B1tta/Drug-ACE huggingface dataset:
[Title]: First dose hypotension after angiotensin converting enzyme inhibitor captopril and angiotensin II blocker losartan in patients with acute myocardial infarction.
[Abstract]: BACKGROUND: First dose hypotension after the administration of an angiotensin-converting enzyme inhibitor in patients with acute myocardial infarction is one of the most important adverse events of this type of treatment. There is no information about first dose hypotension after angiotensin type 1-receptor blocker in this type of patient. AIM: To compare the first dose responses to low dose captopril and losartan in patients with acute myocardial infarction. METHODS: Single blind, randomised, multicentric, prospective study. Patients (n=320) with confirmed acute myocardial infarction, age >18 years, treated by direct percutaneous transluminal coronary angioplasty, thrombolysis and/or heparin, were randomised to receive a single dose of 6.25-12.5 mg captopril or 12.5-25 mg losartan within 24 h of hospital admission. Baseline laboratory and clinical examinations were performed before entering the study. Blood pressure monitoring started at hospital admission and continued for at least 8 h after the medication (second dose of captopril was given after 8 h). RESULTS: The maximal blood pressure fall appeared about 1 h after the first dose of captopril and 3.5 h after the first dose of losartan. Patients in the captopril group had significantly higher incidence of asymptomatic hypotension (38%) than patients treated with losartan (24%) (P<0.001). No difference in hypotension requiring a change in medication was observed. CONCLUSION: Low dose of losartan is safe for initiating therapy in patients with acute myocardial infarction within 24 h of hospital admission.
[Drug-Disease]: losartan - acute myocardial infarction
[Title]: Efficacy, adverse events, and treatment discontinuations in fluoxetine clinical studies of major depression: a meta-analysis of the 20-mg/day dose.
[Abstract]: BACKGROUND: The efficacy and safety of fluoxetine in adults with moderate-to-severe major depression are well established. However, most analyses combined dosages (20-80 mg/day) of the compound. We hypothesized that in patients taking 20 mg/day, efficacy would be maintained but the incidence of adverse events would be lower. We present a meta-analysis of efficacy and safety data for fluoxetine, 20 mg/day. METHOD: Data were from 3 double-blind studies (N = 417) that included patients with moderate-to-severe major depression (DSM-III or DSM-III-R criteria) who received placebo or fixed-dose 20-mg/day treatment with fluoxetine. Efficacy was assessed using the Hamilton Rating Scale for Depression (HAM-D; HAM-D-17 total score and anxiety/somatization, retardation, sleep disturbance, and cognitive disturbance factors) and response and remission rates. Safety assessments included treatment-emergent adverse events, reasons for discontinuation, and adverse events leading to discontinuation. Adverse events were evaluated to determine the emergence of activation and/or sedation. RESULTS: At 20 mg/day, fluoxetine-treated patients demonstrated significantly greater remission and response rates and mean changes on HAM-D-17 total score and anxiety/somatization, retardation, and cognitive disturbance factor scores than placebo-treated patients (p < .001). The incidence of specific adverse events leading to discontinuation and the frequency of study discontinuations due to adverse events were similar among fluoxetine-treated and placebo-treated patients (6.1% vs. 5.8%, p = .879). Several adverse events (insomnia, asthenia, somnolence, gastroenteritis, decreased libido, chills, and confusion) occurred significantly more frequently among fluoxetine-treated patients. A significant change in sedation, but not activation, occurred in patients in the fluoxetine 20-mg/day group compared with the placebo group. CONCLUSION: These data affirm that fluoxetine at 20 mg/day is efficacious, safe, and of similar activation potential when compared with placebo in patients with major depression.
[Drug-Disease]: fluoxetine - major depression
[Title]: Effect of indomethacin on blood pressure in elderly people with essential hypertension well controlled on amlodipine or enalapril.
