524	buprenorphine	Chemical	D002047
17344330	1574	1583	methadone	Chemical	D008691
17344330	1657	1664	syncope	Disease	D013575
17344330	1679	1688	Methadone	Chemical	D008691
17344330	1708	1723	QT prolongation	Disease	D008133
17344330	1748	1755	syncope	Disease	D013575
17344330	1775	1781	heroin	Chemical	D003932
17344330	CID	D008691	D008133
17344330	CID	D008691	D013575

16826348|t|Peripheral neuropathy caused by high-dose cytosine arabinoside treatment in a patient with acute myeloid leukemia.
16826348|a|The central nervous system toxicity of high-dose cytosine arabinoside is well recognized, but the toxicity of cytosine arabinoside in the peripheral nervous system has been infrequently reported. A 49-year-old Japanese man was diagnosed with acute myeloid leukemia. After he achieved complete remission, he received high-dose cytosine arabinoside treatment (2 g/m2 twice a day for 5 days; total, 20 g/m2) as consolidation therapy. The first course of high-dose cytosine arabinoside resulted in no unusual symptoms, but on day 21 of the second course of treatment, the patient complained of numbness in his right foot. Electromyogram and nerve-conduction studies showed peripheral neuropathy in both peroneal nerves. This neuropathy was gradually resolving; however, after the patient received allogeneic bone marrow transplantation, the symptoms worsened, with the development of graft-versus-host disease, and the symptoms subsequently responded to methylprednisolone. Although the mechanisms of peripheral neuropathy are still unclear, high-dose cytosine arabinoside is a therapy that is potentially toxic to the peripheral nervous system, and auto/alloimmunity may play an important role in these mechanisms.
16826348	0	21	Peripheral neuropathy	Disease	D010523
16826348	42	62	cytosine arabinoside	Chemical	D003561
16826348	91	113	acute myeloid leukemia	Disease	D015470
16826348	142	150	toxicity	Disease	D064420
16826348	164	184	cytosine arabinoside	Chemical	D003561
16826348	213	221	toxicity	Disease	D064420
16826348	225	245	cytosine arabinoside	Chemical	D003561
16826348	357	379	acute myeloid leukemia	Disease	D015470
16826348	441	461	cytosine arabinoside	Chemical	D003561
16826348	576	596	cytosine arabinoside	Chemical	D003561
16826348	705	713	numbness	Disease	D006987
16826348	784	805	peripheral neuropathy	Disease	D010523
16826348	836	846	neuropathy	Disease	D009422
16826348	995	1020	graft-versus-host disease	Disease	D006086
16826348	1065	1083	methylprednisolone	Chemical	D008775
16826348	1112	1133	peripheral neuropathy	Disease	D010523
16826348	1163	1183	cytosine arabinoside	Chemical	D003561
16826348	CID	D003561	D010523

16820346|t|Atorvastatin prevented and reversed dexamethasone-induced hypertension in the rat.
16820346|a|To assess the antioxidant effects of atorvastatin (atorva) on dexamethasone (dex)-induced hypertension, 60 male Sprague-Dawley rats were treated with atorva 30 mg/kg/day or tap water for 15 days. Dex increased systolic blood pressure (SBP) from 109 +/- 1.8 to 135 +/- 0.6 mmHg and plasma superoxide (5711 +/- 284.9 saline, 7931 +/- 392.8 U/ml dex, P < 0.001). In this prevention study, SBP in the atorva + dex group was increased from 115 +/- 0.4 to 124 +/- 1.5 mmHg, but this was significantly lower than in the dex-only group (P' < 0.05). Atorva reversed dex-induced hypertension (129 +/- 0.6 mmHg, vs. 135 +/- 0.6 mmHg P' < 0.05) and decreased plasma superoxide (7931 +/- 392.8 dex, 1187 +/- 441.2 atorva + dex, P < 0.0001). Plasma nitrate/nitrite (NOx) was decreased in dex-treated rats compared to saline-treated rats (11.2 +/- 1.08 microm, 15.3 +/- 1.17 microm, respectively, P < 0.05). Atorva affected neither plasma NOx nor thymus weight. Thus, atorvastatin prevented and reversed dexamethasone-induced hypertension in the rat.
16820346	0	12	Atorvastatin	Chemical	C065179
16820346	36	49	dexamethasone	Chemical	D003907
16820346	58	70	hypertension	Disease	D006973
16820346	120	132	atorvastatin	Chemical	C065179
16820346	134	140	atorva	Chemical	C065179
16820346	145	158	dexamethasone	Chemical	D003907
16820346	160	163	dex	Chemical	D003907
16820346	173	185	hypertension	Disease	D006973
16820346	233	239	atorva	Chemical	C065179
16820346	279	282	Dex	Chemical	D003907
16820346	371	381	superoxide	Chemical	D013481
16820346	426	429	dex	Chemical	D003907
16820346	480	486	atorva	Chemical	C065179
16820346	489	492	dex	Chemical	D003907
16820346	596	599	dex	Chemical	D003907
16820346	624	630	Atorva	Chemical	C065179
16820346	640	643	dex	Chemical	D003907
16820346	652	664	hypertension	Disease	D006973
16820346	737	747	superoxide	Chemical	D013481
16820346	764	767	dex	Chemical	D003907
16820346	784	790	atorva	Chemical	C065179
16820346	793	796	dex	Chemical	D003907
16820346	818	825	nitrate	Chemical	D009566
16820346	826	833	nitrite	Chemical	D009573
16820346	857	860	dex	Chemical	D003907
16820346	976	982	Atorva	Chemical	C065179
16820346	1036	1048	atorvastatin	Chemical	C065179
16820346	1072	1085	dexamethasone	Chemical	D003907
16820346	1094	1106	hypertension	Disease	D006973
16820346	CID	D003907	D006973

15974569|t|Two prodrugs of potent and selective GluR5 kainate receptor antagonists actives in three animal models of pain.
15974569|a|Amino acids 5 and 7, two potent and selective competitive GluR5 KA receptor antagonists, exhibited high GluR5 receptor affinity over other glutamate receptors. Their ester prodrugs 6 and 8 were orally active in three models of pain: reversal of formalin-induced paw licking, carrageenan-induced thermal hyperalgesia, and capsaicin-induced mechanical hyperalgesia.
15974569	43	50	kainate	Chemical	D007608
15974569	106	110	pain	Disease	D010146
15974569	176	178	KA	Chemical	D007608
15974569	251	260	glutamate	Chemical	D018698
15974569	339	343	pain	Disease	D010146
15974569	357	365	formalin	Chemical	D005557
15974569	387	398	carrageenan	Chemical	D002351
15974569	407	427	thermal hyperalgesia	Disease	D006930
15974569	433	442	capsaicin	Chemical	D002211
15974569	451	474	mechanical hyperalgesia	Disease	D006930
15974569	CID	D002351	D006930
15974569	CID	D002211	D006930

11583940|t|Sirolimus and mycophenolate mofetil for calcineurin-free immunosuppression in renal transplant recipients.
11583940|a|Calcineurin inhibitors, such as cyclosporine and tacrolimus, have been available for almost 20 years. Although these drugs are highly effective and represent the mainstay of transplant immunosuppression, they are associated with acute and chronic nephrotoxicity. Acute nephrotoxicity, which occurs in the early period after transplantation, leads to a higher rate of dialysis, and chronic nephrotoxicity may eventually result in graft loss. Acute and chronic nephrotoxicity is becoming more common as the use of marginal kidneys for transplantation increases. Two recently available immunosuppressive agents, mycophenolate mofetil and sirolimus (rapamycin), have no nephrotoxicity. The use of these drugs in combination with other agents has led to the development of new paradigms of immunosuppressive therapy. This paper reviews the results of clinical trials that have investigated these new approaches to immunosuppression in renal transplant recipients.
11583940	0	9	Sirolimus	Chemical	D020123
11583940	14	35	mycophenolate mofetil	Chemical	C063008
11583940	139	151	cyclosporine	Chemical	D016572
11583940	156	166	tacrolimus	Chemical	D016559
11583940	354	368	nephrotoxicity	Disease	D007674
11583940	376	390	nephrotoxicity	Disease	D007674
11583940	496	510	nephrotoxicity	Disease	D007674
11583940	566	580	nephrotoxicity	Disease	D007674
11583940	716	737	mycophenolate mofetil	Chemical	C063008
11583940	742	751	sirolimus	Chemical	D020123
11583940	753	762	rapamycin	Chemical	D020123
11583940	773	787	nephrotoxicity	Disease	D007674
11583940	CID	D016559	D007674
11583940	CID	D016572	D007674

11245434|t|Erythropoietin restores the anemia-induced reduction in cyclophosphamide cytotoxicity in rat tumors.
11245434|a|The aim of this study was to examine the impact of anemia prevention by recombinant human erythropoietin (rHuEPO) treatment on the cytotoxicity of cyclophosphamide in solid experimental tumors. Anemia was induced using a single dose of carboplatin (50 mg/kg i.v.) resulting in a long-lasting reduction (30%) of the hemoglobin concentration. In a second group, the development of anemia was prevented by rHuEPO (1000 IU/kg) administered s.c. three times/week starting 7 days before carboplatin application. Four days after carboplatin treatment, tumors (DS-sarcoma of the rat) were implanted s.c. onto the hind food dorsum. Neither carboplatin nor rHuEPO treatment influenced tumor growth rate per se. When tumors were treated with a single dose of cyclophosphamide (60 mg/kg i.p.) 5 days after implantation, a growth delay with a subsequent regrowth of the tumors was observed. In the anemia group, the growth delay was significantly shorter compared with nonanemic controls (13.3 days versus 8.6 days). In the group where anemia was prevented by rHuEPO treatment, growth delay was comparable with that of nonanemic controls (13.3 days). These results suggest that chemotherapy-induced anemia reduces cytotoxicity of cyclophosphamide in tumors, whereas correction of anemia by rHuEPO treatment (epoetin alpha) increases the sensitivity, probably as a result of an improved oxygen supply to tumor tissue.
11245434	28	34	anemia	Disease	D000740
11245434	56	72	cyclophosphamide	Chemical	D003520
11245434	73	85	cytotoxicity	Disease	D064420
11245434	93	99	tumors	Disease	D009369
11245434	152	158	anemia	Disease	D000740
11245434	232	244	cytotoxicity	Disease	D064420
11245434	248	264	cyclophosphamide	Chemical	D003520
11245434	287	293	tumors	Disease	D009369
11245434	295	301	Anemia	Disease	D000740
11245434	337	348	carboplatin	Chemical	D016190
11245434	480	486	anemia	Disease	D000740
11245434	582	593	carboplatin	Chemical	D016190
11245434	623	634	carboplatin	Chemical	D016190
11245434	646	652	tumors	Disease	D009369
11245434	657	664	sarcoma	Disease	D012509
11245434	732	743	carboplatin	Chemical	D016190
11245434	776	781	tumor	Disease	D009369
11245434	807	813	tumors	Disease	D009369
11245434	849	865	cyclophosphamide	Chemical	D003520
11245434	958	964	tumors	Disease	D009369
11245434	986	992	anemia	Disease	D000740
11245434	1124	1130	anemia	Disease	D000740
11245434	1287	1293	anemia	Disease	D000740
11245434	1302	1314	cytotoxicity	Disease	D064420
11245434	1318	1334	cyclophosphamide	Chemical	D003520
11245434	1338	1344	tumors	Disease	D009369
11245434	1368	1374	anemia	Disease	D000740
11245434	1474	1480	oxygen	Chemical	D010100
11245434	1491	1496	tumor	Disease	D009369
11245434	CID	D016190	D000740

11243580|t|The role of nitrergic system in lidocaine-induced convulsion in the mouse.
11243580|a|The effects of N-nitro-L-arginine-methyl ester (L-NAME) a nitric oxide (NO) synthase inhibitor and L-arginine, a NO precursor, were investigated on lidocaine-induced convulsions. In the first experiment, four groups of mice received physiological saline (0.9%), L-arginine (300 mg/kg, i.p.), L-NAME (100 mg/kg, i.p.) and diazepam (2 mg/kg), respectively. Thirty minutes after these injections, all mice received lidocaine (50 mg/kg, i.p.). In the second experiment, four groups of mice received similar treatment in the first experiment, and 30 min after these injections, all mice received a higher dose of lidocaine (80 mg/kg). L-NAME (100 mg/kg, i.p.) and diazepam (2 mg/kg) significantly decreased the incidence of lidocaine (50 mg/kg)-induced convulsions. In contrast, the L-arginine treatment increased the incidence of lidocaine (80 mg/kg, i.p.)-induced convulsions significantly. These results may suggest that NO is a proconvulsant mediator in lidocaine-induced convulsions.
11243580	32	41	lidocaine	Chemical	D008012
11243580	50	60	convulsion	Disease	D012640
11243580	90	121	N-nitro-L-arginine-methyl ester	Chemical	D019331
11243580	123	129	L-NAME	Chemical	D019331
11243580	133	145	nitric oxide	Chemical	D009569
11243580	147	149	NO	Chemical	D009569
11243580	174	184	L-arginine	Chemical	D001120
11243580	188	190	NO	Chemical	D009569
11243580	223	232	lidocaine	Chemical	D008012
11243580	241	252	convulsions	Disease	D012640
11243580	337	347	L-arginine	Chemical	D001120
11243580	367	373	L-NAME	Chemical	D019331
11243580	396	404	diazepam	Chemical	D003975
11243580	487	496	lidocaine	Chemical	D008012
11243580	683	692	lidocaine	Chemical	D008012
11243580	705	711	L-NAME	Chemical	D019331
11243580	734	742	diazepam	Chemical	D003975
11243580	794	803	lidocaine	Chemical	D008012
11243580	823	834	convulsions	Disease	D012640
11243580	853	863	L-arginine	Chemical	D001120
11243580	901	910	lidocaine	Chemical	D008012
11243580	936	947	convulsions	Disease	D012640
11243580	994	996	NO	Chemical	D009569
11243580	1028	1037	lidocaine	Chemical	D008012
11243580	1046	1057	convulsions	Disease	D012640
11243580	CID	D008012	D012640

11079278|t|Effect of intravenous metoprolol or intravenous metoprolol plus glucagon on dobutamine-induced myocardial ischemia.
11079278|a|STUDY OBJECTIVE: To determine the effect of metoprolol on dobutamine stress testing with technetium-99m sestamibi single-photon emission computed tomography imaging and ST-segment monitoring, and to assess the impact of intravenous glucagon on metoprolol's effects. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Community hospital. PATIENTS: Twenty-two patients with known reversible perfusion defects. INTERVENTION: Patients underwent dobutamine stress tests per standard protocol. Before dobutamine was begun, no therapy was given during the first visit, and patients were randomized on subsequent visits to receive metoprolol or metoprolol plus glucagon 1 mg. Metoprolol was dosed to achieve a resting predobutamine heart rate below 65 beats/minute or a total intravenous dose of 20 mg. MEASUREMENTS AND MAIN RESULTS: Metoprolol reduced maximum heart rate 31%, summed stress scores 29%, and summed difference scores 43% versus control. Metoprolol plus glucagon also reduced the maximum heart rate 29% versus control. Summed stress and summed difference scores were not significantly reduced, although they were 18% and 30% lower, respectively, than control. No significant differences were found in any parameter between metoprolol and metoprolol-glucagon. CONCLUSION: During dobutamine stress testing, metoprolol attenuates or eliminates evidence of myocardial ischemia. Glucagon 1 mg, although somewhat effective, does not correct this effect to the extent that it can be administered clinically.
11079278	22	32	metoprolol	Chemical	D008790
11079278	48	58	metoprolol	Chemical	D008790
11079278	76	86	dobutamine	Chemical	D004280
11079278	95	114	myocardial ischemia	Disease	D017202
11079278	160	170	metoprolol	Chemical	D008790
11079278	174	184	dobutamine	Chemical	D004280
11079278	205	229	technetium-99m sestamibi	Chemical	D017256
11079278	360	370	metoprolol	Chemical	D008790
11079278	575	585	dobutamine	Chemical	D004280
11079278	629	639	dobutamine	Chemical	D004280
11079278	757	767	metoprolol	Chemical	D008790
11079278	771	781	metoprolol	Chemical	D008790
11079278	802	812	Metoprolol	Chemical	D008790
11079278	844	857	predobutamine	Chemical	-1
11079278	960	970	Metoprolol	Chemical	D008790
11079278	1078	1088	Metoprolol	Chemical	D008790
11079278	1363	1373	metoprolol	Chemical	D008790
11079278	1378	1388	metoprolol	Chemical	D008790
11079278	1418	1428	dobutamine	Chemical	D004280
11079278	1445	1455	metoprolol	Chemical	D008790
11079278	1493	1512	myocardial ischemia	Disease	D017202
11079278	CID	D004280	D017202

10910842|t|Prednisolone-induced muscle dysfunction is caused more by atrophy than by altered acetylcholine receptor expression.
10910842|a|Large doses of glucocorticoids can alter muscle physiology and susceptibility to neuromuscular blocking drugs by mechanisms not clearly understood. We investigated the effects of moderate and large doses of prednisolone on muscle function and pharmacology, and their relationship to changes in muscle size and acetylcholine receptor (AChR) expression. With institutional approval, 35 Sprague-Dawley rats were randomly allocated to receive daily subcutaneous doses of 10 mg/kg prednisolone (P10 group), 100 mg/kg prednisolone (P100 group), or an equal volume of saline (S group) for 7 days. A fourth group of rats was pair fed (food restricted) with the P100 rats for 7 days (FR group). On Day 8, the nerve-evoked peak twitch tensions, tetanic tensions, and fatigability, and the dose-response curves of d-tubocurarine in the tibialis cranialis muscle were measured in vivo and related to muscle mass or expression of AChRs. Rate of body weight gain was depressed in the P100, FR, and P10 groups compared with the S group. Tibialis muscle mass was smaller in the P100 group than in the P10 or S groups. The evoked peak twitch and tetanic tensions were less in the P100 group than in the P10 or S groups, however, tension per milligram of muscle mass was greater in the P100 group than in the S group. The 50% effective dose of d-tubocurarine (microg/kg) in the tibialis muscle was smaller in the P10 (33.6 +/- 5.4) than in the S (61.9 +/- 5.0) or the P100 (71.3 +/- 9.6) groups. AChR expression was less in the P10 group than in the S group. The evoked tensions correlated with muscle mass (r(2) = 0.32, P < 0.001), however, not with expression of AChR. The 50% effective dose of d-tubocurarine did not correlate with muscle mass or AChR expression. Our results suggest that the neuromuscular dysfunction after prednisolone is dose-dependent, and derives primarily from muscle atrophy and derives less so from changes in AChR expression. IMPLICATIONS: The mechanisms by which chronic glucocorticoid therapy alters neuromuscular physiology and pharmacology are unclear. We suggest that the observed effects are dose-dependent and derive primarily from muscle atrophy and derive less from changes in acetylcholine receptor expression.
10910842	0	12	Prednisolone	Chemical	D011239
10910842	21	39	muscle dysfunction	Disease	D018908
10910842	58	65	atrophy	Disease	D001284
10910842	82	95	acetylcholine	Chemical	D000109
10910842	324	336	prednisolone	Chemical	D011239
10910842	427	440	acetylcholine	Chemical	D000109
10910842	593	605	prednisolone	Chemical	D011239
10910842	629	641	prednisolone	Chemical	D011239
10910842	852	859	tetanic	Disease	D013746
10910842	920	934	d-tubocurarine	Chemical	D014403
10910842	1246	1253	tetanic	Disease	D013746
10910842	1443	1457	d-tubocurarine	Chemical	D014403
10910842	1796	1810	d-tubocurarine	Chemical	D014403
10910842	1895	1920	neuromuscular dysfunction	Disease	D009468
10910842	1927	1939	prednisolone	Chemical	D011239
10910842	1986	2000	muscle atrophy	Disease	D009133
10910842	2267	2281	muscle atrophy	Disease	D009133
10910842	2314	2327	acetylcholine	Chemical	D000109
10910842	CID	D011239	D018908
10910842	CID	D011239	D009133

10533019|t|Rapid reversal of life-threatening diltiazem-induced tetany with calcium chloride.
10533019|a|We describe a patient who developed tetany with sudden respiratory arrest after the infusion of intravenous diltiazem. The administration of calcium chloride rapidly resolved the patient's tetany with prompt recovery of respiratory function, averting the need for more aggressive airway management and ventilatory support. The emergency physician should be aware that life-threatening tetany may accompany the administration of intravenous diltiazem and that calcium chloride may be a rapid and effective remedy.
10533019	35	44	diltiazem	Chemical	D004110
10533019	53	59	tetany	Disease	D013746
10533019	65	81	calcium chloride	Chemical	D002122
10533019	119	125	tetany	Disease	D013746
10533019	138	156	respiratory arrest	Disease	D012131
10533019	191	200	diltiazem	Chemical	D004110
10533019	224	240	calcium chloride	Chemical	D002122
10533019	272	278	tetany	Disease	D013746
10533019	468	474	tetany	Disease	D013746
10533019	523	532	diltiazem	Chemical	D004110
10533019	542	558	calcium chloride	Chemical	D002122
10533019	CID	D004110	D013746

10414674|t|Effects of nonsteroidal anti-inflammatory drugs on hemostasis in patients with aneurysmal subarachnoid hemorrhage.
10414674|a|Platelet function is impaired by nonsteroidal anti-inflammatory drugs (NSAIDs) with prominent anti-inflammatory properties. Their safety in patients undergoing intracranial surgery is under debate. Patients with aneurysmal subarachnoid hemorrhage (SAH) were randomized to receive either ketoprofen, 100 mg, three times a day (ketoprofen group, n = 9) or a weak NSAID, acetaminophen, 1 g, three times a day (acetaminophen group, n = 9) starting immediately after the diagnosis of aneurysmal SAH. Treatment was continued for 3 days postoperatively. Test blood samples were taken before treatment and surgery as well as on the first, third, and fifth postoperative mornings. Maximal platelet aggregation induced by 6 microM of adenosine diphosphate decreased after administration of ketoprofen. Aggregation was lower (P < .05) in the ketoprofen group than in the acetaminophen group just before surgery and on the third postoperative day. In contrast, maximal platelet aggregation increased in the acetaminophen group on the third postoperative day as compared with the pretreatment platelet aggregation results (P < .05). One patient in the ketoprofen group developed a postoperative intracranial hematoma. Coagulation (prothrombin time [PT], activated partial thromboplastin time [APPT], fibrinogen concentration, and antithrombin III [AT III]) was comparable between the two groups. Ketoprofen but not acetaminophen impaired platelet function in patients with SAH. If ketoprofen is used before surgery on cerebral artery aneurysms, it may pose an additional risk factor for hemorrhage.
10414674	79	113	aneurysmal subarachnoid hemorrhage	Disease	D013345
10414674	327	361	aneurysmal subarachnoid hemorrhage	Disease	D013345
10414674	363	366	SAH	Disease	D013345
10414674	402	412	ketoprofen	Chemical	D007660
10414674	441	451	ketoprofen	Chemical	D007660
10414674	483	496	acetaminophen	Chemical	D000082
10414674	522	535	acetaminophen	Chemical	D000082
10414674	594	604	aneurysmal	Disease	D017542
10414674	605	608	SAH	Disease	D013345
10414674	795	815	platelet aggregation	Disease	D001791
10414674	839	860	adenosine diphosphate	Chemical	D000244
10414674	895	905	ketoprofen	Chemical	D007660
10414674	946	956	ketoprofen	Chemical	D007660
10414674	975	988	acetaminophen	Chemical	D000082
10414674	1072	1092	platelet aggregation	Disease	D001791
10414674	1110	1123	acetaminophen	Chemical	D000082
10414674	1195	1215	platelet aggregation	Disease	D001791
10414674	1254	1264	ketoprofen	Chemical	D007660
10414674	1310	1318	hematoma	Disease	D006406
10414674	1498	1508	Ketoprofen	Chemical	D007660
10414674	1517	1530	acetaminophen	Chemical	D000082
10414674	1575	1578	SAH	Disease	D013345
10414674	1583	1593	ketoprofen	Chemical	D007660
10414674	1629	1645	artery aneurysms	Disease	D002532
10414674	1689	1699	hemorrhage	Disease	D006470
10414674	CID	D007660	D006406
10414674	CID	D007660	D001791

9523850|t|Value of methylprednisolone in prevention of the arthralgia-myalgia syndrome associated with the total dose infusion of iron dextran: a double blind randomized trial.
9523850|a|The safety and efficacy of total dose infusion (TDI) of iron dextran has been well documented. In 40% of treated patients, an arthralgia-myalgia syndrome develops. The purpose of this randomized, double-blind, prospective study was to investigate whether intravenous (i.v.) administration of methylprednisolone (MP) prevents this complication. Sixty-five patients, 34 women and 31 men, ages 36 to 80 years, received either normal saline before and after TDI (group 1), 125 mg i.v. MP before and saline after TDI (group 2), or 125 mg i.v. MP before and after TDI (group 3). Patients were observed for 72 hours and reactions were recorded and graded according to severity. Fifty-eight percent of group 1 patients, 33% of group 2, and 26% of group 3 had reactions to TDI. The severity of reactions (minimal, mild, and moderate, respectively) was as follows: group 1--6, 6, and 2; group 2--1, 5, and 0; group 3--5, 1, and 0. Data were analyzed by the two-sided Fisher's exact test using 95% confidence intervals with the approximation of Woolf. These data demonstrate that administration of MP before and after TDI reduces the frequency and severity of the arthralgia-myalgia syndrome. We conclude that 125 mg i.v. MP should be given routinely before and after TDI of iron dextran.
9523850	9	27	methylprednisolone	Chemical	D008775
9523850	49	59	arthralgia	Disease	D018771
9523850	60	67	myalgia	Disease	D063806
9523850	120	132	iron dextran	Chemical	D007505
9523850	223	235	iron dextran	Chemical	D007505
9523850	293	303	arthralgia	Disease	D018771
9523850	304	311	myalgia	Disease	D063806
9523850	459	477	methylprednisolone	Chemical	D008775
9523850	479	481	MP	Chemical	D008775
9523850	648	650	MP	Chemical	D008775
9523850	705	707	MP	Chemical	D008775
9523850	1254	1256	MP	Chemical	D008775
9523850	1320	1330	arthralgia	Disease	D018771
9523850	1331	1338	myalgia	Disease	D063806
9523850	1378	1380	MP	Chemical	D008775
9523850	1431	1443	iron dextran	Chemical	D007505
9523850	CID	D007505	D018771

8384253|t|Long-term effects of vincristine on the peripheral nervous system.
8384253|a|Forty patients with Non-Hodgkin's Lymphoma treated with vincristine between 1984 and 1990 (cumulative dose 12 mg in 18-24 weeks) were investigated in order to evaluate the long term effects of vincristine on the peripheral nervous system. The patients were interviewed with emphasis on neuropathic symptoms. Physical and quantitative sensory examination with determination of vibratory perception and thermal discrimination thresholds were performed, four to 77 months (median 34 months) after vincristine treatment. Twenty-seven patients reported neuropathic symptoms. In 13 of these 27 patients symptoms were still present at the time of examination. In these patients sensory signs and symptoms predominated. In the other 14 patients symptoms had been present in the past. Symptoms persisted maximally 40 months since cessation of therapy. There was no age difference between patients with and without complaints at the time of examination. Normal reflexes were found in two third of patients. Neuropathic complaints were not very troublesome on the long term. It is concluded that with the above mentioned vincristine dose schedule signs and symptoms of vincristine neuropathy are reversible for a great deal and prognosis is fairly good.
8384253	21	32	vincristine	Chemical	D014750
8384253	87	109	Non-Hodgkin's Lymphoma	Disease	D008228
8384253	123	134	vincristine	Chemical	D014750
8384253	260	271	vincristine	Chemical	D014750
8384253	353	373	neuropathic symptoms	Disease	D012678
8384253	561	572	vincristine	Chemical	D014750
8384253	615	635	neuropathic symptoms	Disease	D012678
8384253	1177	1188	vincristine	Chemical	D014750
8384253	1225	1236	vincristine	Chemical	D014750
8384253	1237	1247	neuropathy	Disease	D009422
8384253	CID	D014750	D012678

8268147|t|A case of polymyositis in a patient with primary biliary cirrhosis treated with D-penicillamine.
8268147|a|Although D-penicillamine has been used for many rheumatologic diseases, toxicity limits its usefulness in many patients. Polymyositis/dermatomyositis can develop as one of the autoimmune complications of D-penicillamine treatment, but its exact pathogenesis remains unclear. We report a patient with primary biliary cirrhosis, who developed polymyositis while receiving D-penicillamine therapy. We described the special clinical course of the patient. Patients receiving D-penicillamine therapy should be followed carefully for the development of autoimmune complications like polymyositis/dermatomyositis.
8268147	10	22	polymyositis	Disease	D017285
8268147	41	66	primary biliary cirrhosis	Disease	D008105
8268147	80	95	D-penicillamine	Chemical	D010396
8268147	106	121	D-penicillamine	Chemical	D010396
8268147	145	167	rheumatologic diseases	Disease	D012216
8268147	169	177	toxicity	Disease	D064420
8268147	218	230	Polymyositis	Disease	D017285
8268147	231	246	dermatomyositis	Disease	D003882
8268147	301	316	D-penicillamine	Chemical	D010396
8268147	397	422	primary biliary cirrhosis	Disease	D008105
8268147	438	450	polymyositis	Disease	D017285
8268147	467	482	D-penicillamine	Chemical	D010396
8268147	568	583	D-penicillamine	Chemical	D010396
8268147	674	686	polymyositis	Disease	D017285
8268147	687	702	dermatomyositis	Disease	D003882
8268147	CID	D010396	D017285

8251368|t|Photodistributed nifedipine-induced facial telangiectasia.
8251368|a|Five months after starting nifedipine (Adalat), two patients developed photodistributed facial telangiectasia, which became more noticeable with time. Neither patient complained of photosensitivity or flushing. Both patients reported a significant cosmetic improvement after discontinuing the drug. One commenced the closely related drug amlodipine 3 years later, with recurrence of telangiectasia. The photodistribution of the telangiectasia suggests a significant drug/light interaction.
8251368	17	27	nifedipine	Chemical	D009543
8251368	43	57	telangiectasia	Disease	D013684
8251368	86	96	nifedipine	Chemical	D009543
8251368	98	104	Adalat	Chemical	D009543
8251368	154	168	telangiectasia	Disease	D013684
8251368	260	268	flushing	Disease	D005483
8251368	397	407	amlodipine	Chemical	D017311
8251368	442	456	telangiectasia	Disease	D013684
8251368	487	501	telangiectasia	Disease	D013684
8251368	CID	D009543	D013684
8251368	CID	D017311	D013684

7542793|t|Nephrotoxicity of cyclosporin A and FK506: inhibition of calcineurin phosphatase.
7542793|a|Cyclosporin A (CsA; 50 mg/kg) and Fujimycine (FK506; 5 mg/kg), but not the related macrolide immunosuppressant rapamycin (5 mg/kg), caused a reduction of glomerular filtration rate, degenerative changes of proximal tubular epithelium, and hypertrophy of the juxtaglomerular apparatus in male Wistar rats when given for 10 days. The molecular mechanisms of CsA and FK506 toxicity were investigated. Cyclophilin A and FK506-binding protein, the main intracytoplasmic receptors for CsA and FK506, respectively, were each detected in renal tissue extract. In the kidney, high levels of immunoreactive and enzymatically active calcineurin were found which were inhibited by the immunosuppressants CsA and FK506, but not by rapamycin. Finally, specific immunophilin-drug-calcineurin complexes formed only in the presence of CsA and FK506, but not rapamycin. These results suggest that the nephrotoxic effects of CsA and FK506 is likely mediated through binding to renal immunophilin and inhibiting calcineurin phosphatase.
7542793	0	14	Nephrotoxicity	Disease	D007674
7542793	18	31	cyclosporin A	Chemical	D016572
7542793	36	41	FK506	Chemical	D016559
7542793	82	95	Cyclosporin A	Chemical	D016572
7542793	97	100	CsA	Chemical	D016572
7542793	116	126	Fujimycine	Chemical	D016559
7542793	128	133	FK506	Chemical	D016559
7542793	165	174	macrolide	Chemical	D018942
7542793	193	202	rapamycin	Chemical	D020123
7542793	321	332	hypertrophy	Disease	D006984
7542793	438	441	CsA	Chemical	D016572
7542793	446	451	FK506	Chemical	D016559
7542793	452	460	toxicity	Disease	D064420
7542793	498	503	FK506	Chemical	D016559
7542793	561	564	CsA	Chemical	D016572
7542793	569	574	FK506	Chemical	D016559
7542793	774	777	CsA	Chemical	D016572
7542793	782	787	FK506	Chemical	D016559
7542793	800	809	rapamycin	Chemical	D020123
7542793	900	903	CsA	Chemical	D016572
7542793	908	913	FK506	Chemical	D016559
7542793	923	932	rapamycin	Chemical	D020123
7542793	965	976	nephrotoxic	Disease	D007674
7542793	988	991	CsA	Chemical	D016572
7542793	996	1001	FK506	Chemical	D016559
7542793	CID	D016572	D007674
7542793	CID	D016559	D007674

7337133|t|Massive cerebral edema associated with fulminant hepatic failure in acetaminophen overdose: possible role of cranial decompression.
7337133|a|Cerebral edema may complicate the course of fulminant hepatic failure. Response to conventional therapy has been disappointing. We present a patient with fatal acetaminophen-induced fulminant hepatic failure, with signs and symptoms of cerebral edema, unresponsive to conventional medical therapy. Cranial decompression was carried out. A justification of the need for further evaluation of cranial decompression in such patients is presented.
7337133	8	22	cerebral edema	Disease	D001929
7337133	49	64	hepatic failure	Disease	D017093
7337133	68	81	acetaminophen	Chemical	D000082
7337133	82	90	overdose	Disease	D062787
7337133	132	146	Cerebral edema	Disease	D001929
7337133	176	201	fulminant hepatic failure	Disease	D017093
7337133	292	305	acetaminophen	Chemical	D000082
7337133	314	339	fulminant hepatic failure	Disease	D017093
7337133	368	382	cerebral edema	Disease	D001929
7337133	CID	D000082	D001929
7337133	CID	D000082	D017093

4069770|t|Gentamicin nephropathy in a neonate.
4069770|a|The clinical and autopsy findings in a premature baby who died of acute renal failure after therapy with gentamicin (5 mg/kg/day) and penicillin are presented. The serum gentamicin concentration had reached toxic levels when anuria developed. Numerous periodic acid Schiff (PAS) positive, diastase resistant cytoplasmic inclusion bodies which appeared as myelin figures in cytosegresomes under the electron microscope were identified in the proximal convoluted tubules. The pathological changes induced by gentamicin in the human neonatal kidneys have not been previously reported.
4069770	0	10	Gentamicin	Chemical	D005839
4069770	11	22	nephropathy	Disease	D007674
4069770	103	122	acute renal failure	Disease	D058186
4069770	142	152	gentamicin	Chemical	D005839
4069770	171	181	penicillin	Chemical	D010406
4069770	207	217	gentamicin	Chemical	D005839
4069770	262	268	anuria	Disease	D001002
4069770	289	302	periodic acid	Chemical	D010504
4069770	543	553	gentamicin	Chemical	D005839
4069770	CID	D005839	D058186

3780814|t|Anti-carcinogenic action of phenobarbital given simultaneously with diethylnitrosamine in the rat.
3780814|a|The present work has been planned in order to elucidate the effect of phenobarbital (PB: 15 mg per rat of ingested dose) on carcinogenesis when it is administered simultaneously with diethylnitrosamine (DEN: 10 mg/kg/day). Wistar rats (180 g) were treated by DEN alone or by DEN + PB during 2, 4 and 6 weeks according to our schedule for hepatocarcinogenesis. After the end of the treatment, the number and the size of induced PAS positive preneoplastic foci was significantly reduced when PB was given simultaneously with DEN for 4 and 6 weeks. The mitotic inhibition and the production of micronuclei normally observed after partial hepatectomy in DEN treated rats were also significantly decreased in DEN + PB treated rats. When the treatment last only 2 weeks, the presence of PB did not change significantly the last parameters. In DEN + PB treated rats, the survival was prolonged and the tumor incidence decreased as compared with the results obtained by DEN alone. It is concluded that PB, which promotes carcinogenesis when administered after the DEN treatment, reduces the carcinogen effect when given simultaneously with DEN. This 'anti-carcinogen' effect acts on the initiation as well as on the promotion of the precancerous lesions. Biochemical investigations are in progress to obtain more information about this 'paradoxical' PB effect.
3780814	5	17	carcinogenic	Disease	D063646
3780814	28	41	phenobarbital	Chemical	D010634
3780814	68	86	diethylnitrosamine	Chemical	D004052
3780814	169	182	phenobarbital	Chemical	D010634
3780814	184	186	PB	Chemical	D010634
3780814	223	237	carcinogenesis	Disease	D063646
3780814	282	300	diethylnitrosamine	Chemical	D004052
3780814	302	305	DEN	Chemical	D004052
3780814	358	361	DEN	Chemical	D004052
3780814	374	377	DEN	Chemical	D004052
3780814	380	382	PB	Chemical	D010634
3780814	437	457	hepatocarcinogenesis	Disease	D063646
3780814	539	557	preneoplastic foci	Disease	D011230
3780814	589	591	PB	Chemical	D010634
3780814	622	625	DEN	Chemical	D004052
3780814	749	752	DEN	Chemical	D004052
3780814	803	806	DEN	Chemical	D004052
3780814	809	811	PB	Chemical	D010634
3780814	880	882	PB	Chemical	D010634
3780814	936	939	DEN	Chemical	D004052
3780814	942	944	PB	Chemical	D010634
3780814	994	999	tumor	Disease	D009369
3780814	1061	1064	DEN	Chemical	D004052
3780814	1093	1095	PB	Chemical	D010634
3780814	1112	1126	carcinogenesis	Disease	D063646
3780814	1155	1158	DEN	Chemical	D004052
3780814	1231	1234	DEN	Chemical	D004052
3780814	1324	1344	precancerous lesions	Disease	D011230
3780814	1441	1443	PB	Chemical	D010634
3780814	CID	D004052	D011230

