B1tta/Drug-ACE huggingface dataset:
[Title]: Effects of endothelin a receptor blockade on endothelial function in patients with chronic heart failure.
[Abstract]: BACKGROUND: Chronic heart failure (CHF) is associated with impaired endothelium-dependent vasodilation and increased basal vascular tone due, in part, to elevated endothelin-1 plasma levels. In the present study, we investigated whether a reduction of vascular tone using an endothelin A receptor blocker attenuates the impairment of endothelium-dependent, flow-mediated vasodilation (FMD). METHODS AND RESULTS: Twenty-one patients with CHF randomly received either the endothelin A receptor blocker LU 135252 (30 mg/d, n=7; 300 mg/d, n=7) or a placebo (n=7). Using high-resolution ultrasound, FMD and endothelium-independent, nitroglycerin-induced dilation of the brachial artery were assessed at baseline in the 21 patients with CHF and in 11 controls and after 3 weeks treatment in the 21 patients with CHF. FMD at baseline was impaired in all 21 patients with CHF (3.2+/-2%) when compared with the 11 controls (9.7+/-4.9%; P=0.0005). In comparison with baseline, FMD significantly improved after 3 weeks of treatment with LU 135252 in all 14 patients receiving it (from 3.0+/-2.0% to 4.9+/-2.9%; P=0.04), but FMD remained unchanged with placebo. Subgroup analysis, according to different dosages, revealed a significant increase of FMD compared with baseline (from 2.4+/-1.5% to 5.5+/-2.4%; P=0.03) in the patients treated with the low-dose (30 mg/d), whereas a high dose of 300 mg/d failed to increase FMD significantly. Improvement in the high-dose group, however, may have been masked by reduced vasodilator capacity due to a significant increase in vessel size (from 4.8+/-0.4 to 5.1+/-0.7 mm; P=0.03). CONCLUSIONS: These results suggest that endothelin A receptor blockade improves FMD in CHF patients.
[Drug-Disease]: LU 135252 - CHF
[Title]: Iodine-123 MIBG imaging before treatment of heart failure with carvedilol to predict improvement of left ventricular function and exercise capacity.
[Abstract]: BACKGROUND: We examined whether cardiac sympathetic imaging with iodine-123 metaiodobenzylguanidine (MIBG) would predict improvement of left ventricular (LV) function and exercise capacity in patients with heart failure after treatment with carvedilol. METHODS AND RESULTS: Eighteen patients with heart failure and 5 control subjects underwent I-123 MIBG imaging. Heart-to-mediastinum ratios at 20 minutes and 3 hours and myocardial washout rates (WR) were measured. Of the 18 patients, 11 were randomized to receive carvedilol medication, whereas the remaining 7 received a placebo. Only the carvedilol group demonstrated a significant improvement in both heart failure functional class and LV ejection fraction (EF) 1 year after the start of medication. Within the carvedilol group, MIBG WR showed a significant inverse correlation with improvement in LVEF (rho = -0.74, P =.02). The diagnostic accuracy of WR for predicting EF response to carvedilol was 91%. WR also appeared to be inversely related to the peak oxygen consumption rate (rho = -0.65, P =.08), although this did not reach statistical significance. CONCLUSION: I-123 MIBG imaging appears useful in predicting which patients with heart failure are likely to show the most improvement in LV function and exercise capacity after carvedilol treatment. Further studies in this area appear to be warranted.
[Drug-Disease]: carvedilol - heart failure
[Title]: MERIT-HF mortality and morbidity data.