[Abstract]: Arthritis and hypertension are frequent comorbidities in the elderly hypertensive population. Nonsteroidal anti-inflammatory drugs are often used to relieve pain in arthritic patients but a side effect is sodium retention and consequent elevation of blood pressure (BP). The effect of dihydropyridine calcium blocking drugs is relatively independent of sodium intake, whereas the angiotensin-converting enzyme (ACE) inhibitors' effects can be blunted by a high-sodium diet. This study compared the effects of indomethacin with placebo in elderly patients with essential hypertension who had been controlled with amlodipine or enalapril. Indomethacin 50 mg twice daily or placebo was administered for 3 weeks in a double-blind crossover study to patients controlled with amlodipine or enalapril. The response was assessed by ambulatory BP measurement. Indomethacin raised BP and lowered pulse rates in patients taking enalapril but had little effect in patients receiving amlodipine. The difference caused by indomethacin between the two groups was 10.1/4.9 mm Hg increase in BP and a 5.6 beats/min fall in pulse in people taking enalapril. Addition of indomethacin to patients taking either drug caused a rise in weight and a fall in plasma renin. It is postulated that the effect is due to inhibition of prostaglandin synthesis, which causes sodium retention. In patients taking amlodipine, the fall in plasma renin ameliorates the effect of sodium retention on BP. In patients taking enalapril, plasma renin falls but this is not translated into an effect because of the blockage of converting enzyme. Thus, the full effect of sodium retention on BP is expressed. In patients treated with indomethacin, fewer patients may respond to ACE inhibitors. However, the major problem is the patient who intermittently takes indomethacin or other nonsteroidal anti-inflammatory drugs, which, if a person is treated by an ACE inhibitor causes BP to go out of control. In such patients amlodipine would appear to be a preferred choice to enalapril.
[Drug-Disease]: enalapril - hypertension
[Title]: Effect of indomethacin on blood pressure in elderly people with essential hypertension well controlled on amlodipine or enalapril.
[Abstract]: Arthritis and hypertension are frequent comorbidities in the elderly hypertensive population. Nonsteroidal anti-inflammatory drugs are often used to relieve pain in arthritic patients but a side effect is sodium retention and consequent elevation of blood pressure (BP). The effect of dihydropyridine calcium blocking drugs is relatively independent of sodium intake, whereas the angiotensin-converting enzyme (ACE) inhibitors' effects can be blunted by a high-sodium diet. This study compared the effects of indomethacin with placebo in elderly patients with essential hypertension who had been controlled with amlodipine or enalapril. Indomethacin 50 mg twice daily or placebo was administered for 3 weeks in a double-blind crossover study to patients controlled with amlodipine or enalapril. The response was assessed by ambulatory BP measurement. Indomethacin raised BP and lowered pulse rates in patients taking enalapril but had little effect in patients receiving amlodipine. The difference caused by indomethacin between the two groups was 10.1/4.9 mm Hg increase in BP and a 5.6 beats/min fall in pulse in people taking enalapril. Addition of indomethacin to patients taking either drug caused a rise in weight and a fall in plasma renin. It is postulated that the effect is due to inhibition of prostaglandin synthesis, which causes sodium retention. In patients taking amlodipine, the fall in plasma renin ameliorates the effect of sodium retention on BP. In patients taking enalapril, plasma renin falls but this is not translated into an effect because of the blockage of converting enzyme. Thus, the full effect of sodium retention on BP is expressed. In patients treated with indomethacin, fewer patients may respond to ACE inhibitors. However, the major problem is the patient who intermittently takes indomethacin or other nonsteroidal anti-inflammatory drugs, which, if a person is treated by an ACE inhibitor causes BP to go out of control. In such patients amlodipine would appear to be a preferred choice to enalapril.
[Drug-Disease]: amlodipine - hypertension
[Title]: Evaluation of antineutrophil cytoplasmic antibody seroconversion induced by minocycline, sulfasalazine, or penicillamine.
