10091617|a|OBJECTIVES: The United Kingdom Parkinson's Disease Research Group (UKPDRG) trial found an increased mortality in patients with Parkinson's disease (PD) randomized to receive 10 mg selegiline per day and L-dopa compared with those taking L-dopa alone. Recently, we found that therapy with selegiline and L-dopa was associated with selective systolic orthostatic hypotension which was abolished by withdrawal of selegiline. This unwanted effect on postural blood pressure was not the result of underlying autonomic failure. The aims of this study were to confirm our previous findings in a separate cohort of patients and to determine the time course of the cardiovascular consequences of stopping selegiline in the expectation that this might shed light on the mechanisms by which the drug causes orthostatic hypotension. METHODS: The cardiovascular responses to standing and head-up tilt were studied repeatedly in PD patients receiving selegiline and as the drug was withdrawn. RESULTS: Head-up tilt caused systolic orthostatic hypotension which was marked in six of 20 PD patients on selegiline, one of whom lost consciousness with unrecordable blood pressures. A lesser degree of orthostatic hypotension occurred with standing. Orthostatic hypotension was ameliorated 4 days after withdrawal of selegiline and totally abolished 7 days after discontinuation of the drug. Stopping selegiline also significantly reduced the supine systolic and diastolic blood pressures consistent with a previously undescribed supine pressor action. CONCLUSION: This study confirms our previous finding that selegiline in combination with L-dopa is associated with selective orthostatic hypotension. The possibilities that these cardiovascular findings might be the result of non-selective inhibition of monoamine oxidase or of amphetamine and metamphetamine are discussed.
10091617|t|Selegiline-induced postural hypotension in Parkinson's disease: a longitudinal study on the effects of drug withdrawal.
10091617	0	10	Selegiline	Chemical	D012642
10091617	19	39	postural hypotension	Disease	D007024
10091617	43	62	Parkinson's disease	Disease	D010300
10091617	151	170	Parkinson's Disease	Disease	D010300
10091617	247	266	Parkinson's disease	Disease	D010300
10091617	268	270	PD	Disease	D010300
10091617	300	310	selegiline	Chemical	D012642
10091617	323	329	L-dopa	Chemical	D007980
10091617	357	363	L-dopa	Chemical	D007980
10091617	408	418	selegiline	Chemical	D012642
10091617	423	429	L-dopa	Chemical	D007980
10091617	460	492	systolic orthostatic hypotension	Disease	D007024
10091617	530	540	selegiline	Chemical	D012642
10091617	816	826	selegiline	Chemical	D012642
10091617	916	939	orthostatic hypotension	Disease	D007024
10091617	1035	1037	PD	Disease	D010300
10091617	1057	1067	selegiline	Chemical	D012642
10091617	1128	1160	systolic orthostatic hypotension	Disease	D007024
10091617	1191	1193	PD	Disease	D010300
10091617	1206	1216	selegiline	Chemical	D012642
10091617	1303	1326	orthostatic hypotension	Disease	D007024
10091617	1351	1374	Orthostatic hypotension	Disease	D007024
10091617	1418	1428	selegiline	Chemical	D012642
10091617	1502	1512	selegiline	Chemical	D012642
10091617	1532	1589	reduced the supine systolic and diastolic blood pressures	Disease	D007024
10091617	1712	1722	selegiline	Chemical	D012642
10091617	1743	1749	L-dopa	Chemical	D007980
10091617	1779	1802	orthostatic hypotension	Disease	D007024
10091617	1932	1943	amphetamine	Chemical	D000661
10091617	1948	1962	metamphetamine	Chemical	D008694
10091617	induced	D012642	D007024
10091617	treated	D012642	D010300
10091617	treated	D007980	D010300
10193204|a|Tetrandrine (TET) and fangchinoline (FAN) are two naturally occurring analogues with a bisbenzylisoquinoline structure. The present study was undertaken to investigate the effects of TET and FAN on the experimental thrombosis induced by collagen plus epinephrine (EP) in mice, and platelet aggregation and blood coagulation in vitro. In the in vivo study, the administration (50 mg/kg, i.p.) of TET and FAN in mice showed the inhibition of thrombosis by 55% and 35%, respectively, while acetylsalicylic acid (ASA, 50 mg/kg, i.p.), a positive control, showed only 30% inhibition. In the vitro human platelet aggregations induced by the agonists used in tests, TET and FAN showed the inhibitions dose dependently. In addition, neither TET nor FAN showed any anticoagulation activities in the measurement of the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT) using human-citrated plasma. These results suggest that antithrombosis of TET and FAN in mice may be mainly related to the antiplatelet aggregation activities.
10193204|t|Effects of tetrandrine and fangchinoline on experimental thrombosis in mice and human platelet aggregation.
10193204	11	22	tetrandrine	Chemical	C009438
10193204	27	40	fangchinoline	Chemical	C060802
10193204	57	67	thrombosis	Disease	D013927
10193204	86	106	platelet aggregation	Disease	D001791
10193204	108	119	Tetrandrine	Chemical	C009438
10193204	121	124	TET	Chemical	C009438
10193204	130	143	fangchinoline	Chemical	C060802
10193204	145	148	FAN	Chemical	C060802
10193204	195	216	bisbenzylisoquinoline	Chemical	D044182
10193204	291	294	TET	Chemical	C009438
10193204	299	302	FAN	Chemical	C060802
10193204	323	333	thrombosis	Disease	D013927
10193204	359	370	epinephrine	Chemical	D004837
10193204	372	374	EP	Chemical	D004837
10193204	389	409	platelet aggregation	Disease	D001791
10193204	414	431	blood coagulation	Disease	D001778
10193204	503	506	TET	Chemical	C009438
10193204	511	514	FAN	Chemical	C060802
10193204	548	558	thrombosis	Disease	D013927
10193204	595	615	acetylsalicylic acid	Chemical	D001241
10193204	617	620	ASA	Chemical	D001241
10193204	706	727	platelet aggregations	Disease	D001791
10193204	767	770	TET	Chemical	C009438
10193204	775	778	FAN	Chemical	C060802
10193204	841	844	TET	Chemical	C009438
10193204	849	852	FAN	Chemical	C060802
10193204	1082	1085	TET	Chemical	C009438
10193204	1090	1093	FAN	Chemical	C060802
10193204	treated	C009438	D013927
10193204	treated	C060802	D013927
10193204	induced	D004837	D013927
10193204	induced	D004837	D001791
10193204	treated	D001241	D013927
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|t|Urine N-acetyl-beta-D-glucosaminidase--a marker of tubular 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	induced	D011692	D005198
10193809	induced	D011692	D011507
10342929|a|The estimated incidence of angioedema during angiotensin-converting enzyme (ACE) inhibitor treatment is between 1 and 7 per thousand patients. This potentially serious adverse effect is often preceded by minor manifestations that may serve as a warning.
10342929|t|Angioedema due to ACE inhibitors: common and inadequately diagnosed.
10342929	0	10	Angioedema	Disease	D000799
10342929	18	32	ACE inhibitors	Chemical	D000806
10342929	96	106	angioedema	Disease	D000799
10342929	114	159	angiotensin-converting enzyme (ACE) inhibitor	Chemical	D000806
10342929	induced	D000806	D000799
10365197|a|This paper attempts to examine and compare prevalence rates and symptom patterns of DSM substance-induced and other mood disorders. 243 cocaine-dependent outpatients with cocaine-induced mood disorder (CIMD), other mood disorders, or no mood disorder were compared on measures of psychiatric symptoms. The prevalence rate for CIMD was 12% at baseline. Introduction of the DSM-IV diagnosis of CIMD did not substantially affect rates of the other depressive disorders. Patients with CIMD had symptom severity levels between those of patients with and without a mood disorder. These findings suggest some validity for the new DSM-IV diagnosis of CIMD, but also suggest that it requires further specification and replication.
10365197|t|Cocaine-induced mood disorder: prevalence rates and psychiatric symptoms in an outpatient cocaine-dependent sample.
10365197	0	7	Cocaine	Chemical	D003042
10365197	16	29	mood disorder	Disease	D019964
10365197	52	63	psychiatric	Disease	D001523
10365197	90	97	cocaine	Chemical	D003042
10365197	232	246	mood disorders	Disease	D019964
10365197	252	259	cocaine	Chemical	D003042
10365197	287	294	cocaine	Chemical	D003042
10365197	303	316	mood disorder	Disease	D019964
10365197	318	322	CIMD	Disease	D019970
10365197	331	345	mood disorders	Disease	D019964
10365197	353	366	mood disorder	Disease	D019964
10365197	396	407	psychiatric	Disease	D001523
10365197	442	446	CIMD	Disease	D019970
10365197	508	512	CIMD	Disease	D019970
10365197	561	581	depressive disorders	Disease	D003866
10365197	597	601	CIMD	Disease	D019970
10365197	675	688	mood disorder	Disease	D019964
10365197	759	763	CIMD	Disease	D019970
10365197	induced	D003042	D001523
10365197	induced	D003042	D019964
10365197	induced	D003042	D019970
10457883|a|A case of recurarization in the recovery room is reported. Accumulation of atracurium in the intravenous line led to recurarization after flushing the line in the recovery room. A respiratory arrest with severe desaturation and bradycardia occurred. Circumstances leading to this event and the mechanisms enabling a neuromuscular blockade to occur, following the administration of a small dose of relaxant, are discussed.
10457883|t|Recurarization in the recovery room.
10457883	112	122	atracurium	Chemical	D001279
10457883	217	235	respiratory arrest	Disease	D012131
10457883	248	260	desaturation	Disease	D001049
10457883	265	276	bradycardia	Disease	D001919
10457883	353	375	neuromuscular blockade	Disease	D020879
10457883	induced	D001279	D012131
10457883	induced	D001279	D001049
10457883	induced	D001279	D001919
10669626|a|The present studies demonstrate that growth and vitamin D treatment enhance the extent of artery calcification in rats given sufficient doses of Warfarin to inhibit gamma-carboxylation of matrix Gla protein, a calcification inhibitor known to be expressed by smooth muscle cells and macrophages in the artery wall. The first series of experiments examined the influence of age and growth status on artery calcification in Warfarin-treated rats. Treatment for 2 weeks with Warfarin caused massive focal calcification of the artery media in 20-day-old rats and less extensive focal calcification in 42-day-old rats. In contrast, no artery calcification could be detected in 10-month-old adult rats even after 4 weeks of Warfarin treatment. To directly examine the importance of growth to Warfarin-induced artery calcification in animals of the same age, 20-day-old rats were fed for 2 weeks either an ad libitum diet or a 6-g/d restricted diet that maintains weight but prevents growth. Concurrent treatment of both dietary groups with Warfarin produced massive focal calcification of the artery media in the ad libitum-fed rats but no detectable artery calcification in the restricted-diet, growth-inhibited group. Although the explanation for the association between artery calcification and growth status cannot be determined from the present study, there was a relationship between higher serum phosphate and susceptibility to artery calcification, with 30% higher levels of serum phosphate in young, ad libitum-fed rats compared with either of the groups that was resistant to Warfarin-induced artery calcification, ie, the 10-month-old rats and the restricted-diet, growth-inhibited young rats. This observation suggests that increased susceptibility to Warfarin-induced artery calcification could be related to higher serum phosphate levels. The second set of experiments examined the possible synergy between vitamin D and Warfarin in artery calcification. High doses of vitamin D are known to cause calcification of the artery media in as little as 3 to 4 days. High doses of the vitamin K antagonist Warfarin are also known to cause calcification of the artery media, but at treatment times of 2 weeks or longer yet not at 1 week. In the current study, we investigated the synergy between these 2 treatments and found that concurrent Warfarin administration dramatically increased the extent of calcification in the media of vitamin D-treated rats at 3 and 4 days. There was a close parallel between the effect of vitamin D dose on artery calcification and the effect of vitamin D dose on the elevation of serum calcium, which suggests that vitamin D may induce artery calcification through its effect on serum calcium. Because Warfarin treatment had no effect on the elevation in serum calcium produced by vitamin D, the synergy between Warfarin and vitamin D is probably best explained by the hypothesis that Warfarin inhibits the activity of matrix Gla protein as a calcification inhibitor. High levels of matrix Gla protein are found at sites of artery calcification in rats treated with vitamin D plus Warfarin, and chemical analysis showed that the protein that accumulated was indeed not gamma-carboxylated. These observations indicate that although the gamma-carboxyglutamate residues of matrix Gla protein are apparently required for its function as a calcification inhibitor, they are not required for its accumulation at calcification sites.
10669626|t|Warfarin-induced artery calcification is accelerated by growth and vitamin D.
10669626	0	8	Warfarin	Chemical	D014859
10669626	17	37	artery calcification	Disease	D061205
10669626	67	76	vitamin D	Chemical	D014807
10669626	126	135	vitamin D	Chemical	D014807
10669626	168	188	artery calcification	Disease	D061205
10669626	223	231	Warfarin	Chemical	D014859
10669626	288	301	calcification	Disease	D002114
10669626	476	496	artery calcification	Disease	D061205
10669626	500	508	Warfarin	Chemical	D014859
10669626	550	558	Warfarin	Chemical	D014859
10669626	580	607	calcification of the artery	Disease	D061205
10669626	658	671	calcification	Disease	D002114
10669626	708	728	artery calcification	Disease	D061205
10669626	796	804	Warfarin	Chemical	D014859
10669626	864	872	Warfarin	Chemical	D014859
10669626	881	901	artery calcification	Disease	D061205
10669626	1112	1120	Warfarin	Chemical	D014859
10669626	1144	1171	calcification of the artery	Disease	D061205
10669626	1223	1243	artery calcification	Disease	D061205
10669626	1345	1365	artery calcification	Disease	D061205
10669626	1475	1484	phosphate	Chemical	D010710
10669626	1507	1527	artery calcification	Disease	D061205
10669626	1561	1570	phosphate	Chemical	D010710
10669626	1658	1666	Warfarin	Chemical	D014859
10669626	1675	1695	artery calcification	Disease	D061205
10669626	1836	1844	Warfarin	Chemical	D014859
10669626	1853	1873	artery calcification	Disease	D061205
10669626	1907	1916	phosphate	Chemical	D010710
10669626	1993	2002	vitamin D	Chemical	D014807
10669626	2007	2015	Warfarin	Chemical	D014859
10669626	2019	2039	artery calcification	Disease	D061205
10669626	2055	2064	vitamin D	Chemical	D014807
10669626	2084	2111	calcification of the artery	Disease	D061205
10669626	2165	2174	vitamin K	Chemical	D014812
10669626	2186	2194	Warfarin	Chemical	D014859
10669626	2219	2246	calcification of the artery	Disease	D061205
10669626	2420	2428	Warfarin	Chemical	D014859
10669626	2481	2494	calcification	Disease	D002114
10669626	2511	2520	vitamin D	Chemical	D014807
10669626	2600	2609	vitamin D	Chemical	D014807
10669626	2618	2638	artery calcification	Disease	D061205
10669626	2657	2666	vitamin D	Chemical	D014807
10669626	2698	2705	calcium	Chemical	D002118
10669626	2727	2736	vitamin D	Chemical	D014807
10669626	2748	2768	artery calcification	Disease	D061205
10669626	2797	2804	calcium	Chemical	D002118
10669626	2814	2822	Warfarin	Chemical	D014859
10669626	2873	2880	calcium	Chemical	D002118
10669626	2893	2902	vitamin D	Chemical	D014807
10669626	2924	2932	Warfarin	Chemical	D014859
10669626	2937	2946	vitamin D	Chemical	D014807
10669626	2997	3005	Warfarin	Chemical	D014859
10669626	3055	3068	calcification	Disease	D002114
10669626	3136	3156	artery calcification	Disease	D061205
10669626	3178	3187	vitamin D	Chemical	D014807
10669626	3193	3201	Warfarin	Chemical	D014859
10669626	3281	3299	gamma-carboxylated	Chemical	D015055
10669626	3347	3369	gamma-carboxyglutamate	Chemical	D015055
10669626	3447	3460	calcification	Disease	D002114
10669626	3518	3531	calcification	Disease	D002114
10669626	induced	D014859	D061205
10669626	induced	D014807	D061205
10669626	induced	D010710	D061205
10669626	treated	D014812	D061205
10704919|a|Tamoxifen (TAM), the antiestrogenic drug most widely prescribed in the chemotherapy of breast cancer, induces changes in normal discoid shape of erythrocytes and hemolytic anemia. This work evaluates the effects of TAM on isolated human erythrocytes, attempting to identify the underlying mechanisms on TAM-induced hemolytic anemia and the involvement of biomembranes in its cytostatic action mechanisms. TAM induces hemolysis of erythrocytes as a function of concentration. The extension of hemolysis is variable with erythrocyte samples, but 12.5 microM TAM induces total hemolysis of all tested suspensions. Despite inducing extensive erythrocyte lysis, TAM does not shift the osmotic fragility curves of erythrocytes. The hemolytic effect of TAM is prevented by low concentrations of alpha-tocopherol (alpha-T) and alpha-tocopherol acetate (alpha-TAc) (inactivated functional hydroxyl) indicating that TAM-induced hemolysis is not related to oxidative membrane damage. This was further evidenced by absence of oxygen consumption and hemoglobin oxidation both determined in parallel with TAM-induced hemolysis. Furthermore, it was observed that TAM inhibits the peroxidation of human erythrocytes induced by AAPH, thus ruling out TAM-induced cell oxidative stress. Hemolysis caused by TAM was not preceded by the leakage of K(+) from the cells, also excluding a colloid-osmotic type mechanism of hemolysis, according to the effects on osmotic fragility curves. However, TAM induces release of peripheral proteins of membrane-cytoskeleton and cytosol proteins essentially bound to band 3. Either alpha-T or alpha-TAc increases membrane packing and prevents TAM partition into model membranes. These effects suggest that the protection from hemolysis by tocopherols is related to a decreased TAM incorporation in condensed membranes and the structural damage of the erythrocyte membrane is consequently avoided. Therefore, TAM-induced hemolysis results from a structural perturbation of red cell membrane, leading to changes in the framework of the erythrocyte membrane and its cytoskeleton caused by its high partition in the membrane. These defects explain the abnormal erythrocyte shape and decreased mechanical stability promoted by TAM, resulting in hemolytic anemia. Additionally, since membrane leakage is a final stage of cytotoxicity, the disruption of the structural characteristics of biomembranes by TAM may contribute to the multiple mechanisms of its anticancer action.
10704919|t|Hemolysis of human erythrocytes induced by tamoxifen is related to disruption of membrane structure.
10704919	0	9	Hemolysis	Disease	D006461
10704919	43	52	tamoxifen	Chemical	D013629
10704919	101	110	Tamoxifen	Chemical	D013629
10704919	112	115	TAM	Chemical	D013629
10704919	188	201	breast cancer	Disease	D001943
10704919	263	279	hemolytic anemia	Disease	D000743
10704919	316	319	TAM	Chemical	D013629
10704919	404	407	TAM	Chemical	D013629
10704919	416	432	hemolytic anemia	Disease	D000743
10704919	506	509	TAM	Chemical	D013629
10704919	518	527	hemolysis	Disease	D006461
10704919	593	602	hemolysis	Disease	D006461
10704919	657	660	TAM	Chemical	D013629
10704919	675	684	hemolysis	Disease	D006461
10704919	758	761	TAM	Chemical	D013629
10704919	827	836	hemolytic	Disease	D006461
10704919	847	850	TAM	Chemical	D013629
10704919	889	905	alpha-tocopherol	Chemical	D024502
10704919	907	914	alpha-T	Chemical	D024502
10704919	920	944	alpha-tocopherol acetate	Chemical	D024502
10704919	946	955	alpha-TAc	Chemical	D024502
10704919	981	989	hydroxyl	Chemical	D017665
10704919	1007	1010	TAM	Chemical	D013629
10704919	1019	1028	hemolysis	Disease	D006461
10704919	1115	1121	oxygen	Chemical	D010100
10704919	1192	1195	TAM	Chemical	D013629
10704919	1204	1213	hemolysis	Disease	D006461
10704919	1249	1252	TAM	Chemical	D013629
10704919	1312	1316	AAPH	Chemical	C046728
10704919	1334	1337	TAM	Chemical	D013629
10704919	1369	1378	Hemolysis	Disease	D006461
10704919	1389	1392	TAM	Chemical	D013629
10704919	1428	1429	K	Chemical	D011188
10704919	1500	1509	hemolysis	Disease	D006461
10704919	1574	1577	TAM	Chemical	D013629
10704919	1699	1706	alpha-T	Chemical	D024502
10704919	1710	1719	alpha-TAc	Chemical	D024502
10704919	1760	1763	TAM	Chemical	D013629
10704919	1843	1852	hemolysis	Disease	D006461
10704919	1856	1867	tocopherols	Chemical	D024505
10704919	1894	1897	TAM	Chemical	D013629
10704919	2025	2028	TAM	Chemical	D013629
10704919	2037	2046	hemolysis	Disease	D006461
10704919	2339	2342	TAM	Chemical	D013629
10704919	2357	2373	hemolytic anemia	Disease	D000743
10704919	2514	2517	TAM	Chemical	D013629
10704919	induced	D013629	D006461
10704919	treated	D024502	D000743
10704919	induced	D013629	D000743
10704919	treated	D024505	D000743
10704919	treated	D024502	D006461
10721819|a|It has been shown that bromocriptine-induced tachycardia, which persisted after adrenalectomy, is (i) mediated by central dopamine D2 receptor activation and (ii) reduced by 5-day isoproterenol pretreatment, supporting therefore the hypothesis that this effect is dependent on sympathetic outflow to the heart. This study was conducted to examine whether prolonged pretreatment with isoproterenol could abolish bromocriptine-induced tachycardia in conscious rats. Isoproterenol pretreatment for 15 days caused cardiac hypertrophy without affecting baseline blood pressure and heart rate. In control rats, intravenous bromocriptine (150 microg/kg) induced significant hypotension and tachycardia. Bromocriptine-induced hypotension was unaffected by isoproterenol pretreatment, while tachycardia was reversed to significant bradycardia, an effect that was partly reduced by i.v. domperidone (0.5 mg/kg). Neither cardiac vagal nor sympathetic tone was altered by isoproterenol pretreatment. In isolated perfused heart preparations from isoproterenol-pretreated rats, the isoproterenol-induced maximal increase in left ventricular systolic pressure was significantly reduced, compared with saline-pretreated rats (the EC50 of the isoproterenol-induced increase in left ventricular systolic pressure was enhanced approximately 22-fold). These results show that 15-day isoproterenol pretreatment not only abolished but reversed bromocriptine-induced tachycardia to bradycardia, an effect that is mainly related to further cardiac beta-adrenoceptor desensitization rather than to impairment of autonomic regulation of the heart. They suggest that, in normal conscious rats, the central tachycardia of bromocriptine appears to predominate and to mask the bradycardia of this agonist at peripheral dopamine D2 receptors.
10721819|t|Effects of long-term pretreatment with isoproterenol on bromocriptine-induced tachycardia in conscious rats.
10721819	39	52	isoproterenol	Chemical	D007545
10721819	56	69	bromocriptine	Chemical	D001971
10721819	78	89	tachycardia	Disease	D013610
10721819	132	145	bromocriptine	Chemical	D001971
10721819	154	165	tachycardia	Disease	D013610
10721819	231	239	dopamine	Chemical	D004298
10721819	289	302	isoproterenol	Chemical	D007545
10721819	492	505	isoproterenol	Chemical	D007545
10721819	520	533	bromocriptine	Chemical	D001971
10721819	542	553	tachycardia	Disease	D013610
10721819	573	586	Isoproterenol	Chemical	D007545
10721819	619	638	cardiac hypertrophy	Disease	D006332
10721819	726	739	bromocriptine	Chemical	D001971
10721819	776	787	hypotension	Disease	D007022
10721819	792	803	tachycardia	Disease	D013610
10721819	805	818	Bromocriptine	Chemical	D001971
10721819	827	838	hypotension	Disease	D007022
10721819	857	870	isoproterenol	Chemical	D007545
10721819	891	902	tachycardia	Disease	D013610
10721819	931	942	bradycardia	Disease	D001919
10721819	986	997	domperidone	Chemical	D004294
10721819	1069	1082	isoproterenol	Chemical	D007545
10721819	1142	1155	isoproterenol	Chemical	D007545
10721819	1177	1190	isoproterenol	Chemical	D007545
10721819	1335	1348	isoproterenol	Chemical	D007545
10721819	1472	1485	isoproterenol	Chemical	D007545
10721819	1531	1544	bromocriptine	Chemical	D001971
10721819	1553	1564	tachycardia	Disease	D013610
10721819	1568	1579	bradycardia	Disease	D001919
10721819	1788	1799	tachycardia	Disease	D013610
10721819	1803	1816	bromocriptine	Chemical	D001971
10721819	1856	1867	bradycardia	Disease	D001919
10721819	1898	1906	dopamine	Chemical	D004298
10721819	induced	D007545	D006332
10721819	induced	D001971	D007022
10721819	induced	D007545	D001919
10721819	treated	D004294	D001919
10721819	induced	D001971	D013610
10721819	treated	D007545	D013610
10737864|a|Under controlled conditions, infant rats emit ultrasonic vocalizations during extreme cold exposure and after administration of the alpha(2) adrenoceptor agonist, clonidine. Previous investigations have determined that, in response to clonidine, ultrasound production increases through the 2nd-week postpartum and decreases thereafter. Given that sympathetic neural dominance exhibits a similar developmental pattern, and given that clonidine induces sympathetic withdrawal and bradycardia, we hypothesized that clonidine's developmental effects on cardiac rate and ultrasound production would mirror each other. Therefore, in the present experiment, the effects of clonidine administration (0.5 mg/kg) on cardiac rate and ultrasound production were examined in 2-, 8-, 15-, and 20-day-old rats. Age-related changes in ultrasound production corresponded with changes in cardiovascular variables, including baseline cardiac rate and clonidine-induced bradycardia. This experiment is discussed with regard to the hypothesis that ultrasound production is the acoustic by-product of a physiological maneuver that compensates for clonidine's detrimental effects on cardiovascular function.
10737864|t|A developmental analysis of clonidine's effects on cardiac rate and ultrasound production in infant rats.
10737864	28	37	clonidine	Chemical	D003000
10737864	269	278	clonidine	Chemical	D003000
10737864	341	350	clonidine	Chemical	D003000
10737864	539	548	clonidine	Chemical	D003000
10737864	584	595	bradycardia	Disease	D001919
10737864	618	627	clonidine	Chemical	D003000
10737864	772	781	clonidine	Chemical	D003000
10737864	1038	1047	clonidine	Chemical	D003000
10737864	1056	1067	bradycardia	Disease	D001919
10737864	1231	1240	clonidine	Chemical	D003000
10737864	induced	D003000	D001919
10739826|a|The epidemiological studies that assessed the risk of venous thromboembolism (VTE) associated with newer oral contraceptives (OC) did not distinguish between patterns of OC use, namely first-time users, repeaters and switchers. Data from a Transnational case-control study were used to assess the risk of VTE for the latter patterns of use, while accounting for duration of use. Over the period 1993-1996, 551 cases of VTE were identified in Germany and the UK along with 2066 controls. Totals of 128 cases and 650 controls were analysed for repeat use and 135 cases and 622 controls for switching patterns. The adjusted rate ratio of VTE for repeat users of third generation OC was 0.6 (95% CI:0.3-1.2) relative to repeat users of second generation pills, whereas it was 1.3 (95% CI:0.7-2.4) for switchers from second to third generation pills relative to switchers from third to second generation pills. We conclude that second and third generation agents are associated with equivalent risks of VTE when the same agent is used repeatedly after interruption periods or when users are switched between the two generations of pills. These analyses suggest that the higher risk observed for the newer OC in other studies may be the result of inadequate comparisons of pill users with different patterns of pill use.
10739826|t|Recurrent use of newer oral contraceptives and the risk of venous thromboembolism.
10739826	23	42	oral contraceptives	Chemical	D003276
10739826	59	81	venous thromboembolism	Disease	D054556
10739826	137	159	venous thromboembolism	Disease	D054556
10739826	161	164	VTE	Disease	D054556
10739826	188	207	oral contraceptives	Chemical	D003276
10739826	209	211	OC	Chemical	D003276
10739826	253	255	OC	Chemical	D003276
10739826	388	391	VTE	Disease	D054556
10739826	502	505	VTE	Disease	D054556
10739826	718	721	VTE	Disease	D054556
10739826	759	761	OC	Chemical	D003276
10739826	1081	1084	VTE	Disease	D054556
10739826	1283	1285	OC	Chemical	D003276
10739826	induced	D003276	D054556
10743446|a|We have examined the effect of systemic administration of ketamine and lidocaine on brush-evoked (dynamic) pain and punctate-evoked (static) hyperalgesia induced by capsaicin. In a randomized, double-blind, placebo-controlled, crossover study, we studied 12 volunteers in three experiments. Capsaicin 100 micrograms was injected intradermally on the volar forearm followed by an i.v. infusion of ketamine (bolus 0.1 mg kg-1 over 10 min followed by infusion of 7 micrograms kg-1 min-1), lidocaine 5 mg kg-1 or saline for 50 min. Infusion started 15 min after injection of capsaicin. The following were measured: spontaneous pain, pain evoked by punctate and brush stimuli (VAS), and areas of brush-evoked and punctate-evoked hyperalgesia. Ketamine reduced both the area of brush-evoked and punctate-evoked hyperalgesia significantly and it tended to reduce brush-evoked pain. Lidocaine reduced the area of punctate-evoked hyperalgesia significantly. It tended to reduce VAS scores of spontaneous pain but had no effect on evoked pain. The differential effects of ketamine and lidocaine on static and dynamic hyperalgesia suggest that the two types of hyperalgesia are mediated by separate mechanisms and have a distinct pharmacology.
10743446|t|Differential effects of systemically administered ketamine and lidocaine on dynamic and static hyperalgesia induced by intradermal capsaicin in humans.
10743446	50	58	ketamine	Chemical	D007649
10743446	63	72	lidocaine	Chemical	D008012
10743446	95	107	hyperalgesia	Disease	D006930
10743446	131	140	capsaicin	Chemical	D002211
10743446	210	218	ketamine	Chemical	D007649
10743446	223	232	lidocaine	Chemical	D008012
10743446	259	263	pain	Disease	D010146
10743446	293	305	hyperalgesia	Disease	D006930
10743446	317	326	capsaicin	Chemical	D002211
10743446	443	452	Capsaicin	Chemical	D002211
10743446	548	556	ketamine	Chemical	D007649
10743446	638	647	lidocaine	Chemical	D008012
10743446	723	732	capsaicin	Chemical	D002211
10743446	775	779	pain	Disease	D010146
10743446	781	785	pain	Disease	D010146
10743446	876	888	hyperalgesia	Disease	D006930
10743446	890	898	Ketamine	Chemical	D007649
10743446	957	969	hyperalgesia	Disease	D006930
10743446	1021	1025	pain	Disease	D010146
10743446	1027	1036	Lidocaine	Chemical	D008012
10743446	1073	1085	hyperalgesia	Disease	D006930
10743446	1147	1151	pain	Disease	D010146
10743446	1180	1184	pain	Disease	D010146
10743446	1214	1222	ketamine	Chemical	D007649
10743446	1227	1236	lidocaine	Chemical	D008012
10743446	1259	1271	hyperalgesia	Disease	D006930
10743446	1302	1314	hyperalgesia	Disease	D006930
10743446	treated	D007649	D010146
10743446	treated	D008012	D006930
10743446	treated	D008012	D010146
10743446	treated	D007649	D006930
10743446	induced	D002211	D010146
10743446	induced	D002211	D006930
10901305|a|BACKGROUND: There recently has been a resurgence in the utilization of ketamine, a unique anesthetic, for emergency-department procedures requiring sedation. The purpose of the present study was to examine the safety and efficacy of ketamine for sedation in the treatment of children's fractures in the emergency department. METHODS: One hundred and fourteen children (average age, 5.3 years; range, twelve months to ten years and ten months) who underwent closed reduction of an isolated fracture or dislocation in the emergency department at a level-I trauma center were prospectively evaluated. Ketamine hydrochloride was administered intravenously (at a dose of two milligrams per kilogram of body weight) in ninety-nine of the patients and intramuscularly (at a dose of four milligrams per kilogram of body weight) in the other fifteen. A board-certified emergency physician skilled in airway management supervised administration of the anesthetic, and the patients were monitored by a registered nurse. Any pain during the reduction was rated by the orthopaedic surgeon treating the patient according to the Children's Hospital of Eastern Ontario Pain Scale (CHEOPS). RESULTS: The average time from intravenous administration of ketamine to manipulation of the fracture or dislocation was one minute and thirty-six seconds (range, twenty seconds to five minutes), and the average time from intramuscular administration to manipulation was four minutes and forty-two seconds (range, sixty seconds to fifteen minutes). The average score according to the Children's Hospital of Eastern Ontario Pain Scale was 6.4 points (range, 5 to 10 points), reflecting minimal or no pain during fracture reduction. Adequate fracture reduction was obtained in 111 of the children. Ninety-nine percent (sixty-eight) of the sixty-nine parents present during the reduction were pleased with the sedation and would allow it to be used again in a similar situation. Patency of the airway and independent respiration were maintained in all of the patients. Blood pressure and heart rate remained stable. Minor side effects included nausea (thirteen patients), emesis (eight of the thirteen patients with nausea), clumsiness (evident as ataxic movements in ten patients), and dysphoric reaction (one patient). No long-term sequelae were noted, and no patients had hallucinations or nightmares. CONCLUSIONS: Ketamine reliably, safely, and quickly provided adequate sedation to effectively facilitate the reduction of children's fractures in the emergency department at our institution. Ketamine should only be used in an environment such as the emergency department, where proper one-on-one monitoring is used and board-certified physicians skilled in airway management are directly involved in the care of the patient.
10901305|t|Ketamine sedation for the reduction of children's fractures in the emergency department.
10901305	0	8	Ketamine	Chemical	D007649
10901305	50	59	fractures	Disease	D050723
10901305	160	168	ketamine	Chemical	D007649
10901305	322	330	ketamine	Chemical	D007649
10901305	375	384	fractures	Disease	D050723
10901305	578	586	fracture	Disease	D050723
10901305	590	601	dislocation	Disease	D004204
10901305	643	649	trauma	Disease	D014947
10901305	687	709	Ketamine hydrochloride	Chemical	D007649
10901305	1102	1106	pain	Disease	D010146
10901305	1242	1246	Pain	Disease	D010146
10901305	1324	1332	ketamine	Chemical	D007649
10901305	1356	1364	fracture	Disease	D050723
10901305	1368	1379	dislocation	Disease	D004204
10901305	1686	1690	Pain	Disease	D010146
10901305	1762	1766	pain	Disease	D010146
10901305	1774	1782	fracture	Disease	D050723
10901305	1803	1811	fracture	Disease	D050723
10901305	2204	2210	nausea	Disease	D009325
10901305	2232	2238	emesis	Disease	D014839
10901305	2276	2282	nausea	Disease	D009325
10901305	2285	2295	clumsiness	Disease	D001259
10901305	2308	2324	ataxic movements	Disease	D001259
10901305	2347	2365	dysphoric reaction	Disease	-1
10901305	2435	2449	hallucinations	Disease	D006212
10901305	2478	2486	Ketamine	Chemical	D007649
10901305	2598	2607	fractures	Disease	D050723
10901305	2656	2664	Ketamine	Chemical	D007649
10901305	treated	D007649	D050723
10901305	treated	D007649	D010146
10901305	induced	D007649	D014839
10901305	induced	D007649	D009325
11007689|a|The development of thrombotic microangiopathy (TMA) associated with the use of cyclosporine has been well documented. Treatments have included discontinuation or reduction of cyclosporine dose with or without concurrent plasma exchange, plasma infusion, anticoagulation, and intravenous immunoglobulin G infusion. However, for recipients of organ transplantation, removing the inciting agent is not without the attendant risk of precipitating acute rejection and graft loss. The last decade has seen the emergence of tacrolimus as a potent immunosuppressive agent with mechanisms of action virtually identical to those of cyclosporine. As a result, switching to tacrolimus has been reported to be a viable therapeutic option in the setting of cyclosporine-induced TMA. With the more widespread application of tacrolimus in organ transplantation, tacrolimus-associated TMA has also been recognized. However, literature regarding the incidence of the recurrence of TMA in patients exposed sequentially to cyclosporine and tacrolimus is limited. We report a case of a living donor renal transplant recipient who developed cyclosporine-induced TMA that responded to the withdrawal of cyclosporine in conjunction with plasmapheresis and fresh frozen plasma replacement therapy. Introduction of tacrolimus as an alternative immunosuppressive agent resulted in the recurrence of TMA and the subsequent loss of the renal allograft. Patients who are switched from cyclosporine to tacrolimus or vice versa should be closely monitored for the signs and symptoms of recurrent TMA.
11007689|t|Cyclosporine and tacrolimus-associated thrombotic microangiopathy.
11007689	0	12	Cyclosporine	Chemical	D016572
11007689	17	27	tacrolimus	Chemical	D016559
11007689	39	65	thrombotic microangiopathy	Disease	D057049
11007689	86	112	thrombotic microangiopathy	Disease	D057049
11007689	114	117	TMA	Disease	D057049
11007689	146	158	cyclosporine	Chemical	D016572
11007689	242	254	cyclosporine	Chemical	D016572
11007689	584	594	tacrolimus	Chemical	D016559
11007689	689	701	cyclosporine	Chemical	D016572
11007689	729	739	tacrolimus	Chemical	D016559
11007689	810	822	cyclosporine	Chemical	D016572
11007689	831	834	TMA	Disease	D057049
11007689	876	886	tacrolimus	Chemical	D016559
11007689	913	923	tacrolimus	Chemical	D016559
11007689	935	938	TMA	Disease	D057049
11007689	1030	1033	TMA	Disease	D057049
11007689	1070	1082	cyclosporine	Chemical	D016572
11007689	1087	1097	tacrolimus	Chemical	D016559
11007689	1186	1198	cyclosporine	Chemical	D016572
11007689	1207	1210	TMA	Disease	D057049
11007689	1247	1259	cyclosporine	Chemical	D016572
11007689	1356	1366	tacrolimus	Chemical	D016559
11007689	1439	1442	TMA	Disease	D057049
11007689	1522	1534	cyclosporine	Chemical	D016572
11007689	1538	1548	tacrolimus	Chemical	D016559
11007689	1631	1634	TMA	Disease	D057049
11007689	induced	D016572	D057049
11007689	induced	D016559	D057049
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|t|Electro-oculography, electroretinography, visual evoked potentials, and multifocal electroretinography in patients with vigabatrin-attributed visual field constriction.
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	induced	D020888	D014786
11147747|a|Many new serotonergic antidepressants have been introduced over the past decade. Although urinary incontinence is listed as one side effect of these drugs in their package inserts there is only one report in the literature. This concerns 2 male patients who experienced incontinence while taking venlafaxine. In the present paper the authors describe 2 female patients who developed incontinence secondary to the selective serotonin reuptake inhibitors paroxetine and sertraline, as well as a third who developed this side effect on venlafaxine. In 2 of the 3 cases the patients were also taking lithium carbonate and beta-blockers, both of which could have contributed to the incontinence. Animal studies suggest that incontinence secondary to serotonergic antidepressants could be mediated by the 5HT4 receptors found on the bladder. Further research is needed to delineate the frequency of this troubling side effect and how best to treat it.
11147747|t|Serotonergic antidepressants and urinary incontinence.
11147747	0	28	Serotonergic antidepressants	Chemical	D018490
11147747	33	53	urinary incontinence	Disease	D014549
11147747	64	92	serotonergic antidepressants	Chemical	D018490
11147747	145	165	urinary incontinence	Disease	D014549
11147747	325	337	incontinence	Disease	D014549
11147747	351	362	venlafaxine	Chemical	C047426
11147747	438	450	incontinence	Disease	D014549
11147747	478	487	serotonin	Chemical	D012701
11147747	508	518	paroxetine	Chemical	D017374
11147747	523	533	sertraline	Chemical	D020280
11147747	588	599	venlafaxine	Chemical	C047426
11147747	651	668	lithium carbonate	Chemical	D016651
11147747	732	744	incontinence	Disease	D014549
11147747	774	786	incontinence	Disease	D014549
11147747	800	828	serotonergic antidepressants	Chemical	D018490
11147747	Association	D016651	D014549
11147747	Association	D018490	D014549
11147747	induced	C047426	D014549
11147747	Association	D012701	D014549
11147747	induced	D017374	D014549
11147747	induced	D020280	D014549
11256525|a|We report the case of a 70-year-old hypertensive man with a solitary kidney and chronic renal insufficiency who developed two episodes of transient anuria after losartan administration. He was hospitalized for a myocardial infarction with pulmonary edema, treated with high-dose diuretics. Due to severe systolic dysfunction losartan was prescribed. Surprisingly, the first dose of 50 mg of losartan resulted in a sudden anuria, which lasted eight hours despite high-dose furosemide and amine infusion. One week later, by mistake, losartan was prescribed again and after the second dose of 50 mg, the patient developed a second episode of transient anuria lasting 10 hours. During these two episodes, his blood pressure diminished but no severe hypotension was noted. Ultimately, an arteriography showed a 70-80% renal artery stenosis. In this patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, angiotensin II receptor blockade by losartan probably induced a critical fall in glomerular filtration pressure. This case report highlights the fact that the angiotensin II receptor antagonist losartan can cause serious unexpected complications in patients with renovascular disease and should be used with extreme caution in this setting.
11256525|t|Repeated transient anuria following losartan administration in a patient with a solitary kidney.
