B1tta/Drug-ACE huggingface dataset:
[Title]: The effect of amiloride on amphotericin B-induced hypokalaemia.
[Abstract]: Amiloride was administered to 19 oncology patients exhibiting marked amphotericin B-induced electrolyte wasting. Mean serum potassium concentrations increased in the 5 days preceding and following administration (3.4 +/- 0.5 versus 3.9 +/- 0.8 mmol/L, P = 0.002). A trend towards decreased potassium supplementation was also observed (48.0 +/- 66.5 versus 29.4 +/- 43.2 mmol/day, P = 0.12). Amiloride is a therapeutic option to decrease potassium wasting in patients being treated with amphotericin B.
[Drug-Disease]: Amiloride - hypokalaemia
[Title]: Efficacy of metrifonate in improving the psychiatric and behavioral disturbances of patients with Alzheimer's disease.
[Abstract]: Neuropsychiatric and behavioral symptoms are frequent and problematic components of Alzheimer's disease (AD). In two previously reported studies, metrifonate was shown to benefit behavioral symptoms as assessed by the Neuropsychiatric Inventory (NPI). In this post hoc analysis, detailed studies were completed to determine the effects of metrifonate on individual symptoms. This study was a retrospective analysis of pooled NPI data from two double-blind, placebo-controlled, multicenter 26-week studies of metrifonate that had achieved similar levels of cholinesterase inhibition. Mild-to-moderate probable AD patients received placebo (n = 222) or metrifonate (n = 450) 30 to 60 mg by weight or a 50-mg fixed dose once daily. At 26 weeks, metrifonate-treated patients had significantly reduced NPI total scores (P = .001) and fewer neuropsychiatric symptoms when compared with placebo-treated patients, including hallucinations (P = .004), agitation/aggression (P = .006), depression/dysphoria (P = .011), apathy (P = .019), and aberrant motor behavior (P = .008). Metrifonate reduced or stabilized neuropsychiatric disturbances in 60% of symptomatic patients. Almost 40% of metrifonate-treated patients had a clinically relevant reduction (> or = 30% decrease in NPI score) in their neuropsychiatric disturbances (P = .002). High proportions of metrifonate-treated patients manifested clinically relevant reductions in anxiety (58%, P = .009), apathy (51%, P = .020), and depression/dysphoria (50%, P = .021) compared to placebo. The metrifonate-associated reductions in NPI scores were evident by week 12 and were maintained for the 26-week study period. There was an overall effect size of metrifonate of approximately 15% on total NPI scores when compared to placebo. Metrifonate significantly reduced many of the psychiatric and behavioral symptoms of AD. The observations suggest that enhancement of cholinergic functions in AD has beneficial effects on behavior.
[Drug-Disease]: Metrifonate - AD
[Title]: Long-term asthma control with oral montelukast and inhaled beclomethasone for adults and children 6 years and older.
[Abstract]: BACKGROUND: Leukotriene receptor antagonists have demonstrated clinical benefits in chronic asthma studies of up to 3 months in duration. The effects of these agents over extended periods of time have not been reported. OBJECTIVE: To describe the long-term effect of oral montelukast, a potent and specific cysteinyl leukotriene receptor antagonist, compared with inhaled corticosteroids in both adult and paediatric patients with chronic asthma. METHODS: Male and female patients with chronic, stable asthma (adults aged 15-85 years, children aged 6-14 years), who had completed double-blind, placebo-controlled clinical studies, participated in three extension studies with oral montelukast taken once daily (10 mg tablet for adults, 5 mg chewable tablet for paediatric patients) or inhaled corticosteroids (beclomethasone 200 microg twice daily for adults, beclomethasone 100 microg or equivalent three times daily for children). A double-blind adult extension study was 37 weeks in duration; open-label adult extension studies were 156 (adults) and 112 (paediatric) weeks in duration. A total of 436, 374, and 245 patients entered these extension studies, respectively. RESULTS: Treatment with both montelukast and inhaled corticosteroids resulted in improvement in multiple parameters of asthma control. Improvements in daytime symptom scores were generally comparable among treatment groups. No tachyphylaxis to the effects of montelukast was evident. In the adult open-label study, however, the effect of beclomethasone on mean forced expiratory volume in 1 second (FEV1) gradually decreased from start of the study to the end of the follow-up treatment period. CONCLUSION: Both montelukast and inhaled corticosteroids were effective in controlling mild to moderate chronic asthma; the relative effectiveness of montelukast and beclomethasone were similar in open-label conditions. The hypothesis, that clinical practice conditions (e.g., adherence) may have a significant impact on the effectiveness of these therapies, should be tested in future clinical trials.
