B1tta/Drug-ACE huggingface dataset:
[Title]: Single copy of variant CYP2A6 alleles does not confer susceptibility to liver dysfunction in patients treated with coumarin.
[Abstract]: OBJECTIVE: Coumarin, used in the treatment of chronic venous diseases, is mainly metabolized to non-toxic 7-hydroxy-coumarin by CYP2A6. At least, 3 variant alleles, CYP2A6*2, CYP2A6*3 and CYP2A6*4A, have been shown to encode catalytically defective proteins. Sporadic elevation of liver enzymes has been reported on the chronic administration ofcoumarin. We sought to determine if susceptibility to coumarin-associated liver dysfunction is genetically determined by polymorphism in CYP2A6 and impairment of the 7-hydroxylation ofcoumarin. Additionally, we were interested in the effect of polymorphism on smoking because of the predominant role of CYP2A6 in the metabolism of nicotine. METHODS: The investigation was performed prospectively within a randomized double-blind clinical trial of the coumarin-containing drug SB-LOT (90 mg coumarin + 540 mg troxerutin/d) vs. placebo in 231 German patients with chronic venous insufficiency. Monitoring of the hepatic status involved regular measurements of liver function during the 16-week treatment. Genotyping of CYP2A6 was carried out by means of PCR and confirmed by DNA sequencing analysis. RESULTS: The allelic frequencies of the variant CYP2A6*2 and CYP2A6*3 alleles were 0.023 and 0.014, respectively. There was no significant difference in the incidence of liver dysfunction between heterozygotes with CYP2A6*2, CYP2A6*3 and wild-type homozygotes. CYP2A6 polymorphism had no significant effect on smoking behavior. CONCLUSION: No evidence was obtained that the studied polymorphism in CYP2A6 is a determinant of the coumarin-associated liver dysfunction.
[Drug-Disease]: coumarin - venous insufficiency
[Title]: Effects of zafirlukast on bronchial asthma and allergic rhinitis.
[Abstract]: Asthma and allergic rhinitis are common conditions, occurring with increasing prevalence and frequently coexist. In both conditions histamine and cysteinil leukotrienes are important pathogenic inflammatory mediators. We evaluated the effects of the leukotriene receptor antagonist zafirlukast, 20mg administered twice daily for 2 weeks, in patients with allergic rhinitis and bronchial asthma during the grass pollen season. Patients underwent skin prick testing, spirometry, rhinomanometry, mucus transport test with saccharine, nasal epithelial brushing to study ciliary beat and, finally, nasal lavage.Thirty-five subjects completed the study. At the end of the study period, zafirlukast significantly reduced asthma and rhinitis symptoms (P&lt; or =0.05); FEV(1) values were unchanged (P=0.10), whereas nasal resistances showed a decrease following treatment (P=0.01). Ciliary beat frequency (CBF) also improved (P=0.00), although mucociliary transport showed no improvement (P=0.87). The number of eosinophils in nasal lavage fluid decreased (P=0.00) while that of neutrophils was unchanged (P=0.09). These positive effects suggest that zafirlukast may be usefully employed in the treatment of both bronchial asthma, as previously demonstrated, and allergic rhinitis.
[Drug-Disease]: zafirlukast - bronchial asthma
[Title]: Desipramine and contingency management for cocaine and opiate dependence in buprenorphine maintained patients.
[Abstract]: Co-dependence on opiates and cocaine occurs in about 60% of patients entering methadone treatment and has a poor prognosis. However, we recently found that desipramine (DMI) could be combined with buprenorphine to significantly reduce combined opiate and cocaine use among these dually dependent patients. Furthermore, contingency management (CM) has been quite potent in reducing cocaine abuse during methadone maintenance. To test the efficacy of combining CM with these medications we designed a 12-week, randomized, double blind, four cell trial evaluating DMI (150 mg/day) or placebo plus CM or a non-contingent voucher control in 160 cocaine abusers maintained on buprenorphine (median 16 mg daily). Cocaine-free and combined opiate and cocaine-free urines increased more rapidly over time in those treated with either DMI or CM, and those receiving both interventions had more drug-free urines (50%) than the other three treatment groups (25-29%). Self reported opiate and cocaine use and depressive and opioid withdrawal symptoms showed no differences among the groups and symptom levels did not correlate with urine toxicology results. Lower DMI plasma levels (average 125 ng/ml) were associated with greater cocaine-free urines. DMI and CM had independent and additive effects in facilitating cocaine-free urines in buprenorphine maintained patients. The antidepressant appeared to enhance responsiveness to CM reinforcement.