11256525	19	25	anuria	Disease	D001002
11256525	36	44	losartan	Chemical	D019808
11256525	133	145	hypertensive	Disease	D006973
11256525	177	204	chronic renal insufficiency	Disease	D051436
11256525	245	251	anuria	Disease	D001002
11256525	258	266	losartan	Chemical	D019808
11256525	309	330	myocardial infarction	Disease	D009203
11256525	336	351	pulmonary edema	Disease	D011654
11256525	401	421	systolic dysfunction	Disease	D006331
11256525	422	430	losartan	Chemical	D019808
11256525	488	496	losartan	Chemical	D019808
11256525	518	524	anuria	Disease	D001002
11256525	569	579	furosemide	Chemical	D005665
11256525	584	589	amine	Chemical	D000588
11256525	628	636	losartan	Chemical	D019808
11256525	746	752	anuria	Disease	D001002
11256525	842	853	hypotension	Disease	D007022
11256525	910	931	renal artery stenosis	Disease	D012078
11256525	950	971	renal artery stenosis	Disease	D012078
11256525	986	999	heart failure	Disease	D006333
11256525	1076	1087	angiotensin	Chemical	D000809
11256525	1125	1139	angiotensin II	Chemical	D000804
11256525	1161	1169	losartan	Chemical	D019808
11256525	1284	1298	angiotensin II	Chemical	D000804
11256525	1319	1327	losartan	Chemical	D019808
11256525	1388	1408	renovascular disease	Disease	D014652
11256525	induced	D019808	D012078
11256525	treated	D019808	D006333
11256525	treated	D019808	D006973
11256525	induced	D019808	D001002
11256525	treated	D019808	D006331
11379838|a|BACKGROUND: Concerns about possible risks of switching to mania associated with antidepressants continue to interfere with the establishment of an optimal treatment paradigm for bipolar depression. METHOD: The response of 44 patients meeting DSM-IV criteria for bipolar disorder to naturalistic treatment was assessed for at least 6 weeks using the Montgomery-Asberg Depression Rating Scale and the Bech-Rafaelson Mania Rating Scale. Patients who experienced a manic or hypomanic switch were compared with those who did not on several variables including age, sex, diagnosis (DSM-IV bipolar I vs. bipolar II), number of previous manic episodes, type of antidepressant therapy used (electroconvulsive therapy vs. antidepressant drugs and, more particularly, selective serotonin reuptake inhibitors [SSRIs]), use and type of mood stabilizers (lithium vs. anticonvulsants), and temperament of the patient, assessed during a normothymic period using the hyperthymia component of the Semi-structured Affective Temperament Interview. RESULTS: Switches to hypomania or mania occurred in 27% of all patients (N = 12) (and in 24% of the subgroup of patients treated with SSRIs [8/33]); 16% (N = 7) experienced manic episodes, and 11% (N = 5) experienced hypomanic episodes. Sex, age, diagnosis (bipolar I vs. bipolar II), and additional treatment did not affect the risk of switching. The incidence of mood switches seemed not to differ between patients receiving an anticonvulsant and those receiving no mood stabilizer. In contrast, mood switches were less frequent in patients receiving lithium (15%, 4/26) than in patients not treated with lithium (44%, 8/18; p = .04). The number of previous manic episodes did not affect the probability of switching, whereas a high score on the hyperthymia component of the Semistructured Affective Temperament Interview was associated with a greater risk of switching (p = .008). CONCLUSION: The frequency of mood switching associated with acute antidepressant therapy may be reduced by lithium treatment. Particular attention should be paid to patients with a hyperthymic temperament, who have a greater risk of mood switches.
11379838|t|Antidepressant-induced mania in bipolar patients: identification of risk factors.
11379838	0	14	Antidepressant	Chemical	D000928
11379838	23	28	mania	Disease	D001714
11379838	32	39	bipolar	Disease	D001714
11379838	140	145	mania	Disease	D001714
11379838	162	177	antidepressants	Chemical	D000928
11379838	260	278	bipolar depression	Disease	D001714
11379838	344	360	bipolar disorder	Disease	D001714
11379838	543	548	manic	Disease	D001714
11379838	552	561	hypomanic	Disease	D001714
11379838	658	674	DSM-IV bipolar I	Disease	D001714
11379838	679	689	bipolar II	Disease	D001714
11379838	711	716	manic	Disease	D001714
11379838	735	749	antidepressant	Chemical	D000928
11379838	794	808	antidepressant	Chemical	D000928
11379838	849	878	serotonin reuptake inhibitors	Chemical	D017367
11379838	880	885	SSRIs	Chemical	D017367
11379838	923	930	lithium	Chemical	D008094
11379838	1131	1140	hypomania	Disease	D001714
11379838	1144	1149	mania	Disease	D001714
11379838	1244	1249	SSRIs	Chemical	D017367
11379838	1283	1288	manic	Disease	D001714
11379838	1327	1336	hypomanic	Disease	D001714
11379838	1368	1377	bipolar I	Disease	D001714
11379838	1382	1392	bipolar II	Disease	D001714
11379838	1663	1670	lithium	Chemical	D008094
11379838	1717	1724	lithium	Chemical	D008094
11379838	1770	1775	manic	Disease	D001714
11379838	2060	2074	antidepressant	Chemical	D000928
11379838	2101	2108	lithium	Chemical	D008094
11379838	induced	D000928	D001714
11379838	induced	D017367	D001714
11379838	treated	D008094	D001714
11419773|a|We describe a 25-year-old woman with pre-existing mitral valve prolapse who developed intractable ventricular fibrillation after consuming a "natural energy" guarana health drink containing a high concentration of caffeine. This case highlights the need for adequate labelling and regulation of such products.
11419773|t|Caffeine-induced cardiac arrhythmia: an unrecognised danger of healthfood products.
11419773	0	8	Caffeine	Chemical	D002110
11419773	17	35	cardiac arrhythmia	Disease	D001145
11419773	134	155	mitral valve prolapse	Disease	D008945
11419773	182	206	ventricular fibrillation	Disease	D014693
11419773	298	306	caffeine	Chemical	D002110
11419773	induced	D002110	D001145
11419773	Association	D002110	D008945
11419773	induced	D002110	D014693
1147734|a|This report presents the clinical, laboratory, and light and electron microscopic observations on a patient with chronic active (aggressive) hepatitis caused by the administration of propylthiouracil. This is an addition to the list of drugs that must be considered in the evaluation of chronic liver disease.
1147734|t|Liver disease caused by propylthiouracil.
1147734	0	13	Liver disease	Disease	D008107
1147734	24	40	propylthiouracil	Chemical	D011441
1147734	155	192	chronic active (aggressive) hepatitis	Disease	D006521
1147734	225	241	propylthiouracil	Chemical	D011441
1147734	337	350	liver disease	Disease	D008107
1147734	induced	D011441	D008107
1147734	induced	D011441	D006521
11569530|a|1. Torsades de pointes (TDP) is a potentially fatal ventricular tachycardia associated with increases in QT interval and monophasic action potential duration (MAPD). TDP is a side-effect that has led to withdrawal of several drugs from the market (e.g. terfenadine and terodiline). 2. The potential of compounds to cause TDP was evaluated by monitoring their effects on MAPD in dog. Four compounds known to increase QT interval and cause TDP were investigated: terfenadine, terodiline, cisapride and E4031. On the basis that only free drug in the systemic circulation will elicit a pharmacological response target, free concentrations in plasma were selected to mimic the free drug exposures in man. Infusion regimens were designed that rapidly achieved and maintained target-free concentrations of these drugs in plasma and data on the relationship between free concentration and changes in MAPD were obtained for these compounds. 3. These data indicate that the free ED50 in plasma for terfenadine (1.9 nM), terodiline (76 nM), cisapride (11 nM) and E4031 (1.9 nM) closely correlate with the free concentration in man causing QT effects. For compounds that have shown TDP in the clinic (terfenadine, terodiline, cisapride) there is little differentiation between the dog ED50 and the efficacious free plasma concentrations in man (< 10-fold) reflecting their limited safety margins. These data underline the need to maximize the therapeutic ratio with respect to TDP in potential development candidates and the importance of using free drug concentrations in pharmacokinetic/pharmacodynamic studies.
11569530|t|Pharmacokinetic/pharmacodynamic assessment of the effects of E4031, cisapride, terfenadine and terodiline on monophasic action potential duration in dog.
11569530	61	66	E4031	Chemical	C063968
11569530	68	77	cisapride	Chemical	D020117
11569530	79	90	terfenadine	Chemical	D016593
11569530	95	105	terodiline	Chemical	C010637
11569530	157	176	Torsades de pointes	Disease	D016171
11569530	178	181	TDP	Disease	D016171
11569530	206	229	ventricular tachycardia	Disease	D017180
11569530	320	323	TDP	Disease	D016171
11569530	407	418	terfenadine	Chemical	D016593
11569530	423	433	terodiline	Chemical	C010637
11569530	475	478	TDP	Disease	D016171
11569530	592	595	TDP	Disease	D016171
11569530	615	626	terfenadine	Chemical	D016593
11569530	628	638	terodiline	Chemical	C010637
11569530	640	649	cisapride	Chemical	D020117
11569530	654	659	E4031	Chemical	C063968
11569530	1142	1153	terfenadine	Chemical	D016593
11569530	1164	1174	terodiline	Chemical	C010637
11569530	1184	1193	cisapride	Chemical	D020117
11569530	1206	1211	E4031	Chemical	C063968
11569530	1324	1327	TDP	Disease	D016171
11569530	1343	1354	terfenadine	Chemical	D016593
11569530	1356	1366	terodiline	Chemical	C010637
11569530	1368	1377	cisapride	Chemical	D020117
11569530	1619	1622	TDP	Disease	D016171
11569530	Association	D016593	D016171
11569530	Association	C010637	D016171
11569530	Association	D020117	D016171
11569530	induced	D016593	D016171
11569530	induced	C010637	D016171
11569530	induced	D020117	D016171
11569530	induced	C063968	D016171
11569530	Association	C063968	D017180
11581460|a|Sedation has been commonly used in the neonate to decrease the stress and pain from the noxious stimuli and invasive procedures in the neonatal intensive care unit, as well as to facilitate synchrony between ventilator and spontaneous breaths. Fentanyl, an opioid analgesic, is frequently used in the neonatal intensive care unit setting for these very purposes. Various reported side effects of fentanyl administration include chest wall rigidity, hypotension, respiratory depression, and bradycardia. Here, 2 cases of urinary bladder retention leading to renal pelvocalyceal dilatation mimicking hydronephrosis as a result of continuous infusion of fentanyl are reported.
11581460|t|Bladder retention of urine as a result of continuous intravenous infusion of fentanyl: 2 case reports.
11581460	8	26	retention of urine	Disease	D016055
11581460	77	85	fentanyl	Chemical	D005283
11581460	177	181	pain	Disease	D010146
11581460	347	355	Fentanyl	Chemical	D005283
11581460	499	507	fentanyl	Chemical	D005283
11581460	531	550	chest wall rigidity	Disease	D009127
11581460	552	563	hypotension	Disease	D007022
11581460	565	587	respiratory depression	Disease	D012131
11581460	593	604	bradycardia	Disease	D001919
11581460	623	648	urinary bladder retention	Disease	D001745
11581460	701	715	hydronephrosis	Disease	D006869
11581460	754	762	fentanyl	Chemical	D005283
11581460	induced	D005283	D016055
11581460	Association	D005283	D006869
11581460	treated	D005283	D010146
11581460	induced	D005283	D009127
11581460	induced	D005283	D007022
11581460	induced	D005283	D012131
11581460	induced	D005283	D001919
11581460	induced	D005283	D001745
11642480|a|Current estimates suggest that between 0.4% and 8.3% of children and adolescents are affected by major depression. We report a favorable response to treatment with citalopram by a 15-year-old boy with major depression who exhibited palpebral twitching during his first 2 weeks of treatment. This may have been a side effect of citalopram as it remitted with redistribution of doses.
11642480|t|Palpebral twitching in a depressed adolescent on citalopram.
11642480	0	19	Palpebral twitching	Disease	D004409
11642480	25	34	depressed	Disease	D003866
11642480	49	59	citalopram	Chemical	D015283
11642480	158	174	major depression	Disease	D003865
11642480	225	235	citalopram	Chemical	D015283
11642480	262	278	major depression	Disease	D003865
11642480	293	312	palpebral twitching	Disease	D004409
11642480	388	398	citalopram	Chemical	D015283
11642480	induced	D015283	D004409
11642480	treated	D015283	D003866
11642480	treated	D015283	D003865
11679859|a|STUDY OBJECTIVE: We sought to compare the rate of akathisia after administration of intravenous prochlorperazine as a 2-minute bolus or 15-minute infusion. METHODS: We conducted a prospective, randomized, double-blind study in the emergency department of a central-city teaching hospital. Patients aged 18 years or older treated with prochlorperazine for headache, nausea, or vomiting were eligible for inclusion. Study participants were randomized to receive 10 mg of prochlorperazine administered intravenously by means of 2-minute push (bolus group) or 10 mg diluted in 50 mL of normal saline solution administered by means of intravenous infusion during a 15-minute period (infusion group). The main outcome was the number of study participants experiencing akathisia within 60 minutes of administration. Akathisia was defined as either a spontaneous report of restlessness or agitation or a change of 2 or more in the patient-reported akathisia rating scale and a change of at least 1 in the investigator-observed akathisia rating scale. The intensity of headache and nausea was measured with a 100-mm visual analog scale. RESULTS: One hundred patients were enrolled. One study participant was excluded after protocol violation. Seventy-three percent (73/99) of the study participants were treated for headache and 70% (70/99) for nausea. In the bolus group, 26.0% (13/50) had akathisia compared with 32.7% (16/49) in the infusion group (Delta=-6.7%; 95% confidence interval [CI] -24.6% to 11.2%). The difference between the bolus and infusion groups in the percentage of participants who saw a 50% reduction in their headache intensity within 30 minutes was 11.8% (95% CI -9.6% to 33.3%). The difference in the percentage of patients with a 50% reduction in their nausea was 12.6% (95% CI -4.6% to 29.8%). CONCLUSION: A 50% reduction in the incidence of akathisia when prochlorperazine was administered by means of 15-minute intravenous infusion versus a 2-minute intravenous push was not detected. The efficacy of prochlorperazine in the treatment of headache and nausea likewise did not appear to be affected by the rate of administration, although no formal statistical comparisons were made.
11679859|t|Intravenous administration of prochlorperazine by 15-minute infusion versus 2-minute bolus does not affect the incidence of akathisia: a prospective, randomized, controlled trial.
11679859	30	46	prochlorperazine	Chemical	D011346
11679859	124	133	akathisia	Disease	D017109
11679859	230	239	akathisia	Disease	D017109
11679859	276	292	prochlorperazine	Chemical	D011346
11679859	514	530	prochlorperazine	Chemical	D011346
11679859	535	543	headache	Disease	D006261
11679859	545	551	nausea	Disease	D009325
11679859	556	564	vomiting	Disease	D014839
11679859	649	665	prochlorperazine	Chemical	D011346
11679859	942	951	akathisia	Disease	D017109
11679859	1061	1070	agitation	Disease	D011595
11679859	1120	1129	akathisia	Disease	D017109
11679859	1199	1208	akathisia	Disease	D017109
11679859	1240	1248	headache	Disease	D006261
11679859	1253	1259	nausea	Disease	D009325
11679859	1487	1495	headache	Disease	D006261
11679859	1516	1522	nausea	Disease	D009325
11679859	1562	1571	akathisia	Disease	D017109
11679859	1803	1811	headache	Disease	D006261
11679859	1950	1956	nausea	Disease	D009325
11679859	2040	2049	akathisia	Disease	D017109
11679859	2055	2071	prochlorperazine	Chemical	D011346
11679859	2201	2217	prochlorperazine	Chemical	D011346
11679859	2238	2246	headache	Disease	D006261
11679859	2251	2257	nausea	Disease	D009325
11679859	Association	D011346	D011595
11679859	Association	D011346	D017109
11679859	treated	D011346	D006261
11679859	treated	D011346	D009325
11679859	treated	D011346	D014839
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|t|Tolerability of nimesulide and paracetamol in patients with NSAID-induced urticaria/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	treated	C012655	D014581
11694026	treated	D000082	D014581
11694026	treated	C012655	D000799
11694026	treated	D000082	D000799
11694026	induced	D000894	D014581
11694026	induced	D000894	D000799
11752354|a|BACKGROUND: An association between the use of oral contraceptives and the risk of myocardial infarction has been found in some, but not all, studies. We investigated this association, according to the type of progestagen included in third-generation (i.e., desogestrel or gestodene) and second-generation (i.e., levonorgestrel) oral contraceptives, the dose of estrogen, and the presence or absence of prothrombotic mutations METHODS: In a nationwide, population-based, case-control study, we identified and enrolled 248 women 18 through 49 years of age who had had a first myocardial infarction between 1990 and 1995 and 925 control women who had not had a myocardial infarction and who were matched for age, calendar year of the index event, and area of residence. Subjects supplied information on oral-contraceptive use and major cardiovascular risk factors. An analysis for factor V Leiden and the G20210A mutation in the prothrombin gene was conducted in 217 patients and 763 controls RESULTS: The odds ratio for myocardial infarction among women who used any type of combined oral contraceptive, as compared with nonusers, was 2.0 (95 percent confidence interval, 1.5 to 2.8). The adjusted odds ratio was 2.5 (95 percent confidence interval, 1.5 to 4.1) among women who used second-generation oral contraceptives and 1.3 (95 percent confidence interval, 0.7 to 2.5) among those who used third-generation oral contraceptives. Among women who used oral contraceptives, the odds ratio was 2.1 (95 percent confidence interval, 1.5 to 3.0) for those without a prothrombotic mutation and 1.9 (95 percent confidence interval, 0.6 to 5.5) for those with a mutation CONCLUSIONS: The risk of myocardial infarction was increased among women who used second-generation oral contraceptives. The results with respect to the use of third-generation oral contraceptives were inconclusive but suggested that the risk was lower than the risk associated with second-generation oral contraceptives. The risk of myocardial infarction was similar among women who used oral contraceptives whether or not they had a prothrombotic mutation.
11752354|t|Oral contraceptives and the risk of myocardial infarction.
11752354	0	19	Oral contraceptives	Chemical	D003276
11752354	36	57	myocardial infarction	Disease	D009203
11752354	105	124	oral contraceptives	Chemical	D003276
11752354	141	162	myocardial infarction	Disease	D009203
11752354	268	279	progestagen	Chemical	D011372
11752354	316	327	desogestrel	Chemical	D017135
11752354	331	340	gestodene	Chemical	C033273
11752354	371	385	levonorgestrel	Chemical	D016912
11752354	387	406	oral contraceptives	Chemical	D003276
11752354	420	428	estrogen	Chemical	D004967
11752354	633	654	myocardial infarction	Disease	D009203
11752354	717	738	myocardial infarction	Disease	D009203
11752354	859	877	oral-contraceptive	Chemical	D003276
11752354	1077	1098	myocardial infarction	Disease	D009203
11752354	1141	1159	oral contraceptive	Chemical	D003276
11752354	1358	1377	oral contraceptives	Chemical	D003276
11752354	1469	1488	oral contraceptives	Chemical	D003276
11752354	1511	1530	oral contraceptives	Chemical	D003276
11752354	1747	1768	myocardial infarction	Disease	D009203
11752354	1822	1841	oral contraceptives	Chemical	D003276
11752354	1899	1918	oral contraceptives	Chemical	D003276
11752354	2023	2042	oral contraceptives	Chemical	D003276
11752354	2056	2077	myocardial infarction	Disease	D009203
11752354	2111	2130	oral contraceptives	Chemical	D003276
11752354	induced	D003276	D009203
11752354	induced	D016912	D009203
11752354	Association	D011372	D009203
11752354	Association	D017135	D009203
11752354	Association	C033273	D009203
11752354	Association	D004967	D009203
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|t|Force overflow and levodopa-induced dyskinesias in Parkinson's disease.
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	induced	D007980	D004409
12041669|a|A patient who received antithymocyte globulin therapy for aplastic anemia due to D-penicillamine therapy is described. Bone marrow recovery and peripheral blood recovery were complete 1 month and 3 months, respectively, after treatment, and blood transfusion or other therapies were not necessary in a follow-up period of more than 2 years. Use of antithymocyte globulin may be the optimal treatment of D-penicillamine-induced aplastic anemia.
12041669|t|Antithymocyte globulin in the treatment of D-penicillamine-induced aplastic anemia.
12041669	0	22	Antithymocyte globulin	Chemical	D000961
12041669	43	58	D-penicillamine	Chemical	D010396
12041669	67	82	aplastic anemia	Disease	D000741
12041669	107	129	antithymocyte globulin	Chemical	D000961
12041669	142	157	aplastic anemia	Disease	D000741
12041669	165	180	D-penicillamine	Chemical	D010396
12041669	432	454	antithymocyte globulin	Chemical	D000961
12041669	487	502	D-penicillamine	Chemical	D010396
12041669	511	526	aplastic anemia	Disease	D000741
12041669	treated	D000961	D000741
12041669	induced	D010396	D000741
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|t|Topiramate-induced nephrolithiasis.
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	induced	C052342	D004827
12042105	induced	C052342	D000138
12042105	induced	C020243	D053040
12042105	induced	C052342	D053040
12084448|a|CNS toxic effects of the antineoplastic agent ifosfamide (IFX) are frequent and include a variety of neurological symptoms that can limit drug use. We report a case of a 51-year-old man who developed severe, disabling negative myoclonus of the upper and lower extremities after the infusion of ifosfamide for plasmacytoma. He was awake, revealed no changes of mental status and at rest there were no further motor symptoms. Cranial magnetic resonance imaging and extensive laboratory studies failed to reveal structural lesions of the brain and metabolic abnormalities. An electroencephalogram showed continuous, generalized irregular slowing with admixed periodic triphasic waves indicating symptomatic encephalopathy. The administration of ifosfamide was discontinued and within 12 h the asterixis resolved completely. In the patient described, the presence of asterixis during infusion of ifosfamide, normal laboratory findings and imaging studies and the resolution of symptoms following the discontinuation of the drug suggest that negative myoclonus is associated with the use of IFX.
12084448|t|Ifosfamide encephalopathy presenting with asterixis.
12084448	0	10	Ifosfamide	Chemical	D007069
12084448	11	25	encephalopathy	Disease	D001927
12084448	42	51	asterixis	Disease	D020820
12084448	99	109	ifosfamide	Chemical	D007069
12084448	111	114	IFX	Chemical	D007069
12084448	280	289	myoclonus	Disease	D009207
12084448	347	357	ifosfamide	Chemical	D007069
12084448	362	374	plasmacytoma	Disease	D010954
12084448	562	593	structural lesions of the brain	Disease	D001927
12084448	598	621	metabolic abnormalities	Disease	D008659
12084448	757	771	encephalopathy	Disease	D001927
12084448	795	805	ifosfamide	Chemical	D007069
12084448	843	852	asterixis	Disease	D020820
12084448	916	925	asterixis	Disease	D020820
12084448	945	955	ifosfamide	Chemical	D007069
12084448	1099	1108	myoclonus	Disease	D009207
12084448	1139	1142	IFX	Chemical	D007069
12084448	induced	D007069	D001927
12084448	induced	D007069	D020820
12084448	induced	D007069	D009207
12084448	treated	D007069	D010954
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|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	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	induced	D013806	D001167
12180796	induced	D018818	D001167
12180796	induced	D009569	D001167
12202650|a|The pathophysiology of painful temporomandibular disorders is not fully understood, but evidence suggests that muscle pain modulates motor function in characteristic ways. This study tested the hypothesis that activation of nociceptive muscle afferent fibers would be linked to an increased excitability of the human jaw-stretch reflex and whether this process would be sensitive to length and velocity of the stretch. Capsaicin (10 micro g) was injected into the masseter muscle to induce pain in 11 healthy volunteers. Short-latency reflex responses were evoked in the masseter and temporalis muscles by a stretch device with different velocities and displacements before, during, and after the pain. The normalized reflex amplitude increased with an increase in velocity at a given displacement, but remained constant with different displacements at a given velocity. The normalized reflex amplitude was significantly higher during pain, but only at faster stretches in the painful muscle. Increased sensitivity of the fusimotor system during acute muscle pain could be one likely mechanism to explain the findings.
12202650|t|Capsaicin-induced muscle pain alters the excitability of the human jaw-stretch reflex.
12202650	0	9	Capsaicin	Chemical	D002211
12202650	18	29	muscle pain	Disease	D063806
12202650	118	145	temporomandibular disorders	Disease	D013705
12202650	198	209	muscle pain	Disease	D063806
12202650	311	329	nociceptive muscle	Disease	D063806
12202650	506	515	Capsaicin	Chemical	D002211
12202650	577	581	pain	Disease	D010146
12202650	784	788	pain	Disease	D010146
12202650	1022	1026	pain	Disease	D010146
12202650	1064	1078	painful muscle	Disease	D063806
12202650	1139	1150	muscle pain	Disease	D063806
12202650	induced	D002211	D063806
12202650	induced	D002211	D010146
12369736|a|The present study was designed to examine the effect of 5-HT1B receptor ligands microinjected into the subregions of the nucleus accumbens (the shell and the core) on the locomotor hyperactivity induced by cocaine in rats. Male Wistar rats were implanted bilaterally with cannulae into the accumbens shell or core, and then were locally injected with GR 55562 (an antagonist of 5-HT1B receptors) or CP 93129 (an agonist of 5-HT1B receptors). Given alone to any accumbal subregion, GR 55562 (0.1-10 microg/side) or CP 93129 (0.1-10 microg/side) did not change basal locomotor activity. Systemic cocaine (10 mg/kg) significantly increased the locomotor activity of rats. GR 55562 (0.1-10 microg/side), administered intra-accumbens shell prior to cocaine, dose-dependently attenuated the psychostimulant-induced locomotor hyperactivity. Such attenuation was not found in animals which had been injected with GR 55562 into the accumbens core. When injected into the accumbens shell (but not the core) before cocaine, CP 93129 (0.1-10 microg/side) enhanced the locomotor response to cocaine; the maximum effect being observed after 10 microg/side of the agonist. The later enhancement was attenuated after intra-accumbens shell treatment with GR 55562 (1 microg/side). Our findings indicate that cocaine induced hyperlocomotion is modified by 5-HT1B receptor ligands microinjected into the accumbens shell, but not core, this modification consisting in inhibitory and facilitatory effects of the 5-HT1B receptor antagonist (GR 55562) and agonist (CP 93129), respectively. In other words, the present results suggest that the accumbal shell 5-HT1B receptors play a permissive role in the behavioural response to the psychostimulant.
12369736|t|Effects of 5-HT1B receptor ligands microinjected into the accumbal shell or core on the cocaine-induced locomotor hyperactivity in rats.
12369736	88	95	cocaine	Chemical	D003042
12369736	104	127	locomotor hyperactivity	Disease	D009069
12369736	308	331	locomotor hyperactivity	Disease	D009069
12369736	343	350	cocaine	Chemical	D003042
12369736	488	496	GR 55562	Chemical	C103477
12369736	536	544	CP 93129	Chemical	C065046
12369736	618	626	GR 55562	Chemical	C103477
12369736	651	659	CP 93129	Chemical	C065046
12369736	731	738	cocaine	Chemical	D003042
12369736	806	814	GR 55562	Chemical	C103477
12369736	881	888	cocaine	Chemical	D003042
12369736	946	969	locomotor hyperactivity	Disease	D009069
12369736	1042	1050	GR 55562	Chemical	C103477
12369736	1141	1148	cocaine	Chemical	D003042
12369736	1150	1158	CP 93129	Chemical	C065046
12369736	1215	1222	cocaine	Chemical	D003042
12369736	1375	1383	GR 55562	Chemical	C103477
12369736	1428	1435	cocaine	Chemical	D003042
12369736	1444	1459	hyperlocomotion	Disease	D009069
12369736	1656	1664	GR 55562	Chemical	C103477
12369736	1679	1687	CP 93129	Chemical	C065046
12369736	induced	D003042	D009069
12369736	treated	C103477	D009069
12369736	induced	C065046	D009069
12574103|a|Dexamethasone is frequently administered to the developing fetus to accelerate pulmonary development. The purpose of the present study was to determine if prenatal dexamethasone programmed a progressive increase in blood pressure and renal injury in rats. Pregnant rats were given either vehicle or 2 daily intraperitoneal injections of dexamethasone (0.2 mg/kg body weight) on gestational days 11 and 12, 13 and 14, 15 and 16, 17 and 18, or 19 and 20. Offspring of rats administered dexamethasone on days 15 and 16 gestation had a 20% reduction in glomerular number compared with control at 6 to 9 months of age (22 527+/-509 versus 28 050+/-561, P<0.05), which was comparable to the percent reduction in glomeruli measured at 3 weeks of age. Six- to 9-month old rats receiving prenatal dexamethasone on days 17 and 18 of gestation had a 17% reduction in glomeruli (23 380+/-587) compared with control rats (P<0.05). Male rats that received prenatal dexamethasone on days 15 and 16, 17 and 18, and 13 and 14 of gestation had elevated blood pressures at 6 months of age; the latter group did not have a reduction in glomerular number. Adult rats given dexamethasone on days 15 and 16 of gestation had more glomeruli with glomerulosclerosis than control rats. This study shows that prenatal dexamethasone in rats results in a reduction in glomerular number, glomerulosclerosis, and hypertension when administered at specific points during gestation. Hypertension was observed in animals that had a reduction in glomeruli as well as in a group that did not have a reduction in glomerular number, suggesting that a reduction in glomerular number is not the sole cause for the development of hypertension.
12574103|t|Prenatal dexamethasone programs hypertension and renal injury in the rat.
12574103	9	22	dexamethasone	Chemical	D003907
12574103	32	44	hypertension	Disease	D006973
12574103	49	61	renal injury	Disease	D007674
12574103	238	251	dexamethasone	Chemical	D003907
12574103	277	303	increase in blood pressure	Disease	D006973
12574103	308	320	renal injury	Disease	D007674
12574103	411	424	dexamethasone	Chemical	D003907
12574103	558	571	dexamethasone	Chemical	D003907
12574103	610	640	reduction in glomerular number	Disease	D007674
12574103	862	875	dexamethasone	Chemical	D003907
12574103	1025	1038	dexamethasone	Chemical	D003907
12574103	1100	1124	elevated blood pressures	Disease	D006973
12574103	1177	1207	reduction in glomerular number	Disease	D007674
12574103	1226	1239	dexamethasone	Chemical	D003907
12574103	1295	1313	glomerulosclerosis	Disease	D005921
12574103	1364	1377	dexamethasone	Chemical	D003907
12574103	1399	1429	reduction in glomerular number	Disease	D007674
12574103	1431	1449	glomerulosclerosis	Disease	D005921
12574103	1455	1467	hypertension	Disease	D006973
12574103	1523	1535	Hypertension	Disease	D006973
12574103	1636	1666	reduction in glomerular number	Disease	D007674
12574103	1686	1716	reduction in glomerular number	Disease	D007674
12574103	1762	1774	hypertension	Disease	D006973
12574103	induced	D003907	D005921
12574103	induced	D003907	D006973
12574103	induced	D003907	D007674
12615818|a|BACKGROUND: Cyproterone acetate combined with ethinyl estradiol (CPA/EE) is licensed in the UK for the treatment of women with acne and hirsutism and is also a treatment option for polycystic ovary syndrome (PCOS). Previous studies have demonstrated an increased risk of venous thromboembolism (VTE) associated with CPA/EE compared with conventional combined oral contraceptives (COCs). We believe the results of those studies may have been affected by residual confounding. METHODS: Using the General Practice Research Database we conducted a cohort analysis and case-control study nested within a population of women aged between 15 and 39 years with acne, hirsutism or PCOS to estimate the risk of VTE associated with CPA/EE. RESULTS: The age-adjusted incidence rate ratio for CPA/EE versus conventional COCs was 2.20 [95% confidence interval (CI) 1.35-3.58]. Using as the reference group women who were not using oral contraception, had no recent pregnancy or menopausal symptoms, the case-control analysis gave an adjusted odds ratio (OR(adj)) of 7.44 (95% CI 3.67-15.08) for CPA/EE use compared with an OR(adj) of 2.58 (95% CI 1.60-4.18) for use of conventional COCs. CONCLUSIONS: We have demonstrated an increased risk of VTE associated with the use of CPA/EE in women with acne, hirsutism or PCOS although residual confounding by indication cannot be excluded.
12615818|t|The risk of venous thromboembolism in women prescribed cyproterone acetate in combination with ethinyl estradiol: a nested cohort analysis and case-control study.
12615818	12	34	venous thromboembolism	Disease	D054556
12615818	55	74	cyproterone acetate	Chemical	D017373
12615818	95	112	ethinyl estradiol	Chemical	D004997
12615818	175	194	Cyproterone acetate	Chemical	D017373
12615818	209	226	ethinyl estradiol	Chemical	D004997
12615818	228	231	CPA	Chemical	D017373
12615818	232	234	EE	Chemical	D004997
12615818	290	294	acne	Disease	D000152
12615818	299	308	hirsutism	Disease	D006628
12615818	344	369	polycystic ovary syndrome	Disease	D011085
12615818	371	375	PCOS	Disease	D011085
12615818	434	456	venous thromboembolism	Disease	D054556
12615818	458	461	VTE	Disease	D054556
12615818	479	482	CPA	Chemical	D017373
12615818	483	485	EE	Chemical	D004997
12615818	522	541	oral contraceptives	Chemical	D003276
12615818	816	820	acne	Disease	D000152
12615818	822	831	hirsutism	Disease	D006628
12615818	835	839	PCOS	Disease	D011085
12615818	864	867	VTE	Disease	D054556
12615818	884	887	CPA	Chemical	D017373
12615818	888	890	EE	Chemical	D004997
12615818	943	946	CPA	Chemical	D017373
12615818	947	949	EE	Chemical	D004997
12615818	1244	1247	CPA	Chemical	D017373
12615818	1248	1250	EE	Chemical	D004997
12615818	1392	1395	VTE	Disease	D054556
12615818	1423	1426	CPA	Chemical	D017373
12615818	1427	1429	EE	Chemical	D004997
12615818	1444	1448	acne	Disease	D000152
12615818	1450	1459	hirsutism	Disease	D006628
12615818	1463	1467	PCOS	Disease	D011085
12615818	induced	D017373	D054556
12615818	induced	D003276	D054556
12615818	induced	D004997	D054556
12615818	treated	D003276	D000152
12615818	treated	D003276	D006628
12615818	treated	D003276	D011085
12615818	treated	D017373	D000152
12615818	treated	D017373	D006628
12615818	treated	D017373	D011085
12615818	treated	D004997	D000152
12615818	treated	D004997	D006628
12615818	treated	D004997	D011085
12639165|a|OBJECTIVE: To report 2 cases of ticlopidine-induced cholestatic hepatitis, investigate its mechanism, and compare the observed main characteristics with those of the published cases. CASE SUMMARIES: Two patients developed prolonged cholestatic hepatitis after receiving ticlopidine following percutaneous coronary angioplasty, with complete remission during the follow-up period. T-cell stimulation by therapeutic concentration of ticlopidine was demonstrated in vitro in the patients, but not in healthy controls. DISCUSSION: Cholestatic hepatitis is a rare complication of the antiplatelet agent ticlopidine; several cases have been reported but few in the English literature. Our patients developed jaundice following treatment with ticlopidine and showed the clinical and laboratory characteristics of cholestatic hepatitis, which resolved after discontinuation of the drug. Hepatitis may develop weeks after discontinuation of the drug and may run a prolonged course, but complete remission was observed in all reported cases. An objective causality assessment revealed that the adverse drug event was probably related to the use of ticlopidine. The mechanisms of this ticlopidine-induced cholestasis are unclear. Immune mechanisms may be involved in the drug's hepatotoxicity, as suggested by the T-cell stimulation study reported here. CONCLUSIONS: Cholestatic hepatitis is a rare adverse effect of ticlopidine that may be immune mediated. Patients receiving the drug should be monitored with liver function tests along with complete blood cell counts. This complication will be observed even less often in the future as ticlopidine is being replaced by the newer antiplatelet agent clopidogrel.
12639165|t|Ticlopidine-induced cholestatic hepatitis.
12639165	0	11	Ticlopidine	Chemical	D013988
12639165	20	31	cholestatic	Disease	D002779
12639165	32	41	hepatitis	Disease	D056486
12639165	75	86	ticlopidine	Chemical	D013988
12639165	95	116	cholestatic hepatitis	Chemical	-1
12639165	95	106	cholestatic	Disease	D002779
12639165	107	116	hepatitis	Disease	D056486
12639165	275	286	cholestatic	Disease	D002779
12639165	287	296	hepatitis	Disease	D056486
12639165	313	324	ticlopidine	Chemical	D013988
12639165	474	485	ticlopidine	Chemical	D013988
12639165	570	581	Cholestatic	Disease	D002779
12639165	582	591	hepatitis	Disease	D056486
12639165	641	652	ticlopidine	Chemical	D013988
12639165	745	753	jaundice	Disease	D007565
12639165	779	790	ticlopidine	Chemical	D013988
12639165	849	860	cholestatic	Disease	D002779
12639165	861	870	hepatitis	Disease	D056486
12639165	922	931	Hepatitis	Disease	D056486
12639165	1181	1192	ticlopidine	Chemical	D013988
12639165	1217	1228	ticlopidine	Chemical	D013988
12639165	1237	1248	cholestasis	Disease	D002779
12639165	1310	1324	hepatotoxicity	Disease	D056486
12639165	1399	1410	Cholestatic	Disease	D002779
12639165	1411	1420	hepatitis	Disease	D056486
12639165	1449	1460	ticlopidine	Chemical	D013988
12639165	1671	1682	ticlopidine	Chemical	D013988
12639165	1733	1744	clopidogrel	Chemical	C055162
12639165	induced	D013988	D002779
12639165	induced	D013988	D056486
12639165	induced	D013988	D007565
12639165	induced	D013988	-1
12653683|a|In experimental nephrotic syndrome, urinary sodium excretion is decreased during the early phase of the disease. The molecular mechanism(s) leading to salt retention has not been completely elucidated. The rate-limiting constituent of collecting duct sodium transport is the epithelial sodium channel (ENaC). We examined the abundance of ENaC subunit mRNAs and proteins in puromycin aminonucleoside (PAN)-induced nephrotic syndrome. The time courses of urinary sodium excretion, plasma aldosterone concentration and proteinuria were studied in male Sprague-Dawley rats treated with a single dose of either PAN or vehicle. The relative amounts of alphaENaC, betaENaC and gammaENaC mRNAs were determined in kidneys from these rats by real-time quantitative TaqMan PCR, and the amounts of proteins by Western blot. The kinetics of urinary sodium excretion and the appearance of proteinuria were comparable with those reported previously. Sodium retention occurred on days 2, 3 and 6 after PAN injection. A significant up-regulation of alphaENaC and betaENaC mRNA abundance on days 1 and 2 preceded sodium retention on days 2 and 3. Conversely, down-regulation of alphaENaC, betaENaC and gammaENaC mRNA expression on day 3 occurred in the presence of high aldosterone concentrations, and was followed by a return of sodium excretion to control values. The amounts of alphaENaC, betaENaC and gammaENaC proteins were not increased during PAN-induced sodium retention. In conclusion, ENaC mRNA expression, especially alphaENaC, is increased in the very early phase of the experimental model of PAN-induced nephrotic syndrome in rats, but appears to escape from the regulation by aldosterone after day 3.
12653683|t|Epithelial sodium channel (ENaC) subunit mRNA and protein expression in rats with puromycin aminonucleoside-induced nephrotic syndrome.
12653683	11	17	sodium	Chemical	D012964
12653683	82	107	puromycin aminonucleoside	Chemical	D011692
12653683	116	134	nephrotic syndrome	Disease	D009404
12653683	152	170	nephrotic syndrome	Disease	D009404
12653683	180	186	sodium	Chemical	D012964
12653683	387	393	sodium	Chemical	D012964
12653683	422	428	sodium	Chemical	D012964
12653683	509	534	puromycin aminonucleoside	Chemical	D011692
12653683	536	539	PAN	Chemical	D011692
12653683	549	567	nephrotic syndrome	Disease	D009404
12653683	597	603	sodium	Chemical	D012964
12653683	622	633	aldosterone	Chemical	D000450
12653683	652	663	proteinuria	Disease	D011507
12653683	742	745	PAN	Chemical	D011692
12653683	972	978	sodium	Chemical	D012964
12653683	1011	1022	proteinuria	Disease	D011507
12653683	1071	1077	Sodium	Chemical	D012964
12653683	1122	1125	PAN	Chemical	D011692
12653683	1231	1237	sodium	Chemical	D012964
12653683	1388	1399	aldosterone	Chemical	D000450
12653683	1448	1454	sodium	Chemical	D012964
12653683	1568	1571	PAN	Chemical	D011692
12653683	1580	1586	sodium	Chemical	D012964
12653683	1723	1726	PAN	Chemical	D011692
12653683	1735	1753	nephrotic syndrome	Disease	D009404
12653683	1808	1819	aldosterone	Chemical	D000450
12653683	induced	D012964	D009404
12653683	induced	D011692	D009404
12716030|a|The aggravated risk on intracerebral hemorrhage (ICH) with drugs used for stroke patients should be estimated carefully. We therefore established sensitive quantification methods and provided a rat ICH model for detection of ICH deterioration. In ICH intrastriatally induced by 0.014-unit, 0.070-unit, and 0.350-unit collagenase, the amount of bleeding was measured using a hemoglobin assay developed in the present study and was compared with the morphologically determined hematoma volume. The blood amounts and hematoma volumes were significantly correlated, and the hematoma induced by 0.014-unit collagenase was adequate to detect ICH deterioration. In ICH induction using 0.014-unit collagenase, heparin enhanced the hematoma volume 3.4-fold over that seen in control ICH animals and the bleeding 7.6-fold. Data suggest that this sensitive hemoglobin assay is useful for ICH detection, and that a model with a small ICH induced with a low-dose collagenase should be used for evaluation of drugs that may affect ICH.
12716030|t|Amount of bleeding and hematoma size in the collagenase-induced intracerebral hemorrhage rat model.
12716030	10	18	bleeding	Disease	D006470
12716030	23	31	hematoma	Disease	D006406
12716030	64	88	intracerebral hemorrhage	Disease	D002543
12716030	123	147	intracerebral hemorrhage	Disease	D002543
12716030	149	152	ICH	Disease	D002543
12716030	174	180	stroke	Disease	D020521
12716030	298	301	ICH	Disease	D002543
12716030	325	328	ICH	Disease	D002543
12716030	347	350	ICH	Disease	D002543
12716030	444	452	bleeding	Disease	D006470
12716030	575	583	hematoma	Disease	D006406
12716030	614	622	hematoma	Disease	D006406
12716030	670	678	hematoma	Disease	D006406
12716030	736	739	ICH	Disease	D002543
12716030	758	761	ICH	Disease	D002543
12716030	802	809	heparin	Chemical	D006493
12716030	823	831	hematoma	Disease	D006406
12716030	874	877	ICH	Disease	D002543
12716030	894	902	bleeding	Disease	D006470
12716030	977	980	ICH	Disease	D002543
12716030	1022	1025	ICH	Disease	D002543
12716030	1117	1120	ICH	Disease	D002543
12716030	induced	D006493	D006406
12716030	induced	D006493	D002543
12716030	induced	D006493	D006470
12716030	treated	D006493	D020521
12789195|a|Acromegaly is an endocrine disorder caused by chronic excessive growth hormone secretion from the anterior pituitary gland. Significant disfiguring changes occur as a result of bone, cartilage, and soft tissue hypertrophy, including the thickening of the skin, coarsening of facial features, and cutis verticis gyrata. Pseudoacromegaly, on the other hand, is the presence of similar acromegaloid features in the absence of elevated growth hormone or insulin-like growth factor levels. We present a patient with pseudoacromegaly that resulted from the long-term use of minoxidil at an unusually high dose. This is the first case report of pseudoacromegaly as a side effect of minoxidil use.