3780697|t|Post-operative rigidity after fentanyl administration.
3780697|a|A case of thoraco-abdominal rigidity leading to respiratory failure is described in the post-operative period in an elderly patient who received a moderate dose of fentanyl. This was successfully reversed by naloxone. The mechanisms possibly implicated in this accident are discussed.
3780697	15	23	rigidity	Disease	D009127
3780697	30	38	fentanyl	Chemical	D005283
3780697	83	91	rigidity	Disease	D009127
3780697	103	122	respiratory failure	Disease	D012131
3780697	219	227	fentanyl	Chemical	D005283
3780697	263	271	naloxone	Chemical	D009270
3780697	CID	D005283	D009127

3686155|t|Postpartum psychosis induced by bromocriptine.
3686155|a|Two multigravida patients with no prior psychiatric history were seen with postpartum psychosis, having received bromocriptine for inhibition of lactation. Bromocriptine given in high doses has been associated with psychosis in patients receiving the drug for Parkinson's disease. These cases demonstrate that bromocriptine may cause psychosis even when given in low doses.
3686155	11	20	psychosis	Disease	D011605
3686155	32	45	bromocriptine	Chemical	D001971
3686155	87	98	psychiatric	Disease	D001523
3686155	133	142	psychosis	Disease	D011605
3686155	160	173	bromocriptine	Chemical	D001971
3686155	178	201	inhibition of lactation	Disease	D007775
3686155	203	216	Bromocriptine	Chemical	D001971
3686155	262	271	psychosis	Disease	D011605
3686155	307	326	Parkinson's disease	Disease	D010300
3686155	357	370	bromocriptine	Chemical	D001971
3686155	381	390	psychosis	Disease	D011605
3686155	CID	D001971	D011605

3137399|t|A prospective study on the dose dependency of cardiotoxicity induced by mitomycin C.
3137399|a|Since 1975 mitomycin C (MMC) has been suggested to be cardiotoxic, especially when combined with or given following doxorubicin. Data on dose dependency or incidence concerning this side effect were not known. We have initiated a prospective study to obtain some more data on these subjects. Forty-four MMC-treated patients were studied, 37 of them could be evaluated. All patients were studied by repeated physical examinations, chest X-rays, electro- and echocardiography and radionuclide left ventricular ejection fraction (EF) determinations. The results were evaluated per cumulative dose level. One of the patients developed cardiac failure after 30 mg m-2 MMC and only 150 mg m-2 doxorubicin. The cardiac failure was predicted by a drop in EF determined during a cold pressor test. None of the other patients developed clinical cardiotoxicity, nor did the studied parameters change. The literature on this subject was also reviewed. Based on the combined data from the present study and the literature, we suggest that MMC-related cardiotoxicity is dose dependent, occurring at cumulative dose levels of 30 mg m-2 or more, mainly in patients also (previously or simultaneously) treated with doxorubicin. The incidence is likely to be less than 10% even for this risk group.
3137399	46	60	cardiotoxicity	Disease	D066126
3137399	72	83	mitomycin C	Chemical	D016685
3137399	96	107	mitomycin C	Chemical	D016685
3137399	109	112	MMC	Chemical	D016685
3137399	139	150	cardiotoxic	Disease	D066126
3137399	201	212	doxorubicin	Chemical	D004317
3137399	388	391	MMC	Chemical	D016685
3137399	716	731	cardiac failure	Disease	D006333
3137399	748	751	MMC	Chemical	D016685
3137399	772	783	doxorubicin	Chemical	D004317
3137399	789	804	cardiac failure	Disease	D006333
3137399	920	934	cardiotoxicity	Disease	D066126
3137399	1111	1114	MMC	Chemical	D016685
3137399	1123	1137	cardiotoxicity	Disease	D066126
3137399	1283	1294	doxorubicin	Chemical	D004317
3137399	CID	D016685	D006333
3137399	CID	D004317	D006333

2709684|t|Phlorizin-induced glycosuria does not prevent gentamicin nephrotoxicity in rats.
2709684|a|Because rats with streptozotocin-induced diabetes mellitus (DM) have a high solute diuresis (glycosuria of 10 to 12 g/day), we have suggested that this may in part be responsible for their resistance to gentamicin-induced acute renal failure (ARF). The protection from gentamicin nephrotoxicity was studied in non-diabetic rats with chronic solute diuresis induced by blockage of tubular glucose reabsorption with phlorizin (P). DM rats with mild glycosuria (similar in degree to that of the P treated animals) were also studied. Unanesthetized adult female, Sprague-Dawley rats were divided in four groups and studied for 15 days. Group 1 (P alone) received P, 360 mg/day, for 15 days; Group II (P + gentamicin); Group III (gentamicin alone) and Group IV (mild DM + gentamicin). Nephrotoxic doses (40 mg/kg body wt/day) of gentamicin were injected during the last nine days of study to the animals of groups II to IV. In Group I, P induced a moderate and stable glycosuria (3.9 +/- 0.1 g/day, SE), and no functional or morphologic evidence of renal dysfunction (baseline CCr 2.1 +/- 0.1 ml/min, undetectable lysozymuria) or damage (tubular necrosis score [maximum 4], zero). In Group II, P did not prevent gentamicin-ARF (maximal decrease in CCr at day 9.89%, P less than 0.001; peak lysozymuria, 1863 +/- 321 micrograms/day; and tubular necrosis score, 3.9 +/- 0.1). These values were not different from those of Group III: maximal decrease in CCr 73% (P less than 0.001); lysozymuria, 2147 +/- 701 micrograms/day; tubular necrosis score, 3.8 +/- 0.1.(ABSTRACT TRUNCATED AT 250 WORDS)
2709684	0	9	Phlorizin	Chemical	D010695
2709684	18	28	glycosuria	Disease	D006029
2709684	46	56	gentamicin	Chemical	D005839
2709684	57	71	nephrotoxicity	Disease	D007674
2709684	99	113	streptozotocin	Chemical	D013311
2709684	122	139	diabetes mellitus	Disease	D003920
2709684	141	143	DM	Disease	D003920
2709684	174	184	glycosuria	Disease	D006029
2709684	284	294	gentamicin	Chemical	D005839
2709684	303	322	acute renal failure	Disease	D058186
2709684	324	327	ARF	Disease	D058186
2709684	350	360	gentamicin	Chemical	D005839
2709684	361	375	nephrotoxicity	Disease	D007674
2709684	395	403	diabetic	Disease	D003920
2709684	469	476	glucose	Chemical	D005947
2709684	495	504	phlorizin	Chemical	D010695
2709684	506	507	P	Chemical	D010695
2709684	510	512	DM	Disease	D003920
2709684	528	538	glycosuria	Disease	D006029
2709684	573	574	P	Chemical	D010695
2709684	722	723	P	Chemical	D010695
2709684	740	741	P	Chemical	D010695
2709684	778	779	P	Chemical	D010695
2709684	782	792	gentamicin	Chemical	D005839
2709684	806	816	gentamicin	Chemical	D005839
2709684	843	845	DM	Disease	D003920
2709684	848	858	gentamicin	Chemical	D005839
2709684	861	872	Nephrotoxic	Disease	D007674
2709684	905	915	gentamicin	Chemical	D005839
2709684	1012	1013	P	Chemical	D010695
2709684	1044	1054	glycosuria	Disease	D006029
2709684	1125	1142	renal dysfunction	Disease	D007674
2709684	1214	1230	tubular necrosis	Disease	D009956
2709684	1270	1271	P	Chemical	D010695
2709684	1288	1298	gentamicin	Chemical	D005839
2709684	1299	1302	ARF	Disease	D058186
2709684	1342	1343	P	Chemical	D010695
2709684	1412	1428	tubular necrosis	Disease	D009956
2709684	1536	1537	P	Chemical	D010695
2709684	1598	1614	tubular necrosis	Disease	D009956
2709684	CID	D013311	D003920
2709684	CID	D005839	D058186

458486|t|Tiapride in levodopa-induced involuntary movements.
458486|a|Tiapride, a substituted benzamide derivative closely related to metoclopramide, reduced levodopa-induced peak dose involuntary movements in 16 patients with idiopathic Parkinson's disease. However, an unacceptable increase in disability from Parkinsonism with aggravation of end-of-dose akinesia led to its cessation in 14 patients. Tiapride had no effect on levodopa-induced early morning of "off-period" segmental dystonia. These results fail to support the notion that levodopa-induced dyskinesias are caused by overstimulation of a separate group of dopamine receptors.
458486	0	8	Tiapride	Chemical	D063325
458486	12	20	levodopa	Chemical	D007980
458486	29	50	involuntary movements	Disease	D004409
458486	52	60	Tiapride	Chemical	D063325
458486	76	85	benzamide	Chemical	C037689
458486	116	130	metoclopramide	Chemical	D008787
458486	140	148	levodopa	Chemical	D007980
458486	167	188	involuntary movements	Disease	D004409
458486	209	239	idiopathic Parkinson's disease	Disease	D010300
458486	294	306	Parkinsonism	Disease	D010300
458486	339	347	akinesia	Disease	D004409
458486	385	393	Tiapride	Chemical	D063325
458486	411	419	levodopa	Chemical	D007980
458486	468	476	dystonia	Disease	D004421
458486	524	532	levodopa	Chemical	D007980
458486	541	552	dyskinesias	Disease	D004409
458486	606	614	dopamine	Chemical	D004298
458486	CID	D007980	D004409

21294084|t|Effects of the hippocampal deep brain stimulation on cortical epileptic discharges in penicillin - induced epilepsy model in rats.
21294084|a|AIM: Experimental and clinical studies have revealed that hippocampal DBS can control epileptic activity, but the mechanism of action is obscure and optimal stimulation parameters are not clearly defined. The aim was to evaluate the effects of high frequency hippocampal stimulation on cortical epileptic activity in penicillin-induced epilepsy model. MATERIAL AND METHODS: Twenty-five Sprague-Dawley rats were implanted DBS electrodes. In group-1 (n=10) hippocampal DBS was off and in the group-2 (n=10) hippocampal DBS was on (185 Hz, 0.5V, 1V, 2V, and 5V for 60 sec) following penicillin G injection intracortically. In the control group hippocampal DBS was on following 8  l saline injection intracortically. EEG recordings were obtained before and 15 minutes following penicillin-G injection, and at 10th minutes following each stimulus for analysis in terms of frequency, amplitude, and power spectrum. RESULTS: High frequency hippocampal DBS suppressed the acute penicillin-induced cortical epileptic activity independent from stimulus intensity. In the control group, hippocampal stimulation alone lead only to diffuse slowing of cerebral bioelectrical activity at 5V stimulation. CONCLUSION: Our results revealed that continuous high frequency stimulation of the hippocampus suppressed acute cortical epileptic activity effectively without causing secondary epileptic discharges. These results are important in terms of defining the optimal parameters of hippocampal DBS in patients with epilepsy.
21294084	62	71	epileptic	Disease	D004827
21294084	86	96	penicillin	Chemical	D010406
21294084	107	115	epilepsy	Disease	D004827
21294084	217	226	epileptic	Disease	D004827
21294084	426	435	epileptic	Disease	D004827
21294084	448	458	penicillin	Chemical	D010406
21294084	467	475	epilepsy	Disease	D004827
21294084	711	723	penicillin G	Chemical	D010400
21294084	905	917	penicillin-G	Chemical	D010400
21294084	1101	1111	penicillin	Chemical	D010406
21294084	1129	1138	epileptic	Disease	D004827
21294084	1441	1450	epileptic	Disease	D004827
21294084	1498	1507	epileptic	Disease	D004827
21294084	1628	1636	epilepsy	Disease	D004827
21294084	CID	D010400	D004827

20727411|t|Neural correlates of S-ketamine induced psychosis during overt continuous verbal fluency.
20727411|a|The glutamatergic N-methyl-D-aspartate (NMDA) receptor has been implicated in the pathophysiology of schizophrenia. Administered to healthy volunteers, a subanesthetic dose of the non-competitive NMDA receptor antagonist ketamine leads to psychopathological symptoms similar to those observed in schizophrenia. In patients with schizophrenia, ketamine exacerbates the core symptoms of illness, supporting the hypothesis of a glutamatergic dysfunction. In a counterbalanced, placebo-controlled, double-blind study design, healthy subjects were administered a continuous subanesthetic S-ketamine infusion while differences in BOLD responses measured with fMRI were detected. During the scanning period, subjects performed continuous overt verbal fluency tasks (phonological, lexical and semantic). Ketamine-induced psychopathological symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Ketamine elicited psychosis like psychopathology. Post-hoc t-tests revealed significant differences between placebo and ketamine for the amounts of words generated during lexical and semantic verbal fluency, while the phonological domain remained unaffected. Ketamine led to enhanced cortical activations in supramarginal and frontal brain regions for phonological and lexical verbal fluency, but not for semantic verbal fluency. Ketamine induces activation changes in healthy subjects similar to those observed in patients with schizophrenia, particularly in frontal and temporal brain regions. Our results provide further support for the hypothesis of an NMDA receptor dysfunction in the pathophysiology of schizophrenia.
20727411	21	31	S-ketamine	Chemical	-1
20727411	40	49	psychosis	Disease	D011605
20727411	108	128	N-methyl-D-aspartate	Chemical	D016202
20727411	130	134	NMDA	Chemical	D016202
20727411	191	204	schizophrenia	Disease	D012559
20727411	286	290	NMDA	Chemical	D016202
20727411	311	319	ketamine	Chemical	D007649
20727411	386	399	schizophrenia	Disease	D012559
20727411	418	431	schizophrenia	Disease	D012559
20727411	433	441	ketamine	Chemical	D007649
20727411	515	540	glutamatergic dysfunction	Disease	D018754
20727411	673	683	S-ketamine	Chemical	-1
20727411	886	894	Ketamine	Chemical	D007649
20727411	1000	1008	Ketamine	Chemical	D007649
20727411	1018	1027	psychosis	Disease	D011605
20727411	1120	1128	ketamine	Chemical	D007649
20727411	1259	1267	Ketamine	Chemical	D007649
20727411	1430	1438	Ketamine	Chemical	D007649
20727411	1529	1542	schizophrenia	Disease	D012559
20727411	1657	1661	NMDA	Chemical	D016202
20727411	1709	1722	schizophrenia	Disease	D012559
20727411	CID	D007649	D011605

20533999|t|Dopamine is not essential for the development of methamphetamine-induced neurotoxicity.
20533999|a|It is widely believed that dopamine (DA) mediates methamphetamine (METH)-induced toxicity to brain dopaminergic neurons, because drugs that interfere with DA neurotransmission decrease toxicity, whereas drugs that increase DA neurotransmission enhance toxicity. However, temperature effects of drugs that have been used to manipulate brain DA neurotransmission confound interpretation of the data. Here we show that the recently reported ability of L-dihydroxyphenylalanine to reverse the protective effect of alpha-methyl-para-tyrosine on METH-induced DA neurotoxicity is also confounded by drug effects on body temperature. Further, we show that mice genetically engineered to be deficient in brain DA develop METH neurotoxicity, as long as the thermic effects of METH are preserved. In addition, we demonstrate that mice genetically engineered to have unilateral brain DA deficits develop METH-induced dopaminergic deficits that are of comparable magnitude on both sides of the brain. Taken together, these findings demonstrate that DA is not essential for the development of METH-induced dopaminergic neurotoxicity and suggest that mechanisms independent of DA warrant more intense investigation.
20533999	0	8	Dopamine	Chemical	D004298
20533999	49	64	methamphetamine	Chemical	D008694
20533999	73	86	neurotoxicity	Disease	D020258
20533999	115	123	dopamine	Chemical	D004298
20533999	125	127	DA	Chemical	D004298
20533999	138	153	methamphetamine	Chemical	D008694
20533999	155	159	METH	Chemical	D008694
20533999	169	177	toxicity	Disease	D064420
20533999	243	245	DA	Chemical	D004298
20533999	273	281	toxicity	Disease	D064420
20533999	311	313	DA	Chemical	D004298
20533999	340	348	toxicity	Disease	D064420
20533999	428	430	DA	Chemical	D004298
20533999	537	561	L-dihydroxyphenylalanine	Chemical	D007980
20533999	598	624	alpha-methyl-para-tyrosine	Chemical	D019805
20533999	628	632	METH	Chemical	D008694
20533999	641	643	DA	Chemical	D004298
20533999	644	657	neurotoxicity	Disease	D020258
20533999	789	791	DA	Chemical	D004298
20533999	800	804	METH	Chemical	D008694
20533999	805	818	neurotoxicity	Disease	D020258
20533999	854	858	METH	Chemical	D008694
20533999	960	962	DA	Chemical	D004298
20533999	980	984	METH	Chemical	D008694
20533999	993	1014	dopaminergic deficits	Disease	D009461
20533999	1124	1126	DA	Chemical	D004298
20533999	1167	1171	METH	Chemical	D008694
20533999	1193	1206	neurotoxicity	Disease	D020258
20533999	1250	1252	DA	Chemical	D004298
20533999	CID	D008694	D020258

20304337|t|Brainstem dysgenesis in an infant prenatally exposed to cocaine.
20304337|a|Many authors described the effects on the fetus of maternal cocaine abuse during pregnancy. Vasoconstriction appears to be the common mechanism of action leading to a wide range of fetal anomalies. We report on an infant with multiple cranial-nerve involvement attributable to brainstem dysgenesis, born to a cocaine-addicted mother.
20304337	0	20	Brainstem dysgenesis	Disease	-1
20304337	56	63	cocaine	Chemical	D003042
20304337	125	138	cocaine abuse	Disease	D019970
20304337	246	261	fetal anomalies	Disease	D005315
20304337	291	325	multiple cranial-nerve involvement	Disease	D003389
20304337	342	362	brainstem dysgenesis	Disease	-1
20304337	374	390	cocaine-addicted	Disease	D019970
20304337	CID	D003042	D003389

20103708|t|The protective role of Nrf2 in streptozotocin-induced diabetic nephropathy.
20103708|a|OBJECTIVE: Diabetic nephropathy is one of the major causes of renal failure, which is accompanied by the production of reactive oxygen species (ROS). Nrf2 is the primary transcription factor that controls the antioxidant response essential for maintaining cellular redox homeostasis. Here, we report our findings demonstrating a protective role of Nrf2 against diabetic nephropathy. RESEARCH DESIGN AND METHODS: We explore the protective role of Nrf2 against diabetic nephropathy using human kidney biopsy tissues from diabetic nephropathy patients, a streptozotocin-induced diabetic nephropathy model in Nrf2(-/-) mice, and cultured human mesangial cells. RESULTS: The glomeruli of human diabetic nephropathy patients were under oxidative stress and had elevated Nrf2 levels. In the animal study, Nrf2 was demonstrated to be crucial in ameliorating streptozotocin-induced renal damage. This is evident by Nrf2(-/-) mice having higher ROS production and suffering from greater oxidative DNA damage and renal injury compared with Nrf2(+/+) mice. Mechanistic studies in both in vivo and in vitro systems showed that the Nrf2-mediated protection against diabetic nephropathy is, at least, partially through inhibition of transforming growth factor-beta1 (TGF-beta1) and reduction of extracellular matrix production. In human renal mesangial cells, high glucose induced ROS production and activated expression of Nrf2 and its downstream genes. Furthermore, activation or overexpression of Nrf2 inhibited the promoter activity of TGF-beta1 in a dose-dependent manner, whereas knockdown of Nrf2 by siRNA enhanced TGF-beta1 transcription and fibronectin production. CONCLUSIONS: This work clearly indicates a protective role of Nrf2 in diabetic nephropathy, suggesting that dietary or therapeutic activation of Nrf2 could be used as a strategy to prevent or slow down the progression of diabetic nephropathy.
20103708	31	45	streptozotocin	Chemical	D013311
20103708	54	74	diabetic nephropathy	Disease	D003928
20103708	87	107	Diabetic nephropathy	Disease	D003928
20103708	138	151	renal failure	Disease	D051437
20103708	204	210	oxygen	Chemical	D010100
20103708	437	457	diabetic nephropathy	Disease	D003928
20103708	535	555	diabetic nephropathy	Disease	D003928
20103708	595	615	diabetic nephropathy	Disease	D003928
20103708	628	642	streptozotocin	Chemical	D013311
20103708	651	671	diabetic nephropathy	Disease	D003928
20103708	765	785	diabetic nephropathy	Disease	D003928
20103708	926	940	streptozotocin	Chemical	D013311
20103708	949	961	renal damage	Disease	D058186
20103708	1078	1090	renal injury	Disease	D058186
20103708	1227	1247	diabetic nephropathy	Disease	D003928
20103708	1426	1433	glucose	Chemical	D005947
20103708	1805	1825	diabetic nephropathy	Disease	D003928
20103708	1956	1976	diabetic nephropathy	Disease	D003928
20103708	CID	D013311	D003928

19996135|t|High-dose tranexamic Acid is associated with nonischemic clinical seizures in cardiac surgical patients.
19996135|a|BACKGROUND: In 2 separate centers, we observed a notable increase in the incidence of postoperative convulsive seizures from 1.3% to 3.8% in patients having undergone major cardiac surgical procedures. These events were temporally coincident with the initial use of high-dose tranexamic acid (TXA) therapy after withdrawal of aprotinin from general clinical usage. The purpose of this review was to perform a retrospective analysis to examine whether there was a relation between TXA usage and seizures after cardiac surgery. METHODS: An in-depth chart review was undertaken in all 24 patients who developed perioperative seizures. Electroencephalographic activity was recorded in 11 of these patients, and all patients had a formal neurological evaluation and brain imaging studies. RESULTS: Twenty-one of the 24 patients did not have evidence of new cerebral ischemic injury, but seizures were likely due to ischemic brain injury in 3 patients. All patients with seizures did not have permanent neurological abnormalities. All 24 patients with seizures received high doses of TXA intraoperatively ranging from 61 to 259 mg/kg, had a mean age of 69.9 years, and 21 of 24 had undergone open chamber rather than coronary bypass procedures. All but one patient were managed using cardiopulmonary bypass. No evidence of brain ischemic, metabolic, or hyperthermia-induced causes for their seizures was apparent. CONCLUSION: Our results suggest that use of high-dose TXA in older patients in conjunction with cardiopulmonary bypass and open-chamber cardiac surgery is associated with clinical seizures in susceptible patients.
19996135	10	25	tranexamic Acid	Chemical	D014148
19996135	66	74	seizures	Disease	D012640
19996135	205	215	convulsive	Disease	D012640
19996135	216	224	seizures	Disease	D012640
19996135	381	396	tranexamic acid	Chemical	D014148
19996135	398	401	TXA	Chemical	D014148
19996135	585	588	TXA	Chemical	D014148
19996135	599	607	seizures	Disease	D012640
19996135	727	735	seizures	Disease	D012640
19996135	957	981	cerebral ischemic injury	Disease	D001930
19996135	987	995	seizures	Disease	D012640
19996135	1015	1036	ischemic brain injury	Disease	D001930
19996135	1070	1078	seizures	Disease	D012640
19996135	1102	1128	neurological abnormalities	Disease	D009422
19996135	1151	1159	seizures	Disease	D012640
19996135	1183	1186	TXA	Chemical	D014148
19996135	1422	1436	brain ischemic	Disease	D002546
19996135	1452	1464	hyperthermia	Disease	D005334
19996135	1490	1498	seizures	Disease	D012640
19996135	1567	1570	TXA	Chemical	D014148
19996135	1693	1701	seizures	Disease	D012640
19996135	CID	D014148	D012640

19674115|t|Recurrent dysosmia induced by pyrazinamide.
19674115|a|Pyrazinamide can have adverse effects such as hepatic toxicity, hyperuricemia or digestive disorders. In rare cases, alterations in taste and smell function have been reported for pyrazinamide when combined with other drugs. We report a case of reversible olfactory disorder related to pyrazinamide in a woman, with a positive rechallenge. The patient presented every day a sensation of smelling something burning 15 min after drug intake. Dysosmia disappeared completely after pyrazinamide withdrawal and recurred after its rechallenge. The case was reported to the Tunisian Centre of Pharmacovigilance.
19674115	10	18	dysosmia	Disease	D000857
19674115	30	42	pyrazinamide	Chemical	D011718
19674115	44	56	Pyrazinamide	Chemical	D011718
19674115	90	106	hepatic toxicity	Disease	D056486
19674115	108	121	hyperuricemia	Disease	D033461
19674115	224	236	pyrazinamide	Chemical	D011718
19674115	300	318	olfactory disorder	Disease	D000857
19674115	330	342	pyrazinamide	Chemical	D011718
19674115	484	492	Dysosmia	Disease	D000857
19674115	522	534	pyrazinamide	Chemical	D011718
19674115	CID	D011718	D000857

19139001|t|Longitudinal assessment of air conduction audiograms in a phase III clinical trial of difluoromethylornithine and sulindac for prevention of sporadic colorectal adenomas.
19139001|a|A phase III clinical trial assessed the recurrence of adenomatous polyps after treatment for 36 months with difluoromethylornithine (DFMO) plus sulindac or matched placebos. Temporary hearing loss is a known toxicity of treatment with DFMO, thus a comprehensive approach was developed to analyze serial air conduction audiograms. The generalized estimating equation method estimated the mean difference between treatment arms with regard to change in air conduction pure tone thresholds while accounting for within-subject correlation due to repeated measurements at frequencies. Based on 290 subjects, there was an average difference of 0.50 dB between subjects treated with DFMO plus sulindac compared with those treated with placebo (95% confidence interval, -0.64 to 1.63 dB; P = 0.39), adjusted for baseline values, age, and frequencies. In the normal speech range of 500 to 3,000 Hz, an estimated difference of 0.99 dB (-0.17 to 2.14 dB; P = 0.09) was detected. Dose intensity did not add information to models. There were 14 of 151 (9.3%) in the DFMO plus sulindac group and 4 of 139 (2.9%) in the placebo group who experienced at least 15 dB hearing reduction from baseline in 2 or more consecutive frequencies across the entire range tested (P = 0.02). Follow-up air conduction done at least 6 months after end of treatment showed an adjusted mean difference in hearing thresholds of 1.08 dB (-0.81 to 2.96 dB; P = 0.26) between treatment arms. There was no significant difference in the proportion of subjects in the DFMO plus sulindac group who experienced clinically significant hearing loss compared with the placebo group. The estimated attributable risk of ototoxicity from exposure to the drug is 8.4% (95% confidence interval, -2.0% to 18.8%; P = 0.12). There is a <2 dB difference in mean threshold for patients treated with DFMO plus sulindac compared with those treated with placebo.
19139001	86	109	difluoromethylornithine	Chemical	D000518
19139001	114	122	sulindac	Chemical	D013467
19139001	150	169	colorectal adenomas	Disease	D015179
19139001	225	243	adenomatous polyps	Disease	D018256
19139001	279	302	difluoromethylornithine	Chemical	D000518
19139001	304	308	DFMO	Chemical	D000518
19139001	315	323	sulindac	Chemical	D013467
19139001	355	367	hearing loss	Disease	D034381
19139001	379	387	toxicity	Disease	D064420
19139001	406	410	DFMO	Chemical	D000518
19139001	847	851	DFMO	Chemical	D000518
19139001	857	865	sulindac	Chemical	D013467
19139001	1224	1228	DFMO	Chemical	D000518
19139001	1234	1242	sulindac	Chemical	D013467
19139001	1698	1702	DFMO	Chemical	D000518
19139001	1708	1716	sulindac	Chemical	D013467
19139001	1762	1774	hearing loss	Disease	D034381
19139001	1843	1854	ototoxicity	Disease	D006311
19139001	2014	2018	DFMO	Chemical	D000518
19139001	2024	2032	sulindac	Chemical	D013467
19139001	CID	D013467	D034381

18239197|t|Increased mental slowing associated with the APOE epsilon4 allele after trihexyphenidyl oral anticholinergic challenge in healthy elderly.
18239197|a|OBJECTIVES: The objectives of this study were to examine the relationship between APOE epsilon4 and subjective effects of trihexyphenidyl on measures reflecting sedation and confusion and to investigate the relationship between trihexyphenidyl-induced subjective effects and objective memory performance. METHODS: This study comprised 24 cognitively intact, health elderly adults (12 APOE epsilon4 carriers) at an outpatient geriatric psychiatry research clinic. This was a randomized, double blind, placebo-controlled, three-way, crossover experimental design. All participants received 1.0 mg or 2.0 mg trihexyphenidyl or placebo administered in counterbalanced sequences over a period of three consecutive weeks. Bond and Lader's visual analog scales and alternate versions of the Buschke Selective Reminding Test were administered in a repeated measures design at baseline, 1, 2.5, and 5 hours postdrug administration. RESULTS: A 2.0-mg oral dose of trihexyphenidyl resulted in increased subjective ratings of mental slowness in carriers of the APOE epsilon4 allele only. Drug effects as determined by difference scores between 2.0 mg trihexyphenidyl and placebo on ratings of mental slowness significantly correlated with total and delayed recall on the Buschke Selective Reminding Test in carriers of the APOE epsilon4 allele only. However, no significant effects were found with other visual analog scales reflecting subjective sedation and clear-headedness. CONCLUSION: The epsilon4 allele in healthy elderly was associated with increased subjective mental slowing after trihexyphenidyl anticholinergic challenge.
18239197	10	24	mental slowing	Disease	D003072
18239197	72	87	trihexyphenidyl	Chemical	D014282
18239197	261	276	trihexyphenidyl	Chemical	D014282
18239197	313	322	confusion	Disease	D003221
18239197	367	382	trihexyphenidyl	Chemical	D014282
18239197	744	759	trihexyphenidyl	Chemical	D014282
18239197	1093	1108	trihexyphenidyl	Chemical	D014282
18239197	1153	1168	mental slowness	Disease	D003072
18239197	1278	1293	trihexyphenidyl	Chemical	D014282
18239197	1320	1335	mental slowness	Disease	D003072
18239197	1697	1711	mental slowing	Disease	D003072
18239197	1718	1733	trihexyphenidyl	Chemical	D014282
18239197	CID	D014282	D003072

17194457|t|Behavioral effects of pubertal anabolic androgenic steroid exposure in male rats with low serotonin.
17194457|a|The goal of this study was to assess the interactive effects of chronic anabolic androgenic steroid (AAS) exposure and brain serotonin (5-hydroxytryptamine, 5-HT) depletion on behavior of pubertal male rats. Serotonin was depleted beginning on postnatal day 26 with parachlorophenylalanine (PCPA 100 mg/kg, every other day); controls received saline. At puberty (P40), half the PCPA-treated rats and half the saline-treated rats began treatment with testosterone (T, 5 mg/kg, 5 days/week). Behavioral measures included locomotion, irritability, copulation, partner preference, and aggression. Animals were tested for aggression in their home cage, both with and without physical provocation (mild tail pinch). Brain levels of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were determined using HPLC. PCPA significantly and substantially depleted 5-HT and 5-HIAA in all brain regions examined. Chronic T treatment significantly decreased 5-HT and 5-HIAA in certain brain areas, but to a much lesser extent than PCPA. Chronic exposure to PCPA alone significantly decreased locomotor activity and increased irritability but had no effect on sexual behavior, partner preference, or aggression. T alone had no effect on locomotion, irritability, or sexual behavior but increased partner preference and aggression. The most striking effect of combining T+PCPA was a significant increase in attack frequency as well as a significant decrease in the latency to attack, particularly following physical provocation. Based on these data, it can be speculated that pubertal AAS users with low central 5-HT may be especially prone to exhibit aggressive behavior.
17194457	51	58	steroid	Chemical	D013256
17194457	90	99	serotonin	Chemical	D012701
17194457	193	200	steroid	Chemical	D013256
17194457	226	235	serotonin	Chemical	D012701
17194457	237	256	5-hydroxytryptamine	Chemical	D012701
17194457	258	262	5-HT	Chemical	D012701
17194457	309	318	Serotonin	Chemical	D012701
17194457	367	390	parachlorophenylalanine	Chemical	-1
17194457	392	396	PCPA	Chemical	-1
17194457	479	483	PCPA	Chemical	-1
17194457	551	563	testosterone	Chemical	D013739
17194457	565	566	T	Chemical	D013739
17194457	632	644	irritability	Disease	D001523
17194457	682	692	aggression	Disease	D001523
17194457	718	728	aggression	Disease	D001523
17194457	827	831	5-HT	Chemical	D012701
17194457	852	878	5-hydroxyindoleacetic acid	Chemical	D006897
17194457	880	886	5-HIAA	Chemical	D006897
17194457	917	921	PCPA	Chemical	-1
17194457	963	967	5-HT	Chemical	D012701
17194457	972	978	5-HIAA	Chemical	D006897
17194457	1018	1019	T	Chemical	D013739
17194457	1054	1058	5-HT	Chemical	D012701
17194457	1063	1069	5-HIAA	Chemical	D006897
17194457	1127	1131	PCPA	Chemical	-1
17194457	1153	1157	PCPA	Chemical	-1
17194457	1221	1233	irritability	Disease	D001523
17194457	1295	1305	aggression	Disease	D001523
17194457	1307	1308	T	Chemical	D013739
17194457	1344	1356	irritability	Disease	D001523
17194457	1414	1424	aggression	Disease	D001523
17194457	1464	1465	T	Chemical	D013739
17194457	1466	1470	PCPA	Chemical	-1
17194457	1706	1710	5-HT	Chemical	D012701
17194457	1746	1765	aggressive behavior	Disease	D001523
17194457	CID	D013739	D001523

16132524|t|Intracavitary chemotherapy (paclitaxel/carboplatin liquid crystalline cubic phases) for recurrent glioblastoma -- clinical observations.
16132524|a|Human malignant brain tumors have a poor prognosis in spite of surgery and radiation therapy. Cubic phases consist of curved biocontinuous lipid bilayers, separating two congruent networks of water channels. Used as a host for cytotoxic drugs, the gel-like matrix can easily be applied to the walls of a surgical resection cavity. For human glioblastoma recurrences, the feasibility, safety, and short-term effects of a surgical intracavitary application of paclitaxel and carboplatin encapsulated by liquid crystalline cubic phases are examined in a pilot study. A total of 12 patients with a recurrence of a glioblastoma multiforme underwent re-resection and received an intracavitary application of paclitaxel and carboplatin cubic phases in different dosages. Six of the patients received more than 15 mg paclitaxel and suffered from moderate to severe brain edema, while the remaining patients received only a total of 15 mg paclitaxel. In the latter group, brain edema was markedly reduced and dealt medically. Intracavitary chemotherapy in recurrent glioblastoma using cubic phases is feasible and safe, yet the clinical benefit remains to be examined in a clinical phase II study.
16132524	28	38	paclitaxel	Chemical	D017239
16132524	39	50	carboplatin	Chemical	D016190
16132524	98	110	glioblastoma	Disease	D005909
16132524	153	165	brain tumors	Disease	D001932
16132524	478	490	glioblastoma	Disease	D005909
16132524	595	605	paclitaxel	Chemical	D017239
16132524	610	621	carboplatin	Chemical	D016190
16132524	747	759	glioblastoma	Disease	D005909
16132524	839	849	paclitaxel	Chemical	D017239
16132524	854	865	carboplatin	Chemical	D016190
16132524	946	956	paclitaxel	Chemical	D017239
16132524	994	1005	brain edema	Disease	D001929
16132524	1067	1077	paclitaxel	Chemical	D017239
16132524	1100	1111	brain edema	Disease	D001929
16132524	1194	1206	glioblastoma	Disease	D005909
16132524	CID	D017239	D001929

12907924|t|Methylphenidate-induced obsessive-compulsive symptoms in an elderly man.
12907924|a|An 82-year-old man with treatment-resistant depression and early Alzheimer's disease was started on methylphenidate. Significant obsessive-compulsive behavior ensued but diminished over several weeks when methylphenidate was replaced by fluvoxamine. The patient had no prior psychiatric history, but he had a sister with obsessive-compulsive disorder. It appears that methylphenidate precipitated the patient's pathological behavior.
12907924	0	15	Methylphenidate	Chemical	D008774
12907924	24	53	obsessive-compulsive symptoms	Disease	D009771
12907924	97	127	treatment-resistant depression	Disease	D061218
12907924	138	157	Alzheimer's disease	Disease	D000544
12907924	173	188	methylphenidate	Chemical	D008774
12907924	202	231	obsessive-compulsive behavior	Disease	D009771
12907924	278	293	methylphenidate	Chemical	D008774
12907924	310	321	fluvoxamine	Chemical	D016666
12907924	348	359	psychiatric	Disease	D001523
12907924	394	423	obsessive-compulsive disorder	Disease	D009771
12907924	441	456	methylphenidate	Chemical	D008774
12907924	CID	D008774	D009771

12139551|t|Cardiac arrest after intravenous metoclopramide - a case of five repeated injections of metoclopramide causing five episodes of cardiac arrest.
12139551|a|We describe a patient where intravenous injection of metoclopramide was immediately followed by asystole repeatedly. The patient received metoclopramide 10 mg i.v. five times during 48 h. After interviewing the attending nurses and reviewing the written documentation, it is clear that every administration of metoclopramide was immediately (within s) followed by asystole. The asystole lasted 15-30 s on four occasions, on one occasion it lasted 2 min. The patient received atropine 0.5-1 mg and chest compressions, before sinus rhythm again took over. We interpret this as episodes of cardiac arrest caused by metoclopramide. The rapid injection via the central venous route and the concomitant tapering of dopamine infusion might have contributed in precipitating the adverse drug reaction.
12139551	0	14	Cardiac arrest	Disease	D006323
12139551	33	47	metoclopramide	Chemical	D008787
12139551	88	102	metoclopramide	Chemical	D008787
12139551	128	142	cardiac arrest	Disease	D006323
12139551	197	211	metoclopramide	Chemical	D008787
12139551	240	248	asystole	Disease	D006323
12139551	282	296	metoclopramide	Chemical	D008787
12139551	454	468	metoclopramide	Chemical	D008787
12139551	508	516	asystole	Disease	D006323
12139551	522	530	asystole	Disease	D006323
12139551	619	627	atropine	Chemical	D001285
12139551	731	745	cardiac arrest	Disease	D006323
12139551	756	770	metoclopramide	Chemical	D008787
12139551	853	861	dopamine	Chemical	D004298
12139551	CID	D008787	D006323