[Drug-Disease]: buprenorphine - cocaine abuse
[Title]: Desipramine and contingency management for cocaine and opiate dependence in buprenorphine maintained patients.
[Abstract]: Co-dependence on opiates and cocaine occurs in about 60% of patients entering methadone treatment and has a poor prognosis. However, we recently found that desipramine (DMI) could be combined with buprenorphine to significantly reduce combined opiate and cocaine use among these dually dependent patients. Furthermore, contingency management (CM) has been quite potent in reducing cocaine abuse during methadone maintenance. To test the efficacy of combining CM with these medications we designed a 12-week, randomized, double blind, four cell trial evaluating DMI (150 mg/day) or placebo plus CM or a non-contingent voucher control in 160 cocaine abusers maintained on buprenorphine (median 16 mg daily). Cocaine-free and combined opiate and cocaine-free urines increased more rapidly over time in those treated with either DMI or CM, and those receiving both interventions had more drug-free urines (50%) than the other three treatment groups (25-29%). Self reported opiate and cocaine use and depressive and opioid withdrawal symptoms showed no differences among the groups and symptom levels did not correlate with urine toxicology results. Lower DMI plasma levels (average 125 ng/ml) were associated with greater cocaine-free urines. DMI and CM had independent and additive effects in facilitating cocaine-free urines in buprenorphine maintained patients. The antidepressant appeared to enhance responsiveness to CM reinforcement.
[Drug-Disease]: DMI - cocaine abuse
[Title]: Comparison of patient-controlled analgesia with and without a background infusion after appendicectomy in children.
[Abstract]: BACKGROUND: There have been many studies using patient-controlled analgesia (PCA) and opioids for postoperative analgesia in children. In this study, we investigated the efficacy, usefulness and analgesic consumption of two different PCA programmes [bolus dose alone (BD) or bolus dose with background infusion (BD + BI)] to evaluate postoperative analgesia for children after emergency appendicectomy. METHODS: Forty children, aged between 6 and 15 years and ASA class I or II, undergoing emergency appendicectomy were randomly allocated into two groups. The children were given a loading dose of pethidine 0.3 mg.kg-1 and 150 micro g.kg-1 bolus intravenously in group BD (n = 20) and pethidine 0.3 mg.kg-1 loading dose, 75 micro g.kg-1 bolus and 15 micro g.kg-1.h-1 background infusion in group BD + BI (n = 20). The lockout interval was 20 min in both groups. RESULTS: There were no significant differences in pain, sedation and nausea scores during the 24-h postoperative period between the groups (P > 0.05). Pethidine consumption was significantly lower in group BD + BI than that in group BD for the first 24-h period (P < 0.05). CONCLUSIONS: We demonstrated that both these PCA programmes were effective and reliable for postoperative pain relief in children. We believe that giving information about PCA to the children and their parents is useful during the preoperative period. However, the background infusion with lower bolus dose in PCA did not increase pethidine consumption.
[Drug-Disease]: pethidine - postoperative pain
[Title]: Effectiveness of aggressive management of dyslipidemia in a collaborative-care practice model.
[Abstract]: The Cardiovascular Risk Identification and Treatment Center was established in 1997, adopting a collaborative-care clinic model for the purpose of improving the management of high-risk patients with dyslipidemia. This was a retrospective analysis of 417 high-risk patients with > or =1 year of follow-up laboratory data. Analysis included changes in total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), non-HDL, triglycerides, and total cholesterol to HDL ratio; lipoprotein goal achievement; Framingham risk score; liver function; and cardiovascular events. At baseline, 66% of patients had coronary heart disease (CHD) or equivalent risk, 45% were not receiving dyslipidemia therapy, and 29% were on statin monotherapy. After 3 years in the program, 56% were receiving combination therapy, 41% were on monotherapy, and 2% were not on therapy. The 3 most common treatment regimens were statin plus niacin (36%), statin alone (22%), and niacin alone (14%). All lipoproteins improved from baseline (p <0.001). Overall, 62% to 74% of patients reached singular lipid goals and 35% achieved combined lipid goals. Patients with Framingham 10-year CHD risk of >20% were reduced from 6% to <1%. Only 29 patients (7.0%) had a cardiovascular event, including 5 (1.0%) who experienced a myocardial infarction. Aspartate aminotransferase/alanine transferase elevation >3 times normal occurred in 1% of patients. In conclusion, a collaborative-care practice model adopting individualized, aggressive pharmacologic and nonpharmacologic treatment strategies is highly effective in achieving lipid goals, is sustainable, and is safe. Furthermore, this approach yields reduced projected 10-year CHD risk. A low rate of cardiovascular events was observed.