[Drug-Disease]: montelukast - chronic asthma
[Title]: Long-term asthma control with oral montelukast and inhaled beclomethasone for adults and children 6 years and older.
[Abstract]: BACKGROUND: Leukotriene receptor antagonists have demonstrated clinical benefits in chronic asthma studies of up to 3 months in duration. The effects of these agents over extended periods of time have not been reported. OBJECTIVE: To describe the long-term effect of oral montelukast, a potent and specific cysteinyl leukotriene receptor antagonist, compared with inhaled corticosteroids in both adult and paediatric patients with chronic asthma. METHODS: Male and female patients with chronic, stable asthma (adults aged 15-85 years, children aged 6-14 years), who had completed double-blind, placebo-controlled clinical studies, participated in three extension studies with oral montelukast taken once daily (10 mg tablet for adults, 5 mg chewable tablet for paediatric patients) or inhaled corticosteroids (beclomethasone 200 microg twice daily for adults, beclomethasone 100 microg or equivalent three times daily for children). A double-blind adult extension study was 37 weeks in duration; open-label adult extension studies were 156 (adults) and 112 (paediatric) weeks in duration. A total of 436, 374, and 245 patients entered these extension studies, respectively. RESULTS: Treatment with both montelukast and inhaled corticosteroids resulted in improvement in multiple parameters of asthma control. Improvements in daytime symptom scores were generally comparable among treatment groups. No tachyphylaxis to the effects of montelukast was evident. In the adult open-label study, however, the effect of beclomethasone on mean forced expiratory volume in 1 second (FEV1) gradually decreased from start of the study to the end of the follow-up treatment period. CONCLUSION: Both montelukast and inhaled corticosteroids were effective in controlling mild to moderate chronic asthma; the relative effectiveness of montelukast and beclomethasone were similar in open-label conditions. The hypothesis, that clinical practice conditions (e.g., adherence) may have a significant impact on the effectiveness of these therapies, should be tested in future clinical trials.
[Drug-Disease]: beclomethasone - chronic asthma
[Title]: Hydroxyurea in stage D carcinoma of the prostate: a pilot study.
[Abstract]: There was 13 patinets with histologically metastatic prostatic adenocarcinoma treated with a single oral dose of 80 mg. per kg. hydroxyurea every third day (based on ideal or actual weight, whichever is less) and 12.5 mg. chlorotrianisene per day. Toxicity was mild. The most common manifestations were nausea, occasional vomiting leukopenia. A definite attempt was made to depress the white blood count to approximately 2,000 cells per cu. mm. Hydroxyurea was not discontinued unless the white blood count decreased to less that 2,000 cells per cu. mm., after which a single dose was usually omitted. Omission of a single dose would allow the white blood count to return promptly to more than 2,000 cells per cu. mm. Objective tumor regression was demonstrated in 6 of the 13 patients and all patients had a definite improvement in the quality of life.
[Drug-Disease]: chlorotrianisene - prostatic adenocarcinoma
[Title]: Hydroxyurea in stage D carcinoma of the prostate: a pilot study.
[Abstract]: There was 13 patinets with histologically metastatic prostatic adenocarcinoma treated with a single oral dose of 80 mg. per kg. hydroxyurea every third day (based on ideal or actual weight, whichever is less) and 12.5 mg. chlorotrianisene per day. Toxicity was mild. The most common manifestations were nausea, occasional vomiting leukopenia. A definite attempt was made to depress the white blood count to approximately 2,000 cells per cu. mm. Hydroxyurea was not discontinued unless the white blood count decreased to less that 2,000 cells per cu. mm., after which a single dose was usually omitted. Omission of a single dose would allow the white blood count to return promptly to more than 2,000 cells per cu. mm. Objective tumor regression was demonstrated in 6 of the 13 patients and all patients had a definite improvement in the quality of life.