12789195|t|Pseudoacromegaly induced by the long-term use of minoxidil.
12789195	0	16	Pseudoacromegaly	Disease	D004194
12789195	49	58	minoxidil	Chemical	D008914
12789195	60	70	Acromegaly	Disease	D000172
12789195	77	95	endocrine disorder	Disease	D004700
12789195	270	281	hypertrophy	Disease	D006984
12789195	356	377	cutis verticis gyrata	Disease	C535610
12789195	379	395	Pseudoacromegaly	Disease	D004194
12789195	571	587	pseudoacromegaly	Disease	D004194
12789195	628	637	minoxidil	Chemical	D008914
12789195	698	714	pseudoacromegaly	Disease	D004194
12789195	735	744	minoxidil	Chemical	D008914
12789195	induced	D008914	C535610
12789195	induced	D008914	D006984
12789195	induced	D008914	D004194
12905102|a|BACKGROUND: Incidence and risk factors for delirium during clozapine treatment require further clarification. METHODS: We used computerized pharmacy records to identify all adult psychiatric inpatients treated with clozapine (1995-96), reviewed their medical records to score incidence and severity of delirium, and tested associations with potential risk factors. RESULTS: Subjects (n = 139) were 72 women and 67 men, aged 40.8 +/- 12.1 years, hospitalized for 24.9 +/- 23.3 days, and given clozapine, gradually increased to an average daily dose of 282 +/- 203 mg (3.45 +/- 2.45 mg/kg) for 18.9 +/- 16.4 days. Delirium was diagnosed in 14 (10.1 % incidence, or 1.48 cases/person-years of exposure); 71.4 % of cases were moderate or severe. Associated factors were co-treatment with other centrally antimuscarinic agents, poor clinical outcome, older age, and longer hospitalization (by 17.5 days, increasing cost); sex, diagnosis or medical co-morbidity, and daily clozapine dose, which fell with age, were unrelated. CONCLUSIONS: Delirium was found in 10 % of clozapine-treated inpatients, particularly in older patients exposed to other central anticholinergics. Delirium was inconsistently recognized clinically in milder cases and was associated with increased length-of-stay and higher costs, and inferior clinical outcome.
12905102|t|Delirium during clozapine treatment: incidence and associated risk factors.
12905102	0	8	Delirium	Disease	D003693
12905102	16	25	clozapine	Chemical	D003024
12905102	119	127	delirium	Disease	D003693
12905102	135	144	clozapine	Chemical	D003024
12905102	255	266	psychiatric	Disease	D001523
12905102	291	300	clozapine	Chemical	D003024
12905102	378	386	delirium	Disease	D003693
12905102	568	577	clozapine	Chemical	D003024
12905102	688	696	Delirium	Disease	D003693
12905102	1043	1052	clozapine	Chemical	D003024
12905102	1109	1117	Delirium	Disease	D003693
12905102	1139	1148	clozapine	Chemical	D003024
12905102	1243	1251	Delirium	Disease	D003693
12905102	induced	D003024	D003693
1378968|a|Rats with lithium-induced nephropathy were subjected to high protein (HP) feeding, uninephrectomy (NX) or a combination of these, in an attempt to induce glomerular hyperfiltration and further progression of renal failure. Newborn female Wistar rats were fed a lithium-containing diet (50 mmol/kg) for 8 weeks and then randomized to normal diet, HP diet (40 vs. 19%), NX or HP+NX for another 8 weeks. Corresponding non-lithium pretreated groups were generated. When comparing all lithium treated versus non-lithium-treated groups, lithium caused a reduction in glomerular filtration rate (GFR) without significant changes in effective renal plasma flow (as determined by a marker secreted into the proximal tubules) or lithium clearance. Consequently, lithium pretreatment caused a fall in filtration fraction and an increase in fractional Li excretion. Lithium also caused proteinuria and systolic hypertension in absence of glomerulosclerosis. HP failed to accentuante progression of renal failure and in fact tended to increase GFR and decrease plasma creatinine levels in lithium pretreated rats. NX caused an additive deterioration in GFR which, however, was ameliorated by HP. NX+HP caused a further rise in blood pressure in Li-pretreated rats. The results indicate that Li-induced nephropathy, even when the GFR is only modestly reduced, is associated with proteinuria and arterial systolic hypertension. In this model of chronic renal failure the decline in GFR is not accompanied by a corresponding fall in effective renal plasma flow, which may be the functional expression of the formation of nonfiltrating atubular glomeruli. The fractional reabsorption of tubular fluid by the proximal tubules is reduced, leaving the distal delivery unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
1378968|t|Effects of uninephrectomy and high protein feeding on lithium-induced chronic renal failure in rats.
1378968	54	61	lithium	Chemical	D008094
1378968	70	91	chronic renal failure	Disease	D007676
1378968	111	118	lithium	Chemical	D008094
1378968	127	138	nephropathy	Disease	D007674
1378968	309	322	renal failure	Disease	D051437
1378968	362	369	lithium	Chemical	D008094
1378968	520	527	lithium	Chemical	D008094
1378968	581	588	lithium	Chemical	D008094
1378968	608	615	lithium	Chemical	D008094
1378968	632	639	lithium	Chemical	D008094
1378968	820	827	lithium	Chemical	D008094
1378968	853	860	lithium	Chemical	D008094
1378968	941	943	Li	Chemical	D008094
1378968	955	962	Lithium	Chemical	D008094
1378968	975	986	proteinuria	Disease	D011507
1378968	1000	1012	hypertension	Disease	D006973
1378968	1027	1045	glomerulosclerosis	Disease	D005921
1378968	1087	1100	renal failure	Disease	D051437
1378968	1156	1166	creatinine	Chemical	D003404
1378968	1177	1184	lithium	Chemical	D008094
1378968	1333	1335	Li	Chemical	D008094
1378968	1379	1381	Li	Chemical	D008094
1378968	1390	1401	nephropathy	Disease	D007674
1378968	1466	1477	proteinuria	Disease	D011507
1378968	1500	1512	hypertension	Disease	D006973
1378968	1531	1552	chronic renal failure	Disease	D007676
1378968	induced	D008094	D007676
1378968	induced	D008094	D011507
1378968	induced	D008094	D006973
1378968	Association	D003404	D051437
1378968	Association	D003404	D007674
1378968	Association	D003404	D011507
1378968	Association	D003404	D006973
1378968	Association	D003404	D007676
1378968	induced	D008094	D007674
1378968	induced	D008094	D051437
1420741|a|Fusidic acid is an antibiotic with T-cell specific immunosuppressive effects similar to those of cyclosporin. Because of the need for the development of new treatments for Crohn's disease, a pilot study was undertaken to estimate the pharmacodynamics and tolerability of fusidic acid treatment in chronic active, therapy-resistant patients. Eight Crohn's disease patients were included. Fusidic acid was administered orally in a dose of 500 mg t.d.s. and the treatment was planned to last 8 weeks. The disease activity was primarily measured by a modified individual grading score. Five of 8 patients (63%) improved during fusidic acid treatment: 3 at two weeks and 2 after four weeks. There were no serious clinical side effects, but dose reduction was required in two patients because of nausea. Biochemically, an increase in alkaline phosphatases was noted in 5 of 8 cases (63%), and the greatest increases were seen in those who had elevated levels prior to treatment. All reversed to pre-treatment levels after cessation of treatment. The results of this pilot study suggest that fusidic acid may be of benefit in selected chronic active Crohn's disease patients in whom conventional treatment is ineffective. Because there seems to exist a scientific rationale for the use of fusidic acid at the cytokine level in inflammatory bowel disease, we suggest that the role of this treatment should be further investigated.
1420741|t|Treatment of Crohn's disease with fusidic acid: an antibiotic with immunosuppressive properties similar to cyclosporin.
1420741	13	28	Crohn's disease	Disease	D003424
1420741	34	46	fusidic acid	Chemical	D005672
1420741	107	118	cyclosporin	Chemical	D016572
1420741	217	228	cyclosporin	Chemical	D016572
1420741	292	307	Crohn's disease	Disease	D003424
1420741	391	403	fusidic acid	Chemical	D005672
1420741	467	482	Crohn's disease	Disease	D003424
1420741	507	519	Fusidic acid	Chemical	D005672
1420741	743	755	fusidic acid	Chemical	D005672
1420741	910	916	nausea	Disease	D009325
1420741	1205	1217	fusidic acid	Chemical	D005672
1420741	1263	1278	Crohn's disease	Disease	D003424
1420741	1402	1414	fusidic acid	Chemical	D005672
1420741	1440	1466	inflammatory bowel disease	Disease	D015212
1420741	treated	D005672	D003424
1420741	Association	D016572	D003424
1420741	treated	D005672	D015212
1420741	Association	D016572	D015212
1420741	induced	D005672	D009325
1428568|a|Depression and sexual dysfunction have been related to side effects of topical beta-blockers. We performed a preliminary study in order to determine any difference between a non selective beta-blocker (timolol) and a selective beta-blocker (betaxolol) regarding CNS side effects. Eight glaucomatous patients chronically treated with timolol 0.5%/12h, suffering from depression diagnosed through DMS-III-R criteria, were included in the study. During the six-month follow up, depression was quantified through the Beck and Zung-Conde scales every two months. In a double blind cross-over study with control group, the patients under timolol treatment presented higher depression values measured through the Beck and the Zung-Conde scales (p < 0.001 vs control). These results suggest that betaxolol could be less of a depression-inducer than timolol in predisposed patients.
1428568|t|Changes in depressive status associated with topical beta-blockers.
1428568	11	21	depressive	Disease	D003866
1428568	68	78	Depression	Disease	D003866
1428568	83	101	sexual dysfunction	Disease	D012735
1428568	270	277	timolol	Chemical	D013999
1428568	309	318	betaxolol	Chemical	D015784
1428568	354	366	glaucomatous	Disease	D005901
1428568	401	408	timolol	Chemical	D013999
1428568	434	444	depression	Disease	D003866
1428568	543	553	depression	Disease	D003866
1428568	700	707	timolol	Chemical	D013999
1428568	735	745	depression	Disease	D003866
1428568	856	865	betaxolol	Chemical	D015784
1428568	885	895	depression	Disease	D003866
1428568	909	916	timolol	Chemical	D013999
1428568	induced	D013999	D003866
14513889|a|A 77-y-old patient developed weakness of extremities, legs paralysis, dysarthria and tremor 1 h after ingestion of 200 mg ketoconazole for the first time in his life. All complaints faded away within 24 h. Few days later, the patient used another 200 mg ketoconazole tablet, and within an hour experienced a similar clinical picture, which resolved again spontaneously within hours. Laboratory evaluations, including head CT scan, were normal. This case illustrates the need for close vigilance in adverse drug reactions, particularly in the elderly.
14513889|t|Ketoconazole-induced neurologic sequelae.
14513889	0	12	Ketoconazole	Chemical	D007654
14513889	21	40	neurologic sequelae	Disease	D009422
14513889	71	94	weakness of extremities	Disease	D018908
14513889	96	110	legs paralysis	Disease	D010243
14513889	112	122	dysarthria	Disease	D004401
14513889	127	133	tremor	Disease	D014202
14513889	164	176	ketoconazole	Chemical	D007654
14513889	296	308	ketoconazole	Chemical	D007654
14513889	540	562	adverse drug reactions	Disease	D064420
14513889	induced	D007654	D009422
14513889	induced	D007654	D018908
14513889	induced	D007654	D010243
14513889	induced	D007654	D004401
14513889	induced	D007654	D014202
14657095|a|We describe a patient who developed dilated cardiomyopathy and clinical congestive heart failure after 2 months of therapy with amphotericin B (AmB) for disseminated coccidioidomycosis. His echocardiographic abnormalities and heart failure resolved after posaconazole was substituted for AmB. It is important to recognize the rare and potentially reversible toxicity of AmB.
14657095|t|Reversible dilated cardiomyopathy related to amphotericin B therapy.
14657095	11	33	dilated cardiomyopathy	Disease	D002311
14657095	45	59	amphotericin B	Chemical	D000666
14657095	105	127	dilated cardiomyopathy	Disease	D002311
14657095	152	165	heart failure	Disease	D006333
14657095	197	211	amphotericin B	Chemical	D000666
14657095	213	216	AmB	Chemical	D000666
14657095	235	253	coccidioidomycosis	Disease	D003047
14657095	295	308	heart failure	Disease	D006333
14657095	324	336	posaconazole	Chemical	C101425
14657095	357	360	AmB	Chemical	D000666
14657095	427	435	toxicity	Disease	D064420
14657095	439	442	AmB	Chemical	D000666
14657095	induced	D000666	D064420
14657095	induced	D000666	D002311
14657095	treated	C101425	D002311
14657095	induced	D000666	D006333
14657095	treated	D000666	D003047
14657095	treated	C101425	D003047
14657095	treated	C101425	D006333
14765563|a|Although the United States Food and Drug Administration banned its use for nocturnal leg cramps due to lack of safety and efficacy, quinine is widely available in beverages including tonic water and bitter lemon. Numerous anecdotal reports suggest that products containing quinine may produce neurological complications, including confusion, altered mental status, seizures, and coma, particularly in older women. Psychologists need to inquire about consumption of quinine-containing beverages as part of an evaluation process.
14765563|t|Risks of the consumption of beverages containing quinine.
14765563	49	56	quinine	Chemical	D011803
14765563	133	153	nocturnal leg cramps	Disease	D020922
14765563	190	197	quinine	Chemical	D011803
14765563	331	338	quinine	Chemical	D011803
14765563	351	377	neurological complications	Disease	D002493
14765563	389	398	confusion	Disease	D003221
14765563	423	431	seizures	Disease	D012640
14765563	437	441	coma	Disease	D003128
14765563	523	530	quinine	Chemical	D011803
14765563	treated	D011803	D020922
14765563	induced	D011803	D002493
14765563	induced	D011803	D003221
14765563	induced	D011803	D012640
14765563	induced	D011803	D003128
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|t|Expression of p300 protects cardiac myocytes from apoptosis 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	treated	D004317	D009369
14975762	induced	D004317	D006333
15120741|a|Similar to rats, systemic pilocarpine injection causes status epilepticus (SE) and the eventual development of spontaneous seizures and mossy fiber sprouting in C57BL/6 and CD1 mice, but the physiological correlates of these events have not been identified in mice. Population responses in granule cells of the dentate gyrus were examined in transverse slices of the ventral hippocampus from pilocarpine-treated and untreated mice. In Mg(2+)-free bathing medium containing bicuculline, conditions designed to increase excitability in the slices, electrical stimulation of the hilus resulted in a single population spike in granule cells from control mice and pilocarpine-treated mice that did not experience SE. In SE survivors, similar stimulation resulted in a population spike followed, at a variable latency, by negative DC shifts and repetitive afterdischarges of 3-60 s duration, which were blocked by ionotropic glutamate receptor antagonists. Focal glutamate photostimulation of the granule cell layer at sites distant from the recording pipette resulted in population responses of 1-30 s duration in slices from SE survivors but not other groups. These data support the hypothesis that SE-induced mossy fiber sprouting and synaptic reorganization are relevant characteristics of seizure development in these murine strains, resembling rat models of human temporal lobe epilepsy.
15120741|t|Recurrent excitation in the dentate gyrus of a murine model of temporal lobe epilepsy.
15120741	63	85	temporal lobe epilepsy	Disease	D004833
15120741	113	124	pilocarpine	Chemical	D010862
15120741	142	160	status epilepticus	Disease	D013226
15120741	162	164	SE	Disease	D013226
15120741	210	218	seizures	Disease	D012640
15120741	479	490	pilocarpine	Chemical	D010862
15120741	522	524	Mg	Chemical	D008274
15120741	560	571	bicuculline	Chemical	D001640
15120741	746	757	pilocarpine	Chemical	D010862
15120741	795	797	SE	Disease	D013226
15120741	802	804	SE	Disease	D013226
15120741	1006	1015	glutamate	Chemical	D018698
15120741	1044	1053	glutamate	Chemical	D018698
15120741	1208	1210	SE	Disease	D013226
15120741	1282	1284	SE	Disease	D013226
15120741	1375	1382	seizure	Disease	D012640
15120741	1451	1473	temporal lobe epilepsy	Disease	D004833
15120741	induced	D010862	D013226
15120741	induced	D010862	D012640
15120741	induced	D018698	D012640
15233872|a|Tincture of Crataegus (TCR), an alcoholic extract of the berries of hawthorn (Crataegus oxycantha), is used in herbal and homeopathic medicine. The present study was done to investigate the protective effect of TCR on experimentally induced myocardial infarction in rats. Pretreatment of TCR, at a dose of 0.5 mL/100 g bodyweight per day, orally for 30 days, prevented the increase in lipid peroxidation and activity of marker enzymes observed in isoproterenol-induced rats (85 mg kg(-1) s. c. for 2 days at an interval of 24 h). TCR prevented the isoproterenol-induced decrease in antioxidant enzymes in the heart and increased the rate of ADP-stimulated oxygen uptake and respiratory coupling ratio. TCR protected against pathological changes induced by isoproterenol in rat heart. The results show that pretreatment with TCR may be useful in preventing the damage induced by isoproterenol in rat heart.
15233872|t|Cardioprotective effect of tincture of Crataegus on isoproterenol-induced myocardial infarction in rats.
15233872	27	48	tincture of Crataegus	Chemical	C007145
15233872	52	65	isoproterenol	Chemical	D007545
15233872	74	95	myocardial infarction	Disease	D009203
15233872	105	126	Tincture of Crataegus	Chemical	C007145
15233872	128	131	TCR	Chemical	C007145
15233872	137	181	alcoholic extract of the berries of hawthorn	Chemical	C007145
15233872	183	202	Crataegus oxycantha	Chemical	C007145
15233872	316	319	TCR	Chemical	C007145
15233872	346	367	myocardial infarction	Disease	D009203
15233872	393	396	TCR	Chemical	C007145
15233872	552	565	isoproterenol	Chemical	D007545
15233872	635	638	TCR	Chemical	C007145
15233872	653	666	isoproterenol	Chemical	D007545
15233872	746	749	ADP	Chemical	D000244
15233872	761	767	oxygen	Chemical	D010100
15233872	807	810	TCR	Chemical	C007145
15233872	861	874	isoproterenol	Chemical	D007545
15233872	929	932	TCR	Chemical	C007145
15233872	983	996	isoproterenol	Chemical	D007545
15233872	induced	D007545	D009203
15233872	Association	D000244	D009203
15233872	Association	D010100	D009203
15233872	treated	C007145	D009203
15602202|a|A 14-year-old girl is reported with recurrent, azithromycin-induced, acute interstitial nephritis. The second episode was more severe than the first; and although both were treated with intensive corticosteroid therapy, renal function remained impaired. Although most cases of antibiotic induced acute interstitial nephritis are benign and self-limited, some patients are at risk for permanent renal injury.
15602202|t|Recurrent acute interstitial nephritis induced by azithromycin.
15602202	16	38	interstitial nephritis	Disease	D009395
15602202	50	62	azithromycin	Chemical	D017963
15602202	111	123	azithromycin	Chemical	D017963
15602202	139	161	interstitial nephritis	Disease	D009395
15602202	366	388	interstitial nephritis	Disease	D009395
15602202	458	470	renal injury	Disease	D007674
15602202	induced	D017963	D009395
15602202	induced	D017963	D007674
15737522|a|It is well known that ceftriaxone leads to pseudolithiasis in some patients. Clinical and experimental studies also suggest that situations causing gallbladder dysfunction, such as fasting, may have a role for the development of pseudolithiasis. In this study, we prospectively evaluated the incidence and clinical importance of pseudolithiasis in paediatric surgical patients receiving ceftriaxone treatment, who often had to fast in the post-operative period. Fifty children who were given ceftriaxone were evaluated by serial abdominal sonograms. Of those, 13 (26%) developed biliary pathology. Comparison of the patients with or without pseudolithiasis revealed no significant difference with respect to age, sex, duration of the treatment and starvation variables. After cessation of the treatment, pseudolithiasis resolved spontaneously within a short period. The incidence of pseudolithiasis is not affected by fasting.
15737522|t|Ceftriaxone-associated biliary pseudolithiasis in paediatric surgical patients.
15737522	0	11	Ceftriaxone	Chemical	D002443
15737522	23	46	biliary pseudolithiasis	Disease	D001660
15737522	102	113	ceftriaxone	Chemical	D002443
15737522	123	138	pseudolithiasis	Disease	D001660
15737522	228	251	gallbladder dysfunction	Disease	D005705
15737522	309	324	pseudolithiasis	Disease	D001660
15737522	409	424	pseudolithiasis	Disease	D001660
15737522	467	478	ceftriaxone	Chemical	D002443
15737522	572	583	ceftriaxone	Chemical	D002443
15737522	721	736	pseudolithiasis	Disease	D001660
15737522	884	899	pseudolithiasis	Disease	D001660
15737522	963	978	pseudolithiasis	Disease	D001660
15737522	induced	D002443	D001660
16005948|a|The illicit use of cocaine continues in epidemic proportions and treatment for cocaine overdose remains elusive. Current protein-based technology offers a new therapeutic venue by which antibodies bind the drug in the blood stream, inactivating its toxic effects. The therapeutic potential of the anticocaine antibody GNC92H2 was examined using a model of cocaine overdose. Swiss albino mice prepared with intrajugular catheters were tested in photocell cages after administration of 93 mg/kg (LD50) of cocaine and GNC92H2 infusions ranging from 30 to 190 mg/kg. GNC92H2 was delivered 30 min before, concomitantly or 3 min after cocaine treatment. Significant blockade of cocaine toxicity was observed with the higher dose of GNC92H2 (190 mg/kg), where premorbid behaviors were reduced up to 40%, seizures up to 77% and death by 72%. Importantly, GNC92H2 prevented death even post-cocaine injection. The results support the important potential of GNC92H2 as a therapeutic tool against cocaine overdose.
16005948|t|Evaluation of the anticocaine monoclonal antibody GNC92H2 as an immunotherapy for cocaine overdose.
16005948	50	57	GNC92H2	Chemical	-1
16005948	82	98	cocaine overdose	Disease	D062787
16005948	119	126	cocaine	Chemical	D003042
16005948	179	195	cocaine overdose	Disease	D062787
16005948	418	425	GNC92H2	Chemical	-1
16005948	456	472	cocaine overdose	Disease	D062787
16005948	603	610	cocaine	Chemical	D003042
16005948	615	622	GNC92H2	Chemical	-1
16005948	663	670	GNC92H2	Chemical	-1
16005948	729	736	cocaine	Chemical	D003042
16005948	772	779	cocaine	Chemical	D003042
16005948	780	788	toxicity	Disease	D064420
16005948	826	833	GNC92H2	Chemical	-1
16005948	897	905	seizures	Disease	D012640
16005948	920	925	death	Disease	D003643
16005948	947	954	GNC92H2	Chemical	-1
16005948	965	970	death	Disease	D003643
16005948	981	988	cocaine	Chemical	D003042
16005948	1047	1054	GNC92H2	Chemical	-1
16005948	1085	1101	cocaine overdose	Disease	D062787
16005948	treated	-1	D062787
16005948	induced	D003042	D064420
16005948	treated	-1	D064420
16005948	treated	-1	D012640
16005948	treated	-1	D003643
16005948	induced	D003042	D012640
16005948	induced	D003042	D003643
16005948	induced	D003042	D062787
1601297|a|The electrocardiograms (ECG) of 99 cocaine-abusing patients were compared with the ECGs of 50 schizophrenic controls. Eleven of the cocaine abusers and none of the controls had ECG evidence of significant myocardial injury defined as myocardial infarction, ischemia, and bundle branch block.
1601297|t|Electrocardiographic evidence of myocardial injury in psychiatrically hospitalized cocaine abusers.
1601297	33	50	myocardial injury	Disease	D009202
1601297	83	90	cocaine	Chemical	D003042
1601297	135	142	cocaine	Chemical	D003042
1601297	194	207	schizophrenic	Disease	D012559
1601297	232	239	cocaine	Chemical	D003042
1601297	305	322	myocardial injury	Disease	D009202
1601297	334	355	myocardial infarction	Disease	D009203
1601297	357	365	ischemia	Disease	D007511
1601297	371	390	bundle branch block	Disease	D002037
1601297	induced	D003042	D009202
1601297	induced	D003042	D009203
1601297	induced	D003042	D007511
1601297	induced	D003042	D002037
16181582|a|Valproate-induced encephalopathy is a rare syndrome that may manifest in otherwise normal epileptic individuals. It may even present in patients who have tolerated this medicine well in the past. It is usually but not necessarily associated with hyperammonemia. The EEG shows characteristic triphasic waves in most patients with this complication. A case of valproate-induced encephalopathy is presented. The problems in diagnosing this condition are subsequently discussed.
16181582|t|Valproate-induced encephalopathy.
16181582	0	9	Valproate	Chemical	D014635
16181582	18	32	encephalopathy	Disease	D001927
16181582	34	43	Valproate	Chemical	D014635
16181582	52	66	encephalopathy	Disease	D001927
16181582	124	133	epileptic	Disease	D004827
16181582	280	294	hyperammonemia	Disease	D022124
16181582	392	401	valproate	Chemical	D014635
16181582	410	424	encephalopathy	Disease	D001927
16181582	induced	D014635	D001927
16181582	treated	D014635	D004827
16181582	induced	D014635	D022124
16274958|a|We report the case of a woman complaining of dysphonia while she was treated by acitretin. Her symptoms totally regressed after drug withdrawal and reappeared when acitretin was reintroduced. To our knowledge, this is the first case of acitretin-induced dysphonia. This effect may be related to the pharmacological effect of this drug on mucous membranes.
16274958|t|Recurrent dysphonia and acitretin.
16274958	10	19	dysphonia	Disease	D055154
16274958	24	33	acitretin	Chemical	D017255
16274958	80	89	dysphonia	Disease	D055154
16274958	115	124	acitretin	Chemical	D017255
16274958	199	208	acitretin	Chemical	D017255
16274958	271	280	acitretin	Chemical	D017255
16274958	289	298	dysphonia	Disease	D055154
16274958	induced	D017255	D055154
16330766|a|Abnormal processing of somatosensory inputs in the central nervous system (central sensitization) is the mechanism accounting for the enhanced pain sensitivity in the skin surrounding tissue injury (secondary hyperalgesia). Secondary hyperalgesia shares clinical characteristics with neurogenic hyperalgesia in patients with neuropathic pain. Abnormal brain responses to somatosensory stimuli have been found in patients with hyperalgesia as well as in normal subjects during experimental central sensitization. The aim of this study was to assess the effects of gabapentin, a drug effective in neuropathic pain patients, on brain processing of nociceptive information in normal and central sensitization states. Using functional magnetic resonance imaging (fMRI) in normal volunteers, we studied the gabapentin-induced modulation of brain activity in response to nociceptive mechanical stimulation of normal skin and capsaicin-induced secondary hyperalgesia. The dose of gabapentin was 1,800 mg per os, in a single administration. We found that (i) gabapentin reduced the activations in the bilateral operculoinsular cortex, independently of the presence of central sensitization; (ii) gabapentin reduced the activation in the brainstem, only during central sensitization; (iii) gabapentin suppressed stimulus-induced deactivations, only during central sensitization; this effect was more robust than the effect on brain activation. The observed drug-induced effects were not due to changes in the baseline fMRI signal. These findings indicate that gabapentin has a measurable antinociceptive effect and a stronger antihyperalgesic effect most evident in the brain areas undergoing deactivation, thus supporting the concept that gabapentin is more effective in modulating nociceptive transmission when central sensitization is present.
16330766|t|Pharmacological modulation of pain-related brain activity during normal and central sensitization states in humans.
16330766	30	34	pain	Disease	D010146
16330766	259	263	pain	Disease	D010146
16330766	300	313	tissue injury	Disease	D017695
16330766	315	337	secondary hyperalgesia	Disease	D006930
16330766	340	362	Secondary hyperalgesia	Disease	D006930
16330766	400	423	neurogenic hyperalgesia	Disease	D006930
16330766	441	457	neuropathic pain	Disease	D009437
16330766	542	554	hyperalgesia	Disease	D006930
16330766	679	689	gabapentin	Chemical	C040029
16330766	711	727	neuropathic pain	Disease	D009437
16330766	917	927	gabapentin	Chemical	C040029
16330766	1034	1043	capsaicin	Chemical	D002211
16330766	1052	1074	secondary hyperalgesia	Disease	D006930
16330766	1088	1098	gabapentin	Chemical	C040029
16330766	1166	1176	gabapentin	Chemical	C040029
16330766	1303	1313	gabapentin	Chemical	C040029
16330766	1396	1406	gabapentin	Chemical	C040029
16330766	1666	1676	gabapentin	Chemical	C040029
16330766	1846	1856	gabapentin	Chemical	C040029
16330766	treated	C040029	D006930
16330766	treated	C040029	D009437
16330766	induced	D002211	D010146
16330766	treated	C040029	D010146
16330766	induced	D002211	D006930
16330766	Association	D002211	D017695
16330766	Association	D002211	D009437
16330766	treated	C040029	D017695
16403073|a|Ketoconazole is not known to be proarrhythmic without concomitant use of QT interval-prolonging drugs. We report a woman with coronary artery disease who developed a markedly prolonged QT interval and torsades de pointes (TdP) after taking ketoconazole for treatment of fungal infection. Her QT interval returned to normal upon withdrawal of ketoconazole. Genetic study did not find any mutation in her genes that encode cardiac IKr channel proteins. We postulate that by virtue of its direct blocking action on IKr, ketoconazole alone may prolong QT interval and induce TdP. This calls for attention when ketoconazole is administered to patients with risk factors for acquired long QT syndrome.
16403073|t|Ketoconazole induced torsades de pointes without concomitant use of QT interval-prolonging drug.
16403073	0	12	Ketoconazole	Chemical	D007654
16403073	21	40	torsades de pointes	Disease	D016171
16403073	97	109	Ketoconazole	Chemical	D007654
16403073	223	246	coronary artery disease	Disease	D003324
16403073	272	293	prolonged QT interval	Disease	D008133
16403073	298	317	torsades de pointes	Disease	D016171
16403073	319	322	TdP	Disease	D016171
16403073	337	349	ketoconazole	Chemical	D007654
16403073	367	383	fungal infection	Disease	D009181
16403073	439	451	ketoconazole	Chemical	D007654
16403073	614	626	ketoconazole	Chemical	D007654
16403073	668	671	TdP	Disease	D016171
16403073	703	715	ketoconazole	Chemical	D007654
16403073	775	791	long QT syndrome	Disease	D008133
16403073	induced	D007654	D016171
16403073	induced	D007654	D008133
16403073	treated	D007654	D009181
16428221|a|Methylphenidate is structurally and functionally similar to amphetamine. Cerebral vasculitis associated with amphetamine abuse is well documented, and in rare cases ischaemic stroke has been reported after methylphenidate intake in children. We report the case of a 63-year-old female who was treated with methylphenidate due to hyperactivity and suffered from multiple ischaemic strokes. We consider drug-induced cerebral vasculitis as the most likely cause of recurrent ischaemic strokes in the absence of any pathological findings during the diagnostic work-up. We conclude that methylphenidate mediated vasculitis should be considered in patients with neurological symptoms and a history of methylphenidate therapy. This potential side-effect, though very rare, represents one more reason to be very restrictive in the use of methylphenidate.
16428221|t|Cerebral vasculitis following oral methylphenidate intake in an adult: a case report.
16428221	0	19	Cerebral vasculitis	Disease	D020293
16428221	35	50	methylphenidate	Chemical	D008774
16428221	86	101	Methylphenidate	Chemical	D008774
16428221	146	157	amphetamine	Chemical	D000661
16428221	159	178	Cerebral vasculitis	Disease	D020293
16428221	195	212	amphetamine abuse	Disease	D019969
16428221	251	267	ischaemic stroke	Disease	D002544
16428221	292	307	methylphenidate	Chemical	D008774
16428221	392	407	methylphenidate	Chemical	D008774
16428221	415	428	hyperactivity	Disease	D006948
16428221	456	473	ischaemic strokes	Disease	D002544
16428221	500	519	cerebral vasculitis	Disease	D020293
16428221	558	575	ischaemic strokes	Disease	D002544
16428221	668	683	methylphenidate	Chemical	D008774
16428221	693	703	vasculitis	Disease	D014657
16428221	781	796	methylphenidate	Chemical	D008774
16428221	916	931	methylphenidate	Chemical	D008774
16428221	induced	D008774	D020293
16428221	induced	D008774	D002544
16428221	induced	D000661	D020293
16428221	treated	D008774	D006948
16574712|a|In recent years working memory deficits have been reported in users of MDMA (3,4-methylenedioxymethamphetamine, ecstasy). The current study aimed to assess the impact of MDMA use on three separate central executive processes (set shifting, inhibition and memory updating) and also on "prefrontal" mediated social and emotional judgement processes. Fifteen polydrug ecstasy users and 15 polydrug non-ecstasy user controls completed a general drug use questionnaire, the Brixton Spatial Anticipation task (set shifting), Backward Digit Span procedure (memory updating), Inhibition of Return (inhibition), an emotional intelligence scale, the Tromso Social Intelligence Scale and the Dysexecutive Questionnaire (DEX). Compared with MDMA-free polydrug controls, MDMA polydrug users showed impairments in set shifting and memory updating, and also in social and emotional judgement processes. The latter two deficits remained significant after controlling for other drug use. These data lend further support to the proposal that cognitive processes mediated by the prefrontal cortex may be impaired by recreational ecstasy use.
16574712|t|MDMA polydrug users show process-specific central executive impairments coupled with impaired social and emotional judgement processes.
16574712	0	4	MDMA	Chemical	D018817
16574712	85	134	impaired social and emotional judgement processes	Disease	D003072
16574712	160	175	memory deficits	Disease	D008569
16574712	207	211	MDMA	Chemical	D018817
16574712	213	246	3,4-methylenedioxymethamphetamine	Chemical	D018817
16574712	248	255	ecstasy	Chemical	D018817
16574712	306	310	MDMA	Chemical	D018817
16574712	501	508	ecstasy	Chemical	D018817
16574712	535	542	ecstasy	Chemical	D018817
16574712	865	869	MDMA	Chemical	D018817
16574712	894	898	MDMA	Chemical	D018817
16574712	1246	1253	ecstasy	Chemical	D018817
16574712	induced	D018817	D003072
16574712	induced	D018817	D008569
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|t|Cardiovascular risk with cyclooxygenase inhibitors: general problem with substance specific differences?
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	induced	D016861	D009203
16586083	induced	D016861	D002318
16586083	induced	D016861	D020521
16586083	induced	D016861	D006973
16586083	induced	D016861	D006333
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|t|Pilocarpine seizures cause age-dependent impairment in auditory location discrimination.
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	induced	D010862	D012640
16596970	induced	D010862	D013226
16596970	induced	D010862	D001308
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|t|Ethambutol-associated optic neuropathy.
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	induced	D004977	D014786
16710500	induced	D004977	D009901
16755009|a|The present study was aimed at investigating the effects of Daucus carota seeds on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. The ethanolic extract of Daucus carota seeds (DCE) was administered orally in three doses (100, 200, 400 mg/kg) for seven successive days to different groups of young and aged mice. Elevated plus maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam-, scopolamine- and ageing-induced amnesia served as the interoceptive behavioral models. DCE (200, 400 mg/kg, p.o.) showed significant improvement in memory scores of young and aged mice. The extent of memory improvement evoked by DCE was 23% at the dose of 200 mg/kg and 35% at the dose of 400 mg/kg in young mice using elevated plus maze. Similarly, significant improvements in memory scores were observed using passive avoidance apparatus and aged mice. Furthermore, DCE reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Daucus carota extract (200, 400 mg/kg, p.o.) reduced significantly the brain acetylcholinesterase activity and cholesterol levels in young and aged mice. The extent of inhibition of brain cholinesterase activity evoked by DCE at the dose of 400 mg/kg was 22% in young and 19% in aged mice. There was a remarkable reduction in total cholesterol level as well, to the extent of 23% in young and 21% in aged animals with this dose of DCE. Therefore, DCE may prove to be a useful remedy for the management of cognitive dysfunctions on account of its multifarious beneficial effects such as, memory improving property, cholesterol lowering property and anticholinesterase activity.
16755009|t|Pharmacological evidence for the potential of Daucus carota in the management of cognitive dysfunctions.
16755009	81	103	cognitive dysfunctions	Disease	D003072
16755009	221	232	cholesterol	Chemical	D002784
16755009	297	327	extract of Daucus carota seeds	Chemical	D010936
16755009	329	332	DCE	Chemical	D010936
16755009	582	590	Diazepam	Chemical	D003975
16755009	593	604	scopolamine	Chemical	D012601
16755009	625	632	amnesia	Disease	D000647
16755009	680	683	DCE	Chemical	D010936
16755009	822	825	DCE	Chemical	D010936
16755009	1061	1064	DCE	Chemical	D010936
16755009	1078	1085	amnesia	Disease	D000647
16755009	1097	1108	scopolamine	Chemical	D012601
16755009	1131	1139	diazepam	Chemical	D003975
16755009	1157	1178	Daucus carota extract	Chemical	D010936
16755009	1268	1279	cholesterol	Chemical	D002784
16755009	1379	1382	DCE	Chemical	D010936
16755009	1489	1500	cholesterol	Chemical	D002784
16755009	1588	1591	DCE	Chemical	D010936
16755009	1604	1607	DCE	Chemical	D010936
16755009	1662	1684	cognitive dysfunctions	Disease	D003072
16755009	1771	1782	cholesterol	Chemical	D002784
16755009	induced	D012601	D000647
16755009	induced	D002784	D000647
16755009	treated	D010936	D000647
16755009	induced	D012601	D003072
16755009	induced	D003975	D003072
16755009	treated	D010936	D003072
16755009	treated	D002784	D003072
16755009	induced	D003975	D000647
16858720|a|PURPOSE: To evaluate the frequency, severity and preventability of warfarin-induced cerebral haemorrhages due to warfarin and warfarin-drug interactions in patients living in the county of Osterg  tland, Sweden. METHODS: All patients with a diagnosed cerebral haemorrhage at three hospitals during the period 2000-2002 were identified. Medical records were studied retrospectively to evaluate whether warfarin and warfarin-drug interactions could have caused the cerebral haemorrhage. The proportion of possibly avoidable cases due to drug interactions was estimated. RESULTS: Among 593 patients with cerebral haemorrhage, 59 (10%) were assessed as related to warfarin treatment. This imply an incidence of 1.7/100,000 treatment years. Of the 59 cases, 26 (44%) had a fatal outcome, compared to 136 (25%) among the non-warfarin patients (p < 0.01). A warfarin-drug interaction could have contributed to the haemorrhage in 24 (41%) of the warfarin patients and in 7 of these (12%) the bleeding complication was considered being possible to avoid. CONCLUSIONS: Warfarin-induced cerebral haemorrhages are a major clinical problem with a high fatality rate. Almost half of the cases was related to a warfarin-drug interaction. A significant proportion of warfarin-related cerebral haemorrhages might have been prevented if greater caution had been taken when prescribing drugs known to interact with warfarin.
16858720|t|Cerebral haemorrhage induced by warfarin - the influence of drug-drug interactions.
16858720	0	20	Cerebral haemorrhage	Disease	D002543
16858720	32	40	warfarin	Chemical	D014859
16858720	151	159	warfarin	Chemical	D014859
16858720	168	189	cerebral haemorrhages	Disease	D002543
16858720	197	205	warfarin	Chemical	D014859
16858720	210	218	warfarin	Chemical	D014859
16858720	335	355	cerebral haemorrhage	Disease	D002543
16858720	485	493	warfarin	Chemical	D014859
16858720	498	506	warfarin	Chemical	D014859
16858720	547	567	cerebral haemorrhage	Disease	D002543
16858720	685	705	cerebral haemorrhage	Disease	D002543
16858720	744	752	warfarin	Chemical	D014859
16858720	903	911	warfarin	Chemical	D014859
16858720	935	943	warfarin	Chemical	D014859
16858720	991	1002	haemorrhage	Disease	D006470
16858720	1022	1030	warfarin	Chemical	D014859
16858720	1068	1076	bleeding	Disease	D006470
16858720	1143	1151	Warfarin	Chemical	D014859
16858720	1160	1181	cerebral haemorrhages	Disease	D002543
16858720	1280	1288	warfarin	Chemical	D014859
16858720	1335	1343	warfarin	Chemical	D014859
16858720	1352	1373	cerebral haemorrhages	Disease	D002543
16858720	1480	1488	warfarin	Chemical	D014859
16858720	induced	D014859	D006470
16858720	induced	D014859	D002543
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|t|Sustained clinical improvement of a patient with decompensated hepatitis B virus-related cirrhosis after treatment with lamivudine monotherapy.
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
16960342	1174	1201	hepatitis B surface antigen	Chemical	D006514
16960342	1174	1195	hepatitis B e antigen	Chemical	D006513
16960342	1206	1227	hepatitis B e antigen	Chemical	D006513
16960342	1289	1299	lamivudine	Chemical	D019259
16960342	1329	1338	cirrhosis	Disease	D005355
16960342	treated	D019259	D006509
16960342	treated	D019259	D008103
16960342	treated	D019259	D005355
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|t|Placebo-level incidence of extrapyramidal symptoms (EPS) with quetiapine in controlled studies of patients with bipolar mania.
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	induced	D008094	D014202
17042884	induced	D008094	D001480
17042884	induced	D006220	D017109
17042884	induced	D006220	D001480
17042884	treated	C069541	D017109
17042884	induced	D006220	D014202
17042884	treated	C069541	D001480
17244258|a|In cyclophosphamide-induced cystitis in the rat, detrusor function is impaired and the expression and effects of muscarinic receptors altered. Whether or not the neuronal transmission may be affected by cystitis was presently investigated. Responses of urinary strip preparations from control and cyclophosphamide-pretreated rats to electrical field stimulation and to agonists were assessed in the absence and presence of muscarinic, adrenergic and purinergic receptor antagonists. Generally, atropine reduced contractions, but in contrast to controls, it also reduced responses to low electrical field stimulation intensity (1-5 Hz) in inflamed preparations. In both types, purinoceptor desensitization with alpha,beta-methylene adenosine-5'-triphosphate (alpha,beta-meATP) caused further reductions at low frequencies (<10 Hz). The muscarinic receptor antagonists atropine, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP) ('M(1)/M(3)/M(5)-selective'), methoctramine ('M(2)-selective') and pirenzepine ('M(1)-selective') antagonized the tonic component of the electrical field stimulation-evoked contractile response more potently than the phasic component. 4-DAMP inhibited the tonic contractions in controls more potently than methoctramine and pirenzepine. In inflamed preparations, the muscarinic receptor antagonism on the phasic component of the electrical field stimulation-evoked contraction was decreased and the pirenzepine and 4-DAMP antagonism on the tonic component was much less efficient than in controls. In contrast to controls, methoctramine increased -- instead of decreased -- the tonic responses at high frequencies. While contractions to carbachol and ATP were the same in inflamed and in control strips when related to a reference potassium response, isoprenaline-induced relaxations were smaller in inflamed strips. Thus, in cystitis substantial changes of the efferent functional responses occur. While postjunctional beta-adrenoceptor-mediated relaxations are reduced, effects by prejunctional inhibitory muscarinic receptors may be increased.