[Abstract]: OBJECTIVE: Case reports have suggested that minocycline, sulfasalazine, and penicillamine are associated with antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis. This study evaluated ANCA seroconversion due to these agents in serum samples prospectively collected in randomized, double-blind, controlled trials. METHODS: The sources of study sera were 3 clinical trials: 1) a 48-week trial of minocycline for early rheumatoid arthritis, with 64 patients receiving minocycline compared with 68 receiving placebo; 2) a 37-week trial of sulfasalazine for rheumatoid arthritis, with 51 receiving sulfasalazine compared with 38 receiving placebo; and 3) a 104-week trial of penicillamine for early systemic sclerosis, with 15 undergoing high-dose penicillamine treatment versus 12 receiving low-dose penicillamine. ANCA were measured in the baseline and study-end serum samples by indirect immunofluorescence (IIF) for perinuclear ANCA (pANCA) and cytoplasmic ANCA (cANCA) patterns, and by antigen-specific enzyme-linked immunosorbent assay (ELISA) for antibodies to myeloperoxidase (anti-MPO) and proteinase 3 (anti-PR3). Laboratory personnel were blinded to the group identity of the samples. ANCA results were interpreted using an ANCA scoring system that combines the results of IIF and ELISA testing. RESULTS: No patient in any of the active study drug groups demonstrated ANCA seroconversion according to the final interpretation of the combined IIF and ELISA results. Twelve of the 248 patients (5%) were positive for anti-MPO with pANCA at baseline. No subject was positive for anti-PR3 with cANCA. There were no findings suggestive of vasculitis in any of these patients. CONCLUSION: From our study results, there was no suggestion of ANCA seroconversion induced by minocycline, sulfasalazine, or penicillamine. However, these findings do not rule out the possibility of rare, sporadic cases of either ANCA seroconversion or true drug-induced vasculitis with these drugs.
[Drug-Disease]: minocycline - rheumatoid arthritis
[Title]: Evaluation of antineutrophil cytoplasmic antibody seroconversion induced by minocycline, sulfasalazine, or penicillamine.
[Abstract]: OBJECTIVE: Case reports have suggested that minocycline, sulfasalazine, and penicillamine are associated with antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis. This study evaluated ANCA seroconversion due to these agents in serum samples prospectively collected in randomized, double-blind, controlled trials. METHODS: The sources of study sera were 3 clinical trials: 1) a 48-week trial of minocycline for early rheumatoid arthritis, with 64 patients receiving minocycline compared with 68 receiving placebo; 2) a 37-week trial of sulfasalazine for rheumatoid arthritis, with 51 receiving sulfasalazine compared with 38 receiving placebo; and 3) a 104-week trial of penicillamine for early systemic sclerosis, with 15 undergoing high-dose penicillamine treatment versus 12 receiving low-dose penicillamine. ANCA were measured in the baseline and study-end serum samples by indirect immunofluorescence (IIF) for perinuclear ANCA (pANCA) and cytoplasmic ANCA (cANCA) patterns, and by antigen-specific enzyme-linked immunosorbent assay (ELISA) for antibodies to myeloperoxidase (anti-MPO) and proteinase 3 (anti-PR3). Laboratory personnel were blinded to the group identity of the samples. ANCA results were interpreted using an ANCA scoring system that combines the results of IIF and ELISA testing. RESULTS: No patient in any of the active study drug groups demonstrated ANCA seroconversion according to the final interpretation of the combined IIF and ELISA results. Twelve of the 248 patients (5%) were positive for anti-MPO with pANCA at baseline. No subject was positive for anti-PR3 with cANCA. There were no findings suggestive of vasculitis in any of these patients. CONCLUSION: From our study results, there was no suggestion of ANCA seroconversion induced by minocycline, sulfasalazine, or penicillamine. However, these findings do not rule out the possibility of rare, sporadic cases of either ANCA seroconversion or true drug-induced vasculitis with these drugs.
[Drug-Disease]: penicillamine - systemic sclerosis
[Title]: Evaluation of antineutrophil cytoplasmic antibody seroconversion induced by minocycline, sulfasalazine, or penicillamine.
[Abstract]: OBJECTIVE: Case reports have suggested that minocycline, sulfasalazine, and penicillamine are associated with antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis. This study evaluated ANCA seroconversion due to these agents in serum samples prospectively collected in randomized, double-blind, controlled trials. METHODS: The sources of study sera were 3 clinical trials: 1) a 48-week trial of minocycline for early rheumatoid arthritis, with 64 patients receiving minocycline compared with 68 receiving placebo; 2) a 37-week trial of sulfasalazine for rheumatoid arthritis, with 51 receiving sulfasalazine compared with 38 receiving placebo; and 3) a 104-week trial of penicillamine for early systemic sclerosis, with 15 undergoing high-dose penicillamine treatment versus 12 receiving low-dose penicillamine. ANCA were measured in the baseline and study-end serum samples by indirect immunofluorescence (IIF) for perinuclear ANCA (pANCA) and cytoplasmic ANCA (cANCA) patterns, and by antigen-specific enzyme-linked immunosorbent assay (ELISA) for antibodies to myeloperoxidase (anti-MPO) and proteinase 3 (anti-PR3). Laboratory personnel were blinded to the group identity of the samples. ANCA results were interpreted using an ANCA scoring system that combines the results of IIF and ELISA testing. RESULTS: No patient in any of the active study drug groups demonstrated ANCA seroconversion according to the final interpretation of the combined IIF and ELISA results. Twelve of the 248 patients (5%) were positive for anti-MPO with pANCA at baseline. No subject was positive for anti-PR3 with cANCA. There were no findings suggestive of vasculitis in any of these patients. CONCLUSION: From our study results, there was no suggestion of ANCA seroconversion induced by minocycline, sulfasalazine, or penicillamine. However, these findings do not rule out the possibility of rare, sporadic cases of either ANCA seroconversion or true drug-induced vasculitis with these drugs.