[Drug-Disease]: Hydroxyurea - prostatic adenocarcinoma
[Title]: A randomized, double-blind, placebo-controlled trial of supplementary vitamins E, C and their combination for treatment of haemodialysis cramps.
[Abstract]: BACKGROUND: Muscle cramps that improve after carnitine or vitamin E therapies are common in haemodialysis (HD) patients. Because vitamin C participates in carnitine biosynthesis, and its levels are reduced in uraemia, subclinical vitamin C depletion may contribute to HD cramps. Our aim was to determine the effects of vitamins C, E and their combination on the frequency and intensity of HD cramps. METHODS: In this placebo-controlled, double-blind study, 60 HD-patients were randomized into four therapeutic groups. Each group (n=15) received six identical capsules daily for 8 weeks, containing one of the following: vitamin E (400 mg), vitamin C (250 mg), their combination, or placebo. RESULTS: The frequency and intensity of HD cramps decreased significantly in all three vitamin groups compared with the placebo group at the end of the trial, and compared with the pre-treatment values. At the end of the trial, vitamins E, C, their combination, and placebo produced cramp reductions of 54, 61, 97 and 7%, respectively. The percentage cramp reduction had no significant correlation with age, sex, aetiology of end-stage renal disease, serum electrolytes or HD duration, but showed a positive correlation (r=0.33, P=0.01) with the type of therapy. No vitamin-related adverse effects were encountered during the trial. CONCLUSION: Short-term treatment with the combination of vitamins E and C is safe and effective in reducing HD cramps; however, its safety for prolonged therapy has yet to be evaluated in HD patients.
[Drug-Disease]: vitamin C - Muscle cramps
[Title]: A randomized, double-blind, placebo-controlled trial of supplementary vitamins E, C and their combination for treatment of haemodialysis cramps.
[Abstract]: BACKGROUND: Muscle cramps that improve after carnitine or vitamin E therapies are common in haemodialysis (HD) patients. Because vitamin C participates in carnitine biosynthesis, and its levels are reduced in uraemia, subclinical vitamin C depletion may contribute to HD cramps. Our aim was to determine the effects of vitamins C, E and their combination on the frequency and intensity of HD cramps. METHODS: In this placebo-controlled, double-blind study, 60 HD-patients were randomized into four therapeutic groups. Each group (n=15) received six identical capsules daily for 8 weeks, containing one of the following: vitamin E (400 mg), vitamin C (250 mg), their combination, or placebo. RESULTS: The frequency and intensity of HD cramps decreased significantly in all three vitamin groups compared with the placebo group at the end of the trial, and compared with the pre-treatment values. At the end of the trial, vitamins E, C, their combination, and placebo produced cramp reductions of 54, 61, 97 and 7%, respectively. The percentage cramp reduction had no significant correlation with age, sex, aetiology of end-stage renal disease, serum electrolytes or HD duration, but showed a positive correlation (r=0.33, P=0.01) with the type of therapy. No vitamin-related adverse effects were encountered during the trial. CONCLUSION: Short-term treatment with the combination of vitamins E and C is safe and effective in reducing HD cramps; however, its safety for prolonged therapy has yet to be evaluated in HD patients.
[Drug-Disease]: vitamin E - Muscle cramps
[Title]: Famciclovir treatment of hepatitis B infection following liver transplantation: a long-term, multi-centre study.
[Abstract]: Famciclovir is a novel guanosine nucleoside analogue with activity against herpes viruses and hepatitis B virus (HBV). Several preliminary reports have described efficacy of famciclovir in patients with recurrent hepatitis B after orthotopic liver transplantation (OLT). This report describes the largest study to date of long-term famciclovir treatment in patients with de novo or recurrent hepatitis B post-OLT. One hundred thirty patients with detectable serum HBV DNA after OLT received oral famciclovir 500 mg tid on a compassionate-use basis. Safety analyses included all treated patients; efficacy was assessed in all patients and a subgroup of 73 patients with complete baseline HBV DNA and alanine aminotransferase (ALT) data who had received > or =6 months of treatment. Efficacy parameters included serum levels of HBV DNA, ALT, and anti-HBe or anti-HBs seroconversion rates. Of the 70 patients treated for > or =6 months who could be evaluated for response/non-response to famciclovir, 52 (74%) were responders, defined as patients who experienced a 70% decrease or more in HBV DNA levels from baseline, or who became HBV DNA-negative, for at least two consecutive visits. In famciclovir responders, HBV DNA levels decreased by a median of 91% after 12 weeks of treatment, 95% after 6 months and >99% after 18 months of treatment. Marked differentiation between responders and non-responders could be made soon after the onset of treatment. Among anti-HBe positive patients with evidence of HBV replication, 12/13 were responders. Patients with high baseline ALT levels experienced more rapid suppression of HBV DNA during therapy with famciclovir. Famciclovir therapy was safe and well tolerated; serious adverse events were reported infrequently. Famciclovir treatment may be beneficial in patients with hepatitis B infection post-OLT.