17244258|t|In vitro characterization of parasympathetic and sympathetic responses in cyclophosphamide-induced cystitis in the rat.
17244258	74	90	cyclophosphamide	Chemical	D003520
17244258	99	107	cystitis	Disease	D003556
17244258	123	139	cyclophosphamide	Chemical	D003520
17244258	148	156	cystitis	Disease	D003556
17244258	323	331	cystitis	Disease	D003556
17244258	417	433	cyclophosphamide	Chemical	D003520
17244258	614	622	atropine	Chemical	D001285
17244258	830	876	alpha,beta-methylene adenosine-5'-triphosphate	Chemical	C002630
17244258	878	894	alpha,beta-meATP	Chemical	C002630
17244258	987	995	atropine	Chemical	D001285
17244258	997	1033	4-diphenylacetoxy-N-methylpiperidine	Chemical	C042375
17244258	1035	1041	4-DAMP	Chemical	C042375
17244258	1073	1086	methoctramine	Chemical	C054938
17244258	1110	1121	pirenzepine	Chemical	D010890
17244258	1278	1284	4-DAMP	Chemical	C042375
17244258	1349	1362	methoctramine	Chemical	C054938
17244258	1367	1378	pirenzepine	Chemical	D010890
17244258	1542	1553	pirenzepine	Chemical	D010890
17244258	1558	1564	4-DAMP	Chemical	C042375
17244258	1666	1679	methoctramine	Chemical	C054938
17244258	1780	1789	carbachol	Chemical	D002217
17244258	1794	1797	ATP	Chemical	D000255
17244258	1874	1883	potassium	Chemical	D011188
17244258	1894	1906	isoprenaline	Chemical	D007545
17244258	1969	1977	cystitis	Disease	D003556
17244258	induced	D003520	D003556
17244258	treated	C042375	D003556
17244258	induced	C054938	D003556
17244258	treated	D010890	D003556
17244258	treated	D007545	D003556
17244258	treated	D001285	D003556
17244258	treated	C002630	D003556
17261653|a|BACKGROUND: Inhibition of cardiac sympathetic tone represents an important strategy for treatment of cardiovascular disease, including arrhythmia, coronary heart disease, and chronic heart failure. Activation of presynaptic alpha2-adrenoceptors is the most widely accepted mechanism of action of the antisympathetic drug clonidine; however, other target proteins have been postulated to contribute to the in vivo actions of clonidine. METHODS AND RESULTS: To test whether clonidine elicits pharmacological effects independent of alpha2-adrenoceptors, we have generated mice with a targeted deletion of all 3 alpha2-adrenoceptor subtypes (alpha2ABC-/-). Alpha2ABC-/- mice were completely unresponsive to the analgesic and hypnotic effects of clonidine; however, clonidine significantly lowered heart rate in alpha2ABC-/- mice by up to 150 bpm. Clonidine-induced bradycardia in conscious alpha2ABC-/- mice was 32.3% (10 microg/kg) and 26.6% (100 microg/kg) of the effect in wild-type mice. A similar bradycardic effect of clonidine was observed in isolated spontaneously beating right atria from alpha2ABC-knockout and wild-type mice. Clonidine inhibited the native pacemaker current (I(f)) in isolated sinoatrial node pacemaker cells and the I(f)-generating hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 and HCN4 channels in transfected HEK293 cells. As a consequence of blocking I(f), clonidine reduced the slope of the diastolic depolarization and the frequency of pacemaker potentials in sinoatrial node cells from wild-type and alpha2ABC-knockout mice. CONCLUSIONS: Direct inhibition of cardiac HCN pacemaker channels contributes to the bradycardic effects of clonidine gene-targeted mice in vivo, and thus, clonidine-like drugs represent novel structures for future HCN channel inhibitors.
17261653|t|Direct inhibition of cardiac hyperpolarization-activated cyclic nucleotide-gated pacemaker channels by clonidine.
17261653	57	74	cyclic nucleotide	Chemical	D009712
17261653	103	112	clonidine	Chemical	D003000
17261653	215	237	cardiovascular disease	Disease	D002318
17261653	249	259	arrhythmia	Disease	D001145
17261653	261	283	coronary heart disease	Disease	D003327
17261653	297	310	heart failure	Disease	D006333
17261653	435	444	clonidine	Chemical	D003000
17261653	538	547	clonidine	Chemical	D003000
17261653	586	595	clonidine	Chemical	D003000
17261653	855	864	clonidine	Chemical	D003000
17261653	875	884	clonidine	Chemical	D003000
17261653	957	966	Clonidine	Chemical	D003000
17261653	975	986	bradycardia	Disease	D001919
17261653	1134	1143	clonidine	Chemical	D003000
17261653	1247	1256	Clonidine	Chemical	D003000
17261653	1399	1416	cyclic nucleotide	Chemical	D009712
17261653	1513	1522	clonidine	Chemical	D003000
17261653	1791	1800	clonidine	Chemical	D003000
17261653	1839	1848	clonidine	Chemical	D003000
17261653	induced	D003000	D001919
17261653	treated	D003000	D002318
17261653	treated	D003000	D001145
17261653	treated	D003000	D003327
17261653	treated	D003000	D006333
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|t|Carbamazepine-induced cardiac dysfunction. Characterization of two distinct clinical syndromes.
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	induced	D002220	D001919
1728915	induced	D002220	D054537
1728915	induced	D002220	D006331
1728915	induced	D002220	D062787
17400887|a|Autism is a neurodevelopmental disorder presenting before 3 years of age with deficits in communication and social skills and repetitive behaviors. In addition to genetic influences, recent studies suggest that prenatal drug or chemical exposures are risk factors for autism. Terbutaline, a beta2-adrenoceptor agonist used to arrest preterm labor, has been associated with increased concordance for autism in dizygotic twins. We studied the effects of terbutaline on microglial activation in different brain regions and behavioral outcomes in developing rats. Newborn rats were given terbutaline (10 mg/kg) daily on postnatal days (PN) 2 to 5 or PN 11 to 14 and examined 24 h after the last dose and at PN 30. Immunohistochemical studies showed that administration of terbutaline on PN 2 to 5 produced a robust increase in microglial activation on PN 30 in the cerebral cortex, as well as in cerebellar and cerebrocortical white matter. None of these effects occurred in animals given terbutaline on PN 11 to 14. In behavioral tests, animals treated with terbutaline on PN 2 to 5 showed consistent patterns of hyper-reactivity to novelty and aversive stimuli when assessed in a novel open field, as well as in the acoustic startle response test. Our findings indicate that beta2-adrenoceptor overstimulation during an early critical period results in microglial activation associated with innate neuroinflammatory pathways and behavioral abnormalities, similar to those described in autism. This study provides a useful animal model for understanding the neuropathological processes underlying autism spectrum disorders.
17400887|t|Neuroinflammation and behavioral abnormalities after neonatal terbutaline treatment in rats: implications for autism.
17400887	0	17	Neuroinflammation	Disease	D020078
17400887	22	46	behavioral abnormalities	Disease	D001523
17400887	62	73	terbutaline	Chemical	D013726
17400887	110	116	autism	Disease	D001321
17400887	118	124	Autism	Disease	D001321
17400887	130	157	neurodevelopmental disorder	Disease	D002658
17400887	196	239	deficits in communication and social skills	Disease	D003147
17400887	244	264	repetitive behaviors	Disease	D001523
17400887	386	392	autism	Disease	D001321
17400887	394	405	Terbutaline	Chemical	D013726
17400887	451	464	preterm labor	Disease	D007752
17400887	517	523	autism	Disease	D001321
17400887	570	581	terbutaline	Chemical	D013726
17400887	702	713	terbutaline	Chemical	D013726
17400887	886	897	terbutaline	Chemical	D013726
17400887	1103	1114	terbutaline	Chemical	D013726
17400887	1173	1184	terbutaline	Chemical	D013726
17400887	1545	1569	behavioral abnormalities	Disease	D001523
17400887	1601	1607	autism	Disease	D001321
17400887	1712	1737	autism spectrum disorders	Disease	D002659
17400887	induced	D013726	D020078
17400887	induced	D013726	D001523
17400887	Association	D013726	D001321
17400887	Association	D013726	D007752
17400887	Association	D013726	D002659
17400887	Association	D013726	D002658
17600377|a|To develop a novel and effective drug that could enhance cognitive function and neuroprotection, we newly synthesized maltolyl p-coumarate by the esterification of maltol and p-coumaric acid. In the present study, we investigated whether maltolyl p-coumarate could improve cognitive decline in scopolamine-injected rats and in amyloid beta peptide(1-42)-infused rats. Maltolyl p-coumarate was found to attenuate cognitive deficits in both rat models using passive avoidance test and to reduce apoptotic cell death observed in the hippocampus of the amyloid beta peptide(1-42)-infused rats. We also examined the neuroprotective effects of maltolyl p-coumarate in vitro using SH-SY5Y cells. Cells were pretreated with maltolyl p-coumarate, before exposed to amyloid beta peptide(1-42), glutamate or H2O2. We found that maltolyl p-coumarate significantly decreased apoptotic cell death and reduced reactive oxygen species, cytochrome c release, and caspase 3 activation. Taking these in vitro and in vivo results together, our study suggests that maltolyl p-coumarate is a potentially effective candidate against Alzheimer's disease that is characterized by wide spread neuronal death and progressive decline of cognitive function.
17600377|t|A novel compound, maltolyl p-coumarate, attenuates cognitive deficits and shows neuroprotective effects in vitro and in vivo dementia models.
17600377	18	38	maltolyl p-coumarate	Chemical	C524754
17600377	51	69	cognitive deficits	Disease	D003072
17600377	125	133	dementia	Disease	D003704
17600377	260	280	maltolyl p-coumarate	Chemical	C524754
17600377	306	312	maltol	Chemical	C008316
17600377	317	332	p-coumaric acid	Chemical	C032171
17600377	380	400	maltolyl p-coumarate	Chemical	C524754
17600377	415	432	cognitive decline	Disease	D003072
17600377	436	447	scopolamine	Chemical	D012601
17600377	469	495	amyloid beta peptide(1-42)	Chemical	C544092
17600377	510	530	Maltolyl p-coumarate	Chemical	C524754
17600377	554	572	cognitive deficits	Disease	D003072
17600377	691	717	amyloid beta peptide(1-42)	Chemical	C544092
17600377	780	800	maltolyl p-coumarate	Chemical	C524754
17600377	858	878	maltolyl p-coumarate	Chemical	C524754
17600377	898	924	amyloid beta peptide(1-42)	Chemical	C544092
17600377	926	935	glutamate	Chemical	D018698
17600377	939	943	H2O2	Chemical	D006861
17600377	959	979	maltolyl p-coumarate	Chemical	C524754
17600377	1186	1206	maltolyl p-coumarate	Chemical	C524754
17600377	1252	1271	Alzheimer's disease	Disease	D000544
17600377	1309	1323	neuronal death	Disease	D009410
17600377	1340	1369	decline of cognitive function	Disease	D003072
17600377	treated	C524754	D003704
17600377	induced	D012601	D003072
17600377	induced	C544092	D009410
17600377	induced	D018698	D009410
17600377	induced	D006861	D009410
17600377	treated	C524754	D000544
17600377	treated	C524754	D009410
17600377	induced	D012601	D000544
17600377	induced	C544092	D000544
17600377	treated	C524754	D003072
17600377	induced	C544092	D003072
17639754|a|Warfarin is the most widely used oral anticoagulant and is indicated for many clinical conditions. Levofloxacin, a fluoroquinolone, is one of the most commonly prescribed antibiotics in clinical practice and is effective against Gram-positive, Gram-negative, and atypical bacteria. While small prospective studies have not revealed any significant drug-drug interaction between warfarin and levofloxacin, several case reports have indicated that levofloxacin may significantly potentiate the anticoagulation effect of warfarin. We report 3 cases of serious bleeding complications that appear to be the result of the interaction between warfarin and levofloxacin. Physicians should be aware of this potential interaction and use caution when prescribing levofloxacin to patients taking warfarin.
17639754|t|Interaction between warfarin and levofloxacin: case series.
17639754	20	28	warfarin	Chemical	D014859
17639754	33	45	levofloxacin	Chemical	D064704
17639754	60	68	Warfarin	Chemical	D014859
17639754	159	171	Levofloxacin	Chemical	D064704
17639754	175	190	fluoroquinolone	Chemical	D024841
17639754	438	446	warfarin	Chemical	D014859
17639754	451	463	levofloxacin	Chemical	D064704
17639754	506	518	levofloxacin	Chemical	D064704
17639754	578	586	warfarin	Chemical	D014859
17639754	617	625	bleeding	Disease	D006470
17639754	696	704	warfarin	Chemical	D014859
17639754	709	721	levofloxacin	Chemical	D064704
17639754	813	825	levofloxacin	Chemical	D064704
17639754	845	853	warfarin	Chemical	D014859
17639754	induced	D014859	D006470
17639754	induced	D064704	D006470
17639754	induced	D024841	D006470
1786266|a|The rabbit syndrome is an extrapyramidal side effect associated with chronic neuroleptic therapy. Its occurrence in a patient being treated with imipramine is described, representing the first reported case of this syndrome in conjunction with antidepressants. Repeated cerebral perfusion SPECT scans revealed decreased basal ganglia perfusion while the movement disorder was present, and a return to normal perfusion when the rabbit syndrome resolved.
1786266|t|Rabbit syndrome, antidepressant use, and cerebral perfusion SPECT scan findings.
1786266	0	15	Rabbit syndrome	Disease	D001480
1786266	17	31	antidepressant	Chemical	D000928
1786266	85	100	rabbit syndrome	Disease	D001480
1786266	226	236	imipramine	Chemical	D007099
1786266	325	340	antidepressants	Chemical	D000928
1786266	391	424	decreased basal ganglia perfusion	Disease	D001480
1786266	435	452	movement disorder	Disease	D009069
1786266	508	523	rabbit syndrome	Disease	D001480
1786266	Association	D000928	D001480
1786266	induced	D007099	D001480
1786266	induced	D007099	D009069
1786266	Association	D000928	D009069
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|t|Myocardial Fas ligand expression increases susceptibility to AZT-induced cardiomyopathy.
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
17943461	1909	1925	cardiac dilation	Disease	D002311
17943461	1909	1928	cardiac dysfunction	Disease	D006331
17943461	induced	D015215	D002311
17943461	induced	D015215	D009202
17943461	induced	D015215	C538496
18023325|a|Acute peripheral neuropathy caused by a disulfiram overdose is very rare and there is no report of it leading to vocal fold palsy. A 49-year-old woman was transferred to our department because of quadriparesis, lancinating pain, sensory loss, and paresthesia of the distal limbs. One month previously, she had taken a single high dose of disulfiram (130 tablets of ALCOHOL STOP TAB, Shin-Poong Pharm. Co., Ansan, Korea) in a suicide attempt. She was not an alcoholic. For the first few days after ingestion, she was in a confused state and had mild to moderate ataxia and giddiness. She noticed hoarseness and distally accentuated motor and sensory dysfunction after she had recovered from this state. A nerve conduction study was consistent with severe sensorimotor axonal polyneuropathy. Laryngeal electromyography (thyroarytenoid muscle) showed ample denervation potentials. Laryngoscopy revealed asymmetric vocal fold movements during phonation. Her vocal change and weakness began to improve spontaneously about 3 weeks after transfer. This was a case of acute palsy of the recurrent laryngeal nerve and superimposed severe acute sensorimotor axonal polyneuropathy caused by high-dose disulfiram intoxication.
18023325|t|Acute vocal fold palsy after acute disulfiram intoxication.
18023325	6	22	vocal fold palsy	Disease	D014826
18023325	35	45	disulfiram	Chemical	D004221
18023325	66	87	peripheral neuropathy	Disease	D010523
18023325	100	110	disulfiram	Chemical	D004221
18023325	111	119	overdose	Disease	D062787
18023325	173	189	vocal fold palsy	Disease	D014826
18023325	256	269	quadriparesis	Disease	D011782
18023325	283	287	pain	Disease	D010146
18023325	289	301	sensory loss	Disease	C580162
18023325	307	318	paresthesia	Disease	D010292
18023325	398	408	disulfiram	Chemical	D004221
18023325	425	432	ALCOHOL	Chemical	D000431
18023325	621	627	ataxia	Disease	D001259
18023325	632	641	giddiness	Disease	D004244
18023325	655	665	hoarseness	Disease	D006685
18023325	834	848	polyneuropathy	Disease	D011115
18023325	1126	1131	palsy	Disease	D010243
18023325	1215	1229	polyneuropathy	Disease	D011115
18023325	1250	1260	disulfiram	Chemical	D004221
18023325	induced	D004221	D014826
18023325	induced	D004221	D001259
18023325	induced	D004221	D004244
18023325	induced	D004221	D006685
18023325	induced	D004221	D010243
18023325	induced	D004221	D011115
18023325	induced	D004221	D010523
18023325	Association	D004221	D062787
18023325	induced	D004221	D011782
18023325	induced	D004221	D010146
18023325	induced	D004221	C580162
18023325	induced	D004221	D010292
18083142|a|BACKGROUND: Cocaine is a widely abused psychostimulant that has both rewarding and aversive properties. While the mechanisms underlying cocaine's rewarding effects have been studied extensively, less attention has been paid to the unpleasant behavioral states induced by cocaine, such as anxiety. METHODS: In this study, we evaluated the performance of dopamine beta-hydroxylase knockout (Dbh -/-) mice, which lack norepinephrine (NE), in the elevated plus maze (EPM) to examine the contribution of noradrenergic signaling to cocaine-induced anxiety. RESULTS: We found that cocaine dose-dependently increased anxiety-like behavior in control (Dbh +/-) mice, as measured by a decrease in open arm exploration. The Dbh -/- mice had normal baseline performance in the EPM but were completely resistant to the anxiogenic effects of cocaine. Cocaine-induced anxiety was also attenuated in Dbh +/- mice following administration of disulfiram, a dopamine beta-hydroxylase (DBH) inhibitor. In experiments using specific adrenergic antagonists, we found that pretreatment with the beta-adrenergic receptor antagonist propranolol blocked cocaine-induced anxiety-like behavior in Dbh +/- and wild-type C57BL6/J mice, while the alpha(1) antagonist prazosin and the alpha(2) antagonist yohimbine had no effect. CONCLUSIONS: These results indicate that noradrenergic signaling via beta-adrenergic receptors is required for cocaine-induced anxiety in mice.
18083142|t|Norepinephrine signaling through beta-adrenergic receptors is critical for expression of cocaine-induced anxiety.
18083142	0	14	Norepinephrine	Chemical	D009638
18083142	89	96	cocaine	Chemical	D003042
18083142	105	112	anxiety	Disease	D001008
18083142	126	133	Cocaine	Chemical	D003042
18083142	250	257	cocaine	Chemical	D003042
18083142	385	392	cocaine	Chemical	D003042
18083142	402	409	anxiety	Disease	D001008
18083142	467	475	dopamine	Chemical	D004298
18083142	529	543	norepinephrine	Chemical	D009638
18083142	545	547	NE	Chemical	D009638
18083142	640	647	cocaine	Chemical	D003042
18083142	656	663	anxiety	Disease	D001008
18083142	688	695	cocaine	Chemical	D003042
18083142	723	730	anxiety	Disease	D001008
18083142	942	949	cocaine	Chemical	D003042
18083142	951	958	Cocaine	Chemical	D003042
18083142	967	974	anxiety	Disease	D001008
18083142	1039	1049	disulfiram	Chemical	D004221
18083142	1053	1061	dopamine	Chemical	D004298
18083142	1222	1233	propranolol	Chemical	D011433
18083142	1242	1249	cocaine	Chemical	D003042
18083142	1258	1265	anxiety	Disease	D001008
18083142	1350	1358	prazosin	Chemical	D011224
18083142	1387	1396	yohimbine	Chemical	D015016
18083142	1523	1530	cocaine	Chemical	D003042
18083142	1539	1546	anxiety	Disease	D001008
18083142	treated	D009638	D001008
18083142	treated	D004221	D001008
18083142	treated	D011433	D001008
18083142	induced	D003042	D001008
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|t|Dexmedetomidine and cardiac protection for non-cardiac surgery: a meta-analysis of randomised controlled trials.
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	treated	D020927	D009203
18086064	treated	D020927	D017202
18086064	induced	D020927	D007022
18086064	induced	D020927	D001919
18182964|a|OBJECTIVE: To examine the safety and tolerability of clonidine used alone or with methylphenidate in children with attention-deficit/hyperactivity disorder (ADHD). METHOD: In a 16-week multicenter, double-blind trial, 122 children with ADHD were randomly assigned to clonidine (n = 31), methylphenidate (n = 29), clonidine and methylphenidate (n = 32), or placebo (n = 30). Doses were flexibly titrated up to 0.6 mg/day for clonidine and 60 mg/day for methylphenidate (both with divided dosing). Groups were compared regarding adverse events and changes from baseline to week 16 in electrocardiograms and vital signs. RESULTS: There were more incidents of bradycardia in subjects treated with clonidine compared with those not treated with clonidine (17.5% versus 3.4%; p =.02), but no other significant group differences regarding electrocardiogram and other cardiovascular outcomes. There were no suggestions of interactions between clonidine and methylphenidate regarding cardiovascular outcomes. Moderate or severe adverse events were more common in subjects on clonidine (79.4% versus 49.2%; p =.0006) but not associated with higher rates of early study withdrawal. Drowsiness was common on clonidine, but generally resolved by 6 to 8 weeks. CONCLUSIONS: Clonidine, used alone or with methylphenidate, appears safe and well tolerated in childhood ADHD. Physicians prescribing clonidine should monitor for bradycardia and advise patients about the high likelihood of initial drowsiness.
18182964|t|Clonidine for attention-deficit/hyperactivity disorder: II. ECG changes and adverse events analysis.
18182964	0	9	Clonidine	Chemical	D003000
18182964	14	54	attention-deficit/hyperactivity disorder	Disease	D001289
18182964	154	163	clonidine	Chemical	D003000
18182964	183	198	methylphenidate	Chemical	D008774
18182964	216	256	attention-deficit/hyperactivity disorder	Disease	D001289
18182964	258	262	ADHD	Disease	D001289
18182964	337	341	ADHD	Disease	D001289
18182964	368	377	clonidine	Chemical	D003000
18182964	388	403	methylphenidate	Chemical	D008774
18182964	414	423	clonidine	Chemical	D003000
18182964	428	443	methylphenidate	Chemical	D008774
18182964	525	534	clonidine	Chemical	D003000
18182964	553	568	methylphenidate	Chemical	D008774
18182964	757	768	bradycardia	Disease	D001919
18182964	794	803	clonidine	Chemical	D003000
18182964	841	850	clonidine	Chemical	D003000
18182964	1036	1045	clonidine	Chemical	D003000
18182964	1050	1065	methylphenidate	Chemical	D008774
18182964	1167	1176	clonidine	Chemical	D003000
18182964	1272	1282	Drowsiness	Disease	D006970
18182964	1297	1306	clonidine	Chemical	D003000
18182964	1361	1370	Clonidine	Chemical	D003000
18182964	1391	1406	methylphenidate	Chemical	D008774
18182964	1453	1457	ADHD	Disease	D001289
18182964	1482	1491	clonidine	Chemical	D003000
18182964	1511	1522	bradycardia	Disease	D001919
18182964	1580	1590	drowsiness	Disease	D006970
18182964	induced	D003000	D001919
18182964	induced	D003000	D006970
18182964	treated	D003000	D001289
18182964	treated	D008774	D001289
18208574|a|OBJECTIVES: To correlate optical density and percent inhibition of a two-step heparin-induced thrombocytopenia (HIT) antigen assay with thrombosis; the assay utilizes reaction inhibition characteristics of a high heparin concentration. PATIENTS AND METHODS: Patients with more than 50% decrease in platelet count or thrombocytopenia (<150 x 10(9)/L) after exposure to heparin, who had a positive two-step antigen assay [optical density (OD) >0.4 and >50 inhibition with high concentration of heparin] were included in the study. RESULTS: Forty of 94 HIT patients had thrombosis at diagnosis; 54/94 had isolated-HIT without thrombosis. Eight of the isolated-HIT patients developed thrombosis within the next 30 d; thus, a total of 48 patients had thrombosis at day 30. At diagnosis there was no significant difference in OD between HIT patients with thrombosis and those with isolated-HIT. However, OD was significantly higher in all patients with thrombosis (n = 48, 1.34 +/- 0.89), including isolated-HIT patients who later developed thrombosis within 30 d (n = 8, 1.84 +/- 0.64) as compared to isolated-HIT patients who did not develop thrombosis (0.96 +/- 0.75; P = 0.011 and P = 0.008). The Receiver Operative Characteristic Curve showed that OD >1.27 in the isolated-HIT group had a significantly higher chance of developing thrombosis by day 30. None of these groups showed significant difference in percent inhibition. Multivariate analysis showed a 2.8-fold increased risk of thrombosis in females. Similarly, thrombotic risk increased with age and OD values. CONCLUSION: Higher OD is associated with significant risk of subsequent thrombosis in patients with isolated-HIT; percent inhibition, however, was not predictive.
18208574|t|Higher optical density of an antigen assay predicts thrombosis in patients with heparin-induced thrombocytopenia.
18208574	52	62	thrombosis	Disease	D013927
18208574	80	87	heparin	Chemical	D006493
18208574	96	112	thrombocytopenia	Disease	D013921
18208574	192	199	heparin	Chemical	D006493
18208574	208	224	thrombocytopenia	Disease	D013921
18208574	226	229	HIT	Disease	D013921
18208574	250	260	thrombosis	Disease	D013927
18208574	327	334	heparin	Chemical	D006493
18208574	430	446	thrombocytopenia	Disease	D013921
18208574	482	489	heparin	Chemical	D006493
18208574	606	613	heparin	Chemical	D006493
18208574	664	667	HIT	Disease	D013921
18208574	681	691	thrombosis	Disease	D013927
18208574	725	728	HIT	Disease	D013921
18208574	737	747	thrombosis	Disease	D013927
18208574	771	774	HIT	Disease	D013921
18208574	794	804	thrombosis	Disease	D013927
18208574	860	870	thrombosis	Disease	D013927
18208574	945	948	HIT	Disease	D013921
18208574	963	973	thrombosis	Disease	D013927
18208574	998	1001	HIT	Disease	D013921
18208574	1061	1071	thrombosis	Disease	D013927
18208574	1116	1119	HIT	Disease	D013921
18208574	1149	1159	thrombosis	Disease	D013927
18208574	1219	1222	HIT	Disease	D013921
18208574	1252	1262	thrombosis	Disease	D013927
18208574	1386	1389	HIT	Disease	D013921
18208574	1444	1454	thrombosis	Disease	D013927
18208574	1598	1608	thrombosis	Disease	D013927
18208574	1632	1642	thrombotic	Disease	D013927
18208574	1754	1764	thrombosis	Disease	D013927
18208574	1791	1794	HIT	Disease	D013921
18208574	induced	D006493	D013921
18208574	induced	D006493	D013927
18329269|a|A series of N-pyrimidinyl-2-phenoxyacetamide adenosine A(2A) antagonists is described. SAR studies led to compound 14 with excellent potency (K(i) = 0.4 nM), selectivity (A(1)/A(2A) > 100), and efficacy (MED 10 mg/kg p.o.) in the rat haloperidol-induced catalepsy model for Parkinson's disease.
18329269|t|Synthesis of N-pyrimidinyl-2-phenoxyacetamides as adenosine A2A receptor antagonists.
18329269	13	46	N-pyrimidinyl-2-phenoxyacetamides	Chemical	D010642
18329269	50	59	adenosine	Chemical	D000241
18329269	98	130	N-pyrimidinyl-2-phenoxyacetamide	Chemical	D010642
18329269	131	140	adenosine	Chemical	D000241
18329269	320	331	haloperidol	Chemical	D006220
18329269	340	349	catalepsy	Disease	D002375
18329269	360	379	Parkinson's disease	Disease	D010300
18329269	treated	D010642	D002375
18329269	treated	D010642	D010300
18329269	induced	D006220	D002375
1833784|a|Previous studies have suggested that repeated exposure of rats to the drug or to the experimental environment is necessary to observe nicotine-induced locomotor stimulation. In the present study the role of habituation to the experimental environment on the stimulant effect of nicotine in rats was examined. In addition, the role of dopamine receptors in mediating nicotine-induced locomotor stimulation was investigated by examining the effects of selective D1 and D2 dopamine receptor antagonists on activity induced by nicotine. Locomotor activity was assessed in male Sprague-Dawley rats tested in photocell cages. Nicotine (1.0 mg/kg) caused a significant increase in locomotor activity in rats that were habituated to the test environment, but had only a weak and delayed stimulant action in rats that were unfamiliar with the test environment. The stimulant action of nicotine was blocked by the central nicotinic antagonist mecamylamine but not by the peripheral nicotinic blocker hexamethonium, indicating that the response is probably mediated by central nicotinic receptors. Nicotine-induced hyperactivity was blocked by the selective D1 antagonist SCH 23390, the selective D2 antagonist raclopride and the D1/D2 antagonist fluphenazine. Pretreatment with the D2 agonist PHNO enhanced nicotine-induced hyperactivity, whereas the D1 agonist SKF 38393 had no effect. The results indicate that acute nicotine injection induces a pronounced hyperactivity in rats habituated to the test environment. The effect appears to be mediated by central nicotine receptors, possibly located on dopaminergic neurons, and also requires the activation of both D1 and D2 dopamine receptors.
1833784|t|Evidence for an involvement of D1 and D2 dopamine receptors in mediating nicotine-induced hyperactivity in rats.
1833784	41	49	dopamine	Chemical	D004298
1833784	73	81	nicotine	Chemical	D009538
1833784	90	103	hyperactivity	Disease	D006948
1833784	247	255	nicotine	Chemical	D009538
1833784	391	399	nicotine	Chemical	D009538
1833784	447	455	dopamine	Chemical	D004298
1833784	479	487	nicotine	Chemical	D009538
1833784	583	591	dopamine	Chemical	D004298
1833784	636	644	nicotine	Chemical	D009538
1833784	733	741	Nicotine	Chemical	D009538
1833784	775	805	increase in locomotor activity	Disease	D006948
1833784	989	997	nicotine	Chemical	D009538
1833784	1046	1058	mecamylamine	Chemical	D008464
1833784	1103	1116	hexamethonium	Chemical	D018738
1833784	1200	1208	Nicotine	Chemical	D009538
1833784	1217	1230	hyperactivity	Disease	D006948
1833784	1274	1283	SCH 23390	Chemical	C534628
1833784	1313	1323	raclopride	Chemical	D020891
1833784	1349	1361	fluphenazine	Chemical	D005476
1833784	1396	1400	PHNO	Chemical	-1
1833784	1410	1418	nicotine	Chemical	D009538
1833784	1427	1440	hyperactivity	Disease	D006948
1833784	1465	1474	SKF 38393	Chemical	D015647
1833784	1522	1530	nicotine	Chemical	D009538
1833784	1562	1575	hyperactivity	Disease	D006948
1833784	1665	1673	nicotine	Chemical	D009538
1833784	1778	1786	dopamine	Chemical	D004298
1833784	treated	D004298	D006948
1833784	treated	D008464	D006948
1833784	induced	D009538	D006948
1833784	treated	C534628	D006948
1833784	treated	D020891	D006948
1833784	treated	D005476	D006948
1833784	induced	-1	D006948
1835291|a|The bronchodilator effects of a single dose of ipratropium bromide aerosol (36 micrograms) and short-acting theophylline tablets (dose titrated to produce serum levels of 10-20 micrograms/mL) were compared in a double-blind, placebo-controlled crossover study in 21 patients with stable, chronic obstructive pulmonary disease. Mean peak forced expiratory volume in 1 second (FEV1) increases over baseline and the proportion of patients attaining at least a 15% increase in the FEV1 (responders) were 31% and 90%, respectively, for ipratropium and 17% and 50%, respectively, for theophylline. The average FEV1 increases during the 6-hour observation period were 18% for ipratropium and 8% for theophylline. The mean duration of action was 3.8 hours with ipratropium and 2.4 hours with theophylline. While side effects were rare, those experienced after theophylline use did involve the cardiovascular and gastrointestinal systems. These results show that ipratropium is a more potent bronchodilator than oral theophylline in patients with chronic airflow obstruction.
1835291|t|Acute bronchodilating effects of ipratropium bromide and theophylline in chronic obstructive pulmonary disease.
1835291	33	52	ipratropium bromide	Chemical	D009241
1835291	57	69	theophylline	Chemical	D013806
1835291	73	110	chronic obstructive pulmonary disease	Disease	D029424
1835291	159	178	ipratropium bromide	Chemical	D009241
1835291	220	232	theophylline	Chemical	D013806
1835291	400	437	chronic obstructive pulmonary disease	Disease	D029424
1835291	643	654	ipratropium	Chemical	D009241
1835291	690	702	theophylline	Chemical	D013806
1835291	781	792	ipratropium	Chemical	D009241
1835291	804	816	theophylline	Chemical	D013806
1835291	865	876	ipratropium	Chemical	D009241
1835291	896	908	theophylline	Chemical	D013806
1835291	964	976	theophylline	Chemical	D013806
1835291	997	1040	cardiovascular and gastrointestinal systems	Disease	-1
1835291	997	1019	cardiovascular systems	Disease	D002318
1835291	1016	1040	gastrointestinal systems	Disease	D005767
1835291	1033	1055	cardiovascular systems	Disease	D002318
1835291	1066	1077	ipratropium	Chemical	D009241
1835291	1120	1132	theophylline	Chemical	D013806
1835291	1150	1177	chronic airflow obstruction	Disease	D029424
1835291	treated	D009241	D029424
1835291	treated	D013806	D029424
18417364|a|The pathomechanism of nicotine-induced nystagmus (NIN) is unknown. The aim of this study was to delineate brain structures that are involved in NIN generation. Eight healthy volunteers inhaled nicotine in darkness during a functional magnetic resonance imaging (fMRI) experiment; eye movements were registered using video-oculography. NIN correlated with blood oxygen level-dependent (BOLD) activity levels in a midpontine site in the posterior basis pontis. NIN-induced midpontine activation may correspond to activation of the dorsomedial pontine nuclei and the nucleus reticularis tegmenti pontis, structures known to participate in the generation of multidirectional saccades and smooth pursuit eye movements.
18417364|t|Nicotine-induced nystagmus correlates with midpontine activation.
18417364	0	8	Nicotine	Chemical	D009538
18417364	17	26	nystagmus	Disease	D009759
18417364	88	96	nicotine	Chemical	D009538
18417364	105	114	nystagmus	Disease	D009759
18417364	116	119	NIN	Disease	D009759
18417364	210	213	NIN	Disease	D009759
18417364	259	267	nicotine	Chemical	D009538
18417364	401	404	NIN	Disease	D009759
18417364	427	433	oxygen	Chemical	D010100
18417364	525	528	NIN	Disease	D009759
18417364	induced	D009538	D009759
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|t|Complete atrioventricular block secondary to lithium therapy.
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	induced	D008094	D012804
18441470	induced	D008094	D054537
18441470	induced	D008094	D013575
18442015|a|Studies concerning with pathogenesis of gastric hemorrhage and mucosal ulceration produced in atherosclerotic rats are lacking. The aim of this study is to examine the role of gastric acid back-diffusion, mast cell histamine release, lipid peroxide (LPO) generation and mucosal microvascular permeability in modulating gastric hemorrhage and ulcer in rats with atherosclerosis induced by coadministration of vitamin D2 and cholesterol. Additionally, the protective effect of verapamil on this ulcer model was evaluated. Male Wistar rats were challenged intragastrically once daily for 9 days with 1.0 ml/kg of corn oil containing vitamin D2 and cholesterol to induce atherosclerosis. Control rats received corn oil only. After gastric surgery, rat stomachs were irrigated for 3 h with either simulated gastric juice or normal saline. Gastric acid back-diffusion, mucosal LPO generation, histamine concentration, microvascular permeability, luminal hemoglobin content and ulcer areas were determined. Elevated atherosclerotic parameters, such as serum calcium, total cholesterol and low-density lipoprotein concentration were obtained in atherosclerotic rats. Severe gastric ulcers accompanied with increased ulcerogenic factors, including gastric acid back-diffusion, histamine release, LPO generation and luminal hemoglobin content were also observed in these rats. Moreover, a positive correlation of histamine to gastric hemorrhage and to ulcer was found in those atherosclerotic rats. This hemorrhagic ulcer and various ulcerogenic parameters were dose-dependently ameliorated by daily intragastric verapamil. Atherosclerosis could produce gastric hemorrhagic ulcer via aggravation of gastric acid back-diffusion, LPO generation, histamine release and microvascular permeability that could be ameliorated by verapamil in rats.
18442015|t|Protective effect of verapamil on gastric hemorrhagic ulcers in severe atherosclerotic rats.
18442015	21	30	verapamil	Chemical	D014700
18442015	34	53	gastric hemorrhagic	Disease	D006471
18442015	54	60	ulcers	Disease	D014456
18442015	71	86	atherosclerotic	Disease	D050197
18442015	133	151	gastric hemorrhage	Disease	D006471
18442015	187	202	atherosclerotic	Disease	D050197
18442015	308	317	histamine	Chemical	D006632
18442015	412	430	gastric hemorrhage	Disease	D006471
18442015	435	440	ulcer	Disease	D014456
18442015	454	469	atherosclerosis	Disease	D050197
18442015	501	511	vitamin D2	Chemical	D004872
18442015	516	527	cholesterol	Chemical	D002784
18442015	568	577	verapamil	Chemical	D014700
18442015	586	591	ulcer	Disease	D014456
18442015	723	733	vitamin D2	Chemical	D004872
18442015	738	749	cholesterol	Chemical	D002784
18442015	760	775	atherosclerosis	Disease	D050197
18442015	980	989	histamine	Chemical	D006632
18442015	1033	1040	luminal	Chemical	D010634
18442015	1064	1069	ulcer	Disease	D014456
18442015	1102	1117	atherosclerotic	Disease	D050197
18442015	1144	1151	calcium	Chemical	D002118
18442015	1159	1170	cholesterol	Chemical	D002784
18442015	1230	1245	atherosclerotic	Disease	D050197
18442015	1267	1273	ulcers	Disease	D014456
18442015	1361	1370	histamine	Chemical	D006632
18442015	1399	1406	luminal	Chemical	D010634
18442015	1496	1505	histamine	Chemical	D006632
18442015	1509	1527	gastric hemorrhage	Disease	D006471
18442015	1535	1540	ulcer	Disease	D014456
18442015	1560	1575	atherosclerotic	Disease	D050197
18442015	1587	1598	hemorrhagic	Disease	D006471
18442015	1599	1604	ulcer	Disease	D014456
18442015	1696	1705	verapamil	Chemical	D014700
18442015	1707	1722	Atherosclerosis	Disease	D050197
18442015	1737	1756	gastric hemorrhagic	Disease	D006471
18442015	1757	1762	ulcer	Disease	D014456
18442015	1827	1836	histamine	Chemical	D006632
18442015	1905	1914	verapamil	Chemical	D014700
18442015	treated	D014700	D006471
18442015	induced	D004872	D050197
18442015	induced	D002784	D050197
18442015	treated	D014700	D014456
18442015	induced	D006632	D006471
18442015	induced	D006632	D014456
18503483|a|TAC has been shown to be a potent immunosuppressive agent for solid organ transplantation in pediatrics. Neurotoxicity is a potentially serious toxic effect. It is characterized by encephalopathy, headaches, seizures, or neurological deficits. Here, we describe an eight-and-a-half-yr-old male renal transplant recipient with right BN. MRI demonstrated hyperintense T2 signals in the cervical cord and right brachial plexus roots indicative of both myelitis and right brachial plexitis. Symptoms persisted for three months despite TAC dose reduction, administration of IVIG and four doses of methylprednisolone pulse therapy. Improvement and eventually full recovery only occurred after TAC was completely discontinued and successfully replaced by everolimus.
18503483|t|Recovery of tacrolimus-associated brachial neuritis after conversion to everolimus in a pediatric renal transplant recipient--case report and review of the literature.
18503483	12	22	tacrolimus	Chemical	D016559
18503483	34	51	brachial neuritis	Disease	D020968
18503483	72	82	everolimus	Chemical	C107135
18503483	168	171	TAC	Chemical	D016559
18503483	273	286	Neurotoxicity	Disease	D020258
18503483	349	363	encephalopathy	Disease	D001927
18503483	365	374	headaches	Disease	D006261
18503483	376	384	seizures	Disease	D012640
18503483	389	410	neurological deficits	Disease	D009461
18503483	617	625	myelitis	Disease	D009187
18503483	636	653	brachial plexitis	Disease	D020968
18503483	699	702	TAC	Chemical	D016559
18503483	760	778	methylprednisolone	Chemical	D008775
18503483	855	858	TAC	Chemical	D016559
18503483	916	926	everolimus	Chemical	C107135
18503483	induced	D016559	D020968
18503483	treated	C107135	D020968
18503483	treated	C107135	D020258
18503483	induced	D016559	D020258
18503483	induced	D016559	D001927
18503483	induced	D016559	D006261
18503483	induced	D016559	D012640
18503483	induced	D016559	D009461
18503483	induced	D016559	D009187
18560792|a|Valvular heart abnormalities have been reported in patients with Parkinson's disease (PD) treated with pergolide. However, the incidence and severity of these abnormalities vary from study to study and their course after drug withdrawal has not been systematically assessed. OBJECTIVES: To estimate the frequency and severity of valvular heart abnormality and its possible reversibility after drug withdrawal in a case-control study. METHODS: All PD patients in the Amiens area treated with pergolide were invited to attend a cardiologic assessment including transthoracic echocardiography. Thirty PD patients participated in the study. A second echocardiography was performed (median interval: 13 months) after pergolide withdrawal (n=10 patients). Controls were age- and sex-matched non-PD patients referred to the cardiology department. RESULTS: Compared to controls, aortic regurgitation (OR: 3.1; 95% IC: 1.1-8.8) and mitral regurgitation (OR: 10.7; 95% IC: 2.1-53) were more frequent in PD patients (tricuspid: NS). The number of affected valves (n=2.4+/-0.7) and the sum of regurgitation grades (n=2.8+/-1.09) were higher (p=0.008 and p=0.006, respectively) in the pergolide group. Severity of regurgitation was not correlated with pergolide cumulative dose. A restrictive pattern of valvular regurgitation, suggestive of the role of pergolide, was observed in 12/30 (40%) patients including two with heart failure. Pergolide was discontinued in 10 patients with valvular heart disease, resulting in a lower regurgitation grade (p=0.01) at the second transthoracic echocardiography and the two patients with heart failure returned to nearly normal clinical examination. This study supports the high frequency of restrictive valve regurgitation in PD patients treated with pergolide and reveals that a significant improvement is usual when the treatment is converted to non-ergot dopamine agonists.