[Abstract]: This survival study was designed to address whether beta-1-blockade utilizing metoprolol CR/XL (controlled release/extended release) once daily added to standard therapy reduces mortality and morbidity in patients with decreased ejection fraction and symptoms of heart failure. Enrolled in a double-blind randomized study were 3991 patients with chronic heart failure in NYHA functional class II-IV and ejection fraction < or = 0.40 stabilized on optimal standard therapy. Randomization was preceded by a 2-week single blind placebo run-in period. The study medication was uptitrated during 8 weeks starting with 12.5 mg (NYHA functional class III-IV) or 25 mg once daily (NYHA functional class II). The target dose was 200 mg once daily. The primary endpoints were all-cause mortality and combined all-cause mortality and hospitalization (time to first event) and other objectives were cause-specific data on hospitalization, NYHA functional class and quality of life. Mean follow-up time was 1 year. All-cause mortality was reduced in the metoprolol CR/XL group compared with the placebo group, 145 versus 217 deaths, 7.2% per patient year of follow-up versus 11.0% with a relative risk of 0.66 (95% CI 0.53-0.81, nominal p = 0.00009, p adjusted for interim analysis = 0.0062). This effect was consistent across all predefined subgroups. Sudden deaths were fewer in the metoprolol group (79 versus 132 deaths), RR 0.59 (p = 0.0002). Also deaths from worsening heart failure were fewer in the metoprolol group (30 versus 58 deaths), RR 0.51 (p = 0.0023). The combined endpoint total mortality or all-cause hospitalizations was also reduced by metoprolol (641 versus 767 events), RR 0.81 (p = 0.00012). Total mortality or hospitalizations due to worsening heart failure was also reduced (311 versus 439 events), RR 0.69 (p < 0.00001). The number of hospitalizations due to worsening heart failure (317 versus 451, p < 0.00001) and days in hospital due to worsening heart failure (3401 versus 5303 days, p < 0.00001) were also reduced by metoprolol. There was also an improvement in NYHA functional class, assessed by the physicians as well as the McMaster Overall Treatment Evaluation questionnaire (OTE), assessed by the patients (p = 0.028 and p = 0.089, respectively). Permanent early discontinuation was 13.9% in the metoprolol group and 15.3% in the placebo group (RR = 0.90). In conclusion, in patients with symptomatic heart failure metoprolol CR/XL once daily improved survival by 34%, sudden death by 41%, and deaths from worsening of heart failure by 49%. In addition to improvement of survival there was also a reduced need of hospitalizations for worsening heart failure and an improved NYHA functional class and of quality of life assessed in a substudy. Metoprolol was well tolerated with no difference in early discontinuation rate from placebo treatment.
[Drug-Disease]: Metoprolol - heart failure
[Title]: Comparison between isosorbide dinitrate in aerosol and in tablet form for the treatment of hypertensive emergencies in the elderly.
[Abstract]: BACKGROUND: Isosorbide dinitrate in spray form is an effective and safe option for the treatment of hypertensive emergencies. The aim of this study was to evaluate whether isosorbide dinitrate spray is as effective and safe as treatment in tablet form for the management of hypertensive emergencies in the elderly. METHODS: Forty patients with hypertensive emergencies were randomly divided into two groups of 20 patients each. Group A received 1.25 mg isosorbide dinitrate aerosol upon arrival and a second dose 15 min later when mean systemic arterial pressure (MAP) reduction was <15% . Group B patients received a single 5 mg tablet of sublingual isosorbide dinitrate. RESULTS: Blood pressure in Group A patients decreased from 193 +/- 13/123 +/- 6.6 mmHg to 154 +/- 15/92.5 +/- 7.6 mmHg (p < 0.005), the reduction beginning 10 min after drug administration; no adverse effects were found. Two patients in Group B did not respond but for the other patients in this group blood pressure decreased from 197 +/- 10/121 +/- 7 to 154 +/- 11/90 +/- 4 mmHg, (p < 0.005), the reduction beginning 45 min after receiving the medication; 8 patients suffered headache. CONCLUSION: Our results indicate that isosorbide dinitrate aerosol is more effective than tablets for the treatment of elderly patients with hypertensive emergencies.
[Drug-Disease]: isosorbide dinitrate - hypertensive emergencies
[Title]: Therapeutic effects of pindolol and nifedipine in patients with stable angina pectoris and asymptomatic resting ischemia.