[Drug-Disease]: niacin - dyslipidemia
[Title]: [High dose ara-C therapy induced bradycardia in an acute myeloid leukemia patient with inv (16)(p13q22)].
[Abstract]: A 20-year-old Japanese woman was diagnosed as having acute myeloid leukemia with inv(16)(p13 q22). She achieved complete remission (CR) after treatment with a standard dose of cytarabine(ara-C) and idarubicin. She received high dose ara-C and etoposide for the 2nd consolidation chemotherapy. On the 5th fraction of high dose ara-C, her heart rate dropped to 52/minute and returned to 72/minute after the cessation of ara-C. After achieving informed consent, we gave her another course of high dose ara-C, which once again resulted in a decreased heart rate. This suggests that the administration of high dose ara-C could cause bradycardia.
[Drug-Disease]: ara-C - acute myeloid leukemia
[Title]: [High dose ara-C therapy induced bradycardia in an acute myeloid leukemia patient with inv (16)(p13q22)].
[Abstract]: A 20-year-old Japanese woman was diagnosed as having acute myeloid leukemia with inv(16)(p13 q22). She achieved complete remission (CR) after treatment with a standard dose of cytarabine(ara-C) and idarubicin. She received high dose ara-C and etoposide for the 2nd consolidation chemotherapy. On the 5th fraction of high dose ara-C, her heart rate dropped to 52/minute and returned to 72/minute after the cessation of ara-C. After achieving informed consent, we gave her another course of high dose ara-C, which once again resulted in a decreased heart rate. This suggests that the administration of high dose ara-C could cause bradycardia.
[Drug-Disease]: etoposide - acute myeloid leukemia
[Title]: [High dose ara-C therapy induced bradycardia in an acute myeloid leukemia patient with inv (16)(p13q22)].
[Abstract]: A 20-year-old Japanese woman was diagnosed as having acute myeloid leukemia with inv(16)(p13 q22). She achieved complete remission (CR) after treatment with a standard dose of cytarabine(ara-C) and idarubicin. She received high dose ara-C and etoposide for the 2nd consolidation chemotherapy. On the 5th fraction of high dose ara-C, her heart rate dropped to 52/minute and returned to 72/minute after the cessation of ara-C. After achieving informed consent, we gave her another course of high dose ara-C, which once again resulted in a decreased heart rate. This suggests that the administration of high dose ara-C could cause bradycardia.
[Drug-Disease]: idarubicin - acute myeloid leukemia
[Title]: [The results of a clinical trial of the new drug agent carbabenzpyride].
[Abstract]: Analyzed were results of a clinical use of a new drug carbabanzpyrid in 57 patients as an analgetic, antipyretic, anti-inflammatory, interferonogenic drug. The drug proved effective in the complex treatment of several diseases, accompanied by fever, pain syndromes of different genesis and location, acute respiratory viral infections, active inflammatory processes of different etiology including bronchitis, pneumonia, active rheumatism, arthralgias, myalgias. The drug was of little efficacy in infections-allergic polyarthritis with a marked exudative component.
[Drug-Disease]: carbabenzpyride - fever
[Title]: [The results of a clinical trial of the new drug agent carbabenzpyride].
[Abstract]: Analyzed were results of a clinical use of a new drug carbabanzpyrid in 57 patients as an analgetic, antipyretic, anti-inflammatory, interferonogenic drug. The drug proved effective in the complex treatment of several diseases, accompanied by fever, pain syndromes of different genesis and location, acute respiratory viral infections, active inflammatory processes of different etiology including bronchitis, pneumonia, active rheumatism, arthralgias, myalgias. The drug was of little efficacy in infections-allergic polyarthritis with a marked exudative component.
[Drug-Disease]: carbabenzpyride - pain
[Title]: [Long lasting normalization of uric acid after combination therapy with 300 mg allopurinol and 60 mg benzbromarone in patients with gout and hyperuricemia].
[Abstract]: Lasting normalisation of uric acid levels after treatment of patients with gout and hyperuricaemia with a combination of 300 mg allopurinol and 60 mg benzbromarone A total of 210 patients (163 men, 47 women) with gout and hyperuricaemia was treated for three months with daily doses of 300 mg allopurinol and 60 mg benzbromarone. During the course of treatment, the uric acid levels decreased to 4.3 +/- 1.3 mg/dl in male, and 4.4 +/- 1.3 mg/dl in female patients. Both of these levels differ significantly from the initial levels (p less than 0.001). Three months after discontinuation of treatment, uric acid levels were 5.7 +/- 1.2 mg/dl in women, and 5.9 +/- 1.4 mg/dl in men, levels that again differed significantly from the initial levels (p less than 0.001); both levels were, however, within the therapeutic range of below 6.4 mg/dl.