18560792|t|Valvular heart disease in patients with Parkinson's disease treated with pergolide. Course following treatment modifications.
18560792	0	22	Valvular heart disease	Disease	D006349
18560792	40	59	Parkinson's disease	Disease	D010300
18560792	73	82	pergolide	Chemical	D010479
18560792	126	154	Valvular heart abnormalities	Disease	D006349
18560792	191	210	Parkinson's disease	Disease	D010300
18560792	212	214	PD	Disease	D010300
18560792	229	238	pergolide	Chemical	D010479
18560792	455	481	valvular heart abnormality	Disease	D006349
18560792	573	575	PD	Disease	D010300
18560792	617	626	pergolide	Chemical	D010479
18560792	724	726	PD	Disease	D010300
18560792	838	847	pergolide	Chemical	D010479
18560792	915	917	PD	Disease	D010300
18560792	997	1017	aortic regurgitation	Disease	D001022
18560792	1049	1069	mitral regurgitation	Disease	D008944
18560792	1119	1121	PD	Disease	D010300
18560792	1298	1307	pergolide	Chemical	D010479
18560792	1365	1374	pergolide	Chemical	D010479
18560792	1417	1439	valvular regurgitation	Disease	D006349
18560792	1467	1476	pergolide	Chemical	D010479
18560792	1534	1547	heart failure	Disease	D006333
18560792	1549	1558	Pergolide	Chemical	D010479
18560792	1596	1618	valvular heart disease	Disease	D006349
18560792	1741	1754	heart failure	Disease	D006333
18560792	1857	1876	valve regurgitation	Disease	D006349
18560792	1880	1882	PD	Disease	D010300
18560792	1905	1914	pergolide	Chemical	D010479
18560792	2012	2020	dopamine	Chemical	D004298
18560792	induced	D010479	D001022
18560792	induced	D010479	D008944
18560792	induced	D010479	D006333
18560792	treated	D004298	D010300
18560792	induced	D010479	D006349
18560792	treated	D010479	D010300
1867351|a|This study describes neuropsychiatric side effects in patients after treatment with mefloquine. Reactions consisted mainly of seizures, acute psychoses, anxiety neurosis, and major disturbances of sleep-wake rhythm. Side effects occurred after both therapeutic and prophylactic intake and were graded from moderate to severe. In a risk analysis of neuropsychiatric side effects in Germany, it is estimated that one of 8,000 mefloquine users suffers from such reactions. The incidence calculation revealed that one of 215 therapeutic users had reactions, compared with one of 13,000 in the prophylaxis group, making the risk of neuropsychiatric reactions after mefloquine treatment 60 times higher than after prophylaxis. Therefore, certain limitations for malaria prophylaxis and treatment with mefloquine are recommended.
1867351|t|Neuropsychiatric side effects after the use of mefloquine.
1867351	47	57	mefloquine	Chemical	D015767
1867351	143	153	mefloquine	Chemical	D015767
1867351	185	193	seizures	Disease	D012640
1867351	201	210	psychoses	Disease	D011605
1867351	212	228	anxiety neurosis	Disease	D001008
1867351	240	273	disturbances of sleep-wake rhythm	Disease	D012893
1867351	483	493	mefloquine	Chemical	D015767
1867351	719	729	mefloquine	Chemical	D015767
1867351	815	822	malaria	Disease	D008288
1867351	854	864	mefloquine	Chemical	D015767
1867351	induced	D015767	D012640
1867351	induced	D015767	D011605
1867351	induced	D015767	D001008
1867351	induced	D015767	D012893
1867351	treated	D015767	D008288
18726058|a|BACKGROUND: Papaverine hydrochloride is a direct-acting vasodilator used to manage vasospasm during various neurosurgical operations. Transient cranial nerve dysfunction has been described in a few cases with topical papaverine. This study supports previous reports and provides neurophysiological evidence of an adverse effect on the auditory nerve. METHODS: We conducted a retrospective review of 70 consecutive microvascular decompression operations and studied those patients who received topical papaverine for vasospasm. Topical papaverine was used as a direct therapeutic action to manage vasospasm in a total of 11 patients. The timing of papaverine application and ongoing operative events was reviewed relative to changes in neurophysiological recordings. Brainstem auditory evoked potentials (BAEPs) were routinely used to monitor cochlear nerve function during these operations. FINDINGS: A temporal relationship was found between topical papaverine and BAEP changes leading to complete waveform loss. The average temporal delay between papaverine and the onset of an adverse BAEP change was 5 min. In 10 of 11 patients, BAEP waves II/III-V completely disappeared within 2 to 25 min after papaverine. Eight of these 10 patients had complete loss of BAEP waveforms within 10 min. One patient showed no recovery of later waves and a delayed profound sensorineural hearing loss. The average recovery time of BAEP waveforms to pre-papaverine baseline values was 39 min. CONCLUSIONS: Topical papaverine for the treatment of vasospasm was associated with the onset of a transient disturbance in neurophysiological function of the ascending auditory brainstem pathway. The complete disappearance of BAEP waveforms with a consistent temporal delay suggests a possible adverse effect on the proximal eighth nerve. Recommendations to avoid potential cranial nerve deficits from papaverine are provided.
18726058|t|Adverse effects of topical papaverine on auditory nerve function.
18726058	27	37	papaverine	Chemical	D010208
18726058	78	102	Papaverine hydrochloride	Chemical	D010208
18726058	149	158	vasospasm	Disease	D020301
18726058	210	235	cranial nerve dysfunction	Disease	D003389
18726058	283	293	papaverine	Chemical	D010208
18726058	567	577	papaverine	Chemical	D010208
18726058	582	591	vasospasm	Disease	D020301
18726058	601	611	papaverine	Chemical	D010208
18726058	662	671	vasospasm	Disease	D020301
18726058	713	723	papaverine	Chemical	D010208
18726058	1017	1027	papaverine	Chemical	D010208
18726058	1115	1125	papaverine	Chemical	D010208
18726058	1267	1277	papaverine	Chemical	D010208
18726058	1426	1452	sensorineural hearing loss	Disease	D006319
18726058	1505	1515	papaverine	Chemical	D010208
18726058	1565	1575	papaverine	Chemical	D010208
18726058	1597	1606	vasospasm	Disease	D020301
18726058	1838	1881	adverse effect on the proximal eighth nerve	Disease	D000160
18726058	1918	1940	cranial nerve deficits	Disease	D003389
18726058	1946	1956	papaverine	Chemical	D010208
18726058	treated	D010208	D020301
18726058	induced	D010208	D003389
18726058	induced	D010208	D006319
18726058	induced	D010208	D000160
18754075|a|A 61-year-old Japanese man with nephrotic syndrome due to focal segmental glomerulosclerosis was initially responding well to steroid therapy. The amount of daily urinary protein decreased from 15.6 to 2.8 g. Within 14 days of the oral bisphosphonate (alendronate sodium) administration, the amount of daily urinary protein increased rapidly up to 12.8 g with acute renal failure. After discontinuing the oral alendronate, the patient underwent six cycles of hemodialysis and four cycles of LDL apheresis. Urinary volume and serum creatinine levels recovered to the normal range, with urinary protein disappearing completely within 40 days. This report demonstrates that not only intravenous, but also oral bisphosphonates can aggravate proteinuria and acute renal failure.
18754075|t|Massive proteinuria and acute renal failure after oral bisphosphonate (alendronate) administration in a patient with focal segmental glomerulosclerosis.
18754075	8	19	proteinuria	Disease	D011507
18754075	24	43	acute renal failure	Disease	D058186
18754075	55	69	bisphosphonate	Chemical	D004164
18754075	71	82	alendronate	Chemical	D019386
18754075	117	151	focal segmental glomerulosclerosis	Disease	D005923
18754075	185	203	nephrotic syndrome	Disease	D009404
18754075	211	245	focal segmental glomerulosclerosis	Disease	D005923
18754075	279	286	steroid	Chemical	D013256
18754075	389	403	bisphosphonate	Chemical	D004164
18754075	405	423	alendronate sodium	Chemical	D019386
18754075	513	532	acute renal failure	Disease	D058186
18754075	563	574	alendronate	Chemical	D019386
18754075	684	694	creatinine	Chemical	D003404
18754075	860	875	bisphosphonates	Chemical	D004164
18754075	890	901	proteinuria	Disease	D011507
18754075	906	925	acute renal failure	Disease	D058186
18754075	induced	D004164	D011507
18754075	induced	D019386	D011507
18754075	induced	D004164	D058186
18754075	induced	D019386	D058186
18754075	treated	D013256	D009404
18754075	treated	D013256	D005923
18951540|a|In a placebo-controlled, single-blinded, crossover study, we assessed the effect of "real" repetitive transcranial magnetic stimulation (rTMS) versus "sham" rTMS (placebo) on peak dose dyskinesias in patients with Parkinson's disease (PD). Ten patients with PD and prominent dyskinesias had rTMS (1,800 pulses; 1 Hz rate) delivered over the motor cortex for 4 consecutive days twice, once real stimuli and once sham stimulation were used; evaluations were done at the baseline and 1 day after the end of each of the treatment series. Direct comparison between sham and real rTMS effects showed no significant difference in clinician-assessed dyskinesia severity. However, comparison with the baseline showed small but significant reduction in dyskinesia severity following real rTMS but not placebo. The major effect was on dystonia subscore. Similarly, in patient diaries, although both treatments caused reduction in subjective dyskinesia scores during the days of intervention, the effect was sustained for 3 days after the intervention for the real rTMS only. Following rTMS, no side effects and no adverse effects on motor function and PD symptoms were noted. The results suggest the existence of residual beneficial clinical aftereffects of consecutive daily applications of low-frequency rTMS on dyskinesias in PD. The effects may be further exploited for potential therapeutic uses.
18951540|t|Repetitive transcranial magnetic stimulation for levodopa-induced dyskinesias in Parkinson's disease.
18951540	49	57	levodopa	Chemical	D007980
18951540	66	77	dyskinesias	Disease	D004409
18951540	81	100	Parkinson's disease	Disease	D010300
18951540	287	298	dyskinesias	Disease	D004409
18951540	316	335	Parkinson's disease	Disease	D010300
18951540	337	339	PD	Disease	D010300
18951540	360	362	PD	Disease	D010300
18951540	377	388	dyskinesias	Disease	D004409
18951540	744	754	dyskinesia	Disease	D004409
18951540	845	855	dyskinesia	Disease	D004409
18951540	926	934	dystonia	Disease	D004421
18951540	1032	1042	dyskinesia	Disease	D004409
18951540	1243	1245	PD	Disease	D010300
18951540	1405	1416	dyskinesias	Disease	D004409
18951540	1420	1422	PD	Disease	D010300
18951540	induced	D007980	D004409
18951540	treated	D007980	D010300
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|t|Ifosfamide continuous infusion without mesna. A phase I trial of a 14-day cycle.
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	induced	D007069	D009325
1899352	induced	D007069	D007970
1899352	induced	D007069	D006417
1899352	induced	D007069	D064420
1899352	induced	D007069	D003221
18996674|a|Priapism is the prolonged erection of the penis in the absence of sexual arousal. A 45-year-old man, an admitted frequent cocaine user, presented to the Emergency Department (ED) on two separate occasions with a history of priapism after cocaine use. The management options in the ED, as exemplified by four individual case reports, in particular the use of a minimally invasive method of intracorporal epinephrine instillation, are discussed.
18996674|t|Intracavernous epinephrine: a minimally invasive treatment for priapism in the emergency department.
18996674	15	26	epinephrine	Chemical	D004837
18996674	63	71	priapism	Disease	D011317
18996674	101	109	Priapism	Disease	D011317
18996674	223	230	cocaine	Chemical	D003042
18996674	324	332	priapism	Disease	D011317
18996674	339	346	cocaine	Chemical	D003042
18996674	504	515	epinephrine	Chemical	D004837
18996674	treated	D004837	D011317
18996674	induced	D003042	D011317
19269743|a|Pain memory is thought to affect future pain sensitivity and thus contribute to clinical pain conditions. Systematic investigations of the human capacity to remember sensory features of experimental pain are sparse. In order to address long-term pain memory, nine healthy male volunteers received intradermal injections of three doses of capsaicin (0.05, 1 and 20 microg, separated by 15 min breaks), each given three times in a balanced design across three sessions at one week intervals. Pain rating was performed using a computerized visual analogue scale (0-100) digitized at 1/s, either immediately online or one hour or one day after injection. Subjects also recalled their pains one week later. Capsaicin injection reliably induced a dose-dependent flare (p<0.001) without any difference within or across sessions. The strong burning pain decayed exponentially within a few minutes. Subjects were able to reliably discriminate pain magnitude and duration across capsaicin doses (both p<0.001), regardless of whether first-time ratings were requested immediately, after one hour or after one day. Pain recall after one week was similarly precise (magnitude: p<0.01, duration: p<0.05). Correlation with rating recall after one week was best when first-time ratings were requested as late as one day after injection (R(2)=0.79) indicating that both rating retrievals utilized similar memory traces. These results indicate a reliable memory for magnitude and duration of experimentally induced pain. The data further suggest that the consolidation of this memory is an important interim stage, and may take up to one day.
19269743|t|Explicit episodic memory for sensory-discriminative components of capsaicin-induced pain: immediate and delayed ratings.
19269743	66	75	capsaicin	Chemical	D002211
19269743	84	88	pain	Disease	D010146
19269743	121	125	Pain	Disease	D010146
19269743	161	165	pain	Disease	D010146
19269743	210	214	pain	Disease	D010146
19269743	320	324	pain	Disease	D010146
19269743	367	371	pain	Disease	D010146
19269743	459	468	capsaicin	Chemical	D002211
19269743	611	615	Pain	Disease	D010146
19269743	801	806	pains	Disease	D010146
19269743	823	832	Capsaicin	Chemical	D002211
19269743	962	966	pain	Disease	D010146
19269743	1055	1059	pain	Disease	D010146
19269743	1090	1099	capsaicin	Chemical	D002211
19269743	1224	1228	Pain	Disease	D010146
19269743	1618	1622	pain	Disease	D010146
19269743	induced	D002211	D010146
19299179|a|Pneumocystis pneumonia (PCP), a common opportunistic infection in HIV-infected individuals, is generally treated with high doses of co-trimoxazole. However, treatment is often limited by adverse effects. Here, we report two cases of severely immunocompromised HIV-infected patients who developed severe intrahepatic cholestasis, and in one patient lesions mimicking liver abscess formation on radiologic exams, during co-trimoxazole treatment for PCP. Whereas patient 1 showed lesions of up to 1 cm readily detectable on magnetic resonance imaging under prolonged co-trimoxazole treatment, therapy of patient 2 was switched early.
19299179|t|Severe and long lasting cholestasis after high-dose co-trimoxazole treatment for Pneumocystis pneumonia in HIV-infected patients--a report of two cases.
19299179	24	35	cholestasis	Disease	D002779
19299179	52	66	co-trimoxazole	Chemical	D015662
19299179	81	103	Pneumocystis pneumonia	Disease	D011020
19299179	107	119	HIV-infected	Disease	D015658
19299179	153	175	Pneumocystis pneumonia	Disease	D011020
19299179	177	180	PCP	Disease	D011020
19299179	192	215	opportunistic infection	Disease	D009894
19299179	219	231	HIV-infected	Disease	D015658
19299179	285	299	co-trimoxazole	Chemical	D015662
19299179	413	425	HIV-infected	Disease	D015658
19299179	456	480	intrahepatic cholestasis	Disease	D002780
19299179	519	532	liver abscess	Disease	D008100
19299179	571	585	co-trimoxazole	Chemical	D015662
19299179	600	603	PCP	Disease	D011020
19299179	717	731	co-trimoxazole	Chemical	D015662
19299179	induced	D015662	D002779
19299179	treated	D015662	D011020
19299179	treated	D015662	D015658
19299179	induced	D015662	D002780
19299179	treated	D015662	D009894
19308880|a|INTRODUCTION: Confusion is an adverse drug reaction frequently observed with valproic acid. Some case reports are published in the literature but no systematic study from a sample of patients has been published. We performed this study in order to describe the main characteristics of this adverse drug reaction. METHODS: Using the French Pharmacovigilance database, we selected the cases of confusion reported since 1985 with valproic acid. RESULTS: 272 cases of confusion were reported with valproic acid: 153 women and 119 men. Confusion mostly occurred during the two first weeks following valproic acid exposure (39.7%). It was "serious" for almost 2/3 of the patients (62.5%) and its outcome favourable in most of the cases (82%). The occurrence of this ADR was more frequent in patients aged between 61 and 80 years. CONCLUSION: This work shows that confusion with valproic acid is a serious, rather frequent but reversible adverse drug reaction. It occurs especially in older patients and during the first two weeks of treatment.
19308880|t|Confusion, a rather serious adverse drug reaction with valproic acid: a review of the French Pharmacovigilance database.
19308880	0	9	Confusion	Disease	D003221
19308880	55	68	valproic acid	Chemical	D014635
19308880	135	144	Confusion	Disease	D003221
19308880	198	211	valproic acid	Chemical	D014635
19308880	513	522	confusion	Disease	D003221
19308880	548	561	valproic acid	Chemical	D014635
19308880	585	594	confusion	Disease	D003221
19308880	614	627	valproic acid	Chemical	D014635
19308880	652	661	Confusion	Disease	D003221
19308880	715	728	valproic acid	Chemical	D014635
19308880	978	987	confusion	Disease	D003221
19308880	993	1006	valproic acid	Chemical	D014635
19308880	induced	D014635	D003221
19631624|a|It has been consistently shown that ecstasy users display impairments in learning and memory performance. In addition, working memory processing in ecstasy users has been shown to be associated with neural alterations in hippocampal and/or cortical regions as measured by functional magnetic resonance imaging (fMRI). Using functional imaging and a face-learning task, we investigated neural correlates of encoding and recalling face-name associations in 20 recreational drug users whose predominant drug use was ecstasy and 20 controls. To address the potential confounding effects of the cannabis use of the ecstasy using group, a second analysis included 14 previously tested cannabis users (Nestor, L., Roberts, G., Garavan, H., Hester, R., 2008. Deficits in learning and memory: parahippocampal hyperactivity and frontocortical hypoactivity in cannabis users. Neuroimage 40, 1328-1339). Ecstasy users performed significantly worse in learning and memory compared to controls and cannabis users. A conjunction analysis of the encode and recall phases of the task revealed ecstasy-specific hyperactivity in bilateral frontal regions, left temporal, right parietal, bilateral temporal, and bilateral occipital brain regions. Ecstasy-specific hypoactivity was evident in the right dorsal anterior cingulated cortex (ACC) and left posterior cingulated cortex. In both ecstasy and cannabis groups brain activation was decreased in the right medial frontal gyrus, left parahippocampal gyrus, left dorsal cingulate gyrus, and left caudate. These results elucidated ecstasy-related deficits, only some of which might be attributed to cannabis use. These ecstasy-specific effects may be related to the vulnerability of isocortical and allocortical regions to the neurotoxic effects of ecstasy.
19631624|t|Learning and memory deficits in ecstasy users and their neural correlates during a face-learning task.
19631624	0	28	Learning and memory deficits	Disease	-1
19631624	0	17	Learning deficits	Disease	D007859
19631624	13	28	memory deficits	Disease	D008569
19631624	20	37	Learning deficits	Disease	D007859
19631624	32	39	ecstasy	Chemical	D018817
19631624	139	146	ecstasy	Chemical	D018817
19631624	161	195	impairments in learning and memory	Disease	-1
19631624	161	184	impairments in learning	Disease	D007859
19631624	161	182	impairments in memory	Disease	D008569
19631624	189	210	impairments in memory	Disease	D008569
19631624	251	258	ecstasy	Chemical	D018817
19631624	616	623	ecstasy	Chemical	D018817
19631624	693	701	cannabis	Chemical	D002188
19631624	713	720	ecstasy	Chemical	D018817
19631624	782	790	cannabis	Chemical	D002188
19631624	854	885	Deficits in learning and memory	Disease	-1
19631624	854	874	Deficits in learning	Disease	D007859
19631624	854	872	Deficits in memory	Disease	D008569
19631624	879	897	Deficits in memory	Disease	D008569
19631624	903	916	hyperactivity	Disease	D006948
19631624	952	960	cannabis	Chemical	D002188
19631624	995	1002	Ecstasy	Chemical	D018817
19631624	1087	1095	cannabis	Chemical	D002188
19631624	1179	1186	ecstasy	Chemical	D018817
19631624	1196	1209	hyperactivity	Disease	D006948
19631624	1330	1337	Ecstasy	Chemical	D018817
19631624	1471	1478	ecstasy	Chemical	D018817
19631624	1483	1491	cannabis	Chemical	D002188
19631624	1665	1672	ecstasy	Chemical	D018817
19631624	1733	1741	cannabis	Chemical	D002188
19631624	1753	1760	ecstasy	Chemical	D018817
19631624	1861	1871	neurotoxic	Disease	D020258
19631624	1883	1890	ecstasy	Chemical	D018817
19631624	Association	D002188	-1
19631624	Association	D002188	D006948
19631624	induced	D018817	D006948
19631624	Association	D018817	D020258
19631624	induced	D018817	-1
1967484|a|Sulpiride is a selective D2-receptor antagonist with antipsychotic and antidepressant properties. Although initially thought to be free of extrapyramidal side effects, sulpiride-induced tardive dyskinesia and parkinsonism have been reported occasionally. We studied a 37-year-old man who developed persistent segmental dystonia within 2 months after starting sulpiride therapy. We could not find any previous reports of sulpiride-induced tardive dystonia.
1967484|t|Sulpiride-induced tardive dystonia.
1967484	0	9	Sulpiride	Chemical	D013469
1967484	18	34	tardive dystonia	Disease	D004421
1967484	36	45	Sulpiride	Chemical	D013469
1967484	107	121	antidepressant	Chemical	D000928
1967484	204	213	sulpiride	Chemical	D013469
1967484	222	240	tardive dyskinesia	Disease	D004409
1967484	245	257	parkinsonism	Disease	D010302
1967484	355	363	dystonia	Disease	D004421
1967484	395	404	sulpiride	Chemical	D013469
1967484	456	465	sulpiride	Chemical	D013469
1967484	474	490	tardive dystonia	Disease	D004421
1967484	induced	D013469	D004421
1967484	induced	D013469	D004409
1967484	induced	D013469	D010302
19820426|a|We report twin neonates who were born prematurely at 32 weeks of gestation to a mother with human immunodeficiency virus infection. One of the twins developed complete heart block and dilated cardiomyopathy related to lopinavir/ritonavir therapy, a boosted protease-inhibitor agent, while the other twin developed mild bradycardia. We recommend caution in the use of lopinavir/ritonavir in the immediate neonatal period.
19820426|t|Twin preterm neonates with cardiac toxicity related to lopinavir/ritonavir therapy.
19820426	27	43	cardiac toxicity	Disease	D066126
19820426	55	74	lopinavir/ritonavir	Chemical	C558899
19820426	176	214	human immunodeficiency virus infection	Disease	D015658
19820426	252	263	heart block	Disease	D006327
19820426	268	290	dilated cardiomyopathy	Disease	D002311
19820426	302	321	lopinavir/ritonavir	Chemical	C558899
19820426	403	414	bradycardia	Disease	D001919
19820426	451	470	lopinavir/ritonavir	Chemical	C558899
19820426	induced	C558899	D066126
19820426	treated	C558899	D015658
19820426	induced	C558899	D006327
19820426	induced	C558899	D002311
19820426	induced	C558899	D001919
1987816|a|OBJECTIVE: This study was designed to determine whether patients maintained on a regimen of lithium on a once-per-day schedule have lower urine volumes than do patients receiving multiple doses per day. METHOD: This was a cross-sectional study of 85 patients from a lithium clinic who received different dose schedules. Patients were admitted to the hospital for measurement of lithium level, creatinine clearance, urine volume, and maximum osmolality. RESULTS: Multiple daily doses of lithium were associated with higher urine volumes. The dosing schedule, duration of lithium treatment, and daily dose of lithium did not affect maximum osmolality or creatinine clearance. CONCLUSIONS: Urine volume can be reduced by giving lithium once daily and/or by lowering the total daily dose. Lithium-induced polyuria seems to be related to extrarenal as well as to renal effects.
1987816|t|Less frequent lithium administration and lower urine volume.
1987816	14	21	lithium	Chemical	D008094
1987816	153	160	lithium	Chemical	D008094
1987816	327	334	lithium	Chemical	D008094
1987816	439	446	lithium	Chemical	D008094
1987816	454	464	creatinine	Chemical	D003404
1987816	547	554	lithium	Chemical	D008094
1987816	631	638	lithium	Chemical	D008094
1987816	668	675	lithium	Chemical	D008094
1987816	713	723	creatinine	Chemical	D003404
1987816	786	793	lithium	Chemical	D008094
1987816	846	853	Lithium	Chemical	D008094
1987816	862	870	polyuria	Disease	D011141
1987816	induced	D008094	D011141
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|t|Reversible myocardial hypertrophy induced by tacrolimus in a pediatric heart transplant recipient: case report.
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	induced	D016559	D066126
19917396	induced	D016559	D006332
19917396	induced	D016559	D006984
19917396	induced	D016559	D004487
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|t|Nimodipine prevents memory impairment caused by nitroglycerin-induced hypotension in adult mice.
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	treated	D009553	D007022
19923525	induced	D005996	D007022
19923525	treated	D009553	D003072
19923525	induced	D005996	D003072
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|t|A novel animal model to evaluate the ability of a drug delivery system to promote the passage through the BBB.
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	induced	D013619	D001930
19944736	induced	D013619	D004827
19944736	induced	D013619	D012640
19957053|a|BACKGROUND: Vasopressor agents are used to correct anesthesia-induced hypotension. We describe the effect of phenylephrine and ephedrine on frontal lobe oxygenation (S(c)O(2)) following anesthesia-induced hypotension. METHODS: Following induction of anesthesia by fentanyl (0.15 mg kg(-1)) and propofol (2.0 mg kg(-1)), 13 patients received phenylephrine (0.1 mg iv) and 12 patients received ephedrine (10 mg iv) to restore mean arterial pressure (MAP). Heart rate (HR), MAP, stroke volume (SV), cardiac output (CO), and frontal lobe oxygenation (S(c)O(2)) were registered. RESULTS: Induction of anesthesia was followed by a decrease in MAP, HR, SV, and CO concomitant with an elevation in S(c)O(2). After administration of phenylephrine, MAP increased (51 +/- 12 to 81 +/- 13 mmHg; P < 0.001; mean +/- SD). However, a 14% (from 70 +/- 8% to 60 +/- 7%) reduction in S(c)O(2) (P < 0.05) followed with no change in CO (3.7 +/- 1.1 to 3.4 +/- 0.9 l min(-1)). The administration of ephedrine led to a similar increase in MAP (53 +/- 9 to 79 +/- 8 mmHg; P < 0.001), restored CO (3.2 +/- 1.2 to 5.0 +/- 1.3 l min(-1)), and preserved S(c)O(2). CONCLUSIONS: The utilization of phenylephrine to correct hypotension induced by anesthesia has a negative impact on S(c)O(2) while ephedrine maintains frontal lobe oxygenation potentially related to an increase in CO.
19957053|t|Phenylephrine but not ephedrine reduces frontal lobe oxygenation following anesthesia-induced hypotension.
19957053	0	13	Phenylephrine	Chemical	D010656
19957053	22	31	ephedrine	Chemical	D004809
19957053	32	64	reduces frontal lobe oxygenation	Disease	D002534
19957053	94	105	hypotension	Disease	D007022
19957053	177	188	hypotension	Disease	D007022
19957053	216	229	phenylephrine	Chemical	D010656
19957053	234	243	ephedrine	Chemical	D004809
19957053	312	323	hypotension	Disease	D007022
19957053	371	379	fentanyl	Chemical	D005283
19957053	401	409	propofol	Chemical	D015742
19957053	448	461	phenylephrine	Chemical	D010656
19957053	499	508	ephedrine	Chemical	D004809
19957053	583	589	stroke	Disease	D020521
19957053	730	763	a decrease in MAP, HR, SV, and CO	Disease	D007022|D002303
19957053	730	747	a decrease in MAP	Disease	D007022
19957053	730	746	a decrease in CO	Disease	D002303
19957053	761	777	a decrease in CO	Disease	D002303
19957053	831	844	phenylephrine	Chemical	D010656
19957053	1085	1094	ephedrine	Chemical	D004809
19957053	1276	1289	phenylephrine	Chemical	D010656
19957053	1301	1312	hypotension	Disease	D007022
19957053	1375	1384	ephedrine	Chemical	D004809
19957053	treated	D010656	D002534
19957053	treated	D010656	D007022
19957053	treated	D004809	D007022
19957053	induced	D005283	D007022
19957053	induced	D015742	D007022
20084309|a|BACKGROUND: TEE is a semi-invasive tool broadly used and its utilization associated to sedatives drugs might to affect the procedure safety. OBJECTIVE: to analyze aspects of TEE safety associated to the use of Midazolan (MZ) and Flumazenil (FL) and the influence of the clinical variables on the event rate. METHOD: prospective study with 137 patients that underwent TEE with MZ associated to moderate sedation. We analyzed the following events: complications related with the topical anesthesia, with MZ use and with the procedure. Uni- and multivariate analyses were used to test the influence of the clinical variables: age, sex, stroke, myocardiopathy (MP), duration of the test, mitral regurgitation (MR) and the MZ dose. RESULTS: All patients (65+/-16 yrs; 58% males) finished the examination. The mean doses of MZ and FL were 4.3+/-1.9 mg and 0.28+/-0.2 mg, respectively. The duration of the examination and the mean ejection fraction (EF) were 16.4+/-6.1 minutes and 60+/-9%, respectively. Mild hypoxia (SO2<90%) was the most common event (11 patients); 3 patients (2%) presented transient hypoxia due to upper airway obstruction by probe introduction and 8 (5.8%) due to hypoxia caused by MZ use. Transient hypotension (SAP<90mmHg) occurred in 1 patient (0.7%). The multivariate analysis showed that severe MR, MP (EF<45%) and high doses of MZ (>5mg) were associated with events (p<0.001). The EF was 40%, in the group with MP and 44% in the group with severe MR and it can be a factor associated with clinical events in the last group. CONCLUSION: TEE with sedation presents a low rate of events. There were no severe events and there was no need to interrupt the examinations.
20084309|t|Safety of transesophageal echocardiography in adults: study in a multidisciplinary hospital.
20084309	303	312	Midazolan	Chemical	D008874
20084309	314	316	MZ	Chemical	D008874
20084309	322	332	Flumazenil	Chemical	D005442
20084309	334	336	FL	Chemical	D005442
20084309	469	471	MZ	Chemical	D008874
20084309	595	597	MZ	Chemical	D008874
20084309	726	732	stroke	Disease	D020521
20084309	734	748	myocardiopathy	Disease	D009202
20084309	750	752	MP	Disease	D009202
20084309	777	797	mitral regurgitation	Disease	D008944
20084309	799	801	MR	Disease	D008944
20084309	811	813	MZ	Chemical	D008874
20084309	911	913	MZ	Chemical	D008874
20084309	918	920	FL	Chemical	D005442
20084309	1096	1103	hypoxia	Disease	D000860
20084309	1191	1198	hypoxia	Disease	D000860
20084309	1212	1230	airway obstruction	Disease	D000402
20084309	1273	1280	hypoxia	Disease	D000860
20084309	1291	1293	MZ	Chemical	D008874
20084309	1309	1320	hypotension	Disease	D007022
20084309	1409	1411	MR	Disease	D008944
20084309	1413	1415	MP	Disease	D009202
20084309	1443	1445	MZ	Chemical	D008874
20084309	1526	1528	MP	Disease	D009202
20084309	1562	1564	MR	Disease	D008944
20084309	induced	D008874	D000402
20084309	induced	D008874	D000860
20084309	induced	D008874	D007022
20098969|a|AIM: The aim of the documentation of this clinical case is to make clinicians aware of "meth mouth" and the medical risks associated with this serious condition. BACKGROUND: Methamphetamine is a very addictive, powerful stimulant that increases wakefulness and physical activity and can produce other effects such as cardiac dysrhythmias, hypertension, hallucinations, and violent behavior. Dental patients abusing methamphetamine can present with poor oral hygiene, xerostomia, rampant caries ("meth mouth"), and excessive tooth wear. Oral rehabilitation of patients using methamphetamine can be challenging. CASE DESCRIPTION: A 30-year-old Caucasian woman presented with dental pain, bad breath, and self-reported poor esthetics. A comprehensive examination including her medical history, panoramic radiograph, and intraoral examination revealed 19 carious lesions, which is not very common for a healthy adult. She reported her use of methamphetamine for five years and had not experienced any major carious episodes before she started using the drug. SUMMARY: The patient's medical and dental histories along with radiographic and clinical findings lead to a diagnosis of "meth mouth." Although three different dental treatment modalities (either conventional or implant-supported) have been offered to the patient since August 2007, the patient has yet to initiate any treatment. CLINICAL SIGNIFICANCE: This clinical case showing oral manifestations of meth mouth was presented to help dental practitioners recognize and manage patients who may be abusing methamphetamines. Dental practitioners also may be skeptical about the reliability of appointment keeping by these patients, as they frequently miss their appointments without reasonable justification.
20098969|t|Oral manifestations of "meth mouth": a case report.
20098969	24	34	meth mouth	Disease	-1
20098969	140	150	meth mouth	Disease	-1
20098969	226	241	Methamphetamine	Chemical	D008694
20098969	369	389	cardiac dysrhythmias	Disease	D001145
20098969	391	403	hypertension	Disease	D006973
20098969	405	419	hallucinations	Disease	D006212
20098969	425	441	violent behavior	Disease	D001523
20098969	467	482	methamphetamine	Chemical	D008694
20098969	519	529	xerostomia	Disease	D014987
20098969	539	545	caries	Disease	D003731
20098969	548	558	meth mouth	Disease	-1
20098969	576	586	tooth wear	Disease	D057085
20098969	626	641	methamphetamine	Chemical	D008694
20098969	732	736	pain	Disease	D010146
20098969	738	748	bad breath	Disease	D012120
20098969	903	918	carious lesions	Disease	D003731
20098969	990	1005	methamphetamine	Chemical	D008694
20098969	1055	1071	carious episodes	Disease	D003731
20098969	1229	1239	meth mouth	Disease	-1
20098969	1510	1520	meth mouth	Disease	-1
20098969	1613	1629	methamphetamines	Chemical	D008694
20098969	induced	D008694	-1
20098969	induced	D008694	D057085
20098969	induced	D008694	D010146
20098969	induced	D008694	D012120
20098969	induced	D008694	D003731
20098969	induced	D008694	D001145
20098969	induced	D008694	D006973
20098969	induced	D008694	D006212
20098969	induced	D008694	D001523
20098969	induced	D008694	D014987
20520283|a|Asenapine is approved by the Food and Drugs Administration in adults for acute treatment of schizophrenia or of manic or mixed episodes associated with bipolar I disorder with or without psychotic features. In a double-blind 6-week trial, 458 patients with acute schizophrenia were randomly assigned to fixed-dose treatment with asenapine at 5 mg twice daily (BID), asenapine at 10 mg BID, placebo, or haloperidol at 4 mg BID (to verify assay sensitivity). With last observations carried forward (LOCF), mean Positive and Negative Syndrome Scale total score reductions from baseline to endpoint were significantly greater with asenapine at 5 mg BID (-16.2) and haloperidol (-15.4) than placebo (-10.7; both P < 0.05); using mixed model for repeated measures (MMRM), changes at day 42 were significantly greater with asenapine at 5 and 10 mg BID (-21.3 and -19.4, respectively) and haloperidol (-20.0) than placebo (-14.6; all P < 0.05). On the Positive and Negative Syndrome Scale positive subscale, all treatments were superior to placebo with LOCF and MMRM; asenapine at 5 mg BID was superior to placebo on the negative subscale with MMRM and on the general psychopathology subscale with LOCF and MMRM. Treatment-related adverse events (AEs) occurred in 44% and 52%, 57%, and 41% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Extrapyramidal symptoms reported as AEs occurred in 15% and 18%, 34%, and 10% of the asenapine at 5 and 10 mg BID, haloperidol, and placebo groups, respectively. Across all groups, no more than 5% of patients had clinically significant weight change. Post hoc analyses indicated that efficacy was similar with asenapine and haloperidol; greater contrasts were seen in AEs, especially extrapyramidal symptoms.
20520283|t|Efficacy and safety of asenapine in a placebo- and haloperidol-controlled trial in patients with acute exacerbation of schizophrenia.
20520283	23	32	asenapine	Chemical	C522667
20520283	51	62	haloperidol	Chemical	D006220
20520283	119	132	schizophrenia	Disease	D012559
20520283	134	143	Asenapine	Chemical	C522667
20520283	226	239	schizophrenia	Disease	D012559
20520283	246	251	manic	Disease	D001714
20520283	286	304	bipolar I disorder	Disease	D001714
20520283	321	330	psychotic	Disease	D011618
20520283	397	410	schizophrenia	Disease	D012559
20520283	463	472	asenapine	Chemical	C522667
20520283	500	509	asenapine	Chemical	C522667
20520283	536	547	haloperidol	Chemical	D006220
20520283	761	770	asenapine	Chemical	C522667
20520283	795	806	haloperidol	Chemical	D006220
20520283	950	959	asenapine	Chemical	C522667
20520283	1015	1026	haloperidol	Chemical	D006220
20520283	1194	1203	asenapine	Chemical	C522667
20520283	1423	1432	asenapine	Chemical	C522667
20520283	1453	1464	haloperidol	Chemical	D006220
20520283	1500	1523	Extrapyramidal symptoms	Disease	D001480
20520283	1585	1594	asenapine	Chemical	C522667
20520283	1615	1626	haloperidol	Chemical	D006220
20520283	1810	1819	asenapine	Chemical	C522667
20520283	1824	1835	haloperidol	Chemical	D006220
20520283	1884	1907	extrapyramidal symptoms	Disease	D001480
20520283	treated	D006220	D012559
20520283	treated	D006220	D011618
20520283	induced	C522667	D001480
20520283	induced	D006220	D001480
20520283	treated	C522667	D012559
20520283	treated	C522667	D001714
20520283	treated	C522667	D011618
2054792|a|Thermal enhancement of Adriamycin-mediated antitumor activity and normal tissue toxicities by whole body hyperthermia were compared using a F344 rat model. Antitumor activity was studied using a tumor growth delay assay. Acute normal tissue toxicities (i.e., leukopenia and thrombocytopenia) and late normal tissue toxicities (i.e., myocardial and kidney injury) were evaluated by functional/physiological assays and by morphological techniques. Whole body hyperthermia (120 min at 41.5 degrees C) enhanced both Adriamycin-mediated antitumor activity and toxic side effects. The thermal enhancement ratio calculated for antitumor activity was 1.6. Thermal enhancement ratios estimated for "acute" hematological changes were 1.3, whereas those estimated for "late" damage (based on morphological cardiac and renal lesions) varied between 2.4 and 4.3. Thus, while whole body hyperthermia enhances Adriamycin-mediated antitumor effect, normal tissue toxicity is also increased, and the potential therapeutic gain of the combined modality treatment is eroded.
2054792|t|Effect of adriamycin combined with whole body hyperthermia on tumor and normal tissues.
2054792	10	20	adriamycin	Chemical	D004317
2054792	46	58	hyperthermia	Disease	D005334
2054792	62	67	tumor	Disease	D009369
2054792	111	121	Adriamycin	Chemical	D004317
2054792	168	178	toxicities	Disease	D064420
2054792	193	205	hyperthermia	Disease	D005334
2054792	283	288	tumor	Disease	D009369
2054792	329	339	toxicities	Disease	D064420
2054792	347	357	leukopenia	Disease	D007970
2054792	362	378	thrombocytopenia	Disease	D013921
2054792	403	413	toxicities	Disease	D064420
2054792	421	449	myocardial and kidney injury	Disease	-1
2054792	421	438	myocardial injury	Disease	D006331
2054792	436	449	kidney injury	Disease	D007674
2054792	443	460	myocardial injury	Disease	D006331
2054792	545	557	hyperthermia	Disease	D005334
2054792	600	610	Adriamycin	Chemical	D004317
2054792	883	908	cardiac and renal lesions	Disease	-1
2054792	883	898	cardiac lesions	Disease	D006331
2054792	895	908	renal lesions	Disease	D007674
2054792	901	916	cardiac lesions	Disease	D006331
2054792	961	973	hyperthermia	Disease	D005334
2054792	983	993	Adriamycin	Chemical	D004317
2054792	1035	1043	toxicity	Disease	D064420
2054792	Association	D004317	D005334
2054792	treated	D004317	D009369
2054792	induced	D004317	-1
2054792	induced	D004317	D064420
2054792	induced	D004317	D007970
2054792	induced	D004317	D013921
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|t|Swallowing-induced atrial tachyarrhythmia triggered by salbutamol: case report and review of the literature.
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	treated	D001262	D013617
20552622	induced	D000420	D013617
20552622	treated	D001262	D001145
20552622	treated	D001262	D013610
20552622	induced	D000420	D013610
20552622	induced	D000420	D001145
20588063|a|BACKGROUND/AIMS: It is still unclear what happens in the glomerulus when proteinuria starts. Using puromycin aminonucleoside nephrosis (PAN) rats, we studied early ultrastructural and permeability changes in relation to the expression of the podocyte-associated molecules nephrin, a-actinin, dendrin, and plekhh2, the last two of which were only recently discovered in podocytes. METHODS: Using immune stainings, semiquantitative measurement was performed under the electron microscope. Permeability was assessed using isolated kidney perfusion with tracers. Possible effects of ACE inhibition were tested. RESULTS: By day 2, some patchy foot process effacement, but no proteinuria, appeared. The amount of nephrin was reduced in both diseased and normal areas. The other proteins showed few changes, which were limited to diseased areas. By day 4, foot process effacement was complete and proteinuria appeared in parallel with signs of size barrier damage. Nephrin decreased further, while dendrin and plekhh2 also decreased but a-actinin remained unchanged. ACE inhibition had no significant protective effect. CONCLUSIONS: PAN glomeruli already showed significant pathology by day 4, despite relatively mild proteinuria. This was preceded by altered nephrin expression, supporting its pivotal role in podocyte morphology. The novel proteins dendrin and plekhh2 were both reduced, suggesting roles in PAN, whereas a-actinin was unchanged.