[Abstract]: A single blind randomized parallel study designed to assess the anti-anginal efficacy of pindolol and nifedipine was carried out in 42 ambulatory coronary patients with stable angina pectoris. Drug efficacy was assessed in terms of (a) pain, (b) frequency of anginal episodes, (c) nitroglycerin consumption, (d) exercise tolerance and (e) ST-segment changes. The effect of these drugs on asymptomatic resting myocardial ischemia was also assessed by means of 24-h dynamic electrocardiography (DCG). All patients were checked at weekly intervals. At the end of a 4-wk placebo period, the patients were randomly assigned either to the pindolol or nifedipine group. The treatment lasted for 45 days. During the placebo period, ischemic ECG changes and symptoms of coronary insufficiency were detected in all patients. Furthermore, 12 out of 42 patients had asymptomatic myocardial ischemia at rest. One patient from each group was dropped because of tolerance. At the end of the 45-day study, pindolol and nifedipine were equi-effective on spontaneous and effort-related angina. There were, however, some differences: increased tolerance to exercise appeared earlier with pindolol: the pindolol group showed a slightly reduced while the nifedipine group showed a slightly increased heart rate. Furthermore, nifedipine reduced or eliminated asymptomatic myocardial ischemia in 6 out of 7 patients while only 1 out of 5 improved in the pindolol group.
[Drug-Disease]: nifedipine - stable angina pectoris
[Title]: Therapeutic effects of pindolol and nifedipine in patients with stable angina pectoris and asymptomatic resting ischemia.
[Abstract]: A single blind randomized parallel study designed to assess the anti-anginal efficacy of pindolol and nifedipine was carried out in 42 ambulatory coronary patients with stable angina pectoris. Drug efficacy was assessed in terms of (a) pain, (b) frequency of anginal episodes, (c) nitroglycerin consumption, (d) exercise tolerance and (e) ST-segment changes. The effect of these drugs on asymptomatic resting myocardial ischemia was also assessed by means of 24-h dynamic electrocardiography (DCG). All patients were checked at weekly intervals. At the end of a 4-wk placebo period, the patients were randomly assigned either to the pindolol or nifedipine group. The treatment lasted for 45 days. During the placebo period, ischemic ECG changes and symptoms of coronary insufficiency were detected in all patients. Furthermore, 12 out of 42 patients had asymptomatic myocardial ischemia at rest. One patient from each group was dropped because of tolerance. At the end of the 45-day study, pindolol and nifedipine were equi-effective on spontaneous and effort-related angina. There were, however, some differences: increased tolerance to exercise appeared earlier with pindolol: the pindolol group showed a slightly reduced while the nifedipine group showed a slightly increased heart rate. Furthermore, nifedipine reduced or eliminated asymptomatic myocardial ischemia in 6 out of 7 patients while only 1 out of 5 improved in the pindolol group.
[Drug-Disease]: pindolol - stable angina pectoris
[Title]: Residual pulmonary hypertension in children after treatment with inhaled nitric oxide: a follow-up study regarding cardiopulmonary and neurological symptoms.
[Abstract]: UNLABELLED: Inhaled nitric oxide is a potent vasodilator in acute severe pulmonary hypertension and is increasingly used as rescue treatment in intensive care algorithms aiming at reducing severe hypoxaemia in neonates and children. Although the immediate effects may seem impressive, long-term outcome regarding residual pulmonary hypertension and other sequelae has been studied in only a very few patients. The aim of the present study was to evaluate residual pulmonary hypertension, cardiopulmonary or neurological symptoms in children after treatment with inhaled nitric oxide in severely hypoxaemic and/or pulmonary hypertensive mechanically ventilated children. The study was performed in four paediatric intensive care units in university hospitals in Sweden, Norway and Australia. Patients who had received inhaled nitric oxide as part of their intensive care treatment for severe hypoxaemia and/or pulmonary hypertension, and in whom 6 mo had elapsed since treatment, were included for evaluation. Thus 36 paediatric or neonatal patients were examined for circulatory, respiratory or neurological disorders with clinical examination, echocardiography, chest X-ray and a capillary blood sample. Four patients with congenital heart disease had residual pulmonary hypertension. Nine patients were receiving bronchodilators. Sixteen patients had minor (n = 15) or moderate (n = 1) changes on a chest X-ray. One patient had a possible delay in psychomotor development. CONCLUSIONS: In spite of the severity of their primary illness, we found that the overwhelming majority of the surviving children were asymptomatic and doing well. The few residual circulatory and respiratory symptoms could be related to the initial condition.
[Drug-Disease]: nitric oxide - hypoxaemia
[Title]: Residual pulmonary hypertension in children after treatment with inhaled nitric oxide: a follow-up study regarding cardiopulmonary and neurological symptoms.