[Drug-Disease]: sulfasalazine - rheumatoid arthritis
[Title]: An efficacy and cost-effectiveness analysis of combination hepatitis B immune globulin and lamivudine to prevent recurrent hepatitis B after orthotopic liver transplantation compared with hepatitis B immune globulin monotherapy.
[Abstract]: Orthotopic liver transplantation (OLT) for hepatitis B virus (HBV) infection was limited until recently by poor graft and patient outcomes caused by recurrent HBV. Long-term immunoprophylaxis with hepatitis B immune globulin (HBIG) dramatically improved post-OLT survival, but recurrent HBV still occurred in up to 36% of the recipients. More recently, combination HBIG and lamivudine has been shown to effectively prevent HBV recurrence in patients post-OLT. The aim of the current study is to determine long-term outcome and cost-effectiveness of using combination HBIG and lamivudine compared with HBIG monotherapy in patients who undergo OLT for HBV. A retrospective chart review identified 59 patients administered combination HBIG and lamivudine and 12 patients administered HBIG monotherapy as primary prophylaxis against recurrent HBV. Lamivudine, 150 mg/d, was administered orally indefinitely. HBIG was administered under a standard protocol (10,000 IU intravenously during the anhepatic phase, then 10,000 IU/d intravenously for 7 days, then 10,000 IU intravenously monthly) indefinitely. A decision-analysis model was developed to evaluate the potential economic impact of prophylaxis against HBV with combination therapy compared with monotherapy. Recurrent HBV was defined as the reappearance of hepatitis B surface antigen (HBsAg) after its initial disappearance post-OLT. In the combination-therapy group, no patient redeveloped serum HBsAg or HBV DNA during mean follow-ups of 459 and 416 days, respectively. In the monotherapy group, 3 patients (25%) had reappearance of HBsAg in serum during a mean follow-up of 663 days. Combination therapy resulted in a dominant, cost-effective strategy with an average cost-effectiveness ratio of $252,111/recurrence prevented compared with $362,570/recurrence prevented in the monotherapy strategy. Combination prophylaxis with HBIG and lamivudine is highly effective in preventing recurrent HBV, may protect against the emergence of resistant mutants, and is significantly more cost-effective than HBIG monotherapy with its associated rate of recurrent HBV.
[Drug-Disease]: lamivudine - hepatitis B
[Title]: Amikacin therapy of infections in neutropenic patients.
[Abstract]: Amikacin, a new aminoglycoside antibiotic, was utilized in the treatment of 49 cases of infection which occurred in 39 neutropenic cancer patients. Thirty-four patients (69 per cent) responded to this antibiotic. Pneumonia and septicemia were the most common types of infection treated and the response rates were 65 per cent and 75 per cent, respectively. Gram-negative bacili were responsible for 93 per cent of the identified infections and 74 per cent responded. E. coli, Ps. aeruginosa, and organisms of the Klebsiella-Enterobacter-Serratia group were the most common gram-negative bacilli causing infection. Responses were more frequent among patients who maintained higher serum concentrations of antibiotic, but the differences were not statistically significant. Patients with severe neutropenia (less than 100 neutrophils/mm3) had a response rate of 68 per cent. Toxicity was manifested as azotemia and hearing loss which occurred in 13 per cent and 6 per cent, respectively. However, toxicity was directly related to serum concentration and to the number of treatments with amikacin. This antibiotic is of potential importance because of its efficacy against gram-negative bacilli infections. Best results were obtained when sufficient drug was given as a continuous intravenous infusion to maintain serum concentrations of about 15 mu g/ml.