20588063|t|Permeability, ultrastructural changes, and distribution of novel proteins in the glomerular barrier in early puromycin aminonucleoside nephrosis.
20588063	109	134	puromycin aminonucleoside	Chemical	D011692
20588063	135	144	nephrosis	Disease	D009401
20588063	219	230	proteinuria	Disease	D011507
20588063	245	270	puromycin aminonucleoside	Chemical	D011692
20588063	271	280	nephrosis	Disease	D009401
20588063	816	827	proteinuria	Disease	D011507
20588063	1036	1047	proteinuria	Disease	D011507
20588063	1357	1368	proteinuria	Disease	D011507
20588063	induced	D011692	D009401
20588063	induced	D011692	D011507
20633755|a|Suxamethonium causes prolonged apnea in patients in whom pseudocholinesterase enzyme gets deactivated by organophosphorus (OP) poisons. Here, we present a similar incident in a severely depressed patient who received electroconvulsive therapy (ECT). Prolonged apnea in our case ensued because the information about suicidal attempt by OP compound was concealed from the treating team.
20633755|t|Suxamethonium induced prolonged apnea in a patient receiving electroconvulsive therapy.
20633755	0	13	Suxamethonium	Chemical	D013390
20633755	32	37	apnea	Disease	D001049
20633755	88	101	Suxamethonium	Chemical	D013390
20633755	119	124	apnea	Disease	D001049
20633755	193	222	organophosphorus (OP) poisons	Chemical	D009943
20633755	274	283	depressed	Disease	D003866
20633755	348	353	apnea	Disease	D001049
20633755	423	434	OP compound	Chemical	D009943
20633755	induced	D013390	D001049
20633755	induced	D009943	D001049
20882060|a|OBJECTIVE: The globus pallidus plays a critical role in movement regulation. Previous studies have indicated that the globus pallidus receives neurotensinergic innervation from the striatum, and systemic administration of a neurotensin analog could produce antiparkinsonian effects. The present study aimed to investigate the effects of pallidal neurotensin on haloperidol-induced parkinsonian symptoms. METHODS: Behavioral experiments and electrophysiological recordings were performed in the present study. RESULTS: Bilateral infusions of neurotensin into the globus pallidus reversed haloperidol-induced parkinsonian catalepsy in rats. Electrophysiological recordings showed that microinjection of neurotensin induced excitation of pallidal neurons in the presence of systemic haloperidol administration. The neurotensin type-1 receptor antagonist SR48692 blocked both the behavioral and the electrophysiological effects induced by neurotensin. CONCLUSION: Activation of pallidal neurotensin receptors may be involved in neurotensin-induced antiparkinsonian effects.
20882060|t|Effects of pallidal neurotensin on haloperidol-induced parkinsonian catalepsy: behavioral and electrophysiological studies.
20882060	20	31	neurotensin	Chemical	D009496
20882060	35	46	haloperidol	Chemical	D006220
20882060	55	77	parkinsonian catalepsy	Disease	D002375
20882060	348	359	neurotensin	Chemical	D009496
20882060	470	481	neurotensin	Chemical	D009496
20882060	485	496	haloperidol	Chemical	D006220
20882060	505	526	parkinsonian symptoms	Disease	D010302
20882060	665	676	neurotensin	Chemical	D009496
20882060	711	722	haloperidol	Chemical	D006220
20882060	731	753	parkinsonian catalepsy	Disease	D002375
20882060	825	836	neurotensin	Chemical	D009496
20882060	904	915	haloperidol	Chemical	D006220
20882060	936	974	neurotensin type-1 receptor antagonist	Chemical	C079087
20882060	975	982	SR48692	Chemical	C079087
20882060	1059	1070	neurotensin	Chemical	D009496
20882060	1107	1118	neurotensin	Chemical	D009496
20882060	1148	1159	neurotensin	Chemical	D009496
20882060	treated	D009496	D002375
20882060	induced	D006220	D002375
20882060	treated	D009496	D010302
20882060	induced	D006220	D010302
21029050|a|BACKGROUND: patients undergoing electroconvulsive therapy (ECT) often receive succinylcholine as part of the anesthetic procedure. The duration of action may be prolonged in patients with genetic variants of the butyrylcholinesterase enzyme (BChE), the most common being the K- and the A-variants. The aim of the study was to assess the clinical significance of genetic variants in butyrylcholinesterase gene (BCHE) in patients with a suspected prolonged duration of action of succinylcholine after ECT. METHODS: a total of 13 patients were referred to the Danish Cholinesterase Research Unit after ECT during 38 months. We determined the BChE activity and the BCHE genotype using molecular genetic methods, the duration of apnea, time to sufficient spontaneous ventilation and whether neuromuscular monitoring was used. The duration of apnea was compared with published data on normal subjects. RESULTS: in 11 patients, mutations were found in the BCHE gene, the K-variant being the most frequent. The duration of apnea was 5-15 min compared with 3-5.3 min from the literature. Severe distress was noted in the recovery phase in two patients. Neuromuscular monitoring was used in two patients. CONCLUSION: eleven of 13 patients with a prolonged duration of action of succinylcholine had mutations in BCHE, indicating that this is the possible reason for a prolonged period of apnea. We recommend objective neuromuscular monitoring during the first ECT.
21029050|t|Butyrylcholinesterase gene mutations in patients with prolonged apnea after succinylcholine for electroconvulsive therapy.
21029050	64	69	apnea	Disease	D001049
21029050	76	91	succinylcholine	Chemical	D013390
21029050	201	216	succinylcholine	Chemical	D013390
21029050	600	615	succinylcholine	Chemical	D013390
21029050	847	852	apnea	Disease	D001049
21029050	960	965	apnea	Disease	D001049
21029050	1138	1143	apnea	Disease	D001049
21029050	1391	1406	succinylcholine	Chemical	D013390
21029050	1500	1505	apnea	Disease	D001049
21029050	induced	D013390	D001049
2234245|a|During an 18-month period of study 41 hemodialyzed patients receiving desferrioxamine (10-40 mg/kg BW/3 times weekly) for the first time were monitored for detection of audiovisual toxicity. 6 patients presented clinical symptoms of visual or auditory toxicity. Moreover, detailed ophthalmologic and audiologic studies disclosed abnormalities in 7 more asymptomatic patients. Visual toxicity was of retinal origin and was characterized by a tritan-type dyschromatopsy, sometimes associated with a loss of visual acuity and pigmentary retinal deposits. Auditory toxicity was characterized by a mid- to high-frequency neurosensorial hearing loss and the lesion was of the cochlear type. Desferrioxamine withdrawal resulted in a complete recovery of visual function in 1 patient and partial recovery in 3, and a complete reversal of hearing loss in 3 patients and partial recovery in 3. This toxicity appeared in patients receiving the higher doses of desferrioxamine or coincided with the normalization of ferritin or aluminium serum levels. The data indicate that audiovisual toxicity is not an infrequent complication in hemodialyzed patients receiving desferrioxamine. Periodical audiovisual monitoring should be performed on hemodialyzed patients receiving the drug in order to detect adverse effects as early as possible.
2234245|t|Ocular and auditory toxicity in hemodialyzed patients receiving desferrioxamine.
2234245	11	28	auditory toxicity	Disease	D006311
2234245	64	79	desferrioxamine	Chemical	D003676
2234245	151	166	desferrioxamine	Chemical	D003676
2234245	250	270	audiovisual toxicity	Disease	D006311
2234245	324	341	auditory toxicity	Disease	D006311
2234245	457	472	Visual toxicity	Disease	D014786
2234245	534	548	dyschromatopsy	Disease	-1
2234245	576	599	a loss of visual acuity	Disease	D014786
2234245	604	631	pigmentary retinal deposits	Disease	D012164
2234245	633	650	Auditory toxicity	Disease	D006311
2234245	697	724	neurosensorial hearing loss	Disease	D006319
2234245	766	781	Desferrioxamine	Chemical	D003676
2234245	911	923	hearing loss	Disease	D034381
2234245	970	978	toxicity	Disease	D064420
2234245	1030	1045	desferrioxamine	Chemical	D003676
2234245	1097	1106	aluminium	Chemical	-1
2234245	1144	1164	audiovisual toxicity	Disease	D006311
2234245	1234	1249	desferrioxamine	Chemical	D003676
2234245	induced	D003676	D006311
2234245	induced	D003676	-1
2234245	induced	D003676	D012164
2234245	induced	D003676	D006319
2234245	induced	D003676	D034381
2234245	induced	D003676	D064420
2234245	induced	D003676	D014786
2266990|a|There is evidence that growth hormone may be related to the progression of weakness in Duchenne dystrophy. We conducted a 12-month controlled trial of mazindol, a putative growth hormone secretion inhibitor, in 83 boys with Duchenne dystrophy. Muscle strength, contractures, functional ability and pulmonary function were tested at baseline, and 6 and 12 months after treatment with mazindol (3 mg/d) or placebo. The study was designed to have a power of greater than 0.90 to detect a slowing to 25% of the expected rate of progression of weakness at P less than 0.05. Mazindol did not benefit strength at any point in the study. Side effects attributable to mazindol included decreased appetite (36%), dry mouth (10%), behavioral change (22%), and gastrointestinal symptoms (18%); mazindol dosage was reduced in 43% of patients. The effect of mazindol on GH secretion was estimated indirectly by comparing the postabsorptive IGF-I levels obtained following 3, 6, 9, and 12 months in the mazindol treated to those in the placebo groups. Although mazindol-treated patients gained less weight and height than placebo-treated patients, no significant effect on IGF-I levels was observed. Mazindol doses not slow the progression of weakness in Duchenne dystrophy.
2266990|t|Randomized, double-blind trial of mazindol in Duchenne dystrophy.
2266990	34	42	mazindol	Chemical	D008454
2266990	46	64	Duchenne dystrophy	Disease	D020388
2266990	141	149	weakness	Disease	D018908
2266990	153	171	Duchenne dystrophy	Disease	D020388
2266990	217	225	mazindol	Chemical	D008454
2266990	290	308	Duchenne dystrophy	Disease	D020388
2266990	449	457	mazindol	Chemical	D008454
2266990	605	613	weakness	Disease	D018908
2266990	635	643	Mazindol	Chemical	D008454
2266990	725	733	mazindol	Chemical	D008454
2266990	743	761	decreased appetite	Disease	D001068
2266990	769	778	dry mouth	Disease	D014987
2266990	815	840	gastrointestinal symptoms	Disease	D012817
2266990	848	856	mazindol	Chemical	D008454
2266990	910	918	mazindol	Chemical	D008454
2266990	1054	1062	mazindol	Chemical	D008454
2266990	1112	1120	mazindol	Chemical	D008454
2266990	1251	1259	Mazindol	Chemical	D008454
2266990	1294	1302	weakness	Disease	D018908
2266990	1306	1324	Duchenne dystrophy	Disease	D020388
2266990	induced	D008454	D001068
2266990	induced	D008454	D014987
2266990	induced	D008454	D012817
2515254|a|Twenty common migraine patients received a one sided frontotemporal application of nitroglycerin (10 patients) or placebo ointment (10 patients) in a double blind study. Early onset migraine attacks were induced by nitroglycerin in seven out of 10 patients versus no patient in the placebo group. Subsequently 20 migraine patients, who developed an early onset attack with frontotemporal nitroglycerin, received the drug in a second induction test at other body areas. No early onset migraine was observed. Thus the migraine-inducing effect of nitroglycerin seems to depend on direct stimulation of the habitual site of pain, suggesting that the frontotemporal region is of crucial importance in the development of a migraine crisis. This is not consistent with a CNS origin of migraine attack.
2515254|t|Source of pain and primitive dysfunction in migraine: an identical site?
2515254	10	14	pain	Disease	D010146
2515254	44	52	migraine	Disease	D008881
2515254	87	95	migraine	Disease	D008881
2515254	156	169	nitroglycerin	Chemical	D005996
2515254	255	263	migraine	Disease	D008881
2515254	288	301	nitroglycerin	Chemical	D005996
2515254	386	394	migraine	Disease	D008881
2515254	461	474	nitroglycerin	Chemical	D005996
2515254	557	565	migraine	Disease	D008881
2515254	589	597	migraine	Disease	D008881
2515254	617	630	nitroglycerin	Chemical	D005996
2515254	693	697	pain	Disease	D010146
2515254	790	798	migraine	Disease	D008881
2515254	851	859	migraine	Disease	D008881
2515254	induced	D005996	D010146
2515254	induced	D005996	D008881
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|t|National project on the prevention of mother-to-infant infection by hepatitis B virus in Japan.
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	induced	D006514	D006509
2533791	induced	D006513	D006509
2533791	induced	D017325	D006509
2559236|a|The effect of the converting enzyme inhibitor (CEI) enalapril was assessed in Munich-Wistar rats with established adriamycin nephrosis. Rats were given a single dose of adriamycin and one month later divided into four groups matched for albuminuria, blood pressure, and plasma albumin concentration. Groups 1 and 3 remained untreated while groups 2 and 4 received enalapril. Groups 1 and 2 underwent micropuncture studies after 10 days. These short-term studies showed that enalapril reduced arterial blood pressure (101 +/- 2 vs. 124 +/- 3 mm Hg, group 2 vs. 1, P less than 0.05) and glomerular capillary pressure (54 +/- 1 vs. 61 +/- 2 mm Hg, P less than 0.05) without reducing albuminuria (617 +/- 50 vs. 570 +/- 47 mg/day) or GFR (1.03 +/- 0.04 vs. 1.04 +/- 0.11 ml/min). Groups 3 and 4 were studied at four and at six months to assess the effect of enalapril on progression of renal injury in adriamycin nephrosis. Chronic enalapril treatment reduced blood pressure without reducing albuminuria in group 4. Untreated group 3 rats exhibited a progressive reduction in GFR (0.35 +/- 0.08 ml/min at 4 months, 0.27 +/- 0.07 ml/min at 6 months). Enalapril treatment blunted but did not prevent reduction in GFR in group 4 (0.86 +/- 0.15 ml/min at 4 months, 0.69 +/- 0.13 ml/min at 6 months, both P less than 0.05 vs. group 3). Reduction in GFR was associated with the development of glomerular sclerosis in both treated and untreated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
2559236|t|Effect of converting enzyme inhibition on the course of adriamycin-induced nephropathy.
2559236	56	66	adriamycin	Chemical	D004317
2559236	75	86	nephropathy	Disease	D007674
2559236	140	149	enalapril	Chemical	D004656
2559236	202	212	adriamycin	Chemical	D004317
2559236	213	222	nephrosis	Disease	D009401
2559236	257	267	adriamycin	Chemical	D004317
2559236	325	336	albuminuria	Disease	D000419
2559236	452	461	enalapril	Chemical	D004656
2559236	562	571	enalapril	Chemical	D004656
2559236	768	779	albuminuria	Disease	D000419
2559236	942	951	enalapril	Chemical	D004656
2559236	970	982	renal injury	Disease	D007674
2559236	986	996	adriamycin	Chemical	D004317
2559236	997	1006	nephrosis	Disease	D009401
2559236	1016	1025	enalapril	Chemical	D004656
2559236	1076	1087	albuminuria	Disease	D000419
2559236	1234	1243	Enalapril	Chemical	D004656
2559236	1471	1491	glomerular sclerosis	Disease	D007674
2559236	induced	D004317	D007674
2559236	treated	D004656	D007674
2559236	treated	D004656	D009401
2559236	induced	D004317	D009401
2559236	induced	D004317	D000419
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|t|Involvement of locus coeruleus and noradrenergic neurotransmission in fentanyl-induced muscular rigidity in the rat.
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	induced	D005283	D009127
2564649	treated	D011224	D009127
2611118|a|Diclofenac sodium (Voltarol, Geigy Pharmaceuticals) is a non-steroidal anti-inflammatory derivative of phenylacetic acid. Although generally well-tolerated, asymptomatic abnormalities of liver function have been recorded and, less commonly, severe hepatitis induced by diclofenac. The patient described developed chronic active hepatitis after six months therapy with diclofenac sodium which progressed despite the withdrawal of the drug, a finding not previously reported.
2611118|t|Chronic active hepatitis associated with diclofenac sodium therapy.
2611118	0	24	Chronic active hepatitis	Disease	D006521
2611118	41	58	diclofenac sodium	Chemical	D004008
2611118	68	85	Diclofenac sodium	Chemical	D004008
2611118	87	95	Voltarol	Chemical	D004008
2611118	171	188	phenylacetic acid	Chemical	C025136
2611118	238	269	abnormalities of liver function	Disease	D056486
2611118	316	325	hepatitis	Disease	D056486
2611118	337	347	diclofenac	Chemical	D004008
2611118	381	405	chronic active hepatitis	Disease	D006521
2611118	436	453	diclofenac sodium	Chemical	D004008
2611118	induced	D004008	D056486
2611118	induced	D004008	D006521
2632720|a|Two of 14 patients with Cushing's syndrome treated on a long-term basis with ketoconazole developed sustained hypertension. In both cases normal plasma and urinary free cortisol levels had been achieved following ketoconazole therapy, yet continuous blood pressure monitoring demonstrated hypertension 31 (patient 1) and 52 weeks (patient 2) after treatment. In patient 1, plasma levels of deoxycorticosterone and 11-deoxycortisol were elevated. In patient 2, in addition to an increase in both deoxycorticosterone and 11-deoxycortisol levels, plasma aldosterone values were raised, with a concomitant suppression of renin levels. Our findings show that long-term treatment with high doses of ketoconazole may induce enzyme blockade leading to mineralocorticoid-related hypertension.
2632720|t|Arterial hypertension as a complication of prolonged ketoconazole treatment.
2632720	9	21	hypertension	Disease	D006973
2632720	53	65	ketoconazole	Chemical	D007654
2632720	101	119	Cushing's syndrome	Disease	D003480
2632720	154	166	ketoconazole	Chemical	D007654
2632720	187	199	hypertension	Disease	D006973
2632720	246	254	cortisol	Chemical	D006854
2632720	290	302	ketoconazole	Chemical	D007654
2632720	366	378	hypertension	Disease	D006973
2632720	467	486	deoxycorticosterone	Chemical	D003900
2632720	491	507	11-deoxycortisol	Chemical	D003350
2632720	572	591	deoxycorticosterone	Chemical	D003900
2632720	596	612	11-deoxycortisol	Chemical	D003350
2632720	628	639	aldosterone	Chemical	D000450
2632720	770	782	ketoconazole	Chemical	D007654
2632720	847	859	hypertension	Disease	D006973
2632720	induced	D007654	D006973
2632720	induced	D000450	D006973
2632720	treated	D007654	D003480
2632720	induced	D006854	D003480
2632720	induced	D003900	D006973
2632720	induced	D003350	D006973
2673163|a|We describe eight patients in whom cocaine use was related to stroke and review 39 cases from the literature. Among these 47 patients the mean (+/- SD) age was 32.5 +/- 12.1 years; 76% (34/45) were men. Stroke followed cocaine use by inhalation, intranasal, intravenous, and intramuscular routes. Intracranial aneurysms or arteriovenous malformations were present in 17 of 32 patients studied angiographically or at autopsy; cerebral vasculitis was present in two patients. Cerebral infarction occurred in 10 patients (22%), intracerebral hemorrhage in 22 (49%), and subarachnoid hemorrhage in 13 (29%). These data indicate that (1) the apparent incidence of stroke related to cocaine use is increasing; (2) cocaine-associated stroke occurs primarily in young adults; (3) stroke may follow any route of cocaine administration; (4) stroke after cocaine use is frequently associated with intracranial aneurysms and arteriovenous malformations; and (5) in cocaine-associated stroke, the frequency of intracranial hemorrhage exceeds that of cerebral infarction.
2673163|t|Stroke associated with cocaine use.
2673163	0	6	Stroke	Disease	D020521
2673163	23	30	cocaine	Chemical	D003042
2673163	71	78	cocaine	Chemical	D003042
2673163	98	104	stroke	Disease	D020521
2673163	239	245	Stroke	Disease	D020521
2673163	255	262	cocaine	Chemical	D003042
2673163	333	355	Intracranial aneurysms	Disease	D002532
2673163	359	386	arteriovenous malformations	Disease	D001165
2673163	461	480	cerebral vasculitis	Disease	D020293
2673163	510	529	Cerebral infarction	Disease	D002544
2673163	561	585	intracerebral hemorrhage	Disease	D002543
2673163	603	626	subarachnoid hemorrhage	Disease	D013345
2673163	695	701	stroke	Disease	D020521
2673163	713	720	cocaine	Chemical	D003042
2673163	744	751	cocaine	Chemical	D003042
2673163	763	769	stroke	Disease	D020521
2673163	808	814	stroke	Disease	D020521
2673163	839	846	cocaine	Chemical	D003042
2673163	867	873	stroke	Disease	D020521
2673163	880	887	cocaine	Chemical	D003042
2673163	922	944	intracranial aneurysms	Disease	D002532
2673163	949	976	arteriovenous malformations	Disease	D001165
2673163	989	996	cocaine	Chemical	D003042
2673163	1008	1014	stroke	Disease	D020521
2673163	1033	1056	intracranial hemorrhage	Disease	D020300
2673163	1073	1092	cerebral infarction	Disease	D002544
2673163	induced	D003042	D002543
2673163	induced	D003042	D013345
2673163	induced	D003042	D020521
2673163	induced	D003042	D020300
2673163	Association	D003042	D002532
2673163	Association	D003042	D001165
2673163	Association	D003042	D020293
2673163	induced	D003042	D002544
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|t|Beta-2-adrenoceptor-mediated hypokalemia and its abolishment by oxprenolol.
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	treated	D011188	D007008
2826064	treated	D010096	D007008
2826064	induced	D013726	D007008
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|t|Glycopyrronium requirements for antagonism of the muscarinic side effects of edrophonium.
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	treated	D006024	D001919
2917114	induced	D004491	D001919
2950248|a|Angina and ischemic electrocardiographic changes occurred after administration of oral dipyridamole in four patients awaiting urgent myocardial revascularization procedures. To our knowledge, this has not previously been reported as a side effect of preoperative dipyridamole therapy, although dipyridamole-induced myocardial ischemia has been demonstrated to occur in animals and humans with coronary artery disease. Epicardial coronary collateral vessels were demonstrated in all four patients; a coronary "steal" phenomenon may be the mechanism of the dipyridamole-induced ischemia observed.
2950248|t|Dipyridamole-induced myocardial ischemia.
2950248	0	12	Dipyridamole	Chemical	D004176
2950248	21	40	myocardial ischemia	Disease	D017202
2950248	42	48	Angina	Disease	D000787
2950248	129	141	dipyridamole	Chemical	D004176
2950248	305	317	dipyridamole	Chemical	D004176
2950248	336	348	dipyridamole	Chemical	D004176
2950248	357	376	myocardial ischemia	Disease	D017202
2950248	435	458	coronary artery disease	Disease	D003324
2950248	597	609	dipyridamole	Chemical	D004176
2950248	618	626	ischemia	Disease	D007511
2950248	induced	D004176	D000787
2950248	induced	D004176	D017202
2950248	Association	D004176	D003324
2950248	induced	D004176	D007511
3070035|a|We report a case of severe hypertension with an occluded renal artery to a solitary kidney, who developed sudden deterioration of renal function following treatment with captopril. His renal function remained impaired but stable during 2 years' treatment with captopril but returned to pre-treatment levels soon after cessation of the drug. This indicates reversibility in captopril-induced renal failure even after its prolonged use and suggests that no organic damage occurs to glomerular arterioles following chronic ACE inhibition.
3070035|t|Reversibility of captopril-induced renal insufficiency after prolonged use in an unusual case of renovascular hypertension.
3070035	17	26	captopril	Chemical	D002216
3070035	35	54	renal insufficiency	Disease	D051437
3070035	97	122	renovascular hypertension	Disease	D006978
3070035	151	163	hypertension	Disease	D006973
3070035	230	268	sudden deterioration of renal function	Disease	D058186
3070035	294	303	captopril	Chemical	D002216
3070035	384	393	captopril	Chemical	D002216
3070035	497	506	captopril	Chemical	D002216
3070035	515	528	renal failure	Disease	D051437
3070035	treated	D002216	D006973
3070035	induced	D002216	D058186
3070035	induced	D002216	D051437
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|t|Chorea associated with oral contraception.
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	induced	D000661	D002819
3123611	induced	D003276	D002819
3125768|a|Intracranial pressure (ICP) was measured during alfentanil-induced rigidity in rats. Ten rats had arterial, central venous (CVP), and subdural cannulae inserted under halothane anesthesia. The animals were mechanically ventilated to achieve normocarbia (PCO2 = 42 +/- 1 mmHg, mean +/- SE). Following instrumentation, halothane was discontinued and alfentanil (125 mu/kg) administered iv during emergence from halothane anesthesia. In the five rats that developed somatic rigidity, ICP and CVP increased significantly above baseline (delta ICP 7.5 +/- 1.0 mmHg, delta CVP 5.9 +/- 1.3 mmHg). These variables returned to baseline when rigidity was abolished with metocurine. In five rats that did not become rigid, ICP and CVP did not change following alfentanil. These observations suggest that rigidity should be prevented when alfentanil, and, presumably, other opiates, are used in the anesthetic management of patients with ICP problems.
3125768|t|Intracranial pressure increases during alfentanil-induced rigidity.
3125768	39	49	alfentanil	Chemical	D015760
3125768	58	66	rigidity	Disease	D009127
3125768	116	126	alfentanil	Chemical	D015760
3125768	135	143	rigidity	Disease	D009127
3125768	235	244	halothane	Chemical	D006221
3125768	385	394	halothane	Chemical	D006221
3125768	416	426	alfentanil	Chemical	D015760
3125768	477	486	halothane	Chemical	D006221
3125768	531	547	somatic rigidity	Disease	D009127
3125768	700	708	rigidity	Disease	D009127
3125768	728	738	metocurine	Chemical	C032943
3125768	817	827	alfentanil	Chemical	D015760
3125768	861	869	rigidity	Disease	D009127
3125768	895	905	alfentanil	Chemical	D015760
3125768	treated	C032943	D009127
3125768	induced	D015760	D009127
3187073|a|Survival for patients with advanced head and neck carcinoma and esophageal carcinoma is poor with radiotherapy and/or surgery. Obviously, there is a need for effective chemotherapy. In the present study, cis-platin (80-120 mg/m2BSA) and 5-FU (1000 mg/m2BSA daily as a continuous infusion during 5 days) were given to 76 patients before radiotherapy and surgery. The aim of the study was to clarify the incidence and severity of adverse cardiac effects to this treatment. Before treatment all patients had a cardiac evaluation and during treatment serial ECG recordings were performed. In the pre-treatment evaluation, signs of cardiovascular disease were found in 33 patients (43%). During treatment, adverse cardiac effects were observed in 14 patients (18%). The mean age of these patients was the same as for the entire group, 64 years. The incidence of cardiotoxicity was not higher in patients with signs of cardiovascular disease than in those without in the pre-treatment evaluation. The most common signs of cardiotoxicity were chest pain, ST-T wave changes and atrial fibrillation. This was followed by ventricular fibrillation in one patient and sudden death in another. It is concluded that patients on 5-FU treatment should be under close supervision and that the treatment should be discontinued if chest pain or tachyarrhythmia is observed.
3187073|t|Adverse cardiac effects during induction chemotherapy treatment with cis-platin and 5-fluorouracil.
3187073	69	79	cis-platin	Chemical	D002945
3187073	84	98	5-fluorouracil	Chemical	D005472
3187073	136	159	head and neck carcinoma	Disease	D006258
3187073	164	184	esophageal carcinoma	Disease	D004938
3187073	304	314	cis-platin	Chemical	D002945
3187073	337	341	5-FU	Chemical	D005472
3187073	727	749	cardiovascular disease	Disease	D002318
3187073	957	971	cardiotoxicity	Disease	D066126
3187073	1013	1035	cardiovascular disease	Disease	D002318
3187073	1116	1130	cardiotoxicity	Disease	D066126
3187073	1136	1146	chest pain	Disease	D002637
3187073	1170	1189	atrial fibrillation	Disease	D001281
3187073	1212	1236	ventricular fibrillation	Disease	D014693
3187073	1256	1268	sudden death	Disease	D003645
3187073	1314	1318	5-FU	Chemical	D005472
3187073	1412	1422	chest pain	Disease	D002637
3187073	1426	1441	tachyarrhythmia	Disease	D013610
3187073	induced	D005472	D002637
3187073	induced	D005472	D001281
3187073	induced	D005472	D014693
3187073	induced	D005472	D003645
3187073	induced	D005472	D066126
3187073	treated	D002945	D006258
3187073	treated	D005472	D006258
3187073	treated	D002945	D004938
3187073	treated	D005472	D004938
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|t|Receptor mechanisms of nicotine-induced locomotor hyperactivity in chronic nicotine-treated rats.
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	induced	D009538	D006948
3220106	induced	D004298	D006948
3341566|a|The systolic pressure variation (SPV), which is the difference between the maximal and minimal values of the systolic blood pressure (SBP) after one positive-pressure breath, was studied in ventilated dogs subjected to hypotension. Mean arterial pressure was decreased to 50 mm Hg for 30 minutes either by hemorrhage (HEM, n = 7) or by continuous infusion of sodium nitroprusside (SNP, n = 7). During HEM-induced hypotension the cardiac output was significantly lower and systemic vascular resistance higher compared with that in the SNP group. The systemic, central venous, pulmonary capillary wedge pressures, and heart rates, were similar in the two groups. Analysis of the respiratory changes in the arterial pressure waveform enabled differentiation between the two groups. The SPV during hypotension was 15.7 +/- 6.7 mm Hg in the HEM group, compared with 9.1 +/- 2.0 mm Hg in the SNP group (P less than 0.02). The delta down, which is the measure of decrease of SBP after a mechanical breath, was 20.3 +/- 8.4 and 10.1 +/- 3.8 mm Hg in the HEM and SNP groups, respectively, during hypotension (P less than 0.02). It is concluded that increases in the SPV and the delta down are characteristic of a hypotensive state due to a predominant decrease in preload. They are thus more important during absolute hypovolemia than during deliberate hypotension.
3341566|t|Systolic pressure variation is greater during hemorrhage than during sodium nitroprusside-induced hypotension in ventilated dogs.
3341566	46	56	hemorrhage	Disease	D006470
3341566	69	89	sodium nitroprusside	Chemical	D009599
3341566	98	109	hypotension	Disease	D007022
3341566	349	360	hypotension	Disease	D007022
3341566	436	446	hemorrhage	Disease	D006470
3341566	448	451	HEM	Disease	D006470
3341566	489	509	sodium nitroprusside	Chemical	D009599
3341566	511	514	SNP	Chemical	D009599
3341566	531	534	HEM	Disease	D006470
3341566	543	554	hypotension	Disease	D007022
3341566	664	667	SNP	Chemical	D009599
3341566	924	935	hypotension	Disease	D007022
3341566	966	969	HEM	Disease	D006470
3341566	1016	1019	SNP	Chemical	D009599
3341566	1176	1179	HEM	Disease	D006470
3341566	1184	1187	SNP	Chemical	D009599
3341566	1217	1228	hypotension	Disease	D007022
3341566	1334	1345	hypotensive	Disease	D007022
3341566	1439	1450	hypovolemia	Disease	D020896
3341566	1474	1485	hypotension	Disease	D007022
3341566	induced	D009599	D007022
3371379|a|Two patients with signs of carbamazepine neurotoxicity after combined treatment with verapamil showed complete recovery after discontinuation of the calcium entry blocker. Use of verapamil in combination with carbamazepine should either be avoided or prescribed only with appropriate adjustment of the carbamazepine dose (usually reduction of the carbamazepine dose by one half).
3371379|t|Verapamil-induced carbamazepine neurotoxicity. A report of two cases.
3371379	0	9	Verapamil	Chemical	D014700
3371379	18	31	carbamazepine	Chemical	D002220
3371379	32	45	neurotoxicity	Disease	D020258
3371379	97	110	carbamazepine	Chemical	D002220
3371379	111	124	neurotoxicity	Disease	D020258
3371379	155	164	verapamil	Chemical	D014700
3371379	219	226	calcium	Chemical	D002118
3371379	249	258	verapamil	Chemical	D014700
3371379	279	292	carbamazepine	Chemical	D002220
3371379	372	385	carbamazepine	Chemical	D002220
3371379	417	430	carbamazepine	Chemical	D002220
3371379	induced	D014700	D020258
3371379	induced	D002220	D020258
3409645|a|The relationship of arthritis and sexual dysfunction was investigated among 169 patients with rheumatoid arthritis, osteoarthritis and spondyloarthropathy, 130 of whom were pair-matched to controls. Assessments of marital happiness and depressed mood were also made using the CES-D and the Azrin Marital Happiness Scale (AMHS). Sexual dysfunctions were found to be common among patients and controls, the majority in both groups reporting one or more dysfunctions. Impotence was more common among male patients than controls and was found to be associated with co-morbidity and the taking of methotrexate. Depressed mood was more common among patients and was associated with certain sexual difficulties, but not with impotence. Marital unhappiness, as indicated by AMHS scores, was not associated with arthritis but was associated with sexual dysfunction, sexual dissatisfaction and being female.
3409645|t|Sexual dysfunction among patients with arthritis.
3409645	0	18	Sexual dysfunction	Disease	D012735
3409645	39	48	arthritis	Disease	D001168
3409645	70	79	arthritis	Disease	D001168
3409645	84	102	sexual dysfunction	Disease	D012735
3409645	144	164	rheumatoid arthritis	Disease	D001172
3409645	166	180	osteoarthritis	Disease	D010003
3409645	185	204	spondyloarthropathy	Disease	D025242
3409645	286	300	depressed mood	Disease	D003866
3409645	378	397	Sexual dysfunctions	Disease	D012735
3409645	515	524	Impotence	Disease	D007172
3409645	642	654	methotrexate	Chemical	D008727
3409645	656	670	Depressed mood	Disease	D003866
3409645	768	777	impotence	Disease	D007172
3409645	853	862	arthritis	Disease	D001168
3409645	887	905	sexual dysfunction	Disease	D012735
3409645	treated	D008727	D001172
3409645	treated	D008727	D025242
3409645	induced	D008727	D007172
3503576|a|Visual and auditory neurotoxicity was previously documented in 42 of 89 patients with transfusion-dependent anemia who were receiving iron chelation therapy with daily subcutaneous deferoxamine. Twenty-two patients in the affected group had abnormal audiograms with deficits mostly in the high frequency range of 4,000 to 8,000 Hz and in the hearing threshold levels of 30 to 100 decibels. When deferoxamine therapy was discontinued and serial studies were performed, audiograms in seven cases reverted to normal or near normal within two to three weeks, and nine of 13 patients with symptoms became asymptomatic. Audiograms from 15 patients remained abnormal and four patients required hearing aids because of permanent disability. Since 18 of the 22 patients were initially receiving deferoxamine doses in excess of the commonly recommended 50 mg/kg per dose, therapy was restarted with lower doses, usually 50 mg/kg per dose or less depending on the degree of auditory abnormality, and with the exception of two cases no further toxicity was demonstrated. Auditory deterioration and improvement, demonstrated serially in individual patients receiving and not receiving deferoxamine, respectively, provided convincing evidence for a cause-and-effect relation between deferoxamine administration and ototoxicity. Based on these data, a plan of management was developed that allows effective yet safe administration of deferoxamine. A dose of 50 mg/kg is recommended in those without audiogram abnormalities. With mild toxicity, a reduction to 30 or 40 mg/kg per dose should result in a reversal of the abnormal results to normal within four weeks. Moderate abnormalities require a reduction of deferoxamine to 25 mg/kg per dose with careful monitoring. In those with symptoms of hearing loss, the drug should be stopped for four weeks, and when the audiogram is stable or improved, therapy should be restarted at 10 to 25 mg/kg per dose. Serial audiograms should be performed every six months in those without problems and more frequently in young patients with normal serum ferritin values and in those with auditory dysfunction.
3503576|t|Serial studies of auditory neurotoxicity in patients receiving deferoxamine therapy.
3503576	18	40	auditory neurotoxicity	Disease	D006311
3503576	63	75	deferoxamine	Chemical	D003676
3503576	85	118	Visual and auditory neurotoxicity	Disease	D014786|D006311
3503576	85	105	Visual neurotoxicity	Disease	D014786
3503576	96	118	auditory neurotoxicity	Disease	D006311
3503576	105	125	Visual neurotoxicity	Disease	D014786
3503576	193	199	anemia	Disease	D000740
3503576	219	223	iron	Chemical	D007501
3503576	266	278	deferoxamine	Chemical	D003676
3503576	326	415	abnormal audiograms with deficits mostly in the high frequency range of 4,000 to 8,000 Hz	Disease	D006316
3503576	480	492	deferoxamine	Chemical	D003676
3503576	796	816	permanent disability	Disease	D003638
3503576	871	883	deferoxamine	Chemical	D003676
3503576	1048	1068	auditory abnormality	Disease	D006311
3503576	1117	1125	toxicity	Disease	D064420
3503576	1257	1269	deferoxamine	Chemical	D003676
3503576	1354	1366	deferoxamine	Chemical	D003676
3503576	1386	1397	ototoxicity	Disease	D006311
3503576	1504	1516	deferoxamine	Chemical	D003676
3503576	1604	1612	toxicity	Disease	D064420
3503576	1780	1792	deferoxamine	Chemical	D003676
3503576	1865	1877	hearing loss	Disease	D034381
3503576	2195	2215	auditory dysfunction	Disease	D006311
3503576	induced	D003676	D006311
3503576	induced	D003676	D003638
3503576	induced	D003676	D064420
3503576	induced	D003676	D034381
3503576	treated	D007501	D000740
3503576	treated	D003676	D000740
3503576	induced	D003676	D006316
354896|a|Intravenous administration of a single 50-mg bolus of lidocaine in a 67-year-old man resulted in profound depression of the activity of the sinoatrial and atrioventricular nodal pacemakers. The patient had no apparent associated conditions which might have predisposed him to the development of bradyarrhythmias; and, thus, this probably represented a true idiosyncrasy to lidocaine.
354896|t|Lidocaine-induced cardiac asystole.
354896	0	9	Lidocaine	Chemical	D008012
354896	18	34	cardiac asystole	Disease	D006323
354896	90	99	lidocaine	Chemical	D008012
354896	133	224	profound depression of the activity of the sinoatrial and atrioventricular nodal pacemakers	Disease	-1
354896	142	152	depression	Disease	D003866
354896	331	347	bradyarrhythmias	Disease	D001919
354896	409	418	lidocaine	Chemical	D008012
354896	induced	D008012	D006323
354896	induced	D008012	D001919
354896	induced	D008012	-1
3560095|a|Thirty-four patients with juvenile rheumatoid arthritis, who were treated with flurbiprofen at a maximum dose of 4 mg/kg/day, had statistically significant decreases from baseline in 6 arthritis indices after 12 weeks of treatment. Improvements were seen in the number of tender joints, the severity of swelling and tenderness, the time of walk 50 feet, the duration of morning stiffness and the circumference of the left knee. The most frequently observed side effect was fecal occult blood (25% of patients); however, there was no other evidence of gastrointestinal (GI) bleeding in these patients. One patient was prematurely discontinued from the study for severe headache and abdominal pain. Most side effects were mild and related to the GI tract.
3560095|t|Flurbiprofen in the treatment of juvenile rheumatoid arthritis.
3560095	0	12	Flurbiprofen	Chemical	D005480
3560095	33	62	juvenile rheumatoid arthritis	Disease	D001171
3560095	90	119	juvenile rheumatoid arthritis	Disease	D001171
3560095	143	155	flurbiprofen	Chemical	D005480
3560095	249	258	arthritis	Disease	D001168
3560095	336	349	tender joints	Disease	-1
3560095	367	375	swelling	Disease	D004487
3560095	380	390	tenderness	Disease	-1
3560095	434	451	morning stiffness	Disease	-1
3560095	537	555	fecal occult blood	Disease	-1
3560095	615	645	gastrointestinal (GI) bleeding	Disease	D006471
3560095	732	740	headache	Disease	D006261
3560095	745	759	abdominal pain	Disease	D015746
3560095	induced	D005480	D006261
3560095	induced	D005480	D015746
3560095	treated	D005480	D001171
3560095	treated	D005480	D001168
3560095	treated	D005480	-1
3560095	treated	D005480	D004487
3560095	treated	D005480	-1
3560095	induced	D005480	-1
3693336|a|Large doses of triazolam repeatedly induced brief episodes of mania in a depressed elderly woman. Features of organic mental disorder (delirium) were not present. Manic excitement was coincident with the duration of action of triazolam. The possible contribution of the triazolo group to changes in affective status is discussed.
3693336|t|Triazolam-induced brief episodes of secondary mania in a depressed patient.
3693336	0	9	Triazolam	Chemical	D014229
3693336	46	51	mania	Disease	D001714
3693336	57	66	depressed	Disease	D003866
3693336	91	100	triazolam	Chemical	D014229
3693336	138	143	mania	Disease	D001714
3693336	149	158	depressed	Disease	D003866
3693336	186	209	organic mental disorder	Disease	D019965
3693336	211	219	delirium	Disease	D003693
3693336	239	244	Manic	Disease	D001714
3693336	302	311	triazolam	Chemical	D014229
3693336	346	354	triazolo	Chemical	D014229
3693336	induced	D014229	D001714
3693336	treated	D014229	D003866
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|t|Hyperglycemic acidotic coma and death in Kearns-Sayre syndrome.
3703509	0	27	Hyperglycemic acidotic coma	Disease	D006943|D000140|D003128
3703509	0	13	Hyperglycemic	Disease	D006943
3703509	14	22	acidotic	Disease	D000140
3703509	23	27	coma	Disease	D003128
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	induced	D011241	D006963
3703509	induced	D011241	D011141
3703509	induced	D011241	D003128
3703509	induced	D011241	D007022
3703509	induced	D011241	D006943
3703509	induced	D019344	D000138
3703509	induced	D011241	D000138
3703509	induced	D019344	D000140
3703509	induced	D011241	D012131
3703509	induced	D011241	-1
3703509	induced	D011241	D053609
3703509	induced	D011241	D006970
3703509	induced	D011241	D059606
3714122|a|The correlation between neuropathic damage and inhibition of neurotoxic esterase or neuropathy target enzyme (NTE) was examined in rats acutely exposed to Mipafox (N, N'-diisopropylphosphorodiamidofluoridate), a neurotoxic organophosphate. Brain and spinal cord NTE activities were measured in Long-Evans male rats 1 hr post-exposure to various dosages of Mipafox (ip, 1-15 mg/kg). These data were correlated with histologically scored cervical cord damage in a separate group of similarly dosed rats sampled 14-21 days post-exposure. Those dosages (greater than or equal to 10 mg/kg) that inhibited mean NTE activity in the spinal cord greater than or equal to 73% and brain greater than or equal to 67% of control values produced severe (greater than or equal to 3) cervical cord pathology in 85% of the rats. In contrast, dosages of Mipafox (less than or equal to 5 mg/kg) which inhibited mean NTE activity in spinal cord less than or equal to 61% and brain less than or equal to 60% produced this degree of cord damage in only 9% of the animals. These data indicate that a critical percentage of NTE inhibition in brain and spinal cord sampled shortly after Mipafox exposure can predict neuropathic damage in rats several weeks later.