[Abstract]: UNLABELLED: Inhaled nitric oxide is a potent vasodilator in acute severe pulmonary hypertension and is increasingly used as rescue treatment in intensive care algorithms aiming at reducing severe hypoxaemia in neonates and children. Although the immediate effects may seem impressive, long-term outcome regarding residual pulmonary hypertension and other sequelae has been studied in only a very few patients. The aim of the present study was to evaluate residual pulmonary hypertension, cardiopulmonary or neurological symptoms in children after treatment with inhaled nitric oxide in severely hypoxaemic and/or pulmonary hypertensive mechanically ventilated children. The study was performed in four paediatric intensive care units in university hospitals in Sweden, Norway and Australia. Patients who had received inhaled nitric oxide as part of their intensive care treatment for severe hypoxaemia and/or pulmonary hypertension, and in whom 6 mo had elapsed since treatment, were included for evaluation. Thus 36 paediatric or neonatal patients were examined for circulatory, respiratory or neurological disorders with clinical examination, echocardiography, chest X-ray and a capillary blood sample. Four patients with congenital heart disease had residual pulmonary hypertension. Nine patients were receiving bronchodilators. Sixteen patients had minor (n = 15) or moderate (n = 1) changes on a chest X-ray. One patient had a possible delay in psychomotor development. CONCLUSIONS: In spite of the severity of their primary illness, we found that the overwhelming majority of the surviving children were asymptomatic and doing well. The few residual circulatory and respiratory symptoms could be related to the initial condition.
[Drug-Disease]: nitric oxide - pulmonary hypertension
[Title]: Good prognosis of patients with acute promyelocytic leukemia who achieved second complete remission (CR) with a new retinoid, Am80, after relapse from CR induced by all-trans-retinoic acid.
[Abstract]: A new synthetic retinoid, Am80, is effective in treating acute promyelocytic leukemia relapsed from all-trans-retinoic acid-induced complete remission (CR). We report here the long-term clinical outcomes of patients who achieved second CR with Am80. Of 24 evaluable patients, 14 achieved a second CR by Am80 therapy. Of those patients, 4 relapsed within 6 months, despite subsequent consolidation chemotherapy. Six patients underwent sibling or unrelated HLA-matched allogeneic bone marrow transplantation (BMT), and 4 are alive without relase for more than 49 months after achieving second CR. Four of 8 patients who did not receive BMT are alive without relapse for more than 49 months. Promyelocytic leukemia-retinoic acid receptor alpha (PML-RAR alpha) fusion transcript was undetectable by reverse transcriptase-polymerase chain reaction in all living patients. Therefore, if patients achieve second CR with Am80 and HLA-matched donors are available, BMT is the treatment of choice. However, it is noteworthy that CR was maintained for more than 49 months in half of the patients who did not receive BMT.
[Drug-Disease]: Am80 - Promyelocytic leukemia-retinoic
[Title]: Treatment of bipolar depression with twice-weekly fluoxetine: management of antidepressant-induced mania.
[Abstract]: OBJECTIVE: To report a case of treatment of bipolar depression and management of antidepressant-induced mania with a low-dose fluoxetine regimen. CASE SUMMARY: A 59-year-old white woman was admitted involuntarily to a New York State psychiatric center with a diagnosis of bipolar (type I) disorder, mixed, with psychotic features. Initial treatment with lithium, olanzapine, and clonazepam produced a remission of manic and psychotic symptoms. However, the patient remained clinically depressed. Addition of oral fluoxetine 10 mg every morning to her medication regimen was followed 22 days later by the development of a manic state. Reduction of the fluoxetine dosage to 10 mg twice weekly was associated with the attainment of euthymia in 18 days. Thirteen days after the fluoxetine dosage reduction, the patient's fluoxetine blood concentration was 20 micrograms/L and the norfluoxetine concentration was reported as 53 micrograms/L. DISCUSSION: To our knowledge, this is the first published case that describes the association between a low-dose fluoxetine regimen and the evolution of a bipolar affective state from depression to euthymia via manic switching. The temporal synchrony of this switching with initial implementation of fluoxetine 10 mg every morning, followed by a dose reduction to 10 mg twice weekly, suggests that bipolar depressed patients are extremely sensitive to low doses of antidepressants and to incremental changes in these doses. However, it also suggests that they can respond clinically to such treatment. Furthermore, our laboratory data indicate that antidepressant blood concentrations may play a contributory role in maintaining the balance between euthymia and mania in these patients. CONCLUSIONS: Manic switching is always a concern when treating a bipolar depressed patient. Utilization of a low-dose antidepressant drug regimen may be a clinically prudent approach in such an individual.