[Drug-Disease]: Famciclovir - hepatitis B infection
[Title]: Synergistic antiallergic activity of combined histamine H1- and cysteinyl leukotriene1-receptor blockade in human bronchus.
[Abstract]: Mast cell histamine (HA) and cysteinyl leukotrienes (CysLT) account for most of the early phase bronchospasm in asthma. However, activation of the smooth muscle CysLT1-receptor plays a major role in asthmatic bronchospasms. CysLT-receptor antagonists or CysLT-synthesis inhibitors are efficacious in asthma but do not completely abolish asthmatic bronchospasms. A recent clinical study showed that combined antagonists loratadine (H1) and zafirlukast (CysLT1) were more effective against allergic bronchospasms than either drug alone. We examined the combined efficacy of H1- and CysLT1-receptor antagonists in allergic human bronchus. The H1- and CysLT1-receptor antagonists chlorpheniramine (CTM; 1 microM) and MK-571 (0.03 microM), were tested alone and in combination, against anti-human IgE antibody (Ab)-induced contractions of passively sensitized isolated human bronchus. Ab-induced allergic contractions were reduced 15% and 36% by CTM (1 microM) and MK-571 (0.03 microM), respectively. Combined CTM (1 microM) and MK-571 (0.03 microM) significantly inhibited the Ab response by 87%. Mechanistic investigations in isolated human bronchus and cultured human cord blood mast cells suggest that H1- and CysLT-receptor interactions likely occur at the airway smooth muscle level. CTM and MK-571 synergistically inhibited human allergic bronchospasm in the present in vitro model. The mechanism underlying this synergistic activity requires further investigation.
[Drug-Disease]: MK-571 - asthmatic bronchospasms
[Title]: Synergistic antiallergic activity of combined histamine H1- and cysteinyl leukotriene1-receptor blockade in human bronchus.
[Abstract]: Mast cell histamine (HA) and cysteinyl leukotrienes (CysLT) account for most of the early phase bronchospasm in asthma. However, activation of the smooth muscle CysLT1-receptor plays a major role in asthmatic bronchospasms. CysLT-receptor antagonists or CysLT-synthesis inhibitors are efficacious in asthma but do not completely abolish asthmatic bronchospasms. A recent clinical study showed that combined antagonists loratadine (H1) and zafirlukast (CysLT1) were more effective against allergic bronchospasms than either drug alone. We examined the combined efficacy of H1- and CysLT1-receptor antagonists in allergic human bronchus. The H1- and CysLT1-receptor antagonists chlorpheniramine (CTM; 1 microM) and MK-571 (0.03 microM), were tested alone and in combination, against anti-human IgE antibody (Ab)-induced contractions of passively sensitized isolated human bronchus. Ab-induced allergic contractions were reduced 15% and 36% by CTM (1 microM) and MK-571 (0.03 microM), respectively. Combined CTM (1 microM) and MK-571 (0.03 microM) significantly inhibited the Ab response by 87%. Mechanistic investigations in isolated human bronchus and cultured human cord blood mast cells suggest that H1- and CysLT-receptor interactions likely occur at the airway smooth muscle level. CTM and MK-571 synergistically inhibited human allergic bronchospasm in the present in vitro model. The mechanism underlying this synergistic activity requires further investigation.
[Drug-Disease]: chlorpheniramine - asthmatic bronchospasms
[Title]: Phase I study of a weekly schedule of oxaliplatin, high-dose leucovorin, and infusional fluorouracil in pretreated patients with advanced colorectal cancer.