10411803|t|Severe immune hemolytic anemia associated with prophylactic use of cefotetan in obstetric and gynecologic procedures.
10411803|a|Second- and third-generation cephalosporins, especially cefotetan, are increasingly associated with severe, sometimes fatal immune hemolytic anemia. We noticed that 10 of our 35 cases of cefotetan-induced hemolytic anemias were in patients who had received cefotetan prophylactically for obstetric and gynecologic procedures. Eight of these cases of severe immune hemolytic anemia are described.
10411803	14	30	hemolytic anemia	Disease	D000743
10411803	67	76	cefotetan	Chemical	D015313
10411803	147	161	cephalosporins	Chemical	D002511
10411803	174	183	cefotetan	Chemical	D015313
10411803	249	265	hemolytic anemia	Disease	D000743
10411803	305	314	cefotetan	Chemical	D015313
10411803	323	340	hemolytic anemias	Disease	D000743
10411803	375	384	cefotetan	Chemical	D015313
10411803	482	498	hemolytic anemia	Disease	D000743
10411803	CID	D015313	D000743

10225068|t|Cauda equina syndrome after spinal anaesthesia with hyperbaric 5% lignocaine: a review of six cases of cauda equina syndrome reported to the Swedish Pharmaceutical Insurance 1993-1997.
10225068|a|Six cases of cauda equina syndrome with varying severity were reported to the Swedish Pharmaceutical Insurance during the period 1993-1997. All were associated with spinal anaesthesia using hyperbaric 5% lignocaine. Five cases had single-shot spinal anaesthesia and one had a repeat spinal anaesthetic due to inadequate block. The dose of hyperbaric 5% lignocaine administered ranged from 60 to 120 mg. Three of the cases were most likely caused by direct neurotoxicity of hyperbaric 5% lignocaine. In the other 3 cases, direct neurotoxicity was also probable, but unfortunately radiological investigations were not done to definitely exclude a compressive aetiology. All cases sustained permanent neurological deficits. We recommend that hyperbaric lignocaine should be administered in concentrations not greater than 2% and at a total dose preferably not exceeding 60 mg.
10225068	0	21	Cauda equina syndrome	Disease	D011128
10225068	66	76	lignocaine	Chemical	D008012
10225068	103	124	cauda equina syndrome	Disease	D011128
10225068	198	219	cauda equina syndrome	Disease	D011128
10225068	389	399	lignocaine	Chemical	D008012
10225068	538	548	lignocaine	Chemical	D008012
10225068	641	654	neurotoxicity	Disease	D020258
10225068	672	682	lignocaine	Chemical	D008012
10225068	713	726	neurotoxicity	Disease	D020258
10225068	883	904	neurological deficits	Disease	D009461
10225068	935	945	lignocaine	Chemical	D008012
10225068	CID	D008012	D011128

9549528|t|Cortical motor overactivation in parkinsonian patients with L-dopa-induced peak-dose dyskinesia.
9549528|a|We have studied the regional cerebral blood flow (rCBF) changes induced by the execution of a finger-to-thumb opposition motor task in the supplementary and primary motor cortex of two groups of parkinsonian patients on L-dopa medication, the first one without L-dopa induced dyskinesia (n = 23) and the other with moderate peak-dose dyskinesia (n = 15), and of a group of 14 normal subjects. Single photon emission tomography with i.v. 133Xe was used to measure the rCBF changes. The dyskinetic parkinsonian patients exhibited a pattern of response which was markedly different from those of the normal subjects and non-dyskinetic parkinsonian patients, with a significant overactivation in the supplementary motor area and the ipsi- and contralateral primary motor areas. These results are compatible with the hypothesis that an hyperkinetic abnormal involuntary movement, like L-dopa-induced peak dose dyskinesia, is due to a disinhibition of the primary and associated motor cortex secondary to an excessive outflow of the pallidothalamocortical motor loop.
9549528	33	45	parkinsonian	Disease	D020734
9549528	60	66	L-dopa	Chemical	D007980
9549528	85	95	dyskinesia	Disease	D004409
9549528	292	304	parkinsonian	Disease	D020734
9549528	317	323	L-dopa	Chemical	D007980
9549528	358	364	L-dopa	Chemical	D007980
9549528	373	383	dyskinesia	Disease	D004409
9549528	431	441	dyskinesia	Disease	D004409
9549528	582	592	dyskinetic	Disease	D004409
9549528	593	605	parkinsonian	Disease	D020734
9549528	718	728	dyskinetic	Disease	D004409
9549528	729	741	parkinsonian	Disease	D020734
9549528	928	940	hyperkinetic	Disease	D006948
9549528	941	970	abnormal involuntary movement	Disease	D004409
9549528	977	983	L-dopa	Chemical	D007980
9549528	1002	1012	dyskinesia	Disease	D004409
9549528	CID	D007980	D004409

7843916|t|Dexamethasone-induced ocular hypertension in perfusion-cultured human eyes.
7843916|a|PURPOSE: Glucocorticoid administration can lead to the development of ocular hypertension and corticosteroid glaucoma in a subset of the population through a decrease in the aqueous humor outflow facility. The purpose of this study was to determine whether glucocorticoid treatment can directly affect the outflow facility of isolated, perfusion-cultured human eyes. METHODS: The anterior segments of human donor eyes from regional eye banks were placed in a constant flow, variable pressure perfusion culture system. Paired eyes were perfused in serum-free media with or without 10(-7) M dexamethasone for 12 days. Intraocular pressure was monitored daily. After incubation, the eyes were morphologically characterized by light microscopy, transmission and scanning electron microscopy, and scanning laser confocal microscopy. RESULTS: A significant increase in intraocular pressure developed in 13 of the 44 pairs of eyes perfused with dexamethasone with an average pressure rise of 17.5 +/- 3.8 mm Hg after 12 days of dexamethasone exposure. The contralateral control eyes, which did not receive dexamethasone, maintained a stable intraocular pressure during the same period. The outflow pathway of the untreated eyes appeared morphologically normal. In contrast, the dexamethasone-treated hypertensive eyes had thickened trabecular beams, decreased intertrabecular spaces, thickened juxtacanalicular tissue, activated trabecular meshwork cells, and increased amounts of amorphogranular extracellular material, especially in the juxtacanalicular tissue and beneath the endothelial lining of the canal of Schlemm. The dexamethasone-treated nonresponder eyes appeared to be morphologically similar to the untreated eyes, although several subtle dexamethasone-induced morphologic changes were evident. CONCLUSION: Dexamethasone treatment of isolated, perfusion-cultured human eyes led to the generation of ocular hypertension in approximately 30% of the dexamethasone-treated eyes. Steroid treatment resulted in morphologic changes in the trabecular meshwork similar to those reported for corticosteroid glaucoma and open angle glaucoma. This system may provide an acute model in which to study the pathogenic mechanisms involved in steroid glaucoma and primary open angle glaucoma.
7843916	0	13	Dexamethasone	Chemical	D003907
7843916	22	41	ocular hypertension	Disease	D009798
7843916	146	165	ocular hypertension	Disease	D009798
7843916	170	193	corticosteroid glaucoma	Disease	D005901
7843916	665	678	dexamethasone	Chemical	D003907
7843916	1014	1027	dexamethasone	Chemical	D003907
7843916	1097	1110	dexamethasone	Chemical	D003907
7843916	1175	1188	dexamethasone	Chemical	D003907
7843916	1347	1360	dexamethasone	Chemical	D003907
7843916	1369	1386	hypertensive eyes	Disease	D009798
7843916	1696	1709	dexamethasone	Chemical	D003907
7843916	1822	1835	dexamethasone	Chemical	D003907
7843916	1890	1903	Dexamethasone	Chemical	D003907
7843916	1982	2001	ocular hypertension	Disease	D009798
7843916	2030	2043	dexamethasone	Chemical	D003907
7843916	2058	2065	Steroid	Chemical	D013256
7843916	2165	2188	corticosteroid glaucoma	Disease	D005901
7843916	2193	2212	open angle glaucoma	Disease	D005902
7843916	2309	2325	steroid glaucoma	Disease	D005901
7843916	2330	2357	primary open angle glaucoma	Disease	D005902
7843916	CID	D003907	D009798

7803371|t|Cognitive deterioration from long-term abuse of dextromethorphan: a case report.
7803371|a|Dextromethorphan (DM), the dextrorotatory isomer of 3-hydroxy-N-methylmorphinan, is the main ingredient in a number of widely available, over-the-counter antitussives. Initial studies (Bornstein 1968) showed that it possessed no respiratory suppressant effects and no addiction liability. Subsequently, however, several articles reporting abuse of this drug have appeared in the literature. The drug is known to cause a variety of acute toxic effects, ranging from nausea, restlessness, insomnia, ataxia, slurred speech and nystagmus to mood changes, perceptual alterations, inattention, disorientation and aggressive behavior (Rammer et al 1988; Katona and Watson 1986; Isbell and Fraser 1953; Devlin et al 1985; McCarthy 1971; Dodds and Revai 1967; Degkwitz 1964; Hildebrand et al 1989). There have also been two reported fatalities from DM overdoses (Fleming 1986). However, there are no reports describing the effects of chronic abuse. This report describes a case of cognitive deterioration resulting from prolonged use of DM.
7803371	0	23	Cognitive deterioration	Disease	D003072
7803371	48	64	dextromethorphan	Chemical	D003915
7803371	81	97	Dextromethorphan	Chemical	D003915
7803371	99	101	DM	Chemical	D003915
7803371	133	160	3-hydroxy-N-methylmorphinan	Chemical	D007981
7803371	546	552	nausea	Disease	D009325
7803371	554	566	restlessness	Disease	D011595
7803371	568	576	insomnia	Disease	D007319
7803371	578	584	ataxia	Disease	D001259
7803371	605	614	nystagmus	Disease	C564088
7803371	688	707	aggressive behavior	Disease	D001523
7803371	921	923	DM	Chemical	D003915
7803371	1053	1076	cognitive deterioration	Disease	D003072
7803371	1109	1111	DM	Chemical	D003915
7803371	CID	D003915	D003072

7437994|t|Long-term lithium treatment and the kidney. Interim report on fifty patients.
7437994|a|This is a report on the first part of our study of the effects of long-term lithium treatment on the kidney. Creatinine clearance, maximum urinary osmolality and 24 hour urine volume have been tested in 50 affectively ill patients who have been on long-term lithium for more than one year. These findings have been compared with norms and with values of the same tests from screening prior to lithium, available for most of our patients. No evidence was found for any reduction of glomerular filtration during lithium treatment. Low clearance values found in several patients could be accounted for by their age and their pre-lithium values. Urinary concentration defect appeared frequent but the extent of the impairment is difficult to assess because of the uncertainty about the norms applicable to this group of patients. The concentration defect appeared reversible, at least in part. Polyuria above 3 litres/24 hours was found in 10% of patients. An attempt is made to draw practical conclusions from the preliminary findings.
7437994	10	17	lithium	Chemical	D008094
7437994	154	161	lithium	Chemical	D008094
7437994	187	197	Creatinine	Chemical	D003404
7437994	336	343	lithium	Chemical	D008094
7437994	471	478	lithium	Chemical	D008094
7437994	588	595	lithium	Chemical	D008094
7437994	704	711	lithium	Chemical	D008094
7437994	968	976	Polyuria	Disease	D011141
7437994	CID	D008094	D011141

6496797|t|Complete heart block following a single dose of trazodone.
6496797|a|Forty minutes after receiving a single starting dose of trazodone, a patient developed complete heart block. The case illustrates that, despite the results of earlier studies, trazodone's effect on cardiac conduction may be severe in individuals at risk for conduction delay.
6496797	9	20	heart block	Disease	D006327
6496797	48	57	trazodone	Chemical	D014196
6496797	115	124	trazodone	Chemical	D014196
6496797	155	166	heart block	Disease	D006327
6496797	235	244	trazodone	Chemical	D014196
6496797	CID	D014196	D006327

3411101|t|Quinidine phenylethylbarbiturate-induced fulminant hepatitis in a pregnant woman. A case report.
3411101|a|We report the case of a 19-year-old Laotian patient affected by fulminant hepatitis during the third trimester of her pregnancy after a 1-month administration of quinidine phenylethylbarbiturate. After delivery, the patient underwent orthotopic liver transplantation. The patient was in good condition 16 months after liver transplantation. Quinidine itself or phenylethylbarbiturate may be responsible for fulminant hepatitis in this patient.
3411101	0	32	Quinidine phenylethylbarbiturate	Chemical	C033457
3411101	51	60	hepatitis	Disease	D056486
3411101	171	180	hepatitis	Disease	D056486
3411101	259	291	quinidine phenylethylbarbiturate	Chemical	C033457
3411101	438	447	Quinidine	Chemical	D011802
3411101	458	480	phenylethylbarbiturate	Chemical	C033457
3411101	514	523	hepatitis	Disease	D056486
3411101	CID	C033457	D056486

2598570|t|The epidemiology of the acute flank pain syndrome from suprofen.
2598570|a|Suprofen, a new nonsteroidal anti-inflammatory drug, was marketed in early 1986 as an analgesic agent. Until physicians began reporting an unusual acute flank pain syndrome to the spontaneous reporting system, 700,000 persons used the drug in the United States. Through August 1986, a total of 163 cases of this syndrome were reported. To elucidate the epidemiology of the syndrome, a case-control study was performed, comparing 62 of the case patients who had been reported to the spontaneous reporting system to 185 suprofen-exposed control subjects who did not have the syndrome. Case patients were more likely to be men (odds ratio, 3.8; 95% confidence interval, 1.2-12.1), suffer from hay fever and asthma (odds ratio, 3.4; 95% confidence interval, 1.0-11.9); to participate in regular exercise (odds ratio, 5.9; 95% confidence interval, 1.1-30.7), especially in the use of Nautilus equipment (p = 0.02); and to use alcohol (odds ratio, 4.4; 95% confidence interval, 1.1-17.5). Possible risk factors included young age, concurrent use of other analgesic agents (especially ibuprofen), preexisting renal disease, a history of kidney stones, a history of gout, a recent increase in activity, a recent increase in sun exposure, and residence in the Sunbelt. These were findings that were suggestive but did not reach conventional statistical significance. These findings are consistent with the postulated mechanism for this unusual syndrome: acute diffuse crystallization of uric acid in renal tubules.
2598570	30	40	flank pain	Disease	D021501
2598570	55	63	suprofen	Chemical	D013496
2598570	65	73	Suprofen	Chemical	D013496
2598570	218	228	flank pain	Disease	D021501
2598570	583	591	suprofen	Chemical	D013496
2598570	755	764	hay fever	Disease	D006255
2598570	769	775	asthma	Disease	D001249
2598570	986	993	alcohol	Chemical	D000431
2598570	1143	1152	ibuprofen	Chemical	D007052
2598570	1167	1180	renal disease	Disease	D007674
2598570	1195	1208	kidney stones	Disease	D007669
2598570	1223	1227	gout	Disease	D006073
2598570	1543	1552	uric acid	Chemical	D014527
2598570	CID	D013496	D021501

1415380|t|Hemolytic-uremic syndrome associated with ingestion of quinine.
1415380|a|Hemolytic-uremic syndrome following quinine ingestion is a newly described phenomenon, with just two previous descriptions of 4 cases in the literature. We describe a 5th case. The reaction may be mediated by the presence of antibodies reactive against platelets in the presence of quinine. Treatment has included use of plasma exchange, prednisone, aspirin, and dipyridamole. The patients have all regained some degree of renal function. However, it is unclear whether pharmacological treatment or spontaneous resolution is responsible for the improvement. Quinine-associated hemolytic-uremic syndrome probably occurs more often than is recognized. It is important to recognize this reaction when it occurs and to avoid further quinine exposure, since the reaction seems to be recurrent.
1415380	0	25	Hemolytic-uremic syndrome	Disease	D006463
1415380	55	62	quinine	Chemical	D011803
1415380	64	89	Hemolytic-uremic syndrome	Disease	D006463
1415380	100	107	quinine	Chemical	D011803
1415380	346	353	quinine	Chemical	D011803
1415380	402	412	prednisone	Chemical	D011241
1415380	414	421	aspirin	Chemical	D001241
1415380	427	439	dipyridamole	Chemical	D004176
1415380	622	629	Quinine	Chemical	D011803
1415380	641	666	hemolytic-uremic syndrome	Disease	D006463
1415380	793	800	quinine	Chemical	D011803
1415380	CID	D011803	D006463

1255900|t|Pyeloureteral filling defects associated with systemic anticoagulation: a case report.
1255900|a|The etiology of pyeloureteritis cystica has long been attributed to chronic infection and inflammation. A case is presented that is unique in that the acute onset and the rapid resolution of pyeloureteral filling defects in this patient were documented by radiography. There is no evidence of antecedent or concurrent infection in this patient. The disease occurred subsequent to the initiation of heparin therapy for suspected pelvic thrombophlebitis and cleared rapidly subsequent to its discontinuation. The rate of resolution of the radiographic findings may be helpful in distinguishing between true pyeloureteritis cystica and submucosal hemorrhage.
1255900	103	126	pyeloureteritis cystica	Disease	D011702
1255900	163	172	infection	Disease	D007239
1255900	177	189	inflammation	Disease	D007249
1255900	405	414	infection	Disease	D007239
1255900	485	492	heparin	Chemical	D006493
1255900	522	538	thrombophlebitis	Disease	D013924
1255900	692	715	pyeloureteritis cystica	Disease	D011702
1255900	720	741	submucosal hemorrhage	Disease	D006470
1255900	CID	D006493	D011702

85485|t|Changes in peroxisomes in preneoplastic liver and hepatoma of mice induced by alpha-benzene hexachloride.
85485|a|Peroxisomes in hepatomas and hyperplastic preneoplastic liver lesions induced in mice by 500 ppm alpha-benzene hexachloride were examined histochemically and electron microscopically. Although most of the hepatomas were well-differentiated tumors and contained a considerable number of peroxisomes, the tumor cells did not respond to ethyl-alpha-p-chlorophenoxyisobutyrate with proliferation of peroxisomes. At the 16th week of carcinogen feeding, hyperplastic nodules appeared and advanced to further stages. A majority of the nodules showed a considerable number of peroxisomes and the inductive proliferation of peroxisomes. Within the nodules, foci of proliferation of the cells that showed no inducibility of proliferation of peroxisomes appeared. These cells proliferated further, replacing the most part of the nodules, and with this process hepatomas appeared to have been formed. No abnormal matrical inclusions of peroxisomes were formed in the cells of hyperplastic nodules by ethyl-alpha-p-chlorophenoxyisobutyrate unlike in the case of rats.
85485	50	58	hepatoma	Disease	D006528
85485	78	104	alpha-benzene hexachloride	Chemical	D001556
85485	121	130	hepatomas	Disease	D006528
85485	162	175	liver lesions	Disease	D017093
85485	203	229	alpha-benzene hexachloride	Chemical	D001556
85485	311	320	hepatomas	Disease	D006528
85485	346	352	tumors	Disease	D009369
85485	409	414	tumor	Disease	D009369
85485	440	478	ethyl-alpha-p-chlorophenoxyisobutyrate	Chemical	C012282
85485	955	964	hepatomas	Disease	D006528
85485	1094	1132	ethyl-alpha-p-chlorophenoxyisobutyrate	Chemical	C012282
85485	CID	D001556	D006528

48362|t|Quinidine hepatitis.
48362|a|Long-term administration of quinidine was associated with persistent elevation of serum concentrations of SGOT, lactic acid dehydrogenase, and alkaline phosphatase. Liver biopsy showed active hepatitis. Discontinuance of quinidine therapy led to normalization of liver function tests. A challenge dose of quinidine caused clinical symptoms and abrupt elevation of SGOT, alkaline phosphatase, and lactic acid dehydrogenase values. We concluded that this patient had quinidine hepatotoxicity and believe that this is the first case reported with liver biopsy documentation. This report also suggests that, even after long-term administration, the hepatic toxicity is reversible.
48362	0	9	Quinidine	Chemical	D011802
48362	10	19	hepatitis	Disease	D056486
48362	49	58	quinidine	Chemical	D011802
48362	133	144	lactic acid	Chemical	D019344
48362	213	222	hepatitis	Disease	D056486
48362	242	251	quinidine	Chemical	D011802
48362	326	335	quinidine	Chemical	D011802
48362	417	428	lactic acid	Chemical	D019344
48362	486	495	quinidine	Chemical	D011802
48362	496	510	hepatotoxicity	Disease	D056486
48362	666	682	hepatic toxicity	Disease	D056486
48362	CID	D011802	D056486

9067481|t|Cholesteryl hemisuccinate treatment protects rodents from the toxic effects of acetaminophen, adriamycin, carbon tetrachloride, chloroform and galactosamine.
9067481|a|In addition to its use as a stabilizer/rigidifier of membranes, cholesteryl hemisuccinate, tris salt (CS) administration has also been shown to protect rats from the hepatotoxic effects of carbon tetrachloride (CCl4). To further our understanding of the mechanism of CS cytoprotection, we examined in rats and mice the protective abilities of CS and the non-hydrolyzable ether form of CS, gamma-cholesteryloxybutyric acid, tris salt (CSE) against acetaminophen-, adriamycin-, carbon tetrachloride-, chloroform- and galactosamine-induced toxicity. The results of these studies demonstrated that CS-mediated protection is not selective for a particular species, organ system or toxic chemical. A 24-h pretreatment of both rats and mice with a single dose of CS (100mg/kg, i.p.), resulted in significant protection against the hepatotoxic effects of CCl4, CHCl3, acetaminophen and galactosamine and against the lethal (and presumably cardiotoxic) effect of adriamycin administration. Maximal CS-mediated protection was observed in experimental animals pretreated 24 h prior to the toxic insult. These data suggest that CS intervenes in a critical cellular event that is an important common pathway to toxic cell death. The mechanism of CS protection does not appear to be dependent on the inhibition of chemical bioactivation to a toxic reactive intermediate (in light of the protection observed against galactosamine hepatotoxicity). However, based on the data presented, we can not exclude the possibility that CS administration inhibits chemical bioactivation. Our findings do suggest that CS-mediated protection is dependent on the action of the intact anionic CS molecule (non-hydrolyzable CSE was as protective as CS), whose mechanism has yet to be defined.
9067481	0	25	Cholesteryl hemisuccinate	Chemical	C013440
9067481	79	92	acetaminophen	Chemical	D000082
9067481	94	104	adriamycin	Chemical	D004317
9067481	106	126	carbon tetrachloride	Chemical	D002251
9067481	128	138	chloroform	Chemical	D002725
9067481	143	156	galactosamine	Chemical	D005688
9067481	222	247	cholesteryl hemisuccinate	Chemical	C013440
9067481	249	258	tris salt	Chemical	-1
9067481	260	262	CS	Chemical	-1
9067481	324	335	hepatotoxic	Disease	D056486
9067481	347	367	carbon tetrachloride	Chemical	D002251
9067481	369	373	CCl4	Chemical	D002251
9067481	425	427	CS	Chemical	-1
9067481	501	503	CS	Chemical	-1
9067481	543	545	CS	Chemical	-1
9067481	547	579	gamma-cholesteryloxybutyric acid	Chemical	C103872
9067481	581	590	tris salt	Chemical	-1
9067481	592	595	CSE	Chemical	-1
9067481	605	618	acetaminophen	Chemical	D000082
9067481	621	631	adriamycin	Chemical	D004317
9067481	634	654	carbon tetrachloride	Chemical	D002251
9067481	657	667	chloroform	Chemical	D002725
9067481	673	686	galactosamine	Chemical	D005688
9067481	695	703	toxicity	Disease	D064420
9067481	752	754	CS	Chemical	-1
9067481	914	916	CS	Chemical	-1
9067481	982	993	hepatotoxic	Disease	D056486
9067481	1005	1009	CCl4	Chemical	D002251
9067481	1011	1016	CHCl3	Chemical	D002725
9067481	1018	1031	acetaminophen	Chemical	D000082
9067481	1036	1049	galactosamine	Chemical	D005688
9067481	1089	1100	cardiotoxic	Disease	D066126
9067481	1112	1122	adriamycin	Chemical	D004317
9067481	1147	1149	CS	Chemical	-1
9067481	1274	1276	CS	Chemical	-1
9067481	1391	1393	CS	Chemical	-1
9067481	1559	1572	galactosamine	Chemical	D005688
9067481	1573	1587	hepatotoxicity	Disease	D056486
9067481	1668	1670	CS	Chemical	-1
9067481	1748	1750	CS	Chemical	-1
9067481	1820	1822	CS	Chemical	-1
9067481	1850	1853	CSE	Chemical	-1
9067481	1875	1877	CS	Chemical	-1
9067481	CID	D002251	D056486
9067481	CID	D002725	D056486
9067481	CID	D000082	D056486
9067481	CID	D005688	D056486
9067481	CID	D004317	D066126

19274460|t|DSMM XI study: dose definition for intravenous cyclophosphamide in combination with bortezomib/dexamethasone for remission induction in patients with newly diagnosed myeloma.
19274460|a|A clinical trial was initiated to evaluate the recommended dose of cyclophosphamide in combination with bortezomib and dexamethasone as induction treatment before stem cell transplantation for younger patients with newly diagnosed multiple myeloma (MM). Thirty patients were treated with three 21-day cycles of bortezomib 1.3 mg/m(2) on days 1, 4, 8, and 11 plus dexamethasone 40 mg on the day of bortezomib injection and the day after plus cyclophosphamide at 900, 1,200, or 1,500 mg/m(2) on day 1. The maximum tolerated dose of cyclophosphamide was defined as 900 mg/m(2). At this dose level, 92% of patients achieved at least a partial response. The overall response rate [complete response (CR) plus partial response (PR)] across all dose levels was 77%, with a 10% CR rate. No patient experienced progressive disease. The most frequent adverse events were hematological and gastrointestinal toxicities as well as neuropathy. The results suggest that bortezomib in combination with cyclophosphamide at 900 mg/m(2) and dexamethasone is an effective induction treatment for patients with newly diagnosed MM that warrants further investigation.
19274460	47	63	cyclophosphamide	Chemical	D003520
19274460	84	94	bortezomib	Chemical	C400082
19274460	95	108	dexamethasone	Chemical	D003907
19274460	166	173	myeloma	Disease	D009101
19274460	242	258	cyclophosphamide	Chemical	D003520
19274460	279	289	bortezomib	Chemical	C400082
19274460	294	307	dexamethasone	Chemical	D003907
19274460	406	422	multiple myeloma	Disease	D009101
19274460	424	426	MM	Disease	D009101
19274460	486	496	bortezomib	Chemical	C400082
19274460	538	551	dexamethasone	Chemical	D003907
19274460	572	582	bortezomib	Chemical	C400082
19274460	616	632	cyclophosphamide	Chemical	D003520
19274460	705	721	cyclophosphamide	Chemical	D003520
19274460	1036	1081	hematological and gastrointestinal toxicities	Disease	D006402|D005767	hematological toxicities|gastrointestinal toxicities
19274460	1093	1103	neuropathy	Disease	D009422
19274460	1130	1140	bortezomib	Chemical	C400082
19274460	1161	1177	cyclophosphamide	Chemical	D003520
19274460	1197	1210	dexamethasone	Chemical	D003907
19274460	1281	1283	MM	Disease	D009101
19274460	CID	D003907	D006402
19274460	CID	C400082	D005767
19274460	CID	D003520	D006402
19274460	CID	D003907	D005767
19274460	CID	C400082	D009422
19274460	CID	D003520	D005767
19274460	CID	C400082	D006402
19274460	CID	D003907	D009422
19274460	CID	D003520	D009422

18201582|t|Results of a comparative, phase III, 12-week, multicenter, prospective, randomized, double-blind assessment of the efficacy and tolerability of a fixed-dose combination of telmisartan and amlodipine versus amlodipine monotherapy in Indian adults with stage II hypertension.
18201582|a|OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerability of a new fixed-dose combination (FDC) of telmisartan 40 mg + amlodipine 5 mg (T+A) compared with amlodipine 5-mg monotherapy (A) in adult Indian patients with stage II hypertension. METHODS: This comparative, Phase III, 12-week, multicenter, prospective, randomized, double-blind study was conducted in Indian patients aged 18 to 65 years with established stage II hypertension. Patients were treated with oral FDC of T+A or A QD before breakfast for 12 weeks; blood pressure (BP) and heart rate were measured in the sitting position. Primary efficacy end points were reduction in clinical systolic BP (SBP)/ diastolic BP (DBP) from baseline to study end and number of responders (ie, patients who achieved target SBP/ DBP <130/<80 mm Hg) at end of study. Tolerability was assessed by treatment-emergent adverse events, identified using physical examination, laboratory analysis, and electrocardiography. RESULTS: A total of 210 patients were enrolled in the study; 203 patients (143 men, 60 women) completed the study while 7 were lost to follow-up (4 patients in the T+A group and 3 in the A group) and considered with-drawn. At study end, statistically significant percentage reductions from baseline within groups and between groups were observed in SBP (T+A [-27.4%]; A [-16.6%]) and DBP (T+A [-20.1%]; A [-13.3%]) (all, P < 0.05). Response rates were 87.3% (89/102) in the T+A group and 69.3% (70/101) in the A group (P < 0.05). The prevalences of adverse events were not significantly different between the 2 treatment groups (T+A, 16.0% [17/106]; A, 15.4% [16/104]). Peripheral edema was reported in 8.5% patients (9/106) in the T+A group compared with 13.5% (14/104) in the A group, and cough was reported in 3.8% patients (4/106) in the T+A group and 1.0% (1/104) patients in the A group; these differences did not reach statistical significance. The incidences of headache, dizziness, and diarrhea were similar between the 2 groups. CONCLUSIONS: Among these Indian patients with stage II hypertension, the FDC of T+A was found to be significantly more effective, with regard to BP reductions, than A, and both treatments were well tolerated.
18201582	172	183	telmisartan	Chemical	C084178
18201582	188	198	amlodipine	Chemical	D017311
18201582	206	216	amlodipine	Chemical	D017311
18201582	260	272	hypertension	Disease	D006973
18201582	394	405	telmisartan	Chemical	C084178
18201582	414	424	amlodipine	Chemical	D017311
18201582	450	460	amlodipine	Chemical	D017311
18201582	521	533	hypertension	Disease	D006973
18201582	718	730	hypertension	Disease	D006973
18201582	1939	1944	edema	Disease	D004487
18201582	2049	2054	cough	Disease	D003371
18201582	2228	2236	headache	Disease	D006261
18201582	2238	2247	dizziness	Disease	D004244
18201582	2253	2261	diarrhea	Disease	D003967
18201582	2352	2364	hypertension	Disease	D006973
18201582	CID	D017311	D006261
18201582	CID	C084178	D004244
18201582	CID	C084178	D006261
18201582	CID	C084178	D003967
18201582	CID	C084178	D004487
18201582	CID	D017311	D003967
18201582	CID	D017311	D004487
18201582	CID	D017311	D003371
18201582	CID	D017311	D004244
18201582	CID	C084178	D003371

11337188|t|Cutaneous leucocytoclastic vasculitis associated with oxacillin.
11337188|a|A 67-year-old man who was treated with oxacillin for one week because of Staphylococcus aureus bacteremia, developed renal failure and diffuse, symmetric, palpable purpuric lesions on his feet. Necrotic blisters were noted on his fingers. Skin biopsies showed findings diagnostic of leucocytoclastic vasculitis. Oxacillin was discontinued and patient was treated with corticosteroids. The rash disappeared after three weeks and renal function returned to normal. Leucocytoclastic vasculitis presents as palpable purpura of the lower extremities often accompanied by abdominal pain, arthralgia, and renal involvement. Etiologic factors or associated disorders include infections, medications, collagen vascular disease and neoplasia. However, in half of the cases no etiologic factor is identified. Usually it is a self-limited disorder, but corticosteroid therapy may be needed in life-threatening cases since early treatment with corticosteroids in severe cases can prevent complications. Oxacillin should be included among the drugs that can cause leucocytoclastic vasculitis.
11337188	0	37	Cutaneous leucocytoclastic vasculitis	Disease	D018366
11337188	54	63	oxacillin	Chemical	D010068
11337188	104	113	oxacillin	Chemical	D010068
11337188	138	170	Staphylococcus aureus bacteremia	Disease	D013203|D016470	Staphylococcus aureus bacteremia|bacteremia
11337188	182	195	renal failure	Disease	D051437
11337188	229	245	purpuric lesions	Disease	D011693
11337188	259	276	Necrotic blisters	Disease	D009336|D001768	Necrotic|blisters
11337188	348	375	leucocytoclastic vasculitis	Disease	D018366
11337188	377	386	Oxacillin	Chemical	D010068
11337188	433	448	corticosteroids	Chemical	D000305
11337188	454	458	rash	Disease	D005076
11337188	528	555	Leucocytoclastic vasculitis	Disease	D018366
11337188	577	584	purpura	Disease	D011693
11337188	631	645	abdominal pain	Disease	D015746
11337188	647	657	arthralgia	Disease	D018771
11337188	663	680	renal involvement	Disease	D007674
11337188	732	742	infections	Disease	D007239
11337188	757	782	collagen vascular disease	Disease	D003095
11337188	787	796	neoplasia	Disease	D009369
11337188	906	920	corticosteroid	Chemical	D000305
11337188	996	1011	corticosteroids	Chemical	D000305
11337188	1055	1064	Oxacillin	Chemical	D010068
11337188	1115	1142	leucocytoclastic vasculitis	Disease	D018366
11337188	CID	D000305	D051437
11337188	CID	D010068	D051437
11337188	CID	D010068	D018366
11337188	CID	D000305	D018366

6308526|t|Naloxazone pretreatment modifies cardiorespiratory, temperature, and behavioral effects of morphine.
6308526|a|Behavioral and cardiorespiratory responses to a lethal dose of morphine were evaluated in rats pretreated with saline or naloxazone, an antagonist of high-affinity mu 1 opioid receptors. Pretreatment with naloxazone significantly blocked morphine analgesia, catalepsy and hypothermia at a dose which completely eliminated high-affinity binding in brain membranes. Moreover, naloxazone significantly attenuated the morphine-induced hypotension and respiratory depression, whereas morphine-induced bradycardia was less affected. Results indicate that subpopulations of mu receptors may mediate selective behavioral and cardiorespiratory responses to morphine.
6308526	0	10	Naloxazone	Chemical	C024224
6308526	91	99	morphine	Chemical	D009020
6308526	164	172	morphine	Chemical	D009020
6308526	222	232	naloxazone	Chemical	C024224
6308526	306	316	naloxazone	Chemical	C024224
6308526	339	347	morphine	Chemical	D009020
6308526	348	357	analgesia	Disease	D000699
6308526	359	368	catalepsy	Disease	D002375
6308526	373	384	hypothermia	Disease	D007035
6308526	475	485	naloxazone	Chemical	C024224
6308526	515	523	morphine	Chemical	D009020
6308526	532	543	hypotension	Disease	D007022
6308526	548	570	respiratory depression	Disease	D012131
6308526	580	588	morphine	Chemical	D009020
6308526	597	608	bradycardia	Disease	D001919
6308526	749	757	morphine	Chemical	D009020
6308526	CID	D009020	D007022
6308526	CID	D009020	D007035
6308526	CID	D009020	D002375
6308526	CID	D009020	D001919