[Drug-Disease]: allopurinol - gout and hyperuricaemia
[Title]: [Long lasting normalization of uric acid after combination therapy with 300 mg allopurinol and 60 mg benzbromarone in patients with gout and hyperuricemia].
[Abstract]: Lasting normalisation of uric acid levels after treatment of patients with gout and hyperuricaemia with a combination of 300 mg allopurinol and 60 mg benzbromarone A total of 210 patients (163 men, 47 women) with gout and hyperuricaemia was treated for three months with daily doses of 300 mg allopurinol and 60 mg benzbromarone. During the course of treatment, the uric acid levels decreased to 4.3 +/- 1.3 mg/dl in male, and 4.4 +/- 1.3 mg/dl in female patients. Both of these levels differ significantly from the initial levels (p less than 0.001). Three months after discontinuation of treatment, uric acid levels were 5.7 +/- 1.2 mg/dl in women, and 5.9 +/- 1.4 mg/dl in men, levels that again differed significantly from the initial levels (p less than 0.001); both levels were, however, within the therapeutic range of below 6.4 mg/dl.
[Drug-Disease]: allopurinol - hyperuricemia
[Title]: [Long lasting normalization of uric acid after combination therapy with 300 mg allopurinol and 60 mg benzbromarone in patients with gout and hyperuricemia].
[Abstract]: Lasting normalisation of uric acid levels after treatment of patients with gout and hyperuricaemia with a combination of 300 mg allopurinol and 60 mg benzbromarone A total of 210 patients (163 men, 47 women) with gout and hyperuricaemia was treated for three months with daily doses of 300 mg allopurinol and 60 mg benzbromarone. During the course of treatment, the uric acid levels decreased to 4.3 +/- 1.3 mg/dl in male, and 4.4 +/- 1.3 mg/dl in female patients. Both of these levels differ significantly from the initial levels (p less than 0.001). Three months after discontinuation of treatment, uric acid levels were 5.7 +/- 1.2 mg/dl in women, and 5.9 +/- 1.4 mg/dl in men, levels that again differed significantly from the initial levels (p less than 0.001); both levels were, however, within the therapeutic range of below 6.4 mg/dl.
[Drug-Disease]: benzbromarone - gout and hyperuricaemia
[Title]: [Long lasting normalization of uric acid after combination therapy with 300 mg allopurinol and 60 mg benzbromarone in patients with gout and hyperuricemia].
[Abstract]: Lasting normalisation of uric acid levels after treatment of patients with gout and hyperuricaemia with a combination of 300 mg allopurinol and 60 mg benzbromarone A total of 210 patients (163 men, 47 women) with gout and hyperuricaemia was treated for three months with daily doses of 300 mg allopurinol and 60 mg benzbromarone. During the course of treatment, the uric acid levels decreased to 4.3 +/- 1.3 mg/dl in male, and 4.4 +/- 1.3 mg/dl in female patients. Both of these levels differ significantly from the initial levels (p less than 0.001). Three months after discontinuation of treatment, uric acid levels were 5.7 +/- 1.2 mg/dl in women, and 5.9 +/- 1.4 mg/dl in men, levels that again differed significantly from the initial levels (p less than 0.001); both levels were, however, within the therapeutic range of below 6.4 mg/dl.
[Drug-Disease]: benzbromarone - hyperuricemia
[Title]: Low-dose azathioprine is effective and safe for maintenance of remission in patients with ulcerative colitis.