[Abstract]: PURPOSE: To identify the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of oxaliplatin (L-OHP) given on a weekly schedule including fixed doses of leucovorin (LV) and infusional 5-fluorouracil (5-FU), to define the toxicity profile of this regimen and to find preliminary evidence of its activity in pretreated patients with metastatic colorectal cancer (MCRC). PATIENTS AND METHODS: Twenty-one patients with progressive disease, treated with fluoropyrimidines and with histologically measurable MCRC entered into this phase I study. Fixed doses of LV (500 mg/m2) followed by a 48-hour 5-FU 2600 mg/m2 infusion (5-FU48h) were administered with escalating doses of L-OHP, starting from 60 mg/m2 and with stepwise increments of 5 mg/m2. No intra-patient dose escalation was allowed. Treatment was given once a week for four consecutive weeks, followed by a one-week rest period. RESULTS: Three dose levels were tested. The MTD was L-OHP 70 mg/m2 since two of the three patients showed dose-limiting diarrhea and the third developed neutropenia during the first cycle of chemotherapy. Most patients complained of mild peripheral sensitive neurotoxicity, which was related to the cumulative dose of L-OHP. Treatment delays were necessary for a total of 42 cases, but only in II of 42 after the pre-arranged 10% dose reduction of 5-FU (2300 mg/m2). Sixteen patients were evaluable for response: seven (33%; 95% confidence interval (CI): 14.6%-57.0%) were considered to show a major response (one complete), six showed a stable disease, and in addition progressive disease was observed in three patients. CONCLUSIONS: Our results show that L-OHP, LV and 5-FU can be administered safely and repetitively using a weekly schedule. Diarrhea and neutropenia are the DLT of this regimen. Its activity and its manageable toxicity profile deserve further evaluation in chemotherapy-naive MCRC patients. The doses recommended for phase II trials are: L-OHP 65 mg/m2, LV 500 mg/m2 and 5-FU48h 2300 mg/m2 infusion given on a weekly-times-four schedule followed by a one-week rest period.
[Drug-Disease]: L-OHP - colorectal cancer
[Title]: Phase I study of a weekly schedule of oxaliplatin, high-dose leucovorin, and infusional fluorouracil in pretreated patients with advanced colorectal cancer.
[Abstract]: PURPOSE: To identify the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of oxaliplatin (L-OHP) given on a weekly schedule including fixed doses of leucovorin (LV) and infusional 5-fluorouracil (5-FU), to define the toxicity profile of this regimen and to find preliminary evidence of its activity in pretreated patients with metastatic colorectal cancer (MCRC). PATIENTS AND METHODS: Twenty-one patients with progressive disease, treated with fluoropyrimidines and with histologically measurable MCRC entered into this phase I study. Fixed doses of LV (500 mg/m2) followed by a 48-hour 5-FU 2600 mg/m2 infusion (5-FU48h) were administered with escalating doses of L-OHP, starting from 60 mg/m2 and with stepwise increments of 5 mg/m2. No intra-patient dose escalation was allowed. Treatment was given once a week for four consecutive weeks, followed by a one-week rest period. RESULTS: Three dose levels were tested. The MTD was L-OHP 70 mg/m2 since two of the three patients showed dose-limiting diarrhea and the third developed neutropenia during the first cycle of chemotherapy. Most patients complained of mild peripheral sensitive neurotoxicity, which was related to the cumulative dose of L-OHP. Treatment delays were necessary for a total of 42 cases, but only in II of 42 after the pre-arranged 10% dose reduction of 5-FU (2300 mg/m2). Sixteen patients were evaluable for response: seven (33%; 95% confidence interval (CI): 14.6%-57.0%) were considered to show a major response (one complete), six showed a stable disease, and in addition progressive disease was observed in three patients. CONCLUSIONS: Our results show that L-OHP, LV and 5-FU can be administered safely and repetitively using a weekly schedule. Diarrhea and neutropenia are the DLT of this regimen. Its activity and its manageable toxicity profile deserve further evaluation in chemotherapy-naive MCRC patients. The doses recommended for phase II trials are: L-OHP 65 mg/m2, LV 500 mg/m2 and 5-FU48h 2300 mg/m2 infusion given on a weekly-times-four schedule followed by a one-week rest period.
[Drug-Disease]: LV - colorectal cancer