15897593|t|Dexrazoxane protects against myelosuppression from the DNA cleavage-enhancing drugs etoposide and daunorubicin but not doxorubicin.
15897593|a|PURPOSE: The anthracyclines daunorubicin and doxorubicin and the epipodophyllotoxin etoposide are potent DNA cleavage-enhancing drugs that are widely used in clinical oncology; however, myelosuppression and cardiac toxicity limit their use. Dexrazoxane (ICRF-187) is recommended for protection against anthracycline-induced cardiotoxicity. EXPERIMENTAL DESIGN: Because of their widespread use, the hematologic toxicity following coadministration of dexrazoxane and these three structurally different DNA cleavage enhancers was investigated: Sensitivity of human and murine blood progenitor cells to etoposide, daunorubicin, and doxorubicin +/- dexrazoxane was determined in granulocyte-macrophage colony forming assays. Likewise, in vivo, B6D2F1 mice were treated with etoposide, daunorubicin, and doxorubicin, with or without dexrazoxane over a wide range of doses: posttreatment, a full hematologic evaluation was done. RESULTS: Nontoxic doses of dexrazoxane reduced myelosuppression and weight loss from daunorubicin and etoposide in mice and antagonized their antiproliferative effects in the colony assay; however, dexrazoxane neither reduced myelosuppression, weight loss, nor the in vitro cytotoxicity from doxorubicin. CONCLUSION: Although our findings support the observation that dexrazoxane reduces neither hematologic activity nor antitumor activity from doxorubicin clinically, the potent antagonism of daunorubicin activity raises concern; a possible interference with anticancer efficacy certainly would call for renewed attention. Our data also suggest that significant etoposide dose escalation is perhaps possible by the use of dexrazoxane. Clinical trials in patients with brain metastases combining dexrazoxane and high doses of etoposide is ongoing with the aim of improving efficacy without aggravating hematologic toxicity. If successful, this represents an exciting mechanism for pharmacologic regulation of side effects from cytotoxic chemotherapy.
15897593	0	11	Dexrazoxane	Chemical	D064730
15897593	29	45	myelosuppression	Disease	D001855
15897593	84	93	etoposide	Chemical	D005047
15897593	98	110	daunorubicin	Chemical	D003630
15897593	119	130	doxorubicin	Chemical	D004317
15897593	145	159	anthracyclines	Chemical	D018943
15897593	160	172	daunorubicin	Chemical	D003630
15897593	177	188	doxorubicin	Chemical	D004317
15897593	197	215	epipodophyllotoxin	Chemical	D011034
15897593	216	225	etoposide	Chemical	D005047
15897593	318	334	myelosuppression	Disease	D001855
15897593	339	355	cardiac toxicity	Disease	D066126
15897593	373	384	Dexrazoxane	Chemical	D064730
15897593	386	394	ICRF-187	Chemical	D064730
15897593	434	447	anthracycline	Chemical	D018943
15897593	456	470	cardiotoxicity	Disease	D066126
15897593	530	550	hematologic toxicity	Disease	D006402
15897593	581	592	dexrazoxane	Chemical	D064730
15897593	731	740	etoposide	Chemical	D005047
15897593	742	754	daunorubicin	Chemical	D003630
15897593	760	771	doxorubicin	Chemical	D004317
15897593	776	787	dexrazoxane	Chemical	D064730
15897593	901	910	etoposide	Chemical	D005047
15897593	912	924	daunorubicin	Chemical	D003630
15897593	930	941	doxorubicin	Chemical	D004317
15897593	959	970	dexrazoxane	Chemical	D064730
15897593	1081	1092	dexrazoxane	Chemical	D064730
15897593	1101	1117	myelosuppression	Disease	D001855
15897593	1122	1133	weight loss	Disease	D015431
15897593	1139	1151	daunorubicin	Chemical	D003630
15897593	1156	1165	etoposide	Chemical	D005047
15897593	1252	1263	dexrazoxane	Chemical	D064730
15897593	1280	1296	myelosuppression	Disease	D001855
15897593	1298	1309	weight loss	Disease	D015431
15897593	1328	1340	cytotoxicity	Disease	D064420
15897593	1346	1357	doxorubicin	Chemical	D004317
15897593	1422	1433	dexrazoxane	Chemical	D064730
15897593	1499	1510	doxorubicin	Chemical	D004317
15897593	1548	1560	daunorubicin	Chemical	D003630
15897593	1718	1727	etoposide	Chemical	D005047
15897593	1778	1789	dexrazoxane	Chemical	D064730
15897593	1830	1840	metastases	Disease	D009362
15897593	1851	1862	dexrazoxane	Chemical	D064730
15897593	1881	1890	etoposide	Chemical	D005047
15897593	1957	1977	hematologic toxicity	Disease	D006402
15897593	CID	D003630	D015431
15897593	CID	D004317	D006402
15897593	CID	D005047	D006402
15897593	CID	D003630	D006402
15897593	CID	D005047	D015431
15897593	CID	D004317	D015431

6817363|t|Effects of the novel compound aniracetam (Ro 13-5057) upon impaired learning and memory in rodents.
6817363|a|The effect of aniracetam (Ro 13-5057, 1-anisoyl-2-pyrrolidinone) was studied on various forms of experimentally impaired cognitive functions (learning and memory) in rodents and produced the following effects: (1) almost complete prevention of the incapacity to learn a discrete escape response in rats exposed to sublethal hypercapnia immediately before the acquisition session; (2) partial (rats) or complete (mice) prevention of the scopolamine-induced short-term amnesia for a passive avoidance task; (3) complete protection against amnesia for a passive avoidance task in rats submitted to electroconvulsive shock immediately after avoidance acquisition; (4) prevention of the long-term retention- or retrieval-deficit for a passive avoidance task induced in rats and mice by chloramphenicol or cycloheximide administered immediately after acquisition; (5) reversal, when administered as late as 1 h before the retention test, of the deficit in retention or retrieval of a passive avoidance task induced by cycloheximide injected 2 days previously; (6) prevention of the deficit in the retrieval of an active avoidance task induced in mice by subconvulsant electroshock or hypercapnia applied immediately before retrieval testing (24 h after acquisition). These improvements or normalizations of impaired cognitive functions were seen at oral aniracetam doses of 10-100 mg/kg. Generally, the dose-response curves were bell-shaped. The mechanisms underlying the activity of aniracetam and its 'therapeutic window' are unknown. Piracetam, another pyrrolidinone derivative was used for comparison. It was active only in six of nine tests and had about one-tenth the potency of aniracetam. The results indicate that aniracetam improves cognitive functions which are impaired by different procedure and in different phases of the learning and memory process.
6817363	30	40	aniracetam	Chemical	C036466
6817363	42	52	Ro 13-5057	Chemical	C036466
6817363	59	87	impaired learning and memory	Disease	D007859|D008569	impaired learning|impaired memory
6817363	114	124	aniracetam	Chemical	C036466
6817363	126	136	Ro 13-5057	Chemical	C036466
6817363	138	163	1-anisoyl-2-pyrrolidinone	Chemical	C036466
6817363	212	240	impaired cognitive functions	Disease	D003072
6817363	424	435	hypercapnia	Disease	D006935
6817363	536	547	scopolamine	Chemical	D012601
6817363	567	574	amnesia	Disease	D000647
6817363	637	644	amnesia	Disease	D000647
6817363	881	896	chloramphenicol	Chemical	D002701
6817363	900	913	cycloheximide	Chemical	D003513
6817363	1112	1125	cycloheximide	Chemical	D003513
6817363	1278	1289	hypercapnia	Disease	D006935
6817363	1401	1429	impaired cognitive functions	Disease	D003072
6817363	1448	1458	aniracetam	Chemical	C036466
6817363	1578	1588	aniracetam	Chemical	C036466
6817363	1631	1640	Piracetam	Chemical	D010889
6817363	1650	1663	pyrrolidinone	Chemical	D011760
6817363	1779	1789	aniracetam	Chemical	C036466
6817363	1817	1827	aniracetam	Chemical	C036466
6817363	CID	D012601	D000647
6817363	CID	D003513	D008569
6817363	CID	D002701	D008569

11900788|t|Nicotine potentiation of morphine-induced catalepsy in mice.
11900788|a|In the present study, effects of nicotine on catalepsy induced by morphine in mice have been investigated. Morphine but not nicotine induced a dose-dependent catalepsy. The response of morphine was potentiated by nicotine. Intraperitoneal administration of atropine, naloxone, mecamylamine, and hexamethonium to mice reduced catalepsy induced by a combination of morphine with nicotine. Intracerebroventricular injection of atropine, hexamethonium, and naloxone also decreased catalepsy induced by morphine plus nicotine. Intraperitoneal administration of atropine, but not intraperitoneal or intracerebroventricular injection of hexamethonium, decreased the effect of a single dose of morphine. It was concluded that morphine catalepsy can be elicited by opioid and cholinergic receptors, and the potentiation of morphine induced by nicotine may also be mediated through cholinergic receptor mechanisms.
11900788	0	8	Nicotine	Chemical	D009538
11900788	25	33	morphine	Chemical	D009020
11900788	42	51	catalepsy	Disease	D002375
11900788	94	102	nicotine	Chemical	D009538
11900788	106	115	catalepsy	Disease	D002375
11900788	127	135	morphine	Chemical	D009020
11900788	168	176	Morphine	Chemical	D009020
11900788	185	193	nicotine	Chemical	D009538
11900788	219	228	catalepsy	Disease	D002375
11900788	246	254	morphine	Chemical	D009020
11900788	274	282	nicotine	Chemical	D009538
11900788	318	326	atropine	Chemical	D001285
11900788	328	336	naloxone	Chemical	D009270
11900788	338	350	mecamylamine	Chemical	D008464
11900788	356	369	hexamethonium	Chemical	D018738
11900788	386	395	catalepsy	Disease	D002375
11900788	424	432	morphine	Chemical	D009020
11900788	438	446	nicotine	Chemical	D009538
11900788	485	493	atropine	Chemical	D001285
11900788	495	508	hexamethonium	Chemical	D018738
11900788	514	522	naloxone	Chemical	D009270
11900788	538	547	catalepsy	Disease	D002375
11900788	559	567	morphine	Chemical	D009020
11900788	573	581	nicotine	Chemical	D009538
11900788	617	625	atropine	Chemical	D001285
11900788	691	704	hexamethonium	Chemical	D018738
11900788	747	755	morphine	Chemical	D009020
11900788	779	787	morphine	Chemical	D009020
11900788	788	797	catalepsy	Disease	D002375
11900788	875	883	morphine	Chemical	D009020
11900788	895	903	nicotine	Chemical	D009538
11900788	CID	D009020	D002375
11900788	CID	D009538	D002375

11230490|t|Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer.
11230490|a|PURPOSE: To determine whether Myocet (liposome-encapsulated doxorubicin; The Liposome Company, Elan Corporation, Princeton, NJ) in combination with cyclophosphamide significantly reduces doxorubicin cardiotoxicity while providing comparable antitumor efficacy in first-line treatment of metastatic breast cancer (MBC). PATIENTS AND METHODS: Two hundred ninety-seven patients with MBC and no prior chemotherapy for metastatic disease were randomized to receive either 60 mg/m(2) of Myocet (M) or conventional doxorubicin (A), in combination with 600 mg/m(2) of cyclophosphamide (C), every 3 weeks until disease progression or unacceptable toxicity. Cardiotoxicity was defined by reductions in left-ventricular ejection fraction, assessed by serial multigated radionuclide angiography scans, or congestive heart failure (CHF). Antitumor efficacy was assessed by objective tumor response rates (World Health Organization criteria), time to progression, and survival. RESULTS: Six percent of MC patients versus 21% (including five cases of CHF) of AC patients developed cardiotoxicity (P =.0002). Median cumulative doxorubicin dose at onset was more than 2,220 mg/m(2) for MC versus 480 mg/m(2) for AC (P =.0001, hazard ratio, 5.04). MC patients also experienced less grade 4 neutropenia. Antitumor efficacy of MC versus AC was comparable: objective response rates, 43% versus 43%; median time to progression, 5.1% versus 5.5 months; median time to treatment failure, 4.6 versus 4.4 months; and median survival, 19 versus 16 months. CONCLUSION: Myocet improves the therapeutic index of doxorubicin by significantly reducing cardiotoxicity and grade 4 neutropenia and provides comparable antitumor efficacy, when used in combination with cyclophosphamide as first-line therapy for MBC.
11230490	8	22	cardiotoxicity	Disease	D066126
11230490	81	92	doxorubicin	Chemical	D004317
11230490	97	113	cyclophosphamide	Chemical	D003520
11230490	141	152	doxorubicin	Chemical	D004317
11230490	157	173	cyclophosphamide	Chemical	D003520
11230490	223	236	breast cancer	Disease	D001943
11230490	268	274	Myocet	Chemical	D004317
11230490	298	309	doxorubicin	Chemical	D004317
11230490	386	402	cyclophosphamide	Chemical	D003520
11230490	425	436	doxorubicin	Chemical	D004317
11230490	437	451	cardiotoxicity	Disease	D066126
11230490	536	549	breast cancer	Disease	D001943
11230490	551	554	MBC	Disease	D001943
11230490	618	621	MBC	Disease	D001943
11230490	719	725	Myocet	Chemical	D004317
11230490	746	757	doxorubicin	Chemical	D004317
11230490	798	814	cyclophosphamide	Chemical	D003520
11230490	876	884	toxicity	Disease	D064420
11230490	886	900	Cardiotoxicity	Disease	D066126
11230490	1031	1055	congestive heart failure	Disease	D006333
11230490	1057	1060	CHF	Disease	D006333
11230490	1108	1113	tumor	Disease	D009369
11230490	1274	1277	CHF	Disease	D006333
11230490	1304	1318	cardiotoxicity	Disease	D066126
11230490	1349	1360	doxorubicin	Chemical	D004317
11230490	1510	1521	neutropenia	Disease	D009503
11230490	1779	1785	Myocet	Chemical	D004317
11230490	1820	1831	doxorubicin	Chemical	D004317
11230490	1858	1872	cardiotoxicity	Disease	D066126
11230490	1885	1896	neutropenia	Disease	D009503
11230490	1971	1987	cyclophosphamide	Chemical	D003520
11230490	2014	2017	MBC	Disease	D001943
11230490	CID	D003520	D009503
11230490	CID	D004317	D009503
11230490	CID	D003520	D006333
11230490	CID	D004317	D006333

2594614|t|Protective effect of a specific platelet-activating factor antagonist, BN 52021, on bupivacaine-induced cardiovascular impairments in rats.
2594614|a|Administration of the local anaesthetic bupivacaine (1.5 or 2 mg/kg, i.v.) to rats elicited a marked decrease of mean arterial blood pressure (MBP) and heart rate (HR) leading to death (in 67% or 90% of animals respectively). Intravenous injection of the specific platelet-activating factor (PAF) antagonist BN 52021 (10 mg/kg), 30 min before bupivacaine administration (2 mg/kg i.v.) suppressed both the decrease of MBP and HR. In contrast, doses of 1 mg/kg BN 52021 given 30 min before or 10 mg/kg administered 5 min before i.v. injection of bupivacaine were ineffective. When BN 52021 (20 mg/kg i.v.) was injected immediately after bupivacaine (2 mg/kg), a partial reversion of the decrease of MBP and HR was observed, whereas the dose of 10 mg/kg was ineffective. A partial recovery of bupivacaine-induced ECG alterations was observed after pretreatment of the rats with BN 52021. Since the administration of BN 52021, at all doses studied, did not alter MBP and HR at the doses used, the bulk of these results clearly demonstrate a protective action of BN 52021, a specific antagonist of PAF, against bupivacaine-induced cardiovascular toxicity. Thus, consistent with its direct effect on heart, PAF appears to be implicated in bupivacaine-induced cardiovascular alterations.
2594614	71	79	BN 52021	Chemical	C045856
2594614	84	95	bupivacaine	Chemical	D002045
2594614	104	130	cardiovascular impairments	Disease	D002318
2594614	180	191	bupivacaine	Chemical	D002045
2594614	241	307	decrease of mean arterial blood pressure (MBP) and heart rate (HR)	Disease	D007022|D001919	decrease of mean arterial blood pressure (MBP)|decrease of heart rate (HR)
2594614	448	456	BN 52021	Chemical	C045856
2594614	483	494	bupivacaine	Chemical	D002045
2594614	545	567	decrease of MBP and HR	Disease	D007022|D001919	decrease of MBP|decrease of HR
2594614	599	607	BN 52021	Chemical	C045856
2594614	684	695	bupivacaine	Chemical	D002045
2594614	719	727	BN 52021	Chemical	C045856
2594614	775	786	bupivacaine	Chemical	D002045
2594614	825	847	decrease of MBP and HR	Disease	D007022|D001919	decrease of MBP|decrease of HR
2594614	930	941	bupivacaine	Chemical	D002045
2594614	1015	1023	BN 52021	Chemical	C045856
2594614	1053	1061	BN 52021	Chemical	C045856
2594614	1198	1206	BN 52021	Chemical	C045856
2594614	1246	1257	bupivacaine	Chemical	D002045
2594614	1266	1289	cardiovascular toxicity	Disease	D002318
2594614	1373	1384	bupivacaine	Chemical	D002045
2594614	1393	1419	cardiovascular alterations	Disease	D018376
2594614	CID	D002045	D001919
2594614	CID	D002045	D007022

2257294|t|Benzylacyclouridine reverses azidothymidine-induced marrow suppression without impairment of anti-human immunodeficiency virus activity.
2257294|a|Increased extracellular concentrations of uridine (Urd) have been reported to reduce, in vitro, azidothymidine (AZT)-induced inhibition of human granulocyte-macrophage progenitor cells without impairment of its antihuman immunodeficiency virus (HIV) activity. Because of the clinical toxicities associated with chronic Urd administration, the ability of benzylacyclouridine (BAU) to effect, in vivo, AZT-induced anemia and leukopenia was assessed. This agent inhibits Urd catabolism and, in vivo, increases the plasma concentration of Urd in a dose-dependent manner, without Urd-related toxicity. In mice rendered anemic and leukopenic by the administration of AZT for 28 days in drinking water (1.5 mg/mL), the continued administration of AZT plus daily BAU (300 mg/kg, orally) partially reversed AZT-induced anemia and leukopenia (P less than .05), increased peripheral reticulocytes (to 4.9%, P less than .01), increased cellularity in the marrow, and improved megaloblastosis. When coadministered with AZT from the onset of drug administration, BAU reduced AZT-induced marrow toxicity. In vitro, at a concentration of 100 mumol/L, BAU possesses minimal anti-HIV activity and has no effect on the ability of AZT to reverse the HIV-induced cytopathic effect in MT4 cells. The clinical and biochemical implications of these findings are discussed.
2257294	0	19	Benzylacyclouridine	Chemical	C034753
2257294	29	43	azidothymidine	Chemical	D015215
2257294	52	70	marrow suppression	Disease	D001855
2257294	104	120	immunodeficiency	Disease	D007153
2257294	179	186	uridine	Chemical	D014529
2257294	188	191	Urd	Chemical	D014529
2257294	233	247	azidothymidine	Chemical	D015215
2257294	249	252	AZT	Chemical	D015215
2257294	358	374	immunodeficiency	Disease	D007153
2257294	421	431	toxicities	Disease	D064420
2257294	456	459	Urd	Chemical	D014529
2257294	491	510	benzylacyclouridine	Chemical	C034753
2257294	512	515	BAU	Chemical	C034753
2257294	537	540	AZT	Chemical	D015215
2257294	549	555	anemia	Disease	D000740
2257294	560	570	leukopenia	Disease	D007970
2257294	605	608	Urd	Chemical	D014529
2257294	672	675	Urd	Chemical	D014529
2257294	712	715	Urd	Chemical	D014529
2257294	724	732	toxicity	Disease	D064420
2257294	751	757	anemic	Disease	D000740
2257294	762	772	leukopenic	Disease	D007970
2257294	798	801	AZT	Chemical	D015215
2257294	877	880	AZT	Chemical	D015215
2257294	892	895	BAU	Chemical	C034753
2257294	935	938	AZT	Chemical	D015215
2257294	947	953	anemia	Disease	D000740
2257294	958	968	leukopenia	Disease	D007970
2257294	1101	1116	megaloblastosis	Disease	-1
2257294	1143	1146	AZT	Chemical	D015215
2257294	1186	1189	BAU	Chemical	C034753
2257294	1198	1201	AZT	Chemical	D015215
2257294	1210	1225	marrow toxicity	Disease	D001855
2257294	1272	1275	BAU	Chemical	C034753
2257294	1348	1351	AZT	Chemical	D015215
2257294	CID	D015215	D001855
2257294	CID	D015215	D000740
2257294	CID	D015215	D007970

10840460|t|Cyclophosphamide-induced cystitis in freely-moving conscious rats: behavioral approach to a new model of visceral pain.
10840460|a|PURPOSE: To develop a model of visceral pain in rats using a behavioral approach. Cyclophosphamide (CP), an antitumoral agent known to produce toxic effects on the bladder wall through its main toxic metabolite acrolein, was used to induce cystitis. MATERIALS AND METHODS: CP was administered at doses of 50, 100 and 200 mg./kg. i.p. to male rats, and their behavior observed and scored. The effects of morphine (0.5 to 4 mg./kg. i.v.) on CP-induced behavioral modifications were tested administered alone and after naloxone (1 mg./kg. s.c.). In addition, 90 minutes after CP injection, that is, at the time of administration of morphine, the bladder was removed in some rats for histological examination. Finally, to show that the bladder is essential for the CP-induced behavioral modifications, female rats also received CP at doses of 200 mg./kg. i.p. and of 20 mg. by the intravesical route, and acrolein at doses of 0.5 mg. by the intravesical route and of 5 mg./kg. i.v. RESULTS: CP dose-relatedly induced marked behavioral modifications in male rats: breathing rate decrease, closing of the eyes and occurrence of specific postures. Morphine dose-dependently reversed these behavioral disorders. A dose of 0.5 mg./kg. produced a reduction of almost 50% of the behavioral score induced by CP 200 mg./kg. This effect was completely prevented by pretreatment with naloxone. At the time of administration of morphine, histological modifications of the bladder wall, such as chorionic and muscle layer edema, were observed. In female rats, CP 200 mg./kg. i.p. produced the same marked behavioral modifications as those observed in male rats. Administered at the dose of 20 mg. intravesically, CP did not produce any behavioral effects, whereas acrolein at 0.5 mg. intravesically induced behavioral modifications identical to those under CP 200 mg./kg. i.p., with the same maximal levels. Conversely, acrolein 5 mg./kg. i.v. did not produce any behavioral effects at all. CONCLUSIONS: Overall, these results indicate that this experimental model of CP-induced cystitis may be an interesting new behavioral model of inflammatory visceral pain, allowing a better understanding of these painful syndromes and thus a better therapeutic approach to them.
10840460	0	16	Cyclophosphamide	Chemical	D003520
10840460	25	33	cystitis	Disease	D003556
10840460	105	118	visceral pain	Disease	D059265
10840460	151	164	visceral pain	Disease	D059265
10840460	202	218	Cyclophosphamide	Chemical	D003520
10840460	220	222	CP	Chemical	D003520
10840460	331	339	acrolein	Chemical	D000171
10840460	360	368	cystitis	Disease	D003556
10840460	393	395	CP	Chemical	D003520
10840460	523	531	morphine	Chemical	D009020
10840460	559	561	CP	Chemical	D003520
10840460	636	644	naloxone	Chemical	D009270
10840460	693	695	CP	Chemical	D003520
10840460	749	757	morphine	Chemical	D009020
10840460	881	883	CP	Chemical	D003520
10840460	944	946	CP	Chemical	D003520
10840460	1021	1029	acrolein	Chemical	D000171
10840460	1107	1109	CP	Chemical	D003520
10840460	1261	1269	Morphine	Chemical	D009020
10840460	1302	1322	behavioral disorders	Disease	D001523
10840460	1416	1418	CP	Chemical	D003520
10840460	1489	1497	naloxone	Chemical	D009270
10840460	1532	1540	morphine	Chemical	D009020
10840460	1625	1630	edema	Disease	D004487
10840460	1663	1665	CP	Chemical	D003520
10840460	1816	1818	CP	Chemical	D003520
10840460	1867	1875	acrolein	Chemical	D000171
10840460	1960	1962	CP	Chemical	D003520
10840460	2023	2031	acrolein	Chemical	D000171
10840460	2171	2173	CP	Chemical	D003520
10840460	2182	2190	cystitis	Disease	D003556
10840460	2250	2263	visceral pain	Disease	D059265
10840460	2306	2323	painful syndromes	Disease	D010146
10840460	CID	D003520	D003556
10840460	CID	D003520	D010146
10840460	CID	D000171	D010146

8278214|t|Hyperalgesia and myoclonus in terminal cancer patients treated with continuous intravenous morphine.
8278214|a|Eight cancer patients in the terminal stages of the disease treated with high doses of intravenous morphine developed hyperalgesia. All cases were retrospectively sampled from three different hospitals in Copenhagen. Five patients developed universal hyperalgesia and hyperesthesia which in 2 cases were accompanied by myoclonus. In 3 patients a pre-existing neuralgia increased to excruciating intensity and in 2 of these cases myoclonus occurred simultaneously. Although only few clinical descriptions of the relationship between hyperalgesia/myoclonus and high doses of morphine are available, experimental support from animal studies indicates that morphine, or its metabolites, plays a causative role for the observed behavioural syndrome. The possible mechanisms are discussed and treatment proposals given suggesting the use of more efficacious opioids with less excitatory potency in these situations.
8278214	0	12	Hyperalgesia	Disease	D006930
8278214	17	26	myoclonus	Disease	D009207
8278214	39	45	cancer	Disease	D009369
8278214	91	99	morphine	Chemical	D009020
8278214	107	113	cancer	Disease	D009369
8278214	200	208	morphine	Chemical	D009020
8278214	219	231	hyperalgesia	Disease	D006930
8278214	352	364	hyperalgesia	Disease	D006930
8278214	369	382	hyperesthesia	Disease	D006941
8278214	420	429	myoclonus	Disease	D009207
8278214	460	469	neuralgia	Disease	D009437
8278214	530	539	myoclonus	Disease	D009207
8278214	633	645	hyperalgesia	Disease	D006930
8278214	646	655	myoclonus	Disease	D009207
8278214	674	682	morphine	Chemical	D009020
8278214	754	762	morphine	Chemical	D009020
8278214	CID	D009020	D006930
8278214	CID	D009020	D006941
8278214	CID	D009020	D009437
8278214	CID	D009020	D009207

3934126|t|A prospective study of adverse reactions associated with vancomycin therapy.
3934126|a|A prospective evaluation of the efficacy and safety of vancomycin was conducted in 54 consecutive patients over a 16-month period. Vancomycin was curative in 95% of 43 patients with proven infection. Drugs were ceased in six patients because of adverse reactions; in three of these vancomycin was considered the likely cause. Reactions included thrombophlebitis (20 of 54 patients), rash (4 of 54), nephrotoxicity (4 of 50), proteinuria (1 of 50) and ototoxicity (1 of 11 patients tested by audiometry). Thrombophlebitis occurred only with infusion through peripheral cannulae; nephrotoxicity and ototoxicity were confined to patients receiving an aminoglycoside plus vancomycin. We conclude that vancomycin, administered appropriately, constitutes safe, effective therapy for infections caused by susceptible bacteria.
3934126	57	67	vancomycin	Chemical	D014640
3934126	132	142	vancomycin	Chemical	D014640
3934126	208	218	Vancomycin	Chemical	D014640
3934126	266	275	infection	Disease	D007239
3934126	359	369	vancomycin	Chemical	D014640
3934126	422	438	thrombophlebitis	Disease	D013924
3934126	460	464	rash	Disease	D005076
3934126	476	490	nephrotoxicity	Disease	D007674
3934126	502	513	proteinuria	Disease	D011507
3934126	528	539	ototoxicity	Disease	D006311
3934126	581	597	Thrombophlebitis	Disease	D013924
3934126	655	669	nephrotoxicity	Disease	D007674
3934126	674	685	ototoxicity	Disease	D006311
3934126	725	739	aminoglycoside	Chemical	D000617
3934126	745	755	vancomycin	Chemical	D014640
3934126	774	784	vancomycin	Chemical	D014640
3934126	854	864	infections	Disease	D007239
3934126	CID	D014640	D013924
3934126	CID	D014640	D005076
3934126	CID	D014640	D011507
3934126	CID	D014640	D006311

1687392|t|Blockade of both D-1 and D-2 dopamine receptors may induce catalepsy in mice.
1687392|a|1. The catalepsy induced by dopamine antagonists has been tested and the possible dopamine subtypes involved in catalepsy was determined. 2. Dopamine antagonist fluphenazine, D-1 antagonist SCH 23390 or D-2 antagonist sulpiride induced catalepsy. The effect of fluphenazine and sulpiride was dose-dependent. Combination of SCH 23390 with sulpiride did not induce catalepsy potentiation. 3. D-1 agonist SKF 38393 or D-2 agonist quinpirole decreased the catalepsy induced by fluphenazine, SCH 23390 or sulpiride. 4. Combination of SKF 38393 with quinpirole did not cause potentiated inhibitory effect on catalepsy induced by dopamine antagonists. 5. The data may indicate that although D-2 receptor blockade is involved in catalepsy, the D-1 receptor may plan a role.
1687392	29	37	dopamine	Chemical	D004298
1687392	59	68	catalepsy	Disease	D002375
1687392	85	94	catalepsy	Disease	D002375
1687392	106	114	dopamine	Chemical	D004298
1687392	160	168	dopamine	Chemical	D004298
1687392	190	199	catalepsy	Disease	D002375
1687392	219	227	Dopamine	Chemical	D004298
1687392	239	251	fluphenazine	Chemical	D005476
1687392	268	277	SCH 23390	Chemical	C534628
1687392	296	305	sulpiride	Chemical	D013469
1687392	314	323	catalepsy	Disease	D002375
1687392	339	351	fluphenazine	Chemical	D005476
1687392	356	365	sulpiride	Chemical	D013469
1687392	401	410	SCH 23390	Chemical	C534628
1687392	416	425	sulpiride	Chemical	D013469
1687392	441	450	catalepsy	Disease	D002375
1687392	480	489	SKF 38393	Chemical	D015647
1687392	505	515	quinpirole	Chemical	D019257
1687392	530	539	catalepsy	Disease	D002375
1687392	551	563	fluphenazine	Chemical	D005476
1687392	565	574	SCH 23390	Chemical	C534628
1687392	578	587	sulpiride	Chemical	D013469
1687392	607	616	SKF 38393	Chemical	D015647
1687392	622	632	quinpirole	Chemical	D019257
1687392	680	689	catalepsy	Disease	D002375
1687392	701	709	dopamine	Chemical	D004298
1687392	799	808	catalepsy	Disease	D002375
1687392	CID	D005476	D002375
1687392	CID	D013469	D002375
1687392	CID	C534628	D002375

19719056|t|Dextran-etodolac conjugates: synthesis, in vitro and in vivo evaluation.
19719056|a|Etodolac (E), is a non-narcotic analgesic and antiinflammatory drug. A biodegradable polymer dextran has been utilized as a carrier for synthesis of etodolac-dextran conjugates (ED) to improve its aqueous solubility and reduce gastrointestinal side effects. An activated moiety, i.e. N-acylimidazole derivative of etodolac (EAI), was condensed with the polysaccharide polymer dextran of different molecular weights (40000, 60000, 110000 and 200000). IR spectral data confirmed formation of ester bonding in the conjugates. Etodolac contents were evaluated by UV-spectrophotometric analysis. The molecular weights were determined by measuring viscosity using the Mark-Howink-Sakurada equation. In vitro hydrolysis of ED was done in aqueous buffers (pH 1.2, 7.4, 9) and in 80% (v/v) human plasma (pH 7.4). At pH 9, a higher rate of etodolac release from ED was observed as compared to aqueous buffer of pH 7.4 and 80% human plasma (pH 7.4), following first-order kinetics. In vivo investigations were performed in animals. Acute analgesic and antiinflammatory activities were ascertained using acetic acid induced writhing model (mice) and carrageenan-induced rat paw edema model, respectively. In comparison to control, E and ED1-ED4 showed highly significant analgesic and antiinflammatory activities (p <0.001). Biological evaluation suggested that conjugates (ED1-ED4) retained comparable analgesic and antiinflammatory activities with remarkably reduced ulcerogenicity as compared to their parent drug--etodolac.
19719056	0	7	Dextran	Chemical	D003911
19719056	8	16	etodolac	Chemical	D017308
19719056	73	81	Etodolac	Chemical	D017308
19719056	83	84	E	Chemical	D017308
19719056	166	173	dextran	Chemical	D003911
19719056	222	230	etodolac	Chemical	D017308
19719056	231	238	dextran	Chemical	D003911
19719056	357	372	N-acylimidazole	Chemical	-1
19719056	387	395	etodolac	Chemical	D017308
19719056	397	400	EAI	Chemical	-1
19719056	449	456	dextran	Chemical	D003911
19719056	596	604	Etodolac	Chemical	D017308
19719056	903	911	etodolac	Chemical	D017308
19719056	1165	1176	acetic acid	Chemical	D019342
19719056	1185	1193	writhing	Disease	D010146
19719056	1211	1222	carrageenan	Chemical	D002351
19719056	1239	1244	edema	Disease	D004487
19719056	1292	1293	E	Chemical	D017308
19719056	1579	1587	etodolac	Chemical	D017308
19719056	CID	D002351	D004487
19719056	CID	D002351	D010146

15266362|t|Hypersensitivity myocarditis complicating hypertrophic cardiomyopathy heart.
15266362|a|The present report describes a case of eosinophilic myocarditis complicating hypertrophic cardiomyopathy. The 47-year-old female patient, known to have hypertrophic cardiomyopathy, was admitted with biventricular failure and managed aggressively with dobutamine infusion and other drugs while being assessed for heart transplantation. On transthoracic echocardiogram, she had moderate left ventricular dysfunction with regional variability and moderate mitral regurgitation. The recipient's heart showed the features of apical hypertrophic cardiomyopathy and myocarditis with abundant eosinophils. Myocarditis is rare and eosinophilic myocarditis is rarer. It is likely that the hypersensitivity (eosinophilic) myocarditis was related to dobutamine infusion therapy. Eosinophilic myocarditis has been reported with an incidence of 2.4% to 7.2% in explanted hearts and may be related to multidrug therapy.
15266362	0	16	Hypersensitivity	Disease	D004342
15266362	17	28	myocarditis	Disease	D009205
15266362	42	69	hypertrophic cardiomyopathy	Disease	D002312
15266362	116	140	eosinophilic myocarditis	Disease	D004802|D009205	eosinophilic|myocarditis
15266362	154	181	hypertrophic cardiomyopathy	Disease	D002312
15266362	229	256	hypertrophic cardiomyopathy	Disease	D002312
15266362	276	297	biventricular failure	Disease	D018754
15266362	328	338	dobutamine	Chemical	D004280
15266362	462	490	left ventricular dysfunction	Disease	D018487
15266362	530	550	mitral regurgitation	Disease	D008944
15266362	604	631	hypertrophic cardiomyopathy	Disease	D002312
15266362	636	647	myocarditis	Disease	D009205
15266362	675	686	Myocarditis	Disease	D009205
15266362	699	723	eosinophilic myocarditis	Disease	D004802|D009205	eosinophilic|myocarditis
15266362	756	772	hypersensitivity	Disease	D004342
15266362	774	786	eosinophilic	Disease	D004802
15266362	788	799	myocarditis	Disease	D009205
15266362	815	825	dobutamine	Chemical	D004280
15266362	844	868	Eosinophilic myocarditis	Disease	D004802|D009205	Eosinophilic|myocarditis
15266362	CID	D004280	D004802
15266362	CID	D004280	D004342
15266362	CID	D004280	D009205

14648024|t|All- trans-retinoic acid-induced erythema nodosum in patients with acute promyelocytic leukemia.
14648024|a|Erythema nodosum associated with all- trans-retinoic acid (ATRA) for acute promyelocytic leukemia (APL) is very rare. We describe four patients with classic APL who developed erythema nodosum during ATRA therapy. Fever and subsequent multiple painful erythematous nodules over extremities developed on D11, D16, D17, and D19, respectively, after ATRA therapy. The skin biopsy taken from each patient was consistent with erythema nodosum. All patients received short course of steroids. Fever subsided rapidly and the skin lesions regressed completely. All patients achieved complete remission without withdrawal of ATRA. ATRA seemed to be the most possible etiology of erythema nodosum in our patients. Short-term use of steroid is very effective in ATRA-induced erythema nodosum.
14648024	0	24	All- trans-retinoic acid	Chemical	D014212
14648024	33	49	erythema nodosum	Disease	D004893
14648024	67	95	acute promyelocytic leukemia	Disease	D015473
14648024	97	113	Erythema nodosum	Disease	D004893
14648024	130	154	all- trans-retinoic acid	Chemical	D014212
14648024	156	160	ATRA	Chemical	D014212
14648024	166	194	acute promyelocytic leukemia	Disease	D015473
14648024	196	199	APL	Disease	D015473
14648024	254	257	APL	Disease	D015473
14648024	272	288	erythema nodosum	Disease	D004893
14648024	296	300	ATRA	Chemical	D014212
14648024	310	315	Fever	Disease	D005334
14648024	340	347	painful	Disease	D010146
14648024	348	368	erythematous nodules	Disease	D004893
14648024	443	447	ATRA	Chemical	D014212
14648024	517	533	erythema nodosum	Disease	D004893
14648024	573	581	steroids	Chemical	D013256
14648024	583	588	Fever	Disease	D005334
14648024	712	716	ATRA	Chemical	D014212
14648024	718	722	ATRA	Chemical	D014212
14648024	766	782	erythema nodosum	Disease	D004893
14648024	818	825	steroid	Chemical	D013256
14648024	847	851	ATRA	Chemical	D014212
14648024	860	876	erythema nodosum	Disease	D004893
14648024	CID	D014212	D004893
14648024	CID	D014212	D005334

11827497|t|Delayed-onset heparin-induced thrombocytopenia.
11827497|a|BACKGROUND: Heparin-induced thrombocytopenia presents 5 to 12 days after heparin exposure, with or without arterial or venous thromboemboli. Delayed recognition and treatment of heparin-induced thrombocytopenia contribute to poor patient outcomes. OBJECTIVE: To describe and increase awareness of a clinical scenario in which the onset or manifestations of heparin-induced thrombocytopenia are delayed. DESIGN: Retrospective case series. SETTING: Three large urban hospitals (with active cardiovascular surgery programs). PATIENTS: 14 patients seen over a 3-year period in whom heparin-induced thrombocytopenia became apparent on delayed presentation with thromboembolic complications. MEASUREMENTS: Platelet counts, onset of objectively determined thromboembolism, results of heparin-induced platelet factor 4 antibody tests, and outcomes. RESULTS: Patients went home after hospitalizations that had included heparin exposure--in most cases, with no thrombocytopenia recognized--only to return to the hospital (median, day 14) with thromboembolic complications. Thromboemboli were venous (12 patients, 7 with pulmonary emboli) or arterial (4 patients) or both. Platelet counts were mildly decreased in all but 2 patients on second presentation. On readmission, 11 patients received therapeutic heparin, which worsened the patients' clinical condition and, in all 11 cases, decreased the platelet count (mean at readmission, 143 x 10(9) cells/L; mean nadir after heparin re-exposure, 39 x 10(9) cells/L). Results of serologic tests for heparin-induced antibodies were positive in all patients. Subsequent treatments included alternative anticoagulants (11 patients), thrombolytic drugs (3 patients), inferior vena cava filters (3 patients) and, eventually, warfarin (11 patients). Three patients died. CONCLUSIONS: Delayed-onset heparin-induced thrombocytopenia is increasingly being recognized. To avoid disastrous outcomes, physicians must consider heparin-induced thrombocytopenia whenever a recently hospitalized patient returns with thromboembolism; therapy with alternative anticoagulants, not heparin, should be initiated.
11827497	14	21	heparin	Chemical	D006493
11827497	30	46	thrombocytopenia	Disease	D013921
11827497	60	67	Heparin	Chemical	D006493
11827497	76	92	thrombocytopenia	Disease	D013921
11827497	121	128	heparin	Chemical	D006493
11827497	155	187	arterial or venous thromboemboli	Disease	D001157|D054556	arterial thromboemboli|venous thromboemboli
11827497	226	233	heparin	Chemical	D006493
11827497	242	258	thrombocytopenia	Disease	D013921
11827497	405	412	heparin	Chemical	D006493
11827497	421	437	thrombocytopenia	Disease	D013921
11827497	626	633	heparin	Chemical	D006493
11827497	642	658	thrombocytopenia	Disease	D013921
11827497	704	718	thromboembolic	Disease	D013923
11827497	797	812	thromboembolism	Disease	D013923
11827497	825	832	heparin	Chemical	D006493
11827497	958	965	heparin	Chemical	D006493
11827497	999	1015	thrombocytopenia	Disease	D013921
11827497	1081	1095	thromboembolic	Disease	D013923
11827497	1111	1124	Thromboemboli	Disease	D013923
11827497	1158	1174	pulmonary emboli	Disease	D011655
11827497	1343	1350	heparin	Chemical	D006493
11827497	1511	1518	heparin	Chemical	D006493
11827497	1584	1591	heparin	Chemical	D006493
11827497	1805	1813	warfarin	Chemical	D014859
11827497	1877	1884	heparin	Chemical	D006493
11827497	1893	1909	thrombocytopenia	Disease	D013921
11827497	1999	2006	heparin	Chemical	D006493
11827497	2015	2031	thrombocytopenia	Disease	D013921
11827497	2086	2101	thromboembolism	Disease	D013923
11827497	2148	2155	heparin	Chemical	D006493
11827497	CID	D006493	D054556
11827497	CID	D006493	D013921
11827497	CID	D006493	D001157
11827497	CID	D006493	D011655