[Drug-Disease]: olanzapine - bipolar depressed
[Title]: Treatment of bipolar depression with twice-weekly fluoxetine: management of antidepressant-induced mania.
[Abstract]: OBJECTIVE: To report a case of treatment of bipolar depression and management of antidepressant-induced mania with a low-dose fluoxetine regimen. CASE SUMMARY: A 59-year-old white woman was admitted involuntarily to a New York State psychiatric center with a diagnosis of bipolar (type I) disorder, mixed, with psychotic features. Initial treatment with lithium, olanzapine, and clonazepam produced a remission of manic and psychotic symptoms. However, the patient remained clinically depressed. Addition of oral fluoxetine 10 mg every morning to her medication regimen was followed 22 days later by the development of a manic state. Reduction of the fluoxetine dosage to 10 mg twice weekly was associated with the attainment of euthymia in 18 days. Thirteen days after the fluoxetine dosage reduction, the patient's fluoxetine blood concentration was 20 micrograms/L and the norfluoxetine concentration was reported as 53 micrograms/L. DISCUSSION: To our knowledge, this is the first published case that describes the association between a low-dose fluoxetine regimen and the evolution of a bipolar affective state from depression to euthymia via manic switching. The temporal synchrony of this switching with initial implementation of fluoxetine 10 mg every morning, followed by a dose reduction to 10 mg twice weekly, suggests that bipolar depressed patients are extremely sensitive to low doses of antidepressants and to incremental changes in these doses. However, it also suggests that they can respond clinically to such treatment. Furthermore, our laboratory data indicate that antidepressant blood concentrations may play a contributory role in maintaining the balance between euthymia and mania in these patients. CONCLUSIONS: Manic switching is always a concern when treating a bipolar depressed patient. Utilization of a low-dose antidepressant drug regimen may be a clinically prudent approach in such an individual.
[Drug-Disease]: clonazepam - bipolar depressed
[Title]: Treatment of bipolar depression with twice-weekly fluoxetine: management of antidepressant-induced mania.
[Abstract]: OBJECTIVE: To report a case of treatment of bipolar depression and management of antidepressant-induced mania with a low-dose fluoxetine regimen. CASE SUMMARY: A 59-year-old white woman was admitted involuntarily to a New York State psychiatric center with a diagnosis of bipolar (type I) disorder, mixed, with psychotic features. Initial treatment with lithium, olanzapine, and clonazepam produced a remission of manic and psychotic symptoms. However, the patient remained clinically depressed. Addition of oral fluoxetine 10 mg every morning to her medication regimen was followed 22 days later by the development of a manic state. Reduction of the fluoxetine dosage to 10 mg twice weekly was associated with the attainment of euthymia in 18 days. Thirteen days after the fluoxetine dosage reduction, the patient's fluoxetine blood concentration was 20 micrograms/L and the norfluoxetine concentration was reported as 53 micrograms/L. DISCUSSION: To our knowledge, this is the first published case that describes the association between a low-dose fluoxetine regimen and the evolution of a bipolar affective state from depression to euthymia via manic switching. The temporal synchrony of this switching with initial implementation of fluoxetine 10 mg every morning, followed by a dose reduction to 10 mg twice weekly, suggests that bipolar depressed patients are extremely sensitive to low doses of antidepressants and to incremental changes in these doses. However, it also suggests that they can respond clinically to such treatment. Furthermore, our laboratory data indicate that antidepressant blood concentrations may play a contributory role in maintaining the balance between euthymia and mania in these patients. CONCLUSIONS: Manic switching is always a concern when treating a bipolar depressed patient. Utilization of a low-dose antidepressant drug regimen may be a clinically prudent approach in such an individual.
[Drug-Disease]: lithium - bipolar depressed