3714122|t|The correlation between neurotoxic esterase inhibition and mipafox-induced neuropathic damage in rats.
3714122	24	34	neurotoxic	Disease	D020258
3714122	59	66	mipafox	Chemical	C005238
3714122	75	93	neuropathic damage	Disease	D009422
3714122	127	145	neuropathic damage	Disease	D009422
3714122	164	174	neurotoxic	Disease	D020258
3714122	187	197	neuropathy	Disease	D009422
3714122	258	265	Mipafox	Chemical	C005238
3714122	267	310	N, N'-diisopropylphosphorodiamidofluoridate	Chemical	C005238
3714122	315	325	neurotoxic	Disease	D020258
3714122	326	341	organophosphate	Chemical	D010755
3714122	459	466	Mipafox	Chemical	C005238
3714122	548	559	cord damage	Disease	D013118
3714122	939	946	Mipafox	Chemical	C005238
3714122	1114	1125	cord damage	Disease	D013118
3714122	1265	1272	Mipafox	Chemical	C005238
3714122	1294	1312	neuropathic damage	Disease	D009422
3714122	induced	C005238	D013118
3714122	induced	D010755	D013118
3714122	induced	C005238	D009422
3714122	induced	D010755	D009422
3714122	induced	C005238	D020258
3714122	induced	D010755	D020258
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|t|Bradycardia due to trihexyphenidyl hydrochloride.
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	induced	D014282	D001919
3827439|a|A patient with cryptogenic cirrhosis and disseminated sporotrichosis developed acute renal failure immediately following the administration of amphotericin B on four separate occasions. The abruptness of the renal failure and its reversibility within days suggests that there was a functional component to the renal dysfunction. We propose that amphotericin, in the setting of reduced effective arterial volume, may activate tubuloglomerular feedback, thereby contributing to acute renal failure.
3827439|t|Recurrent reversible acute renal failure from amphotericin.
3827439	21	40	acute renal failure	Disease	D058186
3827439	46	58	amphotericin	Chemical	D000666
3827439	87	96	cirrhosis	Disease	D005355
3827439	114	128	sporotrichosis	Disease	D013174
3827439	139	158	acute renal failure	Disease	D058186
3827439	203	217	amphotericin B	Chemical	D000666
3827439	268	281	renal failure	Disease	D051437
3827439	370	387	renal dysfunction	Disease	D007674
3827439	405	417	amphotericin	Chemical	D000666
3827439	536	555	acute renal failure	Disease	D058186
3827439	induced	D000666	D058186
3827439	treated	D000666	D013174
3827439	induced	D000666	D051437
3827439	induced	D000666	D007674
4008111|a|We observed sinoatrial block due to chronic amiodarone administration in a 5-year-old boy with primary cardiomyopathy, Wolff-Parkinson-White syndrome and supraventricular tachycardia. Reduction in the dosage of amiodarone resulted in the disappearance of the sinoatrial block and the persistence of asymptomatic sinus bradycardia.
4008111|t|Amiodarone-induced sinoatrial block.
4008111	0	10	Amiodarone	Chemical	D000638
4008111	19	35	sinoatrial block	Disease	D012848
4008111	49	65	sinoatrial block	Disease	D012848
4008111	81	91	amiodarone	Chemical	D000638
4008111	132	154	primary cardiomyopathy	Disease	D009202
4008111	156	186	Wolff-Parkinson-White syndrome	Disease	D014927
4008111	191	219	supraventricular tachycardia	Disease	D013617
4008111	248	258	amiodarone	Chemical	D000638
4008111	296	312	sinoatrial block	Disease	D012848
4008111	349	366	sinus bradycardia	Disease	D012804
4008111	induced	D000638	D012848
4008111	induced	D000638	D012804
4008111	treated	D000638	D014927
4008111	treated	D000638	D013617
4071154|a|We have reported a case of acute oliguric renal failure with hyperkalemia in a patient with cirrhosis, ascites, and cor pulmonale after indomethacin therapy. Prompt restoration of renal function followed drug withdrawal, while re-exposure to a single dose of indomethacin caused recurrence of acute reversible oliguria. Our case supports the hypothesis that endogenous renal prostaglandins play a role in the maintenance of renal blood flow when circulating plasma volume is diminished. Since nonsteroidal anti-inflammatory agents interfere with this compensatory mechanism and may cause acute renal failure, they should be used with caution in such patients.
4071154|t|Indomethacin-induced renal insufficiency: recurrence on rechallenge.
4071154	0	12	Indomethacin	Chemical	D007213
4071154	21	40	renal insufficiency	Disease	D051437
4071154	111	124	renal failure	Disease	D051437
4071154	130	142	hyperkalemia	Disease	D006947
4071154	161	170	cirrhosis	Disease	D005355
4071154	172	179	ascites	Disease	D001201
4071154	185	198	cor pulmonale	Disease	D011660
4071154	205	217	indomethacin	Chemical	D007213
4071154	328	340	indomethacin	Chemical	D007213
4071154	379	387	oliguria	Disease	D009846
4071154	444	458	prostaglandins	Chemical	D011453
4071154	657	676	acute renal failure	Disease	D058186
4071154	induced	D007213	D051437
4071154	induced	D007213	D058186
4071154	induced	D007213	D006947
4071154	treated	D007213	D005355
4071154	treated	D007213	D001201
4071154	treated	D007213	D011660
4071154	induced	D007213	D009846
4071154	treated	D011453	D058186
4071154	treated	D011453	D051437
4071154	treated	D011453	D009846
435349|a|Suxamethonium chloride (Sch) was administered i.v. to 36 adult males at six rates: 0.25 mg s-1 to 20 mg s-1. The infusion was discontinued either when there was no muscular response to tetanic stimulation of the ulnar nerve or when Sch 120 mg was exceeded. Six additional patients received a 30-mg i.v. bolus dose. Fasciculations in six areas of the body were scored from 0 to 3 and summated as a total fasciculation score. The times to first fasciculation, twitch suppression and tetanus suppression were inversely related to the infusion rates. Fasciculations in the six areas and the total fasciculation score were related directly to the rate of infusion. Total fasciculation scores in the 30-mg bolus group and the 5-mg s-1 and 20-mg s-1 infusion groups were not significantly different.
435349|t|Suxamethonium infusion rate and observed fasciculations. A dose-response study.
435349	0	13	Suxamethonium	Chemical	D013390
435349	41	55	fasciculations	Disease	D005207
435349	80	102	Suxamethonium chloride	Chemical	D013390
435349	104	107	Sch	Chemical	D013390
435349	265	272	tetanic	Disease	D013746
435349	312	315	Sch	Chemical	D013390
435349	395	409	Fasciculations	Disease	D005207
435349	483	496	fasciculation	Disease	D005207
435349	523	536	fasciculation	Disease	D005207
435349	538	544	twitch	Disease	D013746
435349	561	568	tetanus	Disease	D013746
435349	627	641	Fasciculations	Disease	D005207
435349	673	686	fasciculation	Disease	D005207
435349	746	759	fasciculation	Disease	D005207
435349	induced	D013390	D005207
435349	treated	D013390	D013746
4812392|a|Azathioprine treatment benefited 19 (66%) out of 29 patients suffering from severe psoriasis. Haematological complications were not troublesome and results of biochemical liver function tests remained normal. Minimal cholestasis was seen in two cases and portal fibrosis of a reversible degree in eight. Liver biopsies should be undertaken at regular intervals if azathioprine therapy is continued so that structural liver damage may be detected at an early and reversible stage.
4812392|t|Treatment of psoriasis with azathioprine.
4812392	13	22	psoriasis	Disease	D011565
4812392	28	40	azathioprine	Chemical	D001379
4812392	42	54	Azathioprine	Chemical	D001379
4812392	125	134	psoriasis	Disease	D011565
4812392	259	270	cholestasis	Disease	D002779
4812392	304	312	fibrosis	Disease	D005355
4812392	406	418	azathioprine	Chemical	D001379
4812392	459	471	liver damage	Disease	D056486
4812392	treated	D001379	D011565
4812392	induced	D001379	D002779
4812392	induced	D001379	D005355
4812392	induced	D001379	D056486
603022|a|Galanthamine hydrobromide, an anticholinesterase drug capable of penetrating the blood-brain barrier, was used in a patient demonstrating central effects of scopolamine (hyoscine) overdosage. It is longer acting than physostigmine and is used in anaesthesia to reverse the non-depolarizing neuromuscular block. However, studies into the dose necessary to combating scopolamine intoxication are indicated.
603022|t|Galanthamine hydrobromide, a longer acting anticholinesterase drug, in the treatment of the central effects of scopolamine (Hyoscine).
603022	0	25	Galanthamine hydrobromide	Chemical	D005702
603022	111	122	scopolamine	Chemical	D012601
603022	124	132	Hyoscine	Chemical	D012601
603022	135	160	Galanthamine hydrobromide	Chemical	D005702
603022	292	303	scopolamine	Chemical	D012601
603022	305	313	hyoscine	Chemical	D012601
603022	315	325	overdosage	Disease	D062787
603022	352	365	physostigmine	Chemical	D010830
603022	500	511	scopolamine	Chemical	D012601
603022	induced	D012601	D062787
603022	treated	D005702	D062787
6103707|a|Flunitrazepam 0.5, 1.0 or 2.0 mg was given by the oral or i.m. routes to groups of volunteers and its effects compared. Plasma concentrations of the drug were estimated by gas-liquid chromatography, in a smaller number of the subjects. The most striking effect was sedation which increased with the dose, 2 mg producing deep sleep although the subjects could still be aroused. The effects of i.m. administration were apparent earlier and sometimes lasted longer than those following oral administration. Dizziness was less marked than sedation, but increased with the dose. There was pain on i.m. injection of flunitrazepam significantly more often than with isotonic saline. Plasma concentrations varied with dose and route and corresponded qualitatively with the subjective effects. The drug was still present in measurable quantities after 24 h even with the smallest dose.
6103707|t|Comparison of the subjective effects and plasma concentrations following oral and i.m. administration of flunitrazepam in volunteers.
6103707	105	118	flunitrazepam	Chemical	D005445
6103707	134	147	Flunitrazepam	Chemical	D005445
6103707	638	647	Dizziness	Disease	D004244
6103707	718	722	pain	Disease	D010146
6103707	744	757	flunitrazepam	Chemical	D005445
6103707	induced	D005445	D004244
6103707	induced	D005445	D010146
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|t|Development of isoproterenol-induced cardiac hypertrophy.
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	induced	D007545	D006965
6203632	induced	D007545	D006984
6203632	induced	D006909	D006965
6203632	induced	D007545	D006332
6203632	induced	D006909	D006332
6203632	induced	D006909	D006984
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|t|Multiple side effects of penicillamine therapy in one patient with rheumatoid arthritis.
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	induced	D010396	C536202
6216862	induced	D010396	D005076
6216862	induced	D010396	D011507
6216862	induced	D010396	D008180
6216862	induced	D010396	D017285
6216862	induced	D010396	D009157
6216862	induced	D010396	D012871
6229975|a|The effect of long-term timolol treatment on heart size after myocardial infarction was evaluated by X-ray in a double-blind study including 241 patients (placebo 126, timolol 115). The follow-up period was 12 months. The timolol-treated patients showed a small but significant increase in heart size from baseline in contrast to a decrease in the placebo group. These differences may be caused by timolol-induced bradycardia and a compensatory increase in end-diastolic volume. The timolol-related increase in heart size was observed only in patients with normal and borderline heart size. In patients with cardiomegaly, the increase in heart size was similar in both groups. After re-infarction, heart size increased in the placebo group and remained unchanged in the timolol group.
6229975|t|Changes in heart size during long-term timolol treatment after myocardial infarction.
6229975	39	46	timolol	Chemical	D013999
6229975	63	84	myocardial infarction	Disease	D009203
6229975	110	117	timolol	Chemical	D013999
6229975	148	169	myocardial infarction	Disease	D009203
6229975	254	261	timolol	Chemical	D013999
6229975	308	315	timolol	Chemical	D013999
6229975	484	491	timolol	Chemical	D013999
6229975	500	511	bradycardia	Disease	D001919
6229975	569	576	timolol	Chemical	D013999
6229975	694	706	cardiomegaly	Disease	D006332
6229975	772	782	infarction	Disease	D007238
6229975	856	863	timolol	Chemical	D013999
6229975	treated	D013999	D009203
6229975	treated	D013999	D007238
6229975	induced	D013999	D001919
6229975	Association	D013999	D006332
6287825|a|The anatomical and aetiological diagnoses of peripheral nerve disease excluding its primary benign and malignant disorders, as seen in 358 Nigerians are presented. There is a male preponderance and the peak incidence is in the fourth decade. Sensori-motor neuropathy was the commonest presentation (50%). Guillain-Barr   syndrome was the commonest identifiable cause (15.6%), accounting for half of the cases with motor neuropathy. Peripheral neuropathy due to nutritional deficiency of thiamine and riboflavin was common (10.1%) and presented mainly as sensory and sensori-motor neuropathy. Diabetes mellitus was the major cause of autonomic neuropathy. Isoniazid was the most frequent agent in drug-induced neuropathy. Migraine (20%) was not an uncommon cause of cranial neuropathy although malignancies arising from the reticuloendothelial system or related structures of the head and neck were more frequent (26%). In 26.5% of all the cases, the aetiology of the neuropathy was undetermined. Heredofamilial and connective tissue disorders were rare. Some of the factors related to the clinical presentation and pathogenesis of the neuropathies are briefly discussed.
6287825|t|Diseases of peripheral nerves as seen in the Nigerian African.
6287825	0	29	Diseases of peripheral nerves	Disease	D010523
6287825	108	132	peripheral nerve disease	Disease	D010523
6287825	305	329	Sensori-motor neuropathy	Disease	D010523
6287825	368	392	Guillain-Barr   syndrome	Disease	D020275
6287825	477	493	motor neuropathy	Disease	D010523
6287825	495	516	Peripheral neuropathy	Disease	D010523
6287825	524	546	nutritional deficiency	Disease	D044342
6287825	550	558	thiamine	Chemical	D013831
6287825	563	573	riboflavin	Chemical	D012256
6287825	629	653	sensori-motor neuropathy	Disease	D010523
6287825	655	672	Diabetes mellitus	Disease	D003920
6287825	696	716	autonomic neuropathy	Disease	D009422
6287825	718	727	Isoniazid	Chemical	D007538
6287825	772	782	neuropathy	Disease	D009422
6287825	784	792	Migraine	Disease	D008881
6287825	828	846	cranial neuropathy	Disease	D003389
6287825	856	868	malignancies	Disease	D009369
6287825	1030	1040	neuropathy	Disease	D009422
6287825	1078	1105	connective tissue disorders	Disease	D003240
6287825	1198	1210	neuropathies	Disease	D009422
6287825	induced	D007538	D009422
6287825	induced	D007538	D010523
6287825	induced	D013831	D009422
6287825	induced	D012256	D009422
6287825	induced	D013831	D010523
6287825	induced	D012256	D010523
6287825	induced	D013831	D044342
6287825	induced	D012256	D044342
6503301|a|A case of veno-occlusive disease of the liver with fatal outcome after dacarbazine (DTIC) therapy for melanoma is reported. There was a fulminant clinical course from start of symptoms until death. At autopsy the liver was enlarged and firm with signs of venous congestion. Small- and medium-sized hepatic veins were blocked by thrombosis. Eosinophilic infiltrations were found around the vessels. Published cases from the literature are reviewed and pertinent features discussed.
6503301|t|Veno-occlusive liver disease after dacarbazine therapy (DTIC) for melanoma.
6503301	0	28	Veno-occlusive liver disease	Disease	D006504
6503301	35	46	dacarbazine	Chemical	D003606
6503301	56	60	DTIC	Chemical	D003606
6503301	66	74	melanoma	Disease	D008545
6503301	86	121	veno-occlusive disease of the liver	Disease	D006504
6503301	147	158	dacarbazine	Chemical	D003606
6503301	160	164	DTIC	Chemical	D003606
6503301	178	186	melanoma	Disease	D008545
6503301	267	272	death	Disease	D003643
6503301	331	348	venous congestion	Disease	D006940
6503301	404	414	thrombosis	Disease	D013927
6503301	induced	D003606	D013927
6503301	induced	D003606	D006504
6503301	treated	D003606	D008545
6503301	Association	D003606	D003643
6503301	induced	D003606	D006940
6518066|a|Cross-sectional echocardiography was used to evaluate two neonates whose mothers ingested lithium during pregnancy. In one infant, Ebstein's anomaly of the tricuspid valve was identified. In the other infant cross-sectional echocardiography provided reassurance that the infant did not have Ebstein's anomaly. Cross-sectional echocardiographic screening of newborns exposed to lithium during gestation can provide highly accurate, noninvasive assessment of the presence or absence of lithium-induced cardiac malformations.
6518066|t|Maternal lithium and neonatal Ebstein's anomaly: evaluation with cross-sectional echocardiography.
6518066	9	16	lithium	Chemical	D008094
6518066	30	47	Ebstein's anomaly	Disease	D004437
6518066	189	196	lithium	Chemical	D008094
6518066	230	247	Ebstein's anomaly	Disease	D004437
6518066	390	407	Ebstein's anomaly	Disease	D004437
6518066	476	483	lithium	Chemical	D008094
6518066	583	590	lithium	Chemical	D008094
6518066	599	620	cardiac malformations	Disease	D006331
6518066	induced	D008094	D004437
6518066	induced	D008094	D006331
6534871|a|The effects of exercise on the severity of isoproterenol-induced myocardial infarction were studied in female albino rats of 20,40,60 and 80 weeks of age. The rats were trained to swim for a specific duration and for a particular period. The occurrence of infarcts were confirmed by histological methods. Elevations in the serum GOT and GPT were maximum in the sedentary-isoproterenols and minimum in the exercise-controls. These changes in the serum transaminases were associated with corresponding depletions in the cardiac GOT and GPT. However, age was seen to interfere with the responses exhibited by the young and old rats. Studies dealing with myocardial infarction are more informative when dealt with age.
6534871|t|Effects of training on the extent of experimental myocardial infarction in aging rats.
6534871	50	71	myocardial infarction	Disease	D009203
6534871	130	143	isoproterenol	Chemical	D007545
6534871	152	173	myocardial infarction	Disease	D009203
6534871	343	351	infarcts	Disease	D007238
6534871	458	472	isoproterenols	Chemical	D007545
6534871	738	759	myocardial infarction	Disease	D009203
6534871	induced	D007545	D009203
6534871	induced	D007545	D007238
6538499|a|The effect of a widely used organic solvent, polyethylene glycol 400 (PEG 400), on the toxic action of an acute or chronic treatment with adriamycin (ADR) was evaluated in mice. PEG 400 impressively decreased both acute high-dose and chronic low-dose-ADR-associated lethality. Light microscopic analysis showed a significant protection against ADR-induced cardiac morphological alterations. Such treatment did not diminish the ADR antitumor activity in L1210 leukemia and in Ehrlich ascites tumor.
6538499|t|Effect of polyethylene glycol 400 on adriamycin toxicity in mice.
6538499	10	33	polyethylene glycol 400	Chemical	D011092
6538499	37	47	adriamycin	Chemical	D004317
6538499	48	56	toxicity	Disease	D064420
6538499	111	134	polyethylene glycol 400	Chemical	D011092
6538499	136	143	PEG 400	Chemical	D011092
6538499	204	214	adriamycin	Chemical	D004317
6538499	216	219	ADR	Chemical	D004317
6538499	244	251	PEG 400	Chemical	D011092
6538499	317	320	ADR	Chemical	D004317
6538499	410	413	ADR	Chemical	D004317
6538499	422	455	cardiac morphological alterations	Disease	D009202
6538499	493	496	ADR	Chemical	D004317
6538499	519	533	L1210 leukemia	Disease	D007939
6538499	541	562	Ehrlich ascites tumor	Disease	D002286
6538499	treated	D011092	D064420
6538499	induced	D004317	D064420
6538499	treated	D011092	D009202
6538499	induced	D004317	D009202
6538499	treated	D004317	D007939
6538499	treated	D004317	D002286
6692345|a|The co-administration of aspirin with N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT) to rats resulted in a reduced incidence of FANFT-induced bladder carcinomas but a concomitant induction of forestomach tumors. An autoradiographic study was performed on male F-344 rats fed diet containing FANFT at a level of 0.2% and/or aspirin at a level of 0.5% to evaluate the effect of aspirin on the increased cell proliferation induced by FANFT in the forestomach and bladder. FANFT-induced cell proliferation in the bladder was significantly suppressed by aspirin co-administration after 4 weeks but not after 12 weeks. In the forestomach, and also in the liver, aspirin did not affect the FANFT-induced increase in labeling index. The present results are consistent with the carcinogenicity experiment suggesting that different mechanisms are involved in FANFT carcinogenesis in the bladder and forestomach, and that aspirin's effect on FANFT in the forestomach is not due to an irritant effect associated with increased cell proliferation. Also, there appears to be an adaptation by the rats to the chronic ingestion of aspirin.
6692345|t|Effect of aspirin on N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide-induced epithelial proliferation in the urinary bladder and forestomach of the rat.
6692345	10	17	aspirin	Chemical	D001241
6692345	21	66	N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide	Chemical	D005200
6692345	176	183	aspirin	Chemical	D001241
6692345	189	234	N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide	Chemical	D005200
6692345	236	241	FANFT	Chemical	D005200
6692345	286	291	FANFT	Chemical	D005200
6692345	300	318	bladder carcinomas	Disease	D001749
6692345	350	368	forestomach tumors	Disease	D013274
6692345	449	454	FANFT	Chemical	D005200
6692345	481	488	aspirin	Chemical	D001241
6692345	534	541	aspirin	Chemical	D001241
6692345	589	594	FANFT	Chemical	D005200
6692345	627	632	FANFT	Chemical	D005200
6692345	707	714	aspirin	Chemical	D001241
6692345	814	821	aspirin	Chemical	D001241
6692345	841	846	FANFT	Chemical	D005200
6692345	1007	1012	FANFT	Chemical	D005200
6692345	1013	1027	carcinogenesis	Disease	D063646
6692345	1069	1076	aspirin	Chemical	D001241
6692345	1089	1094	FANFT	Chemical	D005200
6692345	1273	1280	aspirin	Chemical	D001241
6692345	induced	D005200	D063646
6692345	Association	D001241	D063646
6692345	treated	D001241	D001749
6692345	induced	D001241	D013274
6692345	induced	D005200	D001749
6692345	induced	D005200	D013274
6727060|a|Abnormal involuntary movements appeared in the mouth, tongue, neck and abdomen of a 64-year-old male patient after he took metoclopramide for gastrointestinal disorder in a regimen of 30 mg per day for a total of about 260 days. The symptoms exacerbated to a maximum in a month. When the metoclopramide administration was discontinued, the abnormal movements gradually improved to a considerable extent. Attention to the possible induction of specific tardive dyskinesia is called for in the use of this drug.
6727060|t|A case of tardive dyskinesia caused by metoclopramide.
6727060	10	28	tardive dyskinesia	Disease	D004409
6727060	39	53	metoclopramide	Chemical	D008787
6727060	55	85	Abnormal involuntary movements	Disease	D004409
6727060	178	192	metoclopramide	Chemical	D008787
6727060	197	222	gastrointestinal disorder	Disease	D005767
6727060	343	357	metoclopramide	Chemical	D008787
6727060	395	413	abnormal movements	Disease	D004409
6727060	507	525	tardive dyskinesia	Disease	D004409
6727060	induced	D008787	D004409
6727060	treated	D008787	D005767
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|t|Nephrotoxic effects of aminoglycoside treatment on renal protein reabsorption and accumulation.
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	induced	D000617	D007674
6728084	induced	D005839	D007674
6728084	induced	D007612	D007674
6728084	induced	D009428	D007674
6728084	induced	D012964	D007674
6728084	induced	D011188	D007674
6747681|a|Because of the rapid systemic clearance of BCNU (1,3-bis-(2-chloroethyl)-1-nitrosourea), intra-arterial administration should provide a substantial advantage over intravenous administration for the treatment of malignant gliomas. Thirty-six patients were treated with BCNU every 6 to 8 weeks, either by transfemoral catheterization of the internal carotid or vertebral artery or through a fully implantable intracarotid drug delivery system, beginning with a dose of 200 mg/sq m body surface area. Twelve patients with Grade III or IV astrocytomas were treated after partial resection of the tumor without prior radiation therapy. After two to seven cycles of chemotherapy, nine patients showed a decrease in tumor size and surrounding edema on contrast-enhanced computerized tomography scans. In the nine responders, median duration of chemotherapy response from the time of operation was 25 weeks (range 12 to more than 91 weeks). The median duration of survival in the 12 patients was 54 weeks (range 21 to more than 156 weeks), with an 18-month survival rate of 42%. Twenty-four patients with recurrent Grade I to IV astrocytomas, whose resection and irradiation therapy had failed, received two to eight courses of intra-arterial BCNU therapy. Seventeen of these had a response or were stable for a median of 20 weeks (range 6 to more than 66 weeks). The catheterization procedure is safe, with no immediate complication in 111 infusions of BCNU. A delayed complication in nine patients has been unilateral loss of vision secondary to a retinal vasculitis. The frequency of visual loss decreased after the concentration of the ethanol diluent was lowered.
6747681|t|Intra-arterial BCNU chemotherapy for treatment of malignant gliomas of the central nervous system.
6747681	15	19	BCNU	Chemical	D002330
6747681	50	67	malignant gliomas	Disease	D005910
6747681	142	146	BCNU	Chemical	D002330
6747681	148	185	1,3-bis-(2-chloroethyl)-1-nitrosourea	Chemical	D002330
6747681	310	327	malignant gliomas	Disease	D005910
6747681	367	371	BCNU	Chemical	D002330
6747681	634	646	astrocytomas	Disease	D001254
6747681	691	696	tumor	Disease	D009369
6747681	808	813	tumor	Disease	D009369
6747681	835	840	edema	Disease	D004487
6747681	1220	1232	astrocytomas	Disease	D001254
6747681	1334	1338	BCNU	Chemical	D002330
6747681	1545	1549	BCNU	Chemical	D002330
6747681	1611	1625	loss of vision	Disease	D014786
6747681	1641	1659	retinal vasculitis	Disease	D031300
6747681	1678	1689	visual loss	Disease	D014786
6747681	1731	1738	ethanol	Chemical	D000431
6747681	induced	D002330	D014786
6747681	induced	D002330	D031300
6747681	induced	D000431	D031300
6747681	induced	D000431	D014786
6747681	treated	D002330	D005910
6747681	treated	D002330	D001254
6747681	treated	D002330	D009369
6747681	treated	D002330	D004487
6861444|a|Sodium chloride solution (0.9%) or noradrenaline in doses of 4, 12 and 36 micrograms h-1 kg-1 was infused for five consecutive days, either intrarenally (by a new technique) or intravenously into rats with one kidney removed. Intrarenal infusion of noradrenaline caused hypertension at doses which did not do so when infused intravenously. Intrarenal compared with intravenous infusion of noradrenaline caused higher plasma noradrenaline concentrations and a shift of the plasma noradrenaline concentration-blood pressure effect curve towards lower plasma noradrenaline levels. These results suggest that hypertension after chronic intrarenal noradrenaline infusion is produced by relatively higher levels of circulating noradrenaline and by triggering of an additional intrarenal pressor mechanism.
6861444|t|Blood pressure response to chronic low-dose intrarenal noradrenaline infusion in conscious rats.
6861444	55	68	noradrenaline	Chemical	D009638
6861444	97	112	Sodium chloride	Chemical	D012965
6861444	132	145	noradrenaline	Chemical	D009638
6861444	346	359	noradrenaline	Chemical	D009638
6861444	367	379	hypertension	Disease	D006973
6861444	486	499	noradrenaline	Chemical	D009638
6861444	521	534	noradrenaline	Chemical	D009638
6861444	576	589	noradrenaline	Chemical	D009638
6861444	653	666	noradrenaline	Chemical	D009638
6861444	702	714	hypertension	Disease	D006973
6861444	740	753	noradrenaline	Chemical	D009638
6861444	818	831	noradrenaline	Chemical	D009638
6861444	induced	D009638	D006973
6888657|a|Pituitary tumors were induced in F344 female rats by chronic treatment with diethylstilbestrol (DES, 8-10 mg) implanted subcutaneously in silastic capsules. Over a range of 1-150 days of DES treatment, pairs of control and DES-treated rats were sacrificed, and their pituitaries dissociated enzymatically into single-cell preparations. The cell populations were examined regarding total cell recovery correlated with gland weight, intracellular prolactin (PRL) content and subsequent release in primary culture, immunocytochemical PRL staining, density and/or size alterations via separation on Ficoll-Hypaque and by unit gravity sedimentation, and cell cycle analysis, after acriflavine DNA staining, by laser flow cytometry. Total cell yields from DES-treated pituitaries increased from 1.3 times control yields at 8 days of treatment to 58.9 times control values by day 150. Intracellular PRL content ranged from 1.9 to 9.4 times control levels, and PRL release in vitro was significantly and consistently higher than controls, after at least 8 days of DES exposure. Beyond 8 days of DES exposure, the immunochemically PRL-positive proportion of cells increased to over 50% of the total population. Increased density and/or size and PRL content were indicated for the majority of the PRL cell population in both types of separation protocols. All these effects of DES were more pronounced among previously ovariectomized animals. The data extend the findings of other investigators, further establishing the DES-induced tumor as a model for study of PRL cellular control mechanisms.
6888657|t|Characterization of estrogen-induced adenohypophyseal tumors in the Fischer 344 rat.
6888657	20	28	estrogen	Chemical	D004967
6888657	37	60	adenohypophyseal tumors	Disease	D010911
6888657	85	101	Pituitary tumors	Disease	D010911
6888657	161	179	diethylstilbestrol	Chemical	D004054
6888657	181	184	DES	Chemical	D004054
6888657	272	275	DES	Chemical	D004054
6888657	308	311	DES	Chemical	D004054
6888657	761	772	acriflavine	Chemical	D000167
6888657	835	838	DES	Chemical	D004054
6888657	1141	1144	DES	Chemical	D004054
6888657	1172	1175	DES	Chemical	D004054
6888657	1452	1455	DES	Chemical	D004054
6888657	1596	1599	DES	Chemical	D004054
6888657	1608	1613	tumor	Disease	D009369
6888657	induced	D004967	D010911
6888657	induced	D004054	D009369
6888657	induced	D004054	D010911
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|t|Fatal aplastic anemia following topical administration of ophthalmic chloramphenicol.
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	induced	D002701	D001855
7072798	induced	D002701	D005128
7072798	induced	D002701	D000741
7072798	induced	D002701	D010198
7083920|a|A case is presented of a reversible intra-Hisian block occurring under amiodarone treatment for atrial tachycardia in a patient without clear intraventricular conduction abnormalities. His bundle recordings showed an atrial tachycardia with intermittent exit block and greatly prolonged BH and HV intervals (40 and 100 msec, respectively). Thirty days after amiodarone discontinuation, His bundle electrograms showed atrial flutter without intra-Hisian or infra-Hisian delay. Amiodarone should be used with caution during long-term oral therapy in patients with or without clear intraventricular conduction defects.
7083920|t|Further observations on the electrophysiologic effects of oral amiodarone therapy.
7083920	63	73	amiodarone	Chemical	D000638
7083920	119	137	intra-Hisian block	Disease	D006327
7083920	154	164	amiodarone	Chemical	D000638
7083920	179	197	atrial tachycardia	Disease	D013617
7083920	225	266	intraventricular conduction abnormalities	Disease	D006345
7083920	300	318	atrial tachycardia	Disease	D013617
7083920	441	451	amiodarone	Chemical	D000638
7083920	500	514	atrial flutter	Disease	D001282
7083920	559	569	Amiodarone	Chemical	D000638
7083920	induced	D000638	D006327
7083920	treated	D000638	D013617
7083920	Association	D000638	D006345
7083920	treated	D000638	D001282
7088431|a|Two cases of clear cell adenocarcinoma of the vagina detected at follow-up in young women exposed in utero to diethylstilbestrol are reported. One patient, aged 23, had been followed for 2 years before carcinoma was diagnosed; the second patient, aged 22, had been seen on a regular basis for 5 years, 8 months. In both instances, suspicion of the presence of carcinoma was aroused by the palpation of a small nodule in the vaginal fornix. Hysterosalpingography was performed on both patients and, in 1 instance, an abnormal x-ray film was reflected by the gross appearance of the uterine cavity found in the surgical specimen.
7088431|t|Development of clear cell adenocarcinoma in DES-exposed offspring under observation.
7088431	15	40	clear cell adenocarcinoma	Disease	D018262
7088431	44	47	DES	Chemical	D004054
7088431	98	123	clear cell adenocarcinoma	Disease	D018262
7088431	98	137	clear cell adenocarcinoma of the vagina	Disease	-1
7088431	109	137	adenocarcinoma of the vagina	Disease	D014625
7088431	195	213	diethylstilbestrol	Chemical	D004054
7088431	287	296	carcinoma	Disease	D002277
7088431	445	454	carcinoma	Disease	D002277
7088431	induced	D004054	D018262
7088431	induced	D004054	-1
7088431	induced	D004054	D014625
7248170|a|The yield of severe cirrhosis of the liver (defined as a shrunken finely nodular liver with micronodular histology, ascites greater than 30 ml, plasma albumin less than 2.2 g/dl, splenomegaly 2-3 times normal, and testicular atrophy approximately half normal weight) after 12 doses of carbon tetrachloride given intragastrically in the phenobarbitone-primed rat was increased from 25% to 56% by giving the initial "calibrating" dose of carbon tetrachloride at the peak of the phenobarbitone-induced enlargement of the liver. At this point it was assumed that the cytochrome P450/CCl4 toxic state was both maximal and stable. The optimal rat size to begin phenobarbitone was determined as 100 g, and this size as a group had a mean maximum relative liver weight increase 47% greater than normal rats of the same body weight. The optimal time for the initial dose of carbon tetrachloride was after 14 days on phenobarbitone.
7248170|t|Phenobarbitone-induced enlargement of the liver in the rat: its relationship to carbon tetrachloride-induced cirrhosis.
7248170	0	14	Phenobarbitone	Chemical	D010634
7248170	23	47	enlargement of the liver	Disease	D006529
7248170	80	100	carbon tetrachloride	Chemical	D002251
7248170	109	118	cirrhosis	Disease	D005355
7248170	140	162	cirrhosis of the liver	Disease	D008103
7248170	236	243	ascites	Disease	D001201
7248170	299	311	splenomegaly	Disease	D013163
7248170	345	352	atrophy	Disease	D001284
7248170	405	425	carbon tetrachloride	Chemical	D002251
7248170	456	470	phenobarbitone	Chemical	D010634
7248170	556	576	carbon tetrachloride	Chemical	D002251
7248170	596	610	phenobarbitone	Chemical	D010634
7248170	619	643	enlargement of the liver	Disease	D006529
7248170	699	703	CCl4	Chemical	D002251
7248170	775	789	phenobarbitone	Chemical	D010634
7248170	985	1005	carbon tetrachloride	Chemical	D002251
7248170	1027	1041	phenobarbitone	Chemical	D010634
7248170	induced	D002251	D005355
7248170	induced	D010634	D006529
7248170	induced	D002251	D008103
7248170	induced	D010634	D008103
7248170	induced	D002251	D001201
7248170	induced	D010634	D001201
7248170	induced	D002251	D013163
7248170	induced	D010634	D013163
7248170	induced	D002251	D001284
7248170	induced	D010634	D001284
7265370|a|A case of triamterene nephrolithiasis is reported in a man after 4 years of hydrochlorothiazide-triamterene therapy for hypertension. The stone passed spontaneously and was found to contain a triamterene metabolite admixed with uric acid salts. Factors affecting triamterene nephrolithiasis are discussed and 2 previously reported cases are reviewed.
7265370|t|Triamterene nephrolithiasis complicating dyazide therapy.
7265370	0	11	Triamterene	Chemical	D014223
7265370	12	27	nephrolithiasis	Disease	D053040
7265370	41	48	dyazide	Chemical	C020743
7265370	68	79	triamterene	Chemical	D014223
7265370	80	95	nephrolithiasis	Disease	D053040
7265370	134	165	hydrochlorothiazide-triamterene	Chemical	C020743
7265370	178	190	hypertension	Disease	D006973
7265370	250	261	triamterene	Chemical	D014223
7265370	286	301	uric acid salts	Chemical	D014527|D012492
7265370	321	332	triamterene	Chemical	D014223
7265370	333	348	nephrolithiasis	Disease	D053040
7265370	induced	D014527|D012492	D053040
7265370	induced	D014223	D053040
7265370	treated	D014223	D006973
7265370	induced	C020743	D053040
7265370	treated	C020743	D006973
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|t|Dose-effect and structure-function relationships in doxorubicin cardiomyopathy.
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	induced	D004317	D009202
7423039|a|The cardiotoxic effects of adriamycin were studied in mammalian myocardial cells in culture as a model system. Adriamycin inhibited cell growth and the rhythmic contractions characteristic of myocardial cells in culture. A possible involvement of energy metabolism was suggested previously, and in this study the adenylate energy charge and phosphorylcreatine mole fraction were determined in the adriamycin-treated cells. The adenylate energy charge was found to be significantly decreased, while the phophorylcreatine mole fraction was unchanged. Such disparity suggests an inhibition of creatine phosphokinase. The addition of 1 mM adenosine to the myocardial cell cultures markedly increases the ATP concentration through a pathway reportedly leading to a compartmentalized ATP pool. In the adriamycin-treated cells, the addition of adenosine increased the adenylate charge and, concomitant with this inrcease, the cells' functional integrity, in terms of percentage of beating cells and rate of contractions, was maintained.
7423039|t|Metabolic involvement in adriamycin cardiotoxicity.
7423039	25	35	adriamycin	Chemical	D004317
7423039	36	50	cardiotoxicity	Disease	D066126
7423039	56	67	cardiotoxic	Disease	D066126
7423039	79	89	adriamycin	Chemical	D004317
7423039	163	173	Adriamycin	Chemical	D004317
7423039	393	411	phosphorylcreatine	Chemical	D010725
7423039	449	459	adriamycin	Chemical	D004317
7423039	554	571	phophorylcreatine	Chemical	D010725
7423039	642	650	creatine	Chemical	D003401
7423039	687	696	adenosine	Chemical	D000241
7423039	752	755	ATP	Chemical	D000255
7423039	830	833	ATP	Chemical	D000255
7423039	847	857	adriamycin	Chemical	D004317
7423039	889	898	adenosine	Chemical	D000241
7423039	treated	D000255	D066126
7423039	induced	D004317	D066126
7423039	Association	D003401	D066126
7423039	treated	D000241	D066126
7444978|a|Streptomycin sulfate (300 mg/kg s.c.) was injected for various periods into preweanling rats and for 3 weeks into weanling rats. Beginning at 8 days of age, body movement and hearing were examined for 6 and up to 17 weeks, respectively. Abnormal movements and deafness occurred only in rats treated during the preweaning period; within this period the greatest sensitivities for these abnormalities occurred from 2 to 11-17 and 5 to 11 days of age, respectively, indicating that the cochlea is more sensitive to streptomycin than the site (vestibular or central) responsible for the dyskinesias.
7444978|t|Age-dependent sensitivity of the rat to neurotoxic effects of streptomycin.
7444978	40	50	neurotoxic	Disease	D020258
7444978	62	74	streptomycin	Chemical	D013307
7444978	76	88	Streptomycin	Chemical	D013307
7444978	313	331	Abnormal movements	Disease	D004409
7444978	336	344	deafness	Disease	D003638
7444978	588	600	streptomycin	Chemical	D013307
7444978	659	670	dyskinesias	Disease	D004409
7444978	induced	D013307	D020258
7444978	induced	D013307	D004409
7444978	induced	D013307	D003638
7449470|a|Cardiac toxicity is a major complication which limits the use of adriamycin as a chemotherapeutic agent. Cardiomyopathy is frequent when the total dose exceeds 600 mg/m2 and occurs within one to six months after cessation of therapy. A patient is reported who developed progressive cardiomyopathy two and one-half years after receiving 580 mg/m2 which apparently represents late, late cardiotoxicity.
7449470|t|Late, late doxorubicin cardiotoxicity.
7449470	11	22	doxorubicin	Chemical	D004317
7449470	23	37	cardiotoxicity	Disease	D066126
7449470	39	55	Cardiac toxicity	Disease	D066126
7449470	104	114	adriamycin	Chemical	D004317
7449470	144	158	Cardiomyopathy	Disease	D009202
7449470	321	335	cardiomyopathy	Disease	D009202
7449470	424	438	cardiotoxicity	Disease	D066126
7449470	induced	D004317	D066126
7449470	induced	D004317	D009202
7504976|a|OBJECTIVE: This study was conducted to assess the occurrence of hepatic adverse effects encountered with antithyroid drugs. METHODS: Retrospective review of medical records of 236 patients with hyperthyroidism admitted in our department (in- or out-patients) from 1986 to 1992. RESULTS: Four patients (1.7%) were identified with toxic hepatitis which could reasonably be attributed to the use of antithyroid agent. Two patients had a cholestatic hepatitis induced by carbimazole (N  omercazole). Two others had a mixed (cholestatic and cytolytic) hepatitis following carbimazole. One of the latter two patients further experienced a cytolytic hepatitis which appeared after Benzylthiouracil (Basd  ne) had replaced carbimazole. Biological features of hepatitis disappeared in all cases after cessation of the incriminated drug, while biliary, viral and immunological searches were negative. Only 2 patients of our retrospective study experienced a mild or severe neutropenia. CONCLUSION: Toxic hepatitis is a potential adverse effect of antithyroid drugs which warrants, as for haematological disturbances, a pre-therapeutic determination and a careful follow-up of relevant biological markers. Moreover, hepatotoxicity may not be restricted to one class of antithyroid agents.
7504976|t|Toxic hepatitis induced by antithyroid drugs: four cases including one with cross-reactivity between carbimazole and benzylthiouracil.