8841157|t|Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: a comparative study of the efficacy and safety against amlodipine.
8841157|a|OBJECTIVE: To compare the antihypertensive efficacy of a new angiotensin II antagonist, valsartan, with a reference therapy, amlodipine. METHODS: One hundred sixty-eight adult outpatients with mild to moderate hypertension were randomly allocated in double-blind fashion and equal number to receive 80 mg valsartan or 5 mg amlodipine for 12 weeks. After 8 weeks of therapy, in patients whose blood pressure remained uncontrolled, 5 mg amlodipine was added to the initial therapy. Patients were assessed at 4, 8, and 12 weeks. The primary efficacy variable was change from baseline in mean sitting diastolic blood pressure at 8 weeks. Secondary variables included change in sitting systolic blood pressure and responder rates. RESULTS: Both valsartan and amlodipine were effective at lowering blood pressure at 4, 8, and 12 weeks. Similar decreases were observed in both groups, with no statistically significant differences between the groups for any variable analyzed. For the primary variable the difference was 0.5 mm Hg in favor of valsartan (p = 0.68; 95% confidence interval, -2.7 to 1.7). Responder rates at 8 weeks were 66.7% for valsartan and 60.2% for amlodipine (p = 0.39). Both treatments were well tolerated. The incidence of drug-related dependent edema was somewhat higher in the amlodipine group, particularly at a dose of 10 mg per day (2.4% for 80 mg valsartan; 3.6% for 5 mg amlodipine; 0% for valsartan plus 5 mg amlodipine; 14.3% for 10 mg amlodipine). CONCLUSIONS: The data show that valsartan is at least as effective as amlodipine in the treatment of mild to moderate hypertension. The results also show valsartan to be well tolerated and suggest that it is not associated with side effects characteristic of this comparator class, dihydropyridine calcium antagonists.
8841157	0	9	Valsartan	Chemical	C081489
8841157	17	31	angiotensin II	Chemical	D000804
8841157	74	86	hypertension	Disease	D006973
8841157	143	153	amlodipine	Chemical	D017311
8841157	216	230	angiotensin II	Chemical	D000804
8841157	243	252	valsartan	Chemical	C081489
8841157	280	290	amlodipine	Chemical	D017311
8841157	365	377	hypertension	Disease	D006973
8841157	460	469	valsartan	Chemical	C081489
8841157	478	488	amlodipine	Chemical	D017311
8841157	590	600	amlodipine	Chemical	D017311
8841157	895	904	valsartan	Chemical	C081489
8841157	909	919	amlodipine	Chemical	D017311
8841157	1191	1200	valsartan	Chemical	C081489
8841157	1293	1302	valsartan	Chemical	C081489
8841157	1317	1327	amlodipine	Chemical	D017311
8841157	1417	1422	edema	Disease	D004487
8841157	1450	1460	amlodipine	Chemical	D017311
8841157	1524	1533	valsartan	Chemical	C081489
8841157	1549	1559	amlodipine	Chemical	D017311
8841157	1568	1577	valsartan	Chemical	C081489
8841157	1588	1598	amlodipine	Chemical	D017311
8841157	1616	1626	amlodipine	Chemical	D017311
8841157	1661	1670	valsartan	Chemical	C081489
8841157	1699	1709	amlodipine	Chemical	D017311
8841157	1747	1759	hypertension	Disease	D006973
8841157	1783	1792	valsartan	Chemical	C081489
8841157	1911	1926	dihydropyridine	Chemical	C038806
8841157	1927	1934	calcium	Chemical	D002118
8841157	CID	C081489	D004487
8841157	CID	D017311	D004487

8045270|t|KF17837: a novel selective adenosine A2A receptor antagonist with anticataleptic activity.
8045270|a|KF17837 is a novel selective adenosine A2A receptor antagonist. Oral administration of KF17837 (2.5, 10.0 and 30.0 mg/kg) significantly ameliorated the cataleptic responses induced by intracerebroventricular administration of an adenosine A2A receptor agonist, CGS 21680 (10 micrograms), in a dose-dependent manner. KF17837 also reduced the catalepsy induced by haloperidol (1 mg/kg i.p.) and by reserpine (5 mg/kg i.p.). These anticataleptic effects were exhibited dose dependently at doses from 0.625 and 2.5 mg/kg p.o., respectively. Moreover, KF17837 (0.625 mg/kg p.o.) potentiated the anticataleptic effects of a subthreshold dose of L-3,4-dihydroxyphenylalanine (L-DOPA; 25 mg/kg i.p.) plus benserazide (6.25 mg/kg i.p.). These results suggested that KF17837 is a centrally active adenosine A2A receptor antagonist and that the dopaminergic function of the nigrostriatal pathway is potentiated by adenosine A2A receptor antagonists. Furthermore, KF17837 may be a useful drug in the treatment of parkinsonism.
8045270	0	7	KF17837	Chemical	C081198
8045270	27	36	adenosine	Chemical	D000241
8045270	91	98	KF17837	Chemical	C081198
8045270	120	129	adenosine	Chemical	D000241
8045270	178	185	KF17837	Chemical	C081198
8045270	243	253	cataleptic	Disease	D002375
8045270	320	329	adenosine	Chemical	D000241
8045270	352	361	CGS 21680	Chemical	C061282
8045270	407	414	KF17837	Chemical	C081198
8045270	432	441	catalepsy	Disease	D002375
8045270	453	464	haloperidol	Chemical	D006220
8045270	487	496	reserpine	Chemical	D012110
8045270	638	645	KF17837	Chemical	C081198
8045270	730	758	L-3,4-dihydroxyphenylalanine	Chemical	D007980
8045270	760	766	L-DOPA	Chemical	D007980
8045270	788	799	benserazide	Chemical	D001545
8045270	848	855	KF17837	Chemical	C081198
8045270	878	887	adenosine	Chemical	D000241
8045270	994	1003	adenosine	Chemical	D000241
8045270	1043	1050	KF17837	Chemical	C081198
8045270	1092	1104	parkinsonism	Disease	D010302
8045270	CID	D012110	D002375
8045270	CID	C061282	D002375
8045270	CID	D006220	D002375

2576810|t|Some central effects of repeated treatment with fluvoxamine.
2576810|a|We investigated the effect of repeated treatment with fluvoxamine, a selective serotonin uptake inhibitor, on behavioral effects of dopaminomimetics and methoxamine and on the animal behavior in the "behavioral despair" test. A repeated treatment with fluvoxamine (twice daily for 14 days) potentiated in mice and in rats (weaker) the amphetamine-induced hyperactivity. The hyperactivity induced by nomifensine in mice remained unaffected by fluvoxamine. The stimulation of locomotor activity by intracerebroventricularly administered methoxamine was not affected by repeated treatment with fluvoxamine. Given three times fluvoxamine had no effect on the immobilization time in the "behavioral despair" test in rats. The results indicate that fluvoxamine given repeatedly acts differently than citalopram, another selective serotonin uptake inhibitor, and differs also from other antidepressant drugs.
2576810	48	59	fluvoxamine	Chemical	D016666
2576810	115	126	fluvoxamine	Chemical	D016666
2576810	140	149	serotonin	Chemical	D012701
2576810	214	225	methoxamine	Chemical	D008729
2576810	313	324	fluvoxamine	Chemical	D016666
2576810	396	407	amphetamine	Chemical	D000661
2576810	416	429	hyperactivity	Disease	D006948
2576810	435	448	hyperactivity	Disease	D006948
2576810	460	471	nomifensine	Chemical	D009627
2576810	503	514	fluvoxamine	Chemical	D016666
2576810	596	607	methoxamine	Chemical	D008729
2576810	652	663	fluvoxamine	Chemical	D016666
2576810	683	694	fluvoxamine	Chemical	D016666
2576810	804	815	fluvoxamine	Chemical	D016666
2576810	855	865	citalopram	Chemical	D015283
2576810	885	894	serotonin	Chemical	D012701
2576810	CID	D016666	D006948
2576810	CID	D008729	D006948
2576810	CID	D009627	D006948
2576810	CID	D000661	D006948

20635749|t|Severe congestive heart failure patient on amiodarone presenting with myxedemic coma: a case report.
20635749|a|This is a case report of myxedema coma secondary to amiodarone-induced hypothyroidism in a patient with severe congestive heart failure (CHF). To our knowledge and after reviewing the literature there is one case report of myxedema coma during long term amiodarone therapy. Myxedema coma is a life threatening condition that carries a mortality reaching as high as 20% with treatment. The condition is treated with intravenous thyroxine (T4) or intravenous tri-iodo-thyronine (T3). Patients with CHF on amiodarone may suffer serious morbidity and mortality from hypothyroidism, and thus may deserve closer follow up for thyroid stimulating hormone (TSH) levels. This case report carries an important clinical application given the frequent usage of amiodarone among CHF patients. The myriad clinical presentation of myxedema coma and its serious morbidity and mortality stresses the need to suspect this clinical syndrome among CHF patients presenting with hypotension, weakness or other unexplained symptoms.
20635749	7	31	congestive heart failure	Disease	D006333
20635749	43	53	amiodarone	Chemical	D000638
20635749	70	84	myxedemic coma	Disease	D009230|D003128	myxedemic|coma
20635749	126	139	myxedema coma	Disease	D009230|D003128	myxedema|coma
20635749	153	163	amiodarone	Chemical	D000638
20635749	172	186	hypothyroidism	Disease	D007037
20635749	212	236	congestive heart failure	Disease	D006333
20635749	238	241	CHF	Disease	D006333
20635749	324	337	myxedema coma	Disease	D009230|D003128	myxedema|coma
20635749	355	365	amiodarone	Chemical	D000638
20635749	375	388	Myxedema coma	Disease	D009230|D003128	Myxedema|coma
20635749	528	537	thyroxine	Chemical	D013974
20635749	539	541	T4	Chemical	D013974
20635749	558	576	tri-iodo-thyronine	Chemical	D014284
20635749	578	580	T3	Chemical	D014284
20635749	597	600	CHF	Disease	D006333
20635749	604	614	amiodarone	Chemical	D000638
20635749	663	677	hypothyroidism	Disease	D007037
20635749	850	860	amiodarone	Chemical	D000638
20635749	867	870	CHF	Disease	D006333
20635749	917	930	myxedema coma	Disease	D009230|D003128	myxedema|coma
20635749	1029	1032	CHF	Disease	D006333
20635749	1058	1069	hypotension	Disease	D007022
20635749	1071	1079	weakness	Disease	D018908
20635749	CID	D000638	D003128
20635749	CID	D000638	D009230
20635749	CID	D000638	D007037

20394767|t|Fear-potentiated startle, but not light-enhanced startle, is enhanced by anxiogenic drugs.
20394767|a|RATIONALE AND OBJECTIVES: The light-enhanced startle paradigm (LES) is suggested to model anxiety, because of the non-specific cue and the long-term effect. In contrast, the fear-potentiated startle (FPS) is suggested to model conditioned fear. However, the pharmacological profiles of these two paradigms are very similar. The present study investigated the effects of putative anxiogenic drugs on LES and FPS and aimed at determining the sensitivity of LES for anxiogenic drugs and to potentially showing a pharmacological differentiation between these two paradigms. METHODS: Male Wistar rats received each dose of the alpha(2)-adrenoceptor antagonist yohimbine (0.25-1.0mg/kg), the 5-HT(2C) receptor agonist m-chlorophenylpiperazine (mCPP, 0.5-2.0mg/kg) or the GABA(A) inverse receptor agonist pentylenetetrazole (PTZ, 3-30mg/kg) and were subsequently tested in either LES or FPS. RESULTS: None of the drugs enhanced LES, whereas mCPP increased percentage FPS and yohimbine increased absolute FPS values. Furthermore, yohimbine increased baseline startle amplitude in the LES, while mCPP suppressed baseline startle in both the LES and FPS and PTZ suppressed baseline startle in the FPS. CONCLUSIONS: In contrast to findings in the FPS paradigm, none of the drugs were able to exacerbate the LES response. Thus, a clear pharmacological differentiation was found between LES and FPS.
20394767	17	24	startle	Disease	D012021
20394767	49	56	startle	Disease	D012021
20394767	136	143	startle	Disease	D012021
20394767	181	188	anxiety	Disease	D001008
20394767	282	289	startle	Disease	D012021
20394767	746	755	yohimbine	Chemical	D015016
20394767	777	781	5-HT	Chemical	D012701
20394767	803	827	m-chlorophenylpiperazine	Chemical	C015068
20394767	829	833	mCPP	Chemical	C015068
20394767	856	860	GABA	Chemical	D005680
20394767	889	907	pentylenetetrazole	Chemical	D010433
20394767	909	912	PTZ	Chemical	D010433
20394767	1025	1029	mCPP	Chemical	C015068
20394767	1059	1068	yohimbine	Chemical	D015016
20394767	1113	1122	yohimbine	Chemical	D015016
20394767	1142	1149	startle	Disease	D012021
20394767	1178	1182	mCPP	Chemical	C015068
20394767	1203	1210	startle	Disease	D012021
20394767	1239	1242	PTZ	Chemical	D010433
20394767	1263	1270	startle	Disease	D012021
20394767	CID	D010433	D012021
20394767	CID	D015016	D012021
20394767	CID	C015068	D012021

19203554|t|Proteinase 3-antineutrophil cytoplasmic antibody-(PR3-ANCA) positive necrotizing glomerulonephritis after restarting sulphasalazine treatment.
19203554|a|A 59-year-old woman with ulcerative colitis developed red eyes, pleural effusion, eosinophilia and urinary abnormalities after restarting of sulphasalazine treatment. Light microscopy of a kidney biopsy revealed segmental necrotizing glomerulonephritis without deposition of immunoglobulin or complement. Proteinase 3-antineutrophil cytoplasmic antibody (PR3-ANCA) titer was elevated at 183 ELISA units (EU) in sera (normal range less than 10 EU), myeloperoxidase-ANCA was negative. PR3-ANCA titer was 250 and 1,070 EU in pleural effusions on right and left side, respectively. Although cessation of sulphasalazine treatment resulted in improvements in fever, red eyes, chest pain, titer of C-reactive protein and volume of the pleural effusions, we initiated steroid therapy, because PR3-ANCA titer rose to 320 EU, eosinophil count increased to 1,100 cells/microl, and the pleural effusion remained. One month after steroid therapy, the pleural effusion disappeared, and PR3-ANCA titer normalized 3 months later. This case suggests that sulphasalazine can induce PR3-ANCA-positive necrotizing glomerulonephritis.
19203554	81	99	glomerulonephritis	Disease	D005921
19203554	117	131	sulphasalazine	Chemical	D012460
19203554	168	186	ulcerative colitis	Disease	D003093
19203554	197	205	red eyes	Disease	D005128
19203554	207	223	pleural effusion	Disease	D010996
19203554	225	237	eosinophilia	Disease	D004802
19203554	242	263	urinary abnormalities	Disease	D001745
19203554	284	298	sulphasalazine	Chemical	D012460
19203554	355	395	segmental necrotizing glomerulonephritis	Disease	D005923
19203554	665	682	pleural effusions	Disease	D010996
19203554	743	757	sulphasalazine	Chemical	D012460
19203554	796	801	fever	Disease	D005334
19203554	803	811	red eyes	Disease	D005128
19203554	813	823	chest pain	Disease	D002637
19203554	871	888	pleural effusions	Disease	D010996
19203554	903	910	steroid	Chemical	D013256
19203554	1017	1033	pleural effusion	Disease	D010996
19203554	1060	1067	steroid	Chemical	D013256
19203554	1081	1097	pleural effusion	Disease	D010996
19203554	1181	1195	sulphasalazine	Chemical	D012460
19203554	1237	1255	glomerulonephritis	Disease	D005921
19203554	CID	D012460	D005334
19203554	CID	D012460	D005923
19203554	CID	D012460	D010996

17049862|t|Is phenytoin administration safe in a hypothermic child?
17049862|a|A male neonate with a Chiari malformation and a leaking myelomeningocoele underwent ventriculoperitoneal shunt insertion followed by repair of myelomeningocoele. During anaesthesia and surgery, he inadvertently became moderately hypothermic. Intravenous phenytoin was administered during the later part of the surgery for seizure prophylaxis. Following phenytoin administration, the patient developed acute severe bradycardia, refractory to atropine and adrenaline. The cardiac depressant actions of phenytoin and hypothermia can be additive. Administration of phenytoin in the presence of hypothermia may lead to an adverse cardiac event in children. As phenytoin is a commonly used drug, clinicians need to be aware of this interaction.
17049862	3	12	phenytoin	Chemical	D010672
17049862	38	49	hypothermic	Disease	D007035
17049862	79	98	Chiari malformation	Disease	D001139
17049862	286	297	hypothermic	Disease	D007035
17049862	311	320	phenytoin	Chemical	D010672
17049862	379	386	seizure	Disease	D012640
17049862	410	419	phenytoin	Chemical	D010672
17049862	471	482	bradycardia	Disease	D001919
17049862	498	506	atropine	Chemical	D001285
17049862	511	521	adrenaline	Chemical	D004837
17049862	557	566	phenytoin	Chemical	D010672
17049862	571	582	hypothermia	Disease	D007035
17049862	618	627	phenytoin	Chemical	D010672
17049862	647	658	hypothermia	Disease	D007035
17049862	712	721	phenytoin	Chemical	D010672
17049862	CID	D010672	D001919

16225977|t|Amisulpride related tic-like symptoms in an adolescent schizophrenic.
16225977|a|Tic disorders can be effectively treated by atypical antipsychotics such as risperidone, olanzapine and ziprasidone. However, there are two case reports that show tic-like symptoms, including motor and phonic variants, occurring during treatment with quetiapine or clozapine. We present a 15-year-old girl schizophrenic who developed frequent involuntary eye-blinking movements after 5 months of amisulpride treatment (1000 mg per day). The tic-like symptoms resolved completely after we reduced the dose of amisulpride down to 800 mg per day. However, her psychosis recurred after the dose reduction. We then placed her on an additional 100 mg per day of quetiapine. She has been in complete remission under the combined medications for more than one year and maintains a fair role function. No more tic-like symptoms or other side effects have been reported. Together with previously reported cases, our patient suggests that tic-like symptoms might occur in certain vulnerable individuals during treatment with atypical antipsychotics such as quetiapine, clozapine, or amisulpride.
16225977	0	11	Amisulpride	Chemical	C012052
16225977	20	37	tic-like symptoms	Disease	D013981
16225977	55	68	schizophrenic	Disease	D012559
16225977	70	83	Tic disorders	Disease	D013981
16225977	146	157	risperidone	Chemical	D018967
16225977	159	169	olanzapine	Chemical	C076029
16225977	174	185	ziprasidone	Chemical	C092292
16225977	233	250	tic-like symptoms	Disease	D013981
16225977	321	331	quetiapine	Chemical	C069541
16225977	335	344	clozapine	Chemical	D003024
16225977	376	389	schizophrenic	Disease	D012559
16225977	413	447	involuntary eye-blinking movements	Disease	D020820
16225977	466	477	amisulpride	Chemical	C012052
16225977	511	528	tic-like symptoms	Disease	D013981
16225977	578	589	amisulpride	Chemical	C012052
16225977	627	636	psychosis	Disease	D011605
16225977	726	736	quetiapine	Chemical	C069541
16225977	871	888	tic-like symptoms	Disease	D013981
16225977	998	1015	tic-like symptoms	Disease	D013981
16225977	1116	1126	quetiapine	Chemical	C069541
16225977	1128	1137	clozapine	Chemical	D003024
16225977	1142	1153	amisulpride	Chemical	C012052
16225977	CID	C012052	D013981

12852481|t|Comparison of developmental toxicology of aspirin (acetylsalicylic acid) in rats using selected dosing paradigms.
12852481|a|BACKGROUND: Analysis of the literature for nonsteroidal anti-inflammatory drugs (NSAIDs) suggests that a low incidence of developmental anomalies occurs in rats given NSAIDs on specific days during organogenesis. Aspirin (acetylsalicylic acid [ASA]), an irreversible cyclooxygenase 1 and 2 inhibitor, induces developmental anomalies when administered to Wistar rats on gestational day (GD) 9, 10, or 11 (Kimmel CA, Wilson JG, Schumacher HJ. Teratology 4:15-24, 1971). There are no published ASA studies using the multiple dosing paradigm of GDs 6 to 17. Objectives of the current study were to compare results between Sprague-Dawley (SD) and Wistar strains when ASA is administered on GD 9, 10, or 11; to compare the malformation patterns following single and multiple dosings during organogenesis in SD rats; and to test the hypothesis that maternal gastrointestinal toxicity confounds the detection of low incidence malformations with ASA when a multiple dosing paradigm is used. METHODS: ASA was administered as a single dose on GD 9 (0, 250, 500, or 625 mg/kg), 10 (0, 500, 625, or 750 mg/kg), or 11 (0, 500, 750, or 1000 mg/kg) and from GD 6 to GD 17 (0, 50, 125, or 250 mg/kg a day) in the multiple dose study to SD rats. Animals were killed on GD 21, and fetuses were examined viscerally. RESULTS: The literature evaluation suggested that NSAIDs induce ventricular septal defects (VSDs) and midline defects (MDs) in rats and diaphragmatic hernia (DH), MDs, and VSDs in rabbits (Cook JC et al., 2003); hence, the present study focused on these malformations, even though ASA induces several other low-incidence malformations. In single dose studies, DH, MD, and VSD were induced on GDs 9 and 10. VSD also was noted following treatment on GD 11. In contrast, DH and MD were noted in the multiple dose study design only in the high-dose group, and VSD was noted across all dose groups. CONCLUSIONS: High concordance in major developmental anomalies between Wistar and SD rats were noted with the exception of VSD in the SD rats and hydrocephalus in the Wistar rats. Variations and malformations were similar when ASA was administered as a single dose or during the period of organogenesis (GDs 6 to 17). It was also evident that, by titrating the dose to achieve a maximum tolerated dose, malformations that normally occur at low incidence, as reported from previous single dose studies, could also be induced with ASA given at multiple doses.
12852481	42	49	aspirin	Chemical	D001241
12852481	51	71	acetylsalicylic acid	Chemical	D001241
12852481	236	259	developmental anomalies	Disease	D000014
12852481	327	334	Aspirin	Chemical	D001241
12852481	336	356	acetylsalicylic acid	Chemical	D001241
12852481	358	361	ASA	Chemical	D001241
12852481	423	446	developmental anomalies	Disease	D000014
12852481	605	608	ASA	Chemical	D001241
12852481	776	779	ASA	Chemical	D001241
12852481	965	990	gastrointestinal toxicity	Disease	D005767
12852481	1032	1045	malformations	Disease	D000014
12852481	1051	1054	ASA	Chemical	D001241
12852481	1105	1108	ASA	Chemical	D001241
12852481	1474	1500	ventricular septal defects	Disease	D006345
12852481	1502	1506	VSDs	Disease	D006345
12852481	1512	1527	midline defects	Disease	D009436
12852481	1529	1532	MDs	Disease	D009436
12852481	1546	1566	diaphragmatic hernia	Disease	D065630
12852481	1568	1570	DH	Disease	D065630
12852481	1573	1576	MDs	Disease	D009436
12852481	1582	1586	VSDs	Disease	D006345
12852481	1664	1677	malformations	Disease	D000014
12852481	1691	1694	ASA	Chemical	D001241
12852481	1731	1744	malformations	Disease	D000014
12852481	1770	1772	DH	Disease	D065630
12852481	1774	1776	MD	Disease	D009436
12852481	1782	1785	VSD	Disease	D006345
12852481	1816	1819	VSD	Disease	D006345
12852481	1878	1880	DH	Disease	D065630
12852481	1885	1887	MD	Disease	D009436
12852481	1966	1969	VSD	Disease	D006345
12852481	2043	2066	developmental anomalies	Disease	D000014
12852481	2127	2130	VSD	Disease	D006345
12852481	2150	2163	hydrocephalus	Disease	D006849
12852481	2199	2212	malformations	Disease	D000014
12852481	2231	2234	ASA	Chemical	D001241
12852481	2407	2420	malformations	Disease	D000014
12852481	2533	2536	ASA	Chemical	D001241
12852481	CID	D001241	D065630
12852481	CID	D001241	D000014
12852481	CID	D001241	D006345

11858397|t|Torsade de pointes induced by metoclopramide in an elderly woman with preexisting complete left bundle branch block.
11858397|a|There is a growing list of drugs implicated in acquired long QT syndrome and torsade de pointes. However, the torsadogenic potential of metoclopramide, a commonly used antiemetic and prokinetic drug, has not been reported in the literature, despite its chemical similarity to procainamide. We report on a 92-year-old woman with preexisting complete left bundle branch block who developed torsade de pointes after intravenous and oral administration of metoclopramide. This patient also developed torsade de pointes when cisapride and erythromycin were given simultaneously. These two episodes were suppressed successfully after discontinuing the offending drugs and administering class IB drugs. This is the first documentation that metoclopramide provokes torsade de pointes clinically. Metoclopramide should be used cautiously in patients with a risk of torsade de pointes.
11858397	0	18	Torsade de pointes	Disease	D016171
11858397	30	44	metoclopramide	Chemical	D008787
11858397	91	115	left bundle branch block	Disease	D002037
11858397	173	189	long QT syndrome	Disease	D008133
11858397	194	212	torsade de pointes	Disease	D016171
11858397	253	267	metoclopramide	Chemical	D008787
11858397	393	405	procainamide	Chemical	D011342
11858397	466	490	left bundle branch block	Disease	D002037
11858397	505	523	torsade de pointes	Disease	D016171
11858397	569	583	metoclopramide	Chemical	D008787
11858397	613	631	torsade de pointes	Disease	D016171
11858397	637	646	cisapride	Chemical	D020117
11858397	651	663	erythromycin	Chemical	D004917
11858397	850	864	metoclopramide	Chemical	D008787
11858397	874	892	torsade de pointes	Disease	D016171
11858397	905	919	Metoclopramide	Chemical	D008787
11858397	973	991	torsade de pointes	Disease	D016171
11858397	CID	D008787	D016171
11858397	CID	D004917	D016171
11858397	CID	D020117	D016171

11009181|t|Apomorphine: an underutilized therapy for Parkinson's disease.
11009181|a|Apomorphine was the first dopaminergic drug ever used to treat symptoms of Parkinson's disease. While powerful antiparkinsonian effects had been observed as early as 1951, the potential of treating fluctuating Parkinson's disease by subcutaneous administration of apomorphine has only recently become the subject of systematic study. A number of small scale clinical trials have unequivocally shown that intermittent subcutaneous apomorphine injections produce antiparkinsonian benefit close if not identical to that seen with levodopa and that apomorphine rescue injections can reliably revert off-periods even in patients with complex on-off motor swings. Continuous subcutaneous apomorphine infusions can reduce daily off-time by more than 50% in this group of patients, which appears to be a stronger effect than that generally seen with add-on therapy with oral dopamine agonists or COMT inhibitors. Extended follow-up studies of up to 8 years have demonstrated long-term persistence of apomorphine efficacy. In addition, there is convincing clinical evidence that monotherapy with continuous subcutaneous apomorphine infusions is associated with marked reductions of preexisting levodopa-induced dyskinesias. The main side effects of subcutaneous apomorphine treatment are related to cutaneous tolerability problems, whereas sedation and psychiatric complications play a lesser role. Given the marked degree of efficacy of subcutaneous apomorphine treatment in fluctuating Parkinson's disease, this approach seems to deserve more widespread clinical use.
11009181	0	11	Apomorphine	Chemical	D001058
11009181	42	61	Parkinson's disease	Disease	D010300
11009181	63	74	Apomorphine	Chemical	D001058
11009181	138	157	Parkinson's disease	Disease	D010300
11009181	273	292	Parkinson's disease	Disease	D010300
11009181	327	338	apomorphine	Chemical	D001058
11009181	493	504	apomorphine	Chemical	D001058
11009181	590	598	levodopa	Chemical	D007980
11009181	608	619	apomorphine	Chemical	D001058
11009181	745	756	apomorphine	Chemical	D001058
11009181	930	938	dopamine	Chemical	D004298
11009181	1055	1066	apomorphine	Chemical	D001058
11009181	1174	1185	apomorphine	Chemical	D001058
11009181	1248	1256	levodopa	Chemical	D007980
11009181	1265	1276	dyskinesias	Disease	D004409
11009181	1316	1327	apomorphine	Chemical	D001058
11009181	1407	1418	psychiatric	Disease	D001523
11009181	1505	1516	apomorphine	Chemical	D001058
11009181	1542	1561	Parkinson's disease	Disease	D010300
11009181	CID	D007980	D004409

8988571|t|Fatal excited delirium following cocaine use: epidemiologic findings provide new evidence for mechanisms of cocaine toxicity.
8988571|a|We describe an outbreak of deaths from cocaine-induced excited delirium (EDDs) in Dade County, Florida between 1979 and 1990. From a registry of all cocaine-related deaths in Dade County, Florida, from 1969-1990, 58 EDDs were compared with 125 victims of accidental cocaine overdose without excited delirium. Compared with controls, EDDs were more frequently black, male, and younger. They were less likely to have a low body mass index, and more likely to have died in police custody, to have received medical treatment immediately before death, to have survived for a longer period, to have developed hyperthermia, and to have died in summer months. EDDs had concentrations of cocaine and benzoylecgonine in autopsy blood that were similar to those for controls. The epidemiologic findings are most consistent with the hypothesis that chronic cocaine use disrupts dopaminergic function and, when coupled with recent cocaine use, may precipitate agitation, delirium, aberrant thermoregulation, rhabdomyolysis, and sudden death.
8988571	14	22	delirium	Disease	D003693
8988571	33	40	cocaine	Chemical	D003042
8988571	108	115	cocaine	Chemical	D003042
8988571	116	124	toxicity	Disease	D064420
8988571	165	172	cocaine	Chemical	D003042
8988571	189	197	delirium	Disease	D003693
8988571	199	203	EDDs	Disease	D003693
8988571	275	282	cocaine	Chemical	D003042
8988571	342	346	EDDs	Disease	D003693
8988571	392	399	cocaine	Chemical	D003042
8988571	400	408	overdose	Disease	D062787
8988571	425	433	delirium	Disease	D003693
8988571	459	463	EDDs	Disease	D003693
8988571	729	741	hyperthermia	Disease	D005334
8988571	778	782	EDDs	Disease	D003693
8988571	805	812	cocaine	Chemical	D003042
8988571	817	832	benzoylecgonine	Chemical	C005618
8988571	971	978	cocaine	Chemical	D003042
8988571	1044	1051	cocaine	Chemical	D003042
8988571	1073	1082	agitation	Disease	D011595
8988571	1084	1092	delirium	Disease	D003693
8988571	1121	1135	rhabdomyolysis	Disease	D012206
8988571	1141	1153	sudden death	Disease	D003645
8988571	CID	D003042	D012206
8988571	CID	D003042	D003645
8988571	CID	D003042	D003693

6615052|t|Heparin-induced thrombocytopenia, thrombosis, and hemorrhage.
6615052|a|Sixty-two patients with a heparin-induced thrombocytopenia are reported. Clinical manifestations of this disorder include hemorrhage or, more frequently, thromboembolic events in patients receiving heparin. Laboratory testing has revealed a falling platelet count, increased resistance to heparin, and aggregation of platelets by the patient's plasma when heparin is added. Immunologic testing has demonstrated the presence of a heparin-dependent platelet membrane antibody. The 20 deaths, 52 hemorrhagic and thromboembolic complications, and 21 surgical procedures to manage the complications confirm the seriousness of the disorder. Specific risk factors have not been identified; therefore, all patients receiving heparin should be monitored. If the platelet count falls to less than 100,000/mm3, while the patient is receiving heparin, platelet aggregation testing, using the patient's plasma, is indicated. Management consists of cessation of heparin, platelet anti-aggregating agents, and alternate forms of anticoagulation when indicated.
6615052	0	7	Heparin	Chemical	D006493
6615052	16	32	thrombocytopenia	Disease	D013921
6615052	34	44	thrombosis	Disease	D013927
6615052	50	60	hemorrhage	Disease	D006470
6615052	88	95	heparin	Chemical	D006493
6615052	104	120	thrombocytopenia	Disease	D013921
6615052	184	194	hemorrhage	Disease	D006470
6615052	216	230	thromboembolic	Disease	D013923
6615052	260	267	heparin	Chemical	D006493
6615052	301	325	a falling platelet count	Disease	D001791
6615052	351	358	heparin	Chemical	D006493
6615052	418	425	heparin	Chemical	D006493
6615052	491	498	heparin	Chemical	D006493
6615052	555	599	hemorrhagic and thromboembolic complications	Disease	D006470|D013923	hemorrhagic complications|thromboembolic complications
6615052	779	786	heparin	Chemical	D006493
6615052	893	900	heparin	Chemical	D006493
6615052	902	922	platelet aggregation	Disease	D001791
6615052	1010	1017	heparin	Chemical	D006493
6615052	CID	D006493	D013923
6615052	CID	D006493	D013921
6615052	CID	D006493	D006470

3952818|t|Cardiac toxicity of 5-fluorouracil. Report of a case of spontaneous angina.
3952818|a|We report a case of a patient with colon carcinoma and liver metastasis who presented chest pain after 5-fluorouracil (5-FU) administration. Clinical electrocardiographic evolution was similar to that observed in Prinzmetal's angina, and chest pain promptly resolved with nifedipine. These data suggest that coronary spasm may be the cause of cardiotoxicity due to 5-FU, and that calcium antagonists may probably be used in the prevention or treatment of 5-FU cardiotoxicity.
3952818	0	16	Cardiac toxicity	Disease	D066126
3952818	20	34	5-fluorouracil	Chemical	D005472
3952818	68	74	angina	Disease	D000787
3952818	111	126	colon carcinoma	Disease	D003110
3952818	137	147	metastasis	Disease	D009362
3952818	162	172	chest pain	Disease	D002637
3952818	179	193	5-fluorouracil	Chemical	D005472
3952818	195	199	5-FU	Chemical	D005472
3952818	289	308	Prinzmetal's angina	Disease	D000788
3952818	314	324	chest pain	Disease	D002637
3952818	348	358	nifedipine	Chemical	D009543
3952818	384	398	coronary spasm	Disease	D003329
3952818	419	433	cardiotoxicity	Disease	D066126
3952818	441	445	5-FU	Chemical	D005472
3952818	456	463	calcium	Chemical	D002118
3952818	531	535	5-FU	Chemical	D005472
3952818	536	550	cardiotoxicity	Disease	D066126
3952818	CID	D005472	D002637
3952818	CID	D005472	D000788

3084782|t|Toxicity due to remission inducing drugs in rheumatoid arthritis. Association with HLA-B35 and Cw4 antigens.
3084782|a|Twenty-five patients with rheumatoid arthritis (RA) who developed toxicity while taking remission inducing drugs and 30 without toxicity were studied for possible associations with class I and II HLA antigens. A strong association has been found between nephritis and dermatitis due to Tiopronin (a D-Penicillamine like compound) and class I antigens B35-Cw4, and between dermatitis due to gold thiosulphate and B35. Compared to healthy controls a lower DR5 frequency was observed in patients with RA except for the Tiopronin related nephritis group.
3084782	0	8	Toxicity	Disease	D064420
3084782	44	64	rheumatoid arthritis	Disease	D001172
3084782	135	155	rheumatoid arthritis	Disease	D001172
3084782	157	159	RA	Disease	D001172
3084782	175	183	toxicity	Disease	D064420
3084782	237	245	toxicity	Disease	D064420
3084782	363	372	nephritis	Disease	D009393
3084782	377	387	dermatitis	Disease	D003872
3084782	395	404	Tiopronin	Chemical	D008625
3084782	408	423	D-Penicillamine	Chemical	D010396
3084782	481	491	dermatitis	Disease	D003872
3084782	499	503	gold	Chemical	D006046
3084782	504	516	thiosulphate	Chemical	-1
3084782	607	609	RA	Disease	D001172
3084782	625	634	Tiopronin	Chemical	D008625
3084782	643	652	nephritis	Disease	D009393
3084782	CID	D006046	D003872
3084782	CID	D008625	D009393
3084782	CID	D008625	D003872