[Drug-Disease]: amikacin - septicemia
[Title]: Chemosensitisation of malignant melanoma by BCL2 antisense therapy.
[Abstract]: BACKGROUND: Chemoresistance of malignant melanoma has been linked to expression of the proto-oncogene BCL2. Antisense oligonucleotides (ASO) targeted against BCL2 mRNA decreased BCL2 protein concentrations, increased tumour-cell apoptosis, and led to tumour responses in a mouse xenotransplantation model when combined with systemic dacarbazine. This phase I-II clinical study investigated the combination of BCL2 ASO (augmerosen, Genasense, G3139) and dacarbazine in patients with advanced malignant melanoma expressing BCL2. METHODS: In a within-patient dose-escalation protocol, 14 patients with advanced malignant melanoma were given augmerosen intravenously or subcutaneously in daily doses of 0.6-6.5 mg/kg plus standard dacarbazine treatment (total doses up to 1000 mg/m2 per cycle). Toxicity was scored by common toxicity criteria. Plasma augmerosen concentrations were assayed by high-performance liquid chromatography. In serial tumour biopsy samples, BCL2 protein concentrations were measured by western blotting and tumour-cell apoptosis was assessed. FINDINGS: The combination regimen was well tolerated, with no dose-limiting toxicity. Haematological abnormalities were mild to moderate. Lymphopenia was common, but no febrile neutropenia occurred. Higher doses of augmerosen were associated with transient fever. Four patients had liver-function abnormalities that resolved within 1 week. Steady-state plasma concentrations of augmerosen were attained within 24 h, and increased with administered dose. By day 5, daily doses of 1.7 mg/kg and higher led to a median 40% decrease in BCL2 protein in melanoma samples compared with baseline, concomitantly with increased tumour-cell apoptosis, which was greatly increased after dacarbazine treatment. Six patients have shown antitumour responses (one complete, two partial, three minor). The estimated median survival of all patients now exceeds 12 months. INTERPRETATION: Systemic administration of augmerosen downregulated the target BCL2 protein in metastatic cancer. Such downregulation of BCL2, combined with standard anticancer therapy, offers a new approach to the treatment of patients with resistant neoplasms.
[Drug-Disease]: augmerosen - melanoma
[Title]: Effects of cisapride on corrected QT interval, heart rate, and rhythm in infants undergoing polysomnography.
[Abstract]: OBJECTIVE: To evaluate the effects of cisapride, a prokinetic gastrointestinal drug, on the electrocardiographic QT interval, heart rate, and rhythm in infants during routine 8-hour polysomnography. Reported electrocardiogram (ECG) and rhythm disturbances in a small number of patients with the use of cisapride provided the impetus for this prospective study. STUDY DESIGN: Two hundred fifty-two infants born at term were enrolled. Of these, 134 were on cisapride therapy for suspected gastroesophageal reflux and 118 were not on cisapride and served as controls. Cisapride-treated and control infants were from the outset divided into 3 age groups; group 1: under 3 months of age; group 2: between 3 and 6 months of age; and group 3: >6 months of age. Continuous ECG bipolar limb lead I recording, saturation monitoring, and electroencephalography were conducted. QT intervals and heart rate were measured at hourly intervals. RESULTS: Cisapride doses were: group 1 mean, 0.80 mg/kg/day (range: 0.38-1.55); group 2 mean, 0.80 mg/kg/day (range: 0. 23-1.38); and group 3 mean, 0.72 mg/kg/day (range: 0.32-1.41). Heart rate was higher in the younger infants, with a gradual decrease with age. No difference in heart rate was detected between the cisapride and control groups. The QTc interval in patients in group 1 was statistically longer than the controls, when applying both Bazett's and Hodges' formulae for QT correction. The other age groups did not differ. No arrhythmia or atrioventricular conduction abnormalities were observed. CONCLUSION: Infants under 3 months of age on cisapride treatment had significantly longer QTc intervals (with Bazett's formula, the 98th percentile was 504 ms in the cisapride group vs 447 ms in controls). The clinical significance and risk of the increased QTc interval in these infants are unclear and need further evaluation and risk stratification. Meanwhile, cisapride should be judiciously prescribed in infants <3 months of age.
[Drug-Disease]: cisapride - gastroesophageal reflux