7504976	0	15	Toxic hepatitis	Disease	D056486
7504976	101	112	carbimazole	Chemical	D002231
7504976	117	133	benzylthiouracil	Chemical	C019269
7504976	199	222	hepatic adverse effects	Disease	D056486
7504976	329	344	hyperthyroidism	Disease	D006980
7504976	464	479	toxic hepatitis	Disease	D056486
7504976	569	590	cholestatic hepatitis	Disease	-1
7504976	569	580	cholestatic	Disease	D002779
7504976	581	590	hepatitis	Disease	D056486
7504976	602	613	carbimazole	Chemical	D002231
7504976	615	628	N  omercazole	Chemical	D002231
7504976	655	666	cholestatic	Disease	D002779
7504976	682	691	hepatitis	Disease	D056486
7504976	702	713	carbimazole	Chemical	D002231
7504976	778	787	hepatitis	Disease	D056486
7504976	809	825	Benzylthiouracil	Chemical	C019269
7504976	827	835	Basd  ne	Chemical	C019269
7504976	850	861	carbimazole	Chemical	D002231
7504976	886	895	hepatitis	Disease	D056486
7504976	1098	1109	neutropenia	Disease	D009503
7504976	1123	1138	Toxic hepatitis	Disease	D056486
7504976	1340	1354	hepatotoxicity	Disease	D056486
7504976	induced	D002231	D056486
7504976	induced	C019269	D056486
7504976	Association	C019269	D009503
7504976	Association	D002231	D009503
7504976	treated	D002231	D006980
7504976	induced	D002231	-1
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|t|Acute renal toxicity of doxorubicin (adriamycin)-loaded cyanoacrylate nanoparticles.
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	induced	D004317	D011507
7724492	induced	D004317	D009401
7724492	induced	D004317	D007674
7834920|a|This case study reveals an unusual finding of rapidly proliferative crescentic glomerulonephritis in a patient treated with rifampin who had no other identifiable causes for developing this disease. This patient underwent a 10-month regimen of rifampin and isoniazid for pulmonary tuberculosis and was discovered to have developed signs of severe renal failure five weeks after completion of therapy. Renal biopsy revealed severe glomerulonephritis with crescents, electron dense fibrillar deposits and moderate lymphocytic interstitial infiltrate. Other possible causes of rapidly progressive glomerulonephritis were investigated and ruled out. This report documents the unusual occurrence of rapidly progressive glomerulonephritis with crescents and fibrillar glomerulonephritis in a patient treated with rifampin.
7834920|t|Crescentic fibrillary glomerulonephritis associated with intermittent rifampin therapy for pulmonary tuberculosis.
7834920	22	40	glomerulonephritis	Disease	D005921
7834920	70	78	rifampin	Chemical	D012293
7834920	91	113	pulmonary tuberculosis	Disease	D014397
7834920	194	212	glomerulonephritis	Disease	D005921
7834920	239	247	rifampin	Chemical	D012293
7834920	359	367	rifampin	Chemical	D012293
7834920	372	381	isoniazid	Chemical	D007538
7834920	386	408	pulmonary tuberculosis	Disease	D014397
7834920	462	475	renal failure	Disease	D051437
7834920	545	563	glomerulonephritis	Disease	D005921
7834920	709	727	glomerulonephritis	Disease	D005921
7834920	829	847	glomerulonephritis	Disease	D005921
7834920	877	895	glomerulonephritis	Disease	D005921
7834920	922	930	rifampin	Chemical	D012293
7834920	induced	D012293	D005921
7834920	treated	D012293	D014397
7834920	induced	D012293	D051437
7834920	treated	D007538	D014397
7881871|a|Reactive oxygen species have been implicated in the pathogenesis of acute puromycin aminonucleoside (PAN)-induced nephropathy, with antioxidants significantly reducing the proteinuria. The temporal relationship between lipid peroxidation in the kidney and proteinuria was examined in this study. Rats were treated with a single IV injection of puromycin aminonucleoside, (PAN, 7.5 mg/kg) and 24 hour urine samples were obtained prior to sacrifice on days 3,5,7,10,17,27,41 (N = 5-10 per group). The kidneys were removed, flushed with ice cold TRIS buffer. Kidney cortices from each animal were used to prepare homogenates. Tissue lipid peroxidation was measured in whole homogenates as well as in lipid extracts from homogenates as thiobarbituric acid reactive substances. Proteinuria was evident at day 5, peaked at day 7 and persisted to day 27. Lipid peroxidation in homogenates was maximal at day 3 and declined rapidly to control levels by day 17. This study supports the role of lipid peroxidation in mediating the proteinuric injury in PAN nephropathy.
7881871|t|Time course of lipid peroxidation in puromycin aminonucleoside-induced nephropathy.
7881871	37	62	puromycin aminonucleoside	Chemical	D011692
7881871	71	82	nephropathy	Disease	D007674
7881871	93	99	oxygen	Chemical	D010100
7881871	158	183	puromycin aminonucleoside	Chemical	D011692
7881871	185	188	PAN	Chemical	D011692
7881871	198	209	nephropathy	Disease	D007674
7881871	256	267	proteinuria	Disease	D011507
7881871	340	351	proteinuria	Disease	D011507
7881871	428	453	puromycin aminonucleoside	Chemical	D011692
7881871	456	459	PAN	Chemical	D011692
7881871	816	835	thiobarbituric acid	Chemical	C029684
7881871	857	868	Proteinuria	Disease	D011507
7881871	1105	1123	proteinuric injury	Disease	D011507
7881871	1127	1130	PAN	Chemical	D011692
7881871	1131	1142	nephropathy	Disease	D007674
7881871	Association	D010100	D007674
7881871	Association	D010100	D011507
7881871	induced	D011692	D007674
7881871	induced	D011692	D011507
7930386|a|The present study was undertaken to examine the role of sleep disturbance, induced by clomipramine administration, on the secretory rate of prolactin (PRL) in addition to the direct drug effect. Two groups of supine subjects were studied under placebo-controlled conditions, one during the night, when sleeping (n = 7) and the other at daytime, when awake (n = 6). Each subject received a single 50 mg dose of clomipramine given orally 2 hours before blood collection. Plasma PRL concentrations were analysed at 10 min intervals and underlying secretory rates calculated by a deconvolution procedure. For both experiments the drug intake led to significant increases in PRL secretion, acting preferentially on tonic secretion as pulse amplitude and frequency did not differ significantly from corresponding control values. During the night clomipramine ingestion altered the complete sleep architecture in that it suppressed REM sleep and the sleep cycles and induced increased wakefulness. As the relative increase in PRL secretion expressed as a percentage of the mean did not significantly differ between the night and day time studies (46 +/- 19% vs 34 +/- 10%), it can be concluded that the observed sleep disturbance did not interfere with the drug action per se. The presence of REM sleep was shown not to be a determining factor either for secretory pulse amplitude and frequency, as, for both, mean nocturnal values were similar with and without prior clomipramine ingestion.
7930386|t|Clomipramine-induced sleep disturbance does not impair its prolactin-releasing action.
7930386	0	12	Clomipramine	Chemical	D002997
7930386	21	38	sleep disturbance	Disease	D012893
7930386	143	160	sleep disturbance	Disease	D012893
7930386	173	185	clomipramine	Chemical	D002997
7930386	497	509	clomipramine	Chemical	D002997
7930386	927	939	clomipramine	Chemical	D002997
7930386	1292	1309	sleep disturbance	Disease	D012893
7930386	1548	1560	clomipramine	Chemical	D002997
7930386	induced	D002997	D012893
7988234|a|A 72-year-old woman was admitted to the hospital with "flash" pulmonary edema, preceded by chest pain, requiring intubation. Her medical history included coronary artery disease with previous myocardial infarctions, hypertension, and diabetes mellitus. A history of angioedema secondary to lisinopril therapy was elicited. Current medications did not include angiotensin-converting enzyme inhibitors or beta-blockers. She had no previous beta-blocking drug exposure. During the first day of hospitalization (while intubated), intravenous metoprolol was given, resulting in severe angioedema. The angioedema resolved after therapy with intravenous steroids and diphenhydramine hydrochloride.
7988234|t|Angioedema following the intravenous administration of metoprolol.
7988234	0	10	Angioedema	Disease	D000799
7988234	55	65	metoprolol	Chemical	D008790
7988234	129	144	pulmonary edema	Disease	D011654
7988234	158	168	chest pain	Disease	D002637
7988234	221	244	coronary artery disease	Disease	D003324
7988234	259	281	myocardial infarctions	Disease	D009203
7988234	283	295	hypertension	Disease	D006973
7988234	301	318	diabetes mellitus	Disease	D003920
7988234	333	343	angioedema	Disease	D000799
7988234	357	367	lisinopril	Chemical	D017706
7988234	426	437	angiotensin	Chemical	D000809
7988234	605	615	metoprolol	Chemical	D008790
7988234	647	657	angioedema	Disease	D000799
7988234	663	673	angioedema	Disease	D000799
7988234	714	722	steroids	Chemical	D013256
7988234	727	742	diphenhydramine	Chemical	D004155
7988234	induced	D008790	D000799
7988234	induced	D017706	D000799
7988234	Association	D000809	D000799
7988234	Association	D008790	D006973
7988234	treated	D013256	D000799
7988234	treated	D004155	D000799
7988234	Association	D017706	D006973
8170551|a|Carbonic anhydrase inhibitors can cause nephrolithiasis. We studied 20 patients receiving long-term carbonic anhydrase inhibitor treatment for periodic paralysis and myotonia. Three patients on acetazolamide (15%) developed renal calculi. Extracorporeal lithotripsy successfully removed a renal calculus in one patient and surgery removed a staghorn calculus in another, permitting continued treatment. Renal function remained normal in all patients. Nephrolithiasis is a complication of acetazolamide but does not preclude its use.
8170551|t|Acetazolamide-induced nephrolithiasis: implications for treatment of neuromuscular disorders.
8170551	0	13	Acetazolamide	Chemical	D000086
8170551	22	37	nephrolithiasis	Disease	D053040
8170551	69	92	neuromuscular disorders	Disease	D009468
8170551	134	149	nephrolithiasis	Disease	D053040
8170551	246	255	paralysis	Disease	D010243
8170551	260	268	myotonia	Disease	D009222
8170551	288	301	acetazolamide	Chemical	D000086
8170551	318	331	renal calculi	Disease	D007669
8170551	383	397	renal calculus	Disease	D007669
8170551	444	452	calculus	Disease	D002137
8170551	545	560	Nephrolithiasis	Disease	D053040
8170551	582	595	acetazolamide	Chemical	D000086
8170551	treated	D000086	D009468
8170551	induced	D000086	D053040
8170551	treated	D000086	D010243
8170551	treated	D000086	D009222
8170551	induced	D000086	D007669
8170551	induced	D000086	D002137
8231633|a|The purpose of this study was to investigate the influence of calcium channel blockers on bupivacaine-induced acute toxicity. For each of the three tested calcium channel blockers (diltiazem, verapamil and bepridil) 6 groups of mice were treated by two different doses, i.e. 2 and 10 mg/kg/i.p., or an equal volume of saline for the control group (n = 20); 15 minutes later, all the animals were injected with a single 50 mg/kg/i.p. dose of bupivacaine. The convulsant activity, the time of latency to convulse and the mortality rate were assessed in each group. The local anesthetic-induced mortality was significantly increased by the three different calcium channel blockers. The convulsant activity of bupivacaine was not significantly modified but calcium channel blockers decreased the time of latency to obtain bupivacaine-induced convulsions; this effect was less pronounced with bepridil.
8231633|t|Effects of calcium channel blockers on bupivacaine-induced toxicity.
8231633	11	18	calcium	Chemical	D002118
8231633	39	50	bupivacaine	Chemical	D002045
8231633	59	67	toxicity	Disease	D064420
8231633	131	138	calcium	Chemical	D002118
8231633	159	170	bupivacaine	Chemical	D002045
8231633	185	193	toxicity	Disease	D064420
8231633	224	231	calcium	Chemical	D002118
8231633	250	259	diltiazem	Chemical	D004110
8231633	261	270	verapamil	Chemical	D014700
8231633	275	283	bepridil	Chemical	D015764
8231633	510	521	bupivacaine	Chemical	D002045
8231633	722	729	calcium	Chemical	D002118
8231633	775	786	bupivacaine	Chemical	D002045
8231633	822	829	calcium	Chemical	D002118
8231633	887	898	bupivacaine	Chemical	D002045
8231633	907	918	convulsions	Disease	D012640
8231633	957	965	bepridil	Chemical	D015764
8231633	induced	D002045	D012640
8231633	induced	D004110	D012640
8231633	induced	D014700	D012640
8231633	induced	D015764	D012640
8231633	induced	D002045	D064420
8231633	induced	D004110	D064420
8231633	induced	D014700	D064420
8231633	induced	D015764	D064420
8386779|a|In an attempt to determine whether penile pain associated with intracorporeal injections could be due to the acidity of the medication, we performed a randomized study comparing the incidence of penile pain following intracorporeal injections with or without the addition of sodium bicarbonate to the intracorporeal medications. A total of 38 consecutive patients who presented to our clinic with impotence received 0.2 ml. of a combination of 3 drugs: 6 mg. papaverine, 100 micrograms. phentolamine and 10 micrograms. prostaglandin E1 with (pH 7.05) or without (pH 4.17) the addition of sodium bicarbonate (0.03 mEq.). Of the 19 patients without sodium bicarbonate added to the medication 11 (58%) complained of penile pain due to the medication, while only 1 of the 19 men (5%) who received sodium bicarbonate complained of penile pain. From these data we conclude that the penile pain following intracorporeal injections is most likely due to the acidity of the medication, which can be overcome by elevating the pH to a neutral level.
8386779|t|Sodium bicarbonate alleviates penile pain induced by intracavernous injections for erectile dysfunction.
8386779	0	18	Sodium bicarbonate	Chemical	D017693
8386779	30	41	penile pain	Disease	D004414
8386779	83	103	erectile dysfunction	Disease	D007172
8386779	140	151	penile pain	Disease	D004414
8386779	300	311	penile pain	Disease	D004414
8386779	380	398	sodium bicarbonate	Chemical	D017693
8386779	502	511	impotence	Disease	D007172
8386779	564	574	papaverine	Chemical	D010208
8386779	592	604	phentolamine	Chemical	D010646
8386779	624	640	prostaglandin E1	Chemical	D000527
8386779	693	711	sodium bicarbonate	Chemical	D017693
8386779	752	770	sodium bicarbonate	Chemical	D017693
8386779	818	829	penile pain	Disease	D004414
8386779	898	916	sodium bicarbonate	Chemical	D017693
8386779	931	942	penile pain	Disease	D004414
8386779	981	992	penile pain	Disease	D004414
8386779	induced	D017693	D004414
8386779	induced	D010208	D004414
8386779	induced	D010646	D004414
8386779	induced	D000527	D004414
8386779	treated	D010208	D007172
8386779	treated	D010646	D007172
8386779	treated	D000527	D007172
8410052|a|Immunohistochemistry with monoclonal antibodies against neurofilament (NF) proteins of middle and high molecular weight class, NF-M and NF-H, was used to study axonal injury in the borderzone of focal lesions in rats. Focal injury in the cortex was produced by infusion of lactate at acid pH or by stab caused by needle insertion. Infarcts in substantia nigra pars reticulata were evoked by prolonged pilocarpine-induced status epilepticus. Immunohistochemical staining for NFs showed characteristic terminal clubs of axons in the borderzone of lesions. Differences in the labelling pattern occurred with different antibodies which apparently depended on molecular weight class of NFs and phosphorylation state. These immunohistochemical changes of NFs can serve as a marker for axonal damage in various experimental traumatic or ischemic lesions.
8410052|t|Immunohistochemical studies with antibodies to neurofilament proteins on axonal damage in experimental focal lesions in rat.
8410052	73	86	axonal damage	Disease	D001480
8410052	285	298	axonal injury	Disease	D001480
8410052	349	369	injury in the cortex	Disease	D001480
8410052	398	405	lactate	Chemical	D019344
8410052	456	500	Infarcts in substantia nigra pars reticulata	Disease	D002544
8410052	526	537	pilocarpine	Chemical	D010862
8410052	546	564	status epilepticus	Disease	D013226
8410052	904	917	axonal damage	Disease	D001480
8410052	942	951	traumatic	Disease	D014947
8410052	induced	D019344	D001480
8410052	induced	D019344	D014947
8410052	induced	D010862	D002544
8410052	induced	D010862	D013226
8410052	induced	D010862	D001480
8410052	induced	D010862	D014947
8421099|a|This article reports the changes in gallbladder function examined by ultrasonography in 20 Chinese patients with active acromegaly treated with sc injection of the somatostatin analog octreotide in dosages of 300-1500 micrograms/day for a mean of 24.2 +/- 13.9 months. During treatment with octreotide, 17 patients developed sludge, 10 had gallstones, and 1 developed acute cholecystitis requiring surgery. In all of 7 patients examined acutely, gallbladder contractility was inhibited after a single 100-micrograms injection. In 8 patients followed for 24 weeks, gallbladder contractility remained depressed throughout therapy. After withdrawal of octreotide in 10 patients without gallstones, 8 patients assessed had return of normal gallbladder contractility within 1 month. In 8 of the remaining 10 patients who developed gallstones during treatment, gallbladder contractility normalized in 5 patients (3 of whom has disappearance of their stones within 3 weeks), and remained depressed in 3 (2 of whom had stones present at 6 months). Our results suggest that the suppression of gallbladder contractility is the cause of the successive formation of bile sludge, gallstones, and cholecystitis during octreotide therapy in Chinese acromegalic patients. It is therefore very important to follow the changes of gallbladder function during long-term octreotide therapy of acromegalic patients.
8421099|t|Prospective study of the long-term effects of somatostatin analog (octreotide) on gallbladder function and gallstone formation in Chinese acromegalic patients.
8421099	67	77	octreotide	Chemical	D015282
8421099	107	116	gallstone	Disease	D042882
8421099	138	149	acromegalic	Disease	D000172
8421099	280	290	acromegaly	Disease	D000172
8421099	344	354	octreotide	Chemical	D015282
8421099	451	461	octreotide	Chemical	D015282
8421099	500	510	gallstones	Disease	D042882
8421099	528	547	acute cholecystitis	Disease	D041881
8421099	724	768	gallbladder contractility remained depressed	Disease	-1
8421099	759	768	depressed	Disease	D003866
8421099	809	819	octreotide	Chemical	D015282
8421099	843	853	gallstones	Disease	D042882
8421099	986	996	gallstones	Disease	D042882
8421099	1141	1150	depressed	Disease	D003866
8421099	1327	1337	gallstones	Disease	D042882
8421099	1343	1356	cholecystitis	Disease	D002764
8421099	1364	1374	octreotide	Chemical	D015282
8421099	1394	1405	acromegalic	Disease	D000172
8421099	1510	1520	octreotide	Chemical	D015282
8421099	1532	1543	acromegalic	Disease	D000172
8421099	induced	D015282	D002764
8421099	induced	D015282	-1
8421099	treated	D015282	D000172
8421099	induced	D015282	D042882
8421099	induced	D015282	D041881
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|t|Contribution of the sympathetic nervous system to salt-sensitivity in lifetime captopril-treated spontaneously hypertensive rats.
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	treated	D002216	D006973
8586822	treated	D018738	D006973
8586822	induced	D017673	D006973
8586822	treated	D058647	D006973
8586822	induced	D012965	D006973
8586822	treated	D003000	D006973
8638206|a|Neuromuscular blocking agents (NMBAs) are often used for patients requiring prolonged mechanical ventilation. Reports of persistent paralysis after the discontinuance of these drugs have most often involved aminosteroid-based NMBAs such as vecuronium bromide, especially when used in conjunction with corticosteroids. Atracurium besylate, a short-acting benzylisoquinolinium NMBA that is eliminated independently of renal or hepatic function, has also been associated with persistent paralysis, but only when used with corticosteroids. We report a case of atracurium-related paralysis persisting for approximately 50 hours in a patient who was not treated with corticosteroids.
8638206|t|Persistent paralysis after prolonged use of atracurium in the absence of corticosteroids.
8638206	11	20	paralysis	Disease	D010243
8638206	44	54	atracurium	Chemical	D001279
8638206	222	231	paralysis	Disease	D010243
8638206	330	348	vecuronium bromide	Chemical	D014673
8638206	408	427	Atracurium besylate	Chemical	D001279
8638206	444	464	benzylisoquinolinium	Chemical	-1
8638206	574	583	paralysis	Disease	D010243
8638206	646	656	atracurium	Chemical	D001279
8638206	665	674	paralysis	Disease	D010243
8638206	induced	D001279	D010243
8638206	induced	D014673	D010243
8638206	induced	-1	D010243
8649546|a|Seven patients suffering from Parkinson's disease (PD) with severely disabling dyskinesia received low-dose propranolol as an adjunct to the currently used medical treatment. There was a significant 40% improvement in the dyskinesia score without increase of parkinsonian motor disability. Ballistic and choreic dyskinesia were markedly ameliorated, whereas dystonia was not. This study suggests that administration of low doses of beta-blockers may improve levodopa-induced ballistic and choreic dyskinesia in PD.
8649546|t|Improvement of levodopa-induced dyskinesia by propranolol in Parkinson's disease.
8649546	15	23	levodopa	Chemical	D007980
8649546	32	42	dyskinesia	Disease	D004409
8649546	46	57	propranolol	Chemical	D011433
8649546	61	80	Parkinson's disease	Disease	D010300
8649546	112	131	Parkinson's disease	Disease	D010300
8649546	133	135	PD	Disease	D010300
8649546	161	171	dyskinesia	Disease	D004409
8649546	190	201	propranolol	Chemical	D011433
8649546	304	314	dyskinesia	Disease	D004409
8649546	341	353	parkinsonian	Disease	D010300
8649546	354	370	motor disability	Disease	D009069
8649546	394	404	dyskinesia	Disease	D004409
8649546	440	448	dystonia	Disease	D004421
8649546	540	548	levodopa	Chemical	D007980
8649546	579	589	dyskinesia	Disease	D004409
8649546	593	595	PD	Disease	D010300
8649546	induced	D007980	D004409
8649546	treated	D007980	D010300
8649546	treated	D007980	D009069
8649546	treated	D011433	D004409
8752018|a|BACKGROUND: Lithium remains a first-line treatment for the acute and maintenance treatment of bipolar disorder. Although much has been written about the management of the more common adverse effects of lithium, such as polyuria and tremor, more subtle lithium side effects such as cognitive deficits, loss of creativity, and functional impairments remain understudied. This report summarizes our experience in switching bipolar patients from lithium to divalproex sodium to alleviate such cognitive and functional impairments. METHOD: Open, case series design. RESULTS: We report seven cases where substitution of lithium, either fully or partially, with divalproex sodium was extremely helpful in reducing the cognitive, motivational, or creative deficits attributed to lithium in our bipolar patients. CONCLUSION: In this preliminary report, divalproex sodium was a superior alternative to lithium in bipolar patients experiencing cognitive deficits, loss of creativity, and functional impairments.
8752018|t|Lithium-associated cognitive and functional deficits reduced by a switch to divalproex sodium: a case series.
8752018	0	7	Lithium	Chemical	D008094
8752018	19	52	cognitive and functional deficits	Disease	D003072
8752018	76	93	divalproex sodium	Chemical	D014635
8752018	122	129	Lithium	Chemical	D008094
8752018	204	220	bipolar disorder	Disease	D001714
8752018	312	319	lithium	Chemical	D008094
8752018	329	337	polyuria	Disease	D011141
8752018	342	348	tremor	Disease	D014202
8752018	362	369	lithium	Chemical	D008094
8752018	391	409	cognitive deficits	Disease	D003072
8752018	411	429	loss of creativity	Disease	D003072
8752018	435	457	functional impairments	Disease	D003072
8752018	530	537	bipolar	Disease	D001714
8752018	552	559	lithium	Chemical	D008094
8752018	563	580	divalproex sodium	Chemical	D014635
8752018	599	635	cognitive and functional impairments	Disease	D003072
8752018	724	731	lithium	Chemical	D008094
8752018	765	782	divalproex sodium	Chemical	D014635
8752018	821	866	cognitive, motivational, or creative deficits	Disease	D003072
8752018	881	888	lithium	Chemical	D008094
8752018	896	903	bipolar	Disease	D001714
8752018	954	971	divalproex sodium	Chemical	D014635
8752018	1002	1009	lithium	Chemical	D008094
8752018	1013	1020	bipolar	Disease	D001714
8752018	1043	1061	cognitive deficits	Disease	D003072
8752018	1063	1081	loss of creativity	Disease	D003072
8752018	1087	1109	functional impairments	Disease	D003072
8752018	induced	D008094	D003072
8752018	treated	D014635	D001714
8752018	treated	D014635	D003072
8752018	treated	D008094	D001714
8752018	induced	D008094	D011141
8752018	induced	D008094	D014202
891050|a|A case is reported of the hemolytic uremic syndrome (HUS) in a woman taking oral contraceptives. She was treated with heparin, dipyridamole and hemodialysis; and after more than three months, her urinary output rose above 500 ml; and six months after the onset of anuria, dialysis treatment was stopped. This case emphasizes the possibility that HUS in adults is not invariably irreversible and that, despite prolonged oliguria, recovery of renal function can be obtained. Therefore, in adult patients affected by HUS, dialysis should not be discontinued prematurely; moreover, bilateral nephrectomy, for treatment of severe hypertension and microangiopathic hemolytic anemia, should be performed with caution.
891050|t|Late recovery of renal function in a woman with the hemolytic uremic syndrome.
891050	52	77	hemolytic uremic syndrome	Disease	D006463
891050	105	130	hemolytic uremic syndrome	Disease	D006463
891050	132	135	HUS	Disease	D006463
891050	155	174	oral contraceptives	Chemical	D003276
891050	197	204	heparin	Chemical	D006493
891050	206	218	dipyridamole	Chemical	D004176
891050	343	349	anuria	Disease	D001002
891050	425	428	HUS	Disease	D006463
891050	498	506	oliguria	Disease	D009846
891050	593	596	HUS	Disease	D006463
891050	704	716	hypertension	Disease	D006973
891050	721	754	microangiopathic hemolytic anemia	Disease	D000743
891050	induced	D003276	D006463
891050	treated	D006493	D006463
891050	treated	D004176	D006463
9249847|a|In a patient with WPW syndrome and idiopathic dilated cardiomyopathy, intractable atrioventricular reentrant tachycardia (AVRT) was iatrogenically induced. QRS without preexcitation, caused by junctional escape beats after verapamil or unidirectional antegrade block of accessory pathway after catheter ablation, established frequent AVRT attack.
9249847|t|Iatrogenically induced intractable atrioventricular reentrant tachycardia after verapamil and catheter ablation in a patient with Wolff-Parkinson-White syndrome and idiopathic dilated cardiomyopathy.
9249847	35	73	atrioventricular reentrant tachycardia	Disease	D013611
9249847	80	89	verapamil	Chemical	D014700
9249847	130	160	Wolff-Parkinson-White syndrome	Disease	D014927
9249847	165	198	idiopathic dilated cardiomyopathy	Disease	D002311
9249847	218	230	WPW syndrome	Disease	D014927
9249847	235	268	idiopathic dilated cardiomyopathy	Disease	D002311
9249847	282	320	atrioventricular reentrant tachycardia	Disease	D013611
9249847	322	326	AVRT	Disease	D013611
9249847	423	432	verapamil	Chemical	D014700
9249847	534	538	AVRT	Disease	D013611
9249847	treated	D014700	D014927
9249847	induced	D014700	D013611
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|t|Neuropeptide-Y immunoreactivity in the pilocarpine model of temporal lobe epilepsy.
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	induced	D010862	D001930
9305828	induced	D010862	D004827
9305828	induced	D010862	D013226
9305828	induced	D010862	D012640
9351491|a|Risperidone is an antipsychotic drug with high affinity at dopamine D2 and serotonin 5-HT2 receptors. Previous clinical studies have proposed that risperidone's pharmacologic profile may produce improved efficacy for negative psychotic symptoms and decreased propensity for extrapyramidal side effects; features shared by so-called 'atypical' neuroleptics. To determine if routine risperidone treatment is associated with a unique degree of D2 receptor occupancy and pattern of clinical effects, we used [123I]IBZM SPECT to determine D2 occupancy in subjects treated with routine clinical doses of risperidone (n = 12) or haloperidol (n = 7). Both risperidone and haloperidol produced D2 occupancy levels between approximately 60 and 90% at standard clinical doses. There was no significant difference between occupancy levels obtained with haloperidol or risperidone. Drug-induced parkinsonism was observed in subjects treated with risperidone (42%) and haloperidol (29%) and was observed at occupancy levels above 60%. Based on these observations, it is concluded that 5-HT2 blockade obtained with risperidone at D2 occupancy rates of 60% and above does not appear to protect against the risk for extrapyramidal side effects.
9351491|t|Extrapyramidal side effects with risperidone and haloperidol at comparable D2 receptor occupancy levels.
9351491	33	44	risperidone	Chemical	D018967
9351491	49	60	haloperidol	Chemical	D006220
9351491	105	116	Risperidone	Chemical	D018967
9351491	164	172	dopamine	Chemical	D004298
9351491	180	195	serotonin 5-HT2	Chemical	D044348
9351491	252	263	risperidone	Chemical	D018967
9351491	331	349	psychotic symptoms	Disease	D011618
9351491	486	497	risperidone	Chemical	D018967
9351491	703	714	risperidone	Chemical	D018967
9351491	727	738	haloperidol	Chemical	D006220
9351491	753	764	risperidone	Chemical	D018967
9351491	769	780	haloperidol	Chemical	D006220
9351491	946	957	haloperidol	Chemical	D006220
9351491	961	972	risperidone	Chemical	D018967
9351491	974	999	Drug-induced parkinsonism	Disease	D010302
9351491	1038	1049	risperidone	Chemical	D018967
9351491	1060	1071	haloperidol	Chemical	D006220
9351491	1205	1216	risperidone	Chemical	D018967
9351491	induced	D018967	D010302
9351491	induced	D006220	D010302
9351491	treated	D018967	D011618
9522143|a|The cause of hearing loss after spinal anaesthesia is unknown. Up until now, the only factor studied has been the effect of the diameter of the spinal needle on post-operative sensorineural hearing loss. The aim of this study was to describe this hearing loss and to investigate other factors influencing the degree of hearing loss. Two groups of 22 similar patients were studied: one group received 6 mL prilocaine 2%; and the other received 3 mL bupivacaine 0.5%. Patients given prilocaine were more likely to develop hearing loss (10 out of 22) than those given bupivacaine (4 out of 22) (P < 0.05). The average hearing loss for speech frequencies was about 10 dB after prilocaine and 15 dB after bupivacaine. None of the patients complained of subjective hearing loss. Long-term follow-up of the patients was not possible.
9522143|t|The effect of different anaesthetic agents in hearing loss following spinal anaesthesia.
9522143	46	58	hearing loss	Disease	D034381
9522143	102	114	hearing loss	Disease	D034381
9522143	265	291	sensorineural hearing loss	Disease	D006319
9522143	336	348	hearing loss	Disease	D034381
9522143	408	420	hearing loss	Disease	D034381
9522143	494	504	prilocaine	Chemical	D011318
9522143	537	548	bupivacaine	Chemical	D002045
9522143	570	580	prilocaine	Chemical	D011318
9522143	609	621	hearing loss	Disease	D034381
9522143	654	665	bupivacaine	Chemical	D002045
9522143	704	716	hearing loss	Disease	D034381
9522143	762	772	prilocaine	Chemical	D011318
9522143	789	800	bupivacaine	Chemical	D002045
9522143	848	860	hearing loss	Disease	D034381
9522143	induced	D002045	D034381
9522143	induced	D011318	D006319
9522143	induced	D002045	D006319
9522143	induced	D011318	D034381
9522152|a|We describe a case of transient neurological deficit that occurred after unilateral spinal anaesthesia with 8 mg of 1% hyperbaric bupivacaine slowly injected through a 25-gauge pencil-point spinal needle. The surgery and anaesthesia were uneventful, but 3 days after surgery, the patient reported an area of hypoaesthesia over L3-L4 dermatomes of the leg which had been operated on (loss of pinprick sensation) without reduction in muscular strength. Sensation in this area returned to normal over the following 2 weeks. Prospective multicentre studies with a large population and a long follow-up should be performed in order to evaluate the incidence of this unusual side effect. However, we suggest that a low solution concentration should be preferred for unilateral spinal anaesthesia with a hyperbaric anaesthetic solution (if pencil-point needle and slow injection rate are employed), in order to minimize the risk of a localized high peak anaesthetic concentration, which might lead to a transient neurological deficit.
9522152|t|A transient neurological deficit following intrathecal injection of 1% hyperbaric bupivacaine for unilateral spinal anaesthesia.
9522152	12	32	neurological deficit	Disease	D009461
9522152	82	93	bupivacaine	Chemical	D002045
9522152	161	181	neurological deficit	Disease	D009461
9522152	259	270	bupivacaine	Chemical	D002045
9522152	512	538	loss of pinprick sensation	Disease	D012678
9522152	1135	1155	neurological deficit	Disease	D009461
9522152	induced	D002045	D009461
9522152	induced	D002045	D012678
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|t|Prolongation of the QT interval related to cisapride-diltiazem interaction.
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	induced	D020117	D008133
9545159	induced	D004110	D008133
9545159	induced	D020117	D016171
9545159	induced	D020117	D016757
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|t|Open-label assessment of levofloxacin for the treatment of acute bacterial sinusitis in adults.
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	treated	D064704	D012852
9564988	induced	D064704	D003967
9564988	induced	D064704	D005414
9564988	induced	D064704	D009325
9587734|a|The present report describes a case of cardiac arrest and subsequent death as a result of hyperkalaemia following the use of suxamethonium in a 23-year-old Malawian woman. Five days after the onset of the symptoms of meningitis, the patient aspirated stomach contents and needed endotracheal intubation. Forty seconds after injection of suxamethonium, bradycardia and cardiac arrest occurred. Attempts to resuscitate the patient were not successful. The serum level of potassium was observed to be 8.4 mequiv L-1. Apart from the reduction in the patient's level of consciousness, there were no signs of motor neurone damage or of any of the other known predisposing conditions for hyperkalaemia following the administration of suxamethonium. It is postulated that her death was caused by hypersensitivity to suxamethonium, associated with her 5-day immobilization.
9587734|t|Suxamethonium-induced cardiac arrest and death following 5 days of immobilization.
9587734	0	13	Suxamethonium	Chemical	D013390
9587734	22	36	cardiac arrest	Disease	D006323
9587734	41	46	death	Disease	D003643
9587734	122	136	cardiac arrest	Disease	D006323
9587734	152	157	death	Disease	D003643
9587734	173	186	hyperkalaemia	Disease	D006947
9587734	208	221	suxamethonium	Chemical	D013390
9587734	300	310	meningitis	Disease	D008581
9587734	420	433	suxamethonium	Chemical	D013390
9587734	435	446	bradycardia	Disease	D001919
9587734	451	465	cardiac arrest	Disease	D006323
9587734	552	561	potassium	Chemical	D011188
9587734	764	777	hyperkalaemia	Disease	D006947
9587734	810	823	suxamethonium	Chemical	D013390
9587734	851	856	death	Disease	D003643
9587734	871	887	hypersensitivity	Disease	D004342
9587734	891	904	suxamethonium	Chemical	D013390
9587734	induced	D011188	D006947
9587734	induced	D013390	D006323
9587734	induced	D013390	D006947
9587734	induced	D013390	D001919
9653867|a|Eating disorders and the associated behavioural problems and drug abuse are uncommon in pregnancy. When they do occur they are often unrecognized because of denial but when significant may pose a risk to both the mother and her fetus. This case illustrates a number of problems that may be encountered in women with eating disorders in pregnancy, including prolonged and recurrent metabolic disturbances and diuretic abuse. In particular it illustrates the derangements of thyroid function seen in pregnant women with eating disorders and reminds us that when a cause for thyrotoxicosis remains obscure, thyroxine abuse should be considered and explored.
9653867|t|Thyroxine abuse: an unusual case of thyrotoxicosis in pregnancy.
9653867	0	9	Thyroxine	Chemical	D013974
9653867	36	50	thyrotoxicosis	Disease	D013971
9653867	65	81	Eating disorders	Disease	D001068
9653867	126	136	drug abuse	Disease	D019966
9653867	381	397	eating disorders	Disease	D001068
9653867	583	599	eating disorders	Disease	D001068
9653867	637	651	thyrotoxicosis	Disease	D013971
9653867	669	678	thyroxine	Chemical	D013974
9653867	induced	D013974	D013971
9672936|a|A healthy 17-year-old male received standard intermittent doses of pethidine via a patient-controlled analgesia (PCA) pump for management of postoperative pain control. Twenty-three h postoperatively he developed a brief self-limited seizure. Both plasma pethidine and norpethidine were elevated in the range associated with clinical manifestations of central nervous system excitation. No other risk factors for CNS toxicity were identified. This method allowed frequent self-dosing of pethidine at short time intervals and rapid accumulation of pethidine and norpethidine. The routine use of pethidine via PCA even for a brief postoperative analgesia should be reconsidered.
9672936|t|Pethidine-associated seizure in a healthy adolescent receiving pethidine for postoperative pain control.
9672936	0	9	Pethidine	Chemical	D008614
9672936	21	28	seizure	Disease	D012640
9672936	63	72	pethidine	Chemical	D008614
9672936	77	95	postoperative pain	Disease	D010149
9672936	172	181	pethidine	Chemical	D008614
9672936	246	264	postoperative pain	Disease	D010149
9672936	339	346	seizure	Disease	D012640
9672936	360	369	pethidine	Chemical	D008614
9672936	374	386	norpethidine	Chemical	C002752
9672936	522	530	toxicity	Disease	D064420
9672936	592	601	pethidine	Chemical	D008614
9672936	652	661	pethidine	Chemical	D008614
9672936	666	678	norpethidine	Chemical	C002752
9672936	699	708	pethidine	Chemical	D008614
9672936	treated	D008614	D010149
9672936	induced	D008614	D012640
9672936	induced	C002752	D012640
9727773|a|Primary pulmonary hypertension is a rare, progressive and incurable disease, which has been associated with the intake of appetite suppressant drugs. The importance of this association was evaluated in Belgium while this country still had no restriction on the prescription of appetite suppressants. Thirty-five patients with primary pulmonary hypertension and 85 matched controls were recruited over 32 months (1992-1994) in Belgium. Exposure to appetite-suppressants was assessed on the basis of hospital records and standardized interview. Twenty-three of the patients had previously taken appetite suppressants, mainly fenfluramines, as compared with only 5 of the controls (66 versus 6%, p<0.0001). Five patients died before the interview, all of them had taken appetite suppressants. In 8 patients the diagnosis of primary pulmonary hypertension was uncertain, 5 of them had taken appetite suppressants. The patients who had been exposed to appetite suppressants tended to be on average more severely ill, and to have a shorter median delay between onset of symptoms and diagnosis. A policy of unrestricted prescription of appetite suppressants may lead to a high incidence of associated primary pulmonary hypertension. Intake of appetite suppressants may accelerate the progression of the disease.
9727773|t|High incidence of primary pulmonary hypertension associated with appetite suppressants in Belgium.
9727773	18	48	primary pulmonary hypertension	Disease	D006976
9727773	65	86	appetite suppressants	Chemical	D001067
9727773	99	129	Primary pulmonary hypertension	Disease	D006976
9727773	221	241	appetite suppressant	Chemical	D001067
9727773	376	397	appetite suppressants	Chemical	D001067
9727773	425	455	primary pulmonary hypertension	Disease	D006976
9727773	546	567	appetite-suppressants	Chemical	D001067
9727773	692	713	appetite suppressants	Chemical	D001067
9727773	722	735	fenfluramines	Chemical	D005277
9727773	866	887	appetite suppressants	Chemical	D001067
9727773	920	950	primary pulmonary hypertension	Disease	D006976
9727773	986	1007	appetite suppressants	Chemical	D001067
9727773	1046	1067	appetite suppressants	Chemical	D001067
9727773	1228	1249	appetite suppressants	Chemical	D001067
9727773	1293	1323	primary pulmonary hypertension	Disease	D006976
9727773	1335	1356	appetite suppressants	Chemical	D001067
9727773	induced	D005277	D006976
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|t|Stroke and cocaine or amphetamine use.
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	induced	D003042	D007511
9799166	induced	D000661	D007511
9799166	induced	D000661	D020521
9799166	induced	D003042	D020521
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|t|Chronic effects of a novel synthetic anthracycline derivative (SM-5887) on normal heart and doxorubicin-induced cardiomyopathy in beagle 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	induced	D018943	D009202
9848575	induced	D004317	D009202
9848575	treated	C055866	D009202
9848575	induced	D004317	D066126
9848575	treated	C055866	D066126
9869257|a|The effects of PG-9 (3alpha-tropyl 2-(p-bromophenyl)propionate), the acetylcholine releaser, on memory processes and nerve growth factor (NGF) synthesis were evaluated. In the mouse passive-avoidance test, PG-9 (10-30 mg/kg, i.p.), administered 20 min before the training session, prevented amnesia induced by both the non selective antimuscarinic drug scopolamine and the M1-selective antagonist S-(-)-ET-126. In the same experimental conditions, PG-9 (5-20 microg per mouse, i.c.v.) was also able to prevent antimuscarine-induced amnesia, demonstrating a central localization of the activity. At the highest effective doses, PG-9 did not produce any collateral symptoms as revealed by the Irwin test, and it did not modify spontaneous motility and inspection activity, as revealed by the hole-board test. PG-9 was also able to increase the amount of NGF secreted in vitro by astrocytes in a dose-dependent manner. The maximal NGF contents obtained by PG-9 were 17.6-fold of the control value. During culture, no morphological changes were found at effective concentrations of PG-9. The current work indicates the ability of PG-9 to induce beneficial effects on cognitive processes and stimulate activity of NGF synthesis in astroglial cells. Therefore, PG-9 could represent a potential useful drug able to improve the function of impaired cognitive processes.
9869257|t|Memory facilitation and stimulation of endogenous nerve growth factor synthesis by the acetylcholine releaser PG-9.
9869257	87	100	acetylcholine	Chemical	D000109
9869257	110	114	PG-9	Chemical	C087567
9869257	131	135	PG-9	Chemical	C087567
9869257	137	178	3alpha-tropyl 2-(p-bromophenyl)propionate	Chemical	C087567
9869257	185	198	acetylcholine	Chemical	D000109
9869257	322	326	PG-9	Chemical	C087567
9869257	407	414	amnesia	Disease	D000647
9869257	469	480	scopolamine	Chemical	D012601
9869257	513	525	S-(-)-ET-126	Chemical	C098725
9869257	564	568	PG-9	Chemical	C087567
9869257	648	655	amnesia	Disease	D000647
9869257	743	747	PG-9	Chemical	C087567
9869257	923	927	PG-9	Chemical	C087567
9869257	1069	1073	PG-9	Chemical	C087567
9869257	1194	1198	PG-9	Chemical	C087567
9869257	1242	1246	PG-9	Chemical	C087567
9869257	1371	1375	PG-9	Chemical	C087567
9869257	treated	D000109	D000647
9869257	treated	C087567	D000647
9869257	induced	D012601	D000647
9869257	induced	C098725	D000647