430165|t|Transient hemiparesis: a rare manifestation of diphenylhydantoin toxicity. Report of two cases.
430165|a|Among the common side effects of diphenylhydantoin (DPH) overdose, the most frequently encountered neurological signs are those of cerebellar dysfunction. Very rarely, the toxic neurological manifestations of this drug are of cerebral origin. Two patients are presented who suffered progressive hemiparesis due to DPH overdose. Both had brain surgery before DPH treatment. It is assumed that patients with some cerebral damage are liable to manifest DPH toxicity as focal neurological signs.
430165	10	21	hemiparesis	Disease	D010291
430165	47	64	diphenylhydantoin	Chemical	D010672
430165	65	73	toxicity	Disease	D064420
430165	129	146	diphenylhydantoin	Chemical	D010672
430165	148	151	DPH	Chemical	D010672
430165	153	161	overdose	Disease	D062787
430165	227	249	cerebellar dysfunction	Disease	D002526
430165	391	402	hemiparesis	Disease	D010291
430165	410	413	DPH	Chemical	D010672
430165	414	422	overdose	Disease	D062787
430165	454	457	DPH	Chemical	D010672
430165	507	522	cerebral damage	Disease	D001927
430165	546	549	DPH	Chemical	D010672
430165	550	558	toxicity	Disease	D064420
430165	CID	D010672	D062787
430165	CID	D010672	D002526
430165	CID	D010672	D010291

16600756|t|Nerve growth factor and prostaglandins in the urine of female patients with overactive bladder.
16600756|a|PURPOSE: NGF and PGs in the bladder can be affected by pathological changes in the bladder and these changes can be detected in urine. We investigated changes in urinary NGF and PGs in women with OAB. MATERIALS AND METHODS: The study groups included 65 women with OAB and 20 without bladder symptoms who served as controls. Evaluation included patient history, urinalysis, a voiding diary and urodynamic studies. Urine samples were collected. NGF, PGE2, PGF2alpha and PGI2 were measured using enzyme-linked immunosorbent assay and compared between the groups. In addition, correlations between urinary NGF and PG, and urodynamic parameters in patients with OAB were examined. RESULTS: Urinary NGF, PGE2 and PGF2alpha were significantly increased in patients with OAB compared with controls (p <0.05). However, urinary PGI2 was not different between controls and patients with OAB. In patients with OAB urinary PGE2 positively correlated with volume at first desire to void and maximum cystometric capacity (p <0.05). Urinary NGF, PGF2alpha and PGI2 did not correlate with urodynamic parameters in patients with OAB. CONCLUSIONS: NGF and PGs have important roles in the development of OAB symptoms in female patients. Urinary levels of these factors may be used as markers to evaluate OAB symptoms.
16600756	24	38	prostaglandins	Chemical	D011453
16600756	76	94	overactive bladder	Disease	D053201
16600756	113	116	PGs	Chemical	D011453
16600756	274	277	PGs	Chemical	D011453
16600756	292	295	OAB	Disease	D053201
16600756	360	363	OAB	Disease	D053201
16600756	544	548	PGE2	Chemical	D015232
16600756	550	559	PGF2alpha	Chemical	D015237
16600756	564	568	PGI2	Chemical	D011464
16600756	706	708	PG	Chemical	D011453
16600756	753	756	OAB	Disease	D053201
16600756	794	798	PGE2	Chemical	D015232
16600756	803	812	PGF2alpha	Chemical	D015237
16600756	859	862	OAB	Disease	D053201
16600756	914	918	PGI2	Chemical	D011464
16600756	972	975	OAB	Disease	D053201
16600756	994	997	OAB	Disease	D053201
16600756	1006	1010	PGE2	Chemical	D015232
16600756	1126	1135	PGF2alpha	Chemical	D015237
16600756	1140	1144	PGI2	Chemical	D011464
16600756	1207	1210	OAB	Disease	D053201
16600756	1233	1236	PGs	Chemical	D011453
16600756	1280	1283	OAB	Disease	D053201
16600756	1380	1383	OAB	Disease	D053201
16600756	CID	D015237	D053201
16600756	CID	D015232	D053201

15686794|t|Acute low back pain during intravenous administration of amiodarone: a report of two cases.
15686794|a|Amiodarone represents an effective antiarrhythmic drug for cardioversion of recent-onset atrial fibrillation (AF) and maintenance of sinus rhythm. We briefly describe two patients suffering from recent-onset atrial fibrillation, who experienced an acute devastating low back pain a few minutes after initiation of intravenous amiodarone loading. Notably, this side effect has not been ever reported in the medical literature. Clinicians should be aware of this reaction since prompt termination of parenteral administration leads to complete resolution.
15686794	6	19	low back pain	Disease	D017116
15686794	57	67	amiodarone	Chemical	D000638
15686794	92	102	Amiodarone	Chemical	D000638
15686794	181	200	atrial fibrillation	Disease	D001281
15686794	202	204	AF	Disease	D001281
15686794	300	319	atrial fibrillation	Disease	D001281
15686794	358	371	low back pain	Disease	D017116
15686794	418	428	amiodarone	Chemical	D000638
15686794	CID	D000638	D017116

12760988|t|Postoperative myalgia after succinylcholine: no evidence for an inflammatory origin.
12760988|a|A common side effect associated with succinylcholine is postoperative myalgia. The pathogenesis of this myalgia is still unclear; inflammation has been suggested but without convincing evidence. We designed the present study to investigate whether an inflammatory reaction contributes to this myalgia. The incidence and severity of succinylcholine-associated myalgia was determined in 64 patients pretreated with saline or dexamethasone before succinylcholine (n = 32 for each). Incidence and severity of myalgia did not differ significantly between the two groups: 15 patients in the dexamethasone group complained of myalgia compared with 18 patients in the saline group, and severe myalgia was reported by five patients and three patients, respectively (not significant). At 48 h after surgery, 12 patients in both groups still suffered from myalgia (not significant). In addition, interleukin-6 (IL-6) as an early marker of inflammation was assessed in a subgroup of 10 patients pretreated with saline. We found an increase of IL-6 for only three patients, but only one patient reported myalgia; no relationship between myalgia and the increase of IL-6 was found. In conclusion, there is no evidence for an inflammatory origin of succinylcholine-associated myalgia. IMPLICATIONS: Administration of dexamethasone before succinylcholine was not effective in decreasing the incidence or the severity of succinylcholine-induced postoperative myalgia. Furthermore, there was no significant relationship between postoperative myalgia and time course of interleukin-6 concentrations, a marker of inflammation. Pretreatment with dexamethasone is not justified to prevent postoperative myalgia after succinylcholine.
12760988	0	21	Postoperative myalgia	Disease	D010149
12760988	28	43	succinylcholine	Chemical	D013390
12760988	122	137	succinylcholine	Chemical	D013390
12760988	141	162	postoperative myalgia	Disease	D010149
12760988	189	196	myalgia	Disease	D063806
12760988	215	227	inflammation	Disease	D007249
12760988	378	385	myalgia	Disease	D063806
12760988	417	432	succinylcholine	Chemical	D013390
12760988	444	451	myalgia	Disease	D063806
12760988	508	521	dexamethasone	Chemical	D003907
12760988	529	544	succinylcholine	Chemical	D013390
12760988	590	597	myalgia	Disease	D063806
12760988	670	683	dexamethasone	Chemical	D003907
12760988	704	711	myalgia	Disease	D063806
12760988	770	777	myalgia	Disease	D063806
12760988	930	937	myalgia	Disease	D063806
12760988	1013	1025	inflammation	Disease	D007249
12760988	1176	1183	myalgia	Disease	D063806
12760988	1209	1216	myalgia	Disease	D063806
12760988	1319	1334	succinylcholine	Chemical	D013390
12760988	1346	1353	myalgia	Disease	D063806
12760988	1387	1400	dexamethasone	Chemical	D003907
12760988	1408	1423	succinylcholine	Chemical	D013390
12760988	1489	1504	succinylcholine	Chemical	D013390
12760988	1513	1534	postoperative myalgia	Disease	D010149
12760988	1595	1616	postoperative myalgia	Disease	D010149
12760988	1678	1690	inflammation	Disease	D007249
12760988	1710	1723	dexamethasone	Chemical	D003907
12760988	1752	1773	postoperative myalgia	Disease	D010149
12760988	1780	1795	succinylcholine	Chemical	D013390
12760988	CID	D013390	D010149
12760988	CID	D013390	D063806

12691807|t|Levodopa-induced oromandibular dystonia in progressive supranuclear palsy.
12691807|a|Levodopa-induced dyskinesias have been reported in Parkinson's disease and multiple system atrophy. Cranial dystonias are rare in patients with progressive supranuclear palsy (PSP). In this report we describe an unusual case of reversible levodopa-induced Oromandibular dystonia (OMD) in a PSP patient to highlight the importance of recognizing this drug related complication in the management of PSP, and discuss the possible underlying pathophysiology.
12691807	0	8	Levodopa	Chemical	D007980
12691807	31	39	dystonia	Disease	D004421
12691807	43	73	progressive supranuclear palsy	Disease	D013494
12691807	75	83	Levodopa	Chemical	D007980
12691807	92	103	dyskinesias	Disease	D004409
12691807	126	145	Parkinson's disease	Disease	D010300
12691807	150	173	multiple system atrophy	Disease	D019578
12691807	183	192	dystonias	Disease	D004421
12691807	219	249	progressive supranuclear palsy	Disease	D013494
12691807	251	254	PSP	Disease	D013494
12691807	314	322	levodopa	Chemical	D007980
12691807	331	353	Oromandibular dystonia	Disease	D008538
12691807	355	358	OMD	Disease	D008538
12691807	365	368	PSP	Disease	D013494
12691807	472	475	PSP	Disease	D013494
12691807	CID	D007980	D004421

12600698|t|Protective effect of edaravone against streptomycin-induced vestibulotoxicity in the guinea pig.
12600698|a|This study investigated alleviation of streptomycin-induced vestibulotoxicity by edaravone in guinea pigs. Edaravone, a free radical scavenger, has potent free radical quenching action and is used in clinical practice to treat cerebral infarction. Streptomycin was administered to the inner ear by osmotic pump for 24 h, and edaravone (n=8) or saline (n=6) was intraperitoneally injected once a day for 7 days. We observed horizontal vestibulo-ocular reflex as a marker of postoperative vestibular function. Animals injected with saline showed statistically smaller gains than those injected with edaravone. These results suggest that edaravone suppresses streptomycin-induced vestibulotoxicity.
12600698	21	30	edaravone	Chemical	C005435
12600698	39	51	streptomycin	Chemical	D013307
12600698	60	77	vestibulotoxicity	Disease	D015837
12600698	136	148	streptomycin	Chemical	D013307
12600698	157	174	vestibulotoxicity	Disease	D015837
12600698	178	187	edaravone	Chemical	C005435
12600698	204	213	Edaravone	Chemical	C005435
12600698	324	343	cerebral infarction	Disease	D002544
12600698	345	357	Streptomycin	Chemical	D013307
12600698	422	431	edaravone	Chemical	C005435
12600698	694	703	edaravone	Chemical	C005435
12600698	732	741	edaravone	Chemical	C005435
12600698	753	765	streptomycin	Chemical	D013307
12600698	774	791	vestibulotoxicity	Disease	D015837
12600698	CID	D013307	D015837

12091028|t|Ketamine in war/tropical surgery (a final tribute to the racemic mixture).
12091028|a|A technique of continuous intravenous anaesthesia with ketamine was used successfully during the Somalia civil war in 1994 and in north Uganda in 1999 for 64 operations in 62 patients, aged from 6 weeks to 70 years, undergoing limb and abdominal surgery including caesarian sections and interventions in neonates. Operations lasting up to 2h could be performed in the absence of sophisticated equipment such as pulse oximeters or ventilators in patients on spontaneous ventilation breathing air/oxygen only. After premedication with diazepam, glycopyrrolate and local anaesthesia, and induction with standard doses of ketamine, a maintenance dose of 10-20 microg/kg/min of ketamine proved safe and effective. Emphasis was placed on bedside clinical monitoring, relying heavily on the heart rate. Diazepam, unless contraindicated or risky, remains the only necessary complementary drug to ketamine as it buffers its cardiovascular response and decreases the duration and intensity of operative and postoperative hallucinations. Local anaesthetic blocks were useful in decreasing the requirement for postoperative analgesia. An antisialogue was usually unnecessary in operations lasting up to 2 h, glycopyrrolate being the best choice for its lowest psychotropic and chronotropic effects, especially in a hot climate. Experience in war/tropical settings suggests this technique could be useful in civilian contexts such as outdoor life-saving emergency surgery or in mass casualties where, e.g. amputation and rapid extrication were required.
12091028	0	8	Ketamine	Chemical	D007649
12091028	130	138	ketamine	Chemical	D007649
12091028	570	576	oxygen	Chemical	D010100
12091028	608	616	diazepam	Chemical	D003975
12091028	618	632	glycopyrrolate	Chemical	D006024
12091028	693	701	ketamine	Chemical	D007649
12091028	748	756	ketamine	Chemical	D007649
12091028	871	879	Diazepam	Chemical	D003975
12091028	963	971	ketamine	Chemical	D007649
12091028	1086	1100	hallucinations	Disease	D006212
12091028	1187	1196	analgesia	Disease	D000699
12091028	1271	1285	glycopyrrolate	Chemical	D006024
12091028	CID	D007649	D006212

11860495|t|Steroid structure and pharmacological properties determine the anti-amnesic effects of pregnenolone sulphate in the passive avoidance task in rats.
11860495|a|Pregnenolone sulphate (PREGS) has generated interest as one of the most potent memory-enhancing neurosteroids to be examined in rodent learning studies, with particular importance in the ageing process. The mechanism by which this endogenous steroid enhances memory formation is hypothesized to involve actions on glutamatergic and GABAergic systems. This hypothesis stems from findings that PREGS is a potent positive modulator of N-methyl-d-aspartate receptors (NMDARs) and a negative modulator of gamma-aminobutyric acid(A) receptors (GABA(A)Rs). Moreover, PREGS is able to reverse the amnesic-like effects of NMDAR and GABA(A)R ligands. To investigate this hypothesis, the present study in rats examined the memory-altering abilities of structural analogs of PREGS, which differ in their modulation of NMDAR and/or GABA(A)R function. The analogs tested were: 11-ketopregnenolone sulphate (an agent that is inactive at GABA(A)Rs and NMDARs), epipregnanolone ([3beta-hydroxy-5beta-pregnan-20-one] sulphate, an inhibitor of both GABA(A)Rs and NMDARs), and a newly synthesized (-) PREGS enantiomer (which is identical to PREGS in effects on GABA(A)Rs and NMDARs). The memory-enhancing effects of PREGS and its analogs were tested in the passive avoidance task using the model of scopolamine-induced amnesia. Both PREGS and its (-) enantiomer blocked the effects of scopolamine. The results show that, unlike PREGS, 11-ketopregnenolone sulphate and epipregnanolone sulphate failed to block the effect of scopolamine, suggesting that altering the modulation of NMDA receptors diminishes the memory-enhancing effects of PREGS. Moreover, enantioselectivity was demonstrated by the ability of natural PREGS to be an order of magnitude more effective than its synthetic enantiomer in reversing scopolamine-induced amnesia. These results identify a novel neuropharmacological site for the modulation of memory processes by neuroactive steroids.
11860495	0	7	Steroid	Chemical	D013256
11860495	68	75	amnesic	Disease	D000647
11860495	87	108	pregnenolone sulphate	Chemical	C018370
11860495	148	169	Pregnenolone sulphate	Chemical	C018370
11860495	171	176	PREGS	Chemical	C018370
11860495	390	397	steroid	Chemical	D013256
11860495	540	545	PREGS	Chemical	C018370
11860495	580	600	N-methyl-d-aspartate	Chemical	D016202
11860495	648	671	gamma-aminobutyric acid	Chemical	D005680
11860495	686	690	GABA	Chemical	D005680
11860495	708	713	PREGS	Chemical	C018370
11860495	737	744	amnesic	Disease	D000647
11860495	771	775	GABA	Chemical	D005680
11860495	911	916	PREGS	Chemical	C018370
11860495	967	971	GABA	Chemical	D005680
11860495	1011	1039	11-ketopregnenolone sulphate	Chemical	-1
11860495	1070	1074	GABA	Chemical	D005680
11860495	1093	1155	epipregnanolone ([3beta-hydroxy-5beta-pregnan-20-one] sulphate	Chemical	C018370
11860495	1178	1182	GABA	Chemical	D005680
11860495	1229	1234	PREGS	Chemical	C018370
11860495	1269	1274	PREGS	Chemical	C018370
11860495	1289	1293	GABA	Chemical	D005680
11860495	1344	1349	PREGS	Chemical	C018370
11860495	1427	1438	scopolamine	Chemical	D012601
11860495	1447	1454	amnesia	Disease	D000647
11860495	1461	1466	PREGS	Chemical	C018370
11860495	1513	1524	scopolamine	Chemical	D012601
11860495	1556	1561	PREGS	Chemical	C018370
11860495	1563	1591	11-ketopregnenolone sulphate	Chemical	-1
11860495	1596	1620	epipregnanolone sulphate	Chemical	C018370
11860495	1651	1662	scopolamine	Chemical	D012601
11860495	1707	1711	NMDA	Chemical	D016202
11860495	1765	1770	PREGS	Chemical	C018370
11860495	1844	1849	PREGS	Chemical	C018370
11860495	1936	1947	scopolamine	Chemical	D012601
11860495	1956	1963	amnesia	Disease	D000647
11860495	2076	2084	steroids	Chemical	D013256
11860495	CID	D012601	D000647

11752998|t|Preliminary efficacy assessment of intrathecal injection of an American formulation of adenosine in humans.
11752998|a|BACKGROUND: Preclinical studies of intrathecal adenosine suggest it may be effective in the treatment of acute and chronic pain in humans, and preliminary studies in volunteers and patients with a Swedish formulation of adenosine suggests it may be effective in hypersensitivity states but not with acute noxious stimulation. The purpose of this study was to screen for efficacy of a different formulation of adenosine marketed in the US, using both acute noxious stimulation and capsaicin-evoked mechanical hypersensitivity. METHODS: Following Food and Drug Administration and institutional review board approval and written informed consent, 65 volunteers were studied in two trials: an open-label, dose-escalating trial with intrathecal adenosine doses of 0.25-2.0 mg and a double-blind, placebo-controlled trial of adenosine, 2 mg. Cerebrospinal fluid was obtained for pharmacokinetic analysis, and pain ratings in response to acute heat stimuli and areas of mechanical hyperalgesia and allodynia after intradermal capsaicin injection were determined. RESULTS: Adenosine produced no effect on pain report to acute noxious thermal or chemical stimulation but reduced mechanical hyperalgesia and allodynia from intradermal capsaicin injection for at least 24 h. In contrast, residence time of adenosine in cerebrospinal fluid was short (< 4 h). CONCLUSIONS: These results show selective inhibition by intrathecal adenosine of hypersensitivity, presumed to reflect central sensitization in humans after peripheral capsaicin injection. The long-lasting effect is consistent with that observed in preliminary reports of patients with chronic neuropathic pain and is not due to prolonged residence of adenosine in cerebrospinal fluid.
11752998	87	96	adenosine	Chemical	D000241
11752998	155	164	adenosine	Chemical	D000241
11752998	213	235	acute and chronic pain	Disease	D059787|D059350	acute pain|chronic pain
11752998	328	337	adenosine	Chemical	D000241
11752998	370	386	hypersensitivity	Disease	D004342
11752998	517	526	adenosine	Chemical	D000241
11752998	588	597	capsaicin	Chemical	D002211
11752998	616	632	hypersensitivity	Disease	D004342
11752998	848	857	adenosine	Chemical	D000241
11752998	927	936	adenosine	Chemical	D000241
11752998	1011	1015	pain	Disease	D010146
11752998	1071	1094	mechanical hyperalgesia	Disease	D006930
11752998	1099	1108	allodynia	Disease	D006930
11752998	1127	1136	capsaicin	Chemical	D002211
11752998	1173	1182	Adenosine	Chemical	D000241
11752998	1205	1209	pain	Disease	D010146
11752998	1278	1301	mechanical hyperalgesia	Disease	D006930
11752998	1306	1315	allodynia	Disease	D006930
11752998	1333	1342	capsaicin	Chemical	D002211
11752998	1403	1412	adenosine	Chemical	D000241
11752998	1523	1532	adenosine	Chemical	D000241
11752998	1536	1552	hypersensitivity	Disease	D004342
11752998	1623	1632	capsaicin	Chemical	D002211
11752998	1749	1765	neuropathic pain	Disease	D009437
11752998	1807	1816	adenosine	Chemical	D000241
11752998	CID	D002211	D006930

10354657|t|Effect of lithium maintenance therapy on thyroid and parathyroid function.
10354657|a|OBJECTIVES: To assess changes induced by lithium maintenance therapy on the incidence of thyroid, parathyroid and ion alterations. These were evaluated with respect to the duration of lithium therapy, age, sex, and family history (whether or not the patient had a first-degree relative with thyroid disease). DESIGN: Prospective study. SETTING: Affective Disorders Clinic at St. Mary's Hospital, Montreal. PATIENTS: One hundred and one patients (28 men and 73 women) with bipolar disorder receiving lithium maintenance therapy ranging from 1 year's to 32 years' duration. The control group consisted of 82 patients with no psychiatric or endocrinological diagnoses from the hospital's out-patient clinics. OUTCOME MEASURES: Laboratory analyses of calcium, magnesium and thyroid-stimulating hormone levels performed before beginning lithium therapy and at biannual follow-up. RESULTS: Hypothyroidism developed in 40 patients, excluding 8 patients who were hypothyroid at baseline. All patients having first-degree relatives affected by thyroid illness had accelerated onset of hypothyroidism (3.7 years after onset of lithium therapy) compared with patients without a family history (8.6 years after onset of lithium therapy). Women over 60 years of age were more often affected by hypothyroidism than women under 60 years of age (34.6% versus 31.9%). Magnesium levels in patients on lithium treatment were unchanged from baseline levels. After lithium treatment, calcium levels were higher than either baseline levels or control levels. Thus, lithium treatment counteracted the decrease in plasma calcium levels associated with aging. CONCLUSIONS: Familial thyroid illness is a risk factor for hypothyroidism and hypercalcemia during lithium therapy.
10354657	10	17	lithium	Chemical	D008094
10354657	116	123	lithium	Chemical	D008094
10354657	259	266	lithium	Chemical	D008094
10354657	366	381	thyroid disease	Disease	D013959
10354657	547	563	bipolar disorder	Disease	D001714
10354657	574	581	lithium	Chemical	D008094
10354657	698	709	psychiatric	Disease	D001523
10354657	822	829	calcium	Chemical	D002118
10354657	831	840	magnesium	Chemical	D008274
10354657	907	914	lithium	Chemical	D008094
10354657	959	973	Hypothyroidism	Disease	D007037
10354657	1030	1041	hypothyroid	Disease	D007037
10354657	1110	1125	thyroid illness	Disease	D013959
10354657	1151	1165	hypothyroidism	Disease	D007037
10354657	1192	1199	lithium	Chemical	D008094
10354657	1283	1290	lithium	Chemical	D008094
10354657	1356	1370	hypothyroidism	Disease	D007037
10354657	1426	1435	Magnesium	Chemical	D008274
10354657	1458	1465	lithium	Chemical	D008094
10354657	1519	1526	lithium	Chemical	D008094
10354657	1538	1545	calcium	Chemical	D002118
10354657	1618	1625	lithium	Chemical	D008094
10354657	1672	1679	calcium	Chemical	D002118
10354657	1732	1747	thyroid illness	Disease	D013959
10354657	1769	1783	hypothyroidism	Disease	D007037
10354657	1788	1801	hypercalcemia	Disease	D006934
10354657	1809	1816	lithium	Chemical	D008094
10354657	CID	D008094	D007037

10328196|t|Systemic toxicity following administration of sirolimus (formerly rapamycin) for psoriasis: association of capillary leak syndrome with apoptosis of lesional lymphocytes.
10328196|a|BACKGROUND: Sirolimus (formerly rapamycin) is an immunosuppressive agent that interferes with T-cell activation. After 2 individuals with psoriasis developed a capillary leak syndrome following treatment with oral sirolimus lesional skin cells and activated peripheral blood cells were analyzed for induction of apoptosis. OBSERVATIONS: A keratome skin specimen from 1 patient with sirolimus-induced capillary leak syndrome had a 2.3-fold increase in percentage of apoptotic cells (to 48%) compared with an unaffected sirolimus-treated patient with psoriasis (21%). Activated peripheral blood T cells from patients with psoriasis tended to exhibit greater spontaneous or dexamethasone-induced apoptosis than did normal T cells, particularly in the presence of sirolimus. CONCLUSIONS: Severe adverse effects of sirolimus include fever, anemia, and capillary leak syndrome. These symptoms may be the result of drug-induced apoptosis of lesional leukocytes, especially activated T lymphocytes, and possibly release of inflammatory mediators. Because patients with severe psoriasis may develop capillary leak from various systemic therapies, clinical monitoring is advisable for patients with inflammatory diseases who are treated with immune modulators.
10328196	9	17	toxicity	Disease	D064420
10328196	46	55	sirolimus	Chemical	D020123
10328196	66	75	rapamycin	Chemical	D020123
10328196	81	90	psoriasis	Disease	D011565
10328196	107	130	capillary leak syndrome	Disease	D019559
10328196	183	192	Sirolimus	Chemical	D020123
10328196	203	212	rapamycin	Chemical	D020123
10328196	309	318	psoriasis	Disease	D011565
10328196	331	354	capillary leak syndrome	Disease	D019559
10328196	385	394	sirolimus	Chemical	D020123
10328196	553	562	sirolimus	Chemical	D020123
10328196	571	594	capillary leak syndrome	Disease	D019559
10328196	689	698	sirolimus	Chemical	D020123
10328196	720	729	psoriasis	Disease	D011565
10328196	791	800	psoriasis	Disease	D011565
10328196	842	855	dexamethasone	Chemical	D003907
10328196	931	940	sirolimus	Chemical	D020123
10328196	981	990	sirolimus	Chemical	D020123
10328196	999	1004	fever	Disease	D005334
10328196	1006	1012	anemia	Disease	D000740
10328196	1018	1041	capillary leak syndrome	Disease	D019559
10328196	1239	1248	psoriasis	Disease	D011565
10328196	1261	1275	capillary leak	Disease	D019559
10328196	1360	1381	inflammatory diseases	Disease	D007249
10328196	CID	D020123	D019559

9630698|t|Contribution of the glycine site of NMDA receptors in rostral and intermediate-caudal parts of the striatum to the regulation of muscle tone in rats.
9630698|a|The aim of the present study was to assess the contribution of the glycine site of NMDA receptors in the striatum to the regulation of muscle tone. Muscle tone was examined using a combined mechanoand electromyographic method, which measured simultaneously the muscle resistance (MMG) of the rat's hind foot to passive extension and flexion in the ankle joint and the electromyographic activity (EMG) of the antagonistic muscles of that joint: gastrocnemius and tibialis anterior. Muscle rigidity was induced by haloperidol (2.5 mg/kg i.p.). 5,7-dichlorokynurenic acid (5,7-DCKA), a selective glycine site antagonist, injected in doses of 2.5 and 4.5 microg/0.5 microl bilaterally, into the rostral region of the striatum, decreased both the haloperidol-induced muscle rigidity (MMG) and the enhanced electromyographic activity (EMG). 5,7-DCKA injected bilaterally in a dose of 4.5 microg/0.5 microl into the intermediate-caudal region of the striatum of rats not pretreated with haloperidol had no effect on the muscle tone. The present results suggest that blockade of the glycine site of NMDA receptors in the rostral part of the striatum may be mainly responsible for the antiparkinsonian action of this drug.
9630698	20	27	glycine	Chemical	D005998
9630698	36	40	NMDA	Chemical	D016202
9630698	217	224	glycine	Chemical	D005998
9630698	233	237	NMDA	Chemical	D016202
9630698	631	646	Muscle rigidity	Disease	D009127
9630698	662	673	haloperidol	Chemical	D006220
9630698	692	718	5,7-dichlorokynurenic acid	Chemical	C066192
9630698	720	728	5,7-DCKA	Chemical	C066192
9630698	743	750	glycine	Chemical	D005998
9630698	892	903	haloperidol	Chemical	D006220
9630698	912	927	muscle rigidity	Disease	D009127
9630698	985	993	5,7-DCKA	Chemical	C066192
9630698	1130	1141	haloperidol	Chemical	D006220
9630698	1225	1232	glycine	Chemical	D005998
9630698	1241	1245	NMDA	Chemical	D016202
9630698	CID	D006220	D009127

8480959|t|Efficacy and tolerability of lovastatin in 3390 women with moderate hypercholesterolemia.
8480959|a|OBJECTIVE: To evaluate the efficacy and safety of lovastatin in women with moderate hypercholesterolemia. DESIGN: The Expanded Clinical Evaluation of Lovastatin (EXCEL) Study, a multicenter, double-blind, diet- and placebo-controlled trial, in which participants were randomly assigned to receive placebo or lovastatin at doses of 20 or 40 mg once daily, or 20 or 40 mg twice daily for 48 weeks. SETTING: Ambulatory patients recruited by 362 participating centers throughout the United States. PATIENTS: Women (n = 3390) from the total cohort of 8245 volunteers. MEASUREMENTS: Plasma total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, and triglycerides; and laboratory and clinical evidence of adverse events monitored periodically throughout the study. RESULTS: Among women, lovastatin (20 to 80 mg/d) produced sustained (12- to 48-week), dose-related changes (P < 0.001): decreases in LDL cholesterol (24% to 40%) and triglycerides (9% to 18%), and increases in HDL cholesterol (6.7% to 8.6%). Depending on the dose, from 82% to 95% of lovastatin-treated women achieved the National Cholesterol Education Program goal of LDL cholesterol levels less than 4.14 mmol/L (160 mg/dL), and 40% to 87% achieved the goal of 3.36 mmol/L (130 mg/dL). Successive transaminase elevations greater than three times the upper limit of normal occurred in 0.1% of women and were dose dependent above the 20-mg dose. Myopathy, defined as muscle symptoms with creatine kinase elevations greater than 10 times the upper limit of normal, was rare and associated with the highest recommended daily dose of lovastatin (80 mg). Estrogen-replacement therapy appeared to have no effect on either the efficacy or safety profile of lovastatin. CONCLUSION: Lovastatin is highly effective and generally well tolerated as therapy for primary hypercholesterolemia in women.
8480959	29	39	lovastatin	Chemical	D008148
8480959	68	88	hypercholesterolemia	Disease	D006937
8480959	140	150	lovastatin	Chemical	D008148
8480959	174	194	hypercholesterolemia	Disease	D006937
8480959	240	250	Lovastatin	Chemical	D008148
8480959	398	408	lovastatin	Chemical	D008148
8480959	747	758	cholesterol	Chemical	D002784
8480959	764	777	triglycerides	Chemical	D014280
8480959	901	911	lovastatin	Chemical	D008148
8480959	1016	1027	cholesterol	Chemical	D002784
8480959	1045	1058	triglycerides	Chemical	D014280
8480959	1093	1104	cholesterol	Chemical	D002784
8480959	1163	1173	lovastatin	Chemical	D008148
8480959	1210	1221	Cholesterol	Chemical	D002784
8480959	1252	1263	cholesterol	Chemical	D002784
8480959	1525	1533	Myopathy	Disease	D009135
8480959	1567	1575	creatine	Chemical	D003401
8480959	1710	1720	lovastatin	Chemical	D008148
8480959	1830	1840	lovastatin	Chemical	D008148
8480959	1854	1864	Lovastatin	Chemical	D008148
8480959	1937	1957	hypercholesterolemia	Disease	D006937
8480959	CID	D008148	D009135

7197363|t|REM sleep deprivation changes behavioral response to catecholaminergic and serotonergic receptor activation in rats.
7197363|a|The effects of REM sleep deprivation (REMD) on apomorphine-induced aggressiveness and quipazine-induced head twitches in rats were determined. Forty-eight hr of REMD increased apomorphine-induced aggressiveness, and reduced (immediately after completing of REMD) or increased (96 hr after completing of REMD) quipazine-induced head twitches. Results are discussed in terms of similarity to pharmacological effects of other antidepressive treatments.
7197363	0	21	REM sleep deprivation	Disease	D012892
7197363	132	153	REM sleep deprivation	Disease	D012892
7197363	155	159	REMD	Disease	D012892
7197363	164	175	apomorphine	Chemical	D001058
7197363	184	198	aggressiveness	Disease	D001523
7197363	203	212	quipazine	Chemical	D011814
7197363	221	234	head twitches	Disease	D009069
7197363	278	282	REMD	Disease	D012892
7197363	293	304	apomorphine	Chemical	D001058
7197363	313	327	aggressiveness	Disease	D001523
7197363	374	378	REMD	Disease	D012892
7197363	420	424	REMD	Disease	D012892
7197363	426	435	quipazine	Chemical	D011814
7197363	444	457	head twitches	Disease	D009069
7197363	CID	D011814	D009069
7197363	CID	D001058	D001523

7161250|t|Extrapyramidal side effects and oral haloperidol: an analysis of explanatory patient and treatment characteristics.
7161250|a|The incidence of extrapyramidal side effects (EPS) was evaluated in 98 patients treated with haloperidol. The incidence of parkinsonism was higher at higher doses of haloperidol and in younger patients. Prophylactic antiparkinsonian medication was effective in younger but not in older patients. However, these medications were more effective in both young and old patients when given after parkinsonism developed. Akathisia was controlled by the benzodiazepine lorazepam in 14 out of 16 patients, while prophylactic antiparkinsonians were ineffective. The present study points to patient characteristics that may be of significance in the development of EPS due to haloperidol.
7161250	37	48	haloperidol	Chemical	D006220
7161250	209	220	haloperidol	Chemical	D006220
7161250	239	251	parkinsonism	Disease	D010302
7161250	282	293	haloperidol	Chemical	D006220
7161250	507	519	parkinsonism	Disease	D010302
7161250	531	540	Akathisia	Disease	D017109
7161250	563	577	benzodiazepine	Chemical	D001569
7161250	578	587	lorazepam	Chemical	D008140
7161250	782	793	haloperidol	Chemical	D006220
7161250	CID	D006220	D010302

7053705|t|Hepatic veno-occlusive disease caused by 6-thioguanine.
7053705|a|Clinically reversible veno-occlusive disease of the liver developed in a 23-year-old man with acute lymphocytic leukemia after 10 months of maintenance therapy with 6-thioguanine. Serial liver biopsies showed the development and resolution of intense sinusoidal engorgement. Although this disease was clinically reversible, some subintimal fibrosis about the terminal hepatic veins persisted. This case presented a unique opportunity to observe the histologic features of clinically reversible hepatic veno-occlusive disease over time, and may be the first case of veno-occlusive related solely to 6-thioguanine.
7053705	0	30	Hepatic veno-occlusive disease	Disease	D006504
7053705	41	54	6-thioguanine	Chemical	D013866
7053705	78	113	veno-occlusive disease of the liver	Disease	D006504
7053705	150	176	acute lymphocytic leukemia	Disease	D054198
7053705	221	234	6-thioguanine	Chemical	D013866
7053705	396	404	fibrosis	Disease	D005355
7053705	550	580	hepatic veno-occlusive disease	Disease	D006504
7053705	654	667	6-thioguanine	Chemical	D013866
7053705	CID	D013866	D006504

6402369|t|Treatment of ifosfamide-induced urothelial toxicity by oral administration of sodium 2-mercaptoethane sulphonate (MESNA) to patients with inoperable lung cancer.
6402369|a|The protective effect of oral administration of the thiol compound sodium 2-mercaptoethane sulphonate (MESNA) against urothelial toxicity induced by ifosfamide (IF) was tested in a group of 45 patients with inoperable lung cancer under treatment with IF (2250 mg/m2 on days 2-5) as part of a polychemotherapy regimen repeated in a 4-week cycle. MESNA was given orally on the days of treatment with IF in 3 doses of 840 mg/m2, each administered at 0 hr (= injection of IF), 4 hr and 8 hr p.i. Out of a total of 88 courses of this treatment we observed 10 episodes of asymptomatic microscopic haematuria and no episodes of gross haematuria. In this group of 45 patients under protection with MESNA there were 5 complete remissions and 9 partial remissions (total 31%). A further group of 25 patients under polychemotherapy with IF were treated by conventional prophylactic measures (raised fluid intake and forced diuresis). In this group there were 1 complete and 5 partial remissions (total 24%), but nearly all patients developed either gross haematuria and/or symptoms of bladder irritation (cystitis and pollakisuria). There were no appreciable differences between the MESNA series and the conventional prophylaxis series with respect to either haematological or systemic toxicity of the cytostatic treatment. Our results support the view that MESNA, given orally in conjunction with combined cytostatic regimens which include IF, simplifies the treatment and provides optimum protection for the urinary epithelium. Protection with oral MESNA is particularly suitable for outpatients.
6402369	13	23	ifosfamide	Chemical	D007069
6402369	32	51	urothelial toxicity	Disease	D001745
6402369	78	112	sodium 2-mercaptoethane sulphonate	Chemical	D015080
6402369	114	119	MESNA	Chemical	D015080
6402369	149	160	lung cancer	Disease	D008175
6402369	214	219	thiol	Chemical	D013438
6402369	229	263	sodium 2-mercaptoethane sulphonate	Chemical	D015080
6402369	265	270	MESNA	Chemical	D015080
6402369	280	299	urothelial toxicity	Disease	D001745
6402369	311	321	ifosfamide	Chemical	D007069
6402369	323	325	IF	Chemical	D007069
6402369	380	391	lung cancer	Disease	D008175
6402369	413	415	IF	Chemical	D007069
6402369	507	512	MESNA	Chemical	D015080
6402369	560	562	IF	Chemical	D007069
6402369	630	632	IF	Chemical	D007069
6402369	753	763	haematuria	Disease	D006417
6402369	789	799	haematuria	Disease	D006417
6402369	852	857	MESNA	Chemical	D015080
6402369	988	990	IF	Chemical	D007069
6402369	1206	1216	haematuria	Disease	D006417
6402369	1236	1254	bladder irritation	Disease	D001745
6402369	1256	1264	cystitis	Disease	D003556
6402369	1269	1281	pollakisuria	Disease	D014555
6402369	1334	1339	MESNA	Chemical	D015080
6402369	1437	1445	toxicity	Disease	D064420
6402369	1509	1514	MESNA	Chemical	D015080
6402369	1592	1594	IF	Chemical	D007069
6402369	1702	1707	MESNA	Chemical	D015080
6402369	CID	D007069	D001745