[Abstract]: BACKGROUND: 6-Mercaptopurine (6-MP) and azathioprine (AZA) have been used in patients with Crohn's disease (CD) and ulcerative colitis (UC) for reducing the dose of steroids and maintaining remission. However, some patients treated with 6-MP/AZA develop bone marrow suppression, one of the most serious side effects. The aim of this study was to evaluate the efficacy and safety of low-dose AZA (0.6-1.2 mg/kg per day) for maintaining remission in patients with UC. We also investigated the relationship between bone marrow suppression and thiopurine methyltransferase ( TPMT) mutation in the Japanese population. METHODS: Study 1. To investigate the frequency of TPMT mutation, findings for 82 patients among 141 patients with UC or CD who were treated with AZA or 6-MP were analyzed retrospectively. Polymerase chain reaction (PCR) methods were used to analyze allele mutations of the TPMT gene. Study 2. A multicenter prospective trial was performed. The subjects were 22 patients with UC with presence of remission for 3 months or more. They were treated with 50 mg/day of AZA, and we evaluated the remission rate at 6 months, adverse side effects, and changes in prednisone doses after the initiation of AZA. RESULTS: Study 1. Seventy-four (91%) of the 82 patients analyzed had no TPMT mutation, 7 (8%) had one mutant allele, and 1 (1%) had two mutant alleles. Of the total of 141 patients, 4 (44%) of the 9 patients who were treated with 50 mg/day of 6-MP or 100 mg/day of AZA developed bone marrow suppression, although no mutation of TPMT was seen in any of these patients. On the other hand, 8 (6%) of the 132 patients who were treated with 30 mg/day of 6-MP or 50 mg/day of AZA developed bone marrow suppression. Seven of 8 patients (88%) who developed bone marrow suppression with a low dose of AZA had a mutant TPMT allele. Study 2. In the 17 patients who could continue taking low-dose AZA for 6 months, 15 (88%) maintained remission. Of 8 patients treated with low-dose prednisone (5-10 mg/day), 3 patients (38%) could discontinue oral prednisone and 4 (50%) could reduce its dose. Six of the 22 patients (27%) had some adverse side effects. These side effects were ameliorated, or disappeared spontaneously, or disappeared with the discontinuation of AZA. CONCLUSIONS: A dose of 50 mg/day of AZA is effective and safe for maintenance of remission in the Japanese population. Investigation of the TPMT allele may be useful for predicting the appearance of bone marrow suppression, when low-dose 6-MP or AZA is given.
[Drug-Disease]: AZA - ulcerative colitis
[Title]: Low-dose azathioprine is effective and safe for maintenance of remission in patients with ulcerative colitis.
[Abstract]: BACKGROUND: 6-Mercaptopurine (6-MP) and azathioprine (AZA) have been used in patients with Crohn's disease (CD) and ulcerative colitis (UC) for reducing the dose of steroids and maintaining remission. However, some patients treated with 6-MP/AZA develop bone marrow suppression, one of the most serious side effects. The aim of this study was to evaluate the efficacy and safety of low-dose AZA (0.6-1.2 mg/kg per day) for maintaining remission in patients with UC. We also investigated the relationship between bone marrow suppression and thiopurine methyltransferase ( TPMT) mutation in the Japanese population. METHODS: Study 1. To investigate the frequency of TPMT mutation, findings for 82 patients among 141 patients with UC or CD who were treated with AZA or 6-MP were analyzed retrospectively. Polymerase chain reaction (PCR) methods were used to analyze allele mutations of the TPMT gene. Study 2. A multicenter prospective trial was performed. The subjects were 22 patients with UC with presence of remission for 3 months or more. They were treated with 50 mg/day of AZA, and we evaluated the remission rate at 6 months, adverse side effects, and changes in prednisone doses after the initiation of AZA. RESULTS: Study 1. Seventy-four (91%) of the 82 patients analyzed had no TPMT mutation, 7 (8%) had one mutant allele, and 1 (1%) had two mutant alleles. Of the total of 141 patients, 4 (44%) of the 9 patients who were treated with 50 mg/day of 6-MP or 100 mg/day of AZA developed bone marrow suppression, although no mutation of TPMT was seen in any of these patients. On the other hand, 8 (6%) of the 132 patients who were treated with 30 mg/day of 6-MP or 50 mg/day of AZA developed bone marrow suppression. Seven of 8 patients (88%) who developed bone marrow suppression with a low dose of AZA had a mutant TPMT allele. Study 2. In the 17 patients who could continue taking low-dose AZA for 6 months, 15 (88%) maintained remission. Of 8 patients treated with low-dose prednisone (5-10 mg/day), 3 patients (38%) could discontinue oral prednisone and 4 (50%) could reduce its dose. Six of the 22 patients (27%) had some adverse side effects. These side effects were ameliorated, or disappeared spontaneously, or disappeared with the discontinuation of AZA. CONCLUSIONS: A dose of 50 mg/day of AZA is effective and safe for maintenance of remission in the Japanese population. Investigation of the TPMT allele may be useful for predicting the appearance of bone marrow suppression, when low-dose 6-MP or AZA is given.
[Drug-Disease]: AZA - Crohn's disease