3973521|t|Time course alterations of QTC interval due to hypaque 76.
3973521|a|Sequential measurement of QT interval during left ventricular angiography was made 30 seconds and one, three, five and ten minutes after injection of hypaque 76. The subjects were ten patients found to have normal left ventricles and coronary arteries. Significant QTC prolongation occurred in 30 seconds to one minute in association with marked hypotension and elevation of cardiac output.
3973521	47	57	hypaque 76	Chemical	C027278
3973521	209	219	hypaque 76	Chemical	C027278
3973521	324	340	QTC prolongation	Disease	D008133
3973521	405	416	hypotension	Disease	D007022
3973521	CID	C027278	D007022
3973521	CID	C027278	D008133

3461217|t|Production of autochthonous prostate cancer in Lobund-Wistar rats by treatments with N-nitroso-N-methylurea and testosterone.
3461217|a|More than 50% of Lobund-Wistar (L-W) strain rats developed large, palpable prostate adenocarcinomas (PAs) following treatments with N-nitroso-N-methylurea (CAS: 684-93-5) and testosterone propionate [(TP) CAS: 57-85-2], and most of the tumor-bearing rats manifested metastatic lesions. The incubation periods averaged 10.6 months. Within the same timeframe, no L-W rat developed a similar palpable PA when treated only with TP. In L-W rats, TP acted as a tumor enhancement agent, with primary emphasis on the development of prostate cancer.
3461217	28	43	prostate cancer	Disease	D011471
3461217	85	107	N-nitroso-N-methylurea	Chemical	D008770
3461217	112	124	testosterone	Chemical	D013739
3461217	201	225	prostate adenocarcinomas	Disease	D011471
3461217	227	230	PAs	Disease	D011471
3461217	258	280	N-nitroso-N-methylurea	Chemical	D008770
3461217	301	324	testosterone propionate	Chemical	D043343
3461217	327	329	TP	Chemical	D043343
3461217	362	367	tumor	Disease	D009369
3461217	524	526	PA	Disease	D011471
3461217	550	552	TP	Chemical	D043343
3461217	567	569	TP	Chemical	D043343
3461217	581	586	tumor	Disease	D009369
3461217	650	665	prostate cancer	Disease	D011471
3461217	CID	D043343	D011471
3461217	CID	D008770	D011471

2840807|t|A dystonia-like syndrome after neuropeptide (MSH/ACTH) stimulation of the rat locus ceruleus.
2840807|a|The movement disorder investigated in these studies has some features in common with human idiopathic dystonia, and information obtained in these studies may be of potential clinical benefit. The present experimental results indicated that peptidergic stimulation of the LC resulted in a NE-mediated inhibition of cerebellar Purkinje cells located at terminals of the ceruleo-cerebellar pathway. However, it is not certain as to the following: (a) what receptors were stimulated by the ACTH N-terminal fragments at the LC that resulted in this disorder; (b) whether NE, released onto Purkinje cell synapses located at terminals of the ceruleo-cerebellar pathway, did indeed cause the long-term depression at Purkinje cell synapses (previously described by others) that resulted in the long duration of the movement disorder; (c) whether the inhibition of inhibitory Purkinje cells resulted in disinhibition or increased excitability of the unilateral cerebellar fastigial or interpositus nuclei, the output targets of the Purkinje cell axons, that may have been an important contributing factor to this disorder. These questions are currently being investigated.
2840807	2	10	dystonia	Disease	D004421
2840807	45	48	MSH	Chemical	D009074
2840807	49	53	ACTH	Chemical	D000324
2840807	98	115	movement disorder	Disease	D009069
2840807	196	204	dystonia	Disease	D004421
2840807	580	584	ACTH	Chemical	D000324
2840807	788	798	depression	Disease	D003866
2840807	900	917	movement disorder	Disease	D009069
2840807	CID	D009074	D004421
2840807	CID	D000324	D004421

2569282|t|Dexmedetomidine, acting through central alpha-2 adrenoceptors, prevents opiate-induced muscle rigidity in the rat.
2569282|a|The highly-selective alpha-2 adrenergic agonist dexmedetomidine (D-MED) is capable of inducing muscle flaccidity and anesthesia in rats and dogs. Intense generalized muscle rigidity is an undesirable side effect of potent opiate agonists. Although the neurochemistry of opiate-induced rigidity has yet to be fully elucidated, recent work suggests a role for a central adrenergic mechanism. In the present study, the authors determined if treatment with D-MED prevents the muscle rigidity caused by high-dose alfentanil anesthesia in the rat. Animals (n = 42) were treated intraperitoneally with one of the following six regimens: 1) L-MED (the inactive L-isomer of medetomidine), 30 micrograms/kg; 2) D-MED, 10 micrograms/kg; 3) D-MED, 30 micrograms/kg; 4) D-MED [30 micrograms/kg] and the central-acting alpha-2 antagonist, idazoxan [10 mg/kg]; 5) D-MED [30 micrograms/kg] and the peripheral-acting alpha-2 antagonist DG-5128 [10 mg/kg], or; 6) saline. Baseline electromyographic activity was recorded from the gastrocnemius muscle before and after drug treatment. Each rat was then injected with alfentanil (ALF, 0.5 mg/kg sc). ALF injection resulted in a marked increase in hindlimb EMG activity in the L-MED treatment group which was indistinguishable from that seen in animals treated with saline. In contrast, D-MED prevented alfentanil-induced muscle rigidity in a dose-dependent fashion. The small EMG values obtained in the high-dose D-MED group were comparable with those recorded in earlier studies from control animals not given any opiate. The high-dose D-MED animals were flaccid, akinetic, and lacked a startle response during the entire experimental period.(ABSTRACT TRUNCATED AT 250 WORDS)
2569282	0	15	Dexmedetomidine	Chemical	D020927
2569282	87	102	muscle rigidity	Disease	D009127
2569282	163	178	dexmedetomidine	Chemical	D020927
2569282	180	185	D-MED	Chemical	D020927
2569282	210	227	muscle flaccidity	Disease	D009123
2569282	281	296	muscle rigidity	Disease	D009127
2569282	400	408	rigidity	Disease	D009127
2569282	568	573	D-MED	Chemical	D020927
2569282	587	602	muscle rigidity	Disease	D009127
2569282	623	633	alfentanil	Chemical	D015760
2569282	780	792	medetomidine	Chemical	D020926
2569282	816	821	D-MED	Chemical	D020927
2569282	844	849	D-MED	Chemical	D020927
2569282	872	877	D-MED	Chemical	D020927
2569282	940	948	idazoxan	Chemical	D019329
2569282	964	969	D-MED	Chemical	D020927
2569282	1034	1041	DG-5128	Chemical	C032368
2569282	1213	1223	alfentanil	Chemical	D015760
2569282	1225	1228	ALF	Chemical	D015760
2569282	1245	1248	ALF	Chemical	D015760
2569282	1431	1436	D-MED	Chemical	D020927
2569282	1447	1457	alfentanil	Chemical	D015760
2569282	1466	1481	muscle rigidity	Disease	D009127
2569282	1558	1563	D-MED	Chemical	D020927
2569282	1682	1687	D-MED	Chemical	D020927
2569282	1710	1718	akinetic	Disease	D018476
2569282	1733	1740	startle	Disease	D012021
2569282	CID	D015760	D009127

2343592|t|Seizure activity with imipenem therapy: incidence and risk factors.
2343592|a|Two elderly patients with a history of either cerebral vascular accident (CVA) or head trauma and no evidence of renal disease developed seizures while receiving maximum doses of imipenem/cilastatin. Neither patient had reported previous seizures or seizure-like activity nor was receiving anticonvulsant agents. All seizures were controlled with therapeutic doses of phenytoin. Both patients had received maximum doses of other beta-lactam antibiotics without evidence of seizure activity.
2343592	0	7	Seizure	Disease	D012640
2343592	22	30	imipenem	Chemical	D015378
2343592	114	140	cerebral vascular accident	Disease	D020521
2343592	142	145	CVA	Disease	D020521
2343592	150	161	head trauma	Disease	D006259
2343592	181	194	renal disease	Disease	D007674
2343592	205	213	seizures	Disease	D012640
2343592	247	266	imipenem/cilastatin	Chemical	C044650
2343592	306	314	seizures	Disease	D012640
2343592	318	325	seizure	Disease	D012640
2343592	385	393	seizures	Disease	D012640
2343592	436	445	phenytoin	Chemical	D010672
2343592	497	508	beta-lactam	Chemical	D047090
2343592	541	548	seizure	Disease	D012640
2343592	CID	C044650	D012640

2055425|t|The ability of insulin treatment to reverse or prevent the changes in urinary bladder function caused by streptozotocin-induced diabetes mellitus.
2055425|a|1. The effects of insulin treatment on in vivo and in vitro urinary bladder function in streptozotocin-diabetic rats were investigated. 2. Diabetes of 2 months duration resulted in decreases in body weight and increases in fluid consumption, urine volume, frequency of micturition, and average volume per micturition; effects which were prevented by insulin treatment. 3. Insulin treatment also prevented the increases in contractile responses of bladder body strips from diabetic rats to nerve stimulation, ATP, and bethanechol. 4. Diabetes of 4 months duration also resulted in decreases in body weight, and increases in fluid consumption, urine volume, frequency of micturition, and average volume per micturition, effects which were reversed by insulin treatment for the final 2 months of the study. 5. Insulin treatment reversed the increases in contractile responses of bladder body strips from diabetic rats to nerve stimulation, ATP, and bethanechol. 6. The data indicate that the effects of streptozotocin-induced diabetes on urinary bladder function are both prevented and reversed by insulin treatment.
2055425	105	119	streptozotocin	Chemical	D013311
2055425	128	145	diabetes mellitus	Disease	D003920
2055425	235	249	streptozotocin	Chemical	D013311
2055425	250	258	diabetic	Disease	D003920
2055425	286	294	Diabetes	Disease	D003920
2055425	619	627	diabetic	Disease	D003920
2055425	655	658	ATP	Chemical	D000255
2055425	664	675	bethanechol	Chemical	D018723
2055425	680	688	Diabetes	Disease	D003920
2055425	1048	1056	diabetic	Disease	D003920
2055425	1084	1087	ATP	Chemical	D000255
2055425	1093	1104	bethanechol	Chemical	D018723
2055425	1147	1161	streptozotocin	Chemical	D013311
2055425	1170	1178	diabetes	Disease	D003920
2055425	CID	D013311	D003920

1711760|t|Delayed institution of hypertension during focal cerebral ischemia: effect on brain edema.
1711760|a|The effect of induced hypertension instituted after a 2-h delay following middle cerebral artery occlusion (MCAO) on brain edema formation and histochemical injury was studied. Under isoflurane anesthesia, the MCA of 14 spontaneously hypertensive rats was occluded. In the control group (n = 7), the mean arterial pressure (MAP) was not manipulated. In the hypertensive group (n = 7), the MAP was elevated by 25-30 mm Hg beginning 2 h after MCAO. Four hours after MCAO, the rats were killed and the brains harvested. The brains were sectioned along coronal planes spanning the distribution of ischemia produced by MCAO. Specific gravity (SG) was determined in the subcortex and in two sites in the cortex (core and periphery of the ischemic territory). The extent of neuronal injury was determined by 2,3,5-triphenyltetrazolium staining. In the ischemic core, there was no difference in SG in the subcortex and cortex in the two groups. In the periphery of the ischemic territory, SG in the cortex was greater (less edema accumulation) in the hypertensive group (1.041 +/- 0.001 vs 1.039 +/- 0.001, P less than 0.05). The area of histochemical injury (as a percent of the cross-sectional area of the hemisphere) was less in the hypertensive group (33 +/- 3% vs 21 +/- 2%, P less than 0.05). The data indicate that phenylephrine-induced hypertension instituted 2 h after MCAO does not aggravate edema in the ischemic core, that it improves edema in the periphery of the ischemic territory, and that it reduces the area of histochemical neuronal dysfunction.
1711760	23	35	hypertension	Disease	D006973
1711760	49	66	cerebral ischemia	Disease	D002545
1711760	78	89	brain edema	Disease	D001929
1711760	113	125	hypertension	Disease	D006973
1711760	165	197	middle cerebral artery occlusion	Disease	D020244
1711760	199	203	MCAO	Disease	D020244
1711760	208	219	brain edema	Disease	D001929
1711760	274	284	isoflurane	Chemical	D007530
1711760	325	337	hypertensive	Disease	D006973
1711760	448	460	hypertensive	Disease	D006973
1711760	532	536	MCAO	Disease	D020244
1711760	555	559	MCAO	Disease	D020244
1711760	684	692	ischemia	Disease	D007511
1711760	705	709	MCAO	Disease	D020244
1711760	823	831	ischemic	Disease	D007511
1711760	858	873	neuronal injury	Disease	D009410
1711760	892	918	2,3,5-triphenyltetrazolium	Chemical	C009591
1711760	936	944	ischemic	Disease	D007511
1711760	1052	1060	ischemic	Disease	D007511
1711760	1107	1112	edema	Disease	D004487
1711760	1134	1146	hypertensive	Disease	D006973
1711760	1319	1331	hypertensive	Disease	D006973
1711760	1405	1418	phenylephrine	Chemical	D010656
1711760	1427	1439	hypertension	Disease	D006973
1711760	1461	1465	MCAO	Disease	D020244
1711760	1485	1490	edema	Disease	D004487
1711760	1498	1506	ischemic	Disease	D007511
1711760	1530	1535	edema	Disease	D004487
1711760	1560	1568	ischemic	Disease	D007511
1711760	1626	1646	neuronal dysfunction	Disease	D009410
1711760	CID	D010656	D006973

1595783|t|Amiodarone pulmonary toxicity.
1595783|a|Amiodarone is an effective antiarrhythmic agent whose utility is limited by many side-effects, the most problematic being pneumonitis. The pulmonary toxicity of amiodarone is thought to result from direct injury related to the intracellular accumulation of phospholipid and T cell-mediated hypersensitivity pneumonitis. The clinical and radiographic features of amiodarone-induced pulmonary toxicity are characteristic but nonspecific. The diagnosis depends on exclusion of other entities, such as heart failure, infection, and malignancy. While withdrawal of amiodarone leads to clinical improvement in majority of cases, this is not always possible or advisable. Dose reduction or concomitant steroid therapy may have a role in selected patients.
1595783	0	10	Amiodarone	Chemical	D000638
1595783	11	29	pulmonary toxicity	Disease	D008171
1595783	31	41	Amiodarone	Chemical	D000638
1595783	153	164	pneumonitis	Disease	D011014
1595783	170	188	pulmonary toxicity	Disease	D008171
1595783	192	202	amiodarone	Chemical	D000638
1595783	321	349	hypersensitivity pneumonitis	Disease	D004342|D000542	hypersensitivity|pneumonitis
1595783	393	403	amiodarone	Chemical	D000638
1595783	412	430	pulmonary toxicity	Disease	D008171
1595783	529	542	heart failure	Disease	D006333
1595783	544	553	infection	Disease	D007239
1595783	559	569	malignancy	Disease	D009369
1595783	591	601	amiodarone	Chemical	D000638
1595783	726	733	steroid	Chemical	D013256
1595783	CID	D000638	D011014
1595783	CID	D000638	D004342

804391|t|Light chain proteinuria and cellular mediated immunity in rifampin treated patients with tuberculosis.
804391|a|Light chain proteinuria was found in 9 of 17 tuberculosis patients treated with rifampin. Concomitant assay of cellular mediated immunity in these patients using skin test antigen and a lymphokine in vitro test provided results that were different. Response to Varidase skin test antigen was negative for all eight tuberculosis patients tested, but there occurred a hyper-responsiveness of the lymphocytes of these eight patients to phytomitogen (PHA-P). as well as of those of seven other tuberculous patients. This last finding may be related to time of testing and/or endogenous serum binding of rifampin which could have inhibited mitogen activity for the lymphocyte.
804391	12	23	proteinuria	Disease	D011507
804391	58	66	rifampin	Chemical	D012293
804391	89	101	tuberculosis	Disease	D014376
804391	115	126	proteinuria	Disease	D011507
804391	148	160	tuberculosis	Disease	D014376
804391	183	191	rifampin	Chemical	D012293
804391	418	430	tuberculosis	Disease	D014376
804391	593	604	tuberculous	Disease	D014376
804391	702	710	rifampin	Chemical	D012293
804391	CID	D012293	D011507

28952|t|Initial potassium loss and hypokalaemia during chlorthalidone administration in patients with essential hypertension: the influence of dietary sodium restriction.
28952|a|To investigate the initial potassium loss and development of hypokalaemia during the administration of an oral diuretic, metabolic balance studies were performed in ten patients with essential hypertension who had shown hypokalaemia under prior oral diuretic treatment. Chlorthalidone (50 mg daily) was given for 14 days. Six patients received a normal-sodium diet and four a low-sodium (17 mmol/day) diet. All patients had a normal initial total body potassium (40K). The electrolyte balances, weight, bromide space, plasma renin activity, and aldosterone secretion rate were measured. In both groups a potassium deficit developed, with proportionally larger losses from the extracellular than from the intracellular compartment. In the normal-sodium group the highest mean potassium deficit was 176 mmol on day 9, after which some potassium was regained; in the low-sodium group the highest deficit was 276 mmol on day 13. The normal-sodium group showed an immediate but temporary rise of the renin and aldosterone levels; in the low-sodium group renin and aldosterone increased more slowly but remained elevated. It is concluded that dietary sodium restriction increases diuretic-induced potassium loss, presumably by an increased activity of the renin-angiotensin-aldosterone system, while sodium delivery to the distal renal tubules remains sufficiently high to allow increased potassium secretion.
28952	8	17	potassium	Chemical	D011188
28952	27	39	hypokalaemia	Disease	D007008
28952	47	61	chlorthalidone	Chemical	D002752
28952	104	116	hypertension	Disease	D006973
28952	143	149	sodium	Chemical	D012964
28952	190	199	potassium	Chemical	D011188
28952	224	236	hypokalaemia	Disease	D007008
28952	356	368	hypertension	Disease	D006973
28952	383	395	hypokalaemia	Disease	D007008
28952	433	447	Chlorthalidone	Chemical	D002752
28952	516	522	sodium	Chemical	D012964
28952	543	549	sodium	Chemical	D012964
28952	615	624	potassium	Chemical	D011188
28952	708	719	aldosterone	Chemical	D000450
28952	767	776	potassium	Chemical	D011188
28952	908	914	sodium	Chemical	D012964
28952	938	947	potassium	Chemical	D011188
28952	996	1005	potassium	Chemical	D011188
28952	1031	1037	sodium	Chemical	D012964
28952	1099	1105	sodium	Chemical	D012964
28952	1168	1179	aldosterone	Chemical	D000450
28952	1199	1205	sodium	Chemical	D012964
28952	1222	1233	aldosterone	Chemical	D000450
28952	1308	1314	sodium	Chemical	D012964
28952	1354	1363	potassium	Chemical	D011188
28952	1419	1430	angiotensin	Chemical	D000809
28952	1431	1442	aldosterone	Chemical	D000450
28952	1457	1463	sodium	Chemical	D012964
28952	1546	1555	potassium	Chemical	D011188
28952	CID	D002752	D007008

19893084|t|Dynamic response of blood vessel in acute renal failure.
19893084|a|In this study we postulated that during acute renal failure induced by gentamicin the transient or dynamic response of blood vessels could be affected, and that antioxidants can prevent the changes in dynamic responses of blood vessels. The new approach to ex vivo blood vessel experiments in which not only the end points of vessels response within the time interval is considered, but also dynamics of this response, was used in this paper. Our results confirm the alteration in dynamic response of blood vessels during the change of pressure in gentamicin-treated animals. The beneficial effects of vitamin C administration to gentamicin-treated animals are also confirmed through: lower level of blood urea and creatinine and higher level of potassium. The pressure dynamic responses of isolated blood vessels show a faster pressure change in gentamicin-treated animals (8.07 +/- 1.7 s vs. 5.64 +/- 0.18 s). Vitamin C administration induced slowdown of pressure change back to the control values. The pressure dynamic properties, quantitatively defined by comparative pressure dynamic and total pressure dynamic, confirm the alteration in dynamic response of blood vessels during the change of pressure in gentamicin-treated animals and beneficial effects of vitamin C administration.
19893084	36	55	acute renal failure	Disease	D058186
19893084	97	116	acute renal failure	Disease	D058186
19893084	128	138	gentamicin	Chemical	D005839
19893084	605	615	gentamicin	Chemical	D005839
19893084	659	668	vitamin C	Chemical	D001205
19893084	687	697	gentamicin	Chemical	D005839
19893084	763	767	urea	Chemical	D014508
19893084	772	782	creatinine	Chemical	D003404
19893084	803	812	potassium	Chemical	D011188
19893084	904	914	gentamicin	Chemical	D005839
19893084	969	978	Vitamin C	Chemical	D001205
19893084	1267	1277	gentamicin	Chemical	D005839
19893084	1320	1329	vitamin C	Chemical	D001205
19893084	CID	D005839	D058186

18513945|t|The hemodynamics of oxytocin and other vasoactive agents during neuraxial anesthesia for cesarean delivery: findings in six cases.
18513945|a|Oxytocin is a commonly used uterotonic that can cause significant and even fatal hypotension, particularly when given as a bolus. The resulting hypotension can be produced by a decrease in systemic vascular resistance or cardiac output through a decrease in venous return. Parturients with normal volume status, heart valves and pulmonary vasculature most often respond to this hypotension with a compensatory increase in heart rate and stroke volume. Oxytocin-induced hypotension at cesarean delivery may be incorrectly attributed to blood loss. Pulse power analysis (also called "pulse contour analysis") of an arterial pressure wave form allows continuous evaluation of systemic vascular resistance and cardiac output in real time, thereby elucidating the causative factors behind changes in blood pressure. Pulse power analysis was conducted in six cases of cesarean delivery performed under neuraxial anesthesia. Hypotension in response to oxytocin was associated with a decrease in systemic vascular resistance and a compensatory increase in stroke volume, heart rate and cardiac output. Pulse power analysis may be helpful in determining the etiology of and treating hypotension during cesarean delivery under neuraxial anesthesia.
18513945	20	28	oxytocin	Chemical	D010121
18513945	131	139	Oxytocin	Chemical	D010121
18513945	212	223	hypotension	Disease	D007022
18513945	275	286	hypotension	Disease	D007022
18513945	509	520	hypotension	Disease	D007022
18513945	568	574	stroke	Disease	D020521
18513945	583	591	Oxytocin	Chemical	D010121
18513945	600	611	hypotension	Disease	D007022
18513945	666	676	blood loss	Disease	D006473
18513945	1049	1060	Hypotension	Disease	D007022
18513945	1076	1084	oxytocin	Chemical	D010121
18513945	1179	1185	stroke	Disease	D020521
18513945	1305	1316	hypotension	Disease	D007022
18513945	CID	D010121	D007022

18483878|t|Exaggerated expression of inflammatory mediators in vasoactive intestinal polypeptide knockout (VIP-/-) mice with cyclophosphamide (CYP)-induced cystitis.
18483878|a|Vasoactive intestinal polypeptide (VIP) is an immunomodulatory neuropeptide distributed in micturition pathways. VIP(-/-) mice exhibit altered bladder function and neurochemical properties in micturition pathways after cyclophosphamide (CYP)-induced cystitis. Given VIP's role as an anti-inflammatory mediator, we hypothesized that VIP(-/-) mice would exhibit enhanced inflammatory mediator expression after cystitis. A mouse inflammatory cytokine and receptor RT2 profiler array was used to determine regulated transcripts in the urinary bladder of wild type (WT) and VIP(-/-) mice with or without CYP-induced cystitis (150 mg/kg; i.p.; 48 h). Four binary comparisons were made: WT control versus CYP treatment (48 h), VIP(-/-) control versus CYP treatment (48 h), WT control versus VIP(-/-) control, and WT with CYP treatment (48 h) versus VIP(-/-) with CYP treatment (48 h). The genes presented represent (1) greater than 1.5-fold change in either direction and (2) the p value is less than 0.05 for the comparison being made. Several regulated genes were validated using enzyme-linked immunoassays including IL-1beta and CXCL1. CYP treatment significantly (p < or = 0.001) increased expression of CXCL1 and IL-1beta in the urinary bladder of WT and VIP(-/-) mice, but expression in VIP(-/-) mice with CYP treatment was significantly (p < or = 0.001) greater (4.2- to 13-fold increase) than that observed in WT urinary bladder (3.6- to 5-fold increase). The data suggest that in VIP(-/-) mice with bladder inflammation, inflammatory mediators are increased above that observed in WT with CYP. This shift in balance may contribute to increased bladder dysfunction in VIP(-/-) mice with bladder inflammation and altered neurochemical expression in micturition pathways.
18483878	114	130	cyclophosphamide	Chemical	D003520
18483878	132	135	CYP	Chemical	D003520
18483878	145	153	cystitis	Disease	D003556
18483878	374	390	cyclophosphamide	Chemical	D003520
18483878	392	395	CYP	Chemical	D003520
18483878	405	413	cystitis	Disease	D003556
18483878	563	571	cystitis	Disease	D003556
18483878	754	757	CYP	Chemical	D003520
18483878	766	774	cystitis	Disease	D003556
18483878	853	856	CYP	Chemical	D003520
18483878	899	902	CYP	Chemical	D003520
18483878	969	972	CYP	Chemical	D003520
18483878	1011	1014	CYP	Chemical	D003520
18483878	1287	1290	CYP	Chemical	D003520
18483878	1460	1463	CYP	Chemical	D003520
18483878	1656	1676	bladder inflammation	Disease	D001745
18483878	1746	1749	CYP	Chemical	D003520
18483878	1801	1820	bladder dysfunction	Disease	D001745
18483878	1843	1863	bladder inflammation	Disease	D001745
18483878	CID	D003520	D003556

17923537|t|Intraocular pressure in patients with uveitis treated with fluocinolone acetonide implants.
17923537|a|OBJECTIVE: To report the incidence and management of elevated intraocular pressure (IOP) in patients with uveitis treated with the fluocinolone acetonide (FA) intravitreal implant. DESIGN: Pooled data from 3 multicenter, double-masked, randomized, controlled, phase 2b/3 clinical trials evaluating the safety and efficacy of the 0.59-mg or 2.1-mg FA intravitreal implant or standard therapy were analyzed. RESULTS: During the 3-year follow-up, 71.0% of implanted eyes had an IOP increase of 10 mm Hg or more than baseline and 55.1%, 24.7%, and 6.2% of eyes reached an IOP of 30 mm Hg or more, 40 mm Hg or more, and 50 mm Hg or more, respectively. Topical IOP-lowering medication was administered in 74.8% of implanted eyes, and IOP-lowering surgeries, most of which were trabeculectomies (76.2%), were performed on 36.6% of implanted eyes. Intraocular pressure-lowering surgeries were considered a success (postoperative IOP of 6-21 mm Hg with or without additional IOP-lowering medication) in 85.1% of eyes at 1 year. The rate of hypotony (IOP </= 5 mm Hg) following IOP-lowering surgery (42.5%) was not different from that of implanted eyes not subjected to surgery (35.4%) (P = .09). CONCLUSION: Elevated IOP is a significant complication with the FA intravitreal implant but may be controlled with medication and surgery.
17923537	38	45	uveitis	Disease	D014605
17923537	59	81	fluocinolone acetonide	Chemical	D005446
17923537	145	174	elevated intraocular pressure	Disease	D009798
17923537	198	205	uveitis	Disease	D014605
17923537	223	245	fluocinolone acetonide	Chemical	D005446
17923537	247	249	FA	Chemical	D005446
17923537	439	441	FA	Chemical	D005446
17923537	1123	1131	hypotony	Disease	D015814
17923537	CID	D005446	D009798

15096016|t|Pallidal stimulation: an alternative to pallidotomy?
15096016|a|A resurgence of interest in the surgical treatment of Parkinson's disease (PD) came with the rediscovery of posteroventral pallidotomy by Laitinen in 1985. Laitinen's procedure improved most symptoms in drug-resistant PD, which engendered wide interest in the neurosurgical community. Another lesioning procedure, ventrolateral thalamotomy, has become a powerful alternative to stimulate the nucleus ventralis intermedius, producing high long-term success rates and low morbidity rates. Pallidal stimulation has not met with the same success. According to the literature pallidotomy improves the "on" symptoms of PD, such as dyskinesias, as well as the "off" symptoms, such as rigidity, bradykinesia, and on-off fluctuations. Pallidal stimulation improves bradykinesia and rigidity to a minor extent; however, its strength seems to be in improving levodopa-induced dyskinesias. Stimulation often produces an improvement in the hyper- or dyskinetic upper limbs, but increases the "freezing" phenomenon in the lower limbs at the same time. Considering the small increase in the patient's independence, the high costs of bilateral implants, and the difficulty most patients experience in handling the devices, the question arises as to whether bilateral pallidal stimulation is a real alternative to pallidotomy.
15096016	107	126	Parkinson's disease	Disease	D010300
15096016	128	130	PD	Disease	D010300
15096016	271	273	PD	Disease	D010300
15096016	666	668	PD	Disease	D010300
15096016	678	689	dyskinesias	Disease	D004409
15096016	730	738	rigidity	Disease	D009127
15096016	740	752	bradykinesia	Disease	D018476
15096016	809	821	bradykinesia	Disease	D018476
15096016	826	834	rigidity	Disease	D009127
15096016	901	909	levodopa	Chemical	D007980
15096016	918	929	dyskinesias	Disease	D004409
15096016	980	1000	hyper- or dyskinetic	Disease	D006948|D004409
15096016	CID	D007980	D004409

12734532|t|Case report: Dexatrim (Phenylpropanolamine) as a cause of myocardial infarction.
12734532|a|Phenylpropanolamine (PPA) is a sympathetic amine used in over-the-counter cold remedies and weight-control preparations worldwide. Its use has been associated with hypertensive episodes and hemorrhagic strokes in younger women. Several reports have linked the abuse of PPA with myocardial injury, especially when overdose is involved. We report here the first case of Dexatrim (PPA)-induced myocardial injury in a young woman who was using it at recommended doses for weight control. In addition, we review the 7 other cases of PPA related myocardial injury that have been reported so far. Physicians and patients should be alert to the potential cardiac risk associated with the use of PPA, even at doses generally considered to be safe.
12734532	13	21	Dexatrim	Chemical	D010665
12734532	23	42	Phenylpropanolamine	Chemical	D010665
12734532	58	79	myocardial infarction	Disease	D009203
12734532	81	100	Phenylpropanolamine	Chemical	D010665
12734532	102	105	PPA	Chemical	D010665
12734532	124	129	amine	Chemical	D000588
12734532	245	257	hypertensive	Disease	D006973
12734532	271	290	hemorrhagic strokes	Disease	D006470|D020521	hemorrhagic|strokes
12734532	350	353	PPA	Chemical	D010665
12734532	359	376	myocardial injury	Disease	D009202
12734532	394	402	overdose	Disease	D062787
12734532	449	457	Dexatrim	Chemical	D010665
12734532	459	462	PPA	Chemical	D010665
12734532	472	489	myocardial injury	Disease	D009202
12734532	609	612	PPA	Chemical	D010665
12734532	621	638	myocardial injury	Disease	D009202
12734532	768	771	PPA	Chemical	D010665
12734532	CID	D010665	D009203

12013711|t|Risperidone-associated, benign transient visual disturbances in schizophrenic patients with a past history of LSD abuse.
12013711|a|Two schizophrenic patients, who had a prior history of LSD abuse and who had previously developed EPS with classic antipsychotics, were successfully treated with risperidone. They both reported short episodes of transient visual disturbances, which appeared immediately after starting treatment with risperidone. This imagery resembled visual disturbances previously experienced as "flashbacks" related to prior LSD consumption. Risperidone administration was continued and the visual disturbances gradually wore off. During a six-month follow-up period, there was no recurrence of visual disturbances. This phenomenon may be interpreted as a benign, short-term and self-limiting side effect which does not contraindicate the use of risperidone or interfere with treatment. Conclusions based on two case reports should be taken with appropriate caution.
12013711	0	11	Risperidone	Chemical	D018967
12013711	41	60	visual disturbances	Disease	D010468
12013711	64	77	schizophrenic	Disease	D012559
12013711	110	113	LSD	Chemical	D008238
12013711	125	138	schizophrenic	Disease	D012559
12013711	176	179	LSD	Chemical	D008238
12013711	219	222	EPS	Disease	D001480
12013711	283	294	risperidone	Chemical	D018967
12013711	343	362	visual disturbances	Disease	D010468
12013711	421	432	risperidone	Chemical	D018967
12013711	457	476	visual disturbances	Disease	D010468
12013711	533	536	LSD	Chemical	D008238
12013711	550	561	Risperidone	Chemical	D018967
12013711	599	618	visual disturbances	Disease	D010468
12013711	703	722	visual disturbances	Disease	D010468
12013711	854	865	risperidone	Chemical	D018967
12013711	CID	D018967	D010468

11861791|t|Activation of poly(ADP-ribose) polymerase contributes to development of doxorubicin-induced heart failure.
11861791|a|Activation of the nuclear enzyme poly(ADP-ribose) polymerase (PARP) by oxidant-mediated DNA damage is an important pathway of cell dysfunction and tissue injury in conditions associated with oxidative stress. Increased oxidative stress is a major factor implicated in the cardiotoxicity of doxorubicin (DOX), a widely used antitumor anthracycline antibiotic. Thus, we hypothesized that the activation of PARP may contribute to the DOX-induced cardiotoxicity. Using a dual approach of PARP-1 suppression, by genetic deletion or pharmacological inhibition with the phenanthridinone PARP inhibitor PJ34, we now demonstrate the role of PARP in the development of cardiac dysfunction induced by DOX. PARP-1+/+ and PARP-1-/- mice received a single injection of DOX (25 mg/kg i.p). Five days after DOX administration, left ventricular performance was significantly depressed in PARP-1+/+ mice, but only to a smaller extent in PARP-1-/- ones. Similar experiments were conducted in BALB/c mice treated with PJ34 or vehicle. Treatment with a PJ34 significantly improved cardiac dysfunction and increased the survival of the animals. In addition PJ34 significantly reduced the DOX-induced increase in the serum lactate dehydrogenase and creatine kinase activities but not metalloproteinase activation in the heart. Thus, PARP activation contributes to the cardiotoxicity of DOX. PARP inhibitors may exert protective effects against the development of severe cardiac complications associated with the DOX treatment.
11861791	14	30	poly(ADP-ribose)	Chemical	D011064
11861791	72	83	doxorubicin	Chemical	D004317
11861791	92	105	heart failure	Disease	D006333
11861791	140	156	poly(ADP-ribose)	Chemical	D011064
11861791	379	393	cardiotoxicity	Disease	D066126
11861791	397	408	doxorubicin	Chemical	D004317
11861791	410	413	DOX	Chemical	D004317
11861791	440	453	anthracycline	Chemical	D018943
11861791	538	541	DOX	Chemical	D004317
11861791	550	564	cardiotoxicity	Disease	D066126
11861791	702	706	PJ34	Chemical	C434926
11861791	766	785	cardiac dysfunction	Disease	D006331
11861791	797	800	DOX	Chemical	D004317
11861791	862	865	DOX	Chemical	D004317
11861791	898	901	DOX	Chemical	D004317
11861791	1105	1109	PJ34	Chemical	C434926
11861791	1139	1143	PJ34	Chemical	C434926
11861791	1167	1186	cardiac dysfunction	Disease	D006331
11861791	1242	1246	PJ34	Chemical	C434926
11861791	1273	1276	DOX	Chemical	D004317
11861791	1307	1314	lactate	Chemical	D019344
11861791	1333	1341	creatine	Chemical	D003401
11861791	1452	1466	cardiotoxicity	Disease	D066126
11861791	1470	1473	DOX	Chemical	D004317
11861791	1554	1575	cardiac complications	Disease	D005117
11861791	1596	1599	DOX	Chemical	D004317
11861791	CID	D004317	D006333

11302406|t|Fluconazole-induced torsade de pointes.
11302406|a|OBJECTIVE: To present a case of fluconazole-associated torsade de pointes (TDP) and discuss fluconazole's role in causing TDP. CASE SUMMARY: A 68-year-old white woman with Candida glabrata isolated from a presacral abscess developed TDP eight days after commencing oral fluconazole The patient had no other risk factors for TDP, including coronary artery disease, cardiomyopathy, congestive heart failure, and electrolyte abnormalities There was a temporal association between the initiation of fluconazole and TDP. The TDP resolved when fluconazole was discontinued; however, the patient continued to have premature ventricular contractions and nonsustained ventricular tachycardia (NSVT) until six days after drug cessation DISCUSSION: Use of the Naranjo probability scale indicates a probable relationship between the use of fluconazole and the development of TDP. The possible mechanism is depression of rapidly activating delayed rectifier potassium currents. In our patient, there was no other etiology identified that could explain QT prolongation or TDP The complete disappearance of NSVT and premature ventricular contractions followed by normalization of QT interval after the drug was stopped strongly suggests fluconazole as the etiology. CONCLUSIONS: Clinicians should be aware that fluconazole, even at low doses, may cause prolongation of the QT interval, leading to TDP. Serial electrocardiographic monitoring may be considered when fluconazole is administered in patients who are at risk for ventricular arrhythmias.
11302406	0	11	Fluconazole	Chemical	D015725
11302406	20	38	torsade de pointes	Disease	D016171
11302406	72	83	fluconazole	Chemical	D015725
11302406	95	113	torsade de pointes	Disease	D016171
11302406	115	118	TDP	Disease	D016171
11302406	132	143	fluconazole	Chemical	D015725
11302406	162	165	TDP	Disease	D016171
11302406	273	276	TDP	Disease	D016171
11302406	310	321	fluconazole	Chemical	D015725
11302406	364	367	TDP	Disease	D016171
11302406	379	402	coronary artery disease	Disease	D003324
11302406	404	418	cardiomyopathy	Disease	D009202
11302406	420	444	congestive heart failure	Disease	D006333
11302406	535	546	fluconazole	Chemical	D015725
11302406	551	554	TDP	Disease	D016171
11302406	560	563	TDP	Disease	D016171
11302406	578	589	fluconazole	Chemical	D015725
11302406	647	681	premature ventricular contractions	Disease	D018879
11302406	699	722	ventricular tachycardia	Disease	D017180
11302406	724	728	NSVT	Disease	D017180
11302406	868	879	fluconazole	Chemical	D015725
11302406	903	906	TDP	Disease	D016171
11302406	934	944	depression	Disease	D003866
11302406	985	994	potassium	Chemical	D011188
11302406	1079	1094	QT prolongation	Disease	D008133
11302406	1098	1101	TDP	Disease	D016171
11302406	1132	1136	NSVT	Disease	D017180
11302406	1141	1175	premature ventricular contractions	Disease	D018879
11302406	1262	1273	fluconazole	Chemical	D015725
11302406	1336	1347	fluconazole	Chemical	D015725
11302406	1378	1409	prolongation of the QT interval	Disease	D008133
11302406	1422	1425	TDP	Disease	D016171
11302406	1489	1500	fluconazole	Chemical	D015725
11302406	1549	1572	ventricular arrhythmias	Disease	D001145
11302406	CID	D015725	D016171

11058428|t|High-dose methylprednisolone may do more harm for spinal cord injury.
11058428|a|Because of the National Acute Spinal Cord Injury Studies (NASCIS), high-dose methylprednisolone became the standard of care for the acute spinal cord injury. In the NASCIS, there was no mention regarding the possibility of acute corticosteroid myopathy that high-dose methylprednisolone may cause. The dosage of methylprednisolone recommended by the NASCIS 3 is the highest dose of steroids ever being used during a 2-day period for any clinical condition. We hypothesize that it may cause some damage to the muscle of spinal cord injury patients. Further, steroid myopathy recovers naturally and the neurological improvement shown in the NASCIS may be just a recording of this natural motor recovery from the steroid myopathy, instead of any protection that methylprednisolone offers to the spinal cord injury. To our knowledge, this is the first discussion considering the possibility that the methylprednisolone recommended by NASCIS may cause acute corticosteroid myopathy.
11058428	10	28	methylprednisolone	Chemical	D008775
11058428	50	68	spinal cord injury	Disease	D013119
11058428	100	118	Spinal Cord Injury	Disease	D013119
11058428	147	165	methylprednisolone	Chemical	D008775
11058428	208	226	spinal cord injury	Disease	D013119
11058428	299	313	corticosteroid	Chemical	D000305
11058428	314	322	myopathy	Disease	D009135
11058428	338	356	methylprednisolone	Chemical	D008775
11058428	382	400	methylprednisolone	Chemical	D008775
11058428	452	460	steroids	Chemical	D013256
11058428	565	585	damage to the muscle	Disease	D009135
11058428	589	607	spinal cord injury	Disease	D013119
11058428	627	634	steroid	Chemical	D013256
11058428	635	643	myopathy	Disease	D009135
11058428	780	787	steroid	Chemical	D013256
11058428	788	796	myopathy	Disease	D009135
11058428	829	847	methylprednisolone	Chemical	D008775
11058428	862	880	spinal cord injury	Disease	D013119
11058428	966	984	methylprednisolone	Chemical	D008775
11058428	1023	1037	corticosteroid	Chemical	D000305
11058428	1038	1046	myopathy	Disease	D009135
11058428	CID	D008775	D009135

11022397|t|Probing peripheral and central cholinergic system responses.
11022397|a|OBJECTIVE: The pharmacological response to drugs that act on the cholinergic system of the iris has been used to predict deficits in central cholinergic functioning due to diseases such as Alzheimer's disease, yet correlations between central and peripheral responses have not been properly studied. This study assessed the effect of normal aging on (1) the tropicamide-induced increase in pupil diameter, and (2) the reversal of this effect with pilocarpine. Scopolamine was used as a positive control to detect age-dependent changes in central cholinergic functioning in the elderly. DESIGN: Randomized double-blind controlled trial. PARTICIPANTS: Ten healthy elderly (mean age 70) and 9 young (mean age 33) volunteers. INTERVENTIONS: Pupil diameter was monitored using a computerized infrared pupillometer over 4 hours. The study involved 4 sessions. In 1 session, tropicamide (20 microL, 0.01%) was administered to one eye and placebo to the other. In another session, tropicamide (20 microL, 0.01%) was administered to both eyes, followed 23 minutes later by the application of pilocarpine (20 microL, 0.1%) to one eye and placebo to the other. All eye drops were given in a randomized order. In 2 separate sessions, a single dose of scopolamine (0.5 mg, intravenously) or placebo was administered, and the effects on word recall were measured using the Buschke Selective Reminding Test over 2 hours. OUTCOME MEASURES: Pupil size at time points after administration of tropicamide and pilocarpine; scopolamine-induced impairment in word recall. RESULTS: There was no significant difference between elderly and young volunteers in pupillary response to tropicamide at any time point (p > 0.05). The elderly group had a significantly greater pilocarpine-induced net decrease in pupil size 85, 125, 165 and 215 minutes after administration, compared with the young group (p < 0.05). Compared with the young group, the elderly group had greater scopolamine-induced impairment in word recall 60, 90 and 120 minutes after administration (p < 0.05). CONCLUSION: There is an age-related pupillary response to pilocarpine that is not found with tropicamide. Thus, pilocarpine may be useful to assess variations in central cholinergic function in elderly patients.
11022397	250	269	Alzheimer's disease	Disease	D000544
11022397	419	430	tropicamide	Chemical	D014331
11022397	508	519	pilocarpine	Chemical	D010862
11022397	521	532	Scopolamine	Chemical	D012601
11022397	929	940	tropicamide	Chemical	D014331
11022397	1034	1045	tropicamide	Chemical	D014331
11022397	1144	1155	pilocarpine	Chemical	D010862
11022397	1300	1311	scopolamine	Chemical	D012601
11022397	1535	1546	tropicamide	Chemical	D014331
11022397	1551	1562	pilocarpine	Chemical	D010862
11022397	1564	1575	scopolamine	Chemical	D012601
11022397	1584	1609	impairment in word recall	Disease	D008569
11022397	1718	1729	tropicamide	Chemical	D014331
11022397	1806	1817	pilocarpine	Chemical	D010862
11022397	2007	2018	scopolamine	Chemical	D012601
11022397	2027	2052	impairment in word recall	Disease	D008569
11022397	2167	2178	pilocarpine	Chemical	D010862
11022397	2202	2213	tropicamide	Chemical	D014331
11022397	2221	2232	pilocarpine	Chemical	D010862
11022397	CID	D012601	D008569

10692744|t|Acetazolamide-induced Gerstmann syndrome.
10692744|a|Acute confusion induced by acetazolamide is a well known adverse drug reaction in patients with renal impairment. We report a case of acetazolamide-induced Gerstmann syndrome in a patient with normal renal function, to highlight predisposing factors that are frequently overlooked.
10692744	0	13	Acetazolamide	Chemical	D000086
10692744	22	40	Gerstmann syndrome	Disease	D005862
10692744	48	57	confusion	Disease	D003221
10692744	69	82	acetazolamide	Chemical	D000086
10692744	138	154	renal impairment	Disease	D007674
10692744	176	189	acetazolamide	Chemical	D000086
10692744	198	216	Gerstmann syndrome	Disease	D005862
10692744	CID	D000086	D005862

10565806|t|Hypomania-like syndrome induced by olanzapine.
10565806|a|We report a female patient with a diagnosis of a not otherwise specified psychotic disorder (DSM-IV) who developed hypomania shortly after the introduction of olanzapine treatment.
10565806	0	9	Hypomania	Disease	D001714
10565806	35	45	olanzapine	Chemical	C076029
10565806	120	138	psychotic disorder	Disease	D011618
10565806	162	171	hypomania	Disease	D001714
10565806	206	216	olanzapine	Chemical	C076029
10565806	CID	C076029	D001714

9061311|t|Neutrophil superoxide and hydrogen peroxide production in patients with acute liver failure.
9061311|a|Defects in superoxide and hydrogen peroxide production may be implicated in the high incidence of bacterial infections in patients with acute liver failure (ALF). In the present study, oxygen radical production in patients with ALF due to paracetamol overdose was compared with that of healthy volunteers. Neutrophils from 14 ALF patients were stimulated via the complement receptors using zymosan opsonized with ALF or control serum. Superoxide and hydrogen peroxide production by ALF neutrophils stimulated with zymosan opsonized with ALF serum was significantly reduced compared with the control subjects (P < 0.01). This defect persisted when zymosan opsonized by control serum was used (P < 0.05). Superoxide and hydrogen peroxide production in neutrophils stimulated with formyl-methionyl-leucyl-phenylalanine (fMLP) from a further 18 ALF patients was unaffected compared with control neutrophils. Serum C3 complement levels were significantly reduced in ALF patients compared with control subjects (P < 0.0005). These results demonstrate a neutrophil defect in ALF due to paracetamol overdose, that is complement dependent but independent of serum complement, possibly connected to the complement receptor.
9061311	11	21	superoxide	Chemical	D013481
9061311	26	43	hydrogen peroxide	Chemical	D006861
9061311	72	91	acute liver failure	Disease	D017114
9061311	104	114	superoxide	Chemical	D013481
9061311	119	136	hydrogen peroxide	Chemical	D006861
9061311	191	211	bacterial infections	Disease	D001424
9061311	229	248	acute liver failure	Disease	D017114
9061311	250	253	ALF	Disease	D017114
9061311	278	284	oxygen	Chemical	D010100
9061311	321	324	ALF	Disease	D017114
9061311	332	343	paracetamol	Chemical	D000082
9061311	344	352	overdose	Disease	D062787
9061311	419	422	ALF	Disease	D017114
9061311	506	509	ALF	Disease	D017114
9061311	528	538	Superoxide	Chemical	D013481
9061311	543	560	hydrogen peroxide	Chemical	D006861
9061311	575	578	ALF	Disease	D017114
9061311	630	633	ALF	Disease	D017114
9061311	796	806	Superoxide	Chemical	D013481
9061311	811	828	hydrogen peroxide	Chemical	D006861
9061311	871	908	formyl-methionyl-leucyl-phenylalanine	Chemical	D009240
9061311	910	914	fMLP	Chemical	D009240
9061311	934	937	ALF	Disease	D017114
9061311	1054	1057	ALF	Disease	D017114
9061311	1161	1164	ALF	Disease	D017114
9061311	1172	1183	paracetamol	Chemical	D000082
9061311	1184	1192	overdose	Disease	D062787
9061311	CID	D000082	D017114

8617710|t|Absence of effect of sertraline on time-based sensitization of cognitive impairment with haloperidol.
8617710|a|This double-blind, randomized, placebo-controlled study evaluated the effects of haloperidol alone and haloperidol plus sertraline on cognitive and psychomotor function in 24 healthy male subjects. METHOD: All subjects received placebo on Day 1 and haloperidol 2 mg on Days 2 and 25. From Days 9 to 25, subjects were randomly assigned to either sertraline (12 subjects) or placebo (12 subjects); the sertraline dose was titrated from 50 to 200 mg/day from Days 9 to 16, and remained at 200 mg/day for the final 10 days of the drug administration period. Cognitive function testing was performed before dosing and over a 24-hour period after dosing on Days 1, 2, and 25. RESULTS: Impairment of cognitive function was observed 6 to 8 hours after administration of haloperidol on Day 2 but was not evident 23 hours after dosing. When single-dose haloperidol was given again 25 days later, greater impairment with earlier onset was noted in several tests in both treatment groups, suggesting enhancement of this effect. There was no indication that sertraline exacerbated the impairment produced by haloperidol since an equivalent effect also occurred in the placebo group. Three subjects (2 on sertraline and 1 on placebo) withdrew from the study because of side effects. Ten subjects in each group reported side effects related to treatment. The side effect profiles of sertraline and of placebo were similar. CONCLUSION: Haloperidol produced a clear profile of cognitive impairment that was not worsened by concomitant sertraline administration.
8617710	21	31	sertraline	Chemical	D020280
8617710	63	83	cognitive impairment	Disease	D003072
8617710	89	100	haloperidol	Chemical	D006220
8617710	183	194	haloperidol	Chemical	D006220
8617710	205	216	haloperidol	Chemical	D006220
8617710	222	232	sertraline	Chemical	D020280
8617710	351	362	haloperidol	Chemical	D006220
8617710	447	457	sertraline	Chemical	D020280
8617710	502	512	sertraline	Chemical	D020280
8617710	781	813	Impairment of cognitive function	Disease	D003072
8617710	864	875	haloperidol	Chemical	D006220
8617710	945	956	haloperidol	Chemical	D006220
8617710	1147	1157	sertraline	Chemical	D020280
8617710	1197	1208	haloperidol	Chemical	D006220
8617710	1293	1303	sertraline	Chemical	D020280
8617710	1470	1480	sertraline	Chemical	D020280
8617710	1522	1533	Haloperidol	Chemical	D006220
8617710	1562	1582	cognitive impairment	Disease	D003072
8617710	1620	1630	sertraline	Chemical	D020280
8617710	CID	D006220	D003072

8494478|t|Ciprofloxacin-induced nephrotoxicity in patients with cancer.
8494478|a|Nephrotoxicity associated with ciprofloxacin is uncommon. Five patients with cancer who developed acute renal failure that followed treatment with ciprofloxacin are described and an additional 15 cases reported in the literature are reviewed. Other than elevation of serum creatinine levels, characteristic clinical manifestations and abnormal laboratory findings are not frequently present. Allergic interstitial nephritis is believed to be the underlying pathological-process. Definitive diagnosis requires performance of renal biopsy, although this is not always feasible. An improvement in renal function that followed the discontinuation of the offending antibiotic supports the presumptive diagnosis of ciprofloxacin-induced acute renal failure.
8494478	0	13	Ciprofloxacin	Chemical	D002939
8494478	22	36	nephrotoxicity	Disease	D007674
8494478	54	60	cancer	Disease	D009369
8494478	62	76	Nephrotoxicity	Disease	D007674
8494478	93	106	ciprofloxacin	Chemical	D002939
8494478	139	145	cancer	Disease	D009369
8494478	160	179	acute renal failure	Disease	D058186
8494478	209	222	ciprofloxacin	Chemical	D002939
8494478	335	345	creatinine	Chemical	D003404
8494478	463	485	interstitial nephritis	Disease	D009395
8494478	771	784	ciprofloxacin	Chemical	D002939
8494478	793	812	acute renal failure	Disease	D058186
8494478	CID	D002939	D058186

8475949|t|Case report: pentamidine and polymorphic ventricular tachycardia revisited.
8475949|a|Pentamidine isethionate has been associated with ventricular tachyarrhythmias, including torsade de pointes. This article reports two cases of this complication and reviews all reported cases to date. Pentamidine-induced torsade de pointes may be related to serum magnesium levels and hypomagnesemia may synergistically induce torsade. Torsade de pointes occurred after an average of 10 days of treatment with pentamidine. In these patients, no other acute side effects of pentamidine were observed. Torsade de pointes can be treated when recognized early, possibly without discontinuation of pentamidine. When QTc interval prolongation is observed, early magnesium supplementation is advocated.
8475949	13	24	pentamidine	Chemical	D010419
8475949	41	64	ventricular tachycardia	Disease	D017180
8475949	76	99	Pentamidine isethionate	Chemical	D010419
8475949	125	153	ventricular tachyarrhythmias	Disease	D017180
8475949	165	183	torsade de pointes	Disease	D016171
8475949	277	288	Pentamidine	Chemical	D010419
8475949	297	315	torsade de pointes	Disease	D016171
8475949	340	349	magnesium	Chemical	D008274
8475949	361	375	hypomagnesemia	Disease	C537153
8475949	412	430	Torsade de pointes	Disease	D016171
8475949	486	497	pentamidine	Chemical	D010419
8475949	549	560	pentamidine	Chemical	D010419
8475949	576	594	Torsade de pointes	Disease	D016171
8475949	669	680	pentamidine	Chemical	D010419
8475949	687	712	QTc interval prolongation	Disease	D008133
8475949	732	741	magnesium	Chemical	D008274
8475949	CID	D010419	D016171

7710775|t|Time dependence of plasma malondialdehyde, oxypurines, and nucleosides during incomplete cerebral ischemia in the rat.
7710775|a|Incomplete cerebral ischemia (30 min) was induced in the rat by bilaterally clamping the common carotid arteries. Peripheral venous blood samples were withdrawn from the femoral vein four times (once every 5 min) before ischemia (0 time) and 5, 15, and 30 min after ischemia. Plasma extracts were analyzed by a highly sensitive high-performance liquid chromatographic method for the direct determination of malondialdehyde, oxypurines, and nucleosides. During ischemia, a time-dependent increase of plasma oxypurines and nucleosides was observed. Plasma malondialdehyde, which was present in minimal amount at zero time (0.058 mumol/liter plasma; SD 0.015), increased after 5 min of ischemia, resulting in a fivefold increase after 30 min of carotid occlusion (0.298 mumol/liter plasma; SD 0.078). Increased plasma malondialdehyde was also recorded in two other groups of animals subjected to the same experimental model, one receiving 20 mg/kg b.w. of the cyclooxygenase inhibitor acetylsalicylate intravenously immediately before ischemia, the other receiving 650 micrograms/kg b.w. of the hypotensive drug nitroprusside at a flow rate of 103 microliters/min intravenously during ischemia, although in this latter group malondialdehyde was significantly higher. The present data indicate that the determination of malondialdehyde, oxypurines, and nucleosides in peripheral blood, may be used to monitor the metabolic alterations of tissues occurring during ischemic phenomena.(ABSTRACT TRUNCATED AT 250 WORDS)
7710775	26	41	malondialdehyde	Chemical	D008315
7710775	43	53	oxypurines	Chemical	-1
7710775	59	70	nucleosides	Chemical	D009705
7710775	89	106	cerebral ischemia	Disease	D002545
7710775	130	147	cerebral ischemia	Disease	D002545
7710775	339	347	ischemia	Disease	D007511
7710775	385	393	ischemia	Disease	D007511
7710775	526	541	malondialdehyde	Chemical	D008315
7710775	543	553	oxypurines	Chemical	-1
7710775	559	570	nucleosides	Chemical	D009705
7710775	579	587	ischemia	Disease	D007511
7710775	625	635	oxypurines	Chemical	-1
7710775	640	651	nucleosides	Chemical	D009705
7710775	673	688	malondialdehyde	Chemical	D008315
7710775	802	810	ischemia	Disease	D007511
7710775	934	949	malondialdehyde	Chemical	D008315
7710775	1101	1117	acetylsalicylate	Chemical	D001241
7710775	1151	1159	ischemia	Disease	D007511
7710775	1211	1222	hypotensive	Disease	D007022
7710775	1228	1241	nitroprusside	Chemical	D009599
7710775	1301	1309	ischemia	Disease	D007511
7710775	1341	1356	malondialdehyde	Chemical	D008315
7710775	1435	1450	malondialdehyde	Chemical	D008315
7710775	1452	1462	oxypurines	Chemical	-1
7710775	1468	1479	nucleosides	Chemical	D009705
7710775	1578	1586	ischemic	Disease	D007511
7710775	CID	D008315	D002545

7650771|t|Cholinergic toxicity resulting from ocular instillation of echothiophate iodide eye drops.
7650771|a|A patient developed a severe cholinergic syndrome from the use of echothiophate iodide ophthalmic drops, presented with profound muscle weakness and was initially given the diagnosis of myasthenia gravis. Red blood cell and serum cholinesterase levels were severely depressed and symptoms resolved spontaneously following discontinuation of the eye drops.
7650771	12	20	toxicity	Disease	D064420
7650771	59	79	echothiophate iodide	Chemical	D004456
7650771	157	177	echothiophate iodide	Chemical	D004456
7650771	220	235	muscle weakness	Disease	D018908
7650771	277	294	myasthenia gravis	Disease	D009157
7650771	CID	D004456	D018908

7565311|t|Acute renal failure in high dose carboplatin chemotherapy.
7565311|a|Carboplatin has been reported to cause acute renal failure when administered in high doses to adult patients. We report a 4 1/2-year-old girl who was treated with high-dose carboplatin for metastatic parameningeal embryonal rhabdomyosarcoma. Acute renal failure developed followed by a slow partial recovery of renal function. Possible contributing factors are discussed.
7565311	0	19	Acute renal failure	Disease	D058186
7565311	33	44	carboplatin	Chemical	D016190
7565311	59	70	Carboplatin	Chemical	D016190
7565311	98	117	acute renal failure	Disease	D058186
7565311	232	243	carboplatin	Chemical	D016190
7565311	273	299	embryonal rhabdomyosarcoma	Disease	D018233
7565311	301	320	Acute renal failure	Disease	D058186
7565311	CID	D016190	D058186

7421734|t|Endometrial carcinoma after Hodgkin disease in childhood.
7421734|a|A 34-year-old patient developed metastic endometrial carcinoma after Hodgkin disease in childhood. She had ovarian failure after abdominal irradiation and chemotherapy for Hodgkin disease, and received exogenous estrogens, a treatment implicated in the development of endometrial cancer in menopausal women. Young women on replacement estrogens for ovarian failure after cancer therapy may also have increased risk of endometrial carcinoma and should be examined periodically.
7421734	0	21	Endometrial carcinoma	Disease	D016889
7421734	28	43	Hodgkin disease	Disease	D006689
7421734	99	120	endometrial carcinoma	Disease	D016889
7421734	127	142	Hodgkin disease	Disease	D006689
7421734	165	180	ovarian failure	Disease	D010049
7421734	230	245	Hodgkin disease	Disease	D006689
7421734	270	279	estrogens	Chemical	D004967
7421734	326	344	endometrial cancer	Disease	D016889
7421734	393	402	estrogens	Chemical	D004967
7421734	407	422	ovarian failure	Disease	D010049
7421734	429	435	cancer	Disease	D009369
7421734	476	497	endometrial carcinoma	Disease	D016889
7421734	CID	D004967	D016889

6732043|t|Induction of the obstructive sleep apnea syndrome in a woman by exogenous androgen administration.
6732043|a|We documented airway occlusion during sleep and an abnormally high supraglottic resistance while awake in a 54-yr-old woman who had developed physical changes and the syndrome of obstructive sleep apnea while being administered exogenous androgens. When the androgens were withdrawn, the patient's physical changes, symptoms, sleep study, and supraglottic resistance all returned to normal. A rechallenge with androgen produced symptoms of obstructive sleep apnea that abated upon withdrawal of the hormone. Previous reports have favored a role of androgens in the pathogenesis of sleep apnea. Our report provides direct evidence for this role. Structural and functional measurements indicate that androgens exert a permissive or necessary action on the structural configuration of the oropharynx that predisposes to obstruction during sleep. Development of the obstructive sleep apnea syndrome must be considered a possible side effect of androgen therapy.
6732043	17	49	obstructive sleep apnea syndrome	Disease	D020181
6732043	74	82	androgen	Chemical	D000728
6732043	266	301	syndrome of obstructive sleep apnea	Disease	D020181
6732043	337	346	androgens	Chemical	D000728
6732043	357	366	androgens	Chemical	D000728
6732043	509	517	androgen	Chemical	D000728
6732043	539	562	obstructive sleep apnea	Disease	D020181
6732043	647	656	androgens	Chemical	D000728
6732043	680	691	sleep apnea	Disease	D012891
6732043	797	806	androgens	Chemical	D000728
6732043	961	993	obstructive sleep apnea syndrome	Disease	D020181
6732043	1039	1047	androgen	Chemical	D000728
6732043	CID	D000728	D020181

6454943|t|Effect of captopril on pre-existing and aminonucleoside-induced proteinuria in spontaneously hypertensive rats.
6454943|a|Proteinuria is a side effect of captopril treatment in hypertensive patients. The possibility of reproducing the same renal abnormality with captopril was examined in SHR. Oral administration of captopril at 100 mg/kg for 14 days failed to aggravate proteinuria pre-existing in SHR. Also, captopril treatment failed to potentiate or facilitate development of massive proteinuria invoked by puromycin aminonucleoside in SHR. Captopril had little or no demonstrable effects on serum electrolyte concentrations, excretion of urine, sodium and potassium, endogenous creatinine clearance, body weight, and food and water consumption. However, ketone bodies were consistently present in urine and several lethalities occurred during multiple dosing of captopril in SHR.
6454943	10	19	captopril	Chemical	D002216
6454943	40	55	aminonucleoside	Chemical	D011692
6454943	64	75	proteinuria	Disease	D011507
6454943	93	105	hypertensive	Disease	D006973
6454943	112	123	Proteinuria	Disease	D011507
6454943	144	153	captopril	Chemical	D002216
6454943	167	179	hypertensive	Disease	D006973
6454943	230	247	renal abnormality	Disease	D007674
6454943	253	262	captopril	Chemical	D002216
6454943	307	316	captopril	Chemical	D002216
6454943	362	373	proteinuria	Disease	D011507
6454943	401	410	captopril	Chemical	D002216
6454943	479	490	proteinuria	Disease	D011507
6454943	502	527	puromycin aminonucleoside	Chemical	D011692
6454943	536	545	Captopril	Chemical	D002216
6454943	641	647	sodium	Chemical	D012964
6454943	652	661	potassium	Chemical	D011188
6454943	674	684	creatinine	Chemical	D003404
6454943	750	756	ketone	Chemical	D007659
6454943	858	867	captopril	Chemical	D002216
6454943	CID	D011692	D011507

6153967|t|Epileptogenic properties of enflurane and their clinical interpretation.
6153967|a|Three cases of EEG changes induced by single exposure to enflurane anesthesia are reported. In one patient, enflurane administered during a donor nephrectomy resulted in unexpected partial motor seizures. Until the cause of the seizures was correctly identified, the patient was inappropriately treated with anticonvulsants. Two other patients suffered from partial, complex and generalized seizures uncontrolled by medication. Epileptic foci delineated and activated by enflurane were surgically ablated and the patients are now seizure-free. Previous exposures to enflurane have to be disclosed to avoid mistakes in clinical interpretation of the EEG. On the other hand, enflurane may prove to be a safe fast acting activator of epileptic foci during corticography or depth electrode intraoperative recordings.
6153967	28	37	enflurane	Chemical	D004737
6153967	130	139	enflurane	Chemical	D004737
6153967	181	190	enflurane	Chemical	D004737
6153967	268	276	seizures	Disease	D012640
6153967	301	309	seizures	Disease	D012640
6153967	464	472	seizures	Disease	D012640
6153967	501	510	Epileptic	Disease	D004827
6153967	544	553	enflurane	Chemical	D004737
6153967	603	610	seizure	Disease	D012640
6153967	639	648	enflurane	Chemical	D004737
6153967	746	755	enflurane	Chemical	D004737
6153967	804	813	epileptic	Disease	D004827
6153967	CID	D004737	D012640

3183120|t|Reversible cerebral lesions associated with tiazofurin usage: MR demonstration.
3183120|a|Tiazofurin is an experimental chemotherapeutic agent currently undergoing clinical evaluation. We report our results with magnetic resonance (MR) in demonstrating reversible cerebral abnormalities concurrent with the use of this drug. The abnormalities on MR were correlated with findings on CT as well as with cerebral angiography. The utility of MR in the evaluation of patients receiving this new agent is illustrated.
3183120	11	27	cerebral lesions	Disease	D001927
3183120	44	54	tiazofurin	Chemical	C033706
3183120	80	90	Tiazofurin	Chemical	C033706
3183120	254	276	cerebral abnormalities	Disease	D001927
3183120	CID	C033706	D001927

3120485|t|Antagonism of diazepam-induced sedative effects by Ro15-1788 in patients after surgery under lumbar epidural block. A double-blind placebo-controlled investigation of efficacy and safety.
3120485|a|The aim of this study was to assess the efficacy of Ro15-1788 and a placebo in reversing diazepam-induced effects after surgery under epidural block, and to evaluate the local tolerance and general safety of Ro15-1788. Fifty-seven patients were sedated with diazepam for surgery under epidural anaesthesia. Antagonism of diazepam-induced effects by Ro15-1788 was investigated postoperatively in a double-blind placebo-controlled trial. The patient's subjective assessment of mood rating, an objective test of performance, a test for amnesia, and vital signs were recorded for up to 300 min after administration of the trial drug. No significant differences between the two groups were observed for mood rating, amnesia, or vital signs. The Ro15-1788 group showed a significant improvement in the performance test up to 120 min after administration of the drug. There was no evidence of reaction at the injection site.
3120485	14	22	diazepam	Chemical	D003975
3120485	51	60	Ro15-1788	Chemical	D005442
3120485	240	249	Ro15-1788	Chemical	D005442
3120485	277	285	diazepam	Chemical	D003975
3120485	396	405	Ro15-1788	Chemical	D005442
3120485	446	454	diazepam	Chemical	D003975
3120485	509	517	diazepam	Chemical	D003975
3120485	537	546	Ro15-1788	Chemical	D005442
3120485	721	728	amnesia	Disease	D000647
3120485	899	906	amnesia	Disease	D000647
3120485	928	937	Ro15-1788	Chemical	D005442
3120485	CID	D003975	D000647

2886572|t|Enhanced stimulus-induced neurotransmitter overflow in epinephrine-induced hypertensive rats is not mediated by prejunctional beta-adrenoceptor activation.
2886572|a|The present study examines the effect of 6-day epinephrine treatment (100 micrograms/kg per h, s.c.) on stimulus-induced (1 Hz) endogenous neurotransmitter overflow from the isolated perfused kidney of vehicle- and epinephrine-treated rats. Renal catecholamine stores and stimulus-induced overflow in the vehicle-treated group consisted of norepinephrine only. However, epinephrine treatment resulted in the incorporation of epinephrine into renal catecholamine stores such that approximately 40% of the catecholamine present was epinephrine while the norepinephrine content was reduced by a similar degree. Total tissue catecholamine content of the kidney on a molar basis was unchanged. Stimulus-induced fractional overflow of neurotransmitter from the epinephrine-treated kidneys was approximately twice normal and consisted of both norepinephrine and epinephrine in proportions similar to those found in the kidney. This difference in fractional overflow between groups was not affected by neuronal and extraneuronal uptake blockade. Propranolol had no effect on stimulus-induced overflow in either group. Phentolamine increased stimulus-induced overflow in both groups although the increment in overflow was greater in the epinephrine-treated group. In conclusion, chronic epinephrine treatment results in enhanced fractional neurotransmitter overflow. However, neither alterations in prejunctional beta-adrenoceptor influences nor alterations in neuronal and extraneuronal uptake mechanisms appear to be responsible for this alteration. Furthermore, data obtained with phentolamine alone do not suggest alpha-adrenoceptor desensitization as the cause of the enhanced neurotransmitter overflow after epinephrine treatment.
2886572	55	66	epinephrine	Chemical	D004837
2886572	75	87	hypertensive	Disease	D006973
2886572	203	214	epinephrine	Chemical	D004837
2886572	371	382	epinephrine	Chemical	D004837
2886572	403	416	catecholamine	Chemical	D002395
2886572	496	510	norepinephrine	Chemical	D009638
2886572	526	537	epinephrine	Chemical	D004837
2886572	581	592	epinephrine	Chemical	D004837
2886572	604	617	catecholamine	Chemical	D002395
2886572	660	673	catecholamine	Chemical	D002395
2886572	686	697	epinephrine	Chemical	D004837
2886572	708	722	norepinephrine	Chemical	D009638
2886572	777	790	catecholamine	Chemical	D002395
2886572	911	922	epinephrine	Chemical	D004837
2886572	992	1006	norepinephrine	Chemical	D009638
2886572	1011	1022	epinephrine	Chemical	D004837
2886572	1194	1205	Propranolol	Chemical	D011433
2886572	1266	1278	Phentolamine	Chemical	D010646
2886572	1384	1395	epinephrine	Chemical	D004837
2886572	1434	1445	epinephrine	Chemical	D004837
2886572	1731	1743	phentolamine	Chemical	D010646
2886572	1861	1872	epinephrine	Chemical	D004837
2886572	CID	D004837	D006973

1079693|t|Ocular manifestations of juvenile rheumatoid arthritis.
1079693|a|We followed 210 cases of juvenile rheumatoid arthritis closely for eleven years. Thirty-six of the 210 patients (17.2%) developed iridocyclitis. Iridocyclitis was seen most frequently in young female patients (0 to 4 years) with the monoarticular or pauciatricular form of the arthritis. However, 30% of the patients developed uveitis after 16 years of age. Although 61% of patients had a noncontributory ocular history on entry, 42% had active uveitis on entry. Our approach was effective in detecting uveitis in new cases and exacerbations of uveitis in established cases. Forty-four percent of patients with uveitis had one or more identifiable signs or symptoms, such as red eye, ocular pain, decreased visual acuity, or photophobia, in order of decreasing frequency. Even after early detection and prompt treatment, 41% of cases of uveitis did not respond to more than six months of intensive topical treatment with corticosteroids and mydriatics. Despite this, there was a dramatic decrease in the 50% incidence of blinding complications of uveitis cited in earlier studies. Cataract and band keratopathy occurred in only 22 and 13% of our group, respectively. We used chloroquine or hydroxychloroquine in 173 of 210 cases and found only one case of chorioretinopathy attributable to these drugs. Systemically administered corticosteroids were used in 75 of 210 cases; a significant number of posterior subcapsular cataracts was found. Typical keratoconjunctivitis sicca developed in three of the uveitis cases. This association with uveitis and JRA was not noted previously. Surgical treatment of cataracts, band keratopathy, and glaucoma achieved uniformly discouraging results.
1079693	25	54	juvenile rheumatoid arthritis	Disease	D001171
1079693	81	110	juvenile rheumatoid arthritis	Disease	D001171
1079693	186	199	iridocyclitis	Disease	D015863
1079693	201	214	Iridocyclitis	Disease	D015863
1079693	333	342	arthritis	Disease	D001168
1079693	383	390	uveitis	Disease	D014605
1079693	501	508	uveitis	Disease	D014605
1079693	559	566	uveitis	Disease	D014605
1079693	601	608	uveitis	Disease	D014605
1079693	667	674	uveitis	Disease	D014605
1079693	740	751	ocular pain	Disease	D058447
1079693	753	776	decreased visual acuity	Disease	D014786
1079693	781	792	photophobia	Disease	D020795
1079693	893	900	uveitis	Disease	D014605
1079693	977	992	corticosteroids	Chemical	D000305
1079693	1103	1110	uveitis	Disease	D014605
1079693	1137	1145	Cataract	Disease	D002386
1079693	1150	1166	band keratopathy	Disease	C562399
1079693	1231	1242	chloroquine	Chemical	D002738
1079693	1246	1264	hydroxychloroquine	Chemical	D006886
1079693	1312	1329	chorioretinopathy	Disease	D012164
1079693	1385	1400	corticosteroids	Chemical	D000305
1079693	1477	1486	cataracts	Disease	D002386
1079693	1506	1526	keratoconjunctivitis	Disease	D007637
1079693	1559	1566	uveitis	Disease	D014605
1079693	1596	1603	uveitis	Disease	D014605
1079693	1660	1669	cataracts	Disease	D002386
1079693	1671	1687	band keratopathy	Disease	C562399
1079693	1693	1701	glaucoma	Disease	D005901
1079693	CID	D006886	D012164

803783|t|Water intoxication associated with oxytocin administration during saline-induced abortion.
803783|a|Four cases of water intoxication in connection with oxytocin administration during saline-induced abortions are described. The mechanism of water intoxication is discussed in regard to these cases. Oxytocin administration during midtrimester-induced abortions is advocated only if it can be carried out under careful observations of an alert nursing staff, aware of the symptoms of water intoxication and instructed to watch the diuresis and report such early signs of the syndrome as asthenia, muscular irritability, or headaches. The oxytocin should be given only in Ringers lactate or, alternately, in Ringers lactate and a 5 per cent dextrose and water solutions. The urinary output should be monitored and the oxytocin administration discontinued and the serum electrolytes checked if the urinary output decreases. The oxytocin should not be administered in excess of 36 hours. If the patient has not aborted by then the oxytocin should be discontinued for 10 to 12 hours in order to perform electrolyte determinations and correct any electrolyte imbalance.
803783	0	18	Water intoxication	Disease	D014869
803783	35	43	oxytocin	Chemical	D010121
803783	81	89	abortion	Disease	D000031
803783	105	123	water intoxication	Disease	D014869
803783	143	151	oxytocin	Chemical	D010121
803783	189	198	abortions	Disease	D000031
803783	231	249	water intoxication	Disease	D014869
803783	289	297	Oxytocin	Chemical	D010121
803783	341	350	abortions	Disease	D000031
803783	473	491	water intoxication	Disease	D014869
803783	576	584	asthenia	Disease	D001247
803783	595	607	irritability	Disease	D001523
803783	612	621	headaches	Disease	D006261
803783	627	635	oxytocin	Chemical	D010121
803783	668	675	lactate	Chemical	D019344
803783	704	711	lactate	Chemical	D019344
803783	729	737	dextrose	Chemical	D005947
803783	806	814	oxytocin	Chemical	D010121
803783	915	923	oxytocin	Chemical	D010121
803783	1017	1025	oxytocin	Chemical	D010121
803783	CID	D010121	D014869

